Local impedance-guided radiofrequency ablation with standard and high power: Results of a preclinical investigation.

BACKGROUND: Local impedance (LI) drop measured with microfidelity electrodes embedded in the tip of an ablation catheter accurately reflects tissue heating during radiofrequency (RF) ablation. Previous studies found 15-30 Ω LI drops created successful lesions, while more than 40 Ω drops were associated with steam pops. The objective of this study was to evaluate the safety and efficacy of LI-guided ablation using standard (30 W) and high-power (50 W) in a preclinical model. METHODS: RF lesions were created in explanted swine hearts (n = 6) to assess the feasibility of LI-guided ablation by targeting 10, 20, or 30 Ω (n = 20/group) drops. Subsequently, LI-guided ablation was evaluated in a chronic animal model (n = 8 Canines, 25-29 kg, 30/50 W). During the index procedure point-by-point intercaval line ablation and left inferior pulmonary vein (PV) isolation were performed. RF duration was at the operators' discretion but discontinued early if a 15-30 Ω drop was achieved. Operators attempted to avoid LI drops of more than 40 Ω. At 1-month, durable conduction block was evaluated with electroanatomic mapping followed by necropsy and histopathology. RESULTS: In explanted tissue, terminating ablation at 10, 20, or 30 Ω LI drops created statistically larger lesions (p < .05; 1.8 [1.6-2.4] mm, 3.3 [3.0-3.7] mm; 4.9 [4.3-5.5] mm). LI-guided high-power ablation in vivo significantly reduced RF duration per application compared to standard-power (p < .05; intercaval: 8.9 ± 5.2 vs. 18.1 ± 11.0 s, PV: 9.6 ± 5.4 vs. 23.2 ± 10.3 s). LI drops of 15-40 Ω were more readily achievable for high-power (90.1%, 318/353) than standard-power (71.7%, 243/339). All intercaval lines and PV isolations were durable (16/16) at 1-month. Necropsy revealed no major collateral injury to the pericardium, phrenic nerve, esophagus, or lungs. There was no pericardial effusion, stroke, tamponade, or PV stenosis. Vagal nerve injury was found in two 30 W animals after using 19.7 ± 13.9 and 19.5 ± 11.8 s RF applications. CONCLUSION: LI-guided ablation was found to be safe and efficacious in a chronic animal model. High-power ablation more readily achieved more than 15 Ω drops, reduced RF duration compared with standard-power, and had no major RF collateral injury.

Long-term performance of a novel communicating antitachycardia pacing-enabled leadless pacemaker and subcutaneous implantable cardioverter-defibrillator system: A comprehensive preclinical study.

BACKGROUND: Subcutaneous implantable cardioverter-defibrillators (S-ICDs) and leadless pacemakers (LPs) are intended to diminish transvenous lead-related complications. However, S-ICDs do not deliver antibradycardia pacing or antitachycardia pacing, and currently, there is no commercially available coordinated leadless option for patients with defibrillator and (expected) pacing needs. OBJECTIVE: We evaluated the performance, safety, and potential replacement strategies of a novel modular cardiac rhythm management (mCRM) system, a wirelessly communicating antitachycardia pacing-enabled LP and S-ICD in a preclinical model. METHODS: LP implantation was attempted in 68 canine subjects, and in 38 an S-ICD was implanted as well. Animals were evaluated serially up to 18 months. At all evaluations, communication thresholds (CTs) between the devices, LP electrical parameters, and system-related complications were assessed. Different replacement strategies were tested. RESULTS: The LP was successfully implanted in 67 of 68 (98.5%) and the concomitant S-ICD in 38 of 38 (100%). mCRM communication was successful in 1022 of 1024 evaluations (99.8%). The mean CT was 2.2 ± 0.7 V at implantation and stable afterward (18 months: 1.8 ± 0.7 V). In multivariable analysis, larger LP-to-S-ICD angle and dorsal posture were associated with higher CTs. At implantation, the mean pacing capture threshold, impedance, and R-wave amplitude were 0.3 ± 0.1 V, 898.4 ± 198.9 Ω, and 26.4 ± 8.2 mV. The mean pacing capture threshold remained stable and impedance and R-wave amplitudes were within acceptable ranges throughout (0.7 ± 0.4 V, 619.1 ± 90.6 Ω, and 20.1 ± 8.4 mV at 18 months). Different replacement strategies seem feasible. CONCLUSION: This first mCRM system demonstrated excellent performance up to 18 months in a preclinical model.

Improved Ablation Efficiency in PVI Guided by Contact Force and Local Impedance: Chronic Canine Model.

Background: The purpose of this study was to assess the effect local impedance (LI) has on an ablation workflow when combined with a contact force (CF) ablation catheter. Methods: Left pulmonary vein isolation was performed in an in vivo canine model (N = 8) using a nominal (30 W) or an elevated (50 W) power strategy with a CF catheter. The catheter was enabled to measure LI prior to and during ablation. LI was visible for only one of the vein isolations. Results: Chronic block was achieved in all animals when assessed 30 ± 5 days post-ablation procedure with a median LI drop during RF ranging from 23.0 to 34.0 Ω. In both power cohorts, the median radiofrequency (RF) duration decreased if LI was visible to the operator (30 W only CF: 17.0 s; 30 W CF + LI: 14.0 s, p = 0.009; 50 W only CF: 6.0 s; 50 W CF + LI: 4.0 s, p = 0.019). An inverse relationship between the LI prior to RF delivery and the RF duration required to achieve an effective lesion was observed. There was no correlation between the magnitude of the applied force and the drop in LI, once at least 5 g was achieved. Conclusions: An elevated power strategy with the context of CF and LI led to the most efficient titration of successful RF energy delivery. The combination of feedback allows for customization of the ablation strategy based on local tissue variation rather than a uniform approach that could potentially lead to overtreatment. Higher LI drops were more readily achievable when an elevated power strategy was utilized, especially in conditions where the catheter was coupled against tissue with low resistivity. Clinical study is warranted to determine if there is an additive safety benefit to visualizing the dynamics of the tissue response to RF energy with LI when an elevated power strategy is used.

Time-Averaged Wavefront Analysis Demonstrates Preferential Pathways of Atrial Fibrillation, Predicting Pulmonary Vein Isolation Acute Response.

Electrical activation during atrial fibrillation (AF) appears chaotic and disorganised, which impedes characterisation of the underlying substrate and treatment planning. While globally chaotic, there may be local preferential activation pathways that represent potential ablation targets. This study aimed to identify preferential activation pathways during AF and predict the acute ablation response when these are targeted by pulmonary vein isolation (PVI). In patients with persistent AF (n = 14), simultaneous biatrial contact mapping with basket catheters was performed pre-ablation and following each ablation strategy (PVI, roof, and mitral lines). Unipolar wavefront activation directions were averaged over 10 s to identify preferential activation pathways. Clinical cases were classified as responders or non-responders to PVI during the procedure. Clinical data were augmented with a virtual cohort of 100 models. In AF pre-ablation, pathways originated from the pulmonary vein (PV) antra in PVI responders (7/7) but not in PVI non-responders (6/6). We proposed a novel index that measured activation waves from the PV antra into the atrial body. This index was significantly higher in PVI responders than non-responders (clinical: 16.3 vs. 3.7%, p = 0.04; simulated: 21.1 vs. 14.1%, p = 0.02). Overall, this novel technique and proof of concept study demonstrated that preferential activation pathways exist during AF. Targeting patient-specific activation pathways that flowed from the PV antra to the left atrial body using PVI resulted in AF termination during the procedure. These PV activation flow pathways may correspond to the presence of drivers in the PV regions.

Combined local impedance and contact force for radiofrequency ablation assessment.

BACKGROUND: The combination of contact force (CF) and local impedance (LI) may improve tissue characterization and lesion prediction during radiofrequency (RF) ablation. OBJECTIVE: The purpose of this study was to evaluate the utility of LI combined with CF in assessing RF ablation efficacy. METHODS: An LI catheter with CF sensing was evaluated in swine (n = 11) and in vitro (n = 14). The relationship between LI and CF in different tissue types was evaluated in vivo. Discrete lesions were created in vitro and in vivo at a range of forces, powers, and durations. Finally, an intercaval line was created in 3 groups at 30 W: 30s, Δ20Ω, and Δ30Ω. In the Δ20Ω and Δ30Ω groups, the user ablated until a 20 or 30 Ω LI drop. In the 30s group, the user was blinded to LI. RESULTS: In vivo, distinction in LI was found between the blood pool and the myocardium (blood pool: 122 ± 7.02 Ω; perpendicular contact: 220 ± 29 Ω; parallel contact: 207 ± 31 Ω). LI drop correlated with lesion depth both in vitro (R = 0.84) and in vivo (R = 0.79), informing sufficient lesion creation (LI drop >20 Ω) and warning of excessive heating (LI drop >65 Ω). When creating an intercaval line, the total RF time was significantly reduced when using LI guidance (6.4 ± 2 minutes in Δ20Ω and 8.1 ± 1 minutes in Δ30Ω) compared with a standard 30-second workflow (18 ± 7 minutes). Acute conduction block was achieved in all Δ30Ω and 30s lines. CONCLUSION: The addition of LI to CF provides feedback on both electrical and mechanical loads. This provides information on tissue type and catheter-tissue coupling; provides feedback on whether volumetric tissue heating is inadequate, sufficient, or excessive; and reduces ablation time.

Ventricular preexcitation modulates strain and attenuates cardiac remodeling in a swine model of myocardial infarction.

BACKGROUND: Myocardial infarction modifies the distribution of stress within the heart, increasing wall stress in ischemic and surrounding tissue, which often leads to adverse left ventricular remodeling. Electrical preexcitation pacing with appropriate timing of high-stress regions can reduce local strain and may attenuate global remodeling. METHODS AND RESULTS: Myocardial infarction was induced in 24 swine to study the short-term (n=12) and long-term (n=12) effects of therapy. Sonomicrometry and hemodynamic measurements were used to show the mechanistic effects of preexcitation and to determine the optimal stimulation site and atrioventricular delay. Lagrangian strain was used to assess regional loading characteristics. Long-term study animals were randomized to 8 weeks of preexcitation (therapy) or no pacing (control). Echocardiograms were performed 2 days after myocardial infarction and repeated at 60 days, when tissue weights and apoptosis were assessed. Preexcitation reduced regional strain in the short term, with the best results achieved when the border region was paced at an atrioventricular delay of 50% of the intrinsic PR interval. In the long term, the changes in left ventricular internal diameter and left atrial size were decreased in therapy animals versus control animals (0.9+/-0.3 versus 1.5+/-0.5 cm, P=0.03, and 1.06+/-0.78 versus 2.32+/-0.88 cm, P<0.04, respectively). Heart weight was significantly lower in the therapy animals than in the control animals (319.8+/-20.8 versus 359.6+/-29.3 g, P=0.02). Although not significant, cardiomyocyte apoptosis trended lower in the therapy group. CONCLUSIONS: Preexcitation of the left ventricle after myocardial infarction reduced strain and stroke work in the infarct and border regions in the short term and attenuated adverse ventricular remodeling in the long term.

Novel Measure of Local Impedance Predicts Catheter-Tissue Contact and Lesion Formation.

BACKGROUND: Coupling between the ablation catheter and myocardium is critical to resistively heat tissue with radiofrequency ablation. The objective of this study was to evaluate whether a novel local impedance (LI) measurement on an ablation catheter identifies catheter-tissue coupling and is predictive of lesion formation. METHODS AND RESULTS: LI was studied in explanted hearts (n=10 swine) and in vivo (n=10; 50-70 kg swine) using an investigational electroanatomic mapping system that measures impedance from an ablation catheter with mini-electrodes incorporated in the distal electrode (Rhythmia and IntellaNav MiFi OI, Boston Scientific). Explanted tissue was placed in a warmed (37 °C) saline bath mounted on a scale, and LI was measured 15 mm away from tissue to 5 mm of catheter-tissue compression at multiple catheter angles. Lesions were created with 31 and 50 W for 5 to 45 seconds (n=90). During in vivo evaluation of LI, measurements of myocardium (n=90) and blood pool (n=30) were guided by intracardiac ultrasound while operators were blinded to LI data. Lesions were created with 31 and 50 W for 45 seconds in the ventricles (n=72). LI of myocardium (119.7 Ω) was significantly greater than that of blood pool (67.6 Ω; P<0.01). Models that incorporate LI drop (ΔLI) to predict lesion size had better performance than models that incorporate force-time integral (R2=0.75 versus R2=0.54) and generator impedance drop (R2=0.82 versus R2=0.58). Steam pops displayed a significantly higher starting LI and larger ΔLI compared with successful radiofrequency applications (P<0.01). CONCLUSIONS: LI recorded from miniature electrodes provides a valuable measure of catheter-tissue coupling, and ΔLI is predictive of lesion formation during radiofrequency ablation.

Unraveling the Underlying Arrhythmia Mechanism in Persistent Atrial Fibrillation: Results From the STARLIGHT Study.

BACKGROUND: The mechanisms that initiate and sustain persistent atrial fibrillation are not well characterized. Ablation results remain significantly worse than in paroxysmal atrial fibrillation in which the mechanism is better understood and subsequent targeted therapy has been developed. The aim of this study was to characterize and quantify patterns of activation during atrial fibrillation using contact mapping. METHODS: Patients with persistent atrial fibrillation (n=14; mean age, 61±8 years; ejection fraction, 59±10%) underwent simultaneous biatrial contact mapping with 64 electrode catheters. The atrial electrograms were transformed into phase, and subsequent spatiotemporal mapping was performed to identify phase singularities (PSs). RESULTS: PSs were located in both atria, but we observed more PSs in the left atrium compared with the right atrium (779±302, 552±235; P=0.015). Although some PSs of duration sufficient to complete >1 rotation were detected, the maximum PS duration was only 1150 ms, and the vast majority (97%) of PSs persisted for too short a period to complete a full rotation. Although in selected patients there was evidence of PS local clustering, overall, PSs were distributed globally throughout both chambers with no clear anatomic predisposition. In a subset of patients (n=7), analysis was repeated using an alternative established atrial PS mapping technique, which confirmed our initial findings. CONCLUSIONS: No sustained rotors or localized drivers were detected, and instead, the mechanism of arrhythmia maintenance was consistent with the multiple wavelet hypothesis, with passive activation of short-lived rotational activity. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01765075.

Acute and 3-Month Performance of a Communicating Leadless Antitachycardia Pacemaker and Subcutaneous Implantable Defibrillator.

OBJECTIVES: The primary objective was to assess the acute and 3-month performance of the modular antitachycardia pacing (ATP)-enabled leadless pacemaker (LP) and subcutaneous implantable cardioverter-defibrillator (S-ICD) system, particularly device-device communication and ATP delivery. BACKGROUND: Transvenous pacemakers and implantable cardioverter-defibrillators (ICDs) have considerable rates of lead complications. We examined the next step in multicomponent leadless cardiac rhythm management: feasibility of pacing (including ATP) by a LP, commanded by an implanted S-ICD through wireless, intrabody, device-device communication. METHODS: The combined modular cardiac rhythm management therapy system of the LP and S-ICD prototypes was evaluated in 3 animal models (ovine, porcine, and canine) both in acute and chronic (90 days) experiments. LP performance, S-ICD to LP communication, S-ICD and LP rhythm discrimination, and ATP delivery triggered by the S-ICD were tested. RESULTS: The LP and S-ICD were successfully implanted in 98% of the animals (39 of 40). Of the 39 animals, 23 were followed up for 90 days post-implant. LP performance was adequate and exhibited appropriate VVI behavior during the 90 days of follow-up in all tested animals. Unidirectional communication between the S-ICD and LP was successful in 99% (398 of 401) of attempts, resulting in 100% ATP delivery by the LP (10 beats at 81% of the coupling interval). Adequate S-ICD sensing was observed during normal sinus rhythm, LP pacing, and ventricular tachycardia/ventricular fibrillation. CONCLUSIONS: This study presents the preclinical acute and chronic performance of the combined function of an ATP-enabled LP and S-ICD. Appropriate VVI functionality, successful wireless device-device communication, and ATP delivery were demonstrated by the LP. Clinical studies on safety and performance are needed.

Practical Considerations of Mapping Persistent Atrial Fibrillation With Whole-Chamber Basket Catheters.

OBJECTIVES: This study sought to evaluate basket catheter deployment, catheter-tissue contact, and time-space stability of unipolar atrial electrograms (aEGMs) recorded in persistent atrial fibrillation (AF) patients. BACKGROUND: Panoramic mapping of human AF using multiple-electrode basket catheters may identify AF sources. Although clinical results using this technique are provocative, questions remain about its effectiveness. METHODS: Data were collected from patients (N = 25) undergoing catheter ablation for AF during the multicenter STARLIGHT (Signal Transfer of Atrial Fibrillation Data to Guide Human Treatment) trial (NCT01765075). Left and right aEGM signals were recorded using basket catheters during baseline AF, following ablation and during sinus rhythm. Data were analyzed for basket deployment, peak-to-peak voltage, and electrogram stability and organization. Electrogram stability and organization were evaluated via time-frequency analysis (TFA). RESULTS: Basket catheters displayed equatorial bunching when deployed in atria. Interspline spacing ranged from 1.7 to 64.0 mm in the right atrial and from 1.5 to 85.08 mm in the left atrial basket. Approximately one-third of mapping electrodes failed to demonstrate a median peak-to-peak voltage >2× the low-voltage threshold. Time-space stability and organization was observed in 13 of 22 (59.09%) right atrial and 10 of 22 (45.45%) left atrial baskets. CONCLUSIONS: Despite poor deployment and a large number of low-voltage electrodes, stability and organization was observed in about one-half of the mapped patients. Although this study suggests that basket catheters have limitations for patient-specific AF mapping, concordant activation occurs in some persistent AF patients, which may be amenable to high-density mapping techniques.

Long-term caspase inhibition ameliorates apoptosis, reduces myocardial troponin-I cleavage, protects left ventricular function, and attenuates remodeling in rats with myocardial infarction.

OBJECTIVES: This study was designed to evaluate whether in vivo caspase inhibition can prevent myocardial contractile protein degradation, improve myocardial function, and attenuate ventricular remodeling. BACKGROUND: Apoptosis is thought to play an important role in the development and progression of heart failure (HF) after a myocardial infarction (MI). However, it is not known whether inhibiting apoptosis can attenuate left ventricular (LV) remodeling and minimize systolic dysfunction. METHOD: A 28-day infusion of caspase inhibitor (n = 12) or vehicle (n = 9) was administered to rats immediately after an anterior MI. In addition, five sham-operated rats given the caspase inhibitor were compared with 17 untreated sham-operated animals to study effects in non-MI rats. Left ventricular function, remodeling parameters, and hemodynamics were studied four weeks later. Myocardial caspase 3 activation and troponin-I contractile protein cleavage were studied in the non-infarct, remote LV myocardium using Western blots. Apoptosis was assessed using immunohistochemistry for activated caspase-positive cells as well as the TUNEL method. Collagen volume was estimated using morphometry. RESULTS: Caspase inhibition reduced myocardial caspase 3 activation. This was accompanied by less cleavage of troponin-I, an important component of the cardiac contractile apparatus, and fewer apoptotic cardiomyocytes. Furthermore, caspase inhibition reduced LV-weight-to-body-weight ratio, decreased myocardial interstitial collagen deposition, attenuated LV remodeling, and better preserved LV systolic function after MI. CONCLUSIONS: Caspase inhibition, started soon after MI and continued for four weeks, preserves myocardial contractile proteins, reduces systolic dysfunction, and attenuates ventricular remodeling. These findings may have important therapeutic implications in post-MI HF.