Circulation: Arrhythmia and Electrophysiology October 2019 Issue

Circulation: Arrhythmia and Electrophysiology On the Beat

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 paper, in a single‐center observational cohort study, Owen Donnellan and Associates compared arrhythmia recurrence rates in morbidly obese patients who underwent prior bariatric surgery, with those of non-obese patients following atrial fibrillation ablation. In addition to morbidly obese patients who did not undergo bariatric surgery, they matched 51 morbidly obese patients' body mass index, 40 kilograms per meter squared, who had undergone prior bariatric surgery in a two to one manner with 102 non-obese patients, and 102 morbidly obese patients without bariatric surgery on the basis of age, gender, and timing of atrial fibrillation ablation. From the time of bariatric surgery to ablation, bariatric surgery was associated with a significant reduction in BMI. 47.6 to 36.7 and reduction in systolic blood pressure, 145 to 118, P < 0.001.

During a mean follow up of 29 months following ablation, recurrent arrhythmia occurred in 10 out of 51 or 20 patients in a bariatric surgery group, compared to 25 out of 102 patients, 24.5% in a non-obese group, and 56 out of 102 or 55% in the non-bariatric surgery morbidly obese group. No procedural complications were observed in the bariatric surgery group. In our next paper, Martin Andreas and Associates examined whether noninvasive, low-level, transcutaneous electrical stimulation of the greater auricular nerve reduced the risk of postoperative atrial fibrillation, in a pilot of patients undergoing cardiac surgery. After cardiac surgery, electrodes were applied in the triangular fossa of the ear. Stimulation, amplitude 1-million-amp frequency, one Hertz for 40 minutes, followed by a 20-minute break, was performed for up to two weeks after cardiac surgery. Patients were randomized into sham, N equals 20 or treatment group, N equals 20, for low- level, transcutaneous electrical stimulation. Patients receiving low-level, transcutaneous stimulation had a significant reduced incidence of postoperative atrial fibrillation. Four out of 20, compared to controls 11 out of 20. P equals 0.02.

The median duration of postoperative atrial fibrillation was comparable between the treatment group and control group. No effect on low-level stimulation on CRP or IL-6 levels was detectable. In our next paper, Kazuki Iso and Associates examine whether the vagal response phenomenon is common to patients without atrial fibrillation. Continuous, high- frequent stimulation of the left atrial ganglion and plexus was performed in 42 patients, undergoing ablation for atrial fibrillation. In 21 patients undergoing ablation for left-sided accessory pathway, the high frequency stimulation, 20 Hertz at 25 milliamps of 10 millisecond pulse duration, was applied for five seconds at three sites within the presumed anatomical area of each of the five major left atrial ganglion plexus, for a total of 15 sites per patient. The authors define vagal response to high frequency stimulation, as prolongation of the R interval by > 50% in comparison to the mean pre-high-frequency stimulation RR interval, average over 10 beats.

In active ganglion plexus areas, is areas in which vagal response was elicited. Overall, more active ganglion plexi or GP areas were found in the atrial fibrillation group patients, than in the non-atrial fibrillation group patients. And in all five major GPS, the maximum R interval during high-frequency stimulation was significantly prolonged in atrial fibrillation patients. After multivariate adjustment, association was established between the total number of vagal response sites and the presence of atrial fibrillation. The authors concluded that the significant increase in vagal responses elicited in patients with atrial fibrillation, compared to responses in non-atrial fibrillation patients, suggests that the vagal responses is to hypercan stimulations, reflect an abnormally increased ganglion plexi activity, specific to atrial fibrillation substrates.

In our next paper, Vidal Essebag and Associates combine the data from the Bruise Control One and Two studies to evaluate the effect of concomitant antiplatelet therapy on clinically significant hematomas, and to understand the relative risk of clinically significant hematomas in patients treated with DOAC versus continued Warfarin. The Bruise Control study demonstrated that perioperative Warfarin continuation, reduced clinically- significant hematomas by 80%, compared to Heparin bridging. 3.5% versus 16%. Bruise Control Two observed a similarly low risk of clinically-significant hematomas when comparing continued versus interrupted direct oral anticoagulant. 2.1% in both groups. A total of 1,343 patients were included in Bruise Control One and Bruise Control Two, the primary outcome for both trials with clinically-significant hematomas. There are 408 patients identified as having continued either a single or dual antiplatelet agent at the time of device surgery. Anti-platelet use versus non-use was associated with clinically-significant hematomas in 9.8% versus 4.3%. P less than 0.001 and remained a strong independent predictor with multi-variate adjustment. Odds ratio 1.965, however, multivariate analysis adjusting for anti-platelet use, there was no significant difference in clinically-significant hematomas observed between direct oral anticoagulant use, compared with continued Warfarin.

In our next paper, Markus Rottmann and associates examine the relationship between activation slowing during sinus rhythm, and vulnerability for reentry, and correlated the areas with components of the circuit. In a porcine model of healed infarction, of 15 swine, nine had inducible ventricular tachycardia, 5.2 per animal. While in six swine, VT could not be induced despite stimulation from four RV and LV sites at two drive trains in six extra stimuli down to refract refractoriness. Infarcts with ventricular tachycardia had a greater magnitude of activation slowing, during sinus rhythm, a minimal endocardial activation velocity cutoff, less than 0.1 meters per second. Differentiated inducible from non-inducible infarctions. P equals 0.15. Regions of maximal endocardial slowing during the sinus rhythm corresponded to the VT isthmus. Area under the curve equals 0.84 while bystander sites exhibited near normal activation during sinus rhythm. VT circuits were complex, with 41.7 exhibiting discontinuous propagation with intramural bridges of slow conduction in delayed quasi -simultaneous endocardial activation. Regions forming the VT isthmus borders had facts or activation during sinus rhythm, while regions forming the inner isthmus were activated faster during ventricular tachycardia.

In our next paper, Mary Rooney and Associates sought to define the prevalence of subclinical atrial fibrillation in a community-based elderly population, and to characterize subclinical atrial fibrillation and the incremental diagnostic yield of four versus two weeks of continuous ECG monitoring. They conducted a cross-sectional analysis within the community- based, multi-centered observational atherosclerosis risk in communities. Erik Study, using visit five, 2016 to 2017 data. The 2,616 Erik Study participants who wore a lead-less ambulatory ECG monitor for up to two weeks were age 79 years, 42% men and 26% black. In its subset, 386 participants without clinically-recognized atrial fibrillation wore the monitor twice, each time for two weeks. They characterize the prevalence of subclinical atrial fibrillation, atrial fibrillation detected without clinically recognized atrial relation. Over two weeks of monitoring and the diagnostic yield of four versus two weeks, the authors found that the prevalence of subclinical atrial relation was 2.5%. the prevalence of subclinical each relation was 3.3% among white men, 2.5% among white women, 2.1% among black men and 1.6% among black women.

Subclinical A Fib was mostly intermittent, 75%. Among those with intermittent subclinical atrial fibrillation, 91% had an AF burden of less than or equal to 10%, during the monitoring period. In a subset of 386 patients without clinical atrial fibrillation, 78% more subclinical atrial fibrillation was detected by four weeks versus two weeks of ECG monitoring. In this study, the prevalence of subclinical A Fib was lower than previously reported. And monitoring beyond two weeks provided substantial incremental diagnostic yield.

In our next study, Rafael Ramirez and Yoshio Takemoto and Associates investigated arrhythmic mechanisms of Ranolazine in sheet models, in paroxysmal and persistent atrial fibrillation. Paroxysmal atrial fibrillation was maintained during acute stretch and persistent atrial relation was induced by long-term atrial tachypacing. Isolated Langendorff-perfused sheet parts were optically mapped. In paroxysmal atrial fibrillation, Ranolazine 10 micromolar reduced dominance frequency from 8.3 to 6.2 Hertz. P less than 0.01, before converting to sinus rhythm, decreased singularity point density for 0.07 to 0.039 and left atrial epicardium and prolonged atrial fibrillation cycling. Road or duration tip trajectory in variants of Afib cycle lengths were unaltered. In persistent atrial fibrillation, Ranolazine reduced dominance frequency, prolonged atrial fibrillation cycle length, increased the variance of atrial fibrillation cycling and had no effect on singularity point density, and failed to convert atrial fibrillation to sinus rhythm. Doubling the Ranolazine concentration or supplementing with Dofetilide failed to convert persistent atrial fibrillation to sinus rhythm.

In computer simulations or rotors, reducing the sodium current decreased dominant frequency, increased tip meandering, and produce vortex shedding upon wave interaction with un-excitable regions. Thus, the authors concluded that paroxysmal atrial fibrillation and persistent atrial relation respond differently to Ranolazine. Cardioversion in the paroxysmal atrial fibrillation can be attributed partly to decrease dominant frequency and singularity point density and prolongation of atrial fibrillation cycling. In persistent atrial fibrillation, increased dispersion of atrial-like cycle length and likely vortex shedding, contributes to rotor formation, compensating for any rotor loss, and may underline the inefficacy of Ranolazine to terminate persistent atrial fibrillation.

In our next paper, Pyotr Platonov and Associates assess the risk of atrial fibrillation and its relationship to Long-QT syndrome genotype, and the long-term prognosis in Long-QT syndrome patients. Genotype- positive patients with Long-QT syndrome. 784 with LQT1. 746 with LQT2, and 233 with LQT3, were compared with 2043 genotype-negative family members. In patients followed from birth to 60 years, LQT3 patients had an increased risk of atrial fibrillation compared to genotype-negative family members. Hazard ratio 6.62. While neither LQT1 or LQT2 demonstrated increased atrial fibrillation risk. After the age of 60 years, LQT2 patients had significant lower risk of atrial fibrillation compared with genotype-negative controls. Hazard ratio of 0.07. Atrial fibrillation was a significant predictor of cardiac events in LQT3 patients, through the age of 60. Hazard ratio, 5.38. The authors concluded that there's an increased risk of early-age atrial fibrillation in LQT3 patients and a protective effect of LQT2 genotype, resulting in a decreased risk of atrial fibrillation after the age of 60.

In our next paper, Julia Ramírez and Associates evaluated the cardiovascular prognostic value of T-waves morphology restitution in 55,222 individuals undergoing an exercise stress test in the UK biobank, and identify any genetic contribution. They found that 1,743 or 3.2% of individuals had a cardiovascular event. T-wave morphology restitution during recovery from exercise was significantly associated with cardiovascular events. Hazard ratio 1.11. Independent of clinical variables and other ECG markers, T-wave morphology restitution during recovery from exercise was also associated with all-cause mortality. Hazard ratio 1.1. And ventricular arrhythmias, hazard ratio 1.16. They identified 12 genetic loci, in total for T-wave morphology restitution during exercise, in T wave morphology restitution during recovery, of which nine are associated with another ECG marker. Individuals with the top 20% of T-wave morphology restitution during recovery, genetic risk scores, were significantly more likely to have a cardiovascular in the full UK biobank. 5.3% than individuals in the bottom percent, a 20% hazard ratio of 1.07.

We have two other research letters in a special report. Wassim Mosleh, Sharma Kattel report that Galectin-3 is a predictor of mortality after cardiac arrest. In the next research letter, Jerry Jez and Associates report on remotely-navigated ablations in ventricular myocardium, that result in acute lesion-size, comparable to force sensing manual navigation. In a special report, Sohaib Virk and Saurabh Kumar report on a meta-analysis of remote magnetic versus manual catheter navigation for atrial fibrillation ablation. That's it for this month. We'll hope that you'll 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.