Thornton GD; Institute of Cardiovascular Science University College London, UK
Bennett JB; Aziminia N; Tapia L; Birkinshaw A; et al
JAMA Cardiology. 11(10):981-990, 2026 Oct 01
Importance: Patients undergoing aortic valve replacement (AVR) for chronic
severe aortic regurgitation (AR) based on current guideline-based
thresholds may have irreversible myocardial scarring.
Objective: To quantify reverse remodeling, functional recovery, and
symptomatic change after AVR and assess whether myocardial fibrosis is
associated with incomplete recovery.
Design, Setting, and Participants: In this prospective longitudinal
observational study, patients with chronic severe AR referred for AVR by a
cardiology team were included. Key exclusion criteria were previous valve
surgery, moderate or greater valve disease, and other primary
cardiomyopathies. Included patients underwent paired biomarkers,
echocardiography, cardiopulmonary exercise testing, and cardiovascular
magnetic resonance (CMR) at baseline and at a median of 7 months after
AVR. The study took place at 2 tertiary cardiothoracic centers in London,
United Kingdom, with enrollment from August 2021 to October 2023. Data
were analyzed from January to April 2026.
Exposure: AVR.
Main Outcomes and Measures: Left ventricular (LV) reverse remodeling
(change in LV end-diastolic volume [LVEDV] and LV mass) post-AVR and
preoperative correlates of incomplete recovery, with prespecified focus on
CMR fibrosis markers (late gadolinium enhancement [LGE] and extracellular
volume [ECV]).
Results: Seventy-two patients (median [IQR] age, 60 [6-70] years; 59
[82%] male, 35 [49%] with bicuspid aortic valve) completed paired studies.
Median (IQR) regurgitant volume fell from 61 (38-83) mL to 5 (3-8) mL;
median (IQR) LVEDV fell 44% from 273 (211-307) mL to 153 (130-177) mL; and
median (IQR) LV mass fell 21% from 200 (159-226) g to 158 (137-184) g (all
P < .001). Indexed intracellular volume declined 21% and indexed
extracellular volume 15% (26 mL/m2 to 22 mL/m2; P < .001), raising
extracellular volume fraction (ECV%) from 27.4% to 29.1% (P < .001). LGE
as a percentage of LV mass was unchanged (2.3% to 2.4%; P = .36); baseline
LGE burden was associated with less regression of LV mass (chi22 = 29.4; P
< .001) and LVEDV at 7 months (chi21 = 7.9; P = .007). New York Heart
Association class and quality of life improved (median [IQR] EQ-5D index
improved from 0.89 [0.78-1.00] to 0.94 [0.81-1.00]; P < .001), but maximum
oxygen consumption was unchanged (22.6 mL/kg/min to 21 mL/kg/min; P =
.08). N-terminal pro-B-type natriuretic peptide decreased slightly (228
pg/mL to 198 pg/mL; P = .27), with a larger fall in patients with evidence
of decompensation (n = 31; 469 pg/mL to 279 pg/mL; P = .02).
Conclusions and Relevance: In this study, AVR was associated with
substantial reverse remodeling at 7 months, including regression of
hypertrophy and a fall in indexed extracellular (matrix) volume; the
extracellular volume fraction rose, as cellular regression outpaced matrix
regression. Focal scar, as a proportion of myocardium, was unchanged.
Preoperative focal scar was independently associated with less recovery
and may mark incomplete remodeling. Objective functional recovery did not
improve at this time point.