Abstract: Late loss is becoming an important end point to compare drug-eluting stents; however, little is known about its pattern of distribution. We analyzed the pattern of late loss distribution in sirolimus-eluting stents (SESs) and paclitaxel-eluting stents (PESs) in a consecutive cohort of patients. From a cohort of 529 patients treated with drug-eluting stents in 1 year, we selected all patients who underwent angiographic follow-up. Three hundred fifty-nine patients with 592 de novo lesions received SESs (286 lesions) or PESs (306 lesions). Late loss and binary angiographic restenosis were analyzed. Binary restenosis occurred in 56 lesions (19.6%) treated with SESs compared with 53 (17.3%) treated with PESs (p = 0.48). The 2 late loss distributions were skewed to the right and were not normally distributed (p <0.001 for SES, p = 0.003 for PES). Late loss was significantly lower in the SES group (p = 0.03), with a median value of 0.29 mm (interquartile range -0.09 to 0.66) versus 0.41 mm (-0.02 to 0.85) in the PES group. When analyzing only restenotic lesions, late loss had a normal distribution in the SES and PES groups (p = 0.96 and 0.44, respectively) and was similar in the 2 groups (1.75 +/- 0.51 vs 1.82 +/- 0.62, p = 0.48). When evaluating nonrestenotic lesions, late loss was also normally distributed in the 2 groups (p = 0.75 for SES, p = 0.73 for PES) but was significantly lower (p = 0.002) after SES implantation (0.14 +/- 0.39) than after PES implantation (0.27 +/- 0.44). In conclusion, SESs and PESs have a bimodal pattern of late loss distribution. The observed difference in late loss between SES and PES seems to be partly explained by the decrease in late loss after SES implantation in nonrestenotic lesions (where SES approaches "zero late loss"). Thus, late loss may not be a reliable marker of the true efficacy of these devices due to its complex and nongaussian distribution.
Abstract: BACKGROUND: Currently, little data are available on the management of drug-eluting stent (DES) restenosis. Drug resistance may play a role in its etiology. METHODS: We identified all cases of either sirolimus-eluting or paclitaxel-eluting stent restenosis treated with repeated DES implantation. The lesions were divided into those receiving the same DES as the one that restenosed and those treated with the alternative DES. The end points analyzed were target lesion revascularization (TLR) and angiographic restenosis. RESULTS: We included 201 lesions (174 patients); the same DES was implanted in 107 lesions and a different DES in 94 lesions. Angiographic follow-up of the retreatment was available in 69.7% of the lesions. Angiographic restenosis occurred in 26.4% (19) of cases treated with the same DES and 25.8% (17) of those treated with a different DES (P = 1.0). Target lesion revascularization occurred in 15.9% (17) and 16% (15) of lesions, respectively (P = 1.0). A multivariate analysis confirmed the lack of association between the treatment selected and TLR (OR 0.7, 95% CIs [0.29-1.67]; P = .42). A nonfocal pattern of restenosis remained associated with TLR and restenosis (OR 2.99, 95% CIs [1.24-7.24]; P = .015 and OR 3.6, 95% CIs [1.5-8.8]; P = .004, respectively). CONCLUSIONS: Repeated DES implantation for DES restenosis is feasible and safe. The TLR rate is acceptable, with no differences between implantation of the same or a different DES. The pattern of restenosis treated is an important predictor of outcomes.
Abstract: The "apical ballooning" is a cardiac syndrome characterized by acute extensive but reversible akinesia of the apex and mid part of the left ventricle (LV), without obstructive coronary artery disease (CAD), triggered by emotional or physical stress, accompanied by chest pain and/or dyspnoea, electrocardiographic changes mimicking acute coronary syndromes (ACS), and minimal but, to date, obligatory release of cardiac enzymes. Today the precise aetiology remains unknown, but prognosis is generally excellent. We hereby report a unique case of a 60-year-old woman presenting with transient wide anterolateral akinesia and severe LV dysfunction with persistently normal myocardial markers, despite the extent of wall motion abnormalities. This clinical vignette is the first proof of the concept that timely recognition and management may be able to prevent myocardial necrosis in patients with apical ballooning syndrome.
Abstract: BACKGROUND: Treatment of bifurcation stenoses (BS) by percutaneous coronary intervention (PCI) remains challenging, even with drug-eluting stents (DES). We aimed to appraise clinical, myocardial scintigraphy and late (>9 months) exploratory angiographic outcomes of provisional T-stenting in the management of BS. METHODS: We enrolled 53 consecutive patients with BS in the proximity of a greater than or equal to 2 mm side branch (SB). The provisional T-technique was performed in all cases, with implantation of DES in the main branch (MB), SB balloon-only dilatation, and final kissing in the event of >50% SB stenosis. Provisional SB-stenting (using another DES) was reserved to cases with persisting >50% stenosis/dissection and reduced TIMI flow. Further kissing inflation was recommended in such patients. Stress/rest single-photon emission computed tomography (MIBI) and coronary angiography follow up were scheduled >6 and 9 months after PCI, respectively. RESULTS: Major adverse cardiac events at 14 +/- 3 months occurred in 5 patients (9.4% [95% confidence interval 0.1-17.4%]: 1 (1.9% [0.1-5.8%]) non-Q-wave myocardial infarction for subacute stent thrombosis, 2 (3.8% [0.1-9.0%]) target lesion revascularizations and 2 (3.8% [0.1-9.0%]) target vessel revascularizations. Six-month MIBI was performed in 51 patients (96.3%): 4 patients had positive results (7.8% [0.2-15.4%]). Angiography was performed in 4 of these patients and in another 27 patients, with clinical restenosis occurring overall in only 5 (16.1% [8.9-23.3%]), 1 case of clinical restenosis in the MB (3.2% [0.6-9.4%]), and 4 in the SB (12.9% [5.1-24.9%]). CONCLUSIONS: This study suggests the safety and efficacy of provisional T-drug-eluting stent implantation in bifurcation coronary lesions, and supports the use of follow-up myocardial scintigraphy, with angiography reserved for selected patients and lesions.
Abstract: BACKGROUND: Patients at risk of sudden cardiac death (SCD) after myocardial infarction (MI) can currently be offered effective means of prevention, such as implantable cardioverter-defibrillators (ICD). However, predictors of SCD able to identify those patients who are at higher risk are still lacking. Whether C-reactive protein (CRP), a serum inflammatory marker with established prognostic accuracy after MI, can also be a predictor of SCD is unclear. METHODS: The CAMI GUIDE study is designed to evaluate the prognostic role of CRP in patients undergoing ICD implantation after MI according to MADIT II criteria (i.e. left ventricular ejection fraction<or=30%). CAMI GUIDE is a prospective observational study aimed at assessing the role of CRP in the risk-stratification of SCD after MI. CRP will be measured on the basis of a pre-specified cut-off value of 3 mg/l, before and 1 month after ICD implantation; clinical follow-up will last 24 months. The primary endpoint is the combined rate of SCD or fast ventricular tachycardia/ventricular fibrillation. Secondary endpoints will be total mortality, death due to acute coronary syndromes, death from pump failure, non-fatal MI, coronary revascularization, hospitalization for congestive heart failure or unstable angina and inappropriate ICD shocks. Twenty-four Italian centers will participate in enrollment of the 290 patients planned according to power analysis. CONCLUSIONS: The CAMI GUIDE study will assess the predictive role of CRP in SCD in patients with previous MI undergoing ICD implantation. Its results will improve risk stratification, thereby enabling better-tailored and more cost-effective therapies to be undertaken in those patients whose need is greatest.
Abstract: BACKGROUND: Studies focusing on short- and mid-term follow up support the beneficial role of sirolimus-eluting stents (SES) in the treatment of in-stent restenosis (ISR), yet no long-term safety and/or efficacy data are available. METHODS: Patients with ISR following bare-metal stenting (BMS) and treated with SES were prospectively studied. Baseline, procedural, and in-hospital data were appraised. The primary endpoint was the rate of major cardiovascular events (MACE) at long-term follow up (>9 months). Secondary endpoints were the individual contributors to MACE. RESULTS: A total of 180 SES were implanted to treat 138 consecutive patients. Procedural success was achieved in all patients without in-hospital death, acute stent thrombosis, stroke, or urgent coronary artery bypass. During follow up, MACE occurred in 5.8% of patients at 6 months, 14.3% at 12 months, and 25% at 24 months. Specifically, all-cause mortality was 1.7% at 6 months, 3.5% at 12 months, and 4.8% at 24 months, for a total of 5 deaths. Target vessel revascularization occurred at 6, 12, and 24 months in 4.2%, 11.2%, and 15.9% of patients, respectively, while target lesion revascularization (TLR) alone accounted for 3.4% at 6 months, 9.6% at 12 months, and 11% at 24 months. Three case of myocardial infarction occurred during follow up (2.2%), without any surgical revascularization or stent thrombosis. CONCLUSIONS: Treatment of ISR with SES appears safe and effective, even if a 10% annual rate of MACE can be expected, with a sizable portion of these due to apparently nontarget lesion events.
Abstract: Coronary revascularization procedures by means of percutaneous coronary interventions or coronary artery bypass graft surgeries are performed worldwide daily for the symptomatic treatment of patients with myocardial ischaemia. Nevertheless, angina remains a significant clinical problem. Management of angina recurring or persisting after coronary revascularization is particularly challenging. This review attempts to summarize the most common causes of recurrent chest pain after coronary revascularization, to analyse the possible diagnostic approaches, and to discuss the potential treatment modalities.
Abstract: BACKGROUND: Clopidogrel is an established alternative to ticlopidine in addition to aspirin after coronary stenting because of its safety, but its optimal initial dosing is unclear. We performed a systematic review and meta-regression of randomized clinical trials comparing clopidogrel versus ticlopidine, focusing on clopidogrel front-loading. METHODS: PubMed was searched for pertinent studies (updated August 2006). Random-effect odds ratios (ORs) with 95% CIs were computed for death or nonfatal myocardial infarction, and weighted least squares random-effect meta-regression was performed to explore the impact of loading versus nonloading clopidogrel scheme. RESULTS: We retrieved 7 trials (3382 patients, average follow-up of 7 months). In 5 studies, both clopidogrel and ticlopidine were started with a loading dose, in 1 trial clopidogrel was administered without loading, and in 1 trial clopidogrel could be administered with or without loading. Overall analysis (P for heterogeneity = .02) showed similar results for clopidogrel and ticlopidine (OR 0.90, 95% CI 0.44-1.84, P = .77). In studies administering clopidogrel with loading, this treatment was, however, significantly better than ticlopidine (OR 0.60, 95% CI 0.36-0.99, P = .05). This significant interaction between clopidogrel loading and its superiority in comparison with ticlopidine was also formally confirmed by meta-regression (beta = -0.64, P = .012). CONCLUSIONS: This work supports the superiority of a clopidogrel regimen including an initial loading dose in comparison with ticlopidine in patients undergoing coronary stenting.
Abstract: Arterial revascularization by means of percutaneous transluminal angioplasty (PTA) is a mainstay in the management of patients with peripheral artery disease and critical limb ischemia (CLI). However, when employing standard approaches, percutaneous transluminal angioplasty (PTA) of below-the-knee arteries may fail in up to 20% of cases. In the present article, we report on a novel interventional strategy, the pedal-plantar loop technique, which we successfully employed in a patient with critical lower limb ischemia. This technique may sensibly increase success rates of PTA in very challenging total occlusions of below-the-knee arteries (e.g., those lacking a proximal occlusion stump). Technical points pertinent to this case are clearly illustrated, including the need to accurately choose guidewires and balloons of appropriate length, and the extensive use of the subintimal angioplasty technique.
Abstract: Antegrade femoral artery access is commonly used for percutaneous transluminal revascularization of ipsilateral lower limbs in patients with critical limb ischemia. While hemostasis at the end of the procedure can be achieved by manual compression, this may lead to an increase in local vascular complications. Femoral artery closure devices, such as the Angioseal collagen plug and anchor device, have been approved and shown of benefit after retrograde femoral artery catheterization. To date, there are however no data on the use of such arteriotomy closure device after antegrade femoral access. We hereby report a case series of five patients in whom Angioseal was successfully used after antegrade femoral puncture and below-the-knee percutaneous transluminal angioplasty. In all cases the device enabled immediate and complete hemostasis without major complications, despite the intense antithrombotic regimen, including heparin, aspirin, and clopidogrel in all patients, as well as glycoprotein IIb/IIIa inhibitors (in two patients) and fibrinolytic therapy (in one).
Abstract: There is ongoing debate to identify the most effective, safe and cost-beneficial drug-eluting stent, between the two currently approved and used devices, i.e. sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). To date, head-to-head comparison studies of SES vs PES have been however limited by relatively small sample sizes and the low number of events typically associated with these highly effective coronary devices. To overcome the drawbacks of single trials, direct and indirect comparison meta-analyses have been designed and conducted to thoroughly compare sirolimus- vs paclitaxel eluting-stents. This article provides results of a pooled analysis of such indirect and direct comparisons, definitively demonstrating across 5854 patients the superiority of SES in comparison to PES (odds ratio 0.62 [95% confidence interval 0.50-0.75], p<0.0001 for binary angiographic restenosis, and odds ratio 0.66 [0.52-0.84], p=0.0008 for target lesion revascularization). Indeed, such combination of direct and indirect comparisons should also be envisaged to soundly and timely appraise the next generation of drug-eluting stents.
Abstract: Antegrade femoral artery access is often used for diagnostic and interventional purposes in patients with critical limb ischemia, given its potential advantages in terms of visualization and back-up. However, it may be associated with an increased risk of local vascular complications, especially in the presence of common femoral artery atherosclerosis. We hereby report a case of antegrade femoral access in a previously stented common artery, which enabled successful recanalization of a totally occluded superficial femoral artery. Despite the procedural success, retroperitoneal bleeding occurred after sheath removal, which was nonetheless effectively managed with prolonged balloon inflations by means of contralateral femoral artery access. This clinical vignette, the first to date to report on antegrade access in a stented femoral artery, supports its feasibility despite the presence of a real bleeding risk.
Abstract: BACKGROUND: Paclitaxel-eluting stents (PES) have been proved effective in randomized trials enrolling highly selected patients. Yet, given the uncertainty concerning results of PES implantation in very high-risk patients and lesions, we designed a prospective multicenter registry, the Taxus in Real-life Usage Evaluation (TRUE) Study. STUDY DESIGN, PATIENT CHARACTERISTICS AND IN-HOSPITAL OUTCOMES: Consecutive patients undergoing PES implantation were enrolled provided that the target lesion treated with PES was an unprotected left main (ULM), a true bifurcation, a chronic total occlusion (CTO), a long lesion (>28 mm), located in a small vessel (<2.75 mm), or the patient had diabetes mellitus. Clinical events will be adjudicated at 1, 7 and 12 months, with 4- to 8-month angiographic follow-up. The primary end-point will be the 7-month occurrence of major adverse cardiovascular events (MACE, i.e. the composite of cardiac death, non-fatal myocardial infarction [MI], coronary artery bypass grafting [CABG] and percutaneous target vessel revascularization [TVR]). To date, patient enrollment has been completed reaching the target of 1065 subjects. These included 322 (30.2%) diabetics, 115 (10.8%) subjects undergoing PES implantation for ULM, 229 (21.5%) in a bifurcation, 191 (17.9%) in a CTO, 430 (40.4%) in a small vessel, and 289 (27.1%) in a long lesion. An average of 1.5+/-0.6 vessels and 2.0+/-1.0 lesions were treated per patient, with 2.0+/-1.2 PES implanted per patient, and a 46+/-30 mm total PES length per patient. In-hospital MACE occurred in 39 (3.7%) patients, with 2 (0.2%) cardiac deaths, 32 (3.0%) MI, 5 (0.5%) TVR, no CABG, and 4 (0.4%) acute stent thromboses. IMPLICATIONS: Despite the availability of randomized trials, only carefully designed and prospective registries can provide timely and accurate assessment of the risk-benefit profile of PES in very high-risk patients. Indeed, the TRUE Study, including as much as 115 ULM and 229 bifurcation interventions, should give important insights into the outcome of PES in such an unprecedented and challenging context.
Abstract: Apoptosis is a pathologic feature of cardiomyocytes in acute myocardial infarction (AMI) and heart failure. The temporal course of apoptosis in the peri-infarct area in the weeks following an AMI is still uncompletely defined. In order to study the time course of apoptosis after AMI, 16 rabbits underwent left coronary artery ligation and were sacrificed at 16, 26, 35, and 56 days after surgery. Increased apoptotic rate (AR) was observed at in the peri-infarct region than in remote myocardium (5.4% [2.5-9.6] vs 0.4% [0.1-0.9], respectively, P<0.001) and than in sham-operated cases (0.01% [0-0.02], P<0.001). A gradual decrease of AR in the peri-infarct region was observed over time with a 90% reduction at 8 weeks after coronary ligation.
Abstract: The present review aims to describe the pharmacological aspects as well as the available clinical data supporting the choice of intracoronary route of administration for abciximab, an antiplatelet drug used in patients with acute coronary syndromes undergoing percutaneous coronary interventions (PCI). Abciximab is a glycoprotein (GP) IIb/IIIa receptor antagonist which determines a potent inhibition of platelet aggregation and thrombus formation. These properties seem to prevent not only thrombus formation but also to promote (at higher drug concentration) lysis of fresh thrombus. Moreover, differently from the other GP IIb/IIIa inhibitors, abciximab also binds to the vitronectin receptor on endothelial, smooth muscle, and inflammatory cells and to an activated conformation of the aMb2 receptor on leukocytes. Such cross-reactivity raises the possibility that clinical benefits derived from its use may not be exclusively due to its anti-thrombotic effect, but may also be related to the suppression of inflammatory pathways involving platelets, white blood cells, and the vascular endothelium. On such basis, the local administration of abciximab at the site of coronary thrombosis may enhance, by increasing its local concentration, the binding to both platelet and endothelium receptors. The results of several angiographic studies assessing the effect of intracoronary abciximab administration support on clinical grounds its adoption in patients with fresh coronary thrombosis. Indeed, better post-angioplasty coronary flow, greater degree of myocardial salvage and a better left ventricular function recovery have been achieved as compared to the intravenous, systemic, administration of drug's bolus. Condensed Abstract Several studies have highlighted the benefits of abciximab, a potent antiplatelet agent, in patients with acute coronary syndromes undergoing percutaneous coronary interventions. Moreover, differently from the other glycoprotein IIb/IIIa receptor antagonists, abciximab also has non-IIb/IIIa-related properties raising the possibility that clinical benefits derived from its use may not be exclusively due to its anti-thrombotic effect, but may also be related to the suppression of inflammatory pathways. Several angiographic studies in patients with fresh coronary thrombosis and recent clinical studies in patients with acute coronary syndromes undergoing mechanical revascularization support the hypothesis that local administration of abciximab at the site of the culprit coronary artery may facilitate both the de-thrombotic and the non-GP IIb/IIIa-dependent properties of the drug. On such basis, the present review aims to describe the pharmacological aspects as well as the available clinical data supporting the choice of intracoronary route of administration for abciximab.
Abstract: Heart failure is a complex syndrome characterized by impaired emptying and/or impaired filling of the heart chambers. The use of parameters of diastolic function has provided novel tools for risk stratification and management of patients with heart failure. This study evaluated the potential correlation between apoptosis at time of death and left ventricular (LV) diastolic function after acute myocardial infarction. We selected, at routine postmortem examination, 14 subjects who died 10 to 62 days after an acute myocardial infarction and had an available echocardiographic report from the most recent hospital admission. The apoptotic rate was calculated at the region bordering the infarct, using co-localization of in situ end-labeling for deoxyribonucleic acid fragmentation and immunohistochemistry for caspase-3. Transthoracic echocardiographic studies were retrospectively reevaluated and pulse-wave Doppler spectra of mitral inflow were analyzed. LV diastolic function was assessed by measuring the ratio of E peak velocity to A peak velocity and E-wave deceleration time; a ratio of E peak velocity to A peak velocity >or=2 and deceleration time <115 ms were considered a restrictive filling pattern. A restrictive pattern was found in 4 cases (29%). All subjects with a restrictive pattern were symptomatic for New York Heart Association class IV heart failure (100% vs 20%, p = 0.015) and had larger transverse heart diameters at pathology (p = 0.014). The apoptotic rate in the peri-infarct region was significantly higher in patients with a restrictive versus nonrestrictive diastolic pattern (13%, 10 to 14, vs 3%, 1 to 6, p = 0.014). At multivariable analysis that included the restrictive pattern, class IV heart failure, and cardiac diameters, the restrictive pattern remained an independent predictor of increased apoptosis (p = 0.030). In conclusion, patients with severe postinfarction LV diastolic dysfunction had significantly higher rates of cardiomyocyte loss by apoptosis, which may partly explain their unfavorable outcome.
Abstract: Overlapping homogenous drug-eluting stents (DESs) may be used instead of overlapping bare metal stents (BMSs) to treat coronary lesions longer than available stents. Yet, no data are available on patients treated with overlapping heterogenous DESs or DESs and BMSs. We prospectively assessed 9-month clinical outcome and 6-month angiographic late loss (evaluated at 5 different lesion segments) in a consecutive series of 40 patients who received overlapping homogenous DESs (sirolimus-eluting stent [SES] or paclitaxel-eluting stent [PES]), heterogenous DESs (SES + PES), or overlapping DESs and BMSs. In 8 patients (7 with angiographic follow-up) with overlapping heterogenous DESs, no angiographic or clinical adverse event was observed. Moreover, in-segment late loss was similar to that of patients who received homogenous DESs. In 8 patients (7 with angiographic follow-up) with overlapping DESs and BMSs, there was a higher incidence of major adverse events (3 repeat percutaneous coronary interventions and 1 death, 50% adverse event rate) and worse in-segment binary restenosis rate compared with patients treated with homogenous or heterogenous DESs (p = 0.02 and 0.012, respectively). Late lumen loss at the site of stent overlap showed significant differences according to type of overlapped stent (1.00 +/- 0.76 mm in DES-BMS overlap, 0.32 +/- 0.55 mm in PES-PES overlap, 0.13 +/- 0.11 in SES-PES overlap, and 0.08 +/- 0.10 mm in SES-SES overlap, p = 0.005). In conclusion, the present study suggests that overlap of DESs and BMSs should be avoided because the antirestenotic effect of DESs is skewed by contiguous BMS implantation. Overlap between SESs and PESs in this very preliminary report was associated with no specific adverse event.
Abstract: BACKGROUND: The oral direct thrombin inhibitor ximelagatran, and its active form, melagatran, have been tested in various clinical conditions as a promising alternative to conventional anticoagulant therapy (CAT), despite some concerns over potentially serious liver injury. OBJECTIVES: To assess its risk/benefit profile, a systematic review and meta-analysis of all randomised controlled trials (RCTs) comparing xi-/melagatran to CAT was performed. METHODS: Leading medical databases were searched. The rates of major adverse events (MAE: all cause death, nonfatal myocardial infarction, nonfatal thromboembolic stroke, nonfatal pulmonary embolism), major bleeds (MB), and hepatotoxicity were compared. Out of 140 potentially relevant citations, 13 RCTs enrolling 22,639 patients were included. Indications for treatment were: 1) perioperative prophylaxis of deep vein thrombosis (DVT); 2) management of DVT; and 3) stroke prevention in atrial fibrillation. RESULTS: Overall, the risk of MAE (OR 0.98 [0.83-1.17]) and MB (OR 1.01 [0.69-1.47]) did not differ significantly between xi-/melagatran and CAT. There was a clear trend towards an increased risk of hepatotoxicity (OR 1.74 [0.50-6.01]), with an incidence of 5.8% with xi-/melagatran versus 2.3% with CAT (p<0.001); more specifically, the rate of hepatotoxicity was markedly augmented in the management of DVT (OR 5.16 [3.38-7.89]), for treatment durations > or = 3 months (OR 6.73 [5.01-9.05]), and in the prevention of atrial fibrillation-related stroke (OR 8.31 [5.65-12.23]). Two fatal cases of liver injury occurred with xi-/melagatran. CONCLUSIONS: Although comparable to CAT in terms of MAE and MB, xi-/melagatran carries a prohibitive risk of hepatotoxicity that cannot be ignored. Newer long-term alternatives are urgently needed.
Abstract: To assess the temporal effect of statin therapy on coronary atherosclerotic plaque volume measured by intravascular ultrasound (IVUS), we searched PubMed for eligible studies published between 1990 and January 2006. Inclusion criteria for retrieved studies were (1) IVUS volume analysis at baseline and follow-up and (2) statin therapy in > or =1 group of patients. All data of interest were abstracted in prespecified structured collection forms. Statistical analysis was performed with Review Manager 4.2. Random-effect weighted mean difference (WMD) was used as summary statistics for comparison of continuous variables. Nine studies of 985 patients (with 11 statin treatment arms) were selected. After a mean follow-up of 9.8 +/- 4.9 months, we found a significant decrease in coronary plaque volume (WMD -5.77 mm(3), 95% confidence interval -10.36 to -1.17, p = 0.01), with no significant heterogeneity across studies (p = 0.47). Prespecified subgroup analyses showed similar trends. Studies in which the achieved low-density lipoprotein (LDL) cholesterol level was <100 mg/dl showed a trend for plaque regression (WMD -7.88 mm(3), 95% confidence interval -16.31 to 0.55, p = 0.07), whereas studies in which the achieved level of LDL cholesterol was > or =100 mg/dl, the trend was less evident (WMD -4.22 mm(3), 95% confidence interval -10.27 to 1.82, p = 0.17). Plaque volume remained essentially unchanged in patients not treated with statins (WMD 0.13 mm(3), 95% confidence interval -4.42 to 4.68, p = 0.96). In conclusion, statin therapy, particularly when achieving the target LDL level, appears to promote a significant regression of coronary plaque volume as measured by IVUS.
Abstract: BACKGROUND: Acute kidney injury is common in critically ill patients. Fenoldopam mesylate is a potent dopamine A-1 receptor agonist that increases blood flow to the renal cortex and outer medulla. Because there is uncertainty about the benefits of fenoldopam in such a setting, we performed a systematic review of randomized controlled trials of intensive care unit patients or those undergoing major surgery. METHODS: BioMedCentral, CENTRAL, PubMed, and conference proceedings were searched (updated October 2005). Investigators and external experts were contacted. Two unblinded reviewers selected randomized controlled trials that used fenoldopam in the prevention or treatment of acute kidney injury in postoperative or intensive care patients. Studies involving the prevention of contrast nephropathy or containing duplicate data were excluded from analysis. Two reviewers independently abstracted patient data, treatment characteristics, and outcomes. RESULTS: A total of 1,290 patients from 16 randomized studies were included in the analysis. Pooled estimates showed that fenoldopam consistently and significantly reduced the risk for acute kidney injury (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.32 to 0.59; P < 0.001), need for renal replacement therapy (OR, 0.54; 95% CI, 0.34 to 0.84; P = 0.007), and in-hospital death (OR, 0.64; 95% CI, 0.45 to 0.91; P = 0.01). These benefits were associated with shorter intensive care unit stay (weighted mean difference, -0.61 days; 95% CI, -0.99 to -0.23; P = 0.002). Sensitivity analyses, tests for small-study bias, and heterogeneity assessment further confirmed the main analysis. CONCLUSION: This analysis suggests that fenoldopam reduces the need for renal replacement and mortality in patients with acute kidney injury. A large, multicenter, appropriately powered trial will need to be performed to confirm these results.
Abstract: OBJECTIVES: To overview and summarize the results emerging from the studies on adjunctive devices (AD) with theoretical anti-embolic properties in patients with ST-elevation acute myocardial infarction (STEMI) undergoing percutaneous coronary interventions (PCI). BACKGROUND: A series of small-to-medium size randomized studies have compared different AD with standard PCI (SP) in the setting of STEMI. The reported results are conflicting. METHODS: Eighteen prospective randomized studies on 3180 STEMI patients comparing AD with SP were identified and entered the meta-analysis. Pre-specified angiographic, electrocardiographic (absence of ST-segment resolution, STR) and early (up to 30 days) clinical end-points were assessed. RESULTS: AD were associated with lower rates of angiographically evident distal embolization: OR (95% CI): 0.54 (0.37-0.81). Analyses of angiographic and electrocardiographic reperfusion showed striking heterogeneity among studies and an overall trend toward better results with AD: OR (95% CI) 0.76 (95% CI 0.51-1.12) for TIMI<3, 0.53 (0.37-0.76) for myocardial blush grade (MBG)<3, 0.60 (0.45-0.78) for absence of STR. Subgroup analysis according to the type of AD for the end-point of no STR showed concordant absence of benefit in studies testing distal protection devices, positive results being confined to the studies using thrombectomy devices (OR 0.46, 95% CI 0.32-0.66). However, the possibility of a "small study" bias within thrombectomy studies cannot be discharged (significant heterogeneity and positive Egger's test). Early major adverse cardiac events were not different between AD and SP. CONCLUSIONS: AD use may be associated with reduced rate of angiographic distal embolization, and improved MBG 3 and STR rates. However, efficacy might vary with the type of device employed. Moreover, early clinical outcome is not modified suggesting that further, larger, studies are needed to assess the clinical impact of AD. CONDENSED ABSTRACT: We conducted a meta-analysis of 18 prospective randomized trials comparing adjunctive devices (AD) with standard PCI in the setting of STEMI. The use of AD was associated with lower rates of (angiographically evident) distal embolization. Analyses of angiographic and electrocardiographic reperfusion showed striking heterogeneity and an overall trend toward better results with AD. Subgroup analysis suggested that different types of device may have different effects. Early major adverse cardiac events were similar between AD and SP.
Abstract: OBJECTIVES: To evaluate the superiority of the paclitaxel-eluting stent (PES) in reducing neointimal hyperplasia (NIH) over its corresponding bare metal stent (BMS) during primary percutaneous coronary intervention (PCI). BACKGROUND: Primary PCI with stent implantation is the repercussion strategy of choice for ST-elevation myocardial infarction (STEMI); nonetheless restenosis rate is still high. Drug-eluting stents have been proven to reduce restenosis rate in many settings, but their use during primary PCI is still controversial. METHODS: Consecutive patients with STEMI <12 hours were randomized to receive PES or BMS. The primary end-point was the percentage of the stent volume obstructed by neointimal proliferation (NIH) measured by intravascular ultrasound (IVUS) at a 7-month angiographic follow-up. Secondary end-points were binary restenosis rate and major adverse cardiac events (MACE, i.e., death, nonfatal myocardial infarction, and target lesion revascularization). RESULTS: Eighty patients with STEMI were randomized into the PES or BMS group. Patients were well matched for baseline characteristics and the index procedure was always successful. In-hospital and 1-month MACE were 2.5% per group. NIH at 7 months was 4.6% versus 20% (P< 0.01), late lumen loss 0.1 versus 1.01 mm (P = 0.01). MACE were 7.5% versus 42.5% (P = 0.001) with no difference in death and recurrent myocardial infarction rates. Late-acquired incomplete stent apposition (ISA) rate was 5.1% versus 2.7% (P = 0.65). One subacute stent thrombosis was reported in each group. CONCLUSIONS: PES was superior to its corresponding BMS in reducing NIH in the STEMI setting without any increase in early and long-term clinical adverse events.
Abstract: OBJECTIVES: The authors performed a meta-analysis to investigate whether the cardioprotective effects of volatile anesthetics translate into decreased morbidity and mortality in patients undergoing cardiac surgery. BACKGROUND: It is commonly believed that the choice of the primary anesthetic agent does not result in different outcomes after cardiac surgery. Recent evidence, however, has indicated that volatile anesthetics improve postischemic recovery at a cellular level, in isolated hearts, in animals, and in humans. METHODS: Four investigators independently searched BioMedCentral and PubMed. Inclusion criteria were random allocation to treatment and comparison of a total intravenous anesthesia regimen versus an anesthesia plan including desflurane or sevoflurane performed on cardiosurgical patients. Exclusion criteria were duplicate publications, nonhuman experimental studies, and no outcome data. The endpoints were the rate of perioperative myocardial infarction and hospital mortality. RESULTS: The search yielded 22 studies, involving 1,922 patients. Volatile anesthetics were associated with significant reductions of myocardial infarctions (24/979 [2.4%] in the volatile anesthetics group v 45/874 [5.1%] in the control arm, odds ratio [OR] = 0.51 [0.32-0.84], p for effect = 0.008, and p for heterogeneity = 0.77) and mortality (4/977 [0.4%] v 14/872 [1.6%], OR = 0.31 [0.12-0.80], p for effect = 0.02, and p for heterogeneity = 0.88). CONCLUSIONS: Desflurane and sevoflurane have cardioprotective effects that result in decreased morbidity and mortality. The present data show for the first time that the choice of an anesthetic regimen based on administration of halogenated anesthetics is associated with a better outcome after cardiac surgery.
Abstract: Identification of so-called "vulnerable plaque" or "high-risk" plaques have spawned manifold attempts to develop diagnostic tools capable to afford this task. This task is particularly challenging but the reward is high: local intervention on identified "vulnerable plaque" could preclude plaque thrombosis and possibly prevent acute coronary syndromes. Various imaging techniques are currently under investigation by extensive clinical testing to identify which could become the most sensible and specific modality for vulnerable plaque detection. Noninvasive techniques are fascinating for their easily applicability to a broad population but nowadays are not sufficiently powered for this task. The emerging technologies with the greatest resolution are indeed catheter-based and many intravascular modalities have been developed for identification of "vulnerable plaque". Among these, IVUS-Virtual Histology (IVUS-VH) is the most promising technique in the field. IVUS-VH offers an in vivo opportunity to assess plaque morphology and histology. IVUS-VH uses underlying frequency information along with echoes intensity, while grey-scale IVUS data are obtained from echoes of different intensity or amplitude. The major advantage of IVUS-VH is that it is based on a device that is practical for use in the clinical setting and that it generates a real-time assessment of plaque morphology. Unfortunately, numerous challenging issues still need to be overcome until the numerous "vulnerable plaques" could be identified and successfully treated. Future efforts may identify plaques that are on a trajectory of evolution toward a vulnerable state, and help us target interventions to those plaques most likely to develop plaque disruption and related complications.
Abstract: Favorable early results of percutaneous drug-eluting stents in unprotected left main (LM) disease are available, but outcome data beyond 6 to 10 months are lacking. We evaluated the long-term results of sirolimus-eluting stents (SESs) in patients with LM disease. From November 2002 to December 2004, consecutive patients with LM disease, without contraindications to double antiplatelet therapy and undergoing SES implantation, were enrolled prospectively. The primary end point of the study was occurrence of major adverse cardiovascular events. In total 85 patients were treated with 118 SES and followed for 595 +/- 230 days. Event-free survival rates at 1 year and 2 years were 85.5% and 78.6%, respectively. Only 2 deaths occurred overall (2.4%), the first in-hospital in a very high-risk patient according to the European System for Cardiac Operative Risk Evaluation and the second in a patient with severe systolic dysfunction already at the index procedure). Myocardial infarction was adjudicated in 3 patients (3.6%), 2 occurring periprocedurally and 1 during follow-up for a de novo nontarget lesion. There were 7 (10.8%) target lesion revascularizations at 24 months, with all but 1 percutaneous and in a subject with bifurcation LM disease at baseline. At 9-month angiography, late loss was 0.15 +/- 0.81 mm and restenosis rate was 8.2%. An increased incidence of adverse events was noted in patients undergoing SES after dilation with extremely oversized balloons. No case of stent thrombosis was reported. In conclusion, this single-center experience suggests that percutaneous use of SESs to treat LM disease in unselected high-risk patients is safe and effective even 1 year after implantation.
Abstract: Background Due to the recently published results of the MAGIC study there is confusion as to whether administration of granulocyte-colony stimulating factor (G-CSF) after acute myocardial infartion (MI) should be regarded as a potentially harmful treatment. This meta-analysis of appropriate clinical studies is intended to show the impact of G-CSF given after MI on aggravated incidence of coronary restenosis or progression of coronary lesions. Methods and Results We used a fixed effects model based on the Mantel-Haenszel method to combine results from the different trials. These studies provided the basis for the current analysis comprising 106 patients of whom 62 were subjected to G-CSF treatment. <BR> Minimum lumen diameter (MLD) measured immediately after percutaneous coronary intervention (PCI) was similar in both groups with a diameter stenosis of 12.3+/-9.5 percent in the G-CSF and 10.3+/-8.5 percent in the control group (p=0.32). At follow-up, both MLD and percent stenosis were not different between G-CSF-treated and control patients. Subsequently, averaged late lumen loss revealed similar results and no differences between groups (p=0.11), and neither stent thrombosis nor reinfarction in either group. Conclusions The current meta-analysis of clinical reports fails to justify an elevated risk for coronary restenosis after PCI in acute MI or adverse events following G-CSF in the setting of MI when used after state of the art treatment in carefully conducted clinical protocols.
Abstract: OBJECTIVES: We aimed to perform a meta-analysis of clinical trials on intracoronary cell therapy after acute myocardial infarction (AMI). BACKGROUND: Intracoronary cell therapy continues to be evaluated in the setting of AMI with variable impact on left ventricular ejection fraction (LVEF). METHODS: We searched the CENTRAL, mRCT, and PubMed databases for controlled trials reporting on intracoronary cell therapy performed in patients with a recent AMI (< or =14 days), revascularized percutaneously, with follow-up of > or =3 months. The primary end point was change in LVEF, and secondary end points were changes in infarct size, cardiac dimensions, and dichotomous clinical outcomes. RESULTS: Ten studies were retrieved (698 patients, median follow-up 6 months), and pooling was performed with random effect. Subjects that received intracoronary cell therapy had a significant improvement in LVEF (3.0% increase [95% confidence interval (CI) 1.9 to 4.1]; p < 0.001), as well as a reduction in infarct size (-5.6% [95% CI -8.7 to -2.5]; p < 0.001) and end-systolic volume (-7.4 ml [95% CI -12.2 to -2.7]; p = 0.002), and a trend toward reduced end-diastolic volume (-4.6 ml [95% CI -10.4 to 1.1]; p = 0.11). Intracoronary cell therapy was also associated with a nominally significant reduction in recurrent AMI (p = 0.04) and with trends toward reduced death, rehospitalization for heart failure, and repeat revascularization. Meta-regression suggested the existence of a dose-response association between injected cell volume and LVEF change (p = 0.066). CONCLUSIONS: Intracoronary cell therapy following percutaneous coronary intervention for AMI appears to provide statistically and clinically relevant benefits on cardiac function and remodeling. These data confirm the beneficial impact of this novel therapy and support further multicenter randomized trials targeted to address the impact of intracoronary cell therapy on overall and event-free long-term survival.
Abstract: Combined antiplatelet treatment with aspirin and clopidogrel is pivotal to minimize periprocedural adverse events in patients who undergo percutaneous coronary intervention. However, there is debate on the best clopidogrel loading dose. The investigators performed a systematic review and meta-analysis of the optimal clopidogrel loading dose. Pertinent trials comparing high (>300 mg) and standard (300 mg) clopidogrel loading doses in patients scheduled for catheterization and/or percutaneous coronary intervention were systematically searched in BioMedCentral, CENTRAL, Google Scholar, and PubMed (December 2006). The primary end point was the 1-month rate of death or myocardial infarction. Secondary end points included other ischemic and bleeding adverse effects. Peto odds ratios were computed. A total of 10 studies (7 randomized, 3 nonrandomized) were included, enrolling 1,567 patients (712 loaded with 300 mg, 11 with 450 mg, 790 with 600 mg, and 54 with 900 mg). Overall, a high loading dose proved significantly superior to a standard loading dose in preventing cardiac death or nonfatal myocardial infarction (odds ratio 0.54, 95% confidence interval 0.32 to 0.90, p = 0.02), without any statistically significant increase in major or minor bleedings (p = 0.55 and p = 0.98, respectively). Sensitivity analysis restricted to randomized trials confirmed the superiority of a high loading dose regimen (p = 0.0031). Meta-regression disclosed a significant interaction between event rate and the benefits of high loading doses (p = 0.005), suggesting that the greater the underlying risk, the greater the favorable impact of a high loading dose. In conclusion, a high clopidogrel loading dose (>300 mg) significantly reduces early ischemic events in patients scheduled for percutaneous coronary intervention.
Abstract: BACKGROUND: Percutaneous coronary intervention (PCI) has been increasingly employed to treat unprotected left main coronary artery (LMCA) stenosis, with variable success. This strategy has been applied to patients undergoing drug-eluting stent (DES) implantation for unprotected LMCA stenosis. METHODS: From April 2003 to June 2006, 114 consecutive patients with de novo unprotected LMCA stenosis underwent PCI with DES, and were followed over a mean period of 17.1 +/- 9.1 months. The primary endpoint of the study was the occurrence of major adverse cardiovascular events (MACE) (cardiac death, myocardial infarction [MI] or target lesion revascularization [TLR]). RESULTS: LMCA stenting was successfully performed in all patients. In-hospital mortality was 3.5%, with no in-hospital non-fatal MI or emergency coronary artery bypass grafts. During the follow-up period, the all-cause mortality rate was 7.9%, with 3.5% cardiac-related deaths. TLR was performed in 7.9% of patients, and the MACE rate was 14.9%. All non-surviving patients were at high surgical risk (EuroSCORE > 6) and had a significantly higher EuroSCORE than surviving patients that patients with a EuroSCORE < or = 11 had significantly improved survival rates over those with a EuroSCORE > 11 (p < 0.0001). Moreover, most of the patients who died of cardiac causes were diabetic (71.4% vs. 26.6%; p < 0.05). Acute coronary syndromes, as clinical presentation, and non-ostial LMCA disease were also significantly more common within non-surviving patients (100% vs. 67%; p < 0.05, and 92.3% vs. 66.3%; p = 0.05, respectively). CONCLUSIONS: Stenting of unprotected LMCA appears to be associated with a favorable mid-term outlook, especially in selected patients.
Abstract: Dual antiplatelet therapy is a mainstay in the management of patients undergoing coronary stenting. Whether this is also appropriate in patients with a diagnosis of idiopathic thrombocytopenic purpura (ITP) is unclear. We report the case of a 66-year-old man with ITP admitted for an acute coronary syndrome. On admission platelets were 110x10(9)/L without petechiae or purpura, and coronary angiography revealed multivessel disease with significant left main involvement. Given the unfeasibility of surgical revascularization with cardiopulmonary bypass because of ITP, a staged percutaneous revascularization strategy was chosen. Both left circumflex and right coronary arteries were treated with bare-metal stenting during the index admission. After 4 weeks of strict clinical monitoring and evidence of a stable total platelet count on oral prednisone, percutaneous coronary intervention with drug-eluting stenting was performed in the left main and left anterior descending arteries. He was then discharged on lifelong aspirin and a 6-month clopidogrel regimen without thrombotic or bleeding complications. Given the paucity of data on ITP and stenting, no strict recommendations can be proposed and treatment should be individualized to minimize both bleeding and thrombosis risks. Nonetheless, this case suggests the feasibility of percutaneous revascularization in selected patients with multivessel coronary disease and ITP.
Abstract: Despite encouraging results from randomized trials, concerns exist about long-term results of sirolimus-eluting stent implantation. We sought to determine whether in-stent restenosis occurring >1 year ("late") after sirolimus-eluting stent implantation is a real clinical entity. We analyzed data on all sirolimus-eluting stents implanted in our institution before March 2003. During the study period 928 lesions in 433 patients were treated. Angiographic follow-up was performed in 306 patients (70.6%) with 679 lesions (73.2%). Angiography after 1 year was performed only in symptomatic patients. We considered restenosis "early" if it occurred during the first year and late if after 1 year. Late restenosis required demonstration of a widely patent stent at 6 to 9 months, with repeat angiography after 1 year demonstrating restenosis. Restenosis occurred in 160 lesions overall (23.5%). Of the 31 (4.6%) that were documented after 1 year, 13 were excluded from analysis due to absence of 6- to 9-month angiography; the remaining 18 (2.6%, 1.7 to 4.2) fulfilled our criteria for late restenosis (median time of documentation 607 days, interquartile range 511 to 923). In conclusion, late restenosis is an infrequent but real entity; its existence implies we should not discount the possibility of restenosis as the cause of symptoms that develop >1 year after sirolimus-eluting stent implantation.
Abstract: Background. T-lymphocyte activation within atherosclerotic plaque, and widespread to the myocardium has been shown in patients with acute coronary syndromes. Aim To investigate the presence of T-lymphocyte infiltrate at different stages of acute coronary syndromes by studying patients with sudden coronary death, acute myocardial infarction and healed infarction, in comparison to patients with myocarditis and patients with non-ischemic heart failure. Methods. Seventy-two cases were studied at autopsy: 12 dying of sudden coronary death (Group 1), 12 dying <4 weeks (Group 2) and 12 dying >4 months after AMI (Group 3), 12 with active lymphocytic myocarditis (Group 4), 12 with hypertensive heart disease (Group 5), and 12 control subjects (Group 6). Light-microscopy was performed to measure the number of activated T-lymphocytes (CD3+/DR+) in the myocardium and coronary artery wall, and intercellular adhesion molecule-1 (ICAM-1) expression in the myocardium. Results. Activated T-lymphocyte infiltrates and ICAM-1 myocardial expression in both remote and peri-infarction regions and activated T lymphocytes within the epicardial coronary artery wall both the infarct- and non-infarct-related arteries were found in Groups 1,2 and 3, whereas myocardial, but not coronary, infiltrates were found in Groups 4 (P<0.001 vs Groups 1,2 and 3 for coronary infiltrates). Groups 5 and 6 had no evidence of myocardial or coronary inflammation (P<0.001 vs Groups 1,2 and 3). Conclusions. This study shows for the first time the presence of a lymphocytic infiltrate in both coronaries and myocardium and a pro-inflammatory phenotype shift in the myocardium associated with acute coronary thrombosis in patients dying suddenly, shortly, or even late after coronary thrombosis.
Abstract: OBJECTIVE: To assess changes in cardiac function in animals with ischemic congestive heart failure (CHF) treated with a selective cyclo-oxygenase-2 (COX-2) inhibitor. BACKGROUND: In patients with CHF, COX-2 expression was associated with features of worsening failure. However, evidence of beneficial or detrimental functional effects of COX-2 inhibition in ischemic CHF is lacking. METHODS: Thirty male Wistar rats underwent coronary ligation and were allowed to recover for 12 months. Five sham-operated animals were used as controls. After 12 months, six surviving animals underwent baseline echocardiogram to measure end-diastolic diameter (EDD), end-systolic diameters (ESD), fractional shortening (FS), and anterior and posterior diastolic and systolic wall thicknesses. The animals were thereafter treated by daily intraperitoneal parecoxib injections (0.75 mg/kg) for 7 days. On day 7, a repeat echocardiogram was performed. RESULTS: When compared to baseline, repeat echocardiography after 7 days of parecoxib treatment showed no changes in the EDD (9.4 +/- 0.4 mm vs. 9.4 +/- 0.3 mm, P = 0.9), a significant reduction of ESD (5.5 +/- 0.8 mm vs. 6.4 +/- 0.3 mm, P = 0.028), and a significant improvement in the FS (43 +/- 3% vs. 32 +/- 5%, P = 0.027). Improvement of FS was associated with a significant change in systolic thickness in the infarct zone (3.6 +/- 0.4 mm vs. 3.0 +/- 0.1 mm, P = 0.046), whereas no significant changes in systolic thickness in the remote area were observed. CONCLUSIONS: Administration of parecoxib in ischemic CHF provides functional improvement of the peri-infarct myocardium. This finding may prove useful in improving quality of life and, perhaps, survival in patients with ischemic heart disease.
Abstract: OBJECTIVES: The aim of the study was the assessment of the clinical, angiographic and procedural characteristics correlated with freedom from adverse events at 1 year in a real life setting of consecutive bifurcation lesions. BACKGROUND: Even if stent implantation has shown to be superior to conventional balloon angioplasty in most coronary lesions, bifurcation treatment with stent implantation both in main and in side branch (SB) still raises controversy. METHODS: We reviewed the results obtained in a prospective multicenter registry of 150 patients with 158 bifurcation lesions involving a SB of sufficient diameter to be treated, if necessary, with a polymer based paclitaxel eluting stent (PES, TAXUS). Two stents were used in 118 lesions (74.7%). Final kissing balloon inflation was performed in 87/118 lesions (73.7%) and in 30/40 lesions (75.0%) of the 2 and 1 stent group respectively. RESULTS: At 1-year clinical follow-up we observed 4 stent thromboses, all involving the SBs of the 2 stents group (2.7%). Unlike previous reports, revascularization involved the main vessel in the majority of patients (21/150, 14.0%). After an exploratory multivariable analysis the only parameter predictive of target lesion revascularization (TLR) (HR 0.52; CI 95% 0.11-0.86; p = 0.02) and target vessel revascularization (TVR) (HR 0.47; CI 95% 0.14-0.90; p = 0.03) was postprocedural main branch minimal lumen diameter (MB-MLD). CONCLUSIONS: In a real life setting of consecutive bifurcation lesions, thrombosis rate, concentrated in the SB and the 2-stents group, and need for target lesion revascularization remain higher than in less complex lesion subgroups treated with PES. No differences in immediate success and TLR were observed between 2 stents and 1 stent groups. The frequently observed suboptimal stent expansion and final MB-MLD predict 1 year revascularization.
Abstract: We report on a case of a fatal pulmonary embolism--an unexpected finding at autopsy of a 71-year-old man who had suffered from severe erosive gouty arthritis. Using morphological findings, medical history and histopathological results, we show the potentially devastating complications of this fairly common medical condition, occurring as a result of massive bone marrow erosion and detachment and finally leading to embolization of the lungs.
Abstract: The direct thrombin inhibitor, ximelagatran, and its active form, melagatran (X/M), have been compared against conventional anticoagulant therapy (CAT) in many clinical settings. Their risk-benefit profile drove large debate until withdrawal by the manufacturer. A systematic review of all published randomized trials has been performed and a meta-analysis of randomised controlled trial (RCT) of X/M versus CAT. Major medical databases were searched for RCTs. Major adverse events (MAE: all cause death, nonfatal myocardial infarction, nonfatal thromboembolic stroke, pulmonary embolism), major bleeds (MB), minor bleeds and the rate of hepatotoxicity (HT) were compared. In terms of efficacy, X/M was at least as effective as, or even superior to, CAT. In terms of safety, the overall risk of MAE, MB, minor bleeds and HT was not significantly different for X/M compared with CAT. According to individual clinical settings, X/M was associated with a lower risk of MB but a prohibitive higher risk of HT in those clinical settings requiring prolonged treatment.
Abstract: After acute coronary syndromes, the beneficial effect of aspirin plus clopidogrel (A+C) or aspirin plus dose-adjusted warfarin (A+W) compared with aspirin alone is well established. However, these regimens were never compared. To compare the risk-benefit profile of A+C versus A+W after acute coronary syndromes, major medical databases for randomized controlled trials comparing 1 of these combined approaches versus aspirin alone after an acute coronary syndrome (updated June 2006) were searched. Evaluated end points were major adverse events [MAEs: all-cause death, acute myocardial infarction [AMI], thromboembolic stroke, major bleeds, and overall risk of stroke [hemorrhagic or ischemic]). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for (1) A+W versus aspirin alone, (2) A+C versus aspirin alone, and (3) A+W versus A+C using adjusted indirect meta-analysis. Thirteen studies were included, totaling 69,741 patients. Ten compared A+W versus aspirin alone and 3 compared A+C versus aspirin alone. Each combined approach yielded a significantly lower risk of MAEs, albeit an increased risk of major bleeds, compared with aspirin alone. No significant difference was found for A+W versus A+C for risk of overall MAEs, death, or AMI. However, A+W versus A+C was associated with a significantly lower risk of thromboembolic stroke (OR 0.53, 95% CI 0.31 to 0.88, number needed to treat 60) and all types of stroke (OR 0.58, 95% CI 0.35 to 0.94, p=0.038), but also with increased risk of major bleeds (OR 1.9, 95% CI 1.2 to 2.8, number needed to harm 300). In conclusion, after an acute coronary syndrome, A+W and A+C are comparable in the prevention of MAEs, death, and AMI compared with aspirin alone. Allocating 100 patients to A+W (at international normalized ratio 2 to 3) with respect to A+C could prevent 17 thromboembolic strokes while causing 3 major bleeds.
Abstract: INTRODUCTION: Although stenting has been shown to reduce the need for target vessel revascularization (TVR) in acute myocardial infarction (AMI), the benefits in terms of mortality and reinfarction are still unclear. Previous meta-analyses have failed to include all currently available randomized trials. The aim of the current study was to perform an updated meta-analysis to evaluate the benefits of coronary stenting for AMI in terms of mortality, reinfarction, and TVR, and whether these benefits correlated with the patient's risk profile. METHODS: The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL) from January 1990 to September 2006. We examined all completed, published, randomized trials of coronary stenting for AMI. The following key words were used for study selection: randomized trial, myocardial infarction, reperfusion, primary angioplasty, rescue angioplasty, stenting, and balloon angioplasty. Information on study design, type of stent, inclusion and exclusion criteria, primary endpoint, number of patients, angiographic and clinical outcome, were extracted by two investigators. Disagreements were resolved by consensus. RESULTS: A total of 13 randomized trials were identified and analyzed involving 6922 patients (3460 or 50% randomized to stent and 3462 or 50% to balloon). Stenting was not associated with a significant reduction in 30-day (2.9% versus 3.0%, p=0.81) and 1-year mortality (5.1% versus 5.2%, p=0.81), as compared to balloon angioplasty. However, a significant relationship was observed between patient's risk profile and mortality benefits from coronary stenting at 30-day (beta -0.63 [-25.4; -2.45], p=0.022) and 1-year follow-up (beta -0.61 [-15.9; -0.76], p=0.034). Stenting was associated with benefits in terms of TVR at both 30-day (3.1% versus 5.1%, p<0.0001) and 6 to 12 months (11.3% versus 18.4%, p<0.0001) follow-up, without any difference in terms of reinfarction. CONCLUSIONS: Among AMI patients undergoing primary angioplasty, coronary stent implantation, when anatomically and technically feasible, may be considered, in addition to benefits in terms of TVR, to reduce mortality in high-risk patients, who may be identified by the use of validated risk scores.
Abstract: Stroke is the second cause of mortality in industrialized countries. Atherosclerotic plaque rupture with atheromatous debris distal embolization is the pathogenetic mechanism responsible for cerebrovascular events due to atherosclerotic carotid disease. Plaque composition rather than lesion burden seems to be the determinant factor producing rupture and subsequent thrombosis. Histologic features of vulnerability are : a large lipid core, a thin fibrous cap, and an inflammatory infiltrate rich of monocytes and macrophages. In the clinical practice, it is difficult to predict the risk of experiencing a major cerebrovascular events especially in asymptomatic patients. New invasive techniques such as intravascular ultrasound with termography, optical coherence tomography, fotons spectroscopy and elastography have been developed to detect atherosclerotic lesion tissue composition. However, such techniques are difficult to apply on a large scale basis in primary prevention. On the contrary, new serologic biomarkers such as Pregnancy Associated Plasma Protein-A, Lp-PLA2, Interleukin-6, Interleukin-12, metalloproteinases, lipoprotein-(a), and plaque oxidative products have been recently proposed for screening general and high risk population. The present paper will briefly review the current histologic characteristics of vulnerable plaque and the new imaging tools proposed for its detection, focusing on the most recent serologic biomarkers evaluated in the clinical practice to increase our accuracy in predicting not only the plaque but moreover the patient at risk for an acute cerebrovascular event.
Abstract: OBJECTIVES: This study was designed to compare the outcomes of paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES) in a contemporaneous cohort of real-world patients. BACKGROUND: A number of randomized comparisons of PES and SES have shown unequivocal advantages for SES in angiographic end points such as late loss. However, the data on clinical outcomes are less consistent. METHODS: All consecutive patients successfully treated with only SES or PES in de novo native vessel lesions between March 2003 and March 2005 were analyzed. Our end points were major adverse cardiac events (MACE), a composite of death, myocardial infarction (MI), target vessel revascularization (TVR), and target lesion revascularization (TLR). We also analyzed late loss and angiographic restenosis. RESULTS: There were 609 patients (1,064 lesions) treated with PES and 674 patients (1,205 lesions) treated with SES. Diabetes mellitus was present in 26.8% of patients and multivessel disease in 75% of patients. Bifurcations made up 16.3% of lesions, chronic occlusions 9.5%, left main 4.8%, and American Heart Association/American College of Cardiology type B2/C 75.4%. Despite a higher late loss in the PES group (p = 0.0001), there were no differences in angiographic restenosis (PES 18% vs. SES 17.8%, p = 0.95), TLR (PES 11.9% vs. SES 11%, p = 0.47), or MACE (PES 21.3% vs. SES 21.1%, p = 0.95). The relative risk of MACE for the PES group was 1.02 (95% confidence interval [CI] 0.78 to 1.33). Multivariable analysis confirmed the lack of association of stent type with MACE (odds ratio 1.03 [95% CI 0.77 to 1.38], p = 0.83) and TLR (odds ratio 1.08 [95% CI 0.81 to 1.44], p = 0.61). CONCLUSIONS: In this complex cohort, both stent platforms demonstrated similar clinical outcomes despite different late loss.
Abstract: Clinical symptoms of acute or chronic myocardial ischemia due to congenital coronary anomalies occasionally develop during adult life. While several types of coronary anomalies have been already reported, origin of the coronary arteries outside of the ascending aorta and pulmonary trunk is exceedingly rare, and has indeed been described to date only in a 6-day-old newborn. We hereby report to the best of our knowledge the first and unique case of an adult patient with ischemic cardiomyopathy, in whom coronary angiography and aortography disclosed both left main trunk hypoplasia and subsidiary left coronary supply provided by an ectopic artery arising from the descending thoracic aorta.
Abstract: AIMS: Coronary dissections left untreated after percutaneous coronary intervention are associated with unfavourable outcomes. However, their role after drug-eluting stent (DES) implantation is still undescribed. We assessed incidence, predictors, and outcomes of residual dissections in DES-treated lesions. METHODS AND RESULTS: Consecutive patients undergoing DES implantation were enrolled in four Italian centres, with baseline, procedural, and outcome data entered into a dedicated database. Residual dissections were classified according to the National Heart Lung and Blood Institute criteria. End-points of interest were in-hospital, 1-month, and 6-month major adverse cardiovascular events (MACE, i.e. death, myocardial infarction, or target vessel revascularization), and stent thrombosis (ST). Among the 2418 included patients (4630 lesions), a total of 77 (1.7%) final dissections occurred in 67 (2.8%) subjects. Dissections were more frequent in longer and complex lesions and in the left anterior descending, and were associated with increased rates of in-hospital (11.9 vs. 5.2%, P=0.017) and 1-month MACE (13.4 vs. 6.0%, P=0.013), with similar 6-month trends. Cumulative ST was also greater in patients with dissections (6.3 vs. 1.3%, P=0.011). Even non-obstructive dissections with thrombolysis in myocardial infarction 3 flow conferred a significantly worse prognosis. CONCLUSION: This study, reporting for the first time on incidence, predictors, and outcomes of residual dissections in DES-treated coronary lesions, demonstrates their adverse clinical impact and supports the pursuit of a strategy of sealing dissection flaps with other DES.
Abstract: Thienopyridines and aspirin are beneficial in patients undergoing bare-metal stent implantation, and aspirin and clopidogrel treatment have also been proved effective after drug-eluting stent (DES) implantation. However, despite the common substitution of clopidogrel with ticlopidine because of cost or patient intolerance, there are no data on the comparison of ticlopidine vs. clopidogrel after DES implantation. We hereby compare ticlopidine vs. clopidogrel after paclitaxel-eluting stent implantation in subjects enrolled in the prospective multicenter Taxus in Real-life Usage Evaluation (TRUE) Study. Across the 505 analyzed patients (112 treated with ticlopidine and 393 with clopidogrel), similar rates of early and mid-term (7 months) adverse thrombotic events were found with either antiplatelet regimen, with the notable exception of 2 cases of late stent thrombosis in patients who had prematurely withdrawn ticlopidine treatment just 3 months after the procedure. These findings thus support the overall safety and effectiveness of ticlopidine after DES implantation, and also confirm the increased risk of late thrombosis when premature withdrawal of thienopyridines occurs.
Abstract: AIMS: In patients recovering from acute coronary syndromes (ACS) the role of oral anticoagulation (and its intensity) in addition to aspirin remains controversial. We conducted a specific meta-analysis of randomized trials comparing aspirin plus warfarin (A+W) with aspirin alone in such patients. METHODS AND RESULTS: MEDLINE and Cochrane databases yielded 14 (of 148 potentially relevant) articles enrolling 25 307 patients. Follow-up ranged from 3 months to 5 years. Irrespective of International normalized ratio (INR), A+W did not significantly affect the risk of major adverse events (MAE: all cause death, non-fatal myocardial infarction, and non-fatal thrombo-embolic stroke) when compared with aspirin alone [OR 0.96 (0.90-1.03), P=0.30], but increased the risk of major bleeds (MB): OR 1.77 (1.47-2.13), P<0.00001. However, in studies with INR of 2-3, A+W was associated with a significant reduction of MAE [OR 0.73 (0.63-0.84), P<0.0001, number needed to treat to avoid one MAE=33], albeit at an increased risk of MB [OR 2.32 (1.63-3.29), P<0.00001; number needed to harm by causing one MB=100]. In both analyses, intracranial bleeding was not significantly increased by A+W when compared with aspirin alone. CONCLUSION: For patients recovering from ACS, a combined strategy of A+W at INR values of 2-3 doubles the risk of MB, but is nonetheless superior to aspirin alone in preventing MAE. Whether this combined regimen is also superior to a 'double' anti-platelet strategy or to newer evolving treatments warrants further investigation.
Abstract: In patients with in-stent restenosis (ISR) inside bare metal stents, drug-eluting stents reduce the recurrence of restenosis compared with balloon angioplasty. However, few data are available about this therapeutic modality in the case of diffuse restenosis. The aim of this study was to evaluate the immediate and mid-term outcome of sirolimus- and paclitaxel-eluting stent implantation in diffuse ISR and determine the predictors of clinical and angiographic restenosis recurrence. A series of 161 consecutive patients with 194 diffuse ISR lesions (>10 mm) treated with drug-eluting stent implantation were evaluated. Major adverse cardiac events were defined as death, myocardial infarction, and the need for target lesion revascularization. During a mean follow-up of 8.2 +/- 3.4 months, the cumulative incidence of major adverse cardiac events was 19% in the SES group and 24% in the PES group (p = 0.56). Angiographic follow-up was performed in 80% of the lesions. The overall restenosis rate was 22% and was not significantly different between lesions treated with sirolimus-eluting (20%) or paclitaxel-eluting (25%, p = 0.55) stents. The incidence of restenosis was higher in diabetics (32%) than in nondiabetics (16%, odds ratio 2.5, 95% confidence interval 1.1 to 5.5, p = 0.02). By multivariate analysis, diabetes was confirmed to be the only independent predictor of recurrent restenosis (odds ratio 3.53, 95% confidence interval 1.39 to 9.02, p = 0.008). In conclusion, drug-eluting stent implantation for diffuse ISR is associated with acceptable clinical and angiographic results. The association of diffuse restenosis and diabetes mellitus is an unfavorable condition leading to a high risk of recurrence.
Abstract: Vessel perforation is an uncommon but potentially life-threatening complication of percutaneous coronary intervention and is often associated with the use of atheroablative devices. While effective management means are currently available, such as PTFE-covered stent, pericardiocentesis, and perfusion balloon, a timely and skillful approach is of paramount importance to solve this dreadful complication. We hereby describe a case of saphenous vein graft (SVG) perforation occurring after cutting balloon angioplasty for in-stent restenosis. Despite the immediate occurrence of cardiac arrest due to massive extravasation of contrast in the mediastinum with pericardial tamponade, deep catheter intubation enabled the deployment of two PTFE-covered stents and subsequent sealing of the leak with repeated inflation of a perfusion balloon, while hemopericardium was drained by pericardiocentesis. This clinical vignette emphasizes the role of optimal backup in order to deploy life-saving devices and successfully manage life-threatening pericardial tamponade due to SVG rupture.
Abstract: OBJECTIVE: To test the hypothesis that impaired coronary and myocardial blood flow are linked with increased myocyte apoptosis, thus establishing a link between pressure overload and left ventricular (LV) remodelling. METHODS AND RESULTS: Peak diastolic coronary blood flow velocity (CBFV) was evaluated at transthoracic Doppler echocardiography, and signal intensity (SI) and the rate of SI rise (beta) were measured at myocardial contrast echocardiography in 11 patients with severe aortic stenosis and LV hypertrophy. In the same patients, biopsies were obtained from the anterolateral LV free wall during surgery and analysed for cardiomyocyte apoptosis. LV mass corrected CBFV (CBFVI) was significantly lower in patients than in controls (median 0.100 cm.g/s (interquartile range 0.07-0.115) v 0.130 cm.g/s (0.130-0.160), p = 0.002). Similarly, SI*beta was significantly lower in patients than in controls (11 1/s (8-66) v 83 1/s (73-95), p = 0.001). Apoptotic rate was increased in aortic stenosis more than 100-fold versus controls (1.2% (0.8-1.4) v 0.01% (0.01-0.01), p < 0.001) and inversely correlated with lower CBFVI and SI*beta (r = -0.77, p = 0.001 for both). CONCLUSIONS: Patients with severe aortic stenosis and LV hypertrophy have impaired myocardial perfusion, which is associated with enhanced cardiomyocyte apoptosis. Impaired myocardial perfusion and the ensuing oxygen demand-supply imbalance may, at least partially, be responsible for increased apoptosis and possible transition to heart failure, thus establishing a link between pressure overload, LV remodelling, and heart failure.
Abstract: BACKGROUND: Diffuse coronary artery ectasiae (DCE) are occasionally found at necropsy or at angiography. Pathogenetic mechanisms of DCE are still poorly known. Matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs) and vascular endothelial growth factor (VEGF) are involved in vascular remodeling and may play a role in DCE. METHODS: A total of 1280 consecutive coronary angiograms performed in a single institution in 1 year were screened. DCE were found in 15 patients. Diagnosis at hospital admission was acute coronary syndromes in all of them. Two patients died during initial admission and 1 refused blood sampling; the remaining 12 patients were enrolled in the study. No patient with DCE exhibited coronary stenoses. Plasma levels of VEGF, MMP-2, TIMP-1, TIMP-2 and C-reactive protein (CRP) were measured in these 12 patients 12 months after discharge during a silent clinical phase, in 12 age- and sex-matched patients with stable angina (SA) and coronary artery disease, and in 12 age- and sex-matched patients with normal coronary arteries (NCA). RESULTS: VEGF levels were higher in patients with DCE than in SA or NCA (151.6 pg/ml [36.2-252.9] vs. 66.6 pg/ml [36.4-93.3] and 54.8 pg/ml [14.5-87.1], respectively, p = 0.012]. TIMP-2 levels were lower in DCE and SA than in NCA (5.9 ng/ml [0-33.6] and 5.0 [0-17.4] vs. 139.3 ng/ml [114.4-237.4], respectively, p < 0.001). TIMP-1 and MMP-2 plasma levels were similar in all groups (p = NS), and CRP levels were within normal limits (< 3 mg/L) in most patients, irrespective of their coronary anatomy (75% for DCE, 66% for SA, and 84% for NCA [p = NS]). CONCLUSIONS: Symptomatic patients with DCE typically present with an acute coronary syndrome and exhibit lack of obstructive stenosis at angiography, decreased plasma levels of TIMP-2 and raised plasma levels of VEGF. The simultaneous occurrence of reduced MMPs inhibition and increased angiogenetic activity suggests an accelerated and persistent extracellular matrix remodeling process favouring arterial remodeling and aneurysms formation which is likely to enhance the risk of thrombosis because of low shear stress.
Abstract: OBJECTIVE: To appraise multiple systematic reviews on the same clinical topic, focusing on predictors and correlates of quality of reporting of meta-analysis (QUOROM) scores. DESIGN: Case study. SETTING: Reviews providing at least individual quantitative estimates on role of acetylcysteine in the prevention of contrast associated nephropathy. DATA SOURCES: PubMed, the database of abstracts of reviews of effects, and the Cochrane database of systematic reviews (updated March 2005). MAIN OUTCOME MEASURES: Funding, compliance with the QUOROM checklist, scores on the Oxman and Guyatt quality index, and authors' recommendations. RESULTS: 10 systematic reviews, published August 2003 to March 2005, were included. Nine pooled events despite heterogeneity and five recommended routine use of acetylcysteine, whereas the remaining studies called for further research. Compliance with the 18 items on the QUOROM checklist was relatively high (median 16, range 11 to 17), although shorter manuscripts had significantly lower scores (R = 0.73; P = 0.016). Reviewers who reported previous not for profit funding were more likely to score higher on the Oxman and Guyatt quality index. No association was found between QUOROM and Oxman and Guyatt scores (R = -0.06; P = 0.86), mainly because of greater emphasis of the Oxman and Guyatt scores on the appraisal of bias in selection and validity assessment (inadequate in five reviews). CONCLUSIONS: Multiple systematic reviews on the same clinical topic varied in quality of reporting and recommendations. Longer manuscripts and previous not for profit funding were associated with higher quality.
Abstract: Non-invasive diagnosis of coronary artery disease (CAD) in patients with left ventricular (LV) dysfunction and left bundle branch block (LBBB) remains challenging, and there is no consensus on the role of myocardial sesta-MIBI perfusion scintigraphy with pharmacological stress (dip-MIBI) or dipiridamole echocardiography (dip-ECHO). We thus performed a prospective study to test the diagnostic accuracy of such non-invasive tests. 27 consecutive patients with both LV dysfunction and LBBB undergoing diagnostic work-up for CAD were studied simultaneously with dip-ECHO and dip-MIBI. The sensitivity for CAD for dip-ECHO and dip-MIBI was respectively 42% and 67%, with specificity 93% and 53%, and likelihood ratio (LR)-positive 6.3 and LR-negative 0.6 for both. Given the low accuracy of both dip-ECHO and dip-MIBI in detecting CAD in patients with concomitant LV dysfunction and LBBB, coronary angiography should be performed as the default diagnostic strategy in such patients.
Abstract: Late luminal loss after percutaneous coronary intervention, although not normally distributed, has been shown to be monotonically correlated with the probability of binary angiographic restenosis after drug-eluting stent implantation. A recently proposed method has been shown to predict the restenosis rate after sirolimus-eluting stent and paclitaxel-eluting stent implantation using a power transformation of the value of late loss obtained after implantation of the 2 stent types. We used the same method to compute and compare restenosis rates from late loss values observed in the "head-to-head" randomized sirolimus-eluting stent versus paclitaxel-eluting stent comparisons available thus far. Our results showed that the model proposed has a poor overall ability to predict the real incidence and relative risk of restenosis because the use of late loss as an end point tended to overestimate the difference in restenosis, and the derived effect estimate of 1 stent compared with that of the other seemed to be overemphasized with respect to the real risk. We thus believe that further investigations are needed to appraise the real clinical effect of late loss and its reliability as an end point in direct comparative drug-eluting stent trials before its use can be recommended as a clinical surrogate.
Abstract: BACKGROUND: We sought to compare, using meta-analytic techniques, bare-metal stent versus balloon angioplasty in the percutaneous treatment of total coronary occlusions by means of a quantitative systematic review and to indicate new avenues for future treatments. METHODS: MEDLINE and CENTRAL were searched. Inclusion criteria were random allocation, prospective comparison, and intention to treat. Random-effect odds ratios (ORs) with 95% confidence intervals (CIs) for death, myocardial infarction (MI), repeated revascularization, major adverse cardiac events (MACE), and angiographic restenosis and reocclusion were computed. RESULTS: Nine trials (1409 patients) were included. Death rate was not different in the 2 groups, 0.4% after stenting versus 0.7% after balloon angioplasty (OR 0.72, 95% CI 0.21-2.50). MI rate was significantly increased after stenting (6.7% vs 3.4%, OR 2.06, 95% CI 1.22-3.46), mainly because of a higher rate of periprocedural non-Q-wave MI. By contrast, the risk of repeated revascularization was significantly reduced by stenting (17% vs 32%, OR 0.41, 95% CI 0.31-0.53). This yielded to an overall reduction in the rate of MACE after stenting (23.2% vs 35.4%, OR 0.49, 95% CI 0.36-0.68). Angiographic restenosis and reocclusion were also decreased by stent (41.1% vs 60.9%, OR 0.36, 95% CI 0.23-0.57; 6.8% vs 16%, OR 0.36, 95% CI 0.22-0.59, respectively). CONCLUSIONS: In total coronary occlusions, stenting yields an important benefit over balloon angioplasty in reduction of MACE, repeated revascularizations, and angiographic restenosis and reocclusion. However, these events remain frequent. Moreover, the finding of an increased rate of periprocedural minor myocardial damage after stenting casts caution. New strategies aimed to reduce the need of repeated revascularizations and periprocedural MIs should be further investigated.
Abstract: OBJECTIVES: This study was designed to define the current role of multislice spiral computed tomography (MSCT) for the diagnosis of coronary artery disease (CAD) using a meta-analytic process. BACKGROUND: Multislice spiral computed tomography has recently been proposed as an alternative to conventional coronary angiography (CA) for the diagnosis of CAD. METHODS: Using Medline, we identified 29 studies (2,024 patients) evaluating CAD by means of both MSCT (> or =16 slices) and conventional CA before July 2006. After data extraction the analysis was performed according to a random-effects model. RESULTS: The per-segment analysis pooled the results from 27 studies corresponding to a cumulative number of 22,798 segments. Among unassessable segments, 4.2% were excluded from the analysis and 6.4% were classified at the discretion of the investigators, underscoring the shortcomings of MSCT. With this major limitation, the per-segment sensitivity and specificity were 81% (95% confidence interval [CI] 72% to 89%) and 93% (95% CI 90% to 97%), respectively, with positive and negative likelihood ratios of 21.5 (95% CI 13.1 to 35.5) and 0.11 (95% CI 0.06 to 0.21), respectively, and positive and negative predictive values of 67.8% (95% CI 57.6% to 78.0%) and 96.5% (95% CI 94.7% to 98.3%), respectively. As expected, the per-patient analysis has shown an increased sensitivity of 96% (95% CI 94% to 98%) but a decreased specificity of 74% (95% CI 65% to 84%). CONCLUSIONS: Multislice spiral computed tomography has shortcomings difficult to overcome in daily practice and, at the more clinically relevant per-patient analysis, continues to have moderate specificity in patients with high prevalence of CAD. Studies evaluating the diagnostic performance of the newest generation of MSCT, including patients with low to moderate CAD prevalence, will be critical in establishing the clinical role of this emerging technology as an alternative to CA.
Abstract: BACKGROUND: Antegrade femoral access is fraught by technical challenges and steeper learning curve, in comparison with retrograde contralateral femoral access. We appraised learning curve, complications, and technical aspects inherent in the adoption of antegrade approach. METHODS: Consecutive cases in which antegrade access was attempted by a cardiologist experienced in retrograde access, but inexperienced in antegrade, under supervision of an operator with anterograde expertise, were collected. The primary end-point was the occurrence of antegrade access failure or local complications. Major complications were defined as those life-threatening, requiring transfusion, percutaneous, or surgical repair. RESULTS: Anterograde access was attempted in 120 patients. The primary end-point occurred in 14 (11.6%) cases, but according to the learning curve, in 12 (20%) for first 60 cases vs 2 (3.3%) for the last 60 cases (P = 0.008). Access failure in the hands of the in-training operator was similarly found in all cases but one during the first 60 cases. No major complications occurred, while minor complications were found in 9 (7.5%) patients, again with all but two of them occurring in the first 60 cases. These included peri-adventitial extravasation in 8 patients (6.7%), and perforation of a small branch in one (0.8%); all these complications were conservatively and successfully managed. Obesity was the only significant predictor of access failure/complication (P = 0.004). CONCLUSIONS: This work, the first to report on the learning curve of the antegrade approach, supports the feasibility and safety of this access site even for an in-training operator, if supervised. A minimum caseload of 60 procedures is likely needed to master this technique.
Abstract: Arterial revascularization by means of percutaneous transluminal angioplasty (PTA) is a mainstay in the management of patients with peripheral artery disease and critical limb ischemia (CLI). While cross-over access from the contralateral femoral artery or antegrade access from the ipsilateral femoral artery are most commonly used when approaching subjects with CLI, PTA may occasionally fail when performed from these routes. We hereby report a patient in whom we performed retrograde arterial access through the posterior tibial artery, thus enabling recanalization of a challenging below-the-knee chronic total occlusion. Technical points pertinent to this case are clearly illustrated, including the sheathless approach and the use of a double wire strategy, one advanced ante-gradient and the other concomitantly advanced retro-gradient..
Abstract: OBJECTIVES: To describe a novel approach to drug-eluting stent (DES) implantation, the sandwich technique, comprised of the simultaneous implantation of two completely overlapping DES in the same target lesion. BACKGROUND: DES effectively prevent restenosis in selected coronary lesions. However, adverse lesion characteristics may detrimentally affect outcomes after DES implantation by means of plaque prolapse, recoil or excessive neointimal hyperplasia. METHODS: From July 2002 to November 2004, the sandwich technique was performed in 10 patients with very high-risk lesions. Two DES of identical size and length were implanted, one inside the other, with almost complete overlap. High-pressure postdilatation (up to 28 atm) was carried out in 6 cases. The endpoints of this preliminary evaluation were: technical feasibility, early (30-day) safety, restenosis rate and freedom from adverse events at 9-month follow up. RESULTS: Procedural and angiographic success was achieved in all cases. At follow-up, there were no deaths, myocardial infarctions or stent thromboses. All patients underwent angiographic follow-up; target lesion revascularization was carried out in 3 patients (30%). Of note, in no case was there evidence of aneurysmal remodeling. CONCLUSIONS: This study suggests that implanting 2 DES, one inside the other in a sandwich fashion, is feasible and apparently safe. This approach could be considered in situations such as plaque prolapse or stent recoil where additional scaffolding may be needed.
Abstract: OBJECTIVES: To assess the safety and efficacy of the AngioJet coronary device, given the uncertain risk-benefit balance of rheolytic thrombectomy in patients with acute myocardial infarction (AMI). BACKGROUND: Current risk of inadequate myocardial perfusion for thrombus embolization in primary coronary interventions is not negligible. The AngioJet thrombectomy device showed promising results in terms of safety and efficacy, but failed to confirm them in a large, multicenter, randomized trial, and the risk-benefit balance is still uncertain. METHODS: The AngioJet device was employed in 116 consecutive patients with AMI and angiographic evidence of extensive thrombosis in a vessel with a reference diameter > 2.5 mm. Stents and glycoprotein IIb/IIIa inhibitors were liberally used. Epicardial and myocardial reperfusion angiographic parameters, and in-hospital major adverse cardiac events (MACE, i.e., cardiac death, myocardial infarction, target vessel revascularization) were assessed. RESULTS: The AngioJet was successfully used in all patients. Angiographic analysis showed that the AngioJet significantly improved epicardial coronary flow (p < 0.01), frame count (p < 0.01) and myocardial blush (p < 0.01), while stenting yielded significant improvements only in diameter stenosis, minimum lesion diameter and correlated vessel parameters (p < 0.01). In-hospital MACE were uncommon [9 (8%)], despite the patientsO characteristics. When compared to an AMI population with similar thrombus burden but not undergoing thrombectomy, our AngioJet population showed significant improvement of reperfusion parameters. Moreover, there was greater AngioJet benefit in the high versus moderate thrombus burden subset; laboratory and operator experience also correlated significantly with final angiographic results. CONCLUSIONS: Our study supports the favorable risk-benefit profile of AngioJet device use in selected patients with AMI when used in experienced laboratories and by trained operators.
Abstract: BACKGROUND: In patients with acute coronary syndromes (ACS), distal embolization of thrombotic material is more likely to play a key role in the pathogenesis of myocardial no-reflow during percutaneous coronary intervention (PCI). Thus, interventional techniques able to reduce thrombus burden at the culprit vessel might improve final myocardial reperfusion. OBJECTIVE: To evaluate a new rapid-exchange thrombus-aspirating catheter, the Diver C.E., in patients with thrombotic coronary lesions undergoing PCI. METHODS: Fifty patients with acute myocardial infarction (n = 44) or with non-ST-elevation ACS and angiographic evidence of coronary thrombus (n = 6) undergoing urgent PCI were prospectively enrolled. The Diver C.E. was used to aspirate coronary thrombus from the culprit lesion after placement of the guidewire. Adjunctive balloon inflations and stent implantation were used to achieve good angiographic result. Angiographic coronary flow (by means of TIMI score and corrected TIMI frame count, cTFC), thrombus score (TS), and myocardial perfusion (by means of postintervention myocardial blush grade, MBG) were assessed in all patients. RESULTS: The device could be successfully employed in 96% of the cases (48/50) and yielded significant (P < 0.0001) acute reduction in thrombus burden (TS: predevice 3.5 +/- 0.8, postdevice 2.5 +/- 0.9) and improvement in coronary flow (TIMI grade: predevice 1.0 +/- 0.9, postdevice 2.0 +/- 0.9; CTFC predevice 71 +/- 31, postdevice 39 +/- 26). Final TIMI grade 0-1 was observed in one patient only (2%). A significant (P = 0.02) correlation was found between preintervention TS and efficacy of thrombus aspiration. A more pronounced acute reduction of thrombus burden after thrombus aspiration (TS reduction > or = 2) was associated with a better postintervention angiographic myocardial perfusion (MBG 2.3 +/- 0.9 vs 1.7 +/- 0.8; P = 0.05). CONCLUSIONS: This new, easy-to-use, device is able to reduce thrombus burden and to improve coronary flow in patients with thrombus-containing lesions. The improvement in myocardial perfusion associated to greater thrombus removal highlights the importance of thrombus aspiration in the management of thrombus-burdened coronary lesions.
Abstract: AIMS: The role of aspirin in patients with coronary artery disease (CAD) is well established, yet patients happen to discontinue aspirin according to physician's advice or unsupervised. We thus undertook a systematic review to appraise the hazards inherent to aspirin withdrawal or non-compliance in subjects at risk for or with CAD. METHODS AND RESULTS: Electronic databases were systematically searched (updated January 2006). Study designs, patient characteristics, and outcomes were abstracted. Pooled estimates for odds ratios (OR) were computed according to random-effect methods. From the 612 screened studies, six were selected (50,279 patients). One study (31,750 patients) focused on adherence to aspirin therapy in the secondary prevention of CAD, two studies (2594) on aspirin discontinuation in acute CAD, two studies (13,706) on adherence to aspirin therapy before or shortly after coronary artery bypass grafting, and another (2229) on aspirin discontinuation among patients undergoing drug-eluting stenting. Overall, aspirin non-adherence/withdrawal was associated with three-fold higher risk of major adverse cardiac events (OR=3.14 [1.75-5.61], P=0.0001). This risk was magnified in patients with intracoronary stents, as discontinuation of antiplatelet treatment was associated with an even higher risk of adverse events (OR=89.78 [29.90-269.60]). CONCLUSION: Non-compliance or withdrawal of aspirin treatment has ominous prognostic implication in subjects with or at moderate-to-high risk for CAD. Aspirin discontinuation in such patients should be advocated only when bleeding risk clearly overwhelms that of atherothrombotic events.
Abstract: OBJECTIVES: We sought to determine if the angiographic pattern of in-stent restenosis in drug-eluting stents (DES) maintains its prognostic importance. BACKGROUND: The pattern of restenosis in the bare-metal stent era had a significant impact on therapeutic outcomes. METHODS: We identified a total of 250 consecutive restenotic lesions in 203 patients (66.4% sirolimus-eluting stents and 33.6% paclitaxel-eluting stents). We divided these lesions into two groups: focal, defined as < or =10 mm, 163 lesions (65.2%); and nonfocal, which were diffuse, proliferative, or obstructive, 87 lesions (34.8%). The end points analyzed were angiographic restenosis and target lesion revascularization (TLR). RESULTS: Diabetes was the only clinical variable associated with the pattern of restenosis (28.8% focal compared with 52.9% diffuse; p = 0.0001). Angiographic follow-up of the treatment of restenosis was available in 61.2% of the lesions and was similar between the two groups. The rate of angiographic restenosis was 17.8% in the focal group and 51.1% in the nonfocal group (p = 0.0001). The incidence of TLR also increased with the type of restenosis treated (9.8% and 23%, respectively; p = 0.007). An adjusted multivariate analysis revealed that the pattern of restenosis remained associated with both the occurrence of restenosis and TLR (odds ratio [OR] 5.1 [95% confidence interval (CI) 1.1 to 23], p = 0.03; and OR 3.61 [95% CI 1.2 to 10.9], p = 0.02; respectively). CONCLUSIONS: Similar to bare-metal stent data, the angiographic pattern of restenosis following DES implantation is prognostically important. Diabetes is a significant predictor of the pattern of restenosis in the DES era.
Abstract: OBJECTIVES: To evaluate safety and efficacy of the CROSSER CTO Recanalization System (CROSSER). BACKGROUND: The CROSSER, a novel device dedicated to recanalization of chronic total occlusions (CTO), relies on a monorail catheter delivering vibrational energy to facilitate the crossing of occluded coronary arteries. METHODS: We included de novo or restenotic occlusions in native coronary arteries with typically unfavorable characteristics and a prior failed guidewire attempt either performed in a previous procedure or just before the usage of the CROSSER. The end points analyzed were technical success (ability to cross or facilitate a guidewire crossing into the true lumen), angiographic success (<20% residual stenosis and TIMI flow grade 3), and clinical success (angiographic success and freedom from major adverse cardiac events at 30 days). RESULTS: Twenty-eight patients (30 lesions) were included. The morphology was blunt in 83.3% and the length of the occlusion was >20 mm in 76.6%. The median age of the CTO was 9 months (range 3-60 months). Technical success was obtained in 19 (63%) occlusions and angiographic success in 16 (53%): 26.3% in lesions with prior procedural failure and 73.7% when CROSSER was attempted after initial guidewire failure. Complications were: one guidewire perforation without consequences and one peri-procedural myocardial infarction (MI). No events occurred within 30-day follow-up after discharge. CONCLUSIONS: In our experience, the CROSSER System is safe and increases the success of opening CTO refractory to guidewires. This novel device may represent an useful adjunct to the armamentarium of the interventional cardiologist.
Abstract: The burden of aortic stenosis is increasing steadily and, despite major advances in diagnosis and management, surgical valve replacement is still the only effective treatment. Most recently, experimental studies in animals and clinical studies in humans have shown that myocardial hypertrophy, microcirculatory dysfunction and cardiomyocyte apoptosis are among the central pathophysiologic mechanisms involved in the natural history of aortic stenosis, i.e. the passage from a compensated and hypertrophic heart to a dysfunctional heart prone to ischemia, arrhythmia and pump failure. This updated review emphasizes the promises of these new research avenues as well as their potential therapeutic applications.
Abstract: BACKGROUND: Elective intraaortic balloon pump (IABP) may reduce acute complications during unprotected left main (ULM) stenting. However, few data exist on criteria for elective IABP support during ULM stenting. METHODS: Since January 1993, 219 consecutive patients underwent elective ULM stenting: 69 had elective IABP support (elective IABP group), whereas 150 patients had conventional procedure (conservative group). Criteria for elective IABP support were (1) lesion located in the distal segment of the left main (bifurcation lesion), (2) left ventricular ejection fraction <40%, (3) atherectomy, (4) unstable angina, and (5) critical disease of the right coronary artery. Incidence of intraprocedural major adverse cardiac events (eg, severe hypotension and/or shock, myocardial infarction, urgent bypass surgery, and death) was assessed. RESULTS: Euroscore >6 (identifying high-risk patients) occurred in 38% in the elective IABP group and 13% in the conservative group (P < .001). Severe hemodynamic instability occurred in 12 patients (8%) in the conservative group and in none in the elective IABP group (P = .020). Intraprocedural major adverse cardiac event was higher in the conservative group (9.5% vs 1.5%, P = .032). Elective IABP support (OR 0.08, 95% CI 0.01-0.69, P = .022) and presence of Euroscore >6 plus bifurcation lesion (OR 5.49; 95% CI 1.47-20.51; P = .011) were the independent predictors of intraprocedural events. CONCLUSIONS: Elective IABP may prevent intraprocedural events in elective ULM stenting, especially in patients at higher risk.
Abstract: AIM: To evaluate patterns of restenosis following implantation of sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) in comparable unselected lesions. METHODS AND RESULTS: We have identified all episodes of restenosis after SES or PES implantation in our institutions between March 2003 and March 2005. Restenosis pattern was classified as focal, diffuse, proliferative, or occlusive. The position of focal restenosis was also categorized as proximal, in-stent, distal, or multi-focal. We have characterized 150 and 149 restenotic lesions in SES and PES groups, respectively. The incidence of diffuse and occlusive restenosis was significantly higher in PES than in SES (47.6 vs. 27.0%, P < 0.001). Multivariable (OR 2.693, 95% CI 1.425-5.089, P = 0.002) and propensity (OR 3.00, 95% CI 1.584-5.672, P < 0.001) analyses confirmed the positive association of PES with non-focal restenosis. For both stents, focal-edge restenosis was significantly more likely to occur proximally than distally (61.0 vs. 16.9%, P < 0.001 for PES and 45.8 vs. 16.8%, P < 0.001 for SES). CONCLUSION: Focal restenosis remains the most common pattern with SES. In contrast, just under half of restenosis in PES is the more severe non-focal pattern. Paradoxically, the majority of focal restenosis occurs at the proximal stent margin for both platforms.
Abstract: AIMS: To systematically assess the risk/benefit ratio of a rate-control strategy vs. a rhythm-control strategy in patients with first or recurrent atrial fibrillation (AF). METHODS AND RESULTS: We searched Medline, CENTRAL, and other sources up to September 2004 for randomized trials. Individual and pooled random-effect odd ratios (OR) and 95% confidence intervals (CI) [OR (95% CI)] were calculated for the combined endpoint of all cause death and thromboembolic stroke (CEP), major bleeds (intra and extracranial), and systemic embolism. Number needed to treat (NNT) to avoid one CEP and heterogeneity were also assessed. Five studies enrolling 5239 patients with AF compared rate-control vs. rhythm-control. Average follow-up ranged from 1 to 3.5 years. A rate-control strategy compared with a rhythm-control approach was associated with a significantly reduced risk of CEP [OR 0.84 (0.73, 0.98), P=0.02], and with a trend towards a reduced risk of death [OR 0.87 (0.74, 1.02), P=0.09] and thromboembolic stroke [OR 0.80 (0.6, 1.07), P=0.14]. NNT to save one CEP was 50. There was no significant difference in the risk of major bleeds [OR 1.14 (0.9, 1.45), P=0.28] and systemic embolism [OR 0.93 (0.43, 2.02), P=0.90]. No significant heterogeneity was found in any of the analyses (P>0.1). CONCLUSION: This meta-analysis of 5239 patients with AF indicates that an initial rate-control strategy compared with a rhythm-control one is associated with a better prognosis, thus representing the standard treatment against which to test new therapeutic approaches.
Abstract: The buddy wire technique, i.e. the use of a second 0.014 inch guide wire placed alongside the one employed to advance balloons and stents inside the coronary artery during percutaneous coronary intervention (PCI), may help in a series of procedural challenges during PCI. Indeed, by improving both the stability of the guiding catheter and the support for balloon and stent, a buddy wire use is sometimes the simplest way to accomplish a successful procedure. In this paper, we discuss technical aspects of some specific circumstances frequently encountered during PCI, in which a buddy wire may be helpful. These include: 1) The reduction of balloon slippage during angioplasty for in-stent restenosis; 2) insufficient back-up of the guiding catheter; 3) stenting of lesions located in vessels with proximal tortuosities/angulations; 4) stenting of lesions distally located in the vessel; 5) facilitation in the positioning of distal protection devices; 6) stenting of a lesion distally located from a previously implanted stent or from a coronary segment with both calcification and sharp bend; 7) PCI on coronary arteries with anomalous origin. Because of its simplicity, low cost, and availability, the use of a buddy wire should be considered when dealing with the aforementioned conditions during PCI procedures.
Abstract: BACKGROUND: Although recent data support an early invasive management in acute coronary syndromes (ACS), overall evidence appears conflicting. We performed a metaregression to explore the impact of intracoronary stenting and aggressive antiplatelet treatment on the risk/benefit ratio of an early invasive approach. METHODS: We searched several databases up to March 2004 for randomized trials comparing an early invasive versus delayed invasive or conservative management in ACS. Random-effects odds ratios were computed for death and/or myocardial infarction at the longest follow-up. Log (odds ratios) were tested for interaction with stenting and aggressive antiplatelet treatment (ie, glycoprotein IIb/IIIa inhibitors or thienopyridines in addition to aspirin). RESULTS: Ten trials (9990 patients, median follow-up 12 months) were pooled. Overall, an early invasive management was associated with significantly reduced rates of death or myocardial infarction (P = .01). Metaregression analysis showed that the 2 most significant predictors of the benefits of an early invasive strategy in patients with ACS on event-free survival were the use, in subjects managed invasively, of aggressive antiplatelet treatment (P = .005) and stenting (P = .011). Moreover, both stenting and aggressive antiplatelet treatment were significantly associated with reduced mortality (respectively, P = .014 and P = .009) and correlated to each other (r = 0.76, P = .010). CONCLUSIONS: This study shows that the benefits of an early invasive approach in patients with ACS are significantly associated with concomitant aggressive antiplatelet treatment and stenting. These findings thus suggest the overall superiority of an early invasive approach in ACS, as long as state-of-the-art therapies are implemented.
Abstract: Reversible vascular obstructive lesions, i.e. pseudostenoses, may pose significant threats to interventional cardiologists as they can be mistaken for obstructive lesions and prompt inappropriate revascularization procedures. We hereby report for the first time in the literature a case of external iliac artery pseudostenosis due to catheter straightening of significant underlying vessel tortuosities. Despite the initial angiographic image obtained from retrograde catheterization of the right external iliac artery which was strongly suggestive for significant stenosis, a thorough review of clinical history, physical examination and a second-look angiography by means of contralateral catheterization and contrast injection showed the absence of any significant lesion in the tortuous left external iliac artery, thus avoiding an unnecessary and potentially harmful vascular intervention. This clinical vignette emphasizes the importance of a thorough clinical examination and angiographic assessment for the appropriate diagnosis and management of reversible stenoses.
Abstract: Patients with severe calcific aortic stenosis are occasionally not amenable to surgery because of advanced age or severe co-morbidities. Percutaneous aortic valve dilation is used but has only limited time relief. While preclinical evidence on percutaneous aortic valve replacement seems promising, only very limited clinical data are available worldwide. We hereby present the first case of percutaneous aortic valve replacement successfully performed in Italy in a 74-year-old high-risk female. This case emphasizes the technical challenges inherent to this procedure and its promising role in selected very high-risk patients with severe aortic stenosis, notwithstanding the early and long-term risk of adverse events.
Abstract: We report hypoxia-inducible factor-1 (HIF-1) expression in myocardium of patients with recent acute myocardial infarction (AMI), supporting the hypothesis of HIF-1 as a possible mediator of response to ischemia. A potential diagnostic role of determining tissue expression of HIF-1 as a marker of ischemia, and potential therapeutic implications by trying to modulate HIF-1 activity in order to promote beneficial effects of HIF-1 related genes (e.g. expression of vascular endothelial growth factor (VEGF)) may derive.
Abstract: Coronary artery anomalies (CAA) often render technically difficult the completion of coronary angiography and intervention. Their presence in patients undergoing emergency angiography for acute myocardial infarction (AMI) is particularly challenging for interventional cardiologists. In this article, we report, for the first time in the literature, a case of rescue percutaneous coronary intervention for failed thrombolysis in a patient with AMI due to occlusion of a left circumflex coronary artery with anomalous origin from right sinus of Valsalva (in an anomalous left coronary system also including an anomalous origin of the left anterior descending artery from the right sinus). In particular, the present clinical vignette emphasizes the importance of a thorough search for the culprit vessel during cardiac catheterization. Especially in the emergency setting, non-invasive methods of ischemia localization, such as ST-segment elevation at the ECG and wall motion abnormalities at echocardiography, are of pivotal usefulness to guide the interventional cardiologist in identifying and treating the diseased coronary vessel in a timely and effective fashion.
Abstract: AIMS: Drug-eluting stents (DES) have been recently investigated, with favorable data for many devices, but comparative data are lacking. We thus performed an adjusted indirect comparison metaanalysis of DES. METHODS: Randomized trials comparing DES vs. bare-metal stents (BMS) were systematically searched, and random effect odds ratios (OR) were computed for target lesion revascularization (TLR) and binary in-stent restenosis rate (BRR) at 6-12 months. We then generated interaction OR for the comparison of different DES. RESULTS: We pooled data from 17 studies (allocating 3048 patients to BMS and 3392 to nine different DES). Indirect head-to-head comparison of sirolimus-eluting Cypher (N=1007) vs. polymeric paclitaxel-eluting Taxus (N=959) showed nonsignificant differences in TLR [OR=0.8 (0.5-1.4), p=0.45] but significant reductions in BRR favoring Cypher [OR=0.3 (0.1-0.6), p<0.001]. Everolimus-eluting stents appeared noninferior to Cypher or Taxus (p>0.50 for both TLR and BRR). Actinomycin-, mycophenolate-, and apolymeric paclitaxel-eluting stents (PES) all proved significantly worse than Cypher or Taxus for TLR or BRR. CONCLUSION: Notwithstanding its inherent limitations, the present metaanalysis confirms the effectiveness of both Cypher and Taxus, supports the promising role of everolimus-eluting stents, and suggests the significant inferiority of most other devices. These post hoc findings, albeit intriguing, await prospective confirmation.
Abstract: AIMS: To compare, by meta-analytical techniques, the clinical impact of bare-metal stenting vs. balloon angioplasty for the treatment of lesions in small coronary arteries. METHODS AND RESULTS: We included trials with random allocation and prospective comparison of angioplasty vs. stenting, reference vessel diameter<3 mm, and follow-up>or=6 months. Random effect odds ratios (OR) for death, myocardial infarction (MI), repeat revascularization (RR), and major adverse cardiac events (MACEs) were computed. In a pre-specified subgroup analysis, we compared stenting with optimal (post-procedural stenosis<20%) and suboptimal (>20%) angioplasty. Thirteen studies (4383 patients) were selected. No differences were found in terms of death and MI, while MACEs, mainly driven by RR, were significantly less common after stenting (17.6%) than after angioplasty (22.7%), OR 0.71 (0.57-0.90). Heterogeneity among trials was present. When considering only optimal angioplasty, MACE rates were homogeneously similar, 17.9 vs. 21.1%, OR 0.86 (0.66-1.11). If angioplasty were suboptimal, MACEs were significantly more common after angioplasty (24%) than after stenting (17.3%), OR 0.62 (0.44-0.88). CONCLUSION: Stenting is superior to balloon angioplasty for the treatment of small vessels, in particular after suboptimal angioplasty. However, MACE and RR rates remain high after stenting, and the advantage of stent over angioplasty is moderate. An optimal balloon angioplasty strategy (with provisional stenting) may achieve results not inferior to routine stenting.
Abstract: In this study we randomly compared the estradiol eluting stent (17-beta-E) with phosphorylcholine (PC)-coated stents in native coronary arteries. The incidence of angiographic restenosis was 23% in the 17-beta-E group and 31% in the PC group (p = 0.34). The major adverse cardiovascular event rates were also similar in the 2 groups (17% in the 17-beta-E group vs 22% in the PC group, p = 0.47). The mid-term clinical and angiographic outcomes did not indicate superiority of the 17-beta-E eluting stent over the control PC stent.
Abstract: BACKGROUND: Recent data suggest that the intracoronary (i.c.) administration of a systemic bolus dose of abciximab during PCI may increase the efficacy of this antiplatelet drug. However, the effect of i.c. abciximab on coronary angiographic flow has been not clarified. METHODS: We studied 37 consecutive patients with acute coronary syndromes (ACS) who underwent successful urgent PCI on the target vessel and were treated by an i.c. abciximab bolus (0.25 mg/kg) prior to the first balloon inflation (Group IC), and 37 matched controls who were treated by intravenous (i.v.) abciximab bolus at the same dose (Group IV). Corrected TIMI frame count (CTFC) in the culprit and in a non-culprit coronary artery branch was assessed before treatment, immediately after intracoronary administration of abciximab bolus and at the end of the procedure. RESULTS: After administration of abciximab, CTFC significantly decreased from 48+37 to 33+30 (P=0.001) in the culprit vessel while in the non-culprit vessel it remained unchanged (16+7 pre-treatment and 16+7 post-treatment, P=0.68). Final CTFC was 12+4 in Group IC and 14+5 in Group IV (P=0.069). Post-treatment mean peak of the cardiac enzymes showed a trend toward reduction in Group IC compared with Group IV. CONCLUSIONS: The i.c. administration of abciximab bolus acutely decreases CTFC through culprit vessels of patients with ACS undergoing urgent PCI. Further studies evaluating the potential clinical benefits associated with i.c. abciximab administration are warranted.
Abstract: We compared the clinical efficacy of paclitaxel-eluting stents (PESs) and sirolimus-eluting stents (SESs) in a contemporary cohort of patients who had complex lesions. We collected data on 9-month outcomes in 529 patients (281 in the PES group and 248 in the SES group) whose de novo lesions were treated with drug-eluting stents. The end point was per-patient in-hospital and follow-up major adverse cardiac events, which were defined as a composite of death, myocardial infarction, and target vessel revascularization, including target lesion revascularization. There were no in-hospital deaths or repeat revascularizations; however, 5.7% of the PES group and 2% of the SES group developed a myocardial infarction (p = 0.04). At a median follow-up of 10.6 months, the rate of major adverse cardiac events was similar between groups (18.1% vs 21%, adjusted hazard ratio 0.85, 95% confidence interval 0.57 to 1.25), without any difference in the occurrence of death or myocardial infarction. Diabetes and total stent length were independent predictors of major adverse cardiac events. Propensity analysis confirmed the similarity between devices (hazard ratio 0.87, 95% confidence interval 0.62 to 1.25). Most restenoses were focal and only 2 patients required surgical revascularization. In conclusion, implantation of drug-eluting stents in complex lesions was associated with favorable results and most patients remained free from surgical revascularization at follow-up. Overall, the 2 available stent platforms had similar performance characteristics.
Abstract: Patients with myasthenia gravis undergo lifelong treatment with anticholinesterase agents. While the heart is usually unaffected by this disease, clinicians should bear in mind the potential adverse interaction between cardiac function and the underlying myasthenic disease or its specific medications. In the present article we report, to the best of our knowledge for the first time in the literature, a case of vasospastic acute myocardial infarction due to iatrogenic hypercholinergic crisis secondary to anticholinesterase therapy in an elderly female with myasthenia gravis. This clinical vignette emphasizes the importance of taking into account the potential vasospastic effect of anticholinesterase drugs. Indeed, prompt recognition of the pathophysiology of myocardial ischemia due to iatrogenic hypercholinergic crisis is pivotal to the timely and appropriate management of this medical emergency, as well as prevention of future recurrences.
Abstract: We report an unusual suicide, committed with a common pencil. A 72-year-old male inflicted himself a penetrating thoracic wound while being hospitalized for a hip prosthesis operation. Although the patient was immediately operated, the cardiac injury appeared to be fatal. Cases of suicidal penetrating wounds of the anterior chest wall are rare and they are mostly inflicted by knives, glass fragments, or other sharp instruments. The potential danger of a pencil should be taken into consideration, especially in psychiatric hospitals and imprisonment facilities. We examined the legislation in Italy and Finland concerning the regulation of privacy in special care institutions.
Abstract: AIMS: Unfavourable cardiac remodelling often complicates acute myocardial infarction (AMI) as a result of increased cardiomyocyte apoptosis. It is currently unclear whether ongoing or recurrent ischaemia is an independent determinant for increased apoptosis in peri-infarct viable myocardium. METHODS AND RESULTS: In order to assess the link between infarct-related artery (IRA) occlusion, ischaemia, and apoptosis, 30 subjects dying 7-120 days after AMI (16 with IRA occlusion and 14 with patent IRA) and five control subjects were selected at autopsy. Cardiomyocytes were defined as apoptotic if co-expressing TUNEL and activated caspase-3. Expression of both hypoxia-inducible factor-1 and cyclo-oxygenase-2 was assessed in the peri-infarct myocardium and considered as tissue markers of ischaemia. Evidence of ischaemia was significantly more frequent in cases with IRA occlusion (53%) than in cases with patent IRA (15%) or control hearts (0%, P=0.026). The finding of IRA occlusion and markers of ischaemia identified cases with higher apoptotic rates (ARs) in the peri-infarct viable myocardium [12.2% (8.2-14.0), P<0.001 vs. others], whereas IRA occlusion without ischaemia was associated with lower AR, not significantly different from patent IRA [3.0% (1.0-7.9) vs. 2.2% (1.0-5.8), respectively, P=0.42] CONCLUSION: Ischaemia in the peri-infarct viable myocardium is present in over 50% of subjects dying late after AMI with IRA occlusion, and it is associated with increased apoptosis. Relief of ischaemia after AMI may prove of benefit in preventing apoptosis and its consequences.
Abstract: Although predictors of acute intraprocedural stent thrombosis (IPST) in the drug-eluting stent era have been proposed, external validation is lacking. We thus analyzed the occurrence of IPST in the RECIPE study and found that, among 1,320 patients who underwent drug-eluting stent implantation, IPST occurred in 6 (0.5%), with in-hospital major adverse events in 4 (67%). IPST was predicted by number and total length of implanted stents, baseline minimal lumen diameter, and, in a pooled analysis that incorporated values from the present study and a previous study, use of elective glycoprotein IIb/IIIa inhibitors. Such results may provide useful information to guide prevention of this complication.
Abstract: Gadolinium chelates have been recently proposed and preliminarily tested as contrast agents for diagnostic and interventional angiography in alternative to iodinated media. However, in most studies low-osmolarity agents were employed and digital subtraction was required for satisfactory images. In this article, we report for the first time in the literature two cases of successful percutaneous renal artery stenting in which gadobutrol, a high-osmolar (1 mmol/ml) gadolinium chelate, was employed as contrast agent because of chronic renal failure and substantial risk for iodinated contrast-associated nephrotoxicity. In both patients gadobutrol yielded high-quality images without digital subtraction and was well tolerated with no ensuing renal dysfunction.
Abstract: OBJECTIVES: The aim of this study was to evaluate the use of a new manual thrombus-aspirating device in unselected patients with ST-segment elevation acute myocardial infarction (STEMI) undergoing urgent percutaneous coronary intervention (PCI). BACKGROUND: Failure to achieve myocardial reperfusion often occurs during PCI in patients with STEMI. The use of thrombus-aspirating devices might improve myocardial reperfusion by reducing distal embolization. METHODS: We prospectively randomized before coronary angiography 100 consecutive patients with STEMI to either standard PCI or PCI with manual thrombus-aspiration. Primary end points of the study were post-procedural rates of myocardial blush grade (MBG) > or =2 and ST-segment resolution (STR) > or =70%. Analyses were planned by intention to treat. RESULTS: Ninety-nine patients entered the analyses. The rates of post-procedural MBG > or =2 and STR > or =70% were, respectively, 68.0% and 44.9% in the thrombus-aspiration group compared with 58.0% and 36.7% in the standard PCI group: odds ratio (OR) 2.6 (95% confidence interval [CI] 1.2 to 5.9), p = 0.020, and 2.4 (95% CI 1.1 to 5.3), p = 0.034, respectively. Moreover, the rate of patients achieving both the angiographic and electrocardiographic (ECG) criteria of optimal reperfusion was significantly higher in the thrombus-aspiration group compared with standard PCI: 46.0% versus 24.5%, OR 2.6 (95% CI 1.1 to 6.2), p = 0.025. In multivariate analysis, randomization to thrombus-aspiration was a significant independent predictor of achievement of MBG > or =2 and STR > or =70% (p = 0.013). CONCLUSIONS: This prospective randomized study shows that manual thrombus-aspiration in unselected patients with STEMI undergoing primary or rescue PCI is clinically feasible and results in better angiographic and ECG myocardial reperfusion rates compared with those achieved by standard PCI.
Abstract: Intravascular ultrasound (IVUS) has provided in the last 2 decades major insights into the pathophysiology of coronary artery disease, and the mechanisms of action of percutaneous revascularization devices, helping the widespread adoption of coronary stents. The introduction of drug-eluting stents (DES) has recently lead to a revolution in the field of interventional cardiology, by virtually eliminating restenosis in selected low-risk lesions and significantly reducing both restenosis and repeat revascularizations in higher risk lesions. At the moment, the role of IVUS in the DES era is not well defined. Clinical studies utilizing IVUS in DES implantation used this technology mainly to evaluate the endpoint of intimal hyperplasia and to study the problem of incomplete apposition. On a theoretical basis, a method able to better evaluate optimal placement of a local drug delivery system should have a high rationale. Despite this sound preamble, no specific investigation has been conducted to evaluate the clinical need and possible advantage of routine IVUS for DES implantation and uncertainty is still present. A major hindrance lays in the low incidence of restenosis in most randomized trials enrolling few selected lesions per patient, as this fact enlarges the number of patients who need to be treated to demonstrate a benefit and casts doubts on the cost effectiveness of a more expensive and time consuming approach. The situation is bound to change when more complex patients and lesions are being treated, a setting associated with a higher event rate even when DES are used. While waiting for a prospective study addressing such issue, we can only rely on indirect evidence to justify and support the usage of IVUS in complex clinical settings with implantation of DES.
Abstract: AIM: Clopidogrel is an established alternative to ticlopidine in addition to aspirin after coronary stenting because of its hematologic safety, but its efficacy in comparison to ticlopidine is debated. We thus systematically reviewed randomized trials comparing clopidogrel vs ticlopidine after coronary stenting. METHODS: Medline (1/1986-10/2003), BioMed Central, Central, Current Contents, LILACS and mRCT were searched. Fixed-effect relative risks (RR [95% CI]) were computed, and the primary end-point was death. Heterogeneity tests and subgroup analyses were performed according to loading vs non-loading clopidogrel scheme. RESULTS: Five trials were retrieved (2 962 patients, average follow-up 7.4 months). In 3 studies both clopidogrel and ticlopidine were started with a loading dose, in 1 trial clopidogrel was administered without loading, and in 1 trial clopidogrel could be administered with or without loading. Overall analysis (p for heterogeneity=0.12) showed a non-significant trend toward increased mortality in patients treated with clopidogrel (38/1 649 [2.3%]) vs ticlopidine (22/1 313 [1.7%], RR=1.64 [0.94-2.86], p=0.080). After stratification, clopidogrel with loading was associated with non-significantly lower mortality rates than ticlopidine (9/959 [0.9%] vs 13/798 [1.6%], RR=0.68 [0.29-1.63], p=0.39). Instead, clopidogrel without any loading yielded a highly significantly 3-fold increased risk of death than ticlopidine (29/690 [4.2%] vs 9/515 [1.7%], RR=2.9 [1.45-6.1], p=0.0029). Similar results were obtained for the rate of death or non-fatal myocardial infarction. CONCLUSION: This meta-analysis suggests that clopidogrel treatment including a loading regimen is equivalent or may even be superior to ticlopidine after coronary stenting. However, current evidence shows conversely that clopidogrel therapy in the absence of a loading dose is associated with a significantly higher risk of death or myocardial infarction.
Abstract: BACKGROUND: Diffuse coronary vascular inflammation is associated with acute coronary syndromes. However, it is unknown whether inflammation also occurs within the myocardium. Therefore, this study was aimed at assessing the presence of activated cells in unaffected remote myocardium of patients with acute myocardial infarction (AMI), in comparison to the peri-infarct region from the same cases, and in comparison to myocardial specimens from control hearts. METHODS AND RESULTS: Sixteen patients dying 1 to 12 weeks after AMI and 16 control subjects were selected at autopsy. Myocardial specimens were taken at remote unaffected viable regions and at peri-infarct regions in cases with AMI. Confocal microscopy was performed to measure the number of activated cells (DR+), T-lymphocytes (CD3+), and activated T-lymphocytes (CD3+/DR+). Activated cells and activated T-lymphocytes were found in remote unaffected regions in 11 of 16 cases (69%), in peri-infarct zone in all cases (100%), and in none of the control hearts (0%, P<0.001 versus others). A greater myocardial inflammatory burden in remote regions but not in peri-infarct regions was associated with persistent infarct-related artery occlusion (P<0.05). CONCLUSIONS: This study for the first time shows the presence of activated T-lymphocytes in remote unaffected myocardial regions in approximately two thirds of patients with recent AMI. Because these cells are associated with persistent infarct-related artery occlusion, our data may suggest that an antigenic stimulus present also in the myocardium triggers an immune response that may be critical to precipitate artery occlusion.
Abstract: Coronary artery aneurysms are rare findings usually diagnosed incidentally at necropsy or at angiography in patients with symptoms of myocardial ischaemia. Even if atherosclerosis is a common cause of coronary aneurysms in the adult, other acquired diseases with inflammatory pathogenesis are associated with coronary artery aneurysms. We present three cases of patients with low probability of coronary artery atherosclerotic disease, due to their age, risk factors profile and history, complaining of chest pain suggestive of myocardial ischaemia and angiographic documentation of one or more coronary aneurysms. In all cases, although no patient had had a previous diagnosis of Kawasaki disease (KD), an unexplained febrile syndrome had occurred in childhood, which is compatible with misdiagnosed episode of KD causing the aneurysmatic lesions. The present reports highlight the potential clinical relevance of previously misdiagnosed KD in patients with ischaemic chest pain, low probability of atherosclerosis and coronary aneurysms.
Abstract: BACKGROUND: Multivessel coronary disease after myocardial infarction is a major risk factor for unfavorable cardiac remodeling and death due to pump failure, but underlying pathophysiologic mechanisms are still uncompletely established. Post-infarction myocardial apoptosis has been recently implicated as a cause of ongoing cell loss leading to cardiac failure. Our aim was to assess the role of post-infarction myocardial apoptosis and pro-apoptotic factor expression in the non-infarcted remote myocardium of subjects with multivessel coronary disease. METHODS: Twenty-one males dying after recent myocardial infarction with permanent occlusion of the infarct-related artery were selected at autopsy. Apoptosis was assessed at viable myocardial regions remote from infarction by co-staining for in situ end-labeling of DNA fragmentation and cleaved caspase-3. Expression of pro-apoptotic factor bax and hypoxia-induced factor-1alpha was evaluated by immunohistochemistry. RESULTS: Subjects with multivessel disease (N=11) showed a significantly two-fold higher myocardial apoptosis in comparison to subjects with single vessel disease (N=10) (0.9% vs. 0.5%, p=0.013). Similarly, myocardial bax expression was increased in patients with multivessel disease (3.0% vs. 1.4%, p=0.029). Stratification for the number of diseased coronary vessels confirmed the association between extent of coronary disease and apoptotic rates (p=0.022). Even in subjects dying over 30 days after infarction multivessel disease remained predictive of enhanced myocardiocyte apoptosis at remote regions (p=0.033). CONCLUSIONS: Post-infarction myocardial apoptosis and bax expression in remote left ventricular regions are significantly increased in male patients with multivessel coronary disease in comparison to those with isolated infarct-related artery occlusion. These findings suggest that apoptotic cell loss in the viable non-infarcted myocardium, possibly due ongoing ischemia, may play a relevant role in the unfavorable clinical course typical of multivessel disease after myocardial infarction.
Abstract: OBJECTIVES: We sought to compare, through a meta-analytic process, the transradial and transfemoral approaches for coronary procedures in terms of clinical and procedural outcomes. BACKGROUND: The radial approach has been increasingly used as an alternative to femoral access. Several trials have compared these two approaches, with inconclusive results. METHODS: The MEDLINE, CENTRAL, and conference proceedings from major cardiologic associations were searched. Random-effect odds ratios (ORs) for failure of the procedure (crossover to different entry site or impossibility to perform the planned procedure), entry site complications (major hematoma, vascular surgery, or arteriovenous fistula), and major adverse cardiovascular events (MACE), defined as death, myocardial infarction, emergency revascularization, or stroke, were computed. RESULTS: Twelve randomized trials (n = 3,224) were included in the analysis. The risk of MACE was similar for the radial versus femoral approach (OR 0.92, 95% confidence interval [CI] 0.57 to 1.48; p = 0.7). Instead, radial access was associated with a significantly lower rate of entry site complications (OR 0.20, 95% CI 0.09 to 0.42; p < 0.0001), even if at the price of a higher rate of procedural failure (OR 3.30, 95% CI 1.63 to 6.71; p < 0.001). CONCLUSIONS: The radial approach for coronary procedures appears as a safe alternative to femoral access. Moreover, radial access virtually eliminates local vascular complications, thanks to a time-sparing hemostasis technique. However, gaining radial access requires higher technical skills, thus yielding an overall lower success rate. Nonetheless, a clear ongoing trend toward equalization of the two procedures, in terms of procedural success, is evident through the years, probably due to technologic progress of materials and increased operator experience.
Abstract: Cardiac surgery (CS), in particular cardiopulmonary bypass and cardioplegia, have been reported to trigger myocardial inflammation and apoptosis. This surgery-related inflammatory reaction appears to be of extreme complexity with regard to its molecular, cellular and tissue mechanisms. Both experimental and clinical studies have ascertained the role of several hormonal mediators, mitochondria, cardioplegia and extracorporeal circulation temperature, apoptosis and even genetic modulators of damage. However, the correlations between these factors in vivo and post-surgery outcome and prognosis have not yet been systematically investigated. In animal models of myocardial cardioplegia and/or ischemia-reperfusion, experimental drugs such as antioxidants have been documented to provide amelioration of post-intervention cardiac performance and reduction of apoptosis suggesting the possibility of new therapeutic strategies. However, these findings have been only partially confirmed in humans. Moreover, markers for the differential detection of early and late phases of apoptosis are subjects of intense investigations. This review will provide an overview of the major studies about the link between ischemia, myocardial inflammation and apoptosis during and after CS, with particular regard to the markers and methods for apoptosis detection.
Abstract: BACKGROUND: Cyclo-oxygenase-2 (COX-2) is induced in cardiomyocytes only in response to stress, such as ischaemia. OBJECTIVE: To assess COX-2 expression at the site of recent myocardial infarction. METHODS: COX-2 expression was evaluated by specific immunostaining in cardiomyocytes from 23 subjects who died 10-60 days after acute myocardial infarction. The relation between COX-2 myocardial expression and apoptotic rate was investigated. Cardiomyocyte apoptotic rate was defined as the number of cells co-expressing in situ end labelling of DNA fragmentation (TUNEL) and immunostaining for activated caspase-3. RESULTS: COX-2 expression was found in cardiomyocytes at the site of infarction in nine of 23 cases (39%). It was associated with fivefold higher apoptotic rates (median 17.9% (interquartile range 11.0-25.4%) v 3.7% (0.6-12.8%); p = 0.016), and apoptotic rate increased progressively from mild to intense COX-2 staining (p for trend 0.009). COX-2 expression co-localised with TUNEL nuclear staining in myocytes, and there was a high concordance between COX-2 and hypoxia induced factor 1-alpha staining (78%, p = 0.021) and between COX-2 and bax (83%, p = 0.014). Subjects showing myocardial COX-2 expression were more likely to have enlarged hearts (p = 0.050), and intense COX-2 staining was strictly associated with symptomatic heart failure (p = 0.035). CONCLUSIONS: COX-2 is expressed in cardiomyocytes in nearly 40% of cases at the site of recent acute myocardial infarction, even late after the index event. Its expression was associated with extremely high apoptotic rates. These findings suggest a potential cause-effect link between COX-2 expression and enhanced myocardial apoptosis in ischaemic cardiomyopathy.
Abstract: Heart failure appears to be less common and less severe in females, and elderly women have a better overall survival after myocardial infarction than males and also a decreased risk of arrhythmic death. Human and animal studies also show that females display more favorable cardiac remodeling in several experimental and clinical conditions. However, the underlying pathophysiologic mechanisms have not been established, even though estrogens, beta-adrenergic stimulation, the renin-angiotensin system, and a greater resistance to myocardiocyte apoptosis in females have been proposed as hypothetical contributing factors. Indeed, epidemiologic, experimental and clinical evidence of gender differences in myocardial remodeling and heart failure favoring women could prompt the use of female myocardial progenitor or stem cells for cellular replacement therapy in cardiac failure, on the premises of a greater protection from myocardial apoptosis and unfavorable remodeling in women.
Abstract: BACKGROUND: Apoptosis is a key feature in postinfarction remodelling leading to progressive myocyte loss. Both proapoptotic and antiapoptotic factors contribute to the delicate balance between death and survival. The survivin pathway has emerged as essential in the control of apoptosis, although its role in heart disease is unknown.AIM: To evaluate survivin expression after acute myocardial infarction (AMI). METHODS: Survivin expression was assessed immunohistochemically in the peri-infarct and remote viable myocardium in 17 consecutive patients who died 1-30 weeks after AMI and in four control hearts. RESULTS: Survivin was expressed by myocytes in the peri-infarct area in eight patients and in the remote region in 13 patients. The rate of survivin expression after AMI was significantly higher in the remote versus peri-infarct regions and compared with control hearts. Its expression was inversely associated with the presence of dilated cardiopathy and of apoptosis, independently from the gross pathology infarct size. CONCLUSIONS: Survivin myocardial expression after AMI may be associated with the survival of at risk myocardium and may be indicative of more favourable remodelling after AMI. These findings identify a potential new target for the treatment of postinfarction remodelling.
Abstract: BACKGROUND: Cardiac remodelling after acute myocardial infarction (AMI) is characterised by molecular and cellular mechanisms involving both left and right ventricles, and biventricular failure identifies patients with an extremely unfavourable prognosis. AIMS: To assess whether a link exists between increased myocardial apoptotic rates (AR) at sites of recent infarction and patterns of unfavourable cardiac remodelling, such as biventricular enlargement after left ventricular (LV) infarction. METHODS: Twelve patients with recent AMI involving the LV and not the right ventricle (RV) and with permanent infarct related artery occlusion were selected at necropsy. Gross pathological characteristics, such as LV and RV dilatation, and AR at site of infarction were assessed. Potential false positive results (DNA synthesis and RNA splicing) were excluded from the cell count. RESULTS: RV enlargement, defined as a tricuspidal ring greater than 120 mm, was found in five cases and was associated with LV dilatation. These patients showed significantly higher AR than the others. When the subjects were divided into three groups according to progressive cardiac remodelling (absence of cardiac dilatation, isolated LV dilatation, and biventricular enlargement), the last group had significantly higher ARs than the other two groups, showing that myocardiocyte apoptosis is increased in more unfavourable forms of cardiac remodelling. CONCLUSION: Patients with severely unfavourable cardiac remodelling, such as biventricular enlargement, have extremely high myocardiocyte apoptosis at necropsy, even late after LV myocardial infarction, supporting the role of myocardiocyte loss in determining post-infarction adverse remodelling.
Abstract: OBJECTIVES: The purpose of this study was to evaluate a potential correlation between apoptotic rate (AR), post-infarction left ventricular (LV) remodeling, and clinical characteristics in subjects who died late (>or=10 days) after an acute myocardial infarction (AMI) with evidence of persistent occlusion of the infarct-related artery at autopsy. BACKGROUND: Apoptosis contributes to myocardiocyte loss in cardiac disease and may have a pathophysiologic role in post-infarction LV remodeling. METHODS: The AR was calculated at the site of infarction and in remote unaffected LV regions, using co-localization of in situ end labeling for deoxyribonucleic acid fragmentation and immunohistochemistry for caspase-3, in 14 subjects who died within two months after AMI. Correlation between AR and clinical characteristics such as age, site of AMI, transmural extension, multivessel coronary disease, and signs and/or symptoms of heart failure (HF), at the time of initial hospitalization for AMI or subsequently before death, was assessed using non-parametric statistical tests. Parameters of LV remodeling including diameters, free wall thickness, diameter-to-wall-thickness ratio, and mass were measured at gross examination at autopsy. Values are expressed as median (interquartile range). RESULTS: Among clinical variables, early symptomatic post-infarction HF (9 cases, 64%) was associated with nearly fourfold increased AR at the site of infarction (26.2% [24.5% to 28.8%] vs. 6.4% [1.9% to 13.3%], p = 0.001). Moreover, AR both at the site of infarction and in unaffected regions was significantly correlated with parameters of progressive LV remodeling (p < 0.05). CONCLUSIONS: Our data show that in patients dying >or=10 days after AMI, myocardial apoptosis is strongly associated with and may be a major determinant of unfavorable LV remodeling and early symptomatic post-infarction HF.
Abstract: BACKGROUND: Coronary angioplasty and coronary artery bypass grafting (CABG) are both major techniques for the management of coronary artery disease, but CABG is associated with a lower incidence of repeat revascularization. Recent studies comparing angioplasty with stenting vs CABG have yielded conflicting results, with some suggesting improved survival with stenting, and others the opposite. We thus undertook a systematic overview of the randomized trials comparing stenting vs CABG in coronary artery disease. METHODS: MEDLINE (January 1986-February 2003), ISI Current Contents, the Cochrane Controlled Trial Register, LILACS and the American Heart Association, American College of Cardiology, European Society of Cardiology, and Transcatheter Cardiovascular Therapeutics conference proceedings were among the databases we searched. Abstraction was performed in a non-blinded manner on pre-specified forms. The random-effect odds ratios for death, myocardial infarction, stroke, repeat revascularization, and symptomatic angina were computed for the longest available follow-up. RESULTS: Nine randomized trials (3283 patients, representing only 6% of all screened subjects) with an average follow-up of 28 months were included in the analysis, while four studies were excluded because they were still unpublished, ongoing, or with non-systematic stenting. No study used drug-eluting stents. The odds ratios for stenting vs CABG were 0.82 (95% confidence interval-CI 0.57-1.18, p = 0.3) for the occurrence of death, non-fatal myocardial infarction or stroke, 4.6 (95% CI 3.5-5.9, p < 0.00001) for repeat revascularization, and 2.3 (95% CI 1.8-2.8, p < 0.00001) for symptomatic angina. Heterogeneity tests were not statistically significant. The results of sensitivity analysis were similar even after stratification for single vessel, off-pump, single center or high-quality studies. CONCLUSIONS: Overall and event-free survival after conventional stenting for coronary artery disease are similar to those after CABG, but surgery is still associated with a significantly lower incidence of repeat revascularization and symptoms. The role of next-generation drug-eluting stents in widening the indications for stenting and overcoming restenosis will need to be assessed in future observational and randomized studies comparing stenting vs CABG.
Abstract: BACKGROUND: Mediastinitis is a very serious complication after cardiac surgery. To date, the optimal treatment of mediastinitis is still controversial: the "closed wound" procedures and the "open wound" treatments are the two conventional modalities reported in the literature. METHODS: Between January 1995 and December 2000, 20 patients, who had previously been submitted to cardiac surgery, were treated by a modification of the "open wound" treatment strategy for postoperative mediastinitis. All patients were scheduled for 2, 6, and 12-month clinical follow-up. The procedure performed consisted of three major steps: 1) early sternum reopening, followed by phase 2) including irrigation of the wound 3 times daily, and the final step 3) of delayed reconstructive surgery using the pectoralis major myocutaneous advancement flap closure technique. We prospectively analyzed the short- and long-term results of these procedures. RESULTS: The overall duration of hospitalization was 25 +/- 10 days; no patient required intensive care unit permanency. Clinical success was achieved in all 20 cases (100%). No recurrences of local (such as fistulas or abscesses) or systemic infections were noted, and no patient required sternal reopening during follow-up. An optimal cosmetic result was obtained in all patients and only 2 cases had persistent sternal pain regressing at the 6-month follow-up control. CONCLUSIONS: Our data suggest that for patients with severe mediastinitis, this treatment strategy is safe. The clinical and esthetic success rates are high, the recovery time rapid, and the rates of short- and long-term complications very low.
Abstract: Diabetes represents a major cause of cardiovascular morbidity and mortality in developed countries, and atherothrombosis accounts for most deaths among diabetics. Recent evidence has reliably shown the relevant etiopathogenetic role of inflammation in atherothrombotic disease. This review summarizes and discusses the possible synergistic effects of diabetes and inflammation in promoting atherothrombosis and its complications, as well as potential avenues for diagnostic, preventive, and therapeutic benefits in the modulation of inflammatory mechanisms in diabetic atherothrombotic disease.
Abstract: BACKGROUND: Infarct-related artery (IRA) patency after acute myocardial infarction (AMI) is associated with a more favourable clinical course, in particular in patients with high-risk features. As it has been recently reported that IRA patency is associated with a reduced postinfarction apoptotic rate (AR), the aim of our study was to assess whether IRA status late after AMI had a different impact on AR in high- vs. low-risk patients. METHODS AND RESULTS: Co-localization of TUNEL and caspase-3 was used to calculate the AR at the site of infarction at the time of death in 30 subjects. The Norris coronary prognostic index (NI) was calculated (computing age, presence of pulmonary congestion, heart size and history of previous additional AMI) in order to define the patients' individual risk at the time of hospitalization. According to the NI (< or =7 vs. >7), subjects were divided into low and high risk, as NI >7 carries an approximate threefold higher risk of death. The NI was significantly correlated with the AR at the time of death both in infarct and remote areas. Twenty subjects had IRA occlusion at the time of death, and in these patients AR was significantly higher both in infarct and remote areas (P<0.001 and P=0.009 vs. the others, respectively). However the impact of IRA occlusion on AR was significantly different comparing high- vs. low-risk subjects. In particular, AR at the infarct site was 10-fold higher in the high-risk subjects with IRA occlusion (26.1%[20.4-28.7%]) vs. those with open IRA (2.3%[0.6-3.5%]; P=0.002) and was nonsignificantly different in the low-risk subjects vs. those without IRA occlusion (8.2%[2.5-17.5%] vs. 5.4%[1.5-7.9%]; P=0.48). Similarly, in the high-risk subjects, AR in remote areas was significantly greater in cases with occluded vs. open IRA (0.7%[0.4-0.9%] vs. 0.3%[0.3-0.32%]; P=0.009). CONCLUSION: A significantly higher AR is associated with IRA occlusion late post AMI in subjects with high-risk clinical features, and not in low-risk patients. The diverse impact of IRA occlusion on AR in subjects with different risk profiles may explain the greater benefit associated with coronary reperfusion in high-risk subjects. The overall lower AR in low-risk subjects, independently from the IRA status, may be correlated with the better long-term prognosis after AMI in this case.
Abstract: Despite diagnostic and therapeutic advances, the rate of event recurrence is still relatively high and short- and long-term prediction of risk is necessary although extremely challenging to provide optimal treatment to patients with acute coronary syndromes. Available data recommend the use of C-reactive protein (CRP) as a prognostic marker in patients with acute coronary syndromes in addition to other prognostic factors including troponin levels. Evaluation of CRP levels at time of admission should be included in the evaluation of the patient's risk profile, including clinical data, associated diseases, markers of myocardial necrosis (especially troponin levels), left ventricle performance, and age. A cutoff level of 10 mg/L for CRP may be used as a marker of higher risk for death and possibly myocardial infarction in acute coronary syndromes, and a cutoff of 3 mg/L identifies a group of patients with intermediate risk and a high rate of recurrent events.
Abstract: The open-artery hypothesis states that myocardial reperfusion, even if late for myocardial salvage, provides benefits and prevents adverse cardiac remodeling. While observational data in humans regarding the deleterious impact of a permanent infarct-related artery occlusion and the benefits of spontaneous reperfusion are quite consistent, the reports regarding late revascularization are inconclusive in order to prove such a hypothesis. The observational studies tend to have selection biases, while randomized trials to date are too small to be conclusive. Moreover, the pathophysiological mechanisms underlying presumed benefits of reperfusion are still unclear. However, although the open-artery hypothesis remains unproven, the current evidence suggesting benefits calls for additional studies. Limitations of ischemic left ventricular dilatation and myopathy could markedly reduce cardiovascular morbidity and mortality after acute myocardial infarction.
Abstract: Vasopressin is currently recommended in the management of patients with cardiac arrest, but its efficacy is still incompletely established. We systematically reviewed randomized trials comparing vasopressin to control treatment in the management of cardiac arrest in humans and animals. Two human and 33 animal studies were retrieved. At pooled analysis vasopressin appeared equivalent to adrenaline (epinephrine) in the management of human cardiac arrest (N=240), with, respectively 63 (78/124) vs 59% (68/116) ROSC (P=0.43), and 16 (20/124) vs 14% (16/116) survival to hospital discharge (P=0.52). In animal trials (N=669) vasopressin appeared instead significantly superior to both placebo (ROSC, respectively 93 [98/105] vs 19% [14/72], P<0.001) or adrenaline (ROSC, respectively 84 [225/268] vs 52% [117/224], P<0.001). In conclusion, vasopressin is superior to both placebo or adrenaline in animal models of cardiopulmonary resuscitation. Evidence in humans is still limited and confidence intervals estimates too wide to reliably confirm or disprove results obtained in experimental animal settings.
Abstract: BACKGROUND: Myocardial apoptosis persists beyond the acute phases of acute myocardial infarction (AMI) and is associated with left ventricular (LV) remodeling. Infarct-related artery (IRA) patency is considered a favorable prognostic factor after AMI and may be associated with more favorable LV remodeling because of reduced apoptosis at the site of AMI. The aim of this study was to assess the influence of IRA status on apoptotic rate (AR) in the hearts of subjects dying late after AMI. METHODS AND RESULTS: We used colocalization for in situ end-labeling of DNA fragmentation and immunohistochemistry for caspase-3 to calculate the AR at time of death (12 to 62 days after AMI) in 16 hearts with persistently occluded IRAs and in 8 hearts with patent IRAs. No significant differences were found when comparing the clinical characteristics of the 2 groups. Occluded IRA was associated with significantly higher AR at site of infarction (25.8% [interquartile range 20.9% to 28.5%] versus 2.3% [interquartile range 0.6% to 5.0%], P<0.001). This strong correlation between IRA occlusion and AR remained statistically significant even after correction for clinical characteristics such as sex, age, history of previous additional AMI or heart failure, transmural AMI, anterior AMI, fibrinolytic treatment, time from AMI to death, trauma as cause of death, and multivessel coronary disease (P=0.003). CONCLUSIONS: A significantly higher AR was associated with persistent IRA occlusion late post-AMI. These data may suggest that the post-AMI benefits observed with a patent IRA (the "open-artery hypothesis") may in part be due to reduced myocardial apoptosis.
Abstract: Apoptosis may represent an important pathophysiological mechanism causing progressive myocardiocyte loss and left ventricular dilation, even late after acute myocardial infarction (AMI). This review discusses the role of myocardial apoptosis on the basis of findings from experimental studies in animals and from observational studies in humans with the purpose of assessing the clinical relevance, determinants and mechanisms of myocardial apoptosis and the potential therapeutic implications. A more profound understanding of the impact of myocardiocyte loss on prognosis and of the mechanisms involved may lead to an improved understanding of cardiac remodeling and possibly to an improved patient care. In fact, among the potential modulators of myocardial apoptosis, angiotensin-converting enzyme inhibitors and beta-adrenergic receptor blockers have already been shown to improve the prognosis and symptoms in patients with post-infarction heart failure, and a reduction in myocardial apoptosis could partly contribute to such a beneficial effect. Several other putative factors could also modulate myocardial apoptosis after AMI, and many are currently under intense investigation. In particular, the infarct-related artery patency late after AMI may be a major clinical determinant of myocardial apoptosis and clinical benefits deriving from an open artery (the "open-artery hypothesis"), such as a slowing down of the remodeling process and a reduced arrhythmic risk, could be due, at least in part, to a reduced apoptotic myocardiocyte loss.
Abstract: Left ventricular (LV) remodeling and heart failure (HF) complicate acute myocardial infarction (AMI) even weeks to months after the initial insult. Apoptosis may represent an important pathophysiologic mechanism causing progressive myocardiocyte loss and LV dilatation even late after AMI. This review will discuss the role of apoptosis according to findings in animal experimental data and observational studies in humans in order to assess clinical relevance, determinants, and mechanisms of myocardial apoptosis and potential therapeutic implications. More complete definition of the impact of myocardiocyte loss on prognosis and of the mechanisms involved may lead to improved understanding of cardiac remodeling and possibly improved patients' care. Mitochondrial damage and bcl-2 to bax balance play a central role in ischemia-dependent apoptosis while angiotensin II and beta(1)-adrenergic-stimulation may be major causes of receptor-mediated apoptosis. Benefits due to treatment with ACE-inhibitors and beta-blockers appear to be in part due to reduced myocardial apoptosis. Moreover, infarct-related artery patency late after AMI may be a major determinant of myocardial apoptosis and clinical benefits deriving from an open artery late post AMI (the "open artery hypothesis") may be, at least in part, due to reduced myocardiocyte loss.
Abstract: In the last years new computer-based imaging techniques, like color Doppler sonography, Computed Tomography, and Magnetic Resonance, have allowed a non-invasive approach to vascular diseases, partially replacing angiography, and increasing the role of radiology in the diagnosis and management of many chronic diseases, such as Takayasu's arteritis. Simultaneous evaluation of luminal and vascular wall changes may now allow a simpler diagnosis of this condition also in its early phase and the effective therapy monitoring. Application of new procedures of interventional radiolgy provides a safer and more conservative correction of late steno-occlusive complications. Familiarity with the different imaging features of Takayasu arteritis will permit a more accurate clinical diagnosis and management of this insidious disorder.
