title: Ranolazine for the treatment of heart failure with preserved ejection fraction: background, aims, and design of the RALI-DHF study.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Cardiology and Pneumology, Georg-August-University, Robert-Koch-Strasse 40, Göttingen, Germany.
authors.forename: Claudius
authors.initials: C
authors.lastname: Jacobshagen
authors.forename: Luiz
authors.initials: L
authors.lastname: Belardinelli
authors.forename: Gerd
authors.initials: G
authors.lastname: Hasenfuss
authors.forename: Lars S
authors.initials: LS
authors.lastname: Maier
mesh_terms: D000083:Acetanilides / Q000008:administration & dosage / Q000627:therapeutic use*; D000284:Administration, Oral; D015415:Biomarkers / Q000097:blood; D006328:Cardiac Catheterization; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D015150:Echocardiography, Doppler; D005858:Germany; D054144:Heart Failure, Diastolic / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007262:Infusions, Intravenous; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D010446:Peptide Fragments / Q000097:blood; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D015990:Placebo Effect; D011446:Prospective Studies; D000069458:Ranolazine; D020127:Recovery of Function; D012107:Research Design; D013318:Stroke Volume; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D000083:Acetanilides; D015415:Biomarkers; D002317:Cardiovascular Agents; D010446:Peptide Fragments; D010879:Piperazines; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000069458:Ranolazine