Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers.
BACKGROUND
Data on the efficacy of beta-blockers in the 3 most common genetic long QT syndrome (LQTS) loci are limited.


OBJECTIVE
To describe and assess outcome in a large systematically genotyped population of beta-blocker-treated LQTS patients.


METHODS
Consecutive LQTS-genotyped patients (n = 335) in Italy treated with beta-blockers for an average of 5 years.


METHODS
Cardiac events (syncope, ventricular tachycardia/torsades de pointes, cardiac arrest, and sudden cardiac death) while patients received beta-blocker therapy according to genotype.


RESULTS
Cardiac events among patients receiving beta-blocker therapy occurred in 19 of 187 (10%) LQT1 patients, 27 of 120 (23%) LQT2 patients, and 9 of 28 (32%) LQT3 patients (P<.001). The risk of cardiac events was higher among LQT2 (adjusted relative risk, 2.81; 95% confidence interval [CI], 1.50-5.27; P =.001) and LQT3 (adjusted relative risk, 4.00; 95% CI, 2.45-8.03; P<.001) patients than among LQT1 patients, suggesting inadequate protection from beta-blocker therapy. Other important predictors of risk were a QT interval corrected for heart rate that was more than 500 ms in patients receiving therapy (adjusted relative risk, 2.01; 95% CI, 1.16-3.51; P =.01) and occurrence of a first cardiac event before the age of 7 years (adjusted RR, 4.34; 95% CI, 2.35-8.03; P<.001).


CONCLUSIONS
Among patients with genetic LQTS treated with beta-blockers, there is a high rate of cardiac events, particularly among patients with LQT2 and LQT3 genotypes.
Priori
Silvia G
SG
Molecular Cardiology, IRCCS Fondazione Maugeri, University of Pavia, Pavia, Italy. spriori@fsm.it
Napolitano
Carlo
C
Schwartz
Peter J
PJ
Grillo
Massimiliano
M
Bloise
Raffaella
R
Ronchetti
Elena
E
Moncalvo
Cinzia
C
Tulipani
Chiara
C
Veia
Alessia
A
Bottelli
Georgia
G
Nastoli
Janni
J
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D018450:Disease Progression; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D005838:Genotype; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015221:Potassium Channels / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D015222:Sodium Channels / Q000235:genetics; D016019:Survival Analysis; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C568320:SCN5A protein, human; D015222:Sodium Channels