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, Danielle Haanschoten, Hein Wellens and Associates aim to examine survival benefit of prophylactic implantable cardioversion defibrillator (ICD) implantation in early selected high-risk patients with primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). A randomized, multicenter, controlled trial compared ICD versus conventional medical therapy in high-risk primary PCI patients based on one of the following factors: Left ventricular ejection fraction (LVF) less than 30% within four days of STEMI, primary ventricular fibrillation, Killip class 2 or greater and/or TEMI flow less than three after PCI. ICD was implanted 30 to 60 days after MI, myocardial infarction, primary endpoint was all cause mortality three years of follow-up. The trial was prematurely ended after inclusion of 266 patients, 38% of the calculated sample size. Additional survival assessments was performed in February 2019 for the primary endpoint. A total of 266 patients, 78.2% male with a mean age of 60.8 years were enrolled. 131 were randomized to the ICD arm and 135 patients to the control arm. All cause mortality was significantly lower in the ICD group, five versus 13, hazard ratio of 0.37 after three years follow-up. Appropriate ICD therapy occurred in nine patients at three years follow-up, 5 within the first eight months after implantation. After median long-term follow-up of nine years, total mortality (18% versus 38%, hazard ratio of 0.58) and cardiac mortality (hazard ratio of 0.52) was significantly lower in the ICD group. Non-cardiac death was not significantly different between the groups. LVEF increased 10% or more in the 46.5% of patients during follow-up and the extent of improvement was similar in both study groups. The authors concluded that in this prematurely terminated and thus underpowered randomized trial early prophylactic ICD implantation demonstrated lower total and cardiac mortality in high-risk STEMI patients treated with primary PCI.

In our next paper Felipe Bisbal, Eva Benito and Associates aim to test the efficacy of ablating, cardiac magnetic resonance, CMR detected atrial fibrosis plus pulmonary vein isolation (PVI). This was an open label, parallel group, randomized controlled trial. Patients with symptomatic drug refractory AF paroxysmal or persistent undergoing first or repeat ablation were randomized one-to-one basis to receive PVI plus CMR-guided fibrosis ablation, the CMR group or PVI alone, the PVI alone group. The primary endpoint was a rate of recurrence greater than 30 seconds at 12 months of follow-up using a 12-lead ECG and Holter monitoring at 3, 6 and 12 months. The analysis was conducted by intention to treat. In total 155 patients, 71% male, age 59, CHADS2-VASc 1.3, 54% paroxysmal AF were allocated to the PVI group alone (n=76) or CMR group(n=79). First ablation was performed in 80% and 71% in the PVI alone and CMR groups respectively. The mean atrial fibrosis burden was 12%, only approximately 50% of patients had fibrosis outside the pulmonary vein area. 100% and 99% of patients received the assigned intervention in the PVI alone and CMR group. Primary outcome was achieved in 21 patients (27.6%) in the PVI alone group and 22 patients (27.8%) in the CMR group (Odds ratio 0.01, P=0.976). There was no differences in the rate of adverse events, three in the CMR group and two in the PVI alone group. The authors concluded that a pragmatic ablation approach targeting CMR detected atrial fibrosis plus PVI was not more effective than PVI alone in an unselected population undergoing AF ablation with low fibrosis burden.

In the next paper, Vivek Reddy and Associates tested a novel neuromodulation therapy of stimulation of epicardial cardiac nerves passing along the posterior surface of the right pulmonary artery. 15 subjects admitted for defibrillator implantation (ejection fraction≤35%) on standard heart failure medications were enrolled. Through femoral arterial access, high fidelity pressure catheters were placed in the left ventricle and aortic root. After electro anatomic rendering of the pulmonary artery and branches, either a circular or basket electrophysiology catheter was placed in the right pulmonary artery to allow electrical intravascular stimulation at 20 hertz, 4 ms pulse width, and less than or equal to 20 milliamperes. Changes in the maximum positive dP/dt, the dP/dtMax indicated change in ventricular contractility. Of 15 enrolled patients, five were not studied due to equipment failure or abnormal pulmonary artery anatomy. In the remaining patients dP/dtMax increased significantly by 22.6%. There was also a significant increase in maximum negative dP/dt, dP/dtMin, mean arterial pressure, systolic pressure, diastolic pressure, and left ventricular systolic pressure. There was no significant change in heart rate or left ventricular diastolic pressure. In this first-in-human study, the authors demonstrated that in humans with stable heart failure, left ventricular contractility could be accentuated without an increase in heart rate or left ventricular filling pressures.

In our next paper, Jorge Romero, Luigi Di Biase, and Associates, in their study investigated the incremental benefit of left atrial appendage electrical isolation (LAAEI) in patients undergoing catheter ablation for nonparoxysmal atrial fibrillation (AF). Propensity score-matched analysis was performed using a prospective registry database from 2010 to 2014. All patients in the LAAEI group were matched based on baseline characteristics, echocardiographic parameters, and procedural ablation techniques. Authors identified 1842 patients who underwent catheter ablation for nonparoxysmal atrial fibrillation. Propensity score matching yielded 1092 patients, 546 with LAAEI, and 546 without LAAEI. At five years follow-up, overall freedom from all arrhythmia recurrence, off-antiarrhythmic drugs, in patients who underwent LAAEI was 68.9% versus 50.2% in those who underwent standard ablation (p<0.001). Acute complication rates were similar between groups, LAAEI 1.3% and non-LAAEI 0.73% (p=0.36). At five year follow-up, 382 (70%) patients in the LAAEI group remained on oral anticoagulation versus 217 (39.7%) in the non-LAAEI group. No thromboembolic events occurred in either group on oral anticoagulation. In patients who were off oral anticoagulation, a five year follow-up, thromboembolic events occurred in 15 of 164 (9.1%) in the LAAEI group and 4 out of 329 (1.2%) in the non-LAAEI group (p<0.001). The authors concluded that at five year follow-up, LAAEI was associated with significantly higher freedom from all atrial arrhythmia recurrence in patients with persistent and long-standing persistent AF without increasing acute procedural complication rate. In patients off oral anticoagulation, there appears to be a higher risk of thromboembolic events in the LAAEI group.

In the next paper, Niraj Varma and Associates postulated that left ventricular (LV) epicardial pacing results in slowly propagating pace wave fronts effect that may limit cardiac resynchronization therapy (CRT) efficacy in patients with left ventricular (LV) enlargement using conventional biventricular or bi-V pacing and single LV pacing, but may be mitigated by LV pacing by two widely spaced sites using MultiPoint pacing (MPP) with anatomic separation (AS) of 30 millimeters or more. They tested this hypothesis in the multi-centered MPT IDE trial. Following implant, quadripolar biventricular pacing was activated in all patients (n=506). From 3 to 9 months post implant among patients with available baseline LV and diastolic volumes LVEDV measures and 188 received bi-V pacing and 43 receiving MPP-AS. Patients were dichotomized by median baselines LVEDV indexed to height. Outcomes were measured by the clinical composite score (CCS) as the primary endpoint, quality of life, left ventricular remodeling, EF greater than 5% and systolic volume decreased 10% in heart failure event or cardiovascular death. LVEDVI median was 1.4 millimeters per centimeter. Baseline characteristics differed in patients with LVEDVI greater than median versus LVEDVI less than or equal to median. Among patients with LVEDVI greater than median, bi-V was less efficacious compared to patients with LVEDVIs less than or equal to median. Clinical composite scores 65% versus 79%. In contrast, MPP-AS programming generated greater composite score response (92% versus 65%, P=0.03) and improved quality of life (31 versus -15.7, P=0.38) versus bi-V pacing with LVEDV greater than median. Reverse remodeling trended better with MPP-AS programming. When LVEDVI was greater than median, heart failure event rate increased following the three months randomization point in bi-V but no heart failure event occurred in patients with MPP-AS programming between three and six months in LVEDVI greater than median. All measured outcomes did not differ in patients receiving MPP-AS and bi-V pacing with LVEDVI less than or equal to median. The authors concluded that conventional biventricular pacing even with a quadripolar lead has reduced efficacy in patients with left ventricular enlargement however in patients with larger hearts and programmed to MPP-AS the greatest response rate was observed.

In our next paper, Chih-Min Liu, Shih-Lin Chang, Hung-Hsun Chen and Associates, applied deep learning to pre-ablation pulmonary vein computed tomography (PVCT) geometric slices to create a predictive model for non-pulmonary vein (NPV) triggers in patients with paroxysmal atrial fibrillation (PAF). They retrospectively analyzed 521 PAF patients who underwent catheter ablation of PAF. Among