Hemodynamic effects of Ivabradine in addition to dobutamine in patients with severe systolic dysfunction

Background: Dobutamine induced tachycardia increases myocardial oxygen consumption and impairs ventricular filling. We hypothesized that Ivabradine may be efficient to control dobutamine induced tachycardia.

Methods: We assessed the effects of Ivabradine in addition to dobutamine in stable heart failure (HF) patients (LVEF < 35%, n = 22, test population) and validated its effects in refractory cardiogenic shock patients (n = 9, validation population) with contraindication to cardiac assistance or transplant. In the test population (62 ± 17 years, LVEF = 24 ± 8%), systolic and diastolic function were assessed at rest and under dobutamine [10 γ/min], before and after Ivabradine [5mg per os]. In the validation population (54 ± 11 years, LVEF = 22 ± 7%), Ivabradine [5mg twice a day] was added to the dobutamine infusion.

Results: In the test population, Ivabradine decreased heart rate [HR] at rest and during dobutamine echocardiography (-9 ± 8 bpm, P = 0.0004). The decrease in HR was associated with a decrease in cardiac power output and an increase in diastolic duration at rest (+ 74 ± 67 ms, P = 0.0002), and during dobutamine infusion (+ 75 ± 67 ms, P < 0.0001). Change in LVEF during dobutamine was greater after Ivabradine treatment than before (+ 7.2 ± 4.7% vs. + 3.6 ± 4.2%, P = 0.002). In the validation population, Ivabradine decreased HR (-18 ± 11 bpm, P = 0.008) and improved diastolic filling time (+ 67 ± 42 ms, P = 0.012) without decreasing cardiac output. At 24h, Ivabradine improved systolic blood pressure (+ 9 ± 5 mmHg, P = 0.007), daily urine output (+ 0.7 ± 0.5L, P = 0.008), oxygen balance (ΔScv02 = + 13 ± 15%, P = 0.010), and NT-pro BNP (-2270 ± 1912 pg/mL, P = 0.017). Finally, only 2/9 (22%) patients died whereas expected mortality determined from a historical cohort was 78% (P = 0.017).

Conclusion: This pilot study demonstrates the safety and potential benefit of a HR lowering agent in cardiogenic shock.