Increased Sympathetic Tone in Congestive Heart Failure and Comorbid PainAcute Friend Turns Chronic Foe and a Novel Pharmacologic Corrective Approach

Acute pain and congestive heart failure (CHF) both increase sympathetic (S) tone, decreasing pain and improving cardiac output. However, chronically high S increases pain and worsens CHF. Mechanisms will be discussed, and off-label ranolazine is a novel potential pharmacologic remedy in chronic CHF: (1) Fifty-four CHF patients were randomized to adjunctive RAN (RANCHF, 1000mg bid) vs. NORANCHF. Autonomic measurements (ANX 3.0 Autonomic Monitor) were taken at baseline and 1 yr. Fifty-nine % of patients in both groups were initially abnormal, including high sympathovagal balance (SB) that normalized in 10/12 (83%) RANCHF patients vs. 2/11 (18%) NORANCHF patients. High SB developed in 5/11 (45%) NORANCHF vs. 1/11(9%) RANCHF patients; (2) Matched CHF patients were given adjunctive RAN (1000 mg po-bid) (RANCHF, 41 systolic, 13 diastolic) vs. NORANCHF (43 systolic, 12 diastolic). Echocardiographic LVEF and autonomic measures were obtained at baseline and follow-up (mean 23.7 months). LVEF increased in 70% of RANCHF patients, an average of 11.3 units. Mean LVEF remained unchanged in NORANCHF patients. At baseline, 28% of patients had high SB. RAN normalized SB in >50%; the NORANCHF group had a 20% increase in patients with high SB. RAN reduced (composite endpoint) CHF admissions, cardiac death, ventricular tachycardia/fibrillation[vt/vf] by 40 % In conclusion, RAN substantially corrects the maladaptive SNS CHF response. Since 1 mechanism of action of RAN is a strongly use-dependent inhibition of the Nav1.7 in S ganglia, RAN should provide pain relief in chronically S-mediated pain syndromes.