Perioperative cardiac evaluation: novel interventions and clinical challenges.

Abstract: Cardiac complications are one of the most important sources of morbidity and mortality after noncardiac surgery. In this review, we discuss the pathophysiology of postoperative cardiac complications and published risk indices and guidelines that allow an estimation of preoperative risk. Recent evidence has challenged the primary role of perioperative beta blockers as a risk reduction strategy. The highest level of evidence for their use is for patients with coronary artery disease or multiple risk factors undergoing vascular surgery. Beta blockers may provide no benefit or may be potentially harmful for low- and intermediate-risk patients and surgeries. For patients with contraindications to beta blockers, diltiazem and clonidine are alternative agents that reduce cardiac risk. Statins are emerging as another potential strategy to reduce cardiac risk, although the evidence is based primarily on retrospective analyses. Coronary artery revascularization does not reduce cardiac complications after noncardiac surgery among patients with stable coronary artery disease.

Key Words: preoperative evaluation, postoperative complications, intraoperative care, cardiac, beta blockers, coronary artery disease

**********

Over 27 million patients undergo surgery each year with 1 to 3% of these suffering a perioperative myocardial infarction (MI). (1) Multiple studies over the past three decades have established the best methods of identifying patients at risk and the accuracy of diagnostic tests. Most recently, the focus has shifted from stratifying perioperative cardiac risk to applying pharmacologic modalities to reduce perioperative cardiac events. The evolving literature empowers clinicians by providing more prevention options for high-risk patients.

In this review, we will address the pathophysiology of perioperative ischemia, commonly used risk assessment tools, perioperative pharmacologic treatment, and remaining challenges in perioperative cardiac care. In addition to an overview of basic principles of preoperative cardiac evaluation, we discuss recent advances and current challenges.

Pathophysiology

Some perioperative myocardial infarctions result from plaque rupture and thrombosis in areas of significant coronary artery stenosis. Autopsy studies have confirmed this mechanism. (2) However, recent articles have shown that other factors also contribute to perioperative ischemia and infarction. (3) In particular, an association exists between perioperative tachycardia, hypertension, and subsequent MI. One third of patients who sustain a postoperative MI have infarctions in areas without associated critical stenoses. (4,5) Perioperative MIs tend to occur early (on the first postoperative day) and are generally non-Q wave in nature. The clinical presentation is often atypical. In contrast to myocardial infarctions that occur in the nonoperative setting, the majority of perioperative events occur without chest pain. Multiple clinical factors contribute to the risk of postoperative myocardial ischemia, including postoperative anemia, hypothermia, and pain. These may exert negative effects via activation of the sympathetic nervous system, which in turn can cause increased blood pressure, heart rate, contractility, coronary vasomotor tone, and coronary vascular sheer stress. (6) These physiologic changes lead to subendocardial ischemia by increasing myocardial oxygen demand in the face of reduced coronary reserve due to underlying coronary artery disease. Evidence suggests that in addition to plaque rupture, hypoxia, hypotension, anemia, tachycardia, increased coagulability, and increased sympathetic tone all appear to contribute to the pathophysiology of perioperative MI. (6,7)

Clinical Evaluation

Since the development of the Goldman Cardiac Risk Index in 1977, (8) several organizations have published clinical practice guidelines, most notably the American Heart Association/American College of Cardiology (AHA/ACC) which published a guideline for perioperative cardiovascular evaluation for noncardiac surgery in 1996. This guideline has been recently updated in 2002 and offers the most comprehensive approach to preoperative cardiac evaluation for noncardiac surgeries. It focuses clinicians' attention on three major areas: clinical risk predictors, surgery-specific risks, and functional capacity to assure a balanced evaluation.

The guideline stratifies clinical risk predictors into minor, intermediate, or major based on estimated risk of postoperative cardiac events. Minor risk factors are not known to be associated with postoperative cardiac events, while the presence of major risk predictors warrants prompt and aggressive investigation and treatment. (Table 1). (9) The presence of one or more of these clinical predictors will place the patient in the corresponding risk group, thereby guiding the urgency and intensity of the investigation. An alternate clinical risk prediction tool, the Revised Cardiac Risk Index (RCRI), may equally predict risk. (10) It involves the presence or absence of six clinical risk factors (Table 2). Zero, one, two, or three (or more) risk factors are categorized into Class I, II, III, or IV respectively. The corresponding postoperative cardiac complication rates range from less than 1% to over 10%. Since clinical assessment based only on clinical risk predictors is one-dimensional and therefore inadequate, the AHA/ACC guideline also incorporates surgery-specific risks and functional capacity.

The Goldman Cardiac Risk Index first identified the importance of surgery-specific risks. (8) The duration of the procedure, location of the operation, and amount of tissue handling combine to confer different risks associated with various types of surgeries. The AHA/ACC guideline included a more detailed estimate of surgery-specific risks based on postoperative cardiac events for each type of surgery based on the Coronary Artery Surgery Study (CASS) registry. (11) Surgeries were then categorized into low, intermediate, and high-risk surgical groups (Table 3). This adds another dimension to the patient's overall preoperative risk assessment. A patient with minor clinical predictors has an overall low risk except for high risk or urgent/emergent surgeries. Conversely, a patient with major clinical predictors who is in stable condition has an acceptable overall risk if the proposed procedure is a low risk procedure.

The final major component of this evaluation is an assessment of current functional capacity. Functional capacity is a reliable predictor for postoperative cardiac complications. Functional capacity of less than 4 METS of activity confers a 4% risk of postoperative cardiac events, whereas the risk is as low as 0.7% in patients with greater than 4 METS of capacity. (12) This association, however, was not confirmed in the derivation of the RCRI index; a nonsignificant trend existed toward a lower complication rate with higher functional capacity as measured by the Specific Activity Scale Class. (10) Validated tools allow a simplified assessment of functional capacity. The most commonly used tools are the Duke Activity Index and the VA questionnaire. (13,14) Both tools accurately predict metabolic equivalent and can be easily filled out by patients before their encounter with the medical consultant.

Careful consideration of all three aspects, including clinical characteristics, functional capacity, and surgery-specific risk in accordance with the published AHA/ACC guideline, form the basis for informed decision making regarding further diagnostic testing and/or risk reduction interventions.

Risk Reduction Strategies

Beta Blockers

The most studied risk reduction strategy is perioperative beta blockers. These agents exert their effect by decreasing heart rate, arterial blood pressure, and myocardial oxygen consumption. In 1996, Mangano and colleagues published a landmark study. (15) In this randomized controlled trial of 200 patients undergoing various types of elective surgeries, the authors reported an impressive absolute risk reduction of 15% (number needed to treat (NNT) less than 7) in combined cardiac outcome over a two year follow-up with the use of atenolol. Similar findings resulted from another well designed controlled trial in a different surgical population using bisoprolol. (16) In this study of patients undergoing vascular surgery who had a positive dobutamine stress echocardiogram, perioperative bisoprolol conferred an absolute risk reduction in combined cardiac outcome of 30% (NNT of 3). Based on these studies, perioperative beta blockade quickly became the standard of care. However, one recent randomized controlled trial and preliminary data from two others have shed some doubt as to the efficacy of this intervention. The POBBLE trial published in 2005 was a well designed but relatively small study demonstrating no benefit from perioperative metoprolol among 103 patients undergoing infrarenal vascular surgery. (17) The Metoprolol after Vascular Surgery (MaVS) trial also reported no benefit from metoprolol in a trial of 497 patients undergoing vascular surgery. (18) In addition, the DIPOM trial studying the effect of metoprolol in diabetic patients did not show a significant advantage of perioperative use of metoprolol. (19)

More recently, Lindenauer et al conducted a retrospective cohort study using administrative data from over 300 hospitals. Using the schema of the Revised Cardiac Risk Index (RCRI), patients with a score of 0 or 1 (equivalent to minor clinical predictor group) who received perioperative beta blockers unexpectedly had higher in-hospital mortality rates (adjusted OR 1.46, 95% CI 1.36-1.57 and 1.18, 95% CI 1.08-1.29, respectively). In contrast, among patients with RCRI scores of 2 or higher, beta blocker usage was associated with a decrease in in-hospital mortality. (20) Patients with RCRI scores of 2, 3, and 4 had adjusted ORs of 0.95 (95% CI 0.85-1.06), 0.77 (95% CI 0.67-0.88), and 0.62 (95% CI 0.52-0.73) respectively. In a recent rigorous systematic review of the literature, the authors identified a significant risk of symptomatic bradycardia and hypotension with perioperative beta blockade, on the order of a number needed to harm (NNH) of 12 and 50, respectively. (21) These data suggest that judicious use of these agents in carefully selected moderate and high-risk patients assures overall benefit.

Although one may subscribe to the strategy of empiric use of beta blockers without any further noninvasive stress testing, even for high-risk patients, a recent study suggests a benefit to dobutamine stress echocardiography (DSE) in selected patients. In this study, 83% of patients with less than 3 clinical risk factors benefited from beta blockers (0.8% versus 2.3%) independent of DSE results. In the remaining 17% of patients with 3 or more clinical risk factors, residual risk decreased to 2.3% with beta blockers in patients with no or less than 4 segments of wall motion abnormalities on DSE. Among patients with extensive (>5 segments of wall motion abnormality) ischemia on DSE, beta blockers were not beneficial: 33% of patients receiving beta blockers had cardiac events versus 36% of those who did not receive beta blockers. (22) The residual risks were unacceptably high in these very high-risk patients. Thus, noninvasive testing may identify a high-risk subset of patients for whom beta blockers do not reduce risk; therefore, it is inappropriate to forego all noninvasive cardiac testing in high-risk patients.

In the available literature, the duration and timing of the beta blockers vary. Initiation can occur weeks before surgery or only hours before induction of anesthesia. Discontinuation of the beta blocker may occur at discharge or weeks later. What is not variable among study protocols is adherence to an intensive beta blocker titration protocol toward a target heart rate of between 55 to 65. Two preliminary reports that cast doubt on the efficacy of perioperative beta blockade used metoprolol, while two beneficial trials used atenolol and bisoprolol. It is unclear whether differing pharmacological properties may contribute to these different results. A recent Canadian study suggested that atenolol was more efficacious than metoprolol in preventing postoperative MI or death (2.5% versus 3.2%). (23)

A recent update from ACC/AHA regarding perioperative beta blockade concludes that perioperative beta blockers are efficacious for patients at high cardiac risk who are undergoing vascular surgery. (24) There was insufficient evidence to support routine use of these agents for high-risk patients undergoing only low-risk procedures. Clinicians may consider the use of beta blockers for intermediate risk patients undergoing intermediate or high-risk surgeries after a careful consideration of the balance of benefit and risk. Drug choice, dose, duration, and route of use for these agents are highly variable among trials. Further research is needed to fill the remaining gaps in our knowledge base.

Alpha Adrenoceptor Agonists

In recent years, multiple studies have shown a perioperative cardioprotective effect of centrally acting [alpha]-2 agonists. (6,24) The effect is multifactorial and includes a decrease in central sympathetic outflow, dilation of poststenotic coronary arteries and a decrease in peripheral norepinephrine release. (6) For example, in a study of 190 patients undergoing noncardiac surgery, perioperative clonidine significantly reduced the incidence of perioperative myocardial ischemia (31% placebo group versus 14% clonidine group). (25) Likewise, a meta-analysis by Wijeysundera et al showed a decrease in cardiac morbidity and mortality for both noncardiac and cardiac surgeries with the use of three different [alpha]-2 adrenergic agonists (clonidine, mivazerol, and dexmedetomi-dine). Overall, these agents significantly decreased ischemia (RR = 0.76; 95% CI 0.63-0.91) and mortality (RR = 0.64; 95% CI 0.42-0.99). They also reduced myocardial infarction and mortality during vascular surgery (RR = 0.66; 95% CI 0.46-0.94 and RR = 0.47; 95% CI 0.29-0.90 respectively). The route of clonidine administration did not influence risk reduction; topical, oral, and IV administration each appeared to be beneficial. The greatest protective effect was among patients undergoing vascular surgery. (24) Clinicians should consider the use of perioperative clonidine for high-risk patients who have a contraindication to the use of beta blockers. Perioperative clonidine appears to be safe; in the above meta-analysis, there were no statistically significant increases in the incidences of hypotension, CHF, or bradycardia. (24) The available literature does not allow a determination as to whether clonidine is more effective than beta blockers, or if there is an additive beneficial effect.

Statins

Recent research has suggested that use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are associated with fewer perioperative events in vascular surgery patients. The mechanism of action is not fully understood, but may involve inflammatory modulation, modification of endothelial function, decreased inflammation and improved atherosclerotic plaque stability. (26,27) In a case control study of vascular patients, Poldermans et al found that the perioperative mortality among patients using statins was 8% compared with 25% for the control group. (28) The beneficial effect of statins in vascular surgery likely extends to patients undergoing nonvascular surgery, although only one study to date has evaluated patients undergoing nonvascular surgery. In a large retrospective cohort study of 204,885 patients undergoing major noncardiac surgeries, those who received statins within the first two days of hospital admission had an increased survival compared with those who received statins after the second hospital day or not at all. (29) Patients who received lipid-lowering therapy had a lower mortality than those who did not (2.13 versus 3.05%, P < 0.001). The adjusted odds ratio was 0.62 (95% CI 0.58-0.67). The unadjusted OR for mortality in statin users was 0.68 (95% CI 0.64-0.72) compared with nonstatin users (unadjusted OR 0.81 (95% CI 0.70-0.95). Table 4 summarizes the number needed to treat to prevent in-hospital death based on the Revised Cardiac Risk Index.

Although the current literature suggests that perioperative statins significantly decrease perioperative cardiac events, only two of the studies in a recent review of the literature were prospective. (27) Additional randomized trials are needed to confirm the perioperative cardioprotective benefit of statins, to help establish treatment protocols, and to determine perioperative safety. Pending future research, we recommend the following:

* Continue perioperative statins for those patients already on them.

* Initiate statins before surgery in all vascular surgery patients (as much as 30 days preoperatively and at least 2 days preoperatively).

* Use perioperative statins in patients with two or more risk factors as defined by the Revised Cardiac Risk Index.

* Continue the medication indefinitely for patients in whom long-term statin therapy is indicated.

Calcium Channel Blockers 

Although less well studied than beta blockers, calcium channel blockers (CCBs) have also been found to decrease perioperative events, possibly via their negative inotropic, negative chronotropic, afterload reducing, and coronary vasodilator properties. In a recent meta-analysis, authors evaluated eleven randomized controlled trials evaluating 1007 patients. (30) The studies were small and not of uniformly good quality. The authors evaluated treatment effect of each class of calcium channel blockers (diltiazem, verapamil, and dihy-dropyridine) on ischemia, MI, supraventricular tachycardia (SVT), and mortality. Calcium channel blockers were associated with nonsignificant trends toward decreased incidence of MI and death. However, among the eight studies which evaluated diltiazem alone, there were significant reductions in rates of ischemia (RR 0.34; 95% CI 0.18-0.63), SVT, MI, death, and major morbid events (RR, 0.31; 95% CI 0.11-0.88) without any significant increase in hypotension or bradycardia. Both diltiazem and verapamil significantly decreased perioperative SVT (diltiazem RR, 0.54; 95% CI 0.37-0.78 and verapamil RR, 0.44; 95% CI 0.20-0.94). The major limitations to the meta-analysis are the lack of sufficient statistical power to evaluate the endpoints and the suboptimal quality of some of the included studies. At this juncture, it appears that diltiazem is more effective than other calcium channel blockers in decreasing perioperative cardiac risk but this observation is based on limited data. It is unknown whether there is added benefit when CCBs are used with a beta blocker. Although the data are limited, it appears that perioperative CCBs are inferior to beta blockers.

Revascularization

Unless patients require coronary revascularization independently from the need for noncardiac surgery, there is no role for preoperative revascularization to reduce perioperative cardiac risk. This was established by the study of McFalls et al, who randomly assigned patients undergoing major vascular surgery to either preoperative coronary revascularization or no revascularization. (31) All patients received standard medical therapy. The proportion of patients receiving beta blockers and statins was similar between the two groups. Among the patients assigned to revascularization, 59% underwent percutaneous coronary intervention and 41% underwent coronary bypass surgery. In the first 30 days postoperatively, there were no statistically significant differences in the rate of myocardial infarction (P = 0.99) or death (P = 0.87) between medically treated and surgically treated patients. Similarly, a study by Godet et al showed that preoperative percutaneous coronary intervention did not significantly decrease postoperative cardiac events. (32)

Making the Leap to Less Testing

Many have pointed out the poor positive predictive value of noninvasive cardiac stress testing. The ACC/AHA guideline, RCRI, and others have all added needed structure to preoperative risk assessment. Controversy remains, however, regarding the use of noninvasive stress testing to stratify risk in these algorithms. Myocardial perfusion imaging and dobutamine stress echocardiogram (DSE) both have notoriously poor positive predictive values (4-25%), although their negative predictive values are excellent (93-100%). (7) A recent meta-analysis evaluating patients undergoing major vascular surgery found that DSE has a higher specificity than dipyridamole thallium or exercise stress testing. (33) Boersma et al added to our understanding of the use of these tests by confirming the low predictive value of DSE among clinically low risk patients receiving beta blockers. (22) They defined low risk patients as those with fewer than three of the following clinical characteristics: age [greater than or equal to]70, current angina, prior MI, congestive heart failure, prior CVA, diabetes mellitus, and renal failure. Low risk patients who received perioperative beta blockers and proceeded to surgery without further testing had a cardiac event rate of 0.8%. In patients with three or more clinical characteristics however, DSE provided additional prognostic information. Those patients with extensive ischemia on testing ([greater than or equal to]5 wall segments) had a 36% cardiac event rate despite perioperative beta blockers. (34) Thus, clinicians can identify a cohort of patients whose risk is sufficiently high in which beta blockers do not reduce risk. Cancellation of surgery, selection of a lower risk procedure, or coronary revascularization may be appropriate in this group.

Current Challenges and Questions

Coronary Artery Stenting

The advent of coronary artery stenting adds further complexity to perioperative management. Since placement of coronary stents denudes the arterial endothelial surface, the risk of intrastent thrombosis is high for the first several weeks after the procedure. The use of aspirin and clopidogrel decreases this risk, but if surgery must occur in the first several weeks after stent placement, the risk of intrastent thrombosis is high, and may occur even when aspirin and clopidogrel are continued. This is likely due both to the activation of the sympathetic nervous system and to the hypercoagulable state which occurs perioperatively. (35) A recent report of 40 patients who underwent noncardiac surgery within 6 weeks of coronary stent placement showed that 7 myocardial infarctions, 8 deaths, and 11 major bleeds occurred, and most of the deaths were cardiac in nature. All of the cardiac events occurred when surgery was within 2 weeks after stent placement. (36) In another report of 207 surgical patients with recent stents, cardiac event rates were 3.8% to 7.1% for each week of the 6 weeks following stent placement. There were no events after the six week point. (37)

The advent of drug-eluting stents may further complicate perioperative care. These stents prolong the re-endothelialization of coronary arteries, thus increasing the period of intrastent thrombotic risk for surgical patients with new stents. Manufacturer's guidelines recommend 3 months of combination antiplatelet therapy for patients with the sirolimus-eluting stent and 6 months for those with the paclitaxel-eluting stent. We recommend delaying elective noncardiac surgery until the antiplatelet therapy is completed. If a patient requires urgent surgery within 3 to 6 months after coronary stent placement, the medical consultant should evaluate the urgency of the surgery, the risk of hemorrhage at the surgical site, and the risk of major bleeding at nonoperative sites. If the type of surgery requires cessation of antiplatelet medications, the medical consultant should closely coordinate postoperative resumption of these medications with the surgeon. If angioplasty must occur before the surgical procedure, we recommend either plain angioplasty without a stent, or use of a bare metal stent followed by 2 weeks of aspirin and clopidogrel before proceeding to noncardiac surgery, since the highest risk of stent thrombosis appears to occur in the first two weeks. (38)

Aspirin Use

Traditionally, clinicians hold aspirin for 7 to 10 days before surgery to decrease perioperative bleeding. Recent information suggests that this may place patients at increased cardiac risk in the perioperative period. For example, in a study of 1236 patients admitted for acute coronary syndromes, 51 of the events (4.1%) were related to aspirin cessation within the prior 17 days, and 28 of these were related to preoperative or preprocedural aspirin cessation. (39) In a recent meta-analysis of 1930 patients, aspirin withdrawal preceded 10.2% of acute perioperative cardiovascular events. (40) This included cerebrovascular events, peripheral ischemia, and acute coronary syndrome. Indeed, prior studies have shown that withdrawal of aspirin can result in increased thromboxane [A.sub.2] with a concomitant risk of thrombotic events. (41) Although more prospective studies are needed, practitioners are reevaluating whether aspirin should be continued in the perioperative period for patients with known CAD as long as the risk of perioperative bleeding is acceptable. At the present time, medical consultants should consider the possibility of continuation of aspirin in the perioperative period on an individual basis, and discuss the risks and benefits with the surgeon.

Conclusion

Patients with few clinical risk factors and good functional status undergoing low- or intermediate-risk surgery are at low cardiac risk and can proceed to surgery without further testing. Patients who are at high cardiac risk due to unstable clinical circumstances (unstable angina, recent MI, recent coronary stenting, decompensated CHF, or severe valvular disease) should delay surgery and undergo the appropriate evaluation and treatment for the particular diagnosis. The optimal strategy to stratify and reduce risk for patients who have intermediate clinical risk factors and poor functional status who must undergo moderate- to high-risk surgery remains unclear. The ACC/AHA guideline offers a framework which, while not perfect, suggests criteria for noninvasive testing for this category of patients. The available literature points to dobutamine stress echocardiogram as having the most favorable test characteristics, but final choice depends on local availability and other clinical parameters such as the need to evaluate ventricular or valvular function.

We believe that perioperative beta blockade is efficacious in reducing postoperative cardiac events in moderate- to high-risk patients as defined by the RCRI or the ACC/AHA guideline. Adherence to explicit patient selection criteria would assure overall patient benefit. Dose titration to a target heart rate optimally reduces risk. Further research should clarify the optimal duration and timing of perioperative beta blockade.

We recommend:

1. Administer perioperative beta blockers for patients with two or more risk factors according to the Revised Cardiac Risk Index. Although the literature does not confidently establish the optimum duration of preoperative beta blockade, we recommend starting 1 to 2 weeks preoperatively and extending 1 to 2 weeks postoperatively.

2. Administer perioperative clonidine or diltiazem if beta blockers are contraindicated. However, diltiazem may also be contraindicated if the contraindication to beta blockers is conduction system disease.

3. Continue statin therapy in the perioperative period. Initiate statin therapy 2 to 4 weeks before surgery and continue until at least one week after surgery for patients who are candidates for perioperative beta blockers and who are not already taking statins.

4. Continue low-dose aspirin therapy in patients with known CAD if compatible with the type and extent of surgery.

Acknowledgments

We wish to thank Karen Pleasant for her excellent assistance in the preparation of this manuscript.

References

1. Poldermans D, Boersma E. Beta-blocker therapy in noncardiac surgery. N Engl J Med 2005;353:412-414.

2. Fleisher LA. Strategies to reduce cardiac risk in noncardiac surgery: where are we in 2005? Anesthesiology 2005;102:881-882.

3. Fleisher LA. Preoperative cardiac evaluation. Anesthesiol Clin North America 2004;22:59-75.

4. Ellis SG, Hertzer NR, Young JR, et al. Angiographic correlates of cardiac death and myocardial infarction complicating major nonthoracic vascular surgery. Am J Cardiol 1996;77:1126-1128.

5. Dawood MM, Gutpa DK, Southern J, et al. Pathology of fatal perioperative myocardial infarction: implications regarding pathophysiology and prevention. Int J Cardiol 1996;57:37-44.

6. Priebe HJ. Triggers of perioperative myocardial ischaemia and infarction. Br J Anaesth 2004;93:9-20.

7. Maddox TM. Preoperative cardiovascular evaluation for noncardiac surgery. Mt Sinai J Med 2005;72:185-192.

8. Goldman L, Caldera DL, Nussbaum SR, et al. Multifactorial index of cardiac risk in noncardiac surgical procedures. N Engl J Med 1977;297:845-850.

9. Eagle KA, Berger PB, Calkins H, et al. ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery update: 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). American College of Cardiology Web site. Available at: http://www.acc.org/qualityandscience/clinical/guidelines/perio/perioupdate_index.htm.

10. 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;100:1043-1049.

11. Eagle KA, Rihal CS, Mickel MC, et al. Cardiac risk of noncardiac surgery: influence of coronary disease and type of surgery in 3368 operations. CASS Investigators and University of Michigan Heart Care Program. Coronary Artery Surgery Study. Circulation. 1997;96:1882-1887.

12. Reilly DF, McNeely MJ, Doerner D, et al. Self-reported exercise tolerance and the risk of serious perioperative complications. Arch Intern Med 1999:159:2185-2192.

13. Hlatky MA, Boineau RE, Higginbotham MB, et al. A brief self-administered questionnaire to determine functional capacity (the Duke Activity Status Index). Am J Cardiol 1989;64:651-654.

14. Myers J, Do D, Herbert W, et al. A nomogram to predict exercise capacity from a specific activity questionnaire and clinical data. Am J Cardiol 1994;73:591-596.

15. Mangano DT, Layug EL, Wallace A, et al. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med 1996;335:1713-1720.

16. 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;341:1789-1794.

17. Brady AR, Gibbs JS, Greenhalgh RM, et al. Perioperative beta-blockade (POBBLE) for patients undergoing infrarenal vascular surgery: results of a randomized double-blind controlled trial. J Vasc Surg 2005;41:602-609.

18. Yang H, Raymer K, Butler R, et al. The effects of perioperative beta-blockade: results of the Metoprolol after Vascular Surgery (MaVS) study, a randomized controlled trial. Am Heart J 2006;152:815-818.

19. Juul AB, Wetterslev J, Gluud C, et al. Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial. BMJ 2006;24:1482-1485.

20. Lindenauer PK, Pekow P, Wang K, et al. Perioperative beta-blocker therapy and mortality after major noncardiac surgery. N Engl J Med 2005;353:349-361.

21. Devereaux PJ, Beattie WS, Choi PT, et al. How strong is the evidence for the use of perioperative beta blockers in non-cardiac surgery? Systematic review and meta-analysis of randomised controlled trials. BMJ 2005;331:313-321.

22. Boersma E, Poldermans D, Bax JJ, et al. Predictors of cardiac events after major vascular surgery: Role of clinical characteristics, dobutamine echocardiography, and beta-blocker therapy. JAMA 2001;285:1865-1873.

23. Redelmeier D, Scales D, Kopp A. Beta blockers for elective surgery in elderly patients: population based, retrospective cohort study. BMJ 2005;331:932.

24. Fleisher LA, Beckman JA, Freeman WK, et al. ACC/AHA 2006 guideline update on perioperative cardiovascular evaluation for noncardiac surgery: focused update on perioperative beta-blocker therapy: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery) developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society for Vascular Medicine and Biology. J Am Coll Cardiol 2006;47:2345-2355.

25. Wallace AW, Galindez D, Salahieh A, et al. Effect of clonidine on cardiovascular morbidity and mortality after noncardiac surgery. Anesthesiology 2004;101:284-293.

26. Durazzo AE, Machado FS, Ikeoka DT, et al. Reduction in cardiovascular events after vascular surgery with atorvastatin: a randomized trial. J Vase Surg 2004;39:967-976.

27. Biccard BM, Sear JW, Foex P. Statin therapy: a potentially useful perioperative intervention in patients with cardiovascular disease. Anaesthesia 2005;60:1106-1114.

28. Poldermans D, Bax JJ, Kertai MD, et al. Statins are associated with a reduced incidence of perioperative mortality in patients undergoing major noncardiac vascular surgery. Circulation 2003;107:1848-1851.

29. Lindenauer PK, Pekow P, Wang K, et al. Lipid-lowering therapy and in-hospital mortality following major noncardiac surgery. JAMA 2004;291:2092-2099.

30. Wijeysundera DN, Beattie WS. Calcium channel blockers for reducing cardiac morbidity after noncardiac surgery: a meta-analysis. Anesth Analg 2003;97:634-641.

31. McFalls EO, Ward HB, Moritz TE, Goldman S, et al. Coronary-artery revascularization before elective major vascular surgery. N Engl J Med 2004;351:2795-2804.

32. Godet G, Riou B, Bertrand M, et al. Does preoperative coronary angioplasty improve perioperative cardiac outcome? Anesthesiology 2005;102:739-746.

33. Kertai MD, Bax JJ, Heijenbrok-Kal MH, et al. A meta-analysis comparing the prognostic accuracy of six diagnostic tests for predicting perioperative cardiac risk in patients undergoing major vascular surgery. Heart 2003;89:1327-1334.

34. Boersma E, Kertai MD, Schouten O, et al. Perioperative cardiovascular mortality in noncardiac surgery: validation of the Lee cardiac risk index. Am J Med 2005;118:1134-1141.

35. Bradbury A, Adam D, Garrioch M, et al. Changes in platelet count, coagulation and fibrinogen associated with elective repair of asymptomatic abdominal aortic aneurysm and aortic reconstruction for occlusive disease. Eur J Vasc Endovasc Surg 1997;13:375-380.

36. Kaluza G, Joseph J, Lee JR, et al. Catastrophic outcomes of noncardiac surgery soon after coronary stenting. J Am Coll Cardiol 2000;35:1288-1294.

37. Wilson SH, Fasseas P, Orford JL, et al. Clinical outcome of patients undergoing non-cardiac surgery in the two months following coronary stenting. J Am Coll Cardiol 2003;42:234-240.

38. Weitz HH. How soon can a patient undergo noncardiac surgery after receiving a drug-eluting stent? Cleve Clin J Med 2005;72:818-820.

39. Ferarri E, Benhamou M, Cerboni P, et al. Coronary syndromes following aspirin withdrawal: a special risk for late stent thrombosis. J Am Coll Cardiol 2005;45:456-459.

40. Burger W, Chemnitius JM, Kneissl GD, et al. Low-dose aspirin for secondary cardiovascular prevention--cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation--review and meta-analysis. J Intern Med 2005;257:399-414.

41. Beving H, Zhao C, Albage A, et al. Abnormally high platelet activity after discontinuation of acetylsalicylic acid treatment. Blood Coagul Fibrinolysis 1996;7:80-84.

Donna L. Mercado, MD, David Y. Ling, MD, and Gerald W. Smetana, MD

From the Division of General Internal Medicine and Geriatrics, Baystate Medical Center, Tufts University School of Medicine, and the Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

Reprint requests to Donna L. Mercado, MD, Department of Medicine, Bay-state Medical Center, 759 Chestnut Street, Springfield, Massachusetts 01199. Email: [e-mail]

Dr. Smetana discloses a financial relationship with Harvard Medical International/Novartis Pharma Schweiz (honorarium for course development). Drs. Mercado and Ling have no disclosures to declare.

Accepted July 11, 2006.

RELATED ARTICLE: Key Points

* Postoperative cardiac complications are common and are a major cause of perioperative morbidity and mortality.

* The Revised Cardiac Risk Index and the American Heart Association/American College of Cardiology guidelines on preoperative cardiovascular evaluation each provide tools to estimate cardiac risk before surgery.

* Recent evidence has questioned the value of perioperative beta blockers; benefit remains likely for intermediate- and high-risk patients.

* Diltiazem, clonidine, and statins each may reduce risk in selected patients.

* Coronary revascularization does not reduce perioperative cardiac risk for patients with stable coronary artery disease.

Table 1. Clinical predictors of perioperative cardiac risk

Major                    Intermediate         Minor

Acute or recent MI       Mild angina          Advanced age
Unstable angina          Prior MI             Abnormal ECG
Decompensated CHF        Compensated CHF      Rhythm other than sinus
Significant arrhythmias  Diabetes mellitus    History of stroke
Severe valvular disease  Renal insufficiency  Uncontrolled hypertension

Adapted with permission from ACC/AHA Task Force Report. Circulation
2002;105:1257-1267.
MI, myocardial infarction; CHF, congestive heart failure; ECG,
electrocardiogram.

Table 2. Revised Cardiac Risk Index

High-risk surgical procedure (intraperitoneal, intrathoracic,
  suprainguinal vascular)
History of ischemic heart disease
History of congestive heart failure
History of cerebrovascular disease
Preoperative treatment with insulin
Preoperative serum creatinine >2.0 mg/dL
Risk of postoperative cardiac events

Points     Class  Risk

0          I       0.4%
1          II      0.9%
2          III     6.6%
3 or more  IV     11%

Each risk factor is assigned one point.
Adapted with permission from Circulation 1999;100:1043-1049.

Table 3. Surgery-specific cardiac risks

High (>5%)             Intermediate (<5%)             Low (<1%)

Emergent surgery       Carotid endarterectomy         Endoscopic
                                                        procedures
Aortic or other major  Head and neck surgery          Superficial
  vascular surgery                                      procedures
Peripheral vascular    Intraperitoneal intrathoracic  Cataract surgery
  surgery                surgery
Large fluid shift and  Orthopedic surgery             Breast surgery
  blood loss

Adapted with permission from ACC/AHA Task Force Report. Circulation
2002;105:1257-1267.

Table 4. The number needed to treat (NNT) to prevent in-hospital death
using perioperative statin therapy based on the Revised Cardiac Risk
Index

Points  NNT (95% CI)

0       186 (168-214)
1       103 (93-119)
2        60 (54-69)
3        39 (35-45)
4        30 (27-35)