Dissection and Aneurysm in Patients With Fibromuscular Dysplasia

Findings From the U.S. Registry for FMD

Daniella Kadian-Dodov, MD; Heather L. Gornik, MD, MHS; Xiaokui Gu, MA; James Froehlich, MD, MPH; J. Michael Bacharach, MD, MPH; Yung-Wei Chi, DO; Bruce H. Gray, DO; Michael R. Jaff, DO; Esther S.H. Kim, MD, MPH; Pamela Mace, RN; Aditya Sharma, MBBS; Eva Kline-Rogers, MS, RN, NP; Christopher White, MD; Jeffrey W. Olin, DO

Disclosures

J Am Coll Cardiol. 2016;68(2):176-185. 

In This Article

Abstract and Introduction

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 intracranial 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 angiography or magnetic resonance angiography.

Introduction

Fibromuscular dysplasia (FMD) is a noninflammatory arterial disease that affects predominantly women. Arterial manifestations include beading, stenosis, aneurysm, dissection, and arterial tortuosity (Central Illustration).[1,2] The most common histological type of FMD is medial fibroplasia, which results in an artery with a "string of beads" appearance, representing alternating areas of stenosis due to fibrous webs and post-stenotic dilation. Due to the increasing use of endovascular therapy, tissue samples are rarely obtained in the current era; thus, it has been recommended that an angiographic classification scheme replace the previously used histopathological classification.[3,4] The string-of-beads type is now called "multifocal" FMD[3,4] (Figure 1A), whereas "focal" FMD denotes a single area of concentric or tubular stenosis, most commonly due to intimal fibroplasia, pathologically (Figure 1B).[3,5,6]

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 = fibromuscular dysplasia.

The prevalence of FMD remains unknown; however, data from asymptomatic kidney donors suggest that up to 4% of the general population may have FMD.[1,7] Prevalence may be even higher in patients with resistant hypertension.[8] FMD affects predominantly women 20 to 60 years of age, although men and patients of all ages can be affected.[4,9] In the U.S. Registry for FMD, 93.5% of patients are women.[9] Disease manifestations depend on the arterial bed involved: most often the extracranial carotid or vertebral arteries are associated with headache (generally migraine-type), pulsatile tinnitus, transient ischemic attack (TIA), or stroke, whereas the renal arteries are often associated with hypertension.[1,4,7,9,10] Asymptomatic FMD may occur in some patients, although again, the frequency is unknown. Savard et al.[6] showed there was an average delay of 4 years from the onset of hypertension until diagnosis in patients with focal FMD and 9 years in patients with multifocal FMD. A similar delay of 4.1 years to diagnosis was reported in the registry.[9]

Dissection may result in devastating outcomes for the typically young and otherwise healthy FMD patient. Spontaneous carotid or vertebral artery dissection accounts for approximately 20% of strokes in patients ≤45 years of age,[11] and spontaneous coronary artery dissection (SCAD) has been reported to account for 24% of myocardial infarctions (MI) in women ≤50 years of age.[12–14] Multiple studies have demonstrated an increased prevalence of FMD in patients who experience carotid or vertebral artery dissection (15% to 20%), coronary artery dissection (45% to 86%),[11,14–19] or renal artery dissection.[20] It is not uncommon for FMD patients to have dissections in more than 1 artery.[19,21–23]

While small aneurysms are likely to be asymptomatic, a ruptured aneurysm, especially if intracranial, may result in a disabling stroke or death. Intracranial FMD most often manifests as aneurysm, with an estimated prevalence of approximately 7%, which is higher than the 2% to 5% rate reported in the general population.[24,25] In FMD patients who have developed subarachnoid hemorrhage (SAH),[7,9] estimates of cerebral aneurysm prevalence may be as high as 50%.[26,27] Despite a clear association, there is a poor understanding of the prevalence and clinical presentation of aneurysm in patients with FMD, as well as long-term prognosis for these events. In addition to intracranial aneurysms, FMD is a predisposing factor in the development of renal artery aneurysms[28,29] and aneurysms in other vascular beds.

The goal of the U.S. Registry for FMD is to increase understanding of the epidemiology, clinical characteristics, management, and outcomes of patients with FMD. The objective of this report was to define the prevalence of aneurysm and dissection in this cohort of FMD patients and better understand the associated clinical phenotypes and outcomes of these patients.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....