Newer indications for permanent pacemakers.

The role of pacemakers in cardiac disease continues to expand, and recent technology has allowed therapy to be individualized. Newer indications for pacemakers now include long QT syndrome, neurocardiogenic syncope, hypertrophic obstructive cardiomyopathy, and drug refractory atrial fibrillation.

Asthma and the risk of cardiac events in the Long QT syndrome. Long QT Syndrome Investigative Group.

While acquiring data for the International Long QT Syndrome Registry, we noticed that a number of patients referred for long QT syndrome (LQTS) were affected by asthma. The effect of asthma comorbidity on clinical course of LQTS has not been studied. This study aimed to evaluate the prevalence of asthma in patients with LQTS, determine the influence of asthma comorbidity on outcome of LQTS patients, and to investigate the confounding effects of beta mimetics and beta blockers on the occurrence of cardiac events in asthmatic patients. The influence of asthma on risk of cardiac events (syncope, aborted cardiac arrest, or LQTS death) was evaluated after accounting for age, gender, QTc, and RR interval duration, beta-blocker and beta-mimetic use. Asthma was identified in 226 (5.2%) of 4,310 studied LQTS family members. Longer QTc duration was associated with higher incidence of asthma (p <0.001). Asthma was independently associated with significantly increased risk of cardiac events in affected LQTS patients (hazard ratio 1.32; p = 0.048) and in borderline-affected family members (hazard ratio 2.08; p = 0.004) after adjustment for QTc, RR interval, and gender. An increased risk of cardiac events in asthmatic patients observed before beta-blocker therapy was reduced after initiation of treatment with beta blockers. In conclusion, the occurrence of asthma in LQTS patients increases with QTc duration. Asthma comorbidity in LQTS patients is associated with an increased risk of cardiac events. The asthma-associated increase in the risk of LQTS-related cardiac events is diminished after initiation of beta-blocker therapy, suggesting a possible role of beta-receptor modulation underlying asthma-LQTS association.

Electrocardiographic findings in patients with diphenhydramine overdose.

QT interval prolongation and torsades de pointes ventricular tachycardia have been reported after therapeutic doses and overdosage of second generation antihistamines, such terfenadine and astemizol. Diphenhydramine (DPHM), a first generation H1 antagonist, is the most frequently used antihistaminic drug. Despite its widespread use, there are no data about cardiac action and electrocardiographic consequences of DPHM overdose. The 12-lead electrocardiograms of 126 patients (mean age 26 +/- 11 years) who had DPHM overdose were evaluated. The ingestion of large doses of DPHM (in majority of cases the dose was >500 mg) was primarily suicidal. Repolarization duration, dispersion, and morphology were evaluated in DPHM overdose patients and compared with those of healthy subjects. Mean heart rate of DPHM overdose patients was 103 +/- 25 beats/min. The QTc duration was significantly longer (453 +/- 43 vs 416 +/- 35 ms, respectively, p <0.001) and mean T-wave amplitude significantly lower (0.20 +/- 0.10 vs 0.33 +/- 0.15 mV, respectively, p <0.001) in DPHM-overdose patients than in control subjects. Dispersion of repolarization was significantly lower in DPHM-overdose patients than in control subjects (42 +/- 25 vs 52 +/- 21 ms, respectively; p = 0.003). None of the DPHM-overdose patients experienced torsades de pointes. In conclusion, DPHM overdose is associated with a significant increase in heart rate and a significant but moderate QTc prolongation. None of the studied patients, including those who had apparent QTc prolongation, experienced torsades de pointes ventricular tachycardia.

Lidocaine block of LQT-3 mutant human Na+ channels.

In transiently transfected mammalian cells we have identified pharmacological consequences of a naturally occurring deletion mutation, delta KPQ, of the human heart Na+ channel alpha subunit that previously has been linked to one form of the long QT syndrome, an inherited heart disease. Our results show that the Class IB antiarrhythmic agent lidocaine blocks maintained inward current through and slows recovery from inactivation of delta KPQ-encoded Na+ channels. Block is greater for maintained than for peak current. Because incomplete inactivation of mutant Na+ channels is now thought to underlie the prolonged ventricular action potential, which is the phenotype of this disease, and we find that the delta KPQ mutation speeds the recovery from inactivation of drug-free mutant channels, our results provide evidence, for the first time, that clinically relevant dysfunctional properties of an ion channel can be selectively targeted on the basis of the molecular properties conferred on the channel by an inherited genetic disorder.