Autocrine Regulation of Interleukin-6 via the Activation of STAT3 and Akt in Cardiac Myxoma Cells.

Plasma concentrations of a pleiotropic cytokine, interleukin (IL)-6, are increased in patients with cardiac myxoma. We investigated the regulation of IL-6 in cardiac myxoma. Immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR) revealed that IL-6 and its receptors, IL-6 receptor (IL-6R) and gp130, co-existed in the myxoma cells. Myxoma cells were cultured, and an antibody array assay showed that a conditioned medium derived from the cultured myxoma cells contained increased amounts of IL-6. Signal transducer and activator of transcription (STAT) 3 and Akt were constitutively phosphorylated in the myxoma cells. An enzyme-linked immunosorbent assay (ELISA) showed that the myxoma cells spontaneously secreted IL-6 into the culture medium. Real-time PCR revealed that stimulation with IL-6 + soluble IL-6R (sIL6R) significantly increased IL-6 mRNA in the myxoma cells. Pharmacological inhibitors of STAT3 and Akt inhibited the IL-6 + sIL-6R-induced gene expression of IL-6 and the spontaneous secretion of IL-6. In addition, IL-6 + sIL-6R-induced translocation of phosphorylated STAT3 to the nucleus was also blocked by STAT3 inhibitors. This study has demonstrated that IL-6 increases its own production via STAT3 and Akt pathways in cardiac myxoma cells. Autocrine regulation of IL-6 may play an important role in the pathophysiology of patients with cardiac myxoma.

Percutaneous Covered Stenting in Splenic Vein for Left-sided Portal Hypertension Caused by Chronic Splenic Vein Obstruction.

Left-sided portal hypertension (LSPH), an uncommon manifestation of portal hypertension, is characterized by conditions such as isolated gastric varices and splenomegaly, which result from impeded splenic venous drainage in the presence of pancreatic disease. We employed a percutaneous transhepatic technique to achieve regression of isolated gastric varices by implanting a covered stent within a blocked splenic vein and by embolizing the posterior gastric vein and varices using N-butyl-2-cyanoacrylate. We report the successful treatment of stenting for LSPH by the covered stent placement.

Recurrent protein-losing enteropathy complicated by postural right subclavian vein compression and right-sided thoracic duct.

We report the case of a 16-year-old female patient with protein-losing enteropathy that was suspected to be caused by thoracic duct congestion associated with postural compression of right subclavian vein. Non-contrast magnetic resonance lymphangiography showed that the thoracic duct connected to the right-sided venous angle of the right subclavian vein which was obstructed when her right arm was lifted. In this case, comprehensive screening of the lymphatics using non-contrast magnetic resonance lymphangiography, which is a minimally invasive tool with high spatial resolution, was helpful for the recognition of the specific pathophysiology. Learning objective: Lymphatic disorders associated with congenital heart disease can be fatal. The morphology and dysfunction of the lymphatic system are complicated, and when added to the complex hemodynamics inherent to congenital heart disease, the pathophysiology is more difficult to understand. To understand the complexity of the lymphatic disease, it is necessary to learn a systematic diagnostic process of lymphatic disorders. In the present case, it is beneficial to know the usefulness of non-contrast magnetic resonance lymphangiography to screen overall lymphatics.

Diverse distribution patterns of segmental longitudinal strain are associated with different clinical features and outcomes in dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) presents with diverse clinical courses, hardly predictable solely by the left ventricular (LV) ejection fraction (EF). Longitudinal strain (LS) offers distinct information from LVEF and exhibits various distribution patterns. This study aimed to evaluate the clinical significance of LS distribution patterns in DCM. METHODS: We studied 139 patients with DCM (LVEF ≤ 35%) who were admitted for heart failure (HF). LS distribution was assessed using a bull's eye map and the relative apical LS index (RapLSI), calculated by dividing apical LS by the sum of basal and mid-LS values. We evaluated the associations of LS distribution with cardiac events (cardiac death, LV assist device implantation, or HF hospitalization) and LV reverse remodeling (LVRR), as indicated by subsequent LVEF changes. RESULTS: Twenty six (19%) and 29 (21%) patients exhibited a pattern of relatively apical impaired or preserved LS (defined by RapLSI < 0.25 or > 0.75, signifying a 50% decrease or increase in apical LS compared to other segments), and the remaining patients exhibited a scattered/homogeneously impaired LS pattern. The proportion of new-onset heart failure and LVEF differed between the three groups. During the median 595-day follow-up, patients with relatively-impaired apical LS had a higher rate of cardiac events (both log-rank p < 0.05) and a lower incidence of LVRR (both p < 0.01) compared to patients with other patterns. RapLSI was significantly associated with cardiac event rates after adjusting for age, sex, and new-onset HF or global LS. CONCLUSION: DCM patients with reduced EF and distinct distribution patterns of impaired LS experienced different outcomes.

Assessment of renal congestion in a rat model with congestive heart failure using superb microvascular imaging.

PURPOSE: Renal congestion is a therapeutic target in congestive heart failure. However, its detailed evaluation in a clinical setting is challenging. This study sought to assess renal congestion impairment using superb microvascular imaging (SMI), a simple and accessible method. METHODS: Dahl salt-sensitive rats, used as a model for congestive heart failure, underwent central venous pressure (CVP) measurements. Renal congestion was evaluated through measurements of renal medullary pressure (RMP) and assessment of renal perfusion using contrast-enhanced ultrasonography at both the early (control group) and heart failure phases (HF group). All rats were assessed with SMI. The region of interest (ROI) was set in interlobular vessels, interlobar vessels, and a combination of these areas. The area ratio was calculated from the color pixel count in the ROI divided by the total pixel count in the ROI. Intrarenal perfusion index (IRPI) was defined as (maximum area ratio-minimum area ratio) / maximum area ratio. RESULTS: There were no significant differences in renal function and left ventricular ejection fraction between the two groups. CVP, time-to-peak (TTP) in the medulla, and RMP were higher in the HF group than in the control group. In the HF group, IRPI, evaluated in the interlobular vessels, was significantly higher than in the control group. IRPI was positively correlated with TTP in the medulla (p = 0.028, R = 0.60) and RMP (p < 0.001, R = 0.84), indicating that IRPI reflected renal congestion. CONCLUSIONS: IRPI is a useful tool for assessing renal congestion in rats with congestive heart failure.

Metabolic remodeling and calcium handling abnormality in induced pluripotent stem cell-derived cardiomyocytes in dilated phase of hypertrophic cardiomyopathy with MYBPC3 frameshift mutation.

Hypertrophic cardiomyopathy (HCM) is an inherited disorder characterized by left ventricular hypertrophy and diastolic dysfunction, and increases the risk of arrhythmias and heart failure. Some patients with HCM develop a dilated phase of hypertrophic cardiomyopathy (D-HCM) and have poor prognosis; however, its pathogenesis is unclear and few pathological models exist. This study established disease-specific human induced pluripotent stem cells (iPSCs) from a patient with D-HCM harboring a mutation in MYBPC3 (c.1377delC), a common causative gene of HCM, and investigated the associated pathophysiological mechanisms using disease-specific iPSC-derived cardiomyocytes (iPSC-CMs). We confirmed the expression of pluripotent markers and the ability to differentiate into three germ layers in D-HCM patient-derived iPSCs (D-HCM iPSCs). D-HCM iPSC-CMs exhibited disrupted myocardial sarcomere structures and an increased number of damaged mitochondria. Ca2+ imaging showed increased abnormal Ca2+ signaling and prolonged decay time in D-HCM iPSC-CMs. Cell metabolic analysis revealed increased basal respiration, maximal respiration, and spare-respiratory capacity in D-HCM iPSC-CMs. RNA sequencing also showed an increased expression of mitochondrial electron transport system-related genes. D-HCM iPSC-CMs showed abnormal Ca2+ handling and hypermetabolic state, similar to that previously reported for HCM patient-derived iPSC-CMs. Although further studies are required, this is expected to be a useful pathological model for D-HCM.

Effectiveness of Embolization for Pulmonary Arteriovenous Malformations from Distal of the Last Normal Branch of the Pulmonary Artery.

Purpose: This retrospective study of patients with pulmonary arteriovenous malformations aims to assess the efficacy of embolization distal to the origin of the last normal branch of the pulmonary artery. Material and Methods: A total of 30 consecutive patients with 38 untreated pulmonary arteriovenous malformations underwent coil embolization distal to the origin of the last normal branch of the pulmonary artery between September 2015 and October 2021. The median (interquartile range) age of patients (5 males, 25 females) was 59 years (50-68 years old), and the median (interquartile range) sizes of the feeding artery and sac were 2.9 mm (2.3-3.8 mm) and 6.7 mm (5.4-9.7 mm), respectively. The technical success rate, persistence rate, and treatment-related complications were evaluated. Technical success was defined as the inability to identify the draining vein on feeding arteriography after coil embolization. Persistence was assessed using time-resolved magnetic resonance angiography. Results: Coil embolization was successful in all patients (100%). There was no persistence during a median (interquartile range) follow-up period of 23 months (10-45 months) for the 38 pulmonary arteriovenous malformations embolized with coils. No major complications were reported. Only minor complications following embolization occurred in 4 of 36 sessions, including local pain in 2 sessions (6%) and hemosputum in 2 sessions (6%). Conclusions: Embolization distal to the origin of the last normal branch of the pulmonary artery is effective in preventing the persistence of pulmonary arteriovenous malformations.

Association Between Right Bundle Branch Block and Ventricular Arrhythmia in Patients With Cardiac Sarcoidosis.

Background: Ventricular arrhythmia (VA) is a life-threatening condition associated with cardiac sarcoidosis (CS). Right bundle branch block (RBBB) is a common conduction disorder in CS; however, its association with VA remains unknown. Objectives: This study aimed to investigate the relationship between RBBB and VA in patients with CS. Methods: This was a post hoc analysis of ILLUMINATE-CS (Illustration of the Management and Prognosis of Japanese Patients with Cardiac Sarcoidosis), a multicenter, retrospective, and observational study that evaluated the clinical characteristics and prognosis of CS. Eligible patients were divided into two groups based on the presence or absence of RBBB at the time of diagnosis. The primary outcome was serious ventricular arrhythmia events (SVAEs), defined as a combination of sudden cardiac death and documented ventricular fibrillation, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator therapy. Results: Overall, 312 patients were studied, with 155 (49.7%) patients presenting with RBBB (RBBB group). Patients in the RBBB group had a higher prevalence of basal interventricular septum (IVS) thinning and prominent late gadolinium enhancement in the basal IVS on cardiac magnetic resonance imaging than those in the non-RBBB group. During a median follow-up of 3.0 years (IQR: 1.6-6.0 years), 66 patients experienced SVAE. In multivariable Cox regression analysis, the RBBB group was independently associated with a higher incidence of SVAEs (HR: 1.93 [95% CI: 1.14-3.28]; P = 0.015). Conclusions: In patients with CS, RBBB was an independent predictor of SVAEs, which might reflect the specific scar distribution that is predominant in the IVS.