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A 3-month-old female weighing 3.6 kg, with trisomy 21, who had undergone pulmonary artery banding for atrioventricular septal defect 2.5 months prior to the presentation was referred to our hospital because of nasal discharge and cough for 3 days and wheezing and decreased feeding for 1 day before

Cardiac dysfunction after subarachnoid hemorrhage (SAH) is described as Takotsubo or reverse Takotsubo cardiomyopathy that shows transient left ventricular wall motion abnormalities with electrocardiogram (ECG) changes. ST change followed by T inversion is a common ECG finding complicated with these disorders, left bundle branch block (LBBB) may be a potential ECG pattern which is seen. In this case, we describe the clinical profile and outcomes of a patient with LBBB and reverse Takotsubo cardiomyopathy after anesthetic induction, which was scheduled as an emergent external ventricular drainage after SAH. This is the first report of an LBBB pattern in reverse Takotsubo cardiomyopathy.

Levosimendan increasingly has been used to treat heart failure and cardiac dysfunction in pediatric patients. Currently, there is only limited evidence that this drug positively affects outcomes. The authors' aim was to investigate the effects of levosimendan on hemodynamic parameters and outcomes in pediatric patients in all clinical settings. The study design was a systematic review of randomized and nonrandomized studies. Randomized clinical trials (RCTs) were included in a meta-analysis. The primary outcome of the meta-analysis was the effect of levosimendan on central venous oxygen saturation (ScvO) and lactate values as surrogate markers of low-cardiac-output syndrome. The study setting was any acute care setting. Study participants were pediatric patients (age

Kidney international 101(2), 256-273 (2022). doi:10.1016/j.kint.2021.10.025, Published by Elsevier, New York, NY

BACKGROUND Extracorporeal membrane oxygenation (ECMO) is a highly invasive procedure and a highcost medical measure, but the economic impact of nosocomial infection after ECMO support remains largely uninvestigated. METHODS We constructed a retrospective cohort of all patients hospitalized at the First Affiliated Hospital of Nanjing Medical University from 2013 to 2020 who had ECMO supported clinical samples. Propensity score matching (PSM) was used to control the impact of potential confounding variables, including demographics, commodities, and treatment, and to estimate the economic burden of nosocomial infection after ECMO support. RESULTS There were 194 patients with ECMO support, 136 patients had no infection after ECMO, 38 patients had infection after ECMO, of which 97.4% was lower respiratory tract infection. Compared with patients among ECMO non infection group, the main reasons for ECMO treatment of patients among ECMO infection group were supportive treatment of cardiac dysfunction (63.16% vs. 42.31%, P=0.021) and longer use of catheter (13.74±14.97 vs. 15.97±14.33 days, P=0.034). The total hospital expenses for patients among ECMO infection group and ECMO non infection group were about $55,878 and $51,277 respectively. Patients with ECMO infection had significantly higher radiate expenses, operational expenses and anesthetic expenses than those among ECMO non infection group ($119.06 vs. $69.32, P=0.025; $6,458.81 vs. $4,882.49, P=0.034; $331.62 vs. $145.56, P=0.030). CONCLUSIONS Our study demonstrates that the incidence of nosocomial infection after ECMO support was relatively high, which did not lead to high total hospital expenses, but lead to higher radiate expenses, operational expenses and anesthetic expenses.

Background Severe burn injury is a specific type of trauma, which induces a unique complex of responses in the body and leads to an extreme increase in stress hormones and proinflammatory cytokines. These hypermetabolic and stress responses are desirable in the acute phase but can persist for several years and lead - due to several mechanisms - to many late complications, including myocardial dysfunction. Methods The databases of PubMed, ScienceDirect, National Institutes of Health (NIH) of the United States, and Google Scholar were searched. Studies relevant to the topic of late cardiovascular dysfunction after burn injury were compiled using key words. Results Burn-induced heart disease significantly increases morbidity and mortality and contributes to the reduction in the quality of life of patients after severe burn trauma. A variety of mechanisms causing myocardial dysfunction after burn trauma have been detailed but understanding all of the exact consequences is limited, especially regarding chronic cardiovascular changes. Conclusion A detailed understanding of the pathophysiology of chronic cardiac changes can contribute to a comprehensive and preventive treatment plan and improve long-term outcomes of burn patients.

Aims Pre-excitation syndrome can lead to recurrent supraventricular tachycardias (SVTs) and carries a risk of sudden cardiac death (SCD). However, an underestimated consequence of antegrade conduction through an accessory pathway is fusion of intrinsic and accessory conduction that causes asynchronous activation and myocardial contraction that could be a cause for cardiac dysfunction and dilation. It is not known to what extent pre-excitation affects myocardial and physical performance in those patients. The aim of the study was to assess to what degree ventricular pre-excitation affects physical performance in children, using cardio-pulmonary exercise testing (CPET). Methods and results The study group consisted of 30 asymptomatic children, aged 8–17 years, with pre-excitation and no history or documentation of SVT compared to 31 healthy controls matched according to sex and age. All patients underwent routine cardiology assessment and then CPET. Echocardiography showed there were no differences in the left ventricular size and function between the study and control group. During the CPET both, patients and controls achieved maximal effort. Patients in the study group showed significantly lower values of VO2max and anaerobic threshold when compared to controls. The most affected subgroup was patients with persistent pre-excitation throughout the exercise. Conclusions Physical performance is affected in children with pre-excitation. This effect is stronger in patients with persistent delta wave observed throughout the exercise.

Background: The use of extracorporeal membrane oxygenation (ECMO) in coronavirus disease 2019 (COVID-19) for refractory respiratory failure, severe cardiac dysfunction, and bridge to lung transplantation has been steadily increasing during the ongoing global pandemic. Objective: Our meta-analysis aims to compare the clinical characteristics between COVID-19 survivors and nonsurvivors requiring ECMO support. Methods: A systematic search of Pubmed, Cochrane, Embase, Scopus, and Web of Science databases was performed between December first, 2019, to June first, 2021. Studies with comparative data of COVID-19 ECMO patients were selected, in which clinical characteristics and complications were assessed. Results: Sixteen cohort studies involving 706 COVID-19 patients requiring ECMO support with pooled mortality rate of 40% were included. Younger age (mean 51 years vs 55 years; P

Aims/Introduction Diabetes mellitus is a major risk factor for the development of cardiovascular diseases. Heart failure with preserved ejection fraction is characterized by left ventricular diastolic dysfunction (LVDD). It has been reported that excess cortisol found in patients with Cushing's syndrome was associated with the development of LVDD. However, the relationship between cortisol concentration and LVDD in patients with diabetes mellitus has not been addressed. Materials and Methods We enrolled 109 patients with diabetes mellitus and 104 patients without diabetes mellitus who had undergone echocardiographic examination at Kyushu University Hospital, Fukuoka, Japan, between November 2016 and March 2019. Left ventricular function was evaluated and the ratio of early diastolic velocity from transmitral inflow to early diastolic velocity (E/eʹ) was used as an index of diastolic function. Plasma cortisol concentrations, glycemic control, lipid profiles, treatment with antidiabetic drugs and other clinical characteristics were evaluated, and their associations with E/eʹ were determined using univariate and multivariate analyses. Results Multivariate linear regression analysis showed that log E/eʹ was positively correlated with age (P = 0.017), log systolic blood pressure (P = 0.004) and cortisol (P = 0.037), and negatively correlated with estimated glomerular filtration rate (P = 0.016) and the use of sodium–glucose cotransporter 2 inhibitors (P = 0.042) in patients with diabetes mellitus. Multivariate analysis showed that cortisol was positively correlated with age (P = 0.016) and glycated hemoglobin (P = 0.011). There was no association between E/eʹ and cortisol in patients without diabetes mellitus. Conclusions Increased cortisol levels might increase the risk of developing LVDD in diabetes mellitus patients.

Pulmonary embolism (PE) is a rare presentation in the pediatric population. We report a case of submassive PE in an adolescent female following commencement of a combined oral contraceptive pill (COCP). In the setting of cardiac dysfunction, she received systemic thrombolysis with significant reduction of clot burden and clinical improvement objectively demonstrated shortly thereafter. This case highlights challenges in clinical decision-making regarding surgical or catheter-based interventions versus medical management approaches when addressing life-threatening PE in children. Our case demonstrates that submassive PE in pediatrics can be managed successfully with systemic thrombolysis and therapeutic anticoagulation.

Preoperative cardiac functional assessment has been a long-debated topic in liver transplantation. Debate continues to exist regarding the use of invasive cardiac studies, and the utility of each prior to transplant. Despite the debate, a 7% mortality can be attributed to significant cardiac events. We present a case series of 3 patients who underwent orthotopic liver transplantation and developed significant cardiac dysfunction postoperatively. All preoperative cardiac assessments in each patient were normal with no hemodynamically significant abnormalities. Interestingly enough, each patient developed cardiac failure due to completely different diagnoses.

Methamphetamine-associated cardiomyopathy (MACM) in an increasingly prevalent disease yet presenting clinical characteristics have not been well studied. We studied consecutive patients with MACM presenting between June 2018 and March 2020 who were interviewed for drug use and medical history. We retrospectively identified an age- and gender-matched cohort of Non-MACM (NMACM) patients and compared clinical characteristics. 140 patients (70 MACM and 70 NMACM) were studied. MACM patients were young (49.6 ± 10 years) and predominantly male (94%). Compared to NMACM, MACM patients were more likely to be Caucasian (21% vs 6%, p = 0.007) and homeless (47% vs 7%, p = 0.001). MACM was characterized by lower left ventricular ejection fraction (EF) (p0.001) and greater LV end diastolic volume (LVEDV) (p = 0.024). Right ventricular (RV) dilation was present more often (p = s0.001) and was more often severe (p = 0.03). Among MACM cases, half of the cohort developed MACM within 5 years of starting MA (18% within 1 year). There was no apparent relationship between frequency or amount of MA used weekly with time until heart failure onset. Drug use patterns were not clearly related to the degree of LV structural change however there were more consistent, significant associations with RV and right atrial (RA) size parameters. In conclusion, patients with MACM have more severe myocardial impairment with lower EF, greater LVEDV and RV dilation. Drug use patterns do not clearly impact degree of LV structural changes by echocardiography however may be related to RV and RA size.

Increased left ventricular dilation and reduced systolic function are consistently associated with a poor prognosis and worse clinical outcomes. In this review, we discuss the pathophysiological me...

Background: Anthracycline therapy-related cardiac dysfunction (ATRCD) is the most notorious adverse side-effect of chemotherapy. It has become a significant cardiovascular health concern for long-term cancer survivors. With the emerging concept of subclinical ATRCD and newer diagnostictools (Speckle Tracking Echocardiography (STE) and biomarkers), detecting anthracycline cardiac toxicity at an early stage has become an important step to prevent severe cardiac dysfunction and improve the cardiovascular outcome in cancer survivors. Despite the increasing population at risk in sub-Saharan Africa (SSA), there is no contemporary data in Uganda to address the burden, pathogenesis and risk factors of subclinical ATRCD. This big gap in knowledge has led to a lack of local guidelines for monitoring and management of ATRCD. Methods: SATRACD (Detecting Subclinical Anthracycline Therapy Related Cardiac Dysfunction In Low Income Country) study is an observational prospective cohort study. Three hundred and fifty-three anthracycline naïve cancer patients will be recruited at baseline. Patients are followed up on completion of anthracycline-based chemotherapy and at 6 months after completion of anthracycline therapy. Data on demographics, cancer profile and clinical presentation will be collected at baseline. Comprehensive cardiac assessment will be performed at each visit, including electrocardiogram, conventional echo- cardiography, STE, cardiac and oxidative stress markers. We will be able to determine the incidence of subclinical and clinical ATRCD at 6 months after completion of anthracycline therapy, determine whether hypertension is a major risk factor for ATRCD, evaluate the role of conventional echocardiography parameters, and biomarkers for detecting subclinical ATRCD. Conclusion: This SATRACD study will provide contemporary data on Ugandan cancer patients who have subclinical and clinical ATRCD, help in the development of local strategies to prevent and manage ATRCD, and improve cardiovascular outcome for Ugandan cancer survivors. Keywords: SATRACD study; subclinical anthracycline therapy; cardiac dysfunction; low income country.

Background Echocardiography is a first-line tool for the screening of patients with cardiac dysfunction. However, the mastery of echocardiography requires significant training, and not all medical teams involve an echocardiography specialist. Telemedicine approaches can potentially improve the quality of echocardiography in resource-limited situations. Methods We used a novel tablet-based hand-held ultrasound device that enables tele-ultrasound— a real-time video telecommunication with remote control for ultrasound images. A trainee scanned patients with various cardiovascular diseases and interpreted the images. Subsequently, the same trainee re-scanned the same patients and re-interpreted the same images using tele-ultrasound with an echocardiography specialist. An examination on the same patients by a blinded specialist was considered the gold standard. Results We included 31 patients (median 77 [interquartile range 68–84] years old, 42% women). Mean absolute errors in left ventricular (LV) end-diastolic and end-systolic diameters, visual LV ejection fraction, and tricuspid annular plane systolic excursion decreased significantly after tele-ultrasound advice (5.9 mm, 5.8 mm, 8.6%, and 4.5 to 1.6 mm, 2.8 mm, 0.7%, and 1.8 mm, respectively, all p 50%, 50–35%, or > 35%) and identifying significant valvular heart diseases. Conclusion Real-time tele-ultrasound improved a trainee’s echocardiography results to those of a specialist-level examination. This approach might be helpful in resource-limited medical teams where echocardiographic specialists are not readily available.

Objective: This study aimed to evaluate the association of Cardiac dysfunction assessed by Echocardiogram study, ferritin, c-reactive protein, and leukocyte count with unfavorable outcomes in pediatric sepsis within the pediatric intensive care unit.Methods: A prospective cohort study was carried out from September 2019 to April 2020, with 40 patients admitted to a pediatric intensive care unit(PICU) at Minia University Children and Maternal hospital, aged between 28 days and 15 years. Inclusion criteria where patients diagnosed with sepsis, need for mechanical ventilation for quite 48h, and vasoactive drugs. Serum levels of C-reactive protein, ferritin, and leukocyte count were collected within 24 h of admission (D1), and 72 h (D3) after admission to PICU. Patients underwent echocardiography study to figure out the ejection fraction of the ventricle on D1 and D3. The outcomes measured through length of stay at hospital and at the pediatric intensive care unit, mechanical ventilation(MV) duration, free hours of VM, duration of use of inotropic agents, maximum inotropic score, and mortality.Results: Patients with elevated ferritin levels on D1 had less ventilator-free time and higher maximum inotropic score. Patients with cardiac dysfunction by echocardiogram on D1 had longer hospital stay pediatric intensive care unit, stay longer duration of mechanical ventilation higher maximum inotropic score, and fewer ventilator-free hoursConclusion: Cardiac dysfunction by echocardiography study and serum ferritin value was significantly related to unfavorable outcomes in pediatric patients requiring admission to PICU with sepsis.

Background: B2-microglobulin (B2M) is recognized as a surrogate marker of middle-molecule uraemic toxins and is a key component in the genesis of dialysis-associated amyloidosis. Objectives: To investigate the relation between hidden cardiac dysfunction in one side and B2M levels, conventional risk factors low hemoglobin levels, and aging on the other side. Subjects and methods: This was a case control study conducted on 50 patients aged 20-60 years with ESRD on regular HD and 50 apparently healthy individuals at El- Mokattam Insurance Hospital from September 2019 till March 2020. Results: There were statistically significant differences between groups regarding B2M, EF, LVMI, intraventricular septal thickness and LVEDD. There were no statistically significant differences between groups. Patient’s B2- microglobulin in Group (A) ranged between 76.00-109.70 with mean±S.D. 94.162±9.735, while in Group (B) ranged between 0.78-3.29 with mean±S.D. 1.956±0.704. There were statistically significant differences between groups. Patient’s LVMI in Group (A) ranged between 111.87-131.59 with mean±S.D. 123.41±5.675, while in Group (B) ranged between 82.02-104.84 with mean±S.D. 91.63±7.236. There were statistically significant differences between groups. Patient’s LVEDD in Group (A) ranged between 5.94-7.56 with mean±S.D. 6.79±0.505, while in Group (B) ranged between 3.27-5.25 with mean±S.D. 4.25±0.571. There were statistically significant differences between groups. Patient’s LVESD in Group (A) ranged between 4.80-5.73 with mean±S.D. 5.34±0.250, while in Group (B) ranged between 2.87-3.65 with mean±S.D. 3.27±0.243. There were no statistically significant differences between groups. Conclusion: Plasma B2M level was significantly and directly correlated with some cardiac performance factors such as LVMI, LVEDD, and LVESD. It was also significantly and inversely associated with GFR, albumin and Hb.

Mouse models of cardiac disease have become essential tools in the study of pathological mechanisms, but the small size of rodents makes it challenging to quantify heart function with noninvasive imaging. Building off recent developments in high-frequency four-dimensional ultrasound (4DUS) imaging, we have applied this technology to study cardiac dysfunction progression in a murine model of metabolic cardiomyopathy. Cardiac knockout of carnitine palmitoyltransferase 2 (

Acute pancreatitis (AP) is one of the common acute abdominal inflammatory diseases in clinic with acute onset and rapid progress. About 20% of the patients will eventually develop into severe acute pancreatitis (SAP) characterized by a large number of inflammatory cells infiltration, gland flocculus flaky necrosis and hemorrhage, finally inducing systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Pancreatic enzyme activation, intestinal endotoxemia (IETM), cytokine activation, microcirculation disturbance, autonomic nerve dysfunction and autophagy dysregulation all play an essential role in the occurrence and progression of SAP. Organ dysfunction is the main cause of early death in SAP. Acute kidney injury (AKI) and acute lung injury (ALI) are common, while cardiac injury (CI) is not, but the case fatality risk is high. Many basic studies have observed obvious ultrastructure change of heart in SAP, including myocardial edema, cardiac hypertrophy, myocardial interstitial collagen deposition. Moreover, in clinical practice, patients with SAP often presented various abnormal electrocardiogram (ECG) and cardiac function. Cases complicated with acute myocardial infarction and pericardial tamponade have also been reported and even result in stress cardiomyopathy. Due to the molecular mechanisms underlying SAP-associated cardiac injury (SACI) remain poorly understood, and there is no complete, unified treatment and sovereign remedy at present, this article reviews reports referring to the pathogenesis, potential markers and treatment methods of SACI in recent years, in order to improve the understanding of cardiac injury in severe pancreatitis.

Despite recent advances in imaging for myocardial deformation, left ventricular ejection fraction (LVEF) is still the most important index for systolic function in daily practice. Its role in multiple fields (e.g., valvular heart disease, myocardial infarction, cancer therapy-related cardiac dysfunction) has been a mainstay in guidelines. In addition, assessment of LVEF is vital to clinical decision-making in patients with heart failure. However, notable limitations to LVEF include poor inter-observer reproducibility dependent on observer skill, poor acoustic windows, and variations in measurement techniques. To solve these problems, methods for standardization of LVEF by sharing reference images among observers and artificial intelligence for accurate measurements have been developed. In this review, we focus on the standardization of LVEF using reference images and automated LVEF using artificial intelligence.

Aims Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function. Methods and results Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg–/– mice). In 9- to 10-week-old hUgcg–/– mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg–/– mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg–/– mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors. Conclusions Our findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function., Graphical Abstract Cardiac glycosphingolipids are required to maintain β-adrenergic signaling and contractile capacity in cardiomyocytes and to preserve normal heart function.

Purpose of review It is now recognized that more than half of patients with acute pulmonary embolism (APE) will have persistent symptoms beyond 3 months after their initial event. Persistent symptoms are referred to as post-PE syndrome, an umbrella term that covers a spectrum of patient complaints and underlying pathologies. Data published over the last 5 years have added significantly to our understanding of this syndrome and its management. Recent findings Underlying pathologies linked to post-PE syndrome include chronic thromboembolic pulmonary hypertension (CTEPH), chronic thromboembolic disease (CTED), cardiac dysfunction, and deconditioning. Treatment for post-PE syndrome will depend on the underlying causative pathologies found. Evaluation and treatment for CTEPH is well defined, but less than 10% of patients with post-PE syndrome will qualify as having this diagnosis. Summary A large percentage of patients will experience post-PE syndrome following APE. Strategies for identification and treatment for some pathologies are well studied, but the majority of patients will have subtle abnormalities on imaging and functional testing for which diagnostic criteria and management are not well defined. A number of active studies are designed to help optimize the management of post-PE syndrome and should help us improve intermediate and long-term outcomes for patients following APE.

Aims Cardiac malfunctions developing in result of sepsis are hard to treat so they eventually contribute to the increased mortality. Previous reports indicated for therapeutic potential of exogenous ω‐3 polyunsaturated fatty acids (PUFA) in sepsis, but potential benefits of this compound on the malfunctional heart have not been explored yet. In the present study, we investigated whether the constantly elevated levels of endogenous ω‐3 PUFA in transgenic fat‐1 mice would alleviate the lipopolysaccharide (LPS)‐induced cardiac failure and death. Methods and results After both wild type (WT) and transgenic fat‐1 mice were challenged with LPS, a Kaplan–Meier curve and echocardiography were performed to evaluate the survival rates and cardiac function. Proteomics analysis, RT‐PCR, western blotting, immune‐histochemistry, and transmission electron microscopy were further performed to investigate the underlying mechanisms. Results showed that transgenic fat‐1 mice exhibited the significantly lower mortality after LPS challenge as compared with their WT counterparts (30% vs. 42.5%, P

Myocardial ischemia/reperfusion (MI/R) has high morbidity and mortality worldwide, but the underlying mechanisms have not been entirely understood. TRIM27 is one of the Tri-domain proteins (TRIM) family proteins with crucial roles in numerous life processes. In the study, we attempted to explore the effects of heart-conditional knockout of TRIM27 (TRIM27cKO) on MI/R progression both in vivo and in vitro. Our results showed that TRIM27 was strongly decreased in murine hearts with MI/R injury and in cardiomyocytes with hypoxic reoxygenation (HR) treatment. TRIM27cKO could further accelerate the infarction size and cardiac dysfunction in MI/R mice. Function study demonstrated that heart-selective TRIM27 deletion significantly aggravated apoptosis in hearts of MI/R mice through enhancing Caspase-3 activities. Moreover, inflammatory response due to MI/R injury was remarkably exacerbated in TRIM27cKO mice by strengthening nuclear factor κB (NF-κB) activation. In addition, p53 expression levels were dramatically up-regulated in hearts of MI/R mice and cardiomyocytes with HR treatment, which were further aggravated by TRIM27cKO. Intriguingly, we found that TRIM27 could interact with p53 and promote its ubquitination. Of note, suppressing p53 remarkably ameliorated TRIM27cKO-intensified apoptotic cell death and inflammation in HR-treated cardiomyocytes. Taken together, all these findings revealed that TRIM27/p53 axis may be involved in MI/R progression, and thus could be a therapeutic target for this disease treatment.

Cardiomyopathy (CM) is a condition of cardiac dysfunction. It is one of the leading causes of mortality in which both genetic and environmental factors are involved. Cardiotrophin-1 (CT-1) level in plasma is associated with CM. It affects the cardiomyocyte differentiation. To evaluate the expression of CT-1 in cardiomyopathy, this study was done on CM subjects attending the Fatima Memorial Hospital, Lahore, Pakistan, between January and June, 2016. A total of 40 subjects were enrolled who were divided into two groups; CM group (n = 20) and a control group (n = 20). A self-designed questionnaire was filled in by each subject to collect data regarding age, body mass index (BMI) and CM history. RNA was isolated from blood after its quantification, cDNA was prepared and reverse-transcriptase-polymerase chain reaction (RT-PCR) was performed for expression of CT-1. The mean age in CM subjects was 40.1±6.03 years, while it was 35.0±3.7 years in the control group. The mean expression of CT-1 in the CM subjects was 5.2±0.66, while it was 1.00±0.001 in the control group. A highly significant difference was observed in CT-1 expression in the CM group, and expression was significantly correlated with age and BMI in CM subjects.

Background: Traumatic brain injury (TBI) is often associated with cardiac dysfunction, which is a consequence of the brain–heart cross talk. The subendocardial viability ratio (SEVR) is an estimate...

Background Cardiac dysfunction, mainly assessed by biomarker alterations, has been described in COVID-19 infection. However, there are still areas of uncertainty regarding its effective role in disease evolution. Aim of this study was to evaluate early echocardiographic parameters in COVID pneumonia and their association with severity disease and prognosis. Methods An echocardiographic examination was performed within 72 h from admission in 64 consecutive patients hospitalized for COVID-19 pneumonia in our medium-intensity care unit, from March 30th to May 15th 2020. Six patients were excluded for inadequate acoustic window. Results Fifty-eight consecutive patients were finally enrolled, with a median age of 58 years. Twenty-two (38%) were classifiable as severe COVID-19 disease. Eight out of 58 patients experienced adverse evolution (six died, two were admitted to ICU and received mechanical ventilation), all of them in the severe pneumonia group. Severe pneumonia patients showed higher troponin, IL-6 and d-Dimer values. No significant new onset alterations of left and right ventricular systolic function parameters were observed. Patients with severe pneumonia showed higher mean estimated systolic pulmonary artery pressure (sPAP) (30.7 ± 5.2 mmHg vs 26.2 ± 4.3 mmHg, p = 0.006), even if in the normality range values. No differences in echocardiographic parameters were retrieved in patients with adverse events with respect to those with favorable clinical course. Conclusion A mild sPAP increase in severe pneumonia patients with respect to those with milder disease was the only significant finding at early echocardiographic examination, without other signs of new onset major cardiac dysfunction. Future studies are needed to deepen the knowledge regarding minor cardiac functional perturbation in the evolution of a complex systemic disorder, in which the respiratory involvement appears as the main character, at least in non-ICU patients.

Although ventricular pre-excitation via accessory pathways (APs) causes cardiac dysfunction in children and young adults with Wolff–Parkinson–White (WPW) syndrome, the underlying cardiac dysfunction mechanisms are unclear. This study aimed to characterize cardiac dysfunction and clarify sensitive cardiac dysfunction indicators in WPW syndrome patients classified by the APs location with a layer-specific strain analysis. Twenty-four patients with WPW syndrome with a mean age of 14.1 years (6.9–21.6 years) (11 cases: type A with a left-sided AP [WA group], 13 cases: type B with a right-sided AP [WB group]), and 37 age-matched normal controls (N group) were examined. We measured the left ventricle (LV), base-, mid-, and apical-level of circumferential strain (CS), and longitudinal strain (LS) using a layer-specific strain with speckle tracking imaging. Dyssynchrony was also measured based on the timing of the radial strain at each segment. Peak endomyocardial base- and mid-level of CS was lower in both the WA and WB groups compared to the N group. Peak mid-myocardial and epimyocardial base-level of CS and peak mid-myocardial mid-level of CS were lower only in the WB group compared to the N group. Peak LS in all three layers was lower only in the WB group compared to the N group. There was a significant difference between the patient and normal groups for the dyssynchrony index only at the base-level, and there was no significant difference between the groups for LV ejection fraction (EF). Layer-specific strain decreased in more sites in the WB group despite the normal EF value. Layer-specific strains are sensitive indicators for the detection of the early stages of cardiac dysfunction.

The purpose of this review is to provide an overview of the essential role that cardiovascular magnetic resonance (CMR) has in the field of cardio-oncology. Recent findings: CMR has been increasingly used for early identification of cancer therapy related cardiac dysfunction (CTRCD) due to its precision in detecting subtle changes in cardiac function and for myocardial tissue characterization. Summary: CMR is able to identify subclinical CTRCD in patients receiving potentially cardiotoxic chemotherapy and guide initiation of cardio protective therapy. Multiparametric analysis with myocardial strain, tissue characterization play a critical role in understanding important clinical questions in cardio-oncology.

We determined whether North American ginseng (Panax quinquefolius L.) mitigates the effect of angiotensin II on hypertrophy and heart failure. Angiotensin II (0.3 mg/kg) was administered to rats for 2 or 4 weeks in the presence or absence of ginseng pretreatment. The effect of ginseng (10 μg/mL) on angiotensin II (100 nM) – induced hypertrophy was also determined in neonatal rat ventricular myocytes. We also determined effects of ginseng on fatty acid and glucose oxidation by measuring gene and protein expression levels of key factors. Angiotensin II treatment for 2 and 4 weeks induced cardiac hypertrophy as evidenced by increased heart weights, as well as the upregulation of the hypertrophy-related fetal gene expression levels, with all effects being abolished by ginseng. Ginseng also reduced abnormalities in left ventricular function as well as the angiotensin II–induced increased blood pressure. In myocytes, ginseng abolished the hypertrophic response to angiotensin II as assessed by surface area and gene expression of molecular markers of hypertrophy. Ginseng modulated angiotensin II–induced abnormalities in gene expression and protein levels of CD36, CPT1M, Glut4, and PDK4 in vivo and in vitro. In conclusion, ginseng suppresses angiotensin II–induced cardiac hypertrophy and dysfunction which is related to normalization of fatty acid and glucose oxidation.

Transient cardiac dysfunction, or Takotsubo cardiomyopathy, is a well-known complication among patients presenting with neurologic insult, who are described as having takotsubo syndrome. This condition is commonly associated with aneurysmal subarachnoid hemorrhage but has also been described in patients after cerebral surgery or in those with ischemic stroke, seizure, and traumatic brain injury. Current evidence suggests that cardiac dysfunction in these patients is a result of increases in catecholamines that are induced by supraphysiologic levels of sympathetic activity. The cardiac injury is typically reversible and carries a good prognosis, but secondary complications may arise if the diagnosis is not recognized early.

The aim of this study is to investigate myocardial damage in recovering coronavirus disease 2019 (COVID-19) patients with high-sensitivity troponin levels (hsTnT) and echocardiography. In this single-center cohort study, 215 COVID-19 recovered patients were recruited from all over Japan between April and September 2020. Demographic characteristics, hsTnT levels, and echocardiography data were collected for 209 patients, after excluding those without serum samples or good-quality echocardiographic images. The mean (± standard deviation) age was 44 (± 12) years (range: 36-55 years), and 50.7% of the patients were males. The median time interval (interquartile range) from COVID-19 onset to post-recovery examination was 56 days (34-96 days). Seventy-four recovered patients (35.4%) had hsTnT less than detection sensitivity (< 3 pg/mL) and 135 recovered patients (64.6%) had hsTnT ≥ 3 pg/mL. Ejection fraction was more than 50% in all cases. Left ventricular global longitudinal strain (LVGLS) and right ventricular free-wall longitudinal strain (RVFWLS) were reduced in 62 (29.7%) and 8 patients (3.8%), respectively. They were significantly associated with elevated hsTnT levels. In cases with hsTnT above 5 pg/mL, the LVGLS was greatly reduced to 19.0 ± 2.2% (p < 0.001). Multivariate linear regression analysis showed that elevated hsTnT level was an independent predictor of reduced LVGLS (standardized β = -0.34; p < 0.001). In recovered COVID-19 patients, even a slight increase in hsTnT above detection sensitivity was associated with decreased LVGLS. hsTnT and echocardiography may be useful tools to detect myocardial injury in recovered COVID-19 patients.

A doença hepática gordurosa não alcoólica (DHGNA) é considerada a doença hepática crônica mais prevalente em todo o mundo, sendo um importante fator de risco para o desenvolvimento de doenças cardiovasculares. A doença arterial coronariana é reconhecida como a primeira causa do aumento de mortalidade e morbidade em pacientes com DHGNA. No entanto, diversas evidências apontam que a DHGNA não afeta apenas os vasos sanguíneos, mas também a estrutura e função do coração, tanto em adultos quanto crianças, chamando atenção para o fato de o comprometimento cardíaco vir a ser um grande fator de risco para a piora do prognóstico e qualidade de vida dos portadores de DHGNA. Nesta revisão narrativa nós descrevemos a associação entre DHGNA e o comprometimento do coração. Em adição, apresentamos uma visão fisiopatológica envolvida nessa relação.

Purpose of review Cirrhotic cardiomyopathy (CCM) is a well-recognized entity. When patients with CCM encounter challenges such as liver transplantation, overt cardiac dysfunction manifests, leading to morbidity and mortality. Although revised diagnostic criteria for CCM have recently been proposed, these still need to be validated. Recent findings Previous reviews have summarized the mechanisms of CCM, such as abnormalities of the β-adrenergic pathway, cardiac plasma membrane biophysical and biochemical properties, and electrophysiological changes. Cardiomyocyte apoptosis, inflammation, and oxidative stress also play important roles. The present review details further mechanisms of CCM, which include myosin heavy chain isoform shifts and abnormalities in cellular calcium transients. Additionally, we review recent studies on therapeutic strategies. Recent work underscores the importance of CCM in the natural history of the immediate and medium-term postoperative period after liver transplantation. Appropriate management strategies for CCM remain the area of greatest unmet need, requiring much further research. Summary CCM is a clinically relevant syndrome affecting patients with cirrhosis, leading to increased morbidity and mortality. New diagnostic criteria have been recently proposed by an expert working group. The pathogenic mechanisms remain incompletely clarified and optimal management strategies need much further study.

A low appropriate therapy rate indicates that a minority of patients will benefit from their implantable cardioverter defibrillator (ICD). Quantitative measurements from 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) may predict ventricular arrhythmia (VA) occurrence after ICD placement. We performed a prospective observational study and recruited patients who required ICD placement. Pre-procedure image scans were performed. Patients were followed up for VA occurrence. Associations between image results and VA were analyzed. In 51 patients (33 males, 53.9 ± 17.2 years) analyzed, 17 (33.3%) developed VA. Compared with patients without VA, patients with VA had significantly larger values in scar area (17.7 ± 12.4% vs. 7.0 ± 7.9%), phase standard deviation (51.4° ± 14.0° vs. 34.0° ± 15.0°), bandwidth (172.9° ± 39.8° vs. 128.7° ± 49.9°), sum thickening score (STS, 29.5 ± 11.1 vs. 17.8 ± 13.2), and sum motion score (42.9 ± 11.5 vs. 33.0 ± 19.0). Cox regression analysis and receiver operating characteristic curve analysis showed that scar size, dyssynchrony, and STS were associated with VA occurrence (HR, 4.956, 95% CI 1.70-14.46). Larger left ventricular scar burden, increased dyssynchrony, and higher STS quantified by 18F-FDG PET may indicate a higher VA incidence after ICD placement.

To evaluate the utility of cardiac magnetic resonance feature tracking-derived left ventricular strain in assessing cardiac dysfunction and investigate the correlation between left ventricular strain and myocardial T2* in patients with beta-thalassaemia major.Forty-two patients with beta-thalassaemia major, having a mean age of 22.49 ± 8.48 years, and age-matched healthy controls were enrolled in the study. The observer drew regions of interest on the interventricular septum, and T2* decay curves were calculated accordingly. The short-axis cine images were used to derive left ventricular circumferential and radial strains, and the long-axis four-chamber and two-chamber images were used to assess left ventricular longitudinal strain.The mean global left ventricular strains were lower in beta-thalassaemia major patients than the controls (Compared with healthy controls, patients with beta-thalassaemia major, including those with myocardial T2* values of20 ms, showed reduced global left ventricular strains. Left ventricular circumferential strain was positively correlated with myocardial T2*. Left ventricular strain analysis using cardiac magnetic resonance feature tracking may have utility in beta-thalassaemia major assessment.Key FindingsPatients with beta-thalassaemia major, including those with myocardial T2* values of20 ms, had reduced global left ventricular strains.Cardiac T2* showed a weak correlation with left ventricular ejection fraction, while the left ventricular circumferential strain showed a good positive correlation with cardiac T2*.ImportanceLeft ventricular strain using cardiac magnetic resonance feature tracking might be used as an adjunct in assessing cardiac functions in beta-thalassaemia major.

Systemic lupus erythematosus (SLE) often leads to various cardiovascular diseases. We aimed to investigate the value of peak strain dispersion (PSD) in evaluating left ventricular dysfunction in patients with uncomplicated SLE. Eighty-seven female SLE patients and fifty-nine healthy female controls were recruited. The SLE patients were divided into inactive disease (SLE disease activity index (SLEDAI) ≤ 4; n = 48) and active disease (SLEDAI ≥ 5; n = 39) subgroups. Traditional echocardiography and two-dimensional speckle-tracking echocardiography were performed using a GE VividE9 ultrasound diagnostic system and an advanced quantitative analysis EchoPAC workstation (version 201), respectively. The global longitudinal strain (GLS) in the SLE with SLEDAI ≤ 4 group was comparable to that in the control group (− 19.89% vs − 20.7%; P = 0.061). However, GLS was obviously damaged in the SLE with SLEDAI ≥ 5 group compared with that in the control group (− 19.07% vs − 20.7%; P

Background: Right ventricular (RV) dysfunction is common and associated with worse outcomes in patients with coronavirus disease 2019 (COVID-19). In non-COVID-19 acute respiratory distress syndrome, RV dysfunction develops due to pulmonary hypoxic vasoconstriction, inflammation, and alveolar overdistension or atelectasis. Although similar pathogenic mechanisms may induce RV dysfunction in COVID-19, other COVID-19-specific pathology, such as pulmonary endothelialitis, thrombosis, or myocarditis, may also affect RV function. We quantified RV dysfunction by echocardiographic strain analysis and investigated its correlation with disease severity, ventilatory parameters, biomarkers, and imaging findings in critically ill COVID-19 patients. Methods: We determined RV free wall longitudinal strain (FWLS) in 32 patients receiving mechanical ventilation for COVID-19-associated respiratory failure. Demographics, comorbid conditions, ventilatory parameters, medications, and laboratory findings were extracted from the medical record. Chest imaging was assessed to determine the severity of lung disease and the presence of pulmonary embolism. Results: Abnormal FWLS was present in 66% of mechanically ventilated COVID-19 patients and was associated with higher lung compliance (39.6 vs 29.4 mL/cmH2O, P = 0.016), lower airway plateau pressures (21 vs 24 cmH2O, P = 0.043), lower tidal volume ventilation (5.74 vs 6.17 cc/kg, P = 0.031), and reduced left ventricular function. FWLS correlated negatively with age (r = −0.414, P = 0.018) and with serum troponin (r = 0.402, P = 0.034). Patients with abnormal RV strain did not exhibit decreased oxygenation or increased disease severity based on inflammatory markers, vasopressor requirements, or chest imaging findings. Conclusions: RV dysfunction is common among critically ill COVID-19 patients and is not related to abnormal lung mechanics or ventilatory pressures. Instead, patients with abnormal FWLS had more favorable lung compliance. RV dysfunction may be secondary to diffuse intravascular micro- and macro-thrombosis or direct myocardial damage. Trial Registration: National Institutes of Health #NCT04306393. Registered 10 March 2020, https://clinicaltrials.gov/ct2/show/NCT04306393

Preeclampsia (PE) is strongly associated with heart failure (HF) later in life. The aberrant cardiac remodelling is likely initiated or amplified during preeclamptic pregnancy. Aberrant remodelling often persists after delivery and is known to relate strongly to cardiac fibrosis. This review provides an overview of pro- and anti- fibrotic circulating effector molecules that are involved in cardiac fibrosis and their association with PE. Women with PE complicated pregnancies show increased ANG-II sensitivity and elevated levels of the pro-fibrotic factors IL-6, TNF-alpha, TGs and FFAs compared to uncomplicated pregnancies. In the postpartum period, PE pregnancies compared to uncomplicated pregnancies have increased ANG-II sensitivity, elevated levels of the pro-fibrotic factors IL-6, TNF-alpha, LDL cholesterol and leptin, as well as decreased levels of the anti-fibrotic factor adiponectin. The review revealed several profibrotic molecules that associate to cardiac fibrosis during and after PE. The role that these fibrotic factors have on the heart during and after PE may improve the understanding of the link between PE and HF. Furthermore they may provide insight into the pathways in which the relation between both diseases can be understood as potential mechanisms which interfere in the process of cardiovascular disease (CVD). Unravelling the molecular mechanism and pathways involved might bring the diagnostic and therapeutic abilities of those factors a step closer.

Advanced heart failure (HF) is used to characterized patients in HF with severe symptoms, recurrent decompensation and severe cardiac dysfunction. The prevalencekof HFkis approximatelyg1-2% of thecadult population inhdeveloped countries and it will be rising more than 10%pamongapeoplec>70ayears of age, whereas estimated theoprevalence ofcpatients with advanced HF is about 1% until 10%cof thekoverallkHFopopulation. Most ofkthe HF hospitalizationssare due to signs and symptoms of fluidcoverload.Recurrent congestionccould worsen patientssoutcomes.Loopdiureticssare recommended for thectreatmentcofkcongestionqinprHF patient. cHowever,cdiureticvresistanceeispavcommon problem issueiinpacuteqdecompensationtofcadvancedochronicrheartwfailureq(ACHF) patients and established prognostic factor. Some early reports estimated the prevalence of diuretic resistance about 20%-30% in HF population. In this review, we will be discuss how to diagnose the advancedvheartufailurepand the underlying mechanism of diuretic resistancebin HF patients. We also describe pharmacologicalvand non-pharmacologicalstrategies to overcome this issue.

Introduction Premenopausal women with intermediate-high risk HR+ breast cancer often receive near-complete estrogen deprivation with ovarian function suppression concurrent with an AI. Hypoestrogenemia is associated with cardiotoxicity, but the cardiovascular impact of this newer breast cancer treatment is largely unknown. With increases in survival rates and younger women being diagnosed, methods to monitor and predict cardiac damage due to OFS+AI therapy are needed. Left ventricle (LV) ejection fraction is currently used for monitoring cancer treatment-related cardiovascular degradation, and can detect major heart defects, but is insensitive to subclinical left ventricle function. Emerging methods include T1 mapping and estimation of myocardial strain to indicate fibrosis. We propose an extension of these methods by estimating cardiac tissue elasticity using LV wall deformation to drive a biomechanical model. Elasticity is a more functional and direct measurement of tissue response based on structural mechanics driven by patient-specific cardiac magnetic resonance imaging (CMR) data. Elasticity measurements may serve as a predictive biomarker of early AI-induced cardiac changes.MethodsThis study is a retrospective initial proof-of-concept correlative imaging study to an existing clinical study for the use of CMR to detect cardiovascular damage (ESPRIT). Two cohorts of premenopausal breast cancer patients either: (1) undergoing OFS+AI for HR+ breast cancer or (2) triple negative breast cancer (TNBC) patients that have already received chemotherapy, were imaged twice, 3-6 months apart using CINE CMR. TNBC patients serve as the control, with no expectation of further cancer treatment-related cardiac damage. Time steps during passive ventricular diastole were visually selected from CINE CMRs. Each slice was non-rigidly registered to estimate LV deformation during passive filling. Deformation was simulated on a finite element mesh of the LV based on linear elastic transverse isotropic mechanical equilibrium. Using an inverse problem formulation, simulated deformation was compared to model-calculated deformation to estimate the spatial tissue longitudinal and transverse elasticity. Elasticity maps of the LV at initial and final points are compared to determine regional stiffening of the LV wall, to be used as early biomarkers for LV fibrosis. ResultsIn this initial investigation, elasticity maps were analyzed for four patients (n=2 from each cohort). Passive LV tissue stiffening was observed in each AI patient, with 100% and 25% relative increases observed for longitudinal elasticity and 50% increases for transverse elasticity in the basal inferior region, and mid anterior region of the LV in each patient, respectively. No increases in stiffness of the LV were observed for TNBC patients. Ejection fraction remained consistent for all patients. ConclusionIn this proof-of-concept study, we demonstrate that elasticity maps indicate local stiffening of the LV using a biomechanical model-based elasticity imaging method that could be used to indicate cardiac dysfunction in breast cancer patients receiving AIs. Spatial elasticity mapping allows direct observation of structural mechanics to reveal specific areas of LV stiffening. Moving beyond traditional strain imaging, our method yields a functional measure of tissue stiffness to directly indicate cardiac fibrosis. This study demonstrates the use of biomechanical models to interpret CMR and provides potential for use of more advanced constitutive models. Our non-invasive biomechanical model-based elasticity imaging method shows significant promise to indicate early cardiac function deterioration, critical for premenopausal women undergoing extended cancer therapies. Citation Format: Caroline Elizabeth Miller, Jennifer Jordan, Alexandra Thomas, Jared Weis. Predicting cardiac dysfunction in breast cancer patients undergoing aromatase inhibitor treatment using biomechanical model-based elasticity imaging [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-21.

It has been more than 200 years since James Parkinson made the first descriptions of the disease that bears his name. Since then, knowledge about Parkinson’s disease has been improved, and its pathophysiology, diagnosis, and treatments are well described in the scientific and medical literature. However, there is no way to prevent the disease from its progressive nature yet and only its symptoms can be minimized. It is known that the process of neurodegeneration begins before the onset of motor signs and symptoms of the disease, when diagnosis is usually made. Therefore, recognizing manifested non-motor symptoms can make an early diagnosis possible and lead to a better understanding of the disease. Autonomic dysfunctions are important non-motor manifestations of Parkinson’s disease and affect the majority of patients. Importantly, heart failure is the third leading cause of death in people suffering from Parkinson’s disease. Several evidences have shown the correlation between Parkinson’s disease and the preexistence of cardiovascular diseases. Therefore, cardiovascular monitoring and identification of its dysfunctions can have a prodromal role for Parkinson’s disease. This review presents studies of the literature that can lead to a better understanding of Parkinson’s disease with special attention to its relation to heart and cardiovascular parameters.

The aim of this study was to develop an artificial intelligence tool to assess echocardiographic image quality objectively.Left ventricular global longitudinal strain (LVGLS) has recently been used to monitor cancer therapeutics-related cardiac dysfunction (CTRCD) but image quality limits its reliability.A DenseNet-121 convolutional neural network was developed for view identification from an athlete's echocardiographic dataset. To prove the concept that classification confidence (CC) can serve as a quality marker, values of longitudinal strain derived from feature tracking of cardiac magnetic resonance (CMR) imaging and strain analysis of echocardiography were compared. The CC was then applied to patients with breast cancer free from CTRCD to investigate the effects of image quality on the reliability of strain analysis.CC of the apical 4-chamber view (A4C) was significantly correlated with the endocardial border delineation index. CC of A4C900 significantly predicted a 15% relative difference in longitudinal strain between CMR feature tracking and automated echocardiographic analysis. Echocardiographic studies (n =752) of 102 patients with breast cancer without CTRCD were investigated. The strain analysis showed higher parallel forms, inter-rater, and test-retest reliabilities in patients with CC of A4C900. During sequential comparisons of automated LVGLS in individual patients, those with CC of A4C900 had a lower false positive detection rate of CTRCD.CC of A4C was associated with the reliability of automated LVGLS and could also potentially be used as a filter to select comparable images from sequential echocardiographic studies in individual patients and reduce the false positive detection rate of CTRCD.

The present study demonstrates that the down-regulation of peroxisome proliferator-activated receptor-α (PPARα) results in chronic low ambient temperature (LT) exposure-induced cardiac dysfunction and remodeling, emphasizing the therapeutic potential of PPARα activation strategies (e.g. fenofibrate treatment) in LT-associated cardiac injury. Supplementary Information The online version contains supplementary material available at 10.1186/s40779-021-00347-y.

The article describes the current understanding of the takotsubo syndrome concerning the issues of pathogenesis, differential diagnosis with acute coronary syndrome and strategy of management. There is presented our own clinical observation of a patient with an atypical form of cardiac dysfunction and myocardial geometry.

Background - Variants within the alpha-tropomyosin gene (TPM1) cause dominantly inherited cardiomyopathies, including dilated (DCM), hypertrophic (HCM) and restrictive (RCM) cardiomyopathy. Here we investigated whether TPM1 variants observed in DCM and HCM patients affect cardiomyocyte physiology differently.Methods - We identified a large family with DCM carrying a recently identified TPM1 gene variant (T201M) and a child with RCM with compound heterozygote TPM1 variants (E62Q and M281T) whose family members carrying single variants show diastolic dysfunction and HCM. The effects of TPM1 variants (T201M, E62Q or M281T) and of a plasmid containing both the E62Q and M281T variants on single-cell Ca2+ transients (CaT) in HL-1 cardiomyocytes were studied. To define toxic threshold levels, we performed dose-dependent transfection of TPM1 variants. In addition, cardiomyocyte structure was studied in human cardiac biopsies with TPM1 variants.Results - Overexpression of TPM1 variants led to time-dependent progressive deterioration of CaT, with the smallest effect seen for E62Q and larger and similar effects seen for the T201M and M281T variants. Overexpression of E62Q/M281T did not exacerbate the effects seen with overexpression of a single TPM1 variant. T201M (DCM) replaced endogenous tropomyosin dose-dependently, while M281T (HCM) did not. Human cardiac biopsies with TPM1 variants revealed loss of sarcomeric structures.Conclusion - All TPM1 variants result in reduced cardiomyocyte CaT amplitudes and loss of sarcomeric structures. These effects may underlie pathophysiology of different cardiomyopathy phenotypes. (C) 2020 The Authors. Published by Elsevier B.V.

Cardiac dysfunction is a major cause leading to multiple organ failure in sepsis. Beclin-1-dependent autophagy has been evidenced to exert protective effects on hearts in sepsis. However, the mechanisms on how Beclin-1 and autophagy are regulated remains enigmatic. To explore the detailed mechanisms controlling Beclin-1-dependent autophagy in septic heart and whether melatonin could protect against sepsis via regulating cardiac autophagy, adult Sprague-Dawley (SD) rats were subjected to cecal ligation and puncture (CLP) to induce sepsis. Rats were intraperitoneally administrated with 30 mg/kg melatonin within 5-min post-CLP surgery. Our data showed that sepsis induced Becline-1 acetylation and inhibited autophagy in hearts, resulting in impaired cardiac function. However, melatonin treatment facilitated Beclin-1 deacetylation and increased autophagy in septic hearts, thus improved cardiac function. Moreover, melatonin increased the expression and activity of Sirtuin 1 (Sirt1), and inhibition of Sirt1 abolished the protective effects of melatonin on Beclin-1 deacetylation and cardiac function. In conclusion, increased Beclin-1 acetylation was involved in impaired autophagy in septic hearts, while melatonin contributed to Beclin-1 deacetylation via Sirt1, leading to improved autophagy and cardiac function in sepsis. Our study sheds light on the important role of Beclin-1 acetylation in regulating autophagy in sepsis and suggests that melatonin is a potential candidate drug for the treatment of sepsis.

Ischemic heart disease in children may be induced by varied factors, and there is no corresponding systematic treatment up to now. This study aims to investigate the effects of microRNA (miR)-148 on myocardial injury in immature rats with myocardial ischemia-reperfusion (MI/R) injury. In this study, MI/R model was established by ligating the coronary artery of heart. The results showed that miR-148 alleviated myocardial injury and rescued relevant parameters (mean ventricular systolic blood pressure (MAP), left ventricular systolic blood pressure (LVSP), heart rate (HR), creatine kinase-MB (CK-MB), cTn1 and Mb in immature rats with MI/R injury. Besides, miR-148 improved the immune dysfunction induced by MI/R through increasing the number of interleukin (IL)-10+ cells and reducing the number of inducible nitric oxide synthase (iNOS)+ cells. In addition, miR-148 relieved the apoptosis of cardiomyocytes induced by MI/R through inhibiting the expression of Bax and elevating the expression of Bcl-2. Further molecular mechanism indicated that pyruvate dehydrogenase kinase 4 (PDK4) was the downstream target of miR-148, which was further confirmed by dual luciferase reporter assay and related expression detection. Accordingly, silenced PDK4 attenuated cardiac dysfunction, immune disorder and myocardial apoptosis in immature rats and enhanced the ability of antioxidant enzymes. What is more, activated SMAD pathway induced by MI/R injury was then blocked by silenced PDK4. Taken together, our study demonstrated that overexpressed miR-148 relieved cardiac dysfunction, immune disorder and cardiomyocyte apoptosis in immature MI/R rats by PDK4 inhibition, which provided novel targets for MI/R injury treatment.