Early Impact of Proton Beam Therapy on Electrophysiological Characteristics in a Porcine Model.

BACKGROUND: Particle therapy is a noninvasive, catheter-free modality for cardiac ablation. We previously demonstrated the efficacy for creating ablation lesions in the porcine heart. Despite several earlier studies, the exact mechanism of early biophysical effects of proton and photon beam delivery on the myocardium remain incompletely resolved. METHODS: Ten normal and 9 infarcted in situ porcine hearts received proton beam irradiation (40 Gy) delivered to the left ventricular myocardium with follow-up for 8 weeks. High-resolution electroanatomical mapping of the left ventricular was performed at baseline and follow-up. Bipolar voltage amplitude, conduction velocity, and connexin-43 were determined within the irradiated and nonirradiated areas. RESULTS: The irradiated area in normal hearts showed a significant reduction of bipolar voltage amplitude (10.1±4.9 mV versus 5.7±3.2, P<0.0001) and conduction velocity (85±26 versus 55±13 cm/s, P=0.03) beginning at 4 weeks after irradiation. In infarcted myocardium after irradiation, bipolar voltage amplitude of the infarct scar (2.0±2.9 versus 0.8±0.7 mV, P=0.008) was significantly reduced as well as the conduction velocity in the infarcted heart (43.7±15.7 versus 26.3±11.4 cm/s, P=0.02). There were no significant changes in bipolar voltage amplitude and conduction velocity in nonirradiated myocardium. Myocytolysis, capillary hyperplasia, and dilation were seen in the irradiated myocardium 8 weeks after irradiation. Active caspase-3 and reduction of connexin-43 expression began in irradiated myocardium 1 week after irradiation and decreased over 8 weeks. CONCLUSIONS: Irradiation of the myocardium with proton beams reduce connexin-43 expression, conduction velocity, and bipolar conducted electrogram amplitude in a large porcine model. The changes in biomarkers preceded electrophysiological changes after proton beam therapy.

Bipolar Electroporation Across the Interventricular Septum: Electrophysiological, Imaging, and Histopathological Characteristics.

BACKGROUND: Pulsed electric field (PEF) ablation is an emerging modality for the treatment of cardiac arrhythmias. Data regarding effects on the interventricular septum are limited, and the optimal delivery protocol and electrode configuration remain undefined. OBJECTIVES: This study sought to evaluate the electrophysiological, imaging, and histological characteristics of bipolar direct-current PEF delivered across the interventricular septum. METHODS: PEF was applied between identical solid-tip ablation catheters positioned on either side of the septum in a chronic canine model. Intracardiac and surface electrophysiological data were recorded following delivery. In 4 animals, cardiac magnetic resonance (CMR) was performed early (6 ± 2 days) and late (30 ± 2 days) postablation. After 4 weeks of survival, cardiac specimens were sectioned for histopathological analysis. RESULTS: In 8 canines, PEF was delivered in 27 separate septal sites (45 ± 17 J/site) with either microsecond or nanosecond PEF. Acute complications included transient complete atrioventricular block in 5 animals (63%) after delivery at the anterobasal septum, with right bundle branch block persisting in 3 (38%). Ventricular fibrillation occurred in 1 animal during microsecond but not nanosecond PEF. Postprocedural CMR showed prominent edema and significant left ventricular systolic dysfunction, which recovered with late imaging. At 4 weeks, 36 individual well-demarcated lesions were demonstrated by CMR and histopathology. Lesion depth measured by histology was 2.6 ± 2.1 mm (maximum 10.9 mm and near transmural). CONCLUSIONS: Bipolar PEF ablation of the interventricular septum is feasible and can produce near transmural lesions. Myocardial stunning, edema, and conduction system injury may occur transiently. Further studies are required to optimize safe delivery and efficacious lesions.

Open-chest Pulsed Electric Field Ablation of Cardiac Ganglionated Plexi in Acute Canine Models.

This study aimed to evaluate the safety and acute effect on markers of cardiac autonomic tone following pulsed electric fields (PEFs) delivered to epicardial ganglionated plexi (GP) during a cardiac surgical procedure. Ablation of GP as a treatment for atrial fibrillation (AF) has shown promise, but thermal ablation energy sources are limited by the risk of inadvertent collateral tissue injury. In acute canine experiments, median sternotomy was performed to facilitate the identification of 5 epicardial GP regions using an anatomy-guided approach. Each site was targeted with saline-irrigated PEF (1000 V, 100 µs, 10 electrocardiogram [ECG]-synchronized pulse sequences). Atrial effective refractory period (AERP) and local electrogram (EGM) amplitude were measured before and after each treatment. Histology was performed on samples from treatment-adjacent structures. In 5 animals, 30 (n = 2) and 60 (n = 3) pulses were successfully delivered to each of the 5 target sites. There was no difference in local atrial EGM amplitude before and after PEF application at each site (1.83 ± 0.41 vs. 1.92 ± 0.53 mV, P = .72). The mean AERP increased from 97 ± 15 ms at baseline to 115 ± 7 ms following treatment at all sites (18.6% increase; 95% confidence interval, 1.9-35.2; P = .037). There were no sustained ventricular arrhythmias or acute evidence of ischemia following delivery. Histology showed complete preservation of adjacent atrial myocardium, phrenic nerves, pericardium, and esophagus. Use of PEF to target regions rich in cardiac GP in open-chest canine experiments was feasible and effective at acutely altering markers of cardiac autonomic tone.

Ventricular nanosecond pulsed electric field delivery using active fixation leads: a proof-of-concept preclinical study.

BACKGROUND: Mid-myocardial ventricular arrhythmias are challenging to treat. Cardiac electroporation via pulsed electric fields (PEFs) offers significant promise. We therefore tested PEF delivery using screw-in pacemaker leads as proof-of-concept. METHODS: In 5 canine models, we applied nanosecond PEF (pulse width 300 ns) across the right ventricular (RV) septum using a single lead bipolar configuration (n = 2) and between two leads (n = 3). We recorded electrograms (EGMs) prior to, immediately post, and 5 min after PEF. Cardiac magnetic resonance imaging (cMRI) and histopathology were performed at 2 weeks and 1 month. RESULTS: Nanosecond PEF induced minimal extracardiac stimulation and frequent ventricular ectopy that terminated post-treatment; no canines died with PEF delivery. With 1 lead, energy delivery ranged from 0.64 to 7.28 J. Transient ST elevations were seen post-PEF. No myocardial delayed enhancement (MDE) was seen on cMRI. No lesions were noted on the RV septum at autopsy. With 2 leads, energy delivery ranged from 56.3 to 144.9 J. Persistent ST elevations and marked EGM amplitude decreases developed post-PEF. MDE was seen along the septum 2 weeks and 1 month post-PEF. There were discrete fibrotic lesions along the septum; pathology revealed dense connective tissue with < 5% residual cardiomyocytes. CONCLUSIONS: Ventricular electroporation is feasible and safe with an active fixation device. Reversible changes were seen with lower energy PEF delivery, whereas durable lesions were created at higher energies. Central illustration: pulsed electric field delivery into ventricular myocardium with active fixation leads.

Radiofrequency ablation of the cavotricuspid isthmus for management of atrial flutter in patients with congenital heart disease after tricuspid valve surgery: A single-center experience.

BACKGROUND: Typical atrial flutter involving the cavotricuspid isthmus (CTI) is the most common reentrant arrhythmia in congenital heart disease and ablation is effective in its management. However, congenital heart disease patients often require surgical interventions on their tricuspid valve that utilize prosthetic material, making CTI ablation technically challenging. OBJECTIVE: To describe the techniques and outcomes of CTI ablation in the presence of prior tricuspid valve repair or replacement. METHODS: We included all patients who had undergone tricuspid valve repair utilizing an annuloplasty ring or tricuspid valve replacement who underwent CTI ablation for treatment of atrial arrhythmias between 2005 and 2017. Acute procedural success was defined as demonstration of bidirectional conduction block across the CTI. Long-term success was defined as lack of arrhythmia recurrence on monitoring or related symptoms. RESULTS: Sixteen patients met the inclusion criteria. Twelve (75%) patients had Ebstein's anomaly, 14 (88%) patients had a prosthetic tricuspid valve, and 2 (12%) patients had annuloplasty ring. Acute success was achieved in all cases, with no complications. Radiofrequency ablation was required on the ventricular side in 9 (56%) patients. In 1 case, ablation in the small cardiac vein was required. All patients remained free from atrial flutter during 18 months follow-up (range, 1-101 months). CONCLUSION: Our study demonstrates the safety and efficacy of catheter ablation of the CTI in the presence of a tricuspid annuloplasty ring or a prosthetic tricuspid valve. This may require ablation from the ventricular side of the valve to target atrial tissue rendered inaccessible as a result of tricuspid valve surgery.

Anatomy and Physiologic Roles of the Left Atrial Appendage: Implications for Endocardial and Epicardial Device Closure.

The left atrial appendage has been implicated as a major nidus for thrombus formation, particularly in atrial fibrillation. This discovery has prompted substantial interest in the development of left atrial appendage exclusion devices aimed at decreasing systemic thromboembolism risk. Its deceptively simple appearance belies the remarkable complexity that characterizes its anatomy and physiology. We highlight the key anatomic features and variations of the left atrial appendage as well as its relationships with surrounding structures. We also summarize crucial anatomic factors that should be taken into account by the interventional cardiologist when planning for or performing left atrial appendage exclusion procedures.

Noninvasive blood potassium measurement using signal-processed, single-lead ecg acquired from a handheld smartphone.

OBJECTIVE: We have previously used a 12-lead, signal-processed ECG to calculate blood potassium levels. We now assess the feasibility of doing so with a smartphone-enabled single lead, to permit remote monitoring. PATIENTS AND METHODS: Twenty-one hemodialysis patients held a smartphone equipped with inexpensive FDA-approved electrodes for three 2min intervals during hemodialysis. Individualized potassium estimation models were generated for each patient. ECG-calculated potassium values were compared to blood potassium results at subsequent visits to evaluate the accuracy of the potassium estimation models. RESULTS: The mean absolute error between the estimated potassium and blood potassium 0.38±0.32 mEq/L (9% of average potassium level) decreasing to 0.6 mEq/L using predictors of poor signal. CONCLUSIONS: A single-lead ECG acquired using electrodes attached to a smartphone device can be processed to calculate the serum potassium with an error of 9% in patients undergoing hemodialysis. SUMMARY: A single-lead ECG acquired using electrodes attached to a smartphone can be processed to calculate the serum potassium in patients undergoing hemodialysis remotely.

Wellens Syndrome with Syncope but Not Chest Pain.

We report the case of a woman in her 70s presenting to the emergency department with syncope, troponemia, and an electrocardiogram with deep symmetric T-wave inversions in V2 and V3 and prolonged QTc. Her presentation was concerning for acute coronary syndrome, Wellens syndrome in particular, given the elevated troponin levels, lack of ST segment changes, and characteristic T-wave findings. The diagnosis was confirmed with angiography that showed a critical left anterior descending (LAD) artery occlusion. Since myocardial infarction does not typically present with syncope, we explored the differential diagnoses for T-wave inversions, which include electrolyte abnormalities, medications, intracranial hemorrhage, pulmonary embolism, and other cardiac diseases that were ruled out in our patient. We also explored the pathophysiology leading to syncope in the setting of acute myocardial infarction including arrhythmias and exaggerated neurally mediated response. Our patient received two drug-eluting stents to the LAD artery and was started on dual antiplatelet therapy, beta-blockers, and an angiotensin-converting enzyme inhibitor.