Ultrasonic Cardiography Research Articles

The incidence and interrelationship of hemivertebra and concomitant cardiac abnormalities in congenital scoliosis

BackgroundCongenital scoliosis(CS) is associated with multiple organs defect, and cardiac abnormalities have been reported commonly associated with CS. Hemivertebra is caused by the failure of vertebral formation, which is a major constitute of CS. Till now, few studies focus on the incidence and interrelationship of hemivertebra and concomitant cardiac abnormalities in congenital scoliosis. We aimed to analyze the cardiac defect in CS patients with or without hemivertebra, and further explore the incidence of cardiac defect between different types of hemivertebra.MethodsThe ultrasonic cardiography (UCG) results of surgically treated congenital scoliosis (CS) patients between 2015 and 2018 were retrospectively analyzed. Patients were divided into hemivertebra group and non-hemivertebra group according to preoperative CT. Patients with hemivertebra was further divided into sub-group by single/multiple or fully/partially/mixed segmented hemivertebra. Demographic information, radiographic data and cardiac abnormalities were statistically compared between groups.ResultsA total of 329 patients were analyzed, including 216 patients with hemivertebra and 113 patients without hemivertebra. UCG results were abnormal in 89 cases (27.1%), including 41 males(12.5%) and 48 females(14.6%). Hemivertebra group had comparable incidence of cardiac abnormalities with non-hemivertebra group (p = 0.517). No significant difference in the incidence of UCG abnormalities between single and multiple hemivertebra group (P = 0.246). Binary logistic regression analysis showed that female sex with multiple hemivertebra was a risk factor for abnormal UCG (P = 0.009, OR = 3.449). Cardiac abnormalities was comparable among fully, partially and mixed segmented hemivertebra group(P = 0.264). In abnormal UCG, 33 patients with hemivertebra had non-valvular abnormalities, and 48.5% (16/33) were septal defects. 28 patients had valvular abnormalities, most of them were mitral valve abnormalities, especially mitral valve redundancy, prolapse and insufficiency(82.1%, 23/28). No significant difference between the incidence of non-valvular and valvular abnormalities in patients with hemivertebra (P = 0.581).ConclusionsThe incidence of abnormal UCG results was approximately 28.2% in CS patients with hemivertebra. Female patients with multiple hemivertebra had a higher risk of UCG abnormalities. Mitral valve abnormalities were the most common abnormality of UCG found in CS patients with hemivertebra.Trial registrationretrospectively registered.

Five-Year Outcomes After Fractional Flow Reserve-Guided Deferral of Revascularization in Infarct-Related Artery Lesions.

Little evidence is available about the long-term safety of fractional flow reserve (FFR)-guided deferral of revascularization in infarct-related artery (IRA) lesions, especially when measuring FFR in the late setting after myocardial infarction (MI). This study aimed to assess the long-term outcomes after deferral of revascularization in IRA lesions based on FFR assessed in the late phase of post-MI. From the J-CONFIRM registry (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry), data on 1447 lesions (1263 patients) were divided into 2 groups: the IRA and non-IRA groups. The primary study end point was the cumulative 5-year incidence of target vessel failure (TVF), such as cardiac death, target vessel-related MI, and clinically driven target vessel revascularization. Of the 1447 lesions, 138 (9.5%) were classified into the IRA group. The median duration of FFR measurement was 716 days after MI. The frequency of visual-functional mismatches (ie, FFR >0.80 and percent diameter stenosis ≥50% or FFR ≤0.80 and percent diameter stenosis <50%) was comparable between the IRA and non-IRA groups (31.9% vs 36.3%). The cumulative 5-year incidence of TVF did not differ between the groups (9.2% vs 11.8%; inverse probability-weighted hazard ratio, 1.18, 95% confidence intervals, 0.48-2.91, P = .71). Similar results were observed irrespective of regional wall motion assessed by ultrasonic cardiography and acute MI type. The 5-year TVF rate did not differ between the IRA and non-IRA lesions when deferring revascularization guided by FFR in the late setting of post-MI.

Glycolysis Inhibition Alleviates Cardiac Fibrosis After Myocardial Infarction by Suppressing Cardiac Fibroblast Activation.

Objective: To explore the role of glycolysis in cardiac fibroblast (CF) activation and cardiac fibrosis after myocardial infarction (MI).Method: In vivo: 2-Deoxy-D-glucose (2-DG), a glycolysis inhibitor, was injected into the abdominal cavity of the MI or sham mice every day. On the 28th day, cardiac function was measured by ultrasonic cardiography, and the hearts were harvested. Masson staining and immunofluorescence (IF) were used to evaluate the fibrosis area, and western blot was used to identify the glycolytic level. In vitro, we isolated the CF from the sham, MI and MI with 2-DG treatment mice, and we also activated normal CF with transforming growth factor-β1 (TGF-β1) and block glycolysis with 2-DG. We then detected the glycolytic proteins, fibrotic proteins, and the concentrations of lactate and glucose in the culture medium. At last, we further detected the fibrotic and glycolytic markers in human fibrotic and non-fibrotic heart tissues with masson staining, IF and western blot.Result: More collagen and glycolytic protein expressions were observed in the MI mice hearts. The mortality increased when mice were treated with 2-DG (100 mg/kg/d) after the MI surgery (Log-rank test, P < 0.05). When the dosage of 2-DG declined to 50 mg/kg/d, and the treatment was started on the 4th day after MI, no statistical difference of mortality between the two groups was observed (Log-rank test, P = 0.98). The collagen volume fraction was smaller and the fluorescence signal of α-smooth muscle actin (α-SMA) was weaker in mice treated with 2-DG than PBS. In vitro, 2-DG could significantly inhibit the increased expression of both the glycolytic and fibrotic proteins in the activated CF.Conclusion: Cardiac fibrosis is along with the enhancement of CF activation and glycolysis. Glycolysis inhibition can alleviate cardiac fibroblast activation and cardiac fibrosis after myocardial infarction.

Hypertension treatment status and ultrasonic cardiography findings in temporary housing residents after the Kumamoto earthquake: a cross-sectional study

Background: We aimed to investigate and report the relationship between hypertension treatment status and cardiac functions among temporary housing residents after the Kumamoto earthquake. Material and methods: Ultrasonic cardiography examinations were conducted for 56 residents at temporary housing complexes in Minami Aso village in Kumamoto Prefecture in December 2016. The subjects were divided into the following three groups according to the incidence of hypertension and the antihypertensive treatment status: normal (without hypertension), treated, and untreated. Subsequently, their cardiac functions were compared. Results: Age and BMI were found to be positive predictors for hypertension. Moreover, age, LAVI, and LVMI tended to be higher in the untreated group than in the treated group. Moderate or severe mitral regurgitation was significantly more common in the untreated group than in the treated group. Conclusions: Controlling blood pressure may help to prevent new cardiac diseases (e.g., valve regurgitation) among survivors after a major disaster. In addition, for survivors who are severely affected by psychological stress, improving the mental stress support system may be an effective measure to reduce health problems.

Effects and Mechanism of Noninvasive Positive-Pressure Ventilation in a Rat Model of Heart Failure Due to Myocardial Infarction.

BackgroundImpaired heart function induced by myocardial infarction is a leading cause of chronic heart failure (HF). This study aimed to investigate the effects and mechanism of noninvasive positive-pressure ventilation (NIPPV) in a rat model of HF due to myocardial infarction.Material/MethodsTo explore the therapeutic effect and mechanism of NIPPV on acute myocardial infarction-induced HF, we established a rat model of HF by ligating the anterior descending branch of the left coronary artery and confirmed by ultrasonic cardiography and brain natriuretic peptide 45 detection.ResultsThe levels of heat-shock protein (HSP)-70 increased and matrix metalloproteinase (MMP)-2, MMP-9, and tumor necrosis factor (TNF)-α decreased in the group that received NIPPV treatment compared with the control group. In addition, the histopathologic results showed less severe inflammatory infiltration and a smaller area of myocardial fibrosis in the NIPPV treatment group.ConclusionsIn a rat model of HF due to myocardial infarction, NIPPV resulted in increased levels of HSP70 and reduced expression of MMP2, MMP9, and TNF-α and reduced myocardial neutrophil infiltration and fibrosis. Taken together, we showed that NIPPV is an effective treatment for HF induced by myocardial infarction by inhibiting the release of inflammatory factors and preventing microvascular embolism.

Dasatinib-related pulmonary adverse events in patients with chronic myeloid leukemia

目的探索慢性髓性白血病（CML）患者接受达沙替尼治疗中肺部不良反应的发生率、影响因素及治疗转归。方法回顾性分析2008年4月至2020年1月在北京大学人民医院接受达沙替尼治疗的CML患者胸腔积液（PE）和肺动脉高压（PAH）的发生情况。结果共纳入280例患者，中位达沙替尼治疗时间26（1～142）个月，发现PE 90例（32.1％），其中1级40例（44.4％），2级44例（48.9％），3级6例（6.7％）。PE发生率随服药时间延长逐渐升高，多因素分析结果显示，年龄增加（每增加10岁，HR＝1.6，P<0.001）、服用达沙替尼时处于进展期（HR＝2.2，P＝0.008）和有心血管疾病合并症（HR＝1.9，P＝0.018）与PE发生显著相关。服用达沙替尼时处于进展期（HR＝3.4，P＝0.001）、确诊至开始服用酪氨酸激酶抑制剂时间≤6个月（HR＝2.2，P＝0.015）、发现PE时剂量<100 mg/d（HR＝3.1，P＝0.001）者PE程度更重。经减停达沙替尼、利尿、胸腔穿刺或置管等干预，半数患者PE减少或消失。减量服用达沙替尼的患者中，绝大多数可维持原治疗反应。在有咳嗽、胸闷或气促等症状的60例患者中，49例接受超声心动图（UCG）检查，8例（16.3％）发现PAH高度可能性，约占所有患者中的3.5％，其中6例（75.0％）合并PE，PAH为可逆性。原研与国产达沙替尼的PE和PAH发生率差异无统计学意义（P>0.05）。结论在服用达沙替尼的CML患者中，PE是常见的不良反应，PAH较少见，应注意识别高危人群、密切监测和及时干预。

Safety and efficacy of INTRABEAM intraoperative radiotherapy for invasive thymoma.

Intraoperative radiotherapy (IORT) has been used to treat different residual solid tumors after tumor removal and has shown many advantages over other treatment methods. However, the use of IORT for invasive thymoma has not been reported. Therefore, in this study, we tried to determine the safety and efficacy of INTRABEAM IORT for the treatment of invasive thymoma.Among the patients admitted to our hospital from September to December 2016 who were diagnosed with invasive thymoma, 14 were selected as study subjects. With medical histories taken beforehand, 8 of these patients were diagnosed with Masaoka stage IIA and 6 with Masaoka stage IIB; furthermore, 5 of the patients were diagnosed with myasthenia gravis (MG). INTRABEAM radiation (8–10 Gy, low energy) was delivered to the postoperative tumor bed of each patient during surgery. The intra- and postoperative complications were observed and evaluated, and the improvement in symptoms was assessed. An additional 23 patients with stage II thymoma undergoing radical surgery from April to August 2016 were chosen as the control group.One month after the operation, only 1 patient in the IORT group had cough, increased levels of leucocytes and neutrophils, and pulmonary inflammation on chest computed tomography. Reactive inflammation and pleural effusion in the 2 groups were similar (P > .05). There was no significant difference between the 2 groups in the improvement of myasthenia gravis (P > .05). Postoperative chest computed tomography and routine blood examination at 3 and 12 months showed that all the patients recovered, with normal hemogram levels and no pulmonary fibrosis around the radiation field. In addition, ultrasonic cardiography and electrocardiography demonstrated no significant difference before or after surgery within the IORT group. At the end of the follow-up, all the patients were alive, no relapse or remote metastasis was observed in the IORT group, and 2 inpatients in the control group had experienced relapse at 24 and 26 months. There was a significant difference in disease-free survival between the 2 groups (P = .00).It is safe to administer low-energy INTRABEAM IORT at a dose of approximately 10 Gy in patients with stage II invasive thymoma. INTRABEAM IORT does not significantly increase operation- or radiation-related complications and has no significant effect on vital organs such as the lungs and heart. Its long-term efficacy is worth expecting.

Qingyi decoction protects against myocardial injuries induced by severe acute pancreatitis

BACKGROUNDWe studied the protective effects of Qingyi decoction (QYD) (a Traditional Chinese Medicine) against severe acute pancreatitis (SAP)-induced myocardial infarction (MI).AIMTo study the function and mechanism of QYD in the treatment of myocardial injuries induced by SAP.METHODSUltrasonic cardiography, hematoxylin and eosin staining, immunohistochemistry, qRT-PCR, western blot, enzyme-linked immunosorbent assays, and apoptosis staining techniques were used to determine the effects of QYD following SAP-induced MI in Sprague-Dawley rats.RESULTSOur SAP model showed severe myocardial histological abnormalities and marked differences in the symptoms, mortality rate, and ultrasonic cardiography outputs among the different groups compared to the control. The expression of serum cytokines [interleukin (IL)-1ß, IL-6, IL-8, IL-12, amyloid β, and tumor necrosis factor-α] were significantly higher in the SAP versus QYD treated group (P < 0.05 for all). STIM1 and Orai1 expression in myocardial tissue extracts were significantly decreased post QYD gavage (P < 0.001). There was no significant histological difference between the 2-aminoethyl diphenylborinate inhibitor and QYD groups. The SAP group had a significantly higher apoptosis index score compared to the QYD group (P < 0.001).CONCLUSIONQYD conferred cardio-protection against SAP-induced MI by regulating myocardial-associated protein expression (STIM1 and Orai1).

Deficiency of Interleukin-36 Receptor Protected Cardiomyocytes from Ischemia-Reperfusion Injury in Cardiopulmonary Bypass.

BackgroundInterleukin-36 has been demonstrated to be involved in inflammatory responses. Inflammatory responses due to ischemia-reperfusion injury following cardiopulmonary bypass (CPB) can cause heart dysfunction or damage.Material/MethodsThe CPB models were constructed in IL-36R−/−, IL-36RN−/−, and wild-type SD rats. Ultrasonic cardiography and ELISA were used to evaluate the cardiac function and measuring myocardial biomarker levels in different groups. TUNEL assay was used to evaluate apoptosis. Western blot assays and RT-PCR were performed to measure the expression of chemokines and secondary inflammatory cytokines in the heart. Oxidative stress in tissue and cultured cells was assessed using a DCFH-DA fluorescence probe and quantification of superoxide dismutase activity.ResultsImproved systolic function and decreased serum levels of myocardial damage biomarkers were found in IL-36R−/− rats compared to WT rats, while worse cardiac function and cardiomyocyte IR injury were observed in IL-36RN−/− rats compared to WT rats. TUNEL staining and Western blot analyses found that cardiomyocyte apoptosis and inflammation were significantly lower in the hearts of IL-36R−/− rats compared with that of WT rats. Oxidative stress was significantly lower in IL-36R−/− rats compared to WT rats. iNOS expression was significantly reduced, while eNOS expression was increased in the hearts of IL-36R−/− rats. Silencing of IL-36R expression in vitro activated SIRT1/FOXO1/p53 signaling in cardiomyocytes.ConclusionsIL-36R deficiency in cardiomyocytes repressed infiltration of bone marrow-derived inflammatory cells and oxidative stress dependent on SIRT1-FOXO1 signaling, thus protecting cardiomyocytes and improving cardiac function in CPB model rats.

Comparison of pancreatic and renal blood flow in a canine tachycardia-induced cardiomyopathy model.

The pancreas is believed to be vulnerable to hypoperfusion. In dogs with acute pancreatitis, pancreatic ischemia due to heart failure can worsen the condition. However, changes in pancreatic blood flow associated with decreased cardiac function have not been previously studied in dogs. Therefore, we aimed to identify and compare changes in pancreatic versus renal blood flow as a result of cardiac dysfunction. Seven dogs were subjected to rapid ventricular pacing to create heart failure models. Noninvasive blood pressure measurement, ultrasonic cardiography, contrast-enhanced ultrasonography for pancreatic blood flow measurement, and para-aminohippuric acid clearance for renal blood flow measurement were performed before starting and at 2 and 4 weeks after starting the pacing. Left ventricular cardiac output and mean blood pressure decreased at 2 and 4 weeks after starting the pacing, and pancreatic blood flow decreased at 2 and 4 weeks after starting the pacing. However, renal blood flow did not change at 2 weeks but decreased 4 weeks after starting the pacing. Overall, this study demonstrated that reduced pancreatic blood flow due to cardiac dysfunction occurs, similar to renal blood flow. This suggests that decreased pancreatic blood flow is not unusual and may frequently occur in dogs with heart failure. The results of this study support the speculation that heart failure can exacerbate acute pancreatitis. Additionally, this study provides useful basic information for designing further studies to study this association.

Clinical Observation of Applying Intrabeam® Intraoperative Radiotherapy for the Treatment of Invasive Thymoma

Purpose: Intraoperative radiotherapy (IORT) has been used to treat various solid tumors, and demonstrated advantages. However, no IORT has been reported to treat invasive thymoma. The current study tried to determine the safety profile of applying INTRABEAM IORT to the treatment of invasive thymoma. Materials and methods: Among the patients admitted to our hospital from September to December, 2016 who was diagnosed with invasive thymoma, 14 were selected as subjects. They were inquired for medical history and divided into 8 stage IIA cases and 6 stage IIB cases according to Masaoka staging system. Of the 14 patients, 5 had myasthenia gravis (MG). INTRABEAM radiation (8–10 Gy, low energy) was delivered to the postoperative tumor bed of each patient during operation. The intra- and post-operative complications were detected and evaluated, and the improvement of symptoms assessed. Results: One month after operation, only one patient presented cough and increased hemogram levels, chest CT (computerized tomography) showed pulmonary inflammation. Postoperative chest CT at 3 and 12 months showed that all the patients returned to normal, without cough or pulmonary fibrosis surrounding the radiation field. In addition, ultrasonic cardiography and electrocardiogram (ECG) demonstrated no significant difference before and after surgery. At the end of the follow-up, all the patients were alive, no relapse or remote metastasis had been found. Conclusion: It is safe to administer INTRABEAM IORT at a dose of about 10 Gy with low energy to patients with stage II invasive thymoma. The INTRABEAM IORT does not significantly increase operation- or radiation-related complications, has no significant effect on the vital organs around the radiation field, such as lung and heart. The long-term efficacy is worth expecting.

PO-286 The research about the evaluation index on cardiac reserve of female athletes

PO-286 The research about the evaluation index on cardiac reserve of female athletes

Regulation of autophagy by tea polyphenols in diabetic cardiomyopathy

To investigate the effect of tea polyphenols on cardiac function in rats with diabetic cardiomyopathy, and the mechanism by which tea polyphenols regulate autophagy in diabetic cardiomyopathy. Sixty Sprague-Dawley (SD) rats were randomly divided into six groups: a normal control group (NC), an obesity group (OB), a diabetic cardiomyopathy group (DCM), a tea polyphenol group (TP), an obesity tea polyphenol treatment group (OB-TP), and a diabetic cardiomyopathy tea polyphenol treatment group (DCM-TP). After successful modeling, serum glucose, cholesterol, and triglyceride levels were determined; cardiac structure and function were inspected by ultrasonic cardiography; myocardial pathology was examined by staining with hematoxylin-eosin; transmission electron microscopy was used to observe the morphology and quantity of autophagosomes; and expression levels of autophagy-related proteins LC3-II, SQSTM1/p62, and Beclin-1 were determined by Western blotting. Compared to the NC group, the OB group had normal blood glucose and a high level of blood lipids; both blood glucose and lipids were increased in the DCM group; ultrasonic cardiograms showed that the fraction shortening was reduced in the DCM group. However, these were improved significantly in the DCM-TP group. Hematoxylin-eosin staining showed disordered cardiomyocytes and hypertrophy in the DCM group; however, no differences were found among the remaining groups. Transmission electron microscopy revealed that the numbers of autophagosomes in the DCM and OB-TP groups were obviously increased compared to the NC and OB groups; the number of autophagosomes in the DCM-TP group was reduced. Western blotting showed that the expression of LC3-II/I and Beclin-1 increased obviously, whereas the expression of SQSTM1/p62 was decreased in the DCM and OB-TP groups (P<0.05). Tea polyphenols had an effect on diabetic cardiomyopathy in rat cardiac function and may alter the levels of autophagy to improve glucose and lipid metabolism in diabetes.

Abstract P025: Left Atrial Dilatation Predicts The Incidence Of Persistent Atrial Fibrillation In Japanese General Population; The Suita Study

Objective: Atrial fibrillation (AF) is an important risk factor for cardiovascular disease (CVD). Left atrial (LA) dilatation detected by ultrasonic cardiography (UCG) has been reported to be associated with the incidence of AF in Western countries. However, the relationship between LA dilatation and the AF incidence has not been well investigated in Asian countries, with lower incidence of AF and obesity and with higher incidence of hypertension and stroke. To investigate the relationship between LA dilatation and the AF incidence in Japanese general population, we estimated the multivariate-adjusted hazard ratios (HR) of LA dilatation assessed by UCG for the incidence of AF. Methods: Participants were 1,585 individuals without AF (665 men, 920 women) who are the participants of a prospective cohort study for CVD incidence in urban Japanese general population (the Suita study). The mean±SD age of the participants were 67.8±7.0 years. Transthoracic UCG was performed from July in 2007 to June in 2013, and LA dimension was determined in accordance with American Society of Echocardiography recommendations by M-mode echocardiograms. After the UCG, the electrocardiograms (ECG) were repeatedly performed until March in 2016. The physicians coded the ECG using Minnesota Code (MC), and AF code is defined as 8-3-1. The HRs of LA dilatation for the incidence of AF with 95% confidence interval (CI) were estimated by Cox proportional hazard model with the adjustment for the followings at the UCG test; age, sex, systolic blood pressure, body mass index, the presence of heavy drinking (more than 2 drinks/day), non-HDL cholesterol, and the presence of the moderate or severe mitral or aortic valve abnormality detected by UCG. Results: The mean follow-up period from UCG to the last ECG was 4.6±1.8 years, and 19 AF incidences were detected. The multivariate-adjusted HR of the LA dilatation (&gt;40 mm) for the incidence of AF was 8.19 (95% CI: 2.47-27.14). And the multivariate-adjusted HR of 5 mm increment of LA dimension was 2.95 (1.65-5.29), and that of the highest quartile of LA dimension compared to the lowest was 3.37 (0.64-17.78). Among 674 participants with left atrial volume index (LAVI) data (5 AF cases), the multivariate-adjusted HR of LAVI ≥ 32 (ml/m 2 ) for AF incidence was 3.93 (95%CI: 0.34-45.86), and it showed the highest HR among the co-adjusted factors. Conclusion: LA diameter assessed by UCG is a simple and non-invasive clinical data, and could be a useful factor for the prediction of AF incidence among Japanese general population. Although the follow-up period was not enough compared to the previous studies in Western population, the present study might indicate that individuals with LA dilation detected by UCG are the important candidate for careful and continuous check-ups about CVD risk factors, ECG and UCG in Asian population.

N-terminal pro brain natriuretic peptide as a cardiac biomarker in Japanese hemodialysis patients.

This study examined the clinical significance of N-terminal pro brain natriuretic peptide level as a cardiac marker in Japanese hemodialysis patients. This was a multicenter cross-sectional study involving 1428 Japanese hemodialysis patients. Ultrasonic cardiography data at post-hemodialysis were obtained from 395 patients. We examined whether serum N-terminal pro brain natriuretic peptide levels were associated with cardiac parameters and assessed cut-off values and investigated factors associated with a reduced ratio of N-terminal pro brain natriuretic peptide levels pre- and post-hemodialysis. Multivariate logistic regression analysis showed that pre- and post-hemodialysis N-terminal pro brain natriuretic peptide levels were associated with left ventricular hypertrophy on electrocardiogram (odds ratio: 3.10; p < 0.001 at pre-hemodialysis and odds ratio: 2.70; p < 0.001 at post-hemodialysis) and left ventricular hypertrophy on ultrasonic cardiography (odds ratio: 3.06; p < 0.001 at pre-hemodialysis and odds ratio: 3.15; p < 0.001 at post-hemodialysis). Post-N-terminal pro brain natriuretic peptide levels were also significantly associated with ejection fraction on urine chorionic gonadotrophin (ultrasonic cardiography; odds ratio: 35.83; p < 0.001). Receiver operating characteristic curves for predicting the presence of left ventricular hypertrophy on electrocardiogram and ultrasonic cardiography showed similar sensitivity (57.7%, 57.3% at pre-hemodialysis and 63.9%, 48.2% at post-hemodialysis) and specificity (66.5%, 72.9% at pre-hemodialysis and 59.2%, 81.9% at post-hemodialysis). Decreased ejection fraction on ultrasonic cardiography showed better sensitivity (78.6%) and specificity (88.7%). The N-terminal pro brain natriuretic peptide reduction ratio during a hemodialysis session correlated with Kt/V, membrane area, membrane type, modality, body weight gain ratio, treatment time, and ultrafiltration rate with multiple linear regression ( R: 0.53; p < 0.001 except for ultrafiltration rate ( p = 0.003)). Both pre- and post-hemodialysis N-terminal pro brain natriuretic peptide are associated with the presence of left ventricular hypertrophy in this population. The post-hemodialysis N-terminal pro brain natriuretic peptide level is a useful marker for systolic dysfunction.

Efficacy and Safety of Zhenyuan Capsule for Coronary Heart Disease with Abnormal Glucose and Lipid Metabolism: Study Protocol for a Randomized, Double-Blind, Parallel-Controlled, Multicenter Clinical Trial.

Background Coronary heart disease (CHD) and abnormal glucose and lipid metabolism are closely associated and generally coexist. The Qi and Yin deficiency syndrome is a common disease pattern encountered in traditional Chinese medicine. We designed a protocol to determine the effectiveness and safety of Zhenyuan capsules for CHD with abnormal glucose and lipid metabolism. Methods This multicenter, randomized, double-blind, parallel-controlled trial was designed in accordance with the CONSORT. We will recruit 200 eligible male patients aged 45–75 years from three participating centers and randomly assign them to treatment and control groups (1 : 1). The primary indicators are glycosylated hemoglobin, fasting blood glucose, 2-hour postprandial blood glucose, and triglyceride levels. The secondary indicators are the Seattle Angina Questionnaire, TCM symptom indicators, ultrasonic cardiography finding, coagulation indicator, and P-selectin level. Measurements will be performed at baseline (T0), the end of the run-in period (T1), and weeks 4 (T2), 8 (T3), and 12 (T4) of the treatment period. Adverse events will be monitored during the trial. Discussion This study aims to evaluate the efficacy and safety of Zhenyuan capsules in patients with CHD and abnormal glucose and lipid metabolism. The results will provide critical evidence of the usefulness of the Chinese herbal medicine for CHD with abnormal glucose and lipid metabolism. Trial Registration This trial is registered with the Chinese Clinical Trials Registry, with identifier number ChiCTR-TRC-14004639, May 4, 2014.

Application of gated myocardial perfusion imaging in elderly patients with left-sided heart failure

Objective To investigate the clinical application of gated myocardial perfusion imaging combined with ultrasonic cardiography in elderly patients with left-sided heart failure and normal left ventricular ejection fraction(LVEF), thereby providing an important basis for the management of clinical heart failure. Methods Hospitalized patients with left-sided heart failure were divided into two groups, one with normal LVEF(n=46)and the other with reduced LVEF(n=60). Of the 106 patients, 39 were male and 67 female, aged between 60 and 85 years, with an average age of 69.8±16.8.Gated myocardial perfusion imaging was performed for patients in both groups, recording stress/rest left ventricular end-systolic volume and end-diastolic volume in duplicate, and χ2 test was conducted to detect differences in ischemic area and ventricular volume between the two groups. Results In the group with normal LVEF, gated myocardial perfusion imaging identified mild ischemia in 11 cases, moderate ischemia in 22 cases and severe ischemia in 13 cases, with the ischemic area at(15.6±6.6)%, the standard deviation at -2.3±1.1 and LVEF at(56.8±9.6)%.In the group with reduced LVEF, mild ischemia was found in 8 cases, moderate ischemia in 27 cases and severe ischemia in 15 cases, with the ischemic area at(22.0±8.6)%, the standard deviation at -3.1±2.6 and LVEF at 31.9±6.5%.Differences in ischemic area, severity of ischemia and LVEF between the groups were statistically significant(all P<0.01), as were differences in stress end-diastolic volume, rest end-diastolic volume, stress end-systolic volume and rest end-systolic volume(all P<0.01), and differences in left ventricular end-diastolic diameter, diastolic interventricular septal thickness, posterior left ventricular wall end-diastolic thickness and left ventricular apical diastolic myocardial thickness(all P<0.01). Conclusions Gated myocardial perfusion imaging is a valuable clinical tool in the diagnosis and assessment of left-sided heart failure in the elderly and may help achieve timely and standardized management for this disorder. Key words: Gated blood-pool imaging; Stroke volume; Heart failure

Prognosis Evaluation of Pulmonary Endarterectomy for Chronic Thromboembolic Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the leading causes of severe pulmonary hypertension (PH) curable by pulmonary endarterectomy (PEA) necessarily made in the reference centers. We report the case of a 30-year-old woman with a history of antiphospholipid syndrome diagnosed after a thromboembolic event responsible of her first pregnancy abortion. Two years after this event, she presented a massive and bilateral pulmonary embolism after the delivery of his second pregnancy. She was hospitalized in the intensive care unit and she received thrombolytic treatment relayed by vitamin K antagonists. One year later, she developed progressive dyspnoea (class III NYHA) and hemoptysis. Ultrasonic cardiography showed severe pulmonary hypertension (Systolic arterial pulmonary pressure at 120 mmHg) and at the right cardiac catheterization (mean arterial pulmonary pressure at 90 mmHg). Computed tomography pulmonary angiogram and ventilation-perfusion lung scan concluded on CTEPH. Blood gases showed a moderate hypoxemia (58 mmHg); conventional treatment was prescribed (oxygen, vitamine K antagonists and diuretics). The patient was referred to the reference surgical center in Paris and a pulmonary endarterectomy was done. After the surgery, the patient reports an improvement of the class of dsypnea and of the sub-maximal aerobic capacity. The systolic pulmonary pressure decreased at 50 mmHg in the ultrasonic cardiography. The patient actually has a better quality of life and rapidly resumed work.

病理解剖で明らかとなった肝内胆管癌からの腫瘍塞栓性肺微小血管障害の1例(Pulmonary tumor thrombotic microangiopathy caused by intrahepatic cholangiocarcinoma)

腫瘍塞栓性肺微小血管障害（pulmonary tumor thrombotic microangiopathy: PTTM）は，肺動脈腫瘍塞栓の特殊な型として報告された新しい疾患概念である。前医にて慢性閉塞性肺疾患に対するリハビリ目的で入院中の71歳男性が，突然の低酸素血症を伴うショックを呈し当院へ救急搬送となった。造影CT検査により肺塞栓症は否定されたが，来院6時間後，急速な酸素化障害から心停止に至りECMO（extracorporeal membranous oxygenation）を導入した。著明な肺高血圧状態にあることが判明したが，治療抵抗性であり入院8日目にECMO離脱困難のまま死亡となった。その後の病理組織診断にて肝内胆管癌由来のPTTMであることが判明した。PTTMは肺動脈内皮の増生を伴う腫瘍塞栓が特徴的な病態で，本症例のように急性増悪する肺高血圧症を認めた際に鑑別を要する病態と考えられる。 Pulmonary tumor thrombotic microangiopathy (PTTM) is a new disease concept that has been reported as a specific type of pulmonary tumor embolism. A 71–year–old man who was undergoing rehabilitation for chronic obstructive pulmonary disease in a different hospital was transported to our hospital due to sudden shock with hypoxia. Initial CT examination was negative for acute pulmonary embolism. Six hours after admission, he went into cardiac arrest following rapid progression of impaired oxygenation, and percutaneous cardiopulmonary support was introduced. Remarkable pulmonary hypertension was identified that was intractable to treatment, and it eventually led to his death 8 days after admission. Subsequent pathological diagnosis revealed the presence of PTTM derived from intrahepatic cholangiocarcinoma. PTTM is characterized by tumor emboli accompanied by endothelial proliferation in the pulmonary vasculature. It should be considered as one differential diagnosis when a patient presents with acute progressive pulmonary hypertension as in this case. 救急領域において，肺高血圧を伴う急性呼吸不全の原因検索は，治療方針の決定のために重要となる。本症例は急速進行性かつ治療抵抗性の肺高血圧を呈し原因不明のまま死に至り，その後の病理組織診断により腫瘍塞栓性肺微小血管障害（pulmonary tumor thrombotic microangiopathy: PTTM）を基盤とする病態であったことが明らかになった1例である。 71歳の男性である。60歳までの40年間の喫煙歴（20本/日）があり，高血圧で内服加療中であった。当院への入院1か月ほど前より労作時呼吸困難が出現したために前医を受診し，慢性閉塞性肺疾患（chronic obstructive pulmonary disease: COPD）と診断され入院となった。入院時の心エコー検査では，異常所見は認められなかった。入院18日目，仰臥位から側臥位への体位変換後に突然の呼吸苦とSpO2の低下を認め，ショック状態となった。血液ガス検査では，pH 7.2，PaO2 71mmHg，PaCO2 21.5mmHg，BE –15mmol/L（O2 8L/minリザーバーマスク投与下）と代謝性アシドーシスを伴う低酸素血症を認めた。輸液負荷と非侵襲的陽圧換気の導入によりショックは一時的に解除された。翌日に精査・集中治療目的に当院へ緊急搬送となった。 当院入院時の身体所見は，血圧115/69mmHg，心拍数115bpmで整，呼吸数26/分，SpO2 96%，腋窩体温37.2°C，意識清明で問診聴取は可能であった。聴診上ラ音は聴取せず，右季肋部に圧痛を認めたが反跳痛や筋性防御は認められなかった。動脈血液ガス分析上では，著しい酸素化の障害と極端な過換気を呈していた（Table 1）。血液検査では，白血球増多を伴わないCRPの軽度上昇と貧血，血小板減少を認めた。間接型優位の高ビリルビン血症が存在し，著明なトランスアミナーゼ，LDHの上昇を伴っていた。ヘモグロビン尿を認め，血清総ハプトグロビン値は測定閾値以下であった。D–ダイマーは増加していた（Table 1）。来院時の胸部X線は気腫性変化を認めるのみであった。胸部CT検査所見は前医と著変なく気管支壁の軽度肥厚と両側肺野の気腫性変化を伴っていたが，主幹肺動脈内に血栓は同定されなかった（Fig. 1a）。腹部CT検査では，肝臓に数mm径の多発性結節影，壁肥厚を伴う胆嚢腫大と周囲の限局性腹水，傍大動脈リンパ節腫脹を認めた（Fig. 1b）。心電図上は異常所見を認めなかった。 (O2 10L/min) (mask with reservoir bag) Findings of CT scan on admission. a: Contrast–enhanced CT imaging of the chest. Filling defect suggesting pulmonary thrombosis/embolism could not be detected. b: Contrast–enhanced CT imaging of the abdomen. The CT showed thickening of the gallbladder wall with surrounding fluid (circle), paraaortic lymphadenopathy (arrow), and multiple low density nodules in the liver (square). c: Ultrasonic cardiography after the resuscitation from cardiac arrest. It revealed that the right ventricle dilated obviously in association with collapse of the left ventricle. RV and LV indicate right ventricle and left ventricle, respectively. 以上より，入院当初は画像所見より急性胆嚢炎からの敗血症性ショックを考慮し，抗菌剤投与とハプトグロビン投与を行い，人工呼吸器管理を視野に入れながら精査・加療方針を立てることになった。その途上，入院約4時間後に突然不穏状態となり，モニター上SpO2の低下が急速に進行し始めた後に血圧が急激に低下し心停止となった。初期波形は心静止であり，速やかに心肺蘇生を開始したが循環虚脱が持続したためECMO（extra–corporeal membranous oxygenation）を導入し，心停止から23分後に心拍再開を得た。 心拍再開直後，再度速やかに造影CT検査を行ったが，主幹肺動脈に塞栓像は認められなかった。心エコー検査では，前医で認めていなかった左室の虚脱を伴う著明な右室の拡張像が認められ（Fig. 1c），高度な肺高血圧症を基礎病態として低酸素血症が急速に進行したために心停止に至ったものと考えられた。しかし，なぜ肺高血圧症が急速に出現したのか，その時点では原因を指摘することができなかった。Swan–Ganzカテーテルを挿入にて高度な肺高血圧状態にあることが確認され，一酸化窒素吸入やミルリノン静注療法を順次開始した（Fig. 2）。第3病日には，胸骨圧迫が原因と考えられる心嚢液貯留を認めたため，心嚢開窓術を施行した。いずれの治療効果も乏しく，平均肺動脈圧 60mmHg前後，中心静脈圧 46mmHg，CI 1.0 L/min/m2とさらに肺高血圧症の進行を認めた。ECMO下にても循環動態維持困難となり，第7病日に死亡確認となった。家族に承諾の上，病理解剖を施行した。 Clinical course after admission. Polygonal lines: systoric and diastolic arterial blood pressure, Crosses: mean pulmonary arterial pressure, Closed circles: cardiac index, NO: nitrogen monoxide, CPA: cardiopulmonary arrest, iv: intravenous injection, V–A ECMO: venous–arterial extracorporeal membrane oxygenation 病理所見上，両肺ともに出血性肺梗塞を認め，肺動脈に関しては毛細血管から径200μm前後の細動脈まで様々な径の血管内に，肺静脈については径1,000μm前後の細静脈内にまで腫瘍塞栓を多発性に認めた（Fig. 3a）。同時に，再疎通を伴う器質化フィブリン血栓を認め（Fig. 3a），血管壁は内膜の線維性肥厚を伴い（Fig. 3b），肺腫瘍塞栓性肺微小血管障害（PTTM）と診断した。肝臓のマクロ所見では，区域を越えて白色調の結節が散在していた。HE染色にて，壊死を伴い腺腔形成の乏しい異型上皮が小胞巣を形成し増生する像が主体で，一部腺腔形成を示す領域が認められた。異型上皮は非腫瘍肝索との連続性を認め，腫瘍胞巣辺縁では置換性発育を示し，腫瘍胞巣内部では既存門脈域構造が保持されていた。腫瘍細胞はCK（cytokeratin）7陽性，CK20陰性，EMA（epithelial membrane antigen）陽性，HSA（hepatocyte specific antigen）陰性であり，HE染色による形態学的特徴と合わせて，肝内胆管癌であることが判明した。大動脈周囲，肝門部，肺門部・縦隔，鎖骨窩の頸部リンパ節には細胆管癌の転移が認められ，さらには占拠された転移腫瘍細胞による骨髄抑制所見を得た。胆嚢には組織学的に明らかな炎症所見は指摘し得なかった。以上より，病理診断によって本病態は肝内胆管癌を基礎に持つPTTMであることが明らかになった。 Pathological findings of the lung and the liver. a, b: Hematoxylin and Eosin staining (a) revealed tumor emboli (black arrow) and thrombus formation (white arrow) followed by recanalization (black arrowhead) in the vessel. In addition, intimal thickening (white arrowheads) was observed by Elastica van Gieson staining (b). c: The images of immunohistochemistry to detect the expression of growth factors related to pathogenesis of PTTM. The embolized tumor cells inside the lung vessel expressed PDGF, Osteopontin, FGF–2, and VEGF, respectively (Magnification×200). 壁肥厚を伴う胆嚢腫大は右心系容量負荷に続発するうっ血によるもの，さらに頻回の輸血を要した貧血と血小板減少は骨髄転移による骨髄抑制が関与していたものであることが判明した。 その後，腫瘍から分泌され血管内膜の線維性肥厚を促進する可能性があるいくつかの因子に関して，病理組織標本を用いて免疫組織化学的に解析したところ，肺病変部の腫瘍細胞においてplatelet–derived growth factor（PDGF），osteopontin（OPN），fibroblast growth factor–2（FGF–2），vascular endothelial growth factor（VEGF）の発現を認めた（Fig. 3c）。一方，保存検体における各因子の血中濃度は正常範囲内であった。 本症例は，急速進行性かつ治療抵抗性の肺高血圧症にて死亡に至り，病理解剖でPTTMとの確定診断に至った一症例である。1987年，Goldhaberらは病理組織学的に筋性動脈以上の径をもつ肺動脈に腫瘍塞栓が存在するものを肺動脈腫瘍塞栓症と定義した 1。これに対し1990年，Herbayらは肺動脈腫瘍塞栓症の特殊型として，pulmonary tumor thrombotic microangiopathyを報告した。血管病変の首座が肺小動脈及び細動脈にあり，血管病変の首座が肺小動脈および細動脈にあるものを新たな疾患概念として確立し，pulmonary tumor thrombotic microangiopathy（PTTM）と呼称した 2。血管内腫瘍塞栓に加えて内膜の線維性肥厚および血栓の器質化と再疎通を伴っていることが特徴的である。本症例においても血管径約200μm以下の細動脈を中心に，これらの組織所見が確認できたことよりPTTMとの診断に至った。 PTTMにおける肺血管内腔狭窄の病因として，腫瘍細胞から分泌されるVEGF 3，FGF，OPN 3，PDGF 4などの成長因子群により内膜の線維細胞増生が誘導される機序が推定されている 5。我々の免疫組織学的な検索においても，肺血管内の腫瘍細胞に同因子群の発現が確認された。これらの成長因子群は血中での上昇が認められず，肺血管内で局所的に作用してPTTMを誘導している可能性が示唆された。 臨床的には呼吸困難，咳嗽，全身倦怠感等を主訴とする予後不良な病態である。山口らは，無症候のうちに微小な肺動脈の腫瘍塞栓を繰り返すことで血管内膜の肥厚や線維化を来し，ある閾値を超えてから肺高血圧症の症状が出現すると示唆している 6。我々が調べた限りでは，本邦におけるPTTMの症例報告は医学中央雑誌で27編30症例存在する。このうち，死亡経過が明記された24例の入院後生存期間は14.9日であった。24例中16例が7日以内に死亡しており，PTTMは入院管理が必要となる病態から死亡に至るまでは急速に病勢が進行していくものと考えられる。本症例では，前医入院1か月ほど前から労作時呼吸困難感が出現しているため，その時期にはPTTMの病態は形成され始めており，低酸素血症が先行する突然の循環虚脱は，既存の肺血管内腔狭窄を基盤にしてびまん性に腫瘍塞栓や血管攣縮が急激に生じて誘導されたものではないかと推測している。 本症例では前医入院中に突然のショックを伴う呼吸不全を呈したことで，まずは急性肺動脈塞栓症を疑ったが造影CT検査により否定された。心エコー検査上では，著明な右心負荷を伴う左心圧排像を示し，左心系への血液流入が抑制されることによるcardiac index（CI）の低下を来していたが，明らかな肺高血圧症を引き起こす左心疾患は指摘できなかった。軽度COPDと診断されていたが，肺炎などCOPDを増悪因子も存在せず，病態が急速進行性であるため慢性呼吸器疾患の進行による肺高血圧症も否定された。一方で本症例では，著明な溶血所見を伴っていたことが特徴的であった。肺高血圧所見を検査上得るまでは，敗血症に伴う一連の全身症状と考えて治療の初期対応を行ったが，結果的には各種培養と病理所見からは本病態における感染症の関与は指摘できなかった。また，自己免疫機序により肺高血圧症，溶血性貧血等の全身症状が急速に出現した可能性も考えられたが，前医までは基盤となる自己免疫疾患を示唆する所見や自己免疫を賦活化させる感染，薬剤投与等のエピソードが無く，実際に特異的な組織学的炎症所見も得られなかった。結果的に，溶血性要因はPTTMを基礎とした肺血管内狭窄による機械的な赤血球破壊によるものと明らかになった。我々が検索した国内外のPTTM症例報告でビリルビン値が記載されている14文献のうち，間接型ビリルビンの上昇を認めた症例は4件あるが，それらが溶血性要因によるものであるかどうかは不明であり，病期の進んだPTTMにおいて赤血球破壊が誘導される現象が特徴的な臨床診断としての指標になり得るのかどうかは今後の検討が必要である。 Herbayらは，300例の固形癌患者の剖検所見において21例（7%）でPTTMが存在していたと報告 2している。PTTMの原発腫瘍としては半数以上が胃癌で，肺癌がそれに続いている 2。我々が医学中央雑誌およびPubMedの国内外の症例報告を検索した限りでは，本症例が初めての肝内胆管癌を起因とするPTTMの報告となる。PTTMを引き起こしやすい癌の細胞特性に何らかの共通性がないかを検索することは，PTTMを制御する薬剤の開発を目指す上でも重要と考えられる。残念ながら，現在PTTMに対する根治的治療法は存在しない。一度進行した肺高血圧の症状を呈すると，本症例のように治療抵抗性に一気に病勢が進行し得る疾患である。末期的なPTTMと診断されれば，その予後を考慮した集中治療方針が決定されることもあるであろう。救急・集中治療において，原因不明の肺高血圧症を認知したら，積極的に胆癌の可能性を疑いPTTMの鑑別を行う必要がある。 急速進行性の肺高血圧症にて死亡に至り，肝内胆管癌由来のPTTMとの病理組織診断を得た1例を経験した。 本論文における利益相反はない。

Correlation analysis between cardiac damage and genotype in Duchenne muscular dystrophy

Objective To explore the evolution of Duchenne muscular dystrophy (DMD) patients with cardiac damage. Methods Clinical data of 144 DMD patients who were clearly diagnosed by gene detection were collected and analyzed. According to the results of ultrasonic cardiography, they were divided into cardiac involvement group (N = 50) and non-involvement group (N = 94). The correlation between genotypes and cardiac damage was analyzed. Results Compared with non-involvement group, cardiac involvement group had larger atrium and ventricle ( P < 0.01), thicker posterior wall of left ventricle and interventricular septum ( P = 0.031, 0.001), as well as lower left ventricular ejection fraction ( P = 0.034). In addition, the mutation rates of DMD gene in exon 3 ( P = 0.047), exon 4 ( P = 0.047), exon 21 ( P = 0.047), exon 22 ( P = 0.040) and exon 53 ( P = 0.033) were increased significantly, indicating that mutations had a correlation with cardiac damage. Conclusions The main performance of DMD cardiac damage is dilated cardiomyopathy. It has more possibility to cause cardiac damage when DMD gene mutation is closer to the end of 5'-terminal. DOI: 10.3969/j.issn.1672-6731.2015.06.007