Primary Prevention Implantable Cardioverter-defibrillator Research Articles

Long-term follow-up in patients with hypertrophic cardiomyopathy after defibrillator implantation: analysis of appropriate and inappropriate therapy

Abstract Background Treatment with implantable cardioverter-defibrillators (ICD) is effective for prevention of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). Assessment of SCD risk and identification of patients most likely to benefit from primary prevention ICD is challenging. Purpose To investigate the long-term incidence of appropriate and inappropriate ICD therapy in patients with HCM. Methods This was a retrospective cohort study including all patients with HCM and ICDs implanted between 1995 to 2022 in our region (population 2.6 million). Both patients treated with primary and secondary prevention ICD were included. Data was retrieved from medical records. Patients with an ICD implanted for primary prevention were stratified into risk groups according to European Society of Cardiology HCM Risk-SCD score. Results We included 187 patients (65% male) with HCM and ICDs implanted for primary (80%) or secondary (20%) prevention. The median age at ICD implantation was 50 years (IQR: 40 to 61 years). During a mean follow-up of 9 years (IQR: 4 to 12 years), 53 patients (28%) experienced appropriate ICD therapy (antitachycardia pacing and/or shock), while 17 (9%) patients received inappropriate therapy. Patients with an ICD as secondary prevention were almost twice as likely to receive appropriate ICD therapy compared to patients with a primary prevention ICD (42% vs. 25%, p=0.04). The proportion of patients receiving appropriate shocks was 7 times higher in patients with an HCM Risk-SCD score ≥6% compared to patients with a risk score <4% (29% vs. 4%, p<0.001). There was no significant difference in the proportion of appropriate shocks between patients with a HCM Risk-SCD score ≥6% and patients with a risk score of 4%-6% (29% vs. 21%, p=0.49). (Figure 1). Conclusion One in four patients with HCM treated with an ICD experienced appropriate device intervention during 9 years of follow up. Patients with an HCM Risk-SCD score ≥6% had a 7-fold higher risk of appropriate ICD therapy compared to patients with an HCM Risk-SCD score <4%. There was no significant difference in the risk of appropriate shock therapy between patients with a risk score ≥6% and patients with a risk score of 4%-6%. The findings indicate the need for improved selection of patient with HCM for implantation of ICD’s.

The challenge of risk stratification in hypertrophic cardiomyopathy: clinical, genetic and imaging insights from a quaternary referral centre

Abstract Background Hypertrophic cardiomyopathy (HCM) is the commonest genetic cardiomyopathy and may result in sudden cardiac death (SCD). Clinical risk stratification scores are utilised to estimate SCD risk and determine potential utility of a primary prevention implantable cardioverter defibrillator (ICD). Methods Patients with a confirmed diagnosis of HCM from a quaternary HCM service were defined according to clinical characteristics, genetic profiles and cardiac imaging results. European Risk-SCD score and American Heart Association / American College of Cardiology (AHA/ACC) Score were calculated. The primary outcome was cardiac arrest. Results 380 patients with HCM were followed up for a median of 6.4 years. 18 patients (4.7%) experienced cardiac arrest, with predictive factors being younger age (37.2 vs 54.4 years, p=0.0041), unexplained syncope (33.3% vs 9.4%, p=0.007), non-sustained ventricular tachycardia (50.0% vs 12.7%, p<0.0001), increased septal thickness (21.5 vs 17.5mm, p=0.0003), and presence of a sarcomeric gene mutation (100.0% vs 65.8%, p=0.038). The Risk-SCD and AHA/ACC scores had poor agreement (kappa coefficient 0.38). Risk-SCD score had poor sensitivity (44.4%), classifying 55.6% of patients with cardiac arrest as low-risk but was highly specific (93.7%). AHA/ACC risk score did not discriminate between groups significantly. 20 patients (5.3%) died, with most >60-year-olds having a non-cardiac cause of death (p=0.0223). Conclusion This study highlights limited (38%) agreement between the Risk-SCD and AHA/ACC scores. Most cardiac arrests occurred in ostensibly low or medium-risk patients under both scores. Appropriate ICD selection remains challenging. Utilising newer markers such as cardiac MRI and genetic findings may assist future risk refinement.

Temporal trends in baseline characteristics of implantable cardioverter defibrillator recipients for primary prevention of sudden cardiac death- The DAIPP program

Abstract Introduction Since expanding the indication for implantable cardioverter defibrillators (ICD) to primary prevention, the patient population of ICD carriers continues to evolve over time. In pursuit of progressively decreasing the burden of sudden cardiac death, improved patient selection and risk-benefit assessment demand, among others, awareness of these temporal changes in clinical baseline characteristics of the ICD population. Purpose The aim was to explore the temporal differences in baseline characteristics of ICD recipients implanted for primary prevention of sudden cardiac death (SCD), and perioperative complications, to improve understanding of ICD population selection over the last two decades in a real-world setting. Methods The Primary Prevention ICD French Registry (DAI-PP program) was initiated in 2002 with an overall aim to assess the risk-benefit ratio of the introduction of ICD for primary prevention over a 20-year period, including a pilot evaluation that finished in 2012. The pilot study laid ground for the ongoing prospective DAIPP Consortium that started in 2018 and is aiming to follow 10000 patients under remote monitoring, using a specific integrational research platform. The two cohorts are in this study compared with regards to baseline characteristics as well as perioperative outcomes, i.e., early mortality and procedural complications. Results This study included 8432 participants, 5521 from the pilot study and 2211 from the prospective trial, with a median follow up of 2.36 (IQR 1.25-3.75) years. Median age was 64 (IQR 56-71) years, 17% female and 61% had ischemic heart disease. Baseline characteristics that remained stable over time were age, cancer burden. Compared to the 2002-2012 period, recent findings found a significant increase in the proportion of females (15 vs 20%, p <0.001), pauci-symptomatic patients (New York Heart Association Functional class-NYHA II, 41 vs. 57%, p <0.001), narrow QRS patients (31 vs. 43%, p<0.001), use of subcutaneous ICD (0 vs. 14%, P<0.001) and more comorbidities including an increase in diabetes, and slight increase in stroke. Regarding pharmacological treatment, there was an increase in use of 2 or 3 medications (2: 6.5% to 16% p<0.001; 3: 20% to 33%, p<0.001) where more received beta blockers and amiodarone in the contemporary study. Perioperative complications decreased over time (13% to 7.9% p<0.001) with a decrease in early reinterventions (1.3% to 0.1% p<0.001) and discrete fall in number of infections (0.7% to 0.1%, p<0.001) and pocket hematoma (4.4% to 3.0% p<0.001). A slight upward trend in number of lead dislodgements was seen over time (1.3% to 1.7% p<0.001). See Table 1 for perioperative complications. Conclusion The primary prevention ICD population has significantly changed over time. An increase in women, comorbidities, and use of 2-3 medications was seen, coupled with more participants receiving a subcutaneous ICD. Perioperative complications decreased over time.

N-terminal pro-B-type natriuretic peptide for prediction of ventricular arrhythmias: data from the SMASH Study

Abstract Background Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations predict heart failure (HF) and mortality, but whether NT-proBNP predicts ventricular arrhythmias (VA) is not clear. Purpose We hypothesize that high NT-proBNP concentrations associate with the risk of incident VA, defined as adjudicated ventricular fibrillation or sustained ventricular tachycardia. Methods In a prospective, observational study of patients treated with implantable cardioverter defibrillator (ICD), we analyzed NT-proBNP concentrations at baseline and after mean 1.4 years in association to incident VA. Results We included 491 patients (age 66±12 years, 83% men) out of whom 51% had a primary prevention ICD indication. The median NT-proBNP concentration was 567 (25-75 percentile 203-1480) ng/L, and patients with higher concentrations were older with more HF and ICD for primary prevention. During mean 3.1±0.7 years, 136 patients (28%) had ≥1 VA. Baseline NT-proBNP concentrations were associated with risk of incident VA (HR 1.39 [95%CI 1.22-1.58], p<0.001) (Figure1), HF hospitalizations (HR 3.38 [95%CI 2.69-4.25], p<0.001) and all-cause mortality (HR 2.49 [2.05-3.04], p<0.001) (Figure2), which persisted after adjusting for age, sex, BMI, CAD, HF, renal function, and LVEF. The association with VA was stronger in secondary vs primary prevention ICD indication: HR 1.59 (95% CI 1.34-1.88 C-statistics 0.71) vs HR 1.25 (1.02-1.52, C-statistics 0.55), p-for-interaction=0.06. Changes in NT-proBNP during the first 1.4 years did not associate with subsequent VA. Conclusions NT-proBNP concentrations are associated with the risk of incident VA after adjustment for established risk factors, with the strongest association in patients with a secondary prevention ICD indication.

Mortality benefit of implantable cardioverter-defibrillators for primary prevention of sudden cardiac death: a real-world analysis

Abstract Background Nearly 1,000 people suffer an out-of-hospital sudden cardiac arrest daily in the United States, with only 10% surviving when treated by emergency medical services. Implantable cardioverter-defibrillators (ICDs) are a proven first-line treatment in limiting sudden cardiac death, but the evidence has become dated. We sought to assess the survival benefit of ICDs in a contemporary population. Purpose Using a real-world database, we aimed to determine the current impact of ICDs on mortality in primary prevention patients. Methods Data were obtained from a de-identified electronic health record database. We included patients that met ICD primary prevention indication (PPI) implantation criteria between 2012 and 2019, had one year of available data before the PPI, and survived for at least one year post-PPI. Patients were split into 2 groups based on ICD implant status (implanted vs not implanted) within one year after PPI. The primary endpoint was the overall mortality rate, beginning at one-year post-PPI. Propensity matching was performed to account for baseline differences between patients that did and did not receive an ICD, and all-cause mortality rates were compared using the Kaplan-Meier method and Cox proportional hazard model. Results A total of 25,296 patients were identified as having a PPI for ICD implantation, of which 2,118 (8.4%) were implanted with an ICD within a year. Implanted patients were younger than non-implanted patients (63.4 vs 66.1 years) and had a smaller proportion of females (25.0% vs 36.7%). After 4 to 1 propensity matching, patients who did not have an ICD implanted had a mean age of 63.6 years and were 25.1% female. In the matched cohort, the 5-year all-cause mortality rate was 37.6% (CI: 33.2%-41.7%) in PPI patients who received an ICD and 44.9% (CI: 42.8%-47.0%) in those that did not receive an ICD. A Cox proportional hazard model revealed a 25.3% lower risk of all-cause mortality in PPI patients implanted with an ICD compared to PPI patients without an ICD (HR: 0.747; CI: 0.670-0.834; p<0.001 [Figure 1]). Conclusion In a large cohort of PPI patients that survived at least one year after indication, those implanted with an ICD during that year had a 25.3% lower risk of all-cause mortality than similar patients who did not receive an ICD, consistent with landmark trials. Thus, ICD implantation continues to be associated with a reduction in all-cause mortality in PPI patients at risk for sudden cardiac death.

Neurohormonal status is associated with long-term appropriate implantable cardioverter defibrillator therapy for life-threatening ventricular arrhythmia

Abstract Background Neurohormonal status is associated with the risk of life-threatening ventricular arrhythmia. Purpose We aimed to assess whether neurohormonal status in patients with an implantable cardioverter defibrillator (ICD) is correlated with the risk of long-term appropriate shock or overdrive delivered by the ICD for life-threatening arrhythmia. Methods A total of 331 clinically stable patients with ICD without any past history of shock or overdrive for life-threatening ventricular arrhythmia were enrolled in a two-center prospective cohort and followed up for a median time of 7.9 years. At enrolment, patients’ medical history, treatment, clinical and imaging data were recorded and, blood and, blood samples were drawn for the assessment of standard biological parameters as well as 3 neurohormones (aldosterone, A type NT-pro-Atrial natriuretic peptide (ANP) and MR-pro-Adrenomedullin (ADM). The primary endpoint of the study was the occurrence of appropriate shock or overdrive delivered by the ICD (ICD therapy). A multivariable cox model adjusted on age, gender, primary or secondary prevention ICD as well as all baseline variables unequally distributed between groups with or without ICD therapy was used for the assessment of the relationship between the 3 neurohormones and the primary endpoint. Results The population consisted of patients with a mean age of 60±15 years, among which 59(18%) women and 160(48%) with a secondary prevention indication for ICD. At baseline all data were similar between patients with or without ICD therapy with the exception of weight, systolic blood pressure, left ventricular ejection fraction (LVEF) and serum potassium and creatinine levels. No other variable, including MADIT and SHOCKED score were significantly associated with the risk of ICD therapy. Death was recorded in 114(34%) patients and a total of 78(24%), 76(23%) and 106(33%) patients had appropriate shock, overdrive and ICD therapy respectively during the follow-up. On multivariable analysis, highest levels of ANP and lowest levels of ADM but not aldosterone were independently associated with life-threatening ventricular arrhythmia requiring ICD therapy (table). Other correlates of ICD therapy were lower LVEF and, higher weight, serum potassium and creatinine concentrations. ANP and ADM had a stepwise additive impact on the risk of ICD therapy. (Figure 1) Conclusions In a stable all comer population with ICD and no history of ICD therapy, blood levels of neurohormones ANP and ADM are associated with the risk of life-threatening ventricular arrhythmia requiring ICD-delivered shock or overdrive independent of other correlates. ANP and ADM concentrations may be useful in identifying patients at high risk of such arrhythmia and who may most benefit from ICD implantation.

Impact of neuromuscular assessment on arrhythmic risk in LMNA cardiomyopathy

Abstract Background The current Risk Score for Life-Threatening Ventricular Tachyarrhythmias (LTVT) in LMNA cardiomyopathy does not consider the frequent association between cardiac and neuromuscular phenotypes as a part of a multisystemic disease. In particular, the prognostic value of tendon retractions (TR) has been recently described. Objectives We aimed to assess the prognostic role of TR in a cohort of probands with LMNA cardiomyopathy undergoing multidisciplinary workup at a referral center. Methods We included 28 probands with LMNA cardiomyopathy undergoing regular, prospective follow-up at a national referral center for laminopathies. All patients underwent extensive baseline characterization, including complete neuromuscular examination and systematic assessment of TR. Indications to implantable cardioverter defibrillators (ICD) for the primary prevention of sudden cardiac death were guideline-based. Patients were clustered in tertiles according to their baseline LMNA-Risk Score. The primary endpoint was the 5-year occurrence of LTVT, namely arrhythmic cardiac death, VF, sustained VT, or appropriate ICD shocks. Results Of the 28 probands with LMNA cardiomyopathy (mean age 33±15 years, 50% males, mean LVEF 55±14 %), neurological assessment identified 14 patients (50%) with TR, including 8 cases with no other signs of neuromuscular involvement. At baseline assessment, the median LMNA-Risk Score was 10% (IQR 6-20%). By 5-year follow-up, 9 patients (32%) met the primary endpoint, including three patients in the lowest tertiles of risk (median LMNA-Risk Score 23, range 6-15%). While other variables showed no remarkable differences between groups, the prevalence of TR was 78% among cases experiencing LTVT and 37% otherwise. The presence of either baseline LMNA-Risk score at the highest tertile (>17%) or TR was 100% predictive of 5-year LTVT (9/9 vs. 7/19, p=0.003). Results did not change after reassessment by the end of follow-up (15±5 years). Conclusions Our preliminary data suggest that the inclusion of TR in risk stratification may result in a better patient selection for primary prevention ICD implant in LMNA cardiomyopathy.

Efficacy of implantable cardioverter-defibrillator in non-ischemic systolic heart failure in patients with and without chronic kidney disease: an extended follow-up analysis of the DANISH trial

Abstract Background Patients with heart failure (HF) and chronic kidney disease (CKD) may have an increased risk of death from causes competing with arrhythmic death, which could have implications for the efficacy of implantable cardioverter defibrillators (ICDs). Purpose In this extended follow-up study of the Danish Study to Assess the Efficacy of primary prevention of Implantable Cardioverter Defibrillators in Patients with Non-ischemic Systolic Heart failure on Mortality (DANISH), adding four years of additional follow-up, we examined the long-term effects of primary-prevention ICD implantation, compared with usual medical care, according to baseline CKD status. Methods In the DANISH trial, 1,116 patients with non-ischemic systolic HF were randomized to receive an ICD (N=556) or usual care (N=550). Outcomes were analyzed according to CKD status (eGFR ≥/< 60 mL/min/1.73 m2) at baseline. The primary outcome was death from any cause. Secondary outcomes were cardiovascular death and sudden cardiovascular death. Results In total, 1,113 patients had an available eGFR measurement at baseline (median eGFR 73 ml/min/1.73 m2), and 316 (28%) had CKD. During a median follow-up of 9.5 years, ICD implantation, compared with usual medical care, did not reduce the rate of death from any cause (no CKD, HR 0.81 [95% CI, 0.64-1.03]; CKD, HR 0.92 [0.68-1.26]; P for interaction=0.31) or cardiovascular death (no CKD, HR 0.76 [0.57-1.02]; CKD, HR 0.95 [0.66-1.36]; P for interaction=0.21), irrespective of baseline CKD status. Similarly, baseline CKD status did not modify the beneficial effects of ICD implantation on sudden cardiovascular death (no CKD, HR 0.57 [0.32-1.00]; CKD, HR 0.60 [0.31-1.14]; P for interaction=0.70). Conclusions Primary-prevention ICD implantation did not provide an overall survival benefit regardless of baseline kidney function in patients with non-ischemic systolic heart failure.Figure

Long-term outcomes in carriers of the familial idiopathic ventricular fibrillation linked to the DPP6 locus

Abstract Background Idiopathic ventricular fibrillation (IVF) is a malignant condition with no clinical sequelae except for ventricular fibrillation. The genetic basis is ill-defined but in 2009 a Dutch founder variant - the DPP6 risk haplotype - was linked to a familial form of IVF characterized by a very high incidence of sudden cardiac arrest (SCA) and sudden cardiac death (SCD). Consequently, for more than a decade asymptomatic haplotype-carriers from the ages of 18 (male) and 25 (female) have had an implantable cardioverter-defibrillator (ICD) inserted. However, the associated long-term outcomes in these individuals is unknown. Purpose To assess the long-term outcomes of DPP6 risk haplotype-carriers who presented to our tertiary referral center and qualified for ICD insertion. Methods Clinical follow-up information of DPP6 risk haplotype-carriers, including the occurrence of SCD, SCA, appropriate ICD shocks, and ICD-related complications, was collected through February 2023. ICD-carriers were classified as either asymptomatic (primary prevention), or with previous sudden cardiac arrest (secondary prevention). Survival rates are presented using a survival curve and were compared with the log-rank test. Results A total of 118 haplotype-carriers (62 males) were included. One-hundred nine (92%) carriers had an ICD inserted, for primary (n=85) or secondary prevention (n=24), and 9 patients refused a primary prevention ICD. Among primary prevention ICD-carriers and those who refused implantation (n=94), 9 (10%) patients experienced a total of 28 appropriate shocks, there was 1 SCA and no deaths, during a median follow-up of 11 years (IQR 7-13; Figure). Of these, 9 patients were ever treated with quinidine and 5 still used quinidine at last follow-up. Among secondary prevention ICD carriers, 20 (83%) patients experienced a total of 225 appropriate shocks and one patient died, during a median follow-up of 13 years (IQR 10-16). Of these patients, 11 were ever treated with quinidine, of whom one patient discontinued quinidine due to adverse effects. Overall, 14 (13%) patients experienced inappropriate shocks and 16 (15%) experienced other ICD-related complications. Conclusion Predictive genetic testing of the DPP6 haplotype provides the unique opportunity to identify asymptomatic family members at risk for SCD and insert prophylactic ICDs just on the basis of carrying the risk haplotype. Approximately 10% of DPP6 haplotype-carriers who qualified for ICD insertion for primary prevention, predominantly males, experienced appropriate ICD shocks or SCA during 11 years of follow-up, indicating that our approach to ICD implantation has presumably saved several lives. In those with an ICD for secondary prevention the incidence of appropriate ICD shocks was high, often despite quinidine therapy.Survival until appropriate shock or SCA

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<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 15930: Using Charlson Comorbidity Index to Predict 1-Year All-Cause Mortality in ICD Recipients

Introduction: Primary prevention implantable cardioverter-defibrillators (PP-ICD) are indicated in patients with left ventricular ejection fraction (LVEF) ≤ 35% despite 3 months of maximally tolerated guideline directed medical therapy (GDMT), who are expected to survive at least 1 year. The Seattle Heart Failure Score, commonly used for evaluation of 1 year survival, only addresses heart failure mortality. The Charlson Comorbidity Index (CCI) is a validated model of comorbid conditions used to predict 1-year all-cause mortality. Objectives: We aimed to create a predictive model using the CCI to guide eligibility for PP-ICD based on predicted 1-year all-cause mortality in patients with severe cardiomyopathy. Methods: We analyzed clinical data from the University of Pittsburgh Medical Center, a large multi-hospital system, between January 2010 and July 2021. Patients receiving PP-ICD were included. We used a logistical regression model based on patients’ CCI, age, race, mean number of GDMT medications, the presence of coronary artery disease (CAD), and baseline LVEF. Results: Of the total cohort of 2,864 patients (mean age 67±12 years; Male 69%; White 85%; LVEF 24±7%; CAD 62%), 235 (8.2%) patients died within 1 year. Patients were on average prescribed 2.0±0.8 GDMT agents and had a mean CCI of 1.4± 1.6. CCI was significantly associated with adjusted 1-year mortality (OR 1.41 per standard deviation of CCI, 95% CI 1.35-1.71, p< 0.001). A receiver operator curve was generated (Figure 1) and a CCI cutoff of 1.54, yielded a sensitivity of 71% and a specificity of 59% (AUC 0.70). Conclusions: Our data demonstrate that a model incorporating the CCI can predict 1-year all-cause mortality in PP-ICD recipients with modest accuracy and could therefore assist in shared-decision making around PP-ICD therapy. Future work should focus on refining the model for higher predictive accuracy.

Abstract 16061: Correlation Between Obesity and Ventricular Tachycardia in Individuals With HFrEF: Analysis From the DERIVATE Cohort

Background: Ventricular arrhythmias (VA) are a significant cause of morbidity and mortality in heart failure. Obesity has been proposed as a potential risk factor for increased VA incidence, but previous studies with limited sample sizes and single-center enrollment have yielded conflicting results. To address this, we utilized data from the international multicenter DERIVATE study, which includes individuals with heart failure with reduced ejection fraction (HFrEF) as well as baseline cardiac MRI (CMR) assessment of myocardial structure and function. We sought to investigate the association between obesity and sustained ventricular tachycardia (VT) occurrence in this patient population. Methods: Study cohort comprised of patients enrolled in the CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DefibrillAtor ThErapy (DERIVATE) registry who had HFrEF and had simultaneous baseline CMR and echocardiography evaluation. Demographics, comorbidities, and CMR variables were used to evaluate the correlation between obesity and ventricular tachycardia. Obesity was defined as BMI>30 kg/m 2 . A multivariate logistic regression analysis was used to determine the association between clinical, imaging variables and the occurrence of VA. Statistical software SAS 9.4 was used to perform the analysis. Results: Among 2,537 individuals, 505 (19.9%) were obese. Mean age was 60 years and 23.9% were female. Median follow-up was 994 days. Obesity was not associated with VT (OR 0.94, CI 0.60-1.48, P=0.79). The occurrence of VT was associated with the presence of an ischemic cardiomyopathy (OR 1.76, CI 1.37-2.26, p<0.01), and amiodarone use (OR 1.89, CI 1.28-2.80, P<0.01). As expected, left ventricular ejection fraction was inversely associated with VT (OR 0.96, CI 0.94-0.98, P<0.01), while indexed left ventricular end diastolic volume was directly associated with VT (OR 1.01, CI 1.00-1.01, P<0.01). Conclusions: In individuals with HFrEF, there was no association between obesity and the occurrence of sustained VT. The presence of ischemic cardiomyopathy was associated with higher incidence of sustained VT, as well as larger indexed left ventricular end diastolic volume which is an imaging marker of HF chronicity and severity.

Abstract 14398: Predictors of Major Adverse Cardiac Events in Individuals With Left Bundle Branch Block and Cardiac Resynchronization Therapy: Analysis From the Derivate Registry

Background: Cardiac resynchronization therapy (CRT) plays an important role in managing patients with advanced heart failure (HF) with reduced ejection fraction and interventricular conduction block, as it reestablishes synchrony and cardiac function while reducing the risks of HF-related hospitalizations and mortality. Despite the well-described advantages of CRT, approximately 30% to 40% of patients fail to respond to therapy. Therefore, our study aimed to define patient characteristics associated with major adverse cardiac events (MACE) in individuals with left bundle branch block (LBBB) who received CRT. Methods: The study cohort included patients enrolled in the CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DefibrillAtor ThErapy (DERIVATE) registry who had LBBB and had previously undergone CRT. We defined MACE as a composite outcome including cardiac death, hospitalization for heart failure, or major adverse arhythmic events. Cox regression analysis was used to examine the relationship between MACE and CRT therapy. Kaplan-Meier curves were utilized to explore the association between CRT and cardiac death. Results: Out of 300 individuals, 144 (48%) experienced MACE. The cohort had a mean age of 63.9 ± 10.9, with 29% being male. The median follow-up period was 1285 days. Ischemic cardiomyopathy was identified as an independent predictor of MACE (HR = 3.54; 95% CI [2.31-5.41]; P<0.01) and cardiac death (HR = 24.10; 95% CI [10.71-54.21]; P<0.01) in patients with LBBB and CRT. Amiodarone therapy was associated with a 1.91-fold (95% CI [1.20-3.05]; P=0.01) increased risk of MACE. Notably, multivariate analysis did not reveal a significant association between gender, hypertension, renal function, diabetes mellitus, or NYHA class III/IV and the occurrence of MACE. Conclusion: Our findings suggest that ischemic cardiomyopathy and the use of amiodarone therapy are independent predictors of MACE in patients with LBBB who previously underwent CRT. These findings suggest that patient-level characteristics are important predictors of MACE; however, further research is needed to better understand the interplay between ejection fraction, conduction disease, and patient characteristics post-CRT therapy.

Abstract 15327: Clinical Outcomes of Methamphetamine-Associated Cardiomyopathy Compared to Ischemic Cardiomyopathy: A Single Institution Retrospective Longitudinal Study

Background: Methamphetamine-associated cardiomyopathy (MAC) leads to significant morbidity and mortality. The benefit of implantable cardioverter-defibrillator (ICD) in this population is poorly characterized. Aims: To evaluate ICD use and outcomes in patients with MAC compared to ischemic cardiomyopathy (ICM). Methods: Electronic health record (EHR) was queried for all heart failure hospitalizations using ICD-9 codes between 2011 and 2019. Patients with an EF ≤ 35% were included. The MAC cohort was derived from this population and defined by ICD-9 code or positive urine toxicology and compared to ICM cohort. Baseline characteristics and outcomes were extracted from the EHR. MACE was defined as death, ventricular tachycardia, cardiac arrest, rehospitalization, atrial fibrillation (AF) or stroke. Results: The study included 294 patients in the MAC group and 373 patients in the ICM group. MAC patients were younger (56 vs 61 years, p<0.001) compared to ICM (table 1). Readmission rates for heart failure at one year were similar (13% vs 11.2%, p=ns). Significantly fewer patients with MAC had ICD for primary prevention (15.0% vs 27.9%, p<0.001). Mortality and AF were lower in MAC compared to ICM, however VT (2.38% vs 5.09%, p=0.072) and cardiac arrest (6.1% vs 7.8%, p=0.408) were similar between the two groups. MACE outcomes were worse in the ICM cohort (38.3% vs 21.1%, p=0.012) than MAC. In the MAC cohort, ICD presence was associated with 56.82% incidence of MACE compared to 40.00% without ICD (OR = 1.97, CI 1.032-3.77, p = 0.040) mainly due to higher AF hospitalization (22% vs 8%, p=0.01). Conclusion: ICM patients had higher mortality and atrial fibrillation compared to MAC. ICD implantation for primary prevention was not associated with reduced mortality, however this cohort had higher AF hospitalization. We need further studies to assess the benefit of ICD in MAC.

Abstract 13746: Mental Health and Implantable Cardioverter Defibrillator Implantation in Black Patients at Risk for Sudden Cardiac Death

Introduction: Black patients with guideline indications for implantable cardioverter defibrillators (ICD) have lower rates of implantation compared to White patients. The Educational Videos to Address Racial Disparities in ICD Therapy Via Innovative Designs (VIVID) trial enrolled self-identified Black individuals with chronic systolic heart failure and studied the impact of a video-based decision-support tool on decisional quality and ICD implantation. Hypothesis: We hypothesized that depressive symptoms are associated with greater decisional conflict and lower rates of ICD implantation among study participants. Methods: Participants were administered the Patient Health Questionnaire-2 (PHQ-2) depression screen; and the 12-Item Short-Form Health Survey, from which we derived the Mental Component Summary-12 (MCS-12). A decisional conflict scale (DCS) adapted from the Ottawa framework for shared decision-making was used to assess decisional conflict associated with the decision for ICD implantation. An analysis of covariance was used to assess differences in DCS scores. Multivariable logistic regression was used to examine the association between mental health scores and ICD implantation at 90 days. Results: Among 306 included participants, 60 (19.6%) reported depressed mood and 142 (46.4%) reported anhedonia. Participants with the lowest MCS-12 scores (poorer mental health) had greater decisional conflict regarding ICD assent compared to those with the highest MCS-12 scores (adjusted mean difference in DCS score = 3.05 [95% CI: 0.32, 5.78]). By 90-day follow-up, 204 participants (66.6%) underwent ICD implantation. There was no significant association between either PHQ-2 score or MCS-12 score and ICD implantation. Conclusions: Depressed mood and anhedonia were prevalent among Black patients considering primary prevention ICD. Poorer mental health did not impact the likelihood of ICD implantation in this population.

Abstract 11836: A Rare Cause of Recurrent Myocardial Infarction: Genetic Testing Cracks the Case

A 29-year-old man presented to our institution with acute, severe substernal chest pain. An ECG on arrival revealed 3mm ST-elevations in the lateral leads with reciprocal depressions in the inferior leads. Troponin-I was above assay (>50 ng/mL). Emergent coronary angiography showed normal coronary arteries, and left ventriculogram showed no wall motion abnormalities. A transthoracic echocardiogram showed normal biventricular size, wall thickness, and ejection fraction (EF). This was his fifth episode of chest pain over the past 10 years, consistent with prior presentations of ST-elevation myocardial infarction and angiographically normal coronary arteries. A prior cardiac magnetic resonance imaging (MRI, 6 years before the current presentation) revealed increased T2 signal intensity and subepicardial late gadolinium enhancement (LGE) in the septum, inferior, and inferolateral walls, suggestive of nonischemic acute myocardial injury. A repeat cardiac MRI during the current presentation showed mildly reduced biventricular systolic function (LVEF 52%, RVEF 36%), and again showed increased T2 signal intensity and subepicardial LGE involving the septum, inferior and inferolateral walls. The anterior and anterolateral walls were also now involved. Endomyocardial biopsy (EMB) showed focal interstitial fibrosis with no evidence of active myocarditis. On telemetry he was noted to have runs of non-sustained ventricular tachycardia (NSVT). Serologic evaluation was negative for parvovirus, cytomegalovirus, and Chagas disease. Erythrocyte sedimentation rate and C-reactive protein levels were normal. Genetic testing was performed at our newly established cardiovascular genetics program, which showed a pathogenic truncating mutation in the desmoplakin gene (DSP). DSP cardiomyopathy (CM) is an LV-predominant arrhythmogenic CM, which can present with episodic myocardial injury, and has a high disposition for ventricular arrhythmias with subepicardial LGE pattern often proceeding LV systolic dysfunction. A primary prevention implantable cardioverter-defibrillator was placed given extent of LGE and NSVT burden in the context of DSP variant. This case illustrates the importance of genetic testing in identifying rare CM phenotypes.

Abstract 15634: Primary Prevention Defibrillator Use in a Safety-Net Setting

Introduction: Disparities in use of implantable cardioverter-defibrillators (ICD) for primary prevention have been documented; however, whether ICDs may be underutilized within a safety-net healthcare system has not been studied. Methods: Using an electronic health record cohort of all patients with heart failure (HF) who received care within the public safety-net system in San Francisco from 2001-2018 linked to device implantation records from two health systems, we identified all patients with ICD implantation (adjudicated with manual chart review) and primary prevention ICD-eligible with no indication for secondary prevention ICD, EF<35% on 2 echocardiograms at least 90 days apart, HF hospitalization (to increase specificity for symptomatic HF), and prescribed beta blocker and ACEi/ARB. For exploratory survival analysis, eligibility and follow up started at the second echocardiogram. Results: Out of 14,230 patients with HF, at least 384 patients were potentially eligible for primary prevention ICD, but only 9 (2.3%) had an ICD implanted (2 CRT-D, 7 ICD). Of these 6 were nonischemic, and 3 had revascularized ischemic cardiomyopathy. Those who received ICD were younger (47 years vs 55 years; p=0.05), with lower rates of substance use (Table). Among 4 patients who died after ICD, median survival after device placement was 2.8 years (range 0.73 to 7.3); among 5 still alive, median follow up is 6.2 years (range 5.5 to 7.0). In an exploratory analysis, survival did not greatly differ by ICD placement (logrank p=0.53; age-adjusted HR 1.55; 95%CI 0.57-4.24). Conclusion: Among individuals receiving care at a safety-net system in San Francisco, even acknowledging that not all barriers to ICD placement are measured, very few guideline-eligible patients received primary prevention ICD. Additional studies are needed to identify patient-level and systems-level barriers to referral and implantation specific to a diverse, publicly insured patient population.

Abstract 15246: Myocardial Deformation for Prediction of Major Arrhythmic Events in Patients With Non-Ischemic Cardiomyopathy and Primary Prevention Implantable Cardioverter Defibrillators

Introduction: Sudden cardiac death is a major cause of mortality in patients with non-ischemic cardiomyopathy (NICM). Implantable cardioverter-defibrillator (ICD) is an established prophylactic measure. But, optimal identification of patients with greatest likelihood of benefiting poses ongoing challenges. Objective: To assess the prognostic value of myocardial deformation for predicting ICD intervention while accounting for competing mortality risk. Methods: 180 NICM patients eligible for primary prevention ICD underwent cardiac magnetic resonance (CMR). Myocardial strains (left ventricular radial, circumferential, longitudinal; left atrial; and right ventricular free wall longitudinal strain (RV GLS)) were measured via CVI42 feature tracking. In a multivariable Fine-Gray competing risk model, incremental values of strains were assessed, adding to a baseline model based on clinical features and late gadolinium enhancement (LGE). The primary endpoint was ventricular tachycardia/fibrillation treated with ICD intervention, including shocks or anti-tachycardia pacing. Results: 159 patients with ICD (117 male; 54 ± 13 years) were included for final analysis (follow-up: 1176±960 days; median: 896). 26 patients met the primary endpoint. RV GLS showed a statistically significant difference between patients with and without events (-12.5% ± 5 vs -16.4% ± 5.5, p = 0.001). Univariate analyses revealed that LGE and RV GLS were significantly associated with outcome, even after accounting for competing risk (LGE: HR=3.69, 95% CI=1.28-10.62; RV GLS: HR=2.04, 95% CI=1.30-3.22). Adding RV GLS to the baseline model improved its prognostic value, with a c statistic improvement from 0.678 to 0.730. RV GLS hazard ratio remained significant in multivariate analysis after accounting for competing risk (HR=1.73, 95% CI=1.12-2.66) (Table 1). Conclusions: In NICM, RV GLS provides additional predictive value above LGE and clinical features for ICD intervention.

Disparities in Referral and Utilization of Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death.

Implantable cardioverter-defibrillators (ICDs) reduce mortality in patients with reduced left ventricular ejection fraction (LVEF). We investigated sex disparities in a contemporary Canadian population for utilization of primary prevention ICDs. This was a retrospective cohort study on patients with reduced LVEF admitted to hospitals from 2010 to 2020 in Nova Scotia (population= 971,935). There were 4406 patients eligible for ICDs: 3108 (71%) men and 1298 (29%) women. The mean follow-up time was 3.9 ± 3.0 years. Rates of coronary disease were similar between men and women (45.8% vs 44.0%; P= 0.28), but men had lower LVEF (26.6 ± 5.9% vs 27.2 ± 5.8%; P= 0.0017). The referral rate for ICD was 11% (n= 487), with 13% of men (n= 403) and 6.5% of women (n= 84) referred (P < 0.001). The ICD implantation rate in the population was 8% (n= 358), with 9.5% of men (n= 296) and 4.8% of women (n= 62) (P < 0.001) receiving the device. Men were more likely than women to receive an ICD (odds ratio 2.08, 95% confidence interval 1.61-2.70; P < 0.0001)). There was no significant difference in mortality between men and women (P= 0.2764). There was no significant difference in device therapies between men and women (43.8% vs 31.1%; P= 0.0685). A significant disparity exists in the utilization of primary prevention ICDs between men and women in a contemporary Canadian population.

The Uncertain Benefit from Implantable Cardioverter-Defibrillators in Nonischemic Cardiomyopathy: How to Guide Clinical Decision-Making?

Life-threatening dysrhythmias remain a significant cause of mortality in patients with nonischemic cardiomyopathy (NICM). Implantable cardioverter-defibrillators (ICD) effectively reduce mortality in patients who have survived a life-threatening arrhythmic event. The evidence for survival benefit of primary prevention ICD for patients with high-risk NICM on guideline-directed medical therapy is not as robust, with efficacy questioned by recent studies. In this review, we summarize the data on the risk of life-threatening arrhythmias in NICM, the recommendations, and the evidence supporting the efficacy of primary prevention ICD, and highlight tools that may improve the identification of patients who could benefit from primary prevention ICD implantation.