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

Gary L Murray,Joseph Colombo

doi:10.31579/2641-0419/046

Gary L Murray, Joseph Colombo

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https://doi.org/10.31579/2641-0419/046

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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.

Highlights

Despite advances in pharmacologic management [1,2,3,4,5] and device therapy [6], improvement in left ventricular (LV) function in congestive heart failure (CHF) patients, while statistically significant, remains relatively mild in many sub- jects
RAN may directly alter function of the parasympathetic and sympathetic (P&S) branches of the autonomic nervous system (ANS). We postulated these actions of RAN should result in favorable changes in LV func- tion and P&S measures in CHF
Since LV ejection fraction (LVEF) is widely accepted as one of the most important prognostic indicators in CHF [30], we focused on its changes after RAN was added to guideline-driven therapy

Summary

Introduction

Despite advances in pharmacologic management [1,2,3,4,5] and device therapy [6], improvement in left ventricular (LV) function in congestive heart failure (CHF) patients, while statistically significant, remains relatively mild in many sub- jects. RAN binds to amino acid F1760 of the cardiac sodium channel 1.5 (Nav1.5), thereby reducing the late INa. In a therapeutic concentration (6 μmol), intra- myocardial Ca++ overload is reduced 50%. RAN may directly alter function of the parasympathetic and sympathetic (P&S) branches of the autonomic nervous system (ANS). We postulated these actions of RAN should result in favorable changes in LV func- tion and P&S measures in CHF. 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. 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). Conclusions: RAN preserves or improves LVEF and decreases high SB in CHF

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