Levosimendan in patients with ischaemic heart disease

Levosimendan is a drug developed for the treatment of heart failure. Its mechanism of action includes calcium sensitization of contractile proteins and the opening of ATP-sensitive potassium channels. The combination of positive inotropy with possible anti-ischaemic effects via potassium channel opening may offer benefits in comparison with currently available intravenous inotropes, which are contraindicated in patients with ongoing myocardial ischaemia. The active levosimendan metabolite OR-1896 significantly prolongs the duration of the haemodynamic effects of levosimendan. The aims of the present study were to investigate: 1) the clinical effects and safety of intravenous and oral levosimendan and 2) the pharmacodynamics and pharmacokinetics of intravenous and oral levosimendan and its metabolites in patients with ischaemic heart disease. Levosimendan was administered intravenously or orally in four studies to 557 patients with ischaemic heart disease with or without concomitant heart failure. One study included patients with acute myocardial infarction, while the other three studies included stable ischaemic patients. Non-invasive haemodynamic measurements were used in all studies, and blood samples for pharmacokinetics were drawn in three studies. Safety was followed by ECG recordings, adverse event inquiries and laboratory assessments. Intravenous levosimendan, administered as a 6-hour infusion did not cause clinically significant hypotension or ischaemia in comparison with placebo and reduced worsening heart failure and short- and long-term mortality. Increase in incidence of hypotension and ischaemia was seen only with the highest dose (0.4 µg/kg/min). Both intravenous and oral levosimendan possessed a moderate positive inotropic effect. Vasodilatory effect was more pronounced with intravenous levosimendan. A chronotropic effect was seen in all studies; however, it was not accompanied by any increase in arrhythmic events. The formation of levosimendan metabolites after oral dosing increased linearly with the daily dose of the parent drug, leading to increased inotropic and chronotropic response. Levosimendan was well tolerated in all studies. In conclusion, levosimendan was safe and effective in the treatment of patients with acute or chronic ischaemia. The risk-benefit ratio of intravenous levosimendan is favourable up to the dose of 0.2 µg/kg/min. The daily dose of oral levosimendan in patients with ischaemic heart failure should not exceed 4 mg due to an increase in chronotropic response.

Determinants of vascular cognitive impairment : White matter lesions, brain atrophy and their neuropsychological correlates

The concept of vascular cognitive impairment (VCI) covers a wide spectrum of cognitive dysfunctions related to cerebrovascular disease. Among the pathophysiological determinants of VCI are cerebral stroke, white matter lesions and brain atrophy, which are known to be important risk factors for dementia. However, the specific mechanisms behind the brain abnormalities and cognitive decline are still poorly understood. The present study investigated the neuropsychological correlates of particular magnetic resonance imaging (MRI) findings, namely, medial temporal lobe atrophy (MTA), white matter hyperintensities (WMH), general cortical atrophy and corpus callosum (CC) atrophy in subjects with cerebrovascular disease. Furthermore, the cognitive profile of subcortical ischaemic vascular disease (SIVD) was examined. This study was conducted as part of two large multidisciplinary study projects, the Helsinki Stroke Aging Memory (SAM) Study and the multinational Leukoaraiosis and Disability (LADIS) Study. The SAM cohort consisted of 486 patients, between 55 and 85 years old, with ischaemic stroke from the Helsinki University Hospital, Helsinki, Finland. The LADIS Study included a mixed sample of subjects (n=639) with age-related WMH, between 65 and 84 years old, gathered from 11 centres around Europe. Both studies included comprehensive clinical and neuropsychological assessments and detailed brain MRI. The relationships between the MRI findings and the neuropsychological test performance were analysed by controlling for relevant confounding factors such as age, education and other coexisting brain lesions. The results revealed that in elderly patients with ischaemic stroke, moderate to severe MTA was specifically related to impairment of memory and visuospatial functions, but mild MTA had no clinical relevance. Instead, WMH were primarily associated with executive deficits and mental slowing. These deficits mediated the relationship between WMH and other, secondary cognitive deficits. Cognitive decline was best predicted by the overall degree of WMH, whereas the independent contribution of regional WMH measures was low. Executive deficits were the most prominent cognitive characteristic in SIVD. Compared to other stroke patients, the patients with SIVD also presented more severe memory deficits, which were related to MTA. The cognitive decline in SIVD occurred independently of depressive symptoms and, relative to healthy control subjects, it was substantial in severity. In stroke patients, general cortical atrophy also turned out to be a strong predictor of cognitive decline in a wide range of cognitive domains. Moreover, in elderly subjects with WMH, overall CC atrophy was related to reduction in mental speed, while anterior CC atrophy was independently associated with frontal lobe-mediated executive functions and attention. The present study provides cross-sectional evidence for the involvement of WMH, MTA, general cortical atrophy and CC atrophy in VCI. The results suggest that there are multifaceted pathophysiological mechanisms behind VCI in the elderly, including both vascular ischaemic lesions and neurodegenerative changes. The different pathological changes are highly interrelated processes and together they may produce cumulative effects on cognitive decline.

Depression and its assessment among stroke patients and their caregivers

Approximately one-third of stroke patients experience depression. Stroke also has a profound effect on the lives of caregivers of stroke survivors. However, depression in this latter population has received little attention. In this study the objectives were to determine which factors are associated with and can be used to predict depression at different points in time after stroke; to compare different depression assessment methods among stroke patients; and to determine the prevalence, course and associated factors of depression among the caregivers of stroke patients. A total of 100 consecutive hospital-admitted patients no older than 70 years of age were followed for 18 months after having their first ischaemic stroke. Depression was assessed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R), Beck Depression Inventory (BDI), Hamilton Rating Scale (HRSD), Visual Analogue Mood Scale (VAMS), Clinical Global Impression (CGI) and caregiver ratings. Neurological assessments and a comprehensive neuropsychological test battery were performed. Depression in caregivers was assessed by BDI. Depressive symptoms had early onsets in most cases. Mild depressive symptoms were often persistent with little change during the 18-month follow-up, although there was an increase in major depression over the same time interval. Stroke severity was associated with depression especially from 6 to 12 months post-stroke. At the acute phase, older patients were at higher risk of depression, and a higher proportion of men were depressed at 18 months post-stroke. Of the various depression assessment methods, none stood clearly apart from the others. The feasibility of each did not differ greatly, but prevalence rates differed widely according to the different criteria. When compared against DSM-III-R criteria, sensitivity and specificity were acceptable for the CGI, BDI, and HRSD. The CGI and BDI had better sensitivity than the more specific HRSD. The VAMS seemed not to be a reliable method for assessing depression among stroke patients. The caregivers often rated patients depression as more severe than did the patients themselves. Moreover, their ratings seemed to be influenced by their own depression. Of the caregivers, 30-33% were depressed. At the acute phase, caregiver depression was associated with the severity of the stroke and the older age of the patient. The best predictor of caregiver depression at later follow-up was caregiver depression at the acute phase. The results suggest that depression should be assessed during the early post-stroke period and that the follow-up of those at risk of poor emotional outcome should be extended beyond the first year post-stroke. Further, the assessment of well-being of the caregivers of stroke patients should be included as a part of a rehabilitation plan for stroke patients.

Determinants of Coronary and Carotid Atherosclerosis in Finnish Patients with Clinically Suspected Coronary Artery Disease. A Quantitative Angiography and Ultrasound Study

Background. Cardiovascular disease (CVD) remains the most serious threat to life and health in industrialized countries. Atherosclerosis is the main underlying pathology associated with CVD, in particular coronary artery disease (CAD), ischaemic stroke, and peripheral arterial disease. Risk factors play an important role in initiating and accelerating the complex process of atherosclerosis. Most studies of risk factors have focused on the presence or absence of clinically defined CVD. Less is known about the determinants of the severity and extent of atherosclerosis in symptomatic patients. Aims. To clarify the association between coronary and carotid artery atherosclerosis, and to study the determinants associated with these abnormalities with special regard to novel cardiovascular risk factors. Subjects and methods. Quantitative coronary angiography (QCA) and B-mode ultrasound were used to assess coronary and carotid artery atherosclerosis in 108 patients with clinically suspected CAD referred for elective coronary angiography. To evaluate anatomic severity and extent of CAD, several QCA parameters were incorporated into indexes. These measurements reflected CAD severity, extent, and overall atheroma burden and were calculated for the entire coronary tree and separately for different coronary segments (i.e., left main, proximal, mid, and distal segments). Maximum and mean intima-media thickness (IMT) values of carotid arteries were measured and expressed as mean aggregate values. Furthermore, the study design included extensive fasting blood samples, oral glucose tolerance test, and an oral fat-load test to be performed in each participant. Results. Maximum and mean IMT values were significantly correlated with CAD severity, extent, and atheroma burden. There was heterogeneity in associations between IMT and CAD indexes according to anatomical location of CAD. Maximum and mean IMT values, respectively, were correlated with QCA indexes for mid and distal segments but not with the proximal segments of coronary vessels. The values of paraoxonase-1 (PON1) activity and concentration, respectively, were lower in subjects with significant CAD and there was a significant relationship between PON1 activity and concentration and coronary atherosclerosis assessed by QCA. PON1 activity was a significant determinant of severity of CAD independently of HDL cholesterol. Neither PON1 activity nor concentration was associated with carotid IMT. The concentration of triglycerides (TGs), triglyceride-rich lipoproteins (TRLs), oxidized LDL (oxLDL), and the cholesterol content of remnant lipoprotein particle (RLP-C) were significantly increased at 6 hours after intake of an oral fatty meal as compared with fasting values. The mean peak size of LDL remained unchanged 6 hours after the test meal. The correlations between total TGs, TRLs, and RLP-C in fasting and postprandial state were highly significant. RLP-C correlated with oxLDL both in fasting and in fed state and inversely with LDL size. In multivariate analysis oxLDL was a determinant of severity and extent of CAD. Neither total TGs, TRLs, oxLDL, nor LDL size were linked to carotid atherosclerosis. Insulin resistance (IR) was associated with an increased severity and extent of coronary atherosclerosis and seemed to be a stronger predictor of coronary atherosclerosis in the distal parts of the coronary tree than in the proximal and mid parts. In the multivariate analysis IR was a significant predictor of the severity of CAD. IR did not correlate with carotid IMT. Maximum and mean carotid IMT were higher in patients with the apoE4 phenotype compared with subjects with the apoE3 phenotype. Likewise, patients with the apoE4 phenotype had a more severe and extensive CAD than individuals with the apoE3 phenotype. Conclusions. 1) There is an association between carotid IMT and the severity and extent of CAD. Carotid IMT seems to be a weaker predictor of coronary atherosclerosis in the proximal parts of the coronary tree than in the mid and distal parts. 2) PON1 activity has an important role in the pathogenesis of coronary atherosclerosis. More importantly, the study illustrates how the protective role of HDL could be modulated by its components such that equivalent serum concentrations of HDL cholesterol may not equate with an equivalent, potential protective capacity. 3) RLP-C in the fasting state is a good marker of postprandial TRLs. Circulating oxLDL increases in CAD patients postprandially. The highly significant positive correlation between postprandial TRLs and postprandial oxLDL suggests that the postprandial state creates oxidative stress. Our findings emphasize the fundamental role of LDL oxidation in the development of atherosclerosis even after inclusion of conventional CAD risk factors. 4) Disturbances in glucose metabolism are crucial in the pathogenesis of coronary atherosclerosis. In fact, subjects with IR are comparable with diabetic subjects in terms of severity and extent of CAD. 5) ApoE polymorphism is involved in the susceptibility to both carotid and coronary atherosclerosis.

Adjuvant Arteriovenous Fistula for Infrapopliteal Bypass Patency

A lack of suitable venous graft material or poor outflow is an increasingly encountered situation in peripheral vascular surgery. Prosthetic grafts have clearly worse patency than vein grafts in femorodistal bypass surgery. The use of an adjuvant arteriovenous fistula (av-fistula) at the distal anastomosis has been postulated to improve the flow and thus increase prosthetic graft patency. In theory the adjuvant fistula might have the same effect in a compromised outflow venous bypass. A free flap transfer also augments graft flow and may have a positive effect on an ischaemic limb. The aim of this study was to evaluate the possible benefit of an adjuvant av-fistula and an internal av-fistula within a free flap transfer on the patency and outcome of an infrapopliteal bypass. The effect of the av-fistula on bypass haemodynamics was also assessed along with possible adverse effects. Patients and methods: 1. A prospective randomised multicentre trial comprised 59 patients with critical leg ischaemia and no suitable veins for grafting. Femorocrural polytetrafluoroethylene (PTFE) bypasses with a distal vein cuff, with or without an adjuvant av-fistula, were performed. The outcome was assessed according to graft patency and leg salvage. 2. Haemodynamic measurements were performed to a total of 50 patients from Study I with a prolonged follow-up. 3. Nine critically ischaemic limbs were treated with a modified radial forearm flap transfer in combination with a femorodistal bypass operation. An internal av-fistula was created within the free flap transfer to increase flap artery and bypass graft flow. 4. The effect of a previous free flap transfer on bypass haemodynamics was studied in a case report. 5. In a retrospective multicentre case-control study, 77 infrapopliteal vein bypasses with an adjuvant av-fistula were compared with matched controls without a fistula. The outcome and haemodynamics of the bypasses were recorded. Main results: 1. The groups with and without the av-fistula did not differ as regards prosthetic graft patency or leg salvage. 2. The intra- and postoperative prosthetic graft flow was significantly increased in the patients with the av-fistula. However, this increase did not improve patency. There was no difference in patency between the groups, even in the extended follow-up. 3. The vein graft flow increased significantly after the anastomosis of the radial forearm flap with an internal av-fistula. 4. A previously performed free flap transfer significantly augmented the flow of a poor outflow femoropedal bypass graft. 5. The adjuvant av-fistula increased the venous infrapopliteal bypass flow significantly. The increased flow did not, however, lead to improved graft patency or leg salvage. Conclusion: An adjuvant av-fistula does not improve the patency of a femorocrural PTFE bypass with a distal vein cuff despite the fact that the flow values increased both in the intraoperative measurements and during the immediate postoperative surveillance. The adjuvant av-fistula increased graft flow significantly also in a poor outflow venous bypass, but regardless of this the outcome was no improved. The adjuvant av-fistula rarely caused adverse effects. In a group of diabetic patients, the flow in a vascular bypass graft was augmented by an internal av-fistula within a radial forearm flap and similarly in a patient with a previous free flap transfer, a high intraoperative graft flow was achieved due to the free flap shunt effect.

Myoblast transplantation and adenoviral VEGF-C transfer in porcine model of coronary artery disease

Heart failure is a common and highly challenging medical disorder. The progressive increase of elderly population is expected to further reflect in heart failure incidence. Recent progress in cell transplantation therapy has provided a conceptual alternative for treatment of heart failure. Despite improved medical treatment and operative possibilities, end-stage coronary artery disease present a great medical challenge. It has been estimated that therapeutic angiogenesis would be the next major advance in the treatment of ischaemic heart disease. Gene transfer to augment neovascularization could be beneficial for such patients. We employed a porcine model to evaluate the angiogenic effect of vascular endothelial growth factor (VEGF)-C gene transfer. Ameroid-generated myocardial ischemia was produced and adenovirus encoding (ad)VEGF-C or β-galactosidase (LacZ) gene therapy was given intramyocardially during progressive coronary stenosis. Angiography, positron emission tomography (PET), single photon emission computed tomography (SPECT) and histology evidenced beneficial affects of the adVEGF-C gene transfer compared to adLacZ. The myocardial deterioration during progressive coronary stenosis seen in the control group was restrained in the treatment group. We observed an uneven occlusion rate of the coronary vessels with Ameroid constrictor. We developed a simple methodological improvement of Ameroid model by ligating of the Ameroid–stenosed coronary vessel. Improvement of the model was seen by a more reliable occlusion rate of the vessel concerned and a formation of a rather constant myocardial infarction. We assessed the spontaneous healing of the left ventricle (LV) in this new model by SPECT, PET, MRI, and angiography. Significant spontaneous improvement of myocardial perfusion and function was seen as well as diminishment of scar volume. Histologically more microvessels were seen in the border area of the lesion. Double staining of the myocytes in mitosis indicated more cardiomyocyte regeneration at the remote area of the lesion. The potential of autologous myoblast transplantation after ischaemia and infarction of porcine heart was evaluated. After ligation of stenosed coronary artery, autologous myoblast transplantation or control medium was directly injected into the myocardium at the lesion area. Assessed by MRI, improvement of diastolic function was seen in the myoblast-transplanted animals, but not in the control animals. Systolic function remained unchanged in both groups.

Molecular mechanisms of hypertension-induced heart failure : Experimental studies with special emphasis on local renin-angiotensin system, cardiac metabolism and levosimendan

Hypertension is a major risk factor for stroke, ischaemic heart disease, and the development of heart failure. Hypertension-induced heart failure is usually preceded by the development of left ventricular hypertrophy (LVH), which represents an adaptive and compensatory response to the increased cardiac workload. Biomechanical stress and neurohumoral activation are the most important triggers of pathologic hypertrophy and the transition of cardiac hypertrophy to heart failure. Non-clinical and clinical studies have also revealed derangements of energy metabolism in hypertensive heart failure. The goal of this study was to investigate in experimental models the molecular mechanisms and signalling pathways involved in hypertension-induced heart failure with special emphasis on local renin-angiotensin-aldosterone system (RAAS), cardiac metabolism, and calcium sensitizers, a novel class of inotropic agents used currently in the treatment of acute decompensated heart failure. Two different animal models of hypertensive heart failure were used in the present study, i.e. hypertensive and salt-sensitive Dahl/Rapp rats on a high salt diet (a salt-sensitive model of hypertensive heart failure) and double transgenic rats (dTGR) harboring human renin and human angiotensinogen genes (a transgenic model of hypertensive heart failure with increased local RAAS activity). The influence of angiotensin II (Ang II) on cardiac substrate utilization and cardiac metabolomic profile was investigated by using gas chromatography coupled to time-of-flight mass spectrometry to detect 247 intermediary metabolites. It was found that Ang II could alter cardiac metabolomics both in normotensive and hypertensive rats in an Ang II receptor type 1 (AT1)-dependent manner. A distinct substrate use from fatty acid oxidation towards glycolysis was found in dTGR. Altered cardiac substrate utilization in dTGR was associated with mitochondrial dysfunction. Cardiac expression of the redox-sensitive metabolic sensor sirtuin1 (SIRT1) was increased in dTGR. Resveratrol supplementation prevented cardiovascular mortality and ameliorated Ang II-induced cardiac remodeling in dTGR via blood pressure-dependent pathways and mechanisms linked to increased mitochondrial biogenesis. Resveratrol dose-dependently increased SIRT1 activity in vitro. Oral levosimendan treatment was also found to improve survival and systolic function in dTGR via blood pressure-independent mechanisms, and ameliorate Ang II-induced coronary and cardiomyocyte damage. Finally, using Dahl/Rapp rats it was demonstrated that oral levosimendan as well as the AT1 receptor antagonist valsartan improved survival and prevented cardiac remodeling. The beneficial effects of levosimendan were associated with improved diastolic function without significantly improved systolic changes. These positive effects were potentiated when the drug combination was administered. In conclusion, the present study points to an important role for local RAAS in the pathophysiology of hypertension-induced heart failure as well as its involvement as a regulator of cardiac substrate utilization and mitochondrial function. Our findings suggest a therapeutic role for natural polyphenol resveratrol and calcium sensitizer, levosimendan, and the novel drug combination of valsartan and levosimendan, in prevention of hypertension-induced heart failure. The present study also provides a better understanding of the pathophysiology of hypertension-induced heart failure, and may help identify potential targets for novel therapeutic interventions.

Critical leg ischaemia with tissue loss : a challenge for the vascular surgeon

There is a widespread reporting habit of combining the outcomes for patients with rest pain (Fontaine III) and tissue loss (Fontaine IV) under the single category of critical leg ischaemia (CLI). This study focused on patients with ischaemic tissue loss treated with infrainguinal bypass surgery (IBS). All patients included in the study were treated at Helsinki University Central Hospital in 2000-2007. First, ulcer healing time after IBS and factors influencing healing time were prospectively assessed in 2 studies including 148 and 110 patients, respectively. Second,the results of redo IBS were retrospectively evaluated in 593 patients undergoing primary IBS for CLI with tissue loss . Third,long-term outcome were retrospectively analysed in 636 patients who underwent IBS for CLI with tissue loss . Fourth, the outcome of IBS was retrospectively compared with endovascular treatment (PTA) of the infrapopliteal arteries in 1023 CLI patients. Fifth, the influence multidrug resistant Pseudomans aeruginosa (MDR Pa) bacteria contamination in CLI patients treated with IBS was retropectively assessed. Sixty-four patients with positive MDR Pa -culture were matched with 64 MDR Pa - negative controls. Complete ulcer healing rate, including the ischemic ulcers and incisional wounds, was 40% at 6 months after IBS and 75% at one year. Diabetes was a risk factor for prolonged complete ulcer healing time. Ischaemic tissue lesions located in mid-and hindfoot healed poorly. At one year after IBS 50% of the patients were alive with salvaged leg and completely healed ulcers. The absence of gap between tertiary graft patency and leg salvage rates indicates the importance of a patent infrainguinal graft to save a leg with ischaemic tissue loss. Long-term survival for patients with ischaemic tissue loss was poor, 38% at 5 years. Only 30% of the patients were alive without amputation at 5 years. Several of the patient comorbidities increased independently the mortality risk; coronary artery disease, renal insufficiency, chronic obstructive lung disease and high age. When both PTA and bypass is feasible, infrapopliteal PTA as a first-line strategy is expected to achieve similar long-term results to bypass surgery in CLI when redo surgery is actively utilized. MDR Pa in a patient with CLI should be considered as a serious event with increased risk of early major amputation or death. Conclusion: Despite a successful infrainguinal bypass healing of the ischaemic ulcers and incisional wounds ulcer healing is a slow process especially in diabetics. Bypass surgery and PTA improve the outcome of the ischaemic leg but the mortality rate of the patients is high due to their severe comorbidities.

High-risk patients and high-risk grafts in infrainguinal bypass for critical limb ischaemia

The main purpose of revascularization procedures for critical limb ischaemia (CLI) is to preserve the leg and sustain the patient s ambulatory status. Other goals are ischaemic pain relief and healing of ischaemic ulcers. Patients with CLI are usually old and have several comorbidities affecting the outcome. Revascularization for CLI is meaningless unless both life and limb are preserved. Therefore, the knowledge of both patient- and bypass-related risk factors is of paramount importance in clinical decision-making, patient selection and resource allocation. The aim of this study was to identify patient- and graft-related predictors of impaired outcome after infrainguinal bypass for CLI. The purpose was to assess the outcome of high-risk patients undergoing infrainguinal bypass and to evaluate the usefulness of specific risk scoring methods. The results of bypasses in the absence of optimal vein graft material were also evaluated, and the feasibility of the new method of scaffolding suboptimal vein grafts was assessed. The results of this study showed that renal insufficiency - not only renal failure but also moderate impairment in renal function - seems to be a significant risk factor for both limb loss and death after infrainguinal bypass in patients with CLI. Low estimated GFR (PIENEMPI KUIN 30 ml/min/1.73 m2) is a strong independent marker of poor prognosis. Furthermore, estimated GFR is a more accurate predictor of survival and leg salvage after infrainguinal bypass in CLI patients than serum creatinine level alone. We also found out that the life expectancy of octogenarians with CLI is short. In this patient group endovascular revascularization is associated with a better outcome than bypass in terms of survival, leg salvage and amputation-free survival especially in presence of coronary artery disease. This study was the first one to demonstrate that Finnvasc and modified Prevent III risk scoring methods both predict the long-term outcome of patients undergoing both surgical and endovascular infrainguinal revascularization for CLI. Both risk scoring methods are easy to use and might be helpful in clinical practice as an aid in preoperative patient selection and decision-making. Similarly than in previous studies, we found out that a single-segment great saphenous vein graft is superior to any other autologous vein graft in terms of mid-term patency and leg salvage. However, if optimal vein graft is lacking, arm vein conduits are superior to prosthetic grafts especially in infrapopliteal bypasses for CLI. We studied also the new method of scaffolding suboptimal quality vein grafts and found out that this method may enable the use of vein grafts of compromised quality otherwise unsuitable for bypass grafting. The remarkable finding was that patients with the combination of high operative risk due to severe comorbidities and risk graft have extremely poor survival, suggesting that only relatively fit patients should undergo complex bypasses with risk grafts. The results of this study can be used in clinical practice as an aid in preoperative patient selection and decision-making. In the future, the need of vascular surgery will increase significantly as the elderly and diabetic population increases, which emphasises the importance of focusing on those patients that will gain benefit from infrainguinal bypass. Therefore, the individual risk of the patient, ambulatory status, outcome expectations, the risk of bypass procedure as well as technical factors such as the suitability of outflow anatomy and the available vein material should all be assessed and taken into consideration when deciding on the best revascularization strategy.