born / geboren am 7.3. 1957 in Hessigheim am Neckar
Examinations / Abschlüsse / Anerkennungen 1976 High School Degree / Erwerb der Hochschulreife 1980 Examination as a male nurse / Krankenpflegeexamen 1986 Foreign Medical Graduate Examination in the Medical Sciences (FMGEMS) 1987 Medical Examination / Ärztliche Prüfung 1987 Approval Medical Doctor / Approbation als Arzt 1989 Dissertation / Promotion ("Regulation of LDL receptor activity in freshly isolated human mononuclear leukocytes / Regulation der Low-Density-Lipoprotein- Rezeptor-Aktivität in frisch isolierten menschlichen monokukleären Leukozyten") 1993 Board certification Internal Medicine / Anerkennung als Arzt für Innere Medizin 1998 Board certification cardiology / Schwerpunktsbezeichnung Kardiologie 1999 Board certification emergency medicine / Bereichsbezeichnung Rettungsmedizin 2000 Board certification sports medicine / Bereichsbezeichnung Sportmedizin 2000 Personal authorization to treat heart failure and heart transplant patients in Hamburg / Persönliche Ermächtigung der KV Hamburg zur Betreuung von herzinsuffizienten und herztransplantierten Patienten 2002 Supervison authorization internal medicine for 1 year / Weiterbildungsberechtigung Innere Medizin 1 Jahr, Kardiologie 1 Jahr 2003 Habilitation / Habilitation und Venia legendi für Innere Medizin ("Results of clinical studies in the border zone of cardiology and heart surgery / Ergebnisse klinischer Untersuchungen im Grenzbereich von Kardiologie und Kardiochirurgie bei terminal koronarkranken, herzinsuffizienten und herztransplantierten Patienten") 2004 Personal authorization to treat heart failure and heart transplant patients Schleswig-Holstein / Persönliche Ermächtigung der KV Schleswig-Holstein zur Betreuung von herzinsuffizienten und herztransplantierten Patienten und für Herz-Schrittmacher- und Defibrillatorkontrollen 2008 Educational certificate medical board Schleswig-Holstein / Fortbildungszertifikat der Ärztekammer Schleswig-Holstein 2009 Board certification cardiovascular preventive medicine / Kardiovaskulärer Präventivmediziner DGPR 2010 Professorship University Hamburg / außerplanmäßige Professur nach §17 Universität Hamburg
Non medical work / Nichtärztliche Tätigkeit (Krankenpflege) 1976-1977 Civil Service / Zivildienst, Krankenhaus Bietigheim 1977-1980 Male nurse education / dreijährige Ausbildung als Krankenpfleger Krankenhaus Bietigheim-Bissingen 1980-81 Male nurse / Berufstätigkeit als Krankenpfleger (Krankenhaus Bietigheim-Bissingen und Klinik am Eichert, Göppingen)
Study / Studium 1981-1987 Medizinstudium Universität Hamburg
Medical Work / Tätigkeiten als Arzt 1987-1992 University Clinic Hamburg General Medicine / Wissenschaftlicher Assistent der Medizinischen Kernklinik des Universitätsklinikums Hamburg-Eppendorf (UKE) (H Greten) 1992-2002 University Clinic Hamburg Heart Surgery Failure Unit / Wissenschaftlicher Assistent der Herz- Thorax- und Gefäßchirurgie des UKE (W. Rödiger, P. Kalmar, F. Dapper, H. Reichenspurner) 2002-2003 University Clinic Hamburg Consultant Heart Failure / Oberarzt des Universitären Herzzentrums: Bereiche Herzinsuffizienz, Herztransplantation, Schrittmacher- und Defibrillatortherapie (H. Reichenspurner, T. Meinertz) 2004 Consultant Cardiology & Heart Failure Unit / Oberarzt Medizinische Klinik am Krankenhaus Reinbek, St. Adolf-Stift (S. Jäckle) seit 2005 Leading Consultant Cardiology & Heart Failure Unit / Leitender Oberarzt Medizinische Klinik am Krankenhaus Reinbek, St. Adolf-Stift (S. Jäckle)
Visiting Physician / Hospitationen 1998 Hospitation am Sahlgrenska Hospital Göteborg (C. Kennergren) 2001 Hospitation am Columbia Presbyterian Medical Center New York (M. Deng, M. Packer)
Clinical & scientific fields of attention / Klinische & Wissenschaftliche Schwerpunkte - End stage heart failure / Terminale Herzinsuffizienz - Physical training in chronic cardiovascular diseases / Trainingsbehandlung bei chronischen Herzkrankheiten - Cardiovascular Rehab / Phase III Rehabilitation - Cardiac Resynchronization Therapy / Kardiale Resynchronisationstherapie (CRT) - Implantable Cardiovarter Defibrillator Therapy / Defibrillatortherapie - Cardiac Contractility Modulation / Kardiale Kontraktilitätsmodulation (CCM) - Pace Maker Therapy / Herzschrittmachertherapie - Pace Maker Lead Extraktion / Schrittmacherelektrodenextraktion - Heart Transplantation Care / Betreuung Herztransplantierter - Spinal Cord Stimulation in refractory angina pectoris / Neurostimulation bei schwerer koronarer Herzkrankheit - X-Ray supervision / Strahlenschutzbeauftragter - Coordination of the education of medical students in St. Adolf-Stift / Koordinator für die PJ-Ausbildung am St. Adolfstift
Scientific Highlights / Wissenschaftliche "Highlights" 1997 First description of negative effects of TMLR / Erstbeschreibung negativer Effekte der transmyokardialen Laserrevaskularisation (TMLR) 1998 First description of CA125 as marker in heart failure / Erstbeschreibung der Eignung von CA125 als Herzinsuffizienzmarker 1999 First description of interaction between cyclosporin and orlistat / Erstbeschreibung der Interaktion von Cyclosporin und Orlistat 2007 First description of hanta virus myocarditis / Erstbeschreibung einer durch Hantaviren ausgelösten Myokarditis
Clinical highlights / Klinische "Highlights" 1992: Article in "DIE ZEIT" on crisis in heart transplantation / Ein ZEIT-Artikel von Harald Bräutigam löst eine bundesweite Diskussion über den Nutzen der Herztransplantation aus 09.05.1996: Study AV delay optimization in heart failure / Erste Implantation eines DDD-Schrittmachers zur Optimierung des AV-Delay als additive Herzinsuffizienzbehandlung im Rahmen der APIC-Studie 1998: First implantation of coronary sinus leads / Erste Implantationsversuche einer Koronarsinuselektrode (Biotronik COROX) 13.09.1999: First extraction of a left ventricular lead via laser / Erstmalige Extraktion einer infizierten Schrittmacherelektrode mit Lasersystem in Norddeutschland (LLD, Spectranetics) 1999: Training program for terminal heart patients / Gründung einer Muskel-Trainingsgruppe für terminal herzinsuffiziente Patienten (Inzwischen 3 Gruppen in Hamburg unter Trägerschaft von HerzInForm) 1999: First implantation EASYTRAK coronary sinus lead / Erstmalige Implantation einer Koronarsinuselektrode in „over the wire“ Technik in Norddeutschland (Guidant EASYTRAK) 25.11.2005: First implantation of a CRT pacer using PEA sensoring / Weltweit erstmalige klinische Implantation eines biventrikulären Schrittmachers mit PEA-Sensor zur hämodynamischen Optimierung im Rahmen der CLEAR-Multicenterstudie (Sorin NewLivingSystem) 21.06.2006: First implantation of active fixation coronary sinus lead (STARFIX)/ Weltweit erstmalige klinische Implantation einer aktiv fixierbaren Koronarsinuselektrode (Medtronic STARFIX 4195) 29.08.2007: First implantation of a CCM stimulator / Erstmalige Implantation eines CCM-Stimulators in Norddeutschland (Impulse Dynamics OPTIMIZER III) 30.11.2010: First implantation of a phrenic nerve stimulator in central sleep apnea due to heart failure / Erste Implantation eines Zwerchfellstimulationssystems in Deutschland (Cardiac Concepts, RespiCardia) zur Behandlung der zentralen Schlafapnoe bei Herzinsuffizienz 28.02.2011: First implantation of a CRT defibrillator using PEA sensoring / Erste deutsche Implantation eines biventrikulären Defibrillators mit Vorhof-PEA-Sensor zur hämodynamischen Optimierung im Rahmen der SonR-Multicenterstudie (Sorin Paradym SonR) 03.11.2011: First implantation of a SVC phrenic nerve stimulator / Erstimplantation in Deutschland einer neuartigen Zwerchfellstimulatonselektrode im Rahmen der RespiCardia Studie (CardiacConcepts) 22.11.2011: First implantation of a MRT-CRT defibrillator / Erstimplantation (Deutschland Nr.2) eines neuen MRT tauglichen Defibrillators im Rahmen der Lumax 740 Masterstudie (Biotronik)
Memberships / Mitgliedschaften - Landesarbeitsgemeinschaft für Prävention und Rehabilitation Hamburg (HerzInForm) - 1. Vorsitzender - Bund Deutscher Internisten (BDI) - Deutsche Gesellschaft für Kardiologie - Herz- und Kreislaufforschung - European Society of Cardiology, Working Group on Heart Failure - European Heart Rhythm Association (EHRA) - International Society of Heart and Lung Transplantation (ISHLT) - Heart Failure Society of America Inc. - Hamburger Sportärztebund e.V. - Deutsche Gesellschaft für Prävention & Rehabilitation (DGPR) - Deutsche Herzstiftung
Reviewer / Reviewtätigkeit - Europace - PACE - Journal of Applied Physiology
Abstract: Hypertrophic cardiomyopathy (HCM) is a frequent genetic cardiac disease and the most common cause of sudden cardiac death in young individuals. Most of the currently known HCM disease genes encode sarcomeric proteins. Previous studies have shown an association between CSRP3 missense mutations and either dilated or hypertrophic cardiomyopathy, but all these studies were unable to provide comprehensive genetic evidence for a causative role of CSRP3 mutations. We used linkage analysis and identified a CSRP3 missense mutation in a large German family affected by HCM. We confirmed CSRP3 as an HCM disease gene. Furthermore, CSRP3 missense mutations segregating with HCM were identified in four other families. We used a newly designed monoclonal antibody to show that Muscle LIM protein (MLP), the protein encoded by CSRP3, is a mainly cytosolic component of cardiomyocytes and not tightly anchored to sarcomeric structures. Our functional data from both in vitro and in vivo analyses suggest that at least one of MLP's mutated forms seems to be destabilized in the heart of HCM patients harbouring a CSRP3 missense mutation. We also present evidence of mild skeletal muscle disease in affected persons. Our results support the view that HCM is not exclusively a sarcomeric disease. We suggest that impaired mechano-sensory stress signalling might be involved in the pathogenesis of HCM.
Abstract: This report describes the reversal of a cardiac resynchronization therapy non-responder status in a patient with a surgically placed left ventricular lead by the use of a newly available active fixation coronary sinus lead.
Abstract: Aims Chronotropic incompetence (CI) in patients with congestive heart failure (CHF) develops frequently under beta-blocker and amiodarone therapy. It can be corrected by pacing. We performed a randomized study to test whether pacing is beneficial in CHF patients with CI. Methods and results Congestive heart failure patients under combined beta-blocker and amiodarone therapy (n = 77) were randomly assigned to inhibited pacing (INH; basal rate 40 bpm/hysteresis 30 bpm; n = 38) or to DDDR pacing with optimized atrioventricular delay (OPT; stimulation rate 65-120 bpm, n = 39). Groups showed similar baseline values in NYHA class, heart rate, and ejection fraction (EF) and were followed up to 10 years. The resting and mean 24 h heart rate after 1 year decreased by -2.6/-5 bpm in INH, but increased by +3.6/+6.0 bpm in the OPT group (P < 0.001). The QRS interval after 1 year increased by 12 +/- 23 ms in the INH group, but +32 +/- 36 ms in the OPT group (P < 0.01). Patients with INH developed a greater left ventricular EF (LVEF) when compared with OPT patients (+10.6 +/- 8 vs. +2 +/- 10%, respectively; P = 0.04). Changes in LVEF were negatively correlated with heart rate, but not with QRS width changes. Prognosis and the event rate were better in the INH group. Conclusion In the long-term follow-up, single-site ventricular pacing in patients with CHF and low LVEF is associated with significant clinical events and a poor prognosis.
Abstract: Aims Cardiac resynchronization therapy (CRT) has become a standard therapy in cases of heart failure and asynchrony. Unfortunately, 20-30% of patients were non-responsive (NR) to CRT. In this report we used cardiac contractility modulation (CCM) as an adjunctive measure in NR patients. Methods and results Sixteen NR patients, mean age 65 +/- 9 years, mean ejection fraction 27.3 +/- 7.4%, and New York Heart Association (NYHA) class III (n = 9) or IV (n = 7) despite CRT plus optimized medical therapy, received an additional CCM-implantation contra-lateral to the existing CRT system (OPTIMIZER III, Impulse Dynamics, Orangeburg, NY, USA). Cardiac contractility modulation delivers non-excitatory high-energy stimulatory impulses during the absolute refractory period, thus improving contractility [left ventricular (LV) dp/dt)] by stimulating the septum with two screw-in leads and one additional atrial lead for triggering the impulses. Acute LV dp/dt changes induced by CCM stimulation were measured by 5F Millar catheters placed in the LV during the implantation procedure in 14 of 16 cases. Patients were followed prospectively. Left ventricular dp/dt increased from a mean of 568 +/- 153 to 646 +/- 147 mmHg/s (+14%, P < 0.001) in the acute intraoperative testing. We noted the following complications and events during a follow-up of an average of 147 +/- 80 days (range 68-326) after CCM: intraoperative ventricular flutter needing cardioversion (n = 1), atrial lead dislocation (n = 1), coronary sinus (CS) lead dislocation (n = 1), painful stimulation requiring repositioning of septal leads (n = 1), true defibrillator shocks (n = 3), cardiac decompensations (n = 3), atrial fibrillation (n = 4), renal failure (n = 1), and pneumonia (n = 2). NYHA class improved from 3.4 to 2.8 (P < 0.01), and the ejection fraction increased from 27.3 +/- 5 to 31.1 +/- 6 (P < 0.01). Three patients (19%) died suddenly presumably due to electromechanical dissociation after 318, 104, and 81 days. No electrical interference was observed between the CCM and CRT systems, and in particular, at no time was the CRT-implantable cardioverter-defibrillator found to be delivering inadequate shocks. Conclusion The CCM method is feasible and could be applied with calculated risks as a possible useful adjunct in CRT-NR when no other options are available; however, mortality and event rates are high in this very sick population.
Abstract: Growth hormone and its mediator insulin-like growth factor 1 (IGF1) exert various actions on the growth and proliferation of myocardium and many other cell types. IGF1 is predominantly bound to at least six binding proteins (IGFBP1â6). Growth hormone is the major hormonal factor controlling IGF1 and IGFBP concentrations. Tissue concentrations, bioavailability and effects of IGF1 are regulated by modifications of IGFBP affinities through proteolysis, phosphorylation and binding to cell surfaces.1
In a failing myocardium, growth hormone and IGF1 improve cardiac haemodynamics, normalise the calcium homoeostasis and support an efficient myocardial energy metabolism.2 However, analyses of the IGF1 serum levels in patients with congestive heart failure (CHF) from different causes showed increased as well as unchanged levels. Furthermore, despite improvements of cardiac function in several small open growth hormone-substitution studies, these effects could not be confirmed in two large randomised double-blind studies.2 Nevertheless, we observed a marked increase of the left . . .
Abstract: Cardiac resynchronization therapy (CRT) using coronary sinus (CS) leads is an established method for the therapy of congestive heart failure (CHF) in the case of asynchronous ventricular contractions. Successful therapy depends on the placement of left ventricular leads usually via the coronary sinus (CS), a technically more challenging procedure than regular pacemaker implantations. Without specific precautions CRT implantation can be the gateway to a time consuming nightmare. Therefore CS lead implantation methods, with a focus on complications, were reviewed according to the literature and own experience with approximately 500 procedures from 1999-2007.
Abstract: AnläÃlich des 35. Jährigen Bestehens der Arbeitsgemeinschaft Herz-Kreislauf Hamburg
(HerzInForm) soll die Geschichte der Hamburger Arbeitsgemeinschaft Herz/Kreislauf und die aktuelle Situation der Bewegungsbehandlung bei kardiologischen Patienten beschrieben werden. Die Idee einer engen Verzahnung von Akutkrankenhaus, Rehabilitationseinrichtung und wohnortnaher Betreuung in Herzsportgruppen hat als so genanntes âHamburger Modellâ Medizingeschichte geschrieben und stellt in der Phase III trotz aller Hemmschuhe durch Politik und Kostenträger nach wie vor die Basisbehandlung aller herzkranken Patienten dar. In Hamburg werden derzeit mehr 3800 Patienten in 160 Herzgruppen betreut (in Deutschland existieren über 6000 Gruppen). Dass jetzt auch die physiologischen Wirkungen einer Bewegungstherapie detailliert aufgeklärt werden konnten und für Bewegung neben der bekannten Steigerung der Lebensqualität ein Ãberlebensvorteil bewiesen wurde, ist umso mehr Ansporn die Aktivitäten in dieser Richtung noch zu verstärken. Dies wenn nicht als Alternative, so aber doch im Rahmen von Netzwerken mindestens als komplementäre Ergänzung zu Pharmakotherapie, Koronarintervention und Chirurgie.
Abstract: Rhabdomyolysis is a well known side effect of statin therapy. Several drugs may increase its risk by drug-drug interactions. In particular, patients with heart disease receive more and more different compounds to cope with all the pathomechanisms involved and may therefore be of high risk for side effects. We report a case of rhabdomyolysis in a patient with heart failure on a multi-drug regimen caused by a drug interaction between chronic statin therapy (simvastatin), amiodarone and newly administrated digitoxin. The patient recovered fully after cessation of simvastatin therapy, the other drugs were given continuously. Potential mechanisms of this event are discussed. Most interesting in this case is that rhabdomyolysis occurred only after starting digitoxin after long-term therapy with the statin.
Abstract: Cardiac Resynchronization therapy (CRT) using coronary sinus (CS) leads is an established method for the therapy of congestive heart failure (CHF) in the case of inter- and intraventricular conduction delays. However implantation of CS leads is somewhat challenging due to a high number of peri- or postoperative dislocations at a rate of about 10%. The retained guidewire technique has been proposed for the implantation of coronary sinus leads for stabilization in case of repetitive intraoperative dislocations. This report describes CS lead and guidewire fracture 2 years after such an implant.
Abstract: AIMS: To evaluate the utility of intrathoracic impedance monitoring for detecting heart failure (HF) deterioration in patients with an implanted cardiac resynchronization/defibrillation device. METHODS AND RESULTS: Patients enrolled in the European InSync Sentry Observational Study were audibly alerted by a device algorithm if a decrease in intrathoracic impedance suggested fluid accumulation. Clinical HF status and device data were assessed at enrolment, during regular follow-up, and if patients presented with an alert or HF deterioration. Data from 373 subjects were analysed. Fifty-three alert events and a total of 53 clinical events (HF deterioration defined by worsening of HF signs and symptoms) were reported during a median of 4.2 months. Adjusted for multiple events per patient, the alert detected clinical HF deterioration with 60% sensitivity (95% CI 46-73) and with a positive predictive value of 60% (95% CI 46-73). Higher NYHA class at baseline was predictive for adequate alert events during follow-up (P < 0.05). In 11 of 20 HF deteriorations without preceding alert, an upstroke of the fluid index occurred without reaching the programmed alert threshold. CONCLUSION: A device-based algorithm that alerts patients in case of decreasing intrathoracic impedance facilitates the detection of HF deterioration. Future randomized, controlled trials are needed to test whether the tailored use of intrathoracic impedance monitoring can improve the ambulatory management of patients with chronic HF and an implanted device.
Abstract: AIMS: Stored electrograms or marker channels are available in most of modern cardiac pacemaker models. We sought to analyse these information to uncover terminal events of pacemaker patients dying suddenly. Method and results We made post-mortem pacemaker (PM) interrogations in 19 patients dying suddenly out of hospital between the years 1997 and 2005 (mean age 59 +/- 13 years, 90% males). The systems had activated arrhythmia monitoring algorithms. Indications of pacing were sick sinus syndrome in seven, AV-block in five, and heart failure due to asynchrony in seven cases. The interrogated pacemakers were CHORUS 7034 (n = 12), CONTAK TR (n = 2), and INSYNC III (n = 5). For interpretation stored marker channels and electrograms were analysed. The mean observation time after PM implantation prior death was 2.11 +/- 1.44 years, the mean left ventricular ejection fraction from the last available echo examination in the year prior death was 27.5 +/- 8%, mean age was 63 +/- 12 years. In 17/19 cases (89%), a tachycardia (most likely ventricular tachycardia) was found correlating to the time of death. The mean cycle length of the terminal arrhythmia was 307 +/- 144 (250-344) ms, corresponding to a heart rate of 195 +/- 95 (174-240) bpm. We found no evidence of specific pacemaker-related problems such as electronic failure, battery depletion, or undersensing. CONCLUSIONS: Post-mortem analysis of arrhythmia monitoring of pacemaker patients revealed tachycardias (most likely ventricular tachycardia) to be related to sudden death. These findings give some insight in mechanisms of terminal events in this group.
Abstract: Cardiac resynchronization therapy (CRT) is a new method for the correction of inter- and/or intraventricular conduction delays of patients with heart failure. The long-term impact of CRT on central hemodynamics is not fully characterized. We performed complete right heart catheterization studies in 31 patients receiving a CRT device pre and 6 months after implantation. Most of the patients improved in their NYHA stage, their LVEF, and in parallel showed reduced right atrial (RA) pulmonary artery (PA) and pulmonary capillary wedge (PCW) pressures and pulmonary vascular resistance both at rest and at 25 watts. In addition, we found a reduction in heart rate accompanied by an increased mean arterial pressure both at rest and at 25 watts. Accordingly, brain natriuretic peptide levels (BNP) were lowered. It was concluded that, besides other well-known effects on ventricular coordination, central hemodynamics after 6 months were improved during CRT.
Abstract: AIMS: Coronary sinus (CS) lead implantation is a technically challenging procedure owing to variable vein anatomies and a high dislocation rate. Therefore, CS lead technology has undergone evolutionary changes during the last 10 years. The mode of fixation has been a passive one up to now. We want to describe our first clinical experience with the newly available active fixation lead 4195 in terms of dislocation rate and stability of thresholds compared with conventional models. METHODS AND RESULTS: From 1999 to February 2007, we implanted 403 CS leads in 368 patients. Leads were categorized into three different groups on the basis of their fixation mechanism: straight (Easytrak I and Situs OTW; n = 54), curved (Attain 4193 and 4194, Corox, Aescula, Situs ULD; n = 308), and active (Attain 4195; n = 41). Operative and follow-up data were prospectively noted and checked for significance between groups during the first 3 months after implantation. Kaplan-Meier analysis of long-term lead function was also performed. Straight and curved CS leads suffered from significantly more dislocations compared with active fixation (P < 0.001). The active fixation lead (4195) has a stable threshold over time compared with a significant rise after 24 h and thereafter in straight (62%) and curved leads (20%). However, retraction of an active fixation CS lead may be a difficult issue as outlined in two cases requiring pullback of a 4195 lead owing to phrenic nerve stimulation (one unsuccessful despite vigorous traction). CONCLUSION: The active fixation lead 4195 using retention lobes yielded stable thresholds over time and seems to be superior to conventional leads in terms of dislocation. However, extraction may be a difficult or even impossible task.
Abstract: Cardiac resynchronization therapy (CRT) using coronary sinus (CS) leads for biventricular stimulation is an established method for the therapy of congestive heart failure (CHF) in the case of inter- or intraventricular conduction delays. There are some patients having two separate devices: an ICD and a biventricular pacemaker. This case report describes an unusual interaction of these systems: an inappropriate VVI defibrillator shock during left ventricular threshold measurement in a biventricular pacemaker implanted on the other side.
Abstract: INTRODUCTION: Cardiac resynchronization therapy (CRT) using coronary sinus (CS) leads is a new method for the therapy of congestive heart failure (CHF). Because the intervention is more complex than regular pacemaker implantations, information on the feasibility and side effects of this method are of interest. METHODS: From 1999 to June 2005, CRT implantations were attempted in 244 patients (pts; mean age 64+/-12 years, range 14-90 years), 82% were male, 44% had coronary artery disease, 29% were in atrial fibrillation, 71 had preexisting pacemakers. RESULTS: In 97% of the pts the intervention was successful (27% of the systems with defibrillation capabilities). In 285 interventions, 255 CS leads were positioned according to CS vein anatomy in 130 posterolateral, 97 anterolateral and 28 anterior side branches (16 patients received 2 CS leads). Over-the-wire leads were used in 88%, 71% were additionally preshaped. We observed no mortality but 37 complications (12.5%): CS dissection in 9, CS perforation in 1, ventricular fibrillation in 4, asystole in 5, pulmonary edema in 1, pneumothorax in 2, need for early CS lead revision in 19 (dislodgement n=7, phrenic nerve stimulation n=12) and infection with explantation in 2 cases. An improvement in NYHA functional class was found in 88% of pts (only 55% if anterior lead position). CONCLUSION: Perioperative complications during CS lead implantation occur in 10-15% of cases. Most patients responded well to CRT. Patients should be informed about the possible need for a reoperation. During implantation, immediate defibrillation and stimulation capabilities must be available. Anterior lead positions should be avoided.
Abstract: BACKGROUND: Elevated pulmonary vascular resistance (PVR) is relevant to prognosis of congestive heart failure and heart transplantation. Proof of reversibility by pharmacologic testing in potential transplantation candidates is important because it indicates a reduced probability of right ventricular failure or death in the early post-transplant period. This study aimed to clarify the possible extent of acute reversibility of elevated PVR in a large, consecutive cohort of heart transplant candidates. METHODS: This study included 208 consecutive patients (age 52 +/- 10 years, 89% men and 11% women, ejection fraction 21 +/- 9%, Vo2max 12.6 +/- 4.2 ml/kg/min) being evaluated for heart transplantation in 7 transplant centers in Germany and Switzerland. Testing was performed with increasing intravenous doses of prostaglandin E1 (PGE1; average maximum dose 173 +/- 115 ng/kg/min for at least 10 minutes) in 92 patients exhibiting a baseline PVR of > 2.5 Wood units (WU) and/or a transpulmonary gradient (TPG) of > 12 mm Hg. RESULTS: PGE1 testing lowered PVR from 4.1 +/- 2.0 to 2.1 +/- 1.1 WU (p < 0.01), increased cardiac output from 3.8 +/- 1.0 to 5.0 +/- 1.5 liters/min (p < 0.01), and decreased TPG from 14 +/- 4 to 10 +/- 3 mm Hg (p < 0.01), mean pulmonary artery pressure (PAM) from 39 +/- 9 to 29 +/- 9 mm Hg (p < 0.01) and mean pulmonary capillary wedge pressure (PCWP) from 24 +/- 7 to 19 +/- 9 mm Hg (p < 0.01). Mean aortic pressure (MAP) decreased to 85% and systemic vascular resistance (SVR) to 65% of baseline values (p < 0.01). Symptomatic systemic hypotension was not observed. For the whole population the percentage of patients with PVR > 2.5 WU was reduced from 44.2% to 10.5% with PGE1. PVR decreased in each patient; only 2 patients (1%) remained ineligible for listing because of a final PVR of > 4.0 WU. TPG, ejection fraction and male gender were independent predictors of reversibility of PVR. CONCLUSIONS: Elevated PVR in heart transplant candidates is highly reversible and can be normalized during acute pharmacologic testing with PGE1.
Abstract: BACKGROUND: One-third of cases of dilated cardiomyopathy (DCM) is of familial aetiology. Several genes have been reported to cause the autosomal dominant form of DCM. AIMS: To analyze the lamin A/C gene (LMNA) in 31 unrelated patients with DCM and conduction system disease (CSD). METHODS: Patients and family members underwent physical examination, ECG/Holter-ECG, echocardiography, and selective coronary angiography. Genetic analysis of all coding exons of LMNA was performed using PCR and sequencing. RESULTS: Three different LMNA mutations (Arg377His, c.1397delA, c.424_425ins21nt) were identified in three families with autosomal dominant disease comprised of 39 individuals. 21 individuals were mutation carriers, of whom 12 were symptomatic. We observed a progressive and age-dependent form of DCM with CSD and arrhythmias. First, the patients developed a moderate left ventricular dilatation without symptoms. Later, systolic function declined progressively and the patients became symptomatic resulting in a high mortality due to sudden death and heart failure. CONCLUSIONS: Genetic screening leads to the identification of symptomatic and asymptomatic mutant carriers. The latter at a young age should be regarded as "presymptomatic" because of the age-dependent disease manifestation. New guidelines are required for the management of these individuals.
Abstract: BACKGROUND: Acute studies in cardiac resynchronization therapy (CRT) showed that hemodynamic effects may depend on the coronary sinus (CS) lead position. However, there are no data on the longterm effect of CS lead position. METHODS: In 45 heart failure patients with left bundle branch block and QRS >150 ms (age 59+/-10 years, 17 dilative cardiomyopathy, 23 ischemic, 5 valvular), biventricular pacemakers were implanted. CS leads were positioned in posterior (P, n=15), lateral (L, n=19) or, if no other option available, anterior (A, n=11) side branches. Before and 6 months after implantation, clinical state, echocardiography, brain natriuretic peptide (BNP) and right heart catheterization were evaluated. RESULTS: Baseline parameters were similar between groups. After 6 months, there were 32/34 responders in groups P and L compared to 7/11 responders in group A (94 vs groups P and L: Arterial pressure +8 and +9% vs +2%; PCWP -23 and -15% vs -4%, pulmonary pressure -18 and -12% vs -3% (p<0.01 for A vs P+L); cardiac index +21 and +12% vs +11% (p=0.03 for A vs P). BNP was reduced by 55, 35, and 27% (p=0.05 for A vs P). Ejection fraction increased in P and L by 40 and 41%, respectively, but only by +19% in A (p<0.03 for A vs P+L). CONCLUSION: Chronic CRT improves ejection fraction, BNP and hemodynamic measurements predominantly in patients with lateral and posterior CS lead positions. Anterior lead positions should be avoided.
Abstract: This report illustrates the case of a patient with an implantable cardioverter defibrillator (ICD) who during physiotherapy with transcutaneous electrical stimulation of the lumbar musculature perceived a shock discharge by the ICD. Analysis of the stored electrogram showed inappropriate therapy due to electromagnetic interference with the external stimulation. Patients as well as physiotherapists should be informed about this potential interaction to avoid such iatrogenic, inappropriate ICD therapy.
Abstract: We describe a 30-year-old man with end-stage heart failure after therapy with mitoxantrone for multiple sclerosis. A successful orthotopic heart transplantation was performed when intensified medical therapy failed to improve the patient's hemodynamics. In spite of the severe underlying disease he did well on dual immunosuppression with methylprednisone and cyclosporine. Neurologic symptoms remained stable throughout the procedure and, after 2 months, he resumed preoperative ambulatory status. Eight years after the operation, the patient is now in New York Heart Association (NYHA) Class I status. Using canes, he is able to walk short distances. Repeated urinary tract infections caused by Escherichia coli became a problem, but have been controlled by long-term oral antibiotic prophylaxis with trimethoprim.
Abstract: AIMS: This comparative prospective multi-centre study evaluated efficacy and safety of cyclosporine A downtitration in heart transplant recipients with chronic renal dysfunction potentially attributable to cyclosporine (n=161). METHODS: In the intervention arm (n=109, recruited from 9 centres), mycophenolate mofetil was introduced de novo or substituting azathioprine, followed by cyclosporine reduction (target trough levels 2-4 microg/ml and 50 ng/ml, respectively). In controls (n=52, recruited from 1 centre), immunosuppression remained unchanged. Renal function was recorded twelve, six, and three months before, and throughout the eight-month study period. RESULTS: At study entry, cyclosporine trough levels and renal function parameters were comparable. At study end, mean+/-SD cyclosporine in the intervention arm was 57+/-24 vs. 116+/-36 ng/ml in controls. During the study, creatinine decreased by 23.3+/-50.7 micromol/l (P<0.0001) in the intervention arm but increased by 7.3+/-46.9 micromol/l (P=0.992) in controls (P=0.0001 for comparison between groups). A creatinine reduction of at least 20% was found in 35% of subjects of the intervention arm but only in 4% in the control arm (P<0.0001 for comparison between groups). Improvement in renal function was not weakened after adjustment for baseline characteristics in multiple regression analysis. Renal function improved in strata of creatinine entry values from 150 to 310 micromol/l, regardless of the presence of diabetes. Myocardial biopsies at target levels for cyclosporine and mycophenolate mofetil showed three reversible subclinical rejection episodes. CONCLUSIONS: Cyclosporine downtitration improved renal dysfunction in diabetic and non-diabetic heart transplant recipients across a wide range of creatinine levels. The long-term benefit of this strategy deserves further study.
Abstract: Computerized heart allograft recipient monitoring (CHARM) is a unique concept of patient surveillance after heart transplantation (HTx), based on the evaluation of intramyocardial electrograms (IEGMs) recorded non-invasively with telemetric pacemakers. Previous open, single-center studies had indicated a high correlation between CHARM results and clinical findings. The present study was initiated to assess the suitability of CHARM for monitoring the absence of rejection in a blind, multicenter context. During the HTx procedure, telemetric pacemakers and two epimyocardial leads were implanted in 44 patients at four European HTx centers. IEGMs during pacing were recorded and transferred via the Internet to the CHARM computer center, for automatic data processing and extraction of diagnostically relevant information, i.e., the maximum slew rate of the descending part of the repolarization phase of the ventricular evoked response (VER T-slew). The study period comprised the first 6 months after HTx, during which the transplant centers were blind to the CHARM results. A single threshold diagnosis model was prospectively defined to assess the ability of the VER T-slew to indicate clinically significant rejection, which was defined as an endomyocardial biopsy (EMB) grade greater than or equal to 2, according to the grading system of the International Society for Heart and Lung Transplantation. All EMB slides from three centers were reviewed blind by the pathologist of the fourth center in order that agreement among the histological diagnoses at the various centers could be assessed. Totals of 839 follow-ups and 366 EMBs were obtained in 44 patients. Thirty-seven patients were alive at the end of the study period. Age at HTx, EMB grade distribution, and rejection prevalence varied significantly between the centers. Review of the EMB results showed considerable differences with respect to classification of significant rejection. Comparison of average VER T-slew values with and without rejection in the 15 patients who exhibited both states revealed significantly lower values under the influence of rejection (97+/-13% vs 79+/-15%, P<0.0001). Twenty out of the 25 cases with significant rejection were correctly identified by VER T-slew values below a threshold of 98% (sensitivity =80%, specificity =50%, negative predictive value =97%, positive predictive value =11%; P<0.0005). Of the EMBs, 48% could have been saved if the diagnosis model had been used to indicate the need for EMB. A high negative predictive value for the detection of cases with significant rejection has been obtained in a prospective, blind, multicenter study. The presented method can, therefore, be used to supplement patient monitoring after HTx non-invasively, in particular to indicate the need for EMBs. In centers with patient management similar to the ones who participated in the study, this may allow a reduction in the number of surveillance EMBs.
Abstract: A 66-year-old patient with terminal heart insufficiency (NYHA IV) received maximum medical therapy, but was also in need of an implantable-cardioverter-defibrillator (ICD). The ICD functioned flawlessly for the whole duration of implantation. It reverted several ventricular tachycardias with anti-tachycardial pacing alone, whereas some needed cardioversion as well. The patient died on the fourth day of hospitalization for a routine check of his ICD. The post-mortem examination revealed, that the ICD was deactivated and that the data had been erased after the patient's death. By reading off the raw data still stored within the ICD, the erased information could be restored. The stored EGMs showed traces of old ICD interventions as well as a permanent deactivation provoked by exposition to a magnetic field just hours before the patient's death. The problem of archiving and documenting the volatile electronic data inside the ICD is discussed. The need of a full autopsy after telemetric reading of the ICD data, including the explantation of the ICD aggregate and electrodes, as a means of quality assurance and under forensic aspects is emphasized.
Abstract: BACKGROUND: Pacemaker infection or some lead dysfunctions are an indication for removal of all foreign material. The use of laser energy is a new method for extraction of fixed leads that have been in place for a long time. There are only a few reports on results and complications of laser extraction in comparison to conventional methods. Therefore, this study compares results of laser lead extraction and conventional methods. METHODS: Since January 1999 we have made use of the laser lead extraction system of Spectranetics, Inc. Inner traction of the leads was performed using a "lead locking device" (LLD) and for laser application 12, 14 und 16 French "laser sheaths" were used. As the energy source, an excimer laser device was used (CVX-300). The intervention was performed under heart-lung machine backup. Results of the laser procedure in 24 patients and 45 leads (including 3 defibrillator leads) are compared to results of manual traction (23 patients, 53 leads), traction devices (24 patients, 38 leads), snare catheters (6 patients, 6 leads) and thoracotomy (5 patients, 9 leads) from the years 1995-1998. RESULTS: The mean operation time of the laser method (93 +/- 50 min) was not significantly different from manual traction (82 +/- 48 min,) or traction devices (100 +/- 45 min). The mean fluoroscopy time (9.4 +/- 50 min) was similar to traction devices (8.4 +/- 5 min, p < 0.05). In one patient a percardial tamponade developed with the need for urgent thoracotomy. This patient died on the fourth postoperative day due to cerebral hypoxia. The other 23 patients had an uneventful course. All but one lead could be removed without fragmentation, including a malpositioned lead in the left ventricle (success rate 96%). In 62 patients and 97 conventional extractions (53x manual, 38x device, 6x snare) from 1995-1998, one fatal (sepsis due to lead fragmentation) and four severe complications developed (pericardial tamponade, pulmonary abscess, pulmonary embolism, sepsis). In 15/62 patients with conventional methods, lead fragments remained (success rate 76%). Of five patients from 1995-1998, in whom leads with vegetations or tricuspid valve insufficiency were removed by thoracotomy and cardiopulmonary bypass, one patient died perioperatively. CONCLUSIONS: In contrast to conventional methods, excimer laser pacemaker or defibrillator lead extraction allows total removal of all foreign material. This prevents late complications from lead fragments left in place. However, life-threatening complications can occur with conventional as well as with the laser method. Therefore, this intervention should be done only in specialized centers using extended monitoring (invasive blood pressure, TEE).
Abstract: Routine intraoperative transesophageal echocardiography (TEE) revealed a previously undiscovered ventricular positioning of an infected ventricular lead left in place for 10 years. This case report describes successful removal of this lead from the left ventricle by means of excimer laser and discusses some important aspects to be considered.
Abstract: Heart transplantation is an established technique in the treatment of end-stage heart failure. Due to the scarcity of suitable donors, cardiac replacement should be limited to patients not responding to medical therapy and with no other surgical option. In this situation transplantation is urgent and the assignment of a suitable donor must be independent of total waiting time. In a regionally based cooperation of 4 northern German centers regarding donor allocation and heart transplantation, it has been demonstrated over a period of 44 months including 255 heart donors and 151 heart transplantations, that with a regional allocation system, waiting time for transplantation could be decreased to approximately 3 months, with excellent survival during the waiting period as well after transplantation. In addition, due to the close cooperation of the transplant centers involved, it allows for graft allocation in higher urgency situations within an acceptable time span. Although 56% of the organs were used locally, about one third of the donors could be offered to the Eurotransplant International Foundation (ET). The total number of transplants in each center was not increased significantly after initiation of this regional cooperation. The number of donors per month and the percentage of multiorgan resp. heart donors was stable, except for a decrease in 1997/1998. Regarding the import-export balance, 3 times more organs were exported out of the region than imported into it.
Key words: Heart transplantation, regional donor allocation, waiting time, Eurotransplant
Dr. S. W. Hirt
Klinik für Herz- und GefäÃchirurgie
Christian-Albrechts-Universität Kiel
Arnold-Heller-Str. 7
D-24105 Kiel
E-mail: shirt@kielheart.uni-kiel.de
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PABST SCIENCE PUBLISHERS
Lengerich, Berlin, Riga, Rom, Wien, Zagreb
Abstract: BACKGROUND AND AIM OF THE STUDY: Aortic valve replacement with cryopreserved human pulmonary or aortic valves (homografts) is an attractive alternative to the implantation of mechanical valves or bioprostheses, as anticoagulation can be avoided and a near-normal anatomy restored. However, few reports exist on the long-term follow up of patients with this type of valve. METHODS: Between 1990 and 1997, a total of 64 homografts were implanted in 62 adults (mean age 42 +/- 12 years) with non-endocarditic valve lesions (insufficiency, n = 16; stenosis, n = 20; combined lesions, n = 12; redo, n = 16). In total, 23 pulmonary grafts (PG) and 41 aortic grafts (AG) were used. Valves were obtained from the European Homograft Bank in Brussels. Two patients with aortic homografts were lost to follow up; the others were examined clinically and echocardiographically at yearly intervals (mean 3.6 +/- 2.0 years). Children aged less than 16 years (n = 21), and patients receiving a homograft due to endocarditis (n = 28) or during a Ross procedure (n = 16) were excluded from the study. RESULTS: Three patients (5%) died due to early postoperative complications (two with AG, one with PG). Three PG had to be explanted due to primary malfunction, and five (total 35%) during further follow up due to severe aortic insufficiency (at a mean of 3.3 +/- 1.8 years). In contrast, all AG were functioning at the end of the observation period (log rank test, p = 0.0001, chi-square test 13.9). The mean echocardiographic degree of regurgitation for PG was significantly higher than for AG (2.2 +/- 1 vs. 0.75 +/- 0.7, p <0.0001). The peak transvalvular gradient did not differ between groups (PG 12.3 +/- 9 mmHg vs. AG 16.7 +/- 10 mmHg, p = NS). In respect of perioperative parameters, patients with PG showed a significantly higher body temperature during the first seven postoperative days (37.3 +/- 0.6 degrees C vs. 36.8 +/- 0.3 degrees C, p = 0.003). All three patients with acute graft malfunction in long-term follow up had a perioperative febrile response without overt bacterial infection. CONCLUSION: In contrast to grafts of aortic origin, pulmonary homograft valves should not be used for aortic valve replacement because of their high rate of malfunction, both acutely and chronically. Higher postoperative body temperatures should lead to further investigations of possible enhanced immunoreactions against pulmonary homografts.
Abstract: BACKGROUND: Carvedilol and at least in some studies, amiodarone have been shown to improve symptoms and prognosis of patients with heart failure. There are no reports on the outcome of combined treatment with both drugs on top of angiotensin-converting enzyme inhibitors (ACEI), diuretics and digitalis. METHODS AND RESULTS: In 109 patients with severe heart failure submitted for heart transplantation at one single center between the years 1996 and 1998 [left ventricular ejection fraction (LVEF) 24.6+/-11%, 85% males, 52% idiopathic dilated cardiomyopathy (DCM), mean observation time 1. 9+/-0.4 years] a therapy with low-dose amiodarone (1000 mg/week) plus titrated doses of carvedilol (target 50 mg/day) was instituted. In addition, patients received a prophylactic dual chamber pacemaker (PM) in order to protect from bradycardia and for continuous holter monitoring. The devices were programmed in back-up mode with a basal rate of 40 i.p.m. with a hysteresis of 25%. Significantly, more patients were in sinus rhythm after 1 year than at study entry (85% vs. 63%, P<0.01). In 47 patients, under therapy over at least 1 year, the resting heart rate fell from 90+/-19 to 59+/-5 b.p.m. (P<0.001). Ventricular premature contractions in 24-h holter ECGs were suppressed from 1.0+/-3 to 0.1+/-0.3%/24 h (P167 b.p.m. detected by the pacemaker (1.2+/-2.8 episodes/patient/3 months vs. 0.3+/-0.8 episodes/patient/3 months after 1 year (P<0.01). The LVEF increased from 26+/-10 to 39+/-13% (P<0.001). NYHA class improved from 3. 17+/-0.3 to 1.8+/-0.6 (P<0.001) as well as right heart catheterization data. From the total cohort, seven patients (6%) developed symptomatic documented bradycardic rhythm disturbances requiring reprogramming of their pacemakers to DDD(R)/VVI(R) mode with higher basic rates. Two of these patients developed AV block, four sinu-atrial blocks or sinus bradycardia and one patient had bradycardic atrial fibrillation. During the observation period five patients died (3 sudden, 1 due to heart failure and 1 due to mesenteric infarction). Two patients had undergone heart transplants. The 1-year survival rate (Kaplan-Meier) without transplantation was 89%. Compared to historic control patients with amiodarone only (n=154) or without either agent (n=283) this rate was 64 and 57% (P<0.01). CONCLUSIONS: Heart failure patients benefit from a combined therapy with carvedilol and amiodarone resulting in a markedly improved NYHA stage, an increase in LV ejection fraction, a stabilization of sinus rhythm, a significant reduction in heart rate, a delay of electrical signal conduction and a suppression of ventricular ectopies. Approximately 6% of patients under such a regime became pacemaker-dependent in the first year. Compared to historic controls prognosis was better and the need for heart transplantation was lower. The exact role of either agent in combination or alone should be clarified in larger randomized studies.
Abstract: The implantation of fresh or cryopreserved human heart valves (homografts) in aortic position is a tool in cardiac surgery since 30 years. Homografts are attractive alternatives to the implantation of mechanical or xenobiological prostheses, because anticoagulation can be avoided and a near normal anatomy can be restored. Physicians should know about the several kinds of grafts and operative techniques to adequately take care of the patients in follow-up. This overview on the literature covers methods of harvesting, preparation and conservation of homografts according to standard protocols of the European Homograft Bank in Brussels. Their use in the therapy of human valvular disease is discussed with special emphasis to operative techniques (subcoronary, root) and the Ross procedure and in pediatric surgery. Complications and aspects of postoperative care are discussed including immunologic phenomena. Homografts are useful tools for aortic valve replacement, especially in juveniles, in the presence of contraindications for anticoagulation and in endocarditis. Whereas aortic homografts have excellent long-term results, pulmonic homografts show a significant rate of malfunction. Further studies should be performed to clarify the role of the Ross operation or stentless xenografts compared to homografts in aortic position. In pediatric cardiac surgery homografts are of value especially for the reconstruction of the right ventricular outflow tract. Homografts in mitral position show disappointing results up to now. The major limitation in the use of homografts is the mismatch of availability and request, therefore homografts can only be used for the above mentioned special indications.
Abstract: BACKGROUND: CA 125, known as a marker for ovarian cancer with hypothetical but hitherto uncharacterized biologic functions, was reported to be elevated in some not-well-defined benign conditions. There are no reports on fluctuations of CA 125 related to cardiac function, especially the failing heart and neurohumoral factors such as norepinephrine or atrial natriuretic peptid/e. METHODS AND RESULTS: CA 125 blood levels were determined in patients with heart failure before and after heart transplantation (HTx). In 71 patients, parallel determinations of norepinephrine, atrial natriuretic peptide, pulmonary capillary wedge pressure, and right atrial filling pressure were done. CA 125 levels also were prospectively studied in patients with heart failure with stabilization (n = 25) or worsening of the clinical status (n = 9) and after HTx (n = 25). Parallel determinations of the tumor markers CEA, CA 199, CA 153, TPS, and TPA were also done. The results were grouped according to the clinical status (New York Heart Association class) of the patients. CA 125 was significantly correlated with neurohormones and filling pressures. Follow-up investigations revealed a decrease of CA 125 levels after HTx (401 +/- 259 U/L vs 33 +/- 22 U/L, P <.001, n = 25) or stabilization (429 +/- 188 U/L vs 78 +/- 35 U/L, P <.001, n = 25) and an increase during worsening of heart failure (42 +/- 25 U/L vs 89 +/- 32 U/L, P <.01, n = 9). In 4 patients after HTx, unexpected death was preceded by rising CA 125 levels. CEA, CA 199, CA 153, TPS, or TPA did not correlate with heart failure status or clinical events. CONCLUSIONS: CA 125 is a marker of the clinical and hemodynamic status and the course of patients with heart failure before and after heart transplantation. The determination of CA 125 serum levels may be an additional tool in the management of these patients. In patients with cancer, these "nonspecific" changes must be considered when CA 125 levels are determined. Whether CA 125 has a specific biologic role in heart failure deserves further studies.
Abstract: BACKGROUND: Due to the shortage of donor organs there is a long waiting time for heart transplantation. As a consequence, a high mortality rate on the waiting list diminishes the potential benefit of the procedure. Tailored medical therapy optimized according to the individual patients demands was introduced to select responding HTx candidates for continued management without transplantation. The development of modes of death over time (heart failure, sudden arrhythmic) in this population is unknown. METHODS: In 434 elective candidates for heart transplantation, submitted to our institution in the years 1984-1997 (50% coronary artery disease, mean age 51.6 +/- 12 years, 86% males) medical therapy was adjusted according to the results of repeated right heart catherizations. Adjuncts to conventional therapy with ACE inhibitors, digitalis and diuretics were amiodarone, beta-blockers, spironolactone, oral anticogulants, molsidomine or nitrates. Only patients not responding to these measures were processed to HTx. Clinical events (death, mode of death, HTx, resuscitation) were noted and analyzed by the Kaplan-Meier method and related to patients characteristics by multivariance analysis. RESULTS: During the mean follow-up of 2.36 +/- 2.4 years only 113 patients (25%) received a donor heart. One hundred-sixteen patients (26%) died without transplantation. Eighty-three (72%) of the deaths were sudden, 24 (20%) due to progression of heart failure and 9 (8%) due to other reasons. A shift from heart failure to sudden death was observed. Including 8 successful resuscitations due to documented VT/VF, there is a 20% risk of having a major arrhythmic event during the first two years of observation. Long-term (>1 year) medical responders had better hemodynamics at entry. Patients who died suddenly had similar clinical and hemodynamic data at entry than patients who needed an early transplant, but were in a comparable NYHA stage before death than long-term medical responders (2.15 +/- 0.8 vs 1.82 +/- 0.6, NS). Patients dying suddenly had significant more ventricular premature beats (1.6 +/- 2.9%/24 hours vs 1.06 +/- 2.8%/24 hours, p < .01) and complex ventricular arrhythmias (7.3 +/- 2.7/24 hours vs 1.98 +/- 5.6/24 hours, p < .01) than long-term responders. Seventy-five percent of all sudden death occurred during the first 2 observation years. CONCLUSIONS: The rate of heart failure death in elective candidates for heart transplantation under optimized medical therapy is low when patients are followed closely and transplant can be done rapidly after deterioration is recognized. Sudden death represents the highest risk for most patients. This event occurred predominantly in stable patients under tailored medical therapy without indication for HTx at that time. Our results strongly demand strategies for risk stratification and the investigation of prophylactic measures in this population.
Abstract: OBJECTIVE: We detected markedly decreased cyclosporin blood levels in a heart-transplanted patient after the gastrointestinal lipase inhibitor orlistat was accidentally added to the treatment program to control for his obesity. Therefore, we determined cyclosporin plasma concentration time kinetics with and without orlistat reexposition in this patient. METHODS: Plasma concentration time kinetics of whole blood cyclosporin levels in an obese heart-transplant patient were measured using a standard monoclonal fluorescence polarisation immunoassay. Results were obtained in hourly intervals up to 12 h without and with co-therapy of 3 x 120 mg orlistat (Xenical, Roche Ltd., Switzerland). The orlistat re-exposition was started the day before taking blood samples. RESULTS: Cyclosporin trough levels (98 ng/ml vs 52 ng/ml), maximum concentrations (532 ng/ml vs 74 ng/ml) and the area under the blood drug concentration-time curve (2832 ng h ml-1 vs 700 ng h ml-1) were greatly reduced with orlistat. CONCLUSIONS: Orlistat markedly decreased blood cyclosporin concentrations, possibly due to an interference with its absorption in the small intestine. To avoid potential dangerous under-immunosuppression, orlistat should not be used in patients taking cyclosporin.
Abstract: BACKGROUND: Because the risk of developing malignant tumors after heart transplantation is approximately 100-fold higher, methods for rapid diagnosis must be developed to allow early and aggressive treatment in these patients. Although tumor markers have been used frequently for surveying already detected cancer, we studied their value in screening for tumors in heart transplant patients. METHODS: The levels of the tumor markers CEA, CA19-9, CA125, CA72-4, TPA, TPS, and CYFRA 21-1 were determined prospectively in 3-month intervals in 91 heart transplant patients between 1993 and 1998. RESULTS: In eight patients a definite diagnosis of cancer was made during the marker survey (mean observation time 2.85 +/- 1.3 years), including bronchogenic carcinoma in six, renal carcinoma in one, and colon cancer in one. All patients with bronchogenic carcinoma were smokers. The markers had a sensitivity below 60% to detect cancer. Given a 2-fold cutoff level (10 ng/mL), the CEA was the only marker with sufficient specificity (93.8%, only one false-positive result). Two patients were symptom-free even though they had elevated CEA levels. In one of those patients, disseminated intractable cancer was diagnosed at first evaluation, whereas no tumor was found in the other case at first evaluation. Subsequently, by means of fluorodeoxyglucose positron emission tomography, a hypermetabolic region was found in the right upper mediastinum. Control computed tomographic scan 4 weeks after the first investigation showed disseminated intractable disease also in this patient. Another heart transplant patient with colon cancer showed a normalization of the CEA after hemicolectomy and an increase in the CEA when liver dissemination developed. There was a relationship between cardiac death and CA125 and TPS in some heart transplant patients. CONCLUSIONS: We conclude that the CEA is the only tumor marker with adequate sensitivity and specificity to detect subclinical malignancies in the follow-up of heart transplant patients. However, because of several limitations (limited diagnostic and therapeutic possibilities and enormous costs), we cannot recommend screening by tumor markers on a regular basis. Because of the elevated risk of cancer in patients who had organ transplantation, further prophylactic measures, especially smoking cessation programs, must be developed. Once a malignancy is diagnosed, tumor markers can help target clinical decisions. Additionally, nonspecific increases in CA125 and TPS levels might be related to nonmalignant circulatory disturbances and cardiac death.
Abstract: BACKGROUND: Elevated plasma levels of tumor markers may be caused by diseases other than malignancy, i.e. kidney, liver or circulatory disturbances. These conditions are not well defined, especially since there are only sparse reports on fluctuations of tumor markers related to cardiac function. PATIENTS AND METHODS: During our routine pre- and postoperative follow-up tumor marker determinations in heart failure patients were made in order to screen for possible occult neoplasm's which may either be a contraindication or a sequela of heart transplantation. The markers CA 12-5, CEA, CA 19-9, CA 72-4, TPA, TPS and CYFRA 21-1 were determined at three month intervals, besides clinical examination and hemodynamic measurements in a total of n = 118 patients pre- and n = 74 patients post heart transplantation. RESULTS: The results were grouped according the clinical status (NYHA-stage 1-4): CA12-5 (29.4 +/- 40.63 omega 151, 174 +/- 345 and 491 +/- 633 U/ml, p < 0.001 between all groups) and TPS (64 +/- 32, 118 +/- 153, 163 +/- 311 and 181 +/- 232 U/ml, p = 0.06 between all groups) were increasingly elevated in NYHA stages 1, 2, 3 or 4 respectively. A direct correlation to right atrial pressure (r = 0.41, p < 0.0001) and pulmonary capillary wedge pressure (r = 0.27, p < 0.001) was only found for CA 12-5. After heart transplantation a normalization of elevated pre-OP levels could be found. Comparable to heart failure patients poor graft function was also associated with elevated levels of CA 12-5 (113 +/- 99 vs 21.6 +/- 31 U/ml, p < 0.0001), CA 72-4 (8.4 +/- 3 vs 3.6 +/- 4, U/ml p = 0.03) and TPS (154 +/- 133 vs 66 +/- 28 U/ml, p < 0.001). The individual time course of the markers, especially of CA 12-5, correlated nicely to clinical events and hemodynamic measurements in some patients. Another finding was that CYFRA 21-1 levels were correlated to renal function. CEA, CA 19-9 and CYFRA 21-1 serum levels were not influenced by circulatory disturbances. CONCLUSION: We concluded that the tumor markers CA 12-5 and TPS (but not CEA, CA 19-9 and CYFRA 21-1) are associated with congestion and the clinical course of heart failure and HTx patients. These "nonspecific" changes have to be considered when tumor markers are determined in cancer patients with heart failure. Whether CA 12-5 blood levels may yield additional prognostic information in the management of cardiovascular patients has to be determined in further studies.
Abstract: BACKGROUND: Exercise capacity after heart transplantation (HTx) may be limited by sinus node disease of the donor heart and atrioatrial dissociation. The role of pacemaker therapy in this setting is not well defined. The purpose of this study was to compare clinical and hemodynamic data of heart transplant recipients with acquired sinus node disease treated with atrial synchronized pacing and patients with other pacing modes or without pacemakers 1 year after operation. METHODS: Our cohort comprises a total of 112 HTx recipients from the years 1984 to 1996. Atrial synchronized pacing was performed in 21 patients with donor sinus node disease and recipient sinus rhythm. There was no associated morbidity or death for the pacemaker implantation. Fourteen patients received a dual-chamber pacemaker programmed with a short atrioventricular-Delay in A2A2D mode (donor atrial pacing triggered by recipient atrial sensing or both atria stimulated on demand); in the last 6 consecutive patients a single-chamber pacemaker was implanted with two unipolar leads to the atria connected with a Y adapter programmed in A2A2T mode (both atria were sensed and stimulated by triggering each other). RESULTS: Signals and thresholds remain stable over time. When clinical and hemodynamic data of 12 A2A2D/T patients with complete 1 year follow-up were compared to age- and sex-matched control HTx recipients with other pacing modes or without pacemakers, a significant benefit of atrial synchronization could be shown regarding rise in heart rate response to exercise (+38% vs 30% vs 16% at 50 watt), New York Heart Association classification (1.6 vs 1.8 vs 2.2), Roskamm staging (1.3 vs 2.5 vs 1.5), cardiac index at rest (3.2 vs 2.78 vs 3.1 L/min x m2), cardiac index at 50 watt (5.5 vs 4.5 vs 5.2 L/min x m2), stroke work at rest (51 vs 38 vs 42 pondmeter [PM]), stroke work at 50 watt (66 vs 48 vs 51 PM), pulmonary wedge pressure at rest (7 vs 13 vs 8 mm Hg) and pulmonary wedge pressure at 50 watt (14 vs 24 vs 18 mm Hg). CONCLUSION: It is concluded that electromechanical synchronization of the atria was of long-term benefit in heart transplant recipients with recipient sinus rhythm and donor sinus node disease.
Abstract: BACKGROUND: Transmyocardial laser revascularization is a new therapeutic option for end-stage coronary artery disease if no other cardiological or cardiosurgical intervention is possible. Data are few on how patients fare after more than 1 year follow-up. METHODS AND RESULTS: From a total of 157 patients who were suggested for transmyocardial laser therapy in the years 1995-1997, 126 were judged to have non-revascularizable coronary artery disease (mean age 61.9 +/- 14 years, 80% men, mean left ventricular ejection fraction 46.2 +/- 17.1%). Sixty-six patients had a good clinical response to intensification of the antianginal therapy and were therefore treated further medically. In 60 patients with refractory angina, sole transmyocardial laser revascularization without cardiopulmonary bypass or additional grafts was performed. The transmyocardial laser revascularization group was 32% female; 78.3% patients had had bypass operations; the mean left ventricular ejection fraction was 53.6 +/- 15%. Eighty five percent of the transmyocardial laser revascularization patients had demonstrable ischaemic regions, as visualized by dipyridamol-MIBI scintigraphy. The percentage of patients with some hibernating myocardium in positron emission tomography studies was 70%. Good early relief of angina symptoms was experienced by patients who had undergone laser treatment. After 3 months the Canadian Cardiovascular Society class fell from 3.31 +/- 0.51 to 1.84 +/- 0.77 in 49 patients (P < 0.0001), but increased in the total group to 2.02 +/- 0.92 after 6 months (n = 47), to 2.26 +/- 0.99 after 1 year (n = 42), to 2.47 +/- 1.11 after 2 years (n = 38) and to 2.58 +/- 0.9 after 3 years (n = 19). MIBI/positron emission tomography data at rest and after 6 months was worse in patients in whom pre- and postoperative studies were complete (n = 22). The peri-operative mortality was 12% (n = 7: peri-operative myocardial infarction, low output syndrome, arrhythmia). Mortality after 1 and 3 years was 23% and 30%, respectively. The risk of transmyocardial laser revascularization was significantly elevated in patients with left ventricular ejection fraction < 40%. Late deaths (n = 9) were due to sudden arrhythmias or pump failure. There was a high rate of cardiac events and reinterventions in the transmyocardial laser revascularization group, including percutaneous transluminal coronary angioplasty in newly developed lesions (n = 7), valve replacement (n = 2), need for intermittent urokinase therapy (n = 5) and heart transplantation (n = 2). CONCLUSION: Fifty percent of patients with non-revascularizable coronary artery disease submitted for transmyocardial laser revascularization can be stabilized medically. Transmyocardial laser revascularization led to a rapid early relief of symptoms, but with a trend towards worsening over time and showed a high peri-operative risk (> 10%) dependent on the pre-operative ejection fraction. Our data were in contrast to other published reports on the more beneficial effects of transmyocardial laser revascularization and should lead to further investigation of this experimental method. Transmyocardial laser revascularization should only be performed after failure of maximal anti-anginal therapy, and should be avoided when the left ventricular ejection fraction is < 40%.
Abstract: BACKGROUND AND OBJECTIVE: The medical management of heart failure improved greatly during the last decade. Heart transplantation (HTx) as surgical alternative is an established measure but operation numbers stagnated due to the lack of donor organs and still the 1 year mortality is about 20%. Rising numbers of new registrations led to long waiting lists with a high mortality rate. Solutions are intensified therapeutic concepts and improvements in organ allocation. This study was done to show if a combined intensified medical management and a regional donor allocation system may improve outcome in heart transplant candidates. PATIENTS AND METHODS: A cohort of 396 elective candidates for heart transplantation from the years 1984-1997 without contraindications and at least in NYHA stage III at entry were investigated for total mortality, modes of death and the probability of heart transplantation. Patients were divided in two groups (group A: submitted from 1984-1994, n = 256, group B: 1995-1998, n = 150). RESULTS: The groups were comparable in clinical and hemodynamic baseline characteristics. Patients of group B had a better long-term prognosis after 2 years (87% versus 73.5%, p = 0.009) and had a significantly lower rate of heart transplantation (HTx rate in group A and B after 2 years: 35% and 15%, p = 0.002). Only two patients died due to heart failure in the years 1995-1998 compared to 20 heart failure death from 1984-1994. The waiting time for a donor heart fell from 81.8 +/- 80 days in group A to 22.1 +/- 21 days in group B. The main problem is the unchanged sudden death rate in patients with stable hemodynamics prior to the event. CONCLUSIONS: A combination of tailored medical therapy for heart failure plus regionalization of donor heart allocation with short waiting time seems to be the best way to treat patients with end-stage heart failure. A specialized cardiomyopathy program is necessary for such an approach. Sudden death in heart transplant candidates has to be studied more intensively.
Abstract: OBJECTIVES: Primary prevention trials of antihypertensive therapy have shown conflicting results on coronary events. Potential interference of antihypertensive agents with cellular lipid metabolism may alter the atherosclerotic risk of individuals. DESIGN AND METHODS: The effects of the calcium antagonist's verapamil, diltiazem, and nifedipine and of the beta-blockers propranolol and metoprolol on low density lipoprotein (LDL) receptor activity, cholesterol esterification rate, oleate incorporation in triglycerides and sterol synthesis were studied in freshly isolated human leukocytes and HEP G2 cells. RESULTS: Up to a concentration of 3-10 mumol/L, verapamil, propranolol, and metoprolol led to an increased cellular content of 125I-LDL by an inhibition of degradation. In mononuclear cells verapamil stimulated accumulation and degradation. No effect on binding was observed. Diltiazem was only stimulatory on 125I-LDL processing in leukocytes. Beta blockers and verapamil significantly reduced the LDL mediated 14C-oleate incorporation in cholesterol esters. In the presence of 25-hydroxycholesterol the esterification was not diminished, which suggests that cholesterolacyltransferase (ACAT) was not affected per se. Whereas all the agents induced the synthesis of lanosterol, metoprolol inhibited cholesterol synthesis. None of the agents had a significant influence on 14C-oleate incorporation in triglycerides, suggesting a specific influence on cholesterol metabolism. CONCLUSIONS: Antihypertensive drugs affect the cholesterol metabolism on a cellular level. Mechanisms are an interference with degradation of LDL and consequent alterations of cholesterol esterification. Using leukocytes as peripheral cells and HEP G2 as a model of human liver, these results may have importance when antihypertensive long-term therapy is conducted for primary or secondary prevention of atherosclerotic complications.
Abstract: OBJECTIVE: Risk factors for the development of vasculopathy and malignancies as the most important causes of morbidity and mortality after heart transplantation are not well defined. METHODS: Univariate and multivariate Cox regression analysis of the data derived from our 84 survivors of more than 3 months after orthotopic heart transplantation between 1984 and 1996. Measurement of carbonmonoxide-hemoglobin blood levels with an ABL 520 analyzer. RESULTS: Recipient or donor age, the mode of immunosuppression, total-, LDL- and HDL-cholesterol, the HDL/LDL-ratio, triglycerides, hypertension, diabetes mellitus, CMV status and rejection episodes had no independent influence on total mortality or the occurrence of graft vasculopathy or cancer. By means of an intensive questionnaire (in case of deceased patients, by their relatives) and measurement of CO-Hb blood levels we detected a high rate of patients who smoked after transplantation (22/84 = 26%). Four patients confessed smoking after undergoing the blood test. Non-smokers were defined as denying it in the questionnaire and having CO-Mb levels < 2.5% in repeated measurements. All but one were smokers before heart transplantation. Mean consumption was 11 cigarettes per day. Five and 10 years survival was significantly reduced in smokers vs. non-smokers (37 vs. 80% and 10 vs. 74%, respectively, P < 0.0001). Survival curves diverged dramatically after 4 years of observation. Smokers had a higher prevalence of transplant vasculopathy as revealed by coronary angiography and/or autopsy (10/22 smokers vs. 2/62 non-smokers, P < 0.00001) and a higher rate of malignancies (7/22 smokers developed cancer, as compared to 4 cancers in 62 non-smokers, P = 0.0001). The primary site of cancer was the lung in 5/6 smoking and lymphoma in all non-smoking cancer patients. CONCLUSIONS: Our data show that the prevalence of smoking after heart transplantation may be relatively high, especially in former smokers. Repeated measurements of CO-Hb could be helpful in its detection. Despite a relatively low cigarette count, smoking is a major risk factor of morbidity and mortality after heart transplantation (HTx). Approximately 4 years of exposure time is needed to uncover its negative influence. These findings should lead to aggressive smoking screening and weaning programs in every HTx center.
Abstract: OBJECTIVES: LDL receptors of leukocytes play a key role in lipoprotein uptake, immunoregulation and the pathogenesis of atherosclerosis. Numerous studies with different methods of low reliability yielded conflicting results of its regulation in leukocyte subtypes. DESIGN AND METHODS: LDL receptors of human leukocytes were measured with use of the monoclonal antibody C-7. Specific C-7 binding was detected by FACS analysis using phycoerythrin-anti-mouse-IgG. Parallel incubations with FITC-labelled anti-LEU 4 (CD 3), anti-LEU 12 (CD 19) and anti-MY 4 (CD 14) antibodies were used to distinguish C-7 binding of specific cell types (T-, B-lymphocytes and monocytes). RESULTS: In contrast to monocytes, T and B-lymphocytes freshly isolated from healthy blood donors had no detectable binding capacity for C-7. After 24 and 48 h incubation of cells in a lipid-free medium, lymphocytes acquired some C-7 binding, albeit still much less than monocytes. Incubation with insulin for 24 h in a concentration of 0.5 microgram/mL led to an increase in C-7 binding for monocytes (up to 180%). Saturation experiments with the ligand suggests an increase in the number of receptors. In contrast the same insulin concentration inhibited C-7 binding of B- and T-lymphocytes by 35%. CONCLUSIONS: FACS analysis using monoclonal antibodies seems to be a feasible method for the investigation of lipid metabolism in leukocytes. The LDL receptor expression and its regulation by insulin differs in circulating monocytes and lymphocytes.
Abstract: Transmyocardial laser revascularization (TMR) is a new therapeutic principle for patients with coronary artery disease and no possibility of conventional revascularization with CABG or PTCA. The clinical value of the method is not known. Therefore we investigated all 46 patients treated with sole TMR in our center using clinical investigation, LV and coronary angiography, right heart catheterization, MIBI perfusion imaging and myocardial FDG-PET pre- and 6 months post TMR. 117 patients judged not suitable for conventional revascularization procedures were submitted for TMR. The indication for the procedure was reevaluated in every case. 52 patients (mean EF 41 +/- 16%) could be further treated by intensified anti-anginal medication, seven patients received bypass grafts, four patients had PTCA, three patients were listed for heart transplantation, and five patients had a combined CABG plus TMR. Only 46 (38% of the submitted patients, mean EF 55 +/- 15%) were accepted for sole TMR. CCS class of these patients was 3.3 +/- 0.4, mean age was 63.6 +/- 7.3 years, 70% were males. The postoperative mortality within 30 days was 5/46 (10.8%); 9/46 patients (19.5%) suffered from perioperative myocardial infarction. Other complications were ventricular fibrillation in two cases on the second postoperative day and a rupture of the spleen on the 14th postoperative day. 8/46 patients (17%) had wound infections. Survivors showed an improvement in their CCS class (1.9, 2.1, 1.9 after 3, 6 and 12 months, respectively, mean observation time 0.61 +/- 0.4 years). These patients were able to perform bicycle stress tests significantly longer (98 s +/- 9 pre versus 120 +/- 13 s post TMR, p = 0.01). Angiographic EF fell from 57.8% +/- 15% to 52.6% +/- 19% (p = 0.02) and the number of hypokinetic chords rose from 23.6 +/- 20.9% to 30.6 +/- 24.1% per patient (p = 0.008), predominantly in the inferior wall. Nuclear studies showed reduced myocardial perfusion and vitality after TMR. Four patients in the TMR group had reintervention (PTCA) because of progression of coronary sclerosis of native vessels. One patient had mitral valve replacement due to severe regurgitation. Kaplan-Meier analysis showed no significant difference in survival between the TMR and the medical group when stratified according to initial ejection fraction. Sudden death and congestive heart failure are the most important causes of mortality. Our data show that TMR improves symptoms and exercise performance of otherwise not treatable patients with diffuse coronary artery disease. Due to a lack of an improvement of cardiac perfusion, function or prognosis TMR should be used only in highly selected cases when conventional methods fail to improve patients symptoms.
Abstract: We describe unexpected episodes of paced tachycardia in two patients with rate-responsive pacemakers during anaesthesia. Five months after a heart transplant and implantation of a pacemaker a 43-year-old patient suffered cardiac tamponade as a result of chronic pericarditis. The second case involved embolic occlusion of the femoral artery in a 33-year-old female patient previously operated on for tricuspid valve replacement and implantation of a pacemaker. In both cases induction of anaesthesia was performed with fentanyl, etomidate and vecuronium. Following intubation and mechanical ventilation, the heart rates (HR) of the two patients increased to 140 and 130 min-1 respectively. This was interpreted as a sign of inadequate anaesthesia, and therefore additional doses of fentanyl and etomidate were given, with no effect on the tachycardia. After exclusion of other possible reasons for this complication such as hypokalaemia, hypercapnia, hypoxaemia or allergic reactions, unexpected functioning of the rate-responsive pacemakers due to thoracic impedance changes was assumed. Minute ventilation was reduced, lowering paced HR in 3-5 min. CONCLUSIONS: These case reports suggest that anaesthetic management affects the action of rate-responsive pacemakers, causing haemodynamic complications, and inadequate interventions by the anaesthesiologist. Thus, it is necessary for anaesthesiologists to make a preoperative evaluation of the underlying medical disease and the type of pacemaker in order to adjust anaesthetic management accordingly and to understand the haemodynamic responses that may occur during the perioperative period. Preoperative programming to exclude the rate-responsive function is advised.
Abstract: It is currently under debate whether the low serum cholesterol levels that are frequently observed in cancer patients represent a risk factor for/or, rather, are a consequence of the tumour. We postulate that malignant tumours are directly involved in an increased catabolism of cholesterol-rich low-density lipoprotein (LDL) particles. In a prospective study of 25 patients with colorectal carcinoma, we measured intraindividual shifts in serum cholesterol levels after surgery, and the expression of LDL-receptor mRNA in surgically removed specimens. A significant rise in plasma cholesterol levels was observed in patients 3 and 12 months after curative surgery, but not after non-curative surgery. In human colon carcinoma tissues LDL receptor mRNA expression, as determined by competitive reverse-transcriptase-polymerase-chain reaction, was found to be significantly increased when compared to tissues from the tumour-free margin (median values, 1.2 x 10(6) vs. 2.0 x 10(5) molecules/micrograms total cellular RNA, respectively, n = 17). The extent of LDL-receptor mRNA expression positively correlated to the percentage rise of plasma cholesterol levels 3 months (n = 7, r = 0.8763) and 12 months (n = 6, r = 0.9181) after curative surgery. This finding provides in vivo evidence that the tumour tissue itself contributes to decreased plasma cholesterol levels in patients suffering from colorectal carcinomas. It supports the hypothesis that low cholesterol levels in cancer patients are a consequence, and not the cause, of the malignancy.
Abstract: Twenty-two patients with acute myeloblastic leukaemia (AML) were studied to investigate disease-associated changes in lipid metabolism. Lipoprotein (a) [Lp(a)] levels were found to be elevated at the time of diagnosis (median 23 mg/dl; 41% of patient group had levels greater than 25 mg/dl) and diminished after successful chemotherapeutic treatment in 9 of 10 cases, with a maximum decrease from 56 to 10 mg/dl. In contrast, reduced levels of total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL) (medians 137, 87 and 20 mg/dl, respectively) were observed at the time of diagnosis. Cholesterol and HDL levels increased in all 10 and LDL in 9 cases in which complete remission was achieved. These data suggest that the catabolism of LDL-cholesterol might be even more enhanced than assumed to date. Furthermore, it indicates that the Lp(a) level in acute myeloblastic leukaemia is influenced either directly or indirectly by the leukaemic blasts.
Abstract: A 41-year-old man with type II diabetes for the past five years had for three weeks been suffering from high fever (up to 40 degrees), feeling of pressure in the upper abdomen, loss of weight, lack of appetite and increasing weakness. Ultrasound examination as an out-patient was suspicious of diffuse liver metastases from an unknown primary tumour. Ultrasonography and computed tomography after hospitalization suggested multiple liver abscesses. Fine-needle biopsy grew Yersinia enterocolitica. In addition, there was evidence of an asymptomatic intestinal Yersinia infection without septicaemia. After intravenous treatment with three times daily 5 g mezlocillin and three times daily 80 mg tobramycin the fever at first subsided, but the liver abscesses remained unchanged. When fever recurred a week later, cefotaxim, three times daily 2 g, was started. This led to complete regression of the abscesses within three weeks, and the patient has been free of symptoms since.
Abstract: There is controversy whether various classes of antihypertensive drugs can reduce significantly cardiovascular morbidity and mortality in primary prevention. A failure to show this in many studies was attributed, at least in part, to deleterious effects of these drugs on lipid metabolism. Especially adrenergic antihypertensives cause marked effects on lipoprotein levels in plasma. A review of the literature revealed that beta-blockers increase triglycerides and VLDL (very low density lipoprotein)-cholesterol and may lower plasma HDL (high density lipoprotein) levels. In contrast alpha 1-adrenergic inhibitors like prazosin, doxazosin and terazosin lower triglycerides, total cholesterol, LDL (low density lipoprotein)- and VLDL-cholesterol and increase plasma HDL levels. The mechanisms by which alpha- and beta-blockers may produce the observed effects on plasma lipids and lipoproteins are not well understood. It has been shown in our laboratory that the activity of the LDL receptor of peripheral cells, a major determinant of cholesterol levels in plasma, is regulated by catecholamines via alpha 2- and beta 2-adrenergic receptors. Accordingly, blockade of these adrenoceptors with alpha- and beta-adrenergic antagonists can reverse the catecholamine effect. In addition these agents may affect lipoprotein lipase, lecithin cholesteryl acyltransferase and cholesterol ester hydrolase. These data may explain, at least in part, the plasma effects. However, long-term studies are needed to clarify the clinical value of antihypertensives with different metabolic profiles.
Abstract: The mechanisms by which insulin and catecholamines affect low-density lipoprotein (LDL)-receptor activity were studied in freshly isolated human mononuclear leukocytes. Incubation of cells for up to 24 h in a lipid-free medium resulted in an increase in the specific binding, accumulation, and degradation of 125I-labeled LDL. Insulin stimulated the ability of the cells to bind, accumulate, and degrade the lipoprotein with high affinity, which may be caused by an increase in the LDL-receptor number without altering binding affinity. (-)-Epinephrine inhibited the specific binding, accumulation, and degradation of 125I-LDL. This effect appears to be mediated by a decrease in the number of LDL receptors and not by a change in the binding affinity. (-)-Norepinephrine, the unspecific beta-adrenergic agonist (-)-isoproterenol, and the beta 2-specific agonist terbutaline mimicked the effect of epinephrine on LDL-receptor activity. Catecholamines and beta-adrenergic agonists yielded sigmoidal log-concentration effect curves. The action of epinephrine was attenuated by the beta-antagonist (dl)-propranolol. These results demonstrate that insulin stimulates and catecholamines suppress the specific binding, accumulation, and degradation of 125I-LDL in human mononuclear leukocytes. The catecholamine action appears to be mediated by beta 2-adrenergic receptors. A suppression of LDL-receptor activity resulting from deficiency of insulin and elevated plasma catecholamine concentrations in uncontrolled insulin-dependent diabetic patients may contribute to the increased levels of LDL cholesterol observed in these patients.
Abstract: There is good epidemiologic evidence that hypertension is associated with a high risk of cardiovascular disease. However, primary intervention trials have failed to demonstrate that a reduction in blood pressure in hypertensive patients reduces morbidity and mortality from cardiac events. Since various antihypertensive drugs adversely affect lipoprotein metabolism, these drugs may increase associated coronary risk and offset the beneficial effects of lowering blood pressure. This article reviews the effects of various antihypertensive drugs on plasma lipids, lipoproteins, and apolipoproteins. They can be summarized as follows: thiazide-type diuretics cause a marked elevation of plasma triglycerides and very low-density lipoprotein (VLDL) and minor increases in total cholesterol and low-density lipoprotein (LDL), but have little effects on high-density lipoprotein (HDL). The nonselective beta-blockers do not significantly affect total cholesterol and LDL, but increase total triglycerides and VLDL and decrease HDL. The changes in plasma lipids and lipoproteins caused by cardioselective beta-blockers and beta-blockers with intrinsic sympathomimetic activity are qualitatively similar but less pronounced. Calcium antagonists and angiotensin-converting enzyme inhibitors appear to have no significant effects on plasma lipids. alpha 1-Inhibitors reduce total triglycerides, total cholesterol, VLDL, and LDL and increase HDL. The possible mechanisms by which antihypertensive drugs affect cellular lipid metabolism (e.g., LDL receptor, lipid synthesis, lipoprotein lipase, lecithin cholesteryl acyltransferase, acylcholesteryl acyltransferase, and cholesteryl ester hydrolase) are described. The clinical significance of changes in blood lipids and cellular lipid metabolism caused by antihypertensive drugs is not yet totally clear. Nevertheless, before antihypertensive drug treatment is initiated, blood lipid levels should be measured to identify preexisting hyperlipidemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: The effects of prostaglandin (PG) E1, PGE2, the stable prostacyclin analogue Iloprost, and PGF2 alpha on low density lipoprotein (LDL) receptor activity and cholesterol synthesis were investigated in freshly isolated human mononuclear leukocytes. Incubation of cells for up to 45 hr in a lipid-free medium resulted in an increase in the rate of cholesterol synthesis from [14C]acetate and the high affinity accumulation and degradation of 125I-labeled LDL. Addition of PGE1 in increasing concentrations to the incubation medium inhibited cholesterol synthesis and the specific accumulation and degradation of 125I-labeled LDL; at a concentration of 10 microM, the inhibitions were 61%, 70%, and 67%, respectively, after an incubation of 20 hr. The effects of PGE2 and Iloprost were similar. The action of the prostaglandins on LDL receptor activity appeared to be mediated by a decrease in the number of LDL receptors and not by a change in the binding affinity. The prostaglandins yielded sigmoidal log concentration-effect curves. In contrast, PGF2 alpha had no influence on cholesterol synthesis or LDL receptor activity up to a concentration of 10 microM. PGE1, PGE2, and Iloprost, but not PGF2 alpha, led to an increase in the concentration of intracellular cyclic AMP. Dibutyryl cyclic AMP mimicked the effects of the E-prostaglandins and Iloprost on the LDL receptor activity. The results suggest that PGE1, PGE2, and prostacyclin affect LDL receptor activity and cholesterol synthesis and, therefore, may play a role in the regulation of cholesterol homeostasis and in the development of atherosclerosis.
Abstract: Calcium antagonists and antihypertensive alpha-adrenergic and beta-adrenergic drugs may cause changes in plasma lipoprotein levels. Different mechanisms by which these antihypertensive agents effect cellular lipid metabolism have been proposed. The activity of lipoprotein lipase that determines the catabolism of very low density lipoproteins (VLDL) is decreased by the beta-blocker propranolol and increased by alpha 1-antagonists. The plasma cholesterol or low density lipoprotein (LDL) level is inversely associated with the number of LDL receptors. Catecholamines suppress the LDL receptor activity, thus leading to an increase in plasma cholesterol concentration. The calcium antagonist verapamil and the beta-blocker propranolol may increase LDL receptor activity either per se or by its antagonizing effect on the catecholamine action. The metabolism of high density lipoproteins (HDL) may be affected directly by catecholamines, which might increase HDL binding activity, thereby enhancing efflux of cholesterol from cells. Catecholamines inhibit cholesterol biosynthesis in extrahepatic cells. The effects are mediated by alpha 2- and beta 2-adrenergic receptors. Accordingly, the alpha 2-agonists clonidine and alpha-methyldopa mimicked and propranolol opposed the catecholamine action. In contrast, the alpha 1 antagonists indoramin, prazosin, and urapidil had no effect on cholesterol synthesis. The results provide evidence that calcium antagonists and various antihypertensive drugs, depending upon their action on beta- or alpha-adrenergic receptors, affect lipid metabolism differently. The metabolic effect may play a role in atherogenesis and may be of clinical importance when antihypertensive treatment is considered.
Abstract: Es soll eine Ãbersicht zu pathophysiologischen Grundlagen und klinischen Erfolgen einer Bewegungsbehandlung bei Herzinsuffizienz gegeben werden.
Abstract: Due to pioneering work (2) and recently published randomized studies (1,3) biventricular stimulation (BVS) is now an accepted method for therapy of heart failure in the presence of intraventricular conduction delay. However most studies with BVS were done in patients with sinus rhythm and it was speculated whether efficacy of the method is reduced when atrial fibrillation (AF) was present (4). Furthermore it is unknown whether BVS has beneficial efffects in terms of stabilization of or conversion to sinus rhythm.
Abstract: Due to pioneering work (3) and recently published randomized studies (1,4) biventricular pacing is now an accepted method for therapy of heart failure in the presence of intraventricular conduction delay. Up to now it is a matter of debate whether patients with heart failure, conventional pacemakers and permanent right ventricular stimulation will profit from upgrade to biventricular pacing. Hearts of patients with artificial pacemaker stimulation showed paradoxical septal motion and apical perfusion defects (5). We could show that conventional DDD pacing is indeed deleterious in heart failure patients (7). Theoretically biventricular pacing will correct this artificial form of intraventricular conduction delay and the sequela of uncoordinated ventricular contraction.
Abstract: Pacemaker infection or some lead dysfunctions are an indication for removal of all foreign material (2). The use of laser energy is a new method for the extraction of fixed leads being in place for a long time (1,3,4). We report our results using the Spectranetics system using LLD locking stylets, laser sheaths and an excimer laser as energy source in 51 patients and 104 leads.
Abstract: Due to pioneering work (2) and recently published randomized studies (1,3) biventricular pacing is now an accepted method for therapy of heart failure in the presence of intraventricular conduction delay. However for a widespread application of this method coronary sinus (CS) lead performance is of crucial importance. In contrast to the right ventricle, CS lead implantation is a totally different and complex procedure due to individual variations in venous anatomy (5). It was therefore not surprising that the first approach for left ventricular pacing was epicardial lead placing via thoracotomy. Only after the the development of special CS leads and introducer systems in the late 90s this invasive and potentially dangerous procedure has been replaced by transvenous techniques (4). However there still is an evolution of lead and introducer design including placing utilities such as wires. The shape of the lead was also the topic of intense development leading to angulated or curved lead bodies (6). In this work we want to compare our results of straight- and preshaped coronary sinus leads both using the over-the wire technique in mid-term follow-up.
Abstract: Introduction: Telemonitoring of vital parameters such as weight and blood pressure reduces mortality and may shorten duration of re-hospitalization in heart failure patients. Data recorded by implantable CRT(-D) devices could be used for the same purpose. CRT devices with Home Monitoring (HM) capability integrate a Heart Failure Monitor (HFM) to screen the clinical status of heart failure patients continuously. The HFM consists of a comprehensive set of clinical parameters shown to predict cardiovascular hospitalizations (CVH). Using advanced biometric approaches, an optimal multi-parameter predictor has been developed. We report on the predictive power of the 1st HFM generation, which we evaluated using the Home CARE Phase 0 and preliminary Home CARE study data.
Methods: The analysis included 339 patients treated with Kronos LV-T (ICD-CRT) devices (78% male, 66 ± 10 years, 57% ischemic etiology, QRS duration 163 ± 39 ms, NYHA class II (13%), III (77%) and IV (8%)). Daily transmitted HFM data were stored in a central HM service center. In order to develop a predictive algorithm, we investigated HM based time series comprising CVH or no CVH (control) in a retrospective manner, within a time window of 40 days prior to a CVH event. We analysed the predictive performance of the combination of daily mean heart rate, mean heart rate at rest, patient activity, number of ventricular extrasystoles per hour and lead impedances.
Results: Within a follow up of 11 ± 4 months, 28 CVHs were reported (20 due to worsening of heart failure, 7 due to rhythm disturbance, 1 due to acute coronary syndrome). Event and control data differed on a level of significance of p<0.001 (Kolmogorov for unpaired nonparametric testing). Retrospective discrimination of event data against controls resulted in a sensitivity of 75% and a specificity of 97%. Using Monte-Carlo methods under the assumption of normal distribution, a-posteriori uncertainties of 9% and 3% (standard deviation of means) were derived.
Conclusions: Prediction of CVH by the 1st generation of HFM (multi-parameter advanced biometric analysis) is feasible. By stepwise upgrading of the HFM with additional parameters, like heart rate variability, we expect further increase of the predictive performance, which we term add-on strategy for HFM evolution. The verification of the results on a wider data basis and a prospective evaluation of the predictive performance are warranted.
Abstract: Einleitung: Herzinsuffiziente Patienten (Pt) werden zunehmend mit Defibrillatoren und/oder Resynchronisationssystemen (CRT) versorgt. Eine internetbasierte kontinuierliche Datenübertragung von Warnmeldungen per Mobilfunk bei Erreichung bestimmter Grenzwerte bietet sich zur Ãberwachung dieser Pt an.
Methode: Wir analysierten retrospektiv die Daten von 105 Pt, welche in den Jahren 2004-2008 n=118 Implantate mit dem Mobilfunk- und Internetbasierten âHomemonitoringâ-System der Fa. Biotronik erhalten haben (LUMAX HFT n=55, KRONOS LVT n=27, LUMOS VRT n=14, STRATOS LVT n=12, AIRBAG n=9, BELOS DRT n=1). Die Warnmeldungen wurden mittels intrakardialer Elektrogramme (sofern verfügbar) oder klinischen Daten validiert und die Konsequenzen an Hand der Kontrollberichte der Defi- und Schrittmacherambulanz überprüft.
Ergebnisse: Es wurden insgesamt 179 Patientenjahre analysiert (Mittelwert pro Pt 1,52 ± 1 Jahr). Es gingen 1359 Warnmeldungen bei 62% der Pt ein (im Mittel 11/Pt). Nach Häufigkeit wurde gemeldet: niedrige CRT-Rate: 35 Pt, Kammerflimmern: 25 Pt (6x unbemerkt), Kammertachykardie: 10 Pt (7x unbemerkt), Vorhofflimmern: 14 Pt, Batterieermüdung (ERI): 8 Pt, Impedanzabweichungen: 6 Patienten. Konsequenzen aus den Warnmeldungen waren: 8x Aggregatwechsel bei ERI, 5x ICD-Elektrodenwechsel bei Störsignalen oder Reizschwellenanstieg, 3x Koronarsinuselektrodenrevision bei Dislokation, 3x Umprogrammierung bei T-Wellenoversensing, 14x Steigerung von Ã-Blockern und/oder Amiodarongabe. Bei 23 Pt wurde die Ãberwachung entweder bei Rücknahme der Einverständnis (n=11) oder technischen Schwierigkeiten abgebrochen (n=12).
Schlussfolgerung: Eine internetbasierte Fernüberwachung von herzinsuffizienten Patienten mit implantierten Stimulationssystemen eignet sich zur (zumindest früheren) Erkennung von Komplikationen. Bei einem signifikanten Anteil der Patienten wird die Fernüberwachung jedoch aus unterschiedlichen Gründen abgebrochen.
Abstract: Einleitung: Die cardiale Resynchronisationstherapie (CRT) ist inzwischen Standardbehandlung bei entsprechender Indikation. Leider verbleiben ca. 30% der Patienten trotz CRT im Status eines Non-Responders (NR). Die âCardiac Contractility Modulationâ (CCM) bietet sich hier als Reservemöglichkeit an. Der klinische Verlauf und die Prognose von CRT-NR unter additiver CCM-Therapie und Selektionskriterien für diese kostenintensive und invasive Therapieform sind bislang unbekannt.
Methoden: Im Zeitraum 09/2007-11/2008 wurde eine zusätzliche CCM-Implantation (OPTIMIZER III, Impulse Dynamics, Orangeburg, NY, USA) bei 20 CRT-NR Patienten (mittleres Alter 66 ± 9 Jahre, mittlere LVEF 25 ± 7 %) der NYHA Klassen III (n=12, peak VO2 10,9 ml/min*kg) oder IV (n=8, peak VO2 5,4 ml/min*kg) durchgeführt. Alle Patienten hatten bereits einen CRT-Defibrillator seit im Mittel 1,9 ± 0,8 Jahren implantiert. Alle Patienten zeigten intraoperativ einen Anstieg der invasiv gemessenen LV dp/dt von im Mittel 14 ± 5% (15% NYHA IV versus 13% NYHA III, p=n.s.). Die Patienten wurden prospektiv nachuntersucht.
Resultate: Die Prognose der CRT-NR im NYHA IV Stadium eingangs war signifikant schlechter verglichen zu CRT-NR der NYHA-Klasse III (0% versus 80% aktuarische 1-Jahresüberlebensrate, p=0,01). NYHA III Patienten zeigten ein BNP-Abfall nach 3 Monaten unter CCM (-295 pg/ml), während NYHA IV CRT-NR unter CCM weiter anstiegen (+830 pg/ml, p<0.01 versus NYHA III).
Schlussfolgerung: Eine additive CCM sollte bei CRT-NR der Klasse IV nicht mehr durchgeführt werden. NYHA III CRT-NR könnten von der neuen Behandlungsform profitieren, wobei randomisierte Studien fehlen. Als Selektionskriterium bietet sich die Messung der maximalen Sauerstoffaufnahme an (zu fordern >10 ml/min*kg).
Abstract: Introduction: Management of heart failure patients via telemonitoring reduces mortality, but frequent cardiovascular hospitalizations (CVH) remain a problem. Continous monitoring of the patient's clinical status is enabled by CRT(-D) devices with Home Monitoring (HM) capability. A set of parameters shown to predict cardiovascular hospitalizations is integrated in a Heart Failure Monitor (HFM). We report on the predictive power of the 1st HFM generation, which was evaluated using multi-parameter advanced biometric analysis based on the Home CARE Phase 0 and preliminary Home CARE study data.
Methods: The retrospective analysis included 339 patients implanted with Kronos LV-T (CRT-D) devices and followed for 11±4 months (78% male, 66±10 years, 57% ischemic etiology, QRS duration 163±39 ms, NYHA class II (13%), III (77%) and IV (8%)). In order to develop a predictive algorithm, we compared HM time series within a time window of 40 days prior to a CVH with event-free control data. We analysed the predictive performance of the combination of daily mean heart rate, mean heart rate at rest, patient activity, number of ventricular extrasystoles per hour and lead impedances.
Results: Preliminary analyis was performed including 35 CVHs (27 due to worsening of heart failure, 7 due to rhythm disturbance, 1 due to acute coronary syndrome). Event and control data differed on a level of significance of p<0.001 (Kolmogorov for unpaired nonparametric testing). Retrospective discrimination of event data against controls resulted in a sensitivity of 80% and a specificity of 97%. Using Monte-Carlo methods under the assumption of normal distribution, a-posteriori uncertainties of 9% and 3% (standard deviation of means) were derived.
Conclusions: Prediction of CVH by multi-parameter HFM using advanced biometric analysis is feasible. By stepwise upgrading of the HFM with additional parameters, like heart rate variability, we expect further increase of the predictive performance. The verification of the results on a wider data basis and a prospective evaluation of the predictive performance are warranted.
Abstract: Abstract
Dieser Fallbericht beschreibt die Beendigung eines CRT-Nonresponderstatus durch Wechsel von epikardialer zu transvenöser LV-Stimulation.
Main text:
We report on a 55-year-old patient with dilated cardiomyopathy. His left ventricular ejection fraction (LVEF) was 18% at first presentation. He was in NYHA stage III in spite of optimized medical therapy. Heart transplantation was considered as an option, but the patient also showed a complete left bundle brunch block. Therefore he received a CRT defibrillator system in June 2006. Two dislocations of coronary sinus (CS) leads occurred and finally a surgical approach was chosen. An epicardial LV lead was placed via left lateral thoracotomy. As the patients condition did not improve (NYHA class III, BNP levels 3800 pg/ml. LVEF 15%) during the next months he was admitted for further evaluation. Pacemaker check revealed normal sensing and pacing thresholds, and his ECG appeared to show biventricular pacing with a reduction in QRS width by 30 ms to 150 ms. Tissue Doppler imaging revealed the presence of asynchrony despite formal correct biventricular pacing.
A review of the lateral x-ray revealed that the epicardial lead was placed antero-laterally close to the right ventricular lead (figure). The distance between the RV and the EPI lead equalled only about 25% of the total cardiac anterior posterior diameter. Therefore a forth revision was performed in February 2007 and a newly available active CS lead (model 4195, âStarfixâ, Medtronic Inc, Minneapolis, MN, U.S.A.) could be successfully placed in a stable posterolateral position now very distant to the RV (figure). Details of the implant procedure have been described elsewhere (2). The distance between the RV and the active fixation LV lead now equals more than 90% of the total cardiac anterior posterior diameter (figure). The patient immediately felt better and has since an uneventful course in NYHA class I for more than 1 year. His ejection fraction increased to 35% and BNP levels decreased to 278 pg/ml. No more asynchrony could be noted by tissue Doppler analysis. The patientâs activity log most impressively showed a fast increase after the lead revision (figure).
To our knowledge this is the first report of a patient in whom CRT NR status could be reversed by repositioning of LV leads. In this regard the importance of the transverse interlead distance was highlighted (3). Anterior-posterior chest x-rays should be critically reviewed in every CRT-NR patient, even in the presence of epicardial leads in context with existing CS angiograms in order to determine whether lead revision could reverse the patientâs NR status. In this regard several newly available leads and tools may be very helpful in difficult cases with lead problems or dislocations in prior interventions.
Abstract: Einsatz der âCardiac Contractility Modulationâ (CCM) bei Non-Respondern der Cardialen Resynchronisationstherapie (CRT)
Nägele H, Behrens S, Eisermann C
St. Adolfstift, Medizinische Klinik, Reinbek, Germany
Einleitung: Die cardiale Resynchronisationstherapie (CRT) ist inzwischen eine Standardbehandlung bei eingeschänkter Kammerfunktion und QRS-Verbreiterung. Leider verbleiben 20-30% der Patienten im Status eines Non-Responders (NR). Zusätzliche Behandlungsverfahren werden bei diesen Patienten dringend benötigt. Hier bietet sich die âCardiac Contractility Modulationâ (CCM) an. Dabei werden â vorhofgetriggert â nicht - erregende Impulse mit hoher Energie in der absoluten Refraktärperiode über zwei Schraubelelektroden am interventrikulären Septum appliziert. Darunter kommt es zu einer Steigerung der Druckanstiegsgeschwindigkeit (LV dp/dt).
Methoden: Im Zeitraum 09/2007-06/2008 wurde eine zusätzliche CCM-Implantation (OPTIMIZER III, Impulse Dynamics, Orangeburg, NY, USA) bei 16 CRT âNR Patienten (mittleres Alter 65 ± 9 Jahre, mittlere LVEF 25,8 ± 4,7 %) der NYHA Klassen III (n=11) oder IV (n=5) durchgeführt. Alle Patienten hatten bereits einen CRT-Defibrillator seit im Mittel 1,9 ± 0,8 Jahren implantiert. Akute Ãnderungen der LV dp/dt während CCM-Stimulation wurden über transfemoral plazierte 5F Millar Katheter gemessen. Die Patienten wurden prospektiv nachuntersucht.
Resultate: Bei allen 16 Patienten (teilweise erst nach mehrfachen Elektrodenumplazierungen) stieg die LV dp/dt unter CCM-Stimulation akut im Mittel von 557 ± 183 auf 632 ± 212 mmHg/sec. an (+12%, +Spannweite 6-28%, p<0.001). Wir beobachteten folgende Komplikationen und Ereignisse während des Nachsorgezeitraums von im Mittel 93 ± 48 Tagen (Spannweite 8-246): Intra-OP Kammerflattern (n=1), Vorhofelektrodendislokation (n=1), Koronarsinuselektroden- dislokation (n=1), schmerzhafte CCM-Stimulation mit Notwendigkeit der Elektrodenumplazierung (n=1), wahre Defibrillator Schocks (n=2), kardiale Dekompensation (n=3, 2x während niedriger CCM-Therapieabgabe), Vorhofflimmern (n=1), Pneumonie (n=2). Die NYHA Klasse verbesserte sich im Mittel von 3,4 auf 2,7 (p<0.01), und die LVEF von 27,3 ± 5 % auf 31,1 % (p<0.01). Alle Patienten konnten nach Hause entlassen werden, es gab bislang keinen Todesfall. Es traten keine Interferenzen zwischen den implantierten CCM- und CRT-Defibrillatorsystemen auf, insbesonders gab es keine inadäquaten Schocks.
Schlussfolgerung: CCM kann eine sinnvolle additive Behandlungsform für CRT â Non-Responder darstellen, wenn alle anderen Behandlungsmöglichkeiten ausgeschöpft sind.
Abstract: Bis zu 10% der Einwohner westlicher Industrienationen leiden an Zuckerkrankheit (Diabetes mellitus). Die häufigste Form stellt der übergewichtige, ältere Zuckerkranke dar, bei dem sich die Erkrankung erst in der 2. Lebenshälfte manifestiert, während der klassische insulinbedürftige, schlanke, sogenannte âTyp 1â Diabetiker nur einen kleinen Prozentsatz davon ausmacht. Deshalb soll in diesem Artikel hauptsächlich auf den so genannten Typ 2 Diabetes eingegangen werden.
Durch die verfügbaren Behandlungsmethoden wie Insulin oder âZuckertablettenâ ist die Sterblichkeit an der Zuckerkrankheit selbst (z.B. im Zuckerkoma) selten geworden. Allerdings sind Zuckerkranke erheblich bedroht durch GefäÃkomplikationen (sogenannte âMakroâ- und âMikrovaskulopathieâ) wie Herzinfarkt, Schlaganfall, Nierenschäden, Augenhintergrundveränderungen (Retinopathie) und offene Beine. Das Infarktrisiko von Diabetikern gleicht dem von Nicht-Diabetikern mit Infarktanamnese. Die Sterblichkeit an einem solchen Ereignis ist für Diabetiker trotz Koronarintervention mittels Herzkatheter und leitliniengerechter Behandlung doppelt so hoch (RÃHNISCH 2007).
Diabetiker sind häufiger als die restliche Bevölkerung krank geschrieben, erwerbslos oder frühzeitig im Rentenverfahren. Dies belastet unsere Gesellschaft finanziell erheblich, für das Jahr 2002 wurden für die USA Ausgaben von 132 Milliarden US-Dollar für Schäden durch die Zuckerkrankheit angegeben. Es ist daher notwendig systematisch nach einer möglichen Zuckerkrankheit zu fahnden und diese zu charakterisieren, um so frühzeitig wie möglich eine Behandlung einzuleiten. Hierzu gibt es standardisierte Handlungsanweisungen (Leitlinien), wie sie z.B. zuletzt im Jahre 2006 aktualisiert wurden (NATHAN 2006). Vor allem muss, wie oben begründet, auf die diabetischen GefäÃschädigungen geachtet werden.
Abstract: Die Herzinsuffizienz, oder auch Herzschwäche genannt ist gekennzeichnet durch Unfähigkeit des Herzens die Gewebe ausreichend mit Sauerstoff in Ruhe oder bei Anstrengung zu versorgen. Dies führt zu Ruhebeschwerden oder einer eingeschränkten körperlichen Belastbarkeit. Von einer Herzinsuffizienz kann nur gesprochen werden wenn sich tatsächlich eine Funktionsstörung des Herzens nachweisen lässt (WHO-Definition). Es wird unterschieden zwischen einer Erkrankung des rechten Herzens (Rechtsherzinsuffizienz) oder des linken Herzens (Linksherzinsuffizienz). Häufig finden sich jedoch Mischbilder (biventrikuläre oder globale Herzinsuffizienz). Die Linksherzinsuffizienz führt über Stauung in der Lunge bis zum Wasseraustritt in die Lungenbläschen zu Luftnot, die Rechtsherzinsuffizienz ist dagegen gekennzeichnet durch Wassereinlagerung zunächst in den Beinen (Ãdeme) und später dann auch durch Stauung der inneren Organe mit LebervergröÃerung oder Bauchwasser (Aszites). Die Organstauung führt zu Appetitlosigkeit und verminderter Aufnahme von Nährstoffen. Ein wichtiges Problem ist die Muskelschwäche und Muskelabbau, der bei den schweren Formen auftreten kann. Verursacht ist dieser einmal durch eine durch Luftnot erzwungene Inaktivität, aber auch durch Energie- und Sauerstoffmangel im Muskel selbst. Das bedrohlichste Problem sind jedoch Herzrhythmusstörungen, die oft leider vom Patienten nicht, oder zu spät wahrgenommen werden und sogar zum plötzlichen Herztod führen können.
Abstract: Die Elektrotherapie des Herzens mit implantierbaren Geräten wie Schrittmacher, Defibrillatoren und/oder Monitoringsystemen (Ereignisrekorder) ist neben der invasiven KoronargefäÃbehandlung und der ablativen Behandlung von Herzrhythmusstörungen zu einer der Erfolgsgeschichten der modernen Kardiologie geworden. Es soll eine Ãbersicht zu diesem Thema gegeben werden, welche sowohl geschichtliche Aspekte, den heutigen Stand und Zukunftsausblicke beeinhaltet. Seit Erstimplantation eines Herzschrittmachers vor 50 Jahren entwickelt sie sich von einer rein lebenserhaltenden MaÃnahme zu einer immer differenzierteren Therapieform. Heute sind Lebensqualität, Leistungsfähigkeit und Langzeitprognose die wichtigsten Ziele. Um diese Anforderungen zu erreichen, sollen die Systeme einen weitgehend physiologischen (normalen) Zustand erhalten bzw. wieder herstellen.
Abstract: Schlafapnoe bei Herzinsuffizienz
Trotz der Fortschritte in der Behandlung der chronischen Herzinsuffizienz verursacht die Erkrankung noch häufig einschränkende Beschwerden, Einweisungen ins Krankenhaus und eine hohe Sterblichkeit. Weitere MaÃnahmen, die Symptome verringern, zu einer Zunahme der Lebensqualität führen als auch die Krankenhausaufnahmen und die Sterblichkeit vermindern, werden also dringend benötigt. Die Behandlung schlafbezogener Atmungsstörungen ist möglicherweise solch eine sinnvolle MaÃnahme.
Schlafbezogene Atmungsstörungen sind bei ungefähr 75% aller Patienten mit einer Herzinsuffizienz nachweisbar, wobei circa 50% relevante Atempausen aufweisen. Man unterscheidet zwei verschiedene Arten der gestörten Atmung: die obstruktive Schlafapnoe (OSA) und die zentrale Schlafapnoe (ZSA), die bei Vorliegen einer Herzinsuffizienz Cheyne-Stokes-Atmung (CSA) genannt wird. OSA wird bei 20-45% der HF-Patienten gefunden, während CSA bei 25-40% nachweisbar ist. Diese Erkenntnisse beziehen sich auch auf stabile Herzinsuffizienz-Patienten, die leitliniengerecht behandelt werden.
Während das klassische Symptom der obstruktiven Schlafapnoe der unerholsame Schlaf mit konsekutiver Tagesmüdigkeit und Einschlafneigung in monotonen Situation ist, berichten Patienten mit Herzinsuffizienz häufig über nächtliche Luftnot, häufiges Wasserlassen und unruhigen Schlaf. Durch die Atempausen kommt es zu Sauerstoffmangel, Aktivierung des sympathischen Nervensystems und zu ständigen Weckreaktionen, die die normale Schlafstruktur zerstören. Herzinsuffiziente Patienten, die an diesem Atemmuster leiden, haben nicht nur eine schlechtere Lebensqualität, sondern auch eine kürzere Lebenserwartung als Menschen mit Herzinsuffizienz ohne Cheyne-Stokes-Atmung.
Studien zur CPAP-Therapie bei Herzinsuffizienz konnten Verbesserungen der Auswurffraktion über Zeiträume von 1 und bzw. 3 Monaten zeigen. Zusätzlich konnte eine Verbesserung der Lebensqualität und eine Abnahme der Stresshormone nachgewiesen werden. Des Weiteren konnte eine deutliche Reduktion des Blutdrucks gezeigt werden.
Ferner konnte gezeigt werden, dass die Anzahl der nächtlichen Atmungsstörungen reduziert ist. Der Effekt ist jedoch abhängig vom verwendeten Therapiedruck, ein dauerhaft zu hoher Beatmungsdruck kann sich auch schädlich auf das Kreislaufsystem auswirken.
Zur Prüfung der Hypothese, dass eine nächtliche optimierte Atemtherapie (adaptive Servoventilation) die Prognose herzinsuffizienter Patienten bessert, wurde jetzt die Serve-HF-Studie aufgelegt, deren Design und EinschluÃkriterien (chronisch stabile Herzinsuffizienz und prädominant zentrale Schlafapnoe) im Vortrag besprochen werden.
Fazit: Schlafbezogene Atmungsstörungen treten häufig bei Patienten mit einer chronischen Herzinsuffizienz auf. Sie führen zu einer Verschlechterung der Herzinsuffizienz und sind ein negativer prognostischer Marker für das Ãberleben der Patienten. Bei therapierefraktären Patienten sollte eine Abklärung diesbezüglich sowie eine Therapieeinleitung in Erwägung gezogen werden. Es ist zu empfehlen die Patienten derzeit zunächst in Studien einzuschleusen.
Abstract: In spite of success in the management of heart failure, repetitive rehospitalisation and high mortality rate remain a serious problem. Recent studies, especially the COMPANION trial, have demonstrated that cardiac resynchronisation therapy (CRT) reduces mortality and rehospitalisation in heart failure patients. There is also evidence that telemonitoring of heart failure patients potentially reduces both mortality and morbidity. Recently, a Home Monitoring (HM) function has been integrated into BIOTRONIK CRT-defibrillators and CRT-pacemakers with a view of harnessing the powerful combination of CRT with close remote monitoring of heart failure patients. It is possible now to transmit predefined parameters on a daily basis from the implanted devices to a web-based platform accessible by patients' physicians. Our study evaluates clinical usefulness of Biotronik HM function in CRT-defibrillators and CRT-pacemakers.
Abstract: Background
Endothelin receptor antagonism produces favorable short-term hemodynamic effects in heart failure, but the clinical effects of longer term therapy have not been evaluated.
Methods and results
Three hundred and seventy patients with symptoms of heart failure at rest or on minimal exertion and a left ventricular ejection fraction <35% were randomly assigned (double-blind) to placebo (n = 126) or the endothelin receptor antagonist bosentan, titrated slowly (n = 121) or rapidly (n = 123) to a target dose of 500 mg twice daily. Treatment with the study drug was to be maintained for 26 weeks, whereas background medications for heart failure were kept constant. Safety concerns led to early termination of the trial when only 174 patients had had an opportunity to complete 26 weeks of therapy. Bosentan exerted no apparent benefit when all randomized patients were analyzed (P = .709). However, in the first 174 patients who were recruited at least 26 weeks before study termination and who could therefore be followed for the planned duration of the trial, patients in the bosentan groups were more likely to be improved (26% versus 19%) and were less likely to be worse (28% versus 43%), P = .045. When compared with placebo-treated patients, bosentan-treated patients had a increased risk of heart failure during the first month of treatment but a decreased risk of heart failure during the fourth, fifth, and sixth months of therapy. The major noncardiac adverse effects of bosentan included an increase in hepatic transaminases (in 15.6% of patients) and a decrease in hemoglobin (of about 1 g/L).
Conclusion
Although bosentan exerted no favorable effects in the overall study, our findings suggest that the clinical responses to endothelin antagonism with bosentan in patients with severe chronic heart failure may be dependent on the duration of treatment.
Abstract: OBJECTIVES: The VIP registry investigated the efficacy of preventive pacing algorithm selection in reducing atrial fibrillation (AF) burden. BACKGROUND: There are few data identifying which patients might benefit most from which preventive pacing algorithms. METHODS: Patients, with at least one documented AF episode and a conventional antibradycardia indication for pacemaker therapy, were enrolled. They received pacemakers with AF diagnostics and four preventive algorithms (Selection and PreventAF series, Vitatron). A 3-month Diagnostic Phase with conventional pacing identified a Substrate Group (>70% of AF episodes with <2 premature atrial contractions [PACs] before AF onset) and a Trigger Group (< or =70% of AF episodes with <2 PACs before AF onset). This was followed by a 3-month Therapeutic Phase where in the Trigger Group algorithms were enabled aimed at avoiding or preventing a PAC and in the Substrate Group continuous atrial overdrive pacing was enabled. RESULTS: One hundred and twenty-six patients were evaluated. In the Trigger Group (n = 73), there was a statistically significant 28% improvement in AF burden (median AF burden: 2.06 hours/day, Diagnostic Phase vs 1.49 hours/day, Therapy Phase; P = 0.03304 signed-rank test), and reduced PAC activity. There was no significant improvement in AF burden in the Substrate Group (median AF burden: 1.82 hours/day, Diagnostic Phase vs 2.38 hours/day, Therapy Phase; P = 0.12095 signed-rank test), and little change in PAC activity. CONCLUSIONS: We identified a subgroup of patients for whom the selection of appropriate pacing algorithms, based on individual diagnostic data, translated into a reduced AF burden. Trigger AF patients were more likely responders to preventive pacing algorithms as a result of PAC suppression.
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