Association between clinical phenotypes of hypertrophic cardiomyopathy and Ca2+ gene variation gene variation / 中华心血管病杂志

Objective: To observe the association between clinical phenotypes of hypertrophic cardiomyopathy (HCM) patients and a rare calcium channel and regulatory gene variation (Ca2+ gene variation) and to compare clinical phenotypes of HCM patients with Ca2+ gene variation, a single sarcomere gene variation and without gene variation and to explore the influence of rare Ca2+ gene variation on the clinical phenotypes of HCM. Methods: Eight hundred forty-two non-related adult HCM patients diagnosed for the first time in Xijing Hospital from 2013 to 2019 were enrolled in this study. All patients underwent exon analyses of 96 hereditary cardiac disease-related genes. Patients with diabetes mellitus, coronary artery disease, post alcohol septal ablation or septal myectomy, and patients who carried sarcomere gene variation of uncertain significance or carried>1 sarcomere gene variation or carried>1 Ca2+ gene variation, with HCM pseudophenotype or carrier of ion channel gene variations other than Ca2+ based on the genetic test results were excluded. Patients were divided into gene negative group (no sarcomere or Ca2+ gene variants), sarcomere gene variation group (only 1 sarcomere gene variant) and Ca2+ gene variant group (only 1 Ca2+ gene variant). Baseline data, echocardiography and electrocardiogram data were collected for analysis. Results: A total of 346 patients were enrolled, including 170 patients without gene variation (gene negative group), 154 patients with a single sarcomere gene variation (sarcomere gene variation group) and 22 patients with a single rare Ca2+ gene variation (Ca2+ gene variation group). Compared with gene negative group, patients in Ca2+ gene variation group had higher blood pressure and higher percentage of family history of HCM and sudden cardiac death (P<0.05); echocardiographic results showed that patients in Ca2+ gene variation group had thicker ventricular septum ((23.5±5.8) mm vs. (22.3±5.7) mm, P<0.05); electrocardiographic results showed that patients in Ca2+ gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (400.6±47.2) ms, P<0.05) and higher RV5+SV1 ((4.51±2.26) mv vs. (3.50±1.65) mv, P<0.05). Compared with sarcomere gene variation group, patients in Ca2+ gene variation group had later onset age and higher blood pressure (P<0.05); echocardiographic results showed that there was no significant difference in ventricular septal thickness between two groups; patients in Ca2+ gene variation group had lower percentage of left ventricular outflow tract pressure gradient>30 mmHg (1 mmHg=0.133 kPa, 22.8% vs. 48.1%, P<0.05) and the lower early diastolic peak velocity of the mitral valve inflow/early diastolic peak velocity of the mitral valve annulus (E/e') ratio ((13.0±2.5) vs. (15.9±4.2), P<0.05); patients in Ca2+ gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (399.0±43.0) ms, P<0.05) and lower percentage of ST segment depression (9.1% vs. 40.3%, P<0.05). Conclusion: Compared with gene negative group, the clinical phenotype of HCM is more severe in patients with rare Ca2+ gene variation; compared with patients with sarcomere gene variation, the clinical phenotype of HCM is milder in patients with rare Ca2+ gene variation.

Myocardial biopsy of Liwen procedure: representability and etiological diagnostic value of cardiac samples obtained by a novel technique in patients with hypertrophic cardiomyopathy / 中华心血管病杂志

Objective: To investigate the representability and etiological diagnostic value of myocardium samples obtained from patients with hypertrophic cardiomyopathy (HCM) by transthoracic echocardiography-guided percutaneous intramyocardial septal biopsy (myocardial biopsy of Liwen procedure). Methods: This study was a retrospective case-series analysis. Patients with HCM, who underwent myocardial biopsy of Liwen procedure and radiofrequency ablation in Xijing Hospital, Air Force Military Medical University from July to December 2019, were included. Demographic data (age, sex), echocardiographic data and complications were collected through electronic medical record system. The histological and echocardiographic features, pathological characteristics of the biopsied myocardium of the patients were analyzed. Results: A total of 21 patients (aged (51.2±14.5) years and 13 males (61.9%)) were enrolled. The thickness of ventricular septum was (23.3±4.5)mm and the left ventricular outflow tract gradient was (78.8±42.6)mmHg (1 mmHg=0.133 kPa). Eight patients (38.1%) were complicated with hypertension, 1 patient (4.8%) had diabetes, and 2 patients (9.5%) had atrial fibrillation. Hematoxylin-eosin staining of myocardial samples of HCM patients before radiofrequency ablation evidenced myocytes hypertrophy, myocytes disarray, nuclear hyperchromatism, hypertrophy, atypia, coronary microvessel abnormalities, adipocyte infiltration, inflammatory cell infiltration, cytoplasmic vacuoles, lipofuscin deposition. Interstitial fibrosis and replacement fibrosis were detected in Masson stained biopsy samples. Hematoxylin-eosin staining of myocardial samples of HCM patients after radiofrequency ablation showed significantly reduced myocytes, cracked nuclear in myocytes, coagulative necrosis, border disappearance and nuclear fragmentation. Quantitative analysis of myocardial specimens of HCM patients before radiofrequency ablation showed that there were 9 cases (42.9%) with mild myocardial hypertrophy and 12 cases (57.1%) with severe myocardial hypertrophy. Mild, moderate and severe fibrosis were 5 (23.8%), 9 (42.9%) and 7 (33.3%), respectively. Six cases (28.6%) had myocytes disarray. There were 11 cases (52.4%) of coronary microvessel abnormalities, 4 cases (19.0%) of adipocyte infiltration, 2 cases (9.5%) of inflammatory cell infiltration,6 cases (28.5%) of cytoplasmic vacuole, 16 cases (76.2%) of lipofuscin deposition. The diameter of cardiac myocytes was (25.2±2.8)μm, and the percentage of collagen fiber area was 5.2%(3.0%, 14.6%). One patient had severe replacement fibrosis in the myocardium, with a fibrotic area of 67.0%. The rest of the patients had interstitial fibrosis. The myocardial specimens of 13 patients were examined by transmission electron microscopy. All showed increased myofibrils, and 9 cases had disorder of myofibrils. All patients had irregular shape of myocardial nucleus, partial depression, mild mitochondrial swelling, fracture and reduction of mitochondrial crest, and local aggregation of myofibrillary interfascicles. One patient had hypertrophy of cardiomyocytes, but the arrangement of muscle fibers was roughly normal. There were vacuoles in the cytoplasm, and Periodic acid-Schiff staining was positive. Transmission electron microscopy showed large range of glycogen deposition in the cytoplasm, with occasional double membrane surround, which was highly indicative of glycogen storage disease. No deposition of glycolipid substance in lysozyme was observed under transmission electron microscope in all myocardial specimens, which could basically eliminate Fabry disease. No apple green substance was found under polarized light after Congo red staining, which could basically exclude cardiac amyloidosis. Conclusion: Myocardium biopsied samples obtained by Liwen procedure of HCM patients are representative and helpful for the etiological diagnosis of HCM.

The role of three-dimensional speckle tracking imaging derived parameters on predicting outcome of hypertrophic cardiomyopathy patients with MYH7 mutations / 中华心血管病杂志

Objective: To evaluate the cardiac functional changes in hypertrophic cardiomyopathy(HCM) patients with β-myosin heavy chain gene (MYH7) mutations by three-dimensional (3D) speckle tracking imaging(3D-STI) and conventional echocardiography modalities, and then to explore the potential predictors of adverse cardiovascular events in these patients. Methods: A consecutive series of 192 HCM patients admitted in our center from October 2014 to October 2016 were genetically screened to identify MYH7 mutations in this retrospective study. A total of 43 HCM patients with MYH7 mutations were enrolled. The patients were divided into events group(n=13) and no event group(n=30) according to the presence or absence of adverse cardiovascular events(primary and secondary endpoints). All patients were followed up to January 2019 after comprehensive evaluation of 3D-STI, two-dimensional and Doppler echocardiography. The adverse cardiovascular events were recorded. Results: The median follow up time was 1 012 (812, 1 330) days. During follow-up, 13 patients (30.2%) reached endpoints: 6 cases of the primary endpoints(2 cases of sudden cardiac death(SCD), 3 cases of survival after defibrillation, and 1 case of appropriate implantable cardioverter-defibrillator(ICD) discharge); 7 cases of the second endpoints(5 cases of heart failure hospitalization, 1 case of syncope and cardioversion due to supraventricular tachycardia, and 1 case of end-stage HCM). Patients with adverse cardiovascular events had higher prevalence of syncope and risk of SCD, enlarged left atrial volume index(LAVI) and reduced 3D left ventricular global longitudinal train (3D-GLS), as compared to those without adverse events(all P<0.05). The multivariate Cox regression analysis showed that reduced 3D-GLS(HR=0.814, 95%CI 0.663-0.999, P=0.049) was an independent predictor for adverse cardiovascular events. The cutoff value of 3D-GLS≤13.67% was linked with significantly increased risk of adverse cardiovascular events in this patient cohort(AUC=0.753, 95%CI 0.558-0.948, sensitivity 86%, specificity 69%, P<0.05). The Kaplan-Meier analysis indicated that the patients with the 3D-GLS≤ 13.67% faced higher risk of death than those with 3D-GLS>13.67%. Conclusion: 3D-GLS is useful on predicting adverse cardiovascular events in HCM patients with MYH7 mutations.

Blood Routine Analysis of Patients with Herpes Zoster at Early Stage,Acute Cholecystitis and Acute Myocardial Infarction / 现代检验医学杂志

Objective To evaluate the diagnostic value of these alternant indexes by compare the results of routine blood test of early herpes zoster(HZ),acute cholecystitis and acute myocardial infarction patients.Methods According to some inclu-sion and exclusion criteria,78 HZ patients,59 acute cholecystitis and 51 acute myocardial infarction patients from October 2013 to March 2017 were included.The receiver operator characteristics(ROC)were used to evaluate the diagnostic value of the blood corpuscle indexes.Results White blood cell count(WBC),blood platelet count(PLT)and neutrophilic granulo-cyte percentage(NE%)of HZ patients were lower than the acute cholecystitis and acute myocardial infarction patients(P<0.001).Lymphocyte percentage(LYM%)and monocyte percentage(MO%)were higher than the others'.The NE% index had a certain diagnostic value(AUC=0.848,95%CI:0.792~0.905).There was a highest specificity in LYM% index(spe-cificity=0.963).Conclusion There were some clinical significance of routine blood cell count results on the early HZ diag-nosis,which can reduce the missed diagnosis and misdiagnosis rate of an early diagnosis herpes zoster.

Relative risk factors of patients with coronary heart disease combined with renal artery stenosis / 解放军医学杂志

Objective To investigate the risk factors of atherosclerotic renal artery stenosis (ARAS) in patients with coronary heart disease.Method Six hundred and seventy-seven patients with suspected or certainly diagnosed as coronary heart disease consecutively underwent selective coronary angiography and non-selective renal artery angiography during May to Sep.2016 in the Department of Cardiology of General Hospital of Shenyang Military Region.According to the degree of renal artery stenosis,the subjects were divided into renal artery normal group,renal artery slight stenosis group (renal artery stenosis ＜50％) and renal artery obvious stenosis group (renal artery stenosis ＞50％).Both univariate and multivariate logistic regression analysis were used to study the independent risk predictors of ARAS.Results By analysis of clinical data,it was found that age,systolic blood pressure,pulse pressure and creatinine level were higher in patients with different degrees of renal artery stenosis than in renal artery normal group (P＜0.05).There were significant differences in different degrees of renal artery stenosis groups in female,hypertension,left main coronary artery (P＜0.05).The proportion of coronary double vessel lesions was higher in renal artery slight stenosis group than in renal artery normal group (P＜0.05).Age,pulse pressure and creatinine level were significantly higher in renal artery obvious stenosis group than in the other two groups (P＜0.05).Peripheral vascular disease,left main coronary artery disease,single coronary artery and three vessel disease were significantly higher than that in other two groups (P＜0.05).The incidence of renal artery obvious stenosis was 18.9％ in patients with renal artery obvious stenosis,and was 16.7％ in renal arteries slight stenosis group.By univariate and multivariate Logistic regression analysis,age,female,peripheral vascular disease,and multivessel coronary artery disease were independent risk factors for ARAS.Conclusion Renal artery angiography should be routinely performed for patients with coronary artery disease undergoing coronary angiography to identify ARAS,especially for elderly and female patients associated with peripheral vascular disease.

Analysis and follow-up study on 8 children with combined congenital heart disease treated with simultaneous trans-catheter therapy / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Interventional treatment for childhood combined congenital heart disease (CHD) has developed very quickly and more new types of occluders have emerged in recent years. The aim of this study is to investigate the efficiency and safety of interventional treatment for combined CHD in children.</p><p><b>METHODS</b>Eight children with combined CHD (4 boys and 4 girls), aged 6.1+/-2.9 years, underwent simultaneous transcatheter therapy. Of the 8 children with CHD, 1 case had atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA), 1 case had ASD, PDA and pulmonary stenosis (PS), 1 case had ASD and PDA, 1 case had patent foramen ovale (PFO) and PS, and 4 cases had ASD and PS. The methods of transcatheter intervention for these patients were as follows: in patients with ASD,VSD and PDA, the occlusion of VSD was performed first, followed by PDA and ASD occlusions; in patients with ASD, PDA and PS, the occlusion of percutaneous balloon pulmonary valvuloplasty (PBPV) was performed first, followed by PDA and ASD occlusions; in patients with PFO and PS, the occlusion of PBPV was performed first, and PFO occlusion followed; in patients with ASD and PS, the occlusion of PBPV was performed first, and ASD occlusion followed.</p><p><b>RESULTS</b>The intervention operation was successfully performed in all of the 8 patients. No serious adverse events occurred during the operation. No residual shunt was found and all the occlusion devices were in the suitable sites shown by transthoracic echocardiography (TTE) and X-ray right after the operation. In the 6 patients with PS, the systolic pressure across the pulmonary valve decreased from 75.3+/-15.6 mmHg (before operation) to 14.0+/-5.6 mmHg after operation (P<0.05).A 3.4+/-1.2 years follow-up demonstrated that no residual shunt occurred and gradients across valve or coarctation sites were within the limit of satisfactory results. No complications were observed during the follow-up.</p><p><b>CONCLUSIONS</b>Transcatheter interventional therapy for childhood combined CHD can obtain satisfactory results by proper procedures.</p>

High-performance liquid chromatographic determination of urinary trans, trans-muconic acid excreted by workers occupationally exposed to benzene / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the relationship between trans, trans-muconic acid (ttMA) as benzene metabolite of occupational workers and benzene concentration in air.</p><p><b>METHODS</b>A rapid and sensitive high-performance liquid chromatography was developed to determine the level of urinary ttMA. ttMA was extrated from urinary samples in liquid-liquid phase a ODS (2) (5u) column (phi 4.6 mm x 150 mm) and detected at wavelength 264 nm in a UV detector using vanillic acid as an internal standard. The mobile phase was acetaticacid/tetrahydrofuran/methanol/water (v/v, 1:2:10:87). The method was validated with 56 urine samples collected from occupationally benzene-exposed individuals.</p><p><b>RESULTS</b>A correlation coefficient (r = 0.9963) was found for ttMA ranging 0.10-10.00 microg/mL. The limit of detection was 0.10 microg/mL. The recovery and reproducibility were generally over 90%. There was a positive correlation between ttMA and benzene level in air. The equation was Y = 0.859 + 0.108C (before work, r = 0.6200) or Y = 1.980 + 0.179C (after work, r = 0.7930).</p><p><b>CONCLUSION</b>This method can be used to determine and control the level of urinary ttMA in those who are occupationally exposed to benzene.</p>