Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights from this month's issue.

                                                In our first article, Daniel Alyesh, Konstantinos Siontis and associates described myocardial calcifications in patients with ischemic cardiomyopathy undergoing ventricular tachycardia ablation in comparison to a control group of patients without ventricular tachycardia. They found that in 56 consecutive post-infarction patients, myocardial calcifications were identified in 39 or 70% of post-infarction ventricular tachycardia patients compared to 6 or 11% of patients without ventricular tachycardia. A calcification volume of 0.538 centimeters cube distinguished patients with calcification-associated ventricular tachycardia from patients without calcification-associated ventricular tachycardias; area under the curve, 0.87; sensitivity, 0.87; specificity, 0.88. A non-confluent calcification pattern was associated with ventricular tachycardia target sites independent of calcification volume, P equals 0.01. Myocardial calcifications corresponding to areas of electrical non-excitability forming a border for re-entry were found in 33% of all ventricular tachycardias for which target sites were identified, and in 62% of patients with myocardial calcifications.

                                                In our next paper, Mia Fangel and associates examined whether glycemic status evaluated by hemoglobin A1c has an effect on the risk of thromboembolism among patients with atrial fibrillation and Type 2 diabetes. They used a cohort study from 5,386 patients with incident non-valvular atrial fibrillation and Type 2 diabetes in Danish registries. Compared with patients with hemoglobin A1c of less than or equal to 48 millimole per mole, they observed a higher risk of thromboembolism among patients with hemoglobin A1c 49 to 58 millimoles per mole with a hazard ratio of 1.49 and a hemoglobin A1c greater than 58 millimole per mole with a hazard ratio of 1.59 after adjusting for confounding factors. Surprisingly, in patients with diabetes duration of 10 years or more, higher hemoglobin A1c levels were not associated with a higher risk of thromboembolism.

                                                In our next paper, Niek Beurskens and associates compared tricuspid valve dysfunction in leadless pacemaker therapy to dual chamber transvenous pacing systems. They studied 53 patients receiving a leadless pacemaker, including 28 with a Nanostim and 25 with a Micra device. Of these 53 patients, 23 or 43% had tricuspid regurgitation that was graded as being more severe at 12 months. Compared with an apical position, a right ventricular septal position of the leadless pacemaker was associated with increased tricuspid valve incompetence, odds ratio, 5.20; P equals 0.03. An increase in mitral valve regurgitation was observed in 38% of patients. Leadless pacemaker implantation resulted in a reduction of right ventricular function. Leadless pacemaker implantation was further associated with a reduction in left ventricular ejection fraction and elevated LV TI index. The changes in tricuspid regurgitation in leadless pacing group was similar to the changes in dual-chamber transvenous pacemaker group, 43% versus 38% respectively; P equals 0.39.

                                                In our next paper, Jurgen Duchenne and associates examined whether regional left ventricular glucose metabolism correlates with regional work in an animal model with reversible dyssynchrony due to pacing. In 12 sheep, after 8 weeks of right atrial and right ventricular free wall pacing, there is evidence of left ventricular dilatation and thinning of the septum and thickening of the lateral wall. The authors employed motion compensation and anatomical correction in order to provide reliable regional estimates of myocardial glucose metabolism. They found that in homogenous regional distribution of myocardial workload due to left bundle branch block triggers adaptive remodeling of the left ventricle, leading to a more homogenous load distribution per volume unit myocardium. In reverse, cardiac resynchronization therapy leads acutely to an inhomogeneous distribution of workload, which homogenizes over time due to reverse remodeling. The authors concluded that redistribution of regional loading appears as a mode of action of cardiac resynchronization therapy so that myocardial mechanics should be the main treatment target of cardiac resynchronization therapy.

                                                In our next paper, Jihye Jang and associates examined the association between local conduction velocity and late gadolinium enhancement and myocardial thickness in a swine model of healed left ventricular infarction. They studied six swine with healed myocardial infarction and two controls. The authors found a significantly slower conduction was found in late gadolinium enhancement regions, 0.33 versus 0.54 meters per second, P less than 0.001, and regions of wall thinning, 0.38 versus 0.55 meters per second, P also less than 0.001; areas with greater late gadolinium enhancement heterogeneity and wall thickness gradient exhibited slower conduction velocity.

                                                In our next paper, Xi Zhang and Xiaohui Kuang and associates studied whether restricting contact force to less than 20 grams reduces the risk of esophageal injury in patients with atrial fibrillation undergoing circumferential pulmonary vein isolation. In a prospective, single-center, randomized study, 89 consecutive patients, mean age 57.2 years, 57% men, with atrial fibrillation, 68.5% paroxysmal and 31.5% persistent were randomized to restrictive contact force group or non-contact force group. The primary end point was a rate of esophageal injury post ablation. The same power setting, similar ablation time, and average measured catheter tip temperature during posterior wall ablation just opposite to the esophagus were present in both groups, there were no cases of esophageal injury in the restricted contact force group versus 9 or 20% of cases of esophageal injury post ablation in the non-contact force group. There are similar rates of freedom from atrial tachyarrhythmias at a mean of 31.3 months follow-up, 68.2% versus 64.4%.

                                                In our next paper, J. Martijn Bos and associates examined whether sodium channel blockers like mexiletine may have a potential role in LQT1 and LQT2, two forms of potassium channel mediated long QT syndrome. They retrospectively studied 12 patients, 5 females, median age at diagnosis 14.1 years with genetically established long QT2 in 10 or a combination of LQT1/LQT2 in 1 or LQT2/LQT3 in 1, who all received mexiletine. Prior to diagnosis, six patients were symptomatic and prior to initiation of mexiletine, four patients experienced one breakthrough cardiac event on beta blocker therapy. Median age at first mexiletine dose was 24.3 years. After mexiletine, the median QTc decreased by 65 milliseconds from 547 milliseconds pre-mexiletine to 470 milliseconds post-mexiletine, P equals 0.0005 for all patients. In eight patients or 67%, the QTc decreased by 40 milliseconds with a mean decrease in QTc of 91 milliseconds, P less than 0.008. For the 11 patients maintained on mexiletine therapy, there have been no breakthrough cardiac events during follow-up.

                                                In our final paper, Andrea Mazzanti and associates assessed whether low dose quinidine in Brugada Syndrome patients reduces the occurrence of life-threatening arrhythmic events in this population. They compared the clinical course of 53 Brugada Syndrome patients treated with quinidine to that of 441 untreated controls, matched by sex, age, symptoms, and duration of observation. The 53 Brugada Syndrome patients, 89% males, median age 39.8 years, received quinidine at 439 milligrams per day for 5.0 years. Therapy was stopped in three cases or 6% for side effects. Quinidine reduced by 26% the risk of experiencing life-threatening arrhythmic events in cases versus controls; hazard ratio, 0.74; P equals 0.62. In 27 of 123 Brugada Syndrome patients symptomatic for life-threatening arrhythmic events who were treated for 7.0 years, the annual rate of life-threatening arrhythmic events decreased from 14.7% while off-quinidine to 3.9% while on-quinidine, P equals 0.03. The authors noted that recurrent life-threatening arrhythmic events were recorded in 4 or 15% of cardiac arrest survivors while on-quinidine, underscoring the importance of implantable defibrillator therapy.

                                                That's it for this month. We hope that you will find the Journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.