崔存英
河南省人民医院 超声科
Pulmonary atresia (PA) is a severe cyanotic congenital heart disease. Although some genetic mutations have been described to be associated with PA, the knowledge of pathogenesis is insufficient. The aim of this research was to use whole-exome sequencing (WES) to determine novel rare genetic variants in PA patients. We performed WES in 33 patients (27 patient-parent trios and 6 single probands) and 300 healthy control individuals. By applying an enhanced analytical framework to incorporate de novo and case-control rare variation, we identified 176 risk genes (100 de novo variants and 87 rare variants). Protein‒protein interaction (PPI) analysis and Genotype-Tissue Expression analysis revealed that 35 putative candidate genes had PPIs with known PA genes with high expression in the human heart. Expression quantitative trait loci analysis revealed that 27 genes that were identified as novel PA genes that could be affected by the surrounding single nucleotide polymorphism were screened. Furthermore, we screened rare damaging variants with a threshold of minor allele frequency at 0.5% in the ExAC_EAS and GnomAD_exome_EAS databases, and the deleteriousness was predicted by bioinformatics tools. For the first time, 18 rare variants in 11 new candidate genes have been identified that may play a role in the pathogenesis of PA. Our research provides new insights into the pathogenesis of PA and helps to identify the critical genes for PA.
Open life sciences 2023
Objectives:To assess the mid-term safety and efficacy of transthoracic perimembranous ventricular septal defect (Pm-VSD) closure using a new biodegradable device. Implantation entailed right subaxillary minithoracotomy under transesophageal echocardiography guidance.Methods:Between October 2019 and January 2020, 13 patients (males, 5; mean age, 3.6 ± 2.5 years) with Pm-VSDs underwent transthoracic device closures at Zhengzhou University Central China Fuwai Hospital as described previously. Delivery pathways were established by manipulating a hollow probe from right atrium through tricuspid valve to right ventricle and then through VSDs to left ventricle, whereupon installation took place.Results:All occluder implantations were successfully executed. Mean defect size was 4.1 ± 1.0 mm, and mean device waist size was 5.2 ± 1.1 mm. One patient (7.7%) with 1.5-mm residual shunt showed complete closure at discharge. There was 1 instance of postoperative incomplete right bundle branch block, which converted to complete right bundle branch block at month 1. During patient follow-up (mean, 24.6 ± 0.8 months), no device dislocations, new residual shunts, new valvular regurgitation, or detectable atrioventricular block ensued.Conclusions:Closure of Pm-VSDs using a novel, fully biodegradable occluder in the manner described has proven safe and effective at mid-term follow-up. Long-term safety and efficacy of this device must be further corroborated in a large patient cohort going forward.
JTCVS techniques 2023
Background:Hypertension (HT) and obesity often coexist and contribute to left atrial (LA) dysfunction. The present study aimed to compare LA function in hypertensive individuals and control participants with different body mass index (BMI) categories and to explore whether there is an interaction effect between HT and obesity on LA function.Methods:In this cross-sectional study, a total of 258 individuals (145 hypertensive and 113 non-hypertensive patients) were prospectively enrolled from Fuwai Central China Cardiovascular Hospital from September 2020 to November 2021. Hypertensive and non-hypertensive patients were both divided into three study subgroups (n=35 per group) according to their BMI: normal weight (BMI 18.5-<25 kg/m2), overweight (BMI 25-<30 kg/m2), and obesity (BMI ≥30 kg/m2) groups. LA volume and strain parameters were obtained using three-dimensional echocardiography.Results:A significant interaction effect between HT and obesity on LA function was observed [PInteraction =0.04, 0.03, 0.005, 0.01, and 0.002 for LA ejection fraction (LAEF), LA passive ejection fraction (LAPEF), LA active ejection fraction (LAAEF), LA reservoir longitudinal strain (LASr), and LA contraction longitudinal strain (LASct), respectively; PInteraction <0.001 for LA conduit longitudinal strain (LAScd)]. Univariate correlation analysis revealed that HT [LASr, r=-0.53, 95% confidence interval (CI): -0.62 to -0.42, P<0.001; LAScd, r=-0.49, 95% CI: -0.58 to -0.39, P<0.001; and LASct, r=-0.46, 95% CI: -0.55 to -0.34, P<0.001] and BMI categories (LASr, r=-0.68, 95% CI: -0.75 to -0.61, P<0.001; LAScd, r=-0.47, 95% CI: -0.57 to -0.35, P<0.001; and LASct, r=-0.73, 95% CI: -0.78 to -0.66, P<0.001) were negatively correlated with LA strains. A generalized linear model further demonstrated that there was an interaction effect between HT and obesity on LA strains after adjusting for confounding factors (Model 2: LASr, βHT*Obesity =-1.91, 95% CI: -3.48 to -0.35, P=0.01; LAScd, βHT*Obesity =-3.26, 95% CI: -4.83 to -1.70, P<0.001; LASct, βHT*Overweight =-1.97, 95% CI: -3.03 to -0.91, P<0.001; βHT*Obesity =-1.54, 95% CI: -2.67 to -0.41, P=0.007).Conclusions:Both HT and increasing BMI category had an adverse effect on LA function. The coexistence of HT and obesity further impaired LA performance in an interaction manner. Weight loss is essential to reduce the incidence of adverse cardiovascular events in hypertensive patients.
Quantitative imaging in medicine and surgery 2023
Background:Type 2 diabetes mellitus (T2DM) and hypertension (HT) often coexist and contribute to left atrial (LA) functional abnormalities. The aim of the present study was to explore whether there is a potential interaction effect between T2DM and HT on LA function.Methods:A total of 135 patients (45 with T2DM only, 45 with HT only, and 45 with both T2DM and HT) were enrolled and compared to 45 age- and sex-matched controls. LA volume fraction, including LA ejection fraction (LAEF), LA expansion index (LAEI), LA passive emptying fraction (LAPEF), and LA active emptying fraction (LAAEF), and strain parameters, including LA reservoir longitudinal strain (LASr), LA conduit longitudinal strain (LAScd), and LA contraction longitudinal strain (LASct), were obtained using three-dimensional echocardiography (3DE).Results:Patients with T2DM had significantly more impaired LA reservoir and conduit functions compared to those without T2DM (P<0.05), and patients with HT had a significantly more impaired LA reservoir function, conduit function, and booster pump function compared to those without HT (P<0.05). Two-way analysis of variance showed that there were significant additive interaction effects between T2DM and HT with respect to LASr (PT2DM + HT =0.002) and LAScd (PT2DM + HT =0.001). Generalized linear model demonstrated that T2DM + HT had a greater relative contribution than either T2DM or HT alone to the LA strain indexes, even after adjustment for other confounders (LASr, βT2DM + HT =-3.931, 95% CI: -6.237 to -1.624, P=0.001; LAScd, βT2DM + HT=-3.781, 95% CI: -5.653 to -1.908, P<0.001).Conclusions:Both T2DM and HT had an adverse effect on LA function. The coexistence of both conditions further impaired LA performance in an additive interaction fashion.
Quantitative imaging in medicine and surgery 2023
BACKGROUND:Cardiac-resident or -enriched microRNAs (miRNAs) could be released into the bloodstream becoming circulating cardiac miRNAs, which are increasingly recognized as non-invasive and accessible biomarkers of multiple heart diseases. However, dilated cardiomyopathy (DCM)-associated circulating miRNAs (DACMs) and their roles in DCM pathogenesis remain largely unexplored.METHODS:Two human cohorts, consisting of healthy individuals and DCM patients, were enrolled for serum miRNA sequencing (10 vs. 10) and quantitative polymerase chain reaction validation (46 vs. 54), respectively. Rigorous screening strategy was enacted to define DACMs and their potentials for diagnosis. DCM mouse model, different sources of cardiomyocytes, adeno-associated virus 9 (AAV9), gene knockout, RNAscope miRNA in situ hybridization, mRFP-GFP-LC3B reporter, echocardiography and transmission electron microscopy were adopted for mechanistic explorations.RESULTS:Serum miRNA sequencing revealed a unique expression pattern for DCM circulating miRNAs. DACMs miR-26a-5p, miR-30c-5p, miR-126-5p and miR-126-3p were found to be depleted in DCM circulation as well as heart tissues. Their expressions in circulation and heart tissues were proven to be correlated significantly, and a combination of these miRNAs was suggested potential values for DCM diagnosis. FOXO3, a predicted common target, was experimentally demonstrated to be co-repressed within cardiomyocytes by these DACMs except miR-26a-5p. Delivery of a combination of miR-30c-5p, miR-126-5p and miR-126-3p into the murine myocardium via AAV9 carrying an expression cassette driven by cTnT promoter, or cardiac-specific knockout of FOXO3 (Myh6-CreERT2 , FOXO3 flox+/+ ) dramatically attenuated cardiac apoptosis and autophagy involved in DCM progression. Moreover, competitively disrupting the interplay between DACMs and FOXO3 mRNA by specifically introducing their interacting regions into murine myocardium crippled the cardioprotection of DACMs against DCM.CONCLUSIONS:Circulating cardiac miRNA-FOXO3 axis plays a pivotal role in safeguarding against myocardial apoptosis and excessive autophagy in DCM development, which may provide serological cues for DCM non-invasive diagnosis and shed light on DCM pathogenesis and therapeutic targets.
Clinical and translational medicine 2023
Background:Coronary artery disease (CAD) can lead to left ventricular (LV) remodeling, which, in adverse cases, has been associated with heart failure and increased mortality. Here, we aimed to evaluate the predictive value of the noninvasive myocardial work index (NIMWI) for LV reverse remodeling in patients with multivessel CAD after percutaneous coronary intervention (PCI).Methods:A total of 88 consecutive patients with multivessel CAD treated with PCI were identified and categorized according to the presence of LV reverse remodeling 3 months after PCI [≥15% decrease in the LV end diastolic volume (LVEDV)]. With the LV pressure-strain loop (PSL) technique, NIMWIs, including the global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), were statistically compared between the reverse LV remodeling group and nonreverse LV remodeling group 1 week before PCI.Results:Significantly lower GWI, GCW, and GWE, and significantly higher GWW were observed in the reverse LV remodeling group compared with the nonreverse LV remodeling group (P<0.05). Left ventricular mass index (LVMI), GCW, and GWE were independently associated with early LV reverse remodeling. Receiver operating characteristic (ROC) curve analysis demonstrated that GCW was the most powerful predictor of early LV reverse remodeling in patients with CAD [area under the curve (AUC) =0.867]. The optimal cutoff GCW value predictive of early LV reverse remodeling was 1,438.5 mmHg% (sensitivity, 85%; specificity, 70%).Conclusions:GCW, among the NIMWIs, may be the major predictor of LV reverse remodeling in patients with multivessel CAD after PCI. NIMWI could potentially provide a new reference index for the quantitative evaluation of LV myocardial work.
Quantitative imaging in medicine and surgery 2022
BACKGROUND:Cardiac damage is the leading cause of death in uremic patients. This study aimed to evaluate the application of non-invasive myocardial work index (NIMWI) by echocardiography in assessing the left ventricular (LV) systolic function in uremic patients.METHODS:Twenty-six uremic patients and 27 age- and sex-matched healthy volunteers were enrolled in the study. Except for the conventional echocardiographic parameters, the LV myocardial work (MW) parameters including GWI (myocardial global work index), GCW (global constructive work), GWW (global wasted work), and GWE (global work efficiency) were calculated in study participants. Differences in MW parameters between the uremic and normal groups were compared by independent-sample t-test. Receiver operating characteristic (ROC) curves were constructed for MW parameters to detect abnormal LV systolic function in uremic patients.RESULTS:Compared with the normal group, GWW was significantly increased and GWE decreased in the uremic group (P < 0.05). Area under the curve (AUC) for GWE by the ROC analysis was 0.966. The best threshold, sensitivity and specificity values of GWE to detect abnormality of LV systolic function in uremic patients were 92.5%, 0.89 and 0.96, respectively.CONCLUSIONS:NIMWI may be applied to assess the global MW of uremic patients. The presence of reduced GWE can help identify impaired left ventricular myocardial function in uremic patients with preserved LV ejection fraction with a high sensitivity and specificity.
Biomedical engineering online 2022
Background:The capacity to distinguish hypertrophic cardiomyopathy (HCM) from hypertensive left ventricular hypertrophy (H-LVH) based on morphological features obtained by conventional echocardiography is limited. We investigated the global myocardial work of the left ventricle in two types of hypertrophies using the non-invasive myocardial work index (NMWI).Methods:Conventional echocardiography was performed on 107 subjects with preserved left ventricular ejection fraction (LVEF ≥ 50%), who comprised patients with HCM (n = 40), H-LVH (n = 35), and healthy people with normal blood pressure and left ventricular structure (n = 32). Except for the conventional echocardiographic parameters, the left ventricular myocardial work parameters based on pressure-strain loops, including global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), were evaluated in three groups. Multivariate discriminant analysis and receiver operating characteristic (ROC) curve were used to evaluate the incremental value of NMWI for distinguishing HCM from H-LVH.Results:Compared to the control group, GWI and GCW were significantly lower in HCM patients (P < 0.05), whereas GWI was significantly higher in H-LVH patients. GWW was higher and GWE was significantly decreased in both HCM and H-LVH patients than in the control group (P < 0.05). Multivariate discriminant analysis and ROC curve revealed that the inter-ventricular septum thickness (IVST)/left ventricular posterior wall thickness (LVPWT) and GCW were each able to distinguish HCM from H-LVH. The combination of IVST/LVPWT and GCW discriminated HCM and H-LVH with a higher predictive accuracy of 94.7%.Conclusion:NMWI may provide additional information in evaluating the myocardial function in patients with HCM and H-LVH. Myocardial work combined with conventional echocardiography could improve the clinical diagnostic accuracy of distinguishing HCM and H-LVH.
Frontiers in cardiovascular medicine 2022
BACKGROUND:Accurate evaluation of left ventricular (LV) systolic function is the premise for diagnosing and treating chronic heart failure. This study aimed to explore the incremental value of echocardiographic myocardial work in evaluating the LV systolic dysfunction in patients with chronic heart failure.METHODS:A total of 206 participants were enrolled, including 155 patients with chronic heart failure and 51 healthy controls (HC). The chronic heart failure patients were divided into three groups according to LV ejection fraction (LVEF): Heart failure with preserved ejection fraction (HFpEF group, 54 cases, LVEF ≥50%), heart failure with mid-range ejection fraction (HFmrEF group, 50 cases, 40%≤ LVEF <50%), and heart failure with reduced ejection fraction (HFrEF group, 51 cases, LVEF <40%). Except for the conventional echocardiographic parameters, the left ventricular myocardial work parameters, including the global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), were calculated in the study participants. One-way analysis of variance test followed by Fisher's least significant difference (LSD) t-test were used to obtain parameters with significant differences, which were then fed into a machine learning model established for subsequent multi-classification of the four groups. The selected myocardial work parameters with high importance rankings resulting from the machine learning model were further compared with the traditional LVEF in the multi-classification of the four groups.RESULTS:All conventional echocardiographic parameters were significantly different between the HFmrEF and HFrEF groups, but only E/e', left atrium showed notable differences between the HFpEF and HC groups (P<0.05). All myocardial work parameters were markedly different between the four groups (P<0.05). LVEF and GWI were more important than the other parameters according to the multi-classification machine learning model. The multi-classification diagnostic performances of LVEF, GWI, and LVEF + GWI were 82%, 88%, and 98%, respectively, which confirmed that GWI + LVEF could complementarily improve the diagnosis accuracy in classifying the four groups, with a performance increase of approximately 10% than each individually.CONCLUSIONS:GWI can play a complementary role to LVEF in the early diagnosis of HFpEF patients from the HC group and improve the clinical evaluation accuracy in chronic heart failure patients. Echocardiographic myocardial work should be utilized along with conventional LVEF to evaluate the systolic function of chronic heart failure patients in clinical practice.
Quantitative imaging in medicine and surgery 2022
Objectives: To analyze the association between global myocardial work indices evaluated by non-invasive left ventricular (LV) pressure-strain loop (PSL) and LV myocardial fibrosis in patients with dilated cardiomyopathy (DCM). Methods: A total of 57 patients with DCM were included in this prospective study. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE) and global longitudinal strain (GLS) were measured using LVPSL. LV volumes and LV ejection fraction (LVEF) were evaluated using cardiac magnetic resonance imaging (CMRI), LV myocardial fibrosis was estimated at CMRI by qualitative assessment of late gadolinium enhancement (LGE). According to the CMRI, the studied population was divided into two groups, namely: patients without LGE (LGE-) and patients with LGE (LGE+). Results: The LGE+ group presented with increased age, LV end systolic volume (LVESV) index and reduced GWI, GCW, GWE, GLS, CMRI-derived LVEF (LVEFCMRI), the differences between the two groups were statistically significant (P < 0.05). After correcting for age and LVESV index, LVEFCMRI, GLS, GWI, GCW, and GWE retained independent associations with LV myocardial fibrosis. According to receiver operating characteristics (ROC) analysis, LVEFCMRI, and GCW showed larger AUC and higher accuracy, sensitivity, and specificity than GLS, the accuracy of predicting LV myocardial fibrosis ranged from high to low as: LVEFCMRI, GCW, GWE, GWI, and GLS. Conclusions: LVEFCMRI, GWI, GCW, GWE, and GLS remained significant predictors of LV myocardial fibrosis. LVEFCMRI, and GCW appeared to better predict LV myocardial fibrosis compared with GLS.
Frontiers in cardiovascular medicine 2021
