Cardiac risk factors of revascularization in chronic atherosclerotic lower extremity ischemia.

PURPOSE: To identify the risk factors of major adverse cardiac event (MACE) in patients with chronic atherosclerotic lower extremity ischemia (CALEI) undergoing revascularization without noninvasive stress testing (NIST).
METHODS: From January 2007 to January 2012, patients with CALEI who underwent revascularization were retrospectively reviewed. Emergent operations, revision procedures for previous surgery, or patients with active cardiac conditions were excluded. NIST was not performed for patients without active cardiac conditions. Cardiac risk was categorized into low, intermediate and high risk, according to the Lee's revised cardiac risk index. MACE was defined as acute myocardial infarction or any cardiac death within 30 days after surgery.
RESULTS: A total of 459 patients underwent elective lower extremity revascularization procedures (240 open surgeries, 128 endovascular procedures, and 91 hybrid surgeries). The treated lesions comprised of 18% aorto-iliac, 58% infrainguinal, and 24% combined lesions. With regard to cardiac risk, low-, intermediate- and high risks were 67%, 32% and 2%, respectively. MACE was developed in 7 patients (2%). High or intermediate risk group by the Lee's index was related to postoperative MACE. Subgroup analysis for open surgery or hybrid surgery group identified female gender as an independent risk factor of MACE (P = 0.049; odds ratio, 5.168; confidence interval, 1.011 to 26.423).
CONCLUSION: The Lee's index was a useful predictor of MACE. MACE is more common in female patients than male patients after open or hybrid surgery. Routine preoperative NIST is not suggested for all patients undergoing revascularization for CALEI, especially for those in the low risk group.

INTRODUCTION

Cardiac complications are important causes of morbidity and mortality in vascular surgery, and the reported rate of cardiac morbidity is often greater than 5% [1]. For these reasons, preoperative cardiac risk evaluation is an important part of vascular surgery. The American College of Cardiology (ACC) and the American Heart Association (AHA) introduced guidelines to detect and manage perioperative cardiac risk and to prevent cardiac complications after vascular surgery [2]. For preoperative noninvasive stress testing (NIST), the guidelines recommended that patients with active cardiac conditions (Table 1) should be evaluated and treated (class I). Patients who do not have active cardiac conditions are stratified into 3 groups by the Lee's revised cardiac risk index (Table 2) [3]. NIST may be considered for patients with high (class IIa) or intermediate (class IIb) risk, if it will change management.

Table 1

Active cardiac conditions

CCS, Canadian Cardiovascular Society; MI, myocardial infarction; HF, heart failure; NYHA, New York Heart Association; HR, heart rate.

a)According to Campeau [4]. b)May include "stable" angina in patients who are unusually sedentary. c)The American College of Cardiology National Database Library defines recent MI as more than 7 days but less than or equal to 1 month (within 30 days).

Table 2

The Lee's revised cardiac risk index categorizes the risk of cardiac events in patients undergoing surgery

a)The Lee's index uses six criteria: high-risk surgery, ischemic heart disease, congestive heart failure, cerebrovascular disease, insulin-dependent diabetes mellitus, and renal failure [3].

However, in practice, NIST is sometimes performed without considering patient conditions. This study was aimed to identify the risk factors of postoperative major adverse cardiac event (MACE) when NIST is not performed before revascularization in chronic atherosclerotic lower extremity ischemia (CALEI).

METHODS

Patients

From January 2007 to January 2012, all patients with CALEI who underwent revascularization procedures in Daegu Catholic University Medical Center were retrospectively reviewed. Excluding emergent or urgent operations, nonatherosclerotic etiology, revision procedures for previous vascular or endovascular surgery or active cardiac conditions, 459 patients were enrolled in this study.

Patient demographic data, coexisting disease and treatment factors including procedure type (open surgery, endovascular treatment, and hybrid surgery), treated lesions and operation time were investigated. According to the Lee's index, patients were categorized into 3 groups (low-, intermediate-, and high-risk group).

Preoperative cardiac evaluation

First, careful history taking was done to identify prior angina pectoris or myocardiac infarction, heart failure, arrhythmia and valvular heart disease. Physical examination, routine blood test, electrocardiography (ECG), chest X-ray and echocardiography were performed routinely. However, NIST (e.g., exercise ECG, adenosine MIBI scan and so on) or coronary angiography was not part of the routine examination. The only indication of NIST or coronary angiography was active cardiac conditions.

Definitions and outcome assessment

Acute myocardiac infarction (AMI) was defined as the presence of 2 or more of the following 3 criteria: 1) typical chest pain, 2) elevated cardiac enzyme, and 3) typical change in serial ECG. MACE was defined as AMI or any cardiac death after treatment. Primary outcome was MACE occurring within 30 days after treatment.

Statistics

To identify the independent risk factors of MACE, univariate and multivariate analyses were performed using the SPSS ver. 12.0.1 (SPSS Inc., Chicago, IL, USA). The association between categorical clinical variables and MACE was analyzed by the chi-square test or Fisher exact test. Binary logistic regression model was used for multivariate analysis. P-value < 0.05 was considered statistically significant.

RESULTS

A total of 459 patients underwent elective lower extremity revascularization procedures for CALEI during the study period. The mean age of patients was 69 years (range, 42 to 93 years) and 83% was male. Forty percent of patients had critical limb ischemia. Regarding the Lee's index, 67% of patients were at low risk, 32% intermediate risk, and 2% high risk. Other patient demographic data are shown in Table 3.

Table 3

Patient characteristics (n = 459)

Values are presented as mean (range) or number (%).

All procedures were done by two vascular surgeons. Treatment details are summarized in Table 4. The mean operation time was 181 minutes. The treated lesions comprised of 18% aorto-iliac, 58% infrainguinal, and 24% combined lesions. Fifty-two percent of the cases were open surgery, 28% were endovascular treatment and 20% were hybrid surgery.

Table 4

Treatment details

Values are presented as mean (range) or number (%).

Seven patients (1.5%) had a MACE. AMI developed in 6 patients. There were 5 cardiac deaths due to AMI (4 patients) and congestive heart failure (1 patient). All MACE occurred in patients who underwent open or hybrid surgery (2.1%, 7/331). There was no MACE in the endovascular treatment group.

On univariate analysis, female gender, ischemic heart disease, congestive heart failure, ejection fraction <50%, left ventricular wall motion abnormality in echocardiography, intermediate or high risk by the Lee's index showed association with MACE (Table 5). However, no independent risk factors of postoperative MACE were determined by the binary logistic regression model (Table 6).

Table 5

Univariate analysis

Values are presented as number (%).

MACE, major adverse cardiac event.

a)According to the Lee's revised cardiac risk index.

Table 6

Multivariate analysis

OR, odds ratio; CI, confidence interval.

Subgroup analysis was done excluding the endovascular treatment group that had no MACE (Tables 7, 8). Female gender was identified as an independent risk factor of postoperative MACE (P = 0.049; odds ratio [OR], 5.168; confidence interval [CI], 1.011 to 26.423) besides the Lee's index.

Table 7

Univariate analysis, subgroup analysis

Values are presented as number (%).

MACE, major adverse cardiac event.

a)According to the Lee's revised cardiac risk index.

Table 8

Multivariate analysis, subgroup analysis

OR, odds ratio; CI, confidence interval.

DISCUSSION

Peripheral arterial disease (PAD) is one of the clinical manifestations of systemic atherosclerosis. Therefore, a significant portion of PAD patients have coexisting or subclinical coronary artery disease (CAD). In a multicenter, cross-sectional PAD detecting program in the United States (US), the prevalence of CAD in PAD patients was 52.9% [5]. In the Reduction of Atherothrombosis for Continued Health Registry, 51.6% of PAD patients had a concomitant CAD [6]. This means that modification of atherosclerotic risk factors is important in the long term and perioperative cardiovascular risk is high in the short term.

In the US, the ACC/AHA guidelines for perioperative cardiovascular evaluation for noncardiac surgery were first introduced in 1996 and updated two times in 2002 and 2007 [2,7,8]. One of the changes was the role of NIST. In 1996, a reversible defect on NIST was considered a predictor of postoperative MACE, and CAG with possible revascularization was recommended. However, the 2002 guidelines announced that indications of preoperative PCI for noncardiac surgery are similar to those of PCI in general because there were no controlled trials comparing perioperative cardiac outcomes for patients treated with preoperative PCI versus medical therapy.

The second multicenter Dutch Echoardiographic Cardiac Risk Evaluation study assessed the value of NIST in intermediate risk patients [9]. All patients received beta-blockers to achieve a resting heart rate of 60 to 65 beats/min. There was no difference between the no NIST group and NIST group in cardiac death or MI at 30-days after surgery (1.8% vs. 2.3%, P = 0.62). In 2004, the Coronary Artery Revascularization Prophylaxis trial was published [10]. The study randomly assigned 510 patients scheduled for vascular surgery into the following two groups: coronary artery revascularization before surgery versus no revascularization before surgery. The rate of postoperative MI, defined by the elevated troponin level, was not different (12% vs. 14%, P = 0.37). Regarding the long-term outcome, mortality rate was not different at 2.7 years after randomization, (22% vs. 23%, P = 0.92).

In the revised ACC/AHA 2007 guidelines [2] based on the above mentioned trials, the only class I recommendations of NIST are active cardiac conditions (unstable coronary syndromes, decompensated heart failure, significant arrhythmias and severe valvular disease). Moreover, coronary revascularization is no longer recommended before surgery for patients with stable CAD. The European Society of Cardiology guidelines [11] have been recently published and they are not different to the ACC/AHA guidelines.

Our policy is not different from the guidelines. NIST or CAG are considered only for patients with active cardiac conditions. In our recent retrospective review of 459 patients who underwent revascularization for CALEI without preoperative NIST, 66% were at low risk, 32% at intermediate risk and 2% at high risk. MACE was 1.5% which was not higher than previous reports. Because high risk group was only 2%, it is assumed that routine NIST is not necessary at least for intermediate and low risk patients. There was no MACE after endovascular treatment. Multivariate analysis failed to identify the risk factors of postoperative MACE. Subgroup analysis of the open or hybrid surgery group showed that female gender was the only significant risk factor of MACE after surgery (P = 0.049; OR, 5.168; CI, 1.011 to 26.423).

In this study, the intermediate or high risk group was related to postoperative MACE by univariate analysis. Although the Lee's index has been widely used to assess perioperative cardiac risk since its first introduction in 1999, it still has some limitations. Ford et al. [12] conducted a meta-analysis of 24 studies that reported the association of the Lee's index with MACE or death in the hospital or within 30 days of surgery. In their systemic review, the Lee's index discriminated moderately well between patients at low versus high risk for cardiac events after mixed noncardiac surgery. However, its performance was considerably diminished when it was used in patients who underwent vascular noncardiac surgery. They emphasized the necessity of high-quality research in perioperative medicine.

For these reasons, many researchers are trying to find predictors of perioperative cardiac complications. Welten et al. [13] pointed out a limitation of the Lee's index. They claimed that the Lee's index does not include patient age. They announced that the prognostic value of the Lee's index was reduced in elderly patients (>75 years), based on the retrospective analysis of 2,642 patients who had undergone vascular surgery. They suggested that the revised risk of operation (low, low-intermediate, high-intermediate and high-risk procedures) and hypertension could improve the prediction of MACE as well as age.

The Vascular Study Group of New England (VSGNE) proposed a new cardiac risk prediction model specifically for vascular surgery patients [14]. Besides the 6 risk factors of the Lee's index, the VSGNE model included additional risk factors of increasing age, smoking, chronic obstructive pulmonary disease, abnormal preoperative cardiac stress test, and long-term beta-blocker treatment. The authors reported that the Lee's index underestimated in-hospital cardiac events in patients undergoing vascular surgery and their new index was more accurate than the Lee's index in predicting postoperative cardiac events.

Based on our results, the Lee's index was a significant predictor of postoperative MACE and female patients have a higher risk of MACE than male patients after open or hybrid surgery. Routine preoperative NIST is not necessary in all patients undergoing revascularization for CALEI, especially for patients in the low risk group and for those undergoing endovascular treatment.

Besides the small number of high risk patients, our study has several limitations. The most important one is the retrospective design of the study. Also, we did not include a treatment group who underwent NIST. Therefore, it is impossible to compare no NIST group and the NIST group. However, we think that this study has significance as a large observational study of patients with CALEI in Korea.