Left Ventricular Systolic Dysfunction in Aortic Stenosis: Pathophysiology, Diagnosis, Management, and Future Directions

Degenerative calcific aortic stenosis (AS) is the most common valvular heart disease and often co-exists with left ventricular (LV) systolic dysfunction at the time of diagnosis. Impaired LV systolic function has been associated with worse outcomes in the setting of AS, even after successful aortic valve replacement (AVR). Myocyte apoptosis and myocardial fibrosis are the 2 key mechanisms responsible for the transition from the initial adaptation phase of LV hypertrophy to the phase of heart failure with reduced ejection fraction. Novel advanced imaging methods, based on echocardiography and cardiac magnetic resonance imaging, can detect LV dysfunction and remodeling at an early and reversible stage, with important implications for the optimal timing of AVR especially in patients with asymptomatic severe AS. Furthermore, the advent of transcatheter AVR as a first-line treatment for AS with excellent procedural outcomes, and evidence that even moderate AS portends worse prognosis in heart failure with reduced ejection fraction patients, has raised the question of early valve intervention in this patient popu-lation. With this review, we describe the pathophysiology and outcomes of LV systolic dysfunction in the setting of AS, present imaging predictors of LV recovery after AVR, and discuss future directions in the treatment of AS extending beyond the traditional indications defined in the current guidelines. ARB, angiotensin receptor blockers; AS, aortic stenosis; AV, aortic valve; AVR, aortic valve replacement; CMR, cardiac magnetic resonance; ECV, extracellular volume; EF, ejection fraction; GLS, global longitudinal strain; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; hsTnI, high-sensitivity troponin I; LFLG, low-flow low-gradient; LGE, late gadolinium enhancement; LV, left ventricle/left ventricular; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy; LVMi, left ventricular mass index; RAS, renin-angiotensin system; SAVR, surgical aortic valve replacement; TAVR, transcatheter aortic valve replacement.