Circulation: Arrhythmia and Electrophysiology On the Beat

Paul J. Wang, MD
  • 3.5 (11)
  • NATURAL SCIENCES

Each podcast will include key highlights from the journal's current issue and a report on new research published in the field of arrhythmia and electrophysiology.

  1. 01/13/2021

    Circulation: Arrhythmia and Electrophysiology November 2020 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, 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  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 them, PVCT geometric slices from 358 nonrecurrent AF patients one to three millimeters interspace per slice, 20 to 200 slices per each patient, ranging from the upper border of the left atrium to the bottom of the heart, for a total of 23,683 images of slices were used in the deep learning process, the ResNet34 of the neural network, to create the predictive model of the NPV trigger. There were 298 (83.2%) of patients with only pulmonary vein (PV) triggers and 60 (16.8%) with non-PV triggers plus or minus PV triggers. The patients were randomly assigned to either training, validation, or test groups, and their data was allocated according to those datasets. The image datasets were split into training (N=17,340), validation 3491, and testing 2852 groups, which had completely independent set of patients. The accuracy of prediction in each PVCT image for non-pulmonary vein trigger was 82.4%. The sensitivity and specificity were 64.3% and 88.4%, r

    46 min
  2. Circulation: Arrhythmia and Electrophysiology October 2020 Issue

    01/12/2021

    Circulation: Arrhythmia and Electrophysiology October 2020 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, Bruce Wilkoff and associates evaluated antibacterial envelope cost effectiveness compared to standard of care infection prevention strategies in the US healthcare system. Decision tree model was used to compare costs and outcomes of the antimicrobial envelope used adjunctive to standard of care infection prevention versus standard of care alone over a lifelong time horizon. The analysis was performed from an integrated payer provider network perspective. Infection rates, antimicrobial envelope effectiveness, infection treatment costs and patterns, infection related mortality and utility estimates were obtained from the WRAP-IT study. Life expectancy and long-term costs associated with device replacement, follow-up, and healthcare utilization were sourced from the literature. Costs and quality life adjusted years were discounted at 3%. An upper willingness-to-pay threshold of $100,000 per quality adjusted life year was used to determine cost-effectiveness in alignment with the American College of Cardiology and American Heart Association practice guidelines and as supported by the World Health Organization and contemporary literature. The base case incremental cost-effectiveness ratio (ICER) of the antibacterial envelope compared with standard-of-care was $112,603 per quality-adjusted life year. The ICER remained lower than the threshold in 74% of iterations in the probabilistic sensitivity analysis and was most sensitive to the following model inputs: infection-related mortality, life expectancy, and infection cost. The authors concluded that the absorbable antibacterial envelope was associated with a cost-effectiveness ratio below contemporary benchmarks in the WRAP-IT patient population, suggesting that the envelope provides value for the US healthcare system by reducing the incidence of CIED infection. In our next paper, Peter Loh and associates in this study aim to investigate the feasibility and safety of single pulse irreversible electroporation (IRE) pulmonary vein (PV) isolation in patients with atrial fibrillation (AF). Ten patients with symptomatic paroxysmal or persistent AF underwent single pulse IRE pulmonary vein isolation under general anesthesia. Three-dimensional reconstruction and electroanatomical voltage mapping of the left atrium and pulmonary veins were performed using a conventional circular mapping catheter. Pulmonary vein isolation was performed by delivering nonarcing, nonbarotraumatic 6 ms, 200 Joule direct current IRE applications via a custom nondeflectable 14-polar circular IRE ablation catheter with a variable hoop diameter (16–27 millimeters). A deflectable sheath was used to maneuver the ablation catheter. A minimum of 2 IRE applications with slightly different catheter positions were delivered per vein to achieve circular tissue contact, even if pulmonary vein potentials were abolished after the first application. Bidirectional pulmonary vein isolation was confirmed with the circular mapping catheter and a post ablation voltage map. After a 30-minute waiting period, adenosine testing was used to reveal dormant pulmonary vein conduction. All 40 pulmonary veins could be successfully isolated with a mean of 2.4 IRE applications per pulmonary vein. Mean delivery peak voltage and peak current were 2154 volts and 33.9 amperes. No pulmonary vein reconnections occurred during the waiting period and adenosine testing. No periprocedural complications were observed. The authors concluded that in 10 patients in this first in-human study, acute bidirectional electrical pulmonary vein isolation could be achieved safely using single pulse IRE ablation. In our next paper, Christian Sohns and associates studied the relationship between left ventricular ejection fraction (LVEF) New York Heart Association (NYHA) class on presentation and the end points of mortality and heart failure (HF) admissions in the CASTLE-AF study population. Furthermore, predictors for LVEF improvement were examined. The CASTLE-AF patients with coexisting heart failure and AF (n=363) were randomized in a multicenter prospective controlled fashion to ablation (n=179) versus pharmacological therapy (n=184). Left ventricular function in NYHA class were assessed at baseline after randomization and at each follow-up visit. In the ablation arm, a significantly higher number of patients experienced an improvement in their LVEF to greater than 35% at the end of the study (odds ratio, 2.17; PIn the next paper, Milena Leo and associates conducted a randomized study to compare risk of esophageal heating and acute procedure success of different LSI-guided ablation protocols combining higher or lower radiofrequency power or different target LSI values. Eighty consecutive patients were prospectively enrolled and randomized to one of 4 combinations of radiofrequency (RF) power and target LSI for ablation of the left atrial posterior wall (that is 20 watts LSI 4, 20 watts LSI 5, 40 watts LSI 4, and 40 watts LSI 5). The primary end point of the study was the occurrence and number of esophageal temperature alerts (ETAs) per patient during ablation. Acute indicators of procedure success were considered as secondary end points. Long-term follow-up data was also collected for all patients. Esophageal temperature alerts (ETAs) occurred in a similar proportion of patients in all groups. Significantly, shorter RF durations was required to achieve the target LSI in the 40 watt groups. Less than 50% of the RF lesions reached the target LSI of 5 when using 20 watts despite a longer RF duration. A lower rate of first-pass pulmonary vein isolation and a higher rate of acute pulmonary vein reconnection were recorded in the group 20 watts LSI 5. A lower AF recurrence rate was observed in the 40 watt groups compared with the 20 watts groups at 29 months follow-up. The authors concluded that when guided by LSI, posterior wall ablation with 40 watts is associated with a similar rate of ETAs and a lower AF recurrence rate at follow-up if compared with 20 watts. These data will provide a basis to plan future randomized trials. In the next paper, Shohreh Honarbakhsh and associates in this study aimed to determine whether STAR mapping using sequential recordings from conventional pulmonary vein mapping catheters could achieve similar results. Patients with persistent AF less than 2 years were included. Following pulmonary vein isolation (PVI), AF drivers were identified on sequential STAR maps created with PentaRay, IntellaMap Orion, or Advisor HD Grid catheters. Patients had a minimum of 10 multipolar recordings of 30 seconds each. These were processed in real-time and AF drivers were targeted with ablation. An ablation response was determined as AF termination or cycle length slowing greater than or equal to 30 milliseconds. Thirty patients were included, 62.4 years old, AF duration 14.1 months, of which 3 had AF terminated on pulmonary vein isolation, leaving 27 patients that underwent STAR-guided AF driver ablation. Eighty-three potential AF drivers were identified 3.1 per patient of which 70 were targeted with ablation (2.6 per patient). An ablation response was seen at 54 AFDs, 77.1% of AF drivers with 21 AF termination and 33 cycle length slowing and occurred in all 27 patients. No complications occurred. At 17.3 months, 22 out of 27 or 81.5% of patients undergoing STAR-guided ablation were free from atrial fibrillation, atrial tachycardia off antiarrhythmic drugs. The authors concluded that STAR-guided AF driver ablation through sequential mapping with a multipolar catheter effectively achieved an ablation response in all patients. AF termination in a majority of patients, with a high freedom from atrial fibrillation atrial tachycardia off antiarrhythmic drugs at long-term follow-up. In our next paper, Takashi Kaneshiro and associates sought to evaluate the characteristics of esophageal injuries in atrial fibrillation (AF) ablation using high power short duration setting. After exclusion of 5 patients with their esophagus at the right portion of left atrium and 21 patients with additional ablations such as box isolation and/or low voltage area in left atrium posterior wall, 271 consecutive patients, 62 years, 56 women, who underwent pulmonary vein isolation (PVI) by radiofrequency catheter ablation were analyzed. In the 101 patients, high power short duration setting at 45 to 50 watts with an Ablation Index module was used. In the remaining 170 patients, before introduction of the high power short duration setting, a conventional power setting of 20 to 30 watts with contact force monitoring was used, that is the conventional group. They performed esophagogastroduodenoscopy after pulmonary vein isolation in all patients and investigated the incidence and characteristics of esophageal thermal injury. Although the incidence of esophageal thermal injury was significantly higher in the high power short duration group compared with the conventional group (37% versus 22%, P=0.011), the prevalence of esophageal lesions did not differ between the groups (7% versus 8%). Multivariate logistic regression analysis revealed that the use of the high power short duration setting (odds ratio 6.09, PIn our next paper, Prasongchai Sattayaprasert, Sunil Vasireddi and associates hypothesize that in disease the inflammatory secretome of cardiac human mesenchymal stem cells remodels and can regulate arrhythmia substrates. Human cardiac mesenchymal stem cells were isolated from patients with or without heart failure from tissue attached to extracted device leads and from samples taken from explanted donor hearts. Failing human cardiac mesenchymal stem cells or nonfailing human cardiac mesenchymal stem cells were cocultured with normal human myoc

    37 min

  3. 01/12/2021

    Circulation: Arrhythmia and Electrophysiology September 2020 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, 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; PIn 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 (PIn 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 characterization, intracellular calcium imaging from isolated ventricular myocytes at baseline and after adrenergic stimulations were performed in wild-type and R67Q+/- mice. R67Q+/- mice (n=17) showed normal cardiac function structure baseline electrical activity compared to wild-type (n=10). Following epinephrine and caffeine, only the R67Q+/- mice had bidirectional ventricular tachycardia, frequent ventricular ectopy and/or bigeminy and optical mapping demonstrated high prevalence of spontaneous and sustained ventricular arrhythmia. Both R67Q+/- (n=8) and wild-type myocytes (n=9) demonstrated typical n-shaped IK1 IV relationship. However, following isoproterenol, max outward IK1 increased by about 20% in wild-type, but decreased by 24% in R67Q+/- (PIn our next paper, Michael Liu and associates use computational

    35 min

  4. 12/23/2020

    Circulation: Arrhythmia and Electrophysiology July 2020 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. Albert Feeny and Associates used unsupervised machine learning of electrocardiogram [ECG] waveforms to identify cardiac resynchronization therapy [CRT] subgroups to differentiate outcomes beyond QRS duration and left bundle branch block. They retrospectively analyzed 946 CRT patients with conduction delay. Principal component analysis [PCA] dimensionality reduction obtained a 2-dimensional representation of pre-CRT 12-lead QRS waveforms. K-means clustering of the 2-dimensional PCA representation of 12-lead QRS waveforms identified two patient subgroups [QRS PCA groups]. Vectorcardiographic QRS area was also calculated. They examined two primary outcomes: (1) composite endpoint of death, left ventricular assist device, or heart transplant, and (2) degree of echocardiographic left ventricular ejection fraction [LVEF] change after CRT. Compared to QRS PCA group 2 (n = 425), Group 1 (n=521) had a lower risk for achieving the composite endpoint (hazard ratio of 0.44, P In our next paper, Julie Shade, Rheeda Ali and Associates combined machine learning [ML] and personalized computational modeling to predict, prior to pulmonary vein isolation [PVI], which patients are most likely to experience atrial fibrillation [AF] recurrence after PVI. The single center retrospective proof of concept study included 32 patients with documented paroxysmal AF who underwent PVI and had pre-procedural late gadolinium enhanced magnetic resonance imaging [LGE MRI]. For each patient, a personalized computational model of the left atrium simulated AF induction via rapid pacing features were derived from pre-PVI LG MRI images and from results of simulations [SIM] AF. The most predictive features used to input to a quadratic discrimination analysis ML classifier, which was trained, optimized, and evaluated with a 10-fold nested cross validation to predict the probability of AF recurrence post PVI. In the cohort, the ML classifier predicted probability of AF recurrence with an average validation, sensitivity, and specificity of 82% and 89% respectively, and a validation AUC of 0.82. Dissecting the relative contributions of simulations SIM AF and raw images to the predictive capability of the ML classifier, they found that only when features from simulation SIM AF were used to train the ML classifier, its performance retained similar (validation AUC equals 0.81). However, when only features classified from raw images were used for training, the validation AUC significantly decreased (0.47). In our next paper, Sarah Vermij and Associates examined sodium channel NaV 1.5 localization and function mutations in the gene and coding the sodium channel NaV 1.5 caused various cardiac arrhythmias. The authors use novel single-molecule localization [S-M-L-M] and computational modeling to define nanoscale features of NaV 1.5 localization and distribution at the lateral membrane [L-M], the LM groove, and T-tubules in cardiomyocytes from wild-type (N=3), dystrophin-deficient (mdx; N=3) mice, and mice expressing C-terminally truncated NaV 1.5 (ΔSIV; N=3). The authors assessed T-tubules sodium current by recording whole-cell sodium currents in control (N=5) in detubulated (N=5) wild-type cardiomyocytes. The authors found that NaV 1.5 organizes as distinct clusters in the groove and T-tubules which density, distribution, and organization partially depend on SIV and dystrophin. They found that overall reduction in NaV 1.5 expression expressed in mdx and ΔSIV cells result in a non-uniform distribution with NaV 1.5 being specifically reduced at the groove ΔSIV and increased in T-tubules of mdx cardiomyocytes. A T-tubules sodium current could, however, not be demonstrated. The authors concluded that NaV 1.5 mutations may site-specifically affect NaV 1.5 localization and distribution at the lateral membrane and T-tubules, depending on site-specific interacting proteins. In our next paper, Sharan Sharma, Mohit Turagam, and associates studied strategies to improve patient comfort related to pericardial access. They conducted a multi-centered retrospective study, including 104 patients who underwent epicardial ventricular tachycardia [VT] ablation and Lariat left atrial appendage occlusion. They compared 53 patients who received post-procedural intrapericardial liposomal bupivacaine (LB)+oral colchicine (LB group) and 51 patients who received colchicine alone (non-LB group). Lyposomal bupivacaine was associated with significant lowering of median pain scale at 6 hours (1.0 versus 8.0, PIn our next paper, Sergio Callegari, Emilio Macchi, and Associates characterize the fibrosis (amount, architecture, cellular components, and ultrastructure) in left atrial biopsies from 121 patients with persistent/long-lasting atrial fibrillation [AF] (group 1; 59 males; 60 years of age; 91 mitral disease-related AF, 30 nonmitral disease-related AF) and 39 patients in sinus rhythm with mitral valve regurgitation (group 2; 32 males; 59 years of age). 10 autopsy hearts served as controls. Qualitatively, the fibrosis exhibited the same characteristics in all cases and displayed particular architectural scenarios (which the authors arbitrarily divided into four stages) ranging from isolated foci to confluent sclerotic areas. The percentage of fibrosis was larger and in a more advanced stage in group 1 versus group 2 and within group 1, in patients with rheumatic disease versus non-rheumatic cases. In AF patients with mitral disease and no rheumatic disease, the percentage of fibrosis and the fibrosis stages correlated with both left atrial volume index and AF duration. The fibrotic areas mainly consisted of type I collagen with only a minor cellular component (especially fibroblasts/myofibroblasts; average value range 69–150 cells/mm2, depending on the areas in AF biopsies). A few fibrocytes, circulating and bone marrow-derived mesenchymal cells, were also detectable. The fibrosis-entrapped cardiomyocytes showed sarcolemmal damage and connexin 43 redistribution/internalization. In our next paper, Shijie Zhou and Associates tested an automated localization system to identify the site of origin of left ventricular [LV] activation in real time using 12-lead ECG. The automated site of origin, solo system, consists of three steps: (1) localization of ventricular segment based on population templates, (2) population-based localization within a segment, and, (3) patient-specific site localization. Localization error was assessed by the distance between the known reference site and the estimated site. In 19 patients undergoing 21 catheter ablation procedures of scar related VT, solo accuracy was estimated using 552 LV left endocardial pacing sites pooled together and 25 VT-exit sites identified by contact mapping. For the 25 VT-exit sites, localization error of the population-based localization steps was within 10 mm. Patient-specific site localization achieved accuracy of within 3.5 mm after including up to 11 pacing (training) sites. Using 3 remotes (67.8 mm from the reference VT-exit site), and then 5 close pacing sites, resulted in localization error of 7.2 mm for the 25 identified VT-exit sites. In 2 emulated clinical procedure with 2 induced VT's, the solo system achieved accuracy within 4 mm. In our next paper, Ryan Koene and associates examined outcomes of use of dofetilide in atrial fibrillation [AF] patients with left ventricular ejection fraction [LVEF]≤35% without prior implantable cardioverter defibrillator [ICD] cardiac resynchronization therapy [CRT], or AF ablation. An analysis of 168 consecutive patients from 2007 to 2016 was performed. Incidences of adverse events, drug discontinuation, ICD, or CRT implementation, LVEF improvement (>35%) and recovery (50% or greater), AF recurrence, and AF ablation were determined. Multi-variate regression analysis to identify predictors of LVEF improvement/recovery was performed. The mean age was 64 years. Dofetilide was discontinued prior to hospital discharge in 46 (27%) because of QT prolongation (14%), torsades de pointe or polymorphic ventricular tachycardia/ventricular fibrillation (6% [sustained 3%, nonsustained 3%]), in effectiveness (5%), and other causes (3%). At one year 43% remained on dofetilide. Freedom from AF was 42% at 1 year and 40% underwent future AF ablation. LVEF recovered to 50% or greater in 45% and an improved to greater than 35% in 73%. Predictors of LVEF improvement included presence of AF during echocardiogram (odds ratio 4.22, P=0.002), coronary artery disease (odds ratio 0.35, P=0.01), left atrial diameter (odds ratio, 0.52 per 1 cm increase, P=0.01), and LVEF (odds ratio, per 1% increase, 1.09, P=0.006). The C statistic was 0.78. Our next paper is a research letter by Giuseppe Ciliberti, Gherardo Finocchiaro, and Associates. Myocardial infarction with nonobstructive coronary arteries, MINOCA, accounts for one to 10% of all causes of acute myocardial infarction [MI]. The authors examine 37, that is 0.7% of the entire study population, sudden cardiac death cases of MINOCA. The majority of decedents were male (N=23, 62%), mean age at death was 34 years, age range 13 to 96 years. Death occurred at rest or during daily activities in 36, that is 97% of individuals. Coronary thrombosis was found at 9 out of 13 at a 69% with nonobstructive atherosclerosis. Drug use was reported in 10 or 27%. Our next paper is a special report entitled HRS/EHRA/APHRS/LAHRS/ACC/AHA worldwide practice update for tele-health and arrhythmia monitoring during and after a pandemic. This document discusses how digital health may facilitate electrophysiology practice in patients with arrhythmia. Electrophysiology is well placed for virtual consultation. Digital tools such as direct to consumer mobile ECG and wireless blood pressu

    20 min

  5. 12/22/2020

    Circulation: Arrhythmia and Electrophysiology August 2020 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, Demilade Adedinsewo and associates assess the accuracy of an artificial intelligence-enabled electrocardiogram [AI-ECG] to identify patients presenting with dyspnea who have left ventricular LV systolic function (defined as LV ejection fraction ≤35%) in the emergency department [ED]. Patients were included if they had at least one standard 12-lead electrocardiogram [ECG] acquired on the date of the ED visit and an echocardiogram performed within 30 days of presentation. Patients with prior LV systolic dysfunction were excluded. A total of 1,606 patients were included. Meantime from ECG echocardiogram was one day. The AI-ECG algorithm identified LV systolic dysfunction with an area under the curve [AUC] of 0.89 and accuracy of 85.9%. Sensitivity was 74%, specificity 87%, negative predictive value 97%, and positive predictive value 40%. To identify an ejection fraction less than 50%, the AUC was 0.85, sensitivity 86%, sensitivity 63%, and specificity 91%. NT-proBNP alone with a cutoff greater than 800 identified LV systolic function with an AUC of 0.80 by comparison. In our next paper, Mahmood Alhusseini and associates hypothesize that convolutional neural networks [CNN] may enable objective analysis of intracardiac activation in atrial fibrillation [AF]. They perform panoramic recording of bi-atrial electrical signals in AF and use the Hilbert-transform to produce 175,000 image grids in 35 patients labeled for a rotational activation by experts who showed consistency, but with variability (kappa [κ]=0.79). In each patient, ablation terminated atrial fibrillation. A CNN was developed and trained on 100,000 AF image grids validated on 25,000 grids, and then tested on a separate 50,000 grids. They found in a separate test cohort of 50,000 grids, CNN reproducibly classified AF image grids into those with or without rotational sites with 95.0% accuracy. This accuracy exceeded that of support vector machines, traditional linear discriminant, and k-nearest neighbor statistical analyses. To probe the CNN, they applied gradient weighted class activation mapping, which revealed that the decision logic closely mimicked rules used by experts (C statistic 0.96). The authors concluded that convolutional neural networks improve the classification of intercardiac AF maps compared to other analyses and agreed with expert evaluation. In our next paper, Kenji Okubo and associates examined whether late potential LP, abolition and ventricular tachycardia [VT] non-inclusive ability predicted long-term outcomes in patients with non-ischemic cardiomyopathy [NICM] undergoing VT ablation. The total 403 patients with NICM (523 procedures) who underwent VT ablation from 2010 to 2016 were included. The underlying structural disease consists of dilated cardiomyopathy (DCM, 49%), arrhythmogenic right ventricular cardiomyopathy (ARVD 17%), postmyocarditis (14%), valvular heart disease (8%), congenital heart disease (2%), hypertrophic cardiomyopathy (2%), and others (5%). Epicardial access was performed in 57% of patients. At baseline, the LPs were present in 60% of patients, and a VT was either inducible or sustained/incessant in 85% of the cases. At the end of the procedure LP abolition was achieved in 79% of cases in VT noninducability in 80%. After a multivariate analysis, the combination of LP abolition and VT noninducibility was independently associated with free survival from VT (hazard ratio, 0.45, p = 0.0002) and cardiac death (hazard ratio 0.38, P = 0.005). The benefit of LP abolition of preventing the VT recurrence in ARVD and postmyocarditis appeared superior to that observed for DCM. In our next paper, Domenico Corradi, Jeffrey Saffitz and associates hypothesize that structural molecular changes in atrial myocardium that correlate with myocardial injury and precede and predict postoperative atrial fibrillation [POAF] may identify new molecular pathways and targets for prevention of this common morbid complication. Right atrial appendage [RAA] samples were prospectively collected during cardiac surgery from 239 patients enrolled in the OPERA trial. 35.2% of patients experienced POAF compared to the non-POAF group. They were significantly older and more likely to have chronic obstructive pulmonary disease or heart failure. They had a higher Euro score and more often underwent valve surgery. No differences in atrial size were observed between POAF and non-POAF patients. The extent of atrial interstitial fibrosis, cardiomyocyte myocytolysis, cardiomyocyte diameter, glycogen storage, or connection 43 distribution at the time of surgery, was not significantly associated with the incidents of POAF. None of these histopathological abnormalities were correlated with level of NT pro-BNP, hs-cTnT, CRP, or oxidative stress biomarkers. The authors concluded that in sinus rhythm patients undergoing cardiac surgery, histopathological changes in RAA do not predict POAF. They did not also correlate with biomarkers of cardiac function, inflammation, and oxidative stress. In our next paper, Mark McCauley, Liang Hong, Arvind Sridhar, and associates hypothesize that obesity decreases sodium channel NAF 1.5 expression via enhanced oxidative stress, thus reducing the sodium current and enhancing susceptibility to atrial fibrillation [AF]. They studied a diet induced obese [DIO] mouse model. Pacing induced AF in 100% of DIO mice versus 25% in controls (PIn our next, paper Hirosuke Yamaji and associates conducted a randomized control trial to examine the impact of electrophysiological evaluation of the left atrium on atrial fibrillation [AF] outcome. They examined consecutive persistent and patients with, in 33, and without, 111 patients left atrial [LA] low voltage areas [LA-LVA]. Patients without LA-LVA were randomly assigned to EP test-guided (n=57) and control (n=54). In the EP test-guided group, an adjunctive posterior wall isolation [PWI] was performed in those with positive results (PWI subgroup; n=24) but not those with negative results (n=33). The criteria for positive EP tests were an effective refractory period ≤180 ms, ERP > 20 ms shorter than the other sites, and/or induction of AF/atrial tachycardia during measurements. LVA ablation was performed in the LA-LVA patients during the follow-up period of a mean of 62 weeks, the EP test-guided group had a significantly lower recurrence rate (19%,11/57 versus 41%, 22/54, P=0.012) and a higher Kaplan-Meier AF/AT-free survival curve compared with controls (P=0.01). No significant differences in the recurrence, and AF/AT-free survival curves between PWI (positive EP test) and non-PWI (negative EP test) subgroups were observed. Therefore, PWI for positive EP tests reduced the AF/AT recurrence in the EP test-guided group. A stepwise Cox proportional hazard analysis identified EP test-guided ablation as a factor, reducing recurrence rates. The recurrence rates in LA-LVA ablation group and EP test-guided group were similar. In our next study, Jinxuan Lin and associates assess whether simultaneous pacing of the left and right bundle branch areas may achieve more synchronous ventricular activation than just bundle pacing alone. In symptomatic bradycardia patients, the distal electrode of the bipolar pacing lead was placed at the left bundle branch area via a transventricular-septal approach. This was used to pace the left bundle branch area, while the ring electrode was used to pace the right bundle branch area. Bilateral bundle branch area pacing [BBBP] was achieved by stimulating the cathode and anode in various configurations. BBBP was successfully performed in 22 out of 36 patients. Compared with LBBP, BBBP resulted in greater shortening of QRS duration (109.3 vs 118.4 ms, P In our next paper, Ramanathan Parameswaran, Jonathan Kalman, Geoffrey Lee and associates recorded 2-minute long segments of simultaneous inter-operative mapping of endo- and epicardial lateral right atrial [RA] wall in patients with persistent atrial fibrillation [AF] using 2 high-density grid catheters (16 electrodes, 3 mm spacing). Filtered unipolar and bipolar electrograms [EGMS] of continuous 2-minute AF recordings and electrodes locations were exported for phase analysis. They defined endocardial-epicardial dissociation [EED] as phase differences of ≥20 ms between paired endo- and epi electrodes. Wavefronts [WF] were classified as single rotations, that is single wavefront, focal waves, or disorganized activity as per standard criteria. Endo-Epi wave fronts were simultaneously compared on dynamic phase maps. Complex fractionated electrograms were defined as bipolar electrograms with directional changes occupying at least 70% of the sample area. 14 patients with persistent AF underwent cardiac surgery are included. EED was seen in 50.3% of phase maps with significant temporal heterogeneity. Disorganized activity (endo 41.3%, epi 46.8%, P = 0.0194) and single wave (endo 31.3 versus epi 28.1, P = 0.129) were the dominant patterns. Transient rotations (endo 22%, epi 19.2%, P = 0.169, mean duration 590 ms) and non-sustained focal waves (endo 1.2% and epi 1.6%, P = 0.669) were also observed. Apparent transmural migration of rotational activations (n=6) from the epi- to the endocardium was seen in 2 patients. EGM fractionation was significantly higher in the epicardium than endocardium (61.2% versus 51.6%, P In our next paper, Andrew Beaser and associates hypothesize that intravascular ultrasound [IVUS] could accurately visualize and quantify intravascular lead adherence and degree of intravascular lead adherence correlates with transvenous lead extraction difficulty. Serial imaging of leads occurred prior to transvenous lead extraction using IVUS. Intravascular lead adherence areas were classified

    36 min

  6. 12/22/2020

    Circulation: Arrhythmia and Electrophysiology June 2020 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, Vivek Reddy and associates studied a novel, 7.5, French lattice tip catheter with the compressible 9 mm nitinol tip that is able to deliver either focal radio frequency ablation [RFA] or pulsed field ablation [PFA], 2 to 5 second lesions. In a 3 center, single-arm, first in human trial, the catheter was used with a custom mapping system to treat paroxysmal or persistent atrial fibrillation. Toggling between energy sources, point by point, pulmonary vein [PV] encirclement was performed using biphasic pulsed field ablation, posteriorly, and either temperature controlled irrigated RFA or pulse field ablation, anteriorly (RF/PF or PF/PF) respectively. Linear lesions were created with either PFA or RFA. The 76 patient cohort included 55 paroxysmal and 21 persistent atrial fibrillation [AF] patients undergoing either RF/PF [pulse field ablation] 40 patients or PF/PF ablation in 36 patients, pulmonary vein isolation therapy duration was 22.6 minutes per patient with a mean of 50.1 RF/PF ablation lesions per patient. Linear lesions included 14 mitral, 34 left atrial roof and 44 cavo-tricuspid isthmus lines with therapy duration times of 5.1, 1.8 and 2.4 min/patient respectively. All lesion sets were acutely successful using 4.7 minutes of fluoroscopy. There were no device-related complications, including no strokes. Post-procedure esophagogastroduodenoscopy revealed minor mucosal thermal injury in two of the 36 RF/PF and zero of the 24 PF/PF patients. Post-procedure brain MRI revealed DWI positive flair, negative and DWI positive flare positive asymptomatic lesions in 5 and 3 of the 51 patients respectively.   In our next paper, Moussa Saleh and associates examined whether chloroquine, hydroxychloroquine plus or minus azithromycin lead to a prolongation of the QT interval, possibly increasing the risk of torsades de pointes and sudden death in a hospitalized population of patients with COVID-19. 201 patients were treated for COVID-19 with chloroquine/hydroxychloroquine. 10 patients or 5% received chloroquine, and 191 or 95% received hydroxychloroquine and 119 or 59% also received azithromycin. The primary outcome of Torsades de pointes was not observed in the entire population. Baseline QTC interval did not differ between patients treated with chloroquine or hydroxychloroquine monotherapy versus those treated with combination group chloroquine/hydroxychloroquine and azithromycin (440 ms versus 439.9 ms). The maximum QT during treatment was significantly longer in the combination versus the monotherapy group, 470 ms versus 453 ms (P = 0.004). Seven patients (3.5%) required discontinuation of these medications due to QTC prolongation. No arrhythmic deaths were reported.   In our next paper, Mikko Tulppo and associates examine whether the association between leisure time physical activity and the risk of sudden death and non-sudden cardiac death in coronary artery disease patients. 1,946 patients with angiographically verified coronary artery disease were classified into four groups: inactive, irregularly active, active exercise regularly two to three times per week, and highly active, exercise four times or more weekly. During follow-up, median 6.3 years, 52 sudden cardiac death and 49 non-sudden cardiac deaths occurred. Inactive patients had increased risk for sudden cardiac death compared to active patients, hazard ratio 2.45. Leisure time was not associated with sudden cardiac death in patients with Canadian cardiovascular class one, 18 events in 1,107 patients. Among patients with Canadian cardiovascular society, class two or higher, 34 events in 839 patients. An increased risk for sudden cardiac death encountered in highly active patients, hazard ratio 7.46 (P   In our next paper, Jacob Koruth and associates examined the preclinical feasibility and safety of a 9mm lattice tip catheter with focal biphasic pulse field [PF] based thoracic vein isolation and linear ablation combined focal biphasic pulse field and radio-frequency [RF] focal ablation and vocal biphasic pulse field delivered directly on top of the esophagus. They treated two cohorts of six swine with pulse fields at low dose and high dose followed for four weeks and two weeks, respectively to isolate 25 thoracic veins and to create five right atrial low dose PF, six mitral high dose PF, and six roof lines with combined RF and high dose PF. Baseline and follow-up voltage mapping, venus potentials, ostial diameters and phrenic nerve viability were assessed. High dose PF in RF lesions were delivered in 4 and 1 swine from the inferior vena cava onto a forcefully deviate esophagus. 100% of thoracic veins, 25 out of 25, were successfully isolated with 12.4 applications per vein with a mean pulse field times of less than 90 seconds per vein. Durable isolation improved from 61.5% in the low dose pulse field to 100% with a high dose pulse field (P = 0.04). And all linear lesions were successfully completed without incurring venous stenosis or phrenic injury. High dose pulse field sections had higher trans mortality rates than low dose pulse field (98.3% versus 88.1%, P = 0.03). Despite greater thickness, 2.5 versus 1.3 mm, pulse field lesions demonstrated homogeneous fibrosis without epicardial fat, nerve or vessel involvement. In comparison, combined RF plus high dose PF sections revealed similar transmurality, but expectedly more necrosis, inflammation and epicardial fat, nerve and vessel involvement. Significant ablation related esophageal and necrosis inflammation and fibrosis were seen in all RF sections as compared to no PF sections.   In our next paper, Hagai Yavin and associates investigated the effects of a novel, lattice tip catheter designed for focal radiofrequency ablation [RFA] or pulse field ablation in 25 swine. In 14 animals, they examined in step one (n = 14) the feasibility to create atrial line of block and described as acute effects on the phrenic nerve and esophagus. In step two (n = 7), they examined the subacute effects of pulse field ablation on block durability, phrenic nerve, and esophagus 2 or more weeks. In 4 animals in step three, they compare the effects of pulse field ablation and RFA on the esophagus using a mechanical deviation model, approximating the esophagus through the right atrium in 4 and direct ablation honest lumen in 4. The effects of endocardial PFA and RFA on the phrenic nerve were also compared (n = 10). Histological analysis were performed. Pulse field ablation produced acute block in 100% of lines achieved with 2.1 applications per centimeter line. Histological analysis following a mean of 35 days showed 100% transmurality (thickness range 0.4 to 3.4 mm) with a lesion width of 19.4 mm. Pulse field ablation selectively affected cardiomyocytes, but spared blood vessels and nervous tissue. Pulse field ablation applied from the posterior atrium to the approximated esophagus produced transmural lesions without esophageal injury. Pulse field ablation applied within the esophageal lumen produced mild edema compared to radiofrequency ablation (13 applications) which produced epithelial ulcerations. Pulse field ablation resulted in no or transient stunning of the phrenic nerve, less than 5 minutes without histological changes while radiofrequency ablation produced paralysis.   In our next paper, Elad Anter and associates investigated the optimal methods to identify arrhythmogenic substrate of scar related VT. They examine how often sites of activation slowing during sinus rhythm co localize with ventricular tachycardia VT circuit. In a multicenter study in patients with infarct-related VT, the left ventricle was mapped during activation from three directions, sinus rhythm, or atrial pacing, right ventricular and left ventricular LV pacing at 600 ms. Ablation was applied selectively to the cumulative area of slow activation defined as a sum of all regions with activation time of 40 ms or greater per 10 mm. Hemodynamically tolerated ventricular tachycardias or VT were mapped with activation or entrainment. The primary outcome was a composite of appropriate ICD therapies and cardiovascular death. In 85 patients, the left ventricle was mapped during activation from 2.4 directions. The direction of LV activation influenced the location and magnitude of activation slowing. The spacial overlap of activation slowing between sinus rhythm and right ventricular RV pacing was 84.2%, between sinus rhythm and LV pacing was 61.4%, and between right ventricular and left ventricular pacing, 71.3% (P   In our next paper, Georg Gussak and associates identified a novel form of abnormal calcium wave activity in normal and failing dog atrial myocytes, which occurs during the action potential and is absent during diastole. The goal of this study was to determine if triggered calcium waves affect cellular electrophysiological properties. The authors use simultaneous recordings of intracellular calcium, and action potentials for the measurement of maximum diastolic potential and action potential duration during triggered calcium waves in isolated dog atrial myocytes. Computer simulations then explored electrophysiological behavior arising from triggered calcium waves at the tissue scale. At 3.3 to five Hertz, triggered calcium waves occurred during the action potential and outlasted several action potential cycles. Maximum diastolic potential was reduced and actual potential duration was significant prolonged during trigger calcium waves. All electrophysiological responses that triggered calcium waves were abolished by using SCA 0400 and ORM 10103, indicating that sodium calcium exchange current caused depolarization. The time constant recovery from inactivation of calcium current was 40 to 70 ms in atrial

    19 min

  7. 12/16/2020

    Circulation: Arrhythmia and Electrophysiology May 2020 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, Bruce Wilkoff and associates examine the impact of cardiac implantable electronic device [CIED] infections on mortality, quality of life, healthcare utilization, and cost in the U.S. Healthcare system. They found that the majority CIED infection was associated with increased all-cause mortality, 12-month risk-adjusted hazard ratio 3.41, P   The quality of life was reduced, P = 0.004, and did not normalize for six months. Disruptions in CIED therapy were observed in 36% of infections for a median duration of 184 days. The authors reported that the mean hospital costs were $55,547.   In our next paper, Songwen Chen, Xiaofeng Lu and associates examine the ability to eliminate premature ventricular complexes [PVCs] originating from the proximal left anterior fascicle, safely from the right coronary sinus. The authors mapped the the right coronary sinus and left ventricle in 20 patients with left anterior fascicle PVCs. They found that the earliest activation site with Purkinje potential during both PVC and sinus rhythm was localized at proximal left anterior fascicle in eight patients, the proximal group, or non-proximal left anterior fascicle in 12 groups, the non-proximal group. The Purkinje potentials proceeded PVC-QRS at the earliest activation site in proximal group 32.6 milliseconds was significantly earlier than that in non-proximal group, 28.3 milliseconds P = 0.025. Similar difference in the Purkinje potentials proceeding sinus QRS at the earliest activation site was also observed between proximal and non-proximal group, 35.1 milliseconds versus 25.2 milliseconds, P   In proximal group, the distance between the earliest activation site to the left His-bundle into the right coronary sinus were shorter than that of the non-proximal group 12.3 millimeters versus 19.7, P = 0.002, and 3.9 millimeters versus 15.7 millimeters, P   Electrocardiographic analysis showed that when compared to non-proximal group, the PVCs proximal group had a narrower QRS duration, smaller S wave in leads one, V five,and V six; lower R waves in leads one, aVL, aVR, V one, V two, and V four and smaller q wave in leads three and aVF. The QRS duration difference [PVC-QRS and sinus rhythm QRS]   In our next paper, Benjamin Steinberg and associates examined the factors that are associated with large improvements in health-related quality of life in patients with atrial fibrillation. The authors assessed factors associated with a one-year increase in quality of life, measured by AFEQT of one standard deviation that is greater and equal to 18 points, three times clinically important difference among patients in the ORBIT-AF one registry. They found that 28% of patients had such a health-related quality improvement compared with patients not showing large health-related quality of life improvement. They were similar age, (median 73 versus 74 years of age), equally likely to be female, (44% versus 48%), but more likely to have newly diagnosed atrial fibrillation [AF] at baseline (18% versus 8%, P = 0.0004) prior antiarrhythmic drug use (52% versus 40%, P = 0.005), baseline antiarrhythmic drug use (34.8% versus 26.8%, P = 0.045), and more likely to undergo AF related procedures during follow-up (AF ablation 6.6% versus 2.0%, cardioversion 12.2% versus 5.9%). In multivariate analysis, a history of alcohol abuse has a ratio 2.4 and increased baseline diastolic blood pressure has a ratio 1.23 per 10 point increase and greater than 65 millimeters of mercury were associated with large improvements in health-related quality of life at one year. Whereas patients with prior stroke, chronic obstructive pulmonary disease and peripheral artery disease were less likely to improve.   In our next paper, Eiichi Watanabe and associates studied safety and resource consumption of exclusive remote follow-up in pacemaker patients for two years. Consecutive pacemaker patients committed to remote pacemaker management were randomized to either remote follow-up or conventional in-office follow-up at twice yearly intervals.   Remote follow-up patients were only seen if indicated by remote monitoring, all returned to hospital after two years. In 1,274 randomized patients (50.4% female, age 77 years), 558 remote follow-up or 550 conventional in office follow-up patients reached either the primary end point or 24 months follow-up. The primary end point, a composite of death, stroke, or cardiovascular events requiring surgery occurred in 10.9% and 11.8% respectively in the two groups (P = 0.0012) for non-inferiority. The median number of in-office follow-ups was 0.5 in the remote follow-up group and 2.01 in the conventional in-office follow-up per patient year (P   In our next paper, Sarah Strand and associates use fetal magnetocardiography from the University of Wisconsin biomagnetism laboratory to study 39 fetuses with pathogenic variants in long QT syndrome, LQTS genes. 27 carried the family variant, 11 had de novo variants, and one was indeterminant. De novo variants, especially de novo SCN5A variants were strongly associated with a severe rhythm phenotype and perinatal death. Nine or 82% showed signature LQTS rhythms, six showed torsade de pointes, five were still born, and 9% died in infancy. Those that died exhibited novel fetus rythms, including AV block with 3:1 conduction ratio, QRS alternans in 2:1 AV block, long cycle length, torsade de pointes, and slow monomorphic ventricular tachycardia. Premature ventricular contractions were also strongly associated with torsade de pointes and perinatal death. Fetuses with familiar variants showed a lower incidence of signature LQTS rhythm, six out of 27 or 22%, including torsade de pointes, and 3 out of 27 or 11% all were live born. The authors concluded that the malignancy of de novo LQTS variants was remarkably high and demonstrate that these mutations are a significant cause of stillbirth.   In our next paper, Corina Schram-Serban and associates compare the severity of extensiveness of conduction disorders between obese patients and non-obese patients measured at high resolution scale. They studied 212 patients undergoing cardiac surgery (male:161, mean 63 years of age), who underwent epicardial mapping of the right atrium, Bachmann's bundle, and left atrium during sinus rhythm. Conduction delay [CD] was defined as interelectrode conduction time seven to 11 milliseconds and conduction block [CB] as conduction time ≥ 12 milliseconds. In obese patients, the overall incidence of conduction delay was 3.1% versus 2.6% (P = 0.002), conduction block 1.8% versus 1.2%, and continuous CDCB 2.6% versus 1.9% higher in the obese patients, conduction delay (P = 0.012) and continuous CDCB lines are longer. There were more conduction disorders at Bachman's bundle, and this area has a higher incidence of conduction delay 4.4% versus 3.3% (P = 0.002), conduction block 3.1% versus 1.6% (P   In our next paper, Ricardo Cardona-Guarache and associates describe five patients with concealed, left-sided nodoventricular in four patients and nodofascicular in one patient accessory pathways. They proved the participation of accessory pathway in tachycardia by delivering His-synchronous premature ventricular complexes that either delayed the subsequent atrial electrogram or terminated the tachycardia, and by observing an increase in ventricular atrial interval coincident with left bundle branch block in two patients. The accessory pathways were not atrioventricular pathways because the septal ventricular atrial interval during tachycardia was less than 70 milliseconds in 3, 1 had spontaneous AV dissociation, and in 1 the atria were dissociated from the circuit with atrial overdrive pacing.   Entrainment from the right ventricle showed ventricular fusion in 4 out of 5 cases. A left-sided origin of accessory pathways was suspected after failed ablation of the right inferior extension of the AV node in 3 cases and by observing VA increase in left bundle branch block in 2 cases. The nodofascicular in 3 of the 4 nodoventricular accessory pathways were successfully ablated from within the proximal coronary sinus guided by recorded potentials at the roof of the coronary sinus, and nodoventricular accessory pathway was ablated via a transseptal approach near the coronary sinus os.   In our next paper, Pierre Qian and associates examined whether an open irrigated microwave catheter ablation can achieve deep myocardial lesions endocardially and epicardially through fat while acutely sparing nearby coronary arteries. Epicardial ablations via subxiphoid access in pigs were performed at 90 to 100 Watts at four minutes at sites near coronary arteries and produced mean lesion depth of 10 millimeters, width 18 millimeters, and length 29 millimeters through median epicardial fat thickness of 1.2 millimeters. Endocardial ablations at 180 Watts achieved depths of 10.7 millimeters, width of 16.6 millimeters, and length of 20 millimeters. Acute coronary occlusion or spasm was not observed at median separation distance of 2.7 millimeters.   In our next paper, Jad Ballout and associates examined 21 consecutive patients with cardiogenic shock and refractory ventricular arrhythmias undergoing bailout ablation due to inability to wean off of mechanical support. Mean age was 61 years, 86% were males, median left ventricular injection fraction 20%, 81% ischemic cardiomyopathy. The type of mechanical support in place prior to the procedure was intra-aortic balloon pump in 14 patients, Impella in 2, ECMO in 2, ECMO and intra-aortic balloon pump in 2, and ECMO and Impella in 1. In the cardio voltage maps with myocardial scar in 90% (19 patients), the clinical ventricular tachycardias VTs were inducible in 13% (62 patien

    18 min

  8. 12/16/2020

    Circulation: Arrhythmia and Electrophysiology April 2020 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, David Okada and associates assess the ability of a novel machine learning approach for quantifying 3D spatial complexity of gray scale patterns on late gadolinium-enhanced cardiac magnetic resonance images to predict ventricular arrhythmias in patients with ischemic cardiomyopathy.   They examined 122 consecutive ischemic cardiomyopathy patients with left ventricular ejection fraction of 35%, without prior history of reentrant ventricular arrhythmias. These patients underwent late gadolinium-enhanced cardiac magnetic resonance imaging. From raw gray scale data, the authors generated graphs encoding the 3D geometry of the left ventricle. They then assess the global regularity of signal intensity patterns using Fourier-like analysis and generated a substrate spatial complexity profile for each patient. A machine learning statistical algorithm was employed to discern which substrate spatial complexity profiles correlated with ventricular arrhythmic events. That is appropriate ICD firings and arrhythmic sudden cardiac death.   At five years of follow-up from the statistical machine learning results, a complexity score ranging from zero to one was calculated for each patient that was tested using multivariate Cox regression models. At five years of follow-up, 40 patients had ventricular arrhythmia events. The machine learning algorithm classified with overall 81% accuracy and correctly classified 86% of those without ventricular arrhythmia. Overall negative predictive value was 91%. Average complexity score was significantly higher in patients with ventricular arrhythmia events versus those without P  In our next paper, Henry Chubb and associates examine the outcomes of cardiac resynchronization therapy studies in pediatric and or congenital heart disease patients using a propensity score match analysis. They examined 63 matched CRT control pairs. Heart transplant or death occurred in 12 subjects or 19% or 37 controls or 59% with a median follow-up of 2.7 years. Cardiac resynchronization therapy was associated with markedly reduced risk of heart transplant or death. Hazard ratio is 0.24 P  In our next paper Pachon-M and associates examined whether AF nest ablation eliminates the atropine response and decreases RR variability suggesting that they're related to vagal innervation. The authors perform prospective control longitudinal randomized study enrolling 62 patients in two groups, AF nest group that is 32 patients with functional or reflex Bradyarrhythmias or vagal AF treated with AF Nest ablation and a control group, 30 patients with anomalous bundles, ventricular prematures, atrial flutter, AV nodal reentry and atrial tachycardias who were treated with a conventional ablation approach.   In the AF nest group, ablation was delivered at the AF nest detected by fragmentation or fractionation of the endocardial electrograms and by 3D anatomical location of the ganglionated plexus. Vagal response was evaluated before, during and post ablation by five seconds non-contact vagal stimulation at the jugular foramen through the internal jugular veins, analyzing 15 seconds mean heart rate, longest RR pauses and AV block. A pre-ablation non-contact vagal stimulation due sinus pauses, asystole, and transient AV block in both groups showing a strong vagal response.   Post-ablation non-contact vagal stimulation in the AF nest showed complete abolishment of the cardiac vagal response in all cases, P  In our next paper, Domingo Uceda and Xiang-Yang Zhu and associates examined whether progressive increases in pericardial fat volume and inflammation, prospectively dampens the heart rate variability in hypercholesterolemic pigs. The author studied wild type or PCSK9 gain-of-function Ossabaw mini-pigs in-vivo before and after three and six months of a normal diet. Four in the wild type group and six in the PKSK9 group. Or high-fat diet, wild type three, in PCSK9, six.   At diet completion, they found that the hypercholesterolemic PCSK9 had significantly depressed heart rate variability, and both high fat diet groups had higher sympathovagal balance compared to the normal diet. P  In our next paper, Konstantinos Aronis and Rheeda Ali and associates examined myocardial conduction velocity and myocardial fibrosis density on late gadolinium enhanced cardiac magnetic resonance imaging in patients with ischemic cardiomyopathy. The author studied six patients with ischemic cardiomyopathy undergoing VT ablation, and five with structurally normal left ventricle serving as controls. All patients underwent late gadolinium enhanced cardiac magnetic resonance, and electroatomic mapping in sinus rhythm. Median conduction velocity in ischemic cardiomyopathy patients and controls was 0.41 meters per second and 0.65 meters per second respectively. In ischemic cardiomyopathy patients conduction velocity in areas with no visible fibrosis was 0.81 meters per second. For each 25% increase in normalized late gadolinium-enhanced intensity conduction velocity decreased by 1.34 fold. Dense scar areas have an average of 1.97 to 2.66 fold slower conduction velocity compared to areas without dense scar. Ablation lesions that terminate at VT were localized in areas of slow conduction on conduction velocity maps. The authors found that conduction velocity is inversely associated with late gadolinium enhanced cardiac magnetic resonance fibrosis density in patients with ischemic cardiomyopathy.   In our next paper, Bence Hegyi and associates examined whether the IKR current or the sodium L-type current play counterbalancing roles in the ventricular action potential. The authors found that a comparable amount of net charge carried by these two currents during the physiological action potential, suggesting that the outward potassium current via IKR and the inward sodium current via the sodium L-type current are in balance during physiological repolarization. These two current integrals in control myocytes were highly correlated, but this close correlation was lost in heart failure myocytes. Pretreatment with E-4031 to block IKR mimicking long QT syndrome 2, or ATX II to impair a sodium channel inactivation mimicking long QT3 prolong the action potential duration. However, using GS-967 to inhibit sodium L-type current sufficiently restored action potential control to control in both cases.   Furthermore, the sodium L-type inhibition significantly reduced the beat to beat and short-term variabilities of action potential duration. Sodium L-type current inhibition also restored action potential duration in repolarization stability in heart failure. Conversely, pretreatment with GS-967 shortened action potential duration mimicking short QT syndrome and E-4031 reverted APD shortening. Furthermore, the amplitude of action potential alternans occurring at high pacing frequency was decreased by sodium L-type inhibition, increased by IKR inhibition and restored by a combination of sodium L-type and IKR inhibitions. The author suggests that targeting these two ionic currents to normalize or balance may have significant therapeutic potential in heart diseases with repolarization abnormalities.   In our next paper, Derek Chew and associates examine the impact of the duration between first diagnosis of atrial fibrillation and ablation or diagnosis to ablation time on AF recurrence following catheter ablation by conducting a systematic review and meta analysis of observational studies. They found six studies that met inclusion criteria with a total of 4,950 participants undergoing atrial fibrillation ablation for symptomatic AF. A shorter diagnosis to ablation time of one year or less was associated with a lower relative risk of AF recurrence compared to diagnose to the ablation time greater than one year. Relative risk 0.73 P  The authors concluded that the duration between time to first day of AF and AF ablation is associated with an increased likelihood of atrial fibrillation ablation procedural success.   In a research letter by Kapuaola Gellert and associates, 48 hour continuous ECG was found to have an association between sleep apnea and atrial fibrillation in the community-based population study, the ARIC study.   In a special report, Francesco Notaristefano reported that the risk of device pocket hematoma 10 days after CIED surgery showed an independent association with the type of interventional procedure such as device implementation, odds ratio 3.5, implantable cardioverter defibrillator 4.4, cardiac resynchronization therapy, odds ratio 11.7, and antithrombotic treatment, but not with novel oral anticoagulants.   In an interesting review article Nicholas Tan and associates describe the current and future perspectives of left bundle branch block.   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.   Copyright American Heart Association 2020.

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Each podcast will include key highlights from the journal's current issue and a report on new research published in the field of arrhythmia and electrophysiology.

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