René van Es

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.

High Resolution Systematic Digital Histological Quantification of Cardiac Fibrosis and Adipose Tissue in Phospholamban p.Arg14del Mutation Associated Cardiomyopathy

Myocardial fibrosis can lead to heart failure and act as a substrate for cardiac arrhythmias. In dilated cardiomyopathy diffuse interstitial reactive fibrosis can be observed, whereas arrhythmogenic cardiomyopathy is characterized by fibrofatty replacement in predominantly the right ventricle. The p.Arg14del mutation in the phospholamban (PLN) gene has been associated with dilated cardiomyopathy and recently also with arrhythmogenic cardiomyopathy. Aim of the present study is to determine the exact pattern of fibrosis and fatty replacement in PLN p.Arg14del mutation positive patients, with a novel method for high resolution systematic digital histological quantification of fibrosis and fatty tissue in cardiac tissue. Transversal mid-ventricular slices (n = 8) from whole hearts were collected from patients with the PLN p.Arg14del mutation (age 48±16 years; 4 (50%) male). An in-house developed open source MATLAB script was used for digital analysis of Massons trichrome stained slides (http://sourceforge.net/projects/fibroquant/). Slides were divided into trabecular, inner and outer compact myocardium. Per region the percentage of connective tissue, cardiomyocytes and fatty tissue was quantified. In PLN p.Arg14del mutation associated cardiomyopathy, myocardial fibrosis is predominantly present in the left posterolateral wall and to a lesser extent in the right ventricular wall, whereas fatty changes are more pronounced in the right ventricular wall. No difference in distribution pattern of fibrosis and adipocytes was observed between patients with a clinical predominantly dilated and arrhythmogenic cardiomyopathy phenotype. In the future, this novel method for quantifying fibrosis and fatty tissue can be used to assess cardiac fibrosis and fatty tissue in animal models and a broad range of human cardiomyopathies.

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.

Epicardial linear electroporation ablation and lesion size

BACKGROUND Electroporation can be used as a nonthermal method to ablate myocardial tissue. However, like with all electrical ablation methods, determination of the energy supplied into the myocardium enhances the clinically required controllability over lesion creation. OBJECTIVE To investigate the relationship between the magnitude of epicardial electroporation ablation and the lesion size using an electrically isolating linear suction device. METHODS In 5 pigs (60-75 kg), the pericardium was opened after medial sternotomy. A custom linear suction device with a single 35 × 6-mm electrode inside a 42-mm-long and 7-mm-wide plastic suction cup was used for electroporation ablation. Single cathodal applications of 30, 100, or 300 J were delivered randomly at 3 different epicardial left ventricular sites. Coronary angiography was performed before ablation, immediately after ablation, and after 3 months survival. Lesion size was measured histologically after euthanization. RESULTS The mean depth of 30, 100, and 300 J lesions was 3.2 ± 0.7, 6.3 ± 1.8, and 8.0 ± 1.5 mm, respectively (P = .0003). The mean width of 30, 100, and 300 J lesions was 10.1 ± 0.8, 15.1 ± 1.5, and 17.1 ± 1.3 mm, respectively (P<.0001). Significant tissue shrinkage was observed at the higher energy levels. No luminal arterial narrowing was observed after 3 months: 2.3 ± 0.3 mm vs 2.3 ± 0.4 mm (P = .85). CONCLUSION The relationship between the amount of electroporation energy delivered through a linear suction device with a single linear electrode and the mean myocardial lesion size is significant in the absence of major adverse events or permanent damage to the coronary arteries.

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.

Novel method for electrode-tissue contact measurement with multi-electrode catheters

Aims With multi-electrode catheters, measuring contact force (CF) on each electrode is technically challenging. Present electrical methods, like the electrical coupling index (ECI) may yield false positive values in pulmonary veins. We developed a novel method that measures electrode-interface resistance (IR) by applying a very local electrical field between neighbouring catheter electrodes while measuring voltage between each catheter electrode and a skin patch. The aim of this study was to evaluate the new IR method to measure electrode-tissue contact. Methods and results In vitro, effects of remote high-impedance structures were studied. In addition, both ECI and IR were directly compared with true electrode-tissue CF. In five pigs, the influence of high-impedance pulmonary tissue on ECI and IR was investigated while navigating the free floating catheter into the caval veins. Inside the left atrium (LA), IR was directly compared with CF. Finally, multi-electrode IR measurements in the LA and inferior pulmonary vein (IPV) were compared. In vitro, IR is much less affected by remote high-impedance structures than ECI (3% vs. 32%). Both IR and ECI strongly relate to electrode-tissue CF (r2 = 0.84). In vivo, and in contrast to ECI, IR was not affected by nearby pulmonary tissue. Inside the LA, a strong relation between IR and CF was found. This finding was confirmed by simultaneous multi-electrode measurements in LA and IPV. Conclusion Data of the present study suggest that electrode-tissue contact affects the IR while being highly insensitive to remote structures. This method facilitates electrode-tissue contact measurements with circular multi-electrode ablation catheters.

3D Hybrid Imaging for Structural and Congenital Heart Interventions in the Cath Lab

ABSTRACT Hybrid imaging (HI) during cardiovascular interventions enables the peri-procedural visualization of the organs and tissues by means of integrating different imaging modalities. HI can improve the procedural efficacy and safety. This review provides an overview of different systems, their possibilities and the current clinical use and benefits focused on structural and congenital heart diseases. We have performed a literature search and linked the software options to the clinical use in cardiology to gain insight into the clinical use of the systems. In this review, we focus on radiation and contrast exposure, complication rate and procedure time. We found that currently available studies are limited by small cohorts. Nevertheless, HI systems for valvular procedures result in a significant decrease of radiation and contrast exposure. The largest benefit hereof is observed when HI is used in combination with rotational angiography. Furthermore, automatically determined optimal implant angle for transcatheter aortic valve implantation decreases the complication rate significantly. Congenital heart disease interventions that require 2D/3D Transoesophageal echocardiography (TEE) such as septal defects show a significant decrease in radiation and contrast exposure and procedural time when using TEE-Mono- and bi-plane cine angiography and fluoroscopy (XRF) fusion software. MitraClip procedures using these HI systems, however, show only a trend in decrease of these effects. In conclusion, major interventional X-ray vendors offer HI software solutions which are safe and can aid the planning and image guidance of cardiovascular interventions. Even though current HI technologies have limitations, HI provides support in the increasingly complex cardiac interventional procedures to provide better patient care.

3D Whole-heart Myocardial Tissue Analysis

Cardiac regenerative therapies aim to protect and repair the injured heart in patients with ischemic heart disease. By injecting stem cells or other biologicals that enhance angio- or vasculogenesis into the infarct border zone (IBZ), tissue perfusion is improved, and the myocardium can be protected from further damage. For maximum therapeutic effect, it is hypothesized that the regenerative substance is best delivered to the IBZ. This requires accurate injections and has led to the development of new injection techniques. To validate these new techniques, we have designed a validation protocol based on myocardial tissue analysis. This protocol includes whole-heart myocardial tissue processing that enables detailed two-dimensional (2D) and three-dimensional (3D) analysis of the cardiac anatomy and intramyocardial injections. In a pig, myocardial infarction was created by a 90-min occlusion of the left anterior descending coronary artery. Four weeks later, a mixture of a hydrogel with superparamagnetic iron oxide particles (SPIOs) and fluorescent beads was injected in the IBZ using a minimally-invasive endocardial approach. 1 h after the injection procedure, the pig was euthanized, and the heart was excised and embedded in agarose (agar). After the solidification of the agar, magnetic resonance imaging (MRI), slicing of the heart, and fluorescence imaging were performed. After image post-processing, 3D analysis was performed to assess the IBZ targeting accuracy. This protocol provides a structured and reproducible method for the assessment of the targeting accuracy of intramyocardial injections into the IBZ. The protocol can be easily used when the processing of scar tissue and/or validation of the injection accuracy of the whole heart is desired.