Occurrence Of Ventricular Arrhythmias Research Articles

LVNC or hyper-trabeculated LV, are we missing something?

Abstract Introduction LVNC is a heterogeneous poorly understood entity characterized by prominent myocardial trabeculation.(1) It often overlaps with other phenotypes such as DCM, HCM.(2) Incidence of SCD is highly variable, however it may account for about 50% of all mortality in LVNC.(3) Risk stratification of SCD is a complex matter. Despite that current guidelines recommend following the same principles of 1ry prevention as in DCM based on similar CV mortality risk, it seems of utmost importance to identify additional features which could be specifically associated with LVNC and contributing to a higher risk of adverse events particularly ventricular arrhythmia (VA). Purpose To identify possible high risk features for prediction of ventricular arrhythmia in the form of documented NSVT, VT, or VF in LVNC. Methods This is a retrospective single centre cohort study of patients fulfilling the LVNC defining criteria from 2018 to 2023. Patients’ data were reviewed for family history of cardiomyopathies or SCD, clinical presentation, ECGs data in the form of QRS duration, QTc interval and Tp-e, Holter analysis, CIEDs interrogation if present and MRI data including LVEF, volumes, fibrosis burden and distribution, NC/C ratio, NC / LV global mass ratio, global longitudinal strain"GLS", global circumferential strain "GCS" , global radial strain "GRS" , extent of hypertrabeculation, RV involvement in the form of EF, volumes, hypertrabeculation. Results A total of 42 patients were included (34+/- 17 years of age, 57% males). 5 patients of our cohort were pediatrics. Mean LVEF 45%. LGE was detected in 14% of cases, RV involvement in 38 %. Ventricular arrhythmia were present in 15 patients (35%), of which 6 patients had malignant ventricular arrhythmia. LVEF, NC/LV global mass ratio, LVGLS, LVGCS were found to be significantly correlated with the occurrence of VA with cut-off values of <43%, >31%, <-15 and <-13.5 respectively. While positive FH, RV involvement, pattern, burden of LV fibrosis and ECG parameters didn’t significantly increase the incidence of VA. In a multivariate regression analysis NC to LV global mass ratio was the sole independent predictor of VA ( p value=0.024). ICDs were implanted in 10 cases, 8 were for 1ry prevention based on clinical judgement, 4 of them received appropriate ICD therapy. Conclusion LVNC is associated with increased risk of VA. In addition to clinical assessment and LVEF, CMR can add a different insight for risk stratification. Interestingly, LGE wasn’t associated with significantly increased risk of VA "taking into consideration LGE was found only in 14% of cases" highlighting the potential role the trabeculated myocardium in the pathophysiology of VA by altering the electrical stability of the heart. Finally, these findings could contribute in answering an ongoing question; Should LVNC with its unique characteristics be treated as a special entity with its own high-risk criteria for VA and SCD?LV NC/global mass ration and GLSDemographic,clinical,ECG and MRI data

Stratification of arrhythmic risk in patients admitted for acute coronary syndrome: the role of the machine learning-derived PRAISE score

Abstract Funding Acknowledgements None. Background Patients with acute coronary syndrome (ACS) have a high arrhythmic burden, and either ventricular and supraventricular arrhythmias are very common during hospitalization[1]. Patients who develop arrhythmias show higher mortality and worse prognosis. The PRAISE (Prediction of Adverse Events Following an Acute Coronary Syndrome) score is a machine-learning based model for predicting 1-year all cause death, recurrent acute myocardial infarction and major bleedings in patients after ACS[2]. To date, its role to predict arrhythmic complications in ACS remains unknown. Purpose We hypothesized that patients with higher PRAISE score have a higher arrhythmic burden. Aim was to evaluate in a prospective protocol the PRAISE score capability for identifying patients with ACS at higher risk of arrhythmic complications during in-hospital stay. Methods A total of 365 consecutive patients admitted to our cardiac intensive care unit for ACS and undergoing percutaneous coronary intervention were enrolled. All patient was monitored by continuous electrocardiogram during hospitalization. The PRAISE score was obtained for each patient <24 hours from admission. Patients were divided into 2 groups based on the results of the PRAISE score for all-cause of death as patients without high PRAISE score (e.g. with low to intermediate risk, n=350) and patients with high PRAISE score (e.g. with high risk, n=15). The occurrence of atrial fibrillation (AF) and ventricular arrhythmias (VAs) up to discharge was recorded. AF was defined by detection of at least one episode of uncoordinated atrial electrical activation and irregular R-R intervals, in absence of distinct repeating P waves and with irregular atrial activations lasting at least 5 minutes. We considered as VAs all episodes of ventricular non-sustained tachycardia, sustained ventricular tachycardia and ventricular fibrillation. Results ROC curve analysis indicated a significant relationship between high PRAISE score and risk of both in-hospital AF (AUC 0.89, 95%CI 0.82-0.94, p=0.0001) and VAs (AUC 0.69, 95%CI 0.64-0.75, p=0.0001). A high PRAISE score had a specificity of 99% for AF and 92% for VAs. By Kaplan-Meier analysis, patients with high PRAISE score more frequently developed AF (30% vs 4% in those without high score; log rank p=0.00001) and VAs (77% vs 35%; log rank p=0.00001). Multivariate analysis showed that a high PRAISE score was an independent predictor of both AF (HR 4.08, 95%CI 1.14-14.58, p=0.030) and VAs (HR 2.36, 95%CI 1.08-5.14, p=0.030). Conclusions In patients hospitalized for ACS, the PRAISE score has a comprehensive capability to identify with high specificity those patients prone to develop arrhythmic events during hospitalization. This may be important in order to stratify patients with higher arrhythmic risk in whom individualized strategies may improve the clinical outcome.Baseline features of the populationKaplan-Meier anaysis

Extension of interval between adjacent pulse delivery cycles to deal with myocardial ischemia by intravascular lithotripsy: case report

BackgroundIntravascular lithotripsy (IVL) represents a novel approach in the management of coronary calcification. This technique employs acoustic pressure waves, generated by a shockwave balloon, to effectively fracture both superficial and deep calcification in situ. The efficacy and safety of IVL have been convincingly demonstrated through the Disrupt CAD I-IV studies. While IVL is associated with the occurrence of atrial and ventricular arrhythmias, there is no evidence to indicate it causes myocardial ischemia.Case DescriptionA 71-year-old man was admitted presenting with chest pain. His previous coronary angiography revealed stenosis and calcification in the left anterior descending branch. An attempt to predilate the lesion using two Lacrosse non-slip element balloons was unsuccessful. Ventricular premature beats and transient ST-segment depression were captured during the utilization of IVL. The operator gradually extended the pulse emission interval across two consecutive cycles to mitigate myocardial ischemia. Notably, when the interval reached 30s, the patient had no chest pain or ST-segment changes. Subsequent images of intravascular ultrasound confirmed calcification ruptures. Therapeutic intervention included the placement of a stent and the application of a drug-coated balloon in the left anterior descending branch. A telephonic follow-up six months later indicated the patient had no discomfort.ConclusionsThis case underscores the effectiveness of gradually extending the pulse emission interval as a strategic complement to the clinical application of IVL. In certain clinical scenarios, it may become imperative to suspend the pulse delivery to improve myocardial blood supply.

Machine Learning for Prediction of Ventricular Arrhythmia Episodes from Intracardiac Electrograms of Automatic Implantable Cardioverter-Defibrillators

BackgroundDespite the implantable cardioverter defibrillator’s (ICD) effectiveness in saving patients with life-threatening ventricular arrhythmias (VAs), the temporal occurrence of VA following ICD implantation is unpredictable. ObjectiveApply machine learning (ML) to intracardiac electrograms (IEGMs) recorded by ICDs as a unique biomarker for predicting impending VAs. MethodsThe study included 13,516 patients who received BIOTRONIK ICDs and enrolled in the CERTITUDE registry between 01/01/2010 to 12/31/2020. Database extraction included IEGMs from standard quarterly transmissions and VA event episodes. The processed IEGM data were pulled from device transmissions stored in a centralized Home Monitoring Service Center and reformatted into an analyzable format. Long- (baseline or first scheduled remote recording), mid-(scheduled remote recording every 90 days), or short-range predictions (IEGM within 5 seconds before the VA onset) were used to determine whether ML-processed IEGMs predicted impending VA events. Convolutional neural network classifiers using ResNet architecture were employed. ResultsOf 13,516 patients (male 72%, age 67.5 ± 11.9 years), 301,647 IEGM recordings were collected; 27,845 episodes of sustained VT/VF were observed in 4,467 patients (33.0%). Neural networks based on CNN using ResNet-like architectures on far-field IEGMs yielded an AUC of 0.83 with a 95% confidence interval of [0.79, 0.87] in the short-term, while the long- and mid-range analyses had minimal predictive value for VA events. ConclusionIn this study, applying ML to ICD-acquired IEGMs predicted impending VT/VF events seconds before they occurred, whereas mid- to long-term predictions were not successful. This could have important implications for future device therapies.

Atorvastatin, etanercept and the nephrogenic cardiac sympathetic remodeling in chronic renal failure rats.

Chronic renal failure (CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia (VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this process. A total of 48 rats were randomly divided into sham operation group (Sham group), CRF group, CRF + atorvastatin group (CRF + statin group), and CRF + etanercept group (CRF + rhTNFR-Fc group). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43 (GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent assay. Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay, immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + rhTNFR-Fc group. In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept could downregulate the expression of TNF-α or inhibit its activity, thus inhibited the above effects, and reduced the occurrence of VA and sudden cardiac death.

Leukocyte Ig-like receptor B4 (Lilrb4a) alleviates cardiac dysfunction and isoproterenol-induced arrhythmogenic remodeling associated with cardiac fibrosis and inflammation

BackgroundHeart failure is usually accompanied by activation of the sympathetic nerve, and excessive activation of the sympathetic nerve promotes cardiac remodeling and cardiac dysfunction. In the isoproterenol (ISO)–induced animal model, it is often accompanied by myocardial hypertrophy, fibrosis, and inflammation. Leukocyte immunoglobulin-like receptor B4a (Lilrb4a), an immunosuppressive regulatory receptor, plays a vital role in cardiovascular disease. However, the effect of Lilrb4a on ventricular arrhythmia in an ISO-induced mouse model remains unclear. ObjectiveThe purpose of this study was to explore the role and molecular mechanism of Lilrb4a in ISO-induced arrhythmogenic remodeling. MethodsLilrb4a knockout mice and Lilrb4a overexpression mice were infused with ISO (15 mg/kg per 24 hours, 4 weeks). Echocardiography and histology evaluations of myocardial hypertrophy and cardiac structural remodeling were conducted. Surface electrocardiography and electrophysiologic examination were used to evaluate cardiac electrical remodeling and susceptibility to ventricular arrhythmias. Quantitative reverse transcriptase–polymerase chain reaction analysis and Western blotting were used to detect the expression levels of ion channel proteins and signal pathway proteins. ResultsThe results discovered that ISO induced cardiac hypertrophy, fibrosis, and inflammation and led to electrical remodeling and the occurrence of ventricular arrhythmias. Lilrb4a alleviated cardiac structural and electrical remodeling and protected against the occurrence of ventricular arrhythmias in ISO-induced mice by gain-of-function or loss-of-function approaches. The mechanism is that Lilrb4a inhibited nuclear factor κB signaling and p38 signaling activation mediated by transforming growth factor kinase 1. ConclusionLilrb4a alleviates cardiac dysfunction and ISO-induced arrhythmogenic remodeling associated with cardiac fibrosis and inflammation through the regulation of nuclear factor κB signaling and p38 signaling activation.

What Do We Know So Far About Ventricular Arrhythmias and Sudden Cardiac Death Prediction in the Mitral Valve Prolapse Population? Could Biomarkers Help Us Predict Their Occurrence?

To summarize currently available data on the topic of mitral valve prolapse (MVP) and its correlation to the occurrence of atrial and ventricular arrhythmias. To assess the prognostic value of several diagnostic methods such as transthoracic echocardiography, transesophageal echocardiography, cardiac magnetic resonance, cardiac computed tomography, electrocardiography, and electrophysiology concerning arrhythmic episodes. To explore intra and extracellular biochemistry of the cardiovascular system and its biomarkers as diagnostic tools to predict rhythm disturbances in the MVP population. MVP is a common and mainly benign valvular disorder. It affects 2-3% of the general population. MVP is a heterogeneous and highly variable phenomenon with three structural phenotypes: myxomatous degeneration, fibroelastic deficiency, and forme fruste. Exercise intolerance, supraventricular tachycardia, and chest discomfort are the symptoms that are often paired with psychosomatic components. Though MVP is thought to be benign, the association between isolated MVP without mitral regurgitation (MR) or left ventricle dysfunction, with ventricular arrhythmia (VA) and sudden cardiac death (SCD) has been observed. The incidence of SCD in the MVP population is around 0.6% per year, which is 6 times higher than the occurrence of SCD in the general population. Often asymptomatic MVP population poses a challenge to screen for VA and prevent SCD. Therefore, it is crucial to carefully assess the risk of VA and SCD in patients with MVP with the use of various tools such as diagnostic imaging and biochemical and genetic screening.

Is it safe to give birth with an activated implantable cardioverter-defibrillator: A multicentre observational study.

Data and guidelines are lacking, so implantable cardioverter-defibrillators (ICDs) are often deactivated during labour to prevent inappropriate shocks. This study aimed to ascertain the safety of an activated ICD during labour. An observational study was performed. Dutch hospitals. A total of 41 childbirths were included of 26 patients who gave birth between February 2009 and November 2018 after receiving an ICD in our tertiary hospital. Five of these childbirths were attended by the research team between December 2018 and August 2020, during which the ICD remained active. Groups were made based on ICD status during labour. Patients who gave birth with an activated ICD at least once were stratified to the activated ICD group. Patients' files were checked and patients received a questionnaire about childbirth perceptions and treatment preferences. The differences in ordinal data resulting from the questionnaire were calculated using a chi-square or Fisher's exact test. Primary outcome was inappropriate ICD therapy and occurrence of ventricular arrhythmias requiring treatment. During the 41 childbirths, no inappropriate shocks or ventricular arrhythmias occurred during labour. All patients in the activated ICD group (n = 13) preferred this setting, while 8 of the 13 patients in the deactivated ICD group preferred activation (p = 0.002). Reasons included avoiding hemodynamic monitoring, magnet placement, or labour induction to facilitate technician availability. This study shows no evidence that labour and birth in women with an activated ICD are unsafe, as there were no ventricular arrhythmias or inappropriate therapy. In addition, most patients prefer an activated ICD during labour.

Determinants of Ventricular Arrhythmias in Mitral Valve Prolapse

BackgroundMitral valve prolapse (MVP) may be associated with ventricular arrhythmias (VA) even in the absence of significant valvular regurgitation. Curling, mitral annulus disjunction (MAD) and myocardial fibrosis (late gadolinium enhancement [LGE]) may account for arrhythmogenesis. ObjectivesThis study investigated the determinants of VA in patients with MVP without significant regurgitation. MethodsThis study included 108 patients with MVP (66 female; median age: 48 years) without valve regurgitation. All patients underwent 12-lead electrocardiography, 12-lead 24-hour electrocardiographic Holter monitoring, exercise stress test, and cardiac magnetic resonance. Patients were divided into 2 groups (arrhythmic and no-arrhythmic MVP), according to the presence of VA with a right bundle branch block pattern. ResultsThe 62 patients (57%) with arrhythmic MVP showed: 1) higher MAD (median length: 6.0 vs 3.2 mm; P = 0.017); 2) higher prevalence of curling (79% vs 52%; P = 0.012); and 3) higher prevalence of left ventricular LGE (79% vs 52%; P = 0.012). Mediation analysis showed that curling had both a direct (P = 0.03) and indirect effect mediated by LGE (P = 0.04) on VA, whereas the association between MAD and VA was completely mediated by LGE. Patients with severe VA showed more pronounced morphofunctional alterations, in terms of MAD (7.0 vs 4.6 mm; P = 0.004) and presence and severity of curling (respectively, 91% vs 64%; P = 0.010; and 4 vs 3 mm; P = 0.004), compared to those without severe VA. ConclusionsIn patients with MVP the occurrence of VA with right bundle branch block morphology is the expression of more severe morphologic, mechanical, and tissue alterations. Curling has both a direct and an indirect effect on VA.

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.

Lack of temporal correlations between COVID pandemic waves and the occurrence of malignant ventricular arrhythmias

Lack of temporal correlations between COVID pandemic waves and the occurrence of malignant ventricular arrhythmias

Синдром недостаточности высвобождения кальция - редкий вариант катехоламинергической полиморфной желудочковой тахикардии

Authors present a difficult-to-diagnose clinical case of cotecholaminergic polymorphic ventricular tachycardia (CPVT), a rare hereditary disease, which is characterized by mutations most often in the RYR2 gene with increased function of the ryanodine receptor, which in its turn is the main protein of calcium channels in the sarcoplasmic reticulum of cardiomyocytes. The mechanism of development of the pathology is based on late post-depolarization, which is a trigger for the occurrence of severe ventricular arrhythmias associated with a high risk of sudden cardiac death. Ventricular arrhythmias in children with CPVT can causally be reproduced using an exercise test at a low heart rate threshold. However, there have been reports of sudden cardiac death in individuals who had the loss-of-function RyR2 mutations and who have nevertheless had negative stress test results. The main clinical manifestation is syncope, the genesis of which may remain unknown for a long time. The described clinical case demonstrates the complexity of diagnosis, for which the routine cardiological examination isn’t enough. Specialists therefore have difficulties in making the correct diagnosis and determining the patient management tactics.

AIEgen-Based Covalent Organic Frameworks for Preventing Malignant Ventricular Arrhythmias Via Local Hyperthermia Therapy.

The engineering of aggregation-induced emission luminogens (AIEgen) based covalent organic frameworks (COFs), TDTA-COF, BTDTA-COF, and BTDBETA-COF are reported, as hyperthermia agents for inhibiting the occurrence of malignant ventricular arrhythmias (VAs). These AIE COFs exhibit dual functionality, as they not only directly modulate the function and neural activity of stellate ganglion (SG) through local hyperthermia therapy (LHT) but also induce the browning of white fat and improve the neuroinflammation peri-SG microenvironment, which is favorable for inhibiting ischemia-induced VAs. In vivo studies have confirmed that BTDBETA-COF-mediated LHT enhances thermogenesis and browning-related gene expression, thereby serving a synergistic role in combating VAs. Transcriptome analysis of peri-SG adipose tissue reveals a substantial downregulation of inflammatory cytokines, highlighting the potency of BTDBETA-COF-mediated LHT in ameliorating the neuroinflammation peri-SG microenvironment and offering myocardial and arrhythmia protection. The work on AIE COF-based hyperthermia agent for VAs inhibition provides a new avenue for mitigating cardiac sympathetic nerve hyperactivity.

Hospital Outcomes of Spontaneous Coronary Artery Dissection With Concurrent Ventricular Arrhythmias

BackgroundWhile patients with spontaneous coronary artery dissection (SCAD) occasionally present with concurrent ventricular arrhythmias (VA), the impact of VA on in-hospital outcomes in the United States (US) is not well-established. This study aims to analyze in-hospital outcomes of patients with SCAD and concurrent VA and to determine the factors associated with VA occurrence in this high-risk population in the US. MethodsUsing the Nationwide Readmissions Database, our study included patients age 18 years or older who had SCAD between 2017 and 2020. We categorized the cohort into 2 groups depending on the presence of VA during hospitalization. In-hospital outcomes were assessed between SCAD patients with VA and those without. Weighted analysis was performed. We analyzed the independent factors associated with VA occurring among SCAD patients through univariable and multivariable analyses. ResultsEight hundred seventy-seven SCAD patients were included in the study: 118 (13.5%) with VA and 759 (86.6%) without. SCAD patients with concurrent VA were associated with higher rates of early mortality (10.2% vs 2.0%; P < .01), prolonged index hospital stay (≥7 days) (33.1% vs 11.7%; P < .01), and non-home discharge (21.2% vs 5.9%; P < .01). The length of hospital stay was longer in the SCAD with concurrent VA group (7.39 days vs 3.58 days; P < .01), and the median cumulative cost of hospitalization was also higher in this group ($31,451 vs $13,802; P < .01). SCAD patients with concurrent VA had increased in-hospital adverse events: acute heart failure, cardiac arrest, cardiogenic shock, cerebral infarction, pulmonary edema, and acute kidney injury. In multivariable analysis, the independent factors associated with VA occurrence among SCAD patients were chronic liver disease (aOR, 3.42; 95% CI, 1.43-8.20; P < .01) and heart failure (aOR, 5.63; 95% CI, 3.36-9.42; P < .01). ConclusionsConcurrence of VA among SCAD patients was associated with poorer in-hospital outcomes. Heart failure and chronic liver disease were the independent factors associated with VA occurrence in SCAD patients.

Functional mitral regurgitation and ventricular arrhythmias in patients with cardiac resynchronization therapy

Abstract Introduction In patients with heart failure (HF), the occurrence of ventricular arrhythmias (VAs) is associated with prognosis, and advanced HF can cause VAs. In HF patients developed moderate to severe functional mitral regurgitation (FMR), a transcatheter mitral valve repair therapy has significantly reduced the hospitalization and mortality rates compared to guideline-directed medical therapy. Although the mechanisms of arrhythmias are multiple, it is unclear whether FMR is involved in the development of VAs advanced HF patients. Methods and results We retrospectively examined 176 cardiac resynchronization therapy (CRT) patients (78% men, median age 67 years) without FMR before CRT implanted between 2010 and 2018. Worsening FMR was defined as developing moderate to severe FMR after CRT. During median follow-up of 40 (quartile range, 23-60) months, worsening FMR was detected in 26 (15%) patients at a median of 30 (quartile range, 12–75) months after CRT implantation. There was no difference in age, New York Heart Association functional class, QRS width before CRT and the rate of responders between patients with and without worsening FMR. Patients with worsening FMR had a tendency of larger left ventricular end-systolic dimension (58 [53-68] vs. 53 [47-60] mm, p&amp;lt;0.10), a significantly higher rate of female (38% vs. 19%, p&amp;lt;0.05) and a significantly larger left atrial volume index (LAVI) (63 [43-81] vs. 48 [35-62] ml/m2, p&amp;lt;0.05). By multivariate logistic regression analysis, female gender (odds ratio 4.3) and baseline LAVI (odds ratio 1.04 per a ml/m2 increase) were independent factors associated with worsening FMR. There was a significantly higher incidence of HF hospitalization (50% vs 15%, log-rank P&amp;lt;0.05) (Figure 1) and a higher incidence of VAs, defined as sustained ventricular tachyarrhythmias requiring implantable-cardioverter defibrillator therapy or external defibrillation, in patients with worsening FMR than patients without worsening FMR (65% vs 38%, log-rank P&amp;lt;0.05) (Figure 2). Multivariate analysis showed that worsening FMR was independently associated with the development of VAs (hazard ratio 2.77, 95% confidence interval 1.13-6.83). Conclusions In patients with HF and CRT, female gender and baseline LAVI were associated with worsening FMR after CRT. We need to pay attention to changes in the FMR that can be associated with developing VAs after CRT implantation.

Arrhythmogenic cardiomyopathy phenotype associated with the pathogenic founder variant c.1211dup in PKP2

Abstract Background Arrhythmogenic cardiomyopathy results in life-threatening ventricular arrhythmia and heart failure. Phenotypic features vary according to genetic aetiology. Genotype-phenotype research is therefore crucial for patient counselling and treatment decisions such as implantable cardioverter defibrillator therapy. By collecting data from patient records we characterized the clinical phenotype associated with variant c.1211dup (p.Val406Serfs*4) in the plakophilin-2 gene (PKP2), common in the Dutch population. Purpose We aimed to investigate the incidence of ventricular arrhythmia and heart failure in families carrying the PKP2 c.1211dup variant. Furthermore, we aimed to determine the founder status of this variant, and compare phenotype severity with other truncating PKP2 variants. Methods Clinical data were collected retrospectively from medical records of 106 PKP2 c.1211dup heterozygous carriers (&amp;gt;85% of known carriers in The Netherlands) in a Castor EDC database. Using occurrence of ventricular arrhythmia and heart failure, event-free survival was compared between males and females, and probands and family members, using log-rank tests. Using data from a central curated arrhythmogenic cardiomyopathy database, c.1211dup was compared to three other truncating PKP2 variants (c.235C&amp;gt;T (p.Arg79*), c.397C&amp;gt;T (p.Gln133*) and c.2489+1G&amp;gt;A (p.?)) on ventricular arrhythmia-free survival by a Cox proportional hazards model, corrected for sex and proband status. Results Forty-seven carriers (44%) were diagnosed with arrhythmogenic cardiomyopathy at 41 years on average. As shown in figure 1, 29 participants (27%) experienced episodes of ventricular arrhythmia and 12 (11%) developed heart failure, with male carriers showing significantly higher risks than females on both endpoints (p&amp;lt;0.05). Based on available magnetic resonance imagery and echocardiographic data, 46% of carriers showed either right ventricular dilatation and/or dysfunction, and a substantial minority of 37% showed some form of left ventricular involvement. Both geographical distribution of carriers (figure 2) and haplotype analysis suggested PKP2 c.1211dup to be a founder variant originating from the South-Western coast of the Netherlands. Finally, a Cox proportional hazards model suggested significant differences in ventricular arrhythmia-free survival between four PKP2 truncating founder variants, including c.1211dup. Conclusions The PKP2 c.1211dup variant is a Dutch founder variant associated with a typical right ventricular-dominant arrhythmogenic cardiomyopathy phenotype, but also notable left ventricular involvement. Males were most susceptible to the frequent ventricular arrhythmia, and less frequent heart failure was observed in general. Finally, c.1211dup possibly leads to a more severe phenotype than other Dutch PKP2 founder variants.Phenotype onset stratified by sexGeographic distribution carriers

Global Constructive Work is associated with ventricular arrythmias after cardiac resynchronization therapy

Abstract Aim Non-invasive left ventricular (LV) pressure-strain loops provide a novel method for quantifying myocardial work by incorporating LV pressure in measurements of myocardial deformation. Early studies suggest that myocardial work parameters such as Global Constructive Work (GCW) could be useful and reliable in arrhythmia prediction particularly in patients undergoing cardiac resynchronization therapy. The aim of this study was to evaluate whether the magnitude of GCW was associated with occurrence of ventricular arrhythmias in patients after cardiac resynchronization therapy. Method and results Patients on guideline-recommended treatment with a cardiac resynchronization therapy defibrillator (CRT-D) were evaluated by 2D speckle-tracking echocardiography including measurements of GCW at least six months after implantation. The primary outcome was a composite of appropriate defibrillator therapy and sustained ventricular arrhythmia under the monitor zone. A total of 162 patients (mean age 66 years (±10), 122 males (75%)), were included. 16 (10%) patients experienced the primary outcome during a median follow-up of 18 months (IQR: 12-25) after the index echocardiography. Patients with below-median GCW (&amp;lt;1,473 mmHg%) had a hazard ratio for the outcome of 8.14 [95% CI: 1.83-36.08], P=0.006 compared to patients above the median in a univariate model and remained an independent predictor after multivariate adjustment for eGFR and QRS duration (hazard ratio 4.75 [95% CI: 1.01 – 22.28], P&amp;lt;0.05. Conclusion In patients treated with CRT-D, GCW below median level was associated with a 5-fold increase in risk of ventricular arrhythmias.

Dose escalation for stereotactic arrhythmia radioablation of recurrent ventricular tachyarrhythmia - a phase II clinical trial

BackgroundStereotactic arrhythmia radioablation (STAR) is delivered with a planning target volume (PTV) prescription dose of 25 Gy, mostly to the surrounding 75–85% isodose line. This means that the average and maximum dose received by the target is less than 35 Gy, which is the minimum threshold required to create a homogenous transmural fibrosis. Similar to catheter ablation, the primary objective of STAR should be transmural fibrosis to prevent heterogenous intracardiac conduction velocities and the occurrence of sustained ventricular arrhythmias (sVA) caused by reentry. We hypothesize that the current dose prescription used in STAR is inadequate for the long-term prevention of sVA and that a significant increase in dose is necessary to induce transmural scar formation.ObjectiveA single arm, multi-center, phase II, dose escalation prospective clinical trial employing the i3 + 3 design is being conducted to examine the safety of a radiation dose-escalation strategy aimed at inducing transmural scar formation. The ultimate objective of this trial is to decrease the likelihood of sVA recurrence in patients at risk.MethodsPatients with ischemic or non-ischemic cardiomyopathy and recurrent sVA, with an ICD and history of ≥ 1 catheter ablation for sVA will be included. This is a prospective, multicenter, one-arm, dose-escalation trial utilizing the i3 + 3 design, a modified 3 + 3 specifically created to overcome limitations in traditional dose-finding studies. A total of 15 patients will be recruited. The trial aims to escalate the ITV dose from 27.0 Gy to an ITV prescription dose-equivalent level of maximum 35.1 Gy by keeping the PTV prescription dose constant at 25 Gy while increasing the dose to the target (i.e. the VT substrate without PTV margin) by step-wise reduction of the prescribing isodose line (85% down to 65%). The primary outcome of this trial is safety measured by registered radiation associated adverse events (AE) up to 90 days after study intervention including radiation associated serious adverse events graded as at least 4 or 5 according to CTCAE v5, radiation pneumonitis or pericarditis requiring hospitalization and decrease in LVEF ≥ 10% as assessed by echocardiography or cardiac MRI at 90 days after STAR. The sample size was determined assuming an acceptable primary outcome event rate of 20%. Secondary outcomes include sVA burden at 6 months after STAR, time to first sVA recurrence, reduction in appropriate ICD therapies, the need for escalation of antiarrhythmic drugs, non-radiation associated safety and patient reported outcome measures such as SF-36 and EQ5D.DiscussionDEFT-STAR is an innovative prospective phase II trial that aims to evaluate the optimal radiation dose for STAR in patients with therapy-refractory sVA. The trial has obtained IRB approval and focuses on determining the safe and effective radiation dose to be employed in the STAR procedure.Trial registrationNCT05594368.

Abstract 16984: A Wearable Device Reproducibly Identifies Premature Ventricular Contractions and Tachyarrhythmias in Heart Failure Patients

Introduction: occurrence of ventricular arrhythmias (VAs) has a dramatic impact on prognosis of patients with heart failure (HF). Hypothesis: wearable devices, including smartwatch (SW), might provide real-time informations in patients at risk of VAs. Aims: we therefore evaluated if SW detection of QRS interval width and voltage could reproducibly detect VAs and/or premature ventricular contractions (PVCs) in HF patients. Methods: HF patients (N=100) underwent continuous electrocardiographic (ECG) recordings through telemetry and SW during hospital admission. Left ventricular ejection fraction (EF) and laboratory pro-BNP levels assessments were obtained as well. Correlation of the ECG results was addressed using Pearson’s analysis for normally distributed data and Spearman’s analysis for non-parametric data. Bland-Altman was used for reliability between telemetry and SW ECG measurements. Results: mean EF was 45.92±12.12%; mean pro-BNP was 2826±5823 pg/mL. Using the SW and the ECG data, QRS width and voltage correlation coefficients were 0.990 (p&lt;0.001) and 0.974 (p&lt;0.001), respectively. Concordance was found between the two assessments for QRS width (bias, 0.20; SD 3.0; lower limit, –5.68; upper limit, 6.08), and voltage (bias, -0.029; SD, 0.611; lower limit, –1.227; upper limit, 1.169). Moreover, we found correlation coefficients of 0.964 (p&lt;0.001) and 0.970 (p&lt;0.001), respectively, for PVCs width and PVCs voltage using SW and telemetry or other ECG report. Similarly, both techniques showed positive concordance for PVCs width (bias, 0.368; SD, 2.65; lower limit, -4.83; upper limit, 5.56) and PVCs voltage (bias, 0.54; SD, 1.25; lower limit, -1.91; and upper limit, 2.996). Remarkably, VAs identification by the SW was reproducible and standardized. Conclusions: continuous monitoring through SW might be considered in HF patients upon discharge.

Glucose fluctuations aggravated the late sodium current induced ventricular arrhythmias via the activation of ROS/CaMKII pathway

BackgroundRecent evidence revealed that glucose fluctuation might be more likely to cause arrhythmia than persistent hyperglycemia, whereas its mechanisms were elusive. We aimed to investigate the effect of glucose fluctuation on the occurrence of ventricular arrhythmia and its mechanism. MethodsStreptozotocin (STZ) induced diabetic rats were randomized to five groups: the controlled blood glucose (C-STZ) group, uncontrolled blood glucose (U-STZ) group, fluctuated blood glucose (GF-STZ) group, and GF-STZ rats with 100 mg/kg Tempol (GF-STZ + Tempol) group or with 5 mg/kg KN93 (GF-STZ + KN93) group. Six weeks later, the susceptibility of ventricular arrhythmias and the electrophysiological dysfunctions of ventricular myocytes were evaluated using electrocardiogram and patch-clamp technique, respectively. The levels of reactive oxygen species (ROS) and oxidized CaMKII (ox-CaMKII) were determined by fluorescence assay and Western blot, respectively. Neonatal rat cardiomyocytes and H9C2 cells in vitro were used to explore the underlying mechanisms. ResultsThe induction rate of ventricular arrhythmias was 10%, 55%, and 90% in C-STZ group, U-STZ group, and GF-STZ group, respectively (P < 0.05). The electrophysiological dysfunctions of ventricular myocytes, including action potential duration at repolarization of 90% (APD90), APD90 short-term variability (APD90-STV), late sodium current (INa-L), early after depolarization (EAD) and delayed after depolarizations (DAD), as well as the levels of ROS and ox-CaMKII, were significantly increased in GF-STZ group. In vivo and ex vivo, inhibition of ROS or ox-CaMKII reversed these effects. Inhibition of INa-L also significantly alleviated the electrophysiological dysfunctions. In vitro, inhibition of ROS increase could significantly decrease the ox-CaMKII activation induced by glucose fluctuations. ConclusionsGlucose fluctuations aggravated the INa-L induced ventricular arrhythmias though the activation of ROS/CaMKII pathway.