Differentiating between segmental arterial mediolysis and other arterial vasculopathies to establish an early diagnosis - a systematic literature review and proposal of new diagnostic criteria.

Segmental arterial mediolysis (SAM) is a rare vascular disease, characterized by acute but transient vulnerability of the wall of medium-sized arteries. The most characteristic feature of SAM is its biphasic course: an injurious phase marked by acute weakness of the arterial wall leading to acute dissection and/or hemorrhage, followed by a reparative phase in which granulation tissue and fibrosis restore the injured arterial wall. Residual stenosis, aneurysms, and/or arterial wall irregularities may remain visible on future imaging studies. Differentiating between SAM and other arterial vasculopathies is difficult due to its similarities with many other vascular diseases, such as vasculitis, fibromuscular dysplasia, inherited connective tissue disorders, and isolated visceral artery dissection. In this systematic review, we provide an overview on SAM, with an emphasis on the differential diagnosis and diagnostic work-up. We propose new diagnostic criteria to help establish a prompt diagnosis of SAM, illustrated by case examples from our multidisciplinary vascular clinic.

Thyroid and adrenal incidentalomas on chest CT: Prevalence, diagnostic work-up and outcomes in a cohort of COVID-19 suspected patients.

OBJECTIVE: Due to increased use of computed tomography (CT), prevalence of thyroid and adrenal incidentalomas is rising. Yet, previous studies on the outcomes of diagnostic work-up of incidentalomas are subjected to inclusion bias. Therefore, we aimed to investigate prevalence and outcomes of diagnostic work-up of thyroid and adrenal incidentalomas detected on chest CT in a less selected population of COVID-19 suspected patients. DESIGN: A retrospective, observational cohort study. METHODS: We included all COVID-19 suspected patients who underwent chest CT between March 2020 and March 2021. Radiology reports and medical records were reviewed for the presence and subsequent diagnostic work-up of thyroid and adrenal incidentalomas. RESULTS: A total of 1,992 consecutive COVID-19 patients were included (59.4% male, median age 71 years [IQR: 71-80]). Thyroid and adrenal incidentalomas were identified in 95 (4.8%) and 133 (6.7%) patients, respectively. Higher prevalence was observed with increasing age, among female patients and in patients with malignancy. Forty-four incidentalomas were further analyzed, but no malignancies were found. Only three lesions were hormonally active (1 thyrotoxicosis and 2 mild autonomous cortisol secretion). Diagnostic work-up did not lead to any change in clinical management in 97.7% of the analyzed patients. CONCLUSION: Prevalence rates of thyroid and adrenal incidentalomas on chest CT in a less selected COVID-19 cohort were 4.8% and 6.7%, respectively. Yet, as all incidentalomas turned out to be benign and only three lesions were (mildly) hormonally active, this raises the question whether intensive diagnostic work-up of incidentalomas is necessary in all patients.

Current progress in clinical, molecular, and genetic aspects of adult fibromuscular dysplasia.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease that may involve medium-sized muscular arteries throughout the body. The majority of FMD patients are women. Although a variety of genetic, mechanical, and hormonal factors play a role in the pathogenesis of FMD, overall, its cause remains poorly understood. It is probable that the pathogenesis of FMD is linked to a combination of genetic and environmental factors. Extensive studies have correlated the arterial lesions of FMD to histopathological findings of arterial fibrosis, cellular hyperplasia, and distortion of the abnormal architecture of the arterial wall. More recently, the vascular phenotype of lesions associated with FMD has been expanded to include arterial aneurysms, dissections, and tortuosity. However, in the absence of a string-of-beads or focal stenosis, these lesions do not suffice to establish the diagnosis. While FMD most commonly involves renal and cerebrovascular arteries, involvement of most arteries throughout the body has been reported. Increasing evidence highlights that FMD is a systemic arterial disease and that subclinical alterations can be found in non-affected arterial segments. Recent significant progress in FMD-related research has led to improve our understanding of the disease's clinical manifestations, natural history, epidemiology, and genetics. Ongoing work continues to focus on FMD genetics and proteomics, physiological effects of FMD on cardiovascular structure and function, and novel imaging modalities and blood-based biomarkers that can be used to identify subclinical FMD. It is also hoped that the next decade will bring the development of multi-centred and potentially international clinical trials to provide comparative effectiveness data to inform the optimal management of patients with FMD.

Renal artery fibromuscular dysplasia and its effect on the kidney.

Fibromuscular dysplasia is a heterogeneous group of systemic, noninflammatory, and nonatherosclerotic diseases of the vascular wall. It is the second-most common abnormality of the renal artery. Although hypertension is the most common presenting symptom, other symptoms, such as pulsatile tinnitus, stroke, chest pain, or abdominal discomfort, may result from other affected vascular beds. Revascularization of the renal artery appears to be effective at lowering blood pressure in many patients with renal artery fibromuscular dysplasia. For a long time, the intrarenal pathophysiological changes and mechanisms leading to hypertension had hardly been studied in patients with renal artery fibromuscular dysplasia. Recent data, however, has provided more insight into the effects of renal artery fibromuscular dysplasia on the intrarenal microvasculature and the intra-renal renin-angiotensin system in these patients. Moreover, these data have changed our view of the pathophysiological mechanisms leading to hypertension in patients with renal artery fibromuscular dysplasia. In this review, we will discuss recent clinical and scientific developments regarding renal artery fibromuscular dysplasia with an emphasis on its effects on the kidney.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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 ±â€Š77 in unifocal vs. 244 ±â€Š79 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. CONCLUSION: 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.

Coronary Tortuosity: A Clue to the Diagnosis of Fibromuscular Dysplasia?

BACKGROUND: Fibromuscular dysplasia (FMD) is a systemic, nonatherosclerotic, noninflammatory vasculopathy that is often overlooked by clinicians. Clinical clues could help in selecting patients for further evaluation for the presence of FMD. Recently, it was observed that tortuosity of the coronary arteries is often present in patients with FMD-related abnormalities of the coronary artery. Therefore, we wondered if the presence of coronary tortuosity might provide a clinical clue to the diagnosis of extracoronary FMD. CASES: We describe 5 cases of FMD in whom diagnostic studies for FMD were initiated because of the presence of coronary tortuosity. FMD was found in all 5 patients in the renal and/or cervical arteries. CONCLUSIONS: Our 5 cases suggest that exertional chest pain in the presence of coronary tortuosity may be helpful in selecting patients for further evaluation for the presence of FMD. Further research should focus on the prevalence of FMD among patients with coronary tortuosity and whether the presence of additional clinical clues (such as the presence of hypertension at young age or pulsatile tinnitus) next to coronary tortuosity can predict the risk for FMD in individual patients.

Pathophysiological differences between multifocal fibromuscular dysplasia and atherosclerotic renal artery stenosis.

BACKGROUND: Fibromuscular dysplasia (FMD) and atherosclerotic renal artery stenosis (ARAS) are the most common causes of renovascular hypertension. So far, FMD is believed to cause hypertension via similar mechanisms as in ARAS, that is, a decrease in renal blood flow, which subsequently leads to increased renin secretion. However, given the differences in the blood pressure (BP)-lowering effect of revascularization between patients with ARAS and FMD, we questioned whether this is true. METHODS: We measured renal blood flow (Xenon washout method) and renin secretion per kidney and their relationship to BP in a cohort of 64 patients with multifocal FMD and 110 patients with ARAS (off medication, prior to revascularization). RESULTS: We found that renal blood flow is significantly higher in FMD as compared with ARAS. In patients with unilateral ARAS, renin secretion was increased in the affected kidney as compared with the unaffected kidney. This lateralization in renin secretion, however, was not found in unilateral FMD. After correction for differences in baseline characteristics, we found that systemic renin levels and local renin secretion was lower in FMD as compared with ARAS. Moreover, the relationship between BP and renin secretion in FMD was inverse to that in ARAS. CONCLUSION: These findings argue against the hypothesis that FMD induces hypertension via similar pathophysiological mechanism as in ARAS.

Renal hemodynamics and renin-angiotensin system activity in humans with multifocal renal artery fibromuscular dysplasia.

BACKGROUND: Fibromuscular dysplasia (FMD) is the second most common cause of renovascular hypertension. Nonetheless, knowledge on the renal microvasculature and renin-angiotensin system (RAS) activity in kidneys with FMD is scarce. Given the fairly good results of revascularization, we hypothesized that the renal microvasculature and RAS are relatively spared in kidneys with FMD. METHOD: In 58 hypertensive patients with multifocal renal artery FMD (off medication) and 116 matched controls with essential hypertension, we measured renal blood flow (Xenon washout method) per kidney and drew blood samples from the aorta and both renal veins to determine renin secretion and glomerular filtration rate per kidney. RESULTS: We found that renal blood flow and glomerular filtration rate in FMD were comparable to those in controls. Although systemic renin levels were somewhat higher in FMD, renal renin secretion was not elevated. Moreover, in patients with unilateral FMD, no differences between the affected and unaffected kidney were observed with regard to renal blood flow, glomerular filtration rate, or renin secretion. In men, renin levels and renin secretion were higher as compared with women. The renal blood flow response to RAS modulation (by intrarenal infusion of angiotensin II, angiotensin-(1-7), an angiotensin II type 1 receptor blocker, or a nitric oxide synthase blocker) was also comparable between FMD and controls. CONCLUSION: Renal blood flow, glomerular filtration, and the response to vasoactive substances in kidneys with multifocal FMD are comparable to patients with essential hypertension, suggesting that microvascular function is relatively spared. Renin secretion was not increased and the response to RAS modulation was not affected in kidneys with FMD.

Angiotensin-(1-7) as a strategy in the treatment of hypertension?

PURPOSE OF REVIEW: The renin-angiotensin system plays an important role in cardiovascular disease via the production of angiotensin II. Over the past decades, however, more and more evidence has accumulated suggesting an important role for another angiotensin: Angiotensin-(1-7) [Ang-(1-7)]. In this review, we discuss the recent findings on the effects of Ang-(1-7) and the angiotensin-converting enzyme2/Ang-(1-7)/Mas axis on the cardiovascular system. RECENT FINDINGS: Recent studies demonstrated that Ang-(1-7) exerts a vasodilatory and antiproliferative effect via stimulation of the Mas receptor and inhibition of the effects of angiotensin-type 1 receptor stimulation by angiotensin II. This results in a dynamic equilibrium between Ang-(1-7) and angiotensin II. Various animal studies have demonstrated that Ang-(1-7) has beneficial effects on blood pressure, kidney function, and the prevention of cardiovascular disease. Although targeting the angiotensin-converting enzyme 2/Ang-(1-7)/Mas axis has been difficult so far, several new therapeutic strategies are being developed. Promising results of these new strategies on blood pressure and cardiovascular disease were demonstrated in animal studies. SUMMARY: The beneficial effects of the angiotensin-converting enzyme2/Ang-(1-7)/Mas axis have been widely demonstrated in animal studies and provide a promising basis for further development of drugs targeting this axis of the renin-angiotensin system. Further research in humans, however, is necessary to make a serious step forward. VIDEO ABSTRACT: http://links.lww.com/CONH/A8.