Heart Failure In African Americans Research Articles

CALL ME SENILE NO MORE: AN UNUSUAL CASE OF HEART FAILURE SECONDARY TO CARDIOPULMONARY AMYLOIDOSIS

Amyloidosis causing heart failure in elderly African Americans is often assumed to be senile systemic amyloidosis. A 78-year-old African-American male non-smoker presented with a 1 year history of reduced exercise capacity and 2 months of lower extremity swelling. His medical history included

G-Protein Beta-3 Subunit Genotype Predicts Enhanced Benefit of Fixed-Dose Isosorbide Dinitrate and Hydralazine: Results of A-HeFT

ObjectivesThe purpose of this study was to evaluate the influence of the guanine nucleotide-binding proteins (G-proteins), beta-3 subunit (GNB3) genotype on the effectiveness of a fixed-dose combination of isosorbide dinitrate and hydralazine (FDC I/H) in A-HeFT (African American Heart Failure Trial). BackgroundGNB3 plays a role in alpha2-adrenergic signaling. A polymorphism (C825T) exists, and the T allele is linked to enhanced alpha-adrenergic tone and is more prevalent in African Americans. MethodsA total of 350 subjects enrolled in the genetic substudy (GRAHF [Genetic Risk Assessment of Heart Failure in African Americans]) were genotyped for the C825T polymorphism. The impact of FDC I/H on a composite score (CS) that incorporated death, hospital stay for heart failure, and change in quality of life (QoL) and on event-free survival were assessed in GNB3 genotype subsets. ResultsThe GRAHF cohort was 60% male, 25% ischemic, 97% New York Heart Association functional class III, age 57 ± 13 years, with a mean qualifying left ventricular ejection fraction of 0.24 ± 0.06. For GNB3 genotype, 184 subjects were TT (53%), 137 (39%) CT, and 29 (8%) were CC. In GNB3 TT subjects, FDC I/H improved the CS (FDC I/H = 0.50 ± 1.6; placebo = −0.11 ± 1.8, p = 0.02), QoL (FDC I/H = 0.69 ± 1.4; placebo = 0.24 ± 1.5, p = 0.04), and event-free survival (hazard ratio: 0.51, p = 0.047), but not in subjects with the C allele (for CS, FDC I/H = −0.05 ± 1.7; placebo = −0.09 ± 1.7, p = 0.87; for QoL, FDC I/H = 0.28 ± 1.5; placebo = 0.14 ± 1.5, p = 0.56; and for event-free survival, p = 0.35). ConclusionsThe GNB3 TT genotype was associated with greater therapeutic effect of FDC I/H in A-HeFT. The role of the GNB3 genotype for targeting therapy with FDC I/H deserves further study.

Abstract 315: Anemia predicts 30-Day Hospital Readmission for Heart Failure in African Americans

Background: Anemia is a frequently encountered comorbidity that affects both death and hospitalization in patients with heart failure (HF). The effect of anemia on 30-day hospital readmission in African Americans (AA) with HF has not been studied. Methods: We retrospectively enrolled all 243 (61% female) self-reported AA adults admitted to the University of Illinois at Chicago hospital with the diagnosis of HF from January 2011 to December 2012. Extensive medical chart reviews were performed. Results: The prevalence of anemia with hemoglobin (Hb) <12g/dl was 64.6%. After adjusting for factors known to affect readmission (table), lower Hb (<12g/dl) levels were associated with increased 30-day readmission rates (OR 0.814, 95% CI 1.6-20.7, p=0.008) in a Cox proportional hazard logistic regression model. Conclusion: Lower Hb levels are associated with higher 30-day readmission rates in hospitalized AA patients with HF. Interventions towards appropriate treatment and prevention of anemia in AA with HF might reduce their readmission rates and improve their outcome.

Heart failure in African Americans: disparities can be overcome.

African Americans are disproportionately affected by heart failure, with a high prevalence at an early age. Hypertension, diabetes, obesity, and chronic kidney disease are all common in African Americans and all predispose to heart failure. Neurohormonal imbalances, endothelial dysfunction, genetic polymorphisms, and socioeconomic factors also contribute. In general, the same evidence-based treatment guidelines that apply to white patients with heart failure also apply to African Americans. However, the combination of hydralazine and isosorbide dinitrate is advised specifically for African Americans.

Abstract P113: New-onset Atrial Fibrillation and Risk of Mortality and Cardiovascular Disease in Whites and African Americans: the ARIC Study

Background: Multiple studies have shown that atrial fibrillation (AF), a common cardiac arrhythmia, is associated with increased mortality and higher incidence of stroke and heart failure. However, evidence for this association in African Americans is lacking. Methods: We studied 4,063 African Americans and 11,280 whites in the Atherosclerosis Risk in Communities (ARIC) Study, a US community-based cohort study, aged 45-64 (55% women) and free of AF at baseline in 1987-89. Three additional follow-up exams were conducted in 1990-92, 1993-95, and 1996-98. AF was ascertained during follow-up with study visit ECGs and hospital surveillance. Mortality and incidence of stroke and heart failure were ascertained according to study protocols. Using multivariable Cox proportional hazards models with time-dependent covariates, we calculated hazard ratios (HR) and 95% confidence intervals (CI) of mortality, stroke and heart failure in those with new-onset AF compared to those without AF by race. Results: During an average follow-up of 18 years, 332 AF cases were ascertained in African Americans and 1407 in whites. Overall, African Americans showed higher all-cause mortality and cardiovascular disease rates than whites ( Table ). AF was associated with increased mortality and risk of incident stroke and heart failure in whites and African Americans, even after adjustment for baseline and time-dependent potential confounders ( Table ). Associations of AF with all-cause mortality and stroke were of similar magnitude in both racial groups. However, the association between AF and heart failure was stronger in whites than in African Americans (HR 3.6, 95% CI 3.1-4.2 in whites, vs. HR 2.2, 95% CI 1.6-3.0 in African Americans). Conclusion: New-onset AF was associated with an increased risk of all-cause mortality, stroke, and heart failure in whites and African Americans independently of other cardiovascular risk factors. Table. Hazard ratios (95% confidence interval) of all-cause mortality, stroke, and heart failure in those with new-onset atrial fibrillation (AF) versus those without AF by race, ARIC, 1987-2008 Blacks Whites P for interaction No AF (n=3731) AF (n=332) No AF (n=9873) AF (n=1407) Mortality Deaths (n) 1144 188 2042 630 Person-years 69,483 1268 200,878 7493 Mortality rate 1 18.6 126.3 10.1 62.3 Model 1 1 (ref.) 5.80 (4.93-6.82) 1 (ref.) 4.58 (4.17-5.04) 0.27 Model 2 1 (ref.) 3.20 (2.71-3.76) 1 (ref.) 2.87 (2.61-3.17) 0.68 Stroke Events (n) 281 23 347 64 Person-years 51,082 867 147,608 5040 Incidence rate 1 6.0 25.0 2.4 11.5 Model 1 1 (ref.) 2.91 (1.81-4.68) 1 (ref.) 2.52 (1.86-3.43) 0.94 Model 2 1 (ref.) 1.83 (1.13-2.96) 1 (ref.) 1.91 (1.39-2.62) 0.82 Heart failure Events 613 71 992 364 Person-years 62,570 721 187,847 4578 Incidence rate 1 10.7 108.1 5.3 76.1 Model 1 1 (ref.) 3.35 (2.41-4.65) 1 (ref.) 4.75 (4.09-5.51) 0.02 Model 2 1 (ref.) 2.18 (1.56-3.04) 1 (ref.) 3.63 (3.12-4.21) 0.0006 1 Age- and sex-standardized, per 1000 person-years; Model 1 : Cox proportional hazards model adjusted for age, sex, and study center, with AF incidence as a time-dependent covariate; Model 2 : As model 1, but additionally adjusting for baseline education, and time-dependent body mass index, smoking, diabetes, hypertension, stroke, heart failure, and myocardial infarction Funding(This research has received full or partial funding support from the American Heart Association, National Center)

Abstract MP013: Strong Inverse Relation between Physical Activity and Incidence of Cardiovascular Disease in African Americans: the Atherosclerosis Risk in Communities Study

Introduction: Although there is substantial evidence that physical activity reduces risk of cardiovascular disease (CVD), the few studies that included African Americans offer inconclusive evidence and did not study stroke and heart failure separately. Objective: We examined, in African Americans and Caucasians in the Atherosclerosis Risk in Communities study (ARIC), the association of physical activity with CVD incidence (n=1,039) and its major components - stroke (n=350), heart failure (n=633), and coronary heart disease (n=442) - over a follow-up period of 21 years. Methods: ARIC is a population-based biracial cohort study of 45– to 64-yr-old adults at the baseline visit in 1987–89. Physical activity was assessed using the modified Baecke physical activity questionnaire and categorized by the American Heart Association’s ideal CVD health guidelines: poor, intermediate, and ideal physical activity. An incident CVD event was defined as the first occurrence of 1) heart failure, 2) definite or probable stroke, or 3) coronary heart disease, defined as a definite or probable myocardial infarction or definite fatal coronary heart disease. Results: We included 3,707 African Americans and 10,018 Caucasians free of CVD at the baseline visit. After adjustment for age, sex, cigarette smoking, alcohol intake, hormone therapy use, education, and ‘Western’ and ‘Prudent’ dietary pattern scores, higher physical activity was inversely related to CVD, heart failure, and coronary heart disease incidence in African Americans and Caucasians (p-values for trend tests <.0001), and with stroke in African Americans. Hazard ratios (95% confidence intervals) for CVD for intermediate and ideal physical activity, respectively, compared to poor, were similar by race: 0.65 (0.56, 0.75) and 0.59 (0.49, 0.71) for African Americans, and 0.74 (0.66, 0.83) and 0.67 (0.59, 0.75) for Caucasians (p-value for interaction = 0.38). Physical activity was also associated similarly in African Americans and Caucasians for each of the individual CVD outcomes (coronary heart disease, heart failure, and stroke), with an approximate one-third reduction in risk for intermediate and ideal physical activity versus poor physical activity- this reduction was statistically significant. Conclusions: In conclusion, our findings reinforce public health recommendations that regular physical activity is important for CVD risk reduction, including reductions in stroke and heart failure. They provide strong new evidence that this risk reduction applies to African Americans as well as Caucasians and support the idea that some physical activity is better than none.

The fallacy of racial pharmacogenomics

Personalized pharmacogenomics aims to use individual genotypes to direct medical treatment. Unfortunately, the loci relevant for the pharmacokinetics and especially the pharmacodynamics of most drugs are still unknown. Moreover, we still do not understand the role that individual genotypes play in modulating the pathogenesis, the clinical course and the susceptibility to drugs of human diseases which, although appearing homogeneous on the surface, may vary from patient to patient. To try to deal with this situation, it has been proposed to use interpopulational variability as a reference for drug development and prescription, leading to the development of "race-targeted drugs". Given the present limitations of genomic knowledge and of the tools needed to fully implement it today, some investigators have proposed to use racial criteria as a palliative measure until personalized pharmacogenomics is fully developed. This was the rationale for the FDA approval of BiDil for treatment of heart failure in African Americans. I will evaluate the efficacy and safety of racial pharmacogenomics here and conclude that it fails on both counts. Next I shall review the perspectives and the predicted rate of development of clinical genomic studies. The conclusion is that "next-generation" genomic sequencing is advancing at a tremendous rate and that true personalized pharmacogenomics, based on individual genotyping, should soon become a clinical reality.

Treatment of Heart Failure in African Americans— A Call to Action

Advances in heart failure treatment have not necessarily translated into equity in improved outcomes for African Americans. Heart failure in African Americans is characterized by a higher prevalence, especially at younger ages; more-adverse course with more frequent hospitalizations; and higher mortality rates compared to the general population. Despite this distinct disease profile, African Americans are remarkably underrepresented in large heart failure trials. This paper reviews the unique course of heart failure in African Americans and discusses treatment in the context of clinical trial evidence. African Americans with heart failure may respond differently to some standard therapies compared to whites, but low levels of enrollment of AAs in large clinical trials preclude valid conclusions in certain cases. An important exception is the African American Heart Failure Trial (AHeFT), a well-designed, prospective, randomized, placebo-controlled, double-blind study, that added a combination of fixed-dose isosorbide dinitrate/hydralazine (ISDN/ HYD) to standard therapy and showed a 43% improvement in survival and a 33% reduction in first hospitalizations. Despite compelling evidence from AHeFT, post hoc secondary analyses, and recommendations from current practice guidelines, ISDN/HYD remains underutilized in African Americans with heart failure. In this paper, we put forth a call to action for racial equity in clinical research and treatment in African Americans with heart failure.

Racial Differences in Heart Failure Therapeutics

Heart failure in African Americans has a phenotype that is distinct from that in non-African Americans and that demonstrates increased importance of hypertensive etiologies. Trial data demonstrate that African Americans receive significant benefit from beta blockade. Despite differences in the heart failure phenotype, therapy of heart failure in African Americans remains largely the same as in white heart failure cohorts, with the notable exception of the added benefits provided by combination of hydralazine and isosorbide dinitrate (HYD-ISDN), now regarded as highly indicated therapy by both the Heart Failure Society of America and the American College of Cardiology/American Heart Association heart failure guideline committees. HYD-ISDN in fixed combination is the first cardiovascular drug approved for a single ethnic or racial subset--self-designated African Americans.

Treatment of Heart Failure in African Americans: A Consensus Statement

Treatment of Heart Failure in African Americans: A Consensus Statement

Treatment of Heart Failure in African Americans: Executive Summary

Treatment of Heart Failure in African Americans: Executive Summary

Quality of Care of and Outcomes for African Americans Hospitalized With Heart Failure: Findings From the OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure) Registry

We sought to examine the characteristics, quality of care, and clinical outcomes for a large cohort of African-American patients hospitalized with heart failure (HF) in centers participating in a quality improvement initiative. Heart failure in African Americans is characterized by variations in natural history, lesser response to evidence-based therapies, and disparate health care. We hypothesized that a performance improvement program will achieve similar adherence to quality measures in African Americans admitted with HF compared with non-African Americans. The OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure) registry-based performance-improvement program includes a pre-specified 10% subgroup with 60- to 90-day follow-up. Data on quality of care measures and outcomes were analyzed for 8,608 African-American patients compared with 38,501 non-African-American patients. African Americans were significantly younger and more likely to receive evidence-based medications but less likely to receive discharge instructions and smoking cessation counseling. In multivariable analyses, African-American race was an independent predictor of lower in-hospital mortality (odds ratio 0.71; 95% confidence interval 0.57 to 0.87; p < 0.001) but similar hospital length of stay. After multivariable adjustment, post-discharge outcomes were similar for American-American and non-African-American patients, but African-American race was associated with higher angiotensin-converting enzyme inhibitor prescription and left ventricular function assessment; no other HF quality indicators were influenced by race. In the context of a performance-improvement program, African Americans with HF received similar or better treatment with evidence-based medications, less discharge counseling, had better in-hospital survival, and similar adjusted risk of follow-up death/repeat hospital stay.

Hypovitaminosis D in African Americans Residing in Memphis, Tennessee With and Without Heart Failure

Factors contributing to heart failure (HF) in African Americans (AA) are under investigation. Reduced 25(OH)D confers increased cardiovascular risk, including HF. We monitored serum 25(OH)D, 1,25(OH)2D3, parathyroid hormone (PTH), and creatinine clearance in 102 AA residing in Memphis: 58 hospitalized with decompensated HF of >or=4 weeks in 34 (21 men; 53.3 +/- 1.8 years) or of 1 to 2 weeks in 24 (17 men; 49.6 +/- 2.4 years) and associated with a dilated cardiomyopathy and reduced ejection fraction (<35%); 19 outpatients with compensated HF (14 men; 52.6 +/- 2.7 years) with comparable ejection fraction; 16 outpatients (9 men; 55.4 +/- 2.9 years) with heart disease, but without HF; and 9 healthy volunteers (3 men; 35.8 +/- 3.5 years). Serum 25(OH)D <or=30 ng/mL was found in 96% and 90% with protracted or short-term decompensated HF, where it was of moderate to marked severity (<20 ng/mL) in 83% and 76%, respectively. In patients with either compensated or no HF, 25(OH)D <30 ng/mL was found in 95% and 100%, respectively, and in 30% of volunteers. Normal serum 1,25(OH)2D3 did not differ between patients. Serum PTH >65 pg/mL was found in all AA with decompensated HF of >or=4 weeks (132.4 +/- 12.0 pg/mL) and 67% with 1 to 2 weeks duration (82.3 +/- 7.9 pg/mL), but only 11% with compensated HF (45.8 +/- 6.1 pg/mL), 12% without HF (29.6 +/- 5.4 pg/mL), and none of the volunteers (31.1 +/- 3.9 pg/mL). Creatinine clearance did not differ between patient groups. Hypovitaminosis D is prevalent amongst AA residing in Memphis, with or without HF. Elevations in serum PTH in keeping with secondary hyperparathyroidism are only found in AA with decompensated HF, where hypovitaminosis D and other factors are contributory.

Role of Digitalis in the Contemporary Management of Systolic Heart Failure in African Americans

Introduction: The effects of digitalis in patients with systolic heart failure (SHF) have not been evaluated in the era of contemporary medical therapy including the use of beta blockers. In the African-American Heart Failure Trial (A-HeFT), the fixed-dose combination of isosorbide dinitrate/hydralazine (FDC I/H) decreased mortality and morbidity and improved patient reported functional status in self-identified black patients with SHF stabilized on contemporary heart failure (HF) therapy. Objective: We investigated the effect of digitalis in A-HeFT. Methods: A pre-specified Kaplan-Meier survival analysis was performed to determine the effect of FDC I/H compared to placebo with or without the use of digitalis (n = 1050). Analogous retrospective analyses within the FDC I/H and placebo groups were performed. Results: In A-HeFT, 62% of patients received digitalis at baseline. Patients receiving digitalis had lower systolic BP (125 vs. 128 mmHg), diastolic BP (76 vs. 78 mmHg), and qualifying LV ejection fraction (23.3 vs. 25.6%). Concomitant medications were comparable for either ACEI or ARB (93%) and beta blockers (87%). Digitalis users had significantly higher use of diuretics (94 vs. 89%) and spironolactone (45 vs. 29%). Compared to placebo, FDC I/H was associated with 53% improvement in survival (p < 0.01), and a 32% decrease in death or first HF hospitalization (p < 0.01) in patients treated with digitalis. There was a trend for an increase in all-cause mortality in patients receiving digitalis (Table) that was noted in the placebo group (HR = 1.65; 95% CI 0.91-2.76; p = 0.102) and not the FDC I/H group (HR = 1.02; 95% CI 0.50-2.10; p = 0.96). Digitalis use was associated with a significant increase in the risk of mortality or first heart failure hospitalization. Conclusions: FDC I/H improved outcomes in patients with HF independent of the use of digitalis. Within the limitations of sub-group analysis, our data indicate that the use of digitalis was not associated with beneficial effects on morbidity and mortality in black patients with SHF receiving contemporary therapy.Tabled 1Effect of Digitalis on Outcomes in All A-HeFT PatientsOutcomeHazard Ratio95% CIRisk Increasep ValueDeath1.380.88-2.1138%0.166Death or 1st HF Hospitalization1.381.06-1.7438%0.015 Open table in a new tab

Association of African American Race with Elevated Pulmonary Artery Diastolic Pressure: Data from the Heart and Soul Study

Whether increased severity of heart failure in African Americans is a result of differences in cardiac physiology is uncertain. The end-diastolic pulmonary regurgitation (EDPR) gradient is associated with abnormal cardiac physiology. We hypothesized that African American race is associated with an elevated EDPR gradient that may partially predispose African Americans to heart failure. The Heart and Soul Study prospectively assessed the EDPR gradient in 480 patients with coronary disease. We used multivariable linear regression to investigate the independent association of African American race with EDPR gradient. Compared with 393 non-African Americans, the 87 African Americans had similar indices of left ventricular systolic and diastolic function, left ventricular mass index, mitral regurgitation, peak tricuspid regurgitation gradient, and pulmonary velocity time integral. However, the EDPR gradient was significantly higher in African Americans (4.2 +/- 3.3 mm Hg) than in Caucasians (3.1 +/- 2.5 mm Hg) or other racial groups (3.5 +/- 2.7 mm Hg) (P = .008). In a multivariable model, African American race was a significant predictor of elevated EDPR gradient (beta coefficient 0.75, P = .03). African American race is independently associated with an elevated EDPR gradient in patients with coronary artery disease.

41: Current status of heart transplantation as therapy for advanced heart failure in African Americans

Purpose: While therapies to treat advanced congestive heart failure have significantly improved outcomes, little is known about the survival benefit accrued by African American patients (AA) who undergo orthotopic heart transplantation(OHTx). Therefore, we evaluated pre-transplant patient characteristics and post-transplant survival of AAs compared to other groups using registry data.

African American Heart Failure Trial: Role of Endothelial Dysfunction and Heart Failure in African Americans

Heart failure (HF) in African Americans may have differences in etiology and drug response. Compared with coronary disease in whites, HF in African Americans is marked by increased prevalence, earlier onset, increased risk for hospitalization and mortality, and increased prevalence of hypertension as the underlying cause of disease. There are apparent differences in pathophysiology and response to cardiac drugs. Endothelial dysfunction is potentially among the hallmarks of HF in this population, with diminished release of nitric oxygen (NO), increased inactivation of NO caused by increased oxidant stress, and impaired antioxidant defenses. Novel approaches to HF in African Americans include the use of isosorbide dinitrate combined with hydralazine in a fixed-dose formulation, which may affect endothelial dysfunction and the relative contribution of NO deficiency in this population. The African American Heart Failure Trial (A-HeFT) demonstrated improvement in morbidity and mortality, including a 39% reduction in hospitalization, improvement in quality of life or functional status, and a 43% reduction in mortality. When added to standard therapy, isosorbide dinitrate and hydralazine provide an evidence-based approach to diminishing morbidity and mortality in this high-risk population.

Increased prevalence of concentric left ventricular hypertrophy in African-Americans: will an epidemic of heart failure follow?

Left ventricular hypertrophy (LVH), used in this review to denote abnormally increased left ventricular (LV) mass, is an important cardiac trait because of its association with numerous adverse cardiovascular outcomes including myocardial infarction and heart failure. LV mass is typically assessed by noninvasive cardiac imaging (echocardiography or MRI); electrocardiography is an insensitive measure. There are two predominant types of hypertrophy: concentric, where LV wall thickness is increased relative to cavity dimensions, and eccentric, where LV wall thickness is not increased relative to cavity dimensions. Several large studies indicate that the prevalence of concentric LVH is higher in African-Americans versus whites. Although there are data to suggest that concentric LVH results in systolic heart failure in animal models, such data are lacking in humans. How concentric LVH affects the prevalence of systolic and diastolic heart failure in African-Americans needs further study. Given the large burden of LVH among African-Americans, such data are needed to estimate the expected burden and type of heart failure which will occur in the future in this population.

Race, Pharmacogenomics, and Marketing: Putting BiDil in Context

This article endeavors to place into context recent developments surrounding the United States Food and Drug Administration recent approval of BiDil® (isosorbide dinitrate/hydralazine hydrochloride) (NitroMed, Inc., Lexington, MA) as the first ever race-specific drug—in this case to treat heart failure in African Americans. It focuses in particular on both commercial incentives and statistical manipulation of medical data as framing the drive to bring BiDil to market as a race-specific drug. In current discourse about pharmacogenomics, targeting a racial audience is perceived as necessary because at this point the technology and resources do not exist to scan efficiently every individual's genetic profile. The article argues that medical researchers may say they are using race as a surrogate to target biology in drug development, but corporations are using biology as a surrogate to target race in drug marketing. Pharmacogenomics may hold great promise, but on our way to that Promised Land, it is imperative to review such short cuts with a critical eye.

Aldosterone Synthase Promoter Polymorphism Predicts Outcome in African Americans With Heart Failure: Results From the A-HeFT Trial

We sought to evaluate the effect of the aldosterone synthase promoter polymorphism on heart failure outcomes for subjects in the African American Heart Failure Trial (A-HeFT). Genetic heterogeneity modulates clinical outcomes in subjects with heart failure (HF); however, little data exist in African American populations. A common polymorphism exists in the promoter region of the aldosterone synthase gene (CYP11B2) at position -344 (T/C). The -344C allele, associated with higher aldosterone synthase activity, has been linked to hypertension; however, its impact on outcomes in HF is unknown. A total of 354 subjects from A-HeFT participated in the GRAHF (Genetic Risk Assessment of Heart Failure in African Americans) substudy and were genotyped for the aldosterone synthase polymorphism. Patients were followed prospectively, and event-free survival (freedom from death and HF hospitalization) compared by CYP11B2 genotype. Of the cohort, 218 patients were TT, 114 CT, and 22 patients were CC. Baseline etiology, blood pressure, and functional class were not significantly different among the 3 cohorts. The C allele was associated with significantly poorer HF hospitalization-free survival with the best survival among TT subjects, intermediate for heterozygotes, and the poorest for CC homozygotes (p = 0.018), and a higher rate of death (% death TT/TC/CC = 1.8/3.5/18.2, p = 0.001). The TT genotype, more prevalent in blacks, was associated with greater impact of fixed combination of isosorbide dinitrate and hydralazine on the primary composite end point (p = 0.01). The aldosterone synthase promoter -344C allele linked to higher aldosterone levels is associated with poorer event-free survival in blacks with HF. The role of aldosterone receptor antagonists in diminishing this apparent genetic risk remains to be explored.