郑刚教授：心脏植入式电子设备记录的房颤负荷与死亡率相关
虽然近年来在房颤治疗和预防方面取得了一定的进展，但房颤的全球负担仍在继续上升[1]。既往研究提示房颤与死亡率升高相关，但这些研究大多依赖于房颤的行政索赔数据或临床特征，或存在房颤低负担相关偏倚或诊断不足等问题[2-12]。既往研究证实，与无房颤患者相比，持续时间≥6分钟的亚临床房颤与更高的卒中风险相关，且进行口服抗凝治疗或可降低卒中风险[13-15]。房颤类别（阵发性房颤、持续性房颤或永久性房颤）相关的试验也证实，房颤与健康结局密切相关，但现有关于房颤与死亡率关系的研究多将房颤进行二重分类[10-12,16-21]。因此，目前尚无通过高度可靠的房颤检测方法测量不同类型房颤与死亡率之间关联的数据，进一步了解真正的房颤相关死亡率对预防和治疗工作至关重要。
心脏植入式电子设备（CIED）提供了敏感且特异的长期连续的心律监测装置，可用于房颤诊断和房颤负担评估。近期，Circulation发布的一项研究旨在评估设备诊断的房颤患者与无房颤患者间校正后的累计死亡率差异，并评估设备诊断的阵发性房颤、持续性房颤和永久性房颤患者间的累计死亡率差异。
作者：郑刚 泰达国际心血管病医院
本文为作者授权医脉通发布，未经授权请勿转载。
该研究使用了Optum Clinformatics US索赔数据库，确定了植入CIED后传输数据≥6个月的患者。在植入后的前6个月（基线期）评估房颤负荷。根据索赔数据评估随后的死亡率，比较房颤患者和非房颤患者的死亡率，并对年龄、地理区域、保险类型、Charlson合并症指数和植入年份进行调整。
研究结果显示，在分析的21391名患者（年龄72.9±10.9岁；56.3%男性）中，7798名（36.5%）患有设备识别房颤。
在平均22.4±12.9个月的随访中，总死亡率为13.5%。校正后，与无房颤患者相比，设备诊断的房颤与随访22.4个月期间的较高的全因死亡率相关，且非阵发性房颤患者的累计死亡率最高。
由于研究控制了许多可能影响死亡率的人口统计学和临床协变量，包括CCI和CHA2DS2-VASc评分，因此当前研究的结果表明了设备识别的房颤的存在与房颤负担类别对全因死亡率的影响之间的关联。基于既往索赔和队列的分析表明，房颤患者的死亡率更高，高危人群的1年死亡率接近19.5%[17,20,24]。此外，既往个体研究和荟萃分析已经确定，与阵发性房颤相比，非阵发性房颤的死亡风险更高[11,18,25-26]。然而，文献中可归因于房颤的死亡率范围广泛，这可能受到对房颤临床或索赔诊断的依赖性的影响[26-29]。房颤的临床识别可能会忽略无症状或短暂的房颤发作，这仍然会对患者的整体健康产生重大影响。
既往研究表明，在缺乏长期、连续的节律监测的情况下，房颤负担类别的临床分类容易出错[7,13,14]。当前研究通过证明衍生声明和设备识别的房颤负担类型之间的一致性较低，对这些数据进行了扩展[7]。通过使用设备识别的房颤对房颤的存在和类别进行分类，该分析对CIED患者中设备识别的房颤与死亡率之间的关联提供了可靠的估计。
由于2项前瞻性试验的结果表明，亚临床房颤发作的抗凝治疗与房颤相关血栓栓塞事件的减少有关，因此使用设备识别的房颤而非临床诊断来确定房颤的存在和房颤负担类别的程度具有特别的相关性[13-14]。为了克服基于索赔的房颤自我评价的局限性，既往的几项研究也评估了选择人群中设备识别的房颤与死亡率之间的关系[10,12]。具体而言，在对39710名CIED患者的分析中，所有患者都有医疗保险索赔诊断的房颤，证明了房颤负担与1年死亡率之间的剂量-反应关系[10]。
尽管既往多项项研究也显示了房颤负担增加与死亡率之间的关联，但本研究在几个特定方面是独特的。首先，由于房颤是一种对心肌基质有渐进性影响的慢性疾病，时间跨度对探究房颤对死亡率的中期影响至关重要[30]。本研究通过随访的最大允许持续时间来评估死亡率，而不是审查1年的数据，更加可靠性。此外，该研究并非专门评估临床诊断为阵发性房颤的患者，而是分析所有具有CIED的患者，以便进行无房颤、阵发性房颤、持续性房颤和永久性房颤患者的比较。结合既往数据，该研究结果表明，任何形式的房颤负担增加都与CIED患者的更高死亡率相关。
与之前的研究不同，研究进行了按CIED类型的亚组分析，以进一步确定样本中房颤的存在与死亡率之间的关联。事实上，在使用永久性起搏器、除颤起搏器（ICD）、心脏再同步治疗-除颤器和植入式心电检测仪（ICM）设备的亚组中，房颤的存在仍然与较高的校正后全因死亡率相关。特别值得注意的是，患有设备识别房颤的ICM患者的死亡率更高，因为这些患者通常与需要CIED进行起搏或除颤的患者没有相同的共病特征和死亡率风险。尽管在心脏再同步治疗-起搏器患者中，房颤的存在与死亡率之间没有关联，但效果的方向和大致大小与其他设备类型一致。因此，缺乏统计显著性很可能是由于该亚群内的患者数量较低（占总样本的3.4%）。由于单一CIED类型中每个房颤负担类别的患者数量相对较低，因此没有进行确定房颤类别与死亡率之间相关性的分析。
此外，目前的研究报告了基线时卒中预防和节律控制干预的发生率和随访中的死亡率。校正后的分析表明，在永久性房颤患者的随访中，基线时开具口服抗凝药（OAC）处方与较低的死亡风险相关，但在阵发性房颤患者、持续性房颤患者或所有房颤患者中则不相关。这些结果产生了假设，表明基线时房颤负担可能存在阈值效应，从而从OAC处方中获得死亡率益处。
总之，目前的分析表明，在控制了许多人口统计学和临床协变量后，房颤的存在，特别是非阵发性房颤与更高的死亡率相关。由于既往研究已经证明，心律控制对心衰人群的房颤（从而降低房颤负担）具有死亡率益处[31-33]，因此，当前研究的结果产生了假设，表明降低房颤负荷的心律控制干预措施可能会给所有CIED患者带来死亡率益处。需要进一步的研究来评估完全预防房颤或限制其进展的策略是否会影响所有的死亡率[34]。
此外，本研究也存在一定的局限性，如本研究为回顾性，且纳入患者为单一药厂登记的患者等。此外，本研究也无法提供死因相关信息，无法为房颤和死亡之间的相关性提供更准确的信息。
本研究随访22.4个月显示，在控制了大量人口统计学和临床协变量后，设备诊断的房颤与较高的全因死亡率相关；且在房颤患者中，非阵发性房颤患者的累计死亡率最高。
未来仍需进一步研究以评估房颤预防策略对死亡率的影响。
郑刚 教授
•现任泰达国际心血管病医院特聘专家，济兴医院副院长
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