Cardiovascular Research Centre, Royal Brompton Hospital & National Heart Lung Institute, Imperial College, London, UK.
London School of Hygiene and Tropical Medicine, London, UK.
Eur J Heart Fail. 2021 Feb;23(2):293-301. doi: 10.1002/ejhf.2063. Epub 2020 Dec 14.
To characterize adverse ventricular remodelling after withdrawing therapy in recovered dilated cardiomyopathy (DCM).
TRED-HF was a randomized controlled trial with a follow-on single-arm cross-over phase that examined the safety and feasibility of therapy withdrawal in patients with recovered DCM over 6 months. The primary endpoint was relapse of heart failure defined by (i) a reduction in left ventricular (LV) ejection fraction >10% and to <50%, (ii) >10% increase in LV end-diastolic volume and to above the normal range, (iii) a twofold rise in N-terminal pro-B-type natriuretic peptide and to >400 ng/L, or (iv) evidence of heart failure. LV mass, LV and right ventricular (RV) global longitudinal strain (GLS) and extracellular volume were measured using cardiovascular magnetic resonance at baseline and follow-up (6 months or relapse) for 48 patients. LV cell and extracellular matrix masses were derived. The effect of withdrawing therapy, stratified by relapse and genotype, was investigated in the randomized and follow-on phases. In the randomized comparison, withdrawing therapy led to an increase in mean LV mass [5.4 g/m ; 95% confidence interval (CI) 1.3-9.5] and cell mass (4.2 g/m ; 95% CI 0.5-8.0) and a reduction in LV (3.5; 95% CI 1.6-5.5) and RV (2.4; 95% CI 0.1-4.7) GLS. In a non-randomized comparison of all patients (n = 47) who had therapy withdrawn in either phase, there was an increase in LV mass (6.2 g/m ; 95% CI 3.6-8.9; P = 0.0001), cell mass (4.0 g/m ; 95% CI 1.8-6.2; P = 0.0007) and matrix mass (1.7 g/m ; 95% CI 0.7-2.6; P = 0.001) and a reduction in LV GLS (2.7; 95% CI 1.5-4.0; P = 0.0001). Amongst those who had therapy withdrawn and did not relapse, similar changes were observed (n = 28; LV mass: 5.1 g/m , 95% CI 1.5-8.8, P = 0.007; cell mass: 3.7 g/m , 95% CI 0.3-7.0, P = 0.03; matrix mass: 1.7 g/m , 95% CI 0.4-3.0, P = 0.02; LV GLS: 1.7, 95% CI 0.1-3.2, P = 0.04). Patients with TTN variants (n = 10) who had therapy withdrawn had a greater increase in LV matrix mass (mean effect of TTN: 2.6 g/m ; 95% CI 0.4-4.8; P = 0.02).
In TRED-HF, withdrawing therapy caused rapid remodelling, with early tissue and functional changes, even amongst patients who did not relapse.
描述撤去治疗后扩张型心肌病（DCM）患者心室重构不良的特征。
TRED-HF 是一项随机对照试验，随后进行了单臂交叉的后续阶段研究，以评估恢复性 DCM 患者撤去治疗的安全性和可行性，随访时间为 6 个月。主要终点是心力衰竭复发的定义为（i）左心室射血分数下降>10%，至<50%；（ii）左心室舒张末期容积增加>10%，至超出正常范围；（iii）N-末端脑钠肽前体升高两倍，至>400ng/L；或（iv）心力衰竭的证据。48 例患者在基线和随访（6 个月或复发）时使用心血管磁共振测量左心室质量、左心室和右心室整体纵向应变（GLS）和细胞外体积。得出左心室细胞和细胞外基质质量。在随机和后续阶段，按复发和基因型分层，研究了撤去治疗的效果。在随机比较中，撤去治疗导致左心室质量增加[5.4g/m；95%置信区间（CI）1.3-9.5]和细胞质量增加[4.2g/m；95%CI 0.5-8.0]，左心室（3.5；95%CI 1.6-5.5）和右心室（2.4；95%CI 0.1-4.7）GLS 降低。在任意阶段撤去治疗的所有患者（n=47）的非随机比较中，左心室质量增加（6.2g/m；95%CI 3.6-8.9；P=0.0001）、细胞质量增加（4.0g/m；95%CI 1.8-6.2；P=0.0007）和基质质量增加（1.7g/m；95%CI 0.7-2.6；P=0.001），左心室 GLS 降低（2.7；95%CI 1.5-4.0；P=0.0001）。在撤去治疗且未复发的患者中观察到类似的变化（n=28；左心室质量：5.1g/m，95%CI 1.5-8.8，P=0.007；细胞质量：3.7g/m，95%CI 0.3-7.0，P=0.03；基质质量：1.7g/m，95%CI 0.4-3.0，P=0.02；左心室 GLS：1.7，95%CI 0.1-3.2，P=0.04）。撤去治疗的肌联蛋白（TTN）变异患者（n=10）左心室基质质量增加更大（TTN 的平均效应：2.6g/m；95%CI 0.4-4.8；P=0.02）。
在 TRED-HF 中，撤去治疗导致了快速的重构，即使在未复发的患者中，也会出现早期的组织和功能变化。
