胡盛寿
中国医学科学院阜外医院 成人外科中心
OBJECTIVE:Daytime napping has been reported to have a potential association with an increased risk of cardiovascular diseases (CVDs) in several cohort studies, but the causal effects are unclear. In this study, we aimed to investigate the relationship between daytime napping and CVDs, as well as to validate causality in this relationship by Mendelian randomization (MR).METHODS:A two-sample MR method was used to evaluate the causal effect of daytime napping on CVDs. The exposure of daytime napping was extracted from publicly available genome-wide association studies (GWASs) in the UK Biobank, and the outcomes of 14 CVDs were obtained from the FinnGen consortium. A total of 49 single-nucleotide polymorphisms (SNPs) were used as the instrumental variables. The effect estimates were calculated by using the inverse-variance weighted method.RESULTS:The MR analyses showed that genetically predicted daytime napping was associated with an increased risk of five CVDs, including heart failure (odds ratio (OR): 1.71, 95% CI: 1.19-2.44, p = 0.003), hypertension (OR: 1.51, 95% CI: 1.05-2.16, p = 0.026), atrial fibrillation (OR: 1.71, 95% CI: 1.02-2.88, p = 0.042), cardiac arrythmias (OR: 1.47, 95% CI: 1.47, 95% CI: 1.01-2.13, p = 0.042) and coronary atherosclerosis (OR: 1.77, 95% CI: 1.17-2.68, p = 0.006). No significant influence was observed for other CVDs.CONCLUSION:This two-sample MR analysis suggested that daytime napping was causally associated with an increased risk of heart failure, hypertension, atrial fibrillation, cardiac arrythmias and coronary atherosclerosis.
Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese 2024
Cardiac hypertrophy can develop to end-stage heart failure (HF), which inevitably leading to heart transplantation or death. Preserving cardiac function in cardiomyocytes (CMs) is essential for improving prognosis in hypertrophic cardiomyopathy (HCM) patients. Therefore, understanding transcriptomic heterogeneity of CMs in HCM would be indispensable to aid potential therapeutic targets investigation. We isolated primary CM from HCM patients who had extended septal myectomy, and obtained transcriptomes in 338 human primary CM with single-cell tagged reverse transcription (STRT-seq) approach. Our results revealed that CMs could be categorized into three subsets in nonfailing HCM heart: high energy synthesis cluster, high cellular metabolism cluster and intermediate cluster. The expression of electron transport chain (ETC) was up-regulated in larger-sized CMs from high energy synthesis cluster. Of note, we found the expression of Cytochrome c oxidase subunit 7B (COX7B), a subunit of Complex IV in ETC had trends of positively correlation with CMs size. Further, by assessing COX7B expression in HCM patients, we speculated that COX7B was compensatory up-regulated at early-stage but down-regulated in failing HCM heart. To test the hypothesis that COX7B might participate both in hypertrophy and HF progression, we used adeno associated virus 9 (AAV9) to mediate the expression of Cox7b in pressure overload-induced mice. Mice in vivo data supported that knockdown of Cox7b would accelerate HF and Cox7b overexpression could restore partial cardiac function in hypertrophy. Our result highlights targeting COX7B and preserving energy synthesis in hypertrophic CMs could be a promising translational direction for HF therapeutic strategy.
Journal of molecular and cellular cardiology 2024
The Annual Report on Cardiovascular Health and Diseases in China (2022) intricate landscape of cardiovascular health in China. This is the first section of the report, which dissects influential factors across diverse domains. The investigation identifies tobacco use as a paramount concern, portraying China as the global epicenter of tobacco consumption. Cigarette smoking, exacerbated by second-hand smoke exposure, emerges as a critical and preventable risk factor, contributing to a surge in attributable deaths over the past three decades. In the realm of dietary nutrition, the study discerns an overall improvement, yet discerns worrisome deviations, notably an escalating fat intake surpassing recommended guidelines. The shifting dietary structure reveals diminished consumption of cereals and vegetables juxtaposed with an uptick in animal foods, while excessive intake of cooking oil and salt persists, straying substantially from endorsed levels. The exploration of physical activity patterns unfolds a nuanced narrative. Varied trends are observed among students, with concerns arising from sedentary behaviors and inadequate adherence to recommended guidelines. The analysis spans a trajectory of declining physical activity in Chinese adults, coupled with an alarming surge in sedentary leisure time, ultimately linking these factors to heightened risks of cardiovascular diseases and increased adiposity. An examination of overweight and obesity trends uncovers a relentless upward trajectory, projecting substantial prevalence by 2030. Noteworthy prevalence rates underscore the imperative for targeted interventions to curtail this burgeoning health crisis, with the anticipated prevalence extending to nearly two-thirds of the adult population. Psychological factors, notably depression, constitute an integral facet of cardiovascular health. Prevalence rates among patients with coronary artery disease and acute myocardial infarction underscore the intricate interplay between mental health and cardiovascular outcomes. Additionally, persistent depressive symptoms are shown to significantly elevate the risk of cardiovascular diseases and mortality. This first section underscores the multifaceted challenges facing cardiovascular health in China, emphasizing the imperative for tailored interventions across tobacco control, dietary habits, physical activity, obesity management, and psychological well-being to mitigate the escalating burden of cardiovascular diseases in the population.
Journal of geriatric cardiology : JGC 2024
BACKGROUND:Dilation may be the first right ventricular change and accelerates the progression of threatening ventricular tachyarrhythmias and heart failure for patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), but the treatment for right ventricular dilation remains limited.METHODS:Single-cell RNA sequencing (scRNA-seq) of blood and biventricular myocardium from 8 study participants was performed, including 6 end-stage heart failure patients with ARVC and 2 normal controls. ScRNA-seq data was then deeply analyzed, including cluster annotation, cellular proportion calculation, and characterization of cellular developmental trajectories and interactions. An integrative analysis of our single-cell data and published genome-wide association study-based data provided insights into the cell-specific contributions to the cardiac arrhythmia phenotype of ARVC. Desmoglein 2 (Dsg2)mut/mut mice were used as the ARVC model to verify the therapeutic effects of pharmacological intervention on identified cellular cluster.RESULTS:Right ventricle of ARVC was enriched of CCL3+ proinflammatory macrophages and TNMD+ fibroblasts. Fibroblasts were preferentially affected in ARVC and perturbations associated with ARVC overlap with those reside in genetic variants associated with cardiac arrhythmia. Proinflammatory macrophages strongly interact with fibroblast. Pharmacological inhibition of Nod-like receptor protein 3 (NLRP3), a transcriptional factor predominantly expressed by the CCL3+ proinflammatory macrophages and several other myeloid subclusters, could significantly alleviate right ventricular dilation and dysfunction in Dsg2mut/mut mice (an ARVC mouse model).CONCLUSIONS:This study provided a comprehensive analysis of the lineage-specific changes in the blood and myocardium from ARVC patients at a single-cell resolution. Pharmacological inhibition of NLRP3 could prevent right ventricular dilation and dysfunction of mice with ARVC.
BMC medicine 2024
OBJECTIVE:Quantitative flow ratio (QFR) is a novel noninvasive tool for the functional assessment of coronary stenosis. Whether or not QFR could predict graft outcomes after coronary artery bypass grafting procedure is unknown. This study aimed to investigate the association of QFR value with graft outcomes after coronary artery bypass grafting surgery.METHODS:The QFR values were retrospectively obtained from patients receiving coronary artery bypass grafting surgery from 2017 to 2019 in the Graft Patency Between No-Touch Vein Harvesting Technique and Conventional Approach in Coronary Artery Bypass Graft Surgery (PATENCY) trial. QFR calculation was conducted in eligible coronary arteries, defined as those with ≥50% stenosis and a diameter ≥1.5 mm. A threshold of QFR ≤0.80 was considered functionally significant stenosis. The primary outcome was graft occlusion at 12 months evaluated by computed tomography angiography.RESULTS:Two thousand twenty-four patients with 7432 grafts (2307 arterial grafts and 5125 vein grafts) were included. For the arterial grafts, the risk of 12-month occlusion was significantly increased in the QFR >0.80 group than in the QFR ≤0.80 group (7.1% vs 2.6%; P = .001; unadjusted model: odds ratio, 3.08; 95% CI, 1.65-5.75; fully adjusted model: odds ratio, 2.67; 95% CI, 1.44-4.97). No significant association was observed in the vein grafts (4.6% vs 4.3%; P = .67; unadjusted model: odds ratio, 1.10; 95% CI, 0.82-1.47; fully adjusted model: odds ratio, 1.12; 95% CI, 0.83-1.51). Results were stable across sensitivity analyses with a QFR threshold of 0.78 and 0.75.CONCLUSIONS:Target vessel QFR >0.80 was associated with a significantly higher risk of arterial graft occlusion at 12 months after coronary artery bypass grafting surgery. No significant association was found between target lesion QFR and vein graft occlusion.
The Journal of thoracic and cardiovascular surgery 2023
Tissue slicing-assisted digestion (TSAD) of adult cardiomyocytes has shown significant improvements over conventional chunk methods. However, it remains unclear how this method compares to Langendorff perfusion, the current standard of adult cardiomyocyte isolation. Using adult Bama minipigs, we performed cardiomyocyte isolation via these two distinct methods, and compared the resulting cellular quality, including viability, cellular structure, gene expression, and electrophysiological properties, of cardiomyocytes from 3 distinct anatomical regions, namely the left ventricle, right ventricle, and left atrial appendage. Our results revealed largely indistinguishable cell quality in all of the measured parameters. These findings suggest that that TSAD can be reliably used to isolate adult mammalian cardiomyocytes as a reliable alternative to perfusion in cardiomyocyte isolation from larger mammals, particularly when Langendorff perfusion is not feasible.
PloS one 2023
Heart failure (HF), leading as one of the main causes of mortality, has become a serious public health issue with high prevalence around the world. Single cardiomyocyte (CM) metabolomics promises to revolutionize the understanding of HF pathogenesis since the metabolic remodeling in the human hearts plays a vital role in the disease progression. Unfortunately, current metabolic analysis is often limited by the dynamic features of metabolites and the critical needs for high-quality isolated CMs. Here, high-quality CMs were directly isolated from transgenic HF mice biopsies and further employed in the cellular metabolic analysis. The lipids landscape in individual CMs was profiled with a delayed extraction mode in time-of-flight secondary ion mass spectrometry. Specific metabolic signatures were identified to distinguish HF CMs from the control subjects, presenting as possible single-cell biomarkers. The spatial distributions of these signatures were imaged in single cells, and those were further found to be strongly associated with lipoprotein metabolism, transmembrane transport, and signal transduction. Taken together, we systematically studied the lipid metabolism of single CMs with a mass spectrometry imaging method, which directly benefited the identification of HF-associated signatures and a deeper understanding of HF-related metabolic pathways.
Research (Washington, D.C.) 2023
Hypertrophic cardiomyopathy (HCM) is the most common cardiac genetic disorder characterized by cardiomyocyte hypertrophy and cardiac fibrosis. Pathological cardiac remodeling in the myocardium of HCM patients may progress to heart failure. An in-depth elucidation of the lineage-specific changes in pathological cardiac remodeling of HCM is pivotal for the development of therapies to mitigate the progression. Here, we performed single-nucleus RNA-seq of the cardiac tissues from HCM patients or healthy donors and conducted spatial transcriptomic assays on tissue sections from patients. Unbiased clustering of 55,122 nuclei from HCM and healthy conditions revealed 9 cell lineages and 28 clusters. Lineage-specific changes in gene expression, subpopulation composition, and intercellular communication in HCM were discovered through comparative analyses. According to the results of pseudotime ordering, differential expression analysis, and differential regulatory network analysis, potential key genes during the transition towards a failing state of cardiomyocytes such as FGF12, IL31RA, and CREB5 were identified. Transcriptomic dynamics underlying cardiac fibroblast activation were also uncovered, and potential key genes involved in cardiac fibrosis were obtained such as AEBP1, RUNX1, MEOX1, LEF1, and NRXN3. Using the spatial transcriptomic data, spatial activity patterns of the candidate genes, pathways, and subpopulations were confirmed on patient tissue sections. Moreover, we showed experimental evidence that in vitro knockdown of AEBP1 could promote the activation of human cardiac fibroblasts, and overexpression of AEBP1 could attenuate the TGFβ-induced activation. Our study provided a comprehensive analysis of the lineage-specific regulatory changes in HCM, which laid the foundation for targeted drug development in HCM.
Cell discovery 2023
OBJECTIVES:Acknowledging lacking of consensus exist in total aortic arch (TAA) surgery for acute type A aortic dissection (AAD), this study aimed to investigate the neurologic injury rate between bilateral and unilateral cerebrum perfusion on the specific population.METHODS:A total of 595 AAD patients other than Marfan syndrome receiving TAA surgery since March 2013 to March 2022 were included. Among them, 276 received unilateral cerebral perfusion (via right axillary artery, RCP) and 319 for bilateral cerebral perfusion (BCP). The primary outcome was neurologic injury rate. Secondary outcomes were 30-day mortality, serum inflammation response (high sensitivity C reaction protein, hs-CRP; Interleukin-6, IL-6; cold-inducible RNA binding protein, CIRBP) and neuroprotection (RNA-binding motif 3, RBM3) indexes.RESULTS:The BCP group reported a significantly lower permanent neurologic deficits [odds ratio: 0.481, Confidence interval (CI): 0.296-0.782, p = 0.003] and 30-day mortality (odds ratio: 0.353, CI: 0.194-0.640, p < 0.001) than those received RCP treatment. There were also lower inflammation cytokines (hr-CRP: 114 ± 17 vs. 101 ± 16 mg/L; IL-6: 130 [103,170] vs. 81 [69,99] pg/ml; CIRBP: 1076 [889, 1296] vs. 854 [774, 991] pg/ml, all p < 0.001), but a higher neuroprotective cytokine (RBM3: 4381 ± 1362 vs 2445 ± 1008 pg/mL, p < 0.001) at 24 h after procedure in BCP group. Meanwhile, BCP resulted in a significantly lower Acute Physiology, Age and Chronic Health Evaluation (APACHE) Ⅱscore (18 ± 6 vs 17 ± 6, p < 0.001) and short stay in intensive care unit (4 [3,5] vs. 3 [2,3] days, p < 0.001) and hospital (16 ± 4 vs 14 ± 3 days, p < 0.001).CONCLUSIONS:This present study indicated that BCP compared with RCP was associated with lower permanent neurologic deficits and 30-day mortality in AAD patients other than Marfan syndrome receiving TAA surgery.
Perfusion 2023
OBJECTIVES:For transposition of the great arteries with unrestricted ventricular septal defect and pulmonary stenosis, double-root translocation is reported to reconstruct ideal double artery roots with growth potential. However, prospective long-term studies describing the long-term outcomes are still scarce. Therefore, the aim was to assess development of double artery roots, hemodynamics, and freedom from death and heart failure 17 years after double-root translocation, Rastelli, and Réparation à l'Etage Ventriculaire procedures.METHODS:In this prospective population-based study, 266 patients with transposition of the great arteries/ventricular septal defect/pulmonary stenosis (from July 2004 to August 2021) were consecutively included before surgery. All patients were divided into 3 groups based on the type of operation: double-root translocation (174), Rastelli (68), and Réparation à l'Etage Ventriculaire (24), who accepted postoperative evaluations annually. Generalized linear mixed model analysis was performed to determine growth potential of artery roots.RESULTS:Longitudinal repeated computed tomography measurements show the pulmonary root has significantly increased diameter (0.62 [0.03] mm/y, P < .001) over time and an adequate Z-score (-0.18) at the last follow-up only in the double-root translocation group. The pressure gradients of double outflow tracts in the double-root translocation group were the least among 3 groups. The probabilities of freedom from death/heart failure at the 15th year were 73.1%, 59.3%, and 60.9% in the double-root translocation, Rastelli, and Réparation à l'Etage Ventriculaire groups, respectively (double-root translocation vs Rastelli, P = .026; double-root translocation vs Réparation à l'Etage Ventriculaire, P = .009; Rastelli vs Réparation à l'Etage Ventriculaire, P = .449).CONCLUSIONS:By reconstructing ideal double artery roots, double-root translocation can provide postoperative long-term excellent hemodynamics and minimal death and heart failure for patients with transposition of the great arteries/ventricular septal defect/pulmonary stenosis.
The Journal of thoracic and cardiovascular surgery 2023
