Highlights • Binding of albumin to diuretics are key to delivery to the nephron, and low albumin levels diminish intravascular oncotic pressures necessary to maintain intravascular volume for ...effective diuresis. • Based on prospectively collected data from two acute heart failure clinical trials (DOSE-AHF and ROSE-AHF), this may not be the case in acute heart failure populations largely free of nephrotic syndrome or cirrhosis. • Our data from two well characterized cohorts of patients with acute heart failure suggest that serum albumin may not be a helpful tool to guide decongestion strategies or determine effectiveness of therapy.
Abstract Background Cardiac troponin (cTn) levels offer prognostic information for patients with heart failure. Highly sensitive assays detect levels of cTn much lower than the 99th percentile of ...standard cTn assays. We hypothesize that cardiac troponin levels measured by a high-sensitivity assay provide better prognostic value compared with cTn levels measured by a standard assay in patients with chronic heart failure. Methods We measured high-sensitivity cTnT (hs-cTnT) and standard cardiac troponin I (cTnI) levels, as well as amino-terminal pro B-type natriuretic peptide (NT-proBNP) in 504 sequential stable patients with a history of heart failure who underwent elective coronary angiography, without acute coronary syndrome, and with 5-year follow-up of all-cause mortality. Results The median hs-cTnT level was 21.2 (interquartile range 12.3-40.9) ng/L and 170 subjects died over 5 years. In a head-to-head overall comparison, hs-cTnT provided increased prognostic utility compared with cTnI (area under the curve AUC 66.1% and AUC 69.4%, respectively, P = .03; 9.0% integrated discrimination improvement, P < .001; and 13.6% event-specific reclassification, P < .001), and was independent of NT-proBNP and renal function. Even within the subset of patients where cTn levels by both assays were above the limit of quantification, higher hs-cTnT is associated with a 2-fold increase in 5-year mortality risk after adjusting for traditional risk factors (tertile 1 vs 3: hazard ratio 95% confidence interval 2.0 1.3-3.2; P = .0002). Conclusion Cardiac troponin can be detected by the high-sensitivity assay in more patients with chronic heart failure than the standard assay, and may yield independent and better prognostic accuracy for mortality prediction than standard assay.
Highlights • Early readmission after heart failure hospitalization was often due to cardiovascular comorbidity. • ACE/ARB use was associated with lesser risk for early readmission/death. • ...Hypokalemia, but not hyperkalemia, was associated with increased cardiovascular readmission/death. • Despite detailed physical examination data from a trial cohort, readmission prediction was limited.
Abstract Background Acute decompensated heart failure (ADHF) can be complicated by electrolyte abnormalities, but the major focus has been concentrated on the clinical significance of serum sodium ...levels. Objectives This study sought to determine the prognostic significance of serum chloride levels in relation to serum sodium levels in patients with ADHF. Methods We reviewed 1,318 consecutive patients with chronic heart failure admitted for ADHF to the Cleveland Clinic between July 2008 and December 2013. We also validated our findings in an independent ADHF cohort from the University of Pennsylvania (n = 876). Results Admission serum chloride levels during hospitalization for ADHF were independently and inversely associated with long-term mortality (hazard ratio HR per unit change: 0.94; 95% confidence interval CI: 0.92 to 0.95; p < 0.001). After multivariable risk adjustment, admission chloride levels remained independently associated with mortality (HR per unit change: 0.93; 95% CI: 0.90 to 0.97; p < 0.001) in contrast to admission sodium levels, which were no longer significant (p > 0.05). Results were similar in the validation cohort in unadjusted (HR per unit change for mortality risk within 1 year: 0.93; 95% CI: 0.91 to 0.95; p < 0.001) and multivariable risk-adjusted analysis (HR per unit change for mortality risk within 1 year: 0.95; 95% CI: 0.92 to 0.99; p = 0.01). Conclusions These observations in a contemporary advanced ADHF cohort suggest that serum chloride levels at admission are independently and inversely associated with mortality. The prognostic value of serum sodium in ADHF was diminished compared with chloride.
Abstract Background Over the years, several methods have been developed to reliably quantify functional capacity in patients with heart failure. Few studies have investigated the prognostic value of ...these assessment tools beyond cardiorenal prognostic biomarkers in stable patients with chronic heart failure. Methods and Results We administered the Duke Activity Status Index (DASI) questionnaire, a self-assessment tool comprising 12 questions for estimating functional capacity, to 1,700 stable nonacute coronary syndrome patients with history of heart failure who underwent elective diagnostic coronary angiography with 5-year follow-up of all-cause mortality. In a subset of patients (n = 800), B-type natriuretic peptide (BNP) was measured. In our study cohort, the median DASI score was 26.2 (interquartile range IQR 15.5–42.7). Low DASI score provided independent prediction of a 3.3-fold increase in 5-year mortality risk (quartile 1 vs quartile 4: hazard ratio HR 3.33, 95% confidence interval CI 2.57–4.36; P < .0001). After adjusting for traditional risk factors, BNP, and estimated glomerular filtration rate, low DASI score still conferred a 2.6-fold increase in mortality risk (HR 2.57, 95% CI 1.64–4.15; P < .0001). Conclusions A simple self-assessment tool of functional capacity provides independent and incremental prognostic value for mortality prediction in stable patients with chronic heart failure beyond cardiorenal biomarkers.
Abstract Lower serum chloride (Cl) levels are strongly associated with increased long-term mortality after admission for acute heart failure (AHF). However, the therapeutic implications of serum Cl ...levels during AHF are unknown. We sought to determine the short-term clinical response and post-discharge outcomes associated with serum Cl levels in AHF. Serum Cl was measured at randomization (N=358) and during hospitalization from patients with AHF in the in the Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE-AHF) trial. Outcomes included diuretic response and renal function at 72 hours and death and rehospitalization at 60 and 180-days. Baseline Cl tertiles were: 84-98 meq/L; 99-102 meq/L; and 103-117 meq/L. Baseline Cl level was associated with diuretic efficiency (P<.001), but not change in cystatin C (P=0.30) at 72 hours; and was associated with 60-day death (HR 0.86, P=0.029), 60-day death and rehospitalization (HR 0.90, P=0.01), and 180-day death (HR 0.91, P=0.049). These associations were attenuated with additional adjustment for loop diuretic dose (P>0.05). Chloride change correlated with weight change (rho 0.18, P=0.001), cystatin C change (rho -0.35, P<.001), and cumulative sodium excretion (rho -0.21, P<.001), but was not associated with any clinical outcomes (P>0.05 for all). In conclusion, serum Cl levels in AHF were inversely associated with loop diuretic response and were prognostic. However, changes in Cl levels were associated with parameters of decongestion, but not with clinical outcomes.
Abstract Objectives The aim of this study was to perform a meta-analysis of currently available data regarding the prognostic significance of soluble suppression of tumorigenecity–2 (sST2) ...concentration in acute heart failure (AHF). Background Concentration of sST2 may have prognostic value in AHF. A comprehensive assessment of all available studies regarding sST2 in AHF is lacking. Methods Three databases (MEDLINE, Cochrane Library, and Scopus) were searched. Inclusion criteria were follow-up studies, papers published in English, enrollment of patients with AHF, and availability of median hazard ratios for all-cause death and other outcome measures, when available. Results Ten studies were included, with a global population of 4,835 patients and a median follow-up duration of 13.5 months. The following global hazard ratios calculated for log2 (sST2) were admission sST2 and all-cause death, 2.46 (95% confidence interval CI: 1.80 to 3.37; p < 0.001); discharge sST2 and all-cause death, 2.06 (95% CI: 1.37 to 3.11; p < 0.001); admission sST2 and cardiovascular death, 2.29 (95% CI: 1.41 to 3.73; p < 0.001); discharge sST2 and cardiovascular death, 2.20 (95% CI: 1.48 to 3.25; p < 0.001); admission sST2 and heart failure (HF) hospitalization, 1.21 (95% CI: 0.96 to 1.52; p = 0.060); discharge sST2 and HF hospitalization, 1.54 (95% CI: 1.03 to 2.32; p = 0.007); admission sST2 and all-cause death or HF hospitalization, 1.74 (95% CI: 1.24 to 2.45; p < 0.001); and discharge sST2 and all-cause death or HF hospitalization, 1.63 (95% CI: 1.14 to 2.33; p < 0.001). Conclusions Plasma sST2 has prognostic value with respect to all-cause and cardiovascular death as well as the composite outcome of all-cause death or HF hospitalization, with both admission and discharge values having prognostic efficacy. Discharge sST2, but not admission sST2, is predictive of HF rehospitalization during follow-up.
Background Discordance between left- and right-sided filling pressures occurs in a subset of patients presenting with acute decompensated heart failure (ADHF). We hypothesized that a ...disproportionately increased right atrial pressure (RAP) relative to the pulmonary capillary wedge pressure (PCWP) would be associated with both renal dysfunction and mortality in ADHF. Methods A total of 367 patients admitted with ADHF with elevated intracardiac filling pressures were treated with intensive medical therapy guided by invasive hemodynamic monitoring. Baseline characteristics, hemodynamics, and renal function at admission were stratified by RAP/PCWP quartiles. The association of RAP/PCWP quartile with all-cause mortality after a median follow-up of 2.4 years was assessed in univariable and multivariable models, which included adjustment for the RAP. Results The median RAP/PCWP was 0.58 (interquartile range 0.43-0.75). Increasing RAP/PCWP was inversely associated with estimated glomerular filtration rate at baseline and with treatment ( P < .0001) independently of RAP. High RAP/PCWP was associated with increased mortality (quartile 4 vs 1: hazard ratio 95% CI 2.1 1.3-3.5, P = .002). The association of RAP/PCWP with mortality persisted after adjustment for age, gender, mean arterial pressure, RAP, cardiac index, pulmonary vascular resistance, and estimated glomerular filtration rate (hazard ratio 2.4 1.4-3.9, P = .007). Conclusion A disproportionate increase in right to left ventricular filling pressures is associated with renal dysfunction and mortality, independently of the right atrial pressure.
Abstract Background Worsening renal function in heart failure may be related to increased venous congestion, decreased cardiac output, or both. Diuretics are universally used in acute decompensated ...heart failure, but they may be ineffective and may lead to azotemia. We aimed to compare the decongestive properties of a urine output–guided diuretic adjustment and standard therapy for the management of cardiorenal syndrome in acute decompensated heart failure. Methods and Results Data were pooled from subjects randomized to the stepwise pharmacologic care algorithm (SPCA) in the CARRESS-HF trial and those who developed cardiorenal syndrome (rise in creatinine >0.3 mg/dL) in the DOSE-AHF and ROSE-AHF trials. Patients treated with SPCA (n = 94) were compared with patients treated with standard decongestive therapy (SDT) that included intravenous loop diuretic use (DOSE-AHF and ROSE-AHF; n = 107) at the time of cardiorenal syndrome and followed for net fluid balance, weight loss, and changing renal function. The SPCA group had higher degrees of jugular venous pressure ( P < .0001) at the time of cardiorenal syndrome. The group that received SPCA had more weight change (−3.4 ± 5.2 lb) and more net fluid loss (1.705 ± 1.417 L) after 24 hours than the SDT group (−0.8 ± 3.4 lb and 0.892 ± 1.395 L, respectively; P < .001 for both) with a slight improvement in renal function (creatinine change −0.1 ± 0.3 vs 0.0 ± 0.3 mg/dL, respectively; P = .03). Conclusions Compared with SDT, patients who received an intensification of medication therapy for treating persisting congestion had greater net fluid and weight loss without being associated with renal compromise.
Abstract Objectives This study evaluated the prevalence, profile, and prognosis of severe obesity in a large contemporary acute heart failure (AHF) population. Background Better prognosis has been ...reported for obese heart failure (HF) patients than nonobese HF patients, but in other cardiovascular populations, this effect has not been demonstrated for severely obese patients. Methods A cohort of 795 participants with body mass index (BMI) measured at time of admission and complete follow-up were identified from enrollment in 3 contemporary AHF trials (DOSE Diuretic Strategies Optimization Evaluation, CARRESS-HF Cardiorenal Rescue Study in Acute Decompensated Heart Failure, and ROSE Renal Optimization Strategies Evaluation in Acute Heart Failure). Patients were divided into 4 BMI categories according to standard World Health Organization criteria, as follows: normal weight: 18.5 to 25 kg/m2 n = 128; overweight: 25 to 29.9 kg/m2 n = 209; mild-to-moderate obese: 30 to 39.9 kg/m2 n = 301; and severely obese: ≥40 kg/m2 n = 157). The relationship between BMI and 60-day composite outcome (death, rehospitalization, or unscheduled provider visit) was investigated. Results Patients with severe obesity (19.7%) were younger, more often female, hypertensive, diabetic, and more likely to have higher blood pressures and left ventricular ejection fraction, and lower N-terminal pro-B-type natriuretic peptide and troponin I levels than other BMI category patients. Following admission for AHF, patients with normal weight showed the highest risk of 60-day composite outcome, followed by patients who were severely obese. Overweight and mild-moderately obese patients showed lowest risk. Conclusions Nearly one-fifth of AHF patients enrolled in contemporary randomized clinical trials are severely obese. A U-shaped curve for short-term prognosis according to BMI is seen in AHF. These findings may help to better inform both HF clinical care and future clinical trial planning.
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