Comparison of new-generation renal artery denervation systems: assessing lesion size and thermodynamics using a thermochromic liquid crystal phantom model

Aims: The aim of this study was to evaluate and compare lesion dimensions and thermodynamics of the new-generation multi-electrode Symplicity Spyral and the new-generation multi-electrode EnligHTN renal artery denervation systems, using a thermochromic liquid crystal phantom model. Methods and results: A previously described renal artery phantom model was used as a platform for radiofrequency ablation. A total of 32 radiofrequency ablations were performed using the multi-electrode Symplicity Spyral (n=16) and the new-generation EnligHTN systems (n=16). Both systems were used as clinically recommended by their respective manufacturer. Lesion borders were defined by the 51°C isotherm. Lesion size (depth and width) was measured and compared between the two systems. Mean lesion depth was 2.15±0.02 mm for the Symplicity Spyral and 2.32±0.02 mm for the new-generation EnligHTN (p-value <0.001). Mean lesion width was 3.64±0.08 mm and 3.59±0.05 mm (p-value=0.61) for the Symplicity Spyral and the new-generation EnligHTN, respectively. Conclusions: The new-generation EnligHTN system produced lesions of greater depth compared to the Symplicity Spyral under the same experimental conditions. Lesion width was similar between both systems. Achieving greater lesion depth by use of the new-generation EnligHTN may result in better efficacy of renal artery denervation

Comparison of two different radiofrequency ablation systems for renal artery denervation: Evaluation of short-term and long-term follow up

Objectives: To assess the clinical efficacy of renal artery denervation (RAD) in our center and to compare the efficacy of two different radiofrequency (RF) systems. Background: Several systems are available for RF renal denervation. Whether there is a difference in clinical efficacy among various systems remains unknown. Methods: Renal artery denervation was performed on 43 patients with resistant hypertension using either the single electrode Symplicity Flex (n = 20) or the multi-electrode EnligHTN system (n = 23). Median post-procedural follow-up was 32.93 months. The primary outcome was post-procedural change in office blood pressure (BP) within 1 year (short-term follow-up). Secondary outcomes were change in office BP between 1 and 4 years (long-term follow-up) and the difference in office BP reduction between the two systems at each follow-up period. Results: For the total cohort, mean baseline office BP (systolic/diastolic) was 174/94 mmHg. At follow-up, mean changes in office BP from baseline were −19.70/−11.86 mmHg (P < 0.001) and −21.90/−13.94 mmHg (P < 0.001) for short-term and long-term follow-up, respectively. The differences in office BP reduction between Symplicity and EnligHTN groups were 8.96/1.23 mmHg (P = 0.42 for systolic BP, P = 0.83 for diastolic BP) and 9.56/7.68 mmHg (P = 0.14 for systolic BP, P = 0.07 for diastolic BP) for short-term and long-term follow-up, respectively. Conclusions: In our cohort, there was a clinically significant office BP reduction after RAD, which persisted up to 4 years. No significant difference in office BP reduction between the two systems was found

Transcatheter non-contact microwave ablation may enable circumferential renal artery denervation while sparing the vessel intima and media

Aims: Trials of transcatheter renal artery denervation (RDN) have failed to show consistent antihypertensive efficacy. Procedural factors and limitations of radiofrequency ablation can lead to incomplete denervation. The aim of the study was to show that non-contact microwave catheter ablation could produce deep circumferential perivascular heating while avoiding injury to the renal artery intima and media. Methods and results: A novel microwave catheter was designed and tested in a renal artery model consisting of layers of phantom materials embedded with a thermochromic liquid crystal sheet, colour range 50-78°C. Ablations were performed at 140 W for 180 sec and 120 W for 210 sec, delivering 25,200 J with renal arterial flow at 0.5 L/min and 0.1 L/min. Transcatheter microwave ablations 100-160 W for 180 sec were then performed in the renal arteries of five sheep. In vitro, ablations at 140 W and 0.5 L/min flow produced circumferential lesions 5.9±0.2 mm deep and 19.2±1.5 mm long with subendothelial sparing depth of 1.0±0.1 mm. In vivo, transcatheter microwave ablation was feasible with no collateral visceral thermal injury. There was histological evidence of preferential outer media and adventitial ablation. Conclusions: Transcatheter microwave ablation for RDN appears feasible and provides a heating pattern that may enable more complete denervation while sparing the renal arterial intima and media

Local Electrogram Fractionation and Post-Infarct VT

Background: Post-myocardial infarction (MI) remodeling contributes to increased electrophysiological and structural heterogeneity and arrhythmogenesis. Utilising the post-infarct ovine model our aim was to determine unipolar electrogram frequency characteristics consequent to this remodeling and the development of Ventricular Tachycardia (VT). Methods and Results: Mapping studies were performed on 14 sheep at >1 month post-MI induction. Sheep were divided into VT inducible (n=7) and non-inducible (n=7) groups. Multielectrode needles (n=20) were deployed within and surrounding ventricular scar for electrophysiological assessment of electrogram amplitude and width. Spectral analysis of electrograms was undertaken using wavelet and fast fourier transformations (WFFT) to calculate root mean square (RMS) power intervals spanning 0-300Hz in 20Hz intervals. Quantitative assessment between electrophysiological and histological parameters including collagen density, and structural organization of the myocardium was performed. Increasing myocardial scar density resulted in attenuation of electrogram amplitude and RMS values. (all p<0.01). Between groups there were no differences in electrogram amplitude (p=0.37), however WFFT analysis revealed significantly higher RMS values in the VT group (p<0.05) in association with high frequency fractional components of the electrogram. As scar density increased, greater between-group differences in RMS were observed spanning this high frequency (200-280Hz) spectrum and which were proportionally dependent on the degree of structural disorganisation of the myocardium (p<0.001) and number of extrastimuli required to induce VT (p<0.05). Conclusion: High frequency unipolar electrogram spectral characteristics were quantitatively co-influenced by the presence of fibrosis and degree of myocardial structural dissorganisation and were associated with the propensity for development of VT

Spatial Characterization of Electrogram Morphology from Transmural Recordings in the Intact Normal Heart

The electrophysiological cardiac data relating to this research are included in the file named "pouliopoulos_etal_propagation_data_plosone.xlsx"Purpose: Unipolar (UE) and bipolar electrograms (BE) are utilized to identify arrhythmogenic substrate. We quantified the effect of increasing distance from the source of propagation on local electrogram amplitude; and determined if transmural electrophysiological gradients exist with respect to propagation and stimulation depth. Methods: Mapping was performed on 5 sheep. Deployment of >50 quadripolar transmural needles in the LV were located in Cartesian space using Ensite. Contact electrograms from all needles were recorded during multisite bipolar pacing from epicardial then endocardial electrodes. Analysis was performed to determine stimulus distance to local activation time, peak negative amplitude (V-P¬), and peak-peak amplitude (VP-P) for (1) unfiltered UE, and (2) unfiltered and 30Hz high-pass filtered BEs. Each sheep was analysed using repeated ANOVA. Results: Increasing distance from the pacing sites led to significant (p0.01) during endocardial stimulation, and 2.3±2.4ms (UE) and 1.8±3.7ms (BE) during epicardal stimulation (all p VP-P. Conduction propagates preferentially via the epicardium during stimulation and is believed to contribute to a transmural amplitude gradient

Spatial Characterization of Electrogram Morphology from Transmural Recordings in the Intact Normal Heart

Purpose: Unipolar (UE) and bipolar electrograms (BE) are utilized to identify arrhythmogenic substrate. We quantified the effect of increasing distance from the source of propagation on local electrogram amplitude; and determined if transmural electrophysiological gradients exist with respect to propagation and stimulation depth. Methods: Mapping was performed on 5 sheep. Deployment of >50 quadripolar transmural needles in the LV were located in Cartesian space using Ensite. Contact electrograms from all needles were recorded during multisite bipolar pacing from epicardial then endocardial electrodes. Analysis was performed to determine stimulus distance to local activation time, peak negative amplitude (V-P¬), and peak-peak amplitude (VP-P) for (1) unfiltered UE, and (2) unfiltered and 30Hz high-pass filtered BEs. Each sheep was analysed using repeated ANOVA. Results: Increasing distance from the pacing sites led to significant (p0.01) during endocardial stimulation, and 2.3±2.4ms (UE) and 1.8±3.7ms (BE) during epicardal stimulation (all p VP-P. Conduction propagates preferentially via the epicardium during stimulation and is believed to contribute to a transmural amplitude gradient

Quantitative spectral assessment of intracardiac electrogram characteristics associated with post infarct fibrosis and ventricular tachycardia.

BACKGROUND:Post-myocardial infarction (MI) remodeling contributes to increased electrophysiological and structural heterogeneity and arrhythmogenesis. Utilising the post-infarct ovine model our aim was to determine unipolar electrogram frequency characteristics consequent to this remodeling and the development of Ventricular Tachycardia (VT). METHODS AND RESULTS:Mapping studies were performed on 14 sheep at >1 month post-MI induction. Sheep were divided into VT inducible (n = 7) and non-inducible (n = 7) groups. Multielectrode needles (n = 20) were deployed within and surrounding ventricular scar for electrophysiological assessment of electrogram amplitude and width. Spectral analysis of electrograms was undertaken using wavelet and fast fourier transformations (WFFT) to calculate root mean square (RMS) power intervals spanning 0-300Hz in 20Hz intervals. Quantitative assessment between electrophysiological and histological parameters including collagen density, and structural organization of the myocardium was performed. Increasing myocardial scar density resulted in attenuation of electrogram amplitude and RMS values. (all p<0.01). Between groups there were no differences in electrogram amplitude (p = 0.37), however WFFT analysis revealed significantly higher RMS values in the VT group (p<0.05) in association with high frequency fractional components of the electrogram. As scar density increased, greater between-group differences in RMS were observed spanning this high frequency (200-280Hz) spectrum and which were proportionally dependent on the degree of structural disorganisation of the myocardium (p<0.001) and number of extrastimuli required to induce VT (p<0.05). CONCLUSION:High frequency unipolar electrogram spectral characteristics were quantitatively co-influenced by the presence of fibrosis and degree of myocardial structural dissorganisation and were associated with the propensity for development of VT

Spatial representation of sub-endocardial electrogram parameters during sub-endocardial pacing from the apex (left panels) and base of the left ventricle (right panels).

<p>Two dimensional space is based on spherical coordinates derived from needle locations, representing elevation (−1 =  apex to +1 =  base), and azimuth (−2 =  mid lateral to +2 =  anterior). Numbered contours represent parameters derived from unipolar contact electrograms represented in milliseconds (ms) for activation time (AT) and millivolts (mV) for V_-P and V_P-P corresponding to panels from top to bottom respectively. Solid arrows represent preferential path of activation. Dotted arrows represent the approximate electrophysiological gradient of V_-P and V_P-P away from the stimulus site.</p

Two representative stained histological sections using haematoxylin-eosin of normal myocardium from different sites in the Ovine left ventricle.

<p>Left: unprocessed image. Right: convolved images identifying transmural anisotropy vectors in two dimensions from multiple sites indicated (circles) within each section. Circles arranged from epicardium (top) to endocardium (bottom). Anisotropy vectors orientated vertically at epicardial layer with distinct transitioning to horizontal orientation at the mid myocardial layer followed by diagonal orientation at the endocardial layer.</p

Transmural comparison of activation time between the epicardial and endocardial layer (shown as difference ΔAT) at various distances from the stimulus site during endocardial and epicardial pacing.

<p>Comparisons shown are: A. Unipolar and B. Bipolar minimally filtered electrograms.</p