Author + information
- Roger Villuendas, MD†∗ (, )
- Alejandro Olivé, MD, PhD‡,
- Gladys Juncà, MD†,
- Iñaki Salvador, MD§,
- Melania Martínez-Morillo, MD‡,
- Irene Santos-Pardo, MD†,
- Damià Pereferrer, MD†,
- Elisabet Zamora, MD, PhD† and
- Antoni Bayes-Genis, MD, PhD†
- †Cardiology Service, Hospital Universitari Germans Trias i Pujol, Spain, and Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain
- ‡Rheumatology Service, Hospital Universitari Germans Trias i Pujol, Spain, and Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain
- §Immunology Service, Hospital Universitari Germans Trias i Pujol, Spain, and Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain
- ↵∗Cardiology Service, Hospital Universitari Germans Trias i Pujol, Carretera de Canyet, s/n, Badalona, Barcelona 08916, Spain
To the Editor:
Emerging evidence suggests that some autoantibodies may be involved in the pathogenesis of several heart rhythm disorders. This theory has been shown in a number of published series of patients with known autoimmune disease who often display electrocardiographic abnormalities, such as supraventricular and ventricular tachycardia, sinus bradycardia, conduction disturbances, and ventricular extrasystoles (1). However, atrioventricular (AV) conduction diseases, particularly complete (third-degree) AV block, are rarely documented (2). Recent data suggest a likely role of anti-Ro/SSA antibodies in the development of complete heart block in these patients (3). However, it is unknown what proportion of patients with complete AV block of unidentified origin may be related to a previously diagnosed autoimmune disease or may even be the first clinical manifestation of it.
In a retrospective observational study, we reviewed the data of all patients undergoing pacemaker implantation in our center (an academic tertiary hospital with a referral of 800,000 subjects) from 1987 to 2012. The study group included adults between 18 and 50 years of age at the time of pacemaker implantation as the result of AV block of unknown origin and without structural heart disease.
Of a total of 3,586 patients with pacemakers, 102 were within the pre-defined age range. After excluding 81 patients because of death (n = 12), loss to follow-up (n = 26), absence of AV block (n = 17), and presence of cardiomyopathy or a well-defined cause of AV block (n = 26 [10, myotonic dystrophy; 8, valvular disease or cardiac surgery; 3, congenital AV block; 2, iatrogenic after catheter ablation; 1, chagasic cardiomyopathy; 1, congenital heart defect; 1, myocardial infarction]), 21 patients met the inclusion criteria (0.58% of the overall pacemaker population); however, 2 of the patients refused to sign the consent form (Fig. 1). The remaining 19 patients underwent a thorough clinical assessment by expert rheumatologists and an immunological study, including antinuclear antibodies (ANAs) by indirect immunofluorescence (HEp2000, Immuno Concepts, Sacramento, California), extractable nuclear antigen antibodies by immunoblot (EUROLINE ANA- profile 3, Euroimmun, Lübeck, Germany), and quantification of anti-Ro/SSA (ELiA, Phadia, Freiburg, Germany); other specificities were tested when suggested by ANA pattern. For ANA testing, titers of 1:320 or higher were considered positive.
All patients in the study group were white; there were 13 females (68.4%), and mean age at implant was 36 ± 10 years. Mean time from pacemaker implantation to rheumatologic evaluation was 13 ± 7 years. Six patients (31.6%) had markers of immunologic disease. One had a previous diagnosis of systemic lupus erythematosus with ANA, anti-Sm, anti-RNP, anti-DNA, and anti-Ro/SSA 60 kDa antibody positivity. Five additional patients exhibited connective disease–related antibodies: 5 ANA+ (1 of them anti-Ro/SSA 52 kDa+).
Two patients (10.5%) thus had evidence of antibodies against SS-A/Ro specificities; 1 was positive for Ro/SSA 52 kDa and the other for Ro/SSA 60 kDa. Neither of the patients had a family history of rheumatic disease. In both cases, the AV block was associated with complete left bundle branch block, suggesting an involvement of the Purkinje fibers (in the Ro/SSA 52 kDa case, infra-Hisian block was documented by using intracardiac recordings). AV block was the first and isolated clinical manifestation of autoimmune disease in the Ro/SSA 52 kDa case (4).
Different autoantibodies have been involved in the etiology of varying rhythm disorders; anti-Ro/SSA is the most frequently associated with AV block. Although the presence of asymptomatic electrocardiogram abnormalities may be as high as 62% in patients with rheumatologic diseases (2), and AV conduction disorders of varying degrees have been observed in the electrocardiograms of patients with rheumatic diseases (5), the finding of severe AV conduction impairment requiring pacemaker implantation is rare (3,4). To our knowledge, only 20 patients have been reported worldwide with complete AV block and connective tissue diseases in which the anti-Ro/SSA antibody was specifically tested; the majority of these patients exhibited circulating anti-Ro/SSA positivity (16 of 20 [80%]). Cardiac symptoms preceded or were isolated with respect to other target organ involvement in only 4 of these patients. More importantly, immunosuppressive therapy was effective in 4 of the 8 patients in whom it was attempted.
The most recognized pathogenic mechanism by which anti-Ro/SSA antibodies can affect the adult conduction system is the interference with calcium channels, causing inhibition of ion currents (3). A prompt immunomodulating intervention may produce a complete recovery from a potentially life-threatening situation (3,4).
The low reporting rate of complete AV block in patients with rheumatic diseases might be due to a low incidence of this phenomenon (3). It may also be due to the lack of a more involved search for autoimmune causes in patients with unexplained AV block, including patients with no history or suspicion of autoimmune disease.
Study limitations include those of all retrospective single-center studies and the lack of information regarding deceased patients and from patients lost to follow-up. In addition, the capacity, techniques, and accuracy of diagnosing structural heart disease may have changed between 1987 and 2012. We excluded patients older than 50 years in an effort to avoid cases of idiopathic senile degeneration of the conduction system.
In summary, our data, gathered from a 25-year retrospective pacemaker series, suggest that autoimmunity should be excluded in adults with complete AV block. Performing a screening for ANA and anti-Ro/SSA antibodies could be a useful tool in the characterization of adult patients with AV block of unknown cause.
- American College of Cardiology Foundation