A governing equation for rotor and wavelet number in human clinical ventricular fibrillation: Implications for sudden cardiac death.

Background: Ventricular fibrillation (VF) is characterized by multiple wavelets and rotors. No equation to predict the number of rotors and wavelets observed during fibrillation has been validated in human VF.

Objective: The purpose of this study was to test the hypothesis that a single equation derived from a Markov M/M/∞ birth-death process could predict the number of rotors and wavelets occurring in human clinical VF.

Time-Averaged Wavefront Analysis Demonstrates Preferential Pathways of Atrial Fibrillation, Predicting Pulmonary Vein Isolation Acute Response.

Electrical activation during atrial fibrillation (AF) appears chaotic and disorganised, which impedes characterisation of the underlying substrate and treatment planning. While globally chaotic, there may be local preferential activation pathways that represent potential ablation targets. This study aimed to identify preferential activation pathways during AF and predict the acute ablation response when these are targeted by pulmonary vein isolation (PVI).

Direct in vivo assessment of global and regional mechanoelectric feedback in the intact human heart.

Background: Inhomogeneity of ventricular contraction is associated with sudden cardiac death, but the underlying mechanisms are unclear. Alterations in cardiac contraction impact electrophysiological parameters through mechanoelectric feedback. This has been shown to promote arrhythmias in experimental studies, but its effect in the in vivo human heart is unclear.

Emerging evidence for a mechanistic link between low-frequency oscillation of ventricular repolarization measured from the electrocardiogram T-wave vector and arrhythmia.

Strong recent clinical evidence links the presence of prominent oscillations of ventricular repolarization in the low-frequency range (0.04-0.15 Hz) to the incidence of ventricular arrhythmia and sudden death in post-MI patients and patients with ischaemic and non-ischaemic cardiomyopathy.

Assessing the ability of substrate mapping techniques to guide ventricular tachycardia ablation using computational modelling.

Background: Identification of targets for ablation of post-infarction ventricular tachycardias (VTs) remains challenging, often requiring arrhythmia induction to delineate the reentrant circuit. This carries a risk for the patient and may not be feasible. Substrate mapping has emerged as a safer strategy to uncover arrhythmogenic regions.

Complex Interaction Between Low-Frequency APD Oscillations and Beat-to-Beat APD Variability in Humans Is Governed by the Sympathetic Nervous System.

Background: Recent clinical, experimental and modeling studies link oscillations of ventricular repolarization in the low frequency (LF) (approx. 0.1 Hz) to arrhythmogenesis.

Time Course of Low-Frequency Oscillatory Behavior in Human Ventricular Repolarization Following Enhanced Sympathetic Activity and Relation to Arrhythmogenesis.

Recent studies in humans and dogs have shown that ventricular repolarization exhibits a low-frequency (LF) oscillatory pattern following enhanced sympathetic activity, which has been related to arrhythmic risk. The appearance of LF oscillations in ventricular repolarization is, however, not immediate, but it may take up to some minutes. This study seeks to characterize the time course of the action potential (AP) duration (APD) oscillatory behavior in response to sympathetic provocations, unveil its underlying mechanisms and establish a potential link to arrhythmogenesis under disease conditions.

Evaluation of the reentry vulnerability index to predict ventricular tachycardia circuits using high-density contact mapping.

Background: Identifying arrhythmogenic sites to improve ventricular tachycardia (VT) ablation outcomes remains unresolved. The reentry vulnerability index (RVI) combines activation and repolarization timings to identify sites critical for reentrant arrhythmia initiation without inducing VT.

Objective: The purpose of this study was to provide the first assessment of RVI's capability to identify VT sites of origin using high-density contact mapping and comparison with other activation-repolarization markers of functional substrate.

Mechanisms Underlying Interactions Between Low-Frequency Oscillations and Beat-to-Beat Variability of Celullar Ventricular Repolarization in Response to Sympathetic Stimulation: Implications for Arrhythmogenesis.

Enhanced beat-to-beat variability of ventricular repolarization (BVR) has been linked to arrhythmias and sudden cardiac death. Recent experimental studies on human left ventricular epicardial electrograms have shown that BVR closely interacts with low-frequency (LF) oscillations of activation recovery interval during sympathetic provocation. In this work human ventricular computational cell models are developed to reproduce the experimentally observed interactions between BVR and its LF oscillations, to assess underlying mechanisms and to establish a relationship with arrhythmic risk.

Autonomic modulation of the electrical substrate in mice haploinsufficient for cardiac sodium channels: a model of the Brugada syndrome.

A murine line haploinsufficient in the cardiac sodium channel has been used to model human Brugada syndrome: a disease causing sudden cardiac death due to lethal ventricular arrhythmias. We explored the effects of cholinergic tone on electrophysiological parameters in wild-type and genetically modified, heterozygous, knockout mice. ventricular slices showed longer refractory periods than wild-type both at baseline and during isoprenaline challenge.

Characterizing the clinical implementation of a novel activation-repolarization metric to identify targets for catheter ablation of ventricular tachycardias using computational models.

Identification of targets for catheter ablation of ventricular tachycardias (VTs) remains a significant challenge. VTs are often driven by re-entrant circuits resulting from a complex interaction between the front (activation) and tail (repolarization) of the electrical wavefront. Most mapping techniques do not take into account the tissue repolarization which may hinder the detection of ablation targets.

Simultaneous Comparison of Electrocardiographic Imaging and Epicardial Contact Mapping in Structural Heart Disease.

Background: The accuracy of ECG imaging (ECGI) in structural heart disease remains uncertain. This study aimed to provide a detailed comparison of ECGI and contact-mapping system (CARTO) electrograms.

Methods: Simultaneous epicardial mapping using CARTO (Biosense-Webster, CA) and ECGI (CardioInsight) in 8 patients was performed to compare electrogram morphology, activation time (AT), and repolarization time (RT).

Pulse Arrival Time and Pulse Interval as Accurate Markers to Detect Mechanical Alternans.

Mechanical alternans (MA) is a powerful predictor of adverse prognosis in patients with heart failure and cardiomyopathy, but its use remains limited due to the need of invasive continuous arterial pressure recordings. This study aims to assess novel cardiovascular correlates of MA in the intact human heart to facilitate affordable and non-invasive detection of MA and advance our understanding of the underlying pathophysiology. Arterial pressure, respiration, and ECG were recorded in 12 subjects with healthy ventricles during voluntarily controlled breathing at different respiratory rate, before and after administration of beta-blockers.

Mechanistic insights from targeted molecular profiling of repolarization alternans in the intact human heart.

Aims: Action potential duration (APD) alternans is an established precursor or arrhythmia and sudden cardiac death. Important differences in fundamental electrophysiological properties relevant to arrhythmia exist between experimental models and the diseased in vivo human heart. To investigate mechanisms of APD alternans using a novel approach combining intact heart and cellular cardiac electrophysiology in human in vivo.

Differences in the upslope of the precordial body surface ECG T wave reflect right to left dispersion of repolarization in the intact human heart.

Background: The relationship between the surface electrocardiogram (ECG) T wave to intracardiac repolarization is poorly understood.

Objective: The purpose of this study was to examine the association between intracardiac ventricular repolarization and the T wave on the body surface ECG (SECG).

Methods: Ten patients with a normal heart (age 35 ± 15 years; 6 men) were studied.

Left ventricular activation-recovery interval variability predicts spontaneous ventricular tachyarrhythmia in patients with heart failure.

Background: Enhanced beat-to-beat variability of repolarization is strongly linked to arrhythmogenesis and is largely due to variation in ventricular action potential duration (APD). Previous studies in humans have relied on QT interval measurements; however, a direct relationship between beat-to-beat variability of APD and arrhythmogenesis in humans has yet to be demonstrated.

Objective: This study aimed to explore the beat-to-beat repolarization dynamics in patients with heart failure at the level of ventricular APD.

Prolonged action potential duration and dynamic transmural action potential duration heterogeneity underlie vulnerability to ventricular tachycardia in patients undergoing ventricular tachycardia ablation.

Aims: Differences of action potential duration (APD) in regions of myocardial scar and their borderzones are poorly defined in the intact human heart. Heterogeneities in APD may play an important role in the generation of ventricular tachycardia (VT) by creating regions of functional block. We aimed to investigate the transmural and planar differences of APD in patients admitted for VT ablation.

Modulation of Cardiac Ventricular Excitability by GLP-1 (Glucagon-Like Peptide-1).

Background: Glucagon-like peptide-1 receptor (GLP-1R) agonists improve cardiovascular outcomes in patients with type 2 diabetes mellitus. However, systemic actions of these agents cause sympathetic activation, which is generally considered to be detrimental in cardiovascular disease. Despite significant research interest in cardiovascular biology of GLP-1, the presence of GLP-1R in ventricular cardiomyocytes remains a controversial issue, and the effects of this peptide on the electrical properties of intact ventricular myocardium are unknown.

Pharmacological Modulation of Right Ventricular Endocardial-Epicardial Gradients in Brugada Syndrome.

Background We explored the hypothesis that increased cholinergic tone exerts its proarrhythmic effects in Brugada syndrome (BrS) through increasing dispersion of transmural repolarization in patients with spontaneous and drug-induced BrS. Methods BrS and supraventricular tachycardia patients were studied after deploying an Ensite Array in the right ventricular outflow tract and a Cardima catheter in the great cardiac vein to record endo and epicardial signals, respectively. S-S restitution curves from the right ventricular apex were conducted at baseline and after edrophonium challenge to promote increased cholinergic tone.

Unraveling the Underlying Arrhythmia Mechanism in Persistent Atrial Fibrillation: Results From the STARLIGHT Study.

Background: The mechanisms that initiate and sustain persistent atrial fibrillation are not well characterized. Ablation results remain significantly worse than in paroxysmal atrial fibrillation in which the mechanism is better understood and subsequent targeted therapy has been developed. The aim of this study was to characterize and quantify patterns of activation during atrial fibrillation using contact mapping.

Beat-to-Beat Variability of Ventricular Action Potential Duration Oscillates at Low Frequency During Sympathetic Provocation in Humans.

The temporal pattern of ventricular repolarization is of critical importance in arrhythmogenesis. Enhanced beat-to-beat variability (BBV) of ventricular action potential duration (APD) is pro-arrhythmic and is increased during sympathetic provocation. Since sympathetic nerve activity characteristically exhibits burst patterning in the low frequency range, we hypothesized that physiologically enhanced sympathetic activity may not only increase BBV of left ventricular APD but also impose a low frequency oscillation which further increases repolarization instability in humans.