Remote monitoring of atrial fibrillation recurrence using mHealth technology (REMOTE-AF).

Aims: This proof-of-concept study sought to evaluate changes in heart rate (HR) obtained from a consumer wearable device and compare against implantable loop recorder (ILR)-detected recurrence of atrial fibrillation (AF) and atrial tachycardia (AT) after AF ablation.

Methods And Results: REMOTE-AF (NCT05037136) was a prospectively designed sub-study of the CASA-AF randomized controlled trial (NCT04280042). Participants without a permanent pacemaker had an ILR implanted at their index ablation procedure for longstanding persistent AF.

Decrement Evoked Potential (DEEP) Mapping of the Atria: Unmasking Atrial Fibrillation Substrate.

Background: Atrial myopathy may underlie the progression of atrial fibrillation (AF) from a treatable disease to an irreversible condition with poor ablation outcomes. Electrophysiological methods to unmask areas prone to re-entry initiation could be key to defining latent atrial myopathy.

Methods: Consecutive patients referred for AF ablation were prospectively included at four institutions.

Molecular basis of ventricular arrhythmogenicity in a Pgc-1α deficient murine model.

Mitochondrial dysfunction underlying metabolic disorders such as obesity and diabetes mellitus is strongly associated with cardiac arrhythmias. Murine Pgc-1α hearts replicate disrupted mitochondrial function and model the associated pro-arrhythmic electrophysiological abnormalities. Quantitative PCR, western blotting and histological analysis were used to investigate the molecular basis of the electrophysiological changes associated with mitochondrial dysfunction.

Individualized ablation strategy to treat persistent atrial fibrillation: Core-to-boundary approach guided by charge-density mapping.

Background: Noncontact charge-density mapping allows rapid real-time global mapping of atrial fibrillation (AF), offering the opportunity for a personalized ablation strategy.

Objective: The purpose of this study was to compare the 2-year outcome of an individualized strategy consisting of pulmonary vein isolation (PVI) plus core-to-boundary ablation (targeting the conduction pattern core with an extension to the nearest nonconducting boundary) guided by charge-density mapping, with an empirical PVI plus posterior wall electrical isolation (PWI) strategy.

Methods: Forty patients (age 62 ± 12 years; 29 male) with persistent AF (10 ± 5 months) prospectively underwent charge-density mapping-guided PVI, followed by core-to-boundary stepwise ablation until termination of AF or depletion of identified cores.

Molecular basis of arrhythmic substrate in ageing murine peroxisome proliferator-activated receptor γ co-activator deficient hearts modelling mitochondrial dysfunction.

Introduction: Ageing and chronic metabolic disorders are associated with mitochondrial dysfunction and cardiac pro-arrhythmic phenotypes which were recently attributed to slowed atrial and ventricular action potential (AP) conduction in peroxisome proliferator-activated receptor γ co-activator deficient (Pgc-1β-/-) mice.

Methods: We compared expression levels of voltage-gated Na+ channel (NaV1.5) and gap junction channels, Connexins 40 and 43 (Cx40 and Cx43) in the hearts of young and old, and wild-type (WT) and Pgc-1β-/- mice.

Atrial Transcriptional Profiles of Molecular Targets Mediating Electrophysiological Function in Aging and β Deficient Murine Hearts.

Background: Deficiencies in the transcriptional co-activator, peroxisome proliferative activated receptor, gamma, coactivator-1β are implicated in deficient mitochondrial function. The latter accompanies clinical conditions including aging, physical inactivity, obesity, and diabetes. Recent electrophysiological studies reported that β mice recapitulate clinical age-dependent atrial pro-arrhythmic phenotypes.

Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse.

Mutations in the cardiac ryanodine receptor Ca release channel (RyR2) can cause deadly ventricular arrhythmias and atrial fibrillation (AF). The RyR2-P2328S mutation produces catecholaminergic polymorphic ventricular tachycardia (CPVT) and AF in hearts from homozygous RyR2 (denoted RyR2) mice. We have now examined P2328S RyR2 channels from RyR2 hearts.

Ageing in mice modelling mitochondrial dysfunction induces differential expression of a range of genes regulating ventricular electrophysiology.

Mice deficient in mitochondrial promoter peroxisome proliferator activated receptor-γ co-activator-1β ( ) is a valuable model for metabolic diseases and has been found to present with several pathologies including ventricular arrhythmia. In the present study, our aim was to shed light on the molecular mechanisms behind the observed arrhythmic substrate by studying how the expression of selected genes critical for cardiac function differs in wild-type (WT) compared with knockout mice and young compared with aged mice. We found that a clear majority of genes are down-regulated in the ventricular tissue compared with the WT.

Sodium current inhibition following stimulation of exchange protein directly activated by cyclic-3',5'-adenosine monophosphate (Epac) in murine skeletal muscle.

We investigated effects of pharmacological triggering of exchange protein directly activated by cyclic-3',5'-adenosine monophosphate (Epac) on Nav1.4 currents from intact murine (C67BL6) skeletal muscle fibres for the first time. This employed a loose patch clamp technique which examined ionic currents in response to superimposed 10-ms V steps to varying degrees of depolarisation, followed by V steps to a fixed, +100 mV depolarisation relative to resting membrane potential following 40 mV hyperpolarising prepulses of 50 ms duration.

Gene and Protein Expression Profile of Selected Molecular Targets Mediating Electrophysiological Function in Deficient Murine Atria.

Increases in the prevalence of obesity, insulin resistance, and metabolic syndrome has led to the increase of atrial fibrillation (AF) cases in the developed world. These AF risk factors are associated with mitochondrial dysfunction, previously modelled using peroxisome proliferator activated receptor-γ (PPARγ) coactivator-1 ()-deficient murine cardiac models. We explored gene and protein expression profiles of selected molecular targets related to electrophysiological function in murine atria.

Reduced cardiomyocyte Na current in the age-dependent murine Pgc-1β model of ventricular arrhythmia.

Peroxisome proliferator-activated receptor-γ coactivator-1 deficient (Pgc-1β ) murine hearts model the increased, age-dependent, ventricular arrhythmic risks attributed to clinical conditions associated with mitochondrial energetic dysfunction. These were accompanied by compromised action potential (AP) upstroke rates and impaired conduction velocities potentially producing arrhythmic substrate. We tested a hypothesis implicating compromised Na current in these electrophysiological phenotypes by applying loose patch-clamp techniques in intact young and aged, wild-type (WT) and Pgc-1β , ventricular cardiomyocyte preparations for the first time.

Arrhythmogenic mechanisms of obstructive sleep apnea in heart failure patients.

Heart failure (HF) affects 23 million people worldwide and results in 300000 annual deaths. It is associated with many comorbidities, such as obstructive sleep apnea (OSA), and risk factors for both conditions overlap. Eleven percent of HF patients have OSA and 7.

Ventricular pro-arrhythmic phenotype, arrhythmic substrate, ageing and mitochondrial dysfunction in peroxisome proliferator activated receptor-γ coactivator-1β deficient (Pgc-1β) murine hearts.

Introduction: Ageing and age-related bioenergetic conditions including obesity, diabetes mellitus and heart failure constitute clinical ventricular arrhythmic risk factors.

Materials And Methods: Pro-arrhythmic properties in electrocardiographic and intracellular recordings were compared in young and aged, peroxisome proliferator-activated receptor-γ coactivator-1β knockout (Pgc-1β) and wild type (WT), Langendorff-perfused murine hearts, during regular and programmed stimulation (PES), comparing results by two-way ANOVA.

Results And Discussion: Young and aged Pgc-1β showed higher frequencies and durations of arrhythmic episodes through wider PES coupling-interval ranges than WT.

Cardiomyocyte ionic currents in intact young and aged murine Pgc-1β atrial preparations.

Introduction: Recent studies reported that energetically deficient murine Pgc-1β hearts replicate age-dependent atrial arrhythmic phenotypes associated with their corresponding clinical conditions, implicating action potential (AP) conduction slowing consequent upon reduced AP upstroke rates.

Materials And Methods: We tested a hypothesis implicating Na current alterations as a mechanism underlying these electrophysiological phenotypes. We applied loose patch-clamp techniques to intact young and aged, WT and Pgc-1β, atrial cardiomyocyte preparations preserving their in vivo extracellular and intracellular conditions.

Epac-induced ryanodine receptor type 2 activation inhibits sodium currents in atrial and ventricular murine cardiomyocytes.

Acute RyR2 activation by exchange protein directly activated by cAMP (Epac) reversibly perturbs myocyte Ca homeostasis, slows myocardial action potential conduction, and exerts pro-arrhythmic effects. Loose patch-clamp studies, preserving in vivo extracellular and intracellular conditions, investigated Na current in intact cardiomyocytes in murine atrial and ventricular preparations following Epac activation. Depolarising steps to varying test voltages activated typical voltage-dependent Na currents.

Pro-arrhythmic atrial phenotypes in incrementally paced murine Pgc1β hearts: effects of age.

What is the central question of this study? Can we experimentally replicate atrial pro-arrhythmic phenotypes associated with important chronic clinical conditions, including physical inactivity, obesity, diabetes mellitus and metabolic syndrome, compromising mitochondrial function, and clarify their electrophysiological basis? What is the main finding and its importance? Electrocardiographic and intracellular cardiomyocyte recording at progressively incremented pacing rates demonstrated age-dependent atrial arrhythmic phenotypes in Langendorff-perfused murine Pgc1β hearts for the first time. We attributed these to compromised action potential conduction and excitation wavefronts, whilst excluding alterations in recovery properties or temporal electrophysiological instabilities, clarifying these pro-arrhythmic changes in chronic metabolic disease. Atrial arrhythmias, most commonly manifesting as atrial fibrillation, represent a major clinical problem.

Age-dependent electrocardiographic changes in Pgc-1β deficient murine hearts.

Increasing evidence implicates chronic energetic dysfunction in human cardiac arrhythmias. Mitochondrial impairment through Pgc-1β knockout is known to produce a murine arrhythmic phenotype. However, the cumulative effect of this with advancing age and its electrocardiographic basis have not been previously studied.

The effects of ageing and adrenergic challenge on electrocardiographic phenotypes in a murine model of long QT syndrome type 3.

Long QT Syndrome 3 (LQTS3) arises from gain-of-function Na1.5 mutations, prolonging action potential repolarisation and electrocardiographic (ECG) QT interval, associated with increased age-dependent risk for major arrhythmic events, and paradoxical responses to β-adrenergic agents. We investigated for independent and interacting effects of age and Scn5a+/ΔKPQ genotype in anaesthetised mice modelling LQTS3 on ECG phenotypes before and following β-agonist challenge, and upon fibrotic change.

Effects of ageing on pro-arrhythmic ventricular phenotypes in incrementally paced murine Pgc-1β hearts.

A range of chronic clinical conditions accompany cardiomyocyte energetic dysfunction and constitute independent risk factors for cardiac arrhythmia. We investigated pro-arrhythmic and arrhythmic phenotypes in energetically deficient C57BL mice with genetic ablation of the mitochondrial promoter peroxisome proliferator-activated receptor-γ coactivator-1β (Pgc-1β), a known model of ventricular arrhythmia. Pro-arrhythmic and cellular action potential (AP) characteristics were compared in intact Langendorff-perfused hearts from young (12-16 week) and aged (> 52 week), wild-type (WT) and Pgc-1β mice.

Ion channels, long QT syndrome and arrhythmogenesis in ageing.

Ageing is associated with increased prevalences of both atrial and ventricular arrhythmias, reflecting disruption of the normal sequence of ion channel activation and inactivation generating the propagated cardiac action potential. Experimental models with specific ion channel genetic modifications have helped clarify the interacting functional roles of ion channels and how their dysregulation contributes to arrhythmogenic processes at the cellular and systems level. They have also investigated interactions between these ion channel abnormalities and age-related processes in producing arrhythmic tendency.

The RyR2-P2328S mutation downregulates Nav1.5 producing arrhythmic substrate in murine ventricles.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) predisposes to ventricular arrhythmia due to altered Ca(2+) homeostasis and can arise from ryanodine receptor (RyR2) mutations including RyR2-P2328S. Previous reports established that homozygotic murine RyR2-P2328S (RyR2 (S/S)) hearts show an atrial arrhythmic phenotype associated with reduced action potential (AP) conduction velocity and sodium channel (Nav1.5) expression.

Quinine for muscle cramps.

Background: Muscle cramps can occur anywhere and for many reasons. Quinine has been used to treat cramps of all causes. However, controversy continues about its efficacy and safety.

Standalone balloon aortic valvuloplasty: indications and outcomes from the UK in the transcatheter valve era.

Objectives: We sought to characterize UK-wide balloon aortic valvuloplasty (BAV) experience in the TAVI era.

Background: BAV for acquired calcific aortic stenosis is in a phase of renaissance, largely due to the development of transcatheter aortic valve implantation (TAVI).

Methods: Data from 423 patients at 14 centers across the UK were analyzed.

Quinine for muscle cramps.

Background: Muscle cramps can occur anywhere and for many reasons. Quinine has been used to treat cramps of all causes. However, controversy continues about its efficacy and safety.