Prognosis and subtype analysis of left ventricular noncompaction in adults: A retrospective multicenter study.

BACKGROUND: Left ventricular noncompaction (LVNC) is a heterogeneous myocardial disorder with an uncertain prognosis. There was a lack of studies on LVNC subtypes at present. This study sought to identify the prognosis of the overall population of LVNC and to describe the distribution of different subtypes and compare their prognosis. HYPOTHESIS: Patients with different subtypes of LVNC may have different prognoses. METHODS: Patients who fulfilled the Jenni criteria and/or Petersen criteria were included. Major adverse cardiovascular events (MACE) were defined as a combination of heart failure (HF) hospitalization and all-cause mortality. RESULTS: A total of 200 patients from four hospitals were included. The mean age at diagnosis was 48.2 years, and 61.5% of the patients were male. Left ventricular ejection fraction (LVEF) < 50% was present in 54% of the patients. Over a mean retrospective time period of 22.2 months, 47 (23.5%) patients experienced MACE. Age (hazard ratio [HR] 1.03; 95% confidence interval [CI] 1.01-1.06; p = .004), LVEF < 50% (HR 2.32; 95% CI 1.09-4.91; p = .028) and ventricular tachycardia/ventricular fibrillation (HR 2.17; 95% CI 1.08-4.37; p = .03) were significantly associated with the risk of MACE. The most common subtype was dilated LVNC (51.3%), followed by benign LVNC (21.3%) and LVNC with arrhythmias (10.5%). Patients with dilated LVNC had significantly increased cumulative incidence of MACE, HF hospitalization, and all-cause mortality (p < .05). CONCLUSIONS: Age, LVEF < 50%, and ventricular tachycardia/ventricular fibrillation were independent risk factors for prognosis of LVNC. The most common subtype was dilated LVNC, which had a worse prognosis.

The burden of cardiovascular diseases attributable to metabolic risk factors and its change from 1990 to 2019: a systematic analysis and prediction.

Background: Metabolic disorders are the most important risk factors for cardiovascular diseases (CVDs). The purpose of this study was to systematically analyze and summarize the most recent data by age, sex, region, and time, and to forecast the future burden of diseases. Methods: Data on the burden of CVDs associated with metabolic risk factors were obtained from the Global Burden of Disease (GBD) Study 2019; and then the burden of disease was assessed using the numbers and age-standardized rates (ASR) of deaths, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) and analyzed for temporal changes, differences in age, region, sex, and socioeconomic aspects; finally, the burden of disease was predicted using an autoregressive integrated moving average (ARIMA) model. Results: From 1990 to 2019, the numbers of deaths, DALYs, YLDs, and YLLs attributed to metabolic risk factors increased by 59.3%, 51.0%, 104.6%, and 47.8%, respectively. The ASR decreased significantly. The burden of metabolic risk factor-associated CVDs was closely related to socioeconomic position and there were major geographical variations; additionally, men had a significantly greater disease burden than women, and the peak shifted later based on the age group. We predicted that the numbers of deaths and DALYs would reach 16.5 million and 324.8 million, respectively, by 2029. Conclusions: The global burden of CVDs associated with metabolic risk factors is considerable and still rising, and more effort is needed to intervene in metabolic disorders.

Left ventricular non-compaction cardiomyopathy associated with the PRKAG2 mutation.

Left ventricular non-compaction cardiomyopathy (LVNC) is one of the most common inherited cardiovascular diseases. The genetic backgrounds of most LVNC patients are not fully understood. We collected clinical data, family histories, and blood samples and performed genetic analysis using next-generation sequencing (NGS) from a Chinese family of 15 subjects. Clinically LVNC affected subjects showed marked cardiac phenotype heterogeneity. We found that these subjects with LVNC carried a missense heterozygous genetic mutation c.905G>A (p.R302Q) in γ2 subunit of AMP-activated protein kinase (PRKAG2) gene through NGS. Individuals without this mutation showed no symptoms or cardiac structural abnormalities related to LVNC. One subject was the victim of sudden cardiac death. To sum up, PRKAG2 mutation c.905G>A (p.R302Q) caused familial LVNC. Our results described a potentially pathogenic mutation associated with LVNC, which may further extend the spectrum of LVNC phenotypes related to PRKAG2 gene mutations.

Uric Acid Predicts Recovery of Left Ventricular Function and Adverse Events in Heart Failure With Reduced Ejection Fraction: Potential Mechanistic Insight From Network Analyses.

Background and Aims: Heart failure with reduced ejection fraction (HFrEF) still carries a high risk for a sustained decrease in left ventricular ejection fraction (LVEF) even with the optimal medical therapy. Currently, there is no effective tool to stratify these patients according to their recovery potential. We tested the hypothesis that uric acid (UA) could predict recovery of LVEF and prognosis of HFrEF patients and attempted to explore mechanistic relationship between hyperuricemia and HFrEF. Methods: HFrEF patients with hyperuricemia were selected from the National Inpatient Sample (NIS) 2016-2018 database and our Xianyang prospective cohort study. Demographics, cardiac risk factors, and cardiovascular events were identified. Network-based analysis was utilized to examine the relationship between recovery of LVEF and hyperuricemia, and we further elucidated the underlying mechanisms for the impact of hyperuricemia on HFrEF. Results: After adjusting confounding factors by propensity score matching, hyperuricemia was a determinant of HFrEF [OR 1.247 (1.172-1.328); P < 0.001] of NIS dataset. In Xianyang prospective cohort study, hyperuricemia is a significant and independent risk factor for all-cause death (adjusted HR 2.387, 95% CI 1.141-4.993; P = 0.021), heart failure readmission (adjusted HR 1.848, 95% CI 1.048-3.259; P = 0.034), and composite events (adjusted HR 1.706, 95% CI 1.001-2.906; P = 0.049) in HFrEF patients. UA value at baseline was negatively correlated to LVEF of follow-ups (r = -0.19; P = 0.046). Cutoff UA value of 312.5 µmmol/L at baseline can work as a predictor of LVEF recovery during follow-up, with the sensitivity of 66.7%, the specificity of 35.1%, and the accuracy of 0.668 (95% CI, 0.561-0.775; P = 0.006). Moreover, gene overlap analysis and network proximity analysis demonstrated a strong correlation between HFrEF and Hyperuricemia. Conclusion: Lower baseline UA value predicted the LVEF recovery and less long-term adverse events in HFrEF patients. Our results provide new insights into underlying mechanistic relationship between hyperuricemia and HFrEF.

The burden of alcoholic cardiomyopathy in China and different regions around the world.

Background: Alcoholic cardiomyopathy (ACM) remains a significant public health issue with a growing global burden. The burden of ACM in China and different regions remains poorly understood. Methods: Data on ACM deaths, disability-adjusted life years (DALYs), the corresponding global age-standardized death rate (ASDR), age-standardized DALY rate and estimated annual percentage change (EAPC) were analysed based on age, sex, socio-demographic index (SDI) quintiles, different regions and in China from the Global Burden of Disease (GBD) study 2019. Results: Globally, the death rate and DALYs due to ACM were 71 723 and 2 441 108 in 2019, 33.06% and 38.79% increase from 1990, respectively. The corresponding ASDR and age-standardized DALY rate decreased with EAPC of -1.52 (95% uncertainty interval (UI) = -2.39, -0.65) and -1.12 (95% UI = -2.14, -0.10). The high-middle SDI regions, especially Eastern Europe, showed the highest number of ACM-related deaths and DALYs. The ACM-related deaths and DALYs were 2545 and 87823 in China in 2019, 171.03% and 147.17% increase from 1990, respectively. Unlike the world level, ASDR and age-standardized DALY rate also increased in China. The ACM burden is higher in men, and people with 50 to 69 years old accounted for the most. Conclusions: ACM burden in China and across the world increased substantially from 1990 to 2019. The greatest burden was borne by the high-middle SDI regions, especially by men aged 50-69 years old. Geographically and gender-age tailored strategies were needed to prevent ACM.

Circular RNA circ_0001006 aggravates cardiac hypertrophy via miR-214-3p/PAK6 axis.

AIM: Circular RNAs (circRNAs) control gene expression in a series of physiological and pathological processes, but their role in heart disease is unknown. This research illustrates the role and potential mechanism of circRNA in cardiac hypertrophy. METHODS AND RESULTS: In this report, we found that circular RNA hsa_circ_0001006 (circ_0001006) was upregulated in cardiac hypertrophy mice and cardiomyocytes treated with angiotensin II (Ang II). Next, we noticed that gain of function circ_0001006 could induce cardiomyocyte hypertrophy; oppositely, knockdown of circ_0001006 remitted Ang II-induced cardiomyocyte hypertrophy. Biotin-coupled miRNA and RNA-pull down assays showed that miR-214-3p could bind with circ_0001006 and gain the function of miR-214-3p abrogated the pro-hypertrophy effect of circ_0001006. Furthermore, Further, dual-luciferase reporter assay showed that miR-214-3p could interact with 3'UTRs of the PAK6 gene, and circRNA_0001006 could block the above interactions. Additionally, PAK6 expression is inhibited by miR-214-3p mimic in cardiomyocytes but enhanced by over-expression of circRNA_000203 in vitro. CONCLUSIONS: Our data demonstrated that circRNA_0001006 exacerbates cardiac hypertrophy via suppressing miR-214-3p leading to enhanced PAK6 levels.

The LDL/HDL ratio predicts long-term risk of coronary revascularization in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention: a cohort study.

Clinical indicators do not adequately predict the long-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) following percutaneous coronary intervention (PCI). The low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio is expected to be a reliable predictor of the long-term prognosis of these patients. This study aimed to explore the correlation between the LDL/HDL ratio and long-term prognosis in STEMI patients undergoing PCI. Patients with confirmed STEMI who underwent PCI in 7 hospitals in China from January 2009 to December 2011 were enrolled. Information about clinical endpoints, including all-cause death and major adverse cardiovascular events, was collected. Overall, 915 patients were included for analysis, the average follow-up time was 112.2 months. According to the LDL/HDL ratio, the patients were divided into 3 groups using the three-quantile method: low (LDL/HDL≤1.963), medium (1.963

Cardiovascular disease burden attributable to dietary risk factors from 1990 to 2019: A systematic analysis of the Global Burden of Disease study.

BACKGROUND AND AIMS: Dietary risks have always been a major risk factor for cardiovascular diseases (CVDs), especially in young people. This article aimed to provide an updated and comprehensive view of the spatial, temporal and sexual heterogeneity in diet-attributable CVD burdens from 1990 to 2019. METHODS AND RESULTS: Data on diet-attributable CVD burdens were extracted from the Global Burden of Disease (GBD) Study 2019. Numbers and age-standardized rates (ASRs) of deaths, disability-adjusted life years (DALYs) and corresponding estimated annual percentage change (EAPC) were determined. Globally, the number of diet-attributable CVD deaths and DALYs in 2019 were 6.9 million and 153.2 million, marking 43.8% and 34.3% increases since 1990, respectively. However, ASRs of death and DALYs have declined over time. The regions with the highest ASRs of diet-related CVD deaths and DALYs were in Central Asia, whereas the lowest ASRs of CVD deaths and DALYs were observed in the high-income Asia Pacific region. Globally, men suffered higher death and DALY burdens than women. Ischemic heart disease and stroke were the leading causes of CVD deaths and DALYs, globally. Regarding the specific diet group, diets low in whole grains, high in sodium, low in fruits, low in nuts and seeds, low in vegetables and low in seafood omega-3 fatty acids contributed to CVD deaths and DALYs the most. Dietary risks accounted for a higher proportion in people aged less than 65 years old. CONCLUSIONS: Diet-attributable CVDs threaten public health, particularly in low SDI countries and younger generations. As diet-related CVDs are nation-specific, the prioritization of public health interventions should be evidence-based.

LncRNA SNHG16 accelerates atherosclerosis and promotes ox-LDL-induced VSMC growth via the miRNA-22-3p/HMGB2 axis.

Long non-coding RNAs (LncRNAs) are essential regulators in the occurrence and development of AS. Here we aim to explore the underlying molecular mechanism of LncRNA SNHG16 in regulating ox-LDL-induced VSMC proliferation, migration and invasion. After constructing AS in vivo and in vitro models, the expressions of SNHG16, miR-22-3p, HMBG2, proliferation- and metastasis-related proteins were determined by qRT-PCR and Western blot assays. Detection of serological lipids, H&E and Masson staining analysis were conducted to evaluate the AS injury in mice. The effects of ox-LDL treatment on VSMCs were examined by CCK-8, wound scratch and Transwell Chamber assays. The targeted relationship was measured by luciferase reporter and RIP assays. The results showed that SNHG16 and high-mobility group box 2 (HMGB2) expressions were increased while miRNA-22-3p expression was decreased in AS mice and ox-LDL-stimulated VSMCs. Functionally, sh-SNHG16 restrained ox-LDL-induced VSMC growth and migration. SNHG16 suppressed miRNA-22-3p expression by direct binding. Furthermore, in ox-LDL-treated VSMCs, miRNA-22-3p mimic prevented proliferation, migration, and invasion. Further explorations showed that HMGB2 was a target of miRNA-22-3p, SNHG16 upregulated HMGB2 levels by acting as a competing endogenous RNA (ceRNA) of miRNA-22-3p. More importantly, sh-HMGB2 partially reversed the effects of sh-SNHG16 together with miR-22-2p inhibitor on ox-LDL-induced VSMC proliferation, migration and invasion. Collectively, SNHG16 accelerated atherosclerotic plaque (AP) formation and enhanced ox-LDL-activated VSMCs proliferation and migration by miRNA-22-3p/HMGB2 axis.

Histone deacetylase 3 suppresses the expression of SHP-1 via deacetylation of DNMT1 to promote heart failure.

AIMS: Heart failure (HF) is a progressive disease with recurrent hospitalizations and high mortality. However, the mechanisms underlying HF remain unclear. The present study aimed to explore the regulatory mechanism of histone deacetylase 3 (HDAC3) and DNA methyltransferase 1 (DNMT1)/Src homology domain 2-containing tyrosine phosphatase-1 (SHP-1) axis in HF. METHODS: The HF rat models and hypertrophy cell models were established. The characteristic parameters of the heart were detected by echocardiography. A multichannel physiological signal acquisition system was used to detect the hemodynamic parameters. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of HDAC3, DNMT1, and SHP-1 mRNAs, while Western blot was applied to analyze the expression of proteins. Masson staining was used to analyze the degree of collagen fiber infiltration. TdT-mediated DUTP nick end labeling (TUNEL) staining was performed to analyze the apoptosis of myocardial tissue cells. Co-immunoprecipitation (co-IP) was conducted to study the interaction between HDAC3 and DNMT1. Flow cytometry was used to analyze the apoptosis. KEY FINDINGS: HDAC3 and DNMT1 were highly expressed in HF rat and hypertrophy cell models. HDAC3 modified DNMT1 through deacetylation to inhibit ubiquitination-mediated degradation, which promoted the expression of DNMT1. DNMT1 inhibited SHP-1 expression via methylation in the promoter region. In summary, HDAC3 modified DNMT1 by deacetylation to suppress SHP-1 expression, which in turn led to the development of cardiomyocyte hypertrophy-induced HF. SIGNIFICANCE: This study provided potential therapeutic targets for HF treatment.

The LDL/HDL ratio predicts long-term risk of coronary revascularization in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention: a cohort study

Clinical indicators do not adequately predict the long-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) following percutaneous coronary intervention (PCI). The low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio is expected to be a reliable predictor of the long-term prognosis of these patients. This study aimed to explore the correlation between the LDL/HDL ratio and long-term prognosis in STEMI patients undergoing PCI. Patients with confirmed STEMI who underwent PCI in 7 hospitals in China from January 2009 to December 2011 were enrolled. Information about clinical endpoints, including all-cause death and major adverse cardiovascular events, was collected. Overall, 915 patients were included for analysis, the average follow-up time was 112.2 months. According to the LDL/HDL ratio, the patients were divided into 3 groups using the three-quantile method: low (LDL/HDL≤1.963), medium (1.963<LDL/HDL<2.595), and high (LDL/HDL≥2.595) LDL/HDL groups. The rate of coronary revascularization was higher in the high LDL/HDL group (28.52%) than in the low (17.38%, P=0.001) and medium (19.34%, P=0.010) LDL/HDL groups. The hazard ratio of coronary revascularization was significantly higher in the high LDL/HDL group than in the low (P=0.007) and medium (P=0.004) LDL/HDL groups. Increased LDL/HDL ratio was an independent risk factor for long-term coronary revascularization in STEMI patients undergoing PCI (HR=1.231, 95%CI: 1.023-1.482, P=0.028). These findings suggest that an increased LDL/HDL ratio was an independent risk factor for long-term coronary revascularization in STEMI patients undergoing PCI. The risk of coronary revascularization was significantly increased in patients with LDL/HDL≥2.595.

Animal models used in the research of nanoparticles for cardiovascular diseases.

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity worldwide. Tremendous progress has been made in the prevention and treatment of CVD; however, there are still lots of limitations and new technology is needed. Nanoparticles have been studied recently for CVD due to their nanoscale size and unique properties, and hold a potential to be a novel therapy for the treatment. To test the safety and effectiveness of drug-loaded nanoparticles for CVD prior to human studies, animal disease models are unavoidably needed. This review summarized the animal models used in the research of nanoparticles for CVD and provided a generic picture of current use of CVD animal models according to the different types of diseases which should be prioritized when considering the application of nanoparticles in treating CVD. This review would be useful resources not only for life science researchers and clinicians but also for those from chemistry and materials sciences background who may not have a systematic knowledge about CVD animal models.

Global burden of cardiovascular diseases attributable to hypertension in young adults from 1990 to 2019.

BACKGROUND: Hypertension grows into a serious public health problem among young adults, linking to a set of life-threatening cardiovascular diseases (CVDs). Young adults are not well represented in current knowledge about the CVDs burden attributable to hypertension. METHODS: In this analysis of data from the GBD (Global Burden of Disease) study 2019, we focus on young adults and provide the first comprehensive and comparative assessment of the hypertension attributable CVDs burden, in terms of its mortality and years of living with disability (YLD) from 1990 to 2019, stratified by location, sex, and development status. RESULTS: Globally in 2019, the death and YLD numbers caused by hypertension-related CVDs were 640 239 and 2 717 474 in young adults, marking a 43.0 and 86.6% increase from 1990, respectively. The corresponding mortality rate dropped by 10.5%, whereas the YLD rate increased by 16.8% during the same period. V-shaped association between CVDs burden and social development status was observed. The largest burden and the most pronounced increase were borne by middle-income countries, while high-income countries had the lowest death/YLD rate with a quicker annual decline. Men largely outpaced women in hypertension attributable CVDs mortality. Ischemic heart disease and stroke were the leading cause for death and YLD burden, correspondingly. CONCLUSIONS: Hypertension attributable CVDs burden in young adults has greatly increased from 1990 to 2019, with considerably spatiotemporal and sexual heterogeneity. The largest burden was borne by middle-income countries, especially by men. Establishment of geographically and sexually tailored strategies were needed to prevent hypertension-related CVDs in young adults.

Global, Regional, and National Burden of Myocarditis From 1990 to 2017: A Systematic Analysis Based on the Global Burden of Disease Study 2017.

Objective: The global trends in myocarditis burden over the past two decades remain poorly understood and might be increasing during the coronavirus disease 2019 (COVID-19) worldwide pandemic. This study aimed to provide comprehensive estimates of the incidence, mortality, and disability-adjusted life years (DALYs) for myocarditis globally from 1990 to 2017. Methods: Data regarding the incidence, mortality, DALY, and estimated annual percentage change (EAPC) between 1990 and 2017 for myocarditis worldwide were collected and calculated from the 2017 Global Burden of Disease study. We additionally calculated the myocarditis burden distribution based on the Socio-Demographic Index (SDI) quintile and Human Development Index (HDI). Results: The incidence cases of myocarditis in 2017 was 3,071,000, with a 59.6% increase from 1990, while the age-standardized incidence rate (ASIR) was slightly decreased. The number of deaths due to myocarditis increased gradually from 27,120 in 1990 to 46,490 in 2017. The middle SDI quintile showed the highest number of myocarditis-related deaths. On the contrary, the global age-standardized death rate (ASDR) decreased with an overall EAPC of -1.4 [95% uncertainty interval (UI) = -1.8 to -1.0]. Similar to ASDR, the global age-standardized DALY rate also declined, with an EAPC of -1.50 (95% UI = -2.30 to -0.8) from 1990 to 2017. However, there was a 12.1% increase in the number of DALYs in the past 28 years; the middle SDI and low-middle SDI quintiles contributed the most to the DALY number in 2017. We also observed significant positive correlations between the EPAC of age-standardized rate and HDI for both death and DALY in 2017. Conclusions: Globally, the ASIR, ASDR, and age-standardized DALY rate of myocarditis decreased slightly from 1990 to 2017. The middle SDI quintile had the highest level of ASIR, ASDR, and age-standardized DALY rate, indicating that targeted control should be developed to reduce the myocarditis burden especially based on the regional socioeconomic status. Our findings also provide a platform for further investigation into the myocarditis burden in the era of COVID-19.

Global Burden of Aortic Aneurysm and Attributable Risk Factors from 1990 to 2017.

Background: To date, our understanding of the global aortic aneurysm (AA) burden distribution is very limited. Objective: To assess a full view of global AA burden distribution and attributable risk factors from 1990 to 2017. Methods: We extracted data of AA deaths, disability-adjusted life years (DALYs), and their corresponding age-standardized rates (ASRs), in general and by age/sex from the 2017 Global Burden of Disease (GBD) study. The current AA burden distribution in 2017 and its changing trend from 1990 to 2017 were separately showed. The spatial divergence was discussed from four levels: global, five social-demographic index regions, 21 GBD regions, and 195 countries and territories. We also estimated the risk factors attributable to AA related deaths. Results: Globally, the AA deaths were 167,249 with an age-standardized death rate (ASDR) of 2.19/100,000 persons in 2017, among which the elderly and the males accounted for the majority. Although reductions in ASRs were observed in developed areas, AA remained an important health issue in those relatively underdeveloped areas and might be much more important in the near future. AA may increasingly affect the elderly and the female population. Similar patterns of AA DALYs burden were noted during the study period. AA burden attributable to high blood pressure and smoking decreased globally and there were many heterogeneities in their distribution. Discussion: AA maintained an incremental public health issue worldwide. The change pattern of AA burden was heterogeneous across locations, ages, and sexes and it is paramount to improve resource allocation for more effective and targeted prevention strategies. Also, prevention of tobacco consumption and blood pressure control should be emphasized.

Prognostic value of estimated plasma volume in patients with chronic systolic heart failure.

Assessing congestion is challenging but important to patients with chronic heart failure (CHF). However, there are limited data regarding the association between estimated plasma volume status (ePVS) determined using hemoglobin/hematocrit data and outcomes in patients with stable CHF. We prospectively analyzed 231 patients; the median follow-up period was 35.6 months. We calculated ePVS at admission using the Duarte and Strauss formula, derived from hemoglobin and hematocrit ratios and divided patients into three groups. The primary outcome was a composite of all-cause mortality or heart failure rehospitalization. Among 274 patients (61.98 years of age, 2.3% male), the mean ePVS was 3.98±0.90 dL/g. The third ePVS tertile had a higher proportion of primary outcome (71.4%) than the first or second tertile (48.1% and 59.7%, respectively; p=0.013). On multivariable Cox analysis, after adjusting for potential confounders, higher ePVS remained significantly associated with increased rate of primary outcome (adjusted HR 1.567, 95% CI 1.267 to 1.936; p<0.001). Kaplan-Meier survival analyses showed that the occurrence of primary outcome, all-cause mortality and rehospitalization increased progressively from first to third tertiles (p=0.006, 0.014 and 0.001; respectively). In receiver operating characteristic analysis, the area under the curve of ePVS for primary outcome was 0.645. ePVS determined using hemoglobin and hematocrit was independently associated with clinical outcomes for patients with stable CHF. Our study thus further strengthens the evidence that ePVS has important prognostic value in patients with stable CHF. Trial registration number ChiCTR-ONC-14004463.

The Diagnostic and Prognostic Value of Plasma Galectin 3 in HFrEF Related to the Etiology of Heart Failure.

Aim: The aim of present study is to evaluate the diagnostic and prognostic value of plasma galectin 3 (Gal-3) for HF originating from different causes. Methods: We investigated the plasma levels and expression of Gal-3 in cardiac tissues in two transgenic (TG) strains of mice with cardiomyocyte-restricted overexpression of either ß2- adrenergic receptor (ß2- AR TG) or Mammalian sterile 20-like kinase 1 (Mst1-TG) in the present study. Additionally, 166 patients suffering from heart failure with reduced ejection fraction (HFrEF) in two hospitals within the Shaanxi province were examined in this study. All these patients were treated according to the Chinese HF guidelines of 2014; subsequently, they were followed up for 50 months, and we analyzed the prediction value of baseline Gal-3 to endpoints in these patients. Results: Gal-3 was localized in the cytoplasm and nucleus of cardiomyocytes, often formed aggregates in Mst1-TG mice. Extracellular Gal-3 staining was uncommon in Mst1-TG hearts. However, in ß2-AR TG mice, although Gal-3 was also expressed in myocardial cells, it was more highly expressed in interstitial cells (e.g., fibroblasts and macrophages). Plasma Gal-3 was comparable between nTG and Mst1-TG mice. However, plasma Gal-3 was higher in ß2-AR TG mice than in nTG mice. In the cohort of HFrEF patients, the median plasma Gal-3 concentration was 158.42 pg/mL. All participants were divided into two groups according to Gal-3 levels. Patients with Gal-3 concentrations above the median were older, and had lower plasma hemoglobin, but higher plasma creatinine, tissue inhibitor of metalloproteinases 1 (TIMP-1), left ventricular end systolic diameter (LVESD), left ventricular end-systolic volumes (LVESV) and end-diastolic, as well as left ventricular end-diastolic volumes (LVEDV). Spearman correlation analysis revealed that Gal-3 was positively correlated with TIMP-1 (r = 0.396, P < 0.001), LVESV (r = 0.181, P = 0.020) and LVEDV (r = 0.190, P = 0.015). The 50-month clinical follow-up revealed 43 deaths, 97 unplanned re-hospitalizations, and 111 composite endpoint events. Cox analysis demonstrated that although Gal-3 did not provide any prognostic value in either total-HF subjects or coronary-heart-disease (CHD) patients, it did provide prognostic value in non-CHD patients. Conclusion: Although plasma Gal-3 is associated with TIMP-1 and echocardiographic parameters, the diagnostic and prognostic value of Gal-3 in HFrEF is determined by the etiology of HF.

Correction to: Cardiac rupture complicating acute myocardial infarction: the clinical features from an observational study and animal experiment.

An amendment to this paper has been published and can be accessed via the original article.

Cardiac rupture complicating acute myocardial infarction: the clinical features from an observational study and animal experiment.

BACKGROUND: Cardiac rupture (CR) is a fatal complication of ST-elevation myocardial infarction (STEMI) with its incidence markedly declined in the recent decades. However, clinical features of CR patients now and the effect of reperfusion therapy to CR remain unclear. We investigated the clinical features of CR in STEMI patients and the effect of reperfusion therapy to CR in mice. METHODS: Two studies were conducted. In clinical study, data of 1456 STEMI patients admitted to the First Hospital, Xi'an Jiaotong University during 2015.12. ~ 2018.12. were analyzed. In experimental study, 83 male C57BL/6 mice were operated to induce MI. Of them, 39 mice were permanent MI (group-1), and remaining mice received reperfusion after 1 h ischemia (21 mice, group-2) or 4 h ischemia (23 mice, group-3). All operated mice were monitored up to day-10. Animals were inspected three times daily for the incidence of death and autopsy was done for all mice found died to determine the cause of death. RESULTS: CR was diagnosed in 40 patients: free-wall rupture in 17, ventricular septal rupture in 20, and combined locations in 3 cases. CR presented in 19 patients at admission and diagnosed in another 21 patients during 1 ~ 14 days post-STEMI, giving an in-hospital incidence of 1.4%. The mortality of CR patients was high during hospitalization accounting for 39% of total in-hospital death. By multivariate logistic regression analysis, older age, peak CK-MB and peak hs-CRP were independent predictors of CR post-STEMI. In mice with non-reperfused MI, 17 animals (43.6%) died of CR that occurred during 3-6 days post-MI. In MI mice received early or delayed reperfusion, all mice survived to the end of experiment except one mouse died of acute heart failure. CONCLUSION: CR remains as a major cause of in-hospital death in STEMI patients. CR patients are characterized of being elderly, having larger infarct and more server inflammation. Experimentally, reperfusion post-MI prevented CR.

Exendin-4 reverses high glucose-induced endothelial progenitor cell dysfunction via SDF-1ß/CXCR7-AMPK/p38-MAPK/IL-6 axis.

AIM: Exendin-4, a glucagon-like peptide-1 (GLP-1) analog, has been used for treating diabetes mellitus (DM). However, its effects on improving the dysfunction of high glucose (HG)-induced endothelial progenitor cells (EPCs) remain unclear. The present study explored the effects of Exendin-4 on improving dysfunction of EPCs and the underlying mechanism. METHODS: EPCs were isolated from SD rats and identified by flow cytometry. Next, the EPCs were treated by HG and high or low concentration of Exendin-4, and cell viability, migration and tube formation were, respectively, examined by performing MTT assay, wound-healing assay and tube formation assay. Interleukin-6 (IL-6) secretion was measured by enzyme-linked immunosorbent assay (ELISA). The protein expressions of relative stromal-derived growth factor-1ß (SDF-1ß), C-X-C chemokine receptor type 7 (CXCR7), AMP-activated protein kinase (AMPK), p38 and expressions of CXCR7 and IL-6 in EPCs were measured by Western blot. The cell behaviors of EPCs treated by HG and Exendin-4 with or without silencing of CXCR7 and IL-6 were detected. RESULTS: Exendin-4 reversed the inhibitory effects of HG on viability, migration and tube formation of EPCs and on SDF-1ß/CXCR7-AMPK pathway in EPCs in a dose-dependent manner. Moreover, Exendin-4 promoted the effects of HG on IL-6 level in EPCs through the promotion of p38-MAPK phosphorylation and reduction of cleaved caspase-3 protein expressions in EPCs. However, silencing of CXCR7 and IL-6 reversed the effects of Exendin-4 on cell behaviors, inactivated SDF-1ß/CXCR7-AMPK pathway and increased cleaved caspase-3 expression in EPCs. CONCLUSIONS: Exendin-4 could ameliorate HG-induced EPC dysfunction through regulating the production of IL-6 via SDF-1ß/CXCR7-AMPK/p38-MAPK axis.