https://doi.org/10.1007/s00392-024-02526-y
1Universitätsklinikum Bonn Medizinische Klinik und Poliklinik II Bonn, Deutschland
Background:
Aortic stenosis (AS) is a progressive valvular disease characterized by calcification of the aortic cusps. While severe AS has been extensively studied, the natural history and clinical implications of mild to moderate AS remain less well understood. Early stages of the disease often present a diagnostic challenge, as patients may remain asymptomatic for years, with a variable rate of progression to severe AS. Identifying patients at higher risk of rapid progression could allow for timely intervention. However, the factors influencing the progression of AS and the impact of mild to moderate stages on outcomes are not fully elucidated.
Purpose:
We aimed to evaluate the rate and time course of progression of AS and to identify possible risk factors associated with this progression. Moreover, we sought to assess the impact of mild or moderate AS on outcomes.
Methods:
The study included 307 patients diagnosed with mild to moderate AS, recruited between 2019 and 2023. Echocardiography was performed on all participants at baseline and at six-month intervals. Additionally, a biochemical evaluation was conducted at each visit. The primary endpoints were the progression rate of AS - defined by changes in echocardiographic parameters indicative of AS severity over time - and all-cause mortality.
Results:
The mean age of our study population was 74.1±10.7 years, with 37.8% being female. Of the included patients, 204 (66.4%) were diagnosed with mild AS, and 103 (33.6%) with moderate AS. The baseline characteristics were well balanced between patients with mild and moderate AS, with comparable ages (73.4±11.0 vs 75.3±10.1 years, p=0.16), left ventricular ejection fraction (58.7±8.5 vs 58.3±8.4%, p=0.64) as well as phosphate (1.10±0.23 vs 1.13±0.24 mg/dL, p=0.29) and calcium levels (2.35±0.15 vs 2.32±0.14 mg/dL, p=0.18). Moreover, the median STS-PROM risk score was comparable between patients with mild AS (2.4%) and moderate AS (2.4%, p=0.52). Overall, progression of AS by at least one degree was observed in 145 (47.2%) patients with a median time interval of 511 days (IQR: 243 – 865 days). Among patients with mild AS, progression occurred in 94 (46.1%) cases, compared to 51 (49.5%) cases with moderate AS (p=0.63). Progression of AS was associated with significantly increased baseline phosphate levels (p=0.02) and inflammation parameters, as indicated by elevated C-reactive protein levels (p=0.02). The overall one-year all-cause mortality was 8.8%, significantly higher in patients with moderate AS compared to those with mild AS (13.6% vs 6.4%, p=0.05). Kaplan-Meier survival analysis revealed that this difference was persistent over the follow-up period of two years (p=0.04), as presented in Figure 1. Cox proportional hazards modeling showed that moderate AS was significantly associated with increased mortality (p=0.04).
Conclusion:
This study underscores the progression risk in patients with mild to moderate AS, with nearly half progressing within 17 months. Progression was linked to increased phosphate levels and inflammation, suggesting potential predictors for disease advancement. Significantly, moderate AS patients showed higher mortality rates than those with mild AS. These findings highlight the need for regular monitoring and suggest that targeted interventions based on identified risk factors could improve patient outcomes, emphasizing the critical role of early identification and management in enhancing the patient’s prognosis.