Focal Fibromuscular Dysplasia Research Articles

A Rare Case of Focal Renal Fibromuscular Dysplasia Treated With Angioplasty: A Case Report.

Fibromuscular dysplasia is an idiopathic, segmental, nonatherosclerotic, noninflammatory vascular disease that can lead to arterial stenosis, tortuosity, occlusion, aneurysms, and dissection. Fibromuscular dysplasia is a rare cause of hypertension that can easily be missed. To date, there has been no definitive treatment for fibromuscular dysplasia. In this report, we present an uncommon case of renovascular hypertension in a 21-year-old non-white female with a 3-year history of hypertension secondary to fibromuscular dysplasia involving bilateral renal arteries. Computed tomography angiography during the arterial phase revealed distal focal narrowing of the right main renal artery, distal focal narrowing of the left main renal artery, and proximal focal narrowing of the left accessory lower renal artery. Percutaneous balloon dilatation of the stenotic lesion was performed successfully up to 1year After the procedure, the arterial blood pressure was within the normal range (110/70 to 125/75mmHg) without medication. After 1year of follow-up, CTA revealed re-stenosis in left main renal artery without clinical symptoms and normal blood pressure. Repeated procedure was done successfully. This case report highlights the difficulty in the diagnosis and treatment of focal fibromuscular dysplasia in young non-white female patients. Computerized tomographic angiography is a useful tool for identifying the cause and showing the benefit of percutaneous transluminal renal angioplasty treatment for this rare entity, as an early percutaneous angioplasty intervention may have a clinical cure for hypertension.

AORTIC INVOLVEMENT IN FIBROMUSCULAR DYSPLASIA: REPORT FROM ARCADIA-POL

Objective: Fibromuscular dysplasia (FMD) affects the walls of medium-sized arteries. There are no described radiological characteristics pathognomonic of aortic FMD but pathological documentation of aortic FMD has been occasionally reported. The aims of this study were to investigate the characteristics of abdominal aorta in patients with FMD versus controls and to review the relevant literature. Design and method: We measured centreline abdominal aortic diameters on 136 patients with FMD (22 with focal disease) enrolled in the ARCADIA-POL study, 60 patients with carotid dissections but no evidence of FMD and 136 healthy controls. Results: The median abdominal aortic diameter did not differ between patients with FMD, patients with carotid dissections and no evidence of FMD and healthy controls. However, aortic diameter at the level of the diaphragm was smaller in patients with focal FMD compared to patients with multifocal FMD, patients with carotid dissections and healthy controls (ANOVA 0.015). Six patients with mid-aortic syndrome (MAS) were reported separately. All had radiological evidence of FMD in medium-sized aortic branches. In one in whom a sample of aortic wall was obtained, histology confirmed focal aortic FMD. A literature review found a further 31 reports of aortic histology with features of FMD. Conclusions: We found no difference in aortic diameters between individuals with or without FMD. Nevertheless, patients with focal FMD had smaller aortic diameters than those with multifocal FMD and controls. This represents another phenotypic difference between multifocal and focal FMD. Focal renal artery stenosis associated with MAS may represent an extreme presentation belonging to the same disease spectrum.

O063 Should the presence of a carotid web be an indication for carotid intervention? A 12-year single centre retrospective study

Abstract Introduction Carotid webs are a rare form of focal fibromuscular dysplasia and a possible cause of ischaemic stroke. They are defined as an abnormal shelf-like projection of intimal fibrous tissue into the carotid bulb. We reviewed patients found to have carotid webs at our unit over a 12-year period. Methods Radiology reports of all cross-sectional imaging from 2010-2021 were searched for the phrase carotid web. Images were reviewed to confirm the finding. Patients with previous carotid intervention were excluded. Electronic patient records were reviewed to establish presenting symptoms, diagnosis, management and stroke recurrence. Results 60 patients with carotid webs were identified. Ages ranged from 36-92 years. The gender ratio was 31 male:29 female. 29 patients had left-sided carotid webs, 22 right-sided and 9 bilateral. No patients had a pre-event diagnosis of fibromuscular dysplasia. 27 patients had an ischaemic intracerebral event - 18 in the territory relevant to the web location and nine in other territories. 1 patient was treated with thrombolysis, 1 with thrombectomy and 1 with thrombolysis and thrombectomy. None underwent carotid intervention. Of the 18 patients with a carotid web on the ipsilateral side to their ischaemic event, none had a repeat event recorded. Conclusion 30% of patients had an ischaemic event corresponding to the territory supplied by a carotid artery with a web. Current management of carotid webs favours conservative management with antiplatelet therapy. However, these data suggest carotid intervention should be considered in selected patients where stroke symptoms correlate to the laterality of the carotid web.

Transient ischemic attack due to dynamic evolution of carotid artery web.

Carotid artery web (CaW) is a rare focal fibromuscular dysplasia, which is an underappreciated risk factor for transient ischemic attack. This case illustrates the dynamic evolution of secondary thrombus and plaque in CaW, and the importance of carotid doppler ultrasound in early detection and follow-up.

Prevalence and clinical characteristics of renovascular hypertension associated with fibromuscular dysplasia in China.

The aim of this study was to investigate the clinical characteristics of renal artery fibromuscular dysplasia (FMD) in patients in China and identify the cure rate of hypertension after angioplasty. Consecutive hypertensive patients with renal artery stenosis caused by FMD who underwent catheter-based angiography, and were followed at two Chinese referral centres, were retrospectively analysed. All patients underwent a detailed investigation, including demographic characteristics, clinical characteristics, biochemical sampling, Doppler ultrasonography of carotid arteries, magnetic resonance angiography (MRA) of the intracranial artery, and CTA or MRA of the abdominal artery and catheter-based renal angiography. Patients were routinely followed up at 1 month, 6 months and every year after the procedure. Among 245 study participants, with a mean diagnosed age of 26.9 ± 9.9 years, 137 (55.9%) were women, and 38 (15.5%) were children. All patients were diagnosed with hypertension at a mean age of 23.4 ± 8.4 years. There were 73.5% focal and 15.2% multivessel cases. Aneurysms, arterial dissections and total occlusions were found in 21.6, 4.1 and 12.2% of patients, respectively. Patients with multifocal FMD were older (26.0 vs. 23.7 years, P = 0.021) and more often female (70.8 vs. 50.6%, P = 0.004). Among children with renal FMD, 55.2% were men, and 86.8% were focal. After a median follow-up of 7.0 years, multifocal FMD had a higher cure rate of hypertension than focal FMD after revascularization (71.7 vs. 55.8%, P = 0.032). In a cohort of mostly young Chinese patients, the prevalence of hypertension associated with renal FMD is similar in both sexes. Focal FMDs were more frequent than the multifocal ones and, after angioplasty, were associated with a worse blood pressure outcome.

PS-C34-12: MAJOR CLINICAL CHARACTERISTICS OF RENAL ARTERY FIBROMUSCULAR DYSPLASIA IN CHINESE HYPERTENSIVE PATIENTS

Background: Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory vascular disease that most commonly affects renal arteries. There is growing awareness of this disease entity. However, most of the previous studies have been from US or European populations. Methods: Consecutive hypertensive patients with renal artery stenosis caused by FMD underwent catheter-based angiography, followed at two Chinese referral centers in China between January 2000 and December 2021. Results: Of 245 study participants, with a mean diagnosed age of 26.9 ± 9.9 years, 137 (55.9%) were female, 38 (15.5%) were children. All patients had diagnosed hypertension at a mean age of 23.4 ± 8.4 years. 73.5% were focal and 15.2% were multivessel. Aneurysms, arterial dissections, and total occlusions were found in 21.6%, 4.1% and 12.2% of patients, respectively. Patients with multifocal FMD, compared to those with focal FMD, were older (26.0 vs.23.7 years, P = 0.021) and more often female (70.8% vs. 50.6%, P = 0.004), had a higher proportion of renal artery dissection (9.2% vs. 2.2%, P = 0.014), lower proportion of kidney atrophy (18.5% vs.31.1%, P = 0.013), and had fewer antihypertensive drugs (1.7 vs. 2.1, P = 0.002). After a median of 6.9 years follow-up, multifocal FMD had a higher cure rate of hypertension than focal FMD after revascularization (71.2% vs.55.2%, P = 0.033). Conclusions: Chinese patients with renal artery FMD had different characteristics from Caucasians, especially in adults. In Chinese, renal artery FMD occurred primarily in the young hypertensive patients with little sex predilection, and was frequently focal, which showed a worse blood pressure outcome than multifocal.

JS-NG-3: UNIQUE IMAGING FINDINGS IN RENAL ARTERY FIBROMUSCULAR DYSPLASIA

A 35-year-old female patient with fluctuating blood pressure was referred to hypertension department for investigation of possible secondary hypertension. Computed tomographic angiography (CTA) of the renal arteries was performed, demonstrating abnormal right renal artery at the medial portion of the vessel with complete tubular narrowing and right kidney atrophy (right 79*35 mm, left 109*45 mm) (Panel A). Subsequent renal arteriography confirmed the long tubular narrowed right renal artery (Panel C) and the established severe tortuosity collateral vessel from the abdominal aorta (Panel B). The etiological diagnosis of the renal artery stenosis in this young woman was challenging and was supposed to be congenital renal dysplasia. Catheter-based angioplasty was not recommended. However, intravascular ultrasound (IVUS) revealed that it was not congenital narrowed artery, but concentric intimal-medial thickening caused stenosis of the vessel (Panel E). Therefore, renal artery fibromuscular dysplasia (FMD) was diagnosed and considered to be intimal type. Balloon angioplasty was performed, and IVUS showed that the lesion lumen was dilated successfully (Panel F). However, a bailout stent had to be placed because of intimal dissection during angioplasty, and renal blood flow was restored after procedure (Panel D). One month after the procedure, the patient was normotensive without any antihypertensive medication. At 1 year follow-up, the 99mTc-glomerular filtration rate of the right kidney increased from 19.7 to 40.4 ml/min. FMD is a nonatherosclerotic, noninflammatory vascular disease that most commonly affects renal arteries and is recommended to be classified according to angiographic finding as multifocal FMD or focal FMD. Compared with multifocal FMD, focal FMD is less often seen, and the diagnosis of some cases is challenging. In the present case, such a long tubular stenosis of renal artery is rare, and the diagnosis was confirmed by IVUS. IVUS may be a useful tool for the diagnosis of focal FMD.

The urinary proteomic profile of fibromuscular dysplasia.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic, non-inflammatory arterial disease of unclear origin, that may affect virtually all middle-sized arteries, mostly found in young or middle-aged women. More than half of patients have lesions in two or more arterial beds. While many cases are asymptomatic or associated with aspecific symptoms (mild hypertension, migraines, tinnitus), a number of patients develop severe complications such as resistant hypertension, carotid dissection, early stroke or mesenteric ischemia. Two subtypes of FMD have been described: focal and multifocal FMD. Focal FMD, characterized by a focal arterial stenosis of variable length is often difficult to differentiate from localized atherosclerosis, inflammatory or genetic arterial diseases. The hallmark of multifocal FMD, the so-called string of beads, is considered as almost pathognomonic. However, besides classical forms, many patients harbour less typical lesions such as presence of one or two non-circumferential beads, mild irregularities or less regular successive enlargements of arteries. Furthermore, lesions indistinguishable from string of beads are often found in extra-coronary arteries of patients who underwent a spontaneous coronary artery dissection (SCAD), leading some authors to consider SCAD as a form of FMD. Finally, a substantial proportion of patients with FMD harbour arterial aneurysms or dissections, and patients with such complications are sometimes considered to have atypical FMD, even in the absence of a string of beads or focal stenosis. In view of these elements, the development and validation of biomarkers, and particular proteomic biomarkers is of interest to unravel the pathophysiology, to facilitate diagnosis, improve classification and predict complications and evolution of FMD, SCAD and related diseases. Urinary proteomics appears as particularly promising in view of the predominantly renovascular expression of FMD, and of previous identification of proteomic signatures associated with both renal and cardiovascular diseases. In a recent pilot study, we have described a urinary proteomic classifier that allowed distinguishing with high accuracy patients with (mostly renal, multifocal) FMD, both from healthy controls and from patients with chronic kidney diseases and coronary heart disease. This classifier includes mostly collagen-derived peptides, which may suggest increased collagen turnover in affected arteries. The objectives of this presentation are to describe urinary proteomic profile associated with primary FMD, to report preliminary results obtained in patients with SCAD associated with FMD or not, and to discuss the potential consequences of such findings for the understanding, diagnosis and classification of these overlapping entities.

Percutaneous cutting balloon angioplasty for the treatment of renovascular hypertension in children and adolescents.

Percutaneous transluminal renal angioplasty (PTRA), the recommended treatment in children with renovascular hypertension (RVH), often has unsatisfactory outcomes. Cutting balloons may improve the results of angioplasty in different vascular beds with complex and resistant lesions. We retrospectively analysed the effects of percutaneous cutting balloon angioplasty (PCBA) on blood pressure, cardiac mass and renal artery acceleration time in children/adolescents referred to our centre for RVH. Thirteen patients (aged 9-19 years) with renal artery stenosis (RAS) and severe hypertension were identified. RASs were focal fibromuscular (FMD) or FMD-like dysplasia (in six cases bilateral, in five associated with mid aortic syndrome). Ten patients had uncontrolled hypertension, in nine cases associated with left ventricular hypertrophy (LVH). Acceleration time was abnormal in all stenotic arteries. Eighteen PCBA were performed, in three arteries associated with stent implantation. PCBA was technically successful in all individuals without major complications. In one patient, an intra-stent restenosis occurred, successfully redilated with conventional angioplasty without recurrence at 4 years distance. One year after PCBA, mean SBP and DBPs were markedly reduced from 146 ± 25 to 121 ± 10 mmHg and from 87 ± 11 to 65 ± 12 mmHg, respectively ( P < 0.001 for both). At that time, hypertension was cured in seven children and controlled in five individuals. This favourable outcome was confirmed with ambulatory blood pressure measurement in four patients. At the latest follow-up, left ventricular mass and acceleration time were normal in all patients. PCBA proved to be a well tolerated and effective procedure that can be considered as an alternative to PTRA to treat hypertensive children/adolescents with recurrent or resistant RAS.

A Systematic Literature Review of Patients With Carotid Web and Acute Ischemic Stroke.

Background and Purpose- Carotid web (CW) is a rare form of focal fibromuscular dysplasia defined as an abnormal shelf-like projection of intimal fibrous tissue into the carotid bulb. It is theorized that CW leads to ischemic stroke secondary to blood flow stasis and subsequent embolization. The natural history and optimal management of CW are unclear. To address this knowledge gap, we performed a systematic literature review (SLR) of CW. Methods- Our librarians performed a SLR for CW and related terminology. Patient-level demographics, stroke risk factors, neuroimaging findings, stroke recurrence or stroke free-duration, and treatment modality were extracted. We used descriptive statistics to characterize our results. When specific patient-level metrics were not reported, the denominators for reporting percentage calculations were adjusted accordingly. Results- Our literature search produced 1150 articles. Thirty-seven articles including 158 patients (median age 46 years [range 16-85], 68% women, 76% symptomatic) met entry criteria and were included in our SLR. Of the symptomatic CW patients: 57% did not have stroke risk factors, 56% who received medical therapy had recurrent stroke (median 12 months, range 0-97), and 72% were ultimately treated with carotid revascularization (50% carotid stenting, 50% carotid endarterectomy). There were no periprocedural complications or recurrent strokes in carotid revascularization patients. Conclusions- CW leads to ischemic stroke in younger patients without conventional stroke risk factors. We found a high stroke recurrence rate in medically managed symptomatic CW patients, whereas carotid revascularization effectively prevented recurrent stroke. Our findings should be interpreted with caution because of risk of publication and reporting bias.

ESH-ENDORSED EUROPEAN/INTERNATIONAL FIBROMUSCULAR DYSPLASIA REGISTRY

Objective: The pioneering works of French and United States research teams have changed our conception of Fibromuscular Dysplasia (FMD) from a rare cause of renal artery stenosis in young women to a more frequent, often systemic vascular disease, which can be diagnosed at all ages, both in men and women. We report here the main characteristics of the first 609 patients enrolled in the European/International FMD registry endorsed by the ESH. Design and method: The current analysis was performed in 609 patients enrolled from November 2015 to January 2018 in 30 centres from 17 countries also including 3 extra-European countries (Argentina, Japan and Tunisia). Results: Enrolled patients were predominantly women (83%) and Caucasians (88%). Age at diagnosis was 45.8 ± 15.8 years, 74% of patients were hypertensive, 72% had a multifocal FMD and 31% multivessel FMD. Family history of FMD was reported in 2.7% of cases. Compared to patients with multifocal FMD, patients with focal FMD were younger (39.2 ± 15.9 vs. 48.4 ± 14.9 years, p = 0.003), more often male (26% vs. 13%, p = 0.0002), had less often multivessel FMD (12% vs. 39%, p = 0.0001) and more frequent revascularization interventions (70% vs. 50%, p = 0.01). Compared to patients with single-vessel FMD, patients with multivessel FMD were older (49.5 ± 14.2 vs. 44.1 ± 16.1 years, p = 0.03), had lower eGFR (84.2 ± 28.1 vs. 94.4 ± 40.6 mL/min, p = 0.0005) and were more frequently of the multifocal subtype (89% vs. 64%, p = 0.00001). Notably, the proportion of arterial dissections was higher in men than in women (12% vs. 2%, p = 0.01). Conclusions: The main findings of the European/International FMD registry are in line with those of the French-Belgian ARCADIA study and the United States registry, with the exception of a lower proportion of multivessel FMD, which probably reflects a lack of systematic vascular exploration in some centres. In the near future, the European/International FMD registry will make possible further comparisons between old and young, incident and prevalent patients, and/or patients from different ethnicities or regions of the world. Accumulation of follow-up data may also provide insights on predictive factors of progression/complication.

Abstract 207: A Systematic Literature Review of Patients with Carotid Web and Acute Ischemic Stroke

Introduction: Carotid Web (CW) is a rare form of focal fibromuscular dysplasia that results in an abnormal shelf-like projection of intimal fibrous tissue into the carotid bulb. It is theorized that CW leads to ischemic stroke secondary to blood flow stasis and subsequent embolization. There is uncertainty in diagnosis, prognosis, and optimal management of this uncommon entity. To address this knowledge gap, we performed a systematic literature review (SLR) of CW. Methods: Our literature search for CW and related terms yielded 1017 results. After a preliminary assessment of all 1017 retrieved manuscripts; 72 manuscripts were reviewed in detail. A total of 31 manuscripts met entry criteria and were included in our SLR. We present the demographics, cardiovascular (CV) risk factors, neuroimaging findings, stroke recurrence or stroke free-duration, and treatment modality of CW patients. Results: Our SLR resulted in 104 patients with CW, (median age at presentation: 45.7 [IQR 45-57], 52.3% female). The majority (68.3%) of CW patients did not have CV risk factors, however, 22.2% of patients were smokers. 47.8% of patients suffered recurrent stroke. The majority of patients were ultimately treated with antiplatelet therapy (94.4%) and 21.2% underwent carotid revascularization (4.8% carotid stenting, 16.3% carotid endarterectomy). None of the patients who underwent revascularization had a reported stroke recurrence. See Table. Conclusions: CW is a rare disease leading to ischemic stroke in younger patients without typical CV risk factors. CW patients in our SLR were at extremely high risk for recurrent stroke (47.8%). Aggressive secondary stroke prevention measures are indicated in this patient population, however, the optimal treatment strategies remain unclear. Carotid revascularization may be the definitive treatment for certain patients with CW, but further studies are needed as incomplete reporting and potential publication bias limit our findings.

Dysplasie fibromusculaire des artères rénales

Fibromuscular dysplasia is non-atherosclerotic, non-inflammatory disease of the medium caliber arteries causing segmental stenosis, and sometimes aneurysm and/or dissection. Renal involvement is either asymptomatic or revealed by hypertension, rarely acute complications (renal infarction/hemorrhage). Cross-sectional imaging or angiography differentiates multifocal fibromuscular dysplasia (pearl necklace appearance) and focal fibromuscular dysplasia (tubular stenosis). Several differential diagnoses are to be mentioned. Carotid and vertebral involvement are possible. Smoking cessation must be encouraged. Selected patients benefit from renal revascularization. The best indications are recent or resistant hypertension, and progressive renal atrophy. Angioplasty without stent revascularization is the technique of choice in purely stenotic forms.

Clinical management of renal artery fibromuscular dysplasia: temporal trends and outcomes.

Renal artery fibromuscular dysplasia (FMD) is a heterogeneous condition with a broad and evolving phenotypic and angiographic spectrum. We documented therapeutic management in patients with renal artery FMD, by analyzing the medical records of hypertensive patients diagnosed with FMD at a single referral center from 1986 to 2012. Characteristics at presentation, treatments and outcomes were compared between patients diagnosed with FMD before and after the year 2000. Characteristics at presentation and outcomes were compared between patients managed conservatively, by angioplasty or surgery. Patients seen since 2000 (n = 278) were older, had lower blood pressure (BP) levels and were more often managed conservatively than those diagnosed before 2000 (n = 134). Revascularized patients had more often focal FMD and were more often men, diagnosed with hypertension and FMD at a younger age, had higher BP levels and a higher prevalence of renal asymmetry or infarction than patients treated conservatively. At the most recent visit, BP was below 140/90 mmHg in two-thirds of the patients, in all treatment groups. Multifocal FMD was managed conservatively in 60% of the cases (older patients, less severe hypertension) with similar BP outcome compared to revascularization, even after adjustment for potential confounding factors. The trends towards the diagnosis of FMD in older patients with less severe hypertension underscore the need for a careful selection of patients who might benefit from revascularization. This is especially true for multifocal FMD, which might be adequately managed by medication in a substantial number of cases.

The toxic oil syndrome.

Hundreds died and thousands were poisoned by rapeseed oil adulterated with aniline and sold illegally in Spain in 1981. The clinical manifestations, now known as the toxic oil syndrome, include pulmonary hypertension and right ventricular hypertrophy plus widespread vascular and neural lesions in other organs. Many of the late deaths ended with a scleroderma-like illness. Because scleroderma involves the heart, an examination was made of the small and large coronary arteries, the neural structures, and the conduction system from 11 victims dying with the toxic oil syndrome. Dense fibrosis, atrionodal junctional hemorrhages, and cystic degeneration of the sinus nodes were present. Small and large coronary arteries exhibited focal fibromuscular dysplasia and a proliferative cystic myointimal degeneration. This latter abnormality was associated with sloughing of the inner wall and embolization of the detached fragment downstream in the same coronary artery. Every heart had many degenerative lesions within nerves, ganglia, and the coronary chemoreceptor. Based upon observations by others with experimental feeding of rapeseed oil containing either high or low erucic acid, it is suggested that this oil must remain a major suspected cause of the toxic oil syndrome, particularly in conjunction with some as yet unexplained facilitative influence by oleoanilids. If this is so, it is important to reexamine the widely recommended use of any rapeseed oil product as a suitable food for humans or animals.

Normal and abnormal consequences of apoptosis in the human heart. From postnatal morphogenesis to paroxysmal arrhythmias.

Apoptosis and necrosis are two distinctly different forms of cell death, and both occur in the human heart. In contrast to necrosis, apoptosis is not associated with inflammation for two reasons. First, the apoptotic cell does not swell or rupture before it is engulfed by either a macrophage or even a neighboring like cell. Second, the phagocytosis occurs with unusual rapidity. Apoptosis, also thought of as cell suicide, is a tidy way of removing cells no longer useful, in essence a form of selective deletion. These features make apoptosis a valuable component of morphogenesis, mediation of hormonal and immunologic responses, and the homeostatic balance between hypertrophy and atrophy or involution. In the human heart apoptosis has been found in the sinus node of patients with the long QT syndrome. It most likely participates in the important postnatal morphogenesis of the sinus node, AV node, and His bundle. Apoptosis may also participate in the genesis and pathophysiology of cardiomyopathy, paroxysmal arrhythmias, or conduction disturbances (some of which may be responsible for sudden death), focal fibromuscular dysplasia of small coronary arteries, hereditary medial degeneration of the tunica media of coronary arteries, and arrhythmogenic right ventricular dysplasia. The possible role apoptosis in numerous other changes in the human heart, among them the pathogenesis of atherosclerosis and mechanisms of aging in the myocardium, merits future investigation.

Congenital disorders of cardiac rhythm and conduction.

Electrical instability of the heart has numerous congenital origins. This review approaches the problems from a morphological standpoint, utilizing selected examples from my own studies of the human cardiac conduction system performed during the last three decades. Subjects discussed include multifocal Purkinje cell tumors, benign congenital polycystic tumors of the AV node, several types of congenital heart block, postnatal morphogenesis of the AV node and His bundle (including considerations of persistent fetal dispersion and crib death), the Wolff-Parkinson-White syndrome, left superior vena cava, focal fibromuscular dysplasia of small coronary arteries, hereditary neuromuscular or musculoskeletal diseases, familial atrial fibrillation, long QT syndrome, and apoptosis of the heart. In many congenital disorders of cardiac electrical activity, both arrhythmias and conduction disturbances may occur. How the abnormal anatomy may relate to cardiac electrical instability is discussed, including certain clinical matters to be considered.

Revascularization in fibromuscular dysplasia of the coronary arteries

vian stenosis, preoperative subclavian arteriography should Fibromuscular dysplasia (FMD) is a nonatherosclerotic, be considered. In addition, subclavian stenosis should be noninflammatory vascular disease. Its etiology is not comcarefully excluded in patients first seen with angina pectopletely understood, and it is generally assumed that the ris after previously successful IMA-coronary bypass surnatural history is relatevely benign. A recent review has gery. suggested that focal FMD of large coronary arteries is ex-

Cardiac abnormalities in the toxic oil syndrome, with comparative observations on the eosinophilia-myalgia syndrome

Early in the course of studies of the Spanish toxic oil syndrome it was recognized that vascular lesions were a major problem, most logically attributable to endothelial damage by the toxic oil. However, most clinical attention has been directed to the pulmonary complications and the evolution into a scleroderma-like illness later. p]In this study of 11 victims of the toxic oil syndrome careful postmortem studies of the coronary arteries and conduction system and neural structures of the heart demonstrated major injury to all those components of the heart. Obliterative fibrosis of the sinus node in four cases resembled findings in fatal scleroderma heart disease, and in eight the cardiac lesions resembled those of lupus erythematosus.The more impressive pathologic features involved the coronary arteries and neural structures, which were abnormal in every heart. The arterial disease included widespread focal fibromuscular dysplasia, but there was also an unusual myointimal proliferative degeneration of both small and large coronary arteries in five patients, four of whom were young women. In two hearts, portions of the inner wall of the sinus node artery had actually detached and embolized downstream. Coronary arteritis was rarely found. Inflammatory and noninflammatory degeneration of cardiac nerves was widespread. Fatty infiltration, fibrosis and degeneration were present in the coronary chemoreceptor.In most respects these cardiac abnormalities resemble those described in the eosinophilia-myalgia syndrome caused by an altered form of l-tryptophan. In both diseases there is good reason to anticipate more clinical cardiac difficulties than have so far been reported, and even more basis for future concern, especially relative to coronary disease and cardiac electrical instability.

Postmortem Studies of the Heart in Three Fatal Cases of the Eosinophilia-Myalgia Syndrome

To examine the hearts of individuals who died from the eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan, with particular attention paid to the coronary arteries, the neural structures, and the conduction system of the heart because of reported terminal disturbances of cardiac rhythm and conduction. Three hearts fixed in neutral formalin and well preserved with all the relevant areas of conduction system intact. Light microscopic examination of subserial sections of the sinus node, atrioventricular node and His bundle, coronary chemoreceptor and regional nerves, ganglia, and small coronary arteries. Routine stains used were Goldner trichrome and Verhoeff-van Gieson. Arterial abnormalities were numerous and primarily of two types: focal fibromuscular dysplasia causing moderate to severe narrowing, as well as endarteritis and panarteritis. Extensive examples of neuritis and ganglionitis were present throughout the heart, including the conduction system, where arterial abnormalities were also abundant. In the coronary chemoreceptor there were both old and new lesions comprising focal inflammation with degeneration as well as older areas of fibrotic destruction. Within the sinus node, areas of dense fibrosis replaced all nodal tissue. These abnormalities were similar in nature and extent in all three hearts. The pathologic lesions present in the coronary arteries, neural structures, and conduction system of the heart in patients who died from the eosinophilia-myalgia syndrome provide a suitable anatomic substrate for substantial cardiac electrical instability, including the occurrence of sudden death. In cases of unexplained cardiac electrical instability or sudden unexpected death an inquiry should be made about previous use of L-tryptophan. In patients with the eosinophilia-myalgia syndrome, the possibility of cardiac electrical instability should be considered as part of long-range clinical management.