Aortic stenosis rapid progression is associated with premature cardiac damage independently of baseline severity

Abstract Background Aortic stenosis (AS) is one of the major valvular heart diseases in developed countries. Degenerative fibrocalcific AS is a progressive disease of the valve and, ultimately, the myocardium. AS is a potentially fatal disease characterized not only by a narrowing of the aortic orifice but also by gradual cardiac damage (CD) that may extend beyond the left ventricle (LV). However, the presence and extent of extra-aortic cardiac damage did not reflect the baseline hemodynamic severity of AS in retrospective studies. Purpose This study aims to determine the rate of AS progression and its impact on cardiac damage and survival. Methods We retrospectively identified 914 patients (age 76 ± 8 years, 52% female, median follow-up time 6.8 years) with AS who had undergone > 1 echocardiogram. Bayesian hierarchical nonlinear models were used to predict aortic peak velocity as a function of time and estimate individual AS acceleration rates. Then, patients were clustered into rapid (RP) and slow progressors (SP) using machine learning algorithms. Results APV was best modeled by a logistic function of time. 483 patients were clustered as RP (53 %) and 431 as SP (47 %), with acceleration rate coefficients estimated at 0.14 ± 0.02 years-1 and 0.09 ± 0.02 years-1, respectively (p < 0.01). No association between progression rate and clinical variables was found. Compared with SP, RP had significantly higher 5-year incidences of LV damage, combined left atrium and mitral valve damage and combined tricuspid valve damage and pulmonary hypertension (all p ≤ 0.01). No statistically significant differences were seen for right ventricle damage between RP and SP, as the number of events was low. After multivariate adjustment for age, gender, comorbidities and baseline AS severity, RP remained an independent predictor for all extra-aortic cardiac damages except for the RV dysfunction. Importantly, baseline AS severity was not predictive of AS-related CD. RP was associated with higher mortality (HR 1.28, p = 0.02), persisting after adjustment for demographics, comorbidities, AS severity, and time-dependent aortic valve replacement (AVR) (HR = 1.36, p < 0.01). Conclusions RP may impair cardiac adaption to rapidly changing loading conditions, which induces premature cardiac damage that may not be reversible in the late stages of AS, when guideline-triggered interventions are currently delivered.