Hiroshi Mikamo

The clinical course of symptomatic deep vein thrombosis after 3 months of anticoagulant therapy using fondaparinux/edoxaban or fondaparinux/vitamin K antagonist

Background For the management of venous thromboembolism (VTE), providing anticoagulant therapy within the therapeutic range has been a major challenge, as conventional therapy with unfractionated heparin (UFH) and vitamin K antagonist (VKA) requires frequent laboratory monitoring and dose adjustment. Recently, fondaparinux and edoxaban are being used as beneficial alternatives to UFH and VKA. Methods We evaluated the clinical course of symptomatic deep vein thrombosis (DVT) in patients who received the 3-month anticoagulation therapy with fondaparinux/edoxaban (Group A; n=40) in comparison with the findings from our previous experience of patients who received the fondaparinux/VKA combination (Group B; n=33). Results In both Groups A and B, serum D-dimer was significantly improved after treatment (p<0.001). The thrombus volume assessed by quantitative ultrasound thrombosis (QUT) score was significantly reduced in both groups (p<0.001). There was no difference in the proportion of patients who were normalized (ie, disappearance of DVT) between the groups, although Group A had significantly more patients who were normalized or improved (ie, disappearance and reduction of DVT) (p<0.001). No bleeding event was observed in either group. However, in one patient in Group B, worsening of DVT and development of symptomatic PE were observed. Conclusion Fondaparinux/edoxaban therapy is as effective as fondaparinux/VKA. This treatment has the possible advantage in thrombus regression. This would be a beneficial therapeutic option for both patients and physicians.

Susceptibilities of epicardial and subcutaneous fat tissue for browning-gene expression and diet-induced volume reduction are different

The upregulation of brown or brown-like beige adipocytes is a potential strategy for the prevention or treatment of diabetes and coronary artery diseases in obese patients. Epicardial adipose tissue (EAT) differs significantly from subcutaneous fat tissue (SAT) in metabolic properties. To investigate properties of EAT further, thermogenesis gene expression was investigated in human autopsy and murine samples, and adipocytes differentiated from EAT mesenchymal cells. Subsequently, analyzed EAT volume alterations were observed to be associated with weight reduction in obese patients by imaging. Gene expression analyses of autopsy samples revealed that UCP-1 mRNA levels in EAT were significantly increased compared with SAT, and β3-adrenergic receptor (AR) levels tended to be increased; this finding was verified in comparing EAT with SAT in mice. Browning stimulation of human EAT-derived MCs increased uncoupling protein-1 and β3-AR levels by 3.2 fold- and 12.6-fold compared with SAT-derived MCs, respectively. Subsequent imaging for EAT volume measurement using multi-detector computed tomography in 10 obese patients revealed that mean EAT volumes did not significantly decrease following weight loss therapy. The EAT volume alterations were not correlated with weight changes, whereas positive correlations were observed in SAT and visceral adipose tissue. Therefore, the studies in man and mouse on EAT properties demonstrated that susceptibilities of EAT and SAT for browning-gene expression and diet-induced volume reduction were grossly different. The data suggest a potential association of EAT with local thermogenetic and metabolic homeostasis in cardiac and/or cardiovascular cells, in conjunction with systemic energy metabolism.

PS 02-09 Effect of nicorandil administration on arterial stiffness monitored with the cardio-ankle vascular index (CAVI) after coronary intervention

Objective: Nicorandil improves coronary arterial dysfunction and improves clinical outcome in patients with ischemic heart disease. But, the precise mechanism was not fully clarified. Cardio-ankle vascular index (CAVI) represents arterial stiffness of the aorta, femoral artery and tibial artery as a whole, and its feature is independency from blood pressure at measuring time. Then, the effect of intravenous nicorandil on arterial stiffness monitored with CAVI, were studied after percutaneous coronary intervention (PCI) in patients with stable angina pectoris (SAP). Design and Method: Study subjects were 45 consecutive patients with SAP underwent successful PCI. Patients were randomized to the control (n = 15), or nicorandil group (n = 30). In the nicorandil group, nicorandil was administrated over 12 hours after PCI (2 or 4 mg/h). CAVI was measured just after PCI and after administration of nicorandil (every 10 minutes for first 30 minutes, 60 minutes, and over 12 hours later). At the same time, stroke volume was measured using electrical bio-impedance method (Aesculon), and various circulation factors were calculated. Results: CAVI was significantly decrease in nicorandil group (9.90 ± 1.00 to 8.68 ± 1.10, p < 0.05), whereas there were no significantly change in control group (9.71 ± 1.22 to 9.39 ± 1.37, p = 0.30). Systolic blood pressure (sBP) and systemic vascular resistance index (SVRI) were significantly decrease only in nicorandil group (sBP; 146.8 ± 15.2 to 118.9 ± 13.7 mmHg, p < 0.05, SVRI; 3725.5 ± 1076.7 to 2632.8 ± 765.9 dyne sec cm−5, p < 0.05). Cardiac index (CI) increased in nicorandil, but not significant (2.31 ± 0.63 to 2.55 ± 0.60 l/min/m2, p = 0.13). CAVI during nicorandol administration significantly correlated with each factors (vs SBP, r = 0.37, vs SVRI, r = 0.29, vs CI, r = -0.21, p < 0.05 in each). Conclusions: In this study, intravenous administration of nicorandil decrease the arterial stiffness monitored with CAVI, indicating that nicorandil decreased an afterload after successful PCI. Improvement of clinical outcome in patients with ischemic heart disease by nicorandil might be due to a decrease of afterload in addition to improvement of coronary arterial dysfunction.