Circulation: Arrhythmia and Electrophysiology December 2019 Issue

Paul J. 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, Jacob Koruth and Associates examine the ability to produce ablation lesions using pulse field ablation, which is tissue specific and non-thermal in swine compared to radio frequency ablation. All 46 targeted veins were successfully isolated on the first attempt in all cohorts. Pulmonary vein isolation durability was assessed in 28 veins, including the SVC. Durability was higher in the pulsed field ablation bipolar group, 18 out of 20 in the bipolar group, 10 out of 18 in the monopolar group, and 3 out of 6 in the radio frequency group. P = 0.002. Transmit morality rates were similar across groups with evidence of nerve damage only with radiofrequency.

In our next paper, Vivek Reddy and Associates is part of the multicentered first-in-human study, RADIANCE, examine the ability of a novel compliant radio frequency balloon catheter with 10 irrigated flexible electrodes to simultaneously and independently deliver energy. At four sites, 39 patients with paroxysmal atrial fibrillation underwent pulmonary vein isolation using energy delivery simultaneously from all electrodes up to 30 seconds posteriorly, and 60 seconds anteriorly. 152 of 152 targeted pulmonary veins were isolated. 79.6% with a single application. Electrical reconnection occurred in only 7 out of 150 pulmonary veins or 4.7% upon adenosine isoproterenol challenge. Esophageal temperature was monitored in all patients. The esophagus was also mechanically deviated in ten patients. At three months, imaging revealed no pulmonary vein stenosis and early atrial recurrence occurred in only 10 out of 39 or 25.6% of patients.

In our next paper Takeshi Kitamura and Associates examine the effect of substrate based ventricular tachycardia ablation targeting local abnormal ventricular activity on recurrent ventricular fibrillation events in patients with structural heart disease. In a retrospective two center study of a total of 686 patients with incident ventricular tachycardia ablation procedure targeting local abnormal ventricular activity, 21 patients, age 57 years left ventricular ejection fraction 30%, had both ventricular tachycardia and ventricular fibrillation.

A total of 80 ventricular fibrillation events were recorded in the ICD logs, the six months preceding ablation. Complete and partial local abnormal ventricular activity elimination was achieved in 11 or 52%, in 10 or 58% of patients respectively. Catheter ablation was associated with a highly significant reduction in ventricular fibrillation recurrences. P less than 0.0001 which were limited to three or 14 patients at six months. The total number of ventricular events therefore, decreased from 80 to three with a median of 1.0 to 0.0 in the six months prior to and following ablation respectively.

The reduction in ventricular fibrillation events was significantly greater in patients with catheter ablation compared to 21 match controls during a 6- month period preceding and following a baseline assessment. The authors concluded that substrate guided ventricular tachycardia ablation, targeting local abnormal ventricular activity, may be associated with a significant reduction in recurrent ventricular fibrillation, suggesting that ventricular tachycardia and ventricular fibrillation share overlapping arrhythmogenic substrate in patients with structural heart disease.

In our next paper, Feng Hu and Associates examine the effect of right anterior ganglion aided plexi ablation on vagal response during circumferential pulmonary vein isolation. 80 patients with paroxysmal atrial fibrillation who underwent first time ablation were prospectively enrolled and randomly assigned to two groups. Group A (n = 40) circumferential pulmonary vein isolation starting with the right pulmonary veins at the right anterior ganglion plexi site. In group B (n = 40) circumferential pulmonary vein isolation starting with the left pulmonary veins first, and the last ablation site being the right anterior ganglionic plexi site.

During circumferential pulmonary vein isolation, the positive vagal response was observed in only one patient in group A, in 25 patients in group B. P less than 0.001. A total of 21 patients with positive vagal response in group B needed temporary ventricular pacing during the procedure, while the only patient with positive vagal response in group A did not need temporary ventricular pacing, P less than 0.001. Compared with baseline basic cycle length, sinus node recovery time, and AV node Wenckebach pacing cycle length were decreased significantly after pulmonary vein isolation procedure in both groups, all P less than 0.05 and without differences between the two groups.

In our next paper, Karl-Heinz Kuck and Associates reported the results of the randomized atrial fibrillation management and congestive heart failure with ablation, AMICA trial. Patients with persistent or long standing persistent atrial fibrillation and left ventricular ejection fraction ≤ 35%, were randomly allocated to catheter ablation of atrial fibrillation or best medical therapy. The primary study endpoint was the absolute increase in left ventricular ejection fraction from baseline at one year. Pulmonary vein isolation was the primary ablation approach. Best medical therapy comprised rate or rhythm control. All patients were discharged after index hospitalization with a cardioverter defibrillator or resynchronization therapy defibrillator implanted.

This study was terminated early for futility of 140 patients, 65 years, 90% men available for endpoint analysis, 68 and 72 patients were assigned to ablation in best medical therapy respectively. At one year, left ventricular ejection fraction had increased in ablation patients by 8.8% and in medical therapy by 7.3%, P = 0.36. Sinus rhythm was recorded on 12-lead electrocardiograms at 1 year. In 61 of 83 ablation patients, or 73.5%, and 42 out of 82 best medical therapy patients or 50%. Device-recorded atrial fibrillation at one year, was 0% or maximally 50% of the time in 28 of 39 ablation patients, so 72% in 16 out of 36 best medical therapy patients or 44%. There were no differences in secondary endpoint outcomes of six-minute walk tests, quality of life or NT pro BNP between the ablation and best medical therapy patients.

In our next paper, Dhanunjaya Lakkireddy and Associates examined the association between unrecognized inflammation and premature ventricular contraction. In a single-center prospective study, 107 patients with 5,000 or more PVCs per 24 hours, which were symptomatic, and no known ischemic heart disease, underwent combination of laboratory testing including FDG or 18F-fluorodeoxyglucose pet scan, cardiac magnetic resonance imaging, and biopsy. The mean age cohort was 57 years, 41% were males, a left ventricular ejection fraction was 47%. Positive pet scan was seen in 51%, and 51% had preserved left ventricular function.

Based on clinical profile, FDG pet imaging, cardiac magnetic resonance imaging, and histological data, 58% received immunosuppressive therapy alone and 25% received immunosuppressive therapy and catheter ablation. Optimal response was seen in 67% over a mean follow-up of six months in patients with left ventricular systolic dysfunction, 37% showed a mean improvement in left ventricular ejection fraction of 13%.

In our next paper, Clare Atzema and Associates examined the association of rapid (3 days), early (7 days), and basic (30 days), outpatient physician follow-up with short and long-term outcomes in atrial fibrillation patients discharged from an emergency department. In 163 emergency departments in Ontario, Canada with a diagnosis of atrial fibrillation, they use landmark analysis with propensity score matching. In the 10,657 patients with rapid follow-up care who are propensity score matched to a patient with follow-up between 4 and 7 days, the hazard of a return emergency visit was reduced by 11%. In the 17,234 patients with early follow-up who are matched to a patient with care between 8 and 30 days, the 1-year mortality was 11% lower, and 1-year hospitalization was 6% lower.

Relative to no 30-day care, basic follow-up care was associated with an increased hazard ratio of 90-day hospitalization, but no longer was associated with mortality. The authors concluded that compared to follow-up care between 8 and 30 days, follow-up care within a week after discharge from an emergency department with atrial fibrillation, was associated with a reduction in death, in hospitalization at 1 year, in association not present with 30-day follow-up.

In our next paper, James Freeman and Associates evaluate outcomes including death, myocardial infarction, stroke or systemic embolism, intracranial bleeding, major bleeding hospitalization in patients undergoing atrial fibrillation ablation compared with a propensity score match cohort of patients treated with anti-arrhythmic medications only in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) I and II registries.

Among 21,595 patients, 6% underwent de novo atrial fibrillation ablation. The propensity score matched cohort included 1087 patients who underwent atrial fibrillation matched one-to-one with 1087 patients treated with an antiarrhythmic medication only. There were no significant differences in the risk of all-cause and cardiovascular death in most other major cardiovascular and neurologic events. Atrial fibrillation catheter ablation was associated with an increased risk of all cause hospitalization hazard ratio 1.24 particularly in the 3 months after the procedure. Among those who underwent atrial relation ablation with CHA₂DS₂ VAS score, 2 for men and 3 for women, 23% had oral anticoagulation discontinued after ablation. Among those with discontinue oral anticoagulation, the median time to discontinuation was 6.2 months. Thus, the authors found no difference in adjusted rates of cardiovascular and all-cause death, between patients treated with atrial fibrillation catheter ablation and antiarrhythmic medications only.

In our next paper, Michael Liu and Associates examined R-from-T as a common mechanism of arrhythmia initiation in long QT syndrome. In their study, spontaneous initiation of polymorphic ventricular tachycardia was elicited by gradually ramping up ICa,L to simulate the early phase of sympathetic surge or changing the heart rate, reproducing the different genotype-dependent clinical electrocardiographic features in LQTS type 2 and 3, T-wave alternans was observed followed by premature ventricular complexes. Compensatory pauses occurred resulting in short-long sequences, as ICa,L increased further polymorphic ventricular tachycardia episodes occurred, always proceeded by short-long-short sequences.

However, in LQTS type 1 once a PVC occurred, it almost immediately led to an episode of polymorphic ventricular tachycardia. Arrhythmias in LQT2 and 3 were bradycardia dependent, whereas LQT1 was not. In all 3 genotypes, PVCs always originated spontaneously from the steep repolarization gradient region and manifested on ECG as R-on-T. the authors called this mechanism R-on-T to distinguish it from the classic explanation of R-on-T arrhythmogenesis when an exogenous PVC coincidentally encounters a repolarization region. In R-from-T, the PVC and the T wave are causally related, where the steep repolarization gradients combine with enhanced ICa,L leading to the PVCs emerging from the T wave. Since enhanced ICa,L  was required for R-from-T to occur, suppressing window ICa,L  effectively prevented arrhythmias in all 3 genotypes.

In our next paper, Dhani Dharmaprani and Associates hypothesized phase singularity formation and destruction in fibrillation could be modeled as a self-regenerating Poisson renewal processes, producing exponential distributions of inter event times governed by constant rate parameters defined by prevailing properties of each system. The authors studied 5 systems, human persistent atrial fibrillation in 20 cases, tachypaced atrial fibrillation in sheep in 5 cases, rat atrial fibrillation in 4 cases, and rat ventricular fibrillation in 11 cases, as well as computer simulated fibrillation.

Phase singularity time to event data were fitted by exponential probability distribution functions computed using maximum entropy theory, and rates of phase singularity formation and destruction were determined. A systematic review is conducted to cross validate with sources from the literature. In all systems phase singularity lifetime and inter formation times were consistent with underlying Poisson renewal processes. The authors conclude that Poisson renewal theory provides an evolutionarily preserved universal framework to quantify formation and destruction of rotational events in cardiac fibrillation.

In our issue, there was a very interesting special report on hypothermia outcomes after transvenous lead extraction complications requiring cardiothoracic surgery by Peter Hu and Associates. In addition, there is a very interesting review of atrial fibrillation mediated cardiomyopathy by Kevin Heist and Associates.

That's it for this month. We 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.