Department of Medical Sciences Surgery and Neurosciences, Division of Internal Medicine and Geriatrics, Electroimmunology Unit University of Siena Siena Italy.
Cardiology Intensive Therapy Unit Department of Internal Medicine Nuovo Ospedale San Giovanni di Dio Florence Italy.
J Am Heart Assoc. 2024 Jun 18;13(12):e034893. doi: 10.1161/JAHA.124.034893. Epub 2024 Jun 15.
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.
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.
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.
高度房室传导阻滞（AVB），即二度 II 型以上的莫氏型房室传导阻滞，是运动员中的一种异常表现。尽管进行了深入的检查，但在某些情况下，其发病机制仍不清楚，但通常仍需要植入起搏器。越来越多的证据表明，循环抗 Ro/干燥综合征相关抗原 A（SSA）抗体与 L 型钙通道交叉反应并抑制相关电流，这是成人孤立性高度房室传导阻滞的一种具有流行病学相关性和潜在可逆转的原因。本研究的目的是在大量年轻运动员中确定与抗 Ro/SSA 相关的高度房室传导阻滞的患病率。
共纳入 2536 例年龄<40 岁且无心脏病/干预史的连续运动员进行横断面研究。进行静息和运动心电图检查，对出现任何房室传导阻滞的运动员进一步行 24 小时动态心电图检查。有二度房室传导阻滞的运动员及其母亲进行抗 Ro/SSA 检测。此外，用 tSA201 细胞对具有抗 Ro/SSA 阳性和抗 Ro/SSA 阴性高度房室传导阻滞的受试者的纯化免疫球蛋白 G 进行 L 型钙电流和 L 型钙通道表达的测试。在整个样本中，高度房室传导阻滞的全球患病率约为 0.1%，但当选择性考虑高强度训练的青春期后男性受试者时，风险显著增加（2%）。虽然没有一名高度房室传导阻滞的运动员出现心脏异常，但在 100%的病例中检测到抗 Ro/SSA 抗体。离体实验表明，来自具有高度房室传导阻滞的抗 Ro/SSA 阳性但非阴性受试者的免疫球蛋白 G 可急性抑制 L 型钙电流，并慢性下调 L 型钙通道表达。
我们的研究提供了证据表明，高度房室传导阻滞发生在年轻运动员中，在大多数情况下与阻断 L 型钙通道的抗 Ro/SSA 抗体有关。这些发现可能为免疫调节治疗开辟新途径，以降低运动员发生危及生命事件的风险，避免或延迟起搏器植入。
