Spontaneous visceral artery dissections in otherwise normal arteries: Clinical features, management, and outcomes compared with fibromuscular dysplasia.

OBJECTIVE: Visceral artery dissection with otherwise normal-appearing arteries (VADNA), diagnosed on imaging and suggestive of segmental arterial mediolysis, is a poorly understood disease entity. Study objectives were to define the clinical features, management, and outcomes of patients with VADNA compared with patients with fibromuscular dysplasia (FMD). METHODS: In this single-center retrospective cohort study, consecutive patients with a diagnosis of VADNA or FMD evaluated in the Mayo Clinic Gonda Vascular Center (January 1, 2000-April 1, 2017) were identified. Patient demographics, symptom presentation, management, composite adverse arterial events (recurrent arterial dissection, stroke or transient ischemic attack, myocardial infarction, mesenteric or renal infarction, or need for revascularization), and overall survival were compared between VADNA and FMD patients. RESULTS: There were 103 VADNA patients (age [mean ± standard deviation], 51.7 ± 11.0 years; 27.9% female) and 248 FMD controls (49.8 ± 8.9 years; 81.8% female) identified. The most common symptom for VADNA patients was abdominal or flank pain (80.6%). For FMD, chest pain, headache, and dizziness were more frequent presenting complaints. The median follow-up was longer for VADNA patients (42 months; interquartile range, 9-76 months) compared with FMD patients (19 months; interquartile range, 0.6-52 months; P < .001). During this time interval, there were twofold more composite arterial events in the VADNA group compared with the FMD group (17% vs 8.1%; P = .01). This difference was primarily driven by recurrent dissections. All-cause mortality was low and similar for both groups (3.8% vs 0.4%; P = .10). CONCLUSIONS: VADNA patients carry a higher risk of recurrent arterial events compared with those with FMD. This difference was primarily driven by recurrent dissections.

Incidence and Etiology of Sudden Cardiac Arrest and Death in High School Athletes in the United States.

OBJECTIVE: To determine the incidence and etiology of sudden cardiac arrest and death (SCA/D) in US high school athletes. PATIENTS AND METHODS: A prospective media database of SCA/D was queried for cases aged 14 to 18 years from 7 states over 6 school years (September 1, 2007, to August 30, 2013). Event details were investigated to determine participation on a high school athletic team, sex, sport, and occurrence during school-sponsored activity or exertion. National sports participation numbers were used and a conversion factor was applied to account for multisport athletes. Autopsy reports were reviewed and cause of death was adjudicated by an expert panel. RESULTS: A total of 16,390,409 million athlete-seasons representing 6,974,640 athlete-years (AY) were examined, encompassing 36% of the total US high school athlete population. A total of 104 cases of SCA/D were identified (35 SCA with survival and 69 sudden cardiac deaths [SCDs]). The rate of SCD was 1:101,082 AY and of SCA/D 1:67,064 AY. Eighty-eight percent (92) of events occurred in male athletes. The rate of SCA/D in male athletes was 1:44,832 AY and in female athletes 1:237,510 AY (incidence rate ratio, 5.3; 95% CI, 2.9-10.6; P<.001). Men's basketball was the highest risk sport with an SCA/D incidence of 1:37,087 AY followed by men's football at 1:86,494 AY. Men's basketball and football athletes accounted for 57% (39) of deaths. Eighty percent of SCDs (55 of 69) were exertional and 55% (38 of 69) occurred while playing for a school-sponsored team. Autopsy reports were obtained in 73% (50) of cases. The most common findings of autopsy were idiopathic left ventricular hypertrophy or possible cardiomyopathy (13 of 50 [26%]), autopsy-negative sudden unexplained death (9 of 50 [18%]), hypertrophic cardiomyopathy (7 of 50 [14%]), and myocarditis (7 of 50 [14%]). CONCLUSION: The rate of SCA/D in male high school athletes was 1:44,832 AY, with almost half due to possible or confirmed cardiomyopathy disease. It is likely that many cases were not identified because of reliance on media reports, and these numbers represent a minimum estimate.

Clinical characteristics and treatment of renal artery fibromuscular dysplasia with percutaneous transluminal angioplasty: a long-term follow-up study.

BACKGROUND: Renal artery fibromuscular dysplasia (RAFMD) is a non-atherosclerotic cause of renal artery stenosis often affecting the young. Percutaneous transluminal renal angioplasty (PTRA) is the treatment of choice but there are few studies of the outcome of the procedure. METHODS: This retrospective analysis included 64 patients (56.2 % female; mean age at diagnosis, 28.0 years) with RAFMD who underwent PTRA between November 2003 and August 2015. Technical and clinical success rates and restenosis rates were evaluated. RESULTS: Seventy-six procedures were performed on 64 RAFMD patients. Technical success was 96.9 %, as defined by <30 % residual stenosis, with stent placement required in 11 patients (17.2 %). In the short term (1 month), the majority (79.7 %) had an immediate clinical benefit, with cure of hypertension in 35.9 %, and improvement in hypertension and a lower requirement for antihypertensive medications in 43.8 %. In the long term (mean, 47.5 months; range, 5-141 months), the survival rate was 96.9 %, freedom from restenosis was 84.4 %, and 76.6 % of patients showed a sustained clinical benefit (cure rate 40.6 %, improvement rate 35.9 %). Eight patients were treated with a second procedure and two had a third procedure, with half of these patients showing an improvement in hypertension. CONCLUSION: PTRA for symptomatic RAFMD is safe and clinically successful. More than half of patients experience an immediate clinical benefit with sustained long-term effects. For patients with restenosis, there was a good response to a second PTRA.

Coronary artery manifestations of fibromuscular dysplasia.

Fibromuscular dysplasia (FMD) involving the coronary arteries is an uncommon but important condition that can present as acute coronary syndrome, left ventricular dysfunction, or potentially sudden cardiac death. Although the classic angiographic "string of beads" that may be observed in renal artery FMD does not occur in coronary arteries, potential manifestations include spontaneous coronary artery dissection, distal tapering or long, smooth narrowing that may represent dissection, intramural hematoma, spasm, or tortuosity. Importantly, FMD must be identified in at least one other noncoronary arterial territory to attribute any coronary findings to FMD. Although there is limited evidence to guide treatment, many lesions heal spontaneously; thus, a conservative approach is generally preferred. The etiology is poorly understood, but there are ongoing efforts to better characterize FMD and define its genetic and molecular basis. This report reviews the clinical course of FMD involving the coronary arteries and provides guidance for diagnosis and treatment strategies.

Small bowel adenocarcinomas complicating Crohn's disease are associated with dysplasia: a pathological and molecular study.

BACKGROUND: Crohn's disease (CD) is associated with an increased risk of small bowel adenocarcinoma (SBA). However, there are no guidelines for the screening and early diagnosis of SBA. Colorectal cancer associated with chronic colitis arises from dysplasia. High-risk patients benefit from surveillance colonoscopies aimed to detect dysplasia. The dysplasia-carcinoma sequence remains poorly documented in CD-associated SBA. Moreover, molecular data about SBA complicating CD and associated dysplasia are very limited. We therefore assessed dysplasia and several key molecular markers of carcinogenesis in SBA and dysplasia developed in patients with CD. METHODS: Forty-five SBA complicating CD and 4 specimens with dysplasia without SBA were screened. In SBA, we looked for dysplasia and determined their pathological characteristics (type, grade, distribution). We also stained for mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), p53, ß-catenin, and p16 and looked for KRAS, BRAF and PIK3CA mutations. RESULTS: All neoplastic lesions, except 1 lesion, were found in inflamed mucosal areas. Dysplasia was found in 20 of 41 patients with SBA (49%). Dysplasia was flat or raised, low grade or high grade, and adjacent or distant to concomitant SBA. Molecular markers of SBA carcinogenesis complicating CD were similar to those observed in chronic colitis-related colorectal cancer (KRAS, BRAF, p53, MSI), although differences were observed for ß-catenin and p16. No PIK3CA mutations were observed. CONCLUSIONS: These results suggest that there is an inflammation-dysplasia-adenocarcinoma sequence in at least half of CD-related SBA, similar to what is observed in chronic colitis-related colorectal cancer and may have implications for the prevention and treatment of this cancer.

Fibromuscular dysplasia of cardiac conduction system arteries in traumatic and nonnatural sudden death victims aged 0 to 40 years: a histological analysis of 100 cases.

BACKGROUND: Since 1967, numerous case reports have described fibromuscular alterations of the sinus node artery and/or the atrioventricular node artery as a potential cause of death. However, the prevalence of these changes in a healthy population has only rarely been investigated systematically. METHODS: The arteries of the cardiac conduction system were studied systematically, by means of routine histology, in 100 cases of victims aged 0 to 40 years with a nonnatural cause of death. RESULTS: Microscopic alterations were seen in the walls of sinus node arteries in 52 out of 100 cases, in the walls of atrioventricular node arteries in 63/100 cases, and in the walls of small vessels in 60/100 cases. CONCLUSIONS: The results demonstrate that microscopically detectable findings of the cardiac conduction system arteries similar to fibromuscular dysplasia do not indicate a defined disease and should not be considered as a cause of death when there are no macroscopic findings in the coronary arteries.

Short- and long-term outcomes of percutaneous transluminal angioplasty/stenting of renal fibromuscular dysplasia over a ten-year period.

OBJECTIVES: The purpose of this study was to evaluate short and long-term outcomes of percutaneous transluminal intervention in patients with symptomatic renal artery stenosis due to fibromuscular dysplasia (RAFMD) and/or the combination of RAFMD with aorto-ostial atherosclerotic disease. METHODS: A retrospective analysis of all patients with renal artery RAFMD who underwent transcatheter therapy between January 1999 and December 2009 was performed. Blood pressure (BP) measurement, number of BP medications, and hypertension defined by a systolic BP >140 ± diastolic BP >90 were recorded. Renal function was defined by estimated glomerular filtration rate (eGFR). Restenosis was defined by stenosis >60% and was determined by renal artery duplex and/or angiography. Freedom from event (restenosis, renal failure, or recurrent hypertension) was performed using life table analysis. RESULTS: Forty-three procedures were performed on 35 patients with RAFMD. Thirty-two patients (91%) were women, with mean age of 61.9 years old. Technical success was 100% with adjunctive stent placement required in the FMD segment for dissection in 1 patient (2.3%) and in the non-FMD aorto-ostial atherosclerotic lesion in 4 patients (9.3%). Short-term outcomes: the majority (69%) had an immediate clinical benefit for hypertension, 6% were cured without BP medications, and 63% improved with less than or equal to preoperative BP medications. Postintervention, 17% remained at moderately reduced renal function (<60), whereas the percent above >60 mL/minute eGFR increased significantly (from 51% to 69%; P = .002). For the entire cohort, renal function (mean eGFR) significantly increased from 71.9 mL/minute + 5.8 to 80.8 mL/minute + 5.2 (P = .007). Long-term outcomes: freedom from recurrent or worsening hypertension (>140 systolic blood pressure [SBP] and >90 diastolic blood pressure [DBP]) was (93%, 75%, and 41%) and freedom from reduced renal function (eGFR <30 mL/minute) was (100%, 95%, and 64%) at 1, 5, and 8 years, respectively. Patients with reduced baseline renal function (<60 mL/minute) and combined atherosclerotic disease were more likely to experience long-term reduced renal function (eGFR <30 mL/minute; P = .003). Primary and assisted primary patency was (95%, 71%, and 50%) and (100%, 100%, and 100%) at 1, 5, and 9 years, respectively. CONCLUSION: Renal angioplasty is a safe and durable modality for treating RAFMD with favorable short and long-term clinical outcomes. Patients with combined atherosclerotic disease and FMD were older and were more likely to have declining renal function over time. Early intervention may be imperative to achieve possible cure of hypertension.

Lipoprotein(a) predicts progression of carotid artery intima-media thickening in patients with type 2 diabetes: A four-year follow-up.

BACKGROUND: The aim of the study was to establish whether increased levels of serum lipoprotein(a) significantly contribute to an increase in intima-media thickness and the number of carotid artery plaques, and consequently to cardiovascular risk in patients with type 2 diabetes mellitus. METHODS: Lipoprotein(a) levels, intima-media thickness and the number of carotid artery plaques were determined at the beginning of the study in 146 patients with type 2 diabetes. Patients were divided into two groups according to serum lipoprotein(a) levels (> or 30 mg/dl had more cardiovascular events, the difference was not statistically significant. CONCLUSIONS: These results indicate that lipoprotein(a) is an independent, genetically determined risk factor closely associated with progression of intima-media thickness in type 2 diabetes.

Cardiac allograft vasculopathy: pathology, prevention and treatment.

PURPOSE OF REVIEW: Cardiac transplantation is a recognized therapy for end-stage heart failure. Graft coronary artery disease is a chief determinant of long-term survival following cardiac transplantation. There are multiple purported etiologies for graft coronary artery disease including both immunologic and nonimmunologic factors. Immunologic factors include human leukocyte antigen mismatching, cytokine production, and activation of the cellular immune system. Nonimmunologic factors include diabetes, hypertension, hyperlipidemia, and cytomegalovirus infection, just to name a few. There are also donor and recipient factors including age, prior coronary artery disease in the donor heart, and mode of donor brain death. RECENT FINDINGS: The diagnosis of graft coronary artery disease is especially difficult, partially due to the de-innervated allograft, as well as to its inherent predilection to affect the medium-sized and smaller arteries in a concentric and diffuse nature. Conventional angiography can overlook this condition because of the lack of eccentric plaques in larger epicardial arteries. Intravascular ultrasonography, by contrast, is more sensitive in detecting graft coronary artery disease but is unable to visualize the entire arterial system. Treatment is challenging and often unrewarding, leading to re-transplantation. Prevention is therefore ideal and involves protection against endothelial injury before and during transplantation as well as after transplantation, with decreased ischemic time, aggressive attention to early rejection, risk factor modification, and close follow-up. SUMMARY: This review will look at the pathophysiology of graft coronary artery disease, current diagnostic and therapeutic choices, as well as existing and future directions.

Excessive carotid in-stent neointimal formation predicts late cardiovascular events.

PURPOSE: To examine if excessive in-stent neointimal formation causing a subcritical stenosis may indicate enhanced vascular reactivity in response to injury, thus predicting late cardiovascular events. METHODS: One hundred consecutive patients (64 men; median age 71 years) with high-grade internal carotid artery stenoses (68 asymptomatic, 32 symptomatic) underwent carotid artery stenting (CAS). High-sensitivity C-reactive protein (hs-CRP) was measured before CAS. Patients were monitored with duplex ultrasound for excessive in-stent neointimal formation (flow-compromising lumen diameter reduction >/=50%), critical restenosis (>/=70%), or the occurrence of late major adverse cardiovascular events (MACE) defined as myocardial infarction (MI), stroke, and death occurring later than 30 days poststenting. RESULTS: Over a median 23-month follow-up, excessive neointimal formation was observed in 14 (14%) patients, restenosis in 2 (2%), and 30 late MACE in 25 [25%: 4 MIs, 2 ipsilateral strokes (in the patients with restenosis), 8 contralateral strokes, and 16 cardiovascular deaths]. Cumulative MACE-free survival rates at 6, 12, and 24 months were 92%, 84%, and 77%, respectively. Baseline hs-CRP levels were associated both with neointimal hyperplasia (p=0.024) and MACE (p=0.021). Patients with excessive neointimal formation exhibited a significantly increased adjusted risk for MACE (hazard ratio 3.56, p=0.010). CONCLUSIONS: Excessive in-stent neointimal formation after CAS indicates an increased risk for late MACE, potentially reflecting a state of exaggerated vascular reactivity in response to injury. Inflammation, which is associated both with neointimal hyperplasia and MACE, seems a common characteristic of different vascular pathologies.

Long-term results after surgical reconstruction for renal artery fibromuscular dysplasia.

OBJECTIVES: To study the initial and long-term results of surgery for renal artery fibromuscular dysplasia (RFMD). PATIENTS AND METHODS: All patients undergoing renal artery reconstruction (RAR) performed for RFMD between January 1980 and December 1997, were studied. The preprocedural and postprocedural clinical records of 101 patients (80 women, 21 men; mean age at surgery 43 years) were retrospectively reviewed. All surviving patients were invited for clinical reexamination and colour-coded duplex-ultrasound of the renal arteries (RA). RESULTS: Initial technical success was achieved in 83 of 93 patients (89%), in whom postoperative angiography (90) or renal scintigraphy (three) were performed for assessment of RAR. Early occlusion (four) or stenosis (one) demanded reoperation in five patients (5%). The 30-day mortality and morbidity were 2% and 12% for the entire group. Primary patency rate was 74% at 5 years. Fifteen patients had to be reoperated for restenosis after a mean time of 33 months, resulting in a secondary patency rate of 85% after 5 years. In 61 patients with patent RAR at the time of re-examination, arterial hypertension was cured only in 22 (36%) and improvement in 19 (31%). CONCLUSION: Vascular surgery for RFMD yields good long-term results as to kidney perfusion and function. Surveillance of RAR-patency by means of ultrasound examination is mandatory in case of recurrence of arterial hypertension or deterioration. Rates of cure of hypertension are disappointing.

Intramural coronary artery dysplasia of the ventricular septum and sudden death.

We report four cases of sudden unexpected death in three males and one female aged 12 to 31 years. Death occurred during exercise in three of four cases, and there was no history of sudden death or previous cardiac history in any patient. At autopsy, there was marked intramural coronary artery dysplasia of the ventricular septum, accompanied in three of the four cases by myocardial fibrosis. The arterial dysplasia was characterized by severe medial thickening with smooth muscle cell disorganization and marked luminal narrowing. There was no evidence of myofiber disarray or asymmetric septal hypertrophy to suggest hypertrophic cardiomyopathy. Other than an ostium secundum type atrial septal defect in one case, there were no associated cardiac or extracardiac lesions found at complete autopsy of these individuals. We conclude that small vessel disease of intramural coronary arteries of the ventricular septum may be an isolated finding leading to sudden cardiac death in young adults.

Occlusive fibromuscular disease of arteries supplying the brain: results of surgical treatment.

Occlusive fibromuscular disease (FMD) of arteries supplying the brain is a documented cause of neurologic complications. From September 1976 to December 1994, 70 patients underwent surgery for occlusive FMD involving arteries supplying the brain. Isolated dysplastic aneurysms and coilings or kinkings were not included in this series. Twenty-two patients had experienced previous nonlethal ischemic stroke, 25 patients had experienced transient ischemic attacks, and 32 patients had vertebrobasilar insufficiency with or without associated carotid symptoms. Lesions involved one (n = 36) or two (n = 29) internal carotid arteries, and one (n = 18) or two (n = 14) vertebral arteries. Twenty-seven patients had simultaneous involvement of both carotid and vertebral arteries. Ten patients had FMD at another site, four had intracranial aneurysm, and four had an aberrant right subclavian artery. Seventy-seven carotid procedures including 67 graduated intraluminal dilatations were performed and 18 vertebral arteries were revascularized. One patient (1.4%) died postoperatively from hemorrhagic stroke and two patients (2.8%) presented nonlethal stroke. Sixty-two patients were followed postoperatively from 2 to 184 months (mean 86.2 +/- 54.4). Actuarial survival rates at 5 and 10 years were 96.4 +/- 5.0% and 82.1 +/- 14.9%, respectively. Actuarial primary patency rate at 5 and 10 years was 94.3 +/- 5.5%. Actuarial probability of stroke-free survival rates at 5 and 10 years were 94.2 +/- 5.6% and 88.6% +/- 10.3%, respectively. We conclude that improvement of symptoms, prevention of stroke, and stable long-term results justify surgical treatment in symptomatic patients with FMD of arteries supplying the brain.

Natural history of renal artery stenosis.

The natural history of various types of renal artery stenosis is reviewed. Atherosclerotic renal artery stenosis is obviously a progressive disease, with a relatively high incidence of occlusions, particularly when the stenosis is narrow. Much less is known about other types of renal artery stenosis. Medial fibroplasia is obviously a disease which progresses during fertile life, but the course is rather unpredictable. Very little is known about the developmental types of renal artery stenosis.

Long-term prognosis of surgical treatment of renovascular hypertension.

During the period 1974-1986, 71 patients were operated on for renovascular hypertension. Forty-eight patients had atherosclerotic disease and 23 patients had fibromuscular dysplasia. There was no operative mortality. Fourteen patients died during the follow-up, 12 of them from cardiovascular causes. The 57 surviving patients were reexamined with a mean follow-up of 7 years. The relative cumulative 5- and 10-year survival rates in all patients were 79% and 55%, respectively. At follow-up, seven (19%) of the atherosclerotic patients were classified as cured, 22 (59%) as improved and eight (22%) as failures. In the patients with fibromuscular dysplasia, 12 (60%) were normotensive without medication, and six (30%) were improved. The relative 5-year survival rates in these aetiological groups were 73% and 90%, respectively. Only complete cure of hypertension by surgery predicted a good outcome, whereas very similar survival curves were found in the improved and failed groups. This could be due to a higher incidence of target organ changes before surgery in the latter groups. A positive blood pressure response to long-term converting-enzyme inhibition correlated well with the response to surgery. Renal venous renin studies correctly predicted long-term outcome of surgery in 78% of the patients studied, but require careful preparation of the patients and interpretation of results.