Human essential hypertension: no significant association of polygenic risk scores with antihypertensive drug responses.

Polygenic risk scores (PRSs) for essential hypertension, calculated from > 900 genomic loci, were recently found to explain a significant fraction of hypertension heritability and complications. To investigate whether variation of hypertension PRS also captures variation of antihypertensive drug responsiveness, we calculated two different PRSs for both systolic and diastolic blood pressure: one based on the top 793 independent hypertension-associated single nucleotide polymorphisms and another based on over 1 million genome-wide variants. Using our pharmacogenomic GENRES study comprising four different antihypertensive monotherapies (n ~ 200 for all drugs), we identified a weak, but (after Bonferroni correction) statistically nonsignificant association of higher genome-wide PRSs with weaker response to a diuretic.

Effect of four classes of antihypertensive drugs on cardiac repolarization heterogeneity: A double-blind rotational study.

Background: T-wave area dispersion (TW-Ad) is a novel electrocardiographic (ECG) repolarization marker associated with sudden cardiac death. However, limited data is available on the clinical correlates of TW-Ad. In addition, there are no previous studies on cardiovascular drug effects on TW-Ad.

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.

Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients.

Background: Reduced nocturnal fall (non-dipping) of blood pressure (BP) is a predictor of cardiovascular target organ damage. No genome-wide association studies (GWAS) on BP dipping have been previously reported.

Methods: To study genetic variation affecting BP dipping, we conducted a GWAS in Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (n = 204) using the mean night-to-day BP ratio from up to four ambulatory BP recordings conducted on placebo.

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.

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.

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.

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization.

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.

A meta-analysis of genome-wide association studies of the electrocardiographic early repolarization pattern.

Background: The early repolarization pattern (ERP) is common and associated with risk of sudden cardiac death. ERP is heritable, and mutations have been described in syndromatic cases.

Objective: To conduct a meta-analysis of genome-wide association studies to identify common genetic variants influencing ERP.

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.

The early repolarization pattern in the general population: clinical correlates and heritability.

Objectives: This study sought to describe the clinical correlates and heritability of the early repolarization pattern (ERP) in 2 large, population-based cohorts.

Background: There is growing recognition that ERP is associated with adverse outcomes.

Methods: Participants of the Framingham Heart Study (FHS) (N = 3,995) and the Health 2000 Survey (H2K) (N = 5,489) were included.

Common genetic variants, QT interval, and sudden cardiac death in a Finnish population-based study.

Background: Although sudden cardiac death (SCD) is heritable, its genetic underpinnings are poorly characterized. The QT interval appears to have a graded relationship to SCD, and 35% to 45% of its variation is heritable. We examined the relationship among recently reported common genetic variants, QT interval, and SCD.

Population-prevalent desmosomal mutations predisposing to arrhythmogenic right ventricular cardiomyopathy.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive myocardial disorder caused by mutations of desmosomal cell adhesion proteins. The prevalence of these variants in the general population is unknown.

Objective: This study examined the spectrum and population prevalence of desmosomal mutations predisposing to ARVC in Finland.

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.

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.

Relationship of left atrial enlargement to persistence or development of ECG left ventricular hypertrophy in hypertensive patients: implications for the development of new atrial fibrillation.

Background: Persistence and development of ECG left ventricular hypertrophy (LVH) by Cornell product criteria are associated with an increased risk of atrial fibrillation compared with regression or continued absence of LVH. We postulated that this association might be in part mediated via greater left atrial enlargement (LAE) in patients with new and persistent ECG LVH.

Methods And Results: Baseline and third year ECG LVH and left atrial systolic diameter were examined in 663 patients in the Losartan Intervention For Endpoint reduction in hypertension echocardiographic substudy who were in sinus rhythm at baseline and had no history of atrial fibrillation.

Relationship of common candidate gene variants to electrocardiographic T-wave peak to T-wave end interval and T-wave morphology parameters.

Background: Single-nucleotide polymorphisms (SNPs) in genes encoding cardiac ion channels and nitric oxide synthase-1 adaptor protein (NOS1AP) are associated with electrocardiographic (ECG) QT-interval duration, but the association of these SNPs with new, prognostically important ECG measures of ventricular repolarization is unknown.

Objective: The purpose of this study was to examine the relationship of SNPs to ECG T-wave peak to T-wave end (TPE) interval and T-wave morphology parameters.

Methods: We studied 5,890 adults attending the Health 2000 Study, a Finnish epidemiologic survey.

Short-term implantation-related complications of cardiac rhythm management device therapy: a retrospective single-centre 1-year survey.

Aims: The aim of this study was to evaluate the current short-term (<3 months) complication rate related to cardiac rhythm management (CRM) device implantations.

Methods And Results: We analysed data of the complications related to all CRM device implantations during 1 year (2006) in a tertiary referral university hospital. In 567 device implantations, pacing system upgrade procedures, or lead revisions, 78 complications occurred in 69 (12.

QRS duration predicts sudden cardiac death in hypertensive patients undergoing intensive medical therapy: the LIFE study.

Aims: To determine whether QRS duration predicts sudden cardiac death (SCD) in patients with left ventricular hypertrophy and treated hypertension.

Methods And Results: Over 4.8 +/- 0.

Predictive value of electrocardiographic QT interval and T-wave morphology parameters for all-cause and cardiovascular mortality in a general population sample.

Background: The predictive value of ECG QT interval for mortality in the general population has been weak. Only a few population studies on the predictive value of ECG T-wave morphology parameters for mortality have been reported.

Objective: The purpose of this study was to examine the predictive value of ECG QT interval and T-wave morphology parameters for all-cause and cardiovascular mortality in the general population.

Prognostic value of changes in the electrocardiographic strain pattern during antihypertensive treatment: the Losartan Intervention for End-Point Reduction in Hypertension Study (LIFE).

Background: The presence of the ECG strain pattern of lateral ST depression and T-wave inversion at baseline has been associated with an increased risk of cardiovascular morbidity and mortality; however, the independent predictive value for cardiovascular outcomes of regression versus persistence versus development of new ECG strain during antihypertensive therapy is unclear.

Methods And Results: ECG strain was evaluated at baseline and after 1 year of therapy in 7409 hypertensive patients in the LIFE study (Losartan Intervention For End-point reduction in hypertension) treated in a blinded manner with atenolol- or losartan-based regimens. During 3.

High prevalence of four long QT syndrome founder mutations in the Finnish population.

Aims: Long QT syndrome (LQTS) is an inherited arrhythmia disorder with an estimated prevalence of 0.01%-0.05%.