Abstract
Background: The effect of ranolazine (RAN) on cardiac autonomic balance in congestive heart failure (CHF) was studied. Methods: Fifty-four CHF patients were randomized to (1) open-label RAN (RANCHF) added to usual therapy vs. (2) usual therapy (NORANCHF). Parasympathetic and sympathetic (P&S) measurements were taken at baseline and at 12 months. Results: A total of 16/27 (59%) patients in both groups had initially abnormal P&S measures, including high sympathovagal balance (SB), cardiovascular autonomic neuropathy (CAN) or both. High SB normalized in 10/12 (83%) RANCHF patients vs. 2/11 (18%) NORANCHF patients. SB became high in 5/11 (45%) NORANCHF vs. 1/11 (9%) RANCHF patients. CAN improved in 4/6 (67%) RANCHF patients vs. 5/7 (45%) NORANCHF patients. CAN developed in 1/11 (9%) RANCHF vs. 4/11 (36%) NORANCHF patients. Since improved P&S in RANCHF patients seemed independent of improved brain natriuretic peptide and impedance cardiography (BioZ) measurements, 5 day RAN was given to 30 subjects without CHF but with high SB or CAN. P&S improved in 90% of these subjects. Conclusions: RAN improves unfavorable P&S activity in CHF possibly by a direct effect upon autonomic sodium channels.
Highlights
In congestive heart failure (CHF), there is an increase in the myocardial late sodium current (INa) leading to an intra- cellular calcium (Ca++) overload that causes diastolic dysfunc-tion, microvascular ischemia and early after-depolarizations, increasing the risk of sudden death
An additional potential benefit of RAN in CHF could be improvement in the damaging autonomic dysfunction that it accompanies. This is the first study on changes in parasympathetic and sympathetic (P&S) measures in CHF patients treated with RAN added to guideline-driven therapy
The following variables were recorded: seated resting (5 min) P&S activity (respiratory frequency area (RFa) and lowfrequency area (LFa), respectively) was computed from P&S Monitoring [5,6,7,8,9]; exhalation/inhalation (E/I) ratio and RFa were computed in response to 1 min of deep breathing [9]; Valsalva ratio and LFa were computed in response to a series of short Valsalva maneuvers (≤15 sec); and BP, LFa, RFa and 30:15 ratio were computedin
Summary
In congestive heart failure (CHF), there is an increase in the myocardial late sodium current (INa) leading to an intra- cellular calcium (Ca++) overload that causes diastolic dysfunc-tion, microvascular ischemia and early after-depolarizations, increasing the risk of sudden death. In therapeutic concen- trations, ranolazine (RAN) decreases the rate of INa by 50%, thereby improving this Ca++-related mechanical and electrical dysfunction [1]. RAN potentially could improve the mechanical and electrical dysfunction of CHF. An additional potential benefit of RAN in CHF could be improvement in the damaging autonomic dysfunction that it accompanies. This is the first study on changes in P&S measures in CHF patients treated with RAN added to guideline-driven therapy. The effect of ranolazine (RAN) on cardiac autonomic balance in congestive heart failure (CHF) was studied
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