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.

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.

A Novel System for Transcatheter Aortic Valve Implantation: First-in-Man Study.

Transcatheter aortic valve implantation (TAVI) has become a therapeutic treatment for severe symptomatic patients with aortic stenosis. This study aimed to test a novel transcatheter aortic self-expandable bioprosthesis-the ScienCrown system (Lepu Medtech Inc., Beijing, China)-and evaluate the safety of the new device during TAVI. ScienCrown aortic valve implantation was performed on 10 patients. Clinical assessment was performed at baseline, post procedure, and after 1 year. Clinical outcomes and adverse events were assessed according to Valvular Academic Research Consortium-3 criteria. The mean age was 75.30 ± 4.78 years with a mean Society of Thoracic Surgeons score of 4.64 ± 3.23%. Device success was achieved in all patients (80% transfemoral, 20% transapical). After 1 year, there were no deaths, disabling strokes, myocardial infarctions, conversions to surgery, or major procedure-related complications. New pacemaker implantation was required in one patient (10%). ScienCrown implantation resulted in a reduction in mean valve gradient (63.00 ± 18.84 to 9.67 ± 4.97 mm Hg, p <0.001) and an increase in effective orifice area (0.57 ± 0.20 to 2.57 ± 0.59 cm2, p <0.001) at 1 year. Paravalvular leak was absent in 9 patients (90%), and there was a trace in one patient (10%). All patients were in New York Heart Association class I to II at a mean follow-up of 1 year. The experience showed that ScienCrown transcatheter aortic valve system was safely and successfully implanted for treatment of severe symptomatic aortic stenosis. The newer-generation device affords a stable implantation while providing optimal hemodynamic performance.

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.

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 study of the novel SinoCrown system for transcatheter aortic valve implantation.

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.

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.

Genetic association of lipids and lipid-lowering drug target genes with non-alcoholic fatty liver disease.

BACKGROUND:Some observational studies found that dyslipidaemia is a risk factor for non-alcoholic fatty liver disease (NAFLD), and lipid-lowering drugs may lower NAFLD risk. However, it remains unclear whether dyslipidaemia is causative for NAFLD. This Mendelian randomisation (MR) study aimed to explore the causal role of lipid traits in NAFLD and evaluate the potential effect of lipid-lowering drug targets on NAFLD.METHODS:Genetic variants associated with lipid traits and variants of genes encoding lipid-lowering drug targets were extracted from the Global Lipids Genetics Consortium genome-wide association study (GWAS). Summary statistics for NAFLD were obtained from two independent GWAS datasets. Lipid-lowering drug targets that reached significance were further tested using expression quantitative trait loci data in relevant tissues. Colocalisation and mediation analyses were performed to validate the robustness of the results and explore potential mediators.FINDINGS:No significant effect of lipid traits and eight lipid-lowering drug targets on NAFLD risk was found. Genetic mimicry of lipoprotein lipase (LPL) enhancement was associated with lower NAFLD risks in two independent datasets (OR1 = 0.60 [95% CI 0.50-0.72], p1 = 2.07 × 10-8; OR2 = 0.57 [95% CI 0.39-0.82], p2 = 3.00 × 10-3). A significant MR association (OR = 0.71 [95% CI, 0.58-0.87], p = 1.20 × 10-3) and strong colocalisation association (PP.H4 = 0.85) with NAFLD were observed for LPL expression in subcutaneous adipose tissue. Fasting insulin and type 2 diabetes mediated 7.40% and 9.15%, respectively, of the total effect of LPL on NAFLD risk.INTERPRETATION:Our findings do not support dyslipidaemia as a causal factor for NAFLD. Among nine lipid-lowering drug targets, LPL is a promising candidate drug target in NAFLD. The mechanism of action of LPL in NAFLD may be independent of its lipid-lowering effects.FUNDING:Capital's Funds for Health Improvement and Research (2022-4-4037). CAMS Innovation Fund for Medical Sciences (CIFMS, grant number: 2021-I2M-C&T-A-010).

Computed tomography anatomical characteristics based on transcatheter aortic valve replacement in aortic regurgitation.

This study analyzed computed tomography (CT) measurement characteristics and anatomical classifications based on transcatheter aortic valve replacement (TAVR) in patients with aortic regurgitation (AR) to establish a preliminary summary of CT anatomical characteristics and to design a novel self-expanding transcatheter heart valve (THV). This single-center retrospective cohort study included 136 patients diagnosed with moderate-to-severe AR at Fuwai Hospital from July 2017 to April 2022. Patients were classified into four anatomical classifications according to dual-anchoring multiplanar measurement of where THV anchoring took place. Types 1-3 were considered candidates for TAVR, whereas type 4 was not. Among 136 patients with AR, there were 117 (86.0%) tricuspid, 14 bicuspid, and five quadricuspid valves. Dual-anchoring multiplanar measurement showed that the annulus was smaller than left ventricular outflow tract (LVOT) at 2, 4, 6, 8, and 10 mm on the annulus. The ascending aorta (AA) 40 mm was wider than AA 30 mm and AA 35 mm, but narrower than AA 45 mm and AA 50 mm. For 10% oversize of the THV, the proportions of the annulus, LVOT, and AA unable to meet the diameter were 22.8%, 37.5%, and 50.0%, respectively, and the proportions of anatomical classification types 1-4 were 32.4%, 5.9%, 30.1%, and 31.6%, respectively. The novel THV could significantly improve the type 1 proportion (88.2%). Existing THVs cannot meet the anatomical characteristics of patients with AR. Conversely, based on anatomical characteristics, the novel THV could theoretically facilitate TAVR.

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.

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.

A Novel System for Transcatheter Aortic Valve Implantation: First-in-Man Study.

Transcatheter aortic valve implantation (TAVI) has become a therapeutic treatment for severe symptomatic patients with aortic stenosis. This study aimed to test a novel transcatheter aortic self-expandable bioprosthesis-the ScienCrown system (Lepu Medtech Inc., Beijing, China)-and evaluate the safety of the new device during TAVI. ScienCrown aortic valve implantation was performed on 10 patients. Clinical assessment was performed at baseline, post procedure, and after 1 year. Clinical outcomes and adverse events were assessed according to Valvular Academic Research Consortium-3 criteria. The mean age was 75.30 ± 4.78 years with a mean Society of Thoracic Surgeons score of 4.64 ± 3.23%. Device success was achieved in all patients (80% transfemoral, 20% transapical). After 1 year, there were no deaths, disabling strokes, myocardial infarctions, conversions to surgery, or major procedure-related complications. New pacemaker implantation was required in one patient (10%). ScienCrown implantation resulted in a reduction in mean valve gradient (63.00 ± 18.84 to 9.67 ± 4.97 mm Hg, p <0.001) and an increase in effective orifice area (0.57 ± 0.20 to 2.57 ± 0.59 cm2, p <0.001) at 1 year. Paravalvular leak was absent in 9 patients (90%), and there was a trace in one patient (10%). All patients were in New York Heart Association class I to II at a mean follow-up of 1 year. The experience showed that ScienCrown transcatheter aortic valve system was safely and successfully implanted for treatment of severe symptomatic aortic stenosis. The newer-generation device affords a stable implantation while providing optimal hemodynamic performance.

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.

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 study of the novel SinoCrown system for transcatheter aortic valve implantation.

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.

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.

Genetic association of lipids and lipid-lowering drug target genes with non-alcoholic fatty liver disease.

BACKGROUND:Some observational studies found that dyslipidaemia is a risk factor for non-alcoholic fatty liver disease (NAFLD), and lipid-lowering drugs may lower NAFLD risk. However, it remains unclear whether dyslipidaemia is causative for NAFLD. This Mendelian randomisation (MR) study aimed to explore the causal role of lipid traits in NAFLD and evaluate the potential effect of lipid-lowering drug targets on NAFLD.METHODS:Genetic variants associated with lipid traits and variants of genes encoding lipid-lowering drug targets were extracted from the Global Lipids Genetics Consortium genome-wide association study (GWAS). Summary statistics for NAFLD were obtained from two independent GWAS datasets. Lipid-lowering drug targets that reached significance were further tested using expression quantitative trait loci data in relevant tissues. Colocalisation and mediation analyses were performed to validate the robustness of the results and explore potential mediators.FINDINGS:No significant effect of lipid traits and eight lipid-lowering drug targets on NAFLD risk was found. Genetic mimicry of lipoprotein lipase (LPL) enhancement was associated with lower NAFLD risks in two independent datasets (OR1 = 0.60 [95% CI 0.50-0.72], p1 = 2.07 × 10-8; OR2 = 0.57 [95% CI 0.39-0.82], p2 = 3.00 × 10-3). A significant MR association (OR = 0.71 [95% CI, 0.58-0.87], p = 1.20 × 10-3) and strong colocalisation association (PP.H4 = 0.85) with NAFLD were observed for LPL expression in subcutaneous adipose tissue. Fasting insulin and type 2 diabetes mediated 7.40% and 9.15%, respectively, of the total effect of LPL on NAFLD risk.INTERPRETATION:Our findings do not support dyslipidaemia as a causal factor for NAFLD. Among nine lipid-lowering drug targets, LPL is a promising candidate drug target in NAFLD. The mechanism of action of LPL in NAFLD may be independent of its lipid-lowering effects.FUNDING:Capital's Funds for Health Improvement and Research (2022-4-4037). CAMS Innovation Fund for Medical Sciences (CIFMS, grant number: 2021-I2M-C&T-A-010).

Computed tomography anatomical characteristics based on transcatheter aortic valve replacement in aortic regurgitation.

This study analyzed computed tomography (CT) measurement characteristics and anatomical classifications based on transcatheter aortic valve replacement (TAVR) in patients with aortic regurgitation (AR) to establish a preliminary summary of CT anatomical characteristics and to design a novel self-expanding transcatheter heart valve (THV). This single-center retrospective cohort study included 136 patients diagnosed with moderate-to-severe AR at Fuwai Hospital from July 2017 to April 2022. Patients were classified into four anatomical classifications according to dual-anchoring multiplanar measurement of where THV anchoring took place. Types 1-3 were considered candidates for TAVR, whereas type 4 was not. Among 136 patients with AR, there were 117 (86.0%) tricuspid, 14 bicuspid, and five quadricuspid valves. Dual-anchoring multiplanar measurement showed that the annulus was smaller than left ventricular outflow tract (LVOT) at 2, 4, 6, 8, and 10 mm on the annulus. The ascending aorta (AA) 40 mm was wider than AA 30 mm and AA 35 mm, but narrower than AA 45 mm and AA 50 mm. For 10% oversize of the THV, the proportions of the annulus, LVOT, and AA unable to meet the diameter were 22.8%, 37.5%, and 50.0%, respectively, and the proportions of anatomical classification types 1-4 were 32.4%, 5.9%, 30.1%, and 31.6%, respectively. The novel THV could significantly improve the type 1 proportion (88.2%). Existing THVs cannot meet the anatomical characteristics of patients with AR. Conversely, based on anatomical characteristics, the novel THV could theoretically facilitate TAVR.