Vaporizing thrombus with excimer laser before coronary stenting improves myocardial reperfusion in acute coronary syndrome.

BACKGROUND: Mechanical reperfusion has proven to be an unquestionably superior treatment strategy over that of thrombolytic therapy in patients with acute coronary syndrome (ACS). Excimer laser coronary angioplasty (ELCA) is a unique revascularization device that has a lytic effect on thrombus, in addition to its debulking effect on the atherosclerotic plaque beneath the thrombus. METHODS AND RESULTS: This single-center retrospective analysis consisted of consecutive ACS patients treated with ELCA (n=50) and age- and sex-matched ACS patients treated with manual aspiration (n=48) without use of a distal protection device. Success rate was judged by lesion crossability, procedure complications, and significant reduction of stenosis. Tissue-level perfusion was assessed on antegrade Thrombolysis In Myocardial Infarction (TIMI) flow grade, myocardial blush grade (MBG), and ST-segment elevation resolution (STR). Short-term outcome was evaluated according to occurrence of in-hospital major adverse cardiac events (MACE; myocardial infarction, target lesion revascularization, coronary artery bypass graft, and death). Lesion crossability was higher in the ELCA group than in the aspiration group (96.2% vs. 82.6%, P=0.04). Attainment of TIMI 3 flow (86.0% vs. 68.8%, P=0.04) and MBG 3 (76.0% vs. 54.2%, P=0.02) was also higher in the ELCA group than in the aspiration group. Complete STR was similar between the 2 groups. In-hospital MACE were significantly more frequent in the aspiration group. CONCLUSIONS: ELCA is feasible, safe, and effective for the treatment of patients with ACS and appears to be useful as an adjunctive lesion preparation device.

Guidance of myocardial patterning in cardiac development by Sema6D reverse signalling.

Cardiac chamber formation involves dynamic changes in myocardial organization, including trabeculation and expansion of the compact layer. The positional cues that regulate myocardial patterning, however, remain unclear. Through ligation of the Plexin-A1 receptor, the transmembrane-type semaphorin Sema6D regulates endocardial cell migration. Here, we demonstrate that knockdown of either Sema6D or Plexin-A1 leads to the generation of a small, thin ventricular compact layer and to defective trabeculation. In the heart, expression of the Plexin-A1 extracellular domain alone can rescue the defective trabeculation induced by suppression of Plexin-A1, but not that resulting from defective Sema6D expression. This indicates that reverse signalling by Sema6D occurs within the myocardium. In a ligand-dependent manner, Abl kinase is recruited to the cytoplasmic tail of Sema6D and activated, resulting in phosphorylation of Enabled and dissociation from Sema6D. Constitutive activation of Sema6D signalling enhances the migration of myocardial cells into the trabeculae, whereas inhibition arrests cells within the compact layer. Thus, Sema6D coordinates both compact-layer expansion and trabeculation, functioning as both a ligand and a receptor for Plexin-A1.

Atmospheric sea-salt and halogen cycles in the Antarctic.

Atmospheric sea-salt and halogen cycles play important roles in atmospheric science and chemistry including cloud processes and oxidation capacity in the Antarctic troposphere. This paper presents a review and summarizes current knowledge related to sea-salt and halogen chemistry in the Antarctic. First, presented are the seasonal variations and size distribution of sea-salt aerosols (SSAs). Second, SSA origins and sea-salt fractionation on sea-ice and ice sheets on the Antarctic continent are presented and discussed. Third, we discuss SSA release from the cryosphere. Fourth, we present SSA dispersion in the Antarctic troposphere and transport into inland areas. Fifth, heterogeneous reactions on SSAs as a source of reactive halogen species and their relationship with atmospheric chemistry are shown and discussed. Finally, we attempt to propose an outlook for obtaining better knowledge related to sea-salt and halogen chemistry and their effects on the Antarctic and the Arctic.

Important contributions of sea-salt aerosols to atmospheric bromine cycle in the Antarctic coasts.

Polar sunrise activates reactive bromine (BrOx) cycle on the Antarctic coasts. BrOx chemistry relates to depletion of O3 and Hg in polar regions. Earlier studies have indicated "blowing snow" as a source of atmospheric BrOx. However, surface O3 depletion and BrO enhancement occurs rarely under blowing snow conditions at Syowa Station, Antarctica. Therefore, trigger processes for BrOx activation other than the heterogeneous reactions on blowing snow particles must be considered. Results of this study show that enhancement of sea-salt aerosols (SSA) and heterogeneous reactions on SSA are the main key processes for atmospheric BrOx cycle activation. Blowing snow had Br- enrichment, in contrast to strong Br- depletion in SSA. In-situ aerosol measurements and satellite BrO measurements demonstrated clearly that a BrO plume appeared simultaneously in SSA enhancement near the surface. Results show that surface O3 depletion at Syowa Station occurred in aerosol enhancement because of SSA dispersion during the polar sunrise. Amounts of depleted Br- from SSA were matched well to the tropospheric vertical column density of BrO and BrOx concentrations found in earlier work. Our results indicate that SSA enhancement by strong winds engenders activation of atmospheric BrOx cycles via heterogeneous reactions on SSA.

Continuous ST-Monitoring Function of Implantable Cardioverter Defibrillator Detects Silent Ischemia in Patients With Coronary Artery Disease.

BACKGROUND: Newer implantable cardioverter defibrillators can monitor intracardiac ECGs , but their ability to detect ischemia is unclear. This study investigated the usefulness of implantable cardioverter defibrillators with an ST-monitoring function in coronary artery disease patients. METHODS AND RESULTS: We conducted a prospective study of implantable cardioverter defibrillator patients with the ST-monitoring function. One hundred seventy-three patients who received implantable cardioverter defibrillators for primary or secondary prevention of sudden cardiac death. All patients underwent medical examinations at least every 6 months, with standard 12-lead ECGs and device checks that included analysis of the ST-monitoring function. Myocardial perfusion imaging or coronary angiography was performed during the follow-up. The mean follow-up duration was 23.3±7.7 months. Significant ST changes occurred in 15 patients (8.7%), of whom 14 were asymptomatic. The incidence of angina pectoris was significantly higher in the ST change (+) group than that in the ST change (-) group (28.6% versus 7.2%, P=0.03). In the patients who underwent myocardial perfusion imaging, the sensitivity, specificity, and negative predictive value of the ST-monitoring feature to detect ischemia were 75.0%, 72.5%, and 93.5%, respectively. The sensitivity, specificity, and negative predictive value of the ST-monitoring feature to predict residual stenosis evaluated using coronary angiography were 76.9%, 83.5%, and 97.5%, respectively. The percentage of patients with a septal right ventricular lead was significantly lower in the ST change (+) group than in the ST change (-) group (13.5% versus 33.5%, P=0.01). CONCLUSIONS: If intracardiac ECGs ST changes are detected, it is necessary to use additional modalities even in asymptomatic patients. CLINICAL TRIAL REGISTRATION: URL: upload.umin.ac.jp. Unique identifier: UMIN000011824.

Accuracy of J-CTO Score Derived From Computed Tomography Versus Angiography to Predict Successful Percutaneous Coronary Intervention.

OBJECTIVES: The aim of this study was to compare the ability of conventional versus computed tomography angiography (CTA) to predict procedural success and 30-min wire crossing rates in percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions. BACKGROUND: Coronary CTA can be used to assess the morphology of CTO lesions. METHODS: We examined 205 consecutive patients (218 CTO lesions) who underwent coronary CTA pre-PCI. The J-CTO (Multicenter CTO Registry of Japan) score (the sum of the following 5 binary parameters: blunt proximal cap, calcification, bending >45°, and length of occluded segment >20 mm plus previously failed PCI attempt) was calculated using both CTA and conventional coronary angiography and compared. RESULTS: The median patient age was 69 years (interquartile range: 62 to 75 years), 82.4% were male, and a retrograde approach was attempted in 72 (33.0%) cases. The procedural success rate of the CTO-PCI procedures was 82.6%, and 29.4% of cases achieved 30-min wire crossing. The areas under the curve of the CTA-derived J-CTO score for predicting procedural success and 30-min wire crossing were significantly greater than those derived from conventional angiography (0.855 vs. 0.698; p < 0.001 for procedural success and 0.812 vs. 0.692; p < 0.001, for 30-min wire crossing). In addition, the areas under the curve of CTA-derived evaluations of calcification, bending, and occlusion length were significantly higher than those of derived from angiography for predicting procedural success. CONCLUSIONS: The CTA-derived J-CTO score was a more useful predictor of both procedural success and 30-min wire crossing than the J-CTO score derived from conventional angiography.

Simultaneous occurrence of spontaneous coronary artery dissections of the left anterior descending and right coronary arteries in acute myocardial infarction.

Spontaneous coronary artery dissection (SCAD) is a rare and often fatal cause of ischemic heart disease that occurs predominantly in young or middle-aged patients who are otherwise healthy. Therefore, the accurate diagnosis of SCAD and initiation of appropriate treatment may be life-saving. Although recent case reports have described patients with SCAD who exhibited multiple coronary dissections in addition to the culprit lesion, the authors could not determine whether the multiple dissections occurred simultaneously or at different times. In this report, we describe a case involving the simultaneous occurrence of multiple SCADs in the right coronary artery and left anterior descending artery. Intravascular ultrasound helped us to confirm the diagnosis of multiple SCADs, confirm their simultaneous occurrence, and navigate the guidewire into the true lumen. .

Comparison of real-world clinical outcomes between Cypher- and Taxus-eluting stents: the GARA-GARA study.

To evaluate real-world outcomes of PCI in unselected individuals using sirolimus-eluting (SESs) or paclitaxel-eluting stents (PESs) in a single-center randomized trial. Eight hundred consecutive patients (919 lesions) with coronary artery disease were randomized to receive SES or PES implantation. In-hospital, mid-term, and 1-year clinical and angiographical outcomes in both groups were compared. MACEs were defined as cardiac death, myocardial infarction, CABG and target vessel revascularization (TLR). Follow-up angiography was performed in 80.7% of patients. The baseline clinical characteristics were similar in both groups. Pre- and postprocedural reference vessel diameter, minimum length diameter, and diameter stenosis (%DS) were similar in both groups, as was incidence of in-hospital and mid-term MACEs. SESs significantly reduced the risk of TLR, compared with PESs (SES = 5.5%, PES = 10.5%). The superiority of SESs for TLR was also demonstrated with regard to small vessel lesions (stent diameter <2.5 mm) (SES = 6.0%, PES = 15.9%), whereas larger vessel (stent diameter >2.5 mm) lesions did not differ between groups (SES = 5.3%, PES = 8.4%). The safety and efficacy of both DESs were nearly equivalent. SESs, however, were superior to PESs in reducing mid-term TLR, particularly in the small vessel lesion subsets.

Semaphorin-4A, an activator for T-cell-mediated immunity, suppresses angiogenesis via Plexin-D1.

Originally identified as axon guidance molecules, semaphorins are now known to be widely expressed mediators that play significant roles in immune responses and organ morphogenesis. However, not much is known about the signaling pathways via which they exert their organ-specific effects. Here we demonstrate that Sema4A, previously identified as an activator of T-cell-mediated immunity, is expressed in endothelial cells, where it suppresses vascular endothelial growth factor (VEGF)-mediated endothelial cell migration and proliferation in vitro and angiogenesis in vivo. Mice lacking Sema4A exhibit enhanced angiogenesis in response to VEGF or inflammatory stimuli. In addition, binding and functional experiments revealed Plexin-D1 to be a receptor for Sema4A on endothelial cells, indicating that Sema4A exerts organ-specific activities via different receptor-mediated signaling pathways: via Plexin-D1 in the endothelial cells and via T-cell immunoglobulin and mucin domain-2 in T cells. The effects of Sema4A on endothelial cells are dependent on its ability to suppress VEGF-mediated Rac activation and integrin-dependent cell adhesion. It thus appears that Sema4A-Plexin-D1 signaling negatively regulates angiogenesis.

Dual roles of Sema6D in cardiac morphogenesis through region-specific association of its receptor, Plexin-A1, with off-track and vascular endothelial growth factor receptor type 2.

Semaphorins, originally identified as axon guidance facto s in the nervous system, play integral roles in organogenesis. Here, we demonstrate a critical involvement of Sema6D in cardiac morphogenesis. Ectopic expression of Sema6D o RNA interference against Sema6D induces expansion or narrowing of the ventricular chamber, respectively, during chick embryonic development. Sema6D also exerts region-specific activities on cardiac explants, a migration-promoting activity on outgrowing cells from the conotruncal segment, and a migration-inhibitory activity on those from the ventricle. Plexin-A1 mediates these activities as the major Sema6D-binding receptor. Plexin-A1 forms a receptor complex with vascular endothelial growth factor receptor type 2 in the conotruncal segment or with Off-track in the ventricle segment; these complexes are responsible for the effects of Sema6D on the respective regions. Thus, the differential association of Plexin-A1 with additional receptor components entitles Sema6D to exert distinct biological activities at adjacent regions. This is crucial for complex cardiac morphogenesis.