Association of early cardiac remodeling and undiagnosed valvular heart disease in a population-based cohort

Background Subclinical valvular alterations may trigger myocardial remodeling and fibrotic processes before overt symptoms of heart failure or diastolic dysfunction occur. While advanced stages of valvular cardiomyopathy are well characterized, the impact of undiagnosed valvular disease on early myocardial remodeling in the general population remains insufficiently understood [1-4]. Purpose This study aims to identify the prevalence of early myocardial remodeling by imaging and biomarker parameters among individuals with undiagnosed left ventricular valvular heart disease. Methods We examined 2,588 participants from a population-based cohort with cardiac magnetic resonance imaging (CMR). Subclinical valvular heart disease (VHD) was defined as any echocardiographic or CMR evidence of aortic or mitral valve stenosis/regurgitation in the absence of VHD-history. Linear and logistic regression models were used to assess associations between VHD and cardiac structure and function as well as biomarkers. Models were adjusted for age, sex, and cardiovascular risk factors (body mass index, smoking status, diabetes, arterial hypertension, dyslipidemia). Results The median age was 67 years and 41% were women. Subclinical VHD was present in 988 (48%) participants, that were significantly older and showed higher rates of atrial fibrillation and heart failure compared to participants without findings of valvular dysfunction (Figure 1). In multivariable-adjusted linear regression analysis, VHD was independently associated with adverse cardiac remodeling, including reduced left ventricular (LV) ejection fraction (ß=-0.24; 95% confidence interval (CI) -0.33- -0.16; p<0.001), higher LV end-diastolic (ß=0.23; 95% CI 0.16-0.30; p<0.001) and end-systolic volumes (ß=0.27; 95% CI 0.17-0.37; p<0.001), and increased left atrial volume (ß=0.21; 95% CI 0.12-0.30; p<0.001). VHD was further associated with higher native myocardial T1 values (ß=0.15; 95% CI 0.06-0.25; p=0.003) and NT-proBNP (ß=0.23; 95% CI 0.15-0.31; p<0.001). In contrast, no associations were observed with extracellular volume fraction (ß=-0.09; 95% CI -0.22-0.04; p=0.19) or the presence of late gadolinium enhancement (odds ratio (OR)=1.00; 95% CI 0.74-1.35; p=0.99). Logistic regression models demonstrated a statistically significant increased odds of atrial fibrillation (OR=1.90; 95% CI 1.17-3.09; p=0.015) in VHD participants, but no strong associations with diastolic dysfunction (OR=0.86; 95% CI 0.66-1.13; p=0.29). Conclusion In this population-based cohort, undiagnosed VHD was independently associated with early structural and functional myocardial remodeling as well as NT-proBNP. Increased native T1 values in the absence of expanded extracellular volume fraction or focal fibrosis suggest early diffuse myocardial alterations preceding overt fibrotic remodeling. These findings support the potential clinical relevance of early detection of VHD at a preclinical stage.