Myocardial Fibrosis and Reverse Remodeling After Valve Replacement in Chronic Aortic Regurgitation

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 (χ22 = 29.4; P < .001) and LVEDV at 7 months (χ21 = 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.