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Although the number of successful pregnancies in heart transplantation (HT) recipients is increasing, data regarding outcomes after delivery are limited. The 2010 to 2015 Nationwide Inpatient Sample was queried to identify index hospitalizations for delivery in HT recipients. Adverse delivery events of HT patients were compared with those of women without history of HT or systolic heart failure (HF) undergoing delivery. Of 21,922,631 delivery hospitalizations, 94 hospitalizations were of HT recipients. Compared with women without a history of HF or HT, post-HT women had greater comorbidity burden, as evidenced by the Elixhauser Comorbidity Index (1.16 vs 0.24, p0.001), lower household incomes (p = 0.03), and were more likely to deliver at large hospitals (90% vs 58%, p = 0.02) and hospitals categorized as teaching institutions (100% vs 59%, p0.001). After adjustment for clinical variables, history of HT was significantly associated with increased incidence of hypertensive disorders of pregnancy (odds ratio 6.97, p = 0.001) primarily driven by increased rates of preeclampsia, and induction of labor (odds ratio 3.18, p = 0.01). There were no differences in gestational diabetes, cesarean section, fetal growth restriction, fetal malformations, or preterm delivery (all p0.3). In conclusion, post-HT women have greater comorbidity burden and experience increased maternal risks compared with women without history of HT or systolic HF, including increased risk of hypertensive disorders of pregnancy and need for induction. More studies are needed to improve obstetric care and maternal-fetal outcomes for the HT population.

There is no clear consensus on a lower cutoff value for normal left ventricular ejection fraction (EF) and the prognostic implications of low normal EF (LNEF) are poorly understood, particularly in Blacks. Therefore, we investigated the association of LNEF and incident heart failure (HF) in a community-based cohort of Blacks. We studied 3,669 participants (mean age 54 years, 63% women) of the Jackson Heart Study without prevalent HF or coronary heart disease (CHD). Participants were divided into three groups: (1) Reduced EF (

Hyperuricemia and gout are common in patients with heart failure (HF) and are associated with poor outcomes. Data describing hyperuricemia and gout in patients with HF with preserved ejection fraction (HFpEF) are limited. We used data from the Duke University Health System to describe characteristics of patients with HFpEF and hyperuricemia (serum uric acid >6 mg/dl) or gout (gout diagnosis or gout medication within the previous year) and to explore associations with 5-year outcomes (death and hospitalization). We identified 7,004 patients in the Duke University Health System with a known diagnosis of HFpEF who underwent transthoracic echocardiography between January 1, 2005 and December 31, 2017. A total of 1,136 (16.2%) patients with HFpEF also had hyperuricemia or gout. Patients with HFpEF and hyperuricemia or gout had a greater co-morbidity burden, more echocardiographic findings of cardiac remodeling, and higher unadjusted rates of all-cause death, all-cause hospitalization, and HF hospitalization compared with those with HFpEF without hyperuricemia or gout. After multivariable adjustment, patients with HFpEF and hyperuricemia or gout had a significantly higher rates of first all-cause hospitalization (adjusted hazard ratio 1.10 [95% confidence interval 1.02 to 1.19]; p = 0.020) and recurrent all-cause hospitalization (associated rate ratio 1.13 [95% confidence interval 1.01 to 1.25]; p = 0.026). After adjustment, no significant differences in death or HF hospitalization were observed. In conclusion, patients with HFpEF and hyperuricemia or gout were found to have a higher burden of co-morbidities and a higher rate of all-cause hospitalization, even after multivariable adjustment, compared to patients with HFpEF without hyperuricemia or gout.

Patients with chronic kidney disease (CKD) and/or end-stage renal disease are less active and experience significant functional limitations. The impact of a structured aerobic exercise intervention on outcomes in ambulatory heart failure (HF) patients with comorbid CKD is unknown. HF-ACTION enrolled 2,331 outpatients with HF and a reduced ejection fraction (i.e., ≤35%) from April 2003 to February 2007 and randomized them to aerobic exercise training versus usual care. Patients were grouped according to the presence of CKD, defined as an estimated glomerular filtration rate60 ml/min/1.73 m

A growing number of countries and geographical regions are involved in major clinical trials. Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure is the largest trial in acutely decompensated heart failure (HF) with patients from 5 geographical regions: North America (NA), Latin America (LA), Western Europe (WE), Central Europe (CE), and Asia-Pacific (AP). Data from the 5 geographical, areas were compared including baseline characteristics, medications, 30-day outcomes (mortality and mortality or HF hospitalization), and 180-day mortality. Of the 7,141 study patients, 3,243 (45.4%) were from NA (average of 15.2 patients/site), 1,762 (24.7%) from AP (28.4 patients/site), 967 (13.5%) from CE (20.2 patients/site), 665 (9.3%) from LA (17.1 patients/site), and 504 (7.1%) from WE (14.4 patients/site). There were marked differences in co-morbidities, clinical profile, medication use, length of stay, 30-day event rates, and 180-day mortality by region. Compared with NA, the adjusted risk for death or HF hospitalization at 30 days was significantly lower in CE (odds ratio [OR] 0.46, 95% CI 0.33 to 0.64), WE (OR 0.52 95% CI 0.35 to 0.75), and AP (OR 0.62 95% CI 0.48 to 0:79) and numerically lower in LA (OR 0.77, 95% CI 0.57 to 1.04) with similar results for 180-day mortality. In conclusion, in patients with acutely decompensated HF, major differences in baseline characteristics, treatments, length of the hospital stay, and 30-day HF rehospitalization rates, and 180-day mortality were found in patients enrolled from different, geographical areas. (C) 2016 Elsevier Inc. All rights reserved.

Serum osmolality may fluctuate with neurohormonal activation and in response to certain therapeutics in patients with heart failure (HF). The clinical relevance of osmolality in patients with HF has not been defined. In this post hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan trial, we analyzed serum osmolality measured at discharge in 3,744 patients hospitalized for HF and reduced ejection fraction (EF ≤40%). Median follow-up was 9.9 months. The association between discharge osmolality and all-cause mortality (ACM) and composite cardiovascular mortality or HF hospitalization was nonlinear; and thus, patients were divided into low (≤284), normal (285 to 300), and high (≥300 mOsm/kg) osmolality. Median serum osmolality at discharge was 297 (290 to 304) mOsm/kg. Patients in the low osmolality group (n = 454,12.1%) were more likely to be younger, men, have lower rates of hypertension, coronary artery disease, chronic kidney disease, diabetes, and have lower serum sodium, creatinine, systolic blood pressure, and EF (all p0.001). Low discharge osmolality was associated with higher ACM (low 29.3%; normal 23.6%; high 25.2%; p = 0.04) and the composite endpoint (low 45.6%; normal 39.3%; high 41.8%; p = 0.04). After risk adjustment, a 15 mOsm/kg decrease in osmolality was predictive of higher ACM (hazard ratio 1.61, 95% CI 1.19 to 2.17) and the composite endpoint (hazard ratio 1.37, 95% CI 1.06 to 1.75) in the low osmolality group. These associations were not seen in patients with normal or high osmolality. Interaction analyses for tolvaptan treatment were nonsignificant (p0.4). In conclusion, low discharge serum osmolality was independently predictive of worse postdischarge mortality and readmission. Further study is required to clarify the clinical utility of serum osmolality in hospitalized patients with HF.

Conflicting data exist regarding the associations of early repolarization (ER) with electrocardiogram (ECG) and clinical outcomes in blacks. We examined the association of ER defined by J point elevation (JPE) and all-cause mortality, and heart failure (HF) hospitalization in blacks in the Jackson Heart Study (JHS) cohort. We included JHS participants with ECGs from the baseline visit coding JPE and excluded participants with paced rhythms or QRS duration ≥120 ms. We compared the cumulative incidence of 10-year all-cause mortality and 8-year HF hospitalization by presence of JPE ≥0.1 mV in any ECG lead at baseline using Kaplan-Meier estimates and multivariable Cox models. Of the 4,978 participants, 1,410 (28%) had JPE at baseline: anterior leads 97.8%, lateral leads 8.3%, and inferior leads 2.9%. Compared with participants without JPE, those with JPE were younger, more likely to be male and current smokers, and less likely to have hypertension. Over a median follow-up of 8 years, there were no significant differences in the cumulative incidence or multivariable-adjusted hazards of all-cause mortality or HF hospitalization in participants with and without JPE in any lead (adjusted hazard ratio 0.97, 95% confidence interval 0.89 to 1.52, and adjusted hazard ratio 1.18, 95% confidence interval 0.9 to 1.54, respectively). Of the 2,523 participants who completed Exam 3 without JPE at baseline, 246 (10%) developed JPE over follow-up. In conclusion, JPE on ECG was not associated with long-term mortality or HF hospitalization in a large prospective black community cohort, suggesting that ER may represent a benign ECG finding in blacks.

Despite the well-established benefits of mineralocorticoid receptor agonists (MRAs) in heart failure with reduced ejection fraction, safety concerns remain in patients with concomitant diabetes mellitus (DM) because of common renal and electrolyte abnormalities in this population. We analyzed all-cause mortality and composite cardiovascular mortality and HF hospitalization over a median 9.9 months among 1,998 patients in the placebo arm of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial by DM status and discharge MRA use. Of the 750 patients with DM, 59.2% were receiving MRAs compared with 62.5% in the non-DM patients. DM patients not receiving MRAs were older, more likely to be men, with an ischemic heart failure etiology and slightly worse renal function compared with those receiving MRAs. After adjustment for baseline risk factors, among DM patients, MRA use was not associated with either mortality (hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.75 to 1.15) or the composite end point (HR 0.94; 95% CI 0.80 to 1.10). Similar findings were seen in non-DM patients (mortality [HR 1.01; 95% CI 0.84 to 1.22] or the composite end point [HR 0.98; 95% CI 0.85 to 1.13] [p >0.43 for DM interaction]). In conclusion, in-hospital initiation of MRA therapy was low (15% to 20%), and overall discharge MRA use was only 60% (with regional variation), regardless of DM status. There does not appear to be clear, clinically significant in-hospital hemodynamic or even renal differences between those on and off MRA. Discharge MRA use was not associated with postdischarge end points in patients hospitalized for worsening heart failure with reduced ejection fraction and co-morbid DM. DM does not appear to influence the effectiveness of MRA therapy.

In patients with heart failure (HF) with chronic obstructive pulmonary disease (COPD), concerns exist regarding β blockers, particularly noncardioselective β blockers, precipitating bronchospasm or attenuating the benefit of inhaled β(2) agonists. The aim of this study was to test the hypothesis that noncardioselective β blockers would not be associated with worse outcomes compared with cardioselective β blockers in patients with concomitant COPD in a large HF registry. A retrospective analysis of patients from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF) who had systolic dysfunction, documentation of β-blocker status, and follow-up information available after index hospitalization (n = 2,670) was performed. The associations between cardioselective and noncardioselective β blockers and the end points of 60- to 90-day mortality and mortality or rehospitalization in patients with (n = 722) and without (n = 1,948) COPD were analyzed using regression modeling. The models were adjusted for covariate predictors of β-blocker use at discharge and clinical predictors of outcomes. Noncardioselective and cardioselective β blockers were associated with lower risk-adjusted mortality in patients with and without COPD. There was no evidence that β-blocker selectivity was associated with a difference in outcomes between patients with and those without COPD (p for interaction >0.10 for both outcomes). In conclusion, despite concerns regarding β blockers in patients with HF with COPD, there was no evidence that β-blocker selectivity was associated with differences in outcomes for patients with HF with COPD versus those without.

Furosemide is the most commonly used loop diuretic in patients with heart failure (HF) despite data suggesting potential pharmacologic and antifibrotic benefits with torsemide. We investigated patients with HF in Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure who were discharged on either torsemide or furosemide. Using inverse probability weighting to account for the nonrandom selection of diuretic, we assessed the relation between choice of diuretic at discharge with 30-day mortality or HF hospitalization and 180-day mortality. Of 7,141 patients in the trial, 4,177 patients were included in this analysis, of which 87% (n = 3,620) received furosemide and 13% (n = 557) received torsemide. Torsemide-treated patients had lower ejection fraction and blood pressure and higher creatinine and natriuretic peptide level compared with furosemide. Torsemide was associated with similar outcomes on unadjusted analysis and nominally lower events on adjusted analysis (30-day mortality/HF hospitalization odds ratio 0.89, 95% CI 0.62 to 1.29, p = 0.55 and 180-day mortality hazard ratio 0.86, 95% CI 0.63 to 1.19, p = 0.37). In conclusion, these data are hypothesis generating and randomized comparative effectiveness trials are needed to investigate the optimal diuretic choice. (C) 2016 Elsevier Inc. All rights reserved.

We investigated the clinical profiles associated with serum uric acid (sUA) levels in a large cohort of patients hospitalized for worsening chronic heart failure with ejection fraction (EF) ≤40%, with specific focus on gender, race, and renal function based interactions. In 3,955 of 4,133 patients (96%) with baseline sUA data, clinical characteristics and outcomes were compared across sUA quartiles. The primary end points were all-cause mortality and a composite of cardiovascular mortality or heart failure hospitalization. Interaction analyses were performed for gender, race, and baseline renal function. Median follow-up was 9.9 months. Mean sUA was 9.1 ± 2.8 mg/dl and was higher in men than in women (9.3 ± 2.7 vs 8.7 ± 3.0 mg/dl, p0.001) and in blacks than in whites (10.0 ± 2.7 vs 9.0 ± 2.8 mg/dl, p0.001). Higher sUA was associated with lower systolic blood pressure and EF, higher natriuretic peptides, and more impaired renal function. After accounting for 24 baseline covariates, in patients with enrollment estimated glomerular filtration rate ≥30 ml/min/1.73 m(2), sUA was strongly associated with increased all-cause mortality (hazard ratio 1.44, 95% confidence interval 1.22 to 1.69, p0.001) and the composite end point (hazard ratio 1.44, 95% confidence interval 1.26 to 1.64, p0.001). However, in patients with estimated glomerular filtration rate30 ml/min/1.73 m(2), sUA was not related with either end point (both p0.4). Adjusted interaction analyses for gender, race, and admission allopurinol use were not significant. In conclusion, sUA is commonly elevated in patients hospitalized for worsening chronic heart failure and reduced EF, especially in men and blacks. The prognostic use of sUA differs by baseline renal function, suggesting different biologic and pathophysiologic significance of sUA among those with and without significant renal dysfunction.

Women have traditionally been underrepresented in heart failure (HF) trials, and their baseline characteristics and outcomes after hospitalization for HF are unclear. We retrospectively analyzed the clinical characteristics and outcomes of patients according to gender in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial. EVEREST randomized 4,133 patients hospitalized for HF and ejection fraction of ≤40% to tolvaptan or placebo, in addition to standard therapy. The median follow-up was 9.9 months. Log-rank tests and multivariate Cox regression models were used to compare the hazards of all-cause mortality and cardiovascular mortality or HF hospitalization. Women constituted 1,058 (26%) of the study population. The baseline characteristics were similar except that the women were older with more hypertension and diabetes and less chronic renal insufficiency, previous myocardial infarction, previous coronary revascularization, and baseline defibrillator implantation (all p0.001). The baseline use of evidence-based HF medical therapies was similar between genders (all p0.30). Despite a high event rate, no difference was seen in all-cause mortality (men 27% vs women 24%, multivariate hazard ratio 1.04, p = 0.61) or cardiovascular mortality plus HF hospitalization (men 42% vs women 39%, multivariate hazard ratio 1.11, p = 0.10) on univariate analysis or after adjusting for baseline covariates. In conclusion, women hospitalized for worsening HF with an ejection fraction of ≤40% were older, had more hypertension, and had received fewer procedure-based interventions than men but had relatively similar HF medication usage and clinical findings. After hospitalization for HF, women have a similarly high risk of long-term HF morbidity and mortality compared with men.

Myocardial ischemic origin is a significant independent predictor of mortality in patients with heart failure (HF). The implications of angina pectoris (AP) in HF are less well characterized. The aim of this study was to compare the clinical characteristics and outcomes of patients with and without AP in a cohort of patients with reduced ejection fractions and ischemic cardiomyopathy (iCM). Patients who underwent coronary angiography at Duke University Medical Center from January 2000 to September 2009 with ejection fractions40% and diagnoses of iCM with AP in the previous 6 weeks were compared to similar patients without AP. Time to event was examined using Kaplan-Meier methods for 5 end points: death; death or nonfatal myocardial infarction (MI); death, MI, or revascularization; death or hospitalization; and cardiovascular (CV) death or CV hospitalization. Of 2,376 patients with iCM, 1,412 (59%) had AP. They had more co-morbidities and more previous revascularization than patients without AP. After multivariate adjustment, those with and without AP had similar risks for death (p = 0.32), death or MI (p = 0.15), and death or hospitalization (p = 0.37) (5-year event rates 41% vs 41%, 46% vs 47%, and 87% vs 85%, respectively), but those with AP had lower rates of death, MI, or revascularization (p = 0.01) and higher rates of CV death or CV hospitalization (p = 0.03) (5-year event rates 85% vs 87% and 77% vs 73%, respectively). In conclusion, AP is common in patients with iCM despite medical therapy and previous revascularization and is associated with increased CV death or CV rehospitalization.