Advanced Atrioventricular Block in Athletes: Prevalence and Role of Anti-Ro/Sjögren Syndrome-Related Antigen A Antibodies.

Autor: Lazzerini PE; Department of Medical Sciences Surgery and Neurosciences, Division of Internal Medicine and Geriatrics, Electroimmunology Unit University of Siena Siena Italy., Bertolozzi I; Cardiology Intensive Therapy Unit Department of Internal Medicine Nuovo Ospedale San Giovanni di Dio Florence Italy.; Former Cardiology Intensive Therapy Unit, Department of Internal Medicine Hospital of Carrara Carrara Italy., Cartocci A; Department of Medical Biotechnologies University of Siena Siena Italy., Ginjupalli VKM; VA New York Harbor Healthcare System SUNY Downstate Health Sciences University New York NY USA., Teneggi PA; Center for Sports Medicine of Carrara ASL Nord-Ovest Toscana Massa-Carrara Italy., Pica D; Center for Sports Medicine of Carrara ASL Nord-Ovest Toscana Massa-Carrara Italy., Merico G; Center for Sports Medicine of Carrara ASL Nord-Ovest Toscana Massa-Carrara Italy., Bogazzi I; Emergency Department Nuovo Ospedale Apuano ASL Nord-Ovest Toscana Massa-Carrara Italy., Salvini V; Department of Medical Sciences Surgery and Neurosciences, Division of Internal Medicine and Geriatrics, Electroimmunology Unit University of Siena Siena Italy., Accioli R; Department of Medical Sciences Surgery and Neurosciences, Division of Internal Medicine and Geriatrics, Electroimmunology Unit University of Siena Siena Italy., Salvadori F; Department of Medical Sciences Surgery and Neurosciences, Division of Internal Medicine and Geriatrics, Electroimmunology Unit University of Siena Siena Italy., Marzotti T; Department of Medical Sciences Surgery and Neurosciences, Division of Internal Medicine and Geriatrics, Electroimmunology Unit University of Siena Siena Italy., Cevenini G; Department of Medical Biotechnologies University of Siena Siena Italy., Capecchi M; Department of Medical Sciences Surgery and Neurosciences, Division of Internal Medicine and Geriatrics, Electroimmunology Unit University of Siena Siena Italy., Cantara S; Department of Medical Sciences Surgery and Neurosciences, Division of Internal Medicine and Geriatrics, Electroimmunology Unit University of Siena Siena Italy.; Laboratory of Clinical and Translational Research University Hospital of Siena Siena Italy., Cantore A; Department of Medical Sciences Surgery and Neurosciences, Division of Internal Medicine and Geriatrics, Electroimmunology Unit University of Siena Siena Italy., Infantino M; Immunology and Allergology Laboratory Unit S. Giovanni di Dio Hospital Florence Italy., Bisogno S; Department of Medical Sciences Surgery and Neurosciences, Division of Internal Medicine and Geriatrics, Electroimmunology Unit University of Siena Siena Italy., Finizola F; Internal Medicine Department Sant'Antonio Abate Hospital of Fivizzano ASL Nord-Ovest Toscana Massa-Carrara Italy., D'ascenzi F; Department of Medical Biotechnologies Sports Cardiology and Rehabilitation Unit University of Siena Siena Italy., Laghi-Pasini F; Department of Medical Sciences Surgery and Neurosciences, Division of Internal Medicine and Geriatrics, Electroimmunology Unit University of Siena Siena Italy., Acampa M; Stroke Unit University Hospital of Siena Siena Italy., Capecchi PL; Department of Medical Sciences Surgery and Neurosciences, Division of Internal Medicine and Geriatrics, Electroimmunology Unit University of Siena Siena Italy., Boutjdir M; Department of Medical Biotechnologies University of Siena Siena Italy.; New York University Grossman School of Medicine New York NY USA.
Jazyk: angličtina
Zdroj: Journal of the American Heart Association [J Am Heart Assoc] 2024 Jun 18; Vol. 13 (12), pp. e034893. Date of Electronic Publication: 2024 Jun 15.
DOI: 10.1161/JAHA.124.034893
Abstrakt: Background: Advanced atrioventricular block (AVB), that is, higher than second-degree Mobitz-1, is an abnormal finding in athletes. Despite intensive investigation, in several cases the pathogenesis remains unknown, but frequently pacemaker implantation is still indicated. Increasing evidence points to circulating anti-Ro/Sjögren syndrome-related antigen A (SSA) antibodies cross-reacting with L-type calcium channel and inhibiting the related current as an epidemiologically relevant and potentially reversible cause of isolated AVB in adults. The aim of the study was to determine the prevalence of anti-Ro/SSA-associated advanced AVBs in a large sample of young athletes.
Methods and Results: A total of 2536 consecutive athletes aged <40 years without a history of cardiac diseases/interventions were enrolled in a cross-sectional study. Resting and exercise electrocardiography was performed, and those presenting any AVB were further evaluated by 24-hour Holter ECG. Athletes with second-degree AVBs and their mothers underwent anti-Ro/SSA testing. Moreover, purified immunoglobulin G from subjects with anti-Ro/SSA-positive and anti-Ro/SSA-negative advanced AVB were tested on L-type calcium current and L-type-calcium channel expression using tSA201 cells. The global prevalence of advanced AVB in the overall sample was ≈0.1%, but the risk considerably increased (2%) when intensely trained postpubertal male subjects were selectively considered. While none of the athletes with advanced AVB showed heart abnormalities, in 100% of cases anti-Ro/SSA antibodies were detected. Ex vivo experiments showed that immunoglobulin G from anti-Ro/SSA-positive but not -negative subjects with advanced AVB acutely inhibit L-type calcium current and chronically downregulate L-type-calcium channel expression.
Conclusions: Our study provides evidence that advanced AVB occurs in young athletes, in most cases associated with anti-Ro/SSA antibodies blocking L-type calcium channels. These findings may open new avenues for immunomodulating therapies to reduce the risk of life-threatening events in athletes, avoiding or delaying pacemaker implantation.
Databáze: MEDLINE
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