Usefulness of the MAGGIC Score in Predicting the Competing Risk of Non-Sudden Death in Heart Failure Patients Receiving an Implantable Cardioverter-Defibrillator: A Sub-Analysis of the OBSERVO-ICD Registry

The role of prognostic risk scores in predicting the competing risk of non-sudden death in heart failure patients with reduced ejection fraction (HFrEF) receiving an implantable cardioverter-defibrillator (ICD) is unclear. To this goal, we evaluated the accuracy and usefulness of the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score. The present analysis included 1089 HFrEF ICD recipients enrolled in the OBSERVO-ICD registry (NCT02735811). During a median follow-up of 36 months (1st–3rd IQR 25–48 months), 193 patients (17.7%) experienced at least one appropriate ICD therapy, and 133 patients died (12.2%) without experiencing any ICD therapy. The frequency of patients receiving ICD therapies was stable around 17–19% across increasing tertiles of 3-year MAGGIC probability of death, whereas non-sudden mortality increased (6.4% to 9.8% to 20.8%, p < 0.0001). Accuracy of MAGGIC score was 0.60 (95% CI, 0.56–0.64) for the overall outcome, 0.53 (95% CI, 0.49–0.57) for ICD therapies and 0.65 (95% CI, 0.60–0.70) for non-sudden death. In patients with higher 3-year MAGGIC probability of death, the increase in the competing risk of non-sudden death during follow-up was greater than that of receiving an appropriate ICD therapy. Results were unaffected when analysis was limited to ICD shocks only. The MAGGIC risk score proved accurate and useful in predicting the competing risk of non-sudden death in HFrEF ICD recipients. Estimation of mortality risk should be taken into greater consideration at the time of ICD implantation.

Efficacy and Safety of Appropriate Shocks and Antitachycardia Pacing in Transvenous and Subcutaneous Implantable Defibrillators: An Analysis of All Appropriate Therapy in the PRAETORIAN trial

Background: The PRAETORIAN trial showed non-inferiority of the subcutaneous implantable cardioverter-defibrillator (S-ICD) compared to the transvenous ICD (TV-ICD) with regard to inappropriate shocks and complications. In contrast to the TV-ICD, the S-ICD cannot provide antitachycardia pacing (ATP) for monomorphic ventricular tachycardia (VT). This pre-specified secondary analysis evaluates appropriate therapy and whether ATP reduces the number of appropriate shocks. Methods: The PRAETORIAN trial was an international, investigator-initiated randomized trial, which included patients with an indication for ICD therapy. Patients with prior VTs below 170 bpm or refractory recurrent monomorphic VTs were excluded. In 39 centers, 849 patients were randomized to receive an S-ICD (N=426) or TV-ICD (N=423) and were followed for a median of 49.1 months. ICD programming was mandated by protocol. Appropriate ICD therapy was defined as therapy for ventricular arrhythmias. Arrhythmias were classified as discrete episodes and storm episodes (≥3 episodes within 24 hours). Analyses were performed in the modified intention-to-treat population. Results: In the S-ICD group, 86/426 patients received appropriate therapy, versus 78/423 patients in the TV-ICD group, during a median follow-up of 52 months (48-month Kaplan-Meier estimates 19.4% and 17.5%, P=0.45). In the S-ICD group, 83 patients received at least one shock, versus 57 patients in the TV-ICD group (48-month Kaplan-Meier estimates 19.2% and 11.5%, P=0.02). Patients in the S-ICD group had a total of 254 shocks, compared to 228 shocks in the TV-ICD group (P=0.68). First shock efficacy was 93.8% in the S-ICD group and 91.6% in the TV-ICD group (P=0.40). The first ATP attempt successfully terminated 46% of all monomorphic VTs, but accelerated the arrhythmia in 9.4%. Ten S-ICD patients experienced 13 electrical storms, versus 18 TV-ICD patients with 19 electrical storms. Patients with appropriate therapy had an almost two-fold increased relative risk of electrical storms in the TV-ICD group compared to the S-ICD group (P=0.05). Conclusions: In this trial, no difference was observed in shock efficacy of the S-ICD compared with the TV-ICD. Although patients in the S-ICD group were more likely to receive an ICD shock, the total number of appropriate shocks was not different between the two groups.

Secondary prevention implantable cardioverter-defibrillator (ICD) therapy: value in octogenarians

Background Implantable cardioverter-defibrillator (ICD) therapy is well established for secondary prevention, but studies on the efficacy and safety in elderly patients are still lacking. This retrospective study compared the outcome after ICD implantation between octogenarians and other age groups. Methods Data were obtained from a local ICD registry. Patients who received ICD implantation for secondary prevention at our department were included. All-cause mortality, appropriate ICD therapy and acute adverse events requiring surgical intervention were compared between different age groups. Results 519 patients were enrolled, 34 of whom were aged ≥ 80 years. During the median follow-up of 35 months after ICD implantation 129 patients (annual mortality rate 5.0%) had died, including 16 patients aged ≥ 80 years (annual mortality rate 9.4%). The mortality rate of patients aged ≥ 80 years was significantly higher than that of patients aged ≤ 69 years (p < 0.001), but similar to that of patients aged 70–79 years. Age at the time of ICD implantation was an independent predictor of all-cause mortality (p < 0.001). 29.7% of patients had appropriate ICD therapy with no difference between age groups. Acute adverse events leading to surgical intervention were low (n = 13) and not age-related. Conclusion Age is an independent predictor of mortality after ICD implantation for secondary prevention. Mortality rates did not differ significantly between octogenarians and other elderly aged 70–79 years. Appropriate ICD therapy and acute adverse events leading to surgical intervention were not age-related. Implantable cardioverter-defibrillator therapy for secondary prevention seems to be an effective and safe treatment modality in octogenarians.

IMMU-25. SYNERGY BETWEEN TMZ AND INDIVIDUALIZED MULTIMODAL IMMUNOTHERAPY TO IMPROVE OS OF IDH1 WILD TYPE MGMT PROMOTOR UNMETHYLATED GBM PATIENTS

The prognosis of IDH1 wild type MGMT promotor unmethylated (MGMT-p-UM) GBM patients remains poor. Addition of TMZ to radiotherapy shifted the median OS from 11.8 to 12.6 months (Stupp, Lancet Oncol 2019). We retrospectively analysed the value of individualized multimodal immunotherapy (IMI) to improve OS in these patients. Adults with first event of IDH1wt GBM and documented status of MGMT-p-UM, and treated with IMI in the period June 2015 till July 2020, were selected. IMI consisted of 1/ immunogenic cell death (ICD) therapy (NDV injections + modulated electrohyperthermia), 2/ active specific immunotherapy with autologous mature dendritic cells loaded with tumor lysate or ICD therapy-induced serum-derived antigenic extracellular microvesicles and apoptotic bodies (IO-Vac® is an approved advanced therapy medicinal product since 27/05/2015), 3/ modulatory immunotherapy adapted to the patient, and 4/ complementary medicines. Twenty-eight patients (11f, 17m) had a median age of 48y (range 18-69) and a KPI of 90 (50-100). Extent of resection was complete (11), &lt; complete (9) or not documented (8). Seven patients were treated with surgery/radio(chemo)therapy and subsequent IMI (Group-1); 21 patients were treated with radiochemotherapy followed by maintenance TMZ + ICD therapy, followed by DC vaccines (Group-2). Both groups received further maintenance ICD therapy. Age, KPI and extent of resection were not different amongst both groups. PFS was not assessed because of challenges about pseudoprogression. The median OS of group-1 patients was 11m (2y OS: 0%). Surprisingly the median OS of group-2 patients was 18m with 2y OS of 17% (CI95%: +31, -15), which was significantly (Log-rank: p = 0.027) different from group-1. The data suggest that addition of IMI after local therapy on its own has no relevant effect on OS in IDH1 wild type MGMT-p-UM GBM patients, similar to maintenance TMZ. However, the combination of both TMZ + IMI significantly improves median OS.

Looking for appropriate criterias for SCD prevention: prognostic role of MRI in patients with nonischemic ventricular arrhythmias

Background Currently left ventricular ejection fraction (LVEF) remains the only indicator for identifying candidates for implantable cardioverter-defibrillator (ICD)therapy for the primary prevention of sudden cardiac death (SCD). However the majority of patients suffering SCD have a preserved LVEF and some of them with poor LVEF do not benefit from ICD therapy. Late gadolinium enhancement (LGE) on cardiac-MRI (CMR) has been proposed as an independent predictor of ventricular arrhythmias. Limited data exist on the role and methods of LGE quantification in patients with a nonischemic ventricular arrhythmias. Purpose The goal of this study is to explore whether theextent of LGE would improve risk stratification in patients with a nonischemic ventricular arrhythmias with an indication for implantable cardioverter-defibrillator (ICD) therapy for the primary or secondary prevention of SCD. Methods Fifty six patients with a nonischemic ventricular arrhythmias underwent LGE-CMR prior to ICD implantation for primary and secondary prevention of SCD. LGE extent was quantified using both the full-width half-maximum (FWHM) andthe standard deviation–based (2-SD) method. The primary endpoint was appropriate ICD discharge for sustained ventricular tachyarrhythmia. Results During a median follow-up of 18 [11,5–26,0] months the primary endpoint occurred in 22 patients. The median percentage of LV myocardium fibrosis assessed by the 2-SD method was 9,8 [6,0–18,8]%, while for the FWHM method it was 5,1 [3,0–10,6]% (p&lt;0,001). Intra-observer and inter-observer variability of the FWHM technique was excellent, intraclass correlation coefficients (ICC) 0,97 (95% CI: 0,92–0,99) for intraobserver variability and 0,95 (95% CI: 0,85–0,98) for interobserver variability. The ICC for the 2-SD method were lower: 0,92 (95% CI: 0,76–0,97) and 0,90 (95% CI: 0,69–0,96), for intra- and interobserver variability, respectively. By Cox univariate regression analysis, past syncope, HR: 3,14; (CI: 1,28–7,73), past sustained VT, HR: 8,24; (CI: 2,43–27,96), the presence of LBBB before implantation cardiac resynchronization therapy defibrillator (CRT-D), HR: 0,22; (CI: 0,05–0,96) as well as extent of LGE, HR: 1,067; per 1% increase in the extent of LGE, (CI: 1,029–1,107) demonstrated the strongest association with the appropriate ICD discharge. In multivariate regression analysis, the history of sustained VT, HR: 9,17; (CI: 2,60–32,38; p=0,001) and the value of the extent of LGE, HR: 1,081; per 1% increase in volume of LGE, (CI: 1,034–1,131; p=0,001) demonstrated an independent association with the appropriate ICD discharge. Conclusions FWHM is the optimal semi-automated quantification method in patients with nonischemic ventricular arrhythmias, demonstrating the highest technical consistency. LGE extent is an independent predictor of adverse outcomes in patients with nonischemic ventricular arrhythmia and may have an important role in risk stratification. FUNDunding Acknowledgement Type of funding sources: None. LGE Quantification Event-Free Survival

Secondary prevention implantable cardioverter-defibrillator (ICD) therapy in octogenarians: effective and safe

Aims Implantable cardioverter-defibrillator is well established for secondary prevention, but there is a lack of studies showing efficacy and safety in the elderly. The current study compared the outcome of octogenarians after ICD implantation to other age groups. Methods Data was achieved from a local ICD registry. Patients who received ICD implantation for secondary prevention were included. All-cause mortality, appropriate ICD therapy and acute adverse events requiring surgical intervention were compared between different age groups. Results 519 patients were enrolled. 34 patients were ≥80 years. Over a median follow-up of 35 months after ICD implantation 129 patients (annual mortality rate 5.0%) died, including 16 patients in the age group ≥80 years (annual mortality rate 9.4%). Mortality rate in the age group ≥80 years was significantly higher than in the age groups ≤69 years (p&lt;0.001) but no difference could be seen compared to age groups 70–79 y. Age at the time of ICD implantation was an independent predictor of all-cause mortality (p&lt;0.001). 29.7% of patients had appropriate ICD therapy with no difference between age groups. Acute adverse events leading to surgical intervention were low (n=13) and not age-related. Conclusion Age is an independent predictor of mortality after ICD implantation for secondary prevention. No difference in mortality rate could be seen between octogenarians and other elderly from 70 – 79 years. Appropriate ICD therapy and acute adverse events leading to surgical intervention were not age-related. Implantable cardioverter-defibrillator for secondary prevention seems to be an effective and safe therapy in octogenarians. FUNDunding Acknowledgement Type of funding sources: None.

Subcutaneous ICD combined with VT ablation for the secondary prevention of sudden cardiac death: pilot data from the prospective multinational SICD-VTAbl study

Background The aim of the Subcutaneous ICD Combined with Ventricular Tachycardia Ablation (SICD-VTAbl) Study is to provide preliminary data on the safety and efficacy of a management strategy that incorporates S-ICD implantation and VT ablation among patients with a secondary prevention indication for an ICD. We hypothesize that VT ablation for the prevention of monomorphic VT recurrence combined with S-ICD implantation for termination of life-threatening VT/VF is safe, while reducing the need for device interventions and systemic complications associated with conventional transvenous ICD implantation for secondary prevention. Methods SICD-VTAbl is an uncontrolled, prospective, multinational observational study, conducted in France, Germany, US (Rochester NY, and Rochester MN) and coordinated in Israel. We aim to prospectively enroll 30 patients presenting with scar-related VT/VF who will undergo VT ablation/substrate modification followed by S-ICD implantation. The primary endpoint is the first occurrence of S-ICD therapy (appropriate and inappropriate). Secondary endpoints include separate occurrence of appropriate and inappropriate ICD therapies, peri-procedural complications, and adverse clinical outcomes. Results We provide clinical, arrhythmia, and outcome data on the first 15 patients enrolled in the SICD-VTAbl Study through February 2021. Mean age was 59±12 years, 78% were males, 60% had New York Heart Association (NYHA) Class ≥II symptoms, 20% had renal insufficiency, and 33% were treated with an antiarrhythmic medication (all amiodarone). Periprocedural, arrhythmia, and long-term outcome data are provided in Table 1. There were no major complications associated with the VT ablation and the S-ICD implantation procedures. During a median follow-up of 6 months (interquartile range: 2–12 months), 2 patients (13%) received S-ICD therapy: one patient (7%) experienced VF terminated by the S-ICD and one patient experienced a single episode of inappropriate S-ICD therapy. Adverse events during follow-up, unrelated to study procedures, occurred in 3 patients (20%): hospitalization for heart failure exacerbation (N=1) and non-cardiovascular hospitalizations (N=2). None of the patients died during follow-up (Table 1). Conclusions Our preliminary data from the SICD-VTAbl Study suggest that a management approach that incorporates VT ablation followed by S-ICD implantation is safe and may lead to improved arrhythmia and clinical outcomes in patients presenting with a secondary prevention indication for an ICD. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): Research grant to Sheba Medical Center from Boston Scientific

Long-term outcomes among a cohort of 4296 implantable cardioverter-defibrillator patients: insights from the UMBRELLA study

Background Large observational real-world studies describing modern implantable cardioverter-defibrillator (ICD) populations with long-term follow-up are lacking. Purpose To assess the incidence of arrhythmias in a cohort of contemporary patients undergoing ICD implant from 2005 and 2017 and to analyze the arrhythmic risk and mortality according to their clinical profiles. Methods UMBRELLA (NTC01561144) is a prospective, multicentre, nationwide study of ICD patients followed by remote monitoring. All device information was automatically stored through the remote monitoring system and a blinded review of all the stored arrhythmic episodes was performed. The study outcomes were first appropriate ICD therapy and all-cause death. Results The study population consisted of 4296 patients (61.9±12.9 years, ischaemic cardiomyopathy (ICM): n=2150, dilated cardiomyopathy (DCM): n=1166, valvular heart disease (VHD): n=119, hypertrophic cardiomyopathy (HCM): n=294, arrhythmogenic right ventricular cardiomyopathy (ARVC): n=71, Brugada syndrome (BS): n=143, long QT syndrome (LQTS): n=43, and adult congenital heart disease (ACHD): n=60)). Primary prevention (PP) was the main indication (n=2758). During a mean follow-up of 46.6±27.3 months, 16,067 episodes of sustained ventricular arrhythmia (SVA) occurred in 1344 patients. Appropriate ICD therapy was delivered to 85.7% (n=13,767) episodes of SVA in 1173 patients (27.3% of population). A higher risk of first appropriate ICD therapy was observed in VHD (HR: 1.94, 95% CI: 1.43–2.62), ARVC (HR: 1.84, 95% CI: 1.28–2.66), ICM (HR: 1.51, 95% CI: 1.29–1.78), and DCM (HR: 1.28, 95% CI: 1.07–1.53) whereas patients with HCM (HR: 0.72, 95% CI: 0.54–0.96) and BS (HR: 0.25, 95% CI: 0.14–0.45) were at significantly lower risk (Figure 1A). In multivariate analysis (Table 1), age, gender, atrial fibrillation (AF), secondary prevention, LVEF ≤35%, and QRS width emerged as clinical predictors of appropriate ICD therapy, whereas CRT-D correlated with lower risk. An independently higher risk was found in DCM, VHD, and ARVC, and a lower risk in BS patients. At follow-up, 590 deaths (13.4% of population) were reported. Patients with ICM (HR 3.90, 95% CI: 2.58–5.90), DCM (HR 3.33, CI 95%: 2.18–5.10), and VHD (HR 3.97, CI 95%: 2.25–6.99) had worse prognoses and it was significantly better in BS patients (HR 0.11, 95% CI: 0.01–0.67, p=0.017) (Figure 1B). In multivariate analysis, age, gender, AF, renal failure, diabetes and reduced LVEF, emerged as independent predictors of all-cause death (Table 1). Conclusions Irrespective of the aetiology, contemporary ICD patients with an arrhythmic substrate derived from left ventricular systolic dysfunction had a similar risk of ICD life-saving interventions and death. FUNDunding Acknowledgement Type of funding sources: None. Table 1 Figure 1