Initial experience and follow up on the PolarX cryoablation system compared to the established Arctic Front cryoablation system in PVI ablations

Introduction Pulmonary vein isolation (PVI) with cryoablation was shown to be comparable to radiofrequency ablation (RF) in terms of safety and outcome for patients with atrial fibrillation (AF), so that both techniques are recommended equally by the current guidelines. A new cryoablation system PolarX® was introduced in 2020. We analysed the first patients, who underwent ablation with the new system with respect to procedural and safety outcome and evaluated the freedom from arrhythmia occurrence in the first 6 months compared to patients treated with the established Arctic Front Advance® cryoablation system. Methods We included the consecutive 44 patients who underwent cryoablation with the new PolarX® cryoablation system (28mm) and 24 patients who underwent cryoablation with the established Arctic Front Advance® cryoablation system (28mm) for paroxysmal AF. We retrospectively analysed baseline characteristics, procedural- and safety data. In 5 patients of each group an additional high-density 3D-mapping was performed, evaluating the scar-area after cryoablation in both groups (figure 1A+B). After 6 months the freedom of AF (by 7d-Holter-ECG) was evaluated in both groups. Results Baseline, procedural characteristics and results are listed in table 1. Mean total procedure duration (“door-to-door-time”) was significantly shorter in the PolarX group compared to the Arctic-Front group (136±34min vs. 163±43min; p<0.05). Number of freezes required to achieve isolation of all pulmonary veins (PVs) and cumulative freezing time was comparable in both groups. Minimal achieved temperatures were significantly lower in the PolarX group vs. ArcticFront group. The scar-area analyzed by 3D-mapping post ablation did not differ in the two groups. Complication rates as well as clinical outcome (freedom from AF) were low and did not differ in the Kaplan-Meier analysis (table 1; figure 1C). Conclusion Based on these initial results, cryoablation with the PolarX cryoballoon seems to be comparably effective and safe, with a significantly shorter procedure time and significantly lower achieved temperatures. Nevertheless, future controlled trials with a longer follow-up period will be necessary to evaluate long-term effectiveness. FUNDunding Acknowledgement Type of funding sources: None.

Sox9 and Rbpj differentially regulate endothelial to mesenchymal transition and wound scarring in murine endovascular progenitors

Endothelial to mesenchymal transition (EndMT) is a leading cause of fibrosis and disease, however its mechanism has yet to be elucidated. The endothelium possesses a profound regenerative capacity to adapt and reorganize that is attributed to a population of vessel-resident endovascular progenitors (EVP) governing an endothelial hierarchy. Here, using fate analysis, we show that two transcription factors SOX9 and RBPJ specifically affect the murine EVP numbers and regulate lineage specification. Conditional knock-out of Sox9 from the vasculature (Sox9fl/fl/Cdh5-CreERRosaYFP) depletes EVP while enhancing Rbpj expression and canonical Notch signalling. Additionally, skin wound analysis from Sox9 conditional knock-out mice demonstrates a significant reduction in pathological EndMT resulting in reduced scar area. The converse is observed with Rbpj conditionally knocked-out from the murine vasculature (Rbpjfl/fl/Cdh5-CreER RosaYFP) or inhibition of Notch signaling in human endothelial colony forming cells, resulting in enhanced Sox9 and EndMT related gene (Snail, Slug, Twist1, Twist2, TGF-β) expression. Similarly, increased endothelial hedgehog signaling (Ptch1fl/fl/Cdh5-CreER RosaYFP), that upregulates the expression of Sox9 in cells undergoing pathological EndMT, also results in excess fibrosis. Endothelial cells transitioning to a mesenchymal fate express increased Sox9, reduced Rbpj and enhanced EndMT. Importantly, using topical administration of siRNA against Sox9 on skin wounds can substantially reduce scar area by blocking pathological EndMT. Overall, here we report distinct fates of EVPs according to the relative expression of Rbpj or Notch signalling and Sox9, highlighting their potential plasticity and opening exciting avenues for more effective therapies in fibrotic diseases.

Scar endometriosis: a mystery entity

Scar Endometriosis is described as having an active endometrial tissue at the scar area outside the uterine cavity. Corner stone for diagnosis is proper history, clinical examination and suspicion-based imaging. Caesarean scar endometriosis (CSE) usually seen following procedures like caesarean sections, hysterectomies. Time of presentation can be very variable so yet times difficult to suspect. Once suspected Convincing patient that they have active glands other than in uterine cavity is not easy. Hence proper imaging and biopsy is needed to backup for thorough counselling and treatment to improve the quality of life.

Determination of scar area using native and post contrast T1 mapping: a validation study

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Goethe University Hospital Introduction Late gadolinium enhancement (LGE) with Full Width Half Maximum (FWHM) is the standard imaging method for the measurement of the scar area in ischemic heart disease, a major determinant of adverse outcome. T1 mapping techniques have become increasingly applied in everyday clinical practice. Agreement in area quantification between T1 mapping and LGE for the scar extent has not been systematically assessed. Purpose This study aims to ascertain concordance between the area determined by native and post contrast T1 mapping against LGE to determine scar area in patients with a prior myocardial infarction. It also examines intra and inter-observer reproducibility for these two methods. Methods Subendocardial scar was evaluated in 132 patients with ischemic heart disease using LGE, native and post contrast T1 mapping in 3 short axis slices. Native and postcontrast T1 mapping was performed using GoetheCVI®MOLLI sequence (Gadovist® 0.1mmol/kg). FWHM method was applied for LGE and compared with the manually delineated area of scar in native and postcontrast T1 mapping acquisitions within the identical slices. The presence of the scar was defined as LGE >3% of the myocardial mass. Bland-Altman methods were employed to assess concordance between techniques and reproducibly between observers. Results In comparison to LGE, area measurements in native T1 acquisitions underestimated infarct size (9,1% vs 12,6%, p = 0.01), while postcontrast T1 overestimated it (19,4% vs 12,6%, p < 0.001). The disparity between the measurements was accentuated with larger scar areas (Figure 1). Intraobserver reproducibility (native T1: intra/inter MD ± SD, CoV, postcontrast T1: intra/inter) was similar with both methods, whereas interobserver variability for native T1 mapping acquisition was worse. Conclusions We demonstrate that measurements of the area of myocardial scar by T1 mapping acquisitions yield considerably different results in comparison to the standard LGE-based FWHM method. High observer agreement indicates that these differences are genuinely related to the type of the underlying acquisition and the differences in detected signal. The approaches are not interchangeable. However, the importance of these results for predicting patient outcome is yet to be elucidated. Nonetheless, these results were consistent in the inter and intraobserver analysis for post contrast T1 mapping, although native T1 mapping failed to show similar consistency. Figure 1: Bland-Altmann plot of differences (mean ± upper and lower limit of agreement-LOA) in scar area extent (percentage) between LGE and native T1 mapping (A), LGE and post contrast T1 mapping (B). The difference increases linearly for larger scar areas when using post contrast mapping, which does not apply for native mapping. Abstract Figure 1

Effect of herpes simplex keratitis scar location on bilateral corneal nerve alterations: an in vivo confocal microscopy study

AimsTo evaluate the impact of herpes simplex virus (HSV)-induced scar location on bilateral corneal nerve alterations using laser in vivo confocal microscopy (IVCM).MethodsCentral and peripheral corneal subbasal nerve density (CSND) were assessed bilaterally in 39 patients with unilateral HSV-induced corneal scars (21 central scars (CS), 18 peripheral scars (PS)) using IVCM. Results were compared between patients and 24 age-matched controls. CSND was correlated to corneal sensation for all locations.ResultsOverall patients revealed significant decrease of CSND in the central and peripheral cornea (9.13±0.98 and 6.26±0.53 mm/mm2, p<0.001), compared with controls (22.60±0.77 and 9.88±0.49 mm/mm2). CS group showed a decrease in central (8.09±1.30 mm/mm2) and total peripheral nerves (5.15±0.62 mm/mm2) of the affected eyes, whereas PS group demonstrated a decrease in central (10.34±1.48 mm/mm2) and localised peripheral nerves only in the scar area (4.22±0.77 mm/mm2) (all p<0.001). In contralateral eyes, CSND decreased in the central cornea of the CS group (16.88±1.27, p=0.004), and in the peripheral area, mirroring the scar area in the affected eyes of the PS group (7.20±0.87, p=0.032). Corneal sensation significantly decreased in the whole cornea of the affected, but not in contralateral eyes (p<0.001). A positive correlation between CSND and corneal sensation was found in all locations (p<0.001).ConclusionsPatients with HSV scar demonstrate bilateral CSND decrease as shown by IVCM. CSND and corneal sensation decrease in both central and peripheral cornea in affected eyes, although only in the scar area in PS group. Interestingly, diminishment of CSND was found locally in the contralateral eyes, corresponding and mirroring the scar location in the affected eyes.

Value of Crystal Vue technique in detecting the placenta accreta spectrum located in c-section scar area

Aims: Excessive placental invasion is a life-threatening obstetric disease. Determining the extent of placental villi invasion prenatally is crucial for formulating a surgical plan for pregnant women. The objective of this study was to explore the diagnostic accuracy of the Crystal Vue technique combined with two-dimensional (2D) ultrasound in detecting the degree of placenta accreta spectrum (PAS) located in the C-section scar area.Materials and methods: Twenty-seven pregnant women with a strong suspicion of PAS underwent 2D ultrasound combined with a Crystal Vue examination. The diagnosis of 2D ultrasound alone and Crystal Vue combined with 2D ultrasound was statistically calculated, respectively. Cohen’s kappa (k) was used to measure the consistency between these two ultrasound diagnosis and the postoperative diagnosis.Results: The postoperative diagnosis of 27 pregnant women was as follows: 6 cases of placental accreta, 11 cases of placental increta, 2 cases of placental percreta, 2 cases of placental accrete and placental increta, 2 cases of placental accreta and placental percreta, and 4 cases without PAS. Compared with the postoperative diagnosis, 20 cases (74.07%) were correctly diagnosed by 2D ultrasound alone, 6 cases were misdiagnosed, and one case the diagnosis was incomplete, which were substantially consistent with the postoperative diagnosis (k=0.612, p<0.01). Twenty-six cases (96.30%) were correctly diagnosed by Crystal Vue combined with 2D ultrasound; only one case was incomplete diagnosed which was almost perfectly consistent with the postoperative diagnosis (k=0.934, p<0.01).Conclusions: Combining the Crystal Vue technique with 2D ultrasound can improve the diagnostic accuracy of ultrasound for detecting all types of PAS located in C-section scar area.

P357Epicardial abnormal electrical activity in unselected patients with ischemic ventricular tachycardia: a pilot mapping study

Background radiofrequency catheter ablation (RFA) on the endocardial ventricular surface is widely used for post-myocardial infarction (post-MI) ventricular tachycardia (VT) treatment. It has been described that about 10% of patients with post-MI require additional epicardial ablation for successful VT termination. However, there is still lack of data regarding the extent of scarring and the presence of local abnormal ventricular electrical activity (LAVA, low-voltage and/or fractionated signals) on the epicardial surface in patients with ischemic VT. Purpose to assess the extent of epicardial electrophysiological substrate in patients with remote myocardial infarction and indications for VT ablation. Methods thirteen out of 59 patients with sustained ischemic VT (12 men; mean age 59,9 ± 9,5) and without previous cardiac surgery signed an informed consent to undergo epicardial mapping and comprized the study population. Endocardial access was used previously as primary method in 4 patients ICD/ CRT-D had been previously implanted in 11 patients: mean left ventricle ejection fraction was 38,8 ± 10,6 %: hemodynamically unstable VT was present in 10 patients; the most frequent scar localization by ECG and transthoracic echocardiography – left ventricle (LV) inferior wall (10 patients), LV lateral wall – (7 patients). All patients underwent full clinical evaluation. Electrophysiological procedure and catheter ablation was performed under general anesthesia. Epicardial access was obtained through percutaneous subxyphoid puncture. Voltage mapping of endocardial and epicardial surfaces was performed. Maps were evaluated for the presence of LAVA. Ablation was performed at sites of LAVA on either side of the ventricular wall. Results epicardial access was successful in 12 patients. Bi- and unipolar mapping was successfully performed and analyzed in 11 subjects. LAVA was present in all but one patient on endocardial surface and in 9 (82%) out of 12 patients on epicardial surface. Localization of endocardial and epicardial LAVA coincided in 8 (67%) patients suggesting transmural ischemic scar. One patient had only epicardial scar, 1 patient had septal endocardial scar without LAVA on the epicardial surface. In one patient LAVA sites were localized on different left ventricle walls. More extensive unipolar than bipolar endocardial scar area was found (11,8 (IQR:2,0;31,6) vs 45,8 (IQR:17,1;86,5) сm2; р=0,03). Epicardial unipolar scar area prevailed over bipolar scar area: median 46.0 cm2 (IQR: 15.9;55.5) vs 107.7 cm2 (IQR: 84.3;168.9) р=0,04. LAVA epicardial area was wider than endocardial: 19.7 cm2 (IQR: 2.3; 29.7) vs 4.1 cm2 (IQR: 0.4; 23.8) р=0.03. Conclusion according to the results of our pilot study in unselected patients with ischemic VT, epicardial arrhythmogenic substrate was detected in 82% of cases. Epicardial LAVA area significantly prevailed over endocardial LAVA area.

130Long-term outcomes of ventricular tachycardia substrate ablation incorporating hidden slow conduction analysis

Introduction Ventricular tachycardia substrate ablation (VTSA) incorporating hidden slow conduction (HSC) analysis allows further arrhythmic substrate identification. This study evaluates whether the analysis and elimination of HSC electrograms (HSC-EGMs) during VTSA procedures result in better short and long-term outcomes. Methods Consecutive patients (n = 70, 63% ischaemic, 64 ± 14.6 years) undergoing VTSA were prospectively included. Bipolar EGMs with &gt;3 deflections and duration &lt;133 ms were considered as potential HSC-EGM, if located within/surrounding the scar area. Whenever a potential HSC-EGM was identified, a double ventricular extrastimulus was delivered. If a local potential showed up as a delayed component, it was annotated as HSC-EGM. The incidence of HSC-EGM in core, border-zone, and normal-voltage regions was determined. Ablation was delivered at conducting channel entrances and HSC-EGMs. Procedure time, radiofrequency time, VT inducibility after VTSA and VT recurrence at 12 months after the procedure were compared with data from a historic control group (n = 66, 70% ischaemic, 65.2 ± 12 years). Results 5076 EGMs were analyzed. 1029 (20.2%) qualified as potential HSC-EGM, and 453 of them were tagged as HSC-EGMs. Scars in patients with HSC-EGMs (n = 43, 61.4%) were smaller (39.66 ± 28.2 vs 69.4 ± 38.2 cm2; p = 0.005) and more heterogeneous (core/scar area ratio 0.24 ± 0.2 vs 0.43 ± 0.17; p = 0.03). 29.6% of HSC-EGMs were located in normal-voltage tissue; 83.5% were targeted for ablation. Patients undergoing VTSA incorporating HSC analysis needed less procedure time (213 ± 75 vs 242 ± 60 min; p = 0.018), less RF time (15.9 ± 10 vs 25 ± 12,7 minutes; p &lt; 0.001), had a lower rate of VT inducibility (27.5% vs 51.5%; p = 0.005) and a higher 2-year VT/VF-free survival (82.8% vs 59.7%; log rank p = 0.047) after VTSA than the historic controls . Conclusion VTSA incorporating HSC analysis allowed further arrhythmic substrate identification (especially in normal-voltage areas) and resulted in increased VTSA efficiency and better short and long-term outcomes. Abstract Figure. VT Recurrence-Free Survival