History Of Ventricular Arrhythmias Research Articles

Novel electric predictors of lethal arrhythmic event in patients with hypertrophic cardiomyopathy

Abstract Background Little is known regarding the association between electrical markers and lethal arrhythmic events (LAE) in patients with hypertrophic cardiomyopathy (HCM). This study aimed to identify the electrical predictors of LAE in adult patients with HCM. Methods This study was a retrospective analysis of patients with HCM at a single center from 1998 to 2021. LAE was defined as a composite outcome of (1) sustained ventricular arrhythmia, (2) aborted sudden cardiac death (SCD), (3) implantable cardioverter defibrillator (ICD) implantation, and (4) appropriate ICD shock. A 12-lead electrocardiography was performed at the time of diagnosis. Results A total of 611 patients with HCM were analyzed, and 48 (7.8%) experienced LAE. Patients who experienced LAE were diagnosed at a younger age and more frequently had history of ventricular arrhythmia, new-onset atrial fibrillation (AF) or non-sustained ventricular tachycardia. New-onset AF, an increase in the QTc interval, and the absence of massive LVH were associated with LAE risk. In addition to conventional markers of HCM Risk-SCD, consideration of the QTc interval and massive LVH on electrocardiography improved the prediction of LAE (area under curve 0.682 to 0.740). Further inclusion of new-onset AF, history of ventricular arrhythmia, HCM type, and left ventricular mass index improved the predictability to 0.867. Conclusion An increase in the QTc interval, the absence of a massive LVH pattern on electrocardiography (ECG), and new-onset AF were independently associated with an increased risk of LAE. Comprehensive stratification using electrical markers improves the prediction of LAE when combined with conventional markers.

Exercise-induced regional heterogeneity of myocardial left ventricular contraction in hereditary long QT syndrome

Abstract Background Hereditary long QT syndrome (LQTS) is characterized by prolonged ventricular repolarization and an increased risk for ventricular arrhythmias (VA) and sudden cardiac death. Dispersion of ventricular repolarization in LQTS may be more pronounced during exercise and not only impacts the heart’s electrical functions but also the pattern of mechanical contraction. Little is known about the intraventricular heterogeneity of wall motion abnormalities in LQTS patients. Methods In this cross-sectional study we quantify regional, transmural, and longitudinal alterations in left ventricular (LV) contraction at rest, during exercise, and recovery in genetically confirmed LQTS patients and healthy controls to evaluate their value in differentiating high risk patients as defined by a history of VA. ECG and echocardiographic assessments were conducted during rest, peak ergometer activity (105 to 125 bpm), and four minutes into recovery phases. Longitudinal strain (LStr) parameters were measured for each LV segment separately. We differentiated LStr variations as heterogeneity of LStr amplitude (hetLStr; standard deviation [SD] or mean range) and dispersion of time-to-peak LStr (disLStr; SD or mean range). Here, we present the analyses of disLStr. Results At present, 15 patients with genetically confirmed LQTS (LQT1: 8, LQTS 2: 7; mean QTc 475 ± 46 ms) have been included of which 9 had a history of VA. In addition, we collected data from 8 age- and gender-matched control patients (mean QTc 401 ± 18 ms). LV ejection fraction and LStr were not significantly different between the LQTS and control groups. However, LQTS patients exhibited a significantly lower mean LStr in both the endocardial and epicardial layers across all phases compared to control. We observed a significantly more pronounced disLStr across all segments in the LQTS group during the rest and recovery phases in the endocardial layer and during all phases in the epicardial layer. Regional differences (apical vs. basal) were found in all LQTS patients only endocardially at rest. Globally, disLStr showed transmural differences (epicardial vs. endocardial) in both asymptomatic and symptomatic LQTS patients during peak exercise and recovery. Upon segmental analysis, it was observed that symptomatic patients exhibited these transmural differences apically already at rest (p=.004), as well as in the basal region during peak exercise (p=.01), and in the apical region during recovery (p=.02). Conclusion LQTS patients show regional (base to apex) and transmural (endocardial to epicardial) heterogeneities in myocardial contraction at rest, during exercise, and recovery as compared to healthy patients. These regional variations in myocardial contraction patterns may be more pronounced in high risk LQTS patients. Ongoing analyses of hetLStr are in progress to corroborate our findings.

The Role of Postoperative Magnesium Infusion in Minimizing Ventricular Arrhythmia Risk after Cardiopulmonary Bypass

Introduction: Cardiopulmonary bypass increases the incidence of postoperative ventricular arrhythmias in cardiac surgery. Magnesium, which is essential for cardiac function and may prevent arrhythmias, is frequently reduced after cardiac surgery. Aim of the Study: This study aimed to investigate the preventive effects of magnesium infusion in reducing the occurrence of ventricular arrhythmias in individuals who have undergone cardiopulmonary bypass. Methods: This study, done at Bangabandhu Sheikh Mujib Medical University, Dhaka, from July 2020 to June 2022, involved 120 participants in two groups: one received magnesium sulfate following standard cardiopulmonary bypass surgery (Group A), and the other did not (Group B). Both groups were monitored in the ICU with continuous ECG tracking and assessed for ventricular arrhythmias postoperatively on days 0–3. The inclusion criteria comprised adult cardiac patients in preoperative sinus rhythm with normal magnesium levels, excluding those with a history of ventricular arrhythmias or specific medical conditions. Data collected through a questionnaire, interviews, and medical records were analyzed using SPSS version 26. Result: The mean age of the patients in Group A was 53.83±14.54 years and in Group B was 54.50 ± 10.50 years. The mean difference in postoperative Mg++ was statistically significant (p<0.05) in POD 0, POD 1, POD 2, and POD 3. In this study, there were more VA-positive patients in Group B than in Group A; 16.67% had positive ventricular arrhythmia (PVC 8.3%, VT 3.33%, VF 5.00%), while 83.33% were negative VA. Group B had 66.67% negative VA and 33.33% positive VA (PVC 15.00%, VT 10.00%, VF 8.33%). Conclusion: This study identified that the postoperative Mg infusion after cardio pulmonary bypass reduces the incidence of postoperative arrhythmias in cardiac patients. Based on the findings, we recommend using intravenous magnesium as an alternative to prevent ventricular arrhythmias after CPB in cardiac patients.

Characteristics and incidence of cardiac events across spectrum of age in cardiac sarcoidosis

BackgroundClinical characteristics and the risk of cardiovascular events in patients with cardiac sarcoidosis (CS) according to the age of initial diagnosis are unclear. MethodsThis study is a sub-analysis of the ILLUMINATE-CS registry, which is a retrospective, multicenter registry that enrolled patients with CS between 2001 and 2017. Patients were divided into three groups according to the tertile of age at the time of initial diagnosis of CS. The study compared the clinical background at the time of CS diagnosis and the incidence rate of cardiac events across age categories. ResultsA total of 511 patients were analyzed in this study. In baseline, older patients were more likely to be female. History of hypertension, heart failure admission, and atrioventricular block were more common in patients with older age. There was no significant difference in the history of ventricular arrhythmias and left ventricular ejection fraction among all age groups. During a median follow-up period of 3.2 [IQR: 1.7–4.2] years, 35 deaths, 56 heart failure hospitalization, and 98 fatal ventricular arrhythmias was observed. The incidence rate of all-cause death and heart failure hospitalization was significantly higher in patients with older age (p < 0.001), while there was no significant difference in the incidence rate of ventricular arrhythmia among age groups (p = 0.74). ConclusionsIn patients with CS, the risk of all-cause death and heart failure hospitalization was higher in older patients compared with other age groups; however, the risk of ventricular arrhythmia was comparable across all age groups.

Optimal left ventricular ejection fraction in risk stratification of patients with cardiac sarcoidosis.

Identifying patients with cardiac sarcoidosis (CS) who are at an increased risk of sudden cardiac death (SCD) poses a clinical challenge. We sought to identify the optimal cutoff for left ventricular ejection fraction (LVEF) in predicting ventricular arrhythmia (VA) and all-cause mortality and to identify clinical and imaging risk factors in patients with known CS. This retrospective cohort included 273 patients with well-established CS. The primary endpoint was a composite of VA and all-cause mortality. A modified receiver operating curve analysis was utilized to identify the optimal cutoff for LVEF in predicting the primary composite endpoint. Cox proportional hazard regression analysis was used to identify independent risk factors of the outcomes. At median follow-up of 7.9 years, the rate of the primary endpoint was 38% (83 VAs and 32 all-cause deaths). The 5-year overall survival rate was 97%. The optimal cutoff LVEF for the primary composite endpoint was 42% in the entire cohort and in subjects without a history of VA. Younger age, history of VA, lower LVEF, and any presence of scar by cardiac magnetic resonance (CMR) imaging and/or positron emission tomography (PET) were found to be independent risk factors for the primary endpoint and for VA, whereas lower LVEF, baseline NT-proBNP, and any presence of scar were independent risk factor of all-cause mortality. Among patients with CS, a mild reduction in LVEF of 42% was identified as the optimal cutoff for predicting VA and all-cause mortality. Prior VA and scar by CMR or PET are strong risk factors for future VA and all-cause mortality.

A unified framework for multi-lead ECG characterization using Laplacian Eigenmaps

Background. The analysis of multi-lead electrocardiographic (ECG) signals requires integrating the information derived from each lead to reach clinically relevant conclusions. This analysis could benefit from data-driven methods compacting the information in those leads into lower-dimensional representations (i.e. 2 or 3 dimensions instead of 12). Objective. We propose Laplacian Eigenmaps (LE) to create a unified framework where ECGs from different subjects can be compared and their abnormalities are enhanced. Approach. We conceive a normal reference ECG space based on LE, calculated using signals of healthy subjects in sinus rhythm. Signals from new subjects can be mapped onto this reference space creating a loop per heartbeat that captures ECG abnormalities. A set of parameters, based on distance metrics and on the shape of loops, are proposed to quantify the differences between subjects. Main results. This methodology was applied to find structural and arrhythmogenic changes in the ECG. The LE framework consistently captured the characteristics of healthy ECGs, confirming that normal signals behaved similarly in the LE space. Significant differences between normal signals, and those from patients with ischemic heart disease or dilated cardiomyopathy were detected. In contrast, LE biomarkers did not identify differences between patients with cardiomyopathy and a history of ventricular arrhythmia and their matched controls. Significance. This LE unified framework offers a new representation of multi-lead signals, reducing dimensionality while enhancing imperceptible abnormalities and enabling the comparison of signals of different subjects.

Leucocyte-derived micro-RNAs as candidate biomarkers in Brugada syndrome.

Risk stratification for sudden cardiac death in patients with Brugada syndrome remains a major challenge. Contemporary risk prediction models have only modest predictive value. The aim of this study was to assess the role of micro-RNAs from peripheral blood as candidate biomarkers in Brugada syndrome. In this prospective study, Brugada patients and unaffected control individuals were enrolled for analysis of leucocyte-derived microRNAs (miRNAs) levels. Expression levels of 798 different circulating miRNAs were analysed on the NanoString® nCounter platform. All results were cross-validated by using a quantitative polymerase chain reaction. Micro-RNA expression levels of Brugada patients were compared with clinical data. A total of 21 definite Brugada patients (38% with a history of ventricular arrhythmia or cardiac arrest) and 30 unaffected control individuals were included in the study. Micro-RNA analysis showed a distinct expression profile in Brugada patients with 42 differentially expressed markers (38 up-regulated, 4 down-regulated miRNAs). The symptom status of Brugada patients was associated with a distinct miRNA signature. Micro-RNAs 145-5p and 585-3p were significantly up-regulated in symptomatic Brugada patients (P = 0.04). Incorporating miRNAs 145-5p and 585-3p into a multivariable model demonstrated significantly increased symptom prediction (area under the curve = 0.96; 95% confidence interval: 0.88-1.00). Brugada patients display a distinct miRNA expression profile compared with unaffected control individuals. There is also evidence that certain miRNAs (miR-145-5p and miR-585-3p) are associated with the symptom status of Brugada patients. The results suggest the principal utility of leucocyte-derived miRNAs as prognostic biomarkers for Brugada syndrome.

PO-02-010 CRT COULD NOT MODIFY THE ARRHYTHMIC SUBSTRATE IN PATIENTS WITH PREVIOUS VENTRICULAR TACHYCARDIA/FIBRILLATION

Patients with low cardiac function are at high risk for ventricular arrhythmia (VA). Previous studies showed that cardiac resynchronization therapy (CRT) improved left ventricular remodeling and CRT responder had lower risk of VA than non-responder. However, little is known about the risk of VA among the CRT responder with or without history of VA. The purpose of this study is to investigate the association between VA risk and CRT response among the patients with or without history of VA. Among our cohort of 497 consecutive CRT patients, we retrospectively investigated 351 patients, which included primary and secondary prevention of VA. Exclusion criteria was hemodialysis, date deficit of left ventricular ejection fraction or ventricular volume. VA was defined as lasted ≥ 30s or treated by anti-tachycardia pacing or shock. CRT responders defined as ≥ 15% decrease of in left ventricular end-systolic volume and increase left ventricular ejection fraction ≥ 10% after CRT implantation. Two hundred and forty patients were CRT responder (68.4%), and 70 patients were indication for secondary prevention (19.9%). During a follow-up of 901 days (inter quartile range: 365-1737) 93 patients had VA events (CRT responder: 55pts, CRT non-responder: 38pts). Kaplan-Meier analysis showed the responder had lower risk of VA than the non-responder among all patients (log rank p=0.003) and patients for primary prevention (log rank p=0.004), though there was no significant difference among the patient for secondary prevention (log rank p=0.695). In addition, multivariate analysis showed that responder was independent predictor of VA among the patient for primary prevention (hazard ratio 0.50; 95% confidence interval 0.29-0.84, p=0.009), though responder was not predictor of VA among the patient for secondary prevention (p=0.83) The patients for secondary prevention remain at high risk of VA even among CRT responders. CRT response could not reduce VA substrate.

PO-05-192 LOCAL HETEROGENEITY OF LATE GADOLINIUM ENHANCEMENT PREDICTS VENTRICULAR ARRHYTHMIA IN HYPERTROPHIC CARDIOMYOPATHY

Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death in young people. Despite recent advances in risk stratification using cardiac magnetic resonance (CMR) imaging, risk prediction remains suboptimal. Improved risk stratification is therefore warranted. Whether local heterogeneity of Late Gadolinium Enhancement (LGE) signal is associated with ventricular arrhythmia remains unknown. To determine whether local heterogeneity of LGE signal on CMR predicts ventricular arrhythmia and appropriate shocks after implantable cardioverter defibrillator (ICD) implantation in patients with HCM. Local heterogeneity was quantified by LGE-CMR signal dispersion score and compared with cardiovascular outcomes in 179 HCM patients who underwent ICD implantation. The primary outcome was appropriate ICD shocks. During a median follow-up time of 7.3 years the event rate was 0.015 per person year. History of ventricular arrhythmia (HR 9.413, p<0.001) and sudden cardiac death (HR 13.82, p<0.001) were associated with receiving an appropriate ICD shock in both univariable and multivariable analyses. History of syncope, family history of sudden cardiac death, non-sustained ventricular tachycardia, left ventricular wall thickness and presence of LGE were not associated with the primary outcome. When compared to patients without ICD shock, patients who received ICD shocks had higher burden of LGE gray zone (16.8±7.5% vs 25.8±3.5% p<0.001) and scar (10.5±6.7% vs 18.7±4.3% p<0.001) on CMR. Importantly, patients with ICD shocks had a higher dispersion score (1.20 vs 0.97, respectively), signifying higher degree of LGE signal heterogeneity (p=0.047). Dispersion score, a marker of local LGE signal heterogeneity of scar and gray zone was associated with a higher burden of ICD shocks in HCM patients who received ICDs. Mechanistically, local LGE signal heterogeneity could represent complex scar. These results may contribute to improved risk stratification for ventricular arrhythmia in HCM patients.

Atrial Fibrillation and the Risk of Ventricular Arrhythmias and Cardiac Arrest: A Nationwide Population-Based Study.

Atrial fibrillation (AF) has been linked to an increased risk of ventricular arrhythmias (VAs) and sudden death. We investigated this association in hospitalised patients in France. All hospitalised patients from 2013 were identified from the French National database and included if they had at least 5 years of follow-up data. Overall, 3,381,472 patients were identified. After excluding 35,834 with a history of VAs and cardiac arrest, 3,345,638 patients were categorised into two groups: no AF (n = 3,033,412; mean age 57.2 ± 21.4; 54.3% female) and AF (n = 312,226; 78.1 ± 10.6; 44.0% female). Over a median follow-up period of 5.4 years (interquartile range (IQR) 5.0-5.8 years), the incidence (2.23%/year vs. 0.56%/year) and risk (hazard ratio (HR) 3.657 (95% confidence interval (CI) 3.604-3.711)) of VAs and cardiac arrest were significantly higher in AF patients compared to non-AF patients. This was still significant after adjusting for confounders, with a HR of 1.167 (95% CI 1.111-1.226) and in the 1:1 propensity score-matched analysis (n = 289,332 per group), with a HR of 1.339 (95% CI 1.313-1.366). In the mediation analysis, the odds of cardiac arrest were significantly mediated by AF-associated VAs, with an OR of 1.041 (95% CI 1.040-1.042). In hospitalised French patients, AF was associated with an increased risk of VAs and sudden death.

294 BEYOND BRUGADA SYNDROME: A COMMON ECG PATTERN IN AN UNCOMMON CLINICAL SCENARIO

Abstract Propofol infusion syndrome (PRIS) is a rare but potentially lethal side effect of propofol. In most cases it shows various combinations of signs such as unexplained metabolic acidosis, rhabdomyolysis, hepatomegaly, renal failure, hypertriglyceridemia, malignant arrhythmia and rapidly progressive cardiac failure. The development of coved ST elevation in the right precordial leads of the electrocardiogram (ECG), similar to that seen in the type I Brugada syndrome may be the first sign of cardiac instability. There is no specific treatment for PRIS. Successful management consists of an early recognition of its signs followed by a prompt propofol infusion termination. We present the case of a 35-year-old male affected by mild hypertension. He was found by his wife during a transitory loss of consciousness episode. He had resulted positive to Sars Cov 2 infection a day before and was symptomatic for fever and myalgia. An ambulance was immediately called and the patient was transferred to the emergency department for a suspected out-of-hospital-cardiac arrest. The initial one-lead ECG performed by the emergency physician was unremarkable. On arrival he was in a coma state but with stable hemodynamics. ECG showed only an asymmetric T wave inversion in V4-V6 leads. The cardiac echocardiogram did not show any major alterations. In the meantime, due to worsening of respiratory function, orotracheal intubation was performed and the patient was sedated with propofol, midazolam and fentanyl. Subsequently, an episode of atrial fibrillation was documented. Amiodarone infusion was started and the patient reverted to sinus rhythm after a few hours. The following day two episodes of Torsade de Pointes during prolonged QTc (660 ms) occurred. These arrhythmias were treated successfully with magnesium sulfate infusion. Blood analysis showed severe hypokalemia that was immediately corrected. After the hemodynamic stabilization the ECG showed a pattern highly resembling the Brugada pattern type 1 in the right precordial leads. Moreover CPK, myoglobin, high sensitivity troponin I levels started to rise, along with creatinine, triglycerides and markers of hepatic injury. Propofol had been administered continuously for eight days, so PRIS was suspected as the primum movens of this clinical scenario. Propofol infusion was immediately interrupted. Thereafter, the patient gradually improved and was extubated. As soon as the patient's hemodynamic conditions allowed it, a coronary CT and a cardiac MRI were performed, but were unremarkable. To further evaluate the case, a flecainide challenge test was performed, but no significant ECG change was induced. Nonetheless, given both the history of ventricular arrhythmia, the young age of the patient and the unexplained transitory loss of consciousness a subcutaneous defibrillator was implanted as a form of secondary prevention.

197: CONTINUATION OF AMIODARONE IN CRITICALLY ILL PATIENTS WITH ATRIAL FIBRILLATION

Introduction: Atrial fibrillation (AF) is the most common arrhythmia in critically ill patients in the intensive care (ICU), and leads to longer lengths of stay and an increased mortality. Beta-blockers (BB) are the first-line but are avoided in ICU due to negative inotropic effects in hemodynamically unstable patients. Amiodarone is commonly used to manage AF in ICU due to rate control properties with a minimal decrease in inotropy. Many patients inappropriately continued on amiodarone therapy after transitioning out of ICU, placing patients at increased risk of adverse effects. The purpose of this study was to evaluate the frequency of inappropriate amiodarone continuation after ICU transfer and on discharge. Methods: A retrospective cohort study evaluating patients with AF who were treated with amiodarone infusion between July 1, 2019, and July 1, 2021. Patients were included if they received amiodarone infusion and excluded with a history of ventricular arrhythmias, ICD or pacemaker, and pregnant or lactating mothers. The primary outcome was to assess the proportion of patients discharged on amiodarone. Secondary outcomes included percentage of patients converted to oral once hemodynamically stable, median ICU and hospital length of stay, and percentage of patients converted to BB. Results: A total of 117 patients were evaluated including 79 with chronic AF and 38 with new-onset AF. Amiodarone was continued on discharge in 2 (2.5%) patients in chronic AF group and no patients in new-onset AF group. No patients were converted to oral amiodarone on ICU discharge. Lastly, 28 (35.4%) patients with chronic AF were converted back to BB therapy prior to hospital discharge, while 6 (15.8%) patients were started on BB in new-onset AF group. Conclusions: Although amiodarone was appropriately switched from IV to oral and discontinued in the majority of the patient before ICU or hospital discharge, however, BB therapy was not started or resumed prior to discharge in the majority of patients.

Abstract 14926: VT LVAD Score and Survival Free From Ventricular Arrhythmias: The University of Michigan Experience

Introduction: Ventricular arrhythmias (VA) are a common complication after left ventricular assist device (LVAD) implantation and contribute to increased mortality. The VT LVAD Score was created to help stratify patients into four risk categories: Low Risk, Moderate Risk, High Risk, and Very High Risk. Hypothesis: We sought to assess the performance of the VT LVAD score at our institution. Methods: Consecutive patients who underwent LVAD placement from 2015-2019 were reviewed. VT LVAD scores were correlated with VA free survival (VA-FS). Only 1 patient was in the low-risk group and was excluded from analysis. Results: A total of 237 patients who underwent LVAD implant (age 57.9 ± 14.6 years, 180 male, 89 ischemic cardiomyopathy, 102 with prior VAs, 102 Heartmate 3) were included. Of the 5 variables included in the VT LVAD score, only prior VA was associated VA-FS (HR 3.09[1.89-5.03], p&lt;0.001 (Figure 1A), log rank p=0.003, Figure 1D). There was a significant difference in VA-FS between moderate versus both high and very high-risk groups (p=0.033 and p=0.029 respectively) as well as moderate vs high/very high-risk combined (p=0.041, Figure 1B). The significant difference in VA-FS between moderate vs high/very high-risk score groups persisted among all patients with prior VA (p=0.04, Fig 1C). No other between-group differences in VA-FS were seen (Figure 1B and 1C, p&gt;0.05 for all). Conclusions: Patients with a VT LVAD score of high or very high-risk had worse survival free from VA than patients with moderate-risk score, no other between group differences were noted. History of VA is a simple and powerful risk factor for late VA post LVAD.

Prognostic role of low QRS voltages in patients with cardiac amyloidosis

Abstract Introduction Cardiac amyloidosis (CA) is an underdiagnosed and heterogeneous cardiac disease characterized by the extracellular deposition of misfolded proteins in the cardiac tissue. Clinical manifestations are heterogeneous leading to progressive heart failure, often complicated by arrhythmias and conduction system disease. Among several sign and symptoms that are suspicious for the disease, named “red flags”, disproportionally low QRS voltages on the ECG has been described. Purpose The aim of this prospective observational study is to evaluate potential prognostic features of QRS amplitude in AL e ATTR CA patients. Methods All consecutive patients admitted to the Cardiomyopathy Clinic of our institution have been enrolled after receiving CA diagnosis, according to the current guidelines. We included all patients ≥18 years with a diagnosis of CA and written informed consent. A complete assessment including a standard 12-lead electrocardiogram (ECG) and echocardiogram was performed at enrollment. Low QRS voltages (LQRSV) was defined as a QRS total amplitude of ≤5 mm in every limb leads and ≤10 mm in every precordial lead. LQRSV was tested as an independent predictor of death from all causes (primary endpoint), hospitalization from cardiovascular causes, ventricular and supraventricular arrhythmias. Results Sixty patients (46 males, 77±12 years old) were enrolled, of which 18 (30%) met the criteria for LQRSV. Patients with LQRSV presented more frequently with an history of ventricular arrhythmia (27.8% vs. 6.7%, p=0.04), a lower left ventricular diastolic volume (31±7 vs. 44±18 ml/m2; p=0.04), and higher retinol-binding-protein 4 (9.3±2.2 vs 3.2±1.5 mg/dl; p=0.02). No differences were seen in the primary outcome (46% vs. 50%; p=NS; Figure 1) or in the secondary ones (cardiovascular hospitalization 25% vs. 21%; ventricular arrhythmias 12% vs 4%; supraventricular arrhythmias 29% vs 19%; all p=NS) between the two groups during a median follow up of 1.1 year. Conclusions In the present cohort of CA patients LQRSV did not emerge as independent predictor of all-cause mortality at 1 year. Although LQRSV is a recognized diagnostic “red-flag” in the work-up of CA, its role as prognostic marker remains unclear. Further studies with a longer follow-up are needed to better define the prognostic role of LQRSV among CA patients. Funding Acknowledgement Type of funding sources: None.

Right ventricular longitudinal strain on CMR predicts ventricular arrhythmias and mortality in cardiac sarcoidosis

BackgroundRight ventricular (RV) dysfunction and late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) are associated with ventricular arrhythmias (VA) and mortality in cardiac sarcoidosis (CS). However, image resolution limits the detection of RV LGE. Global longitudinal RV strain (RVS) correlates to RV scar on electroanatomical mapping and RV function. ObjectiveWe evaluated the association between RVS on CMR and VA/death (combined-primary-endpoint (CPE)) in patients with CS. MethodsRVS and RV LGE on MRI were retrospectively compared to variables known to predict outcomes in 66 patients with CS. Outcomes were obtained from electronic medical records and implantable cardioverter defibrillator (ICD) interrogations over median [IQR] 3.7[1.7, 6.3] years. Cox proportional hazard models were used to evaluate survival. Harrell's C-statistic was used to compare variables in risk prediction models. Results62.1 % of patients were male, with a mean age [SD] of 52.3 [9.6] years and left ventricular ejection fraction (LVEF) of 51.1[17.5]%. 9 patients with the primary endpoint were more likely to be Caucasian (p = 0.01) with prior VAs (p = 0.002), be on anti-arrhythmic drugs (p = 0.001) with an ICD (p = 0.002). In multivariable analyses adjusted for age, race, and history of VA, RVS (1.18 [1.05–1.31], p = 0.004), RV EDVI (1.08[1.01, 1.14], p = 0.02), and LV LGE (1.07[1.00, 1.13], p = 0.04) predicted the CPE. Risk prediction models including RVS (Cstatistic 0.94), outperformed those including RV and LV LGE (0.89–0.92). ConclusionRVS on CMR was the best predictor of VA and mortality in CS.

Feasibility of an automatic ultrasonographic image acquisition system associated with an artificial intelligence algorithm for real-time monitoring of cardiac motion during cardiac radio-ablation

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This publication is part of a project that has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 954783. Background Stereotactic arrhythmia radio-ablation (STAR) is a promising strategy for the non-invasive treatment of ventricular arrhythmias (VA). The management of the cardio-respiratory motion of the target and the reduction of the uncertainties related to patients’ positioning are two of the main challenges that STAR has to overcome. A prototype of a system was developed that can automatically acquire and interpret echocardiographic images using an artificial intelligence (AI) algorithm to calculate cardiac displacement in real-time. Purpose To evaluate the feasibility of this automatic acquisition system in patients with a history of VA. Methods We conducted a single center, feasibility study enrolling consecutive patients with a history of VA. Echocardiographic images were automatically acquired from the parasternal and apical views with a dedicated probe. The system was designed to hold the probe fixed to the chest in the supine position during both free-breathing and short expiratory breath-hold sequences, to simulate STAR treatment. The primary endpoint was the percentage of patients reaching a score ≥2 in a multi-parametric assessment evaluating the quality of automatically acquired images in terms of: A - allowing a proper identification of the cardiac cycle phase using the AI algorithm, B - allowing a correct measurement of the heart displacement by the AI algorithm, C - ability to visually distinguish typical cardiac structures, and D - stability of the image throughout the respiration cycle. Moreover, we investigated the potential impact of clinical and demographic characteristics on achieving the primary outcome. Results From May to September 2021, we enrolled 24 patients (63±14 years, 21% females). All of them had a history of VA and 21 (88%) had an ICD. Eight patients (33%) had coronary artery disease, 12 (50%) had non-ischemic cardiomyopathy, and 3 had idiopathic VA. Parasternal as well as apical images were obtained from all patients except from one, in whom parasternal view could not be collected due to the patient’s inability to maintain the supine position. The primary outcome was achieved in 23 patients (96%) for the apical view, in 20 patients (87%) for the parasternal view, and in all patients in at least one of the two views. The images quality was maximal (i.e. score=4) in at least one of the two windows in 19 patients (79%). Atrial fibrillation arrhythmia was the only clinical characteristics associated with a poor score outcome in both imaging windows (apical p=0,022, parasternal p=0,014). Conclusion An automatic ultrasonographic image acquisition system associated with an AI algorithm is feasible for real-time monitoring of cardiac motion in patients with a history of VA. The possibility of real-time, non-invasive monitoring of cardiac position would lead to a significant improvement in the quality and safety of STAR treatment, particularly in case of treatment with heavy particles such as protons and carbon ions.

Threshold values by electrocardiogram and echocardiography indicating transition to an arrhythmic phenotype in cardiac laminopathies: a primary prevention cohort study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): 1) Precision Health Care Center for optimized cardiac care (ProCardio) supported by the Norwegian Research Council 2) European Research Area Network on Cardiovascular Diseases (ERA-CVD) Background/Introduction Cardiac laminopathies are malignant and pro-arrhythmic variants of familial dilated cardiomyopathy caused by mutations in the LMNA gene. Correct timing of implantable cardioverter defibrillator (ICD) implantation is crucial in these patients, but optimal timing of primary preventive ICD remains a great challenge in clinical practice. Purpose We aimed to explore threshold values by electrocardiogram and echocardiography to identify transition to a more arrhythmic phenotype in LMNA disease. Methods We prospectively included consecutively recruited LMNA genotype positive patients in a primary prevention cohort study. Patients underwent repeated clinical-, electrocardiogram- and echocardiographic examinations during long-term follow-up. Ventricular arrhythmia was defined as sustained ventricular tachycardia, appropriate therapy by a primary preventive ICD or aborted cardiac arrest. We explored electrocardiographic and echocardiographic cut-off values for increased odds of experiencing first-time ventricular arrhythmia during follow-up by threshold regression analyses. The cardiac phenotype at time of ventricular arrhythmia was assessed from electrocardiogram recording and echocardiographic examinations acquired ±12 months of the arrhythmic event. Results We included 94 LMNA genotype positive patients with no history of ventricular arrhythmia at baseline (age 38±15 years, 32% probands, 53% female). Incidence of VA was 20% (19 patients) during 4.6 (inter quartile range [IQR] 2.1-7.3) years follow-up, at mean age 50±11 years. We analysed 261 electrocardiogram recordings and 536 echocardiographic examinations. At time of first ventricular arrhythmia, most patients had pronounced conduction delay (PR interval 312 [IQR 204-430] ms) and evident left ventricular pathology (left ventricular ejection fraction [LVEF] 40±12 %, left ventricular end diastolic volume indexed [LVEDVi] 83±22 ml/m2). Electrocardiographic threshold values for increased arrhythmic risk were PR interval 280 ms (OR 1.9, 95% CI 1.5-2.5, per 5 ms increase after threshold, p&amp;lt;0.001), and QRS width 108 ms (OR 2.6, 95% CI 1.9-3.7, per 5 ms increase after threshold, p&amp;lt;0.001). Echocardiographic threshold values were LVEF 44 % (OR 1.6, 95% CI 1.4-2.0, per 5 % decrease after threshold, p&amp;lt;0.001), and LVEDVi threshold 77 ml/m2 (OR 1.5, 95% CI 1.3-1.8, per 5 ml/m2 increase after threshold, p&amp;lt;0.001) (Figure). Conclusions Incidence of first time ventricular arrhythmic event was 20% in LMNA genotype positive patients during 4.6 years of follow up. PR interval &amp;gt;280ms, LVEF &amp;lt;44% or LVEDVi &amp;gt;77 ml/m2 should alert the clinician of transition to a more arrhythmic phenotype in cardiac laminopathies and implantation of a primary preventive ICD should be considered.

Studying the relation between post-infarction ventricular arrhythmia and left ventricular myocardium thinning on computed tomography images using explainable deep learning

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): National Research Agency, 3IA Côte d’Azur (ANR-19-P3IA-0002), IHU Liryc (ANR- 10-IAHU-04) Background Infarct heterogeneity plays a critical role in the development of scar-related ventricular arrhythmias (VA). Wall thickness (WT) from CT was shown to correlate with arrhythmogenic sites in the context of ablation. Purpose To analyze the relationship between WT distribution and the presence VAs in patients with history of myocardial infarction (MI). Methods From 2010 to 2020, we retrospectively included consecutive patients who underwent CT more than 1 year after MI.Automated LV wall segmentation, reorientation, WT computation and flattening methods were applied to obtain 2D WT bullseye maps.The population was divided into a training set (3/4) and a testing set (1/4). On the training set, a conditional variational autoencoder (CVAE) model was trained to encode the WT map in its latent representation,which was then used by a classifier model to predict VA. For each prediction, a gradient back-projection method was used to generate attention maps highlighting the bullseye region most influential in the model’s decision. The ability of the trained CVAE to identify patients with VA was then assessed on the test population, and compared to that of other clinical variables (age, gender, LVEF, scar size). Results 641 patients were included (age 73±7 years, 83% males, LVEF 46±10%), including 166 (26%) with history of VA. From original CT images, automated processing methods allowed for the obtention of a WT bullseye, a VA prediction and an attention map in less than 2 min. On the testing population, univariable correlates of VA were LVEF (P&amp;lt;0.001), scar size defined as WT area (P&amp;lt;0.001), CVAE prediction (P&amp;lt;0.001), and male gender (P=0.007). Multivariable analysis identified CVAE prediction and male gender as independent VA correlates (P&amp;lt;0.001 and P=0.01, R2=0.364), while LVEF and scar size were not (P=0.052 and P=0.60). The CVAE model identified patients with VA with a sensitivity/specificity of 0.87/0.74. The analysis of attention maps confirmed that the CVAE actually used the MI region to predict VA, and showed that the CVAE was filtering out areas of physiological WT, thereby outperforming simple WT thresholding. Conclusions Fully automated analysis of WT from CT images is feasible in patients with MI, and allows for the extraction of robust markers of VA, outperforming conventional risk stratifiers

Incidence and predictors of cardiac arrhythmias in patients with systemic sclerosis

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Heart involvement in systemic sclerosis patients is frequent and represents a negative prognostic factor with around 25% of SSc patients dying from cardiovascular related causes. Cardiac arrhythmias represent 6% of the overall causes of death in SSc patients. Not only a plethora of conditions typical of the disease seem to favour the presence of an arrhythmic substrate such as microvascular disease or fibrosis but autoimmunity itself has been recognized as a pathogenic mechanism for cardiac arrhythmias. Purpose The aim of our study was to investigate the incidence of arrhythmias in patients with systemic sclerosis and identify potential predictors. Methods Prospective longitudinal study enrolling all consecutive patients with a diagnosis of SSc and no overt cardiac disease nor pulmonary hypertension. Echocardiographic parameters and GLS were obtained at baseline and at each follow up as well as 12 lead ECG. Presence of atrial fibrillation (AF), atrial tachycardia (AT), ventricular ectopic beats &amp;gt;1000/24 h (VEB), supraventricular ectopic beats (SVEB), bundle branch block (BBB) and atrioventricular block (AVB) was registered. Results 160 patients (144 females, 90%, mean age 59±14 years) were enrolled from June 2016 to December 2021. At enrolment, 11.3% of patients with SSc presented a previous history of supraventricular arrhythmia (5.6% supraventricular ectopic beats, 3.1% atrial fibrillation, 2.5% atrial flutter) and 5.6% a history of ventricular arrhythmia (5.0% ventricular ectopic beats, 0.6% ventricular tachycardia). After a median follow-up of 3.1 years (95% CI 1.4-4.8 years), five patients (3.1%) died of cardiovascular causes, of which three (1.8%) experienced a sudden cardiac death. During the same period, 16 patients (10%) presented a new diagnosis of supraventricular arrythmia (8.7% atrial fibrillation, 1.3% atrial flutter) and two patients (1.2%) a new diagnosis of ventricular tachycardia. PR interval significantly increased during the 3.1-year follow-up (154±27 vs. 178±32 ms; p=0.013), as well as corrected QT interval (420±23 vs. 436±19 ms; p=0.001). New diagnosis of complete right and left bundle branch block was made in 18 (11.2%) and two (1.2%) of all SSc patients. Diagnosis of pulmonary arterial hypertension was associated with a 4-fold and a 10-fold increased risk of supraventricular and ventricular arrhythmias, respectively (Figure 1). A diffuse SSc variant (p=0.049), indexed right (p=0.020) and left atrial volumes (p=0.035), and E/E’ ratios (p=0.016) were all associated with an increased risk of supraventricular arrhythmias. TAPSE (p=0.040), as well as right (p=0.030) global longitudinal strain were associated with an increased risk of ventricular arrhythmias. Conclusions Ssc patients are often by an arrhythmic profile with an increased risk of supraventricular and ventricular events as well as sudden cardiac death. A comprehensive cardiological work up may help in lowering the risk of arrhythmic complications.

Feasibility of an Automatic Ultrasonographic Image Acquisition System Associated With an Artificial Intelligence Algorithm for Real-Time Monitoring of Cardiac Motion During Cardiac Radio-Ablation.

BackgroundThe management of the cardio-respiratory motion of the target and the reduction of the uncertainties related to patient's positioning are two of the main challenges that stereotactic arrhythmia radio-ablation (STAR) has to overcome. A prototype of a system was developed that can automatically acquire and interpret echocardiographic images using an artificial intelligence (AI) algorithm to calculate cardiac displacement in real-time.MethodsWe conducted a single center study enrolling consecutive patients with a history of ventricular arrhythmias (VA) in order to evaluate the feasibility of this automatic acquisition system. Echocardiographic images were automatically acquired from the parasternal and apical views with a dedicated probe. The system was designed to hold the probe fixed to the chest in the supine position during both free-breathing and short expiratory breath-hold sequences, to simulate STAR treatment. The primary endpoint was the percentage of patients reaching a score ≥2 in a multi-parametric assessment evaluating the quality of automatically acquired images. Moreover, we investigated the potential impact of clinical and demographic characteristics on achieving the primary endpoint.ResultsWe enrolled 24 patients (63 ± 14 years, 21% females). All of them had a history of VA and 21 (88%) had an ICD. Eight patients (33%) had coronary artery disease, 12 (50%) had non-ischemic cardiomyopathy, and 3 had idiopathic VA. Parasternal, as well as apical images were obtained from all patients except from one, in whom parasternal view could not be collected due to the patient's inability to maintain the supine position. The primary endpoint was achieved in 23 patients (96%) for the apical view, in 20 patients (87%) for the parasternal view, and in all patients in at least one of the two views. The images' quality was maximal (i.e., score = 4) in at least one of the two windows in 19 patients (79%). Atrial fibrillation arrhythmia was the only clinical characteristics associated with a poor score outcome in both imaging windows (apical p = 0.022, parasternal p = 0.014).ConclusionsThese results provide the proof-of-concept for the feasibility of an automatic ultrasonographic image acquisition system associated with an AI algorithm for real-time monitoring of cardiac motion in patients with a history of VA.