专家视点：为何心脏再同步治疗对女性效果更佳

迈阿密海滩——在国际黑人高血压学会2012年会上，来自美国FDA医疗器械与放射健康中心的医疗官David G. Strauss博士称，心衰女性患者对心脏再同步治疗(CRT)的反应优于男性患者，但长期以来没人知道其原因何在。


David G. Strauss博士

在MADIT-CRT(多中心自动除颤器植入试验——心脏再同步治疗)中，1,820例患者被随机分组，接受埋藏式心脏复律除颤器(ICD) 加CRT治疗或者单纯ICD治疗。结果显示，对于QRS间期介于130~140 ms的男性患者，CRT无效，反而出现了与器械相关的伤害趋势[危险比(HR)，1.69]。相比之下，对于QRS间期介于130~140 ms的女性患者，CRT的治疗效果却非常好(HR，0.20)，心衰住院或死亡率下降了80%。

Strauss博士指出，在女性患者中非缺血性心肌病的发生率更高，这意味着心肌瘢痕更少，因而对CRT的反应更好。无论采用哪种电刺激方式，心肌瘢痕都不会收缩。

此外，MADIT-CRT试验还表明，合并左束支传导阻滞的患者接受CRT治疗可能会显著降低其心衰住院率和死亡率。相反，对于不存在左束支传导阻滞的患者，CRT治疗无临床优势。

不过，Strauss博士提醒道，应谨慎识别左束支传导阻滞。研究表明，通过常规心电图标准诊断的左束支传导阻滞病例中大约有1/3都是误诊(Am. J. Cardiol. 2011;107:927-34)。存在室内传导延迟的患者同样也可能表现出QRS间期延长，比如因左室肥大和左室扩张致室内传导延迟的患者其QRS间期可能处于左束支传导阻滞的诊断范围之内，但其实这类患者并不存在左束支传导阻滞。

Strauss博士称：“近期几个专业学术团体都建议将CRT用于QRS间期≥150 ms的患者，且目标人群以2级心衰患者为主。”然而，这一阈值“会把合并左束支传导阻滞和QRS间期介于130~149 ms 的女性患者排除在外，而这类患者在MADIT-CRT 试验中接受CRT治疗后效果很好”(Circulation 2011;123:1061-72)。

Strauss博士指出，制定新标准将有助于选择更合适的患者来接受CRT治疗。“现已证实CRT能够改善心衰症状，降低心衰住院率和死亡率。但并非所有心衰患者都能从CRT治疗中获益，CRT同样也存在很大的风险。”例如，与单纯ICD治疗相比，再多植入1个带有左室电极的CRT装置可能会引发更多的并发症。“因此，我们有必要完善相关的患者风险分层体系和患者识别标准。”

基于电刺激描记和模拟研究的结果，Strauss博士及其同事“提出了更为严格的左束支传导阻滞诊断标准”。例如，他们将诊断左束支传导阻滞的QRS间期阈值从过去的男女均为120 ms改为女性QRS间期≥130 ms，男性≥140 ms。

Strauss博士及其同事提出的另一条新诊断标准是在I、aVL、V1、V2、V5或V6心电图导联中至少有2个导联出现了QRS中段切迹。这对于诊断左束支传导阻滞非常重要，因其反映了两点：其一当电刺激到达左室心内膜时出现了第一个切迹，其二当电刺激到达室间隔对面的外侧壁时出现了第二个切迹。

其他研究者也支持更改现有的左束支传导阻滞诊断标准。在一项纳入了111例患者的研究中，研究者发现与新的严格标准相比，采用所谓的“假”标准与心衰住院率或死亡率增加4倍相关(Pacing Clin. Electrophysiol. 2012;35:927-34)。

CRT经FDA批准可以用于缺血性或非缺血性3级或4级心衰且左室射血分数<35%、QRS间期>120 ms的患者。FDA还批准CRT用于1级缺血性或2级(缺血性或非缺血性)心衰合并左束支传导阻滞且左室射血分数<30%、QRS间期>130 ms的患者。

Strauss声明无相关经济利益冲突。

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By: DAMIAN MCNAMARA, Cardiology News Digital Network

MIAMI BEACH – When it comes to heart failure, women tend to respond better to cardiac resynchronization therapy than do men, but for a long time no one knew why.

Turns out women have some distinct physiologic advantages, specifically more left bundle branch block and more nonischemic cardiomyopathy. Each drives a better response to cardiac resynchronization therapy (CRT), said Dr. David G. Strauss, a medical officer at the Food and Drug Administration’s Center for Devices and Radiologic Health in Silver Spring, Md.

In addition, timing of a specific electrical component within the heart triggers a third important distinction. Women benefit significantly from CRT even when their QRS duration is shorter than 150 msec. This supports the need for new gender-specific criteria for left bundle branch block and, ultimately, better identification of patients most likely to benefit from CRT device placement, Dr. Strauss said at the annual meeting of the International Society on Hypertension in Blacks.

"This is important because different professional societies recently have recommended that CRT be given to patients with QRS duration of 150 msec or more, and primarily in class II heart failure," he said. However, this cutoff "would exclude women with left bundle branch block and QRS duration 130-149 msec that derived significant benefit in MADIT-CRT" (Circulation 2011;123:1061-72).

In MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy), 1,820 patients were randomly assigned to receive CRT with an implantable cardioverter-defibrillator (ICD) or an ICD alone. In men with QRS duration of 130-140 msec in the study, there was no benefit from CRT and a trend toward harm associated with the device (hazard ratio, 1.69), Dr. Strauss said.

In contrast, women with QRS durations of 130-140 msec "had very significant benefit from CRT with a hazard ratio of 0.20, indicating 80% decrease in heart failure hospitalization or death," Dr. Strauss said.

More nonischemic cardiomyopathy among women translates to less myocardial scar and, ultimately, to a better CRT response. Scar tissue, no matter how it is electrically activated, does not contract, Dr. Strauss said.

Presence of left bundle branch block conferred a significant benefit in terms of reduced heart failure hospitalizations and deaths with use of CRT in the MADIT-CRT research. Conversely, participants without left bundle branch block realized no clinical advantage with CRT.

Be careful, however, to correctly identify left bundle branch block, Dr. Strauss said. Research suggests that one third of patients diagnosed with left bundle branch block by conventional electrocardiographic criteria are misdiagnosed (Am. J. Cardiol. 2011;107:927-34). Patients with intraventricular conduction delays, such as those caused by left ventricular hypertrophy and left ventricular dilation who do not have a blocked left bundle branch, can still display a prolonged QRS duration. This duration can be in the range generally considered diagnostic of left bundle branch block.

New criteria could parlay into better patient selection in the future, Dr. Strauss said. "CRT has been shown to improve heart failure symptoms, reduce heart failure hospitalization, and reduce mortality. However, not all patients benefit and significant risks exist." For example, addition of a CRT device with a left ventricular lead is associated with more complications, compared with ICD alone. "Thus there is a need for better patient risk stratification and patient identification criteria."

Based on results of electrical activation mapping and simulation studies, "My colleagues and I proposed stricter left bundle branch block criteria," he said. For example, they propose QRS duration of 130 msec or greater in women and 140 msec greater in men to replace the conventional 120 msec definition of left bundle branch block in either gender.

Another proposed new requirement is mid-QRS notching in at least two of the electrocardiographic leads of I, aVL, V1, V2, V5, or V6. This is important for diagnosing left bundle branch block because it reflects two events, Dr. Strauss said. There is an initial notch when electrical activation reaches the endocardium of the left ventricle and a second notch when activation reaches the lateral wall opposite the septum.

Other researchers support changing the current criteria for left bundle branch block. In a study of 111 patients, researchers found meeting what they termed "false" criteria was associated with a fourfold higher rate of heart failure hospitalization or death, compared with those meeting strict criteria (Pacing Clin. Electrophysiol. 2012;35:927-34).

CRT is FDA approved for class 3 or 4 heart failure, both of ischemic and nonischemic etiology, with a left ventricular ejection fraction less than 35% and a QRS duration over 120 msec. The FDA also approved CRT for class I ischemic or class II (ischemic or nonischemic) heart failure with an ejection fraction less than 30%, a QRS duration over 130 msec, and left bundle branch block.

Dr. Strauss reported no relevant financial disclosures.