Histological and Histometric Characterization of Myocardial Fibrosis in End-Stage Hypertrophic Cardiomyopathy: A Clinical-Pathological Study of 30 Explanted Hearts.
Although noninvasively detected myocardial fibrosis (MF) has clinical implications in hypertrophic cardiomyopathy, the extent, type, and distribution of ventricular MF have never been extensively pathologically characterized. We assessed the overall amount, apex-to-base, circumferential, epicardial-endocardial distribution, pattern, and type of MF in 30 transplanted hearts of end-stage, hypertrophic cardiomyopathy.



Visual and morphometric histological analyses at basal, midventricular, and apical levels were performed. Overall MF ranged from 23.1% to 55.9% (mean=37.3±8.4%). Prevalent types of MF were as follows: replacement in 53.3%, interstitial-perimyocyte in 13.3%, and mixed in 33.3%. Considering left ventricular base-to-apex distribution, MF was 31.9%, 43%, and 46.2% at basal, midventricular, and apical level, respectively (P<0.001). Circumferential distributions (mean percentage of MF within the section) were as follows: anterior 11.9%, anterolateral 15.8%, inferolateral 7.0%, inferior 24.3%, anteroseptal 11%, midseptal 10.7%, and posteroseptal 11.4%; circumferential distributions for anterior and inferior right ventricular walls were 3.4% and 4.5%, respectively. Epicardial-endocardial distributions were as follows: trabecular 26.1% and subendocardial 20.2%, midwall 33.4%, and subepicardial 20.3%. Main patterns identified were as follows: midwall in 33.3% of the hearts, transmural in 23.3%, midwall-subepicardial in 23.3%, and midwall-subendocardial in 20%.



In end-stage, hypertrophic cardiomyopathy patients undergoing transplantation, more than one-third of the left ventricular myocardium was replaced by fibrosis, mainly of replacement type. MF preferentially involved the left ventricular apex and the midwall. Inferior and anterior walls and septum were maximally involved, whereas inferolateral and right ventricular were usually spared. These observations reflect the complex pathophysiology of hypertrophic cardiomyopathy and may provide clues for the timely recognition of disease progression by imaging techniques capable of quantifying MF.
From the Units of Cardiology (G.G., F.P., E.B., F.G., M.L., A.F., C.R.), Pathology (O.L., B.C., V.A.), Cardiac Surgery (E.P.), Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, S.Orsola-Malpighi University Hospital, Italy; and Referral Center for Cardiomyopathies, Cardiothoraco-vascular Department, Careggi University Hospital, Florence, Italy (I.O., F.C.).
Giuseppe
G
Galati
From the Units of Cardiology (G.G., F.P., E.B., F.G., M.L., A.F., C.R.), Pathology (O.L., B.C., V.A.), Cardiac Surgery (E.P.), Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, S.Orsola-Malpighi University Hospital, Italy; and Referral Center for Cardiomyopathies, Cardiothoraco-vascular Department, Careggi University Hospital, Florence, Italy (I.O., F.C.).
Ornella
O
Leone
From the Units of Cardiology (G.G., F.P., E.B., F.G., M.L., A.F., C.R.), Pathology (O.L., B.C., V.A.), Cardiac Surgery (E.P.), Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, S.Orsola-Malpighi University Hospital, Italy; and Referral Center for Cardiomyopathies, Cardiothoraco-vascular Department, Careggi University Hospital, Florence, Italy (I.O., F.C.).
Ferdinando
F
Pasquale
From the Units of Cardiology (G.G., F.P., E.B., F.G., M.L., A.F., C.R.), Pathology (O.L., B.C., V.A.), Cardiac Surgery (E.P.), Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, S.Orsola-Malpighi University Hospital, Italy; and Referral Center for Cardiomyopathies, Cardiothoraco-vascular Department, Careggi University Hospital, Florence, Italy (I.O., F.C.).
Iacopo
I
Olivotto
From the Units of Cardiology (G.G., F.P., E.B., F.G., M.L., A.F., C.R.), Pathology (O.L., B.C., V.A.), Cardiac Surgery (E.P.), Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, S.Orsola-Malpighi University Hospital, Italy; and Referral Center for Cardiomyopathies, Cardiothoraco-vascular Department, Careggi University Hospital, Florence, Italy (I.O., F.C.).
Elena
E
Biagini
From the Units of Cardiology (G.G., F.P., E.B., F.G., M.L., A.F., C.R.), Pathology (O.L., B.C., V.A.), Cardiac Surgery (E.P.), Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, S.Orsola-Malpighi University Hospital, Italy; and Referral Center for Cardiomyopathies, Cardiothoraco-vascular Department, Careggi University Hospital, Florence, Italy (I.O., F.C.).
Francesco
F
Grigioni
From the Units of Cardiology (G.G., F.P., E.B., F.G., M.L., A.F., C.R.), Pathology (O.L., B.C., V.A.), Cardiac Surgery (E.P.), Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, S.Orsola-Malpighi University Hospital, Italy; and Referral Center for Cardiomyopathies, Cardiothoraco-vascular Department, Careggi University Hospital, Florence, Italy (I.O., F.C.).
Emanuele
E
Pilato
From the Units of Cardiology (G.G., F.P., E.B., F.G., M.L., A.F., C.R.), Pathology (O.L., B.C., V.A.), Cardiac Surgery (E.P.), Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, S.Orsola-Malpighi University Hospital, Italy; and Referral Center for Cardiomyopathies, Cardiothoraco-vascular Department, Careggi University Hospital, Florence, Italy (I.O., F.C.).
Massimiliano
M
Lorenzini
From the Units of Cardiology (G.G., F.P., E.B., F.G., M.L., A.F., C.R.), Pathology (O.L., B.C., V.A.), Cardiac Surgery (E.P.), Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, S.Orsola-Malpighi University Hospital, Italy; and Referral Center for Cardiomyopathies, Cardiothoraco-vascular Department, Careggi University Hospital, Florence, Italy (I.O., F.C.).
Barbara
B
Corti
From the Units of Cardiology (G.G., F.P., E.B., F.G., M.L., A.F., C.R.), Pathology (O.L., B.C., V.A.), Cardiac Surgery (E.P.), Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, S.Orsola-Malpighi University Hospital, Italy; and Referral Center for Cardiomyopathies, Cardiothoraco-vascular Department, Careggi University Hospital, Florence, Italy (I.O., F.C.).
Alberto
A
Foà
From the Units of Cardiology (G.G., F.P., E.B., F.G., M.L., A.F., C.R.), Pathology (O.L., B.C., V.A.), Cardiac Surgery (E.P.), Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, S.Orsola-Malpighi University Hospital, Italy; and Referral Center for Cardiomyopathies, Cardiothoraco-vascular Department, Careggi University Hospital, Florence, Italy (I.O., F.C.).
Valentina
V
Agostini
From the Units of Cardiology (G.G., F.P., E.B., F.G., M.L., A.F., C.R.), Pathology (O.L., B.C., V.A.), Cardiac Surgery (E.P.), Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, S.Orsola-Malpighi University Hospital, Italy; and Referral Center for Cardiomyopathies, Cardiothoraco-vascular Department, Careggi University Hospital, Florence, Italy (I.O., F.C.).
Franco
F
Cecchi
From the Units of Cardiology (G.G., F.P., E.B., F.G., M.L., A.F., C.R.), Pathology (O.L., B.C., V.A.), Cardiac Surgery (E.P.), Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, S.Orsola-Malpighi University Hospital, Italy; and Referral Center for Cardiomyopathies, Cardiothoraco-vascular Department, Careggi University Hospital, Florence, Italy (I.O., F.C.). claudio.rapezzi@unibo.it.
Claudio
C
Rapezzi
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002312:Cardiomyopathy, Hypertrophic / Q000473:pathology* / Q000601:surgery; D002648:Child; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D006333:Heart Failure / Q000473:pathology* / Q000601:surgery; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000473:pathology* / Q000601:surgery; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D012189:Retrospective Studies; D055815:Young Adult
biomarkers; hypertrophic cardiomyopathy; magnetic resonance imaging; magnetic resonance spectroscopy; sudden cardiac death