By Van Selby, MD
Assistant Professor of Medicine, University of California, San Francisco, Cardiology Division, Advanced Heart Failure Section
Dr. Selby reports no financial relationships relevant to this field of study.
SYNOPSIS: In a retrospective analysis of patients with acute decompensated heart failure who received a pulmonary artery catheter, there was no significant correlation between cardiac index and markers of renal function, contradicting the importance of cardiac output in renal dysfunction among patients with heart failure.
SOURCE: Hanberg JS, Sury K, Wilson FP, et al. Reduced cardiac index is not the dominant driver of renal dysfunction in heart failure. J Am Coll Cardiol 2016;67:2199-2208.
Renal dysfunction is common among patients hospitalized for heart failure (HF) and associated with a worse prognosis. Many believe reduced cardiac index (CI) is the primary cause of worsening renal function. However, several small studies have suggested CI is not correlated with renal function in HF. No study has thoroughly evaluated the relationship between CI and markers of renal dysfunction in a large, heterogeneous, acute HF population.
Investigators analyzed data from 575 patients enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) study who received a pulmonary artery catheter (PAC) to guide management of acute decompensated HF. Patients were included whether they were enrolled through the randomized ESCAPE trial or the concurrent PAC registry. The mean ejection fraction was 23%, mean CI was 2.3 L/min/m2, and mean estimated glomerular filtration rate (eGFR) at baseline was 52.4 mL/min/1.73 m2. Researchers measured the correlation between CI and eGFR at baseline and evaluated the relationship between changes in CI and eGFR over time.
The overall correlation between baseline CI and eGFR was weak, and higher CI was actually correlated with lower eGFR (r = -0.12; P = 0.02). There was no correlation between CI and eGFR in a broad range of subgroups, including patients with advanced symptoms, worse renal function, or inotrope dependence. Longitudinal changes in renal function were not associated with individual measurements of CI or change in CI over time. In a multivariate analysis, both higher right atrial pressure and higher CI were associated with lower GFR, although hemodynamic predictors accounted for a tiny amount of the observed eGFR variability. The authors concluded that low cardiac output is not the predominant driver for renal dysfunction in patients with decompensated HF.
The complex relationship between the heart and kidneys in HF patients remains incompletely understood. The concept of decreases in CI driving worsening renal function seems intuitive to many clinicians. The eGFR is related to the product of renal blood flow and the filtration fraction. Therefore, any factor that reduces overall perfusion (i.e., cardiac index) should reduce the eGFR. This is the largest and one of the most thorough studies to date evaluating the relationship between CI and renal dysfunction and demonstrates convincingly that CI is not the primary driver of renal dysfunction in HF. This is primarily due to renal autoregulation that maintains renal perfusion over a wide range of hemodynamic conditions. Changes in the CI do not have a strong effect on renal blood flow, therefore maintaining eGFR.
The authors impressively used subgroup analyses and longitudinal changes in CI to re-enforce the finding that low CI does not drive renal dysfunction. There was not a single clinical or hemodynamic subset of patients in whom CI and eGFR were positively correlated, including patients with very low CI. Additionally, it also is worth noting the lack of a relationship between CI and renal dysfunction observed in patients referred for PAC placement specifically to evaluate and manage oliguric renal failure. Furthermore, researchers demonstrated that neither baseline nor changes in CI predicts worsening renal function during hospitalization for HF.
So which hemodynamic factors drive renal function in HF? Several studies have identified systolic blood pressure, an important determinant of renal blood flow, as the strongest predictor of renal dysfunction, with the relationship maintained independent of CI. Both the central venous pressure and intra-abdominal pressure contribute to renal venous pressure, and also have been identified as important determinants of GFR in HF. Therefore, factors that alter the perfusion pressure across the kidneys, whether it be lower arterial pressure or higher renal venous pressure, appear to be much more important than the CI in determining eGFR. Increased neurohormonal activation, particularly the sympathetic and renin-angiotensin systems, also plays a role.
There are several limitations to this study. Serum creatinine, which was used to estimate GFR for the primary outcome, is an imperfect measure of renal function. This may be true especially in the decompensated HF population. Creatinine also primarily reflects glomerular filtration and does not account for changes in other components of renal function, such as tubular function.
Although this was not a study of treatment strategies for acute HF, we can make several conclusions based on the findings. First, the practice of starting or uptitrating inotropes to correct renal dysfunction in HF may not be an effective strategy. Similarly, right heart catheterization should not be used indiscriminately to evaluate worsening renal function in patients with acute HF. Rather, efforts to avoid or minimize hypotension and decrease the central venous pressure are more likely to restore perfusion pressure and improve renal function.