Risultati per: Long COVID: principali risultati, meccanismi e raccomandazioni

Circulation, Volume 150, Issue Suppl_1, Page A4148010-A4148010, November 12, 2024. Background:Severe COVID-19 infection has been associated with acute respiratory distress syndrome (ARDS) and right ventricular (RV) dysfunction. In this study, we report associations between echocardiographic findings and laboratory markers that portend RV failure in patients with ARDS secondary to COVID-19 infection on ECMO.Methods:A single-center study was conducted in the cardiovascular ICU of our institute. A retrospective chart review was performed on 41 patients with COVID-19 on ECMO between March and October 2020. Twenty-two patients had transthoracic echocardiograms (TTE) completed while on ECMO (VV-ECMO = 19, VA-ECMO = 3). Echocardiograms (echo) were obtained pre-cannulation, during ECMO, and post-ECMO decannulation. RV parameters analyzed included tricuspid annular plane systolic excursion (TAPSE), basal diastolic RV diameter, right ventricular fractional area of change (RV FAC), and S’. Laboratory values including BNP, CRP, D-dimer, ferritin, fibrinogen, lactate and troponin were analyzed for correlation with echo findings.Results:TAPSE was significantly lower in deceased patients (1.9± 0.4cm vs 1.3±0.6 cm, P< 0.05). RV FAC and S’ were also lower in the deceased group. TAPSE while on ECMO showed a positive association with peak D-dimer levels in survivors and a negative association in deceased patients. Peri-ECMO fibrinogen and CRP levels were negatively associated with TAPSE in survivors while fibrinogen showed positive association in deceased patients. LDH peak, fibrinogen initial and lactate peak were higher in the deceased[ZQ1] group. There is a trend of increased RV basal diameter in the deceased group (3.9±0.9 vs 4.2±0.9 cm). Last troponin levels were negatively associated with basal diastolic RV diameter while on ECMO in deceased patients.Conclusion:Preservation of RV longitudinal contractility, as reflected by TAPSE, may play an important role in the survival of COVID-19 patients on ECMO. Laboratory markers such as LDH, D-dimer, fibrinogen and lactate may have prognostic value in predicting RV failure. Further studies are required to determine if early initiation of therapies to improve RV systolic function in COVID-19 ECMO patients with ARDS improves outcomes.

Circulation, Volume 150, Issue Suppl_1, Page A4142952-A4142952, November 12, 2024. Background:The significance of left ventricular global longitudinal strain (LV-GLS) for risk stratification of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) without septal reduction therapy remains to be investigated.Aims:To evaluate the prognostic utility of LV-GLS in a long-term follow-up HCM cohort without septal reduction therapy.Methods:We retrospectively enrolled 871 consecutive patients with HCM (mean age 49±13 years, 71% men) who underwent cardiac MRI in our center between January 2010 and December 2013. All study participants never received alcohol septal ablation or surgical myectomy during follow-up. LV-GLS were derived from cine cardiac MRI by using feature tracking method. The primary endpoint was SCD or SCD-equivalent events. The association between LV-GLS and SCD-related endpoints was evaluated by using time-dependent receiver operating characteristic (ROC) analysis, Kaplan-Meier analysis, and multivariable competing risk regression analysis.Results:During median follow-up of 8.8 years, SCD-related endpoint occurred in 45 HCM patients (5.2%). Patients suffering from SCD had higher European Society of Cardiology (ESC) Risk-SCD score (2.2 ± 0.6 vs. 2.6 ± 0.6, P < .001) and absolute LV-GLS (11.4 ± 3.7% vs. 9.3 ± 3.4%, P < .001). According to time-dependent analysis, 9% is an optimal cut-off value for absolute LV-GLS in predicting the primary outcome after a 10-year follow-up. On competing risk regression analysis, absolute LV-GLS ≤ 9% was associated with a higher rate of primary endpoints (subhazard ratio: 2.66 [95% confidence interval: 1.96 to 3.36]) after adjustment for known risk factors. Finally, LV-GLS provided incremental prognostic value over 2020 American College of Cardiology (ACC)/American Heart Association (AHA) risk model (log-likelihood ratios, -262.2 vs -266.2; P = .003) and 2022 ESC risk model (log-likelihood ratios, -268.4 vs -264.9; P = .009), respectively. In the subgroup with Class 3 of recommendation for implantable cardioverter defibrillator, patients with absolute LV-GLS ≤ 9% showed significantly worse prognosis than those with absolute LV-GLS > 9% (p = .002 and .004 for 2020 AHA guideline and 2022 ESC guideline, respectively).Conclusion:Feature tracking LV-GLS derived by cardiac MRI may enable further risk stratification for the subgroup of HCM patients who never accept septal reduction therapy in their lifetime, especially for those recognized as low-risk for SCD based on current guidelines.

Circulation, Volume 150, Issue Suppl_1, Page A4136861-A4136861, November 12, 2024. Background:The voltage-gated potassium ion channel KV11.1 plays a crucial role in cardiac repolarization. Genetic variants in KV11.1 lead to Long QT Syndrome (LQTS), a condition associated with fatal arrhythmias. Approximately 90% of missense variants linked to LQTS cause intracellular protein transport (trafficking) dysfunction. Some KV11.1 channel blockers act as chemical chaperones (e.g., E-4031) and increase KV11.1 channel trafficking. However, these drugs cannot be used in LQTS patients. The underlying mechanisms, such as the protein networks involved in folding and quality control for KV11.1 channel trafficking remain largely unexplored.Methods:We used affinity-purification (e.g., coimmunoprecipitation) coupled with mass spectrometry to quantify protein interaction changes in human embryonic kidney cells expressing wild-type KV11.1 or two trafficking-deficient channel variants in the presence or absence of chemical chaperone E-4031. After co-immunoprecipitations and protein digestions, peptides were identified using multiplexed mass spectrometry.Results:We identified 572 protein interactions enriched in KV11.1-expressing cells. We used bioinformatic analysis to make a cellular model showcasing likely KV11.1 protein interactions localization from early biogenesis and transcription to plasma membrane expression (Figure 1). We revealed proteins responsible for protein folding, translation, proteasomal degradation, and others with most protein interactions significantly elevated in the genetic variants compared to wild-type (Figure 2). Upon 24-hour treatment with E-4031, some of these interactions were reduced towards wild-type and indicated potential molecular targets for therapeutic intervention (Figure 3).Conclusions:We report the discovery of novel KV11.1 protein-protein interactions that could be therapeutically targeted to improve KV11.1 trafficking and treat Long QT Syndrome.

Circulation, Volume 150, Issue Suppl_1, Page A4138674-A4138674, November 12, 2024. Introduction:Urocortin-2 (UCN-2), a peptide which is part of the corticotropin-releasing factor (CRF) family, functions as an autocrine and paracrine factor, exerting its effects on cardiac and pulmonary function through agonism of CRF2 receptors. Although acute administration of UCN-2 has shown promise by improving heart and lung function in conditions like heart failure (HF) and pulmonary hypertension (PH), its limited stability impedes its chronic therapeutic use.Hypothesis:In this study, we explored the efficacy of COR-1389, a potent, selective and long-acting CRF2 agonist peptide, in the Sugen 5416 (VEGFR2 inhibitor, Su) combined with hypoxia (Hx) rat model of PH and right heart failure (RHF).Methods:To this aim, male adult Sprague Dawley rats were divided into three groups: Control rats (normoxia) were compared with rats injected subcutaneously with 20 mg/kg Sugen 5416 and exposed to chronic hypoxia for 3 weeks, followed by 2 weeks of normoxia. At 5 weeks, control rats and one SuHx group received subcutaneously vehicle (control and SuHx), while the third group received COR-1389 at a dose of 100 μg/kg every 4 days subcutaneously for 3 weeks (SuHx + COR-1389). At 8 weeks, cardiac and pulmonary hemodynamic functions of the three groups were evaluated using echocardiography and right heart catheterization, and heart and lung tissue were evaluated by histology and immunohistochemistry.Results:Compared to controls (n=10), SuHx exhibited increased mean pulmonary arterial pressure (mPAP), right ventricle (RV) hypertrophy (Fulton Index/body weight), muscularization of distal pulmonary arteries, RV fibrosis and cardiomyocyte hypertrophy, alongside reduced RV systolic function (Tricuspid Annular Plane Systolic Excursion, TAPSE) and cardiac output (CO). Conversely, compared to the SuHx + vehicle group (n=11), curative treatment with COR-1389 for 3 weeks in SuHx rats (n=13) led to enhanced RV systolic function (TAPSE) and CO, together with reductions in mPAP, RV hypertrophy, muscularization of pulmonary arteries, RV fibrosis and cardiomyocyte hypertrophy. Systolic blood pressure remained unchanged across all groups.Conclusion:These findings indicate that COR-1389 ameliorates the deteriorating cardiopulmonary parameters observed in the SuHx model and represents a promising approach for the treatment of PH and RHF.

Circulation, Volume 150, Issue Suppl_1, Page A4143985-A4143985, November 12, 2024. Introduction:Endothelial dysfunction can trigger the development and progression of cardiovascular disease. We hypothesize that cardiovascular PASC is induced by persistent endothelial dysfunction mediated via asymmetric-dimethylarginine (ADMA, the endogenous inhibitor of endothelial nitric oxide synthase). ADMA levels rise in response to viral infections, but it is usually degraded by the enzyme DDAH1, which is inhibited by chronic inflammation and oxidative stress. This study aims to determine whether cardiovascular PASC is associated with endothelial dysfunction and to clarify the role of ADMA in this relationship.Methods:We recruited subjects who had been previously infected and developed cardiovascular symptoms (PASC+), those who had been infected but did not have PASC (PASC-), and those who had never been infected (controls) (n=20 each). Groups were matched for age, sex, and BMI and underwent blood draws and fat biopsies. Vascular function was assessedin-vivovia ultrasound imaging andex-vivoin fat-isolated arterioles.Results:Compared to PASC- and controls, PASC+ subjects exhibited 80% higher serum levels of ADMA and 40% reduced nitric oxide levels. DDAH1 activity was elevated in the PASC+, suggesting a compensatory mechanism for the elevated ADMA levels. However, PASC+ obese subjects exhibited substantially lower DDAH1 activity than non-obese subjects, which was associated with lower insulin sensitivity and higher ADMA levels. Compared to the other two groups, the PASC+ group exhibited lower brachial artery vasoreactivity, while nitroglycerin-induced dilation did not differ statistically, suggesting impaired endothelial function. In the PASC+ group, microvascular recruitment in response to reactive hyperemia was diminished, as was the ex vivo measured flow-induced arteriolar dilation and NO generation. Left ventricle (LV) dysfunction was observed in 80% of the PASC+ group, as opposed to 5% of the PASC- and controls. The LV ejection fraction and global longitudinal strain (GLS) were substantially reduced in the PASC+ group, which was correlated with higher ADMA, C-reactive protein, and troponin-1, as well as lower NO and vascular function. Obese PASC+ subjects had the highest ADMA and the lowest endothelial-dependent vasodilation and insulin sensitivity.Conclusion:Cardiovascular PASC symptoms are related to persistent endothelial dysfunction and elevated ADMA levels, which may be further exacerbated by obesity and reduced DDAH1 activity.

Circulation, Volume 150, Issue Suppl_1, Page A4148117-A4148117, November 12, 2024. Background:Tricuspid regurgitation (TR) is a prevalent disease in the population and is usually progressive. Most patients are treated with conservative management due to the risk involving transcatheter tricuspid valve replacement (TTVR) and surgical tricuspid valve replacement (STVR). The TRI-SCORE was developed to evaluate the severity of patients with TR and their risk of undergoing a correction procedure. However, there is still controversy regarding the cutoff value of the score. Therefore, we aim to perform a systematic review and meta-analysis comparing the cutoffs ≥6 with =6 with

Circulation, Volume 150, Issue Suppl_1, Page A4141333-A4141333, November 12, 2024. Background:COVID-19 is a multiorgan disease characterized by a prothrombotic state and increased risk of venous thromboembolism (VTE), especially in hospitalized patients. Although prior studies have attempted to identify predictors of VTE, restricted sample size and use of administrative claims data have limited such analyses. We conducted a multivariable analysis to identify predictors of VTE in hospitalized patients with COVID-19 in a multicenter patient-level registry.Methods:We utilized data from the CORONA-VTE Network, a US multicenter registry of 10,420 adult (≥18 years) patients with PCR-confirmed COVID-19 of whom 3,844 were hospitalized. The primary outcome was time-to-first-event for a composite of adjudicated pulmonary embolism and deep vein thrombosis (e.g. lower extremity, mesenteric, gonadal vein, etc.) during 90-day follow-up. The candidate variables were selected by a priori clinical consensus. The variables with ≥20% missing data were excluded, whereas those with missing data

Circulation, Volume 150, Issue Suppl_1, Page A4140903-A4140903, November 12, 2024. Background:Patients with multivessel coronary spasm showed relatively poor outcomes in vasospastic angina. Recent report also revealed that Ergovonine response definite group showed poor clinical outcomes compared to the Ergovonine response intermediate group. The purpose of this study is to evaluate the clinical impact of Ergovonine provocation definite or intermediate response in multivessel vasospastic angina patients.Methods:A total of 428 patients between May 2010 to November 2013, diagnosed as multivessel vasospastic angina who were registered in the Vasospastic Angina Korea (VA-KOREA) were enrolled. Patients were divided into Ergovonine provocation response definite group (n=111) and intermediate group (n=317). The primary endpoint was cumulative incidece of cardiac death, new onset arrhythmia, acute coronary syndrome, re-admission due to chest pain during 3 years follow-up.Results:In the baseline clinical chracteristics, Ergovonine response definite group had less proportion of male patients (32.4% vs. 49.8%, p=0.002). Other conventional cardiovascular risk factors were similar between two groups. In the angiographic characteristics, electrocardiogram changes during Ergovonine provocation was higher in the deinite group including ST change (18% vs 10.7%; p=0.046), ST elevation (16.2% vs 2.8%; p

Circulation, Volume 150, Issue Suppl_1, Page A4123814-A4123814, November 12, 2024. Background:Obesity shortens life expectancy, while bariatric surgery causes large weight loss and increases median life expectancy by approximately 3 years. However, weight regain after bariatric surgery is common, and its impact on health remains uncertain. In this study, we examined whether weight regain following bariatric surgery is associated with long-term cardiovascular outcomes and mortality.Methods:We analyzed patients undergoing bariatric surgery in the prospective Swedish Obese Subjects study, aged 37-60 with a BMI≥34 (men) or ≥38 (women), recruited 1987-2001. Patients who regained ≥20% of their 1-year weight loss after 4 years (regain group; n=715) were compared to those who regained less (maintenance group; n=631). Information on cardiovascular disease as well as overall and cardiovascular mortality was obtained from the Swedish Population and Address Register, the Swedish Cause of Death Register, and the Swedish National Patient Register. Median follow-up was 27 years.Results:Average weight change from year 1 to year 4 was +12.8 kg and -0.2 kg in the regain and maintenance groups, respectively. The incidence of major adverse cardiovascular events (myocardial infarction, stroke and heart failure) was similar between the groups, with 185 events in the regain group and 137 in the maintenance group. This corresponds to 11.6 events per 1000 person-years (95% CI: 10.1-13.5) for the regain group, and 10.0 events per 1000 person-years (95% CI: 8.3-12.4) for the maintenance group. The adjusted HR was 1.16 (95% CI: 0.92-1.46), p=0.213.During follow-up, there were 216 deaths in the regain group and 184 in the maintenance group, resulting in nearly identical overall mortality rates of 12.4 per 1000 person-years for both groups (95% CI for regain: 10.9-14.2, maintenance: 10.9-14.3). The number of deaths from cardiovascular disease was 77 in the regain group and 57 in the maintenance group, corresponding to similar incidence rates of 4.4 per 1000 person-years (95% CI: 3.5-5.5) and 3.8 per 1000 person-years (95% CI: 3.0-5.0), respectively (p=0.550).Conclusions:The incidence of major adverse cardiovascular events, as well as total and cardiovascular mortality, was similar between the weight regain and maintenance groups. This suggests that the beneficial association between bariatric surgery and reduced cardiovascular events persists despite weight regain.

Circulation, Volume 150, Issue Suppl_1, Page A4143317-A4143317, November 12, 2024. Background:Recent observations suggest that residual left atrial (LA) dyssynchrony after cardiac resynchronization therapy (CRT) may have prognostic significance. Since LA dyssynchrony implies prolongation of the LA reservoir phase, measuring the duration of the LA reservoir phase should offer similar prognostic information.Purpose:To investigate the impact of LA reservoir phase duration on long-term survival after CRT.Methods:In a recent prospective multicenter study of 168 patients, LA strain was measured by speckle-tracking echocardiography before and 7±1 months after CRT. LA reservoir strain was measured as the difference between peak and minimum global strain during the atrial cycle and LA reservoir phase duration as the time from onset shortening in the left ventricle to peak LA reservoir strain. Since LA reservoir strain 516 ms) (lower panel in the Figure). Patients with preserved LA reservoir strain but prolonged LA reservoir phase duration had similar outcome as patients with reduced LA reservoir strain (HR 1.10, 95% CI: 0.49–2.51).Conclusions:LA reservoir strain ≥18% combined with reservoir phase duration ≤516 ms is associated with excellent long-term survival after CRT. Prolonged reservoir phase duration is linked to adverse long-term outcomes in patients with preserved LA reservoir strain. Therefore, reservoir phase duration provides added value for risk prediction after CRT that may be clinically important.

Circulation, Volume 150, Issue Suppl_1, Page A4144767-A4144767, November 12, 2024. Background:The efficacy of beta-blockers (BB) in patients with heart failure and reduced ejection fraction (EF) is well established. In fact, current guidelines widely recommend BB use after myocardial infarction (MI). However, the effects of long-term BB therapy in patients with acute myocardial infarction (AMI) and preserved EF remains uncertain.Hypothesis:The use of BB after AMI improves long-term outcomes in patients with preserved EF.Aims:To compare the long-term effects of BB with non-BB post AMI in patients with preserved EF.Methods:PubMed, Embase, and Cochrane Library were systematically searched from inception to May 2024 to identify studies comparing BB with no BB use after AMI in patients with preserved EF ( >50%), with a minimum follow-up of 1 year. We pooled hazard ratios (HR) with 95% confidence intervals (CI) to preserve time-to-event data in the pooled analysis. Statistical analyses were performed using R software version 4.3.1.Results:We included two randomized controlled trials and eight cohorts comprising 25,357 patients, of whom 47% received BB and 52% were men. Mean age of patients ranged from 58 to 66.2 years. Follow-up ranged from 1 to 5.2 years. There were no significant differences between groups in all-cause mortality (HR 0.86; 95% CI 0.68-1.08; p=0.20; Figure 1A), myocardial infarction (HR 1.02; 95% CI 0.84-1.24; p=0.86; Figure 1B), or hospitalization for heart failure (HR 1.06; 95% CI 0.78-1.43; p=0.71; Figure 1C). However, when performed a leave-one-out sensitivity analysis in all-cause mortality we saw significant results favoring the use of BB after omitting each study.Conclusion:In this meta-analysis, there were no significant differences in all-cause mortality, myocardial infarction, or hospitalization for heart failure when comparing long-term use of BB with no BB use after AMI in patients with preserved EF. Further trials are needed to clarify the role of BB in this setting.

Circulation, Volume 150, Issue Suppl_1, Page A4118444-A4118444, November 12, 2024. Background:Childhood cancer survivors are at risk of right ventricular (RV) dysfunction in relation to cardiac toxicity due to chemotherapy and radiation therapy. This study tested the hypothesis that RV contractile reserve and RV-pulmonary arterial (PA) coupling are altered in long-term survivors of childhood cancers.Methods:Thirty survivors (60% men) aged 24.3 ± 5.2 years at 15.3 ± 6.3 years after completion of chemotherapy and thirty healthy control subjects (47% men) were studied. Resting and submaximal supine bicycle stress echocardiography was performed for assessment of RV fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), left ventricular (LV) and RV longitudinal strain, mitral and tricuspid annular velocities and myocardial acceleration during isovolumic contraction (IVA). The slope of the RV force-frequency relationship was derived from the change in IVA with the change in heart rate during exercise (△IVA/△heart rate), while RV-PA coupling was determined by the ratio between TAPSE and pulmonary arterial acceleration time indexed to RV ejection time (PAATi).Results:At rest, tricuspid annular systolic velocity and RV systolic strain were significantly lower in survivors (P< 0.05 for both), while RV FAC, TAPSE and IVA were similar between the two groups (P > 0.05 for all). During submaximal exercise testing, all RV systolic functional indices were significantly lower in survivors than controls (P< 0.05 for all). The slope of the RV force-frequency relationship was significantly flatter in survivors compared to controls (0.038 ± 0.002 vs 0.059 ± 0.003 m/sec2beats/min,P< 0.001). For RV-PA coupling, TAPSE/PAATi was similar between survivors and controls at baseline but became significantly lower in survivors during submaximal exercise (P= 0.002).Conclusions:The RV contractile reserve and RV-PA coupling are impaired during exercise in long-term survivors of childhood cancers. Future studies aimed at determining the clinical and prognostic significance of these impairments are warranted.

Circulation, Volume 150, Issue Suppl_1, Page A4137534-A4137534, November 12, 2024. 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 theMyocarditisAfterCOVIDVaccination (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 >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 > 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.

Circulation, Volume 150, Issue Suppl_1, Page A4145278-A4145278, November 12, 2024. Background:Metabolic syndrome (MetS), a cluster of risk factors, has been linked to higher risk of dementia in older adults. However, the composite impact of long-term variability of metabolic parameters from childhood on midlife cognitive function is unclear.Methods:We studied 1145 midlife participants of the Bogalusa Heart Study (age at enrollment: 12.2 ± 5.4 years, follow-up: 36.1 ± 3.4 years, age at last exam (midlife): 48.3 ± 5.0 years, 60.9% women, 33.7% Black participants) with ≥3 measurements of metabolic parameters (systolic blood pressure (SBP), fasting blood glucose (FBG), triglyceride (TG), high density lipoprotein (HDL), and body mass index (BMI)) across follow-up. MetS was defined by the National Cholesterol Education Program guidelines, but using BMI >30 kg/m2for abdominal obesity. Long-term variability of SBP, FBG, TG, HDL, and BMI from childhood were measured as the residual standard deviation (RSD). Repeated measurements of each parameter were fitted in random-effect models to obtain individual growth curves. Using the growth curves, RSD was obtained as the SD of the difference between each observed and predicted parameter level. A composite variability score (range, 0-10) was defined by 1) assigning 0 points to the lowest tertile of RSD and 2 points to the highest tertile for each parameter, then 2) summing the points for all 5 parameters. Midlife cognitive function was measured by 8 neuropsychological (NP) tests. NP test results were categorized into 3 distinct NP profiles (optimal, average, mixed-low) using cluster analysis. Associations between the composite variability score and NP profiles were analyzed using multinomial logistic regression models, adjusting for education status. Sensitivity analysis excluding participants with MetS at midlife were also performed.Results:A total of 348 (30.4%) participants had MetS at midlife. The odds of having mixed-low cognitive function at midlife increased by 13.3% (OR 1.13, 95% CI 1.03, 1.24) for a 1-unit increase in the composite variability score, compared to optimal cognitive function, adjusted for education status. Sensitivity analysis showed consistent results in participants without MetS at midlife (OR 1.18, 95% CI 1.05, 1.33).Conclusions:A graded association was observed between composite long-term variability in metabolic parameters from childhood and poorer midlife cognitive function. Lowering variability of metabolic parameters may be beneficial to midlife cognitive function.

Circulation, Volume 150, Issue Suppl_1, Page A4117883-A4117883, November 12, 2024. Introduction/Background:Cardiovascular symptoms appear in a high proportion of patients in the few months following a severe SARS-CoV-2 infection. Non-invasive methods to predict disease severity could help personalizing healthcare and reducing the occurrence of these symptoms.Research Questions/Hypothesis:We hypothesized that blood long noncoding RNAs (lncRNAs) and machine learning (ML) could help predict COVID-19 severity.Goals/Aims:To develop a model based on lncRNAs and ML for predicting COVID-19 severity.Methods/Approach:Expression data of 2906 lncRNAs were obtained by targeted sequencing in plasma samples collected at baseline from four independent cohorts, totaling 564 COVID-19 patients. Patients were aged 18+ and were recruited from 2020 to 2023 in the PrediCOVID cohort (n=162; Luxembourg), the COVID19_OMICS-COVIRNA cohort (n=100, Italy), the TOCOVID cohort (n=233, Spain), and the MiRCOVID cohort (n=69, Germany). The study complied with the Declaration of Helsinki. Cohorts were approved by ethics committees and patients signed an informed consent.Results/Data:After data curation and pre-processing, 463 complete datasets were included in further analysis, representing 101 severe patients (in-hospital death or ICU admission) and 362 stable patients (no hospital admission or hospital admission but not ICU). Feature selection with Boruta, a random forest-based method, identified age and five lncRNAs (LINC01088-201, FGDP-AS1, LINC01088-209, AKAP13, and a novel lncRNA) associated with disease severity, which were used to build predictive models using six ML algorithms. A naïve Bayes model based on age and five lncRNAs predicted disease severity with an AUC of 0.875 [0.868-0.881] and an accuracy of 0.783 [0.775-0.791].Conclusion:We developed a ML model including age and five lncRNAs predicting COVID-19 severity. This model could help improve patients’ management and cardiovascular outcomes.

Circulation, Volume 150, Issue Suppl_1, Page A4145167-A4145167, November 12, 2024. Background:Cardiogenic shock (CS) and cardiac arrest (CA) are serious complications in ST-elevation myocardial infarction (STEMI) patients, with lack of long-term data according to their timing of occurrence.Objective:This study sought to determine the incidence and the relationship between timing of occurrence and prognostic impact of CS and CA following STEMI in the long-term follow-up.Methods:We conducted a retrospective analysis of consecutive STEMI patients treated from 2004 to 2017. Patients were divided into four groups based on the occurrence of neither CA nor CS, CA only, CS only, and both CA and CS (CA-CS-, CA+, CS+ and CA+CS+, respectively). Adjusted Cox regression analysis was used to assess the independent association between the CS and CA categories and mortality. The timing of their occurrence was evaluated according to initial cardiac catheterization as pre-, during- or post-procedure.Results:A total of 1,603 STEMI patients were followed for a median of 3.6 years. CA and CS occurred in the 12.2% and 15.9% of patients, and both impacted long-term mortality [adjusted HR 2.59 (95%CI 1.53-4.41), p