Sauer, William H.

ABSTRACT Background Pulsed‐field ablation (PFA) offers myocardial selectivity with minimal thermal injury, but depth for ventricular lesions may be insufficient or heterogeneous at clinically tolerable field strengths. Calcium electroporation—local calcium chloride (CaCl₂) infusion after PFA—may amplify electroporation‐mediated cell death while maintaining low energy settings. Objective To determine whether immediate post‐PFA CaCl₂ infusion enhances acute and chronic ventricular lesion formation in vivo. Methods Nine swine underwent focal ventricular PFA (750–1000 V, biphasic, 20 μs × 50 pulses, 200 ms interpulse) via an irrigated focal catheter and benchtop electroporator. Immediately post‐PFA, lesions were randomized to saline, 0.2 g Ca, or 0.4 g Ca infused locally through the catheter tip. Acute hearts were explanted for TTC analysis; surviving animals were studied at 7 days for chronic lesion geometry. Results Among 41 acute lesions (17 control, 12 Ca 0.2 g, 12 Ca 0.4 g), Ca 0.4 g increased dark‐zone depth (3.5 ± 1.4 vs. 2.3 ± 0.8 mm; p = 0.038) and pale‐zone depth (2.6 ± 1.3 vs. 1.3 ± 0.8 mm; p = 0.011) versus control. At 7 days ( n = 33 lesions), Ca 0.4 g produced larger scars than control (width 11.6 ± 2.1 vs. 10.0 ± 1.9 mm; p = 0.027; depth 4.2 ± 1 vs. 3.0 ± 0.8 mm; p < 0.001; volume 193.6.4 ± 82.3 vs. 109.4 ± 48.2 mm³; p = 0.001). Conclusions Local CaCl₂ infusion after ventricular PFA significantly augments acute electroporation effect and chronic lesion size at low output, supporting facilitated PFA as a strategy for deeper, more durable ventricular ablation.

Abstract Background Cardiac sarcoidosis (CS) is an infiltrative cardiomyopathy characterized by myocardial granulomatous inflammation, leading to conduction system abnormalities and ventricular arrhythmias. Cardiac resynchronization therapy (CRT) outcomes in CS patients are controversial. The efficacy of CRT with left bundle branch area pacing (LBBAP) in these patients has not yet been elucidated. Objective To evaluate electrocardiographic, echocardiographic and long-term clinical outcomes after CRT with LBBAP in CS patients. Methods In this retrospective multicenter study, conducted between June 2020 and March 2024, patients with a histopathologically confirmed diagnosis of CS with an indication for CRT were included in the analysis. The primary outcome was a composite of all-cause mortality, heart failure related hospitalizations, implantable cardioverter defibrillator shocks and requirement of left ventricular assist device/heart transplant. The primary safety outcome was procedure-related complications. Secondary outcomes included pre- and post-procedural electrocardiographic and echocardiographic parameters and change in NYHA functional class. Results A total of 16 patients were included in the analysis (mean age 66.2 ± 9.4 years; 62.5% female; body mass index 30.4 ± 8.5 kg/m2). Four patients (25%) had isolated CS. The median follow-up was 579 [Q1: 295.5 – Q3: 797.5] days. Five patients (31.25%) experienced the composite outcome. Among these, two patients (12.5%) had acute heart failure related hospitalizations, two patients (12.5%) died due to severe pulmonary hypertension and sepsis complicated by cardiorenal syndrome, respectively; and one patient (6.25%) presented an episode of ventricular tachycardia that was successfully terminated with an implantable cardioverter defibrillator shock. No patients required advanced heart failure therapies. There were no procedure-related complications. There was a significant improvement in paced QRS duration (Pre 156.8 ± 36.2 vs. Post 128.3 ± 22.3 milliseconds, p=0.003), left ventricular ejection fraction (Pre 36.5 ± 10.6% vs. Post 50.4 ± 12.2%, p&lt;0.001), left ventricular end systolic diameter (Pre 52 [39.5 – 84.3] vs. Post 41 [29 – 72] millimeters, p=0.011) and left ventricular end diastolic diameter (Pre 66.7 [48 – 159] vs. Post 61 [44 – 135] millimeters, p=0.023). Ten (62.5%) patients exhibited an improvement ≥ I in NYHA functional class post procedure. Conclusion In CS patients, CRT with LBBAP was associated with significant improvements in electrocardiographic and echocardiographic parameters, as well as NYHA functional class, alongside favorable long-term clinical outcomes by optimizing interventricular dyssynchrony.Graphical abstract ECG and Echo parameters

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.

AbstractIntroductionPulsed field ablation (PFA) has emerged as an innovative therapy for cardiac arrhythmias. Drawing parallels with PFA's application in solid tumors, calcium chloride (CaCl2) as an adjuvant therapy, known as calcium electroporation, may amplify PFA's apoptotic effects. We propose that PFA in the atrium could enhance calcium uptake through PFA‐created pores, thereby increasing ablation efficacy even at reduced power levels by exploiting PFA's permeabilization effects.MethodsWe conducted in vivo ablations on the atria of seven pigs using low PFA power (250 V, 20 μs for 50 pulses at 200 ms intervals). Post‐PFA, we randomly administered an infusion of either 200 mg/2 ml CaCl2 (calcium group) or saline (control) directly to the ablation site via the catheter tip. We evaluated reduction in electrogram voltage amplitude, electrocardiography (ECG) parameters, ablation lesion parameters, and histology after PFA.ResultsNineteen lesions from control and calcium groups were examined. Control lesions showed no voltage decrease post‐PFA, whereas calcium‐treated lesions exhibited a significant voltage reduction. Gross pathology indicated marked differences in maximum lesion surface diameter, depth, and volume between the lesion groups. Histologically, calcium group lesions were characterized by a more severe acute PFA response with contraction band necrosis, myocytolysis and nuclear pyknosis in adjacent myocardium, in addition to microhemorrhages.ConclusionInfusing calcium chloride locally after PFA markedly improves the immediate efficacy of electroporation in porcine atria. This study suggests that calcium electroporation could bolster PFA outcomes without higher energy levels, potentially diminishing associated risks. These preliminary findings warrant further research into the long‐term efficacy and potential clinical application of calcium electroporation in PFA.

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.

Despite the global COVID-19 pandemic, during the past 2 years, there have been numerous advances in our understanding of arrhythmia mechanisms and diagnosis and in new therapies. We increased our understanding of risk factors and mechanisms of atrial arrhythmias, the prediction of atrial arrhythmias, response to treatment, and outcomes using machine learning and artificial intelligence. There have been new technologies and techniques for atrial fibrillation ablation, including pulsed field ablation. There have been new randomized trials in atrial fibrillation ablation, giving insight about rhythm control, and long-term outcomes. There have been advances in our understanding of treatment of inherited disorders such as catecholaminergic polymorphic ventricular tachycardia. We have gained new insights into the recurrence of ventricular arrhythmias in the setting of various conditions such as myocarditis and inherited cardiomyopathic disorders. Novel computational approaches may help predict occurrence of ventricular arrhythmias and localize arrhythmias to guide ablation. There are further advances in our understanding of noninvasive radiotherapy. We have increased our understanding of the role of His bundle pacing and left bundle branch area pacing to maintain synchronous ventricular activation. There have also been significant advances in the defibrillators, cardiac resynchronization therapy, remote monitoring, and infection prevention. There have been advances in our understanding of the pathways and mechanisms involved in atrial and ventricular arrhythmogenesis.

Cardiac sarcoidosis is a component of an often multiorgan granulomatous disease of still uncertain cause. It is being recognized with increasing frequency, mainly as the result of heightened awareness and new diagnostic tests, specifically cardiac magnetic resonance imaging and 18 F-fluorodeoxyglucose positron emission tomography scans. The purpose of this case-based review is to highlight the potentially life-saving importance of making the early diagnosis of cardiac sarcoidosis using these new tools and to provide a framework for the optimal care of patients with this disease. We will review disease mechanisms as currently understood, associated arrhythmias including conduction abnormalities, and atrial and ventricular tachyarrhythmias, guideline-directed diagnostic criteria, screening of patients with extracardiac sarcoidosis, and the use of pacemakers and defibrillators in this setting. Treatment options, including those related to heart failure, and those which may help clarify disease mechanisms are included.