Department of Molecular and Clinical Cardiology, Institute of Medicine, Sahlgrenska Akademy at the University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
Cardiac Department, Uddevalla Hospital, Uddevalla, Sweden.
Open Heart. 2019 Jun 27;6(1):e000963. doi: 10.1136/openhrt-2018-000963. eCollection 2019.
In order to avoid effects of referral bias, we assessed risk factors for disease-related mortality in a geographical cohort of patients with hypertrophic obstructive cardiomyopathy (HOCM), and any therapy effect on survival.
Diagnostic databases in 10 hospitals in the West Götaland Region yielded 251 adult patients with HOCM (128 male, 123 female). Case notes were reviewed for clinical data and ECG and ultrasound findings. Beta-blockers were used in 71.3% of patients from diagnosis (median metoprolol-equivalent dose of 125 mg/day), and at latest follow-up in 86.1%; 121 patients had medical therapy alone, 88 short atrioventricular delay pacing and 42 surgical myectomy. Mean follow-up was 14.4±8.9 (mean±SD) years. Primary endpoint was disease-related death, and secondary endpoint heart failure deaths.
There were 65 primary endpoint events. Independent risk factors for disease-related death on multivariate Cox hazard regression were: female sex (p=0.005), age at diagnosis (p<0.001), outflow gradient ≥50 mm Hg at diagnosis (p=0.036) and at follow-up (p=0.001). Heart failure caused 62% of deaths, and sudden cardiac death 17%. Late independent predictors of heart failure death were: female sex (p=0.003), outflow gradient ≥50 mm Hg at latest follow-up (p=0.032), verapamil/diltiazem therapy (p=0.012) and coexisting hypertension (p=0.031), but not other comorbidities. Neither myectomy nor pacing modified survival, but early and maintained beta-blocker therapy was associated with dose-dependent reduction in disease-related mortality in the multivariate model (p=0.028), and final dose was also associated with reduced heart failure mortality (p=0.008). Kaplan-Meier survival curves analysed in initial dose bands of 0-74, 75-149 and ≥150 mg metoprolol/day showed 10-year freedom from disease-related deaths of 83.1%, 90.7% and 97.0%, respectively (p=0.00008). Even after successful relief of outflow obstruction by intervention, there was survival benefit of metoprolol doses ≥100 mg/day (p=0.01).
In population-based HOCM cohorts heart failure is a dominant cause of death and on multivariate analysis beta-blocker therapy was associated with a dose-dependent cardioprotective effect on total, disease-related as well as heart failure-related mortality.
为了避免转诊偏倚的影响，我们评估了肥厚型梗阻性心肌病（HOCM）患者地理队列中与疾病相关的死亡率的危险因素，以及任何治疗对生存的影响。
在西约塔兰地区的 10 家医院的诊断数据库中，纳入了 251 名成年 HOCM 患者（男性 128 名，女性 123 名）。对病历进行了临床数据、心电图和超声检查结果的审查。β受体阻滞剂在诊断时（美托洛尔等效剂量中位数为 125mg/天）用于 71.3%的患者，在最近的随访中用于 86.1%的患者；121 名患者仅接受药物治疗，88 名患者接受短房室延迟起搏，42 名患者接受手术心肌切除术。平均随访时间为 14.4±8.9（平均值±标准差）年。主要终点是与疾病相关的死亡，次要终点是心力衰竭死亡。
共有 65 例主要终点事件。多变量 Cox 风险回归分析中与疾病相关死亡的独立危险因素为：女性（p=0.005）、诊断时年龄（p<0.001）、诊断时（p=0.036）和随访时（p=0.001）的流出道梯度≥50mmHg。心力衰竭导致 62%的死亡，心脏性猝死导致 17%的死亡。心力衰竭死亡的晚期独立预测因素为：女性（p=0.003）、最新随访时流出道梯度≥50mmHg（p=0.032）、维拉帕米/地尔硫䓬治疗（p=0.012）和合并高血压（p=0.031），但不包括其他合并症。心肌切除术或起搏均未改变生存率，但早期和持续的β受体阻滞剂治疗与多变量模型中与疾病相关的死亡率呈剂量依赖性降低相关（p=0.028），最终剂量也与心力衰竭死亡率降低相关（p=0.008）。按初始美托洛尔剂量分为 0-74、75-149 和≥150mg 三个剂量组进行 Kaplan-Meier 生存曲线分析，结果显示 10 年无疾病相关死亡率分别为 83.1%、90.7%和 97.0%（p=0.00008）。即使流出道梗阻经介入治疗成功缓解后，美托洛尔剂量≥100mg/天也能带来生存获益（p=0.01）。
在基于人群的 HOCM 队列中，心力衰竭是主要死亡原因，多变量分析显示β受体阻滞剂治疗与总死亡率、与疾病相关的死亡率以及与心力衰竭相关的死亡率呈剂量依赖性的心脏保护作用相关。
