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Heart failure and cardiomyopathies
Original research
Coexistence of cardiac sarcoidosis and arrhythmogenic cardiomyopathy-associated genetic variants: a multicentre case-control study
  1. Valentina Alice Rossi1,2,
  2. Matteo Palazzini3,
  3. Enrico Ammirati3,4,
  4. Alessio Gasperetti5,6,
  5. Martin Grubler7,8,9,
  6. Corinna Brunckhorst1,
  7. Robert Manka1,10,
  8. Andreas Giannopoulos11,
  9. Felix C Tanner1,
  10. Argelia Medeiros-Domingo12,
  11. Piero Gentile3,4,
  12. Manuela Bramerio13,
  13. Dörthe Schmidt1,
  14. Claudio Tondo6,14,
  15. Andreas J Flammer1,2,
  16. Frank Ruschitzka1,2,
  17. Firat Duru1,2,
  18. Ardan Muammer Saguner1,2
  1. 1Department of Cardiology, University Hospital Zurich, Zurich, Switzerland
  2. 2Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of Zurich, Schlieren, Switzerland
  3. 3De Gasperis Cardio Center, Niguarda Hospital, Milan, Italy
  4. 4School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
  5. 5Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
  6. 6Department of Clinical Electrophysiology and Cardiac Pacing, Centro Cardiologico Monzino, IRCCS, Milan, Italy
  7. 7Department of Internal Medicine with Cardiology, Nephrology and Intensive Care Medicine, Universitaetsklinikum Wiener Neustadt, Wiener Neustadt, Austria
  8. 8Medical Faculty, Sigmund Freud University, Vienna, Austria
  9. 9Department of Medicine, Faculty of Medicine and Dentistry, Danube Private University, Krems, Austria
  10. 10Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland
  11. 11Department of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland
  12. 12SwissDNALysis, Duebendorf, Switzerland
  13. 13Pathology Unit, Ospedale Grande Metropolitano Niguarda, Milan, Italy
  14. 14Department of Biomedical, Surgery and Dental Sciences, University of Milan, Milan, Italy
  1. Correspondence to PD Dr. med. Ardan Muammer Saguner; ardansaguner{at}gmail.com; Dr Valentina Alice Rossi; valereds{at}gmail.com

Abstract

Background Cardiac sarcoidosis (CS) is a chronic inflammatory disease characterised by non-caseating granulomas, while arrhythmogenic cardiomyopathy (ACM) is a genetic condition mainly affecting desmosomal proteins. The coexistence of CS and genetic variants associated with ACM is not well understood, creating challenges in diagnosis and management. This study aimed to describe the clinical, imaging and genetic features of patients with both conditions.

Methods This was a multicentre retrospective case-control study involving three groups of patients: those with biopsy-proven CS and pathogenic or likely pathogenic genetic variants linked to ACM (n=5); patients with genetic variants but no CS (n=5); and patients with CS without genetic variants (n=5). Clinical data, including symptoms, electrocardiographic findings and imaging results from echocardiography, cardiac magnetic resonance and positron-emission tomography, were analysed.

Results Patients with CS and genetic variants were more likely to exhibit atrioventricular block (100%), PR prolongation (204 ms vs 160 ms) and paroxysmal atrial fibrillation (80%) compared with those with genetic variants alone (0% for both). Imaging findings showed a higher prevalence of septal involvement in patients with both conditions (80%) than in those with genetic variants alone (20%). No significant differences were observed between patients with CS and genetic variants and those with CS without genetic variants. The genetic variants identified included variants in PKP2 (40%), DSG2 (20%), DSP (20%) and TTN (20%).

Conclusions The coexistence of CS and ACM-associated genetic variants is associated with distinct clinical features, including PR prolongation, AVB1°, septal involvement and paroxysmal atrial fibrillation. These findings emphasise the need to evaluate for CS in individuals with ACM and associated genetic variants who present with conduction abnormalities or septal involvement, guiding tailored diagnostic and therapeutic strategies.

  • Cardiomyopathies
  • Myocarditis
  • Cardiomyopathy, Dilated
  • Arrhythmogenic Right Ventricular Dysplasia

Data availability statement

Data are available upon reasonable request.

https://doi.org/10.1136/heartjnl-2024-324525

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    Data availability statement

    Data are available upon reasonable request.

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    Footnotes

    • X @ASaguner

    • Contributors VAR: Study design and conception, data collection, analysis and interpretation of data, draft, writing. MP, AG, MG, CB, RM, AG, FCT, AMD, PG, MB, DS: Data acquisition and collection for the study, critical revision of the article. EA, AMS: Study design and conception, draft correction and writing. CT, AJF, FR, FD: Editing and critical revision of the article. All authors read and approved the final version. VAR and AMS act as guarantors.

    • Funding The Zurich ARVC Program is supported by the Georg und Bertha Schwyzer-Winiker Foundation, Baugarten Foundation, USZ Foundation (Dr. Wild Grant), Swiss Heart Foundation grant no. FF17019 and FF21073 to AMS, Swiss National Science Foundation grant No. 160327 to FD and No. 320030-228471 to AMS.VAR received a grant by the W. and L. Rutishauser foundation.

    • Competing interests AMS has received speaker/consulting fees from Bayer Healthcare, Biotronik, Medtronic, Pfizer, Stride Bio Inc. and Zoll. AJF declares fees from Abbott, Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Pierre Fabre, Pfizer, Roche, Vifor and Zoll, as well as grant support by Novartis, AstraZeneca and Berlin Heart unrelated to this article. AG is supported by research funding grants from the Promedica Foundation and Max and Sophielene Iten-Kohaut Foundation. VAR is supported by research funding grants from the Rutishauser Foundation. EA received a grant from the Italian Ministry of Health (GR-2019-12368506; principal investigator of the investigator-driven MYTHS (Myocarditis Therapy with Steroids) trial) and a grant from Italian Ministry of Health and NextGenerationEU (PNRR-MAD-2022-12376225), serves as consultant for Lexeo and served as consultant for Kiniksa, AstraZeneca and Cytokinetics. All other authors declare no conflict of interest related to this manuscript.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.