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Christian Seiler


michael.stoller@insel.ch

Journal articles

2012
Pascal Meier, Harry Hemingway, Alexandra J Lansky, Guido Knapp, Bertram Pitt, Christian Seiler (2012)  The impact of the coronary collateral circulation on mortality: a meta-analysis.   Eur Heart J 33: 5. 614-621 Mar  
Abstract: The coronary collateral circulation as an alternative source of blood supply has shown benefits regarding several clinical endpoints in patients with myocardial infarction (MI) such as infarct size and left ventricular remodelling. However, its impact on hard endpoints such as mortality and its impact in patients with stable coronary artery disease (CAD) is more controversial. The purpose of this systematic review and meta-analysis was to explore the impact of collateral circulation on all-cause mortality.
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Valérie Stolt, Stéphane Cook, Lorenz Räber, Sunil Wani, Ali Garachamani, Rolf Vogel, Christian Seiler, Stephan Windecker, Bernhard Meier (2012)  Amplatzer Septal Occluder to treat iatrogenic cardiac perforations.   Catheter Cardiovasc Interv 79: 2. 263-270 Feb  
Abstract: Iatrogenic free wall cardiac perforation is a rare but serious complication encountered during percutaneous cardiac procedures, which usually leads to tamponade and death. Septal occluder devices have been developed for sealing intracardiac shunts but may be also used in this emergency setting.
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2011
Tobias Rutz, Steffen Gloekler, Stefano F de Marchi, Tobias Traupe, Pascal Meier, Parham Eshtehardi, Stéphane Cook, Rolf Vogel, Paul Mohacsi, Christian Seiler (2011)  Coronary collateral function in the transplanted heart: propensity score matching with coronary artery disease.   Heart 97: 7. 557-563 Apr  
Abstract: The function of the coronary collateral circulation in heart transplant patients has not been investigated in a controlled fashion. Since it partly belongs to the microcirculation, which is affected by transplant vasculopathy, the hypothesis was tested that the coronary collateral circulation in heart transplant recipients is less developed than in coronary artery disease (CAD) patients.
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Andreas Indermühle, Rolf Vogel, Pascal Meier, Rainer Zbinden, Christian Seiler (2011)  Myocardial blood volume and coronary resistance during and after coronary angioplasty.   Am J Physiol Heart Circ Physiol 300: 3. H1119-H1124 Mar  
Abstract: Animal experiments have shown that the coronary circulation is pressure distensible, i.e., myocardial blood volume (MBV) increases with perfusion pressure. In humans, however, corresponding measurements are lacking so far. We sought to quantify parameters reflecting coronary distensibility such as MBV and coronary resistance (CR) during and after coronary angioplasty. Thirty patients with stable coronary artery disease underwent simultaneous coronary perfusion pressure assessment and myocardial contrast echocardiography (MCE) of 37 coronary arteries and their territories during and after angioplasty. MCE yielded MBV and myocardial blood flow (MBF; in ml · min(-1) · g(-1)). Complete data sets were obtained in 32 coronary arteries and their territories from 26 patients. During angioplasty, perfusion pressure, i.e., coronary occlusive pressure, and MBV varied between 9 and 57 mmHg (26.9 ± 11.9 mmHg) and between 1.2 and 14.5 ml/100 g (6.7 ± 3.7 ml/100 g), respectively. After successful angioplasty, perfusion pressure and MBV increased significantly (P < 0.001 for both) and varied between 64 and 118 mmHg (93.5 ± 12.8 mmHg) and between 3.7 and 17.3 ml/100 g (9.8 ± 3.4 ml/100 g), respectively. Mean MBF increased from 31 ± 20 ml · min(-1) · g(-1) during coronary occlusion, reflecting collateral flow, to 121 ± 33 ml · min(-1) · g(-1) (P < 0.01), whereas mean CR, i.e., the ratio of perfusion pressure and MBF, decreased by 20% (P < 0.001). In conclusion, the human coronary circulation is pressure distensible. MCE allows for the quantification of CR and MBV in humans.
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Lorenz Räber, Peter Jüni, Eveline Nüesch, Bindu Kalesan, Peter Wenaweser, Aris Moschovitis, Ahmed A Khattab, Maryam Bahlo, Mario Togni, Stéphane Cook, Rolf Vogel, Christian Seiler, Bernhard Meier, Stephan Windecker (2011)  Long-term comparison of everolimus-eluting and sirolimus-eluting stents for coronary revascularization.   J Am Coll Cardiol 57: 21. 2143-2151 May  
Abstract: This study sought to compare the unrestricted use of everolimus-eluting stents (EES) with sirolimus-eluting stents (SES) in patients undergoing percutaneous coronary intervention.
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Stefano F de Marchi, Steffen Gloekler, Stefano F Rimoldi, Patrizia Rölli, Hélène Steck, Christian Seiler (2011)  Microvascular response to metabolic and pressure challenge in the human coronary circulation.   Am J Physiol Heart Circ Physiol 301: 2. H434-H441 Aug  
Abstract: In vivo observations of microcirculatory behavior during autoregulation and adaptation to varying myocardial oxygen demand are scarce in the human coronary system. This study assessed microvascular reactions to controlled metabolic and pressure provocation [bicycle exercise and external counterpulsation (ECP)]. In 20 healthy subjects, quantitative myocardial contrast echocardiography and arterial applanation tonometry were performed during increasing ECP levels, as well as before and during bicycle exercise. Myocardial blood flow (MBF; ml·min(-1)·g(-1)), the relative blood volume (rBV; ml/ml), the coronary vascular resistance index (CVRI; dyn·s·cm(-5)/g), the pressure-work index (PWI), and the pressure-rate product (mmHg/min) were assessed. MBF remained unchanged during ECP (1.08 ± 0.44 at baseline to 0.92 ± 0.38 at high-level ECP). Bicycle exercise led to an increase in MBF from 1.03 ± 0.39 to 3.42 ± 1.11 (P < 0.001). The rBV remained unchanged during ECP, whereas it increased under exercise from 0.13 ± 0.033 to 0.22 ± 0.07 (P < 0.001). The CVRI showed a marked increase under ECP from 7.40 ± 3.38 to 11.05 ± 5.43 and significantly dropped under exercise from 7.40 ± 2.78 to 2.21 ± 0.87 (both P < 0.001). There was a significant correlation between PWI and MBF in the pooled exercise data (slope: +0.162). During ECP, the relationship remained similar (slope: +0.153). Whereas physical exercise decreases coronary vascular resistance and induces considerable functional capillary recruitment, diastolic pressure transients up to 140 mmHg trigger arteriolar vasoconstriction, keeping MBF and functional capillary density constant. Demand-supply matching was maintained over the entire ECP pressure range.
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Michael Pavlicek, Andreas Wahl, Tobias Rutz, Stefano F de Marchi, Ron Hille, Kerstin Wustmann, Hélène Steck, Christina Eigenmann, Markus Schwerzmann, Christian Seiler (2011)  Right ventricular systolic function assessment: rank of echocardiographic methods vs. cardiac magnetic resonance imaging.   Eur J Echocardiogr 12: 11. 871-880 Nov  
Abstract: Right ventricular (RV) systolic function is prognostically important, but its assessment by echocardiography remains challenging, in part because of the multitude of available measurement methods. The purpose of this prospective study was to rank these methods against the reference of RV ejection fraction (EF) as obtained in a broad clinical population by magnetic resonance imaging (MRI).
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Stefano F de Marchi, Steffen Gloekler, Pascal Meier, Tobias Traupe, Hélène Steck, Stéphane Cook, Rolf Vogel, Christian Seiler (2011)  Determinants of preformed collateral vessels in the human heart without coronary artery disease.   Cardiology 118: 3. 198-206 06  
Abstract: Coronary collaterals protect myocardium jeopardized by coronary artery disease (CAD). Promotion of collateral circulation is desirable before myocardial damage occurs. Therefore, determinants of collateral preformation in patients without CAD should be elucidated.
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Lorenz Räber, Lea Wohlwend, Mathias Wigger, Mario Togni, Simon Wandel, Peter Wenaweser, Stéphane Cook, Aris Moschovitis, Rolf Vogel, Bindu Kalesan, Christian Seiler, Franz Eberli, Thomas F Lüscher, Bernhard Meier, Peter Jüni, Stephan Windecker (2011)  Five-year clinical and angiographic outcomes of a randomized comparison of sirolimus-eluting and paclitaxel-eluting stents: results of the Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization LATE trial.   Circulation 123: 24. 2819-28, 6 p following 2828 Jun  
Abstract: Long-term comparative data of first-generation drug-eluting stents are scarce. We investigated clinical and angiographic outcomes of sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) at 5 years as part of the Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization (SIRTAX) LATE study.
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Tobias Rutz, Steffen Gloekler, Stefano F de Marchi, Tobias Traupe, Pascal Meier, Parham Eshtehardi, Stephane Cook, Rolf Vogel, Paul Mohacsi, Christian Seiler (2011)  Coronary collateral function in the transplanted heart : propensity score matching with coronary artery disease   HEART 97: 7. 557-563 APR  
Abstract: Background The function of the coronary collateral circulation in heart transplant patients has not been investigated in a controlled fashion. Since it partly belongs to the microcirculation, which is affected by transplant vasculopathy, the hypothesis was tested that the coronary collateral circulation in heart transplant recipients is less developed than in coronary artery disease (CAD) patients. Methods 40 heart transplant patients underwent a total of 51 quantitative, coronary pressure-derived collateral measurements and intravascular ultrasound (IVUS). The collateral flow index (CFI) was calculated as mean coronary occlusive pressure divided by mean aortic pressure, both subtracted by central venous pressure. A propensity score matching for angiographic coronary stenosis severity, heart rate, the presence of arterial hypertension and dyslipidaemia was performed using CAD patients of the institutional CFI database (n = 1076) as the control group. Results Eighty per cent (32/40) of the heart transplant patients showed transplant vasculopathy as assessed by IVUS (intima thickness >= 0.5 mm). Without propensity score matching, CFI was equal to 0.152 +/- 0.102 in the heart transplant group (age 55614 years) and 0.189 +/- 0.134 in the entire CAD group (p = 0.054). After matching, CFI was 0.152 +/- 0.102 in the heart transplant group and 0.176 +/- 0.096 (p = 0.37) in the matched CAD group (age 63610 years). IVUS data were unrelated to CFI in the heart transplant group. Conclusions Heart transplant patients present with the same degree of functional collateral flow compared with a matched group of CAD patients.
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Andreas Indermuehle, Rolf Vogel, Pascal Meier, Rainer Zbinden, Christian Seiler (2011)  Myocardial blood volume and coronary resistance during and after coronary angioplasty   AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 300: 3. MAR  
Abstract: Indermuhle A, Vogel R, Meier P, Zbinden R, Seiler C. Myocardial blood volume and coronary resistance during and after coronary angioplasty. Am J Physiol Heart Circ Physiol 300: H1119-H1124, 2011. First published January 7, 2011; doi: 10.1152/ajpheart.01022.2010.-Animal experiments have shown that the coronary circulation is pressure distensible, i.e., myocardial blood volume (MBV) increases with perfusion pressure. In humans, however, corresponding measurements are lacking so far. We sought to quantify parameters reflecting coronary distensibility such as MBV and coronary resistance (CR) during and after coronary angioplasty. Thirty patients with stable coronary artery disease underwent simultaneous coronary perfusion pressure assessment and myocardial contrast echocardiography (MCE) of 37 coronary arteries and their territories during and after angioplasty. MCE yielded MBV and myocardial blood flow (MBF; in ml.min(-1).g(-1)). Complete data sets were obtained in 32 coronary arteries and their territories from 26 patients. During angioplasty, perfusion pressure, i.e., coronary occlusive pressure, and MBV varied between 9 and 57 mmHg (26.9 +/- 11.9 mmHg) and between 1.2 and 14.5 ml/100 g (6.7 +/- 3.7 ml/100 g), respectively. After successful angioplasty, perfusion pressure and MBV increased significantly (P < 0.001 for both) and varied between 64 and 118 mmHg (93.5 +/- 12.8 mmHg) and between 3.7 and 17.3 ml/100 g (9.8 +/- 3.4 ml/100 g), respectively. Mean MBF increased from 31 +/- 20 ml.min(-1).g(-1) during coronary occlusion, reflecting collateral flow, to 121 +/- 33 ml.min(-1).g(-1) (P < 0.01), whereas mean CR, i.e., the ratio of perfusion pressure and MBF, decreased by 20% (P < 0.001). In conclusion, the human coronary circulation is pressure distensible. MCE allows for the quantification of CR and MBV in humans.
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Thomas Pilgrim, Peter Wenaweser, Fabienne Meuli, Christoph Huber, Stefan Stortecky, Christian Seiler, Stephan Zbinden, Bernhard Meier, Thierry Carrel, Stephan Windecker (2011)  Clinical outcome of high-risk patients with severe aortic stenosis and reduced left ventricular ejection fraction undergoing medical treatment or TAVI.   PLoS One 6: 11. 11  
Abstract: Reduced left ventricular function in patients with severe symptomatic valvular aortic stenosis is associated with impaired clinical outcome in patients undergoing surgical aortic valve replacement (SAVR). Transcatheter Aortic Valve Implantation (TAVI) has been shown non-inferior to SAVR in high-risk patients with respect to mortality and may result in faster left ventricular recovery.
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Niklas Millauer, Peter Jueni, Alexandra Hofmann, Simon Wandel, Anupham Bhambhani, Michael Billinger, Niklaus Urwyler, Peter Wenaweser, Gerrit Hellige, Lorenz Raeber, Stephane Cook, Rolf Vogel, Mario Togni, Christian Seiler, Bernhard Meier, Stephan Windecker (2011)  Sirolimus Versus Paclitaxel Coronary Stents in Clinical Practice   CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS 77: 1. 5-12 JAN 1  
Abstract: Objectives: We aimed at comparing the long term clinical outcome of SES and PES in routine clinical practice. Background: Although sirolimus-eluting stents (SES) more effectively reduce neointimal hyperplasia than paclitaxel-eluting stents (PES), uncertainty prevails whether this difference translates into differences in clinical outcomes outside randomized controlled trials with selected patient populations and protocol-mandated angiographic follow-up. Methods: Nine hundred and four consecutive patients who underwent implantation of a drug-eluting stent between May 2004 and February 2005: 467 patients with 646 lesions received SES, 437 patients with 600 lesions received PES. Clinical follow-up was obtained at 2 years without intervening routine angiographic follow-up. The primary endpoint was a composite of death, myocardial infarction (MI), or target vessel revascularization (TVR). Results: At 2 years, the primary endpoint was less frequent with SES (12.9%) than PES (17.6%, HR = 0.70, 95% CI 0.50-0.98, P = 0.04). The difference in favor of SES was largely driven by a lower rate of target lesion revascularisation (TLR; 4.1% vs. 6.9%, P = 0.05), whereas rates of death (6.4% vs. 7.6%, P = 0.49), MI (1.9% vs. 3.2%, P = 0.21), or definite stent thrombosis (0.6% vs. 1.4%, P = 0.27) were similar for both stent types. The benefit regarding reduced rates of TLR was significant in nondiabetic (3.6% vs. 7.1%, P = 0.04) but not in diabetic patients (5.6% vs. 6.1%, P = 0.80). Conclusions: SES more effectively reduced the need for repeat revascularization procedures than PES when used in routine clinical practice. The beneficial effect is maintained up to 2 years and may be less pronounced in diabetic patients. (C) 2010 Wiley-Liss, Inc.
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2010
Pascal Meier, Steffen Gloekler, Stefano F de Marchi, Rainer Zbinden, Etienne Delacrétaz, Christian Seiler (2010)  An indicator of sudden cardiac death during brief coronary occlusion: electrocardiogram QT time and the role of collaterals.   Eur Heart J 31: 10. 1197-1204 May  
Abstract: The coronary collateral circulation has a beneficial role regarding all-cause and cardiac mortality. Hitherto, the underlying mechanism has not been clarified. The aim of this prospective study was to assess the effect of the coronary collateral circulation on electrocardiogram (ECG) QTc time change during short-term myocardial ischaemia.
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Rolf Vogel, Tobias Traupe, Valérie Stolt Steiger, Christian Seiler (2010)  Physical coronary arteriogenesis: a human "model" of collateral growth promotion.   Trends Cardiovasc Med 20: 4. 129-133 May  
Abstract: In patients with coronary artery disease, the size of myocardial infarction mainly determines the subsequent clinical outcome. Accordingly, it is the primary strategy to decrease cardiovascular mortality by minimizing infarct size. Promotion of collateral artery growth (arteriogenesis) is an appealing option of reducing infarct size. It has been demonstrated in experimental models that tangential fluid shear stress is the major trigger of arterial remodeling and, thus, of collateral growth. Lower-leg, high-pressure external counterpulsation triggered to occur during diastole induces a flow velocity signal and thus tangential endothelial shear stress in addition to the flow signal caused by cardiac stroke volume. We here present two cases of cardiac transplant recipients as human "models" of physical coronary arteriogenesis, providing an example of progressing and regressing clinical arteriogenesis, and review available evidence from clinical studies on other feasible forms of physical arteriogenesis.
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Mario Togni, Steffen Gloekler, Pascal Meier, Stefano F de Marchi, Tobias Rutz, Hélène Steck, Tobias Traupe, Christian Seiler (2010)  Instantaneous coronary collateral function during supine bicycle exercise.   Eur Heart J 31: 17. 2148-2155 Sep  
Abstract: The instantaneous response of the collateral circulation to isometric physical exercise in patients with non-occlusive coronary artery disease (CAD) is not known.
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Pascal Meier, Christian Seiler (2010)  Sudden Cardiac Arrest during Acute Coronary Occlusion - Who Is at Risk?   CARDIOLOGY 117: 2. 124-127  
Abstract: Many people with acute myocardial infarction die from sudden cardiac arrest before reaching the hospital. The current clinical understanding of the mechanisms and risk factors surrounding sudden cardiac death is limited. However, 2 factors related to sudden death, namely the occluded coronary vessel (right coronary, left circumflex, or left anterior descending artery) and the extent of collateral circulation, are of potential relevance. Recent data suggest that the risk differs between the different coronary arteries and that coronary collateral circulation seems to have an important protective ‘antiarrhythmic’ effect. This editorial will address possible mechanisms and potential implications in clinical practice. Copyright (C) 2010 S. Karger AG, Basel
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Tobias Rutz, Stefano F de Marchi, Markus Schwerzmann, Rolf Vogel, Christian Seiler (2010)  Right ventricular absolute myocardial blood flow in complex congenital heart disease   HEART 96: 13. 1056-1062 JUL  
Abstract: Objective A consequence in patients with d-transposition of the great arteries (d-TGA) and tetralogy of Fallot (TOF) is right ventricular hypertrophy (RVH) and right ventricular failure. Myocardial contrast echocardiography (MCE) permits the determination of the myocardial microvascular density reflected by the relative myocardial blood volume (rBV; ml/ml). This study was conducted to elucidate the relationship between RVH and myocardial microvascular changes by quantitative MCE in patients with d-TGA and TOF. Methods Three groups of individuals were included in the study: 22 patients with d-TGA, 18 patients with TOF and 22 healthy individuals (controls). MCE was performed at rest and during adenosine-induced hyperaemia. rBV and myocardial blood flow (MBF; ml/min per gram) were derived from steady state and refill sequences of ultrasound contrast agent. Results Hyperaemic septal rBV differed significantly between the groups and was highest in controls: d-TGA 0.141+/-0.060 ml/ml, TOF 0.134+/-0.080 ml/ml, controls 0.189+0.074 ml/ml, p=0.005. Myocardial blood flow reserve (MBFR), that is the ratio of hyperaemic to baseline MBF, differed significantly between the groups and was lowest in d-TGA (2.68+/-1.13) versus TOF (3.37+/-1.57) and controls (4.22+/-1.17, p=0.001). Hyperaemic septal rBV, MBF and MBFR showed a significant correlation with right ventricular systolic function as determined by tricuspid annular plane systolic excursion. Conclusions Right ventricular myocardial microvascular density of the septal wall in d-TGA and TOF patients with RVH due to pressure and/or volume overload is reduced. This appears to be related to a reduced myocardial perfusion reserve and impaired right ventricular systolic function.
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Steffen Gloekler, Tobias Traupe, Pascal Meier, Helene Steck, Stefano F de Marchi, Christian Seiler (2010)  Safety of Diagnostic Balloon Occlusion in Normal Coronary Arteries   AMERICAN JOURNAL OF CARDIOLOGY 105: 12. 1716-1722 JUN 15  
Abstract: Diagnostic coronary balloon occlusion (CBO) is mandatory for collateral function assessment, during angioscopy and optical coherence imaging, and when using certain coronary protection devices against emboli. Thus far, the safety of diagnostic CBO regarding procedural and long-term complications in normal coronary arteries has not been studied. In 316 patients, diagnostic CBO was performed for collateral function measurement in 426 angiographically normal vessels. The angioplasty balloon was inflated for 60 to 120 seconds using inflation pressures of 1 to 3 atm, followed by control angiography during and after CBO. Patients were divided into groups with entirely normal (n = 133) and partially normal (n = 183) vessels. Primary end points were procedural and long-term complications. De novo stenosis development was assessed by quantitative coronary angiography in 35% of the patients. Secondary end points were cardiac events at 5 years of follow-up. Procedural complications occurred in 1 patient (0.2%). in 150 repeat angiographic procedures in 92 patients (follow-up duration 10 +/- 15 months), quantitative coronary angiography revealed no difference in percentage diameter narrowing between baseline and follow-up (4.1% vs 3.9%, p = 0.69). During follow-up periods of 14 and 72 months, respectively, a new stenotic lesion was detected in 1 patient in each group (1.3%). Major cardiac events and percutaneous coronary intervention for stable angina were less frequent in the group with entirely normal than with partially normal vessels (0.8% vs 5.5%, p = 0.02, and 0.8% vs 18%, p<0.0001). In conclusion, low inflation pressure diagnostic CB in angiographically normal coronary arteries bears a minimal risk for procedural and long-term complications and can therefore be regarded as a safe procedure. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:1716-1722)
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Parham Eshtehardi, Patrick Adorjan, Mario Togni, Hendrick Tevaearai, Rolf Vogel, Christian Seiler, Bernhard Meier, Stephan Windecker, Thierry Carrel, Peter Wenaweser, Stephane Cook (2010)  Iatrogenic left main coronary artery dissection : Incidence, classification, management, and long-term follow-up   AMERICAN HEART JOURNAL 159: 6. 1147-1153 JUN  
Abstract: Background Although rare, iatrogenic left main coronary artery (LM) dissection is a feared complication of coronary catheterization. Its incidence, optimal therapeutic management, and prognosis remain largely unknown. The aim of the present study was to estimate the incidence, characterize the population at risk, depict the initial management, and evaluate the long-term prognosis of iatrogenic LM dissection. Methods Thirty-eight patients who fulfilled the National Heart, Lung, and Blood Institute diagnostic criteria for iatrogenic LM dissection were retrieved from our database and followed up by telephone or physician visit. The primary end point was freedom from major adverse cardiac events (MACE) at 5 years. Results The overall incidence of iatrogenic LM dissection during the study period was 0.07% (38/51,452 patients) and almost twice as common with percutaneous coronary intervention than coronary angiography. From 38 patients, 1 (3%) patient died before any therapeutic attempt was performed, 6 (16%) patients were treated conservatively, and 31 (82%) patients underwent stent implantation and/or coronary artery bypass grafting (CABG). In-hospital outcome was favorable irrespective of the therapeutic strategy. During the 5-year follow-up, among 31 patients who underwent revascularization treatment by stenting or CABG, one patient died in each group from a cardiac cause, and MACE were observed in 12 patients (39%). Kaplan-Meier cumulative survival estimates showed no significant difference between different revascularization treatment strategies. Conclusions Iatrogenic LM dissection is a rare complication of cardiac catheterization procedures with favorable early and long-term outcome when recognized timely and managed properly. (Am Heart J 2010;159:1147-53.)
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Mario Togni, Steffen Gloekler, Pascal Meier, Stefano F de Marchi, Tobias Rutz, Helene Steck, Tobias Traupe, Christian Seiler (2010)  Instantaneous coronary collateral function during supine bicycle exercise   EUROPEAN HEART JOURNAL 31: 17. 2148-2155 SEP  
Abstract: The instantaneous response of the collateral circulation to isometric physical exercise in patients with non-occlusive coronary artery disease (CAD) is not known. Thirty patients (age 59 +/- 9 years) undergoing percutaneous coronary intervention because of stable CAD were included in the study. Collateral function was determined before and during the last minute of a 6 min protocol of supine bicycle exercise during radial artery access coronary angiography. Collateral flow index (CFI, no unit) was determined as the ratio of mean distal coronary occlusive to mean aortic pressure both subtracted by central venous pressure. To avoid confounding due to recruitment of coronary collaterals by repetitive balloon occlusions, patients were randomly assigned to a group ‘rest first’ with CFI measurement during rest followed by CFI during exercise, and to a group ‘exercise first’ with antecedent CFI measurement during exercise before CFI at rest. Simultaneously, coronary collateral conductance (occlusive myocardial blood flow per aorto-coronary pressure drop) was determined by myocardial contrast echocardiography in the last 10 consecutive patients. Overall, CFI increased from 0.168 +/- 0.118 at rest to 0.262 +/- 0.166 during exercise (P = 0.0002). The exercise-induced change in CFI did not differ statistically in the two study groups. Exercise-induced CFI reserve (CFI during exercise divided by CFI at rest) was 2.2 +/- 1.8. Overall, rest to peak bicycle exercise change of coronary collateral conductance was from 0.010 +/- 0.010 to 1.109 +/- 0.139 mL/min/100 mmHg (P < 0.0001); the respective change was similar in both groups. In patients with non-occlusive CAD, collateral flow instantaneously doubles during supine bicycle exercise as compared with the resting state. ClinicalTrials.gov Identifier: NCT00947050.
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Pascal Meier, Steffen Gloekler, Stefano F de Marchi, Rainer Zbinden, Etienne Delacretaz, Christian Seiler (2010)  An indicator of sudden cardiac death during brief coronary occlusion : electrocardiogram QT time and the role of collaterals   EUROPEAN HEART JOURNAL 31: 10. 1197-1204 MAY  
Abstract: The coronary collateral circulation has a beneficial role regarding all-cause and cardiac mortality. Hitherto, the underlying mechanism has not been clarified. The aim of this prospective study was to assess the effect of the coronary collateral circulation on electrocardiogram (ECG) QTc time change during short-term myocardial ischaemia. A total of 150 patients (mean age 63 +/- 11 years, 38 women) were prospectively included in this study. An ECG was recorded at baseline and during a standardized 1 min coronary balloon occlusion. QT interval was measured before, during, and after balloon occlusion and was corrected for heart rate (QTc). Simultaneously obtained collateral flow index (CFI), expressing collateral flow relative to normal anterograde flow, was determined based on intracoronary pressure measurements. During occlusion of the left anterior descending coronary artery mean QTc interval increased from 422 +/- 33 to 439 +/- 36 ms (P < 0.001), left circumflex occlusion led to an increase from 414 +/- 32 to 427 +/- 27 ms (P < 0.001). QTc was not influenced by occlusion of the right coronary artery (RCA) (417 +/- 35 and 415 +/- 34 ms, respectively; P = 0.863). QTc change during occlusion of the left coronary artery was inversely correlated with CFI (R(2) = 0.122, P = 0.0002). Myocardial ischaemia leads to QT prolongation during a controlled 1 min occlusion of the left, but not the RCA. QT prolongation is inversely related to collateral function indicating a protective mechanism of human coronary collaterals against cardiac death.
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Christian Seiler (2010)  The human coronary collateral circulation   EUROPEAN JOURNAL OF CLINICAL INVESTIGATION 40: 5. 465-476 MAY  
Abstract: P>Background Coronary collaterals are an alternative source of blood supply to myocardium jeopardized by ischaemia. Well-developed coronary collateral arteries in patients with coronary artery disease (CAD) mitigate myocardial infarcts and improve survival. Methods and results Collateral arteries preventing myocardial ischaemia during brief vascular occlusion are present in 1/3 of patients with CAD. Among individuals without relevant coronary stenoses, there are preformed collateral arteries preventing myocardial ischaemia in 20-25%. Collateral flow sufficient to prevent myocardial ischaemia during coronary occlusion amounts to double dagger 25% of the normal flow through the open vessel. Myocardial infarct size, the most important prognostic determinant after such an event, is the product of coronary artery occlusion time, area at risk for infarction and the inverse of collateral supply. Coronary collateral flow can be assessed only during vascular occlusion of the collateral-receiving artery. The gold standard for coronary collateral assessment is the measurement of intracoronary occlusive pressure- or velocity-derived collateral flow index expressing collateral as a fraction of flow during vessel patency. Approximately one of five patients with CAD cannot be revascularized by percutaneous coronary intervention or coronary artery bypass grafting. Therapeutic promotion of collateral growth is a valuable treatment strategy in those patients. Conclusions Promotion of collateral growth should aim at inducing the development of large conductive collateral arteries (i.e. arteriogenesis) and not so much the sprouting of capillary like vessels (i.e. angiogenesis). Large conductive collateral arteries appear to be effectively promoted via the activation of monocytes/macrophages by means of granulocyte-colony stimulating factor or of augmenting coronary flow velocity.
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Lorenz Raeber, Peter Jueni, Lukas Loeffel, Simon Wandel, Stephane Cook, Peter Wenaweser, Mario Togni, Rolf Vogel, Christian Seiler, Franz Eberli, Thomas Luescher, Bernhard Meier, Stephan Windecker (2010)  Impact of Stent Overlap on Angiographic and Long-Term Clinical Outcome in Patients Undergoing Drug-Eluting Stent Implantation   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 55: 12. 1178-1188 MAR 23  
Abstract: Objectives We compared the angiographic and long-term clinical outcomes of patients with and without overlap of drug-eluting stents (DES). Background DES overlap has been associated with delayed healing and increased inflammation in experimental studies, but its impact on clinical outcome is not well established. Methods We analyzed the angiographic and clinical outcomes of 1,012 patients treated with DES in the SIRTAX (Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization) trial according to the presence or absence of stent overlap and the number of stents per vessel: 134 (13.2%) patients with multiple DES in a vessel with overlap, 199 (19.7%) patients with multiple DES in a vessel without overlap, and 679 (67.1%) patients with 1 DES per vessel. Results Angiographic follow-up at 8 months showed an increased late loss in DES overlap patients (0.33 +/- 0.61 mm) compared with the other groups (0.18 +/- 0.43 mm and 0.15 +/- 0.38 mm, p < 0.01). The smallest minimal lumen diameter was located at the zone of stent overlap in 17 (68%) of 25 patients with stent overlap who underwent target lesion revascularization. Major adverse cardiac events were more common in patients with DES overlap (34 events, 25.4%) than in the other groups (42 events, 21.1% and 95 events, 14.0%) at 3 years (p < 0.01). Both the risk of target lesion revascularization (20.2% vs. 16.1% vs. 9.7%, p < 0.01) and the composite of death or myocardial infarction (17.2% vs. 14.1% vs. 9.1%, p = 0.01) were increased in patients with DES overlap compared with the other groups. Conclusions DES overlap occurs in > 10% of patients undergoing percutaneous coronary intervention in routine clinical practice and is associated with impaired angiographic and long-term clinical outcome, including death or myocardial infarction. (Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization; NCT00297661). (J Am Coll Cardiol 2010; 55: 1178-88) (C) 2010 by the American College of Cardiology Foundation
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Steffen Gloekler, Pascal Meier, Stefano F de Marchi, Tobias Rutz, Tobias Traupe, Stefano F Rimoldi, Kerstin Wustmann, Helene Steck, Stephane Cook, Rolf Vogel, Mario Togni, Christian Seiler (2010)  Coronary collateral growth by external counterpulsation : a randomised controlled trial   HEART 96: 3. 202-207 FEB  
Abstract: Background The efficacy of external counterpulsation (ECP) on coronary collateral growth has not been investigated in a randomised controlled study. Objective To test the hypothesis that ECP augments collateral function during a 1 min coronary balloon occlusion. Patients and methods Twenty patients with chronic stable coronary artery disease were studied. Before and after 30 h of randomly allocated ECP (20 90 min sessions over 4 weeks at 300 mm Hg inflation pressure) or sham ECP (same setting at 80 mm Hg inflation pressure), the invasive collateral flow index (CFI, no unit) was obtained in 34 vessels without coronary intervention. CFI was determined by the ratio of mean distal coronary occlusive pressure to mean aortic pressure with central venous pressure subtracted from both. Additionally, coronary collateral conductance (occlusive myocardial blood flow per aorto-coronary pressure drop) was determined by myocardial contrast echocardiography, and brachial artery flow-mediated dilatation was obtained. Results CFI changed from 0.125 (0.073; interquartile range) at baseline to 0.174 (0.104) at follow-up in the ECP group (p=0.006), and from 0.129 (0.122) to 0.111 ( 0.125) in the sham ECP group (p=0.14). Baseline to follow-up change of coronary collateral conductance was from 0.365 (0.268) to 0.568 (0.585) ml/min/ 100 mm Hg in the ECP group (p=0.072), and from 0.229 (0.212) to 0.305 (0.422) ml/min/100 mm Hg in the sham ECP group (p=0.45). There was a correlation between the flow-mediated dilatation change from baseline to follow-up and the corresponding CFI change (r=0.584, p=0.027). Conclusions ECP appears to be effective in promoting coronary collateral growth. The extent of collateral function improvement is related to the amount of improvement in the systemic endothelial function.
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Rolf Vogel, Tobias Traupe, Valerie Stolt Steiger, Christian Seiler (2010)  Physical Coronary Arteriogenesis : A Human “Model†of Collateral Growth Promotion   TRENDS IN CARDIOVASCULAR MEDICINE 20: 4. 129-133 MAY  
Abstract: In patients with coronary artery disease, the size of myocardial infarction mainly determines the subsequent clinical outcome. Accordingly, it is the primary strategy to decrease cardiovascular mortality by minimizing infarct size. Promotion of collateral artery growth (arteriogenesis) is an appealing option of reducing infarct size. It has been demonstrated in experimental models that tangential fluid shear stress is the major trigger of arterial remodeling and, thus, of collateral growth. Lower-leg, high-pressure external counterpulsation triggered to occur during diastole induces a flow velocity signal and thus tangential endothelial shear stress in addition to the flow signal caused by cardiac stroke volume. We here present two cases of cardiac transplant recipients as human “models†of physical coronary arteriogenesis, providing an example of progressing and regressing clinical arteriogenesis, and review available evidence from clinical studies on other feasible forms of physical arteriogenesis. (Trends Cardiovasc Med 2010;20:129-133) (C) 2010 Published by Elsevier Inc.
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Pascal Meier, Christian Seiler (2010)  Sudden cardiac arrest during acute coronary occlusion - who is at risk?   Cardiology 117: 2. 124-127 10  
Abstract: Many people with acute myocardial infarction die from sudden cardiac arrest before reaching the hospital. The current clinical understanding of the mechanisms and risk factors surrounding sudden cardiac death is limited. However, 2 factors related to sudden death, namely the occluded coronary vessel (right coronary, left circumflex, or left anterior descending artery) and the extent of collateral circulation, are of potential relevance. Recent data suggest that the risk differs between the different coronary arteries and that coronary collateral circulation seems to have an important protective 'antiarrhythmic' effect. This editorial will address possible mechanisms and potential implications in clinical practice.
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2009
R Vogel, A Indermuehle, P Meier, C Seiler (2009)  Quantitative stress echocardiography in coronary artery disease using contrast-based myocardial blood flow measurements : prospective comparison with coronary angiography   HEART 95: 5. 377-124 MAR  
Abstract: Aim: To test whether quantitative stress echocardiography using contrast-based myocardial blood flow (MBF, ml.min(-1).g(-1)) measurements can detect coronary artery disease in humans. Methods: 48 patients eligible for pharmacological stress testing by myocardial contrast echocardiography (MCE) and willing to undergo subsequent coronary angiography were prospectively enrolled in the study. Baseline and adenosine-induced (140 mu g.kg(-1).min(-1)) hyperaemic MBF was analysed according to a three-coronary-artery-territory model. Vascular territories were categorised into three groups with increasing stenosis severity defined as percentage diameter reduction by quantitative coronary angiography. Results: Myocardial blood flow reserve (MBFR)-that is, the ratio of hyperaemic to baseline MBF, was obtained in 128 (89%) territories. Mean (SD) baseline MBF was 1.073 (0.395) ml.min(-1).g(-1) and did not differ between territories supplied by coronary arteries with mild (<50% stenosis), moderate (50%-74% stenosis) or severe (>= 75% stenosis) disease. Mean (SD) hyperaemic MBF and MBFR were 2.509 (1.078) ml.min(-1).g(-1) and 2.54 (1.03), respectively, and decreased linearly (r(2) = 0.21 and r(2) = 0.39) with stenosis severity. ROC analysis revealed that a territorial MBFR <1.94 detected >= 50% stenosis with 89% sensitivity and 92% specificity. Conclusion: Quantitative stress testing based on MBF measurements derived from contrast echocardiography is a new method for the non-invasive and reliable assessment of coronary artery disease in humans.
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P Meier, J Antonov, R Zbinden, A Kuhn, S Zbinden, S Gloekler, M Delorenzi, R Jaggi, C Seiler (2009)  Non-invasive gene-expression-based detection of well-developed collateral function in individuals with and without coronary artery disease   HEART 95: 11. 900-908 JUN  
Abstract: Background: In patients with coronary artery disease (CAD), a well grown collateral circulation has been shown to be important. The aim of this prospective study using peripheral blood monocytes was to identify marker genes for an extensively grown coronary collateral circulation. Methods: Collateral flow index (CFI) was obtained invasively by angioplasty pressure sensor guidewire in 160 individuals (110 patients with CAD, and 50 individuals without CAD). RNA was extracted from monocytes followed by microarray-based gene-expression analysis. 76 selected genes were analysed by real-time polymerase chain reaction (PCR). A receiver operating characteristics analysis based on differential gene expression was then performed to separate individuals with poor (CFI < 0.21) and well-developed collaterals (CFI >= 0.21) Thereafter, the influence of the chemokine MCP-1 on the expression of six selected genes was tested by PCR. Results: The expression of 203 genes significantly correlated with CFI (p = 0.000002-0.00267) in patients with CAD and 56 genes in individuals without CAD (p= 00079-0.0430). Biological pathway analysis revealed 76 of those genes belonging to four different pathways: angiogenesis, integrin-, platelet-derived growth factor-, and transforming growth factor beta-signalling. Three genes in each subgroup differentiated with high specificity among individuals with low and high CFI (>= 0.21). Two out of these genes showed pronounced differential expression between the two groups after cell stimulation with MCP-1. Conclusions: Genetic factors play a role in the formation and the preformation of the coronary collateral circulation. Gene expression analysis in peripheral blood monocytes can be used for non-invasive differentiation between individuals with poorly and with well grown collaterals. MCP-1 can influence the arteriogenic potential of monocytes.
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Stephane Cook, Elena Ladich, Gaku Nakazawa, Parham Eshtehardi, Michel Neidhart, Rolf Vogel, Mario Togni, Peter Wenaweser, Michael Billinger, Christian Seiler, Steffen Gay, Bernhard Meier, Werner J Pichler, Peter Jueni, Renu Virmani, Stephan Windecker (2009)  Correlation of Intravascular Ultrasound Findings With Histopathological Analysis of Thrombus Aspirates in Patients With Very Late Drug-Eluting Stent Thrombosis   CIRCULATION 120: 5. 391-399 AUG 4  
Abstract: Background-Intravascular ultrasound of drug-eluting stent ( DES) thrombosis (ST) reveals a high incidence of incomplete stent apposition (ISA) and vessel remodeling. Autopsy specimens of DES ST show delayed healing and hypersensitivity reactions. The present study sought to correlate histopathology of thrombus aspirates with intravascular ultrasound findings in patients with very late DES ST. Methods and Results-The study population consisted of 54 patients (28 patients with very late DES ST and 26 controls). Of 28 patients with very late DES ST, 10 patients (1020 +/- 283 days after implantation) with 11 ST segments (5 sirolimus-eluting stents, 5 paclitaxel-eluting stents, 1 zotarolimus-eluting stent) underwent both thrombus aspiration and intravascular ultrasound investigation. ISA was present in 73% of cases with an ISA cross-sectional area of 6.2 +/- 2.4 mm(2) and evidence of vessel remodeling (index, 1.6 +/- 0.3). Histopathological analysis showed pieces of fresh thrombus with inflammatory cell infiltrates (DES, 263 +/- 149 white blood cells per high-power field) and eosinophils (DES, 20 +/- 24 eosinophils per high-power field; sirolimus-eluting stents, 34 +/- 28; paclitaxel-eluting stents, 6 +/- 6; P for sirolimus-eluting stents versus paclitaxel-eluting stents=0.09). The mean number of eosinophils per high-power field was higher in specimens from very late DES ST (20 +/- 24) than in those from spontaneous acute myocardial infarction (7 +/- 10), early bare-metal stent ST (1 +/- 1), early DES ST (1 +/- 2), and late bare-metal stent ST (2 +/- 3; P from ANOVA=0.038). Eosinophil count correlated with ISA cross-sectional area, with an average increase of 5.4 eosinophils per high-power field per 1-mm(2) increase in ISA cross-sectional area. Conclusions-Very late DES thrombosis is associated with histopathological signs of inflammation and intravascular ultrasound evidence of vessel remodeling. Compared with other causes of myocardial infarction, eosinophilic infiltrates are more common in thrombi harvested from very late DES thrombosis, particularly in sirolimus-eluting stents, and correlate with the extent of stent malapposition. (Circulation. 2009;120:391-399.)
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Andreas Indermuehle, Rolf Vogel, Tobias Rutz, Pascal Meier, Christian Seiler (2009)  Myocardial contrast echocardiography for the distinction of hypertrophic cardiomyopathy from athlete’s heart and hypertensive heart disease   SWISS MEDICAL WEEKLY 139: 47-48. 691-698 NOV 28  
Abstract: Background: Myocardial contrast echocardiography (MCE) is able to measure in vivo relative blood volume (rBV, i.e., capillary density), and its exchange frequency P, the constituents of myocardial blood flow (MBF, ml min(-1) g(-1)). This study aimed to assess, by, MCE, whether left ventricular hypertrophy (LVH) in hypertrophic cardiomyopathy (HCM) can be differentiated from LVH in triathletes (athlete’s heart, AH) or from hypertensive heart disease patients (HHD). Methods: Sixty individuals, matched for age (33 +/- 10 years) and gender, and subdivided into four groups (n = 15) were examined: HCM, AH, HHD and a group of sedentary individuals without LVH (S). rBV (ml ml(-1)), beta (min(-1)) and MBF, at rest and during adenosine-induced hyperaemia, were derived by MCE in mid septal, lateral and inferior regions. The ratio of MBF during hyperaemia and MBF at rest yielded myocardial blood flow reserve (MBFR). Results: Septal wall rBV at rest was lower in HCM (0.084 +/- 0.02 3 ml ml(-1)) than in AH (0.151 +/- 0.024 ml ml(-1), p < 0.01) and in S (0.129 +/- 0.026 ml ml(-1), p < 0.01), but was similar to HHD (0.097 +/- 0.016 ml ml(-1)). Conversely, MBFR was lowest in HCM (1.67 +/- 0.93), followed by HHD (2.8 +/- 0.93, p < 0.01), by S (3.36 +/- 1.03, p < 0.001) and by AH (4.74 +/- 1.46, p < 0.0001). At rest, rBV < 0.11 ml ml(-1) accurately distinguished between HCM and AH (sensitivity 99%, specificity 99%), similarly MBFR <= 1.8 helped to distinguish between HCM and HHD (sensitivity 100%, specificity 77%). Conclusions: rBV at rest, most accurately distinguishes between pathological LVH due to HCM and. physiological, endurance-exercise induced LVH.
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Pascal Meier, Steffen Gloekler, Stefano F de Marchi, Andreas Indermuehle, Tobias Rutz, Tobias Traupe, Helene Steck, Rolf Vogel, Christian Seiler (2009)  Myocardial Salvage Through Coronary Collateral Growth by Granulocyte Colony-Stimulating Factor in Chronic Coronary Artery Disease A Controlled Randomized Trial   CIRCULATION 120: 14. 1355-1363 OCT 6  
Abstract: Background-The efficacy of granulocyte colony-stimulating factor (G-CSF) for coronary collateral growth promotion and thus impending myocardial salvage has not been studied so far, to our best knowledge. Methods and Results-In 52 patients with chronic stable coronary artery disease, age 62+/-11 years, the effect on a marker of myocardial infarct size (ECG ST segment elevation) and on quantitative collateral function during a 1-minute coronary balloon occlusion was tested in a randomized, placebo-controlled, double-blind fashion. The study protocol before coronary intervention consisted of occlusive surface and intracoronary lead ECG recording as well as collateral flow index (CFI, no unit) measurement in a stenotic and a >= 1 normal coronary artery before and after a 2-week period with subcutaneous G-CSF (10 mu g/kg; n=26) or placebo (n=26). The CFI was determined by simultaneous measurement of mean aortic, distal coronary occlusive, and central venous pressure. The ECG ST segment elevation >0.1 mV disappeared significantly more often in response to G-CSF (11/53 vessels; 21%) than to placebo (0/55 vessels; P=0.0005), and simultaneously, CFI changed from 0.121+/-0.087 at baseline to 0.166+/-0.086 at follow-up in the G-CSF group, and from 0.152+/-0.082 to 0.131+/-0.071 in the placebo group (P<0.0001 for interaction of treatment and time). The absolute change in CFI from baseline to follow-up amounted to +0.049+/-0.062 in the G-CSF group and to -0.010+/-0.060 in the placebo group (P<0.0001). Conclusions-Subcutaneous G-CSF is efficacious during a short-term protocol in improving signs of myocardial salvage by coronary collateral growth promotion. (Circulation. 2009;120:1355-1363.)
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Andreas Wahl, Tony Tai, Fabien Praz, Markus Schwerzmann, Christian Seiler, Krassen Nedeltchev, Stephan Windecker, Heinrich P Mattle, Bernhard Meier (2009)  Late Results After Percutaneous Closure of Patent Foramen Ovale for Secondary Prevention of Paradoxical Embolism Using the Amplatzer PFO Occluder Without Intraprocedural Echocardiography Effect of Device Size   JACC-CARDIOVASCULAR INTERVENTIONS 2: 2. 116-123 FEB  
Abstract: Objectives We sought to assess the safety and clinical efficacy of patent foramen ovale (PFO) closure under fluoroscopic guidance only, without intraprocedural echocardiography. Background Percutaneous PFO closure has been shown to be safe and feasible using several devices. It is generally performed using simultaneously fluoroscopic and transesophageal or intracardiac echocardiographic guidance. Transesophageal echocardiography requires sedation or general anesthesia and intubation to avoid aspiration. Intracardiac echocardiography is costly and has inherent risks. Both lengthen the procedure. The Amplatzer PFO Occluder (AGA Medical Corporation, Golden Valley, Minnesota) can be safely implanted without echocardiographic guidance. Methods A total of 620 patients (51 +/- 12 years; 66% male) underwent PFO closure using the Amplatzer PFO Occluder for secondary prevention of presumed paradoxical embolism. Based on size and mobility of the PFO and the interatrial septum, an 18-mm device was used in 50 patients, a 25-mm device in 492, and a 35-mm device in 78. Results All procedures were successful, with 5 procedural complications (0.8%): 4 arteriovenous fistulae requiring elective surgical correction, and 1 transient ischemic attack. Contrast transesophageal echocardiography at 6 months showed complete closure in 91% of patients, whereas a minimal, moderate, or large residual shunt persisted in 6%, 2%, and 1%, respectively. During a mean follow-up period of 3.0 +/- 1.9 years (median: 2.6 years; total patient-years: 1,871), 5 ischemic strokes, 8 transient ischemic attacks, and no peripheral emboli were reported. Freedom from recurrent ischemic stroke, transient ischemic attack, or peripheral embolism was 99% at 1 year, 99% at 2 years, and 97% at 5 years. Conclusions The Amplatzer PFO Occluder affords excellent safety and long-term clinical efficacy of percutaneous PFO closure without intraprocedural echocardiography. (J Am Coll Cardiol Intv 2009; 2:116-23) (C) 2009 by the American College of Cardiology Foundation
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2008
Michael Billinger, Jonas Beutler, Keywan R Taghetchian, Andrea Remondino, Peter Wenaweser, Stephane Cook, Mario Togni, Christian Seiler, Christoph Stettler, Franz R Eberli, Thomas F Luescher, Simon Wandel, Peter Jueni, Bernhard Meier, Stephan Windecker (2008)  Two-year clinical outcome after implantation of sirolimus-eluting and paclitaxel-eluting stents in diabetic patients   EUROPEAN HEART JOURNAL 29: 6. 718-725 MAR  
Abstract: Aims Percutaneous coronary intervention (PCI) in diabetic patients is associated with an increased risk of restenosis and major adverse cardiac events (MACE). We assessed the impact of diabetes on long-term outcome after PCI with sirolimus-eluting (SES) and paclitaxel-eluting (PES) stents. Methods and results In the SIRTAX trial, 1012 patients were randomized to treatment with SES (n = 503) or PES (n = 509). A stratified analysis of outcomes was performed according to the presence or absence of diabetes. Baseline characteristics were well balanced between SES and PES in patients with (N = 201) and without diabetes (N = 811). Clinical outcome was worse in diabetic compared with non-diabetic patients regarding death (9.0% vs. 4.1%, P = 0.004) and MACE ( defined as cardiac death, myocardial infarction, or TLR; 19.9% vs. 12.7%, P = 0.007) at 2 years. Among diabetic patients, SES reduced MACE by 47% ( 14.8% vs. 25.8%, HR = 0.52, P = 0.05) and TLR by 61% ( 7.4% vs. 17.2%, HR = 0.39, P = 0.03) compared with PES at 2 years. Conclusion Diabetic patients have worse prognosis than non-diabetic patients undergoing PCI with DES. Among the diabetic patient population of this trial, SES reduce repeat revascularization procedures and MACE more effectively than PES and to a similar degree as in non-diabetic patients.
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Andreas Wahl, Fabien Praz, Jessica Stirnimann, Stephan Windecker, Christian Seiler, Krassen Nedeltchev, Heinrich P Mattle, Bernhard Meier (2008)  Safety and feasibility of percutaneous closure of patent foramen ovale without intra-procedural echocardiography in 825 patients   SWISS MEDICAL WEEKLY 138: 39-40. 567-572 OCT 4  
Abstract: Background: Percutaneous closure of patent foramen ovale (PFO) is generally performed using infra-procedural guidance by transoesophageal (TEE) or intracardiac (ICE) echocardiography. While TEE requires sedation or general anaesthesia, ICE is costly and adds incremental risk, and both imaging modalities lengthen the procedure. Methods: A total of 825 consecutive patients (age 51 +/- 13 years; 58% male) underwent percutaneous PFO closure solely under fluoroscopic guidance, without infra-procedural echocardiography. The indications for PFO closure were presumed paradoxical embolism in 698 patients (95% cerebral, 5% other locations), an embolic event with concurrent aetiologies in 47, diving in 51, migraine headaches in 13, and other reasons in 16. An atrial septal aneurysm was associated with the PFO in 242 patients (29%). Results: Permanent device implantation failed in two patients (0.2%). There were 18 procedural complications (2.2%), including embolization of the device or parts of it in five patients with successful percutaneous removal in all cases, air embolism with transient symptoms in four patients, pericardial tamponade requiring pericardiocentesis in one patient, a transient ischaemic attack with visual symptoms in one patient, and vascular access site problems in seven patients. There were no long-term sequelae. Contrast TEE at six months showed complete abolition of right-to-left shunt via PFO in 88% of patients, whereas a minimal, moderate or large residual shunt persisted in 7%, 3 %, and 2 %, respectively. Conclusions: This study confirms the safety and feasibility of percutaneous PFO closure without intra-procedural echocardiographic guidance in a large cohort of consecutive patients.
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Peter Wenaweser, Jean-Franqois Surmely, Stephan Windecker, Marco Roffi, Mario Togni, Michael Billinger, Stephane Cook, Rolf Vogel, Christian Seiler, Otto M Hess, Bernhard Meier (2008)  Prognostic value of early exercise testing after coronary stent implantation   AMERICAN JOURNAL OF CARDIOLOGY 101: 6. 807-811 MAR 15  
Abstract: The clinical value of early exercise stress testing (EST) after coronary stenting to predict long-term clinical outcomes is unknown. Of 1,000 unselected patients who underwent coronary stenting, 446 random patients underwent early EST the day after intervention. Clinical long-term outcomes (41 +/- 20 months) were correlated with normal (n = 314 [70%]) or positive (n = 102 [23%]) EST results. Patients with inconclusive test results (n = 30 [7%]) were excluded from the analysis. Overall mortality was significantly higher in patients with positive EST results (9.3% vs 3.9%, p = 0.04). Major adverse cardiac events and cardiac mortality also tended to be higher in patients with positive stress test results (45.4% vs 35.4%, p = 0.08, and 4.1% vs 1.1%, p = 0.05, respectively). Patients with the combination of positive stress test results and incomplete revascularization appeared to be the group at highest risk for major adverse cardiac events (47.1% vs 33.3% for patients with normal stress test results and complete revascularization, p = NS). Negative stress test results reduced (odds ratio 0.329, 95% confidence interval 0.120 to 0.905, p = 0.031) and a lower ejection fraction increased (odds ratio 0.942, 95% confidence interval 0.897 to 0.989, p = 0.017) the risk for death. In conclusion, an. early stress test after coronary stenting provides important prognostic information. Positive stress test results, especially in combination with incomplete revascularization, are associated with higher mortality, a trend toward more repeat revascularization procedures, and higher risk for major adverse cardiac events. (C) 2008 Elsevier Inc. All rights reserved.
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A Wahl, M Kunz, A Moschovitis, T Nageh, M Schwerzmann, C Seiler, H P Mattle, S Windecker, B Meier (2008)  Long-term results after fluoroscopy-guided closure of patent foramen ovale for secondary prevention of paradoxical embolism   HEART 94: 3. 336-341 MAR  
Abstract: Objectives: To carry out long-term follow-up after percutaneous closure of patent foramen ovale (PFO) in patients with cryptogenic stroke. Design: Prospective cohort study. Setting: Single tertiary care centre. Participants: 525 consecutive patients (mean (SD) age 51 (12) years; 56% male). Interventions: Percutaneous PFO closure without intra-procedural echocardiography. Main outcome measures: Freedom from recurrent embolic events. Results: A mean (SD) of 1.7 (1.0) clinically apparent embolic events occurred for each patient, and 186 patients (35%) had >1 event. An atrial septal aneurysm was associated with the PFO in 161 patients (31%). All patients were followed up prospectively for up to 11 years. The implantation procedure failed in two patients (0.4%). There were 13 procedural complications (2.5%) without any long-term sequelae. Contrast transoesophageal echocardiography at 6 months showed complete closure in 86% of patients, and a minimal, moderate or large residual shunt in 9%, 3% and 2%, respectively. Patients with small occluders (, 30 mm; n = 429) had fewer residual shunts (small 11% vs large 27%; p<0.001). During a mean (SD) follow-up of 2.9 (2.2) years (median 2.3 years; total 1534 patient-years), six ischaemic strokes, nine transient ischaemic attacks (TIAs) and two peripheral emboli occurred. Freedom from recurrent stroke, TIA, or peripheral embolism was 98% at 1 year, 97% at 2 years and 96% at 5 and 10 years, respectively. A residual shunt (hazard ratio = 3.4; 95% CI 1.3 to 9.2) was a risk factor for recurrence. Conclusions: This study attests to the long-term safety and efficacy of percutaneous PFO closure guided by fluoroscopy only for secondary prevention of paradoxical embolism in a large cohort of consecutive patients.
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2007
Rainer Zbinden, Stephan Zbinden, Pascal Meier, Damian Hutter, Michael Billinger, Andreas Wahl, Jean-Paul Schmid, Stephan Winclecker, Bernhard Meier, Christian Seiler (2007)  Coronary collateral flow in response to endurance exercise training   EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION & REHABILITATION 14: 2. 250-257 APR  
Abstract: Background In humans, it is not known whether physical endurance exercise training promotes coronary collateral growth. The following hypotheses were tested: the expected collateral flow reduction after percutaneous coronary intervention of a stenotic lesion is prevented by endurance exercise training; collateral flow supplied to an angiographically normal coronary artery improves in response to exercise training; there is a direct relationship between the change of fitness after training and the coronary collateral flow change. Methods and results Forty patients (age 61 8 years) underwent a 3-month endurance exercise training program with baseline and follow-up assessments of coronary collateral flow. Patients were divided into an exercise training group n=24) and a sedentary group n=16) according to the fact whether they adhered or not to the prescribed exercise program, and whether or not they showed increased endurance (VO2max in ml/min per kg) and performance (W/kg) during follow-up versus baseline bicycle spiroergometry. Collateral flow index (no unit) was obtained using pressure sensor guidewires positioned in the coronary artery undergoing percutaneous coronary intervention and in a normal vessel. In the vessel initially undergoing percutaneous coronary intervention, there was an increase in collateral flow index among exercising but not sedentary patients from 0.155 +/- 0.081 to 0.204 +/- 0.056 (P= 0.03) and from 0.189 +/- 0.084 to 0.212 +/- 0.077 (NS), respectively. In the normal vessel, collateral flow index changes were from 0.176 +/- 0.075 to 0.227 +/- 0.070 in the exercise group (P=0.0002), and from 0.219 +/- 0.103 to 0.238 +/- 0.086 in the sedentary group (NS). A direct correlation existed between the change in collateral flow index from baseline to follow-up and the respective alteration of VO(2)max (P=0.007) and Waft (P=0.03). Conclusion A 3-month endurance exercise training program augments coronary collateral supply to normal vessels, and even to previously stenotic arteries having undergone percutaneous coronary intervention before initiating the program. There appears to be a dose-response relation between coronary collateral flow augmentation and exercise capacity gained.
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Pascal Meier, Rainer Zbinden, Mario Togni, Peter Wenaweser, Stephan Windecker, Bernhard Meier, Christian Seiler (2007)  Coronary collateral function long after drug-eluting stent implantation   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 49: 1. 15-20 JAN 2  
Abstract: Objectives This study was designed to compare coronary collateral function in patients after bare-metal stent (BMS) or drug-eluting stent (DES) implantation. Background Drug-eluting stents have an inhibitory effect on the production of cytokines, chemotactic proteins, and growth factors, and may therefore negatively affect coronary collateral growth. Methods A total of 120 patients with long-term stable coronary artery disease (CAD) after stent implantation were included. Both the BMS group and the DES group comprised 60 patients matched for in-stent stenosis severity of the vessel undergoing collateral flow index (CFI) measurement at follow-up and for the duration of follow-up. The primary end point of the investigation was invasively determined coronary collateral function 6 months after stent implantation. Collateral function was assessed by simultaneous aortic, coronary wedge, and central venous pressure measurements (yielding CFI) and by intracoronary electrocardiogram during balloon occlusion. Results There were no differences between the groups regarding age, gender, body mass index, frequency of cardiovascular risk factors, use of cardiovascular drugs, severity of CAD, or site of coronary artery stenoses. Despite equal in-stent stenosis severity (46 +/- 34% and 45 +/- 36%) and equal follow-up duration (6.2 +/- 10 months and 6.5 +/- 5.4 months), CFI was diminished in the DES versus BMS group (0.154 +/- 0.097 vs. 0.224 +/- 0.142; p = 0.0049), and the rate of collaterals insufficient to prevent ischemia during occlusion (intracoronary electrocardiographic ST-segment elevation >= 0.1 mV) was higher with 50 of 60 patients in the DES group and 33 of 60 patients in the BMS group (p = 0.001). Conclusions Collateral function long after coronary stenting is impaired with DES (sirolimus and paclitaxel) when compared with BMS. Considering the protective nature of collateral vessels, this could lead to more serious cardiac events in the presence of an abrupt coronary occlusion. (c) 2007 by the American College of Cardiology Foundation
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Stephane Cook, Peter Wenaweser, Mario Togni, Michael Billinger, Cyrill Morger, Christian Seiler, Rolf Vogel, Otto Hess, Bernhard Meier, Stephan Windecker (2007)  Incomplete stent apposition and very late stent thrombosis after drug-eluting stent implantation   CIRCULATION 115: 18. 2426-2434 MAY 8  
Abstract: Background - Stent thrombosis may occur late after drug-eluting stent (DES) implantation, and its cause remains unknown. The present study investigated differences of the stented segment between patients with and without very late stent thrombosis with the use of intravascular ultrasound. Methods and Results - Since January 2004, patients presenting with very late stent thrombosis (> 1 year) after DES implantation underwent intravascular ultrasound. Findings in patients with very late stent thrombosis were compared with intravascular ultrasound routinely obtained 8 months after DES implantation in 144 control patients, who did not experience stent thrombosis for >= 2 years. Very late stent thrombosis was encountered in 13 patients at a mean of 630 +/- 166 days after DES implantation. Compared with DES controls, patients with very late stent thrombosis had longer lesions (23.9 +/- 16.0 versus 13.3 +/- 7.9 mm; P < 0.001) and stents (34.6 +/- 22.4 versus 18.6 +/- 9.5 mm; P < 0.001), more stents per lesion (1.6 +/- 0.9 versus 1.1 +/- 0.4; P < 0.001), and stent overlap (39% versus 8%; P < 0.001). Vessel cross-sectional area was similar for the reference segment (cross-sectional area of the external elastic membrane: 18.9 +/- 6.9 versus 20.4 +/- 7.2 mm(2); P=0.46) but significantly larger for the in-stent segment (28.6 +/- 11.9 versus 20.1 +/- 6.7 mm(2); P=0.03) in very late stent thrombosis patients compared with DES controls. Incomplete stent apposition was more frequent (77% versus 12%; P < 0.001) and maximal incomplete stent apposition area was larger (8.3 +/- 7.5 versus 4.0 +/- 3.8 mm(2); P=0.03) in patients with very late stent thrombosis compared with controls. Conclusions - Incomplete stent apposition is highly prevalent in patients with very late stent thrombosis after DES implantation, suggesting a role in the pathogenesis of this adverse event.
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Andreas Wahl, Fabien Praz, Christian Seiler, Stephan Windecker, Bernhard Meier (2007)  Clinical relevance of coronary angiography at the time of percutaneous closure of a patent foramen ovale   CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS 70: 5. 641-645 NOV 1  
Abstract: Background: The value of incidental coronary angiography during percutaneous shunt closure to screen for asymptomatic coronary artery disease (CAD) is unknown. Methods: On the occasion of percutaneous closure of patent foramen ovale (PFO), incidental coronary angiography routinely offered to men >40 and women >50 years, or younger patients with particular risk patterns, was performed in 575 patients (64% men, mean age 55 +/- 10 years, mean 1.5 +/- 1.1 cardiovascular risk factors) without overt history, signs, or symptoms of CAD. Results: CAD was found in 164 patients (29%); 53 (9%) had >= 50% diameter stenoses. Thirty patients (5%) had one-vessel, 13 (2%) two-vessel, and 10 (2%) three-vessel disease. Patients with CAD (n = 164) were older (60 9 vs. 53 10 years; P < 0.0001), more frequently male (76% vs. 59%; P = 0.0002), and had a higher body mass index (26.5 +/- 4.0 vs. 25.4 +/- 4.6; P = 0.006) and more cardiovascular risk factors (2.0 +/- 1.1 vs. 1.2 +/- 1.0; P < 0.0001). There were six procedural complications (1%). Two were unequivocally related to coronary angiography: one minor stroke (diplopia), and one iatrogenic dissection of the right coronary ostium requiring stenting. Furthermore, four arteriovenous fistulae at the puncture site requiring elective surgical closure were possibly related to coronary angiography. Forty-five patients (8% of total) underwent percutaneous (n = 43) or surgical (n = 2) revascularization. Conclusions: In selected asymptomatic patients referred for percutaneous PFO closure, incidental coronary angiography discloses a rather high prevalence of clinically unsuspected CAD. These findings are relevant not only for timely revascularization but also for maintenance of long-term antiplatelet therapy beyond the few months recommended after PFO closure. 2) 2007 Wiley-Liss, Inc.
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Peter Wenaweser, Marianne Ramser, Stephan Windecker, Indira Luetolf, Bernhard Meier, Christian Seiler, Franz R Eberli, Otto M Hess (2007)  Outcome of elderly patients undergoing primary percutaneous coronary intervention for acute ST-elevation myocardial infarction   CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS 70: 4. 485-490 OCT 1  
Abstract: Aim: To investigate the outcome of primary percutaneous coronary interventions (PCI) in elderly patients ( >= 75 years) with ST-elevation myocardial infarction (STEMI). Methods and Results: Between 1995 and 2003, a total of 319 consecutive patients with acute ST-elevation myocardial infarction presenting within 6-12 hr after onset of symptoms were prospectively enrolled in a registry. Of 296 patients undergoing primary PCI, 40 patients were >= 75 years old (group A) and 256 patients younger than 75 years (group B). Elderly patients presented with a lower ejection fraction (49 +/- 14% vs. 53 +/- 13%, P = 0.046) and a higher number of cardiovascular risk factors. PCI success was achieved in 80% (group A) and 91% (group B, P = 0.031), respectively with comparable door-to-balloon times (87 49 and 95 79 min, P = ns). Periprocedural complications in both groups were low and major adverse cardiac events (death, myocardial infarction, target vessel revascularization and cardiac rehospitalization) after 6 months amounted to 23% (group A) and 20% (group B, P = ns), respectively. Conclusions: Clinical outcome of elderly patients (>= 75 years) with acute STEMI is favorable and comparable with the middle-aged population. However, procedural success was significantly lower in elderly (80%) compared to younger patients (90%). Acute percutaneous coronary intervention appears to be safe and not associated with higher periprocedural complications, in elderly patients. (C) 2007 Wiley-Liss, Inc.
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Mario Togni, Stephanie Eber, Jeannette Widmer, Michael Billinger, Peter Wenaweser, Stephane Cook, Rolf Vogel, Christian Seiler, Franz R Eberli, Willibald Maier, Roberto Corti, Marco Roffi, Thomas F Luescher, Ali Garachemani, Otto M Hess, Simon Wandel, Bernhard Meier, Peter Jueni, Stephan Windecker (2007)  Impact of vessel size on outcome after implantation of sirolimus-eluting and paclitaxel-eluting stents - A subgroup analysis of the SIRTAX trial   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 50: 12. 1123-1131 SEP 18  
Abstract: Objectives We assessed the impact of vessel size on angiographic and long-term clinical outcome after percutaneous coronary intervention (PCI) with sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) within a randomized trial (SIRTAX [Sirolimus-Eluting Stent Compared With Paclitaxel-Eluting Stent for Coronary Revascularization]). Background Percutaneous coronary intervention in small-vessel disease is associated with an increased risk of major adverse cardiac events (MACE). Methods A total of 1,012 patients were randomly assigned to treatment with SES (n = 503) or PES (n = 509). A stratified analysis of angiographic and clinical outcome was performed up to 2 years after PCI according to size of the treated vessel (reference vessel diameter <= 2.75 vs. > 2.75 mm). Results Of 1,012 patients, 370 patients (37%) with 495 lesions underwent stent implantation in small vessels only, 504 patients (50%) with 613 lesions in large vessels only, and 138 patients (14%) with 301 lesions in both small and large vessels (mixed). In patients with small-vessel stents, SES reduced MACE by 55% (10.4% vs. 21.4%; p = 0.004), mainly driven by a 69% reduction of target lesion revascularization (TLR) (6.0% vs. 17.7%; p = 0.001) compared with PES at 2 years. In patients with large- and mixed-vessel stents, rates of MACE (large: 10.4% vs. 13.1%; p = 0.33; mixed: 16.7% vs. 18.0%; p = 0.83) and TLR (large: 6.9% vs. 8.6%; p = 0.47; mixed: 16.7% vs. 15.4%; p = 0.86) were similar for SES and PES. There were no significant differences with respect to death and myocardial infarction between the 3 groups. Conclusions Compared with PES, SES more effectively reduced MACE and TLR in small-vessel disease. Differences between SES and PES appear less pronounced in patients with large- and mixed-vessel disease. (The SIRTAX trial; http:// clinicaltrials.gov/ct/show/NCT00297661?order=1; NCT00297661).
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Pascal Meier, Steffen Gloekler, Rainer Zbinden, Sarah Beckh, Stefano F de Marchi, Stephan Zbinden, Kerstin Wustmann, Michael Billinger, Rolf Vogel, Stephane Cook, Peter Wenaweser, Mario Togni, Stephan Windecker, Bernhard Meier, Christian Seiler (2007)  Beneficial effect of recruitable collaterals - A 10-year follow-up study in patients with stable coronary artery disease undergoing quantitative collateral measurements   CIRCULATION 116: 9. 975-983 AUG 28  
Abstract: Background-The prognostic relevance of the collateral circulation is still controversial. The goal of this study was to assess the impact on survival of quantitatively obtained, recruitable coronary collateral flow in patients with stable coronary artery disease during 10 years of follow-up. Methods and Results-Eight-hundred forty-five individuals ( age, 62 +/- 11 years), 106 patients without coronary artery disease and 739 patients with chronic stable coronary artery disease, underwent a total of 1053 quantitative, coronary pressure-derived collateral measurements between March 1996 and April 2006. All patients were prospectively included in a collateral flow index ( CFI) database containing information on recruitable collateral flow parameters obtained during a 1-minute coronary balloon occlusion. CFI was calculated as follows: [GRAPHICS] where P-occ1 is mean coronary occlusive pressure, P-ao is mean aortic pressure, and CVP is central venous pressure. Patients were divided into groups with poorly developed ( CFI < 0.25) or well-grown collateral vessels ( CFI >= 0.25). Follow-up information on the occurrence of all-cause mortality and major adverse cardiac events after study inclusion was collected. Cumulative 10-year survival rates in relation to all-cause deaths and cardiac deaths were 71% and 88%, respectively, in patients with low CFI and 89% and 97% in the group with high CFI (P=0.0395, P=0.0109). Through the use of Cox proportional hazards analysis, the following variables independently predicted elevated cardiac mortality: age, low CFI (as a continuous variable), and current smoking. Conclusions-A well-functioning coronary collateral circulation saves lives in patients with chronic stable coronary artery disease. Depending on the exact amount of collateral flow recruitable during a brief coronary occlusion, long-term cardiac mortality is reduced to one fourth compared with the situation without collateral supply.
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2006
Yves Allemann, Damian Hutter, Ernst Lipp, Claudio Sartori, Herve Duplain, Marc Egli, Stephane Cook, Urs Scherrer, Christian Seiler (2006)  Patent Foramen ovale and high-altitude pulmonary edema   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION 296: 24. 2954-2958 DEC 27  
Abstract: Context Individuals susceptible to high-altitude pulmonary edema ( HAPE) are characterized by exaggerated pulmonary hypertension and arterial hypoxemia at high altitude, but the underlying mechanism is incompletely understood. Anecdotal evidence suggests that shunting across a patent foramen ovale (PFO) may exacerbate hypoxemia in HAPE. Objective We hypothesized that PFO is more frequent in HAPE-susceptible individuals and may contribute to more severe arterial hypoxemia at high altitude. Design, Setting, and Participants Case-control study of 16 HAPE-susceptible participants and 19 mountaineers resistant to this condition ( repeated climbing to peaks above 4000 m and no symptoms of HAPE). Main Outcome Measures Presence of PFO determined by transesophageal echocardiography, estimated pulmonary artery pressure by Doppler echocardiography, and arterial oxygen saturation measured by pulse oximetry in HAPE-susceptible and HAPE-resistant participants at low ( 550 m) and high altitude ( 4559 m). Results The frequency of PFO was more than 4 times higher in HAPE-susceptible than in HAPE-resistant participants, both at low altitude (56% vs 11%, P=.004; odds ratio [ OR], 10.9 [95% confidence interval CI, 1.9-64.0]) and high altitude (69% vs 16%, P=. 001; OR, 11.7 [ 95% CI, 2.3-59.5]). At high altitude, mean (SD) arterial oxygen saturation prior to the onset of pulmonary edema was significantly lower in HAPE-susceptible participants than in the control group (73% [10%] vs 83% [7%], P=. 001). Moreover, in the HAPE-susceptible group, participants with a large PFO had more severe arterial hypoxemia (65% [6%] vs 77% [8%], P=. 02) than those with smaller or no PFO. Conclusions Patent foramen ovale was roughly 4 times more frequent in HAPE-susceptible mountaineers than in participants resistant to this condition. At high altitude, HAPE-susceptible participants with a large PFO had more severe hypoxemia. We speculate that at high altitude, a large PFO may contribute to exaggerated arterial hypoxemia and facilitate HAPE.
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Pascal Meier, Mario Togni, Steffen Gloekter, Stephan Windecker, Bernhard Meier, Christian Seiler (2006)  Prompt human coronary collateral vasomotor function induced by dynamic exercise   CIRCULATION 114: 18, S. OCT 31  
Abstract:
Notes: 79th Annual Scientific Session of the American-Heart-Association, Chicago, IL, NOV 12-15, 2006
R Vogel, R Zbinden, A Indermuhle, S Windecker, B Meier, C Seiler (2006)  Collateral-flow measurements in humans by myocardial contrast echocardiography : validation of coronary pressure-derived collateral-flow assessment   EUROPEAN HEART JOURNAL 27: 2. 157-165 JAN  
Abstract: Aims Myocardial blood flow (MBF) is the gold standard to assess myocardial blood supply and, as recently shown, can be obtained by myocardial contrast echocardiography (MCE). The aims of this human study are (i) to test whether measurements of collateral-derived MBF by MCE are feasible during elective angioplasty and (ii) to validate the concept of pressure-derived collateral-flow assessment. Methods and results Thirty patients with stable coronary artery disease underwent MCE of the collateral-receiving territory during and after angioplasty of 37 stenoses. MCE perfusion analysis was successful in 32 cases. MBF during and after angioplasty varied between 0.060-0.876 mL min(-1) g(-1) (0.304 +/- 0.196 mL min(-1) g(-1)) and 0.676-1.773 mL min(-1) g(-1) (1.207 +/- 0.327 mL min(-1) g(-1)), respectively. Collateral-perfusion index (CPI) is defined as the rate of MBF during and after angioplasty varied between 0.05 and 0.67 (0.26 +/- 0.15). During angioplasty, simultaneous measurements of mean aortic pressure, coronary wedge pressure, and central venous pressure determined the pressure-derived collateral-flow index (CFIp), which varied between 0.04 and 0.61 (0.23 +/- 0.14). Linear-regression analysis demonstrated an excellent agreement between CFIp and CPI (y=0.88x+0.01; r(2)=0.92; P < 0.0001). Conclusion Collateral-derived MBF measurements by MCE during angioplasty are feasible and proved that the pressure-derived CFI exactly reflects collateral relative to normal myocardial perfusion in humans.
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M Borjesson, D Assanelli, F Carre, D Dugmore, N M Panhuyzen-Goedkoop, C Seiler, J Senden, E E Solberg (2006)  ESC Study Group of Sports Cardiology : recommendations for participation in leisure-time physical activity and competitive sports for patients with ischaemic heart disease   EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION & REHABILITATION 13: 2. 137-149 APR  
Abstract: Background Evidence for the proper management of ischemic heart disease (IHD) in the general population is well established, but recommendations for physical activity and competitive sports in these patients are scarce. The aim of the present paper was to provide such recommendations to complement existing ESC and international guidelines on rehabilitation and primary/secondary prevention. Design and methods Due to the lack of studies in this field, the current recommendations are the result of consensus among experts. Sports are classified into low/moderate/high dynamic and low/moderate/high static, respectively. Results Patients with a definitive IHD and higher probability of cardiac events are not eligible for competitive sports (CS) but for individually designed leisure time physical activity (LPA); patients with definitive IHD and lower probability of cardiac events as well as those with no IHD but with a positive exercise test and high risk profile (SCORE>5%) are eligible for low/ moderate static and low dynamic (IA-IIA) sports and individually designed LPA. Patients without IHD and a high risk profile + a negative exercise-test and those with a low risk profile (SCORE<5%) are allowed all LPA and competitive sports with a few exceptions. Conclusions Individually designed LPA is possible and encouraged in patients with and without established IHD. Competitive sports may be restricted for patients with IHD, depending on the probability of cardiac events and the demands of the sport according to the current classification.
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S F De Marchi, P Meier, P Oswald, C Seiler (2006)  Variable ECG signs of ischemia during controlled occlusion of the left and right coronary artery in humans   AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 291: 1. JUL  
Abstract: Infarct size (IS) increases with vascular occlusion time, area at risk for infarction, lack of collateral supply, absence of preconditioning, and myocardial demand for O-2 supply. ECG S-T segment elevation is used as a measure of severity of ischemia and a surrogate for IS. This study in 50 patients with coronary artery disease undergoing a first 120-s balloon occlusion of a stenosis sought to determine whether S-T segment elevation, corrected for the above-mentioned variables, in the left coronary artery (LCA group, n = 36) is different from that in the right coronary artery (RCA group, n = 14) territory. After consideration of all known determinants of IS, particularly mass at risk and collateral supply, the LCA territory is more sensitive than the RCA region to a 2-min period of myocardial ischemia.
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K Wustmann, N Tomasek, O Hess, S Windecker, C Seiler, B Meier, N Walpoth (2006)  Shunt diagnostic after percutaneous PFO closure   EUROPEAN HEART JOURNAL 27: 1. AUG  
Abstract:
Notes: World Congress of Cardiology, Barcelona, SPAIN, SEP 02-06, 2006
A Indermuhle, R Vogel, P Meier, S Wirth, R Stoop, M G Mohaupt, C Seiler (2006)  The relative myocardial blood volume differentiates between hypertensive heart disease and athlete’s heart in humans   EUROPEAN HEART JOURNAL 27: 13. 1571-1578 JUL  
Abstract: Aims The adaptation of the myocardial microcirculation in humans to pathologic and physiologic stress has not been examined in vivo so far. We sought to test whether the relative blood volume (rBV) measured by myocardial contrast echocardiography (MCE) can differentiate between left ventricular (LV) hypertrophy (LVH) in hypertensive heart disease and athlete’s heart. Methods and results Four groups were investigated: hypertensive patients with LVH (n=15), semi-professional triathletes with LVH (n=15), professional football players (n=15), and sedentary control individuals without cardiovascular disease (n=15). MCE was performed at rest and during adenosine-induced hyperaemia. The rBV (mL mL(-1)), its exchange frequency (beta, min(-1)), and myocardial blood flow (mL min(-1) g(-1)) were derived from steady state and refill sequences of ultrasound contrast agent. Hypertensive patients had lower rBV (0.093 +/- 0.013 mL mL(-1)) than triathletes (0.141 +/- 0.012 mL mL(-1), P < 0.001), football players (0.129 +/- 0.014 mL mL(-1), P < 0.001), and sedentary individuals (0.126 +/- 0.018 mL mL(-1), P < 0.001). Conversely, the exchange frequency (beta) was significantly higher in hypertensive patients (11.3 +/- 3.8 min(-1)) than in triathletes (7.4 +/- 1.8 min(-1)), football players (7.7 +/- 2.3 min(-1)), and sedentary individuals (9.0 +/- 2.5 min(-1)). An rBV below 0.114 mL mL(-1) distinguished hypertensive patients and triathletes with a sensitivity of 93% and a specificity of 100%. Conclusion Pathologic and physiologic LVH were differentiated non-invasively and accurately by rBV, a measure of vascularisation assessed by MCE.
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2005
D Tuller, M Steiner, A Wahl, M Kabok, C Seiler (2005)  Systolic right ventricular function assessment by pulsed wave tissue Doppler imaging of the tricuspid annulus   SWISS MEDICAL WEEKLY 135: 31-32. 461-468 AUG 6  
Abstract: Background: Systolic right ventricular (RV) function is an important predictor in the course of various congenital and acquired heart diseases. So far, tricuspid annular motion velocity in systole as obtained by pulsed wave tissue Doppler imaging (TDI) has rarely been investigated for RV function assessment in a sizeable adult patient population. Methods: 258 individuals were included in the study. Among them, there were 107 individuals without cardiovascular disease, 71 patients with predominant RV dysfunction, 40 patients with pulmonary artery hypertension, and 40 patients with predominant left ventricular dysfunction. The reference methods for RV systolic function assessment were biplane two-dimensional echocardiography and magnetic resonance imaging (MRI; n = 3 1) for the calculation of RV ejection fraction (EF). Lateral tricuspid valve annular motion velocities in systole (TVlat, cm/s) were recorded using pulsed wave TDI from the apical 4-chamber view (long axis function). Results. RV EF as determined by biplane echocardiography correlated significantly with respective values as assessed by MRI: RVEFecho = RV EFMRI + 1.6; r(2) = 0.569, p < 0.0001. Using the best TVlat threshold of 12 cm/s, distinction between the group with RV dysfunction and the other groups was possible with 86% sensitivity and 83 % specificity. There was a direct and significant correlation between TVlat and RV ejection fraction (p < 0.000 1). Using TVlat thresholds of 12 and 9 cm/s, distinction between normal RV EF(> 55%), moderately reduced (30-55%) and severely reduced RV EF (< 30%) was possible with 84% sensitivity and 81% specificity, respectively with 83% sensitivity and 67% specificity. Conclusion: Systolic long axis velocity measurement of the lateral tricuspid annulus is useful and accurate to assess RV systolic function in a broad patient population. Thresholds of 12 and 9 cm/s allow differentiation between normal, moderately reduced and severely reduced RV ejection fraction.
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S Windecker, A Remondino, F R Eberli, P Juni, L Raber, P Wenaweser, M Togni, M Billinger, D Tuller, C Seiler, M Roffi, R Corti, G Sutsch, W Maier, T Luscher, O M Hess, M Egger, B Meier (2005)  Sirolimus-eluting and paclitaxel-eluting stents for coronary revascularization   NEW ENGLAND JOURNAL OF MEDICINE 353: 7. 653-662 AUG 18  
Abstract: Background: Sirolimus-eluting stents and paclitaxel-eluting stents, as compared with bare-metal stents, reduce the risk of restenosis. It is unclear whether there are differences in safety and efficacy between the two types of drug-eluting stents. Methods: We conducted a randomized, controlled, single-blind trial comparing sirolimus-eluting stents with paclitaxel-eluting stents in 1012 patients undergoing percutaneous coronary intervention. The primary end point was a composite of major adverse cardiac events (death from cardiac causes, myocardial infarction, and ischemia-driven revascularization of the target lesion) by nine months. Follow-up angiography was completed in 540 of 1012 patients (53.4 percent). Results: The two groups had similar baseline clinical and angiographic characteristics. The rate of major adverse cardiac events at nine months was 6.2 percent in the sirolimus-stent group and 10.8 percent in the paclitaxel-stent group (hazard ratio, 0.56; 95 percent confidence interval, 0.36 to 0.86; P=0.009). The difference was driven by a lower rate of target-lesion revascularization in the sirolimus-stent group than in the paclitaxel-stent group (4.8 percent vs. 8.3 percent; hazard ratio, 0.56; 95 percent confidence interval, 0.34 to 0.93; P=0.03). Rates of death from cardiac causes were 0.6 percent in the sirolimus-stent group and 1.6 percent in the paclitaxel-stent group (P=0.15); the rates of myocardial infarction were 2.8 percent and 3.5 percent, respectively (P=0.49); and the rates of angiographic restenosis were 6.6 percent and 11.7 percent, respectively (P=0.02). Conclusions: As compared with paclitaxel-eluting stents, the use of sirolimus-eluting stents results in fewer major adverse cardiac events, primarily by decreasing the rates of clinical and angiographic restenosis.
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P Wenaweser, C Rey, F R Eberli, M Togni, D Tuller, S Locher, A Remondino, C Seiler, O M Hess, B Meier, S Windecker (2005)  Stent thrombosis following bare-metal stent implantation : success of emergency percutaneous coronary intervention and predictors of adverse outcome   EUROPEAN HEART JOURNAL 26: 12. 1180-1187 JUN  
Abstract: Aims To investigate the efficacy and outcome of emergency percutaneous coronary interventions (PCI) in patients with stent thrombosis. Methods and results Between 1995 and 2003, 6058 patients underwent bare-metal stent implantation, of which 95 (1.6%) patients suffered from stent thrombosis. The timing of stent thrombosis was acute in 10 (11%), subacute in 61 (64%), and late in 24 (25%) patients. Procedural and clinical outcomes of emergency PCI for treatment of stent thrombosis were investigated. Emergency PCI was successful in 86 (91%), compticated by death in 2 (2%), and coronary artery bypass grafting in 2 (2%) patients. Myocardial infarction occurred in 77 (81%) patients with a peak creatine kinase level of 1466 +/- 1570 U/L. Left ventricular ejection fraction declined from 0.54 +/- 0.19 prior to 0.48 +/- 0.16 (P < 0.05) at the time of stent thrombosis after emergency PCI. A 6 month major adverse clinical events comprised death (11%), reinfarction (16%), and recurrent stent thrombosis (12%) after emergency PCI. Multivariable logistic regression analysis identified the achievement of TIMI 3 flow (OR = 0.1, CI 95% 0.01-0.54, P < 0.001) and diameter stenosis < 50% (OR = 0.06, CI 95% 0.01-0.32, P < 0.001) during emergency PCI to be independently associated with a reduced risk of cardiac death. Recurrent stent thrombosis was independently predicted by the omission of abciximab (OR = 4.3, Cl 95% 1.1-17.5). Conclusion Emergency PCI for treatment of stent thrombosis effectively restores vessel patency and flow. Patients presenting with stent thrombosis are at risk for recurrent myocardial infarction and recurrent stent thrombosis.
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R Vogel, A Inderm hle, C Seiler (2005)  Is there a minimal perfusion threshold that prevents myocardial ischaemia in humans   EUROPEAN HEART JOURNAL 26: 1. SEP  
Abstract:
Notes: 27th Congress of the European-Society-of-Cardiology, Stockholm, SWEDEN, SEP 03-07, 2005
R Zbinden, S Zbinden, M Billinger, S Windecker, B Meier, C Seiler (2005)  Influence of diabetes mellitus on coronary collateral flow : an answer to an old controversy   HEART 91: 10. 1289-1293 OCT  
Abstract: Objectives: To determine the influence of diabetes mellitus on coronary collateral flow by accurate means of collateral flow measurement in a large population with variable degrees of coronary artery disease. Methods: 200 patients (mean (SD) age 64 (9) years; 100 diabetic and 100 non-diabetic) were enrolled in the study. Coronary collateral flow was assessed in 174 stenotic and in 26 angiographically normal vessels with a pressure guidewire (n=131), Doppler guidewire (n=36), or both (n=33) to calculate pressure or flow velocity derived collateral flow index (CFI). Diabetic patients were perfectly matched with a non-diabetic control group for clinical, haemodynamic, and angiographic parameters. Results: CFI did not differ between the diabetic and the non-diabetic patients (0.21 (0.12) v 0.19 (0.13), not significant). Likewise, CFI did not differ when only angiographically normal vessels (0.20 (0.09) v 0.15 (0.08), not significant) or chronic total coronary occlusions (0.30 (0.14) v 0.30 (0.17), not significant) were compared. Fewer patients in the diabetic group tended to have angina pectoris during the one minute vessel occlusion (60 diabetic v 69 non-diabetic patients, p=0.15). Conclusion: Quantitatively measured coronary CFI did not differ between diabetic and non-diabetic patients with stable coronary artery disease.
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R Zbinden, P Meier, U Wenger, S Windecker, B Meier, C Seiler (2005)  Frequency of angina pectoris in patients with diabetes mellitus compared to non-diabetic patients : clarifying an old myth   EUROPEAN HEART JOURNAL 26: 1. SEP  
Abstract:
Notes: 27th Congress of the European-Society-of-Cardiology, Stockholm, SWEDEN, SEP 03-07, 2005
S Windecker, R D Simon, M Lins, V Klauss, F R Eberli, M Roffi, G Pedrazzini, T Moccetti, P Wenaweser, M Togni, D Tuller, R Zbinden, C Seiler, J Mehilli, A Kastrati, B Meier, O M Hess (2005)  Randomized comparison of a titanium-nitride-oxide coated stent with a stainless steel Stent for coronary revascularization   CIRCULATION 111: 20. 2617-2622 MAY 24  
Abstract: Background - Stent coating with titanium- nitride- oxide has been shown to reduce neointimal hyperplasia in the porcine restenosis model. We designed a prospective, randomized, clinical study to investigate the safety and efficacy of titanium- nitride- oxide - coated stents compared with stainless steel stents. Methods and Results - Ninety- two patients with de novo lesions were randomly assigned to treatment with titanium nitrideoxide - coated stents ( n =45) or stainless steel stents of otherwise identical design ( n = 47; control). Baseline characteristics were similar in both groups. At 30 days, no stent thromboses or other adverse events had occurred in either group. Quantitative coronary angiography at 6 months revealed lower late loss ( 0.55 +/- 0.63 versus 0.90 +/- 0.76 mm, P = 0.03) and percent diameter stenosis ( 26 +/- 17% versus 36 +/- 24%, P = 0.04) in lesions treated with titanium- nitride oxide - coated than in control stents. Binary restenosis was reduced from 33% in the control group to 15% in the titanium- nitride oxide - coated stent group ( P = 0.07). Intravascular ultrasound studies at 6 months showed smaller neointimal volume in titanium- nitride- oxide - coated stents than in control stents ( 18 +/- 21 versus 48 +/- 28 mm(3), P < 0.0001). Major adverse cardiac events at 6 months were less frequent in titanium- nitride- oxide - coated stents than in control stent - treated patients ( 7% versus 27%, P = 0.02), largely driven by a reduced need for target- lesion revascularization ( 7% versus 23%, P = 0.07). Conclusions - Revascularization with titanium- nitride- oxide - coated stents is safe and effective in patients with de novo native coronary artery lesions. Titanium- nitride- oxide - coated stents reduce restenosis and major adverse cardiac events compared with stainless steel stents of otherwise identical design.
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R D Rakhit, C Seiler, K Wustmann, S Zbinden, S Windecker, B Meier, F R Eberli (2005)  Tumour necrosis factor-alpha and interleukin-6 release during primary percutaneous coronary intervention for acute myocardial infarction is related to coronary collateral flow   CORONARY ARTERY DISEASE 16: 3. 147-152 MAY  
Abstract: Objectives We tested the hypothesis that there was an association between tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) release and measured coronary collateral flow in patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Background Tumour necrosis factor-alpha and IL-6 increase during acute myocardial infarction (AMI). However, their relation to coronary collateral flow is unknown. Methods Twelve patients with AMI due to complete thrombotic coronary occlusion underwent primary PCI within 12 h of symptom onset. Doppler-derived collateral flow index (CFI) was measured during first balloon inflation. TNF-alpha, IL-6, creatine kinase (CK), CK-MB fraction were measured from venous plasma samples serially for 24 h. Area at risk was determined off-line by coronary arteriography. Ejection fraction (EF) was measured using biplane left ventricular angiography. Results Maximal CK release varied between 569 and 6276 U/I and area at risk varied between 7 and 47% of myocardium. Tumour necrosis factor-alpha (peak 4.4 +/- 0.5 pg/ml) and IL-6 (peak 35.5 +/- 3.0 pg/ml) increased in all patients. Peak TNF-alpha and IL-6 release was independent of CK, CKMB. No minimal threshold of myocardial necrosis for cytokine expression could be detected. Similarly, TNF-alpha and IL-6 release was also independent of time to reperfusion, area at risk or EF. Using univariate regression analysis, peak TNF-alpha inversely correlated with CFI (r = 0.67, P = 0.017) whereas IL-6 positively correlated with CFI (r = 0.76, P = 0.004). Conclusions Acute myocardial infarction is associated with a significant rise in TNF-alpha and IL-6 levels independent of infarct size or myonecrosis. Tumour necrosis factor-alpha and IL-6 correlate dichotomously with CFI indicating differing roles in reperfused AML (c) 2005 Lippincott Williams & Wilkins.
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A Wahl, U Krumsdorf, B Meier, H Sievert, S Ostermayer, K Billinger, M Schwerzmann, U Becker, C Seiler, M Arnold, H P Mattle, S Windecker (2005)  Transcatheter treatment of atrial septal aneurysm associated with patent foramen ovale for prevention of recurrent paradoxical embolism in high-risk patients   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 45: 3. 377-380 FEB 1  
Abstract: OBJECTIVES This study sought to investigate the safety and efficacy of transcatheter treatment of atrial septal aneurysm (ASA) associated with patent foramen ovale (PFO). BACKGROUND Patients with both ASA and PFO are at high risk for recurrent paradoxical embolism. METHODS The procedural, echocardiographic, and clinical outcomes of 141 patients with ASA + PFO and greater than or equal to1 paradoxical embolic event undergoing transcatheter treatment were compared with 220 patients with PFO alone. RESULTS Device success (ASA + PFO, 99.3%; PFO alone, 99.5%; p = 0.75) and procedural complications (ASA + PFO, 0.7%; PFO alone, 3.2%; p = 0.12) were similar in both groups. Maximal atrial septal excursion in patients with ASA + PFO decreased from 16 +/- 4 mm before to 4 +/- 3 mm after the intervention (p < 0.0001). At 6 months follow-up, right-to-left shunt was abolished in 120 (86%) patients with ASA + PFO, compared to 187 (85%) patients with PFO alone (p = 0.80). Freedom from recurrent transient ischemic attack, stroke, and peripheral embolism at 4 years was 95% (ASA + PFO) and 94% (PFO alone, p = 0.70), respectively. A residual right-to-left shunt after the intervention was the only predictor for recurrence (hazard ratio [HR] 6.9; 95% confidence interval [CI] 1.3 to 36.9, p < 0.03) in patients with ASA + PFO. CONCLUSIONS Transcatheter treatment of ASA + PFO is safe and effective in patients with paradoxical embolism. The procedure effectively abolishes right-to-left shunt and decreases atrial septal mobility. Long-term prevention of recurrent events appears favorable when compared to patients with PFO alone. (C) 2005 by the American College of Cardiology Foundation.
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S F de Marchi, P Oswald, S Windecker, B Meier, C Seiler (2005)  Reciprocal relationship between left ventricular filling pressure and the recruitable human coronary collateral circulation   EUROPEAN HEART JOURNAL 26: 6. 558-566 MAR  
Abstract: Aims The aim of our study in patients with coronary artery disease (CAD) and present, or absent, myocardial ischaemia during coronary occlusion was to test whether (i) left ventricular (LV) filling pressure is influenced by the collateral circulation and, on the other hand, that (ii) its resistance to flow is directly associated with LV filling pressure. Methods and results In 50 patients with CAD, the following parameters were obtained before and during a 60 s balloon occlusion: LV, aortic (P-ao.) and coronary pressure (P-occl), flow velocity (V-occl), central venous pressure (CVP), and coronary flow velocity after coronary angioplasty (V&OSOL;-occl). The following variables were determined and analysed at 10s intervals during occlusion, and at 60s of occlusion: LV end-diastolic pressure (LVEDP), velocity-derived (CFIv) and pressure-derived collateral flow index (CFIp), coronary collateral (R-coll), and peripheral resistance index to flow (R-periph). Patients with ECG signs of ischaemia during coronary occlusion (insufficient collaterals, n = 33) had higher values of LVEDP over the entire course of occlusion than those without ECG signs of ischaemia during occlusion (sufficient collaterals, n = 17). Despite no ischaemia in the latter, there was an increase in LVEDP from 20 to 60 s of occlusion. In patients with insufficient collaterals, CFIv decreased and CFIP increased during occlusion. Beyond an occlusive LVEDP &GT; 27 mmHg, R-coll and Rperiph increased as a function of LVEDP. Conclusion Recruitable collaterals are reciprocally tied to LV fitting pressure during occlusion. If poorly developed, they affect it via myocardial ischaemia; if well grown, LV fitting pressure still increases gradually during occlusion despite the absence of ischaemia indicating transmission of collateral perfusion pressure to the W. With low, but not high, collateral flow, resistance to collateral as well as coronary peripheral flow is related to LV fitting pressure in the high range.
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R Vogel, A Indermuhle, J Reinhardt, P Meier, P T Siegrist, M Namdar, P A Kaufmann, C Seiler (2005)  The quantification of absolute myocardial perfusion in humans by contrast echocardiography - Algorithm and validation   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 45: 5. 754-762 MAR 1  
Abstract: OBJECTIVES We sought to test whether myocardial blood flow (MBF) can be quantified by myocardial contrast echocardiography (MCE) using a volumetric model of ultrasound contrast agent (UCA) kinetics for the description of refill curves after ultrasound-induced microsphere destruction. BACKGROUND Absolute myocardial perfusion or MBF (ml(.)min(-1.)g(-1)) is the gold standard to assess myocardial blood supply, and so far it could not be obtained by ultrasound. METHODS The volumetric model yielded MBF = rBV(.)beta/rho(T), where p, equals tissue density. The relative myocardial blood volume rBV and its exchange frequency beta were derived from UCA refill sequences. Healthy volunteers underwent MCE and positron emission tomography (PET) at rest (group I: n = 15; group II: n = 5) and during aderiosine-induced hyperemia (group II). Fifteen patients with coronary artery disease underwent simultaneous MCE and intracoronary Doppler measurements before and during intracoronary adenosine injection. RESULTS In vitro experiments confirmed the volumetric model and the reliable determination of rBV and beta for physiologic fiow velocities. In group I, 187 of 240 segments were analyzable by MCE, and a linear relation was found between MCE and PET perfusion data (y = 0.899x + 0.079; r(2) = 0.88). In group II, resting and hyperemic perfusion data showed good agreement between MCE and PET (y = 1.011x + 0.124; r(2) = 0.92). In patients, coronary stenosis varied between 0% to 89%, and myocardial perfusion reserve was in good agreement with coronary flow velocity reserve (y = 0.92x + 0.14; r(2) = 0.73). CONCLUSIONS The volumetric model of UCA kinetics allows the quantification of MBF in humans using MCE and provides the basis for the noninvasive and quantitative assessment of coronary artery disease. (C) 2005 by the American College of Cardiology Foundation.
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S Zbinden, R Zbinden, P Meier, S Windecker, C Seiler (2005)  Safety and efficacy of subcutaneous-only granulocyte-macrophage colony-stimulating factor for collateral growth promotion in patients with coronary artery disease   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 46: 9. 1636-1642 NOV 1  
Abstract: OBJECTIVES This study was designed to investigate the safety and efficacy of a short-term subcutaneous-only granulocyte-macrophage colony-stimulating factor (GM-CSF) protocol for coronary collateral growth promotion. BACKGROUND The safety and efficacy of an exclusively systemic application of GM-CSF in patients with coronary artery disease (CAD) and collateral artery promotion has not been studied so far. METHODS In 14 men (age 61 +/- 11 years) with chronic stable CAD, the effect of GM-CSF (molgramostim) on quantitatively assessed collateral flow was tested in a randomized, double-blind, placebo-controlled fashion. The study protocol consisted of an invasive collateral flow index (CFI) measurement in a stenotic as well as a normal coronary artery before and after a two-week period with subcutaneous GM-CSF (10 mu g/kg; n = 7) or placebo (n = 7). Collateral flow index was determined by simultaneous measurement of mean aortic, distal coronary occlusive, and central venous pressure. RESULTS Collateral flow index in all vessels changed from 0.116 +/- 0.05 to 0.159 +/- 0.07 in the GM-CSF group (p = 0.028) and from 0.166 +/- 0.06 to 0.166 +/- 0.04 in the placebo group (p = NS). The treatment-induced difference in CFI was +0.042 +/- 0.05 in the GM-CSF group and -0.001 +/- 0.04 in the placebo group (p = 0.035). Among 11 determined cytokines, chemokines, and their monocytic receptor concentrations, the treatment-induced change in CFI was predicted by the respective change in tumor necrosis factor-alpha concentration. Two of seven patients in the GM-CSF group and none in the placebo group suffered an acute coronary syndrome during the treatment period. CONCLUSIONS A subcutaneous-only, short-term protocol of GM-CSF is effective in promoting coronary collateral artery growth among patients with CAD. However, the drug’s safety regarding the occurrence of acute coronary syndrome is questionable.
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M Schwerzmann, K Nedeltchev, F Lagger, H P Mattle, S Windecker, B Meier, C Seiler (2005)  Prevalence and size of directly detected patent foramen ovale in migraine with aura   NEUROLOGY 65: 9. 1415-1418 NOV 8  
Abstract: Background: Transcranial contrast Doppler studies have shown an increased prevalence of right-to-left shunts in patients with migraine with aura compared with controls. The anatomy and size of these right-to-left shunts have never been directly assessed. Methods: In a cross-sectional case-control study, the authors performed transesophageal contrast echocardiography in 93 consecutive patients with migraine with aura and 93 healthy controls. Results: A patent foramen ovale was present in 44 (47% [95% CI 37 to 58%]) patients with migraine with aura and 16 (17% [95% CI 10 to 26%]) control subjects (OR 4.56 [95% CI 1.97 to 10.57]; p < 0.001). A small shunt was equally prevalent in migraineurs (10% [95% CI 5 to 18%]) and controls (10% [95% CI 5 to 18%]), but a moderate- sized or large shunt was found more often in the migraine group (38% [95% CI 28 to 48%] vs 8% [95% CI 2 to 13%] in controls; p < 0.001). The presence of more than a small shunt increased the odds of having migraine with aura 7.78-fold (95% CI 2.53 to 29.30; p < 0.001). Besides patent foramen ovale prevalence and shunt size, no other echocardiographic differences were found between the study groups. Headache and baseline characteristics did not differ in migraine patients with and without shunt. Conclusions: Nearly half of all patients with migraine with aura have a right-to-left shunt due to a patent foramen ovale. Shunt size is larger in migraineurs than controls. The clinical presentation of migraine is identical in patients with and without a patent foramen ovale.
Notes:
2004
N Kucher, B Kipfer, C Seiler, Y Allemann (2004)  Giant anastomotic Pseudoaneurysm complicating aortic xenograft replacement   ANNALS OF THORACIC SURGERY 77: 6. 2197-2199 JUN  
Abstract: A 74-year-old woman was referred for investigation of a 2-week history of progressive dyspnea. Her medical history included an aortic valve replacement with a stentless bioprosthesis followed 13 months later by the replacement of the aortic root with a porcine xenograft. Transesophageal echocardiography revealed a giant circular pseudoaneurysm of the aortic xenograft with compression of the prosthetic aortic valve and concomitant severe aortic regurgitation. Dehiscence of the proximal graft anastomosis was also diagnosed, and a possible distal anastomotic dehiscence was suspected. The latter turned out intraoperatively to be an almost complete dehiscence of the right coronary artery. The patient died intraoperatively. (C) 2004 by The Society of Thoracic Surgeons.
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S R Torti, M Billinger, M Schwerzmann, R Vogel, R Zbinden, S Windecker, C Seiler (2004)  Risk of decompression illness among 230 divers in relation to the presence and size of patent foramen ovate   EUROPEAN HEART JOURNAL 25: 12. 1014-1020 JUN  
Abstract: Background The risk of developing decompression illness (DCI) in divers with a patent foramen ovate (PFO) has not been directly determined so far; neither has it been assessed in relation to the PFO’s size. Methods In 230 scuba divers (age 39 +/- 8 years), contrast trans-oesophageal echocardiography (TEE) was performed for the detection and size grading (0-3) of PFO. Prior to TEE, the study individuals answered a detailed questionnaire about their health status and about their diving habits and accidents. For inclusion into the study, greater than or equal to200 dives and strict adherence to decompression tables were required. Results Sixty-three divers (27%) had a PFO. Overall, the absolute risk of suffering a DCI event was 2.5 per 10(4) dives. There were 18 divers (29%) with, and 10 divers (6%) without, PFO who had experienced greater than or equal to 1 major DCI events (P = 0.016). In the group with PFO, the incidence per 104 dives of a major DCI, a DO tasting longer than 24 h and of being treated in a decompression chamber amounted to 5.1 (median 0, interquartile range [IQR] 0-10.0), 1.9 (median 0, IQR 0-4.0) and 3.6 (median 0, IQR 0-9.8), respectively and was 4.8-12.9-fold higher than in the group without PFO (P < 0.001). The risk of suffering a major DCI, of a DCI tasting longer than 24 h and of being treated by recompression increased with rising PFO size. Conclusion The presence of a PFO is related to a low absolute risk of suffering five major DCI events per 104 dives, the odds of which is five times as high as in divers without PFO. The risk of suffering a major DCI parallels PFO size. (C) 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.
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M Schwerzmann, S Windecker, A Wahl, K Nedeltchev, H P Mattle, C Seiler, B Meier (2004)  Implantation of a second closure device in patients with residual shunt after percutaneous closure of patent foramen ovale   CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS 63: 4. 490-495 DEC  
Abstract: Percutaneous closure of patent foramen ovale (PFO) in patients with presumed paradoxical embolism yields complete occlusion in > 90% of patients using contemporary closure devices. Patients with a residual shunt after percutaneous PFO closure have been found at increased risk for recurrent paradoxical events. Treatment options for such patients include medical treatment using antiplatelet drugs or oral anticoagulation, surgical device removal and patch closure, and percutaneous implantation of a second closure device. We report our experience with implantation of a second closure device in 10 patients with more than a minimal residual shunt :5 6 months after percutaneous PFO closure. Procedure and fluoroscopy times were similar for the initial and repeat intervention (32 vs. 30 min and 5 vs. 6 min, respectively; P = NS). There were no procedural complications during implantation of the second closure device. Follow-up transesophageal echocardiography 6 months after the second percutaneous intervention revealed complete PFO closure in nine (90%) patients. Therefore, implantation of a second closure device in patients with persistence of more than a residual shunt after percutaneous PFO closure appears safe and effective. (C) 2004 Wiley-Liss, Inc.
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C Seiler (2004)  How should we assess patent foramen ovale?   HEART 90: 11. 1245-1247 NOV  
Abstract: Patent foramen ovale is being increasingly linked to a number of pathological conditions, most recently the prevalent disorder of migraine with aura. Many experts now no longer regard PFO as a harmless pimple but more a peril to health and even longevity
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S Windecker, A Wahl, K Nedeltchev, M Arnold, M Schwerzmann, C Seiler, H P Mattle, B Meier (2004)  Comparison of medical treatment with percutaneous closure of patent foramen ovale in patients with cryptogenic stroke   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 44: 4. 750-758 AUG 18  
Abstract: OBJECTIVES The purpose of this study was to compare the efficacy of medical treatment with percutaneous closure of patent foramen ovale (PFO). BACKGROUND Patients with cryptogenic stroke and PFO are at risk for recurrent cerebrovascular events. METHODS We compared the risk of recurrence in 308 patients with cryptogenic stroke and PFO, who were treated either medically (158 patients) or underwent percutaneous PFO closure (150 patients) between 1994 and 2000. RESULTS Patients undergoing percutaneous PFO closure had a larger right-to-left shunt (p < 0.001; 95% confidence interval [CI] 1.38 to 3.07) and were more likely to have suffered more than one cerebrovascular event (p = 0.03; 95% CI 1.04 to 2.71). At four years of follow-up, percutaneous PFO closure resulted in a non-significant trend toward risk reduction of death, stroke, or transient ischemic attack (TIA) combined (8.5% vs. 24.3%; p = 0.05; 95% CI 0.23 to 1.01), and of recurrent stroke or TIA (7.8% vs. 22.2%; p = 0.08; 95% CI 0.23 to 1.11) compared with medical treatment. Patients with more than one cerebrovascular event at baseline and those with complete occlusion of PFO were at lower risk for recurrent stroke or TIA after percutaneous PFO closure compared with medically treated patients (7.3% vs. 33.2%; p = 0.01; 95% CI 0.08 to 0.81, and 6.5% vs. 22.2%; p = 0.04; 95% CI 0.14 to 0.99, respectively). CONCLUSIONS Percutaneous PFO closure appears at least as effective as medical treatment for prevention of recurrent cerebrovascular events in cryptogenic stroke patients with PFO. It might be more effective than medical treatment in patients with complete closure and more than one cerebrovascular event. (C) 2004 by the American College of Cardiology Foundation.
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R Zbinden, M Billinger, C Seiler (2004)  Collateral vessel physiology and functional impact experimental evidence of collateral behaviour   CORONARY ARTERY DISEASE 15: 7. 389-392 NOV  
Abstract: The clinical variable predicting the development of collateral arteries in humans is the hemodynamic severity of coronary stenoses. Hyperemia induces an overall increase in coronary collateral flow in patients with coronary artery disease (CAD). There is a reduction in hyperemia-induced myocardial perfusion in the collateral-dependent vascular area in about 10% of patients with CAD and superior collateral vessels (collateral steal). Collateral recruitment has a major impact in the equation: ischemic tolerance = preconditioning + collateral recruitment. Coron Artery Dis 15:389-392 (C) 2004 Lippincott Williams Wilkins.
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R Zbinden, S Zbinden, M Billinger, S Windecker, B Meier, C Seiler (2004)  Influence of diabetes mellitus on coronary collateral flow : A definite answer to a rather elderly controversy   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 43: 5, A. MAR 3  
Abstract:
Notes: 54th Annual Scientific Session of the American-College-of-Cardiology, New Orleans, LA, MAR 07-10, 2004
Y Allemann, M Rotter, D Hutter, E Lipp, C Sartori, U Scherrer, C Seiler (2004)  Impact of acute hypoxic pulmonary hypertension on LV diastolic function in healthy mountaineers at high altitude   AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 286: 3. MAR  
Abstract: In pulmonary hypertension right ventricular pressure overload leads to abnormal left ventricular (LV) diastolic function. Acute high-altitude exposure is associated with hypoxia-induced elevation of pulmonary artery pressure particularly in the setting of high-altitude pulmonary edema. Tissue Doppler imaging (TDI) allows assessment of LV diastolic function by direct measurements of myocardial velocities independently of cardiac preload. We hypothesized that in healthy mountaineers, hypoxia-induced pulmonary artery hypertension at high altitude is quantitatively related to LV diastolic function as assessed by conventional and TDI Doppler methods. Forty-one healthy subjects (30 men and 11 women; mean age 41+/-12 yr) underwent transthoracic echocardiography at low altitude (550 m) and after a rapid ascent to high altitude (4,559 m). Measurements included the right ventricular to right atrial pressure gradient (DeltaP(RV-RA)), transmitral early (E) and late (A) diastolic flow velocities and mitral annular early (E-m) and late (A(m)) diastolic velocities obtained by TDI at four locations: septal, inferior, lateral, and anterior. At a high altitude, DeltaP(RV-RA) increased from 16+/-7 to 44+/-15 mmHg (P<0.0001), whereas the transmitral E-to-A ratio (E/A ratio) was significantly lower (1.11&PLUSMN;0.27 vs. 1.41&PLUSMN;0.35; P<0.0001) due to a significant increase of A from 52+/-15 to 65+/-16 cm/s (P=0.0001). DeltaP(RV-RA) and transmitral E/A ratio were inversely correlated (r(2)=0.16; P=0.0002) for the whole spectrum of measured values (low and high altitude). Diastolic mitral annular motion interrogation showed similar findings for spatially averaged ( four locations) as well as for the inferior and septal locations: A(m) increased from low to high altitude (all P<0.01); consequently, E-m/A(m) ratio was lower at high versus low altitude ( all P<0.01). These intraindividual changes were reflected interindividually by an inverse correlation between DeltaP(RV-RA) and E-m/A(m) (all P<0.006) and a positive association between &UDelta;PRV-RA and A(m) (all P<0.0009). In conclusion, high-altitude exposure led to a two- to threefold increase in pulmonary artery pressure in healthy mountaineers. This acute increase in pulmonary artery pressure led to a change in LV diastolic function that was directly correlated with the severity of pulmonary hypertension. However, in contrast to patients suffering from some form of cardiopulmonary disease and pulmonary hypertension, in these healthy subjects, overt LV diastolic dysfunction was not observed because it was prevented by augmented atrial contraction. We propose the new concept of compensated diastolic (dys) function.
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M Schwerzmann, S Windecker, A Wahl, H Mehta, K Nedeltchev, H Mattle, C Seiler, B Meier (2004)  Percutaneous closure of patent foramen ovale : impact of device design on safety and efficacy   HEART 90: 2. 186-190 FEB 1  
Abstract: Objective: To compare the safety and efficacy of percutaneous closure of patent foramen ovale (PFO) with the Amplatzer PFO occluder ( Amplatzer) or the PFO STAR device ( STAR) in patients with presumed paradoxical embolism. Methods: Implantation characteristics, procedural complications, residual shunt, and recurrence of thromboembolic events were recorded prospectively in 100 consecutive patients undergoing percutaneous PFO closure with the STAR (n = 50) or Amplatzer ( n = 50) devices between 1998 and 2001. The study was not randomised. Device implantation was successful in all cases. Results: There were more procedural complications in the STAR than in the Amplatzer group ( 8/50 v 1/50, p = 0.01). More than one device placement attempt was an independent predictor of procedural complications (odds ratio (OR) 8.5, 95% confidence interval (CI) 1.3 to 55.8; p = 0.03). A residual shunt six months after PFO closure, assessed by transoesophageal contrast echocardiography, occurred more often in the STAR than the Amplatzer group (17/50 v 3/50, p = 0.004), and was predicted in the STAR group by the use of a device with a 5 mm as opposed to a 3 mm disc connector ( OR 6.1, 95% CI 1.1 to 34.0; p = 0.04). The actuarial risk of recurrent thromboembolic events after 3.5 years was 16.8% ( 95% CI 7.6% to 34.6%) in the STAR and 2.7% ( 95% CI 0.4% to 17.7%) in the Amplatzer group after three years ( p = 0.08). Conclusions: Percutaneous PFO closure with the Amplatzer PFO occluder had fewer procedural complications and was more likely to be complete than with the STAR device. These findings underline the importance of device design for successful percutaneous PFO closure.
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R Vogel, A Indermuehle, P Kaufmann, C Seiler (2004)  Quantification of absolute myocardial perfusion by contrast echocardiography : Algorithm, in vitro and vivo validation   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 43: 5, A. MAR 3  
Abstract:
Notes: 54th Annual Scientific Session of the American-College-of-Cardiology, New Orleans, LA, MAR 07-10, 2004
M Schwerzmann, S Wiher, K Nedeltchev, H P Mattle, A Wahl, C Seiler, B Meier, S Windecker (2004)  Percutaneous closure of patent foramen ovale reduces the frequency of migraine attacks   NEUROLOGY 62: 8. 1399-1401 APR 27  
Abstract: Among 215 patients referred for percutaneous closure of patent foramen ovale (PFO) after presumed paradoxical embolism, we assessed the prevalence of migraine. In the year prior to PFO closure, 48 (22%) patients had migraine, twice the expected prevalence of 10 to 12% in the general European population. In patients with migraine with aura, percutaneous PFO closure reduced the frequency of migraine attacks by 54% (1.2 +/- 0.8 vs 0.6 +/- 0.8 per month; p = 0.001) and in patients with migraine without aura by 62% (1.2 +/- 0.7 vs 0.4 +/- 0.4 per month; p = 0.006). PFO closure did not have an effect on headache frequency in patients with nonmigraine headaches (1.4 +/- 0.9 vs 1.0 +/- 0.9 per month; p = NS).
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M Billinger, L Raeber, C Seiler, S Windecker, B Meier, O M Hess (2004)  Coronary collateral perfusion in patients with coronary artery disease : effect of metoprolol   EUROPEAN HEART JOURNAL 25: 7. 565-570 APR  
Abstract: Background The use of ultrathin Doppler angioplasty guidewires has made it possible to measure collateral flow quantitatively. Pharmacologic interventions have been shown to influence collateral flow and, thus, to affect myocardial ischaemia. Methods Twenty-five patients with coronary artery disease undergoing PTCA were included in the present analysis. Coronary flow velocities were measured in the ipsilateral (n = 25) and contralateral (n = 6; two Doppler wires) vessels during PTCA with and without i.v. adenosine (140 mug/kg.min) before and 3 min after 5 mg metoprolol i.v., respectively. The ipsilateral Doppler wire was positioned distal to the stenosis, whereas the distal end of the contralateral wire was in an angiographically normal vessel. The flow signals of the ipsilateral wire were used to calculate the collateral flow index (CFI). CFI was defined as the ratio of flow velocity during balloon inflation divided by resting flow. Results Heart rate and mean aortic pressure decreased slightly (ns) after i.v. metoprolol. The collateral flow index was 0.25 +/- 0.12 (one fourth of the resting coronary flow) during the first PTCA and 0.27 +/- 0.14 (ns versus first PTCA) during the second PTCA, but decreased with metoprolol to 0.16 +/- 0.08 (p < 0.0001 vs. baseline) during the third PTCA. Conclusions Coronary collateral flow increased slightly but not significantly during maximal vasodilatation with adenosine but decreased in 23 of 25 patients after i.v. metoprolol. Thus, there is a reduction in coronary collateral flow with metoprolol, probably due to an increase in coronary collateral resistance or a reduction in oxygen demand. (C) 2004 Published by Elsevier Ltd on behalf of The European Society of Cardiology.
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F S Eckstein, H Tevaearai, D Keller, J Schmidli, F F Immer, C Seiler, H Saner, T P Carrel (2004)  Early clinical experience with a new tubular equine pericardial stentless aortic valve   HEART SURGERY FORUM 7: 5.  
Abstract: Background: This study details a single-center experience with the 3F Therapeutics stentless aortic bioprosthesis (investigational device) and is part of a prospective, nonrandomized worldwide multicenter study. We assessed the implantation procedure and the valve’s efficacy in terms of early mortality and morbidity and early echocardiographic valve performance. Methods: Between June 2001 and March 2004, 24 patients (14 men/10 women) underwent aortic valve replacement (AVR) with a 3F valve. Mean age was 72 +/- 13 years (range, 31-88 years). Combined revascularization was performed in 12 patients; 1 patient received biatrial ablation therapy, 1 patient a myectomy, and 3 patients combined carotid endarterectomy. Echocardiographic systolic gradient and valve performance were investigated intra- and postoperatively by Doppler echocardiography. Results: There were 2 perioperative deaths, 1 non-valve related, due to aortic rupture in an 83-year-old woman, and 1 fatal cerebral embolism in a 77-year-old woman 5 days postoperatively. Cardiopulmonary bypass time was 102 +/- 32 minutes, aortic cross-clamp time was 79 +/- 24 minutes. Sizes for implanted 3F valves were 5 x 23 mm, 6 x 25 mm, 7 x 27 mm, and 6 x 29 mm. Follow-up systolic gradient results were 11.5 +/- 4.7 mm Hg at 30 days (n = 21), 11.4 +/- 4.5 mm Hg at 6 months (n = 18), and 13.3 +/- 4.4 mm Hg at 12 months (n = 13). During the follow-up period trivial central aortic valve regurgitation was found in 6 patients. Conclusion: The 3F aortic valve shows favorable preliminary hemodynamic results. Owing to the new valve design, implantation technique is simplified compared with other stentless valves. Anticoagulation treatment is mandatory for the first 3 months postoperatively. Long-term observation is necessary to assess life span and durability.
Notes: 10th Annual CTT Meeting, Miami Beach, FL, MAR 10-13, 2004
2003
M Schwerzmann, S Windecker, K Nedeltchev, H Mattle, A Wahl, C Seiler, B Meier (2003)  Percutaneous closure of patent foramen ovale reduces migraine frequency   EUROPEAN HEART JOURNAL 24: S. AUG  
Abstract:
Notes: Congress of the European-Society-of-Cardiology, VIENNA, AUSTRIA, AUG 30-SEP 03, 2003
M Schwerzmann, S Wiher, K Nedeltchev, H P Mattle, A Wahl, C Seiler, B Meier, S Windecker (2003)  Percutaneous closure of patent foramen ovale reduces the frequency and impact of migraine attacks   CIRCULATION 108: 17, S. 463-464 OCT 28  
Abstract:
Notes: 76th Annual Scientific Session of the American-Heart-Association, ORLANDO, FLORIDA, NOV 07-12, 2003
M Schwerzmann, K Nedeltchev, H P Mattle, L Remonda, S Windecker, B Meier, C Seiler (2003)  Presumed paradoxical embolism and migraine with aura   CIRCULATION 108: 17, S. OCT 28  
Abstract:
Notes: 76th Annual Scientific Session of the American-Heart-Association, ORLANDO, FLORIDA, NOV 07-12, 2003
M Roffi, P Wenaweser, S Windecker, H Mehta, F R Eberli, C Seiler, M Fleisch, A Garachemani, G B Pedrazzini, O M Hess, B Meier (2003)  Early exercise after coronary stenting is safe   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 42: 9. 1569-1573 NOV 5  
Abstract: OBJECTIVES In this study, we sought to assess safety of symptom-limited exercise stress tests the day after coronary stenting. BACKGROUND Isolated cases of coronary stent thrombosis have been linked to early exercise stress testing, thereby questioning the safety of unrestricted physical activity after the coronary procedure. METHODS At a single center, 1,000 patients were randomized to a symptom-limited stress test the day after coronary stenting or no stress test. The antiplatelet regimen consisted of acetylsalicylic acid and postprocedural ticlopidine or clopidogrel. The primary end point of the study was the incidence of clinical stent thrombosis at 14 days. The secondary end point was the occurrence of access site complications. RESULTS Clinical stent thrombosis occurred in five patients (1%) undergoing stress test and in five patients (1%) randomized to no stress test (p = 1.0). Access site complications were detected in 4% and 5.2% of cases, respectively (p = 0.37). CONCLUSIONS Symptom-limited exercise stress testing the day after coronary stenting does not increase the risk of clinical stent thrombosis or access site complications. Further investigations on safety of early vigorous exercise after coronary stenting in a non-supervised setting are warranted. (C) 2003 by the American College of Cardiology Foundation.
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T P Carrel, P Berdat, L Englberger, F Eckstein, F Immer, C Seiler, B Kipfer, J Schmidli (2003)  Aortic root replacement with a new stentless aortic valve xenograft conduit : Preliminary hemodynamic and clinical results   JOURNAL OF HEART VALVE DISEASE 12: 6. 752-757 NOV  
Abstract: Background and aim of the study: Beside aortic valve-sparing surgery, a composite graft,. homograft or (more rarely) an autograft are the most common options to replace a diseased or destroyed aortic root in adults. Recently, a new stentless xenograft valved conduit (Shelhigh(TM), No-React(R)) was introduced in Europe. This totally biologic conduit is glutaraldehyde cross-linked, detoxified and heparin-treated with No-React, this process eliminates residual glutaraldehyde and ensures stable tissue cross-linking. The initial clinical and hemodynamic results with this porcine valved conduit in the aortic position are presented herein. Methods: Among 308 patients who underwent thoracic aorta surgery during a 30-month period, 127 had aortic root repair or replacement. The Shelhigh stentless aortic valve conduit was implanted in 35 patients (30 males, 5 females; mean age 68 +/- 7.2 years; mean body mass index 27.5 +/- 4.1 kg/m(2)). Of these patients, 15 had aortic valve stenosis and ascending aortic aneurysm, 10 had a dilated aortic root with or without aortic regurgitation, four had acute aortic dissection type A, and six had a complex pathology (destructive endocarditis or re-do surgery). Results: One patient with prosthetic valve endocarditis died on postoperative day 1 from uncontrolled septicemia (30-day mortality, 2.7%). There were no conduit-related adverse events in the surviving patients, but one re-exploration was required for bleeding in a re-do case. Transthoracic echocardiography was available in 30 patients after six months, and in 15 patients after 12 months. The mean gradient across the aortic valve was 8.5 +/- 5.1 mmHg (range: 6 to 14 mmHg for conduit sizes 21 to 29 mm). Conclusion: The Shelhigh valved conduit shows promising hemodynamic properties. As the conduit contains no fabric or mechanical components, it is ideal for treatment of the infected aortic root, and an excellent alternative to homografts. In older patients, this conduit has the additional advantage that no long-term anticoagulation is required.
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M Schwerzmann, K Nedeltchev, H Mattle, L Remonda, G Schroth, S Windecker, B Meier, C Seiler (2003)  Patent foramen oval and ischaemic brain lesions in patients with migraine with aura   EUROPEAN HEART JOURNAL 24: S. AUG  
Abstract:
Notes: Congress of the European-Society-of-Cardiology, VIENNA, AUSTRIA, AUG 30-SEP 03, 2003
M Schwerzmann, K Nedeltchev, F Lagger, H Mattle, S Windecker, B Meier, C Seiler (2003)  Patent foramen ovale and migraine with aura   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 41: 6, A. MAR 19  
Abstract:
Notes: 52nd Annual Scientific Session of the American-College-of-Cardiology, CHICAGO, ILLINOIS, MAR 30-APR 02, 2003
H Mehta, T Chatterjee, S Windecker, F R Eberli, M Fleisch, C Seiler, O M Hess, B Meier (2003)  Four French catheters for diagnostic coronary angiography   CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS 58: 3. 275-280 MAR  
Abstract: A randomized study was conducted to assess the feasibility of 4 Fr catheters for diagnostic coronary angiograms. A total of 1,114 consecutive patients were randomized to 4 or 5 Fr catheters. Ease of use of catheters was subjectively assessed by the primary operator and the picture quality was assessed by two independent observers with a good interobserver variability (r = 0.94; P < 0.001). Predischarge local complications were recorded by the attending physician. No statistically significant difference was observed in the picture quality for the left coronary artery, right coronary artery, aorta, left ventricle, venous grafts, or renal arteries between the two groups. Fluoroscopy time (7.1 +/- 5.6 for 4 Fr vs..6.7 +/- 5.7 min for 5 Fr) and contrast quantity (140 +/- 58 vs. 144 +/- 57 ml) were comparable between the two groups. There was a statistically significant difference in favor of the 5 Fr group as regards maneuverability of catheters (93% vs. 79%; P < 0.001), and 5 Fr pigtail catheters crossed the aortic valve easier than the 4 Fr pigtail catheters (91% vs. 81%; P < 0.001). Crossover to the other catheter size or a larger sheath was more frequent with 4 Fr catheters (33/522 vs. 3/592; P < 0.001). Median time to hemostasis was 9 min for 4 Fr and 14 min for 5 Fr (P < 0.001). Of the 4 Fr patients, 84% could be mobilized at 1 hr and 86% of 5 Fr patients at 2 hr. Significant hematomas were observed in 2% with 4 Fr or 5 Fr and small hematomas in 10% and 16%, respectively (P = NS). Time to discharge was comparable in both groups (4.0 +/- 3.2 with 4 Fr vs. 4.3 +/- 3.7 hr with 5 Fr). The 4 Fr catheters are a good alternative for diagnostic coronary angiograms. The increased difficulty in maneuverability and a need for catheter changes in 70% are compensated for in part by easier hemostasis. With increasing use and finesse of these catheters, the difficulty in maneuverability are likely to be overcome.
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T Pohl, K Wustmann, S Zbinden, S Windecker, H Mehta, B Meier, C Seiler (2003)  Exercise-induced human coronary collateral function : Quantitative assessment during acute coronary occlusions   CARDIOLOGY 100: 2. 53-60  
Abstract: In 50 patients undergoing percutaneous transluminal coronary angioplasty because of chronic angina pectoris, a collateral flow index (CFI) was determined at the start and the end of two 1-min coronary occlusions, randomly accompanied by a resting state or a 3-min dynamic handgrip exercise (DHE). CFI expressing collateral flow relative to normal antegrade flow was determined by simultaneous coronary occlusive pressure, mean aortic pressure and central venous pressure measurements. When comparing CFI without and with DHE at the start as well as at the end of balloon occlusions, a significant increase was observed with DHE (overall p < 0.0001); start: 0.18 +/- 0.12 vs. 0.22 +/- 0.13, respectively (p = 0.01); end of occlusion: 0.21 +/- 0.14 vs. 0.25 +/- 0.14, respectively (p = 0.007). Copyright (C) 2003 S. Karger AG, Basel.
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K Wustmann, S Zbinden, S Windecker, B Meier, C Seiler (2003)  Is there functional collateral flow during vascular occlusion in angiographically normal coronary arteries?   CIRCULATION 107: 17. 2213-2220 MAY 6  
Abstract: Background - Thus far, it is unknown whether there is functional collateral flow through preexisting anastomoses in patients with angiographically normal coronary arteries. Such preformed coronary collateral vessels could form the basis for subsequently developing protective natural bypasses in the presence of coronary artery disease. Methods and Results - Among 100 patients, the collateral flow index (CFI) was measured in coronary arteries without stenotic lesions. The CFI was determined by simultaneous measurement of mean aortic pressure, central venous pressure, and coronary wedge pressure via a sensor-tipped guidewire at the end of a 1-minute balloon occlusion. Patients were divided in 2 groups according to complete angiographic absence ( 51 patients) or partial presence ( 49 patients) of stenotic lesions in coronary arteries other than that undergoing collateral measurement. CFI in all patients ( 61 +/- 10 years; men/women, 69/31) amounted to 0.18 +/- 0.08 ( range, 0.04 to 0.36). It showed a normal Gaussian frequency distribution; 22 individuals had a CFI greater than or equal to 0.25, a value that was empirically found to represent well-developed collaterals protective against myocardial ischemia during coronary occlusion. Accordingly, 17 patients did not reveal signs of myocardial ischemia during coronary balloon occlusion, as assessed from an intracoronary ECG, and 26 patients did not experience angina pectoris during occlusion. Conclusion - In humans with angiographically normal coronary arteries, there are functional collateral vessels to the extent that one fifth to one quarter of them do not show signs of myocardial ischemia during brief vascular occlusions.
Notes:
2002
M Billinger, R Vogel, S Gerber, M Schwerzmann, B Meier, C Seiler (2002)  A new screening method for the detection of patent foramen ovale in divers   EUROPEAN HEART JOURNAL 23: S. AUG  
Abstract:
Notes: Congress of the European-Society-of-Cardiology, BERLIN, GERMANY, AUG 31-SEP 04, 2002
S Windecker, Y Allemann, M Billinger, T Pohl, D Hutter, T Orsucci, L Blaga, B Meier, C Seiler (2002)  Effect of endurance training on coronary artery size and function in healthy men : an invasive followup study   AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 282: 6. JUN  
Abstract: In eight healthy male volunteers (cardiologists; age 36 +/- 5 yr), bicycle spiroergometry, Doppler echocardiography, and quantitative coronary angiography with intracoronary Doppler measurements before and after completion of a physical endurance exercise program of >5 mo duration were performed. Maximum oxygen uptake increased from 46 +/- 6 to 54 +/- 5 ml.kg(-1).min(-1) (P = 0.04), maximum ergometric workload changed from 3.8 +/- 0.3 to 4.4 +/- 0.3 W/kg (P = 0.001), and left ventricular mass index increased from 82 +/- 18 to 108 +/- 29 g/m(2) (P = 0.001). The right, left main, and left anterior descending coronary artery cross-sectional area increased significantly in repsonse to exercise. Before versus at the end of the exercise program, flow-induced left anterior descending coronary artery cross-sectional area was 10.1 +/- 3.5 and 11.0 +/- 3.9 mm(2), respectively (P = 0.03), nitroglycerin-induced left coronary calibers increased significantly, and coronary flow velocity reserve changed from 3.8 +/- 0.8 to 4.5 +/- 0.7 (P = 0.001). Left coronary artery correlated significantly with ventricular mass and maximum oxygen uptake, and coronary flow velocity reserve was significantly associated with maximum workload.
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R O M Netzer, S C Altwegg, E Zollinger, M Tauber, T Carrel, C Seiler (2002)  Infective endocarditis : determinants of long term outcome   HEART 88: 1. 61-66 JUL  
Abstract: Objective: To evaluate predictors of long term prognosis in infective endocarditis. Design: Retrospective cohort study. Setting: Tertiary care centre. Patients: 212 consecutive patients with infective endocarditis between 1980 and 1995 Main outcome measures: Overall and cardiac mortality; event-free survival; and the following events: recurrence, need for late valve surgery, bleeding and embolic complications, cerebral dysfunction, congestive heart failure. Results: During a mean follow up period of 89 months (range 1-244 months), 56% of patients died. In 180 hospital survivors, overall and cardiac mortality amounted to 45% and 24%, respectively. By multivariate analysis, early surgical treatment, infection by streptococci, age < 55 years, absence of congestive heart failure, and > 6 symptoms or signs of endocarditis during active infection were predictive of improved overall long term survival. Independent determinants of event-free survival were infection by streptococci and age < 55 years. Event-free survival was 17% at the end of follow up both in medically-surgically treated patients and in medically treated patients. Conclusions: Long term survival following infective endocarditis is 50% after 10 years and is predicted by early surgical treatment, age < 55 years, lack of congestive heart failure, and the initial presence of more symptoms of endocarditis.
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P Wenaweser, M Rotter, S Windecker, C Seiler, O M Hess, B Meier, F R Eberli (2002)  Is clopidogrel inferior to ticlopidine in preventing subacute stent thrombosis?   EUROPEAN HEART JOURNAL 23: S. AUG  
Abstract:
Notes: Congress of the European-Society-of-Cardiology, BERLIN, GERMANY, AUG 31-SEP 04, 2002
C Seiler, T Pohl, E Lipp, D Hutter, B Meier (2002)  Regional left ventricular function during transient coronary occlusion : relation with coronary collateral flow   HEART 88: 1. 35-42 JUL  
Abstract: Objective: To test the hypothesis that regional left ventricular (LV) function during balloon angioplasty is related to the amount of collateral flow to the ischaemic region. Design: Prospective study. Setting: Tertiary referral centre. Methods: In 50 patients with coronary artery disease and without myocardial infarction, regional systolic and diastolic LV function was determined using tissue Doppler ultrasound (TD) before and at the end of a 60 second occlusion of a stenotic lesion undergoing percutaneous transluminal coronary angioplasty (PTCA) through a pressure guidewire. The study population was subdivided into a group with collaterals insufficient (n = 33) and one with collaterals sufficient (n = 17) to prevent ECG ST shifts suggestive of myocardial ischaemia during PTCA. Pulsed TD was performed from an apical window in the myocardial region supplied by the vessel being treated by PTCA. Pressure derived collateral flow index (CFI) was determined by simultaneous measurement of mean aortic (P-ao) and distal intracoronary occlusive pressures (P-occl), where CH = (P-occl - 8)/(P-oc - 8). Results: At 60 seconds of occlusion, several parameters of systolic and diastolic TD derived LV long axis function were significantly different between the groups. Also, there was a significant correlation between regional systolic excursion velocity, early diastolic excursion velocity, regional isovolumetric relaxation time, and CFI. Conclusion: During brief coronary artery occlusions, regional systolic and diastolic LV function is directly related to the amount of collateral flow to this territory.
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P Wenaweser, M Rotter, S Windecker, C Seiler, O M Hess, B Meier, F R Eberli (2002)  The phenomenon of late stent thrombosis : Differential effect of ticlopidine and clopidogrel   CIRCULATION 106: 19, S. NOV 5  
Abstract:
Notes: American-Heart-Association Abstracts From Scientific Sessions, CHICAGO, ILLINOIS, NOV 17-20, 2002
M Billinger, P Kloos, F R Eberli, S Windecker, B Meier, C Seiler (2002)  Physiologically assessed coronary collateral flow and adverse cardiac ischemic events : A follow-up study in 403 patients with coronary artery disease   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 40: 9. 1545-1550 NOV 6  
Abstract: OBJECTIVES We sought to evaluate whether coronary collateral flow is clinically relevant for future cardiac ischemic events. BACKGROUND The link between good collateral supply related to less myocardial damage and fewer cardiac events has not been established prospectively beyond doubt. METHODS In 403 patients with stable angina pectoris undergoing percutaneous transluminal coronary angioplasty (PTCA) and quantitative collateral assessment, the occurrence of major adverse cardiac events ([MACE] cardiac death, myocardial infarction, unstable angina pectoris) and stable angina pectoris was monitored during follow-up. Collateral flow index (CFI) was determined using intracoronary pressure or Doppler guidewires. Mean aortic ([P-ao] mm Hg) and distal coronary artery occlusive pressure ([P-occ1] mm Hg) during balloon angioplasty (PTCA), or distal coronary flow velocity time integral during ([V-occl] cm) and after ([Vphi-occl] cm) PTCA were measured continuously. Pressure-derived CFI was calculated as follows: (P-occl - 5)/(P-ao - 5). Doppler-derived CFI: V-occ1/Vphi-occ1. Patients were subdivided into a group with well (CFI greater than or equal to 0.25) and poorly developed collaterals (CFI < 0.25). RESULTS Average follow-up was 94 56 (15 to 202) weeks. There were 134 patients with CFI greater than or equal to0.25 (61 +/- 11 years) and 269 with CFI <0.25 (61 - 10 years). The overall cardiac ischemic event rate (MACE and stable angina pectoris) during follow-up was 23% in patients with CFI greater than or equal to0.25 and 20% in patients with CFI <0.25 (p = NS). However, only 2.2% of patients with good collateral flow suffered a major cardiac ischemic event, compared with 9.0% among patients with poorly developed collaterals (p = 0.01). The incidence of stable angina pectoris was significantly higher in patients with well developed collaterals than in those with poorly developed collaterals (21% vs. 12%; p = 0.01). CONCLUSIONS In this relatively large population with chronic stable coronary artery disease undergoing quantitative collateral measurement, the beneficial impact of well developed collateral vessels on the occurrence of future major cardiac ischemic events is clearly demonstrated. (C) 2002 by the American College of Cardiology Foundation.
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B H Walpoth, M Menth, G Printzen, C Seiler, C Minder, T Carrel (2002)  Are serum markers a diagnostic pitfall or a reliable tool for the diagnosis of heart contusion?   INTENSIVE CARE MEDICINE 28: 1. SEP  
Abstract:
Notes: 15th Annual Congress on European-Society-of-Internsive-Care-Medicine, BARCELONA, SPAIN, SEP 29-OCT 02, 2002
N Kucher, M Schwerzmann, E Lipp, D Eyer, B Meier, C Seiler (2002)  Validation of six noninvasive Doppler methods for the assessment of left ventricular filling pressure   ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES 19: 8. 645-653 NOV  
Abstract: Objectives: The aim of this study was to determine the accuracy of six noninvasive Doppler methods for assessing invasively derived left ventricular diastolic pressure (LVDP). Background: To date, no studies have evaluated which of the various available Doppler methods are most reliable in determining LVDP in a consecutive patient population with different cardiac diseases. Methods: LVDP was estimated by the following Doppler methods (M): (1) M1-the peak mitral regurgitant flow velocity (peak MR), (2) M2-the mitral regurgitant velocity at the time of aortic valve opening (MRAVO), (3) M3-the aortic regurgitant end-diastolic flow,velocity (AR(ED)), (4) M4-the ratio of the transmitral to mitral annular early diastolic velocity (E-TM/E-DTI) (5) M5-a transmitral flow velocity regression equation (Regr(TM)), and (6) M6-the difference of pulmonary venous and transmitral A wave duration (A(PV) - A(TM) duration). For M1-M3, sphygmomanometric blood pressure was used to calculate LVDP. Results: In 101 patients, the regression coefficient, standard error of estimate, and mean difference with confidence limits between Doppler and catheter-derived measurements were as follows: M1 (n = 46): r = 0.81 (P < 0.0001), 4.3 mmHg and 3.7 +/- 12.0 mmHg; M2 (n = 47): r = 0.79 (P < 0.0001), 5.4 mmHg and 1.1 +/- 11.2 mmHg; M3 (n = 20): r = 0. 64 (P = 0.002), 7.8 mmHg and 4.6 +/- 17.6 mmHg; M4 (n = 50): r = 0.62 (P < 0.0001), 5.6 mmHg and 0 +/- 11.2 mmHg, M5 (n = 79): r = 0.24 (P = 0.03), 7.1 mmHg and - 0.1 +/- 16.8 mmHg, and M6 (n = 79): r = 0.22 (P = 0.05), 7.3 mmHg and 0 +/- 14.4 mmHg, respectively. Conclusions: The Doppler measurement of mitral regurgitant jets is most accurate method to estimate left ventricular filling pressure noninvasively.
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D Tuller, M Steiner, M Kabok, C Seiler (2002)  Assessment of systolic right ventricular function by Doppler tissue imaging of the tricuspid annulus   EUROPEAN HEART JOURNAL 23: S. AUG  
Abstract:
Notes: Congress of the European-Society-of-Cardiology, BERLIN, GERMANY, AUG 31-SEP 04, 2002
K Wustmann, S Zbinden, F R Eberli, B Meier, C Seiler (2002)  Is there collateral flow in normal coronary arteries?   EUROPEAN HEART JOURNAL 23: S. AUG  
Abstract:
Notes: Congress of the European-Society-of-Cardiology, BERLIN, GERMANY, AUG 31-SEP 04, 2002
2001
C Seiler, M Billinger, M Fleisch, B Meier (2001)  Washout collaterometry : a new method of assessing collaterals using angiographic contrast clearance during coronary occlusion   HEART 86: 5. 540-546 NOV  
Abstract: Objective To investigate the hypothesis that the time to washout of radiographic contrast medium trapped distal to an occluded collateral receiving vessel is inversely related to collateral flow, and that this provides an accurate method for characterising coronary collaterals. Methods-An intracoronary pressure derived collateral flow index was determined in 54 patients undergoing percutaneous transluminal coronary balloon angioplasty (PTCA). The study group was subdivided according to whether the collateral vessels were sufficient (n = 17) or insufficient (n = 37) to prevent ECG signs of myocardial ischaemia during PTCA. Washout collaterometry-an angiographic washout method-was carried out simultaneously; after injection of radiographic contrast medium into the collateral receiving vessel followed immediately by vascular occlusion, the number of heart beats was counted until approximately half the length of the epicardial vessel was cleared of contrast. Results-The collateral flow index was higher (0.28 (0.09) v 0.12 (0.07); p < 0.0001) and the contrast washout time shorter (8.0 (2.9) v 17.5 (6.7) heart beats; p < 0.0001) in patients with sufficient versus insufficient collaterals. There was an inverse correlation between contrast washout time and collateral flow index (r = 0.72, p < 0.0001). Washout of contrast distal to the occluded vessel within I I heart beats correctly determined sufficient and insufficient collaterals with 88% sensitivity and 81% specificity. Conclusions-Washout collaterometry is a new radiographic contrast washout method based on the inverse relation between collateral flow and the time to clearance of radiographic dye injected into the ipsilateral vessel during PTCA. It appears to be an accurate method of characterising coronary collateral vessels.
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T Pohl, C Seiler, N Billinger, E Herren, K Wustmann, H Mehta, S Windecker, F R Eberli, B Meier (2001)  Frequency distribution of collateral flow and factors influencing collateral channel development - Functional collateral channel measurement in 450 patients with coronary artery disease   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 38: 7. 1872-1878 DEC  
Abstract: Objectives We sought to determine the pathogenetic predictors of collateral channels in a large cohort of patients with coronary artery disease (CAD). Background The frequency distribution of collateral flow in patients with CAD is unknown. Only small qualitative studies have investigated which factors influence the development of collateral channels. Methods In 450 patients with one- to three-vessel CAD undergoing percutaneous transluminal coronary angioplasty (PTCA), collateral flow was measured. A collateral flow index (CFI; no unit) expressing collateral flow relative to normal anterograde flow was determined using coronary wedge pressure or Doppler measurements through sensor-tipped PTCA guide wires. frequency distribution analysis of CFI and univariate and multivariate analyses of 32 factors, including gender, age, patient history, cardiovascular risk factors, medication and coronary angiographic data, were performed. Results Two-thirds of the patients had a CFI <0.25 and <similar to>40% of patients had a CFI <0.15, but only <similar to>10% of the patients had a recruitable CFI greater than or equal to0.4. By univariate analysis, the following were predictors of CFI greater than or equal to0.25: high levels of high-density lipoprotein cholesterol, the absence of previous non-Q-wave myocardial infarction, angina pectoris during an exercise test, angiographic indicators of severe CAD and the left circumflex or right coronary artery, as the collateral-receiving vessel. Percent diameter stenosis of the lesion undergoing PTCA was the only independent predictor of a high CFI. Conclusions This large clinical study of patients with CAD in whom collateral flow was quantitatively assessed reveals that two-thirds of the patients do not have enough collateral flow to prevent myocardial ischemia during coronary occlusion, and that coronary lesion severity is the only independent pathogenetic variable related to collateral flow. (J Am Coll Cardiol 2001;38: 1872-8) (C) 2001 by the American College of Cardiology.
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C Seiler, T Pohl, K Wustmann, D Hutter, P A Nicolet, S Windecker, F R Eberli, B Meier (2001)  Promotion of collateral growth by granulocyte-macrophage colony-stimulating factor in patients with coronary artery disease - A randomized, double-blind, placebo-controlled study   CIRCULATION 104: 17. 2012-2017 OCT 23  
Abstract: Background-Experimentally, activated macrophages have been documented to induce vascular proliferation. Methods and Results-In 21 patients (age 74 +/-9 years) with extensive coronary artery disease not eligible for coronary artery bypass surgery, the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF, Molgramostim) on quantitatively assessed collateral flow was tested in a randomized, double-blind, placebo-controlled fashion. The study protocol consisted of an invasive collateral flow index (CFI) measurement immediately before intracoronary injection of 40 mug of GM-CSF (n=10) or placebo (n=11) and after a 2-week period with subcutaneous GM-CSF (10 mug/kg) or placebo, respectively. CFI was determined by simultaneous measurement of mean aortic pressure (Pao, min Hg), distal coronary occlusive pressure (P-occl, mm Hg; using intracoronary sensor guidewires), and central venous pressure (CVP, mm Hg): CFI=(P-occl-CVP)/(P-ao-CVP). CFI, expressing collateral flow during coronary occlusion relative to normal antegrade flow during vessel patency, changed from 0.21 +/-0.14 to 0.31 +/-0.23 in the GM-CSF group (P <0.05) and from 0.30 +/-0.16 to 0.23 +/-0.11 in the placebo group (P=NS). The treatment-induced difference in CFI was +0.11 +/-0.12 in the GM-CSF group and -0.07 +/-0.12 in the placebo group (P=0.01). ECG signs of myocardial ischemia during coronary balloon occlusion occurred in 9 of 10 patients before and 5 of 10 patients after GM-CSF treatment (P=0.04), whereas they were observed in 5 of 11 patients before and 8 of 11 patients after placebo (P=NS). Conclusions-This first clinical study investigating the potential of GM-CSF to improve collateral flow in patients with coronary artery disease documents its efficacy in a short-term administration protocol.
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N Kucher, E Lipp, M Schwerzmann, M Zimmerli, Y Allemann, C Seiler (2001)  Gender differences in coronary artery size per 100 g of left ventricular mass in a population without cardiac disease   SWISS MEDICAL WEEKLY 131: 41-42. 610-615 OCT 20  
Abstract: Objectives: To determine whether there is a gender difference in coronary artery size normalised for left ventricular (LV) mass. Background: Small coronary artery caliber may play a role as a risk factor for coronary artery disease in women. However, the existence of a gender difference in coronary artery size is controversial. Furthermore, coronary artery size ought to be normalised for LV mass, since there is a theoretical relation of coronary artery size to LV mass according to the law of minimum viscous energy loss for the transport of blood in the coronary circulation. Methods: In 200 individuals (100 women) without cardiac disease and with normal Doppler echocardiography, left main (LCA) and right corollary artery (RCA) size were determined using transoesophageal echocardiography. LV mass was assessed by transgastric M-mode echocardiography. Results: Age (44 +/- 15 years in women; 41 +/- 16 years in men), the presence of non-cardiac diseases, cardiovascular risk factors and medication were similar in women and men. LV mass in women was lower than in men (148 +/- 36 g, 189:145 g; p < 0.0001). LCA and RCA cross-sectional areas in women were smaller than those in men (LCA: 10 +/- 3 and 16 +/- 5 mm(2), p < 0.0001; RCA: 4 +/- 2 and 7 +/- 3 mm(2), p < 0.0001, respectively). LCA and RCA cross-sectional areas of women were smaller even after normalisation for LV mass (LCA: 7 +/- 3 and 9 +/- 3 mm(2)/100 g LV mass, p < 0.0001; RCA: 3 +/- 1 and 4 +/- 1 mm(2)/100g LV mass, p = 0.002, respectively). LCA caliber of women ranged below the theoretically expected size according to the law of minimum viscous energy loss for the transport of blood in the coronary circulation, whereas those of men tended to be above it. Conclusions: In a population without cardiac disease, women have smaller coronary artery size even after normalisation for left ventricular mass.
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A Wahl, B Meier, B Haxel, K Nedeltchev, M Arnold, E Eicher, M Sturzenegger, C Seiler, H P Mattle, S Windecker (2001)  Prognosis after percutaneous closure of patent foramen ovale for paradoxical embolism   NEUROLOGY 57: 7. 1330-1332 OCT 9  
Abstract: The long-term risk and risk factors for recurrent embolism after percutaneous closure of patent foramen ovale (PFO) were investigated in 152 consecutive patients with presumed paradoxical embolism. During follow-up, the actuarial freedom from recurrent embolism was 95.1% at 1 year, and 90.6% at 2 and 6 years. A residual shunt after percutaneous PFO closure was a predictor for recurrence (RR 5.3; 95% CI 1.3 to 21.0; p = 0.02). Randomized trials comparing medical treatment with percutaneous PFO closure in the prevention of recurrent embolism are in progress.
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A Billinger, C Seiler, M Fleisch, F R Eberli, B Meier, O M Hess (2001)  Do beta-adrenergic blocking agents increase coronary flow reserve?   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 38: 7. 1866-1871 DEC  
Abstract: Background Beta-adrenergic blocking agents are the cornerstone in the treatment of coronary artery disease (CAD). The exact pathophysiologic mechanism is not clear but depends largely on the oxygen-sparing effect of the drug, thus, the effect of metoprolol on coronary flow reserve and coronary flow velocity reserve (CFVR) was determined in patients with CAD. Methods Corona blood flow velocity was measured with the Doppler Row wire in 23 patients (age: 56 +/- 10) undergoing percutaneous transluminal coronary, angioplasty for therapeutic reasons. Measurements were carried out at rest, after 1-min vessel occlusion (postischemic CFVR) as well as after intracoronary adenosine (pharmacologic CFVR) before and after 5 mg intravenous metoprolol. In a subgroup (n=15), absolute flow was measured from coronary flow velocity multiplied by coronary cross-sectional area. Results Rate-pressure product decreased after metoprolol from 9.1 to 8.0 x 10(3) mm Hg/min (p<0.001). Pharmacologic CFVR was 2.1 at rest and increased after metoprolol to 2.7 (p=0.002). Likewise, postischemic CFVR increased from 2.6 to 3.3 (p<0.001). Postischemic CFVR was significantly higher than pharmacologic CFVR before as well as after metoprolol. Coronary vascular resistance decreased after metoprolol from 3.4 +/-2.0 to 2.3 +/-0.7 mm Hg x s/cm (p<0.02). Conclusions The following conclusions were drawn from this study. Metoprolol is associated with a significant increase in postischemic and pharmacologic MIR. However, postischemic CFVR is significantly higher than pharmacologic CFVR. The increase in CFVR by metoprolol can be explained by a reduction in vascular resistance. The increase in CFVR (=increased supply) and the reduction in oxygen consumption (= decreased demand) after metoprolol explain the beneficial effect of this beta-blocker in patients with CAD. (J Am Coll Cardiol 2001;38:1866-71) (C) 2001 by the American College of Cardiology.
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S F de Marchi, M Bodenmuller, D L Lai, C Seiler (2001)  Pulmonary venous flow velocity patterns in 404 individuals without cardiovascular disease   HEART 85: 1. 23-29 JAN  
Abstract: Objective-To determine the pulmonary venous flow velocity (PVFV) values in a large normal population. Design-Prospective study in consecutive individuals. Setting-University hospital. Methods-Among 404 normal individuals, the flow velocity pattern in the right upper pulmonary vein was recorded in 315 subjects using transthoracic echocardiography, and in both upper pulmonary veins in 100 subjects using transoesophageal echocardiography. Subjects were divided into five age groups. The PVFV values were compared between transthoracic and transoesophageal echocardiography within the age groups, and intraindividually between the right and left upper pulmonary veins in transoesophageal echocardiography. Results-Normal PVFV values for the right upper pulmonary vein in transthoracic and transoesophageal echocardiography are presented. The duration of flow reversal at atrial contraction was overestimated using transthoracic echocardiography (mean (SD): 96 (21) ms in transoesophageal echocardiography, 120 (28) ms in transthoracic echocardiography, p < 0.0001). Systolic to diastolic peak flow velocity ratio (S:D) increased earlier with advancing age with transoesophageal echocardiography than with transthoracic echocardiography. Similar results were found for the corresponding time-velocity integrals. Data from the left and right upper pulmonary veins differed with respect to onset and deceleration of flow velocities, but not for flow durations or peak velocities. Conclusions-Normal PVFV values generally show a wide range. The data presented will be of value in assessing left ventricular diastolic function and mitral regurgitation using the PVFV pattern.
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S F de Marchi, M Schwerzmann, M Fleisch, M Billinger, B Meier, C Seiler (2001)  Quantitative contrast echo cardiographic assessment of collateral derived myocardial perfusion during elective coronary angioplasty   HEART 86: 3. 324-329 SEP  
Abstract: Objective-To determine whether myocardial contrast echocardiography can be used to quantify collateral derived myocardial flow in humans. Methods-In 25 patients undergoing coronary angioplasty, a collateral flow index (CFI) was determined using intracoronary wedge pressure distal to the stenosis to be dilated, with simultaneous mean aortic pressure measurements. During balloon occlusion, echo contrast was injected into both main coronary arteries simultaneously. Echocardiography of the collateral receiving myocardial area was performed. The time course of myocardial contrast enhancement in images acquired at end diastole was quantified by measuring pixel intensities (256 grey units) within a region of interest. Perfusion variables, such as background subtracted peak pixel intensity and contrast transit rate. were obtained from a fitted gamma variate curve. Results-16 patients had a left anterior descending coronary artery stenosis, four had a left circumflex coronary artery stenosis, and five had a right coronary artery stenosis. The mean (SD) CFI was 19 (12)% (range 0-47%). Mean contrast transit rate was 11 (8) seconds. In 17 patients, a significant collateral contrast effect was observed (defined as peak pixel intensity more than the mean + 2 SD of background). Peak pixel intensity was linearly related to CFI in patients with a significant contrast effect (p = 0.002, r = 0.69) as well as in all patients (p = 0.0003, r = 0.66). Conclusions-Collateral derived perfusion of myocardial areas at risk can be demonstrated using intracoronary echo contrast injections. The peak echo contrast effect is directly related to the magnitude of collateral flow.
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S M Stengel, Y Allemann, M Zimmerli, E Lipp, N Kucher, P Mohacsi, C Seiler (2001)  Doppler tissue imaging for assessing left ventricular diastolic dysfunction in heart transplant rejection   HEART 86: 4. 432-437 OCT  
Abstract: Objective-To test the hypothesis that diastolic mitral annular motion velocity as determined by Doppler tissue imaging and left ventricular diastolic flow propagation velocity, is related to the histological degree of heart transplant rejection according to the International Society of Heart and Lung Transplantation (ISHLT). Methods-In 41 heart transplant recipients undergoing 151 myocardial biopsies, the following Doppler echocardiographic measurements were performed within one hour of biopsy: transmittal and pulmonary vein flow indices; mitral annular motion velocity indices; left ventricular diastolic flow propagation velocity. Results-Late diastolic mitral annular motion velocity (A(DTI)) and mitral annular systolic contraction velocity (SCDTI) were higher in patients with ISHLT < IIIA than in those with ISHLT greater than or equal to IIIA (A(DTI), 8.8 cm/s v 7.7 cm/s (p = 0.03); SCDTI, 19.3 cm/s v 9.3 cm/s (p < 0.05)). Sensitivity and specificity of A(DTI) < 8.7 cm/s (die best cut off value) in predicting significant heart transplant rejection were 82% and 53%, respectively. Early diastolic mitral annular motion velocity (E-DTI) and flow propagation velocity were not related to the histological degree of heart transplant rejection. Conclusions-Doppler tissue imaging of the mitral annulus is useful in diagnosing heart transplant rejection because a high late diastolic mitral annular motion velocity can reliably exclude severe rejection. However, a reduced late diastolic mitral annular motion velocity cannot predict severe rejection reliably because it is not specific enough.
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T Pohl, P Hochstrasser, M Billinger, M Fleisch, B Meier, C Seiler (2001)  Influence on collateral flow of recanalising chronic total coronary occlusions : a case-control study   HEART 86: 4. 438-443 OCT  
Abstract: Objective-To assess the effect of recanalisation on collateral flow in a case-control study in patients with and without chronic total coronary occlusions. Design In 54 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) (mean (SD) age 61 (6) years), coronary collateral flow was measured by intracoronary pressure or Doppler guide wires at the end of repeated balloon occlusions. Coronary collateral flow index (collateral flow relative to normal antegrade flow) during the first two balloon inflations in 27 patients with a chronic total occlusion (occlusion group) was compared with that of 27 patients matched for age, sex, and collateral flow index at the first occlusion and with a coronary artery diameter stenosis less than or equal to 80% (stenosis group). Results Following revascularisation, collateral flow index decreased in 17 of the patients in the occlusion group (63%) and in eight of the patients in the stenosis group (30%) (p = 0.03 between groups). The overall change of collateral flow index between the first and the second balloon occlusion was -0.04 (0.01) in the occlusion group (p = 0.07 for paired comparison; from 0.29 (0.17) to 0.25 (0.14)), and +0.02 (0.06) in the stenosis group (p = 0.06 for paired comparison; from 0.27 (0.13) to 0.30 (0.15)). The trend to collateral enhancement in the stenosis group differed significantly from the occlusion group (p = 0.01). Conclusions-While repeated coronary balloon occlusions induce collateral recruitment in the majority of patients with moderate stenoses, recanalisation of chronic total coronary occlusions is more often associated with collateral flow reduction. A later decrease in collateral flow by involution of collateral channels cannot be excluded by this study but has not been reported so far.
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M Billinger, M Fleisch, F R Eberli, B Meier, C Seiler (2001)  Collateral and collateral-adjacent hyperemic vascular resistance changes and the ipsilateral coronary flow reserve : Documentation of a mechanism causing coronary steal in patients with coronary artery disease   CARDIOVASCULAR RESEARCH 49: 3. 600-608 FEB 16  
Abstract: Objectives: The goal of this clinical study was to assess the influence of hyperemic ipsilateral, collateral and contralateral vascular resistance changes on the coronary flow velocity reserve (CFVR) of the collateral-receiving (i.e. ipsilateral) artery, and to test the validity of a model describing the development of collateral steal. Methods: In 20 patients with one- to two-vessel coronary artery disease (CAD) undergoing angioplasty of one stenotic lesion, adenosine induced intracoronary (i.c.) CFVR during vessel patency was measured using a Doppler guidewire. During stenosis occlusion, simultaneous i.c. distal ipsilateral flow velocity and pressure (P-occl, using a pressure guidewire) as well as contralateral flow velocity measurements via a third i.c. wire were performed before and during intravenous adenosine. From those measurements and simultaneous mean aortic pressure (P-ao). a collateral now index (CFI), and the ipsilateral, collateral, and contralateral vascular resistance index (R-ipsi, R-coll, R-contra) were calculated. The study population was subdivided into groups with CFI<0.15 and with CFI<greater than or equal to>0.15. Results: The percentage-diameter coronary artery stenosis (%-S) to be dilated was similar in the two groups: 78 +/- 10% versus 82 +/- 12% (NS). CFVR was not associated with %-S. In the group with CFI greater than or equal to0.15 but not with CFI<0.15, CFVR was directly and inversely associated with R-coll and R-contra, respectively. Conclusions: A hemodynamic interaction between adjacent vascular territories can be documented in patients with CAD and well developed collaterals among those regions. The CFVR of a collateralized region may, thus, be more dependent on hyperemic vascular resistance changes of the collateral and collateral-supplying area than on the ipsilateral stenosis severity, and may even fall below 1. (C) 2001 Elsevier Science B.V. All rights reserved.
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M Schwerzmann, C Seiler, E Lipp, R Guzman, K O Lovblad, M Kraus, N Kucher (2001)  Relation between directly detected patent foramen ovale and ischemic brain lesions in sport divers   ANNALS OF INTERNAL MEDICINE 134: 1. 21-24 JAN 2  
Abstract: Background: In divers, the significance of a patent foramen ovale and its potential relation to paradoxical gas emboli remain uncertain. Objective: To assess the prevalence of symptoms of decompression illness and ischemic brain lesions in divers with regard to the presence of a patent foramen ovate. Design: Retrospective cohort study. Setting: University hospital and three diving clubs in Switzerland. Participants: 52 sport divers and 52 nondiving controls. Measurements: Prevalence of self-reported decompression events, patent foramen ovale on contrast transesophageal echocardiography, and ischemic brain lesions on magnetic resonance imaging. Results: The risk for decompression illness events was 4.5-fold greater in divers with patent foramen ovate than in divers without patent foramen ovale (risk ratio, 4.5 [95% CI, 1.2 to 18.0]; P = 0,03), Among divers, 1.23 +/- 2.0 and 0.64 +/- 1.22 ischemic brain lesions per person (mean +/- SD) were detected in those with and those without patent foramen ovale, respectively. Among controls, 0.22 +/- 0.44 and 0.12 +/- 0.63 lesion per person were detected (P < 0.001 for all groups). Conclusions: Regardless of whether a diver has a patent foramen ovale, diving is associated with ischemic brain lesions.
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M Schwerzmann, C Seiler (2001)  Recreational scuba diving, patent foramen ovale and their associated risks   SWISS MEDICAL WEEKLY 131: 25-26. 365-374 JUN 30  
Abstract: Scuba diving has become a popular leisure time activity with distinct risks to health owing to its physical characteristics. Knowledge of the behaviour of any mixture of breathable gases under increased ambient pressure is crucial for safe diving and gives clues as to the pathopyhsiology of compression or decompression related disorders. Immersion in cold water augments cardiac pre- and afterload due to an increase of intrathoracic blood volume and peripheral vasoconstriction. In very rare cases, the vasoconstrictor response can lead to pulmonary oedema. Immersion of the face in cold water is associated with bradycardia mediated by increased vagal tone. In icy water, the bradycardia can be so pronounced, that syncope results. For recreational dives, compressed air (ie, 4 parts nitrogen and 1 part oxygen) is the preferred breathing gas. Its use is limited for diving to 40 to 50 m, otherwise nitrogen narcosis (â€rapture of the deepâ€) reduces a diver’s cognitive function and increases the risk of inadequate reactions. At depths of 60 to 70 m oxygen toxicity impairs respiration and at higher partial pressures also functioning of the central nervous system. The use of special nitrogen-oxygen mixtures (â€nitroxâ€, 60% nitrogen and 40% oxygen as the typical example) decreases the probability of nitrogen narcosis and probably bubble formation, at the cost of increased risk of oxygen toxicity. Most of the health hazards during dives are consequences of changes in gas volume and formation of gas bubbles due to reduction of ambient pressure during a diver’s ascent. The term barotrauma encompasses disorders related to over expansion of gas filled body cavities (mainly the lung and the inner ear). Decompression sickness results from the growth of gas nuclei in predominantly fatty tissue. Arterial gas embolism describes the penetration of such gas bubbles into the systemic circulation, either due to pulmonary barotrauma, transpulmonary passage after massive bubble formation (â€chokesâ€) or cardiac shunting. In recreational divers, neurological decompression events comprise 80% of reported cases of major decompression problems, most of the time due to pathological effects of intravascular bubbles. In divers with a history of major neurological decompression symptoms without evident cause, transoesophageal echocardiography must be performed to exclude a patent foramen ovale. If a cardiac right-to-left shunt is present, we advise divers with a history of severe decompression illness to stop diving. If they refuse to do so, it is crucial that they change their diving habits, minimising the amount of nitrogen load on the tissue. There is ongoing debate about the long term risk of scuba diving. Neuro-imaging studies revealed an increased frequency of ischaemic brain lesions in divers, which do not correlate well with subtle functional neurological deficits in experienced divers. In the light of the high prevalence of venous gas bubbles even after dives in shallow water and the presence of a cardiac right-to-left shunt in a quarter of the population (ie, patent foramen ovale), arterialisation of gas bubbles might be more frequent than usually presumed.
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S F de Marchi, M Schwerzmann, M Billinger, S Windecker, B Meier, C Seiler (2001)  Sympathetic stimulation using the cold pressor test increases coronary collateral flow   SWISS MEDICAL WEEKLY 131: 23-24. 351-356 JUN 16  
Abstract: Background: Little is known about the vasomotor function of human coronary collateral vessels. The purpose of this study was to examine collateral flow under a strong sympathetic stimulus (cold pressor test, CPT). Methods: In 30 patients (62 +/- 12 years) with coronary artery disease, two subsequent coronary artery occlusions were performed with random CPT during one of them. Two minutes before and during the 1 minute-occlusion, the patient’s hand was immerged in ice water. For the calculation of a perfusion pressure-independent collateral flow index (CFI), the aortic (P-ao), the central venous (CVP) and the coronary wedge pressure (P-occl) were measured: CFI = (P-occl- CvP) / (P-ao - CVP). Results: CPT lead to an increase in P-ao from 98 +/- 14 to 105 +/- 15 mm Hg (p = 0.002). Without and with CPT, CFI increased during occlusion from 14% +/- 10% to 16% +/- 10% (p = 0.03) and from 17% +/- 9% to 19% +/- 9% (p = 0.006), respectively, relative to normal flow. During CPT, CFI was significantly higher at the beginning as well as at the end of the occlusion compared to identical instants without CPT. CFI at the end of the control occlusion did not differ significantly from the CFI at the beginning of occlusion with CPT. Conclusions: During balloon occlusion, collateral flow increased due to collateral recruitment independent of external sympathetic stimulation. Sympathetic stimulation using CPT additionally augmented collateral flow. The collateral-flow-increasing effect of CPT is comparable to the recruitment effect of the occlusion itself. This may reflect a coronary collateral vasodilation mediated by the sympathetic nervous system.
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2000
R O M Netzer, E Zollinger, C Seiler, A Cerny (2000)  Infective endocarditis : clinical spectrum, presentation and outcome. An analysis of 212 cases 1980-1995   HEART 84: 1. 25-30 JUL  
Abstract: Objective-To evaluate recent changes in the spectrum and clinical presentation of infective endocarditis and to determine predictors of outcome. Design-A retrospective case study. Methods-Demographic, clinical, and echocardiographic characteristics were examined in 212 patients who fulfilled the Duke criteria for infective endocarditis between January 1980 and December 1995 to assess changes in clinical presentation and survival. Results-Clinical presentation and course did not change significantly during the study period despite the concurrent introduction of new diagnostic tools (for example, transoesophageal echocardiography). In-hospital mortality was 15% and remained unchanged. Neurological symptoms on admission, arthralgia, and weight loss were all independent risk factors for adverse outcome (odds ratios 26.1, 6.2, and 4.2, respectively). Age, prosthetic valve disease, previous antibiotic treatment, renal insufficiency, surgical treatment, and the type of valve involved were not predictive of mortality. In contrast to all other major reports, Streptococcus viridans was the most common causative organism in intravenous drug users (52%). Conclusions-Despite the introduction of new diagnostic tools, the course of infective endocarditis has remained unchanged over a period of 16 years. Evidence of early dissemination of the disease to other sites was associated with adverse outcome. Even in elderly patients, early aggressive treatment seems to be effective.
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P Kaufmann, C Matter, L Mandinov, J Frielingsdorf, C Seiler, O M Hess (2000)  High level of cholesterol increases coronary vasomotor tone during exercise   CORONARY ARTERY DISEASE 11: 6. 459-466 SEP  
Abstract: Background Coronary vasomotor tone plays an important role in the regulation of myocardial perfusion and influences ischemic threshold significantly, Endothelial dysfunction occurs in the presence of coronary risk factors and is closely linked to the development of atherosclerosis affecting myocardial perfusion and decreasing ischemic threshold, Objective To study the effect of hypercholesterolemia on coronary vasomotor tone in normal and stenotic coronary arteries at rest and during exercise. Patients and methods In total 48 patients were included in the present analysis. Patients were divided into two groups according to the actual levels of serum cholesterol: 18 patients had normal (mean 181 +/- 28 mg%; group 1) and 30 had elevated (mean 263 +/- 46 mg%; group 2) levels of serum cholesterol according to the 4S criteria with a cutoff level of 213 mg% (5.5 mmol/l), Coronary vasomotor tone at rest and during supine bicycle exercise was calculated by dividing mean aortic pressure by radius of coronary vessel obtained using biplanar quantitative coronary angiography, A normal as well as a stenotic vessel segment in each patient were studied. Results Normal vessel segments in patients with normal levels of cholesterol (group 1) exhibited no exercise-induced change in coronary vascular tone (+3%, NS), whereas a significant increase in tone (+24%, P < 0.01 versus rest) occurred in those with high levels of cholesterol (group 2), In contrast, stenotic segments in members of both groups exhibited an increase in vascular tone irrespective of the actual level of serum cholesterol. Conclusions Hypercholesterolemia causes a pathologic increase in coronary vasomotor tone of angiographically normal vessel segments during exercise. A similar pathologic response occurs in stenotic arteries, but this is independent of the actual level of serum cholesterol. These findings suggest that hypercholesterolemia influences vasomotor tone of the nonstenosed coronary arteries in patients with coronary artery disease probably through the occurrence of endothelial dysfunction. Coron Artery Dis 11:459-466 (C) 2000 Lippincott Williams & Wilkins.
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A Wahl, M Billinger, M Fleisch, B Meier, C Seiler (2000)  Quantitatively assessed coronary collateral circulation and restenosis following percutaneous revascularization   EUROPEAN HEART JOURNAL 21: 21. 1776-1784 NOV  
Abstract: Aims A high degree of collateral supply to a vascular area where a percutaneous transluminal coronary angioplasty (PTCA) has been performed represents a haemodynamic force competing with the antegrade flow through the dilated lesion. Therefore, our purpose was to determine whether patients with restenosis following PTCA have a higher collateral flow to the recipient vessel than patients without restenosis. Methods and Results In 200 consecutive PTCA patients, an intracoronary pressure-derived collateral Row index (CFI) was determined quantitatively during balloon occlusion, using simultaneous measurements of the mean aortic pressure (P-ao) and of the intracoronary pressure distal to the occluded stenosis (P-occl), as well as the estimated central venous pressure (CVP=5 mmHg): CFI=(P-occl-CVP)/(P-ao-CVP). Sixty-four patients had an angiographic follow-up examination after at least 2 months, and were subdivided into patients with restenosis (>50% diameter stenosis, n=34) and patients without restenosis (n=30). Patients with restenosis had a significantly higher collateral how index at the initial coronary angiography than patients without restenosis (0.26 +/- 0.14 vs 0.12 +/- 0.09: P<0.0001). Conclusions Patients with restenosis after PTCA show a more extended collateral supply to this recipient area than patients without restenosis. Well developed collaterals to a revascularized region are a risk factor for restenosis of the treated lesion. (Eur Heart J 2000; 21: 1776-1784, doi:10.1053/euhj.2000. 2129) (C) 2000 The European Society of Cardiology.
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S Windecker, A Wahl, T Chatterjee, A Garachemani, F R Eberli, C Seiler, B Meier (2000)  Percutaneous closure of patent foramen ovale in patients with paradoxical embolism - Long-term risk of recurrent thromboembolic events   CIRCULATION 101: 8. 893-898 FEB 29  
Abstract: Background-Patients with a patent foramen ovale (PFO) and paradoxical embolism are at risk for recurrent thromboembolic events. This study investigated the long-term risk of recurrent thromboembolic events in patients with PFO and paradoxical embolism after percutaneous PFO closure. Methods and Results Since 1994, a total of 80 patients with PFO and at least 1 paradoxical embolic event (transient ischemic attack [TIA], cerebrovascular accident [CVA], peripheral embolism) have undergone percutaneous PFO closure with 5 different devices. There were 30 women and 50 men, with a mean age of 52 +/- 12 years. Sixty patients had only a PFO, whereas 20 patients had both a PFO and an atrial septal aneurysm. The implantation procedure was successful in 78 patients (98%). During 5 years of follow-up (mean, 1.6 +/- 1.4 years; range, 0.1 to 5.0 years), the actuarial annual risk to suffer a recurrent thromboembolic event was 2.5% for TIA, 0% for CVA, 0.9% for peripheral emboli, and 3.4% for the combined end point of TIA, CVA, or peripheral embolism. A postprocedural shunt was a predictor of recurrent paradoxical embolism (RR, 4.2; 95% CI, 1.1 to 17.81 P=0.03). The risk for recurrent thromboembolic events in patients with both atrial septal aneurysm and PFO was not significantly increased compared with patients with only PFO (RR, 1.0; 95% CI, 0.2 to 4.7; P=0.95). Conclusions-Percutaneous PFO closure appears to be a promising technique in the prevention of recurrent systemic thromboembolism in patients with a PFO after a first event. Prospective studies comparing percutaneous PFO closure with antithrombotic medications or surgery must define its therapeutic value.
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L Mandinov, F R Eberli, C Seiler, O M Hess (2000)  Diastolic heart failure   CARDIOVASCULAR RESEARCH 45: 4. 813-825 MAR  
Abstract: Primary diastolic failure is typically seen in patients with hypertensive or valvular heart disease as well as in hypertrophic or restrictive cardiomyopathy but can also occur in a variety of clinical disorders, especially tachycardia and ischemia. Diastolic dysfunction has a particularly high prevalence in elderly patients and is generally associated, with low mortality but high morbidity. The pathophysiology of diastolic dysfunction includes delayed relaxation, impaired LV filling and/or increased stiffness. These conditions result typically in an upward displacement of the diastolic pressure-volume relationship with increased end-diastolic, left atrial and pulmo-capillary wedge pressure leading to symptoms of pulmonary congestion. Diagnosis of diastolic heart failure requires three conditions: (1) presence of signs or symptoms of heart failure; (2) presence of normal or slightly reduced LV ejection fraction (EF>50%) and (3) presence of increased diastolic filling pressure. Assessment of diastolic function can be performed with several non-invasive (2D- and Doppler-echocardiography, color Doppler M-mode, Doppler tissue imaging, MR-myocardial tagging, radionuclide ventriculography) and invasive techniques (micromanometry, angiography, conductance method). Doppler-echocardiography is the most useful tool to routinely measure diastolic function. Different techniques can be used alone or in combination to assess LV diastolic function, but most of them are dependent on heart rate, pre- and afterload. The transmitral flow pattern remains the starting point, since it is easy to acquire and rapidly categorizes patients into normal (E > A), delayed relaxation (E < A), and restrictive (E much greater than A) filling patterns. Invasive assessment of diastolic function allows determination of the time constant of relaxation from the exponential pressure decay during isovolumic relaxation, and the evaluation of the passive elastic properties from the slope of the diastolic pressure-volume (=constant of chamber stiffness) and stress-strain relationship (= constant of myocardial stiffness). The prognosis of diastolic heart failure is usually better than for systolic dysfunction. Diastolic heart failure is associated with a lower annual mortality rate of approximately 8% as compared to annual mortality of 19% in heart failure with systolic dysfunction, however, morbidity rate can be substantial. Thus, diastolic heart failure is an important clinical disorder mainly seen in the elderly patients with hypertensive heart disease. Early recognition and appropriate therapy of diastolic dysfunction is advisable to prevent further progression to diastolic heart failure and death. There is no specific therapy to improve LV diastolic function directly. Medical therapy of diastolic dysfunction is often empirical and lacks clear-cut pathophysiologic concepts. Nevertheless, there is growing evidence that calcium channel blockers, beta-blockers, ACE-inhibitors and AT2-blockers as well as nitric oxide donors can be beneficial. Treatment of the underlying disease is currently the most important therapeutic approach. (C) 2000 Published by Elsevier Science B.V. All rights reserved.
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W Maier, F Cosentino, R B Lutolf, M Fleisch, C Seiler, O M Hess, B Meier, T F Luscher (2000)  Tetrahydrobiopterin improves endothelial function in patients with coronary artery disease   JOURNAL OF CARDIOVASCULAR PHARMACOLOGY 35: 2. 173-178 FEB  
Abstract: Tetrahydrobiopterin (BH(4)) is an essential cofactor for nitric oxide:synthase (NOS) and a scavenger of oxygen-derived free radicals. Decreased availability of BH(4) leads, under in vitro conditions, to reduced nitric oxide (NO) production and increased superoxide formation. We studied the effect of exogenous BH(4) on endothelial function of angiographically normal vessel segments in patients with coronary artery disease. Nineteen patients with coronary artery disease underwent quantitative coronary angiography with simultaneous coronary now velocity measurements (Cardiometrics FloWire). Data were obtained in angiographically normal segments of the left coronary artery at baseline, after intracoronary (i.c.) administration of acetylcholine (Ach; 10(-4) M), after infusion of BH(4) (10(-2) M), and after co-infusion of ACh and BH(4). At the end of the study, 300 mu g nitroglycerin (NTG) i.c. was administered to obtain maximal vasodilation. At each step, flow velocity was determined before and after 18 mu g adenosine i.c. to assess coronary flow velocity reserve. In 15 patients, ACh induced coronary vasoconstriction of -18 +/- 3% (endothelial dysfunction; p < 0.0001 vs. baseline), and in four patients, vasodilation of +39 +/- 20%. In the 15 patients with endothelial dysfunction, BH(4) alone did not influence vessel area but prevented vasoconstriction to ACh (+2 +/- 3%, NS, vs. baseline). Correspondingly, calculated volume flow showed the highest value after co-infusion of ACh and BH(4). Coronary flow velocity reserve was comparable during the various infusion steps. BH(4) pre vents ACh-induced vasoconstriction of angiographically normal vessels in patients with coronary artery disease. Thus substitution of this cofactor of NOS may represent a new approach for the treatment of endothelial dysfunction.
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T Chatterjee, S Windecker, J P Pfammatter, C Seiler, B Meier (2000)  Non-surgical closure of patent ductus arteriosus : acute and long-term results   SCHWEIZERISCHE MEDIZINISCHE WOCHENSCHRIFT 130: 18. 664-670 MAY 6  
Abstract: Introduction: Closure of a patent ductus arteriosus (PDA) even with small shunt volumes in asymptomatic patients is recommended because of the risk of endocarditis (1.5% per gear) and the potential development of congestive heart failure or pulmonary hypertension. Methods: 16 patients (9 adults [5 men /4 women] and 7 children [3 boys / 4 girls]) underwent transcatheter closure of a PDA. The intervention was performed using the Rashkind umbrella in 12 cases, the Amplatzer duct occluder in 2 cases, a coil in 2 cases, and the Sideris self-adjusting device in one case. Echocardiographic controls were carried out one day, 6 months, 12 months and 24 months Lifter the intervention. Results: PDA closure was complete immediately following the intervention ill 9 of 16 patients (56%). At follow-up (mean 19 months) complete closure was observed in 14 of 16 patients (87%). All residual shunts were trivial. The complete closure tate in adults was 100% and in children 71%. Complications such as device embolism, endarteritis and haemolysis did not occur. Conclusion: Non-surgical closure of a PDA is a safe and effective technique.
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P A Kaufmann, L Mandinov, C Seiler, O M Hess (2000)  Impact of exercise-induced coronary vasomotion on anti-ischemic therapy   CORONARY ARTERY DISEASE 11: 4. 363-369 JUN  
Abstract: Coronary vasomotion has an important role in the regulation of myocardial perfusion. During dynamic exercise, normal coronary arteries dilate, whereas stenotic arteries constrict. This exercise-induced vasoconstriction has been associated with the occurrence of myocardial ischemia and has been believed to be the result of endothelial dysfunction, with a reduced release or production of EDRF, increased sympathetic stimulation, enhanced platelet aggregation with release of thromboxane A(2) and serotonin, or a passive collapse of the disease-free wall segment within the stenosis (the Bernoulli effect), or a combination of any of these. More recently, it has been realized that pharmacological treatment might prevent exercise-induced vasoconstriction and, thus, reduce myocardial ischemia and the occurrence of angina pectoris. Vasodilators such as nitrates, calcium antagonists or alpha-receptor blockers dilate the coronary arteries and prevent coronary stenosis narrowing during exercise. In contrast, beta-blocking agents are associated with coronary vasoconstriction at rest, but - conversely - can induce coronary vasodilatation during exercise. Pharmacological treatment in patients with stable angina pectoris may improve myocardial ischemia by reducing pre- and afterload, myocardial contractility, oxygen consumption, and vasomotor tone. However, coronary collateral perfusion can modify these effects by shunting blood from the non-ischemic to the ischemic region (collateral flow) or by shunting blood from the ischemic to the non-ischemic zone (coronary steal phenomenon). Typically, a steal phenomenon has been reported in patients receiving either dipyridamole or calcium antagonists, whereas a reversed steal has been described after beta-blockade, with an increase in contralateral tone shunting blood from the non-ischemic to the ischemic zone (reverse steal phenomenon). Coron Artery Dis 11:363-369 (C) 2000 Lippincott Williams & Wilkins.
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S F De Marchi, Y Allemann, C Seiler (2000)  Relaxation in hypertrophic cardiomyopathy and hypertensive heart disease : relations between hypertrophy and diastolic function   HEART 83: 6. 678-684 JUN  
Abstract: Aim-To determine the relation between the extent and distribution of left ventricular hypertrophy and the degree of disturbance of regional relaxation and global left ventricular filling. Methods-Regional wall thickness (rWT) was measured in eight myocardial regions in 17 patients with hypertrophic cardiomyopathy, 12 patients with hypertensive heart disease, and 10 age matched normal subjects, and an asymmetry index calculated. Regional relaxation was assessed in these eight regions using regional isovolumetric relaxation time (rIVRT) and early to late peak filling velocity ratio (rE/A) derived from Doppler tissue imaging. Asynchrony of rIVRT was calculated. Doppler left ventricular filling indices were assessed using the isovolumetric relaxation time, the deceleration time of early diastolic filling (E-DT), and the E/A ratio. Results-There was a correlation between rWT and both rIVRT and rE/A in the two types of heart disease (hypertrophic cardiomyopathy: r = 0.47, p < 0.0001 for rIVRT; r -0.20, p < 0.05 for rE/A; hypertensive heart disease: r = 0.21, p < 0.05 for rIVRT; r = -0.30, p = 0.003 for rE/A). The degree of left ventricular asymmetry was related to prolonged E-DT (r = 0.50, p = 0.001) and increased asynchrony (r = 0.42, p = 0.002) in all patients combined, but not within individual groups. Asynchrony itself was associated with decreased EIA (r = -0.39, p = 0.01) and protracted E-DT (r = 0.69, p < 0.0001) and isovolumetric relaxation time (r = 0.51, p = 0.001) in all patients. These correlations were still significant for E-DT in hypertrophic cardiomyopathy (r = 0.56, p = 0.02) and hypertensive heart disease (r = 0.59, p < 0.05) and for isovolumetric relaxation time in non-obstructive hypertrophic cardiomyopathy (n = 8, r = 0.87, p = 0.005). Conclusions-Non-invasive ultrasonographic examination of the left ventricle shows that in both hypertrophic cardiomyopathy and hypertensive heart disease, the local extent of left ventricular hypertrophy is associated with regional left ventricular relaxation abnormalities. Asymmetrical distribution of left ventricular hypertrophy is indirectly related to global left ventricular early filling abnormalities through regional asynchrony of left ventricular relaxation.
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1999
M Fleisch, M Billinger, F R Eberli, A R Garachemani, B Meier, C Seiler (1999)  Physiologically assessed coronary collateral flow and intracoronary growth factor concentrations in patients with 1-to 3-vessel coronary artery disease   CIRCULATION 100: 19. 1945-1950 NOV 9  
Abstract: Background-The purpose of this study was to test the hypothesis that there is a relation between collateral flow and intracoronary concentrations of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) and that the combined concentrations of both growth factors and the extent of coronary artery disease (CAD) play a role as covariables in such an association. Methods and Results-In 76 patients undergoing balloon angioplasty, a collateral flow index (CFI, no units) was determined with sensor-tipped guidewires. Simultaneously, serum concentrations of bFGF and VEGF, obtained at the aortic root from the ostium of the collateralized coronary artery (n = 76) and from the distal position of the occluded coronary artery (n = 34), were determined. There was a direct correlation between CFI and distal VEGF (r = 0.33, P = 0.05) but not bFGF concentrations. Focusing on the proximal sampling site, there was a direct correlation between CFI and both bFGF (r = 0.29, P = 0.01) and VEGF concentrations (r = 0.44, P < 0.0001). The sum of the concentrations of both growth factors was directly associated with CFI irrespective of the proximal (r = 0.51, P < 0.0001) or distal sampling site (r = 0.34, P = 0.048). There was a trend toward higher proximal VEGF concentrations in patients with higher numbers of coronary stenotic lesions (r = 0.25, P = 0.03). Conclusions-In patients with CAD, there is an association between a directly measured index of collateral flow and intracoronary concentrations of bFGF and VEGF. This direct relation is dependent on the site of blood sampling within the coronary artery tree. The association is closest when the combined bFGF and VEGF concentrations are taken into account. In the case of VEGF, it is influenced by the degree of coronary atherosclerosis.
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C Seiler, M Fleisch, M Billinger, B Meier (1999)  Simultaneous intracoronary velocity- and pressure-derived assessment of adenosine-induced collateral hemodynamics in patients with one- to two-vessel coronary artery disease   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 34: 7. 1985-1994 DEC  
Abstract: OBJECTIVES The purpose of this investigation in patients with poorly and well developed coronary collaterals was to assess the influence of collateral and collateral adjacent vascular resistances and, in part, a stenotic lesion of the collateral supplying vessel on the hemodynamic collateral responses to adenosine. BACKGROUND In humans, little is known about the functional behavior of the coronary collateral circulation. METHODS In 50 patients with one- and two-vessel coronary artery disease (CAD) undergoing percutaneous transluminal coronary angioplasty (PTCA), collateral flow index (CFI, no unit) changes and vascular resistance index (R, cm/mm Hg) changes of the collateral (R-coll) and the distal collateral receiving (R-4) vessel in response to adenosine (140 mu g/min/kg ITT) were measured by intracoronary (i.c.) Doppler and pressure guidewires. The variables were determined at baseline and during adenosine in patients with poor (angiographic collateral degree before PTCA <2 of 0 to 3) and good coronary collaterals. RESULTS Pressure-derived CFI (CFI,) decreased under adenosine in patients with poor collaterals, and it increased in the group with good collaterals. There were inverse correlations between the adenosine-induced change in CFIp and the change in R-coll (r = 0.61, p = 0.0001). In the group with good, but not with poor collaterals, there was also a significant correlation between CFIp increase and the decrease in R-4, between the severity of the contralateral stenosis and CFIp augmentation and among the left versus right coronary artery as ipsilateral vessel and CFIp change. CONCLUSIONS Overall, patients with well, versus poorly developed coronary collaterals do better regarding the capacity to increase collateral flow in response to adenosine, In patients with good, but not poor, collaterals, an adenosine-induced collateral flow increase depends on the ipsilateral distal vascular resistance decrease, but is also directly influenced by the severity of a contralateral stenosis and probably by the size of the collateralized vascular bed. (C) 1999 by the American College of Cardiology.
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S F de Marchi, S Windecker, B C Aeschbacher, C Seiler (1999)  Influence of left ventricular relaxation on the pressure half time of aortic regurgitation   HEART 82: 5. 607-613 NOV  
Abstract: Background-The severity of aortic regurgitation can be estimated using pressure half time (PHT) of the aortic regurgitation flow velocity, but the correlation between regurgitant fraction and PHT is weak. Aim-To test the hypothesis that the association between PHT and regurgitant fraction is substantially influenced by left ventricular relaxation. Methods-In 63 patients with aortic regurgitation, subdivided into a group without (n = 22) and a group with (n = 41) left ventricular hypertrophy, regurgitant fraction was calculated using the difference between right and left ventricular cardiac outputs. Left ventricular relaxation was assessed using the early to late diastolic Doppler tissue velocity ratio of the mitral annulus (E/ADTI), the E/A ratio of mitral inflow (E/AM), and the E deceleration time (E-DT). Left ventricular hypertrophy was assessed using the M mode derived left ventricular mass index. Results-The overall correlation between regurgitant fraction and PHT was weak (r = 0.36, p < 0.005). In patients without left ventricular hypertrophy, there was a significant correlation between regurgitant fraction and PHT (r = 0.62, p < 0.005), but not in patients with left ventricular hypertrophy. In patients with a left ventricular relaxation abnormality (defined as E/ADTI< 1, E/AM< age corrected lower limit, E-DT greater than or equal to 220 ms), no associations between regurgitant fraction and PHT were found, whereas in patients without left ventricular relaxation abnormalities, the regurgitant fraction to PHT relations were significant (normal E/AM: r = 0.57, p = 0.02; E-DT< 220 ms: r = 0.50, p < 0.001; E/ADTI < 1: r = 0.57, p = 0.02). Conclusions-Only normal left ventricular relaxation allows a significant decay of PHT with increasing aortic regurgitation severity. In abnormal relaxation, which is usually present in left ventricular hypertrophy, wide variation in prolonged backward left ventricular filling may cause dissociation between the regurgitant fraction and PHT. Thus the PHT method should only be used in the absence of left ventricular relaxation abnormalities.
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M Billinger, M Fleisch, F R Eberli, A Garachemani, B Meier, C Seiler (1999)  Is the development of myocardial tolerance to repeated ischemia in humans due to preconditioning or to collateral recruitment?   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 33: 4. 1027-1035 MAR 15  
Abstract: OBJECTIVES The purpose of this study in patients with quantitatively determined, poorly developed coronary collaterals was to assess the contribution of ischemic as well as adenosine-induced preconditioning and of collateral recruitment to the development of tolerance against repetitive myocardial ischemia. BACKGROUND The development of myocardial tolerance to repeated ischemia is nowadays interpreted to be due to biochemical adaptation (i.e., ischemic preconditioning). METHODS In 30 patients undergoing percutaneous transluminal coronary angioplasty, myocardial adaptation to ischemia was measured using intracoronary (i.c.) electrocardiogaphic (ECG) ST segment elevation changes obtained from a 0.014-in. (0.036 cm) pressure guidewire positioned distal to the stenosis during three subsequent 2-min balloon occlusions. Simultaneously, an i.c. pressure-derived collateral flow index (CFI, no unit) was determined as the ratio between distal occlusive minus central venous pressure divided by the mean aortic minus central venous pressure. The study patients were divided into two groups according to the pretreatment with i.c. adenosine (2.4 mg/min for 10 min starting 20 min before the first occlusion, n = 15) or with normal saline (control group, n = 15). RESULTS Collateral flow index at the first occlusion was not different between the groups (0.15 +/- 0.10 in the adenosine group and 0.13 +/- 0.11 in the control group, p = NS), and it increased significantly and similarly to 0.20 +/- 0.14 and to 0.19 +/- 0.10, respectively (p < 0.01) during the third occlusion. The i.c. ECG ST elevation (normalized for the QRS amplitude) was not different between the two groups at the first occlusion (0.25 +/- 0.13 in the adenosine group, 0.25 +/- 0.19 in the control group). It decreased significantly during subsequent coronary occlusions to 0.20 +/- 0.15 and to 0.17 +/- 0.13, respectively. There was a correlation between the change in CFI (first to third occlusion; Delta CFI) and the respective ST elevation shift (Delta ST): Delta ST = -0.02 to 0.78 x Delta CFI; r = 0.54, p = 0.02. CONCLUSION Even in patients with few coronary collaterals, the myocardial adaptation to repetitive ischemia is closely related to collateral recruitment. Pharmacologic preconditioning using a treatment with i.c. adenosine before angioplasty does not occur. The variable responses of ECG signs of ischemic adaptation to collateral channel opening suggest that ischemic preconditioning is a relevant factor in the development of ischemic tolerance. (J Am Coll Cardiol 1999;33:1027-35) (C) 1999 by the American College of Cardiology.
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1998
P A Kaufmann, J Frielingsdorf, L Mandinov, C Seiler, R Hug, O M Hess (1998)  Reversal of abnormal coronary vasomotion by calcium antagonists in patients with hypercholesterolemia   CIRCULATION 97: 14. 1348-1354 APR 14  
Abstract: Background-It has been shown that exercise-induced coronary vasodilation of angiographically normal coronary vessels is reduced in hypercholesterolemic patients. The purpose of this study was to evaluate the effect of calcium channel blockers on coronary vasomotion of angiographically smooth coronary arteries in hypercholesterolemic patients. Methods and Results-A total of 57 patients were included in the present analysis. Vasomotion of angiographically normal coronary arteries was evaluated in 37 control subjects (group 1) without and 20 patients (group 2) with calcium blocker administration before physical exercise. Both groups were subdivided into subgroup A (normal cholesterol values: less than or equal to 5.5 mmol/L or 212 mg%) and subgroup B (elevated cholesterol values: >5.5 mmol/L or 212 mg%). Coronary luminal area at rest and during exercise was assessed by biplane quantitative coronary angiography. The normal vessels showed a significant increase in coronary luminal area during exercise in subgroup A (n=13) with normal cholesterol values (31%; P<.05) but not in subgroup B (n=24; 13%; P=NS). In contrast, all patients in group 2 showed similar vasodilation during exercise, namely, 22% (P<.05) in subgroups A (n=8) and B (n=12) (P<.05). Independent of the actual cholesterol level, the stenotic lesions showed coronary vasoconstriction during exercise in group 1 but vasodilation in group 2 after pretreatment with calcium antagonists. Conclusions-Coronary vasomotor response to exercise is inversely related to actual serum cholesterol level in angiographically normal vessels. Administration of calcium antagonists normalizes exercise-induced vasodilation and thus eliminates cholesterol-induced abnormal vasomotion, probably by a direct effect on the smooth muscles of the vasculature.
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C Seiler, B C Aeschbacher, B Meier (1998)  Quantitation of mitral regurgitation using the systolic/diastolic pulmonary venous flow velocity ratio   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 31: 6. 1383-1390 MAY  
Abstract: Objectives. The purpose of this study was to test the hypothesis that pulmonary venous flow velocity ratios during systole and diastole in patients with mitral regurgitation (MR) correctly predict the quantitative degree of MR. Background. Pulmonary venous how velocity measurements have thus far been used only for the qualitative assessment of MR. Recent studies have evaluated this method using transesophageal echocardiography against semiquantitative references. Methods. In 100 patients without aortic regurgitation or atrial fibrillation and with left ventricular (LV) ejection fraction > 45%, MR was assessed by quantitative echocardiographic Doppler and color Doppler, providing forward and total LV stroke volume for the calculation of the mitral regurgitant fraction (RFstandard), the reference parameter, and also supplying mitral regurgitant orifice area (ROA) values and the RF by the how convergence method (RFPISA [proximal isovelocity surface areal]). Measurements of pulmonary venous flow velocity time integral values during systole to diastole (VTIs/VTId) were obtained and tested for their predictability of ROA, RFstandard and RFPISA. R esults. There was an inverse and significant correlation between VTIs/VTId and ROA, RFPISA and RFstandard, respectively: RFstandard = 49 -20 VTIs/VTId, r = 0.77, p = 0.0001. A principal source of variability in the relation between VTIs/VTId and RFstandard was the presence of mitral valve prolapse as the cause of MR. Pulmonary venous flow reversal (VTIs/VTId < 0) correctly identified severe MR with 52% sensitivity, 96% specificity and 80% positive and 87% negative predictive accuracy. Conclusions. The VTIs/VTId ratio allows a moderately accurate assessment of the severity of MR. (C) 1998 by the American College of Cardiology.
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M Roffi, S F de Marchi, C Seiler (1998)  Congenitally corrected transposition of the great arteries in an 80 year old woman   HEART 79: 6. 622-623 JUN  
Abstract: Congenitally corrected transposition of the great arteries (CCTGA) is a rare form of congenital heart disease characterised by atrioventricular as well as ventriculoarterial discordance. It is usually associated with a variety of severe intracardiac defects. Few patients with this abnormality survive past 50 years. An SO year old woman was admitted to the hospital because of mild congestive heart failure. Cardiac examination revealed a 4/6 holosystolic and a 2/6 decrescendo diastolic murmur at the left sternal border. Radiography, echocardiography, and computed tomography confirmed newly diagnosed CCTGA without associated intracardiac defects.
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A Wahl, M Billinger, M Fleisch, S de Marchi, B Meier, C Seiler (1998)  Pathophysiology of coronary collateral circulation in humans   SCHWEIZERISCHE MEDIZINISCHE WOCHENSCHRIFT 128: 41. 1527-1537 OCT 10  
Abstract: The functional relevance of coronary collaterals in humans has yet to be fully explored. Several studies demonstrated a protective role of collaterals in patients with coronary artery disease. On the other hand, negative aspects of well-developed coronary collaterals have been reported, e.g. a higher rate of restenosis following coronary angioplasty, or a redistribution of blood via collaterals away from the myocardial area in need towards normally perfused areas (coronary steal). In the past, the coronary collateral circulation has been assessed only qualitatively, using visual angiographic or nuclear imaging methods. With the recent advent of intracoronary Doppler and pressure-transducers, quantitative assessment of functional parameters of the coronary circulation has become feasible. This article reviews ongoing research in the field of coronary collaterals in humans, concerning their exact determination, the positive and negative aspects of their structure as well as their functional aspects.
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C Seiler, M Fleisch, A Garachemani, B Meier (1998)  Coronary collateral quantitation in patients with coronary artery disease using intravascular flow velocity or pressure measurements   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 32: 5. 1272-1279 NOV 1  
Abstract: Objectives. This study evaluated two methods for the quantitative measurement of collaterals using intracoronary (IC) blood flow velocity or pressure measurements. Background. The extent of myocardial necrosis after coronary artery occlusion is substantially influenced by the collateral circulation, So far, qualitative methods have been available to assess the human coronary collateral circulation, thus restraining the conclusive investigation of, for example, therapies to promote collateral development. Methods. Fifty-one patients with a coronary artery stenosis to be treated by percutaneous transluminal coronary angioplasty (PTCA) were investigated using IC PTCA guidewire-based Doppler and pressure sensors positioned distal to the stenosis, Simultaneous measurements of aortic pressure, IC velocity and pres sure distal to the stenosis during and after PTCA provided the variables for calculating collateral flow indices (CFIv and CFIp) that express collateral flow as a fraction of Row via the patent vessel, Both CFIv and CFIp were compared with conventional methods for collateral assessment, among them ST segment changes >1 mm on IC and surface electrocardiogram (ECC) at PTCA, Also, CFIv and CFIp were compared with each other. Results. In II patients without ECG signs of ischemia during PTCA (sufficient collaterals), relative collateral flow amounted to 46% as determined by Doppler and pressure wire. Patients with insufficient collaterals (n = 40) had relative collateral flow values of 18%. Using a threshold of CFI = 30%, sufficient and insufficient collaterals could be diagnosed with 100% sensitivity and 93% specificity by IC Doppler, and 75% sensitivity and 92% specificity by IC pressure measurements. The agreement between Doppler and pressure measurements was good: CFIv = 0.08 + 0.8 CFIp, r = 0.80, p = 0.0001, Conclusions. Intracoronary Row velocity or pressure measurements during routine PTCA represent an accurate and, at last, quantitative method for assessing the coronary collateral circulation in humans. (C) 1998 by the American College of Cardiology.
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M Pfister, C Seiler, M Fleisch, H Gobel, T Luscher, B Meier (1998)  Nitrate induced coronary vasodilatation : differential effects of sublingual application by capsule or spray   HEART 80: 4. 365-369 OCT  
Abstract: Background-Sublingual nitroglycerin (glyceryltrinitrate, GTN) capsules or isosorbide dinitrate (ISDN) spray are routinely used to treat anginal attacks and to vasodilate maximally the epicardial coronary arteries during coronary angiography. Objective-To compare the coronary vasodilatory effects of GTN capsules and ISDN spray with those induced by intracoronary GTN using quantitative coronary angiography. Design-96 patients (79 men and 17 women; median age 59 years) were randomised to four groups to receive either a sublingual capsule containing 0.8 mg GTN or two puffs of spray delivering 0.8 mg ISDN, followed or preceded by an intracoronary bolus of 0.2 mg GTN used as reference for maximal vasodilatation. Results-There was a significant increase in the mean diameter of coronary arteries in angiographically normal segments in patients who received either intracoronary GTN (groups 1 and 2) or ISDN spray (group 4) as a first application (group 1, 0.46 mm, +17%, (baseline vessel diameter 100%), p < 0.001; group 2, 0.45 mm, +13%, p < 0.001; group 4, 0.47 mm, +13%, p < 0.05). Patients who received a sublingual GTN capsule as the first application mode (group 3) had no significant change in epicardial vessel diameter (0.10 mm, +5%, p = 0.3). Conclusions-Sublingual ISDN spray may be more efficacious than sublingual GTN capsules in certain patients with anginal attacks. ISDN spray should be preferred over capsules in coronary angiographic procedures.
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S Senti, M Fleisch, M Billinger, B Meier, C Seiler (1998)  Long-term physical exercise and quantitatively assessed human coronary collateral circulation   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 32: 1. 49-56 JUL  
Abstract: Objectives. This prospective, cross-sectional study sought to determine an association between the level of long-term physical activity as well as other clinical and angiographic variables and an index of collateral flow to the vascular region undergoing percutaneous transluminal coronary angioplasty (PTCA). Background. There is limited and conflicting information about the effect of physical exercise on the coronary collateral circulation in humans, partly because previous studies lacked a quantitative means of assessing collateral channels. Methods. In 79 patients (mean [+/-SD] age 58 +/- 10 years),vith coronary artery disease undergoing PTCA (no transmural myo cardial infarction), a coronary collateral flow index was determined as the ratio between the intracoronary (IC) distal flow velocity time integral during (Vi(occl) [cm]) and after (Vi(phi-occl) [cm]) PTCA of the stenosis. Vi(occl)/Vi(phi-occl) was measured by a 0.014-in. Doppler guide sire, from which an IC electrocardiogram (ECG) was also recorded. Patients without ECG ST-T wave changes during PTCA were considered to have sufficient collateral channels (n = 29); those with ST-T wave changes were considered to have insufficient collateral channels (n = 50). The level of long-term physical activity was determined by a structured interview (score from 1 to 4). Univariate and multivariate analyses were used to find associations between physical activity as well as 30 other clinical and angiographic variables and the collateral flow index. Results. Long-term physical activity during leisure time, but not during work hours, and the severity of the stenosis undergoing PTCA were found to be independently and directly associated with sufficient versus insufficient collateral channels and with Vi(occl)/Vi(phi-occl) (leisure time physical activity [LTPA] score 3.3 +/- 0.9 vs. 2.4 +/- 1.0, p = 0.0002; percent diameter stenosis 88 +/- 12% vs. 80 +/- 14%, p = 0.001; Vi(occl)/Vi(phi-occl)= 0.1 + 0.1 LTPA score, p = 0.0002 for trend). Conclusions. In patients with coronary artery disease, the level of long-term physical activity during leisure time and the severity of the stenosis undergoing PTCA are directly associated with the quantitative degree of collateral flow. (C) 1998 by the American College of Cardiology.
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1997
C Seiler, U Kaufmann, B Meier (1997)  Intracoronary demonstration of adenosine-induced coronary collateral steal   HEART 77: 1. 78-81 JAN  
Abstract: A steal phenomenon was detected by intravascular Doppler guidewire in a patient with a well collateralised coronary vascular area supplied by a reopened left circumflex coronary artery, This phenomenon accounted for the fall in blood flow velocity reserve during hyperaemic conditions to 50% of the baseline value. The collaterals must have been the cause of the steal phenomenon because complete revascularisation af the lesion barely reversed it.
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U Zingg, B Aeschbacher, C Seiler, U Althaus, T Carrel (1997)  Early experience with the new masters series of St. Jude Medical heart valve : In vivo hemodynamic and clinical results in patients with narrowed aortic annulus   JOURNAL OF HEART VALVE DISEASE 6: 5. 535-541 SEP  
Abstract: Background and aims of the study: Aortic valve replacement in the small aortic root results in a heart-prosthesis mismatch in a significant number of patients. The new Masters series of St. Jude Medical (SJM) valves represents the company’s most recent innovation, combining the beneficial Hemodynamic Plus (HP) characteristics with rotatability. Thus, this valve allows for a larger valve orifice area with an equivalent tissue annulus diameter and reduces the potential interferences of subannular tissue with leaflet mobility. Methods: We compared prospectively the hemodynamic characteristics and the early clinical results in four groups of 25 patients each who received either the 21 Masters-HP, the 21 Standard, the 21 HP or the 23 Standard SJM valves. Patients were selected from our database and matched rigorously for age, gender, body surface area, NYHA functional class, underlying lesion, native valve opening area and left ventricular function, as well as preoperative peak and mean valve gradients. Postoperative evaluation included clinical examination and echocardiographic studies before hospital discharge and at six months. Results: Short-term clinical follow up was marked by a complete absence of valve-related complications in all groups. Doppler-derived mean and maximal pressure gradients were significantly lower in the 21 HP (8.7 +/- 3.1 mmHg and 15.1 +/- 4.0 mmHg, respectively) and 21 Masters-HP groups (8.9 +/- 2.6 mm +/- Hg and 14.5 +/- 3.8 mmHg) than those in the 21 Standard group (15.1 +/- 3.2 mmHg and 22.5 +/- 6.1 mmHg; p = 0.002 and p = 0.004, respectively). These results confirm that the superior hemodynamic performance of the HP series is maintained in the Masters-HP valve, despite the introduction of a new cuff design allowing rotatability. Pressure gradients did not differ significantly between the 21 HP, the 21 Masters-HP and the 23 Standard groups. Conclusions: The hemodynamic performance of the 21 Masters-HP SJM valve corresponds closely with that of the 21 HP and 23 Standard valves and is substantially better than that of the 21 Standard valve. The Masters-HP valve will continue to reduce cardiac-prosthesis mismatch in normal-sized patients with a narrowed aortic root; its performance index is equal to that of the 21 HP valve and significantly higher than that of the 21 Standard valves. The valve will also further reduce the need for aortic annulus enlargement.
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C Seiler, M Fleisch, B Meier (1997)  Direct intracoronary evidence of collateral steal in humans   CIRCULATION 96: 12. 4261-4267 DEC 16  
Abstract: Background Coronary steal is defined as a fall in blood flow toward a certain vascular region in favor of another area during arteriolar vasodilatation, ie, a coronary flow velocity reserve (CFVR) <1. The purpose of this study was to determine the frequency of steal in patients with a wide range of collateral supply to a vascular area of interest and to assess whether steal is associated with the amount of collateral flow. Methods and Results One hundred patients 57+/-9 years old with a coronary artery stenosis to be dilated were examined with intracoronary (IC) Doppler guidewires. IC adenosine-induced CFVR<1 obtained distal to the stenosis was defined as steal. An index for collateral flow was determined by positioning the Doppler guidewire in the collateral-dependent vessel distal to the stenosis and measuring the flow velocity time integral during (Vi(occl), cm) and after (Vi((sic)-occl)) balloon occlusion. Vi(occl)/Vi((sic)-occl) was determined without and with intravenous adenosine (140 mu g.kg(-1).min(-1)). Coronary steal occurred in 10 of 100 patients. Patients with steal showed superior collaterals compared with those without steal: Vi(occl)/Vi(sic)-occl) = 0.65+/-0.24 in patients with steal versus 0.29+/-0.18 in those without steal (P=.0001). In all patients with steal, there was a reduction in collateral flow during intravenous adenosine-induced hyperemia, whereas in the majority (70%) of patients without steal, collateral flow increased or remained unchanged during hyperemia. Conclusions Coronary steal assessed by intracoronary Doppler flow velocity measurements occurs in 10% of patients with a wide range of coronary collaterals to the vascular area from which blood flow is redistributed. There is a direct association between the presence of steal away from and the amount of collateral flow toward the region under investigation. Collateral flow to the vascular region studied decreases during adenosine-induced hyperemia, which indicates a mechanism of steal via the extensive collaterals.
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1996
J Frielingsdorf, P Kaufmann, C Seiler, G Vassalli, T Suter, O M Hess (1996)  Abnormal coronary vasomotion in hypertension : Role of coronary artery disease   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 28: 4. 935-941 OCT  
Abstract: Objectives. This study sought to evaluate the effect of dynamic exercise on coronary vasomotion in hypertensive patients in the presence and absence of coronary artery disease. Background. Endothelial dysfunction with abnormal coronary vasodilation in response to acetylcholine has been reported in patients with arterial hypertension. Methods. Coronary artery dimensions of a normal and stenotic vessel segment were determined in 64 patients by biplane quantitative coronary arteriography at rest and during supine bicycle exercise. Patients were classified into two groups: 20 patients without evidence of coronary artery disease (10 normotensive, 10 hypertensive [group 1]) and 44 patients,vith coronary artery disease (26 normotensive, 18 hypertensive [group 2]). Both groups were comparable with regard to clinical characteristics, serum cholesterol levels, body mass index, exercise capacity and hemodynamic data. Results. Mean aortic pressure was significantly higher in hypertensive than normotensive patients. Exercise-induced vasodilation of the normal vessel segment was similar in normotensive and hypertensive patients without coronary artery disease (group 1), namely, +19% versus +20%. However, in hypertensive patients with coronary artery disease, exercise-induced vasodilation was significantly less in both normal and stenotic vessel segments than in normotensive subjects (+1% vs. +20% for normal [p < 0.003] and -20% vs. -5% for stenotic vessels [p < 0.025]), Administration of 1.6 mg of sublingual nitroglycerin at the end of exercise led to a normalization of the vasodilator response in normotensive as well as hypertensive patients. However, this response became progressively abnormal in group 2 when coronary artery disease was present. Conclusions. In the absence of coronary artery disease, the vasomotor response to exercise is normal in both normotensive and hypertensive patients. However, in hypertensive patients with coronary artery disease, an abnormal response of the coronary vessels can be observed, with a reduced vasodilator response to exercise in normal arteries but an enhanced vasoconstrictor response in stenotic arteries. This behavior of the epicardial vessels during exercise suggests the occurrence of endothelial dysfunction (i.e., functional defect) that is not evident in the absence of coronary artery disease. Nitroglycerin reverses impaired coronary vasodilation, but this effect is blunted in the presence of coronary artery disease (i.e., structural defect).
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C Seiler, R Jenni (1996)  Severe aortic stenosis without left ventricular hypertrophy : Prevalence, predictors, and shortterm follow up after aortic valve replacement   HEART 76: 3. 250-255 SEP  
Abstract: Objectives - The purpose of the present study in patients with severe aortic stenosis was to assess the prevalence of absent left ventricular hypertrophy (LVH) (determined according to mass criteria), to identify predictors of absent LVH, and to assess short-term left ventricular adaptation and prognosis after aortic valve replacement. Methods - Left ventricular mass (LVM) was determined by echocardiography in 109 men and 101 women with severe aortic stenosis (mean pressure gradient less than or equal to 50 mm Hg). LVH was defined as LVM greater than or equal to 109 g/m(2) in women and LVM greater than or equal to 134 g/m(2) in men. Results - One hundred and eighty nine patients showed LVH (group 1) (90%; mean (SD) age 65 (14) years), and 21 showed no LVH (group 2) (10%, age 57 (21) years P = 0.02 for difference in age). Twelve (6%) of those without LVH had increased relative wall thickness (that is, greater than or equal to 0.45 with LV concentric remodelling) and nine (4%) showed no macroscopically detectable hypertrophic adaptation. The following variables were associated with the absence of LVH: low body surface area, low body mass index, and increased cardiac index. 76/210 patients were followed up a mean of six months after aortic valve replacement. The frequency of adequate ventricular adaptation to the decreased afterload after aortic valve replacement was higher in patients with LVH than in those without. Mortality six months after aortic valve repacement was lower, but not significantly, in patients with LVH (7.6%) than in those without LVH (12.5%, P = 0.10). Conclusions - A tenth of patients with severe aortic stenosis did not develop LVH according to mass criteria; 4% of the patients did not have any macroscopic signs of myocardial adaptation to the pressure overload despite longstanding disease. Small body size was independently associated with lack of LVH according to mass criteria. Six months after aortic valve replacement, ventricular adaptation was more often adequate in patients with LVH than in those without.
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C Seiler, B Meier (1996)  Risks involved in invasive cardiologic diagnostic or therapeutic interventions   SCHWEIZERISCHE MEDIZINISCHE WOCHENSCHRIFT 126: 14. 559-565 APR 6  
Abstract: The risk of invasive cardiologic interventions being associated with morbid and mortal events is substantially related to the absolute numbers in whom these procedures are performed and this, in turn, is due to the epidemiologic significance of diseases of the cardiovascular system in industrialized countries. Diagnostic cardiac catheterization with coronary angiography is an invasive procedure with a relatively low risk of complications (approximate to 1%) or death (approximate to 0.1%). Percutaneous transluminal coronary angioplasty (PTCA), on the other hand, carries a risk of complications of approximate to 4% and has a mortality of approximate to 1%. The major source of complications with intracoronary stent implantations relates to their thrombogenicity with acute or subacute closure of the vessel (rate of complications 6-15%, mortality approximate to 2%). In vessels of less than or equal to 3 mm in diameter, the restenosis rate of a stenotic lesion treated with a stent approximates that of conventional PTCA (one third). Patients with reduced left ventricular ejection fraction are at substantial risk if treated with drugs instead of bypass surgery (better long-term survival in the latter group).
Notes: 99th Continuing Education Conference of the Schweizerischen-Gesellschaft-fur-Innere-Medizin, BERN, SWITZERLAND, OCT 19-21, 1995
J Frielingsdorf, C Seiler, P Kaufmann, G Vassalli, T Suter, O M Hess (1996)  Normalization of abnormal coronary vasomotion by calcium antagonists in patients with hypertension   CIRCULATION 93: 7. 1380-1387 APR 1  
Abstract: Background Endothelial dysfunction with a loss of endothelium-dependent vasodilation has, been reported in patients with arterial hypertension. The purpose of the present study was to evaluate coronary vasomotor response to dynamic exercise in patients with coronary artery disease with and without arterial hypertension and to determine the effect of calcium antagonists on coronary vasomotion. Methods and Results Cross-sectional areas of a normal and a stenotic coronary vessel segment were examined in 79 patients with coronary artery disease at rest and during supine bicycle exercise administration of a calcium antagonist (diltiazem or nicardipine), during exercise, and after sublingual nitroglycerin (percent change compared with rest=100%) was assessed by biplane quantitative coronary arteriography. Patients were divided into two groups: Group 1 (control) consisted of 48 patients without (normotensive subjects, n=30; hypertensive subjects, n=18) and group 2 of 31 patients with (normotensive subjects, n=15; hypertensive subjects, n=16) pretreatment with a calcium antagonist immediately before exercise. The groups did not differ with regard to clinical characteristics or hemodynamic data measured during exercise. Mean aortic pressure at rest, however, was significantly increased in hypertensive patients compared with normotensive subjects in group 1 (103 mm Hg versus 92 mm Hg, P<.01) and group 2 (110 mm Hg versus 98 mm Hg, P<.025). In group 1, exercise-induced vasomotor response was significantly different between normotensive and hypertensive patients in normal (+20% versus +1%. P<.003) and stenotic vessels (-5% versus -20%, P<.025). However, in group 2 there was coronary vasodilation in normotensive and hypertensive patients for both normal (Delta Ex +23% versus +21%, P=NS) and stenotic vessel segments (+24% versus +26%, P=NS). Conclusions Abnormal coronary vasomotion during exercise can be observed in hypertensive patients with reduced vasodilator response in normal arteries and enhanced vasoconstrictor response in stenotic arteries. Calcium antagonists prevent the abnormal response of normal and stenotic coronary arteries to exercise in hypertensive patients and thus may compensate for endothelial dysfunction with reduced vasodilator response to exercise.
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1995
C SEILER, M RITTER, V WIDMER, R JENNI (1995)  PREVALENCE OF ABSENT LEFT-VENTRICULAR HYPERTROPHY (LVH) IN SEVERE, PREDOMINANT AORTIC-STENOSIS - INFLUENCE OF LVH DEFINITION   SCHWEIZERISCHE MEDIZINISCHE WOCHENSCHRIFT 125: 11. 521-530 MAR 18  
Abstract: 210 out of approximately 16,000 Doppler echocardiographic examinations between 1989 and 1992 at the University Hospital of Zurich, Switzerland, produced the diagnosis of severe, longstanding and predominant aortic stenosis with a mean transvalvular pressure gradient of greater than or equal to 50 mm Hg. These patients, who had no significant valvular heart disease other than aortic stenosis and no coronary artery disease, were investigated for the prevalence and for existing gender predominance of absent left ventricular hypertrophy (LVH) using eight different, clinically established and validated definitions for LVH. 4 to 44% of all study patients were found to have absent LVH depending on how LVH was defined. There was no gender predominance in patients without LVH ii a gender-specific LVH definition was used. Defining absent LVH as LV mass index <109 g/m(2) body surface area (for women) and <134 g/m(2) body surface area (for men) combined with relative LV wall thickness <0.45, the prevalence of absent LVH amounted to 4% (9/210 patients). The majority of patients had concentric LVH (132/210), 57/210 patients had excentric LVH, and 12/210 had concetric LV remodeling. There was a significant inverse association between the time elapsed since diagnosis of aortic stenosis and the finding of absent LVH. However, average duration since diagnosis of aortic stenosis in patients without LVH was quite long averaging 3.2 years. Therefore, factors other than duration of the disease and not investigated in this study seem to be more closely related to the absence of LVH.
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C SEILER (1995)  HYPERTROPHIC CARDIOMYOPATHY - SPONTANEOUS COURSE   SCHWEIZERISCHE MEDIZINISCHE WOCHENSCHRIFT 125: 41. 1931-1939 OCT 14  
Abstract: Hypertrophic cardiomyopathy is a relatively rare (prevalence approximate to 0.2%), primary myocardial disorder with an autosomal pattern of inheritance, characterized by mostly asymmetric left ventricular hypertrophy with myocyte and myofibrillar disarray. To date, about 34 mutations of the beta-cardiac myosin heavy chain gene have been described and shown to have prognostic implications. The disease has an annual mortality rate of 3%, related to both sudden cardiac death and progressive systolic dysfunction. Not only diastolic but also progressive systolic dysfunction with cavity dilatation occurs in a minority of patients with severe hypertrophy during the long-term course. Sudden death often occurs in young, asymptomatic or mildly symptomatic patients. The degree of hypertrophy and the presence of a pressure gradient are of little prognostic significance. Nonsustained ventricular tachycardia is associated with a poor prognosis in the presence of a history of syncope.
Notes: Annual Joint Meeting of the Societe-Suisse-de-Cardiologie/Societe-Suisse-de-Chirurgie-Thoracique-et- Cardiovasculaire/Societe-Suisse-d-Angiologie/Societe-Suisse-de-Chirurgie -Vasculaire, LUGANO, SWITZERLAND, APR 06-08, 1995
C SEILER, R JENNI, G VASSALLI, M TURINA, O M HESS (1995)  LEFT-VENTRICULAR CHAMBER DILATATION IN HYPERTROPHIC CARDIOMYOPATHY - RELATED VARIABLES AND PROGNOSIS IN PATIENTS WITH MEDICAL AND SURGICAL THERAPY   BRITISH HEART JOURNAL 74: 5. 508-516 NOV  
Abstract: Background-To determine the incidence and prognosis of left ventricular dilatation and systolic dysfunction in 139 patients with hypertrophic cardiomyopathy during long term follow up, Methods-Left ventricular chamber dilatation and systolic dysfunction (both together referred to as left ventricular chamber dilatation) were determined echocardiographically. Chamber dilatation was defined as an increase in the left ventricular end diastolic diameter of >2% per year combined with a decrease in midventricular systolic fractional shortening of >2% per year of follow up [10.3 (SD 6) years]. The predictive value for left ventricular chamber dilatation of clinical, invasive, and echocardiographic variables and its prognosis were assessed. Results-In 119 of 139 individuals (86%), left ventricular chamber size and systolic function remained stable (group 1), and in 20/139 patients (14%) left ventricular chamber dilatation occurred during follow up (group 2). At baseline examination, symptoms such as dyspnoea and syncope occurred less often in group 1 than in group 2; New York Heart Association classification was lower in group 1 than in group 2 (P = 0.001). Left ventricular mass index relative to sex specific normal values was increased by 18% in group 1 and by 41% in group 2 (P = 0.04). Cumulative survival rates were slightly although not significantly higher in group 1 than in group 2. Event-free survival was significantly higher in group 1 than in group 2 (P < 0.05). Conclusions-(1) The development of left ventricular chamber dilatation and systolic dysfunction in hypertrophic cardiomyopathy occurs in approximately 1.5% of the patients per year. (2) Factors associated with left ventricular dilatation are dyspnoea, syncope, a higher functional classification, and a higher degree of left ventricular hypertrophy. (3) Patients with chamber dilatation have a worse prognosis than those without, particularly regarding quality of life.
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C Seiler, M Ritter, V Widmer, R Jenni (1995)  Severe aortic stenosis without left ventricular hypertrophy : Associated variables and prognosis after aortic valve replacement   SCHWEIZERISCHE MEDIZINISCHE WOCHENSCHRIFT 125: 51-52. 2502-2505 DEC 26  
Abstract: The purpose of the present study in patients with severe aortic stenosis was to assess prevalence, predictors and course after aortic valve replacement in patients without left ventricular hypertrophy according to echocardiographic mass criteria (LVH). 90% had LVH compared with 10% without. The following variables were associated with absence of LVH: younger age, low body surface area, and increased cardiac index. In patients with LVH, ventricular adaptation following aortic valve replacement was adequate more often than in those without. Six-month mortality following aortic valve replacement was insignificantly lower in patients with LVH (7.6%) than in those whithout it (12.5%, p = 0.10).
Notes: 63rd Annual Assembly of the Societe-Suisse-de-Medecine-Interne, MONTREUX, SWITZERLAND, MAY 18-20, 1995
C SEILER, T M SUTER, O M HESS (1995)  EXERCISE-INDUCED VASOMOTION OF ANGIOGRAPHICALLY NORMAL AND STENOTIC CORONARY-ARTERIES IMPROVES AFTER CHOLESTEROL-LOWERING DRUG-THERAPY WITH BEZAFIBRATE   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 26: 7. 1615-1622 DEC  
Abstract: Objectives. We attempted to determine whether the coronary vasomotor response to exercise improves after cholesterol-lowering drug therapy with bezafibrate. Background. Hypercholesterolemia and other coronary risk factors are associated with impaired endothelium dependent coronary vasomotor response to physiologic or pharmacologic stimuli, even in the absence of overt coronary atherosclerosis. It is still unknown whether the coronary artery vasomotor response to dynamic exercise improves under cholesterol-lowering drug therapy. Methods. Of 15 male patients (age 51 +/- 7 years [mean +/- SD]) included in the study, 7 had markedly elevated cholesterol levels (greater than or equal to 6.5 mmol/liter, therapy group), and 8 had normal or slightly elevated cholesterol levels (<6.5 mmol/liter, control group). At baseline and after 7 months of cholesterol-lowering therapy with bezafibrate (400 mg/day) in the therapy group, coronary vasomotor response to dynamic exercise (percent change in cross-sectional vascular area at maximal exercise vs, rest [100%]) in normal and stenotic, previously dilated vessels was assessed by quantitative coronary angiography. Results. During follow up, total serum cholesterol levels in the therapy group decreased from 7.8 +/- 1.1 to 5.8 +/- 1.1 mmol/liter (p = 0.0001) and did not change significantly in the control group (from 5.4 +/- 0.9 to 6.0 +/- 1.2 mmol/liter, p = NS). Exercise-induced vasomotor response (at similar work loads in the therapy and control groups) in both normal and dilated stenotic coronary arteries improved significantly in the therapy group, from 100 +/- 9% to 109 +/- 7% (p = 0.0001, cross-sectional area at rest 100%) and from 80 +/- 11% to 106 +/- 7% (p = 0.0002), respectively, but did not improve during follow up in the control group. Conclusions. The present study indicates that cholesterol lowering drug therapy with bezafibrate for 7 months improves exercise-induced vasomotion of angiographically normal coronary arteries. Seven months after coronary angioplasty, the reduction in serum cholesterol levels is, at least in part, associated with a restoration of the initially disturbed vasomotor response of stenotic vessel segments to exercise. (J Am Coll Cardiol 1995;26:1615-22)
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1994
G VASSALLI, C SEILER, O M HESS (1994)  RISK STRATIFICATION IN HYPERTROPHIC CARDIOMYOPATHY   CURRENT OPINION IN CARDIOLOGY 9: 3. 330-336 MAY  
Abstract: Hypertrophic cardiomyopathy is a primary myocardial disorder with an autosomal pattern of inheritance, characterized by asymmetric left ventricular hypertrophy with myocyte and myofibrillar disarray. Approximately 30% to 50% of all cases are accounted for by mutations in the beta-cardiac myosin heavy chain gene on chromosome 14q1. Recent linkage analysis led to the association of the disease with additional loci on chromosomes 1q3, 11p13-q13, and 15q2, but the underlying gene defects are as yet unidentified. To date, about 34 mutations of the beta-cardiac myosin heavy chain gene have been described and shown to have important prognostic implications. Definite genotype-phenotype correlations have been described; however, wide diversity in cardiac morphology, pathophysiologic features, and clinical manifestations is still evident, even within the same family. The disease has an annual mortality of approximately 3%, related to both progressive heart failure and sudden cardiac death. Not only diastolic but also progressive systolic dysfunction with cavity dilatation occurs in a minority of patients with severe left ventricular hypertrophy. These patients usually have a poor prognosis, especially when atrial fibrillation ensues. Sudden death often occurs in young, asymptomatic or mildly symptomatic patients. The degree of hypertrophy and the presence of a pressure gradient are of little prognostic significance. Nonsustained ventricular tachycardia is associated with a poor prognosis in the presence of a history of syncope.
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1993
C SEILER, R L KIRKEEIDE, K L GOULD (1993)  MEASUREMENT FROM ARTERIOGRAMS OF REGIONAL MYOCARDIAL BED SIZE DISTAL TO ANY POINT IN THE CORONARY VASCULAR TREE FOR ASSESSING ANATOMIC AREA AT RISK   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 21: 3. 783-797 MAR 1  
Abstract: Objectives. To obtain the size of regional myocardial mass for individual coronary arteries in vivo. Background. The anatomic site of occlusion in a coronary artery does not predict the size of the risk area because location of the occlusion does not account for the size of the artery or of its dependent myocardial bed. Methods. Intracoronary radiolabeled microspheres were injected and coronary arteriograms were quantitatively analyzed by semiautomated methods. The coronary artery lumen areas and the sum of epicardial coronary artery branch lengths distal to the points where radiomicrospheres had been injected were determined from both in vivo and postmortem coronary arteriograms. Regional myocardial mass distal to the point of each microsphere injection was correlated with corresponding distal summed coronary branch lengths and with coronary artery lumen areas. Results. 1) Regional myocardial mass was closely and linearly related to sum of coronary artery branch lengths distal to any point in the coronary artery tree and therefore could be determined for any location on a coronary arteriogram. 2) The fraction of total left ventricular mass at risk distal to a stenosis could be determined from the corresponding fraction of total coronary artery tree length independently of the scale or X-ray magnification used to measure absolute branch lengths. 3) Cross-sectional lumen area at any point in the left coronary artery tree was closely related to the size of the dependent vascular bed with a curvilinear relation similar to that observed in humans with normal coronary arteriograms. Conclusions. On coronary arteriograms, the anatomic area at risk for myocardial infarction distal to any point in the coronary artery tree can be determined from the sum of distal coronary artery branch lengths. There is a curvilinear relation between coronary artery lumen area and dependent regional myocardial mass comparable to that in humans, reflecting fundamental physical principles underlying the structure of the coronary vascular tree.
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C SEILER, O M HESS, M BUECHI, T M SUTER, H P KRAYENBUEHL (1993)  INFLUENCE OF SERUM-CHOLESTEROL AND OTHER CORONARY RISK-FACTORS ON VASOMOTION OF ANGIOGRAPHICALLY NORMAL CORONARY-ARTERIES   CIRCULATION 88: 5, Part 1. 2139-2148 NOV  
Abstract: Background. It has been shown that there is impairment of the vasodilatory response to acetylcholine in patients with hypercholesterolemia and angiographically normal coronary arteries. Moreover, in patients with angiographically smooth coronary arteries, the number of coronary risk factors is associated with a loss of endothelium-dependent vasodilation. The purpose of the present analysis was to evaluate in patients with and without coronary artery disease coronary vasomotor response to dynamic exercise in angiographically normal and stenosed coronary arteries and to relate the response to serum cholesterol levels as well as to other coronary risk factors. Methods and Results. Luminal area change during exercise (delta-ex, percent change compared with rest=100%) was determined by biplane quantitative coronary arteriography in three groups: Group 1 consisted of 14 patients with normal total serum cholesterol of <200 mg/100 mL; mean, 173 mg/100 mL (mean age, 51 years). Group 2 comprised 23 patients with a slightly elevated cholesterol of 200 to 250 mg/100 mL; mean, 223 mg/100 mL (mean age, 53 years). Group 3 had 24 patients with markedly elevated cholesterol of >250 mg/100 mL; mean, 288 mg/100 mL (mean age, 54 years). Serum cholesterol levels and categorical risk factors such as positive family history, history of hypertension, smoking, obesity, and diabetes were related to exercise-induced vasomotor response. The three groups did not differ with regard to clinical characteristics, exercise work load, and hemodynamic data measured during exercise. However, delta-ex in normal vessels was significantly different between all three groups (ANOVA, P<.01): +31% (group 1), +18% (group 2), and +4% (group 3). Delta-ex in stenotic vessels did not differ between the groups: -5% (group 1), -13% (group 2), and -12% (group 3). Delta-ex of the nonstenosed vessel correlated significantly and inversely with total cholesterol, with low-density lipoprotein cholesterol, with the ratio of total to high-density lipoprotein cholesterol, and with the number of coronary risk factors present in a patient. High total cholesterol and a history of hypertension were independent risk factors for impaired coronary vasomotion. Conclusions. In patients with and without coronary artery disease, hypercholesterolemia and a history of hypertension independently impair exercise-induced coronary vasodilation in angiographically normal coronary arteries. In the stenotic vessel, vasomotion during exercise does not appear to be influenced by the actual serum cholesterol. The precise mechanism by which the impaired vasomotion of the angiographically normal coronary arteries is mediated is unknown, but a direct negative effect of hypercholesterolemia on endothelial function or early undetected atherosclerosis appears to be the most likely explanation.
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1992
C SEILER, R L KIRKEEIDE, L GOULD (1992)  BASIC STRUCTURE-FUNCTION RELATIONS OF THE EPICARDIAL CORONARY VASCULAR TREE - BASIS OF QUANTITATIVE CORONARY ARTERIOGRAPHY FOR DIFFUSE CORONARY-ARTERY DISEASE   CIRCULATION 85: 6. 1987-2003 JUN  
Abstract: Background. Quantitative coronary arteriography has been validated for stenotic segments of coronary arteries. However, it does not currently account for diffuse coronary artery disease, because the normal size of the coronary artery for its distal myocardial bed size is not known and cannot be measured directly with diffuse involvement of the artery. Methods and Results. From clinical coronary arteriograms of 12 patients without coronary artery disease (group 1) and in 17 patients with coronary artery disease (group 2), we determined by quantitative coronary arteriography 1) the relations among measured coronary artery cross-sectional lumen area, summed distal branch lengths, and regional myocardial mass distal to each point in each coronary artery; 2) the ratio of coronary artery lumen area between parent and daughter vessels at 50 bifurcations; and 3) which of three different theoretical physical principles could underlie the tree structure of the human coronary artery system, by comparing the coronary artery size, branch lengths, regional mass, and relations between parent-to-daughter lumen area ratios with those for the different theoretical physical principles to test which principle best fit the observed data and therefore which principle most probably characterizes the human coronary artery tree structure. The results showed that 1) there is a close correlation between the lumen area of a coronary artery at each point along its length and the corresponding summed distal branch lengths and regional myocardial mass in patients without and with coronary artery disease; 2) measured coronary artery lumen area in patients with coronary artery disease is diffusely 30-50% too small for distal myocardial bed size compared with normal subjects; and 3) the observed relations among coronary artery size, distal summed lengths, myocardial bed size, and parent-to-daughter size ratios are not consistent with the theoretical principle of constant mean blood flow velocity in the coronary circulation but are consistent with the principles of minimum viscous energy loss and of limited/adaptive vascular wall shear stress characterized by a 2/3 power law relating coronary artery lumen area to distal summed branch lengths and regional mass or parent-to-daughter branching ratios. Conclusions. These observations provide a basis for quantifying diffuse coronary artery disease on clinical arteriograms.
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C SEILER, A LASKE, A GALLINO, M TURINA, R JENNI (1992)  ECHOCARDIOGRAPHIC EVALUATION OF LEFT-VENTRICULAR WALL MOTION BEFORE AND AFTER HEART-TRANSPLANTATION   JOURNAL OF HEART AND LUNG TRANSPLANTATION 11: 5. 867-874 SEP  
Abstract: Forty transplanted hearts were retrospectively investigated before, immediately after, and 15 +/- 12 months after heart transplantation by two-dimensional echocardiography for the presence and course of left ventricular myocardial wall motion abnormalities. Fourteen heart donors who were brain dead because of subarachnoid hemorrhage formed group 1 (mean age, 35 years); 21 heart donors who were brain dead because of head injury formed group 2 (mean age, 29 years), and five heart donors who were brain dead because of head injury with an additional chest trauma formed group 3 (mean age, 28 years). Myocardial wall motion was examined in six different myocardial segments (inferior, septal, anterior, posterior, posterolateral, apical) and was quantitatively assessed by a modified score index system (score index 0 = normal wall motion; score index 1 = diffuse hypokinesia). Overall, 27 of the 40 heart donors showed mild to severe (9 of the 40) wall motion abnormalities, which improved shortly after heart transplantation (score index: 0.36 vs 0.18, p < 0.01), and remained improved 15 months after heart transplantation (score index: 0.15). Among the different study groups, a significant improvement occurred in the myocardial wall motion score index on a short-term and long-term basis in all the groups, except for group 2, regarding the long-term follow-up. This study concluded that brain-dead, potential heart donors often reveal mild-to-severe left ventricular wall motion abnormalities, which are readily detected and semiquantitated by two-dimensional echocardiography. Such patients need not be excluded as heart donors if no heart disease or cardiovascular risk factors can be found in their histories or if a normal coronary angiogram is obtained in patients with cardiovascular risk factors; heart donors recruited on the basis of these criteria most often show a restitution of myocardial dysfunction after transplantation.
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1991
C SEILER, O M HESS, M SCHOENBECK, J TURINA, R JENNI, M TURINA, H P KRAYENBUEHL (1991)  LONG-TERM FOLLOW-UP OF MEDICAL VERSUS SURGICAL THERAPY FOR HYPERTROPHIC CARDIOMYOPATHY - A RETROSPECTIVE STUDY   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 17: 3. 634-642 MAR 1  
Abstract: In a retrospective analysis 139 patients with hypertrophic cardiomyopathy were followed up for 8.9 years (range 1 to 28 years). Patients were divided into two groups: Group 1 consisted of 60 patients with medical therapy and Group 2 of 79 patients with surgical therapy (septal myectomy). Groups 1 and 2 were subdivided according to the medical treatment. Group 1a received propranolol, 160 mg/day (n = 20); Group 1b verapamil, 360 mg/day (n = 18); and Group 1c, no therapy (n = 22). Group 2a received verapamil, 120 to 360 mg/day, after septal myectomy (n = 17) and Group 2b had no medical therapy after surgery (n = 62). In Group 1, 19 patients died (annual mortality rate 3.6%) and in Group 2, 17 patients died (mortality rate 2.4%, p = NS). Of the patients who died, approximately one half to two thirds in both Groups 1 and 2 died suddenly and the other one half to one third died because of congestive heart failure. The 10 year cumulative survival rate was 67% in Group 1, significantly smaller than that in Group 2 (84%, p < 0.05). In the subgroups, the 10 year survival rate was 67% in Group 1a, 80% in 1b (p < 0.05 versus 1a) and 65% in 1c (p < 0.05 versus 1b). The 10 year survival rate was 100% in Group 2a (p < 0.05 versus 1a, 1b, 1c) and 78% in Group 2b (p < 0.05 versus 2a). It is concluded that cumulative survival rate is significantly better in surgically than in medically treated patients. However, the survival rate among medically treated patients was better in those treated with verapamil than in those treated with propranolol or in untreated patients. The 10 year survival rate was similar in the medically treated patients receiving verapamil (80%) and the entire surgically treated group (84%, p = NS). The most favorable outcome was observed in surgically treated patients receiving long-term therapy with verapamil, probably as a result of the reduction of systolic pressure overload by septal myectomy and improvement in left ventricular diastolic function mediated by verapamil.
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1989
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