Low-flow in aortic valve stenosis patients with reduced ejection fraction does not depend on left ventricular...

Area of Science:

• Cardiology
• Cardiovascular Imaging
• Genomics

Background:

• Severe aortic stenosis (AS) with reduced left ventricular ejection fraction (LVEF) presents distinct high-gradient (HG) and low-gradient (LG) subgroups.
• Underlying pathophysiological mechanisms and characteristics of these subgroups remain incompletely understood.

Purpose of the Study:

• To investigate the clinical, histological, and genetic characteristics differentiating HG-AS from LG-AS patients with reduced LVEF.
• To elucidate the hemodynamic mechanisms contributing to the low-flow state in LG-AS.

Main Methods:

• A multimodal approach was used, including clinical data, histology, next-generation sequencing (NGS), echocardiography, and cardiovascular magnetic resonance (CMR) imaging.
• 98 patients with AS and reduced LVEF were analyzed, with biopsy samples assessed for fibrosis and mRNA expression.

Main Results:

• No significant differences in LVEF, LV mass, or end-diastolic LV diameter were observed between HG-AS (n=40) and LG-AS (n=58) subgroups.
• Myocardial fibrosis and global gene expression patterns did not differ between the HG-AS and LG-AS groups.
• Mitral regurgitation, atrial fibrillation, and impaired right ventricular function were significantly more frequent in LG-AS patients, potentially explaining higher mortality.

Conclusions:

• Low transaortic gradient and cardiac output in low-flow severe aortic stenosis are not primarily driven by left ventricular dysfunction or global gene expression changes.
• Additional cardiac pathologies, including mitral regurgitation, atrial fibrillation, and right ventricular dysfunction, are key contributors to the LG-AS phenotype.
• These comorbidities should be considered in the management and planning of aortic valve replacement for LG-AS patients.