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Background: Heart failure (HF) is characterized by perturbations in energy homeostasis and metabolism. The reversibility and prognostic value of circulating markers associated with these changes remain unclear.Objectives: This study sought to describe the metabolomic profiles of patients along the spectrum of systolic HF, determine their association with adverse outcomes in a clinical trial of HF, and evaluate whether identified metabolites change with treatment for end-stage systolic HF.Methods: To assess association of metabolites with clinical outcomes, we evaluated a population of 453 chronic systolic HF patients who had been randomized to exercise training versus usual care. To assess change in metabolites with mechanical circulatory support, 41 patients with end-stage HF who underwent left ventricular assist device (LVAD) placement were studied. Targeted, quantitative profiling of 60 metabolites using tandem flow injection mass spectrometry was performed on frozen plasma samples obtained prior to randomization, as well as prior to and ≥90 days post-placement in the LVAD group. Principal components analysis was used for data reduction.Results: Five principal components analysis-derived factors were significantly associated with peak Vo2 levels at baseline in fully adjusted models. Of these, factor 5 (composed of long-chain acylcarnitines) was associated with increased risk of all 3 pre-specified clinical trial outcomes: all-cause mortality/all-cause hospitalization, all cause-hospitalization, and cardiovascular death or cardiovascular hospitalization. Individual components of factor 5 were significantly higher in patients with end-stage HF prior to LVAD placement and decreased significantly post-implantation.Conclusions: In chronic HF patients, circulating long-chain acylcarnitine metabolite levels were independently associated with adverse clinical outcomes and decreased after long-term mechanical circulatory support. These metabolites may serve as potential targets for new diagnostics or therapeutic interventions. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437). [ABSTRACT FROM AUTHOR]

Background: Circulating high-density lipoprotein particle (HDL-P) subfractions impact atherogenesis, inflammation, and endothelial function, all of which are implicated in the pathobiology of heart failure (HF)., Objectives: The authors sought to identify key differences in plasma HDL-P subfractions between patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) to determine their prognostic utility., Methods: Patients with HFrEF (n = 782), HFpEF (n = 1,004), and no HF (n = 4,742) were identified in the CATHGEN (Catheterization Genetics) biorepository of sequential patients undergoing cardiac catheterization. Nuclear magnetic resonance-based lipoprotein profiling was performed on frozen fasting plasma obtained at catheterization. The authors used multivariable analysis of covariance to compare high-density lipoprotein particle (HDL-P) subfractions across groups, and Cox proportional hazards modeling to determine associations between HDL-P subfractions and time to death or major adverse cardiac events., Results: Mean HDL-P size was greater in HFrEF than HFpEF, both of which were greater than in no HF (all 2-way p < 0.0001). By contrast, concentrations of small HDL-P and total HDL-P were lesser in HFrEF than HFpEF, which were both lesser than no HF (all 2-way p ≤ 0.0002). In both HFrEF and HFpEF, total HDL-P and small HDL-P were inversely associated with time to adverse events. These findings persisted after adjustment for 14 clinical covariates (including high-density lipoprotein cholesterol content, coronary artery disease, and the inflammatory biomarker GlycA), and in sensitivity analyses featuring alternate left ventricular ejection fraction definitions, or stricter inclusion criteria with diastolic dysfunction or left ventricular end-diastolic pressure thresholds., Conclusions: In the largest analysis of HDL-P subfractions in HF to date, derangements in HDL-P subfractions were identified that were more severe in HFrEF than HFpEF and were independently associated with adverse outcomes. These data may help refine risk assessment and provide new insights into the complex interaction of HDL and HF pathophysiology., (Copyright © 2019. Published by Elsevier Inc.)

Background: Despite initial in-hospital treatment of acute heart failure (HF), some patients experience worsening HF (WHF). There are limited data about the outcomes and characteristics of patients who experience in-hospital WHF., Methods and Results: We assessed the characteristics and outcomes of patients with and without WHF in the ASCEND-HF trial. Worsening HF was defined as at least 1 symptom or sign of new, persistent, or WHF requiring additional intravenous inotropic/vasodilator or mechanical therapy during index hospitalization. We assessed the relationship between WHF and 30-day mortality, 30-day mortality or HF hospitalization, and 180-day mortality. We also assessed whether there was a differential association between early (days 1-3) vs late (day ≥4) WHF and outcomes. Of 7,141 patients with acute HF, 354 (5%) experienced WHF. Patients with WHF were more often male and had a history of atrial fibrillation or diabetes, lower blood pressure, and higher creatinine. After risk adjustment, WHF was associated with increased 30-day mortality (odds ratio 13.37, 95% CI 9.85-18.14), 30-day mortality or HF rehospitalization (odds ratio 6.78, 95% CI 5.25-8.76), and 180-day mortality (hazard ratio 3.90, 95% CI 3.14-4.86) (all P values < .0001). There was no evidence of a difference in outcomes between early and late WHF (all P values for comparison ≥ .2)., Conclusions: Worsening HF during index hospitalization was associated with worse 30- and 180-day outcomes. Worsening HF may represent an important patient-centered outcome in acute HF and a focus of future treatments., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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 fractions <40% 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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Hyponatremia is a well known predictor of short-term outcomes in heart failure (HF); however, its impact on long-term survival in HF patients with systolic dysfunction is not well established., Methods and Results: Using the Duke Databank for Cardiovascular Diseases, we identified 1,045 patients with HF and systolic dysfunction undergoing cardiac catheterization from January 2000 through December 2008. The effect of hyponatremia as independent predictor of all-cause death and cardiovascular death/rehospitalization was examined using a multivariable Cox proportional regression model. Hyponatremia was present in 107/1,045 patients (10.2%). Hyponatremic patients were older, more likely to be anemic, with higher heart rate and levels of blood urea nitrogen, lower blood pressure, and more severe HF. Using an unadjusted analysis, hyponatremia was associated with higher risk of all-cause death (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.44-2.49; P < .0001) and of cardiovascular death/rehospitalization (HR 1.40, 95% CI 1.11-1.77; P = .005) at 4.5 years. When entered into a multivariable Cox model, hyponatremia remained significant for all-cause death (HR 1.42, 95% CI 1.07-1.88) and for cardiovascular death/rehospitalization (HR 1.45, 95% CI 1.14-1.86)., Conclusions: Hyponatremia is relatively common in HF patients with LV dysfunction and is independently associated with increased risk of all-cause mortality and cardiovascular mortality/rehospitalization., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Recently, the Food and Drug Administration approved implantable left ventricular assist devices (LVAD) as destination therapy (DT) for end-stage heart failure patients who are ineligible for cardiac transplantation., Objective and Study Design: This is a case series that describes the early results with DT LVAD at Duke University Medical Center (DUMC). An additional objective is to provide general information to a broad group of caregivers on this LVAD therapy, which is a new and developing treatment option. DATA SOURCE/COLLECTION METHODS: Pretreatment clinical condition and outcomes data were collected retrospectively on this cohort of patients through chart review. Outcomes in our patients are compared to data from prior studies and established databases., Principal Findings: Since approval of this therapy two years ago, 18 patients have been treated with implantable LVAD as DT at DUMC. The primary reason for ineligibility for transplant was advanced age (median age was 66). Nearly all of the patients (89%) were confined to the hospital requiring continuous inotropic infusions or temporary mechanical support (e.g., intra-aortic balloon pump) prior to LVAD. The 30-day survival following LVAD implantation was 94.5%; one-year survival was 60%. Eighty-nine percent of patients were successfully discharged to independent living. Operative mortality is similar to that of other cardiac surgery procedures performed on patients with advanced heart failure, while duration of intensive care stay and hospitalization remain considerably longer. PRINCIPAL LIMITATIONS: The principal limitation of this review is the absence of a control group of patients with end-stage heart failure who received conventional therapies. For this reason, the DT LVAD outcomes are compared to prior studies and database results., Conclusion: Implantable LVAD therapy provides new hope for end-stage heart failure patients who do not qualify for cardiac transplantation.

C-reactive protein (CRP) levels were measured in a cohort of 96 outpatients with heart failure. Baseline angiotensin-converting enzyme inhibitor plus beta-blocker use were associated with lower levels of CRP; no relation was found between CRP levels and aspirin or statin use.

Since beginning cardiac transplantation in 1985, Duke University Medical Center has performed 485 de novo heart transplants in adult recipients. Our program has broadened the access of patients to transplantation through the aggressive use of ventricular assist devices as bridge to transplant in patients with acute heart failure and shock, as well as through the introduction of an alternate list program for suboptimal transplant candidates. Despite this broadening of the recipient pool, our long-term outcomes have remained good, with 5-year survival of 75% and 10-year survival of 51%. Continued advances in immunosuppression and treatment for cardiac allograft vasculopathy seem likely to continue to improve long-term outcomes from cardiac transplantation. Expanding indications for VAD support (such as destination therapy) and continued improvements in this technology seem certain to impact patient selection and therefore the results of transplantation in the future. Appropriate triage of patients with advanced heart failure among available therapies will be the cornerstone of optimizing outcomes in this critically ill patient population.