Marker Of Cardiac Dysfunction Research Articles

Feto-maternal indicators of cardiac dysfunction as a justification for the cardiac origins for pre-eclampsia.

While the pathophysiology of pre-eclampsia has been postulated as being secondary to placental dysfunction, a cardiac origin has more recently been proposed. Although an association between fetal congenital cardiovascular disease and pre-eclampsia has been demonstrated, no precise pathophysiologic mechanism for this association has been described. This review highlights the current biophysical (including echocardiography and Doppler indices) and biochemical (including proteomic, metabolomic and genetic/transcriptomic) markers of cardiac dysfunction that have been investigated in maternal and fetal cardiac disease and their overlap with predictors of pre-eclampsia. Common pathways of inflammatory and anti-angiogenesis imbalance, endothelial damage, and oxidative stress have been demonstrated in both cardiovascular disease and pre-eclampsia and further investigation into these pathways could help to elucidate the common pathophysiologic mechanisms linking these disorders.

Correlation of blood-based immune molecules with cardiac gene expression profiles reveals insights into Chagas cardiomyopathy pathogenesis.

Understanding compartmentalized immune responses in target organs is crucial for elucidating the pathogenesis of various diseases. However, obtaining samples from affected vital organs often poses safety challenges. In this study, we aimed to investigate potential correlations between the levels of disease-associated immune molecules in the bloodstream with their gene expression profiles in the hearts of patients suffering from Chagas Cardiomyopathy (CCC). This debilitating and often fatal condition is caused by infection with the protozoan Trypanosoma cruzi. Blood samples were analyzed using the Bio-Plex platform. Gene Expression Omnibus (GEO) database was used to determine gene expression profile in heart tissue from CCC and non-Chagas controls (CTRL). Elevated levels of inflammatory cytokines were detected in the plasma of CCC patients, and these levels correlated with clinical indicators of deteriorating cardiac function. Notably, 75% of the soluble factors assessed in the plasma exhibited a consistent relationship with their gene expression levels in the cardiac tissue of CCC patients. Analysis of interactions and signaling pathways related to these molecules revealed an overrepresentation of inflammatory pathways in both blood and heart compartments. Moreover, we identified that differentially expressed genes in CCC cardiac tissue were primarily associated with T-cell signaling pathways and correlated with the presence of CD8+ T cells in the myocardium. Our findings establish a strong correlation between relevant immune molecules and their signaling pathways in both the blood and heart tissue in CCC. This validates the use of blood as a non-invasive medium for understanding immunopathology and identifying markers for cardiac dysfunction in Chagas disease.

Grapevine Shoot Extract Rich in Trans-Resveratrol and Trans-ε-Viniferin: Evaluation of Their Potential Use for Cardiac Health.

A grapevine shoot extract (GSE) was obtained using ultrasound-assisted extraction and characterized. The main phenolic constituents were identified as stilbenoids. Among them, trans-resveratrol and trans-ε-viniferin stood out. The GSE was administered to an isoproterenol-induced myocardial injury animal model. The extract alleviated the associated symptoms of the administration of the drug, i.e., the plasma lipid profile was improved, while the disturbed plasma ion concentration, the cardiac dysfunction markers, the DNA laddering, and the necrosis of myocardial tissue were diminished. This effect could be related to the anti-oxidative potential of GSE associated with its antioxidant properties, the increased levels of endogenous antioxidants (glutathione and enzymatic antioxidants), and the diminished lipid peroxidative markers in the heart. The results also revealed angiotensin-converting enzyme (ACE)-inhibitory activity, which indicated the potential of GSE to deal with cardiovascular disease events. This work suggests that not only trans-resveratrol has a protective role in heart function but also GSE containing this biomolecule and derivatives. Therefore, GSE has the potential to be utilized in the creation of innovative functional ingredients.

Reduced left ventricular elastance as a novel marker of cardiac dysfunction in patients with severe liver disease

Abstract Introduction Left ventricular (LV) elastance reflects the contractility of the myocardium and is an index of cardiac performance. Liver cirrhosis is characterized by reduced systemic vascular resistance, leading to reduced afterload on the LV. This, combined with increased blood volume, results in increased preload, increased stroke volume and remodeling of the LV. The latter may result to alterations in end-systolic LV elastance (Ees) a parameter that has not been extensively studied in cirrhotics. Purpose To investigate the relationship between Ees and the severity of liver cirrhosis. Methods We conducted a cross-sectional study in which transthoracic echocardiography was performed in 75 patients with liver cirrhosis (mean age 58.9±8.5 years, 74.7% males). A verified noninvasive single-beat formula was used to calculate Ees. Specifically, Ees was calculated employing systolic and diastolic blood pressures, echo-derived stroke volume (SV), ejection fraction (LVEF) and the estimated normalized ventricular elastance at arterial end-diastole (ENd). The ENd was estimated from a group-averaged value adjusted for individual contractile/loading effects. The Model for End-Stage Liver Disease-Sodium (MELDNa) score, a widely used tool for assessing liver disease severity was also calculated. We compared Ees between patients with MELDNa scores above and below 15, which is the cutoff commonly used to indicate severe liver disease. Results Mean Ees in the cohort of the 75 patients was 2.34±0.81mmHg/ml. Ees was correlated with end-systolic LV volume (rho=-0.448, p<0.001), SV (rho=-0.568, p<0.001) and systolic blood pressure (rho=0.283, p=0.014), but not with LVEF. Mean MELDNa score was 15.5±7.3 and 32 (42.7%) of patients had MELDNa score ≥ 15. Mean Ees in patients with MELDNa score above 15 was significantly lower than in patients with MELDNa score below 15 (2.08±0.61mmHg/ml vs 2.54±0.89mmHg/ml, p=0.015). The association remained significant in a multivariate model after adjusting for age, sex, and body surface area (B=-0.426, p=0.015). Conclusion Our study demonstrates that patients with severe liver disease have lower Ees, indicating impaired LV function. Ees could be a useful marker for identifying patients with liver cirrhosis who are at increased risk of cardiovascular complications. Further research is needed to better understand the mechanisms underlying this association and to propose therapeutic interventions aimed at improving LV function in this special population.

Association of GDF15, NTpoBNP and PLGF with subclinical cardiac dysfunction in type 2 diabetes: effects of novel antidiabetic treatment

Abstract Background In type 2 diabetics, we investigated the effects of insulin, GLP-1Ra, SGLT-2i and their combination on blood biomarkers of cardiac function and their association with left ventricular and atrial function. Patients and methods A total of 200 diabetics (60.3±10.3-year-old) treated with metformin were randomized to insulin (n= 50), liraglutide (n=50), empagliflozin (n=50) or their combination (GLP-1RA+SGLT-2i) (n= 50) . We measured at baseline and 6 months post-treatment: (a) perfused boundary region of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness), (b) pulse wave velocity (PWV), (c) Left Ventricular (LV) Global Longitudinal Strain (GLS) and Torsion, (d) LV Global Work Index (GWI), Global Constructive Work (GCW), Global Wasted Work (GWW), Global Work Efficiency (GWE), (e) Left atrial reservoir strain (LASr) and (f) Growth/Differentiation Factor-15 (GDF-15), NTproBNP, Placental Growth Factor (PLGF) as markers of cardiac dysfunction. Results Increasing GGDF-15 levels at baseline were related with increasing PWV (r=0.357, p<0.001). Moreover, increasing GDF-15 was related with reduced absolute GLS values (r=-0.425, p=0.005), increased LV Torsion (r=0.309, p=0.035), Twisting Velocity (r=0.345, p=0.018) and E/E’ (r=0.307, p=0.041) as well as reduced Untwisting velocity (r=-0.383, p=0.008) and LASr (r=-0,388, p=0.005). Increasing NTproBNP concentration at baseline was related with increasing PWV (r=0.445, p=0.001 and PBR5-25 (r=0.222, p=0.04) . Also, increasing NTroBNP was related with reduced absolute GLS (r=-0.454, p=0.002), LV GL strain rate (r=-0.360, p=0.008) , increased LV Torsion (r=0.329, p=0.029) and E/E’ (r=0.365, p=0.021). Increasing NTproBNP was also related with decreasing GWI (r=-0.471, p<0.001), GWE (r=-0.555, p<0.001), Untwisting velocity (r=-0.383, p=0.008) and LASr (r=-0,424, p=0.002). PLGF concentration at baseline was related with reduced absolute GLS (r=-0.341, p=0.012), LV GL strain rate (r=-0.302, p=0.008) and LASr (r=-0.321, p=0.036). At 6 months, the reduction of GDF-15 and NTproBNP levels was related with the respective reduction of PWV (p=0.022 and p=0.34) Furthermore, the reduction of NTproBNP at 6 months was related with an increase of GWI and GWE (r=0.455, p=0.006/ r=0.631, p=0.001,respectively). In patients treated with GLP-1RA, SGLT-2i and their combination, there was greater improvement of GLS, Torsion, Myocardial Work, LASr, NTproBNP, GDF-15 PLGF compared to patients treated with insulin (p<0.05) post-treatment. In patients treated with insulin, NTproBNP, GDF-15 and PLGF changes post-treatment were not related with the respective changes of the examined cardiac and vascular markers. Conclusion Elevated levels of GDF15, PLGF and NTproBNP are associated with cardiac and vascular dysfunction in patients with type 2 diabetics and their improvement after 6 months of treatment with GLP-1RA and /or SGLT2i is associated with improved cardiovascular function.

Markers of cardiac dysfunction associated with inflammation in a cohort of patients with acute decompensation of cirrhosis.

Inflammation underpinning acute decompensation (AD) of liver disease is an important driver for the development of acute-on-chronic liver failure or death. We aimed to investigate associations between inflammatory biomarkers and impaired cardiac function in patients admitted for AD of cirrhosis. This is a retrospective analysis of a well-characterized prospective cohort of patients with AD of liver disease admitted to a tertiary referral center. All patients had echocardiographic assessment of cardiac function and serum samples at admission. We reclassified patients according to the CLIF-C AD score, measured inflammatory (IL-6, IL-8, TNF-ɑ, CD206) and cardiac-specific (NT-proBNP, troponin T) biomarkers and tested for associations with echocardiographic parameters of cardiac function. We explored the impact on outcome of these factors in multivariate analysis. We included 70 patients (58 ± 10 years, 28 women), with a mean CLIF-C AD score of 47 ± 7. Thirty-nine patients (56%) fulfilled the echocardiographic criteria for cardiac dysfunction. We found associations between parameters of diastolic dysfunction and serum concentrations of IL-6 and CD206. Echocardiographic parameters of cardiac function were not associated with markers of liver dysfunction such as the CLIF-C AD score. In multivariate analysis higher MELD, higher NT-proBNP, and IL-8 concentrations as well as the absence of echocardiographic criteria for cardiac dysfunction significantly associated with death during follow-up. We found evidence in favor of a clinically relevant link between serum biomarkers of inflammation (IL-6, CD206) and echocardiographic signals of cardiac dysfunction in patients with acutely decompensated cirrhosis.

Association between epicardial adipose tissue and cardiac dysfunction in subjects with severe obesity.

Epicardial adipose tissue (EAT) plays a role in obesity-related heart failure with preserved ejection fraction. However, the association of EAT thickness with the development of cardiac dysfunction in subjects with severe obesity without known cardiovascular disease is unclear. Determine the association between EAT thickness and cardiac dysfunction and describe the potential value of EAT as an early marker of cardiac dysfunction. Subjects with BMI ≥35 kg/m2 aged 35 to 65 years, who were referred for bariatric surgery, without suspicion of or known cardiac disease, were enrolled. Conventional transthoracic echocardiography and strain analyses were performed. A total of 186 subjects were divided into tertiles based on EAT thickness, of whom 62 were in EAT-1 (EAT <3.8 mm), 63 in EAT-2 (EAT 3.8-5.4 mm), and 61 in EAT-3 (EAT >5.4 mm). Parameters of systolic and diastolic function were comparable between tertiles. Patients in EAT-3 had the lowest global longitudinal strain (GLS) and left atrial contractile strain (LASct). Linear regression showed that a one-unit increase in EAT thickness (mm) was independently associated with a decrease in GLS (%) (β-coefficient - 0.404, p = 0.002), and a decrease in LASct (%) (β-coefficient - 0.544, p = 0.027). Furthermore, EAT-3 independently predicted cardiac dysfunction as defined by a GLS < 18% (OR 2.8, p = 0.013) and LASct<14% (OR 2.5, p = 0.045). Increased EAT thickness in subjects with obesity without known cardiac disease was independently associated with subclinical cardiac dysfunction. Our findings suggest that EAT might play a role in the early stages of cardiac dysfunction in obesity before this may progress to overt clinical disease. This article is protected by copyright. All rights reserved.

Electrocardiographic R wave amplitude in V6 lead as a predictive marker of cardiac dysfunction in Duchenne muscular dystrophy

PurposeDuchenne muscular dystrophy (DMD) is an inherited muscular disease characterized by progressive and fatal muscle weakness. Electrocardiographic (ECG) abnormalities, including abnormal R wave amplitudes are frequently observed in DMD. However, clinical implications of abnormal R wave amplitudes remain unclear. Hence, DMD patients were examined for changes in R wave amplitude over time using synthesized 18-lead ECG and the relationship between R wave amplitude and cardiac function. MethodsThe results of 969 ECG examinations of 193 patients with DMD who underwent electrocardiography and echocardiography on the same day were retrospectively reviewed. ResultsA negative correlation was observed between R wave amplitude and age. Positive correlations between R wave amplitude and left ventricular ejection fraction were observed in leads V4, V5, V6, syn-V7, syn-V8, and syn-V9, with V6 showing the strongest correlation (r = 0.52). Mean R wave amplitude during cardiac dysfunction was lower than that observed with preserved cardiac function in leads V6 to syn-V9. Patients had preserved R wave amplitude up to three years before the onset of cardiac dysfunction, with a sharp decrease two years before cardiac dysfunction in leads V6 to syn-V9. ConclusionsIn DMD patients, the R wave amplitude decreases with age. The sharp decline in R amplitude two years before cardiac dysfunction indicates that electrophysiological damage to the myocardium of the left ventricle lateral to the posterior wall precedes the finding of cardiac dysfunction. The R amplitude in V6 of the standard 12-lead ECG is a convenient predictive marker of cardiac dysfunction, similar to that of the 18-lead ECG.

105 Burning Heart - An Animal Model of Chronic Heart Failure Following Severe Burn Injury

Abstract Introduction Our clinical research unveiled chronic heart failure with preserved ejection fraction (HFpEF) as a long-term sequel in survivors of severe pediatric burn injury due to a yet unknown molecular pathomechanism. Applying a standardized rat model, we systematically determined the pathophysiological impact of burn injury on long-term cardiac performance to uncover systemic and molecular pathomechanisms that may cause post-burn HFpEF development. Methods Male adolescent SD-rats were subjected to a 60 % total body surface area (TBSA) full-thickness burn- or sham-trauma and subsequently characterized after burn-injury by serial transthoracic echocardiography, bulk myocardial next-generation sequencing and proteomics as well as RT-PCR, immuno-blotting (IB), histology and plasma proteomics for cardiac performance and molecular alterations, respectively, at 3, 7, 30 and 90days. Results In comparison to the sham-group (SG), animals from the burn-group (BG) recapitulated typical post-burn clinical traits, such as significant loss in body weight (BG 27 % less than SG at 30d, p&amp;lt; 0.05) or skeletal muscle wasting (27 % less at 30d, p&amp;lt; 0.05) in accord with elevated molecular atrophy markers. We show post-burn cardiac muscle wasting (BG 22 % less at 30d, p&amp;lt; 0.05) and persistent markers of cardiac dysfunction in accord with significant histological cardiomyocyte hypotrophy (BG -8 % at 30d, p&amp;lt; 0.05) and significantly diminished left ventricular (LV) global longitudinal strain and isovolumic relaxation time in BGs, while LV-EF remained unchanged. Weighted gene network correlation analysis from bulk myocardial NGS and clinical traits related activation of immunological and pro-fibrotic pathways in post-burn injury hearts to cardiac dysfunction in BGs. Subsequent RT-PCR and histology confirmed significant myocardial accumulation of cardio-depressive damage associated molecular patterns (i.e., S100A8 and A9) and infiltration by granulocytes and monocytes as well as significant LV fibrosis. Serial plasma proteomic analysis indicated elevated plasma levels of S100A8 and A9 and other heart failure markers that mirrored similar changes in human post-burn plasma samples. Conclusions Here we report the development of HFpEF as a novel systemic consequence of severe burn injury in a rodent model, which warrants further mechanistic and translational studies. Cardiac inflammation and fibrosis are known to negatively impact cardiac performance and may be mechanistic key findings that will guide further therapeutic studies and subsequent validation of post-burn heart failure biomarkers Applicability of Research to Practice This model is part of a translational and interdisciplinary experimental and clinical effort to inform pathophysiology and mechanistics of long-term heart failure in burn patients. Echocardiographic data and parameters from this model are currently being used to evaluate adult survivors of severe burn injury for signs of HFpEF.

Increased biventricular hemodynamic forces in precapillary pulmonary hypertension

Precapillary pulmonary hypertension (PHprecap) is a condition with elevated pulmonary vascular pressure and resistance. Patients have a poor prognosis and understanding the underlying pathophysiological mechanisms is crucial to guide and improve treatment. Ventricular hemodynamic forces (HDF) are a potential early marker of cardiac dysfunction, which may improve evaluation of treatment effect. Therefore, we aimed to investigate if HDF differ in patients with PHprecap compared to healthy controls. Patients with PHprecap (n = 20) and age- and sex-matched healthy controls (n = 12) underwent cardiac magnetic resonance imaging including 4D flow. Biventricular HDF were computed in three spatial directions throughout the cardiac cycle using the Navier–Stokes equations. Biventricular HDF (N) indexed to stroke volume (l) were larger in patients than controls in all three directions. Data is presented as median N/l for patients vs controls. In the RV, systolic HDF diaphragm-outflow tract were 2.1 vs 1.4 (p = 0.003), and septum-free wall 0.64 vs 0.42 (p = 0.007). Diastolic RV HDF apex-base were 1.4 vs 0.87 (p < 0.0001), diaphragm-outflow tract 0.80 vs 0.47 (p = 0.005), and septum-free wall 0.60 vs 0.38 (p = 0.003). In the LV, systolic HDF apex-base were 2.1 vs 1.5 (p = 0.005), and lateral wall-septum 1.5 vs 1.2 (p = 0.02). Diastolic LV HDF apex-base were 1.6 vs 1.2 (p = 0.008), and inferior-anterior 0.46 vs 0.24 (p = 0.02). Hemodynamic force analysis conveys information of pathological cardiac pumping mechanisms complementary to more established volumetric and functional parameters in precapillary pulmonary hypertension. The right ventricle compensates for the increased afterload in part by augmenting transverse forces, and left ventricular hemodynamic abnormalities are mainly a result of underfilling rather than intrinsic ventricular dysfunction.

Kawasaki Disease with Unusual Systemic Arterial Aneurysms.

HomeRadiologyVol. 306, No. 3 PreviousNext Reviews and CommentaryFree AccessImages in RadiologyKawasaki Disease with Unusual Systemic Arterial AneurysmsXiming Wang, Zhaoping Cheng Ximing Wang, Zhaoping Cheng Author AffiliationsFrom the Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China (X.W.); and Department of Nuclear Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, Shandong, China (Z.C.).Address correspondence to Z.C. (email: [email protected]).Ximing WangZhaoping Cheng Published Online:Nov 8 2022https://doi.org/10.1148/radiol.221084MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In A 23-year-old woman presented with more than a year history of hypertension of unknown origin. Workup with echocardiogram revealed elevation of N-terminal pro–B-type natriuretic peptide, a marker of cardiac dysfunction, and increased left ventricular resistance load. CT angiogram showed multiple unusual aneurysms, including whole course aneurysmal dilatation of the right coronary artery (Figure, A, B), aneurysms of the celiac trunk, and hepatic, splenic, mesenteric, and bilateral renal arteries (Figure, A), as well as bilateral vertebral arteries (Figure, C). Subsequently, the diagnosis of Kawasaki disease with systemic arterial aneurysms was confirmed.CT angiograms in a 23-year-old woman with Kawasaki disease. (A) Cinematic rendering shows multiple aneurysms, including whole course aneurysmal dilatation of the right coronary artery (white arrow) and aneurysms of the hepatic artery (red arrow), splenic artery (yellow arrow), right (green arrow) and left (blue arrow) renal arteries, superior mesenteric artery (purple arrow), and inferior mesenteric artery (orange arrow). (B) Maximum intensity projection shows whole course aneurysmal dilatation of the right coronary artery (arrow). (C) Cinematic rendering shows right (blue arrow) and left (red arrow) vertebral artery aneurysms.Download as PowerPointOpen in Image Viewer Kawasaki disease is an acute vasculitis, usually diagnosed in children between 6 months and 5 years of age. Coronary artery aneurysms are the most recognized complication, seen in approximately 25% of patients without immunoglobulin treatment (1). Rarely, aneurysms of other medium-sized arteries have also been reported (2). Systemic arterial aneurysms, as shown in this case, are uncommon, with a prevalence of 0.8%–2% (3).Disclosures of conflicts of interest: X.W. No relevant relationships. Z.C. No relevant relationships.

Epicardial adipose tissue volume and density is associated with cardiac dysfunction in asymptomatic people with type 2 diabetes

Abstract Background Type 2 diabetes (T2D) is associated with several perturbations of cardiac structure and function, which are precursors to the development of heart failure. Excess accumulation of epicardial adipose tissue (EAT) may contribute to cardiac dysfunction in individuals with T2D. Lipid-laden adipocytes have a lower computed tomography (CT) attenuation and can be readily identified using cardiac CT. Using a multimodality cardiac imaging approach, we aimed to assess the association of total and low attenuation EAT volume with early markers of cardiac dysfunction in people with T2D. Methods Prospective case-control study, in which participants with and without T2D and no known cardiovascular disease, underwent comprehensive cardiovascular phenotyping including multiparametric cardiac magnetic resonance imaging (MRI), echocardiography and non-contrast cardiac CT. EAT volume was measured from CT scans using a deep learning method and volumes indexed to body surface area. Total EAT was defined according to CT adipose tissue attenuation range of −30 to −190 Hounsfield Units (HU) and low attenuation EAT as −90 to −190 HU. Left ventricular (LV) volumes, function and strain measurements were derived from cardiac MRI images and diastolic function also assessed using echocardiography. Markers of early cardiac dysfunction in those with T2D were assessed for associations with EAT in T2D participants using multivariable linear regression analyses. Results Two hundred and fifty-four participants were included: demographic, anthropometric and imaging variables are displayed in Table 1. Subjects with T2D had increased LV concentric remodelling (higher LV mass/volume ratio), diastolic dysfunction (lower circumferential peak early diastolic strain rate (PEDSR) and average E/e') and reduced systolic function (global longitudinal strain, GLS) compared with controls. Total and low attenuation indexed EAT volumes were 1.6-fold and 2-fold higher, respectively, in participants with T2D compared to controls (Figure 1). After adjustment for age, gender, ethnicity, insulin resistance, systolic blood pressure and waist/hip ratio, total and low attenuation indexed EAT volume were independently associated with LV mass/volume ratio (total indexed EAT volume: β=0.002, p=0.02, low attenuation indexed EAT volume: β=0.004, p=0.01) and LV GLS (total indexed EAT volume: β=−0.02, p&amp;lt;0.01, low attenuation indexed EAT volume: β=−0.04, p=0.02) in subjects with T2D, but not indices of diastolic dysfunction. Conclusion Total and low attenuation EAT volumes are higher in individuals with T2D, and excess EAT accumulation is independently associated with early markers of cardiac dysfunction. Further studies into the underlying mechanisms of this interaction may facilitate the development of interventions targeted at EAT, which could mitigate against the development of heart failure in people with T2D. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): United Kingdom National Institute for Health Research

Chronic heart failure as a sequel of severe burn injury: first insight into a novel pathological heart-skin axis

Abstract Research question Our clinical research unveiled chronic heart failure with preserved ejection fraction (HFpEF) as a long-term sequel in survivors of severe pediatric burn injury due to a yet unknown molecular pathomechanism (1). Applying a standardized scald injury rat model, which is widely used in burn research, we systematically determined the pathophysiological impact of burn injury on cardiac performance to uncover systemic and molecular pathomechanisms that may cause post-burn injury HFpEF development. Methods Male adolescent SD-rats were subjected to a 60% total body surface area (TBSA) full-thickness burn- or sham-trauma and subsequently characterized by serial transthoracic echocardiography, bulk myocardial next-generation sequencing and proteomics as well as RT-PCR, immuno-blotting (IB), histology and plasma proteomics for cardiac performance and molecular alterations, for up to 90 days (3, 7, 30 and 90d). Results In comparison to the sham-group (SG, n=10), animals from the burn-group (BG, n=10; survival rate 100%) recapitulated typical post-burn clinical traits, such as significant loss in body weight (BG 27% less than SG at 30d, p&amp;lt;0.05) or skeletal muscle wasting (i.e., 27% less at 30d, p&amp;lt;0.05) in accord with elevated molecular atrophy markers throughout the observation period. Our focus on the heart revealed for the first-time post-burn cardiac muscle wasting (BG 22% less at 30d, p&amp;lt;0.05) and persistent markers of cardiac dysfunction in accord with significant histological cardiomyocyte hypotrophy (BG −8% at 30d, p&amp;lt;0.05) and significantly diminished left ventricular (LV) global longitudinal strain and isovolumic relaxation time in BGs, while LV-EF remained unchanged. Subsequent IB analysis uncovered diminished protein synthesis activity and diminished mTOR pathway activity in BG hearts. Weighted gene network correlation analysis i.e., from bulk myocardial NGS and clinical traits related activation of immunological and pro-fibrotic pathways in post-burn injury hearts to cardiac dysfunction in BGs. Subsequent RT-PCR and histology confirmed significant myocardial accumulation of cardio-depressive damage associated molecular patterns (i.e., S100A8 and A9) and infiltration by granulocytes (myeloperoxidase+) and monocytes (CD 68+) as well as significant LV fibrosis. Serial plasma proteomic analysis indicated elevated plasma levels i.e., of S100A8 and A9 and other heart failure markers that mirrored similar changes in human post-burn injury plasma samples. Conclusion Here we report for the first time the development of HFpEF as a novel systemic consequence of severe burn injury in a rodent model, which prepares the ground for further mechanistic and translational studies. The initial observation of cardiac inflammation and fibrosis, which are known to negatively impact cardiac performance, may be mechanistic key findings that will guide further therapeutic studies and subsequent validation of post-burn heart failure biomarkers. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Rolf-Schwiete Stiftung

Assessment of global longitudinal strain in pediatric survivors of childhood cancer who received cardiotoxic chemotherapy

Cardiotoxicity induced by chemotherapy is the cause of long-term morbidity and mortality, particularly with child exposure. Early detection is essential, as clinical signs are often delayed. In adults, the global longitudinal strain has proven its effectiveness as an early marker of cardiac dysfunction but its place in paediatric management is not yet established. The aim of our study was to analyse the echocardiographic parameters of cardiac function including global longitudinal strain (GLS) in asymptomatic children who received cardiotoxic chemotherapy, at the University Hospital of Amiens, from April to November 2020. The included cases were compared to healthy controls more than one year after their last exposure. We included 22 pediatric childhood cancer survivors and 27 controls with comparable characteristics. The cases had a median age of 11.5 [9.5] years, a median of 3 [1] years from the chemotherapy and a median cumulative anthracycline dose of 234.77 (±105.88) mg/m 2 . Almost a third of our patients were classified as high risk according to CCSS Cardiovascular Risk Calculator score. All myocardial function values were within normal limits. Standard echocardiographic parameters were not different between cases and controls, respectively EF (%) 66.29 (±5.04) vs. 68.14 (±5.37) P < 0.22. As well, Strain 2D values were not significantly different (GLS (%) −20.10 (±2.59) vs. −19.80 (±2.34) P = 0.67). Furthermore, the interobserver reproducibility of GLS was good (intra-class correlation coefficient 0.82 (0.62;0.92) P < 0.01) ( Fig. 1 ). There was no difference of cardiac function echocardiographic parameters, between children who received chemotherapy and controls. There are several limitations, such as the limited number of patients, the monocentric trial and the exclusion of symptomatic patients. The results seem to be in favour of a long free interval between exposure and the onset of altered echocardiographic parameters. Further studies are needed to develop individualised prognostic tools for the follow-up of these patients.

The usefulness of speckle tracking echocardiography in identifying subclinical myocardial dysfunction in young adults recovered from mild COVID-19.

BackgroundMyocardial strain assessed with speckle tracking echocardiography is a sensitive marker of cardiac dysfunction. Both left‐ventricular global longitudinal strain (LV‐GLS) and right ventricular longitudinal strain (RV‐LS) were affected by severe SARS‐CoV‐2 infection. However, data about cardiac involvement in patients with asymptomatic/mild Coronavirus disease‐19 (COVID‐19) is still lacking.AimTo evaluate myocardial function using LV‐GLS and RV‐LS in patients with previous asymptomatic/mild COVID‐19.MethodsForty young adults without previously known comorbidities/cardiovascular risk factors and with a confirmed diagnosis of asymptomatic or paucisymptomatic SARS‐CoV‐2 infection were retrospectively included. A 2D‐transthoracic echocardiogram with speckle tracking analysis was performed at least 3 months after the diagnosis. Forty healthy subjects, matched for age, sex, and body surface area in a 1:1 ratio were used as the control group.ResultsLeft ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE) and RV‐LS were comparable between the two groups. LV‐GLS was significantly lower in the cases compared to the control group (−22.7 ± 1.6% vs. −25.7 ± 2.3%; p < .001). Moreover, the prevalence of regional peak systolic strain below −16% in at least two segments was three times higher in patients with previous COVID‐19 compared to controls (30% vs. 10%, p = .02). In multivariable logistic regression, previous COVID‐19 infection was independently associated with reduced LV‐GLS values (p < .001).ConclusionSARS‐CoV‐2 infection may affect left ventricular deformation in 30% of young adult patients despite an asymptomatic or only mildly symptomatic acute illness. Speckle‐tracking echocardiography could help early identification of patients with subclinical cardiac involvement, with potential repercussions on risk stratification and management.

Diagnosis, management, and outcome of cardiac sarcoidosis and giant cell myocarditis: a Swedish single center experience

BackgroundCardiac sarcoidosis (CS) and giant cell myocarditis (GCM) are rare diseases that share some similarities, but also display different clinical and histopathological features. We aimed to compare the demographics, clinical presentation, and outcome of patients diagnosed with CS or GCM.MethodWe compared the clinical data and outcome of all adult patients with CS (n = 71) or GCM (n = 21) diagnosed at our center between 1991 and 2020.ResultsThe median (interquartile range) follow-up time for patients with CS and GCM was 33.5 [6.5–60.9] and 2.98 [0.6–40.9] months, respectively. In the entire cohort, heart failure (HF) was the most common presenting manifestation (31%), followed by ventricular arrhythmias (25%). At presentation, a left ventricular ejection fraction of < 50% was found in 54% of the CS compared to 86% of the GCM patients (P = 0.014), while corresponding proportions for right ventricular dysfunction were 24% and 52% (P = 0.026), respectively. Advanced HF (NYHA ≥ IIIB) was less common in CS (31%) than in GCM (76%). CS patients displayed significantly lower circulating levels of natriuretic peptides (P < 0.001) and troponins (P = 0.014). Eighteen percent of patients with CS included in the survival analysis reached the composite endpoint of death or heart transplantation (HTx) compared to 68% of patients with GCM (P < 0.001).ConclusionGCM has a more fulminant clinical course than CS with severe biventricular failure, higher levels of circulating biomarkers and an increased need for HTx. The histopathologic diagnosis remained key determinant even after adjustment for markers of cardiac dysfunction.

Cardiac dysfunction in medulloblastoma survivors treated with photon irradiation.

Medulloblastoma is an aggressive central nervous system (CNS) tumor that occurs mostly in the pediatric population. Treatment often includes a combination of surgical resection, craniospinal irradiation (CSI), and chemotherapy. Children who receive standard photon CSI are at risk for cardiac toxicities including coronary artery disease, left ventricular scarring and dysfunction, valvular damage, and atherosclerosis. Current survivorship guidelines recommend routine echocardiogram (ECHO) surveillance. In this multi-institutional study, we describe markers of cardiac dysfunction in medulloblastoma survivors. A retrospective chart review of medulloblastoma patients who had photon beam CSI was followed by ECHO between 1980 and 2010 at Lurie Children's Hospital and Dana-Farber/Boston Children's Hospital. During the 30-year study period, 168 medulloblastoma patient records were identified. Included in this study were the 75 patients who received CSI or spinal radiation and ECHO follow-up. The mean age at CSI was 8.6 years (range, 2.9-20), and the mean number of years between radiation therapy (RT) completion and first ECHO was 7.4 (range, 2-16). Mean ejection fraction (EF) was 60.0% and shortening fraction (SF) was 33.8%. Five patients (7%) had abnormal ECHO results: three with EF <50% and two with SF <28%. The majority of medulloblastoma patients who received CSI have relatively normal ECHOs post-treatment; however, 7% of patients had abnormal ECHOs. The implication of our study for medulloblastoma survivors is that further investigations are needed in this population with a more systematic, longitudinal assessment to determine predictors and screenings.

Adipose-derived stem cell and their extracellular vesicles ameliorates immune function, and cardiac markers in experimental model of cardiorenal syndrome type III: TNF-α, IFN-γ and IL-10 cytokine production and their correlation with genotype

Cardio-renal syndrome (CRS) denotes the convergence of heart-kidney interactions across several mechanisms. The current study is conducted to evaluate the anti-inflammatory role of adipose tissue-derived stem cells (ASCs) versus adipose stem cell-derived extracellular vesicles (ADSCs-EVs) in experimental model of cardiorenal syndrome type III. The study was conducted on 50 male rats that were equally divided to: group I (control group); Group II (experimental cardiorenal syndrome group) which induced by right renal artery ligation (ICRSIII); Group III (Sham-operated control group) which underwent surgical incision without renal artery ligation; Group IV (ICRSIII which received ADSCs-extracellular vesicles (ADSCs-EVs); Group V (ICRSIII which received adipose tissue stem cells (ASCs). Assessment of pro-inflammatory cytokines; IL-10, IL-1α, IL-6, IL-1 β, IFN-γ, NF-α and their mRNA gene expression quantitation, (NGAL), and brain natriuretic peptide (BNP) as markers of cardiac dysfunction, as well as histopathological examination of renal tissue was examined by H& E, Masson trichrome and periodic acid-Schiff stains (PAS). The ICRS group exhibited significant acute tubular injury with tubular dilation, loss of brush borders, epithelial flattening, and occasional sloughed cells in lumen. Use of either ADSCs-EVs or ASCs significantly ameliorated the histological findings of tubular injury. Proinflammatory cytokines, BNP and NGAL were significantly elevated in ICRSIII group as compared to all other studied groups. Administration of ADSCs-EVs or ASCs led to significant decrease in all proinflammatory cytokines as well as BNP and NGAL levels with no significant difference between them. In conclusion, ADSCs-EXs and ASCs exhibited significant repairing effects in experimental-induced cardiorenal syndrome type III as evidenced by amelioration of histological findings of tubular injury, anti-inflammatory effects, and the significant decrease in markers of cardiac dysfunction. ADSC-EVs reprogramed injured cardiac cells by activating regenerative processes.

Association of Atrial Fibrillation Detected after Stroke with Cardiac Dysfunction and Features of Neurogenic Cardiac Injury

ObjectivesUnderstanding the link between markers of cardiac injury and atrial fibrillation (AF) detected after stroke (AFDAS) may help refine stroke risk stratification and therapeutic approaches in AFDAS. Materials and methodsWe retrospectively analyzed 988 adult patients admitted for acute ischemic stroke and transient ischemic attack, who presented within 4.5 h from last known well. Pertinent clinical variables including features of neurogenic cardiac injury (so-called stroke heart syndrome [SHS]) as well as electrocardiographic and echocardiographic markers of cardiac dysfunction, and AF status (no AF n = 574; known AF n = 311; AFDAS; n = 103) were collected. Multivariable logistic regression was used to determine the independent associations of variables with AFDAS. ResultsA total of 264 (26.7%) subjects fulfilled criteria for SHS. Of these, 174 of had SHS features other than AFDAS (non-AF SHS). Among 677 subjects without known AF, presence of non-AF SHS was associated with a 5-fold odds of AFDAS (OR 5.0, 95%-CI 3.1–8.0, p < 0.001). After adjustment, non-AF SHS (OR 3.2, 95%-CI 1.6–6.4, p = 0.001) and the left atrial volume index (OR 1.04, 95%-CI 1.01–1.08, p = 0.004) remained independently associated with AFDAS. ConclusionsThe presence of non-AF SHS features and the left atrial volume index were independently associated with AFDAS indicating diverse mechanisms relating to new onset AF. A better understanding of the links between these markers and AFDAS may help uncover potentially modifiable risk factors for AFDAS as well as aid treatment decisions in patients at risk for new onset AF and ischemic stroke.

Association Between Carotid Atherosclerosis and Atrial Fibrillation, Cardiac, and Renal Function

The aim was to analyse whether the association between carotid atherosclerosis (CA) and atrial fibrillation (AF), heart function, and renal function is mediated by traditional risk factors. In the prospective, single centre, long term, population based Hamburg City Health Study citizens, between 45 and 74 years of age were studied by cross sectional analysis of the first cohort. Laboratory values, blood pressure, heart rhythm, and body mass index (BMI) were examined. Carotid intima media thickness (CIMT) and plaques were assessed by carotid ultrasound, and CA was defined as either CIMT ≥ 1 mm or presence of plaques or both. N-terminal pro-brain natriuretic peptide (NT-proBNP), and glomerular filtration rate (eGFR) were quantified as measures of heart and renal function. Association between CA and AF, NT-proBNP, and eGFR was analysed by multivariable linear and logistic regression. Of the first 10 000 participants, carotid ultrasound was available for 9 466 (95%). Of these, 2 937 (31%) had carotid plaques, 643 (7%) had CIMT ≥ 1 mm, and 412 (4%) presented with both, so that 3 168 (34%) had CA. Participants with CA had AF more frequently (9.6% vs. 4.3%; p < .001), higher levels of NT-proBNP (median 100 vs. 73 pg/mL; p < .001), and lower eGFR (82.8 vs. 87.1 mL/min; p < .001) than those without CA. Adjusted for age and sex, CA was associated with AF (p= .01; OR 1.29) and higher NT-proBNP levels (p < .001; β= 0.12), but not with eGFR. After further adjustment for vascular risk factors and history of cardiovascular diseases, CA remained associated with NT-proBNP (p < .001; β= 0.10), but additionally adjusted for NT-proBNP (p < .001; OR 2.80) not with AF. CA is independently associated with higher levels of NT-proBNP, through common risk factors and NT-proBNP with AF, and not with renal function. CA's association with a marker of cardiac dysfunction beyond known common risk factors supports the value of carotid ultrasound in defining patients' cardiovascular risk profile. The measures of CA, i.e., CIMT and carotid plaque, had an equally directed and additive influence.