Usefulness of urinary potassium to creatinine ratio to predict diuretic response in patients with acute heart failure and preserved ejection fraction

Abstract

Background: Patients with acute heart failure (AHF) require intensification in the diuretic strategy. However, the optimal diuretic strategy remains unclear. In this work, we aimed to evaluate the role of urinary potassium to creatinine ratio (K/Cr) to predict diuretic and natriuretic response to thiazide or mineralocorticoid receptor antagonists (MRAs) in a cohort of patients with AHF and preserved ejection fraction (AHF-pEF).

Hypothesis: Patients with a high urinary K/Cr ratio will have a better diuretic and natriuretic response with spironolactone versus chlorthalidone.

Methods: This is a study of 44 patients with AHF-pEF with suboptimal loop diuretic response. The primary endpoint was the baseline K/Cr associated with natriuretic and diuretic effect of chlorthalidone versus spironolactone at 24 and 72 h. Mixed linear regression models were used to analyze the endpoints. Estimates were reported as least squares mean with their respective 95% confidence interval (CIs).

Results: The median age of the study population was 85 years (82.5-88.5), and 30 (68.2%) were women. The inferential multivariate analysis suggested a greater natriuretic and diuretic effect of chlorthalidone across K/Cr levels. In the upper category, chlorthalidone translated into a statistically increase in natriuresis at 24 and 72 h. Chlorthalidone versus spironolactone showed ∆uNa of 25.7 mmol/L at 24 h (95% CI = -3.7 to 55.4, p = .098) and ∆uNa of 24.8 mmol/L at 72 h (95% CI = -4 to 53.6, p = .0106). The omnibus p value is .027. Multivariate analyses revealed a significant increase in 72 h cumulative diuresis irrespective of K/Cr status in those on chlorthalidone.

Conclusions: In patients with AHF-pEF and suboptimal diuretic response, diuresis and natriuresis are higher with the administration of chlorthalidone over spironolactone. These data don't support the hypothesis that the K/Cr ratio can help guide the choice of thiazide diuretic versus MRA in AHF-pEF patients on loop diuretic.

Keywords: acute heart failure; diuretic response; preserved ejection fraction; urinary potassium creatinine ratio.

Figure 1

Flow chart of patients admitted with acute heart failure in the period under study. AHF‐pEF, AHF and preserved ejection fraction; LVEF, left ventricular ejection fraction; uNa, urinary sodium.

Figure 2

Comparison of length of stay among diuretic strategies (chlorthalidone vs. spironolactone).

Figure 3

(A) Comparison of natriuresis among diuretic strategies (chlorthalidone vs. spironolactone) for K/Cr below the median (<0.56). Estimates (least squares means [LSM] with 95% confidence intervals [CI]) derived from linear mixed models for changes in natriuresis according to treatment during the 72 h follow‐up period, including the treatment x visit interaction term (24 and 72 h visits), and adjusted for urinary sodium (uNa) at baseline, age, total dose of furosemide, and baseline glomerular filtration rate. The upper section of the bar charts represents the LSM value, and the upper and lower limits of the lines represents the corresponding 95% CI. (B) Comparison of natriuresis among diuretic strategies (chlorthalidone vs. spironolactone) for K/Cr equal to or above the median (≥0.56). Estimates (LSM with 95% CI) derived from linear mixed models for changes in natriuresis according to treatment during the 72 h follow‐up period, including the treatment x visit interaction term (24 and 72 h visits), and adjusted for uNa at baseline, age, total dose of furosemide, and baseline glomerular filtration rate. The upper section of the bar charts represents the LSM value, and the upper and lower limits of the lines represents the corresponding 95% CI. K/Cr, urinary potassium to creatinine ratio.