Contemporary spectrum, characteristics, and outcomes of adult patients with rheumatic valvular disease in China: Insights from the China-VHD study.

Background: Rheumatic valvular disease (RVD) represents a significant health concern in developing countries, yet a scarcity of detailed data exists. This study conducts a comprehensive examination of RVD patients in China, exploring aspects of the disease's spectrum, characteristics, investigation, management, and outcomes. Methods: The China Valvular Heart Disease (China-VHD) study, a nationwide, multicenter, prospective observational study, enrolled 13,917 adults with moderate-to-severe valvular heart disease from April to June 2018. Among these, 2402 patients with native RVD (19.7% of native VHD patients) were analyzed. Results: Among the RVD patients, the median age was 57 years (interquartile range 50-65), with 82.5% falling within the 40-70 age range; females were notably predominant (63.9%). Rheumatic etiology prevailed, particularly in southern regions (48.8%). Multivalvular involvement was observed in 47.4% of RVD cases, and atrial fibrillation emerged as the most common comorbidity (43.2%). Severe RVD affected 64.2% of patients. Valvular interventions were undertaken by 66.9% of RVD patients, predominantly involving surgical valve replacement (90.8%). Adverse events, encompassing all-cause mortality and heart failure hospitalization, occurred in 7.3% of patients during the 2-year follow-up. Multivariable analysis identified factors such as age, geographical region, low body mass index, renal insufficiency, left atrial diameter, and left ventricular ejection fraction <50% (all P < 0.05) associated with adverse events, with valvular intervention emerging as a protective factor (HR: 0.201; 95%CI: 0.139 to 0.291; p < 0.001). Conclusions: This study delivers a comprehensive evaluation of RVD patients in China, shedding light on the spectrum, characteristics, investigation, management, and outcomes of this prevalent condition.

Prevalence and impact of diabetes in patients with valvular heart disease.

This study aimed to investigate the prevalence of diabetes in valvular heart disease (VHD), as well as the relationship of diabetes with severity of valvular lesions and clinical outcome. A total of 11,862 patients with significant (≥moderate) VHD from the China Valvular Heart Disease study were included in the analysis. The primary outcome was the composite of all-cause death, hospitalization for heart failure, and myocardial infarction during two-year follow-up. The prevalence of diabetes was 14.5% (1,721/11,862) in VHD. After adjusting for patients' demographics, diabetes was associated with a significantly lower risk of severe valvular lesion in aortic regurgitation and mitral regurgitation (MR). In multivariable analysis, diabetes was identified as an independent predictor of two-year outcome in patients with MR (hazard ratio: 1.345, 95% confidence interval: 1.069-1.692, p = 0.011). More efforts should be made to enhance our understanding and improve outcomes of concomitant VHD and diabetes.

Meta-Analysis Global Group in Chronic Heart Failure score for the prediction of mortality in valvular heart disease.

AIMS: Valvular heart disease (VHD) is one of the leading causes of heart failure. Clinically significant VHD can induce different patterns of cardiac remodelling, and risk stratification is challenging in patients with various degrees of cardiac dysfunction. The study aimed to investigate the prognostic implications of Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score in patients with VHD. METHODS AND RESULTS: This study used data from the China Valvular Heart Disease (China-VHD) registry, which was a multicentre, prospective, observational cohort study for patients with significant (at least moderate) VHD. In total, 10 446 patients with moderate or greater VHD from the China-VHD study were included in the present analysis. The primary outcome of interest was all-cause mortality within 2 years. Among 10 446 patients with VHD, the mean age was 61.98 ± 13.47 years, and 5819 (55.7%) were male. During 2 years of follow-up, 895 (8.6%) patients died. The MAGGIC score was monotonically and independently associated with mortality in both total cohort [adjusted hazard ratio: 1.095, 95% confidence interval (CI): 1.084-1.107, P < 0.001] and most types of VHD (aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid regurgitation, mixed aortic stenosis and aortic regurgitation, and multiple VHD). The score was also an independent prognostic factor in patients with or without symptoms or preserved left ventricular ejection fraction (LVEF) and exhibited both satisfactory discrimination and calibration properties in predicting mortality. The prognostic value of MAGGIC score was robust in most quartiles of N-terminal pro-brain natriuretic peptide level, with no significant interaction observed (Pinteraction  = 0.498). Compared with the EuroSCORE II, the MAGGIC score achieved significantly better predictive performance in overall population [C index: 0.769 vs. 0.727; net reclassification improvement index (95% CI): 0.354 (0.313-0.396), P < 0.001; integrated discrimination improvement index (95% CI): 0.069 (0.052-0.085), P < 0.001] and in subgroups of patients divided by therapeutic strategy, LVEF, symptomatic status, stage of VHD, and aetiology of VHD. CONCLUSIONS: The MAGGIC score is a reliable prognostic factor across the range of cardiac dysfunction in VHD and may assist in risk stratification and guide clinical decision-making.

Development and validation of a score predicting mortality for older patients with mitral regurgitation.

OBJECTIVE: To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score. METHODS: The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion. RESULTS: Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m2, NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m2, albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01). CONCLUSIONS: The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

Total Cholesterol Levels and Risk of Mortality or Heart Failure Rehospitalization in Patients With Valvular Heart Disease.

Low total cholesterol (TC) levels have been found to significantly increase mortality risk in patients experiencing heart failure. However, it is unclear whether the same relation applies specifically to patients with valvular heart disease (VHD). This study included patients with significant VHD from the China Valvular Heart Disease Study. Patients with atherosclerotic cardiovascular disease were excluded. The primary end point of this study was a combined indicator of either all-cause mortality or rehospitalization because of heart failure (HF). The association between TC and the primary outcome was evaluated using Cox proportional hazard models. The cut-off value of TC for predicting mortality or rehospitalization was determined by the maximally selected rank test. The study population comprised 6,235 patients with VHD. Over a 2-year follow-up period, there were 393 deaths and 265 HF rehospitalizations. The adjusted hazard models showed that for every 1 mmol/L decrease in TC, there was a 1.19-fold increased risk of death or HF rehospitalization (adjusted hazard ratio 1.19, 95% confidence interval 1.09 to 1.30, p <0.001). The optimal cut-off value of TC was 3.53 mmol/L; patients at or below this level had significantly higher mortality and HF rehospitalization rates. After adjustment for confounding factors, low TC levels (≤3.53 mmol/L) remained a significant risk factor for patients with aortic regurgitation, mitral regurgitation, and tricuspid regurgitation. Decreased TC levels are associated with an increased risk of death or HF rehospitalization among patients with VHD.

Assessment of cardio-renal-hepatic function in patients with valvular heart disease: a multi-biomarker approach-the cardio-renal-hepatic score.

BACKGROUND: Valvular heart disease (VHD) can cause damage to extra-cardiac organs, and lead to multi-organ dysfunction. However, little is known about the cardio-renal-hepatic co-dysfunction, as well as its prognostic implications in patients with VHD. The study sought to develop a multi-biomarker index to assess heart, kidney, and liver function in an integrative fashion, and investigate the prognostic role of cardio-renal-hepatic function in VHD. METHODS: Using a large, contemporary, prospective cohort of 6004 patients with VHD, the study developed a multi-biomarker score for predicting all-cause mortality based on biomarkers reflecting heart, kidney, and liver function (N-terminal pro-B-type natriuretic peptide [NT-proBNP], creatinine, and albumin). The score was externally validated in another contemporary, prospective cohort of 3156 patients with VHD. RESULTS: During a median follow up of 731 (704-748) days, 594 (9.9%) deaths occurred. Increasing levels of NT-proBNP, creatinine, and albumin were independently and monotonically associated with mortality, and a weighted multi-biomarker index, named the cardio-renal-hepatic (CRH) score, was developed based on Cox regression coefficients of these biomarkers. The CRH score was a strong and independent predictor of mortality, with 1-point increase carrying over two times of mortality risk (overall adjusted hazard ratio [95% confidence interval]: 2.095 [1.891-2.320], P < 0.001). The score provided complementary prognostic information beyond conventional risk factors (C index: 0.78 vs 0.81; overall net reclassification improvement index [95% confidence interval]: 0.255 [0.204-0.299]; likelihood ratio test P < 0.001), and was identified as the most important predictor of mortality by the proportion of explainable log-likelihood ratio χ2 statistics, the best subset analysis, as well as the random survival forest analysis in most types of VHD. The predictive performance of the score was also demonstrated in patients under conservative treatment, with normal left ventricular systolic function, or with primary VHD. It achieved satisfactory discrimination (C index: 0.78 and 0.72) and calibration in both derivation and validation cohorts. CONCLUSIONS: A multi-biomarker index was developed to assess cardio-renal-hepatic function in patients with VHD. The cardio-renal-hepatic co-dysfunction is a powerful predictor of mortality and should be considered in clinical management decisions.

Development and validation of dynamic models to predict postdischarge mortality risk in patients with acute myocardial infarction: results from China Acute Myocardial Infarction Registry.

OBJECTIVES: The risk of adverse events and prognostic factors are changing in different time phases after acute myocardial infarction (AMI). The incidence of adverse events is considerable in the early period after AMI hospitalisation. Therefore, dynamic risk prediction is needed to guide postdischarge management of AMI. This study aimed to develop a dynamic risk prediction instrument for patients following AMI. DESIGN: A retrospective analysis of a prospective cohort. SETTING: 108 hospitals in China. PARTICIPANTS: A total of 23 887 patients after AMI in the China Acute Myocardial Infarction Registry were included in this analysis. PRIMARY OUTCOME MEASURES: All-cause mortality. RESULTS: In multivariable analyses, age, prior stroke, heart rate, Killip class, left ventricular ejection fraction (LVEF), in-hospital percutaneous coronary intervention (PCI), recurrent myocardial ischaemia, recurrent myocardial infarction, heart failure (HF) during hospitalisation, antiplatelet therapy and statins at discharge were independently associated with 30-day mortality. Variables related to mortality between 30 days and 2 years included age, prior renal dysfunction, history of HF, AMI classification, heart rate, Killip class, haemoglobin, LVEF, in-hospital PCI, HF during hospitalisation, HF worsening within 30 days after discharge, antiplatelet therapy, ß blocker and statin use within 30 days after discharge. The inclusion of adverse events and medications significantly improved the predictive performance of models without these indexes (likelihood ratio test p<0.0001). These two sets of predictors were used to establish dynamic prognostic nomograms for predicting mortality in patients with AMI. The C indexes of 30-day and 2-year prognostic nomograms were 0.85 (95% CI 0.83-0.88) and 0.83 (95% CI 0.81-0.84) in derivation cohort, and 0.79 (95% CI 0.71-0.86) and 0.81 (95% CI 0.79-0.84) in validation cohort, with satisfactory calibration. CONCLUSIONS: We established dynamic risk prediction models incorporating adverse event and medications. The nomograms may be useful instruments to help prospective risk assessment and management of AMI. TRIAL REGISTRATION NUMBER: NCT01874691.

Prognostic value of modified model for end-stage liver disease scores in patients with significant tricuspid regurgitation.

AIMS: Tricuspid regurgitation (TR) may cause damage to liver and kidney function. The Model for End-Stage Liver Disease excluding international normalized ratio (MELD-XI) and the model with albumin replacing international normalized ratio (MELD-Albumin) scores, which include both liver and kidney function indexes, may predict mortality in patients with TR. The study aimed to analyse the prognostic value of MELD-XI and MELD-Albumin scores in patients with significant TR. METHODS AND RESULTS: A total of 1825 patients with at least moderate pure native TR from the China Valvular Heart Disease study between April and June 2018, were included in this analysis. The primary outcome was all-cause death within 2 years. Of 1825 patients, 165 (9.0%) died during follow-up. Restricted cubic splines revealed that hazard ratio for death increased monotonically with greater modified MELD scores. The MELD-XI and MELD-Albumin scores, as continuous variables or categorized using thresholds determined by maximally selected rank statistics, were independently associated with 2-year mortality (all adjusted P < 0.001). Both scores provided incremental value over prognostic model without hepatorenal indexes {MELD-XI score: net reclassification index [95% confidence interval (95% CI), 0.237 (0.138-0.323)]; MELD-Albumin score: net reclassification index (95% CI), 0.220 (0.122-0.302)}. Results were similar in clinically meaningful subgroups, including but not limited to patients under medical treatment and those with normal left ventricular ejection fraction. Models including modified MELD scores were established for prognostic evaluation of significant TR. CONCLUSION: Both MELD-XI and MELD-Albumin scores provided incremental prognostic information and could play important roles in risk assessment in patients with significant TR.

Prognostic value of blood pressure and resting heart rate in patients with tricuspid regurgitation.

Background: The prognostic value of blood pressure (BP) and resting heart rate (RHR) in tricuspid regurgitation (TR) patients is unknown. Aims: This study aimed to investigate the associations of BP and RHR with all-cause mortality in patients with TR. Methods: A total of 2,013 patients with moderate or severe TR underwent echocardiography and BP measurement. The associations of routinely measured BP and RHR with 2-year all-cause mortality were analyzed. Results: The cohort had 45.9% male patients and a mean age of 62.5 ± 15.9 years. At the 2-year follow-up, 165 patient deaths had occurred. The risk of death decreased rapidly, negatively correlating with systolic blood pressure (SBP) up to 120 mmHg and diastolic blood pressure (DBP) up to 70 mmHg. For RHR, the risk increased in direct proportion, starting at 80 beats per min. After adjusting for age, sex, body mass index (BMI), diabetes, coronary heart disease, pulmonary hypertension, estimated glomerular filtration rate (eGFR), and NYHA class, SBP [hazard ratio (HR):0.89; 95% CI:0.823-0.957 per 10 mmHg increase; P =0.002], DBP (HR:0.8; 95% CI:0.714-0.908 per 10 mmHg increase; P < 0.001), and RHR (HR: 1.1; 95% CI: 1.022-1.175 per 10 beats per min increase; P = 0.011) were independently associated with all-cause mortality. These associations persisted after further adjustments for echocardiographic indices, medications, serological tests, and etiologies. Conclusion: In this cohort of patients with TR, routinely measured BP and RHR were associated with all-cause mortality independently. However, further large-scale, high-quality studies are required to validate our findings.

Length of Stay and Short-Term Outcomes in Patients with ST-Segment Elevation Myocardial Infarction After Primary Percutaneous Coronary Intervention: Insights from the China Acute Myocardial Infarction Registry.

BACKGROUND: Length of stay (LOS) in patients with ST-segment elevation myocardial infarction (STEMI) is directly associated with financial pressure and medical efficiency. This study aimed to determine impact of LOS on short-term outcomes and associated factors of LOS in patients with ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI). METHODS: A total of 3615 patients with STEMI after PPCI in the China Acute Myocardial Infarction registry were included in the analysis. Predictors of prolonged LOS were analyzed by multivariate logistic regression model with generalized estimating equation. The impact of LOS on 30-day clinical outcomes was assessed. RESULTS: The median LOS was 9 (7, 12) days. Patients with a longer LOS (>7 days) were older, more often in lower-level hospitals, had more periprocedural complications and hospitalization expense. Fourteen variables, such as weekend admission and lower-level hospitals, were identified as independent associated factors of prolonged LOS. There were no significant difference in 30-day major adverse cardiac and cerebrovascular events (MACCE), readmission, and functional status between patients with LOS≤7d and LOS>7d after multivariate adjustment and propensity score matching. However, patients who discharged over one week had better medication adherence (adjusted odds ratio: 0.817, 95% confidence interval: 0.687-0.971, P=0.022). Significant interaction was observed in medication use between gender and LOS (Pinteraction=0.038). CONCLUSION: Patients with STEMI undergoing PPCI experienced a relatively long LOS in China, which resulted in more medical expenses but no improvement on 30-day MACCE, readmission, and functional recovery. Poor 30-day medication adherence with short LOS reflects unsatisfying transition of management from hospital to community. More efforts are needed to reduce LOS safely and improve the efficiency of medical care.

Clinical Characteristics, Prognosis, and Gender Disparities in Young Patients With Acute Myocardial Infarction.

Background: Young people hold a stable or increasing percentage of patients with acute myocardial infarction (AMI) in many countries. However, data on clinical characteristics and outcomes of young AMI patients were insufficient. This study aimed to analyze clinical characteristics, prognosis, and gender disparities in patients aged ≤45 years with AMI. Methods: A total of 24,125 patients from China Acute Myocardial Infarction registry were included in this study. Clinical characteristics, managements, and in-hospital and 2-year outcomes were compared between patients aged ≤45 years and those aged >45 years. Predictors of all-cause death were obtained using multivariate regression models. Gender disparities of AMI were analyzed among young patients. Results: Of 24,125 patients, 2,042 (8.5%, 116 female) were aged ≤45 years. Compared with patients aged >45 years, young patients were more often male, current smokers, and more likely to have medical history of hyperlipidemia. Smoking (72.1%) was the major modifiable risk factor in patients aged ≤45 years. Young patients received more evidence-based medications and had significantly lower risk of both in-hospital and 2-year adverse events than older patients. Education level and left ventricular ejection fraction were independent predictors of 2-year mortality in young patients. Moreover, symptom onset to admission time of young women was significantly longer than that of young men. Young women were less likely to receive percutaneous coronary intervention and suffered higher risk of in-hospital adverse events than young men (adjusted odds ratio for death: 5.767, 95% confidence interval 1.580-21.049, p = 0.0080; adjusted odds ratio for the composite of death, re-infarction, and stroke: 3.981, 95% confidence interval 1.150-13.784, p = 0.0292). Young women who survived at discharge had a higher 2-year cumulative incidence of death (3.8 vs 1.4%, p log-rank = 0.0412). Conclusions: Patients aged ≤45 years constituted a non-negligible proportion of AMI patients, with higher prevalence of smoking and hyperlipidemia but better care and prognosis compared with older patients. There were significant gender disparities of managements and outcomes in young patients. More efforts to improve quality of care in young women are needed.

Prognostic Impact of Left Ventricular Ejection Fraction in Patients With Moderate Aortic Regurgitation: Potential Implications for Treatment Decision-Making.

BACKGROUND: The prognostic impact and optimal treatment of left ventricular systolic dysfunction in patients with moderate aortic regurgitation (AR) remain unknown. We aimed to assess the prognostic value of left ventricular ejection fraction (LVEF) in patients with moderate AR and explore the potential benefits of aortic valve intervention (AVI). METHODS: In total, 1,211 consecutive patients with moderate AR (jet width, 25-64% of LV outflow tract; vena contracta, 0.3-0.6 cm; regurgitant volume, 30-59 mL/beat; regurgitant fraction, 30-49%; effective regurgitation orifice, 0.10-0.29 cm2) prospectively registered between April and June 2018 at 46 academic hospitals were included. The primary outcome was a composite of death or hospitalization for heart failure (HHF). The optimal LVEF threshold for predicting the primary outcome was determined through the penalized spline shape and maximally selected rank statistics. RESULTS: During the 2-year follow-up, 125 deaths or HHF occurred. In the penalized splines, the relative hazard of death or HHF monotonically increased with decreasing LVEF. In the multivariate analysis, LVEF ≤55% was identified as the best threshold for independently predicting death or HHF under medical treatment (adjusted hazard ratio [HR]: 2.18; 95% confidence interval [CI] 1.38-3.42; P = 0.001), with substantial incremental values (integrated discrimination improvement index = 0.018, P = 0.030; net reclassification improvement index = 0.225, P = 0.006; likelihood ratio test P < 0.001). Among patients with LVEF 35-55%, AVI within 6 months of diagnosis was associated with a reduced risk of death or HHF compared with medical treatment alone (adjusted HR: 0.15; 95% CI: 0.04-0.50; P = 0.002), whereas this benefit was markedly attenuated when LVEF was ≤35% (adjusted HR: 0.65; 95% CI: 0.21-1.97; P = 0.441, P-interaction = 0.010) or >55% (adjusted HR: 0.40; 95% CI: 0.14-1.15; P = 0.089, P-interaction = 0.723). CONCLUSIONS: LVEF is an independent and incremental prognostic factor in patients with moderate AR, with LVEF ≤55% being a robust marker of poor prognosis. Patients with LVEF 35-55% may benefit from early surgical correction of moderate AR. Further studies are warranted to validate our findings in a randomized setting. REGISTRATION: China Valvular Heart Disease Study (China-VHD study, NCT03484806); clinicaltrials.gov/ct2/show/NCT03484806.

ß3GnT8 Promotes Colorectal Cancer Cells Invasion via CD147/MMP2/Galectin3 Axis.

ß1,3-N-acetylglucosaminyltransferase (ß3GnT8) and ß3GnT2 are key enzymes that catalyzes the formation of polylactosamine glycan structures by transferring GlcNAc to tetra-antennary ß1-6-branched N-glycan and it also has an important effect on the progression of various types of human cancer. They have been reported to participate in tumor invasion and metastasis by regulating the expression of matrix metalloproteinases (MMPs), CD147, and polylactosamine. However, whether ß3GnT8 and ß3GnT2 play a role in colorectal cancer and, if so, the underlying mechanisms remain unclear. In our study, we detected the expression of ß3GnT8, CD147, MMP2, and galectin3 by immunohistochemistry on 90 paraffin-embedded slices. And ß3GnT8, CD147, MMP2, and galectin3 were over-expressed in colorectal cancer tissues. We found that overexpression of ß3GnT8 and ß3GnT2 promoted invasion of colorectal cancer cells, whereas knockdown of ß3GnT8 and ß3GnT2 inhibited the invasive activity. Mechanistically, ß3GnT8 and ß3GnT2 regulated the expression of HG-CD147 and the level of polylactosamines in colorectal cancer cells. Together, these results illustrate that the novel role and the molecular mechanism of ß3GnT8 and ß3GnT2 in promotion of colorectal cancer invasion. These results suggest that the potential use of ß3GnT8 as a tumor target for the therapy of colorectal cancer.