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Introduction: The relative effectiveness of the implantable cardioverter defibrillator (ICD) and antiarrhythmic drugs (AADs) varies with left ventricular ejection fraction (LVEF). However, once an ICD or AAD treatment strategy is chosen, the degree to which the LVEF influences survival is unknown. This article addresses that question., Methods and Results: Using patient data from the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial, the impact of LVEF on prognosis of patients who were treated with either an ICD or AAD was assessed. Survival within each quintile of LVEF was estimated by the method of Kaplan-Meier for patients treated with either the ICD or AADs. The Cox proportional hazards model was used to investigate the prognostic value of LVEF for estimating survival after adjustment for other baseline covariates among all patients in the subgroups treated by ICD or AAD. In the highest two quintiles of LVEF, survival was comparable in AAD-treated and ICD-treated patients. In the AAD-treated patients, higher LVEF was significantly and independently associated with survival free of all-cause mortality and arrhythmic death. In the ICD-treated patients, however, the statistical significance of the association was lost and only a trend toward greater survival was present. Death due to congestive heart failure remained independently and significantly associated with survival in both AAD-treated and ICD-treated patients., Conclusion: In patients treated with AADs but not patients treated with ICDs, survival is strongly associated with LVEF. The absence of a statistically significant association in the ICD patients is likely related to the effectiveness of the ICD in treating malignant ventricular arrhythmias, but a chance lack of association cannot be excluded.

Background: Although beta-adrenergic-receptor antagonists reduce morbidity and mortality in patients with mild-to-moderate chronic heart failure, their effect on survival in patients with more advanced heart failure is unknown., Methods: A total of 2708 patients with heart failure designated as New York Heart Association (NYHA) functional class III (in 92 percent of the patients) or IV (in 8 percent) and a left ventricular ejection fraction of 35 percent or lower were randomly assigned to double-blind treatment with either bucindolol (1354 patients) or placebo (1354 patients) and followed for the primary end point of death from any cause., Results: The data and safety monitoring board recommended stopping the trial after the seventh interim analysis. At that time, there was no significant difference in mortality between the two groups (unadjusted P=0.16). The results presented here are based on complete follow-up at the time of study termination (average, 2.0 years). There were a total of 449 deaths in the placebo group (33 percent) and 411 deaths in the bucindolol group (30 percent; adjusted P=0.13). The risk of the secondary end point of death from cardiovascular causes was lower in the bucindolol group (hazard ratio, 0.86; 95 percent confidence interval, 0.74 to 0.99), as was the risk of heart transplantation or death (hazard ratio, 0.87; 95 percent confidence interval, 0.77 to 0.99)., Conclusions: In a demographically diverse group of patients with NYHA class III and IV heart failure, bucindolol resulted in no significant overall survival benefit.

This article contains the results of an attempt by appointed members of the North American Society of Pacing and Electrophysiology to define the research frontier in electrophysiology and suggest areas of study as an aid in setting the research agenda.

Arterial stiffness, as evidenced by increased pulse pressure (PP), is associated with adverse cardiovascular events. However, the prognostic importance of PP in patients who have undergone revascularization is unknown. We examined the prognostic importance of PP and predictors of increased PP in patients entered into the Balloon Angioplasty Revascularization Investigation (BARI). Estimated correlation and standardized regression coefficients were reported, indicating the relative magnitude of independent effects of baseline characteristics on PP. The independent association of PP and outcome over 5 years was determined. Baseline characteristics independently associated with PP were higher mean arterial pressure, older age, female sex, noncoronary vascular disease, history of diabetes mellitus, and history of hypertension (p <0.001 for all). Cox regression covariates significantly associated with time to death were age, smoking, male gender, diabetes history, congestive heart failure, and baseline use of angiotensin-converting enzyme inhibitors, diuretic, or digitalis. When PP was added to the model, it was found to be an independent predictor of time to death (p = 0.008). When PP and mean arterial pressure were added to the model, PP remained significantly associated with time to death (p = 0.033). When renal disease and noncoronary vascular disease were added to the model, the relative risk declined from 1.07 to 1.04 and the association was no longer statistically significant. Thus, increased PP is directly and independently associated with mean arterial pressure, hypertension, age > or =65 years, diabetes mellitus, and the presence of noncoronary vascular disease, and inversely associated with a history of myocardial infarction. After coronary revascularization, PP, reflecting arterial stiffness, is independently associated with total mortality.

Objectives: The study was done to assess patients in the Post-Coronary Artery Bypass Graft (Post-CABG) trial to determine prognostic factors for atherosclerosis progression., Background: Saphenous vein grafts (SVGs) are effective in relieving angina and, in certain patient subsets, in prolonging life. However, the progression of atherosclerosis in many of these grafts limits their usefulness., Methods: The Post-CABG trial studied moderate versus aggressive lipid-lowering and low-dose warfarin versus placebo in patients with a history of coronary artery bypass surgery and found that more aggressive lipid lowering was effective in preventing progression of atherosclerosis in SVGs, but warfarin had no effect. Using variables measured at baseline, we sought the independent prognostic factors for atherosclerosis progression in SVGs, employing the statistical method of generalized estimating equations with a logit-link function., Results: Twelve independent prognostic factors for atherosclerosis progression were found. In the order of their importance they were: maximum stenosis of the graft at baseline angiography, years post-SVG placement; the moderate low-density lipoprotein-cholesterol (LDL-C) lowering strategy; prior myocardial infarction; high triglyceride level; small minimum graft diameter; low high-density lipoprotein-cholesterol (HDL-C); high LDL-C; high mean arterial pressure; low ejection fraction; male gender; and current smoking., Conclusions: This study identified Post-CABG patient and SVG characteristics associated with saphenous vein graft atherosclerosis progression. These data provide a basis for rational risk factor management to prevent progression of SVG atherosclerosis.

Data, largely from randomized, controlled trials, have clarified the role of the various treatment modalities in preventing sudden cardiac death. The therapeutic usefulness in sudden cardiac death prevention of antirarrhythmic and other drugs, and of the implantable cardioverter-defibrillator, is discussed. The relative effectiveness of the various modalities is also considered and conclusions about an appropriate treatment paradigm and future research directions are discussed.

Objectives: We sought to evaluate the safety and efficacy of carotid artery stenting (CAS) in high risk patients., Background: Carotid endarterectomy (CE) has been shown to be more effective than medical therapy, but it has limitations. Carotid artery stenting may be a reasonable alternative, particularly in high-risk patients., Methods: We prospectively evaluated the safety and efficacy of CAS in 170 consecutive patients who underwent the procedure in 192 carotid arteries. Of the patients enrolled, 129 (76%) would have been excluded from the major trials of CE and 54 (32%) were referred by vascular surgeons. This series represents a very high-risk group that included patients with unstable angina, previous ipsilateral CE, contralateral carotid artery occlusion and other severe comorbid illnesses. Only 25 (24%) of 104 symptomatic patients would have met the North American Symptomatic Carotid Endarterectomy Trial (NASCET) entry criteria. The patients' mean age was 73 +/- 8 years (95 confidence interval [CI] 57 to 89), and 42 patients (25%) were > or = 80 years old. Patients had an independent neurologic examination before and after the procedure., Results: The procedural success rate was 99%, including 73 patients who had a coronary intervention. Mean carotid artery stenosis was 78 +/- 10% before (95 CI 58 to 98) and 2 +/- 3% after the procedure (95 CI -4 to 8). During the initial hospital period and 30 days after CAS, there was one major and two category 2 minor strokes, as well as two category 1 minor strokes (total 30-day stroke rate was 2.9% for treated patients or 2.6% for treated arteries). There were no myocardial infarctions or deaths during or within 30 days of CAS. None of the NASCET-eligible patients had a stroke. At a mean follow-up of 19 +/- 11 months, three patients (2%) had asymptomatic restenosis. No other major strokes or neurologic deaths occurred., Conclusions: Carotid artery stenting is feasible, can be performed even in high-risk patients and is associated with a low restenosis rate.

Objectives: The study evaluated the relationship between light-to-moderate alcohol consumption and prognosis in patients with left ventricular (LV) systolic dysfunction., Background: Although chronic consumption of large amounts of alcohol can lead to cardiomyopathy, the effects of light-to-moderate alcohol consumption in patients with LV dysfunction are unknown., Methods: The relationship between light-to-moderate alcohol consumption and prognosis was assessed in participants in the Studies of Left Ventricular Dysfunction (SOLVD), all of whom had ejection fraction values < or = 0.35. Baseline characteristics and event rates of patients who consumed 1 to 14 drinks per week (light-to-moderate drinkers, n = 2,594) were compared with those of patients who reported no alcohol consumption (nondrinkers, n = 3,719). The association between light-to-moderate alcohol consumption and prognosis was evaluated using Cox proportional hazards analysis, controlling for baseline differences and important covariates., Results: Mortality rates were lower among light-to-moderate drinkers than among nondrinkers (7.2 vs. 9.4 deaths/100 person-years, p < 0.001). Among patients with ischemic LV dysfunction, light-to-moderate alcohol consumption was independently associated with a reduced risk of all-cause mortality (RR [relative risk] 0.85, p = 0.01), particularly for death from myocardial infarction (RR 0.55, p < 0.001). The risks of cardiovascular death, death from progressive heart failure, arrhythmic death, and hospitalization for heart failure were similar for light-to-moderate drinkers and nondrinkers in this group. Among patients with nonischemic LV dysfunction, light-to-moderate alcohol consumption had no significant effect on mortality (RR 0.93, p = 0.5)., Conclusions: Light-to-moderate alcohol consumption is not associated with an adverse prognosis in patients with LV systolic dysfunction, and it may reduce the risk of fatal myocardial infarction in patients with ischemic LV dysfunction.

Objectives: The present analysis examines the prognostic implications of moderate renal insufficiency in patients with asymptomatic and symptomatic left ventricular systolic dysfunction., Background: Chronic elevations in intracardiac filling pressures may lead to progressive ventricular dilation and heart failure progression. The ability to maintain fluid balance and prevent increased intracardiac filling pressures is critically dependent on the adequacy of renal function., Methods: This is a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) Trials, in which moderate renal insufficiency is defined as a baseline creatinine clearance <60 ml/min, as estimated from the Cockroft-Gault equation., Results: In the SOLVD Prevention Trial, multivariate analyses demonstrated moderate renal insufficiency to be associated with an increased risk for all-cause mortality (Relative Risk [RR] 1.41; p = 0.001), largely explained by an increased risk for pump-failure death (RR 1.68; p = 0.007) and the combined end point death or hospitalization for heart failure (RR 1.33; p = 0.001). Likewise, in the Treatment Trial, multivariate analyses demonstrated moderate renal insufficiency to be associated with an increased risk for all-cause mortality (RR 1.41; p = 0.001), also largely explained by an increased risk for pump-failure death (RR 1.49; p = 0.007) and the combined end point death or hospitalization for heart failure (RR 1.45; p = 0.001)., Conclusions: Even moderate degrees of renal insufficiency are independently associated with an increased risk for all-cause mortality in patients with heart failure, largely explained by an increased risk of heart failure progression. These data suggest that, rather than simply being a marker of the severity of underlying disease, the adequacy of renal function may be a primary determinant of compensation in patients with heart failure, and therapy capable of improving renal function may delay disease progression.

beta-Blockers have emerged as an important therapy in patients with symptomatic left ventricular systolic dysfunction. Early studies demonstrated that beta-blocker therapy improved left ventricular function, reduced neurohumoral activity and reduced heart failure symptoms in these patients. While none of these small studies demonstrated a significant benefit in terms of overall survival, several meta-analyses suggested that beta-blocker therapy could, in fact, reduce mortality in patients with left ventricular systolic dysfunction and mild to moderate heart failure symptoms (New York Heart Association class II or III). Three large, recently completed, trials have confirmed the benefit of beta-blockade in these patients. This report reviews some of the initial clinical studies of beta-blockade in heart failure, examines the findings of the three large multicentre trials and other relevant research. Finally, ongoing trials designed to assess the relative efficacy of different beta-blockers and evaluate the utility of beta-blockade in specific subsets of patients with heart failure are discussed.

Objectives: We sought to assess the effect of baseline ejection fraction on survival difference between patients with life-threatening ventricular arrhythmias who were treated with an antiarrhythmic drug (AAD) or implantable cardioverter-defibrillator (ICD)., Background: The Antiarrhythmics Versus Implantable Defibrillators (AVID) study demonstrated improved survival in patients with ventricular fibrillation or ventricular tachycardia with a left ventricular ejection fraction (LVEF) < or =0.40 or hemodynamic compromise., Methods: Survival differences between AAD-treated and ICD-treated patients entered into the AVID study (patients presenting with sustained ventricular arrhythmia associated with an LVEF < or =0.40 or hemodynamic compromise) were compared at different levels of ejection fraction., Results: In patients with an LVEF > or =0.35, there was no difference in survival between AAD-treated and ICD-treated patients. A test for interaction was not significant, but had low power to detect an interaction. For patients with an LVEF 0.20 to 0.34, there was a significantly improved survival with ICD as compared with AAD therapy. In the smaller subgroup with an LVEF <0.20, the same magnitude of survival difference was seen as that in the 0.20 to 0.34 LVEF subgroup, but the difference did not reach statistical significance., Conclusions: These data suggest that patients with relatively well-preserved LVEF (> or =0.35) may not have better survival when treated with the ICD as compared with AADs. At a lower LVEF, the ICD appears to offer improved survival as compared with AADs. Prospective studies with larger patient numbers are needed to assess the effect of relatively well-preserved ejection fraction (> or =0.35) on the relative treatment effect of AADs and the ICDs.

Background-Treatment with diuretics has been reported to increase the risk of arrhythmic death in patients with hypertension. The effect of diuretic therapy on arrhythmic death in patients with left ventricular dysfunction is unknown. Methods and Results-We conducted a retrospective analysis of 6797 patients with an ejection fraction <0.36 enrolled in the Studies Of Left Ventricular Dysfunction (SOLVD) to assess the relation between diuretic use at baseline and the subsequent risk of arrhythmic death. Participants receiving a diuretic at baseline were more likely to have an arrhythmic death than those not receiving a diuretic (3.1 vs 1.7 arrhythmic deaths per 100 person-years, P=0.001). On univariate analysis, diuretic use was associated with an increased risk of arrhythmic death (relative risk [RR] 1.85, P=0.0001). After controlling for important covariates, diuretic use remained significantly associated with an increased risk of arrhythmic death (RR 1.37, P=0.009). Only non-potassium-sparing diuretic use was independently associated with arrhythmic death (RR 1.33, P=0.02). Use of a potassium-sparing diuretic, alone or in combination with a non-potassium-sparing diuretic, was not independently associated with an increased risk of arrhythmic death (RR 0.90, P=0.6). Conclusions-In SOLVD, baseline use of a non-potassium-sparing diuretic was associated with an increased risk of arrhythmic death, whereas baseline use of a potassium-sparing diuretic was not. These data suggest that diuretic-induced electrolyte disturbances may result in fatal arrhythmias in patients with systolic left ventricular dysfunction.

Increased arterial stiffness results in increased characteristic impedance of the aorta and increased pulse wave velocity, which increases systolic and pulse pressures. An association between increased pulse pressure and adverse cardiovascular events has been found in normotensive and hypertensive patient populations. Increased pulse pressure has also been associated with thickening of the carotid intima and media. However, the relationship between pulse pressure and stroke has not previously been evaluated. In this study, we examined the hypothesis that pulse pressure is an independent predictor of stroke in elderly patients with systolic hypertension entered in the Systolic Hypertension in the Elderly Program. Differences in baseline characteristics were examined by tertiles of pulse pressure. The independent prognostic value of pulse pressure and mean arterial pressure for predicting either stroke or total mortality was assessed with Cox proportional hazards models that included pulse pressure, mean arterial pressure, and other variables that were significant on univariate analysis. This analysis demonstrated an 11% increase in stroke risk and a 16% increase in risk of all-cause mortality for each 10-mm Hg increase in pulse pressure. Each 10-mm Hg increase in mean arterial pressure was independently associated with a 20% increase in the risk of stroke and a 14% increase in the risk of all-cause mortality. These data provide strong evidence of an association of increased conduit vessel stiffness, as indicated by increased pulse pressure, with stroke and total mortality, independent of the effects of mean arterial pressure, in elderly patients with isolated systolic hypertension.

Left ventricular (LV) systolic dysfunction, as indicated by a reduced LV ejection fraction (EF) is a potent predictor of cardiovascular mortality. Radionuclide angiography accurately and reproducibly assesses LVEF; however, echocardiography is used more frequently in clinical practice. Whether these methods predict similar mortality has not been fully investigated. We performed a retrospective analysis of patients with baseline radionuclide angiographic (RNA; n = 4,330) and echocardiographic (echo; n = 1,376) based EFs < or =0.35 who were enrolled in the Studies Of Left Ventricular Dysfunction (SOLVD) to address this hypothesis. After adjusting for important prognostic variables, the risk of death (RR 1.15; 95% confidence interval 1.01 to 1.30; p = 0.03) and of cardiovascular death (RR 1.15; 95% confidence interval 1.01 to 1.32; p = 0.04) was higher for patients with ECG-based EFs. To compare the 2 techniques across a range of EF values, we divided the cohort into tertiles of EF. The adjusted risk estimates for all-cause and cardiovascular mortality were similar within each tertile. Of note, the mortality difference in patients with echo- versus RNA-based EFs was most prominent in women. Further, patients with echo-based EFs had significantly higher mortality at sites where this technique was less frequently used to assess the EF. Thus, for a given EF < or =0.35, an echo-based value was associated with a higher risk of death compared with the RNA-based method of measurement. These data suggest that EF values determined by echocardiography and radionuclide angiography predict different mortality and this may, in part, be related to technical proficiency as well as patient characteristics.

We conducted a retrospective analysis of the Studies Of Left Ventricular Dysfunction (SOLVD) trials to assess the predictive value of the baseline white blood cell (WBC) count on mortality. Mortality was higher in participants with a baseline WBC count >7,000 compared to those with a baseline WBC < or =7,000 (27% vs 21%, p <0.0001). After controlling for important covariates, each increase in WBC count of 1,000/mm3 was significantly associated with an increased risk of all-cause mortality (relative risk [RR] 1.05, p <0.001). Overall, compared with a baseline WBC count < or =7,000, a baseline WBC count >7,000 was significantly associated with an increased risk of all-cause mortality (RR 1.22, p = 0.001). In participants with ischemic left ventricular (LV) dysfunction, a WBC count >7,000 remained significantly associated with an increased risk of all-cause mortality (RR 1.26, p <0.001), whereas in participants with nonischemic LV dysfunction there was no relation between WBC count and mortality (RR 1.08, p = 0.5). Thus, baseline WBC is an independent predictor of mortality in patients with LV dysfunction, specifically in those with ischemic cardiomyopathy.

Objectives: The purpose of this study was to evaluate the relationship of baseline pulse pressure and mean arterial pressure to mortality in patients with left ventricular dysfunction., Background: Increased conduit vessel stiffness increases pulse pressure and pulsatile load, potentially contributing to adverse outcomes in patients with left ventricular dysfunction., Methods: Pulse and mean arterial pressure were analyzed for their effect on mortality, adjusting for other modifiers of risk, using Cox proportional hazards regression analysis of data collected from 6,781 patients randomized into the Studies of Left Ventricular Dysfunction trials., Results: Pulse and mean arterial pressure were related positively to each other, age, ejection fraction and prevalence of diabetes and hypertension and inversely to prior myocardial infarction and beta-adrenergic blocking agent use. Higher pulse pressure was associated with increased prevalence of female gender, greater calcium channel blocking agent, digoxin and diuretic use, lower heart rate and a higher rate of reported smoking history. Higher mean arterial pressure was associated with higher heart rate, lower calcium channel blocker and digoxin use and lower New York Heart Association functional class. Over a 61-month follow-up 1,582 deaths (1,397 cardiovascular) occurred. In a multivariate analysis adjusting for the above covariates and treatment assignment, higher pulse pressure remained an independent predictor of total and cardiovascular mortality (total mortality relative risk, 1.05 per 10 mm Hg increment; 95% confidence interval, 1.01 to 1.10; p = 0.02). Mean arterial pressure was inversely related to total and cardiovascular mortality (total mortality relative risk, 0.89; 95% confidence interval, 0.85 to 0.94; p <0.0001)., Conclusions: One noninvasive blood pressure measurement provides two independent prognostic factors for survival. Increased conduit vessel stiffness, as assessed by pulse pressure, may contribute to increased mortality in patients with left ventricular dysfunction, independent of mean arterial pressure.

Objectives: This analysis was performed to assess whether beta-adrenergic blocking agent use is associated with reduced mortality in the Studies of Left Ventricular Dysfunction (SOLVD) and to determine if this relationship is altered by angiotensin-converting enzyme (ACE) inhibitor use., Background: The ability of beta-blockers to alter mortality in patients with asymptomatic left ventricular dysfunction is not well defined. Furthermore, the effect of beta-blocker use, in addition to an ACE inhibitor, on these patients has not been fully addressed., Methods: This retrospective analysis evaluated the association of baseline beta-blocker use with mortality in 4,223 mostly asymptomatic Prevention trial patients, and 2,567 symptomatic Treatment trial patients., Results: The 1,015 (24%) Prevention trial patients and 197 (8%) Treatment trial patients receiving beta-blockers had fewer symptoms, higher ejection fractions and different use of medications than patients not receiving beta-blockers. On univariate analysis, beta-blocker use was associated with significantly lower mortality than nonuse in both trials. Moreover, a synergistic reduction in mortality with use of both a beta-blocker and enalapril was suggested in the Prevention trial. After adjusting for important prognostic variables with Cox multivariate analysis, the association of beta-adrenergic blocking agent use with reduced mortality remained significant for Prevention trial patients receiving enalapril. Lower rates of arrhythmic and pump failure death and risk of death or hospitalization for heart failure were observed., Conclusions: The combination of a beta-blocker and enalapril was associated with a synergistic reduction in the risk of death in the SOLVD Prevention trial.

Unlabelled: Estimate the effect of angiotensin converting enzyme (ACE) inhibitors on the risk of sudden cardiac death (SCD) following myocardial infarction (MI)., Background: Trials in post-MI patients have shown that ACE inhibitor therapy reduces mortality. However, the effect on SCD as a mechanism has not been clarified., Methods: Trials of ACE inhibitor therapy following MI reported between January, 1978 and August, 1997 were identified. Studies were included if they met the following criteria: 1) randomized comparison of ACE inhibitor to placebo within 14 days of MI; 2) study duration/blinded follow-up of > or =6 weeks; 3) the number of deaths and modes of death were reported or could be obtained from the investigators., Results: We identified 374 candidate articles, of which 15 met the inclusion criteria. The 15 trials included 15,104 patients, 2,356 of whom died. Most (87%) fatalities were cardiovascular and 900 were SCDs. A significant reduction in SCD risk or a trend towards this was observed in all of the larger (N > 500) trials. Overall, ACE inhibitor therapy resulted in significant reductions in risk of death (random effects odds ratio [OR] = 0.83; 95% confidence interval [CI] 0.71-0.97), cardiovascular death (OR = 0.82; 95% CI 0.69-0.97) and SCD (OR = 0.80; 95% CI 0.70-0.92)., Conclusions: This analysis is consistent with prior reports showing that ACE inhibitors decrease the risk of death following a recent MI by reducing cardiovascular mortality. Moreover, this analysis suggests that a reduction in SCD risk with ACE inhibitors is an important component of this survival benefit.

A substantial number of patients present with medically refractory angina who are not candidates for angioplasty or bypass surgery. The creation of channels between the myocardium and the ventricular blood pool has been performed after thoracotomy with excellent relief of symptoms but has been associated with high perioperative mortality. We investigated the safety of a nonoperative, percutaneous technique for channel creation. Twenty-seven patients with angina and coronary anatomy not amenable to revascularization with coronary angioplasty or bypass surgery underwent percutaneous transluminal myocardial revascularization (PTMR). Energy from a Holmium:yttrium-aluminum-garnet (YAG) laser was directed through a fiber enclosed in a catheter to the ventricular myocardium creating channels between the blood pool and the myocardium. On average, 17 +/- 4 channels were formed per patient. There were no procedure-related deaths, episodes of tamponade, or other complications except for an increase in creatine phosphokinase in 1 patient. Immediately after the procedure, there was no worsening of regional wall motion function in any patient, but rather improvement in some. All patients were discharged alive after a hospital stay of 1.8 +/- 1.5 days. Mean Canadian Cardiovascular Society functional class declined from 3.6 +/- 0.5 before the procedure to 0.65 +/- 0.8 at 30 days after the procedure (p < 0.01). For 12 patients eligible for 6-month follow-up, mean functional class was 0.94 +/- 0.97. At 6-month stress testing, 9 of these 12 had no electrocardiographic evidence of ischemia. Thus, PTMR can be performed safely in the cardiac catheterization laboratory with a complication rate lower than that reported in surgical series and with excellent near-term symptomatic relief. The long-term effect of PTMR on mortality and relief of angina as well as its safety and effectiveness compared with the surgical approach remains to be defined.

Objective: This study undertook to determine if the presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular dysfunction was associated with increased mortality and, if so, whether the increase could be attributed to progressive heart failure or arrhythmic death., Background: Atrial fibrillation is a common condition in heart failure with the potential to impact hemodynamics and progression of left ventricular systolic dysfunction as well as the electrophysiologic substrate for arrhythmias. The available data do not conclusively define the effect of atrial fibrillation on prognosis in heart failure., Methods: A retrospective analysis of the Studies of Left Ventricular Dysfunction Prevention and Treatment Trials was conducted that compared patients with atrial fibrillation to those in sinus rhythm at baseline for the risk of all-cause mortality, progressive pump-failure death and arrhythmic death., Results: The patients with atrial fibrillation at baseline, compared to those in sinus rhythm, had greater all-cause mortality (34% vs. 23%, p < 0.001), death attributed to pump-failure (16.7% vs. 9.4%, p < 0.001) and were more likely to reach the composite end point of death or hospitalization for heart failure (45% vs. 33%, p < 0.001), but there was no significant difference between the groups in arrhythmic deaths. After multivariate analysis, atrial fibrillation remained significantly associated with all-cause mortality (relative risk [RR] 1.34, 95% confidence interval [CI] 1.12 to 1.62, p=0.002), progressive pump-failure death (RR 1.42, 95% CI 1.09 to 1.85, p=0.01), the composite end point of death or hospitalization for heart failure (RR 1.26, 95% CI 1.03 to 1.42, p=0.02), but not arrhythmic death (RR 1.13; 95% CI 0.75 to 1.71; p=0.55)., Conclusions: The presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular systolic dysfunction is associated with an increased risk for all-cause mortality, largely explained by an increased risk for pump-failure death. These data suggest that atrial fibrillation is associated with progression of left ventricular systolic dysfunction.

The aim of the present study was to develop a new noninvasive approach for the assessment of regional and global myocardial contractility without the need for pharmacological intervention to alter load. Thirty-four healthy adults and five adults with dilated cardiomyopathy (DCM) were studied. Patients with diabetes mellitus and hyperthyroidism were eliminated from the study. The remainder underwent echocardiography, sphygmomanometric blood pressure determination, and carotid pulse tracings. Left ventricular cross section in the parasternal long-axis four- and two-chamber views was divided into 20 segments. Associated measurements of end-systolic pressure and left ventricular ejection time enabled shortening, shortening rate, and ejection fraction/afterload relationships to be determined. A discriminant analysis showed that the ejection fraction/afterload relationship in patients with DCM differed substantially from that of control subjects and was the most sensitive in this regard. Endocardial shortening, mid-wall shortening, and ejection fraction/afterload relationships demonstrated linearity or nonlinearity for control subjects. This study thus permits the assessment of contractility in individual subjects without the need for drug interventions because load alteration stems from the variation of wall stress from base to apex in the left ventricle. More importantly, the approach may be applied to patients with segmental abnormalities of contractile function.

Purpose: To evaluate long-term survivors of high-grade non-Hodgkin's lymphomas (NHLs) for late effects and to attempt to assess the relative contributions of the primary treatment modalities to these late effects., Patients and Methods: Of 103 young survivors followed up for 1 to 20 years, 74 patients were interviewed and underwent various investigations, and an additional 12 patients were interviewed only. Of the 86 patients, 65 had previously suffered from small non-cleaved-cell lymphoma, 16 from lymphoblastic lymphoma, and five from large-cell lymphoma., Results: Left ventricular dysfunction was identified in eight of 57 (14.0%) patients who had received doxorubicin (DOX) in doses greater than 200 mg/m2, of whom four were symptomatic and four were asymptomatic. A ninth patient required a pacemaker. Of the 86 patients, 23 (26.7%) reported pregnancies, 18 of whom had 30 children. Two of the 86 (2.3%) patients developed second cancers. Other major late effects included posttransfusion viral hepatitis, eight patients; CNS toxicity, two patients; endocrine impairment, 14 patients; vitamin B12 deficiency, two patients; esophageal stricture, one patient; urinary tract problems, two patients; and musculoskeletal defects, three patients. Major late effects occurred in 11 of 21 (52.4%) patients who had received radiation as well as chemotherapy, eight of 22 (36.4%) patients who had surgical resections as well as chemotherapy, and 17 of 74 (23.0%) patients who had received chemotherapy alone., Conclusion: The predominant major late effects observed were late cardiac toxicity related to DOX therapy and hepatitis C virus infection that presumably resulted from blood product transfusions administered before the introduction of screening for the hepatitis C virus. Fertility was not greatly impaired, and second malignancies were uncommon. No patient had clinically significant impairment of growth. Radiation appeared to increase the likelihood of late effects.

This report summarizes the clinical and socioeconomic characteristics of the first 542 patients entered into the Antiarrhythmics Versus Implantable Defibrillator (AVID) trial. AVID is a multicenter trial comparing a strategy of initial implantable cardioverter-defibrillator placement to initial antiarrhythmic drug therapy in preventing death in patients resuscitated from cardiac arrest who were not taking amiodarone and who did not have an implantable cardioverter-defibrillator in place at the time of the index event. These patients were randomly assigned to immediate defibrillator placement or to "best" medical therapy. Clinical and socioeconomic histories were collected by interview using standard terms developed for the study. Patients without (group 1) and with (group 2) a history of prior cardiac arrest were compared. The mean age of the 542 patients was 65 +/- 10 years, most were men, white, had coronary disease, and were highly functional despite the fact that only a minority were employed. Almost all had some form of health insurance. At the time of the index event, few were taking any therapy to prevent cardiac arrest, even in the group of patients with a history of previous cardiac arrest. Thus, the clinical and socioeconomic profile of patients resuscitated from sudden cardiac death entered into the AVID study is generally as expected. There is a striking absence of any attempt at chronic therapy to prevent cardiac arrest in most patients with a prior ventricular tachycardia or ventricular fibrillation.

Data from epidemiologic, autopsy, Holter monitoring, and electrophysiologic studies support the hypothesis that acute myocardial ischemia, even in the absence of myocardial infarction, is a critical component of the pathophysiology of sudden coronary death. Acute myocardial ischemia superimposed upon ventricles damaged from previous infarctions has been demonstrated to enhance the generation of lethal ventricular arrhythmias. This is a retrospective analysis of 6,797 participants in the Studies of Left Ventricular Dysfunction prevention and treatment trials. Both univariate and multivariate Cox proportional-hazards modeling were used to study the association of anticoagulant and antiplatelet therapy with the risk for sudden cardiac death. The following covariates were adjusted for in the analysis: age, ejection fraction, gender, atrial fibrillation, diabetes, a history of angina, prior infarction, prior revascularization, and the regular use of beta blockers, diuretics, digoxin, antiarrhythmic agents, or enalapril. The overall incidence of sudden cardiac death per 100 patient-years of follow-up was 2.24%. In multivariate analysis, antiplatelet and anticoagulant monotherapy each remained independently associated with a reduction in the risk of sudden cardiac death: antiplatelet therapy with a 24% reduction (relative risk [RR] 0.76; 95% confidence interval [CI] 0.61-0.95) and antiplatelet monotherapy with a 32% reduction (RR 0.68; 95% CI 0.48-0.96). Thus, in patients with moderate to severe left ventricular systolic dysfunction resulting from coronary artery disease, antiplatelet and anticoagulant therapy are each associated with a reduction in the risk of sudden cardiac death.

Objectives: The aims of this study were to describe the incidence and spectrum of thromboembolic events experienced by patients with moderate to severe left ventricular systolic dysfunction in normal sinus rhythm and to study the association between ejection fraction and thromboembolic risk., Background: The annual incidence of thromboembolic events in patients with heart failure is estimated to range from 0.9% to 5.5%. Previous studies demonstrating a relation between worsening left ventricular systolic function and thromboembolic risk are difficult to interpret because of the prevalence of atrial fibrillation, an independent risk factor for thromboembolism, in the patients with a lower ejection fraction., Methods: This is a retrospective analysis of the Studies of Left Ventricular Dysfunction prevention and treatment trials data base. Patients with atrial fibrillation were excluded, resulting in 6,378 participants in sinus rhythm at the time of randomization. Thromboembolic events include strokes, pulmonary emboli and peripheral emboli. Separate analyses were conducted in each gender because there was evidence of a significant interaction between ejection fraction and gender on the risk of thromboembolic events (p = 0.04)., Results: The overall annual incidence of thromboembolic events was 2.4% in women and 1.8% in men. On univariate analysis, a decline in ejection fraction was [corrected] associated with thromboembolic risk in women (relative risk [RR] per 10% decrease in ejection fraction 1.58, 95% confidence interval [CI] 1.10 to 2.26, p = 0.01), but not in men. On multivariate analysis, a decline in ejection fraction remained independently associated with thromboembolic risk in women (RR per 10% decrease 1.53, 95% CI 1.06 to 2.20, p = 0.02), but no relation was demonstrated in men., Conclusions: In patients with left ventricular systolic dysfunction and sinus rhythm, the annual incidence of thromboembolic events is low. Ejection fraction appears to be independently associated with thromboembolic risk in women, but not in men.

A number of studies that assessed myocardial contractility by noninvasive means have been conducted in the past. However, many of these studies are limited because they assessed the velocity of fiber shortening-afterload relationship at only a single location in the ventricle, thus assuming uniform contractility throughout the ventricle. This is often not the case, particularly in patients with coronary disease. The present study provides a new approach to assessing regional and global function that will be applicable to patients with nonuniform contractile function and makes use of entirely noninvasively obtained data. In addition, the method proposed will permit the question of linearity or nonlinearity of shortening rate-afterload relationship to be addressed in a more detailed, quantitative manner.

Objectives: Human immunodeficiency virus (HIV) infection in children can be complicated by the development of cardiac disease. Decreased left ventricular function has been temporally associated with the use of zidovudine (azidothymidine; AZT) in adults with HIV and has been associated with changes in cardiac muscle mitochondria in animal models. This study was done in an attempt to determine whether the cardiac disease is related to the antiretroviral therapy or to progressive HIV infection., Methods: We retrospectively reviewed echocardiograms, clinical records, and laboratory data from 137 HIV-infected children who were being treated by the Pediatric Branch, National Cancer Institute, and who were receiving AZT or didanosine, both drugs, or no antiretroviral therapy., Results: Despite correction of the echocardiographic results for HIV disease severity with markers such as CD4+ lymphocyte count, time since infection, mode of acquisition of HIV, and age, children who were treated with AZT had a lower average fractional shortening than those who were not treated with AZT (p < 0.00001). There was a nonlinear relation between days of AZT use and this There was a nonlinear relation between days of AZT use and this decrease in fractional shortening. The odds that a cardiomyopathy would develop was 8.4 times greater in children who had previously used AZT than in those who had never taken AZT (95% confidence interval, 1.7 to 42.0). Didanosine was not associated with the development of a cardiomyopathy., Conclusions: Treatment of HIV-infected children with AZT may be associated with the development of a cardiomyopathy; didanosine does not appear to increase the risk of cardiomyopathy. The continued use of AZT in a child in whom a cardiomyopathy develops should be carefully assessed, and all children receiving AZT should be followed by serial cardiac examination and echocardiograms.

The goal of radiofrequency catheter ablation and the criterion for efficacy is the elimination of arrhythmogenic myocardium. The application of radiofrequency current in the heart clearly results in lower morbidity and mortality rates than thoracic and cardiac surgical procedures in general, and comparisons of therapy with radiofrequency catheter ablation and therapy with thoracic and cardiac surgical procedures in randomized clinical trials are unwarranted. Trials of radiofrequency catheter ablation versus medical or implantable cardioverter defibrillator therapy may be indicated in certain conditions, such as ventricular tachycardia associated with coronary artery disease. Randomized trials are recommended for new and radical departures in technology that aim to accomplish the same goals as radiofrequency catheter ablation. Surveillance using registries and/or databases is necessary in the assessment of long-term safety and efficacy.

The goal of radiofrequency catheter ablation and the criterion for efficacy is the elimination of arrhythmogenic myocardium. The application of radiofrequency current in the heart clearly results in lower morbidity and mortality rates than thoracic and cardiac surgical procedures in general, and comparisons of therapy with radiofrequency catheter ablation and therapy with thoracic and cardiac surgical procedures in randomized clinical trials is unwarranted. Trials of radiofrequency catheter ablation versus medical or implantable cardioverter-defibrillator therapy may be indicated in certain conditions, such as ventricular tachycardia associated with coronary artery disease. Randomized trials are recommended for new and radical departures in technology that aim to accomplish the same goals as radiofrequency catheter ablation. Surveillance using registries and/or databases is necessary in the assessment of long-term safety and efficacy.

The Antiarrhythmics Versus Implantable Defibrillators (AVID) study compares a strategy of initial treatment with an implantable cardioverter-defibrillator (ICD) to a strategy of initial treatment with an antiarrhythmic drug to prevent death in patients with a history of ventricular fibrillation or hemodynamically compromising ventricular tachycardia, or both. Neither arrhythmia can have been due to a transient or correctable cause. The principle exclusions are a contraindication to amiodarone therapy and inability to undergo ICD implantation. Antiarrhythmic drug therapy includes empiric amiodarone and guided sotalol. The ICDs allowed are advanced generation devices, and most are implanted transvenously. The primary end point of the study is total mortality. Secondary end points are cost and quality of life. The study was designed in 2 phases. The pilot phase enrolled 200 patients between June 1993 and June 1994. Data collected during the pilot phase confirmed that the trial is feasible. An additional 1,000 patients will be enrolled between June 1994 and March 1997. It is anticipated that all 1,200 patients will be followed until September 1998, and will be included in the intention-to-treat analysis.

In this summary, the authors provide the background of and proposed protocol for a clinical evaluation of the safety and efficacy of the Novacor N120 Left Ventricular Assist System, sponsored by the National Heart, Lung, and Blood Institute. Although the clinical trial was never carried out, the protocol developed for this trial may be useful to other investigators considering a clinical trial of a circulatory support device. The protocol is summarized here and in five more detailed articles in this issue.

Left ventricular rupture resulting in death has been reported to be a complication of percutaneous mitral commissurotomy. We report a 71-year-old man in whom a left ventricular rupture occurred during percutaneous mitral commissurotomy and resulted in hemodynamic collapse due to acute cardiac tamponade. The patient was stabilized using percutaneously instituted cardiopulmonary bypass support with subsequent repair of the left ventricle and successful mitral valve replacement. Three months later this patient remains in New York Heart Class I.

A safe and easily applied technique of percutaneous cardiopulmonary bypass support has been developed for use in the cardiac catheterization laboratory. The importance of this technique lies in its ability to maintain hemodynamic stability during high risk interventional procedures regardless of intrinsic cardiac function. Venous and arterial cannulas (18F) are inserted percutaneously over a stiff guide wire after sequential dilatation with 12F and 14F dilators. Bypass flow rates of up to 5 L/min can be achieved. This technique can be applied to support patients with cardiac arrest, hemodynamic collapse after abrupt closure during coronary angioplasty, and cardiogenic shock, as well as those undergoing high-risk elective coronary angioplasty. This form of support also permits transport of the patient to the operating room in a stable condition after an unsuccessful angioplasty. The complications are mostly related to cannula removal and can be minimized by the use of a proper technique. Although the ultimate role of this new technique remains to be completely defined, it appears that it will expand the patient population for whom coronary interventions can be applied.