Ihab N. Aziz, MD, Jason T. Lee, MD, George E. Kopchok, BS, Carlos E. Donayre, MD, Rodney A. White, MD, and Christian de Virgilio, MD, Torrance, Calif

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1 Cardiac risk stratification in patients undergoing endoluminal graft repair of abdominal aortic aneurysm: A single-institution experience with 365 patients Ihab N. Aziz, MD, Jason T. Lee, MD, George E. Kopchok, BS, Carlos E. Donayre, MD, Rodney A. White, MD, and Christian de Virgilio, MD, Torrance, Calif Objective: Patients undergoing abdominal aortic aneurysm repair have a high incidence of coexisting cardiac disease. The traditional cardiac risk stratification for open abdominal aortic aneurysm surgery may not apply to patients undergoing endoluminal graft exclusion. The purpose of this study was to examine predictive risk factors for perioperative cardiac events. Methods: As part of multiple prospective endograft trials approved by the US Food and Drug Administration, data for 365 patients who underwent endoluminal graft repair from 1996 to 2001 were collected. Variables included for analysis were age and sex; history of smoking; presence of hypertension, diabetes mellitus, or renal insufficiency; Eagle clinical cardiac risk factors; American Society of Anesthesiologists index; type of anesthesia administered; estimated blood loss; preoperative hemoglobin level; preoperative use of -blocker therapy; duration of surgery; need for iliac artery conduit; and concomitant other vascular procedures. Univariate and multivariate logistic regression analysis were used to determine which variables were predictive of an adverse perioperative cardiac event, eg, Q wave and non Q wave myocardial infarction (MI), congestive heart failure (CHF), severe arrhythmia, and unstable angina. Results: The study cohort included 322 men and 43 women (mean age, 74.2 years). Fifty-two (14.2%) postoperative cardiac events occurred: severe dysrhythmia in 15 patients (4.1%), MI in 14 patients (3.8%), non Q wave MI in 8 patients (2.2%), CHF in 8 patients (2.2%), and unstable angina in 7 patients (1.9%). Univariate analysis demonstrated that age 70 years or older (P.034), history of MI (P.018), angina (P.004), history of CHF (P <.001), two or more Eagle risk factors (P <.001), and lack of use of preoperative -blocker therapy (P.005) were predictors of perioperative cardiac events. Multivariate analysis identified only age 70 years or older (P.026), history of MI (P.024) or CHF (P.001), and lack of use of preoperative -blocker therapy (P.007) as independent risk factors for an adverse cardiac event. Conclusions: Age 70 years or older, history of MI or CHF, and lack of use of preoperative -blocker therapy are independent risk factors for perioperative cardiac events in patients undergoing endoluminal graft repair. (J Vasc Surg 2003;38:56-60.) From the Division of Vascular Surgery, Harbor-UCLA Medical Center. Competition of interest: none. Presented at the Seventeenth Annual Meeting of the Western Vascular Society, Newport Beach, Calif, Sep 22-25, Reprint requests: Christian de Virgilio, MD, Division of Vascular Surgery, Harbor-UCLA Medical Center, 1000 W Carson St, Box 25 Torrance, CA ( cdevirgilio@rei.edu). Copyright 2003 by The Society for Vascular Surgery and The American Association for Vascular Surgery /2003/$ doi: /s (03) Increased demand for less invasive surgery has resulted in the emergence of endoluminal graft repair of abdominal aortic aneurysm (AAA) as an alternative to open abdominal repair. Several studies have reported the feasibility and potentially low operative morbidity of this less invasive procedure, 1-4 even in patients at high risk. 5 Open AAA repair is associated with 4% to 10% mortality These mortality rates have been challenged recently in the Aneurysm Detection and Management (ADAM) trial from the United States, with only 2.7% overall operative mortality rate. 11 Coronary artery disease is the most prominent risk factor, accounting for up to 60% of perioperative deaths. 7,8,12-14 This proportionately high cardiac morbidity can be explained by several factors. Angiographic studies have shown that 60% of patients with AAA have severe coronary artery disease. 15 Perioperative myocardial stress is exacerbated by the depressant effects of anesthetics, cross clamping of the aorta, blood loss, and associated hemodynamic and metabolic changes. 16,17 Risk stratification for cardiac events after open AAA repair has been studied by numerous authors Fewer data are available for risk stratification after endoluminal graft repair. Most studies to date suggest that cardiac morbidity and overall mortality for open and endoluminal graft repair are comparable. 1,2,4,26 Nevertheless, differences in stratification may exist, because endoluminal graft repair may impose less myocardial and hemodynamic stress than with open AAA repair. The purpose of this study was to determine which preoperative and operative variables were predictive of perioperative cardiac events. METHODS Study patients included those enrolled in one of multiple prospective trials approved by the US Food and Drug

2 JOURNAL OF VASCULAR SURGERY Volume 38, Number 1 Aziz et al 57 Administration (FDA) and those who underwent surgery after FDA approval. The procedures were performed at our institution from June 1996 through June 2001, and included Phase I (n 24), Phase II (n 74), and Phase III (n 91) trials of the AneuRx bifurcated prosthesis (Medtronic AVE, Santa Rosa, Calif); Phase I (n 46) of the Talent bifurcated prosthesis (Medtronic World Medical, Sunrise, Fla); and Phase I (n 9) and Phase II (n 25) of the Endologix bifurcated device (Endologix, Phoenix, Ariz). Data for 96 procedures in which the AneuRx device was placed post-fda approval were also included in the analysis. Patients were enrolled in a protocol approved by the Institutional Review Board of our medical center, and signed consent forms were obtained for the investigational devices and the postoperative imaging surveillance protocols. The data were prospectively entered into a database, and the records for these 365 consecutive patients (322 men, 43 women; mean age, years) were reviewed for this study. Variables examined included age and sex; history of smoking; presence of hypertension, diabetes mellitus, or renal insufficiency; clinical cardiac risk factors as described by Eagle et al, 27 ie, diabetes, age older than 70 years, angina, previous myocardial infarction (MI) by history or by Q wave on electrocardiogram (ECG), and history of congestive heart failure (CHF); American Society of Anesthesiologists index; type of anesthetic administered; estimated blood loss; preoperative hemoglobin level; preoperative -blocker therapy; duration of surgery; need for iliac artery conduit; concomitant other vascular procedures; and postoperative cardiac events. Perioperative cardiac complications were defined as occurring within 30 days of surgery or during the hospital admission. Cardiac events were defined as Q wave and non Q wave MI, CHF, unstable angina, ventricular arrhythmia, heart block, and cardiac death. MI was defined as including two or more of the following criteria: cardiac enzyme levels more than 5% or troponin concentration greater than 1.3, ECG ischemic changes, or chest pain for more than 30 minutes. Non Q wave MI was defined as elevated cardiac enzyme levels with no ECG changes. As a routine part of the studies protocol, creatine kinase MB and troponin concentrations, and ECG were obtained every 8 hours for the first 24 hours; all patients underwent the same postoperative screening to avert missed silent MI. CHF was defined as symptoms or signs of pulmonary edema or of right or left ventricular failure, and abnormal chest x-ray. Ventricular tachycardia was defined as premature ventricular contractions lasting for more than 30 seconds, more than 30 beats, and resulting in hemodynamic compromise. Unstable angina was defined as typical chest pain lasting for more than 30 minutes and relieved by rest or nitroglycerine. Renal insufficiency was defined as preoperative serum creatinine concentration greater than 1.5 mg/dl. Routine preoperative cardiac stress testing was not performed in the study patients. The 365 patients were divided into two groups, 52 patients with a postoperative cardiac event and 313 who did Table I. Preoperative data for 365 patients Factor n % Male gender Age Smoking status History of myocardial infarction Diabetes mellitus Chronic renal failure 22 6 Congestive heart failure 33 9 Angina History of hypertension Preoperative -blocker therapy not sustain a postoperative cardiac event. Variables were compared between the two groups to establish predictors of cardiac events with 2 or Fisher exact test, where appropriate. Continuous variables were compared with the Wilcoxon rank-sum test. Variables found to be significant at univariate analysis were entered into a multivariate logistic regression analysis. P.05 was considered statistically significant. All statistical analysis was performed with Systat 8.0 for Windows (SPSS Inc, Chicago, Ill). RESULTS Data for 365 patients (322 men, 43 women; mean age, 74.2 years) were included in the analysis. Patient demographic data and comorbid conditions are shown in Table I. The most frequent clinical cardiac risk factor was age older than 70 years, present in 72% of patients. There were 52 (14.2%) postoperative cardiac events, including MI in 14 patients (3.8%), arrhythmia in 12 patients (3.3%), non Q wave MI in 8 patients (2.2%), CHF in 8 patients (2.2%), angina in 7 patients (1.9%), and heart block in 3 patients (0.8%). Univariate analysis demonstrated that age 70 years or older (P.034), history of MI (P.018), angina (P.004), history of CHF (P.001), two or more Eagle risk factors (P.001), and lack of use of preoperative -blocker therapy (P.005) were predictors of postoperative cardiac events (Table II). Cardiac event rate by number of Eagle risk factors is presented in Table III. On the other hand, preoperative hemoglobin and serum creatinine concentrations, American Society of Anesthesiologists score, operative time, type of device used, gender, need for placement of a conduit, concomitant vascular procedure, diabetes, hypertension, preoperative renal insufficiency, history of smoking, type of anesthetic administrered, and number of stents used were not predictive of postoperative cardiac events. At multivariate analysis, only age 70 years or older (P.032), history of MI (P.025), history of CHF (P.002), and lack of use of preoperative -blocker therapy (P.027) were independent risk factors for a postoperative cardiac event. Table IV shows the odds ratios for the various independent risk factors. The cardiac event rate based on the number of independent risk factors present is listed in Table V. The cardiac event rate for patients with four risk factors was 50%, compared with 5.3% in patients with no risk factors.

3 58 Aziz et al JOURNAL OF VASCULAR SURGERY July 2003 Table II. Univariate analysis of cardiac events Variable Cardiac events (n 52) No cardiac events (n 313) n % n % Female gender Age History of MI Angina History of CHF Diabetes mellitus Hypertension Renal insufficiency Smoking Lack of use of -blocker Use of conduit Concomitant vascular procedure MI, Myocardial infarction; CHF, congestive heart failure. Table III. Cardiac events by number of Eagle risk factors* Number of Eagle criteria Ten patients (2.7%) died in the first postoperative 30 days or during the hospital stay. Cardiac events were the direct cause of death in 4 patients (1.1%). The presence of two or more Eagle risk factors (P.002) and need for concomitant vascular procedure (P.003) were the only variables predictive of cardiac death. DISCUSSION Endoluminal graft repair of AAA is a less invasive technique than standard open repair and is thus theoretically appealing in patients at high risk. This is supported by studies that demonstrate that endoluminal graft repair is less hemodynamically stressful than open repair. Cuypers et P Cardiac events n % 0 3/ / / / / /1 100 Total 52/ *P.001. Table IV. Odds ratio for independent risk factors Odds ratio 95% confidence interval Age Myocardial infarction Congestive heart failure Lack of use of -blockers P Table V. Cardiac event rate by number of risk factors No. of risk factors Patients (N 365) Cardiac event rate (%) al 28 reported that open repair caused a greater decrease in systemic vascular resistance as compared with endoluminal graft repair. Stroke work index, a measure of myocardial performance, diminished when the aorta was occluded during open repair and increased during endoluminal graft repair. Despite the less severe hemodynamic changes associated with endoluminal graft repair, postoperative clinical cardiac complications were the same for both endoluminal graft and open repair Similarly, de Virgilio et al 26 found no difference in cardiac complication rates or mortality when comparing endoluminal graft repair with open repair. In the present study cardiac morbidity was 14.2%. This relatively high morbidity rate may be due to our definition of cardiac events, which is broader and more inclusive than that of other studies. Overall mortality was 2.7%, whereas cardiac mortality was only 1.1%. This mortality rate is at the low end of the range of published cardiac mortality rates for open repair (2.7%-10%) The less invasive nature of endoluminal graft repair would suggest that standard methods for cardiac risk stratification might not be applicable. Although cardiac risk stratification for open AAA repair has been studied extensively, fewer data are available for endoluminal graft repair. The present study confirms the utility of clinical cardiac risk factors (age 70 years, history of MI or CHF) as independent predictors of adverse perioperative cardiac events. Previous MI or CHF is an important clinical predictor of cardiac morbidity after endoluminal graft repair. 25 Other variables, including female gender and elevated serum creatinine concentration, are important predictors of mortality after open AAA repair. Katz et al 31 showed that mortality in female patients undergoing open repair are higher than in male patients. Crawford et al 32 and Dardik et al 33 reported similar results. This concept was challenged by Johnston et al, 34 Wolf et al, 35 and Mathison et al, 36 who showed no difference in postoperative overall mortality or complications between male and female patients. In the present study we found no difference in rate of cardiac events between men (13%) and women (21%) (P.182). Similarly, in another study 34 serum creatinine value was a predictor of outcome; in the present study, mean serum creatinine concentration in patients with cardiac events (1.34 mg/dl) was not different from that in patients without cardiac events (1.28 mg/dl; P.32). However, the low frequency of both variables might have created a statistical error in this study. While multiple reports 27,38 proposed use of clinical markers for cardiac risk stratification, others 39,40 have ar-

4 JOURNAL OF VASCULAR SURGERY Volume 38, Number 1 Aziz et al 59 gued that clinical assessment alone fails to detect significant coronary artery disease in patients unable to exercise and fails to predict cardiac events. In our two previous studies, 41,42 we found that no individual Eagle criterion was predictive of adverse cardiac events in patients undergoing major elective vascular surgery. In a more recent study that focused on patients undergoing open and endoluminal graft repair of AAA, history of CHF and Q wave on ECG were the only Eagle criteria predictive of postoperative cardiac events. 26 The present study confirmed the importance of age older than 70 years and history of MI or CHF as independent predictors for cardiac events (Table II). The study also demonstrates a stepwise increase in cardiac risk as the number of risk factors increases (Table V). Perioperative use of -blockers reduces the incidence of cardiac complications after major vascular surgery In a randomized study of patients at high cardiac risk (positive dobutamine ECG and 1 or more Eagle risk factors) undergoing major vascular surgery, Poldermans et al 45 demonstrated that use of bisoprolol significantly reduced the rate of nonfatal perioperative MI from 17% to 0% and reduced cardiac mortality from 17% to 3.4%, when compared with patients not receiving a -blocker. The role of perioperative -blockade for patients undergoing endoluminal graft repair of AAA is not well defined. Given the less invasive nature of endoluminal graft repair and studies demonstrating that this procedure causes less hemodynamic stress, one might expect a lack of benefit to adding -blockade in these patients. In the present study, 243 patients (67%) were receiving -blockers preoperatively; only 27 patients (11.1%) had cardiac events, compared with 17 of 69 patients (24.6%) who did not receive preoperative -blocker therapy (P.004). Significantly, at multivariate analysis the lack of perioperative -blockade was an independent predictor for an adverse cardiac event. The role of cardiac risk assessment and coronary revascularization before major vascular surgery remains controversial. Our current practice is to strictly limit cardiac stress testing and coronary revascularization to patients with recent or severe cardiac symptoms. This approach is supported by the overall low cardiac mortality (1.1%) reported in this series. However, given the high cardiac event rate noted in this study for patients with multiple risk factors (history of MI or CHF, and age older than 70 years), consideration should be given to stress testing in this highly selected subgroup of patients. In conclusion, the present study reports 14.2% cardiac morbidity, 1.1% cardiac mortality, and 2.7% overall mortality in a series of 365 consecutive patients undergoing endoluminal graft repair of AAA. The study confirmed the importance of the presence of multiple clinical risk factors (history of MI or CHF, age older than 70 years) as predictors of adverse cardiac events. Furthermore, the study demonstrated that use of perioperative -blockade is important during endoluminal graft repair, although this procedure is less hemodynamically stressful than open repair. For patients with multiple cardiac risk factors, it is yet to be determined whether the addition of -blockade is sufficient cardiac protection or whether additional cardiac stress testing with coronary revascularization is needed. REFERENCES 1. Zarins CK, White RA, Schwarten D, et al, for the investigators of the Medtronic AneuRx Multicenter Clinical Trial. 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