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Background: Prognosis of breast cancer patients has been improved along with the progress in cancer therapies. However, cancer therapeutics-related cardiac dysfunction (CTRCD) has been an emerging issue. For early detection of CTRCD, we examined whether native T1 mapping and global longitudinal strain (GLS) using cardiac magnetic resonance (CMR) and biomarkers analysis are useful., Methods: We prospectively enrolled 83 consecutive chemotherapy-naïve female patients with breast cancer (mean age, 56 ± 13 yrs.) between 2017 and 2020. CTRCD was defined based on echocardiography as left ventricular ejection fraction (LVEF) below 53% at any follow-up period with LVEF>10% points decrease from baseline after chemotherapy. To evaluate cardiac function, CMR (at baseline and 6 months), 12‑lead ECG, echocardiography, and biomarkers (at baseline and every 3 months) were evaluated., Results: A total of 164 CMRs were performed in 83 patients. LVEF and GLS were significantly decreased after chemotherapy (LVEF, from 71.2 ± 4.4 to 67.6 ± 5.8%; GLS, from -27.9 ± 3.9 to -24.7 ± 3.5%, respectively, both P < 0.01). Native T1 value also significantly elevated after chemotherapy (from 1283 ± 36 to 1308 ± 39 msec, P < 0.01). Among the 83 patients, 7 (8.4%) developed CTRCD. Of note, native T1 value before chemotherapy was significantly higher in patients with CTRCD than in those without it (1352 ± 29 vs. 1278 ± 30 msec, P < 0.01). The multivariable logistic regression analysis revealed that native T1 value was an independent predictive factor for the development of CTRCD [OR 2.33; 95%CI 1.15-4.75, P = 0.02]., Conclusions: These results indicate that CMR is useful to detect chemotherapy-related myocardial damage and predict for the development of CTRCD in breast cancer patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The Japanese Network of Cardiovascular Departments for Adult Congenital Heart Disease (JNCVD-ACHD) was founded in 2011 for the lifelong care of adult patients with congenital heart disease (ACHD patients). This network maintains the first Japanese ACHD registry., Methods and Results: From 2011 to 2019, the JNCVD-ACHD registered 54 institutions providing specialized care for ACHD patients in 32 of the 47 prefectures in Japan. The registry collected data on the disease profile for 24,048 patients from 50 institutions and the patient characteristics for 9743 patients from 24 institutions. The most common ACHDs were atrial septal defect (20.5 %), ventricular septal defect (20.5 %), tetralogy of Fallot (12.9 %), and univentricular heart (UVH)/single ventricle (SV; 6.6 %). ACHD patients without biventricular repair accounted for 37.0 % of the population. Also examined were the serious anatomical and/or pathophysiological disorders such as pulmonary arterial hypertension (3.0 %) including Eisenmenger syndrome (1.2 %), systemic right ventricle under biventricular circulation (sRV-2VC; 2.8 %), and Fontan physiology (6.0 %). The sRV-2VC cases comprised congenitally corrected transposition of the great arteries without anatomical repair (61.9 %) and transposition of the great arteries with atrial switching surgery (38.1 %). The primary etiology (86.4 %) for Fontan physiology was UVH/SV. In addition, developmental/chromosomal/genetic disorders were heterotaxy syndromes (asplenia, 0.9 %; polysplenia, 0.7 %), trisomy 21 (4.0 %), 22q11.2 deletion (0.9 %), Turner syndrome (0.2 %), and Marfan syndrome (1.1 %)., Conclusions: Although the specific management of ACHD has systematically progressed in Japan, this approach is still evolving. For ideal ACHD care, the prospective goals for the JNCVD-ACHD are to create local networks and provide a resource for multicenter clinical trials to support evidence-based practice., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Although cardiac troponin and natriuretic peptide have been shown to decrease after balloon pulmonary angioplasty (BPA) with improved right ventricular afterload in chronic thromboembolic pulmonary hypertension (CTEPH), biomarkers to evaluate the effects of BPA independently of heart failure status remain to be developed., Methods: In 39 consecutive CTEPH patients including 31 who underwent BPA, we measured plasma levels of cyclophilin A (CyPA), which we demonstrated is secreted from pulmonary vascular smooth muscle cells in response to mechanical stretch and hypoxia., Results: CyPA levels were elevated in CTEPH patients (12.7, IQR: 7.6-16.0) compared with 8 thromboembolic controls with a history of venous thromboembolism (4.9, IQR: 2.4-11.2) or 18 healthy controls (4.1, IQR: 2.4-6.8) (both p< 0.05) and were linearly correlated with mean pulmonary arterial pressure (r=0.50, p = 0.0003) and pulmonary vascular resistance (r=0.32, p= 0.026). BPA reduced CyPA levels and tended to lower brain-type natriuretic peptide (BNP) levels (p< 0.01 and p = 0.07). When comparing the changes in CyPA before and after BPA in the two subgroups with higher (≥35pg/mL) and normal (<35pg/mL) BNP at baseline, CyPA decreased both in patients with higher BNP and those with normal BNP (both p< 0.05). In contrast, BNP decreased only in patients with higher BNP (p< 0.05). Also, CyPA decreased both in patients with lower (<25 kg/m 2 ) and higher (≥25kg/m 2 ) body mass index (BMI) at baseline (both p<0.05), whereas BPA tended to reduce BNP in patients with lower BMI (p = 0.12) but not in those with higher BMI (p = 0.55)., Conclusions: CyPA could be a useful biomarker to evaluate the effects of BPA even in patients with normal BNP or high BMI., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by organic thrombotic obstructions in the pulmonary arteries with reduced pulmonary vascular reserve. This study aimed to examine whether postural changes in ventilatory gas analysis parameters are useful for assessing pulmonary hemodynamics in patients with CTEPH., Methods: A total of 44 patients with newly diagnosed CTEPH (CTEPH group), 33 patients with improved CTEPH (mean pulmonary arterial pressure [mPAP] <25 mm Hg), and 25 controls were enrolled. Patients with improved CTEPH referred to patients without residual PH who were previously diagnosed with CTEPH and already received optimal therapies. Various pulmonary function parameters were examined in supine and sitting positions, and postural changes were calculated (Δ[supine - sitting]). In 32 patients with CTEPH, we examined hemodynamic and ventilatory gas analysis parameters before the first balloon pulmonary angioplasty (BPA) and during follow-up., Results: Patients with CTEPH had significantly lower supine end-tidal carbon dioxide pressure (P ET CO 2 ) and ΔP ET CO 2 than controls (both P < 0.001), and these parameters were significantly correlated with mPAP (R 2  = 0.507, P < 0.0001 and R 2  = 0.470, P < 0.001, respectively). Supine P ET CO 2 and ΔP ET CO 2 were significantly lower in patients with improved CTEPH than in controls (both P < 0.001). Hemodynamic and echocardiographic parameters were comparable in both groups. Furthermore, significant correlation between the change in mPAP and change in supine P ET CO 2 by BPA was noted (R 2  = 0.478, P < 0.001)., Conclusion: These results indicate that postural changes in ventilatory gas analysis parameters are useful and non-invasive method for the evaluation of mPAP, which is one of the hemodynamic parameters of CTEPH severity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Valve-sparing aortic root replacement is one of the effective repairs for aortic regurgitation resulting from progressive dilatation of the aortic root late after surgical correction of conotruncal anomaly. However, feasibility and effectiveness of this procedure are unknown for unrepaired physiology. A 32-year-old man presented with unrepaired tetralogy of Fallot (TOF) and moderate aortic regurgitation with severe left ventricular dysfunction. Valve-sparing aortic root replacement and TOF repair were simultaneously performed. Six months after the surgical procedure, aortic regurgitation remained trivial. Concomitant valve-sparing aortic root replacement with TOF repair can be feasible and effective for unrepaired TOF with aortic regurgitation., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Pulmonary arterial hypertension after arterial switch operation for transposition of the great arteries is an infrequent but life-threatening complication. We report successful lung transplantation in a case of pulmonary hypertension after arterial switch operation. Cardiopulmonary bypass outflow was established through the right subclavian and femoral arteries because of the previous arterial switch operation. Abnormal anatomy and severe pleural and pericardial adhesions as a result of previous operations resulted in prolonged graft ischemic and operation times. Despite delayed left heart adaptation and primary graft dysfunction requiring prolonged extracorporeal membrane oxygenation, the recipient was eventually discharged without activity limitations., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Recent studies showed that children with univentricular heart have elevated plasma B-type natriuretic peptide (BNP) levels prior to bidirectional cavopulmonary anastomosis (BDCPA). However, it remains to be established whether BNP levels reflect the degree of hemodynamic overload and relate to long-term outcome in univentricular circulation., Methods: Fifty one consecutive children with functionally univentricular heart prior to BDCPA were studied. All patients underwent cardiac catheterization and BNP measurement. Ventricular end-systolic wall stress (ESWS) and end-diastolic wall stress (EDWS) were calculated from cardiac catheterization data., Results: Median age was 1.1 years and 34% were female. Median BNP concentration was 90.4 pg/ml. Patients with high BNP (≥ 100 pg/ml) had higher pulmonary to systemic flow ratio (p = 0.014), a greater end-diastolic volume (p=0.009), more severe atrioventricular valve regurgitation (p= 0.02) and lower ventricular mass to end-diastolic volume ratio (p=0.006). BNP levels strongly related to EDWS (r = 0.75, p< 0.0001) and ESWS (r = 0.63, p < 0.0001). During median follow-up period of 3.2 years, 15 patients died and one underwent heart transplantation for refractory heart failure. On multivariate Cox regression analysis, high BNP concentration was an independent predictor of death or transplantation (HR 3.05, CI: 1.06-8.83, p = 0.04)., Conclusions: High BNP concentration at the first palliative stage towards Fontan circulation reflects high wall stress due to high volume load and insufficient ventricular hypertrophy. Moreover, high BNP levels at this stage were independently related to long-term outcome. BNP may be used as a guide to identify patients with high workload due to inadequate adaptation to hemodynamic load, who are at high risk., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Tachyarrhythmia during pregnancy may have an adverse effect on the mother and the fetus. Heart rate variability (HRV) is a significant marker of autonomic nervous function and may predict tachyarrhythmia. HRV and incidence of arrhythmia in women with repaired congenital heart disease (CHD) during pregnancy were examined., Methods: Twenty-eight patients with repaired CHD (35 pregnancies, age: 26+/-3.5 years at their first pregnancy, 22+/-6.2 years post-repair) and 19 healthy pregnant volunteers (controls, 19 pregnancies, age: 28+/-5.5 years) were enrolled. Holter monitoring and laboratory tests were examined at 28+/-4 weeks of gestation and 22+/-13 weeks postpartum in patients and 28+/-3 weeks of gestation in controls. Time and frequency variables of HRV were analyzed., Results: Compared with controls and postpartum, there was a significantly higher incidence of tachyarrhythmia during pregnancy in women with CHD (4 episodes of supraventricular tachyarrhythmia (SVT) and 5 of non-sustained ventricular tachycardia, P=0.02). HR response in tetralogy of Fallot was impaired (781+/-50 ms, P=0.02). Most of HRV variables were significantly suppressed (average RR 740+/-64 ms, SDRR 99+/-22 ms, low and high frequency domains (341+/-165 ms2 and 256+/-181 ms2) (P<0.05). Reduced SDRR and high frequency domains were observed in patients with tachyarrhythmia. Furthermore, there were increased left ventricular end-diastolic dimensions 48+/-5 mm (P=0.001) and atrial natriuretic peptide levels 33+/-13 pg/ml (P=0.01) in the CHD patients compared with postpartum levels., Conclusions: Impaired autonomic nervous activity, volume overload of the heart and operative scar all play a contributory role in higher incidence of tachyarrhythmia during pregnancy in patients with repaired CHD compared to healthy pregnant controls. Close monitoring of patients with CHD for tachyarrhythmia during pregnancy is, thus, warranted.

A 65-year-old woman with intermediate type atrioventricular septal defect had been undiagnosed until initial presentation with congestive heart failure. She underwent surgery when the ventricular septal defect was found to be restrictive. The atrioventricular valve was similar to the common atrioventricular valve, but was connected to the crest of the ventricular septal defect. Surgery included direct closure of the ventricular septal defect, repair of the cleft in the atrioventricular valve, and ostium primum closure. Postoperative echocardiography indicated successful heart repair. We present a review of rare intermediate type atrioventricular septal defect in the elderly, and we discuss the surgical issues in this case.

A novel gene designated as fragile site-associated (FSA) gene was recently identified by positional cloning from the CHO 1q31 fragile site which plays an important role in regulating amplification of multidrug resistance (mdr1) gene in multidrug-resistant cells. FSA produces a message of approximately 16 kb which encodes an open-reading frame of 5005 amino acids. FSA shares sequence similarity with that in Caenorhabditis elegans lpd-3, a lipid storage gene. Using immunohistochemical staining and RNA in situ hybridization we report here that expression of FSA is associated with developmental programs of spermatogenesis and mammary gland in mice. Real-time RT-PCR results also support the upregulation of FSA expression in mammary gland development. Expression of FSA in many tissues including colon, skin, ovary, prostate, and bladder is mainly in the postmitotic, well-differentiated compartments. Moreover, levels of FSA expression are downregulated in tumors of these tissue origins. These results suggest that FSA also plays important roles in regulating mammalian epithelial growth and differentiation and tumor development.

Objectives: Recent advances in medical and surgical treatment have led to the survival of increasing numbers of adults with congenital heart disease (CHD). However, the social status of these patients remains unknown. This survey investigated the social prospects for adults with CHD, and the limiting factors for social independence., Methods: A written questionnaire on patient characteristics, education, employability, marital status and insurability was designed to define the characteristics of social independence in adults with CHD. Randomly selected adults with CHD were enrolled: 13 patients with cyanotic unrepaired CHD (4 males, 9 females, mean age: 29.8 +/- 10 years, range: 18-56 years) and 102 patients with other CHDs (48 males, 54 females, mean age: 29.5 +/- 10 years, range: 18-74 years)., Results: University of California at Los Angeles functional class I-II was found in 94% of patients, medication in 46%, and hospitalization in 51%. Compared with the data from Japanese general population, study patients had a lower ratio of high school graduates (86% vs 94%), life insurability (51% vs 71%), marital status (31% vs 32%) and employability (82% vs 80%). Patients with unrepaired cyanotic CHD had significantly lower ratio than those with other CHDs (marital status 15%, p = 0.19; employability 40%, p = 0.0003; high school graduates 69%, p = 0.06; life insurability 18%, p = 0.02, respectively)., Conclusions: Factors affecting social independence in adults with CHD were severity of disease, continuing medication, lower level of education, lower self-esteem, and unknown natural history of CHD. To improve social independence in these patients, further development of medical and surgical therapy and more detailed knowledge of the patients, caretakers and society in this field are needed.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been demonstrated to suppress colorectal tumorigenesis. NSAIDs have also been used to treat inflammatory illnesses. However, the underlying mechanisms of action by NSAIDs have not been completely elucidated. In this study, we reported that among the six members of the multidrug resistance protein gene (MRP1 to MRP6) family which encode membrane transporters for a diverse group of antitumor agents, expression of MRP1 and MRP3 but not the others in human colorectal cancer cell lines was induced by sulindac. This induction profile is consistent with the results using prooxidants which produce reactive oxygen species (ROS) and generate oxidative stress as previously reported. Moreover, treatment of colorectal cancer cells with sulindac induced ROS. Suppression of ROS formation by antioxidant N-acetylcysteine (NAC) downregulated the induction of MRP1 and MRP3 expression. Expression of another oxidative stress-sensitive gene, gamma-glutamylcysteine synthetase heavy subunit gene (gamma-GCSh), which encodes the rate-limiting enzyme in glutathione biosynthesis, was also induced by sulindac. However, the suppression of sulindac-induced gamma-GCSh expression by NAC was less sensitive compared with that of MRP1 and MRP3. We also demonstrated that induction of MRP3 and gamma-GCSh was independent of intracellular COX-2 levels. These results, collectively, suggest a ROS-related, COX-2-independent mechanism for the induction of drug resistance gene expression that bears important implications to the roles of NSAIDs in colorectal carcinogenesis and inflammatory response., (©2002 Elsevier Science (USA).)

Background: Spontaneous hemopneumothorax is a rare disorder, occurring in 1% to 12% of patients with spontaneous pneumothorax. We studied our previously treated patients to determine the nature of optimal operative management., Methods: This was a retrospective case study. From 1987 to 1994, of 428 cases of spontaneous pneumothorax that occurred in 234 patients treated at our institution, hemopneumothorax developed in 10 patients (2.3%). The clinical features of these patients were studied., Results: The amount of bleeding ranged from 600 to 1,600 mL, and 3 patients exhibited symptoms of shock, such as sweating, nausea, and syncope. Six patients underwent operation within 7 days from the onset, and this involved resection of the bullae or pneumorrhaphy, or both. The source of bleeding was identified in 5 patients. Pathologic examination showed marked fibrosis with alcian blue-positive deposits of aberrant vessels. All 6 patients continue to be well postoperatively without recurrence or complications. Four patients did not undergo early thoracotomy. However, decortication was required in 3 of these patients because of a reactive fluid collection in the pleural space, which led to impaired lung expansion., Conclusions: Early surgical repair should be considered once diagnosis of a spontaneous hemopneumothorax is confirmed, because this provides better long-term results. Video-assisted thoracoscopic surgery as well as minithoracotomy should be considered as surgical options because of the improved quality of life they confer.

The association between myxomas, spotty pigmentation, and endocrine overactivity is referred to as Carney's complex. This report describes the case of a 24-year-old woman with right atrial myxoma who presented with this association. The patient had a previously excised myxoid tumor of the breast and uneven facial pigmentation was observed, but no evidence of endocrinopathy was detected. The myxoma originated from the right atrial wall adjacent to the junction of the inferior vena cava and right atrium, and was successfully excised. A brief review of Carney's complex is provided after discussion of this rare case.

In 1985, a thoracoscopic technique for closing bullae with hemostatic clips was developed. However, the method was limited, and therefore clinical application was small. A linear endoscopic stapler (Endo-GIA) was developed in 1990. The advent of the Endo-GIA nearly made thoracoscopic treatment of spontaneous pneumothorax practicable, and ended the use of clipping. In addition, a new operative technique was developed, the 3-cm minithoracotomy bullectomy for the treatment of spontaneous pneumothorax. This technique has now become obsolete. The current method is that of a thoracoscopic stapled bullectomy using the Endo-GIA, supported by suturing. The recurrence rate was 2.7% (1/37) using this method. The one recurrence occurred in a case where no bullae were observed during the operation. Our findings suggest that thoracoscopic stapled bullectomy supported by suturing is a practicable treatment of spontaneous pneumothorax. An economical use of the endoscopic stapler and complementary suturing may be less expensive than using a laser. Pleurodesis should be performed in the patients in whom no distinct bullae are discovered thoracoscopically.

The cosmetic deformity of the vertical skin incision for median sternotomy was decreased by using a mechanical traction system to increase exposure at the superior margin of a shorter wound. The limited vertical skin incision did not impede technical surgical maneuvers and produced a scar that was more acceptable than submammary incision or right anterior thoracotomy. The limited skin incision is especially useful in young women with congenital heart disease.

The effectiveness of high-potassium cardioplegic solution in the neonatal heart remains controversial. Our previous study indicated that the protection afforded by a cardioplegic solution was inadequate in the neonatal heart. On the hypothesis that oxyradicals were responsible for the ineffectiveness of cardioplegic solution in neonatal heart, the effects of a cardioplegic solution (a modified St. Thomas' Hospital cardioplegic solution) with recombinant human superoxide dismutase on the isolated perfused neonatal guinea pig hearts (within 2 days after delivery, body weight of 60 to 120 g) were studied in comparison with those on the adult hearts (6 to 8 weeks after delivery, body weight of 300 to 500 g). After arrest induced by modified St. Thomas' Hospital cardioplegic solution, hearts were subjected to 120 min of ischemia at 20 degrees C, during which time the cardioplegic solution was injected every 30 minutes. Then the heart was reperfused for 60 minutes at 37 degrees C. Under this condition, the left ventricular developed pressure recovered to 84.4% +/- 4.0% of the preischemic value in the adult heart, whereas the recovery was only 68.1% +/- 3.1% in the neonatal heart. Thiobarbituric acid-reactive substance level, a parameter of lipid peroxidation by oxyradicals, significantly increased during ischemic arrest both in the adult and neonatal heart. However, the increase was much greater in the neonatal heart than in the adult. Cardioplegia with recombinant human superoxide dismutase (300 and 1,000 U/mL) significantly inhibited this accumulation of thiobarbituric acid-reactive substance in the neonatal heart; at 1,000 U/mL, the myocardial function of the reperfused neonatal heart recovered to the level of the adult heart.(ABSTRACT TRUNCATED AT 250 WORDS)