The Impacts of Nirmatrelvir-Ritonavir on Myocardial Injury and Long-Term Cardiovascular Outcomes in Hospitalized Patients with COVID-19 amid the Omicron Wave of the Pandemic.

PURPOSE: Even though nirmatrelvir-ritonavir can improve the short-term morbidity and mortality in COVID-19 patients, the effects of this treatment on long-term major adverse cardiovascular events (MACEs), especially myocardial injury, remains undetermined. METHODS: This prospective cohort study identified hospitalized adult patients with COVID-19 between April 19, 2022, and June 9, 2022, amid the omicron wave of the pandemic. Matched nirmatrelvir-ritonavir-treated and non-treated cohorts were formed using the propensity score matching method. The primary outcome of this study was the incidence of MACEs (cardiovascular death, myocardial infarction, stroke, new-onset heart failure or heart failure hospitalization or ventricular arrhythmia) from 30 days to 16 months after the diagnosis of COVID-19. RESULTS: Two 949-patient cohorts with balanced baseline characteristics were formed by propensity score matching. Patients with nirmatrelvir-ritonavir, compared to those untreated, had a lower level of troponin I peak as well as the incidence of troponin I elevation. During the follow-up period, 59 patients in the nirmatrelvir-ritonavir group and 86 patients in the control group developed MACEs (P = 0.020). Regarding specific constituents of MACEs, the differences are mainly reflected in new-onset heart failure or heart failure hospitalization. COVID-19 clinical severity and troponin I peak were the independent predictors, while nirmatrelvir-ritonavir was the independent protective factor for the occurrence of MACEs in this population. CONCLUSION: Nirmatrelvir-ritonavir was effective in reducing myocardial injury as well as long-term adverse cardiovascular outcomes among hospitalized patients with COVID-19 amid the omicron wave of the pandemic.

The impacts of prophylactic anticoagulation therapy during hospitalization on long-term cardiovascular outcomes in high-risk COVID-19 patients amid the omicron wave of the pandemic.

Background: Although prophylactic anticoagulation therapy is suggested to be adopted in severe COVID-19 patients, its effects on the long-term cardiovascular (CV) outcomes, namely the risk of major adverse CV events(MACEs) in high-risk CV patients amid the omicron wave of the pandemic, remain unknown. Methods: We conducted this prospective cohort study of consecutive adults hospitalized COVID-19 between 19 April and 12 June 2022, COVID-19 patients with at least two CV risk factors or pre-existing CV diseases were enrolled. A propensity score matching(PSM) method was used to evaluated the effects of prophylactic anticoagulation therapy in hospital on long-term MACEs, including CV death, non-fatal myocardial infarction, non-fatal stroke, hospitalization due to unstable angina pectoris, coronary revascularization and arterial or venous thrombosis. Results: Two cohorts (with or without anticoagulants during hospitalization) of each 230 patients with balanced baseline characteristics were formed using PSM. During the 15-month follow-up period, 13 patients with anticoagulants and 29 patients without anticoagulants developed MACEs. Overall, the anticoagulation group had a significantly lower risk of MACEs than the control group (hazard ratio [HR] 0.431; 95 % confidence interval [CI]: 0.224-0.830, P = 0.010). Regarding specific constituents of MACEs, the differences were mainly reflected in arterial or venous thrombosis. The significantly lower HRs of overall MACEs were significantly observed in subgroup of age > 75 years, women, higher D dimer level, unvaccinated and non-nirmatrelvir-ritonavir prescribed patients. Conclusions: Prophylactic anticoagulation therapy during hospitalization was effective in reducing long-term MACEs among COVID-19 patients with CV risk factors or pre-existing CV diseases amid the omicron wave of the pandemic.

The initial timing and dosage pattern of sacubitril/valsartan in patients with acute myocardial infarction undergoing percutaneous coronary intervention.

BACKGROUND: In real-world clinical practice, the initiation and up-titration of sacubitril/valsartan remain challenging due to symptomatic hypotension in patients with acute myocardial infarction(AMI). The purpose of this study was to investigate the efficacy of different initial timing and dosage of sacubitril/valsartan in AMI patients. METHODS: This prospective and observational cohort study enrolled AMI patients treated with percutaneous coronary intervention(PCI), and were categorized according to the initial timing and average daily doses of sacubitril/valsartan prescription. The primary endpoint was defined as a composite of cardiovascular death, recurrent AMI, coronary revascularization, heart failure(HF) hospitalization and ischaemic stroke. Secondary outcomes included the new-onset HF, and the composite endpoints in AMI patients complicated with HF at baseline. RESULTS: The study population consisted of 915 AMI patients. After a median follow-up of 38 months, early use or high dosage of sacubitril/valsartan was associated with an improvement in primary endpoint as well as the incidence of new-onset HF. Early use of sacubitril/valsartan also ameliorated the primary endpoint in AMI patients with left ventricular ejection fraction(LVEF) ≤50% as well as LVEF>50%. Besides, early use of sacubitril/valsartan improved the clinical outcomes in AMI patients complicated with HF at baseline. The low dose was well tolerated and may be associated with similar outcomes compared with high dose under some circumstances(LVEF>50% or HF at baseline). CONCLUSIONS: Early use or high dosage of sacubitril/valsartan medication is associated with an improvement in clinical outcome. The low dose of sacubitril/valsartan is well tolerated and may be an acceptable alternative strategy.

Roles of oral microbiota and oral-gut microbial transmission in hypertension.

INTRODUCTION: Considerable evidence has linked periodontitis (PD) to hypertension (HTN), but the nature behind this connection is unclear. Dysbiosis of oral microbiota leading to PD is known to aggravate different systematic diseases, but the alteration of oral microbiota in HTN and their impacts on blood pressure (BP) remains to be discovered. OBJECTIVES: To characterize the alterations of oral and gut microbiota and their roles in HTN. METHODS: We performed a cross-sectional (95 HTN participants and 39 controls) and a 6-month follow-up study (52 HTN participants and 26 controls) to analyze the roles of oral and gut microbiota in HTN. Saliva, subgingival plaques, and feces were collected for 16S rRNA gene sequencing or metagenomic analysis. C57BL/6J mice were pretreated with antibiotics to deplete gut microbiota, and then transplanted with human saliva by gavage to test the impacts of abnormal oral-gut microbial transmission on HTN. RESULTS: BP in participants with PD was higher than no PD in both cross-sectional and follow-up cohort. Relative abundances of 14 salivary genera, 15 subgingival genera and 10 gut genera significantly altered in HTN and those of 7 salivary genera, 12 subgingival genera and 6 gut genera significantly correlated with BP. Sixteen species under 5 genera were identified as oral-gut transmitters, illustrating the presence of oral-gut microbial transmission in HTN. Veillonella was a frequent oral-gut transmitter stably enriched in HTN participants of both cross-sectional and follow-up cohorts. Saliva from HTN participants increased BP in hypertensive mice. Human saliva-derived Veillonella successfully colonized in mouse gut, more abundantly under HTN condition. CONCLUSIONS: PD and oral microbiota are strongly associated with HTN, likely through oral-gut transmission of microbes. Ectopic colonization of saliva-derived Veillonella in the gut may aggravate HTN. Therefore, precise manipulations of oral microbiota and/or oral-gut microbial transmission may be useful strategies for better prevention and treatment of HTN.

Characteristics, prognosis, and treatment response in HFpEF patients with high vs. normal ejection fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) patients varied by left ventricular ejection fraction (LVEF) have different clinical characteristics, prognosis, and treatment response. With data from our prospective HFpEF cohort, we assessed the possible relationship between clinical characteristics, outcome as well as treatment response and LVEF. Methods: We compared differences in baseline characteristics and clinical outcomes across LVEF categories (50%≤LVEF <60% vs. LVEF≥60%) in 1,502 HFpEF patients, and determined whether LVEF modified the treatment response. During 5-year follow-up, all-cause mortality was used as the primary endpoints, and composite endpoints (all-cause mortality or HF hospitalization) were set as the secondary endpoint. Results: Patients with higher LVEF were statistically older, more likely to be women and have a history of atrial fibrillation. Patients with lower LVEF category were more likely to have a history of coronary artery disease. The incidences of all-cause mortality and composite endpoints were higher in patients with higher LVEF. Also, LVEF modified the spironolactone treatment effect for the primary outcome and secondary endpoint with stronger estimated benefits at the lower LVEF category with respect to all-cause mortality (HR 0.734, 95% CI 0.541-0.997, P = 0.048) and all-cause mortality or HF hospitalization (HR 0.767, 95% CI 0.604-0.972, P = 0.029). Conclusion: The characteristics and outcomes of HFpEF patients varied substantially by LVEF. Patients with higher LVEF encountered more adverse events than those with lower LVEF. The potential efficacy of spironolactone was greatest at the lower category of LVEF spectrum in HFpEF.

Extracellular vesicles from hypoxia-preconditioned mesenchymal stem cells alleviates myocardial injury by targeting thioredoxin-interacting protein-mediated hypoxia-inducible factor-1α pathway.

BACKGROUND: Extracellular vesicles (EVs) derived from hypoxia-preconditioned (HP) mesenchymal stem cells (MSCs) have better cardioprotective effects against myocardial infarction (MI) in the early stage than EVs isolated from normoxic (NC)-MSCs. However, the cardioprotective mechanisms of HP-EVs are not fully understood. AIM: To explore the cardioprotective mechanism of EVs derived from HP MSCs. METHODS: We evaluated the cardioprotective effects of HP-EVs or NC-EVs from mouse adipose-derived MSCs (ADSCs) following hypoxia in vitro or MI in vivo, in order to improve the survival of cardiomyocytes (CMs) and restore cardiac function. The degree of CM apoptosis in each group was assessed by the terminal deoxynucleotidyl transferase dUTP nick end-labeling and Annexin V/PI assays. MicroRNA (miRNA) sequencing was used to investigate the functional RNA diversity between HP-EVs and NC-EVs from mouse ADSCs. The molecular mechanism of EVs in mediating thioredoxin-interacting protein (TXNIP) was verified by the dual-luciferase reporter assay. Co-immunoprecipitation, western blotting, and immunofluorescence were performed to determine if TXNIP is involved in hypoxia-inducible factor-1 alpha (HIF-1α) ubiquitination and degradation via the chromosomal region maintenance-1 (CRM-1)-dependent nuclear transport pathway. RESULTS: HP-EVs derived from MSCs reduced both infarct size (necrosis area) and apoptotic degree to a greater extent than NC-EVs from CMs subjected to hypoxia in vitro and mice with MI in vivo. Sequencing of EV-associated miRNAs showed the upregulation of 10 miRNAs predicted to bind TXNIP, an oxidative stress-associated protein. We showed miRNA224-5p, the most upregulated miRNA in HP-EVs, directly combined the 3' untranslated region of TXNIP and demonstrated its critical protective role against hypoxia-mediated CM injury. Our results demonstrated that MI triggered TXNIP-mediated HIF-1α ubiquitination and degradation in the CRM-1-mediated nuclear transport pathway in CMs, which led to aggravated injury and hypoxia tolerance in CMs in the early stage of MI. CONCLUSION: The anti-apoptotic effects of HP-EVs in alleviating MI and the hypoxic conditions of CMs until reperfusion therapy may partly result from EV miR-224-5p targeting TXNIP.

Initial Invasive or Conservative Strategy in Heart Failure With Preserved Ejection Fraction and Coronary Artery Disease.

Background: In patients with both heart failure with preserved ejection fraction (HFpEF) and coronary artery disease (CAD), whether adopting an initial invasive strategy benefits better in clinical outcomes compared with those who received an initial conservative strategy remains inconclusive. Methods: With data from the heart failure (HF) cohort study, we analyzed patients who had HFpEF and CAD amenable to the invasive intervention using propensity score matching of 1:1 ratio to compare the initial invasive strategy and the initial conservative strategy of medical therapy alone. The primary outcome was the composite endpoints of all-cause mortality or cardiovascular hospitalization, and the secondary outcome was all-cause mortality or cardiovascular hospitalization. Results: Of 1,718 patients, 706 were treated with the invasive strategy and 1,012 with the conservative strategy initially. Propensity score matching was used to assemble a matched cohort of 1,320 patients receiving the invasive intervention (660 patients) or the medical therapy alone (660 patients). With a follow-up of 5 years, 378 (57.3%) in the invasive-strategy group and 403 (61.1%) in the conservative-strategy group reached the primary endpoint, and there was no significant difference in the rate of the primary endpoint (P = 0.162). The initial invasive strategy only improved the secondary outcome of cardiovascular hospitalization (P = 0.035). Also, the multivariable Cox regression model revealed that antiplatelet therapy, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB), or statin prescription was associated with a decreased risk of the primary outcome. Conclusion: In this well-profiled, propensity-matched cohort of patients with HFpEF and CAD, the addition of invasive intervention to medical therapy did not improve the long-term composite of all-cause mortality or cardiovascular hospitalization.

Optimal management of blood glucose, blood pressure and atrial fibrillation to reduce the risk of heart failure with preserved ejection fraction.

BACKGROUND: Type 2 diabetes mellitus (T2DM), hypertension and atrial fibrillation (AF) are risk factors for heart failure with preserved ejection fraction (HFpEF). AIM: To examine the effects of the simultaneous control of all three conditions on new-onset HFpEF in this population. METHODS: This prospective cohort study enrolled 552 patients with T2DM, hypertension and AF, but without clinical signs or symptoms of heart failure. The participants were followed up for 5 years to examine the effects of glycaemic control (haemoglobin A1c: <7.0%, 7.0%-8.0% and >8.0%), blood pressure (BP) control (systolic BP: <120, 120-140 and >140 mmHg) or rhythm versus rate control for AF on new-onset HFpEF. RESULTS: With a follow up of 5 years, the new-onset HFpEF occurred in 62 of 552 enrolled participants. Among the different control level for diabetes, hypertension and AF, the intensive blood glucose (BG) control, poor BP control and rate control of AF had the highest risk of new-onset HFpEF, and the conservative BG control, intensive BP control and rhythm control of AF had the lowest risk of new-onset HFpEF. Multivariable Cox regression analysis showed that both poor BP control (hazard ratio (HR): 1.421, 95% confidence interval (CI): 1.013-1.992, P = 0.042) and rate control of AF (HR: 1.362, 95% CI: 1.006-1.821, P = 0.033) were independently associated with the development of new-onset HFpEF. CONCLUSION: This study demonstrated that, besides intensive BP control, conservative BG control and rhythm control of AF were crucial factors to delay the progression of HFpEF among patients with T2DM, hypertension and AF.

Incident Heart Failure in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention.

Background: The contemporary incidence of heart failure (HF) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains unclear. This prospective cohort study was designed to study the incidence and predictors of new-onset HF in CAD patients after PCI (ChiCTR1900023033). Methods: From January 2014 to December 2018, 3,910 CAD patients without HF history undergoing PCI were prospectively enrolled. Demographics, medical history, cardiovascular risk factors, cardiac parameters, and medication data were collected at baseline. Multivariable adjusted competing-risk regression analysis was performed to examine the predictors of incident HF. Results: After a median follow-up of 63 months, 497 patients (12.7%) reached the primary endpoint of new-onset HF, of which 179, 110, and 208 patients (36.0, 22.1, and 41.9%) were diagnosed as having HF with reduced ejection fraction (EF) (HFrEF), HF with mid-range EF (HFmrEF), and HF with preserved EF (HFpEF), respectively. Higher B-type natriuretic peptide (BNP) or E/e' level, lower estimated glomerular filtration rate (eGFR) level, and atrial fibrillation were the independent risk factors of new-onset HF. Gender (male) and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) prescription were the negative predictors of new-onset HF. Moreover, it was indicated that long-term ACEI/ARB therapy, instead of beta-blocker use, was linked to lower risks of development of all three HF subtypes (HFrEF, HFmrEF and HFpEF). Conclusions: This prospective longitudinal cohort study shows that the predominant subtype of HF after PCI is HFpEF and ACEI/ARB therapy is accompanied with reduced risks of incident HF across three subtypes.

VSTM1 regulates monocyte/macrophage function via the NF-κB signaling pathway.

OBJECTIVE: V-set and transmembrane domain-containing protein 1 (VSTM1) is negatively correlated with inflammation. However, its effect on atherosclerosis (AS) remains largely unexplored. In this study, we aimed to assess the effect of VSTM1 on the biological function of human peripheral blood mononuclear cells /macrophages stimulated by oxidized low-density lipoprotein (ox-LDL). METHODS: U937 cells were divided into three groups as follows: control group, pLenti-VSTM1 shRNA group (VSTM1 depletion), and pLenti-VSTM1 group (VSTM1 overexpression). Cellular migration, chemotaxis, apoptosis, and secretion of inflammatory factors of monocytes/macrophages stimulated by ox-LDL were studied. RESULTS: Overexpression of VSTM1 decreased the proliferation of U937 cells and induced cellular apoptosis. Depletion of VSTM1 enhanced the invasiveness and chemotaxis, increased the inflammatory response, and reduced the incidence of cell necrosis and apoptosis. Nuclear factor κ of B cells (NF-κB) was activated in VSTM1-depleted U937 cells. CONCLUSION: VSTM1 might play an important role in the activation of monocytes/macrophages and participate in the pathogenesis of AS via regulating NF-κB activity.

Irisin ameliorates doxorubicin-induced cardiac perivascular fibrosis through inhibiting endothelial-to-mesenchymal transition by regulating ROS accumulation and autophagy disorder in endothelial cells.

The dose-dependent toxicity to cardiomyocytes has been well recognized as a central characteristic of doxorubicin (DOX)-induced cardiotoxicity (DIC), however, the pathogenesis of DIC in the cardiac microenvironment remains elusive. Irisin is a new hormone-like myokine released into the circulation in response to exercise with distinct functions in regulating apoptosis, inflammation, and oxidative stress. Recent advances revealed the role of irisin as a novel therapeutic method and an important mediator of the beneficial effects of exercise in cardioprotection. Here, by using a low-dose long-term mouse DIC model, we found that the perivascular fibrosis was involved in its myocardial toxicity with the underlying mechanism of endothelial-to-mesenchymal transition (EndMT). Irisin treatment could partially reverse DOX-induced perivascular fibrosis and cardiotoxicity compared to endurance exercise. Mechanistically, DOX stimulation led to excessive accumulation of ROS, which activated the NF-κB-Snail pathway and resulted in EndMT. Besides, dysregulation of autophagy was also found in DOX-treated endothelial cells. Restoring autophagy flux could ameliorate EndMT and eliminate ROS. Irisin treatment significantly alleviated ROS accumulation, autophagy disorder, NF-κB-Snail pathway activation as well as the phenotype of EndMT by targeting uncoupling protein 2 (UCP2). Our results also initially found that irisin was mainly secreted by cardiomyocytes in the cardiac microenvironment, which was significantly reduced by DOX intervention, and had a protective effect on endothelial cells in a paracrine manner. In summary, our study indicated that DOX-induced ROS accumulation and autophagy disorders caused an EndMT in CMECs, which played a role in the perivascular fibrosis of DIC. Irisin treatment could partially reverse this phenomenon by regulating UCP2. Cardiomyocytes were the main source of irisin in the cardiac microenvironment. The current study provides a novel perspective elucidating the pathogenesis and the potential treatment of DIC.

Predictive and prognostic value of v-set and transmembrane domain-containing 1 expression in monocytes for coronary artery disease.

The aim of this study was to investigate the correlation between v-set and transmembrane domain-containing 1 (VSTM1) expression and incidence of major adverse cardiac events (MACE) in patients with coronary heart disease (CHD). A total of 310 patients were divided into a non-acute coronary syndrome (non-ACS) group (containing the stable angina group, and the asymptomatic coronary artery diseaseand other patients group) and an ACS group (containing unstable angina and acute myocardial infarction patients). Monocytic VSTM1 expression levels (assessed via average fluorescence intensity derived from antibody binding to VSTM1) in each group were detected and analyzed. The cut-off value of monocytic VSTM1 expression to predict the onset of ACS and MACE was confirmed. VSTM1 expression in monocytes from the ACS group was lower than that of the non-ACS group. The incidence of MACEs in the high VSTM1-expression group was much less than that of those in the low VSTM1 expression group at the 1 year follow-up stage. VSTM1 expression had an independent-inversed association with increased incidence of MACE and ACS. VSTM1 expression in monocytes may help to predict the occurrence of ACS in patients with CHD, and moreover it may provide the means to evaluate MACE prognosis during CHD patient follow-up.

MiR-21-3p Inhibits Adipose Browning by Targeting FGFR1 and Aggravates Atrial Fibrosis in Diabetes.

A relationship between excess epicardial adipose tissue (EAT) and the risk of atrial fibrillation (AF) has been reported. Browning of EAT may be a novel approach for the prevention or treatment of AF by attenuating atrial fibrosis. Previous studies have identified microRNA-21 (miR-21) as a regulatory factor in atrial fibrosis. The present study examined the role of different subtypes of miR-21 in adipose browning and atrial fibrosis under hyperglycemic conditions. Wild type and miR-21 knockout C57BL/6 mice were used to establish a diabetic model via intraperitoneal injection of streptozotocin. A coculture model of atrial fibroblasts and adipocytes was also established. We identified miR-21-3p as a key regulator that controls adipocyte browning and participates in atrial fibrosis under hyperglycemic conditions. Moreover, fibroblast growth factor receptor (FGFR) 1, a direct target of miR-21-3p, decreased in this setting and controlled adipose browning. Gain and loss-of-function experiments identified a regulatory pathway in adipocytes involving miR-21a-3p, FGFR1, FGF21, and PPARγ that regulated adipocyte browning and participated in hyperglycemia-induced atrial fibrosis. Modulation of this signaling pathway may provide a therapeutic option for the prevention and treatment of atrial fibrosis or AF in DM.

Left ventricular geometry transition in hypertensive patients with heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFpEF) develops in response to hypertensive left ventricular (LV) hypertrophy and is associated with increased cardiovascular events. Although the progression to systolic heart failure is a known consequence of LV hypertrophy and HFpEF, few data are available on the LV geometry change and frequency of deterioration to systolic dysfunction in this population. METHODS AND RESULTS: We evaluated the baseline and follow-up characteristics in 680 patients with LV hypertrophy and HFpEF in this prospective cohort study. The primary endpoint was 5 year all-cause mortality. The changes of LV geometry and heart failure transition were analysed. Systolic dysfunction [left ventricular ejection fraction (LVEF) < 50%] occurred in 182 patients (26.8%) during a 5 year follow-up. Patients with LVEF deterioration were associated with a lower survival rate. Beta-blocker prescription was a protective factor for preserved LVEF. And concentric LV geometry shifted to eccentric hypertrophy was uncommon (10.6%) during a 5 year follow-up. CONCLUSIONS: A quarter of patients with hypertensive LV hypertrophy and HFpEF progresses to systolic dysfunction during a 5 year follow-up, which was accompanied by poor clinical outcomes. And beta-blocker therapy might play a protective role for preserved LVEF in this population.

Association of Circulating Irisin Levels and the Characteristics and Prognosis of Coronary Artery Disease.

BACKGROUND: Irisin is a new muscle factor discovered in recent years that shows a strong association with metabolic diseases. However, its role in coronary artery disease (CAD) is still controversial. We performed this study to determine the relationship of serum irisin with the characteristics and prognosis of CAD. MATERIALS AND METHODS: Patients with acute coronary syndrome (ACS) (n = 355), stable coronary artery disease (SCAD) (n = 162), nonobstructive coronary artery disease (NO-CAD) (n = 126) and normal coronary arteries (n = 109) were enrolled. An enzyme-linked immunosorbent assay kit was used to measure serum irisin concentrations. Major adverse cardiovascular events (MACEs) of patients with SCAD (n = 132) and ACS (n = 331) after percutaneous coronary intervention (PCI) were recorded during a 12-month follow-up. Receiver-operator characteristic (ROC) curve analysis was used to explore predictors of CAD. Kaplan-Meier survival analysis and the Cox proportional hazards regression model were used to explore the association between serum irisin levels and MACEs. RESULTS: Serum irisin levels in patients with ACS, SCAD, NO-CAD and normal coronary arteries were 196.62±72.05 ng/ml, 216.81±79.69 ng/ml, 245.26±77.92 ng/ml and 300.17±76.74 ng/ml, respectively (p<0.001). ROC curve analysis indicated that serum irisin concentrations were a valuable biomarker of coronary lesions (AUC=0.799), CAD (AUC=0.734) and ACS (AUC=0.681). Survival analysis demonstrated that patients with high irisin levels exhibited a higher event-free survival rate in both the SCAD and ACS groups after successful PCI. CONCLUSIONS: Serum irisin levels were significantly decreased in patients with CAD. Patients with ACS exhibited the lowest serum irisin levels. Furthermore, serum irisin levels were interrelated with prognosis in patients with CAD after PCI.

Characteristics, prognosis and treatment response in distinct phenogroups of heart failure with preserved ejection fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. We aimed to derive HFpEF phenotype-based groups based on clinical features using machine learning, and to compare clinical characteristics, outcomes and treatment response across the phenogroups. METHODS: We applied model-based clustering to 11 clinical and laboratory variables collected in 970 HFpEF patients. An additional 290 HFpEF patients was enrolled as a validation cohort. During 5-year follow-up, all-cause mortality was used as the primary endpoints, and composite endpoints (all-cause mortality or HF hospitalization) were set as the secondary endpoint. RESULTS: We identified three phenogroups, for which significant differences in the age and gender, the prevalence of concomitant ischaemic heart disease, atrial fibrillation and type 2 diabetes mellitus, the burden of B-type natriuretic peptide level and HF symptoms. Patients with phenogroup 3 had higher all-cause mortality or composite endpoints, whereas patients in phenogroup 1 had less adverse events after 5-year follow-up. Moreover, it was indicated that beta-blockers or angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) use was associated with a lower risk of all-cause mortality or composite endpoints in phenogroup 3, instead of the other phenogroups. This HFpEF phenogroup classification, including its ability to stratify risk, was successfully replicated in a prospective validation cohort. CONCLUSION: Machine-learning based clustering strategy is used to identify three distinct phenogroups of HFpEF that are characterized by significant differences in comorbidity burden, underlying cardiac abnormalities, and long-term prognosis. Beta-blockers or ACEI/ARB therapy is associated with a lower risk of adverse events in specific phenogroup.

Balloon Deflation Strategy during Primary Percutaneous Coronary Intervention in Acute ST-Segment Elevation Myocardial Infarction: A Randomized Controlled Clinical Trial and Numerical Simulation-Based Analysis.

BACKGROUND: Primary percutaneous coronary intervention (PCI) is the best available reperfusion strategy in patients with acute ST-segment elevation myocardial infarction (STEMI). However, PCI is associated with a serious problem known as no-reflow phenomenon, resulting in poor clinical and functional outcomes. This study aimed to compare the influences of different balloon deflation velocity on coronary flow and cardiovascular events during primary PCI in STEM as well as transient hemodynamic changes in in vitro experiments. Method and Results. 211 STEMI patients were randomly assigned to either a rapid or a slow balloon deflation group during stent deployment. The primary end point was coronary flow at the end of PCI procedure, and secondary end points included myocardial infarct size. Transient hemodynamic changes were evaluated through an in vitro experimental apparatus and a computer model. In clinical practice, the level of corrected TIMI frame count (cTFC) in slow balloon deflation after primary PCI was significantly lower than that of rapid balloon deflation, which was associated with smaller infarct size. Numerical simulations revealed that the rapid deflation led to a sharp acceleration of flow in the balloon-vessel gap and a concomitant abnormal rise in wall shear stress (WSS). CONCLUSION: This randomized study demonstrated that the slow balloon deflation during stent implantation improved coronary flow and reduced infarct size in reperfused STEMI. The change of flow in the balloon-vessel gap and WSS resulted from different balloon deflation velocity might be partly accounted for this results.

Association between long-term prescription of febuxostat and the progression of heart failure with preserved ejection fraction in patients with hypertension and asymptomatic hyperuricemia.

Both hypertension and hyperuricemia are closely associated with the morbidity and mortality of heart failure. This study was designed to evaluate the influences of long-term xanthine oxidase inhibitor (febuxostat) prescription on left ventricular hypertrophy (LVH), left ventricular (LV) diastolic function, and new-onset heart failure with preserved ejection fraction (HFpEF) in these patients. Using a propensity score matching of 1:2 ratio, this retrospective claims database study compared febuxosatat prescription (n = 96) and non-urate-lowering therapy (n = 192) in patients with hypertensive left ventricular hypertrophy (LVH) and asymptomatic hyperuricemia. With a follow-up of 36 months, febuxostat significantly decreased the level of serum uric acid as well as generated more prominent improvement in LVH and LV diastolic function. Besides, the new-onset symptomatic HFpEF occurred in 2 of 96 patients in febuxostat group and 13 of 192 patients in non-urate-lowering group (P = 0.091). No increased risk for major adverse cardiovascular events in patients prescribed with febuxostat was noted. In conclusion, long-term febuxostat exposure was associated with protective effects in terms of LVH or LV diastolic dysfunction in patients with hypertensive LVH and asymptomatic hyperuricemia. Febuxostat also displayed a trend for reduced risk of new-onset HFpEF in this population.

Characteristics and outcomes of transitions among heart failure categories: a prospective observational cohort study.

AIMS: Patients with heart failure (HF) are typically designated as having reduced, mid-range, or preserved ejection fraction (EF) (HFrEF, HFmrEF, or HFpEF, respectively) because of the importance of left ventricular EF (LVEF) on therapeutic decisions and prognosis. However, such designations are not necessarily static, as there are many transitions among the three HF phenotypes during follow-up. This prospective longitudinal cohort study sought to examine the HF transitions over time and their clinical characteristics, prognosis, and response to medical therapy. METHODS AND RESULTS: We identified 1920 patients from a prospective cohort with a primary diagnosis of HF between 1 January 2007 and 31 December 2012. The enrolled HF patients were re-classified into three groups on the basis of baseline and 1 year follow-up echocardiography: HF with improved EF (HFiEF), HF with deteriorated EF (HFdEF), and HF with unchanged EF (HFuEF). The primary outcome was 5 year all-cause mortality. According to 1 year follow-up echocardiography, 490 (25.5%) were diagnosed as HFiEF, 179 (9.3%) as HFdEF, and 1251 (65.2%) as HFuEF. Ischaemic heart disease was an independent predictor of HFdEF, and beta-blocker prescription was an independent predictor of HFiEF. During the 5 year follow-up, patients with HFdEF had higher mortality, whereas patients with HFiEF had lower mortality. After adjustment, HFiEF, compared with HFuEF, was associated with a 62.1% decreased risk for mortality. Finally, the use of beta-blockers was associated with improved prognosis of patients with HFiEF and HFuEF. CONCLUSIONS: In this cohort of patients with HF, LVEF is a dynamic factor related to coexisting conditions and drug therapy. HFiEF and HFdEF are distinct HF phenotypes with different clinical outcomes than other phenotypes.

Incidence of congenital heart diseases in Chinese children with non-syndromic congenital blepharoptosis: a prospective observational study of 1053 patients.

BACKGROUND: Congenital blepharoptosis (CBP) may be part of a large spectrum of birth defects presenting with other ocular or systemic conditions. Therefore, the aim of the study was to investigate the incidence of congenital heart diseases (CHD) in CBP children not associated with specific syndromes. METHODS: A total of 1053 Chinese children diagnosed with non-syndromic CBP were consecutively enrolled and their cardiac structure was evaluated by echocardiography. RESULTS: Forty children were identified with CHD. Twenty-four children had one type of structural malformation (simple CHD). Sixteen children had two or more types of structural malformation (complex CHD). CHD and complex CHD were more prevalent in patients with severe or bilateral ptosis. Multivariate analysis revealed that presence of severe ptosis and bilateral ptosis was independently associated with CHD occurrence. CONCLUSIONS: We found an increased frequency of CHD in CBP children, suggesting a clinical need for routine echocardiography evaluation in CBP, especially in children with severe or bilateral ptosis.