Arrhythmic Event Rate Research Articles

Kiosk 4R-TC-09 - Myocardial Scar Characteristics by 3D-LGE Cannot Fully Explain Different Arrhythmic Event Rates in Primary and Secondary Prevention of Sudden Cardiac Death

Kiosk 4R-TC-09 - Myocardial Scar Characteristics by 3D-LGE Cannot Fully Explain Different Arrhythmic Event Rates in Primary and Secondary Prevention of Sudden Cardiac Death

Myocardial scar characteristics by 3D-LGE cannot fully explain different arrhythmic event rates in primary and secondary prevention of sudden cardiac death

Abstract Background There is a noticeable difference in the incidence of ventricular arrhythmias among patients receiving defibrillator devices (ICD or CRT-D) for primary vs. secondary prevention of sudden cardiac death (SCD). The underlying reasons for this difference remain to be fully explained. Purpose To assess for differences in myocardial scar characteristics between patients who had defibrillator devices implanted in primary vs. secondary prevention scenarios, and their correlation with arrhythmic events. Methods In this single center retrospective study, patients who underwent late gadolinium enhancement (LGE) cardiac MRI for clinical purposes before the implantation of an ICD or CRT-D were included. Patients with channelopathies (n=2) or inappropriate imaging quality (n=7) were excluded. We used ADAS software to perform myocardial scar characterization in 3D-LGE datasets in all but 16 patients, in which 2D datasets were used. The primary endpoint was a composite of appropriate ICD therapy (appropriate shock or ATP), sustained ventricular tachycardia or SCD. Results A total of 116 patients (mean age 66±14 years, 81% male) were included, 40 (35%) with devices implanted in secondary prevention. During a median follow-up of 28 months (IQR 16-24), 23 events were identified (18 appropriate ICD therapy, 9 shocks and 9 ATP; 2 SCD; 3 sustained VT), 7 of which (30.4%) in the primary prevention group, and 16 (69.6%) in the secondary prevention group. The event rate was significantly higher in the secondary prevention setting (15.0 events per 100 persons-year [95% CI 7.7 – 22.4] vs. 4.1 events per 100 persons-year [95% CI 1.1 – 7.1]; p < 0.001). Despite a higher LVEF in the secondary prevention group (41 ± 14% vs. 30 ± 13%; p-value < 0.001), no statistically significant differences were found regarding scar tissue characteristics, namely scar and borderzone (BZ) mass, total channel mass, largest channel mass, number of channels and scar heterogeneity (BZ mass / scar mass ratio) – Table. Conclusion Despite the higher event rate in patients receiving defibrillator devices in secondary vs. prevention, no differences in myocardial scar characteristics were found between both groups. These findings suggest that arrhythmic risk is unlikely to be explained solely by the anatomical substrate, and support a greater role for the interplay between substrate and transient triggers.

Catecholaminergic Polymorphic Ventricular Tachycardia: A Review of Therapeutic Strategies.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by bidirectional or polymorphic ventricular arrhythmia provoked by exercise or emotion. Most cases are caused by pathogenic variants in the gene encoding the cardiac ryanodine receptor (RYR2). The options for treating patients with CPVT have increased during the years, and evidence suggests that these have led to lower arrhythmic event rates. In addition, numerous potential new therapies are being investigated. In this review, we summarize the state of knowledge on both established and potential future treatment strategies for patients with CPVT and describe our approach to their management.

Evaluation of chronic drug-induced electrophysiological and cytotoxic effects using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).

Introduction: Cardiotoxicity is one of the leading causes of compound attrition during drug development. Most in vitro screening platforms aim at detecting acute cardio-electrophysiological changes and drug-induced chronic functional alterations are often not studied in the early stage of drug development. Therefore, we developed an assay using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that evaluates both drug-induced acute and delayed electrophysiological and cytotoxic effects of reference compounds with clinically known cardiac outcomes. Methods: hiPSC-CMs were seeded in 48-well multielectrode array (MEA) plates and were treated with four doses of reference compounds (covering and exceeding clinical free plasma peak concentrations -fCmax values) and MEA recordings were conducted for 4days. Functional-electrophysiological (field-potentials) and viability (impedance) parameters were recorded with a MEA machine. Results: To assess this platform, we tested tyrosine-kinase inhibitors with high-cardiac risk profile (sunitinib, vandetanib and nilotinib) and low-cardiac risk (erlotinib), as well as known classic cardiac toxic drugs (doxorubicin and BMS-986094), ion-channel trafficking inhibitors (pentamidine, probucol and arsenic trioxide) and compounds without known clinical cardiotoxicity (amoxicillin, cetirizine, captopril and aspirin). By evaluating the effects of these compounds on MEA parameters, the assay was mostly able to recapitulate different drug-induced cardiotoxicities, represented by a prolongation of the field potential, changes in beating rate and presence of arrhythmic events in acute (<2h) or delayed phase ≥24h, and/or reduction of impedance during the delayed phase (≥24h). Furthermore, a few reference compounds were tested in hiPSC-CMs using fluorescence- and luminescence-based plate reader assays, confirming the presence or absence of cytotoxic effects, linked to changes of the impedance parameters measured in the MEA assay. Of note, some cardiotoxic effects could not be identified at acute time points (<2h) but were clearly detected after 24h, reinforcing the importance of chronic drug evaluation. Discussion: In conclusion, the evaluation of chronic drug-induced cardiotoxicity using a hiPSC-CMs in vitro assay can contribute to the early de-risking of compounds and help optimize the drug development process.

Utility of cardiac magnetic resonance in assessing arrhythmic risk in patients with non ischemic cardiomyopathy undergoing biventricular pacing

Abstract Funding Acknowledgements Type of funding sources: None. Background Non-ischemic cardiomyopathy (NICM) is a common heart muscle disorder, which is responsible for approximately one-third of heart failure and is associated with significant morbidity and mortality. Recent data suggested the lack of mortality reduction from adding a defibrillator to cardiac resynchronization therapy (CRT) in all patients with NICM. Myocardial fibrosis detected by cardiac magnetic resonance late gadolinium enhancement (CMR-LGE) can help risk stratify patients who would benefit from adding a defibrillator to CRT in this patient population. Purpose We aim at assessing the relationship between the presence of myocardial fibrosis detected by CMR-LGE and the rate of major arrhythmic events (MAE) that included sustained VT, appropriate CRT-D intervention, VF, and SCD in patients with NICM undergoing (CRT) and to compare all-cause mortality and heart failure improvement between patients who receiving CRT-P vs those who receiving CRT-D based on the presence of myocardial fibrosis. Methods All consecutive patients with NICM satisfying a guideline directed indication for CRT implantation were included in the study after excluding patients who refused to consent, patients with acute decompensated heart failure and those contraindicated for a CMR. Patients were divided into two groups according to presence of fibrosis in cardiac MRI into (CRT-D/LGE) group and CRT-P/No LGE group and followed along for one year. Results Sixty patients were enrolled. Sixteen patients (26.6%) developed MAE during the study duration. Seven patients had myocardial fibrosis (receiving CRT-D as per protocol), while only nine patients had no myocardial fibrosis (receiving CRT-P as per protocol), (41.2% vs 20.9%, P=0.045). Presence of CMR-LGE, regardless the extent and distribution, predicted MAE with odd ratio 2.6 (CI=1.78-8.9, P=0.04). The presence of ≥7.5 % of myocardial fibrosis by CMR was associated with 54 % sensitivity and 100% specificity for MAE in the study population (Figure 1). However, All-cause mortality was significantly higher in the (CRT-P/No LGE) group vs (CRT-D/LGE) group [15 (34.9%) vs 2 (11.8%), P=0.076]. Comparison between both groups regarding symptoms of heart failure, QoL and ejection fraction is shown in Table 1. Conclusion In patients with NICM candidates for biventricular pacing, the presence of LGE on CMR, irrespective of the extent or segmental pattern, is independently associated with a major arrhythmic event and is associated with worse heart failure outcome. However, the absence of LGE did not rule out MAE and implanting CRT-P based on lack of fibrosis may result in higher all-cause mortality.

In-hospital predictors for primary prevention of sudden death after acute myocardial infarction with cardiac dysfunction

BackgroundCurrent guidelines recommend prophylactic defibrillator implantation in patients with acute myocardial infarction (AMI) and left ventricular ejection fraction (LVEF) ≤40 % or LVEF ≤35 % plus heart failure symptoms or inducible ventricular tachyarrhythmias during an electrophysiology study at 40 days after AMI or 90 days after revascularization. In-hospital predictors of sudden cardiac death (SCD) after AMI during the index hospitalization remain unsettled. We sought to examine in-hospital predictors of SCD in patients with AMI and LVEF ≤40 % evaluated during the index hospitalization. MethodsWe retrospectively evaluated 441 consecutive patients with AMI and LVEF ≤40 % admitted to our hospital between 2001 and 2014 (77 % male gender; median age: 70 years; median hospitalization length: 23 days). The primary endpoint was a composite of SCD or aborted SCD at ≥30 days after AMI onset (composite arrhythmic event). LVEF and QRS duration (QRSd) on electrocardiography were measured at a median of 12 days and 18 days, respectively. ResultsDuring a median follow-up of 7.6 years, the incidence of composite arrhythmic events was 7.3 % (32 of 441 patients). In multivariable analysis, QRSd ≥100 msec (beta-coefficient = 1.54, p = 0.003), LVEF ≤23 % (beta-coefficient = 1.14, p = 0.007), and onset-reperfusion time > 5.5 h (beta-coefficient = 1.16, p = 0.035) were independent predictors of composite arrhythmic events. The combination of these 3 factors was associated with the highest rate of composite arrhythmic events compared with 0–2 factors (p < 0.001). ConclusionsThe combination of QRSd ≥100 msec, LVEF ≤23 %, and onset-reperfusion time > 5.5 h during the index hospitalization provides precise risk stratification for SCD in patients early after AMI.

PO-04-139 THE CLINICAL COURSE OF GENOTYPE-POSITIVE PHENOTYPE-NEGATIVE PATIENTS WITH RYR2-MEDIATED CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but potentially lethal inherited cardiac arrhythmia, mostly associated with RYR2 variants. Data on phenotype-negative patients with a RYR2 variant, a growing population due to cascade screening, are lacking. We aimed to assess the clinical course of phenotype-negative patients with a RYR2 variant. All patients from the International CPVT Registry with a (likely) pathogenic RYR2 variant who were asymptomatic (defined as absence of syncope or sudden cardiac arrest [SCA]) were included if they had a negative phenotype (defined as absence of any ventricular ectopy) on baseline exercise stress test (EST) off anti-arrhythmic drugs. All ESTs during follow-up were assessed for the development of a phenotype, and data on arrhythmic events (defined as syncope, appropriate implantable cardioverter defibrillator (ICD) shock, SCA, and sudden cardiac death) during follow-up were collected. One-hundred-four patients were included (median age at first cardiologic examination 17.9 [IQR 10.4-39.2] years, 55 (52.9%) females, from 35 families with 30 different RYR2 variants). During a median follow-up duration of 6.1 [IQR 3.0-9.1] years, 449 ESTs of 79 patients were collected. When censoring at the last EST, 50.2% (95% CI 38.7-62.9) of the patients developed a phenotype at 5 years follow-up (Figure), including 25 on beta-blocker therapy. During follow-up, the overall arrhythmic event-rate was 0.010 per person year. Four (3.8%) patients experienced a syncope, of whom one was untreated and three were treated with a β1-selective beta-blocker, including one with confirmed non-adherence. Two of 3 patients with ESTs during follow-up prior to syncope had developed a phenotype. One showed a phenotype immediately after the event. One patient who had become phenotype-positive experienced a recurrent event (appropriate ICD shock). One (1.0%) patient had a SCA while being phenotype-positive and non-adherent to beta-blocker and flecainide. Twenty-nine patients never received medical therapy and were event-free during a median follow-up duration of 3.9 [IQR: 0.2-9.7] years. Following the initial phenotype-negative screening, approximately half of the patients with a RYR2 variant developed a phenotype during 5 years of follow-up. The event rate was low and only two patients had a near-fatal arrhythmic event, both after developing a phenotype. This information could guide management of phenotype-negative patients with CPVT.

PO-04-143 CARDIOVASCULAR OUTCOMES IN LMNA-MEDIATED CARDIAC LAMINOPATHY: THE MAYO CLINIC EXPERIENCE

Pathogenic loss-of-function variants in LMNA-encoding lamin A/C cause a range of phenotypes, including lipodystrophy, premature aging, muscular dystrophy, and cardiomyopathy. LMNA-mediated cardiac laminopathy is viewed as a particularly malignant form of arrhythmogenic dilated cardiomyopathy (DCM). However, a paucity of data exists comparing the cardiovascular outcomes in cardiac laminopathy to other DCM genotypes. Therefore, we sought to ascertain whether the prevalence of advanced heart failure (AHF), ventricular arrhythmia (VA), and stroke events differ between patients with either LMNA-mediated DCM or TTN-mediated DCM who were evaluated in a single tertiary medical center. All patients with either a pathogenic (P) or likely pathogenic (LP) variant in either LMNA or TTN in the Mayo Clinic Genetic ACM Registry (n=389) were included. A VA event was defined as sudden cardiac death (SCD), sudden cardiac arrest (SCA), sustained VA, or an appropriate ICD shock while an AHF event was defined as ventricular assist device implantation or heart transplantation. Overall, 88 patients with a P/LP variant in LMNA (61% female) and 72 patients with a P/LP variant in TTN (42% female) were identified. LMNA-positive patients were more likely to have a family history of SCA/SCD (56% vs 35%; p=0.008) and more likely to receive an ICD (60% versus 33%; p=0.001). Interestingly, the prevalence of atrial fibrillation (51% vs. 40%; p=0.2), stroke (8% vs. 8%; p=0.9), and AHF events (12% vs 8%; p=0.4) was similar between LMNA- and TTN-positive patients. However, LMNA-positive patients trended towards more VA events (32% vs 20%; p=0.08). Independent of sex, time-to-event analysis showed LMNA patients had an earlier time (p=0.0009) to a composite endpoint (AHF event or VA event) and remained significant when separating the endpoints: AHF event (p=0.008) and VA event (p=0.0009). LMNA-mediated cardiac laminopathy is a highly arrhythmogenic form of DCM with nearly one-third experiencing a SCA and/or appropriate ICD therapy and half with a history of atrial fibrillation. Although the overall rate of ventricular arrhythmic and AHF events was similar between LMNA and TTN P/LP variant-positive patients, cardiac laminopathy results in earlier end stage heart failure and potentially lethal ventricular arrhythmias.

Prevalence, characteristics, and natural history of apical phenotype in a large cohort of patients with hypertrophic cardiomyopathy

BackgroundApical hypertrophic cardiomyopathy (ApHCM) is a variant of hypertrophic cardiomyopathy (HCM) with distinct imaging and clinical characteristics. Data on the prognosis of this HCM subgroup appear conflicting. Our study aims to clarify the natural history of ApHCM and identify predictors of outcomes. Materials and methodsA total of 856 patients with HCM were retrospectively examined. ApHCM was defined as asymmetric left ventricular hypertrophy confined predominantly at the apex, either isolated (pure ApHCM type) or with co-existent hypertrophy of the interventricular septum (mixed ApHCM). Echocardiographic, clinical, and survival data were compared between individuals with ApHCM and non-ApHCM. ResultsA total of 143 (16.7%) patients were diagnosed with ApHCM. Compared with non-ApHCM, subjects with apical HCM were diagnosed at an older age and had better echocardiographic indices and more comorbidities at baseline. Apical aneurysms were more prevalent among the ApHCM phenotype (6.3% vs. 1.7%, p = 0.003). During a mean follow-up of 6 ± 3 years, ApHCM was characterized by lower all-cause, cardiovascular, heart failure-related mortality, and ventricular arrhythmic events compared with non-ApHCM. Multivariate analysis identified atrial fibrillation and HCM risk-sudden cardiac death (SCD) as independent predictors of the composite outcome of overall mortality and hospitalizations for cardiovascular reasons (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.9-9.5 for atrial fibrillation and HR 1.2, 95% CI 1.02-1.3 for HCM risk-SCD) in ApHCM. ConclusionsApHCM exhibited a lower rate of all-cause mortality and arrhythmic events in the middle-aged population of patients with HCM. Atrial fibrillation and HCM risk-sudden cardiac death were independent predictors of a composite of overall mortality and cardiovascular hospitalizations among those with ApHCM.

310 CLINICAL COURSE AND CHARACTERISTICS OF ADVANCED HEART FAILURE ASSOCIATED WITH ARRHYTHMOGENIC CARDIOMYOPATHY

Abstract Background The prevalence and course of heart failure (HF) in arrhythmogenic cardiomyopathy (ACM) is unresolved, and previous studies have mostly focused on the right-dominant variant of the disease, less prone to HF. Conversely, ACM variants with left ventricular (LV) involvement are now increasingly recognized, often initially ‘mis-diagnosed’ as dilated cardiomyopathy. Aim of this study was therefore to describe the prevalence and clinical course of advance HF in the full clinical spectrum of ACM. Methods We retrospectively reviewed records of all ACM patients diagnosed before 2021 from 3 Italian Cardiomyopathy Referral Centres (Azienda Ospedaliero Universitaria Careggi; Policlinico Sant’Orsola; Azienda Ospedaliero Universitaria Sant’Andrea). LV involvement was diagnosed in the presence of subepicardial late gadolinium enhancement (LGE) in at least 3 contiguous segments in the same short-axis slice at cardiac magnetic resonance, independent of whether it fulfilled the 2010 Task Force criteria for right-dominant ACM (biventricular ACM) or not (left-dominant ACM); in this latter case, diagnosis was reached after careful exclusion of other differential diagnosis, and only when at least one of the following features was present: likely pathogenic/pathogenic genetic variant associated with ACM; familial history of ACM; electrocardiographic abnormalities suggestive of ACM with LV involvement. Advanced HF was defined as NYHA functional class III/IV and/or referral for heart transplantation. Median follow-up was 6 years. Results Forty-four out of 174 ACM patients (25%) developed advanced HF: 10 right-dominant ACM and 34 with LV involvement. Twenty ACM patients were initially diagnosed with dilated cardiomyopathy; as such, development of advanced HF in 17 cases preceded the diagnosis of ACM. Five patients were diagnosed with ACM after heart transplantation, by histological examination. In the other 22, median time from ACM diagnosis to advanced HF development was 4 years. As compared to those without, advanced HF patients were more likely to present LV involvement. During clinical course, 20 (46%) advanced HF patients received at least one appropriate ICD intervention, with 13 experiencing an electrical storm. Twenty-six (59%) patients required HF-related hospitalization, and 32 (72%) were referred for heart transplantation with 25 ultimately receiving it. ACM patients with advanced HF, compared to those without, experienced a higher rate of mortality (36% vs. 6%; OR 3.5 [95%CI: 1.4-8.7], p=0.01) and ventricular arrhythmic events (41% vs. 11%; OR 2.4 [95%CI: 1.1-5.0], p=0.02). Conclusions Advanced HF progression in ACM is not rare, and occurs more frequently in variants with LV involvement. Advanced HF is associated with increased mortality and arrhythmic risk.

Hybrid-Approach Ablation in Drug-Refractory Arrhythmogenic Right Ventricular Cardiomyopathy

Management of ventricular arrhythmias (VAs) beyond implantable cardioverter-defibrillator positioning in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is challenging. Catheter ablation of the ventricular substrate often requires a combination of endocardial and epicardial approaches, with disappointing outcomes due to the progressive nature of the disease. We report the Universitair Ziekenhuis Brussel experience through a case series of 16 patients with drug-refractory ARVC, who have undergone endocardial and/or epicardial catheter ablation of VAs with a thoracoscopic hybrid-approach. After a mean follow-up time of 5.16 years (SD 2.9 years) from the first hybrid-approach ablation, VA recurrence was observed in 5 patients (31.25%): among these, patients 4 patients (80%) received a previous ablation and 1 of 11 patients (9.09%) who had a hybrid ablation as first approach had a VA recurrence (80% vs 9.09%; log-rank p=0.04). Despite the recurrence rate of arrhythmic events, all patients had a significant reduction in the arrhythmic burden after ablation, with a mean of 4.65 years (SD 2.9 years) of freedom from clinically significant arrhythmias, defined as symptomatic VAs or implantable cardioverter-defibrillator-delivered therapies. In conclusion, our case series confirms that management of VAs in patients with ARVC is difficult because patients do not always respond to antiarrhythmic medications and can require multiple invasive procedures. A multidisciplinary approach involving cardiologists, cardiac surgeons, and cardiac electrophysiologists, together with recent cardiac mapping techniques and ablation tools, might mitigate these difficulties and improve outcomes.

Diagnostic evaluation of implantable loop recorder devices associated with remote monitoring: a retrospective multicentric study

Abstract Funding Acknowledgements Type of funding sources: None. It has been proven that Implantable Loop Recorders (ILRs) and remote monitoring could improve diagnostic rate, shorten time-to-diagnosis and thus better patient’s clinical outcome. Medical indications to ILRs have been lately extended, and many technical improvements have been achieved in the last few years. Nowadays many different ILRs are available, therefore choosing the best device, according to the patient’s clinical features, could help to reach an optimal patient management. Aim of this retrospective multicentric study is to compare which is best between 2nd generation ILR Medtronic Reveal™ LINQ (MRL) or St. Jude Medical Confirm™ RX (SCX), both associated with remote monitoring, in terms of overall accuracy rate (OAR), true positive detection rate (TPDR) and arrhythmias-free survival (AFS). Patients included in the study required an ILR implant for syncope, non-recurring heartbeat, suspect AF, Brugada Syndrome, post-ablation AF monitoring and non-stustained ventricular tachycardia. Medtronic Reveal™ LINQ (n=436, mean age 66±15, mean BMI 30±5) and St. Jude Medical Confirm™ RX (n=98, mean age 64±14, BMI 27.5±4) implanted patients underwent a weekly remote and a six-monthly outpatient follow-up. Every transmission was judged by two different cardiologists. The final diagnosis was set only in case of agreement, conversely, the transmission was discussed either considered non-diagnostic. Patients were studied for atrial fibrillation (AF), pauses (Ps), bradycardias (Bs) and tachycardias (Ts). MRL transmitted 5585 times, SCX 7545 (monthly transmission/patient ratio 25.5±45.6 vs 0.9±1.1 respectively). MRL had statistically significant better OAR for AF (61% vs 14%, p&amp;lt;0,001), Ps (20% vs 7%, p&amp;lt;0.001) and Bs (72% vs 20%, p&amp;lt;0.001). SCX had statistically better OAR for Ts (84% vs 56%, p&amp;lt;0.001). MRL had statistically significant better TPDR for AF alone (82% vs 48%, p&amp;lt;0.001) and non-statistically significant better TPDR for Ps (32% vs 28%, p=0.117), Bs (48% vs 38%, p=0.133) and Ts (69% vs 69%, p=0.505). Patient with MRL had better AFS at a six-months follow-up (72% vs 20%, p&amp;lt;0.001). The overall accuracy rate for every arrhythmic episode was better in MRL implanted patients than in the SCX implanted ones (43% vs 16%, p=0.001). Transmission rate was higher in SCX, even though MRL had a better accuracy in detecting real arrhythmic events. The overall accuracy rate of arrhythmic events in both groups is sub-optimal, therefore further engineering research is required to improve diagnostic accuracy of ILRs.

Impact of Successful Chronic Coronary Total Occlusion Recanalization on Recurrence of Ventricular Arrhythmias in Implantable Cardioverter-Defibrillator Recipients for Ischemic Cardiomyopathy (VACTO PCI Study)

BackgroundCoronary chronic total occlusion lesions (CTOs) confer an increased risk of arrhythmic events among patients with ischemic cardiomyopathy (ICM) and implantable cardioverter-defibrillator (ICD) carriers, however the impact of CTO recanalization in this population remains unassessed. AimsEvaluate the impact of CTOs percutaneous coronary interventions (PCI) on arrhythmic events. MethodsPatients with ICM and ICD from the VACTO I-II registries: patients with medically treated CTO (CTO-OMT group) and without CTO (no-CTO group) were compared after inverse-probability-weighting adjustment (IPWT) with a similar population of consecutive patients undergoing CTO-PCI. The primary endpoint was appropriate ICD therapy. The secondary endpoint was all-cause mortality. ResultsThe total of 622 patients (mean age 67 ± 10 years, mean left ventricular ejection fraction 36 ± 11%) included in the analysis was composed by: CTO-PCI patients n = 113, CTO-OMT patients n = 286, no-CTO patients n = 223. In the CTO-PCI group, compared to the CTO-OMT group, 5-year Kaplan Meier estimates for appropriate ICD therapy (20.4% vs. 56.4%, IPW-adjusted HR: 0.45, 95% CI 0.29–0.71) and mortality (8.8% vs. 23%, IPW-adjusted HR: 0.43, 95% CI 0.22–0.85) were lower, driven by infarct related artery CTO (IRA-CTO) PCI, while similar to those occurring in the no-CTO group. ConclusionsIn this large population, those with CTO receiving PCI had lower arrhythmic event rates and lower mortality compared to the CTO-OMT group, while showing an event rate similar to no-CTO patients. Sensitivity analyses suggest that the beneficial effect on the arrhythmic outcome was driven by IRA-CTO revascularization. ClassificationChronic total occlusion.

161 Biosensor in cardiology. T-care project: a preliminary study on innovative wearable non-invasive telemonitoring system

Abstract The demographic trend evolution and the modification of health needs highlight the requirement for a novel organization of the healthcare system. Telemedicine is a technological tool that allows a knockdown of geographic barriers being useful in the management of remote patient assistance. Telemedicine is roughly applied in different cardiology’s areas, from telemetric to implantable devices (loop recorders) in order to monitor cardiac rate, cardiac rhythm variations, and the onset of arrhythmic events. The aim of the present study is to assess the validity of wearable devices (T-shirt equipped with biosensors and bands with photopletimographic system) in monitoring EKG, cardiac rate, and pulse oximetry. We enrolled 38 patients, 25 of whom admitted to the Cardiology Unit, University of Bari. Main characteristics of the sample are listed in Table 1. The difference between traditional monitoring system and wearable biosensors in not statistically significant as shown in Figure 1; therefore the devices tested in this study show a satisfying level of reliability in monitoring cardiac rate, pulse oximetry, QT interval, QRS complexes, and onset of arrhythmic events. However, alerts produced by arrhythmias different from atrial fibrillation are not completely reliable; moreover, the software and the diagnostic algorithm need to be optimized for motion artefacts. For these reasons, results need to be reproduced on a large cohort of patients.

Strain echocardiography improves prediction of arrhythmic events in ischemic and non-ischemic dilated cardiomyopathy

BackgroundRecent evidence suggests that an implantable cardioverter defibrillator (ICD) in non-ischemic cardiomyopathy (NICM) may not offer mortality benefit. We aimed to investigate if etiology of heart failure and strain echocardiography can improve risk stratification of life threatening ventricular arrhythmia (VA) in heart failure patients. MethodsThis prospective multi-center follow-up study consecutively included NICM and ischemic cardiomyopathy (ICM) patients with left ventricular ejection fraction (LVEF) <40%. We assessed LVEF, global longitudinal strain (GLS) and mechanical dispersion (MD) by echocardiography. Ventricular arrhythmia was defined as sustained ventricular tachycardia, sudden cardiac death or appropriate shock from an ICD. ResultsWe included 290 patients (67 ± 13 years old, 74% males, 207(71%) ICM). During 22 ± 12 months follow up, VA occurred in 32(11%) patients. MD and GLS were both markers of VA in patients with ICM and NICM, whereas LVEF was not (p = 0.14). MD independently predicted VA (HR: 1.19; 95% CI 1.08–1.32, p = 0.001), with excellent arrhythmia free survival in patients with MD <70 ms (Log rank p < 0.001). Patients with NICM and MD <70 ms had the lowest VA incidence with an event rate of 3%/year, while patients with ICM and MD >70 ms had highest VA incidence with an event rate of 16%/year. ConclusionPatients with NICM and normal MD had low arrhythmic event rate, comparable to the general population. Patients with ICM and MD >70 ms had the highest risk of VA. Combining heart failure etiology and strain echocardiography may classify heart failure patients in low, intermediate and high risk of VA and thereby aid ICD decision strategies.

Incremental Value of an Insertable Cardiac Monitor in Patients with Hypertrophic Cardiomyopathy with Low or Intermediate Risk for Sudden Cardiac Death

Aims: The aim of the present study was to compare the rate of actionable arrhythmic events between patients with hypertrophic cardiomyopathy (HCM) who are monitored with an insertable cardiac monitor (ICM) or Holter monitoring. Methods: We studied 50 patients (mean age 52 years, 72% men) with HCM at low or intermediate risk for sudden cardiac death (SCD), of whom 25 patients received an ICM between November 2014 and February 2019. We retrospectively identified a control group of 25 patients who were matched on age, sex, and HCM Risk-SCD score category. The mean HCM Risk-SCD score was 3.41 ± 1.31 and 3.31 ± 1.43 for the ICM and Holter groups, respectively. The primary endpoint was an actionable event which was defined as an arrhythmic event resulting in a change in patient management. The secondary endpoint was the occurrence of ventricular tachycardia (VT). Results: The cumulative actionable event rate at 30 months was higher in the ICM group (51 vs. 27%, log-rank p value <0.01). De novo atrial fibrillation requiring oral anticoagulation occurred only in the ICM group (n = 3). Overall, 4 implantable cardioverter-defibrillators were implanted for primary prevention (n = 2 in each group). The cumulative rate of VT episodes at 30 months was similar between groups (23% [ICM group] vs. 42% [Holter group], log-rank p value = 0.71). Furthermore, the characteristics of VT were similar between groups with regard to the number of beats and rate. Conclusions: In adults with HCM, an ICM will detect more arrhythmic events requiring an intervention than a conventional Holter strategy. In contrast, the diagnostic yield of detecting VT seems similar for both groups.

Right bundle brunch block in patients with acute myocardial infarction is associated with a higher in-hospital arrhythmic risk and mortality, and a worse prognosis after discharge

IntroductionRecently, the presence of right bundle brunch block (RBBB) in patients with persistent ischaemic symptoms has been suggested as an indication for emergent coronary angiography. ObjectiveThe aim of this study was to assess the prognostic impact of RBBB in patients with acute myocardial infarction (AMI) before the implementation of the recent recommendations. MethodsWe retrospectively studied consecutive patients admitted with AMI between 2011 and 2013. Patients with left bundle brunch block, pacemaker, or nonspecific intraventricular conduction delay were excluded. Patients with RBBB were compared with those without RBBB. Clinical characteristics, in-hospital evolution, and major adverse cardiovascular events (MACE) during follow-up, defined as cardiovascular death, sustained ventricular arrhythmias, acute heart failure syndromes, recurrent myocardial infarction, or acute stroke, were analysed. ResultsThe analysis included 481 patients. Thirty two patients (6.7%) had RBBB. Patients with RBBB were older. During hospital admission, RBBB patients had a higher rate of sustained ventricular tachycardia and death. Survival curve analysis showed that patients with RBBB had a lower in-hospital survival rate (Log-rank, p = 0.004). After discharge, during a mean follow-up time of 24.3 ± 11.6 months, 53 patients (12%) died. Survival curve analysis showed a lower survival rate free of MACE for those patients with RBBB (Log-rank, p = 0.011). RBBB was independently associated with MACE occurrence (HR 2.17, 95% CI 1.07–4.43; p = 0.033), after adjusting for demographic data, coronary angiography findings, treatment performed, echocardiographic evaluation, and medical therapy. ConclusionPatients with RBBB had a higher rate of in-hospital mortality and arrhythmic events, and an increased risk of MACE during follow-up.

Arrhythmia Burden in Patients with Indolent Lymphoma

Introduction Indolent Non-Hodgkin lymphomas (NHL) comprise a heterogeneous group of diseases including marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma (LPL), small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), and follicular lymphoma (FL). These compose a heterogenous group of disorders that frequently measures survival in years due to the long natural history of these diseases. Frequency and morbidity of cardiac arrhythmias in patients with indolent lymphoma is unknown, but recent observations note that arrhythmias are an increasing problem. Due to advances in treatment for indolent NHL with emergence of novel therapeutics, combined with an aging population and a long natural history, understanding of arrhythmia burden in indolent lymphoma is an area of research with important implications for patients undergoing active treatment as well as for long term lymphoma survivors. Methods Adult patients 18 years or older with indolent NHL treated at the University of Rochester Wilmot Cancer Institute between 2013-2019 were included in the Cardio-Oncology Lymphoid Malignancies Database and analyzed. The primary objective of this study was to define the rate of arrhythmic events and sudden cardiac death in patients with indolent lymphoma during treatment. Cardiac arrhythmias including ventricular arrhythmias (VT/VF), atrial arrhythmias (atrial fibrillation (afib), flutter, SVT and atrial tachycardia), and bradyarrhythmias were identified using ICD-10 codes. Kaplan-Meier survival analysis was used to assess cumulative probability of arrhythmia. Results There were nine hundred and eighteen patients who were diagnosed with indolent lymphoma. Diagnoses included: CLL, N=414; FL, N=284; MZL, N=144; LPL, N=76. Median age was 64, and 43% were female. There were 383 (42%) patients who received treatment. Treatments were classified as chemotherapy, targeted therapy, monoclonal antibodies/immunotherapy, and combination therapy. There were no significant differences in baseline characteristics between treated and never treated patients. At the time of diagnosis, 277 patients (30%) had hypertension, 101 (11%) had prior history of arrhythmia. During median follow up of 24 months, 168 patients (18%) developed a new or recurrent arrhythmia based on ICD-10 codes documented in the electronic medical record. Sixty-three out of one hundred sixty-eight patients had both prior history of and recurrence of arrhythmia, while one hundred five had a new diagnosis of arrhythmia. Afib was the most common arrhythmia, noted in 81 patients (9%). At 6 months from diagnosis, cumulative probability of developing any arrhythmia was 8% (Figure 1). Of all arrhythmias, 89/168 (53%) occurred in SLL/CLL, 35/168 (21%) in FL, 17/168 (10%) in LPL, 27/168 (16%) in MZL. Arrhythmias on treatment occurred in 4/95 patients receiving chemotherapy alone (4.2%), 12/95 patients receiving monoclonal antibodies/immunotherapy (12.6%), and 28/95 patients receiving targeted therapy (29.4%). Most arrhythmias (51/95; 53.6%) occurred in patients receiving combination therapy (chemoimmunotherapy or targeted/immunotherapy). Overall, there were 80 (9%) deaths. Ten deaths were related to cardiovascular diseases; of which 8/10 (80%) were from sudden cardiac death. Conclusions This real-world cohort demonstrates that patients with indolent lymphoma could have an increased risk of cardiac arrhythmias that is increased by treatment. Afib was the most common arrhythmia identified in this study and appears increased compared to the incidence in the general age matched population (1-1.8 per 100 person-years). Surprisingly, of 80 deaths, 8 (10%) were attributed to sudden cardiac death. This data set contributes important information that can help identify patients at increased risk of cardiovascular morbidity and mortality that can impact treatment. Prospective monitoring in these patients may better define the incidence and associated risks of arrhythmias. Future directions will focus on risk factors for arrhythmias and developing an approach to prevent and treat arrhythmias in this patient population. Updated results will be presented at the meeting. Disclosures Zent: Acerta / Astra Zeneca: Research Funding; TG Therapeutics, Inc: Research Funding; Mentrik Biotech: Research Funding. Barr:Janssen: Consultancy; Abbvie/Pharmacyclics: Consultancy, Research Funding; Verastem: Consultancy; Celgene: Consultancy; Seattle Genetics: Consultancy; TG therapeutics: Consultancy, Research Funding; Morphosys: Consultancy; Gilead: Consultancy; AstraZeneca: Consultancy, Research Funding; Merck: Consultancy; Genentech: Consultancy. Reagan:Kite, a Gilead Company: Consultancy; Seattle Genetics: Research Funding; Curis: Consultancy. Friedberg:Seattle Genetics: Research Funding; Roche: Other: Travel expenses; Bayer: Consultancy; Astellas: Consultancy; Acerta Pharma - A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Kite Pharmaceuticals: Research Funding; Portola Pharmaceuticals: Consultancy.

Prognostic value of non-ischemic ring-like left ventricular scar pattern in patients with apparently idiopathic ventricular arrhythmias: a CMR imaging study

Abstract Background The presence of left ventricular (LV) late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) has been correlated to life-threatening arrhythmic events in patients with apparently idiopathic ventricular arrhythmias (VAs). Aim of the present study was to investigate the prognostic significance of a specific LV-LGE phenotype characterized by a subepicardial/midmyocardial “ring-like” pattern of fibrosis. Methods Out of a total of 518 consecutive patients with apparently idiopathic VAs who underwent CMR study, 79 (15%) had evidence of LV-LGE. Of these, 23 (4%) patients had LV LGE with ring-like pattern, defined as subepicardial or midmyocardial LGE involving at least 3 contiguous segments in the same slice (group A), while 56 (11%) patients had LV LGE with no ring-like pattern (group B). The remaining 439 patients had no LGE (group C). The end-point of the study was a composite SCD, resuscitated cardiac arrest and nonfatal episodes of ventricular fibrillation or documented sustained ventricular tachycardia. Results Group A patients were more frequently males compared to groups B and C (96% vs. 79% vs. 52%; p&amp;lt;0.01) and had more frequently a family history of SCD and/or cardiomyopathy (30% vs. 11% vs. 5%; p&amp;lt;0.01). All patients in Group A showed VAs with a predominant RBBB morphology vs. 38 (68%) patients in Group B and 65 (15%) in Group C (p&amp;lt;0.01). During a follow-up of 63±39 months, the composite outcome occurred in 13 patients (57%) in Group A vs. 11 (20%) in Group B and 2 (1%) in Group C (p&amp;lt;0.01). Conclusion In patients with apparently idiopathic VAs, a nonischemic LV-LGE with a ring-like pattern at CMR is associated with a high rate of malignant arrhythmic events during follow-up. Funding Acknowledgement Type of funding source: None

Risk of arrhythmic events after alcohol septal ablation for hypertrophic cardiomyopathy using continuous implantable cardiac monitoring

Alcohol septal ablation (ASA) in patients with hypertrophic cardiomyopathy (HCM) can lead to heart rhythm disturbances including complete heart block (CHB) and atrial and ventricular arrhythmias. We aimed to evaluate the utility of long-term arrhythmia monitoring with an implantable cardiac monitor (ICM) after ASA. Between February 2014 and March 2019, 56 patients with HCM undergoing ASA were enrolled in a prospective study and underwent ICM implantation. Kaplan-Meier survival analysis was used to assess the rate of ICM-detected arrhythmic events. The mean age was 59 ± 11 years, and 20 (36%) were women. The median (25th, 75th percentile) resting left ventricular outflow tract gradient obtained by echocardiography was 43 (22, 81) mm Hg. Greater than 1 septal perforating artery was injected in 48 patients (86%). The Kaplan-Meier cumulative rate of ICM-detected arrhythmic events at 18 months of follow-up was 71%, with an event rate of 43% occurring within 3 months of ASA. The cumulative rate of the ICM-detected first atrial fibrillation event at 18 months was 37%, and the corresponding rate of CHB was 19%. All atrial fibrillation and CHB events were actionable, leading to the initiation of anticoagulation and pacemaker implantation, respectively. No baseline demographic or procedural variables were identified as independent predictors of an increased risk of developing ICM-detected arrhythmic events. After ASA, ICM is effective in capturing clinically actionable arrhythmic events in patients with HCM regardless of patient's baseline risk factors.