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Prognostic Role of Myocarditis-Like Episodes and Their Treatment in Patients With Pathogenic Desmoplakin Variants

2025· article· en· W4413338008 on OpenAlexaff
Alessio Gasperetti, Steven A. Muller, Giovanni Peretto, Babken Asatryan, Alexandros Protonotarios, Mikaël Laredo, Pierre-Yves Tarlet, Petros Syrris, Richard Carrick, Brittney Murray, Crystal Tichnell, Paul J. Scheel, Marta Gigli, Sing‐Chien Yap, Kalliopi Pilichou, Cristina Basso, Kristen Medo, Max Jason, Valentina A. Rossi, Ardan M. Saguner, Fırat Duru, Dominic J. Abrams, Julia Cadrin‐Tourigny, Mattia Targetti, Maurizio Pieroni, Maddalena Graziosi, Elena Biagini, Philippe Charron, Moniek G.P.J. Cox, Michela Casella, Claudio Tondo, James S. Ware, Sanjay Prasad, Leonardo Calò, Eric D. Smith, Jodie Ingles, Harikrishna Tandri, Flavie Ader, Stacey Peters, Dominica Zentner, Jeremy Russo, Silvia Ravaro, Lia Crotti, Sven Dittmann, Eric Shulze-Bahr, Eric Carruth, Vikki A. Krysov, Victoria N. Parikh, Giulio Conte, Arthur A.M. Wilde, J. Peter van Tintelen, Anneline S.J.M. te Riele, Gianfranco Sinagra, Luisa Mestroni, Matthew R.G. Taylor, Marco Merlo, Luigi Adamo, Hugh Calkins, Barbara Bauce, Elena Arbelo, Perry Elliott, Estelle Gandjbakhch, Neal K. Lakdawala, Adam Helms, Cynthia A. James, Nisha A. Gilotra

Bibliographic record

VenueCirculation · 2025
Typearticle
Languageen
FieldMedicine
TopicViral Infections and Immunology Research
Canadian institutionsMontreal Heart Institute
FundersSchweizerische HerzstiftungBaugarten StiftungJohns Hopkins UniversityNational Heart, Lung, and Blood InstituteSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungNational Science Foundation
KeywordsMedicineMyocarditisInternal medicineHazard ratioHeart failureDesmoplakinPopulationCardiologyConfidence interval

Abstract

fetched live from OpenAlex

BACKGROUND: Inflammatory, myocarditis-like episodes precede and are associated with higher risk of sustained ventricular arrhythmias and heart failure in patients with pathogenic or likely pathogenic desmoplakin (DSP) variants. Whether the recurrence and treatment of myocarditis-like episodes influence the outcomes in this population is unknown. This study aimed to assess the prognostic impact of the recurrence and treatment of myocarditis-like episodes in patients with pathogenic or likely pathogenic DSP variants. METHODS: The study was designed as an observational cohort study using all patients with pathogenic or likely pathogenic DSP variants in the DSP -ERADOS Network ( Desmopakin Specific Effort for a Rare Disease Outcome Study) enrolled at 31 institutions up until April 30, 2024. Survival from ventricular arrhythmia and heart failure end points and recurrent myocarditis-like episodes was evaluated for both first and recurrent documented myocarditis-like episodes and the impact of immunosuppressive treatment on outcomes assessed. RESULTS: A total of 1014 patients with pathogenic or likely pathogenic DSP variants (62.4% female; mean age, 40.4±17.4 years; 47.1% probands) were included. Among them, 177 individuals (17.5%) experienced ≥1 documented myocarditis-like episode, with 63 of them (35.6%) receiving immunosuppressive treatment. Immunosuppressive treatment of the first documented myocarditis-like episode was associated with reduced risk of ventricular arrhythmia and heart failure outcomes (hazard ratio, 0.18 [95% CI, 0.07–0.45]; P <0.001; and hazard ratio, 0.09 [95% CI, 0.02–0.39; P =0.001, respectively) over a median follow-up of 6.4 years (95% CI, 4.0–10.5). This risk was comparable to that of patients with no history of myocarditis-like episode but did not correlate with a reduction in recurrent episodes after completion of initial immunosuppression (hazard ratio, 0.85 [95% CI, 0.47–1.54]; P =0.599). In contrast, nonsteroidal anti-inflammatory drugs or colchicine treatment did not influence outcomes. CONCLUSIONS: Immunosuppressive treatment of myocarditis-like episodes in DSP patients was associated with improved combined ventricular arrhythmia or heart failure outcomes, supporting future prospective evaluation in DSP cohorts.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.247
Teacher spread0.238 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations27
Published2025
Admission routes1
Has abstractyes

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