Natzi Sakalihasan

Tissue PET) Vascular metabolic imaging and peripheral plasma biomarkers in the evolution of chronic aortic dissections

AIMS Despite adequate medical management, dissection of the descending aorta (type B) may develop complications, including aneurysmal progression and eventually rupture. Partial false lumen thrombosis has been identified as a marker of adverse evolution in chronic dissection. The aim of this study was to test the ability of complementary information, provided by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) and peripheral biomarkers, to add pathophysiological significance and a prognostic value to morphological data. METHODS AND RESULTS We explored serial aortic (18)F-FDG uptake by PET/CT imaging and plasma biomarkers in a series of 23 patients with type B dissection to predict complications from initial data and to investigate potential associations with aneurysmal expansion during follow-up. Complications occurred in 17 patients. Acute initial characteristics associated with complications were male gender (P = 0.021), arterial hypertension (P = 0.040), aortic dissection diameter (P = 0.0086), partial thrombosis of the false channel (P = 0.0046), and enhanced focal (18)F-FDG uptake (P = 0.045). During follow-up (mean 16.7 ± 8.0 months), aneurysmal expansion was associated with false lumen morphology (P< 0.0001), quantitative (18)F-FDG uptake, (P = 0.0029), elevated plasma concentrations of biomarkers of platelets (P-selectin, P = 0.0009) and thrombin activation (TAT complexes, P = 0.0075), and fibrinolysis (PAP complexes, P < 0.0001; D-dimers, P = 0.0006). Plasma markers of coagulation and fibrinolysis were related to false channel morphology, suggesting that thrombus biological dynamics may drive progressive expansion of type B dissections. CONCLUSION Enhanced FDG uptake may be considered as a complementary imaging marker associated with secondary complications in type B dissections. During follow-up, aneurysmal progression is related to PET/CT and biomarkers of thrombus renewal and lysis.

Successful Abdominal Aortic Aneurysm Resection in Long-Term Survivors of Cardiac Transplantation

With the improvement of survival rates following cardiac transplantation, the probability of recipients developing extracardiac disease is increased. Three cases are reported of abdominal aortic aneurysm successfully operated on in cardiac allograft recipients 1 to 4 years after transplantation. Indications for transplantation were valvular, idiopathic and ischaemic cardiomyopathy. Post-transplant hypertension and hyperlipidaemia may have played a role in the rapid growth of the aneurysms. Cardiac function and the incidence of graft atherosclerosis were assessed before surgery by coronary angiography. All three patients were discharged from hospital. Abdominal aortic aneurysm resection may be a safe procedure in cardiac transplant patients. In view of the rapid increase in the size of the aneurysms in transplanted patients, careful screening should be performed during follow-up.

Gene expression study in positron emission tomography-positive abdominal aortic aneurysms identifies CCL18 as a potential biomarker for rupture risk.

Rupture of abdominal aortic aneurysm (AAA) is a cause of significant mortality and morbidity in aging populations. Uptake of 18-fluorodeoxyglucose (FDG) detected by positron emission tomography (PET) is observed in the wall of 12% of AAA (A+), with most of them being symptomatic. We previously showed that the metabolically active areas displayed adventitial inflammation, medial degeneration and molecular alterations prefacing wall rupture. The aim of this study was to identify new factors predictive of rupture. Transcriptomic analyses were performed in the media and adventitia layers from three types of samples: AAA without FDG uptake (A0) and with FDG uptake (A+), both at the positive spot (A+Pos) and at a paired distant negative site (A+Neg) of the same aneurysm. Follow-up studies included reverse-transcriptase-polymerase chain reaction (RT-PCR), immunohistochemical staining and enzyme-linked immunosorbent assay (ELISA). A large number of genes, including matrix metalloproteinases, collagens and cytokines as well as genes involved in osteochondral development, were differentially expressed in the A+Pos compared with A+Neg. Moreover, a series of genes (notably CCL18) was differentially expressed both in the A+Neg and A+Pos compared with the AO. A significant increase of CCL18 was also found at the protein level in the aortic wall and in peripheral blood of A+ patients compared with A0. In conclusion, new factors, including CCL18, involved in the progression of AAA and, potentially, in their rupture were identified by a genome-wide analysis of PET-positive and -negative human aortic tissue samples. Further work is needed to study their role in AAA destabilization and weakening.

On the potential increase of the oxidative stress status in patients with abdominal aortic aneurysm

Abstract Background Abdominal aortic aneurysm (AAA) is a major cause of preventable deaths in older patients. Oxidative stress has been suggested to play a key role in the pathogenesis of AAA. However, only few studies have been conducted to evaluate the blood oxidative stress status of AAA patients. Methods and results Twenty seven AAA patients (mean age of 70 years) divided into two groups according to AAA size (≤50 or >50 mm) were compared with an age-matched group of 18 healthy subjects. Antioxidants (vitamins C and E, β-carotene, glutathione, thiols, and ubiquinone), trace elements (selenium, copper, zinc, and copper/zinc ratio) and markers of oxidative damage to lipids (lipid peroxides, antibodies against oxidized patients, and isoprostanes) were measured in each subject. The comparison of the three groups by ordinal logistic regression showed a significant decrease of the plasma levels of vitamin C (P = 0.011), α-tocopherol (P = 0.016) but not when corrected for cholesterol values, β-carotene (P = 0.0096), ubiquinone (P = 0.014), zinc (P = 0.0035), and of selenium (P = 0.0038), as AAA size increased. By contrast, specific markers of lipid peroxidation such as the Cu/Zn ratio (P = 0.046) and to a lesser extent isoprostanes (P = 0.052) increased. Conclusion The present study emphasizes the potential role of the oxidative stress in AAA disease and suggests that an antioxidant therapy could be of interest to delay AAA progression.

Aneurysm: Epidemiology Aetiology and Pathophysiology

Abdominal aortic aneurysm (AAA) disease is a chronic degenerative disorder and is an important cause of preventable deaths in older patients. Prevalence rates are estimated between 1.3 and 8.9% in men and between 1.0 and 2.2% in women. However, with the aging of the population and the increasing number of smokers, the incidence of the AAA is rising. The prevalence and incidence of thoracic aortic aneurysms (TAA) is more difficult to assess than for the abdominal portion of the aorta due to poorer access to screening. The overall incidence rate of TAAs is estimated at 10.4 per 100,000 person-years. The classical risk factors for atherosclerosis, such as tobacco smoking, male sex, age, hypertension, and hyperlipidemia have all been found to be also risk factors for AAA. The pathophysiology of the aorta above and below the diaphragm has shown significant differences in biomechanical properties, atherosclerotic distribution, proteolytic pattern, and cell signaling pathways that have implications in the development of an aortic aneurysm. During the last decades an overwhelming amount of evidence has been accumulated in support of genetic risk factors contributing to the development, growth and rupture of aneurysms in different segments of the arterial tree. Inflammation and matrix metalloproteinases (MMPs) also play a key role in the pathogenesis of AAA by causing proteolytic degradation of structural proteins. The size of an aneurysm is a universally recognized factor in predicting the probability of rupture; the risk of rupture increases as the diameter of the aneurysm increases. Rupture occasionally occurs in small aneurysms. The risk of rupture and dissection of TAAs also increase with increasing diameter. In addition, not only the size but also the growth rate of the aneurysm has been consistently shown to be critical in predicting rupture.

HLA-DQA is associated with abdominal aortic aneurysms in the Belgian population

Abstract:  Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs using a genetic association study approach with human leukocyte antigen (HLA) polymorphisms (HLA–DQA1, –DQB1, –DRB1 and –DRB3–5 alleles) in 387 AAA cases and 426 controls. We observed an association with the HLA–DQA1 locus among Belgian males, and found a significant difference in the HLA–DQA1*0102 allele frequencies between AAA cases and controls. In conclusion, this study showed potential evidence that the HLA–DQA1 locus harbors a genetic risk factor for AAAs suggesting that autoimmunity plays a role in the pathogenesis of AAAs.

Magnetic Resonance Imaging Findings in a Positron Emission Tomography-Positive Thoracic Aortic Aneurysm

Diffusion-weighted MRI (DW-MRI) and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) findings are described in a patient with a thoracic aortic aneurysm. Both examinations have the ability to noninvasively assess biological processes associated with aneurysm instability and therefore to potentially impact clinical decision-making regardless of the vessel size. Despite similarities between images on both techniques, FDG-PET evaluates glycolysis, while DW-MRI evaluates cell density, edema, and perfusion. Longitudinal studies including larger patient numbers are needed to investigate the temporal continuum and clinical significance of these findings.

A novel SMAD3 mutation caused multiple aneurysms in a patient without osteoarthritis symptoms

Heterozygous mutations in the SMAD3 gene were recently described as the cause of a form of non-syndromic familial aortic thoracic aneurysm and dissection (FTAAD) transmitted as an autosomal dominant disorder and often associated with early-onset osteoarthritis. This new clinical entity, called aneurysms-osteoarthritis syndrome (AOS) or Loeys-Dietz syndrome 3 (LDS3), is characterized by aggressive arterial damages such as aneurysms, dissections and tortuosity throughout the arterial tree. We report, here, the case of a 45 year-old man presenting multiple visceral arteries and abdominal aortic aneurysms but without dissection of the thoracic aorta and without any sign of osteoarthritis. Exome-sequencing revealed a new frameshift heterozygous c.455delC (p.Pro152Hisfs*34) mutation in the SMAD3 gene. This deletion is located in the exon 3 coding for the linker region of the protein and causes a premature stop codon at positions 556-558 in the exon 4. The same mutation was found in the probands mother and sister who had open surgery for abdominal aortic aneurysm and in one of his children who was 5 year-old and did not present aneurysm yet.

Increased Metabolic Activity Highlighted by Positron Emission Tomography/Computed Tomography in the Wall of the Dissected Ascending Aorta in a Patient With Horton Disease

Horton disease or giant-cell arteritis (GCA) is a chronic systemic vasculitis involving typically medium and large arteries. Giant-cell arteritis is a panarteritis characterized by a granulomatous inflammation, with lymphocytes, macrophages, and multinucleated giant cells related to autoimmune T-cell reactivity.1 Compared with conventional imaging tools (ultrasound, computed tomography (CT), MRI, and contrast angiography) that provide anatomic and morphological information, recent available imaging techniques such as positron emission tomography (PET)/CT provide metabolic assessment of the arterial wall. During the early 2000s, Sakalihasan et al2 observed a close correlation between clinically unstable abdominal aortic aneurysms and increased uptake of 18F-fluoro-2-deoxy-d-glucose (FDG) in the aneurysmal wall. A few years later, Hautzel et al3 studied the assessment of giant-cell arteritis with PET/CT. We describe a case of Horton disease involving the thoracic aorta and complicated with acute aortic dissection in a woman with a previous diagnosis of thoracic aortic aneurysm. In July 2011, a 66-year-old woman was referred to a cardiology center for evaluation of a recent mild hypertension related to use of high doses of corticosteroids. In December 2010, she had developed severe headache, rapid loss of weight, and elevation of sedimentation rate as high as 120 mm. Horton disease was diagnosed in April 2011 on temporal artery biopsy. During the first cardiologic examination, …

Urgent Carotid Endarterectomy in Patients with Acute Neurological Symptoms: The Results of a Single Center Prospective Nonrandomized Study.

BACKGROUND To evaluate the feasibility and the safety of performing urgent (within 24 hours) carotid endarterectomy in patients with carotid stenosis presenting with repetitive transient ischemic attacks or progressing stroke. METHODS Thirty consecutive patients underwent urgent carotid endarterectomy for repetitive transient ischemic attacks (N = 12) or progressing stroke (N = 18) according to the following criteria: two or more transient ischemic attacks or a fluctuating neurological deficit over a period of less than 24 hours (progressing stroke), no impairment of consciousness, no cerebral infarct larger than 1.5 cm in diameter on computed tomography and a carotid artery stenosis of 70% or more on the appropriate side, diagnosed by echodoppler ultrasonography and/or arteriography. Patients with cerebral hemorrhage were excluded. All patients were examined pre- and postoperatively by the same neurologist and surgery was performed by the same vascular surgeon. All the patients underwent a cerebral CT scan within 5 days after surgery. RESULTS There were 19 men and 11 women. The mean age was 71 ± 7.6 years. The time delay of surgery after the onset of transient ischemic attacks or progressing stroke averaged 19.4 ± 11.5 hours. For patients suffering progressive stroke, one developed a fatal ischemic stroke 24 hours after surgery, five showed no improvement of their neurological status after surgery, but none worsened. Twelve patients experienced significant improvement of their neurological status with an European Stroke Scale of 77.9 ± 25.2 at admission and 95.8 ± 4.6 at discharge, and all but one of those patients had a Barthels index value over 85/100 at discharge. The 12 patients with repetitive transient ischemic attacks had an uneventful postoperative outcome. The mean duration of follow-up was 3.4 ± 1.2 years. No patient developed another transient ischemic attack or ischemic stroke during the follow-up period. CONCLUSIONS The results of our series documented the feasibility and the safety of performing urgent (within 24 hours) carotid endarterectomy in patients presenting with repetitive transient ischemic attacks or progressing stroke. This procedure seems to us to be justified by the fact that waiting for surgery may lead to the development of a more profound deficit or another stroke in these neurologically unstable patients whose only chance for neurological recovery is in the early phase.