Pub Date : 2025-11-01Epub Date: 2025-07-29DOI: 10.1016/j.carpath.2025.107760
Sungyeon Jung , Eun Na Kim , Hye In Lee , Hak Jae Kim , Jiwon Koh
Cardiac undifferentiated pleomorphic sarcomas (UPS) are extremely rare tumors that typically arise in the left atrium. They behave highly aggressively, requiring multimodality treatment when complete surgical resection is not feasible. Nevertheless, there is ongoing debate regarding the efficacy of adjuvant radiation therapy and the associated risk of radiation-induced cardiotoxicity. Pathologically, there is an emerging connection between cardiac UPS and intimal sarcoma of the great vessels, supported by morphological and genetic similarities. Here, we present the case of a 63-year-old woman diagnosed with a large right ventricular UPS. The patient underwent incomplete tumor resection, which was followed by post-operative radiotherapy. After nine months, her cardiac function deteriorated rapidly, and she ultimately ended up requiring heart transplantation. We discuss this case in the context of the existing literature on the diagnosis and treatment of cardiac UPS, focusing on the histopathologic features of the heart after radiotherapy.
{"title":"A case of cardiac undifferentiated pleomorphic sarcoma treated with post-operative radiotherapy followed by heart transplantation","authors":"Sungyeon Jung , Eun Na Kim , Hye In Lee , Hak Jae Kim , Jiwon Koh","doi":"10.1016/j.carpath.2025.107760","DOIUrl":"10.1016/j.carpath.2025.107760","url":null,"abstract":"<div><div>Cardiac undifferentiated pleomorphic sarcomas (UPS) are extremely rare tumors that typically arise in the left atrium. They behave highly aggressively, requiring multimodality treatment when complete surgical resection is not feasible. Nevertheless, there is ongoing debate regarding the efficacy of adjuvant radiation therapy and the associated risk of radiation-induced cardiotoxicity. Pathologically, there is an emerging connection between cardiac UPS and intimal sarcoma of the great vessels, supported by morphological and genetic similarities. Here, we present the case of a 63-year-old woman diagnosed with a large right ventricular UPS. The patient underwent incomplete tumor resection, which was followed by post-operative radiotherapy. After nine months, her cardiac function deteriorated rapidly, and she ultimately ended up requiring heart transplantation. We discuss this case in the context of the existing literature on the diagnosis and treatment of cardiac UPS, focusing on the histopathologic features of the heart after radiotherapy.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"79 ","pages":"Article 107760"},"PeriodicalIF":1.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-08-15DOI: 10.1016/j.carpath.2025.107765
Gregory A. Fishbein , Stephen D. Preston
{"title":"Revising the histopathologic definition of myocarditis: Birth of the seaport criteria","authors":"Gregory A. Fishbein , Stephen D. Preston","doi":"10.1016/j.carpath.2025.107765","DOIUrl":"10.1016/j.carpath.2025.107765","url":null,"abstract":"","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"79 ","pages":"Article 107765"},"PeriodicalIF":1.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-08-05DOI: 10.1016/j.carpath.2025.107763
Sarah Parsons, Hans H de Boer
Background: Diagnosing lymphocytic myocarditis in non-biopsy specimens remains challenging due to sampling variability, subjective interpretation of histology, and lack of standardized criteria. In 2025, the Society for Cardiovascular Pathology (SCVP) and the Association for European Cardiovascular Pathology (AECVP) proposed the "Seaport criteria" to address these limitations.
Objective: To assess the practical applicability of the Seaport criteria in a retrospective cohort of forensic autopsy cases with myocardial lymphocytic-predominant inflammation.
Methods: Ninety-three autopsy cases with lymphocytic-predominant myocardial inflammation were re-evaluated according to the Seaport criteria. Death in these cases was attributed to myocarditis (n = 45), unascertained causes (n = 34), or drug toxicity (n = 14). We assessed adherence to the recommended technical requirements, reclassified inflammation as diffuse, multifocal, focal myocarditis, or lymphocytic infiltrates of unknown significance (LIUS), and reviewed the original histological descriptions.
Results: Most cases (82 %) met the minimum technical sampling standards. Pediatric cases were disproportionately non-compliant with sampling requirements, but not due to insufficient myocardium being sampled. Original histological reporting varied substantially in terminology and detail, with myocyte injury inconsistently reported and a lack of sufficient information for grading under the Seaport criteria. Re-classification resulted in 36 cases of diffuse, 27 multifocal, 2 focal myocarditis, and 28 LIUS. The most common diagnosis in cases given myocarditis as the cause of death was diffuse myocarditis (33/45), whereas LIUS was most frequent in the drug-related and unascertained cohorts. Myocyte injury was sometimes difficult to interpret.
Conclusions: The Seaport criteria are feasible to classify lymphocytic myocarditis in autopsy hearts, with potential to standardize histological assessment and therefore improve diagnostic consistency. However, challenges remain in recognizing myocyte injury. Further prospective multicenter validation is recommended.
{"title":"The SCVP and AECVP 'Seaport criteria' for lymphocytic myocarditis: Retrospective application to an autopsy cohort.","authors":"Sarah Parsons, Hans H de Boer","doi":"10.1016/j.carpath.2025.107763","DOIUrl":"10.1016/j.carpath.2025.107763","url":null,"abstract":"<p><strong>Background: </strong>Diagnosing lymphocytic myocarditis in non-biopsy specimens remains challenging due to sampling variability, subjective interpretation of histology, and lack of standardized criteria. In 2025, the Society for Cardiovascular Pathology (SCVP) and the Association for European Cardiovascular Pathology (AECVP) proposed the \"Seaport criteria\" to address these limitations.</p><p><strong>Objective: </strong>To assess the practical applicability of the Seaport criteria in a retrospective cohort of forensic autopsy cases with myocardial lymphocytic-predominant inflammation.</p><p><strong>Methods: </strong>Ninety-three autopsy cases with lymphocytic-predominant myocardial inflammation were re-evaluated according to the Seaport criteria. Death in these cases was attributed to myocarditis (n = 45), unascertained causes (n = 34), or drug toxicity (n = 14). We assessed adherence to the recommended technical requirements, reclassified inflammation as diffuse, multifocal, focal myocarditis, or lymphocytic infiltrates of unknown significance (LIUS), and reviewed the original histological descriptions.</p><p><strong>Results: </strong>Most cases (82 %) met the minimum technical sampling standards. Pediatric cases were disproportionately non-compliant with sampling requirements, but not due to insufficient myocardium being sampled. Original histological reporting varied substantially in terminology and detail, with myocyte injury inconsistently reported and a lack of sufficient information for grading under the Seaport criteria. Re-classification resulted in 36 cases of diffuse, 27 multifocal, 2 focal myocarditis, and 28 LIUS. The most common diagnosis in cases given myocarditis as the cause of death was diffuse myocarditis (33/45), whereas LIUS was most frequent in the drug-related and unascertained cohorts. Myocyte injury was sometimes difficult to interpret.</p><p><strong>Conclusions: </strong>The Seaport criteria are feasible to classify lymphocytic myocarditis in autopsy hearts, with potential to standardize histological assessment and therefore improve diagnostic consistency. However, challenges remain in recognizing myocyte injury. Further prospective multicenter validation is recommended.</p>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":" ","pages":"107763"},"PeriodicalIF":1.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-07-10DOI: 10.1016/j.carpath.2025.107749
Marisa Prasanpanich , Majid Husain , Nancy J. Halnon , Richard Chang , Neda Zadeh , Jason Knight , Gregory A. Fishbein
Introduction
Barth syndrome is a mitochondrial disease caused by loss-of-function mutations in the TAFAZZIN gene located on chromosome Xq28 encoding a transacylase essential for cardiolipin remodeling. Most patients develop dilated cardiomyopathy and progressive heart failure within the first year of life with some requiring cardiac transplantation.
Case Report
A full-term male infant with an anatomically normal heart presented postnatally with cardiogenic shock necessitating VA-ECMO within the second day of life. WGS revealed a pathogenic c.703del (p.Ile235SerfsTer4) variant in the TAFAZZIN gene. While on the waitlist for cardiac transplantation, he was treated with intravenous Elamipretide, a mitochondrially-targeted tetrapeptide interacting with cardiolipin, without significant side effects, started at three weeks old and continued through transplantation. He underwent a successful orthotopic cardiac transplantation at five months of age. The explanted heart showed dilated left ventricle with hypertrabeculation and was remarkable for endocardial fibroelastosis and diffuse sarcoplasmic vacuolization with coarse granularity. Ultrastructurally, mitochondria displayed megaconia and replacement of cristae by circular, vesicular, cylindrical, and fingerprint-like structures. He continues to do well as an outpatient and remains on subcutaneous Elamipretide.
Summary
We describe a case of Barth syndrome harboring a novel pathogenic variant of the TAFAZZIN gene exhibiting dilated cardiomyopathy, hypertrabeculation, endocardial fibroelastosis, and prominent mitochondrial abnormality. Elamipretide was well tolerated.
{"title":"Cardiac pathology in a patient with a novel pathogenic variant c.703del (p.Ile235SerfsTer4) of the TAFAZZIN gene","authors":"Marisa Prasanpanich , Majid Husain , Nancy J. Halnon , Richard Chang , Neda Zadeh , Jason Knight , Gregory A. Fishbein","doi":"10.1016/j.carpath.2025.107749","DOIUrl":"10.1016/j.carpath.2025.107749","url":null,"abstract":"<div><h3>Introduction</h3><div>Barth syndrome is a mitochondrial disease caused by loss-of-function mutations in the <em>TAFAZZIN</em> gene located on chromosome Xq28 encoding a transacylase essential for cardiolipin remodeling. Most patients develop dilated cardiomyopathy and progressive heart failure within the first year of life with some requiring cardiac transplantation.</div></div><div><h3>Case Report</h3><div>A full-term male infant with an anatomically normal heart presented postnatally with cardiogenic shock necessitating VA-ECMO within the second day of life. WGS revealed a pathogenic c.703del (p.Ile235SerfsTer4) variant in the <em>TAFAZZIN</em> gene. While on the waitlist for cardiac transplantation, he was treated with intravenous Elamipretide, a mitochondrially-targeted tetrapeptide interacting with cardiolipin, without significant side effects, started at three weeks old and continued through transplantation. He underwent a successful orthotopic cardiac transplantation at five months of age. The explanted heart showed dilated left ventricle with hypertrabeculation and was remarkable for endocardial fibroelastosis and diffuse sarcoplasmic vacuolization with coarse granularity. Ultrastructurally, mitochondria displayed megaconia and replacement of cristae by circular, vesicular, cylindrical, and fingerprint-like structures. He continues to do well as an outpatient and remains on subcutaneous Elamipretide.</div></div><div><h3>Summary</h3><div>We describe a case of Barth syndrome harboring a novel pathogenic variant of the <em>TAFAZZIN</em> gene exhibiting dilated cardiomyopathy, hypertrabeculation, endocardial fibroelastosis, and prominent mitochondrial abnormality. Elamipretide was well tolerated.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"79 ","pages":"Article 107749"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To investigate the morphological variants of the leaflets and scallops of the mitral valve in fresh hearts of healthy individuals and to determine their morphometric values.
Methods
The hearts of 100 autopsy cases were analysed. The weight and dimensions of the heart and mitral valve circumference were measured. The morphology of the mitral leaflets and scallops and their hinge distances and heights were recorded.
Results
In 64 cases, classical leaflet morphology (aortic leaflet, mural leaflet consisting of 3 scallops, superolateral and inferoseptal commissures) was observed. In 24 cases accessory scallops and in 12 cases unified scallops were identified. The mean hinge distance and height of accessory scallops were 8.69±2.5 mm, and 9.79±2.5 mm respectively, and these values were 45.73±9.8 mm, and 11.95±2.3 mm in unified scallops, respectively. Accessory and unified scallops can be found in any region of mural leaflet, but the vast majority (96 %) are associated with it and more than half (60 %) are located at the commissural ends. In 1 case aortic leaflet consisted of two scallops and mural leaflet had 3 scallops in 63 %, 4 scallops in 22 %, 2 scallops in 8 %, 1 scallop in 4 % and 5 scallops in 3 %.
Conclusion
Significant morphological variations between mitral leaflets and scallops have been reported. These variations may affect the placement of the suture or device in mitral valve repair. It was also concluded that these variations cannot be predicted by age, gender or cardiac morphometry.
{"title":"Anatomical variations of the mitral leaflets: Unified and accessory scallops","authors":"Buse Naz ÇANDIR GÜRSES , Kader YILAR , Çağla ERGİN , Özcan GAYRETLİ","doi":"10.1016/j.carpath.2025.107767","DOIUrl":"10.1016/j.carpath.2025.107767","url":null,"abstract":"<div><h3>Aim</h3><div>To investigate the morphological variants of the leaflets and scallops of the mitral valve in fresh hearts of healthy individuals and to determine their morphometric values.</div></div><div><h3>Methods</h3><div>The hearts of 100 autopsy cases were analysed. The weight and dimensions of the heart and mitral valve circumference were measured. The morphology of the mitral leaflets and scallops and their hinge distances and heights were recorded.</div></div><div><h3>Results</h3><div>In 64 cases, classical leaflet morphology (aortic leaflet, mural leaflet consisting of 3 scallops, superolateral and inferoseptal commissures) was observed. In 24 cases accessory scallops and in 12 cases unified scallops were identified. The mean hinge distance and height of accessory scallops were 8.69±2.5 mm, and 9.79±2.5 mm respectively, and these values were 45.73±9.8 mm, and 11.95±2.3 mm in unified scallops, respectively. Accessory and unified scallops can be found in any region of mural leaflet, but the vast majority (96 %) are associated with it and more than half (60 %) are located at the commissural ends. In 1 case aortic leaflet consisted of two scallops and mural leaflet had 3 scallops in 63 %, 4 scallops in 22 %, 2 scallops in 8 %, 1 scallop in 4 % and 5 scallops in 3 %.</div></div><div><h3>Conclusion</h3><div>Significant morphological variations between mitral leaflets and scallops have been reported. These variations may affect the placement of the suture or device in mitral valve repair. It was also concluded that these variations cannot be predicted by age, gender or cardiac morphometry.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"79 ","pages":"Article 107767"},"PeriodicalIF":1.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Conduction system hamartoma (CSH) is a rare cardiac lesion characterized by the abnormal proliferation of Purkinje-like myocytes. It predominantly affects female infants and is often associated with sudden cardiac death. Recent studies have linked mitochondrial dysfunction, particularly complex I deficiency, with CSH. We report an autopsy case of an eight-month-old female infant who died suddenly following mild gastrointestinal symptoms. A gross examination revealed mild cardiac hypertrophy without nodular lesions. Histological analysis identified multifocal aggregates of Purkinje-like cells with clear or foamy cytoplasm, some forming well-circumscribed nodules in the non-compacted myocardium. Immunohistochemistry demonstrated a marked reduction in complex I expression, supporting mitochondrial dysfunction. Although prominent trabeculations and deep recesses suggestive of left ventricular noncompaction were observed, they did not meet the strict diagnostic criteria. This case supports the potential role of mitochondrial complex I deficiency as a key pathogenic mechanism in CSH and highlights the significance of detailed histopathological and immunohistochemical analyses for an accurate diagnosis, especially in cases of sudden unexplained infant death.
{"title":"Immuhistochemically-confirmed mitochondrial cardiomyopathy presenting as a conduction system hamartoma: A case report","authors":"Ryo Kaimori , Kentaro Sakai , Atsuhito Takeda , Rina Hayata , Shinji Yano , Haruto Nishida , Tsutomu Daa , Shinjiro Mori","doi":"10.1016/j.carpath.2025.107764","DOIUrl":"10.1016/j.carpath.2025.107764","url":null,"abstract":"<div><div>Conduction system hamartoma (CSH) is a rare cardiac lesion characterized by the abnormal proliferation of Purkinje-like myocytes. It predominantly affects female infants and is often associated with sudden cardiac death. Recent studies have linked mitochondrial dysfunction, particularly complex I deficiency, with CSH. We report an autopsy case of an eight-month-old female infant who died suddenly following mild gastrointestinal symptoms. A gross examination revealed mild cardiac hypertrophy without nodular lesions. Histological analysis identified multifocal aggregates of Purkinje-like cells with clear or foamy cytoplasm, some forming well-circumscribed nodules in the non-compacted myocardium. Immunohistochemistry demonstrated a marked reduction in complex I expression, supporting mitochondrial dysfunction. Although prominent trabeculations and deep recesses suggestive of left ventricular noncompaction were observed, they did not meet the strict diagnostic criteria. This case supports the potential role of mitochondrial complex I deficiency as a key pathogenic mechanism in CSH and highlights the significance of detailed histopathological and immunohistochemical analyses for an accurate diagnosis, especially in cases of sudden unexplained infant death.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"79 ","pages":"Article 107764"},"PeriodicalIF":1.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-08-18DOI: 10.1016/j.carpath.2025.107766
Jonathan K Lai , José Luis López-Guillén , Rae SM Yeung , Mamoru Ayusawa , Brian W McCrindle , Anita Nagy
Kawasaki disease (KD) is a systemic vasculitis of childhood that may lead to coronary artery aneurysms. Rupture of a giant coronary aneurysm is an exceptionally rare but often fatal complication. We report the case of a 4-month-old infant with treatment-resistant Kawasaki disease who developed rapidly enlarging giant aneurysms in all coronary artery branches despite aggressive immunomodulatory therapy. The patient died from cardiac tamponade due to rupture of a giant left anterior descending coronary artery aneurysm. Full autopsy revealed widespread vasculitis affecting multiple visceral arteries in addition to coronary artery involvement. Histological analysis demonstrated panarteritis with medial destruction and no evidence of thrombosis or myocardial infarction. A systematic review of reported cases demonstrated comparable clinical patterns and outcomes. This report underscores the potential for systemic vascular involvement in severe Kawasaki disease and highlights the importance of early recognition and intensified treatment in refractory cases.
{"title":"Fatal rupture of a giant left coronary artery aneurysm in an infant with Kawasaki disease. A case report with systematic literature review","authors":"Jonathan K Lai , José Luis López-Guillén , Rae SM Yeung , Mamoru Ayusawa , Brian W McCrindle , Anita Nagy","doi":"10.1016/j.carpath.2025.107766","DOIUrl":"10.1016/j.carpath.2025.107766","url":null,"abstract":"<div><div><strong>Kawasaki disease (KD)</strong> is a systemic vasculitis of childhood that may lead to coronary artery aneurysms. Rupture of a giant coronary aneurysm is an exceptionally rare but often fatal complication. We report the case of a 4-month-old infant with treatment-resistant Kawasaki disease who developed rapidly enlarging giant aneurysms in all coronary artery branches despite aggressive immunomodulatory therapy. The patient died from cardiac tamponade due to rupture of a giant left anterior descending coronary artery aneurysm. Full autopsy revealed widespread vasculitis affecting multiple visceral arteries in addition to coronary artery involvement. Histological analysis demonstrated panarteritis with medial destruction and no evidence of thrombosis or myocardial infarction. A systematic review of reported cases demonstrated comparable clinical patterns and outcomes. This report underscores the potential for systemic vascular involvement in severe Kawasaki disease and highlights the importance of early recognition and intensified treatment in refractory cases.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"79 ","pages":"Article 107766"},"PeriodicalIF":1.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144931572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-07-04DOI: 10.1016/j.carpath.2025.107750
Diwen Li , Shijun Hu , Xueyang Gong, Yiliya Ahemaiti, Luyao Wei, Yuyang Huang, Yan Liang, Yongyi Wang, Tianli Zhao
Bioprosthetic heart valves (BHVs) constructed from bovine pericardium (BP) are widely used in valve replacement due to their favorable biocompatibility. However, early structural degeneration, particularly in younger recipients, remains a critical challenge, primarily driven by calcification. Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite elevated by high-choline diets, has been implicated in vascular and valvular calcification, but its role in BHV deterioration remains unclear. This study aimed to evaluate the effects of TMAO on BP calcification. Three-week-old Sprague-Dawley rats were assigned to six diet groups: Normal Chow Diet (NCD), High Choline Diet (HCD), High Fat Diet (HFD), combined High Fat and Choline Diet (HFD+HCD), HFD with TMAO supplementation (HFD+TMAO), and HFD with both HCD and the TMAO inhibitor 3,3-dimethyl-1-butanol (DMB). BHVs made of BP were implanted subcutaneously, and after 8 weeks, we assessed calcium deposition, osteogenic markers, plasma metabolites, inflammatory cytokines, inflammatory cell proportions, and macrophage pyroptosis using techniques such as colorimetry, immunohistochemistry, ELISA, flow cytometry, and immunofluorescence. In vitro, RAW264.7 macrophages were exposed to TMAO, and pyroptosis was assessed by Western blotting, ELISA, and electron microscopy. Results indicated that HCD and HFD significantly increased BP calcification, osteogenic marker expression, and inflammatory responses in BHVs. The HFD+HCD and HFD+TMAO groups exhibited pronounced calcific and inflammatory effects, which were reduced by DMB. In vitro, TMAO induced macrophage pyroptosis, contributing to calcification. These findings suggest that TMAO promotes BP calcification through pyroptosis-driven inflammation, and that targeting TMAO via dietary or microbial modulation may offer a promising strategy to improve BHV durability, particularly in young patients.
{"title":"Trimethylamine N-oxide drives bioprosthetic heart valve calcification via macrophage pyroptosis in juvenile rats","authors":"Diwen Li , Shijun Hu , Xueyang Gong, Yiliya Ahemaiti, Luyao Wei, Yuyang Huang, Yan Liang, Yongyi Wang, Tianli Zhao","doi":"10.1016/j.carpath.2025.107750","DOIUrl":"10.1016/j.carpath.2025.107750","url":null,"abstract":"<div><div>Bioprosthetic heart valves (BHVs) constructed from bovine pericardium (BP) are widely used in valve replacement due to their favorable biocompatibility. However, early structural degeneration, particularly in younger recipients, remains a critical challenge, primarily driven by calcification. Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite elevated by high-choline diets, has been implicated in vascular and valvular calcification, but its role in BHV deterioration remains unclear. This study aimed to evaluate the effects of TMAO on BP calcification. Three-week-old Sprague-Dawley rats were assigned to six diet groups: Normal Chow Diet (NCD), High Choline Diet (HCD), High Fat Diet (HFD), combined High Fat and Choline Diet (HFD+HCD), HFD with TMAO supplementation (HFD+TMAO), and HFD with both HCD and the TMAO inhibitor 3,3-dimethyl-1-butanol (DMB). BHVs made of BP were implanted subcutaneously, and after 8 weeks, we assessed calcium deposition, osteogenic markers, plasma metabolites, inflammatory cytokines, inflammatory cell proportions, and macrophage pyroptosis using techniques such as colorimetry, immunohistochemistry, ELISA, flow cytometry, and immunofluorescence. In vitro, RAW264.7 macrophages were exposed to TMAO, and pyroptosis was assessed by Western blotting, ELISA, and electron microscopy. Results indicated that HCD and HFD significantly increased BP calcification, osteogenic marker expression, and inflammatory responses in BHVs. The HFD+HCD and HFD+TMAO groups exhibited pronounced calcific and inflammatory effects, which were reduced by DMB. In vitro, TMAO induced macrophage pyroptosis, contributing to calcification. These findings suggest that TMAO promotes BP calcification through pyroptosis-driven inflammation, and that targeting TMAO via dietary or microbial modulation may offer a promising strategy to improve BHV durability, particularly in young patients.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"79 ","pages":"Article 107750"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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