Severe Ventricular Arrhythmias Research Articles

Premature ventricular contractions increase with heart rate in patients with mitral valve prolapse

Abstract Background A subset of patients with mitral valve prolapse (MVP) are at risk of life-threatening ventricular arrhythmias (VAs), and a high burden of premature ventricular contractions (PVCs) is associated with increased mortality in patients with MVP. Previous studies indicate that PVC burden could either increase with increasing heart rate (HR), decrease with increasing HR, or with no relationship to HR. The association between PVC burden and HR in MVP is not known, nor if there is an association with VAs. Purpose We aimed to explore the relationship between PVC burden and HR in patients with MVP. Furthermore, we aimed to explore whether the different PVC profiles were associated with severe VA. Methods In this cross-sectional ambispective outcome study, we included patients with MVP and available Holter monitorings with >100 PVCs per 24-hours seen at our tertiary centre. The Holter monitoring with the highest PVC burden was used in case of multiple recordings. We investigated the relationship between hourly PVC burden and hourly mean HR by univariable mixed linear regression. We defined PVC profiles as (1) fast-HR-dependent-PVC (F-HR-PVC) when there was a significant positive correlation, (2) slow-HR-dependent-PVC (S-HR-PVC) when there was a significant negative correlation, and (3) independent-HR-PVC (I-HR-PVC) when no correlation between PVC and HR was found. The significance was set to 0.05. Severe VA was defined as sustained ventricular tachycardia, non-sustained ventricular tachycardia with haemodynamic instability, ventricular fibrillation, aborted cardiac arrest, or appropriate shock by a primary preventive implantable cardioverterefibrillator. Severe VA was recorded from retrospective medical history, prospective ICD interrogation or monitoring with implantable loop recorder. Results We included 75 patients with >100 PVCs at Holter monitoring (median age 48 years [IQR 35-58], 58% female). The median PVC burden was 1.9% per 24-hours (IQR 0.4-7.2). We found F-HR-PVC in 49 patients (65%), S-HR-PVC in 1 (1%), and I-HR-PVC in 25 (33%). Twelve (16%) patients had severe VA and these had higher PVC burden compared to those without severe VA (7.3% per 24-hours [IQR 4.2-10.4] vs 1.1% per 24-hours [IQR 0.3-5.3], p=0.004). The median PVC burden was 1.5% (IQR 0.3-8.0) for F-HR-PVC, 5.7% for S-HR-PVC and 1.5% (IQR 0.3-8.0) for I-HR-PVC. We found no association between different PVC profiles and the presence of severe VA (F-HR-PVC 65% vs 67%, S-HR-PVC 2% vs 0%, I-HR-PVC 33% vs 33%, p>0.05 for all groups). Conclusion Fast-HR-dependent-PVC was most common in MVP patients, and slow-HR-dependent-PVC were rare. A higher PVC burden was associated with severe VA. However, different PVC profiles did not infer higher risk of severe VA in our study. Further studies are needed to explore whether distinct PVC profiles can predict severe VA in larger patient populations.

Analysis of long-term prognosis and risk factors in patients with dilated cardiomyopathy

Objective: To investigate the risk factors and long-term prognosis of major adverse cardiovascular events(MACEs) in patients with dilated cardiomyopathy (DCM). Methods: This study was a single-center retrospective cohort study. Clinical information from 300 patients with DCM hospitalized in Peking Union Medical College Hospital from April 2013 to April 2023 was collected. Based on echocardiography results, the patients were divided into two groups: isolated DCM and DCM with left ventricular non-compaction cardiomyopathy (LVNC). The MACEs, including major heart failure events, severe ventricular arrhythmias, and cardiovascular death, were recorded by outpatient or telephone follow-up. Univariate and multivariate Cox proportional hazard regression models were used to analyze the risk factors affecting the prognosis of patients with DCM. Kaplan-Meier curve and log-rank were used for survival analysis to compare the difference in the incidence of cardiovascular events between the two groups. Results: The included 300 DCM patients were (47.8±16.8) years old, with 197 males (65.7%), of which 237 (79.0%) were isolated DCM and 63 (21.0%) were DCM with LVNC. The follow-up time was 4.0 (1.9, 6.2) years. A total of 142 (47.3%) MACEs occurred, including 117 (39.0%) major heart failure events, 20 (6.7%) severe ventricular arrhythmia events, and 53 (17.7%) cardiovascular death events. Multivariate Cox proportional hazard regression analysis showed that increased left ventricular end-diastolic diameter (HR=1.21, 95%CI: 1.01-1.44, P=0.042), moderate or severe mitral regurgitation (HR=1.71, 95%CI: 1.19-2.47, P=0.004), increased ln (N-terminal pro-B-type natriuretic peptide) (HR=1.30, 95%CI: 1.10-1.54, P=0.002) were independent risk factors for dverse cardiovascular events in DCM patients, and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)/angiotensin receptor neprilysin inhibitor (ARNI) treatment (HR=0.45, 95%CI: 0.26-0.78, P=0.004) was independent protective factor. Kaplan-Meier survival analysis found no significant difference in the risk of MACEs between isolated DCM and DCM with LVNC (P=0.22). Similarly, there were no significant differences in the incidence of major heart failure, severe ventricular arrhythmia, and cardiovascular death between the two groups (all P>0.05). Conclusion: An increase in left ventricular end-diastolic diameter, moderate or severe mitral regurgitation, elevated N-terminal pro-B-type natriuretic peptide, and non use of ACEI/ARB/ARNI are independent predictors of cardiovascular events in DCM patients. There was no significant risk of MACEs in patients with isolated DCM and DCM with LVNC, and suggested that LVNC may be a unique phenotype and should be accurately managed in combination with genetic background.

Risk of Cardiovascular Events in Schizophrenic Patients Treated with Paliperidone Palmitate Once-Monthly Injection (PP1M): A Population-Based Retrospective Cohort Study in Taiwan.

Schizophrenia is one of the leading causes of disability. Paliperidone palmitate once-monthly injection (PP1M) was developed to provide consistent drug delivery and improve medication adherence for maintenance treatment. It is well known that patients with schizophrenia have higher cardiovascular risks, however little is known about the cardiovascular risks of patients with schizophrenia treated with PP1M in Asia. This study aimed to estimate the incidence of cardiovascular events after initiating PP1M treatment and evaluate the cardiovascular risk associations compared with oral second-generation antipsychotics (SGAs). Data from Taiwan's National Health Insurance Research Database were used to identify a cohort of adult patients with schizophrenia who received any SGAs from 1 March 2012 to 31 December 2018. Patients who initiated PP1M treatment were enrolled for descriptive analysis of incidence rates. PP1M patients were propensity matched 1:1 to patients initiating a new oral SGA, for comparative analysis based on demographics, clinical characteristics and treatment history at baseline, in three-step matching procedures, following the prevalent new-user design to enhance comparability. Follow-up ended at the end of the treatment episode of index drug, death, last record available, or end of the study (31 December 2019). Study endpoints included serious cardiovascular events (including severe ventricular arrhythmia and sudden death), expanded serious cardiovascular events (which further included acute myocardial infarction and ischemic stroke), and cardiovascular hospitalizations. Risks of study endpoints between matched cohorts were compared using Cox regression. Overall, 11,023 patients initiating PP1M treatment were identified (49.5% were females; mean age of 43.2 [12.2] years). Overall incidences for serious cardiovascular events, expanded serious cardiovascular events, and cardiovascular hospitalizations were 3.92, 7.88 and 51.96 per 1000 person-years, respectively. In matched cohort analysis (N=10,115), the hazard ratios (HRs) between initiating PP1M and a new oral SGA for serious cardiovascular events, expanded serious cardiovascular events, and cardiovascular hospitalizations were 0.86 (95% confidence interval [CI] 0.55-1.36), 0.88 (95% CI 0.63-1.21), and 0.78 (95% CI 0.69-0.89), respectively. This study reported the population-based incidence of cardiovascular events in schizophrenic patients initiating PP1M treatment. PP1M was not associated with increased risks of serious cardiovascular events but was potentially associated with lower risks of cardiovascular hospitalizations compared with oral SGAs.

Effect of liposomal bupivacaine for preoperative erector spinae plane block on postoperative pain following video-assisted thoracoscopic lung surgery: a protocol for a multicenter, randomized, double-blind, clinical trial.

There is still a controversy about the superiority of liposomal bupivacaine (LB) over traditional local anesthetics in postoperative analgesia after thoracic surgery. This study aims to determine the effect of LB versus bupivacaine hydrochloride (HCl) for preoperative ultrasound-guided erector spinae plane block (ESPB) on postoperative acute and chronic pain in patients undergoing video-assisted thoracoscopic lung surgery. This multicenter, randomized, double-blind, controlled trial will include 272 adult patients scheduled for elective video-assisted thoracoscopic lung surgery. Patients will be randomly assigned, 1:1 and stratified by site, to the liposomal bupivacaine (LB) group or the bupivacaine (BUPI) HCl group. All patients will receive ultrasound-guided ESPB with either LB or bupivacaine HCl before surgery and patient-controlled intravenous analgesia (PCIA) as rescue analgesia after surgery. The numeric rating scale (NRS) score will be assessed after surgery. The primary outcome is the area under the curve of pain scores at rest for 0-72 h postoperatively. The secondary outcomes include the total amount of opioid rescue analgesics through 0-72 h postoperatively, time to the first press on the PCIA device as rescue analgesia, the area under the curve of pain scores on activity for 0-72 h postoperatively, NRS scores at rest and on activity at different time points during the 0-72 h postoperative period, Quality of Recovery 15 scores at 72 h after surgery, and NRS scores on activity on postsurgical day 14 and postsurgical 3 months. Adverse events after the surgery are followed up to the postsurgical day 7, including postoperative nausea and vomiting, fever, constipation, dizziness, headache, insomnia, itching, prolonged chest tube leakage, new-onset atrial fibrillation, severe ventricular arrhythmia, deep venous thrombosis, pulmonary embolism, pulmonary atelectasis, cardiac arrest, ileus, urinary retention, chylothorax, pneumothorax, and organ failure. Analyzes will be performed first according to the intention to treat principle and second with the per-protocol analysis. We hypothesize that LB for preoperative ultrasound-guided ESPB would be more effective than bupivacaine HCl in reducing postoperative pain in video-assisted thoracoscopic lung surgery. Our results will contribute to the optimization of postoperative analgesia regimens for patients undergoing video-assisted thoracoscopic lung surgery.Clinical trial registration:http://www.chictr.org.cn, identifier ChiCTR2300074852.

473 Application of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) for modeling of Ankyrin-2 p.R990Q variant-induced ventricular arrhythmia and personalized medicine

OBJECTIVES/GOALS: The cytoskeletal protein α²II spectrin interacts with actin and ankyrin-2 in cardiomyocytes which is essential to orchestrate ion channels and membrane proteins in the cardiac dyad. Our goal is to understand molecular mechanism causing severe ventricular arrhythmias due to spectrin dysfunction and explore novel therapies to treat such conditions. METHODS/STUDY POPULATION: We previously published a case of a 36-year-old woman with an ankyrin-2 p.R990Q (ANK2) variant, presented with severe ventricular arrhythmias and sudden cardiac arrest, caused by a novel mutation in the ankyrin-B gene (c.2969G>A) that disrupts the interaction of ankyrin-B/βII spectrin. To model the condition, we will use human induced pluripotent stem cell (DF 19-9-7T, WiCell)-derived ventricular cardiomyocytes (iPSC-CMs) having ANK2 variant, engineered using CRISPR/Cas9 method (Synthego Corp.). We will validate the differentiation of iPSCs into ventricular lineage and characterize the ANK2 ventricular phenotype. Next, we will express light-gated cation channel Channelrhodopsin (ChR2) in the ANK2 iPSC-CMs and investigate the potential role of optogenetics in treating such severe arrhythmias. RESULTS/ANTICIPATED RESULTS: Immunostaining shows 87.339% of iPSC-CMs, treated with All-trans retinoic acid (RA) (1 uM) on days 7 and 12 [RA 7,12], and 23.84% of those, treated on days 3 and 5 [RA 3,5], expressed MLC-2V (p<0.001). Calcium reuptake (τ) is 0.5914 s in RA 7, 12 while 0.2247s in RA 3, 5 (p<0.001). APD90 and APD50 of RA 7, 12 are 2- and 5-fold higher than RA 3, 5, showing distinct ventricular and atrial phenotypes. Protein expression of βII-spectrin and ankyrin-2 and their co-localizations were reduced in the ANK2 phenotype compared to the healthy phenotype. We found prolongation of Ca2+ waves and τ with blue light on iPSC-CMs, expressing ChR2. We anticipate that such prolongation of calcium transients would prevent aberrant calcium spikes, rescue Ca2+/calpain-induced βII-spectrin loss and provide electrical stability. DISCUSSION/SIGNIFICANCE: Animal models cannot accurately recapitulate human cardiac electrophysiology. The proposed human iPSC-CM-based ANK2 model would provide better mechanistic insights of severe ventricular arrhythmias. Also, the proposed optogenetic cardioversion has the potential to provide safe, targeted and painless cardioversion to manage arrhythmias.

Prediction of severe ventricular arrhythmias in patients with mitral valve prolapse by exercise ECG

Prediction of severe ventricular arrhythmias in patients with mitral valve prolapse by exercise ECG

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.

Long QT syndrome induced by elevated dose of Fluoxetine Cloridrate: case report

Introduction: Long QT syndrome is a clinical condition that affects cardiac repolarization with an increased risk for the development of severe ventricular arrhythmias. The acquired form can be induced by drugs, such as selective serotonin reuptake inhibitors. Case report: E.A.C.G., female, 83 years-old, previously diagnosed with major depressive disorder in use of Fluoxetine the 80mg/day, was admitted in the emergency department after a syncopal event. An important widening of the QT interval was noted on the occasion, with a corrected value of 580ms. A 24-hour Holter monitoring showed increased ectopic ventricular activity (18% of beats), prolonged QT interval (up to 630 ms), and high-complexity ectopic ventricular beats. Non-sustained ventricular tachycardia was also observed (1030 episodes). The prolonged QT interval was associated to an elevated dose of Fluoxetine. Discussion: We believe that the coexistence between a high dose of Fluoxetine and other risk factor such as female sex and increased age contributed to the development of the case presentation. Conclusion: The rising prevalence of depression in the geriatric population and the indiscriminate use of antidepressive agents such as selective serotonin reuptake inhibitors may contribute to an increase in potentially severe cardiovascular complications.

Evaluation of the risk of sudden cardiac death in obstructive sleep apnea syndrome patients with Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio

Aims: Obstructive sleep apnea syndrome (OSAS) is a disorder characterized by recurrent collapse of the upper airway during sleep. OSAS is associated with an increased risk of cardiovascular morbidity and mortality. Tpeak to Trend (Tp-e) interval, the Tp-e interval/QT interval (Tp-e/QT) ratio, and the Tp-e interval/corrected QT interval (Tp-e/QTc) ratio, are associated with ventricular arrhythmias and sudden cardiac death in various disease groups. we aimed to investigate the relationship between changes in the new arrhythmia markers Tp-e interval, Tp-e/QT and Tp-e/QTc ratios in OSAS patients. Methods: The study looked at 45 people with OSAS (32 men) over the age of 18 and 43 healthy people (27 men) who were diagnosed with OSAS through polysomnography in a sleep lab. Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were calculated on the ECG. Results: The QT interval was shorter in the patient group than in the control group, in contrast to the QTc interval, which was comparable between groups (p = 0.006 and 0.810 in the patient and control groups, respectively). The Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio were significantly higher in PHPT patients included in the patient group compared to those included in the control group (p<0.01 in total). Conclusion: The Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were prolonged in OSAS patients. These findings suggest that OSAS patients may be predisposed to severe 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.

Social determinants of health and clinical outcomes among patients with atrial fibrillation: evidence from a global federated health research network.

Few studies have investigated the role of social determinants of health (SDoH) in patients with atrial fibrillation (AF). To investigate the relationship between SDoH and adverse events in a large multinational AF cohort. Retrospective study utilizing a global federated health research network (TriNetX). Patients with AF were categorized as socially deprived defined according to ICD codes based on three SDoHs: (i) extreme poverty; (ii) unemployment; and/or (iii) problems related with living alone. The outcomes were the 5-year risk of a composite outcomes of all-cause death, hospitalization, ischemic heart disease (IHD), stroke, heart failure (HF) or severe ventricular arrhythmias. Cox regression was used to compute hazard rate ratios (HRs) and 95% confidence intervals (CIs) following 1:1 propensity score matching (PSM). The study included 24 631 socially deprived (68.8 ± 16.0 years; females 51.8%) and 2 462 092 non-deprived AF patients (75.5 ± 13.1 years; females 43.8%). Before PSM, socially deprived patients had a higher risk of the composite outcome (HR 1.9, 95% CI 1.87-1.93), all-cause death (HR 1.34, 95% CI 1.28-1.39), hospitalization (HR 2.01, 95% CI 1.98-2.04), IHD (HR 1.67, 95% CI 1.64-1.70), stroke (HR 2.60, 95% CI 2.51-2.64), HF (HR 1.91, 95% CI 1.86-1.96) and severe ventricular arrhythmias (HR 1.83, 95% CI 1.76-1.90) compared to non-deprived AF patients. The PSM-based hazard ratios for the primary composite outcome were 1.54 (95% CI 1.49-1.60) for the unemployed AF patients; 1.39 (95% CI 1.31-1.47) for patients with extreme poverty or with low income; and 1.42 (95% CI 1.37-1.47) for those with problems related with living alone. In patients with AF, social deprivation is associated with an increased risk of death and adverse cardiac events. The presence of possible unmeasured bias associated with the retrospective design requires confirmation in future prospective studies.

Therapeutic measures for COVID-19 and their clinical relevance of hERG channel translocation: A Pharmacodynamic approach

The COVID-19 caused by SARS-CoV-2 poses a massive challenge to the medical system, especially the safe and effective COVID-19 treatment methods, forcing people to look for drugs that may have therapeutic effects as soon as possible. Some old drugs have shown clinical benefits after a few small clinical trials attracting significant attention. Clinically, however, many medications, including those currently shown to be effective against COVID-19, such as Chloroquine, hydroxychloroquine, azithromycin and lopinavir/ritonavir, may cause cardiotoxicity by acting on cardiac potassium channel, hERG channel due to their off-target effect. Blocking of hERG prolongs QT intervals on the electrocardiogram and thus might induce severe ventricular arrhythmias and even sudden cardiac death. Therefore, while focusing on the efficacy of COVID-19 drugs, the fact that they block hERG from causing arrhythmias cannot be ignored. To develop safe and effective drugs, it is necessary to understand the interactions between drugs and hERG channels and the molecular mechanism behind this high affinity. In this review, we focus on the biochemical and molecular mechanistic aspects of related drug blockade in the hERG, trying to provide insights into the QT interval prolongation caused by potential therapeutic drugs for COVID-19 and hope to weigh the risks and benefits when using related drugs.
 Keywords: COVID-19; Therapeutic measures; hERG channel; Pharmacodynamic; Vaccines

Risk of major cardiovascular events and bleeding in atrial fibrillation patients with chronic obstructive pulmonary disease treated with low dose azithromycin prophylaxis

Abstract Background Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of cardiovascular events in patients with atrial fibrillation (AF). Low Dose Azithromycin Prophylaxis (LDAP) is associated with improved outcomes in people suffering frequent exacerbations of COPD, but the widespread use of macrolides in patients with underlying cardiovascular disease has been debated due to safety concerns. Aims and Objectives To investigate the safety and efficacy of LDAP in AF patients with COPD in a large global federated dataset. Methods We conducted a retrospective cohort study within the global TriNetX Platform, including AF patients with COPD exacerbations. Risks for all-cause death, major adverse cardiovascular events (MACE: acute coronary syndrome, thromboembolic events, severe ventricular arrhythmias, and heart failure), intracranial hemorrhage (ICH) and gastrointestinal (GI) bleeding were recorded up to 30 days post-COPD exacerbations and compared between LDAP users (at least 3 months use and using LDAP at index) and an active control group (non-Azithromycin users receiving inhaled corticosteroids (ICS)). Cox regression analyses compared outcomes between groups after propensity-score-matching (PSM) for cardiovascular risk factors. Results We identified 2791 LDAP users with COPD and AF (mean age 71.5±10.6 years, 48.9% female), and 61054 controls. Before PSM, LDAP users showed a lower prevalence of cardiovascular risk factors and were less likely to be prescribed oral anticoagulation (68.1% vs 76.1%, p<0.001). After PSM no significant baseline differences were found between two groups. After COPD exacerbation, LDAP users were associated with a lower 30-day risk of all-cause death (HR: 0.72, 95%CI 0.60-0.97), MACE (HR 0.72, 95%CI 0.57-0.90), ICH (0.48, 95%CI 0.27-0.88) and GI bleeding (HR 0.69,95%CI 0.46-0.89) compared to the conventional treatment with ICS. Analysing the different time frames, the lower risk of thrombotic events was observed during the second week after COPD exacerbation while the magnitude of the bleeding risk reduction was more evident in the first 7 days (Figure 1). Conclusion LDAP use is associated with a lower risk of all-cause death, MACE and bleeding in AF patients with COPD. Further studies are needed to investigate the possible role of LDAP as part of the integrated care management of AF patients with COPD.

Sex differences in patients with acute myocarditis: a cohort study

Abstract Background Sex differences in patients with acute myocarditis (AM) are poorly understood. Purpose We aimed to study sex differences in AM patients including medical history, clinical presentations, diagnostics, and in-hospital outcomes. Methods We enrolled 215 patients with a diagnosis of AM at a tertiary hospital between January 2000 and December 2018 into a retrospective cohort study. All patients were hospitalized on an intensive care unit (ICU) with continuous monitoring. We compared sex differences in clinical presentation including ECG, prior medical history, cardiac biomarkers, cardiac imaging (echocardiography and cardiac MRI) and in-hospital outcomes including incident arrhythmia. Results Median age was 38 years and 27% were female. Overall, the most common presenting symptoms were chest pain (84%), dyspnea (34%) and fever (29%). Compared to men, women presented more often with dyspnea (47% vs 29%, p=0.015), were older (49 vs 36 years, p<0.001) and had more comorbidities including hypertension (33% vs 18%, p=0.032) and diabetes (14% vs 4%, p= 0.033). In the presenting ECG, female patients were more likely to present with T-wave inversion (46% vs 27%, p=0.017) and less likely with ST elevation (9% vs 39%, p<0.001) compared to male patients. The overall hospital stay was longer in women compared to men (7 vs 5 days, p=0.021) with no difference in the length of ICU stay (2.8 vs 3.0 days, p=0.782). Cardiac biomarkers including high-sensitivity troponin T (median 426 vs 665 ng/l, p=0.415) and CK-MB (median 23 vs 24 U/l, p=0.888) were not different, but women had higher NT-proBNP levels (median 2380 vs 353 ng/l, p=0.032). Left ventricular ejection fraction (LVEF) was similar between sexes, both by transthoracic echocardiography (55% vs 55%, p=0.864) and cardiac MRI (58% vs 56%, p=0.919). During monitoring, atrial fibrillation/atrial flutter occurred in 4% of patients, non-sustained ventricular tachycardia in 15%, sustained ventricular tachycardia in 4% and ventricular fibrillation/cardiac arrest in 2%. While we did not find a sex difference in atrial fibrillation/atrial flutter, women tended to have more severe ventricular arrhythmia (Figure). Conclusion Women constituted a quarter of our AM cohort. Compared to men, women were older at the time of AM diagnosis, had more comorbidities, showed different clinical and ECG findings, and were hospitalized longer. While LVEF was similar, women had higher levels of NT-proBNP.Central Illustration

Machine-learning score to predict in-hospital outcomes in patients Hospitalized in Intensive Cardiac Care Unit

Abstract Background While few scores are available for risk stratification of patients hospitalized in Intensive Cardiac Care Unit (ICCU) using traditional statistical methods, the potential benefit of machine learning is not established. Purpose To investigate the feasibility and accuracy of machine-learning (ML) to predict in-hospital major adverse events (MAE) in patients hospitalized in ICCU and compare its performance with existing scores. Methods From April 7 to 22, 2021, a French nationwide, multicenter, prospective, study involving 39 centers included all consecutive patients admitted in ICCU (N=1499). The primary outcome was in-hospital MAE defined as a composite outcome including all-cause in-hospital mortality, cardiogenic shock and resuscitated cardiac arrest (severe ventricular arrhythmia requiring defibrillation or anti-arrhythmic agents). Twenty-eight clinical, biological, ECG, and echocardiographic variables were considered for the Boruta variable selection algorithm. Using 31 centers randomly as an index cohort, several ML algorithms (logistic regression, ridge regression, boosted cost-sensitive C5.0 and XGBoost. C5.0 ) were evaluated to build a ML-score to predict in-hospital MAE. The other 8 centers formed the external validation cohort of the ML-score. Results Among 1499 consecutive patients included (age 63.3±14.9 years, 69.6% male), 61 had in-hospital MAE (4.3%). Out of 28 variables included in the feature selection, seven were selected as of particular importance to predict MAE in the training set (N=844) including: illicit drug use, mean arterial pressure, Killip stage, exhaled CO level, left ventricular ejection fraction, TAPSE value and peak E/e’ ratio. Boosted cost-sensitive C5.0 technique showed the best performance compared with other ML-techniques (area under the curve [AUC]=0.90, PR-AUC=0.57, F1 score=0.5), using 5 of the 7 above mentioned variables: mean arterial pressure, exhaled CO level, left ventricular ejection fraction, TAPSE value and peak E/e’ ratio. Our ML-score exhibited a higher AUC compared with existing scores for MAE prediction (ML score: 0.90 vs TIMI-score: 0.56, GRACE-score: 0.52, Acute HF-score: 0.65; all p<0.001). ML-score also exhibited a good AUC in the external cohort (AUC 0.97). Conclusions Including five simple clinical and echocardiographic variables (mean arterial pressure, exhaled CO level, left ventricular ejection fraction, TAPSE value and peak E/e’ ratio) routinely assessed in patients admitted in ICCU, the ML score exhibited a better prognostic value to predict in-hospital outcomes compared with existing scores.ML model and existing scores: ROC curveML model and existing scores: PR curve

Abstract 14684: Ambulatory Electrocardiogram for Mortality Risk Stratification in Arrhythmic Mitral Valve Prolapse

Introduction: Mitral valve prolapse (MVP) has been associated with sudden death. There is little data on whether ambulatory ECG monitoring can be used to better define risk. Hypothesis: Severity of ventricular arrhythmia (VA) on ambulatory ECG is associated with mortality in MVP patients. Methods: We studied patients aged 18 - 90 years with MVP on echocardiography between 2016-19 at our institution who underwent ambulatory ECG monitoring. Ambulatory ECGs were reviewed for PVC burden and rate of non-sustained ventricular tachycardia (NSVT). VA severity was classified as none (PVC<1% and no NSVT), mild (PVC>1% or NSVT<120 beats per minute [bpm]), moderate (NSVT 120-179 bpm) and severe (NSVT≥180 bpm). Kaplan-Meier survival analysis was used to assess whether VA severity is associated with mortality. Results: Holter monitoring was performed in 188 (29.5%) of 637 MVP patients. None, mild, moderate and severe VA was present in 91 (48.4%), 27 (14.4%), 56 (29.8%) and 14 (7.5%), respectively. On multivariate analysis of clinical and echocardiographic features, only bileaflet prolapse was associated with moderate to severe VA (odds ratio [95% CI], 2.10 [1.05-4.16, p=0.03). After a median (IQR) follow-up of 33 (19-46) months, 8 (4.2%) died. VA severity was positively associated with mortality (p=0.0189). Conclusions: Ventricular arrhythmia is frequently present in MVP. Increased severity of ventricular arrhythmia on ambulatory monitoring portends a worse prognosis in MVP patients. Ambulatory ECG monitoring should be considered for risk stratification in MVP patients.

Lifetime exercise dose and ventricular arrhythmias in patients with mitral valve prolapse.

Patients with mitral valve prolapse (MVP) have high risk of life-threatening ventricular arrhythmias (VAs). Data on the impact of exercise on arrhythmic risk in these patients are lacking. We explored whether lifetime exercise dose was associated with severe VA and with established risk factors in patients with MVP. Furthermore, we explored the circumstances at the VA event. In this retrospective cohort study, we included patients with MVP and assessed lifetime exercise dose as metabolic equivalents of task (MET) hours/week. Severe VA was defined as sustained ventricular tachycardia or fibrillation, aborted cardiac arrest, and appropriate shock by a primary preventive implantable cardioverter defibrillator. We included 136 MVP patients (48 years [interquartile range (IQR) 35-59], 61% female), and 17 (13%) had previous severe VA. The lifetime exercise dose did not differ in patients with and without severe VA (17 MET h/week [IQR 9-27] vs. 14 MET h/week [IQR 6-31], P = 0.34). Lifetime exercise dose > 9.6 MET h/week was a borderline significant marker for severe VA (OR 3.38, 95% CI 0.92-12.40, P = 0.07), while not when adjusted for age (OR 2.63, 95% CI 0.66-10.56, P = 0.17). Ventricular arrhythmia events occurred most frequently during wakeful rest (53%), followed by exercise (29%) and sleep (12%). We found no clear association between moderate lifetime exercise dose and severe VA in patients with MVP. We cannot exclude an upper threshold for safe levels of exercise. Further studies are needed to explore exercise and risk of severe VA.

Case report: A case of complete resolution of obstructive and central sleep apnea with Cheyne Stokes breathing in a patient with heart failure 60 days post-left ventricular assist device implantation

Sleep-disordered breathing (obstructive and central sleep apnea) are common in patients with heart failure with reduced ejection fraction. Herein, we report a 69-year-old patient with a history of severe heart failure and refractory ventricular arrhythmia who was diagnosed with a moderate degree of obstructive and central sleep apnea with Cheyne Stokes breathing. He underwent a successful implantation of left ventricular assist device. Our patient had a complete resolution of both obstructive and central sleep apnea 60 days post-LVAD implantation as confirmed by home sleep apnea test.

Transfusion-Related Hyperkalemia Causing Ventricular Arrhythmia in Neonatal Hepatectomy: A Critical Case Report

Transfusion-related hyperkalemia leading to ventricular arrhythmia is rare in neonates. We report a case of a 9-day-old neonate who developed severe hyperkalemia and ventricular arrhythmia after receiving a packed red blood cell transfusion during hepatectomy. After successful resuscitation, further transfusion was required. Subsequently, hyperkalemia was prevented by infusing packed red blood cells with saline in a ratio of 2:1, based on careful calculation.

Long-Term Prognosis of Different Subtypes of Left Ventricular Noncompaction Cardiomyopathy Patients: A Retrospective Study in China.

Left ventricular noncompaction (LVNC) is a heterogeneous cardiomyopathy that can be classified into different subtypes based on morphologic and functional features. However, the prognosis of the dilated and isolated subtypes of non-pediatric LVNC remains unknown. We retrospectively studied 101 patients with LVNC diagnosed at Peking Union Medical College Hospital from 2006 to 2022 using the Jenni criteria of transthoracic echocardiography. The patients were grouped into those with dilated LVNC (n = 64) or isolated LVNC (n = 37), and 88 patients (54 with dilated LVNC and 34 with isolated LVNC) were followed up successfully. The primary outcome was major adverse cardiovascular events (a composite of cardiovascular mortality, heart failure, severe ventricular arrhythmia, and systolic embolism). The median follow-up time was 5.24 years. The incidence of major adverse cardiovascular events was 43.2%; patients with dilated LVNC had a higher risk (adjusted hazard ratio, 4.43; 95% confidence interval, 1.24-15.81; p = 0.02) than those with isolated LVNC. None of the isolated LVNC patients had cardiovascular deaths or severe ventricular arrhythmias. The risk of systemic embolism was similar between patients with dilated and isolated LVNC. Our findings indicate that transthoracic echocardiography is a useful tool for classifying LVNC into subtypes with distinct clinical outcomes. Dilated LVNC is associated with a poor prognosis, while the isolated subtype is probably a physiological condition.