Scar Area Research Articles

The experience of metroplasty at the stage of delivery in pregnant women with two cesarean section operations in the anamnesis

The purpose of our study is to evaluate the effectiveness of metroplasty at the stage of abdominal delivery in women with a history of two cesarean section operationsMaterials and methods. From 2020 to 2022, 150 pregnant women were examined. The patients were divided into 3 groups: the first group - pregnant women with a history of cesarean section, the second group – pregnant women with two cesarean sections. In these groups, metroplasty was performed at the stage of delivery. The third control group consisted of pregnant women with a history of two cesarean sections who underwent surgical delivery without excision of scar tissue in the lower segment.Metroplasty was performed before fetal extraction with a whole fetal bladder in accordance with the patent "Method of metroplasty during operative delivery in women with two or more cesarean sections".In order to study the dynamics of changes in scar thickness, all women underwent ultrasound examination 2 hours later, on the third day after delivery, and 6 months after delivery.The results of the study. Resection of the scar area on the uterus during repeated cesarean section improves the residual thickness of the myometrium, which is determined by ultrasound 6 months after surgery. This technique allows you to form a functionally consistent scar on the uterus after two cesarean section operations.

Runx2 Suppresses Astrocyte Activation and Astroglial Scar Formation After Spinal Cord Injury in Mice.

After spinal cord injury, astrocytes undergo a reactive process and form an astroglial scar, which impedes the regeneration of axons. The role of Runx2 in promoting the transformation of astrocytes in the central nervous system is well-established. However, it remains unclear whether Runx2 also plays a role in the development of astroglial scar, and the precise underlying mechanism has yet to be identified. Recently, our study using cell culture and animal models has demonstrated that Runx2 actually suppresses astrocyte activation and the formation of astroglial scar following injury. The initial results demonstrated an increase in the expression of Runx2 in astrocytes following in vivo injury. Subsequently, the overexpression of Runx2 resulted in the inhibition of astrocyte activation, reduction in the total area of astroglial scar, and restoration of neural function after 14 days of injury. However, these effects were reversed by CADD522. These findings indicate that Runx2 could potentially serve as a therapeutic intervention for spinal cord injury (SCI). Furthermore, our findings suggest that the Nuclear-matrix-targeting signal (NMTS) of Runx2 is associated with its effect. In summary, the study's results propose that targeting Runx2 may be a promising treatment approach for reactive astrocytes and astroglial scar in the recovery of SCI.

Scar tissue characterization to predict arrhythmia recurrence in patients undergoing ventricular tachycardia ablation: cardiac computed tomography compared with cardiac magnetic resonance

Abstract Background The role of imaging in evaluating patients undergoing ventricular tachycardia (VT) ablation is crucial for planning, procedural success, and clinical outcomes. In daily practice, cardiac computed tomography (CCT) assessing wall thinning and late iodine uptake (LI) and cardiac magnetic resonance (CMR) assessing late-gadolinium enhancement (LGE) are most commonly implemented. However, data comparing the two imaging modalities for scar tissue characterization is scarce. Aims To compare the performance of both imaging modalities for scar tissue characterization in ischemic (ICM) and non-ischemic (NICM) patients undergoing VT ablation and predict procedural outcomes. Methods In a retrospective analysis, consecutive patients undergoing both CCT and LGE-CMR before scheduled VT ablation were included. The presence and extent of scar was assessed by means of each imaging modality using dedicated softwares (MUSIC and ADAS). To compare scar distribution and agreement between the two modalities, a scar classification scheme was used for all 17 AHA segments: 0 points (no scar present), 1 point (scar <50% of total segment area), 2 points (scar representing 50-99% of total segment area) or 3 points (scar present in 100% of the segment area).<scar<100%)><scar<100%> Results 36 patients (67±10 years; 97% male; LVEF 39±10%; 72% ischemic) undergoing CCT and LGE-CMR before scheduled VT ablation were included. In the ICM group, mean detected scar burden was higher than in the NICM group on LGE-CMR (total volume: 62.3±32.9g vs. 32.8±9.5g, p<0.001), using wall thinning model (WT)(mean scar area 69.0±45.6 cm2 vs. 23.4±23.6cm2, p=0.005) as well as LI (dense scar area: 39.2±28.1 cm2 vs. 11.0±6.3 cm2 , p=0.005). The absolute score difference per segment and patient between CCT and LGE-CMR was calculated and summed for all patients divided by the number of patients. Differences were more pronounced for NICM compared to ICM and LGE-CMR showed better concordance to LI than WT in both NICMP and ICM (Figure). Total procedure time was 205±68 min (ablation time 28±16 min; fluoroscopy time 15 ± 12 min). During a follow-up period of 19±7 months, 87 sustained VT episodes in 12 patients (33%) were documented. Three patients (8%) underwent a second VT ablation and one patient (3%) died during follow-up. In ICM, total scar volume on LGE-CMR and scar area on LI showed numerically higher predictive value for VT recurrence than total scar area by means of WT (AUC: LGE 0.76, LI 0.78 and WT 0.65 respectively), while in NICM scar characterization by means of WT yielded higher performance to predict VT recurrence than LI or LGE-CMR (AUC: LGE 0.67, LI 0.58, WT 0.83 respectively). Conclusions In patients undergoing VT ablation, both LGE-CMR and CCT are valuable for scar tissue characterization. Late iodine uptake on CCT showed a high concordance with LGE-CMR in both NICM and ICM.</scar<100%></scar<100%)>

The importance of scar border zone size in VT presentation and recurrence in post MI patients

Abstract Introduction Available mapping data in post-myocardial infarction patients describe ventricular tachycardia (VT) re-entry circuit characteristics of slow VT, that are typically related to transmural scars. Fast VTs with cycle lengths close to the refractory period may be related to functional re-entry in the scar border zone. Functional re-entry related border zone VTs may be difficult to control by ablation. Purpose The aims of this study are (1) to describe electroanatomical voltage map (EAVM) characteristics in post myocardial infarction (MI) patients with spontaneous and inducible fast VTs and (2) to assess the relation between scar border zone size and ablation outcomes. Methods Consecutive post-MI patients undergoing VT ablation at a tertiary referral center from January 2012 to November 2018 were included. Fast VT was defined as a VT cycle length (VTCL) = ventricular refractory period + max. 30ms. Areas of scar border zone (using 0.5 – 2.1mV/3.0mV cut-offs (according to LV remodeling stage; LVEF<47% and LV end-systolic volume index of >50 ml/m2)) were measured on the EAVM and correlated with clinical outcomes. Results In total, 138 patients were included (86% male; left ventricular ejection fraction 35±10%; 86% remodeled LV). Twenty-three patients (17%) had ≥1 fast VT (mean VTCL 275±52ms) at presentation, mean VTCL of the remaining patients 397±88ms). The median scar border zone size was 27% [IQR 20-38] of the left ventricular endocardial surface. Patients who presented with a spontaneous fast VT had a larger border zone than patients with slower VT (32% [IQR 28 – 41] vs. 25% [IQR 16 – 36], p=0.01). After ablation, 79 (57%) patients remained inducible for any VT, including 59/79 (75%) for a fast VT (median VTCL fast VT 260ms [IQR 236 -280]). Patients who remained inducible for fast VTs had a larger border zone than patients who remained inducible for slower VTs (35% [IQR 27 – 44] vs. 26% [IQR 20 – 36], p<0.001). During a median follow-up of 26 months [IQR 8 – 47], 45 patients (33%) had a VT recurrence (mean VTCL 357±98ms). Patients with a below median (27%) scar border zone area had a lower VT recurrence rate compared to patients with an above median scar border zone area (recurrence rate: 16/66 (24%) vs. 29/72 (40%), p=0.03). Kaplan-Meier survival analysis showed better free VT survival in the below median border zone patients (Log-rank: p<0.05) (Figure 1). Conclusion Patients who present with spontaneous fast VTs or who remain inducible for fast VTs after ablation have larger scar border zones during EAVM compared to patients with presenting or remaining slower VTs. A larger border zone appeared to be associated with higher VT-recurrence rates. The scar border zone may play an important role as VT substrate for (fast) VTs and may not be easily targeted by current ablation techniques.VT-free survival stratified by median BZ

Novel systematic processing of cardiac magnetic resonance imaging identifies target regions associated with infarct-related ventricular tachycardia

Abstract Introduction In the clinic, complete characterization of reentrant ventricular tachycardia (VT) circuits using classical electrophysiological criteria and state-of-the-art high density mapping during VT is complex, and often cannot be completed because of hemodynamic instability. This common limitation has motivated the implementation of mapping strategies during sinus rhythm or ventricular pacing aiming to identify scar regions associated with VT isthmuses or potential arrhythmogenicity. Complementary imaging-based strategies including advanced analyses of scar tissue characteristics have been also proposed for procedure planning and identification of potential arrhythmogenic regions. However, the most recent expert consensus report on catheter ablation of ventricular arrhythmia highlights the lack of agreement on the preferable signal intensity (SI) cut-off values for assessment of tissue heterogeneity and scar areas on late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) images. The latter makes LGE-CMR imaging processing highly operator-dependent and potentially sensitive to selection bias. Purpose We aimed at developing and validating a systematic processing approach on LGE-CMR images to identify potential VT corridors that may include protected isthmuses associated with VT maintenance. Methods Translational study including 18 pigs with established myocardial infarction and inducible VT undergoing in vivo characterization of the anatomical and functional myocardial substrate associated with VT maintenance. Clinical validation was conducted in a multicenter series of 33 patients with ischemic cardiomyopathy undergoing VT ablation. Three-dimensional CMR-LGE images were processed using systematic scanning of 15 signal intensity cut-off ranges to obtain surface visualization of all potential VT corridors. Analysis and comparisons of imaging and electrophysiological data were performed in individuals with full electrophysiological characterization of the isthmus sites of at least one VT morphology. Results In both the experimental pig model and patients undergoing VT ablation, all the electrophysiologically-defined isthmus sites (n=11 and n=19, respectively) showed overlapping regions with CMR-based potential VT corridors. Such imaging-based VT corridors were less specific than electrophysiologically-guided ablation lesions at functionally relevant isthmus sites (Figure). However, in patients, decreasing from 15 to 7 the number of signal intensity cut-off ranges for systematic imaging processing significantly reduced the area of imaging-based potential VT corridors, without diminishing the capability to detect functionally relevant VT isthmus sites. Conclusions Systematic processing of 3D LGE-CMR images provides unbiased identification of imaging based potential VT corridors that contain functionally relevant protected isthmus sites.

Single-beat mapping during programmed ventricular stimulation identifies infarct-related ventricular tachycardia isthmus sites

Abstract Introduction Complete characterization of reentrant ventricular tachycardia (VT) circuits using classical electrophysiological criteria and high-density mapping during VT is complex. Often, VT episodes cannot be fully characterized because of hemodynamic instability during the mapping procedure. This common limitation has motivated the implementation of mapping strategies during sinus rhythm or ventricular pacing aiming to identify scar regions associated with VT isthmuses or potential arrhythmogenicity. However, these strategies still require time-consuming catheter-based mapping. Purpose We aimed to develop and validate a single-beat mapping strategy during programmed ventricular stimulation (PVS) to identify scar regions associated with VT isthmus sites. We hypothesize that protected VT isthmuses within scar regions are characterized by larger activation time dispersion than surrounding scar areas not related to critical isthmus sites. Methods Experimental study including 16 pigs with established myocardial infarction (MI) in the anterior wall. Ten-to-twelve weeks after MI, pigs underwent left ventricular characterization using 3D late-gadolinium enhancement cardiac magnetic resonance imaging, and further invasive electroanatomical mapping to obtain high-density sequential activation maps during ventricular pacing and VT. High-density maps were compared with single-beat maps using a 64-pole basket catheter positioned in the left ventricle. After VT induction, high-density activation maps in well-tolerated VT episodes were used to identify VT isthmus sites. Simultaneous activation data from the 64-pole basket catheter were also obtained during PVS and VT. Off-line analysis was performed to: (i) validate single-beat activation maps during the baseline drive pacing cycle length (S1), and (ii) identify basket-catheter electrodes with the larger local activation time-dispersion score (LAT-DS) during PVS including up to 4 coupled extrastimuli (S2, S3, S4, S5) (Figure 1). LAT-DS was defined as the normalized product of the LAT of each electrode and the activation dispersion among its neighboring electrodes. Results Basket-catheter based single-beat activation maps during S1 pacing showed high correlation values with high-density sequential activation maps (N=16. R²=0.91). In 7 pigs, the VT isthmus site was fully characterized using high-density activation maps. During any of the coupled extrastimuli of the PVS protocol, basket catheter electrodes colocalizing with documented VT isthmus sites on high-density maps showed higher LAT-DS values compared to surrounding electrodes located on scar or healthy regions. Conversely, LAT values alone could not differentiate scar regions relevant for VT maintenance during PVS protocol (Figure 2). Conclusions Sixty-four pole single-beat activation maps during PVS identify left ventricular scar areas with higher than surrounding LAT-DS values that are associated with VT isthmus sites.Figure 1.Experimental modelFigure 2.A-Example. B-C-Full results

Use of cardiac MRI and wearable defibrillator to identify patients at low risk for arrhythmic events: single center experience

Abstract Introduction In our Center, patients (pts) with newly diagnosed HF and reduced LVEF underwent MRI to determine the presence and extension of delayed enhancement (DE) or scar areas. These patients were discharged with a wearable cardioverter defibrillator (WCD) as monitoring and temporary antiarrhythmic therapy until a three-month follow-up (FU). Subsequent FU was performed at 6 and 12 months. Methods From May 2016 to July 2023, 120 consecutive pts (97 M; mean age 65.3y±9.7y) with reduced EF (28.5%±8.5%) on OMT, were discharged with WCD and included in clinical FU. Coronary anatomy was acquired in 119 pts: absence of coronary atherosclerosis (ats) (44 pts); not significant ats(39 pts); Significant ats(36 pts). 1 pt did not perform angiography due to thyrotoxicosis. MRI was performed in 95 pts (EDV 181.9 ± 48.7 ml/m2; Mass 96.9± 23.4 g/m2, LVEF MRI 26.8% ±9.2). FU was performed at 3 months in all patients; at 6 months in 111pts and at 12 months in 107pts. WCD is still present in 4 pts. LGE score was used to quantify myocardial fibrosis by defining reduced extension as LGE score <5. Results MRI identified 57 pts with a delayed enhancement(DE) midwall pattern and in 13 of these there was a regional ischemic pattern also; 27 pts with regional scar; 18 pts without DE. During follow-up, 87 patients (75%) recovered LVEF function at 3 months (LVEF 44.3±6.3%) and were no longer indicated for ICD. 29 pts were implanted with ICD (25%). These patients had higher absolute and indexed volumes on MRI (p 0.053; p 0.042) and a greater presence of ischemic pattern (p 0.05). The LGE score was low in 76 pts (<5). A low LGE score is linked to the recovery of LVEF (p 0.04). Patients who undergo ICD had greater DE extension (p 0.01). 1 pt with a high LGE score (36.6) refused ICD and underwent SCD at 6 months. In pts with LGE score <5, 1 major arrhythmic event occurred (1 SVT in pt with ICD). In pts with LGE score >5, 3 major events occurred (1 shock on VF, 1 ATP on SVT, 1 SCD). 1 pt with extensive anterior akinesia who refused MRI presented 1 shock on VF at 6 months. 1 pt with partial recovery of LVEF and extensive anterior akinesia refused MRI and presented cardiac arrest for VF at 6 months. Conclusions MRI has become essential for risk stratification in patients with reduced LVEF. It is useful for identifying pts with severe impairment LVEF and low risk of events. The absence of DE and/or the presence of a low LGE score are linked to a low risk of arrhythmic events at 6 and 12 months and to a higher probability of recovery LVEF regardless of the etiology. The volumetric dimensions found on MRI are inversely linked to the recovery of LVEF. The WCD represents additional safety with excellent compliance in pts who still do not have clear indications for a definitive ICD. The combined MRI and WCD strategy can help to reduce the need for definitive ICD and therefore healthcare costs. The size of the sample does not allow definitive conclusions.

Predictors of decremental conduction after extrastimulus in post-infarction ventricular tachycardia substrate maps

Abstract Introduction Ventricular tachycardia (VT) substrate ablation techniques attempt to identify areas of decremental conduction (DC) within the scar, given their close relationship with VT isthmuses. DC identification requires the systematic use of extrastimuli during substrate mapping. This can be time consuming and induce ventricular arrhythmias during mapping. Objective This study aims to identify predictors of decremental response after extastimulus that allow recognizing areas with higher probability of DC conduction in order to focus functional mapping of the substrate on them. Methods Sixteen consecutive ischemic patients (93.8% male, 66.3±12.4 years) undergoing VT substrate ablation were included. A detailed substrate map during right ventricular (RV) pacing was obtained in all of them. Systematic analysis of electrograms (EGMs) recorded from the infarct area was performed during RV pacing at 600-500 ms, and during a short-coupled RV extrastimulus. Electrograms during RV pacing exhibiting decremental evoked conduction delay after an extrastimulus (DECD-AE) were compared to those not showing DECD-AE. Results Mean low voltage (<1.5 mV) area was 45±18.6 cm2. A total of 1744 EGMs were analyzed. Of them, 453 (26%) showed DECD-AE. Bipolar EGMs showing DECD-AE exhibited a higher number of deflections [4(interquartile range 3-5) vs 2(1-3); p<0.0001], a higher amplitude [0.52(0.27-1) vs 0.3(0.14-0.7) mV; p=0.003] and similar duration [114(102-135) vs 117(100-133 ms); p=0.492] compared to EGMs without DECD-AE. The area under curve was 0.64 for bipolar voltage and 0.8 for number of bipolar deflections. The presence of <3 bipolar deflections excluded DECD-AE with a negative predictive value of 98.5%. Conclusions In areas of myocardial scar, bipolar EGMs with <3 deflections are unlikely to present DECD-AE. Focusing functional mapping on signals with ≥3 deflections could simplify procedures and save time.

Impact of phase-correction of late-gadolinium enhancement images on quantification of scar metrics and in-silico VT-modelling in patients with an ischemic cardiomyopathy

Abstract Background Late gadolinium enhancement (LGE) is used to perform tissue characterization and has become the cornerstone to guide treatment of ventricular tachyarrhythmia (VT). Traditionally, LGE acquisition is reconstructed in two distinct forms: non-phase corrected magnitude (MIR) and phase-corrected inversion recovery (PSIR) images. However, the influence of MIR vs. PSIR on the quantification of scar metrics and the repercussion on estimating myocardial arrhythmogenicity have not been comprehensively explored. Aim This study investigated the influence of PSIR and MIR LGE on the quantification of scar metrics in a randomly selected cohort of patients with ischemic cardiomyopathy who had undergone imaging prior to ICD implantation and had received device therapy during follow-up. In addition, this study assessed how these image variations affect functional estimation of arrhythmogenicity using computational modelling. Methods ADAS 3D LV was used to generate scar maps from 2D PSIR and MIR LGE images in 10 patients. The extent of variation in scar-characteristics was evaluated by quantifying the borderzone (BZ), scar core, and conduction corridors. Electrical simulations were performed on the patient-specific anatomical models using the Virtual Induction and Treatment of Arrhythmias (VITA) framework. VITA was used to assess the electrical vulnerability of potential reentrant channels and provided the number of inducible VTs and their corresponding round-trip-time (RTT), an equivalent of VT cycle-length. Results Scar quantification using PSIR LGE resulted in a significantly larger BZ (22.1±23.7g vs. 6.2±2.7g, p <.001) and scar core (43.5±21.5g vs. 10.5±4g, p =.047). Furthermore, both the absolute number (6.8±4 vs. 3.4±1.5, p = .031) and weight (13±13.1g vs. 1.4±0.8g, p =.018) of conduction corridors were also higher using PSIR. VTs were inducible in 8 PSIR-models and 7 MIR-models. Despite large differences in scar characteristics, VITA metrics were not significantly different between PSIR and MIR derived models. Although, the absolute number of inducible VTs were larger for PSIR (6.2±5.4 vs. 3.4±3.1), non-parametric testing using Wilcoxon signed-rank test did not demonstrate a significant difference (Z = -1.334, p =.139). A comparable, non-significant difference was observed for mean- (117±78 vs. 79±60, p =.257) and max-RTT (181±141 vs. 120±103, p =.294) between PSIR and MIR derived models. Conclusion PSIR resulted in significantly larger BZ, scar core area, and conduction corridors. While the absolute, VITA-derived estimation of myocardial arrhythmogenicity, including inducible VTs and RTT, were higher in the PSIR-based quantification, these differences did not reach statistical significance. These results highlight important differences between two clinically applied image reconstruction techniques for the assessment of arrhythmogenic substrate, emphasizing the need for additional investigation and refinement of scar quantification techniques.

Ventricular tachycardia mapping and ablation using MIXture of well-established approaches. The MIX-VT study

Abstract Introduction Ablation for ventricular tachycardia (VT) is still challenging despite impressive technology development, especially in mid- or low-volume centers. The most frequently used approach is homogenization of scar area responsible for VT, combined with standard electrophysiological (EP) approaches such as VT inducibility and mapping. However, in real life long-term efficacy of VT ablation in such centers does not exceed 50%. We hypothesized that an approach consisting of the mixture of various well-established parameters would be more effective than scar homogenization and VT non-inducibility as the endpoints. Purpose To compare the outcome of VT ablation using the standard approach (scar homogenization) and a more complex approach, called the MIX-VT protocol, using late potential mapping + pace mapping with rapid change of VT morphology to localize the critical isthmus + core isolation. All procedures were performed using the 3D mapping system, Pentaray mapping catheter, Smart-Touch ablation catheter and intracardiac echocardiography (ICE). Methods 48 consecutive patients (41 male, mean age 71.5 years) with ischemic cardiopathy referred for urgent VT ablation were included: 23 patients underwent "standard" VT ablation between December 2018 and December 2019, whereas the next 25 patients underwent ablation using the MIX-VT protocol between January 2020 and December 2020. First step in the MIX-VT group was to perform ICE imaging of the scar area from the right ventricle. Next, left ventricular maps were created during rhythm at which spontaneous VT occurred (sinus or paced). Areas of late potentials were identified to localize the critical isthmus where the abrupt change in the paced-QRS axis was seen. Finally, areas delineated by these two above-mentioned maneuvers where ablated in order to achieve core isolation (Figure 1). The patients were followed for 12 months in the outpatient clinic during ICD examination. The composite end-point for follow-up was VT recurrences terminated by anty-tachycardia pacing (ATP) or shock, or death. Results Clinical and demographic variables were similar between the two groups (Figure 2), except for a higher prevalence of diabetes mellites and number of previous ablations in the standard group (4/25 [16%] vs 10/23 [43%], p=0.03 and 2/24 vs 8/23 [34.8], p=0.03, respectively). Three patients from the MixVT group and one patient from the standard group were lost to follow-up. During follow-up, VT recurrences were significantly less frequent in the MIX-VT group (3/22 [13.6] vs 10/22 [45.4]. p=0.02. It was mostly driven by less ATP therapy. (Figure 2). One patient from the standard approach groups died. Conclusion Ablation for VT in low- or medium volume centers using the combination of well-established various EP approaches resulted in the improvement in overall survival and arrythmia-free survival. The presented approach does not involve additional resource utilization.

Vein of Marshall ethanol infusion related lesion durability. A randomized dual centre pilot study

Abstract Introduction Vein of Marshall ethanol infusion (VOM-EI) creates a local ablation which includes epicardial bridges, AF triggers, vein innervation and facilitates mitral isthmus (MI) ablation. Recent trials demonstrated that in persistent AF patients the addition of VOM-EI to RF catheter ablation (CA) increased success rate vs CA alone. Moreover, a novel CA strategy (VOM-EI, PVI, and specific linear lesions set) is associated with a high rate of freedom from AF. Nevertheless, in these studies VOM-EI and RFCA were performed as different step of the same procedure. We hypothesize that performing electro-anatomical mapping (EAM) right after the VOM-EI would lead to an overestimation of ethanol-induced scar because of a certain amount of reversible oedema. This could affect the durability of the lesion set and possibly the success rate. Aim We postulated that VOM-EI performed at least 1 month earlier than RFCA would show a significantly smaller EAM low voltage area as compared to the standard strategy. Methods Patients with recurrent persistent AF with no history of previous ablation were enrolled in this randomized, dual centre, pilot study. All included patients were randomized 1:1 to group 1 (experimental): VOM-EI and after at least one month later high-definition (HD)-EAM and RFCA (PVI, MI, LA dome, cavo-tricuspid isthmus). group 2 (control): to a standard procedure (VOM-EI then 5 minute later HD-EAM and RFCA). Primary endpoint was ethanol induced HD-EAM scar area. According to the endpoint patients with unsuccessful VOM-EI were excluded. Moreover patiets with or no branches morphology, VOM dissection, and mechanical leakage were also excluded because these are demonstrated to be related to a smaller VOM-EI related lesion. Clinical and procedure related data were also collected. Results Forty consecutive patients met the inclusion criteria. The two groups did not differ for baseline characteristics (see table 1). Mean ethanol-induced HD-EAM scar area was significantly smaller in 20 patients where VOM-EI was performed at least 1 month earlier as compared to the standard procedure group (2,5±2,4 vs 11,2±9,5 cm2, p=0,018). The set of linear lesions was successful achieved in all patients. Notably the two group did not differ for any procedural technical aspect of mitral isthmus block (table 1). Neither VOM-EI nor AF ablation procedure related complications were recorded. Conclusion This is the fist randomized pilot study to demonstrate that a consistent amount of ethanol-induced related lesion could be reversible at least in its endocardial aspect of the left atrium. This would possibly affect the long-term stability of the lesion set. Notably, we still had a high rate of block at first mitral line attempt which could possibly be related to a persistent effect of VEOM-EI on the epicardial aspect of the left atrium. Larger population, randomized trial is needed to confirm this preliminary result and if it would affect the procedure success.Table 1Picture 1

Termination without global capture: electrocardiographic and anatomical characteristics using 3D-electroanatomical mapping system in reentrant ventricular tachycardia

Abstract Background Termination without global capture (TWGC) is the phenomenon which a pacing stimulus applied during ventricular tachycardia (VT) terminates the tachycardia without generating a QRS complex, and is considered as an indicator for the critical component of the circuit. The details of the electrocardiographic and anatomical characteristics of the site using a 3D-electroanatomical mapping system (3D-EAM) remain unknown. Purpose This study aimed to retrospectively analyze the cases that showed TWGC during VT mapping and ablation, and to investigate the electrocardiographic characteristics and relationship with the substrate identified by 3D-EAM. Methods Of 632 cases of VT associated with structural heart disease from July, 2019 to July, 2023 at a university hospital and a university medical center, cases with TWGC were analyzed. Results TWGC was observed in 10 patients (median age 61 years, 9 males, 5 ischemic cardiomyopathy, median LVEF 31%) at least once (12 times) in 11 locations. Local capture was observed in 6. The QRS morphology generated by continued pacing after TWGC matched the clinical VT in only 5 VTs (42%). Five showed decremental conduction of stimulus to QRS interval following the TWGC. In 11 locations, 4 corresponded to scar area (<0.1 mV) in the voltage map, 6 to border zone (0.1-1.5 mV), and 1 had no information on 3D-EAM. Of 12 times of TWGC, 3 were at the entrance, 1 at the central isthmus, and 1 at the exit. Acute elimination of clinical VT was successful in 7 of 10. Conclusions More than half of the sites with TWGC were located at the border zone in 3D-EAM. TWGC also occurred in the central or exit area, and local capture was observed frequently.Termination without global capture

Clinical validation of a novel digital twin framework for ventricular functional substrate simulation in post-infarction patients

Abstract Background Catheter ablation is a cornerstone treatment for scar related post-infarction ventricular arrhythmias. Functional substrate driven ablation strategies guided by local activation time (LAT) mapping have been proven as efficient and effective approaches, especially when dealing with large scar areas. In-silico electrophysiological modeling is emerging as a potential tool for procedural planning and guidance. Purpose To clinically validate the feasibility, diagnostic performance, and accuracy of a novel late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) based digital twin framework for simulated LAT map generation in post-infarction patients and their integration with CARTO3 EAM suite. Methods Five ischemic subjects who underwent CMR-aided scar-related ventricular tachycardia ablation at our referral center were retrospectively enrolled. Their CMR derived 3D pixel-signal-intensity (PSI) maps generated with ADAS3D were processed with novel in-house software to obtain patient-specific ventricular geometry, tissue characterization, and to generate a model of Purkinje system and myocyte fiber orientation. According to local normalized pixel intensity (NPI) values, myocardial regions were marked as healthy, scar, or border-zone. Electrophysiological properties of border-zone (BZ) were modulated according to local NPI. Continuous and 8-steps isochronal endo-epicardial LAT maps were generated and imported in CARTO3 system, aligned with electroanatomical mapping (EAM), and compared at an ASE 17-segments level, in terms of sensitivity, specificity, predictive values, and accuracy to actual high-density LAT maps obtained with a multipolar catheter. Deceleration Zones (DZ) were defined as previously described (>3 isochrones within 1 cm radius). Results A total of 85 ASE segments (34 epicardial) were analyzed. 24 EAM segments (28%) held DZs, 40 (47%) segments harbored bipolar scar or BZ. Thirty-seven (44%) CMR segments held scar core/BZ. Thirty (35%) digital model segments harbored DZs. Generated LAT maps were successfully imported and aligned with CARTO3 EAM suite for validation. In terms of DZ localization prediction, our LAT model showed 83% sensitivity (95% CI 63%-95%), 90% specificity (95% CI 80%-96%), 77% positive predictive value (PPV) (95% CI 56%-91%), 93% negative predictive value (NPV) (95% CI 83%-98%), 88% accuracy (95% CI 79%-94%). Conclusion Our newly developed framework for LGE-CMR derived functional substrate simulation in post-infarction patients holds high sensitivity, specificity, predictive values, and accuracy for DZ localization. Further validation, with a larger sample size, is required for evaluating potential implications in clinical practice.

Efficacy of laser balloon left atrial roof ablation for patients with atrial fibrillation

Abstract Background The roof area ablation beyond pulmonary vein (PV) isolation (PVI) using a cryoballoon has been described as an effective therapy for patients with atrial fibrillation (AF). However, the effect of roof area ablation performed with a visually guided laser balloon (VGLB) remains to be elucidated. Purpose This study aims to investigate the efficacy of roof area ablation using VGLB. Methods A total of 325 patients with AF (paroxysmal AF=199, persistent AF=126) who underwent VGLB ablation from July 2018 to May 2022 were analyzed retrospectively. After initial circular isolation, VGLB was inflated to a larger size on both sides of superior PVs, and the isolation areas were extended to the roof portion. At the end of the procedure, left atrial (LA) voltage mapping was obtained to assess the LA roof scar area, and differential pacing was performed to confirm the complete conduction block. Our study population was divided into the PVI group (LB-PVI, n=228) and the roof line block beyond PVI group (LB-Roof, n=97). The efficacy endpoint was defined as freedom from atrial tachyarrhythmia (ATa) between months 3 and 12. Results One-year clinical follow-up could be obtained in 170 patients with LB-PVI and 81 patients with LB-Roof. The Kaplan-Meier survival curves are shown in Figure. At the end of the 12 months of follow-up, freedom from ATa was 80.8% in patients with LB-PVI and 91.2% in LB-Roof. The ATa freedom rate was significantly higher in the LB-Roof than in the LB-PVI (P=0.03). Conclusion The roof area ablation using VGLB was proved to be effective for patients with AF.The Kaplan-Meier survival curves

#2305 Mice with a PAX2 missense variant are susceptible to experimental focal segmental glomerulosclerosis (FSGS) and display impaired glomerular repair

Abstract Background and Aims Focal segmental glomerulosclerosis (FSGS) is a histopathologic lesion observed in chronic kidney disease characterized by scarring of the glomerulus due to the injury and irreversible loss of highly specialized glomerular epithelial cells called podocytes. Recent studies suggest that podocytes may be regenerated by another population of glomerular epithelial cells called parietal epithelial cells (PECs), although this remains controversial. PAX2 is a transcription factor protein that regulates glomerular development and its expression persists in adult parietal epithelial cells (PECs), postulated to serve as a reservoir for podocytes in the event of injury and loss. Our team previously found that PAX2 pathogenic missense variants account for 4% of adult FSGS. In our present study, our aim is to determine whether PEC-mediated podocyte regeneration is impaired in mice with a pathogenic Pax2 missense variant (Pax2-MV). Method FSGS was induced in wildtype and Pax2-MV mice using Adriamycin. Urine samples were collected from mice every week for 28 days to measure proteinuria. At 28 days after Adriamycin injury, kidneys were collected for histopathology, transmission electron microscopy, and immunofluorescence staining for PAX2 and podocyte marker WT-1. Glomeruli from Adriamycin-injured mice were also isolated through intra-cardiac perfusion with Dynabeads and subjected to mass-spectrometry for proteomics analysis. Proteins with statistically-significant fold changes in expression levels were further analyzed by Gene Ontology to determine biological and molecular processes involved in pathogenesis. Kidney tissue from an FSGS patient with a pathogenic PAX2 missense variant was also examined by histopathology and PAX2 immunohistochemistry. Results Compared to wildtype, Pax2-MV mice were more susceptible to worsened FSGS after Adriamycin, as demonstrated by worsened glomerular scarring, increased podocyte injury and loss, and increased proteinuria, associated with increased morality in Pax2-MV mice (Fig. 1A-B). Wildtype mice showed fewer PAX2-expressing PECs after injury, accompanied by the occurrence of PAX2/WT-1 co-expressing glomerular tuft cells (Fig. 2A-B). These suggest that in Adriamycin-injured wildtype, PAX2-expressing PECs move to the glomerular tuft, where they trans-differentiate to a podocyte fate. In contrast, Pax2-MV mice showed no changes in numbers of PAX2-expressing PECs after injury, associated with fewer PAX2/WT-1 co-expressing glomerular tuft cells compared to injured wildtype (Fig. 2A-B). These suggest that in Adriamycin-injured Pax2-MV mice, PAX2-expressing PECs are unable to move to the glomerular tuft, resulting in decreased numbers of cells undergoing podocyte trans-differentiation. A subset of ectopic PAX2-expressing glomerular tuft cells after injury was increased in Pax2-MV mice (Fig. 2A), suggesting a pathologic process given the worse outcomes observed in these mice. Consistent with findings from injured Pax2-MV mice, we found that in an FSGS patient with a pathogenic PAX2 missense variant, PAX2-expressing glomerular tuft cells overlap with areas of glomerular scarring, while in a normal human kidney biopsy, PAX2 expression is only observed in PECs but not within glomerular tuft cells (Fig. 2A). Lastly, proteomics Gene Ontology analysis of isolated glomeruli demonstrated biological and molecular processes indicative of maladaptive glomerular repair in injured Pax2-MV mice, including decreased regulation of cell shape, decreased cell-cell junction assembly and decreased actin and cadherin binding compared to wildtype (Fig. 2C). Conclusion Altogether, our findings suggest that PAX2-expressing PECs migrate to the glomerular tuft to assist in podocyte regeneration in wildtype. However, this mechanism is impaired in Pax2-MV mice, leading to worsened podocyte loss and injury and further exacerbation of glomerular disease (Fig. 2C). Our findings provide a further understanding of normal and impaired regeneration mechanisms in FSGS, and our identified pathogenic mechanisms can be further harnessed for future therapeutic development.

#2069 Elucidating the function of novel Arg1+/Clec4d+ scar-associated monocyte-derived macrophage population in driving fibrosis in kidney disease models

Abstract Background and Aims Fibrosis is the final common pathway in all progressive kidney disease. Macrophages are a major myeloid cell component of the renal mononuclear phagocyte system, with roles in defence against infection, renal injury, and repair. Using single-cell RNA sequencing, we identified a novel myeloid cell subset exclusively present in acute injury of the unilateral ureteric obstruction (UUO) model of kidney fibrosis. This population transcriptomically aligns to monocytes but is enriched for both Arginase-1 (Arg1) and the C-type lectin 4d (Clec4d) and a large number of pro-inflammatory and pro-fibrotic genes. We hypothesise that this novel Arg1+/Clec4d+ population contributes to fibrosis deposition in progressive kidney disease. Methods Monocyte-macrophage populations were characterised in different pre-clinical models; UUO, unilateral ischaemic reperfusion injury (uIRI) and subtotal nephrectomy with flow cytometry. Arg1+/Clec4d+ cells were identified by RT-qPCR, flow cytometry, and immunofluorescence. The origin and consequence of Arg1 deletion in monocytes on renal fibrosis was determined by utilising Ccr2-ERT2-TdTomato and Ccr2-ERT2-TdTomato; Arg1 fl/fl mice, respectively. Results The presence of the Arg1+/Clec4d+ cells was validated in the UUO, uIRI and subtotal nephrectomy models of kidney injury. Analysis of intra-renal inflammation revealed CD45+CD11b+Arg1+ cells persisted and increased in number across 7 days. Post-injury, Arg1+ cells were confirmed to be Clec4dhi. To confirm that Arg1+/Clec4d+ cells were derived from monocytes (Ccr2+), we administered tamoxifen to Ccr2CreERT2-TdTomato mice under a single or multiple-dose regimen following UUO surgery. At day 7 post-injury, ∼50% and ∼90% of the Arg1+ cells were TdTomato+ following a single or multiple doses of tamoxifen, respectively, suggesting that these cells are primarily monocyte derived. Moreover, the Arg1+/Clec4d+ cells were found to localise to areas of scarring (Fig. 1). To investigate the therapeutic potential of targeting Clec4d+ expressed on the Arg1+/Clec4d+ macrophages, mice underwent UUO surgery and given multiple doses of a Clec4d-neutralising antibody. A decrease in Arg1 and fibrosis-related gene expression was evident by day 7 post-injury. To understand the role of increased Arg1 expression in the cells we generated Ccr2-ERT2-TdTomato; Arg1 fl/fl mice. These mice had as expected a reduced Arg1 expression in the Ccr2+ population and metabolic profiling by SCENITH of the tissue monocytes revealed that the loss of Arg1 in the cells reduced their glucose dependence. The loss of Arg1 in these cells reduced Havcr1 gene expression in the kidney. Conclusion As fibrosis is a pathological process that can affect any organ, the work included here, in addition to the proposed future studies, has the potential to develop novel therapeutics that limit fibrosis and enhance repair to halt the progression of disease in CKD.

Testosterone promotes nerve tethering and acellular biomaterial perineural fibrosis in a rat wound repair model.

Nerve scarring after traumatic or iatrogenic exposure can lead to impaired function and pain. Nerve-adjacent biomaterials promoting a regenerative tissue response may help reduce perineural fibrosis. Our prior work suggests testosterone may promote fibrotic skin scarring, but it is unknown how testosterone alters nerve fibrosis or shifts the response to biomaterials. Sterilized Lewis rats received either testosterone cypionate (+T) or placebo (-T) biweekly. Fifteen days later, wounds were created over the sciatic nerve and covered with acellular extracellular matrix (AM) or closed primarily (PC). At day 42, force gauge testing measured the force required to mobilize the nerve and wound tissue was analyzed. Nerve mobilization force was greater in +T vs -T wounds (p<0.01). Nerves tore before gliding in 60% of +T vs 6% of -T rats. Epidermal gap (p<0.01), scar width (p<0.01), and cross-sectional scar tissue area (p=0.02) were greater in +T vs -T rats. -T vs +T rats expressed more Col-3 (p=0.02) and CD68 (p=0.02). Nerve mobilization force trended non-significantly higher for PC versus AM wounds and for +T versus -T wounds within the AM cohort. Testosterone increases nerve tethering in the wound healing milieu, altering repair and immune cell balances. Testosterone significantly increases the force required to mobilize nerves in wound beds and elevates histologic markers of scarring, suggesting that testosterone-induced inflammation may increase perineural adhesion. Testosterone may reduce the potential anti-tethering protective effect of AM. Androgen receptor antagonism may represent a therapeutic target to reduce scar-related nerve morbidity.

A Comparative Analysis of Quality of Life in Children Managed for Omphalocele and Gastroschisis.

Evaluation of quality of life (QoL) in paediatric surgical patients has not always received enough attention in the past. Our aim was to follow up patients with abdominal wall defects for a decade and (1) to analyse children's view on QoL and to analyse parent's view on QoL, (2) to evaluate satisfaction and psychological problems, (3) to assess present complaints including subjective aspects such as food intake, reduced appetite, pain in scar area and general abdominal pain and (4) verifiable clinical symptoms assessed through a physical examination and ultrasound. It was hypothesised that QoL would differ from gastroschisis (GS) and omphalocele (OC) children depending on the type of abdominal wall defect. A retrospective case-control design was used to compare children with GS (n = 36) and OC (n = 18). A clinical examination, including abdominal inspection, palpation and auscultation of bowel sounds with abdominal ultrasound, was offered, combined with a structured interview and specific QoL questionnaire (KINDL®). The focus was on QoL, child development, present complaints and satisfaction with the cosmetic outcome. During clinical examinations with ultrasound, GS children were significantly more likely to have bowel loops stuck at the scar area (P = 0.008) with bowel malrotation and abnormal appendix position, compared to OC children (P = 0.037). They were significantly more likely to report irregular stools (P = 0.02) but were satisfied with the cosmetic outcome of the abdominal skin scar in 81% of cases. The KINDL® evaluation showed in the dimensions of QoL, namely 'body awareness', 'mental health', 'self-esteem', 'family', 'friends' and 'school', that there were no significant differences to healthy children. OC/GS parents were satisfied with their children's physical development and QoL, noting no limitations in normal daily activities. Parents of OC children reported suffering from OC/GS-associated problems (P = 0.028) at the time point of interview. Subjective QoL did not differ significantly between OC and GS children. The satisfaction with the cosmetic outcome of the abdominal skin scar was good. On ultrasound examination, adherent bowel loops and bowel malrotation with resulting stool irregularities affect GS children. OC children's parents reported suffering from OC/OS-associated problems, and all parents need to be educated about the symptoms of recurrent sub-ileus events or atypical appendicitis.

Interval training suppresses nod-like receptor protein 3 inflammasome activation to improve cardiac function in myocardial infarction rats by hindering the activation of the transforming growth factor-β1 pathway

ObjectiveMyocardial infarction (MI) -induced cardiac dysfunction can be attenuated by aerobic exercises. This study explored the mechanism of interval training (IT) regulating cardiac function in MI rats, providing some theoretical basis for clarifying MI pathogenesis and new ideas for clinically treating MI.MethodsRats were subjected to MI modeling, IT intervention, and treatments of the Transforming growth factor-β1 (TGF-β1) pathway or the nod-like receptor protein 3 (NLRP3) activators. Cardiac function and hemodynamic indicator alterations were observed. Myocardial pathological damage and fibrosis, reactive oxygen species (ROS) level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities, MDA content, inflammasome-associated protein levels, and inflammatory factor levels were assessed. The binding between TGF-β1 and receptor was detected.ResultsMI rats exhibited decreased left ventricle ejection fraction (LVEF), left ventricle fractional shortening (LVFS), left ventricular systolic pressure (LVSP), positive and negative derivates max/min (dP/dt max/min) and increased left ventricular end-systolic pressure (LVEDP), a large number of scar areas in myocardium, disordered cell arrangement and extensive fibrotic lesions, increased TGF-β1 and receptor binding, elevated ROS level and MDA content and weakened SOD, CAT and GSH-Px activities, and up-regulated NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC) and cleaved-caspase-1 levels, while IT intervention caused ameliorated cardiac function. IT inactivated the TGF-β1 pathway to decrease oxidative stress in myocardial tissues of MI rats and inhibit NLRP3 inflammasome activation. Activating NLRP3 partially reversed IT-mediated improvement on cardiac function in MI rats.ConclusionIT diminished oxidative stress in myocardial tissues and suppressed NLRP3 inflammasome activation via inactivating the TGF-β1 pathway, thus improving the cardiac function of MI rats.

Effects of early debridement and conservative eschar removal followed by wound coverage with acellular dermal matrix in the treatment of children with deep burns

Effects of early debridement and conservative eschar removal followed by wound coverage with acellular dermal matrix in the treatment of children with deep burns