Interventional cardiac magnetic resonance imaging: current applications, technology readiness level, and future perspectives.

BACKGROUND: Cardiac magnetic resonance (CMR) provides excellent temporal and spatial resolution, tissue characterization, and flow measurements. This enables major advantages when guiding cardiac invasive procedures compared with X-ray fluoroscopy or ultrasound guidance. However, clinical implementation is limited due to limited availability of technological advancements in magnetic resonance imaging (MRI) compatible equipment. A systematic review of the available literature on past and present applications of interventional MR and its technology readiness level (TRL) was performed, also suggesting future applications. METHODS: A structured literature search was performed using PubMed. Search terms were focused on interventional CMR, cardiac catheterization, and other cardiac invasive procedures. All search results were screened for relevance by language, title, and abstract. TRL was adjusted for use in this article, level 1 being in a hypothetical stage and level 9 being widespread clinical translation. The papers were categorized by the type of procedure and the TRL was estimated. RESULTS: Of 466 papers, 117 papers met the inclusion criteria. TRL was most frequently estimated at level 5 meaning only applicable to in vivo animal studies. Diagnostic right heart catheterization and cavotricuspid isthmus ablation had the highest TRL of 8, meaning proven feasibility and efficacy in a series of humans. CONCLUSION: This article shows that interventional CMR has a potential widespread application although clinical translation is at a modest level with TRL usually at 5. Future development should be directed toward availability of MR-compatible equipment and further improvement of the CMR techniques. This could lead to increased TRL of interventional CMR providing better treatment.

Multielectrode Contact Measurement Can Improve Long-Term Outcome of Pulmonary Vein Isolation Using Circular Single-Pulse Electroporation Ablation.

BACKGROUND: Irreversible electroporation (IRE) ablation is generally performed with multielectrode catheters. Electrode-tissue contact is an important predictor for the success of pulmonary vein (PV) isolation; however, contact force is difficult to measure with multielectrode ablation catheters. In a preclinical study, we assessed the feasibility of a multielectrode impedance system (MEIS) as a predictor of long-term success of PV isolation. In addition, we present the first-in-human clinical experience with MEIS. METHODS: In 10 pigs, one PV was ablated based on impedance (MEIS group), and the other PV was solely based on local electrogram information (EP group). IRE ablations were performed at 200 J. After 3 months, recurrence of conduction was assessed. Subsequently, in 30 patients undergoing PV isolation with IRE, MEIS was evaluated and MEIS contact values were compared to local electrograms. RESULTS: In the porcine study, 43 IRE applications were delivered in 19 PVs. Acutely, no reconnections were observed in either group. After 3 months, 0 versus 3 (P=0.21) PVs showed conduction recurrence in the MEIS and EP groups, respectively. Results from the clinical study showed a significant linear relation was found between mean MEIS value and bipolar dV/dt (r2=0.49, P<0.001), with a slope of 20.6 mV/s per Ohm. CONCLUSIONS: Data from the animal study suggest that MEIS values predict effective IRE applications. For the long-term success of electrical PV isolation with circular IRE applications, no significant difference in efficacy was found between ablation based on the measurement of electrode interface impedance and ablation using the classical EP approach for determining electrode-tissue contact. Experiences of the first clinical use of MEIS were promising and serve as an important basis for future research.

Characteristics and time course of acute and chronic myocardial lesion formation after electroporation ablation in the porcine model.

INTRODUCTION: Electroporation ablation creates deep and wide myocardial lesions. No data are available on time course and characteristics of acute lesion formation. METHODS: For the acute phase of myocardial lesion development, seven pigs were investigated. Single 200 J applications were delivered at four different epicardial right ventricular sites using a linear suction device, yielding a total of 28 lesions. Timing of applications was designed to yield lesions at seven time points: 0, 10, 20, 30, 40, 50, and 60 min, with four lesions per time point. After killing, lesion characteristics were histologically investigated. For the chronic phase of myocardial lesion development, tissue samples were used from previously conducted studies where tissue was obtained at 3 weeks and 3 months after electroporation ablation. RESULTS: Acute myocardial lesions induce a necrosis pattern with contraction band necrosis and interstitial edema, immediately present after electroporation ablation. No further histological changes such as hemorrhage or influx of inflammatory cells occurred in the first hour. After 3 weeks, the lesions consisted of sharply demarcated loose connective tissue that further developed to more fibrotic scar tissue after 3 months without additional changes. Within the scar tissue, arteries and nerves were unaffected. CONCLUSION: Electroporation ablation immediately induces contraction band necrosis and edema without additional tissue changes in the first hour. After 3 weeks, a sharply demarked scar has been developed that remains stable during follow-up of 3 months. This is highly relevant for clinical application of electroporation ablation in terms of the electrophysiological endpoint and waiting period after ablation.

Persistent phrenic nerve palsy after atrial fibrillation ablation: Follow-up data from The Netherlands Heart Registration.

BACKGROUND: Persistent phrenic nerve palsy (PNP) is an established complication of atrial fibrillation (AF) ablation, especially during cryoballoon and thoracoscopic ablation. Data on persistent PNP reversibility is limited because most patients recover <24 h. This study aims to investigate persistent PNP recovery, freedom of PNP-related symptoms after AF ablation and identify baseline variables associated with the occurrence and early PNP recovery in a large nationwide registry study. METHODS: In this study, we used data from the Netherlands Heart Registration, comprising data from 9549 catheter and thoracoscopic AF ablations performed in 2016 and 2017. PNP data was available of 7433 procedures, and additional follow-up data were collected for patients who developed persistent PNP. RESULTS: Overall, the mean age was 62 ± 10 years, and 67.7% were male. Fifty-four (0.7%) patients developed persistent PNP and follow-up was available in 44 (81.5%) patients. PNP incidence was 0.07%, 0.29%, 1.41%, and 1.25%, respectively for patients treated with conventional-RF, phased-RF, cryoballoon, and thoracoscopic ablation respectively. Seventy-one percent of the patients fully recovered, and 86% were free of PNP-related symptoms after a median follow-up of 203 (113-351) and 184 (82-359) days, respectively. Female sex, cryoballoon, and thoracoscopic ablation were associated with a higher risk to develop PNP. Patients with PNP recovering ≤180 days had a larger left atrium volume index than those with late or no recovery. CONCLUSION: After AF ablation, persistent PNP recovers in the majority of patients, and most are free of symptoms. Female patients and patients treated with cryoballoon or thoracoscopic ablation are more prone to develop PNP.

High-frequency irreversible electroporation for cardiac ablation using an asymmetrical waveform.

BACKGROUND: Irreversible electroporation (IRE) using direct current (DC) is an effective method for the ablation of cardiac tissue. A major drawback of the use of DC-IRE, however, are two problems: requirement of general anesthesia due to severe muscle contractions and the formation of bubbles containing gaseous products from electrolysis. The use of high-frequency alternating current (HF-IRE) is expected to solve both problems, because HF-IRE produces little to no muscle spasms and does not cause electrolysis. METHODS: In the present study, we introduce a novel asymmetric, high-frequency (aHF) waveform for HF-IRE and present the results of a first, small, animal study to test its efficacy. RESULTS: The data of the experiments suggest that the aHF waveform creates significantly deeper lesions than a symmetric HF waveform of the same energy and frequency (p = 0.003). CONCLUSION: We therefore conclude that the use of the aHF enhances the feasibility of the HF-IRE method.

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.

Five-year efficacy of pulmonary vein antrum isolation as a primary ablation strategy for atrial fibrillation: a single-centre cohort study.

AIMS: Pulmonary vein antrum isolation (PVAI) is the cornerstone of atrial fibrillation (AF) ablation. There is an ongoing discussion on whether and when to add substrate modification to PVAI. This study evaluates (1) long-term efficacy of PVAI as a primary ablation strategy in all patients independently from AF type and (2) predictors of arrhythmia recurrence. METHODS AND RESULTS: A total of 509 consecutive patients (mean age 57 years, 38.9% non-paroxysmal AF) with AF underwent PVAI. In redo procedures, ablation was restricted to re-pulmonary vein (PV) isolation in case of PV reconnection. If the PVs were found to be isolated, substrate modification was performed. In total, 774 procedures were performed. Mean follow-up duration after the first and last ablation was, respectively, 66 ± 23 and 55 ± 25 months. A single PVAI was sufficient in restoring and maintaining long-term sinus rhythm in 41.3% (n = 210) of patients. Multiple procedures (mean 1.5) with re-PV isolation increased long-term success to 58.3% (n = 297). Additional substrate modification (n = 70) increased success to 62.5% (n = 318). After the last ablation, 87.5% of patients experienced success or significant clinical improvement on or off antiarrhythmic drugs. The incidence of left-sided atrial flutter or atrial tachycardia was 5% after PVAI and increased to 32% after additional substrate modification. Independent predictors for arrhythmia recurrence after the last ablation were non-paroxysmal AF, female sex, body mass index, hypertension, and AF duration. CONCLUSION: Five-year freedom of atrial tachyarrhythmia could be achieved by PVAI as primary ablation strategy in 58.3% of patients. Additional substrate modification only moderately increased overall success.

Non-invasive focus localization, right ventricular epicardial potential mapping in patients with an MRI-conditional pacemaker system - a pilot study.

BACKGROUND: With the advent of magnetic resonance imaging (MRI) conditional pacemaker systems, the possibility of performing MRI in pacemaker patients has been introduced. Besides for the detailed evaluation of atrial and ventricular volumes and function, MRI can be used in combination with body surface potential mapping (BSPM) in a non-invasive inverse potential mapping (IPM) strategy. In non-invasive IPM, epicardial potentials are reconstructed from recorded body surface potentials (BSP). In order to investigate whether an IPM method with a limited number of electrodes could be used for the purpose of non-invasive focus localization, it was applied in patients with implanted pacing devices. Ventricular paced beats were used to simulate ventricular ectopic foci. METHODS: Ten patients with an MRI-conditional pacemaker system and a structurally normal heart were studied. Patient-specific 3D thorax volume models were reconstructed from the MRI images. BSP were recorded during ventricular pacing. Epicardial potentials were inversely calculated from the BSP. The site of epicardial breakthrough was compared to the position of the ventricular lead tip on MRI and the distance between these points was determined. RESULTS: For all patients, the site of earliest epicardial depolarization could be identified. When the tip of the pacing lead was implanted in vicinity to the epicardium, i.e. right ventricular (RV) apex or RV outflow tract, the distance between lead tip position and epicardial breakthrough was 6.0 ± 1.9 mm. CONCLUSIONS: In conclusion, the combined MRI and IPM method is clinically applicable and can identify sites of earliest depolarization with a clinically useful accuracy.

Low vulnerability of the right phrenic nerve to electroporation ablation.

BACKGROUND: Circular electroporation ablation is a novel ablation modality for electrical pulmonary vein isolation. With a single 200-J application, deep circular myocardial lesions can be created. However, the acute and chronic effects of this energy source on phrenic nerve (PN) function are unknown. OBJECTIVE: The purpose of this study was to analyze nerve vulnerability to electroporation ablation in a porcine model. METHODS: In 20 animals (60-75 kg), the course of the right PN was pace-mapped inside the superior caval vein (SCV). Thereafter, a single 200-J circular electroporation ablation was performed via a multipolar circular catheter in firm contact with the inner SCV wall. RESULTS: In 19 of 20 animals, the PN could be captured along an estimated 6-8 cm trajectory above the right atrial contour. Directly after the application, the PN could be captured above the ablation level in 17 of 19 animals and after maximally 30 minutes in all animals. Fifteen animals were restudied after 3-13 weeks, and PN functionality was unaffected in all. Histological analysis in 5 animals in which the application had been delivered in the muscular sleeve just above the right atrium showed a transmural circular lesion. However, no lesion was found in the other animals in which the application had been delivered in the fibrous section more cranial in the SCV. CONCLUSIONS: Electroporation ablation at an energy level that may create deep myocardial lesions may spare the targeted right PN. These animal data suggest that electroporation may be a safe ablation modality near the right PN.

Computing volume potentials for noninvasive imaging of cardiac excitation.

BACKGROUND: In noninvasive imaging of cardiac excitation, the use of body surface potentials (BSP) rather than body volume potentials (BVP) has been favored due to enhanced computational efficiency and reduced modeling effort. Nowadays, increased computational power and the availability of open source software enable the calculation of BVP for clinical purposes. In order to illustrate the possible advantages of this approach, the explanatory power of BVP is investigated using a rectangular tank filled with an electrolytic conductor and a patient specific three dimensional model. METHODS: MRI images of the tank and of a patient were obtained in three orthogonal directions using a turbo spin echo MRI sequence. MRI images were segmented in three dimensional using custom written software. Gmsh software was used for mesh generation. BVP were computed using a transfer matrix and FEniCS software. RESULTS: The solution for 240,000 nodes, corresponding to a resolution of 5 mm throughout the thorax volume, was computed in 3 minutes. The tank experiment revealed that an increased electrode surface renders the position of the 4 V equipotential plane insensitive to mesh cell size and reduces simulated deviations. In the patient-specific model, the impact of assigning a different conductivity to lung tissue on the distribution of volume potentials could be visualized. CONCLUSION: Generation of high quality volume meshes and computation of BVP with a resolution of 5 mm is feasible using generally available software and hardware. Estimation of BVP may lead to an improved understanding of the genesis of BSP and sources of local inaccuracies.

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.

Noninvasive imaging of cardiac excitation: current status and future perspective.

Noninvasive imaging of cardiac excitation using body surface potential mapping (BSPM) data and inverse procedures is an emerging technique that enables estimation of myocardial depolarization and repolarization. Despite numerous reports on the possible advantages of this imaging technique, it has not yet advanced into daily clinical practice. This is mainly due to the time consuming nature of data acquisition and the complexity of the mathematics underlying the used inverse procedures. However, the popularity of this field of research has increased and noninvasive imaging of cardiac electrophysiology is considered a promising tool to complement conventional invasive electrophysiological studies. Furthermore, the use of appropriately designed electrode vests and more advanced computers has greatly reduced the procedural time. This review provides descriptive overview of the research performed thus far and the possible future directions. The general challenges in routine application of BSPM and inverse procedures are discussed. In addition, individual properties of the biophysical models underlying the inverse procedures are illustrated.