April 2021

Synopsis: Anemia in the context of acute myocardial infarction (AMI) is associated with increased cardiovascular mortality. However, it is not well studied at what threshold transfusion would be indicated so as to affect this risk. Thus, the goal of this study was to compare restrictive versus liberal transfusion requirements as it relates to major adverse cardiovascular outcomes up to 30 days after AMI.

This study was a unblinded, randomized control trial comparing liberal (transfusion for hemoglobin under 10 g/dL) to restrictive (transfusion for hemoglobin under 8 g/dL). The main outcome was measuring major acute cardiovascular events (MACE) at 30 days, which included all-cause death, recurrent myocardial infarction, emergency revascularization prompted by ischemia, and stroke. The analysis was separated into as-randomized and as-treated, which is used in non-inferiority studies instead of intention to treat analysis. 668 subjects were enrolled in 35 different centers across France and Spain from March 2016 – September 2019. Inclusion criteria was those older than 18 years of age with AMI (both STEMI or NSTEMI with elevated biomarkers) in the last 48 hours and hemoglobin between 7 and 10 g/dL during admission. Exclusion criteria included those in shock, AMI after CABG or PCI, life threatening bleeding, blood transfusion in the last 30 days, and malignant hematologic disease. Of the 668 subjects, 324 were randomized to the liberal transfusion group and 342 to the restrictive group. At day 30, in the as-treated population, MACE had occurred in 14% of those in the liberal group versus 11% of those in the restrictive group (relative risk 0.79, 1-sided 97.5% CI, 0.00-1.17) deeming the restrictive strategy non-inferior. Similar results were found in the as randomized population (relative risk 0.78, 1-sided 97.5%, 0.00-1.17). Due to high risk of type 1 error and inability to statical criteria because of sample size, secondary outcome were reported but not statistically analyzed; however, death occurred in 7.7% of the liberal group versus 5.6% of the restrictive, non-fatal recurrent MI occurred in 3.1% of the liberal group versus 2.1% in the restrictive, emergency revascularized occur in 1.9% in the liberal group versus 1.5% of the restrictive, and non-fatal ischemic stroke happened equally in both groups (0.6%). More people in the liberal group received greater than 1 unit of blood and patients in the liberal group were more likely to have acute lung injury and develop an infection. Overall, the authors conclude that in patients with AMI and anemia, a restrictive transfusion strategy was non-inferior compared to a liberal transfusion strategy in regards to 30 day MACE. 

Take home point: Restrictive transfusion strategy (lower transfusion threshold) in those who’ve had an acute myocardial infarction with anemia is safe and non-inferior to a more liberal transfusion strategy. A larger study is needed to compare superiority of one protocol to the other. 

Synopsis: As the population ages worldwide, patients 65 years and older have been found to undergo higher rates of surgery compared to other age groups. Unfortunately, this group is also more likely to die and suffer postoperative complications. Previous work found that frailty may be a better predictor of poor outcomes than age, but little is known regarding this association in emergency surgery or whether it varies by procedure risk.

This retrospective cross-sectional study evaluated Medicare administrative file claims between January 2007 through December 2015 to determine if there was an association between frailty and mortality among patients who had undergone one of seven designated emergency general surgery procedures that were stratified as low versus high risk. Cholecystectomy and appendectomy were considered low risk, while laparotomy, colectomy, lysis of adhesions, peptic ulcer repair, and small bowel resection were considered high risk. This stratification was based on earlier work from the same group.1 All patients were 65 years or older and individual frailty was determined via a claims-based frailty index. This index uses Medicare claims such as those for hospital admission, comorbid conditions, and medical equipment to assign a score from 0 to 1, with a score of >0.25 considered “frail.” 

Of the 882,929 emergency general surgery patients identified, 12.6% were considered frail (111,513 patients). While not unexpected, the authors found that frail patients were more likely to die within thirty days compared to non-frail patients (9.9% vs. 3.79%, P<0.001) and that frailty was independently associated with mortality even after controlling for patient and hospital characteristics. However, although overall mortality was greater in the high risk procedures, the association between frailty and mortality was actually stronger within low-risk procedures (appendectomy and cholecystectomy) compared to high risk procedures (adjusted odds ratio of 2.05 versus 1.53). Interestingly, this increased association was actually more pronounced in patients undergoing laparoscopic procedures as compared to open (odds ratios of 2.08 versus 1.38 in laparoscopic procedures compared to 1.91 versus 1.63 in open). 

The major finding is that frail patients were twice as likely to die within thirty days after cholecystectomy or appendectomy compared to non-frail patients and that this relative risk was greater than in more high risk procedures. This insinuates that essentially all emergency general surgery procedures should be considered high risk in older, frail patients, including laparoscopic appendectomy and cholecystectomy. This increased association between frailty in mortality among low-stress procedures has actually been seen in the elective orthopedic setting as well.2 These orthopedic authors highlight the need to optimize the patient beforehand, however, this is often not an option in emergency general surgery where the required intervention is often urgent or emergent in nature. At the very least, until there are better ways to optimize patients in the short term, great care must be taken to take frailty into consideration and have frank discussions with patients about the risks of any procedure in the emergent setting. Other calls to action include developing better ways to identify frail patients preoperatively and finding ways to better optimize postoperative recovery in those who do undergo operative intervention. 

1. Feeney T, Castillo-Angeles M, Scott JW, Nitzschke SL, Salim A, Haider AH, Havens JM. The independent effect of emergency general surgery on outcomes varies depending on case type: A NSQIP outcomes study. Am J Surg. 2018 Nov;216(5):856-862. doi: 10.1016/j.amjsurg.2018.03.006. Epub 2018 Mar 7. PMID: 29534818.
2. Shinall MC Jr, Arya S, Youk A, Varley P, Shah R, Massarweh NN, Shireman PK, Johanning JM, Brown AJ, Christie NA, Crist L, Curtin CM, Drolet BC, Dhupar R, Griffin J, Ibinson JW, Johnson JT, Kinney S, LaGrange C, Langerman A, Loyd GE, Mady LJ, Mott MP, Patri M, Siebler JC, Stimson CJ, Thorell WE, Vincent SA, Hall DE. Association of Preoperative Patient Frailty and Operative Stress With Postoperative Mortality. JAMA Surg. 2019 Nov 13;155(1):e194620. doi: 10.1001/jamasurg.2019.4620. Epub ahead of print. PMID: 31721994; PMCID: PMC6865246. 

Synopsis: With recent advances in endovascular technology, endovascular aneurysm repair (EVAR) has become the most commonly used intervention for abdominal aortic aneurysm (AAA) repair, accounting for more than 80% of AAA repairs in the United States. However, unfavorable anatomy of the infrarenal aortic neck or involvement of visceral vessels, which are present in up to 40% of patients with AAA’s, preclude patients from an endovascular treatment option; and open repair remains the standard treatment of choice in most centers.e

Most commercially available endovascular devices require an infrarenal proximal neck >15mm; therefore, modified endovascular techniques have been developed to overcome these anatomical constraints. EVAR with fenestrations/scallops, or openings in the graft fabric to accommodate visceral arteries, has been deployed to improve the proximal seal by incorporating the visceral vessels into the ‘seal zone’ in AAA’s with inadequate proximal neck. The ‘ZFen’ or Zenith Fenestrated AAA Endovascular Graft (William A. Cook Australia, Brisbane, Australia) is a commercially available, custom-made, endograft that was approved by the Food and Drug Administration in 2012 for the treatment of juxtarenal AAA’s with short necks (4-14 mm) using fenestrations/scallop for the renal arteries and/or SMA (see image).

“Final 5-year results of the United States Zenith Fenestrated prospective multicenter study for juxtarenal abdominal aortic aneurysms”, published in the Journal of Vascular Surgery in September 2020, reports the final 5-year results of the prospective multicenter trial designed to evaluate the Zfen. The trial enrolled 67 patients with juxtarenal AAA’s with proximal necks ranging 4-14 mm between 2005 and 2012 in 14 highly skilled U.S. academic medical centers in endovascular technology. The outcomes studied included major adverse events, renal stent stenosis/occlusion, changes in renal function, device migration, endoleaks, aneurysm sac enlargement, secondary interventions, and all-cause and aneurysm-related mortality. 

The mean follow-up was ~ 5 years. There were no ruptures or conversions to open repair. OF the 129 renal arteries targeted by fenestrations and stented, 14 developed in-stent restenosis and 5 occluded (18/19 of these had bare-metal stents) for which 13 underwent redo-angioplasty/stenting, 2 required bypass (occluded renal arteries), and a failed thrombectomy. One patient with pre-existing kidney dysfunction required dialysis. During the 5 years, there were 2 device migrations (>10 mm), 1 type 1A endoleak, 1 type 1B endoleak, and 24 type II endoelaks. There were 4 aneurysm sac enlargements (80% had sac shrinkage over 5 years). Twenty patients required secondary interventions (12 for renal stenosis/occlusion, 7 for endoleaks, 1 for both). There were 7 deaths (1 within 30 days secondary to bowel ischemia which was procedure related and 6 past 30 days where non-procedure related). Five-year freedom from all-cause mortality was 88.8% +/- 4.2% and five-year freedom from aneurysm-related mortality was 96.8% +/- 2.3%.

This study confirms the long-term safety and effectiveness of the Zfen device for the treatment of short-neck or juxtarenal AAAs. There was a low rate of type I endoleaks, device migration and sac enlargement. The most common reason for secondary interventions was renal stent stenosis and was mainly associated with the use of bare-metal stents, and that has been widely replaced by covered stents now. The Zfen is currently the only FDA approved device for the treatment of para-visceral AAAs, but there are multiple ongoing clinical trials investigating the endovascular treatment of more challenging AAA anatomies. It is important to note that these results are derived from procedures performed in high-volume excellence centers by highly experienced technical surgeons in a study with very strict inclusion criteria with regards to AAA anatomy and patient characteristics; and therefore real-practice might not be as promising.