A Primer on the Evolving Subspecialty of Onco-Electrophysiology.

Cardio-oncology has become a well-established subspecialty because of the growing burden of cardiovascular diseases in oncology patients, resulting from the cardiac toxicities of cancer therapies and the coexistence of both conditions in the same population. As with other cardiovascular conditions, cardiac arrhythmias have emerged as an important concern in patients with cancer. However, the management of arrhythmias is more complicated in these patients because of complex interactions between oncotherapeutics and arrhythmia-treatment strategies.

Machine Learning Identifies Arrhythmogenic Features of QRS Fragmentation in Human Cardiomyopathy: Implications for Improving Risk Stratification.

Background: Heterogeneous ventricular activation can provide the substrate for ventricular arrhythmias (VA), but its manifestation on the electrocardiogram (ECG) as a risk stratifier is not well-defined.

Objective: To characterize the spatiotemporal features of QRS peaks that best predict VA in patients with cardiomyopathy (CM) using machine learning (ML).

Methods: Prospectively enrolled CM patients with prophylactic defibrillators (n=95) underwent digital, high-resolution ECG recordings during intrinsic rhythm and ventricular pacing at 100 to 120 beats/min.

Heart rate variability metrics and myocardial recovery in heart failure with reduced ejection fraction.

Purpose: Autonomic dysregulation is observed in heart failure (HF) with reduced ejection fraction (HFrEF). Abnormal heart rate variability (HRV), a measure of such dysregulation, is associated with poor prognosis in HFrEF. It is unknown if novel HRV metrics normalize in the patients with recovered ejection fraction (HFrecEF) compared to persistent HFrEF.

Role of subpulmonary right ventricle in sudden cardiac death in adults with congenital heart disease.

Despite improved childhood survival of congenital heart disease (CHD) as a result of advances in management, late-onset sudden cardiac death (SCD) from malignant ventricular arrhythmias remains a leading cause of mortality in adults with CHD. Preventing SCD in these patients requires an understanding of the underlying pathophysiological mechanisms. Many CHD patients experience significant hemodynamic stress on the subpulmonary right ventricle (RV), leading to pathologic remodeling.

Arrhythmogenic Ventricular Remodeling by Next-Generation Bruton's Tyrosine Kinase Inhibitor Acalabrutinib.

Cardiac arrhythmias remain a significant concern with Ibrutinib (IBR), a first-generation Bruton's tyrosine kinase inhibitor (BTKi). Acalabrutinib (ABR), a next-generation BTKi, is associated with reduced atrial arrhythmia events. However, the role of ABR in ventricular arrhythmia (VA) has not been adequately evaluated.

Sudden cardiac death due to ventricular arrhythmia in diabetes mellitus: A bench to bedside review.

Diabetes mellitus (DM) confers an increased risk of sudden cardiac death (SCD) independent of its associated cardiovascular comorbidities. DM induces adverse structural, electrophysiologic, and autonomic cardiac remodeling that can increase one's risk of ventricular arrhythmias and SCD. Although glycemic control and prevention of microvascular and macrovascular complications are cornerstones in the management of DM, they are not adequate for the prevention of SCD.

Impaired Cardiac AMPK (5'-Adenosine Monophosphate-Activated Protein Kinase) and Ca-Handling, and Action Potential Duration Heterogeneity in Ibrutinib-Induced Ventricular Arrhythmia Vulnerability.

Background: We recently demonstrated that acute administration of ibrutinib, a Bruton's tyrosine kinase inhibitor used in chemotherapy for blood malignancies, increases ventricular arrhythmia (VA) vulnerability. A pathway of ibrutinib-induced vulnerability to VA that can be modulated for cardioprotection remains unclear.

Methods And Results: The effects of ibrutinib on cardiac electrical activity and Ca dynamics were investigated in Langendorff-perfused hearts using optical mapping.

Knockdown of SCN5A alters metabolic-associated genes and aggravates hypertrophy in the cardiomyoblast.

SCN5A mutations have been reported to cause various cardiomyopathies in humans. Most of the SCN5A mutations causes loss of function and thereby, alters the overall cellular function. Therefore, to understand the loss of SCN5A function in cardiomyocytes, we have knocked down the SCN5A gene (SCN5A-KD) in H9c2 cells and explored the cell phenotype and molecular behaviors in the presence and absence of isoproterenol (ISO), an adrenergic receptor agonist that induces cardiac hypertrophy.

Effect of Low-Level Tragus Stimulation on Cardiac Metabolism in Heart Failure with Preserved Ejection Fraction: A Transcriptomics-Based Analysis.

Abnormal cardiac metabolism precedes and contributes to structural changes in heart failure. Low-level tragus stimulation (LLTS) can attenuate structural remodeling in heart failure with preserved ejection fraction (HFpEF). The role of LLTS on cardiac metabolism is not known.

Uncoupling cytosolic calcium from membrane voltage by transient receptor potential melastatin 4 channel (TRPM4) modulation: A novel strategy to treat ventricular arrhythmias.

The current antiarrhythmic paradigm is mainly centered around modulating membrane voltage. However, abnormal cytosolic calcium (Ca) signaling, which plays an important role in driving membrane voltage, has not been targeted for therapeutic purposes in arrhythmogenesis. There is clear evidence for bidirectional coupling between membrane voltage and intracellular Ca.

Noninvasive Vagus Nerve Stimulation in Postural Tachycardia Syndrome: A Randomized Clinical Trial.

Background: Low-level transcutaneous stimulation of the auricular branch of the vagus nerve at the tragus is antiarrhythmic and anti-inflammatory in animals and humans. Preliminary studies show that transcutaneous vagus nerve stimulation (tVNS) is beneficial in animal models of postural tachycardia syndrome (POTS).

Objectives: In this study the authors conducted a sham-controlled, double-blind, randomized clinical trial to examine the effect of tVNS on POTS over a 2-month period relative to sham stimulation.

Noninvasive low-level tragus stimulation attenuates inflammation and oxidative stress in acute heart failure.

Purpose: Acute decompensated heart failure (ADHF) is associated with inflammation, oxidative stress, and excess sympathetic drive. It is unknown whether neuromodulation would improve inflammation and oxidative stress in acute heart failure. We, therefore, performed this proof-of-concept study to evaluate the effects of neuromodulation using noninvasive low-level tragus stimulation on inflammation and oxidative stress in ADHF.

Noninvasive low-level tragus stimulation attenuates inflammation and oxidative stress in acute heart failure.

Purpose: Acute decompensated heart failure is associated with inflammation, oxidative stress, and excess sympathetic drive. It is unknown if neuromodulation would improve inflammation and oxidative stress in acute heart failure. We, therefore, performed this proof-of-concept study to evaluate the effects of neuromodulation using noninvasive low-level Tragus stimulation on inflammation and oxidative stress in ADHF.

The neurometabolic axis: A novel therapeutic target in heart failure.

Abnormal cardiac metabolism or cardiac metabolic remodeling is reported before the onset of heart failure with reduced ejection fraction (HFrEF) and is known to trigger and maintain the mechanical dysfunction and electrical, and structural abnormalities of the ventricle. A dysregulated cardiac autonomic tone characterized by sympathetic overdrive with blunted parasympathetic activation is another pathophysiological hallmark of HF. Emerging evidence suggests a link between autonomic nervous system activity and cardiac metabolism.

Restoration of calcium release synchrony: A novel target for heart failure and ventricular arrhythmia.

Myocardial calcium (Ca) signaling plays a crucial role in contractile function and membrane electrophysiology. An abnormal myocardial Ca transient is linked to heart failure and ventricular arrhythmias. At the subcellular level, the synchronous release of Ca sparks from sarcoplasmic Ca release units determines the configuration and amplitude of the global Ca transient.

Protein kinase A: A potential marker of sympathovagal imbalance in heart failure.

Mitigation of cardiac autonomic dysregulation by neuromodulation technologies is emerging as a new therapeutic modality of heart failure (HF). This recent progress has necessitated the identification of a biomarker for the quantification of sympathovagal balance, the potential target of 'neuromodulation' strategies. The currently available autonomic nervous system assessment parameters do not truly reflect the sympathovagal balance of the ventricle.