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, Zak Loring and associates examined 3,139 patients undergoing atrial fibrillation (AF) ablation, between 2016 and 2018 in the Get With The Guidelines-Atrial Fibrillation Registry from 24 US centers. Patients undergoing AF ablation were predominantly male (63.9%) and Caucasian (93.2%) with a median age of 65. Hypertension was the most common comorbidity (67.6%), and persistent atrial fibrillation patients had more comorbidities than paroxysmal AF patients. Drug refractory, paroxysmal AF was most common ablation indication (class I, 53.6%) followed by drug refractory, persistent AF (class I, 41.8%). Radio-frequency, RF ablation, with contact force sensing was the most common ablation modality (70.5%) and 23.7% of patients underwent cryoballoon ablation. Pulmonary vein isolation was performed in 94.6% of de novo ablations. The most common adjunctive lesion included left atrial roof or posterior/inferior lines and cavotricuspid isthmus ablation. Complications were uncommon (5.1%) and were life-threatening in 0.7% of cases.

In our next paper, Brian Howard and associates hypothesize that pulse field ablation (PFA) would reduce pulmonary vein stenosis risk and collateral injury compared to irrigated radiofrequency ablation (IRF). IRF and PFA deliveries were randomized in eight dogs with two superior pulmonary veins (PVs), ablated with using one technology and two inferior PVs ablated with the other technology. IRF energy (25-30 watts) or PFA with delivered (16 pulse trains) at each PV in a proximal and in a distal site. Contrast computed tomography (CT scans) were collected at 0, 2, 4 and 8, and 12 week, including termination time points to monitor PV cross-sectional area at each PV ablation site. Maximum average change in normalized cross-sectional area at 4 weeks was 46.1%±45.1% post IRF compared to -5.5±20.5% for PFA (P≤ to 0.001). Necropsy showed expansive PFA lesions without stenosis in the proximal PV sites compared to more confined and often incomplete lesions after IRF. At the distal PV sites only IRF ablations were grossly identified based on focal fibrosis. Mild pulmonary chronic parenchymal hemorrhage was noted in three left superior pulmonary vein lobes after IRF. Damage to vagus nerves, as well as evidence of esophagus dilation, occurred at sites associated with IRF. In contrast, no lung, vagal nerve, or esophageal injury was observed at PFA sites.

In our next paper, Mohamed Diab and associates aimed to assess the safety of ablation for atrial fibrillation (AF) with trans-esophageal (TEE) screening on intracardiac echocardiography (ICE) imaging of the appendage in direct oral anticoagulant (DOAC) compliant patients. They studied 900 patients with a medium CHA2DS2-VASc score of two. Interquartile range one to three. All consecutive patients presenting with AF or atrial flutter on DOAC were included. All were on DOACs (333 Rivaroxaban, 285 Dabigatran, 281 Apixaban and one Edoxaban). Thromboembolic complications occurred in four patients (0.3%), two ischemic strokes, one transient ischemic attack without residual deficit and one splenic infarct, all with no further complications. Bleeding complications incurred in 5 patients (0.4%), including 2 pericardial effusions (1 intraoperative, 1 after 30 days, both drained), and 3 groin hematomas (1 due to needing heparin for venous thrombosis, none requiring intervention). No patients required emergent surgeries.

In our next paper, Alexios Hadjis and associates aim to explore the role of complete diastolic pathway activation mapping on ventricular tachycardia (VT) recurrence. They studied 85 consecutive patients who underwent VT ablation using and guided by high-density mapping. During activation mapping, the presence of electrical activity in all segments of diastole defined the evidence of having had recorded the whole diastolic interval. Patients were categorized as having recorded the full diastolic pathway, partial diastolic pathway or no diastolic pathway map performed. Recurrences of VT were defined as appropriate IC therapies or on the basis of EC documented arrhythmia. Complete recording of the diastolic pathway was achieved in 36 of 85 (42.4%). Partial recording of the diastolic pathway of clinical VT was achieved in 24 of 85 (28.2%). No recording of the diastolic pathway of clinical VT was feasible in 25 of 85 patients (29.4%). At a mean of 12.8 months, freedom from VT recurrences was 67% in the overall cohort. At a mean of 12.8 months, freedom from VT recurrence was 88% in patients who had full diastolic activity recorded, 50% of partial diastolic activity recorded and 55% in those who underwent substrate modification (P=0.02). The authors concluded that mapping of the entire diastolic pathway was associated with a higher freedom from VT occurrence compared to partial diastolic pathway recording and substrate modification. The use of multielectrode mapping catheters in recording diastolic activity may help predict those VTs employing intramural circuits and further optimize ablation strategies.

In our next paper, Hui-Nam Pak and associates investigated whether electrical posterior box isolation (POBI) may improve rhythm outcome of catheter ablation in patients in whom persistent atrial fibrillation changes to paroxysmal atrial fibrillation after antiarrythmic drug medication and cardioversion. They prospectively randomized 114 patients, 75% male, 59.8 years old to circumferential pulmonary vein ablation (CPVI) alone (n=57) and an additional POBI group (n=57). Primary endpoint was AF recurrence after a single procedure, and secondary endpoints were recurrence pattern, cardioversion rate and response to antiarrhythmic drugs (AAD). After a mean follow-up of 23.8 months, the clinical recurrence rate did not significantly differ between the CPVI alone and additional POBI group (31.6% versus 28.1%; P=0.682). The recurrence rate as atrial tachycardias, 5.3% versus 12.3% (P=0.14) and cardioversion rates, 5.3% versus 10.5% (P=0.25) were not significantly different between the CPVI and POBI group. At the final follow-up, sinus rhythm was maintained without antiarryhthmic drug in 52.6% of CPVI group and 59.6% of the POBI group (P=0.45). No significant difference was found in major complications between the two groups, 5.3% versus 1.8% (P=0.618). But the total ablation time was significantly longer in the POBI group (4187 seconds versus 5337 seconds; P<0.001).

In our next paper, Dan Musat and associates assess the incidents and predictors of very late occurrence (VLR) when atrial fibrillation occurs 12 months or more after ablation in patients who underwent cryoballoon pulmonary vein isolation alone (PVI), had an ILR and were confirmed AF free (atrial fibrillation free) for at least one year. They included 188 patients, mean 66 years, 62% male and 54% paroxysmal atrial fibrillation with CHA2DS2-VASc 2.6. After one year post PVI, 49% of patients remained AF free. During subsequent follow-up, 32% had very late recurrence of atrial fibrillation. The only independent risk factor for very late recurrence was an elevated CHA2DS2-VASc score (hazard ratio 1.317; P=0.06). Patients with CHA2DS2-VASc score greater than four represented a quarter of the population and were at highest risk.

In our next paper, Daniele Pastori, Danilo Menichelli, Gregory Yip and associates in the ATHERO-AF Study Group investigate the association between family history of atrial fibrillation (AF) in cardiovascular events (CVEs), major adverse events (MACE), and cardiovascular mortality. They conducted a multicenter prospective observational cohort study, including 1,722 nonvalvular AF patients from February 2008 to August 2019 in Italy. Family history of AF was defined as the presence of AF in a first-degree relative: mother, father, sibling, or children. Primary outcome was a composite of CVEs, including fatal/non-fatal ischemic stroke and myocardial infarction and cardiovascular death. Second, they analyze the association with MACE. Mean age 74.6 years, 44% women. Family history of AF was detected in 368 or 21.4% of patients, and 3.5% had two or more relatives affected by AF. Age of AF onset progressively decreased from patients without family history of AF compared to those with single and multiple first-degree affected relatives (P<0.001). During a mean follow-up of 23.7 months or 4,606 patient years, 145 CVEs, that's 3.15% per year, 98 MACE (2.13% per year) and 57 cardiovascular deaths (0.9% per year) occurred. After adjustment for cardiovascular risk factors, family history of AF was associated with a higher risk of CVEs (hazard ratio. 1.524: P=0.039), MACE (hazard ratio 1.917; P=0.006) and cardiovascular mortality (hazard ratio 2.008; P=0.036). Subgroup analysis showed that this association was modified by age, sex, and prior ischemic heart disease. The authors concluded that in a cohort of elderly patients with high atherosclerotic burden, family history of AF was evident in more than 20% of patients and was associated with an increased risk of CVEs and mortality.

In our next paper, Louise Reilly and associates created the first patient-inspired KCNJ2 transgenic mouse and studied the effects of this mutation on cardiac function, IK1 and calcium handling to determine the underlying cellular arrhythmic pathogenesis. A cardiac specific KCNJ2-R67Q mouse was generated and bred for heterozygosity. That's R67Q+/-. Echocardiography was performed at rest and under anesthesia. In vivo electrocardiogram, ECG recording, and whole heart optical mapping of intact hearts was performed before and after adrenergic stimulation in wild-type littermates and R67Q+/- mice. In IK1 measurements and action potential AP characteriza