Cardiac complications after surgery.

Don Poldermans.

Department of Vascular Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands

Summary

Cardiac complications are the major cause of perioperative and late mortality and morbidity in patients undergoing infrarenal aortic surgery. This is related to the presence of underlying coronary artery disease (CAD). CAD may be asymptomatic because of reduced exercise capacity due to non-cardiac diseases like stroke or claudication. Careful preoperative evaluation and management of cardiac risk factors offers the physician a unique opportunity to improve patients’ perioperative and long-term outcome.

1.1 The clinical problem

Peripheral vascular disease is an increasing problem in Europe and in North America. For example, between 1980 and 1995 in the Netherlands, the number of patients admitted to hospital because of peripheral vascular disease (PVD) increased from 17,511 to 29,346, which is an increase of 36% after correction for demographic factors [1]. The high incidence of PVD was confirmed in a recent study from the UK, which used ultrasound screening to show that between 1.5 and 3% of men older than 60 years had an occult aortic aneurysm between 40 and 59 mm of diameter [2]. A large number of these patients will require surgery, as the optimal treatment of an occult aortic aneurysm is elective surgery if the diameter exceeds 50 mm [2]. Although the incidence of perioperative cardiac death and myocardial infarction (MI) of elective surgery has decreased gradually over time [Figure 1], 30 day operative mortality is still 5–6% and five year mortality is 45%, both of which arise principally from cardiac events [3].

The aim of the treating physician is not only that patients should emerge from the operation intact but they should also survive long enough to enjoy the benefits of the surgery. Therefore, it is mandatory that the treating physician evaluates the presence and extent of CAD as well as other cardiac risk factors, like hypertension, smoking, diabetes mellitus, and hyperlipedemia that will determine long-term survival after surgery.

1.2 Pathophysiology

Perioperative cardiac events are mainly caused by myocardial ischemia, and most of these occur on the second or third postoperative day [3]. The ischemia may arise either from increased myocardial oxygen demand or reduced supply. Tachycardia and hypertension resulting from surgical stress, pain, interruption of beta-blockers, or the use of sympathomimetic drugs all increase myocardial oxygen demand. Decreased supply may be the result of hypotension, vasospasm, anaemia, hypoxia, or plaque rupture with thrombosis.

The location of the perioperative MI is not always related to the location of the culprit coronary lesion. In a population of 32 patients who died within 30 days after major vascular surgery the location(s) of the culprit coronary lesion assessed preoperatively by dobutamine echocardiography (DE) was compared to the location of the MI at autopsy [4]. DE showed myocardial ischemia in 16 patients, in 7 patients in multiple coronary regions. In 36% of patients DE did not predict the location of the perioperative MI. This may indicate that CAD occurs diffuse in the coronary tree and factors like stress and thrombosis can boost a (subclinical) coronary stenosis. Long-term cardiac complications are more common in the presence of left ventricular (LV) dysfunction and myocardial ischemia [5].

2. Preoperative cardiac risk assessment

2. 1. Identification of high-risk patients

Risk stratification begins with the assessment of clinical history and knowledge of the surgical procedure to be performed. A number of risk indices have been developed over the past two decades, such as the Goldman cardiac risk index, the Detsky modified multifactorial risk index, and Eagle’s risk score [3,6,7]. These risk indices allow stratifying patients into low, intermediate, or high risk for cardiac complications. Recently, Lee et al [8] have reviewed the predictive value of several clinical risk factors in patients scheduled for non-cardiac surgery. Six risk factors [high-risk type of surgery, stroke, diabetes mellitus, renal failure, heart failure, and ischemic heart disease] were identified in a study population of 2893 patients and later validated in a population of 1422 patients. The rate of major perioperative complications in the presence of 0, 1, 2, or ³ 3 risk factors was 0.4%, 0.9%, 7%, and 11%, respectively. However, the limitation of this study was that only 3.8% (110 of 2893) of the study population underwent major vascular surgery.

Patients with no cardiac risk factors are generally at low risk and need no further risk evaluation or therapy. The occurrence of ischemia on stress testing has a low predictive value in such patients and may be associated with more false positive than true positive results [9]. In the case of patients with one or more cardiac risk factors (angina pectoris, previous myocardial infarction, diabetes mellitus, congestive heart failure, cardiac arrhythmias, age >70 years, renal failure [creatinine clearance <65 ml/min]) or for patients with reduced exercise capacity additional non-invasive testing is recommended. The least expensive non-invasive test for myocardial ischemia is exercise electrocardiography. It can be safely performed in outpatient settings. Pooled data from seven studies indicate that exercise electrocardiography has a sensitivity for the prediction of cardiac death and myocardial infarction of 74% and a specificity of 69%. However, several drugs can influence the results of exercise electrocardiography, including digitalis use, beta-blockers, vasodilators and other antihypertensive agents. Ideally, in order to perform the test these medications should be withdrawn, which is often not feasible. Moreover, the presence of resting ECG changes (bundle branch block, left ventricular hypertrophy and digitalis use) may preclude reliable ST-segment analysis in 40% of patients [10]. In patients unable to perform adequate exercise (and most vascular surgical patients unable to exercise), a nonexercise test is mandatory. In this regard, dipyridamole perfusion imaging, often with combination of clinical risk assessment is the most extensively studied non-invasive approach to the cardiac risk stratification. The test provides information beyond that available from clinical evaluations and exercise electrocardiography [11, 12]. Pooled data from 24 studies indicate that dipyridamole perfusion imaging has a sensitivity for the prediction of adverse perioperative cardiac events of 83% and a specificity of 49%. The limitation to this test is that false positive results are an important problem, particularly with SPECT. Attenuation artefacts such as, breast tissue and the diaphragm can produce apparent perfusion defects.

Dobutamine-atropine echocardiography is a new tool for preoperative and late cardiac risk assessment. The test detects inducible myocardial ischemia and resting LV dysfunction [13], which are known to be predictors of perioperative ischemic complications and late cardiac death. It can also detect unsuspected valve disease and this may be relevant. Second harmonic imaging has improved the accuracy of endocardial delineation [14], and it will likely reduce intra- and interobserver variability that is one of the major limitations of DE.

The technique is safe. In a recent review of 6595 stress tests [15-17], the incidence of cardiac arrhythmias and hypotension was, respectively, 8% and 3%. Pellikka et al [18] confirmed the safety and feasibility of dobutamine echocardiography in 98 patients with aortic aneurysm. There were no cases of aneurysm rupture or hemodynamic instability. Thus, the complication rate of DE is comparable to that of dipyridamole perfusion scintigraphy [19] and exercise ECG [20].

2. 2. Comparison of perfusion imaging and echocardiography

Unfortunately, there has been no direct comparison of these techniques in perioperative risk assessment, although preliminary data in 43 patients suggest that both dipyridamole perfusion imaging and dipyridamole echocardiography have a high negative predictive value (88% versus 94%), but dipyridamole echocardiography has a higher positive predictive accuracy (37% versus 67%) [21]. The meta-analysis of Shaw et al [22] also compares dipyridamole perfusion imaging and DE, although not in the same patients. Both tests had comparable predictive accuracy although the summed odds ratios for cardiac death and myocardial infarction were greater for DE than for dipyridamole perfusion imaging. However, the confidence intervals for the echocardiography tests were large because of the smaller number of patients. Recently we compared the predictive value of six non-invasive tests using an innovative meta-analytic approach [23]. Our results demonstrated that pharmacological stress tests exhibited higher overall sensitivity and specificity compared to other test modalities (Table 1). Among these, DE was associated with significantly better predictive performance than dipyridamole perfusion imaging. Ambulatory electrocardiography, exercise electrocardiography and radionuclide ventriculography yielded lower sensitivity, reasonable specificity with no significant difference in predictive performance (Table 1). When using summary receiver characteristic analysis to compared the prognostic accuracy of these tests, the results showed that DE had a significantly better discriminatory power than the other tests.

3. Cardiac risk reduction strategies

Risk reduction strategies aimed at reducing the incidence of perioperative cardiac complications can be grouped into three categories: (1) preoperative medical therapy, (2) preoperative coronary revascularization, and (3) intraoperative and postoperative monitoring.

3.1. Preoperative medical therapy

Beta-blockers

The ability of beta-blockers to reduce the perioperative incidence of death from cardiac causes and nonfatal myocardial infarction has been widely studied. The first randomised, controlled study evaluating the cardioprotective effect of beta-adrenergic antagonists in patients undergoing major surgery was performed by Mangano et al [24]. In this study, 200 high-risk patients who had or were at risk for CAD were randomly assigned to receive atenolol or placebo during the perioperative period. Atenolol was administered intravenously or orally beginning two days preoperatively and continuing for seven days postoperatively. The patients were monitored perioperatively for cardiac events and then followed for two years after surgery. There was no difference in the incidence of perioperative myocardial infarction or death from cardiac causes. During the two-year follow-up period, the mortality was 10% in patients given previously atenolol and 21% in the controls. The failure of atenolol to significantly alter the perioperative outcome may be related to the low incidence of serious perioperative cardiac events in the study population (3%). The study included both patients with known CAD and those with only coronary risk factors, and patients underwent various surgical procedures. Finally, the difference in long-term cardiac events may be related to the unequal distribution of cardiac risk factors in the two groups. Patients previously treated with atenolol had more high-risk factors than the placebo group.

In contrast, the study of Poldermans et al. studied the perioperative use of bisoprolol in elective major vascular surgery [25]. Bisoprolol was started on average thirty days preoperatively with dose adjustment to achieve a resting heart rate of no more than 60 beats per minute, and continued for 30 days postoperatively. The study was confined to a population of patients who were identified by clinical screening and DE as being at high risk. Patients with extensive regional wall-motion abnormalities were excluded. The overall incidence of the combined end point of death from cardiac causes or nonfatal myocardial infarction was reduced tenfold from 34% in the standard-care group to 3.4% in the bisoprolol group (Figure 2).

Alpha2-Adrenergic Agonists

The effect of alpha2-adrenergic agonists has also been studied in the perioperative period. Randomised studies comparing clonidine with placebo failed to demonstrate that clonidine reduced the rates of myocardial infarction and death from cardiac causes [26, 27]. Mivazerol, an intravenous alpha2-adrenergic agonists was compared with placebo in a cohort of 2801 patients who were known to have coronary disease or risk factors for it and who underwent major vascular or orthopaedic procedures [28]. In the group of patients with known coronary artery disease who underwent major vascular surgery, mivazerol was associated with a significantly lower incidence of myocardial infarction and death from cardiac causes.

Other agents

The prophylactic use of other agents such as nirtoglycerin or diltiazem have been studied for the prevention of cardiac complications [29, 30]. However, these studies were too small to have the power to detect differences in the incidence of cardiac events.

New agents

The effect of proton pump inhibitors is currently undergoing clinical evaluation. These drugs are potent inhibitors of the Na/H exchanger type 1 (NHE-1). Inhibition of the NHE-1represents an attractive approach for reducing perioperative myocardial ischemic injury [31]. The mechanism of action and available animal data suggest that NHE-1 inhibitors reduce the structural and functional consequences of myocardial ischemia. These pharmacological effects may result in significant clinical benefits by preventing or attenuating the consequences of myocardial ischemic events in the perioperative setting.

3.2. Preoperative coronary revascularization

3.2.1 Percutaneous Revascularization

Preoperative evaluation may occasionally identify a patient who would benefit from coronary revascularization. Percutaneous transluminal coronary angioplasty (PTCA), primarily the use of a balloon, has been studied in patients who were undergoing noncardiac surgery [32-34]. The indication for PTCA most likely included the need to relieve symptomatic angina or to reduce the perioperative risk of ischemia identified by non-invasive testing. The incidence of perioperative cardiac death and nonfatal myocardial infarction was low in all three cohorts, but no comparison group were included. In a more recent study Posner and colleagues [35] compared adverse cardiac outcomes after noncardiac surgery among patients with prior PTCA, patients with nonrevascularized CAD, and normal controls. The results of the study showed that patients revascularized by PTCA >90 days before noncardiac surgery had a lower risk of poor outcome than those patients revascularized less than 90 days. These findings and the only modest correlation between the location of the culprit coronary lesion assessed preoperative by DE and the perioperative MI suggest that prophylactic use of PTCA should not be used solely as a means of reducing perioperative cardiac risk.

Patient recently treated with PTCA and coronary stenting are at high-risk for coronary thrombosis and bleeding. Kaluza and colleagues studied 40 patients who underwent coronary stent placement less than six weeks before surgery [36]. There were seven myocardial infarction, 11 major bleeding episodes and eight deaths. All deaths and myocardial infarctions, as well as 8 of 11 bleeding episodes, occurred in patients subjected to surgery within 14 days from stenting. The main predictor of outcome was the time between stenting and surgery, and stent thrombosis accounted for most of the fatal events. The cause for stent thrombosis was interruption of antiplatelet drugs one or two days before surgery, whereas serious bleeding complications occurred due to postprocedural anticoagulant therapy. These results suggest that elective noncardiac surgery should be postponed for several weeks after coronary stenting, allowing the completion of currently recommended 2-6 weeks antiplatelet therapy.

3.2.2 Coronary artery bypass grafting

The effectiveness of coronary artery bypass grafting (CABG) to reduce the incidence of perioperative cardiac complications has not been addressed by randomised trials. A retrospective review by Eagle and colleagues is the largest study to date that supports the protective effect of CABG prior to noncardiac surgery [37]. In this study 3368 Coronary Artery Surgery Study (CASS) registry enrolees were either treated with CABG or medical therapy. The authors found that prior CABG was most protective in patients with advanced angina and/ or multivessel CAD. A 50 % reduction (3.3% vs. 1.7%) was noted in the group of patients who had undergone CABG than in those who received medical therapy. Though this study suggests a protective effect of prior CABG but the type of analysis did not take into account the cumulative risk of both coronary and peripheral revascularization.

A more recent study on Medicare beneficiaries showed that preoperative revascularization significantly reduced the one-year mortality rate for patients undergoing aortic surgery but had no effect on the mortality rate for those undergoing infrainguinal surgery [38]. These findings support the hypothesis that, when bypass surgery indicated may reduce the risk of cardiac complications.

Finally, in the Bypass Angioplasty Revascularization Investigation trial coronary angioplasty was compared with CABG in 501 patients undergoing noncardiac surgery. The study provided evidence that rates of cardiac death and myocardial infarction were similarly low after CABG or coronary angioplasty in patients with multivessel disease [39].

4. Intraoperative and postoperative monitoring

4.1. Transesophageal echocardiography and 12-lead electrocardiography

Intraoperative monitoring for myocardial ischemia has been advocated to identify patients at high risk for perioperative ischemic outcomes associated with noncardiac surgery [40]. However, conventional intraoperative monitoring techniques are relatively insensitive for myocardial ischemia. Therefore, there has been more reliance on sophisticated techniques like transesophageal echocardiography (TEE) and 12-lead electrocardiography (ECG). Eisenberg and colleagues compared the routine monitoring for myocardial ischemia with TEE or 12-lead ECG during noncardiac surgery with clinical data and intraoperative monitoring using two-lead ECG. They concluded that TEE and 12-lead ECG had little incremental clinical value in identifying patients at high risk for perioperative ischemic outcomes [41]. The limitation of this study was that patients were under close hemodynamic control and the study was performed in a selected group of patients.

4.2. Pulmonary-artery catheter and central venous catheter

Isaacson and colleagues studied the utility of a pulmonary-artery catheter or a central venous catheter for perioperative monitoring in patients undergoing abdominal aortic reconstructive surgery [42]. No statistically significant difference occurred between the two groups with regard to morbidity (perioperative cardiac, pulmonary or renal sequel), mortality rate, and duration of intensive care, postoperative hospital stay, or cost of hospitalisation. The authors concluded that the choice of central venous catheter or pulmonary artery catheter monitoring makes little difference in outcome after abdominal aortic surgery. In a later randomised clinical trial the routine use of pulmonary artery catheters and hemodynamic optimisation was studied in patients undergoing aortic surgery. The authors observed a higher number of cardiac and renal complications in the pulmonary artery catheter group compared with the standard group. The results of the study showed that the utility of pulmonary artery catheters during aortic surgery was not beneficial and may be associated with a higher rate of intraoperative complications. Recently, Pronovost and colleagues studied the role of organization characteristics of intensive care units to outcomes of abdominal aortic surgery [43]. Their findings suggest that having daily rounds by an ICU physician leads to 3-fold decrease in in-hospital mortality, and cardiac arrest. Therefore, this is the only approach to monitoring for which there is evidence showing that it improves the outcome in patients who are undergoing major vascular surgery.

5. Diagnosis of postoperative cardiac complications

In the perioperative period coronary symptoms may be masked due to sedatives and analgesic drugs. The presence or absence of myocardial damage can be assessed objectively by number of different means, including (1) measurement of myocardial proteins in the blood, (2) electrocardiography recordings (ST-T segment wave changes, Q waves), (3) imaging modalities such as myocardial perfusion imaging, echocardiography and contrast ventriculography [44].

5.1. Biochemical markers of myocardial injury necrosis

Myocardial injury and necrosis can be diagnosed by the appearance of different proteins released from the damaged myocytes into the circulation. Myoglobin, cardiac troponins I and T, creatinine kinase, creatinine kinase MB fraction, lactate dehydrogenase are the most commonly used biomarkers to detect injury and necrosis [44].

The cardiac troponins have emerged as sensitive and specific, and preferred biomarkers to detect myocardial injury and infarction [45]. Cardiac troponin I or T can be useful for a diagnosis of myocardial infarction since this is not normally detectable in the blood of healthy individuals but increases after myocardial infarction to levels over 20 times higher than the cut-off value (usually set only slightly above the noise level of the assay). Cardiac troponins are particularly valuable when there is clinical suspicion of either skeletal muscle injury (which is often occurs during surgical opening of the abdomen) or a small myocardial infarction that may be below the detection limit for CK and CK-MB measurements. Levels of cardiac troponins may remain elevated for up to 10 to 14 days. This allows making what has been termed the retrospective diagnosis of acute myocardial infarction.

If cardiac troponin assays are not available, the best alternative is CK-MB [44]. However, CK-MB is less tissue-specific than cardiac troponin. As with cardiac troponin, an increased CK-MB value is defined as one that exceeds the 99^th percentile of CK-MB values in a reference control group. To diagnose myocardial infarction elevated values for biomarkers should be recorded from two successive blood samples. Measurement of total CK is not recommended for the routine diagnosis of myocardial infarction, because of the wide tissue distribution of this enzyme [44].

5.2. Electrocardiography

The ECG may show signs of myocardial ischemia, such as ST segment and T wave changes, signs of myocardial necrosis, specifically changes in the QRS pattern. Myocardial ischemia or necrosis may be defined from standard 12-lead ECG criteria in the absence of specific QRS changes (e.g. bundle branch block, left ventricular hypertrophy, Wolf-Parkinson-White syndrome). However, not all patients who develop myocardial necrosis exhibit ECG changes. Therefore, a combination of sensitive biochemical markers and 12-lead ECG should be used for the verification of myocardial ischemia or necrosis.

5.3. Imaging

There are three routinely used conventional methods that have been used for ruling out or verifying the presence of myocardial infarction or ischemia. These are cross-sectional echocardiography, radionuclide angiography and SPECT perfusion imaging [44].

The advantages of echocardiography is that allows assessment of most nonischemic causes of acute chest pain, such as pericarditis, valvular heart disease, pulmonary embolism and pathologic problems of the aorta [46].

Radionuclide techniques enable to assess myocardial perfusion and function at the time of clinical symptoms. The advantage of these techniques is that they allow quantitative analysis. The accuracy of the technique is high when interpreted by skilled observers [47].

Nevertheless, biomarkers are more sensitive, more specific and less costly for the diagnosis of myocardial necrosis. For instance, injury involving at least 20% of myocardial wall thickness is necessary to enable the physician to detect a segmental wall motion abnormality with echocardiography. In case of radionuclide techniques more than 10 g of myocardial tissue must be injured before a radionuclide perfusion defect can be resolved [44].

6. Conclusions

1) Patients undergoing infrarenal aortic surgery without cardiac risk factors represent a low risk population. Additional evaluation for CAD is not recommended, beta-blockers reduce both perioperative and late cardiac events.

2) Patients with one or more risk factors represent an intermediate to high-risk population. Additional evaluation for CAD is recommended according to the present guidelines. Both nuclear tests and stress echocardiography can identify patients at risk for perioperative and late cardiac events. Beta-blockers should be prescribed to all patients, coronary revascularization should be limited only to patients who have a clearly defined need for revascularization independent of the need for surgery.

3) Preoperative cardiac evaluation of patients undergoing major vascular surgery offers the possibility to the treating physicians to reduce cardiac risk by treating myocardial ischemia, hypertension, and hyperlipidemia. This will reduce perioperative risk and improve long-term outcome.

7. References

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Figure 1. Incidence of perioperative cardiac death and myocardial infarction in vascular surgery over time

N=754

N=3508

N=2265

N=1789

N=218

Figure 2. Kaplan-Meier Estimates of the Cumulative Percentages of Patients Who Died of Cardiac Causes or Had a Nonfatal Myocardial Infarction during the Perioperative Period. Bars indicate standard errors. The difference between groups was significant (P<0.001 by the log-rank test) [25].

	Standard care

Bisoprolol

P<0.001

No. at risk

Standard care

53 38 37 37 35

Bisoprolol

59 58 57 57 57

Table 1. Meta-analysis Sensitivity and Specificity of Preoperative Tests for Perioperative Cardiac Death and Nonfatal Myocardial Infarction in Patients Undergoing Elective Major Vascular Surgery* [23]

Noninvasive test†	No. patients	Sensitivity (%; 95% CI)	Specificity (%; 95% CI)
A-ECG	893	52 (21-84)	70 (57-83)
Ex-ECG	685	74 (60-88)	69 (60-78)
RNV	532	50 (32-69)	91 (87-96)
DTS	3,354	83 (77-89)	49 (41-57)
DiSE	850	74 (53-94)	86 (80-93)
DSE	1,877	85 (74-97)	70 (62-79)

*CI indicates confidence interval

†Tests are sorted according to ascending sensitivities; A-ECG, ambulatory electrocardiography; DTS, dipyridamole thallium scanning; Ex-ECG, exercise electrocardiography; DSE, dobutamine stress echocardiography; RNV, radionuclide ventriculography; DiSE, dipyridamole stress echocardiography;