Impact of Multidirectional Pacing on Activation and Repolarization Parameters to Localize Ischemic Ventricular Tachycardia Circuits.

Background: In ventricular tachycardia (VT), optimal substrate mapping strategies identifying arrhythmogenic sites are not established.

Objectives: This study sought to evaluate multidirectional pacing on the distribution of specific conduction and repolarization metrics to localize re-entrant VT sites in a porcine infarct model.

Methods: Substrate maps were created in 13 pigs with chronic myocardial infarction using the Advisor HD Grid (Abbott) during right ventricular (RV), left ventricular, biventricular pacing (BIV), and sinus rhythm (SR).

Focal monopolar pulsed field ablation from within the great cardiac vein for idiopathic premature ventricular contractions after failed radiofrequency ablation.

Background: Idiopathic epicardial premature ventricular contractions (PVCs) originating from the left ventricular summit are difficult to eliminate.

Objective: The purpose of this study was to describe the feasibility and procedural safety of monopolar biphasic focal pulsed field ablation (F-PFA) from within the great cardiac vein (GCV) for treatment of idiopathic epicardial PVCs.

Methods: In 4 pigs, F-PFA (Centauri, CardioFocus) was applied from within the GCV followed by macroscopic gross analysis.

Glucagon-like peptide-1 increases heart rate by a direct action on the sinus node.

Aims: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used to treat type 2 diabetes and obesity. Albeit cardiovascular outcomes generally improve, treatment with GLP-1 RAs is associated with increased heart rate, the mechanism of which is unclear.

Methods And Results: We employed a large animal model, the female landrace pig, and used multiple in vivo and ex vivo approaches including pharmacological challenges, electrophysiology, and high-resolution mass spectrometry to explore how GLP-1 elicits an increase in heart rate.

Catheter-based pulmonary vein isolation fails to prevent transient atrial arrhythmogenic changes related to acute obstructive respiratory events in a porcine model.

Aims: Pulmonary vein isolation (PVI) is the corner stone of modern rhythm control strategies in patients with atrial fibrillation (AF). Sleep-disordered breathing (SDB) is prevalent in more than 50% of patients undergoing AF ablation, and studies have indicated a greater recurrence rate after PVI in patients with SDB. Herein, we study the effect of catheter-based PVI on AF in a pig model for SDB.

Inhibition of the acetylcholine-regulated potassium current prevents transient apnea-related atrial arrhythmogenic changes in a porcine model.

Background: More than 50% of patients with atrial fibrillation (AF) suffer from sleep disordered breathing (SDB). Obstructive respiratory events contribute to a transient, vagally mediated atrial arrhythmogenic substrate, which is resistant to most available antiarrhythmic drugs.

Objective: The purpose of this study was to investigate the effect of pharmacologic inhibition of the G-protein-gated acetylcholine-regulated potassium current (I) with and without acute autonomic nervous system activation by nicotine in a pig model for obstructive respiratory events.

3D-electroanatomical mapping of the left atrium and catheter-based pulmonary vein isolation in pigs: A practical guide.

Aim: To propose a standardized workflow for 3D-electroanatomical mapping guided pulmonary vein isolation in pigs.

Materials And Methods: Danish female landrace pigs were anaesthetized. Ultrasound-guided puncture of both femoral veins was performed and arterial access for blood pressure measurement established.

Pharmacological inhibition of SK-channels with AP14145 prevents atrial arrhythmogenic changes in a porcine model for obstructive respiratory events.

Background: Obstructive sleep apnea (OSA) creates a complex substrate for atrial fibrillation (AF), which is refractory to many clinically available pharmacological interventions. We investigated atrial antiarrhythmogenic properties and ventricular electrophysiological safety of small-conductance Ca -activated K (SK)-channel inhibition in a porcine model for obstructive respiratory events.

Methods: In spontaneously breathing pigs, obstructive respiratory events were simulated by intermittent negative upper airway pressure (INAP) applied via a pressure device connected to the intubation tube.

Mechanisms and Therapeutic Opportunities in Atrial Fibrillation in Relationship to Alcohol Use and Abuse.

Excessive drinking has detrimental effects on the cardiovascular system. Atrial fibrillation (AF) after alcohol binge drinking, also named "holiday heart syndrome," is well established. However, chronic lower levels of alcohol intake also may increase AF risk.

Pharmacological inhibition of acetylcholine-regulated potassium current ( ) prevents atrial arrhythmogenic changes in a rat model of repetitive obstructive respiratory events.

Background: In obstructive sleep apnea (OSA), intermittent hypoxemia and intrathoracic pressure fluctuations may increase atrial fibrillation (AF) susceptibility by cholinergic activation.

Objective: To investigate short-term atrial electrophysiological consequences of obstructive respiratory events, simulated by intermittent negative upper airway pressure (INAP), and the role of atrial acetylcholine-regulated potassium current ( ) activated by the M receptor.

Methods: In sedated (2% isoflurane), spontaneously breathing rats, INAP was applied noninvasively by a negative pressure device for 1 minute, followed by a resting period of 4 minutes.

Renal Denervation Prevents Atrial Arrhythmogenic Substrate Development in CKD.

Background: In patients with chronic kidney disease (CKD), atrial fibrillation (AF) is highly prevalent and represents a major risk factor for stroke and death. CKD is associated with atrial proarrhythmic remodeling and activation of the sympathetic nervous system. Whether reduction of the sympathetic nerve activity by renal denervation (RDN) inhibits AF vulnerability in CKD is unknown.

Sleep apnea and atrial fibrillation: challenges in clinical and translational research.

Introduction: Sleep-disordered breathing (SDB) is present in 21-74% of all patients with atrial fibrillation (AF). Treatment of SDB by positive airway pressure may help to prevent recurrence of AF after electrical cardioversion and help to improve AF ablation success rates in non-randomized studies.

Areas Covered: In this review, the current understanding of the atrial arrhythmogenic pathophysiology of SDB is summarized, and diagnostic and therapeutic challenges in AF patients are discussed.

Arrhythmogenic mechanisms of acute obstructive respiratory events in a porcine model of drug-induced long QT.

Background: Obstructive sleep apnea is associated with increased risk of sudden cardiac death.

Objective: The purpose of this study was to elucidate changes in ventricular repolarization and electromechanical interaction during obstructive respiratory events simulated by intermittent negative upper airway pressure (INAP) in pigs. We also investigated the effect of a reduced repolarization reserve in drug-induced long QT (LQT) following INAP-induced changes in ventricular repolarization.

Nocturnal hypoxemic burden during positive airway pressure treatment across different central sleep apnea etiologies.

Introduction: Nocturnal hypoxemia is associated with increased cardiovascular mortality. Here, we assess whether positive airway pressure by adaptive servo-ventilation (ASV) reduces nocturnal hypoxemic burden in patients with primary central sleep apnea (primary CSA), or heart failure related central sleep apnea (CSA-HF) and treatment emergent central sleep apnea (TECSA).

Methods: Overnight oximetry data from 328 consecutive patients who underwent ASV initiation between March 2010 and May 2018 were retrospectively analyzed.

Repeated exposure to transient obstructive sleep apnea-related conditions causes an atrial fibrillation substrate in a chronic rat model.

Background: High night-to-night variability in obstructive sleep apnea (OSA) is associated with atrial fibrillation (AF). Obstructive apneas are characterized by intermittent deoxygenation-reoxygenation and intrathoracic pressure swings during ineffective inspiration against occluded upper airways.

Objective: We elucidated the effect of repeated exposure to transient OSA conditions simulated by intermittent negative upper airway pressure (INAP) on the development of an AF substrate.

Inhibition of sodium-proton-exchanger subtype 3-mediated sodium absorption in the gut: A new antihypertensive concept.

Arterial hypertension is one of the main contributors to cardiovascular diseases, including stroke, heart failure, and coronary heart disease. Salt plays a major role in the regulation of blood pressure and is one of the most critical factors for hypertension and stroke. At the individual level, effective salt reduction is difficult to achieve and available methods for managing sodium balance are lacking for many patients.

Cathepsin A contributes to left ventricular remodeling by degrading extracellular superoxide dismutase in mice.

In the heart, the serine carboxypeptidase cathepsin A (CatA) is distributed between lysosomes and the extracellular matrix (ECM). CatA-mediated degradation of extracellular peptides may contribute to ECM remodeling and left ventricular (LV) dysfunction. Here, we aimed to evaluate the effects of CatA overexpression on LV remodeling.

Pharmacological inhibition of sodium-proton-exchanger subtype 3-mediated sodium absorption in the gut reduces atrial fibrillation susceptibility in obese spontaneously hypertensive rats.

Background: Increased sodium uptake has been shown to contribute to hypertension and cardiac end-organ damage. The sodium-proton-exchanger subtype 3 (NHE3) is an important mediator of intestinal sodium absorption. Whether a reduction in intestinal sodium absorption can prevent the development of an atrial arrhythmogenic substrate in hypertension is unknown.

The association between different features of sleep-disordered breathing and blood pressure: A cross-sectional study.

Sleep disordered breathing (SDB) is highly prevalent in patients with high blood pressure (BP). Severity of SDB can be evaluated by the number of apneas and hypopneas per hour (AHI) or by measures of hypoxia. The objective of this study was to assess the association between different measures of SDB and BP.

Concomitant Obesity and Metabolic Syndrome Add to the Atrial Arrhythmogenic Phenotype in Male Hypertensive Rats.

Background: Besides hypertension, obesity and the metabolic syndrome have recently emerged as risk factors for atrial fibrillation. This study sought to delineate the development of an arrhythmogenic substrate for atrial fibrillation in hypertension with and without concomitant obesity and metabolic syndrome.

Methods And Results: We compared obese spontaneously hypertensive rats (SHR-obese, n=7-10) with lean hypertensive controls (SHR-lean, n=7-10) and normotensive rats (n=7-10).

[Update: Cardiovascular Sleep Medicine].

The prevalence of sleep-disordered breathing (SDB) is high in patients with cardiovascular diseases. Typical symptoms like daytime sleepiness can be absent and those patients may report unspecific, therapy-resistant symptoms related to their underlying disease. Particularly sleep-related symptoms like nocturia, nocturnal dyspnea and pectangina can be present.