A Combined-Biomarker Approach to Clinical Phenotyping Renal Dysfunction in Heart Failure

Background: Differentiating heart failure (HF) induced renal dysfunction (RD) from intrinsic kidney disease is challenging. It has been demonstrated that biomarkers such as B-type natriuretic peptide (BNP) or the blood urea nitrogen to creatinine ratio (BUN/creat) can identify high- vs low-risk RD. Our objective was to determine if combining these biomarkers could further improve risk stratification and clinical phenotyping of patients with RD and HF. Methods and Results: A total of 908 patients with a discharge diagnosis of HF were included. Median values were used to define elevated BNP (> 1296 pg/mL) and BUN/creat ( > 17). In the group without RD, survival was similar regardless of BNP and BUN/creat (n = 430, adjusted P = .52). Similarly, in patients with both a low BNP and BUN/creat, RD was not associated with mortality (n = 250, adjusted hazard ratio [HR] = 1.0, 95% confidence interval [CI] 0.6-1.6, P = .99). However, in patients with both an elevated BNP and BUN/creat those with RD had a cardiorenal profile characterized by venous congestion, diuretic resistance, hypotension, hyponatremia, longer length of stay, greater inotrope use, and substantially worse survival compared with patients without RD (n = 249, adjusted HR = 1.8, 95% CI 1.2-2.7, P = .008, P interaction = .005). Conclusions: In the setting of decompensated HF, the combined use of BNP and BUN/creat stratifies patients with RD into groups with significantly different clinical phenotypes and prognosis

The risk of death associated with proteinuria in heart failure is restricted to patients with an elevated blood urea nitrogen to creatinine ratio

Background: Renal dysfunction (RD) is associated with reduced survival in HF; however, not all RD is mechanistically or prognostically equivalent. Notably, RD associated with "pre-renal" physiology, as identified by an elevated blood urea nitrogen to creatinine ratio (BUN/Cr), identifies a particularly high risk RD phenotype. Proteinuria, another domain of renal dysfunction, has also been associated with adverse events. Given that several different mechanisms can cause proteinuria, we sought to investigate whether the mechanism underlying proteinuria also affects survival in HF. Methods and Results: Subjects in the Studies of Left Ventricular Dysfunction (SOLVD) trial with proteinuria assessed at baseline were studied (n = 6439). All survival models were adjusted for baseline characteristics and estimated glomerular filtration rate (eGFR). Proteinuria (trace or 1+) was present in 26% and associated with increased mortality (HR = 1.2; 95% CI, 1.1-1.3, p = 0.006). Proteinuria >1+ was less common (2.5%) but demonstrated a stronger relationship with mortality (HR = 1.9; 95% CI, 1.5-2.5, p <0.001). In patients with BUN/Cr in the top tertile (>= 17.3), any proteinuria (HR = 1.3; 95% CI, 1.1-1.5, p = 0.008) and >1+ proteinuria (HR = 2.3; 95% CI, 1.7-3.3, p <0.001) both remained associated with mortality. However, in patients with BUN/Cr in the bottom tertile (1+ proteinuria (HR = 1.3; 95% CI, 0.79-2.2, p = 0.29, p interaction = 0.036) were not associated with worsened survival. Conclusion: Analogous to a reduced eGFR, the mechanism underlying proteinuria in HF may be important in determining the associated survival disadvantage. (C) 2016 Elsevier Ireland Ltd. All rights reserved

Outcomes Associated With a Strategy of Adjuvant Metolazone or High-Dose Loop Diuretics in Acute Decompensated Heart Failure: A Propensity Analysis

Background-In acute decompensated heart failure, guidelines recommend increasing loop diuretic dose or adding a thiazide diuretic when diuresis is inadequate. We set out to determine the adverse events associated with a diuretic strategy relying on metolazone or high-dose loop diuretics. Methods and Results-Patients admitted to 3 hospitals using a common electronic medical record with a heart failure discharge diagnosis who received intravenous loop diuretics were studied in a propensity-adjusted analysis of all-cause mortality. Secondary outcomes included hyponatremia (sodium = 20% decrease in estimated glomerular filtration rate). Of 13 898 admissions, 1048 (7.5%) used adjuvant metolazone. Metolazone was strongly associated with hyponatremia, hypokalemia, and worsening renal function (P Conclusions-During acute decompensated heart failure, metolazone was independently associated with hypokalemia, hyponatremia, worsening renal function and increased mortality after controlling for the propensity to receive metolazone and baseline characteristics. However, under the same experimental conditions, high-dose loop diuretics were not associated with hypokalemia, hyponatremia, or reduced survival. The current findings suggest that until randomized control trial data prove otherwise, uptitration of loop diuretics may be a preferred strategy over routine early addition of thiazide type diuretics when diuresis is inadequate

Reduced Cardiac Index Is Not the Dominant Driver of Renal Dysfunction in Heart Failure

BACKGROUND: It is widely believed that reduced cardiac index (CI) is a significant contributor to renal dysfunction in patients with heart failure (HF). However, recent data have challenged this paradigm. OBJECTIVES: We sought to determine the relationship between CI and renal function in a multicenter population of HF patients undergoing pulmonary artery catheterization (PAC). METHODS: Patients undergoing PAC in either the randomized or registry portions of the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial were included (n = 575). We evaluated associations between CI and renal function across multiple subgroups and assessed for nonlinear, threshold, and longitudinal relationships. RESULTS: There was a weak but statistically significant inverse correlation between CI and estimated glomerular filtration rate (eGFR), such that higher CI was paradoxically associated with worse eGFR (r = −0.12; p = 0.02). CI was not associated with blood urea nitrogen (BUN) or the BUN to creatinine ratio. Similarly, no significant associations were observed between CI and better renal function across multiple subgroups defined by indications for PAC or hemodynamic, laboratory, or demographic parameters. A nonlinear or threshold effect could not be identified. In patients with serial assessments of renal function and CI, we were unable to find within-subject associations between change in CI and eGFR using linear mixed modeling. Neither CI nor change in CI was lower in patients developing worsening renal function (p ≥ 0.28). CONCLUSIONS: These results reinforce evidence that reduced CI is not the primary driver for renal dysfunction in patients hospitalized for HF, irrespective of the degree of CI impairment or patient subgroup analyzed

Common clinical dilemmas in left ventricular assist device therapy: A glimpse into current trends

Background Left ventricular assist device (LVAD) therapy has been thrust into the forefront of surgical treatment for advanced heart failure (HF). Despite advancements in survival and quality of life with these devices, the multi-disciplinary care for these patients remains far from standardized across institutions. Methods A survey of current practices in LVAD was carried out at the St. Jude Medical User’s meeting representing a variety of caregivers including cardiac surgeons, HF cardiologists, non-HF cardiologists, advanced practice providers and ventricular assist device coordinators, with representation from several continents. Utilizing an audience response system, eleven questions were asked related to the demographics of the audience, left ventricular assist device patient selection and patient management. Results A total of 120 audience members representing both transplant and LVAD centers, destination therapy only LVAD centers and non-implanting, shared care centers across a multitude of disciplines responded to the survey. Questions comprised of patient selection (body mass index, pre-existing renal failure, care giver presence and abstinence from substance abuse) and patient management (anticoagulation regimens, first line therapy for hemolysis, implantable cardioverter-defibrillator usage and route of preferred dialysis) issues. Conclusions LVAD technology will continue to change and improve with the next generation of pumps on the horizon. Progress cannot be made without pausing to understand the current state of technology, practice patterns and patient determinants of success. This survey underscores the lack of consensus regarding best practice principles and the need for an increased focus on care management for LVAD patients with collaborative, multi-institutional studies

Serum dilutions as a predictive biomarker for peri-operative desensitization: An exploratory approach to transplanting sensitized heart candidates.

Antibody-mediated rejection (AMR) of cardiac allografts mediated by anti-HLA Donor Specific Antibodies (DSA) is one of the major barriers to successful transplantation for the treatment of end-stage heart failure. Therapeutic plasma exchange (TPE) is a first-line treatment for pre-transplant desensitization. However, indications for treatment regimens and treatment end-points have not been well established. In this study, we investigated how sera dilutions could guide TPE regimens for effective peri-operative desensitization and early AMR treatment. Our data show that 1:16 dilutions of EDTA-treated sera and 1.5 volume TPE reduce anti-HLA class I and class II antibody levels in the same manner and, therefore, allows to predict which antibodies would respond to peri-operative TPE. We successfully applied this approach to transplanting three highly sensitized cardiac recipients (CPRA 85-93%) with peri-operative desensitization based on a virtual crossmatch performed on 1:16 diluted serum. Furthermore, we have used sera dilutions to guide DSA treatment post-transplant. Although these findings have to be confirmed in a larger prospective study, our data suggest that serum dilutions can serve as a predictive biomarker to guide peri-operative desensitization and post-transplant immunologic management