Strategies and Mechanisms of First-Row Transition Metal-Regulated Radical C-H Functionalization.

Radical C-H functionalization represents a useful means of streamlining synthetic routes by avoiding substrate preactivation and allowing access to target molecules in fewer steps. The first-row transition metals (Ti, V, Cr, Mn, Fe, Co, Ni, and Cu) are Earth-abundant and can be employed to regulate radical C-H functionalization. The use of such metals is desirable because of the diverse interaction modes between first-row transition metal complexes and radical species including radical addition to the metal center, radical addition to the ligand of metal complexes, radical substitution of the metal complexes, single-electron transfer between radicals and metal complexes, hydrogen atom transfer between radicals and metal complexes, and noncovalent interaction between the radicals and metal complexes. Such interactions could improve the reactivity, diversity, and selectivity of radical transformations to allow for more challenging radical C-H functionalization reactions. This review examines the achievements in this promising area over the past decade, with a focus on the state-of-the-art while also discussing existing limitations and the enormous potential of high-value radical C-H functionalization regulated by these metals. The aim is to provide the reader with a detailed account of the strategies and mechanisms associated with such functionalization.

Prognostic effect of stress hyperglycemia ratio on patients with severe aortic stenosis receiving transcatheter aortic valve replacement: a prospective cohort study.

BACKGROUND: Stress hyperglycemia ratio (SHR) has recently been recognized as a novel biomarker that accurately reflects acute hyperglycemia status and is associated with poor prognosis of heart failure. We evaluated the relationship between SHR and clinical outcomes in patients with severe aortic stenosis receiving transcatheter aortic valve replacement (TAVR). METHODS: There were 582 patients with severe native aortic stenosis who underwent TAVR consecutively enrolled in the study. The formula used to determine SHR was as follows: admission blood glucose (mmol/L)/(1.59×HbA1c[%]-2.59). The primary endpoint was defined as all-cause mortality, while secondary endpoints included a composite of cardiovascular mortality or readmission for heart failure, and major adverse cardiovascular events (MACE) including cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke. Multivariable Cox regression and restricted cubic spline analysis were employed to assess the relationship between SHR and endpoints, with hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 3.9 years, a total of 130 cases (22.3%) of all-cause mortality were recorded. Results from the restricted cubic spline analysis indicated a linear association between SHR and all endpoints (p for non-linearity > 0.05), even after adjustment for other confounding factors. Per 0.1 unit increase in SHR was associated with a 12% (adjusted HR: 1.12, 95% CI: 1.04-1.21) higher incidence of the primary endpoint, a 12% (adjusted HR: 1.12, 95% CI: 1.02-1.22) higher incidence of cardiovascular mortality or readmission for heart failure, and a 12% (adjusted HR: 1.12, 95% CI: 1.01-1.23) higher incidence of MACE. Subgroup analysis revealed that SHR had a significant interaction with diabetes mellitus with regard to the risk of all-cause mortality (p for interaction: 0.042). Kaplan-Meier survival analysis showed that there were significant differences in the incidence of all endpoints between the two groups with 0.944 as the optimal binary cutoff point of SHR (all log-rank test: p < 0.05). CONCLUSIONS: Our study indicates linear relationships of SHR with the risk of all-cause mortality, cardiovascular mortality or readmission for heart failure, and MACE in patients with severe aortic stenosis receiving TAVR after a median follow-up of 3.9 years. Patients with an SHR exceeding 0.944 had a poorer prognosis compared to those with lower SHR values.

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.

A novel anatomic classification to guide transcatheter aortic valve replacement for pure aortic regurgitation.

BACKGROUND: The success of transcatheter aortic valve replacement (TAVR) in native aortic regurgitation (AR) is limited by the absence of calcified anchoring structures. We sought to evaluate transfemoral TAVR in patients with native AR using a novel aortic root imaging classification. METHODS: From March to November 2021, 81 patients with severe AR were prospectively enrolled in 2 cardiac centers in China. All were evaluated using multidetector computed tomography (MDCT) and classified into 4 anatomic types in reference to transcatheter heart valve (THV) anchoring: Type 1: anchoring at the left ventricular outflow tract (LVOT), annulus, and ascending aorta (AA); Type 2: anchoring at the annulus and AA; Type 3: anchoring at the annulus and LVOT; and Type 4: anchoring at only 1 level or none at all. Based on the dual-anchoring strategy, patients with Types 1-3 were considered TAVR candidates. Procedural and 30-day outcomes were assessed according to Valve Academic Research Consortium-3 definitions. RESULTS: TAVR was performed in 32 (39.5%) patients (71.9 ± 8.0 years of age, 71.9% were male) using 2 self-expanding THVs. Types 1, 2, and 3 comprised 13 (40.6%), 11 (34.4%), and 8 (25.0%) cases, respectively. The procedural and device success rates were 100% and 93.8%, respectively, with 2 THV migration. Eight patients (25.0%) required a permanent pacemaker, and 2 (6.3%) developed moderate paravalvular leaks. No deaths or other major complications occurred during the study. CONCLUSIONS: The novel anatomic classification and dual-anchoring strategy were associated with a high procedural success rate with favorable short-term safety and clinical outcomes.

CRNDE promotes cell tongue squamous cell carcinoma cell growth and invasion through suppressing miR-384.

Tongue squamous cell carcinoma (TSCC) is the most common type of oral cancer and is an aggressive head and neck malignancy. Increasing studies have demonstrated that long noncoding RNAs (lncRNAs) play important roles in diverse biological cell processes, such as cell development, fate decisions, cell differentiation, cell migration, and invasion. In our study, we showed that long noncoding RNA colorectal neoplasia differentially expressed (CRNDE) expression was upregulated in TSCC cell lines and tissues. Overexpression of CRNDE increased the TSCC cell proliferation, cell cycle, and cell invasion. Moreover, ectopic expression of CRNDE inhibited the miR-384 expression in the SCC1 cell and increased the Kirsten Ras (KRAS), cell division cycle 42, and insulin receptor substrate 1 expression, which were the direct target genes of miR-384. We demonstrated that the miR-384 expression was downregulated in the TSCC samples compared with the paired adjacent nontumor samples. The expression of CRNDE was negatively correlated with the expression of miR-384 in the TSCC samples. Overexpression of miR-384 suppressed TSCC cell proliferation, cell cycle, and invasion. Furthermore, we demonstrated that CRNDE promoted TSCC cell proliferation and invasion through inhibiting miR-384 expression. These results suggested that CRNDE acts as an oncogene in the development of TSCC, which partially occurs through inhibiting miR-384 expression.

The expression of Ubc9 and the intensity of SERCA2a-SUMOylation were reduced in diet-induced obese rats and partially restored by trimetazidine.

BACKGROUND: Reduced expression of sarcoplasmic reticulum calcium-transporting ATPase isoform 2a (SERCA2a) has been shown to play a significant role in the cardiac dysfunction of obese animal models. It was reported recently that SUMOylation enhances the stability and activity of SERCA2a. We hypothesized that SERCA2a-SUMOylation might be involved in obesity-mediated reduction of SERCA2a. METHOD AND RESULTS: Trimetazidine (TMZ), the drug that inhibits fatty acid oxidation, was used in diet-induced obese (DIO) rats and palmitic acid (PA)-treated cardiomyocytes. The intensity of SERCA2a-SUMOylation and proteins involved in SERCA2a-SUMOylation were investigated in vivo and in vitro. DIO rats presented cardiac dysfunction, which was alleviated by TMZ treatment. Reductions of SERCA2a protein and the intensity of SERCA2a-SUMOylation were observed in DIO rats and PA-treated cardiomyocytes. These reductions were partially restored by TMZ. However, TMZ itself did not alter the intensity of SERCA2a-SUMOylation in control cardiomyocytes. The variations of protein and messenger RNA levels of Ubiquitin carrier protein 9 are in accordance with the intensity of SERCA2a-SUMOylation. Whereas the other proteins involved in SERCA2a-SUMOylation were not changed by DIO and PA. CONCLUSIONS: TMZ alleviates the DIO- and PA-induced reductions of SERCA2a-SUMOylation. Ubiquitin carrier protein 9 is involved in the reductions.

The associations of "weekend warrior" and regularly active physical activity with abdominal and general adiposity in US adults.

OBJECTIVE: This study examined the association between physical activity patterns and abdominal and general adiposity. METHODS: Data were extracted among 20- to 59-year-old participants in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Abdominal and general adiposity was assessed by dual-energy x-ray absorptiometry (DXA) and anthropometric measures. DXA-measured indicators were further normalized into z scores. Physical activity levels were collected by questionnaire and classified as inactive, "weekend warrior" (WW), and regularly active (RA). Survey linear regression models were used to assess associations between physical activity patterns and adiposity indicators. RESULTS: Among 9629 participants, 772 (8.2%) reported the WW pattern and 3277 (36.9%) reported the RA pattern. Compared with inactive, both WW and RA had lower DXA-measured abdominal adiposity (WW: ß: -0.24, 95% CI: -0.38 to -0.10; RA: -0.18, 95% CI: -0.29 to -0.07), waist circumference (WW: ß: -1.94, 95% CI: -3.16 to -0.73; RA: -1.31, 95% CI: -2.32 to -0.29), whole-body fat mass (WW: ß: -0.16, 95% CI: -0.25 to -0.08; RA: -0.11, 95% CI: -0.18 to -0.04), and BMI (WW: ß: -0.78, 95% CI: -1.27 to -0.28; RA: -0.47, 95% CI: -0.89 to -0.04). CONCLUSIONS: The WW pattern was associated with similarly lower abdominal and general adiposity to the RA pattern versus the inactive pattern.

Prediction of hypoattenuating leaflet thickening in patients undergoing transcatheter aortic valves replacement based on clinical factors and 4D-computed tomography morphological characteristics: A retrospective cross-sectional study.

BACKGROUND: The rapid increase in the number of transcatheter aortic valve replacement (TAVR) procedures in China and worldwide has led to growing attention to hypoattenuating leaflet thickening (HALT) detected during follow-up by 4D-CT. It's reported that HALT may impact the durability of prosthetic valve. Early identification of these patients and timely deployment of anticoagulant therapy are therefore particularly important. METHODS: We retrospectively recruited 234 consecutive patients who underwent TAVR procedure in Fuwai Hospital. We collected clinical information and extracted morphological characteristics parameters of the transcatheter heart valve (THV) post TAVR procedure from 4D-CT. LASSO analysis was conducted to select important features. Three models were constructed, encapsulating clinical factors (Model 1), morphological characteristics parameters (Model 2), and all together (Model 3), to identify patients with HALT. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were plotted to evaluate the discriminatory ability of models. A nomogram for HALT was developed and verified by bootstrap resampling. RESULTS: In our study patients, Model 3 (AUC = 0.738) showed higher recognition effectiveness compared to Model 1 (AUC = 0.674, p = 0.032) and Model 2 (AUC = 0.675, p = 0.021). Internal bootstrap validation also showed that Model 3 had a statistical power similar to that of the initial stepwise model (AUC = 0.723 95%CI: 0.661-0.786). Overall, Model 3 was rated best for the identification of HALT in TAVR patients. CONCLUSION: A comprehensive predictive model combining patient clinical factors with CT-based morphology parameters has superior efficacy in predicting the occurrence of HALT in TAVR patients.

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.

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.

Association of psychological stress with wives' hypertension across over 10 million Chinese married female population aged 20-49 years.

BACKGROUND: Psychological stress has been reported to be a potential risk factor for hypertension among females, but it remains unclear whether spousal chronic stress levels alter the risk of hypertension among women. We examined the associations between stress within the family and hypertension among married women. METHODS: Reproductive-aged women who were planning for pregnancy and their husbands were recruited from the National Free Pre-pregnancy Checkup Projects (NFPCP) across 31 provinces in China in 2016 and 2017. Perceived stress of wives or husbands was measured with a 5-point Likert-type scale, and assessed from three domains: work/life-related stress, economic stress, and overall stress. Multivariable-adjusted logistic regression models were used to assess the associations between stress status and the prevalence of hypertension. RESULTS: Of 10,027,644 couples, 261,098 (2.60%) women had hypertension. The results showed that higher stress levels among themselves or their husbands were associated with a higher prevalence of hypertension in women ( Pfor trend <0.001). Compared with non-stressed participants, female participants with the highest stress themselves were at a greater risk of hypertension, with adjusted odds ratio (OR) of 1.31 (95% confidence interval [CI]: 1.25-1.37); and compared with participants whose husbands had no stress, those whose husbands had the highest stress level were at a higher risk of hypertension with adjusted OR of 1.24 (95% CI: 1.20-1.29). Moreover, compared with non-stressed status for both couples, only-wife-stressed, only-husband-stressed, and both-stressed couples were found to be significantly associated with increased risks of wives' hypertension, with adjusted ORs of 1.28 (95% CI: 1.25-1.31), 1.19 (95% CI: 1.17-1.21), and 1.28 (95% CI: 1.26-1.31), respectively. CONCLUSION: Moderate to severe stress in both spouses might be associated with female hypertension prevalence, which highlights the importance of paying attention to the psychological stresses of couples within the family.

Outcomes for patients undergoing transcatheter aortic valve replacement with ascending aorta dilation.

BACKGROUND: We aim to compare the short and long-term outcomes for aortic stenosis (AS) patients undergone TAVR with and without ascending aorta dilation (AAD). METHODS: Consecutive patients diagnosed with native severe AS who underwent TAVR from September 2012 to September 2021 were enrolled. They were stratified into the moderate/severe dilation group (greatest ascending aorta width ≥ 45 mm) and the non/mild dilation group. Survival outcomes were illustrated using Kaplan-Meier curves and evaluated with the log-rank test. Data from patients with CT follow-up of >6 months was used to investigate the progression rate of AAD. RESULTS: The study cohort comprised 556 patients, with a mean age of 75.5 ± 7.3 years. Among them, 107 patients (19.2%) had a moderate/severe AAD (≥45 mm), with an average diameter of 48.6 mm (±2.8). During hospitalization, both groups witnessed two cases of ascending aortic dissection (1.9% vs 0.4%, P = 0.380). The median follow-up duration was 3.9 years (95% CI: 3.8-4.0 years). No deaths were caused by aortic events and no patients experienced a new aortic dissection. The AAD cohort's 4-year all-cause and cardiovascular mortality rates were not significantly different to the non/mild dilation group's (log-rank test, P = 0.109 and P = 0.698, respectively). Follow-up CT data revealed that the rate of aortic dilation progression in the moderate/severe dilation group was not significantly different from that in the non/mild group (0.0 mm/year, 25-75%th: -0.3-0.2 vs 0.1 mm/year, 25-75%th: -0.3-0.4, P = 0.122). CONCLUSION: This study found no significant difference regarding short-term and long-term outcomes in AS patients with/without moderate/severe AAD undergoing TAVR.

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.

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.

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.

Can Measuring the 'Dual Anchors of Aorta' Enhance the Success Rate of TAVR?-A Single-Center Experience.

INTRODUCTION: Chronic severe aortic regurgitation (AR) has a poor long-term prognosis, especially among old-age patients. Considering their advancing age, the surgical approach of aortic valve replacement may not always be the best alternative modality of treatment in such patients. Therefore, this study's primary goal was to provide an initial summary of the medium- and short-term clinical effectiveness of transcatheter aortic valve replacement (TAVR) guided by accurate multi-detector computed tomography (MDCT) measurements in patients with severe and chronic AR, especially in elderly patients. METHODS: The study enrolled retrospectively and prospectively patients diagnosed with severe AR who eventually underwent TAVR procedure from January 2019 to September 2022 at Fuwai cardiovascular Hospital, Beijing. Baseline information, MDCT measurements, anatomical classification, perioperative, and 1-year follow-up outcomes were collected and analyzed. Based on a novel anatomical categorization and dual anchoring theory, patients were divided into four categories according to the level of anchoring area. Type 1, 2, and 3 patients (with at least two anchoring regions) will receive TAVR with a transcatheter heart valve (THV), but Type 4 patients (with zero or one anchoring location) will be deemed unsuitable for TAVR and will instead receive medical care (retrospectively enrolled patients who already underwent TAVR are an exception). RESULTS: The mean age of the 37 patients with severe chronic AR was 73.1 ± 8.7 years, and 23 patients (62.2%) were male. The American Association of Thoracic Surgeons' score was 8.6 ± 2.1%. The MDCT anatomical classification included 17 cases of type 1 (45.9%), 3 cases of type 2 (8.1%), 13 cases of type 3 (35.1%), and 4 cases of Type 4 (10.8%). The VitaFlow valve (MicroPort, Shanghai, China) was implanted in 19 patients (51.3%), while the Venus A valve (Venus MedTech, Hangzhou, China) was implanted in 18 patients (48.6%). Immediate TAVR procedural and device success rates were 86.5% and 67.6%, respectively, while eight cases (21.6%) required THV-in-THV implantation, and nine cases (24.3%) required permanent pacemaker implantation. Univariate regression analysis revealed that the major factors affecting TAVR device failure were sinotubular junction diameter, THV type, and MDCT anatomical classification (p < 0.05). Compared with the baseline, the left ventricular ejection fraction gradually increased, while the left ventricular end-diastolic diameter remained small, and the N-terminal-pro hormone B-type natriuretic peptide level significantly decreased within one year. CONCLUSION: According to the results of our study, TAVR with a self-expanding THV is safe and feasible for patients with chronic severe AR, particularly for those who meet the criteria for the appropriate MDCT anatomical classification with intact dual aortic anchors, and it has a significant clinical effect for at least a year.

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.

Prognostic Value of Baseline d-Dimer Level in Patients With Coronary Artery Disease: A Meta-Analysis.

The prognostic significance of d-dimer level in patients with coronary artery disease (CAD) is not fully established. This meta-analysis aimed to examine the association between elevated d-dimer level at baseline and adverse outcomes in patients with CAD. Two independent authors comprehensively searched PubMed and Embase databases from their inception to December 31, 2020. All observational studies reporting the values of baseline d-dimer level in predicting the major adverse cardiovascular events (MACEs) or survival outcomes in patients with CAD were included. The prognostic values were calculated by pooling adjusted RR with 95% CI for the highest versus the lowest d-dimer level. Thirteen studies consisting of 25 600 patients with CAD were identified. Comparison between the highest and lowest d-dimer level showed that the pooled multivariable adjusted RR was 1.69 (95% CI, 1.53-1.86) for all-cause mortality, 2.37 (95% CI, 1.52-3.69) for cardiovascular mortality, and 1.44 (95% CI, 1.19-1.74) for MACEs, respectively. Elevated blood level of d-dimer at baseline was independently associated with higher risk of MACEs, cardiovascular death, and all-cause mortality in patients with CAD. The baseline d-dimer level may have important prognostic value in patients with CAD.

Prior percutaneous coronary intervention and outcomes in patients after coronary artery bypass grafting: a meta-analysis of 308,284 patients.

Background: The association between prior percutaneous coronary intervention (PCI) and prognosis after coronary artery bypass grafting (CABG) remains uncertain. We aimed to evaluate the aforementioned association in a meta-analysis. Methods: PubMed, Cochrane's Library, and Embase databases were searched for potential studies. A random-effects model was used for the meta-analysis. Meta-regression was performed to evaluate the influence of study characteristics on the outcomes. Results: Thirty-six follow-up studies with 308,284 patients were included, and 40,892 (13.3%) patients had prior PCI. Pooled results showed that prior PCI was associated with higher risks of early (in-hospital or within 1 month) all-cause mortality [odds ratio (OR): 1.26, 95% confidence interval (CI): 1.11-1.44, p = 0.003; I 2 = 64%] and major adverse cardiovascular events (MACEs; OR: 1.36, 95% CI: 1.12-1.66, p = 0.002, I 2 = 79%), but not with late (follow-up durations from 1 to 13 years) mortality (OR: 1.03, 95% CI: 0.95-1.13, p = 0.44, I 2 = 46%) or MACEs (OR: 1.03, 95% CI: 0.97-1.09, p = 0.38, I 2 = 0%). Meta-regression showed that the study characteristics of patient number, age, sex, diabetic status, and proportion of patients with prior PCI did not affect the outcomes. Sensitivity analyses limited to multivariate studies excluding patients with acute PCI failure showed similar results (early mortality, OR: 1.25, p = 0.003; early MACE, OR: 1.50, p = 0.001; late mortality, OR: 1.03, p = 0.70). Conclusion: The current evidence, mostly from retrospective observational studies, suggests that prior PCI is related to poor early clinical outcomes, but not to late clinical outcomes, after CABG.

The effects of levosimendan in patients undergoing transcatheter aortic valve replacement- a retrospective analysis.

Background: Aortic stenosis (AS) increases left ventricular afterload, leading to cardiac damage and heart failure (HF). Transcatheter aortic valve replacement (TAVR) is an effective therapy for AS. No inotropic agents including levosimendan have been evaluated in patients undergoing TAVR. Methods: A total of 285 patients underwent TAVR between 2014 and 2019; 210 were included in the matched analysis and 105 received 0.1 µg/kg body weight/min levosimendan immediately after the prosthesis had been successfully implanted. Medical history, laboratory tests, and echocardiography results were analyzed. Endpoints including 2-year all-cause mortality, stroke, or HF-related hospitalization, and a combination of the above were analyzed by Cox proportional hazard models. Results: The levosimendan group had no difference in 2-year mortality compared with the control group (hazard ratio [HR]: 0.603, 95% confidence interval [CI]: 0.197-1.844; p = 0.375). However, levosimendan reduced stroke or HF-related hospitalization (HR: 0.346; 95% CI: 0.135-0.884; p = 0.027) and the combined endpoint (HR: 0.459, 95% CI: 0.215-0.980; p = 0.044). After adjusting for multiple variants, levosimendan still reduced stroke or HF-related hospitalization (HR: 0.346, 95% CI: 0.134-0.944; p = 0.038). Conclusion: Prophylactic levosimendan administration immediately after valve implantation in patients undergoing TAVR can reduce stroke or HF-related hospitalization but does not lower all-cause mortality.