Pseudo repetitive non-reentrant ventriculoatrial synchrony: Current challenges.

BACKGROUND: We recently described a novel pacemaker-mediated arrhythmia in Abbott cardiac implantable electronic devices (CIED), called pseudo-RNRVAS, that mimics repetitive non-reentrant ventriculoatrial synchrony (RNRVAS), but can appear in patients with ventriculoatrial (VA) block. It is caused by sinus-p-waves, trapped in the post-ventricular atrial refractory period (PVARP), which mimic VA conduction. The p-waves are followed by atrial pacing during the myocardial refractory time, which can trigger atrial fibrillation (AF). Pseudo-RNRVAS and RNRVAS are probably more common than appreciated, but the recognition and differentiation of the two can be challenging because most CIEDs do not recognize and store them. OBJECTIVE: We illustrate practical challenges in the assessment of Pseudo-RNRVAS and provide programming options that proved safe and effective for preventing Pseudo-RNRVAS and reducing the risk for typical RNRVAS. METHODS AND RESULTS: We illustrate in 10 patients the characteristics of Pseudo-RNRVAS and their treatment. The outcome regarding the recurrence of pseudo-RNRVAS after 6 months of follow-up was collected. Inappropriate atrial pacing during pseudo-RNRVAS resulted in AF in six patients. After shortening the PVARP in nine, inactivation/reduction of rate response in four, and reduction of the basic pacing rate in one patient, pseudo-RNRVAS was avoided in eight patients and reduced in one. In one patient AF became permanent. CONCLUSIONS: Pseudo-RNRVAS is a pacemaker-mediated arrhythmia that can appear in patients without VA conduction and may lead to AF. The suggested adjustments of pacing parameters were safe and effective in preventing the arrhythmia.

Phenotype-tissue expression and exploration (PTEE) resource facilitates the choice of tissue for RNA-seq-based clinical genetics studies.

BACKGROUND: RNA-seq emerges as a valuable method for clinical genetics. The transcriptome is "dynamic" and tissue-specific, but typically the probed tissues to analyze (TA) are different from the tissue of interest (TI) based on pathophysiology. RESULTS: We developed Phenotype-Tissue Expression and Exploration (PTEE), a tool to facilitate the decision about the most suitable TA for RNA-seq. We integrated phenotype-annotated genes, used 54 tissues from GTEx to perform correlation analyses and identify expressed genes and transcripts between TAs and TIs. We identified skeletal muscle as the most appropriate TA to inquire for cardiac arrhythmia genes and skin as a good proxy to study neurodevelopmental disorders. We also explored RNA-seq limitations and show that on-off switching of gene expression during ontogenesis or circadian rhythm can cause blind spots for RNA-seq-based analyses. CONCLUSIONS: PTEE aids the identification of tissues suitable for RNA-seq for a given pathology to increase the success rate of diagnosis and gene discovery. PTEE is freely available at https://bioinf.eva.mpg.de/PTEE/.

Novel Pacemaker-Mediated Arrhythmia Without Ventriculoatrial Conduction Can Induce Atrial Fibrillation.

Cardiovascular implantable electronic devices can initiate and sustain pacemaker-mediated arrhythmias. Endless loop tachycardia and repetitive non-re-entrant ventriculoatrial synchrony (RNRVAS) are well-described examples of pacemaker-mediated arrhythmias. However, such arrhythmias only occur in the presence of ventriculoatrial conduction. We identified a novel pacemaker-mediated arrhythmia that closely mimics RNRVAS but in the absence of ventriculoatrial conduction. We identified these arrhythmias in 9 patients, all with a St. Jude Medical/Abbott device, recorded as inappropriate mode-switch episodes by a device algorithm that includes paced events in the atrial counter. This report describes the mechanism, discusses clinical implications, and outlines programming options to eliminate this pseudo-RNRVAS.

Obesity-An Update on the Basic Pathophysiology and Review of Recent Therapeutic Advances.

Obesity represents a major public health problem with a prevalence increasing at an alarming rate worldwide. Continuous intensive efforts to elucidate the complex pathophysiology and improve clinical management have led to a better understanding of biomolecules like gut hormones, antagonists of orexigenic signals, stimulants of fat utilization, and/or inhibitors of fat absorption. In this article, we will review the pathophysiology and pharmacotherapy of obesity including intersection points to the new generation of antidiabetic drugs. We provide insight into the effectiveness of currently approved anti-obesity drugs and other therapeutic avenues that can be explored.

Flecainide-Associated Cardiogenic Shock in a Patient with Atrial Fibrillation.

Flecainide is a frequently used antiarrhythmic drug, recommended by current guidelines as a first-line treatment option for restoring and maintaining sinus rhythm in patients with atrial fibrillation and no significant structural heart disease. In overdose, it can induce severe cardiogenic shock. Cardiogenic shock after a therapeutic dose of flecainide in patients without contraindication has not yet been reported in literature. Case Summary. We report a case of flecainide-associated cardiogenic shock in a 52-year-old woman with paroxysmal atrial fibrillation after a therapeutic dose of flecainide. Pharmacological cardioversion of symptomatic tachyarrhythmic atrial fibrillation with flecainide was unsuccessful and shortly after, she developed cardiogenic shock with severely reduced LVEF. Electrical cardioversion was also unsuccessful. Coronarography was unremarkable, and the cardiac MRI showed no signs of inflammation or fibrosis. After amiodarone loading, she converted to SR. This rare but severe complication despite adequate treatment could be explained by increased susceptibility to negative inotropic effect of flecainide as a consequence of marked tachycardia. Therefore, cautious monitoring after new administration of flecainide or the administration of a higher dose is advisable.