Relation of myocardial dysfunction to biomarkers, COVID-19 severity and all-cause mortality.

AIMS: The COVID-19 infection has been described as affecting myocardial injury. However, the relation between left ventricular global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS), disease severity and all-cause mortality in COVID-19 is unclear. METHODS AND RESULTS: The study consisted of 220 patients with COVID-19, including 127 (57.5%) with mild, 43 (19.5%) with moderate and 50 (22.7%) with severe/critical conditions. Myocardial dysfunction was analysed by GLS, GCS and GRS using two-dimensional speckle-tracking echocardiography. Hazard ratios and Kaplan-Meier curves were produced to assess the association between strains and cardiac biomarker indices with a composite outcome of all-cause mortality. With an average follow-up period of 11 days, 19 patients reached the endpoint (death). Significant associations were found for the three strain parameters and the levels of blood urea nitrogen (BUN) (r = 0.206, 0.221 and 0.355, respectively). Cardiac troponin I (cTnI) was closely related to the GLS and GCS (r = 0.240 and 0.324, respectively). In multivariable Cox regression, GCS > -21.6% was associated with all-cause death {hazard ratio, 4.007 [95% confidence interval (CI), 11.347-11.919]}. CONCLUSIONS: GLS, GCS and GRS are significantly related to myocardial dysfunction in patients with COVID-19. Worsening GCS poses an increased risk of death in COVID-19.

Gender and age disparities in small-to-medium arterial stiffness among the Chinese population.

BACKGROUND AND AIMS: Arterial pressure-volume index (API) is a non-invasive tool for assessing small-to-medium-sized arterial stiffness. This study aimed to investigate the potential age- and sex-related differences in the API and explore the practical implications of such differences. METHODS AND RESULTS: The study analysed 7620 subjects for whom API measurements were available. Linear regression and restrictive cubic spline models were used to investigate the associations between potential risk conditions and the API. Additionally, this study employed a backward stepwise regression method to identify the independent factors associated with a high API. Middle-aged to older women had higher API values and a higher prevalence of high API than men in the same age group. However, the opposite was observed among younger individuals, with women having lower API values than men. This study also identified a J-shaped relationship between API and age, where API values began to increase at a certain age and rapidly increased after that. In women, the API started to increase at 31 years of age and rapidly increased after 54 years of age. In men, the API started to increase at 38 years of age, followed by a rapid increase after 53 years of age. CONCLUSION: This study's observation of a significant age-sex interaction in small-to-medium-sized arterial stiffening offers a valuable explanation for cardiovascular disease risk and provides important parameters for using API measurements to evaluate such risk.

Early Diagnosis of Abnormal Left Ventricular Systolic Functions of Rare Pathogenic Titin Mutation Gene Carriers in FHCM by Three-Dimensional Speckle Tracking Echocardiography Combined with Gene Detection.

Objective: This study aimed to explore the early diagnosis of abnormal left ventricular systolic function of rare pathogenic titin (TTN) mutation gene carriers in familial hypertrophic cardiomyopathy (FHCM) by three-dimensional speckle tracking echocardiography (3D-STE) combined with gene detection. Methods: Eighteen members of a Hui nationality family in Ningxia province of China were enrolled in this study in July 2019. The proband was tested with high-throughput sequencing of gene detection technology to detect the whole exome, and the mutation locus of pathogenic TTN gene was analyzed. According to the result, 16 subjects were divided into two groups: carrier group (n = 4) and noncarrier group (n = 12). Related indicators from 2DE were obtained, and myocardial strain indicators from 3D-STE were analyzed by postprocessing software of Tomtec. Strain indicators included global longitudinal strain (GLS), global circumference strain (GCS), global radial strain (GRS), regional longitudinal strain (RLS), regional circumference strain (RCS), and regional radial strain (RRS). All those indicators were compared between the two groups, and a receiver operating characteristic (ROC) curve was used for further analysis. Results: There were 4 subjects diagnosed as asymptomatic TTN gene carriers with the mutation locus of Val135643Ile. Compared with the noncarrier group, GLS and partial RLS were significantly reduced in the carrier group. The ROC curve shows that GLS has the largest AUC, and its sensitivity was better than LVPWD and specificity was better than IVSD and LVMI obtained from 2DE in the carrier group. Conclusions: There were 4 subjects diagnosed as asymptomatic TTN gene carriers with the mutation locus of Val135643Ile, and their GLS and partial RLS were significantly reduced; GLS had the better sensitivity and specificity than LVPWD, IVSD, and LVMI.

Overexpression of PLK1 relieved the myocardial ischemia-reperfusion injury of rats through inducing the mitophagy and regulating the p-AMPK/FUNDC1 axis.

Myocardial cell injury caused by myocardial ischemia and reperfusion is one of the main causes of the occurrence and development of heart disease. Recent study has shown that inducing mitophagy of cardiomyocytes is a crucial method to alleviate ischemia-reperfusion injury. While, Polo-like kinase 1 (PLK1) can induce the mitophagy of breast cancer cells. Moreover, PLK1 was able to promote the expression of p-AMPK and FUNDC1, which are the protective factors for myocardium. Therefore, the mouse model of ischemia/reperfusion was established and the effect of PLK1 on ischemia reperfusion induced myocardial damage was investigated. The PLK1 was overexpressed in H9c2 cells and rat model of ischemia/reperfusion. Ischemia reperfusion inhibited the expression of PLK1. While overexpression of PLK1 relieved the myocardial infarction and myocardium apoptosis through inducing mitophagy in rats model of ischemia reperfusion. In vitro, the H9c2 cells overexpressing the PLK1 were treated with the hypoxia and reoxygenation and the apoptosis, survival rate and expression of mitophagy-related proteins of H9c2 cells were detected using the flow cytometry, CCK-8 assay and western blotting. The results reveled that overexpression of PLK1 alleviated the hypoxia and reoxygenation induced apoptosis of H9c2 cells and promoted the expression of mitophagy-related proteins. In addition, enhanced PLK1 expression promoted the expression of p-AMPK and FUNDC1 in H9c2 cells. However, the inhibition of FUNDC1 abolished the positive effect of PLK1 on H9c2 cells mentioned above. In conclusion, PLK1 alleviated the ischemia reperfusion induced myocardial damage by inducing the mitophagy in a p-AMPK/FUNDC1 signaling dependent pathway.

Selecting the optimal parameters for sonoporation of pancreatic cancer in a pre-clinical model.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the modern world, in part due to poor delivery of chemotherapeutics. Sonoporation can be used to enhance the efficacy of standard of care therapies for PDAC. Using xenograft models of PDAC we investigate sonoporation using four ifferent ultrasound contrast agents (UCAs) and two ultrasound regimens to identify the ideal parameters to increase therapeutic efficacy. MIA-PaCa2 xenografts in over 175 immunodeficient mice were treated with gemcitabine and paclitaxel and subjected to low or high power ultrasound (60 and 200 mW/cm2 respectively) in conjunction with one of four different UCAs. The UCAs investigated were Definity®, SonoVue®, Optison™ or Sonazoid™. Tumor volumes, vascularity, hemoglobin, and oxygenation were measured and compared to controls. High power treatment in conjunction with Sonazoid sonoporation led to significantly smaller tumors when started early (tumors ~50mm3; p = .0105), while no UCAs significantly increased efficacy in the low power cohort. This trend was also found in larger tumors (~250mm3) where all four UCA agents significantly increased therapeutic efficacy in the high power group (p < .01), while only Definity and SonoVue increased efficacy in the low power cohort (p < .03). Overall, the higher power ultrasound treatment modality was more consistently effective at decreasing tumor volume and increasing vascularity characteristics. In conclusion, Sonazoid was the most consistently effective UCA at decreasing tumor volume and increasing vascularity. Thus, we are pursuing a larger phase II clinical trial to validate the increased efficacy of sonoporation in conjunction with chemotherapy in PDAC patients.

Efficient Treatment of Atherosclerosis by Dexamethasone Acetate and Rapamycin Co-Loaded mPEG-DSPE Calcium Phosphate Nanoparticles.

Atherosclerosis (AS) is one of the leading causes of vascular disease, producing high morbidity and mortality in many countries. Autophagy plays an important role when cells are facing serious circumstances, such as oxidative stress induced by Ox-LDL (oxidized low-density lipoprotein). Recent studies have revealed that DEX (dexamethasone acetate) and RAPA (rapamycin) exhibit efficient AS therapeutic ability by protecting endothelial cells and killing foam cells, respectively. Herein, we hypothesize that combining DEX and RAPA together in a specific nanocarrier system can achieve better AS therapy while limiting harmful effects. As a proof of concept, DEX and RAPA coloaded mPEG2k-DSPE calcium phosphate (CaP) nanoparticles (DR-NPs) were prepared by using a biomineralization method. DR-NPs increased HUVEC survival and induced foam cell apoptosis in vitro, which were correlated with autophagy activity. DR-NPs efficiently aggregated at AS plaques in the carotid artery and abdominal artery in ApoE- / - mice 24 h after i.v. injection. Moreover, DR-NPs exhibited excellent plaque regression ability, with smaller necrotic cores and lipid core areas observed after in vivo treatment. Furthermore, the function of vascular endothelial cells was largely promoted, as evidenced by the dramatically decreased expression levels of adhesion factors, such as MMP-2, MMP-9 and ICAM-1. Consequently, DR-NPs can act as an effective AS therapeutic agent and broaden the AS therapeutic approach by inducing autophagy.

Role of PI3K/AKT/mTOR Pathway Associated Oxidative Stress and Cardiac Dysfunction in Takotsubo Syndrome.

INTRODUCTION: Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy, but the accurate cause of this syndrome is still unknown. METHODS: ß-adrenergic agonist isoproterenol (ISO) is used to establish the TTS rats model. TTS rats were treated with or without LY294002 or Rapamycin. The rat cardiomyoblast cell line H9C2 was subjected to infect with constitutively active Akt (myr-Akt) or dominant-negative mutant Akt (dn-Akt) and then, treated with ISO. Cell apoptosis was assessed using the Bax/ Bcl-2 ratio. In addition, reactive oxygen species (ROS) levels were measured using dihydroethidium (DHE). Mitochondrial superoxide generation and membrane potential were assayed by MitoSOX and JC-1 fluorescence intensity. RESULTS: ISO might induce the erratic acute cardiac dysfunction and overexpression of PI3K/AKT/mTOR. Moreover, it also increased the oxidative stress and apoptosis in TTS rats. The Akt inhibitor significantly reversed the cardiac injury effect, which triggered by ISO treatment. In H9C2 cells, the inhibition of Akt provides a protective role against ISO-induced injury by reducing oxidative stress, apoptosis and mitochondrial dysfunction. CONCLUSION: This study provided new insight into the protective effects of myocardial dysfunction in TTS rats via chronic inhibition of the PI3K/AKT/mTOR expression, which could reduce mitochondrial ROS and oxidative stress-induced apoptosis. PI3K/AKT/mTOR inhibitor could be a therapeutic target to treat cardiovascular dysfunction induced by stress cardiomyopathy.

Ultrasound assessment of tensile stress in carotid arteries of healthy human subjects with varying age.

BACKGROUND: Arterial remodeling is thought to reflect the adaptation of the vessel wall to mechanical and hemodynamic stimuli and contributes to the progression of cardiovascular and cerebrovascular diseases. Tensile stress (TS) is one of the mechanical properties of the artery wall. The purpose of this study was to investigate the tensile stress change (TS) of carotid artery with varying viscoelasticity in healthy subjects within two groups of different ages. METHODS: Forty-five subjects were recruited and randomly assigned into the group at the age above 50 years and below 50 years. The carotid arteries were examined by ultrasonography, using the techniques of shear wave elastography (SWE), shear wave dispersion (SWD) and radiofrequency (RF) -based ultrasound. The following values, including elastic modulus (SWER) and viscous index (SWDR), as well as the peak and mean TS of the left and right carotid arteries (L-PTS, R-PTS, L-MTS and R-MTS) were measured. The correlations between SWER, SWDR and tensile stress were evaluated. RESULTS: The SWER and SWDR of carotid arteries are lower in the subjects ≥50 years old than the subjects younger than 50 years (SWER, 10.29 ± 9.57 kPa VS 17.24 ± 14.07 kPa; SWDR, 11.99 ± 3.51 (m/s)/kHz VS 13.97 ± 3.71 (m/s)/kHz, P < 0.05). The R-PTS was lower in the group with younger age (P < 0.05). Pearson correlation analysis showed that SWER of carotid artery was positively correlated with the parameters of tensile stress, R-PTS, R-MTS, L-PTS and L-MTS(r = 0.218, r = 0.359, r = 0.209 and r = 0.369, respectively, P < 0.05). However, SWDR of carotid arteries was not significantly associated with TS. CONCLUSION: Ultrasonic shear wave imaging could be used to quantitatively assess carotid viscoelasticity. The carotid TS was related to its elasticity while little related to its viscosity, suggesting that mechanical properties of the arterial wall might be better revealed. TRIAL REGISTRATION: Date of our trial registration: 2018-06-11. Registered with the official website of China Clinical Trial Registration Center (ChiCTR1800016590).

Ultrasonic risk stratification of carotid web.

Carotid webs may cause a frequent recurrent ischemic stroke. Based on the database of patients with transient ischemic attack (TIA), demographics, clinical, and imaging characteristics were compared between the patients with carotid web and without it. Twelve patients with carotid web were younger and more frequent in females than those without it. Both clinical and imaging features determined that the patients with carotid web were prone to TIA due to the pooling of blood with stagnation and the consequent thrombosis. Ultrasonography has big potential for assessment and risk stratification of the carotid web.

Congenital atresia of the left main coronary artery: Imaging feature in children.

Congenital left main coronary atresia (LMCA) is a rare coronary anomaly associated with myocardial ischemia and sudden death. Echocardiography is an important tool for diagnosis of LMCA. The results of echocardiography and relevant clinical signs were retrospectively analyzed in 3 children with LMCA. Echocardiographic examination showed the signs of LMCA: in left coronary sinus no opening of left coronary artery (LCA), retrograded blood flow in LCA, abound blood flow in ventricular wall, and mild widen RCA.

Ultrasound findings of urachal anomalies. A series of interesting cases.

AIMS: This study's aim is to present the specific ultrasonography (US) findings of a series of urachus anomalies. MATERIAL AND METHODS: Seven patients with suspected urachal anomalies underwent US scanning initially prior to the surgery and the features of images were reviewed respectively. The clinical data and pathologic results were collected also. RESULTS: US successfully diagnosed urachal anomalies in 5 patients (5/7, 71.4%) and failed to diagnose in 2 patients (2/7, 28.6%). Patent urachus showed a tubule between the umbilicus and bladder; urachal sinus was a blind focal dilatation at the umbilical end, while vesicourachal diverticulum was an outpouching at the vesical end and urachal cyst was identified as an anechoic structure along the urachus. Non-enhancement in the base and centre was the distinct features of urachus carcinoma by contrastenhanced ultrasonography (CEUS). Using a high frequency probe and CEUS the diagnostic ability of US may be improved. CONCLUSION: US showed good diagnostic ability in urachal anomalies and combined with CEUS could improve the differential diagnosis.

Relation between carotid vulnerable plaques and peripheral leukocyte: a case-control study of comparison utilizing multi-parametric contrast-enhanced ultrasound.

BACKGROUND: This study evaluates carotid vulnerable plaques using contrast-enhanced ultrasound (CEUS) and explores the relationship between vulnerable plaques and leukocytes. METHODS: Sixty-two symptomatic and 54 asymptomatic patients underwent CEUS. The images were analyzed using time-intensity and fitting curves, and peak (PTIC), mean (MTIC), peak (PFC), sharpness (SFC), and area under the curve (AUCFC) were obtained. The relations between CEUS parameters and leukocytes were analyzed. RESULTS: In the symptomatic group, total leukocytes and neutrophils were higher, while lymphocyte was decreased; PTIC, MTIC, PFC, SFC, and AUCFC were significantly higher; MTIC and AUCFC were negatively correlated with lymphocytes, and MTIC was positively correlated with neutrophils. Classification and regression tree analysis showed that MTIC at a cutoff of 20.8 and AUCFC at a cutoff of 8.8 resulted in a predictive of acute cerebral infarction, accuracy of 84.3%, sensitivity of 87.1%, and specificity of 81.5%. CONCLUSIONS: The variation in the perivascular leucocyte is significantly related to intraplaque inflammatory activities, CEUS is a feasible monitor of intraplaque neovascularization, so CEUS combined with perivascular leucocyte could be helpful as a warning for vulnerable plaques.

Combined transthoracic echocardiography and contrast-enhanced ultrasonography to trace intravenous leiomyomatosis with intracardiac extension.

Intravenous leiomyomatosis (IVL) with intracardiac extension is a rare condition, which the benign tumor invades into the right heart through inferior vena cava. We described the findings of ultrasonography in eight patients with this disease. Transthoracic echocardiography (TTE) can reveal the intracardiac lesion burden and associated compromise. Contrast-enhanced ultrasonography (CEUS) can trace the origin of the lesion and extension. Therefore, combining TTE with CEUS is used to better characterize this complex lesion and plays a crucial role in guidance of surgical decision.

An improvement of carotid intima-media thickness and pulse wave velocity in renal transplant recipients.

BACKGROUND: Renal transplantation can significantly improve the quality of life of patients with end stage renal disease (ESRD) who would otherwise require dialysis. Renal transplant (RT) recipients have higher risks of cardiovascular disease compared with general population. The carotid intima-media thickness (CIMT) and pulse wave velocity (PWV) have been used as the important predicting factor of vascular arteriosclerosis. Therefore, this study was to investigate the improvement of carotid intima-media thickness and pulse wave velocity in renal transplant recipients. METHODS: Thirty-one patients with chronic kidney disease being treated with hemodialysis, 31 renal transplant recipients and 84 healthy control subjects were included to have the clinical evaluations and ultrasonography of bilateral carotid arteries. CIMT and PWV were independently measured by two ultrasonographers using the technique of ultrasonic radiofrequency tracking and correlated with arteriosclerosis risk factors. The progression of CIMT and PWV with age were analyzed by linear regression models, and the slopes of curves were compared using Z test. RESULTS: Compared with the patients on hemodialysis, the CIMT was significantly lower in renal transplant recipients and healthy control. The PWV were higher in hemodialysis patients and renal transplant recipients than that of the subjects in control group. The progression is CIMT positively corelated with age and cumulative duration in renal transplant recipients and hemodialysis patients. In both hemodialysis patients and renal transplant recipients, age and cumulative time on dialysis were all positively correlated with the increase of PWV as well. CONCLUSIONS: Carotid intima-media thickness and pulse wave velocity is the predicting factors of developing arteriosclerosis, which were improved in renal transplant recipients.

Ultrasound Assessment of Intima-media Thickness and Diameter of Carotid Arteries in Patients Undergoing Hemodialysis or Renal Transplantation.

Renal transplant (RT) recipients have a high risk of developing cardiovascular diseases. However, the effects of renal transplantation on the development of arteriosclerosis have been controversial. The carotid intima-media thickness (СШТ) and diameter (CD) are important indicators of vascular remodeling and arteriosclerosis. In this study, 31 patients with hemodialysis (HD), 31 RT recipients and 84 age- and gender-matched control subjects were enrolled. Their CIMT and CD were measured by ultrasonic radiofrequency tracking, and the linear regression models and Z test were used to identify the progression of arteriosclerosis and the risk factors. Compared with HD group, RT group had significantly lower CIMT and CD. CIMT was found to be associated with age, body weight, resistance index and diastolic velocity, while CD was associated significantly with age, body weight, pulsatility index, end diastolic velocity and diastolic blood pressure (DBP), respectively. The correlation curves between CIMT and age showed the slopes of curves were decreased successively in control, RT and HD groups, and the curves between CD and age showed the slopes were decreased in order of RT > control > HD groups. It was concluded that CIMT and CD were significantly correlated with age in RT and moderately with age in HD patients. RT could reduce the progress of arteriosclerosis in patients with end-stage renal disease.

Carotid vulnerable plaques are associated with circulating leukocytes in acute ischemic stroke patients: an clinical study based on contrast-enhanced ultrasound.

Inflammatory activity plays a central role in the development of carotid rupture-vulnerable atherosclerotic plaques, which is one of the major contributors to acute ischemic stroke. Our objective was to characterize carotid intraplaque neovascularizations (INP) using contrast-enhanced ultrasound (CEUS) and evaluate plaque burden through exploring the relationship between INP and cell count of peripheral leukocytes. Sixty-two patients with large artery atherosclerosis (LAA) were enrolled in this study. CEUS was performed to characterize the carotid artery plaques. The correlations between the CEUS imaging features of carotid plaques and leukocyte counts were investigated. The results showed that the characteristic parameters derived from CEUS, including peak of time-intensity curve (TIC-P), mean of time-intensity curve (TIC-M), peak (FC-P), sharpness (FC-S) and area under the curve (FC-AUC) compared with the control group, were all increased in the stroke group. TIC-P, TIC-M and FC-P were negatively related to lymphocytes, respectively. FC-S and FC-AUC were positively correlated with neutrophils, respectively. Our study indicated carotid INP was closely related to the peripheral leukocytes count. CEUS may serve as a useful tool to predict vulnerability of plaque.

Evaluation of left atrial volume and function using single-beat real-time three-dimensional echocardiography in atrial fibrillation patients.

BACKGROUND: This study was aimed to evaluate the feasibility and accuracy of real-time three-dimensional echocardiography (RT-3DE) measurement of left atrial (LA) volume and function in comparison with two-dimensional echocardiography (2DE) measurements in atrial fibrillation (AF) patients. METHODS: A total of 50 pairs of AF patients and healthy controls were enrolled in this study. Indexed LA end-diastole volume (ILAEDV) and indexed LA end-systolic volume (ILAESV), as well as LA function indices such as segmental LA ejection fraction (LAEF), were assessed using 2DE Simpson's method and the RT-3DE method. RESULTS: The images showed that regional LA volume-time curves and LAEF were disordered in AF patients. ILAEDV and ILAESV were markedly increased and global LAEF was significantly decreased in AF patients compared with those in healthy controls (P < 0.01). No significant differences were found in ILAEDV, ILAESV, and LAEF levels as determined by the RT-3DE method or 2DE Simpson's method. Bland-Altman analysis showed that the two methods agreed well for measuring ILAEDV, ILAESV, and segmental LAEF. CONCLUSION: The RT-3DE method may be a feasible and accurate method for evaluating LA volume and function of AF patients in clinical practice.