Gary L Murray
The Heart and Vascular Institute, USA
Title: The impact of ranolazine on left ventricular ejection fraction, autonomic measures, and outcomes in patients with chronic heart failure
Biography
Biography: Gary L Murray
Abstract
Background: Ranolazine (RAN) reduces the late sodium current (INa) in congestive heart failure (CHF), reducing myocardial calcium overload, thereby potentially improving left ventricular (LV) function. RAN also blocks neuronal sodium channel 1.7 (Nav 1.7), potentially altering parasympathetic and sympathetic (P & S) activity.
Objective: The objective of the study is to report RAN’s effect upon LV ejection fraction (LVEF), P & S function, and major adverse cardiac events (MACE) in CHF.
Methods: New York Heart Association (NYHA) class 2-4 CHF patients were given open-label RAN, 1000 mg p.o. b.i.d. (RANCHF, 41 systolic, 13 diastolic) added to guideline-driven therapy, or no adjuvant therapy (NORANCHF, 43 systolic, 12 diastolic). Echocardiographic LVEF was measured at baseline, confirmed by a nuclear multi-gated acquisition (MUGA) study, and reassessed yearly. P & S measures (ANX 3.0, ANSAR, Inc., Philadelphia, PA) were obtained every 6 mo. (mean follow-up 22.8 months), and MACE (cardiac deaths, CHF hospitalizations, ventricular tachycardia [VT]/ventricular fibrillation [VF] therapies) were recorded.
Results: Systolic RANCHF patients’ LVEF increased from 0.30 to 0.36 (p=0.001); diastolic RANCHF patients’ LVEF increased from 0.43 to 0.52 (p=0.002). NORANCHF patients’ LVEF remained unchanged. In RANCHF patients, P & S measures demonstrated improved sympathovagal balance (SB=S/P). SB worsened in NORANCHF subjects. MACE were qualitatively reduced in RANCHF vs. NORANCHF patients: deaths 5.6% vs. 12.7%; CHF admissions 22.2% vs. 27.3%; and VT/VF events 11.1% vs. 23.6%. Of the independent predictors for MACE, SB performed slightly better than LVEF: when SB was ≤2.5 or LVEF was ≥0.32, 80% of subjects were MACE-free; when SB was >2.5, 59% of patients suffered MACE, vs. 50% of patients when LVEF was <0.32.
Conclusion: RAN improves LVEF and autonomic function in CHF patients. RAN qualitatively reduced MACE, and SB performs slightly better than LVEF for prognostication.