CHICAGO (EGMN) – For the first time, cardiac resynchronization therapy has been shown to offer a survival benefit beyond that provided by an implantable cardioverter defibrillator in patients with mild heart failure, a study has shown.

The addition of cardiac resynchronization therapy (CRT) to an implantable cardioverter defibrillator (ICD) and optimal medical therapy significantly reduced the rates of death and heart failure hospitalization from 40% with an ICD alone to 33% in the multicenter Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT).

The relative risk of death was reduced by 25% among patients who received CRT plus ICD, resulting in an absolute mortality reduction of 6% at 5 years, Dr. Anthony Tang reported at the annual scientific sessions of the American Heart Association. Fourteen patients would need to be treated with CRT plus ICD for 5 years to prevent one death.

Significantly fewer CRT-ICD patients were hospitalized for heart failure (19.5%, or 174/894) than ICD-only patients (26%, or 236/904). This meant that 11 patients would need to be treated with CRT plus ICD for 5 years to prevent one heart failure hospitalization, said Dr. Tang, professor of medicine at the University of British Columbia, Vancouver.

RAFT enrolled 1,798 patients (mean age, 66 years), who had New York Heart Association class II or III heart failure, a left ventricular ejection fraction (LVEF) of 30% or less, and a wide QRS duration of at least 120 milliseconds or a paced QRS duration of at least 200 milliseconds. Of note, 80% of patients were NYHA class II because during the trial the protocol was changed to include only class II patients.

CRT with or without an ICD is currently indicated only for the treatment of patients with NYHA functional class III or ambulatory class IV heart failure.

The data are likely to change clinical practice, said invited discussant Dr. Clyde W. Yancy, medical director of Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallas and immediate past president of the AHA.

He observed that a suite of randomized trials including COMPANION, CARE-HF, MADIT-CRT, REVERSE, and now RAFT demonstrate compellingly that CRT is effective in heart failure.

“The benefit can now be extended to patients that have mild heart failure,” he said.

In the pivotal Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT), however, the use of CRT-ICD therapy decreased the risk of heart failure events, but not the risk of death among NYHA class I or II patients with an ejection fraction of 30% or less and a QRS duration of 130 milliseconds or more (N. Engl. J. Med. 2009; 361:1329-38).

Dr. Yancy observed that CRT plus ICD is used in only about one-third of heart failure patients and suggested that its limited uptake is due to persistent equipoise, postprocedural risks that are not insignificant, an early failure rate of about 5% and a late failure rate of up to 25%, imprecise markers of clinical response, and current guidelines.

“We should no longer let equipoise enter into our thought process about the benefits of ICD-CRT in heart failure,” he said.

The improved outcomes, however, did come at the cost of increased adverse events. Within 30 days of device implantation, significantly more CRT-ICD patients than ICD-alone patients had lead dislodgement (61 vs. 20 patients) and coronary sinus dissection (11 vs. 0), Dr. Tang reported. The CRT-ICD and ICD-alone groups had similar rates of hemothorax or pneumothorax (11 vs. 8 patients), pocket hematoma (14 vs. 11), pocket infection (21 vs. 16), tamponade (1 vs. 2), and device pocket revision (4 vs. 1).

An analysis by NYHA class showed that the majority of positive results held true, Dr. Tang said. The primary composite end point was significantly improved in both NYHA class II and III patients, while death from any cause was significantly improved among class II, but not class III patients.

Also, a post-hoc subgroup analysis of the primary end point suggests that patients with an intrinsic QRS duration of more than 150 milliseconds derive more benefit from CRT-ICD therapy, as do those with left bundle branch block, although the latter finding was weaker, Dr. Tang said. There was a trend for women to fare better with CRT plus ICD, but it was not significant.

Dr. Yancy said the observations raise intriguing considerations, but are prone to the pitfalls of post-hoc analyses, and do not indicate how to refine the rate of success and minimize morbidity.

During a panel discussion of RAFT, session moderator Dr. Marc Alan Pfeffer, the Victor J. Dzau Professor of Medicine at Brigham and Women’s Hospital in Boston, said further trials in this population are unlikely and asked whether current data are enough to suggest the use of CRT plus ICD in patients with left bundle branch block.

Dr. Yancy, who took part in the U.S. Food and Drug Administration review of the MADIT-CRT trial, responded that there was a compelling signal in MADIT-CRT for the use of CRT plus ICD among patients with left bundle branch block.

“There was nearly an 85% greater efficacy when CRT was applied to that population, and now we see the signal again,” he said. “If we are not to have further studies, I think we have to revisit both the prolongation of QRS and left block bundle pattern and understand that there may in fact be a greater likelihood of benefit with those two substrates.”

The invited discussant, Dr. Eugene Braunwald, Distinguished Hersey Professor of Medicine at Harvard Medical School in Boston, observed that the use of CRT is moving further down in less sick patients as long as they have QRS prolongation. “Where do you think this is going? ... Are you thinking of patients with [NYHA] class I or II, with better ejection fractions?” he asked.

Dr. Tang responded that clinicians need to treat patients earlier in the disease process to prevent problems, but that it remains to be seen whether CRT-ICD therapy, like beta-blockade, can be used early on.

The RAFT data were simultaneously published online by the New England Journal of Medicine (2010;10.1056/NEJM0a1009540).

RAFT was funded by the Canadian Institutes of Health Research and Medtronic of Canada. Dr. Tang disclosed research support from Boston Scientific, Medtronic, and St. Jude Medical. Dr. Yancy reported having no financial conflicts of interest.

Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

芝加哥(EGMN)——温哥华不列颠哥伦比亚大学医学教授Anthony Tang博士在美国心脏协会科学年会上报告称，心脏再同步治疗(CRT)可显著降低接受植入式心率转复除颤器(ICD)治疗的轻度心衰患者的死亡率和住院率。

 

此前研究显示CRT是一种治疗心衰的有效措施，但目前CRT加ICD或单纯CRT仅用于纽约心脏协会心脏功能III级或非卧床IV级心衰患者。此次Tang博士报告的多中心非卧床心衰患者再同步/除颤治疗试验(RAFT)，旨在观察CRT 对接受ICD治疗和最佳药物治疗的轻度患者的受益情况。RAFT纳入1,798例患者(平均年龄66岁)，他们属于纽约心脏协会II或III级心衰(其中80%为II级)，左心室射血分数(LVEF)≤30%且宽QRS时限≥120ms或起搏QRS时限≥200ms。

 

结果显示，CRT加ICD治疗可使患者死亡及心衰住院率由单纯ICD治疗的40%降至33%。患者相对死亡风险下降25%，5年绝对死亡率下降5%。因心衰住院的CRT-ICD患者(19.5%, 174/894)显著少于单纯ICD患者(26%, 236/904)。患者分级分析显示，II级和III级患者主要复合终点均得到显著改善，II级但非III级患者各种原因死亡率也有显著改善。对主要终点事后亚组分析表明，自身QRS时限> 150ms患者在CRT-ICD治疗中受益更多，左束支传导阻滞患者也从中有所受益。女性似乎对CRT-ICD 治疗效果更佳，但无统计学意义。但同时观察到，与单纯ICD相比，在植入30天内有更多的CRT-ICD患者出现电极移位(61 对20)和冠状静脉窦夹层(11对0)。两组患者发生血胸或气胸(11对8)、囊袋血肿(14对11)、囊袋感染(21对16)、心包填塞感染(1对2)以及起搏器囊袋修复(4对1)的情况类似。

 

研究表明， CRT-ICD治疗可使轻度心衰患者受益。但有学者对轻度患者是否接受CRT-ICD治疗存有异议。

 

RAFT由加拿大卫生研究所和美敦力加拿大公司资助。研究者披露获得多家医疗器械商的研究资助。

 

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