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There is a paucity of data regarding sex differences in the profiles and outcomes of ambulatory patients on left ventricular assist device (LVAD) support who present to the emergency department (ED).We performed a retrospective analysis of 57,200 LVAD-related ED patient encounters from the 2010 to 2018 Nationwide Emergency Department Sample. International Classification of Diseases Clinical Modification, Ninth Revision and Tenth Revision, codes identified patients aged 18 years or older with LVADs and associated primary and comorbidity diagnoses. Clinical characteristics and outcomes were stratified by sex and compared. Multivariable logistic regression was used to evaluate predictors of hospital admission and death. Female patient encounters comprised 27.2% of ED visits and occurred at younger ages and more frequently with obesity and depression (all P.01). There were no sex differences in presentation for device complication, stroke, infection, or heart failure (all P.05); however, female patient encounters were more often respiratory- and genitourinary or gynecological related (both P.01). After adjustment for age group, diabetes, depression, and hypertension, male patient encounters had a 38% increased odds of hospital admission (95% confidence interval 1.20-1.58), but there was no sex difference in the adjusted odds of death (odds ratio 1.11, 95% confidence interval 0.86-1.45).Patient encounters of females on LVAD support have significantly different comorbidities and outcomes compared with males. Further inquiry into these sex differences is imperative to improve long-term outcomes.

Clinical studies have suggested the prognostic value of galectin-3, a marker of fibrosis, in chronic heart failure. However, the specific role of galectin-3, compared with established biomarkers, remains uncertain.The Penn Heart Failure Study was an ambulatory heart failure cohort that included 1385 participants with reduced (1141), preserved (106), and recovered (138) left ventricular ejection fraction (LVEF). Cox regression models determined the association between galectin-3 and risk of all-cause mortality, cardiac transplantation, or placement of a ventricular assist device. Receiver operating characteristic curves compared the prognostic accuracy of galectin-3, high-sensitivity soluble Toll-like receptor 2 (ST2), troponin I, and B-type natriuretic peptide (BNP) at 1 and 5 years. Higher galectin-3 levels were associated with an increased risk of adverse events (adjusted hazard ratio of 1.96 for each doubling in galectin-3; P .001). This association was most pronounced among participants with preserved LVEF (adjusted hazard ratio 3.30; P .001). At 5 years, galectin-3 was the most accurate discriminator of risk among participants with preserved LVEF (area under the curve 0.782; P = .81 vs high-sensitivity ST2; P = .029 vs troponin I; P = .35 vs BNP). BNP was most accurate among participants with reduced and recovered LVEF (areas under the curves 0.716 and 0.728, respectively).Galectin-3 could have prognostic value for long-term events among patients with heart failure and preserved ejection fraction.

Background Identification of heart failure (HF) patients at risk for hospitalization may improve care and reduce costs. We evaluated 9 biomarkers as predictors of cardiac hospitalization in chronic HF. Methods and Results In a multicenter cohort of 1,512 chronic HF outpatients, we assessed the association between 9 biomarkers and cardiac hospitalization with the use of a recurrent events approach. Over a median follow-up of 4 years, 843 participants experienced ≥1 hospitalizations (total 2,178 hospitalizations). B-type natriuretic peptide (BNP) and troponin I (TnI) exhibited the strongest associations with risk of hospitalization (hazard ratio [HR] 3.8 [95% confidence interval (CI) 2.9-4.9] and HR 3.3 [95% CI 2.8-3.9]; 3rd vs 1st tertiles). Soluble Fms-like tyrosine kinase receptor 1 (sFlt-1) exhibited the next strongest association (HR 2.8 [95% CI 2.4–3.4]), followed by soluble Toll-like receptor 2 (HR 2.3 [95% CI 2.0–2.8]) and creatinine (HR 1.9 [95% CI 1.6–2.4]). Within ischemic/nonischemic subgroups, BNP and TnI remained most strongly associated. Except for creatinine, HRs for all biomarkers studied were smaller within the ischemic subgroup, suggesting greater importance of cardiorenal interactions in decompensation of ischemic HF. Conclusion Although BNP and TnI exhibited the strongest associations with hospitalization, etiology-dependent associations for the remaining biomarkers suggest etiology-specific mechanisms for HF exacerbation. sFlt-1 exhibited a strong association with cardiac hospitalization, highlighting its potential role as a biomarker of HF morbidity.

We conducted a meta-analysis of pharmacogenomic substudies of three randomized trials conducted in patients with decompensated heart failure (HF) which were led by National Heart Lung and Blood Institute (NHLBI)-funded HF Network to test the hypothesis that candidate genes modulate net fluid loss and weight change in patients with decompensated HF treated with a furosemide-based diuretic regimen. Although none of the genetic variants previously shown to modulate the effects of loop diuretics in healthy individuals were associated with net fluid loss after 72 hours of treatment, a set of rare variants in the APOL1 gene, which codes for apolipoprotein L1 (P= 0.0005 in the random effects model) was associated with this endpoint. Moreover, a common variant in the multidrug resistance protein-4 coding gene (ABCC4, rs17268282) was associated with weight loss with furosemide use (P = 0.0001). Our results suggest that both common and rare genetic variants modulate the response to a furosemide-based diuretic regimen in patients with decompensated HF.

We analyzed quantitative echocardiographic data from a large heart failure cohort receiving medical and cardiac resynchronization therapy (CRT) to determine baseline predictors of progressive left ventricular (LV) enlargement.Quantitative echocardiograms were obtained at baseline and after 6 months in 776 outpatients with chronic heart failure who participated in MIRACLE (Multicenter InSync Randomized Clinical Evaluation) and MIRACLE-ICD (Multicenter InSync ICD Randomized Clinical Evaluation). We used multivariable regression to determine clinical, therapeutic, and echocardiographic characteristics that predicted a subsequent change in left ventricular end-diastolic volume (LVEDV). Over 6 months, LVEDV increased in 308 (40%) and decreased in 468 (60%) patients. Baseline mitral regurgitation and levels of plasma brain natriuretic peptide (BNP) independently predicted LV enlargement, whereas CRT predicted a decrease in LVEDV (all P.01). In all models tested, male gender was an independent risk factor for progressive LV enlargement (P.0001).Men show more prominent LV dilation than women in chronic heart failure despite medical and device therapy. Rates of LV remodeling are influenced further by mitral regurgitation, plasma BNP, and CRT. Future studies should take these clinical factors into account when determining the influence of genetic factors and novel therapies on ventricular remodeling in chronic heart failure.

A Multimarker Panel Improves Risk Prediction in Chronic Heart Failure Bonnie Ky, Benjamin French, James C. Fang, Nancy K. Sweitzer, Wayne C. Levy, AlanH.B.Wu, LeeR.Goldberg,Mariell Jessup, ThomasP.Cappola; Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, PA; Cardiovascular Medicine, Case Western University, Cleveland, OH; Cardiovascular Medicine, University of Wisconsin, Madison, WI; Cardiovascular Medicine, University of Washington, Seattle, WA; Department of Laboratory Medicine, University of California at San Francisco, San Francisco, CA

In the setting of acute decompensated heart failure, worsening renal function (WRF) and improved renal function (IRF) have been associated with similar hemodynamic derangements and poor prognosis. Our aim was to further characterize IRF and its associated mortality risk.Consecutive patients with a discharge diagnosis of congestive heart failure at the Hospital of the University of Pennsylvania were reviewed. IRF was defined as a ≥20% improvement and WRF as a ≥20% deterioration in glomerular filtration rate. Overall, 903 patients met the eligibility criteria, with 31.4% experiencing IRF. Baseline venous congestion/right-side cardiac dysfunction was more common (P ≤ .04) and volume of diuresis (P = .003) was greater in patients with IRF. IRF was associated with a greater incidence of preadmission (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.6-6.7; P.0001) and postdischarge (OR 1.8, 95% CI 1.2-2.7; P = .006) WRF. IRF was associated with increased mortality (adjusted hazard ratio 1.3, 95% CI, 1.1-1.7; P = .011), a finding largely restricted to patients with postdischarge recurrence of renal dysfunction (P interaction = .038).IRF is associated with significantly worsened survival and may represent the resolution of venous congestion-induced preadmission WRF. Unlike WRF, the renal dysfunction in IRF patients occurs independently from the confounding effects of acute decongestion and may provide incremental information for the study of cardiorenal interactions.