CD151 Maintains Endolysosomal Protein Quality to Inhibit Vascular Inflammation.

BACKGROUND: Tetraspanin CD151 is highly expressed in endothelia and reinforces cell adhesion, but its role in vascular inflammation remains largely unknown. METHODS: In vitro molecular and cellular biological analyses on genetically modified endothelial cells, in vivo vascular biological analyses on genetically engineered mouse models, and in silico systems biology and bioinformatics analyses on CD151-related events. RESULTS: Endothelial ablation of Cd151 leads to pulmonary and cardiac inflammation, severe sepsis, and perilous COVID-19, and endothelial CD151 becomes downregulated in inflammation. Mechanistically, CD151 restrains endothelial release of proinflammatory molecules for less leukocyte infiltration. At the subcellular level, CD151 determines the integrity of multivesicular bodies/lysosomes and confines the production of exosomes that carry cytokines such as ANGPT2 (angiopoietin-2) and proteases such as cathepsin-D. At the molecular level, CD151 docks VCP (valosin-containing protein)/p97, which controls protein quality via mediating deubiquitination for proteolytic degradation, onto endolysosomes to facilitate VCP/p97 function. At the endolysosome membrane, CD151 links VCP/p97 to (1) IFITM3 (interferon-induced transmembrane protein 3), which regulates multivesicular body functions, to restrain IFITM3-mediated exosomal sorting, and (2) V-ATPase, which dictates endolysosome pH, to support functional assembly of V-ATPase. CONCLUSIONS: Distinct from its canonical function in strengthening cell adhesion at cell surface, CD151 maintains endolysosome function by sustaining VCP/p97-mediated protein unfolding and turnover. By supporting protein quality control and protein degradation, CD151 prevents proteins from (1) buildup in endolysosomes and (2) discharge through exosomes, to limit vascular inflammation. Also, our study conceptualizes that balance between degradation and discharge of proteins in endothelial cells determines vascular information. Thus, the IFITM3/V-ATPase-tetraspanin-VCP/p97 complexes on endolysosome, as a protein quality control and inflammation-inhibitory machinery, could be beneficial for therapeutic intervention against vascular inflammation.

Downregulation of the CD151 protects the cardiac function by the crosstalk between the endothelial cells and cardiomyocytes via exosomes.

BACKGROUND: Heart failure (HF) is the last stage in the progression of various cardiovascular diseases. Although it is documented that CD151 contributes to regulate the myocardial infarction, the function of CD151 on HF and involved mechanisms are still unclear. METHOD AND RESULTS: In the present study, we found that the recombinant adeno-associated virus (rAAV)-mediated endothelial cell-specific knockdown of CD151-transfected mice improved transverse aortic constriction (TAC)-induced cardiac function, attenuated myocardial hypertrophy and fibrosis, and increased coronary perfusion, whereas overexpression of the CD151 protein aggravated cardiac dysfunction and showed the opposite effects. In vitro, the cardiomyocytes hypertrophy induced by PE were significantly improved, while the proliferation and migration of cardiac fibroblasts (CFs) were significantly reduced, when co-cultured with the CD151-silenced endothelial cells (ECs). To further explore the mechanisms, the exosomes from the CD151-silenced ECs were taken by cardiomyocyte (CMs) and CFs, verified the intercellular communication. And the protective effects of CD151-silenced ECs were inhibited when exosome inhibitor (GW4869) was added. Additionally, a quantitative proteomics method was used to identify potential proteins in CD151-silenced EC exosomes. We found that the suppression of CD151 could regulate the PPAR signaling pathway via exosomes. CONCLUSION: Our observations suggest that the downregulation of CD151 is an important positive regulator of cardiac function of heart failure, which can regulate exosome-stored proteins to play a role in the cellular interaction on the CMs and CFs. Modulating the exosome levels of ECs by reducing CD151 expression may offer novel therapeutic strategies and targets for HF treatment.

[Corrigendum] The tetraspanin CD151­ARSA mutant inhibits angiogenesis via the YRSL sequence.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 4A on p. 839, the 'CD151/24 h' and 'CD151­ARSA/48 h' panels appeared to contain overlapping sections of data, such that they were potentially derived from the same original source, where these panels were intended to show the results from differently performed experiments. The authors have re­examined their original data, and realize that the 'CD151­ARSA/48 h' panel was inadvertently placed incorrectly in the figure. The revised version of Fig. 4, now containing the correct data for the 'CD151­ARSA/48 h' experiment in Fig. 4A, is shown below. Note that this error did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 7: 836­842, 2013; DOI: 10.3892/mmr.2012.1250].

Expression profiles and potential functions of microRNAs in heart failure patients from the Uyghur population.

BACKGROUND AND PURPOSE: Existing studies have shown that circulating miRNA can be used as biomarkers of heart failure (HF). However, the circulating miRNA expression profile in Uyghur HF patients is unclear. In this study, we identified the miRNA profiles in the plasma of Uyghur HF patients and preliminarily explored their potential functions to provide new ideas for the diagnosis and treatment of HF. METHODS: Totally, 33 Uyghur patients with HF with reduced ejection fraction (<40%) were included in the HF group and 18 Uyghur patients without HF were included in the control group. First, high-throughput sequencing was used to identify differentially expressed miRNAs in the plasma of heart failure patients (n = 3) and controls (n = 3). Second, the differentially expressed miRNAs were annotated with online software and bioinformatics analysis was used to explore the critical roles of these circulating miRNAs in HF. Moreover, four selected differentially expressed miRNAs were validated by quantitative real-time PCR (qRT-PCR) in 15 controls and 30 HF patients. The diagnostic value of three successfully validated miRNAs for heart failure was assessed using receiver operating characteristic curve (ROC) analysis. Finally, to explore the expression levels of the three successfully validated miRNAs in HF hearts, thoracic aortic constriction (TAC) mice models were constructed and their expression in mice hearts was detected by qRT-PCR. RESULTS: Sixty-three differentially expressed miRNAs were identified by high-throughput sequencing. Of these 63 miRNAs, most were located on chromosome 14, and the OMIM database showed that 14 miRNAs were associated with HF. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that the target genes were mostly involved in ion or protein binding, the calcium signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, inositol phosphate metabolism, autophagy, and focal adhesion. Of the four selected miRNAs, hsa-miR-378d, hsa-miR-486-5p and hsa-miR-210-3p were successfully validated in the validation cohort and hsa-miR-210-3p had the highest diagnostic value for HF. Meanwhile, miR-210-3p was found to be significantly upregulated in the hearts of TAC mice. CONCLUSION: A reference set of potential miRNA biomarkers that may be involved in HF is constructed. Our study may provide new ideas for the diagnosis and treatment of HF.

The pattern of late gadolinium enhancement by cardiac MRI in fulminant myocarditis and its prognostic implication: a two-year follow-up study.

Background: Myocardial fibrosis, as quantified by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR), provides valuable prognostic information for patients with myocarditis. However, due to the low incidence rate of fulminant myocarditis (FM) and accordingly small sample size, the knowledge about the role of LGE to patients with FM is limited. Methods and results: A total of 44 adults with viral-FM receiving the Chinese treating regimen were included in this retrospective study. They were divided into the low LGE group and the high LGE group according to the ratio of LGE to left ventricular mass (LGE mass%). CMR exams and LGE were performed after hemodynamic assistance at discharge in all patients with FM. Routine echocardiography parameters and global longitudinal strain (GLS) at discharge and at 2-year follow-up were obtained and then compared. Both left ventricular ejection fraction (LVEF) and GLS showed no significant difference in both groups at discharge, whereas significant differences were observed at 2-year follow-up between two groups. Moreover, there were significant improvements of LVEF and GLS in the low LGE group, but not in the high LGE group during the 2-year period. Furthermore, LGE mass% was negatively correlated with GLS and LVEF. Conclusions: There were two distinct forms of LGE presentation in patients with FM. Moreover, the cardiac function of patients with low LGE was significantly better than those with high LGE at 2-year follow-up. LGE mass% at discharge provided significant prognosis information about cardiac function of patients with FM.

Left ventricular function changes and echocardiographic predictors in adult survivors of fulminant myocarditis treated with the Chinese protocol.

Disagreement exists regarding the long-term prognosis and recovery of left ventricular (LV) function in patients with fulminant myocarditis (FM). This study reported the outcome and LV ejection fraction (EF) changes in FM treated with Chinese protocol, and assessed whether global longitudinal strain (GLS) by two-dimensional speckle tracking echocardiography (2-D STE) could provide additional information. This retrospective study included 46 FM adult patients who applied timely circulatory support and immunomodulatory therapy with adequate doses of both glucocorticoids and immunoglobulins as core approaches and survived after acute phase. They all presented with acute onset of cardiac symptoms < 2 weeks. LV end-diastolic dimensions, LVEF and GLS at discharge and 2-year were obtained and compared. We then performed linear regression and ROC analysis to determine independent factors to predict normalization of GLS at 2-year. At 2 years, the survival was 100% in our cohort. And the GLS improved modestly (15.40 ± 3.89% vs 17.24 ± 2.89%, P = 0.002). At two years, a proportion of patients whose LV function remained abnormal, being 22% evaluated by EF (< 55%) and higher to 37% by GLS (< 17%). Moreover, GLS at discharge but not at presentation correlated with GLS at 2-year (r = 0.402, P = 0.007). The FM adult treated with Chinese protocol have good survival and modest improvement of LV function during 2-year.

Unusual presentation of systemic lupus erythematosus as hemophagocytic lymphohistiocytosis in a female patient: A case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disorder, often resulting in the immune-mediated injury of multiple organ systems, including primary HLH and secondary HLH (sHLH). Among them, sHLH results from infections, malignant, or autoimmune conditions, which have quite poor outcomes even with aggressive management and are more common in adults. CASE SUMMARY: We report a rare case of a 36-year-old female manifested with sHLH on background with systemic lupus erythematosus (SLE). During hospitalization, the patient was characterized by recurrent high-grade fever, petechiae and ecchymoses of abdominal skin, and pulmonary infection. Whole exon gene sequencing revealed decreased activity of natural killer cells. She received systematic treatment with Methylprednisolone, Etoposide, and anti-infective drugs. Intravenous immunoglobulin and plasmapheresis were applied when the condition was extremely acute and progressive. The patient recovered and did not present any relapse of the HLH for one year of follow-up. CONCLUSION: The case showed sHLH, thrombotic microvascular, and infection in the whole course of the disease, which was rarely reported by now. The treatment of the patient emphasizes that early recognition and treatment of sHLH in SLE patients was of utmost importance to improve the prognosis and survival rate of patients.

The effect of type 2 diabetes mellitus on multiple obstructive coronary artery disease.

BACKGROUND: Although type 2 diabetes mellitus (T2DM) individuals easily develop three-vessel disease (3VD) coronary artery disease (CAD), there is very little information available about their left ventricle (LV) functions. The purpose of this study is to evaluate the LV function using two-dimensional speckle tracking echocardiography (2-D STE) in T2DM patients with 3VD. METHODS: One hundred and three consecutive patients with confirmed 3VD CAD were enrolled and divided into two groups, while 53 patients with DM and 50 patients without. The control group was composed of 30 age- and sex-matched healthy individuals. All patients underwent 2-D STE and standard echocardiograms. The durations of DM and the level of HbA1c were also recorded. RESULT: Between the 3VD-DM and 3VD-non-DM groups, normal echocardiography did not reveal any appreciable differences. However, patients with 3VD-DM had significantly lower global longitudinal strain (GLS) than those with 3VD-non-DM (15.87 ± 2.51 vs.17.56 ± 2.72, p < .05) by 2-D STE strain measurement. Besides, patients whose duration of DM excess 5 years showed significant lower GLS than those with less than 5 years duration (14.25 ± 2.31 vs. 16.65 ± 1.96, p = .007). However, there was no difference in GLS between the 3VD-DM patients with HbA1c ≥ 7% and HbA1c < 7%. CONCLUSIONS: Compared to patients with 3VD alone, those with 3VD-DM have a lower cardiac function. In 3VD-DM patients, the duration of DM is a significant factor that contributes to cardiac function deterioration, whereas, the glucose control state has limited influence.

Support Life Club: A New Model Based on Social Media Group Chats and Social Activities That Can Improve Adherence and Clinical Outcomes in Patients Receiving Cardiac Rehabilitation.

Aim: To describe a new model, the Support Life Club (SLC), for participants of Phase II cardiac rehabilitation (CR) programs and to evaluate this model for adherence, completion rates, and clinical outcomes. Methods: This retrospective study involved 391 consecutive patients who participated in an outpatient CR program between September 2016 and May 2020. The intervention group (SLC) was comprised of 198 patients who participated in education, WeChat-based group activity as well as outdoor activities, while the control group (non-intervention) was comprised of 193 cases. All patients attended a 12-week supervised outpatient CR program (three sessions per week, each lasting 40min). The intervention and control groups were compared for completion rates, Cardiopulmonary Exercise Test (CPET) results, Six-minute Walk Test (6MWT) distances, and Patient Health Questionnaire-9 (PHQ-9) scores. Results: Patients in the intervention group attended at least 75% of the exercise training sessions more often than those in the control group (72.5% vs 40.41%, adjusted odds ratio (OR): 27.385; 95% CI: 10.2 to 73.6; P = 0.0000). Analysis of variance (2 × 2 ANOVA) revealed a significant group-by-time interaction in PHQ9 and 6MWT test results (p = 0.000). Conclusion: The addition of SLC to a cardiac rehabilitation program resulted in better outcomes for PHQ9 and 6MWT tests and may be a useful strategy to improve exercise adherence.

The Value of Cardiopulmonary Exercise Testing in Predicting the Severity of Coronary Artery Disease.

Background: There have been a limited number of quantitative studies on the relationship between coronary artery disease (CAD) and cardiorespiratory fitness (CRF), as measured by cardiopulmonary exercise testing (CPET). Thus, we aimed to investigate the association between CRF and the severity of coronary artery disease from the most comprehensive perspective possible, and to affirm the predictive value of CPET in the severity assessment of CAD. Methods: Our study included 280 patients with coronary angiography, who had undergone CPET in Tongji Hospital. The patients' CRF was measured through their peak oxygen uptake (VO2@peak), their oxygen uptake at the anaerobic threshold (VO2@AT) and through other parameters of CPET on a bicycle ergometer. The severity of the coronary artery disease was assessed in the following three layers: functionally significant lesions (quantitative flow ratio [QFR] ≤ 0.8), the number of stenotic coronary arteries (SCA, stenosis ≥ 50%) and the Gensini score. The correlation analyses were carried out between the CRF and the severity of the coronary artery disease. A ROC curve was plotted, and the AUC was calculated to distinguish the severe CAD and the non-severe CAD patients, as measured by the QFR, the number of SCA, and the Gensini score. Results: The VO2@AT and VO2@peak were inversely associated with the QFR. The VO2@AT, VO2@peak and VO2/kg@peak were associated with the number of SCA. Meanwhile, the VO2@AT, VO2/kg@AT, VO2@peak and VO2/kg@peak were associated with the Gensini score. An ROC analysis proved that a combination of traditional clinical risk factors and the VO2@peak/VO2prediction is valuable in predicting CAD severity. Conclusions: Our study demonstrated a strong and inverse association between CRF and the severity of CAD. A combination of traditional clinical risk factors and CRF is valuable in predicting CAD severity.

Soluble ST2 Is a Sensitive and Specific Biomarker for Fulminant Myocarditis.

Background The aim of the study was to identify biomarkers that can facilitate early diagnosis and treatment of fulminant myocarditis (FM) in order to reduce mortality. Methods and Results First, the expression profiles of circulating cytokines were determined in the plasma samples from 4 patients with FM and 4 controls using human cytokine arrays. The results showed that 39 cytokines from patients with FM were changed at admission. Among them, 8 cytokines returned to normal levels at discharge, including soluble ST2 (sST2), which showed the most marked dynamic changes from disease onset to resolution. Then, in a cohort of 76 patients with FM, 57 patients with acute hemodynamic dysfunction attributable to other causes, and 56 patients with non-FM, receiver operating characteristic curve analyses suggested that plasma sST2 level was able to differentiate FM from non-FM or other FM-unrelated acute heart failure more robustly N-terminal pro-B-type natriuretic peptide or cardiac troponin I. Moreover, longitudinal analysis of plasma sST2 was performed in 10 patients with FM during hospitalization and 16 patients with FM during follow-up. Finally, the diagnostic value was validated in an additional 26 patients with acute onset of unstable hemodynamics. The cutoff value of plasma sST2 for optimal diagnosis of FM was established at 58.39 ng/mL, where a sensitivity of 85.7% and specificity of 94.7% were achieved. Conclusions Elevated sST2 level was associated with mechanical stress or inflammation. Especially, sST2 might be used as a potential biomarker for the rapid diagnosis of FM, which was characterized by strong mechanical stretch stimulation and severe inflammatory response. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03268642.

Diagnostic Accuracy of Global Longitudinal Strain for Detecting Exercise Intolerance in Patients with Ischemic Heart Disease.

Objective: Global longitudinal strain (GLS) is a sensitive and reproducible predictive factor in patients with ischemic heart disease (IHD), although its correlation with exercise tolerance is unknown. We aimed to identify the correlation between global longitudinal strain (GLS) and cardiopulmonary exercise testing (CPX) parameters and assess the prognostic implications and accuracy of GLS in predicting exercise intolerance in populations with ischemic heart disease (IHD) using CPET criteria. Methods: Prospectively, 108 patients with IHD underwent CPX and 2D speckle-tracking echocardiography. Correlation between GLS and multiple CPX variables was assessed using Spearman's correlation analysis and univariate regression analysis. A receiver operating characteristic (ROC) curve analysis was performed on GLS to detect exercise intolerance. Results: GLS was correlated with peak oxygen uptake (peak VO2; r = −0.438, p = 0.000), %PPeak VO2 (−0.369, p = 0.000), peak metabolic equivalents (METs@peak; r = −0.438, p < 0.01), and the minute ventilation−carbon dioxide production (VE/VCO2) slope (r = 0.257, p < 0.01). Weak-to-moderate correlations were also identified for the respiratory exchange rate at the anaerobic threshold (RER@AT), end-tidal carbon dioxide at the anaerobic threshold (PETCO2@AT), oxygen consumption at the anaerobic threshold (VO2@AT), carbon dioxide production at the anaerobic threshold (VCO2@AT), and metabolic equivalents at the anaerobic threshold (METs@AT; p < 0.01). On multivariate analysis, the results showed that age, the BMI, and GLS are independent predictors for reduced exercise capacity in patients with IHD (p < 0.01). The area under the ROC curve value of GLS for identifying patients with a peak VO2 of <14 mL/kg/min was 0.73 (p = 0.000). Conclusion: As a sensitive echocardiographic assessment of patients with ischemic heart disease, global longitudinal strain is an independent predictor of reduced exercise capacity and has a sensitivity of 74.2% and a specificity of 66.7% to detect exercise intolerance.

Myocardial strain features by 2D-STE during the course of fulminant myocarditis: Correlation with characteristics by CMR and clinical implications.

ABSTRACT: Myocardial strain analysis by 2D speckle tracking echocardiography could determine the left ventricular function. Our purpose is to investigate the global longitudinal strain (GLS) changes during the course of fulminant myocarditis (FM) and evaluate their correlation with cardiac magnetic resonance (CMR).Patients with clinical diagnosis of FM from June 30, 2017 to June 30, 2019 were screened prospectively. 18 survived patients (mean age 34 ±â€Š18 years) who had two scans of transthoracic echocardiography and underwent CMR were included.All patients had severely impaired left ventricular ejection fraction and GLS value at admission that improved significantly before discharge. The patients in the healed stage revealed elevated global native T1 and T2 relaxation time and extracellular volume fraction as well, which were 1408.3 ±â€Š88.3ms, 46.56 ±â€Š5.23ms, and 0.35 ±â€Š0.09, respectively. GLS from the second transthoracic echocardiography in the healed stage correlated significantly with global native T1 relaxation time (r =-0.574, P = .013) and with extracellular volume fraction (r = -0.582, P = .011), but not global native T2 relaxation time (r = -0.31, P = .211) and not with late gadolinium enhancement mass (r = 0.084, P = .743). In comparison, GLS at admission were not correlated with CMR parameters of fibrosis and oedema in the healed stage.GLS by 2D-STE may emerge as a new tool to monitor inflammatory myocardial injuries during the course of FM. FM in the acute healed stage has the presence of both chronic fibrosis and oedema which are correlated with GLS, but GLS at admission can't predict the early recovery of myocardial inflammation.

Management perspectives from the 2019 Wuhan international workshop on fulminant myocarditis.

Fulminant myocarditis (FM) is a form of acute myocardial inflammation leading to rapid-onset hemodynamic instability due to cardiogenic shock or life-threatening arrhythmias. As highlighted by recent registries, FM is associated with high rates of death and heart transplantation, regardless of the underlying histology. Because of a paucity of evidence-based management strategies exists for this disease, an International workshop on FM was held in Wuhan, China, in October 2019, in order to share knowledge on the disease and identify areas of consensus. The present report highlights both agreements and controversies in FM management across the world, focusing the attention on areas of opportunity, FM definition, the use of endomyocardial biopsy and viral identification on heart specimens, treatment algorithms including immunosuppression and the timing of circulatory support escalation. This report incorporates the most recent recommendations from national and international professional societies. Main areas of interest and aims of future prospective observational registries and randomized controlled trials were finally identified and suggested.

Circulating miR-4763-3p Is a Novel Potential Biomarker Candidate for Human Adult Fulminant Myocarditis.

Circulating microRNAs (miRNAs) are potential biomarkers in various diseases. However, whether they could serve as biomarkers for human adult fulminant myocarditis (FM) is unknown. Circulating miRNA expression profiles were detected by microarray analysis and validated by quantitative real-time PCR arrays. Meanwhile, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to determine the critical roles of these circulating miRNAs in FM. Moreover, correlation analysis was employed between miRNAs and the parameters of cardiac functions in FM. Finally, the sensitivity and specificity of circulating long non-coding RNA (lncRNA) expression in FM diagnosis were evaluated using receiver operating characteristic curve analysis. Both microarray and quantitative real-time PCR analysis showed that the expression of miR-4763-3p and miR-4281 were upregulated in the plasma of FM at the onset, and their levels were restored as the clinical symptom recovered. The predicted target genes of miR-4763-3p and miR-4281 are involved in several pathways, mainly inflammatory and cardiac injury response. Moreover, the miRNAs enrichment was negatively correlated with the severity of FM. In addition, the expression levels of circulating miR-4763-3p were unchanged in myocardial infarction (MI) patients but showed high sensitivity and specificity for FM diagnosis. This study provides a global profile of circulating miRNAs in patients with FM, among which miR-4763-3p could serve as a potential biomarker.

Key Role of CD151-integrin Complex in Lung Cancer Metastasis and Mechanisms Involved.

Tetraspanin CD151 was found to be upregulated in malignant cell types and has been identified as a tumor metastasis promoter. In this study, we aimed to examine the role of the CD151-integrin complex in lung cancer metastasis and the underlying mechanisms. CD151 QRD194-196 →AAA194-196 mutant was generated and used to transfect A549 human lung adenocarcinoma cells. We found that there was no significant difference in CD151 protein expression between CD151 and CD151-AAA mutant groups. In vitro, CD151-AAA mutant delivery abrogated the migration and invasion of A549 cells, which was promoted by CD151 gene transfer. Furthermore, CD151-AAA delivery failed to activate FAK and p130Cas signaling pathways. Western blot and immunohistochemical staining showed strong CD151 expression in lung cancerous tissues but not in adjacent normal tissues. Increased level of CD151 protein was observed in 20 of the patients and the positive rate of CD151 protein in specimens was 62.5% (20/32). In addition, CD151 was co-localized with α3 integrin at the cell-cell contact site in carcinoma tissues. These results suggested that the disruption of the CD151-α3 integrin complex may impair the metastasis-promoting effects and signaling events induced by CD151 in lung cancer. Our findings identified a key role for CD151-α3 integrin complex as a promoter in the lung cancer.

Temporal echocardiography findings in patients with fulminant myocarditis: beyond ejection fraction decline.

The features of myocardial strains from speckle-tracking echocardiography (STE) have not been well defined in fulminant myocarditis (FM) patients. In this study, changes in the left ventricular ejection fraction (LVEF) and global and layer-specific myocardial strains over time were monitored. We aimed to determine the echocardiographic patterns of FM and ascertain their significance in FM treatment. Twenty patients who were clinically diagnosed with FM and received mechanical life support were prospectively enrolled. Conventional echocardiographic measurements were obtained, and serial strain echocardiography was performed from admission to hospital discharge until LVEF recovery (> 50%). Global/regional peak systolic longitudinal strains (GLS/RLS) and layer-specific longitudinal strains were quantified, and their changes with time were monitored in 14 FM patients. All patients had severely impaired cardiac function. Steep improvement in LVEF and GLS were observed within 6 days. Layer-specific strain analysis showed that reduction at admission or recovery at discharge in the endocardium and epicardium strains were equal. In conclusion, FM patients who received mechanical circulatory supports exhibited steep improvement in ventricular function within 6 days. The patchy and diffused distribution pattern of reduced RLS and equally and severely impaired strain in the endocardium and epicardium are valuable features in the diagnosis of FM.

Myocardial Deformation Pattern Differs between Ischemic and Non-ischemic Dilated Cardiomyopathy: The Diagnostic Value of Longitudinal Strains.

Both ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM) are characterized by left ventricular (LV) dysfunction and dilation. Differentiation between ICM and NICM using non-invasive image modalities is a clinical challenge. This study compared the myocardial deformation patterns of ICM and NICM using 2-D speckle tracking echocardiography (2-D STE) and sought to find parameters valuable in the diagnosis and management of dilated cardiomyopathy. The study population comprised 84 consecutive patients with LV end-diastolic dimension >55 mm and ejection fraction (EF) <45 %. Of these patients, 41 were diagnosed with ICM and 43 with NICM by coronary angiography. 2-D STE was performed in all patients. The LV dimension did not differ between ICM and NICM. Compared with patients with ICM, patients with NICM had lower EF (29.0% vs. 33.0%, p = 0.024), lower global longitudinal strain (-5.4 ± 2.6% vs. -7.0 ± 2.5%, p = 0.006) and lower global radial strain (7.5 ± 4.5% vs. 10.7 ± 4.7%, p = 0.019). In contrast, global longitudinal strains did not differ significantly. However, NICM patients had higher apical and lower basal longitudinal strains compared with those with ICM. The ratio of basal to sum of mid- and apical longitudinal strains could predict NICM with a sensitivity of 63.4% and specificity of 88.4% by receiver operating characteristic curve analysis (cutoff value: 0.47, area under the curve: 0.792). Moreover, the concomitant presence of non-significant coronary artery stenosis (>50% and <70%) had no significant influence on global longitudinal strain in NICM. In conclusion, LV dilation and systolic dysfunction, relative apical sparing and a basal worsening pattern of LV longitudinal strain by 2-D STE were observed in patients with NICM but not ICM. The ratio of basal to sum of mid- and apical longitudinal strains could help differentiate NICM from ICM.

Chinese society of cardiology expert consensus statement on the diagnosis and treatment of adult fulminant myocarditis.

Fulminant myocarditis is primarily caused by infection with any number of a variety of viruses. It arises quickly, progresses rapidly, and may lead to severe heart failure or circulatory failure presenting as rapid-onset hypotension and cardiogenic shock, with mortality rates as high as 50%-70%. Most importantly, there are no treatment options, guidelines or an expert consensus statement. Here, we provide the first expert consensus, the Chinese Society of Cardiology Expert Consensus Statement on the Diagnosis and Treatment of Fulminant Myocarditis, based on data from our recent clinical trial (NCT03268642). In this statement, we describe the clinical features and diagnostic criteria of fulminant myocarditis, and importantly, for the first time, we describe a new treatment regimen termed life support-based comprehensive treatment regimen. The core content of this treatment regimen includes (i) mechanical life support (applications of mechanical respirators and circulatory support systems, including intraaortic balloon pump and extracorporeal membrane oxygenation, (ii) immunological modulation by using sufficient doses of glucocorticoid, immunoglobulin and (iii) antiviral reagents using neuraminidase inhibitor. The proper application of this treatment regimen may and has helped to save the lives of many patients with fulminant myocarditis.