Multidisciplinary aortopathy clinics: A systematic scoping review of the literature and evaluation of patient experiences from a newly started clinic in Norway.

BACKGROUND: International guidelines recommend hereditary thoracic aortic diseases (HTADs) to be managed in multidisciplinary aorta clinics. AIM: To study HTAD patient's experiences with a aortopathy clinic in Norway and to review the literature on aortopathy clinics. METHODS: (a) A systematic scoping review of research on multidisciplinary clinics for HTADs. (b) A cross-sectional postal questionnaire study to investigate patient experiences with the health-services. Fifty consecutive patients from the aortopathy clinic and 50 controls in usual care were invited to participate. RESULTS: The review identified eight publications on aortopathy clinics. Although the papers were not judged for quality, these showed promising results from such clinics in terms of diagnostics and increased adherence to guideline-directed therapy. The survey constituted thirty-seven (74%) patients and 22 (44%) controls who responded to postal questionnaires. Both groups reported delays in diagnostics and follow-up appointments prior to the start of the clinic. Patients indicated high satisfaction with the aortopathy clinic, whereas controls reported poor coordination of medical follow-up. Individuals in both groups struggled with disease self-management. CONCLUSION: Norwegian patient experiences found the aortopathy clinic beneficial. According to studies included in the review, disease management in aortopathy clinics may improve patient satisfaction, diagnostics and follow-up. Effect studies may further document the benefits of clinic organization, treatment, cost-efficiency and patient experiences.

Marfan syndrome: Evolving organ manifestations-A 10-year follow-up study.

The age-dependent penetrance of organ manifestations in Marfan syndrome (MFS) is not known. The aims of this follow-up study were to explore how clinical features change over a 10-year period in the same Norwegian MFS cohort. In 2003-2004, we investigated 105 adults for all manifestations in the 1996 Ghent nosology. Ten years later, we performed follow-up investigations of the survivors (n = 48) who consented. Forty-six fulfilled the revised Ghent criteria. Median age: females 51 years, range 32-80 years; males 45 years, range 30-67 years. New aortic root dilatation was detected in patients up to 70 years. Ascending aortic pathology was diagnosed in 93 versus 72% at baseline. Sixty-five percent had undergone aortic surgery compared to 39% at baseline. Pulmonary trunk mean diameter had increased significantly compared to baseline. From inclusion to follow-up, two patients (three eyes) developed ectopia lentis, four developed dural ectasia, four developed scoliosis, three developed incisional or recurrent herniae, and 14 developed hindfoot deformity. No changes were found regarding protrusio acetabuli, spontaneous pneumothorax, or striae atrophicae. The study confirms that knowledge of incidence and progression of organ manifestations throughout life is important for diagnosis, treatment, and follow-up of patients with verified or suspected MFS.

Semiautomated Magnetic Resonance Imaging Assessment of Carotid Plaque Lipid Content.

BACKGROUND: The composition of a carotid plaque is important for plaque vulnerability and stroke risk. The main aim of this study was to assess the potential of semiautomated segmentation of carotid plaque magnetic resonance imaging (MRI) in the assessment of the size of the lipid-rich necrotic core (LRNC). METHODS: Thirty-four consecutive patients with carotid stenosis of 70% or higher, who were scheduled for carotid endarterectomy, underwent a clinical neurological examination, Color duplex ultrasound, 3-T MRI with an 8-channel carotid coil, and blood tests. All examinations were performed less than 24 hours prior to surgery and plaques were assessed histologically immediately following endarterectomy. Plaques were defined as symptomatic when associated with ipsilateral cerebral ischemic symptoms within 30 days prior to inclusion. The level of agreement between the size of the LRNC and calcification on MRI to the histological estimation of the same tissue components, plaque echolucency on ultrasound, and symptoms was assessed. RESULTS: The size of the LRNC on MRI was significantly correlated to the percentage amount of lipid per plaque on histological assessment (P = .010, r = .5), and to echogenicity on ultrasound with echolucent plaques having larger LRNC than echogenic plaques (P = .001, r = -.7). CONCLUSIONS: In this study, we found that semiautomated MRI assessments of the percentage LRNC in carotid plaques were significantly correlated to the percentage LRNC per plaque on histological assessment, and to echogenicity on ultrasound with echolucent plaques having larger LRNC than echogenic plaques.

Interleukin 23 levels are increased in carotid atherosclerosis: possible role for the interleukin 23/interleukin 17 axis.

BACKGROUND AND PURPOSE: Interleukin (IL)-23 is a cytokine in the IL-12 family, mainly produced by antigen-presenting cells with a central role in inflammation. We hypothesize that IL-23 is also important in atherogenesis and investigate this in a population with carotid atherosclerosis. METHODS: Plasma levels of IL-23 were measured in patients with carotid artery stenosis and in healthy controls. The mRNA levels of IL-23 and its receptor, IL-23R, were measured in atherosclerotic plaques, nonatherosclerotic vessels, peripheral blood mononuclear cells, and plasmacytoid dendritic cells. RESULTS: Our findings were as follows: (1) patients with carotid atherosclerosis (n=177) had significantly raised plasma levels of IL-23 when compared with healthy controls (n=24) with particularly high levels in those with the most recent symptoms. (2) mRNA levels of IL-23 and IL-23R were markedly increased in carotid plaques (n=68) when compared with nonatherosclerotic vessels (n=8-10). Immunostaining showed colocalization to plaque macrophages. (3) Patients with carotid atherosclerosis had increased mRNA levels of both IL-23 and IL-23R in plasmacytoid dendritic cells, but not in peripheral blood mononuclear cells. (4) IL-23 increased IL-17 release in monocytes and particularly in peripheral blood mononuclear cells from patients with carotid atherosclerosis, but not in cells from healthy controls. (5) IL-23 gave a prominent tumor necrosis factor release in monocytes from patients with carotid atherosclerosis but not in cells from healthy controls. (6) High plasma levels of IL-23 were associated with increased mortality during follow-up. CONCLUSIONS: We have shown an association between IL-23 and disease progression in patients with carotid atherosclerosis, potentially involving IL-17-related mechanisms.

The use of segregation analysis in interpretation of sequence variants in SMAD3: A case report.

BACKGROUND: While representing a significant improvement, the introduction of next-generation sequencing in genetic diagnosis also prompted new challenges. Despite widely recognized consensus guidelines for the interpretation of sequence variants, many variants remain unclassified or are discordantly interpreted. In heritable thoracic aortic aneurysms with dissection (HTAAD), most cases are caused by a heterozygous, private missense mutation, possibly contributing to the relatively common reports of variants with uncertain significance in this group. Segregation analysis necessitates advanced likelihood-based methods typically inaccessible to non-experts and is hampered by reduced penetrance, possible phenocopies, and non-availability of DNA from deceased relatives. METHODS: In this report, challenges in variant interpretation and the use of segregation analyses were illustrated in two families with a suspected HTAAD disorder. The R package segregatr, a novel implementation of full-likelihood Bayes factor (FLB), was performed to explore the cosegregation of the variants in these families. CONCLUSION: Using the R package segregatr, cosegregation in the reported families concluded with strong and supporting evidence for pathogenicity. Surveillance of families in a multidisciplinary team enabling systematic phenotype description for standardized segregation analysis with a robust calculation method may be imperative for reliable variant interpretation in HTAAD.

High levels of S100A12 are associated with recent plaque symptomatology in patients with carotid atherosclerosis.

BACKGROUND AND PURPOSE: Atherosclerosis is a progressive chronic disease, in which inflammation plays a key role. The calcium-binding proteins calgranulins including S100A8, S100A9, and S100A12 are involved in many cellular activities and pathological processes including inflammation. We therefore hypothesized that calgranulins may be markers of plaque instability in patients with carotid atherosclerosis. METHODS: Plasma levels of S100A8/A9 and S100A10 were measured in 159 consecutive patients with high-grade carotid stenosis and in 22 healthy control subjects. The mRNA levels of calgranulins were also measured within the atherosclerotic carotid plaques, and their regulation was analyzed in vitro in monocytes. RESULTS: Our main findings were: (1) plasma levels of S100A12 were significantly higher in patients with carotid atherosclerosis compared with healthy control subjects with the highest levels in patients with the most recent symptoms (ie, within 2 months); (2) plasma levels of S100A8/S100A9 showed a modest increase in patients with symptoms in the previous 2 to 6 months but not in the other patients; (3) mRNA levels of S100A8, S100A9, and S100A12 showed increased expression in atherosclerotic carotid plaques from patients with the most recent symptoms compared with the remaining patients; (4) in THP-1 monocytes, activation of Toll-like receptors 2 and 4 increased mRNA levels of S100A8, S100A9, and S10012 and interleukin-1ß, interferon γ, and releasate from thrombin-activated platelets significantly enhanced the expression of S100A12. CONCLUSIONS: Our findings support a link between calgranulins and atherogenesis and suggest that these mediators, and in particular S100A12, may be related to plaque instability.

Markers of extracellular matrix remodeling and systemic inflammation in patients with heritable thoracic aortic diseases.

Background: In approximately 20% of patients with thoracic aortic aneurysms or dissections a heritable thoracic aortic disease (HTAD) is suspected. Several monogenic connective tissue diseases imply high risk of aortic disease, including both non-syndromic and syndromic forms. There are some studies assessing inflammation and extracellular matrix remodeling in patients with non-hereditary aortic disease, but such studies in patients with hereditary diseases are scarce. Aims: To quantify markers of extracellular matrix (ECM) and inflammation in patients with vascular connective tissue diseases versus healthy controls. Methods: Patients with Loeys-Dietz syndrome (LDS, n = 12), Marfan syndrome (MFS, n = 11), and familial thoracic aortic aneurysm 6 (FTAA6, n = 9), i.e., actin alpha 2 (ACTA2) pathogenic variants, were recruited. Exome or genome sequencing was performed for genetic diagnosis. Several markers of inflammation and ECM remodeling were measured in plasma by enzyme immunoassays. Flow cytometry of T-cell subpopulations was performed on a subgroup of patients. For comparison, blood samples were drawn from 14 healthy controls. Results: (i) All groups of HTAD patients had increased levels matrix metalloproteinase-9 (MMP-9) as compared with healthy controls, also in adjusted analyses, reflecting altered ECM remodeling. (ii) LDS patients had increased levels of pentraxin 3 (PTX3), reflecting systemic inflammation. (iii) LDS patients have increased levels of soluble CD25, a marker of T-cell activation. Conclusion: Our data suggest that upregulated MMP-9, a matrix degrading enzyme, is a common feature of several subgroups of HTAD. In addition, LDS patients have increased levels of PTX3 reflecting systemic and in particular vascular inflammation.

Mitral annulus disjunction is associated with adverse outcome in Marfan and Loeys-Dietz syndromes.

AIMS: We aimed to assess the prevalence of mitral annulus disjunction (MAD) and to explore the association with aortic disease and mitral valve surgery in patients with Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). METHODS AND RESULTS: We included consecutive MFS patients fulfilling Revised Ghent Criteria and LDS patients fulfilling Loeys-Dietz Revised Nosology. MAD was identified by echocardiography and was quantified as the longitudinal distance from the ventricular myocardium to the hinge point of the posterior mitral leaflet. Aortic events were defined as aortic dissection or prophylactic aortic surgery. We recorded the need of mitral valve surgery including mitral valve repair or replacement. We included 168 patients (103 with MFS and 65 with LDS). The prevalence of MAD was 41%. MAD was present in all age groups. Aortic events occurred in 112 (67%) patients (27 with dissections and 85 with prophylactic surgical interventions). Patients with MAD were younger at aortic event than those without MAD (log rank = 0.02) Patients with aortic events had greater MAD distance in posterolateral wall [8 (7-10) mm vs. 7 (6-8) mm, P = 0.04]. Mitral events occurred more frequently in patients with MAD (P < 0.001). CONCLUSION: MAD was highly prevalent in patients with MFS and LDS. MAD was a marker of severe disease including aortic events at younger age and need of mitral valve surgery. Screening patients with MFS an LDS for MAD may provide prognostic information and may be relevant in planning surgical intervention. Detection of MAD in patients with MFS and LDS may infer closer clinical follow-up from younger age.

Cerebral microemboli and brain injury during carotid artery endarterectomy and stenting.

BACKGROUND AND PURPOSE: Cerebral microembolic signals detected by transcranial Doppler are frequent during carotid angioplasty with stenting and carotid endarterectomy (CEA). Their potential harmful effects on the brain are, however, unclear. The aim of this study was to relate the frequency and type of per-procedural microembolic signals to procedure-related ipsilateral ischemic strokes and new ipsilateral ischemic lesions on diffusion-weighted cerebral MRI. METHODS: Eighty-five patients who were prospectively treated with CEA (61) or carotid angioplasty with stenting (30) for high-grade (>/=70%) internal carotid artery stenoses were monitored during the procedures using multifrequency transcranial Doppler with embolus detection and differentiation. Pre- and postprocedural cerebral diffusion-weighted cerebral MRIs were performed on a subset of patients. RESULTS: Solid and gaseous microemboli were independently associated with procedure-related ipsilateral ischemic strokes (solid: P=0.027, gaseous: P=0.037) or new ipsilateral diffusion-weighted cerebral MRI lesions (solid: P=0.043, gaseous: P=0.026). Microembolic signals were detected during all procedures except one (CEA); 17% and 21% of all emboli were solid during carotid angioplasty with stenting and CEA, respectively. Patients undergoing carotid angioplasty with stenting had more solid (P<0.001) and gaseous (P<0.001) emboli and more new ipsilateral ischemic strokes (P=0.033) compared with patients undergoing CEA. Echolucent plaques (P=0.020) and preprocedural diffusion-weighted cerebral MRI ischemic lesions (P=0.002) were associated with increased numbers of solid emboli. CONCLUSIONS: Solid and gaseous microemboli were increased in patients with procedure-related ipsilateral ischemic strokes or new diffusion-weighted cerebral MRI lesions, which suggests that both solid and gaseous emboli may be harmful to the brain during CEA and carotid angioplasty with stenting.

[Carotis stenosis-open surgery and endovascular treatment]. / Apen kirurgi og endovaskulaer behandling av carotisstenose.

BACKGROUND: Patients who have a carotid stenosis and suffer a TIA have a high risk of stroke shortly afterwards, and should be offered prophylactic surgery within 2 weeks. We present the results for treatment of carotid stenosis from Oslo University Hospital, Rikshospitalet in the period 2001-2008. MATERIAL AND METHODS: The material comprises all patients treated for carotid stenosis, with either carotid thrombendarterectomy (CEA) or endovascular stenting, in the period 2001-2008. All procedures were prospectively recorded in a database. A neurologist examines the patients before, and 1 and 12 months after treatment. RESULTS: 408 carotid stenoses were treated in the observation period. Median age (range) was 68 years (21-85), and 125 (31 %) patients were women. 206 (64.2 %) of the 321 stenoses treated with CEA were symptomatic as were 53 (61 %) of the 87 who underwent endovascular treatment (87). The rate of serious stroke and/or death within 30 days after CEA was 1.9 % for symptomatic stenoses and 1.1 % for asymptomatic stenoses; after endovascular treatment the corresponding numbers were 1.9 % and 3.8 %. INTERPRETATION: We have offered endovascular treatment to patients in whom surgery would be complicated (restenosis, radiation-induced stenosis etc). Results could therefore not be compared within our material. CEA prevents stroke, and it has been shown that the risk of complications is higher with stenting. Evaluation and treatment of patients with carotid stenosis should be included in the planned National guidelines for stroke treatment.

Current Medical and Surgical Stroke Prevention Therapies for Patients with Carotid Artery Stenosis.

Carotid Artery Stenosis (CAS) is a marker of systemic atherosclerosis and patients with CAS are at high risk of vascular events in multiple vascular locations, including ipsilateral ischemic stroke. Both medical and surgical therapies have been demonstrated effective in reducing this risk. The optimal management for patients with asymptomatic carotid artery stenosis remains controversial. In patients with symptomatic CAS ≥70%, CEA has been demonstrated to reduce the risk of stroke. With the risk of recurrent stroke being particularly high in the first 2 weeks after the first event, Carotid Endarterectomy (CEA) or carotid angioplasty with stenting provides maximal benefits to patients with symptomatic CAS ≥70% if performed within this «2-week¼ target. Several large ongoing trials are currently comparing the risks and benefits of carotid revascularization versus medical therapy alone.

Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis: possible role in inflammation and plaque destabilization.

BACKGROUND: Although the participation of inflammation in atherogenesis is widely recognized, the identification of the different components has not been clarified. In particular, the role of inflammation in plaque destabilization is not fully understood. METHODS AND RESULTS: Our main findings were as follows: (1) In a microarray experiment, we identified visfatin, one of the most recently identified adipokines, as a gene that was markedly enhanced in carotid plaques from symptomatic compared with plaques from asymptomatic individuals. This finding was confirmed when carotid plaques from 7 patients with asymptomatic and 14 patients with symptomatic lesions were examined with real-time reverse transcription polymerase chain reaction. (2) Immunohistochemistry showed that visfatin was localized in areas that were rich in lipid-loaded macrophages. (3) The relationship between visfatin and unstable lesions was also found in patients with coronary artery disease, demonstrating a strong visfatin immunostaining in lipid-rich regions within the material obtained at the site of plaque rupture in patients with acute myocardial infarction. (4) Both oxidized low-density lipoprotein and tumor necrosis factor-alpha increased visfatin expression in THP-1 monocytes, with a particularly enhancing effect when these stimuli were combined. (5) Visfatin increased matrix metalloproteinase-9 activity in THP-1 monocytes and tumor necrosis factor-alpha and interleukin-8 levels in peripheral blood mononuclear cells. Both of these effects were abolished when insulin receptor signaling was blocked. CONCLUSIONS: Our findings suggest that visfatin should be regarded as an inflammatory mediator, localized to foam cell macrophages within unstable atherosclerotic lesions, that potentially plays a role in plaque destabilization.

Soluble CD36 in plasma is increased in patients with symptomatic atherosclerotic carotid plaques and is related to plaque instability.

BACKGROUND AND PURPOSE: The risk for cardiovascular events is related to the composition and stability of an atherosclerotic plaque driven by inflammation and deposition of lipids. Scavenger receptors are a family of cell surface receptors involved in lipid uptake and inflammation. Recently, we found that soluble CD36 is increased in plasma from patients with diabetes strongly correlated with insulin resistance. METHODS: We tested whether soluble CD36 is a marker of plaque stability in patients with high-grade internal carotid stenoses (n=62). The patients were classified according to plaque symptomatology and plaque echogenicity on ultrasound examination. RESULTS: When patients were divided into 3 groups according to the latest clinical symptoms from plaques (ie, symptoms within the last 2 months [n=16], symptoms within the last 2 to 6 months [n=15], or asymptomatic [n=31]), the former group had significantly raised plasma levels of soluble CD36 as compared with the other 2 groups. In contrast, we found no differences in plasma levels of C-reactive protein, beta-thromboglobulin, lipid parameters, or HbA1C between these groups. The patients with echolucent carotid plaques (n=20) tended to have higher soluble CD36 levels in plasma compared with those with echogenic/heterogenic plaque (n=39; P=0.087). By immunohistochemistry, CD36 was localized to macrophages-rich area of intima within the atherosclerotic lesion. CONCLUSIONS: We propose that sCD36 may be a marker of plaque instability and symptomatic carotid atherosclerosis, possibly at least partly as a result of CD36 release to the circulation from the foam cells within the atherosclerotic lesion.

Survival, causes of death, and cardiovascular events in patients with Marfan syndrome.

BACKGROUND: To explore survival, causes of death, and the prevalence of cardiovascular events in a Norwegian Marfan syndrome (MFS) cohort. MFS is a heritable connective tissue disorder associated with reduced life expectancy-primarily due to aortic pathology. METHODS: A follow-up study of 84 MFS adults, initially investigated in 2003-2004. In 2014-2015, 16 were deceased, 47 of 68 survivors consented to new clinical investigations. Analyses of events were performed for 47 survivors and 16 deceased at follow-up. Standardized mortality ratios (SMR), using the mortality rate of the Norwegian population as reference, were calculated for all 84 and calculated for men and women separately. Causes of death and information on cardiovascular events were retrieved from death certificates and medical records. RESULTS: Standardized mortality ratios (95% confidence interval): for the whole cohort: 5.24 (3.00-8.51); for men: 8.20 (3.54-16.16); for women: 3.85 (1.66-7.58). Cardiovascular causes were found in 11 of 16 deceased, eight of these related to aortic pathology. Cancer was the cause of death in three patients. At follow-up, 51% had new cardiovascular events; 59% had undergone aortic surgery. Men experienced aortic events at younger age than women. 32% of the survivors were not followed-up as recommended. CONCLUSION: Life expectancy is reduced in this MFS cohort compared to the Norwegian population. Cardiovascular complications develop throughout life, particularly aortic pathology, the major cause of death in MFS. Death and aortic pathology seem to occur earlier in men. There is a need to improve follow-up according to guidelines.

Increased Levels of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in Ischemic Stroke and Transient Ischemic Attack.

BACKGROUND: Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) has been shown to be increased in patients with acute ischemic stroke. Here, we evaluated plasma sLOX-1 levels and vascular carotid plaque LOX-1 (ie, OLR1) gene expression in patients with ischemic stroke and transient ischemic attack (TIA) with particular focus on their relation to time since symptom onset. METHODS AND RESULTS: Plasma sLOX-1 (n=232) and carotid plaque OLR1 gene expression (n=146) were evaluated in patients who were referred to evaluation for carotid endarterectomy, as well as in healthy control plasma (n=81). Patients were categorized according to presence of acute ischemic stroke or transient ischemic attack (n=35) ≤7 days, >7 days ≤3 months (n=90), >3 months (n=40), or no reported symptoms before study inclusion (n=67). Our major findings were the following: (1) Patients with carotid atherosclerosis had increased plasma sLOX-1 levels as compared with controls. (2) Plaque OLR1 mRNA levels were increased in carotid plaques (n=146) compared with nonatherosclerotic vessels (ie, common iliac arteries of organ donors, n=10). (3) There were no differences in sLOX plasma levels or OLR1 gene expression when analyzed according to the time since relevant cerebral ischemic symptoms. (4) Also patients with severe carotid atherosclerosis without any previous ischemic events had raised sLOX-1 levels. (5) Immunostaining showed colocalization between LOX-1 and macrophages within the carotid plaques. (6) Also patients with acute stroke (within 7 days) caused by atrial fibrillation (n=22) had comparable raised sLOX-1 levels. CONCLUSIONS: sLOX-1 levels are elevated in patients with ischemic stroke and transient ischemic attack independent of cause and time since the ischemic event.

[Operative and endovascular treatment of carotis stenosis--when is it indicated?]. / Operativ og endovaskulaer behandling av carotisstenose--når er det aktuelt?

BACKGROUND: Stroke is the most common cause of disability in Norway. Most strokes are ischemic, and 25-30% are caused by emboli from atherosclerotic plaques in pre-cerebral arteries. The aim of this study was to review the literature on effectiveness of stroke prevention by surgical and endovascular treatment of carotid bifurcation stenoses. MATERIAL AND METHODS: Search of the PubMed and Cochrane Library. Relevant textbook chapters and personal experience have also supported the evaluation. RESULTS AND INTERPRETATION: Prevention of stroke by carotid endarterectomy is documented in several large randomised controlled trials. For carotid stenoses with reduced diameters of more than 50%, a significant reduction of 5-year stroke risk is achieved with surgery and best medical treatment, compared to best medical treatment alone. The benefit is greatest with symptomatic stenoses, especially if surgery is performed shortly after onset of symptoms. Patients with transient ischemic attack (TIA), minor stroke or amaurosis fugax should without delay be referred to an ultrasound examination of the carotid. Surgery as soon as possible is indicated if > 70% stenosis is found, and for men also with moderate stenoses (50-69%). The benefit is less pronounced for women with moderate stenosis and they should be considered individually. In asymptomatic patients, surgery reduces the 5-year stroke risk from 11.8 to 6.4%. The indication for surgery in asymptomatic patients must be balanced against age, co-morbidity, and the quality of surgery at each centre. A low operative morbidity is a prerequisite. No comparable evidence exists for endovascular treatment, and it is recommended that patients eligible for stent treatment are included in ongoing randomised trials comparing stent treatment and endarterectomy.

Norwegian trends in numbers of lower extremity revascularisations and amputations including regional trends in endovascular treatments for peripheral arterial disease: a retrospective cross-sectional registry study from 2001 to 2014.

OBJECTIVE: The numbers of lower extremity revascularisations and amputations are insufficiently reported in Norway. To support future policy decisions regarding the provision of vascular treatment, knowledge of such trends is important. METHODS: This retrospective cross-sectional study from 2001 to 2014 used data from the Norwegian Patient Registry. The revascularisation treatments were categorised in multilevel, aortoiliac, femoral to popliteal and popliteal to foot levels and sorted as open, endovascular and hybrid. The sessions in amputations were divided in major (thigh and below knee) and minor (ankle, foot or digit). Incidence rates were assessed per 100 000 for patients in the age group >60 years. The diabetic prevalence was calculated and the endovascular numbers at the South-Eastern, Western, Central and Northern Norway Regional Health Authority were compared. RESULTS: The overall revascularisation rates increased from 308.7 to 366.8 (p=0.02). Open revascularisations decreased from 158.9 to 98.7 (p<0.01) while endovascular revascularisations increased from 142.2 to 243.4 (p<0.01). Hybrid revascularisations increased from 7.4 to 24.8 (p<0.01). Major amputation rates decreased from 87.8 to 48.7 (p<0.01) while minor amputations increased from 12.3 to 19.6 (p=0.01). The diabetic percentages increased from 12.2 to 22.3 (p<0.01) in revascularisations, from 26.5 to 30.8 (p=0.02) in major amputations and from 43.0 to 49.3 (p=0.13) in minor. (p values refer to average annual changes.) The regional trends in endovascular treatments varied within and between the vascular groups. CONCLUSION: From 2001 to 2014, the revascularisation rates increased due to the rise in endovascular procedures. Open revascularisations and major amputation rates decreased, minor increased. The regional variances in endovascular treatments indicate that the availability of this technology differed between the health regions of Norway. The increase in patients with diabetes requires continued awareness of diabetes and its complications.

Cardiovascular surgery in Loeys-Dietz syndrome types 1-4.

OBJECTIVES: The first publication of Loeys-Dietz syndrome (LDS) described aortic rupture at young ages. Experience with new LDS types showed that the clinical course varies, and thresholds for prophylactic surgery are discussed. As this is an uncommon disease, experience needs to be shared. METHODS: Retrospective review of patients with LDS types 1-4 undergoing cardiovascular surgery during the years 1991-2016. RESULTS: Thirty-five patients (including 6 children with LDS2) underwent 57 operations. LDS 1, 2, 3 and 4 included 4, 17, 11 and 3 patients, respectively. Mean age at first surgery was 36 years, with a non-significant trend that LDS2 patients were younger. Of the 9 emergency surgeries, 7 were type A dissections, with 1 postoperative death. Twenty-two patients had prophylactic aortic root surgery (17 valve-sparing root replacements), with 1 postoperative death, 1 reoperation with valve replacement and 1 late death. Freedom from root reintervention and death was 92% at 13 years. Of the 11 patients with LDS3, 5 needed mitral valve surgery. Mitral valve disease was not found in the other LDS types. Ten patients needed >1 operation. Of the 57 operations, 33 were in the ascending aorta, 20 in the aorta distal to the arch including branches and 4 were isolated heart surgeries. Of the 20 vascular operations, 16 were in LDS2. Cumulative survival 20 years after first surgery (all patients) was 94.3%. CONCLUSIONS: Clinical course seems to be more aggressive in LDS2, with index operation at a younger age, and higher risk of needing several operations. Vascular disease distal to the arch is not uncommon. LDS3 seems to be associated with mitral valve disease. Prophylactic aortic root surgery is safe and durable.