Tomoya Masano

Deficiency of Nectin-2 Leads to Cardiac Fibrosis and Dysfunction Under Chronic Pressure Overload

The intercalated disc, a cell-cell contact site between neighboring cardiac myocytes, plays an important role in maintaining the homeostasis of the heart by transmitting electric and mechanical signals. Changes in the architecture of the intercalated disc have been observed in dilated cardiomyopathy. Among cell-cell junctions in the intercalated disc, adherens junctions are involved in anchoring myofibrils and transmitting force. Nectins are Ca2+-independent, immunoglobulin-like cell-cell adhesion molecules that exist in adherens junctions. However, the role of nectins in cardiac homeostasis and integrity of the intercalated disc are unknown. Among the isoforms of nectins, nectin-2 and -4 were expressed at the intercalated disc in the heart. Nectin-2–knockout mice showed normal cardiac structure and function under physiological conditions. Four weeks after banding of the ascending aorta, cardiac function was significantly impaired in nectin-2–knockout mice compared with wild-type mice, although both nectin-2–knockout and wild-type mice developed similar degrees of cardiac hypertrophy. Banded nectin-2–knockout mice displayed cardiac fibrosis more evidently than banded wild-type mice. The disruption of the intercalated discs and disorganized myofibrils were observed in banded nectin-2–knockout mice. Furthermore, the number of apoptotic cardiac myocytes was increased in banded nectin-2–knockout mice. In the hearts of banded nectin-2–knockout mice, Akt remained at lower phosphorylation levels until 2 weeks after banding, whereas c-Jun N-terminal kinase and p38 mitogen-activated protein kinase were highly phosphorylated compared with those of wild-type mice. These results indicate that nectin-2 is required to maintain structure and function of the intercalated disc and protects the heart from pressure-overload–induced cardiac dysfunction.

Optical coherence tomography study of chronic-phase vessel healing after implantation of bare metal and paclitaxel-eluting self-expanding nitinol stents in the superficial femoral artery.

BACKGROUND This study aimed to assess chronic-phase suppression of neointimal proliferation and arterial healing following paclitaxel-coated (PTX) and bare metal stent (BMS) implantation in the superficial femoral artery using optical coherence tomography (OCT). METHODS Twenty-five patients with 68 stents underwent an 8-month OCT follow-up. Besides standard OCT variables, neointimal characterization and frequencies of peri-strut low-intensity area (PLIA), macrophage accumulation, and in-stent thrombi were evaluated. RESULTS The mean neointimal thickness was significantly less with PTX stents (544.9±202.2 μm vs. 865.0±230.6 μm, p<0.0001). The covered and uncovered strut frequencies were significantly smaller and larger, respectively, in the PTX stent group vs. the BMS group (93.7% vs. 99.4%; p<0.0001, 4.0% vs. 0.4%; p<0.0001, respectively). Heterogeneous neointima was only observed in the PTX stent group (12.5% vs. 0%, p=0.017). The frequencies of PLIA and macrophage accumulation were significantly greater in the PTX stent group (87.2% vs. 67.6%, p=0.001 and 46% vs. 9.1%, p=0.003, respectively). CONCLUSION After 8 months, reduced neointimal proliferation was observed with PTX stent implantation. On the other hand, delayed arterial healing was observed compared with BMS.

A case of an ablation catheter entrapped in the pulmonary vein during atrial fibrillation ablation requiring open heart surgery for removal

Case Report A 64-year-old woman with a 3-year history of drug refractory paroxysmal atrial fibrillation was referred to our hospital for catheter ablation. Preprocedual echocardiography and enhanced computed tomography (CT) revealed no structural heart disease or anatomic anomalies (Figure 1A). Catheter ablation of the atrial fibrillation was performed under conscious sedation. Two 8.5-F long sheaths, an 8-F long sheath, and a 6-F short sheath were introduced percutaneously via the right femoral vein. A 6-F venous sheath was introduced via the right internal jugular vein. A decapolar electrode catheter was positioned in the right ventricular apex. A duodecapolar electrode catheter was advanced into the coronary sinus. A transseptal puncture was performed with the assistance of intracardiac echocardiography using a radiofrequency needle (Japan Lifeline, Tokyo, Japan). Three long sheaths were advanced into the left atrium through the same puncture site. Pulmonary vein (PV) and left atrial angiogram revealed no anatomic anomalies, and the sheaths were placed into the superior PVs. Two circular mapping catheters were positioned in the PVs. An ablation catheter (Thermocool Smart Touch, Biosense Webster, Diamond Bar, CA) was inserted into the 8.5-F sheath placed in the right superior PV. The ablation catheter was pulled back and moved to start the ablation. The operator intended to place the ablation catheter into the left PV and pushed the

Potent effect of prasugrel on acute phase resolution of intra-stent athero-thrombotic burden after percutaneous intervention to acute coronary syndrome

BACKGROUND Recent studies suggested protruding thrombus and atheroma after stent placement could be a substrate for subsequent adverse ischemic events. Although protruded atherothrombotic burden can be assessed as intra-stent tissue (IST) by optical coherence tomography (OCT), the effects of potent antiplatelet therapy on the acute phase resolution of IST in patients with acute coronary syndrome (ACS) was unknown. METHODS Ninety-six consecutive ACS patients with multi-vessel disease were enrolled in this prospective registry. In combination with aspirin, either clopidogrel or prasugrel was selected according to the date of enrolment. OCT examination was done immediately after percutaneous coronary intervention (post-PCI) and 10 days after index PCI (follow-up acute phase) to calculate averaged IST score as semi-quantitative measures of IST. High residual platelet reactivity (HRPR) was defined as platelet reactivity units (PRU)≥240 by VerifyNow P2Y12 assay (Accumetrics Inc., San Diego, CA, USA). RESULTS Thirty two patients (38 stents) were enrolled in the prasugrel group and sixty four patients (72 stents) in the clopidogrel group. Averaged IST scores post-PCI were similar between the two groups (0.68±0.41 vs. 0.68±0.40, p=0.99), which decreased in all of the prasugrel group and in 87.5% of the clopidogrel group (p=0.02). Consequently, changes in averaged IST score (delta averaged IST score) were significantly greater in the prasugrel group compared to those in the clopidogrel group (-0.411±0.288 vs. -0.299±0.270, p=0.045). The frequency of HRPR was significantly lower in the prasugrel group (10.0% vs 32.4%, p=0.028). CONCLUSIONS Prasugrel plus aspirin achieved greater acute phase reduction of IST than clopidogrel plus aspirin, which might underlie the clinical benefit of potent antiplatelet therapy in ACS. (UMIN000018751).