Prophylactic ICD Research Articles

Periodic Repolarization Dynamics (PRD) identifies patients who profit from ICD implantation, A meta-analysis of the predictive value of PRD

Abstract Background Periodic repolarization dynamics (PRD) is an electrocardiographic marker that quantifies sympathetic-activity associated instabilities of cardiac repolarization. PRD is a strong predictor of mortality in patients with ischemic (ICM) and non-ischemic cardiomyopathy (NICM) and has been proposed to identify patients who benefit from prophylactic ICD implantation. Purpose To conduct a systematic review and meta-analysis concerning the prognostic value of PRD for predicting all-cause mortality in relation to prophylactic ICD-implantation. Methods This meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A total of 25 articles were screened and 7 randomized and non-randomized controlled trials identified. Finally, a total of 5 could be included in the analysis (Fig.1). Patients were stratified into patients with or without prophylactic ICD-implantation (Fig.2). The prognostic value of PRD for predicting all-cause mortality was extracted from published data as hazard ratio (HR) per 1 deg2 increase in PRD. We used inverse-variance-weighted average meta-analysis to calculate fixed and random effect models to estimate the overall predictive value of PRD in both groups. The interaction between PRD and prophylactic ICD-implantation for predicting mortality was calculated using meta-regression analysis. All analyses were performed using CRAN R v. 4.1.2 and the meta-package v 5.2.0. Results We included 4,338 patients in this meta-analysis, of whom 3,167 (73%) suffered from ICM and 1,171 (27%) from NICM. 1,906 (44%) patients were treated with an ICD. During an estimated mean follow-up time of 3.2 years, 604 (14%) patients died. Fig. 2 (left) shows patients without ICD treatment (N = 2,432, 56%). In these patients, a 1 deg2 increase in PRD was significantly associated with an overall 8% increase in mortality (fixed effect HR 1.08; 95% CI 1.06-1.10; p< 0.001, random effect HR 1.08; 95% CI 1.06-1.11; p < 0.001). Fig. 2 (right) displays the prognostic value of PRD in patients treated by ICD (N = 1,906). In these patients, a 1 deg2 increase in PRD was significantly associated with an overall 3% increase in mortality (fixed-effect HR 1.03; 95% CI 1.01-1.05; p< 0.001, random-effect HR 1.03; 95% CI 1.00-1.06; p < 0.001). An increase in PRD was not significantly associated with an increase in mortality in patients from the EU-CERT-ICD and DANISH trial. There was a significant interaction between PRD and prophylactic ICD-implantation for predicting all-cause mortality (p = 0.008). Conclusion In patients with ICM and NICM, PRD is a strong predictor of all-cause mortality in patients with and without prophylactic ICD. The significant interaction between PRD and prophylactic ICD-implantation most probably implies a reduction in the risk identified by PRD through ICD implantation. Consequently, PRD could prove a useful tool for identifying patients that might benefit from ICD treatment.Figure 1Figure 2

Cardiac magnetic resonance for prophylactic implantable-cardioverter defibrillator therapy international registry: prognostic value of LGE distribution in non-ischemic dilated cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by Italian Ministry of Health, Rome, Italy (RC 2017 R659/17-CCM698). Background/Introduction Tissue characterization obtained by cardiac magnetic resonance (CMR) has emerged as a promising tool for better identification of non ischemic cardiomyopathy patients at high arrhythmic risk and thus worthy of prophylactic ICD therapy. Purpose Current analysis has the scope to assess the prognostic value of fibrosis, as evaluated by late gadolinium enhancement sequences (LGE) specifically regarding its LV wall distribution, and a CMR-derived risk score. The primary endpoint was all-cause mortality. The secondary end-point consisted of major adverse arrhythmic cardiac events (MAACE), defined as combination of SCD, aborted SCD, and sustained ventricular tachycardia Methods DERIVATE Study is an international, multicenter, prospective, observational registry including consecutive patients from 21 sites referred for heart failure (HF) work-up including transthoracic echocardiography (TTE) and CMR without a history of previous major ventricular arrhythmias. Inclusion criteria were: (i) aged 18 or older, (ii) chronic HF, and (iii) LV-EF<50% at initial TTE. All patients underwent TTE and CMR within 3 months. Patients with (i) decompensated within 3 months of enrollment, (ii) recent myocardial infarction (<40 days), (iii) unstable angina, (iv) severe valvular disease, (v) primary or secondary cardiomyopathies other than NICM, (vi) cardiac amyloidosis, and (vii) congenital heart disease were excluded. Results The entire cohort consisted of 1384 subjects [mean age: 56±14 years, male: 948 (68.4%)]. The median follow-up time was 959 days. Mortality and MAACE occurred in 92 (6.6%) and 125 (9%) patients, respectively. SCD, aborted SCD, and sustained VT occurred in 15 (1.1%), 80 (5.8%), and 104 (7.5%), respectively. The sum of events exceeds the overall number of MAACE because several events could occur in the same patients but just the first event was counted. In the multivariate analyses for all-cause mortality, only the number of segments with LGE at the level of the septum was an independent predictor (p = 0.002), while in the analyses for MAACE the only independent predictors were male gender, LVEDVi by CMR, and the number of segments with LGE at the level of septum inferior. Based on the multivariate analysis, the DERIVATE score (including all 1384 patients) ranging from 0 to 8 (Cox regression analysis HR=1.35, 95%CI 1.24–1.46, p< 0.001) was realized. The redistribution of patients according to the CMR composite DERIVATE risk/year MAACE was of 44%, 37% and 32% for the low, intermediate and high risk groups, respectively. Conclusions The arrhythmic risk of patients with NICM is also dependent on the different distribution of fibrosis in the LV. The redistribution of the event rate according to the CMR composite risk score indicates the potential to alter the decision on ICD implantation in a relevant portion of NICM patients. These results warrant further confirmation in prospective randomized controlled trials.

Incidence of ventricular tachyarrhythmias and clinical outcomes in primary prophylactic ICD patients in relation to localization of myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Introduction According to current guidelines, primary prophylactic ICD implantation is indicated with a class IA recommendation in patients with severely reduced EF < 35% and ischaemic heart disease. However, it is unclear whether there are differences in patient outcomes related to the localization of myocardial infarction. Aim of the study was to compare the incidence of ventricular tachyarrhythmias and clinical outcomes in primary prophylactic ICD-patients with ischaemic heart disease in relation to the localization of myocardial infarction. Methods A total of 448 consecutive ICD patients from a prospective single-centre ICD-registry who underwent primary prophylactic ICD implantation due to ischaemic cardiomyopathy between 1996 and 2021 were analyzed. Patients with previous anterior wall myocardial infarction (AWMI, n = 293) were compared to those with posterior wall myocardial infarction (PWMI, n = 155). Patients with both AWMI and PWMI were excluded. The median follow-up time was 6 years in both groups. Results Patients with AMWI were younger, more often female, and less often received cardiac synchronization therapy (Table 1). Patients with previous PWMI more often had ICD therapy during follow-up (Figure 1) due to the higher incidence of ventricular tachycardias (Table 1). The all-cause mortality rate was similar between both groups. Conclusion Primary prophylactic ICD patients with previous PWMI have a 10% higher incidence of ventricular tachycardias after 6-year follow-up than ICD patients with previous AMWI. This might be explained by the proximity of the inferior infarction to the mitral isthmus and should be considered when ablating VTs in patients with PWMI.

Electroanatomic mapping system guided His bundle pacemaker implantation: experience of the His bundle registry graz

Abstract Funding Acknowledgements Type of funding sources: None. Background Electric conduction disturbances are very common, however, patients in need for ventricular pacing may suffer from pacing-induced heart failure due to unphysiological pacing by the right ventricular lead. Conducting system pacing allows to overcome this common issue with a more physiologic approach, but real-life procedural data using this technology is scarce. Methods We report a single centre experience of the first 63 consecutive patients being implanted with a His-bundle-based pacemaker 09/2020-11/2022 per 3D-mapping guided implantation due to bradyarrhythmia, or for cardiac resynchronisation therapy in heart failure combined with a left-ventricular lead (HOT-CRT) ± a right ventricular defibrillator lead. The identification of the His-bundle-location was done with a 3D electroanatomic mapping system via an introducing sheath that is provided with electrodes at its tip. Results Mean age was 71 [18;87] years, 18/63 (29%) patients were female, mean baseline LVEF was 46±15%. Baseline ECG was captured before implantation: QRS width was 127±34ms, with typical LBBB in 19/63 (30%), typical RBBB in 5/63 (8%), alternating BBB in two patient (3%) and either no BBB or ventricular escape rhythm in 37/63 (59%). Indications for implantation were AV-block grade II-III in 31/63 (49%), primary prophylactic ICD indication in HFrEF in 18/63 (29%), atrial fibrillation with bradycardic conduction in 8/63 patients (13%), sick-sinus-syndrome in 4/63 (7%) and secondary prophylactic ICD indication in one patient (2%). In 57/63 (90,5%) a primary device was implanted, in 6/63 (9,5%) a pre-existent device was upgraded with a HB lead. Therefore, 23 dual-chamber-pacemaker, 5 single-chamber-pacemaker, 10 single-chamber CRT-P, 17 dual-chamber CRT-P, 4 single-chamber CRT-D, 4 dual-chamber CRT-D were implanted. In 63 patients his bundle pacing was attempted, while in 6/63 (9%) patients outside of this analysis the attempt was not successful, these patients were consecutively implanted with a non-HBP-device and therefor excluded from the further analysis. In the 63 patients included in this analysis with a primary successful pacing at the his-position, 5/63 (8%) his-bundle-leads dislocated within the first 48 hours, leading to a secondary success rate of 92%. There were two post-procedural pneumothorax that needed drainage, no major procedure-related complications occurred. Median skin-to skin procedure time was 111±47 minutes in his-bundle-device-implantation. The paced QRS width at the post-implantation follow up was 113±27ms with a change in QRS width of -15±39ms (+72; -92ms). The mean his-bundle sensing was 5,38±5,6mV and the mean threshold 1,1±0,86V over 1,0±0,5ms (0,4;1,5ms). The proportion of ventricular pacing was 75±36%. Conclusion Electroanatomic-guided His bundle pacing as a new innovative technic for physiological pacing is viable including high implantation success rate as well as electric impact, both regarding QRS width and pacing threshold.

Evaluation of MADIT II risk stratification score among registry of heart failure patients with primary prevention ICD/CRTD device

Abstract Funding Acknowledgements Type of funding sources: None. Background Current guidelines advocate primary prevention ICD implantation for all symptomatic heart failure (HF) patients with low LVEF. As most patients will not use their device during lifetime, a score delineating subgroups with differential ICD benefit is crucial. The MADIT Risk Stratification Score (MRSS) based on 5 parameters including: age>70, Creatinine >1.4 mg/dl, QRS width >120ms, presence of AF, and NYHA >2, was developed for this purpose. Objective Evaluate MRSS among Israeli nationwide registry of HF patients implanted with prophylactic ICD/CRTD. Endpoints included overall mortality, sustained ventricular arrhythmia (VA), and competing risk of arrhythmic (VA-related) versus non-arrhythmic death, a surrogate for potential ICD survival benefit. Methods Study based on comprehensive registry of ICD/CRTDs implanted in Israel between 2011-2018. All registry patients were categorized into MRSS-based risk-groups (low-risk- MRSS 0, intermediate-risk- MRSS 1-5, very high-risk (VHR) group defined by Creatinine >2.5mg/dL). Univariate and Kaplan Meier analysis used to evaluate the association of risk groups with study endpoints. Results 2177 HF patients, implanted with a primary prevention ICD (1255, 58%) or CRTD (922, 42%) were included. There were 189 (8.7%) patients with sustained VA and 316 (14.5%) deaths during median follow-up (F/U) period of 2.5 years. A significant correlation was found between MRSS-based risk subgroups and overall mortality (p 0.001). However, MRSS association with sustained VA was weak (p 0.2). Notably, the MRSS-based very high-risk (VHR) subgroup had an exceptionally high mortality but low VA incidence. Competing risk of arrhythmic versus non-arrhythmic death revealed a large and significant ICD survival benefit among the low and intermediate MRSS-based risk subgroups, with 10.2 and 12.3 months survival gained over 3-year F/U period among these subgroups, respectively (p 0.001). The VHR subgroup in contrast, showed a minimal non-significant ICD survival benefit. Conclusions Use of MRSS among a contemporary real-world registry of HF patients revealed subgroups with differing ICD survival benefit, suggesting it as a universal tool to predict ICD survival benefit. MRSS-based VHR subgroup may not gain survival benefit from prophylactic ICD implant.

Value of programmed electrical stimulation in Brugada Syndrome: a cohort study

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Prognostic value of programmed electrical stimulation (PES) in Brugada Syndrome (BrS) remains controversial. Substantial controversy exists regarding usefulness of PES in identifying BrS patients at risk of sudden cardiac death (SCD). Implantation of an implantable cardioverter-defibrillator is the only reliable form of SCD prevention in this specific population Purpose To determine if induction of sustained ventricular arrhythmia (VA) in PES is a predictor of cardiac events (CE), defined as the composite of SCD, appropriate ICD therapy for VA or unexplained syncope. Methods A retrospective analysis of 34 patients with spontaneous or pharmacologically induced type 1 Brugada pattern, submitted to electrophysiology study with PES between 2015 and 2019 in a Portuguese Center, was performed. Patients were followed for 24 months. Hospital records and monitoring data from cardiac devices were consulted. The Mann-Whitney U test was used for median comparison between groups. Binary logistic regression through the stepwise method was performed to evaluate categorical features. Results 35% (n=12) and 27% (n=9) had spontaneous type 1 and type 2 Brugada pattern in basal electrocardiography, respectively. 23% (n=8) had VA induced by PES. The mean age was 51,2±12,3 years. 71% (n=24) were male. 15% (n=5) had history of cardiac syncope, and 27% (n=9) had a family history of SCD. 9% (n=3) were carriers of a SNC5A mutation. Mean AH time and HV time were, respectively, 105±31,9, and 49±8,5ms. During the 24 months of follow-up, 9% (n=3) suffered a CE (2 unexplained syncope and 1 SCD). None of the patients who suffered CE had VA inducible at PES study. There was no statistical significance in the occurrence of cardiac events when comparing both groups (VA induced in PES vs. no induced arrhythmia) (p=0,49, OR 0,89, IC 95% 0,70;1,02). Through binary logistics, adjusted for potential confounders (gender, history of syncope, history of family SCD and identification of a genetic variant), patients with spontaneous type 1 Brugada pattern in basal electrocardiography were 2,2 times more likely to have a CE (IC 95% 0,12;40,2). Conclusion In this population, VA induced by PES was not a predictor of CE during the follow-up period, which highlights the difficulty of risk stratification in patients with BrS. New risk-stratification tools are urgently needed to select those patients at higher-risk of SCD, which are candidates for prophylactic ICD implantation.

MP-453092-9 PROGNOSTIC SIGNIFICANCE OF SUSTAINED VENTRICULAR ARRHYTHMIAS OCCURRING UNDER WEARABLE CARDIOVERTER DEFIBRILLATOR PROTECTION IN POST-INFARCT PATIENTS WITH A LEFT VENTRICULAR DYSFUNCTION

Although the first few months after acute myocardial infarction (MI) are associated with an increased risk of SCD, in particular when LVEF is ≤0.35, prophylactic ICDs are not recommended until LVEF has been reassessed after a period of 40 to 90 days following an acute MI. During this ‘waiting period’, wearable cardioverter defibrillators (WCD) may be used in patients considered at high-risk of SCD, but the prognostic significance of sustained VT/VF occurring under WCD protection is unknown. We sought to evaluate whether the occurrence of VT/VF, successfully treated by a WCD in the early post-MI phase, is associated with a poorer outcome with regard to death or VT/VF recurrences at one year. We recruited a series of patients with an acute MI and a resulting LVEF≤0.35 (evaluated 2-5 days after admission) who were prescribed a WCD upon hospital discharge (for a maximal expected duration of 3 months) and who were subsequently implanted with an ICD either because sustained VT/VF occurred while on WCD (Group A) or because LVEF remained ≤0.35 after the post-MI ‘waiting period’ (Group B). Informed consent was mandatory to participate in the study. Adjudication of arrhythmic events was based on the analysis of ICD/WCD recordings. Based on previous publications, eleven relevant clinical parameters (associated with a higher risk of SCD after MI) were assessed for statistical analysis in addition to the occurrence of VT/VF while on WCD. The study population consisted of 1032 consecutive patients (Group A: n=72, Group B: n=960) from 41 French centers. The median follow-up after ICD implantation was 2.6 years [interquartile range=1.5-3.9]. The clinical characteristics of the patients are shown in Table 1. At one year: 1) VT/VF requiring ICD treatment occurred in 22.2% vs 3.5% (p<0.0001) respectively in Group A and Group B patients and 2) death from any cause occurred in 11.1% vs 3.4% (p=0.001) respectively in Group A and Group B patients (Figure 1). Occurrence of VT/VF while on WCD was independently associated with the occurrence of VT/VF and all-cause death after ICD implantation. Our study suggests that the occurrence of VT/VF, while on WCD in the early post-MI period after an acute MI, is an independent marker of a poorer one-year prognosis in patients with a LVEF≤0.35. Further studies are needed to assess which therapeutic strategies might improve the short-term prognosis in these patients.Tabled 1Table 1: Patient characteristicsVariablesGroup A (n = 72)Group B (n = 960)p-valueGender (male, %)88.9%82.9 %0.25Age at ICD implantation (years, mean ± SD)61.5 ± 9.060.7 ± 10.50.52Current smoker (%)50.7 %47.9 %0.90Diabetes mellitus (%)30.6 %23.2 %0.20History of hypertension (%)47.9 %41.7 %0.32History of atrial fibrillation (%)8.3 %4.8 %0.17History of previous myocardial infarction (%)16.7 %18.8 %0.75Early (<24 hours) coronary revascularization for the index myocardial infarction (%)51.4 %66.3 %0.014Average heart rate during WCD (bpm, mean ± SD)73.2 ± 12.568.3 ± 9.6<0.0001NYHA III/IV class at ICD implantation (%)39.6%19.1%0.001Serum creatinine at ICD implantation [mg/L, median (Q1 - Q3)]10.8 (9.2 - 13.1)10.7 (8.9 - 13.2)0.42LVEF at ICD implantation (%, mean ± SD)29.1 ± 6.629.3 ± 6.20.78 Open table in a new tab

449 HYPERTROPHIC CARDIOMYOPATHY: A CASE OF CHALLENGING ARRHYTHMIC RISK STRATIFICATION

Abstract Hypertrophic cardiomyopathy (HCM) is a common disease, mostly inherited, with a prevalence of 1:500. Cornerstone of the clinical management of HCM patients is stratifying the risk of sudden cardiac death (SCD) which is the most frightening complication despite its relatively low incidence (0,9% per year). Although mathematical risk scores, as proposed by ESC, are the most used to assess the probability of arrhythmic complications leading to SCD, they have been associated with low sensitivity, precluding some high-risk patients from prophylactic ICD implantation. Among the tools at clinicians’ disposal for risk stratification in HCM patients, the latest AHA/ACC guidelines propose an “individual risk markers strategy”, based on the presence of ≥1 clinical feature such as a family history of SCD, extreme left ventricular hypertrophy (LVH), unexplained recent syncope, NSVT, late gadolinium enhancement (LGE) at CMR, systolic dysfunction and LV apical aneurysm. We present a case that lets us reflect on arrhythmic risk stratification. P.C. is a 58 y.o. male with a history of septal hypertrophy (19 mm) and T wave inversion but without an established diagnosis of HCM. He did not have any familiar history of syncope or SCD. He came to the emergency department for epistaxis and was admitted to the cardiology unit due to the previously mentioned findings, where he underwent cardiac-CTA and CMR showing myocardial bridge of left anterior descending artery, LVH with apical aneurysm and LGE areas localized on the apex (transmural) and on the interventricular septum (subendocardial). No signs of dynamic LVOT obstruction or atrial enlargement emerged from echocardiography. During the observation, asymptomatic NSVT were recorded on continuous ECG monitoring. According to the ESC risk prediction score (3.7%) ICD was not strictly indicated but considering the CMR high-risk profile (according to the suggestions of AHA/ACC) we proposed an ICD implantation anyways. The patient refused any invasive procedure and was implanted with a loop recorder. At 12 months remote monitoring showed a single episode of self-terminated sustained polymorphic ventricular tachycardia (02:23 mm: ss) symptomatic of pre-syncope. The patient was then immediately reached and admitted for ICD implantation in secondary prevention. According to the patient's will, and the no need for bradycardia therapy, an S-ICD was implanted. Figure 1LV apical aneurysm at CMRFigure 2Remote Monitoring

Electroanatomic mapping system guided his bundle pacemaker implantation: experience of the his bundle registry graz

Abstract Funding Acknowledgements Type of funding sources: None. Background Patients with bradyarrhythmia in need for ventricular pacing may suffer from pacing-induced heart failure due to unphysiological right ventricular pacing. His bundle pacing (HBP) allows to overcome this common issue with a more physiologic approach but real-life procedural data using this technology is scarce. Methods We report a single centre experience of the first 44 consecutive patients being implanted with a His-bundle-based pacemaker 09/2020-11/2021 per 3D-mapping guided implantation due to different types of bradyarrhythmia, or for cardiac resynchronisation therapy in heart failure combined with a left-ventricular lead (HOT-CRT) ± a right ventricular defibrillator lead. The positioning of the His-bundle-lead was done by identifying the His-bundle-location with a 3D electroanatomic mapping system via an introducing sheath that is provided with electrodes at its tip. Results Mean age was 70 [16;86] years, 12/44 (27%) patients were female, mean baseline LVEF was 44±18%. Baseline ECG was captured: QRS width was 123±33ms, with typical LBBB in 14/44 (32%), typical RBBB in 4/44 (9%), alternating BBB in one patient (2%) and either no BBB or ventricular escape rhythm in 25/44 (57%). Indications for implantation were AV-block grade II-III in 19/44 (43%), primary prophylactic ICD indication in HFrEF in 13/44 (30%), atrial fibrillation with bradycardic conduction in 7/44 patients (16%), sick-sinus-syndrome in 4/44 (9%) and secondary prophylactic ICD indication in one patient (2%). In 41/44 (93%) a primary device was implanted, in 3/44 (7%) a pre-existent device was upgraded with a HB lead. Therefore, 14 dual-chamber-pacemaker, 5 single-chamber-pacemaker, 8 single-chamber CRT-P, 11 dual-chamber CRT-P, 4 single-chamber CRT-D, 2 dual-chamber CRT-D were implanted. In 50 patients HBP was attempted, while in 6/50 (12%) patients outside of this analysis the attempt was not successful, these patients were consecutively implanted with a non-HBP-device and therefor excluded from the further analysis. In the 44 patients included in this analysis with primary successful HBP, 4/44 (9%) his-bundle-leads dislocated within the first 48 hours, leading to a secondary success rate of 91%. There were two post-procedural pneumothorax that needed drainage, no major procedure-related complications occurred. Median skin-to skin procedure time was 109±50 minutes. The paced QRS width at the post-implantation follow up was 115±32ms with a change in QRS width of -10ms (+72;-92ms). When excluding the secondary lead dislocations and including only the successful HB paced QRS complexes, the paced QRS width was 105±30ms and the change in QRS width was -12±42ms. The mean his-bundle threshold was 1,2±1V over 0,5ms (0,5;1,5ms). The proportion of ventricular pacing was 69±38%. Conclusion Electroanatomic-guided His bundle pacing is feasible, with high implantation success rate and electric impact, both regarding QRS width and pacing threshold.

Reduced longitudinal strain in the left ventricular inferior wall predicts malignant arrhythmia in non-ischemic heart failure. A DANISH substudy

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND Small studies have suggested that poor regional myocardial function may be associated with malignant arrhythmias, in particular around the inferior-posterior region. We tested this hypothesis in a subgroup of patients from the DANISH trial. METHODS From two centers, 317 patients with non-ischemic heart failure (LVEF &amp;lt; 35%) from the DANISH trial were evaluated by 2D-strain echocardiography. Regional strain was calculated as the average longitudinal strain in basal-, midventricular- and apical segments in each of the six left ventricular walls. Reduced regional function was defined as below-median regional strain. The endpoint was a composite of sudden cardiac death (SCD), sustained VT, admission with ventricular arrhythmia, and appropriate therapy from a primary prophylactic ICD. Time-to-first-event analysis was performed using Cox models. RESULTS Mean age at inclusion was 62 years (72% male), median LVEF was 25% (IQR 20-30) median inferior strain was -8.7% (IQR -12.3; -4.9). After a five-year follow-up, 43 events were observed. Reduced inferior strain was associated with the composite endpoint in univariate analysis with a HR 2.08(95% CI 1.11-3.90), P = 0.021. After multivariate adjustment for clinical and echocardiographic parameters, inferior strain remained an independent predictor with a HR 2.78(95% CI 1.39–5.56), P = 0.004. Strain measurements in no other region were associated with the endpoint in the multivariate analysis. In subgroup analysis of patients in the two lower age tertiles (&amp;lt;68 of age) we found that reduced inferior- and posterior strain were associated with development of the composite endpoint after multivariate adjustment with HRs of 3.25(95% CI 1.41-7.53), P = 0.006 and 2.51(95% CI 1.14-5.53), P = 0.022. CONCLUSIONS Low inferior-posterior strain was associated with a 2-3-fold increase in risk of malignant arrhythmia and SCD in patients with non-ischemic heart failure. Abstract Figure.

Abstract 9202: Sudden Cardiac Death and Icd Use in Rasopathy-Associated Hypertrophic Cardiomyopathy: An International Multi-Centre Study

Introduction: Sudden cardiac death (SCD) burden in RASopathy patients (pts) with hypertrophic cardiomyopathy (RAS-HCM) is not known. We compared SCD events and transplant-free survival in RAS versus primary HCM (P-HCM) pts. Methods: The international 22-center retrospective cohort study (PRIMaCY) included 190 pediatric RAS-HCM and 568 P-HCM pts. The primary outcome was 10-year freedom from SCD events (composite of SCD, resuscitated sudden cardiac arrest, and appropriate shock from a prophylactic ICD), estimated using Kaplan Meier method. Results: Of 190 RAS-HCM pts, 82% had Noonan syndrome. Age at diagnosis was lower in RAS-HCM vs P-HCM (0.9 vs 9.7 yrs, p&lt;0.001). There was no difference in baseline LV posterior wall or septal thickness, but LVOT gradient was higher in RAS-HCM vs P-HCM (30 vs 13mmHg, p&lt;0.001). However, frequency of myectomy was not different in RAS-HCM vs P-HCM (15.2% vs 16.7%, p=0.55). Eighteen RAS-HCM pts died (4 SCD, 2 bradycardic arrests, 5 heart failure, 3 respiratory failure, 2 other) with lower 10-year transplant-free survival in RAS-HCM vs P-HCM (84.2% vs 91.6%, p=0.026). Although 10-year cumulative proportion of SCD events was lower in RAS-HCM than P-HCM (5.4% vs 15.1% respectively, p&lt;0.001) (Figure 1), the median age at event was not different (12yrs in RAS-HCM vs 15.2yrs in P-HCM). Of 5 RAS-HCM pts with a SCD event, 4 died and 1 received a secondary prevention ICD. An additional 10 pts received a prophylactic ICD with no appropriate shock during follow-up. The 10-year cumulative proportion of prophylactic ICD was lower at 6.3% in RAS-HCM vs 27.2% in P-HCM (p&lt;0.001). Conclusion: Transplant-free survival was lower in RAS-HCM than P-HCM with mortality related primarily to non-SCD events. Of the RAS-HCM patients with SCD events, 4 died without an ICD highlighting the need for better risk prediction models for both SCD and heart failure mortality in this population.

Abstract 10353: Independent Validation of the Ecg Risk Score for Sudden Death Risk Stratification in Pediatric Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is the leading cause of sudden cardiac death (SCD) in children and young adults. An ECG risk score tested in a Swedish cohort of 155 children with HCM had 97% sensitivity, 80% specificity, 45% positive predictive value (PPV), and 99% negative predictive value (NPV) for SCD risk prediction. Our goal was to validate the ECG risk score in an independent HCM cohort. Methods: Phenotype-positive pediatric HCM patients seen at a single center between 1987-2019 with at least 5 years follow-up from diagnosis, or a SCD event within 5 years of diagnosis, were retrospectively identified. First-evaluation ECGs were analyzed by a single operator blinded to patient outcomes. ECG risk score was calculated using QRS electrical axis, amplitude, duration, ST/T-wave abnormalities and QTc duration. The primary outcome was a composite of SCD, aborted sudden cardiac arrest, and appropriate shock from a prophylactic ICD. Results: Of 144 eligible patients with a median follow-up 14.6 yrs, 22 experienced SCD events within five years from diagnosis at a median age 12.1 yrs. The ECG risk score in patients experiencing a SCD event was 2-fold higher i.e. 8 (IQR 7-10) compared to the remaining cohort i.e. 4 (IQR 2-8) (p&lt;0.001). An ECG risk score &gt;5 had a sensitivity of 95% (CI 77%-100%), specificity 56% (46%-65%), PPV 28% (24%-33%), NPV 99% (91%-100%), and a receiver operating characteristic area under the curve of 0.76 for its ability to discriminate between patients with and without SCD events ( Figure 1 ). Compared to the discovery cohort, the score had strong sensitivity and NPV, but lower specificity and PPV. Conclusions: The ECG risk score for SCD risk stratification performed well in an independent Canadian validation cohort but overestimated SCD risk. Futher analysis will determine if inclusion of the ECG risk score can enhance the performance of currently available SCD risk prediction models for pediatric HCM.

The DAPA Trial in the Context of Previous Prophylactic ICD Landmark Trials.

In patients with ischaemic cardiomyopathy and severely reduced left ventricular ejection fraction (LVEF), an arrhythmogenic milieu is created by a complex interplay between myocardial scarring (assessed by cardiac MRI) and multiple other factors (ventricular ectopy, ischaemia and autonomic imbalance), favouring the occurrence of arrhythmic sudden cardiac death (SCD). Currently, a dynamic and robust model of dichotomised SCD risk assessment after primary percutaneous coronary intervention (PCI) is lacking, underlining the urgent need for further refinement of the widely accepted and guidelines-based criteria (ischaemic cardiomyopathy, LVEF ≤35%) for primary prevention. This review addresses the potential additional value of the recently published Defibrillator After Primary Angioplasty (DAPA) trial results. The DAPA trial conveys important messages and provides novel perspectives regarding left ventricular function post-primary PCI as an (early) risk marker for SCD and the impact of prophylactic ICD implantation on survival in this cohort. In the context of other previous primary prevention trials, DAPA was the first trial including only ST-elevation MI patients all treated with acute PCI.

B-PO03-162 MICROVOLT QRS ALTERNANS WITHOUT MICROVOLT T WAVE ALTERNANS IN HYPERTROPHIC CARDIOMYOPATHY: A NOVEL RISK MARKER OF LATE VENTRICULAR ARRHYTHMIAS

T wave alternans (TWA) is associated with ventricular arrhythmia (VA) but QRS alternans (QRSA) has not been characterized in hypertrophic cardiomyopathy (HCM). To assess microvolt QRSA/TWA in relation to traditional risk factors (RF) and late VA outcomes in HCM. Prospectively enrolled HCM patients (n=130, age 53±14yrs) with prophylactic ICD had digital 12-lead ECGs recorded during ventricular pacing at 100-120bpm. QRSA/TWA was quantified by the spectral method. Patients were categorized as QRSA+ and/or TWA+ based on ≥2 precordial leads having an alternans signal:noise >3 in ≥3 consecutive 128-beat segments. The VA endpoint was appropriate ICD therapy. QRSA+ and TWA+ occurred together in 28% and alone in 7% and 7% of patients, respectively. QRSA and TWA magnitude (1.9±0.6 vs 6.2±2.0μV, p<0.01; 1.3±0.3 vs 3.0±0.7μV, p=0.01) increased with pacing rate. LV thickness was greater in QRSA+ than QRSA- patients (22±7 vs 20±6mm, p=0.04). At 5 years follow up, 17% of patients had VA. QRSA+ patients had more VA than QRSA-, with QRSA+/TWA- patients having the highest VA rate (Figure). In patients with <2 RF, the annual VA rate was only 0.6% in QRSA- patients. Separate multivariable Cox models revealed QRSA+ (HR[95%CI]: 2.9[1.2-7.0], p=0.02) and QRSA+/TWA- (7.9[2.9-21.7], p<0.01) as the most significant predictors of VA. TWA and traditional RF did not predict VA. In HCM, microvolt QRSA is a novel rate-dependent phenomenon that can exist without TWA and is associated with greater LV thickness. QRSA in the absence of TWA increases VA risk 8-fold in all patients, while the absence of QRSA confers low VA risk in patients with <2 RF, which may inform ICD therapy.

A novel risk model for predicting potentially life-threatening arrhythmias in non-ischemic dilated cardiomyopathy (DCM-SVA risk)

BackgroundNon-ischemic dilated cardiomyopathy (DCM) can be complicated by sustained ventricular arrhythmias (SVA) and sudden cardiac death (SCD). By now, left-ventricular ejection fraction (LV-EF) is the main guideline criterion for primary prophylactic ICD implantation, potentially leading either to overtreatment or failed detection of patients at risk without severely impaired LV-EF. The aim of the European multi-center study DETECTIN-HF was to establish a clinical risk calculator for individualized risk stratification of DCM patients. Methods1393 patients (68% male, mean age 50.7 ± 14.3y) from four European countries were included. The outcome was occurrence of first potentially life-threatening ventricular arrhythmia. The model was developed using Cox proportional hazards, and internally validated using cross validation. The model included seven independent and easily accessible clinical parameters sex, history of non-sustained ventricular tachycardia, history of syncope, family history of cardiomyopathy, QRS duration, LV-EF, and history of atrial fibrillation. The model was also expanded to account for presence of LGE as the eight8h parameter for cases with available cMRI and scar information. ResultsDuring a mean follow-up period of 57.0 months, 193 (13.8%) patients experienced an arrhythmic event. The calibration slope of the developed model was 00.97 (95% CI 0.90–1.03) and the C-index was 0.72 (95% CI 0.71–0.73). Compared to current guidelines, the model was able to protect the same number of patients (5-year risk ≥8.5%) with 15% fewer ICD implantations. ConclusionsThis DCM-SVA risk model could improve decision making in primary prevention of SCD in non-ischemic DCM using easily accessible clinical information and will likely reduce overtreatment.

Management and outcomes of hypertrophic cardiomyopathy in young adults

Management of young adults with hypertrophic cardiomyopathy (HCM) is challenging. To evaluate the profile of young adults (16-25 years) with HCM included in the French prospective HCM registry. Patients were compared according to occurrence of major adverse cardiac events (MACE), comprising sudden cardiac death (SCD) events (implantable cardioverter defibrillator [ICD] discharge, SCD, sustained ventricular tachycardia), atrial fibrillation/embolic stroke, heart failure hospitalisation and unexplained syncope, at a mean follow-up of 4.4±2.2 years. At baseline, among 61 patients (20.5±3.0 years; 16 women, 26.2%), 13 (21.3%) had a prophylactic ICD, 24.6% a family history of SCD, 29.5% obstruction, 86.0% magnetic resonance imaging myocardial fibrosis, 11.8% abnormal exercise blood pressure and 52.8% a European Society of Cardiology (ESC) 5-year SCD score<4% (24.5%≥6%). At follow-up, 15 patients (24.6%; seven women; all with fibrosis) presented 17 MACE, comprising: SCD events (n=7, 41.2%; including three patients with an ICD, five with at least one SCD major classical risk factor and an ESC score≥5% and two with no risk factors and an ESC score<4%); atrial fibrillation/stroke (n=6, 35.3%); heart failure (n=1, 5.9%); syncope (n=3, 17.6%). An ICD was implanted in 11 patients (four for secondary prevention), but in only 61.5% of patients with a score≥6%. Only obstruction significantly increased MACE risk (odds ratio 3.96; P=0.035), with a non-significant trend towards a lower risk in men (OR 0.29; P=0.065). In young adults with HCM, MACE are common in the short term, especially in obstructive HCM and women, mostly arrhythmic in origin. Prophylactic ICD implantation is frequent and does not strictly follow the guidelines, while the use of European/USA guidelines is helpful but imperfect in identifying SCD risk.

Nocturnal respiratory rate predicts ICD benefit: A prospective, controlled, multicentre cohort study.

BackgroundImplantable cardioverter defibrillators (ICDs) prevent sudden cardiac death. ICD implantation decisions are currently based on reduced left ventricular ejection fraction (LVEF≤35%). However, in some patients, the non-arrhythmic death risk predominates thus diminishing ICD-therapy benefits. Based on previous observations, we tested the hypothesis that compared to the others, patients with nocturnal respiratory rate (NRR) ≥18 breaths per minute (brpm) benefit less from prophylactic ICD implantations.MethodsThis prospective cohort study was a pre-defined sub-study of EU-CERT-ICD trial conducted at 44 centers in 15 EU countries between May 12, 2014, and September 6, 2018. Patients with ischaemic or non-ischaemic cardiomyopathy were included if meeting primary prophylactic ICD implantation criteria. The primary endpoint was all-cause mortality. NRR was assessed blindly from pre-implantation 24-hour Holters. Multivariable models and propensity stratification evaluated the interaction between NRR and the ICD mortality effect. This study is registered with ClinicalTrials.gov (NCT0206419).FindingsOf the 2,247 EU-CERT-ICD patients, this sub-study included 1,971 with complete records. In 1,363 patients (61.7 (12) years; 244 women) an ICD was implanted; 608 patients (63.2 (12) years; 108 women) were treated conservatively. During a median 2.5-year follow-up, 202 (14.8%) and 95 (15.6%) patients died in the ICD and control groups, respectively. NRR statistically significantly interacted with the ICD mortality effect (p = 0.0070). While the 1,316 patients with NRR<18 brpm showed a marked ICD benefit on mortality (adjusted HR 0.529 (95% CI 0.376–0.746); p = 0.0003), no treatment effect was demonstrated in 655 patients with NRR≥18 brpm (adjusted HR 0.981 (95% CI 0.669–1.438); p = 0.9202).InterpretationIn the EU-CERT-ICD trial, patients with NRR≥18 brpm showed limited benefit from primary prophylactic ICD implantation. Those with NRR<18 brpm benefitted substantially.FundingEuropean Community's 7th Framework Programme FP7/2007-2013 (602299)

Clinical effectiveness of primary prevention implantable cardioverter-defibrillators: results of the EU-CERT-ICD controlled multicentre cohort study.

AimsThe EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter-Defibrillators (EU-CERT-ICD), a prospective investigator-initiated, controlled cohort study, was conducted in 44 centres and 15 European countries. It aimed to assess current clinical effectiveness of primary prevention ICD therapy.Methods and resultsWe recruited 2327 patients with ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and guideline indications for prophylactic ICD implantation. Primary endpoint was all-cause mortality. Clinical characteristics, medications, resting, and 12-lead Holter electrocardiograms (ECGs) were documented at enrolment baseline. Baseline and follow-up (FU) data from 2247 patients were analysable, 1516 patients before first ICD implantation (ICD group) and 731 patients without ICD serving as controls. Multivariable models and propensity scoring for adjustment were used to compare the two groups for mortality. During mean FU of 2.4 ± 1.1 years, 342 deaths occurred (6.3%/years annualized mortality, 5.6%/years in the ICD group vs. 9.2%/years in controls), favouring ICD treatment [unadjusted hazard ratio (HR) 0.682, 95% confidence interval (CI) 0.537–0.865, P = 0.0016]. Multivariable mortality predictors included age, left ventricular ejection fraction (LVEF), New York Heart Association class <III, and chronic obstructive pulmonary disease. Adjusted mortality associated with ICD vs. control was 27% lower (HR 0.731, 95% CI 0.569–0.938, P = 0.0140). Subgroup analyses indicated no ICD benefit in diabetics (adjusted HR = 0.945, P = 0.7797, P for interaction = 0.0887) or those aged ≥75 years (adjusted HR 1.063, P = 0.8206, P for interaction = 0.0902).ConclusionIn contemporary ICM/DCM patients (LVEF ≤35%, narrow QRS), primary prophylactic ICD treatment was associated with a 27% lower mortality after adjustment. There appear to be patients with less survival advantage, such as older patients or diabetics.

Prospective evaluation of outcome of Indian patients who meet MADIT II (Multicenter Automatic Defibrillator Implantation Trial) criteria for implantable cardioverter defibrillator implantation: is it appropriate for Indian patients?

BackgroundThe MADIT II investigators had concluded that prophylactic use of an ICD improved survival in patients with prior myocardial infarction reduced left ventricular ejection fraction. Whether MADIT II criteria for ICD implantation are appropriate for Indian patients also is unclear and not studied. MethodsA total of 144 patients, Mean age 56.23 ± 10.9 years who met MADIT II criteria were prospectively followed for 20.78 + 5.9 months. ResultsDuring the follow-up period, 26 (18.1%) patients died. 18 were sudden cardiac deaths and 8 were non SCD deaths. Total mortality did not correlate with Age, NYHA class, NSVT on Holter, PVC >10/hours, QRS width, or use of statins. Multivariate logistic regression model identified the following variables associated with increase all-cause mortality: No use of beta blocker (odd ratio:13.068, p = 0.021), No past revascularization (odd ratio:11.613,p = 0.007) and Increase serum creatinine level (odd ratio: 4.066, p = 0.035). The mortality rate in the present series was comparable with that in the MADIT II conventional therapy group though patient in present study are younger, less diabetic, hypertensive, smokers and better treated with beta-blockers, ACE/ARB and statin. ConclusionIndian patients with prior MI (more than one month back) and left ventricular ejection fraction of 30% or less had a cardiac mortality similar to western population who are not treated with prophylactic ICD. Patients of Indian origin should derive a similar benefit with prophylactic implantation of ICD as per MADIT II criteria as would a western population.

Early detection of ventricular arrhythmias in adults with congenital heart disease using an insertable cardiac monitor (EDVA-CHD study)

BackgroundSudden cardiac death (SCD) due to ventricular arrhythmias (VA) is an important mode of death in adults with congenital heart disease (CHD). Risk stratification is difficult in this heterogeneous population. Insertable cardiac monitors (ICM) may be useful for risk stratification. The purpose of the present study was to evaluate the use of ICM for the detection of VA in adults with CHD. MethodsIn this prospective single-center observational study we included consecutive adults with CHD deemed at risk of VA who received an ICM between March 2013 and February 2019. The decision to implant an ICM was made in a Heart Team consisting of a cardiac electrophysiologist and a cardiologist specialized in CHD. ResultsA total of 30 patients (mean age, 38 ± 15 years; 50% male) received an ICM. During a median follow-up of 16 months, 8 patients (27%) had documented nonsustained VA. Of these 8 patients, 3 (10%) received a prophylactic ICD. Furthermore, ICM-detected arrhythmias were present in 22 patients (73%) leading to a change in clinical management in 16 patients (53%). Besides the patients receiving an ICD, 10 patients (33%) had a change in their antiarrhythmic drugs, 6 patients (20%) underwent an electrophysiology study, and 1 patient (3%) received a pacemaker. ConclusionsThe detection of VA by the ICM contributed to the clinical decision to implant a prophylactic ICD. Furthermore, ICM-detected arrhythmias led to important changes in the clinical management. Therefore, long-term arrhythmia monitoring by an ICM seems valuable for risk stratification in adults with CHD.