Perioperative Cardiac Risk Stratification for Noncardiac Surgery

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1 REVIEW ARTICLE Perioperative Cardiac Risk Stratification for Noncardiac Surgery Part 2 in a Series on Preoperative Risk Assessment Gerhard Bauriedel, Dirk Skowasch, Berndt Lüderitz SUMMARY Introduction: Cardiovascular complications arising from noncardiac surgery contribute substantially to perioperative morbidity and mortality. Methods: Review of relevant literature; clinical experience. Results: The basic tools for preoperative risk assessment are the evaluation of specific risk factors, of the patient s functional capacity, and of procedure specific risks. Additional non-invasive tests have low predictive value for risk stratification. Preoperative coronary revascularization is seldom beneficial. Patients at low or intermediate perioperative risk should therefore not undergo complex examinations or interventions, which entail unnecessary delay and increased costs. Patients at high risk should be evaluated by stress testing or dobutamine stress echocardiography and possibly by invasive strategies, as individually indicated. The indication for revascularization relates to preexisting symptoms and disease, and must be assessed independently of surgery. Beta-blockers and statins have recently been shown to decrease perioperative ischemia and should be administered where there is significant cardiovascular risk. Discussion: This review presents an algorithm for the management of patients undergoing noncardiac surgery. Continuing to improve perioperative strategies remains a pivotal interdisciplinary task and should be undertaken with respect to existing evidence and clinical guidelines. Dtsch Arztebl 2007; 104(22): A Key words: noncardiac operation, perioperative risk stratification, coronary artery disease, revascularization, beta-blocker W ith an incidence of 2%, cardiovascular complications during noncardiac surgery are an important cause of perioperative morbidity and mortality (1 4). Indeed, in high risk patients such as those undergoing vascular surgery, myocardial infarction (MI) has a reported incidence as high as 34% and is associated with substantial morbidity, longer hospital stays, and mortality rates ranging from 25% to 40% (2, 5, e1). Older patients, who frequently have coronary artery disease (CAD) and chronic heart failure (CHF) (6), are at particular risk and also represent the largest proportion of patients undergoing surgery (e2 e4). The goal of pre- and perioperative risk assessment and stratification is therefore to reduce perioperative mortality, morbidity, and associated hospital days and hospital costs. Until recently, emphasis was placed on patient- and procedure-specific risks. However, a paradigm shift can be observed in recent studies, which aim to modify risks by better understanding the causes of perioperative ischemia and developing targeted prevention strategies. The present review is based on relevant literature and the authors' clinical and research experience with this topic. It approaches the subject from the perspective of a cardiologist and develops an algorithm for the management of patients undergoing noncardiac surgery. Clinical predictors Patient-specific risk factors Amedical history and physical examination are key to identifying cardiac risks and performing a preliminary perioperative risk stratification. High-risk cardiac conditions include unstable or severe angina, MI within the past six weeks, decompensated heart failure, symptomatic valvular heart disease, and malignant arrhythmias. Medizinische Klinik I Klinikum Meinigen: Prof. Dr. med. Bauriedel; Medizinische Klinik und Poliklinik II Universitätsklinikum Bonn: Prof. Dr. med. Bauriedel; PD Dr. med. Skowasch; Prof. Dr. med. Dr. h. c. Lüderitz Dtsch Arztebl 2007; 104(22): A

2 TABLE 1 Clinical predictors of increased perioperative cardiac risk (3, 7) High risk Intermediate Risk Low Risk Myocardial infarction, bypass surgery, Myocardial infarction >6 weeks Myocardial infarction >3 months, PCI <6 weeks, acute <3 months, bypass surgery, PCI >6 weeks asymptomatic without therapy, coronary syndrome <3 months or >6 years or bypass surgery, PCI >3 months with antianginal therapy <6 years, asymptomatic, without antianginal therapy Severe angina pectoris Mild angina pectoris Family history of CAD (CCS grade III or IV) (CCS grade I or II) hypercholesterolemia, smoking Decompensated Compensated heart failure Arterial hypertension heart failure Ejection fraction <35% History of stroke Severe arrhythmias Diabetes mellitus Arrhythmias*, Abnormal ECG* Severe valvular disease Renal insufficiency Advanced age CCS, Canadian Cardiovascular Society; CAD, coronary artery disease; PCI, percutaneous coronary intervention; * Arrhythmias such as atrial fibrillation, supraventricular arrhythmias, ECG abnormalities such as bundle-branch block patterns, ST-T abnormalities, left ventricular hypertrophy Comorbidities such as diabetes mellitus, stroke, renal insufficiency, and pulmonary disease also affect the perioperative course (7). A consensus paper published by the two major American cardiology societies groups the most important patient-related risk factors into three stratified risk categories (table 1). Functional capacity Functional capacity is an important measure of perioperative risk. The term refers to an individual's ability to perform normal daily activities, such as stair climbing, household chores, and regular exercise, which correlate well with maximum oxygen consumption during bicycle ergometer exercise (8, e5 e6). Impaired functional capacity is associated with poorer short- and long-term outcomes in patients undergoing noncardiac surgical procedures. Patients in whom ischemia is induced by low-level ergometer exercise (heart rate <100/min) represent a high-risk group, whereas patients with good exercise tolerance (heart rate >130/min) without ischemia represent a low-risk group. Vascular patients who are able to reach 85% of their maximum heart rate during exercise have a low risk of a perioperative cardiac events. In contrast, the inability to climb two flights of stairs is associated with a positive predictive value of 89% for cardiopulmonary complications (9, e1). Surgery-specific risk Surgery-specific risk is related to the type of surgery planned and the degree of hemodynamic stress associated with the procedure. In this regard, the duration and intensity of coronary and myocardial stressors play a crucial role in the development of perioperative cardiac events, especially during emergency surgery. The surgery-specific risk for noncardiac procedures can be divided into three categories (table 2). Risk stratification scoring systems Over the past 30 years, a number of multivariate scoring systems have been developed to aid in preoperative cardiac risk stratification (1 2, 9 10). One of the first of these scoring systems, the Goldman index, included nine weighted, independent variables with which it was able to distinguish reliably between high- and low-risk categories (1). Lee et al (2) developed a simplified cardiac risk index based on six independent predictors without relative weights (table 3). According to their findings, the risk of cardiac events such as MI, pulmonary edema, ventricular fibrillation, and severe bradycardia when 0, 1, 2, or 3 of these risk predictors were present was 0.4%, 0.9%, 7%, and 11%, respectively (2). Thus, a suitable instrument is available for stratifying patients with intermediate risk factors more precisely (3). Dtsch Arztebl 2007; 104(22): A

3 Preoperative testing Non-invasive preoperative testing Once patient-specific risk factors, functional capacity, and surgery-specific risks have been assessed, the need for additional non-invasive tests must be established. These should be considered if they can be expected to provide additional information to aid in risk stratification. However, if clinical evaluation, functional capacity, and type of surgery indicate that a patient is at low risk, further tests are rarely needed. The guidelines published by the two major American cardiology societies do not recommend ECG monitoring or evaluations of left ventricular pump function in asymptomatic patients undergoing low-risk surgery (3). However, in clinically intermediate- or high-risk patients scheduled for larger procedures, a preoperative ECG is recommended in the event of recent chest pain or ischemic equivalent. Echocardiographic measurement of ejection fraction is recommended in patients with current or prior heart failure, valvular heart disease, or pulmonary hypertension (3, e7). Testing for ischemia is often limited by poor exercise tolerance, the interference of ECG abnormalities, or the low positive predictive value of these abnormalities, which ranges from 4% to 38% for perioperative complications. In contrast, non-invasive stress tests have been shown to have an excellent negative predictive value of 90% to 100% (3, 7). Normal findings on these tests are very useful because they allow physicians to correct risk estimates that were initially too high. In a prospective trial, additional evaluation with myocardial scintigraphy was not superior to clinical risk stratification alone; indeed, manifest CAD and age greater than 65 years were better predictors of cardiac complications (11). In another study, dobutamine stress echocardiography was able to show that the likelihood of experiencing later cardiac complications was five times higher in patients with 3 or more clinical risk factors and with stress-induced myocardial ischemia, even in those receiving effective beta-blocker treatment (12). In these patients, invasive coronary testing is advisable. Preoperative exercise or pharmacological stress testing is beneficial, in particular, to patients with intermediate clinical predictors (table 1) or with low functional capacity who are undergoing a larger surgical procedure or vascular surgery (3). Invasive preoperative testing Coronary angiography is associated with a mortality of 0.01% to 0.05% and a morbidity of 0.03% to 0.25% (e8). The indications for preoperative coronary angiography are mostly independent of surgery and are similar to those identified for the nonoperative setting. Indications for coronary angiography include evidence of a high risk of adverse outcome based on non-invasive test results, angina unresponsive to medical therapy, acute coronary syndrome, or equivocal non-invasive test results in patients undergoing high-risk surgery (3). Strategies for reducing perioperative risk Examples of strategies for lowering perioperative risks include the choice of anesthesia technique, perioperative therapy with beta-blockers and other drugs, and reducing blood loss/anemia and postoperative pain (e1). Patients on antihypertensive treatment should continue taking their medication up to the time of surgery and resume it as soon as possible following the procedure. Surgery should be delayed if blood pressure remains persistently above 180/110 mmhg (e9). The indications for antiarrhythmic therapy, including if necessary the additional implantation of pacemakers or implantable cardioverter defibrillators (ICD), must be assessed independently of surgery (13, e10). Perioperative monitoring using 12-lead electrocardiography, transesophageal echocardiography (e3, e11), and pulmonary artery catheterization (e12) showed no benefits. When weighing risks, it may be advisable to limit the scope of the procedure or choose a staged surgical approach. Revascularization strategies for coronary artery disease Percutaneous coronary intervention/stent placement Findings of ischemia or CAD during non-invasive testing lead to coronary catheterization and potentially to treatment of the associated plaques by percutaneous coronary intervention (PCI). Currently there are no data to suggest that preoperative PCI is beneficial in reducing perioperative risks (3, 14 15, e1). In patients at high clinical risk and with moderate to severe reversible ischemia, coronary revascularization with PCI prior to the planned Dtsch Arztebl 2007; 104(22): A

4 TABLE 2 Surgery-specific cardiac risks (3, 7, 9, 19) High risk (frequency >5%) Intermediate risk (frequency <5%) Low risk (frequency <1%) Major emergency operations, Intraperitoneal, intrathoracic, Endoscopic and superficial especially in older patients and orthopedic surgery procedures Prolonged surgical procedures Head and neck surgery Plastic and reconstructive with large fluid shifts and/or blood loss Brain surgery surgery Aortic and other major vascular surgery; Carotid endarterectomy Breast surgery peripheral vascular surgery Prostate surgery Cataract surgery Cardiac risk in terms of cardiac death and nonfatal myocardial infarction vascular procedure was associated with an improved 5-year survival rate, but conferred no benefit at 30 days or 1 year (14). These findings were confirmed by a multicenter study including patients with clinically significant but stable CAD; most subjects had 1 or 2 vessels amenable to coronary revascularization. Exclusion criteria were left stem stenosis, severe valvular aortic stenosis, or severe left ventricular dysfunction with an ejection fraction less than 20%. These recent findings show once again that preoperative PCI is not beneficial in patients with stable CAD, sufficient pharmacological therapy, and low surgical risk (15). The indications for performing PCI prior to noncardiac surgery are thus similar to those identified for the use of PCI in general, e.g. in cases of acute coronary syndrome or angina unresponsive to medical therapy (3, 12, 16, e13). The placement of coronary stents prior to surgery is associated with the risk of stent thrombosis and perioperative bleeding during the postsurgical period (9, e14). After implantation of a coronary stent, dual antiplatelet therapy with aspirin and clopidogrel is obligatory. For uncoated stents, the combination of aspirin and clopidogrel must be administered for 4 weeks after stent placement; premature interruption of therapy substantially increases the risk of life-threatening thrombosis of the target coronary vessel (17, e14). As a result, elective surgical procedures should be postponed until 4 weeks of therapy have been completed (17, 18, e14, e30). In the case of drug-eluting stents that release sirolimus, paclitaxel, or other antiproliferative agents, dual antiplatelet therapy must be continued for a considerably longer period of time. At present, the American cardiology societies recommend a duration of 12 months (e30); however, no randomized, prospective studies on the optimal duration of therapy in this context have been conducted to date. Following guidelines published by the European Society of Cardiology, the German Society of Cardiology recommends administering clopidogrel as adjunctive medication for 6 to 12 months after placement of drug-eluting stents, based on the patient's individual risk of stent thrombosis (18). Drug-eluting stents should not be used if surgery is to be performed during the following 12 months. In such a case, it is advisable to perform angioplasty alone and, if necessary, to implant an uncoated stent (18, e30). However, if a drug-eluting stent was implanted and a patient needs surgery that requires the premature TABLE 3 Risk Factors for Perioperative Cardiac Complications and Indications for Perioperative Administration of Beta-Blockers or Statins (2, 8-10) Risk factors Odds ratio (95% CI) Indication for Beta-blocker Impaired functional capacity 1,8 (0,9 3,5) (+) (+) Heart failure 1,9 (1,1 3,5) + (+) CAD/ischemic heart disease 2,4 (1,3 4,2) + + High-risk intervention 2,8 (1,6 4,9) + + Diabetes mellitus 3,0 (1,3 7,1) + + Renal failure 3,0 (1,4 6,8) (+) (+) Statin CI, confidence interval; (+), if related to vascular causes, heart failure, or diabetes Dtsch Arztebl 2007; 104(22): A

5 interruption of clopidogrel therapy, the patient should, if feasible, continue taking aspirin and resume clopidogrel as soon as possible so as to avoid late stent thrombosis (e30). Operative coronary revascularization The indications for prophylactic coronary artery bypass surgery (CABS) before noncardiac surgery are identical to those for elective CABS alone (3). Examples include left stem stenosis and multivessel CAD, often in conjunction with proximal left anterior descending artery stenosis, refractory coronary ischemia, or left ventricular dysfunction. The 10-year data from the Coronary Artery Surgery Study (CASS) database show that prior CABS was associated with lower postoperative mortality (1.7% versus 3.3%) and a lower MI rate (0.8% versus 2.7%) compared to pharmacological therapy alone. These differences were only observed in patients undergoing higher-risk surgery. In contrast, patients undergoing urological, orthopedic, or superficial operations had a mortality of less than 1%, regardless of prior coronary treatment. For asymptomatic patients who have had CABS within the past 5 years, further cardiac testing before noncardiac surgery is generally not recommended (3). Combined with the risk of delaying the necessary noncardiac operation, the risk of CABS usually offsets that of prompt surgery (20, e1). For example, data from the CASS registry (20) show that in patients with stable angina, the cumulative mortality for CABS (1.4%) and the planned noncardiac procedure (0.9%) was similar to that observed in patients who had not undergone prior revascularization (2.4%). In fact, there is some indication that patients who undergo prophylactic CABS are even at increased risk (e1). Pharmacological strategies Beta-blockers A number of studies have shown that beta-blockers significantly reduce perioperative cardiac complications. In a randomized, placebo-controlled trial in patients with known CAD or risk factors for arteriosclerosis, there were no perioperative deaths in the atenolol group, whereas perioperative mortality in the placebo group was 1%. After 6 months, there were still no deaths among patients on beta-blocker therapy, but mortality in the placebo group had risen to 8% (21). Clear differences between the two groups could still be observed DIAGRAM Algorithm for managing patients undergoing noncardiac surgery. ACBS, aortocoronary bypass surgery; CCS, Canadian Cardiovascular Society; DSE, dobutamine stress echocardiography; nwma, new wall motion abnormalities, PCI, percutaneous coronary intervention; RF, risk factor(s) according to the revised cardiac risk index (2), as shown in table 3 Dtsch Arztebl 2007; 104(22): A

6 1 year and 2 years later (10% versus 21%). The lower mortality in the beta-blocker group was primarily due to a reduction in deaths from cardiac causes during the first 6 to 8 months after surgery (21). A study of patients undergoing abdominal aortic surgery or infrainguinal procedures was stopped early after bisoprolol showed an impressive reduction in perioperative mortality (17% versus 3%) and MI (17% versus 0%) (5). In total, 83% of patients had a low or intermediate risk of perioperative cardiac complications (0 to 2 risk factors). In this subgroup, less than 1% of patients receiving beta-blocker therapy experienced cardiac complications, regardless of their DSE results (12). In contrast, DSE provided additional prognostic information for patients with 3 or more risk factors: among patients receiving beta-blockers, those without stress-induced ischemia showed an incidence rate of 2% compared to 11% in those with stress-induced ischemia. In summary, beta-blockers reduce the incidence of perioperative cardiac complications in clinically intermediate- and high-risk patients (table 3). However, the available evidence for the effectiveness of beta-blockers in no-risk or low-risk patients is inconclusive (13, 22 23, e16 e18). Current recommendations suggest that patients in whom long-term betablocker therapy is indicated should start a beta-blocker immediately before the noncardiac procedure and continue treatment until 7 days (preferably 30 days) after surgery. The ideal dose remains unclear, and it is unknown whether the benefits observed in studies to date represent a class effect for all beta-blockers. For patients with an indication for long-term beta-blocker treatment, however, beta-blockers should be started days or weeks before the elective surgery, with the dose titrated to achieve a heart rate of 50 to 60 beats per minute (3, 9). Data from DECREASE-IV (fluvastatin and bisoprolol) and POISE (metoprolol) should help to shed more light on the role of beta-blockers in low- to intermediate-risk patients (e18). Statins A number of studies, including randomized trials, have shown that statin treatment is associated with lower perioperative mortality (24, e19 e23). In a multicenter observational study of more than patients who underwent noncardiac surgery, treatment with lipid-lowering therapy for the most part with statins within the first 2 hospital days was associated with a lower risk of mortality (2.1% versus 3.1%) (e23). Further randomized clinical trials are needed to confirm these observations and determine the optimal duration and dose of statin treatment. A look at the important cardiovascular risk factors listed in table 3 shows that statins are also indicated frequently in patients who are not undergoing surgery. In general, all patients with arteriosclerotic vascular disease should receive long-term statin treatment, as described in the Heart Protection Study (e24); these patients may also experience additional benefits from statin therapy during the perioperative period (e25). Aspirin A recent systematic review based on 10 randomized and 38 observational studies with more than patients demonstrated that preoperative aspirin withdrawal was associated with acute cardiovascular syndromes that developed over the next 9 to 26 days in up to 10% of patients. Although aspirin therapy increased the rate of bleeding complications by a factor of 1.5, it did not increase the severity of these complications, except in patients undergoing intracranial surgery or transurethral prostatectomy (25). Based on similar observations in patients with prior acute coronary syndrome (e26, e30), established aspirin therapy should generally be continued perioperatively. Randomized studies are urgently needed to evaluate the trade-offs between a reduced risk of MI and increased risk of bleeding. Alpha-2 adrenoceptor agonists Alpha-2 adrenoceptor agonists improve cardiovascular morbidity and mortality in noncardiac and cardiac surgery (e27). In a prospective, randomized trial studying patients undergoing noncardiac surgery, prophylactic clonidine administration (0.2 mg orally) reduced perioperative myocardial ischemia, as well as mortality at 1 month and 2 years, without affecting the rate of MI (e28). Currently, no data are available on concomitant treatment with alpha-2 receptor agonists in patients on beta-blocker or statin therapy. Due to the considerably Dtsch Arztebl 2007; 104(22): A

7 larger body of evidence supporting the use of beta-blockers, especially for certain subgroups of patients, beta-blockers should remain the medication of choice. Alpha-2 adrenoceptor agonists can potentially be regarded as an alternative regimen. From risk stratification to risk modification The goal of preoperative risk assessment is to ensure optimal perioperative care and thus reduce the incidence of cardiac complications. To reach this goal, the physician must determine the balance of risks and benefits on an individual basis, taking into account patient-specific (table 1) and surgery-specific (table 2) risk factors, and, if necessary, the results of preoperative non-invasive/invasive tests. Having a plausible algorithm for risk stratification (diagram) is attractive because it allows physicians to identify and manage acute cardiac problems such as unstable angina, recent MI, decompensated heart failure, severe arrhythmias, or valvular defects prior to surgery and with simple medical treatment (4, 6, 9, e7, e15, e29). This approach is advisable in patients undergoing elective surgery; emergency surgery, however, requires a special assessment of risks. The risks and consequences of not performing surgery should also be considered. However, there is no justification for avoiding surgery in patients with an immediately life-threatening condition such as an impending aneurysm rupture, a rapidly growing tumor, disabling bone fractures, or infections requiring surgical debridement. All other patients have risk factors such as (stable) CAD or other specific components of the revised cardiac risk index (table 3). As the algorithm in the diagram shows, patients at low or intermediate risk should be treated with beta-blockers and, if necessary, statins during the perioperative period. In contrast, patients who have 3 or more risk factors and are undergoing elective surgery should be evaluated for ischemia (e.g. with DSE) and, depending on the results, undergo additional invasive testing (similar risk to that seen in patients with acute coronary syndrome); these high-risk patients should also receive perioperative pharmacological treatment. Finally, in patients with no risk factors, further preoperative testing is unnecessary. Conclusions Continuing to improve perioperative strategies remains a pivotal interdisciplinary task and requires taking existing evidence and clinical guidelines into account. However, although the recommendations made by medical associations provide some guidance on how to perform preoperative testing and risk stratification, a careful clinical evaluation of each patient remains crucial and should always serve as the basis for standardized procedures. Conflict of Interest Statement The authors declare that no conflict of interest exists according to the Guidelines of the International Committee of Medical Journal Editors. Manuscript received on 7 April 2006, final version accepted on 29 May Translated from the original German by Matthew D. Gaskins. REFERENCES For e-references please refer to the additional references listed below. 1. Goldman L, Daldera DL, Nussbaum SR et al.: Multifactorial index of cardiac risk in noncardiac surgical procedures. N Engl J Med 1977; 297: Lee TH, Marcantonio ER, Mangione CM et al.: Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation 1999; 100: Eagle KA, Berger PB, Calkins H et al.: ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to update the 1996 guidelines on perioperative cardiovascular evaluation for noncardiac surgery). Circulation 2002; 350: Karthikeyan G, Bhargava B: Managing patients undergoing non-cardiac surgery: need to shift emphasis from risk stratification to risk modification. Heart 2006; 92: Poldermans D, Boersma E, Bax JJ et al.: The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med 1999; 341: Bauriedel G, Skowasch D, Lüderitz B: Die chronische Herzinsuffizienz. Dtsch Arztebl 2005; 102(9): A Chassot PG, Delabays A, Spahn DR: Preoperative evaluation of patients with, or at risk of, coronary artery disease undergoing non-cardiac surgery. Br J Anaesth 2002; 89: Dtsch Arztebl 2007; 104(22): A

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