Background Percutaneous mechanical circulatory support (pMCS) alleviates cardiac workload and improves heart function, making it the preferred treatment for fulminant myocarditis (FM). However, the impact of pMCS on prognosis and long-term cardiac function in FM patients is still debated. Methods This retrospective study examined the demographics, laboratory tests, medications, and echocardiographic evaluations of patients with FM who required pMCS at our center from 2016 to 2022. Patients were categorized into two groups based on their pMCS requirements: those treated exclusively with intra-aortic balloon pump (IABP) therapy (IABP group) and those who required both veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and IABP (ECMO+IABP group). The primary outcomes were cardiac-related mortality and rehospitalization due to myocarditis. Secondary outcomes included all-cause mortality and long-term cardiac function and structure. Left ventricular (LV) function and structure were evaluated using two-dimensional volume and speckle-tracking strain echocardiography. Measurements were collected at admission, discharge, and at 1, 6, and 12 months post-discharge, with annual follow-ups thereafter. Results In this study, which included 87 enrolled patients, it was observed that those in the ECMO+IABP group exhibited higher heart rates, lower systolic blood pressure, and required longer durations and higher doses of glucocorticoids and intravenous immunoglobulin, in addition to a prolonged duration of IABP support. There were no significant differences between the two groups regarding the incidences of primary and secondary composite endpoints. Multivariable Cox regression analysis identified age and global longitudinal strain (GLS) at discharge as independent predictors of secondary composite endpoints. Age was positively correlated with the secondary outcome event (HR = 1.058, 95% CI [1.001, 1.117], P = 0.046), whereas the absolute value of GLS was negatively correlated with the secondary outcome event (HR = 0.739, 95% CI [0.556, 0.983], P = 0.038). Conclusions This study indicates a comparable and favorable prognosis for patients with FM receiving pMCS in time, regardless of required V-A ECMO, while GLS at discharge may be a tool to predict long-term prognosis.

Background:Elevated serum high-sensitivity cardiac troponin (hs-cTn) levels are commonly observed in patients with fulminant myocarditis (FM) after the acute phase. This study aims to evaluate the relationship between elevated hs-cTnI levels at 30-day post-discharge and long-term cardiac structure and function. Methods:This study is a retrospective cohort study that selected FM patients hospitalized at Tongji Hospital in Wuhan from April 2016 to December 2022. All patients underwent serial monitoring of hs-cTnI levels. Patients were stratified into two groups based on hs-cTnI levels at 30 days post-discharge: the normal hs-cTnI (N-cTnI) group and the high hs-cTnI (H-cTnI) group. Left ventricular (LV) function and structure were assessed using 2-dimensional volume and speckle tracking strain echocardiography. Measurements were obtained at admission, discharge, and 6 months, 12 months, and annually thereafter post-discharge. Results:Among 95 patients with analysable echocardiographic data (median age: 33 years; 42.11 % male), the N-cTnI group demonstrated significantly higher proportions of patients meeting cardiac function criteria during follow-up compared to the H-cTnI group: LV ejection fraction (LVEF) > 50 % (95 % vs. 72 %; P = 0.003), global longitudinal strain (GLS) > 16 % (68 % vs. 36 %; P = 0.002), and LV end-diastolic dimension < 5 cm (86 % vs. 65 %; P = 0.020). Given that the primary composite endpoint occurred in only 5 patients, statistical analyses focused on secondary composite endpoints. The incidence of secondary composite endpoints was significantly higher in the H-cTnI group than in the N-cTnI group (61.91 % vs. 16.98 %; P < 0.001). Multivariable Cox regression identified elevated hs-cTnI at 30 days post-discharge (HR: 5.365; 95 % CI: 1.876-15.344; P = 0.002) and LV-GLS at discharge (HR: 0.844; 95 % CI: 0.732-0.974; P = 0.021) as independent predictors of secondary composite endpoints. Conclusion:Delayed normalization of hs-cTnI after 30 days post-discharge may predict long-term deterioration of cardiac function and structural remodeling in patients with FM.

Traditional ultrasound methods, particularly cardiac echocardiography, depend predominantly on evidence-based decision trees and risk-scoring systems to guide and standardise clinical decision-making. Although these approaches demonstrate some effectiveness, their inherent rigidity and failure to address non-linear interactions lead to inadequate consideration of individual variability, thereby compromising diagnostic accuracy and consistency. Furthermore, these conventional techniques are vulnerable to human bias, which increases the risk of misdiagnosis. In contrast, artificial intelligence (AI)-based analytical strategies substantially overcome these limitations using machine and deep learning methodologies. Furthermore, AI can autonomously annotate, measure, and evaluate cardiac function, significantly minimising human error, while enhancing diagnostic precision and reliability. In addition, AI can quickly process extensive volumes of imaging data and efficiently quantify cardiovascular pathological features, thereby improving the efficacy and accuracy of cardiovascular disease diagnosis. AI is widely applied in various areas of cardiac echocardiography, including image classification, disease screening, and automated measurements. Given the increasing integration of AI into cardiac echocardiography practices, we present a comprehensive review of the advantages of AI strategies and their practical applications, aiming to provide profound insights that may help promote automated intelligent analysis of echocardiography.

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

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

Background: Acute myocardial infarction (AMI) carries a high short-term risk of death, even after percutaneous coronary intervention (PCI). Glucose variability (GV), measured by the glucose coefficient of variation (GluCV), is a potential risk factor for adverse outcomes. This study investigates GluCV's predictive value for in-hospital mortality in AMI patients undergoing PCI. Method: This study involved 2325 AMI patients who were admitted to the ICU and underwent PCI from the MIMIC-IV database. Patients were categorized into quartiles based on GluCV: <0.13, 0.13-0.20, 0.20-0.29, and >= 0.29. Multivariable logistic regression and Restricted cubic spline (RCS) analysis were employed to analyze the relationship between GluCV and in-hospital mortality. Mediation analysis was used to evaluate the role of GluCV in the relationship between disease complexity and severity. Results: Among the 2325 patients, 203 (8.7 %) died during hospitalization. Higher GluCV was associated with increased in-hospital mortality. Adjusted odds ratios for mortality were 1.35 (95 % CI: 0.71-2.55), 1.91 (95 % CI: 1.04-3.51), and 3.32 (95 % CI: 1.83-6.02) for the second, third, and fourth groups, respectively. RCS analysis indicated a linear relationship between Log GluCV and mortality risk, with each 1 SD increase in Log GluCV associated with a 1.70-fold increase in mortality. Subgroup analysis showed a stronger relationship between GluCV and mortality in patients younger than 70. Mediation analysis indicated that GluCV partially mediates the effect of comorbidities on organ dysfunction. Conclusions: GluCV is an important predictor of in-hospital mortality in AMI patients undergoing PCI. Managing GV to minimize fluctuations may improve patient prognosis.

BACKGROUND:Metastasis of malignant tumors to the cardiac endocardium is rare and mainly involves the right side of the heart. It is extremely rare to involve the left cardiac endocardium, especially when there is neither pulmonary metastasis nor primary lung cancer, which we call "isolated" left cardiac endocardium metastasis in this paper. Few such cases previously reported in the literature were not screened for patent foramen ovale (PFO). CASE PRESENTATION:This article reports a case of a young woman with a history of surgery for cervical cancer, who was transferred to our hospital with a suspected diagnosis of PFO after recent recurrent multiple cerebral infarctions. On admission, transthoracic echocardiography revealed multiple stringy vegetations in the left ventricle, which were subsequently removed surgically, with intraoperative confirmation of a patent foramen ovale and closure of it simultaneously. According to her medical history and pathological results, she was diagnosed with left ventricular metastasis of cervical cancer, a rare case of isolated left heart endocardium metastasis without previous pulmonary metastasis, presumably through the patent foramen ovale. CONCLUSION:PFO may play an important role in the process of isolated left heart endocardium metastasis in patients with distant malignancies and paradoxical embolism. Screening for PFO in high-risk patients may have significant clinical significance.

Fulminant myocarditis (FM) is characterized by rapid cardiac deterioration often instigated by an inflammatory cytokine storm. The kallikrein-kinin system (KKS) is a metabolic cascade known for releasing vasoactive kinins, such as bradykinin-related peptides, possessing diverse pharmacological activities that include inflammation, regulation of vascular permeability, endothelial barrier dysfunction, and blood pressure modulation. The type 1 and type 2 bradykinin receptors (B1R and B2R), integral components of the KKS system, mediate the primary biological effects of kinin peptides. This review aims to offer a comprehensive overview of the primary mechanisms of the KKS in FM, including an examination of the structural components, regulatory activation, and downstream signaling pathways of the KKS. Furthermore, it explores the involvement of the tissue kallikrein/B1R/inducible nitric oxide synthase (TK/B1R/iNOS) pathway in myocyte dysfunction, modulation of the immune response, and preservation of endothelial barrier integrity. The potential therapeutic advances targeting the inhibition of the KKS in managing FM will be discussed, providing valuable insights for the development of clinical treatment strategies.

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

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

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

Review Association between Cardiopulmonary Exercise Test and Severity of Obstructive Sleep Apnea Syndrome Jianyu Wang 1,2, * , Shishi Zhang 2, Luying Jiang 3, Chunran Zhang 3, and Houjuan Zuo 2 1 Tianyou Hospital, Wuhan University of Science and TechnologyWuhan430064China 2 Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan430030China 3 The 3rd Department of Cardiology, The First Affiliated Hospital of The Medical College, Shihezi UniversityShihezi832008China * Correspondence: Wangjianyu1003@163.com Received: 17 April 2023 Accepted: 6 June 2023 Published: 27 December 2023 Abstract: Obstructive sleep apnea syndrome (OSAS) is becoming widespread, especially in people with obesity. As it is usually measured by polysomnography (PSG), the role of cardiopulmonary exercise test (CPET), a new exercise capacity test, has not attracted enough attention in OSAS research. In this article, we explore the relationship between CPET results and patients with OSAS. 68 individuals were recruited and divided into three groups: negative/mild group (n = 22, apnea hypopnea index (AHI) < 15), moderate group (n = 22, 15 ≤ AHI < 30) and severe group (n = 24, AHI ≥ 30). Clinical parameters, cardiopulmonary exercise test (CPET) indexes, and apnea hypopnea index (AHI) were compared among the three groups. A multivariate analysis was carried out to assess which factors determine the index of AHI. The ANOVA analyses were used to evaluate the difference among the three groups. Receiver operating characteristic analyses were chosen to detect the prediction efficiency of the CPET index for AHI. The predictive power of using the CPET index (VO2/kg peak) combined with the body mass index (BMI) of patients in the detection of AHI was significantly better when compared with using the CPET index only. There was a notable correlation between VO2 and the index of AHI (r = 0.249, P = 0.04). Also, the CPET data (VO2/kg peak) combined with the BMI of patients has powerful predictive value for the severity of OSAS in patients. It is expected to be a promising way to predict the severity of OSAS in the future. Our study provides a new strategy for predicting whether a patient is in the early phase OSAS.

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

Background:To determine the effects of inspiratory muscle training (IMT) alone on inspiratory muscle strength and endurance, pulmonary function, pulmonary complications, and length of hospital stay in patients undergoing coronary artery bypass graft surgery (CABG). Methods:We conducted a literature search across databases (Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily; Ovid Embase; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus) from inception to December 2021. The eligibility criteria were randomized controlled trials that investigated the effects of IMT versus usual care or sham IMT in patients undergoing CABG. Results:A total of 12 randomized clinical trials with 918 patients were included in the meta-analysis. Postoperative IMT was associated with improved maximal inspiratory pressure (MIP), maximum inspiratory pressure (PImax), and six-minute walking test (6MWT) and with a decrease in length of hospital stay (LOS). For preoperative IMT, there was statistical significance between intervention and MIP, PImax, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), postoperative pulmonary complications (PPCs), and LOS. Pre- and postoperative IMT resulted in improvements in MIP. Conclusions:Isolated IMT in patients who underwent CABG improved their inspiratory muscle strength and endurance, pulmonary function, and 6MWT and helped decrease postoperative pulmonary complications and the length of hospital stay.

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

Although type 2 diabetes mellitus (T2DM) individuals easily develop three‐vessel disease (3VD) coronary artery disease (CAD), there is very little information available about their left ventricle (LV) functions. The purpose of this study is to evaluate the LV function using two‐dimensional speckle tracking echocardiography (2‐D STE) in T2DM patients with 3VD.

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