Continuous heart monitoring to evaluate treatment effects in pulmonary hypertension.

Background: The treatment of pulmonary hypertension (PH) has improved rapidly in recent decades. There is increasing evidence to support the role of early intervention and treatment in affecting clinical outcomes in PH.

Objectives: To assess treatment effects before and after the escalation of specific PH treatments using continuous heart monitoring with a Reveal LINQ loop recorder.

Associations between left bundle branch block with different PR intervals, QRS durations, heart rates and the risk of heart failure: a register-based cohort study using ECG data from the primary care setting.

Aim: Left bundle branch block (LBBB) is associated with an increased risk of heart failure (HF). We assessed the impact of common ECG parameters on this association using large-scale data.

Methods And Results: Using ECGs recorded in a large primary care population from 2001 to 2011, we identified HF-naive patients with a first-time LBBB ECG.

Cardiac Rehabilitation for Patients Treated for Atrial Fibrillation With Ablation Has Long-Term Effects: 12-and 24-Month Follow-up Results From the Randomized CopenHeart Trial.

Objective: To assess outcomes at 12 and 24 months after participation in a multidisciplinary cardiac rehabilitation program plus usual care compared with usual care alone for patients treated for atrial fibrillation with catheter ablation.

Design: Long-term follow-up on the randomized CopenHeart trial.

Setting: Patients were enrolled and outcome assessed at the hospital and the intervention were carried out at the hospital or at local rehabilitation centers.

Functional phenotype variations of two novel K 7.1 mutations identified in patients with Long QT syndrome.

Background: The slow delayed rectifier potassium current I is crucial for the repolarization of the cardiac action potential. It is conducted by the voltage-gated channel K 7.1 encoded by KCNQ1, together with its β-subunit KCNE1.

Genome-wide association study identifies locus at chromosome 2q32.1 associated with syncope and collapse.

Aims: Syncope is a common condition associated with frequent hospitalization or visits to the emergency department. Family aggregation and twin studies have shown that syncope has a heritable component. We investigated whether common genetic variants predispose to syncope and collapse.

Deletion in mice of X-linked, Brugada syndrome- and atrial fibrillation-associated Kcne5 augments ventricular K currents and predisposes to ventricular arrhythmia.

KCNE5 is an X-linked gene encoding KCNE5, an ancillary subunit to voltage-gated potassium (K) channels. Human KCNE5 mutations are associated with atrial fibrillation (AF)- and Brugada syndrome (BrS)-induced cardiac arrhythmias that can arise from increased potassium current in cardiomyocytes. Seeking to establish underlying molecular mechanisms, we created and studied Kcne5 knockout ( Kcne5) mice.

Brugada Syndrome-Associated Genetic Loci Are Associated With J-Point Elevation and an Increased Risk of Cardiac Arrest.

A previous genome-wide association study found three genetic loci, rs9388451, rs10428132, and rs11708996, to increase the risk of Brugada Syndrome (BrS). Since the effect of these loci in the general population is unknown, we aimed to investigate the effect on electrocardiogram (ECG) parameters and outcomes in the general population. A cohort of 6,161 individuals (median age 45 [interquartile range (IQR) 40-50] years, 49% males), with available digital ECGs, was genotyped and subsequently followed for a median period of 13 [IQR 12.

PKD Phosphorylation as Novel Pathway of KV11.1 Regulation.

Background/aims: The voltage-gated potassium channel KV11.1 has been originally cloned from the brain and is expressed in a variety of tissues. The role of phosphorylation for channel function is a matter of debate.

Multi-ethnic genome-wide association study for atrial fibrillation.

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis.

Functional consequences of genetic variation in sodium channel modifiers in early onset lone atrial fibrillation.

Aim: We investigated the effect of variants in genes encoding sodium channel modifiers SNTA1 and GPD1L found in early onset atrial fibrillation (AF) patients.

Patients & Methods: Genetic screening in patients with early onset lone AF revealed three variants in GPD1L and SNTA1 in three AF patients. Functional analysis was performed by patch-clamp electrophysiology.

Multiple genetic variations in sodium channel subunits in a case of sudden infant death syndrome.

Background: Dysfunction of Na 1.5 encoded by SCN5A accounts for approximately half of the channelopathic SIDS cases. We investigated the functional effect of two gene variants identified in the same patient, one in SCN5A and one in SCN1Bb.

Next-generation sequencing of AV nodal reentrant tachycardia patients identifies broad spectrum of variants in ion channel genes.

Atrioventricular nodal reentry tachycardia (AVNRT) is the most common form of regular paroxysmal supraventricular tachycardia. This arrhythmia affects women twice as frequently as men, and is often diagnosed in patients <40 years of age. Familial clustering, early onset of symptoms and lack of structural anomaly indicate involvement of genetic factors in AVNRT pathophysiology.

Effect of Rehabilitation on Sleep Quality After Ablation for Atrial Fibrillation: Data From a Randomized Trial.

Background: Low sleep quality is common in patients with atrial fibrillation (AF). Positive effects of cardiac rehabilitation on patients treated for AF with ablation have been found, but whether cardiac rehabilitation affects sleep quality is unknown. The objectives of this study were to investigate (1) differences in sleep quality between cardiac rehabilitation and usual care groups and (2) whether other factors could affect sleep quality.

Analysis of 60 706 Exomes Questions the Role of De Novo Variants Previously Implicated in Cardiac Disease.

Background: De novo variants in the exome occur at a rate of 1 per individual per generation, and because of the low reproductive fitness for de novo variants causing severe disease, the likelihood of finding these as standing variations in the general population is low. Therefore, this study sought to evaluate the pathogenicity of de novo variants previously associated with cardiac disease based on a large population-representative exome database.

Methods And Results: We performed a literature search for previous publications on de novo variants associated with severe arrhythmias and structural heart diseases and investigated whether these variants were present in the Exome Aggregation Consortium (ExAC) database (n=60 706).

SUMO co-expression modifies K 11.1 channel activity.

Aim: The voltage-gated potassium channel K 11.1 is the molecular basis for the I current, which plays an important role in cardiac physiology. Its malfunction is associated with both inherited and acquired cardiac arrhythmias.

Natriuretic Propeptides as Markers of Atrial Fibrillation Burden and Recurrence (from the AMIO-CAT Trial).

Natriuretic peptides are established plasma markers of systolic heart failure, but their usefulness for the evaluation of atrial fibrillation (AF) is unknown. We examined mid-regional pro-atrial natriuretic peptide (MR-proANP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients undergoing ablation for AF. A subpopulation of 102 patients (median age 60 [52;65], 82% male) from the AMIO-CAT trial (Recurrence of arrhythmia following short-term oral AMIOdarone after CATheter ablation for atrial fibrillation: a double-blind, randomized, placebo-controlled study) undergoing ablation for paroxysmal (n = 55) or persistent (n = 47) AF was studied.

Sudden unexpected death caused by stroke: A nationwide study among children and young adults in Denmark.

Background Stroke is the fifth leading cause of death in young individuals globally. Data on the burden of sudden death by stroke are sparse in the young. Aims The aim of this study was to report mortality rates, cause of death, stroke subtype, and symptoms in children and young adults who suffered sudden death by stroke.

Sex differences in health status and rehabilitation outcomes in patients with atrial fibrillation treated with ablation: Results from the CopenHeartRFA trial.

Background: Increased physical capacity after comprehensive rehabilitation in patients with atrial fibrillation (AF) undergoing ablation has been found in the CopenHeartRFA trial. The purpose of this study was to investigate: (a) sex differences in health status, psychological distress and quality of life, (b) sex differences in rehabilitation outcomes and (c) predictors of effect of rehabilitation.

Methods: We conducted an exploratory analysis of data from the randomized CopenHeartRFA trial, where patients treated with ablation were randomized with 1:1 to comprehensive rehabilitation consisting of a physical exercise program and psycho-educational consultations versus usual care.

Deep sequencing of atrial fibrillation patients with mitral valve regurgitation shows no evidence of mosaicism but reveals novel rare germline variants.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Valvular heart disease is a strong predictor, yet the underlying molecular mechanisms are unknown.

Objective: The purpose of this study was to investigate the prevalence of somatic variants in AF candidate genes in an AF patient population undergoing surgery for mitral valve regurgitation (MVR) to determine whether these patients are genetically predisposed to AF.

Unsupervised Idealization of Ion Channel Recordings by Minimum Description Length: Application to Human PIEZO1-Channels.

Researchers can investigate the mechanistic and molecular basis of many physiological phenomena in cells by analyzing the fundamental properties of single ion channels. These analyses entail recording single channel currents and measuring current amplitudes and transition rates between conductance states. Since most electrophysiological recordings contain noise, the data analysis can proceed by idealizing the recordings to isolate the true currents from the noise.

Complications after implantation of a new-generation insertable cardiac monitor: Results from the LOOP study.

Background: Insertable cardiac monitors (ICM) are leadless devices utilized in long-term monitoring of the heart rhythm. The implantation procedure of the new-generation ICMs is minimally invasive, but little experience exists regarding complications. We thus aimed to investigate adverse events (AE) according to procedure-related characteristics after implantation of a large number of new-generation ICMs.

Electrocardiographic PR Interval Duration and Cardiovascular Risk: Results From the Copenhagen ECG Study.

Background: Because of ambiguous reports in the literature, we aimed to investigate the association between PR interval and the risk of all-cause and cardiovascular death, heart failure, and pacemaker implantation, allowing for a nonlinear relationship.

Methods: We included 293,111 individuals, corresponding to one-third of the population in the greater region of Copenhagen. These individuals had a digital electrocardiogram recorded in a general practitioner's core facility from 2001-2011.