肥厚型梗阻性心肌病的治疗进展

    Recent advances in the therapy of hypertrophic obstructive cardiomyopathy

    • 摘要: 肥厚型梗阻性心肌病(HOCM) 是表型多样的常染色体显性遗传性疾病。心室肌的非对称性肥厚、收缩期二尖瓣前移和左心室流出道(LVOT)的梗阻是其突出的病理生理学特征。β受体阻滞剂、非二氢吡啶类钙通道阻滞剂和丙吡胺可有效地减低LVOT梗阻,但仍有超过50%的HOCM患者对上述药物无治疗反应;心肌肌球蛋白抑制剂玛伐凯泰(Mavacamten) 和阿夫凯泰(Aficamten),已分别被数个2、3期临床试验证实对LVOT压差 ≥ 30 mmHg甚至 ≥ 50 mmHg、纽约心脏病协会心功能分级II~III级的患者治疗有效,其可逆转血流动力学障碍、改善临床症状和心功能情况;对于药物治疗无效的HOCM患者,实施室间隔减容术(SRT)可有效降低LVOT的梗阻,显著改善临床症状和预后。然而,SRT的技术壁垒和较严重的术后并发症限制了它的全面推广;近年来,中国学者刘丽文团队率先开展的经皮心肌内室间隔射频消融术可明显降低HOCM患者的LVOT梗阻,且相较于传统的SRT术,其微创的特性和较低的术后并发症更具有推广前景。

       

      Abstract: Hypertrophic obstructive cardiomyocpathy (HOCM) is phenotypically heterogeneous autosomal dominant disease with variant penetrance. Its pathophysiology primarily involves asymmetric ventricular hypertrophy, anterior motion of the systolic mitral valve, and left ventricular outflow tract (LVOT) obstruction, manifested with angina pectoris, fatigue, dyspnea, syncope, heart failure and even sudden cardiac death. Over 50% of the large patient population is drug-refractory, although traditional medications such as β-blockers, non-dihydropyridine calcium antagonists and disopyramide are selectively effective in reducing LVOT obstruction. Thus, these patients should be referred for effective septal reduction therapy, such as surgical septal myectomy or alcohol septal ablation (ASA), which is the main invasive treatment for LVOT obstruction. Recently, mavacamten and aficamten, two novel cardiac myosin inhibitors, have been proven remarkably effective in HOCM patients with LVOT gradient ≥ 30 mmHg, and even ≥ 50 mmHg, who are in New York Heart Association functional class II to III, as demonstrated by several phase 2 to 3 trials. Furthermore, percutaneous intramyocardial septal radiofrequency ablation (PIMSRA), pioneered by Liu Liwen and her colleagues, is a promising procedure because of its minimal invasiveness and comparable outcomes in decreasing LVOT obstruction compared to surgical myectomy or ASA.

       

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