Sherrill Clay, Port Jenna, Wahoud Mohamad, Koethe Ben, Mohanty Sharanya, Downey Brian C, Patel Ayan, Wessler Benjamin S
Department of Medicine, Tufts Medical Center, 800 Washington St, Boston, MA, 02111, USA.
Department of Medicine, Tufts Medical Center, Cardiovascular Center, 800 Washington St, Boston, MA, 02111, USA.
Echo Res Pract. 2025 Aug 4;12(1):19. doi: 10.1186/s44156-025-00086-z.
BACKGROUND: Transthoracic echocardiography (TTE) is used to assess aortic stenosis (AS) severity and track disease progression. As the field moves to study medical therapies to halt disease progression, reliable non-invasive imaging markers that are sensitive to small changes in disease progression are needed to enable efficient trial designs. The signal-to-noise ratio of commonly obtained TTE-based measures of progressive (non-severe) AS severity is unknown. METHODS: This is a retrospective study of TTEs done at a tertiary referral centre (Tufts Medical Center, Boston MA). A cohort of patients with progressive AS who had two TTEs done within 30 days (in the absence of valve intervention) and a cohort of progressive AS patients with TTEs ≥ 1 year apart, also without valvular intervention, were assembled. Limits of agreement (LOA) and intraclass correlation (ICC) were calculated for aortic valve area (AVA) by continuity equation, peak velocity, and mean gradient. Cohen's d-statistic (d) was calculated for each hemodynamic assessment and a composite marker to assess sensitivity for detecting disease progression normalised to measurement variability. RESULTS: The reproducibility cohort included 24 patients. The progression cohort included 35 patients. The median age was 70 years (interquartile range [IQR] 13). 22 patients (37.3%) were female. In the progression cohort, the median time between TTEs was 2.2 years (IQR 3.1 years). In the reproducibility cohort, AVA LOA were -0.7 to 0.8, ICC = 0.61; peak velocity LOA were -149.0 to + 126.7, ICC = 0.29; and mean gradient LOA were -16.2 to 12.2, ICC = 0.06. The d-statistic for annualised change in AVA was -0.29, the d-statistic for annualised change in maximum velocity was 0.46, the d-statistic for mean gradient was 0.55. The d-statistic for a composite, including all three hemodynamic markers, was 0.45. CONCLUSIONS: Standard TTE markers of AS severity have variable sensitivity for detecting AS progression. For patients with progressive (non-severe) AS, mean gradient has the highest signal-to-noise ratio and may be the most reliable TTE-based assessment of disease progression.
背景：经胸超声心动图（TTE）用于评估主动脉瓣狭窄（AS）的严重程度并追踪疾病进展。随着该领域转向研究阻止疾病进展的医学疗法，需要可靠的非侵入性成像标志物，这些标志物对疾病进展的微小变化敏感，以实现高效的试验设计。基于TTE的常见渐进性（非重度）AS严重程度测量指标的信噪比尚不清楚。 方法：这是一项在三级转诊中心（马萨诸塞州波士顿塔夫茨医学中心）进行的TTE回顾性研究。收集了一组在30天内进行了两次TTE（无瓣膜干预）的渐进性AS患者，以及一组TTE间隔≥1年且同样无瓣膜干预的渐进性AS患者。通过连续性方程、峰值速度和平均梯度计算主动脉瓣面积（AVA）的一致性界限（LOA）和组内相关系数（ICC）。计算每个血流动力学评估指标以及一个综合标志物的科恩d统计量（d），以评估检测疾病进展的敏感性，并根据测量变异性进行标准化。 结果：重复性队列包括24例患者。进展队列包括35例患者。中位年龄为70岁（四分位间距[IQR]为13）。22例患者（37.3%）为女性。在进展队列中，两次TTE之间的中位时间为2.2年（IQR为3.1年）。在重复性队列中，AVA的LOA为-0.7至0.8，ICC = 0.61；峰值速度的LOA为-149.0至+126.7，ICC = 0.29；平均梯度的LOA为-16.2至12.2，ICC = 0.06。AVA年化变化的d统计量为-0.29，最大速度年化变化的d统计量为0.46，平均梯度的d统计量为0.55。包括所有三个血流动力学标志物的综合标志物的d统计量为0.45。 结论：AS严重程度的标准TTE标志物在检测AS进展方面具有不同的敏感性。对于渐进性（非重度）AS患者，平均梯度具有最高的信噪比，可能是基于TTE的最可靠的疾病进展评估指标。
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