Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis

Abstract

BackgroundLeft ventricular (LV) hypertrophy, a key process in human cardiac disease, results from cellular (hypertrophy) and extracellular matrix expansion (interstitial fibrosis).ObjectivesThis study sought to investigate whether human myocardial interstitial fibrosis in aortic stenosis (AS) is plastic and can regress.MethodsPatients with symptomatic, severe AS (n = 181; aortic valve area index 0.4 ± 0.1 cm2/m2) were assessed pre–aortic valve replacement (AVR) by echocardiography (AS severity, diastology), cardiovascular magnetic resonance (CMR) (for volumes, function, and focal or diffuse fibrosis), biomarkers (N-terminal pro–B-type natriuretic peptide and high-sensitivity troponin T), and the 6-min walk test. CMR was used to measure the extracellular volume fraction (ECV), thereby deriving matrix volume (LV mass × ECV) and cell volume (LV mass × [1 − ECV]). Biopsy excluded occult bystander disease. Assessment was repeated at 1 year post-AVR.ResultsAt 1 year post-AVR in 116 pacemaker-free survivors (age 70 ± 10 years; 54% male), mean valve gradient had improved (48 ± 16 mm Hg to 12 ± 6 mm Hg; p < 0.001), and indexed LV mass had regressed by 19% (88 ± 26 g/m2 to 71 ± 19 g/m2; p < 0.001). Focal fibrosis by CMR late gadolinium enhancement did not change, but ECV increased (28.2 ± 2.9% to 29.9 ± 4.0%; p < 0.001): this was the result of a 16% reduction in matrix volume (25 ± 9 ml/m2 to 21 ± 7 ml/m2; p < 0.001) but a proportionally greater 22% reduction in cell volume (64 ± 18 ml/m2 to 50 ± 13 ml/m2; p < 0.001). These changes were accompanied by improvement in diastolic function, N-terminal pro–B-type natriuretic peptide, 6-min walk test results, and New York Heart Association functional class.ConclusionsPost-AVR, focal fibrosis does not resolve, but diffuse fibrosis and myocardial cellular hypertrophy regress. Regression is accompanied by structural and functional improvements suggesting that human diffuse fibrosis is plastic, measurable by CMR and a potential therapeutic target. (Regression of Myocardial Fibrosis After Aortic Valve Replacement; NCT02174471)

Diffuse myocardial fibrosis in adolescents operated with arterial switch for transposition of the great arteries - A CMR study

“…The presence of a normal LV mass with increased ECV, but apparently preserved cellular mass in our patients, could indicate a primary fibroblast activation rather than myocyte loss [30,31]. This is in contrast to a study on adult atrial switch corrected TGA individuals that showed increased ECV in the subpulmonary LV accompanied by decreased LV mass [25].…”

The effect of minimally invasive surgical aortic valve replacement on postoperative pulmonary and skeletal muscle function

“…Therefore, an enhanced left‐ventricular filling does not automatically result in enhanced cardiac output, at least not within a few weeks. According to the findings of Treibel et al ., systolic function, after sAVR, is known to improve only after a period of 6 months to 1 year due to the regression of cellular hypotrophy that is accompanied by structural, functional and biomarker improvement (Treibel et al., ). Therefore, changes in systolic function after mini‐AVR are not likely to be observed this early after surgery in the present study.…”

Clinical impact of pathology-proven etiology of severely stenotic aortic valves on mid-term outcomes in patients undergoing surgical aortic valve replacement

“…Based on our findings, we speculate that the valve etiology profiles might have some effects on the mid-term outcomes even after removal of the diseased valve. Such differences in late complications among the three groups may possibly stem from the extent of postoperative regression of diffuse myocardial fibrosis and myocardial cellular hypertrophy based on the aortic valve etiology, as investigated in a recent study [26]. Recently, calcific/degenerative AS has been understood to be an active disease process akin to atherosclerosis from the perspectives of compelling histopathological and clinical data [27].…”