Fibromuscular dysplasia: Advances in understanding and management

A BROADER SCOPE OF ARTERIAL MANIFESTATIONS

Since FMD was first described in the 1930s,³⁴ most case reports have focused on its renal artery manifestations. In 1964, extrarenal involvement was first reported, which included carotid, iliac, and visceral arteries.³⁵ The medical community has since recognized that the disease can affect medium-sized vessels throughout the body and, more recently, that it is a multifaceted disease with varying arterial manifestations outside of the typical string-of-beads appearance or focal FMD lesions.¹ In addition to multifocal or focal narrowings, arterial manifestations of FMD include arterial tortuosity, aneurysm, and dissection.

Arterial tortuosity

Tortuosity or redundancy of the arteries, particularly the internal carotid arteries, has recently been reported in association with FMD.⁶ A study based on vascular ultrasonography findings identified this anatomic variant (described as having the appearance of an S-curvature of the internal carotid artery) in 31.9% (37 of 116) of FMD patients.⁶ This rate of tortuosity is higher than that in the general population, especially when compared with patients of similar age (under age 70). Arterial tortuosity is a common finding in FMD and may be seen in other arterial segments (Figure 2).

Aneurysm and dissection

Both arterial aneurysm and arterial dissection are recognized as manifestations of FMD. A US Registry report published in 2016 found a high prevalence of aneurysm and dissection in the FMD population.⁷ Of the 921 patients included in this analysis, 21.6% had an aneurysm, 25.7% had an arterial dissection, and 41.7% had either aneurysm or dissection. The most common locations for aneurysm were the extracranial carotid, renal, and intracranial arteries, whereas dissection commonly occurred in the extracranial carotid, vertebral, renal, and coronary arteries. The authors noted that these data may be an underestimation, because the entire cohort did not undergo comprehensive screening for asymptomatic aneurysm or dissection. Patients with aneurysm were more likely to have a history of smoking and subarachnoid hemorrhage, while those with dissection were younger and more likely to have headache, neck pain, and end-organ ischemia, including stroke, renal infarction, or myocardial infarction.

FMD of the coronary arteries

The association between FMD and spontaneous coronary artery dissection (SCAD) has recently been discovered (Figure 3). SCAD typically presents as troponin-positive acute coronary syndrome.³⁶ FMD has been identified as a predisposing condition for SCAD in two case series from Vancouver General Hospital³⁷ and Mayo Clinic.³⁸ The case series from Mayo Clinic found that 45% of SCAD patients had FMD in the extracoronary vessels; the case series from Vancouver General Hospital found that 72% had FMD. A more recent study found that there seems to be other manifestations of FMD in the coronary arteries aside from SCAD.³⁹ In this series, 32 patients with multifocal FMD (in the renal, external iliac, or cerebrovascular arteries) who underwent coronary angiography for suspected symptomatic coronary artery disease (either acute coronary syndrome or stable angina) were found to have coronary artery lesions different from those of atherosclerotic disease. In addition to coronary lesions of dissection (SCAD), the most common findings were marked coronary arterial tortuosity (the “S curve”), followed by areas of atypical-appearing irregular or smooth stenosis. More than half of patients in the series had segments of coronary artery ectasia (enlargement).

APPROACH TO MANAGEMENT

There is no cure for FMD, and thus management strategies focus on thorough evaluation and surveillance, lifestyle modification, and treatment of symptoms. Vascular procedures, such as angioplasty or treatment of aneurysms, are required for some patients. Because patients with FMD present with a diverse set of symptoms, consultation with a specialist who has experience with FMD and who works closely with an interdisciplinary team of experts is recommended.¹ The interdisciplinary FMD care team may include a vascular medicine physician, cardiologist, nephrologist, neurologist, neurosurgeon, vascular surgeon, and vascular interventionalist (interventional cardiologist and radiologist).

Imaging and screening the vasculature in FMD patients

Because of the variability in location and manifestations of FMD and the high prevalence of aneurysm and dissection, all patients should undergo comprehensive one-time head-to-pelvis screening during the workup for FMD.^1,7 Although the technical standard of diagnostic imaging is catheter angiography, noninvasive imaging—computed tomographic angiography (CTA), magnetic resonance angiography (MRA), duplex ultrasonography—is more commonly used to diagnose and monitor the disease.

A study from our group at Cleveland Clinic assessed the utility of a specialized CTA protocol of the chest, abdomen, and pelvis to image and diagnose manifestations of FMD outside of the cerebrovasculature.⁴⁰ Incremental findings on imaging included areas of beading or focal narrowing in a new vascular territory and previously undiagnosed arterial aneurysm or dissection. These findings were seen in a variety of vascular beds, including the renal, iliac, and mesenteric arteries, although aortic abnormalities were rare. This study supports the diagnostic value of CTA for FMD to detect asymptomatic aneurysms and areas of arterial dissection, but it also suggests that routine vascular imaging of the thorax may not be necessary.⁴⁰ In cases of SCAD, on-table renal and iliac angiography (performed after coronary angiography) can assist in diagnosis of FMD as an underlying cause.³⁶ The cerebrovascular arteries (carotid, vertebral, and intracranial vessels) can be imaged later with noninvasive imaging (CTA, MRA).

As a general strategy, once patients with FMD undergo comprehensive imaging, a surveillance program is customized for the patient based on the anatomic location of the disease and the nature of the imaging findings. For example, renal and internal carotid artery FMD may be followed with annual duplex ultrasonography, whereas cerebral and renal or visceral aneurysms require periodic CTA or MRA.

Medical therapies

The medical regimen for patients with FMD varies based on disease location and symptoms, though there are no definitive treatment guidelines because of limited data. A study from the US Registry found that 72.9% of registrants were treated with antiplatelet medications,¹¹ and this is a standard approach in our clinical practice for prevention of thromboembolic events. Antiplatelet drug therapy was more common in elderly patients, patients with a history of coronary artery disease or vascular intervention for FMD, and patients with isolated cerebrovascular FMD.¹¹ Blood pressure management is also important in the medical therapy of patients with FMD who have hypertension. For patients with renal artery involvement, treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker has been suggested.¹

Vascular intervention

The need for vascular intervention (eg, angioplasty or endovascular or surgical aneurysm treatment) is determined primarily by symptoms, with renal artery angioplasty for hypertension the most common FMD-related procedure. It is uncommon for vascular intervention to be performed for cerebrovascular FMD in the absence of recurrent transient ischemic attack or stroke despite antiplatelet therapy, arterial dissection that has failed medical management, or sizable aneurysm that requires treatment to prevent rupture.

When considering intervention for renal artery FMD, it is important to note that the appearance of multifocal FMD (beading) on angiography or noninvasive imaging does not reflect the hemodynamic severity of disease: translesional pressure gradients should be measured across the affected artery to determine if there is actually hemodynamic stenosis caused by an area of beading and to select patients for balloon angioplasty.¹ Repeat pressure gradient assessment is done after angioplasty to confirm hemodynamic success.¹ Surgical intervention for renal FMD is uncommon. It is generally reserved for complex cases in which endovascular techniques have failed.¹ 

Asymptomatic patients with cerebral, visceral, or arterial aneurysm may require endovascular or surgical treatment. If surgery is indicated, the treatment approach (coiling, stenting, or open surgery) is determined by the size and location of the aneurysm, patient-related factors that may influence the risk of rupture (eg, uncontrolled hypertension, family history of ruptured aneurysm), the anatomic characteristics of the aneurysm, and the feasibility of endovascular vs open surgical repair. A US Registry study of 200 patients with an aneurysm reported that 31.5% underwent intervention to treat the aneurysm.⁷ Aneurysms requiring intervention were most commonly noted in the extracranial carotid, renal, and intracranial arteries.⁷ 

CONCLUSION

Awareness and understanding of FMD have substantially improved in recent years, and this has translated into better care for many patients with FMD. Important advancements have included the recognition of the variability of manifestations of this disease—ranging from an arterial string-of-beads appearance to aneurysm, dissection, and tortuosity—and establishing the need for comprehensive vascular imaging screening in FMD patients. Establishing the association of FMD with SCAD has led to better care for patients with SCAD and presents the opportunity to optimize management of these patients to prevent further vascular events. Research initiatives and heightened awareness have provided valuable insight into this disease, but further work is needed to determine the causal mechanisms of FMD and to continue to develop better management strategies.