Jens Eldrup-Jorgensen

The Vascular Study Group of New England Cardiac Risk Index (VSG-CRI) predicts cardiac complications more accurately than the Revised Cardiac Risk Index in vascular surgery patients

OBJECTIVE The Revised Cardiac Risk Index (RCRI) is a widely used model for predicting cardiac events after noncardiac surgery. We compared the accuracy of the RCRI with a new, vascular surgery-specific model developed from patients within the Vascular Study Group of New England (VSGNE). METHODS We studied 10,081 patients who underwent nonemergent carotid endarterectomy (CEA; n = 5293), lower extremity bypass (LEB; n = 2673), endovascular abdominal aortic aneurysm repair (EVAR; n = 1005), and open infrarenal abdominal aortic aneurysm repair (OAAA; n = 1,110) within the VSGNE from 2003 to 2008. First, we analyzed the ability of the RCRI to predict in-hospital major adverse cardiac events, including myocardial infarction (MI), arrhythmia, or congestive heart failure (CHF) in the VSGNE cohort. Second, we used a derivation cohort of 8208 to develop a new cardiac risk prediction model specifically for vascular surgery patients. Chi-square analysis identified univariate predictors, and multivariate logistic regression was used to develop an aggregate and four procedure-specific risk prediction models for cardiac complications. Calibration and model discrimination were assessed using Pearson correlation coefficient and receiver operating characteristic (ROC) curves. The ability of the model to predict cardiac complications was assessed within a validation cohort of 1873. Significant predictors were converted to an integer score to create a practical cardiac risk prediction formula. RESULTS The overall incidence of major cardiac events in the VSGNE cohort was 6.3% (2.5% MI, 3.9% arrhythmia, 1.8% CHF). The RCRI predicted risk after CEA reasonably well but substantially underestimated risk after LEB, EVAR, and OAAA for low- and higher-risk patients. Across all VSGNE patients, the RCRI underestimated cardiac complications by 1.7- to 7.4-fold based on actual event rates of 2.6%, 6.7%, 11.6%, and 18.4% for patients with 0, 1, 2, and >or=3 risk factors. In multivariate analysis of the VSGNE cohort, independent predictors of adverse cardiac events were (odds ratio [OR]) increasing age (1.7-2.8), smoking (1.3), insulin-dependent diabetes (1.4), coronary artery disease (1.4), CHF (1.9), abnormal cardiac stress test (1.2), long-term beta-blocker therapy (1.4), chronic obstructive pulmonary disease (1.6), and creatinine >or=1.8 mg/dL (1.7). Prior cardiac revascularization was protective (OR, 0.8). Our aggregate model was well calibrated (r = 0.99, P < .001), demonstrating moderate discriminative ability (ROC curve = 0.71), which differed only slightly from the procedure-specific models (ROC curves: CEA, 0.74; LEB, 0.72; EVAR, 0.74; OAAA, 0.68). Rates of cardiac complications for patients with 0 to 3, 4, 5, and >or=6 VSG risk factors were 3.1%, 5.0%, 6.8%, and 11.6% in the derivation cohort and 3.8%, 5.2%, 8.1%, and 10.1% in the validation cohort. The VSGNE cardiac risk model more accurately predicted the actual risk of cardiac complications across the four procedures for low- and higher-risk patients than the RCRI. When the VSG Cardiac Risk Index (VSG-CRI) was used to score patients, six categories of risk ranging from 2.6% to 14.3% (score of 0-3 to 8) were discernible. CONCLUSIONS The RCRI substantially underestimates in-hospital cardiac events in patients undergoing elective or urgent vascular surgery, especially after LEB, EVAR, and OAAA. The VSG-CRI more accurately predicts in-hospital cardiac events after vascular surgery and represents an important tool for clinical decision making.

Vascular Endothelial Growth Factor Increases the Mitogenic Response to Fibroblast Growth Factor-2 in Vascular Smooth Muscle Cells In Vivo via Expression of fms-Like Tyrosine Kinase-1

Vascular endothelial growth factor (VEGF) has traditionally been considered an endothelial cell-specific factor inducing angiogenesis and vascular permeability in vivo. In the present study, expression of VEGF and its receptors, fetal liver kinase-1 (flk-1) and fms-like tyrosine kinase-1 (flt-1), was examined in rat carotid arteries after balloon injury. Although VEGF and flk-1 were not detectable, high levels of flt-1 mRNA and protein were expressed by smooth muscle cells (SMCs) in the neointima, as demonstrated by en face in situ hybridization and Western blotting. Intimal SMC proliferation in chronically denuded rat carotid arteries was unaffected by intraluminal infusion of VEGF, whereas fibroblast growth factor (FGF)-2 increased the number of replicating SMCs 4-fold. Pretreatment with VEGF doubled the mitogenic response to infused FGF-2 by increasing SMC replication in deeper layers of the intima. VEGF increased the permeability of chronically denuded vessels to plasma proteins but had no effect on the uptake of locally infused biotinylated FGF-2. These findings demonstrate that vascular SMCs express functional flt-1 receptors after arterial injury and that VEGF has synergistic effects with FGF-2 on SMC proliferation. These effects are likely to be mediated by a VEGF-mediated increase in permeability as well as a direct interaction between the VEGF and FGF signaling pathways.

A prospective, randomized trial of Unna's boots versus hydroactive dressing in the treatment of venous statis ulcers

In many centers the standard treatment for venous stasis ulcers consists of UB dressings. A new dressing, DuoDERM hydroactive dressing (HD), has recently been used extensively for the treatment of venous stasis ulcers. Because of this trend, a prospective, randomized trial of these two dressings was undertaken. Sixty-nine ulcers (39 HD and 30 UB) were randomized. End points were complete healing and development of complications necessitating cessation of treatment. Time to healing, cost of treatment, and patient convenience were also evaluated. Twenty-one of 30 ulcers (70%) healed with UB therapy compared with 15 of 39 ulcers (38%) treated with HD (p less than 0.01, CST). Life-table healing rates at 15 weeks were 64% for UB compared with 35% for HD (p = 0.01, log rank test). Ten of 39 patients (26%) receiving HD had complications compared with no complications in the UB group (p = 0.004, FET). For those patients whose ulcers healed, there was no significant difference (p = 0.51, STT) in the mean time required for healing or the average weekly cost of dressing materials between the HD group (7.0 weeks at +11.50 per week) and the UB group (8.4 weeks at +12.60 per week). Those patients treated with HD reported a significantly greater level of convenience than those patients with UB (p = 0.004, STT). Although treatment with HD led to better patient acceptance, those patients receiving UB therapy had a significantly greater rate of healing and a significantly lesser incidence of complications than those patients treated with HD.

Hypercoagulable states and lower limb ischemia in young adults

This study prospectively evaluates hypercoagulable states in patients under 51 years of age undergoing lower extremity revascularization for ischemia and assesses early outcome after operation. Twenty patients whose ages range from 23 to 50 years (mean 40.8 years) were identified prospectively who underwent lower extremity revascularization and evaluation of hypercoagulability. Fifteen patients were male (75%), 10 were black (50%), six had hypertension (30%), and four were diabetic (20%). All but two were cigarette smokers (90%). Seven aortoiliac procedures and 13 infrainguinal procedures were performed. Six patients had one or more abnormalities of regulatory proteins (protein S deficiency, four; protein C deficiency, three; presence of lupus-like anticoagulant, three; plasminogen deficiency, two). Eight of 17 patients in whom platelet aggregation profiles were obtained showed increased reactivity (47%). Only 4 of 17 patients (24%) were normal when tested for all parameters. Arterial or graft thrombosis developed in four of the 20 patients within 30 days after operation. Hypercoagulability was found in all four patients whose revascularizations failed. A high incidence of hypercoagulable states was found in patients under 51 years of age with lower limb ischemia requiring revascularization. Hypercoagulability may have contributed to early postoperative thrombosis of the vascular procedure.

Predicting 1-year mortality after elective abdominal aortic aneurysm repair.

OBJECTIVE Benefit of prophylactic abdominal aortic aneurysm (AAA) repair requires sufficient survival to overcome operative risk. Since death within 1 year of elective open or endovascular (EVAR) infrarenal AAA repair likely indicates ineffective treatment, we developed a prediction model for 1-year mortality to aid clinical decision-making. METHODS We used a prospective registry of 1387 consecutive patients who had undergone elective AAA repair from 2003 to 2007 by 50 surgeons from 11 hospitals in Northern New England. Cox proportional hazards were used to analyze potential risk factors for 1-year mortality, including medical comorbidities, aortic clamp site, preoperative risk factor modification (eg, beta-blockade), and aneurysm diameter. RESULTS Thirty-day and 1-year mortality after open repair (n = 748) was 2.3% and 5.8%, and after EVAR (n = 639) was 0.5% and 5.7%, respectively. Factors associated with death within 1-year after open repair were: age >/= 70 (P = .007; hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.3-6.3), history of chronic obstructive pulmonary disease (COPD) (P < .0001; HR 3.6, 95% CI 1.9-7.0), chronic renal insufficiency (creatinine >/= 1.8) (P = .008; HR 2.8, 95% CI 1.3-6.2) and suprarenal aortic clamp site (P < .0001; HR 3.8, 95% CI 1.9-7.5). Depending on the number of risk factors present, predicted 1-year mortality after open repair varied from 1% in patients with no risk factors to 67% in patients with four risk factors. Our model demonstrated excellent correlation between observed and expected deaths (r = 0.97). For EVAR, identified risk factors for death within 1 year included a history of congestive heart failure (CHF) (P = .002; HR 3.2, 95% CI 1.6-6.5), and aneurysm diameter >/=6.5 cm (P = .04 95% CI 1.0-4.8). Depending on the number of risk factors present, predicted mortality ranged from 3.6% to 23%. A model using CHF and aneurysm diameter correlated well with actual mortality rates, with an observed to expected ratio of 0.96. CONCLUSION Predictors of 1-year mortality can identify patients less likely to benefit from elective AAA repair. These factors differ for open repair vs EVAR and should be considered in individual patient decision-making. Our EVAR model had less impact on 1-year survival, even if CHF and large AAA diameter were present. However, a combination of age, COPD, renal insufficiency, and need for suprarenal clamping have significant impact on 1-year mortality after open AAA repair. Consideration of these variables should assist decision-making for elective AAA repair, especially in borderline cases.

Changing patterns in surgery for chronic renal artery occlusive diseases

We report 66 patients undergoing 69 operations for chronic renal artery occlusive diseases operated on at two institutions between January 1985 and June 1990. Etiology was atherosclerosis in 59 patients (90%); fibromuscular disease in four (6%), and three children with nonfibromuscular disease stenosis (4%). Atherosclerosis was local in 10 and generalized in 49 (83% of all patients). Fifty operations (72%) were for salvage of renal function. Average serum creatinine was 2.3 mg/dl and was elevated in 46 patients (70%). Donor arteries for reconstruction were aorta 20 (29%), aortic graft 16 (23%), and other abdominal arteries 33 (48%). Twenty-one patients had concomitant vascular procedures including 16 aortic replacements. The two operative deaths (3%) followed aortic replacements. Three grafts (4%) occluded before discharge from the hospital. Eighty-six percent of patients undergoing renal salvage avoided long-term dialysis. In past decades fibromuscular disease and localized atherosclerosis were the most frequent renal artery occlusive diseases undergoing surgery, hypertension was the predominant indication, and the most frequent operation was aortorenal bypass. As a result of improved pharmacologic management of hypertension and the development of percutaneous transluminal dilation, most patients in this series had far advanced generalized atherosclerosis, and renal salvage was the most frequent indication for operation. As a consequence of the severity of the atherosclerosis, 48% of operations avoided the aorta, 23% replaced the aorta, and aortorenal bypass was used in only 29%.

The early fate of venous repair after civilian vascular trauma. A clinical, hemodynamic, and venographic assessment.

Repair of major venous injuries of the extremities has been advocated to improve limb salvage rates and to prevent the early and late sequelae of venous interruption. The contribution of venous repair to the surgical outcome remains controversial, however, in part because the fate of venous reconstruction has previously not been well defined. The current study was done to determine the early patency rate of venous repair, to compare the accuracy of various methods used to assess venous patency, and to analyze the relationship between early venous patency and surgical outcome. During a recent 27-month period, 36 patients with major extremity venous injuries were treated by venous reconstruction; 34 patients (94%) had an associated major arterial injury that also required repair. Venous repair was performed in the upper extremity (22%) as well as the lower extremity (78%) using various reconstructive methods, including lateral repair (17%), end-to-end anastomosis (11%), autogenous vein patching (25%), interposition autogenous vein grafting (42%), and panelled autogenous vein grafting (6%). After operation, venous repair patency was evaluated by clinical examination, impedence plethysmography, and Doppler ultrasonography, and contrast venography. There were no perioperative deaths in these 36 patients. The limb salvage rate was 100% and all 34 major arterial repairs were patent at the time of hospital discharge. Venography performed on the seventh postoperative day demonstrated that 14 venous repairs had thrombosed (39%) and that 22 had remained patent (61%). Local venous repair had a significantly lower thrombosis rate (21%) than those requiring interposition vein grafting (59%) (p < 0.03). Compared with venography, the clinical evaluation was 67% accurate in the assessment of venous repair patency, and the noninvasive examination was 53% accurate. In conclusion, a substantial percentage of venous repairs will thrombose in the postoperative period, especially if interposition vein grafting is used. However, in this series limb salvage was not adversely influenced by an unexpectedly high rate of venous repair thrombosis. In addition, clinical evaluation and noninvasive testing did not provide an accurate assessment of venous patency after venous repair.

Factors associated with amputation or graft occlusion one year after lower extremity bypass in northern New England

BACKGROUND Optimal patient selection for lower extremity bypass surgery requires surgeons to predict which patients will have durable functional outcomes following revascularization. Therefore, we examined risk factors that predict amputation or graft occlusion within the first year following lower extremity bypass. METHODS Using our regional quality-improvement initiative in 11 hospitals in northern New England, we studied 2,306 lower extremity bypass procedures performed in 2,031 patients between January 2003 and December 2007. Sixty surgeons contributed to our database, and over 100 demographic and clinical variables were abstracted by trained researchers. Cox proportional hazards models were used to generate hazard ratios and surrounding 95% confidence intervals (CIs) for our combined outcome measure of major amputation (above-knee or below-knee) or permanent graft occlusion (loss of secondary patency) occurring within the first year postoperatively. RESULTS We found that within our cohort of 2,306 bypass procedures 17% resulted in an amputation or graft occlusion within 1 year of surgery. Of the 143 amputations performed (8% of all limbs undergoing bypasses), 17% occurred in the setting of a patent graft. Similarly, of the 277 graft occlusions (12% of all bypasses), 42% resulted in a major amputation. We identified eight preoperative patient characteristics associated with amputation or graft occlusion in multivariate analysis: age <50, nonambulatory status preoperatively, dialysis dependence, diabetes, critical limb ischemia, need for venovenostomy, tarsal target, and living preoperatively in a nursing home. While patients with no risk factors had 1-year amputation/occlusion rates that were <1%, patients with three or more risk factors had a nearly 30% chance of suffering amputation or graft occlusion by 1 year postoperatively. When we compared risk-adjusted rates of amputation/occlusion across centers, we found that one center in our region performed significantly better than expected (observed/expected ratio 0.7, 95% CI 0.6-0.9, p < 0.04). CONCLUSION Preoperative risk factors allow surgeons to predict the risk of amputation or graft occlusion following lower extremity bypass and to more precisely inform patients about their operative risk and functional outcomes. Additionally, our model facilitates comparison of risk-adjusted outcomes across our region. We believe quality-improvement measures such as these will allow surgeons to identify best practices and thereby improve outcomes across centers.

Factors associated with death 1 year after lower extremity bypass in Northern New England

BACKGROUND Using 30-day operative mortality reported with lower extremity bypass (LEB) in preoperative decision making may underestimate the actual death rate encountered before patients have truly recovered from surgery, especially in elderly, debilitated patients with significant tissue loss. Therefore, we examined preoperative, patient-level risk factors that predict survival within the first year following LEB. METHODS Using our regional quality improvement initiative in 11 hospitals in Northern New England, we studied 2306 LEB procedures performed in 2031 patients between January 2003 and December 2007. Sixty surgeons contributed to our database, and over 100 demographic and clinical variables were abstracted by trained researchers. Cox proportional hazards models were used to generate hazard ratios (HR) and surrounding 95% confidence intervals (CI) for our combined outcome measure of death occurring within the first year postoperatively. RESULTS We found that within our cohort of 2306 bypass procedures, 11% of patients died within 1 year of surgery (2% prior to discharge, 9% prior to 1-year follow-up). We identified six preoperative patient characteristics associated with higher risk of death in multivariate analysis: congestive heart failure (HR 1.3, 95% CI 1.0-1.8), diabetes (HR 1.5, 95% CI 1.1-2.1), critical limb ischemia (CLI) (HR 1.7, 95% CI 1.3-2.4), lack of single-segment saphenous vein (HR 1.9, 95% CI 1.5-2/5), age over 80 (HR 2.0, 95% CI 1.5-2.7), dialysis dependence (HR 2.7, 95% CI 1.9-3.6), and emergent nature of the procedure (HR 3.4, 95% CI 1.7-6.8). While patients with no risk factors had 1-year death rates that were less than 5%: patients with three or more risk factors had a 28% chance of dying before 1 year postoperatively. When we compared risk-adjusted survival across centers, we found that one center in our region performed significantly better than expected (observed-to-expected outcome ratio 0.7, 95% CI 0.6-0.9, P = .04). CONCLUSIONS Preoperative risk factors allow surgeons to predict survival in the first year following LEB, and to more precisely inform patients about their operative risk with LEB. Additionally, our model facilitates benchmarking comparison of risk-adjusted outcomes across our region. We believe quality improvement measures such as these will allow surgeons to identify best practices and thereby improve outcomes with LEB across centers.

Restenosis after carotid endarterectomy in a multicenter regional registry

BACKGROUND Level I evidence shows conventional carotid endarterectomy (CEA) with patch angioplasty results in lower rates of restenosis. However, whether this information has affected practice patterns and outcomes in real-world vascular surgery settings is unclear. METHODS Within the Vascular Study Group of New England (VSGNE), we studied 2981 patients undergoing 2981 first-time CEAs between January 1, 2003, and June 31, 2008. Rates of restenosis (defined by duplex ultrasound imaging at the 1-year follow-up) were estimated using life-table analysis. Cox proportional hazards models were used to identify multivariable predictors of postoperative restenosis ≤ 1 year. RESULTS Across 58 surgeons and 11 hospitals, we studied 2611 conventional CEAs (88% of all CEAs) and 370 eversion CEAs (12% of all CEAs). Median follow-up was 12.8 months (range, 1-35 months). The proportion of conventional CEAs performed with patching increased from 87% to 96% (P < .001) between 2003 and 2008, whereas eversion CEA declined from 18% to 5% (P < .001). Restenosis occurred in 303 patients (10%); by life-table analysis, the restenosis rate at 1 year was 6.2% (95% confidence interval [CI], 4.7%-6.8%). Restenoses were most commonly noncritical: 50%-79% restenosis in 7.9%, 80%-99% restenosis in 1.7%, and occlusion in 0.5%. Univariate analyses showed significant differences in 80% to 100% restenosis by procedure type (2% in conventional CEA, 6% in eversion CEA, P < .002), the year of procedure (3.2% in 2003, 0% in 2008; P < .03), and use of patching in conventional CEA (2.9% no patch, 1% with patch; P < .008). By multivariable analysis, absence of patching (hazard ratio [HR], 3.2; 95% CI, 1.5-7.0), contralateral internal carotid artery stenosis > 80% (HR, 4.1; 95% CI, 1.4-11.5), and dialysis dependence (HR, 3.5; 95% CI, 1.2-9.8) were independently associated with a higher risk of an 80% to 100% restenosis. Of the 51 patients with 80% to 99% restenosis, 14 underwent reintervention ≤ 1 year, comprising 4 reoperations and 10 carotid artery stent procedures. Of the 15 patients with a carotid occlusion ≤ 1 year, transient ischemic attacks occurred in 2 and a disabling stroke in 1. CONCLUSIONS In our region, restenosis after CEA, especially clinically significant restenosis ≤ 1 year after surgery, decreased slightly over time. This improvement in outcome was associated with several factors, including an increase in patching after conventional CEA, a process of care that was studied and encouraged within our vascular study group. These results highlight the utility of regional quality-improvement efforts in improving outcomes in vascular surgery.