Effects of Heart Rate Reduction with Ivabradine on Cardio- Pulmonary Capacity in Heart Transplant Recipients

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Background: Sinus tachycardia in heart transplant (HTx) recipients is mainly caused by cardiac denervation. It has been conclusively shown to contribute to limitation of exercise capacity (EC) post transplantation. We assessed the effect of ivabradine on heart rate reduction and respective changes of functional parameters in cardio-pulmonary exercise testing (CPET). Patients and methods: A cohort of 16 HTx recipients (mean age 55 ± 18 years) with sinus rhythm >90/min were prospectively studied while treated with ivabradine (5-10 mg/day). CPET, using a cycle ergometer and a modified Naughton protocol, was performed before and after a median of 6 (interquartile range, 4 - 12) weeks after starting treatment with ivabradine. Results: At a mean of 62 ± 46 days of ivabradine treatment, heart rate was significantly reduced, both for heart rate at rest (from 97 ± 11 to 83 ± 9 /min; P = 0.0011) and during maximum (max.) exercise (from 129 ± 18 to 113 ± 24 /min; P = 0.0072). No significant difference after treatment with ivabradine vs. baseline was observed for any of the functional parameters in CPET, with no changes in oxygen consumption at anaerobic threshold (10.7 ± 3.2 vs. 10.9 ± 2.5 ml/min/kg, P = 0.6417), oxygen consumption at max. exercise (from 14.0 ± 3.1 to 15.2 ± 3.5 ml/ min/kg, P = 0.1477), max. tolerated workload (88.8 ± 25.4 to 90.6 ± 22.2 watt) and ventilatory equivalent for carbon dioxide (EqCO2; 32.7 ± 3.6 to 31.1 ± 3.9, P = 0.0609). Conclusion: We observed a significant reduction in heart rate with ivabradine at rest and at maximum exercise in heart transplant recipients. Functional parameters in CPET were unaffected vs. baseline. We were not able to demonstrate an improvement in EC, possibly due to an impaired training status, a well known multifactorial condition in HTx recipients. The definitive impact of ivabradine on cardiopulmonary capacity requires further investigation and a larger cohort of patients.