Primary Prevention ICD Research Articles

Risk stratification for ventricular tachyarrhythmia in patients with nonischemic cardiomyopathy

AbstractIntroductionThe implantable cardioverter defibrillator reduces mortality among patients with heart failure (HF) due to ischemic heart disease. Clinical trial data have called into question the benefit of an ICD in patients with HF due to nonischemic cardiomyopathy (NICM). We developed a risk stratification score for ventricular tachyarrhythmia (VTA) among patients with NICM receiving a primary prevention ICD.MethodsThe study population comprised 1515 patients with NICM who were enrolled in the landmark MADIT trials. Fine and Gray analysis was used to develop a model to predict the occurrence of VTAs and ICD therapies while accounting for the competing risk of non‐arrhythmic mortality. External validation was carried out in the RAID Trial population.ResultsFour risk factors associated with increased risk for VTA were identified: male sex, left ventricular ejection fraction ≤25%, no indication for cardiac resynchronization therapy with a defibrillator (CRT‐D), and Black race. A score was generated based on this model, and patients were stratified into low (N = 390), intermediate (N = 728), and high‐risk (N = 387) groups. The 5‐year cumulative incidences of VTA were 15%, 24%, and 42%, respectively. Application of score groups for the secondary endpoints of Fast VT or VF and Appropriate ICD Shock revealed similar findings. Recurrent event analysis yielded consistent results. The AUC in the validation cohort for the endpoint of Appropriate ICD Shock was 69.3.ConclusionsOur study shows that patients with NICM can be risk stratified using demographic and clinical variables and may be used when evaluating such patients for a primary prevention ICD.

Late gadolinium enhancement on cardiac MRI: A systematic review and meta-analysis of prognosis across cardiomyopathies

BackgroundLate gadolinium enhancement (LGE) on cardiac MRI has been shown to predict adverse outcomes in a range of cardiac diseases. However, no study has systematically reviewed and analyzed the literature across all cardiac pathologies including rare diseases. MethodsPubMed, EMBASE and Web of Science were searched for studies evaluating the relationship between LGE burden and cardiovascular outcomes. Outcomes included all-cause mortality, MACE, sudden cardiac death, sustained VT or VF, appropriate ICD shock, heart transplant, and heart failure hospitalization. Only studies reporting hazards ratios with LGE as a continuous variable were included. ResultsOf the initial 8928 studies, 95 studies (23,313 patients) were included across 19 clinical entities. The studies included ischemic cardiomyopathy (7182 patients, 33 studies), hypertrophic cardiomyopathy (5080 patients, 17 studies), non-ischemic cardiomyopathy not otherwise specified (2627 patients, 11 studies), and dilated cardiomyopathy (2345 patients, 14 studies). Among 42 studies that quantified LGE by percent myocardium, a 1 % increase in LGE burden was associated with life-threatening ventricular arrhythmias (LTVA) with a pooled hazard ratio of 1.04 (CI 1.02–1.05), and MACE with a pooled hazard ratio of 1.06 (CI 1.04–1.07). The risk of these events was similar across disease types, with minimal heterogeneity. ConclusionsDespite mechanistic differences myocardial injury, LGE appears to have a fairly consistent, dose-dependent effect on risk of LTVA, MACE, and mortality. This data can be applied to derive a patient's absolute risk of LTVA, and therefore can be clinically useful in informing decisions on primary prevention ICD implantation irrespective of the disease etiology.

Prospective assessment of risk factors for appropriate ICD intervention in patients with ischemic cardiomyopathy: results of PARCADIA trial

Abstract Background There is still a big unmet need for better risk stratification tools to identify patients at high risk for sudden cardiac death in the era of primary prevention ICD therapy. Scar burden on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging may be a risk marker for the prediction of ventricular arrhythmia in post-myocardial infarction (MI) patients. Purpose The aim of the PARCADIA trial was to assess whether scar characteristics, determined via LGE-CMR, or other baseline risk markers are associated with appropriate ICD therapy. Methods In this prospective, multi-center, clinical trial, we enrolled post-MI patients with an indication for de novo primary prevention ICD. Main exclusion criteria were indication for cardiac resynchronization therapy and NYHA class IV. Prior to the ICD implantation, LGE-CMR was performed to analyze the amount of scar tissue (LGE core mass + grey zone mass) and LV function / volumes. A 24h Holter recording was performed to collect information on potential triggers like premature ventricular beats (PVB) and sympathetic-vagal balance based on heart rate variability (HRV). Follow-ups were performed in-office every 6 months, including remote monitoring. Appropriate ICD therapy was used as primary endpoint and adjudicated by a clinical event committee. Results 199 patients were enrolled at 5 investigational sites in Europe. Patients mean age was 64.3 years, with a mean LVEF of 27.7 %, timing from the index MI was 9.1 years, and 42.7% received a primary PCI on index MI. After a median follow-up duration of 47.7 months, 23.1% of patients received appropriate ICD therapy. In 135 patients (67.8%), quality of LGE-CMR was sufficient for detailed analysis. The mean LGE core mass (20.5 vs. 19,7 g) and grey zone mass (10.5 vs. 11.4 g) was not different in patients with or without appropriate ICD therapy, also not when corrected for LV mass. However, LVEF (28.5 vs. 32.9 %) was lower, while diastolic myocardial mass (141 vs. 125 g), and end-diastolic volume (265.0 vs. 226.7 ml) were significantly higher in patients with appropriate ICD therapy. On 24h Holter the mean PVB burden (3695 vs. 1643 beats), and non-sustained ventricular tachycardia (12 vs. 0.9), were higher in patients with appropriate ICD therapy, while the HRV (96.1 vs. 113.1 SDNN) was lower. In univariate analysis the variables LVEF, timing to index MI, primary PCI on index MI, PVB burden and HRV appeared to be predictors for appropriate ICD intervention, while in multivariate analysis LVEF and PVB burden remained predictive. Conclusion In post-MI patients with appropriate ICD therapy, scar burden was not different from patients without appropriate ICD therapy. Only LVEF and PVB burden were independent predictors of increased arrhythmogenicity. Improved CMR analysis on scar characteristics (conduction channels) to identify potential arrhythmogenic regions might be the topic for future research.

Echocardiographic evaluation of cardiac remodelling in a cohort of patients with heart failure and reduced ejection fraction treated with dapagliflozin

Abstract Background Several mechanisms have been proposed to explain SGLT2 inhibitors’ (SGLT2i) beneficial effects in patients with heart failure (HF), but their exact mode of action in this setting is not fully understood. Pivotal randomised clinical trials regarding this class of drugs in HF setting have not reported echocardiographic data regarding potential cardiac positive remodelling. Objectives To assess the effects of dapagliflozin treatment initiation on cardiac remodelling in patients with HF and reduced ejection fraction (HFrEF), with a focus on left ventricular performance and atrial volumetry. Methods In this retrospective observational study, we analysed data from 94 patients with HFrEF in whom dapagliflozin had been prescribed as part of HF treatment optimization. Inclusion criteria were: age > 18 years; ongoing optimal medical therapy (OMT) for HF according to 2021 ESC HF guidelines (except for SGLT2i); transthoracic echocardiogram within 30 days of baseline assessment demonstrating a left ventricular (LV) ejection fraction (EF) <40%; comprehensive assessment at 6 months with clinical, laboratory and echocardiographic data. Results Patients (mean age 71.7 ± 9.8, 76% males, coronary artery disease as HFrEF main aetiology in 66%) showed significant cardiac remodelling after dapagliflozin initiation, specifically in terms of stroke volume index (SVi, +9.7 ml/m2, p<0.001), LVEF (+5.1%, p<0.001), LV end-diastolic volume (LV EDV) index (-8.4 ml/m2, p<0.001), left atrial (LA) volume index (-3.9 ml/m2, p=0.026), and LV mass index (LVMi, -12.9 gr/m2, p=0.004). BNP tended to significantly decrease (-168.6 ng/L, p=0.025). Percentage of patients with an indication for ICD implantation in primary prevention went from 36.2% to 8.5%, p<0.001. We did not observe significant differences in terms of mitral regurgitation (MR) grading at follow-up (in particular, the proportion of patients with severe MR remained approximately stable: 7% vs 4%, p=0.86). We did not observe any change in diastolic function measured by E/e’ ratio (mean difference -0.6; 95% CI -2.2 to 0.9, p=0.41). Conclusions Treatment with dapagliflozin resulted in positive remodelling in our cohort of patients with HFrEF in terms of chamber volumes, contractility parameters (and this was not explained by an improvement in MR severity) and LVMi. There was a significant decrease in natriuretic peptide as well as in the proportion of patients with primary prevention ICD indication. Our findings highlight the need of further data to fully elucidate the exact mechanism that leads to LA and LV positive remodelling with SGLT2i.Figure 1.Change in TTE Parameters

Implantable cardioverter defibrillator therapy in paediatric patients for primary vs. secondary prevention.

The decisions about placing an ICD in a child are more difficult than in an adult due to longer expected lifespan and the complication risk. Young patients gain the most years from ICDs, despite higher risk of device-related complications. The secondary prevention ICD indication is clear, and device is implanted regardless of potential complications. For primary prevention, risk of sudden cardiac death and complications need to be evaluated. We aimed to compare outcomes for primary and secondary prevention ICDs. Retrospective nationwide cohort study including paediatric patients identified from the Danish ICD registry with ICD implanted at an age ≤ 15 from 1982-21. Demographics, complications (composite of device-related infections or lead-failure requiring re-operation, mortality because of arrhythmia, or unknown cause), and mortality were retrieved from medical charts. Endpoint was appropriate therapy (shock or anti-tachycardia pacing for ventricular tachycardia or fibrillation). Of 72 receiving an ICD, the majority had channelopathies (n = 34) or structural heart diseases (n = 28). ICDs were implanted in 23 patients for primary prevention and 49 for secondary prevention, at median ages of 13.8 and 11.6 years (P-value 0.01), respectively. Median follow-up was 9.0 (interquartile ranges: 4.7-13.5) years. The 10-year cumulative incidence of first appropriate therapy was 70%, with complication and inappropriate therapy rates at 41% and 15%, respectively. No difference was observed between prevention groups for all outcomes. Six patients died during follow-up. In children, two-thirds are secondary prevention ICDs. Children have higher appropriate therapy and complication rates than adults, while the inappropriate therapy rate was low.

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

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

VDD-ICD Implantation in a Patient with Dextrocardia and Corrected Transposition of the Great Arteries

We present the case of a 52-year-old female patient on optimal medical therapy (OMT) for heart failure with severely reduced ejection fraction. She was diagnosed with dextrocardia and congenital corrected transposition of the great arteries (ccTGA) by echocardiography. Despite 3 months of OMT and a persisting NYHA II functional state, she was referred for primary prevention ICD implantation. At admission echocardiography revealed a hypertrophic systemic ventricle with an ejection fraction of 27%. Cardiac CT confirmed ccTGA, dextrocardia, a normal extracardiac and epicardial venous system. Coronary artery disease was excluded. Our team opted for left-sided VDD-ICD implantation in case of a need for AV-synchronous pacing and to enhance arrhythmia discrimination. An active fixation shock lead was placed in the mid-septal region of the functional right ventricle. The defibrillation threshold test (DFT) was successful at 20 J. No periprocedural complications were observed. At the 12-month ambulatory visit, device interrogation showed good function, no detected arrhythmias, and no antitachycardia therapy was delivered. Preoperative imaging is essential prior to any invasive cardiac procedure in patients with congenital heart disease. Performing a DFT test at adult congenital heart disease patients may be reasonable.

Predicting long-term survival after de novo cardioverter-defibrillator implantation for primary prevention: A population based study

BackgroundImplantable cardioverter-defibrillators (ICDs) reduce the risk of sudden cardiac death in patients with left ventricular dysfunction. While short-term mortality benefit of ICD insertion has been established in landmark randomized controlled trials, little is known about the long-term outcomes of patients with ICDs in clinical practice. In this paper, we describe the long-term survival of patients following de novo ICD implantation for primary prevention in clinical practice and determine the factors which help predict survival after ICD implant. MethodsRetrospective population-based study of all patients receiving a de novo ICD for primary prevention in Ontario, Canada from 2007 to 2011 using the Ontario ICD Database housed within ICES. Simple random selection was used to split the population into a derivation and internal validation cohort in a ratio of 2:1. Cox proportional hazards regression was used to determine predictors of interest and predict 10-year survival, model performance was assessed using calibration and validation. ResultsIn the derivation cohort (n = 3399), mean age was 65.3 years (standard deviation [SD] = 11.0), 664 patients were female (19.5 %) and 2344 patients (69.0 %) had ischemic cardiomyopathy. Ten year survival was 45.7 % (95 % confidence interval [CI] 44.0 %–47.4 %). The final prediction model included age, sex, disease factors (ischemic vs nonischemic cardiomyopathy, left ventricular ejection fraction) and patient factors (symptoms, comorbidities), and biomarkers at the time of ICD assessment. This model had good discrimination and calibration in derivation (0.79, 95 % CI 0.77, 0.81) and validation samples (0.78, 95 % CI 0.76, 0.79). ConclusionsA combination of demographic and clinical factors determined at baseline can be used to predict 10-year survival in patients with implantable cardioverter-defibrillators with good accuracy. Our findings help to identify individuals at risk of long-term mortality and may be useful in targeting future prevention strategies to enhance longevity in this high-risk population.

Subcutaneous versus transvenous ICDs: a population-level comparison of incidence, patient characteristics, and complications of S-ICDs, ICDs, and CRT-Ds in a nationwide Dutch cohort (2018-2020)

Abstract Background Subcutaneous implantable cardioverter-defibrillators (S-ICDs) have emerged as a safe and effective alternative to ICDs for the prevention of sudden cardiac death. Compared to ICDs, S-ICDs aim to reduce morbidities associated with the transvenous lead including lead dislocation and infection. Limited evidence exists for the utilization, patient selection, and complications of S-ICDs in current real-world clinical practice. Purpose Our aim was to compare the implantation rate, patient characteristics, and complications of patients who underwent S-ICD, ICD, and CRT-D implants and replacements in the Netherlands from 2018 to 2020. Methods The Netherlands Heart Registration includes all adult patients who underwent an ICD implant or replacement at 28 hospitals in the Netherlands (2018-2020). Annual crude, age-, and sex-standardized incidence rates were assessed with Poisson regression models with robust variances. Patient characteristics and complications were compared between ICD types with ANOVA tests. Determinants of complications were identified with multivariable logistic regression models. Results Of 17,080 patients who had a de novo ICD implant (n=10,317) or replacement (n=6,763) in the Netherlands (2018-2020), 1408 (8.2%) patients had an S-ICD, 9441 (55.3%) patients received an ICD only, and 6231 (36.5%) patients received a CRT-D. The incidence of de novo S-ICDs were stable over time, however the incidence of de novo ICD only and CRT-D implants decreased by 5% and 11%, respectively (p<0.05 for both; Figure 1). Patients who received S-ICDs were younger (53 years, IQR 41-62) than ICD (66 years, IQR 57-73) and CRT-D (70 years, IQR 62-75) patients (p<0.05). A greater proportion women had S-ICDs (25.0%) and CRT-Ds (26.7%) implanted compared to ICDs (19.9%) (p<0.05). Further, less atrial fibrillation patients had S-ICDs (21.6% vs ICD 30.9%, and CRT-D 32.4%). ICDs for primary prevention were implanted in 56.4%, 48.4%, and 81.2% of S-ICD, ICD, and CRT-D patients, respectively (p<0.05). The incidence of lead dislocations was less among S-ICD patients compared to ICD and CRT-D patients (p<0.001; Figure 2). There was no difference detected for other complications or long-term mortality (p>0.05 for all; Figure 2). Infections in S-ICD patients [aOR 0.2 (95% CI 0.1-0.9)] and in-hospital bleeding for CRT-D patients [aOR 0.4 (95% CI 0.2-0.9)] decreased among patients who underwent an ICD implant in recent years. In addition, advancing age was identified as a risk factor for in hospital bleeding in S-ICD patients [aOR 1.1 (95% CI 1.0-1.2)] and for pneumothorax in CRT-D patients [aOR 3.6 (95% CI 2.0-6.8)]. Conclusion In real-world practice, S-ICDs were implanted in younger patients with fewer comorbidities and portended a lower risk of lead dislodgement than ICDs and CRT-Ds; however, the population-level implantation rate of S-ICDs did not vary between 2018 to 2020 in the Netherlands.

Has the use of concomitant cardiac medications improved over time in primary prevention ICD patients? Insights from the APPRAISE ATP study

Abstract Introduction Patients (pts) implanted with an ICD for a primary prevention (PP) typically receive concomitant medications (meds) to treat LV dysfunction. However, It is not well established whether compliance with guideline-directed medical therapy (GDMT) has improved over time in this population. Methods Data were drawn from the MADIT-RIT (2009-2012) and APPRAISE ATP (2016-present) studies. Both studies were global in scope and enrolled pts who were implanted with an ICD for PP indications. Meds prescribed at baseline were compared between the two studies. Meds of interest included: evidence-based beta blockers [(BB-EV) defined as carvedilol, metoprolol, and bisoprolol], ACE inhibitors, ARBs, ARNIs, and mineralocorticoid receptor antagonists (MRA). SGLT2i were introduced into GDMT after the study APPRAISE ATP started and were not included. Meds were analyzed both individually and in combination as GDMT, defined as joint use of BB-EV, ACE/ARB/ARNI, and MRA. Differences were compared with a t-test for continuous variables, a Chi-square test for categorical data and a Cochran-Armitage trend test for ordinal categorical data. Results Demographics for the two studies were compared for pts who received ICDs in MADIT-RIT (n=742) and APPRAISE ATP (n=2627 enrolled with n=2596 randomized) and are shown in the table below. When compared to MADIT-RIT, APPRAISE ATP pts were significantly older with a greater prevalence of diabetes. Comparison of baseline meds are shown in both the table and in the figure. Although BB-EV and ACE/ARB use was slightly but significantly lower in APPRAISE ATP, these declines were offset by a significant increase in MRA use in APPRAISE ATP. A marked shift was seen over time with significant decline in use of ACE-I that was matched by a significant increase in use of ARBs, either alone or in combination with ARNIs. When considering meds used in combination for GDMT, pts in APPRAISE ATP were significantly more likely to meet GDMT recommendations than pts who were enrolled in MADIT-RIT (36.7% vs 27.2%, respectively, p<0.001). Conclusions In the APPRAISE ATP study, compliance with GDMT in PP ICD pts has significantly improved when compared to the MADIT-RIT study conducted 10 years previously. These changes have been characterized by greater use of MRAs as well as a shift away from ACE inhibitors towards use of ARBs and ARNIs. Although there was considerably greater compliance with GDMT, with approximately one third of pts fulfilling GMDT, opportunities still remain for improvement. Further investigation is needed to determine what influence greater compliance with GDMT may have on improved clinical outcomes such as reductions in VT/VF event rates and all-cause mortality.

Risk factors for first and recurrent ICD therapy in primary and secondary prevention patients with an implantable cardioverter defibrillator

Abstract Introduction Implantable cardioverter-defibrillators (ICD) are used to prevent sudden cardiac death in patients with elevated risk of life-threatening arrhythmia. Medical treatment of heart disease and the population of ICD carriers have changed since the pivotal studies 20 years ago, sparking a need for improved ICD candidate selection and identification of risk factors for ICD therapy. Purpose This study aimed to examine risk factors associated with incident and recurrent ICD shock. Methods This single-center, prospective registry-based study examined patients with ICD for primary or secondary prevention (PP, SP) implanted between January 2010 and January 2020. Outcomes were appropriate (ADC) and inappropriate (IADC) ICD shock. Supplementary analyses for the risks of recurrent shock were conducted if incident therapy occurred. Results Overall, 2997 patients were analyzed (median follow-up 6.5 years, mean age 63.8 years±12.7, 20% female, 27% CRT-D carriers and 47.8 % SP). A total of 386(13%) and 85(2.8%) experienced ADC and IADC, respectively and 143(37%) and 17(20%) recurrent therapies, respectively. Event rates were 2.6(2.4-2.9) [PP 1.7 (1.4-2.0); SP 3.7(3.3-4.2)] and 0.5 (0.4-0.7) [PP 0.4(0.2-0.5); SP 0.7(0.5-0.9)] per 100 person-years for incident ADC and IADC, respectively. For recurrent ADC and IADC, event rates were 14.6(12.3-17.2) [PP 14.1(10.1-19.2); SP 14.7(11.9-17.8)] and 2.9(1.3-5.4) [PP 2.6(0.5-7.7); SP 3.0(1.1-6.6)], respectively. Figure 1 shows cumulative incidences for PP and SP. Females had a lower risk of incident ADC (HR 0.68 [95% CI 0.50;0.92] p=0.01) overall and when SP (HR 0.66 [95% CI 0.45;0.97] p=0.04), as did CRT-D overall (HR 0.60 [95% CI 0.45;0.82] p=0.001) and in SP (HR 0.42 [95% CI 0.24;0.74] p=0.003). Previous revascularization was associated with a lower risk of incident IADC (HR 0.58 [95% CI 0.36;0.94] p=0.03) overall and in SP (HR 0.51 [95% CI 0.28;0.93] p=0.03). Left ventricular ejection fraction (LVEF) <35 and BMI >30 in SP patients were associated with increased risk of incident ADC and IADC respectively (HR 1.38 [95% CI 1.04;1.84] p=0.03) and HR 2.48 [95% CI 1.16;5.32] p=0.02). Association with higher risk of recurrent ADC was only seen in BMI <18.5 for SP patients (HR 87.37 [95% CI 8.43;905.72] p<0.001), no associations for recurrent IADC were observed. No interactions between SP/PP and risk factors, except for BMI>30 on IADC (p for interaction=0.01) occurred. PP (HR 0.38 [95% CI 0.16;0.89] p=0.02) and SP (HR 1.77 [95% CI 1.04;3.03] p=0.03). Conclusion This large single-center study found higher rates of incident and recurrent ICD shock in SP versus PP. Female sex and CRT-D were associated with lower risk of ADC, previous revascularization with increased risk of IADC. BMI>30 and reduced LVEF were associated with increased risk of incident ADC and IADC respectively. Further contemporary studies are needed to cast light on the clinical implications of risk factors.

Changes in study enrollment of patients with non-ischemic cardiomyopathy receiving an ICD for primary prevention: Insights from the APPRAISE ATP study

Abstract Introduction The DANISH study called into question the effectiveness of the ICD in patients (pts) with non-ischemic cardiomyopathy (NIC) and resulted in a downgrade in ESC guidelines from Class I to Class IIA. The effect of these findings on implantation of ICDs in NIC pts in clinical studies has not been well established. Methods Two clinical studies were analyzed before and after the publication of DANISH: MADIT-RIT (2009-2012) and APPRAISE ATP (2017-present). These two studies enrolled globally and implanted ICDs in pts with primary prevention (PP) indications. The proportion of pts with NIC were analyzed between the two studies, both globally and by region: North America (NA) and European Union (EU). In addition, the APPRAISE ATP study was divided into halves to determine if any changes were observed whilst the study was in progress. Continuous variables were analyzed with a t-test and categorical variables were analyzed with a Chi-square test. Due to small numbers, implanted pts outside NA and the EU were not entered into the analysis. Results Demographics for the NIC subgroups are shown in the table below [MADIT-RIT (n=284) and APPRAISE ATP (n=1084)]. When compared to MADIT-RIT, pts in APPRAISE ATP were significantly older, had a higher mean LVEF, and greater prevalence of AF and diabetes. Globally, the proportion of pts with NIC who received ICDs was unchanged between the current APPRAISE ATP study and MADIT-RIT 10 years previously (38.1% vs 39.3%, p=0.91). When analyzed by geography, there was no change in North America (38.0% vs 41.6%, p=0.27). In Europe, however, there was a drop in enrollment of NIC ICD pts from 38.6% in MADIT-RIT to 29.1% in APPRAISE ATP. This decline was 24.6% in relative terms and approached, but did not achieve, statistical significance (p=0.074). Implant rates in NIC ICD pts were stable overall when comparing the first half of APPRAISE ATP to its second half. Rates were also stable across both halves in NA and while implant rates of NIC ICD pts appeared to rebound in the second half in the EU, that late increase was not statistically significant. Conclusions The results of the DANISH study appear to have had a limited global impact on enrollment of NIC pts requiring implant of a PP ICD into the APPRAISE ICD clinical study. Whilst there was no change in North America before and after DANISH, there is a signal in the data that investigators in the EU may have restricted implants initially but eventually relaxed as time progressed. Further investigation is needed to confirm whether physicians in general practice have altered their referral patterns.

Sex-differences in ventricular tachyarrhythmia events in patients with implantable cardioverter defibrillator and prior ventricular tachyarrhythmias

Abstract Background Women have been previously shown to be at a lower risk of ventricular tachyarrhythmia (VT) events in ICD trials, however, more contemporary data on the risk of VT/VF and death by sex in patients with prior VT/VF are lacking. Objective We aimed to assess sex-differences in ICD-treated VT/VF events and all-cause mortality in patients in the Ranolazine in High-Risk ICD Patients (RAID) trial. Patients were either implanted for secondary prevention or primary prevention ICD indications but experienced VT/VF before enrolment. Methods The RAID trial enrolled high-risk ICD patients with ischemic or non-ischemic cardiomyopathy, randomized to ranolazine or placebo. This analysis focused on patients with prior VT/VF. Sex-differences in VT/VF requiring ATP or shock were evaluated using Kaplan-Meier analysis, Fine and Grey, and Cox models in an intention to treat analysis. All VT/VF episodes were centrally adjudicated. Results There were 124 women (17%) out of 714 subjects analysed. Women were younger (60 vs. 65 years, p<0.001), more often non-ischemic (70% vs. 37%, p<0.001), less often had hypertension (69% vs. 78%, p=0.045) and diabetes (19% vs. 34%, p=0.002). Compared to men, women were at a significantly lower risk of VT/VF/Death (HR=0.67, [95% CI, 0.46-0.96], p=0.029), lower risk of VT/VF (HR=0.68, [95% CI, 0.46-1.00], p=0.049), lower risk of VT/VF treated with ATP (HR=0.59, [95% CI, 0.38-0.92], p=0.019), and lower risk of VT/VF treated with ICD shock (HR=0.54, [95% CI, 0.31-0.96], p=0.035). The risk of recurrent VT/VF was also significantly lower in woman (HR=0.35 [95% CI, 0.26-0.48], p<0.001). Hazard ratio for death was similar to the other endpoints, (HR=0.61, [95% CI 0.30-1.22] p=0.162) but did not reach statistical significance, most probably related to low statistical power due the relatively small number of death events among women. The effect of ranolazine on endpoints did not differ by sex. Conclusions Women with a history of prior VT/VF and managed with an ICD/CRT-D experienced a lower risk recurrent VT/VF requiring device therapy as compared with men. The risk of mortality showed a similar trend although did not reach significance.

Abstract 15656: Early Recurrence of Ventricular Tachycardia and the Impact of Radiofrequency Ablation on Success of ICD Therapy

The early success of radiofrequency ablation (RFA) and impact on ICD delivered therapy (including the need for antitachycardia pacing (ATP) or ICD shock) after the procedure, due to recurrent VT events, is still not clear. Hypothesis: Recurrences of VT during 12 months of follow up (FU) after RFA are associated with the need for ICD therapy (successful ATP or need for ICD shock) and related to pre-procedural ATP success or failure. Methods: We analyzed the data of 141 ventricular arrhythmia patients who underwent RFA during 2019 - 2022 by identifying 54 (38.3%) patients with monomorphic VT and implanted ICDs. Age - 69.54±10.04 years , 52 (96.3%) males, BMI - 29.1±6.2; 27 (50.0%) patients - ICM; 51 (94.4%) used antiarrhythmics and 40 (82.1%) have failed; beta-blockers use - 47 (87.0%). 20 (37.0%) had an ICD for primary prevention. LVEF - 39.2±13.8%, VT cycle - 350±80 ms. VT storm - in 46 (85.2%). Results: Out of 54 included patients, only 34 (63%) had no recurrent VT events during FU post-RFA procedure. 20 (37.0%) experienced recurrent VT events and needed ICD therapy: 8 (40.0%) responded to ATP, whereas 12 (60.0%) failed ATP and required an ICD shock. Patients’ response to ICD delivered therapy was compared between two groups of patients: 1) pre-ablation ATP failure (n=40) and 2) pre-ablation ATP success (n=14). In pre-ablation ATP failure group, 23 (57.5%) patients had no recurrent VT events, 5 (12.5%) successfully responded to ATP and 11 (27.5%) failed ATP requiring ICD shock. In the pre-ablation ATP success group, 9 (64.5%) patients had no recurrent VT, 3 (21.4%) responded to ATP, and only 1 (7.14%) required ICD shock and no VT storm episodes, whereas 12 (30%) of patients with pre-procedural ATP failure had VT storm (IQR= 0.0, 0.0, vs 1.0, 5.0 respectively; p=0.019). Patients with recurrent VT events had higher BMI then patients with no recurrent VT: 32.9±5.4 vs 28.0±6.0, p< 0.033. The pre-ablation ATP failure group had a greater proportion of hemodynamically unstable VT induced during RFA (56.7% vs 23.1%; p=0.043). Conclusion: The success of ATP after RFA was associated with pre-procedural ATP response and patients with lower BMI had less recurrent VT events. Overall, pre-ablation ATP failure for VT termination may identify patients with increased risk of failure to ATP therapy.

Abstract 14463: Beyond Sarcomere Mutations Plakophilin-2 and Familial Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous disorder with diverse clinical presentation, course and outcomes. It is commonly caused by mutations in sarcomeric genes. Non-sarcomeric gene mutations have been associated with HCM in certain metabolic and storage diseases. Pathogenic mutations in plakophilin-2 (PKP2) gene have been associated with enhanced desmosomal protein degradation and linked to arrhythmogenic right ventricular cardiomyopathy (ARVC), Brugada syndrome and dilated cardiomyopathy. We report an association between PKP2 gene mutation and familial HCM. Case presentation: A 65-year-old man with family history of HCM (maternal grandfather, 2 aunts and an uncle) presented with dyspnea on exertion (NYHA class II-III) and pedal edema. Echo showed severe LVH, mid-cavitary obstruction and LV apical aneurysm. Cardiac MRI confirmed findings (Figure:A and B) and additionally showed significant late gadolinium enhancement (Figure:C and D, >20% of LV myocardium). Extended ambulatory heart monitor detected frequent runs on non-sustained ventricular tachycardia. A primary prevention ICD was implanted. Genetic testing identified a pathogenic mutation [c.1237C>T (p.Arg413*)] in exon 5 of PKP2 gene resulting in premature translational stop signal and disrupted desmosomal protein plakophilin-2. Family screening (Figure:E) identified a sister with positive results who also had non-obstructive HCM (Figure:E). Discussion: We present a family with typical presentations of HCM and no phenotypic evidence of ARVC. This novel observation provides evidence for pleiotropic model of complex genotype-phenotype interactions through nonlinear networks. Further evidence would be needed to understand potential molecular basis of hypertrophic signaling in PKP2 gene mutation.

Abstract 16010: Sudden Death in the Systemic Right Ventricle: Single Center Study of Dextro-Transposition of the Great Arteries Palliated With Atrial Switch

Introduction: The incidence and risk factors for sudden cardiac death (SCD) in patients with systemic right ventricle (sRV) and D-TGA palliated with atrial switch procedures is not well understood. Methods: This cohort was examined retrospectively for the composite end point of SCD, sustained ventricular tachycardia (VT) >30 s or appropriate ICD therapy for VT. Clinical characteristics of those with and without the end point were compared using the Kruskal-Wallis or Chi-square test as appropriate. Results: The composite end point occurred in 15 of 148 (10%) patients (63.5% male) at a mean age of 36.4 (SD 10.3) years. SCD occurred in 6 patients (n=2 successfully resuscitated), sustained VT in 6 patients and ICD therapy for VT in 3 patients who had previously received a primary prevention ICD. Patients with SCD/VT had lower sRV ejection fraction (EF) compared to patients without SCD/VT [28±11 vs 40±10%, P<0.001]. The odds ratio of SCD/VT in patients with sRVEF≤35% compared to sRVEF>35% was 13.3 (95% CI 2.8 - 64.4). Kaplan Meier analysis of time to SCD/VT stratified by sRV EF is presented in figure. QRS duration, QRS fragmentation, QTc and history of systemic AV valve surgery were not significantly associated with SCD/VT. Non-sustained ventricular tachycardia (NSVT) on Holter monitoring occurred more frequently in SCD/VT patients (80 vs 39%, p=0.003). All 11 survivors of SCD/VT received an ICD; appropriate ICD therapy occurred in 27% of these patients during follow-up. Conclusion: SCD or VT occurred in one-tenth of D-TGA patients palliated with atrial switch, predominantly in 3 rd and 4 th decade of life. Reduced sRV EF was the most important association and ICD implantation for primary prevention of SCD is a reasonable consideration in those with reduced sRV EF.

Abstract 16974: Sudden Cardiac Death With Heart Failure Despite Improvement in LV Ejection Fraction: A Population-Based Study

Introduction: Individuals with heart failure (HF) and severely reduced LVEF (≤35%) have increased risk of SCD and qualify for primary prevention ICD implantation. Guideline-directed medical therapy can improve LVEF in ICD patients but influence on SCD risk remains controversial. Hypothesis: In a subgroup of HF patients, improvements in LVEF may not eliminate risk of SCD.Aim: To identify and characterize a subgroup of HF patients who suffer SCD despite improvements in LVEF. Methods: From a large, prospective population-based study of SCD in the Northwest US (population ~1 million, 2002-2018), we identified all consecutive patients with an established diagnosis of HF and LVEF≤35%. In the sub-group of patients with at least 2 prior LVEF evaluations (earliest and latest in relation to SCD), individuals with significant improvement in LVEF over time (latest LVEF >35%) were compared to those without improvement in LVEF (latest LVEF ≤35%). Results: A total of 1622 individuals suffered SCD with a known diagnosis of HF (65% male, age 72±14) of which 434 had at least 2 LVEF evaluations over time prior to their SCD. Of these 100 (23%) had LVEF ≤35% at their earliest evaluation (mean LVEF 27±6). A subgroup of 46% (n=46) had significant improvement in LVEF between earliest vs latest evaluation (28±6 vs. 49+9, by 20±10, p<0.001) with no improvement observed in the remainder (54%, 25±6 vs. 24±7, by -1±7, p = 0.23). Comparisons of the clinical profile (demographic, coronary disease, comorbidities and medications) did not yield any identifiable differences between the subgroups with and without improvement in LVEF (Table; p>0.05 for all). Conclusions: Approximately half of individuals with SCD and a history of HF and LVEF ≤35% had significant improvements in LVEF, but this group could not be distinguished from those without improvements in LVEF by readily available clinical variables. These findings highlight the need for novel markers of SCD risk beyond the LVEF for this subset of HF patients.

Clinical profile and outcomes of pediatric hypertrophic cardiomyopathy in a South Indian tertiary care cardiac center: a three decade experience

IntroductionAlthough much research has been done on adult hypertrophic cardiomyopathy, data on pediatric hypertrophic cardiomyopathy is still limited.Methods and resultsThe study enrolled all patients with cardiomyopathy who presented to us between 1990 to 2020 and were younger than 18 yrs. During the thirty-year study period, we identified 233 cases of pediatric cardiomyopathy. Sixty-three cases (27%) had hypertrophic cardiomyopathy. Out of the 63 HCM cases, 12% presented in the neonatal period and 37% presented in the first year of life. The median age of presentation was 7 yrs (Range 0.1–18 yrs). Sixteen patients had proven syndromic, metabolic, or genetic disease (25%). LV outflow obstruction was present in 30 patients (47%). Noonan syndrome was present in 9 of the 63 patients (14%). Dyspnea on exertion was the most common mode of presentation. Cardiac MRI was done in 28 patients, out of which 17 had late gadolinium enhancement (LGE). Mid myocardial enhancement was the most common pattern. Four patients had LGE of more than 15%. Over a mean follow-up period of 5.6 years (0.1–30 years), twenty-one were lost to follow-up (33%). Among the patients whose outcome was known, eleven died (26%), and thirty-one (73%) were alive. The 5-year survival rate of HCM patients was 82%, and the 10-year survival rate was 78%. Seven died of sudden cardiac death, three from heart failure, and one from ventricular arrhythmias. Sustained ventricular arrhythmias were seen in three patients and atrial arrhythmias in two. First-degree AV block was seen in 10 patients (15%) and bundle branch blocks (BBB) in five (8%). Eight patients required ICD or transplant (12.7%). Two patients underwent ICD for primary prevention, and one underwent PPI for distal AV conduction disease. Among the various clinical, echocardiographic, and radiological risk factors studied, only consanguinity showed a trend towards higher events of death or ventricular arrhythmias (P-value 0.08).ConclusionMore than one-third of our HCM cohort presented in infancy. LV outflow tract obstruction is common (47%). Mid myocardial enhancement was the most common pattern of late gadolinium enhancement. SCD was the most common cause of death. The outcome in our HCM cohort is good and similar to other population cohorts. Only Consanguinity showed a trend towards higher events of death or ventricular arrhythmias.

ICD/CRT-D Registry Ain Shams University Hospitals

Abstract Background The idea of the ICD registry was prompted from the National Coverage Decision that was published by the Centers for Medicare and Medicaid Services (CMS) in 2005 and based on the Sudden Cardiac Death in Heart Failure Trial, Ain Shams University Hospitals aim to take the lead by documenting the first ICD/CRT-D Registry in Egypt. Aim of the Work To capture the characteristics, treatments, and outcomes of patients receiving ICDs to improve care for patients receiving ICDs and CRT-Ds in Egypt. Methods 102 consecutive patient that received an ICD/CRT-D (initial or generator change) for primary or secondary prevention of SCD and came for ICD/CRT-D follow up at Ain Shams University hospitals pacemaker outpatient clinics in a timeline of one year (7-2019 till 11-2020). Results Males were around two thirds of cases (68.6%), and more than half of cases (52%) were smokers. Implantation for primary prevention of SCD was in 58.8% of patients. Most of cases had their ICDs follow-up at a time between 1 to 3 years after implantation. HFrEF was significantly more common in primary prevention group (93.3%) of patients of primary prevention group, while IsHD was the most common comorbidity in patients that had ICD implantation for secondary prevention of SCD (66.7% of them). Total complication rate was 6.86% including, pocket hematoma occurred in 2.9% of cases, and lead dislodgment that required repositioning without a plan to add a transvenous lead occurred in 3.9% of cases. Beta Blockers and Amiodarone were the most common drugs used among patients as regard 88.2% and 65.7% respectively. VTs and NSVTs were the most frequent post implantation events among the studied cases 45.1% and 42.2% respectively. 52% of patients had ATP therapy to events, Failed ATP therapy occurred in 60% of them. 33.3% of patient received ICD shock therapy, Inappropriate Shocks was in 20.6% of them. 50.9% of the patients had a bradycardia pacing as about 34% of patient had CRT-D for pump failure. VF detection zone interval was significantly longer in primary prevention group. No significant differences according to implantation indication regarding VT2 zone interval. Regarding VT1 zone; monitor only was the mainly action in 58.7% of patients. Only 20.6% of patients had VT1 zone off. Conclusion This observational and descriptive study provides strong evidence that ICD has an effective role to improve survival in primary and secondary prevention of SCD. We noticed increase in implantation rate of ICD for primary prevention of SCD who gain great benefits from the device later on, minimal complication rate of ICD implantation.

Follow-up of CRT-D patients downgraded to CRT-P at the time of generator exchange.

Some patients with cardiac resynchronisation therapy (CRT) experience super-response (LVEF improvements to ≥50%). At generator exchange (GE), downgrading (DG) from CRT-defibrillator (CRT-D) to CRT-pacemaker (CRT-P) could be an option for these patients on primary prevention ICD indication and no required ICD therapies. Long-term data on arrhythmic events in super-responders is scarce. CRT-D patients with LVEF improvement to ≥50% at GE were identified in four large centres for retrospective analysis. Mortality, significant ventricular tachyarrhythmia and appropriate ICD-therapy were determined, and patient analysis was split into two groups (downgraded to CRT-P or not). Sixty-six patients (53% male, 26% coronary artery disease) on primary prevention were followed for a median of 129 months [IQR: 101-155] after implantation. 27 (41%) patients were downgraded to CRT-P at GE after a median of 68 [IQR: 58-98] months (LVEF 54% ± 4%). The other 39 (59%) continued with CRT-D therapy (LVEF 52% ± 6%). No cardiac death or significant arrhythmia occurred in the CRT-P group (median follow-up (FU) 38 months [IQR: 29-53]). Three appropriate ICD-therapies occurred in the CRT-D group [median FU 70 months (IQR: 39-97)]. Annualized event-rates after DG/GE were 1.5%/year and 1.0%/year in the CRT-D group and the whole cohort, respectively. No significant tachyarrhythmia were detected in the patients downgraded to CRT-P during follow-up. However, three events were observed in the CRT-D group. Whilst downgrading CRT-D patients is an option, a small residual risk for arrhythmic events remains and decisions regarding downgrade should be made on a case-by-case basis.