Anti-mitochondrial M2 Antibodies Enhance the Risk of Supraventricular Arrhythmias in Patients with Elevated Hepatobiliary Enzyme Levels

Abstract

Objective Supraventricular arrhythmias are commonly detected in patients with anti-mitochondrial antibody M2 (AMA-M2)-associated myopathy. However, the prevalence of supraventricular arrhythmias in unselected AMA-M2-positive patients and the impact of AMA-M2 on supraventricular arrhythmias have yet to be fully investigated. Methods We analyzed 384 patients (116 men; age, 60 [48-69] years), who underwent AMA-M2 testing following the detection of elevated hepatobiliary enzymes. Supraventricular arrhythmias involving atrial fibrillation, atrial flutter, atrial tachycardia, sick sinus syndrome, and atrial standstill were confirmed by a 12-lead electrocardiogram, 24-hour ambulatory monitoring, and physician-assigned diagnoses within the three years before and two years after the AMA-M2 test. Results Seventy-seven (20%) patients were positive for AMA-M2. The prevalence of supraventricular arrhythmias among AMA-M2-positive patients was higher than that among AMA-M2-negative patients (14% vs. 6%, p=0.008). A univariate analysis showed that supraventricular arrhythmias were associated with AMA-M2 positivity, aging, congestive heart failure, and the CHADS2 score. The multivariate analysis determined that AMA-M2 positivity was an independent risk factor for supraventricular arrhythmias (odds ratio 3.52, p=0.011). Among the AMA-M2-positive patients, the AMA-M2 titer did not differ to a statistically significant extent, regardless of the presence or absence of supraventricular arrhythmias. Multiple supraventricular arrhythmias with extremely low atrial deflections was a characteristic finding in AMA-M2-positive patients with supraventricular arrhythmias. Conclusion AMA-M2 enhances the risk of supraventricular arrhythmias, indicating the possible involvement of the atrial myocardium and the formation of an arrhythmogenic substrate. The results highlight the need for clinical attention to supraventricular arrhythmias in AMA-M2-positive patients.

Bench to bedside review of myositis autoantibodies

“…2 d–f). In a Japanese study, the presence of AMA-M2 in the course of IIM was associated with muscle atrophy, granuloma formation [ 173 ] and heart involvement with high risk of supraventricular arrhythmias [ 174 ]. A distinct inflammatory phenotype associated with chronic skeletal muscle disease and severe cardiac involvement was also found in a North American cohort [ 175 ].…”

Anti-mitochondrial M2 Antibodies and Myopathy: Author's Reply

“…Finsterer and Zarrouk-Mahjoub correctly pointed out, the present study is associated with several potential limitations because this observational study was retrospective in nature and because it was conducted in a single center. As we have already fully described in the main text ( 2 ), we do recognize these limitations. Unfortunately, these limitations make it difficult to supply complete answers to all of their queries within the context of the present study cohort.…”

“…The Authors Reply We would like to thank Drs. Finsterer and Zarrouk-Mahjoub ( 1 ) for their interest in our recent publication in Internal Medicine regarding the enhanced risk of supraventricular arrhythmia in patients who are positive for anti-mitochondrial M2 (AMA-M2) antibodies ( 2 ). A key statement in their letter reads, “Overall, this interesting study could be more meaningful if a prospective design would have been applied, if more clinical data would have been collected, and if patients would have been more extensively investigated for cardiac disease”.…”

Anti-mitochondrial M2 Antibodies and Myopathy

“…To the Editor We read with interest the article by Konishi et al about 77 patients with elevated anti-mitochondrial M2-antibodies (AMA-M2), 12 of whom presented with supra-ventricular arrhythmias (SVAs) ( 1 ). We have several comments and concerns on this topic.…”

“…A main disadvantage of this study is that routine surface electrocardiograms (ECGs) were available in only 45 patients and long-term ECGs in only 4 patients ( 1 ). The longer an ECG is recorded, the higher the probability that arrhythmias will be detected.…”