Beta-blocker efficacy in high-risk patients with the congenital long-QT syndrome types 1 and 2: implications for patient management.
BACKGROUND
Beta-blockers are the mainstay therapy in patients with the congenital long-QT syndrome (LQTS) types 1 and 2. However, limited data exist regarding the efficacy and limitations of this form of medical management within high-risk subsets of these populations.


RESULTS
Multivariate analysis was carried out to identify age-related gender- and genotype-specific risk factors for cardiac events (comprising syncope, aborted cardiac arrest [ACA] or sudden cardiac death [SCD]) from birth through age 40 years among 971 LQT1 (n = 549) and LQT2 (n = 422) patients from the International LQTS Registry. Risk factors for cardiac events included the LQT1 genotype (HR = 1.49, P = 0.003) and male gender (HR = 1.31, P = 0.04) in the 0-14 years age group; and the LQT2 genotype (HR = 1.67, P < 0.001) and female gender (HR = 2.58, P < 0.001) in the 15-40 years age group. Gender-genotype subset analysis showed enhanced risk among LQT1 males (HR = 1.93, P < 0.001) and LQT2 females (HR = 3.28, P < 0.001) in the 2 respective age groups. Beta-blocker therapy was associated with a significant risk-reduction in high-risk patients, including a 67% reduction (P = 0.02) in LQT1 males and a 71% reduction (P < 0.001) in LQT2 females. Life-threatening events (ACA/SCD) rarely occurred as a presenting symptom among beta-blocker-treated patients. However, high-risk patients who experienced syncope during beta-blocker therapy had a relatively high rate of subsequent ACA/SCD (>1 event per 100 patient-years).


CONCLUSIONS
The present findings suggest that beta-blocker therapy should be routinely administered to all high-risk LQT1 and LQT2 patients without contraindications as a first line measure, whereas primary defibrillator therapy should be recommended for those who experience syncope during medical therapy.
Goldenberg
Ilan
I
Cardiology Division, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA. ilan.goldenberg@heart.rochester.edu
Bradley
James
J
Moss
Arthur
A
McNitt
Scott
S
Polonsky
Slava
S
Robinson
Jennifer L
JL
Andrews
Mark
M
Zareba
Wojciech
W
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D002304:Cardiac Pacing, Artificial; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control*; D017147:Defibrillators, Implantable; D004554:Electric Countershock / Q000295:instrumentation; D005260:Female; D005838:Genotype; D006323:Heart Arrest / Q000235:genetics / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D010641:Phenotype; D016016:Proportional Hazards Models; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D029597:Romano-Ward Syndrome / Q000188:drug therapy / Q000235:genetics; D013575:Syncope / Q000209:etiology / Q000517:prevention & control; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000319:Adrenergic beta-Antagonists