Stress hyperglycemia ratio as a prognostic indicator for long-term adverse outcomes in heart failure with preserved ejection fraction.

BACKGROUND: Recent studies highlighted that stress hyperglycemia ratio (SHR) is a potential predictor for future risk in heart failure (HF) patients. However, its implications specifically in HF with preserved ejection fraction (HFpEF) are not yet fully elucidated. We aimed to investigate the association between SHR and long-term clinical outcomes in HFpEF patients. METHODS: HFpEF patients enrolled between 2015 and 2023, were followed (mean 41 months) for a composite outcome of all-cause, cardiovascular mortality, and HF rehospitalization. SHR was established as the ratio of acute-chronic glycemia from admission blood glucose and glycated hemoglobin. The optimal cut-off for SHR to predict outcomes based on event prediction was determined through ROC analysis, and the cutoff was identified at 0.99. The effect of SHR on adverse risk was examined through the Cox hazards and Kaplan-Meier survival methods. A Pearson correlation analysis was conducted to assess the relationship between SHR and the severity of HF, as indicated by N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Furthermore, the incremental prognostic value of SHR was further assessed by the integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). RESULTS: Among the 400 enrolled patients, 190 individuals (47.5%) encountered composite events over the 41-month follow-up period. SHR was significantly elevated in patients with events compared with those without (p < 0.001). All patients were stratified into high SHR (n = 124) and low SHR (n = 276) groups based on the SHR cutoff. The high SHR group had a significantly higher incidence of adverse events than the low SHR group (log-rank; p < 0.001). Additional analysis indicated a poorer prognosis in patients with low left ventricular EF (LVEF) levels (50 < LVEF < 60) and high SHR (SHR > 0.99) in comparison to the other groups (log-rank p < 0.001). In adjusted analysis, after accounting for age, sex, diabetes, and NT-proBNP, elevated SHR remained independently predictive of adverse outcomes (adjusted HR: 2.34, 95% CI 1.49-3.67; p < 0.001). Furthermore, adding SHR to a model with MAGGIC score provided an incremental improvement in predicting adverse events. Additionally, SHR displayed a slight correlation with NT-proBNP. CONCLUSION: Elevated SHR was independently associated with an increased risk for composite events of all-cause, cardiovascular mortality, and HF readmission than those with lower SHR. SHR is a valuable tool for predicting and stratifying long-term adverse risks among HFpEF patients.

Prognostic impact of coronary microvascular dysfunction in patients with atrial fibrillation.

BACKGROUND: Coronary microvascular dysfunction (CMD) is frequently observed in atrial fibrillation (AF), the most commonly sustained arrhythmia. Nevertheless, an in-depth prognostic significance of CMD in AF is lacking. We aimed to provide insight into the predictive impact of CMD assessed by a novel non-invasive coronary angiography-derived index of microcirculatory resistance (caIMR) for major adverse events (MACE) in AF patients. METHOD: This study included patients with AF who underwent invasive coronary angiography due to suspected cardiac ischemia and did not exhibit obstructive epicardial coronary artery disease (≤50 % stenosis). The caIMR was prospectively evaluated, and the optimal cutoff value for predicting MACE was determined through ROC analysis. RESULT: A total of 463 patients with AF were enrolled. During a median of 33 months of follow-up, 111 (23.97 %) patients had MACE endpoints. The best caIMR cutoff value was 39.28. In patients with MACE, both the mean caIMR and the prevalence of elevated caIMR (caIMR>39.28) were significantly higher compared to those without MACE. An elevated caIMR was linked to a higher risk of MACE (log-rank P < 0.001) and emerged as an independent predictor of clinical outcomes (HR: 4.029; 95 % CI: 2.529-6.418; P < 0.001). In addition, the risk of MACE was higher in high caIMR patients with non-paroxysmal AF (log-rank P < 0.001) and no catheter ablation (log-rank P < 0.001). CONCLUSION: Elevated caIMR is common and showed a vital independent prognostic significance in AF patients. In addition to well-known risk factors, assessment of microvascular function can be a feasible approach for early prevention and a therapeutic target in AF patients.

Long-term outcomes of left atrial appendage closure with or without concomitant pulmonary vein isolation:a propensity score matching analysis based on CLACBAC study.

BACKGROUND: The combined procedure of left atrial appendage closure (LAAC) with concomitant pulmonary vein isolation (PVI) has demonstrated its efficacy and safety. However, there is still a lack of comparative investigations regarding the long-term benefits of the combined procedure when compared to LAAC alone. Our study aims to assess the long-term outcomes of combined procedure of LAAC with concomitant PVI in comparison with a propensity matched LAAC alone group. METHODS: Propensity score matching (PSM) was employed to rectify covariate imbalances, resulting in the inclusion of 153 comparable patients from the initial cohort of 333 non-valvular atrial fibrillation (AF) patients. Clinical outcomes, encompassing thrombotic events, major cardiocerebrovascular adverse events (MACCE), re-hospitalization due to cardiovascular disease (CVD), and atrial tachycardia (AT), were juxtaposed between the two groups. Bleeding events and peri-device complications, such as residual flow, device-related thrombus, and device replacement, were also compared. Additionally, a patients group underwent PVI alone was included for comparing AF recurrence rates between the PVI alone group and the combined group. RESULTS: Following PSM, 153 patients (mean age 70.3 ± 8.9, 62.7% men) were included, with 102 undergoing the combined procedure and 51 undergoing LAAC alone. No significant differences were found in baseline characteristics between the two groups. The mean follow-up time was 37.6 ± 7.9 months, and two patients were lost to follow-up in the combined procedure group. Thrombotic events were observed in 4 (7.8%) patients in the LAAC alone group and 4 (4.0%) in the combined group (Log-rank p = 0.301). The proportion of patients experiencing MACCE, re-hospitalization due to CVD, and AT between the two groups was comparable, as were bleeding events and peri-device complications. Among patients from the combined procedure group without AF recurrence, a significant difference was noted in prior-procedure left ventricular ejection fraction (LVEF) and LVEF at the 12th month after the procedure (57.2% ± 7.1% vs. 60.5% ± 6.5%, p = 0.002). CONCLUSION: The concomitant PVI and LAAC procedure did not increase procedure-related complications, nor did it confer significant benefits in preventing thrombotic events or reducing other cardiovascular events. However, the combined procedure improved heart function, suggesting potential long-term benefits.

Association of organ damage with predicted fat mass in a community-dwelling elderly: the Northern Shanghai study.

BACKGROUND: Body fat mass (FM) is associated with multiple organ damage. However, data regarding the relationship between various organ damage and FM are rare in the elderly. Therefore, we aim to perform an analysis on the relationship between organ damage and FM in a geriatric cohort. METHODS: 3331 participants were included in this analysis. Based on age, body height, body weight, waist circumference, and race, we calculated FM with the established formula. Organ damage, including arterial stiffening, lower extremity atherosclerosis, left ventricular hypertrophy (LVH), micro-albuminuria, and chronic kidney disease (CKD), were measured and calculated with standard methods. RESULTS: All organ damage parameters were significantly related to FM (all p < 0.001). In univariate logistics regression, the highest quartile of FM was tied to the increased risk of arterial stiffening, lower extremity atherosclerosis, LVH, micro-albuminuria, and CKD (all p < 0.05). After adjustment, participants with higher quantiles of FM had a significantly increased odd ratio (OR) for arterial stiffening [OR = 1.51, 95% confidence interval (CI): 1.15-1.99, p = 0.002] and LVH (OR = 1.99, 95% CI: 1.48-2.67, p < 0.001). Moreover, FM was linearly associated with arterial stiffening and LVH in total population and gender subgroups. Independent of confounders, FM was significantly correlated with arterial stiffening, lower extremity atherosclerosis, LVH and CKD in female, while was only related to LVH in male. CONCLUSIONS: Among various organ damage, elevated FM is significantly and independently associated with arterial stiffening and LVH in the elderly. Compared with men, women with increased FM are more likely to have multiple organ damage.

Prognostic Value of Angiography-Derived Index of Microcirculatory Resistance in Patients with Coronary Artery Disease Undergoing Rotational Atherectomy.

Background: Rotational atherectomy (RA) is the major tool used to treat severely calcified lesions in patients with coronary artery disease (CAD). The relationship between coronary microvascular dysfunction and RA remains unknown. Therefore, we attempted to explore the predictive implications of the coronary angiography-derived index of microcirculatory resistance (angio-IMR) in CAD patients undergoing RA. Methods: This retrospective study included 118 patients with severe coronary calcification who underwent a successful RA from January 2018 to June 2021. The angio-IMR was calculated based on computed flow and pressure dynamic principles to assess coronary microcirculatory function. Follow-up was performed on all patients for major adverse cardiovascular events (MACEs), including all-cause death, non-fatal myocardial infarction, target vessel revascularization (TVR), and stroke. Results: The mean angio-IMR for all patients was 25.58 ± 7.93. Patients were stratified the groups based on a mean angio-IMR of 25, fifty-four (45.8%) patients had angio-IMR ≥ 25. The logistic regression analysis showed that angiography-derived fractional flow reserve was significantly associated with coronary microvascular dysfunction. After median follow-up of 21.7 (15.1-24.0) months, MACEs occurred in 30.6%, including 12.5% all-cause deaths, 6.4% non-fatal myocardial infarction, 14.5% TVR, and 0.9% stroke. Kaplan-Meier analysis demonstrated that patients with angio-IMR ≥ 25 had greater cumulative MACEs (41.6%) and TVR (20.7%) than patients with preserved angio-IMR. COX regression analysis indicated that angio-IMR ≥ 25 and reduced left ventricular ejection fraction were independent predictors of MACEs. In addition, angio-IMR ≥ 25 and lowered minimum luminal area independently predicted TVR occurrence. Conclusions: In CAD patients undergoing RA, angio-IMR ≥ 25 was an independent and significant predictor of MACEs and TVR. Clinical Trial Registration: NCT05435898.

Algorithms of Electrocardiographic Changes for Quantitative and Localization Analysis of Thrombus Burden in Patients with Acute Pulmonary Thromboembolism.

Background: Various electrocardiographic (ECG) abnormalities are associated with the severity of pulmonary thromboembolism (PTE). The utility of evaluating the clot burden of PTE based on ECG findings alone has yet to be thoroughly investigated in Chinese patients. The aim of this study was therefore to use ECG signs to establish novel models for quantitative and localization analysis of clot burden in patients with acute PTE. Methods: Acute PTE patients from three centers were enrolled between 2015 and 2019 in a retrospective cohort study (NCT03802929). We analyzed the 12-lead ECGs at admission and studied computed tomography pulmonary angiography (CTPA) features to obtain the Qanadli score of clot burden and location of thrombus. Novel risk prediction models were developed and validated using derivation and external validation cohorts, respectively. Results: A total of 341 acute PTE patients were screened, of whom 246 (72.1%) were from Shanghai Tenth People's Hospital, 71 (20.8%) were from Shanghai Pulmonary Hospital and 24 (7.0%) were from Qidong People's Hospital. In the derivation cohort, predictors included in the final models were congestive heart failure, chronic obstructive pulmonary disease, hypertension, coronary heart disease, atrial fibrillation and ECG abnormalities. The CHARIS (COPD/CHF/CHD, HTN, Atrial arrhythmias/AF, RBBB/RAD, Inverted T wave and S1Q3T3/ Sinus tachycardia) I model was established for quantitatively assessing Qanadli score. It had moderate discrimination in both the derivation cohort (concordance index (c-index) of 0.720, 95% CI 0.655-0.780) and the validation cohort (c-index of 0.663, 95% CI 0.559-0.757). The CHARIS II model was used to predict the probability of trunk obstruction. It showed similar discrimination in the derivation cohort (c-index of 0.753, 95% CI 0.691-0.811) and in the validation cohort (c-index of 0.741, 95% CI 0.641-0.827). Calibration curves and Hosmer-Lemeshow test confirmed the accuracy of the risk prediction equations in the external validation dataset. Decision curve analysis showed the CHARIS I and CHARIS II algorithms had positive net benefits in both the derivation and validation cohorts. Conclusions: From quantitative and localization perspectives, the CHARIS algorithms can identify acute PTE patients with heavy thrombus burdens prior to imaging diagnosis. Clinical Trial Registration: NCT03802929, https://www.clinicaltrials.gov/study/NCT03802929.

Vasculopathy Augments Cardiovascular Risk in Community-Dwelling Elderly with Left Ventricular Hypertrophy.

This study aimed to investigate the impact of various vasculopathies alongside left ventricular hypertrophy (LVH) on cardiovascular risk in the elderly. This prospective cohort study included 3339 older adults from the Northern Shanghai Study, classified into four mutually exclusive left ventricular (LV) geometry groups based on echocardiographic data: normal geometry, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. Vasculopathy was categorized into three primary types: arteriosclerosis, atherosclerosis, and renal senescence. Major adverse cardiovascular events (MACEs) were defined as non-fatal acute myocardial infarction, non-fatal stroke, and cardiovascular deaths according to ICD-10 codes. Over a median follow-up period of 5.7 years, 221 incident cases of MACEs were identified. Concentric hypertrophy exhibited the highest prevalence of hypertension, the most significant increase in vascular stiffness, and the highest rate of MACEs. The adjusted Cox regression analysis showed that eccentric hypertrophy is associated with an increased risk of MACEs (HR: 1.638 [95% CI: 1.151-2.331], p = 0.006), while concentric hypertrophy shows an even higher risk (HR: 1.751 [95% CI: 1.127-2.721], p = 0.013). Conversely, concentric remodeling was not significantly associated with an increased risk of MACEs. Renal senescence presents a moderate but significant risk for MACEs, with an HR of 1.361 (95% CI: 1.019-1.819; p = 0.037) when adjusted for LVH. The Kaplan-Meier analysis showed that patients with LVH and multiple vasculopathies experience the most significant decrease in survival probability (log-rank p < 0.001). The subgroup analysis revealed that LVH significantly raises the risk of MACEs, especially in older males with hypertension, diabetes, or vasculopathy. This study reinforces the importance of LVH as a predictor of adverse cardiovascular outcomes and underscores the compounded risk associated with the presence of multiple vasculopathies. Additionally, it highlights renal senescence as a distinct and independent risk factor for MACEs, separate from LVH.

The Rehabilitation Efficacy of the Novel Metronomic Breathing Technique for Gerontic Patients After Percutaneous Coronary Intervention for Acute Myocardial Infarction-A Pilot Study.

Background: The respiratory rehabilitation technique is a crucial component of early cardiac recovery in geriatric patients with acute myocardial infarction (AMI). This study primarily investigated the effectiveness of a novel respiratory rehabilitation technique, metronomic breathing (MB), on geriatric patients after percutaneous coronary intervention for AMI and compliance with home-based rehabilitation compared to traditional respiratory rehabilitation. Methods: From June 2022 to March 2023, 75 acute myocardial infarction (AMI) patients admitted to the Shanghai Tenth People's Hospital Cardiovascular Department were consecutively enrolled. Ultimately, 46 patients completed the follow-up in this study-26 in the MB group and 20 in the control group-who underwent the novel MB technique and conventional abdominal breathing training. The primary endpoint of the study was left ventricular function measured by noninvasive hemodynamics three months after discharge. The secondary endpoints were compliance and quality of life after three months of home rehabilitation. Results: After the intervention, several cardiac functional parameters (SV, SVI, CO, CI, LCW, and LCWI), myocardial contractility parameters (VI), and systemic vascular resistance parameters (SVR and SVRI) were significantly greater in the MB group than in the preintervention group (P < 0.05). Furthermore, post-treatment, the MB group exhibited greater SV, SVI, CO, CI, and VI; lower SVR, SVRI, and SBP; and a lower readmission rate three months later than did the control group. The SF-36 scores after three months of MB intervention, PE, BP, GH, VT, SF, RE, and MH, were all significantly greater than those before treatment (P < 0.05). Moreover, the MB group displayed greater compliance with home-based cardiac rehabilitation (P < 0.05). Conclusion: Compared to conventional respiratory rehabilitation training methods, short-term metronomic respiratory therapy is more effective for reducing systemic vascular resistance, enhancing left ventricular ejection function, enhancing quality of life, and increasing home-based rehabilitation compliance in geriatric patients following AMI with PCI.

Cardiac cell senescence: molecular mechanisms, key proteins and therapeutic targets.

Cardiac aging, particularly cardiac cell senescence, is a natural process that occurs as we age. Heart function gradually declines in old age, leading to continuous heart failure, even in people without a prior history of heart disease. To address this issue and improve cardiac cell function, it is crucial to investigate the molecular mechanisms underlying cardiac senescence. This review summarizes the main mechanisms and key proteins involved in cardiac cell senescence. This review further discusses the molecular modulators of cellular senescence in aging hearts. Furthermore, the discussion will encompass comprehensive descriptions of the key drugs, modes of action and potential targets for intervention in cardiac senescence. By offering a fresh perspective and comprehensive insights into the molecular mechanisms of cardiac senescence, this review seeks to provide a fresh perspective and important theoretical foundations for the development of drugs targeting this condition.

Molecular classification and tumor microenvironment characteristics in pheochromocytomas.

Pheochromocytomas (PCCs) are rare neuroendocrine tumors that originate from chromaffin cells in the adrenal gland. However, the cellular molecular characteristics and immune microenvironment of PCCs are incompletely understood. Here, we performed single-cell RNA sequencing (scRNA-seq) on 16 tissues from 4 sporadic unclassified PCC patients and 1 hereditary PCC patient with Von Hippel-Lindau (VHL) syndrome. We found that intra-tumoral heterogeneity was less extensive than the inter-individual heterogeneity of PCCs. Further, the unclassified PCC patients were divided into two types, metabolism-type (marked by NDUFA4L2 and COX4I2) and kinase-type (marked by RET and PNMT), validated by immunohistochemical staining. Trajectory analysis of tumor evolution revealed that metabolism-type PCC cells display phenotype of consistently active metabolism and increased metastasis potential, while kinase-type PCC cells showed decreased epinephrine synthesis and neuron-like phenotypes. Cell-cell communication analysis showed activation of the annexin pathway and a strong inflammation reaction in metabolism-type PCCs and activation of FGF signaling in the kinase-type PCC. Although multispectral immunofluorescence staining showed a lack of CD8+ T cell infiltration in both metabolism-type and kinase-type PCCs, only the kinase-type PCC exhibited downregulation of HLA-I molecules that possibly regulated by RET, suggesting the potential of combined therapy with kinase inhibitors and immunotherapy for kinase-type PCCs; in contrast, the application of immunotherapy to metabolism-type PCCs (with antigen presentation ability) is likely unsuitable. Our study presents a single-cell transcriptomics-based molecular classification and microenvironment characterization of PCCs, providing clues for potential therapeutic strategies to treat PCCs.

The impact of contrast retention on thrombus formation risks in patients with atrial fibrillation: A numerical study.

Background: Contrast retention (CR) is an important predictor of left atrial appendage thrombus (LAAT) and stroke in patients with non-valvular atrial fibrillation (AF). We sought to explore the underlying mechanisms of CR using computational fluid dynamic (CFD) simulations. Methods: A total of 12 patients with AF who underwent both cardiac computed tomography angiography (CTA) and transesophageal echocardiography (TEE) before left atrial appendage occlusion (LAAO) were included in the study. The patients were allocated into the CR group or non-CR group based on left atrial appendage (LAA) angiography. Patient-specific models were reconstructed to evaluate time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and endothelial cell activation potential (ECAP). Additionally, the incidence of thrombosis was predicted using residence time (RT) at different time-points. Results: TAWSS was lower [median (Interquartile Range) 0.27 (0.19-0.47) vs 1.35 (0.92-1.79), p < 0.001] in LAA compared to left atrium. In contrast, RRT [1438 (409.70-13869) vs 2.23 (1.81-3.14), p < 0.001] and ECAP [122.70 (30.01-625.70) vs 0.19 (0.16-0.27), p < 0.001)] was higher in the LAA. The patients in the CR group had significantly higher RRT [(mean ± SD) 16274 ± 11797 vs 639.70 ± 595.20, p = 0.009] and ECAP [610.80 ± 365.30 vs 54.26 ± 54.38, p = 0.004] in the LAA compared to the non-CR group. Additionally, patients with CR had a wider range of thrombus-prone regions [0.44(0.27-0.66)% vs 0.05(0.03-0.27)%, p = 0.009] at the end of the 15th cardiac cycle. Conclusions: These findings suggest that CR might be an indicator of high-risk thrombus formation in the LAA. And CT-based CFD simulation may be a feasible substitute for the evaluation of LAA thrombotic risk in patients with AF, especially in patients with CR.

The correlation of atherogenic index of plasma with non-obstructive CAD and unfavorable prognosis among patients diagnosed with MINOCA.

BACKGROUND: The atherogenic index of plasma (AIP) is linked to lipid metabolism and has shown considerable prognostic value in cardiovascular disorders. However, its role in myocardial infarction with non-obstructive coronary arteries (MINOCA) has not been investigated. We assessed the relationship between AIP, the severity of coronary stenosis, and prognosis in MINOCA. METHODS: We included consecutive patients who were diagnosed with MINOCA. AIP was calculated using the base 10 logarithm of the ratio between the levels of TG and HDL-C. The patients were divided into four groups based on their AIP quartiles: Q1 (AIP<-0.145), Q2 (AIP≥-0.145and≤0.049), Q3 (AIP>0.049and≤0.253), and Q4 (AIP>0.253). All patients underwent follow-up for MACE. RESULTS: The final analysis included 421 patients, with 188 having normal coronaries (0 stenosis) and 233 exhibiting non-obstructive coronary artery disease (CAD) (<50 % stenosis). In the multivariate logistic analysis, highest AIP (Q4) group was significantly associated with increased risk of non-obstructive CAD in MINOCA (OR,1.994;95 % CI:1.075-3.698; P = 0.029). During the follow-up period, MACE occurred in 22.8 % of MINOCA patients. Q4 group exhibited a significantly higher rate of MACE (P = 0.021). Furthermore, when both AIP and coronary stenosis status were considered, the results revealed individuals in the Q4 group with non-obstructive CAD had the highest risk of MACE (log-rank P = 0.027). The adjusted Cox analysis indicated that the Q4 group was associated with a 2.052-fold increase in the HR of MACE. CONCLUSION: AIP exhibits a notable association with the incidence of MACE in MINOCA patients and serves as a substantial marker for non-obstructive CAD in this patient group.

Identification of a Hippocampus-to-Zona Incerta Projection involved in Motor Learning.

Motor learning (ML), which plays a fundamental role in growth and physical rehabilitation, involves different stages of learning and memory processes through different brain regions. However, the neural mechanisms that underlie ML are not sufficiently understood. Here, a previously unreported neuronal projection from the dorsal hippocampus (dHPC) to the zona incerta (ZI) involved in the regulation of ML behaviors is identified. Using recombinant adeno-associated virus, the projections to the ZI are surprisingly identified as originating from the dorsal dentate gyrus (DG) and CA1 subregions of the dHPC. Furthermore, projection-specific chemogenetic and optogenetic manipulation reveals that the projections from the dorsal CA1 to the ZI play key roles in the acquisition and consolidation of ML behaviors, whereas the projections from the dorsal DG to the ZI mediate the retrieval/retention of ML behaviors. The results reveal new projections from the dorsal DG and dorsal CA1 to the ZI involved in the regulation of ML and provide insight into the stages over which this regulation occurs.

Association of liver fibrosis-4 index with adverse outcomes in hypertrophic cardiomyopathy patients.

AIMS: The fibrosis-4 index (FIB-4) is a non-invasive tool to assess fibrosis risk in chronic liver disease. We aimed to explore the relationship between the FIB-4 index and long-term major adverse cardiovascular events (MACE) in HCM patients. METHODS AND RESULTS: Consecutive patients diagnosed with HCM were included. Patients were divided into two groups using a defined cutoff value established through a ROC analysis for predicting MACE (FIB-4 ≥ 2.37 and FIB-4 < 2.37). The final analysis comprised 187 HCM patients (34.8% females, 66.49 ± 11.43 years of age), with 47 (25.1%) in the FIB-4 ≥ 2.37 group and 140 (74.9%) in the FIB-4 < 2.37 group. Among these, 147 (78.6%) individuals had complete follow-up data. Patients with FIB-4 ≥ 2.37 demonstrated a higher prevalence of co-morbidities such as atrial fibrillation (27.7% vs. 7.9%; P < 0.001), heart failure (55.3% vs. 24.3%; P < 0.001), elevated NT-proBNP levels (3.03 ± 4.74 vs. 0.66 ± 1.08; P < 0.001), and lower LVEF (58.51 ± 7.86 vs. 61.84 ± 5.04; P = 0.001). Over a median of 41 (IQR 16-63) months follow-up, MACE occurred in 49 (33.3%), with a significantly higher incidence in the FIB-4 ≥ 2.37 group (58.8% vs. 25.7%, P < 0.001). Cardiac death rates were also elevated in the FIB-4 ≥ 2.37 group (20.6% vs. 2.7%, P = 0.001). Cox regression analysis revealed an independent association between FIB-4 ≥ 2.37 and a higher risk of MACE (adjusted HR: 1.919, 95% CI 1.015-3.630; P = 0.045) and cardiac death (adjusted HR: 9.518, 95% CI 1.718-52.732; P = 0.010). Furthermore, the FIB-4 index shows positive correlations with left atrium diameter (r = 0.229; P = 0.003), septal thickness (r = 0.231; P = 0.002), posterior wall thickness (r = 0.235; P = 0.001), and NT-proBNP (r = 0.271; P < 0.001). Conversely, a negative correlation was observed between the FIB-4 index and left ventricular ejection fraction (r = -0.185; P = 0.011). CONCLUSION: Elevated FIB-4 index, indicative of liver fibrosis, is independently associated with an increased risk of long-term MACE in HCM patients. This emphasizes the potential influence of liver function abnormalities on HCM prognosis, underscoring the need for comprehensive risk assessment in clinical management.

Metabolomic landscape of renal cell carcinoma in von Hippel-Lindau syndrome in a Chinese cohort.

Von Hippel-Lindau (VHL) syndrome is a rare autosomal dominant disorder, where renal cell carcinoma (RCC) serves as a significant cause of mortality. We collected peripheral blood from 61 VHL-RCC patients and 31 healthy individuals, along with 19 paired RCC tumor and adjacent non-malignant samples. Using liquid chromatography-mass spectrometry, we identified 238 plasma and 241 tissue differentially abundant metabolites (DAMs), highlighting key pathways such as arginine and proline metabolism. The top 10 of the 23 DAMs, common to both plasma and tissue, were instrumental in constructing a high-performance diagnostic model. These DAMs demonstrated significant correlations with VHL gene mutation types. Cox regression analysis revealed that plasma levels of N2,N2-dimethylguanosine were associated with the timing of RCC onset in VHL patients, acting as an independent predictive factor. This study enhances diagnostic accuracy for this rare condition and opens new avenues for exploring metabolic mechanisms of the disease and potential therapeutic directions.

The burden and management competency of cardiomyopathies in China: a nationwide survey study.

Background: The public health burden of cardiomyopathies and competency in their management by health agencies in China are not well understood. Methods: This study adopted a multi-stage sampling method for hospital selection. In the first stage, nationwide tertiary hospital recruitment was performed. As a result, 88 hospitals with the consent of the director of cardiology and access to an established electronic medical records system, were recruited. In the second stage, we sampled 66 hospitals within each geographic-economic stratification through a random sampling process. Data on (1) the outpatient and inpatient visits for cardiomyopathies between 2017 and 2021 and (2) the competency in the management of patients with cardiomyopathies, were collected. The competency of a hospital to provide cardiomyopathy care was evaluated using a specifically devised scale. Findings: The outpatient and inpatient visits for cardiomyopathies increased between 2017 and 2021 by 38.6% and 33.0%, respectively. Most hospitals had basic facilities for cardiomyopathy assessment. However, access to more complex procedures was limited, and the integrated management pathway needs improvement. Only 4 (6.1%) of the 66 participating hospitals met the criteria for being designated as a comprehensive cardiomyopathy center, and only 29 (43.9%) could be classified as a primary cardiomyopathy center. There were significant variations in competency between hospitals with different administrative and economic levels. Interpretation: The health burden of cardiomyopathies has increased significantly between 2017 and 2021 in China. Although most tertiary hospitals in China can offer basic cardiomyopathy care, more advanced facilities are not yet universally available. Moreover, inconsistencies in the management of cardiomyopathies across hospitals due to differing administrative and economic levels warrants a review of the nation allocation of medical resources. Funding: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2023-I2M-1-001) and the National High Level Hospital Clinical Research Funding (2022-GSP-GG-17).

Efficacy and safety of olmesartan medoxomil­amlodipine besylate tablets (Sevikar®) in older patients with essential hypertension: Subgroup analysis from the Sevikar study.

Essential hypertension is a notable threat for the older (age, ≥65 years) population. However, to the best of our knowledge, a real-world study assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablets in older Chinese patients with essential hypertension has not been performed. Therefore, the present study aimed to evaluate the efficacy and safety of OM-AML tablets in these patients. A total of 463 older Chinese patients with essential hypertension treated with OM-AML (20/5 mg) tablets (Sevikar®) were analyzed in a prospective, single-arm, multi-center, real-world study. Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, and at week (W)4 and W8 after OM-AML tablet administration were measured. The mean ± standard error change of SeSBP/SeDBP was -10.3±0.8/-4.6±0.5 and -12.5±0.8/-5.6±0.5 mmHg at W4 and W8, respectively. At W4, 74.1 and 26.8% of patients achieved BP target according to the China and American Heart Association (AHA) criteria, while at W8, 78.0 and 38.7% of patients reached these BP targets accordingly. Finally, 76.5 and 80.5% of patients achieved BP response at W4 and W8, respectively. Furthermore, home-measured SeSBP and SeDBP were significantly decreased from W1 to W8 (both P<0.001). Additionally, the satisfaction of both patients and physicians was elevated at W8 compared with at W0 (both P<0.001). The medication possession rate from baseline to W4 and W8 was 95.5 and 92.5%. The most common drug-associated adverse events by system organ classes were nervous system disorder (4.5%), vascular disorder (2.8%), and general disorder and administration site conditions (2.6%), which were generally mild. In conclusion, OM-AML tablets may be considered effective and safe in lowering BP, enabling the achievement of guideline-recommended BP targets in older Chinese patients with essential hypertension.

Design and Rationale of Targeted Therapy With a Sirolimus-Eluting, Biodegradable Polymer Coronary Stent in Chronic Total Occlusions (TARGET CTO): A Multicenter, Open-Label, Randomized Noninferiority Trial.

Background: Treatment of chronic total occlusions (CTOs) is referred to as the last frontier of percutaneous coronary interventions and is currently performed in 10% to 20% of procedures. Improved outcomes with newer generation drug-eluting stents require further research. Methods: The TARGET CTO trial (NCT03040934) is a prospective, multicenter, randomized, noninferiority trial that plans to randomize 196 subjects (1:1) to either a newer-generation sirolimus target-eluting stent or an everolimus-eluting stent. Patients are candidates if they present with at least 1 CTO lesion in a native coronary artery with a diameter of ≥2.50 mm to ≤4.00 mm and a length of <100 mm. In addition, 44 subjects will participate in an optical coherence tomography (OCT) substudy. Clinical follow-up is planned up to 5 years after stent implantation. Angiographic follow-up is planned at 12 months, whereas OCT will be obtained after the procedure, at 3 and 12 months. The primary end point is in-stent late lumen loss by quantitative coronary angiography at 12 months. The key secondary end point is neointimal thickness by OCT at 3 months. Imaging end points are assessed by an independent core lab. Clinical end points are adjudicated by an independent clinical events committee. Conclusion: The TARGET CTO trial compares a sirolimus target-eluting stent with an everolimus-eluting stent for management of CTOs according to contemporary interventional practices. The primary angiographic end points will be reported at 12 months and clinical follow-up will continue for up to 5 years.