HEMODYNAMIC AND CLINICAL LIMITATIONS OF LONG-TERM INOTROPIC THERAPY WITH AMRINONE IN PATIENTS WITH SEVERE CHRONIC HEART-FAILURE
HEMODYNAMIC AND CLINICAL LIMITATIONS OF LONG-TERM INOTROPIC THERAPY WITH AMRINONE IN PATIENTS WITH SEVERE CHRONIC HEART-FAILURE
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DOI：
10.1161/01.cir.70.6.1038
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发表时间：
1984-01-01
期刊：
影响因子：
37.8
通讯作者：
YUSHAK, M
中科院分区：
文献类型：
--
作者：
PACKER, M;MEDINA, N;YUSHAK, M
为了确定长期正性肌力刺激对心肌的血流动力学和临床影响，31例严重慢性心力衰竭患者接受口服氨力农（每日600 mg）治疗，并在短期和长期治疗期间进行侵入性血流动力学研究。每搏输出量和每搏作功指数在治疗的最初48小时内显著增加（P < 0.01），但2-10 wk后恢复至治疗前水平;停药后，这两个变量迅速恶化，其值显著低于氨力农治疗前观察到的值左室充盈压、平均动脉压和体循环阻力值相似，但差异有显著性（P < 0.01）。这种反应模式表明，在氨力农治疗期间发生了基础心脏病的进展，并对其未能产生长期益处做出了重要贡献。左心室功能障碍的进展与心率和血浆肾素活性的进行性增加以及血清钠浓度的下降相关。临床上，氨力农治疗并发4例患者持续症状性室性心动过速，4例患者心肌缺血恶化，8例患者充血性心力衰竭恶化，所有患者在进入研究前均稳定; 31例患者中仅3例临床改善。10例患者在治疗的前2周死亡，16例（52%）在3个月内死亡，死亡率是血管扩张药物的两倍。虽然非心脏不良反应是常见的，他们不是药物失败的主要原因。氨力农长期治疗可能会加速左心室功能障碍的进展，加剧心肌缺血并引发危及生命的室性快速性心律失常，从而缩短严重慢性心力衰竭患者的生存期。长时间使用正性肌力药物可能会以损害心肌的长期效应为代价而获得短期获益。
To determine the hemodynamic and clinical effects of long-term positive inotropic stimulation on the myocardium, 31 patients with severe chronic heart failure were treated with oral amrinone (600 mg daily) and invasive hemodynamic studies were performed during short- and long-term treatment with the drug. Stroke volume and stroke work indexes increased markedly during the first 48 h of therapy (P < 0.01) but returned to pretreatment values after 2-10 wk; upon drug withdrawal, both variables deteriorated rapidly to values significantly lower than those observed before treatment with amrinone (P < 0.01), despite similar values for left ventricular filling pressure, mean arterial pressure and systemic vascular resistance. This pattern of response indicated that progression of the underlying heart disease had occurred during treatment with amrinone and contributed importantly to its failure to produce long-term benefits. Progression of left ventricular dysfunction was associated with a progressive increase in heart rate and plasma renin activity and a decline in serum Na concentration. Clinically, amrinone therapy was complicated by sustained symptomatic ventricular tachycardia in 4 patients, worsening myocardial ischemia in 4 patients and worsening congestive heart failure in 8 patients, all of whom had been stable before entry into the study; only 3 of the 31 patients improved clinically. Ten patients died during the first 2 wk of treatment, and 16 (52%) were dead within 3 mo., a mortality rate twice as great as that seen during comparable trials with vasodilating drugs. Although noncardiac adverse effects were frequent, they were not the primary reason for drug failure. Long-term therapy with amrinone may accelerate progression of left ventricular dysfunction, exacerbate myocardial ischemia and provoke life-threatening ventricular tachyarrhythmias, thereby shortening survival in patients with severe chronic heart failure. Prolonged administration of inotropic drugs may achieve short-term gains at the expense of long-term detrimental effects on the myocardium.