RAnoLazIne for the Treatment of Diastolic Heart Failure in Patients With Preserved Ejection Fraction: The RALI-DHF Proof-of-Concept Study

2013 | journal article; research paper. A publication with affiliation to the University of Göttingen.

Jump to: Cite & Linked | Documents & Media | Details | Version history

Cite this publication

​RAnoLazIne for the Treatment of Diastolic Heart Failure in Patients With Preserved Ejection Fraction: ​The RALI-DHF Proof-of-Concept Study​
Maier, L. S. ; Layug, B.; Karwatowska-Prokopczuk, E.; Belardinelli, L.; Lee, S.; Sander, J. & Lang, C. et al.​ (2013) 
JACC: Heart Failure1(2) pp. 115​-122​.​ DOI: https://doi.org/10.1016/j.jchf.2012.12.002 

Documents & Media

License

GRO License GRO License

Details

Authors
Maier, Lars S. ; Layug, Beth; Karwatowska-Prokopczuk, Ewa; Belardinelli, Luiz; Lee, Stella; Sander, Julia; Lang, Christian; Wachter, Rolf ; Edelmann, Frank ; Hasenfuss, Gerd ; Jacobshagen, Claudius 
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, doubleblind, 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/dt(min)]) 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) (C) 2013 by the American College of Cardiology Foundation
Issue Date
2013
Journal
JACC: Heart Failure 
Project
SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz 
SFB 1002 | A03: Bedeutung CaMKII-abhängiger Mechanismen für die Arrhythmogenese bei Herzinsuffizienz 
SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur 
Working Group
RG Hasenfuß (Transition zur Herzinsuffizienz) 
RG L. Maier (Experimentelle Kardiologie) 
ISSN
2213-1779
eISSN
2213-1787
Language
English

Reference

Citations


Social Media