一项儿童肥厚型心肌病队列研究：高剂量β-肾上腺素能受体拮抗剂治疗后生存率提高

A cohort study of childhood hypertrophic cardiomyopathy: improved survival following high-dose beta-adrenoceptor antagonist treatment.

作者信息

Ostman-Smith I, Wettrell G, Riesenfeld T

机构信息

Department of Pediatrics, John Radcliffe Hospital, Oxford, United Kingdom.

出版信息

J Am Coll Cardiol. 1999 Nov 15;34(6):1813-22. doi: 10.1016/s0735-1097(99)00421-0.

DOI:10.1016/s0735-1097(99)00421-0

PMID:10577575

Abstract

OBJECTIVES

The study analyzed factors, including treatment, affecting disease-related death in patients with hypertrophic cardiomyopathy (HCM) presenting in childhood.

BACKGROUND

Previous smaller studies suggest that mortality is higher in patients with HCM presenting in childhood compared with presentation in adulthood, but these studies have all originated from selected patient populations in tertiary referral centers, and reported no significant protection by treatment.

METHODS

Retrospective comparisons of mortality were done in total cohort of patients presenting to three regional centers of pediatric cardiology. There were 66 patients (25 with Noonan's syndrome) with HCM presenting at age <19 years; mean follow-up was 12.0 years.

RESULTS

Among risk factors for death were congestive heart failure (p = 0.008), large electrocardiogram voltages (Sokolow-Lyon index p = 0.0003), and degree of septal (p = 0.004) and left ventricular (p = 0.028) hypertrophy expressed as percent of 95th centile value. The only treatment that significantly reduced the risk of death on multifactorial analysis of variance was high-dose beta-adrenoceptor antagonist therapy (propranolol 5 to 23 mg/kg/day or equivalent; p = 0.0001). Nineteen out of 40 patients managed conventionally (no treatment, 0.8 to 4 mg/kg of propranolol, or verapamil) died, median survival 15.8 years, with no deaths among 26 patients on high-dose beta-blockers (p = 0.0004); survival proportions at 10 years were 0.65 (95% confidence interval 0.49-0.80) and 1.0, respectively (p = 0.0015). Survival time analysis shows better survival in the high-dose beta-blocker group compared with the "no specific therapy" group (p = 0.0009) and with the conventional-dose beta-blocker group (p = 0.002). Hazard ratio analysis suggests that high-dose beta-blocker therapy produces a 5-10-fold reduction in the risk of disease-related death.

CONCLUSIONS

High-dose beta-blocker therapy improves survival in childhood HCM.

摘要

目的

本研究分析了包括治疗在内的影响儿童期肥厚型心肌病（HCM）患者疾病相关死亡的因素。

背景

先前规模较小的研究表明，与成年期发病的HCM患者相比，儿童期发病的患者死亡率更高，但这些研究均来自三级转诊中心的特定患者群体，且未报告治疗有显著的保护作用。

方法

对三个地区儿科心脏病中心就诊的患者总队列进行死亡率的回顾性比较。有66例年龄<19岁的HCM患者（25例患有努南综合征）；平均随访时间为12.0年。

结果

死亡的危险因素包括充血性心力衰竭（p = 0.008）、心电图高电压（索科洛夫-莱昂指数p = 0.0003）以及以第95百分位数表示的室间隔肥厚程度（p = 0.004）和左心室肥厚程度（p = 0.028）。在多因素方差分析中，唯一能显著降低死亡风险的治疗方法是高剂量β-肾上腺素能受体拮抗剂治疗（普萘洛尔5至23 mg/kg/天或等效药物；p = 0.0001）。40例接受传统治疗（未治疗、0.8至4 mg/kg普萘洛尔或维拉帕米）的患者中有19例死亡，中位生存期为15.8年，26例接受高剂量β受体阻滞剂治疗的患者无死亡（p = 0.0004）；10年时的生存比例分别为0.65（95%置信区间0.49 - 0.80）和1.0（p = 0.0015）。生存时间分析显示，高剂量β受体阻滞剂组的生存率优于“无特定治疗”组（p = 0.0009）和传统剂量β受体阻滞剂组（p = 0.002）。风险比分析表明，高剂量β受体阻滞剂治疗可使疾病相关死亡风险降低5至10倍。