Beta-Blocker (Bisoprolol) vs Calcium-Channel Blocker (Verapamil) in Nonobstructive Hypertrophic Cardiomyopathy: A Randomized Triple-Crossover Physiologic Trial.

The authors sought to analyze the effect of bisoprolol and verapamil treatment in nonobstructive HCM in a randomized, double-blinded, placebo-controlledtriple-crossover trial.

作者试图通过一项随机、双盲、安慰剂对照的三交叉试验来分析比索洛尔和维拉帕米在非梗阻性HCM中的治疗效果。

Methods

Nonobstructive HCM patients with ≥1 marker of disease severity (NYHA functional class ≥II, N-terminal pro-B-type natriuretic peptide [NT-proBNP] >300 ng/L, or documented nonsustained ventricular tachycardia) were included.

纳入了具有≥1个疾病严重性标志物（NYHA功能分级≥II级，N末端前体B型利钠肽[NT-proBNP] >300 ng/L，或记录到的非持续性室性心动过速）的非梗阻性肥厚型心肌病患者。

Each patient underwent 3 treatment periods with target doses of 7.5 mg bisoprolol, 360 mg verapamil, and placebo.

每位患者接受了3个治疗周期，目标剂量为7.5 mg比索洛尔，360 mg维拉帕米和安慰剂。

Outcomes were evaluated after 2 weeks on steady-state treatment.

在稳态治疗2周后评估了结果。

The primary outcome was peak oxygen consumption (pVO2).

主要结果是峰值氧耗量（pVO2）。

In addition, exercise response, symptom, biomarker, structural, and myocardial changes were evaluated.

此外，还评估了运动反应、症状、生物标志物、结构和心肌变化。

Results

Thirty-two patients (34% women) aged 54 ± 15 years were included.

共有32名患者（34%为女性）纳入研究，平均年龄为54±15岁。

The pVO2 was 25.7 ± 8.7 mL/kg/min with bisoprolol, 28.2 ± 8.6 mL/kg/min with verapamil and 28.7 ± 8.7 mL/kg/min with placebo.

使用比索洛尔时的pVO2为25.7 ± 8.7 mL/kg/min，使用维拉帕米时为28.2 ± 8.6 mL/kg/min，使用安慰剂时为28.7 ± 8.7 mL/kg/min。

The adjusted mean difference in pVO2 was -1.8 mL/kg/min (P = 0.013) bisoprolol vs verapamil, -2.5 mL/kg/min (P = 0.002) bisoprolol vs placebo and -0.7 mL/kg/min (P = 0.990) verapamil vs placebo.

调整后的平均pVO2差异为-1.8 mL/kg/min（P = 0.013）比索洛尔对比维拉帕米，-2.5 mL/kg/min（P = 0.002）比索洛尔对比安慰剂，以及-0.7 mL/kg/min（P = 0.990）维拉帕米对比安慰剂。

The peak heart rate was lower with bisoprolol (-37 beats/min; P < 0.001) and with verapamil (-17 beats/min; P < 0.001) compared with placebo.

与安慰剂相比，比索洛尔(-37次/分钟; P < 0.001)和维拉帕米(-17次/分钟; P < 0.001)使心率峰值降低。

Neither bisoprolol nor verapamil changed the oxygen consumption at anaerobic threshold or the minute ventilation/CO2 production slope.

比索洛尔和维拉帕米均未改变无氧阈值时的氧耗量或每分钟通气量/二氧化碳产生率斜率。

Global longitudinal strain was improved by verapamil (-1.1%; P = 0.001) but unchanged by bisoprolol (-0.6%; P = 0.263) compared with placebo.

与安慰剂相比，维拉帕米改善了全球纵向应变（-1.1%；P = 0.001），而比索洛尔则未见明显变化（-0.6%；P = 0.263）。

Compared with placebo, treatment with bisoprolol reduced Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS; -6.6 points; P = 0.001), increased NT-proBNP (+165 ng/L; P = 0.006), increased left atrial volume index (LAVI; +13.0 mL/m2; P < 0.001), and increased tricuspid regurgitation (TR) pressure gradient (+4.3 mm Hg; P = 0.049).

与安慰剂相比，比索洛尔治疗降低了堪萨斯城心肌病问卷总体总结评分（KCCQ-OSS；-6.6分；P = 0.001），增加了NT-proBNP（+165 ng/L；P = 0.006），增加了左房体积指数（LAVI；+13.0 mL/m2；P < 0.001），并增加了三尖瓣返流（TR）压力梯度（+4.3 mm Hg；P = 0.049）。

Treatment with verapamil did not change KCCQ-OSS (-2.3 points; P = 0.668), LAVI (+5.2 mL/m2; P = 0.194), or TR pressure gradients (+1.1 mm Hg; P = 1.000), but reduced NT-proBNP (-177 ng/L; P < 0.001) compared with placebo.

与安慰剂相比，维拉帕米治疗未改变KCCQ-OSS评分（-2.3分；P=0.668）、LAVI（+5.2 mL/m^2；P=0.194）或TR压力梯度（+1.1 mm Hg；P=1.000），但降低了NT-proBNP（-177 ng/L；P<0.001）水平。

NYHA functional classification was unchanged by treatments.

治疗并未改变纽约心脏病协会（NYHA）功能分级。

Conclusions

In nonobstructive HCM, treatment with bisoprolol reduced pVO2, whereas it was unchanged with verapamil.

在非梗阻性肥厚型心肌病中，比索洛尔治疗降低了最大摄氧量（pVO2），而维拉帕米治疗则未见改变。

There were a number of significant differences in exercise response, structural changes, myocardial function, symptoms, and biomarkers.

在运动反应、结构变化、心肌功能、症状和生物标志物方面存在许多显著差异。

This study provides new insights into the mechanisms of these drugs that might be taken into consideration in management of nonobstructive HCM.

本研究为这些药物的作用机制提供了新的见解，这些见解可能会被考虑用于非梗阻性肥厚型心肌病的管理。