Cardiac Outcomes Research Articles

Current state of neurodevelopmental and psychosocial care practices for paediatric patients with ventricular assist devices: an Advanced Cardiac Therapies Improving Outcomes Network and Cardiac Neurodevelopmental Outcome Collaborative collaborative survey.

Paediatric patients with heart failure requiring ventricular assist devices are at heightened risk of neurologic injury and psychosocial adjustment challenges, resulting in a need for neurodevelopmental and psychosocial support following device placement. Through a descriptive survey developed in collaboration by the Advanced Cardiac Therapies Improving Outcomes Network and the Cardiac Neurodevelopmental Outcome Collaborative, the present study aimed to characterise current neurodevelopmental and psychosocial care practices for paediatric patients with ventricular assist devices. Members of both learning networks developed a 25-item electronic survey assessing neurodevelopmental and psychosocial care practices specific to paediatric ventricular assist device patients. The survey was sent to Advanced Cardiac Therapies Improving Outcomes Network site primary investigators and co-primary investigators via email. Of the 63 eligible sites contacted, responses were received from 24 unique North and South American cardiology centres. Access to neurodevelopmental providers, referral practices, and family neurodevelopmental education varied across sites. Inpatient neurodevelopmental care consults were available at many centres, as were inpatient family support services. Over half of heart centres had outpatient neurodevelopmental testing and individual psychotherapy services available to patients with ventricular assist devices, though few centres had outpatient group psychotherapy (12.5%) or parent support groups (16.7%) available. Barriers to inpatient and outpatient neurodevelopmental care included limited access to neurodevelopmental providers and parent/provider focus on the child's medical status. Paediatric patients with ventricular assist devices often have access to neurodevelopmental providers in the inpatient setting, though supports vary by centre. Strengthening family neurodevelopmental education, referral processes, and family-centred psychosocial services may improve current neurodevelopmental/psychosocial care for paediatric ventricular assist device patients.

Influence of Treatment Effect Modifiers in Fabry Disease: A Systematic Literature Review.

Fabry disease (FD) is a rare metabolic disorder which presents with considerable heterogeneity in disease characteristics. Given the absence of interventional studies comparing all available treatments, it is important for indirect treatment comparisons (ITCs) to account for potential treatment effect modifiers (TEMs). This systematic literature review (SLR) aimed to identify patient characteristics that may impact clinical outcomes by analyzing real-world evidence (RWE) in FD. An SLR was conducted according to PRISMA guidelines, with searches performed in the EMBASE, MEDLINE, and Cochrane databases (1946-2022; with a recent update in April 2023). Full-text articles reporting clinical outcomes from RWE studies of pharmacological therapies for the treatment of FD were included. Including studies from the recent SLR update, a total of 119 original studies met the PICOS criteria and 25 studies provided insights into TEMS. Potential TEMs in FD were identified: sex, age, timing of treatment initiation (early/delayed), left ventricular hypertrophy (LVH), estimated glomerular filtration rate (eGFR), proteinuria, presence of anti-drug-antibodies (ADAs) at baseline, and previous enzyme replacement therapy (ERT). In three studies (two including ERT-treated patients and one study of migalastat-treated patients) males showed worse renal outcomes than females. Five studies found that younger patients and those who received initial ERT before the age of 25years had greater reductions in plasma-lysoGb3, as well as more favorable renal, cardiac, and biochemical outcomes. Seven studies identified associations between LVH and reduced eGFR at baseline, along with an increased risk of cardiovascular, renal, and neurological events. In four studies, lower baseline eGFR and proteinuria were associated with faster annual eGFR decline despite ERT; high baseline proteinuria was a significant predictor of renal disease progression. Baseline ADAs were linked to lower eGFR, increased left ventricular mass, and reduced treatment impact on plasma/urine-lysoGb3. Migalastat was effective in treatment-naïve patients, while those previously treated with ERT experienced deteriorations in mean lysoGb3, eGFR, and left ventricular mass. This SLR highlighted several patient characteristics that influence treatment effectiveness in FD. It is important to account for these characteristics in ITCs to ensure unbiased outcomes.

Integrated Pacemaker System with Piezoelectric Energy Harvesting and Laser-Based Heartbeat Abnormality Detection

Cardiovascular diseases remain the leading cause of mortality globally, highlighting the critical need for innovative cardiac care technologies. This study presents an advanced pacemaker system integrating piezoelectric energy harvesting, chemical sensors, and laser-based heartbeat abnormality detection. By converting body thermal and mechanical energy into electrical power, the system ensures continuous operation. The integration of diode laser sensors provides non-invasive, real-time monitoring of blood flow and oxygen saturation, enabling early detection of arrhythmias. A mobile application supports remote monitoring and emergency alerts, enhancing patient safety. The system's novel architecture aims to reduce surgical interventions and improve cardiac outcomes, setting a benchmark for future advancements in biomedical engineering.

Why Portable Handheld Cardiac Ultrasound Devices Ought to Incorporate 3-lead Electrocardiographs: A Mini-narrative Review

Introduction: Transthoracic echocardiography is a non-invasive diagnostic test used to assess the structure and function of the heart in real-time. An examination of the heart's electrical activity is done non-invasively through electrocardiography (ECG). The ECG is primarily used during an echocardiography procedure to assess the heart's rhythm and to synchronise the cardiac cycles with echocardiographic image acquisition; this enables the echocardiographer to acquire images at specific phases of the cardiac cycle. A handheld echocardiograph is not connected to the electrocardiogram, which is a clinical limitation for the point-of-care ultrasound procedure. The objectives of this review are to highlight the reasons why 3-lead electrocardiography should be incorporated into pocket-sized handheld echocardiographs to support clinicians in conducting and reporting complete cardiac investigations. Methods: An in-depth search was made on the PubMed database to find experimental and review studies that assessed the importance of 3-lead ECG in the acquisition of hand-held echocardiographic data. Four related studies were selected for this review. Results: The study found that integrating cardiac point-of-care ultrasound into primary healthcare practices such as family medicine or general practitioners’ practices and training clinicians to accurately perform the procedure can expedite cardiovascular disease diagnosis and treatment in critical and non-critical scenarios. Secondly, recent hand-held cardiac ultrasound examination outcomes are as accurate and precise as standard transthoracic echocardiography and cardiac magnetic resonance imaging. Conclusion: Furthermore, medical device companies should consider integrating and producing new hand-held echocardiographs with configured 3-lead electrocardiographs that are artificial intelligence-enhanced to assist clinicians in precise point-of-care cardiac assessments.

Advances in Cardio-Oncology: The Emerging Role of Sglt2 Inhibitors in Cardioprotection

<i>Background: </i>The cardiotoxic effects of anti-tumor therapies represent a critical concern in oncology, as they compromise patient survival and quality of life by inducing cardiovascular diseases. With an increasing number of cancer patients undergoing treatments such as chemotherapy and radiation, the incidence of cardiotoxicity has surged. These adverse effects underscore the necessity of early detection, risk stratification, and preventive strategies tailored to mitigate cardiotoxicity and improve patient outcomes. <i>Objective: </i>This meta-analysis aims to systematically evaluate the effectiveness of various interventions designed to prevent or reduce cardiotoxicity associated with anti-tumor therapies. By synthesizing evidence from existing studies, we seek to identify the most effective measures, providing a comprehensive overview of the current landscape in cardioprotective strategies. <i>Methods: </i>We conducted a comprehensive literature search, including peer-reviewed studies that investigated preventive strategies for cardiotoxicity in patients undergoing anti-tumor therapy. Inclusion criteria were studies evaluating pharmacological and non-pharmacological interventions and their effects on cardiac function and patient outcomes. Data were extracted and analyzed to assess the impact of interventions on cardiotoxicity incidence, cardiac biomarkers, and clinical endpoints. <i>Main Findings: </i>Our analysis demonstrates a range of effective cardioprotective interventions, particularly focusing on beta-blockers, ACE inhibitors, and lifestyle modifications. Beta-blockers were found to reduce the incidence of left ventricular dysfunction, while ACE inhibitors showed promise in improving cardiac biomarkers. Additionally, lifestyle interventions, including exercise and dietary modifications, contributed to overall cardiovascular health, though further research is needed to define optimal protocols. <i>Conclusion: </i>Preventive strategies play a pivotal role in managing cardiotoxicity in cancer patients undergoing anti-tumor therapies. Pharmacological interventions, especially beta-blockers and ACE inhibitors, show significant potential in mitigating cardiac damage, while lifestyle interventions offer supplementary benefits. Our findings underscore the importance of an integrative approach, combining pharmacological and lifestyle modifications to protect cardiac function. Future research should focus on personalized cardioprotective protocols to optimize outcomes for cancer patients, ensuring that cardiovascular health is maintained alongside effective anti-tumor treatment.

Evaluating the Impact of Maternal Lipid Profiles on Fetal Cardiac Function at Mid-Gestation: An Observational Study

Background: Maternal dyslipidemia during pregnancy may influence fetal cardiac development and function, potentially predisposing offspring to cardiovascular diseases later in life. This study aims to evaluate the relationship between maternal lipid profiles and fetal cardiac function at mid-gestation, utilizing detailed echocardiographic assessments. Methods: In this prospective cohort study conducted at the Obstetrics and Gynecology Clinic of the Timișoara Municipal Emergency Hospital, 19 pregnant women aged 27–40 years were recruited and divided into two groups based on their triglyceride levels: Group A (triglycerides ≤ 150 mg/dL, n = 48) and Group B (triglycerides > 150 mg/dL, n = 28). Maternal demographic data and lipid profiles were recorded. Fetal echocardiographic measurements, including global longitudinal strain and ventricular function parameters, were obtained between 20 and 24 weeks of gestation. Statistical analyses, including subgroup comparisons, correlations, and regression analyses, were performed. Results: Maternal BMI was significantly higher in Group B compared to Group A (31.94 ± 2.80 vs. 27.01 ± 2.40 kg/m2, p < 0.001). Group B showed higher mean triglyceride levels (163.43 ± 11.34 mg/dL) compared to Group A (131.42 ± 10.57 mg/dL, p < 0.001). Fetal echocardiographic measurements indicated reduced global longitudinal strain in fetuses of Group B mothers (LV strain: −19.86% ± 6.83% vs. −26.14% ± 5.92%, p = 0.017). Significant correlations were found between maternal triglyceride levels and fetal LV strain (r = 0.536, p = 0.019). Regression analysis identified maternal triglyceride levels and BMI as significant predictors of reduced fetal LV strain (β = 0.45, p = 0.021 and β = 0.39, p = 0.038, respectively). Conclusions: Elevated maternal triglyceride levels, LDL cholesterol, and BMI are associated with altered fetal cardiac function parameters at mid-gestation, suggesting that maternal lipid profiles may impact fetal cardiac development. These findings underscore the importance of monitoring lipid levels during pregnancy and suggest potential benefits of managing dyslipidemia to improve fetal cardiac outcomes. However, the study included only a small sample; therefore, the study needs to be continued with a larger group.

Complex Attention-Deficit Hyperactivity Disorder in a 4-Year-Old With Repaired Critical Congenital Heart Disease and Autism Spectrum Disorder.

Congenital heart disease (CHD) is a risk factor for developmental delay and for attention-deficit hyperactivity disorder (ADHD). The Cardiac Neurodevelopmental Outcome Collaborative has developed recommendations for ongoing monitoring of this at-risk population to be able to detect developmental, learning, and behavioral concerns, as they become apparent as a child ages. A 4-year-old boy with tetralogy of Fallot with a ventricular septal defect repaired in infancy was followed periodically in the cardiac neurodevelopmental follow-up clinic and diagnosed with autism spectrum disorder as well as additional developmental and medical issues. He received early childhood special education and therapeutic interventions as well as social skills training and applied behavior analysis. At age 4 years, Alex presented with symptoms of hyperactivity, inattention, impulsivity, and immediate safety concerns for elopement. The clinician diagnosed him with ADHD-combined type. He was recommended to start medication in addition to behavioral and developmental supports. Managing medications in a child with CHD and ADHD presents unique challenges, and medication decisions were carefully made in collaboration with the child's cardiologist. After some medication adjustments and ongoing behavioral therapy to address behaviors associated with ADHD and autism spectrum disorder, the child is doing well academically and socially. Attention-deficit hyperactivity disorder medications can be safely prescribed in patients with CHD. However, pharmacotherapy for co-occurring ADHD and CHD needs an additional level of oversight and collaboration between cardiology and prescribing clinicians. Behavioral therapies can be transdiagnostic and address challenges associated with autism and symptoms related to ADHD.

Effect of a patient health engagement (PHE) model on rehabilitation participation in patients with acute myocardial infarction after PCI: a study protocol for a randomized controlled trial

BackgroundParticipation in cardiac rehabilitation is low in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). Although existing rehabilitation methods have achieved certain results, patient participation in exercise rehabilitation is not ideal. The Patient Health Engagement (PHE) model is designed to ensure that patients improve their participation in cognitive, emotional, behavioral, and other aspects in all phases of exercise rehabilitation. The purpose of this study is to confirm whether the rehabilitation method based on the PHE model improves the rate of patient participation and enhances the rehabilitation effect during cardiac rehabilitation in patients with acute myocardial infarction compared with the traditional rehabilitation model.Methods/designThis is a single-center, double-blind, randomized, controlled trial that will enroll 128 patients. Patients with stable acute myocardial infarction after undergoing PCI who received cardiac rehabilitation and postoperative LVEF ≥ 40%, categorized into Killip class I ~ II and with age ≥ 18 years, will be included in the study. Exclusion criteria are mainly malignant arrhythmias, acute heart failure, congestive heart failure, and patients requiring intra-aortic balloon counterpulsation. Patients will be randomized in a 1:1 ratio to the intervention (1) and control (2) groups. Physicians, rehabilitation specialists, patients, and data collectors will be blinded during the study. A rehabilitator and a specialist nurse will conduct the cardiac rehabilitation. The specialist nurse will hand over the sealed bag containing patient information (group 1 or 2) to the physician. Group 1 will undergo cardiac rehabilitation through the PHE model, three times a week for 3 months. The rehabilitation program will be evaluated and adjusted in time from each period of the rehabilitation. Group 2 will be treated with routine cardiac rehabilitation. The rehabilitation participation rate of the two groups will be evaluated before and after 3 months of intervention. The primary outcome will be the level of patient participation in rehabilitation, and the secondary outcome will include general data of patients, postoperative rehabilitation indicators, cardiac rehabilitation knowledge–attitude–practice questionnaire, cardiovascular adverse events, and a brief mood scale.Expected outcomesWe expect improved cardiac rehabilitation participation rates and rehabilitation outcomes in patients with acute myocardial infarction after undergoing PCI using the PHE model.DiscussionThis approach may increase patient participation in rehabilitation, improve rehabilitation outcomes, and be widely implemented in hospitals and rehabilitation centers.Trial registrationClinicalTrials.gov identifier, ChiCTR2400085276 (Version 2.0 June 04, 2024), https://www.chictr.org.cn.Trial sponsorShandong Second Medical university, Weifang, Shandong. Contact name: Dechun Qin, Address: Shandong Second Medical university, Weifang Shandong. Email: 13562666589@163.com.

Ceramides as Biomarkers of Cardiovascular Diseases and Heart Failure.

Ceramides are lipid species that play several physiological roles in the body, including stress response, inflammation, and apoptosis, and their involvement in lipid metabolism and energy production makes them crucial in the pathophysiology of heart failure (HF). Several species of ceramides and ceramide signatures have recently been investigated as possible biomarkers of cardiovascular disease (CVD), and risk scores have demonstrated prognostic value in stratifying patients by risk and possibly predicting adverse cardiac events. With growing interest in targeting metabolic dysfunction, understanding the role of ceramides in CVD also opens the possibility of novel therapeutics that target ceramide metabolism to improve cardiac function and cardiac outcomes in patients. Understanding the role of ceramides in CVD opens the possibility of novel diagnostics and theragnostic targeting ceramide metabolism to improve cardiac function and cardiac outcomes in patients with heart failure.

A US payer budget impact analysis of Flurpiridaz-PET-MPI compared to SPECT-MPI in the diagnosis of coronary artery disease

Aims This economic model was developed to assess the budget impact of a novel radiotracer, Flurpiridaz (F18-PET-MPI), compared to SPECT-MPI from a US payer perspective. Materials and Methods The model was developed comparing F18-PET-MPI and SPECT-MPI, with F18-PET-MPI modality share increasing from 0.5% to 2.5% of the total MPI modality share, over a 5-year time horizon. The model estimates the impact of diagnostic performance on downstream healthcare resource utilization (HCRU) including invasive coronary angiography (ICA), revascularization, pharmacological treatment, and cardiac outcomes (CO) such as cardiac mortality (CM) and myocardial infarction (MI). Four suspected CAD populations, including general and difficult-to-image subgroups, were analyzed. Clinical inputs used to support the parameterization of the model were sourced from a systematic literature search and included claims-based real-world evidence, observational, and multicenter registry studies to inform the rates of HCRU and CO, and head-to-head comparative clinical trial data advised diagnostic performance inputs. Reimbursement codes informed MPI modality costs. Results are reported as per-member per-month (PMPM) based on a hypothetical health plan. Results In all suspected CAD populations analyzed, there was a nominal cost increase in the world with F18-PET-MPI. The 5-year average PMPM incremental budget impact ranged from $0.02 to $0.05 across all suspected CAD subgroups. Cost-savings were associated with decreased downstream CO such as CM, MI, and ICA. Limitations and Conclusion The available literature to source all parameters in the model was limited; therefore, assumptions and additional calculations were made based on published evidence to inform the model. A one-way sensitivity analysis was performed to confirm and address uncertainty in key parameters. This comprehensive analysis illustrates that the superior diagnostic performance of F18-PET-MPI may result in reduced adverse CO events and associated costs, increased appropriate identification and treatment of CAD, and a minimal increase in overall costs among general and difficult-to-image patient subgroups.

The Use of Antioxidants for Cardiovascular Protection in Fetal Growth Restriction: A Systematic Review.

Fetal growth restriction (FGR) increases the risk of cardiovascular disease. There are currently no treatment options available; however, antioxidants have shown potential to improve cardiovascular deficits associated with FGR. This systematic review aimed to determine whether antenatal antioxidant intervention can effectively protect the developing cardiovascular system in FGR. We searched for interventional studies that used an antenatal antioxidant intervention to improve cardiac and/or vascular outcomes in FGR published between 01/1946 and 09/2024 using MEDLINE and Embase (PROSPERO: CRD42024503756). The risk of bias was assessed with SYRCLE. The studies were assessed for cardiovascular protection based on the percentage of cardiac and/or vascular deficits that were restored with the antioxidant treatment. Studies were characterised as showing strong cardiovascular protection (≥50% restoration), mild cardiovascular protection (>0% but <50% restoration), an antioxidant-only effect (this did not include control group which showed a change with antioxidant intervention compared to FGR) or no cardiovascular protection (0% restoration). Thirty-eight publications met the inclusion criteria, encompassing 43 studies and investigating 15 antioxidant interventions. Moreover, 29/43 studies (71%) reported the restoration of at least one cardiac or vascular deficit with antioxidant intervention, and 21/43 studies (51%) were classified as strong cardiovascular protection. An ex vivo analysis of the arterial function in seven studies revealed endothelial dysfunction in growth-restricted offspring and antioxidant interventions restored the endothelial function in all cases. Additionally, four studies demonstrated that antioxidants reduced peroxynitrite-mediated oxidative stress. Notably, only 13/43 studies (32%) delayed antioxidant administration until after the induction of FGR. Antenatal antioxidant interventions show promise for providing cardiovascular protection in FGR. Melatonin was the most frequently studied intervention followed by nMitoQ, vitamin C and N-acetylcysteine, all of which demonstrated a strong capacity to reduce oxidative stress and improve nitric oxide bioavailability in the cardiovascular system of growth-restricted offspring; however, this systematic review highlights critical knowledge gaps and inconsistencies in preclinical research, which hinder our ability to determine which antioxidant treatments are currently suitable for clinical translation.

Right atrial strain measured by 2D speckle-tracking echocardiography is associated with poor cardiac outcomes in patients with heart failure.

Right heart failure (HF) is a poor prognostic factor in patients with HF. The right atrial (RA) function has attracted less attention than the right ventricular (RV) function. The association of RA reservoir strain evaluated by 2D speckle-tracking echocardiography (2DSTE) with clinical outcomes in patients with HF remains unclear. We prospectively enrolled patients with HF admitted to our hospital. We measured the RA, RV, left atrial (LA), and left ventricular (LV) strain using 2DSTE before discharge. The RA reservoir strain (RASr) was measured in the global right atrium. The primary endpoints were cardiac death and worsening of HF requiring rehospitalization or intravenous diuretics. Among 226 patients with HF, 72 primary endpoints were recorded during a median follow-up period of 1081days. Kaplan-Meier analysis showed a higher cardiac event rate in the low RASr group than in the high RASr group (P = 0.0089). Multivariate Cox hazard analysis showed that RASr was independently associated with cardiac events after adjusting for confounding factors [hazard ratio (HR) 0.71; 95% confidence interval (CI) 0.51-0.96; P = 0.0347]. Decreased RASr could be a feasible marker of cardiac events in patients with HF.

Analysis of the Influence of Personality Traits on the Level of Knowledge and Health Behaviours of Cardiac Patients.

Background/Objectives: Numerous risk factors of cardiac diseases are influenced by health behaviours. An individual's health behaviours, somatic symptoms and even cardiac outcomes can be influenced by their personality. The aim of this study was to analyse the influence of personality traits on the knowledge and health behaviour of cardiac patients. Methods: The study was conducted at the Independent Public Voivodship Hospital in Szczecin on 180 patients in the invasive cardiology wards and the intensive cardiac care unit between July and September 2019. A self-developed questionnaire and the NEO-Five-Factor Inventory-3 (NEO-FFI) and Health Behaviour Inventory (HBI) standardised tools were used. Results: Respondents mostly linked the occurrence of cardiovascular disease with smoking (87.22%) and hypertension (85.56%). A large majority of the respondents (68.44%) knew the correct recommended values for blood pressure. This was also the case for total cholesterol-only 20.56% of the patients did not know the correct levels. Respondents experienced more difficulty in adhering to preventive measures-only 27.22% followed a low-fat diet and only half controlled their weight. The overall HBI scale score was 5.93 sten, which indicates an average score. The most intense personality trait among the respondents was extraversion (5.79), while the least intense was agreeableness (4.12). Neuroticism was found to be negatively correlated (p < 0.05) with healthy eating habits and a positive mental attitude. Extroverts, on the other hand, are more likely to take preventive action. Older and non-working individuals are more likely to exhibit health-promoting behaviours in all HBI categories (p < 0.05). Conclusions: The personality traits that have the greatest impact on health behaviour are extraversion, agreeableness and conscientiousness. Health practises also depend on gender, age and work activity. Further research on more diverse groups is needed.

Utilisation of the National Early Warning Score (NEWS) and Assessment of Patient Outcomes Following Cardiac Surgery.

Objectives: The national early warning score (NEWS) was introduced to improve the detection of, and standardise the assessment of, the severity of acute illness in the National Health Service (NHS). We assessed whether the recommended threshold trigger score of 5 or more in a Critical Care Outreach Team (CCOT) review could accurately predict patients at risk of deterioration following cardiac surgery and patient outcomes. Methods: We investigated adult cardiac surgery patients between October 2019 and December 2021. NEWS 2 parameters triggering CCOT referrals and NEWS 2 parameters < 5 versus ≥5 were compared, and the resulting patient outcomes were evaluated. Results: Over this period, 3710 patients underwent surgery, of whom 162 (4.4%) initiated 193 calls to the CCOT. The mean number of NEWS 2 parameters on CCOT activation was 6.14 ± 2.43 (NEWS 0-16); 34 (20.98%) activations were from patients with NEWS 2 < 5. Low oxygen saturation (SpO2) (59.3%) and oxygen therapy (83.3%) were the most common physiological parameters raising the score. CCOT activations led to 38 transfers from the ward to the high-dependency unit (HDU) and 18 transfers to the intensive therapy unit (ITU). Cardiac arrest calls were initiated in 12 (7.40%) patients and two culminated in death. Fourteen (8.64%) had emergency resternotomy. The in-hospital mortality rate was 10.5% (17/162) in patients referred to CCOT versus 3.9% (139/3548) in patients who were not (p < 0.001). The in-hospital mortality in patients with NEWS 2 < 5 vs. NEWS ≥ 5 was 17.6% (6/34) versus 8.6% (11/128) (p = 0.126). Conclusions: There was no difference in in-hospital mortality in patients below or above a NEWS 2 of 5, but there was a significant difference in in-hospital mortality in patients reviewed by the CCOT (p < 0.001). Tailoring the threshold score specifically for the cardiac surgical cohort, in conjunction with clinician involvement, may improve outcomes.

Abstract 4137620: Serum Acylcarnitines Predict Longitudinal Deteriorations in Cardiac Function and Adverse Outcomes in Older Adults

Background: Circulating acylcarnitines (ACs), biomarkers of mitochondrial β-oxidative function, are linked to cardiovascular diseases (CVD) yet the extent to which ACs relate to prospective cardiac aging remains uncertain. We investigate the longitudinal associations between ACs, cardiac function, and clinical outcomes. Methods: A population-based sample of community older adults without CVD underwent baseline serum metabolomic profiling and interval echocardiography at five years. Incident hospitalizations were prospectively tracked from 2014 to 2021. Multiple linear regression adjusted for significant clinical variables. Results: Of 202 participants (baseline 65±11.9 years, 49.3% women), we observed interval increases in risk factors (hypertension 39% vs 52.2% p&lt;0.001; dyslipidemia 39% vs 50% p=0.034; diabetes 11.7% vs 18.8% p=0.035; smoking 13.2% vs 24.7% p=0.003; waist circumference 81±10.1 vs 86±9.9cm p&lt;0.001) during follow-up (4.9±0.4 years). These changes paralleled E/e’ increases (8.9±2.6 vs 11.1±3.3 p&lt;0.001) and E/A decreases (1.09±0.4 vs 1.0±0.4 p&lt;0.001). Baseline C8:1 (β=0.182 p=0.011), C22:3 (β=0.148 p=0.047), C22:5 (β=0.210 p=0.003), C5:1 (β=-0.142 p=0.048), and C16-OH (β=-0.156 p=0.028) levels were associated with E/e’ change over time while C6 (β=0.163 adj. p=0.019), C8:1 (β=0.137 adj. p=0.047), C10:2 (β=0.153 adj. p=0.035), C14:3 (β=0.147 adj. p=0.031), and C16:1-OH/C14:1-DC (β=0.158 adj. p=0.022) were associated with E/A change. At follow-up, baseline C8:1 (β=0.178 adj. p=0.006) and C10:3 (β=0.145 adj. p=0.024) were associated with E/e’ while C4-DC/C6-OH (β=-0.004 adj. p=0.034) was associated with E/A. Baseline C22:2 predicted incident hospitalizations (HR=1.20 95%CI 1.03-1.39, adj. p=0.018). Conclusion: Circulating ACs independently predicted declining cardiac function and adverse outcomes over five years among older adults without CVD. The prognostic effect of ACs should be translated to strategies targeting mitochondrial health in cardiac aging prevention.

Abstract 4137534: Troponin Can Predict Late Gadolinium Enhancement on Cardiac MRI in COVID-19 Vaccine-Associated Myocarditis

Background/Aim: We previously reported that late gadolinium enhancement (LGE) on cardiac MRI (CMR) was as high as 82% in pediatric patients with COVID-19 vaccine-associated myocarditis (C-VAM) despite mild clinical symptoms and normal left ventricular function. As LGE can be a harbinger for future adverse events including arrhythmias, heart failure or sudden cardiac death, we sought to identify predictors for LGE in C-VAM, specifically assessing troponin as a screening marker for C-VAM patients at risk for myocardial scarring who could then be referred for a confirmatory CMR with LGE. Methods: In this longitudinal multicenter retrospective observational study across 38 U.S. member institutions of the M yocarditis A fter C OVID V accination (MACiV) study network, 333 patients with C-VAM based on CDC criteria were included from April 2021 to November 2022. Data collected included demographics, laboratory values, clinical and cardiac imaging characteristics and outcomes. Using logistic regression, troponin levels at presentation were assessed as a log transformed continuous variable and categorized into tertiles. Results: The C-VAM patients were predominantly white (67%) adolescent males (91%, 15.7± 2.8 years). There were 216/333 (65%) patients who had both a reported troponin value and had a CMR. On univariate analysis, elevated troponin increased the probability of having LGE (OR=1.29, 95% CI: 1.06, 1.58, p=0.012). Even after controlling for age, race, sex, number of vaccine doses and left ventricular ejection fraction (OR=1.32, 95% CI: 1.06, 1.65, p=0.013). Patients &gt;15 years compared to those ≤15 years of age were 2.94 (95% CI: 1.28, 6.75, p=0.011) times more likely to have LGE at presentation. Patients with troponin levels in the highest tertile compared to lowest tertile were 2.66 times (95% CI: 1.04, 6.83, p=0.042) more likely to have LGE along with a greater involvement &gt; 4 AHA myocardial segments with LGE (p=0.004) Conclusions: Higher troponin values are associated with presence of late gadolinium enhancement on cardiac MRI in patients with COVID-19 vaccine-associated myocarditis. Troponin levels at presentation may facilitate risk stratification and function as a screening tool to identify those C-VAM patients with the greatest likelihood of myocardial scarring, who may benefit from undergoing CMR for tissue characterization.

Abstract 4114505: Cardiovascular Adverse Events After Anti-BCMA CAR-T (Ide-Cel and Cilta-Cel) for Relapsed/ Refractory Multiple Myeloma

Introduction: Idecabtagene vicleucel (Ide-Cel) and ciltacabtagene autoleucel (Cilta-cel) are novel CAR-T therapies targeting B-cell maturation antigen (BCMA) and approved for relapsed and refractory multiple myeloma (RRMM). While cardiovascular adverse events (CVAE) are relatively common with CD-19 CAR-T, the incidence of CVAE in the real-world setting for anti-BCMA CAR-T in RRMM is largely unknown. This study aims to determine the incidence of CVAE and its associated risk factors in patients treated with ide-cel and cilta-cel. Method: This single-center retrospective cohort study evaluated RRMM patients treated with ide-cel and cilta-cel from May 2021 to December 2023. We assessed baseline cardiac and oncologic characteristics and clinical outcomes post-CAR-T. Cytokine release syndrome (CRS) and immune cell-associated neurologic syndrome (ICANS) grading followed ASTCT consensus guidelines. Result: A total of 164 RRMM patients treated with ide-cel (N=109) or cilta-cel (N=55) with at least 6 months follow-up were included. The average age was 63 years, and 57% were male. Advanced RRMM stage (R-ISS III) was present in 17% with a median of 6 prior lines of therapy. CRS grade equal or greater than 2 occurred in 22%, and ICANS grade equal or greater than 3 in 6.7%. Twenty patients (12.2%) experienced CVAE, including atrial fibrillation (7.9%), non-sustained ventricular arrhythmia (3.0%), heart failure (3.7%), and cardiovascular death (0.6%). R-ISS III was associated with increased CVAE (52.9% vs. 11.5%; P=0.001). Patients with CVAE had higher baseline ferritin and CRP levels and a higher incidence of CRS grade ≥ 2 (60% vs. 16.7%; P&lt;0.001) and ICANS grade ≥ 3 (20% vs 4.9%; P=0.001). Treatment with tocilizumab, steroids, or anakinra was more common in patients with CVAE. Conclusion: CVAE occurred relatively frequently following BCMA CAR-T therapy, with high-grade CRS identified as a consistent risk factor. Most CVAEs were manageable with appropriate supportive care, including careful observation and active treatment of CRS.

Bystander Response and Out-of-Hospital Cardiac Arrest Outcomes (Bro. Study) in 3 Gulf Countries: Protocol for a Prospective, Observational, International Collaboration Study.

: Globally, there is significant variation in the out-of-hospital cardiac arrest (OHCA) survival rate. Early links in the chain of survival, including bystander cardiopulmonary resuscitation (CPR) and the use of an automated external defibrillator at the scene, are known to be of crucial importance, with strong evidence of increased survival rate with good neurological outcomes. The data from the Middle East are limited and report variable rates of bystander CPR and survival. It is crucial to get prospective, reliable data on bystander response in these regions to help plan interventions to improve bystander response and outcomes. This international collaborative study aims to describe the characteristics, including bystander interventions and outcomes, of OHCAs brought to hospitals enrolled in the study from Abu Dhabi, United Arab Emirates; Doha, Qatar; and Muscat, Oman. It also aims to describe the strength of the association between bystander response and OHCA outcomes, including the return of spontaneous circulation, survival to hospital admission, survival to discharge, and good neurological outcome at discharge in the local context of low bystander CPR rates. This multicenter, prospective, noninterventional observational study (Bro. Study) will be conducted at the emergency departments of 4 participating tertiary care hospitals in 3 countries. The data will be collected prospectively according to the Utstein style (a set of internationally accepted guidelines for uniform reporting of cardiac arrests) on demographic variables (age, sex, nationality, country, participating center, and comorbidities), peri-cardiac arrest variables (location, witnessed or not, bystander CPR, use of automated external defibrillator, time of emergency medical services arrival, initial rhythm, number of shocks, and time of prehospital CPR), and outcome variables (return of spontaneous circulation, survival to discharge, and neurological outcome at discharge and 3 months). Univariate and multivariate analysis with logistic regression models will be used to measure the strength of the association of bystander interventions with outcomes using SPSS (version 22). Data collection began in November 2023 and will continue for 2 years, with publication expected by early 2026. Bystander response to an OHCA is critical to a favorable outcome. The reliable, baseline bystander CPR data will be a cornerstone in the team's next planned projects, which are to qualitatively identify the barriers to bystander CPR, conduct a scoping review of community interventions in the Gulf and other Asian countries, and design and implement strategies to help improve the bystander CPR rate in the community. DERR1-10.2196/58780.

Abstract 4122257: Inhibition of Neutrophil Extracellular Traps Prevents Heart Failure by Preserving Mitochondrial Function of Cardiomyocytes in Mice

Background: We have previously demonstrated that neutrophil extracellular traps (NETs) in myocardial tissue are associated with cardiac dysfunction and adverse outcomes in patients with heart failure with reduced ejection fraction. Here, we aimed to elucidate the underlying mechanisms and to clarify whether inhibiting NETs could rescue the cardiac phenotype using ex vivo and in vivo models. Methods and Results: Given that peptidyl arginine deiminase 4 (PAD4) is essential for the formation of NETs, PAD4 knockout mice were used for this study. First, we assessed the mitochondrial function of cardiomyocytes by conducting real-time measurements of the oxygen consumption rate in ex vivo . Extracellular flux analysis revealed that NETs-containing conditioned medium from wild-type neutrophils or purified NET components led to impaired mitochondrial oxygen consumption of adult mouse cardiomyocytes, while these effects were abolished when PAD4 in neutrophils was genetically ablated (Figure 1). In a murine model of pressure overload-induced heart failure, transverse aortic constriction (TAC) operation was performed on wild-type and PAD4 knockout mice. Immunohistological analysis demonstrated that TAC induced the formation of NETs in the myocardium, with the greatest number of NETs occurring at 1 day, persisting into the failing stage at 4 weeks in wild-type mice, while PAD4-deficient hearts displayed no presence of NETs in the heart tissue (Figure 2). Four weeks after TAC, left ventricular ejection fraction was reduced in wild-type mice, whereas PAD4 knockout mice displayed preserved left ventricular ejection fraction (Figure 2). Finally, we investigated the bioenergetics of cardiomyocytes isolated from PAD4 knockout mice after TAC. Maximal mitochondrial oxygen consumption rate in cardiomyocytes isolated from TAC-operated PAD4 knockout mice was significantly higher than in those from TAC-operated wild-type mice (Figure 3). Conclusion: Our data suggest that NETs directly derived impairment of mitochondrial function in cardiomyocytes. Inhibiting NETs represents a potential therapeutic approach for heart failure, preventing mitochondrial dysfunction of cardiomyocytes.

Abstract 4115235: Disparities in Youth Cardiac Screening by Childhood Opportunity Index: Insights from the Heartbytes Database

Intro: The AHA endorses screening youth athletes to identify risk for sudden cardiac arrest (SCA). Rates of SCA can be predicted by social determinants of health (SDOH) such as education level and proportion of Black residents in ZIP Code. The Child Opportunity Index (COI) quantifies neighborhood factors that influence health and development. The link between COI and youth cardiac screening findings and outcomes remains unclear. Hypothesis: Cardiac screening data will differ significantly by COI. Aims: To identify differences in cardiac screening data in children of varying COI. Methods: The HeartBytes Database, including sports exams, self-reported physical activity (PA), and zip codes from Simon's Heart screenings was augmented with COI index zip code data. Chi-squared and logistic regression were used to analyze demographics, cardiac risk factors, and screening results. Data: Screening data of 11,431 youth athletes (median age 14.3 (IQR = 3), BMI 20.6 (4.8), 53.7% male, 70.6% White) was analyzed. The majority of children had very high overall COI (Figure 1). Hypertension, hyperlipidemia, Kawasaki disease, and heart infection were similar across COI levels (p &gt; 0.05). Levels of physical activity varied significantly across levels of overall COI, with the highest levels reported in the lowest COI group (50.4% with &gt; 10 hours PA/week) (Chi-Squared; p = 0.007). Positive screening rates varied significantly by level of COI (p = 0.013) (Figure 2). The overall level of education, health environment, and socioeconomic COI did not predict positive screening outcomes in logistic regression analysis (all p&gt;0.05). Conclusion: Prevalence of cardiac risk factors did not vary significantly across COI levels, however, positive screening rates were highest in moderate and very low COI levels. Simon’s Heart engaged communities across the COI spectrum; however, a majority of children had high or very high COI. Further efforts are needed to expand access to underserved populations of lower COI.