Yoshiro Tanaka

Background: Coronary artery fistula (CAF) is an uncommon congenital heart disease (CHD). Most patients are asymptomatic, and CAFs are typically discovered incidentally on echocardiography or computed tomography coronary angiography (CTCA). Although previous reports have suggested an association between CAF and infective endocarditis, there are few reports on the coexistence of CAF and tricuspid valve infective endocarditis (TVIE). We report a rare case where a CAF was identified as the underlying CHD in TVIE using multimodal imaging. Both the CAF and TVIE were successfully treated surgically. Case summary: A Japanese woman in her 40 s who presented with a fever of 38°C that persisted for 4 days. Streptococcus oralis was isolated from two sets of blood cultures obtained on admission. Tricuspid valve vegetation was detected using transthoracic echocardiography, and a CAF, which originated from the right coronary artery (RCA) and terminated in the right atrium (RA), was detected by CTCA. Furthermore, the CAF and turbulent shunt flow directed towards the tricuspid valve were identified on transoesophageal echocardiography and subsequently confirmed as an RCA–RA fistula on coronary angiography. After antibiotic therapy, the patient underwent vegetation resection, tricuspid valve annuloplasty, and CAF excision. Discussion: Careful investigation of the underlying CHD is necessary when TVIE is found. In patients with TVIE, multimodal imaging is useful for investigating underlying CAF and the direct association between TVIE and CAF. When multimodal imaging suggests a direct association between CAF and TVIE, surgical resection of both the TVIE and CAF is essential to prevent the recurrence of TVIE.

Increasing evidence suggests natriuretic peptides (NPs) coordinate interorgan metabolic crosstalk. We recently reported exogenous ANP treatment ameliorated systemic insulin resistance by inducing adipose tissue browning and attenuating hepatic steatosis in diet-induced obesity (DIO). We herein investigated whether ANP treatment also ameliorates myocardial insulin resistance, leading to cardioprotection during ischemia–reperfusion injury (IRI) in DIO. Mice fed a high-fat diet (HFD) or normal-fat diet for 13 weeks were treated with or without ANP infusion subcutaneously for another 3 weeks. Left ventricular BNP expression was substantially reduced in HFD hearts. Intraperitoneal-insulin-administration-induced Akt phosphorylation was impaired in HFD hearts, which was restored by ANP treatment, suggesting that ANP treatment ameliorated myocardial insulin resistance. After ischemia–reperfusion using the Langendorff model, HFD impaired cardiac functional recovery with a corresponding increased infarct size. However, ANP treatment improved functional recovery and reduced injury while restoring impaired IRI-induced Akt phosphorylation in HFD hearts. Myocardial ultrastructural analyses showed increased peri-mitochondrial lipid droplets with concomitantly decreased ATGL and HSL phosphorylation levels in ANP-treated HFD, suggesting that ANP protects mitochondria from lipid overload by trapping lipids. Accordingly, ANP treatment attenuated mitochondria cristae disruption after IRI in HFD hearts. In summary, exogenous ANP treatment ameliorates myocardial insulin resistance and protects against IRI associated with mitochondrial ultrastructure modifications in DIO. Replenishing biologically active NPs substantially affects HFD hearts in which endogenous NP production is impaired.

Glucose is an important preferential substrate for energy metabolism during acute coronary syndrome (ACS) attack, although insulin resistance (IR) increases during ACS. Increasing evidence indicates that natriuretic peptides (NP) regulate glucose homeostasis. We investigated possible compensatory actions of NP in collaboration with other neurohumoral factors that facilitate glucose utilization during ACS. The study population consisted of 1072 consecutive cases with ischemic heart disease who underwent cardiac catheterization (ACS, n = 216; non-ACS, n = 856). Among ACS subjects, biochemical data after acute-phase treatment were available in 91 cases, defined as ACS-remission phase (ACS-rem). Path models based on covariance structure analyses were proposed to clarify the direct contribution of B-type NP (BNP) and noradrenaline to glucose and HOMA-IR levels while eliminating confounding biases. In non-ACS and ACS-rem subjects, although noradrenaline slightly increased glucose and/or HOMA-IR levels (P < 0.03), BNP did not significantly affect them. In contrast, in ACS subjects, high noradrenaline was a significant cause of increases in glucose and HOMA-IR levels (P < 0.001), whereas high BNP was a significant cause of decreases in both parameters (P < 0.005). These findings indicate that BNP and noradrenaline coordinately activate glucose metabolism during ACS, with noradrenaline increasing glucose levels, as an energy substrate, while BNP improves IR and promotes glucose utilization.

In addition to the various effects of natriuretic peptides (NPs) on cardiovascular systems, increasing attention is being paid to the possibility that NPs induce adipose tissue browning and activate thermogenic program. We herein established a direct intracellular temperature measurement system using a fluorescent thermoprobe and investigated the thermogenic effects of A-type NP (ANP) on brown adipocytes. The thermoprobe was successfully introduced into rat brown adipocytes, and the temperature dependent change in fluorescence intensity ratio was measured using a fluorescence microscope. After one-hour incubation with ANP, the degree of the change in fluorescence intensity ratio was significantly higher in ANP-treated (P < 0.01) adipocytes compared to untreated controls. The ANP treatment increased uncoupling protein-1 (UCP1) mRNA levels, which is one of the markers of thermogenesis in adipocytes, while the intracellular ATP content was not changed, indicating mitochondrial uncoupled respiration. Intriguingly, these thermogenic actions of ANP were more prominent when brown adipocytes were incubated at 35 °C than at 37 °C. Moreover, the increase in the intracellular temperature and the expression of UCP1 induced by ANP were cancelled by p38MAPK inhibition. Taken together, this study directly demonstrated the thermogenic actions of ANP in brown adipocytes through the use of a novel method of intracellular temperature measurement.

High serum uric acid (UA) level has been assumed to be a risk factor for left ventricular (LV) dysfunction; however, the precise relationship between these conditions has not been fully examined because many confounding factors are associated with UA level. We herein examined the precise relationship by proposing structural equation models. The study population consisted of 1432 cases with ischemic heart disease who underwent cardiac catheterization. Multiple regression analyses and covariance structure analyses were performed to elucidate the cause-and-effect relationship between UA level and LV ejection fraction (LVEF). A path model exploring the factors contributing to LVEF showed that high UA was a significant cause of reduced LVEF (P = 0.004), independent of other significant factors. The degree of atherosclerosis, as estimated by the number of diseased coronary vessels, was significantly affected by high UA (P = 0.005); and the number of diseased coronary vessels subsequently led to reduced LVEF (P < 0.001). Another path model exploring the factors contributing to UA level showed that LVEF was a significant cause of high UA (P = 0.001), while other risk factors were also independent contributing factors. This study clearly demonstrated that there was a close link between high UA and LV dysfunction, which was represented by possible cause-and-effect relationship.

Five cases with eating disorders (one case with anorexia nervosa alone, 4 cases with anorexia nervosa and bulimia nervosa) complicated with schizophrenia and 3 cases of bulimia nervosa complicated with schizophrenia were reported. The eating disorders and schizophrenia were diagnosed according to the diagnostic criteria of DSM-III-R. As to the type of schizophrenia, 4 patients were of an undifferentiated type and 4 cases were of a disorganized type. Regarding the prepsychotic personality, 6 of the 8 cases showed schizothyme personality traits. All the patients showed depressive symptoms which are relatively common in eating disorders. In all the patients, significant social or school life difficulties persisted and a resumption of premorbid functioning was not seen. The possibility of an affinity between anorexia nervosa and schizophrenia was discussed.