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

Abstract

Background: It is widely believed that a 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: This study 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 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 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.

Keywords: blood urea nitrogen; cardiorenal; creatinine; pulmonary artery catheterization; renal function.

Figure 1. eGFR and CI in the Overall Population

In this scatterplot of all available pairs of cardiac index (CI) and estimated glomerular filtration rate (eGFR) per patient, no association between CI and eGFR was observed. Compared with linear regression, neither 3-knot spline (p = 0.06), 4-knot spline (p = 0.08), nor fractional polynomial (p = 0.06) demonstrated a better fit to the data.

Figure 2. Relative Change in eGFR against CI Measures

Scatterplots of relative change are seen compared to baseline cardiac index (A), last measured CI (B), CI on physician-determined optimal day (C), and change in CI (D) in the ESCAPE trial. p≥0.31 for all associations. ESCAPE = Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness; other abbreviations as in Figure 1.

Figure 3. Relationship between CI and Markers of Decongestion

There was no significant association between relative change in hemoglobin and baseline CI (median value: 1.9 l/min/m²; p = 0.45) or between diuretic efficiency and baseline CI (p = 0.59). Abbreviations as in Figure 1.