Single-cell profile reveals the landscape of cardiac immunity and identifies a cardio-protective Ym-1hi neutrophil in myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury (MIRI) is a major hindrance to the success of cardiac reperfusion therapy. Although increased neutrophil infiltration is a hallmark of MIRI, the subtypes and alterations of neutrophils in this process remain unclear. Here, we performed single-cell sequencing of cardiac CD45+ cells isolated from the murine myocardium subjected to MIRI at six-time points. We identified diverse types of infiltrating immune cells and their dynamic changes during MIRI. Cardiac neutrophils showed the most immediate response and largest changes and featured with functionally heterogeneous subpopulations, including Ccl3hi Neu and Ym-1hi Neu, which were increased at 6 h and 1 d after reperfusion, respectively. Ym-1hi Neu selectively expressed genes with protective effects and was, therefore, identified as a novel specific type of cardiac cell in the injured heart. Further analysis indicated that neutrophils and their subtypes orchestrated subsequent immune responses in the cardiac tissues, especially instructing the response of macrophages. The abundance of Ym-1hi Neu was closely correlated with the therapeutic efficacy of MIRI when neutrophils were specifically targeted by anti-Lymphocyte antigen 6 complex locus G6D (Ly6G) or anti-Intercellular cell adhesion molecule-1 (ICAM-1) neutralizing antibodies. In addition, a neutrophil subtype with the same phenotype as Ym-1hi Neu was detected in clinical samples and correlated with prognosis. Ym-1 inhibition exacerbated myocardial injury, whereas Ym-1 supplementation significantly ameliorated injury in MIRI mice, which was attributed to the tilt of Ym-1 on the polarization of macrophages toward the repair phenotype in myocardial tissue. Overall, our findings reveal the anti-inflammatory phenotype of Ym-1hi Neu and highlight its critical role in myocardial protection during the early stages of MIRI.

No evidence of coronary plaque stabilization by allopurinol in patients with acute coronary syndrome.

BACKGROUND: Allopurinol, a xanthine inhibitor that lowers uric acid concentration, has been proven to reduce inflammation and oxidative stress in patients with cardiovascular disease. However, it is unknown whether these beneficial effects translate into favorable plaque modification in acute coronary syndromes (ACS). This study aimed to investigate whether allopurinol could improve coronary plaque stabilization using coronary computed tomography angiography (CCTA). METHODS: This was a prospective, single-center, randomized, double-blind clinical trial began in March 2019. A total of 162 ACS patients aged 18-80 years with a blood level of high-sensitivity C-reactive protein (hsCRP) â€‹> â€‹2 â€‹mg/L were included. The subjects were randomly assigned in a 1:1 ratio to receive either allopurinol sustained-release capsules (at a dose of 0.25 â€‹g once daily) or placebo for 12 months. The plaque analysis was performed at CCTA. The primary efficacy endpoint was the change in low-attenuation plaque volume (LAPV) from baseline to the 12-month follow-up. RESULTS: Among 162 patients, 54 in allopurinol group and 51 in placebo group completed the study. The median follow-up duration was 14 months in both groups. Compared with placebo, allopurinol therapy did not significantly alter LAPV (-13.4 â€‹± â€‹3.7 â€‹% vs. -17.8 â€‹± â€‹3.6 â€‹%, p â€‹= â€‹0.390), intermediate attenuation plaque volume (-16.1 â€‹± â€‹3.0 â€‹% vs. -16.2 â€‹± â€‹2.9 â€‹%, p â€‹= â€‹0.992), dense calcified plaque volume (12.2 â€‹± â€‹13.7 â€‹% vs. 9.7 â€‹± â€‹13.0 â€‹%, p â€‹= â€‹0.894), total atheroma volume (-15.2 â€‹± â€‹3.2 â€‹% vs. -16.4 â€‹± â€‹3.1 â€‹%, p â€‹= â€‹0.785), remodeling index (2.0 â€‹± â€‹3.9 â€‹% vs. 5.4 â€‹± â€‹3.8 â€‹%, p â€‹= â€‹0.536) or hsCRP levels (-73.6 [-91.6-17.9] % vs. -81.2 [-95.4-47.7] %, p â€‹= â€‹0.286). CONCLUSIONS: Our findings suggest that allopurinol does not improve atherosclerotic plaque stability or inflammation in ACS.

Case report: A rare case of left ventricular noncompaction in two Chinese siblings with becker muscular dystrophy caused by deletion of exons 10 to 12 in the DMD gene.

Background: Becker muscular dystrophy (BMD) is an inherited X-linked recessive condition resulting from mutations of the DMD gene encoding dystrophin. Left ventricular noncompaction (LVNC) is a rare cardiomyopathy morphologically characterized by abnormal myocardial trabeculae and deep recesses in the left ventricle. LVNC in BMD patients has only rarely been reported. Case report: In the present study, we identified a deletion mutation in exons 10 to 12 (EX10_12 del) of the DMD gene (reference sequence NM_004006.2) in two Chinese siblings with BMD and LVNC by high throughput targeted next-generation sequencing (NGS) and quantitative polymerase chain reaction (qPCR). The proband was a 22-year-old man admitted with dyspnea, abdominal distention, and polyserositis. It is noteworthy that both the proband and his younger brother manifested progressive muscular atrophy and creatine kinase (CK) elevation. Light and electron microscopy examination of muscle biopsies showed the typical features of dystrophinopathies. Cardiac magnetic resonance imaging and echocardiography demonstrated that both brothers had an enlarged left ventricle, LVNC, and reduced left ventricular ejection fraction. Finally, the proband underwent heart transplantation at age 26 with an event-free follow-up over 4 years post-transplantation. Conclusion: This case further enriches our knowledge of the symptoms, genotype, cardiac performance, management, and prognosis of BMD patients complicated by LVNC. It is recommended that early comprehensive cardiac evaluation should be considered for patients with BMD to exclude LVNC, as this may have a significant impact on their prognosis.

Berberine plays a cardioprotective role by inhibiting macrophage Wnt5a/ß-catenin pathway in the myocardium of mice after myocardial infarction.

Myocardial infarction (MI) is one of the diseases with high fatality rate. Berberine (BBR) is a monomer compound with various biological functions. And some studies have confirmed that BBR plays an important role in alleviating cardiomyocyte injury after MI. However, the specific mechanism is unclear. In this study, we induced a model of MI by ligation of the left anterior descending coronary artery and we surprisingly found that BBR significantly improved ventricular remodeling, with a minor inflammatory and oxidative stress injury, and stronger angiogenesis. Moreover, BBR inhibited the secretion of Wnt5a/ß-catenin pathway in macrophages after MI, thus promoting the differentiation of macrophages into M2 type. In summary, BBR effectively improved cardiac function of mice after MI, and the potential protective mechanism was associated with the regulation of inflammatory responses and the inhibition of macrophage Wnt5a/ß-catenin pathway in the infarcted heart tissues. Importantly, these findings supported BBR as an effective cardioprotective drug after MI.

Case report: Spontaneous closure of ventricular pseudoaneurysm post-acute myocardial infarction with non-surgical therapy.

Left ventricle (LV) pseudoaneurysm is a rare disorder post-acute myocardial infarction (AMI). Resection or closure of the pseudoaneurysm by surgery is recommended due to the high propensity of pseudoaneurysm rupture while surgery has also high risks. Conservative therapy could be acceptable in small pseudoaneurysms or patients with high surgical risks. Nevertheless, the risk evaluation and grasp of indication are not clear. This case reported an acute cyst-like LV pseudoaneurysm formation post-AMI-induced myocardial free wall rupture (MFWR), and the patient recovered with spontaneous closure of the fissure and shrinkage of the LV pseudoaneurysm through non-surgical therapy. Based on the observations in the echocardiogram, we proposed that intermittent closing of the fissure and interruption of the blood flow between the LV and the pseudoaneurysm due to LV contraction alleviated stress change on the pseudoaneurysm. The narrow fissure, small pseudoaneurysm, and intermittently interrupted blood flow that benefit fissure healing and pseudoaneurysm stabilization could indicate the prognosis of this patient. Drugs like ß-blocker that decreased the stress on the pseudoaneurysm also led to the risk reduction of pseudoaneurysm rupture. To our knowledge, this is the first case that reports a spontaneous closure of LV pseudoaneurysm. The size of the fissure and the pseudoaneurysm, as well as the corresponding hemodynamic state, could be valuable to evaluate the risk and prognosis of the pseudoaneurysm. Optimized medical management was also helpful to pseudoaneurysm stabilization.

Systematic Immune-Inflammation Index Predicts Embolic Events in Infective Endocarditis.

Infective endocarditis (IE) is a life-threatening disease with embolisms occurring in 20%-50% of cases. We aimed to evaluate the value of the systemic immune-inflammation index (SII) in predicting embolic events (EEs) in patients with infective endocarditis.A total of 186 patients diagnosed with definite IE, who admitted to the Union Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology, were retrospectively identified from November 2011 to March 2019.The median (interquartile) age of the patients was 46 (32-57) years. Viridans group streptococci were the most common microorganism identified from blood culture (24.7%). The most frequent complication was heart failure (64.2%), followed by EEs (30.2%). Patients complicated with EEs presented a significantly higher SII than those without EEs (1605.38 versus 1039.61, P = 0.001). SII had an area under the curve (AUC) value for EEs of 0.661 (95% CI: 0.575-0.747, P = 0.001), which predicted the presence of EEs with a sensitivity of 42.6% and specificity of 86.3%. Multivariate logistic regression analysis revealed that SII (OR = 6.925; 95% CI: 1.035-46.318, P = 0.046) was an independent predictor of EEs in IE patients.We demonstrated that a high level of SII is associated with a higher likelihood of EEs. The SII may be a promising predictor for EEs in patients with IE.

Case Report: Glucocorticoid Effect Observation in a Ureteral Urothelial Cancer Patient With ICI-Associated Myocarditis and Multiple Organ Injuries.

Immune checkpoint inhibitor (ICI)-associated immune-related adverse events (irAEs) are becoming important safety issues worthy of attention despite the exciting therapeutic prospects. The growing development of new ICIs also brings new cases of irAEs, raising more challenges to clinicians. Cardiac injury is rare but life-threatening among diverse organ injuries, and effective interventions are critical for patients. Here, we report a novel programmed cell death protein-1 (PD-1) inhibitor tislelizumab-associated severe myocarditis and myositis accompanied by liver and kidney damage in a ureteral urothelial cancer patient, who was firstly treated by cardiologists because of cardiac symptoms. Due to the lack of experience about ICI-associated irAEs, an initial low-dose (0.5 mg/kg/day) and short-term methylprednisolone therapy was used and found to be ineffective and risky to the patient; then, steroid therapy was modulated to a higher dose (1.5 mg/kg/day) with prolonged time course, and improvement of patient symptoms and laboratory markers were observed quickly and persistently. The patient did not show adverse events under this steroid dosage. This case reports a rare tislelizumab-related myocarditis and multiple organ injuries, which provides valuable experience to cardiologists like us. Early recognition of ICI-associated myocarditis and sufficient dosage and time course of glucocorticoid therapy are critical for severe cases. High-quality clinical evidence about the precise diagnosis and therapy in ICI-associated myocarditis and other organ injuries are necessary to guide our clinical works.

18ß-Glycyrrhetinic Acid Improves Cardiac Diastolic Function by Attenuating Intracellular Calcium Overload.

Ranolazine, a late sodium current inhibitor, has been demonstrated to be effective on heart failure. 18ß-glycyrrhetinic acid (18ß-GA) has the similar inhibitory effect on late sodium currents. However, its effect on diastolic function is still unknown. This study aimed to determine whether 18ß-GA can improve the diastolic function and to explore the underlying mechanisms. Eighty male Sprague Dawley (SD) rats of Langendorff model were randomly divided into the following groups: group A, normal cardiac perfusion group; group B, ischemia-reperfusion group; group C, ischemia-reperfusion with anemoniasulcata toxin II (ATX-II); group D, ranolazine group; and group E, 18ß-GA group with four different concentrations. Furthermore, a pressure-overloaded rat model induced by trans-aortic constriction (TAC) was established. Echocardiography and hemodynamics were used to evaluate diastolic function at 14th day after TAC. Changes of free intracellular calcium (Ca2+) concentration was indirectly detected by laser scanning confocal microscope to confirm the inhibition of late sodium currents. With the intervention of ATX-II on ischemia reperfusion injury group, 5 µmol/L ranolazine, and 5, 10, 20, 40 µmol/L 18ß-GA could improve ATX-II-induced cardiac diastolic dysfunction. 630 mg/kg glycyrrhizin tablets could improve cardiac diastolic function in the pressure-overloaded rats. 18ß-GA and ranolazine had similar effects on reducing the free calcium in cardiomyocytes. The study demonstrates that 18ß-GA and glycyrrhizin could improve diastolic dysfunction induced by ischemia-reperfusion injury in Langendorff-perfused rat hearts and pressure-overloaded rats. The mechanism may be attributed to the inhibition of enhanced late sodium currents.

GDF-15 is associated with thrombus burden in patients with deep venous thrombosis.

INTRODUCTION: Growth differentiation factor-15 (GDF-15) has been identified as a predictor in cardiovascular diseases and acute pulmonary embolism. However, the association of GDF-15 and deep venous thrombosis (DVT) remains unclear. This study aimed to investigate levels of GDF-15 in patients with DVT, and determine its association with the thrombus burden. MATERIALS AND METHODS: 72 newly diagnosed DVT patients and 30 healthy volunteers were enrolled, and the levels of plasma GDF-15 were detected. To explore the relationship between GDF-15 and thrombus severity, we analyzed the thrombus burden and the association with pulmonary embolism of DVT patients. In vitro, the effect of GDF-15 on platelet aggregation and thrombin/antithrombin activity were investigated. RESULTS: We found that the mean levels of plasma GDF-15 in DVT patients were significantly higher than those in healthy controls (1448.78 ± 61.98 pg/ml VS 805.70 ± 112.95 pg/ml, P < 0.001). Furthermore, GDF-15 showed an increase with more venous segments with thrombus (P < 0.001), and the patients with higher levels of GDF-15 and more thrombus segments showed higher scores of Wells-PE and Geneva and increased incidence of pulmonary embolism (P < 0.05). In vitro, we confirmed that GDF-15 significantly reduced platelet aggregation induced by ADP and the effect was concentration-dependent (P < 0.001). However, GDF-15 showed no direct effect on thrombin and anti-thrombin activity. CONCLUSIONS: Increased GDF-15 level was associated with more thrombus severity of DVT patients and GDF-15 could inhibit platelet aggregation induced by ADP in vitro. These findings suggest that GDF-15 might not only be an indicator for thrombus severity but also be a potential treatment target in DVT.

Global Functional Network Connectivity Disturbances in Parkinson's Disease with Mild Cognitive Impairment by Resting-State Functional MRI.

Examining the spontaneous BOLD activity to understand the neural mechanism of Parkinson's disease (PD) with mild cognitive impairment (MCI) is a focus in resting-state functional MRI (rs-fMRI) studies. This study aimed to investigate the alteration of brain functional connectivity in PD with MCI in a systematical way at two levels: functional connectivity analysis within resting state networks (RSNs) and functional network connectivity (FNC) analysis. Using group independent component analysis (ICA) on rs-fMRI data acquired from 30 participants (14 healthy controls and 16 PD patients with MCI), 16 RSNs were identified, and functional connectivity analysis within the RSNs and FNC analysis were carried out between groups. Compared to controls, patients with PD showed decreased functional connectivity within putamen network, thalamus network, cerebellar network, attention network, and self-referential network, and increased functional connectivity within execution network. Globally disturbed, mostly increased functional connectivity of FNC was observed in PD group, and insular network and execution network were the dominant network with extensively increased functional connectivity with other RSNs. Cerebellar network showed decreased functional connectivity with caudate network, insular network, and self-referential network. In general, decreased functional connectivity within RSNs and globally disturbed, mostly increased functional connectivity of FNC may be characteristics of PD. Increased functional connectivity within execution network may be an early marker of PD. The multi-perspective study based on RSNs may be a valuable means to assess functional changes corresponding to specific RSN, contributing to the understanding of the neural mechanism of PD.

Intravenous Immunoglobulin Therapy for Acute Myocarditis in Children and Adults.

The efficacy of intravenous immunoglobulin (IVIG) in the treatment of acute myocarditis remains controversial. The aim of this study was to conduct a meta-analysis to assess the efficacy of IVIG in children and adults with acute myocarditis.We searched PubMed, Scopus, Embase, Medline, the Cochrane Library, Google Scholar, and the ClinicalTrials.gov website. Eligible studies were clinical trials of patients with acute myocarditis who received IVIG therapy. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the outcomes.Thirteen studies with 1534 cases were incorporated into our meta-analysis. Pooled results showed that IVIG therapy significantly reduced in-hospital mortality (OR: 0.44, 95% CI 0.17 to 0.71, P < 0.001) and improved the left ventricular ejection fraction (LVEF) (OR: 1.73, 95% CI 1.34 to 2.13, P < 0.001) in acute myocarditis patients. Furthermore, patients with acute fulminant myocarditis (AFM) exhibited a significantly higher survival rate (OR: 2.80, 95% CI 1.16 to 6.77, P = 0.022) in the IVIG group.IVIG therapy can not only result in lower in-hospital mortality and superior recovery of left ventricular function in patients with acute myocarditis, but also increase the survival rate of AFM patients. The present study provides some supportive evidence for IVIG therapy in acute myocarditis patients.

Relaxin-2 improves diastolic function of pressure-overloaded rats via phospholamban by activating Akt.

BACKGROUND: Relaxin is a peptide hormone which has been demonstrated to be safe and has a therapeutic effect on acute heart failure in clinic trials. However, its effect on diastolic function is still unknown. The aims of the study were to determine whether relaxin could improve the diastolic function in pressure-overloaded rat model and to analyze potential mechanisms. METHODS AND RESULTS: In the present study, a pressure-overloaded rat model induced by transaortic constriction (TAC) was established. Four weeks after TAC, echocardiography was performed and then all the rat models were randomly divided into 3 groups: models without intramyocardial injection (TAC), with intramyocardial injection of empty adenoviral vector (TAC+GFP) and adenoviral vector overexpression relaxin-2 gene (TAC+RLN2). A sham group was also included. Twelve days after intramyocardial injection, echocardiography and hemodynamics were carried out to evaluate diastolic function in sham, TAC, TAC+GFP and TAC+RLN2 groups. Then hearts were harvested for subsequent examinations. The results indicated that relaxin-2 had ameliorated diastolic function in the pressure-overloaded rats. Compared with the TAC and TAC+GFP groups, the relaxin-2 gene transfer increased phosphorylation of Akt at both the Ser473 and Thr308 sites. Meanwhile, it increased the Ser16 and Thr17- phosphorylation levels of phospholamban (PLB). Furthermore, SERCA2 activity was enhanced in the TAC+RLN2 group more than in the TAC and TAC+GFP groups. CONCLUSIONS: These results demonstrated that relaxin-2 gene therapy improved diastolic function in pressure-overloaded rats. The potential mechanism may be that relaxin-2 gene transfer enhances SERCA2 activity in hearts by increasing phospholamban phosphorylation through nuclear-targeted Akt phosphorylation.

Elevated soluble ST2 and depression increased the risk of all-cause mortality and hospitalization in patients with heart failure.

This study aimed to assess the predictive effect of soluble ST2 (sST2) and depressive symptoms in patients with heart failure (HF) and to determine whether the prognosis of HF patients with preserved ejection fraction (HFpEF) differs from those with reduced ejection fraction (HFrEF). A cohort of 233 HF patients was followed for 1 year. Depressive symptoms were evaluated by the Hospital Anxiety and Depression Scale. The primary endpoint was all-cause mortality and HF-related hospitalization. For the analysis of survival, the left ventricular ejection fraction (LVEF) cut-offs for defining HFpEF were set at 50%, 45%, and 40%, respectively. With increasing LVEF, levels of sST2 were gradually decreased (45.2 ng/mL, 35.8 ng/mL, and 32.1 ng/mL in patients with LVEF ≤ 40%, 41% to 49%, and ≥ 50%, respectively, P for trend < 0.001), as well as the prevalence of depressive symptoms (35.4%, 33.3%, and 20.4%, respectively, P for trend = 0.022). After 1-year follow-up, 128 patients (54.9%) achieved the primary endpoint and 47 patients (20.2%) died. Depressive symptoms were independent risk factors of all-cause mortality and HF-related hospitalization. The combined presence of elevated sST2 (> 36.0 ng/mL) and depressive symptoms was associated with a 4.9-fold increased risk of the primary endpoint. Regardless of LVEF cut-offs, the associated risk of adverse outcomes in HFpEF was as high as in HFrEF after adjustment for significant risk factors including sST2 and N-terminal pro-brain natriuretic peptide. In conclusion, depressive symptoms provided additional prognostic information to that of sST2 in HF patients. The prognosis of HFpEF patients was similar to that of HFrEF patients.

Left atrial enlargement in the early stage of hypertensive heart disease: a common but ignored condition.

How to identify the early signs of hypertensive heart disease is the key to block or reverse the process of heart failure. The aim of this study was to evaluate the predictive value of left atrial (LA) enlargement in the early stage of hypertensive heart disease and to explore the correlations between LA enlargement and heart failure with normal ejection fraction (HFnEF), as well as the metabolic syndrome (MetS). Baseline clinical characteristics, biochemical indices, electrocardiographic and echocardiographic data were collected from 341 consecutive patients with essential hypertension. Among those patients, LA enlargement was more frequently presented than LV enlargement (57.2% vs 17.9%). Compared with patients without HFnEF, the prevalence of LA enlargement was higher in patients with HFnEF (82.9% vs 49.0%, P<.0001). From grade 2 to grade 3 hypertension, LA size was significantly larger in patients with MetS (P<.01) than those without. Multivariate linear regression analyses showed that age, body mass index, waist circumference, triglyceride level, and left ventricular diameter were independent predictors of LA enlargement. The simple measurement for identification of LA enlargement potentially allows early recognition of those patients at risk for heart failure, particularly among patients with MetS.

Hepatocyte growth factor gene-modified bone marrow-derived mesenchymal stem cells transplantation promotes angiogenesis in a rat model of hindlimb ischemia.

Angiogenic gene therapy and cell-based therapy for peripheral arterial disease(PAD) have been studied intensively currently. This study aimed to investigate whether combining mesenchymal stem cells(MSCs) transplantation with ex vivo human hepatocyte growth factor(HGF) gene transfer was more therapeutically efficient than the MSCs therapy alone in a rat model of hindlimb ischemia. One week after establishing hindlimb ischemia models, Sprague-Dawley(SD) rats were randomized to receive HGF gene-modified MSCs transplantation(HGF-MSC group), untreated MSCs transplantation (MSC group), or PBS injection(PBS group), respectively. Three weeks after injection, angiogenesis was significantly induced by both MSCs and HGF-MSCs transplantation, and capillary density was the highest in the HGF-MSC group. The number of transplanted cell-derived endothelial cells was greater in HGF-MSC group than in MSC group after one week treatment. The expression of angiogenic cytokines such as HGF and VEGF in local ischemic muscles was more abundant in HGF-MSC group than in the other two groups. In vitro, the conditioned media obtained from HGF-MSCs cultures exerted proproliferative and promigratory effects on endothelial cells. It is concluded that HGF gene-modified MSCs transplantation therapy may induce more potent angiogenesis than the MSCs therapy alone. Engraftment of MSCs combined with angiogenic gene delivery may be a promising therapeutic strategy for the treatment of severe PAD.

Diagnosis of heart failure with preserved ejection fraction: which parameters and diagnostic strategies are more valuable?

AIMS: There are no unified criteria for diagnosing heart failure with preserved ejection fraction (HFpEF). The aim of this study was to evaluate the present main diagnostic criteria and to discover which parameters and strategies are more valuable. METHODS AND RESULTS: Echocardiographic data and plasma N-terminal pro-brain natriuretic peptide  levels were assessed in a derivation cohort (n= 236) and a validation cohort (n= 98). Both cohorts included normal controls, patients with hypertensive heart disease without heart failure and patients with HFpEF. In the derivation cohort, the ratio of early mitral inflow velocity to tissue Doppler velocity at lateral mitral annulus (lateral E/e'≥12), left atrial volume index (LAVI≥34 mL/m(2)), and the difference between duration of reversed pulmonary vein atrial systole flow and duration of mitral A wave flow (Ard-Ad>30 ms) had the greatest diagnostic value among all the single parameters. A brief strategy that consisted of either: (i) lateral E/e'≥12; or (ii) 12>lateral E/e'≥8, with either LAVI≥34 mL/m(2) or Ard-Ad>30 ms, provided good diagnostic accuracy for identifying diastolic dysfunction in HFpEF, with a sensitivity of 77% and specificity of 81%. These observations were confirmed in the validation cohort. CONCLUSION: Echocardiographic parameters including lateral E/e', LAVI, and Ard-Ad have the greatest value in diagnosing HFpEF. A brief strategy that included these three parameters had great diagnostic value and would be simple to use in clinic practice.