JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY VOL. 68, NO. 2, 2016 ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION ISSN 0735-1097/$36.00 PUBLISHED BY ELSEVIER http://dx.doi.org/10.1016/j.jacc.2016.04.044 Dissection and Aneurysm in Patients With Fibromuscular Dysplasia Findings From the U.S. Registry for FMD Daniella Kadian-Dodov, MD,a Heather L. Gornik, MD, MHS,b Xiaokui Gu, MA,c James Froehlich, MD, MPH,c J. Michael Bacharach, MD, MPH,d Yung-Wei Chi, DO,e Bruce H. Gray, DO,f Michael R. Jaff, DO,g Esther S.H. Kim, MD, MPH,b Pamela Mace, RN,h Aditya Sharma, MBBS,i Eva Kline-Rogers, MS, RN, NP,b Christopher White, MD,j Jeffrey W. Olin, DOa ABSTRACT BACKGROUND Fibromuscular dysplasia (FMD) is a noninflammatory arterial disease that predominantly affects women. The arterial manifestations may include beading, stenosis, aneurysm, dissection, or tortuosity. OBJECTIVES This study compared the frequency, location, and outcomes of FMD patients with aneurysm and/or dissection to those of patients without. METHODS The U.S. Registry for FMD involves 12 clinical centers. This analysis included clinical history, diagnostic, and therapeutic procedure results for 921 FMD patients enrolled in the registry as of October 17, 2014. RESULTS Aneurysm occurred in 200 patients (21.7%) and dissection in 237 patients (25.7%); in total, 384 patients (41.7%) had an aneurysm and/or a dissection by the time of FMD diagnosis. The extracranial carotid, renal, and intra- cranial arteries were the most common sites of aneurysm; dissection most often occurred in the extracranial carotid, vertebral, renal, and coronary arteries. FMD patients with dissection were younger at presentation (48.4 vs. 53.5 years of age, respectively; p < 0.0001) and experienced more neurological symptoms and other end-organ ischemic events than those without dissection. One-third of aneurysm patients (63 of 200) underwent therapeutic intervention for aneurysm repair. CONCLUSIONS Patients with FMD have a high prevalence of aneurysm and/or dissection prior to or at the time of FMD diagnosis. Patients with dissection were more likely to experience ischemic events, and a significant number of patients with dissection or aneurysm underwent therapeutic procedures for these vascular events. Because of the high prevalence and associated morbidity in patients with FMD who have an aneurysm and/or dissection, it is recommended that every patient with FMD undergo one-time cross-sectional imaging from head to pelvis with computed tomographic angiog- raphy or magnetic resonance angiography. (J Am Coll Cardiol 2016;68:176–85) © 2016 by the American College of Cardiology Foundation. From the aZena and Michael A. Wiener Cardiovascular Institute and Marie-Joseé and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York; bVascular Medicine Section, Department of Cardiovascular Medicine, Cleveland Clinic Heart and Vascular Institute, Cleveland, Ohio; cCardiovascular Center, University of Michigan, Ann Arbor, Michigan; dDepartment of Cardiology, Avera Heart Hospital of South Dakota, Sioux Falls, South Dakota; eDivision of Cardiovascular Medicine, University of California Davis Medical Center, Sacremento, California; fVascular Health Alliance, Greenville, South Carolina; gFireman Vascular Center, Massachusetts General Hospital, Boston, Massachusetts; hFibromuscular Listen to this manuscript’s Dysplasia Society of America, Rocky River, Ohio; iDivision of Cardiovascular Medicine, University of Virginia, Charlottesville, audio summary by Virginia; and the jDepartment of Cardiovascular Diseases, John Ochsner Heart and Vascular Institute, Ochsner Medical Center, JACC Editor-in-Chief University of Queensland Ochsner Clinical School, New Orleans, Louisiana. The U.S. Registry for Fibromuscular Dysplasia (FMD) is Dr. Valentin Fuster. supported by the FMD Society of America (FMDSA). Dr. Gornik is an FMDSA Medical Advisory Board member. Dr. Froehlich is a consultant for Pfizer, Merck, Novartis, Janssen, and Boehringer-Ingelheim. Ms. Mace is FMDSA Executive Board Director. Dr. Olin is FMDSA Medical Advisory Board Chair. Dr. Jaff is a VIVA Physicians and Society for Cardiovascular Angiography and Inter- vention board member. Dr. Kim is consultant for Philips Ultrasound. All other authors have reported that they have no re- lationships relevant to the contents of this paper to disclose. Mark Creager, MD, served as Guest Editor for this paper. Manuscript received February 1, 2016; revised manuscript received April 5, 2016, accepted April 6, 2016. JACC VOL. 68, NO. 2, 2016 Kadian-Dodov et al. 177 JULY 12, 2016:176– 85 Dissection and Aneurysm in Patients With FMD ibromuscular dysplasia (FMD) is a noninflam- string-of-beads type is now called “multi- ABBREVIATIONS F matory arterial disease that affects predomi- focal” FMD (3,4) (Figure 1A), whereas “focal” AND ACRONYMS nantly women. Arterial manifestations FMD denotes a single area of concentric or CTA = computed tomographic include beading, stenosis, aneurysm, dissection, and tubular stenosis, most commonly due to angiography arterial tortuosity (Central Illustration) (1,2).The intimal fibroplasia, pathologically (Figure 1B) FMD = fibromuscular dysplasia most common histological type of FMD is medial (3,5,6). MRA = magnetic resonance fibroplasia, which results in an artery with a “string SEE PAGE 186 angiography of beads” appearance, representing alternating areas SAH = subarachnoid of stenosis due to fibrous webs and post-stenotic dila- The prevalence of FMD remains unknown; hemorrhage tion. Due to the increasing use of endovascular ther- however, data from asymptomatic kidney SCAD = spontaneous coronary apy, tissue samples are rarely obtained in the donors suggest that up to 4% of the general artery dissection current era; thus, it has been recommended that an population may have FMD (1,7).Prevalence TIA = transient ischemic attack angiographic classification scheme replace the previ- may be even higher in patients with resistant hyper- ously used histopathological classification (3,4).The tension (8). FMD affects predominantly women 20 to CENTRAL ILLUSTRATION The Many Faces of Fibromuscular Dysplasia Kadian-Dodov, D. et al. J Am Coll Cardiol. 2016;68(2):176–85. Imaging characteristics of FMD include a “string of beads” appearance to the artery, a focal area of stenosis, extreme tortuosity, dissection of a coronary or peripheral artery, and/or aneurysm of a peripheral artery, an intracranial artery, or the aorta. 3D ¼ 3-dimensional; FMD ¼ fibromuscular dysplasia. 178 Kadian-Dodov et al. JACC VOL. 68, NO. 2, 2016 Dissection and Aneurysm in Patients With FMD JULY 12, 2016:176– 85 FIGURE 1 Multifocal and Focal FMD Catheter-based angiography shows (A) multifocal FMD involving the right renal artery branches (arrow) and (B) focal FMD (arrow) involving the right renal artery. FMD ¼ fibromuscular dysplasia. 60 years of age, although men and patients of all ages Intracranial FMD most often manifests as aneurysm, can be affected (4,9).IntheU.S.RegistryforFMD, with an estimated prevalence of approximately 7%, 93.5% of patients are women (9).Diseasemanifesta- which is higher than the 2% to 5% rate reported in the tions depend on the arterial bed involved: most often general population (24,25).InFMDpatientswhohave the extracranial carotid or vertebral arteries are developed subarachnoid hemorrhage (SAH) (7,9),es- associated with headache (generally migraine-type), timates of cerebral aneurysm prevalence may be as pulsatile tinnitus, transient ischemic attack (TIA), or high as 50% (26,27). Despite a clear association, there stroke, whereas the renal arteries are often associated is a poor understanding of the prevalence and clinical with hypertension (1,4,7,9,10). Asymptomatic FMD presentation of aneurysm in patients with FMD, as may occur in some patients, although again, the fre- well as long-term prognosis for these events. In quency is unknown. Savard et al. (6) showed there addition to intracranial aneurysms, FMD is a predis- wasanaveragedelayof4yearsfromtheonsetof posing factor in the development of renal artery an- hypertension until diagnosis in patients with focal eurysms (28,29) and aneurysms in other vascular FMD and 9 years in patients with multifocal FMD. A beds. similar delay of 4.1 years to diagnosis was reported in The goal of the U.S. Registry for FMD is to increase the registry (9). understanding of the epidemiology, clinical charac- Dissection may result in devastating outcomes teristics, management, and outcomes of patients for the typically young and otherwise healthy FMD with FMD. The objective of this report was to define patient. Spontaneous carotid or vertebral artery the prevalence of aneurysm and dissection in this dissection accounts for approximately 20% of cohort of FMD patients and better understand the strokes in patients #45 years of age (11),andspon- associated clinical phenotypes and outcomes of these taneous coronary artery dissection (SCAD) has patients. been reported to account for 24% of myocardial infarctions (MI) in women #50 years of age (12–14). METHODS Multiple studies have demonstrated an increased prevalence of FMD in patients who experience The U.S. Registry for FMD was started in 2008, and carotid or vertebral artery dissection (15% to 20%), details of its management have been described pre- coronary artery dissection (45% to 86%) (11,14–19),or viously (9). Since publication of the first report renal artery dissection (20). It is not uncommon for involving 447 patients, an additional