Peter John Schwartz

BACKGROUND: The genes for the long QT syndrome (LQTS) linked to chromosomes 3 (LQT3) and 7 (LQT2) were identified as SCN5A, the cardiac Na+ channel gene, and as HERG, a K+ channel gene. These findings opened the possibility of attempting gene-specific control of ventricular repolarization. We tested the hypothesis that the QT interval would shorten more in LQT3 than in LQT2 patients in response to mexiletine and also in response to increases in heart rate.

METHODS AND RESULTS: Fifteen ...

CONTEXT: Major depressive disorder (MDD) occurs in 15% to 23% of patients with acute coronary syndromes and constitutes an independent risk factor for morbidity and mortality. However, no published evidence exists that antidepressant drugs are safe or efficacious in patients with unstable ischemic heart disease.

OBJECTIVE: To evaluate the safety and efficacy of sertraline treatment of MDD in patients hospitalized for acute myocardial infarction (MI) or unstable angina and free of other ...

OBJECTIVES: This substudy tested a prospective hypothesis that European Myocardial Infarct Amiodarone Trial (EMIAT) patients with depressed heart rate variability (HRV) benefit from amiodarone treatment.

BACKGROUND: The EMIAT randomized 1,486 survivors of acute myocardial infarction (MI) aged < or =75 years with left ventricular ejection fraction (LVEF) < or =40% to amiodarone or placebo. Despite a reduction of arrhythmic mortality on amiodarone, all-cause mortality was not ...

BACKGROUND: Experimental evidence suggests that autonomic markers such as heart-rate variability and baroreflex sensitivity (BRS) may contribute to postinfarction risk stratification. There are clinical data to support this concept for heart-rate variability. The main objective of the ATRAMI study was to provide prospective data on the additional and independent prognostic value for cardiac mortality of heart-rate variability and BRS in patients after myocardial infarction in whom ...

OBJECTIVES: We aimed to determine whether long QT syndrome (LQTS) genotype has a differential effect on clinical course of disease in male and female children and adults after adjustment for QTc duration.

BACKGROUND: Genotype influences clinical course of the LQTS; however, data on the effect of age and gender on this association are limited.

METHODS: The LQTS genotype, QTc duration, and follow-up were determined in 243 cases of LQTS caused by the KCNQ1 potassium channel gene mutations ...

BACKGROUND: Ventricular arrhythmias are a major cause of death after myocardial infarction, especially in patients with poor left-ventricular function. Previous attempts to identify and suppress arrhythmias with various antiarrhythmic drugs failed to reduce or actually increase mortality. Amiodarone is a powerful antiarrhythmic drug with several potentially beneficial actions, and has shown benefit in several small-scale studies. We postulated that this drug might reduce mortality in ...

BACKGROUND: Heart rate (HR) variability is a marker of tonic cardiac autonomic activity and contributes in assessing risk for sudden death after myocardial infarction. Recent clinical observations have indicated that attenuation of HR variability, which occurs after myocardial infarction, may be transient. This study addresses the issue of whether autonomic control of heart rate recovers at different rates after myocardial infarction in subjects at high and low risk for ventricular ...

BACKGROUND: J-wave syndromes have emerged conceptually to encompass the pleiotropic expression of J-point abnormalities including Brugada syndrome (BrS) and early repolarization syndrome (ERS). KCNJ8, which encodes the cardiac K(ATP) Kir6.1 channel, recently has been implicated in ERS following identification of the functionally uncharacterized missense mutation S422L.

OBJECTIVE: The purpose of this study was to further explore KCNJ8 as a novel susceptibility gene for J-wave ...

BACKGROUND: Changes in heart rate during exercise and recovery from exercise are mediated by the balance between sympathetic and vagal activity. Since alterations in the neural control of cardiac function contribute to the risk of sudden death, we tested the hypothesis that among apparently healthy persons, sudden death is more likely to occur in the presence of abnormal heart-rate profiles during exercise and recovery.

METHODS: A total of 5713 asymptomatic working men (between the ages ...

Mutations in the minK gene KCNE1 have been linked to the LQT5 variant of human long QT syndrome. MinK assembles with KvLQT1 to produce the slow delayed rectifier K+ current IKs and may assemble with HERG to modulate the rapid delayed rectifier IKr. We used electrophysiological and immunocytochemical methods to compare the cellular phenotypes of wild-type minK and four LQT5 mutants co-expressed with KvLQT1 in Xenopus oocytes and HERG in HEK293 cells. We found that three mutants, V47F, ...

We have suggested that among conscious dogs with a healed anterior wall myocardial infarction (MI) a depressed baroreflex sensitivity (BRS) carries a higher risk of developing ventricular fibrillation during a brief ischemic episode associated with an exercise stress test. The clinical and pathophysiological implications of our previous findings prompted the present study, which addressed three major questions: 1) Is, indeed, analysis of BRS after MI a specific and sensitive marker for ...

BACKGROUND: The congenital long-QT syndrome (LQTS) is an important cause of sudden cardiac death in children without structural heart disease. However, specific risk factors for life-threatening cardiac events in children with this genetic disorder have not been identified.

METHODS AND RESULTS: Cox proportional-hazards regression modeling was used to identify risk factors for aborted cardiac arrest or sudden cardiac death in 3015 LQTS children from the International LQTS Registry who ...

IMPORTANCE: Intrauterine fetal death or stillbirth occurs in approximately 1 out of every 160 pregnancies and accounts for 50% of all perinatal deaths. Postmortem evaluation fails to elucidate an underlying cause in many cases. Long QT syndrome (LQTS) may contribute to this problem.

OBJECTIVE: To determine the spectrum and prevalence of mutations in the 3 most common LQTS susceptible genes (KCNQ1, KCNH2, and SCN5A) for a cohort of unexplained cases.

DESIGN, SETTING, AND PATIENTS: In this ...

The relationship between activity of the autonomic nervous system, myocardial ischemia, and malignant arrhythmias has been investigated in a new experimental preparation for sudden death. Fifty-seven dogs were chronically instrumented and studied under control conditions (n = 15) and 1 month after production of an anterior myocardial infarction (n = 42). The protocol consisted in occluding the left circumflex coronary artery for 2 min, commencing at the last minute of an exercise stress ...

The interest for the antifibrillatory effect of vagal stimulation has been largely limited by the fact that this concept seemed restricted to acute experiments in anesthetized animals. To explore the potentially protective role of vagal stimulation in conscious animals we developed a chronically implantable device to be placed around the cervical right vagus. An anterior myocardial infarction was produced in 161 dogs; 1 month later an exercise stress test was performed on the 105 ...