Luigi Ferrara

Carvedilol increases two-year survivalin dialysis patients with dilated cardiomyopathy: a prospective, placebo-controlled trial.

OBJECTIVES We sought to evaluate the effects of carvedilol on mortality and morbidity in dialysis patients with dilated cardiomyopathy. BACKGROUND Several lines of evidence support the concept that therapy with beta-blocking agents reduces morbidity and mortality in patients with congestive heart failure (HF), but the demonstration of such a survival benefit in dialysis patients with dilated cardiomyopathy is still lacking. METHODS A total of 114 dialysis patients with dilated cardiomyopathy were randomized to receive either carvedilol or placebo in addition to standard therapy. A first analysis was performed at one year and was followed by an additional follow-up period of 12 months. RESULTS Two-year echocardiographic data revealed a significant attenuation of pathologic remodeling, with smaller cavity diameters and higher ejection fractions in the active treatment group than in the placebo group. At two years, 51.7% of the patients died in the carvedilol group, compared with 73.2% in the placebo group (p < 0.01). Furthermore, there were significantly fewer cardiovascular deaths (29.3%) and hospital admissions (34.5%) among patients receiving carvedilol than among those receiving a placebo (67.9% and 58.9%, respectively; p < 0.00001). The exploratory analyses revealed that fatal myocardial infarctions, fatal strokes, and hospital admissions for worsening HF were lower in the carvedilol group than in the placebo group. A reduction in sudden deaths and pump-failure deaths was also observed, though it did not reach statistical significance. CONCLUSIONS Carvedilol reduced morbidity and mortality in dialysis patients with dilated cardiomyopathy. These data suggest the use of carvedilol in all dialysis patients with chronic HF.

Clinical researchCarvedilol increases two-year survivalin dialysis patients with dilated cardiomyopathy: A prospective, placebo-controlled trial

OBJECTIVES We sought to evaluate the effects of carvedilol on mortality and morbidity in dialysis patients with dilated cardiomyopathy. BACKGROUND Several lines of evidence support the concept that therapy with beta-blocking agents reduces morbidity and mortality in patients with congestive heart failure (HF), but the demonstration of such a survival benefit in dialysis patients with dilated cardiomyopathy is still lacking. METHODS A total of 114 dialysis patients with dilated cardiomyopathy were randomized to receive either carvedilol or placebo in addition to standard therapy. A first analysis was performed at one year and was followed by an additional follow-up period of 12 months. RESULTS Two-year echocardiographic data revealed a significant attenuation of pathologic remodeling, with smaller cavity diameters and higher ejection fractions in the active treatment group than in the placebo group. At two years, 51.7% of the patients died in the carvedilol group, compared with 73.2% in the placebo group (p < 0.01). Furthermore, there were significantly fewer cardiovascular deaths (29.3%) and hospital admissions (34.5%) among patients receiving carvedilol than among those receiving a placebo (67.9% and 58.9%, respectively; p < 0.00001). The exploratory analyses revealed that fatal myocardial infarctions, fatal strokes, and hospital admissions for worsening HF were lower in the carvedilol group than in the placebo group. A reduction in sudden deaths and pump-failure deaths was also observed, though it did not reach statistical significance. CONCLUSIONS Carvedilol reduced morbidity and mortality in dialysis patients with dilated cardiomyopathy. These data suggest the use of carvedilol in all dialysis patients with chronic HF.

Dilated Cardiomyopathy in Dialysis Patients— Beneficial Effects of Carvedilol: A Double-Blind, Placebo-Controlled Trial

OBJECTIVES The aim of this study was to investigate in dialysis patients with symptomatic heart failure New York Heart Association (NYHA) functional class II or III whether the addition of carvedilol to conventional therapy is associated with beneficial effects on cardiac architecture, function and clinical status. BACKGROUND Congestive heart failure (CHF) in chronic hemodialyzed patients, particularly when associated with dilated cardiomyopathy, represents an ominous complication and is an independent risk factor for cardiac mortality. METHODS We enrolled 114 dialysis patients with dilated cardiomyopathy. All patients were treated with carvedilol for 12 months in a double-blind, placebo-controlled, randomized trial. The patients underwent M-mode and two-dimensional echocardiography at baseline, 1, 6 and 12 months after the randomization. Each patients clinical status was assessed using an NYHA functional classification that was determined after 6 and 12 months of treatment. RESULTS Carvedilol treatment improved left ventricular (LV) function. In the active-treatment group, the increase in LV ejection fraction (from 26.3% to 34.8%, p < 0.05 vs. basal and placebo group) and the reduction of both LV end-diastolic volume (from 100 ml/m2 to 94 ml/m2, p < 0.05 vs. basal and placebo group) and end-systolic volume (from 74 ml/m2 to 62 ml/m2, p < 0.05 vs. basal and placebo group) reached statistical significance after six months of therapy, compared with baseline and corresponding placebo values, and they remained constant at one year of treatment (p < 0.05 vs. basal and placebo group). The clinical status of patients, assessed by NYHA functional classification, improved during the treatment period. Moreover, at the end of the trial, there were no patients in NYHA functional class IV in the carvedilol group, compared with 5.9% of the patients in the placebo arm. CONCLUSIONS One year of therapy with carvedilol in dialysis patients with CHF and dilated cardiomyopathy reduces LV volumes and improves LV function and clinical status.

Ventricular tachyarrhythmias following coronary surgery : predisposing factors

The perioperative factors potentially associated with post-coronary artery bypass grafting (CABG) ventricular tachyarrhythmias (VT) onset have not been deeply investigated. Monomorphic or polymorphic ventricular tachycardia and ventricular fibrillation represent the most dreadful arrhythmic events that can complicate the postoperative course of CABG. As a consequence, the aim of our paper was to identify which perioperative variables might predict post-CABG VT occurrence. One hundred and fifty-two consecutive patients who underwent CABG surgery at our Institution were included in the study. Post-CABG VT occurred in 13 out of 152 patients (8.5%, six cases of monomorphic ventricular tachycardia and seven cases of ventricular fibrillation). At univariate analysis, VT patients were significantly younger (54.8+/-6.6 vs. 60.1+/-8.8, P=0.038), exhibited a more severe coronary artery disease (CAD) (number of diseased vessels 2.92+/-0.3 vs. 2.45+/-0.7, P=0.023, and percentage of patients with three-vessel CAD 91.7% vs. 57.3%, P=0.043) and received a greater number of CABGs than those remaining in sinus rhythm (SR) (percentage of patients receiving three or more CABGs 76. 9% vs. 38.8%, P1000 76.9% vs. 38%, Pnormal range 72.7% vs. 30.7%, P=0.014), electrolyte derangement (84.6% vs. 45.6%, P=0.017) and a severe haemodynamic impairment (need for IABP 23% vs. 2.9%, P1000, postoperative electrolyte imbalance, the need for three or more CABGs and of IABP all were independent correlates for VT. In conclusion, post-CABG VT seem to be related to the preexistence of a severe underlying coronary artery disease along with perioperative triggering factors such as acute ischemia, electrolytic disorders and a sudden haemodynamic impairment.

Perioperative correlates of malignant ventricular tachyarrhythmias complicating coronary surgery.

SummarySustained ventricular tachyarrhythmias (VT), such as monomorphic or polymorphic ventricular tachycardia, and ventricular fibrillation, represent the most serious arrhythmic events that can complicate the postoperative course of coronary artery bypass grafting (CABG). The perioperative factors potentially associated with post-CABG sustained VT onset have not been thoroughly investigated. As a consequence, the aim of our study was to identify which perioperative variables might predict post-CABG VT occurrence.One hundred and fifty-two consecutive patients who underwent CABG surgery at our Institute were included in the study. Post-CABG VT occurred in 13 out of 152 patients (8.5%, six cases of monomorphic ventricular tachycardia and seven cases of ventricular fibrillation). Univariate analysis revealed that VT patients were significantly younger (54.8 ± 6.6 vs 60.1 ± 8.8,P = 0.038), exhibited more severe coronary artery disease (CAD) (no. of diseased vessels, 2.92 ± 0.3 vs 2.45 ± 0.7,P = 0.023; and percentage of patients with three-vessel CAD, 91.7 vs 57.3%,P = 0.043), and received a greater number of CABGs than those remaining in sinus rhythm (SR) (percentage of patients receiving three or more CABGs, 76.9 vs 38.8%,P = 0.018) Moreover, VT patients more frequently developed intra- or postoperative myocardial infarction (total CK > 1000, 76.9 vs 38%,P = 0.016; and MB-CK > normal range, 72.7 vs 30.7%,P = 0.014), electrolyte derangement (84.6 vs 45.6%,P = 0.017), and a severe hemodynamic impairment (need for intra-aortic balloon pump (IABP), 23 vs 2.9%,P = 0.009). On multivariate analysis, total CK > 1000, postoperative electrolyte imbalance, the need for three or more CABGs, and for IABP all were independent correlates for VT.In conclusion, post-CABG VT seem to be related to the preexistence of a severe underlying coronary artery disease along with perioperative triggering factors, such as acute ischemia, electrolytic disorders, and sudden hemodynamic impairment.

Sustained-Release Diltiazem Reduces Myocardial Ischemic Episodes in End-Stage Renal Disease: A Double-Blind, Randomized, Crossover, Placebo-Controlled Trial

End-stage renal disease (ESRD) patients receiving maintenance hemodialysis and suffering from coronary artery disease (CAD) often receive doses of calcium channel antagonists that are too low. This may be the result of physicians desire to avoid adverse side effects during hemodialysis. The aim of this study was the assessment of the safety and efficacy of incremental doses of diltiazem for the treatment of myocardial ischemia in ERSD patients with CAD to identify the optimal dose of the drug. A total of 196 chronic hemodialysis patients were enrolled with CAD showing more than 5 min of transient myocardial ischemia during a 48-h Holter ECG monitoring. A double-blind, randomized, crossover, placebo-controlled trial design was used. Incremental doses of diltiazem (120 to 240 mg/d) were administered in 4 mo. With a dose of 120 and 180 mg/d, a significant reduction in the number and duration of total and symptomatic ischemic episodes was observed (P < 0.001), but the number and the duration of silent ischemic episodes were not reduced. Conversely, the efficacy on silent myocardial ischemia was obtained with a dosage of diltiazem of 240 mg/d (P < 0.001). In addition, with a sustained-release formulation (120 mg twice daily), the efficacy was similar to that obtained with four 60-mg tablets, but the safety was improved, especially during hemodialytic session. The circadian variations analysis of transient ischemic episodes showed a significant reduction in both ischemic peaks observed at baseline only with 240 mg/d of diltiazem. The findings emphasize that sustained-release diltiazem (120 mg twice daily) can be largely useful in uremic patients with CAD on maintenance dialysis. Diltiazem reduces the number and the duration of silent ischemic episodes, has a good tolerability, and positively modifies the circadian pattern of ischemic episodes.