Ranolazine Preserves and Improves Left Ventricular Ejection Fraction and Autonomic Measures When Added to Guideline-Driven Therapy in Chronic Heart Failure

Abstract

BackgroundRanolazine (RAN) reduces cardiac sodium channel 1.5’s late sodium current in congestive heart failure (CHF), reducing myocardial calcium overload, potentially improving left ventricular (LV) function. RAN blocks neuronal sodium channel 1.7, potentially altering parasympathetic and sympathetic (P&S) activity. The effects of RAN on LV ejection fraction (LVEF) and P&S function in CHF were studied.MethodsMatched CHF patients were given open-label RAN (1000 mg po-bid) added to guideline-driven therapy (RANCHF, 41 systolic, 13 diastolic) or no adjuvant therapy (control, NORANCHF, 43 systolic, 12 diastolic). Echocardiographic LVEF and P&S measures were obtained at baseline and follow-up (mean 23.7 months).ResultsLVEF increased in 70% of RANCHF patients, an average of 11.3 units. Mean LVEF remained unchanged in NORANCHF patients. P&S measures indicated cardiovascular autonomic neuropathy (P≤0.1 bpm2) in 20% of NORANCHF patients at baseline and in 29% at follow-up (increasing in both groups). At baseline, 28% of patients had high sympathovagal balance (SB), RAN normalized SB over 50% of these; in contrast, the NORANCHF group had a 20% increase in patients with high SB.ConclusionsRAN preserves or improves LVEF and decreases high SB in CHF.

Cardiac metabolism — A promising therapeutic target for heart failure

“…Importantly, a 30-minute ranolazine infusion in patients with HFpEF reduced LVEDP in the RALI-DHF study (Maier, et al, 2013). In another study by Murray and Colombo, up to 70% of patients with HFrEF showed an improvement in EF when treated with ranolazine, compared to no improvement in the noradrenaline treatment arm (Murray & Colombo, 2014).…”

Ranolazine: A true pluripotent cardiovascular drug or jack of all trades, master of none?

“…44 In an open-label trial during which ranolazine was given to patients with either diastolic or systolic heart failure on top of guideline-driven therapy, there appeared to be an improvement in LV systolic function and autonomic measures; however, clinical parameters were not investigated. 45 A prospective single-centre randomised doubleblind placebo-controlled proof-of-concept study termed the Ranolazine for the Treatment of Diastolic Heart Failure (RALI-DHF) study was conducted to determine if ranolazine would be more effective in improving diastolic function among patients with heart failure Table 2: In vitro and in vivo studies investigating the effects of ranolazine on atrial arrhythmia models [51][52][53][54] Author and year of study Study type…”

Triple Versus Double Antianginal Combinations in the Treatment of Patients with Stable Angina with Impaired LV Function: A Single Center Registry

“…[10] Ranolazine preserves and improves left ventricular ejection fraction when added to guideline-directed therapy in patient with chronic heart failure. [11] Ranolazine 500mg bid in chronic coronary patient improves parameters of left ventricular diastolic function as well as improvement in the severity of stable angina. [12] Figueredo et al showed improvement of left ventricular diastolic and systolic function following the administration of ranolazine in patients with stable angina.…”