Tan Joshua Teik Ann, He George Shiyao, Chia Jolene Li Ling, Tan Gladys Qiao Xuan, Teo Yao Neng, Teo Yao Hao, Syn Nicholas L, Chai Ping, Wong Raymond C C, Yeo Tiong-Cheng, Kong William K F, Poh Kian-Keong, Sia Ching-Hui
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Department of Medicine, National University Hospital, Singapore, Singapore.
Clin Res Cardiol. 2025 Mar;114(3):350-367. doi: 10.1007/s00392-024-02465-8. Epub 2024 Jul 15.
Current guidelines on the management strategy for patients with asymptomatic severe aortic stenosis (AS) remain unclear. This uncertainty stems from the lack of data regarding the natural history of these patients. To address this gap, we performed a systematic review and meta-analysis examining the natural history of asymptomatic severe AS patients receiving conservative treatment.
The PubMed, Cochrane, and Embase databases were searched from inception to 24 January 2024 using the keywords "asymptomatic" AND "aortic" AND "stenosis". We included studies examining patients with asymptomatic severe AS. In interventional trials, only data from conservatively managed arms were collected. A one-stage meta-analysis was conducted using individual patient data reconstructed from published Kaplan-Meier curves. Sensitivity analysis was performed for major adverse cardiovascular outcomes in patients who remained asymptomatic throughout follow-up.
A total of 46 studies were included (n = 9545). The median time to the development of symptoms was 1.11 years (95% CI 0.90-1.53). 49.36% (40.85-58.59) of patients who were asymptomatic had suffered a major adverse cardiovascular event by 5 years. The median event-free time for heart failure hospitalization (HFH) was 5.50 years (95% CI 5.14-5.91) with 36.34% (95% CI 33.34-39.41) of patients experiencing an HFH by year 5. By 5 years, 79.81% (95% CI 69.26-88.58) of patients developed symptoms (angina, dyspnoea, syncope and others) and 12.36% (95% CI 10.01-15.22) of patients died of cardiovascular causes. For all-cause mortality, the median survival time was 9.15 years (95% CI 8.50-9.96) with 39.43% (CI 33.41-36.40) of patients dying by 5 years. The median time to AVR was 4.77 years (95% CI 4.39-5.17), with 52.64% (95% CI 49.85-55.48) of patients requiring an AVR by 5 years.
Our results reveal poor cardiovascular outcomes for patients with asymptomatic severe AS on conservative treatment. A significant proportion eventually requires an AVR. Further research is needed to determine if early intervention with AVR is more effective than conservative treatment.
目前关于无症状重度主动脉瓣狭窄（AS）患者管理策略的指南仍不明确。这种不确定性源于缺乏这些患者自然病史的数据。为填补这一空白，我们进行了一项系统评价和荟萃分析，以研究接受保守治疗的无症状重度AS患者的自然病史。
使用关键词“无症状”“主动脉”“狭窄”，在PubMed、Cochrane和Embase数据库中从建库至2024年1月24日进行检索。我们纳入了研究无症状重度AS患者的研究。在干预性试验中，仅收集保守治疗组的数据。使用从已发表的Kaplan-Meier曲线重建的个体患者数据进行单阶段荟萃分析。对在整个随访期间仍无症状的患者的主要不良心血管结局进行敏感性分析。
共纳入46项研究（n = 9545）。出现症状的中位时间为1.11年（95%CI 0.90 - 1.53）。49.36%（40.85 - 58.59）的无症状患者在5年内发生了主要不良心血管事件。因心力衰竭住院（HFH）的无事件中位时间为5.50年（95%CI 5.14 - 5.91），到第5年有36.34%（95%CI 33.34 - 39.41）的患者发生HFH。到5年时，79.81%（95%CI 69.26 - 88.58）的患者出现症状（心绞痛、呼吸困难、晕厥等），12.36%（95%CI 10.01 - 15.22）的患者死于心血管原因。对于全因死亡率，中位生存时间为9.15年（95%CI 8.50 - 9.96），到5年时有39.43%（CI 33.41 - 36.40）的患者死亡。进行主动脉瓣置换术（AVR）的中位时间为4.77年（95%CI 4.39 - 5.17），到5年时52.64%（95%CI 49.85 - 55.48）的患者需要进行AVR。
我们的结果显示，接受保守治疗的无症状重度AS患者的心血管结局较差。很大一部分患者最终需要进行AVR。需要进一步研究以确定早期AVR干预是否比保守治疗更有效。
