{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:08:55Z","timestamp":1791493735436,"version":"4.3.4"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,4,16]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">The limited ability of enzyme replacement therapy (ERT) in removing globotriaosylceramide from cardiomyocytes is recognized for advanced Fabry disease cardiomyopathy (FDCM). Prehypertrophic FDCM is believed to be cured or stabilized by ERT. However, no pathologic confirmation is available. We report here on the long\u2010term clinical\u2013pathologic impact of ERT on prehypertrophic FDCM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Fifteen patients with Fabry disease with left ventricular maximal wall thickness \u226410.5\u2009mm at cardiac magnetic resonance required endomyocardial biopsy because of angina and ventricular arrhythmias. Endomyocardial biopsy showed coronary small\u2010vessel disease in the angina cohort, and vacuoles in smooth muscle cells and cardiomyocytes \u224820% of the cell surface containing myelin bodies at electron microscopy. Patients received \u03b1\u2010agalsidase in 8 cases, and \u03b2\u2010agalsidase in 7 cases. Both groups experienced symptom improvement except 1 patients treated with \u03b1\u2010agalsidase and 1 treated with \u03b2\u2010agalsidase. After ERT administration ranging from 4 to 20\u2009years, all patients had control cardiac magnetic resonance and left ventricular endomyocardial biopsy because of persistence of symptoms or patient inquiry on disease resolution. In 13 asymptomatic patients with FDCM, left ventricular maximal wall thickness and left ventricular mass, cardiomyocyte diameter, vacuole surface\/cell surface ratio, and vessels remained unchanged or minimally increased (left ventricular mass increased by &lt;2%) even after 20\u2009years of observation, and storage material was still present at electron microscopy. In 2 symptomatic patients, FDCM progressed, with larger and more engulfed by globotriaosylceramide myocytes being associated with myocardial virus\u2010negative lymphocytic inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">ERT stabilizes storage deposits and myocyte dimensions in 87% of patients with prehypertrophic FDCM. Globotriaosylceramide is never completely removed even after long\u2010term treatment. Immune\u2010mediated myocardial inflammation can overlap, limiting ERT activity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.123.032734","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T09:39:26Z","timestamp":1712050766000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Long\u2010Term Clinical\u2010Pathologic Results of Enzyme Replacement Therapy in Prehypertrophic Fabry Disease Cardiomyopathy"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5748-0725","authenticated-orcid":false,"given":"Andrea","family":"Frustaci","sequence":"first","affiliation":[{"name":"Cellular and Molecular Cardiology Lab IRCCS L. 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Giovanni Calibita Hospital Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Marchitelli","sequence":"additional","affiliation":[{"name":"Department of Radiological, Oncological, and Pathological Anatomy Sciences Sapienza University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Sansone","sequence":"additional","affiliation":[{"name":"Department of Human Sciences and Promotion of the Quality of Life San Raffaele Roma Open University Rome Italy"},{"name":"Laboratory of Molecular and Cellular Pathology IRCCS San Raffaele Roma Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9183-6206","authenticated-orcid":false,"given":"Manuel","family":"Belli","sequence":"additional","affiliation":[{"name":"Department of Human Sciences and Promotion of the Quality of Life San Raffaele Roma Open University Rome Italy"},{"name":"Laboratory of Molecular 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