Good Collateral Formation Research Articles

Effect of Fibroblast Growth Factor-21 Molecule on Coronary CollateralDevelopment.

Collateral arteries provide an alternative source to the myocardium resulting from ischemia due to occlusive coronary artery disease and may help preserve myocardial function in the case of coronary artery disease (CAD). Although collateral development is so important, its pathophysiology has not been fully elucidated. Till now, no study has investigated the relationship between Fibroblast growth factor-21(FGF-21) and coronary collateral. This study aims to investigate the pathophysiology of coronary collateral development. In our study, which we planned as a case-control, 60 consecutive patients with ≥90 stenosis in at least one large coronary artery as a result of coronary angiography (CAG) and 30 patients with normal coronary angiography were included in the study cross-sectional. Demographic, echocardiographic and laboratory data were recorded. Coronary collateral circulation was evaluated using the Rentrop-Cohen method. FGF-21 levels were measured in all individuals. In the analysis, no significant difference was observed between the two groups in basic biochemical parameters other than HDL (p>0.05 for all). FGF-21 level was statistically significantly higher in the patient group compared to the control group (p: 0.003). Also, the FGF-21 level was found to be statistically significantly higher in the good collateral circulation group than the poor (p:0.006). Univariate and multivariate logistic regression analysis was performed to predict the presence of collateral. We found that FGF-21(p=0.006), and C-reactive protein (p=0.020) predicted the presence of collateral independently. Collateral formation and cardiac prognosis are closely related. Our study is the first to investigate the relationship between collateral formation and FGF-21. Our study showed that the FGF-21 level is an independent predictor of collateral formation. In addition, there was a significant difference between bad and good collateral formation regarding FGF-21 levels.

Assessment of plasma soluble Tie-2 level to distinguish moyamoya disease from atherosclerotic cerebrovascular disease and predict postoperative neovascularization.

Moyamoya disease (MMD) is a chronic steno-occlusive cerebrovascular disease and features the formation of hazy collateral vessels at the base of the brain. Angiopoietin (Ang)-1 and -2, their receptor Tie-2, and vascular endothelial growth factor (VEGF) that regulate angiogenesis might be important in MMD pathophysiology and postoperative collateral formation. The goal of this study was to determine whether levels of these angiogenic factors could predict collateralization in patients with MMD. A total of 196 patients with MMD and 57 with atherosclerotic cerebrovascular disease serving as controls were enrolled. Ang-1, Ang-2, Tie-2, and VEGF mRNA levels were analyzed in middle cerebral artery (MCA) arterial wall specimens by using real-time quantitative polymerase chain reaction. MCA and peripheral plasma concentrations of Ang-1, Ang-2, soluble Tie-2 (sTie-2), and VEGF were examined by enzyme-linked immunosorbent assay. Cerebral arteriography was performed 6 months after bypass surgery to assess the postoperative collateralization. In MCA specimens, patients with MMD exhibited higher expression levels of Ang-1 and Ang-2 but lowered VEGF expression. The patients with MMD had significantly higher concentrations of Ang-1 and Ang-2 but lower levels of VEGF in MCA plasma. Peripheral plasma concentrations of these growth factors were not changed. MCA and peripheral plasma sTie-2 levels were both reduced in patients with MMD. The 6-month follow-up showed that patients with good collateral formation had lower sTie-2 levels in both MCA and peripheral plasma. Furthermore, the Suzuki stage and peripheral plasma sTie-2 level were significantly correlated with good postoperative collateral formation on multivariate analysis. Ang-1, Ang-2, Tie-2, and VEGF are involved in MMD pathogenesis. The peripheral plasma level of sTie-2 can differentiate MMD from atherosclerotic cerebrovascular disease and serve as a novel biomarker to predict postoperative collateral formation.

The Value of Preoperative Phase-Contrast MRI in Predicting the Clinical Outcome of Moyamoya Disease after Encephalo-Duro-Arterial Synangiosis Surgery.

In patients with Moyamoya disease, the relationship between preoperative hemodynamic status and prognosis after encephalo-duro-arterial synangiosis (EDAS) surgery was unclear. We aimed to explore the value of the preoperative hemodynamic status acquired by cine phase-contrast MR imaging in predicting collateral formation and clinical outcomes after EDAS surgery in patients with Moyamoya disease. Participants with Moyamoya disease were prospectively recruited and underwent preoperative phase-contrast MR imaging. All participants were classified into good and poor groups according to the collateral formation after EDAS surgery. On the basis of the change in the mRS system, participants were classified into the improved mRS group and the poor response group. Hemodynamic status including mean velocity, peak velocity, and blood volume flow of the superficial temporal artery was compared between groups. Logistic regression was performed to relate the phase-contrast MR imaging parameters to collateral formation and clinical outcomes. A total of 45 patients with Moyamoya disease with unilateral EDAS surgery were finally included. Mean velocity, peak velocity, and blood volume flow of the ipsilateral superficial temporal artery were significantly greater in patients with good collateral formation compared with those with poor collateral formation (P = .011, .004, and .013, respectively). The mean velocity, peak velocity, and blood volume flow were independently associated with postoperative collateral formation after adjusting for confounding factors. Furthermore, the peak velocity of the ipsilateral superficial temporal artery was also significantly associated with improvement of the mRS score. Good hemodynamic status of the ipsilateral superficial temporal artery as a donor artery evaluated by phase-contrast MR imaging was significantly associated with better collateral formation and improved mRS after EDAS surgery in patients with Moyamoya disease.

A Proposed Algorithm for Managing Cerebral Proliferative Angiopathy

Cerebral proliferative angiopathy (CPA) is a rare disease, characterized by a large vascular nidus, diffuse angiogenesis, and intermingled normal brain tissue. Conservative treatment, endovascular intervention, indirect revascularization, and radiotherapy have been applied to treat this disease. However, some cases deteriorate even after non-conservative treatment, and there has been no standard of treatment for this disease so far. In order to build a better treatment strategy, we review literature, present our case and propose an algorithm for managing CPA. Following the PRISMA principle, we systemically reviewed literature discussing CPA. A case successfully managed with multi-modal treatment is also illustrated. A total of 23 articles with 74 cases of CPA were found. Thirty-three patients received single-modal management. These 33 cases include 24 receiving endovascular intervention, 7 receiving indirect revascularization, and 2 receiving radiotherapy. Three of the 33 patients deteriorated clinically, and 1 expired. We present a 6-year-old boy with left hemispheric CPA receiving indirect revascularization, followed by 2 consecutive courses of stereotactic radiosurgery targeting arteriovenous shunts in the left basal ganglia and arteriovenous shunts around the olfactory groove. In the follow-up period of more than 4years, good collateral formation, improved perilesional perfusion, CPA shrinkage, and symptom relief were all achieved. Based on our literature review and case, we propose an algorithm for the management of CPA and emphasize that multi-modal treatment is necessary for most CPA cases.

Impact of serum erythropoietin level on collateral vessel development in patients with coronary artery disease.

Objective:Experimental data have shown that Erythropoietin (EPO) stimulates angiogenesis and neovascularization which may result in improved collateral development. The aim of this study was to investigate the association between serum EPO levels and the extent of coronary collaterals. Patient characteristics possibly related with coronary collaterals were also sought.Methods:A total of 256 patients with high grade coronary stenosis or occlusion were evaluated for the extent of coronary collaterals using Rentrop classification. Patients with grade 0 or 1 collaterals were grouped as poor collaterals, while grade 2 or 3 collaterals were grouped as good collaterals.Results:Mean age of the study population was 63 years, 77% were males. Subjects with good collaterals were significantly more likely to have anemia (p=0.038) and stable angina pectoris as clinical presentation (p=0.40). Serum EPO levels were not different among good and poor colla- teral groups (10.4±9.4 mU/mL vs. 9.7±11 mU/mL, p=0.397). The prevalence of all other cardiovascular risk factors, medications, and angiographic characteristics were similar between the two groups. After adjusting for age, gender, and clinical presentation with stable angina pectoris, pre- sence of anemia persisted to be a significant correlate of the good collateral formation (OR: 1.95; 95%; CI: 1.07–3.54, p=0.029).Conclusion:There has been conflicting results from trials studying the effects of serum EPO on coronary collateral development. The present study, with the largest patient population studying this topic, suggests that presence of anemia, but not serum EPO level, is associated with good collateral development.

Expression of circulating vascular endothelial growth factor-antagonizing cytokines and vascular stabilizing factors prior to and following bypass surgery in patients with moyamoya disease.

The aim of the present study was to investigate the levels of vascular endothelial growth factor (VEGF)-antagonizing cytokines and VEGF-influenced vascular stabilizing cytokines in patients with moyamoya disease (MMD) and the association with postoperative collateral vessel formation. The study population included 53 MMD patients that had undergone indirect bypass surgery and 50 healthy controls. Serum levels of VEGF, thrombospondin-1 (TSP-1), TSP-2, soluble VEGF receptor-1 (sVEGFR-1), sVEGFR-2, endostatin, angiopoietin-1 (Ang-1) and Ang-2 were measured at the baseline (preoperative) and at day seven following surgery. Postoperative collateralization assessment was conducted upon the six-month follow-up cerebral angiography. Cytokine levels were compared between patients with good or poor collateral formation. Compared with the healthy controls, MMD patients exhibited lower baseline levels of sVEGFR-1 (P<0.0001) and sVEGFR-2 (P<0.0001), but higher VEGF expression (P<0.0001). Ang-1 and Ang-2 levels did not exhibit any difference between the two groups. On day seven following surgery, MMD patients exhibited an almost unchanged sVEGFR-1 and sVEGFR-2 expression level, but upregulated expression of VEGF (P<0.0001), Ang-1 (P<0.0001) and TSP-2 (P<0.0001). The six-month follow-up angiographies revealed that 21 patients (45.65%) that had undergone the same surgical procedure achieved good collateralization. Patients with good collateral formation appeared to have lower sVEGFR-1 and sVEGFR-2 levels prior to (P=0.029 and P=0.045, respectively) and at day seven (P=0.044 and P=0.047, respectively) following bypass surgery when compared with the patients with worse collateralization. Therefore, sVEGFR-1 and sVEGFR-2 may play a role in the pathogenesis of MMD. Lower levels of sVEGFR-1 and sVEGFR-2 indicated better postoperative collateralization in the six months following indirect bypass surgery. However, Ang-1 and Ang-2 may not be specifically involved in the course of MMD.

Treatment of moyamoya disease in the adult population with pial synangiosis

Surgical treatment of moyamoya disease in the adult population commonly uses direct revascularization, the superficial temporal artery (STA) to middle cerebral artery (MCA) bypass (STA-MCA). Pial synangiosis, a method of indirect revascularization, has been used in adult patients with moyamoya when STA-MCA bypass was not technically feasible. Although the effectiveness of pial synangiosis has been well described in children, only limited reports have examined its role in adult patients with moyamoya disease. In this study the authors report on their experience with pial synangiosis revascularization for this population. The authors reviewed the clinical and radiographic records of all adult patients (≥ 18 years of age) with moyamoya disease who underwent cerebral revascularization surgery using pial synangiosis at a single institution. From 1985 to 2010, 66 procedures (6 unilateral, 30 bilateral) were performed on 36 adult patients with moyamoya disease. The mean age at surgery was 28.3 years, and 30 patients were female. Twenty-eight patients (77.8%) presented with transient ischemic attacks (TIAs), 24 (66.7%) with stroke, and 3 (8.3%) with hemorrhage. Preoperative Suzuki stage was III or higher in 50 hemispheres (75.8%) and 3 patients had undergone prior treatments to the affected hemisphere before pial synangiosis surgery. Clinical follow-up was available for an average of 5.8 years (range 0.6-14.1 years), with 26 patients (72.2%) followed for longer than 2 years. Postoperative angiography was available for 24 patients and 46 revascularized hemispheres, and 39 (84.8%) of the 46 hemispheres demonstrated good collateral formation (Matsushima Grade A or B). Postoperative complications included 3 strokes, 5 TIAs, and 2 seizures, and there was no hemorrhage during the follow-up period. One patient required additional revascularization surgery 8 months after pial synangiosis. Pial synangiosis is a safe and durable method of cerebral revascularization in adult patients with moyamoya and can be considered as a potential treatment option for moyamoya disease in adults.

Predictor of Poor Coronary Collaterals in Elderly Population With Significant Coronary Artery Disease

BackgroundCoronary collateral circulation plays an important role in protecting myocardium from ischemia and reducing cardiovascular events. Advanced age might be associated with poor coronary collateral development and cardiovascular outcome. However, limited studies investigate the predictors for collateral development in the elderly population. MethodsThe authors evaluated 950 consecutive patients undergoing coronary angiography and finally analyzed 207 patients of 65 years or more. The collateral scoring system developed by Rentrop was used to classify patients into those with poor or good collateral formation. ResultsThe patients with poor collateral were older age, had lower incidence of smoking, more male sex, had fewer diseased vessels and had a trend to be diabetic. Multivariate analysis showed age (odds ratio (OR)=1.068; P=0.019), diabetes (OR=2.681; P=0.003) and diseased vessels numbers (OR=0.337; P<0.001) were significant predictors of poor collaterals development. Furthermore, age and diabetes have a synergistic effect on poor collateral development (P=0.041 for interaction). ConclusionsEven in the elderly population, age and diabetes might negatively influence the coronary collaterals development.

Abstract TP149: Moyamoya Disease in Pregnancy: Protective Effect of Cerebral Revascularization via Pial Synangiosis

Introduction: Pregnancy, labor and delivery may lead to hemodynamic changes that could cause neurologic complications in patients with moyamoya disease (MMD). We reviewed an operative series of moyamoya patients treated by pial synangiosis from 1985 to 2012 to identify those patients who became pregnant in an attempt to determine the safety of pregnancy in this group of patients. Methods: Clinical and radiographic records of all adult moyamoya patients treated at a single institution from 1985 to 2012 were retrospectively reviewed. Results: From 1985-2012, 8 pial synangiosis surgeries were performed on 5 women with moyamoya disease before or during pregnancy. The mean age at surgery was 16.2. Four patients presented with stroke and one with transient ischemic attacks. Pre-operative Suzuki grade was III or higher in all treated hemispheres. Post-operative angiogram was available in 3 patients (5 treated hemispheres), and all demonstrated good collateral formation (Matsushima grade A or B). Clinical follow-up was available for an average of 13.0 years (range 1-22.0 years). The mean duration from surgery to delivery was 9.4 years; one patient was diagnosed with MMD during pregnancy and was operated at 4 months gestation. All women experienced successful pregnancy outcome: three had normal vaginal delivery and two underwent Caesarean section. Post-pregnancy stroke occurred on the contralateral hemisphere in one patient originally treated with unilateral moyamoya. This patient was found to have developed MMD on the other hemisphere and underwent additional revascularization. No other complications were observed during the follow-up period. Conclusions: Women with moyamoya disease can go through pregnancy safely and successfully after adequate cerebral revascularization.

Abstract TMP42: Treatment of Moyamoya Disease in the Adult Population with Pial Synangiosis

Introduction: Surgical treatment of moyamoya disease in the adult population commonly employs direct revascularization, the superficial temporal artery to middle cerebral artery (STA-MCA) bypass. Pial synangiosis, a method of indirect revascularization, has been utilized in adult moyamoya patients when STA-MCA bypass is not technically feasible. Although the effectiveness of pial synangiosis has been well described in children, only limited reports have examined its role in adult moyamoya patients. Here we report on our experience with pial synangiosis revascularization for this population. Methods: We reviewed the clinical and radiographic records of all adult moyamoya patients (18 years of age or older), who underwent cerebral revascularization surgery using pial synangiosis at a single institution. Results: From 1985-2010, 66 procedures (6 unilateral, 30 bilateral) were performed on 36 adult moyamoya patients. The mean age at surgery was 28.3 (range: 19 - 51) and 30 were female. Thirty-one patients (86.1%) presented with either stroke or TIA and 3 (8.3%) with hemorrhage. Pre-operative Suzuki grade was III or higher in 50 hemispheres (75.7%) and 3 patients had prior treatments to the affected hemisphere before pial synangiosis surgery. Clinical follow-up was available for an average of 5.8 years (range 0.6-14.1 years), with 26 (72.2%) patients followed for longer than 2 years. Post-operative angiogram was available for 24 patients and 46 revascularized hemispheres, and 39 (84.8%) demonstrated good collateral formation (Matsushima grade A or B). Peri-operative complications included 3 strokes, 5 TIA’s, and 2 seizures, and there was no stroke or hemorrhage during the follow-up period. One patient required additional revascularization surgery 8 months after pial synangiosis. Conclusions: Pial synangiosis is a safe, effective, and durable method of cerebral revascularization in adult moyamoya patients. Our data supports the utilization of pial synangiosis as a treatment option for moyamoya disease in adults, particularly when STA-MCA bypass is not technically feasible.

The Relationship between Plasma Homocysteine and Early Coronary Collateral Vessel Development after Acute Myocardial Infarction

Aim: Homocysteine is known to inhibit endothelial cell proliferation, which is a key event in angiogenesis. Factors responsible for the presence or absence of coronary collateral circulation are poorly understood. Therefore, in this study we investigated the effect of plasma homocysteine level on the early formation of angiographically visible collaterals after acute myocardial infarction. Materials and Methods: The study included 60 patients that had ST-segment elevation myocardial infarction (STEMI). All the patients underwent coronary angiography 1-4 days after admission (mean: 2.3 ± 1.2 days). Patients were graded according to Rentrop classification. Patients with grade 0 or 1 collateral vessels were classified as poor collaterals; patients with grade 2 or 3 collateral vessels were classified as good collaterals. Results: In all, 35 (58.3%) patients had poor collateral vessel filling and the remaining 25 (41.7%) patients had good collateral filling. Plasma homocysteine concentration in patients with poor and good collateral formation was 18.2 ± 8.6 µmol/l and 12.7 ± 2.4 µmol/l, respectively (P = 0.008). There was a negative linear correlation between Rentrop subclasses and plasma homocysteine concentration (r = –0.391, P = 0.002). We assessed the effect of demographic variables, such as age, gender, hypertension, diabetes mellitus, smoking, lipid parameters, and plasma homocysteine concentration, on the development of collaterals. The only independent variable that affected the development of collaterals was homocysteine level (OR: 0.71; 95% CI = 0.57-0.89, P = 0.003). Conclusions: This study demonstrates for the first time that there is an inverse relationship between the early development of collateral circulation after acute myocardial infarction and plasma homocysteine concentration.

Intermittent claudication secondary to a traumatic arteriovenous fistula

Arteriovenous fistula (AVF) formation is a recognized complication of arterial trauma. A 63-year-old man with no known risk factors for atheroma and a history of a 20-year delay in the diagnosis and treatment of a traumatic AVF presented with right calf claudication (maximal walking distance = 150 m). A duplex ultrasound scan and a magnetic resonance angiography showed an aneurysmatic dilatation and partial thrombosis of the infrarenal aorta and the right leg feeding arteries. Selective angiography revealed a complete occlusion of the right popliteal artery in the segment 2 and the infrapopliteal arteries with good collateral formation in the lower leg. At this time, there is no indication for infragenual arterial revascularisation in this patient. Instead, therapy consists of exercise training and antiplatelet therapy. We concluded, that peripheral microembolism from the aneurysmatic aorta, iliac or femoral arteries is most probably the reason for the popliteal occlusion in this patient, representing a rare, nonatherosclerotic cause of claudication.

Revascularisation surgery for paediatric moyamoya: a review of the literature

The role of and optimal surgical revascularisation technique for paediatric moyamoya syndrome (MMS) are controversial. In this literature review our primary aim was to evaluate the evidence base for the efficacy of surgical revascularisation for the treatment of paediatric MMS. Secondary aims were to estimate the rate of peri-operative complications and to ascertain whether direct or indirect revascularisation techniques resulted in differences in clinical or radiological outcomes. Papers describing surgical revascularisation and its outcome in the treatment of children with MMS were identified from the OVID Medline database (1966-2004). Only papers in English were reviewed. Data were abstracted using a standardised form. Fifty-seven studies, including data on 1,448 patients, were reviewed. Most were Japanese; 10% were from Western institutions. Indications for revascularisation were described in <15% of studies and varied between centres. Indirect procedures were most commonly performed (alone in 73% of cases, combined with direct procedures in 23%). The rates of peri-operative stroke and reversible ischaemic events were 4.4 and 6.1% respectively. Out of 1,156 (87%) patients, 1,003 derived symptomatic benefit from surgical revascularisation (complete disappearance or reduction in symptomatic cerebral ischaemia), with no significant difference between the indirect and direct/combined groups. Data on developmental and functional outcomes were limited and of uncertain significance as they were not related to pre-operative status. Good collateral formation was significantly more frequent in the direct/combined group than in the indirect group (chi(2), p<0.001). Data from the medical literature suggest that surgical revascularisation is a safe intervention for paediatric MMS and most treated patients derive some symptomatic benefit. However, paucity of data on selection criteria and more global outcome measures means that the impact of surgical revascularisation on natural history remains uncertain. Direct and/or combined procedures provide better revascularisation, but this is not associated with differences in symptomatic outcome. International standardisation of the clinical approach to the treatment of paediatric MMS is urgently needed to critically evaluate the optimal indications for and timing of surgical revascularisation.

A case of adult moyamoya disease showing progressive angiopathy on cerebral angiography

In moyamoya disease, progression of carotid occlusive lesion in an adult patient is very rare. We report a case of adult moyamoya disease with acute angiographical stage progression and hemodynamic deterioration. A 56-year-old female complaining of left motor weakness visited our department. On MRI, infarct lesion was found in the right white matter. On cerebral angiography, occlusive lesions in the bilateral internal carotid arterial siphons and moyamoya vessels were found. The right side was stage V and the left side was stage III. On IMP-SPECT, decreased cerebral hemodynamic reserve of the right cerebral hemisphere was found. In this patient, right STA-MCA anastomosis was performed. After operation, she became possible to walk and discharged to home. Five months after operation, good collateral formation and improvement of hemodynamic reserve in the right hemisphere were found. However, on left carotid arteriography, the anterior and middle cerebral arteries were only slightly imaged, and the disease state progressed to stage IV. In addition, decreased blood flow and hemodynamic reserve were appeared in the left hemisphere.