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The influence of calcific aortic stenosis on atrioventricular conduction: a prospective observational study and Mendelian randomization

Rao, K.; Ciofani, J. L.; Han, D. S.; Nazarzadeh, M.; Rahimi, K.; Baer, A.; Saad, N.; Litkouhi, P. N.; Allahwala, U.; Hansen, P. S.; Bhindi, R.

2024-05-10 cardiovascular medicine
10.1101/2024.05.08.24307094 medRxiv
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BackgroundAortic stenosis (AS) may prolong atrioventricular (AV) conduction secondary to calcium infiltration of the atrioventricular-His-pathway, which is hypothesized to contribute to bradyarrhythmia and sudden cardiac death in this cohort. This study investigates the correlation between calcific AS and impaired AV conduction. MethodsWe performed an observational study and Mendelian randomization (MR). The observational study was a sub-analysis on AS patients undergoing transcatheter aortic valve implantation2021-2023). Regression analyses were used to assess the association between aortic valve calcium volumes with electrophysiology study derived markers of AV conduction. The primary MR analyses used European-ancestry genome-wide association studies for AS (653,867 participants,13,765 cases) and PR interval (271,570 participants). The exposure outcome was the genetic liability for AS, whilst the outcome was prolonged PR interval or AV block. ResultsThe mean age in the observational study (n=196) was 81.8 years, 64.8% were men, and 46(23.6%) had first-degree heart block. There was no significant association between total aortic valve complex calcium volume and first-degree heart block, or with PR, AH or HV intervals. On MR, no association was found between genetic liability for AS and PR interval (beta -0.41, 95%CI -1.33-0.51, p=0.38). Additional analyses evaluating genetic liability for AS and AV block suggested a significant association on IVW analysis (OR 1.15, 95%CI 1.02-1.30, p=0.02), but this was not supported by sensitivity analyses and thus interpreted with caution. ConclusionsThis study found no meaningful association between aortic valve calcification and PR, AH or HV interval, challenging the hypothesis that calcific AS impairs atrioventricular conduction.

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