Background/Purpose: Severe brady-arrhythmias [complete atrioventricular block (cAVB) and sick sinus syndrome (SSS)] have a prevalence of 0.04% and 0.8% in the general population respectively and are sparsely reported in systemic lupus erythematosus (SLE). Immune-mediated damage to the conduction system and atherosclerosis represent the most important risk factors. However, several case reports raised the possibility that antimalarials (AM) may play a role. The aim of the present study is to analyze the characteristics and associated factors of such arrhythmias in a defined lupus cohort.

Methods: The database of a large lupus clinic was searched for patients who received a permanent pacemaker (PPM) from 2000 to December 2016. Demographic, clinical, immunological and therapeutic data along with electrocardiographic (ECG) and echocardiographic (ECHO) variables were analyzed (based on the last available ECG and ECHO, respectively). Patients with a PPM due to brady-arrhythmias (cases) were compared with age-, sex- and disease duration-matched (±5 years) patients without a PPM (controls, 1:2 ratio). Statistical analysis was performed with SAS 9.0; p<0.05 was considered significant.

Results: Out of 1366 patients, 18 (14 females) received a PPM, 13 with cAVB (prevalence 0.95%) and 5 with SSS (0.37%). Six patients (33.3%) had coronary artery disease (CAD) whereas four (22.2%) had cardiac surgery shortly before PPM implantation. Seven patients (38.9%) did not have any risk factors (coronary angiography at the time of PPM implantation was normal in all of them, no prior structural heart disease). Six of these 7 patients developed ocular toxicity due to chronic AM treatment (all were taking AM for 22.6 years on average) shortly before or after PPM. One patient received a PPM two years after renal transplantation. A comparison between cases and controls for associated factors is shown in Table 1.

Significant differences in ECG variables included 1^st degree AVB [16.7% vs. 0%, p=0.02], right bundle branch block [55.6% vs. 3.3%, p<0.001] and left anterior fascicular block [44.4% vs. 0%, p<0.001]. ECHO variables revealed a significant difference in the prevalence of septal hypertrophy [46.7% vs. 25%, p=0.014]. Multi-variate analysis revealed that prolonged AM treatment was the only independent factor associated with the development of such arrhythmias [OR=1.15, 95%CI=1.01-1.31, p=0.035].

Conclusion: The prevalence of cAVB in SLE was approximately 24-fold that of the general population. Prolonged AM treatment increases the risk for severe brady-arrhythmias and may be considered as their cause in the absence of other risk factors. Certain ECG characteristics (RBBB, LAFB) may represent indicators of an ongoing damage in the conduction system and should be monitored in such patients.