Multifocal Fibromuscular Dysplasia Research Articles

Successful emergency renal auto-transplantation in a child with renovascular disease.

Renal artery occlusion is a rare but potentially catastrophic complication of paediatric endovascular renal artery intervention. Emergency auto-transplantation may be required to salvage the kidney; to date this has only been described in adults. We report our experience of performing emergency kidney auto-transplantation following acute renal artery thrombosis in a child undergoing redo renal artery angioplasty A 20-month-old boy presented with refractory hypertension and hypertensive cardiomyopathy secondary to multifocal fibromuscular dysplasia (FMD) with a single functioning kidney. Acute thrombosis of the renal artery during redo-endovascular balloon angioplasty necessitated emergency renal auto-transplantation. Subsequent acute kidney injury was reversible with benefit to renal function in the medium-term despite prolonged warm ischaemic time of two hours. We recommend that high-risk patients undergoing renal artery intervention do so at centres with on-site renal and vascular surgical backup.

From Fibromuscular Dysplasia to Arterial Dissection and Back.

Fibromuscular dysplasia (FMD) is an idiopathic and systemic non-inflammatory and non-atherosclerotic arterial disease. Fifteen to 25% of patients with FMD present with arterial dissection in at least one arterial bed. Conversely, a substantial number of patients with renal, carotid, and visceral dissection have underlying FMD. Also, while few patients with FMD develop coronary artery dissection, lesions suggestive of multifocal FMD have been reported in 30-80% of patients with spontaneous coronary artery dissection (SCAD), and the relation between these two entities remains controversial. The frequent association of FMD with arterial dissection, both in coronary and extra-coronary arteries raises a number of practical and theoretical questions: (i) Are FMD and arterial dissections two different facets of the same disease or distinct though related entities? (ii) Is SCAD just a manifestation of coronary FMD or a different disease? (iii) What is the risk and which are predictive factors of developing arterial dissection in a patient with FMD? (iv) What proportion of patients who experienced an arterial dissection have underlying FMD, and does this finding influence the risk of subsequent arterial complications? In this review we will address these different questions using fragmentary, mostly cross-sectional evidence derived from large registries and studies from Europe and the United States, as well as arguments derived from demographics, clinical presentation, imaging, and when available histology and genetics. From there we will derive practical consequences for nosology, screening and follow-up.

Fibromuscular dysplasia of the brachial artery in patients with spontaneous coronary artery dissection: a case series and literature review.

Spontaneous coronary artery dissection (SCAD) is diagnosed in a very small percentage of patients with suspected acute coronary syndromes who undergo emergency coronary angiography. Although fibromuscular dysplasia (FMD) is known to coexist in patients with SCAD, the vascular sites of FMD and their frequency have not yet been clarified. We retrospectively reviewed the medical records of 16 patients who were diagnosed with and treated for SCAD at our hospital between 1 January 2011 and 31 January 2023. We have summarized their baseline and clinical characteristics and medical variables, including coronary and upper extremity angiography and in-hospital outcomes. One of our patients had concurrent cardiac tamponade requiring pericardial drainage, and another went into hemorrhage shock the following day from dissection of the gastric retroperitoneal artery. Characteristic angiographic features of partial or diffuse nonatherosclerotic stenosis were observed mainly in the distal parts of the coronary arteries or their branches. Notably, in six patients with SCAD who underwent upper extremity angiography, FMD of the brachial artery was revealed. For the first time, to our knowledge, we found a high prevalence of multifocal FMD of the brachial artery in patients with SCAD.

AORTIC INVOLVEMENT IN FIBROMUSCULAR DYSPLASIA: REPORT FROM ARCADIA-POL

Objective: Fibromuscular dysplasia (FMD) affects the walls of medium-sized arteries. There are no described radiological characteristics pathognomonic of aortic FMD but pathological documentation of aortic FMD has been occasionally reported. The aims of this study were to investigate the characteristics of abdominal aorta in patients with FMD versus controls and to review the relevant literature. Design and method: We measured centreline abdominal aortic diameters on 136 patients with FMD (22 with focal disease) enrolled in the ARCADIA-POL study, 60 patients with carotid dissections but no evidence of FMD and 136 healthy controls. Results: The median abdominal aortic diameter did not differ between patients with FMD, patients with carotid dissections and no evidence of FMD and healthy controls. However, aortic diameter at the level of the diaphragm was smaller in patients with focal FMD compared to patients with multifocal FMD, patients with carotid dissections and healthy controls (ANOVA 0.015). Six patients with mid-aortic syndrome (MAS) were reported separately. All had radiological evidence of FMD in medium-sized aortic branches. In one in whom a sample of aortic wall was obtained, histology confirmed focal aortic FMD. A literature review found a further 31 reports of aortic histology with features of FMD. Conclusions: We found no difference in aortic diameters between individuals with or without FMD. Nevertheless, patients with focal FMD had smaller aortic diameters than those with multifocal FMD and controls. This represents another phenotypic difference between multifocal and focal FMD. Focal renal artery stenosis associated with MAS may represent an extreme presentation belonging to the same disease spectrum.

Prevalence and clinical characteristics of renovascular hypertension associated with fibromuscular dysplasia in China.

The aim of this study was to investigate the clinical characteristics of renal artery fibromuscular dysplasia (FMD) in patients in China and identify the cure rate of hypertension after angioplasty. Consecutive hypertensive patients with renal artery stenosis caused by FMD who underwent catheter-based angiography, and were followed at two Chinese referral centres, were retrospectively analysed. All patients underwent a detailed investigation, including demographic characteristics, clinical characteristics, biochemical sampling, Doppler ultrasonography of carotid arteries, magnetic resonance angiography (MRA) of the intracranial artery, and CTA or MRA of the abdominal artery and catheter-based renal angiography. Patients were routinely followed up at 1 month, 6 months and every year after the procedure. Among 245 study participants, with a mean diagnosed age of 26.9 ± 9.9 years, 137 (55.9%) were women, and 38 (15.5%) were children. All patients were diagnosed with hypertension at a mean age of 23.4 ± 8.4 years. There were 73.5% focal and 15.2% multivessel cases. Aneurysms, arterial dissections and total occlusions were found in 21.6, 4.1 and 12.2% of patients, respectively. Patients with multifocal FMD were older (26.0 vs. 23.7 years, P = 0.021) and more often female (70.8 vs. 50.6%, P = 0.004). Among children with renal FMD, 55.2% were men, and 86.8% were focal. After a median follow-up of 7.0 years, multifocal FMD had a higher cure rate of hypertension than focal FMD after revascularization (71.7 vs. 55.8%, P = 0.032). In a cohort of mostly young Chinese patients, the prevalence of hypertension associated with renal FMD is similar in both sexes. Focal FMDs were more frequent than the multifocal ones and, after angioplasty, were associated with a worse blood pressure outcome.

PS-C34-12: MAJOR CLINICAL CHARACTERISTICS OF RENAL ARTERY FIBROMUSCULAR DYSPLASIA IN CHINESE HYPERTENSIVE PATIENTS

Background: Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory vascular disease that most commonly affects renal arteries. There is growing awareness of this disease entity. However, most of the previous studies have been from US or European populations. Methods: Consecutive hypertensive patients with renal artery stenosis caused by FMD underwent catheter-based angiography, followed at two Chinese referral centers in China between January 2000 and December 2021. Results: Of 245 study participants, with a mean diagnosed age of 26.9 ± 9.9 years, 137 (55.9%) were female, 38 (15.5%) were children. All patients had diagnosed hypertension at a mean age of 23.4 ± 8.4 years. 73.5% were focal and 15.2% were multivessel. Aneurysms, arterial dissections, and total occlusions were found in 21.6%, 4.1% and 12.2% of patients, respectively. Patients with multifocal FMD, compared to those with focal FMD, were older (26.0 vs.23.7 years, P = 0.021) and more often female (70.8% vs. 50.6%, P = 0.004), had a higher proportion of renal artery dissection (9.2% vs. 2.2%, P = 0.014), lower proportion of kidney atrophy (18.5% vs.31.1%, P = 0.013), and had fewer antihypertensive drugs (1.7 vs. 2.1, P = 0.002). After a median of 6.9 years follow-up, multifocal FMD had a higher cure rate of hypertension than focal FMD after revascularization (71.2% vs.55.2%, P = 0.033). Conclusions: Chinese patients with renal artery FMD had different characteristics from Caucasians, especially in adults. In Chinese, renal artery FMD occurred primarily in the young hypertensive patients with little sex predilection, and was frequently focal, which showed a worse blood pressure outcome than multifocal.

JS-NG-3: UNIQUE IMAGING FINDINGS IN RENAL ARTERY FIBROMUSCULAR DYSPLASIA

A 35-year-old female patient with fluctuating blood pressure was referred to hypertension department for investigation of possible secondary hypertension. Computed tomographic angiography (CTA) of the renal arteries was performed, demonstrating abnormal right renal artery at the medial portion of the vessel with complete tubular narrowing and right kidney atrophy (right 79*35 mm, left 109*45 mm) (Panel A). Subsequent renal arteriography confirmed the long tubular narrowed right renal artery (Panel C) and the established severe tortuosity collateral vessel from the abdominal aorta (Panel B). The etiological diagnosis of the renal artery stenosis in this young woman was challenging and was supposed to be congenital renal dysplasia. Catheter-based angioplasty was not recommended. However, intravascular ultrasound (IVUS) revealed that it was not congenital narrowed artery, but concentric intimal-medial thickening caused stenosis of the vessel (Panel E). Therefore, renal artery fibromuscular dysplasia (FMD) was diagnosed and considered to be intimal type. Balloon angioplasty was performed, and IVUS showed that the lesion lumen was dilated successfully (Panel F). However, a bailout stent had to be placed because of intimal dissection during angioplasty, and renal blood flow was restored after procedure (Panel D). One month after the procedure, the patient was normotensive without any antihypertensive medication. At 1 year follow-up, the 99mTc-glomerular filtration rate of the right kidney increased from 19.7 to 40.4 ml/min. FMD is a nonatherosclerotic, noninflammatory vascular disease that most commonly affects renal arteries and is recommended to be classified according to angiographic finding as multifocal FMD or focal FMD. Compared with multifocal FMD, focal FMD is less often seen, and the diagnosis of some cases is challenging. In the present case, such a long tubular stenosis of renal artery is rare, and the diagnosis was confirmed by IVUS. IVUS may be a useful tool for the diagnosis of focal FMD.

The urinary proteomic profile of fibromuscular dysplasia.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic, non-inflammatory arterial disease of unclear origin, that may affect virtually all middle-sized arteries, mostly found in young or middle-aged women. More than half of patients have lesions in two or more arterial beds. While many cases are asymptomatic or associated with aspecific symptoms (mild hypertension, migraines, tinnitus), a number of patients develop severe complications such as resistant hypertension, carotid dissection, early stroke or mesenteric ischemia. Two subtypes of FMD have been described: focal and multifocal FMD. Focal FMD, characterized by a focal arterial stenosis of variable length is often difficult to differentiate from localized atherosclerosis, inflammatory or genetic arterial diseases. The hallmark of multifocal FMD, the so-called string of beads, is considered as almost pathognomonic. However, besides classical forms, many patients harbour less typical lesions such as presence of one or two non-circumferential beads, mild irregularities or less regular successive enlargements of arteries. Furthermore, lesions indistinguishable from string of beads are often found in extra-coronary arteries of patients who underwent a spontaneous coronary artery dissection (SCAD), leading some authors to consider SCAD as a form of FMD. Finally, a substantial proportion of patients with FMD harbour arterial aneurysms or dissections, and patients with such complications are sometimes considered to have atypical FMD, even in the absence of a string of beads or focal stenosis. In view of these elements, the development and validation of biomarkers, and particular proteomic biomarkers is of interest to unravel the pathophysiology, to facilitate diagnosis, improve classification and predict complications and evolution of FMD, SCAD and related diseases. Urinary proteomics appears as particularly promising in view of the predominantly renovascular expression of FMD, and of previous identification of proteomic signatures associated with both renal and cardiovascular diseases. In a recent pilot study, we have described a urinary proteomic classifier that allowed distinguishing with high accuracy patients with (mostly renal, multifocal) FMD, both from healthy controls and from patients with chronic kidney diseases and coronary heart disease. This classifier includes mostly collagen-derived peptides, which may suggest increased collagen turnover in affected arteries. The objectives of this presentation are to describe urinary proteomic profile associated with primary FMD, to report preliminary results obtained in patients with SCAD associated with FMD or not, and to discuss the potential consequences of such findings for the understanding, diagnosis and classification of these overlapping entities.

Fibromuscular Dysplasia and Abdominal Aortic Aneurysms Are Dimorphic Sex-Specific Diseases With Shared Complex Genetic Architecture.

The risk of arterial diseases may be elevated among family members of individuals having multifocal fibromuscular dysplasia (FMD). We sought to investigate the risk of arterial diseases in families of individuals with FMD. Family histories for 73 probands with FMD were obtained, which included an analysis of 463 total first-degree relatives focusing on FMD and related arterial disorders. A polygenic risk score for FMD (PRSFMD) was constructed from prior genome-wide association findings of 584 FMD cases and 7139 controls and evaluated for association with an abdominal aortic aneurysm (AAA) in a cohort of 9693 AAA cases and 294 049 controls. A previously published PRSAAA was also assessed among the FMD cases and controls. Of all first degree relatives of probands, 9.3% were diagnosed with FMD, aneurysms, and dissections. Aneurysmal disease occurred in 60.5% of affected relatives and 5.6% of all relatives. Among 227 female first-degree relatives of probands, 4.8% (11) had FMD, representing a relative risk (RR)FMD of 1.5 ([95% CI, 0.75-2.8]; P=0.19) compared with the estimated population prevalence of 3.3%, though not of statistical significance. Of all fathers of FMD probands, 11% had AAAs resulting in a RRAAA of 2.3 ([95% CI, 1.12-4.6]; P=0.014) compared with population estimates. The PRSFMD was found to be associated with an AAA (odds ratio, 1.03 [95% CI, 1.01-1.05]; P=2.6×10-3), and the PRSAAA was found to be associated with FMD (odds ratio, 1.53 [95% CI, 1.2-1.9]; P=9.0×10-5) as well. FMD and AAAs seem to be sex-dimorphic manifestations of a heritable arterial disease with a partially shared complex genetic architecture. Excess risk of having an AAA according to a family history of FMD may justify screening in family members of individuals having FMD.

PLASMA STEROID PROFILE IN WOMEN WITH FIBROMUSCULAR DYSPLASIA - THE ARCADIA-GYN STUDY

Objective: Fibromuscular dysplasia(FMD) mostly affects women in reproductive age. It has been suggested that FMD might be related to female hormone levels or contraceptive use. Therefore, the aim of the ARCADIA-POL substudy ARCADIA-GYN was to perform detailed, prospective obstetrics and gynaecological evaluation of women with FMD. Design and method: We enrolled in the ARCADIA-GYN study 42 women with FMD, ages between 18–46 years old and 45 age-matched healthy, normotensive women who have regular menstruation. By means of LC-MS/MS we analysed plasma steroid profile: estrogen, progesterone, testosterone, aldosterone, cortisol, 18-oxo-cortisol, 18-hydrocortisol, cortisone, 11-deoxycortisol, 21-deoxycortisol, corticosterone, 11-deoxycortisone, progesterone, 17-OH progesterone, pregnenolone, androstenedione, DHEA, DHEA-SO4. Blood samples in all subjects were collected in luteal phase while women stayed without any hormonal contraceptive. FMD was diagnosed based on ARCADIA-POL protocol as published previously. No signs of arterial lesions and/or disturbances in blood flow were found in Doppler duplex evaluations of carotid and renal arteries in control subjects. Results: 42 patients with FMD (34.2 ± 8.1years), predominantly with renal FMD, were compared to 45 healthy, normotensive women (34.0 ± 5.4years; p = 0.88). Hypertension was diagnosed in 88.1% (37) women with FMD. In women with FMD we found lower plasma levels of progesterone (5.1 inter quartile range [IQR] 2.0–8.2 vs 7.6 IQR 3.3–12.5ng/ml;p = 0.017),testosterone (0.20 IQR 0.15–0.28 vs 0.25 IQR 0.18–0.36ng/ml; p = 0.036), DHEA (3.6 IQR 2.6–4.3 vs 4.5 IQR 2.9–6.6ng/ml;p = 0.012), DHEAS04 (1167 IQR 819–1535 vs 1579 IQR 1197–1980ng/ml;p = 0.04) and 11-deoxycortisol (0.09 IQR 0.05–0.12 vs 0.14 IQR 0.09–0.18ng/ml;p = 0.002) as compared to control group. There were no significant differences in other analyzed hormones. There were no differences in steroid profile evaluations between patients with unifocal and multifocal FMD. Conclusions: Women with FMD as compared to healthy controls are characterized by hormonal alterations including lower plasma progesterone level. Taking into consideration previous findings of abnormal balance between estrogen and progesterone receptors in renal artery samples of FMD our results suggest that female hormonal disturbances may have a role in FMD development.

Arterial fibromuscular dysplasia as a factor in sudden cardiac death in young adults

The objective of the study is to consider the problem of diagnostics of a rare vasculopathy, fibromuscular dysplasia of coronary arteries, by the case study of a 19-year-old serviceman, an athlete with sudden death occurred during slight physical exertion. After repeated histological examination as part of the forensic medical examination, the diagnosis was made: «multifocal fibromuscular dysplasia of the coronary arteries and ascending aortic arch, complicated by acute left ventricular failure.» This disease often manifests with the acute coronary syndrome in people of young age. Therefore, special attention was given to the macroscopic and histological features of fibromuscular dysplasia of arteries.

Abstract 14032: Racial Differences in Clinical Manifestations and Events in Fibromuscular Dysplasia: A Report of the United States Registry for FMD

Introduction: Fibromuscular dysplasia (FMD) is a non-inflammatory vasculopathy associated with arterial stenosis, aneurysm, dissection, and tortuosity. We investigated racial differences in clinical manifestations and events of multifocal FMD. Methods: Demographics, medical history, presenting signs and symptoms, and major vascular events were queried from the US Registry for FMD and stratified into White or Black based on self-identified race. Results: Of the 1897 female patients (pts) with multifocal FMD and race reported from 14 sites as of 12/23/2020, there were 1697 (89.5 %) White, 123 (6.5 %) Black, 52 (2.7%) Hispanic, and 25 (1.3%) pts of other races. Given a small number of pts in other groups, analysis was only performed between White and Black pts. Age at diagnosis and at first sign/symptom was similar between the two groups. Black pts were more likely to have a history of hypertension (p=0.009), stroke (p=0.002), and subarachnoid hemorrhage (p<0.001) than White pts. While Black pts were less likely to have had any arterial dissection (p=0.010), a higher percentage had aortic dissection (p=0.015). Family history of FMD was less common among Black pts (p=0.018). There were differences in the distribution of vascular bed involvement and aneurysms between Black and White pts, though not all patients underwent comprehensive vascular imaging. Conclusion: We noted a low number of Black patients enrolled in the US Registry for FMD at FMD specialty centers. There were differences in clinical manifestations, events, and pattern of vascular involvement among Black and White patients enrolled in US Registry, the mechanisms for which require additional study.

FMD and SCAD: Sex-Biased Arterial Diseases With Clinical and Genetic Pleiotropy

Multifocal fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection are both sex-biased diseases disproportionately affecting women over men in a 9:1 ratio. Traditionally known in the context of renovascular hypertension, recent advances in knowledge about FMD have demonstrated that FMD is a systemic arteriopathy presenting as arterial stenosis, aneurysm, and dissection in virtually any arterial bed. FMD is also characterized by major cardiovascular presentations including hypertension, stroke, and myocardial infarction. Similar to FMD, spontaneous coronary artery dissection is associated with a high prevalence of extracoronary vascular abnormalities, including FMD, aneurysm, and extracoronary dissection, and recent studies have also found genetic associations between the two diseases. This review will summarize the relationship between FMD and spontaneous coronary artery dissection with a focus on common clinical associations, histopathologic mechanisms, genetic susceptibilities, and the biology of these diseases. The current status of disease models and critical future research directions will also be addressed.

A Novel Recurrent COL5A1 Genetic Variant Is Associated With a Dysplasia-Associated Arterial Disease Exhibiting Dissections and Fibromuscular Dysplasia.

While rare variants in the COL5A1 gene have been associated with classical Ehlers-Danlos syndrome and rarely with arterial dissections, recurrent variants in COL5A1 underlying a systemic arteriopathy have not been described. Monogenic forms of multifocal fibromuscular dysplasia (mFMD) have not been previously defined. Approach and Results: We studied 4 independent probands with the COL5A1 pathogenic variant c.1540G>A, p.(Gly514Ser) who presented with arterial aneurysms, dissections, tortuosity, and mFMD affecting multiple arteries. Arterial medial fibroplasia and smooth muscle cell disorganization were confirmed histologically. The COL5A1 c.1540G>A variant is predicted to be pathogenic in silico and absent in gnomAD. The c.1540G>A variant is on a shared 160.1 kb haplotype with 0.4% frequency in Europeans. Furthermore, exome sequencing data from a cohort of 264 individuals with mFMD were examined for COL5A1 variants. In this mFMD cohort, COL5A1 c.1540G>A and 6 additional relatively rare COL5A1 variants predicted to be deleterious in silico were identified and were associated with arterial dissections (P=0.005). COL5A1 c.1540G>A is the first recurring variant recognized to be associated with arterial dissections and mFMD. This variant presents with a phenotype reminiscent of vascular Ehlers-Danlos syndrome. A shared haplotype among probands supports the existence of a common founder. Relatively rare COL5A1 genetic variants predicted to be deleterious by in silico analysis were identified in ≈2.7% of mFMD cases, and as they were enriched in patients with arterial dissections, may act as disease modifiers. Molecular testing for COL5A1 should be considered in patients with a phenotype overlapping with vascular Ehlers-Danlos syndrome and mFMD.

Spontaneous Coronary Artery Dissection and Its Association With Fibromuscular Dysplasia and Other Vascular Abnormalities

Fibromuscular dysplasia (FMD) has recently been associated with spontaneous coronary artery dissection (SCAD). We sought to further elucidate the association of FMD with SCAD. We performed a retrospective cohort review of patients with SCAD evaluated at our institution from 2008 to 2019. Baseline characteristics, coronary angiographic data, and screening for FMD were recorded. In patients who completed screening for FMD, variables were compared between patients with FMD and those without. We identified 51 patients with SCAD, all of whom were female, with a mean age of 46.8 years. A quarter of patients underwent percutaneous coronary intervention (PCI) and half of those suffered a complication during PCI. 78% of patients underwent complete screening for FMD, of which 63% were diagnosed with multifocal FMD. Vascular abnormalities other than FMD were found in 70% of screened patients. Patients with FMD were older than those without FMD (50.7 vs 42.6 years, p = 0.006). FMD was more frequently associated with type 2 SCAD (84% vs 47%, p = 0.025), tortuous non-SCAD coronaries (96% vs 53%, p = 0.002), and other vascular abnormalities (84% vs 47%, p = 0.03). In conclusion, the majority of patients within the all-female cohort with SCAD were found to have FMD. Other vascular abnormalities were also common. Patients with FMD were older and were more likely to have type 2 SCAD, tortuous non-SCAD coronary arteries, and other vascular abnormalities.

The Association of Intracranial Aneurysms in Women with Renal Artery Aneurysms

Renal artery aneurysms (RAAs) may reflect a systemic dysplastic arteriopathy, independent of a recognized connective tissue disease. It is hypothesized that RAAs are associated with an increased risk of intracranial aneurysms (IcAs). The objective of this study was to better define the association of IcAs in women with RAAs. Women aged 20 to 60 years who presented with RAAs at the University of Michigan from 2001 to 2016 were included in the study. Their clinical status and radiologic images were retrospectively reviewed, with particular attention directed to the prevalence of IcAs. Phenotypic characteristics predictive of associated cerebrovascular lesions were assessed using various statistical analyses, including binomial logistic regression. Among 83 women with RAAs, the average age at the time of RAA detection was 45.3±9.9 years (range, 20-60years). Hypertension affected 56 (67.5%) patients and poorly controlled hypertension prompted imaging for suspected renal arterial disease in 12 (14.5%) patients. Multifocal fibromuscular dysplasia occurred in 12 (14.8%) of patients, and unifocal stenosis affected 7 (8.4%) patients. Imaging of the intracranial vasculature (n = 31) documented 12 aneurysms in 9 women, with the cavernous internal carotid artery being the most commonly affected artery. Among the study's patients, 20 (24.1%) had an "at-risk disorder for IcA formation," although the frequency of relevant "at-risk disorders" in those with and without IcAs was not statistically different (P=0.21). Rupture risk defined by PHASES score was less than 1% for 10 IcAs, but 2 IcAs carried a 2.4% and 7.2% rupture risk, respectively, over a 5-year time period. Surgical management was pursued in 6 (50%) of the study's IcAs. Coexisting RAAs and IcAs may reflect a systemic arteriopathy. IcAs appear to occur with greater frequency in women with RAAs than the general population. This observation warrants prospective investigation as to the clinical appropriateness and relevance of cerebrovascular imaging in women with RAAs. Furthermore, this study's findings prompt further investigation of the underlying pathogenesis of what appears to be a broader and more complex arterial disease than previously recognized.

Spontaneous Bilateral Carotid Artery Dissection Revealing Multifocal Fibromuscular Dysplasia

Background: Fibromuscular dysplasia (FMD) is a rare idiopathic segmental non-arteriosclerotic and non-inflammatory arterial disease of small to medium-sized vessels. Although it is considered a benign entity, FMD can lead to potentially severe cerebrovascular complications. We present an atypical clinical case of ischemic stroke (IS) caused by bilateral carotid dissection revealing multifocal FMD. Case Report: A 43-year-old right-handed female with no medical history suddenly developed somnolence with left-sided weakness. Clinical examination revealed left hemiplegia and left central facial paralysis with an NIHSS score: 22. Cerebral tomography (CT) with arterial angiogram revealed abilateralis of the middle cerebral arteries (MCA), a double dissection of the internal carotids (IC), aneurysmal ectasia of the left IC, and aneurysm of the M2 segment of the MCA. Brain magnetic resonance imaging (MRI) with arterial angiography confirmed the bilateral dissection. A cerebral angiography (CA) revealed a radiological pattern of multifocal FMD. The angiography of the aorta and its branches showed adiffuse dysplasia of the renal arteries. The patient was put under antiaggregants. The modified Rankin score (mRS) after three months was three. Conclusion: Cerebrovascular FMD has typical angiographic features, the “string of beads” appearance being the most common. Although the risk of a stroke in patients with cervical FMD is low, it can lead to a severe stroke and the long-term risks are unknown. Patient registries should be encouraged to better understand the mechanisms and evolutionary profile of FMD and alert clinicians to this potentially disabling condition.

Differences in renal hemodynamics and renin secretion between patients with unifocal and multifocal fibromuscular dysplasia.

Fibromuscular dysplasia (FMD) can be classified in a multifocal and a unifocal subtype. As unifocal FMD generally leads to more severe hypertension at younger age, we hypothesized that renal hemodynamics are more disturbed in unifocal renal artery FMD as compared with multifocal FMD, leading to increased renin secretion. We measured renal blood flow (Xenon washout method), renin secretion, and glomerular filtration rate per kidney in 101 patients with FMD (26 unifocal and 75 multifocal), all off medication and prior to balloon angioplasty. We found that renal blood flow and glomerular filtration were substantially lower in kidneys with unifocal FMD as compared with multifocal FMD. In the affected kidney from patients with unilateral FMD for example, mean renal blood flow was 173 ± 77 in unifocal vs. 244 ± 79 ml/100 g kidney/min in multifocal FMD (P = 0.013). Moreover, lateralization in renin secretion was only observed in a subset of patients with unifocal FMD, but not in any of the patients with multifocal FMD. These findings suggest that the impact of unifocal FMD lesions on the kidney is more severe, resulting in a classical pattern of renovascular hypertension. In multifocal FMD, however, renal blood flow is more preserved, local renin secretion is not increased, and the association between renin levels and blood pressure is inverse. These differences may explain the often more severe clinical presentation and higher success rate of revascularization in unifocal FMD, but also suggest that the pathophysiological mechanisms leading to hypertension may differ between these two disease entities.

ESH-ENDORSED EUROPEAN/INTERNATIONAL FIBROMUSCULAR DYSPLASIA REGISTRY

Objective: The pioneering works of French and United States research teams have changed our conception of Fibromuscular Dysplasia (FMD) from a rare cause of renal artery stenosis in young women to a more frequent, often systemic vascular disease, which can be diagnosed at all ages, both in men and women. We report here the main characteristics of the first 609 patients enrolled in the European/International FMD registry endorsed by the ESH. Design and method: The current analysis was performed in 609 patients enrolled from November 2015 to January 2018 in 30 centres from 17 countries also including 3 extra-European countries (Argentina, Japan and Tunisia). Results: Enrolled patients were predominantly women (83%) and Caucasians (88%). Age at diagnosis was 45.8 ± 15.8 years, 74% of patients were hypertensive, 72% had a multifocal FMD and 31% multivessel FMD. Family history of FMD was reported in 2.7% of cases. Compared to patients with multifocal FMD, patients with focal FMD were younger (39.2 ± 15.9 vs. 48.4 ± 14.9 years, p = 0.003), more often male (26% vs. 13%, p = 0.0002), had less often multivessel FMD (12% vs. 39%, p = 0.0001) and more frequent revascularization interventions (70% vs. 50%, p = 0.01). Compared to patients with single-vessel FMD, patients with multivessel FMD were older (49.5 ± 14.2 vs. 44.1 ± 16.1 years, p = 0.03), had lower eGFR (84.2 ± 28.1 vs. 94.4 ± 40.6 mL/min, p = 0.0005) and were more frequently of the multifocal subtype (89% vs. 64%, p = 0.00001). Notably, the proportion of arterial dissections was higher in men than in women (12% vs. 2%, p = 0.01). Conclusions: The main findings of the European/International FMD registry are in line with those of the French-Belgian ARCADIA study and the United States registry, with the exception of a lower proportion of multivessel FMD, which probably reflects a lack of systematic vascular exploration in some centres. In the near future, the European/International FMD registry will make possible further comparisons between old and young, incident and prevalent patients, and/or patients from different ethnicities or regions of the world. Accumulation of follow-up data may also provide insights on predictive factors of progression/complication.

Echocardiographic assessment of left ventricular morphology and function in patients with fibromuscular dysplasia: the ARCADIA-POL study.

To provide a comprehensive assessment of left ventricle (LV) structure, and function and to detect alterations in cardiac properties in relationship to presence, subtypes and extent of fibromuscular dysplasia (FMD). We studied 144 patients with FMD. The control group consisted of 50 matched individuals. Office and ambulatory blood pressure levels were evaluated. Echocardiography was employed to assess: left ventricular mass index (LVMI), systolic function including speckle tracking echocardiography and diastolic function assessed by mitral flow and tissue Doppler imaging. There were no differences in LV morphology and function between patients with FMD and the control group. Among 128 patients with renal FMD, there were no differences in LVMI and LV systolic function between patients with unifocal and multifocal FMD. The patients with multifocal FMD were characterized by lower early diastolic velocity (e') as compared with unifocal FMD and control groups. However, in a multivariate regression model, e' was not independently correlated with FMD. There were no associations between echocardiographic indexes and vascular involvement of FMD. Also, there were no differences in LV morphology and function in patients with significant renal artery stenosis (RAS) compared with patients with history of significant RAS and patients with nonsignificant RAS. Our study in contrast to those with atherosclerotic RAS, did not show differences in LV morphology and function between FMD patients and matched controls. Although FMD can result in hypertension and serious vascular complications, there is no proof that it can alter LV regardless of FMD type and its extent.