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无症状性主动脉瓣狭窄的进展速率与超额死亡率相关。

Excess Mortality Associated with Progression Rate in Asymptomatic Aortic Valve Stenosis.

机构信息

Division of Cardiology, Department of Medicine, University of Verona, Verona, Italy.

Cardiology Service-CMSR Veneto Medica, Altavilla Vicentina, Vicenza, Italy.

出版信息

J Am Soc Echocardiogr. 2021 Mar;34(3):237-244. doi: 10.1016/j.echo.2020.11.015. Epub 2020 Nov 28.


DOI:10.1016/j.echo.2020.11.015
PMID:33253813
Abstract

BACKGROUND: Aortic valve stenosis (AS) is a progressive condition characterized by gradual calcification of the aortic cusps. Progression rate evaluated using echocardiography has been associated with survival. However, data from routine practice covering the whole spectrum of AS severity and the rate of symptom onset are sparse. The aim of this study was to assess outcomes under medical management related to disease progression in asymptomatic patients with a wide range of AS severity. METHODS: Two hundred twenty-nine consecutive asymptomatic patients (mean age, 77 ± 10 years; 55% men) with AS, preserved left ventricular ejection fraction, and two or more echocardiographic examinations performed from 2004 to 2014 were retrospectively included. The median time between the two echocardiographic examinations was 24 months (interquartile range, 15-46 months). Patients were identified as rapid progressors if the annualized difference in peak aortic velocity between two echocardiographic examinations was ≥0.3 m/sec/y; others were labeled as slow progressors. The primary end point was mortality during medical follow-up (censoring on aortic valve interventions). The secondary end point was overall mortality. RESULTS: Rapid progressors accounted for 67 of the 229 patients (29%), and this feature was not associated with baseline characteristics. During a median of 5.8 years (interquartile range, 3.4-8.3 years) of follow-up from the first echocardiographic examination, 102 patients (45%) died, 86 (84%) during medical follow-up. Rapid progression rate predicted excess mortality (vs slow progression rate) after adjustment for age, sex, symptoms, baseline left ventricular ejection fraction, and baseline aortic valve area (hazard ratio, 2.50; 95% CI, 1.48-4.21; P = .0006) and after adjusting for peak aortic velocity and left ventricular ejection fraction obtained at the last echocardiographic examination (hazard ratio, 2.07; 95% CI, 1.25-3.46; P = .005). Among patients with baseline peak aortic velocity < 4 m/sec (nonsevere AS), rapid progression rate was associated with higher 5-year mortality compared with slow progression (57% vs 22% [P < .0001] under medical management and 44% vs 18% [P = .005] overall). Outcomes were comparable between nonsevere AS rapid progressors and baseline severe AS. Progression rate showed incremental prognostic value on receiver operating characteristic curve analysis versus AS severity. Of note, among slow progressors, 11 patients (5%) presented with high rates of symptom development and poor outcomes related to ventricular dysfunction or other advanced AS features. CONCLUSIONS: Progression rate is an individual, almost unpredictable feature among patients with AS. Rapid progression is an incremental marker of excess mortality in asymptomatic patients with AS, independent of clinical and hemodynamic characteristics. Rapid progression rate may identify patients with nonsevere AS at higher risk for events.

摘要

背景:主动脉瓣狭窄(AS)是一种进行性疾病,其特征为主动脉瓣逐渐钙化。使用超声心动图评估的进展速度与生存率相关。然而,涵盖 AS 严重程度全谱和症状发作率的数据在常规实践中仍然很少。本研究旨在评估无症状患者在广泛的 AS 严重程度范围内接受药物治疗时与疾病进展相关的结局。

方法:连续纳入 229 例无症状患者(平均年龄 77±10 岁,55%为男性),这些患者具有 AS、左心室射血分数保留以及 2004 年至 2014 年之间进行的两次及以上超声心动图检查。两次超声心动图检查之间的中位时间为 24 个月(四分位距,15-46 个月)。如果两次超声心动图检查之间的峰值主动脉速度的年化差异≥0.3m/sec/y,则患者被归类为快速进展者;其他患者被归类为缓慢进展者。主要终点是药物治疗随访期间的死亡率(以主动脉瓣介入为截尾事件)。次要终点是总死亡率。

结果:在 229 例患者中,有 67 例(29%)为快速进展者,该特征与基线特征无关。在首次超声心动图检查后中位 5.8 年(四分位距,3.4-8.3 年)的随访期间,102 例患者(45%)死亡,86 例(84%)在药物治疗期间死亡。在调整年龄、性别、症状、基线左心室射血分数和基线主动脉瓣面积后,快速进展率预测死亡率增加(与缓慢进展率相比,危险比为 2.50;95%置信区间,1.48-4.21;P=0.0006);在调整最后一次超声心动图检查时获得的峰值主动脉速度和左心室射血分数后,该比值为 2.07(95%置信区间,1.25-3.46;P=0.005)。在基线峰值主动脉速度<4m/sec(非严重 AS)的患者中,与缓慢进展者相比,快速进展者的 5 年死亡率更高(药物治疗时为 57%比 22%[P<0.0001],总体为 44%比 18%[P=0.005])。非严重 AS 快速进展者与基线严重 AS 的结局相当。在接受者操作特征曲线分析中,进展率显示出比 AS 严重程度更优的预后价值。值得注意的是,在缓慢进展者中,有 11 例患者(5%)出现了症状快速发展和因心室功能障碍或其他晚期 AS 特征导致不良结局的高发生率。

结论:进展速度是 AS 患者中一个个体差异较大、几乎不可预测的特征。在无症状的 AS 患者中,快速进展是死亡率增加的一个额外标志物,独立于临床和血液动力学特征。快速进展率可能识别出处于较高风险的非严重 AS 患者。

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[2]
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J Am Heart Assoc. 2024-11-19

[3]
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Rev Cardiovasc Med. 2024-8-7

[4]
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[5]
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Physiol Rep. 2022-8

[6]
ANMCO position paper: 2022 focused update of appropriate use criteria for multimodality imaging: aortic valve disease.

Eur Heart J Suppl. 2022-5-18

[7]
Association of Annual N-Terminal Pro-Brain Natriuretic Peptide Measurements With Clinical Events in Patients With Asymptomatic Nonsevere Aortic Stenosis: A Post Hoc Substudy of the SEAS Trial.

JAMA Cardiol. 2022-4-1

[8]
Timing of Intervention in Asymptomatic Patients with Aortic Stenosis.

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[9]
Rapidly progressive aortic stenosis treated with transcatheter aortic valve implantation in a patient with Fabry disease: a case report.

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