Abstract 2578: The Selective If Channel Antagonist Ivabradine in Stable Patients after Heart Transplantation (HTX)
Due to allograft denervation practically all heart transplant recipients have a significantly elevated heart rate associated with considerable discomfort. Pharmacologic heart rate reduction with β blockers or calcium channel blockers may negatively affect exercise capacity and can be associated with adverse drug effects. The If channel antagonist Ivabradine offers an opportunity for selective heart rate reduction that has not previously been studied in heart transplant recipients. 17 patients were studied (2 female, 15 male, age 53.4 +- 9.0 years, time post HTX 4.0 +- 3.5 years). Patients were on stable doses of immunosuppression, with either Mycophenolate Mofetile (MMF)/Cyclosporine A or Tacrolimus/MMF. Heart rate (24h Holter monitoring), exercise capacity (bicycle spiroergometry) and Quality of Life (questionnaire) were assessed consecutively under no medication, β blocker therapy (metoprolol succinate; target dose: 190 mg/day), and treatment with Ivabradine (target dose: 15 mg/day). Ivabradine dose was carefully escalated over a 3-week period, adverse effects were noted in 41% of patients on β blocker (requiring drug discontinuation in 1 patient) and 25% on Ivabradine. At baseline mean heart rate was 97.8 +- 7.1 bpm. After 8 weeks of β blocker treatment mean heart rate was reduced to 85 +- 9.4 bpm (p<0.01 vs. baseline) compared to Ivabradine with 77.3 +-7.5 bpm (p<0.01 vs. baseline and vs. β blocker). Exercise capacity was unchanged by either treatment form (VO2max baseline 19.8 +- 5.5, β blocker 21.2 +- 5.5, Ivabradine 20.25 +-4.6 ml/min, p=n.s.). Heart rate reduction was preferred over no treatment by 41% of patients with β blocker and 82% on Ivabradine. Excessive heart rate reduction due to potential CYP3A4 inhibition was not seen. No changes were observed in immunosuppressive drug dosage or blood levels, blood pressure and renal or liver function tests. Heart rate reduction with Ivabradine appears to be effective, safe and potentially better tolerated than β blocker therapy in heart transplant recipients. In the majority of patients no limiting effects on exercise capacity were seen and lower heart rate was appreciated. While the prognostic significance of heart rate after HTX is still unknown, Ivabradine may offer relevant symptomatic benefit.