长期监测是隐源性卒中后房颤的最佳检测手段

《新英格兰医学杂志》6月26日发表的两项随机研究显示，在既往发生“隐源性”卒中或短暂性脑缺血发作（TIA）的患者中，长期心律监测方法的阵发性房颤（AF）检出率显著高于常规方法。

Dr. David J. Gladstone

在第1项研究中，加拿大多伦多大学神经科的David J. Gladstone医生及其同事使用非侵入性动态心电图（ECG）对572例刚发生缺血性卒中或TIA的患者（平均72岁，范围52~96岁）的心律进行了为期30天的跟踪监测。综合评估（通常包括常规24小时Holter监测）未能识别任何AF和卒中或TIA事件的其他原因，因此将卒中或TIA事件归类为隐源性。在加拿大的16个卒中中心，这些患者在3年内随机接受长期ECG监测干预（287例患者）或接受额外1轮的24小时Holter监测（285例对照者），以期检出隐匿性AF。结果显示，长期ECG监测检出AF的能力更高，该方法在16.1%的患者中检出至少1次AF发作，而对照组仅3.2%的患者被检出至少1次AF发作。长期监测检出持续2.5 min至数小时的连续性AF的能力也更高，该组此类AF的检出率为9.9%，而对照组仅为2.5%（N. Engl. J. Med. 2014 June 26 [doi:10.1056/NEJMoa1311376]）。

研究者表示，长期监测组此后使用抗凝药物进行卒中二级预防的患者比例是对照组的近2倍，研究者将这一结果视为卒中复发预防治疗方面具有临床意义的改变。研究者认为在原因未确定的卒中或TIA后常规进行24~48小时AF监测是不充分的，应将这视为初始筛查而非最终检查，因为该研究发现单纯通过临床随访作为检测AF的手段，其检出率可忽略不计。

在第2项研究中，罗马圣心天主教大学心脏病研究所的Tommaso Sanna医生及其同事在新近发生隐源性缺血性卒中或TIA的441例患者（平均61.5岁）中对常规随访与使用植入式心脏监测仪（ICM）的心律监测进行了比较。ICM可自动检测和记录AF，不管心率或症状如何。对照组患者在预定和未预定的访视时接受评估，进行ECG监测与否由研究者自行决定。

结果显示，6个月时，被随机分入研究干预组的221例患者的AF检出率为8.9%，而220例对照者中的AF检出率仅为1.4%。12个月时，两组的AF检出率分别为12.4%和2.0%。在根据年龄、性别、人种/族裔、索引事件类别、有无卵圆孔未闭和CHADS评分划分的所有亚组患者中均一致观察到这一检出率方面的差异（N. Engl. J. Med. 2014 June 26 [doi:10.1056/NEJMoa1313600]）。

如同第1项研究观察到的那样，第2项研究也观察到ICM监测组使用口服抗凝药进行二级预防的患者比例是对照组的2倍多。ICM策略的获益明显：在6个月监测期间，为了检出1次AF发作，仅需植入14个监测仪；在12个月随访期间，为了检出1次AF发作，仅需植入10个监测仪；在36个月随访期间，为了检出1次AF发作，仅需植入4个监测仪。

两项研究的结果表明，在当前实践中，大量被归类为隐源性卒中或TIA的患者实际上存在未诊断和未治疗的隐匿性AF。两项研究的研究者均表示，由于AF未被识别的卒中存活者通常使用抗血小板药进行二级预防，而抗血小板药的效果劣于用于临床显性AF的抗凝药物，因此检出隐匿性AF具有重要意义。

第1项研究获加拿大卒中网络等多家机构支持。Gladstone医生声明从拜耳等多家药企获得支持，其同事也声明与多家药企存在联系。第2项研究获研究中所用ICM的生产商美敦力公司支持。Sanna医生声明与美敦力公司存在其他联系，其同事声明与多家药企存在联系。

Dr. Hooman Kamel

随刊述评

标准治疗应该现在就作出改变

纽约康奈尔大学神经科的Hooman Kamel医生表示，这两项研究的结果表明，长期心律监测应现在就成为隐源性卒中患者的标准治疗的一部分。大部分隐源性卒中或TIA患者应接受至少数周的心律监测。相对便宜的外部循环记录仪（如第1项研究中使用的记录仪）可能具有较好的成本效益；而较贵的植入式循环记录仪的价值尚不太明确（N. Engl. J. Med. 2014 June 26 [doi:10.1056/NEJMe1405046]）。

By: MARY ANN MOON, Cardiology News Digital Network

Extended monitoring of heart rhythm detected paroxysmal atrial fibrillation in patients who had previously had a "cryptogenic" stroke or transient ischemic attack at significantly higher rates than did conventional methods in two separate, randomized studies published June 26 in the New England Journal of Medicine.

Revealing the occult atrial fibrillation (AF) is critical because stroke survivors whose AF is unrecognized typically receive antiplatelet therapy for secondary prevention, which is inferior to the anticoagulation treatment given for clinically apparent AF, both groups of researchers said.

At 16 stroke centers across Canada, these patients were randomly assigned during a 3-year period to either the prolonged ECG monitoring intervention (287 patients) or to one additional round of 24-hour Holter monitoring (285 control subjects) in the hope of detecting occult AF. The extended ECG monitoring proved superior, detecting at least one episode of AF in 16.1% of patients, compared with only 3.2% in the control group. The extended monitoring also was superior at detecting continuous AF lasting from 2.5 minutes to many hours, which was found in 9.9% of the intervention group vs. only 2.5% of the control group, the investigators reported (N. Engl. J. Med. 2014 June 26 [doi:10.1056/NEJMoa1311376]).In one study, investigators used noninvasive ambulatory ECG monitoring to track heart rhythm for 30 days in 572 patients aged 52-96 years (mean age, 72 years) soon after they had an ischemic stroke or transient ischemic attack (TIA). Comprehensive evaluations, typically including the conventional 24-hour session of Holter monitoring, failed to identify any AF or other cause of the event, so it was classified as cryptogenic, said Dr. David J. Gladstone of the division of neurology, University of Toronto, and coleader of the University of Toronto Stroke Program, and his associates.

The prolonged monitoring "nearly doubled the proportion of patients who subsequently received anticoagulant therapy for secondary prevention of stroke – a finding we interpret as a clinically meaningful change in treatment that has the potential to avert recurrent strokes," Dr. Gladstone and his associates wrote.

"We think that the common practice of relying on 24-48 hours of monitoring for AF after a stroke or TIA of undetermined cause is insufficient and consider it an initial screen rather than a final test, especially given our finding that the yield of clinical follow-up alone as a means of detecting AF was negligible," they added.

In the other study, conventional follow-up was compared against heart rhythm monitoring using an insertable cardiac monitor (ICM) in 441 patients (mean age, 61.5 years) who recently had an ischemic stroke or TIA classified as cryptogenic. The ICM automatically detected and recorded AF, irrespective of heart rate or symptoms. Patients in the control group "underwent assessment at scheduled and unscheduled visits, with ECG monitoring performed at the discretion of the site investigator," said Dr. Tommaso Sanna of the Institute of Cardiology, Catholic University of the Sacred Heart, Rome, and his associates.

At 6 months, AF was detected in 8.9% of the 221 participants randomly assigned to the study intervention, compared with only 1.4% of the 220 control subjects. At 12 months, the AF detection rates were 12.4% and 2.0%, respectively. This difference in detection was consistent across all subgroups of patients, regardless of age, sex, race/ethnicity, type of index event, presence or absence of patent foramen ovale, and CHADS score, Dr. Sanna and his colleagues said (N. Engl. J. Med. 2014 June 26 [doi:10.1056/NEJMoa1313600])

As was observed in Dr. Gladstone’s study, the use of oral anticoagulants for secondary prevention more than doubled among patients who received an ICM. The benefit of the ICM strategy was clear: only 14 devices would need to be implanted to detect an episode of AF during 6 months of monitoring, only 10 devices to detect an episode of AF during 12 months of follow-up, and only 4 devices to detect an episode of AF during 36 months of follow-up, they noted.

The findings of both studies indicate that in current practice, a substantial number of patients labeled as having cryptogenic stroke or TIA actually have occult AF that goes undiagnosed and untreated.

Dr. Gladstone’s study was supported by the Canadian Stroke Network, the Heart and Stroke Foundation of Ontario, the Bastable-Potts Chair in Stroke, the Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, the University of Toronto, the Brain Sciences Program at Sunnybrook Health Sciences Centre, the Sunnybrook Research Institute, the Sam Sobara family, and the University of Toronto Brill Chair in Neurology. Dr. Gladstone reported receiving support from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer; his associates reported ties to numerous industry sources. Dr. Sanna’s study was supported by Medtronic, maker of the ICM used in the study. Dr. Sanna reported other ties to Medtronic, and his associates reported ties to numerous industry sources.

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Standard of care should now change

"Most patients with cryptogenic stroke or TIA should undergo at least several weeks of rhythm monitoring. Relatively inexpensive external loop recorders, such as those used in the [Gladstone] trial, will probably be cost-effective; the value of more expensive implantable loop recorders is less clear," he noted.The results of these two studies indicate that "prolonged monitoring of heart rhythm should now become part of the standard care of patients with cryptogenic stroke," said Dr. Hooman Kamel.

Dr. Kamel is in the department of neurology and the Feil Family Brain and Mind Research Institute at Cornell University, New York. He had no related financial disclosures. These remarks were taken from his editorial accompanying the reports by Dr. Gladstone and