Optimal conditions for high-power, short-duration radiofrequency ablation using a novel, flexible-tipped, force-sensing catheter.

Background: High-power, short-duration (HPSD) radiofrequency ablation (RFA) reduces procedure time; however, safety and efficacy thresholds vary with catheter design. Objective: The study sought to determine optimal HPSD ablation conditions with a novel flexible-tipped, contact force-sensing RFA catheter. Methods: RFA lesions were created in thigh muscle (16 swine) over a range of conditions (51-82 W, 2-40 g, 8-40 mL/min irrigation). An intracardiac study was performed (12 swine) to characterize steam pop thresholds. Lesions were created in a second intracardiac study (14 swine, n = 290 pulmonary vein isolation [PVI] lesions) with combinations of radiofrequency power, duration, and contact force. PVI was tested, animals were sacrificed, and lesions were measured. Results: The likelihood of coagulation formation in the thigh model was <20% when power was ≤79 W, when contact force was ≤40 g, when duration was ≤11 seconds, and when irrigation rates were 8 to 40 mL/min. The impact of contact force on lesion safety and efficacy was more pronounced using HPSD (60 W/8 seconds) compared with conventional ablation (30 W/45 seconds) (P = .038). During PVI, focal atrial lesions ranged in width from 4.2 to 12.5 mm and were transmural 80.8% of the time. PVI was achieved in 13 of 14 veins. Logistic regression identified that the optimal parameters for radiofrequency application were 60 to 70 W with a duration <8 seconds and <15 g contact force. Conclusions: Optimal HPSD lesions with this this flexible-tipped, force-sensing RFA catheter were created at 60 to 70 W for <8 seconds with <15 g contact force. Chronic studies are ongoing to assess radiofrequency parameter refinements and long-term lesion durability using these conditions.

Safe and effective delivery of high-power, short-duration radiofrequency ablation lesions with a flexible-tip ablation catheter.

Background: High-power, short-duration (HPSD) radiofrequency ablation (RFA) may reduce ablation time. Concerns that catheter-mounted thermocouples (TCs) can underestimate tissue temperature, resulting in elevated risk of steam pop formation, potentially limit widespread adoption of HPSD ablation. Objective: The purpose of this study was to compare the safety and efficacy of HPSD and low-power, long-duration (LPLD) RFA in the context of pulmonary vein isolation (PVI). Methods: An open-irrigated ablation catheter with a contact force sensor and a flexible-tip electrode containing a TC at its distal end (TactiFlexTM Ablation Catheter, Sensor EnabledTM, Abbott) was used to isolate the left pulmonary veins (PVs) in 12 canines with HPSD RFA (50 W for 10 seconds) and LPLD RFA (30 W for a maximum of 60 seconds). PVI was assessed at 30 minutes and 28 ± 3 days postablation. Computed tomographic scans were performed to assess PV stenosis after RFA. Lesions were evaluated with histopathology. Results: A total of 545 ablations were delivered: 252 with LPLD (0 steam pops) and 293 with HPSD RFA (2 steam pops) (P = .501). Ablation time required to achieve PVI was >3-fold shorter for HPSD than for LPLD RFA (P = .001). All 24 PVs were isolated 30 minutes after ablation, with 12/12 LPLD-ablated and 11/12 HPSD-ablated PVs still isolated at follow-up. Histopathology revealed transmural ablations for HPSD and LPLD RFA. No major adverse events occurred. Conclusion: An investigational ablation catheter effectively delivered RFA lesions. Ablation time required to achieve PVI with HPSD with this catheter was >3-fold shorter than with LPLD RFA.

A drug-induced hypotensive challenge to verify catheter-based radiofrequency renal denervation in an obese hypertensive swine model.

OBJECTIVE: Sham-controlled trials provided proof-of-principle for the blood pressure-lowering effect of catheter-based renal denervation (RDN). However, indicators for the immediate assessment of treatment success are lacking. This study sought to investigate the impact of RDN on renal renin arteriovenous difference (renal renin AV-Δ) following a hypotensive challenge (HC). METHODS: Twelve hypertensive Ossabaw swine underwent either combined surgical and chemical (n = 3) or catheter-based RDN (n = 9). A telemetry monitor was implanted to acquire hemodynamic data continuously. Before and after RDN, a sodium nitroprusside-induced HC was performed. Renal renin AV-Δ was calculated as the difference of plasma renin concentrations drawn from the renal artery and vein. RESULTS: In total, complete renal renin AV data were obtained in eight animals at baseline and six animals at baseline and 3 months of follow-up. Baseline renal renin AV-Δ correlated inversely with change in 24-h minimum systolic (- 0.764, p = 0.02), diastolic (r = - 0.679, p = 0.04), and mean (r = - 0.663, p = 0.05) blood pressure. In the animals with complete renin secretion data at baseline and follow-up, the HC increased renal renin AV-Δ at baseline, while this effect was attenuated following RDN (0.55 ± 0.34 pg/ml versus - 0.10 ± 0.16 pg/ml, p = 0.003). Renin urinary excretion remained unchanged throughout the study (baseline 0.286 ± 0.187 pg/ml versus termination 0.305 ± 0.072 pg/ml, p = 0.789). CONCLUSION: Renin secretion induced by HC was attenuated following RDN and may serve as an indicator for patient selection and guide successful RDN procedures.

In Vitro Cell Selectivity of Reversible and Irreversible: Electroporation in Cardiac Tissue.

[Figure: see text].

Absence of (sub-)acute cerebral events or lesions after electroporation ablation in the left-sided canine heart.

BACKGROUND: Irreversible electroporation (IRE) is a nonthermal ablation modality. A 200-J application can create deep myocardial lesions, but gas bubbles are created at the ablation electrode. Cerebral effects of these bubbles are unknown. OBJECTIVE: The purpose of this study was to investigate gas microemboli-induced brain lesions after IRE and radiofrequency (RF) ablation to the left side of the canine heart, using magnetic resonance imaging (MRI) and histopathology. METHODS: In 11 canines, baseline cerebral MRI scans were performed. In 9 animals, after retrograde femoral artery access, 12 ± 4 200-J IRE applications were administered in the ascending aorta. In 2 animals, 30 minutes of irrigated 30-W RF ablation using 10-30g of contact force was applied in the left ventricle. At days 1 and 5 after ablation, MRI was repeated. The brain tissue then was histopathologically examined. RESULTS: All ablations and follow-up were uneventful. Intracardiac echography confirmed gas bubble formation after each IRE application. Neurologic examination was normal. MRI scans were normal in all animals at day 1 and were normal in 10 of 11 animals at day 5. In 1 animal, a single <2-mm-diameter lesion in the right temporal region could not be excluded as a small infarct or early hemorrhagic site. Histopathologic analysis of the same region showed no pathologic changes. In all other animals, gross and microscopic pathology were normal. CONCLUSION: MRI images alone or in combination with histologic follow-up did not reveal treatment-related embolic events. Gross and microscopic pathology did not reveal evidence of treatment-related embolic events. IRE seems to be a safe ablation modality for the brain.

Comparison of branch and distally focused main renal artery denervation using two different radio-frequency systems in a porcine model.

OBJECTIVES: Anatomic placement of lesions may impact efficacy of radio-frequency (RF) catheter renal denervation (RDN). However, it is unclear if it is necessary to perform treatments post bifurcation with systems that may provide deeper penetration to achieve successful RDN. METHODS: Sixteen domestic swine (n=16) were randomly assigned to 4 groups: 1) 8 lesions created in the branch arteries using the Spyral catheter (SP8); 2) 8 lesions created in the branch arteries plus 4 lesions created in the main artery using the SP catheter (SP12); 3) 8 lesions created in the main artery using the EnligHTN catheter with the distal position as close as possible to the bifurcation (EN8); and 4) 12 lesions created in the main artery using the EN catheter with the distal position as close as possible to the bifurcation (EN12). RESULTS: Each arm showed statistically significant changes in kidney norepinephrine (NE, ng/g) between treated kidneys vs. untreated contralateral control. There were no statistically significant differences in tissue NE% reductions across each arm based on catheter, anatomic location, & number of lesions (p=0.563): EN8 -74±34%, EN12 -95±3%, SP8 -76±16%, SP12 -82±17% (p=0.496). A total of 46 lesions were measured for lesion depth: EN main (3.3±2.8mm) vs. SP branch (2.0±1.0mm, p=0.039), SP main (2.9±1.6mm) vs. SP branch (p=0.052), and EN main vs. SP main (p=0.337). CONCLUSIONS: Distally-focused main renal artery treatment using the EN system appears to be equally efficacious in reducing tissue NE levels compared with SP treatment in the branches plus main renal arteries, advocating for device-specific procedure execution.

Catheter-based radio-frequency renal nerve denervation lowers blood pressure in obese hypertensive swine model.

OBJECTIVES: Radio-frequency renal denervation (RDN) therapy is under investigation for the treatment of uncontrolled hypertension. Data in hypertensive, drug-naïve large animal models using RDN is limited. METHODS: A cohort of Ossabaw swine (N = 9) was implanted with telemetry monitors, enrolled on a high calorie-feed regimen and randomly assigned to RDN. Blood pressure (BP) data were separated and analyzed according to the following epoch definitions: 24-h (h), most-active-h, light-h, and dark-h. RESULTS: The mean weight increased by 45% from 86.5 ±â€Š2.5 kg at telemetry implant (day 87) to 125.2 ±â€Š4.5 kg at time of RDN therapy (day 227). Hypertension developed in all swine (24-h BP: 169.5/128.3 ±â€Š5.8/5.1 mmHg pre-RDN). RDN resulted in significant reductions in noradrenaline kidney tissue concentration by 63%. Significant BP reductions were documented at 45 days post-RDN in all defined interday epochs, except for the dark-h period. The most pronounced SBP/DBP reduction was 12.4/11.2 mmHg (P < 0.05), observed during the most-active-h period. Animals continued to gain weight after the RDN procedure to the end of the study at 90 days (125.2 ±â€Š4.5-138.5 ±â€Š6.6 kg, P < 0.001). At 90 days post-RDN, the mean 24-h BP returned near pre-RDN baseline values. Given the strong relationship of BP to weight (R = 0.87, P < 0.001), group mean SBP/DBP was normalized by weight resulting in significant and continued reductions at both 45 and 90 days post-RDN across all intradaily epochs. CONCLUSION: Catheter-based RDN, using a multielectrode system, resulted in a significant reduction in 24-h BP in this drug-naïve, hypertensive animal model.

Contact sensing provides a highly accurate means to titrate radiofrequency ablation lesion depth.

BACKGROUND: Transmural lesions are essential for efficacious ablation. There are, however, no accurate means to estimate lesion depth. OBJECTIVE: Explore use of the electrical coupling index (ECI) from the EnSite Contact™ System as a potential variable for lesion depth estimation. METHODS: Radiofrequency (RF) ablation lesions were created in atria and the thighs of swine using an irrigated RF catheter. Power was 30 W for 20 or 30 seconds intracardiac and 30-50 W for 10-60 seconds for the thigh. Intracardiac, the percentage change in ECI during ablation was compared with transmurality and collateral damage occurrence. For the thigh model, an algorithm estimating lesion depth was derived. Factors included: power, duration, and change in the ECI subcomponents (ΔECI+) during ablation. The ΔECI+ algorithm was compared to one using power and duration (PD) alone. RESULTS: Intracardiac, lesions with ≥12% reduction in ECI were more likely to be transmural (92.3% vs. 59.4%, P < 0.001). Twenty-second lesions were less likely to cause collateral damage compared to 30 seconds (33% vs. 70%, P = 0.003), while transmurality was similar. With the thigh model, ΔECI+ had a better correlation than the PD algorithm (P < 0.01). Accuracy of the ΔECI+ algorithm was unimproved with inclusion of tip orientation, while PD improved (R(2) = 0.64). DISCUSSION: Change in ECI provides evidence of transmural versus nontransmural swine intracardiac atrial lesions. A lesion depth estimation algorithm using ECI subcomponents is unaffected by tip orientation and is more accurate than using PD alone. CONCLUSION: Use of ECI as a factor in a lesion depth algorithm may provide clinically valuable information regarding the efficacy of intracardiac RF ablation lesions.

Field verification of sound attenuation modeling and air emission testing in support of missile motor disposal activities.

The U.S. Department of Defense-approved activities conducted at the Utah Test and Training Range (UTTR) include both operational readiness test firing of intercontinental ballistic missile (ICBM) motors, as well as the destruction of obsolete or otherwise unusable ICBM motors through open burn/open detonation (OB/OD). Within the Utah Division of Air Quality, these activities have been identified as having the potential to generate unacceptable noise levels, as well as significant amounts of volatile organic compounds (VOCs). Hill Air Force Base, UT, has completed a series of field tests at the UTTR in which sound-monitoring surveillance of OB/OD activities was conducted to validate the Sound Intensity Prediction System (SIPS) model. Using results generated by the SIPS model to support the decision to detonate, the UTTR successfully disposed of missile motors having an aggregate net explosive weight (NEW) of 81,374 lb without generating adverse noise levels within populated areas. In conjunction with collecting noise-monitoring data, air emissions were collected to support the development of air emission factors for both static missile motor firings and OB/OD activities. Through the installation of 15 ground-based air samplers, the generation of combustion-fixed gases, VOCs, and chlorides was monitored during the 81,374-lb NEW detonation event. Comparison of field measurements to predictions generated from the US Navy energetic combustion pollutant formation model, POLU4WN, indicated that, as the detonation fire ball expanded, organic compounds, as well as CO, continued to oxidize as the combustion gases mixed with ambient air. VOC analysis of air samplers confirmed the presence of chloromethane, vinyl chloride, benzene, toluene, and 2-methyl-1-propene. Qualitative chloride analysis indicated that gaseous HCl was generated at low concentrations, if at all.

Field validation of sound mitigation models and air pollutant emission testing in support of missile motor disposal activities.

The U.S. Department of Defense approved activities conducted at the Utah Test and Training Range (UTTR) include both operational readiness test firing of intercontinental ballistic missile motors as well as the destruction of obsolete or otherwise unusable intercontinental ballistic missile motors through open burn/open detonation (OB/ OD). Within the Utah Division of Air Quality, these activities have been identified as having the potential to generate unacceptable noise levels, as well as significant amounts of hazardous air pollutants. Hill Air Force Base, UT, has completed a series of field tests at the UTTR in which sound-monitoring surveillance of OB/OD activities was conducted to validate the Sound Intensity Prediction System (SIPS) model. Using results generated by the SIPS model to support the decision to detonate, the UTTR successfully disposed of missile motors having an aggregate net explosive weight (NEW) of 56,500 lbs without generating adverse noise levels within populated areas. These results suggest that, under appropriate conditions, missile motors of even larger NEW may be detonated without exceeding regulatory noise limits. In conjunction with collecting noise monitoring data, air quality data was collected to support the development of air emission factors for both static missile motor firings and OB/OD activities. Through the installation of 15 ground-based air samplers, the generation of combustion fixed gases, hazardous air pollutants, and chlorides were monitored during the 56,500-lb NEW detonation event. Comparison of field measurements to predictions generated from the U.S. Navy's energetic combustion pollutant formation model, POLU4WN, indicated that, as the detonation fireball expanded from ground zero, organic compounds as well as carbon monoxide continued to oxidize as the hot gases reacted with ambient air. Hazardous air pollutant analysis of air samplers confirmed the presence of chloromethane, benzene, toluene, 1,2-propadiene, and 2-methyl-l-propene, whereas the absence of hydrogen chloride gas suggested that free chlorine is not generated during the combustion process.