Reconstruction and functional analysis of altered molecular pathways in human atherosclerotic arteries

<p>Abstract</p> <p>Background</p> <p>Atherosclerosis affects aorta, coronary, carotid, and iliac arteries most frequently than any other body vessel. There may be common molecular pathways sustaining this process. Plaque presence and diffusion is revealed by circulating factors that can mediate systemic reaction leading to plaque rupture and thrombosis.</p> <p>Results</p> <p>We used DNA microarrays and meta-analysis to study how the presence of calcified plaque modifies human coronary and carotid gene expression. We identified a series of potential human atherogenic genes that are integrated in functional networks involved in atherosclerosis. Caveolae and JAK/STAT pathways, and S100A9/S100A8 interacting proteins are certainly involved in the development of vascular disease. We found that the system of caveolae is directly connected with genes that respond to hormone receptors, and indirectly with the apoptosis pathway.</p> <p>Cytokines, chemokines and growth factors released in the blood flux were investigated in parallel. High levels of RANTES, IL-1ra, MIP-1alpha, MIP-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-17, PDGF-BB, VEGF and IFN-gamma were found in plasma of atherosclerotic patients and might also be integrated in the molecular networks underlying atherosclerotic modifications of these vessels.</p> <p>Conclusion</p> <p>The pattern of cytokine and S100A9/S100A8 up-regulation characterizes atherosclerosis as a proinflammatory disorder. Activation of the JAK/STAT pathway is confirmed by the up-regulation of IL-6, STAT1, ISGF3G and IL10RA genes in coronary and carotid plaques. The functional network constructed in our research is an evidence of the central role of STAT protein and the caveolae system to contribute to preserve the plaque. Moreover, Cav-1 is involved in SMC differentiation and dyslipidemia confirming the importance of lipid homeostasis in the atherosclerotic phenotype.</p

Observe the Unexpected: A Strange History of Bioprosthesis in a Patient in Dialytic Treatment

A 73-year-old male with a history of right nephrectomy due to cancer in 1996 was referred to our hospital for dyspnea and acute chest pain. In May 2007, the Shelhigh® No-React® valved bioconduit was implanted using the Bentall-De Bono procedure due to the finding of severe aortic valve insufficiency and acute type A aortic dissection. Nine months after discharge, he was placed on chronic renal dialysis. The patient's condition was followed carefully after being placed on dialysis, and now, thirteen years later the implanted aortic valve is still moving freely without signs of calcification

Current results of endovascular repair of thoraco-abdominal aneurysms†.

OBJECTIVES Fenestrated and branch endografts represent a totally endovascular solution for high-risk patients with atherosclerotic thoraco-abdominal aortic aneurysms (TAAAs). This study reports the early outcome of endovascular TAAA repair. METHODS Interrogation of a prospective database of consecutive patients who underwent endovascular repair (EVAR) for TAAA between June 2007 and October 2012. RESULTS Sixty-two high-risk patients (55 men; median age 72, range 54-84 years) underwent fenestrated (n = 39) or branch (n = 23) EVAR for non-ruptured TAAA [extent I-III (n = 26) and IV (n = 36)]. Twenty patients had undergone 22 previous aortic procedures. A total of 221 target vessels (coeliac 50, superior mesenteric 61, renal 106, left subclavian 1 and hypogastric 3) were preserved with scallops (n = 17), fenestrations (n = 140) or branches (n = 62) and 201 of these vessels were stent-grafted (coeliac 34, superior mesenteric 58, renal 105, left subclavian 1 and hypogastric 3). The 30-day mortality was 1.6% (n = 1) and one further patient died on postoperative day 62 from respiratory complications. Spinal cord injury (SCI) developed in 5 (8%) patients (3 women and 2 men). Two patients required temporary renal replacement therapy and a further two commenced planned postoperative dialysis. CONCLUSIONS In high-risk patients with TAAA, fenestrated and branch EVAR is associated with low early mortality and requirement for renal support, but the risk of SCI is not insignificant despite the use of cerebrospinal fluid drainage and blood pressure manipulation. Our current practice is to stage the repair of extent I-III aneurysms and this has significantly reduced the incidence of SCI

Surgical myocardial revascularization in patients with reduced systolic left ventricular function

Surgical myocardial revascularization in patients with reduced left ventricular function has been a matter of debate for decades. Recently published 10-years extension follow-up of the STICH trial have conclusively demonstrated benefit of surgical myocardial revascularization in patients with significant coronary artery disease and low left ventricular ejection fraction. However, selection of patients for surgery remains challenging as well as decision to perform percutaneous rather than surgical revascularization in this class of patients. New evidence helped to clarify the role of preoperative patients' characteristics as risk factors for surgery and to identify those patients who may benefit the most from surgery. Focus of this review is to review epidemiology, aetiology and pathophysiology of coronary artery disease in patients with reduced left ventricular function, role of viability and results of observational and investigational studies on revascularization in patients with reduced left ventricular function with a particular emphasis on relative indication of coronary artery bypass grafting and percutaneous coronary intervention and the surgical implications of development of ischemic mitral regurgitation or ischemic left ventricular aneurysm

Open surgical replacement of the descending thoracic and thoracoabdominal aorta in patients with confirmed Marfan and Loeys-Dietz syndromes:A 20-year single-centre experience

OBJECTIVES: A relatively small proportion of patients with heritable thoracic aortic disease require open surgical replacement of the distal thoracic aorta. We reviewed the outcome in patients with Marfan and Loeys-Dietz syndromes treated in an aortic centre in the United Kingdom.METHODS: We performed a single-centre retrospective study of consecutive patients treated between October 1999 and December 2019. The primary end point was 30-day mortality. Secondary end points were Kaplan-Meier estimates of medium-term survival and freedom from distal reintervention. Data are presented as median (interquartile range).RESULTS: A total of 58 patients [33 men; 51 with Marfan syndrome; median age 41 years (35-48); median aneurysm diameter 60 mm (55-74)] underwent open descending (n = 21) or thoracoabdominal aortic replacement (n = 37). All repairs were performed using cardiopulmonary bypass with hypothermic circulatory arrest in 31 patients. The 30-day mortality was 5.2% (n = 3, including 2 patients ≥ 60 years with significant comorbidity). Major non-fatal complications included early reoperation (n = 7), tracheostomy (n = 9), temporary renal replacement therapy (n = 3), permanent spinal cord deficit (n = 2) and permanent stroke (n = 1). Median follow-up was 81 months (48-127). Estimated (±standard error) 5-year survival was 85% ±5%. Seven patients had distal aortic reintervention with no deaths or spinal cord deficit: estimated 5-year freedom from distal reintervention was 94% ±3%. There was no difference in survival or freedom from distal reintervention comparing: elective vs. non-elective; type of heritable thoracic aortic disease; DeBakey type; or extent of surgical repair.CONCLUSIONS: Descending thoracic and thoracoabdominal aortic replacement in patients with heritable thoracic aortic disease can be performed with low perioperative morbidity and mortality, satisfactory long-term survival and low requirement for distal reintervention.</p

Clinical presentation is the main predictor of in-hospital death for patients with acute type a aortic dissection admitted for surgical treatment: A 25 years experience.

Background: This retrospective analysis assessed the hypothesis that clinical status on admission more than other variables related to surgicalor post-operative management may influence in-hospital mortality after surgical treatment of acute type A aortic dissection.Methods: Between January 1979 and April 2004, 311 patients, mean age of 59.5±13 years (range, 18 to 88 years), with acute type A aorticdissection were referred for surgery. Logistic regression analysis was applied to demographics, etiological, clinical, and surgical variables, toidentify independent predictors of in hospital death.Results: In hospital mortality rate was 23%. Univariate analysis showed older age (p=0.03, OR1.02/yrs), cardiac tamponade (p=0.001; OR2.43), hypotension (p=0.0001; OR 8), myocardial ischemia (p=0.005; OR 7), acute renal failure (p=0.0001; OR 4.16), limb ischemia(p=0.0002; OR 3.3), neurological deficits pre-op (p=0.0001; OR 8.5), and mesenteric ischemia (p=0.003) as independent predictors of inhospitaldeath. Multivariate analysis identified the following presenting variables as predictors of in-hospital death: hypotension (p=0.003;OR 7.4), myocardial ischemia (p=0.03; OR 5.8), mesenteric ischemia (p=0.009), acute renal failure (p=0.0001; OR 3.9), neurologicaldeficits (p=0.0001; OR 7.7). In-hospital mortality for the group of patients presenting with at least one of the tested pre-operativecomplications (N=158; 51%) was 33% vs 12% (p=00001). No other variables emerged as significant for in-hospital death.Conclusion: In an era of standardized surgical technique, expeditious referral and intervention by lowering preoperative dissection-relatedcomplications and co-morbidities might represent the most efficacious tool to improve results

Endovascular Repair of Acute Thoraco-abdominal Aortic Aneurysms.

OBJECTIVES The outcome of endovascular repair (EVAR) for acute thoraco-abdominal aortic aneurysm (TAAA) is reported and the applicability of the t-Branch off the shelf (OTS) device is determined. METHODS Interrogation of a prospectively maintained database identified all patients who underwent EVAR for acute TAAA between September 2012 (when the first non-elective t-Branch case was performed) and November 2015. Early and medium-term outcomes were analysed. Survival and re-intervention-free survival were calculated by Kaplan-Meier analysis. RESULTS A total of 39 patients (27 men; mean ± SD age, 72 ± 8 years) were treated for acute symptomatic (n = 29) or ruptured (n = 10) TAAA (20 anatomical extent I-III, 19 extent IV). Fourteen patients had mycotic aneurysms. The mean aneurysm diameter was 80 ± 20 mm. The mean ± SD follow-up was 21.4 ± 15.4 months. Surgeon modified fenestrated EVAR was used in 24 patients, chimney/periscope EVAR in two, and t-Branch in 13 (33%) patients. Aortic coverage was greater than 40 mm above the coeliac axis in all patients. A total of 127 target vessels (TVs) were preserved (mean 3.3 per patient) and two occluded within 30 days. The 30 day mortality was 26%. Four (10%) patients developed spinal cord ischaemia (SCI): two with paraplegia died within 30 days, and two with paraparesis recovered completely with blood pressure manipulation and cerebrospinal fluid drainage. Estimated overall survival (±SD) at 12 and 24 months was 71.8 ± 7.2% and 63.2 ± 7.9%, respectively. Estimated freedom from re-intervention at 12 and 24 months was 93 ± 4.8% and 85.3 ± 6.8%, respectively. CONCLUSIONS EVAR for acute TAAA is associated with acceptable early and mid-term results in patients who have no other treatment options. Only one third of these patients were suitable for the t-Branch device, indicating that further advances in device design are required to treat the majority of acute TAAA patients with commercially available OTS technology

Open aortic arch replacement in high-risk patients: the gold standard†.

OBJECTIVES Open total aortic arch replacement (TAR) in high-risk patients is considered by some to be associated with a prohibitively perioperative risk. Recent reports describe hybrid techniques to treat this group. We reviewed our outcomes of open surgery in a 'high-risk' group of patients. METHODS All patients who underwent open TAR between 2000 and 2013 were identified from our prospectively maintained database. Patients comparable with the ones who underwent hybrid repair in previous studies (logistic EuroSCORE between 20 and 60 without intervention on the aortic root or on the mitral/tricuspid valve) were selected for analysis. RESULTS Fifty-eight patients were identified. Median logistic EuroSCORE was 27.4 (range 20-57) and median age was 76 years (34.5% male). There were 11 resternotomies (18.9%) and 20 procedures were urgent/emergency (34.5%). Preoperative comorbidities included chronic obstructive pulmonary disease (31%), coronary artery disease (22.4%), peripheral vascular disease (48.3%), previous stroke (5.2%), previous myocardial infarction (3.4%) and left ventricular dysfunction (12%). Concomitant procedures included aortic valve replacement/resuspension (58.7%), coronary artery bypass grafting (22.4%), open descending aorta replacement (10.3%) and frozen elephant trunk (19%). Overall in-hospital mortality, permanent stroke and spinal cord injury rate were 6.9, 1.7 and 0%, respectively. There were no deaths or stroke in the elective group. One-year, 5-year and 10-year estimates of survival were 82.7, 70.0 and 37.8%, respectively. CONCLUSIONS Open TAR can be performed with low mortality and morbidity and excellent long-term results even in high-risk patients. Total endovascular repair may represent an option for patients not suitable for open surgery

[Follow-up after surgical treatment of type A acute aortic dissection: current evidence and controversies]

Type A acute aortic dissection (TA-AAD) is a catastrophic condition for which emergency surgery is the mainstay of therapy. Surgical treatment of TA-AAD is centered on excision of the proximal intimal tear, replacement of the ascending aorta and re-establishment of a dominant flow in the distal true lumen. In patients who survive surgery, a dissected distal and/or proximal aorta remains, posing a risk of subsequent aneurysmal degeneration, rupture and malperfusion, and secondary extensive interventions are often required. However, knowledge regarding the risk factors of progression of residual aortic dissection is limited, and no well-defined recommendations for clinical and imaging follow-up have been generated thus far. The aim of this paper is to review and discuss on the current evidence and controversies on the long-term management of patients operated on for TA-AAD

Aortic diameter remodelling after the frozen elephant trunk technique in aortic dissection: Results from an international multicentre registry

OBJECTIVES: The frozen elephant trunk (FET) technique allows one-stage hybrid repair approach in aortic dissection (AoD). Even if the effect of the FET technique on promoting false lumen (FL) thrombosis has been proved in the past, the relative importance of FL thrombosis on aortic remodelling at different levels of the distal aorta and the magnitude of this effect is not well known. The aim of the study was to evaluate aortic remodelling following a FET technique for AoD. METHODS: A multicentre international registry database was searched to identify all patients who underwent a FET procedure for an AoD. A total of 383 patients with AoD were operated on between January 2005 and March 2014 with the FET technique; 137 patients (65 acute AoD and 72 chronic AoD) who survived the initial repair with at least a 1-year follow-up CT scan were included in the study. RESULTS: The rate of FL thrombosis was higher in the mid-descending thoracic aorta (99.3%) and lower in the distal abdominal aorta (13.9%) but similar between acute and chronic AoDs. The negative remodelling rate was similar between acute and chronic AoDs in the abdominal aorta, but chronic AoD exhibited a higher rate of negative remodelling in the descending thoracic aorta (33% vs 17.5%, P = 0.040). CONCLUSIONS: The FET technique provides an effective treatment for AoD, promoting FL thrombosis and remodelling in the descending thoracic aorta. Changes in the diameter of the aortic lumen depend mainly on the status of the FL and are similar between acute and chronic AoD. Changes in the diameter of true lumen are affected by both the FL status and the timing of the presentation. However, increased FL thrombosis and positive remodelling rates are not maintained at the level of the abdominal aorta, and strict follow-up is mandatory to detect early changes in the aortic dimensions, which may warrant further interventions