Gallet Romain, Ternacle Julien, Damy Thibaud, Guendouz Soulef, Bremont Camille, Seemann Aurélien, Gueret Pascal, Dubois-Rande Jean-Luc, Lim Pascal
AP-HP - University Hospital Henri Mondor, Cardiovascular Department, INSERM U955 Team 3, Creteil, France.
AP-HP - University Hospital Henri Mondor, Cardiovascular Department, INSERM U955 Team 3, Creteil, France.
Int J Cardiol. 2014 Sep 20;176(2):450-5. doi: 10.1016/j.ijcard.2014.07.093. Epub 2014 Aug 1.
Dobutamine induced tachycardia increases myocardial oxygen consumption and impairs ventricular filling. We hypothesized that Ivabradine may be efficient to control dobutamine induced tachycardia.
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.
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).
This pilot study demonstrates the safety and potential benefit of a HR lowering agent in cardiogenic shock.
多巴酚丁胺诱发的心动过速会增加心肌耗氧量并损害心室充盈。我们推测伊伐布雷定可能有效控制多巴酚丁胺诱发的心动过速。
我们评估了伊伐布雷定联合多巴酚丁胺对稳定型心力衰竭（HF）患者（左心室射血分数[LVEF]<35%，n = 22，试验人群）的影响，并在有心脏辅助或移植禁忌证的难治性心源性休克患者（n = 9，验证人群）中验证了其效果。在试验人群（62±17岁，LVEF = 24±8%）中，在静息状态下以及使用多巴酚丁胺[10μg/min]时、口服伊伐布雷定[5mg]前后评估收缩和舒张功能。在验证人群（54±11岁，LVEF = 22±7%）中，将伊伐布雷定[5mg，每日两次]添加到多巴酚丁胺输注中。
在试验人群中，伊伐布雷定降低了静息时和多巴酚丁胺超声心动图检查期间的心率[HR]（-9±8次/分钟，P = 0.0004）。心率降低与心脏输出功率降低以及静息时舒张期时长增加（+74±67毫秒，P = 0.0002）和多巴酚丁胺输注期间增加（+75±67毫秒，P<0.0001）相关。多巴酚丁胺治疗期间LVEF的变化在伊伐布雷定治疗后比治疗前更大（+7.2±4.7%对+3.6±4.2%，P = 0.002）。在验证人群中，伊伐布雷定降低了HR（-18±11次/分钟，P = 0.008）并改善了舒张期充盈时间（+67±42毫秒，P = 0.012），而没有降低心输出量。在24小时时，伊伐布雷定改善了收缩压（+9±5mmHg，P = 0.007）、每日尿量（+0.7±0.5L，P = 0.008）、氧平衡（ΔScvO2 = +13±15%，P = 0.010）和N末端脑钠肽前体（-2270±1912pg/mL，P = 0.017）。最后，只有2/9（22%）的患者死亡，而根据历史队列确定的预期死亡率为78%（P = 0.017）。
这项初步研究证明了心率降低药物在心源性休克中的安全性和潜在益处。
