RAnoLazIne for the treatment of diastolic heart failure in patients with preserved ejection fraction: the RALI-DHF proof-of-concept study.

Abstract

OBJECTIVES:

This study investigated whether inhibiting late Na(+) current by using ranolazine improved diastolic function in patients with heart failure with preserved ejection fraction (HFpEF).

BACKGROUND:

HFpEF accounts for >50% of all HF patients, but no specific treatment exists.

METHODS:

The RALI-DHF (RAnoLazIne for the Treatment of Diastolic Heart Failure) study was a prospective, randomized, double-blind, placebo-controlled small proof-of-concept study. Inclusion criteria were EF ≥45%, a mitral E-wave velocity/mitral annular velocity ratio (E/E') >15 or N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration >220 pg/ml, a left ventricular end-diastolic pressure (LVEDP) ≥18 mm Hg, and time-constant of relaxation (tau) ≥50 ms. Patients were randomized to ranolazine (n = 12) or placebo (n = 8). Treatment consisted of intravenous infusion for 24 h, followed by oral treatment for 13 days.

RESULTS:

After 30 min of infusion, LVEDP (p = 0.04) and pulmonary capillary wedge pressure (p = 0.04) decreased in the ranolazine group but not in the placebo group. Mean pulmonary artery pressure showed a trend toward a decrease in the ranolazine group that was significant under pacing conditions at 120 beats/min (p = 0.02), but not for the placebo group. These changes occurred without changes in left ventricular end-systolic pressure or systemic or pulmonary resistance but in the presence of a small but significant decrease in cardiac output (p = 0.04). Relaxation parameters (e.g., tau, rate of decline of left ventricular pressure per minute [dP/dtmin]) were unaltered. Echocardiographically, the E/E' ratio did not significantly change after 22 h. After 14 days of treatment, no significant changes were observed in echocardiographic or cardiopulmonary exercise test parameters. There were no significant effects on NT-pro-BNP levels.

CONCLUSIONS:

Results of this proof-of-concept study revealed that ranolazine improved measures of hemodynamics but that there was no improvement in relaxation parameters. (Ranolazine in Diastolic Heart Failure [RALI-DHF]; NCT01163734).

• Authors: Lars S Maier, Beth Layug, Ewa Karwatowska-Prokopczuk, Luiz Belardinelli, Stella Lee, Julia Sander, Christian Lang, Rolf Wachter, Frank Edelmann, Gerd Hasenfuss, Claudius Jacobshagen
• Journal: JACC. Heart failure (JACC Heart Fail) Vol. 1 Issue 2 Pg. 115-22 (Apr 2013) ISSN: 2213-1787 [Electronic] United States
• PMID: 24621836 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Acetanilides
• Piperazines
• Sodium Channel Blockers
• Ranolazine

Topics

• Acetanilides (therapeutic use)
• Aged
• Double-Blind Method
• Female
• Heart Failure, Diastolic (drug therapy, physiopathology)
• Humans
• Male
• Piperazines (therapeutic use)
• Prospective Studies
• Ranolazine
• Sodium Channel Blockers (therapeutic use)
• Stroke Volume