Abstract Background Treatment of acute decompensated heart failure (ADHF) with loop diuretics, such as furosemide, is frequently complicated by insufficient urine sodium excretion. We hypothesize ...that insufficient natriuretic response to diuretic therapy, characterized by lower urine sodium (UNa ) and urine furosemide, is associated with subsequent inadequate decongestion, worsening renal function, and adverse long term events. Methods and Results We enrolled 52 consecutive patients with ADHF and measured serum and urine sodium (UNa ), urine creatinine (UCr ), and urine furosemide (UFurosemide ) levels on a spot sample taken after treatment with continuous intravenous furosemide, and followed clinical and renal variables as well as adverse long-term clinical outcomes (death, rehospitalizations, and cardiac transplantation). We observed similar correlations between UNa :UFurosemide ratio and UNa and fractional excretion of sodium (FENa ) with 24-hour net urine output ( r = 0.52–0.64, all P < .01) and 24-hour weight loss ( r = 0.44–0.56; all P < .01). Interestingly, FENa (but not UNa or UNa :UFurosemide ) were influenced by estimated glomerular filtration rate (eGFR). We observed an association between lower UNa :UFurosemide with greater likelihood of worsening renal function (hazard ratio HR 3.01; P = .02) and poorer adverse clinical outcomes (HR 1.63, P = .008) after adjusting for age and eGFR. Meanwhile, both diminished weight loss and net fluid output over 24 hours of continuous intravenous furosemide were observed when UNa :UFurosemide ratios were <2 mmol/mg or when UNa <50 mmol. Conclusion In patients with ADHF receiving continuous furosemide infusion, impaired natriuretic response to furosemide is associated with greater likelihood of worsening renal function and future adverse long-term outcomes, independently from and incrementally with decreasing intrinsic glomerular filtration.
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.
Abstract Background The development of worsening renal function (WRF, defined as creatinine rise ≥0.3 mg/dL) occurs frequently in the setting of acute decompensated heart failure (ADHF) and strongly ...predicts adverse clinical outcomes. Neutrophil gelatinase–associated lipocalin (NGAL) is produced by the nephron in response to tubular epithelial damage and serves as an early marker for acute renal tubular injury. We sought to determine the relationship between admission serum NGAL levels and WRF in the setting of ADHF. Methods and Results We measured serum NGAL levels in 91 patients admitted to the hospital with ADHF. Patients were adjudicated by independent physician into those that did or did not develop WRF over the ensuing 5 days of in-hospital treatment. In our study cohort (68% male, mean age 61 ± 15 years, mean left ventricular ejection fraction 31 ± 14%), median admission serum NGAL level was 165 ng/mL (interquartile range IQR 108–235 ng/mL). Thirty-five patients (38%) developed WRF within the 5-day follow-up. Patients who developed WRF versus those without WRF had significantly higher median admission serum NGAL levels (194 IQR 150–292 ng/mL vs. 128 IQR 97–214 ng/mL, P = .001). High serum NGAL levels at admission were associated with greater likelihood of developing WRF (odds ratio: 1.92, 95% confidence interval 1.23–3.12, P = .004). In particular, admission NGAL ≥140 ng/mL had a 7.4-fold increase in risk of developing WRF, with a sensitivity and specificity of 86% and 54%, respectively. Conclusions The presence of elevated admission serum NGAL levels is associated with heightened risk of subsequent development of WRF in patients admitted with ADHF.
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.
Objectives The goals of this study were to determine: 1) if low-risk patients assessed by a CHADS2 score, a clinical scoring system quantifying a risk of stroke in patients with atrial fibrillation ...(AF), require a routine screening transesophageal echocardiogram (TEE) before pulmonary vein isolation (PVI); and 2) the relationship of a CHADS2 score with left atrial (LA)/left atrial appendage (LAA) spontaneous echo contrast, sludge, and thrombus. Background There is no clear consensus of whether a screening TEE before catheter ablation of AF should be performed in every patient. Methods Initial TEEs for pre-PVI of 1,058 AF patients (age 57 ± 11 years, 80% men) were reviewed and compared with a CHADS2 score. Results CHADS2 scores of 0, 1, 2, 3, 4, 5, and 6 were present in 47%, 33%, 14%, 5%, 1%, 0.3%, and 0% of patients, respectively. The prevalence of LA/LAA thrombus, sludge, and spontaneous echo contrast were present in 0.6%, 1.5%, and 35%. The prevalence of LA/LAA thrombus/sludge increased with ascending CHADS2 score (scores 0 0%, 1 2%, 2 5%, 3 9%, and 4 to 6 11%, p < 0.01). No patient with a CHADS2 score of 0 had LA/LAA sludge/thrombus. In a multivariate model, history of congestive heart failure and left ventricular ejection fraction <35% were significantly associated with sludge/thrombus. Conclusions The prevalence of LA/LAA sludge/thrombus in patients with AF undergoing a pre-PVI screening TEE is very low (<2%) and increases significantly with higher CHADS2 scores. This suggests that a screening TEE before PVI should be performed in patients with a CHADS2 score of ≥1, and in patients with a CHADS2 score of 0 when the AF is persistent and therapeutic anticoagulation has not been maintained for 4 weeks before the procedure.
Objectives We hypothesized that an integrated assessment of arginine with its catabolic products might better predict cardiovascular risks than arginine levels alone. Background Arginine is the sole ...nitrogen source for nitric oxide (NO) synthesis. The major catabolic products of arginine are ornithine and citrulline. Methods Plasma levels of free arginine, ornithine, citrulline, and the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) were measured with liquid chromatography coupled with tandem mass spectrometry. We examined the relationship of global arginine bioavailability ratio (GABR) (defined as arginine/ornithine + citrulline) versus arginine and its catabolic metabolites to prevalence of significantly obstructive coronary artery disease (CAD) and incidence of major adverse cardiovascular events (MACE) (death, myocardial infarction, stroke) over a 3-year follow-up in 1,010 subjects undergoing elective cardiac catheterization. Results Patients with significantly obstructive CAD had significantly lower GABR (median interquartile range: 1.06 0.75 to 1.31 vs. 1.27 0.96 to 1.73, p < 0.001) and arginine levels mean: 68 ± 20 μmol/l vs. 74 ± 24 μmol/l, p < 0.001) than those without significantly obstructive CAD. After adjusting for Framingham risk score, C-reactive protein, and renal function, lower GABR (but not arginine levels) and higher citrulline levels remained significantly associated with both the prevalence of significantly obstructive CAD (adjusted odds ratio: 3.93, p < 0.001, and 5.98, p < 0.001, respectively) and 3-year risk for the incidence of MACE (adjusted hazard ratio: 1.98, p = 0.025, and 2.40, p = 0.01, respectively) and remained significant after adjusting for ADMA. Conclusions GABR might serve as a more comprehensive concept of reduced NO synthetic capacity compared with systemic arginine levels. Diminished GABR and high citrulline levels are associated with both development of significantly obstructive atherosclerotic CAD and heightened long-term risk for MACE.
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.
Indications for hospitalization in the control group included unstable angina or non-ST-segment elevation myocardial infarction (6 of 16), conduction disorders (3 of 16), hypertensive emergency (3 of ...16), atrial tachyarrhythmia (2 of 16), or stable angina (2 of 16).
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.
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.
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