Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis

• Published in: Journal of the American College of Cardiology 2018-02, Vol.71 (8), p.860-871
• Main Authors: Treibel, Thomas A., Kozor, Rebecca, Schofield, Rebecca, Benedetti, Giulia, Fontana, Marianna, Bhuva, Anish N., Sheikh, Amir, López, Begoña, González, Arantxa, Manisty, Charlotte, Lloyd, Guy, Kellman, Peter, Díez, Javier, Moon, James C.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Aortic stenosis; Aortic valve; Aortic Valve Stenosis - diagnostic imaging; Aortic Valve Stenosis - surgery; Biomarkers; Biopsy; Brain natriuretic peptide; Calcium-binding protein; Cardiology; Cell size; Cellular structure; Cohort Studies; Concentration (composition); Coronary artery disease; Echocardiography; Electrocardiography; Extracellular matrix; Female; Fibrosis; Follow-Up Studies; Gadolinium; Heart; Heart diseases; Heart failure; Heart Valve Prosthesis Implantation - trends; Humans; Hypertrophy; left ventricular hypertrophy; Magnetic resonance; Male; Mercury; Middle Aged; Multimodal Imaging - methods; Patients; Plastics; Prospective Studies; Reduction; Rheumatic heart disease; Stenosis; Structure-function relationships; Troponin; Troponin T; Ventricle; Ventricular Remodeling - physiology
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2017.12.035

Left ventricular (LV) hypertrophy, a key process in human cardiac disease, results from cellular (hypertrophy) and extracellular matrix expansion (interstitial fibrosis). This study sought to investigate whether human myocardial interstitial fibrosis in aortic stenosis (AS) is plastic and can regress. Patients 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. At 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. Post-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) [Display omitted]