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Aims: Prior cohorts demonstrating the importance of serum chloride levels in heart failure either excluded or had partial representation of patients with heart failure with preserved ejection fraction (HFpEF). We aimed to examine the relationship between serum chloride concentration and outcomes in HFpEF.Methods and Results: We included participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) who met the following criteria: met inclusion by the natriuretic peptide stratum, had recorded serum chloride levels, and were from the Americas (n = 942). Multivariable Cox proportional hazards models tested the association of serum chloride with clinical outcomes, and mixed effects modelling tested the association of spironolactone or loop diuretic on serial serum chloride levels. The median serum chloride level was 102 [25th-75th percentile 100-105 mmol/L (range 84-114 mmol/L)]. After multivariable adjustment, every standard deviation decrease in serum chloride (4.05 mmol/L) was associated with ∼50% increased risk for cardiovascular death [hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.11-2.06, P = 0.008] and ∼30% increased risk for all-cause death (HR 1.29, 95% CI 1.02-1.62, P = 0.04), but not with the primary composite endpoint or heart failure hospitalization (P > 0.3 for both). There were no significant interactions between spironolactone use and the serum chloride-risk relationship (P > 0.1) for each endpoint. Spironolactone was not (P = 0.33) but loop diuretic use was associated with lower serial serum chloride levels (P < 0.001).Conclusion: Lower serum chloride was independently associated with increased risk of cardiovascular and all-cause death in HFpEF. Loop diuretic use, but not spironolactone, lead to a decrease in serum chloride levels over time. [ABSTRACT FROM AUTHOR]

Background: Serum chloride is an important homeostatic biomarker in left heart failure, with significant prognostic implications. The impact of serum chloride in the long-term survival of patients with pulmonary arterial hypertension (PAH) is unknown. We tested whether serum chloride levels are associated with long-term survival in patients with PAH.Methods: We included patients with idiopathic or heritable PAH who had a basic metabolic panel performed at the time of their diagnostic right heart catheterization. Laboratory results were recorded both at diagnosis and 6-month follow-up.Results: We included 277 patients, mean age 51 ± 18 years and 73% women, of whom 254 had a follow-up electrolyte determination at 6 months. Serum chloride was 102.9 ± 3.9 mM/L at diagnosis. A serum chloride ≤ 100 mM/L was noted in 65 (24%) and 53 (21%) patients at diagnosis and 6 months, respectively. Patients with serum chloride ≤ 100 mM/L at 6 months tracked with increase mortality when adjusted by age, sex, pulmonary vascular resistance, diuretics or prostacyclin analogs usage, and serum creatinine and sodium at 6 months (hazard ratio, 1.83; 95% CI, 1.11-3.00). This group of patients was older, with decreased functional capacity, had worse renal function, took more diuretics, had higher pulmonary artery wedge pressure but lower mean pulmonary artery pressure, transpulmonary gradient, and pulmonary vascular resistance.Conclusions: Serum chloride at 6 months from the PAH diagnosis is a strong and independent predictor of mortality in patients with idiopathic or heritable PAH, even after adjusting serum sodium, renal function, diuretic, and prostacyclin analog usage. [ABSTRACT FROM AUTHOR]

The gut microbiome recently has emerged as a novel risk factor that impacts health and disease. Our gut microbiota can function as an endocrine organ through its unique ability to metabolize various dietary precursors, and can fuel the systemic inflammation observed in chronic disease. This is especially important in the setting of chronic kidney disease, in which microbial metabolism can contribute directly to accumulation of circulating toxins that then can alter and shift the balance of microbiota composition and downstream functions. To study this process, advances in -omics technologies are providing opportunities to understand not only the taxonomy, but also the functional diversity of our microbiome. We also reliably can quantify en masse a wide range of uremic byproducts of microbial metabolism. Herein, we examine the bidirectional relationship between the gut microbiome and the failing kidneys. We describe potential approaches targeting gut microbiota for cardiovascular risk reduction in chronic kidney disease using an illustrative example of a novel gut-generated metabolite, trimethylamine N-oxide. [ABSTRACT FROM AUTHOR]

Aims: Hyponatraemia is strongly associated with adverse outcomes in heart failure. However, accumulating evidence suggests that chloride may play an important role in renal salt sensing and regulation of neurohormonal and sodium-conserving pathways. Our objective was to determine the prognostic importance of hypochloraemia in patients with heart failure.Methods and Results: Patients in the BEST trial with baseline serum chloride values were evaluated (n = 2699). Hypochloraemia was defined as a serum chloride ≤96 mmol/L and hyponatraemia as serum sodium ≤135 mmol/L. Hypochloraemia was present in 13.0% and hyponatraemia in 13.7% of the population. Chloride and sodium were only modestly correlated (r = 0.53), resulting in only 48.7% of hypochloraemic patients having concurrent hyponatraemia. Both hyponatraemia and hypochloraemia identified a population with greater disease severity; however, renal function tended to be worse and loop diuretic doses higher with hypochloraemia. In univariate analysis, lower serum sodium or serum chloride as continuous parameters were each strongly associated with mortality (P < 0.001). However, when both parameters were included in the same model, serum chloride remained strongly associated with mortality [hazard ratio (HR) 1.3 per standard deviation decrease, 95% confidence interval (CI) 1.18-1.42, P < 0.001], whereas sodium was not (HR 0.97 per standard deviation decrease, 95% CI 0.89-1.06, P = 0.52).Conclusion: Serum chloride is strongly and independently associated with worsened survival in patients with chronic heart failure and accounted for the majority of the risk otherwise attributable to hyponatraemia. Given the critical role of chloride in a number of regulatory pathways central to heart failure pathophysiology, additional research is warranted in this area. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to assess the haemodynamic response and tolerance to aggressive oral hydralazine/isosorbide dinitrate (HYD/ISDN) up-titration after intravenous vasodilator therapy in advanced decompensated heart failure (ADHF).Methods and Results: Medical records of 147 consecutive ADHF patients who underwent placement of a pulmonary artery catheter and received intravenous vasodilator therapy were reviewed. Intravenous sodium nitroprusside and sodium nitroglycerin as first-line agent for those with preserved blood pressures were utilized in 143 and 32 patients, respectively. Sixty-one percent of patients were converted to oral HYD/ISDN combination therapy through a standardized conversion protocol. These patients had a significantly higher admission mean pulmonary arterial wedge pressure compared with patients not converted (28 ± 7 vs. 25 ± 8 mmHg, respectively; P-value 0.024). Beneficial haemodynamic response to decongestive therapy, defined as low cardiac filling pressures and cardiac index ≥2.20 L/min/m(2) without emergent hypotension, was achieved in 32% and 29% of patients who did or did not receive oral HYD/ISDN, respectively (P-value 0.762). HYD/ISDN dosing was progressively and consistently decreased up to the moment of hospital discharge and during outpatient follow-up, primarily due to incident hypotension.Conclusion: The use of a standardized haemodynamically guided up-titration protocol for conversion from intravenous to oral vasodilators may warrant subsequent dose reductions upon stabilization. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is increasingly prevalent in patients with chronic systolic heart failure. Therefore, evidence-based therapies are more and more being used in patients with some degree of renal dysfunction. However, most pivotal randomized clinical trials specifically excluded patients with (severe) renal dysfunction. The benefit of these evidence-based therapies in this high-risk patient group is largely unknown. This paper reviews data from randomized clinical trials in systolic heart failure and the interactions between baseline renal dysfunction and the effect of randomized treatment. It highlights that most evidence-based therapies show consistent outcome benefit in patients with moderate renal insufficiency (stage 3 CKD), whereas there are very scarce data on patients with severe (stage 4 to 5 CKD) renal insufficiency. If any, the outcome benefit might be even greater in stage 3 CKD compared with those with relatively preserved renal function. However, prescription of therapies should be individualized with consideration of possible harm and benefit, especially in those with stage 4 to 5 CKD where limited data are available. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to explore the relationship between myeloperoxidase (MPO) and cardiac structure, performance, and prognosis. Background: Myeloperoxidase is an inflammatory marker that is elevated in patients with heart failure (HF) and cardiac dysfunction, with mechanistic links to plaque vulnerability and left ventricular (LV) remodeling. Methods: We evaluated plasma MPO levels (CardioMPO, PrognostiX, Inc., Cleveland, Ohio) in 140 patients with chronic systolic HF (LV ejection fraction <35%) and examined the plasma MPO levels’ relationships with echocardiographic indexes of systolic and diastolic performance, as well as long-term clinical outcomes (death, cardiac transplantation, or HF hospitalization). Results: Within the overall cohort, increasing plasma MPO levels were associated with increasing likelihood of more advanced HF (restrictive diastolic stage, right ventricular systolic dysfunction ≥3+, and tricuspid regurgitation area ≥1.8 cm2). Plasma MPO levels were predictive of long-term clinical outcomes (risk ratio [95% confidence interval] = 3.35 [1.52 to 8.86]), even after adjustment for age, LV ejection fraction, plasma B-type natriuretic peptide (BNP), creatinine clearance, or diastolic stage. In receiver-operator characteristic curve analyses, addition of MPO to BNP testing augmented the predictive accuracy of future adverse clinical events (area under the curve 0.66 for BNP only [chi-square test = 12.9, p = 0.0003], and 0.70 for BNP plus MPO [chi-square test = 15.87, p = 0.0004]). Conclusions: In chronic systolic HF, elevated plasma MPO levels are associated with an increased likelihood of more advanced HF. Moreover, elevated plasma MPO levels within a HF subject seem to be predictive of increased adverse clinical outcomes. [Copyright &y& Elsevier]

Background: The utility of N-terminal pro-BNP (NT-proBNP) measurement as a prognostic marker during nonurgent percutaneous coronary intervention (PCI) has been suggested in several studies. The comparative prognostic values between NT-proBNP levels and left ventricular ejection fraction (LVEF) in the nonurgent PCI setting are unclear. Methods: CREDO was a double blind, placebo-controlled, randomized trial comparing 2 clopidogrel regimens before and after nonurgent PCI. Baseline NT-proBNP levels and LVEF were measured in 1468 subjects using the Roche Elecsys proBNP assay (Roche Diagnostics, Indianapolis, IN), and the 1-year combined end point of death/myocardial infarction (MI)/stroke was analyzed according to NT-proBNP quartiles in impaired and preserved LVEF. Results: In this patient cohort (mean age 61.6 ± 10 years, 22% with LVEF <50%), the median NT-proBNP level was 131 pg/mL. Increasing quartiles of NT-proBNP were associated with a higher rate of death, MI, and the combined end point (but not stroke) at 1 year, including those with LVEF ≥50% (P < .001 for trend). This prognostic power for death and MI remained robust even when adjusted for other clinical or biochemical markers including cardiac troponin, creatinine clearance, and high-sensitive C-reactive protein (hazard ratio 1.249, P = .006). Despite its robust prognostic value, baseline NT-proBNP levels did not identify patients with enhanced benefit from pre-procedural and prolonged clopidogrel therapy. Conclusions: In patients undergoing a nonurgent PCI, NT-proBNP levels may provide important prognostic value for death and MI, even in patients with preserved cardiac function, However, NT-proBNP levels were unable to identify patients with enhanced benefit from pre-procedural and prolonged clopidogrel therapy. [Copyright &y& Elsevier]

Background: Worsening renal function (WRF) in the setting of aggressive diuresis for acute heart failure treatment may reflect renal tubular injury or simply indicate a hemodynamic or functional change in glomerular filtration. Well-validated tubular injury biomarkers, N-acetyl-β-d-glucosaminidase, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1, are now available that can quantify the degree of renal tubular injury. The ROSE-AHF trial (Renal Optimization Strategies Evaluation-Acute Heart Failure) provides an experimental platform for the study of mechanisms of WRF during aggressive diuresis for acute heart failure because the ROSE-AHF protocol dictated high-dose loop diuretic therapy in all patients. We sought to determine whether tubular injury biomarkers are associated with WRF in the setting of aggressive diuresis and its association with prognosis.Methods: Patients in the multicenter ROSE-AHF trial with baseline and 72-hour urine tubular injury biomarkers were analyzed (n=283). WRF was defined as a ≥20% decrease in glomerular filtration rate estimated with cystatin C.Results: Consistent with protocol-driven aggressive dosing of loop diuretics, participants received a median 560 mg IV furosemide equivalents (interquartile range, 300-815 mg), which induced a urine output of 8425 mL (interquartile range, 6341-10 528 mL) over the 72-hour intervention period. Levels of N-acetyl-β-d-glucosaminidase and kidney injury molecule 1 did not change with aggressive diuresis (both P>0.59), whereas levels of neutrophil gelatinase-associated lipocalin decreased slightly (-8.7 ng/mg; interquartile range, -169 to 35 ng/mg; P<0.001). WRF occurred in 21.2% of the population and was not associated with an increase in any marker of renal tubular injury: neutrophil gelatinase-associated lipocalin (P=0.21), N-acetyl-β-d-glucosaminidase (P=0.46), or kidney injury molecule 1 (P=0.22). Increases in neutrophil gelatinase-associated lipocalin, N-acetyl-β-d-glucosaminidase, and kidney injury molecule 1 were paradoxically associated with improved survival (adjusted hazard ratio, 0.80 per 10 percentile increase; 95% confidence interval, 0.69-0.91; P=0.001).Conclusions: Kidney tubular injury does not appear to have an association with WRF in the context of aggressive diuresis of patients with acute heart failure. These findings reinforce the notion that the small to moderate deteriorations in renal function commonly encountered with aggressive diuresis are dissimilar from traditional causes of acute kidney injury. [ABSTRACT FROM AUTHOR]

Background: Oxidative/nitrosative stress and endothelial dysfunction are hypothesized to be central to cancer therapeutics-related cardiac dysfunction (CTRCD). However, the relationship between circulating arginine-nitric oxide (NO) metabolites and CTRCD remains unstudied.Objectives: This study sought to examine the relationship between arginine-NO metabolites and CTRCD in a prospective cohort of 170 breast cancer patients treated with doxorubicin with or without trastuzumab.Methods: Plasma levels of arginine, citrulline, ornithine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and N-monomethylarginine (MMA) were quantified at baseline, 1 month, and 2 months after doxorubicin initiation. Determinants of baseline biomarker levels were identified using multivariable linear regression, and Cox regression defined the association between baseline levels and 1- or 2-month biomarker changes and CTRCD rate in 139 participants with quantitated echocardiograms at all time points.Results: Age, hypertension, body mass index, and African-American race were independently associated with ≥1 of baseline citrulline, ADMA, SDMA, and MMA levels. Decreases in arginine and citrulline and increases in ADMA were observed at 1 and 2 months (all p < 0.05). Overall, 32 participants experienced CTRCD over a maximum follow-up of 5.4 years. Hazard ratios for ADMA and MMA at 2 months were 3.33 (95% confidence interval [CI]: 1.12 to 9.96) and 2.70 (95% CI: 1.35 to 5.41), respectively, and 0.78 (95% CI: 0.64 to 0.97) for arginine at 1 month.Conclusions: In breast cancer patients undergoing doxorubicin therapy, early alterations in arginine-NO metabolite levels occurred, and early biomarker changes were associated with a greater CTRCD rate. Our findings highlight the potential mechanistic and translational relevance of this pathway to CTRCD. [ABSTRACT FROM AUTHOR]

More than 1 million heart failure hospitalizations occur annually, and congestion is the predominant cause. Rehospitalizations for recurrent congestion portend poor outcomes independently of age and renal function. Persistent congestion trumps serum creatinine increases in predicting adverse heart failure outcomes. No decongestive pharmacological therapy has reduced these harmful consequences. Simplified ultrafiltration devices permit fluid removal in lower-acuity hospital settings, but with conflicting results regarding safety and efficacy. Ultrafiltration performed at fixed rates after onset of therapy-induced increased serum creatinine was not superior to standard care and resulted in more complications. In contrast, compared with diuretic agents, some data suggest that adjustment of ultrafiltration rates to patients' vital signs and renal function may be associated with more effective decongestion and fewer heart failure events. Essential aspects of ultrafiltration remain poorly defined. Further research is urgently needed, given the burden of congestion and data suggesting sustained benefits of early and adjustable ultrafiltration. [ABSTRACT FROM AUTHOR]

Objective: The objective was to study whether the temporal pattern of transient hyponatremia development in acute heart failure might provide insight into its pathophysiology and prognostic relevance.Methods: A post hoc analysis of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) and Diuretic Optimization Strategies Evaluation in Acute Heart Failure (DOSE AHF) studies was performed (n = 716). Patients were stratified according to the temporal pattern of hyponatremia development: (1) no hyponatremia, (2) persistent hyponatremia, (3) decompensation hyponatremia disappearing with decongestive treatment, and (4) treatment-induced hyponatremia.Results: Transient decompensation versus no hyponatremia was associated with significantly elevated blood urea nitrogen/creatinine ratio (P < .001), plasma renin activity (P < .001), and plasma aldosterone levels (P < .001) at baseline. Disease severity characteristics of such patients were intermediate between no and persistent hyponatremia. In contrast, patients with treatment-induced versus no hyponatremia had similar baseline characteristics and comparable natriuretic peptide levels, and both groups had little neurohumoral activation at baseline. Diuretic efficacy, defined as net fluid balance (milliliters) per 40 mg furosemide-equivalent dose administered, was lower in patients with persistent or treatment-induced hyponatremia versus decompensation hyponatremia or no hyponatremia, respectively. The former versus latter groups also had more pronounced neurohumoral activation with decongestive treatment. The risk for all-cause mortality (hazard ratio, 2.50; 95% confidence interval, 1.50-4.19; P < .001) and death or heart failure readmission (hazard ratio, 2.18; 95% confidence interval, 1.60-2.97; P < .001) was significantly elevated in patients with persistent versus no hyponatremia, with the risk of decompensation and treatment hyponatremia situated in between.Conclusions: Transient hyponatremia is prognostically relevant, but it has a heterogeneous cause according to its temporal pattern of development. [ABSTRACT FROM AUTHOR]

Data supporting the use of oral isosorbide dinitrate and/or hydralazine (I/H) as add-on therapy to standard neurohormonal antagonists in advanced decompensated heart failure (ADHF) are limited, especially in the non–African-American population. Our objective was to determine if addition of I/H to standard neurohormonal blockade in patients discharged from the hospital with ADHF is associated with improved hemodynamic profiles and improved clinical outcomes. We reviewed consecutive patients with ADHF admitted from 2003 to 2006 with a cardiac index ≤2.2 L/min/m2 admitted for intensive medical therapy. Patients discharged with angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers (control group) were compared with those receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers plus I/H (I/H group). The control (n = 97) and I/H (n = 142) groups had similar demographic characteristics, baseline blood pressure, and renal function. Patients in the I/H group had a significantly higher estimated systemic vascular resistance (1,660 vs 1,452 dynes/cm5, p <0.001) and a lower cardiac index (1.7 vs 1.9 L/min/m2, p <0.001) on admission. The I/H group achieved a similar decrease in intracardiac filling pressures and discharge blood pressures as controls, but had greater improvement in cardiac index and systemic vascular resistance. Use of I/H was associated with a lower rate of all-cause mortality (34% vs 41%, odds ratio 0.65, 95% confidence interval 0.43 to 0.99, p = 0.04) and all-cause mortality/heart failure rehospitalization (70% vs 85%, odds ratio 0.72, 95% confidence interval 0.54 to 0.97, p = 0.03), irrespective of race. In conclusion, the addition of I/H to neurohormonal blockade is associated with a more favorable hemodynamic profile and long-term clinical outcomes in patients discharged with low-output ADHF regardless of race. [Copyright &y& Elsevier]

Objectives: Our aim was to determine the feasibility and value of a protocol-driven approach to patients with cardiac resynchronization therapy (CRT) who did not exhibit a positive response long after implant. Background: Up to one-third of patients with advanced heart failure do not exhibit a positive response to CRT. Methods: A total of 75 consecutive ambulatory patients with persistent advanced heart failure symptoms and/or adverse reverse remodeling and CRT implanted >6 months underwent a comprehensive protocol-driven evaluation to determine the potential reasons for a suboptimal response. Recommendations were made to maximize the potential of CRT, and adverse events were documented. Results: All patients (mean left ventricular [LV] ejection fraction 23 ± 9%, LV end-diastolic volume 275 ± 127 ml) underwent evaluation. Eighty-eight percent of patients had significantly better echocardiographic indexes of LV filling and LV ejection with optimal setting of their CRT compared with a temporary VVI back-up setting. Most patients had identifiable reasons for suboptimal response, including inadequate device settings (47%), suboptimal medical treatment (32%), arrhythmias (32%), inappropriate lead position (21%), or lack of baseline dyssynchrony (9%). Multidisciplinary recommendations led to changes in device settings and/or other therapy modifications in 74% of patients and were associated with fewer adverse events (13% vs. 50%, odds ratio: 0.2 [95% confidence interval: 0.07 to 0.56], p = 0.002) compared with those in which no recommendation could be made. Conclusions: Routine protocol-driven approach to evaluate ambulatory CRT patients who did not exhibit a positive response is feasible, and changes in device settings and/or other therapies after multidisciplinary evaluation may be associated with fewer adverse events. [Copyright &y& Elsevier]

Objectives: To determine whether venous congestion, rather than impairment of cardiac output, is primarily associated with the development of worsening renal function (WRF) in patients with advanced decompensated heart failure (ADHF). Background: Reduced cardiac output is traditionally believed to be the main determinant of WRF in patients with ADHF. Methods: A total of 145 consecutive patients admitted with ADHF treated with intensive medical therapy guided by pulmonary artery catheter were studied. We defined WRF as an increase of serum creatinine ≥0.3 mg/dl during hospitalization. Results: In the study cohort (age 57 ± 14 years, cardiac index 1.9 ± 0.6 l/min/m2, left ventricular ejection fraction 20 ± 8%, serum creatinine 1.7 ± 0.9 mg/dl), 58 patients (40%) developed WRF. Patients who developed WRF had a greater central venous pressure (CVP) on admission (18 ± 7 mm Hg vs. 12 ± 6 mm Hg, p < 0.001) and after intensive medical therapy (11 ± 8 mm Hg vs. 8 ± 5 mm Hg, p = 0.04). The development of WRF occurred less frequently in patients who achieved a CVP <8 mm Hg (p = 0.01). Furthermore, the ability of CVP to stratify risk for development of WRF was apparent across the spectrum of systemic blood pressure, pulmonary capillary wedge pressure, cardiac index, and estimated glomerular filtration rates. Conclusions: Venous congestion is the most important hemodynamic factor driving WRF in decompensated patients with advanced heart failure. [Copyright &y& Elsevier]

Objectives: This study was designed to examine the safety and efficacy of sodium nitroprusside (SNP) for patients with acute decompensated heart failure (ADHF) and low-output states. Background: Inotropic therapy has been predominantly used in the management of patients with ADHF presenting with low cardiac output. Methods: We reviewed all consecutive patients with ADHF admitted between 2000 and 2005 with a cardiac index ≤2 l/min/m2 for intensive medical therapy including vasoactive drugs. Administration of SNP was chosen by the attending clinician, nonrandomized, and titrated to a target mean arterial pressure of 65 to 70 mm Hg. Results: Compared with control patients (n = 97), cases treated with SNP (n = 78) had significantly higher mean central venous pressure (15 vs. 13 mm Hg; p = 0.001), pulmonary capillary wedge pressure (29 vs. 24 mm Hg; p = 0.001), but similar demographics, medications, and renal function at baseline. Use of SNP was not associated with higher rates of inotropic support or worsening renal function during hospitalization. Patients treated with SNP achieved greater improvement in hemodynamic measurements during hospitalization, had higher rates of oral vasodilator prescription at discharge, and had lower rates of all-cause mortality (29% vs. 44%; odds ratio: 0.48; p = 0.005; 95% confidence interval: 0.29 to 0.80) without increase in rehospitalization rates (58% vs. 56%; p = NS). Conclusions: In patients with advanced, low-output heart failure, vasodilator therapy used in conjunction with optimal current medical therapy during hospitalization might be associated with favorable long-term clinical outcomes irrespective of inotropic support or renal dysfunction and remains an excellent therapeutic choice in hospitalized ADHF patients. [Copyright &y& Elsevier]