Protocol for the Metformin Aneurysm Trial (MAT): a placebo-controlled randomised trial testing whether metformin reduces the risk of serious complications of abdominal aortic aneurysm.

BACKGROUND: Multiple observational studies have associated metformin prescription with reduced progression of abdominal aortic aneurysm (AAA). The Metformin Aneurysm Trial (MAT) will test whether metformin reduces the risk of AAA rupture-related mortality or requirement for AAA surgery (AAA events) in people with asymptomatic aneurysms. METHODS: MAT is an international, multi-centre, prospective, parallel-group, randomised, placebo-controlled trial. Participants must have an asymptomatic AAA measuring at least 35 mm in maximum diameter, no diabetes, no contraindication to metformin and no current plans for surgical repair. The double-blind period is preceded by a 6-week, single-blind, active run-in phase in which all potential participants receive metformin. Only patients tolerating metformin by taking at least 80% of allocated medication will enter the trial and be randomised to 1500 mg of metformin XR or an identical placebo. The primary outcome is the proportion of AAA events defined as rupture-related mortality or need for surgical repair. Secondary outcomes include AAA growth, major adverse cardiovascular events and health-related quality of life. In order to test if metformin reduced the risk of AAA events by at least 25%, 616 primary outcome events will be required (power 90%, alpha 0.05). DISCUSSION: Currently, there is no drug therapy for AAA. Past trials have found no convincing evidence of the benefit of multiple blood pressure lowering, antibiotics, a mast cell inhibitor, an anti-platelet drug and a lipid-lowering medication on AAA growth. MAT is one of a number of trials now ongoing testing metformin for AAA. MAT, unlike these other trials, is designed to test the effect of metformin on AAA events. The international collaboration needed for MAT will be challenging to achieve given the current COVID-19 pandemic. If this challenge can be overcome, MAT will represent a trial unique within the AAA field in its large size and design. TRIAL REGISTRATION: Australian Clinical Trials ACTRN12618001707257 . Registered on 16 October 2018.

Hybrid Management of an Aortobronchial Fistula after Patch Aortoplasty for Aortic Coarctation in a Patient with SARS-CoV-2 Pneumonia: Case Report and Review of the Literature.

Aortobronchial fistula is a rare cause of repeated hemoptysis and a potentially fatal condition if left untreated. We present the case of a 40-year-old man with repeated hemoptysis, excessive cough, and epistaxis ongoing for several days after SARS-CoV-2 pneumonia diagnosis. The patient had a history of patch aortoplasty for aortic coarctation and aortic valve replacement with a mechanical valve for aortic insufficiency due to bicuspid aortic valve at the age of 24. Computed tomography scan performed at presentation revealed a severely dilated ascending aorta, a thoracic aorta pseudoaneurysm at the site of the former coarctation, an aortobronchial fistula suggested by the thickened left lower lobe apical segmental bronchus in contact with the pseudoaneurysm and signs of alveolar hemorrhage in the respective segment. The patient was treated with thoracic endovascular aneurysm repair (TEVAR) after prior hemi-aortic arch debranching and transposition of the left common carotid artery and subclavian artery through a closed-chest surgical approach. Our case report together with a systematic review of the literature highlight the importance of both considering an aortobronchial fistula in the differential diagnosis of hemoptysis in patients with prior history of thoracic aorta surgical intervention, regardless of associated pathology, and of taking into account endovascular and hybrid techniques as an alternative to open surgical repair, which carries a high risk of morbidity and mortality.

Managing Emergent Surgery for Ruptured Abdominal Aortic Aneurysm during the COVID-19 Pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic which may compromise the management of vascular emergencies. An uncompromised treatment for ruptured abdominal aortic aneurysm (rAAA) during such a health crisis represents a challenge. This study aimed to demonstrate the treatment outcomes of rAAA and the perioperative prevention of cross-infection under the COVID-19 pandemic. METHODS: In cases of rAAA during the pandemic, a perioperative workflow was applied to expedite coronavirus testing and avoid pre-operative delay, combined with a strategy for preventing cross-infection. Data of rAAA treated in 11 vascular centers between January-March 2020 collected retrospectively were compared to the corresponding period in 2018 and 2019. RESULTS: Eight, 12, and 14 rAAA patients were treated in 11 centers in January-March 2018, 2019, and 2020, respectively. An increased portion were treated at local hospitals with a comparable outcome compared with large centers in Guangzhou. With EVAR-first strategy, 85.7% patients with rAAA in 2020 underwent endovascular repair, similar to that in 2018 and 2019. The surgical outcomes during the pandemic were not inferior to that in 2018 and 2019. The average length of ICU stay was 1.8 ± 3.4 days in 2020, tending to be shorter than that in 2018 and 2019, whereas the length of hospital stay was similar among 3 years. The in-hospital mortality of 2018, 2019, and 2020 was 37.5%, 25.0%, and 14.3%, respectively. Three patients undergoing emergent surgeries were suspected of COVID-19, though turned out to be negative after surgery. CONCLUSIONS: Our experience for emergency management of rAAA and infection prevention for healthcare providers is effective in optimizing emergent surgical outcomes during the COVID-19 pandemic.

Results of Transarterial Embolization for Treating Type 2 Endoleaks: A Single-Center Experience.

BACKGROUND: Type 2 endoleaks (T2Es) are the main cause of reintervention after endovascular repair of abdominal aortic aneurysms (EVAR). The objective of this study is to quantify success rates of T2E treatment. METHODS: This study involves a retrospective analysis of a prospectively maintained database containing data on all consecutive patients treated for a T2E between 2003 and 2017 in a single center. Technical success was defined as absence of endoleak in the final angiographic control after treatment. Clinical success was defined as absence of sac growth over 5 mm in the contrast-enhanced computed tomography performed a year thereafter. Statistics included Kaplan-Meier survival estimates. RESULTS: A total of 528 elective EVARs were performed in the period. Thirty-six of these (6.8%) developed a T2E requiring reintervention, a median of 37.9 months after EVAR. Twenty-five percent of the treatments were performed more than 5 years after intervention. Twenty-eight of the 36 treatments were performed via transarterial embolization. For this technique, technical success was 71.4% and clinical success was 62.5%. A subsequent reintervention was required in 35.7% of patients. In this cohort, the rate of aneurysm rupture was 10.7% (n = 3/28), open surgical conversion was needed in 2 of 28 cases (7.1%), and rate of aneurysm-related death was 14.3% (n = 4/28) over follow-up. CONCLUSIONS: A high percentage of patients are at risk of adverse outcomes after T2E treatment. Strict imaging follow-up is still needed in this population.

ACTION-1: study protocol for a randomised controlled trial on ACT-guided heparinization during open abdominal aortic aneurysm repair.

BACKGROUND: Heparin is used worldwide for 70 years during all non-cardiac arterial procedures (NCAP) to reduce thrombo-embolic complications (TEC). But heparin also increases blood loss causing possible harm for the patient. Heparin has an unpredictable effect in the individual patient. The activated clotting time (ACT) can measure the effect of heparin. Currently, this ACT is not measured during NCAP as the standard of care, contrary to during cardiac interventions, open and endovascular. A RCT will evaluate if ACT-guided heparinization results in less TEC than the current standard: a single bolus of 5000 IU of heparin and no measurements at all. A goal ACT of 200-220 s should be reached during ACT-guided heparinization and this should decrease (mortality caused by) TEC, while not increasing major bleeding complications. This RCT will be executed during open abdominal aortic aneurysm (AAA) surgery, as this is a standardized procedure throughout Europe. METHODS: Seven hundred fifty patients, who will undergo open AAA repair of an aneurysm originating below the superior mesenteric artery, will be randomised in 2 treatment arms: 5000 IU of heparin and no ACT measurements and no additional doses of heparin, or a protocol of 100 IU/kg bolus of heparin and ACT measurements after 5 min, and then every 30 min. The goal ACT is 200-220 s. If the ACT after 5 min is < 180 s, 60 IU/kg will be administered; if the ACT is between 180 and 200 s, 30 IU/kg. If the ACT is > 220 s, no extra heparin is given, and the ACT is measured after 30 min and then the same protocol is applied. The expected incidence for the combined endpoint of TEC and mortality is 19% for the 5000 IU group and 11% for the ACT-guided group. DISCUSSION: The ACTION-1 trial is an international RCT during open AAA surgery, designed to show superiority of ACT-guided heparinization compared to the current standard of a single bolus of 5000 IU of heparin. A significant reduction in TEC and mortality, without more major bleeding complications, must be proven with a relevant economic benefit. TRIAL REGISTRATION {2A}: NTR NL8421 ClinicalTrials.gov NCT04061798 . Registered on 20 August 2019 EudraCT 2018-003393-27 TRIAL REGISTRATION: DATA SET {2B}: Data category Information Primary registry and trial identifying number ClinicalTrials.gov : NCT04061798 Date of registration in primary registry 20-08-2019 Secondary identifying numbers NTR: NL8421 EudraCT: 2018-003393-27 Source(s) of monetary or material support ZonMw: The Netherlands Organisation for Health Research and Development Dijklander Ziekenhuis Amsterdam UMC Primary sponsor Dijklander Ziekenhuis Secondary sponsor(s) N/A Contact for public queries A.M. Wiersema, MD, PhD Arno@wiersema.nu 0031-229 208 206 Contact for scientific queries A.M. Wiersema, MD, PhD Arno@wiersema.nu 0031-229 208 206 Public title ACT Guided Heparinization During Open Abdominal Aortic Aneurysm Repair (ACTION-1) Scientific title ACTION-1: ACT Guided Heparinization During Open Abdominal Aortic Aneurysm Repair, a Randomised Trial Countries of recruitment The Netherlands. Soon the recruitment will start in Germany Health condition(s) or problem(s) studied Abdominal aortic aneurysm, arterial disease, surgery Intervention(s) ACT-guided heparinization 5000 IU of heparin Key inclusion and exclusion criteria Ages eligible for the study: ≥18 years Sexes eligible for the study: both Accepts healthy volunteers: no Inclusion criteria: Study type Interventional Allocation: randomized Intervention model: parallel assignment Masking: single blind (patient) Primary purpose: treatment Phase IV Date of first enrolment March 2020 Target sample size 750 Recruitment status Recruiting Primary outcome(s) The primary efficacy endpoint is 30-day mortality and in-hospital mortality during the same admission. The primary safety endpoint is the incidence of bleeding complications according to E-CABG classification, grade 1 and higher. Key secondary outcomes Serious complications as depicted in the Suggested Standards for Reports on Aneurysmal disease: all complications requiring re-operation, longer hospital stay, all complications.

Management of a Mycotic Aneurysm in a Patient with COVID-19: A Case Report.

The aim of this paper is to share our experience in managing a patient with Klebsiella pneumoniae mycotic abdominal aortic aneurysm who was also infected with COVID-19. A 69-year-old male was transferred to our hospital for the management of an infra-renal mycotic abdominal aortic aneurysm. During his hospital course, the patient contracted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). He was intubated due to respiratory distress. Over a short period, his mycotic aneurysm increased in size from 2.5 cm to 3.9 cm. An emergency repair of his expanding aneurysm was achieved using our previously described protocol of coating endovascular stents with rifampin. The patient was managed with a rifampin-coated endovascular stent graft without any major complications. Postoperatively, the patient did not demonstrate any neurological deficits nor any vascular compromise. He remained afebrile during his postoperative course and was extubated sometime thereafter. He was then transferred to the ward for additional monitoring prior to his discharge to a rehab hospital while being on long-term antibiotics. During his hospital stay, he was monitored with serial ultrasounds to ensure the absence of abscess formation, aortic aneurysm growth or graft endoleak. At 6 weeks after stent graft placement, he underwent a CT scan, which showed a patent stent graft, with a residual sac size of 2.5 cm without any evidence of abscess or endoleak. Over a follow-up period of 180 days, the patient remained asymptomatic while remaining on long-term antibiotics. Thus, in patients whose surgical risk is prohibitive, endovascular stent grafts can be used as a bridge to definitive surgical management.

Modelling the impact of changes to abdominal aortic aneurysm screening and treatment services in England during the COVID-19 pandemic.

BACKGROUND: The National Health Service (NHS) abdominal aortic aneurysm (AAA) screening programme (NAAASP) in England screens 65-year-old men. The programme monitors those with an aneurysm, and early intervention for large aneurysms reduces ruptures and AAA-related mortality. AAA screening services have been disrupted following COVID-19 but it is not known how this may impact AAA-related mortality, or where efforts should be focussed as services resume. METHODS: We repurposed a previously validated discrete event simulation model to investigate the impact of COVID-19-related service disruption on key outcomes. This model was used to explore the impact of delayed invitation and reduced attendance in men invited to screening. Additionally, we investigated the impact of temporarily suspending scans, increasing the threshold for elective surgery to 7cm and increasing drop-out in the AAA cohort under surveillance, using data from NAAASP to inform the population. FINDINGS: Delaying invitation to primary screening up to two years had little impact on key outcomes whereas a 10% reduction in attendance could lead to a 2% lifetime increase in AAA-related deaths. In surveillance patients, a 1-year suspension of surveillance or increase in the elective threshold resulted in a 0.4% increase in excess AAA-related deaths (8% in those 5-5.4cm at the start). Longer suspensions or a doubling of drop-out from surveillance would have a pronounced impact on outcomes. INTERPRETATION: Efforts should be directed towards encouraging men to attend AAA screening service appointments post-COVID-19. Those with AAAs on surveillance should be prioritised as the screening programme resumes, as changes to these services beyond one year are likely to have a larger impact on surgical burden and AAA-related mortality.

Aortoenteric fistula after endovascular mycotic aortic aneurysm exclusion: lessons learned during the COVID-19 era.

We report a case of aortoenteric fistula 2 years following endovascular aortic aneurysm repair (EVAR) for mycotic aneurysm presenting as upper gastrointestinal bleeding. Initial CT angiogram did not reveal the bleeding or connection to bowel, but endoscopy was suspicious of endograft in the duodenum. Management required a multidisciplinary approach. To stabilise the patient and to control bleeding, a 'bridging' endograft extension was performed. This was followed by open surgical removal of the EVAR endograft and lower limb in situ revascularisation. During postoperative recovery, the patient developed atypical, staged multisystemic symptoms (cardiac, pulmonary and neurological). With increasing awareness of the COVID-19 pandemic, the patient was found SARS-CoV-2-positive, which explained the progression of his symptoms. This was also reflected on other case reports in literature later.

Reassessing the operative threshold for abdominal aortic aneurysm repair in the context of COVID-19.

OBJECTIVE: The worldwide pandemic involving the novel respiratory syndrome (COVID-19) has forced health care systems to delay elective operations, including abdominal aortic aneurysm (AAA) repair, to conserve resources. This study provides a structured analysis of the decision to delay AAA repair and quantify the potential for harm. METHODS: A decision tree was constructed modeling immediate repair of AAA relative to an initial nonoperative (delayed repair) approach. Risks of COVID-19 contraction and mortality, aneurysm rupture, and operative mortality were considered. A deterministic sensitivity analysis for a range of patient ages (50 to >80), probability of COVID-19 infection (0.01%-30%), aneurysm size (5.5 to >7 cm), and time horizons (3-9 months) was performed. Probabilistic sensitivity analyses were conducted for three representative ages (60, 70, and 80). Analyses were conducted for endovascular aortic aneurysm repair (EVAR) and open surgical repair (OSR). RESULTS: Patients with aneurysms 7 cm or greater demonstrated a higher probability of survival when treated with immediate EVAR or OSR, compared with delayed repair, for patients under 80 years of age. When considering EVAR for aneurysms 5.5 to 6.9 cm, immediate repair had a higher probability of survival except in settings with a high probability of COVID-19 infection (10%-30%) and advanced age (70-85+ years). A nonoperative strategy maximized the probability of survival as patient age or operative risk increased. Probabilistic sensitivity analyses demonstrated that patients with large aneurysms (>7 cm) faced a 5.4% to 7.7% absolute increase in the probability of mortality with a delay of repair of 3 months. Young patients (60-70 years) with aneurysms 6 to 6.9 cm demonstrated an elevated risk of mortality (1.5%-1.9%) with a delay of 3 months. Those with aneurysms 5 to 5.9 cm demonstrated an increased survival with immediate repair in young patients (60); however, this was small in magnitude (0.2%-0.8%). The potential for harm increased as the length of surgical delay increased. For elderly patients requiring OSR, in the context of endemic COVID-19, delay of repair improves the probability of survival. CONCLUSIONS: The decision to delay operative repair of AAA should consider both patient age and local COVID-19 prevalence in addition to aneurysm size. EVAR should be considered when possible due to a reduced risk of harm and lower resource utilization.

Ruptured Abdominal Aortic Aneurysm Treated with Endovascular Repair in a Patient with Active COVID-19 Infection during the Pandemic.

We report a patient who presented with acute abdominal pain during the COVID-19 pandemic. His work-up revealed rupture of a 5.8 cm abdominal aortic aneurysm. He also had fever, cough, and shortness of breath and radiologic evidence of COVID-19 infection. After careful consideration, he underwent successful endovascular repair under local anesthesia with good short-term results.