The prevalence and diagnostic/prognostic utility of sinus arrhythmia in the evaluation of congenital long QT syndrome

Abstract

Background: Congenital long QT syndrome (LQTS) affects 1 in 2,500 people and can cause syncope and sudden death. Sinus arrhythmia (SA) is nonpathologic baseline respiratory variation of the RR interval.

Objective: This study sought to determine the frequency of SA and its clinical significance among patients with LQTS.

Methods: We performed an institutional review board-approved retrospective review of all patients (N = 571) evaluated in our LQTS clinic from 7/2000 to 3/2008 diagnosed with LQTS (N = 281) or dismissed as otherwise normal (N = 290). Blinded to diagnosis, the first available electrocardiogram for each patient was examined to quantitate RR interval variability.

Results: Overall, 151 of 281 patients (54%) with LQTS (159 female patients, average age 21.8 ± 16.5 years, average QTc 466 ± 43 ms) had SA with an average RR variability of 13% ± 8% compared with 201 of 290 (69%) patients dismissed as normal (178 female patients, average age 21.7 ± 16 years, average QTc 424 ± 30 ms) who demonstrated SA with RR variability of 16% ± 10% (P < .0001). These differences remained significant when patients on concurrent beta-blocker therapy were excluded (P < .001). SA was least common in LQT3 (23%) compared with LQT1 (61%, P < .005) and LQT2 (51%, P = .055). Patients presenting with torsades de pointes or aborted cardiac arrest had lower RR variability (10% ± 7%, P < .03).

Conclusion: SA frequency and magnitude of RR variability was lower among patients with LQTS compared with those patients dismissed as otherwise normal. This attenuation in RR interval variability remained when patients on beta-blocker therapy were excluded. Although the presence/absence of sinus arrhythmia is of little diagnostic value due to cohort overlap, LQTS patients with negligible RR interval variation may be at higher risk.

Figure 1

Lead II of a 12-lead electrocardiogram from 3 distinct patients from our cohort, including (A) an 8-year-old female patient who was dismissed as normal, RR variability = 39%, (B) A 4-year-old male patient with LQT1, RR variability = 14%, and (C) a 24-year-old genotype-negative female patient with a history of aborted cardiac arrest, RR variability = 7%.

Figure 2

Bar graph demonstrating (A) the frequency of sinus arrhythmia between patients dismissed as ostensibly healthy (normal subjects) and patients diagnosed with LQTS, and between the 3 most common LQTS genotypes, and (B) the RR variability (%) between the same groups. LQT = long QT syndrome; SA = sinus arrhythmia.

Figure 3

Scatter plot of baseline QTc compared with the RR variability of the entire cohort. Note the weak but significant relationship (P < .0001, r = 0.03).