Luigi La Vecchia

Cardiac troponin I as diagnostic and prognostic marker in severe heart failure.

BACKGROUND Cardiac cell death has been shown to occur in heart failure and has been implicated as one of the mechanisms responsible for progression of the disease. Cardiac Troponin I (cTnI) represents a highly sensitive marker for myocardial cell death. Based on previous studies reporting that cTnI may be detected in patients with heart failure, we evaluated the clinical correlates and prognostic implications of detectable cTnI in a consecutive series of patients with severe heart failure. METHODS Thirty-four patients were examined. Upon admission, we measured serum levels of cTnI by conventional immunoenzymatic assay (Stratus Dade II). According to the results of this assay, patients were divided into 2 groups, based on the presence (cTnI+) or absence (cTnI-) of detectable cTnI. These 2 groups were compared by non-parametric analysis for their clinical characteristics, instrumental findings, and short-term outcome. RESULTS The cTnI+ group included 10 patients (29%) with a mean serum cTnI of 0.7 +/- 0.3 ng/ml. Compared with the cTnI- group, these patients had significantly lower left ventricular ejection fractions (20% +/- 5% vs 26% +/- 7%, p = 0.023) and a trend for higher systolic pulmonary artery pressure (59 +/- 17 mm Hg vs 49 +/- 13 mm Hg, p = 0.08). In cTnI+ patients, the correlation between cTnI levels upon admission and ejection fraction was r = -0.530 (p = 0.11). We found ischemic etiology was equally present in the 2 groups, whereas we never found histologic signs of acute myocarditis. Other clinical characteristics (functional class, daily diuretic dose, need for intravenous inotropes) were not statistically different in the 2 groups. In cTnI+ patients who improved after admission, cTnI became undetectable after a few days; in patients with refractory heart failure who were hospitalized until death, cTnI persisted in detectable levels throughout the observation period. Using the Cox proportional hazard model, a positive cTnI was the most powerful predictor of mortality at 3 months (p = 0.013; hazard ratio 6.86; 95% confidence interval 1.32 to 35.4). CONCLUSIONS These observations suggest that cTnI is detected in the blood of 25% to 33% of patients with severe heart failure; its presence may help to identify a high-risk sub-group who faces very poor short-term prognosis.

Detectable serum troponin I in patients with heart failure of nonmyocardial ischemic origin

Cardiac troponin I, a specific and sensitive marker of myocardial damage, was detected in the blood of 6 of 26 patients studied in our Heart Failure Clinic. In these patients functional class, ventricular function, and prognosis were significantly worse than in those without detectable troponin I. This study suggests that troponin I may represent the biochemical marker of myocardial damage occurring in severe heart failure.

Efficacy and safety of catheter ablation versus antiarrhythmic drugs for atrial fibrillation: a meta-analysis of randomized trials

Background Atrial fibrillation is the most common arrhythmia in clinical practice. Its treatment is still widely debated due to the large variety of therapeutic options. Radiofrequency catheter ablation (RFCA) around pulmonary vein ostia and in the left atrium has been proposed as a technique to cure atrial fibrillation and is now performed with increasing success worldwide. However, few randomized controlled trials (RCTs) are available. Some of these have been published recently and are not yet included in meta-analyses. Objectives We conducted a meta-analysis to summarize the current evidence base for the efficacy and safety of RFCA in patients with atrial fibrillation. Methods We searched electronic databases for relevant RCTs comparing RFCA with antiarrhythmic drugs for the management of atrial fibrillation. Recurrence of any atrial tachyarrhythmia (including atrial fibrillation, atrial flutter and atrial tachycardia) and rate of complications and adverse events were the end-points of the analysis. The results are reported as relative risk and 95% confidence interval, calculated using RevMan 5. Results A total of eight RCTs were identified including 844 patients. Overall, 98 (23.2%) of 421 patients in the treatment group and 324 (76.6%) of 423 patients in the control group had atrial tachyarrhythmia recurrence. RFCA decreased atrial tachyarrhythmia recurrence by 71% (relative risk 0.29, 95% confidence interval 0.20–0.41, P < 0.00001, with random effects model). Fewer complications and adverse events were reported in the ablation group compared with the control group (relative risk 0.72, 95% confidence interval 0.40–1.30, P = 0.28, with random effects model). Conclusion In selected patients with atrial fibrillation, RFCA is a relatively effective and well-tolerated procedure to cure atrial fibrillation. Even though the results of our systematic review favour ablation therapy, large, well-designed RCTs are needed to confirm the efficacy and safety of RFCA for the management of atrial fibrillation.

Troponin T, troponin I and creatine kinase-MB mass after elective coronary stenting.

Objective To assess whether and to what extent elective coronary stenting is associated with biochemical evidence of minor myocardial damage (MMD), as defined by the detection of abnormal post-procedural serum levels of one or more among the following markers of ischaemic injury: creatine kinase (CK)-MB mass, troponin T (Tn-T) and troponin I (Tn-I).Methods Nineteen elective procedures of coronary stenting were compared with a matched group of 25 conventional percutaneous transluminal coronary angioplasty (PTCA) procedures performed in our laboratory from March to June 1995. Cases with evolving or recent (< 2 weeks) myocardial infarction, chronic total occlusions and dilatation of saphenous vein grafts were excluded. By definition, all of the patients had undergone uneventful deployment of a single Palmaz-Schatz stent, with no chest pain and no persistent ECG changes after the procedure. Serum levels of CK-MB mass, Tn-T and Tn-I were determined at baseline and 6, 12 and 24 h after the procedure. The frequency of abnormal results was determined for each marker. Baseline and peak post-procedural levels in the two groups were compared and related to procedural variables.Results Baseline values were normal in all cases. The quantitative analysis showed that post-procedural levels of each marker (including total CK) were significantly higher with respect to baseline in both groups. In the stent group, two patients had positive CK-MB mass, four positive Tn-T and seven positive Tn-I. Absolute changes in Tn-T and Tn-I were closely related to changes in CK-MB mass (r = 0.76, P < 0.0001; r = 0.90, P < 0.0001, respectively). Three of these patients developed clinically silent side-branch occlusion. All of them were positive for troponins and two were positive for CK-MB. No correlation was found between procedural variables and the results of biochemical assays. In the PTCA group, three patients were positive for Tn-I, whereas the CK-MB mass and Tn-T remained constantly normal. No side-branch occlusion was observed. The peak CK-MB mass and Tn-I were significantly higher in the stent group than they were in the PTCA group (3.04 ± 4.1 versus 1.27 ± 1.3 ng/ml, P = 0.046; 0.78 ± 1.17 versus 0.28 ± 0.3 ng/ml, P = 0.046, respectively). This difference was no longer apparent when patients with side-branch occlusion were excluded.Conclusions In our series, Tn-I measurement shows the highest ability to detect MMD, being positive in 37% of stent and 14% of PTCA cases. Elective coronary stenting is associated with greater release of CK-MB mass and Tn-I than is conventional PTCA. This finding is mainly determined by cases of side branch occlusion, which account for most, but not all, periprocedural MMD in the stent group.

Periprocedural management and in-hospital outcome of patients with indication for oral anticoagulation undergoing coronary artery stenting.

PURPOSE In patients on oral anticoagulation (OAC) undergoing coronary stenting (PCI-S), procedural management and in-hospital outcome have never been specifically and prospectively investigated. Also, the contribution of early bleeding to the relevant hemorrhagic rate reported at follow-up with triple therapy of OAC, aspirin, and clopidogrel is largely unknown. METHODS Consecutive patients with indication for OAC undergoing PCI-S at 5 centers were enrolled and prospectively evaluated. RESULTS Out of 3410 patients undergoing PCI-S in the study period, indication for OAC was present in 4.8%. Femoral approach and bare metal stents were the most frequently used. During PCI-S, OAC was continued in about 30% of patients, whereas in about 20% heparin bridging was carried out. Glycoprotein IIb/IIIa inhibitors were rarely used (11%), whereas a standard bolus of unfractionated heparin was given in 93% of cases. Major adverse cardiovascular events (MACE) occurred in 4.8% of patients and major bleeding in 4.3%. No predictors of MACE or bleeding were identified, although the femoral approach was of borderline significance for major bleeding (OR 4.6, 95% CI 1.0-20.8; P = 0.05). A history of previous hemorrhage (OR 5.3, 95% CI 1.6-18.1; P = 0.007) predicted Carbofilm-coated stent implantation. CONCLUSIONS A limited, albeit clinically relevant, proportion of patients undergoing PCI-S has indication for OAC. Procedural management appears not substantially different from that of common patients. In-hospital major bleeding is relevant and should be taken into account when evaluating the overall hemorrhagic rate at a medium- to long-term follow-up.

Left ventricular versus biventricular dysfunction in idiopathic dilated cardiomyopathy

Eighty-five consecutive patients with idiopathic dilated cardiomyopathy were categorized according to the presence (biventricular dysfunction) or absence (left ventricular [LV] dysfunction) of reduced right ventricular ejection fraction (<35%) along with reduced LV ejection fraction (<50%). Compared with the 36 patients with LV dysfunction, the 49 patients with biventricular dysfunction had significantly worse New York Heart Association functional class (2.7+/-0.6 vs 1.9+/-0.5; p <0.001), LV ejection fraction (26+/-10% vs 34+/-8%; p <0.0001), and outcome (transplant-free survival, 55% vs 89%; p <0.001). Thus, dilated cardiomyopathy is frequently characterized by biventricular involvement, which identifies a more severe disease and a worse long-term prognosis.

Ventricular late potentials, interstitial fibrosis, and right ventricular function in patients with ventricular tachycardia and normal left ventricular function

We examined 40 patients with ventricular tachycardia (VT) and no evidence of heart disease, and found a 50% prevalence of ventricular late potentials (VLPs) on the signal-averaged electrocardiogram. This finding was associated with a significantly higher content of fibrous tissue on endomyocardial biopsy and a lower right ventricular ejection fraction. Thus, VLPs are frequently found in idiopathic VT, are a marker for subclinical anatomic and functional abnormalities of the right ventricle, and may be associated with a worse outcome.

A Clinical and Angiographic Study of the XIENCE V Everolimus-Eluting Coronary Stent System in the Treatment of Patients With Multivessel Coronary Artery Disease: The EXECUTIVE Trial (EXecutive RCT: Evaluating XIENCE V in a Multi Vessel Disease)

OBJECTIVES This study sought to investigate the efficacy and performance of the XIENCE V everolimus-eluting stent (EES) (Abbott Vascular, Santa Clara, California) in the treatment of de novo coronary lesions in patients with 2- to 3-vessel multivessel coronary artery disease (MV-CAD). BACKGROUND Drug-eluting stents (DES) have emerged as an alternative to conventional coronary artery bypass surgery in patients with MV-CAD although first-generation DES yielded inferior efficacy and safety compared with surgery. METHODS Prospective, randomized (1:1), multicenter feasibility trial was designed to assess angiographic efficacy of EES compared with the TAXUS paclitaxel-eluting stent (PES) in 200 patients, and a prospective, open-label, single-arm, controlled registry was designed to analyze the clinical outcome of EES at 1-year follow-up in 400 MV-CAD patients. For the randomized trial, the primary endpoint was in-stent late loss at 9 months. For the registry, the primary endpoint was a composite of all-cause death, myocardial infarction, and ischemia-driven target vessel revascularization at 12 months. RESULTS The primary endpoint per single lesion was significantly lower in the EES group compared with the PES group (-0.03 ± 0.49 mm vs. 0.23 ± 0.51 mm, p = 0.001). Similar results were observed when analyzing all lesions (0.05 ± 0.51 mm vs. 0.24 ± 0.50 mm, p < 0.001). Clinical outcome at 1 year yielded a composite of major adverse cardiac events of 9.2% in the single-arm registry, and 11.1% and 16.5% in the EES and PES randomized groups, respectively (p = 0.30). CONCLUSIONS The EXECUTIVE trial was a randomized pilot trial dedicated to the comparison of the efficacy of 2 different DES among patients with 2- to 3-vessel MV-CAD. The study shows lower in-stent late loss at 9 months with the EES XIENCE V compared with the PES TAXUS Libertè, and a low major adverse cardiac event rate at 1 year in patients with 2-to 3-vessel MV-CAD. (EXECUTIVE [EXecutive RCT: Evaluating XIENCE V in a Multi Vessel Disease]; NCT00531011).

Right ventricular function predicts transplant-free survival in idiopathic dilated cardiomyopathy.

Background Right ventricular function may be reduced in patients with idiopathic dilated cardiomyopathy (IDC). The prognostic implications of right ventricular dysfunction have not been investigated in this group of patients. Methods In a series of 120 consecutive patients with IDC [defined as a left ventricular ejection fraction (LVEF) < 55%, normal coronary arteries and no other causes for left ventricular dysfunction], right ventricular function was prospectively evaluated by means of angiocardiography at the time of catheterization. A head-to-head comparison of ventricular volumes, ejection fraction, end-diastolic pressure, stroke work index and end-systolic pressure/volume ratio of the left and right ventricle was performed according to the Coxs proportional hazard method for the pre-defined end-point of transplant-free survival. Results In the study population, LVEF was 31 ± 11% and right ventricular ejection fraction (RVEF) was 34 ± 10%. After a mean follow-up of 30 months (range 12–120 months), 26 patients died (22%) and 14 (12%) underwent heart transplantation. At univariate analysis, all the above mentioned parameters were significantly (P < 0.0001) associated with outcome except left and right ventricular end-systolic pressure/volume ratio. At multivariate analysis, independent predictors of transplant-free survival were RVEF (P = 0.001), right ventricular stroke work index (P = 0.015), right ventricular end-diastolic volume (P = 0.034) and left ventricular end-diastolic volume (P = 0.048), but not LVEF. The same relation holds true considering the end point of total mortality. Conclusions Parameters of right ventricular function are strong predictors of survival in IDC, even in patients enrolled over a wide range of LVEFs. The present study suggests that right ventricular function should be evaluated in patients with IDC. A large non-invasive based study on right ventricular function in IDC appears to be warranted.

Systematic coronary stenting after failed thrombolysis in high-risk patients with acute myocardial infarction: procedural results and long-term follow-up.

Background Stenting in acute myocardial infarction (AMI) represents a feasible and effective revascularization strategy. However, very little information is available for patients who receive a stent after failed thrombolysis (socalled ‘rescue’ stenting). Methods We analysed the procedural results and the 2‐year follow‐up of all consecutive patients with moderateto‐large AMI treated with rescue stenting in the period 1996‐2001. Results The study cohort includes 123 patients (mean age 60 ±12 years, 78% men). Coronary angiography showed multivessel disease in 47% of patients; the infarct‐related vessel was the left anterior descending coronary artery in 47%, the right coronary artery in 41%, the left circumflex coronary artery in 9.5% and a saphenous vein graft in 2.5%. Baseline Thrombolysis in Myocardial Infarction (TIMI) flow was grade 0‐1 in 65% and grade 2 in 25%. Coronary stenting was attempted in all 123 patients and was successful in 119 out of 123 (96.7%); abciximab was used in 57 out of 123 (46%) and intra‐aortic balloon pumping in 35 out of 123 (28%). At the end of the procedure, TIMI 3 flow was obtained in 104 out of 123 (85%) and TIMI 2 flow in 14 out of 123 (11%). There were 10 in‐hospital deaths and four late deaths, with a long‐term survival of 88.6%. This figure increases to 95.2% if patients presenting with cardiogenic shock are excluded. A new revascularization procedure was performed in 21% of discharged patients (in the target vessel for 12% and in non‐target vessels for 9%). Overall, event‐free survival at 2 years was 69%. At multivariate analysis, independent predictors of survival were age (P = 0.014) and ejection fraction (P = 0.006). Conclusions This report represents one of the first series concerning long‐term follow‐up after rescue stenting. The main results include a high procedural feasibility, a low late mortality and a target vessel revascularization rate in the range expected with stenting. These data must be viewed as part of the constant effort to optimize revascularization strategies in AMI. Coron Artery Dis 14:395‐400