Libin Cardiovascular Institute of Alberta, Cummings School of Medicine, University of Calgary, Calgary, Alberta, Canada.
ESC Heart Fail. 2019 Oct;6(5):1088-1091. doi: 10.1002/ehf2.12499. Epub 2019 Jul 23.
Ivabradine is a selective sinus node inhibitor indicated in patients with symptomatic chronic heart failure on stable guideline-recommended heart failure therapy including appropriate doses of beta-blockers. The use in cardiogenic shock remains off label and has been considered a contraindication due to the theoretical risk of attenuating compensatory tachycardia. Tachycardia, especially in the context of inotropic therapy, may be deleterious, resulting in increased myocardial oxygen consumption and reduction in diastolic filling. As ivabradine does not have negative inotropic action, it may present a potential means to manage tachycardia in cardiogenic shock. We present a case series of four patients with cardiogenic shock started on ivabradine who were unable to tolerate beta-blockers.
Five patients identified with cardiogenic shock defined as a severe reduction in cardiac index (<2.0 L/min/m ) and elevated filling pressures on inotropic therapy were started on ivabradine in patients with sinus tachycardia [heart rate (HR) >100] who were intolerant to beta-blockers. Each patient had a cardiac magnetic resonance imaging, echocardiogram, and coronary angiogram for determination of aetiology. Invasive haemodynamics via pulmonary artery catheterization were measured during initiation and titration of ivabradine (baseline, 6, 12, 24, and 48 h after ivabradine administration) with continuous telemetry monitoring for any dysrhythmia or bradyarrhythmias. All patients tolerated ivabradine initiation, and at 24 h, an observed decrease in HR (106 ± 6.8 vs. 91.6 ± 6.4 b.p.m., P = 0.04), pulmonary arterial occlusion pressure (30.4 ± 4.8 vs. 24 ± 5.1 mmHg, P = 0.04), and right atrial pressure (16.8 ± 6.2 vs. 9 ± 4.3 mmHg, P = 0.0002). An improvement was observed in mixed venous oxygen saturation (SvO ) (51 ± 8.8 vs. 64.8 ± 5.3%, P < 0.04), stroke volume (37.2 ± 7.6 vs. 49.2 ± 12.9 mL, P < 0.04), and right and left ventricular stroke work index (Table 1). No significant changes were observed with mean arterial pressure (73.4 ± 7.5 vs. 75.8 ± 5.0 mmHg, P = 0.81) and thermodilution-derived cardiac index (1.7 ± 0.2 vs. 2.5 ± 0.7 L/min/m , P = 0.58). Inotropic support was weaned successfully in three of five patients (88 ± 30 h) with subsequent titration of beta-blocker therapy. Two patients improved clinically but ultimately required left ventricular assist device implantation. All patients were discharged alive from hospital at 17 ± 7.9 days following ivabradine initiation.
In our small non-randomized series of patients in cardiogenic shock, ivabradine was safely used to reduce HR in patients previously intolerant of beta-blockade. There are limited data surrounding the use of ivabradine in cardiogenic shock, and future studies should be undertaken to determine the optimal HR in humans with cardiogenic shock and whether systematic limitation of peak HR may improve outcomes.
依伐布雷定是一种选择性窦房结抑制剂，适用于在稳定接受指南推荐的心力衰竭治疗（包括适当剂量的β受体阻滞剂）的症状性慢性心力衰竭患者。在心源性休克中的应用仍然是超适应证的，由于理论上可能会减弱代偿性心动过速，因此被认为是禁忌证。心动过速，尤其是在正性肌力治疗的情况下，可能是有害的，导致心肌耗氧量增加和舒张充盈减少。由于依伐布雷定没有负性肌力作用，因此它可能为管理心源性休克中的心动过速提供一种潜在手段。我们报告了 4 例因不耐受β受体阻滞剂而开始使用依伐布雷定的心源性休克患者的病例系列。
在开始使用依伐布雷定时，我们确定了 5 例心源性休克患者，其定义为心指数严重降低（<2.0 L/min/m ），在正性肌力治疗时充盈压升高，并伴有窦性心动过速[心率（HR）>100]。每位患者均进行了心脏磁共振成像、超声心动图和冠状动脉造影，以确定病因。通过肺动脉导管测量有创血流动力学，在开始和滴定依伐布雷定时进行测量（基线、6、12、24 和 48 小时后给予依伐布雷定），并进行连续遥测监测任何心律失常或心动过缓。所有患者均耐受依伐布雷定的起始治疗，在 24 小时时，观察到 HR 下降（106±6.8 比 91.6±6.4 b.p.m.，P=0.04）、肺动脉闭塞压（30.4±4.8 比 24±5.1 mmHg，P=0.04）和右心房压（16.8±6.2 比 9±4.3 mmHg，P=0.0002）下降。混合静脉血氧饱和度（SvO ）（51±8.8 比 64.8±5.3%，P<0.04）、每搏量（37.2±7.6 比 49.2±12.9 mL，P<0.04）和右、左心室每搏功指数（表 1）均有所改善。平均动脉压（73.4±7.5 比 75.8±5.0 mmHg，P=0.81）和热稀释法心指数（1.7±0.2 比 2.5±0.7 L/min/m ，P=0.58）无显著变化。5 例患者中的 3 例（88±30 小时）成功地减少了正性肌力药物的支持，随后减少了β受体阻滞剂的治疗。2 例患者的临床情况有所改善，但最终需要左心室辅助装置植入。所有患者在开始使用依伐布雷定后 17±7.9 天出院，均存活。
在我们的小非随机心源性休克患者系列中，依伐布雷定安全地用于降低先前不耐受β受体阻滞剂的患者的 HR。在心源性休克中使用依伐布雷定的数据有限，应该进行未来的研究，以确定心源性休克患者的最佳 HR，以及是否系统限制峰值 HR 可以改善结局。
