International Journal of Cardiology 177 (2014) 255–260

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Racial differences in mortality in patients with advanced systolic heart failure: Potential role of right ventricular ejection fraction Michel White a,⁎, Kanan Patel b, Guillem Caldentey a, Prakash Deedwania c, Raya Kheirbek d, Ross D. Fletcher d, Inmaculada B. Aban e, Alexander Lo e, Wilbert S. Aronow f, Gregg C. Fonarow g, Stefan D. Anker h, Ali Ahmed d a

Montreal Heart Institute, Université de Montréal, Montréal, Quebec, Canada University of California, San Francisco, CA, USA University of California, Fresno, San Francisco, CA, USA d Veterans Affairs Medical Center, Washington, DC, USA e University of Alabama at Birmingham, Birmingham, AL, USA f New York Medical College, Valhalla, NY, USA g Ahmanson-UCLA Cardiomyopathy Center, Los Angeles, CA, USA h Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany b c

a r t i c l e

i n f o

Article history: Received 24 March 2014 Received in revised form 16 September 2014 Accepted 20 September 2014 Available online 28 September 2014 Keywords: Race Heart failure Ejection fraction Mortality

a b s t r a c t In Beta-Blocker Evaluation of Survival Trial (BEST) bucindolol significantly reduced mortality among Caucasians with systolic heart failure (HF) but not among African Americans. Whether this differential effect can be explained by racial differences in baseline characteristics has not been previously examined. Of the 2708 BEST participants, 627 were African Americans. Because African Americans were more likely to be younger and women, we used age–sex-adjusted hazard ratios (HR) and 95% confidence intervals (CI) to estimate their outcomes (vs. Caucasians). A step-wise multivariable-adjusted model using 24 baseline characteristics was used to identify variables associated with between-race outcome differences and propensity-matching was used to determine independence of associations. Age–sex-adjusted HR for all-cause mortality for African Americans during 2 years of mean follow-up was 1.27. African Americans were more likely to have lower right ventricular ejection fraction. African Americans had no association with mortality among propensity-matched patients. The higher risk of death among African Americans in BEST may in part be due to their lower RVEF which may in part explain the lack of response to bucindolol among these patients. Future studies need to examine the role of low RVEF on the effect of beta-blockers in patients with systolic HF. © 2014 Elsevier Ireland Ltd. All rights reserved.

1. Introduction Population-based studies have suggested that African American patients with heart failure (HF) have a higher mortality rate than Caucasians with the same condition [1]. This finding has been attributed to differences in the severity, causes and management of HF, the prevalence of coexisting conditions and, also to socioeconomic factors [2,3]. Moreover, in equally treated patients it has been shown that racial differences may still exist [4]. Whether differences in the cardiac intrinsic or modulated functions or response to drug treatment contribute to these disparities has been incompletely assessed. In fact, African-

⁎ Corresponding author at: Université de Montreal, Montreal Heart Institute, 5000 Belanger Street, Montreal, Quebec H1T 1C8, Canada. Tel.: +1 514 376 3330; fax: +1 514 376 0173. E-mail address: [email protected] (M. White).

http://dx.doi.org/10.1016/j.ijcard.2014.09.094 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.

American patients with HF respond less to angiotensin modulating agents [5] while the use of a direct vasodilator treatment with the combination of hydralazine–nitrates has shown to be effective in these patients [6–8]. Although bucindolol had no overall mortality benefit in the BetaBlocker Evaluation of Survival Trial (BEST), in a subgroup analyses, Caucasian patients exhibited a significant survival benefit to treatment while African-American yielded no significant differences in mortality (P for interaction, 0.02) [9]. Whether these results could be related to chance or a decreased effectiveness of beta-blockers in African American patients remains unanswered [10]. Furthermore, whether if this racial difference in response to bucindolol therapy can be explained by racial differences in baseline characteristics has not been previously examined. In particular, the BEST was unique among beta-blocker trials in HF because data on right ventricular ejection function (RVEF) were collected. Therefore, the objective of present study is to determine the association between race and outcomes in the BEST, and examine if

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racial differences in various baseline characteristics, in particular, RVEF, may help explain a racial difference in outcomes. 2. Methods 2.1. Study design and patients The BEST was a multicenter randomized placebo-controlled clinical trial of bucindolol, a non-selective beta-blocker in patients with chronic advanced systolic HF [9]. The rationale, design and results of the BEST have been published in the past [11,12]. Briefly, 2708 HF patients with systolic dysfunction (left ventricular ejection fraction {LVEF}; b35%) and New York Heart Association (NYHA) class III–IV symptoms were randomized to receive bucindolol or placebo between May 31, 1995 and December 31, 1998 from 90 different sites across the United States and Canada. Over 90% of these patients were receiving angiotensin-converting enzyme (ACE) inhibitors, diuretics, and digitalis. For the purpose of the current study, we used a public-use copy of the BEST dataset, available with 2707 patients (one did not consent to be included in the de-identified public-use copy of the data) obtained from the National Heart, Lung, and Blood Institute (NHLBI), which also sponsored the BEST along with the Department of Veterans Affairs (VA). The trial was terminated early by study sponsors (NHLBI and VA) at the recommendation of the data and safety monitoring board after the 7th interim analysis due to the “totality of evidence regarding the usefulness of beta-blocker treatment derived from the BEST and other studies” and a report based on data collected through July 26, 1999 demonstrated that there was no significant mortality difference between the two treatment groups. All-cause mortality occurred in 33% (n = 449) of patients in the placebo group and 30% (411) of patients in the bucindolol group (hazard ratio (HR), 0.90; 95% confidence interval (CI), 0.78–1.02; P = 0.10). However, a subgroup analysis suggested that bucindolol significantly reduced the risk of total mortality among non-black patients (HR, 0.82; 95% CI, 0.70–0.96; P = 0.01) but not among African Americans (HR, 1.17; 95% CI, 0.89–1.53; P = 0.27; interaction P = 0.02). Because of smaller number of participants with other race, we excluded 185 Hispanic or other race participants. Thus, the final sample size for the current study was 2522 participants including 627 African-Americans and 1895 Caucasians. 2.2. Study outcomes The primary outcome of interest for current analysis was all-cause mortality. Secondary outcomes included cause-specific mortality and hospitalizations. All outcomes were centrally adjudicated. 2.3. Assembly of a balanced study cohort To reduce significant imbalances in baseline characteristics between patients with African American and Caucasians (Table 1), we used propensity score matching to assemble a balanced cohort. We estimated propensity scores for each of the 2522 patients using a non-parsimonious multivariable logistic regression model, in which African American was the dependent variable and other baseline characteristics displayed in Fig. 1 were used as covariates [13,14]. Then we used a greedy matching protocol to match 276 African Americans with another 276 Caucasians who had similar propensity scores [15–17]. Absolute standardized differences were estimated to assess the effectiveness of propensity score model and presented as a Love plot (Fig. 1) [18,19]. An absolute standardized difference of 0% would indicate no residual bias and values b10% are considered inconsequential. 2.4. Statistical analyses For baseline characteristics, Pearson's Chi-square and Wilcoxon rank-sum tests for pre-match, and McNemar's test and paired sample t-test for post-match comparisons, as appropriate (Table 1). Kaplan–Meier plots were used to determine the associations of African Americans with outcomes during mean follow-up of 2 years. We examined the association of race with outcomes among pre-match participants using bivariate and step-wise multivariable Cox regression hazard models. Because measure baseline characteristics are balanced in propensity-matched cohorts, we also used bivariate Cox proportional hazard models to determine the associations of race with outcomes among matched participants. A formal sensitivity analysis was conducted to estimate the degree of hidden bias that could potentially explain away a significant association among matched patients [20]. All statistical tests were two-tailed and P value b0.05 was considered as statistically significant. SPSS for Windows version 20 was used for data analysis.

3. Results Matched patients (n = 552) had a mean age of 56 years, and 25% were female. Baseline characteristics pre-match imbalances and postmatch balances are presented in Table 1 and Fig. 1. Before matching, African American HF patients were more likely to be younger, female and smoker and had higher prevalence of diabetes and hypertension. They also had lower LVEF (22% vs. 23% for Caucasians) and right

ventricular ejection fraction (RVEF; 32% vs. 36% for Caucasians). They were more likely to receive diuretic but less likely to receive statin. There were no differences in other key HF medications such as betablocker, ACE inhibitor, angiotensin receptor blockers or digitalis. After matching, we were able to achieve a balance cohort. 3.1. Outcomes All-cause mortality occurred in 33% of African American and 32% of Caucasian HF patients before matching (unadjusted hazard ratio {HR}, 1.10; 95% confidence interval {CI}, 0.94–1.29; P = 0.228; Table 2 and Fig. 2 left panel). After adjustment with age and sex, the association became significant (HR, 1.27; 95% CI, 1.08–1.50; P = 0.003; Table 2 right panel). Similar association was observed in full model after including LVEF with other covariates (HR, 1.20; 95% CI, 1.01–1.43; P = 0.043) but lost significantly when RVEF was added either into full model (HR, 1.17; 95% CI, 0.98–1.39; P = 0.089) or to the age–sex-adjusted model (HR, 1.15; 95% CI, 0.98–1.36; P = 0.093; Table 2). In matched cohort, all-cause mortality occurred in 33% and 36% of African American and Caucasian HF patients, respectively (HR, 0.86; 95% CI, 0.65–1.15; P = 0.316; Table 2). Pre- and post-match associations of African American race with other outcomes are displayed in Table 3. 4. Discussion Findings from the current study demonstrate that among patients with advanced systolic heart failure enrolled in the BEST, African Americans were younger and more likely to be women compared to Caucasians. These facts could explain the lack of differences in age– sex-adjusted mortality between the two races. African Americans had a significantly lower mean RVEF. When adjusted for the full model including 23 baseline characteristics but excluding RVEF the association remained significant. However, when adjusted for RVEF alone or RVEF added to the full model, the association lost its significance, suggesting that the lower RVEF among African Americans may also underlie the high mortality among these patients. These findings suggest that African American patients with advanced HF may be characterized by a low RVEF, which may explain their higher mortality, which in turn may modulate their response to beta-blocker therapy. The absence of mortality benefit of beta-blockers in African American patients showed in the BEST may be explained by differences in baseline characteristics, in particular a lower mean RVEF among African Americans. Racial difference in neurohormonal modulation as demonstrated by a relatively less response to renin– angiotensin–aldosterone blockade and lesser sympathetic nervous activation may also be associated with a decrease response to betaadrenergic blockade [21]. Another investigation has reported that black patients could have lesser beta-adrenoceptor sensitivity than Caucasians [22]. This study would be in agreement that despite some beneficial effect of chronic beta adrenergic blockade in both Caucasian and African-American populations [23], the efficacy of beta-blockers could be higher in Caucasian [24,25]. Other potential mechanisms include an increased oxidative stress which may be related to an increase rate of hypertension and diabetes in AfricanAmericans [26]. In addition, previous studies have shown a marked impairment in endothelial vasomotor function in black patients with hypertension [27], explaining the beneficial clinical effect of increasing the biodisponibility of nitric oxide in this population [28]. Differences in baseline characteristics between Caucasians and African-Americans in the BEST could also contribute to disparities in the results. In accordance to previous publications in the BEST [29,30], black population had more incidences of hypertension and diabetes. Also, black patients in that trial represented a population with major incidence of cardiovascular risk factors, with more signs of congestion and a greater need for diuretic treatment suggesting a less compensated state of HF in this population [3]. Nevertheless, the proportion of

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Table 1 Baseline characteristics of patients by race, before and after propensity score matching. Variables Mean (±SD) or n (%)

Before propensity score matching African American (n = 627)

After propensity score matching

Caucasian (n = 1895)

P value

African American (n = 276)

Caucasian (n = 276)

P value

Age (years) Female Current smoker Years of smoking

56 (±13) 180 (29%) 134 (21%) 19 (±17)

62 (±12) 367 (19%) 313 (17%) 22 (±18)

b0.001 b0.001 0.006 b0.001

58 (±13) 68 (25%) 58 (21%) 21 (±17)

58 (±12) 68 (25%) 64 (23%) 21 (±17)

0.447 1.000 0.621 0.924

Past medical history Coronary artery disease Acute myocardial infarction Diabetes Hypertension Hyperlipidemia Atrial fibrillation Chronic kidney disease Pacemaker Duration of heart failure

267 (43%) 158 (25%) 244 (39%) 488 (78%) 195 (31%) 112 (18%) 183 (29%) 38 (6%) 50 (±47)

1225 (65%) 680 (36%) 642 (34%) 1000 (53%) 906 (48%) 508 (27%) 766 (40%) 184 (10%) 49 (±49)

b0.001 b0.001 0.022 b0.001 b0.001 b0.001 b0.001 0.005 0.762

143 (52%) 88 (32%) 102 (37%) 191 (69%) 103 (37%) 65 (24%) 88 (32%) 17 (6%) 51 (±46)

143 (52%) 86 (31%) 97 (35%) 192 (70%) 91 (33%) 70 (25%) 89 (32%) 20 (7%) 50 (±51)

1.000 0.925 0.723 1.000 0.299 0.679 1.000 0.728 0.795

Medications Bucindolol ACE inhibitor Angiotensin receptor blockers Digitalis Diuretics Vasodilators Anti-arrhythmics Coumadin Aspirin Statins

322 (51%) 578 (92%) 34 (5%) 589 (94%) 613 (98%) 288 (46%) 10 (2%) 245 (39%) 264 (42%) 104 (17%)

945 (50%) 1733 (92%) 128 (7%) 1738 (92%) 1748 (92%) 835 (44%) 59 (3%) 849 (45%) 863 (46%) 460 (24%)

0.518 0.565 0.238 0.071 b0.001 0.414 0.043 0.012 0.134 b0.001

137 (50%) 251 (91%) 19 (7%) 260 (94%) 266 (96%) 133 (48%) 6 (2.2%) 110 (40%) 117 (42%) 58 (21%)

139 (50%) 257 (93%) 15 (5%) 258 (94%) 270 (98%) 133 (48%) 7 (2.5%) 118 (43%) 120 (44%) 49 (18%)

0.932 0.392 0.597 0.856 0.454 1.000 1.000 0.523 0.865 0.380

Clinical examination Body mass index (kg/m2) Heart rate (beats/min) Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) S3 gallop Jugular venous distension NYHA class IV

37 (±9) 85 (±14) 118 (±19) 75 (±12) 320 (51%) 314 (50%) 51 (8%)

37 (±8) 81 (±13) 117 (±18) 70 (±11) 767 (41%) 829 (44%) 156 (8%)

0.100 b0.001 0.040 b0.001 b0.001 0.006 0.938

37 (±9) 83 (±14) 118 (±19) 73 (±11) 131 (48%) 126 (46%) 25 (9%)

37 (±9) 84 (±13) 118 (±19) 73 (±12) 136 (49%) 137 (50%) 24 (9%)

0.785 0.445 0.858 0.882 0.745 0.371 1.000

X-ray/ECG/echocardiography finding Pulmonary edema Left bundle branch block Cardiothoracic ratio Left ventricular EF (%) Right ventricular EF (%)

95 (15%) 113 (18%) 58 (±7) 22 (±7) 32 (±11)

196 (10%) 530 (28%) 55 (±7) 23 (±7) 36 (±12)

0.001 b0.001 b0.001 0.005 b0.001

37 (13%) 59 (21%) 57 (±7) 23 (±7) 33 (±11)

37 (13%) 54 (20%) 57 (±7) 22 (±7) 33 (±12)

1.000 0.665 0.803 0.319 0.936

139.4 (±3) 4.2 (±0.50) 1.7 (±0.3) 133 (±80) 8.8 (±2.5) 152 (±106) 1.31 (±0.4) 0.8 (±0.5) 4.0 (±0.5) 193 (±49) 6.5 (±2.1) 13.5 (±1.7) 24 (±16) 28.6 (±17) 530 (±375)

138.8 (±3) 4.4 (±0.47) 1.8 (±0.2) 134 (±73) 7.9 (±2.3) 236 (±273) 1.23 (±0.4) 0.8 (±0.4) 4.1 (±0.4) 196 (±49) 7.8 (±2.1) 14.1 (±1.6) 25 (±15) 26.4 (±14) 516 (±286)

b0.001 b0.001 b0.001 0.774 b0.001 b0.001 b0.001 0.327 b0.001 0.273 b0.001 b0.001 0.166 0.002 0.349

Laboratory values Serum sodium (mEq/L) Serum potassium (mEq/L) Serum magnesium (mEq/L) Serum glucose (mg/dL) Serum uric acid (mg/dL) Serum triglycerides (mg/dL) Serum creatinine (mg/dL) Serum bilirubin (mg/dL) Serum albumin (g/dL) Total cholesterol (mg/dL) White blood cell count (103/μL) Hemoglobin b (g/dL) Blood urea nitrogen (mg/dL) Aspartate aminotransferase (U/L) Plasma norepinephrine

139.2 (±3) 4.3 (±0.5) 1.7 (±0.3) 136 (±78) 8.4 (±2.4) 173 (±129) 1.29 (±0.4) 0.8 (±0.5) 4.0 (±0.5) 194 (±49) 7.2 (±2.3) 13.8 (±1.6) 24 (±16) 27.5 (±17) 536 (±405)

139.1 (±3) 4.3 (±0.4) 1.7 (±0.2) 135 (±71) 8.4 (±2.4) 171 (±101) 1.26 (±0.5) 0.8 (±0.4) 4.1 (±0.4) 192 (±47) 7.2 (±1.6) 13.8 (±1.7) 23 (±14) 28.0 (±21) 521 (±270)

0.691 0.791 0.908 0.918 0.802 0.805 0.539 0.587 0.278 0.711 0.794 0.835 0.647 0.760 0.599

ACE inhibitors = angiotensin-converting enzyme inhibitors, NYHA = New York Heart Association, ECG = electrocardiography, EF = ejection fraction.

patients treated with ACE inhibitors and beta-blockers was similar among groups. Supposedly, nitrates and hydralazine were not part of the conventional HF treatment as A-HEFT trial was published after the BEST publication. In multivariate analyses of the primary end-point for different variables, African-American showed worse outcomes, and only the addition of RVEF in the analyses neutralized these observations. Accordingly, black patients had a higher incidence of HF hospitalization before propensity match scoring. Nevertheless when analyzing data with propensity score matching and comparing with a similar population, these differences were no longer significant.

The reasons for a lower RVEF in black patients in the BEST remain speculative. Before propensity matching, black patients exhibited a lower prevalence of coronary artery disease and a higher prevalence of hypertension. These two conditions suggest that cardiac involvement may have been more diffuse explaining a higher rate of RV failure in black patients. We may also speculate that black patients may present with some difference in intrinsic and modulated responses to adaptation following cardiac injury. These hypotheses need to be validated and investigated in other trials.

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Bucindolol ACE inhibitors Angiotensin receptor blockers Digitalis Diuretics Vasodilators Anti-arrhythmics Coumadin Aspirin Statins Serum sodium Serum potassium Serum chloride Serum bicarbonate Serum magnesium Serum phosphorus Serum glucose Serum cholesterol Serum triglyceride Serum protein Serum creatinine Serum calcium Serum bilirubin Serum albumin Uric acid Hematocrit White blood cell count Hemoglobin b Platelet count Blood urea nitrogen Alkaline phosphatase Aspartate aminotransferase Alanine aminotransferase Plasma norepinephrine Partial thromboplastine time International normalized ratio

Age, years Female Current smoker Years of smoking Body mass index Coronary artery disease Angina pectoris Diabetes mellitus Hypertension Hyperlipidemia Atrial fibrillation Ventricular fibrillation Peripheral vascular disease Thromboembolic disease Chronic kidney disease Valvular replacement Pacemaker Ablation Implanted cardio defibrillator Duration of heart failure Heart rate Systolic blood pressure Diastolic blood pressure Pulmonary rales Peripheral edema S3 gallop S4 gallop Jugular venous distention Hepatomegaly NYHA class IV Pulmonary edema Left bundle branch block Right bundle branch block Cardiothoracic ratio Left ventricular ejection fraction Right ventricular ejection fraction

Absolute standardized difference (%) Fig. 1. Love plots displaying absolute standardized differences comparing baseline characteristics between African American and white, before and after propensity score matching (ACE inhibitors = angiotensin-converting enzyme inhibitors; NYHA = New York Heart Association).

4.1. Limitations The main limitation of the present study is its retrospective character and the absence of randomization. However, studies of racial differences are often observational in nature. The reason for why black patients had a major incidence of unknown cause of mortality remains unanswered, although this is unlikely to confound the overall association with total mortality due to the low number of events for deaths due to unknown causes. To better evaluate the effect of race in outcomes it should be of interest to further investigate some other larger contemporary studies

where a larger number of black subjects have been enrolled. In addition, prospective study may help addressing some clinical and mechanistic issues related to race and HF. 4.2. Conclusions Findings from the current study demonstrate that in the BEST, compared to Caucasians, African Americans with advanced systolic HF were younger and more likely to be women, and when adjusted for age and sex, they had higher risk of death, which was in part explained by

Table 2 Association of all-cause mortality by race in BEST trial. All-cause mortality

Pre-match (n = 2522) Model 1: unadjusted Model 2: model 1 + age, sex Model 3: model 2 + medical historyb Model 4: model 3 + medicationsc Model 5: model 4 + clinical examinations/lab valuesd Model 6: model 5 + RVEFe Model 7: age + sex + RVEFe Post-match (n = 552) Propensity-matched a

% (events) African American

Caucasian

n = 627 33% (208) – – – – – – n = 276 33% (90)

n = 1895 32% (598) – – – – – – n = 276 36% (99)

Absolute risk differencea

Hazard ratio (95% CI)

P value

+1% – – – – – –

1.10 (0.94–1.29) 1.27 (1.08–1.50) 1.35 (1.14–1.60) 1.29 (1.09–1.53) 1.20 (1.01–1.43) 1.17 (0.98–1.39) 1.15 (0.98–1.36)

0.228 0.003 0.001 0.003 0.043 0.089 0.093

–3%

0.86 (0.65–1.15)

0.316

Absolute risk difference was calculated by subtracting the percentage of events in the Caucasian group from that in the African American group. Medical history: smoking years, duration of heart failure, NYHA class, acute myocardial infarction, diabetes mellitus, hypertension, atrial fibrillation, ventricular fibrillation, peripheral vascular disease, chronic kidney disease. c Medications: bucindolol, ACE inhibitor, angiotensin-receptor blockers, digitalis, diuretics. d Clinical examinations/lab values: body mass index, heart rate, systolic blood pressure, diastolic blood pressure, serum sodium, serum potassium, serum albumin, left ventricular ejection fraction. e RVEF = right ventricular ejection fraction. b

M. White et al. / International Journal of Cardiology 177 (2014) 255–260

African American White HR=1.10; 95% CI=0.94–1.29; p=0.228

Before propensity score matching; Age-sex-adjusted All-cause mortality

All-cause mortality

Before propensity score matching

259

African American

Follow-up (years)

White HR=1.27; 95% CI=1.08–1.50; p=0.003

Follow-up (years)

Fig. 2. Kaplan–Meier plots for all-cause mortality by race before propensity score matching (HR = hazard ratio; CI = confidence interval).

Table 3 Association of race on outcomes before and after propensity score matching. Outcome, % of events (number of events)

Pre-match

Post-match

African American (n = 627)

Caucasian (n = 1895)

HR (95% CI) P-value

African American (n = 276)

Caucasian (n = 276)

HR (95% CI) P-value

27% (169)

27% (514)

26% (73)

31% (85)

9% (57)

10% (190)

7% (20)

9% (25)

Sudden

15% (95)

14% (265)

16% (45)

16% (43)

Acute myocardial infarction

0.3% (2)

0.8% (16)

1.04 (0.88–1.24) P = 0.652 0.95 (0.71–1.28) P = 0.748 1.13 (0.90–1.43) P = 0.302 0.40 (0.09–1.72) P = 0.216 1.11 (0.62–2.00) P = 0.725 1.00 (0.61–1.63) P = 0.995 3.36 (1.73–6.53) P b 0.001 1.08 (0.96–1.21); P = 0.203 1.32 (1.15–1.52) P b 0.001 1.05 (0.90–1.23) P = 0.539

1% (2)

1% (4)

2% (6)

5% (13)

4% (12)

4% (12)

2% (5)

1% (2)

65% (179)

63% (175)

44% (122)

41% (113)

33% (92)

37% (103)

0.82 (0.60–1.12) P = 0.203 0.75 (0.42–1.36) P = 0.347 1.00 (0.66–1.52) P = 0.999 0.51 (0.09–2.77) P = 0.433 0.43 (0.16–1.12) P = 0.085 0.96 (0.43–2.14) P = 0.924 2.30 (0.45–11.89) P = 0.320 1.03 (0.84–1.27) P = 0.791 1.10 (0.85–1.42) P = 0.486 0.84 (0.64–1.12) P = 0.237

Cardiovascular mortality Heart failure

Others

2% (15)

2% (43)

Non-cardiovascular mortality

3% (21)

4% (67)

Unknown cause mortality

3% (18)

0.9% (17)

All-cause hospitalization

63% (395)

63% (1188)

Heart failure hospitalization

44% (273)

37% (696)

Death or transplant

34% (213)

34% (639)

their lower RVEF. Future studies need to examine the role of RVEF on outcomes among African American patients with HF and low LVEF, and its effect on beta-blocker therapy among these patients. 5. Funding sources Dr. Ahmed was supported by the National Institutes of Health through grants (R01-HL085561, R01-HL085561-S and R01-HL097047) from the National Heart, Lung, and Blood Institute and a generous gift from Ms. Jean B. Morris of Birmingham, Alabama. Dr. White holds the Carolyn and Richard Renaud Research Chair in Heart Failure of the Montreal Heart Institute. Conflict of interest There exists no conflict of interest. Acknowledgments All authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology and that they have read and approved the submission of the manuscript.

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Racial differences in mortality in patients with advanced systolic heart failure: potential role of right ventricular ejection fraction.

In Beta-Blocker Evaluation of Survival Trial (BEST) bucindolol significantly reduced mortality among Caucasians with systolic heart failure (HF) but n...
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