PFO增加ICD和起搏器植入者的卒中风险

洛杉矶——一项对美国梅奥医院6,000多例患者的回顾性分析表明，安装了置入式心脏复律除颤器(ICD)或心脏起搏器的卵圆孔未闭(PFO)患者，可能最适合接受其心脏缺陷的靶向修补治疗。


Christopher V. DeSimone博士
 
美国罗切斯特梅奥医院的内科医生Christopher V. DeSimone博士及其同事对6,086例于2000年1月~2010年10月期间在该院安装了ICD或永久性起搏器的患者进行了回顾性分析，其中包括375例PFO患者。患者的平均年龄为67岁；男性几乎占到了2/3。大约15%有卒中或短暂性脑缺血发作(TIA)病史，约44%患有房颤，平均CHA2D2-VASc评分为3.1分。

在4.7年的平均随访期内，PFO患者的卒中或TIA发生率为11%，而非PFO患者的发生率仅为2%。针对基线人口统计学和临床差异(包括房颤以及阿司匹林和华法林的使用情况)进行校正后的多因素分析显示，PFO患者发生卒中或TIA的风险比非PFO患者高4.6倍，差异有统计学意义。

其他分析还显示，无论患者是否接受了阿司匹林或华法林的治疗，无论患者是否年龄超过65岁或者是否有卒中或TIA病史，也无论患者CHA2D2-VASc评分的高低，卒中和TIA的发生率在PFO患者中都显著增加。

与PFO和卒中或TIA之间显著的相关性不同，研究者发现PFO与全因死亡率之间无明显的相关性。

卒中和TIA发生率上的PFO相关差异首次在ICD或起搏器植入后1年左右达到了统计学显著性水平。然后，事件曲线继续分离，随着时间的推移越分越开。DeSimone博士推测道，源于植入装置的微栓子可能穿过PFO进入肺循环，从而导致了植入后1年内肺动脉压力增加。然后，右侧高压形成了右向左分流，导致栓塞风险增加。

DeSimone博士总结道：“我们认为这是一个高危人群，PFO修补术对于这类患者应该有益。”他承认多项近期开展的随机试验表明PFO修补术对于卒中预防的效果较差，但他同时也指出安装了ICD或永久性起搏器的PFO患者可能是一个特殊的亚组，这组患者应该会受益于PFO修补术。

DeSimone博士在接受采访时说：“如果患者的右侧心房或心室置入了电极，血块在PFO周围形成并停留，那么患者发生卒中或TIA 的风险就会很高。”事实上，那些评估PFO修补术疗效的试验都明确排除了安装了永久性起搏器的患者，也排除了许多ICD植入者，因为这类患者的左室功能明显受损，CLOSURE I试验就是如此(N. Engl. J. Med. 2012;366:991-99)。

他补充道，由于这项研究采用的是回顾性分析，可能存在一些未经校正的混杂因素，所以有一定的局限性，“还需开展更多的前瞻性研究”。此外，鉴于就许多病例而言，用于检测PFO和卒中的方法并非是最佳方法，因此该分析中的卒中风险可能还低估了PFO加心脏装置所带来的实际风险。

DeSimone博士声明无相关利益冲突。

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By: MITCHEL L. ZOLER, Cardiology News Digital Network

LOS ANGELES – Patients with a patent foramen ovale and an implanted defibrillator or pacemaker may be perfect candidates for targeted closure of their heart defect, based on a review of more than 6,000 patients who received a device at one U.S. center.

During an average follow-up of nearly 5 years, patients with a patent foramen ovale (PFO) who received an implantable cardioverter defibrillator (ICD) or a permanent pacemaker were more than fourfold more likely to develop a stroke or transient ischemic attack (TIA) compared with implanted device recipients who did not have a PFO, Dr. Christopher V. DeSimone said at the meeting.

"We think that this is a high-risk population that might benefit from PFO closure," said Dr. DeSimone, an internal medicine physician at the Mayo Clinic in Rochester, Minn. He acknowledged the poor efficacy of PFO closure for stroke prevention in several recent randomized trials, but noted that patients with a PFO who receive an ICD or permanent pacemaker may constitute a special subgroup that stands to benefit from PFO closure.

"If a patient has a right atrial or ventricular lead and a clot forms and sits there next to the PFO they would be at high risk" for a stroke or TIA, he said in an interview. In fact, trials that have assessed the efficacy of PFO closure explicitly excluded patients with permanent pacemakers as well as many ICD recipients because of their substantially impaired left ventricular function, such as in the CLOSURE I trial (N. Engl. J. Med. 2012;366:991-99). "This needs to be studied prospectively," he added, noting that his study was limited by being retrospective and potentially subject to unadjusted confounding.

Dr. DeSimone and his associates reviewed 6,086 patients who received an ICD or permanent pacemaker at the Mayo Clinic during January 2000 to October 2010. The group included 375 patients with PFOs. Average age of the patients was 67 years; nearly two-thirds were men. About 15% had a history of stroke or TIA, about 44% had atrial fibrillation, and their average CHA2D2-VASc score was 3.1.

During an average follow-up of 4.7 years, the incidence of stroke or TIA was 11% in the PFO patients and 2% in the patients without a PFO. In a multivariate analysis that controlled for baseline demographic and clinical differences, including atrial fibrillation and aspirin and warfarin use, patients with a PFO were 4.6-fold more likely to have a stroke or TIA than were patients without a PFO, a statistically significant difference.

Additional analyses showed that the stroke and TIA rate remained significantly elevated in the PFO patients regardless of whether patients were on treatment with aspirin or on warfarin, and also regardless of whether or not they were older than age 65 or had a history of stroke or TIA, and regardless of whether they had a low or high CHA2D2-VASc score, Dr. DeSimone said.

In contrast to the strong, consistent link between PFOs and stroke or TIA, the researchers saw no significant link between the presence of a PFO and all-cause mortality.

The PFO-related difference in the incidence of stroke and TIA first became apparent about 1 year after device placement. The event curves then continued to diverge more and more over time. He hypothesized that micro-emboli that originate on the device leads pass through the PFO and into the pulmonary circulation, causing increased pulmonary-artery pressures during the year after device placement. The increased right-sided pressure then favors a right-to-left shunt and increased embolization.

Also, the stroke risk in this analysis may have underestimated the true risk posed by the combination of a PFO and a heart device because the methods used to detect PFOs and stroke may not have been optimal in many cases.

Dr. Desimone said that he had no disclosures.