Circulation: Arrhythmia and Electrophysiology On the Beat May 2018

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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 study, Filip Plesinger and associates examined whether a computerized analysis of the body surface 12-lead ECG can be used to measure the ventricular electrical activation delay as a predictor of heart failure or death following resynchronization therapy in a MADIT-CRT trial.

The authors found that left bundle branch block patients with baseline ventricular electrical activation delay less than 31.2 milliseconds had a 35% risk of MADIT-CRT endpoints, while patients with ventricular electrical activation delay greater than or equal to 31.2 milliseconds had a 14% risk, P value of less than 0.001.

The hazard ratio for predicting primary endpoints in patients with low ventricular electrical activation delay was 2.34 with a P value of less than 0.01. However, ventricular electrical activation delay was not predicted in patients with right bundle branch block or IVCD.

In our next study, Karl-Heinz Kuck and associates examined the predictors of long-term clinical outcomes after catheter ablation of atrial fibrillation in 750 patients in the FIRE AND ICE Trial. Using propensity score stratification methods to count for differences in baseline characteristics between sexes, the authors found that female sex with a hazard ratio of 1.37, P equals 0.01, and prior direct current cardioversion with a hazard ratio of 1.40, P equals 0.013 were independently associated with atrial fibrillation recurrence.

Female sex with hazard ratio of 1.36, P value of 0.035 and hypertension with a hazard ratio of 1.48, P value of 0.013 independently predicted cardiovascular rehospitalization. A longer history of atrial fibrillation with a hazard ratio of 1.03, P value of 0.039 increased the rate of repeat ablation.

After propensity score adjustment, women continued to have higher rates of primary efficacy failure with adjusted hazard ratio of 1.51, P less than 0.05 and cardiovascular rehospitalization with a hazard ratio of 1.40, P less than 0.05.

In the next study, Laura Bear and associates examined the reliability of inverse electrocardiographic mapping of cardiac electrical activity from recorded body surface potentials. In five anesthetized closed-chest pigs, torso and ventricular epicardial potentials were recorded simultaneously during sinus rhythm, epicardial, and endocardial ventricular pacing. Two approaches, coupled finite/boundary element methods and a meshless approach based on the method of fundamental solutions, were compared.

The authors found that inverse mapping underestimated epicardial potentials more than twofold, P less than 0.0001. Mean correlation coefficients for reconstructed epicardial potential distributions ranged from 0.60 to 0.64 across all methods. Epicardial electrograms were recovered with reasonable fidelity at approximately 50% of the sites, but variation was substantial.

General activation spread was reproduced with a mean correlation coefficient of 0.72 to 0.78 for activation time maps with spatio-temporal smoothing. Epicardial foci were identified with a mean location error approximately 16 millimeters. Inverse mapping with method of fundamental solutions was better than coupled finite/boundary element methods.

The authors concluded that spatio-temporal variability of recovered electrograms may limit the resolution, with implications for accuracy of arrhythmia localization.

In the next study, Pejman Raeisi-Giglou and colleagues examined the incidence of pulmonary vein stenosis in 10,368 patients undergoing atrial fibrillation ablation from 2000 to 2015. Computed tomography scans were performed three to six months after the procedures. Severe pulmonary vein stenosis was observed in 52 patients, or 0.5%. The left superior pulmonary vein represented 51% of all severely stenosed veins.

Percutaneous interventions were performed in 43 patients, and complications occurred in five, including three pulmonary vein ruptures, one stroke and one phrenic injury. Over a median follow-up of 25 months, 41, or 79%, of patients remained arrhythmia-free.

In our next paper, Koichi Nagashima and associates compared hot balloon ablation and cryoballoon ablation in a 165 consecutive patients who underwent initial atrial fibrillation catheter ablation. Of the 165 patients, 74 propensity score-matched patients equally divided between hot balloon ablation and cryoballoon ablation were studied.

Patients' characteristics included age, sex, body mass index, atrial fibrillation subtype, CHA2DS2-VASc score, and left atrial dimension were similar between the two groups. 52% of the hot balloon ablation patients required touch-up with radiofrequency ablation for residual/dormant pulmonary vein conduction versus 24% of the cryoballoon ablation patients with a P value of 0.02.

The anterior aspect of the left superior pulmonary vein was the site in 41% of the touch-ups after hot balloon versus the inferior aspect of the inferior pulmonary veins in 22% of the touch-ups after cryoballoon ablation. Hot balloon lesions were smaller with an area of 23.8 centimeters squared compared to cryoballoon ablation lesions having an area of 33.5 centimeters squared with a P value of 0.0007. Within 12 months, both methods had an AF recurrence of 16%.

In our next paper, Mildred Opondo and associates randomized 61 patients, mean age 52 years, to either 10 months of high intensity exercise or yoga. The authors found that left atrial volume, Vo2 max, and left ventricular end-diastolic volume increased in the exercise group with no change in the control with a P value of less than 0.0001.

The authors did not find significant changes in atrial electrical activity and hypothesized that a longer duration training may be required to induce electrical changes.

In our next paper, because there's evidence that the distal part of the ligament of Marshall might be a sympathetic conduit between the left stellate ganglion and the ventricles, Shan Liu and associates randomly divided 29 dogs into a sham ablation group, a ligament of Marshall ablation group, and a left stellate ganglion ablation group. Ablation was performed before occlusion of the left anterior coronary artery.

Ligament of Marshall ablation attenuated blood pressure elevation induced by left stellate ganglion stimulation. Both ligament of Marshall ablation and left stellate ganglion ablation similarly prolonged ventricular refractory period and reduced the incidence of ventricular arrhythmias compared with sham ablation.

In our next study, Smith and Tester and associates examined the heterologous functional validation studies of putative long-QT syndrome subtype 2, LQT2, associated variants. Genetic testing of 292 sudden infant death syndrome cases identified nine KCNH2 variants, while some of the channels associated the variants can lead to accelerated deactivation and activation gating. Other current levels were similar to wild-type.

The authors examined the electronic health records of patients who were genotype positive for these particular sudden infant death syndrome–linked KCNH2 variants and found all of them had a median heart rate–corrected QT intervals less than 480 milliseconds and none had been diagnosed with long-QT syndrome or suffered cardiac arrest.

Simulating the impact of dysfunctional gating variants using computational models of the human ventricular action potential predicted that they have little impact on action potential duration. The authors concluded that these rare Kv11.1 missense variants are not long-QT2 causative variants and, therefore, do not represent the pathogenic substrate for sudden infant death syndrome in the variant-positive infants.

In our next study, Tina Baykaner and associates performed a systematic literature review and meta-analysis to determine outcomes from ablation of atrial fibrillation drivers in addition to pulmonary vein isolation or as a stand-alone procedure. The authors found 17 studies with a cohort size of 3,294 patients.

Atrial fibrillation driver ablation, when added to a pulmonary vein ablation or a stand-alone procedure compared the controls, produced an odds ratio of 3.1 with a P value of 0.02 for freedom from atrial fibrillation and an odds ratio of 1.8 with a P value of less 0.01 for freedom of all arrhythmias in four controlled studies.

Adding atrial fibrillation driver ablation to pulmonary vein ablation resulted in a freedom from atrial fibrillation of 72.5%, P value of less than 0.01 and a freedom from all arrhythmias of 57.8% with a P value less than 0.01. Atrial fibrillation termination was 40.5% and predicted favorable outcome from ablation with a P value of less than 0.05. Large multicenter randomized trials are needed to precisely define the benefits of adding driver ablation to a pulmonary vein isolation.

In our next study, Hidekazu Kondo and associates found that the adverse atrial remodeling, including atrial inflammation, lipidosis and fibrosis, were induced in both wild-type and Interleukin-10 knockout mice by high fat diet, but the effects were exaggerated in the Interleukin-10 knockout mice. Vulnerability to atrial fibrillation was also significantly enhanced by the high fat diet.

The total amount of epicardial and pericardial adipose tissue volume was increased with high fat diet. Proinflammatory and profibrotic cytokines of epicardial and pericardial adipose tissue were also upregulated. In contrast, the protein level of adiponectin was downregulated by the high fat diet. Systemic Interleukin-10 administration markedly ameliorated the high fat diet induced obesity-caused left atrial remodeling and vulnerability to atrial fibrillation.

The authors concluded that Interleukin-10 treatment may limit the progression of atrial fibrillation occurring in the setting of a high fat diet.

In our next paper, Garcia and Campbell and associates demonstrated the ability to deliver amiodarone epicardially over a sustained period of time. The authors demonstrated in a pig model of atrial fibrillation that an amiodarone containing polyethylene glycol-based hydrogel placed directly on the atrial myocardium in a minimally invasive catheter procedure significantly reduced the duration of sustained atrial fibrillation at 21 and 28 days. The authors found that inducibility of atrial fibrillation was also reduced.

In our final paper, Htet Khine and associates examined the effect of spaceflight on the changes in atrial structure, supraventricular beats, and atrial electrophysiology, and to determine whether spaceflight could increase the risk of atrial fibrillation.

The authors found that, in 13 that in astronauts, the left atrial volume transiently increased after six months in space without changing atrial function. Right atrial size remained unchanged, while one astronaut had a very large increase in supraventricular ectopic beats, none developed atrial fibrillation. The P-wave amplitude duration did not change over time, but RMS 20 decreased on all fight days except landing day.

That's it for this month. Thanks for listening to On the Beat. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next month.

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