Abstract：
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.
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.
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.
摘要：
背景：晚期房室传导阻滞（AVB），也就是说,高于二级Mobitz-1，是运动员的异常发现。尽管深入调查,在一些情况下，发病机制仍然未知，但仍经常植入起搏器。越来越多的证据表明，循环的抗Ro/Sjögren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AVB的流行病学相关且潜在可逆的原因。该研究的目的是确定大量年轻运动员中与抗Ro/SSA相关的高级AVB的患病率。
结果：一项横断面研究纳入了2536名年龄<40岁无心脏疾病/介入治疗史的连续运动员。进行静息和运动心电图，并通过24小时动态心电图进一步评估出现任何AVB的患者。具有二级AVB的运动员及其母亲接受了抗Ro/SSA测试。此外，使用tSA201细胞测试了来自具有抗Ro/SSA阳性和抗Ro/SSA阴性晚期AVB的受试者的纯化的免疫球蛋白G的L型钙电流和L型钙通道表达。在整个样本中，晚期AVB的全球患病率约为0.1%，但是，当选择性地考虑经过严格训练的青春期后男性受试者时，风险大大增加（2％）。虽然高级AVB的运动员都没有表现出心脏异常，在100％的病例中检测到抗Ro/SSA抗体。离体实验表明，患有晚期AVB的抗Ro/SSA阳性但非阴性受试者的免疫球蛋白G急性抑制L型钙电流并长期下调L型钙通道表达。
结论：我们的研究提供了证据，表明年轻运动员发生AVB，在大多数情况下与阻断L型钙通道的抗Ro/SSA抗体相关。这些发现可能为免疫调节疗法开辟新的途径，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。
结果：一项横断面研究纳入了2536名年龄<40岁无心脏疾病/介入治疗史的连续运动员。进行静息和运动心电图，并通过24小时动态心电图进一步评估出现任何AVB的患者。具有二级AVB的运动员及其母亲接受了抗Ro/SSA测试。此外，使用tSA201细胞测试了来自具有抗Ro/SSA阳性和抗Ro/SSA阴性晚期AVB的受试者的纯化的免疫球蛋白G的L型钙电流和L型钙通道表达。在整个样本中，晚期AVB的全球患病率约为0.1%，但是，当选择性地考虑经过严格训练的青春期后男性受试者时，风险大大增加（2％）。虽然高级AVB的运动员都没有表现出心脏异常，在100％的病例中检测到抗Ro/SSA抗体。离体实验表明，患有晚期AVB的抗Ro/SSA阳性但非阴性受试者的免疫球蛋白G急性抑制L型钙电流并长期下调L型钙通道表达。
结论：我们的研究提供了证据，表明年轻运动员发生AVB，在大多数情况下与阻断L型钙通道的抗Ro/SSA抗体相关。这些发现可能为免疫调节疗法开辟新的途径，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。
