Inducible Ventricular Tachycardia Research Articles

Induction of fast ventricular tachycardia by aCRT-D device: what is the mechanism?

Induction of fast ventricular tachycardia by aCRT-D device: what is the mechanism?

Systematic right ventricular electrophysiologic evaluation in patients with repaired tetralogy of Fallot before pulmonary valve replacement

Abstract Introduction Adults with repaired tetralogy of Fallot (rToF) are prone to develop ventricular tachycardia (VT) in adulthood, due to reentry related to slowly conducting anatomical isthmuses (SCAI). Pulmonary valve replacement (PVR) in patients without history of VT, may lead to obliteration of unrecognized SCAI with subsequent catheter ablation failure; electrophysiologic study is thus recommended before PVR. A systematic evaluation of the topology of SCAI in this population is, however, scant. Methods Consecutive rToF patients undergoing PVR with native right ventricular outflow tract were studied with pre-PVR EPS. Electroanatomical mapping with systematic evaluation of all possible anatomical isthmuses (AI) with pacemapping, activation mapping in sinus/paced rhythm and bipolar voltage mapping was performed (AI1: anterior scar/patch to tricuspid annulus; AI2: anterior scar to pulmonary annulus; AI3: pulmonary annulus to ventricular septal defect – VSD- patch; AI4: VSD to tricuspid annulus). Conduction velocity (CV) across all documented AI was calculated (ratio between the distance among the nearest point with bipolar voltage >1.5 mV and their difference in activation timing). Ventricular programmed stimulation was performed at 2 sites (apex and outflow tract) with drive train ad 600/400 ms, up to three extrastimuli until refractoriness or induction, during baseline and isoproterenol infusion. Radiofrequency catheter ablation (RFCA) was performed in all patients with inducible VT and/or SCAI, aiming at conduction block across the SCAI validated with differential pacing. Results Between May 2023 and November 2023, 10 patients with rToF and 1 double outlet right ventricle were studied (73% males, age 46±10 years; 54% with a previous shunt, 46% with a previous transannular patch, 27% pulmonary valvotomy and infundibular boring; median age at surgery 4 years, interquartile range 3-6). EPS was positive for inducible VT in 4 patients (mean cycle length 297 ms, 3 with left bundle branch morphology and 1 right bundle branch morphology, all inferior axis) and polymorphic VT in 1. AI1 was present in 5 patients, AI2 in 5, AI3 in 7, AI 4 in 2. At least 1 SCAI was present in 7 patients (64%), 2 SCAI in 3 patients (43% of patients with SCAI; in every patient SCAI3+SCAI2 in 2 and SCAI 4 in 1 patient). There were no SCAI1; there were 3 SCAI 2 (mean CV 0.43 m/s), 4 SCAI 3 (mean CV 0.3 m/s), 1 SCAI 4 (CV 0.4 m/s). RFCA was performed in 8 patients; acute success was achieved in all patients, achieving bidirectional conduction block across treated SCAI and non-inducibility of VT. Conclusions SCAI are often present in rToF candidate to PVR and without clinical history of spontaneous VT, involving prevalently SCAI3 and SCAI2. Inducible VT is not sufficient as a marker of arrhythmic risk and SCAI should be better sought for. RFCA of SCAI with bidirectional conduction block is acutely highly efficacious.

First experiences with protected VT ablation using surgical Impella 5.5

Abstract Introduction Ablation of ventricular arrhythmias (VA) is still challenging due to the complex substrate of the underlying heart disease. Depending on specific risk factors acute hemodynamic decompensation during or after VT ablation procedures may occur and hemodynamic support may be required. Protected VA ablation with different devices has been evaluated but associated complications like bleeding, vascular closure or weaning from the device have been restrictive. We present data on a dedicated approach to patients with anticipated hemodynamic deterioration using preventive surgical Impella support. Method 5 patients (2 female) underwent protected VT ablation under our standardized protocol. Indication for Impella support was severely impaired left ventricular function and multiple medical therapy refractory ventricular arrhythmias. 4 patients had conventional VT ablation before. Mean age was 66,8 years, mean CHADSVASC 4,4, 1 patient with non-ischemic cardiomyopathy (CMP), 1 with hypertrophic non-obstructive CMP, 3 patients with ischemic CMP. Mean EF was 20%, mean mixed venous saturation was 36 %, mean PAINESD score 27. In all patients a 5.5. Impella was implanted surgically 1 day before planned VT ablation via the right subclavian artery. VT ablation procedure started with substrate mapping, VT induction and activation mapping of the inducible VT to identify the critical VT isthmus. Ablation was directed to dissection of the critical isthmus of inducible VAs and elimination of all late potentials within low voltage areas. The Impella device was explanted after weaning off the hemodynamic support. Results Implantation of Impella 5.5 was successfully performed in all patients in general anesthesia without any complication via surgical approach. Specifically, no access site vascular complications were noted. In 4 patients the VT ablation procedure was performed in analgosedation, 1 patient in GA as this patient was intubated due to recurrent VA requiring defibrillation. Mean procedure time was 125 min, radiation time 1,3 min, inducible VTs 1,3 , median 2 morphologies. In all patients all inducible VTs could be eliminated, in 1 patient polymorphic VA was still inducible at the end of the procedure. Impella was explanted after mean 5,2 days (3-11 days). No complications occurred. All patients were discharged alive on heart failure medication and in 2 patients with amiodaron. At a mean follow up of 3.5 months, all patients are alive without VA recurrence and heart failure decompensation. Conclusion Surgical Impella implantation for protected VT ablation in severe heart failure patients is feasible and allows for effective VT mapping and ablation. Access site safety and protection for heart failure decompensation in addition to the possibility of individually mobilisation and weaning after the procedure make this protocol an attractive option. Prospective evaluation of standardized indication is needed.

Senolysis ameliorates increased susceptibility to ventricular arrhythmias in prediabetes

Abstract Background Obesity and associated prediabetes are major risk factors for cardiovascular disease that promote cellular senescence and predispose to ventricular arrhythmias (VA). In consequence, targeting cellular senescence may represent a feasible therapeutical approach that can decrease VA susceptibility in aged hearts. The aim of the present study was to characterize the impact of senolysis on glucose control, left ventricular function (LVF) and VA susceptibility in a prediabetic mouse model. Methods Ten – 12 week-old C57Bl/6J mice were fed a high-fat diet over a period of 12 weeks to generate diet-induced-obesity (DIO). Afterwards, mice were treated with dasatinib (5 mg/kg) and quercetin (50 mg/kg) (DQ) or vehicle (10 % DMSO) by oral gavage three times in 7 days. Cardiac senescence was assessed by measuring Cdkn1a mRNA expression levels. Glucose control was monitored by glucose tolerance testing. LVF was evaluated by echocardiography and myocardial contractility was assessed by sarcomere length measurements in paced single cardiomyocytes. VA susceptibility testing was performed by programmed ventricle stimulation combined with an epicardial fluorescence imaging of the LV anterior wall in isolated hearts. VA susceptibility was quantified by an established scoring system. Results Cardiac senescence, as assessed by expression of Cdkn1a mRNA (encoding p21), was increased in DIO mice (P=0.0004, Figure 1A), whereas DQ reduced cardiac senescence (P<0.0001, Figure 1A). Glucose control was impaired in DIO mice (P<0.0001) and could be partially restored by DQ (P=0.003). LVF was ameliorated by DQ in DIO mice (P=0.018). In agreement, contractility in single cardiomyocytes was improved (Amplitude of sarcomere contraction: P=0.0003, figure 1B; speed of sarcomere contraction: P=0.046). VA susceptibility was increased in DIO mice (number of inducible VAs: P=0.001, figure 1C; VA score: P=0.0002; VT inducibility: P=0.001) whereas DQ limited VA susceptibility (number of induced VAs: P=0.004, Figure 1C; VA score: P=0.004; VT inducibility: P=0.025) in isolated hearts. Conclusions Our findings demonstrate that senolysis ameliorates glucose tolerance and LVF while reducing VA susceptibility in obesity and prediabetes. In consequence, senolysis may offer a perspective therapeutical approach for obese patients at risk for VAs. Further experiments will address underlying molecular mechanisms to identify potential therapeutical targets.

Renal denervation for the management of refractory ventricular arrhythmias

Abstract Background While catheter ablation (CA) has proven effective in managing ventricular arrhythmias (VA) associated with structural heart disease, a portion of patients continue to experience refractory VA despite medical treatment and multiple CA procedures. In such cases, additional techniques, such as autonomic neuromodulation, have been explored. Renal denervation (RDN), traditionally performed for the treatment of resistant arterial hypertension, inhibits the afferent renal sympathetic pathway, leading to reduced efferent sympathetic overactivation on a systemic level. Due to this mechanism, it has also been studied for the management of arrhythmias, including atrial fibrillation and VA, with favorable results. Objective To assess the effectiveness and safety of RDN for the management of refractory VA storms in high-risk patients. Methods A retrospective analysis of RDN procedures for electrical storms, conducted at a tertiary center between February 2020 and September 2023. We analyzed baseline patient characteristics, procedural details, and acute complications. Recurrence of VA after RDN was assessed at one and six months. Results A total of 7 patients underwent RDN for the treatment of refractory VA. The mean age was 56 ± 10 years (6 male). The primary diagnosis was ischemic cardiomyopathy (n=5), with a mean left ventricular ejection fraction (LVEF) of 20 ± 5%, and no history of resistant arterial hypertension. All patients had an implantable cardioverter-defibrillator (ICD) (two with concomitant resynchronization therapy). Five patients had undergone previous endocardial VA ablation. Of the two patients without prior VA ablation, one had a contraindication because of a large left ventricle thrombus, and the other was submitted to an electrophysiological study, but without inducible ventricular tachycardia. In the four weeks before RDN, patients exhibited a mean of 12 ± 18 sustained VA episodes, meeting the criteria for electrical storm (3 ≥ episodes in 24h). During the procedure, there was a mean of 7 ± 8 radiofrequency applications in the right renal artery and 6 ± 10 in the left renal artery. No acute complications were observed. One month after the procedure, VA episodes were reduced to a mean of 0 ± 1, with only two patients experiencing recurrent VA. After six months, the absence of VA recurrence remained consistent, with only one patient experiencing new episodes. There were no deaths during this period. Conclusion In our pilot study, RDN appeared to be a safe and effective treatment for the management of VA.VA episodes before and after RDN

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

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.

Ablation of hemodynamically unstable ventricular tachycardia guided by ultra-high density pacemapping and PASO correlation map, a multi-center clinical trial

Abstract Background Due to hemodynamic instability during ventricular tachycardia (VT), obtaining a complete electroanatomic map is often difficult if not impossible. Pace-mapping has progressed but still lacks precision and may not reveal sufficient details for complete ablation of the potential critical isthmus. Purpose We hypothesized that a novel strategy of combining ultra-high density (HD) pace-mapping using the PASO algorithm and Carto system to match the induced/clinical VT may aid in the reconstruction of the VT critical isthmus and effective VT ablation leading to reduce the risks of VT recurrence. Methods This was a prospective, multi-center trial conducted between January 2021 and July 2023. We enrolled 30 patients with ischemic heart disease and scar mediated recurrent VT clinically indicated for ablation. Following induction of clinical VT, we performed ultra-HD pace-mapping (5-10 mm distance between pacing points) of the identified ventricular substrate. Using PASO Module, a pacing correlation map (PCM) was constructed based on the percentage match to the induced VT. Using the PCM and the measured stimulation to electrogram intervals, the potential VT critical isthmus was reconstructed. Radiofrequency ablation was carried out to completely transect the delineated isthmus. Post ablation, repeat HD mapping and ablation was performed, until the PASO % correlation dropped from >93% to <70%, indicating at least uni-directional (orthodromic to the perceived VT circuit) conduction block through the ablation line. Follow-up data, including ICD interrogations were collected via chart review. Outcomes were compared to 60 propensity-score matched patients with an ICD who were enrolled in the Ranolazine in High-Risk Patients with Implanted Cardioverter-Defibrillators (RAID) trial who did not undergo VT ablation and served as the control group. The primary endpoint was the first occurrence of any VT at 1-year of follow-up. Results Patients enrolled had a mean age of 69 ± 9 years and 13% were women. Propensity matched patients from the RAID trial had similar baseline clinical characteristics to patients who underwent VT ablation (Table). At 1 year follow up, there was a significantly lower cumulative probability of VT/VF recurrent events in the patients who underwent PCM guided ablation as compared with the control group (17% vs 69%, respectively; log-rank p<0.001 Figure). There were no serious procedure related complications with all patients remaining free of adverse events or death at 30 days. Conclusion Our findings suggest that ablation for unstable or unmappable VT is enhanced by ultra-high density pace-mapping to reconstruct the potential VT circuit and is associated with a significantly lower rate of recurrent VT as compared with patients managed with aggressive and escalating medical therapy.Cumulative probability of ICD therapyBaseline clinical characteristics

Impact of functional gene groups on outcomes after ablation of ventricular tachycardia in patients with inherited left ventricular cardiomyopathy: an international multicentre study

Abstract Background Advances in genetic testing has enabled identification of pathogenic variants of different functional gene groups associated with non-dilated left ventricular cardiomyopathy (NDLCM)/dilated cardiomyopathy (DCM) and ventricular tachycardia (VT). However, there is limited data on the impact of functional groups on VT ablation outcome. Aim We aimed to assess the impact of likely pathogenic/pathogenic variants (LP/Pv) of different functional gene groups on heart failure (HF) outcomes and VT recurrence in patients with NDLCM/DCM after VT ablation. Methods Patients with NDLCM/DCM who underwent genetic testing (next-generation sequencing) and were referred for VT ablation were enrolled at 6 participating centers. Patients were followed for VT recurrence, HF-related adverse outcomes (death, left ventricular assist device [LVAD], or heart transplantation due to HF), and all-cause mortality. Results A total of 239 patients (age 55±14yrs; male n=193; LVEF 40±12%; amiodarone at admission n=103; ICD n=180) were included. LP/Pv were identified in 128 patients (54%), predominantly found in genes encoding sarcomeric (n=36/128, [28%]; titin n=20, myosin binding protein C n=12), followed by nuclear membrane (n=27/128, [22%]; lamin A/C; n=26), desmosomal (n=23/128, [18%]; desmoplakin n=11, plakophilin n=9), cytoskeleton (n=12/128, [9%]; filamin C n=8), and sarcoplasmic reticulum proteins (n=12/128, [9%]; phospholamban n=10). Variants of unknown significance (n=32) were grouped with patients who tested negative. Acute complete ablation success, defined as non-VT inducibility of any sustained monomorphic VT, was achieved in 113 patients (47%), 63 (56%) with LP/Pv. During a median follow-up of 32 months, 108 patients (45%) had VT recurrence, 41 (17%) had HF-related adverse outcomes (death with/without LVAD in 34, LVAD in 2, heart transplantation in 5) and 47 (20%) died. Patients with LP/Pv were more likely to have VT recurrence, HF-related adverse outcomes and had a higher mortality compared to those without (VT, 68 [53%] vs. 40 [36%]; HF-related adverse outcomes, 30 [23%] vs. 11 [10%]; mortality, 30 [23%] vs. 17 [15%]; log-rank, P<0.01 for all). As compared to patients without LP/Pv, those with LP/Pv in genes encoding nuclear membrane or sarcomeric proteins had significantly worse (P<0.01 for both) and those with LP/Pv in genes encoding desmosomal proteins had similar HF and VT recurrence outcomes (Figure). Of interest, patients with LP/Pv in genes encoding cytoskeleton proteins had favorable HF-related adverse outcomes, but worse VT recurrence (P=0.02) compared to those without LP/Pv (Figure). Conclusion In patients with NDLCM/DCM and VT, the impact of LP/Pv on HF and VT-recurrence outcomes after ablation differs across functional groups. Integrating genetic testing in the comprehensive evaluation of patients with NDLCM/DCM undergoing VT ablation may facilitate personalized ablation strategies and early consideration of alternative HF treatments.

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

Inhalation exposure to flavored electronic nicotine delivery systems (vaping) negatively impacts cardiac electrophysiology

Abstract Background Electronic nicotine delivery systems (ENDS) heat "e-liquids" to generate "e-vapor", an inhalable aerosol. E-liquids contain nicotine and flavors in a solvent of 70% vegetable glycerin, 30% propylene glycol (70VG/30PG). Flavored ENDS are very popular among teens vapers, however, the possible cardiac electrophysiological harm of inhalation exposure to flavored ENDS are not fully understood. Purpose To test if inhalation exposure to e-liquids or their constituents compromises mitochondrial integrity, increases oxidative stress, and leads to cardiac electrophysiological toxicity. Methods Gas chromatography mass spectrometry (GC/MS), and flow cytometry, in-vivo programmed electrical stimulation (PES), and transmission electron microscopy (TEM) were used in atrial like HL-1 myocytes and in mice overexpressing the antioxidant mitochondrial catalase (MCAT) which underwent inhalation exposure to e-vapor. Results We compared the toxicity of e-vapor exposure to 30 differently flavored e-liquids (70VG/30PG, with 6 mg/ml nicotine) in HL-1 cells using annexinV flow cytometry. Most e-liquids were toxic. We then quantified the concentrations of major flavoring carbonyls (cinnamaldehyde, vanillin, ethyl-vanillin, maltol, and ethyl-maltol) in the 30 e-liquids using GC/MS. Toxicity of the e-liquids in HL-1 cells correlated with their flavoring carbonyls concentration. We assessed oxidative stress (OS) via CellROX flow cytometry in HL-1 cells exposed to vanilla flavored e-vapor. OS increased in exposed cells but this was blunted by N-acetylcycteine pretreatment. In-vivo inhalation exposure to e-vapor of vanilla flavored e-liquid with 6 mg/ml nicotine increased inducible ventricular tachycardia duration in WT but not in MCAT mice versus control. In TEM, mitochondrial perimeter was unaffected, but cristae thickness decreased in exposed WT, but not in exposed MCAT hearts versus controls. We then investigated whether adverse cardiac effects of vaping are due only to nicotine. Mice were exposed to the e-vapor of 70VG/30PG base alone or base plus vanillin WITHOUT nicotine. In telemetric ECG analysis of heart rate variability, exposure to base plus vanillin decreased parasympathetic indices more than exposure to base alone. In PES, the effective refractory periods of base alone and base plus vanillin groups tended to be shortened vs air controls. While exposure to base alone and to base plus vanillin significantly increased inducible ventricular tachycardia duration compared to air controls, the increase in the base plus vanillin group was more significant compared to that of base alone. Conclusions Inhalation exposure to flavored ENDS or to their NON-NICOTINE constituents negatively affects ventricular electrophysiology, possibly via adverse mitochondrial remodeling, and increased oxidative stress.

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.

BRUGADA SYNDROME: NEWEST DATA ON RISK STRATIFICATION

Abstract Background Brugada Syndrome (BrS) is a rare genetically based channelopathy responsible for malignant arrhythmias and sudden cardiac death (SCD) in young adults. Objectives The aims was to evaluate prognostic indicators useful for accurate arrhythmic risk stratification in BrS by studying genetic, clinical, anamnestic, instrumental parameters, and those derived from electrophysiological study (EPS) and intracavitary mapping. Materials and Methods 209 patients with Brugada type 1 were recruited between 01/01/2018 and 01/10/2023. Results In the first study, predictive factors related to high arrhythmic risk from the data obtained for the total population of 209 Brugada patients enrolled in our case series include a positive history of cardiogenic syncope (p value 0.000041), having had a resuscitated cardiac arrest (p value 0.00025), presenting positive EPS for inducibility of ventricular tachycardia (p value 0.00032), having a family history of sudden cardiac death (p value < 0.00001), and presenting positive cardiac mapping and MRI for pathological alterations (both with p value > 0.00001). From the data obtained for the subset of 80 Brugada patients with ICD in our case series, predictive factors related to high arrhythmic risk are different from the previously analyzed population: presenting spontaneous type 1 ECG (p value 0.0015), having had a resuscitated cardiac arrest (p value 0.014028), having a family history of sudden cardiac death (p value < 0.00001), and presenting positive mapping, genetics, and cardiac MRI for pathological alterations. Positive EPS and syncope in this subset do not appear to be risk factors, unlike the population of all 209 enrolled patients. Conclusions Multiparametric scores, including the mentioned markers, have been introduced in clinical practice for a better approach in selection. However, new markers are needed to improve risk stratification in BrS patients, especially those in the so–called "gray zone" with intermediate risk. In the future, it will be evaluated through experimental models and genotype–phenotype integration whether such electrical heterogeneity is also associated with specific genetic or structural abnormalities and may represent a new therapeutic target for etiological treatment in BrS patients. In conclusion, there is an urgent need to develop new methods for risk stratification in Brugada syndrome that are sufficiently sensitive, specific, reproducible, and easy to apply.

Antiarrhythmic and Anti-Inflammatory Effects of Sacubitril/Valsartan on Post-Myocardial Infarction Scar.

Sacubitril/valsartan (Sac/Val) is superior to angiotensin-converting enzyme inhibitors in reducing the risk of heart failure hospitalization and cardiovascular death, but its mechanistic data on myocardial scar after myocardial infarction (MI) are lacking. The objective of this work was to assess the effects of Sac/Val on inflammation, fibrosis, electrophysiological properties, and ventricular tachycardia inducibility in post-MI scar remodeling in swine. After MI, 22 pigs were randomized to receive β-blocker (BB; control, n=8) or BB+Sac/Val (Sac/Val, n=9). The systemic immune response was monitored. Cardiac magnetic resonance data were acquired at 2-day and 29-day post MI to assess ventricular remodeling. Programmed electrical stimulation and high-density mapping were performed at 30-day post MI to assess ventricular tachycardia inducibility. Myocardial samples were collected for histological analysis. Compared with BB, BB+Sac/Val reduced acute circulating leukocytes (P=0.009) and interleukin-12 levels (P=0.024) at 2-day post MI, decreased C-C chemokine receptor type 2 expression in monocytes (P=0.047) at 15-day post MI, and reduced scar mass (P=0.046) and border zone mass (P=0.043). It also lowered the number and mass of border zone corridors (P=0.009 and P=0.026, respectively), scar collagen I content (P=0.049), and collagen I/III ratio (P=0.040). Sac/Val reduced ventricular tachycardia inducibility (P=0.034) and the number of deceleration zones (P=0.016). After MI, compared with BB, BB+Sac/Val was associated with reduced acute systemic inflammatory markers, reduced total scar and border zone mass on late gadolinium-enhanced magnetic resonance imaging, and lower ventricular tachycardia inducibility.

Sinus rhythm activation signature indicates reentrant ventricular tachycardia inducibility and approximate isthmus location

BackgroundSinus rhythm activation time is useful to assess infarct border zone substrate. ObjectiveWe sought to further investigate sinus activation in ventricular tachycardia (VT). MethodsCanine postinfarction data were analyzed retrospectively. In each experiment, an infarct was created in the left ventricular wall by left anterior descending coronary artery ligation. At 3 to 5 days after ligation, 196–312 bipolar electrograms were recorded from the anterior left ventricular epicardium overlapping the infarct border zone. Sustained monomorphic VT was induced by premature electrical stimulation in 50 experiments and was noninducible in 43 experiments. Acquired sinus rhythm and VT electrograms were marked for electrical activation time, and activation maps of representative sinus rhythm and VT cycles were constructed. The sinus rhythm activation signature was defined as the cumulative number of multielectrode recording sites that had activated per time epoch, and its derivative was used to predict VT inducibility and to define the sinus rhythm slow/late activation sequence. ResultsPlotting mean activation signature derivative, a best cutoff value was useful to separate experiments with reentrant VT inducibility (sensitivity, 42/50) vs noninducibility (specificity, 39/43), with an accuracy of 81 of 93. For the 50 experiments with inducible VT, recording sites overlying a segment of isochrone encompassing the sinus rhythm slow/late activation sequence spanned the VT isthmus location in 32 cases (64%), partially spanned it in 15 cases (30%), but did not span it in 3 cases (6%). ConclusionThe sinus rhythm activation signature derivative is assistive to differentiate substrate supporting reentrant VT inducibility vs noninducibility and to identify slow/late activation for targeting isthmus location.

Ventricular arrhythmias in patients with bicuspid aortic valves.

Bicuspid aortic valves (BAV) are the most common congenital heart defects and the extent of ventricular arrhythmias (VA) in patients with BAV is unclear. The objective of this study is to describe VAs and late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) in patients with BAV. A total of 19 patients with BAV (18 males, age: 58 ± 13 years) were referred for VA ablation procedures. Ten patients had BAVs at the time of ablation, nine patients had prior aortic valve replacement for a BAV. All but one patient had LGE-CMR and all patients underwent programmed ventricular stimulation at the time of the ablation. Frequent PVCs were the targeted VAs in 17/19 patients and VT in 2/19 patients. Monomorphic ventricular tachycardia (VT) was inducible in 6 patients. A total of 15 VTs were inducible (2.5 ± 1.0 VTs per patient with a mean cycle length of 322 ± 83 msec). LGE was present in 13 patients. Patients with inducible VT had larger borderzone and core scar compared to non-inducible patients (7.8 ± 2.1 cm3 vs. 2.5 ± 3.1 cm3 and 5.1 ± 2.6 cm3 vs. 1.9 ± 3.0 cm3, p-value < .05 for both). PVCs and VTs were mapped to the periaortic valve area in 12 patients and 4 patients, respectively. The PVC burden was reduced from 27 ± 13 to 3 ± 6 (p < .001) and the ejection fraction improved from 49 ± 13% to 55 ± 9% (p = .005). VAs in patients with BAV often originate from the perivalvular area and patients often have LGE and inducible VT. LGE may be due to ventricular remodeling secondary to the presence of BAV and harbors the arrhythmogenic substrate for VT.

Intramural needle ablation or repeated standard ablation in patients referred for repeat ablation of scar-related ventricular tachycardia.

When ventricular tachycardia (VT) recurs after standard RF ablation (sRFA) some patients benefit from repeat sRFA, whereas others warrant advanced methods such as intramural needle ablation (INA). Our objectives are to assess the utility of repeat sRFA and to clarify the benefit of INA when repeat sRFA fails in patients with VT due to structural heart disease. In consecutive patients who were prospectively enrolled in a study for INA for recurrent sustained monomorphic VT despite sRFA, repeat sRFA was considered first. INA was performed during the same procedure if repeat sRFA failed or no targets for sRFA were identified. Of 85 patients enrolled, acute success with repeat sRFA was achieved in 30 patients (35%), and during the 6-month follow-up, 87% (20/23) were free of VT hospitalization, 78% were free of any VT, and 7 were lost to follow-up. INA was performed in 55 patients (65%) after sRFA failed, or no endocardial targets were found abolished or modified inducible VT in 35/55 patients (64%). During follow-up, 72% (39/54) were free of VT hospitalization, 41% were free of any VT, and 1 was lost to follow-up. Overall, 59 out of 77 (77%) patients were free of hospitalization and 52% were free of any VT. Septal-origin VTs were more likely to need INA, whereas RV and papillary muscle VTs were less likely to require INA. Repeat sRFA was beneficial in 23% (18/77) of patients with recurrent sustained VT who were referred for INA. The availability of INA increased favorable outcomes to 52%.

Prognostic value of noninvasive programmed stimulation in primary prevention implantable cardioverter‐defibrillator recipients

AbstractBackgroundImplantable cardioverter‐defibrillator (ICD) offers an opportunity to study inducibility of ventricular tachycardia (VT) or ventricular fibrillation (VF) by performing noninvasive programmed ventricular stimulation (NIPS). Whether NIPS can predict future arrhythmic events or mortality in patients with primary prevention ICD, has not yet been examined.MethodsFrom the NIPS‐ICD study (ClinicalTrials ID: NCT02373306) 41 consecutive patients (34 males, age 64 ± 11 years, 76% ischemic cardiomyopathy [ICM]) had ICD for primary prevention indication. Patients underwent NIPS using a standardized protocol of up to three premature extrastimuli at 600, 500 and 400 ms drive cycle lengths. NIPS was classified as positive if sustained VT or VF was induced. The study endpoint was occurrence of sustained VT/VF during the follow‐up.ResultsAt baseline NIPS, VT/VF was induced in 8 (20%) ICM patients. During the 5‐year follow‐up, the VT/VF occurred in 7 (17%) patients, all with ICM. The difference between NIPS‐inducible versus NIPS‐noninducible patients regarding VT/VF occurrence did not meet statistical significance (38% vs. 12%, log rank test p = .11). After a 5‐year follow‐up, the mortality rate was significantly higher in patients who had VT/VF induced at NIPS versus no VT/VF at NIPS (38% vs. 12%, p = .043). The occurrence of a composite endpoint consisting of VT/VF recurrence or death in patients with ICM was also most frequent in the NIPS‐inducible group (75% vs. 35%, p = .037).ConclusionsInducibility of VT/VF during NIPS in ICM patients with primary prevention ICD is associated with higher mortality and higher incidence of composite endpoint consisting of death or VT/VF during a long‐term observation.

Automated cardiac arrest detection using a photoplethysmography wristband: algorithm development and validation in patients with induced circulatory arrest in the DETECT-1 study

Unwitnessed out-of-hospital cardiac arrest is associated with low survival chances because of the delayed activation of the emergency medical system in most cases. Automated cardiac arrest detection and alarming using biosensor technology would offer a potential solution to provide early help. We developed and validated an algorithm for automated circulatory arrest detection using wrist-derived photoplethysmography from patients with induced circulatory arrests. In this prospective multicentre study in three university medical centres in the Netherlands, adult patients (aged 18 years or older) in whom short-lasting circulatory arrest was induced as part of routine practice (transcatheter aortic valve implantation, defibrillation testing, or ventricular tachycardia induction) were eligible for inclusion. Exclusion criteria were a known bilateral significant subclavian artery stenosis or medical issues interfering with the wearing of the wristband. After providing informed consent, patients were equipped with a photoplethysmography wristband during the procedure. Invasive arterial blood pressure and electrocardiography were continuously monitored as the reference standard. Development of the photoplethysmography algorithm was based on three consecutive training cohorts. For each cohort, patients were consecutively enrolled. When a total of 50 patients with at least one event of circulatory arrest were enrolled, that cohort was closed. Validation was performed on the fourth set of included patients. The primary outcome was sensitivity for the detection of circulatory arrest. Of 306 patients enrolled between March 14, 2022, and April 21, 2023, 291 patients were included in the data analysis. In the development phase (n=205), the first training set yielded a sensitivity for circulatory arrest detection of 100% (95% CI 94-100) and four false positive alarms; the second training set yielded a sensitivity of 100% (94-100), with six false positive alarms; and the third training set yielded a sensitivity of 100% (94-100), with two false positive alarms. In the validation phase (n=86), the sensitivity for circulatory arrest detection was 98% (92-100) and 11 false positive circulatory arrest alarms. The positive predictive value was 90% (95% CI 82-94). The automated detection of induced circulatory arrests using wrist-derived photoplethysmography is feasible with good sensitivity and low false positives. These promising findings warrant further development of this wearable technology to enable automated cardiac arrest detection and alarming in a home setting. Dutch Heart Foundation (Hartstichting).

Automated isochronal late activation mapping for substrate characterization in patients with repaired tetralogy of Fallot.

Slow conduction (SC) anatomical isthmuses (AIs) are the dominant substrate for monomorphic ventricular tachycardia (VT) in patients with repaired tetralogy of Fallot (rTF). This study aimed to evaluate the utility of automated propagational analysis for the identification of SC-AI in patients with rTF. Consecutive rTF patients undergoing VT substrate characterization were included. Automated isochronal late activation maps (ILAM) were obtained with multielectrode HD Grid Catheter. Identified deceleration zones (DZs) were compared with both SC-AI defined by conduction velocity (CV) (<0.5 m/s) and isthmuses of induced VT for mechanistic correlation. Fourteen patients were included (age 48; p25-75 35-52 years; 57% male), 2 with spontaneous VT and 12 for risk stratification. Nine VTs were inducible in seven patients. Procedure time was 140 (p25-75 133-180) min and mapping time 29.5 (p25-75 20-37.7) min, using a median of 2167 points. All the patients had at least one AI by substrate mapping, identifying a total of 27 (11 SC-AIs). Isochronal late activation maps detected 10 DZs mostly in the AI between ventricular septal defect and pulmonary valve (80%). Five patients had no DZs. A significant negative correlation between number of isochrones/cm and CV was observed (rho -0.87; P < 0.001). Deceleration zones correctly identified SC-AI (90% sensitivity; 100% specificity; 0.94 accuracy) and was related to VT inducibility (P = 0.006). Deceleration zones co-localized to the critical isthmus of induced VTs in 88% of cases. No complications were observed. Deceleration zones displayed by ILAM during sinus rhythm accurately identify SC-AIs in rTF patients allowing a safe and short-time VT substrate characterization procedure.