Outcomes after emergency department discharge with a primary diagnosis of heart failure.

BACKGROUND: Patients with decompensated chronic heart failure (CHF) are frequently evaluated in emergency departments (ED). The outcomes of such patients after discharge to the outpatient setting from the ED are not well known. Risk factors for return ED visits or subsequent hospital admission after ED discharge for CHF also are not known. METHODS: Charts were reviewed from all 112 patients discharged from the Parkland Memorial Hospital ED with a primary diagnosis of CHF from October to December 1998. A composite end point ("failure of outpatient therapy") was prespecified to be a recurrent ED visit for CHF, hospitalization for CHF, or death at 3 months after the index ED discharge. RESULTS: Within 3 months of the index ED visit, 61% of the study population met the composite end point. The median time to failure of outpatient therapy was 30 days. Univariate analysis of 27 clinical and demographic variables demonstrated the respiratory rate at presentation as the only predictor of failure of outpatient therapy (P =.02). Multivariate analysis of a model with 8 prespecified variables also demonstrated respiratory rate to be the only variable independently associated with an increased risk for the composite end point (odds ratio 1.6, 95% confidence interval 1.1-2.6, for each increase of 5 breaths/min). CONCLUSION: There is a high rate of failure of outpatient therapy (61%) in patients discharged with a primary diagnosis of CHF from an urban county hospital ED. Increased respiratory rate on presentation to the ED may be associated with adverse outcomes after ED discharge for CHF.

Prognostic importance of elevated jugular venous pressure and a third heart sound in patients with heart failure.

BACKGROUND: The independent prognostic value of elevated jugular venous pressure or a third heart sound in patients with heart failure is not well established. METHODS: We performed a retrospective analysis of the Studies of Left Ventricular Dysfunction treatment trial, in which 2569 patients with symptomatic heart failure or a history of it were randomly assigned to receive enalapril or placebo. The mean (+/-SD) follow-up was 32+/-15 months. The presence of elevated jugular venous pressure or a third heart sound was ascertained by physical examination on entry into the trial. The risks of hospitalization for heart failure and progression of heart failure as defined by death from pump failure and the composite end point of death or hospitalization for heart failure were compared in patients with these findings on physical examination and patients without these findings. RESULTS: Data on 2479 patients were complete and analyzed. In multivariate analyses that were adjusted for other markers of the severity of heart failure, elevated jugular venous pressure was associated with an increased risk of hospitalization for heart failure (relative risk, 1.32; 95 percent confidence interval, 1.08 to 1.62; P<0.01), death or hospitalization for heart failure (relative risk, 1.30; 95 percent confidence interval, 1.11 to 1.53; P<0.005), and death from pump failure (relative risk, 1.37; 95 percent confidence interval, 1.07 to 1.75; P<0.05). The presence of a third heart sound was associated with similarly increased risks of these outcomes. CONCLUSIONS: In patients with heart failure, elevated jugular venous pressure and a third heart sound are each independently associated with adverse outcomes, including progression of heart failure. Clinical assessment for these findings is currently feasible and clinically meaningful.

Prognostic impact of diabetes mellitus in patients with heart failure according to the etiology of left ventricular systolic dysfunction.

OBJECTIVES: We sought to determine the relative impact of diabetes mellitus on prognosis in ischemic compared with nonischemic cardiomyopathy. BACKGROUND: Ischemic myocardium is characterized by increased reliance on aerobic and anaerobic glycolysis. Because glucose utilization by cardiomyocytes is an insulin-mediated process, we hypothesized that diabetes would have a more adverse impact on mortality and progression of heart failure in ischemic compared with nonischemic cardiomyopathy. METHODS: We performed a retrospective analysis of the Studies Of Left Ventricular Dysfunction (SOLVD) Prevention and Treatment trials. RESULTS: In adjusted analyses, diabetes mellitus was strongly associated with an increased risk for all-cause mortality in patients with ischemic cardiomyopathy, (relative risk [RR] 1.37, 95% confidence interval [CI] 1.21 to 1.55; p < 0.0001), but not in those with nonischemic cardiomyopathy (RR 0.98, 95% CI 0.76 to 1.32; p = 0.98). The increased mortality in patients with ischemic cardiomyopathy compared with nonischemic cardiomyopathy was limited to those with ischemic cardiomyopathy and diabetes mellitus (RR 1.37, 95% CI 1.21 to 1.56; p < 0.0001). When patients with ischemic cardiomyopathy and diabetes mellitus were excluded, there was no significant difference in mortality risk between the ischemic and nonischemic cardiomyopathy groups after adjusted analysis (RR 0.99, 95% CI 0.86 to 1.15; p = 0.99). Previous surgical revascularization identified patients within the cohort with ischemic cardiomyopathy and diabetes mellitus, with improved prognosis. CONCLUSIONS: The differential impact of diabetes on mortality and heart failure progression according to the etiology of heart failure suggests that diabetes and ischemic heart disease interact to accelerate the progression of myocardial dysfunction. Evaluation of the potential for revascularization may be particularly important in patients with ischemic cardiomyopathy and diabetes mellitus.

Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction.

BACKGROUND: Black patients with heart failure have a poorer prognosis than white patients, a difference that has not been adequately explained. Whether racial differences in the response to drug treatment contribute to differences in outcome is unclear. To address this issue, we pooled and analyzed data from the Studies of Left Ventricular Dysfunction (SOLVD) prevention and treatment trials, two large, randomized trials comparing enalapril with placebo in patients with left ventricular dysfunction. METHODS: We used a matched-cohort design in which up to four white patients were matched with each black patient according to trial, treatment assignment, sex, left ventricular ejection fraction, and age. A total of 1196 white patients (580 from the prevention trial and 616 from the treatment trial) were matched with 800 black patients (404 from the prevention trial and 396 from the treatment trial). The average duration of follow-up was 35 months in the prevention trial and 33 months in the treatment trial. RESULTS: The black patients and the matched white patients had similar demographic and clinical characteristics, but the black patients had higher rates of death from any cause (12.2 vs. 9.7 per 100 person-years) and of hospitalization for heart failure (13.2 vs. 7.7 per 100 person-years). Despite similar doses of drug in the two groups, enalapril therapy, as compared with placebo, was associated with a 44 percent reduction (95 percent confidence interval, 27 to 57 percent) in the risk of hospitalization for heart failure among the white patients (P<0.001) but with no significant reduction among black patients (P=0.74). At one year, enalapril therapy was associated with significant reductions from base line in systolic blood pressure (by a mean [+/-SD] of 5.0+/-17.1 mm Hg) and diastolic blood pressure (3.6+/-10.6 mm Hg) among the white patients, but not among the black patients. No significant change in the risk of death was observed in association with enalapril therapy in either group. CONCLUSIONS: Enalapril therapy is associated with a significant reduction in the risk of hospitalization for heart failure among white patients with left ventricular dysfunction, but not among similar black patients. This finding underscores the need for additional research on the efficacy of therapies for heart failure in black patients.

The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic 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.

Diuretics and risk of arrhythmic death in patients with left ventricular dysfunction.

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.

Beta-adrenergic blocking agent use and mortality in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a post hoc analysis of the Studies of Left Ventricular Dysfunction.

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.

Racial differences in the outcome of left ventricular dysfunction.

BACKGROUND: Population-based studies have found that black patients with congestive heart failure have a higher mortality rate than whites with the same condition. This finding has been attributed to differences in the severity, causes, and management of heart failure, the prevalence of coexisting conditions, and socioeconomic factors. Although these factors probably account for some of the higher mortality due to congestive heart failure among blacks, we hypothesized that racial differences in the natural history of left ventricular dysfunction might also have a role. METHODS: Using data from the Studies of Left Ventricular Dysfunction (SOLVD) prevention and treatment trials, in which all patients received standardized therapy and follow-up, we conducted a retrospective analysis of the outcomes of asymptomatic and symptomatic left ventricular systolic dysfunction among black and white participants. The mean (+/-SD) follow-up was 34.2+/-14.0 months in the prevention trial and 32.3+/-14.8 months in the treatment trial among the black and white participants. RESULTS: The overall mortality rates in the prevention trial were 8.1 per 100 person-years for blacks and 5.1 per 100 person years for whites. In the treatment trial, the rates were 16.7 per 100 person-years and 13.4 per 100 person-years, respectively. After adjustment for age, coexisting conditions, severity and causes of heart failure, and use of medications, blacks had a higher risk of death from all causes in both the SOLVD prevention trial (relative risk, 1.36; 95 percent confidence interval, 1.06 to 1.74; P=0.02) and the treatment trial (relative risk, 1.25; 95 percent confidence interval, 1.04 to 1.50; P=0.02). In both trials blacks were also at higher risk for death due to pump failure and for the combined end point of death from any cause or hospitalization for heart failure, our two predefined indicators of the progression of left ventricular systolic dysfunction. CONCLUSIONS: Blacks with mild-to-moderate left ventricular systolic dysfunction appear to be at higher risk for progression of heart failure and death from any cause than similarly treated whites. These results suggest that there may be racial differences in the outcome of asymptomatic and symptomatic left ventricular systolic dysfunction.

Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD trials. Studies of Left Ventricular Dysfunction.

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.

Adjunctive therapy after reperfusion therapy in acute myocardial infarction.

The current era has witnessed dramatic improvement in the treatment of acute myocardial infarction, due in large part to the more widespread use of thrombolytic therapy aimed at quickly restoring perfusion in the infarct-related artery. This review addresses the role of adjunctive pharmacologic therapy in the thrombolytic era, recognizing that much of the available clinical trial data supporting the role of adjunctive pharmacologic treatment strategies was conducted in patient populations not widely exposed to reperfusion therapy. This review, therefore, explores the data supporting the incremental benefit of therapy with beta blockers, nitrates, angiotensin-converting enzyme inhibitors, or magnesium in addition to thrombolytic therapy. Heparin and aspirin will not be discussed.

Effect of antithrombotic therapy on risk of sudden coronary death in patients with congestive heart failure.

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.

Ejection fraction and risk of thromboembolic events in patients with systolic dysfunction and sinus rhythm: evidence for gender differences in the studies of left ventricular dysfunction trials.

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.