2024-01-15 15:34:41
Arteriopathies
Published on January 15, 2024Read 8 min
François SILHOL, Competence Center for Rare Vascular Diseases PACA Arterial Hypertension Unit, Timone University Hospital, Marseille
Fibromuscular dysplasia (FMD) is a diffuse pathology of medium-sized arteries, with a high female/male ratio of 9/1. This affection can be expressed in different modes of expression. Only the pearl necklace appearance allows the diagnosis to be made. It can also be expressed in the form of a dissection, an aneurysm or arterial tortuosity, but these latter forms are not pathognomonic, as they exist in other arterial pathologies. There is a rarer unifocal form that is more often seen in young patients.
Presentation of DFM DFM can affect all arteries, but it preferentially affects the renal arteries, the intra- and extra-cranial carotid arteries, the vertebral arteries, but also the visceral arteries and the arteries of the limbs. It presents variously in the form of stenosis, aneurysm, dissection or occlusion of the arteries. These multiple forms explain the different initial clinical expressions of the disease leading to its diagnosis, ranging from simple tinnitus to arterial dissection and of course arterial hypertension (hypertension). It is important to understand precisely the nature of DFM to correctly understand its management and anticipate its evolution. The first doctors to describe DFM did it on an angiogram. It is a characteristic image where we see a succession of piles of plates forming a necklace of pearls, but it only reflects part of reality. Angiography (figure 1) being a subtraction image, it only reflects part of the nature of DFM. We see neither the irregular hyperplasia of the wall generating spasms nor the intravascular diaphragms. Figure 1. Angiogram of a multifocal FMD of the right renal artery. This artistic representation (figure 2) shows how a DFM is traditionally represented: wall hyperplasia and irregularities. The artistic representation that we see here has the merit of exposing the 3 modes of expression of DFM: pearl necklace, aneurysm and arterial dissection. In our minds, it is this string of pearls appearance that is primarily responsible for the stenosis. But this is partly incorrect, because here too an essential element is missing which will allow us to understand the difficulty of quantitatively evaluating this disease. These are the intravascular diaphragms visible, sometimes on Doppler ultrasound. They are essentially what cause turbulence and hemodynamically significant stenoses. Figure 2. Artistic representation of multifocal dysplasia and its 3 modes of expression: string of pearls, aneurysm and arterial dissection. Thus during endovascular revascularization the objective is to rupture these diaphragms and not to dilate the hyperplastic wall. If the balloon is too large in diameter, there is a risk of causing dissection. Also, the use of a stent (apart from a dissection-type complication) should be avoided, because the hyperplasia wall tends to spasm and lead to restenosis. This propensity for spasm is quite noticeable on intravascular ultrasound (figures 3 to 5). Figure 3. IVUS endovascular ultrasound appearance of renal artery dysplasia (F. Silhol, JL Bonnet). Succession of hyperplasia and atrophy of the media with very spastic behavior of the artery during the passage of the endovascular probe. Figure 4. Ultrasound of a renal artery showing irregular wall hyperplasia and intravascular diaphragms. Figure 5. Histological appearance of fibromuscular dysplasia. Histological section from the series F. Silhol, B. Chetaille collected by P. Piquet, CHU Timone, Marseille. Photomicroscopic histological section of medial dysplasia (Leica DMD 108 digital photomicroscope): fibrous hypertrophy, rupture of the internal elastic border. There is a variable thickness of the media, sometimes hypertrophied in certain areas. Some smooth muscle cells are replaced by extracellular matrix. In other areas, atrophy or disappearance of the media is observed, allowing the development of aneurysms or dissections. Smooth muscle cells appear globally disorganized in space. Evaluation of dysplastic stenosis of the renal arteries Most often, for a cardiologist, the diagnosis of DFM is considered in the face of hypertension in a woman. The first step will be to make the diagnosis. If you are in the office with an ultrasound machine, you can use the following criteria. Qualitative echo-Doppler criteria – Appearance of strung color/energy beads (figure 6); – irregular thickening of the vascular wall; – intravascular diaphragms: comb sign; – irregular variations in Doppler velocities: acoustic rasp. Figure 6. Medial dysplasia of the right renal artery. Specific Doppler settings in directional energy Doppler allowing the anatomy of the artery and the pearl necklace appearance to be appreciated (F. Silhol). The quantitative evaluation is more delicate: the very nature of the DFM, the presence of staged stenoses, the technical difficulty of the examination can be obstacles. However, currently it is the combination of an in-depth Doppler examination confirmed by an angiographic pressure gradient performed during revascularization which is the best “couple” to determine the tight or loose nature of the DFM. Studies are underway to better exploit CT angiography in the quantification of stenosis. What is certain is that the Doppler ultrasound criteria for atheromatous stenosis of the renal arteries are not at all suitable for the evaluation of FMD. In the recently published DYSART study, we determined angiographic pressure criteria as well as Doppler ultrasound criteria (PSV > 300 cm/s, reno/aortic ratio > 3.2) as velocity thresholds for hemodynamically significant stenoses. In patients selected by clinical indicators and Doppler ultrasound, the decrease in the translesional systolic gradient ≤ 10 mmHg or reduced by at least 80% following angioplasty, is correlated with a significantly high success rate of PTA in hypertension secondary to multifocal fibrodysplastic stenosis at 7 months. Renal dysplasia can sometimes present in a very complex manner; identifying the tightest portion of the artery is important for the interventional radiologist. We carry out a Doppler ultrasound identification, with measurement of the tightest zone of the dysplasia and its location in relation to the ostium of the artery (figure 7). Figure 7. Ultrasound identification before angioplasty. The tightest area of right renal artery dysplasia is 37 mm from the ostium. Note the specific ultrasound setting with PRF at 77 cm/s, the gain at 53%, the high filters (F. Silhol). Of course, other criteria are taken into consideration before revascularization such as ambulatory blood pressure, history of the disease, renal function, etc. Recourse to a specialized ESH center, a competence center for dysplasias, is currently easy in France and practitioners can request additional advice in case of doubt. Diffusion of the disease DFM is a diffuse disease, its diagnosis on an arterial segment must lead to the search for another location on the arterial territories. In our center we perform a systematic arterial body scan. Research among collaterals DFM can also be familial, this concerns a little more than 10% of DFMs. Epidemiological evidence from families with FMD supports a genetic origin. In our series, the presence of DFM was diagnosed in approximately 20% of first-degree collaterals. In the literature, the prevalence of vascular damage in families of patients with FMD (apart from only cases of familial FMD) is very high in first and second degree collaterals. There is a family history of stroke (more than 50%), aneurysms in more than 20% of collaterals and sudden deaths in almost 20% while the diagnosis of FMD in another member of the family does not It is established that in 7% of cases. These figures underline on the one hand the severity of the disease and on the other hand the probable diagnostic under-evaluation of the disease in FMD families and the general population. There is no consensus regarding the search for dysplasia in asymptomatic territory. In our center, when a DFM of the renal arteries is discovered, we systematically perform a cerebral CT angiogram with evaluation of the supra-aortic trunks and intracranial arteries as well as a search for dysplasia of the abdominal aortic branches and visceral arteries. and iliac arteries. Dysplasia is a progressive disease, but weakly. In our cohort, although the arterial site most affected by DFM lesions is the renal arteries, cerebrovascular events represent the main complication at the time of diagnosis (15, 7% of patients and 31.4% of total complications) or during follow-up (4.3% of patients and 40% of total complications). These are mainly ischemic strokes, whether they are constituted (CVA) or not (TIA); respectively 16 (11.4%) and 2 (1.4%). At the time of diagnosis, 50% of patients had presented a major complication compared to only 10.7% during follow-up: optimal management allows the risks of major complications to be avoided; the majority of these neurological events: stroke and TIA. The latest European recommendations summarize the evolution of DFM management well (figure 8). Figure 8. Fibromuscular dysplasia is the focus of significant research Single nucleotide polymorphism in the PHACTR1 gene common to DFM, spontaneous cervical artery dissection (CeAD), and coronary artery dissection (SCAD). Recurrent variant of the COL5A1 gene associated with a phenotype encompassing multifocal DFM, dissections, aneurysms and arterial tortuosities. Involvement of the TGF-β signaling pathway has been suggested. Platelet-derived growth factor (PDGF encoded by the PDGFRB gene). Proteomics Research DFM involves changes in arterial wall composition: DEFINE-FMD study is a functional multi-omics systems biology study aimed at deciphering the molecular and genetic basis of DFM (Olin et al.). CD2-associated protein = CD2AP associated with risk of having DFM (P = 0.0003) highly expressed in lysophosphatidylcholine (lysoPC) endothelial cells. DFM biomarkers: we have demonstrated the presence of a biomarker, the A2B adenosine receptors present in patients with DFM compared to a control population: this might allow a biological diagnosis of DFM (figure 9 ). Figure 9. For patients, the “pearl necklace” association will be launched in early 2024 and will inform patients, encourage discussion and help them manage this disease. IN PRACTICE • Fibromuscular dysplasia is a rare vascular disease whose etiology, evaluation and prognosis are progressing with new developments in clinical research. • The practitioner’s objective will be to screen patients, specify the severity and prognosis of their lesions, explore their families and ensure follow-up in collaboration with specialized centers. • This will allow, through the national register and prospective studies, to improve the care and prognosis of patients and their families.
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