Aortic valve stenosis is unrelated to the severity of transthyretin amyloid cardiomyopathy and is instead linked to aging
A Okada, A Kuwahara, S Kurashima, Y Irie, K Moriuchi, M Amano, M Amaki, H Kanzaki, T Kitai, C IzumiAbstract
Background
Concomitant aortic stenosis (AS) is not uncommon in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). However, the underlying pathophysiology linking these two conditions remains unclear. Furthermore, the prevalence and clinical impact of concomitant "non-severe" AS, including aortic valve sclerosis, in ATTR-CM remain unclear. In this study, we evaluated 1) the association between the severity of AS/aortic valve sclerosis and the severity of ATTR-CM, and 2) the prognostic impact of non-severe AS in patients diagnosed with ATTR-CM.
Methods
This single-center retrospective study evaluated 202 consecutive patients with ATTR-CM encountered at our institution between 2014 and 2025. Six patients without echocardiographic data at diagnosis were excluded, and 196 patients were analyzed. Transaortic peak velocity was evaluated by echocardiography when a restricted aortic valve motion was observed, and was used to define AS/aortic valve sclerosis severity. Prognostic follow-up began at the time of diagnosis. The endpoint of the study was defined as a composite of all-cause mortality or heart failure hospitalization. When patients received aortic valve intervention before experiencing the endpoint, they were handled as not reaching the endpoint and were censored at the time of intervention.
Results
AS or aortic valve sclerosis was observed in 65/196 (33%) of patients, which included peak velocity 1.0-1.9 m/s N=46; 2.0-2.9 m/s N=13; 3.0 m/s or greater N=6. As shown in Figure 1, there were no clear trends indicating that the severity of the aortic valve lesions were associated with the severity of ATTR-CM, as evaluated by biomarkers (troponin T, B-type natriuretic peptides, and estimated glomerular filtration rate) and echocardiographic parameters (ejection fraction, left ventricular mass, and septal e’) used in amyloidosis staging and previous reports. Instead, the severity of aortic valve lesions showed a clear association with older age. During a median follow-up of 1.9 [0.7-4.3] years, the composite endpoint occurred in 54 patients. Three patients underwent aortic valve intervention. The incidence of the composite endpoint was higher in patients with greater transaortic peak velocity (Figure 2).
Conclusions
Our findings suggest that the severity of AS/aortic valve sclerosis is not associated with the severity of ATTR-CM, as assessed by biomarkers and echocardiographic parameters included in amyloidosis staging and previous reports. Instead, it was clearly associated with aging, indicating that aging may be the primary contributor to AS in patients with ATTR-CM. Greater transaortic peak velocity, even in the non-severe range, was associated with a higher incidence of all-cause mortality or heart failure hospitalization. These results provide additional insight into the pathophysiology underlying the coexistence of AS and ATTR-CM.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.