Shuichiro Takanashi

Coronary Atherosclerosis Is Associated With Macrophage Polarization in Epicardial Adipose Tissue

OBJECTIVES The purpose of this report was to assess the link between macrophage polarization in epicardial adipose tissue and atherosclerosis in patients with coronary artery disease (CAD). BACKGROUND Macrophage accumulation enhances chronic inflammation in adipose tissue, but macrophage phenotypic change in human epicardial adipose tissue and its role in atherogenesis are unknown. METHODS Samples were obtained from epicardial and subcutaneous adipose tissue during elective cardiac surgery (CAD, n = 38; non-CAD, n = 40). Infiltration of M1/M2 macrophages was investigated by immunohistochemical staining with antibodies against CD11c and CD206, respectively. Expression of pro- and anti-inflammatory adipocytokines in adipose tissue was evaluated by real-time quantitative polymerase chain reaction. RESULTS Infiltration of macrophages and expression of pro- and anti-inflammatory cytokines were enhanced in epicardial fat of patients with CAD compared with that in non-CAD patients (p < 0.05). The ratio of M1/M2 macrophages was positively correlated with the severity of CAD (r = 0.312, p = 0.039). Furthermore, the expression of pro-inflammatory cytokines was positively correlated, and the expression of anti-inflammatory cytokines was negatively correlated with the ratio of M1/M2 macrophages in epicardial adipose tissue of CAD patients. By contrast, there was no significant difference in macrophage infiltration and cytokine expression in subcutaneous adipose tissue between the CAD and non-CAD groups. CONCLUSIONS The ratio of M1/M2 macrophages in epicardial adipose tissue of CAD patients is changed compared with that in non-CAD patients. Human coronary atherosclerosis is associated with macrophage polarization in epicardial adipose tissue.

Epicardial Adipose Tissue Volume and Adipocytokine Imbalance Are Strongly Linked to Human Coronary Atherosclerosis

Objective—The impact of epicardial adipose tissue (EAT) over abdominal or overall adiposity on coronary artery disease (CAD) is currently unknown. We compared the association among EAT volume (EATV), cytokine/adipocytokine profiles in EAT and subcutaneous fat, and atherogenic CAD. Approach and Results—Paired samples were obtained from EAT and subcutaneous adipose tissue during elective cardiac surgery for CAD (n=50) or non-CAD (n=50). EATV was the sum of cross-sectional EAT areas, and visceral and subcutaneous fat areas were determined at the umbilicus level on computed tomography scans. CD68+, CD11c+, and CD206+ cells were counted using immunohistochemical staining. Cytokine/adipocytokine expression was evaluated using quantitative real-time polymerase chain reaction. Multivariate analysis indicated that male sex, age, diabetes mellitus, high triglycerides, and low high-density lipoprotein cholesterol, and EATV index (EATV/body surface area, cm3/m2) were significant CAD predictors (corrected R2=0.401; P<0.001); visceral fat area, hypertension, smoking, low-density lipoprotein cholesterol (140 mg/dL [3.63 mmol/L]) or statin use were not predictors. The EATV index positively correlated with the CD68+ and CD11c+ cell numbers and nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3), interleukin-1&bgr;, and interleukin-1R expression; and negatively correlated with adiponectin expression in EAT. A multivariate analysis model, including CD68+ cells and interleukin-1&bgr;, and adiponectin expression in EAT strongly predicted CAD (corrected R2=0.756; P<0.001). Conclusions—EATV and macrophage and cytokine/adipocytokine signals in EAT strongly correlated with CAD. Our findings suggest that EATV and adipocytokine imbalance are strongly linked to human coronary atherosclerosis.

Perivascular adipose tissue-secreted angiopoietin-like protein 2 (Angptl2) accelerates neointimal hyperplasia after endovascular injury

Much attention is currently focused on the role of perivascular adipose tissue in development of cardiovascular disease (CVD). Some researchers view it as promoting CVD through secretion of cytokines and growth factors called adipokines, while recent reports reveal that perivascular adipose tissue can exert a protective effect on CVD development. Furthermore, adiponectin, an anti-inflammatory adipokine, reportedly suppresses neointimal hyperplasia after endovascular injury, whereas such vascular remodeling is enhanced by pro-inflammatory adipokines secreted by perivascular adipose, such as tumor necrosis factor-α (TNF-α). These findings suggest that extent of vascular remodeling, a pathological process associated with CVD development, depends on the balance between pro- and anti-inflammatory adipokines secreted from perivascular adipose tissue. We previously demonstrated that angiopoietin-like protein 2 (Angptl2), a pro-inflammatory factor secreted by adipose tissue, promotes adipose tissue inflammation and subsequent systemic insulin resistance in obesity. Here, we examined whether Angptl2 secreted by perivascular adipose tissue contributes to vascular remodeling after endovascular injury in studies of transgenic mice expressing Angptl2 in adipose tissue (aP2-Angptl2 transgenic mice) and Angptl2 knockout mice (Angptl2(-/-) mice). To assess the role of Angptl2 secreted by perivascular adipose tissue on vascular remodeling after endovascular injury, we performed adipose tissue transplantation experiments using these mice. Wild-type mice with perivascular adipose tissue derived from aP2-Angptl2 mice exhibited accelerated neointimal hyperplasia after endovascular injury compared to wild-type mice transplanted with wild-type tissue. Conversely, vascular inflammation and neointimal hyperplasia after endovascular injury were significantly attenuated in wild-type mice transplanted with Angptl2(-/-) mouse-derived perivascular adipose tissue compared to wild-type mice transplanted with wild-type tissue. RT-PCR analysis revealed that mouse Angptl2 expression in perivascular adipose tissue was significantly increased by aging, hypercholesterolemia, and endovascular injury, all risk factors for coronary heart disease (CHD). Immunohistochemical and RT-PCR analysis of tissues from patients with CHD and from non-CHD patients indicated that ANGPTL2 expression in epicardial adipose tissue was unchanged. Interestingly, that analysis also revealed a positive correlation in ANGPTL2 and ADIPONECTIN expression in epicardial adipose tissue of non-CHD patients, a correlation not seen in CHD patients. However, in epicardial adipose tissue from CHD patients, ANGPTL2 expression was positively correlated with that of TNF-α, a correlation was not seen in non-CHD patients. These findings suggest that pro-inflammatory adipokines cooperatively accelerate CHD development and that maintaining a balance between pro- and anti-inflammatory adipokines likely protects non-CHD patients from developing CHD. Overall, our studies demonstrate that perivascular adipose tissue-secreted Angptl2 accelerates vascular inflammation and the subsequent CVD development.

Extensive Reconstruction of the Left Anterior Descending Coronary Artery With an Internal Thoracic Artery Graft

BACKGROUND Revascularization of the diffusely diseased coronary artery is a big challenge for both cardiologists and cardiac surgeons. Long reconstruction of the diffusely diseased vessel may be a useful surgical option. The aim of this study is to assess clinical and angiographic outcomes of extensive reconstruction (≥4 cm) of the left anterior descending coronary artery (LAD) using an internal thoracic artery (ITA) graft with or without endarterectomy. METHODS We retrospectively reviewed 213 patients who underwent extensive reconstruction of the LAD using an ITA graft between September 2004 and July 2009. The diffusely diseased LAD was extensively incised, additional endarterectomy was performed if necessary, and then the LAD was reconstructed with an ITA graft in a long on-lay fashion. Early and 1-year postoperative angiography was performed in 188 patients (88.3%) and 152 patients (71.4%), respectively. RESULTS The mean length of the reconstructed LAD was 5.4 ± 1.2 cm. Endarterectomy was performed in 46.0% of the patients. The operative mortality was 1.4%. Low cardiac output and perioperative myocardial infarction were observed in 3.3 and 5.2% of the patients, respectively. Freedom from death and other cardiac or cerebrovascular events was 91.5 ± 2.2% at 3 years. The early and 1-year patency rates of the ITA to LAD grafting were 95.7% and 93.4%, respectively. CONCLUSIONS Extensive reconstruction of the diffusely diseased LAD using an ITA graft could be performed safely. Early and 1-year angiographic outcome were excellent. This surgical revascularization is an useful option for revascularization of the diffuse coronary artery disease.

Influence of carotid artery stenosis on stroke in patients undergoing off-pump coronary artery bypass grafting

OBJECTIVE It is well known that the presence of carotid artery stenosis increases the risk of perioperative stroke in patients undergoing cardiac surgery with cardiopulmonary bypass. Although off-pump coronary artery bypass grafting (CABG) can avoid the adverse effects of cardiopulmonary bypass, the influence of carotid artery stenosis on the incidence of stroke in patients undergoing off-pump CABG has not been well clarified. METHODS We conducted a retrospective study of 461 patients who underwent elective off-pump CABG after screening for carotid artery stenosis at our institute between September 2004 and May 2007. The incidence and etiologies of stroke were identified. Preoperative screening revealed significant carotid artery stenosis in 49 patients. Clinical results were compared between patients with and without carotid artery stenosis. RESULTS Postoperative stroke occurred in two (0.43%) of the 462 study patients, and in-hospital mortality occurred in three (0.65%). Stroke was due to decreased perfusion resulting from hypovolemic shock in one and thrombosis in the other. There was neither stroke nor in-hospital mortality in patients with carotid artery stenosis, although there were two strokes (0.49%) and three in-hospital mortalities (0.73%) in patients without carotid artery stenosis. CONCLUSIONS The influence of carotid artery stenosis on the incidence of perioperative stroke may be little in off-pump CABG, especially in patients with moderate carotid artery stenosis.

Coronary artery bypass surgery versus percutaneous coronary artery intervention in patients on chronic hemodialysis: does a drug-eluting stent have an impact on clinical outcome?

Abstract  Coronary revascularization methods continue to be refined, and the emergence of the drug‐eluting stent (DES) has especially changed clinical practice related to ischemic heart disease. For chronic hemodialysis (HD) patients, however, the impact of DES on clinical outcome is yet to be determined. Forty‐six consecutive chronic HD patients who underwent myocardial revascularization in our institute were retrospectively reviewed. Twenty‐eight patients underwent coronary artery bypass surgery (CABG) and 18 patients underwent percutaneous coronary artery intervention (PCI). Patient characteristics were similar between the two groups. In the CABG group, bilateral internal thoracic artery (ITA) bypass grafting was performed in 27 patients and off‐pump CABG was performed in 20 patients. In the PCI group, a DES was used in 12 patients. The number of coronary vessels treated per patient was higher in the CABG group (CABG: 4.25 ± 1.32 vs. PCI: 1.44 ± 0.78; p < 0.001). Two‐year survival rates were similar between the two groups (CABG: 94.1% vs. PCI: 73.9%; p = 0.41), but major adverse cardiac event‐free survival (CABG: 85.9% vs. PCI: 37.1%; p = 0.001) and angina‐free survival (CABG: 84.9% vs. PCI: 28.9%; p < 0.001) rates were significantly higher in the CABG group. The one‐year patency rate for the CABG grafts was 93.3% (left ITA: 100%, right ITA: 84.6%, sapenous vein: 90.9%, gastro‐epiploic artery: 100%), and six‐month restenosis rate for PCI was 57.1% (balloon angio‐plasty: 75%, bare metal stent 40%, DES: 58.3%). Even in the era of DES, clinical results favored CABG. The difference in clinical results is due to the sustainability of successful revascularization.

Increased Graft Occlusion or String Sign in Composite Arterial Grafting for Mildly Stenosed Target Vessels

BACKGROUND Composite grafting is a useful technique that avoids the need for aortic manipulation and enables a wide range of target vessels to be revascularized, effectively using the limited arterial grafts available. However, it has not been clarified whether composite grafting can achieve angiographic outcomes equivalent to those obtained with individual grafting for specific target vessels. METHODS We retrospectively reviewed 830 distal arterial graft anastomoses in 256 patients who underwent off-pump coronary artery bypass surgery and also underwent 1-year follow-up coronary angiograms. Four hundred and ten anastomoses using a composite grafting technique were compared with 420 anastomoses using individual grafting. RESULTS In target vessels with mild stenosis, the incidence of graft occlusion or string sign was significantly higher in composite internal thoracic arteries (ITA) than in individual ITA grafts (composite 20.3% versus individual 7.3%; p = 0.018) and showed a higher tendency in composite radial arteries (RA) than in individual RA grafts (59.3% versus 36.4%, p = 0.09). In contrast, the incidence was similar between composite and individual ITA grafts (5.7% versus 3.3%, p = 0.278) and composite and individual RA grafts (11.5% versus 29.6%, p = 0.297) in target vessels with severe stenosis. CONCLUSIONS The angiographic outcomes of composite grafts were closely related to the severity of stenosis of the target coronary artery. In target vessels with mild stenosis, composite grafting resulted in a higher incidence of graft occlusion or string sign than individual grafting did.

Graft Selection and One-Year Patency Rates in Patients Undergoing Coronary Artery Bypass Grafting

BACKGROUND The aim of this study was to assess the angiographic patency rates of grafts used for coronary artery bypass surgery. METHODS We reviewed the records of 930 patients who underwent isolated coronary artery bypass grafting between September 2004 and June 2009. Of these patients, 95.1% underwent off-pump coronary artery bypass grafting. Early and 1-year angiographic patency rates of grafts were assessed. RESULTS Mean anastomoses per patient were 4.0 +/- 1.3. Operative mortality was 0.5%. Stroke occurred in 2.2% of patients, and 1.3% had mediastinitis. Early and 1-year patency rate of total grafts was 97.4% and 87.5%, respectively. One-year patency rate of the left internal thoracic artery, right internal thoracic artery, radial artery, gastroepiploic artery, and saphenous vein graft was 96.1%, 92.0%, 69.5%, 81.4%, and 82.6%, respectively. One-year patency rates of in situ and free right internal artery graft were not significantly different (p = 0.13). One-year patency rate of the radial artery was significantly worse than that of the free right internal thoracic artery graft (p < 0.01) and saphenous vein graft (p < 0.01). CONCLUSIONS Multiple coronary arterial revascularizations in various combinations of grafts were clinically safe and effective for isolated coronary artery bypass surgery. Bilateral internal thoracic artery grafting for the left coronary artery system was the most reliable strategy as shown by angiographic patency rates.

Outcomes of total arch replacement with stepwise distal anastomosis technique and modified perfusion strategy

OBJECTIVE Total arch replacement has been reported to present high morbidity and mortality. We have introduced a stepwise distal anastomosis technique and modified perfusion strategy, including selective antegrade cerebral perfusion, moderate hypothermia, and separate lower-body perfusion, to minimize organ ischemia and secondary morbidities. We report the operative outcomes of total arch replacement with our modified perfusion strategy. METHODS Between August 2006 and December 2008, 119 patients underwent total arch replacement with the current perfusion strategy. Of these patients, 56 (47%) underwent emergency operation for acute type A aortic dissection (n = 48) or ruptured thoracic aneurysm (n = 8). The mean age of patients was 68 years, and the mean follow-up period was 25 months. We analyzed operative mortality, morbidity, and 4-year survival of this patient group. RESULTS The mean operation, cardiopulmonary bypass, and circulatory arrest times were 313, 183, and 47 minutes, respectively. Operative mortality was 3.4%. Operative mortality of elective cases was 1.6%. The incidences of permanent neurologic deficit, paraparesis, and renal insufficiency were 5.0%, 1.7%, and 7.6%, respectively. Actuarial 4-year survival was 86.5%. CONCLUSIONS Total arch replacement with our modified perfusion strategy has demonstrated low operative mortality and morbidity.

Results of long segmental reconstruction of left anterior descending artery using left internal thoracic artery.

BACKGROUND We performed long segmental reconstruction of the left anterior descending coronary artery (LAD) using the left internal thoracic artery (LITA) in patients with diffusely diseased coronary arteries. Our study investigated short- and long-term outcomes and angiographic results after complete revascularization using this technique. METHODS Between March 1995 and March 2001, 112 patients (mean age 63 years) underwent long segmental LAD reconstruction (≥2 cm) with or without endarterectomy using the LITA. Of these, 68 patients (61%) had a history of old myocardial infarction, 44 (39%) had undergone prior percutaneous coronary intervention, 39 (35%) had unstable angina, and 11 (10%) required preoperative intraaortic balloon pumping. RESULTS The majority of patients (96%) underwent operation under cardiac arrest. All patients underwent a complete revascularization with long segmental LAD reconstruction using the LITA. The average length of arteriotomy was 3.7 cm, and 43 patients (38%) underwent extensive (≥4 cm) LAD reconstruction. Endarterectomy was performed in 37 patients (33%). The early mortality rate was 1.8% (2 of 112). Perioperative myocardial infarction in the LAD territory was 5.4%. The 5- and 10-year survival rates were 91% and 74%, respectively. Freedom from major adverse cardiac events at 10 years was 77%. Early angiography (n = 99) showed a 99% excellent patency rate of the LITA. Midterm (n = 61) and long-term (n = 23) follow-up angiography both showed 100% excellent patency rate of the LITA. CONCLUSIONS Long segmental LAD reconstruction with or without endarterectomy using the LITA provided excellent long-term outcomes and acceptable early operative results, even in patients with diffusely diseased coronary arteries.