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.
Cardiology Division, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA. ilan.goldenberg@heart.rochester.edu
Ilan
I
Goldenberg
James
J
Bradley
Arthur
A
Moss
Scott
S
McNitt
Slava
S
Polonsky
Jennifer L
JL
Robinson
Mark
M
Andrews
Wojciech
W
Zareba
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