The United States Registry for Fibromuscular Dysplasia

Peripheral artery disease of the lower extremities is a common disease and present in 15% to 20% of persons older than 65 years. Endovascular or surgical therapy fails or is not applicable in approximately one fourth of patients who would need revascularization therapies, which makes alternative approaches such as arteriogenesis (the positive remodeling of preformed collateral arterioles) necessary. Despite the fact that numerous studies have pursued the important therapeutic strategy of improving collateral function, there is no method available to quantify collateral arterial function of the lower limb and thus to determine therapeutic effects. The present study demonstrates for the first time a quantitatively assessed functional and clinically relevant collateral circulation in the lower limb. Using direct invasive pressure measurements in humans, we show that collateral flow index of the superficial femoral artery in the absence of any significant stenosis amounts to more than half the normal antegrade flow at rest (4517% after 1 minute, 5517% after 3 minutes). The amount of collateral flow observed in the present study is remarkably high, especially compared with what has been described previously for normal (188%) and stenotic (2215%) coronary arteries. Importantly, this preexistent collateral blood supply in the absence of significant stenoses is sufficient to completely prevent symptoms during 5 minutes of acute ischemia at rest. Because only indirect and weak end points have been used in past studies to evaluate collateral growth, we propose that the method described in the present study may possibly be used as a gold standard in future clinical studies.

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Fibromuscular dysplasia (FMD) is nonatherosclerotic, noninflammatory vascular disease that may result in arterial stenosis, occlusion, aneurysm, or dissection.1–3 The cause of FMD and its prevalence in the general population are not known.4 FMD has been reported in virtually every arterial bed but most commonly affects the renal and extracranial carotid and vertebral arteries (in ≈65% of cases).5 The clinical manifestations of FMD are determined primarily by the vessels that are involved. When the renal artery is involved, the most frequent finding is hypertension, whereas carotid or vertebral artery FMD may lead to dizziness, pulsatile tinnitus, transient ischemic attack (TIA), or stroke. There is an average delay from the time of the first symptom or sign to diagnosis of FMD of 4 to 9 years.5,6 This is likely because of a multitude of factors: the perception that this is a rare disease and thus FMD is not considered in the differential diagnosis, the reality that FMD is poorly understood by many healthcare providers, and the fact that many of the signs and symptoms of FMD are nonspecific, thus leading the clinician down the wrong diagnostic pathway. A delay in diagnosis can lead to impaired quality of life and poor outcomes such as poorly controlled hypertension and its sequelae, TIA, stroke, dissection, or aneurysm rupture. It should also be noted that FMD may be discovered incidentally while imaging is performed for other reasons or when a bruit is heard in the neck or abdomen in an asymptomatic patient without the classic risk factors for atherosclerosis. The first description of FMD is attributed to Leadbetter and Burkland7 in a 5½-year-old boy with severe hypertension and a renal artery partially occluded by an intra-arterial mass of smooth muscle. He underwent a unilateral nephrectomy of an …

58 - Fibromuscular Dysplasia

Fibromuscular dysplasia (FMD) is a nonatherosclerotic vascular disease that most commonly affects the renal, carotid, and vertebral arteries.1 Renal FMD is associated with renovascular hypertension, and patients may be referred for revascularization, generally with balloon angioplasty. We report a series of 2 patients with renal artery FMD who developed stent fracture. A 16-year-old girl was seen for a second opinion on renal FMD. Hypertension was diagnosed at the age of 13 years and initially treated medically; however, bilateral renal artery angioplasty was subsequently performed for poorly controlled blood pressure. She subsequently underwent placement of a drug eluting stent in the right renal artery for restenosis. Although she initially improved, there was gradual worsening of her blood pressure control. Noninvasive testing was consistent with severe restenosis of the right renal artery stent. Renal arteriography revealed a severe stenosis estimated at 80% in the right renal artery (Figure 1). There was severe narrowing noted at the ostium, resulting in a 70 mm Hg gradient across the lesion. …

Objective: To assess the frequency of cervical and intracranial arteries involvement and associated clinical symptoms in consecutive patients with renal fibromuscular dysplasia (FMD) enrolled into ARCADIA-POL study. Design and method: From 183 patients with FMD enrolled into ARCADIA-POL study since 2015 (Polish-French collaboration) all consecutive 157 patients (132F, 25 M, mean age:45.1 ± 15.1 years) with renal FMD were analyzed. All patients underwent clinical evaluation: ABPM, biochemical evaluation, biobanking, duplex Doppler of cervical and abdominal arteries and whole body angio-CT including cervical and intracranial arteries. Results: Among 157 patients with renal FMD, 38 (24.2%) had coexisting FMD lesions in cervical and/or intracranial arteries and/or intracranial aneurysms: 17 (10.8%) patients in carotid, 7 (4.5%) patients in vertebral and 24 (15.3%) patients had lesions in intracranial arteries. Dissections of carotid arteries were present in 3 (1.9%) patients and vertebral artery dissections in 3 (1.9%) patients. In 10 (6.4%) pts internal carotid artery aneurysm and in 2 (1.3%) patients vertebral artery aneurysm were found. 18 (11.5%) patients had intracranial aneurysms: 15 (9.6%) patients had one aneurysm, 2 (1.3%) pts 2 aneurysms and 1 (0.6%) patient had 3 aneurysms. Patients with and without cervical and/or intracranial FMD lesions didn’t differ in terms of age, gender, clinical and ambulatory blood pressure levels, hypertension prevalence and number of antihypertensive medications. There were no significant differences in the prevalence of symptoms such as headaches, tinnitus, dizziness and cervical bruits between the patients with and without cervical and/or intracranial FMD. There was only a significant difference in the presence of Horner's syndrome between patients with and without cervical and/or intracranial FMD (16.7% vs.1.9%; p = 0.001, respectively). There was no difference in the prevalence of stroke, transient ischemic attack or intracranial bleeding between the groups. Conclusions: There were no specific clinical features suggesting the presence of FMD lesions and vascular complications in cervical and/or intracranial arteries in patients with confirmed renal FMD included into ARCADIA-POL STUDY. Our study showed that systematic evaluation of cervical and intracranial arteries in patients with renal FMD results in revealing relatively high prevalence of FMD lesions and vascular complications in cervical and/or intracranial arteries.

8:48 AM Abstract No. 18 - ■ FEATURED ABSTRACT Is fibromuscular dysplasia (FMD) underdiagnosed? A comparison of the prevalence of fmd seen in patients enrolled into the CORAL trial versus a single institution population of renal donor candidates

Fibromuscular dysplasia (FMD) is a nonatherosclerotic arterial disease that predominately affects women and is most commonly diagnosed in middle age. The natural history of FMD among patients diagnosed at an older age is not well understood. To examine the differences in clinical presentation, arterial bed involvement, vascular events, and need for vascular procedures between younger and older patients with FMD. Analysis of baseline data for patients enrolled in the US Registry for FMD as of December 15, 2016, at referral centers participating in the US Registry for FMD. Patients 18 years and older at the time of enrollment and those with only confirmed multifocal (string of beads type) FMD were included. Patients were categorized according to age at the time of diagnosis (≥65 years vs <65 years). Prevalence of specific symptoms, vascular events, and prior vascular procedures at the time of enrollment in the registry. A total of 1016 patients were included in the analysis, of whom, 170 (16.7%) were 65 years or older at the time of diagnosis. Older patients with FMD were more likely to be asymptomatic at the time of diagnosis (4.2% vs 1.4%; P = .02). Headache and pulsatile tinnitus, both common manifestations of FMD, were less common in older patients (40.5% vs 69.1%; P < .001 and 30% vs 44.6%; P < .001, respectively). Extracranial carotid arteries were more commonly involved in patients 65 years or older at time of diagnosis (87% vs 79.4%; P = .03). There was no difference in prevalence of renal artery involvement, number of arterial beds involved, or diagnosis of any aneurysm. Patients 65 years or older were less likely to have had a major vascular event (37.1% vs 46.1%; P = .03) and fewer had undergone a therapeutic vascular procedure (18.5% vs 33.1%; P < .001). In the US Registry for FMD, patients 65 years or older at the time of diagnosis of multifocal FMD were more likely to be asymptomatic, had lower prevalence of major vascular events, and had undergone fewer therapeutic vascular procedures than younger patients. Patients with multifocal FMD diagnosed at an older age may have a more benign phenotype and fewer symptoms.

Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e422 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e424 2. Recommendations for Duplex Ultrasonography to Evaluate Asymptomatic Patients With Known or Suspected Carotid Stenosis . . . . . . . . . . . . . . . . .e425 3. Recommendations for Diagnostic Testing in Patients With Symptoms or Signs of Extracranial Carotid Artery Disease . . . . . . . . . . . . .e426 4. Recommendations for the Treatment of Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e426 5. Recommendation for Cessation of Tobacco Smoking. . . . . . . . . . . . . . . . . . . . . . . . . . .e426 6. Recommendations for Control of Hyperlipidemia. . . . . . . . . . . . . . . . . . . . . . . . . . . . .e427 7. Recommendations for Management of Diabetes Mellitus in Patients With Atherosclerosis of the Extracranial Carotid or Vertebral Arteries. . . . . . . . . . . . …

Imaging description CT and MRI angiography provide a reliable and non-invasive method for diagnosis of renal fibromuscular dysplasia (FMD). The characteristic feature of renal FMD is a “string of beads” appearance of the mid- and distal renal artery due to the alternating stenosis and aneurysm formation (Figure 81.1). Axial imaging in combination with maximal intensity projection reconstructions are extremely helpful in making the diagnosis (Figure 81.2). Contrast-enhanced 3D MRA can also be used as an alternate to CTA (Figure 81.3). Care should be taken not to misinterpret the stepladder image reconstruction artifact, resulting from faulty data reconstruction that produces a gap or overlap between sections or from source images that are too thick, as FMD (Figure 81.4). Conventional angiography, although considered gold standard, is not frequently used due to its invasive nature and may be reserved for equivocal findings seen on CTA or MRA and for treatment. Importance Fibromuscular dysplasia is the second most common cause of renovascular hypertension, after atherosclerotic disease, affecting mostly young or middle-aged women. The disease is bilateral in two-thirds of the patients. It is classified according to the location of involvement within the vessel wall with medial fibroplasia accounting for 95% of cases. FMD is a non-inflammatory, non-atherosclerotic disease with presence of alternating areas of narrowing and small aneurysms causing the beaded appearance of the arteries. Vascular narrowing and dissections may occur. FMD may also involve other visceral arteries such as the hepatic artery as well as the carotid and vertebral arteries (Figure 81.5). Accurate diagnosis is important as the treatment of FMD is distinct from other causes of renal artery stensosis such as atherosclerotic disease or vasculitis and can be treated with percutaneous transluminal angioplasty with a very high success rate. Typical clinical scenario Renal FMD may be incidentally found on imaging in a young potential renal donor or in a young or middle-aged woman with hypertension refractory to medical therapy.

Objective: To assess the involvement of cervical and intracranial arteries and associated clinical symptoms in patients with renal fibromuscular dysplasia (FMD) enrolled into ARCADIA-POL study. Design and method: From 144 patients with confirmed FMD enrolled into ARCADIA-POL study in 2015, 127 patients (104F, 23 M, mean age:44.8 ± 15.9 years) were analyzed. All patients underwent clinical evaluation: ABPM, biochemical evaluation, biobanking, duplex Doppler of cervical and abdominal arteries and whole body angio-CT including cervical and intracranial arteries. Results: Among 127 patients with renal FMD, 31 (24.4%) had coexisting FMD lesions in cervical and/or intracranial arteries and/or intracranial aneurysms: 15 (11.8%) pts in carotid, 4 (3.1%) pts in vertebral and 19 (15.0%) pts in intracranial arteries. Dissections of carotid arteries were found in 4 (3.2%) pts and vertebral artery dissections in 3 (2.4%) pts. In 3 (2.4%) pts internal carotid artery aneurysm was found. 12 (9.5%) pts had intracranial aneurysms: 9 (7.1%) pts had one aneurysm, 2 (1.6%) pts 2 aneurysms, 1 (0.8%) pts 3 aneurysms and 1 (0.8%) pt 4 intracranial aneurysms. Patients with and without cervical and/or intracranial FMD lesions didn’t differ in terms of age, gender, clinical and ambulatory blood pressure levels, hypertension prevalence and number of antihypertensive medications. There was also no difference in the incidence of cervical and/or intracranial FMD lesions in patients with multifocal and unifocal lesions in renal arteries. There were no significant differences in the prevalence of symptoms such as headaches, tinnitus, dizziness and cervical bruits between the patients. There was only a significant difference in the presence of Horner's syndrome between patients with and without cervical and/or intracranial FMD (12.9% vs.2.4%; p = 0.017, respectively). There was no difference in the prevalence of stroke, transient ischemic attack or intracranial bleeding between the groups. Conclusions: There were no specific clinical features suggesting the presence of FMD lesions and vascular complications in cervical and/or intracranial arteries in patients with confirmed renal FMD included into ARCADIA-POL STUDY. Our study showed that systematic evaluation of cervical and intracranial arteries in patients with renal FMD resulted in revealing relatively high prevalence of FMD lesions and vascular complications in cervical and/or intracranial arteries.

A 38-year-old female presented to us with a history of fluctuating blood pressure. On physical examination, her blood pressure in the right arm was 180/110 mmHg. Physical examination revealed no other abnormalities. Her laboratory parameters were within normal limits. Renal artery duplex ultrasound was suggestive of significant stenosis in the left renal artery. Subsequent renal angiography demonstrated a classical string of beads appearance of both the renal arteries (saccular dilatations and constrictions) that spared the ostium; this was suggestive of fibromuscular dysplasia. The left renal artery also exhibited short-segment web-like stenosis (70% to 80%) in the mid-segment with a significant gradient across it (Fig. 1). Angioplasty of the stenotic segment was performed using an angioplasty balloon at a pressure of 10 atmospheres with good results (Fig. 2). After angioplasty, the patient's blood pressure normalized and she was discharged without any antihypertensive medications. At the 6-month follow-up, her blood pressure remained normal and she required no antihypertensive medications. Figure 1 (A) Renal angiography showing the classical string of beads appearance of the left renal artery with stenosis in the mid segment. (B) Renal angiography (higher resolution) showing the classical string of beads appearance of the left renal artery with ... Figure 2 (A) Digital subtraction angiography showing the classical string of beads appearance of the left renal artery with stenosis in the mid segment. (B) Digital subtraction angiography showing good dilatation of the stenosed segment-postangioplasty. Fibromuscular dysplasia is a noninflammatory, nonatherosclerotic vascular disease that commonly involves the renal and internal carotid arteries; however, it can involve any arterial bed. Renal fibromuscular dysplasia usually affects females from 15 to 50 years of age and accounts for around 10% of cases of renal artery stenosis. Renal fibromuscular dysplasia is classified based on the predominant arterial layer involved: intima, media, or adventitia. Involvement of the media is further subdivided into medial, perimedial, and hyperplastic medial fibromuscular dysplasia. The three most common and classically described subtypes include medial (70% of cases), perimedial (15% to 25%), and intimal fibrodysplasias (1% to 2%). The classical angiographic string of beads appearance is seen in medial and perimedial fibromuscular dysplasias. It is characterized by alternating stenoses and aneurysms and frequently involves the bilateral renal arteries. The most accurate method for diagnosis of fibromuscular dysplasia remains catheter-based angiography.

Fibromuscular dysplasia (FMD) is an idiopathic, segmental, non-atherosclerotic and non-inflammatory disease, which leads to stenosis of small- and medium-sized arteries. With cerebrovascular FMD, renal artery FMD is the most frequent presentation of the disease. The prevalence of renal FMD remains elusive but an estimate of 3–5% seems reasonable. Renal artery FMD is usually diagnosed incidentally, on the occasion of a work-up for hypertension, or seldom following renal artery dissection. The typical patient with renal artery FMD is a ~50-year-old woman with hypertension, but FMD can also be diagnosed in men and at all ages of life. In children and adolescents, it is often associated with severe hypertension and cardiovascular damage. In most cases, CT-/MR-angiography may be considered as the test of choice for both screening and diagnosis of renal FMD, in association with duplex ultrasound evaluation, which provides additional hemodynamic information. In view of the high (>50%) prevalence of multivessel FMD, once a lifetime exploration of all vascular beds from brain to pelvis is recommended. Detection of cerebrovascular FMD is of particular importance, due to its high prevalence and potential dramatic consequences of complications. Smoking cessation is strongly advised. Antiplatelet treatment deserves to be considered on a case-by-case basis. In patients with hypertension, strict blood pressure control is required. Revascularization—usually by percutaneous balloon angioplasty without stenting—is justified, especially in young patients, in patients with recent onset or severe hypertension, as well as in rare cases of deterioration of renal function, in the presence of arguments in favour of a hemodynamically significant renal artery stenosis. FMD may be familial in up to 10% of cases; therefore, screening for FMD should be considered in relatives with suggestive symptoms. Finally, as patients with FMD may progress or develop complications, a lifelong yearly follow-up, tailored for each patient, is justified. The development of the US and European/International FMD registries and associated studies will undoubtedly shed new light on FMD and allow substantial progress in the understanding and management of the disease in the next decade.

Objective: To present preliminary evaluation of vascular bed involvement and vascular complications in patients with fibromuscular dysplasia (FMD) enrolled to ARCADIA-POL registry. Design and method: The first 84 patients (59F[70.2%], 25M[29.8%], mean age: 42.5 ± 14.8 years, range:18–72) with confirmed FMD in any vascular bed were enrolled in 2015 in ARCADIA-POL registry (instituted on the basis of as Polish-French collaboration). A standardized FMD data form was used for data collection. All patients underwent detailed clinical evaluation including ambulatory blood pressure monitoring (ABPM), biochemical evaluation, biobanking, duplex Doppler of carotid and abdominal arteries and whole body angio-CT. Results: In the analyzed group FMD was identified in renal arteries in 74 (88.1%) patients, bilaterally in 29 (39.2%) patients as well as in carotid, intracranial and vertebral arteries in 14 (16.7%), 14 (16.7%) and 6 (7.1%) patients, respectively. FMD was also identified in celiac trunk and mesenteric, iliac and splenic arteries in 12(14.3 %), 7(8.3%), and 6(7.1%) patients, respectively. Evaluating degree of renal artery stenosis on duplex Doppler and angio-CT, significant stenosis was identified in 19 (25.7%) patients (in this group 8 patients had restenosis after previous intervention) whereas non-significant stenosis was found in 55 (74.3%) patients (in this group 9 patients had a history of intervention on renal artery). In 39 patients (46.4%) FMD was identified in two or more vascular bed. Two vascular beds were involved in 31% (26 pts), three in 11.9% (10 pts), four in 2.4 % (2 pts) and five in 1.2 % (1 pt). Arterial dissection(s) and aneurysms in various vascular beds were found in 14.3% and 26.2% of patients respectively. Severe FMD defined as first onset of FMD <30 years, affecting at least 3 vascular beds complicated with thrombosis or dissection requiring an endovascular or surgical repair, with no inflammatory background was identified in 2 patients (2.4%). Conclusions: Preliminary data of ARCADIA-POL registry showed that renal FMD was the most frequent, but also cerebrovascular FMD occurred in relatively large proportion of patients. Our data revealed high incidence of FMD lesions coexisting in different vascular beds as well as relatively frequent occurrence of vascular complications.

Fibromuscular dysplasia (FMD) is a rare idiopathic, segmental, noninflammatory and nonatherosclerotic arteriopathy of medium-sized arteries. It is classically considered to be a disease of young and middle adulthood, with females more commonly affected than males. FMD is a systemic disease. Although historically considered to be rare, cerebrovascular FMD (C-FMD) has now been recognized to be as common as the renovascular counterpart. Extracranial carotid and vertebral arteries are the most commonly involved vascular territories in C-FMD with the clinical presentation determined by vessels affected. Common symptoms include headaches and pulsatile tinnitus, with transient ischemic attacks, ischemic stroke and subarachnoid or intracerebral hemorrhage constituting the more severe clinical manifestations. Cervical artery dissection involving carotids more often than vertebral arteries and intracranial aneurysms account for the cerebrovascular pathologies detected in C-FMD. Our understanding regarding C-FMD has been augmented in the recent past on account of dedicated C-FMD data from North American, European and other international FMD cohorts. In this review article, we provide an updated and comprehensive overview on epidemiology, clinical presentation, etiology, diagnosis and management of C-FMD.