心脏再同步治疗前后循环生物标志物的特征及其在预测CRT反应中的作用：COVERT-HF研究
Characterisation of circulating biomarkers before and after cardiac resynchronisation therapy and their role in predicting CRT response: the COVERT-HF study.
作者信息
McAloon Christopher J, Barwari Temo, Hu Jimiao, Hamborg Thomas, Nevill Alan, Hyndman Samantha, Ansell Valerie, Musa Anntoniette, Jones Julie, Goodby Julie, Banerjee Prithwish, O'Hare Paul, Mayr Manuel, Randeva Harpal, Osman Faizel
机构信息
Department of Cardiology, University Hospital Coventry and Warwickshire NHS Trust, Coventry, UK.
Warwick Medical School, University of Warwick, Coventry, UK.
出版信息
Open Heart. 2018 Oct 18;5(2):e000899. doi: 10.1136/openhrt-2018-000899. eCollection 2018.
AIMS
Cardiac resynchronisation therapy (CRT) is effective treatment for selected patients with heart failure (HF) but has ~30% non-response rate. We evaluated whether specific biomarkers can predict outcome.
METHODS
A prospective single-centre pilot study of consecutive unselected patients undergoing CRT for HF between November 2013 and December 2015 evaluating cardiac extracellular matrix biomarkers and micro-ribonucleic acid (miRNA) expression before and after CRT assessing ability to predict functional response and survival. Each underwent three assessments (pre-implant, 6 weeks and 6 months postimplant) including: New York Heart Association (NYHA) class, echocardiography, electrocardiography, 6 min walk test (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHFQ) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP). Plasma markers of cardiac fibrosis assessed were: N-terminal pro-peptides of collagen I and III, collagen I C-terminal telopeptides (CTx) and matrix metalloproteinases (MMP-2 and MMP-9) as well as a panel of miRNAs (miRNA-21, miRNA-30d, miRNA-122, miRNA-133a, miRNA-210 and miRNA-486).
RESULTS
A total of 52 patients were recruited; mean age (±SD) was 72.4±9.4 years; male=43 (82.7%), ischaemic aetiology=30 (57.7%), mean QRS duration=166.4±23.5 ms, left bundle branch block (LBBB) morphology = 39 (75.0%), mean NYHA=2.7±0.6, 6MWT=238.8±130.6 m, MLHFQ=46.4±21.3 and left ventricular ejection fraction (LVEF)=24.3%±8.0%. Mean follow-up=1.7±0.3 and 5.8±0.7 months. There were 27 (55.1%) functional responders (3 no definable 6-month response; 2 missed assessments and 1 long-term lead displacement). No marker predicted response, however, CTx and LBBB trended most towards predicting functional response.
CONCLUSION
No specific biomarkers reached significance for predicting functional response to CRT. CTx showed a trend towards predicting response and warrants further study.
TRIAL REGISTRATION NUMBER
NCT02541773.
目的
心脏再同步治疗（CRT）是治疗特定心力衰竭（HF）患者的有效方法，但有~30%的无反应率。我们评估了特定生物标志物是否能预测治疗结果。
方法
一项前瞻性单中心试点研究，纳入了2013年11月至2015年12月期间连续入选的接受CRT治疗HF的患者，评估CRT前后心脏细胞外基质生物标志物和微小核糖核酸（miRNA）表达，以评估预测功能反应和生存的能力。每位患者接受三次评估（植入前、植入后6周和6个月），包括：纽约心脏协会（NYHA）分级、超声心动图、心电图、6分钟步行试验（6MWT）、明尼苏达心力衰竭生活问卷（MLHFQ）和N末端脑钠肽前体（NT-pro-BNP）。评估的心脏纤维化血浆标志物包括：I型和III型胶原的N末端前肽、I型胶原C末端肽（CTx）和基质金属蛋白酶（MMP-2和MMP-9）以及一组miRNA（miRNA-21、miRNA-30d、miRNA-122、miRNA-133a、miRNA-210和miRNA-486）。
结果
共招募了52例患者；平均年龄（±标准差）为72.4±9.4岁；男性43例（82.7%），缺血性病因30例（57.7%），平均QRS时限=166.4±23.5毫秒，左束支传导阻滞（LBBB）形态39例（75.0%），平均NYHA=2.7±0.6，6MWT=238.8±130.6米，MLHFQ=46.4±21.3，左心室射血分数（LVEF）=24.3%±8.0%。平均随访时间=1.7±0.3和5.8±0.7个月。有27例（55.1%）功能反应者（3例在6个月时无明确反应；2例错过评估，1例长期导线移位）。没有标志物能预测反应，然而，CTx和LBBB在预测功能反应方面最具趋势性。
结论
没有特定的生物标志物在预测CRT功能反应方面达到显著水平。CTx显示出预测反应的趋势，值得进一步研究。
试验注册号
NCT02541773。
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