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

Abstract

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.

Pulmonary Catherization Data Correlate Poorly with Renal Function in Heart Failure

“…Comprehensively, our results are consistent with findings represented in prior, smaller studies of similar scope and design [7, 8, 17, 19] in both outcome and effect size. Our study is of interest in that it is the largest of its kind by far, captures a population of patients with only advanced heart failure, and represents patients across all major medical centers within the USA.…”

“…This paradoxical result was unexpected and whilst the correlation coefficient was extremely small, it was consistent throughout subgroups within this study. Hanberg et al [7] and Dammen et al [15], in similarly designed studies, also found such a paradoxical association. This analysis adds to the literature on this issue, suggesting it may indeed represent in vivo phenomena of unclear significance.…”

“…The former refers to the notion that decreases in cardiac index (CI) result in inadequate renal perfusion and ultimately organ dysfunction. However clinical trials aimed at improving CI with inotropic therapy such as the ROSE trial [6] and large observational series [7-10] have increasingly failed to support this theory, the latter finding no notable epidemiologic association between baseline CI and renal dysfunction.…”

“…Those that do are often small in size. Some analyses from the ESCAPE trial have suggested no association between renal failure and any pulmonary artery catherization hemodynamic value [8, 13], whilst other observational series suggest weak associations between renal failure and cardiac congestion [7, 9, 10, 14, 15]. Damman et al [15] demonstrated in the largest series on this topic by far ( n = 2,557 patients) an inverse relationship in terms of cardiac filling pressures, predominantly renal artery pressure, with renal function.…”

Intrarenal venous flow in cardiorenal syndrome: a shining light into the darkness

“…1,2 However, there is a lack of well-stablished tools for distinguishing between both haemodynamic phenotypes. However, recent evidence has challenged this notion and postulate venous renal congestion as a key component of the cardiorenal interaction in ADHF.…”