Postoperative anticoagulation management using subcutaneous unfractionated heparin for a patient with nonbacterial thrombotic endocarditis: a case report.

Nonbacterial thrombotic endocarditis (NBTE) presents nonbacterial vegetation on cardiac valves. NBTE requires appropriate anticoagulant therapy to prevent recurrence after surgery. However, there has not yet been established evidence for anticoagulant therapy in NBTE, and low molecular weight heparin is not approved in Japan. We present a case of NBTE that was successfully managed with anticoagulant therapy using subcutaneous unfractionated heparin. A 59-year-old woman was diagnosed with NBTE on the mitral and tricuspid valve associated with breast cancer, underwent valve replacement. Warfarin and continuous intravenous unfractionated heparin were started. However, disseminated intravascular coagulation occurred after heparin was discontinued. Continuous intravenous unfractionated heparin injection was resumed immediately, and subcutaneous unfractionated heparin was administered before discharge. Postoperative echocardiography revealed no vegetation on the prosthetic valves thereafter. Subcutaneous unfractionated heparin therapy is useful to prevent the recurrence of NBTE as the anticoagulation in outpatients.

Effects of Pemafibrate on Reducing Oxidative Stress and Augmenting Angiogenesis in Ischemic Limb Tissue.

OBJECTIVE: Oxidative damage is observed in the ischemic limbs of patients with arteriosclerosis obliterans. We investigated whether pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, reduced oxidative stress in ischemic limbs and consequently rescued limb damage in model mice. MATERIALS AND METHODS: We surgically induced hind-limb ischemia in mice and orally administered pemafibrate solution (P-05 group, 0.5 mg/kg/day; P-10 group, 1.0 mg/kg/day) or control solution (control group). Seven days after the surgery, differences in reactive oxygen species (ROS) contents, antioxidative enzyme and transcription factor expression, blood flow, and capillary density in ischemic limbs were assessed. RESULTS: Tissue ROS levels were lower in the P-05 and P-10 groups compared with those in the control group. Although the tissue expression levels of nuclear factor-erythroid 2-related factor 2 increased in the P-10 group compared with that in the control group, no corresponding changes were observed in the tissue expression of four antioxidative enzymes. The limb salvage rates and capillary densities in ischemic limbs were higher in the P-05 and P-10 groups than that in the control group. CONCLUSION: Pemafibrate treatment reduced oxidative stress and augmented angiogenesis in ischemic limbs, contributing to prevention of limb damage in mice.

Large Thrombus Entrapped in a Patent Foramen Ovale during Inferior Vena Cava Filter Protection for Venous Thromboembolism.

Background. A large thrombus entrapped in the patent foramen ovale (PFO) is an extremely rare condition. Moreover, it is considered even rarer after temporary inferior vena cava filter (TIVCF) placement for the prevention of fatal pulmonary embolism due to venous thromboembolism (VTE). Case Report. A 58-year-old man presented with syncope following chest pain and dyspnea due to PE exacerbation during TIVCF protection, which then led to cardiogenic shock. Echocardiography revealed a large thrombus entrapped in the PFO, and computed tomography (CT) showed a bilateral pulmonary artery embolism. The patient was treated with open surgical embolectomy for a pulmonary artery thrombus and PFO thrombus with simultaneous closure of the PFO. The patient's postoperative course was uneventful. Results and Conclusion. Surgical embolectomy was useful with respect to the feasibility of resection of both intracardiac thrombus and pulmonary artery thrombus performed simultaneously, contributing to the prevention of systemic embolisms, and echocardiography plays an important role for early diagnosis.

Endovascular Aortic Repair for Heavily Calcified Abdominal Aortic Stenosis Using the Gore Viabahn Vbx Balloon-Expandable Covered Stent.

Open surgery for the treatment of focal infrarenal aortic stenosis in high-risk patients may result in complications and mortality. Endovascular aortic repair may be used to treat these lesions. Here, we present the case of a 78-year-old woman with severe, highly calcified stenosis of the infrarenal abdominal aorta, which was successfully treated with the GORE VIABAHN VBX (Gore Medical; Flagstaff, AZ) balloon-expandable covered stent. Long-term and randomized controlled studies comparing open surgery with EVAR are necessary to evaluate the usefulness of this novel device.

Isolated External Iliac Artery Aneurysm with Fibromuscular Dysplasia.

Isolated aneurysms of the external iliac artery are rare in patients with fibromuscular dysplasia. In this study, we report the case of a 74-year-old man with advanced gastric cancer who was found to have a medium-sized aneurysm of the external iliac artery (35 mm) on preoperative computed tomography angiograms. The patient underwent laparoscopic gastrectomy followed by replacement of the external iliac artery 6 months later. Histological examination of biopsy specimens revealed fibromuscular dysplasia. The 6 month postoperative course was uneventful. Such a case of external iliac artery aneurysm caused by fibromuscular dysplasia is very rare, and open surgery is recommended for its removal.

Impact of the Trifecta bioprosthetic valve in patients with low-flow severe aortic stenosis.

Aortic stenosis (AS) is the most common valve disorder in advanced age. Previous reports have shown that low-flow status of the left ventricle is an independent predictor of cardiovascular mortality after surgery. The Trifecta bioprosthesis has recently shown favorable hemodynamic performance. This study aimed to evaluate the effect of the Trifecta bioprosthesis, which has a large effective orifice area, in patients with low-flow severe AS who have a poor prognosis. We retrospectively evaluated 94 consecutive patients with severe AS who underwent aortic valve replacement (AVR). Patients were divided into two groups according to the stroke volume index (SVI): low-flow (LF) group (SVI < 35 ml/m2, n = 22) and normal-flow (NF) group (SVI ≥ 35 ml/m2, n = 72). Patients' characteristics and early and mid-term results were compared between the two groups. There were no differences in patients' characteristics, except for systolic blood pressure (LF:NF = 120:138 mmHg, p < 0.01) and the rate of atrial fibrillation between the groups. A preoperative echocardiogram showed that the pressure gradient was higher in the NF group than in the LF group, but aortic valve area was similar. The Trifecta bioprosthesis size was similar in both groups. The operative outcomes were not different between the groups. Severe patient-prosthesis mismatch (PPM) (< 0.65 cm2/m2) was not observed in either of the groups. There were no significant differences in mid-term results between the two groups. The favorable hemodynamic performance of the Trifecta bioprosthesis appears to have the similar outcomes in the LF and NF groups. AVR with the Trifecta bioprosthesis should be considered for avoidance of PPM, particularly in AS patients with LV dysfunction.

Use of Edoxaban for the Treatment of Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a life-threatening adverse drug reaction of heparin therapy, which increases a patient's risk of developing venous and/or arterial thromboembolism. HIT should be treated through discontinuation of heparin and administration of nonheparin anticoagulants such as argatroban. For long-term anticoagulation, parenteral nonheparin anticoagulants are generally converted to oral treatment with a vitamin K antagonist such as warfarin. Although administration of warfarin is recommended to overlap with a nonheparin anticoagulant for a minimum of 5 days, overlapping with argatroban and warfarin presents high risks of bleeding. We describe a case of HIT treated with edoxaban. A 78-year-old man underwent surgery for esophageal cancer and was administered heparin perioperatively. After surgery, he was diagnosed with HIT and venous thromboembolism. We immediately stopped heparin and initiated parenteral argatroban. The patient was subsequently started on edoxaban without any overlap between the two drugs. The treatment was successful. The treatment of edoxaban following argatroban for HIT could reduce bleeding complications and shorten the length of hospital stay. To the best of our knowledge, this is the first report of the use of edoxaban for HIT treatment.

The Role of Syk in Inflammatory Response of Human Abdominal Aortic Aneurysm Tissue.

Objective: Inflammatory response is central to pathogenesis of abdominal aortic aneurysm (AAA). Recently, we reported that Syk, a signaling molecule in inflammatory cells, promotes AAA development in a mouse model. In this study, we aimed to investigate the role of Syk in human AAA pathogenesis. Materials and Methods: We obtained human AAA wall samples during open surgical aortic repair at Kurume University Hospital. Immunohistochemical analyses of AAA samples were performed for Syk activation and cell type markers. Ex vivo culture of human AAA tissue was utilized to evaluate the effect of P505-15, a Syk inhibitor, on secretions of interleukin-6 (IL-6) and matrix metalloproteinases (MMPs). Results: Immunohistochemical analysis showed infiltration of B cells, T cells, and macrophages in AAA samples. Syk activation was localized mainly in B cells and part of macrophages. AAA tissue in culture secreted IL-6, MMP-9, and MMP-2 without any stimulation. The unstimulated secretions of IL-6, MMP-9, and MMP-2 were insensitive to P505-15. Secretions of IL-6 and MMP-9 were enhanced by exogenous normal human immunoglobulin G (IgG), which was suppressed by P505-15, whereas secretion of MMP-2 was insensitive to IgG or P505-15. Conclusion: These results demonstrate an important role of Syk for IgG-dependent inflammatory response in human AAA.

Aortic valve replacement with or without concomitant coronary artery bypass grafting in very elderly patients aged 85 years and older.

Degenerative aortic stenosis is the most common structural heart valve disease affecting the aging population. Catheter-based heart valve interventions are less invasive and very useful for very elderly patients. However, we often consider open heart surgery for these patients because of anatomical reasons and co-existing cardiac diseases, i.e., severe coronary artery disease. We aimed to analyze the outcomes of very elderly patients aged ≥ 85 years undergoing aortic valve replacement (AVR) with or without coronary artery bypass grafting (CABG). Twenty-nine very elderly patients aged ≥ 85 years who underwent AVR with CABG (n = 11, Group AC) or isolated AVR (n = 18, Group A) were examined. The overall mean age of the patients was 87.2 ± 2.6 (range 85-94) years. The estimated operative mortality rate, calculated using the Japan score, EuroSCORE II, and STS risk score, was 5.72%-10.88% in Group AC and 5.63%-8.30% in Group A. Aortic cross-clamp time (126.5 ± 29.0 vs. 96.9 ± 29.2 min, p = 0.016) was significantly longer in Group AC than in Group A. Although the major morbidity rate was higher in Group AC than in Group A (36% vs. 6%, p = 0.0336), the length of intensive care unit stay and hospital stay was comparable between both groups. There was no 30-day and hospital mortality in both groups. Eleven patients died during follow-up (senility, 5; cerebrovascular events, 2; renal failure, 1; unknown, 3). There were no significant differences in survival rates during follow-up (log-rank p value = 0.1051). The 1-, 2-, 3-, 4- and 5-year survival rates were 91%, 80%, 69%, 69% and 69%, respectively, in Group AC and 94%, 94%, 94%, 94% and 88%, respectively, in Group A. In conclusion, AVR with or without CABG could be safely performed in carefully selected very elderly patients with acceptable early- and long-term results. AVR with CABG in very elderly patients aged ≥ 85 offers similar results to isolated AVR in terms of 30-day mortality, hospital mortality, and long-term survival.

Abdominal Aortic Aneurysm Caused by Aortic Fibromuscular Dysplasia: A Case Report.

Fibromuscular dysplasia (FMD) mainly develops in medium-sized arteries, including renal, extracranial, and extremity arteries, but it rarely causes abdominal aortic aneurysm (AAA). A 69-year-old woman with AAA diagnosed on ultrasonography by a home doctor visited our hospital. Contrast-enhanced computed tomography revealed a saccular aneurysm of terminal abdominal aorta. We performed abdominal aortic replacement and resected the section with aneurysm. Pathological examination of the wall tissue of the resected aneurysm revealed findings that are consistent with FMD. We report this case of AAA caused by aortic FMD because of its rarity.

Cytokine Profile of Human Abdominal Aortic Aneurysm: Involvement of JAK/STAT Pathway.

Objective: Abdominal aortic aneurysm (AAA) is characterized by inflammation and destruction of normal tissue architecture. The present study aimed to evaluate the inflammatory signaling cascade by analyzing the cytokines of AAA tissue. Materials and Methods: We analyzed the comprehensive cytokine secretion profiles of 52 cytokines from human AAA in four patients with AAA using fluorescent beads-based multiplex assay. Further, the effect of janus kinase (JAK) inhibition by pyridone 6 on cytokine profiles was also evaluated. Results: Cytokine secretion profiles were found to be similar among the four patients. A high level of JAK/signal transducers and activator of transcription (STAT) pathway activity in AAA tissue in culture was maintained, which may be attributed to the secretion of endogenous JAK-activating cytokines. Inhibition of JAK by pyridone 6 resulted in the suppression of STAT3 phosphorylation and secretion of a subset of chemokines and JAK-activating cytokines. However, the inhibition of JAK had no effect on the secretion of matrix metalloproteinase (MMP)-2, MMP-9, or TGF-ß family that is responsible for the metabolism of extracellular matrix. Conclusion: The findings of the present study suggested that AAA tissue exhibits a stereotypical profile of cytokine secretion, where JAK/STAT pathway may play a role in regulating a subset of cytokines. Identification of such a cytokine profile may reveal potential diagnostic markers and therapeutic targets for AAA.

Involvement of B Cells, Immunoglobulins, and Syk in the Pathogenesis of Abdominal Aortic Aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a potentially life-threatening disease that is common in older individuals. Currently, therapeutic options are limited to surgical interventions. Although it has long been known that AAA tissue is enriched in B cells and immunoglobulins, their involvement in AAA pathogenesis remains controversial. METHODS AND RESULTS: We investigated the role of B cells and immunoglobulins in a murine model of AAA, induced with a periaortic application of CaCl2, and in human AAA. Both human and mouse AAA tissue showed B-cell infiltration. Mouse AAA tissue showed deposition of IgG and activation of Syk, a key molecule in B-cell activation and immunoglobulin function, which were localized to infiltrating cells including B cells and macrophages. B-cell-deficient muMT mice showed suppression of AAA development that was associated with reduced activation of Syk and less expression of matrix metalloproteinase-9. Administration of exogenous immunoglobulins restored the blunted Syk activation and AAA development in muMT mice. Additionally, exogenous immunoglobulins induced interleukin-6 and metalloproteinase-9 secretions in human AAA tissue cultures. Furthermore, administration of R788, a specific Syk inhibitor, suppressed AAA expansion, reduced inflammatory response, and reduced immunoglobulin deposition in AAA tissue. CONCLUSIONS: From these results, we concluded that B cells and immunoglobulins participated in AAA pathogenesis by promoting inflammatory and tissue-destructive activities. Finally, we identified Syk as a potential therapeutic target.

Endovascular Stent-Graft Repair of a Persistent Sciatic Artery Aneurysm.

Persistent sciatic artery (PSA) is a rare anomaly that may cause various symptoms, such as aneurysm, rupture, thromboembolism, and sciatica. Direct surgery can be performed to treat PSA aneurysm (PSAA), but is associated with complications; e.g., anatomical problems such as sciatic nerve injury. Herein we report a case of a 74-year-old woman with acute limb ischemia that developed from a distal embolism caused by a thrombus in the left PSAA; favorable results were obtained for her by treatment with a stent-graft after rapid anticoagulation therapy for limb salvage.

D-dimer value more than 3.6 µg/ml is highly possible existence deep vein thrombosis.

OBJECTIVE: The present study aimed to establish whether a more optimal cutoff value for D-dimer testing could definitively rule out acute deep vein thrombosis (DVT). METHODS: Between April 2009 and March 2010, 190 referral patients suspected to have DVT were assessed by the D-dimer assay. Additionally, ultrasonography (US) and computed tomography (CT) imaging were performed to detect thrombosis. RESULTS: DVT was identified in 47 patients (24%). The average D-dimer level in patients with DVT was 17.6±22.4 µg/ml, and was significantly lower (p=0.035),] at 2.7±4.2 µg/ml, in those without DVT. On the basis of receiver operating curve analysis, the specificity of the D-dimer for diagnosing DVT increased from 40% to 78.3%, and its sensitivity reached 93.8%, when the cutoff value for the assay was set at 3.6 µg/ml. CONCLUSIONS: D-dimer value over 3.6 µg/ml was highly prognostic for DVT.

Thoracic endovascular aortic repair with homemade stent grafts: early and mid-term outcomes.

PURPOSE: We reviewed our experience with homemade stent grafts in the repair of a variety of thoracic aortic lesions. The objective of this study was to assess the early and mid-term outcomes of this therapy. METHODS: From 1999 to 2007, homemade stent grafts were inserted in 88 patients with an atherosclerotic aneurysm, dissection, pseudoaneurysm, trauma, or rupture in the thoracic aorta. The endoprostheses were stainless steel Z-stents covered by a polyester graft, and were custom-designed for each patient. RESULTS: Placement of stent grafts was technically successful in 81 of the 88 patients (92%). Within 30 days after treatment, 3 patients died, 3 had a cerebral infarction, and 3 had onset of paraplegia or paraparesis. Primary endoleaks were observed in 8 patients (9%). During the mean follow-up period of 32 ± 26 months, 7 patients had persistent endoleaks and 7 had stent-graft migration. The aneurysm-related mortality rate was 7%. The rate of freedom from open-surgery conversion at 32 months was 89.0%. CONCLUSIONS: Our early experience with elective and emergency thoracic endovascular aortic repair using homemade stent grafts provided therapeutic benefits to high-risk patients. Endoleaks and stent-graft migrations were the factors most commonly responsible for secondary intervention in the mid-term period. Careful follow-up of patients treated with this approach is needed to avoid major complications in the long term.

A case of angioleiomyoma presenting as a pulsatile tumor in the left ring finger.

Angioleiomyomas in the finger are rare and their preoperative diagnosis is difficult. Most of them are not associated with arteries and their chief complaint does not reveal pulsation tumor. We report a case of the angioleiomyoma in the finger which was misdiagnosed as arteriovenous fistula of tumor, based on the presence of pulsating tumor and angiography finding.

Hepatocyte growth factor promotes an anti-inflammatory cytokine profile in human abdominal aortic aneurysm tissue.

Abdominal aortic aneurysm (AAA) is characterized by the destruction of tissue architecture due to chronic inflammation of unknown etiology. Recent studies have indicated that control of inflammation is a promising therapeutic strategy; however, no established pharmacological intervention is currently available for AAA. We found that hepatocyte growth factor (HGF) was expressed in aneurysmal tissue, and colocalized with von Willebrand factor, the endothelial cell marker, in the most damaged part of the aneurysmal walls. In ex vivo cultures of human AAA tissue, exogenously added HGF in the presence of tumor necrosis factor-alpha (TNF-α) enhanced the secretion of anti-inflammatory cytokine interleukin-10 (IL-10) and suppressed the secretion of proinflammatory monocyte/macrophage chemotactic protein-1 (MCP-1). The angiotensin converting enzyme (ACE) inhibitors, imidaprilat and perindoprilat, enhanced the secretion of endogenous HGF, augmented the TNF-α-induced IL-10 secretion and suppressed MCP-1 secretion from AAA tissue. The ACE inhibitors also augmented the expression of HGF in the presence of bradykinin in human aortic endothelial cells in culture (HAECs). In contrast, HGF secretion was not affected by either an angiotensin II type 1 receptor (AT1) antagonist or angiotensin II in AAA tissue or in HAECs. These results suggested that angiotensin converting enzyme inhibitors may be useful in controlling chronic inflammation in AAA, partly due to their enhancement of HGF secretion.

[Long-term outcomes of thoracic endovascular aortic repair with homemade stent-grafts].

We reviewed our experience with homemade stent-grafts in the repair of thoracic aortic lesions. The objective of this study was to assess the long-term outcomes of this therapy. From 1999 to 2008, homemade stent-grafts were inserted in 94 patients with various thoracic diseases. The endoprostheses were stainless steel Z-stents covered with polyester graft and were custom designed for each patient. Placement of the stent-grafts was technically successful in 85 of the 94 patients (90%). Within 30 days after the treatment, 4 patients died, 3 had cerebral infarction, and 3 had the onset of paraplegia or paraparesis. Primary endoleaks were observed in 10 patients (11%). During the mean follow-up period of 43 +/- 29 months, 10 patients had endoleaks and 8 had stent-graft migration. The aneurysm-related mortality rate was 12%. Our early outcomes of elective and emergency thoracic endovascular aortic repair with homemade stent-grafts demonstrated their therapeutic effectiveness in high-risk patients with various thoracic diseases. Endoleaks and migration were, however, the factors most responsible for secondary intervention in the mid-term period. Careful follow-up of the treated patients is needed to avoid the major complication in the long-term period.

Non-permanent inferior vena cava filters for prophylaxis and treatment of lower limb venous thromboembolism.

OBJECTIVES: The purpose of this study was to evaluate and compare our recent clinical experience with temporary inferior vena cava (IVC) filters (TF) and retrievable IVC filters (RF). MATERIALS AND METHODS: Patients who received TF or RF implantation between October 2002 and May 2009 were studied. The early clinical outcomes between the 2 groups were compared. RESULTS: Nonpermanent IVC filters were placed in 119 patients (34 in TF and 85 in RF). Retrieval of RF and removal of TF were successful in 98.7% and 100%, respectively. The incidence of filter-related complications for TF was significantly higher than for RF (26.5% vs 3.5%; P = .0004). However, no symptomatic pulmonary embolism (PE) was observed during filter placement. CONCLUSION: TF and RF provided similar protection from PE. We prefer RF because they can be left in permanently if it is impossible to remove or retrieve the filter for some reason.