Analysis of ventricular remodeling in severe aoritic stenosis patients

Abstract

Introduction: Aortic stenosis (AS) is increasing worldwide and in Korea. Silent myocardial damage and fibrosis is common and therefore, detection of even subtle myocardial remodeling may be important for understanding the disease process and to establish an evidence-based treatment guideline. Methods: This series of analysis is based on a prospective cohort of moderate to severe AS patients. The patients in cohort 1 were severe AS patients with normal ejection fraction (EF) and divided into paradoxical low-flow (PLF-AS) and normal-flow AS (LF-AS) patients. Global longitudinal/circumferential strain (GLS/GCS) measured by 2D-speckle tracking imaging were compared between the two groups. The patients in cohort 2 underwent 2-dimensional echocardiography and cardiac magnetic resonance (CMR). The correlation between late gadolinium enhancement (LGE), EF and various LV functional parameters was analyzed. The patients in cohort 3 were severe AS patients with normal LVEF undergoing aortic valve replacement and endomyocardial biopsy. The specimens were stained with platelet-endothelial cell adhesion molecule-1 to investigate the correlation between myocardial vessel density and various echocardiographic parameters. Finally, minimally symptomatic moderate or severe AS patients with normal LVEF were enrolled in cohort 4. All underwent CMR including modified Look-Locker Inversion recovery sequence and the native T1 values were compared with various parameters of LV remodeling. Results: In patients enrolled to cohort 1, PLF-AS patients showed significantly impaired GLS in spite of preserved LVEF and the global LV afterload, represented by valvuloarterial impedance, was a significant determinant of GLS. In the patients enrolled to cohort 2, there was a significant trend towards adverse structural and functional remodeling in severe AS patients if there was either LGE or LV systolic dysfunction on CMR. Also, even if the LVEF was normal, those with LGE on CMR had significantly stiffer LV compared with those without. Analysis of the data from patients in cohort 3 revealed that the degree of myocardial angiogenesis correlates well with both LV systolic/diastolic function and the degree of LV hypertrophy. Also, there was a trend towards more myocardial angiogenesis with worsening of the LV geometry. Finally, in patients from cohort 4, native T1 value reflected the diffuse myocardial fibrosis degree and even in patients with minimal symptoms, patients with more diffuse myocardial fibrosis demonstrate a progressed degree of subclinical ventricular remodeling that was not reflected by the symptomatic status of the patient. Conclusion: These findings demonstrate that using 2D-speckle tracking imaging with echocardiography, LGE and native T1 with CMR, it may be possible to detect the subtle ventricular structural and functional remodeling in patients with severe AS, even those with normal LVEF. In addition, there seems to be a compensatory angiogenic process in the myocardium with worsening of the AS degree. These findings warrants further in-depth investigations into the process of LV remodeling in patients with severe AS and how it is related to patient outcome.