BACKGROUND: Heart failure with preserved ejection fraction (HFpEF), formerly 
referred to as diastolic heart failure (DHF), accounts for >50% of all HF 
patients. So far, there has been no specific treatment for impaired left 
ventricular (LV) relaxation. Data from in vitro and animal studies indicate that 
ranolazine improves diastolic function by inhibiting the late sodium current.
HYPOTHESIS: RAnoLazIne for the Treatment of Diastolic Heart Failure (RALI-DHF) 
is a prospective, single-center, randomized, double-blind, placebo-controlled 
proof-of-concept study to determine if ranolazine compared with placebo will be 
more effective in improving diastolic function in patients with HFpEF.
METHODS: Twenty patients with HFpEF (EF ≥ 50% and ratio of transmitral Doppler 
early filling velocity to tissue Doppler early diastolic mitral annular velocity 
[E/E'] >15 or N-terminal pro-type brain natriuretic peptide >220 pg/mL) will be 
randomized to receive ranolazine or placebo in a 1.5:1 ratio during their 
catheterization if the LV end-diastolic pressure is ≥18 mm Hg and the time 
constant of relaxation (τ) is ≥50 ms. Treatment will consist of intravenous 
infusion of study drug (or placebo) for 24 hours, followed by oral treatment for 
a total of 14 days.
ENDPOINTS: The study will include the following exploratory endpoints: (1) 
change from baseline to 30 minutes from initiation of intravenous study drug 
administration during cardiac catheterization hemodynamic parameters at both 
resting and paced (120 beats per minute) conditions: τ, LV end-diastolic 
pressure, and dP/dt(min) .; and (2) change from baseline to day 14 in E/E', 
maximal oxygen consumption, and N-terminal pro-type brain natriuretic peptide.
CONCLUSIONS: The RALI-DHF study is designed as a translational study to bridge 
the gap between basic science and therapeutics and to determine if ranolazine, 
compared with placebo, will be more effective in improving diastolic function in 
patients with HFpEF.