Cardiovascular Pathology最新文献

{"title":"Cardiac pathology in a patient with a novel pathogenic variant c.703del (p.Ile235SerfsTer4) of the TAFAZZIN gene","authors":"Marisa Prasanpanich ,&nbsp;Majid Husain ,&nbsp;Nancy J. Halnon ,&nbsp;Richard Chang ,&nbsp;Neda Zadeh ,&nbsp;Jason Knight ,&nbsp;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":"2025-07-10","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}

{"title":"Trimethylamine N-oxide drives bioprosthetic heart valve calcification via macrophage pyroptosis in juvenile rats","authors":"Diwen Li ,&nbsp;Shijun Hu ,&nbsp;Xueyang Gong,&nbsp;Yiliya Ahemaiti,&nbsp;Luyao Wei,&nbsp;Yuyang Huang,&nbsp;Yan Liang,&nbsp;Yongyi Wang,&nbsp;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":"2025-07-04","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}

{"title":"Lymphocytic myocarditis: A histopathologic definition and classification from the society for cardiovascular pathology and association for European cardiovascular pathology. II: Surgical and autopsy specimens","authors":"Joseph J. Maleszewski ,&nbsp;Jytte Banner ,&nbsp;Hans de Boer ,&nbsp;Monica De Gaspari ,&nbsp;Michael C. Fishbein ,&nbsp;Sarah Parsons ,&nbsp;Barbara Sampson ,&nbsp;Mary N. Sheppard ,&nbsp;Allard C. Van der Wal ,&nbsp;James R. Stone ,&nbsp;Katarzyna Michaud","doi":"10.1016/j.carpath.2025.107748","DOIUrl":"10.1016/j.carpath.2025.107748","url":null,"abstract":"<div><h3>Background and aim</h3><div>Lymphocytic myocarditis, characterized by lymphocyte-predominant myocardial inflammation with associated myocyte injury, is a term that has decades-old histopathologic criteria when encountered on endomyocardial biopsy. However, the interpretation of non-biopsy specimens such as surgical resections and autopsy samples has lacked standardized histopathologic criteria, despite their growing clinical and forensic relevance. The aim was to develop and establish criteria for the diagnosis and classification of lymphocytic myocarditis in non-biopsy ventricular myocardial specimens.</div></div><div><h3>Methods and results</h3><div>An international panel of cardiovascular pathologists representing the Society for Cardiovascular Pathology (SCVP) and the Association for European Cardiovascular Pathology (AECVP) developed a new classification system, which was completed at a final meeting in the Seaport area of Boston. These “Seaport” criteria for non-biopsy specimens formally define lymphocytic myocarditis as myocardial inflammation predominantly composed of lymphocytes, accompanied by myocyte injury not attributable to other causes. Recommendations address specimen type, technical handling, diagnostic thresholds, and qualifiers of chronicity. Diagnostic categories include active myocarditis and lymphocytic infiltrate of uncertain significance (LIUS). The document also outlines the interpretive challenges in attributing causality in autopsy settings, provides guidance on the use of ancillary techniques, and highlights the limitations of current histopathologic approaches.</div></div><div><h3>Conclusion</h3><div>These consensus-based criteria offer a standardized framework for diagnosing lymphocytic myocarditis in non-biopsy specimens. Adoption of these guidelines is expected to improve diagnostic consistency, enhance research comparability, and inform clinical and forensic evaluations. Future efforts should aim to refine definitions of myocyte injury, validate ancillary techniques, and elucidate the clinical significance of inflammation in the absence of injury.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"78 ","pages":"Article 107748"},"PeriodicalIF":2.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526525","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}

{"title":"Aorto-pericardial fistula in an intravenous drug addict with infective endocarditis of the aortic valve","authors":"Petr Handlos ,&nbsp;Klára Handlosová ,&nbsp;Vladimír Židlík ,&nbsp;Vladimíra Gebauerová ,&nbsp;Matěj Uvíra","doi":"10.1016/j.carpath.2025.107747","DOIUrl":"10.1016/j.carpath.2025.107747","url":null,"abstract":"<div><div>This paper presents a fatal case of a 31-year-old female intravenous amphetamine user in the late stage of pregnancy who suffered a sudden collapse at home. The autopsy revealed hemopericardium resulting from an aorto-pericardial fistula. Histological examination of the aortic valve revealed multiple abscesses. Moreover, the histological examination also proved the presence of foreign bodies in the fistula and a granulomatous reaction with numerous multinucleated giant cells surrounding the bodies in the wall of the aorto-pericardial fistula necrosis as well as purulent phlegmonous inflammation. The foreign bodies were positive for amphetamine and methamphetamine. These findings suggest that the aorto-pericardial fistula developed due to intravenous drug abuse.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"78 ","pages":"Article 107747"},"PeriodicalIF":2.3,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483244","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}

{"title":"Vegetations and cerebral emboli of non-bacterial thrombotic endocarditis are overwhelmingly platelet-dominant: A possible histological clue for the diagnosis from an autopsy study","authors":"Tomoyuki Otani ,&nbsp;Chiyoko Terada-Ikeda ,&nbsp;Junpei Koge ,&nbsp;Hisao Shimizu ,&nbsp;Manabu Matsumoto ,&nbsp;Kisaki Amemiya ,&nbsp;Yoshihiko Ikeda ,&nbsp;Keiko Ohta-Ogo ,&nbsp;Emi Date ,&nbsp;Norishige Iizuka ,&nbsp;Akihiko Yoshizawa ,&nbsp;Kinta Hatakeyama","doi":"10.1016/j.carpath.2025.107746","DOIUrl":"10.1016/j.carpath.2025.107746","url":null,"abstract":"<div><div>As endovascular therapy for ischemic stroke has advanced, we are getting increasing opportunities to study cerebral thromboemboli histologically. These opportunities have not been fully exploited, but some reports suggest that thromboemboli retrieved from cancer patients with stroke are platelet-richer than those from non-cancer patients. Nonbacterial thrombotic endocarditis (NBTE) is an important cause of ischemic stroke in cancer patients. In this study, we analyzed 20 autopsy cases of NBTE (13 of which had advanced cancer), along with cases of cerebral embolism associated with atrial fibrillation (AF, <em>n</em> = 11) and infective endocarditis (IE, <em>n</em> = 7). The histological features of NBTE vegetations (<em>n</em> = 20) were fairly consistent among cases: they were overwhelmingly platelet-dominant and spatially homogeneous, containing few erythrocytes or inflammatory cells. They were little organized, if at all, and were not associated with valvular destruction. Cerebral emboli associated with NBTE (<em>n</em> = 7) were also platelet-dominant. Intracardiac thrombi/vegetations and cerebral emboli associated with AF and IE, in contrast, contained variable amounts of platelets and erythrocytes. NBTE vegetations/emboli, compared with AF thrombi/emboli, had significantly higher %platelet area (intracardiac vegetations/thrombi: 70 ± 15 % vs 33 ± 20 %, <em>p</em> &lt; 0.001; cerebral emboli: 65 ± 16 % vs 25 ± 22 %, <em>p</em> &lt; 0.001) and lower %erythrocyte area (vegetations/thrombi: 9 ± 7 % vs 61 ± 21 %, <em>p</em> &lt; 0.001; emboli: 20 ± 11 % vs 70 ± 9 %, <em>p</em> &lt; 0.001). These results suggest that some platelet-rich thrombi retrieved during mechanical thrombectomy for ischemic stroke in cancer patients are likely to have originated from NBTE. Clinical diagnosis of NBTE is often difficult, but histological analysis of retrieved thrombi may help identify this underdiagnosed condition.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"78 ","pages":"Article 107746"},"PeriodicalIF":2.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336318","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}

{"title":"A renal transplant recipient with a pulmonic valve mass","authors":"Ilyse Darwish ,&nbsp;Benoît de Varennes ,&nbsp;Pierre Olivier Fiset ,&nbsp;Sophie Camilleri-Broët ,&nbsp;Vynka Lash ,&nbsp;Marcelo Cantarovich ,&nbsp;Todd C. Lee ,&nbsp;Cecilia T. Costiniuk","doi":"10.1016/j.carpath.2025.107745","DOIUrl":"10.1016/j.carpath.2025.107745","url":null,"abstract":"<div><div>A 43-year-old female with a renal transplant presented with fatigue, dyspnea, anemia, and thrombocytopenia. Chest CT revealed pulmonary nodules, and transthoracic echocardiography identified a large, multi-lobulated, multi-cystic mass attached to the pulmonic valve. Pathology demonstrated fungal hyphae, and bronchoalveolar lavage (BAL) fluid grew <em>Aspergillus fumigatus</em>, with a serum Aspergillus galactomannan (GM) antigen index of 1.95. The pulmonic valve was excised and a bioprosthetic valve was inserted. The patient was treated with voriconazole. Pulmonic valve <em>Aspergillus</em> endocarditis (AE) is a rare condition associated with high mortality. Given the rising number of transplant recipients, heightened clinical vigilance is warranted in this population.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"78 ","pages":"Article 107745"},"PeriodicalIF":2.3,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301172","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}

{"title":"Increased angiogenesis and lymphangiogenesis in rheumatic mitral valves","authors":"Paavo Immonen ,&nbsp;Pranita Zare ,&nbsp;Ari Mennander ,&nbsp;Timo Paavonen ,&nbsp;Pradeep Vaideeswar ,&nbsp;Ivana Kholová","doi":"10.1016/j.carpath.2025.107744","DOIUrl":"10.1016/j.carpath.2025.107744","url":null,"abstract":"<div><div>Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) create a global burden in the field of cardiovascular medicine due to significant morbidity and mortality, particularly in low- and middle-income countries and the underprivileged population.</div><div>Sequential surgical specimens of mitral valves excised from 19 patients with moderate to marked rheumatic mitral stenosis were included in this study and compared to eight sequential surgical myxomatous degenerative valves (control). The study group population had a mean age of 43.8 (± standard deviation (SD) 13.3) years and comprised 10 female and nine male patients. The controls included three female and five male patients with a mean age of 61.5 (± SD 16.1) years.</div><div>In RHD, the lymphatic vessel size and count per mm² were increased compared to the degenerative valves. Statistical significance was found in the blood and lymphatic vessel size, and lymphatic vessel count. In RHD, the combined blood and lymphatic vessel size increased from 1.45µm² (± SD 2.52) to 4.91 µm² (± SD 6.33). The lymphatic vessel count was 1,123.86 per mm² (± SD 2,154.68) in the RHD and 213.08 per mm² (± SD 390.13) in the myxomatous degenerative valves. Angiogenesis and lymphangiogenesis characterize mitral valves in RHD.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"78 ","pages":"Article 107744"},"PeriodicalIF":2.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191550","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}

{"title":"Molecular features and cell composition of left-dominant arrhythmogenic cardiomyopathy reveals key pathways and therapeutic targets","authors":"Yiqi Zhao ,&nbsp;Mengda Xu ,&nbsp;Xiumeng Hua ,&nbsp;Yuan Chang ,&nbsp;Yixuan Sheng ,&nbsp;Dan Shan ,&nbsp;Ningning Zhang ,&nbsp;Xiao Chen ,&nbsp;Jiangping Song","doi":"10.1016/j.carpath.2025.107743","DOIUrl":"10.1016/j.carpath.2025.107743","url":null,"abstract":"<div><h3>Background</h3><div>Arrhythmogenic cardiomyopathy (ACM) is a myocardial disorder characterized by arrhythmias and an increased risk of sudden cardiac death, particularly in left-dominant arrhythmogenic cardiomyopathy (LACM), which primarily affects the left ventricle. This study aims to elucidate the cellular and molecular mechanisms underlying LACM by performing an in-depth single-nucleus RNA sequencing (snRNA-seq) analysis to identify key transcriptional signatures and pathways involved in the disease's pathogenesis.</div></div><div><h3>Method</h3><div>Human heart samples were collected from five patients undergoing heart transplantation due to ACM and from four healthy donors. Single nuclei were isolated from myocardial tissues and subjected to snRNA-seq using the 10 × Genomics Chromium platform. Data were processed and analyzed to identify distinct cell populations and their differentially expressed genes. Immunofluorescence staining was used to validate key findings.</div></div><div><h3>Result</h3><div>The snRNA-seq analysis revealed an increased proportion of fibroblasts and adipocytes in the left ventricles of LACM patients, suggesting a cellular basis for the fibrofatty remodeling observed in the disease. Key cell populations, including cardiomyocytes (CMs), fibroblasts (Fbs), and adipocytes (Adipo), were identified with distinct transcriptional profiles. We identified a disease-associated cardiomyocyte subpopulation (CM1) characterized by upregulation of fibrosis-, metabolism-, and stress-related markers, indicating transcriptional remodeling processes involved in LACM. The Fb subgroup Fb1 was characterized by genes involved in the PI3K-AKT signaling pathway. Adipocyte subpopulations exhibited gene expression features reflecting adaptation to the cardiac pathological environment, including markers associated with extracellular matrix remodeling and metabolic stress.</div><div>Immunofluorescence staining validated the high expression of key markers of LACM patients.</div></div><div><h3>Conclusion</h3><div>This study provides a cellular and molecular characterization of LACM, identifying key pathways and transcriptional signatures that contribute to the disease's pathogenesis. These findings enhance our understanding of LACM and offer potential targets for therapeutic intervention.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"78 ","pages":"Article 107743"},"PeriodicalIF":2.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092902","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}

{"title":"COVER 3: Editorial Board","authors":"","doi":"10.1016/S1054-8807(25)00025-0","DOIUrl":"10.1016/S1054-8807(25)00025-0","url":null,"abstract":"","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"77 ","pages":"Article 107740"},"PeriodicalIF":2.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947343","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}

{"title":"COVER 4: Table of Contents/Barcode PMS 200","authors":"","doi":"10.1016/S1054-8807(25)00026-2","DOIUrl":"10.1016/S1054-8807(25)00026-2","url":null,"abstract":"","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"77 ","pages":"Article 107741"},"PeriodicalIF":2.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947344","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}