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ObjectiveTo measure and assess the significance of myocardial extracellular volume (ECV), determined non-invasively by equilibrium contrast cardiovascular magnetic resonance, as a clinical biomarker in health and a number of cardiac diseases of varying pathophysiology.DesignProspective study.SettingTertiary referral cardiology centre in London, UK.Patients192 patients were mainly recruited from specialist clinics. We studied patients with Anderson–Fabry disease (AFD, n=17), dilated cardiomyopathy (DCM, n=31), hypertrophic cardiomyopathy (HCM, n=31), severe aortic stenosis (AS, n=66), cardiac AL amyloidosis (n=27) and myocardial infarction (MI, n=20). The results were compared with those for 81 normal subjects.ResultsIn normal subjects, ECV (mean (95% CI), measured in the septum) was slightly higher in women than men (0.273 (0.264 to 0.282 vs 0.233 (0.225 to 0.244), p<0.001), with no change with age. In disease, the ECV of AFD was the same as in normal subjects but higher in all other diseases (p<0.001). Mean ECV was the same in DCM, HCM and AS (0.280, 0.291, 0.276 respectively), but higher in cardiac AL amyloidosis and higher again in MI (0.466 and 0.585 respectively, each p<0.001). Where ECV was elevated, correlations were found with indexed left ventricular mass, end systolic volume, ejection fraction and left atrial area in apparent disease-specific patterns.ConclusionsMyocardial ECV, assessed non-invasively in the septum with equilibrium contrast cardiovascular magnetic resonance, shows gender differences in normal individuals and disease-specific variability. Therefore, ECV shows early potential to be a useful biomarker in health and disease.

Objective To investigate the correlation between non‐invasive cardiac function monitoring indexes and recent adverse prognosis in patients with STEMI. The hemodynamic indexes with high diagnostic value were selected to construct a new risk prediction model combined with GRACE scores, and the efficiency of the new prediction model was evaluated. Methods STEMI patients who met the inclusion and exclusion criteria were selected. All patients were followed for 6 months of major adverse cardiovascular events (MACE). The non‐invasive cardiac function monitoring indexes were analyzed by univariate and multivariate logistic regression. The ROC curve was used to evaluate the accuracy of non‐invasive cardiac function indexes predicting MACE. Then, a new risk prediction model was established and its prediction efficiency was evaluated by ROC curve. Results Patients were divided into MACE group (N = 69) and non‐MACE group (N = 173), stroke volume (SV), cardiac output (CO), cardiac index (CI), cardiac time intervals (CTI), early diastolic filling rate (EDFR), end‐diastolic volume (EDV), and systemic vascular resistance (SVR) were found to be significant predictors of recent MACE events in STEMI patients. Multivariate logistic regression analysis confirmed that indicators of noninvasive cardiac function were independent predictors. In addition, the combination of SV and CTI with the GRACE score has the potential to enhance the predictive accuracy for MACE. Conclusion Non‐invasive hemodynamic indicators SV, CO, CI, CTI, EDFR, EDV and SVR can not only independently predict the risk of recent MACE in patients with STEMI, but can also be used as joint indicators to significantly improve the predictive ability of GRACE score. This study systematically analyzed non‐invasive cardiac function monitoring indicators and proved that non‐invasive hemodynamic indicators not only have the ability to independently predict the short‐term MACE risk of STEMI patients, but also can be used as combined indicators to significantly improve the predictive ability of GRACE score.

PurposeSeverely ill patients affected by coronavirus disease 2019 (COVID-19) develop circulatory failure. We aimed to report patterns of left and right ventricular dysfunction in the first echocardiography following admission to intensive care unit (ICU).MethodsRetrospective, descriptive study that collected echocardiographic and clinical information from severely ill COVID-19 patients admitted to 14 ICUs in 8 countries. Patients admitted to ICU who received at least one echocardiography between 1st February 2020 and 30th June 2021 were included. Clinical and echocardiographic data were uploaded using a secured web-based electronic database (REDCap).ResultsSix hundred and seventy-seven patients were included and the first echo was performed 2 [1, 4] days after ICU admission. The median age was 65 [56, 73] years, and 71% were male. Left ventricle (LV) and/or right ventricle (RV) systolic dysfunction were found in 234 (34.5%) patients. 149 (22%) patients had LV systolic dysfunction (with or without RV dysfunction) without LV dilatation and no elevation in filling pressure. 152 (22.5%) had RV systolic dysfunction. In 517 patients with information on both paradoxical septal motion and quantitative RV size, 90 (17.4%) had acute cor pulmonale (ACP). ACP was associated with mechanical ventilation (OR > 4), pulmonary embolism (OR > 5) and increased PaCO2. Exploratory analyses showed that patients with ACP and older age were more likely to die in hospital (including ICU).ConclusionAlmost one-third of this cohort of critically ill COVID-19 patients exhibited abnormal LV and/or RV systolic function in their first echocardiography assessment. While LV systolic dysfunction appears similar to septic cardiomyopathy, RV systolic dysfunction was related to pressure overload due to positive pressure ventilation, hypercapnia and pulmonary embolism. ACP and age seemed to be associated with mortality in this cohort.

Glucocorticoid (GC) treatment is a cornerstone in the management of inflammatory diseases and adrenal insufficiency. Chronic GC exposure increases the risk of cardiovascular disease, with higher incidence of left ventricular hypertrophy and myocardial remodelling. Despite prevalent clinical use, the mechanisms underlying GC-induced cardiac pathology remain poorly understood. Here we aimed to characterise a mouse model of GC excess to investigate the effects on cardiac function and remodelling.Adult (8-week old) male C57Bl/6J mice were adrenalectomised and administered either vehicle (1% ethanol) or corticosterone (100 μg/mL) in drinking water for 4 weeks (n=10 per group). After 4 weeks’ cardiac structure and function were investigated by high-resolution ultrasound. 48 h post-imaging, mice were culled by decapitation and blood and hearts harvested for histological (PSR and WGA) and transcriptomic (bulk RNA-sequencing) analysis. In a small pilot-study, anaesthetised mice (n=1 per group) were injected (IV) with 3.7 MBq [68Ga]-FAPI and PET/CT scans performed to determine extent of cardiac fibrosis.Corticosterone significantly increased ejection fraction and decreased end diastolic volume, with a trend towards increased diastolic ventricular wall thickness (P=0.06) compared to vehicle. Histological analyses revealed increased collagen content (PSR) and increased cardiomyocyte size in hearts of corticosterone-treated mice. Transcriptomic analysis of hearts revealed >2000 differentially expressed genes, and enrichment of pathways relating to extracellular matrix remodelling, consistent with the development of fibrosis. To assess non-invasive evaluation of potential GC-induced cardiac fibrosis, [68Ga]-FAPI uptake was analysed, with increased uptake observed in the heart from corticosterone-, but not vehicle-treated mice.This study demonstrates that GC excess, even at a relatively short duration induces cardiac remodelling, in parallel with changes in cardiac function. Future work will explore the transcriptional basis of this remodelling with the aim of identifying the cellular drivers behind fibrosis, in parallel with facilitating improved diagnostics and targeted therapeutic interventions.

Scheme depicts hypothesized decreases of heart and SKM function during aging via ROS and partial reversal by SFN activation of Nrf2 that results in significant restoration of function of both types of muscle. A decline in heart and skeletal muscle function was observed in aged mice, with altered mitochondrial structure and gene expression, accompnied by decreases in mitochondrial complex activity, Nrf2 binding to antioxidant‐responsive DNA elements and physical endurance. The addition of sulforaphane (SFN) to the diet improved these age‐related changes in older mice to levels observed in younger ones. We demonstrated in this paper that SFN alleviates age‐associated oxidative damage and improves mitochondrial and cardiac function as well as physical endurance in old mice. Age‐associated mitochondrial dysfunction and oxidative damage are primary causes for multiple health problems including sarcopenia and cardiovascular disease (CVD). Though the role of Nrf2, a transcription factor that regulates cytoprotective gene expression, in myopathy remains poorly defined, it has shown beneficial properties in both sarcopenia and CVD. Sulforaphane (SFN), a natural compound Nrf2‐related activator of cytoprotective genes, provides protection in several disease states including CVD and is in various stages of clinical trials, from cancer prevention to reducing insulin resistance. This study aimed to determine whether SFN may prevent age‐related loss of function in the heart and skeletal muscle. Cohorts of 2‐month‐old and 21‐ to 22‐month‐old mice were administered regular rodent diet or diet supplemented with SFN for 12 weeks. At the completion of the study, skeletal muscle and heart function, mitochondrial function, and Nrf2 activity were measured. Our studies revealed a significant drop in Nrf2 activity and mitochondrial functions, together with a loss of skeletal muscle and cardiac function in the old control mice compared to the younger age group. In the old mice, SFN restored Nrf2 activity, mitochondrial function, cardiac function, exercise capacity, glucose tolerance, and activation/differentiation of skeletal muscle satellite cells. Our results suggest that the age‐associated decline in Nrf2 signaling activity and the associated mitochondrial dysfunction might be implicated in the development of age‐related disease processes. Therefore, the restoration of Nrf2 activity and endogenous cytoprotective mechanisms by SFN may be a safe and effective strategy to protect against muscle and heart dysfunction due to aging.

The midterm effects of cardiac telocytes (CTs) transplantation on myocardial infarction (MI) and the cellular mechanisms involved in the beneficial effects of CTs transplantation are not understood. In the present study, we have revealed that transplantation of CTs was able to significantly decrease the infarct size and improved cardiac function 14 weeks after MI. It has established that CT transplantation exerted a protective effect on the myocardium and this was maintained for at least 14 weeks. The cellular mechanism behind this beneficial effect on MI was partially attributed to increased cardiac angiogenesis, improved reconstruction of the CT network and decreased myocardial fibrosis. These combined effects decreased the infarct size, improved the reconstruction of the LV and enhanced myocardial function in MI. Our findings suggest that CTs could be considered as a potential cell source for therapeutic use to improve cardiac repair and function following MI, used either alone or in tandem with stem cells.

Although the mechanisms underlying the pathophysiology of long COVID condition are still debated, there is growing evidence that autonomic dysfunction may play a role in the long-term complications or persisting symptoms observed in a significant proportion of patients after SARS-CoV-2 infection. However, studies focused on autonomic dysfunction have primarily been conducted in adults, while autonomic function has not yet been investigated in pediatric subjects. In this study, for the first time, we assessed whether pediatric patients with long COVID present abnormalities in autonomic cardiac function. Fifty-six long COVID pediatric patients (mean age 10.3 ± 3.8 y) and 27 age-, sex-, and body surface area-matched healthy controls (mean age 10.4 ± 4.5y) underwent a standard 12-lead electrocardiography (ECG) and 24-h ECG Holter monitoring. Autonomic cardiac function was assessed by time-domain and frequency-domain heart rate variability parameters. A comprehensive echocardiographic study was also obtained by two-dimensional echocardiography and tissue Doppler imaging. Data analysis showed that pediatric patients with long COVID had significant changes in HRV variables compared to healthy controls: significantly lower r-MSSD (root mean square of successive RR interval differences, 47.4 ± 16.9 versus 60.4 ± 29.1, p  = 0.02), significant higher values VLF (very low frequency, 2077.8 ± 1023.3 versus 494.3 ± 1015.5 ms, p  = 0.000), LF (low frequency, 1340.3 ± 635.6 versus 354.6 ± 816.8 ms, p  = 0.000), and HF (high frequency, 895.7 ± 575.8 versus 278.9 ± 616.7 ms, p  = 0.000). No significant differences were observed between the two groups both in systolic and diastolic parameters by echocardiography.   Conclusion : These findings suggest that pediatric patients with long COVID have an imbalance of cardiac autonomic function toward a relative predominance of parasympathetic tone, as already reported in adult patients with long COVID. Further studies are needed to clarify the clinical significance of this autonomic dysfunction and demonstrate its role as a pathophysiological mechanism of long COVID, paving the way for effective therapeutic and preventive strategies. What is Known: • Long Covid in children has been described globally, but studies have mostly focused on collecting the temporal evolution of persisting symptoms. What is New: • Cardiac autonomic imbalance toward a relative predominance of parasympathetic tone is a mechanism underlying Long Covid in children, as also described in adults.

Cardiovascular involvement in Multisystem Inflammatory Syndrome in Children (MIS-C), a potential consequence of coronavirus disease-2019 (COVID-19), is common. Conventional transthoracic echocardiography (TTE) provides primary data on the function of the left and right ventricles, while Speckle Tracking Echocardiography (STE) is more sensitive. This study aims to assess longitudinal cardiac function using STE in these patients. This longitudinal study was conducted from late 2021 to early 2022 at Imam Hossein Children’s Hospital, Isfahan. Cardiac function was assessed by STE at the time of diagnosis and again two months later. Demographics, clinical characteristics, ECG interpretations, imaging studies, and serum cardiac marker levels were collected. Thirty-five pediatric patients with a mean age of 5.1 years (range: 4 months to 17 years) were included and prospectively followed. Twenty-nine of them, comprising 14 males (48.3%) and 15 females (51.7%), underwent STE and were compared with 29 healthy age- and sex-matched children. Factors related to adverse events included reduced myocardial function, enlarged left atrium or ventricle, and mitral regurgitation (MR). Patients with comorbidities affecting strain measurements were excluded from the strain analyses. A significant difference was observed between the groups in regional strains in the basal and apical septal and middle lateral regions. Global strain rate (GLS) and strain rates were not significantly different but were still lower than the control group. Twenty percent of patients had abnormal GLS but normal left ventricular ejection fraction (LVEF). All patients exhibited reduced segmental myocardial strain in at least one segment. Four out of 26 recovered patients without comorbidities had abnormal GLS at follow-up, despite normal LVEF. STE proves more useful than conventional echocardiography in patients with MIS-C, revealing subclinical cardiac injury in the acute and post-acute phases.

Our aim in this study was to investigate whether there is an association between large-for-gestational age (LGA) fetuses and myocardial performance index (MPI). This is a cross-sectional study conducted from July 2022 to July 2023. Prospectively gathered data from 65 LGA cases and 65 age and gestational-age (GA)-matched controls were analyzed. Presence of polyhydramnios and diabetes were recorded in the study group. Fetal left ventricular mod-MPI, peak systolic velocity (PSV) of E and A waves, umbilical and middle cerebral artery (MCA) pulsatility indexes (PI) were sonographically measured. Association between these sonographic measures and LGA fetuses were sought. The LGA group had 33 diabetic cases (22 GDM and 11 PGDM). The LGA group had greater mod-MPI (0.51 vs. 0.45, p = 0.0048). The LGA group also had prolonged isovolumetric contraction time (ICT), compared to controls (37 ms vs. 33 ms, p = 0.008). ICT was longer in LGA fetuses with non-diabetic mothers (38 ms vs. 33 ms, p = 0.009). LGA fetuses with polyhydramnios but without diabetic mothers had also longer ICT (39 ms vs. 33 ms, p = 0.002). Mod-MPI was similar in controls and LGA without diabetes/LGA with polyhydramnios but without diabetes subgroups. Our results indicate that fetal mod-MPI values are higher in LGA fetuses and ICT is prolonged among LGA fetuses irrespective of presence of maternal diabetes.

Background and purpose The transition to adult services, and subsequent glucocorticoid management, is critical in adults with Duchenne muscular dystrophy. This study aims (1) to describe treatment, functional abilities, respiratory and cardiac status during transition to adulthood and adult stages; and (2) to explore the association between glucocorticoid treatment after loss of ambulation (LOA) and late‐stage clinical outcomes. Methods This was a retrospective single‐centre study on individuals with Duchenne muscular dystrophy (≥16 years old) between 1986 and 2022. Logistic regression, Cox proportional hazards models and survival analyses were conducted utilizing data from clinical records. Results In all, 112 individuals were included. Mean age was 23.4 ± 5.2 years and mean follow‐up was 18.5 ± 5.5 years. At last assessment, 47.2% were on glucocorticoids; the mean dose of prednisone was 0.38 ± 0.13 mg/kg/day and of deflazacort 0.43 ± 0.16 mg/kg/day. At age 16 years, motor function limitations included using a manual wheelchair (89.7%), standing (87.9%), transferring from a wheelchair (86.2%) and turning in bed (53.4%); 77.5% had a peak cough flow <270 L/min, 53.3% a forced vital capacity percentage of predicted <50% and 40.3% a left ventricular ejection fraction <50%. Glucocorticoids after LOA reduced the risk and delayed the time to difficulties balancing in the wheelchair, loss of hand to mouth function, forced vital capacity percentage of predicted <30% and forced vital capacity <1 L and were associated with lower frequency of left ventricular ejection fraction <50%, without differences between prednisone and deflazacort. Glucocorticoid dose did not differ by functional, respiratory or cardiac status. Conclusion Glucocorticoids after LOA preserve late‐stage functional abilities, respiratory and cardiac function. It is suggested using functional abilities, respiratory and cardiac status at transition stages for adult services planning.