Treatment of Aortoiliac Occlusive Lesions by Aortic Robotic Surgery: Learning Curve and Midterm Outcome.

BACKGROUD: The learning curve and midterm results of aortoiliac occlusive disease (AIOD) revascularization by robot-assisted laparoscopic (RAL) surgery may be known. METHODS: A prospective single-center study was conducted in the vascular surgery department of Georges Pompidou European Hospital (Paris, France). Patients with AIOD treated by RAL from February 2014 to February 2019 were included. Demographic characteristics, past medical history, Trans-Atlantic Inter-Society Consensus (TASC) lesions classifications, mortality, primary and secondary patency, as well as complication rates were collected. Safety was analyzed by the cumulative sum control chart method with a conversion rate of 10%, operative time by cumulative average-time model, and primary and secondary patency by the Kaplan-Meier method. RESULTS: Seventy patients were included, 18 (25.7%) with TASC C lesions and 52 (74.3%) with TASC D lesions. Before discharge, 14 (24.3%) patients had surgical complications. Among them, 10 (14.3%) required at least one reintervention. One (1.4%) patient died during the hospitalization. The learning curve in terms of safety (conversion rate) was 13 cases with an operating time of 220 minutes after 35 patients. During follow-up (median 37 months [21; 49]), 63 patients (91.3%) improved their symptoms, 53 (76.8%) became asymptomatic, and 3 graft limb occlusions occurred. The primary patency at 12, 24, 36, and 48 months was 94%, 92%, 92%, and 92%, respectively, while the secondary patency for the same intervals was 100%, 98.1%, 98.1%, and 98.1%, respectively. CONCLUSIONS: Robotic surgery in AIOD revascularization seems safe and effective; allowing to treat patients with few comorbidities and severe lesions, in a dedicated center experienced in RAL, with excellent patency. Prospective clinical trials should be performed to confirm safety.

Thoracic Endovascular Repair after Total Aortic Arch Replacement with Frozen Elephant Trunk for Type a Aortic Dissection.

BACKGROUND: The management of residual aortic dissection after initial type A repair with the Frozen elephant trunk technique remains mostly unexplored. This work aimed to evaluate endovascular second-stage surgery for patients with residual aortic dissection. METHODS: A retrospective analysis of consecutive patients that underwent Type A aortic repair with Frozen elephant trunk, followed by a second-stage endovascular procedure was done from March 2016 to December 2021. The primary outcome was aortic-related adverse events or mortality, and secondary outcomes were aortic remodeling and perioperative complications. Remodeling was assessed by comparing the difference in ratios for true lumen/total aortic diameters on pre-operative and follow-up scans. RESULTS: Thirty-four patients underwent second-stage surgery after Type A repair during the study period (7 thoracic endovascular aortic repair extensions, 1 STABLE/PETTICOAT, and 26 STABILISE). Median follow-up was 23 months (range 2-66 months). There were no perioperative deaths or major complications and 1 reoperation for left subclavian re-embolization. At the last follow-up, there was no aortic-related mortality. There were 5 aortic-related adverse events, including another subclavian re-embolization and a preplanned open conversion. Risk factors were connective tissue disorders (P = 0.01) and aortic aneurysms >55 mm (P = 0.03). Distal remodeling reached statistical significance in all segments (P < 0.01) and was greater for patients treated with the STABILISE technique when compared to extended thoracic endovascular aortic repair (P = 0.01). CONCLUSIONS: Second-stage endovascular management of residual aortic dissection after initial Frozen elephant trunk repair showed excellent perioperative and good midterm outcomes and induced significant remodeling of the entire aorta in most cases, particularly with the STABILISE procedure.

Blunt Traumatic Aortic Injury Management, a French TraumaBase Analytic Cohort.

OBJECTIVE: Blunt traumatic aortic injury (BTAI) in severe trauma patients is rare but potentially lethal. The aim of this work was to perform a current epidemiological analysis of the clinical and surgical management of these patients in a European country. METHODS: This was a multicentre, retrospective study using prospectively collected data from the French National Trauma Registry and the National Uniform Hospital Discharge Database from 10 trauma centres in France. The primary endpoint was the prevalence of BTAI. The secondary endpoints focused chronologically on injury characteristics, management, and patient outcomes. RESULTS: 209 patients were included with a mean age of 43 ± 19 years and 168 (80%) were men. The calculated prevalence of BTAI at hospital admission was 1% (162/15 094) (BTAI admissions/all trauma). The time to diagnosis increased with the severity of aortic injury and the clinical severity of the patients (grade 1: 94 [74, 143] minutes to grade 4: 154 [112, 202] minutes, p = .020). This delay seemed to be associated with the intensity of the required resuscitation. Sixty seven patients (32%) received no surgical treatment. Among those treated, 130 (92%) received endovascular treatment, 14 (10%) open surgery (two were combined), and 123 (85%) were treated within the first 24 hours. Overall mortality was 20% and the attributed cause of death was haemorrhagic shock (69%). Mortality was increased according to aortic injury severity, from 6% for grade 1 to 65% for grade 4 (p < .001). Twenty-six (18.3%) patients treated by endovascular aortic repair had complications. CONCLUSION: BTAI prevalence at hospital admission was low but occurred in severe high velocity trauma patients and in those with a high clinical suspicion of severe haemorrhage. The association of shock with high grade aortic injury and increasing time to diagnosis suggests a need to optimise early resuscitation to minimise the time to treatment. Endovascular treatment has been established as the reference treatment, accounting for more than 90% of interventional treatment options for BTAI.

Thrombosis of Medium-Sized and Large Arteries During Covid-19 Infection: Results of the COVIVASC Study.

BACKGROUND: COVID-19 infection is associated not only with venous thromboses but also with arterial thromboses (COV-ATs) in relation with an endothelial dysfunction, a coagulopathy and rhythm disorders. The incidence, the topography, and the prognosis of COV-ATs remain poorly known. The objective of this study was to report the overall experience of the Greater Paris University Hospitals (Assistance Publique - Hopitaux de Paris, AP-HP) during the first pandemic wave of COVID-19 infection. METHODS: After approval by the ethics committee, a study using the AP-HP clinical data warehouse was carried out between March and May 2020. Overall, 124,609 patients had a polymerase chain reaction for COVID-19 in our hospitals, of which 25,345 were positive. From 20,710 exploitable stays, patients tested positive for COVID who presented an episode of acute COV-AT (except coronary and intracranial arteries) were selected on the basis of the French medical classification for clinical procedures codes. The data are presented as absolute values with percentages and/or means with standard deviation. RESULTS: Over the studied period, 60 patients (aged 71±14 years, 42 men) presented a COV-AT at the time of their hospitalization, an incidence of 0.2%. The arterial complication occurred 3±7 days after the COVID infection and was inaugural in 30% of the cases (n = 18). The sites of COV-AT were the lower extremities (n = 35%, 58%), the abdominal aorta (n = 10%, 17%), the thoracic aorta (n = 7%, 12%), the upper limbs (n = 7%, 12%), the cerebral arteries (n = 7%, 12%), the digestive arteries (n = 6%, 10%), the renal arteries (n = 2%, 3%), and the ophthalmic artery (n = 1%, 2%). Multiple COV-ATs were observed in 13 patients (22%). At the time of diagnosis, 20 (33%) patients were in intensive care, including six (10%) patients who were intubated. On computed tomography angiography, COVID lesions were classified as moderate and severe in 25 (42%) and 21 (35%) cases, respectively. Revascularization was attempted in 27 patients (45%), by open surgery in 16 cases, using endovascular techniques in 8 cases and with a hybrid approach in three cases. Six patients (22%) required reinterventions. The duration of hospitalization was 12±9 days. Early mortality (in-hospital or at 30 days) was 30% (n = 18). Nine (15%) patients presented severe nonlethal ischemic complications. CONCLUSIONS: Arterial involvement is rare during COVID-19 infection. The aorta and the arteries of the limbs are the privileged sites. The morbi-mortality of these patients is high. Future studies will have to determine if the systematization of anticoagulation therapy decreases the incidence and the severity of the condition.

Mycobacterium bovis infection of an aortobifemoral bypass graft with Streptococcus intermedius superinfection after intravesical bacillus Calmette-Guérin immunotherapy for bladder cancer.

BACKGROUND: The Bacillus Calmette-Guerin (BCG) is a life-attenuated form of Mycobacterium bovis widely used as immunotherapy for localized bladder cancer. Adverse reactions to intravesical BCG instillations are rare. CASE: We describe a 70-year-old man with a history of an aortobifemoral bypass graft, placement of a synthetic mesh for treatment of a ventral hernia and, most recently, superficial bladder cancer treated with BCG therapy. Ten months after his final intravesical BCG instillation, he complained of fever and asthenia. After 12 months of investigation, he was diagnosed with Mycobacterium bovis infection of his aortobifemoral bypass graft and abdominal mesh, with Streptococcus intermedius superinfection. The bypass graft was excised and replaced with an in situ arterial allograft, the abdominal mesh was removed, and treatment started with amoxicillin, isoniazid, rifampicin and ethambutol. Several additional vascular interventions were needed for allograft degradation, but 12 months after the final procedure, outcome was good. DISCUSSION AND CONCLUSIONS: Among 35 cases of mycotic aneurysm reported after BCG therapy in the last 10 years, only one involved a vascular prosthesis. Surgical repair of such aneurysms using prosthetic grafts is commonly performed, associated with anti-mycobacterial treatment. Prognosis is poor with mortality of 14% (4/35) and a 26% rate of aneurysm recurrence under treatment (9/35).

Wall Shear Stress Measurement by Ultrafast Vector Flow Imaging for Atherosclerotic Carotid Stenosis.

OBJECTIVE: Carotid plaque vulnerability assessment could guide the decision to perform endarterectomy. Ultrafast ultrasound imaging (UF) can evaluate local flow velocities over an entire 2D image, allowing measurement of the wall shear stress (WSS). We aimed at evaluating the feasibility of WSS measurement in a prospective series of patients with carotid stenosis. METHODS: UF acquisitions, performed with a linear probe, had an effective frame rate of 5000 Hz. The flow velocity was imaged over the entire plaque area. WSS was computed with the vector field speed using the formula: with the blood velocity and µ, the blood viscosity. The WSS measurement method was validated using a calibrated phantom. In vivo, WSS was analyzed in 5 areas of the carotid wall: common carotid artery, plaque ascent, plaque peak, plaque descent, internal carotid artery. RESULTS: Good correlation was found between in vitro measurement and the theoretical WSS values (R2 = 0.95; p < 0.001). 33 patients were prospectively evaluated, with a median carotid stenosis degree of 80 % [75-85]. The maximum WSS value over the cardiac cycle follows the shape of the plaque with an increase during the ascent, reaching its maximum value of 3.25 Pa [2.26-4.38] at the peak of the plaque, and a decrease after passing of the peak (0.93 Pa [0.80-1.19]) lower than the WSS values in the non-stenotic areas (1.47 Pa [1.12-1.77] for the common carotid artery). CONCLUSION: UF allowed local and direct evaluation of the plaque's WSS, thus better characterizing local hemodynamics to identify areas of vulnerability. KEY POINTS: · Ultrafast vector Doppler allows calculation of the wall shear stress (WSS) by measuring velocity vectors over the entire 2D image.. · The setup to measure the WSS has been validated in vitro on a linear flow phantom by comparing measurements to in silico calculations.. · Applying this method to carotid plaque allows us to better describe the hemodynamic constraints that apply along the entire length of the plaque..

Using the OUTBACK Catheter to Overcome Aortic Reentry Issues in Retrograde Open Mesenteric Stenting.

BACKGROUND: The purpose of this study was to describe the use of the OUTBACK catheter to overcome aortic reentry issues in acute mesenteric ischemia (AMI) treated by retrograde open mesenteric stenting (ROMS). TECHNIQUE: The technique is demonstrated in two female patients presenting with late AMI related to flush occlusion of the superior mesenteric artery (SMA). In such cases of thrombotic AMI with clear preoperative evidence of intestinal necrosis, ROMS is the first-line revascularization technique in our intestinal stroke center. Following an open approach of the SMA through laparotomy, the SMA was punctured in a retrograde fashion. Retrograde mesenteric subintimal recanalization was initiated. In case of aortic reentry issue, the OUTBACK Elite (Cordis, Hialeah, Fl) catheter was advanced through the occlusion over a 0.014 guidewire. The aortic reentry was created by puncture of the aortic wall with the OUTBACK needle, positioned in the desired position. After low-profile balloon angioplasty of the reentry site and 0.035 guidewire exchange, ROMS was performed using balloon-expandable covered stent. CONCLUSIONS: The OUTBACK catheter appears to be a safe and effective tool to overcome aortic reentry issues in ROMS. This technical tip might therefore increase the technical success rate of challenging ROMS and decrease the need for bailout bypass in the septic context of AMI.

Autophagy is required for endothelial cell alignment and atheroprotection under physiological blood flow.

It has been known for some time that atherosclerotic lesions preferentially develop in areas exposed to low SS and are characterized by a proinflammatory, apoptotic, and senescent endothelial phenotype. Conversely, areas exposed to high SS are protected from plaque development, but the mechanisms have remained elusive. Autophagy is a protective mechanism that allows recycling of defective organelles and proteins to maintain cellular homeostasis. We aimed to understand the role of endothelial autophagy in the atheroprotective effect of high SS. Atheroprotective high SS stimulated endothelial autophagic flux in human and murine arteries. On the contrary, endothelial cells exposed to atheroprone low SS were characterized by inefficient autophagy as a result of mammalian target of rapamycin (mTOR) activation, AMPKα inhibition, and blockade of the autophagic flux. In hypercholesterolemic mice, deficiency in endothelial autophagy increased plaque burden only in the atheroresistant areas exposed to high SS; plaque size was unchanged in atheroprone areas, in which endothelial autophagy flux is already blocked. In cultured cells and in transgenic mice, deficiency in endothelial autophagy was characterized by defects in endothelial alignment with flow direction, a hallmark of endothelial cell health. This effect was associated with an increase in endothelial apoptosis and senescence in high-SS regions. Deficiency in endothelial autophagy also increased TNF-α-induced inflammation under high-SS conditions and decreased expression of the antiinflammatory factor KLF-2. Altogether, these results show that adequate endothelial autophagic flux under high SS limits atherosclerotic plaque formation by preventing endothelial apoptosis, senescence, and inflammation.

Mid-term Outcomes of Stent Assisted Balloon Induced Intimal Disruption and Relamination in Aortic Dissection Repair (STABILISE) in Acute Type B Aortic Dissection.

OBJECTIVES: This article reports mid-term results of 41 patients treated by the stent assisted balloon induced intimal disruption and relamination (STABILISE) technique for acute type B aortic dissection. METHODS: Between November 2011 and November 2017, 41 patients (10 male; median age 50 years) underwent proximal descending aortic stent grafting plus stent assisted balloon induced intimal disruption of the thoraco-abdominal aorta for acute type B aortic dissection. Serial computed tomography angiography was used to assess aortic remodelling. RESULTS: There were no intra-procedural complications. Fifteen branch arteries supplied by the false lumen were stented (9% of the visceral branch arteries). The thirty day incidence of death, stroke, and paralysis/visceral ischaemia was 2% (n = 1), 0%, 5% (n = 2), and 2% (n = 1) respectively. During a median follow up of 12 months (range 1-168) eight patients (20%) required re-intervention. Primary visceral stent patency was 93% (n = 14). No aortic related deaths occurred. On the most recent computed tomography angiogram, complete false lumen obliteration and aortic remodelling was obtained in all patients at the thoraco-abdominal level, and in 39% (n = 16) at the unstented infrarenal aorto-iliac level. The maximum aortic diameter increased in only two patients (5%) at the unstented infrarenal level. CONCLUSION: To obtain immediate and durable thoraco-abdominal aortic remodelling in acute type B dissections, the STABILISE technique is safe and reproducible while not compromising the patency of collateral branches.

Experimental Evaluation of Endovascular Fenestration Scissors in an Ovine Model of Aortic Dissection.

OBJECTIVE/BACKGROUND: To evaluate the experimental feasibility of endovascular fenestration using specific endovascular scissor prototypes in an ovine model of acute aortic dissection (AD). METHODS: A previously described endovascular technique was used to create a model of acute type B AD in sheep. Endovascular fenestrations using either endovascular scissor prototypes or a long sheath were compared. Four prototypes of endovascular fenestration scissors were evaluated. Both validity of the experimental model of AD and technical success of endovascular fenestration were assessed by haemodynamic criteria, completion angiography, transesophageal echocardiography, and post-procedural analysis of harvested aortas. RESULTS: Experimental acute AD was created by endovascular means in 17 sheep, with a technical success rate of 82%. Systolic blood pressure was lower in the false lumen than in the true lumen (58 ± 5 vs. 79 ± 3 mmHg, respectively; p < .001). Endovascular fenestration was performed in 11 models (endovascular scissors n = 8; long sheath n = 3). Controlled endovascular fenestration was obtained by the use of endovascular scissors (n = 5/8), resulting in a significant rise in false lumen systolic blood pressure after fenestration (60 ± 2 vs. 67 ± 9 mmHg before and after fenestration, respectively; p < .047). Long sheath fenestration resulted in an uncontrolled flap motion, leading to either pseudo-coarctation syndrome or aortic rupture (58 ± 6 vs. 40 ± 2 mmHg before and after fenestration, respectively; p < .001). CONCLUSION: In this experimental study, a reproducible AD model has been developed in sheep using endovascular procedures exclusively to evaluate endovascular fenestration techniques. Endovascular fenestration using a long sheath appeared hazardous and risky in vivo. Endovascular scissors constitute a dedicated and suitable tool to perform a safe controlled and effective endovascular fenestration in an ovine model.

Postmortem Retrieval of Arterial Allografts: Preliminary Results.

BACKGROUND: Cryopreserved arterial allografts are vascular substitutes used for arterial reconstructions in a septic field. Their use remains however limited by the shortage of donors. One of the possibilities to address this lack of grafts is to multiply the sources of retrieval. The objective of this preliminary study was the evaluation of the early clinical results and the microbiological safety of arterial grafts retrieved after death. METHODS: In addition to the standard conditions of arterial sampling, the criteria of inclusion for postmortem retrieval comprised the refrigeration of the body of the donor within 4 hr following the death, a 24-hr time limit from the death, and the availability of an adapted place for retrieval (surgical unit or death chamber respecting the required aseptic conditions). We only retrieved the femoral axes (FAs) and the aortoiliac bifurcation. The conditions of retrieval, transportation, preparation, and conservation were identical to those of cryopreserved arterial allografts harvested during standard multiple organs retrieval. We evaluated the bacteriological risk of contamination and the patency of the grafts in the short and medium term. RESULTS: In 2015 and 2016, 6 donors were included. Eleven FAs and 2 aortic bifurcations were harvested. The bacteriological samples done on arrival in bank and after thawing were negative in the 6 donors, but one of the 6 donors presented a bacterial contamination of other removed tissues, and the arterial grafts obtained from this donor were destroyed as a precaution (3 grafts). The quality of the grafts evaluated by the surgeon during harvesting was good in all the cases. The indications of allografts were arterial reconstruction in a septic field (n = 8) and aorto-hepatic bypass during hepatic transplantation (n = 1). One graft was unhopefully thawed without being used. At the end of the follow-up, 8 out of 9 grafts were patent. Two ruptures occurred in a context of locally persistent sepsis (crural abscess due to Salmonella typhi and persistent groin wound disunion with a polymicrobial flora). One allograft thrombosis was observed (aorto-hepatic bypass for transplantation). These complications were unrelated to the mode of graft harvesting. No aneurysmal evolution was observed. CONCLUSIONS: The preliminary results of this protocol are encouraging because the immediate quality of the grafts was good with a risk of microbiological contamination identical with that of the usual harvesting mode. This mode of harvesting looks promising to reduce the shortage in arterial allografts and could be extended to harvest thoracic aortic allografts. However, results at a larger scale are necessary to confirm these data.

Crossed pulmonary arteries as additional cause of dysphagia in association with right aortic arch and Kommerell diverticulum.

We describe an uncommon association of crossed pulmonary arteries and a right aortic arch with a Kommerell diverticulum and a left ligamentum arteriosum, resulting in disabling dysphagia in a 33-year-old woman. First, endovascular exclusion of the Kommerell diverticulum was performed using a thoracic stent graft, associated with left subclavian-carotid transposition. Second, open aneurysmorrhaphy and division of the left ligamentum arteriosum allowed a proper release of the oesophageal compression. Dysphagia completely disappeared in the postoperative course. Control computed tomography angiography at 6-month follow-up showed a satisfactory hybrid repair. A complete understanding of the combined effects of these two anatomical variations on oesophageal compression led to a suitable surgical management.

Technical Aspects of Open Repair for Degenerative Aneurysmal Evolution Despite Early Thoracic Endovascular Repair of Type B Aortic Dissection.

BACKGROUND: Closure of the proximal tear by thoracic endovascular aortic repair (TEVAR) at the acute phase appears to be a safe effective treatment to prevent aneurysmal degeneration type B dissection. However, it appears to be inefficient in up to a third of the patient. We report the technical aspects of our experience with patients undergoing secondary open repair after TEVAR for dissecting thoracoabdominal aneurysm despite early closure proximal tear by TEVAR. METHODS: During a period of 5 years, 96 patients presenting acute type B aortic dissections were treated by TEVAR and followed-up in our institution. Among them, 5 patients experienced an evolution to a dissecting thoracoabdominal aortic aneurysm. Their demographic data and initial medical conditions, delay to reintervention, operative technical details, perioperative and mid-term outcomes were collected and analyzed. RESULTS: All 5 patients (4 male, mean age 58 ± 9) were operated under peripheral normothermic bypass without deep circulatory arrest using the thoracic stent graft as an elephant trunk for completion of the proximal anastomosis. In cases of patency, the false lumen was reapproximated in the anastomosis, 6 visceral arteries were revascularized selectively. One patient died at day 1 of perioperative ventricular fibrillation due to an acute myocardial infarction. The 4 others are alive without complication after a median of 30 months, range (13-22). CONCLUSIONS: In our experience, TEVAR was not only efficient at the acute phase to deal with complications, but in cases of subsequent aneurysmal evolution, it made open repair even easier by avoiding very proximal cross-clamping/anastomosis and circulatory arrest.

Phlegmasia Cerulea Dolens as an Unusual Presentation of Ruptured Abdominal Aortic Aneurysm into the Inferior Vena Cava.

The aim of this case study is to report a case of unusual manifestation of ruptured abdominal aortic aneurysm (AAA) involving an aortocaval fistula (ACF) as phlegmasia cerulea dolens (PCD). A 58-year-old male presented with acute signs of PCD of the right lower limb, confirmed on duplex ultrasonography. Computed tomography angiography revealed a 65-mm ruptured AAA with a large ACF. Successful emergent surgical repair was performed, using implantation of an aortobi-iliac graft with primary closure of the fistula and associated venous thrombectomy. PCD revealing a ruptured AAA with ACF is rare. Knowledge of this original entity might be the most important factor on the outcome.

Management of Vascular Trauma during the Paris Terrorist Attack of November 13, 2015.

BACKGROUND: On November 13, 2015, Paris and Saint-Denis were the targets of terrorist attacks. The Public Hospitals of Paris Organization and the Percy Armed Forces Instruction Hospitals were mobilized to face the mass casualty situation. The objective of this study is to analyze the management of the victims presenting with a nonthoracic vascular trauma (NTVT). METHODS: All the data relating to the victims of NTVT who required a specific vascular open or endovascular treatment were analyzed retrospectively. A 6-month follow-up was obtained for all the patients. RESULTS: Among the 351 wounded, 20 (5.7%) patients had an NTVT and were dispatched in 8 hospitals (11 men of average age 32). NTVTs were gunshots in 17 cases (85%) or due to a handmade bomb in 3 cases (15%). Twelve patients (60%) received cardiopulmonary resuscitation during prehospital care. NTVT affected the limbs (14 cases, 70%) and the abdomen or the small pelvis (6 cases, 30%). All the patients were operated in emergency. Arterial lesions were treated with greater saphenous vein bypasses, by ligation, and/or embolization. Eleven venous lesions were treated by direct repair or ligation. Associated lesions requiring a specific treatment were present in 19 patients (95%) and were primarily osseous, nervous, and abdomino-pelvic. Severe postoperative complications were observed in 9 patients (45%). Fourteen patients (70%) required blood transfusion (6.4 U of packed red blood cells on average, range 0-48). There were no deaths or amputation and all vascular reconstructions were patent at 6 months. CONCLUSIONS: The effectiveness of the prehospital emergency services and a multisite and multidisciplinary management made it possible to obtain satisfactory results for NTVT casualties. All the departments of vascular surgery must be prepared to receive many wounded victims in the event of terrorist attacks.

Inhibition of microRNA-92a prevents endothelial dysfunction and atherosclerosis in mice.

RATIONALE FOR STUDY: MicroRNAs (miRNAs) are small noncoding RNAs that regulate protein expression at post-transcriptional level. We hypothesized that a specific pool of endothelial miRNAs could be selectively regulated by flow conditions and inflammatory signals, and as such be involved in the development of atherosclerosis. OBJECTIVE: To identify miRNAs, called atheromiRs, which are selectively regulated by shear stress and oxidized low-density lipoproteins (oxLDL), and to determine their role in atherogenesis. METHODS AND RESULTS: Large-scale miRNA profiling in HUVECs identified miR-92a as an atheromiR candidate, whose expression is preferentially upregulated by the combination of low shear stress (SS) and atherogenic oxLDL. Ex vivo analysis of atheroprone and atheroprotected areas of mouse arteries and human atherosclerotic plaques demonstrated the preferential expression of miR-92a in atheroprone low SS regions. In Ldlr(-/-) mice, miR-92a expression was markedly enhanced by hypercholesterolemia, in particular in atheroprone areas of the aorta. Assessment of endothelial inflammation in gain- and loss-of-function experiments targeting miR-92a expression revealed that miR-92a regulated endothelial cell activation by oxLDL, more specifically under low SS conditions, which was associated with modulation of Kruppel-like factor 2 (KLF2), Kruppel-like factor 4 (KLF4), and suppressor of cytokine signaling 5. miR-92a expression was regulated by signal transducer and activator of transcription 3 in SS- and oxLDL-dependent manner. Furthermore, specific in vivo blockade of miR-92a expression in Ldlr(-/-) mice reduced endothelial inflammation and altered the development of atherosclerosis, decreasing plaque size and promoting a more stable lesion phenotype. CONCLUSIONS: Upregulation of miR-92a by oxLDL in atheroprone areas promotes endothelial activation and the development of atherosclerotic lesions. Therefore, miR-92a antagomir seems as a new atheroprotective therapeutic strategy.

Experience of the Zenith Dissection Endovascular System in the emergency setting of malperfusion in acute type B dissections.

OBJECTIVE: This study evaluated the safety and effectiveness of the Zenith Dissection Endovascular System (Cook Medical, Bloomington, Ind) in the urgent treatment of acute type B aortic dissections complicated by organ malperfusion. METHODS: Between June 2011 and June 2013, we prospectively enrolled all patients with acute type B dissection (<14 days) complicated by visceral malperfusion and treated by the Zenith Dissection Endovascular System, including a proximal covered stent and a distal noncovered stent. Organ malperfusion was diagnosed during the clinical, biological, and morphologic follow-up of patients admitted to a dedicated intensive care unit (SOS Aorta). End points were 30-day mortality and morbidity, and reoperation rate, survival, and remodelling of the dissected aorta during follow-up. RESULTS: Fifteen patients (11 men; mean age, 60 ± 12 years) were treated in emergency procedures with a median delay of 36 hours. Malperfusions included renal ischemia in all patients, intestinal ischemia in nine, and lower limb ischemia in six. The proximal entry tear in each patient was covered by a stent Zenith TX2 graft (mean diameter, 36 mm; mean length, 170 mm; Cook Medical), supplemented by a noncovered aortic stent (diameter, 36 or 46 mm; length, 164 mm) with a technical success rate of 100%. The left subclavian artery in 10 patients was covered without revascularization. One chimney was necessary to revascularize the left common carotid artery. Six patients required complementary arterial branch stenting for persistent static malperfusion, using eight peripheral stents (five iliacs, three renals). No deaths were recorded during the 30-day postoperative period. Major adverse events were reported in three patients (20%): 1 paraparesis with complete recovery, 1 colonic resection, 1 stroke, and 2 transient renal failures. The mean hospital stay was 14 ± 6 days. During a mean follow-up of 8 ± 3 months, one sudden death, no aortic-related complications, and no reoperations or conversions were recorded. Remodelling with healing of the thoracic false lumen was obtained in 10 patients (67%), and five others had a partially thrombosed false lumen without remodelling. CONCLUSIONS: Used as a treatment for organ malperfusion complicating acute type B dissections, the Zenith Dissection Endovascular System achieved safely and effectively satisfactory clinical results in the short term. The long-term effect of this composite treatment on aortic remodelling remains to be determined.