Anomalous origin of the coronary artery: prevalence and coronary artery disease in adults undergoing coronary tomographic angiography.

BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital coronary anomaly with the potential to cause adverse cardiac events. However, there is limited data on the association between AAOCA and coronary artery disease (CAD). Therefore, the aim of this study is to determine the prevalence and symptoms of patients with AAOCA, as well as investigate the correlation between AAOCA and CAD in a population referred for coronary computed tomographic angiography (CTA). METHODS AND RESULTS: All consecutive patients who underwent CTA from 2010 to 2021 were included. Characteristics, symptoms, coronary related adverse events and CTA information were reviewed by medical records. Separate multivariable cumulative logistic regressions were performed, using the stenosis severity in each of the four coronaries as individual responses and as a combined patient clustered response. Finally, we identified 207 adult patients with AAOCA, the prevalence of AAOCA is 0.23% (207/90,501). Moreover, this study found no significant association between AAOCA and CAD. AAOCA did not contribute to higher rates of hospitalization or adverse cardiac events, including calcification. CONCLUSION: AAOCA is a rare congenital disease that is not associated with increased presence of obstructive CAD in adults.

Giant thoracic hematoma post-transradial coronary angiography: a case report and review of the literature.

BACKGROUND: Although there are cardiac interventional procedures, certain transradial access complications might be life-threatening. CASE PRESENTATION: A 67-year-old male was admitted for coronary angiography due to chest tightness and shortness of breath on exertion. Hours after the right transradial access angiography, the patients complained the right side of chest pain. Emergent chest X-ray revealed a giant mass in the right chest. The right radial artery was reaccessed and subsequent arteriograms confirmed that the presence of a rupture of the branch of right internal mammary artery. Simultaneously, a microcoil was implanted to seal the perforation. The perforation caused a thoracic hematoma measuring 13.8 cm × 6.7 cm, along with a decrease in hemoglobin concentration from 14.1 g/dL to a minimum of 7.8 g/dL. Additionally, the drainage of the hematoma and red blood cells transfusion were carried out. Further, the patient underwent ascending aortic replacement, aortic valve replacement, mitral valve replacement, and thoracic hematoma removal. Postoperative echocardiography showed that the prosthetic valves were properly positioned and functioning normally. The patient recovered well after the surgery and remained event-free during the latest 14moth follow-up period. CONCLUSIONS: Vascular perforation and subsequent hematoma might occur due to guidewire maneuvering during transradial approach. Awareness of prevention, early recognition and management of access complications may help reduce the occurrence and severity of complications related to the transradial approach.

Hospitalized patients with isolated distal deep vein thrombosis: anticoagulation therapy or not?

BACKGROUND: Isolated distal deep vein thrombosis (IDDVT), a disease frequently detected in hospitalized patients, can progress to proximal deep vein thrombosis (PDVT) and pulmonary embolism (PE). Here, we evaluated the effects of anticoagulation in hospitalized IDDVT patients. METHODS: We conducted a retrospective study in our hospital and enrolled hospitalized IDDVT patients diagnosed by compression ultrasonography (CUS) from January to December 2020. Participants were divided into anticoagulation (AC) and non-anticoagulation (non-AC) groups. After propensity score matching (PSM), multivariate Cox regression analyses were performed to assess whether anticoagulation was associated with PDVT/PE, and all-cause mortality. RESULTS: A total of 426 IDDVT inpatients with CUS follow-up were screened from 1502 distal DVT patients and finally enrolled. The median age was 67 years with 51.4% males and 15.5% cancer patients. The median follow-up was 11.6 months. There were 288 and 138 patients treated with or without anticoagulants, respectively. Patients in the non-AC group had less body mass index and more comorbidities. Patients in the AC group were treated with rivaroxaban or dabigatran (52.1%), low molecular weight heparin (42.7%), and warfarin (5.2%). The PSM generated 111 pairs of well-matched IDDVT patients with or without anticoagulation. The Kaplan-Meier analysis demonstrated that neither the incidence of PDVT/PE (5.4% vs. 2.7%, log-rank p = 0.313) nor all-cause mortality (27.9% vs. 18.9%, log-rank p = 0.098) was significant different between groups. Anticoagulation was not associated with PDVT/PE and all-cause mortality in the multivariable Cox regression analyses using the matched cohorts. The main risk factors for all-cause mortality were age, malignancy history, BMI, sepsis, heart failure, and white blood cell (WBC) count. CONCLUSIONS: In hospitalized IDDVT patients, the thrombosis extension rate to PDVT/PE was low. Anticoagulation did not reduce the incidence of thrombosis extension of IDDVT and was not associated with all-cause mortality.

Risk factors for incomplete thrombosis in false lumen in sub-acute type B aortic dissection post-TEVAR.

There is scarce information about the risk factors for incomplete false lumen thrombosis (FLT) among type B aortic dissection (AD) patients, particularly in the sub-acute phase following thoracic endovascular aortic repair (TEVAR). We enrolled consecutive sub-acute type B AD patients at Xinqiao Hospital (Chongqing, China) from May 2010 to December 2019. Patients with severe heart failure, cancer, and myocardial infarction were excluded. The postoperative computed tomography angiography (CTA) data were extracted from the most recent follow-up aortic CTA. Multivariate logistic regressions were applied to identify the association between FLT and clinical or imaging factors. Fifty-five subjects were enrolled in our study. Twelve participants showed complete FLT, and 2 of these died during the follow-up, while 8 patients died in incomplete FLT group. In the multivariate analysis, maximum abdominal aorta diameter (OR 1.20, 95% CI 1.016-1.417 p = 0.032) and the number of branches arising from the false lumen (FL) (OR 15.062, 95% 1.681-134.982 p = 0.015) were significantly associated with incomplete FLT. The C-statistics was 0.873 (95% CI 0.773-0.972) for the model. The FL diameter (p < 0.001) was significantly shorter following TEVAR, while the true lumen diameter (p < 0.001) and maximum abdominal aorta diameter (p = 0.011) were larger after the aortic repair. There were 21.8% of sub-acute type B AD patients presented complete FLT post-TEVAR. Maximum abdominal aorta diameter and the number of branches arising from the FL were independent risk factors for incomplete FLT. The true lumen diameter, maximum abdominal aorta diameter, and FL diameter changed notably following TEVAR.

The association between periodontal disease and the risk of myocardial infarction: a pooled analysis of observational studies.

BACKGROUND: Several meta-analyses have indicated that periodontal disease (PD) are related to cardiovascular diseases (CVDs). However, the association between PD and myocardial infarction (MI) remains controversial. Here we aimed to assess the association between PD and MI by meta-analysis of observational studies. METHODS: PubMed, EMBASE and the Cochrane Library were searched through July, 2016. Observational studies including cohort, cross-sectional and case-control studies reporting odds ratio (OR) or relative risk (RR) with 95% confidence intervals (CIs) were included in the analysis. Either fixed or random-effects model were applied to evaluate the pooled risk estimates. Sensitivity and subgroup analyses were also carried out to identify the sources of heterogeneity. Publication bias was assessed by the Begg's, Egger's test and funnel plot. RESULTS: We included 22 observational studies with 4 cohort, 6 cross-sectional and 12 case-control studies, including 129,630 participants. Patients with PD have increased risk of MI (OR 2.02; 95% CI 1.59-2.57). Substantial heterogeneity in risk estimates was revealed. Subgroup analyses showed that the higher risk of MI in PD patients exists in both cross-sectional studies (OR 1.71; 95% CI 1.07-2.73) and case-control studies (OR 2.93; 95% CI 1.95-4.39), and marginally in cohort studies (OR 1.18; 95% CI 0.98-1.42). Further, subgroup meta-analyses by location, PD exposure, participant number, and study quality showed that PD was significantly associated with elevated risk of MI. CONCLUSION: Our meta-analysis suggested that PD is associated with increased risk of future MI. However, the causative relation between PD and MI remains not established based on the pooled estimates from observational studies and more studies are warranted.

Pro-atherogenic role of smooth muscle Nox4-based NADPH oxidase.

UNLABELLED: Nox4-based NADPH oxidase is a major reactive oxygen species-generating enzyme in the vasculature, but its role in atherosclerosis remains controversial. OBJECTIVE: Our goal was to investigate the role of smooth muscle Nox4 in atherosclerosis. APPROACH AND RESULTS: Atherosclerosis-prone conditions (disturbed blood flow and Western diet) increased Nox4 mRNA level in smooth muscle of arteries. To address whether upregulated smooth muscle Nox4 under atherosclerosis-prone conditions was directly involved in the development of atherosclerosis, mice carrying a human Nox4 P437H dominant negative mutation (Nox4DN), specifically in smooth muscle, were generated on a FVB/N ApoE deficient genetic background to counter the effect of increased smooth muscle Nox4. Nox4DN significantly decreased aortic stiffness and atherosclerotic lesions, with no effect on blood pressure. Gene analysis indicated that soluble epoxide hydrolase 2 (sEH) was significantly downregulated in Nox4DN smooth muscle cells (SMC), at both mRNA and protein levels. Downregulation of sEH by siRNA decreased SMC proliferation and migration, and suppressed inflammation and macrophage adhesion to SMC. CONCLUSIONS: Downregulation of smooth muscle Nox4 inhibits atherosclerosis by suppressing sEH, which, at least in part, accounts for inhibition of SMC proliferation, migration and inflammation.

Role of smooth muscle Nox4-based NADPH oxidase in neointimal hyperplasia.

UNLABELLED: Elevated levels of reactive oxygen species (ROS) in the vascular wall play a key role in the development of neointimal hyperplasia. Nox4-based NADPH oxidase is a major ROS generating enzyme in the vasculature, but its roles in neointimal hyperplasia remain unclear. OBJECTIVE: Our purpose was to investigate the role of smooth muscle cell (SMC) Nox4 in neointimal hyperplasia. APPROACH AND RESULTS: Mice overexpressing a human Nox4 mutant form, carrying a P437H dominant negative mutation (Nox4DN) and driven by SM22α promoter, to achieve specific expression in SMC, were generated in a FVB/N genetic background. After wire injury-induced endothelial denudation, Nox4DN had significantly decreased neointima formation compared with non-transgenic littermate controls (NTg). ROS production, serum-induced proliferation and migration, were significantly decreased in aortic SMCs isolated from Nox4DN compared with NTg. Both mRNA and protein levels of thrombospondin 1 (TSP1) were significantly downregulated in Nox4DN SMCs. Downregulation of TSP1 by siRNA decreased cell proliferation and migration in SMCs. Similar to Nox4DN, downregulation of Nox4 by siRNA significantly decreased TSP1 expression level, cell proliferation and migration in SMCs. CONCLUSIONS: Downregulation of smooth muscle Nox4 inhibits neointimal hyperplasia by suppressing TSP1, which in part can account for inhibition of SMC proliferation and migration.

Angiotensin II-induced TLR4 mediated abdominal aortic aneurysm in apolipoprotein E knockout mice is dependent on STAT3.

Abdominal Aortic Aneurysm (AAA) is a major cause of mortality and morbidity in men over 65 years of age. Male apolipoprotein E knockout (ApoE(-/-)) mice infused with angiotensin II (AngII) develop AAA. Although AngII stimulates both JAK/STAT and Toll-like receptor 4 (TLR4) signaling pathways, their involvement in AngII mediated AAA formation is unclear. Here we used the small molecule STAT3 inhibitor, S3I-201, the TLR4 inhibitor Eritoran and ApoE(-/-)TLR4(-/-) mice to evaluate the interaction between STAT3 and TLR4 signaling in AngII-induced AAA formation. ApoE(-/-) mice infused for 28 days with AngII developed AAAs and increased STAT3 activation and TLR4 expression. Moreover, AngII increased macrophage infiltration and the ratio of M1 (pro-inflammatory)/M2 (healing) macrophages in aneurysmal tissue as early as 7-10 days after AngII infusion. STAT3 inhibition with S3I-201 decreased the incidence and severity of AngII-induced AAA formation and decreased MMP activity and the ratio of M1/M2 macrophages. Furthermore, AngII-mediated AAA formation, MMP secretion, STAT3 phosphorylation and the ratio of M1/M2 macrophages were markedly decreased in ApoE(-/-)TLR4(-/-) mice, and in Eritoran-treated ApoE(-/-) mice. TLR4 and pSTAT3 levels were also increased in human aneurysmal tissue. These data support a role of pSTAT3 in TLR4 dependent AAA formation and possible therapeutic roles for TLR4 and/or STAT3 inhibition in AAA.

Nox2 mediates high fat high sucrose diet-induced nitric oxide dysfunction and inflammation in aortic smooth muscle cells.

Diet-induced obesity and metabolic syndrome are important contributors to cardiovascular diseases. The decreased nitric oxide (NO) bioactivity in endothelium and the impaired response of smooth muscle cell (SMC) to NO significantly contribute to vascular pathologies, including atherosclerosis and arterial restenosis after angioplasty. Sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA) is an important mediator of NO function in both endothelial cells and SMCs, and its irreversible oxidation impairs its stimulation by NO. We used C57BL/6J mice fed a high fat high sucrose diet (HFHSD) to study the role of SMC SERCA in diet-induced obesity and metabolic syndrome. We found that HFHSD upregulated Nox2 based NADPH oxidase, induced inflammation, increased irreversible SERCA oxidation, and suppressed the response of aortic SERCA to NO. Cultured aortic SMCs from mice fed HFHSD showed increased reactive oxygen species production, Nox2 upregulation, irreversible SERCA oxidation, inflammation, and a decreased ability of NO to inhibit SMC migration. Overexpression of wild type SERCA2b or downregulation of Nox2 restored NO-mediated inhibition of migration in SMCs isolated from HFHSD-fed mice. In addition, tumor necrosis factor alpha (TNFα) increased Nox2 which induced SERCA oxidation and inflammation. Taken together, Nox2 induced by HFHSD plays significant roles in controlling SMC responses to NO and TNFα-mediated inflammation, which may contribute to the development of cardiovascular diseases in diet-induced obesity and metabolic syndrome.

B-type natriuretic peptide levels at admission predict the prognosis of patients with infective endocarditis undergoing cardiac surgery.

Purpose: The objective of this study was to explore the relationship between elevated B-type natriuretic peptide (BNP) levels and the prognosis of patients with infective endocarditis (IE) undergoing cardiac surgery. Methods: In total, 162 IE patients with recorded BNP levels upon admission were included in the present study. The primary end point was all-cause mortality. Results: Multivariate Cox analysis revealed a significant association between log BNP and all-cause mortality. Kaplan-Meier analysis revealed a poorer prognosis for patients with BNP levels ≥ the 75th percentile. Furthermore, the linear trend test indicated a significant link between BNP quartiles and the primary end point within the models. Conclusion: Elevated BNP levels upon admission could predict all-cause mortality in IE patients undergoing cardiac surgery.

Infective endocarditis (IE) refers to an infection affecting the heart lining, heart valves or blood vessels. Despite advancements in medical and surgical interventions, the overall mortality rate remains high among IE patients after surgery. B-type natriuretic peptide (BNP) is a peptide released in response to increased stress on the ventricular and atrial walls and is commonly used as a biomarker for heart failure. This study was aimed to assess the potential of BNP in predicting all-cause mortality in IE patients. The results indicate that elevated BNP levels upon admission could predict a worse prognosis following endocarditis surgery. Additionally, elevated BNP levels upon admission were associated with an increased risk of death.

Description and Prognosis of Patients with Recovered Dilated Cardiomyopathy: A Retrospective Cohort Study.

Background: With the recent advances in the treatment of heart failure (HF), it is intriguing that a very small number of patients with dilated cardiomyopathy (DCM) have been observed as being fully recovered. However, knowledge of the progression and prognosis of patients with recovered DCM remains sparse. Herein, we conducted this study to investigate the clinical characteristics and prognosis of patients with recovered DCM. Methods: Consecutive patients with recovered DCM referred to our hospital between March 2009 and May 2021 were included. The recovered DCM patients were categorized into relapse and non-relapse groups. The primary endpoint was all-cause death, and the secondary endpoint was HF re-hospitalization during follow-up. Multivariate analyses were performed to identify predictors of relapse among recovered DCM patients. Kaplan-Meier analyses were used to assess the prognostic significance of relapse. Results: A comparatively large cohort of 122 recovered DCM patients from 10,029 DCM patients was analyzed. During a median follow-up duration of 53.5 months, the relapse rate among recovered DCM patients was 15.6% (19/122). Age (odds ratio, OR 1.079, 95% confidence interval, CI: 1.014-1.148; p = 0.017), systolic blood pressure (SBP) at diagnosis (OR 0.948, 95% CI: 0.908-0.990; p = 0.015) and changes in left ventricular ejection fraction from diagnosis to recovery ( Δ LVEF) (OR 0.898, 95% CI: 0.825-0.978; p = 0.013) were identified as predictors of relapse. Furthermore, among 122 patients, 5 (4.1%) experienced death, and 12 (9.8%) underwent HF re-hospitalization. Four deaths occurred in the relapse group, with one in the non-relapse group. All deaths were attributed to cardiovascular events. The long-term prognosis of the relapse group was significantly worse compared to the non-relapse group by Kaplan-Meier analysis (p < 0.001 based on the log-rank test). Multivariate analyses significantly associated relapse with all-cause mortality in recovered DCM patients (hazard ratio, HR 7.738, 95% CI: 1.892-31.636; p = 0.004). Conclusions: Recovered DCM patients are at risk of relapse. Older age, lower SBP, and smaller Δ LVEF were independently associated with relapse in recovered DCM patients. Relapse after recovery was related to an unfavorable long-term prognosis.

Sodium-glucose cotransporter 2 inhibitors attenuate vascular calcification by suppressing endoplasmic reticulum protein thioredoxin domain containing 5 dependent osteogenic reprogramming.

AIMS: Vascular calcification is strongly linked to the development of major adverse cardiovascular events, but effective treatments are lacking. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are an emerging category of oral hypoglycemic drugs that have displayed marked effects on metabolic and cardiovascular diseases, including recently reported vascular medial calcification. However, the roles and underlying mechanisms of SGLT2 inhibitors in vascular calcification have not been fully elucidated. Thus, we aimed to further determine whether SGLT2 inhibitors protect against vascular calcification and to investigate the mechanisms involved. METHODS AND RESULTS: A computed tomography angiography investigation of coronary arteries from 1554 patients with type 2 diabetes revealed that SGLT2 inhibitor use was correlated with a lower Agatston calcification score. In the vitamin D3 overdose, 5/6 nephrectomy chronic kidney disease-induced medial calcification and Western diet-induced atherosclerotic intimal calcification models, dapagliflozin (DAPA) substantially alleviated vascular calcification in the aorta. Furthermore, we showed that DAPA reduced vascular calcification via Runx2-dependent osteogenic transdifferentiation in vascular smooth muscle cells (VSMCs). Transcriptome profiling revealed that thioredoxin domain containing 5 (TXNDC5) was involved in the attenuation of vascular calcification by DAPA. Rescue experiments showed that DAPA-induced TXNDC5 downregulation in VSMCs blocked the protective effect on vascular calcification. Furthermore, TXNDC5 downregulation disrupted protein folding-dependent Runx2 stability and promoted subsequent proteasomal degradation. Moreover, DAPA downregulated TXNDC5 expression via amelioration of oxidative stress and ATF6-dependent endoplasmic reticulum stress. Consistently, the class effects of SGLT2 inhibitors on vascular calcification were validated with empagliflozin in intimal and medial calcification models. CONCLUSIONS: SGLT2 inhibitors ameliorate vascular calcification through blocking endoplasmic reticulum stress-dependent TXNDC5 upregulation and promoting subsequent Runx2 proteasomal degradation, suggesting that SGLT2 inhibitors are potentially beneficial for vascular calcification treatment and prevention.

Predicting Hospital Readmissions in Patients Receiving Novel-Dose Sacubitril/Valsartan Therapy: A Competing-Risk, Causal Mediation Analysis.

Backgrounds: Our study aimed to identify and predict patients with heart failure (HF) taking novel-dose Sacubitril/Valsartan (S/V) at risk for all-cause readmission, as well as investigate the possible role of left ventricular reverse remodeling (LVRR). Methods and results: There were 464 patients recruited from December 2017 to September 2021 in our hospital with a median follow-up of 660 days (range, 17-1494). Competing risk analysis with Gray's Test showed statistically significant differences in all-cause readmission (p-value< .001) across the three different dose groups. Models 1 and 2 were developed based on the results of univariable competing risk analysis, least absolute shrinkage and selection operator approach, backward stepwise regression, and multivariable competing risk analysis. The internal verification (data-splitting method) indicated that Model 1 had better discrimination, calibration, and clinical utility. The corresponding nomogram showed that patients aged 75 years and above, or taking the lowest-dose S/V (≤50 mg twice a day), or diagnosed with ventricular tachycardia, or valvular heart disease, or chronic obstructive pulmonary disease, or diabetes mellitus were at the highest risk of all-cause readmission. In the causal mediation analysis, LVRR was considered as a critical mediator that negatively affected the difference of novel-dose S/V in readmission. Conclusions: A significant association was detected between novel-dose S/V and all-cause readmission in HF patients, in part negatively mediated by LVRR. The web-based nomogram could provide individual prediction of all-cause readmission in HF patients receiving novel-dose S/V. The effects of different novel-dose S/V are still needed to be explored further in the future.

Impact of coronary artery disease in patients with hypertrophic cardiomyopathy.

BACKGROUND: Atherosclerotic coronary artery disease (CAD) often occurs concurrently with hypertrophic cardiomyopathy (HCM). However, the influence of concomitant CAD has not been fully assessed in patients with HCM. METHODS: Invasive or computed tomography coronary angiography was performed in 461 patients with HCM at our hospital to determine the presence and severity of CAD from March 2010 to April 2022. The primary end points were all-cause, cardiovascular, and sudden cardiac deaths. The survival of HCM patients with severe CAD was compared with that of HCM patients without severe CAD. RESULTS: Of 461 patients with HCM, 235 had concomitant CAD. During the median (interquartile range) follow-up of 49 (31-80) months, 75 patients (16.3%) died. The 5-year survival estimates were 64.3%, 82.5%, and 86.0% for the severe, mild-to-moderate, and no-CAD groups, respectively (log-rank, p = 0.010). Regarding the absence of cardiovascular death, the 5-year survival estimates were 68.5% for patients with severe CAD, 86.4% for patients with mild-to-moderate CAD, and 90.2% for HCM patients with no CAD (log-rank, p = 0.001). In multivariate analyses, severe CAD was associated with all-cause and cardiovascular death after adjusting for age, left ventricular ejection fraction, hypertension, and atrial fibrillation. CONCLUSIONS: This study showed a worse prognosis among HCM patients with severe CAD than among HCM patients without severe CAD. Therefore, timely recognition of severe CAD in HCM patients and appropriate treatment are important.

An essential role for the Id1/PI3K/Akt/NFkB/survivin signalling pathway in promoting the proliferation of endothelial progenitor cells in vitro.

The enhancement of re-endothelialisation is a critical therapeutic option for repairing injured blood vessels. Endothelial progenitor cells (EPCs) are the major source of cells that participate in endothelium repair and contribute to re-endothelialisation by reducing neointima formation after vascular injury. The over-expression of the inhibitor of differentiation or DNA binding 1 (Id1) significantly improved EPC proliferation. This study aimed to investigate the effects of Id1 on the phosphatidylinositol-3-kinase (PI3K)/Akt/nuclear factor kappa B (NFκB)/survivin signalling pathway and its significance in promoting EPC proliferation in vitro. Spleen-derived EPCs were cultured as previously described. Id1 was presented at low levels in EPCs, and was rapidly up-regulated by stimulation with vascular endothelial growth factor. We demonstrated that transient transfection of Id1 into EPCs activated the PI3K/Akt/NFκB/survivin signalling pathway and promoted EPC proliferation. The proliferation of EPCs was extensively inhibited by silencing of endogenous Id1, and knockdown of Id1 expression led to suppression of PI3K/Akt/NFκB/survivin signalling pathway in EPCs. In addition, blockade by the PI3K-specific inhibitor LY294002, Akt inhibitor, the NFκB inhibitor BAY 11-7082, the survivin inhibitor Curcumin, or the survivin inhibitor YM155 reduced the effects of Id1 transfection. These results suggest that the Id1/PI3K/Akt/NFκB/survivin signalling pathway plays a critical role in EPC proliferation. The Id1/PI3K/Akt/NFκB/survivin signalling pathway may represent a novel therapeutic target in the prevention of restenosis after vascular injury.

Maintenance of recovered dilated cardiomyopathy patients with half-dose neurohumoral blockades (MED-CHARM): A protocol for an open-label, pilot, randomized trial.

Dilated cardiomyopathy (DCM) has brought great damage to the patients' health and social economy. The number of patients with recovered dilated cardiomyopathy (recDCM) has increased over the years as treatment progresses. However, there is a lack of relevant evidence to support the clinical management of patients with recDCM, thereby, the recommendations in guidelines remains sparse. Accordingly, the exploration of recDCM is important to improve patient prognosis and reduce societal burden. This is an open-label, randomized controlled, prospective study that will compare the safety and efficacy of original dose and halved dose of neurohumoral blockades for patients with recDCM. Methods: An open-label, randomized controlled, prospective study will be conducted among eligible patients with recDCM. During the pilot study phase, we will recruit 50 patients. The primary endpoint is hospitalization for heart failure or heart failure relapse within 12 months. Secondary endpoint is major adverse cardiovascular events, including cardiovascular mortality, myocardial infarction, stroke, sustained atrial tachycardia, or ventricular tachycardia. The results will be analyzed using intention-to-treatment analysis. Discussion: The study will provide important evidence of whether it is safe and effective to halve the dosage of neurohumoral blockades in recDCM patients. Trial registration number: ChiCTR2100054051 (www.chictr.org.cn).

Effect of social app-assisted education and support on glucose control in patients with coronary heart disease and diabetes mellitus.

Background: Social app-assisted education and support may facilitate diabetes self-management. We aim to evaluate the effect of WeChat, a popular social app, on glycemic control in patients with coronary heart disease (CHD) and diabetes mellitus (DM). Methods: We conducted a parallel-group, open-label, randomized clinical trial that included 160 patients with both CHD and diabetes mellitus from a tertiary hospital in China. The intervention group (n = 80) received educational materials (information on glucose monitoring, drug usage, medication, and lifestyle) and reminders in response to individual blood glucose values via WeChat. The control group (n = 80) received usual care. The primary outcome was a change in glycated hemoglobin (HbA1C) levels over 3 months. Secondary outcomes included fasting blood glucose (FBG), systolic blood pressure, and low-density lipoprotein (LDL) cholesterol from baseline to 3 months. Analysis was conducted using a linear mixed model. Results: The intervention group had a greater reduction in HbA1C (-0.85 vs. 0.15%, between-group difference: -1.00%; 95% CI -1.31 to -0.69%; p < 0.001) compared with the control group. Change in fasting blood glucose was larger in the intervention group (-1.53 mmol/L; 95% CI -1.90 to -1.17; p < 0.001) and systolic blood pressure (-9.06 mmHg; 95% CI -12.38 to -5.73; p < 0.001), but not LDL (between-group difference, -0.08 mmol/L; 95% CI -0.22 to 0.05; p = 0.227). Conclusion: The combination of social app with education and support resulted in better glycemic control in patients with CHD and DM. These results suggest that education and support interaction via social app may benefit self-management in CHD and DM.

Prognostic Significance of B-Type Natriuretic Peptide in Patients With Left Ventricular Thrombus.

Background and Aims: There is sparse information on the prognostic value of B-type natriuretic peptide (BNP) for the outcomes in patients with left ventricular thrombus (LVT). Methods: Patients diagnosed with LVT by transthoracic echocardiography between November 2009 to July 2020 at our institution were included. The endpoints were all-cause mortality and systemic embolism. Results: Ninety-two subjects were finally included in the study. The mean age of the cohort was 56.73 ± 14.12, and 80.4% of the patients were male. The median BNP (1st quartile-3rd quartile) was 437.5 (112.74-1317.5). The total all-cause mortality rate was 30.44% (28/92), and the 1-year, 2-year, and 3-year cumulative survival rates were 85.4, 75.5, and 66.5%, respectively. Systemic embolism was identified in 10 subjects. COX multivariate analysis showed that Log BNP (HR, 4.16; 95%CI, 1.81-9.56; P = 0.001) and BMI (HR, 0.86; 95%CI, 0.73-0.99; P = 0.048) were significantly associated with all-cause mortality. In addition, patients with BNP levels in the upper median (≥ 437.5 pg/ml) had significantly higher all-cause mortality rate compared to those with lower median BNP (<437.5 pg/ml; P = 0.004). The area under the receiver operating characteristic curve for BNP and all-cause mortality was 0.71. In the linear trend test, BNP quartiles were significantly related to all-cause mortality in all models, and the P-values for trend in models 1, 2, and 3 were 0.005, 0.006, and 0.048, respectively. Conclusion: BNP level is a prognostic factor for all-cause mortality in LVT patients, and elevated BNP is indicative of a higher risk of LVT.

Stabilization of Nrf2 leading to HO-1 activation protects against zinc oxide nanoparticles-induced endothelial cell death.

With the abundant production and wide application of zinc oxide nanoparticles (ZnONPs), the potential health risks of ZnONPs have raised serious concerns. Oxidative stress is recognized as the most important outcome of the toxicity induced by ZnONPs. The Nrf2-Keap1 system and its downstream antioxidative genes are the fundamental protective mechanisms for redox hemeostasis. However, the detailed mechanisms of Nrf2 activation in ZnONPs-treated endothelial cells and murine blood vessels have yet to be elucidated. Herein, we show that Nrf2 was activated and played a negative role in cell death induced by ZnONPs. Moreover, we demonstrate that HO-1 was the most extensively upregulated antioxidative gene-activated by Nrf2. Forced overexpression of HO-1, pharmacological activation of HO-1 with the agonists RTA-408 (omaveloxolone, an FDA-approved drug) and RTA-402 repressed cell death, and treatment with HO-1 antagonist SnPP exacerbated the cell death. Importantly, loss of HO-1 diminished the cytoprotective role induced by Nrf2 in ZnONPs-treated HUVEC cells, indicating that the Nrf2-HO-1 axis was the crucial regulatory mechanism for the antioxidative response in the context of ZnONPs-induced endothelial damage. Mechanistically, we demonstrate that the p62-Keap1 axis was not involved in the activation of Nrf2. Intriguingly, the degradation half-life of Nrf2 in HUVEC cells was increased from less than 1 h under quiescent conditions to approximately 6 h under ZnONPs treatment condition; moreover, ZnONPs treatment induced activation of Nrf2/HO-1 and accumulation of ubiquitin in the aorta ventralis of mouse, suggesting that the ubiquitin-proteasome system had been perturbed, which subsequently led to the stabilization of Nrf2 and activation of HO-1. This study might contribute to a better understanding of ZnONPs-associated toxicity.

A novel echocardiographic parameter to identify individuals susceptible to acute mountain sickness.

BACKGROUND: Acute mountain sickness (AMS) may cause life-threatening conditions. This study aimed to screen echocardiographic parameters at sea level (SL) to identify predictors of AMS development. METHODS: Overall, 106 healthy men were recruited at SL and ascended to 4100 m within 7 days by bus. Basic characteristics, physiological data, and echocardiographic parameters were collected both at SL and 4100 m above SL. AMS was identified by 2018 Lake Louise Questionnaire Score. RESULTS: After acute high altitude exposure (AHAE), 33 subjects were diagnosed with AMS and exhibited lower lateral mitral valve tissue motion annular displacement (MV TMADlateral) at SL than AMS-free subjects (13.09 vs. 13.89 mm, p = 0.022). MV TMADlateral at SL was significantly correlated with AMS occurrence (OR = 0.717, 95% CI: 0.534-0.964, p = 0.028). The MV TMADlateral<13.30-mm group showed over 4-fold risk for AMS development versus the MV TMADlateral≥13.30-mm group. After AHAE, the MV TMADlateral<13.30-mm group had increased HR (64 vs. 74 bpm, p = 0.001) and right-ventricular myocardial performance index (0.54 vs. 0.69, p = 0.009) and decreased left ventricular global longitudinal strain (-21.50 vs. -20.23%, p = 0.002), tricuspid valve E/A ratio (2.11 vs. 1.89, p = 0.019), and MV E-wave deceleration time (169.60 vs. 156.90 ms, p = 0.035). CONCLUSION: MV TMADlateral at SL was a potential predictor of AMS occurrence and might be associated with differential alterations of ventricular systolic and diastolic functions in subjects with different MV TMADlateral levels at SL after AHAE.