Primary Prevention Implantable Cardioverter-defibrillator Research Articles

Mitral valve prolapse and mitral annulus disjunction: be aware of a potential arrhythmogenic substrate

Mitral valve prolapse is a relatively common disease with a good overall prognosis. However, in specific clinical and instrumental contexts, patients at high risk of ventricular arrhythmias and sudden cardiac death can be identified. Female sex, history of palpitations or syncope, bi-leaflet myxomatous valve, ECG repolarization abnormalities in the inferior leads, complex ventricular arrhythmias, left ventricular fibrosis detected by cardiac magnetic resonance correlate with a higher risk clinical profile. Additionally, morpho-functional abnormalities of the mitral valve annulus, particularly mitral annulus disjunction, may cause a mechanical stretch at the inferior basal ventricular wall and posterior papillary muscles, predisposing to myocardial fibrosis and arrhythmias. A risk stratification strategy is needed to identify patients with mitral valve prolapse and/or mitral annulus disjunction at high risk of arrhythmias; however, few data are available. Further prospective multicenter studies are warranted, focusing on medical therapy, the role of implantable cardioverter-defibrillators for primary prevention, efficacy of targeted catheter ablation or mitral valve surgery.

Reply to the Editor - Are we close to a major impact on prevention of sudden cardiac death among coronary artery disease patients?

We thank Doundoulakis and colleagues for their interest in our study demonstrating that ventricular tachycardia or ventricular fibrillation was the presenting rhythm in ∼50% of the in-hospital cardiac arrests among patients with heart failure with preserved ejection fraction (EF).1 Determining whether cardiac arrests occur owing to shockable arrhythmias is a key step in the quest to reduce sudden cardiac death (SCD) in heart failure with preserved EF.2 However, more work needs to be done to prevent SCD, particularly in patients with EF >35% who are not eligible for primary-prevention implantable cardioverter-defibrillator (ICD) therapy based on the current practice guidelines.

Disease progression rate is a strong predictor of ventricular arrhythmias in patients with cardiac laminopathy in a prospective cohort study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Area Network on Cardiovascular Diseases (ERA-CVD) Background/Introduction: Cardiac laminopathy is a highly malignant and pro-arrhythmic familial dilated cardiomyopathy, caused by LMNA gene mutations. The optimal timing of primary preventive implantable cardioverter defibrillator (ICD) is a challenge in this patient population. Purpose We aimed to explore whether disease progression rate assessed by echocardiography can predict ventricular arrhythmias in LMNA genotype positive patients, and to describe the cardiac phenotype at time of first ventricular arrhythmia. Methods We prospectively included consecutively recruited LMNA genotype positive patients in a primary prevention cohort study. Patients underwent repeated clinical and echocardiographic examinations during long-term follow-up. Ventricular arrhythmia was defined as sustained ventricular tachycardia, appropriate therapy by ICD or aborted cardiac arrest. We used generalized estimating equation analyses to assess whether individual patient disease progression could predict first-time ventricular arrhythmia. Graphical illustration of disease progression rate was presented as linear prediction by patient age. Cardiac function and volumes at time of ventricular arrhythmia was assessed from echocardiograms acquired ±12 months of the arrhythmic event. Results We included 94 patients with no ventricular arrhythmia at baseline (age 38 ± 15 years, 32% probands, 53% female). Nineteen (20%) patients experienced ventricular arrhythmia during 4.6 (inter quartile range 2.1-7.3) years follow-up, at mean age 50 ± 11 years. We analysed 536 echocardiographic examinations. Individual patient disease progression were strong predictors of subsequent ventricular arrhythmia with OR 1.3 (95% CI 1.2-1.5) per 5% reduction in left ventricular ejection fraction (LVEF), OR 1.3 (95% CI 1.2-1.5) per 1% worsened left ventricular global longitudinal strain (LVGLS), and OR 1.2 (95% CI 1.1-1.3) per 5 ml/m2 increase in left ventricular end diastolic volume index (LVEDVi). Comparison of disease progression by LVEF between patients with and without ventricular arrhythmias is illustrated in Figure. At arrhythmic event, there was left ventricular structural- and functional pathology (LVEF 40 ± 12%, LVGLS -11.7 ± 4.3%, LVEDVi 83 ± 22 ml/m2), while right ventricular function was preserved in most patients (tricuspid annular plane systolic excursion 20 ± 7 mm). Conclusions First time ventricular arrhythmic event occurred in 20% of LMNA genotype positive patients during 4.6 years of follow up. Individual patient disease progression by structural and functional parameters were strong predictors of ventricular arrhythmias, indicating that the disease progression rate may have additional value to absolute measurements when considering primary preventive ICD implantation. Abstract Figure

The impact of government-mandated shared decision-making for implantable defibrillators: A natural experiment.

In 2018, the Centers for Medicare and Medicaid Services (CMS) mandated that patients considering implantation of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death undergo shared decision-making (SDM) using a decision-aid. To observe the impact of the CMS's mandate on core measures of SDM using a natural experiment. Patients who underwent implantation of a primary prevention ICD within the Emory Healthcare system between 2017-2019 (pre and post SDM mandate) were surveyed. Survey domains included knowledge about the ICD, decisional conflict, values-choice concordance, and engagement in decision-making. Patients who had an ICD implant after the mandate were also asked about their views of the decision aid (DA). Responses of patients who had ICD implanted prior to the mandate were compared to those after the mandate using either Student t test or Chi-Squared tests. Of 101 patients who completed the survey, 45 had an ICD placed before the mandate and 56 had an ICD placed after. There were no major differences between knowledge, decisional conflict, values choice concordance, or patient engagement. Compared to patients with ICDs placed before the mandate, patients with ICDs after the mandate were more likely to subjectively feel more informed about the benefits of the procedure but were less likely to be able to correctly identify the frequency of complications. Policy effects to promote SDM that solely focus on a decision-aid may not substantively impact patient centered care.

Strength of clinical indication and therapeutic impact of the implantable cardioverter defibrillator in patients with hypertrophic cardiomyopathy

BackgroundThe implantable cardioverter defibrillator(ICD) has revolutionized the management of patients with hypertrophic cardiomyopathy (HCM) at risk of sudden cardiac death (SCD). However, the identification of ideal candidates remains challenging. We aimed to describe the long-term impact of the ICD for primary prevention in patients with HCM based on stringent (high SCD risk) vs lenient indications (need for pacing/personal choice). MethodsData from two Italian HCM Cardiomyopathy Units were retrospectively analyzed. Only patients >1 follow-up visits were divided into two groups according to ICD candidacy:stringent (high SCD risk) and lenient (need for pacing, patients' choice, physician advice despite lack of high SCD risk).Major cardiac events (composite of appropriate shock/intervention and SCD) was the primary endpoint. A safety endpoint was defined as a composite of inappropriate shocks and device-related complications. ResultsOf 2009 patients, 252(12.5%) received an ICD, including 27(1.3%) in secondary prevention and 225(11.2%) in primary prevention (age at implantation 49 ± 16 years; men 65.3%). Among those in primary prevention, 167(74.2%) had stringent, while 58(25.8%) had lenient indications.At 5 ± 4 years, only stringent ICD patients experienced major cardiac events (2.84%/year, 5-year cumulative incidence: 8.1%, 95%CI [3.5–14.1%]).ICD-related complications were similar across stringent and lenient subgroups. However, patients implanted >60 years had a significantly higher risk of adverse events. ConclusionOne third of ICD recipients with HCM in primary prevention received a lenient implantation and had no appropriate intervention. ICD implantation due to systematic upgrade in patients requiring pacing and increased risk perception may offer little advantage and increase complication rates.

Cardiovascular Characteristics of Patients with Genetic Variation in Desmoplakin (DSP).

Background:Variants in the desmoplakin (DSP) gene have been recognized in association with the pathogenesis of arrhythmogenic right ventricular cardiomyopathy (ARVC) for nearly 20 years. More recently, genetic variation in DSP has also been associated with left-dominant arrhythmogenic cardiomyopathy. Data regarding the cardiac phenotypes associated with genetic variation in DSP have been largely accumulated from phenotype-first studies of ARVC.Methods:We aimed to evaluate the clinical manifestations of cardiac disease associated with variants in DSP through a genotype-first approach employed in the University of Pennsylvania Center for Inherited Cardiovascular Disease registry. We performed a retrospective study of 19 individuals with “pathogenic” or “likely pathogenic” variants in DSP identified by clinical genetic testing. Demographics and clinical characteristics were collected.Results:Among individuals with disease-causing variants in DSP, nearly 40% had left ventricular enlargement at initial assessment. Malignant arrhythmias were prevalent in this cohort (42%) with a high proportion of individuals undergoing primary and secondary prevention implantable cardioverter defibrillator implantation (68%) and ablation of ventricular arrhythmias (16%). Probands also experienced end-stage heart failure requiring heart transplantation (11%).Conclusions:Our data suggest DSP cardiomyopathy may manifest with a high burden of heart failure and arrhythmic events, highlighting its importance in the pathogenesis of dilated and arrhythmogenic cardiomyopathies. Targeted strategies for diagnosis and risk stratification for DSP cardiomyopathy should be investigated.

Cardiac device implantation and device usage in Fabry and hypertrophic cardiomyopathy

BackgroundFabry disease (FD) is a treatable X-linked condition leading to progressive cardiac disease, arrhythmia and premature death. We aimed to increase awareness of the arrhythmogenicity of Fabry cardiomyopathy, by comparing device usage in patients with Fabry cardiomyopathy and sarcomeric HCM. All Fabry patients with an implantable cardioverter defibrillator (ICD) implanted in the UK over a 17 year period were included. A comparator group of HCM patients, with primary prevention ICD implantation, were captured from a regional registry database.ResultsIndications for ICD in FD varied with 72% implanted for primary prevention based on multiple potential risk factors. In FD and HCM primary prevention devices, arrhythmia occurred more frequently in FD over shorter follow-up (HR 4.2, p < 0.001). VT requiring therapy was more common in FD (HR 4.5, p = 0.002). Immediate shock therapy for sustained VT was also more common (HR 2.5, p < 0.001). There was a greater burden of AF needing anticoagulation and NSVT in FD (AF: HR 6.2, p = 0.004, NSVT: HR 3.1, p < 0.001).ConclusionThis study demonstrates arrhythmia burden and ICD usage in FD is high, suggesting that Fabry cardiomyopathy may be more ‘arrhythmogenic’ than previously thought. Existing risk models cannot be mutually applicable and further research is needed to provide clarity in managing Fabry patients with cardiac involvement.

A Retrospective Audit to Determine the Outpatient Waiting Period for Primary Prevention Implantable Cardioverter Defibrillators at a Single Centre Over 12 Years

Since the clinical trials that define our current guidelines regarding implantation of primary prevention cardioverter-defibrillators (ICD) in ischaemic and non-ischaemic cardiomyopathy, there have been improvements in medical therapy and invasive management of coronary artery disease [1]. Existing guidelines may no longer be applicable to stratifying the risk of sudden cardiac death in the modern era.

Infiltrating cardiomyopathy presenting with recurrent ventricular tachycardia

Abstract Infiltrative cardiomyopathy (ICM) refers to a heterogeneous group of myocardial disorders mainly cardiac amyloidosis, sarcoidosis, and hemochromatosis with characteristic deposition of abnormal substances within cellular and intercellular spaces, which leads to the development of ventricular diastolic dysfunction, systolic dysfunction, or both. Sarcoidosis is a multisystem, granulomatous disease of unknown etiology. Accumulating evidence suggests that it is caused by an immunological response to an unidentified antigenic trigger in genetically susceptible persons. Cardiac sarcoidosis is a manifestation of sarcoidosis that is challenging to diagnose due to its clinical silence. The consequences of cardiac sarcoidosis include conduction defects, arrhythmias, cardiomyopathy, congestive heart failure, and sudden cardiac death (SCD). This case describes a 45-year-old female with a history of recurrent ventricular tachycardia in a patient previously diagnosed as dilated nonischemic cardiomyopathy. Who was later diagnosed as ICM, most probably cardiac sarcoidosis with the help of cardiac magnetic resonance imaging (MRI). Initial testing for infiltrating cardiomyopathy should include echocardiography, cardiac MRI, and fluorodeoxyglucose–positron emission tomography study. Treatment focuses on optimizing heart failure therapy and placement of a biventricular implantable cardioverter-defibrillator for primary prevention of SCD.

Arrhythmic and Mortality Outcomes Among Ischemic Versus Nonischemic Cardiomyopathy Patients Receiving Primary ICD Therapy.

This study sought to determine the association of cardiomyopathy etiology with the likelihood of ventricular arrhythmias, appropriate implantable cardioverter-defibrillator (ICD) therapy, and mortality. There are conflicting data on the benefit of primary prevention ICD therapy in patients with ischemic versus nonischemic cardiomyopathy (ICM/NICM). The study population comprised 4803 patients with ICM (n=3,106) or NICM (n=1,697) with a primary prevention ICD enrolled in 5 randomized trials conducted between 1997 and 2017. The primary end point was sustained ventricular tachycardia (VT)≥200 beats/min or ventricular fibrillation (VF). Secondary end points included appropriate ICD therapy and all-cause mortality. Differences in cause-specific mortality, including noncardiac, sudden cardiac, and non-sudden cardiac death, were also examined. Patients with ICM were significantly older and had more comorbid conditions, whereas those with NICM had a more advanced heart failure class at enrollment and were more often prescribed medical or cardiac resynchronization therapy for heart failure. Multivariate analysis showed that ICM versus NICM had a similar risk of VT/VF events (HR: 0.98 [95%CI: 0.79-1.20]) and appropriate ICD therapy (HR: 1.03 [95%CI: 0.87-1.22]), whereas the risk of all-cause mortality was 1.8-fold higher among ICM versus NICM patients (HR: 1.84 [95%CI: 1.42-2.38]), dominated by non-sudden cardiac mortality. Combined data from 5 landmark ICD clinical trials show that ICM patients experience a similar risk of life-threatening ventricular arrhythmic events but have an increased risk of all-cause mortality, dominated by non-sudden cardiac death, compared with NICM patients.

Prediction of early death after myocardial infarction in patients with reduced left ventricular ejection fraction. The search for new indications for cardioverter-defibrillator implantation (ICD)

The highest rate of death is in the first few weeks after myocardial infarction (MI). However, the assessment of indications for primary prevention implantable cardioverter-defibrillator (ICD) implantation should be postponed until at least 40 days after MI. Our aim was to identify the subgroup of high-risk patients with reduced left ventricular ejection fraction (LVEF) who would benefit from primary prevention ICD implantation within 40 days of MI. Out of 205 606 patients with MI, in this study, we included 18 736 patients treated invasively, with LVEF <40%, who survived until hospital discharge. Patients were divided into two groups according to the survival status at 40 days - patients who died within this period (n = 1331) and patients who survived (n = 17405). Among all patients who died within 12-months after MI, 37.7% did die during the first 40 days. Patients with cardiac arrest before hospital admission or within the first 48 hours of hospitalization (hazard ratio [HR], 3.35; 95% confidence interval [CI], 2.82-3.98; P <0.0001], cardiogenic shock before admission or during hospitalization (HR, 3.06; 95% CI, 2.62-3.59; P <0.0001), unsuccessful percutaneous coronary interventions (PCI; HR, 2.42; 95% CI, 2.11-2.84; P <0.0001), LVEF <20% (ref. LVEF ≥30%; HR, 2.75; 95% CI, 2.25-3.36; P <0.0001) had approximately threefold and patients with chronic kidney disease almost 1.5-times (HR, 1.25; 95% CI, 1.47-3.59; P = 0.0053) higher 40-day mortality compared to patients without these risk factors. The most striking differences in mortality between these subgroups were observed shortly after discharge. The highest risk of death in patients with reduced LVEF who survived until hospital discharge occurred within the first 40 days after MI. There is a possibility to select patients with the worst prognosis and treat them more aggressively.

EACVI survey on hypertrophic cardiomyopathy

The European Association of Cardiovascular Imaging (EACVI) Scientific Initiatives Committee performed a global survey to evaluate current practice for the assessment and management of patients with hypertrophic cardiomyopathy (HCM). A total of 213 centres from 38 different countries (87% European) responded to the survey. One hundred twenty-one (57%) centres followed HCM patients in a general cardiology outpatient clinic and 85 (40%) centres in a specialized HCM/cardiomyopathy clinic. While echocardiography was the primary imaging modality, cardiovascular magnetic resonance (CMR) has become an important complementary tool. Cardiac anatomy, left ventricular (LV) systolic, and diastolic function were assessed according to current European guidelines and recommendations. To evaluate LV obstruction, 49% of the centres performed bedside provocation manoeuvres in every patient and 55% of the centres used exercise stress echocardiography. The majority of centres used the 5-year risk assessment of sudden cardiac death (SCD) calculated with the HCM Risk-SCD score. However, 34% of the centres also used extensive non-infarct late gadolinium enhancement on CMR and 27% the presence of LV apical aneurysm to help select patients for primary prevention implantable cardioverter-defibrillator therapy. Ninety-nine percent of the responding centres performed regular imaging follow-up of HCM patients. Most centres followed European guidelines and recommendations for the diagnosis and management of patients with HCM. The importance of bedside provocation manoeuvres and exercise stress echocardiography to diagnose LV outflow obstruction requires emphasis. Additional risk markers for SCD are used in many centres and might indicate the need for an update of current European recommendations.

Sacubitril/valsartan reduces indications for arrhythmic primary prevention in heart failure with reduced ejection fraction: insights from DISCOVER-ARNI, a multicenterItalian register.

AimsThis sub-study deriving from a multicentre Italian register [Deformation Imaging by Strain in Chronic Heart Failure Over Sacubitril-Valsartan: A Multicenter Echocardiographic Registry (DISCOVER)-ARNI] investigated whether sacubitril/valsartan in addition to optimal medical therapy (OMT) could reduce the rate of implantable cardioverter-defibrillator (ICD) indications for primary prevention in heart failure with reduced ejection fraction (HFrEF) according to European guidelines indications, and its potential predictors.Methods and resultsIn this observational study, consecutive patients with HFrEF eligible for sacubitril/valsartan from 13 Italian centres were included. Lack of follow-up or speckle tracking data represented exclusion criteria. Demographic, clinical, biochemical, and echocardiographic data were collected at baseline and after 6 months from sacubitril/valsartan initiation. Of 351 patients, 225 (64%) were ICD carriers and 126 (36%) were not ICD carriers (of whom 13 had no indication) at baseline. After 6 months of sacubitril/valsartan, among 113 non-ICD carriers despite having baseline left ventricular (LV) ejection fraction (EF) ≤ 35% and New York Heart Association (NYHA) class = II–III, 69 (60%) did not show ICD indications; 44 (40%) still fulfilled ICD criteria. Age, atrial fibrillation, mitral regurgitation > moderate, left atrial volume index (LAVi), and LV global longitudinal strain (GLS) significantly varied between the groups. With receiver operating characteristic curves, age ≥ 75 years, LAVi ≥ 42 mL/m2 and LV GLS ≥−8.3% were associated with ICD indications persistence (area under the curve = 0.65, 0.68, 0.68, respectively). With univariate and multivariate analysis, only LV GLS emerged as significant predictor of ICD indications at follow-up in different predictive models.ConclusionsSacubitril/valsartan may provide early improvement of NYHA class and LVEF, reducing the possible number of implanted ICD for primary prevention in HFrEF. Baseline reduced LV GLS was a strong marker of ICD indication despite OMT. Early therapy with sacubitril/valsartan may save infective/haemorrhagic risks and unnecessary costs deriving from ICDs.

Improvement of left ventricular function with surgical revascularization in patients eligible for implantable cardioverter-defibrillator.

Left ventricular ejection fraction (EF) ≤ 35% is the cornerstone criterion for implantable cardioverter-defibrillator (ICD) eligibility. Improvement in EF may occur in ICD-eligible patients after coronary artery bypass graft surgery (CABG). However, the incidence, predictors, and outcomes of this process are unclear. We studied 427 patients with EF ≤ 35% who underwent CABG in the Surgical Treatment for Ischemic Heart Failure (STICH) trial and had a systematic pre- and postoperative (4 months) EF assessment using the identical cardiac imaging modality. All imaging studies were interpreted at a core laboratory. Improvement in EF was defined as postoperative EF > 35% and >5% absolute improvement from baseline. Of the 427 patients (mean age 61.8 ± 9.5 and 50 women), 125 (29.2%) had EF improvement. Their mean EF increased from 26.8% (±5.8%) to 43.3% (±6.5%) (p < .0001). EF improvement occurred in only 20% of patients with a preoperative EF < 25%. The odds of EF improvement were 1.96 times higher (95% confidence interval [CI]: 0.91-4.23, p = .09) in patients with myocardial viability. In adjusted analyses, EF improvement was associated with a significantly lower risk of all-cause mortality (hazard ratio [HR]: 0.58, 95% CI: 0.35-0.96; p = .03) and heart failure mortality (HR: 0.31, 95% CI: 0.11-0.87; p = .027). Nearly 1/3rd of ICD-eligible patients undergoing CABG had significant improvement in EF, obviating the need for primary prevention ICD implantation. These results provide patients and clinicians data on the likelihood of ICD eligibility after CABG and support the practice of reassessment of EF after revascularization.

279 Medical treatment with ARNI may reduce indications for primary prevention of sudden cardiac death in heart failure with reduced ejection fraction: insights from discover-ARNI, a multicentre Italian register

Abstract Aims This sub-study deriving from a multicentre Italian register (DISCOVER-ARNI) investigated whether sacubitril/valsartan in adjunction of optimal medical therapy (OMT) could reduce the rate of implantable cardioverter-defibrillator(ICD) indications for primary prevention in heart failure with reduced ejection fraction (HFrEF) according to European guidelines indications, and its potential predictors. Methods and results In this observational study, consecutive patients with HFrEF eligible for sacubitril/valsartan from 13 Italian centres were included. Lack of follow-up or speckle tracking data represented exclusion criteria. Demographic, clinical, biochemical and echocardiographic data were collected at baseline and after 6 months of therapy. Of 351 patients, 225 (64%) were ICD carriers and 126 (36%) were not ICD carriers (of whom 13 had not indication) at baseline. After 6 months of sacubitril/valsartan, among 113 non-ICD carriers despite having baseline left ventricular (LV)EF ≤ 35% and New York Heart Association (NYHA) class = II–III, 69(60%) did not show ICD indications; 44(40%) still fulfilled ICD criteria (Figure 1). Age, atrial fibrillation, mitral regurgitation&amp;gt;moderate, left atrial volume index (LAVi), and LV global longitudinal strain (GLS) significantly varied between the groups. With ROC curves, age ≥ 75 years, LAVi ≥ 42 ml/m2 and LV GLS ≥ −8.3% were associated with ICD indications persistence (AUC = 0.65, 0.68, and 0.68, respectively). With univariate and multivariate analysis, age and LV GLS emerged as the only significant predictors of ICD indications at follow-up. Conclusions Sacubitril/valsartan provided early improvement of NYHA class and LVEF, reducing the possible number of implanted ICD for primary prevention in HFrEF. Baseline advanced age and reduced LV GLS were markers of ICD indication despite OMT. Early therapy with sacubitril/valsartan may save infective/haemorrhagic risks and unnecessary costs deriving from ICDs.

564 Controversial role of intracardiac eletrophysiology study in Brugada syndrome: analysis of a single-centre retrospective cohort study

Abstract Aims According to European guidelines, aborted sudden cardiac death (SCD) in Brugada syndrome (BrS) is regarded as a I class recommendation for secondary prevention implantable cardioverter defibrillator (ICD). However, the risk stratification of BrS patients for primary prevention ICD still represents a clinical conundrum. Although intracardiac electrophysiology (EP) study proved useful for the selection of high-risk patients in this setting. Therefore, aim of this study was to assess all clinical and EP variables associated with the induction of VA at EP study and the rate of appropriate/inappropriate ICD interventions and/or clinical SCD events in these patients occurring at follow-up. Methods and results From 2001 to 2021, all EP studies performed in symptomatic/asymptomatic patients (46 ± 14 years, M 88%) with/without family history of SCD spontaneous/drug-induced type I pattern (TIP) on ECG and no spontaneous ventricular arrhythmias were retrospectively considered at our study centre. Clinical variables, BrS pattern, EP study data (including right ventricular site and type of stimulation protocol), and ICD interventions (DC-shocks or Anti-Tachycardia Pacing events, ATP) and/or SCD events occurring at follow-up were all evaluated. EP study was deemed positive for any polymorphic VA induced during programmed ventricular stimulation; non-sustained episodes included. ICD was routinely implanted in all patients with a positive EP study. Follow-up data were detected by the collection of medical and home-monitoring recordings at study-site level. Follow-up data were available in 50 patients (9 ± 6 years on average). Patients were generally young with few cardiovascular comorbidities. SCD history was known in 21 (42%) with a significant number of asymptomatic patients (48%). Br patterns were equally distributed in the investigated population (spontaneous and drug-induced TIP in 52% and 48%, respectively) and AF history was fairly common (16%). In the study population, EP study tested positive in 30 patients (60%): spontaneous TIP (P = 0.0518), few extrastimuli during programmed ventricular stimulation (P = 0.0015), and right ventricular stimulation at the apical site (P ≤ 0.0001) were the only variables to be clearly associated with a positive EP study in the appraised patients. At follow-up, appropriate ICD shocks were documented in 4 out of 30 implanted patients (13%) at generally 5 ± 7 years from EP study evaluation. Although three ICD interventions (75%) occurred in patients with spontaneous TIP, one patient with drug-induced TIP pattern and positive EP study referred to Emergency Department for unrelenting VT storm after roughly 13 years from ICD implantation. Inappropriate ICD interventions for fast rate AF were detected in 10% of cases. Finally, no SCD events were documented at follow up in patients with a negative EP study. Conclusions In a retrospective analysis, EP study proved useful in the risk stratification of SCD in BrS patients. A few ventricular extrastimuli delivered at the right ventricular apex seem sufficient to prompt the induction of life-threatening VA in high-risk BrS patients during EP study. Moreover, in this setting, a negative EP study seems protective against the development of VA/SCD events at follow-up. However, not only is spontaneous TIP associated with an increased risk of arrhythmic death, but a drug-induced TIP, generally regarded as a low-risk condition, might also be associated with a long-term hazard of SCD in these patients.

Mode of death and outcomes of implantable cardioverter defibrillators in transthyretin amyloid cardiomyopathy

IntroductionTransthyretin cardiac amyloidosis (ATTR-CM) may associate with sudden cardiac death. We report on the mode of death and outcomes with implantable cardioverter defibrillators (ICDs) in a cohort with ATTR-CM. MethodsA single center observational cohort study of patients with ATTR-CM diagnosed between 2005 and 2019. ICD implant was at discretion of treating cardiologists. Medians are expressed with 25th,75th percentiles. ResultsEighty-four patients with ATTR-CM (age 73.5 ± 9.7 years, 94% male, median follow-up 21.1 months (11.4–38.1). Nineteen patients (23%) underwent ICD implantation – 18 for primary and 1 for secondary prevention. In the primary prevention ICD group, 1 patient had 2 inappropriate shocks, 1 patient had appropriate ATP on 3 occasions. One patient (mixed ischemic cardiomyopathy and ATTR-CM) with secondary prevention ICD had 15 appropriate shocks in 3 episodes of VT storm. In patients without ICD, ambulatory monitoring review (14,764 h) did not reveal sustained ventricular arrhythmia. Excluding the one patient with secondary prevention ICD, 5 (28%) in the primary prevention ICD group and 22 (34%) in the non-ICD group died, p = 0.14. Mode of death did not vary between both groups. ConclusionsPatients with ATTR-CM and primary prevention ICD infrequently receive appropriate device therapy without differing in mode of death, which was mainly related to progressive heart failure, compared to those without ICD.

CinE caRdiac magneTic resonAnce to predIct veNTricular arrhYthmia (CERTAINTY)

Better models to identify individuals at low risk of ventricular arrhythmia (VA) are needed for implantable cardioverter-defibrillator (ICD) candidates to mitigate the risk of ICD-related complications. We designed the CERTAINTY study (CinE caRdiac magneTic resonAnce to predIct veNTricular arrhYthmia) with deep learning for VA risk prediction from cine cardiac magnetic resonance (CMR). Using a training cohort of primary prevention ICD recipients (n = 350, 97 women, median age 59 years, 178 ischemic cardiomyopathy) who underwent CMR immediately prior to ICD implantation, we developed two neural networks: Cine Fingerprint Extractor and Risk Predictor. The former extracts cardiac structure and function features from cine CMR in a form of cine fingerprint in a fully unsupervised fashion, and the latter takes in the cine fingerprint and outputs disease outcomes as a cine risk score. Patients with VA (n = 96) had a significantly higher cine risk score than those without VA. Multivariate analysis showed that the cine risk score was significantly associated with VA after adjusting for clinical characteristics, cardiac structure and function including CMR-derived scar extent. These findings indicate that non-contrast, cine CMR inherently contains features to improve VA risk prediction in primary prevention ICD candidates. We solicit participation from multiple centers for external validation.

Abstract 11977: Cardiac Resynchronization Therapy and the Risk of Ventricular Tachyarrhythmia

Introduction: Cardiac Resynchronization Therapy (CRT) was shown to be associated with clinically significant benefit by lowering mortality, heart failure hospitalizations, and improving quality of life in patients with reduced left ventricular function and a wide QRS. However, there are conflicting data on the effect of CRT on the risk of ventricular tachycardia or ventricular fibrillation (VT/VF) in implantable cardioverter defibrillator (ICD) recipients. Methods: The study population comprised 4531 patients enrolled in the 5 landmark ICD trials (MADIT-II, MADIT-CRT, MADIT-RIT, MADIT-RISK, and RAID) implanted with an ICD. Three patient groups were generated: ICD with a narrow QRS complex (n=2208), ICD alone with a wide QRS (n=1105), and patients with both ICD and a CRT (CRT-D) (n=2198). We compared the cumulative incidence of VT/VF in each group while accounting for the competing risk of non-arrhythmic mortality using the Fine and Gray Method. Results: Recipients of a CRT-D were more likely to be female, to use a beta blocker, and have a higher New York Heart Association Functional Class. The cumulative incidence of VT/VF at 4 years of follow-up in patients with a CRT-D was significantly lower (24%) as compared with patients with an ICD with or without a wide QRS (31% for both; p&lt;0.001 for the overall difference). Findings were consistent for the endpoints of appropriate ICD shocks and fast VT/VF (&gt;200 bpm). Multivariate analysis showed that compared to ICD-only therapy (with wide QRS), treatment with CRT-D was associated with a significant 20% (p=0.006), in the endpoint of VT/VF and 36% reduction in the endpoint of appropriate shock for VT/VF (p&lt;0.001). Conclusion: Our data from 5 landmark clinical trials suggest that cardiac resynchronization therapy exerts important antiarrhythmic properties, leading to a significant reduction in the risk of ventricular tachyarrhythmia and appropriate ICD shocks in patients implanted with an ICD for primary prevention.

Abstract 14170: Incremental Value of Magnetic Resonance-Based Ventricular and Atrial Strain in Predicting Ventricular Arrhythmia

Introduction: Only a small subset of patients with primary prevention ICDs, for whom left ventricular ejection fraction (LVEF) is emphasized in current guidelines, receive appropriate ICD therapy. Objectives: To study the incremental value of cardiovascular MR (CMR)-derived right and left ventricular and left atrial strain measured using feature tracking in predicting ventricular arrhythmia in patients eligible for implantable cardioverter-defibrillator (ICD) primary prevention of ventricular arrhythmia. Methods: The study included patients who met the current clinical guideline to receive an ICD for primary prevention of SCD. CMR imaging was performed on either a 1.5 or a 3T scanner, including standard evaluation of LV function and structure, LV/RV/LA strains, LGE. Outcomes were comprised of 1) unstable VT/VF &gt;30sesonds, 2) appropriate ICD therapy; shock or anti-tachycardia pacing for VT/VF, or 3) SCD. The primary outcome was a composite endpoint of any of the above three outcomes. Results: A total of 239 patients were included and the average age was 57±14 years old. Patients with outcomes had slightly lower RV global longitudinal strain (GLS). Univariate Cox proportional hazards regression showed that every standard deviation increase in RV GLS was associated with a 73% increase in risk (p&lt; 0.01). The baseline multivariable Cox’s proportional hazards regression model with a standardized clinical risk score, standardized LVEF, LGE had an AUC of 0.64. The best performing model, which included standardized LV and RV GLS, significantly improved prognosis compared with the baseline model, with an AUC of 0.72 and a categorical free NRI of 0.88 (p=0.04). Model 1 indicated an increased risk of 77% for every standard deviation increase in RV GLS (p&lt; 0.01) and a decreased risk of 49% for every standard deviation increase in LV GLS (p= 0.02). Kaplan-Meier curves could be stratified using the selected thresholds; LV GCS ≥ 5.3 and RV GLS ≥ -10.8, respectively (p=0.02, p&lt;0.01).