Effects of β-blockers on ventricular repolarization documented by 24-hour electrocardiography in long QT syndrome type 2.

Background: Long QT syndrome (LQTS) is an inherited arrhythmia disorder characterized by ventricular repolarization abnormalities and a risk of sudden cardiac death. The electrophysiological components generating the high risk of arrhythmias in LQTS are prolonged repolarization, increased dispersion of repolarization, and early afterdepolarizations, which are clinically estimated as QT interval, T-wave peak to T-wave end (TPE) interval, and T2/T1-wave amplitude ratio, respectively. In experimental LQTS type 2 (LQT2) models, β-blockers decrease dispersion of repolarization and prevent early afterdepolarizations.

Genealogy and clinical course of catecholaminergic polymorphic ventricular tachycardia caused by the ryanodine receptor type 2 P2328S mutation.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe inherited arrhythmic disease associated with a risk of syncope and sudden cardiac death (SCD).

Aims: We aimed at identifying RYR2 P2328S founder mutation carriers and describing the clinical course associated with the mutation.

Methods: The study population was drawn from the Finnish Inherited Cardiac Disorder Research Registry, and from the present genealogical study.

Waveform prototype-based feature learning for automatic detection of the early repolarization pattern in ECG signals.

Objective: Our aim was to develop an automated detection method, for prescreening purposes, of early repolarization (ER) pattern with slur/notch configuration in electrocardiogram (ECG) signals using a waveform prototype-based feature vector for supervised classification.

Approach: The feature vectors consist of fragments of the ECG signal where the ER pattern is located, instead of abstract descriptive variables of ECG waveforms. The tested classifiers included linear discriminant analysis, k-nearest neighbor algorithm, and support vector machine (SVM).

ECG left ventricular hypertrophy as a risk predictor of sudden cardiac death.

Background: Electrocardiographic (ECG) left ventricular hypertrophy (LVH) is an established risk factor for cardiovascular events. However, limited data is available on the prognostic values of different ECG LVH criteria specifically to sudden cardiac death (SCD). Our goal was to assess relationships of different ECG LVH criteria to SCD.

Clinical and molecular genetic risk determinants in adult long QT syndrome type 1 and 2 patients : Koponen et al. Follow-up of adult LQTS patients.

Background: Long QT syndrome (LQTS) is an inherited cardiac disorder predisposing to sudden cardiac death (SCD). We studied factors affecting the clinical course of genetically confirmed patients, in particular those not receiving β-blocker treatment. In addition, an attempt was made to associate risk of events to specific types of KCNQ1 and KCNH2 mutations.

Repolarization Heterogeneity Measured With T-Wave Area Dispersion in Standard 12-Lead ECG Predicts Sudden Cardiac Death in General Population.

Background: We developed a novel electrocardiographic marker, T-wave area dispersion (TW-Ad), which measures repolarization heterogeneity by assessing interlead T-wave areas during a single cardiac cycle and tested whether it can identify patients at risk for sudden cardiac death (SCD) in the general population.

Methods And Results: TW-Ad was measured from standard digital 12-lead ECG in 5618 adults (46% men; age, 50.9±12.

The genetics underlying idiopathic ventricular fibrillation: A special role for catecholaminergic polymorphic ventricular tachycardia?

Background: Ventricular fibrillation (VF) is a major cause of sudden cardiac death. In some cases clinical investigations fail to identify the underlying cause and the event is classified as idiopathic (IVF). Since mutations in arrhythmia-associated genes frequently determine arrhythmia susceptibility, screening for disease-predisposing variants could improve IVF diagnostics.

Vasomotor hot flashes and cardiac repolarization: a randomized placebo-controlled trial of postmenopausal hormone therapy.

Objective: The aim of the study was to compare the effects of different hormone therapies on cardiac repolarization in recently postmenopausal women with and without hot flashes.

Methods: We recruited 150 healthy women: 72 with and 78 without hot flashes. They were randomized and treated for 6 months with transdermal estradiol (1 mg/day), oral estradiol (OE) alone (2 mg/day) or combined with medroxyprogesterone acetate (MPA; 5 mg/day), or placebo.

Slowed depolarization and irregular repolarization in catecholaminergic polymorphic ventricular tachycardia: a study from cellular Ca2+ transients and action potentials to clinical monophasic action potentials and electrocardiography.

Aims: Spontaneous Ca release leads to afterdepolarizations and triggered arrhythmia in catecholaminergic polymorphic ventricular tachycardia (CPVT). Irregular Ca release is hypothesized to manifest as slowed depolarization and irregular repolarization. Our goal was to study depolarization and repolarization abnormalities in CPVT, as they remain largely uninvestigated.

Prediction of sudden cardiac death with automated high-throughput analysis of heterogeneity in standard resting 12-lead electrocardiograms.

Background: Heterogeneity of depolarization and repolarization underlies the development of lethal arrhythmias.

Objective: We investigated whether quantification of spatial depolarization and repolarization heterogeneity identifies individuals at risk for sudden cardiac death (SCD).

Methods: Spatial R-, J-, and T-wave heterogeneity (RWH, JWH, and TWH, respectively) was analyzed using automated second central moment analysis of standard digital 12-lead electrocardiograms in 5618 adults (2588, 46% men; mean ± SEM age 50.

Cardiac repolarization in recently postmenopausal women with or without hot flushes.

Objective: Menopausal hot flushes are associated with elevated activity of the sympathetic nervous system and may be related to increased risk for cardiovascular events. Sympathetic activation may trigger severe arrhythmias by modulating cardiac repolarization. The aim of this study was to evaluate the impact of hot flushes on cardiac repolarization in postmenopausal women with and without hot flushes.

Follow-up of 316 molecularly defined pediatric long-QT syndrome patients: clinical course, treatments, and side effects.

Background: Inherited long-QT syndrome (LQTS) is associated with risk of sudden death. We assessed the clinical course and the fulfillment of current treatment strategies in molecularly defined pediatric LQTS type 1 and (LQT1) and type 2 (LQT2) patients.

Methods And Results: Follow-up data covering a mean of 12 years were collected for 316 genotyped LQT1 and LQT2 patients aged 0 to 18 years.

Sensitivity and specificity of automated detection of early repolarization in standard 12-lead electrocardiography.

Background: Early repolarization (ER) is defined as an elevation of the QRS-ST junction in at least two inferior or lateral leads of the standard 12-lead electrocardiogram (ECG). Our purpose was to create an algorithm for the automated detection and classification of ER.

Methods: A total of 6,047 electrocardiograms were manually graded for ER by two experienced readers.

Differences in ST-elevation and T-wave amplitudes do not reliably differentiate takotsubo cardiomyopathy from acute anterior myocardial infarction.

Background: Previous efforts to distinguish acute anterior ST-elevation myocardial infarction (anterior-STEMI) from various forms of takotsubo cardiomyopathy (TTC) by electrocardiography (ECG) have produced differing results.

Methods: We performed a retrospective comparison of acute ECGs between 48 apical and 9 mid-ventricular TTC patients, with 96 anterior-STEMI patients. ECG was recorded in acute phase (<24h from onset of pain), and analyzed for ST-changes, negative T-waves, abnormal Q-waves and QT-interval duration.

Predictive value of electrocardiographic T-wave morphology parameters and T-wave peak to T-wave end interval for sudden cardiac death in the general population.

Background: Previous population studies have found an association between electrocardiographic T-wave morphology parameters and cardiovascular mortality, but their relationship to sudden cardiac death (SCD) is not clear. To our knowledge, there are no follow-up studies assessing the association between electrocardiographic T-wave peak to T-wave end interval (TPE) and SCD. We assessed the predictive value of electrocardiographic T-wave morphology parameters and TPE for SCD in an adult general population sample.

Cell model of catecholaminergic polymorphic ventricular tachycardia reveals early and delayed afterdepolarizations.

Background: Induced pluripotent stem cells (iPSC) provide means to study the pathophysiology of genetic disorders. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a malignant inherited ion channel disorder predominantly caused by mutations in the cardiac ryanodine receptor (RyR2). In this study the cellular characteristics of CPVT are investigated and whether the electrophysiological features of this mutation can be mimicked using iPSC -derived cardiomyocytes (CM).

T-wave morphology after epinephrine bolus may reveal silent long QT syndrome mutation carriers.

Background: Long QT syndrome (LQTS) gene mutation carriers with indeterminate electrocardiogram frequently escape clinical diagnosis. We assessed the use of epinephrine bolus injection in revealing T-wave abnormalities.

Methods: We recruited 30 genotyped asymptomatic LQTS gene carriers with nondiagnostic QT interval and 15 controls.

A common variant near the KCNJ2 gene is associated with T-peak to T-end interval.

Background: T-peak to T-end (TPE) interval on the electrocardiogram is a measure of myocardial dispersion of repolarization and is associated with an increased risk of ventricular arrhythmias. The genetic factors affecting the TPE interval are largely unknown.

Objective: To identify common genetic variants that affect the duration of the TPE interval in the general population.

Vasomotor hot flashes and heart rate variability: a placebo-controlled trial of postmenopausal hormone therapy.

Objective: The aim of the study was to compare the responses of heart rate variability (HRV) with hormone therapy in recently postmenopausal women with and without vasomotor hot flashes.

Methods: Seventy-two women with and 78 women without hot flashes were randomized to receive transdermal estradiol gel (1 g/day), oral estradiol alone (2 mg/day), oral estradiol combined with medroxyprogesterone acetate (MPA; 5 mg/day), or placebo for 6 months. Time- and frequency-domain measures of HRV were assessed using 24-hour electrocardiographic recordings at baseline and after hormone therapy.

Epinephrine bolus test in detecting long QT syndrome mutation carriers with indeterminable electrocardiographic phenotype.

Background: In long QT syndrome (LQTS), prolonged and heterogeneous ventricular repolarization predisposes to serious arrhythmias. We examined how QT intervals are modified by epinephrine bolus in mutation carriers of three major LQTS subtypes with indefinite QT interval.

Methods: Genotyped, asymptomatic subjects with LQTS type 1 (LQT1; n = 10; four different KCNQ1 mutations), type 2 (LQT2; n = 10; three different HERG mutations), and type 3 (LQT3; n = 10; four different SCN5A mutations), and healthy volunteers (n = 15) were examined.

Serial assessment of the electrocardiographic strain pattern for prediction of new-onset heart failure during antihypertensive treatment: the LIFE study.

Aims: Although the presence of the electrocardiographic (ECG) strain pattern has been associated with an increased risk of developing heart failure (HF), the relationship of regression vs. persistence vs. development of new ECG strain to subsequent HF is unclear.

Comparison of QT peak and QT end interval responses to autonomic adaptation in asymptomatic LQT1 mutation carriers.

Background:   LQT1 subtype of long QT syndrome is characterized by defective I(Ks) , which is intrinsically stronger in the epicardium than in the midmyocardial region. Electrocardiographic QT peak and QT end intervals may reflect complete repolarization of epicardium and midmyocardial region of the ventricular wall, respectively. Repolarization abnormalities in LQT1 carriers may therefore be more easily detected in the QT peak intervals.

Dynamic QT/RR relationship in post-myocardial infarction patients with and without cardiac arrest.

Objectives: Changes in QT interval dynamicity may be associated with susceptibility to ventricular fibrillation (VF) after myocardial infarction (MI). We tested the hypothesis that dynamic QT/RR relationship might differ between post-MI patients with and without a history of VF. We also evaluated the influence of negative T-waves on the assessment of QT/RR relationship.

Abnormal repolarization dynamics revealed in exercise test in long QT syndrome mutation carriers with normal resting QT interval.

Aims: The identification of affected family members with long QT syndrome (LQTS) is often difficult due to their normal-or only marginally lengthened-QT interval duration. We examined whether physical exercise test could increase the ability to detect the mutation carrier status in phenotypically normal LQTS family members.

Methods And Results: Sixty-six subjects were included: 15 were carriers of KCNQ1 (LQT1); 15 of KCNH(2) (LQT2); and 9 of SCN5A (LQT3) gene mutations with no, or borderline, QT lengthening; and 27 were healthy controls.