Short QT in a cohort of 1.7 million persons: prevalence, correlates, and prognosis.

BACKGROUND: Short QT syndrome (QTc ≤ 300 ms) is a novel hereditary channelopathy linked to syncope, paroxysmal atrial fibrillation, and sudden cardiac death. However, its epidemiological features remain unsettled. OBJECTIVES: (1) To assess the prevalence of short QT in a large population-based sample; (2) to evaluate its demographic and clinical correlates and; (3) to determine its prognosis. METHODS: A database of 6.4 million electrocardiograms (ECGs) obtained between 1995 and 2008 among 1.7 million persons was used. An internal, population-based method for heart rate correction (QTcreg ) was used and all ECGs with QTcreg ≤300 ms were manually validated. Linked health plan databases were used for covariate and survival ascertainment. RESULTS: Of 6,387,070 ECGs, 1086 had an ECG with machine-read QTcreg ≤300 ms. Only 4% (45/1086) were validated yielding a prevalence of 0.7 per 100,000 or 1 of 141,935 ECGs. At the person level, the overall prevalence of QTcreg ≤300 ms was 2.7 per 100,000 or 1 of 37,335. The factors independently and significantly associated with validated QTcreg ≤300 ms were age over 65 years, Black race, prior history of ventricular dysrhythmias, chronic obstructive pulmonary disease, ST-T abnormalities, ischemia, bigeminy pattern, and digitalis effect. After 8.3 years of median follow-up and relative to normal QTcreg , validated QTcreg ≤300 ms was associated after multivariate adjustment with a 2.6-fold (95% confidence interval [CI] = 1.9-3.7) increased risk of death. CONCLUSION: QTcreg ≤300 ms was extraordinarily rare and was associated with significant ECG abnormalities and reduced survival.

Long-term cardiovascular outcomes in survivors of Kawasaki disease.

BACKGROUND AND OBJECTIVE: Kawasaki disease (KD) may result in coronary aneurysm formation, but there is incomplete knowledge regarding its long-term effects. Our objective was to quantify the longer-term rates of adverse cardiac events in a modern North American KD cohort. METHODS: Using the Kaiser Permanente Northern California population, we performed a retrospective cohort study in patients with a history of KD versus matched patients without KD. Chart review was used to confirm the diagnosis of KD and all outcomes of interest, including acute coronary syndrome, coronary revascularization, heart failure, ventricular arrhythmia, valve disease, aortic aneurysm, and all-cause mortality. All outcomes occurring at age ≥15 years were included in the primary analysis. Outcome rates were compared between the 2 groups by using Cox proportional hazards analysis. RESULTS: The study included 546 KD patients and 2218 matched patients without KD. Seventy-nine percent of the KD patients received intravenous immunoglobulin and 5% had persistent coronary aneurysm. The average follow-up time was 14.9 years. Only 2 KD patients experienced outcomes after age 15 (0.246 events per 1000 person-years) compared with 7 events in the non-KD group (0.217 events per 1000 person-years), a nonsignificant difference (hazard ratio: 0.81; 95% confidence interval: 0.16-4.0). Within the KD subgroup, persistent coronary aneurysm predicted the occurrence of adverse events (P = .007). CONCLUSIONS: This is the largest US study of longer-term cardiac outcomes after KD and reveals a low rate of adverse cardiovascular events through age 21. Additional validation studies, including studies with longer-term follow-up, should be performed.

Validation of a population-based method to assess drug-induced alterations in the QT interval: a self-controlled crossover study.

PURPOSE: The purpose of this study was to ascertain, in the context of an integrated health care delivery system, the association between a comprehensive list of drugs known to have potential QT liability and QT prolongation or shortening. METHODS: By using a self-controlled crossover study with 59 467 subjects, we ascertained intra-individual change in log-linear regression-corrected QT (QTcreg ) during the period between 1995 and mid-2008 for 90 drugs while adjusting for age, gender, race/ethnicity, comorbid conditions, number of electrocardiograms (ECGs), and time between pre-ECG and post-ECG. The proportion of users of each drug-developing incident long QT was also estimated. RESULTS: Two drugs (nicardipine and levalbuterol) had no statistically significant intra-individual QTcreg shortening effects, 10 drugs had no statistically significant prolonging effect, and 78 (87%) of the drugs had statistically significant intra-individual mean QTcreg lengthening effects, ranging from 7.6 ms for aripiprazole to 25.2 ms for amiodarone. Three drugs were associated with mean QTcreg prolongation of 20 ms or greater: amiodarone (antiarrhythmic), terfenadine (antihistaminic), and quinidine (antiarrhythmic); whereas 11 drugs were associated with mean QTcreg prolongation of 15 ms or greater but less than 20 ms: trimipramine (tricyclic antidepressant), clomipramine (tricyclic antidepressant), disopyramide (antiarrhythmic), chlorpromazine (antipsychotic), sotalol (beta blocker), itraconazole (antifungal), phenylpropanolamine (decongestant/anorectic), fenfluramine (appetite suppressant), midodrine (antihypotensive), digoxin (cardiac glycoside/antiarrhythmic), and procainamide (antiarrhythmic). CONCLUSIONS: QT prolonging effects were common and varied in strength. Our results lend support to past Food and Drug Administration regulatory actions and support the role for ongoing surveillance of drug-induced QT prolongation.