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

Background: Ranolazine (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 neuro- nal 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. Methods: Matched 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). Echocar- diographic LVEF and P&S measures were obtained at baseline and follow-up (mean 23.7 months). Results: LVEF 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. Conclusions: RAN preserves or improves LVEF and decreases high SB in CHF.