Haemodynamic and metabolic phenotyping of patients with aortic stenosis and preserved ejection fraction: A specific phenotype of heart failure with preserved ejection fraction?

De Biase N; University of Pisa, Pisa, Italy
Mazzola M; Del Punta L; Di Fiore V; De Carlo M; Giannini C;
Costa G; Paneni F; Mengozzi A; Nesti L; Gargani L; Masi S; Pugliese NR

European Journal of Heart Failure. 25(11):1947-1958, 2023 11.

AIMS: Degenerative aortic valve stenosis with preserved ejection fraction
(ASpEF) and heart failure with preserved ejection fraction (HFpEF) display
intriguing similarities. This study aimed to provide a non-invasive,
comparative analysis of ASpEF versus HFpEF at rest and during exercise.
METHODS AND RESULTS: We prospectively enrolled 148 patients with HFpEF
and 150 patients with degenerative moderate-to-severe ASpEF, together with
66 age- and sex-matched healthy controls. All subjects received a
comprehensive evaluation at rest and 351/364 (96%) performed a combined
cardiopulmonary exercise stress echocardiography test. Patients with ASpEF
eligible for transcatheter aortic valve replacement (n = 125) also
performed cardiac computed tomography (CT). HFpEF and ASpEF patients
showed similar demographic distribution and biohumoral profiles. Most
patients with ASpEF (134/150, 89%) had severe high-gradient aortic
stenosis; 6/150 (4%) had normal-flow, low-gradient ASpEF, while 10/150
(7%) had low-flow, low-gradient ASpEF. Both patient groups displayed
significantly lower peak oxygen consumption (VO2 ), peak cardiac output,
and peak arteriovenous oxygen difference compared to controls (all p <
0.01). ASpEF patients showed several extravalvular abnormalities at rest
and during exercise, similar to HFpEF (all p < 0.01 vs. controls).
Epicardial adipose tissue (EAT) thickness was significantly greater in
ASpEF than HFpEF and was inversely correlated with peak VO2 in all groups.
In ASpEF, EAT was directly related to echocardiography-derived disease
severity and CT-derived aortic valve calcium burden.
CONCLUSION: Functional capacity is similarly impaired in ASpEF and HFpEF
due to both peripheral and central components. Further investigation is
warranted to determine whether extravalvular alterations may affect
disease progression and prognosis in ASpEF even after valve intervention,
which could support the concept of ASpEF as a specific sub-phenotype of