Christopher T. Healey

Improving the Glasgow Coma Scale score: motor score alone is a better predictor

BACKGROUND The Glasgow Coma Scale (GCS) has served as an assessment tool in head trauma and as a measure of physiologic derangement in outcome models (e.g., TRISS and Acute Physiology and Chronic Health Evaluation), but it has not been rigorously examined as a predictor of outcome. METHODS Using a large trauma data set (National Trauma Data Bank, N = 204,181), we compared the predictive power (pseudo R2, receiver operating characteristic [ROC]) and calibration of the GCS to its components. RESULTS The GCS is actually a collection of 120 different combinations of its 3 predictors grouped into 12 different scores by simple addition (motor [m] + verbal [v] + eye [e] = GCS score). Problematically, different combinations summing to a single GCS score may actually have very different mortalities. For example, the GCS score of 4 can represent any of three mve combinations: 2/1/1 (survival = 0.52), 1/2/1 (survival = 0.73), or 1/1/2 (survival = 0.81). In addition, the relationship between GCS score and survival is not linear, and furthermore, a logistic model based on GCS score is poorly calibrated even after fractional polynomial transformation. The m component of the GCS, by contrast, is not only linearly related to survival, but preserves almost all the predictive power of the GCS (ROC(GCS) = 0.89, ROC(m) = 0.87; pseudo R2(GCS) = 0.42, pseudo R2(m) = 0.40) and has a better calibrated logistic model. CONCLUSION Because the motor component of the GCS contains virtually all the information of the GCS itself, can be measured in intubated patients, and is much better behaved statistically than the GCS, we believe that the motor component of the GCS should replace the GCS in outcome prediction models. Because the m component is nonlinear in the log odds of survival, however, it should be mathematically transformed before its inclusion in broader outcome prediction models.

Results of the Nellix system investigational device exemption pivotal trial for endovascular aneurysm sealing

OBJECTIVE The Nellix EndoVascular Aneurysm Sealing system (Endologix, Inc, Irvine, Calif) is a novel approach to abdominal aortic aneurysm (AAA) endovascular repair whereby biocompatible polymer is employed to exclude and to seal the AAA sac. We report 30-day results of the U.S. pivotal trial. METHODS Consecutive, eligible, consenting patients were enrolled at 29 sites in the United States and Europe. Inclusion criteria required an asymptomatic infrarenal AAA, with aortic neck length ≥10 mm and angle to the sac ≤60 degrees, aortic neck diameter of 18 to 32 mm, aneurysm blood lumen diameter ≤6 cm, common iliac artery lumen diameter of 9 to 35 mm, access artery diameter ≥6 mm, and serum creatinine level ≤2 mg/dL. Follow-up at 30 days included clinical assessment and computed tomography angiography evaluation of endoleaks and device integrity as assessed by a core laboratory. The primary safety end point is the incidence of independently adjudicated 30-day major adverse events (MAEs), with success defined as superiority with reference to the Society for Vascular Surgery open repair control group (56%). RESULTS Between January and November 2014, 150 trial patients having a mean AAA diameter of 5.8 cm were enrolled and treated with the Nellix system with 100% procedural success. One early death (0.7%) occurred secondary to multisystem organ failure. All 149 surviving patients completed 30-day follow-up. There were no aneurysm ruptures, conversions, limb thromboses, stent fractures, or stent kinking. Five early MAEs occurred in four patients (2.7%) and included one death, bowel ischemia (1), renal failure (2), and respiratory failure (1). One (0.7%) secondary intervention to treat inadvertent coverage of a renal artery was performed. The core laboratory identified nine (6%) endoleaks (one type I, eight type II) on 30-day computed tomography angiography. Freedom from MAE was 97.3% (95% confidence interval, 93.3%-99.0%). CONCLUSIONS In selected patients, perioperative outcomes with the Nellix system for endovascular aneurysm sealing are encouraging, with very low 30-day morbidity and mortality and high procedural success. The primary safety end point has been achieved. Longer term follow-up is in progress.

One-year pivotal trial outcomes of the Nellix system for endovascular aneurysm sealing

Objective: The Nellix EndoVascular Aneurysm Sealing (EVAS) System (Endologix, Inc, Irvine, Calif) is a novel approach to abdominal aortic aneurysm (AAA) treatment whereby polymer is used to fill the AAA sac. We report 1‐year results of the investigational device exemption pivotal trial. Methods: Eligible patients were treated at 30 sites in the United States and Europe. Inclusion criteria required an asymptomatic infrarenal AAA, with a neck length ≥10 mm and ≤60° angle, iliac artery blood lumen diameter 9 to 35 mm, access artery diameter ≥6 mm, and serum creatinine ≤2 mg/dL. Follow‐up included computed tomography angiography scans at 30 days, 6 months, and 1 year that were evaluated by a core laboratory. The primary safety end point was 30‐day major adverse events (MAEs), which were compared with a performance goal of <56% (the Society for Vascular Surgery open repair control group rate). The primary effectiveness end point was treatment success at 1 year, which was compared with a performance goal of >80%. Treatment success required procedural technical success and absence of AAA rupture during follow‐up, conversion to open surgical repair, endoleak (type I or III) at 1 year, migration >10 mm causing complications or requiring secondary intervention, aneurysm enlargement, or secondary procedures through 1 year for resolution of endoleak, device obstruction or occlusion, or device defect. Results: Of 150 treated patients, 149 (99.3%) completed 1‐year follow‐up. The MAEs rate at 30 days was 2.7% (95% confidence interval, 0.7%‐6.7%), satisfying the primary safety end point (<56%). The 1‐year treatment success was 94% (95% confidence interval, 88.6%‐97.4%), achieving the primary effectiveness end point (>80%). At 1 year, key secondary outcomes included 6.7% MAEs, 4.7% serious device‐related events, 1.3% AAA‐related mortality, 3.7% secondary interventions, and 0.7% surgical conversions. MAEs through 1 year included death (n = 6), stroke (n = 3), bowel ischemia (n = 2), renal failure (n = 2), respiratory failure (n = 2), and myocardial infarction (n =1). One iatrogenic AAA rupture occurred and one AAA rupture was reported during follow‐up. AAA sac enlargement (>5 mm) was 1.5% at 1 year. Endoleaks were present in four patients (3.1%) at 1 year (1 type Ib and 3 type II). Migration >10 mm occurred in three patients (2.3%), but none required secondary intervention. Conclusions: Outcomes with this novel endovascular therapy for AAA, the Nellix EVAS System, are encouraging. The primary safety and effectiveness end points have been met. Low morbidity, low mortality, and high procedural and treatment success were achieved despite the inevitability of a learning curve and unique risks associated with a new device and technique. Long‐term follow‐up is in progress.

Effect of chronic oral anticoagulation with warfarin on the durability and outcomes of endovascular aortic aneurysm repair.

OBJECTIVE Endoleak after endovascular aortic aneurysm repair (EVAR) can affect the durability of the repair and lead to continued sac expansion, rupture, and the need for further endovascular or open surgical interventions. The purpose of this study was to determine whether chronic anticoagulation therapy with warfarin is associated with an increased incidence of endoleak and thus increased need for reintervention after EVAR. METHODS We reviewed the records of 401 consecutive patients who underwent EVAR at a single institution from 2003 until 2011. Patients on warfarin were compared with a control group not on warfarin. Primary endpoints included reintervention, defined as rupture, explant, or angiography; death from any cause; and a composite outcome of reintervention or death. The presence of an endoleak at last follow-up, identified by computed tomography or ultrasound scan, and increase of more than 5 mm in aneurysm sac size were secondary endpoints. Cox proportional hazards models were used to estimate the effect of warfarin use on the primary and secondary outcomes, controlling for age, gender, obesity, specific comorbidities, antiplatelet drugs, statin use, and urgency of EVAR. RESULTS Three hundred sixty-three patients with a median follow-up period of 29 months had sufficient data for analysis. Warfarin use was not associated with an increased risk of any of the primary endpoints. Controlling for covariates and length of observation via proportional hazards models, the effect of warfarin remained insignificant. It was found, however, on regression analysis, that adverse outcomes were more prevalent after emergency EVAR and in patients deemed unfit for open surgical repair. CONCLUSIONS Chronic oral anticoagulation does not appear to affect the incidence of endoleak after EVAR, nor does it impact the need for reintervention or degree of sac regression. We feel that warfarin may be safely used in post-EVAR patients. It appears that adverse long-term outcomes are more likely after emergency EVAR and in patients deemed unfit for open surgery.

Refinement of anatomic indications for the Nellix System for endovascular aneurysm sealing based on 2-year outcomes from the EVAS FORWARD IDE trial

Background The Nellix System (Endologix, Inc, Irvine, Calif) for endovascular aneurysm sealing (EVAS) is a novel approach to abdominal aortic aneurysm treatment and conceptually different from endovascular aneurysm repair, whereby polymer is employed to fill and actively manage the abdominal aortic aneurysm sac. One‐year safety and effectiveness results of the Nellix pivotal trial demonstrated encouraging outcomes with very low morbidity and mortality and high procedural and treatment success. Two‐year imaging revealed a signal of migration, leading to a field safety notification issued by the manufacturer on October 21, 2016, and a dedicated root cause analysis, resulting in refinements to the instructions for use (IFU). We report the 2‐year results of the investigational device exemption pivotal trial stratified according to the new and original criteria for selection of patients. Methods Comprehensive engineering evaluations, statistical analyses, and clinical assessments were conducted looking at patients enrolled in the pivotal trial (N = 150), roll‐in cohort (N = 29), and continued access program (N = 154). All patients in all cohorts were treated on‐IFU at the time of enrollment. Logistic regression models supported the mechanism that migration with Nellix is associated with a small aortic flow lumen relative to a large aneurysm thrombus burden and large aortic neck diameters. Based on these findings, refinements to the IFU criteria were applied, excluding patients with a thrombus index (maximum aneurysm sac/maximum flow lumen diameter) >1.4, aortic neck diameter >28 mm, and aortic neck conicity (>10% diameter change along the infrarenal neck) and requiring a 10‐mm distal seal zone in the iliac artery. Results Freedom from all‐cause mortality at 2 years was 94%. Patient outcomes were then stratified on the refined morphologic criteria and analyzed retrospectively. Two‐year freedom from composite endoleak was high among both cohorts (95% on‐IFU vs 92% off‐IFU). Freedom from migration was 97.7% on‐IFU vs 93.2% off‐IFU (P = .0125). Freedom from aneurysm enlargement was 98.1% on‐IFU vs 93.5% off‐IFU (P value is not available because of failure of log‐rank test assumptions). Composite freedom from migration, type IA endoleak, or aneurysm expansion was 95.9% among the on‐IFU cohort vs 85.1% in the off‐IFU cohort (P = .0017). Conclusions Consistent with the introduction of a novel therapy, the presentation of failure modes of EVAS over time was inevitable. Using detailed imaging as well as engineering and statistical analysis, we were able to understand risk factors for adverse events specific to EVAS and defined those patients best suited for Nellix. With this EVAS‐specific approach to defining IFU, on‐IFU patients were identified as those with large aneurysms with little thrombus that would be prone to type II endoleaks and sac expansion with traditional devices. When treated with Nellix, these patients were predicted to experience exceptional results, especially with regard to a low composite endoleak rate and low all‐cause mortality.

PC020. Incidence and Clinical Outcomes of Small Abdominal Aortic Aneurysm Repair in the Vascular Quality Initiative

Objectives: Patients 80 years or older have significantly lower early mortality with endovascular aortic aneurysm repair (EVAR) when compared with open repair for abdominal aortic aneurysms (AAA). The long-term results in this older patient population remain poorly studied. We analyzed the results of emergent and elective AAA repair in patients 80 years or older who had at least 5 years of follow-up. Methods: A retrospective review of a prospectively collected vascular surgery database at a university-affiliated medical center was performed to identify all patients who underwent repair of an AAA between 2007 and 2012 and were 80 years of age or older at the time of surgery. Open and EVAR groups were compared for outcomes using univariate statistics. Results: The study cohort comprised 314 patients (mean age, 83.5 6 2.9 years) who underwent repair (96 open repair, 218 EVAR). Patients treated with open repair and EVAR had similar comorbidities, except that EVAR patients were more likely to bemale, and open repair patients were more likely to have larger aneurysms. When compared with open repair, elective early postoperative mortality was significantly lower for EVAR patients (1% vs 14%; P < .001). Overall mean life expectancy was 5.9 years (5.8 years EVAR, 5.8 years open repair; P 1⁄4 .98). The 1-year survival was significantly higher for EVAR (92.9%) compared with open repair (84.1%; P 1⁄4 .02). Although 2-year survivals (83.4% EVAR, 74.6% open repair; P 1⁄4 .07), and 5-year survivals (57.8% EVAR, 60.3% open repair; P 1⁄4 .98)

Behavioral Risk Factors and Regional Variation in Cardiovascular Health Care and Death

INTRODUCTION Reducing the burden of death from cardiovascular disease includes risk factor reduction and medical interventions. METHODS This was an observational analysis at the hospital service area (HSA) level, to examine regional variation and relationships between behavioral risks, health services utilization, and cardiovascular disease mortality (the outcome of interest). HSA-level prevalence of cardiovascular disease behavioral risks (smoking, poor diet, physical inactivity) were calculated from the Behavioral Risk Factor Surveillance System; HSA-level rates of stress tests, diagnostic cardiac catheterization, and revascularization from a statewide multi-payer claims data set from Maine in 2013 (with 606,260 patients aged ≥35 years), and deaths from state death certificate data. Analyses were done in 2016. RESULTS There were marked differences across 32 Maine HSAs in behavioral risks: smoking (12.4%-28.6%); poor diet (43.6%-73.0%); and physical inactivity (16.4%-37.9%). After adjustment for behavioral risks, rates of utilization varied by HSA: stress tests (28.2-62.4 per 1,000 person-years, coefficient of variation=17.5); diagnostic cardiac catheterization (10.0-19.8 per 1,000 person-years, coefficient of variation=17.3); and revascularization (4.6-6.2 per 1,000 person-years; coefficient of variation=9.1). Strong HSA-level associations between behavioral risk factors and cardiovascular disease mortality were observed: smoking (R2=0.52); poor diet (R2=0.38); and physical inactivity (R2=0.35), and no association between revascularization and cardiovascular disease mortality after adjustment for behavioral risk factors (R2=0.02). HSA-level behavioral risk factors were also strongly associated with all-cause mortality: smoking (R2=0.57); poor diet (R2=0.49); and physical inactivity (R2=0.46). CONCLUSIONS There is substantial regional variation in behavioral risks and cardiac utilization. Behavioral risk factors are associated with cardiovascular disease mortality regionally, whereas revascularization is not. Efforts to reduce cardiovascular disease mortality in populations should focus on prevention efforts targeting modifiable risk factors.