Yuji Kanaoka

Reconstituted High-Density Lipoprotein Stimulates Differentiation of Endothelial Progenitor Cells and Enhances Ischemia-Induced Angiogenesis

Background—Plasma high-density lipoprotein (HDL) levels have an inverse correlation with incidence of ischemic heart disease as well as other atherosclerosis-related ischemic conditions. However, the molecular mechanism by which HDL prevents ischemic disease is not fully understood. Here, we investigated the effect of HDL on differentiation of endothelial progenitor cells and angiogenesis in murine ischemic hindlimb model. Methods and Results—Intravenous injection of reconstituted HDL (rHDL) significantly augmented blood flow recovery and increased capillary density in the ischemic leg. rHDL increased the number of bone marrow–derived cells incorporated into the newly formed capillaries in ischemic muscle. rHDL induced phosphorylation of Akt in human peripheral mononuclear cells. rHDL (50 to 100 &mgr;g apolipoprotein A-I/mL) promoted differentiation of peripheral mononuclear cells to endothelial progenitor cells in a dose-dependent manner. The effect of rHDL on endothelial progenitor cells differentiation was abrogated by coadministration of LY294002, an inhibitor of phosphatidylinositol 3-kinase. rHDL failed to promote angiogenesis in endothelial NO–deficient mice. Conclusions—rHDL directly stimulates endothelial progenitor cell differentiation via phosphatidylinositol 3-kinase/Akt pathway and enhances ischemia-induced angiogenesis. rHDL may be useful in the treatment of patients with ischemic cardiovascular diseases.

Endotension following endovascular aneurysm repair.

Abstract Endovascular aneurysm repair (EVAR) is a new and minimally invasive alternative to open repair for patients with abdominal aortic aneurysm (AAA). Soon after its introduction in 1990, it was recognized that EVAR had potential and distinct advantages in the elective and emergency settings. However, long-term follow-up has shown enlargement of the AAA in a substantial percentage of patients who underwent EVAR with the original-permeability Excluder. Of interest is that sac expansion frequently occurs in the absence of endoleak, often referred to as endotension. The pathophysiology of endoleak is beginning to be elucidated and its management is ready to be established, while controversy still exists about the etiology and clinical consequences of endotension. Fortunately, the incidence of endotension is decreasing and it appears that AAA expansion after EVAR with the original Excluder can be arrested by endovascular relining with a low-permeability Excluder endoprosthesis. The aim of this brief review is to provide historical perspective and a good understanding of the etiology, diagnosis, and management of endotension.

Secondary interventions following endovascular repair of abdominal aortic aneurysm.

Endovascular aneurysm repair (EVAR) of the abdominal aortic aneurysms is an attractive alternative to open surgery with significantly improved perioperative outcomes. However, EVAR is accompanied by a higher rate of graft-related complications and secondary interventions. Therefore, life-long surveillance and management of secondary treatment is essential for successful EVAR. Endoleaks are one of the most crucial problems after EVAR. Persistent endoleaks are classified into five types and its management depends on the type and severity. Most persistent endoleaks are detectable by contrast-enhanced computed tomography; however, in some cases, two different endoleak types may coexist. Determining whether an endoleak requires any treatment or not is an important consideration. Most if not all type I and III endoleaks require prompt and definitive secondary treatment. While type II endoleaks are most commonly encountered during follow-up, not all type II endoleaks require invasive treatment. When secondary treatment is required, it can be treated endovascularly in most cases, even if there is no endoleak. Following EVAR, due to the decompression of the sac, the integrity of the aneurysmal wall strength reduces. Therefore, sudden sac expansion/rupture may occur when an endoleak is encountered following a period of complete aneurysmal exclusion. If diagnosed promptly most late complications can be treated in a less invasive manner, but it could lead to catastrophic event if it is missed. Therefore, adequate and life-long radiographic follow-up is as important as the appropriate patient and device selection as well as the EVAR procedure itself.

Analysis of Risk Factors for Early Type I Endoleaks After Thoracic Endovascular Aneurysm Repair

Purpose: To evaluate risk factors for early (<30 days) type I endoleak following thoracic endovascular aortic repair (TEVAR). Methods: A retrospective study was conducted of 439 consecutive patients (mean age 74.0±10.0 years; 333 men) who underwent TEVAR at a single center between June 2006 and June 2013. Pathologies included 237 aortic arch aneurysms and 202 descending thoracic aortic aneurysms (dTAA). Maximum TAA diameter was 63.6±13.7 mm. Among the distal aortic arch aneurysms, 124 required coverage of the left subclavian artery (LSA), while the remaining 113 arch aneurysms had debranching (n=40), the chimney technique (n=52), and a branched stent-graft (n=13). Eight patients with dilatation of the ascending aorta underwent arch replacement with elephant trunk prior to TEVAR. Predictive factors for type I endoleak were explored in univariate analysis and examined for each outcome using logistic regression models; results are given as the odds ratio (OR) and 95% confidence interval (CI). Results: Among 439 TEVAR cases, 37 (8.4%) had type I endoleaks on imaging at 1 month; 31 were in the 237 arch cases (13.1%). Endoleak investigation by site indicated a low incidence (3.0%) for dTAAs and markedly low (1.4%) in zone 4. Significantly more endoleaks were observed in zones 0–2 than in zone 4 (p<0.001). On univariate analysis, significant associations were found between endoleak and LSA coverage (OR 5.8, 95% CI 2.4 to 14.4, p<0.001), operative time ≥240 minutes (OR 3.7, 95% CI 1.5 to 6.2, p=0.002), and ≥270 mL of contrast (OR 2.8, 95% CI 1.4 to 5.8, p=0.004). Among the aortic branch reconstruction procedures, the chimney technique was the only maneuver associated with a significant risk of endoleak (OR 5.3, 95% CI 2.3 to 11.2, p<0.001). Arch state was not correlated with endoleaks, but ≥38-mm proximal neck diameter (OR 3.6, 95% CI 1.2 to 10.8, p=0.023), stent-graft diameter ≥40 mm (OR 9.9, 95% CI 1.4 to 30.5, p=0.015), and excessively oversized (≥14%) stent-grafts (OR 3.5, 95% CI 1.2 to 10.3, p=0.020) were; the proximal neck length was not correlated with endoleaks if a proximal neck length >10 mm can be secured. Conclusion: Risks for early type I endoleaks after TEVAR for aneurysm were landing zone 0–2, LSA coverage, large proximal neck and stent-graft diameters, excessive oversizing, and the use of the chimney technique.

Outcomes of the Japanese multicenter Viabahn trial of endovascular stent grafting for superficial femoral artery lesions

Objective: The objective of this study was to assess 1‐year safety, efficacy, and invasiveness outcomes of endovascular stent grafting of symptomatic long lesions (≥10 cm) in the superficial femoral artery (SFA) as a substitute for above‐knee open bypass surgery. Methods: This prospective, multicenter (15 hospitals) study assessed heparin‐coated stent grafts for the treatment of long SFA lesions in Japanese subjects with peripheral arterial disease. Inclusion criteria were Rutherford category 2 to 5 symptoms (grade 5 without active infection), ankle‐brachial index ≤0.9, and color flow duplex ultrasound‐assessed SFA lesions with cumulative length ≥10 cm and ≥50% stenosis. Main efficacy and safety outcomes were primary assisted patency and adverse events, respectively. Secondary outcomes included primary patency using the surgical bypass definition, that is, blood flow through a device without requiring target lesion revascularization (TLR) to maintain or to restore flow. For comparison with prior endovascular studies, primary patency‐interventional was defined as peak systolic velocity ratio <2.5 without TLR in treated lesions. Other outcomes included freedom from TLR and Vascular Quality of Life questionnaire scoring. General anesthesia avoidance and hospitalization duration were compared with historical data from 68 consecutive patients (n = 51 Rutherford 2/3 claudicants and 17 Rutherford 4/5 subjects) who underwent above‐knee bypass surgery at study sites between 2002 and 2012 and met study enrollment criteria. Results: Of 103 enrollees (74.2 ± 7.0 years old; 17.5% female; 97.1% claudicants), 100 subjects were evaluated through postoperative 12 months. Average lesion length was 21.8 ± 5.8 cm, and 65.7% were totally occluded. The whole‐cohort Kaplan‐Meier estimated primary assisted patency rate was 94.1% (95% confidence interval [CI], 87.3%‐97.3%) at 12 months. The primary patency‐surgical rate was 92.1% (95% CI, 84.8%‐96.0%), the primary patency‐interventional rate was 88.1% (95% CI, 80.0%‐93.1%), and freedom from TLR was 93.1% (95% CI, 86.1%‐96.7%). Mean ankle‐brachial index increased from 0.64 ± 0.12 to 0.98 ± 0.12 at 1 month after intervention and 0.94 ± 0 .17 at 12 months (P < .0001 at both follow‐ups). Target vessel revascularization, major amputation, or death did not occur through postoperative 30 days. No life‐ or limb‐threatening intraoperative or perioperative adverse events and no acute limb ischemia cases were observed during follow‐up. Vascular Quality of Life questionnaire score increased from 58.6% ± 15.7% to 72.9% ± 18.6% at 12 months (P < .0001). No stent fractures were detected. No stent graft participant required general anesthesia, and median postoperative hospital stay was 2.0 days (mean, 3.4 ± 2.9 days) in the Viabahn (W. L. Gore & Associates, Flagstaff, Ariz) claudicant subgroup, values that were significantly lower than the 76.5% general anesthesia rate (P < .0001) and 11.0 days median hospitalization stay (mean, 12.7 ± 5.3 days; P < .0001) in the 51 open bypass claudicant subjects. Conclusions: Stent grafting appears to be a safe and less invasive alternative to above‐knee bypass surgery, providing 88% to 92% primary patency at 12 months in long, complex lesions.

Surgical treatment for a 16-year-old girl with anomalous origin of the right pulmonary artery from ascending aorta

Anomalous origin of the right pulmonary artery is a rare congenital malformation and is usually fatal without early surgical correction. A 16-year-old patient, who had received no previous treatment, demonstrated abnormal findings on ECG. On cardiac catheterization, the pressure in the normally arising left pulmonary artery was found to be greater than the systemic level. Bidirectional shunting across a patent ductus was identified and aortography revealed that the right pulmonary artery arose from the posterior wall of the proximal ascending aorta. The presence of severe pulmonary vascular obstructive disease was anticipated and right lung biopsy was performed. The index of pulmonary vascular disease rating was 2.8 and the Heath-Edwards classification was grade 3. Consequently, we considered that corrective right pulmonary circulation could be maintained after correction, and total correction was performed. The postoperative course was uneventful and the pulmonary artery pressure reduced significantly. Discussion focuses on the surgical indications for such infrequent older cases and we conclude that preoperative lung biopsy is useful in identifying severe pulmonary vascular disease and evaluating indications for surgery.

Multivariate Analysis of Risk Factors of Cerebral Infarction in 439 Patients Undergoing Thoracic Endovascular Aneurysm Repair

AbstractThe aim of the study is to identify the potential risk factors of cerebral infarction associated with thoracic endovascular aneurysm repair (TEVAR).TEVAR was developed as a less invasive surgical alternative to conventional open repair for thoracic aortic aneurysm treatment. However, outcomes following TEVAR of aortic and distal arch aneurysms remain suboptimal. Cerebral infarction is a major concern during the perioperative period.We included 439 patients who underwent TEVAR of aortic aneurysms at a high-volume teaching hospital between July 2006 and June 2013. Univariate and multivariate logistic regression analyses were performed to identify perioperative cerebral infarction risk factors.Four patients (0.9%) died within 30 days of TEVAR; 17 (3.9%) developed cerebral infarction. In univariate analysis, history of ischemic heart disease and cerebral infarction and concomitant cerebrovascular disease were significantly associated with cerebral infarction. “Shaggy aorta” presence, left subclavian artery coverage, carotid artery debranching, and pull-through wire use were identified as independent risk factors of cerebral infarction. In multivariate analysis, history of ischemic heart disease (odds ratio [OR] 6.49, P = 0.046) and cerebral infarction (OR 43.74, P = 0.031), “shaggy aorta” (OR 30.32, P < 0.001), pull-through wire use during surgery (OR 7.196, P = 0.014), and intraoperative blood loss ≥800 mL (OR 24.31, P = 0.017) were found to be independent risk factors of cerebral infarction.This study identified patient- and procedure-related risk factors of cerebral infarction following TEVAR. These results indicate that patient outcomes could be improved through the identification and management of procedure-related risk factors.

Assessment of antithrombotic agents using the platelet aggregation test

Abstract Background: A number of antithrombotic agents are available for use in patients with arteriosclerotic disease. However, no guidelines have been established for their clinical use. Objective: The purpose of this study was to compare the ability of various antithrombotic agents to inhibit experimentally induced platelet aggregation. Methods: Sixteen angina-free patients who had undergone coronary artery bypass surgery >6 months before the start of this trial were studied. After a 4-week washout period, ticlopidine hydrochloride (TIC) 400 mg/d, dipyridamole (DIP) 300 mg/d, cilostazol (CIL) 200 mg/d, trapidil 300 mg/d, beraprost sodium 120 μg/d, aspirin dialuminate (ASP) 81 mg/d, ethyl icosapentate 1800 mg/d, and sarpogrelate hydrochloride (SAR) 300 mg/d were administered orally in sequence for 4 weeks each, and platelet aggregation activity was determined at the end of each 4-week period. There were no washout periods between medications. Adenosine diphosphate (ADP) 2, 5, and 10 μmol/L; arachidonic acid 2 mmol/L; and collagen 2 μg/mL were used as agonists. Results: Medication was discontinued in 5 patients—2 patients while receiving DIP, 2 while receiving CIL, and 1 while receiving SAR—due to subjective symptoms. TIC suppressed platelet aggregation significantly at all 3 doses of ADP ( P P P P P P P Conclusions: These results show that TIC, ASP, and CIL, but not the other 5 agents studied, had a significant antithrombotic effect in this sample of patients, as measured by the platelet aggregation test.

One-year outcomes of the U.S. and Japanese regulatory trial of the Misago stent for treatment of superficial femoral artery disease (OSPREY study)

OBJECTIVE The purpose of this study was to assess the safety and efficacy of the Misago stent (Terumo Corp, Tokyo, Japan) in occlusive and stenotic superficial femoral artery (SFA) disease. METHODS The safety and efficacy of the Misago SFA stent were evaluated prospectively in this initial collaboration trial between Japan and the United States. Because this trial enrolled patients mainly from Japan and the United States and because there is a question as to whether a race difference exists in SFA stent performance, the race difference on outcome was also analyzed. In addition, results were compared with a prior SFA stent trial. RESULTS The Misago stent was implanted in 261 subjects with TransAtlantic Inter-Society Consensus (TASC) type A and type B SFA lesions (201 subjects in the United States, 50 in Japan, 9 in Taiwan, 1 in South Korea). The mean age of the patients was 69.3 ± 10.0 years, and the mean lesion length was 83.8 ± 41.3 mm. The overall 12-month primary patency rate and clinically driven target lesion revascularization were 82.9% and 13.0%, respectively. Regional differences within the Occlusive/Stenotic Peripheral Artery Revascularization Study (OSPREY) and outcomes between U.S. and Asian patients were similar, including primary patency (82.9% vs 83.0%; P = .889), clinically driven target lesion revascularization (13.4% vs 11.7%; P = .829), stent fracture rate (1.3% vs 0.0%; P = 1.000), and stent thrombosis rate (0.5% vs 0.0%; P = 1.000). CONCLUSIONS OSPREY 12-month data showed satisfactory outcome of the Misago stent for the treatment of TASC type A and type B SFA lesions and appears to be comparable to recent stent trials. In addition, the lack of difference in outcome among races supports the value of international trials.

Septal branch right ventricular fistula: a complication in coronary artery snaring

We report a septal branch right ventricular fistula complicated after coronary snaring in coronary artery bypass surgery without aortic cross-clamping. The tip of the needle of the snaring suture is made blunt in order to decrease the risk of mechanical injury, but trauma to the septal branch is possible. This rare complication of snaring should be taken into consideration in performing aortic nonclamping coronary artery bypass surgery.