Michael T. Watkins

Risk Stratification for Postoperative Cardiovascular Events via Noninvasive Assessment of Endothelial Function A Prospective Study

Background—Brachial artery endothelial function is impaired in individuals with atherosclerosis and coronary risk factors and improves with risk reduction therapy. However, the predictive value of brachial artery endothelial dysfunction for future cardiovascular events is unknown. Methods and Results—We preoperatively examined brachial artery vasodilation using ultrasound in 187 patients undergoing vascular surgery. Patients were prospectively followed for 30 days after surgery. Forty-five patients had a postoperative event, including cardiac death (3), myocardial infarction (12), unstable angina/ischemic ventricular fibrillation (2), stroke (3), or elevated troponin I, reflecting myocardial necrosis (25). Preoperative endothelium-dependent flow-mediated dilation was significantly lower in patients with an event (4.9±3.1%) than in those without an event (7.3±5%;P <0.001), whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups. In a Cox proportional-hazards model, the independent predictors of events were age (P =0.001), renal insufficiency (P =0.03), noncarotid surgery (P =0.05), and lower brachial artery flow-mediated dilation (P =0.007). If troponin I elevation was not considered an event, low flow-mediated dilation remained an independent predictor of risk (odds ratio 9.0, 95% CI 1.2 to 68;P =0.03). When a flow-mediated dilation cutpoint of 8.1% was used, endothelial function had a sensitivity of 95%, specificity of 37%, and negative predictive value of 98% for events. Conclusions—Impaired brachial artery endothelial function independently predicts postoperative cardiac events, which supports a role for endothelial dysfunction in the pathogenesis of cardiovascular disease. The strong negative predictive value of preserved endothelial function raises the possibility that assessment of brachial artery flow-mediated dilation will be useful in the management of patients undergoing vascular surgery.

Predictive value of noninvasivelydetermined endothelial dysfunction for long-term cardiovascular events inpatients with peripheral vascular disease ☆

Abstract Objectives The goal of this study was to prospectively examine the long-term predictive value of brachial-artery endothelial dysfunction for future cardiovascular events. Background Brachial-artery endothelial function is impaired in individuals with atherosclerosis and coronary risk factors. The prospective relation between endothelial function determined by brachial-artery ultrasound and long-term cardiovascular risk is unknown. Methods We examined brachial-artery endothelial function using ultrasound in 199 patients with peripheral arterial disease before elective vascular surgery. Patients were prospectively followed with an average follow-up of 1.2 years after surgery. Results Thirty-five patients had an event during follow-up, including cardiac death (5 patients), myocardial infarction (17 patients), unstable angina (10 patients), or stroke (3 patients). Preoperative endothelium-dependent flow-mediated dilation (FMD) was significantly lower in patients with an event (4.4 ± 2.8%) compared with those without an event (7.0 ± 4.9%, p Conclusions Impaired brachial-artery endothelial function independently predicts long-term cardiovascular events in patients with peripheral arterial disease. The findings suggest that noninvasive assessment of endothelial function using brachial-artery FMD may serve as a surrogate end point for cardiovascular risk.

Long-term Outcomes After Endovascular Abdominal Aortic Aneurysm Repair: The First Decade

Objective:The proper role of endovascular abdominal aortic aneurysm repair (EVAR) remains controversial, largely due to uncertain late results. We reviewed a 12-year experience with EVAR to document late outcomes. Methods:During the interval January 7, 1994 through December 31, 2005, 873 patients underwent EVAR utilizing 10 different stent graft devices. Primary outcomes examined included operative mortality, aneurysm rupture, aneurysm-related mortality, open surgical conversion, and late survival rates. The incidence of endoleak, migration, aneurysm enlargement, and graft patency was also determined. Finally, the need for reintervention and success of such secondary procedures were evaluated. Kaplan-Meier and multivariate methodology were used for analysis. Results:Mean patient age was 75.7 years (range, 49–99 years); 81.4% were male. Mean follow-up was 27 months; 39.3% of patients had 2 or more major comorbidities, and 19.5% would be categorized as unfit for open repair. On an intent-to-treat basis, device deployment was successful in 99.3%. Thirty-day mortality was 1.8%. By Kaplan-Meier analysis, freedom from AAA rupture was 97.6% at 5 years and 94% at 9 years. Significant risk factors for late AAA rupture included female gender (odds ratio OR, 6.9; P = 0.004) and device-related endoleak (OR, 16.06; P = 0.009). Aneurysm-related death was avoided in 96.1% of patients, with the need for any reintervention (OR, 5.7 P = 0.006), family history of aneurysmal disease (OR, 9.5; P = 0.075), and renal insufficiency (OR, 7.1; P = 0.003) among its most important predictors. 87 (10%) patients required reintervention, with 92% of such procedures being catheter-based and a success rate of 84%. Significant predictors of reintervention included use of first-generation devices (OR, 1.2; P < 0.01) and late onset endoleak (OR, 64; P < 0.001). Current generation stent grafts correlated with significantly improved outcomes. Cumulative freedom from conversion to open repair was 93.3% at 5 through 9 years, with the need for prior reintervention (OR, 16.7; P = 0.001) its most important predictor. Cumulative survival was 52% at 5 years. Conclusions:EVAR using contemporary devices is a safe, effective, and durable method to prevent AAA rupture and aneurysm-related death. Assuming suitable AAA anatomy, these data justify a broad application of EVAR across a wide spectrum of patients.

Predictive Value of Reactive Hyperemia for Cardiovascular Events in Patients With Peripheral Arterial Disease Undergoing Vascular Surgery

Objective— Reactive hyperemia is the compensatory increase in blood flow that occurs after a period of tissue ischemia, and this response is blunted in patients with cardiovascular risk factors. The predictive value of reactive hyperemia for cardiovascular events in patients with atherosclerosis and the relative importance of reactive hyperemia compared with other measures of vascular function have not been previously studied. Methods and Results— We prospectively measured reactive hyperemia and brachial artery flow-mediated dilation by ultrasound in 267 patients with peripheral arterial disease referred for vascular surgery (age 66±11 years, 26% female). Median follow-up was 309 days (range 1 to 730 days). Fifty patients (19%) had an event, including cardiac death (15), myocardial infarction (18), unstable angina (8), congestive heart failure (6), and nonhemorrhagic stroke (3). Patients with an event were older and had lower hyperemic flow velocity (75±39 versus 95±50 cm/s, P=0.009). Patients with an event also had lower flow-mediated dilation (4.5±3.0 versus 6.9±4.6%, P<0.001), and when these 2 measures of vascular function were included in the same Cox proportional hazards model, lower hyperemic flow (OR 2.7, 95% CI 1.2 to 5.9, P=0.018) and lower flow-mediated dilation (OR 4.2, 95% CI: 1.8 to 9.8, P=0.001) both predicted cardiovascular events while adjusting for other risk factors. Conclusions— Thus, lower reactive hyperemia is associated with increased cardiovascular risk in patients with peripheral arterial disease. Furthermore, flow-mediated dilation and reactive hyperemia incrementally relate to cardiovascular risk, although impaired flow-mediated dilation was the stronger predictor in this population. These findings further support the clinical relevance of vascular function measured in the microvasculature and conduit arteries in the upper extremity.

Incision and abdominal wall hernias in patients with aneurysm or occlusive aortic disease

INTRODUCTION Patients undergoing midline incision for abdominal aortic reconstruction appear to be at greater risk for postoperative incision hernia compared with patients undergoing celiotomy for general surgical procedures. Controversy exists as to whether incidence of abdominal wall hernia and increased risk for incision hernia is higher in patients with abdominal aortic aneurysm (AAA) than in patients operated on because of aortoiliac occlusive disease (AOD). We conducted a prospective multi-institutional study to assess frequency of incision hernia after aortic surgery through a midline laparotomy and of previous abdominal wall hernia. METHODS Patients with AAA (n = 177) or AOD (n = 82) from three major institutions were prospectively enrolled in the study and examined. Data collected included demographic data, cardiopulmonary risk factors, smoking status, history of previous or current abdominal wall hernia (incision, inguinal, umbilical, femoral), previous midline incision, suture type, and postoperative complications. At a minimum of 6 months after laparotomy, patients were evaluated clinically for a new incision hernia. Differences were tested with the unpaired t test, X(2) test, or Fisher exact test, and multiple logistic regression was used to control for confounding variables. RESULTS Mean follow-up of the cohort was 32.8 +/- 2.3 months. Rate of abdominal wall hernia and inguinal hernia in patients with AAA versus AOD was 38.4% versus 11% (P =.001) and 23.7% versus 6.1% (P =.003), respectively. Rate of postoperative incision hernia in patients with AAA was 28.2%, and in patients with AOD was 11.0% (P =.002). Adjusting for age, smoking, chronic obstructive pulmonary disease, body mass index, diabetes, bowel obstruction, and suture type, patients with AAA had almost a ninefold risk for postoperative incision hernia formation (odds ratio [OR], 8.8; P =.0049). CONCLUSION Compared with patients with AOD, patients with AAA have a higher frequency of abdominal wall hernia and inguinal hernia, and are at significant increased risk for development of incision hernia postoperatively. The higher frequency of hernia formation in patients with AAA suggests the presence of a structural defect within the fascia. Further studies are needed to delineate the molecular changes of the aorta and its relation to the abdominal wall fascia.

Infrapopliteal balloon angioplasty for the treatment of chronic occlusive disease

OBJECTIVE There is little documentation of the effectiveness of percutaneous balloon angioplasty (PTA) of infrapopliteal vessels for the treatment of chronic lower extremity ischemia. This study reviewed our recent experience with infrapopliteal PTA in a large series of patients to determine its effectiveness as a treatment modality. METHODS All patients undergoing primary infrapopliteal PTA from March 2002 to June 2006 were included. Primary study end points were primary patency, assisted patency, limb salvage, and patient survival assessed by Kaplan-Meier life-table analysis. Factors predictive of PTA failure and patient longevity were evaluated by multivariate methods. RESULTS There were 155 PTAs undertaken in 144 patients (70% men; mean age, 74 years), with critical limb ischemia (86%), diabetes (66%), and renal insufficiency (45%). Infrapopliteal lesions were classified as TransAtlantic Inter-Society Consensus A (7%), B (18%), C (39%), and D (35%). PTA was confined to the infrapopliteal segment in 40 (26%), and 115 (74%) underwent multilevel treatment. Five patients (3%) received stents. Technical success was 95%. The 30-day mortality was 2%, and major morbidity was 3%. The mean follow-up was 22 months (range, 0-54 months). The 40-month actuarial primary patency was 62% (standard error, 5%), with assisted patency (infrapopliteal re-PTA, 25 [16%]) of 90%. Interval conversion to bypass surgery occurred in seven (5%). Nonhealing ulcers occurred in 118 patients (76%), of which 76 (64%) healed during follow-up. Of the 42 unhealed ulcers, 15 (13%) required major amputations for a 40-month limb salvage of 86.2%. Multivariate predictors that were negative for primary patency included 0/1 vessel runoff (P = .01), critical limb ischemia (P = .002), and dialysis (P = .03). Negative predictors of limb salvage included dialysis (P = .007) and failure to improve runoff to the foot (P = .006). At 40-months, patient survival was 54%, with negative predictors including severe pulmonary disease (P = .01), coronary artery disease (P = .04), and renal insufficiency (P < .001). CONCLUSIONS Infrapopliteal angioplasty can be performed safely with favorable results in patients with limited longevity. Primary patency is related to disease extent. Secondary interventions may be necessary to maintain clinical success. These data indicate that PTA should be considered as initial therapy for infrapopliteal occlusive disease in patients with lower extremity ischemia.

Preoperative functional status predicts perioperative outcomes after infrainguinal bypass surgery

OBJECTIVE Infrainguinal surgical bypass (BPG) is a durable method for lower extremity revascularization, but is accompanied by significant 30-day morbidity and mortality (MM). The goal of this study is to relate preoperative functional status, a defined metric in the National Surgical Quality Improvement Program (NSQIP) database, to perioperative MM. METHODS Between January 1, 2005 and December 31, 2007, all patients who underwent BPG from the NSQIP private sector database were reviewed. The primary end-point was 30-day MM. Patients were stratified by preoperative functional status: independent (IND) vs dependent (DEP). Associated patient demographic/clinical data were analyzed using univariate and multivariate methods. Composite odds ratios were constructed with clusters of high-risk comorbidities. RESULTS There were 5639 BPG patients (4600 [81.6%] IND and 1039 [18.4%]) DEP. DEP patients were significantly older (71.6 +/- 11.8 vs 66.8 +/- 11.8 years; P < .0001), had more chronic obstructive pulmonary disease (COPD) (16.7% vs 11.4%; P < .0001), diabetes (54.2% vs 40.7%; P < .0001), dialysis dependence (16.4% vs 5.6%; P < .0001), and critical limb ischemia (64.6% vs 44.0%; P < .0001). DEP patients had a higher incidence of death (6.1% vs 1.5%; P < .0001) and major complications (30.3% vs 14.2%; P < .0001). DEP was an independent predictor of major complications (odds ratio [OR]: 2.0; 95% confidence interval [CI]: [1.7-2.4]; P < .0001) major systemic complications (2.5 [1.9-3.2]; P < .0001), major operative site complications (1.6 [1.4-1.9]; P < .0001) and death (2.3[1.6-3.4]; P < .0001). The combination of DEP with emergency surgery, Cr > 1.8, or rest pain increased the odds of major complications by five, seven, or 11-fold, respectively. The combination of DEP with hemodialysis, emergency surgery, or age > or = 80 years increased the odds of death by 13, 38, or 87-fold, respectively. CONCLUSION Preoperative DEP is significantly correlated with all adverse 30-day outcomes in BPG patients. Furthermore, when combined in high-risk composites with specific preoperative clinical variables, DEP is associated with prohibitive MM, thereby identifying patient cohorts that may be unsuitable for BPG.

Significant perioperative morbidity accompanies contemporary infrainguinal bypass surgery: An NSQIP report

OBJECTIVES A variety of clinical and anatomic factors influence the choice between infrainguinal bypass surgery (BPG) and percutaneous endovascular procedures (PTA) to treat lower extremity vascular disease. The decision, in part, is dependant on periprocedural morbidity. The goal of this study was to document the contemporary morbidity and mortality of infrainguinal BPG, utilizing the previously validated National Surgical Quality Improvement Program (NSQIP) database. METHODS Data from the private sector NSQIP, a prospectively validated systematic-sample database, using Current Procedural Terminology (CPT) codes for all infrainguinal BPG performed between January 1, 2005, and December 31, 2006, were analyzed. Study endpoints included 30-day death and NSQIP-defined major complications, including graft failure, differentiated between systemic vs operative-site related complications. Potentially associated clinical variables were assessed by univariate methods to create the multivariate models of factors associated with study endpoints. RESULTS There were 2404 infrainguinal BPG (infrapopliteal distal anastomosis 42%, prosthetic 29%) performed in the study interval with patient variables: age 67 +/- 12, male 66%, diabetes 44%, limb salvage indications 48%. The 30-day composite mortality/major morbidity was 19.5%. The overall mortality was 2.7% and correlated with (P value, odds ratio [OR]): patient age (<.001, 1.056), low body weight (.007, 0.988), significant preoperative dyspnea (.03, 1.97), dialysis (.003, 5.26), history transient ischemic attack (.03, 2.43), and bleeding disorder (.02, 2.01). Major complications occurred in 18.7% patients, including 7.4% graft thromboses, and 9.4% wound infections. Major systemic complications occurred in 5.9% and correlated with: age (.001, 1.03), history myocardial infarction (.02, 2.37), dialysis (<.001, 2.52), impaired sensorium (.005, 2.93), and general (vs regional) anesthesia (.04, 1.9). Major operative site-related complications occurred in 15.1% and correlated with: history chronic obstructive pulmonary disease (.04, 1.40), limb salvage indication (<.001, 1.71), impaired sensorium (.01, 2.26), non-independent preoperative functional status (.03, 1.37), and operative time (<.001, 1.002). The combination of dialysis and age >80 was identified as the most powerful high-risk composite for death (13.3-fold) and major complications (2.2-fold). CONCLUSION Infrainguinal BPG is accompanied by significant major morbidity and mortality in contemporary practice. These results reinforce the precept that stringent indications for BPG should be maintained, when considering the method of lower extremity revascularization.

Prostanoid Production in Rabbit Corpus Cavernosum: I. Regulation by Oxygen Tension

PURPOSE To investigate the effects of oxygen tension on prostanoid synthesis in rabbit penile corpus cavernosum tissue (RCC) in organ culture. MATERIALS AND METHODS Strips of rabbit corpus cavernosum were incubated in organ culture media under varying oxygen conditions (0%, 12% and 21% oxygen), in the presence or absence of acetylcholine and arachidonate stimulation. Prostanoids were measured in collected media by radioimmunoassay. Prostaglandin H synthase (PGHS) protein levels and mRNA PGHS expression were measured under both 0% and 21% oxygen conditions. RESULTS Basal and acetylcholine-stimulated PGI2 release was progressively diminished as a function of diminishing oxygen tension (pO2 from approximately 165 to 25 mm.Hg). The basal and stimulated production of other prostanoids, thromboxane A2, PGF2alpha, and PGE2, was also significantly inhibited under 0% oxygen (approximately 25 mm.Hg) conditions. However, incubation under 0% oxygen did not alter PGHS protein levels nor mRNA PGHS expression. Cavernosal strips incubated under 0% oxygen but supplemented with exogenous arachidonate (10 microM.) maintained significantly lower PGI2 production than tissues exposed to 21% oxygen (approximately 165 mm.Hg). CONCLUSIONS These data demonstrate that oxygen tension regulates prostaglandin production in corporal tissue. The reduction in prostanoid production during hypoxia can be attributed to inhibition of PGHS activity rather than the expression of the enzyme. In view of the role of PGI2 as an inhibitor of platelet aggregation and white cell-endothelial adhesion, our findings may provide mechanistic insight into the alteration in corporal blood homeostasis ischemic-hypoxic priapism.

A noninvasive murine model of hind limb ischemia-reperfusion injury.

BACKGROUND This study describes a novel murine method of the Controlled Tension Tourniquet (CTT). The CTT applies a measured circumferential tension to hind limbs using a tourniquet attached to digital strain gauges, and is useful for investigating hind limb ischemia reperfusion (IR). MATERIALS AND METHODS Mice were subjected to 1, 3, or 6 h of unilateral hind limb ischemia followed by either 4 or 24 h of reperfusion. Blood flow in the ischemic, reperfused, and contralateral limbs was monitored using a Laser Doppler Imager. Edema in the IR limbs was documented by changes in the wet weight to dry weight ratio. Myeloperoxidase and tetrazolium based mitochondrial activity assays indicated neutrophil infiltration and tissue viability, respectively. RESULTS During reperfusion following 1, 4, or 6 h, flow stabilized at 100%, 53%, and 23% of baseline levels, respectively. Edema was present all in IR limbs after 4 h of reperfusion, but increased with the duration of ischemia. After 24 h of reperfusion neutrophil infiltration was equivalent in all IR limbs after all intervals of ischemia. After 24 h of reperfusion, tissue viability after 1 h of ischemia was equivalent to sham or contralateral limbs. At 3 or 6 h of ischemia and 24 h reperfusion decreased tissue viability to 40% of sham and contralateral limbs. CONCLUSIONS The CTT provides a reproducible, noninvasive model of acute limb ischemia, which reflects the biochemical indices of microvascular injury, inflammation and flow characteristic of reperfusion injury.