Harry van Wessel

Practical and conceptual limitations of tissue Doppler imaging to predict reverse remodelling in cardiac resynchronisation therapy

Recent, conflicting results about the use of tissue Doppler imaging derived (TDI‐) asynchrony indices to predict reverse remodelling after cardiac resynchronisation therapy (CRT) have raised questions about their physiological meaning and methodological limitations.

Can optimization of pacing settings compensate for a non-optimal left ventricular pacing site?

AIMS Optimal left ventricular (LV) lead position improves the response to cardiac resynchronization therapy (CRT). However, in some patients it is not possible to position the LV lead at an optimal pacing site. The aim of this study was to determine whether optimization of the pacing settings atrioventricular delay (AVD) and interventricular delay (VVD) can compensate for a non-optimal LV pacing site. METHODS AND RESULTS In 16 patients with heart failure [New York Heart Association class III (13) or IV (3), median QRS duration of 172 ms and median LV ejection fraction of 20%] the acute haemodynamic effect of biventricular pacing was assessed at > or =2 pacing sites by the increase in maximum rate of LV pressure rise (%dP/dt(max)). At each site the AVD and VVD were optimized. Biventricular pacing with nominal settings at a non-optimal LV pacing site improved dP/dt(max) by 12.8% (-0.5 to 23.2%). This could be further improved by 6.5 percentage points (1.2-13.9) by optimization of pacing settings (P = 0.001) and by 9.9 percentage points (3.7-13.3, P = 0.004) by optimization of pacing site. Optimization of the LV pacing site and pacing settings together improved %dP/dt(max) by 16.2 per cent points (10.0-21.8, P < 0.001). CONCLUSION Optimization of the AVD and VVD can partly compensate for a non-optimal LV pacing site. However, a combination of an optimal LV pacing site and optimized pacing settings gives the best acute haemodynamic response.

Feasibility of Electroporation for the Creation of Pulmonary Vein Ostial Lesions

Feasibility of Electroporation. Introduction: There is an obvious need for a better energy source for pulmonary vein (PV) antrum isolation.

Minimal coronary artery damage by myocardial electroporation ablation.

AIMS Radiofrequency catheter ablation is a successful treatment for cardiac arrhythmias, but may lead to major complications such as permanent coronary damage. Irreversible electroporation (IRE) is a new non-thermal ablation modality, but its effect on coronary arteries is still unknown. METHODS AND RESULTS In a porcine model, epicardial IRE lesions were created at the base of the left ventricle in four hearts (group A) and directly on the left anterior descending artery (LAD) in five hearts (group B). After 3 weeks, coronary arteries inside IRE lesions and in apparently undamaged myocardium next to the lesions were (immuno-)histologically studied. Two untreated hearts served as controls. Coronary damage was defined as intimal hyperplasia. Left anterior descending artery angiograms were obtained before ablation, directly after ablation, and before termination in group B. In group A, 103 arterial branches were studied. Of these, 5 of 56 arterial branches inside lesions and 1 of 47 outside lesions showed intimal hyperplasia, but all had <50% area stenosis. Targeted LADs (group B) did not reveal intimal hyperplasia and angiograms showed no signs of stenosis. Expression of connective tissue growth factor was observed in the scar tissue, but not in the fibrotic tissue directly around the arteries, confirming that the arteries are indeed spared from tissue damage and remodelling. CONCLUSION Coronary arteries remain free of clinically relevant damage 3 weeks after epicardial IRE ablation, even amid very large myocardial lesions. This suggests that IRE ablation can be applied safely near or even on coronary arteries. With IRE ablation, arterial blood flow does not appear to affect lesion formation.

Safety and Feasibility of Closed Chest Epicardial Catheter Ablation Using Electroporation

Background—Permanent coronary artery damage is a hazardous complication of epicardial radiofrequency ablation. Irreversible electroporation (IRE) is a promising nonthermal ablation modality able to create deep myocardial lesions. We investigated the effects of epicardial IRE on luminal coronary artery diameter and lesion depth. Methods and Results—In 5 pigs (60–75 kg), the pericardium was exposed using surgical subxiphoidal epicardial access. A custom deflectable octopolar 12-mm circular catheter with 2-mm ring electrodes was introduced in the pericardium via a steerable sheath. After coronary angiography (CAG), the proximal, mid, and distal left anterior descending, and circumflex coronary arteries were targeted with a single, cathodal 200 J application. CAG was repeated after IRE and after 3 months follow-up. Using quantitative CAG, the minimal luminal diameter at the lesion site was compared with the average of the diameters just proximal and distal to that lesion. Intimal hyperplasia and lesion size were measured histologically. CAG directly postablation demonstrated short-lasting luminal narrowing with normalization in the targeted area, suggestive of coronary spasm. After 3 months, all CAGs were identical to preablation CAGs: mean reference luminal diameter was 2.2±0.3 mm, mean luminal diameter at the lesion site was 2.1±0.3 mm (P=0.35). Average intimal hyperplasia in all arteries was 2±4%. Median lesion depth was 6.4±2.6 mm. Conclusions—Luminal coronary artery diameter remained unaffected 3 months after epicardial IRE, purposely targeting the coronary arteries. IRE can create deep lesions and is a safe modality for catheter ablation on or near coronary arteries.

Myocardial Lesion Depth With Circular Electroporation Ablation

Background—Recently, we demonstrated the feasibility and safety of circular electroporation ablation in porcine pulmonary vein ostia, but the relationship between the magnitude of the application and lesion dimensions is still unknown. Methods and Results—An in vivo porcine study was performed on left ventricular epicardium submerged under 10 mm of blood, using devices that mimic a 20-mm-diameter 7F circular ablation catheter. Model D contained 10 separate electrodes, whereas model M consisted of 1 circular electrode. Ablations were performed at 50, 100, and 200 J with model D and at 100 J with model M. Lesion dimensions were measured after 3-week survival. All applications resulted in smooth voltage waveforms demonstrating the absence of vapor globe formation, arcing, and a pressure wave. Applications up to 100 J with model D resulted in separate lesions under the electrodes. At 200 J, continuous deep circular lesions were created despite the use of separate electrodes. There was a significant relationship between applied current and median lesion depth, with a slope of 0.17 mm/A. At 100 J, there was no difference in lesion depth or width between models D and M. The electrodes and ablation site directly after ablation showed no signs of thermal damage. Conclusions—In an epicardial porcine model with blood around the application site, continuous circular lesions, deep enough for electric pulmonary vein isolation, were created with a single circular 200-J application. Lesions were continuous despite the use of separate electrodes. Lesion depth increased with the magnitude of the application.

Pulmonary vein stenosis after catheter ablation: electroporation versus radiofrequency.

Background— Radiofrequency ablation inside pulmonary vein (PV) ostia can cause PV stenosis. A novel alternative method of ablation is irreversible electroporation, but the long-term response of PVs to electroporation ablation is unknown. Methods and Results— In ten 6-month-old pigs (60–75 kg), the response of PVs to circular electroporation and radiofrequency ablation was compared. Ten consecutive, nonarcing, electroporation applications of 200 J were delivered 5 to 10 mm inside 1 of the 2 main PVs, using a custom-deflectable, 18-mm circular decapolar catheter. Inside the other PV, circular radiofrequency ablation was performed using 30 W radiofrequency applications via an irrigated 4-mm ablation catheter. PV angiograms were made before ablation, immediately after ablation, and after 3-month survival. PV diameters and heart size were measured. With electroporation ablation, PV ostial diameter decreased 11±10% directly after ablation, but had increased 19±11% after 3 months. With radiofrequency ablation, PV ostial diameter decreased 23±15% directly after ablation and remained 7±17% smaller after 3 months compared with preablation diameter despite a 21±7% increase in heart size during aging from 6 to 9 months. Conclusions— In this porcine model, multiple circumferential 200-J electroporation applications inside the PV ostia do not affect PV diameter at 3-month follow-up. Radiofrequency ablation inside PV ostia causes considerable PV stenosis directly after ablation, which persists after 3 months.Background—Radiofrequency ablation inside pulmonary vein (PV) ostia can cause PV stenosis. A novel alternative method of ablation is irreversible electroporation, but the long-term response of PVs to electroporation ablation is unknown. Methods and Results—In ten 6-month-old pigs (60–75 kg), the response of PVs to circular electroporation and radiofrequency ablation was compared. Ten consecutive, nonarcing, electroporation applications of 200 J were delivered 5 to 10 mm inside 1 of the 2 main PVs, using a custom-deflectable, 18-mm circular decapolar catheter. Inside the other PV, circular radiofrequency ablation was performed using 30 W radiofrequency applications via an irrigated 4-mm ablation catheter. PV angiograms were made before ablation, immediately after ablation, and after 3-month survival. PV diameters and heart size were measured. With electroporation ablation, PV ostial diameter decreased 11±10% directly after ablation, but had increased 19±11% after 3 months. With radiofrequency ablation, PV ostial diameter decreased 23±15% directly after ablation and remained 7±17% smaller after 3 months compared with preablation diameter despite a 21±7% increase in heart size during aging from 6 to 9 months. Conclusions—In this porcine model, multiple circumferential 200-J electroporation applications inside the PV ostia do not affect PV diameter at 3-month follow-up. Radiofrequency ablation inside PV ostia causes considerable PV stenosis directly after ablation, which persists after 3 months.

Complex fractionated electrograms in the right atrial free wall and the superior/posterior wall of the left atrium are affected by activity of the autonomic nervous system.

CFAEs and Autonomic Nervous System. Background: Complex fractionated atrial electrograms (CFAEs) are supposed to be related to structural and electrical remodeling. Animal studies suggest a role of the autonomic nervous system (ANS). However, this has never been studied in humans.

Myocardial Lesion Size After Epicardial Electroporation Catheter Ablation After Subxiphoid Puncture

Background—Irreversible electroporation is a promising nonthermal ablation modality able to create deep myocardial lesions. We investigated lesion size after epicardial electroporation catheter ablation with various energy levels after subxiphoid pericardial puncture. Methods and Results—In six 6-month-old pigs (60–75 kg), a custom deflectable octopolar 12-mm circular catheter with 2-mm ring electrodes was introduced via a deflectable sheath after pericardial access by subxiphoid puncture. Nonarcing, nonbarotraumatic, cathodal 50, 100, and 200 J electroporation applications were delivered randomly on the basal, mid and lateral left ventricle. After 3-month survival, myocardial lesion size and degree of intimal hyperplasia of the coronary arteries were analyzed histologically. Five animals survived the follow-up without complications and 1 animal died of shock after the subxiphoid puncture. At autopsy, whitish circular scars with indentation of the epicardium could be identified. Average lesion depths of the 50-, 100-, and 200-J lesions were 5.0±2.1, 7.0±2.0, and 11.9±1.5 mm, respectively. Average lesion widths of the 50-, 100-, and 200-J lesions were 16.6±1.1, 16.2±4.3, and 19.8±1.8 mm, respectively. In the 100- and 200-J cross sections, transmural left ventricular lesions and significant tissue shrinkage were observed. No intimal hyperplasia of the coronary arteries was observed. Conclusions—Epicardial electroporation ablation after subxiphoid pericardial puncture can create deep, wide, and transmural ventricular myocardial lesions. There is a significant relationship between the amounts of electroporation energy delivered epicardially and lesion size in the absence of major adverse events.

Acute and Long-Term Effects of Full-Power Electroporation Ablation Directly on the Porcine Esophagus

Background— Esophageal ulceration and fistula are complications of pulmonary vein isolation using thermal energy sources. Irreversible electroporation is a novel, nonthermal ablation modality for pulmonary vein isolation. A single 200 J application can create deep myocardial lesions. Acute and chronic effects of this new energy source on the esophagus are unknown. Methods and Results— In 8 pigs (±70 kg), the suprasternal esophagus was surgically exposed. A linear suction device with a single 35-mm long and 6-mm wide protruding linear electrode inside a plastic suction cup was used for ablation. Single, nonarcing, nonbarotraumatic, cathodal 100 and 200 J applications were delivered at 2 different sites on the anterior esophageal adventitia. No proton-pump inhibitors were administered during follow-up. Esophagoscopy was performed at days 2 and 7. After euthanasia at day 60, the esophagus was evaluated visually and histologically. All ablations were uneventful. Esophagoscopy at day 2 showed small white densities in the ablated areas, which appeared to be small intraepithelial vesicles. No epithelial erythema, erosions, or ulcerations were seen. At day 7, all densities had disappeared, and all esophaguses appeared completely normalized. After euthanasia, there were no macroscopically visible lesions on the adventitia or epithelium. Histologically, a small scar was observed at the outer part of the muscular layer, whereas the mucosa and submucosa were normal. Conclusions— Esophageal architecture remains unaffected 2 months after irreversible electroporation, purposely targeting the adventitia. Irreversible electroporation seems to be a safe modality for catheter ablation near the esophagus.