Prolongation of the corrected QT interval in adult patients with anti‐Ro/SSA–positive connective tissue diseases

Abstract

Objective. Newborns of mothers positive for antiRo/SSA autoantibodies may develop a series of electrocardiographic (EKG) disturbances. Prolongation of the corrected QT (QTc) interval was recently reported in a significant proportion of children with maternally acquired anti-Ro/SSA antibodies, with a concomitant disappearance of EKG abnormalities and acquired maternal autoantibodies during the first year, suggesting a direct, reversible electrophysiologic effect of anti-Ro/ SSA antibodies on the ventricular repolarization. On this basis, we investigated whether these antibodies may also affect cardiac repolarization in anti-Ro/SSApositive adult patients with connective tissue diseases.Methods. Fifty-seven patients with connective tissue diseases were selected: 31 had anti-Ro/SSA antibodies and 26 did not (controls). In all subjects, we analyzed the QTc interval, heart rate variability, and signalaveraged high-resolution EKG recording.Results. Anti-Ro/SSA-positive patients showed a significant prolongation of the mean QTc interval compared with the controls (mean ؎ SD 445 ؎ 21 versus 419 ؎ 17 msec; P ‫؍‬ 0.000005). Eighteen of the 31 anti-Ro/SSA-positive patients (58%) and none of the 26 anti-Ro/SSA-negative patients had QTc values above the upper limit of normal (440 msec). Both groups had a reduction in heart rate variability, with a prevalence for the sympathetic nervous system and a high incidence of ventricular late potentials; these values were not significantly different between the 2 groups.Conclusion. Adult patients with anti-Ro/SSApositive connective tissue diseases showed a high prevalence of QTc interval prolongation. This feature, with the concomitant abnormalities in the autonomic tone and ventricular late excitability observed in all patients studied, suggests that anti-Ro/SSA-positive patients may have a particularly high risk of developing lifethreatening arrhythmias.Neonatal lupus is a rare syndrome related to the transplacental passage of autoantibodies from mothers positive for anti-Ro/SSA (and anti-La/SSB) to their newborns. These mothers frequently have autoimmune disorders, especially connective tissue diseases; however, they are sometimes entirely asymptomatic. The main feature of neonatal lupus is congenital heart block (CHB), an irreversible disturbance in cardiac conduction. Many recent studies have investigated the possible electrophysiologic and molecular mechanisms of CHB, and the findings suggest a direct arrhythmogenic activity of anti-Ro/SSA antibodies. In particular, it has been demonstrated that affinity-purified anti-Ro/SSA antibodies from mothers of children with CHB are able to induce a complete atrioventricular block in the human fetal heart as well as in a rat model of the heart, which inhibits L-type calcium currents (1).CHB is the main, but not the only, electrocardiographic abnormality associated with the transplacental passage of anti-Ro/SSA antibodies. Mazel and colleagues (2) reported sinus bradycardia in a murine model injected with IgG obtained from mothers of childr...

Clinical characteristics of lupus myocarditis in Korea

“…In chronic heart failure, intraventricular conduction is depressed and sudden cardiac death due to ventricular arrhythmia is common. Recently, there is a report that anti-Ro antibody is associated with complete heart block and corrected QT interval prolongation in adult [24]. So anti-Ro antibodies might have a role in her arrhythmia.…”

Electrocardiographic Findings in Systemic Lupus Erythematosus: Data From an International Inception Cohort

“…In patients with various types of CTD, Lazzerini and colleagues showed statistically significant prolongation of the QTc interval in anti-Ro/SSA-positive adults compared to anti-Ro/SSA-negative adults (4,5,31). Our previous single-center study, performed on a large group of SLE patients with a mean age of 44.8 years and a mean disease duration of 12.9 years, also demonstrated an association between anti-Ro/SSA antibodies and QTc interval prolongation (3).…”

“…Some evidence suggests that anti-Ro/SSA antibodies, strongly associated with congenital heart block in neonatal lupus, may also lead to QTc prolongation among adults with systemic autoimmune rheumatic diseases (3,4). In addition, the specific anti-Ro/SSA subtype (against 52-kd or 60-kd subunit) as well as its level may be important factors in determining the effect of this autoantibody on the cardiomyocytes, both in the fetus and in adults (5,6).…”

Arrhythmias Presenting in Neonatal Lupus

“…An intriguing finding has been raised by Lazzerini, who showed in a ECG-resting study that anti-Ro ⁄ SSApositive patients frequently (58% of the cases) show a QTc interval prolongation (with mean values above the upper normality limit of 440 msec) [16]. Thus, he hypothesized that anti-Ro ⁄ SSA antibodies may exert a direct arrhythmogenic effect, thereby providing patients bearing such antibodies with a high risk of developing arrhythmias, as QTc interval prolongation is a definite risk factor for arrhythmic sudden death in the general population.…”

“…QT interval prolongation has been inconsistently observed both in infants exposed to anti-Ro ⁄ SSA and in anti-Ro ⁄ SSA-positive adults [15,16]; a clear physiological basis for this possible effect is lacking at present, even if it has been hypothesized [17].…”