Advertisement

Additional diagnostic value of electron microscopic examination in endomyocardial biopsy in patients with suspected non-ischemic cardiomyopathy

Published:October 10, 2022DOI:https://doi.org/10.1016/j.jjcc.2022.09.012

      Highlights

      • The diagnostic value of electron microscopic examination in endomyocardial biopsy
      • Detection rate of specific histological findings according to cardiac morphology
      • Electron microscopic examination in Fabry disease and cardiac amyloidosis

      Abstract

      Background

      Electron microscopy enables a finely detailed analysis of ultra-structural features, and hence, it generally has an added diagnostic value to light microscopy alone. However, no studies have verified the additional diagnostic value of electron microscopic examination in patients with suspected non-ischemic cardiomyopathy.

      Methods

      A total of 294 consecutive patients with non-ischemic cardiomyopathy who underwent endomyocardial biopsy were prospectively enrolled. Patients were divided into three groups according to left ventricular morphology assessed using echocardiography. Myocardial specimens were collected from the right ventricular septum and examined by light microscopy. Electron microscopy was performed subsequently to evaluate the additional diagnostic value.

      Results

      Altogether, 294 patients were analyzed, including 160 (55 %), 96 (33 %), and 35 (12 %) patients who were diagnosed with primary, secondary, and unclassified cardiomyopathy, respectively. In patients with dilated cardiomyopathy-like morphology, the detection rate of disease-specific histological findings was relatively low compared to that in patients with other cardiac morphologies. The additional diagnostic value of electron microscopy was observed in eight patients, including five with Fabry disease, one with cardiac amyloidosis, one with mitochondrial cardiomyopathy, and one with triglyceride deposit cardiomyovasculopathy. Among the 18 cardiac amyloidosis cases, electron microscopy detected amyloid fibrils in all patients, whereas light microscopy could not detect amyloid deposition in 1 patient. Among one of five patients with Fabry disease, light microscopy did not show obvious vacuolated cardiomyocytes, but zebra bodies were detected by electron microscopy, leading to the diagnosis of cardiac Fabry disease. The diagnostic value of electron microscopic examination in patients with cardiac sarcoidosis was not observed.

      Conclusions

      The additional diagnostic value of electron microscopy was observed in patients with secondary cardiomyopathy, in whom light microscopy did not show disease-specific histological findings. Electron microscopy should be performed in cases where secondary cardiomyopathy is strongly suspected with no disease-specific findings by light microscopy.

      Graphical abstract

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Kitaoka H.
        • Tsutsui H.
        • Kubo T.
        • Ide T.
        • Chikamori T.
        • Fukuda K.
        • et al.
        JCS/JHFS 2018 guideline on the diagnosis and treatment of cardiomyopathies.
        Circ J. 2021; 85: 1590-1689
        • Elliott P.
        • Andersson B.
        • Arbustini E.
        • Bilinska Z.
        • Cecchi F.
        • Charron P.
        • et al.
        Classification of the cardiomyopathies: a position statement from the European Society of Cardiology working group on myocardial and pericardial diseases.
        Eur Heart J. 2008; 29: 270-276
        • Maron B.J.
        • Towbin J.A.
        • Thiene G.
        • Antzelevitch C.
        • Corrado D.
        • Arnett D.
        • et al.
        Contemporary definitions and classification of the cardiomyopathies: an American Heart Association scientific statement from the council on clinical cardiology, heart failure and transplantation committee; quality of care and outcomes research and functional genomics and translational biology interdisciplinary working groups; and council on epidemiology and prevention.
        Circulation. 2006; 113: 1807-1816
        • Seferovic P.M.
        • Tsutsui H.
        • McNamara D.M.
        • Ristic A.D.
        • Basso C.
        • Bozkurt B.
        • et al.
        Heart failure association, Heart Failure Society of America, and japanese heart failure society position statement on endomyocardial biopsy.
        J Card Fail. 2021; 27: 727-743
        • Cooper L.T.
        • Baughman K.L.
        • Feldman A.M.
        • Frustaci A.
        • Jessup M.
        • Kuhl U.
        • et al.
        The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the american College of Cardiology, and the european Society of Cardiology Endorsed by the Heart Failure Society of America and the heart failure Association of the European Society of cardiology.
        Eur Heart J. 2007; 28: 3076-3093
        • Saito T.
        • Asai K.
        • Tachi M.
        • Sato S.
        • Mozawa K.
        • Adachi A.
        • et al.
        Long-term prognostic value of ultrastructural features in dilated cardiomyopathy: comparison with cardiac magnetic resonance.
        ESC Heart Fail. 2020; 7: 682-691
        • Saito T.
        • Asai K.
        • Sato S.
        • Takano H.
        • Mizuno K.
        • Shimizu W.
        Ultrastructural features of cardiomyocytes in dilated cardiomyopathy with initially decompensated heart failure as a predictor of prognosis.
        Eur Heart J. 2015; 36: 724-732
        • Takemura G.
        • Takatsu Y.
        • Ono K.
        • Miyatake T.
        • Ono M.
        • Izumi T.
        • et al.
        Usefulness of electron microscopy in the diagnosis of cardiac sarcoidosis.
        Heart Vessels. 1995; 10: 275-278
        • Baandrup U.
        • Florio R.A.
        • Roters F.
        • Olsen E.G.
        Electron microscopic investigation of endomyocardial biopsy samples in hypertrophy and cardiomyopathy. A semiquantitative study in 48 patients.
        Circulation. 1981; 63: 1289-1298
        • Leone O.
        • Veinot J.P.
        • Angelini A.
        • Baandrup U.T.
        • Basso C.
        • Berry G.
        • et al.
        2011 consensus statement on endomyocardial biopsy from the Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology.
        Cardiovasc Pathol. 2012; 21: 245-274
        • Terasaki F.
        • Azuma A.
        • Anzai T.
        • Ishizaka N.
        • Ishida Y.
        • Isobe M.
        • et al.
        JCS 2016 guideline on diagnosis and treatment of cardiac sarcoidosis- digest version.
        Circ J. 2019; 83: 2329-2388
        • Imaizumi Y.
        • Eguchi K.
        • Imada H.
        • Hidano K.
        • Niijima S.
        • Kawata H.
        • et al.
        Electron microscopy of contact between a monocyte and a multinucleated giant cell in cardiac sarcoidosis.
        Can J Cardiol. 2016; 32: e19-e20
        • Kitaoka H.
        • Izumi C.
        • Izumiya Y.
        • Inomata T.
        • Ueda M.
        • Kubo T.
        • et al.
        JCS 2020 guideline on diagnosis and treatment of cardiac amyloidosis.
        Circ J. 2020; 84: 1610-1671
        • Lang R.M.
        • Badano L.P.
        • Mor-Avi V.
        • Afilalo J.
        • Armstrong A.
        • Ernande L.
        • et al.
        Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the european Association of Cardiovascular Imaging.
        J Am Soc Echocardiogr. 2015; 28e14
        • Daimon M.
        • Watanabe H.
        • Abe Y.
        • Hirata K.
        • Hozumi T.
        • Ishii K.
        • et al.
        Normal values of echocardiographic parameters in relation to age in a healthy japanese population: the JAMP study.
        Circ J. 2008; 72: 1859-1866
        • Caforio A.L.
        • Pankuweit S.
        • Arbustini E.
        • Basso C.
        • Gimeno-Blanes J.
        • Felix S.B.
        • et al.
        Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the european Society of Cardiology Working Group on myocardial and pericardial diseases.
        Eur Heart J. 2013; 34 (48a-48d)2636–48
        • Kadosawa K.
        • Morikawa T.
        • Konishi Y.
        Zebra bodies without fabry disease or hydroxychloroquine.
        Clin Exp Nephrol. 2021; 25: 94-96
        • Sperati C.J.
        • Rosenberg A.Z.
        Hydroxychloroquine-induced mimic of renal fabry disease.
        Kidney Int. 2018; 94: 634
        • Sakuraba H.
        • Tsukimura T.
        • Tanaka T.
        • Togawa T.
        • Takahashi N.
        • Mikami D.
        • et al.
        Clinical and biochemical investigation of male patients exhibiting membranous cytoplasmic bodies in biopsied kidney tissues; a pitfall in diagnosis of fabry disease.
        J Nephropathol. 2015; 4: 91-96
        • Uemura A.
        • Morimoto S.
        • Hiramitsu S.
        • Kato Y.
        • Ito T.
        • Hishida H.
        Histologic diagnostic rate of cardiac sarcoidosis: evaluation of endomyocardial biopsies.
        Am Heart J. 1999; 138: 299-302
        • Casella M.
        • Pizzamiglio F.
        • Dello Russo A.
        • Carbucicchio C.
        • Al-Mohani G.
        • Russo E.
        • et al.
        Feasibility of combined unipolar and bipolar voltage maps to improve sensitivity of endomyocardial biopsy.
        Circ Arrhythm Electrophysiol. 2015; 8: 625-632