ICD Shocks Research Articles

PO-04-159 PREVALENCE AND CHARACTERISTICS OF PATIENTS WITH LONG QT SYNDROME (LQTS) WHO APPEAR NON-RESPONSIVE TO CONVENTIONAL LQTS THERAPIES

Long QT syndrome (LQTS) is a potentially lethal cardiac channelopathy with a 1% to 5% annual risk of LQTS-triggered syncope/seizures or sudden cardiac arrest/death (SCA/SCD). Despite maximal LQTS-directed therapies, a subset of patients experience breakthrough cardiac events (BCEs). To describe the phenotype of “non-responders” defined as LQTS patients with recurrent BCEs despite maximal LQTS-directed therapy. Among the 1731 LQTS patients evaluated and treated at Mayo Clinic, a retrospective analysis was performed to identify those who experienced ≥1 BCE while on maximum treatment (combination of ≥2 device/denervation and/or pharmacologic therapies at maximally tolerated doses). Basic demographics, clinical characteristics, and frequency/type of BCEs defined as syncope/seizures, appropriate ICD shocks, SCA, or SCD were extracted from the electronic medical record. Overall, 32/1731 LQTS patients (2%) experienced ≥1 BCE with 13 (41%) occurring in the setting of medication nonadherence. Of the remaining 19 patients (1% of all LQTS patients; 37% female, mean age at last event of 11±8 years and mean QTc of 537±92ms), 7 (37%) had compound heterozygous (n=6) or homozygous (n=1) disease involving either KCNQ1 or KCNH2, including one Jervell and Lange-Nielsen syndrome patient, and 2 (11%) had high-risk minor LQTS genotypes (CALM2-mediated LQTS and CACNA1C-mediated Timothy syndrome). Notably, 5 (26%) had a complex cardiac sodium channelopathy with predominant features of LQT3 and multifocal ectopic Purkinje-related premature contractions. The remaining patients had treatment-refractory LQT2 (n=3; 16%) or LQT3 (n=2; 11%). At last follow-up, 2 patients (11%) died and 4 (2%) underwent cardiac transplant. For the remaining 13 patients, treatment was escalated after their last BCE. Twelve patients (92%) received an ICD and either atrial pacing (AP) + beta-blocker (BB) + mexiletine (MEX) [n=1, 8%], AP + left cardiac sympathetic denervation (LCSD) + ≥2 antiarrhythmic drugs (AADs) [n=4, 31%], bilateral denervation + BB [n=2, 15%], or LCSD + ≥1 AAD [n=5, 38%]. One patient (8%) was on LCSD + BB + MEX. Despite safe and effective treatment options, 1% of LQTS patients experience recurrent BCEs on maximal LQTS-directed therapy. Adherence to the outlined treatment program needs to be reinforced. In addition, compound heterozygous/homozygous KCNQ1-mediated disease and complex SCN5A-mediated channelopathies represent high-risk LQTS subsets in need of alternative management strategies.

PO-05-135 SIGNAL-AVERAGED ECG IN THE NORDIC ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY REGISTRY: ASSOCIATION WITH PREVALENT LIFE-THREATENING ARRHYTHMIAS AND ASCERTAINMENT OF CLINICAL DIAGNOSIS.

In arrhythmogenic right ventricular cardiomyopathy (ARVC), minor depolarization criteria by TFC2010 include ventricular late potentials (LP) assessed using signal-averaged ECG (SAECG) and terminal activation duration (TAD). TAD is measured from a standard V1 lead, which favors its use in clinical practice, however its ability to fully replace LP in ARVC workup is not clear. 1. To assess the association between TAD and LP and the prevalence of life-threatening ventricular arrhythmias in patients with ARVC. 2. To assess diagnostic impact of SAECG by characterizing the subgroup of patients, who would not have received definite ARVC diagnosis if LP were not considered. Patients with definite ARVC or genotype-positive family members who underwent SAECG were included (n=358, 47% women, age 41±16 years, 43% probands, 67% definite ARVC). LP and TAD were defined according to TFC2010 criteria. TFC score was calculated by assigning 2 points for major and 1 for minor criterium. Ventricular tachycardia (VT) was defined as sustained VT, aborted cardiac arrest or appropriate ICD shock. Logistic regression adjusted for clinical covariates was used to test association of TAD and LP with prevalent VT. In a subgroup of patients with TFC score 4, i.e. minimally required for diagnosis, patients who would be reclassified into borderline category if LP not considered (LP-dependent, n=38) were compared with those who had TFC score 4 regardless of LP (LP-independent, n=30) in terms of proband status, prevalence of imaging criteria and VT. LP were found in 209 patients (58%); TAD in 65 (18%); 90 patients had prevalent VT (25%). LP was associated with prevalent VT (OR=2.5 95%CI 1.2-5.3; Sensitivity 84%, Specificity 50%) while TAD was not (OR=1.6 95%CI 0.7-3.6; Sensitivity 32%, Specificity 87%). In the LP-dependent group, 9 of 14 (64 %) probands had prevalent VT, 7 (50%) survived cardiac arrest and 4 (29%) were genotype-positive. Clinical characteristics did not demonstrate significant differences between LP-dependent and LP-independent subgroups. LP is independently associated with VT and is more sensitive than TAD in identification of patients with prevalent VT. LP were critical for ascertainment of ARVC diagnosis required for initiation of family screening in 9% probands. Although the diagnostic impact of LP varies depending on SAECG availability, our data support its use as a sensitive non-invasive diagnostic tool.

PO-04-202 RESUSCITATED OUT OF HOSPITAL CARDIAC ARREST AS THE INITIAL PRESENTATION OF HYPERTROPHIC CARDIOMYOPATHY

Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy, and it is associated with ventricular arrhythmias and sudden death. Out-of-hospital cardiac arrest (OHCA) may be the first presentation of HCM in some patients. To determine the frequency of resuscitated OHCA as the initial presentation of HCM, as well as the characteristics, initial management, and outcomes of these patients. Patients with HCM were identified with a comprehensive phenotyping approach, including natural language processing of electronic medical records, cardiac imaging reports, and diagnosis codes. HCM diagnoses were validated by trained reviewers. Among these, we focused on patients who had resuscitated OHCA as the initial presentation leading to the HCM diagnosis. Baseline characteristics, HCM treatments and outcomes were obtained from the electronic medical record. Of 6,276 patients diagnosed with HCM at our institution between 2001-2019, we identified 29 (0.5%) patients with resuscitated OHCA as their initial HCM presentation (17% female; mean age at the time of OHCA 34 ± 17 years). Ventricular tachyarrhythmia was the confirmed cause of OHCA in 24 patients. No patients had a primary acute coronary event as the etiology of OHCA. The median of the thickest wall segment was 30.5 mm and 8 (28%) patients had obstructive HCM. An apical pouch was present in 5 (17%) patients. All patients underwent ICD implantation following OHCA and survived hospital discharge. The mean follow-up post-OHCA was 9 ± 6.6 years. During follow-up, 13 (45%) patients underwent septal reduction therapy. 8 (28%) patients had at least one appropriate ICD shock or antitachycardia pacing event for VT/VF. Two (7%) patients died during follow-up, one from a cardiac non-arrhythmic cause and one from an unknown cause. Resuscitated OHCA is an infrequent initial presentation of HCM. These patients remain at risk for recurrent VT/VF, but overall long-term survival is favorable with secondary prevention ICDs and other HCM-directed therapies.

PO-05-036 PERCUTANEOUS STELLATE GANGLIA ABLATION IN THE MANAGEMENT OF VTSTORM

VT storm is a clinical emergency associated with high mortality. Neural modulation of the cardiac sympathetic chain, usually in the form of surgical sympathectomy, has shown to be effective in achieving reduction in appropriate ICD shocks and VT episodes. We hypothesised Percutaneous Stellate Ganglion Ablation (SGA) is a safe and effective alternative modality of neuromodulation in patients with VT storm. Patients with ES refractory to standard management, including sedation and mechanical ventilation, antiarrhythmic agents and beta-blockers, underwent bilateral percutaneous SGA. The ablation was performed at 2 levels - C7 and T1, bilaterally, under fluoroscopic guidance using a customized protocol. (Figure) At each site, 3 lesions were delivered sequentially at 50, 55 and 60 deg. C for 90 seconds using a COSMAN RF generator and RF needle electrode of 5cm length and 4mm active tip with ipsilateral Horner’s syndrome being the clinical end-point for successful ablation. Patients were followed up till discharge and as outpatients with periodic device interrogation There were 6 patients with refractory VT storm (4 male & 2 female) with a mean age of 56.5±5.2 years. The VT was monomorphic in 4 and polymorphic in the other 2 patients. The substrate was Ischaemic cardiomyopathy in 2, Non-ischaemic cardiomyopathy in 3 and Hypertrophic cardiomyopathy in 1 patient. The meean LVEF was 35 ± 20%. There were no periprocedural complications. Post-procedure, 2 out of the 6 patients had one episode of Non-sustained VT each in-hospital. All patients were discharged on Amiodarone and Metoprolol. The mean follow-up duration was 15± 3 months. At last follow-up all of them are alive and none of then received any shocks.. One patient had a VT at 42 days after procedUre which was terminated by device using ATP. SGA by RFA is a safe, effective, inexpensive, well-tolerated and minimally invasive procedure for neuromodulation and should be considered in drug refractory ES.

PO-04-191 RISK FACTORS AND OUTCOMES OF EARLY VENTRICULAR ARRHYTHMIAS AFTER LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION

Ventricular arrhythmias (VAs) may occur during the early post-operative period after the implantation of left ventricular assist device (LVAD). The factors associated with its development and the long-term clinical outcome are unclear. This study aimed to evaluate the risk factors and outcomes of early ventricular arrhythmias <30 days after LVAD implantation. We performed a retrospective cohort study on all patients who underwent LVAD implantation at the Mayo Clinic (Rochester, Phoenix, and Jacksonville) from January 1, 2001, to December 31, 2020. Early VAs were defined as sustained (>30 seconds) ventricular tachycardia or ventricular fibrillation occurring less than 30 days after the LVAD implantation. Detailed review of the electronic health records within the Mayo Clinic and outside medical records were performed. A total of 886 patients were included in the study, with a median age of 60 years (interquartile range [IQR]: 50-67), and 78.9% were male. A total of 195 (22.1%) patients had early VAs after LVAD implant. Pre-implant characteristics associated with early VAs were history of VAs (32.8% vs 23.9% p=0.012), history of ventricular tachycardia ablation (5.6% vs 2.0%, p=0.007), history of ICD shocks (32.3% vs 20.1%, p<0.001) and the use of mexiletine (16.4% vs 5.9%, p<0.001) and sotalol (8.2% vs 3.6% p=0.007) before LVAD. There was no difference in the subsequent risk of late VAs in patients with or without early VAs (27.7% vs. 25.8%, p=0.29). The 1-year post LVAD mortality rate was higher in patients with early VAs compared to patients without early VAs (32% vs 18%, P<0.01). Early VAs occur in 22.1% of patients undergoing LVAD implant and is associated with increased 1-year post LVAD mortality. Significant pre-implant risk factors include a history of VAs, ICD shocks, and anti-arrhythmic drug use before the procedure.

CE-452777-1 INCIDENCE, PREDICTORS AND CLINICAL SIGNIFICANCE OF LATE VENTRICULAR ARRHYTHMIAS AFTER LVAD IMPLANTATION

Long-term survival after durable left ventricular assist device (LVAD) is improving. Ventricular arrhythmias are a driver of patient morbidity following implantation. Predictors of late ventricular arrhythmias (LVA) and their prognostic significance remain uncertain. We sought to determine the incidence of LVA, risk factors associated with their development and their clinical impact on patients in patients after LVAD implantation in long-term follow-up. A single-center retrospective analysis was performed including patients who underwent LVAD implantation from 2007-2022. We compared clinical characteristics and outcomes between patients who developed LVA to those patients without LVA. LVAs were defined as an episode of sustained ventricular tachycardia or ventricular fibrillation identified on ECG, telemetry and/or CIED occurring >30 days after LVAD implantation. Transplant-free survival was defined as time from index LVAD implantation to transplantation, LVAD explantation, death or most-recent follow-up. Of the 788 patients who underwent LVAD implantation during the study period, 141 patients (21.9%) had LVA >30 days after LVAD implantation. There was no significant difference between ages of patients with LVA and those without ventricular arrhythmia following LVAD implantation (LVA vs no LVA: 63.2 vs 62.3 years; p = 0.556). The majority of patients were male (78.7% vs 71.8%; p = 0.102) and self-identified as black (70.9% vs 71.8%; p = 0.875). Patients with LVAs more often had a history of preoperative presence of CRT (22.9% vs 12.5%; p = 0.002), history of ventricular tachycardia (49.3% vs 30.0%; p = <0.001), history of atrial flutter ablation (10.7% vs 3.7%; 0.001), appropriate ICD therapy prior to implantation (15.7% vs 5.5%; p = <0.001), taking amiodarone (31.8% vs 21.9%; p = 0.023), larger LVEDD (7.0 cm ± 1.0 vs 6.8 cm ± 1.0; p = 0.013) and QTc prolongation (504.8 ms ± 56.5 vs 518.2 ms ± 50.3; p = 0.017). The strongest independent predictors of LVA were a history of atrial flutter ablation (OR 3.52; CI 1.43-8.62; p = 0.006) and appropriate ICD shock in 7 days prior to implantation (OR 3.22; CI 1.49-6.99; p = 0.003). There was no difference between transplant-free survival time in patients with and without LVAs (p = 0.062, Figure 1). Despite being a common event after LVAD therapy, the development of LVA does not adversely impact transplant-free survival time. Future studies are warranted to determine the impact of LVA on quality-of-life in LVAD patients.

MP-453083-11 SAFETY AND OUTCOMES OF VENTRICULAR TACHYCARDIA ABLATION ACROSS AGE GROUPS

A pharmacotherapy approach to the treatment of ventricular tachycardia (VT) is frequently complicated by poor tolerance, persistent ICD shocks and impartial rhythm control. This can be burdensome in an elderly population who frequently have significant comorbidities complicating medical care. Catheter ablation for ventricular tachycardia has been increasingly employed to treat VT, however a paucity of data on the safety and outcomes of VT ablation in octogenarians exists. To examine the safety and outcomes of ventricular tachycardia ablation therapy in octogenarians. The data used was obtained from the National Inpatient Sample (NIS) database from 2016 to 2019. We identified patients ≥ 21 years old with VT as primary diagnoses and underwent ablation during index hospitalization. Patients were divided into 4 age subgroups 20-39, 40-59, 60-79 and ≥ 80 years old. Primary outcome was all-cause mortality and secondary outcomes were transfer to rehab, hospital length-of-stay and in-hospital complications. Univariate and multivariate logistic regression analyses were used to study the association between catheter ablation and primary and secondary outcomes. A total of 23,900 patients undergoing VT ablation were identified. Most patients were between ages of 50-69 years of age (60.3%), followed by 40-59 (25%), ≥ 80 (9.5%), and 20-39 (5.6%). No significant differences in complications including procedure-related pericardial effusion, pericarditis, tamponade, stroke, hemorrhage, or respiratory failure were seen between all age groups. Similarly, no significant differences in hospital length of stay were appreciated across all ages. However, mortality rates were significantly higher in octogenarians (4.2%), compared to those between 60-79 years old (3.2%), 40-59 years (1.5%) and 20-39 years (2.3%) (p-value 0.023). Rehab transfer was also significantly higher in the elderly (p-value <0.001). In this large, real-world database study, we found no significant differences in procedure related complications or hospital length of stay across all age groups undergoing VT ablation. However, in-hospital mortality rates and transfer to rehab were significantly higher in octogenarians compared to younger subgroups. Despite procedural safety, a decision to pursue VT ablation in octogenarians must be carefully weighed against modest increased risks of mortality in this delicate population.

PO-04-045 HOW TO VISUALIZE BIPOLAR ABLATION CATHETERS ON 3D MAPPING FOR BIPOLAR RADIOFREQUENCY CATHETER ABLATION AND MINIMIZE FLUOROSCOPY

Bipolar radiofrequency catheter ablation (RFCA) strategy using two ablation catheters may require prolonged fluoroscopy time because of challenges with catheter positioning. Intracardiac echocardiographic images may only offer limited views to help maneuver both ablation catheters. To simultaneously visualize both ablation catheters on the 3D mapping system for localizing the ablation target and minimizing fluoroscopy. A bipolar RFCA system was set up with connections to the grounding pad and two distal pins connected to the distal electrodes of the THERMOCOOL SMARTTOUCH® SF ablation catheter (Biosense Webster) with 1-6-2mm spacing (Figure A). Case 1: A 51-year-old male with familial HCM presented with VT storm for which he was externally cardioverted. The patient underwent VT ablation during which the VT was localized to LV summit. Due to difficulty achieving transmural lesions with unipolar ablation, bipolar RFCA with two ablation catheters on posteroseptal RVOT and below the RCC was performed with successful elimination of the clinical VT. The distal 3rd and 4th electrodes on the second ablation catheter was connected to our bipolar circuit, which was visualized on CARTO® 3D mapping (Biosense Webster) (Figure B). Case 2: A 62-year-old male with a CRT-D for cardiac sarcoidosis and non-ischemic cardiomyopathy, and a recent endocardial VT ablation in the setting of VT storm presented with multiple ICD shocks. Patient underwent repeat ablation with further endocardial substrate modification and epicardial ablation. With the second ablation catheter on the epicardium, the distal 3rd and 4th electrodes were visualized, and the dome of the catheter tip was created on CARTO® (Figure C). The patient underwent an extensive endocardial and epicardial ablation but remained inducible with slower VT for which he underwent further heart transplant evaluation. Utilizing a novel bipolar RFCA set-up that allows visualization of both ablation catheters on the 3D mapping system may offer better target localization and less fluoroscopy exposure.

PO-03-145 BETA BLOCKERS IN PATIENTS WITH LONG QT SYNDROME: MOVING AWAY FROM ONE-SIZE-FITS-ALL?

Experts in the field recommend using nadolol at 1mg/kg/day and propranolol at 2-3mg/kg/day for patients with long QT syndrome (LQTS), but there are no available studies defining the most effective dose. In our experience, most but not all patients tolerate beta blocker at full dose. To describe our institutional experience with utilizing exercise stress testing (EST) in the subset of LQTS patients who did not tolerate standard beta-blocker dosing. We queried our Inherited Arrhythmia Registry and identified patients with LQTS who were on "submaximal" nadolol/propranolol doses (defined as < 1mg/kg/day for nadolol and < 2mg/kg/day for propranolol) and who had at least one follow up appointment. For those patients, we have devised a practical approach for demonstrating sufficient beta blockade effect by assessing for heart rate (HR) blunting at maximal exercise, which was defined as at least 15-20% decrease from maximal HR. Of 166 patients with LQTS, 51 (53% females, 53% probands) were on “submaximal” beta blocker therapy at time of last follow up and formed our study cohort. Median age at diagnosis and QTc were 15.8 yrs (range: 0.1-50.9 yrs) and 484 ms (400-610 ms) respectively. In terms of LQTS type: 24 had LQT1, 22 had LQT2, 2 had LQT5, 1 had LQT1 + LQT2, 1 had LQT3, and 1 patient had a VUS in CALM3 gene. Cardiac events included: cardiac arrest in 4 (8%) prompting ICD implantation, bradycardia-induced Torsades de Pointes in 2 (4%) prompting pacemaker implantation, recurrent cardiac syncope prompting sympathectomy in 2 (4%) and cardiac syncope in 10 (20%). The distribution of beta blocker dose is shown in Figure 1A and % predicted peak HR on EST as a function of beta blocker dose is shown in Figure 1B. EST data was available in 37 (73%) patients and demonstrated that HR blunting can be achieved with “submaximal” doses. Over a median follow up of 6.3 years and while on intentional “submaximal” beta blocker therapy, 1 (2%) patient had recurrent appropriate ICD shocks prompting referral for sympathectomy, and no patient (0/34, 0%) with adequate HR blunting had a cardiac event. In our institutional LQTS experience, adequate heart rate blunting may be achieved with "submaximal" beta blocker dose. EST may be a useful modality to devise an individualized treatment plan and titrate beta blocker dose to effect, especially in those that cannot tolerate the recommended guideline directed dose.

Superior vena cava isolation with pulsed field ablation in the presence of defibrillator leads.

Two patients with a history of dilated cardiomyopathy, dual chamber defibrillator implantation, and worsening heart failure because of persistent atrial fibrillation (AF) underwent catheter ablation of AF. Pulsed field ablation (PFA) was selected for the index procedure in these decompensated heart failure patients with enlarged atria.1 The 12-Fr over-the-wire pentaspline PFA catheter (Farawave) was advanced through a 13-Fr steerable sheath (Faradrive) to the ostium of each PV, and a total of eight PFA lesions were applied per vein. Phrenic nerve function was evaluated by direct phrenic capture and by observing diaphragmatic motion during inspiration. For posterior wall ablation, the catheter was placed into a flower configuration and positioned along the posterior left atrium to deliver overlapping sets of pulses at each location. As per institution protocol, superior vena cava (SVC), as a potential nonpulmonary trigger for AF, is isolated when active despite a risk of sinus node injury.2 Basket configuration (Figure 1) and two sets of two lesions at the trunk of the vessel (with rotation between each pair) were used for SVC isolation in the presence of atrial and defibrillator leads, without any impact on device and leads measurements or sinus node function (Figure 2). We observed incidence of phrenic capture during PFA, and no evidence of phrenic injury was detected after the procedure. Both patients were in AF and cardioverted into sinus rhythm post-SVC isolation. They remained at sinus rhythm at regular 3-month follow-up while device interrogation revealed intact sinus node function. Only 4.2% of operators in the MANIFEST-PF multinational survey (including 1758 consecutive unselected AF patients) performed SVC isolation by mean of PFA occasionally.3 This is the first report of off-label pulsed field ablation-mediated SVC isolation without device or lead malfunction. Human studies evaluating cardiac implantable electrical devices during ablation procedure remain limited. A recent study by a high-volume center indicated that PFA is a safe and feasible method in patients with devices in the terms of alterations in pacing, sensing, or impedance parameters, inappropriate anti-tachycardia pacing, and ICD shock and leads dislodgment.4 Indeed, our pilot procedures with PFA applications in the SVC of AF patients with implanted devices confirmed the previous results without apparent additional risk because of energy application adjacent to the electrodes. None declared. None. The authors declare no conflict of interests for this article. Approval of the research protocol: N/A. Informed Consent: Ν/Α. Registry and the Registration No. of the study/trial: N/A. Animal Studies: N/A. Data are available in the article.

Abstract P556: Temporal and Global Trends of the Incidence of Sudden Cardiac Death in Hypertrophic Cardiomyopathy: A Meta-Analysis

Introduction: Since hypertrophic cardiomyopathy(HCM) initial description, sudden cardiac death (SCD) has been the most feared complication of HCM. Hypothesis: Temporal, geographical, and age-related trends of SCD rates in HCM have drastically decreased over time. Methods: Databases were systematically searched to Nov 2021 for studies reporting on SCD event rates in HCM. Patients with SCD equivalents (appropriate ICD shocks and non-fatal SCD) were excluded. Random-e!ects model was utilized to pool study estimates calculating the overall incidence rates(IR) for each time-era, geographical region, and age-group. We analyzed 2 eras (before vs. after 2000, following implementation of ICD in HCM). Following 2000, 5-year intervals were used to reflect the temporal change in SCD. Results: 98 studies(N=70,510patients and 431,407patient-years) met inclusion criteria. Overall rate of HCM SCD was 0.43%/year (95% CI: 0.37-0.50%; I2=75%; SCD events:1,938; person-years of follow-up: 408,715), with young patients(&lt;18 years) demonstrating a&gt;2-fold-risk for SCD vs. adults(18- 60years) (IR:1.09%; 95% CI: 0.69-1.73% vs. IR: 0.43%; 95% CI: 0.37-0.50%)(P-value for subgroup di!erences:&lt;0.01). Contemporary SCD rates from 2015-present were 0.32%/year; significantly lower compared to 2000 or earlier (IR: 0.32%; 95% CI:0.20-0.52%, vs. IR: 0.73%; 95% CI:0.53-1.02%,respectively). Reported HCM-SCD rates were lowest in North America (IR: 0.28%;95% CI:0.18-0.43%) and highest in Asia(IR: 0.67%; 95% CI:0.54-0.84%). Conclusions: Contemporary HCM-related SCD are low (0.32%/year) representing a 2-fold decrease compared to prior treatment eras, with young HCM patients at the highest risk. SCD risk stratification maturation and primary prevention ICD application are likely responsible for the notable decline in SCD trends. Moreover, worldwide geographical disparities in SCD was evident, underscoring the need to increase access to SCD prevention for all HCM patients.

958 IMPACT OF CARDIAC SYMPATHETIC DENERVATION ON ELECTRICAL STORMS IN PATIENTS WITH CARDIOMIOPATHIES

Abstract Background Cardiac Sympathetic Denervation (CSD) has been recently proposed for the treatment of refractory ventricular arrhythmias (VAs) in patients with cardiomyopathy (CMP). A multicentric American and Indian case series suggested a greater efficacy of bilateral denervation (BCSD), compared to the left-side only procedure (LCSD), albeit with the potential prize of an increased need for atrial pacing due to the right-side innervation of the sinus node. The impact of CSD on the risk of electrical storms (ES) in CMP has never been evaluated. Aim To describe our multicenter Italian experience with CSD in CMP patients with drug and/or catheter ablation refractory VAs, with a specific focus on ES incidence. Methods Thirty patients with CMP and refractory VAs underwent either LCSD or BCSD between April 2016 and June 2022. Among them, one patient received first LCSD and then right-side denervation due to ES recurrence after LCSD: to properly assess the risk of ES after LCSD and BCSD he was included in both groups with the corresponding follow-up, leading to 5 cases of LCSD and 26 cases of BCSD. All patients had a Video–Assisted Thoracoscopic Surgery (VATS), in 8 cases associated with the robotic technique. The main reason (3/5 cases, 60%) to perform LCSD instead of BCSD since the beginning was sinus bradycardia in single ICD lead recipients. Results 87% of pts were male, the mean age was 56 ± 16 yrs and the mean LVEF 31± 12%; most (n=26, 85%) suffered non-ischemic cardiomyopathy and 37% were in NYHA functional class ≥3. Main indications for CSD were represented by refractory polymorphic/fast VAs (cycle length &amp;lt;250 msec) in 60% of pts and by refractory monomorphic VAs episodes in the rest. Except for 5 patients (17%) with previous thyrotoxicosis, the majority were either on amiodarone (n=19, 63%) or on sotalol (n=3, 10%) before CSD and 53% had previously undergone ≥1 catheter ablation for VAs. The median follow-up (FU) after denervation was 15 months (IQR 5-42 months). No major complication directly related to the procedure occurred. Overall, 11 patients (37%) either died during FU (n=8, 27%), mostly due to end-stage heart failure, or underwent heart transplant (n=3, 10%). After denervation, the percentage of patients with ES decreased from 77% to 40% (p&amp;lt;0.01), while patients with appropriate shocks decreased from 100% to 60%. The antiarrhythmic benefit was even more pronounced among the 26 patients who received BCSD: ES incidence decreased from 85% to 39% (p&amp;lt;0.01), appropriate shock incidence from 100% to 54% (p&amp;lt;0.01), while no significant changes in ES and ICD shock incidence were observed after the few LCSD procedures (n=5). A NYHA class &amp;lt;3 was associated with a trend toward a better response after BCSD (37% vs 54% incidence of ICD shock, p=0.05). Conclusions Our case series of CSD in cardiomyopathies represents the largest reported in Europe and the first ever to specifically evaluate the impact of denervation on electrical storms. The occurrence of electrical storm was more than halved by bilateral CSD confirming the powerful protective effect of BCSD also on this ominous phenomenon. The greater antiarrhythmic benefit observed among patients with better functional class suggests the opportunity to perform this procedure earlier on in the trajectory of patients with progressive heart failure.

409 PROGNOSTIC VALUE OF TENTING AREA ASSESSED BY CMR IN PATIENTS WITH ISCHEMIC MITRAL REGURGITATION

Abstract Objectives Mitral regurgitation (MR) due to complications of coronary artery disease is defined as ischemic mitral regurgitation (IMR) and, in the chronic phase after myocardial infarction (MI), it has a negative prognostic value, independently of baseline patient characteristics and degree of left ventricular (LV) dysfunction. In this context, we aimed to determine the additive prognostic role of morphological parameters, assessed by cardiac magnetic resonance (CMR), in patients with ischemic mitral regurgitation (IMR). Methods 250 patients were recruited with diagnosis of IMR, and they were divided into two groups: those with cardiac death (or appropriate ICD shocks) event at 10 years follow-up (35 patients) and those without cardiac death event (215 patients). All patients underwent CMR imaging for the assessment of left ventricular (LV) ejection fraction (EF), end-diastolic (EDV) and end-systolic volume (ESV), tenting area, tenting height, interpapillary muscles displacement and late gadolinium enhancement (LGE). Echocardiography was performed to assess MR. Results The average age of the entire sample is 64±10 years, with no significant differences between the two groups (63.2 ±10 vs 68 ±9). For what regards the echocardiographic parameters, there are no statistically significant differences in LVEDV, LVESV, SIV and PP; whereas telesystolic diameter (52 ±7 vs 42 ±9; p &amp;lt; 0,0001), telediastolic diameter (61 ±4 vs 56 ±7; p = 0,003), the EROA (0.3 ±0.09 vs 0.25 ±0.6; p &amp;lt; 0,0001) and left atrial volume (46±19 ml/m2 vs 38.7±11ml/m2 p= 0,0001) are greater in the event group. According to MRI data, patients in the event group, have significantly higher values of LVEDV (155 ±38 ml/m2 vs 111.09 ±38 ml/m2; p&amp;lt;0,001), LVESV (114.04 ±36.8 ml/m2 vs 70 ± 38; p&amp;lt;0,001), sphericity index (0.53 ±0.2 vs 0.44 ±0.1; p&amp;lt;0,001), WMSI (2 ±0.3 vs 1.75 ±0.61, p=0,02), interpapillary distance (20 ±4 vs 18.4 ±6; p&amp;lt;0,001) and posteromedial papillary muscle LGE (33% vs 16%; 0,03). Also, LVEF (28.2 ±9.03% vs 40.42 ±14.9%; p&amp;lt;0,001) is more impaired in the cardiac death event group. There is statistically significant difference between the two groups for what concerns the tenting area (3.7 ±1.4 cm2 vs 2.6 ±0.8cm2; p&amp;lt;0,001) and the tenting height (13 ±2.3 vs 10.5 ±2.6; p&amp;lt;0,001) which are higher in patients with cardiac death event. In the univariate analysis, parameters that were significantly associated with a worst prognosis are: the severe extent of mitral regurgitation (HR 4,886; 95% CI 2,198-10,861), the tenting area (HR 1,009; 95% CI 1,006-1,013), the tenting height (HR 1,295; 95% CI 1,131-1,482; p&amp;lt;0.05), the PISA radius (HR 1,329; 95% CI 1,083-1,631; p&amp;lt;0.05) the EROA (HR 511,636; 95% CI 6,932-37763,8; p&amp;lt;0.05), LGE PAP PM (HR 2,169; 95% CI 1,025-4,589; p&amp;lt;0.05) and VTDi (HR 1,012; 95% CI 1,005-1,018; p&amp;lt;0.05). In the multivariate analysis it appears that tenting area is an independent predictor (HR 1.009 IC (1.00–1.016) p&amp;lt;0.05) of negative prognosis. Conclusions Increased tenting area, assessed by CMR, has independent negative prognostic value in patients with ischemic mitral regurgitation. This finding suggests that local remodeling, which occurs in ischemic cardiomyopathy, influences the severity and the prognosis of IMR, underscoring that anatomical compromission has a preeminent role in influencing outcomes in these patients, better than functional parameters.

679 PROGNOSTIC IMPACT OF ECHOCARDIOGRAPHIC DERIVED PRECAPILLARY WEDGE PRESSURE AND PULMONARY VASCULAR RESISTANCES IN PATIENTS WITH HEART FAILURE

Abstract Background A reliable echocardiographic algorithm for the estimation of precapillary wedge pressure (PCWP) and pulmonary vascular resistances (PVR) has been recently validated by our group in a large cohort of patients undergoing right heart catheterization (RHC). Those metrics may add relevant clinical and prognostic information in patients with heart failure (HF). Objective To assess the clinical/prognostic significance of echocardiographic derived PCWP and PVR in a large cohort of chronic HF patients on modern treatments. Methods Outpatients with chronic HF with either reduced (≤40%) or mildly reduced LVEF (41-49%) underwent a thorough clinical multiparametric assessment and were followed-up for a composite endpoint of cardiac death, appropriate ICD shock, or first HF hospitalization. Results Out of 1,483 patients prospectively enrolled (70±12 years, 73% males, 42% ischemic etiology, LVEF 35±8%, 74% HFrEF), PCWP (16.4±5.8 mmHg) was elevated (&amp;gt;15 mmHg) in 53% of cases, while PVR (1.7±0.7) was elevated (&amp;gt;2 WU) in 25% of cases. Of the latter group, most (83%) had also elevated PCWP. Patients with increased PCWP were older, had a higher heart rate and lower cardiac output, showed a higher degree of left and right chamber remodeling, had a higher neurohormonal activation, worse renal function, worse functional capacity and ventilatory efficiency on effort, particularly when also PVR were elevated (all p&amp;lt;0.001). The optimal prognostic cut-point was identified for both PCWP (16.2 mmHg) and PVR (2 WU) by log-rank maximal likelihood ratio. Over a median follow-up of 27 (12-43) months, both measures significantly stratified patients for the risk of the primary endpoint at Kaplan-Meier analysis (Log Rank 99.5, p&amp;lt;0.001 for PCWP; Log Rank 18.4, p&amp;lt;0.001 for PVR). While both increased PCWP and PVR were associated with a higher risk of events in the HFrEF subgroup (both p&amp;lt;0.001), only increased PCWP significantly stratified the outcome in HFmrEF patients (Figure). At multivariable Cox regression analysis (adjusted for age, sex, ischemic HF etiology, glomerular filtrate, LVEF, and NT-proBNP), increased PCWP (hazard ratio, HR 1.67 [95%CI 1.28-2.18], p&amp;lt;0.001) but not PVR (HR 1.25 [95%CI 0.98-1.60], p=0.07) remained an independent predictor of the primary outcome. Conclusion The estimation of PCWP and PVR by echocardiography add relevant clinical and prognostic information and may help in the decision making in patients with HF.

987 VENTRICULAR TACHYCARDIA CATHETER ABLATION: THE ROLE OF ARRHYTHMIA INTERRUPTION DURING RADIOFREQUENCY EROGATION.

Abstract Background Due to the complexity of the underlying substrate and to the difficulty in characterizing the arrhythmia mechanism and circuitry, every ventricular tachycardia (VT) catheter ablation (CA) represents a challenge. Nowadays VT CA is an increasingly recommended and used procedure. Objective Investigate whether VT interruption during radiofrequency (RF) delivery can be regarded as a marker indicating a lower risk VT recurrence at follow-up. Methods We conducted a retrospective cohort study and we enrolled 69 patients with VTs treated with CA using RF energy, from November 2018 to July 2022. First, in all patient substrate and late potential map was performed; than VT induction was attempted. In patients in whom activation mapping could be performed, we first targeted VT interruption, followed by substrate modification (fragmented/late potential elimination and/or dechanneling of the entire pathologic zone) [group1]. In 15 patients, it was not possible to perform activation mapping due to the poor hemodynamic VT tolerance and/or to the absence of VT inducibility with programmed ventricular stimulation. In these cases, substrate CA was performed, aiming to eliminate fragmented and/or late potentials [group2]. Recurrences were assessed with ICD in office interrogations and remote monitoring for a median of 12 (IQR 5-20) months of follow-up. Results Sixty-nine patients were included in the study. Respectively for the group1 and for the group2, the mean age at baseline was 60 ± 18,3 and 63 ± 12,3 p &amp;gt; 0,05) and the mean left ventricular ejection fraction was 41,3 ± 12,6% and 38,2 ± 11,8% (p &amp;gt; 0,05). In 41 (59%) patients, the indication for the procedure was electrical storm refractory to pharmacological therapies or multiple ICD shocks due to VT/VF. 12 (17%) patients underwent endo-epicardial CA due to the presumed epicardial VT origin and only 9 (13%) underwent right ventricular CA. Among the 31 patients in which it was possible to interrupt the arrhythmia through RF delivery, we observed 9 (23%) sustained VT recurrence at follow-up. Among the 38 patients in which VT was not interrupted with RF delivery or the VT had poor hemodynamic tolerance, there were 16 (42%) sustained VT recurrences at follow-up. Risk of recurrence at follow-up was numerically lower in patients in which VT was interrupted with RF delivery during the procedure, but not statistically significant (p value &amp;gt; 0,05). Conclusions In patients undergoing CA for VTs, activation mapping is useful to enhance the understanding of the arrhythmia circuitry. Our preliminary results seem to suggest that VT interruption during RF delivery may represent a positive prognostic marker, pointing to better outcomes and lower recurrence rates, even if the results were not statistically significant. Further investigations with a larger cohort of patients is required to confirm these findings.

One-year results from the Assessing MICRO-vascular resistances via IMR to predict outcome in ST-elevation myocardial infarction patients with multivessel disease undergoing primary PCI (AMICRO) trial.

In ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary angioplasty (PPCI) the index of microcirculatory resistance (IMR) correlates to the extent of myocardial damage and left ventricular (LV) function recovery. Data on the IMR time-course and impact on clinical outcome in STEMI patients with multi-vessel disease (MVD) are scarce. We designed a prospective, multicenter clinical trial to assess the infarct-related artery (IRA)-IMR in STEMI patients with MVD undergoing PPCI and to explore its potential in relationship with outcome and LV remodeling. The study enrolled 242 STEMI patients with MVD. Both fractional flow reserve (FFR) and IMR of the IRA were assessed after successful PPCI. Then, FFR/IMR measurements were repeated in the IRA at a staged angiography, and FFR-guided angioplasty was performed in non-IRA lesions. The primary endpoint was the composite of cardiovascular death, re-infarction, re-hospitalization for heart failure, resuscitation or appropriate ICD shock at 1-year follow-up. A significant improvement of IRA-IMR values (from 47.9 to 34.2, p < 0.0001) was observed early after PPCI. Staged FFR-guided angioplasty was performed in 102 non-IRA lesions. We failed to find a correlation between IRA-IMR, clinical events and LV remodeling. Notwithstanding, in patients with anterior STEMI an inverse correlation between initial IMR values and LV function at follow-up was observed. After successful PPCI, a significant proportion of patients with STEMI and MVD had coronary microvascular dysfunction as assessed by IMR that recovered early after reperfusion. Higher IMR values predicted lack of improvement of LV function only in anterior STEMI. https://clinicaltrials.gov/, identifier [NCT02325973].

Programming of implantable cardioverter defibrillators for primary prevention: outcomes at centers with high vs. low concordance with guidelines.

While ICD therapy reduction programming strategies are recommended in current multi-society guidelines, concerns remain about a possible trade-off between the benefits of ICD therapy reduction and failure to treat episodes of ventricular arrhythmias. The study is to evaluate the outcomes of primary prevention patients followed in centers with high and low concordance with the 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement and 2019 focused update on optimal ICD programming and testing guidelines. Consecutive patients with primary prevention ICD implantation from two centers between 2014 and 2016 were included. One center was classified as high guideline concordance center (HGC) with 47% (146/310) of patients with initial ICD concordant with the guidelines, and the other center was classified as low guideline concordance center (LGC) with only 1% (2/178) of patients with guideline-concordant initial ICD programming. Cox proportional hazard models were used to assess risk of first ICD therapy (ATP or shock), first ICD shock, and mortality. A total of 488 patients were included (mean age, 66 ± 13years). During a mean follow-up of 1.9 ± 0.9years, patients followed at HGC were 63% less likely to receive any ICD therapy (adjusted HR [aHR] 0.37, 95% CI 0.42-0.99). There were no significant differences in the rate of first ICD shock (aHR 0.72, 95% CI 0.34-1.52) or mortality (aHR 1.19, 95% CI, 0.47-3.05). Compared to primary prevention patients followed at LGC, primary prevention ICD patients followed at HGC received a significantly lower rate of ICD therapy, mainly from ATP reduction, without a difference in mortality during follow-up.

Abstract 15045: Impact of Left Ventricular Assist Device (LVAD) Type on Arrhythmic Outcomes in Patients With Continuous Flow LVADs

Introduction: Cardiac arrhythmias are common in continuous flow left ventricular assist device (LVAD) recipients. The impact of axial vs. intrapericardial centrifugal LVAD pumps on arrhythmia incidence and associated clinical outcomes is unclear. Hypothesis: This multicenter study evaluated the impact of LVAD type (axial vs. centrifugal) on incidence of atrial and ventricular arrhythmias, ICD shocks and mortality in LVAD patients. Methods: Analysis was done on 536 patients who underwent LVAD implantation at 5 US centers from 2008 to 2016. The groups were divided based on their LVAD type (axial - HeartMate II [HMII, n=433] vs. centrifugal - HeartWare (HW, n=103). Baseline characteristics as well as incidence of post-LVAD atrial arrhythmias (PL-AA), ventricular arrhythmias (PL-VA) and ICD shocks were analyzed in these groups. Multivariable Cox Regression analysis was used to identify predictors of survival. Results: Of 536 patients, 433 had HMII axial LVAD and 103 had HW centrifugal VAD implant. At baseline, HMII group had more males, higher proportion of CRT-D and higher prevalence of AA (Table 1A). Left ventricular dimensions were similar between groups. During a median follow-up of 537 days of LVAD support, incidence of PL-VA and ICD shocks were significantly higher in the HM2 group compared to HW group whereas incidence of PL-AA was not significantly different (Table 1A). In multivariable Cox Regression analysis, LVAD indication was the only variable that predicted survival (Table 1B). Type of LVAD (axial vs. centrifugal) was not associated with survival (HMII vs. HW - HR 1.04, P=0.48). Conclusions: In this multi-center continuous flow LVAD cohort, axial HM2 VAD patients had a higher incidence of PL-VA and ICD shocks. Type of LVAD (axial vs. centrifugal) was not associated with survival.

Abstract 13141: Age of Onset and Clinical Outcomes in RBM20 -Mediated Arrhythmogenic Dilated Cardiomyopathy

Introduction: Pathogenic loss-of-function variants in the RBM20 -encoded RNA-binding motif 20 splicing regulator cause a severe form of arrhythmogenic dilated cardiomyopathy (DCM). Erroneous splicing of TTN -encoded titin contributes to the pathogenesis of RBM20 -mediated disease. However, studies exploring the clinical course of RBM20 -mediated arrhythmogenic DCM alone or in comparison to TTN -mediated DCM, the most common familial cause of DCM, are lacking. Methods: The Mayo Clinic Genetic Arrhythmogenic Cardiomyopathy Registry (n=391) was used to identify all patients with a pathogenic/likely pathogenic (P/LP) variant in either RBM20 or TTN . For the purposes of this study, a ventricular arrhythmia (VA) event was defined as sudden cardiac arrest, sustained ventricular arrhythmia, or an appropriate ICD shock and an advanced heart failure (AHF) event was defined as ventricular assist device implantation or heart transplantation. Results: Overall, 40 patients with a P/LP variant in RBM20 (50% female) and 70 patients with a P/LP variant in TTN (43% female) were identified. The prevalence of a cardiac phenotype in patients with RBM20- and TTN -mediated disease was 88% and 83%, respectively. RBM20 patients were more likely to have a family history of sudden cardiac arrest (78% vs 34%; p &lt; 0.0001) and cardiomyopathy (90% vs 61%; p=0.001). No difference in rate of ICD implantation (35% versus 33%) was observed. Interestingly, the prevalence of AHF events (10% vs 6%; p=0.5) and VA events (28% vs 24%; p=0.7) was similar between RBM20 - and TTN -positive patients. However, RBM20 patients were younger than TTN patients at the time of their event (37 ± 18 years vs 50 ± 17; p=0.0004). Time-to-event analysis showed RBM20 patients had an earlier time to AHF event (p=0.05) and time to VA event (p=0.03) than TTN patients. The mean age for AHF events was 25 years for RBM20 patients (N=4) and 47 years for TTN patients (N=4). The mean age for VA events was 29 years for RBM20 patients (N=10) and 42 years for TTN patients (N=14). Conclusions: RBM20 -mediated arrhythmogenic DCM represents a highly penetrant genetic heart disease with potentially life-threatening VAs and end stage heart failure manifestations occurring at a significantly younger age in comparison to TTN -mediated DCM.

Abstract 9457: Primary Cardiac Allograft Dysfunction Caused by Pretransplantation Amiodarone Therapy

Background: Primary graft dysfunction (PGD) is devastating. Amiodarone therapy prior to cardiac transplantation (TxP) is common but has recently been reported as potential cause of PGD. Case: 66-year-old male with non-ischemic cardiomyopathy, severely reduced LVEF with LVAD, recurrent VT on amiodarone for 6 months presented with ICD shocks. Amiodarone was increased due to VT storm in the setting of Rhinovirus infection. Infusions with amiodarone and lidocaine were started but repeat IV boli of lidocaine and amiodarone were needed. VT-ablation was not feasible due to multiple morphologies. He underwent TxP with an ideal organ from a 28 yo donor. Paragonix SherpaPak was used for transport. Pre-explanation EF was 70% with serologies positive for EBV (+/+), Strongyloides (+/-), negative for Toxoplasmosis (-/-), CMV (-/-). Donor heart was arrested with appropriate cardioplegia and no distention occurred. Total ischemic time was 3 hours 10 minutes, warm ischemic time 40 minutes, crossclamp time in recipient 2 hours 2 minutes with total cardiopulmonary bypass time 2 hours 58 minutes. Coming off bypass both ventricles appeared markedly dilated with severely reduced function and due to high doses of inotropic and vasopressor support veno-arterial ECMO was placed. The chest was left open and during postoperative course in the intensive care unit pressor and inotropes could slowly weaned. Induction therapy was administered with ATG, Solumedrol and mycophenolate mofetil. Strongyloides infection was treated with four doses of Ivermectin. On postoperative day LVEF recovered to 40-45% with moderately reduced RV function and patient was successfully decannulated from VA ECMO with chest closure. Endomyocardial biopsies showed no signs of rejection throughout. After prolonged ICU and rehab stay patient has now recovered to independent life. Conclusion: Amiodarone associated PGD may be underreported and increasing awareness of this etiology may warrant early empiric discontinuation of the medication if transplantation remains a therapeutic option in the future.