Objective: Endurance athletes such as cyclists may develop intermittent claudication owing to iliac artery endofibrosis after long-lasting extreme hemodynamic challenges. This study investigated short-term (<1.5 years) and long-term (>5 years) satisfaction and safety after a surgical endarterectomy and autologous patching. Methods: Data of endurance athletes who underwent an endarterectomy for flow limitation of the iliac artery owing to endofibrosis between 1997 and 2015 in one center were studied. Maximal cycling exercise tests, ankle-brachial index with flexed hips, echo-Doppler examination (peak systolic velocity), and contrast-enhanced magnetic resonance angiography were performed before and 6 to 18 months after surgery. Short-term and long-term satisfaction were evaluated using questionnaires. Potential patch dilatation was assessed using echo-Doppler. Results: Analysis of 68 patients (79 legs; 55.7% males, median age at the time of surgery, 34 years; interquartile range, 2641 years) demonstrated that cycling workload at symptom onset improved from 226 +/- 97 to 333 +/- 101 (P <.001) Watts. Peak workload increased from 326 +/- 111 to 352 +/- 93 Watts (P <.001). Ankle-brachial index with flexed hips increased from 0.34 (interquartile range [IQR], 0.00-0.47) to 0.59 (IQR, 0.51-0.69; P <.001). Peak systolic velocity with extended and flexed hip decreased from 2.04 m.sec(-1) (IQR, 1.52-2.56 m.3sec(-1)) to 1.25 m.sec(-1) (IQR, 0.92-1.62 m.sec(-1); P <.001) and 2.40 m.sec(-1) (IQR, 1.81-2.81 m.sec(-1)) to 1.15 m.sec(-1) (IQR, 0.97-1.60 m.sec(-1); P <.001), respectively. Thirty-day major complication rate was 5.1% (hematoma requiring evacuation n(Legs) = 2, septic bleeding from deep infection n(Legs) = 1, and iliac occlusion requiring thrombectomy n(Legs) = 1). In the short term, 91.2% of patients reported symptom reduction with a 93.7% overall satisfaction rate. After a median of 11.1 years (IQR, 7.8-17.6 years), the overall satisfaction was 91.7%; 94.5% of patients reported persistent symptomreduction. Patch dilatation of >20 mm was observed in two patients. Linear mixed model analysis revealed no alarming patch dilatation in the long term. Conclusions: Endarterectomy with an autologous patch for intermittent claudication owing to iliac artery endofibrosis in endurance athletes shows high rates of patient satisfaction and symptomreduction in both the short and long term. The risk of surgical complications or patch dilatation is mild. A surgical intervention for flow limitation of the iliac artery owing to endofibrosis is safe and successful.

Objective: Endurance athletes are prone to develop flow limitations in iliac arteries (FLIA). Especially in cyclists and ice speed skaters, excessive hemodynamic loading coupled with hip hyperflexion may cause kinking in lengthened iliac arteries necessitating surgical correction. This study investigated the short-term (<= 1.5 years) and long-term (>= 5 years) satisfaction of operative shortening of the iliac artery in endurance athletes. Methods: All patients who were diagnosed and operated for FLIA owing to lengthened and kinked iliac arteries between 1997 and 2015 in one center were analyzed. Short-term follow-up consisted of an incremental maximal cycling test, ankle-brachial index with flexed hips, echo-Doppler examination with peak systolic velocity measurements and contrast-enhanced magnetic resonance angiography before and 6 to 18 months after surgery. Both short-and long-term satis-faction were assessed using questionnaires. Results: A total of 83 patients (90 operated legs; 96.7% males; median age of 34 years at the time of surgery; interquartile range [IQR], 29-47) were analyzed. In the short-term, 87.5% reported symptom reduction with an 86.4% overall satis-faction rate. Symptom-free cycling improved from 272 +/- 84 W to 384 +/- 101 W (P < .001), whereas the maximal workload increased from 419 +/- 72 W to 428 +/- 67 W (P = .01). The ankle-brachial index with flexed hips increased from 0.55 (IQR, 0.45-0.65) to 0.62 (IQR, 0.52-0.74; P = .008), and the peak systolic velocity measured with hips flexed decreased from 2.50 m/s (IQR, 1.77-3.13 m/s) to 1.57 m/s (IQR, 1.20-2.04 m/s; P < .001). After a median of 12 years (IQR, 9.0-15.4 years), symptoms were still decreased in 84.1% of patients with an 81.2% overall satisfaction rate (79.5% response rate). Three patients needed a reintervention (recurrent FLIA, n = 2; failure, n = 1). Conclusions: Operative shortening of a lengthened and kinked iliac artery causing FLIA is successful both in the short-and long-term.

Objective: Endurance athletes can develop intermittent claudication due to sports-related flow limitations of the iliac artery (FLIA) caused by arterial kinking. In the present study, we investigated the short- and long-term efficacy of an operative release for iliac artery kinking. Methods: Between 1996 and 2015, all patients with a diagnosis of FLIA due to iliac artery kinking without substantial arterial stenosis (<15%) or an excessive arterial length (vessel length to straight ratio, <1.25) who had undergone surgery were included. The short-term follow-up protocol consisted of cycling tests, the ankle brachial index with a flexed hip, and Doppler echography examinations to determine the peak systolic velocity before and 6 to 18 months after surgery. Additionally, the short- and long-term efficacy were evaluated using questionnaires. Results: A total of 142 endurance athletes (155 legs; 88.4% male; median age, 26 years; interquartile range [IQR], 22-31 years) were available for analysis. In the short term, the symptoms had decreased in 83.9% of the patients, with an overall 80.3% satisfaction rate. Power during a maximal cycling test had improved from 420 W (IQR, 378-465 W) to 437 W (IQR, 392-485 W; P<.001). The symptom-free workload had increased from 300 W (IQR, 240-340 W) to 400 W (IQR, 330-448 W; P<.001). The postexercise ankle brachial index with a flexed hip had increased from 0.53 (IQR, 0.40-0.61) to 0.57 (IQR, 0.47-0.64; P=.002), and the peak systolic velocity with a flexed hip had decreased from 1.88 m/s (IQR, 1.45-2.50 m/s) to 1.52 m/s (IQR, 1.19-2.07 m/s; P<.001). Postoperative imaging studies revealed some degree kinking in 33.9%, mostly asymptomatic. The long-term results were evaluated after a median of 15.2 years (IQR, 10.9-19.5 years). The athletes had cycled an additional 125.500 km (IQR, 72.00-227.500 km), which was approximately equal to the 131.000 km (IQR, 98.250-220.000 km) cycled before the diagnosis of FLIA. On the long term, 63.9% of the athletes reported persistent reduction of complaints, with an overall 59.1% satisfaction rate. Eight patients had required reintervention, six because of treatment failure and two because of newly developed FLIA. Conclusions: Operative iliac artery release for sports-related functional kinking in the absence of stenosis or an excessive vessel length was effective for most athletes in the short and long term.

OBJECTIVES:Approximately one in five professional cycling athletes will eventually develop a sport-related vascular problem. However, detecting such flow limitation is a diagnostic challenge as the sensitivity of the currently available standard diagnostic tools is limited.METHODS:Here we present an athlete with exercise-induced pain and weakness of the left leg. During the physical examination, pulsations of the femoral artery were palpable but less prominent. He was analyzed in an ongoing research project aimed at improving methods detecting sport-related leg flow limitations.RESULTS:During functional testing, the ankle-brachial index of the left leg was moderately lowered. However, results of near-infrared spectroscopy and pedal power measurements were largely abnormal suggesting a severe flow limitation.CONCLUSION:Combining post-exercise ankle-brachial index, near-infrared spectroscopy, and pedal power measurements as routine diagnostic functional testing suggested a severe arterial flow inflow limitation. Conventional diagnostics encompassing duplex-Doppler echography and magnetic resonance angiography confirmed a femoral artery occlusion.CLINICAL TRIAL REGISTRATION:https://www.trialregister.nl/ identifier is Trial NL8557.Abbreviations: NIRS: Near-Infrared Spectroscopy; PPM: Pedal Power Measurements; ABI: Ankle Brachial Index; PSV: Peak Systolic Velocity.

OBJECTIVE:High-performance athletes can develop symptomatic arterial flow restriction during exercise caused by endofibrosis. The pathogenesis is poorly understood; however, coagulation enzymes, such as tissue factor (TF) and coagulation factor Xa, might contribute to the fibrotic process, which is mainly regulated through activation of protease-activated receptors (PARs). Therefore, the aim of this explorative study was to evaluate the presence of coagulation factors and PARs in endofibrotic tissue, which might be indicative of their potential role in the natural development of endofibrosis. METHODS:External iliac arterial specimens with endofibrosis (n = 19) were collected during surgical interventions. As control, arterial segments of the external iliac artery (n = 20) were collected post mortem from individuals with no medical history of cardiovascular disease who donated their body to medical science. Arteries were paraffinized and cut in tissue sections for immunohistochemical analysis. Positive staining within lesions was determined with ImageJ software (National Institutes of Health, Bethesda, Md). RESULTS:Endofibrotic segments contained a neointima, causing intraluminal stenosis, which was highly positive for collagen (+150%; P < .01) and elastin (+148%; P < .01) in comparison with controls. Intriguingly, endofibrosis was not limited to the intima because collagen (+213%) and elastin (+215%) were also significantly elevated in the media layer of endofibrotic segments. These findings were accompanied by significantly increased α-smooth muscle actin-positive cells, morphologically compatible with the presence of myofibroblasts. In addition, PAR1 and PAR4 and the membrane receptor TF were increased as well as coagulation factor X. CONCLUSIONS:We showed that myofibroblasts and the accompanying collagen and elastin synthesis might be key factors in the development of endofibrosis. The special association with increased presence of PARs, factor X, and TF suggests that protease-mediated cell signaling could be a contributing component in the mechanisms leading to endofibrosis.

Endurance cyclists have a substantial risk to develop flow limitations in the iliac arteries during their career. These flow limitations are due to extreme hemodynamic stress which may result in functional arterial kinking and/or intravascular lesions. Early diagnosis may improve outcome and could prevent the necessity for surgical vascular repair. However, current diagnostic techniques have unsatisfactory sensitivity and cannot be applied during exercise. Near-infrared spectroscopy (NIRS) has shown great diagnostic potential in peripheral vascular disease and might bring a solution since it measures tissue oxygenation in real time during and after exercise. This report describes the first experiences of the application of NIRS in the vastus lateralis muscle during and after maximal graded cycling exercise in ten healthy participants and in three patients with flow limitations due to (1) subtle functional kinking, (2) an intravascular lesion, and (3) severe functional kinking. The results are put into perspective based on an empirically fitted model. Delayed recovery, showing clearly different types of patterns of tissue reoxygenation after exercise, was found in the affected athletes compared with the healthy participants. In the patients that had kinking of the arteries, tissue reoxygenation was clearly more delayed if NIRS was measured in provocative position with flexed hip. In this pilot experiment, clearly distinctive reoxygenation patterns are observed during recovery consistent with severity of flow limitation, indicating that NIRS is a promising diagnostic tool to detect and grade arterial flow limitations in athletes. Our findings may guide research and optimization of NIRS for future clinical application.

Background: High performance athletes can develop symptomatic arterial flow restriction during exercise, caused by endofibrosis. The disease is an poorly understood condition, characterized by fibrosis of the external iliac artery. Pathophysiological processes involved in the development of endofibrosis are unknown. However, evidence shows that coagulation enzymes such as thrombin and factor Xa (FXa) can influence pro-fibrotic processes, mainly mediated through activation of protease activated receptors (PAR). Aim: We investigated the immunohistochemical characteristics of endofibrotic lesions to determine the potential role of coagulation proteases and their receptors in development of endofibrosis. Methods: 19 arterial endofibrotic specimens were collected during endarterectomy. As controls 20 arterial segments of the external iliac artery were collected post mortem from individuals who donated their body to medical science, with no medical history of cardiovascular disease. Acquired arteries were paraffinized and cut in tissue sections for immunohistochemical staining. Data were analyzed using a Mann-Whitney U test. A 2-tailed p<0.05 was considered as statistically significant. Results: Endofibrotic segments contained a neo-intima, resulting in an intraluminal stenosis (42±14%). Compared to the intima of controls, endofibrotic lesions were highly positive for collagen (47±16% vs 15±5%, p=0.0001) and elastin (38±9% vs 16±4%, p=0.0003). These findings were accompanied by significantly increased alpha smooth muscle actin expression (51±10% vs 36±11%, p=0.01), which morphologically appeared to be myofibroblasts in endofibrotic lesions; which were hardly present in controls. In addition, PAR1 (49±17% vs 22±10%, p=0.0003) and PAR4 (39±8% vs 10±4%, p<0.0001) were upregulated and proenzymes of their activators, prothrombin and factor X were abundantly present in endofibrosis. Conclusion: This is the first study to show that myofibroblasts, and the subsequent collagen and elastin production, might be key factors in the development of endofibrosis. The special association suggests that these processes may be regulated through activation of PARs by coagulation proteases, which needs to be established in further studies.

Non-atherosclerotic arterial disease of the lower limbs is rare. Healthcare professionals are more familiar with atherosclerotic disease of the lower limbs and, therefore, patients who have non-atherosclerotic disease frequently present late, after they have been investigated for a wide range of other conditions. There is a wide spectrum of pathologies from congenital to acquired conditions. Some of the diseases, such as fibromuscular dysplasia, may have other arterial involvement, whilst others are confined to specific arteries of the lower limb. Although some of the conditions have a benign course, most are associated with significant reduction in quality of life in a relatively young, otherwise fit population. Vascular surgeons should therefore be aware of the most notable of these rare conditions. Specifically, they should be able to identify them in everyday clinical practice, understand their natural history and the indications for and outcomes of surgical intervention.

Introduction: High performance athletes, predominantly professional cyclists, can develop symptomatic arterial flow restriction in one or both legs during exercise. The ischemic symptoms are caused by endofibrosis and/or kinking of the external iliac artery. Because these athletes are young and have no classic risk factors for atherosclerosis, endofibrosis and atherosclerosis are considered different disease entities. We compared histology of endofibrotic lesions from young sportsmen with atherosclerotic lesions of the external iliac artery in elderly individuals.Methods and Results: Nineteen external iliac endarterectomy specimens from 18 cyclists (age 29 +/- 8 years) were compared with 42 external iliac segments from 22 elderly individuals (82 +/- 10 years). Ten arteries from elderly individuals revealed an intimal area that was >= 25% of the area encompassed by the internal elastic lamina and were considered atherosclerotic lesions. Stenosis was higher in patients (65% [interquartile range 50-75]) than in controls (11% [7-24]) (P < .0001). The endofibrotic lesions revealed loose connective tissue with moderate to high cellularity. Both in endofibrosis and atherosclerosis, most cells in the lesion were smooth muscle actin positive. In the endofibrosis specimens, loose fibers of collagen were observed, whereas in the atherosclerotic lesions collagen was mostly densely packed. Calcification of the lesion was not observed in endofibrotic lesions, whereas calcium deposition was observed in 80% of atherosclerotic lesions. Lymphocytes were present in 21% of endofibrotic lesions and in 80% of atherosclerotic cases. Macrophages were observed in 16% of endofibrotic lesions and in all atherosclerotic plaques. Luminal thrombosis was observed in one case of endofibrosis.Conclusion: In the external iliac artery, atherosclerotic lesions and endofibrotic lesions of high performance cyclists have distinct morphologic characteristics. Endofibrosis in the external iliac artery may serve as soil for luminal thrombosis. (J Vasc Surg 2008;48:1458-63.)

Approximately one in five top-level cyclists will develop sports-related flow limitations in the iliac arteries. These flow limitations may be caused by a vascular lumen narrowing due to endofibrotic thickening of the intima and/or by kinking of the vessels. In some athletes, extreme vessel length contributes to this kinking. Endofibrotic thickening is a result of a repetitive vessel damage due to haemodynamic and mechanical stress. Atherosclerotic intimal thickening is seldom encountered in these young athletes. This type of sports-related flow limitation shows no relationship with the classical risk factors for atherosclerosis like smoking, hypercholesterolaemia or family predisposition for arterial diseases.The patient's history is paramount for diagnosis. If an athlete reports typical claudication-like complaints in a leg at maximal effort, which disappear quickly at rest, approximately two out of three will have a flow limitation in the iliac artery. In current (sports) medical practice, this diagnosis is often missed, since a vascular cause is not expected in this healthy athletic population. Even if suspected, the routinely available diagnostic tests often appear insufficient. Definite diagnosis can be made by a combination of the patient's history and special designed tests consisting of a maximal cycle ergometer test with ankle blood pressure measurements and/or an echo-Doppler examination with provocative manoeuvres like hip flexion and exercise.Conservative treatment consists of diminishing or even completely stopping the provocative sports activity. If conservative treatment is insufficient or deemed unacceptable, surgical treatment might be considered. As surgery needs to be tailored to the underlying lesions, a detailed analysis before surgery is necessary. Standard clinical tests, used for visualising atherosclerotic diseases, are inadequate to identify and quantify the causes of flow limitations. Echo-Doppler examination and magnetic resonance angiography with both flexed and extended hips have been proven to be adequate tools. In particular, overprojection and eccentric location of the lesions seriously limit the usefulness of a two-dimensional technique like digital subtraction angiography.In the early stages, when kinking has not yet led to intimal thickening or excessive lengthening, simple surgical release of the iliac artery is effective. However, for patients with excessive vessel lengths or extensive endofibrotic thickening, a vascular reconstruction may be necessary. A major drawback of these interventions is that long-term effects and complications are unknown.As both the diagnostic methods and the treatments for this type of flow limitation differ substantially from routine vascular procedures, these patients should be examined in specialised research centres with appropriate diagnostic tools and medical experience.