Abstract 4140983: LVEF by echocardiogram does not correlate with findings on advanced cardiac imaging in cardiac sarcoidosis patients

Circulation, Volume 150, Issue Suppl_1, Page A4140983-A4140983, November 12, 2024. Background:Sarcoidosis is a systemic non-caseating granulomatous disease that can involve numerous organs, classically lung and lymph node. Patients with cardiac involvement typically have poorer outcomes, with left ventricular ejection fraction (LVEF) predicting mortality. There is little contemporary data evaluating the relationship of baseline LVEF at time of active cardiac sarcoidosis (CS) involvement or change in LVEF over time in patients with abnormal cardiac positron emission tomography (CPET) or cardiac magnetic resonance (CMR).Hypothesis:Abnormal CPET or CMR findings suggestive of CS will be associated with concurrently lower LVEF, as well as progressive decline in LVEF over long-term follow-up in those with CS.Methods:At a major sarcoidosis referral center, a retrospective analysis was performed on 1,901 biopsy-proven sarcoidosis patients and 358 probable CS patients by 2014 HRS Expert Consensus on Diagnosis. All echocardiograms, CPET, and CMR data were compiled. LVEF at time of positive and negative CMR and CPET within 6 months of each other, as well as LVEF change on long-term follow-up were analyzed by t-test and Tukey’s Studentized Range Test.Results:CPET and CMR positive findings did not correlate with lower LVEF at time of abnormal findings. Over an average of 4.98 years (range 0.25 to 11.68 years), LVEF by echocardiogram did not significantly change in patients with positive, negative, or discordant CPET/CMR imaging.Conclusions:Structural abnormalities by echocardiogram do not correlate with positive or negative CPET/CMR and are of little utility in early detection of cardiac sarcoidosis. These data suggest that combined CPET/CMR protocols increase the sensitivity of identifying early cardiac involvement of sarcoidosis. A normal echocardiogram should not be reassuring to the clinician against possible cardiac involvement of sarcoidosis.

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Novembre 2024

Abstract 4137782: Fibrinogen-to-Albumin Ratio Does Not Correlate with Comprehensively Assessed Coronary Artery Disease Severity or High-Risk Plaque Features on Coronary Computed Tomographic Angiography

Circulation, Volume 150, Issue Suppl_1, Page A4137782-A4137782, November 12, 2024. Background:Fibrinogen-to-albumin ratio (FAR) has been proposed as a readily available inflammatory biomarker associated with coronary artery disease (CAD). However, its association with CAD severity and prognosis has predominantly been assessed in patients with acute coronary syndromes (ACS). The Leiden score is a validated comprehensive measure of CAD incorporating stenosis proximity, severity, and plaque type that independently predicts cardiovascular events. Whether FAR is associated with Leiden score or high-risk plaque features on coronary computed tomographic angiography (CCTA) in stable outpatients is unknown.Methods:Adult outpatients undergoing clinically indicated CCTA were enrolled (5/2021-9/2023) in a prospective study assessing the relationship of plaque to immune markers and provided same-day pre-scan peripheral venous blood samples. CCTAs were post-processed and analyzed by the consensus of two expert readers blinded to clinical data using a 17-segment model to determine coronary artery calcium (CAC), Leiden score, and high-risk plaque features. Patients were grouped by FAR (quartiles), Leiden score (20), and CAC score (0, >0-100, >100-300, >300-1000, >1000). Numerical variables were compared via Wilcoxon and Kruskal-Willis tests. Spearman correlation was calculated between FAR and Leiden score.Results:Of 284 patients, 53.8% were male, 86.7% were white, and 58.8% were on a statin (Table 1). Median FAR was 70.3 mg/g, 64.0% had a non-zero CAC score, and 25.0% had at least one segment with one high-risk plaque feature. Across quartiles of FAR, there was no difference in Leiden score (5.8 (IQR: 0.0-18.5), 12.4 (3.1-20.7), 8.0 (0.0-19.9), 6.8 (0.0-21.1), p=0.50) or probability of having at least one segment with at least one (29.6%, 23.9%, 23.9%, 22.5%, p=0.69) or two (18.3%, 14.1%, 12.7%, 15.5%, p=0.66) high-risk plaque features. There was no correlation between FAR and Leiden score (R=0.03, p=0.66). There was no difference in FAR when stratified by Leiden score (Table 1, p=0.53), CAC score (Table 2, p=0.50), or number of segments with at least one high-risk plaque feature (Table 3, p=0.18).Conclusion:In a prospective cohort of adult outpatients across a wide spectrum of CAD burden with high rates of baseline statin use, FAR was not associated with CAD or presence of high-risk plaque features on CCTA. Further evaluation of its role as an inflammatory biomarker in larger populations, particularly patients without ACS, is required.

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Novembre 2024

Abstract 4141276: Valvular oxidized phospholipids correlate with severity of human aortic valvular stenosis

Circulation, Volume 150, Issue Suppl_1, Page A4141276-A4141276, November 12, 2024. Introduction:Aortic valve stenosis (AVS) is a degenerative disease characterized by progressive calcification and stenosis, driven by a multifactorial inflammatory process. Oxidized phospholipids (OxPL) have been implicated in this process, yet their presence in aortic valve tissue remains unexplored. This study aims to fill this gap by developing a sensitive method to identify and quantify OxPL in the plasma and tissue of patients with severe AVS.Methods:We obtained aortic valve tissue from 70 patients undergoing aortic valve replacement surgery. The tissue samples were subjected to derivatization with DNPH, followed by LC/MS/MS analysis, enabling the identification and quantification of 60 individual OxPL across five different phospholipid classes.Results:Our analysis identified 34 OxPL species across five phospholipid classes in human valvular tissue, including oxidized phosphatidylcholine (OxPC), phosphatidylethanolamine (OxPE), phosphatidylinositol (OxPI), and phosphatidylserine (OxPS). OxPC was the most abundant class, with PONPC being the most prevalent molecule, constituting 35% of total OxPL. We observed a significant increase (p

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Novembre 2024

Safety and efficacy of individual target transcranial magnetic stimulation to stimulate the most negative correlate of DLPFC-pgACC in the treatment of major depressive disorder: study protocol of a double-blind, randomised controlled trial

Introduction
Major depressive disorder (MDD) is a common mental disorder that is characterised by high morbidity, high rates of relapse, high rates of disability and, in severe cases, suicide ideas or even behaviour causing significant distress and burden. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique widely used in the clinical treatment of MDD. Nevertheless, due to the imprecise selection and positioning of stimulation targets, their response rate is not as satisfactory. This trial was designed to treat MDD based on functional connectivity with individual target-TMS (IT-TMS) to stimulate the dorsolateral prefrontal cortex (DLPFC) where it correlates most negatively with the pregenual anterior cingulate cortex (pgACC). We will validate the safety and efficacy of IT-TMS for MDD using pgACC as an effector target, analyse the underlying antidepressant mechanism of the DLPFC-ACC brain network and search for neuroimaging markers that predict the efficacy of TMS.

Methods and analysis
This is a single-centre, randomised, double-blind and sham-stimulation-controlled clinical trial. We aim to recruit approximately 68 depressed patients with MDD aged 18–60 years. Eligible participants will be randomised into the DLPFC-pgACC localisation and sham stimulation groups. The IT-TMS treatment will last 10 days and will be combined with antidepressant medication. Assessments will be confirmed at baseline, on day 5 of treatment and at the end of treatment with follow-up at weeks 2, 4 and 8 after the end of treatment. The primary outcome measure is the difference in the Hamilton Depression Scale score between baseline and end of treatment.

Ethics and dissemination
The Ethics Committee of the First Affiliated Hospital of the Air Force Medical University has approved this clinical trial (project code: XJLL-KY20222111). The trial’s results will be published in international peer-reviewed journals and presented at academic conferences.

Trial registration number
ClinicalTrials.gov PRS (ID: NCT05577481).

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Novembre 2024