Nguyen, Duy T.

Backround: Advances in surgical and medical care of children born with congenital heart disease (CHD) has improved survival into adulthood. However, cardiac and non-cardiac morbidity and mortality remain common in adults with CHD (ACHD). We present the causes and predictors of mortality in a large cohort of ACHD patients from the USA. Methods/Approach: We conducted a retrospective review of ACHD patients followed at Mayo Clinic between 1992 - 2024. Mortality was ascertained using the Accruint national data base. Clinical characteristics and primary cause of death were identified from the electronic record. Kaplan-Meier (KM) survival analysis was performed to compare overall survival stratified by CHD severity. Cox proportional hazards regression was used to identify independent predictors of mortality. Results/Data: Amongst 9160 ACHD patients (mean age 38±16y at first visit, 51% males, 23% simple, 59% moderate and 18% severe CHD), mortality occurred in 1430(16%) patients during a mean follow-up of 11±7y. The mean age at death was 68±17 y, 58±17y, and 45±15y in mild, moderate and severe ACHD. KM analysis of survival and cause of death stratified by CHD severity are presented in Figures 2 and 3 respectively. Cause of death could not be ascertained in 33%%. Amongst those with a known cause of death, the proportion of non-cardiac death increased with decreasing severity of CHD. HF death and sudden cardiac death occurred in 11% and 19%. Infection, malignancy and chronic respiratory failure were important non-cardiac causes of death. Significant risk factors for mortality included CHD severity, ventricular arrhythmia, heart failure, declining functional capacity, diabetes and chronic kidney disease as presented in the Fig 1. Conclusion(s): Mortality in ACHD patients is associated with CHD severity, heart failure, ventricular arrhythmia and cardiovascular comorbidities. Early recognition and management of these risk factors may improve long-term survival. As patients with ACHD age, management of cardiovascular and noncardiac risk factors will require development of systems of care specific to this vulnerable population.

Background: Patients with repaired Tetralogy of Fallot (TOF) undergoing pulmonary valve replacement (PVR) are at increased risk of major adverse ventricular arrhythmias and related events (MAREs). Perioperative electrophysiological study (EPS) has been used for risk stratification and guiding future management, but these studies are limited by small sample size. Objectives: To perform a systematic review of outcomes of pre-PVR EPS in TOF patients with PVR. Methods: A comprehensive search of PubMed, Embase, Scopus and Google scholar databases was performed per PRISMA 2020 guidelines. Studies on patients with repaired TOF undergoing PVR with perioperative EPS were included. Data were extracted on study design, sample size, EPS outcomes and MAREs during follow-up. Results: A total of 1,528 patients (age: 35.5±3.8 y; 57% male; LVEF: 57.1±1.5%, RVEF: 42.6±1.5%) were included from 12 studies. EPS was performed in 1212/1528 (79.3%), with sustained VT inducibility in 404 (33.3%)-monomorphic VT in 258 (63.8%), while 808 (66.6%) were non- inducible. 8/12 studies reported the type of PVR (transcatheter-36.8%). 174/293 (59.3%) inducible patients had an ablation (9 studies), while ICD (6 studies) was implanted in 70/263 (26.6%). Follow-up EPS (6 studies) showed 35/230 (15.2%) remained inducible. Overall,113 (9.3%) patients experienced MAREs over a median follow-up ranging from 6 months to 6.7 years. Sustained VT (11/12 studies) occurred in 70/1092 (6.4%), appropriate ICD therapy (7/12 studies) in 13/622 (2.1%) and sudden cardiac death (10/12 studies) in 30/906 (3.3%). Five studies provided MARE data stratified by VT inducibility. 12/164 (7.3%) inducible patients experienced MAREs, compared to 2/318 (0.6%) non-inducible patients. Reported risk factors for MAREs included older age at initial repair and PVR, QRS duration (>180ms), LVEF <45%, RVEF <35%, history of syncope, prior palliative shunts and atrial arrhythmias. Some studies identified MRI-derived scar burden, pulmonary annulus size, and RV/LV volume ratios as additional predictors. Conclusion: TOF patients remain at high risk of VA after PVR with 1/10 patients experiencing MAREs. People with inducible VT had a 12-fold greater risk than people who were non-inducible. EPS identifies a subset of TOF patients at higher arrhythmic risk during PVR and supports tailored ablation and ICD strategies. Prospective multicentre studies are needed to optimize integration of EPS and clinical risk models.

BACKGROUND: Catheter ablation of ventricular arrhythmias, one of the most rapidly growing procedures in cardiac electrophysiology, is associated with magnetic resonance imaging–detected brain lesions in more than half of cases. Although a retrograde aortic approach is conventional, modern tools enable entry through a transseptal approach that may avoid embolization of debris from the arterial system. We sought to test the hypothesis that a transseptal puncture would mitigate brain injury compared with a retrograde aortic approach. METHODS: The TRAVERSE trial (Transseptal Versus Retrograde Aortic Ventricular Entry to Reduce Systemic Emboli) was a multicenter randomized controlled comparative effectiveness trial. Patients with left ventricular arrhythmias undergoing catheter ablation procedures were randomly assigned to a transseptal puncture approach compared (1:1) with a retrograde aortic approach. The primary outcome was the presence of an acute brain lesion detected by magnetic resonance imaging. Secondary outcomes included clinically manifest complications, procedural efficacy, and 6-month neurocognitive assessments. RESULTS: Among the 62 patients randomly assigned to a retrograde aortic approach with postoperative brain magnetic resonance imaging, 28 (45%) exhibited an acute brain lesion compared with 19 of the 69 (28%) of those randomized to a transseptal puncture ( P =0.036). No differences in clinically manifest complications or procedural efficacy were observed. More patients in the retrograde aortic arm were categorized as having a high likelihood of cognitive impairment at 6 months (33% compared with 19% of those in the transseptal arm), but substantial loss to follow-up was present. CONCLUSIONS: Among patients undergoing left ventricular catheter ablation procedures, a transseptal approach reduced the risk of acute brain lesions by nearly half compared with a retrograde aortic approach without sacrificing safety or efficacy. Given a likely embolic pathogenesis, the brain magnetic resonance imaging findings may reflect a propensity to other organ damage; these findings may extend to other procedures requiring left ventricular entry. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03946072.

Background: Pulsed field ablation (PFA) is an innovative modality for treating arrhythmias that is mostly non-thermal and renders myocardial tissue non-viable by creating pores in cardiac cell membranes. The impact of contact force (CF) on PFA efficacy is not well characterized. Hypothesis: We hypothesize that, while contact is necessary for PFA, increasing CF will not have a significant effect on in vivo ablation lesion size. Aim: We seek to investigate the effects of CF on acute PFA lesions in a beating porcine heart model. Methods: The ventricles of 7 porcine animals were ablated in vivo with PFA (500V, at 20μs for 50 pulses separated by 200ms) using a focal bipolar irrigated ablation catheter and BTX 830 electroporation generator (Harvard Apparatus). CF was measured before and after each PFA application using CARTO 3. Lesions were divided into standard CF (5-15g), high CF (16-30g), and very high CF (>31g). Results: A total of 46 lesions were analyzed. Gross pathology showed no significant difference in maximum width, lesion depth, and lesion volume between the three groups ( Figure 1A-B ). Linear regression showed a decrease of 0.003 mm in depth (depth = -0.003 × CF + 1.8, R = 0.05), an increase of 0.01 mm in width (width = 0.01 × CF + 5.7, R = 0.09), and a decrease of 0.05 mm 3 in volume (volume = -0.05 × CF + 26.8, R = 0.03) for each additional gram of CF ( Figure 1C ). Conclusion: While contact is necessary, increasing CF did not have a significant effect on in-vivo PFA lesion dimensions in a beating porcine heart model.

Background: Pulsed field ablation (PFA) has emerged as an innovative technology for treating cardiac arrhythmias. PFA increases cell permeability, which can lead to apoptosis. Greater PFA energy may be necessary to ablate ventricular myocardium for ventricular tachycardia circuits, but this carries risks of side effects such as gaseous formation (microbubbles) and hemolysis. Ethanol (EtOH) infusion has been used to ablate pathologic myocardial tissues in hypertrophic cardiomyopathy and for refractory arrhythmias. Hypothesis: We hypothesize that PFA in the ventricle can increase EtOH uptake through PFA-generated pores, thereby enhancing ablation efficacy, even at low powers, by utilizing the cell permeability effects of PFA. Aim: The aim of this study is to investigate the effect of local EtOH infusion after PFA on lesion size in porcine ventricles. Methods: The ventricles of five porcine subjects were ablated in vivo with a PFA low power setting (750 V, at 20 μs for 50 pulses separated by 200 ms) using a focal bipolar irrigated ablation catheter and BTX 830 electroporation generator (Harvard Apparatus). After PFA was performed, 2 ml of 90 % EtOH vs. saline (control) was infused through the catheter tip to the site of ablation. We compared the electrograms voltage amplitude reduction before and after PFA, and the ablation lesion characteristics. Results: A total of 10 lesions in the control group and 9 lesions in the EtOH group were analyzed. For the controls, the voltage after PFA was not reduced. In contrast, for the EtOH group, the voltage after PFA was significantly reduced ( Figure 1A ). On gross pathology, there were significant differences in ablation lesion depths and volumes between the 2 lesion sets ( Figure 1A-B ). Conclusion: Local EtOH infusion after ventricular PFA enhanced acute efficacy of electroporation. Concurrent PFA with local EtOH infusion has the potential to improve efficacy without requiring higher energy parameters, thereby reducing PFA risks. Future studies on chronic efficacy are warranted.

Background: Pulsed field ablation (PFA) is a promising modality for treatment of cardiac arrhythmias. PFA increases cell permeability, thereby promoting cell apoptosis. Although greater PFA energy may produce larger lesions, it also carries risks of side effects such as arcing, hemolysis, and microbubbles. Chemical ablation using ethanol (EtOH), such as with injection of the Vein of Marshall, has been used to treat atrial myocardium for refractory atrial arrhythmias. Hypothesis: We hypothesize that PFA in the atria can increase EtOH uptake through PFA-generated pores, thereby augmenting ablation efficacy by utilizing the cell permeability effects of PFA. Aim: The aim of this study is to investigate the effects of local EtOH infusion after PFA on lesion size in porcine atria. Methods: The atria of five porcine subjects were ablated in vivo with low PFA power settings (250V, at 20μs for 50 pulses separated by 200 ms) using a focal bipolar irrigated ablation catheter and BTX 830 electroporation generator (Harvard Apparatus). After PFA, 2 ml of 90 % EtOH vs. saline (control) was infused through the catheter tip to the site of ablation. We compared electrogram voltage amplitude reduction and ablation lesion parameters before and after PFA. Results: A total of 14 control lesions and 14 EtOH lesions were analyzed. There was significant difference in voltage reduction between two groups ( Figure 1A-B ). On gross pathology, there were significant differences in ablation lesion maximum surface diameter, lesion depth, and volume between the 2 lesion sets ( Figure 1C ). Conclusion: Concurrent EtOH infusion after PFA enhanced acute efficacy of electroporation in porcine atria. Adjuvant therapy has the potential to improve efficacy without requiring higher energy parameters, thereby reducing PFA risks. Further studies to assess chronic efficacy are warranted.

AbstractIntroductionEsophageal injury is a well‐known complication associated with catheter ablation. Though novel methods to mitigate esophageal injury have been developed, few studies have evaluated temperature gradients with catheter ablation across the posterior wall of the left atrium, interstitium, and esophagus.MethodsTo investigate temperature gradients across the tissue, we developed a porcine heart–esophageal model to perform ex vivo catheter ablation on the posterior wall of the left atrium (LA), with juxtaposed interstitial tissue and esophagus. Circulating saline (5 L/min) was used to mimic blood flow along the LA and alteration of ionic content to modulate impedance. Thermistors along the region of interest were used to analyze temperature gradients. Varying time and power, radiofrequency (RF) ablation lesions were applied with an externally irrigated ablation catheter. Ablation strategies were divided into standard approaches (SAs, 10–15 g, 25–35 W, 30 s) or high‐power short duration (HPSD, 10–15 g, 40–50 W, 10 s). Temperature gradients, time to the maximum measured temperature, and the relationship between measured temperature as a function of distance from the site of ablation was analyzed.ResultsIn total, five experiments were conducted each utilizing new porcine posterior LA wall‐esophageal specimens for RF ablation (n = 60 lesions each for SA and HPSD). For both SA and HPSD, maximum temperature rise from baseline was markedly higher at the anterior wall (AW) of the esophagus compared to the esophageal lumen (SA: 4.29°C vs. 0.41°C, p < .0001 and HPSD: 3.13°C vs. 0.28°C, p < .0001). Across ablation strategies, the average temperature rise at the AW of the esophagus was significantly higher with SA relative to HPSD ablation (4.29°C vs. 3.13°C, p = .01). From the start of ablation, the average time to reach a maximum temperature as measured at the AW of the esophagus with SA was 36.49 ± 12.12 s, compared to 16.57 ± 4.54 s with HPSD ablation, p < .0001. Fit to a linear scale, a 0.37°C drop in temperature was seen for every 1 cm increase in distance from the site of ablation and thermistor location at the AW of the esophagus.ConclusionBoth SA and HPSD ablation strategies resulted in markedly higher temperatures measured at the AW of the esophagus compared to the esophageal lumen, raising concern about the value of clinical intraluminal temperature monitoring. The temperature rise at the AW was lower with HPSD. A significant time delay was seen to reach the maximum measured temperature and a modest increase in distance between the site of ablation and thermistor location impacted the accuracy of monitored temperatures.