Non-ischemic Cardiomyopathy Patients Research Articles

Pre- and Post-Procedural Cardiac Imaging (CT and MRI) in Electrophysiology: A Clinical Consensus Statement of the European Heart Rhythm Association (EHRA) and European Association of Cardiovascular Imaging (EACVI) of the ESC.

Imaging using cardiac computed tomography (CT) or magnetic resonance imaging (MR) has become an important option for anatomic and substrate delineation in complex atrial and ventricular tachycardia (VT) ablation procedures. CT more common than MR has been used to detect procedure-associated complications like esophageal, cerebral and vascular injury. This clinical consensus statement summarizes the current knowledge of CT and MR to facilitate electrophysiological procedures, the current value of real-time integration of imaging-derived anatomy and substrate information during the procedure and the current role of CT and MR in diagnosing relevant procedure-related complications. Practical advice on potential advantages of one imaging modality over the other is discussed for patients with implanted cardiac rhythm devices as well as for planning, intraprocedural integration and post-interventional management in atrial fibrillation (AF) and VT ablation patients. Establishing a team of electrophysiologists and cardiac-imaging specialists working on specific details of imaging for complex ablation procedures is key. CMR can safely be performed in most patients with implanted active cardiac devices. Standard procedures for pre- and post-scanning management of the device and potential CMR-associated device-malfunctions need to be in place. In VT patients imaging - specifically MR - may help to determine scar location and mural distribution in ischemic and non-ischemic cardiomyopathy patients beyond evaluating the underlying structural heart disease. Future directions in imaging may include the ability to register multiple imaging modalities, novel high-resolution modalities but also refinements of imaging-guided ablation strategies are expected.

Lipomatous Metaplasia Is Associated With Ventricular Tachycardia Recurrence Following Ablation in Patients With Nonischemic Cardiomyopathy.

Ventricular tachycardia (VT) recurrence rates remain high following ablation among patients with nonischemic cardiomyopathy (NICM). This study sought to define the prevalence of lipomatous metaplasia (LM) in patients with NICM and VT and its association with postablation VT recurrence. From patients who had ablation of left ventricular VT, we retrospectively identified 113 consecutive NICM patients with preprocedural contrast-enhanced cardiac computed tomography (CECT), from which LM was segmented. Nested within this cohort were 62 patients that prospectively underwent CECT and cardiac magnetic resonance from which myocardial border zone and dense late gadolinium enhancement (LGE) were segmented. A control arm of 30 NICM patients without VT with CECT was identified. LM was identified among 57% of control patients without VT vs 83% of patients without VT recurrence and 100% of patients with VT recurrence following ablation. In multivariable analyses, LM extent was the only independent predictor of VT recurrence, with an adjusted HR per 1-g LM increase of 1.1 (P< 0.001). Patients with LM extent≥2.5g had 4.9-fold higher hazard of VT recurrence than those with LM<2.5g (P< 0.001). In the nested cohort with 32 VT recurrences, LM extent was independently associated with VT recurrence after adjustment for border zone and LGE extent (HR per 1g increase: 1.1; P = 0.036). Myocardial LM is prevalent in patients with NICM of a variety of etiologies, and its extent is associated with postablation VT recurrence independent of the degree of fibrosis.

A Comparison of the Association of Septal Scar Burden on Responses to LBBAP-CRT and BVP-CRT.

Left bundle branch area pacing (LBBAP) is an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). However, despite the presence of left bundle branch block, whether cardiac substrate may influence the effect between the 2 strategies is unclear. This study aims to assess the association of septal scar on reverse remodeling and clinical outcomes of LBBAP compared with BVP. We analyzed patients with nonischemic cardiomyopathy who had CRT indications undergoing preprocedure cardiac magnetic resonance examination. Changes in left ventricular ejection fraction (LVEF) and echocardiographic response (ER,≥5% absolute LVEF increase) were assessed at 6months. The clinical outcome was the composite of all-cause mortality, heart failure hospitalization, or major ventricular arrhythmia. There were 147 patients included (51 LBBAP and 96 BVP). Among patients with low septal scar burden (below median 5.7%, range: 0 to 5.3%), LVEF improvement was higher in the LBBAP than the BVP group (17.5% ± 10.9% vs 12.3% ± 11.8%; P=0.037), with more than 3-fold increased odds of ER (odds ratio: 4.35; P=0.033). In high sepal scar subgroups (≥5.7%, range: 5.7% to 65.9%), BVP trended towards higher LVEF improvement (9.2% ± 9.4% vs 6.4% ± 12.4%; P=0.085). Interaction between septal scar burden and pacing strategy was significant for ER (P=0.002) and LVEF improvement (P=0.011) after propensity score adjustment. During median follow-up of 33.7 (Q1-Q3: 19.8 to 42.1) months, the composite clinical outcome occurred in 34.7% (n=51) of patients. The high-burden subgroups had worse clinical outcomes independent of CRT method. Remodeling response to LBBAP and BVP among nonischemic cardiomyopathy patients is modified by septal scar burden. High septal scar burden was associated with poor clinical prognosis independent of CRT methods.

Rate of Change of Initial Intrinsicoid Deflection Predicts Endocardial Versus Epicardial Ventricular Tachycardia

Rate of Change of Initial Intrinsicoid Deflection Predicts Endocardial Versus Epicardial Ventricular Tachycardia

Assessment of ICD eligibility in non-ischaemic cardiomyopathy patients: aposition statement by the Task Force of the Dutch Society of Cardiology.

International guidelines recommend implantation of an implantable cardioverter-defibrillator (ICD) in non-ischaemic cardiomyopathy (NICM) patients with aleft ventricular ejection fraction (LVEF) below 35% despite optimal medical therapy and alife expectancy of more than 1year with good functional status. We propose refinement of these recommendations in patients with NICM, with careful consideration of additional risk parameters for both arrhythmic and non-arrhythmic death. These additional parameters include late gadolinium enhancement on cardiac magnetic resonance imaging and genetic testing for high-risk genetic variants to further assess arrhythmic risk, and age, comorbidities and sex for assessment of non-arrhythmic mortality risk. Moreover, several risk modifiers should be taken into account, such as concomitant arrhythmias that may affect LVEF (atrial fibrillation, premature ventricular beats) and resynchronisation therapy. Even though currently no valid cut-off values have been established, the proposed approach provides amore careful consideration of risks that may result in withholding ICD implantation in patients with low arrhythmic risk and substantial non-arrhythmic mortality risk.

Outcomes of ventricular tachycardia ablation in patients with ischemic and non-ischemic cardiomyopathy: A propensity-score matched analysis

Introduction and objectivesCatheter ablation (CA) is effective in the treatment of ventricular tachycardia (VT). Although some observational data suggest patients with non-ischemic cardiomyopathy (NICM) have less favorable outcomes when compared to those with an ischemic etiology (ICM), direct comparisons are rarely reported. We aimed to compare the outcomes of VT ablation in a propensity-score matched population of ICM or NICM patients. MethodsSingle-center retrospective study of consecutive patients undergoing VT ablation from 2012 to 2023. A propensity score (PS) was used to match ICM and NICM patients in a 1:1 fashion according to age, sex, left ventricular ejection fraction (LVEF), NYHA class, electrical storm (ES) at presentation, and previous endocardial ablation. The outcomes of interest were VT-free survival and all-cause mortality. ResultsThe PS yielded two groups of 71 patients each (mean age 63±10 years, 92% male, mean LVEF 35±10%, 36% with ES at presentation, and 23% with previous ablation), well matched for baseline characteristics. During a median follow-up of 2.3 (interquartile range IQR 1.3–3.8) years, patients with NICM had a significantly lower VT-free survival (53.5% vs. 69.0%, log-rank p=0.037), although there were no differences regarding all-cause mortality (22.5% vs. 16.9%, log-rank p=0.245). Multivariate analysis identified NICM (HR 2.34 [95% CI 1.32–4.14], p=0.004), NYHA class III/IV (HR 2.11 [95% CI 1.11–4.04], p=0.024), and chronic kidney disease (HR 2.23 [95% CI 1.25–3.96], p=0.006), as independent predictors of VT recurrence. ConclusionNon-ischemic cardiomyopathy patients were at increased risk of VT recurrence after ablation, although long-term mortality did not differ.

Fibrosis modeling choice affects morphology of ventricular arrhythmia in non-ischemic cardiomyopathy.

Introduction: Patients with non-ischemic cardiomyopathy (NICM) are at risk for ventricular arrhythmias, but diagnosis and treatment planning remain a serious clinical challenge. Although computational modeling has provided valuable insight into arrhythmic mechanisms, the optimal method for simulating reentry in NICM patients with structural disease is unknown. Methods: Here, we compare the effects of fibrotic representation on both reentry initiation and reentry morphology in patient-specific cardiac models. We investigate models with heterogeneous networks of non-conducting structures (cleft models) and models where fibrosis is represented as a dense core with a surrounding border zone (non-cleft models). Using segmented cardiac magnetic resonance with late gadolinium enhancement (LGE) of five NICM patients, we created 185 3D ventricular electrophysiological models with different fibrotic representations (clefts, reduced conductivity and ionic remodeling). Results: Reentry was induced by electrical pacing in 647 out of 3,145 simulations. Both cleft and non-cleft models can give rise to double-loop reentries meandering through fibrotic regions (Type 1-reentry). When accounting for fibrotic volume, the initiation sites of these reentries are associated with high local fibrotic density (mean LGE in cleft models: p 0.001, core volume in non-cleft models: p = 0.018, negative binomial regression). In non-cleft models, Type 1-reentries required slow conduction in core tissue (non-cleftsc models) as opposed to total conduction block. Incorporating ionic remodeling in fibrotic regions can give rise to single- or double-loop rotors close to healthy-fibrotic interfaces (Type 2-reentry). Increasing the cleft density or core-to-border zone ratio in cleft and non-cleftc models, respectively, leads to increased inducibility and a change in reentry morphology from Type 2 to Type 1. Conclusions: By demonstrating how fibrotic representation affects reentry morphology and location, our findings can aid model selection for simulating arrhythmogenesis in NICM.

Long-term efficacy of left bundle branch pacing and biventricular pacing in patients with heart failure complicated with left bundle branch block.

Left bundle branch pacing (LBBP) can physiologically correct complete left bundle branch block (CLBBB), and has become the best alternative to biventricular pacing (BiVP). To compare the efficacy of LBBP and BiVP in patients with heart failure (HF) complicated with CLBBB. This was a single-center retrospective study. Patients with HF complicated with CLBBB who underwent successful cardiac resynchronization therapy (CRT) in Wuhan Asian Heart Hospital from June 2018 to June 2023 were enrolled and divided into LBBP group and BiVP group according to the pacing method. The primary endpoints were the absolute increase of left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and echocardiographic response rate. Secondary endpoints were all-cause mortality, heart failure hospitalization (HFH), NT-proBNP, paced QRS duration, pacing threshold, and procedural duration. A total of 120 patients were enrolled in this study, including 60 patients in LBBP group and 60 patients in BiVP group. The median follow-up time was 37 ± 19 months. Compared with BiVP group, LBBP group had a more significant increase in absolute LVEF (ΔLVEF) (14.8 ± 9.9% vs. 10.7 ± 9.0%, P = 0.02), a more significant reduction in LVEDD (56.9 ± 10.9 mm vs. 61.1 ± 10.8 mm, P = 0.03), and a higher echocardiographic super response rate (65% vs. 45%, P = 0.02). There were no significant differences in all-cause mortality (1.7% vs. 10.0%, P = 0.11) and HFH (6.7% vs. 13.3%, P = 0.22). In terms of paced QRS duration (128.7 ± 14.1 ms vs. 137.5 ± 16.5 ms, P = 0.002), pacing threshold (0.72 ± 0.21 V/0.4 ms vs. 1.39 ± 0.51 V/0.4 ms, P < 0.001), procedural duration (134.1 ± 32.2 min vs. 147.7 ± 39.4 min, P = 0.04), the LBBP group was superior to the BiVP group. In nonischemic cardiomyopathy (NICM) patients with HF combined with CLBBB and LVEF ≤ 35%, LBBP is better than BiVP.

MRI Assessment of Myocardial Deformation for Risk Stratification of Major Arrhythmic Events in Patients With Non-Ischemic Cardiomyopathy Eligible for Primary Prevention Implantable Cardioverter Defibrillators.

Implantable cardioverter-defibrillator (ICD) intervention is an established prophylactic measure. Identifying high-benefit patients poses challenges. To assess the prognostic value of cardiac magnetic resonance imaging (MRI) parameters including myocardial deformation for risk stratification of ICD intervention in non-ischemic cardiomyopathy (NICM) while accounting for competing mortality risk. Retrospective and prospective. One hundred and fifty-nine NICM patients eligible for primary ICD (117 male, 54 ± 13 years) and 49 control subjects (38 male, 53 ± 5 years). Balanced steady state free precession (bSSFP) and three-dimensional phase-sensitive inversion-recovery late gadolinium enhancement (LGE) sequences at 1.5 T or 3 T. Patients underwent MRI before ICD implantation and were followed up. Functional parameters, left ventricular global radial, circumferential and longitudinal strain, right ventricular free wall longitudinal strain (RV FWLS) and left atrial strain were measured (Circle, cvi42). LGE presence was assessed visually. The primary endpoint was appropriate ICD intervention. Models were developed to determine outcome, with and without accounting for competing risk (non-sudden cardiac death), and compared to a baseline model including LGE and clinical features. Wilcoxon non-parametric test, Cox's proportional hazards regression, Fine-Gray competing risk model, and cumulative incidence functions. Harrell's c statistic was used for model selection. A P value <0.05 was considered statistically significant. Follow-up duration was 1176 ± 960 days (median: 896). Twenty-six patients (16%) met the primary endpoint. RV FWLS demonstrated a significant difference between patients with and without events (-12.5% ± 5 vs. -16.4% ± 5.5). Univariable analyses showed LGE and RV FWLS were significantly associated with outcome (LGE: hazard ratio [HR] = 3.69, 95% CI = 1.28-10.62; RV FWLS: HR = 2.04, 95% CI = 1.30-3.22). RV FWLS significantly improved the prognostic value of baseline model and remained significant in multivariable analysis, accounting for competing risk (HR = 1.73, 95% CI = 1.12-2.66). In NICM, RV FWLS may provide additional predictive value for predicting appropriate ICD intervention. 2 TECHNICAL EFFICACY: Stage 5.

Differences in underlying cardiac substrate among S-ICD recipients and its impact on long-term device-related outcomes: Real-world insights from the iSUSI registry

BackgroundOutcome comparisons among subcutaneous implantable cardioverter-defibrillator (S-ICD) recipients with nonischemic cardiomyopathies are scarce. ObjectiveThe aim of this study was to evaluate differences in device-related outcomes among S-ICD recipients with different structural substrates. MethodsPatients enrolled in the i-SUSI (International SUbcutaneouS Implantable cardioverter defibrillator registry) project were grouped according to the underlying substrate (ischemic vs nonischemic) and subgrouped into dilated cardiomyopathy, hypertrophic cardiomyopathy, Brugada syndrome (BrS), arrhythmogenic right ventricular cardiomyopathy (ARVC). The main outcome of our study was to compare the rates of appropriate and inappropriate shocks and device-related complications. ResultsAmong 1698 patients, the most common underlying substrate was ischemic (31.7%), followed by dilated cardiomyopathy (20.5%), BrS (10.8%), hypertrophic cardiomyopathy (8.5%), and ARVC (4.4%). S-ICD for primary prevention was more common in the nonischemic cohort (70.9% vs 65.4%; P = .037). Over a median (interquartile range) follow-up of 26.5 (12.6–42.8) months, no differences were observed in appropriate shocks between ischemic and nonischemic patients (4.8%/y vs 3.9%/y; log-rank, P = .282). ARVC (9.0%/y; hazard ratio [HR] 2.492; P = .001) and BrS (1.8%/y; HR 0.396; P = .008) constituted the groups with the highest and lowest rates of appropriate shocks, respectively. Device-related complications did not differ between groups (ischemic: 6.4%/y vs nonischemic: 6.1%/y; log-rank, P = .666), nor among underlying substrates (log-rank, P = .089). Nonischemic patients experienced higher rates of inappropriate shocks than did ischemic S-ICD recipients (4.4%/y vs 3.0%/y; log-rank, P = .043), with patients with ARVC (9.9%/y; P = .001) having the highest risk, even after controlling for confounders (adjusted HR 2.243; confidence interval 1.338–4.267; P = .002). ConclusionMost S-ICD recipients were primary prevention nonischemic cardiomyopathy patients. Among those, patients with ARVC tend to receive the most frequent appropriate and inappropriate shocks and patients with BrS the least frequent appropriate shocks.

Liver T1 Mapping Derived From Cardiac Magnetic Resonance Imaging: A Potential Prognostic Marker in Idiopathic Dilated Cardiomyopathy.

Hepatic alterations are common aftereffects of heart failure (HF) and ventricular dysfunction. The prognostic value of liver injury markers derived from cardiac MRI studies in nonischemic dilated cardiomyopathy (DCM) patients is unclear. Evaluate the prognostic performance of liver injury markers derived from cardiac MRI studies in DCM patients. Prospective. Three hundred fifty-six consecutive DCM patients diagnosed according to ESC guidelines (age 48.7 ± 14.2 years, males 72.6%). Steady-state free precession, modified Look-Locker inversion recovery T1 mapping and phase sensitive inversion recovery late gadolinium enhancement (LGE) sequences at 3 T. Clinical characteristics, conventional MRI parameters (ventricular volumes, function, mass), native myocardial and liver T1, liver extracellular volume (ECV), and myocardial LGE presence were assessed. Patients were followed up for a median duration of 48.3 months (interquartile range 42.0-69.9 months). Primary endpoints included HF death, sudden cardiac death, heart transplantation, and HF readmission; secondary endpoints included HF death, sudden cardiac death, and heart transplantation. Models were developed to predict endpoints and the incremental value of including liver parameters assessed. Optimal cut-off value was determined using receiver operating characteristic curve and Youden method. Survival analysis was performed using Kaplan-Meier and Cox proportional hazard. Discriminative power of models was compared using net reclassification improvement and integrated discriminatory index. P value <0.05 was considered statistically significant. 47.2% patients reached primary endpoints; 25.8% patients reached secondary endpoints. Patients with elevated liver ECV (cut-off 34.4%) had significantly higher risk reaching primary and secondary endpoints. Cox regression showed liver ECV was an independent prognostic predictor, and showed independent prognostic value for primary endpoints and long-term HF readmission compared to conventional clinical and cardiac MRI parameters. Liver ECV is an independent prognostic predictor and may serve as an innovative approach for risk stratification for DCM. 1 TECHNICAL EFFICACY: Stage 2.

VT ablation based on CT imaging substrate visualization: results from a large cohort of ischemic and non-ischemic cardiomyopathy patients.

The eradication of ventricular tachycardia (VT) isthmus sites constitutes the minimal procedural endpoint for VT ablation procedures. Contemporary high-resolution computed tomography (CT) imaging, in combination with computer-assisted analysis and segmentation of CT data, facilitates targeted elimination of VT isthmi. In this context, inHEART offers digitally rendered three-dimensional (3D) cardiac models which allow preoperative planning for VT ablations in ischemic and non-ischemic cardiomyopathies. To date, almost no data have been collected to compare the outcomes of VT ablations utilizing inHEART with those of traditional ablation approaches. The presented data are derived from a retrospective analysis of n = 108 patients, with one cohort undergoing VT ablation aided by late-enhancement CT and subsequent analysis and segmentation by inHEART, while the other cohort received ablation through conventional methods like substrate mapping and activation mapping. The ablations were executed utilizing a 3D mapping system (Carto3), with the mapping generated via the CARTO® PENTARAY™ NAV catheter and subsequently merged with the inHEART model, if available. Results showed more successful outcome of ablations for the inHEART group with lower VT recurrence (27% vs. 42%, p < 0.06). Subsequent analyses revealed that patients with ischemic cardiomyopathies appeared to derive a significant benefit from inHEART-assisted VT ablation procedures, with a higher rate of successful ablation (p = 0.05). Our findings indicate that inHEART-guided ablation is associated with reduced VT recurrence compared to conventional procedures. This suggests that employing advanced imaging and computational modeling in VT ablation may be valuable for VT recurrences.

Incidence of sustained ventricular tachyarrhythmias in patients with non-ischemic cardiomyopathy in a multicenter multinational WCD cohort

Abstract Background Defibrillator use in patients with non-ischemic cardiomyopathy (NICM) and HFrEF remains controversial after the DANISH study. The new ESC guidelines recommend individualized risk stratification in these patients. The wearable cardioverter-defibrillator (WCD) seems to be appropriate to both protect and screen patients with HFrEF at risk for sudden cardiac death (SCD). Puropose: To evaluate the rate of ventricular tachyarrhythmias (VT/VF) in NICM vs. ICM patients receiving a WCD for temporary SCD protection. Methods 1157 patients were included in a multicenter registry from eight European centers. Among these patients, 602 patients received a WCD due to ischemic cardiomyopathy (ICM) and 555 patients for non-ischemic cardiomyopathy (NICM). Incidence of VT/VF and/or appropriate WCD shock discharge during WCD use were evaluated. The mean follow-up (FU) time of the whole cohort was 620.2±607.8 days. Results NICM patients were younger (mean 56.5±14.8a vs 63.9±11.6a; p&amp;lt;0.001) and less often male (75% vs. 87.2%; p&amp;lt;0.001) compared to ICM patients. Heart failure medication at hospital discharge did not differ between the two groups except for a higher prescription rate of aldosterone-antagonists in NICM compared to ICM patients (73.8% vs. 66.7%; p=0.02). The index left ventricular ejection fraction (LVEF) was significantly lower in NICM compared to ICM patients (mean 26.1±9.1% versus 29.5±9.2%; p&amp;lt;0.001). A larger extent of LVEF recovery was detected in NICM patients compared to ICM patients up to the end of WCD use (mean LVEF post WCD: 45.7±35.4% vs. 40.2±11.8%; p=0.02). Average daily WCD wear-time was significantly lower in NICM patients compared to ICM patients (mean 20.7±4.9h vs. 21.6±3.7h; p=0.01). NICM patients had a significantly lower incidence of sustained ventricular tachyarrhythmia (VT/VF) compared to ICM patients (3.4% vs. 6.6%; p=0.02). Consistently, rate of appropriate WCD shock was significantly lower in NICM vs. ICM patients (0.7% vs. 3.7%; p&amp;lt; 0.001), as was rate of re-hospitalization (30.2% vs. 46.1%; p&amp;lt;0.001). Both groups showed a similar mortality rate during FU. Conclusions Patients at risk for SCD with NICM showed a more pronounced LVEF recovery, significantly lower incidence of VT/VF with concomitant shocks and hospitalization, while overall mortality was unchanged compared to ICM patients. These results indicate that WCD use might facilitate individual SCD risk stratification in NICM patients.

Two-year outcomes of primary prophylactic use of defibrillators with ischemic and non-ischemic cardiomyopathy: propensity score-matched analysis from NIPPON STORM Study

Abstract Background In 2016, the DANISH study showed negative results regarding the efficacy of implantable cardioverter defibrillators (ICDs) for patients with non-ischemic cardiomyopathy (NICM) and reduced left ventricular ejection fraction (LVEF). Thus, the ESC guidelines downgraded the indication for primary ICD prophylaxis for NICM patients with reduced LVEF from Class I to IIa. However, the change might be felt somewhat improper in the real wolrd ICD therapy and decided to use the Nippon storm study, a prospective registry study in Japan, to determine whether the DANISH results are of equal value in the clinical setting. Objective To determine the efficacy of ICDs as primary prevention in patients with NICM, the incidence of ICD appropriate therapy in patients with NICM was compared with that in patients with ischemic cardiomyopathy (ICM) for which primary ICD efficacy is generally recognized as a Class I indication. Methods We selected 1274 patients with underlying cardiac disease from a total of 1548 patients enrolled in the Nippon storm study. We analyzed data of 451 patients with LVEF ≤35% owing to NICM or ICM who underwent ICD implantation of primary prophylaxis (men, 78%; age, 65±12 years; LVEF, 25±1.4%; cardiac resynchronization therapy, 20%; ICM, 33%). All patients were followed up for at least 2 years. Patient selection was performed by employing the propensity score matching method with a digit-matching algorithm for clinical factors, ie, age, sex, cardiac resynchronization therapy with a defibrillator, LVEF. After all propensity score matches had been performed, we compared baseline covariates between the 2 groups: 132 patients with NICM and 132 with ICM. The cumulative incidences of ICD therapies (including both anti-tachycardia pacing and shock therapies) were calculated using competing risk analysis, because death is a competing risk for loss to follow-up. Results In the matched cohort, the 2-year appropriate ICD therapy risks were 27.7% and 12.2% in NICM and ICM groups, respectively (HR = 0.390 [95% CI, 0.218–0.701; P = 0.002) (Figure A). Two-year appropriate ATP therapy risks were 25.5% and 11.4% in NICM and ICM groups, respectively (HR = 0.417 [95% CI, 0.226– 0.776; P = .005]) (Figure B), and appropriate shock therapy risks were 6.3% and 1.6% in NICM and ICM groups, respectively (HR = 0.230 [95% CI, 0.049–1.085; P = .063]) (Figure C). Conclusion The present subanalysis of the Nippon Storm Study revealed that the risk for appropriate ICD therapy was significantly higher in the patients with NICM than in those with ICM based on our propensity score–matching method.

Abstract 12905: Epicardial and Intramyocardial Fat as Predictors of Ventricular Arrhythmia in Ischemic and Non-Ischemic Cardiomyopathy

Background: Sudden cardiac death from ventricular arrhythmia (VA) is a global concern. While emerging evidence suggests a role for myocardial fat in the development of VA among ischemic (ICM) and non-ischemic cardiomyopathy (NICM) patients, the volume and distribution of epicardial adipose tissue (EAT) and intramyocardial fat (IMF) linked to VA remain underexplored. Objective: To evaluate the predictive value of LV tissue heterogeneity, EAT, and IMF volumes in assessing the risk of VA in ICM and NICM patients. Methods: Patients enrolled in the PROSE-ICD registry, who underwent contrast-enhanced computed tomography were included. The designated endpoint was ventricular arrhythmia, defined as appropriate ICD shock or sudden arrhythmic death. IMF volume (voxels between -180 and -5 HU), EAT volume (voxels between -200 to -50 HU), and myocardial fat tissue heterogeneity (defined as the magnitude of change between nearby voxels) were calculated. Logistic regression models were employed to assess the association between explanatory variables and outcome. Results: 98 patients (47 ICM, 51 NICM) were included with a mean follow up time of 5.6±3.4 years. Participants’ mean age was 56±13.2 years, and 66% were male. LV tissue heterogeneity (per HU/mm) was associated with VA incidence (OR = 1.11; P &lt; 0.01) in the ICM cohort, whereas EAT and IMF volume were associated with VA in the NICM subgroup [(OR = 1.12; P &lt; 0.01), and (OR = 1.21; P = 0.01), respectively]. Even after adjusting for various covariates, LV tissue heterogeneity in the ICM group and EAT in the NICM group maintained a significant association with VA. Conclusion: In ICM, increased fat distribution heterogeneity is associated with VA, while in NICM, increased IMF and EAT volume are linked to a higher risk for VA. These findings suggest that LV tissue heterogeneity and EAT volume offer valuable prognostic insights in cardiomyopathy patients, indicating that the contribution of fat to VA depends on the underlying substrate.

Abstract 12377: Differing Response to Left Bundle Branch Area Pacing versus Biventricular Pacing for Cardiac Resynchronization According to Septal Scar Burden Among Nonischemic Cardiomyopathy Patients

Introduction: Whether left bundle branch area pacing (LBBAP) have similar benefit compared with biventricular pacing (BVP) for cardiac resynchronization therapy (CRT) in nonischemic cardiomyopathy (NICM) with different septal scar burden is still unknown. Hypothesis: We hypothesize that a higher septal scar burden might attenuate the relative benefits of LBBAP versus BVP. Aims: This study aims to assess the effect of the septal scar on the response to LBBAP and BVP for CRT. Methods: We retrospectively included nonischemic cardiomyopathy (NICM) patients with wide QRS complex and CRT indications who underwent pre-procedure cardiac magnetic resonance (CMR) examination and received either BVP or LBBAP. Late gadolinium enhancement (LGE) was analyzed for scar quantification. CRT response was defined as an absolute increase of≥ 5% in left ventricular ejection fraction (LVEF) at 6 months follow-up. Results: A total of 147 patients were included. Fifty-one patients (34.7%) had LBBAP, and 96 (65.3%) had BVP. As septal LGE extent increased, LVEF improvement at 6-month follow-up gradually decreased in the BVP group whereas dropped sharply in the LBBAP group. The nonlinear inverse relationship between the relative benefit of LBBAP versus BVP for response and septal LGE extent, as well as cut-off points (4.4%, 13.3%) of septal LGE extent, were determined using a restricted cubic spline model. Among patients with low septal scar extent (&lt;4.4%), LBBAP was associated with higher response odds than BVP [Odds Ratio (OR) 3.87,95% confidence interval (CI): 0.99-15.17,p=0.052]. In the medium septal scar extent (4.4%-13.3%) group, response odds did not differ between LBBAP and BVP (OR 2.00,95%CI: 0.41-9.74, p=0.391). Among patients with high septal scar extent (&gt;13.3%), BVP was associated with higher response odds (OR 0.12, 95%CI: 0.03-0.54, p=0.006). Conclusions: Response to LBBAP and BVP among NICM patients might be impacted by septal scar burden.

Abstract 16938: Epicardial Adipose Tissue on the Risk of Lethal Ventricular Arrhythmias in Patients With Nonischemic Cardiomyopathy Receiving Implantable Cardioverter-Defibrillator

Background: The arrhythmic risk stratification in patients with nonischemic cardiomyopathy (NICM) remains challenging. The implication of epicardial adipose tissue (EAT) on incident sudden cardiac death (SCD) is unclear. Objectives: To assess the relationship between EAT and SCD in NICM patients receiving implantable cardioverter-defibrillators (ICD) and compare this risk to patients with ischemic cardiomyopathy (ICM). Methods: A total of 421 patients scheduled for primary or secondary prevention ICD implantation underwent CMR at 1.5 or 3T, including cine and late gadolinium enhancement (LGE) imaging. EAT volume surrounding both ventricles was quantified with manual delineation on cine short-axis images and calculated by summation of EAT volume of each slice using the modified Simpson rule. LGE was semiautomatically quantified by adjusting a grayscale threshold. The primary endpoint was a composite of ICD therapy, including anti-tachycardia pacing and SCD. Results: We identified 265 NICM patients (mean age 54 years, 73% men), with LGE present in 152 patients (57%), including 85 patients (32%) with secondary prevention ICD. During the median follow-up of 2.9 years, 42 patients (16%) experienced the endpoint. Low EAT was associated with an increased risk of SCD in NICM patients (HR ad per 10ml decrease, 1.54; 95%CI, 1.19-1.96, p&lt;0.001), even after adjustment for other relevant disease variables. A continuous relationship was evident between EAT and subsequent ICD therapies (p=0.001). Even when considering 85 patients with secondary prevention ICD as theoretically having an SCD event, the risk of EAT in predicting SCD remained essentially unchanged. In contrast, EAT was not associated with increased SCD risk in ICM patients. Conclusions: Low EAT was associated with increased SCD risk in NICM patients receiving ICD implantation, especially primary prevention ICD. These data suggest a potential role of EAT in identifying NICM patients at risk of SCD.

Abstract 12761: Pathogenic Genetic Variants in Patients With Heart Transplant Due to Ischemic and Non-Ischemic Cardiomyopathy

Introduction: Current clinical guidelines recommend offering genetic testing to all patients diagnosed with non-ischemic cardiomyopathy (NICM), particularly in patients with a strong family history. The utility of genetic testing more broadly in patients with end-stage heart failure requiring heart transplant (HT) is unknown. Hypothesis: Among patients with HT, prevalence of cardiovascular disease (CVD)-associated pathogenic/likely pathogenic (P/LP) variants is higher in those with NICM than those with ischemic cardiomyopathy (ICM). Methods: We performed targeted DNA sequencing of 120 mendelian CVD genes in 124 consented patients with a HT, enrolled in the Vanderbilt Cardiac Catheterization Lab Cohort between 2003 and 2021. DNA sequence variation was annotated as P/LP based on ACMG criteria. Results: Out of 124 participants with HT, 70 had NICM and 51 had ICM. 22.8% of the NICM group harbored a P/LP variant in TTN (n=5), LMNA (5), MYH7 (1), RYR2 (1), RBM20 (1), COL1A2 (1), PKP2 (1), and CASQ2 (1). 19.6% of ICM participants harbored a P/LP variant in LDLR (2), RYR2 (1), TTN (1), SDHA (1), MYH7 (1), SGCD (1), MYL3 (1), CASQ2 (1), and COL1A2 (1). In NICM and ICM patients with a P/LP variant, 94% and 100% had a family history of CVD, respectively. By comparison in those without a P/LP variant, 59% and 73% had a family history of CVD. Out of 124 patients, only 13 had genetic testing through their clinical care, all of which occurred post-transplantation. 5/13 of these patients had a P/LP variant. Conclusions: This retrospective study showed a significant yield of genetic testing in HT patients. Notably, the overall prevalence of P/LP variants was nearly identical between NICM and ICM patients, with a higher rate of CM-related variants in the NICM group. We suggest that a genotype-first approach of screening all HT patients for genetic mutations enables earlier identification of actionable variants in HT probands and their family members than the current phenotype-guided approach.

Abstract 16815: Outcomes of Cardiac Sympathetic Denervation via Cautery Ablation for Ventricular Arrhythmia: A Single Center Study

Introduction: Cardiac sympathectomy denervation (CSD) has been demonstrated to reduce ventricular arrhythmia (VA) burden and to improve arrhythmia-free survival. Early evidence for the clinical antiarrhythmic benefits for CSD was established in patients with long-QT syndrome and catecholaminergic polymorphic VT (CPVT). Its benefit has subsequently been shown to extend to other undifferentiated cardiomyopathies. Hypothesis: Literature on CSD for VA has been limited due to a small number of patients. Our retrospective study is to review patients who underwent CSD for VA at our center via cautery ablation. Methods: We identified 9 patients who underwent CSD from 4/2018 to 2/2022. Electronic medical record was reviewed for clinical history and outcomes. Results: Mean age was 52±17 and 5 patients (55.6%) were male. Seven patients (77.8%) had nonischemic cardiomyopathy (NICM) and 2 patients (22.2%) had CPVT. Mean LVEF was 43±19% and 5 patients (55.6%) had heart failure with NYHA class 3±0.7. Five patients (55.6%) underwent CSD in outpatient setting and 4 patients (44.4%) had polymorphic VT. Six patients (66.7%) had prior catheter-based VT ablation, 1 patient (11.1%) had prior ganglion block, and 4 patients (44.4%) had history of VT storm. All patients were on antiarrhythmics ranging from a beta blocker monotherapy to a combination of class Ic, class III, and a beta blocker. Seven patients (77.8%) had a defibrillator prior to CSD. All patients underwent CSD (7 with bilateral and 2 with left only) without any procedural complication. Five patients (55.6%) had recurrence of VA in 423±567 days with follow-up duration of 729±478 days. Three patients (33.3%) underwent heart transplant or LVAD and three patients (33.3%) died in 426±396 days since CSD. Overall, 3 patients (33.3%) including 2 CPVT patients and one NICM patient with normal EF were free of death, sustained VT, or advanced heart failure therapies. Conclusions: CSD via cautery ablation is safe and effective for patients with refractory VA to antiarrhythmics and/or VT ablation. Success rate appeared to be higher in patients with CPVT and normal EF. Lower rate of survival and freedom from VT or transplant/LVAD compared to published literature may reflect our sick population.

Abstract 17084: Impact of Hereditary Gene Mutations on Outcomes in an Ethnically Diverse Patient Cohort With Nonischemic Dilated Cardiomyopathy

Introduction: Nonischemic cardiomyopathy (NICM) is a leading cause of heart failure (HF). Heritable gene mutations are found in a subset of these cases and help to identify at risk individuals. The purpose of this study is to characterize the impact of genotype on clinical outcomes. Methods: Data from a single center registry of patients who underwent cardiomyopathy and arrhythmias gene panel testing between 2018 and 2022 was used. Patients with an LVEF &lt; 50% without a history of hypertrophic, infiltrative or ischemic cardiomyopathy were included. Genotyping, demographics, and clinical data including HF and major ventricular arrhythmia (MVA) outcomes were collected. Patients were stratified by genotype ((+): Pathogenic/Likely Pathogenic; (-): VUS/Likely Benign/Benign/no variant). Genotype (+) patients were also grouped by functional gene class. Chi Square and Wilcoxon testing were used for between group comparisons. Kaplan Meier with log-rank testing was used for time to event analyses. Results: This study included 350 patients with a median age of 54 years (IQR: 42-65 years) at last follow up. Table 1 shows demographics and outcomes. Genotype (+) patients had more HF and MVA events. There was a trend towards genotype predicting HF and MVA at all ages, with curves separating after age 26 (p = 0.0475) Figure 1. Genotype (+) LMNA patients had HF and MVA events at earlier ages compared to Genotype (-) (n=6, 85.7 %, p = 0.005). Conclusion: NICM patients with a hereditary gene identified have worse outcomes than those without, suggesting an opportunity to improve risk stratification and guide patient management decisions with genetic testing.