Perioperative Myocardial Infarction and Changes in Left Ventricular Performance Related to Coronary Artery Bypass Graft Surgery

COLLECTIVE REVIEW

Perioperative Myocardial Infarction and Changes in Left Ventricular Performance Related to Coronary Artery Bypass Graft Surgery Arthur J. Roberts, M.D.

ABSTRACT Recent advances in perioperative management and surgical technique have been associated with low operative mortality and a high incidence of symptomatic relief in patients undergoing coronary artery bypass graft (CABG)operations. The frequency and importance of perioperative myocardial infarction (MI) and immediate as well as longterm changes in left ventricular (LV) performance are factors of considerable current interest in any critical analysis of the effectiveness of CABG surgery. The present review describes the effects of patient selection, anesthetic techniques, and newer methods of myocardial protection as they relate to perioperative MI and LV performance. In addition, newer tests useful in the diagnosis of perioperative MI are discussed. The application of noninvasive techniques for the serial determination of LV performance and myocardial perfusion in CABG operations is also described.

Coronary artery bypass grafting (CABG) has earned increasing acceptance as a physiological treatment for coronary artery disease. Nevertheless, controversy exists regarding the frequency and importance of acute myocardial infarction (MI) occumng during the perioperative period. The influence of CABG operation on left ventricular (LV) performance and changes in myocardial perfusion has also been debated. The reported incidence of perioperative MI ranges from 2 to approximately 40% [I, 21. Many factors may account for this wide variation, including type of intraoperative myocardial protection, experience of the surgical team, anesthetic technique, and patient selection. Fur-

From the University of Florida Medical School, Division of Cardiothoraac Surgery. Address reprint requests to Dr. Roberts, Director of Adult Cardiac Surgery, Department of Surgery, J . Hillis Miller Health Center, University of Florida, Gainesville, FL 32610.

thermore, the criteria for defining perioperative MI are imprecise. At present, electrocardiographic, enzymatic, hernodynamic, echocardiographic, and scintigraphic methods are most commonly used in making the diagnosis of perioperative MI. Many of the same procedures are also useful in determining changes in LV performance related to CABG operation. This collective review examines the utility of newer techniques in coronary bypass grafting. Preoperative Evaluation Since operative mortality is largely related to the level of preoperative myocardial damage [3], patient selection may be influenced by new techniques that help distinguish between reversible and irreversible LV wall motion abnormalities. Nitroglycerin ventriculography is one such technique. Preoperative improvement in segmental wall motion in response to nitroglycerin has been shown to correlate with improvement in contraction of the same region of the left ventricle following CABG operation [4]. Dynamic perfusion scintigraphy using thallium 201 may also identify myocardium with reversible ischemia, thereby improving operative selection [5]. And hernodynamic and electrocardiographic changes induced by atrial pacing during cardiac catheterization may aid in revealing stressinduced ischemia. This information may help to characterize patients with vague symptoms or mild to moderate coronary artery obstructions. Recent developments in radionuclide ventriculography may prove useful in defining operative risk. Reversible wall motion abnormalities can be detected noninvasively [ 6 ] ,and serial observations can help determine both the optimal timing of CABG operation and the likelihood of hemodynamic improvement subsequent to myocardial revascularization [7. The presence and extent of symptomatic preoperative myocardial ischemia may in-

208 OOO3-4975/83/020208-18$01.50@ 1982 by The Society of Thoracic Surgeons

209 Collective Review: Roberts: Perioperative Myocardial Infarction

fluence the outcome of surgical intervention [8]. In patients with unstable angina, it is important but often difficult to exclude ongoing MI. Evaluation of these patients includes serial assessments of both the ECG and routine as well as myocardial-specific serum enzymes. In addition, technetium 99m pyrophosphate myocardial scans may aid in the identification of acute MI in these patients. However, as many as one-third of patients with unstable angina may have a diffusely positive Y'"Tc-PYP scintigram when there is neither electrocardiographic nor enzymatic evidence of myocardial necrosis [9]. Controversy exists as to whether this situation represents a process of undetected microinfarction [lo], or a false positive scintigram [9]. Moreover, the diagnosis of myocardial necrosis may also be missed by the failure to identify transient elevations of the myocardial isoenzyme of serum creatine kinase (CK-MB) when serial blood samples are not obtained frequently in such patients. Consequently, a small but probably important number of patients with refractory ischemia who are considered for operation may have undetected active myocardial necrosis preoperatively. My colleagues and I have been impressed by the finding that myocardial revascularization in the presence of evolving myocardial necrosis is associated with a relatively high incidence of morbidity and mortality [7, 8); therefore, we tend to emphasize medical stabilization prior to CABG operation [7]. Some groups, however, have reported good results with myocardial revascularization during the early stages of myocardial necrosis [ll]. Further prospective randomized studies are needed to clarify optimal patient management in the acute and subacute phases of myocardial necrosis. Another group of patients that is encountered with increasing frequency is the subset with coronary artery spasm [ 121. Although surgical results in this group appear to be somewhat inferior to those in patients who have only fixed organic coronary obstruction without spasm [13], a greater awareness of the potential problems may lead to a more common preoperative diagnosis of spasm, as well as altered perioperative patient management and, hopefully, fewer perioperative complications related to this entity [14].

Perioperative Physiological Monitoring: Early Identification and Reversal of Myocardial Ischemia The goal of perioperative monitoring is to identify early hemodynamic or electrocardiographic abnormalities, or both. Consequently, correction of abnormal trends might avoid severe myocardial ischemia or cell death. Over the past several years, flow-directed pulmonary artery catheters have been used with increasing frequency in CABG operations. Advantages of pulmonary artery catheters include the ability to measure pulmonary artery pressure and pulmonary capillary wedge pressure, as well as to determine cardiac output by the thermodilution technique. Considering the increasing application of this monitoring device, the rate of morbidity and mortality reported subsequent to its use has been remarkably low [15]. Nevertheless, pulmonary artery perforation, pulmonary infarction, and puncture of the carotid artery are occasionally seen. Intraoperatively, flowdirected pulmonary artery catheters are extremely useful in detecting the early elevation in LV filling pressure that frequently precedes electrocardiographic evidence of severe myocardial ischemia (Fig 1).However, more experience is needed to determine if routine or selective use of these catheters is advisable in CABG operations. Another monitoring technique that has been applied with increasing frequency is the modified precordial V5 electrogram. This device has also enabled early identification of myocardial ischemia. An example of the increased sensitivity provided by the modified precordial electrode compared with standard ECG limb leads in the detection of S-T segment abnormalities is shown in Figure 2. The physiological consequences of coronary artery disease may be reliably thought of as an imbalance between myocardial oxygen supply and demand [12]. Studies have shown that demand is exceeded when the rate pressure product is more than 22,000 mm Hg x number of beats per minute in patients with coronary artery disease. Kaplan and colleagues [16] have reported that maintaining the rate pressure product below 12,000 minimizes perioperative myocardial ischemia.

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CONTROL ECG ARTERIAL BLOOD PRESSURE (mmHg) PULMONARY

-cw-

"'[ 100

-ul

100 80

40

40

PRESSURE RATE PRESSURE PRODUCT

DURING EARLY ISCHEMA

20 10

12.231

9,79e

Fig 1 . Intraoperative value of the flow-directed pulmona y artery catheter in the early identification and successful treatment of myocardial ischemia. (PCWP = pulmonary capillary wedge pressure.1

I

P

m

AVR

AVL

AVF

v5

AVR

AVL

AVF

"5

Fig 2. lntraoperative sensitivity of the modified precordial electrogram (V5)compared with that of the standard limb leads (AVR, AVL, AVF).

Isom and co-workers [17] reported in 1975 that myocardial injury, as shown by release of the myocardial-specific isoenzyme CK-MB, often occurred during the critical induction and pre-cardiopulmonary bypass (CPB) periods. Since that time, intraoperative radionuclide ventriculography has also shown LV functional impairment during the induction period [MI. The suggestion has been made that appropriate anesthetic management during this vulnerable period may decrease perioperative myocardial damage. Although hypotension and tachycardia are known to be serious intraoperative problems, hypertensive episodes associated with the induction of anesthesia may also cause myocardial ischemia. Perioperative hypertension has been noted frequently in patients undergoing CABG procedures, and the associated biochemical and hemodynamic abnormalities underlying these responses have been described [19]. Kaplan and associates [16] have shown that intravenous nitroglycerin improved electrocardiographic and hemodynamic abnormalities during CABG-associated hypertension in the vulnerable pre-CPB period. Additionally, Moore and colleagues [20] demonstrated that the flow-directed pulmonary artery catheter was a major factor in the early diagnosis of abnormalities in preload and cardiac output, prompting specific treatment and resulting in decreased operative mortality in patients with left main coronary artery obstruction undergoing CABG operations. My colleagues and 1have noted that routine continuous monitoring of the pulmonary artery pressure, the precordial electrogram, and the rate pressure product, coupled with the liberal use of intravenous nitroglycerin, has permitted the identification and early treatment of intraoperative myocardial ischemia. Consequently, we have found that the presence of serum CK-MB was noted in only 1 of 30 patients (3.3%),in contrast to the initial report of Isom and colleagues [17] in which over 30% of patients had an elevation of the same isoenzyme prior to CPB. Although clinical studies concerning myocardial isoenzyme release patterns may not accurately quantify salvage of myocardium that might otherwise have been permanently damaged, we believe the implication is that well-directed hemodynamic and

211 Collective Review: Roberts: Perioperative Myocardial Infarction

electrocardiographic monitoring is helpful in the management of patients undergoing CABG operations.

Anesthetic Techniques Recent advances in cardiac surgical anesthesiology have suggested that the choice of an anesthetic for myocardial revascularization may play an important role in subsequent perioperative myocardial damage and LV function. Lowenstein [21] popularized the use of high-dose (0.5 to 3 mg per kilogram) morphine as an anesthetic agent for cardiac surgery. He found that a 2 mg per kilogram dose did not greatly affect cardiac output, systemic vascular resistance, blood pressure, or heart rate in normal supine patients. Nevertheless, later reports have shown that morphine may produce marked changes in systemic and coronary vascular resistance, as well as increased venous capacitance and slightly decreased myocardial contractility [22]. Morphine anesthesia has also been found to be associated with elevated levels of circulating catecholamines. Subsequent increases in heart rate and arterial blood pressure following endotracheal intubation and median sternotomy are common in patients with coronary artery disease who were anesthetized with morphine [23]. In another morphine-related study, blood requirements during morphine-nitrous oxide anesthesia were shown to be substantially increased compared with those for other standard anesthetic techniques; there was also a greater need for postoperative mechanical ventilation ~41. Although morphine anesthesia has proven reliable in CABG surgery, its shortcomings have fostered renewed interest in alternative anesthetic agents [25].Halothane is a myocardial depressant [26], but it does not produce the sympathoadrenal stimulation caused by morphine during induction and CPB. Bland and Lowenstein [27] recently found that in the nonfailing canine heart, halothane decreases myocardial oxygen consumption and lessens the severity of experimentally induced myocardial ischemia. Our clinical experience with coronary bypass procedures has shown that systemic hypertension is less common with halothane and that prolonged postoperative mechanical ventilation

is seldom required after halothane anesthesia. A detrimental effect of this technique is the uncommon postoperative occurrence of halothane hepatitis. Several clinical studies have shown that halothane is associated with a low level of myocardial damage, as determined by intraoperative serum CK-MB release (251 in patients without severe LV dysfunction who undergo CABG procedures. High-dose fentanyl-oxygen anesthesia has been suggested as an alternative to morphine in patients with minimal cardiac functional reserve. The preliminary efficacy of this technique has been demonstrated in patients undergoing CABG operations [28]. While no available anesthetic technique is without drawbacks, the judicious application, with careful perioperative monitoring, of halothane, morphine, or fentanyl anesthesia may be conducted with reasonable safety and minimal depression of LV function. Further randomized prospective clinical studies are required to determine which technique, if any, is superior in patients undergoing CABG operations.

Myocardial Protection At present, the best method of myocardial protection during CABG operation is uncertain, but there has been considerable experimental and clinical research on this topic (291. Most CABG operations in the United States are performed utilizing hypothermic potassium crystalloid cardioplegia [30]. Although excellent clinical results have been reported with this technique [31], some investigators think that the addition of high potassium concentrations to a bloodbased medium is more beneficial [32]. Several less commonly used techniques for myocardial protection include CABG procedures performed using intermittent aortic cross-clamping under hypothermic conditions (331 or continuous cross-clamping with topical hypothermia [MI. Local coronary artery snaring in the presence of ventricular fibrillation is occasionally employed 1351. We believe that regardless of the vehicle chosen for a cardioplegic technique, the cardioplegic delivery system is important. This system shouId allow careful control of pressure, volume, flow rate, temperature, and mixing.

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--

) ; A

Arterial Line to Patient

Water Pump

Fig 3 . Cardioplegia delivery system developed at Northwestern Medical Center in 2979. This system permits control over pressure, volume, pow, and temperature during administration of cardioplegia.

The delivery system we developed at Northwestern Medical Center in 1979 is shown in Figure 3. Our clinical experience has shown that multidose hypothermic potassium cardioplegia [31], hypothermic intermittent aortic cross-clamping [33], and cold blood cardioplegia all provide excellent preservation of LV performance related to CABG operation. Although the cardiac surgical literature is filled with reports on the relative efficacy of various types of myocardial preservation, we agree with Ebert [36], who states that the large number of solutions and components used in myocardial protection make it difficult to prove one method superior to others. Furthermore, none of the specialized measures may be as important as the techniques of its application; thus, the safe period of cardiac arrest probably varies with each surgeon. Recent experiments suggest that myocardial protection may be improved by strengthening cardioplegic solutions through the addition of high-energy phosphate compounds [37], amino acids [38], or calcium blockers (391. In addition, determining the most appropriate level of myocardial hypothermia during cardioplegic arrest [40], ensuring more rapid and homogenous de-

livery of cardioplegic solutions distal to highgrade proximal coronary artery obstructions [41],and developing methods of modifying the perfusate during the initial reperfusion period following the release of the aortic cross-clamp [42] have been identified as important considerations in the diminution of perioperative myocardial damage during CABG operation. The Nature of Perioperative Myocardial Damage Relatively little is known about the specific events that result in the deposition of atheromatous material in a coronary artery. Fixed coronary artery disease is only one of the pathophysiological factors involved in MI, since coronary spasm, platelet aggregation and other variables contributing to the inequality of myocardial oxygen supply and demand have recently been shown to be important causes of myocardial ischemia in both the presence and absence of discrete atherosclerotic lesions [43]. While the role of coronary spasm in the development of perioperative myocardial damage is only speculative at present, it has been identified as potentially important [14]. Metabolic and hemodynamic changes associated with CABG operation may influence oxygen supply and demand relationships during the perioperative period. Such changes may be unrelated to prolonged aortic cross-clamping or technical error. Local myocardial changes in pH, temperature, oncotic pressure, and osmolality may adversely affect myocardial energy

213 Collective Review: Roberts: Perioperative Myocardial Infarction

processes. Hemodynamic abnormalities such as elevated preload, increased afterload, or severe tachycardia may increase oxygen consumption, adversely influencing myocardial cellular integrity. Moreover, the specific method of myocardial protection may be inadequately applied. For example, a cardioplegic solution may be delivered to the myocardium under extremely high perfusion pressure, or the effectiveness of cardioplegia may be lessened by abundant extracoronary collateral blood flow, allowing myocardial rewarming and the resumption of energy-demanding fibrillatory movements during global myocardial ischemia. Indeed, the duration of myocardial ischemia tolerated by a given patient without evidence of myocardial decompensation is variable and somewhat unpredictable. However, certain factors, such as LV hypertrophy, are known to influence this critical time relationship, and must be evaluated individually for each patient. Myocardial necrosis in the perioperative period is also complicated by the presence of new perfusion from the bypass graft or grafts. While technical failures are certainly major factors in the pathogenesis of perioperative myocardial damage [MI, other possible mechanisms must include myocardial reperfusion injury sustained through widely patent grafts after a period of operative nonperfusion [45]. The pathophysiology of perioperative myocardial damage is often unclear; nonetheless, the incidence of low cardiac output syndrome and operative mortality subsequent to perioperative MI has decreased in recent years. Further investigations devoting more attention to the cellular and subcellular levels may aid in better understanding this trend. The Diagnosis of Perioperative Myocardial Infarction Electrocardiography The ECG has been the historical standard for the diagnosis of perioperative MI. Experience has shown that the ECG may not always be dependable in the cardiac surgical setting. Still, the diagnosis of perioperative MI is likely with the postoperative appearance of new, persistent Q waves of 0.04 second duration or longer, or new QS deflections associated with characteris-

tic evolutionary changes in the S-T segment and T waves [MI. The diagnosis of perioperative myocardial ischemic injury is probable with any of the following developments: (1)flat S-T segment depressions greater than 2 mm in leads to the left ventricle, especially when lasting more than 48 hours; (2) deep T-wave inversions persisting for more than 48 hours; (3) serious ventricular arrhythmias, such as ventricular tachycardia or fibrillation; and (4) the appearance of a shift in electrical axis or a new bundle branch block. Much of the controversy over the electrocardiographic diagnosis of perioperative MI is related to the importance of new Q waves or S-TT wave abnormalities, or both. In a large necropsy series, Horan and colleagues [46] observed an overall specificity of 89% and a sensitivity of 61% for abnormal Q waves in nonsurgical patients suspected of having acute myocardial necrosis. Although similar relationships have not been accurately determined in patients undergoing CABG operations, the implication is that not all Q waves are synonymous with acute myocardial necrosis. Since a new Q wave may, by itself, be an inaccurate standard for perioperative MI, the relationship between a new Q wave and the development of a new wall motion abnormality as determined by left ventriculography assumes greater importance. Postoperative ventriculographic studies have shown that new Q waves are usually associated with new areas of ventricular asynergy [47, 481. However, this relationship has been questioned by several investigators. In fact, Bassan and co-workers [49] have suggested that new Q waves may be unmasked by improved contraction of the contralateral ventricular segment. Other authors have shown that some patients who develop new Q waves have improved postoperative ventriculograms and patent grafts [50], or show evidence of the disappearance of these abnormal Q waves within several days of their appearance after aortocoronary bypass grafting [51]. Based on available data, it appears that around 20% of new Q waves developing after CABG operation may be associated with little or no readily detectable perioperative myocardial necrosis.

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The appearance of postoperative electrocardiographic abnormalities-T-wave inversions, S-T segment deviations, or severe ventricular arrhythmias with or without axis shift or bundle-branch block-has usually been considered nondiagnostic, but may suggest acute myocardial injury. Such changes are common postoperatively; they may reflect pericarditis, minor surgical trauma, electrolyte imbalance, hypothermia, hypoglycemia, acidosis, or pancreatitis. While most of these changes appear clinically to be well tolerated and are rarely associated with low cardiac output syndrome, Hultgren and co-workers [MI have estimated that as many as 50% of such nonspecific episodes may indicate acute myocardial necrosis, especially when serum enzyme levels are also abnormally elevated. Furthermore, postoperative ventriculograms in patients with so-called nonspecific perioperative S-T segment or ‘rwave changes may show a high incidence of new regional LV wall motion abnormalities [48]. Nevertheless, our impression is that most patients with only nonspecific perioperative electrocardiographic changes have very few global contraction abnormalities as determined by radionuclide ventriculography, and their postoperative courses are usually benign [52].

Serum Cardiac-related Enzymes and Isoenzymes The specificity and sensitivity of routine cardiacrelated serum enzymes have been somewhat disappointing due to a multiplicity of factors contributing to increased values after CABG surgery [I, 21. In addition, there is wide variability in the application of the laboratory methods used to determine serum enzyme levels. In our experience, individual postoperative serum enzyme values that fall outside the range of the mean plus two standard deviations for a previously determined cohort of selected, uncomplicated CABG surgical patients, operated on at a given institution using the institution’s standard techniques, are indicative of perioperative myocardial damage at that institution [52, 531. Accurate comparison of absolute levels of postoperative isoenzyme values from different institutions may be difficult. There are several commonly observed no:n-

cardiac causes for postoperative elevations in serum enzyme levels. Blood levels of serum glutamic-oxaloacetic transaminase (SGOT) and creatine kinase are elevated by musculoskeletal operative trauma, while serum lactic dehydrogenase (LDH) may be high due to hemolysis, pulmonary infarction, or renal cortical damage. In addition, the level of SGOT may be elevated secondary to right heart failure, passive hepatic congestion, hepatic necrosis, or transfusion reactions. Despite problems in using routine serum enzyme levels to accurately diagnose perioperative MI, several teams of investigators have attempted to delineate this relationship. AssadMorel1 and colleagues [54] found that abnormal elevations in SGOT levels were only specific for transmural MI (new Q wave) in approximately 60% of patients after CABG operation. However, when extreme elevations of SGOT values are observed postoperatively, perioperative MI is more likely. Rose and co-workers [55] concluded that an SGOT value greater than 200 IU per liter is reasonably reliable in separating patients with perioperative MI from those without infarction. Similarly, when the peak serum CK level is greater than 2,000 IU per liter, and especially when high levels of serum CK are maintained for a prolonged period postoperatively, the likelihood of perioperative MI is increased 11, 21. Some researchers have suggested that combinations of different standard serum enzyme levels may improve the accuracy of detecting perioperative MI after CABG operations, but our group and others have not found this suggestion particularly helpful [2, 541. Because of the variability in routine serum enzyme determinations, we have been encouraged to regard these values with considerable skepticism in the perioperative period. In attempts to increase sensitivity and specificity, the clinical application of myocardialspecific isoenzymes has found wide usage in recent years. Dixon and associates [56] initially studied the role of serum CK-MB in 1973. The same group later found that more frequent intraoperative serum sampling revealed demonstrable serum CK-MB in 77%of patients. Using what they considered a more sensitive biochem-

215 Collective Review: Roberts: Perioperative Myocardial Infarction

ical assay, Klein and co-workers [57] more recently showed that the serum CK-MB fraction is elevated postoperatively in approximately 90% of all patients undergoing CABG operation. These studies suggest that biochemical methodology and sampling techniques affect results obtained with perioperative isoenzyme analysis. Nevertheless, perioperative elevation of serum CK-MB levels is common. Therefore, methods to define "substantial" or "abnormal" elevation in postoperative serum CK-MB are needed. Initial efforts to determine this relationship have been made (52, 531. Clinical studies have described peak elevations in serum CK-MB as occurring from 1 to 6 hours postoperatively [I, 58, 591. However, when analysis of serum CK-MB levels is used with scintigraphic and electrocardiographic methods to detect perioperative MI, greater diagnostic accuracy is achieved [57, 591. Although the relationship between the magnitude of serum CK-MB release and the duration of continuous aortic cross-clamping appears to be variable, this enzymatic evaluation may provide an index of the adequacy of myocardial protection chosen for CABG procedures [58]. The construction of time-activity curves has also been useful in the diagnosis of perioperative MI related to CABG operation [58, 591. The perioperative rise and fall of serum CK-MB following myocardial revascularization is shown in Figure 4. Several factors are associated with postoperative elevations of serum CK-MB levels. The most common conditions are surgical trauma and global myocardial ischemia; other variables include anesthetic technique and perioperative pharmacological therapy, which may alter the disappearance rate of the isoenzyme. In addition, hypothermia and intraoperative defibrillation may influence myocardial enzyme liberation. The shape of the serum CK-MB curve may suggest myocardial damage by having a prolonged plateau or, in cases of recurrent postoperative necrosis, a second peak. A profile of serum CK-MB activity based on frequent perioperative blood sampling may prove an effective means of determining "abnormal" liberation of isoenzyme secondary to perioperative MI from the usual elevation secondary to operative intervention.

-

EXPECTED RESPONSE

24

0

48

TIME (hours)

ABNORMAL RESPONSE 400

I1

loo O 0

\ 1

2

3

4

5

W 6

TIME (days)

Fig 4 . Perioperative pattern of the time-release curves for myocardial isoenzymes of serum creatine kinase (CK-MB) and serum lactic dehydrogenase (LDHI)in patients undergoing coronay artery bypass grafting. (Reproduced with permission of the publisher from Roberts A], Spies SM, Sanders JH,et al: Serial assessment of 14t ventricular performance following coronay artery bypass grafting. ] Thorac Cardiovasc Surg 81 :69, 1981.)

At present, the clinical importance of postoperative elevations of serum CK-MB remains uncertain. Initial attempts to relate MI size and peak or total release of serum CK-MB have generally been inconclusive [60]. Our preliminary experience suggests that even abnormal postoperative elevations in serum CK-MB levels, unless associated with the clinical low cardiac output syndrome, may not be associated with depression in global left ventricular ejection fraction (LVEF)early after CABG operation [52]. The clinical application of the isoenzyme technique has proven useful in excluding the diagnosis of acute MI in patients with unstable angina who are being considered for operation [61]. At least one study has documented the relationship between different findings for perioperative MI and postoperative contrast ventriculography [47]. This report showed that one year after CABG operation, electrocardiographic evidence for myocardial necrosis was 100% specific, and serum analysis of CK-MB

216 The Annals of Thoracic Surgery Vol 35 No 2 February 1983

clearance was 78% specific for new asynergy. However, these tests were only 20% and 54% sensitive, respectively. In addition, they showed that 46% of patients with new asynergy unrelated to apical LV venting did not have evidence of QRS changes or appearance of serum CK-MB perioperatively. Some investigators have suggested that serum LDH isoenzyme analysis may be as effective as analysis of serum CK-MB as a means of detecting myocardial necrosis after CABG operation [62]. The reversal of the normal LDH, :LDHp ratio has been cited as substantial evidence for the presence of MI [62]. Although this serum enzyme assay has had less perioperative application than serum CK-MB analysis, further evaluation may be warranted.

Myocardial Infarct Scintigraphy There has been a great deal of recent interest in "hot spot" or infarct-avid imaging. While several radiopharmaceutical agents have been tried for infarct detection, none have achieved the clinical success of technetium 99m pyrophosphate [63]. At least 3 gr of myocardial necrosis must be present to scintigraphically identify acute MI. In addition, 99mTc-PYPmyocardial uptake is greatest in myocardial regions where coronary blood flow has decreased to 20 to 40% of normal levels. The timing between the onset of MI and the acquisition of the 99mTc-PYP image is also of critical importance in the accurate identification of myocardial necrosis. Scintigrams using %"'Tc-PYP become positive approximately 12 hours after acute MI, and become increasingly positive during the first 24 to '72 hours after infarction. Most positive images fade, or become negative, or both approximately 6 to 10 days after the clinical event, but a small percentage of patients-often those with large anterior wall infarctions-maintain a persistently positive scintigram for long periods. Such patients have been found to have a high incidence of congestive heart failure [63]. Since pyrophosphate binds to calcium, the sternum and ribs are visualized in a 99mTc-PYPimage. This factor may sometimes make accurate perioperative identification of fresh infarct difficult, but the application of multiple views, or subtraction imaging, or both techniques usu-

ally clarifies the diagnostic dilemma. Bonte and colleagues [64]have outlined criteria for the characterization of the extent of positivity of pyrophosphate images, and have discussed the difficulty of interpreting the diffusely positive pyrophosphate scan. In 1976, Platt and associates [65] showed that 31% of patients undergoing CABG operation had 99mTc-PYPscintigraphic evidence of perioperative MI when imaged 3 to 5 days postoperatively. They later found that by altering both surgical technique and method of myocardial protection, this incidence could be lowered to 14%. In our recent experience at the University of Florida, the latter figure is slightly higher than the incidence of scintigraphic perioperative MI in over 100 CABG patients studied preoperatively and postoperatively. An example of a positive postoperative 99mTc-PYPscintigram is shown in Figure 5. Although pathological verification of a strongly positive infarct image has been uncommon in reported surgical series, a positive scan in the coronary care unit population is accurate in more than 90% of ECGdocumented transmural infarcts [66]. Increased myocardial uptake of 99"Tc-PYP may also be noted in conditions unrelated to acute myocardial necrosis. Examples of these "false positives" include remote MI, ventricular aneurysm, cardioversion, bacterial endocarditis, cardiomyopathy, and certain lung and breast tumors. Another as yet undetermined question is whether the 99mTc-PYPscan can be positive in severe but reversible myocardial ischemia. Since as many as 30% of patients in reported surgical series have abnormal 99"Tc-PYP scintigrams preoperatively, a comparison of preoperative and postoperative scintigrams is necessary before perioperative MI can be accurately diagnosed on the basis of "hot spot" imaging (671. In cases of well-defined or localized postoperative uptake of radionuclide without similar uptake in intensity or location preoperatively, perioperative MI seems likely [59, 601. The new onset of diffuse uptake postoperatively is suggestive but not diagnostic of myocardial damage; however, the importance of its presence before operation and its disappearance or persistence after operation has not yet been

217 Collective Review: Roberts: Perioperative Myocardial Infarction

tively have not been determined, but the clinical course of such patients is often uncomplicated [59, 691. We have shown that when the only evidence for perioperative MI is a positive %"TcPYP scintigram, there is no related depression of LVEF in the early or late postoperative period 1521.

Myocardial Perfusion Imaging and Coronary Artery Bypass Graft Flow Myocardial perfusion imaging or "cold spot" imaging has been used with increasing frequency in the evaluation of patients with ischemic heart disease. The radionuclide thallium 201 has become the agent of choice for perfusion images. Its biological properties are similar to those of potassium over a wide physiological range of myocardial blood flow, and its uptake is proportional to such flow [70]. Recent technical advances that allow tomographic imaging with O ' 1T1 or positron emission imaging with nitrogen 13-labeled ammonia promise more precise information on regional perfusion [71]. "Cold spot" imaging with "' T1 may be performed at rest or after exercise. Comparison of Fig 5 . Example of a positive myocardial infarct scintigram exercise and redistribution images following exin a patient undergoing coronay a r t e y bypass grafting. (M = external skin marker; L = liver; K = kidney; ANT ercise is a sensitive means of detecting myocar= anterior; LAO = left anterior oblique projection.) dial ischemia [72]. Coronary artery bypass grafting should increase nutrient coronary blood flow, and 'OIT1 perfusion imaging offers a noninclarified [68]. In addition, the lack of sensitivity vasive technique for assessing the results of the of 99"Tc-PYP scintigraphy in the diagnosis of operation. Thallium 201 rest and exercise imaging may subendocardial infarction, which is often characterized by diffuse patchy radiopharmaceutical be very helpful in certain patients who have uptake, has been disappointing. In this situa- moderate coronary arterial obstructions upon tion, the myocardial scan is approximately 65% angiography and whose symptomatology is accurate in detecting a fresh infarct that has marginal. In these instances, exercise-related been documented by the ECG and serum isoen- ischemia or perfusion defects may argue for zyme determinations [66]. This observation has CABG operation. Thallium 201 scintigraphy also considerable clinical importance, since a large permits an objective evaluation of myocardial number of perioperative infarcts are suben- perfusion after revascularization. Since symptomatic improvement following operation may docardial. Myocardial infarct imaging clearly yields a result from a placebo effect, perioperative MI higher incidence of perioperative MI than that or coronary denervation, a noninvasive means indicated by the ECG alone [65,69]. In addition, of assessing changes in myocardial blood flow the concordant use of MI scintigraphy and anal- and graft patency would be useful. Cardiac ysis of serum levels of CK-MB may improve the catheterization combined with coronary angiogdiagnostic accuracy for perioperative MI [57, raphy is the most reliable way to determine 591. The immediate and long-term effects of graft patency, but the invasiveness and inherent new positive scintigrams developing postopera- risk of this technique prohibit serial studies in

218 The Annals of Thoracic Surgery Vol 35 No 2 February 1983

many patients. More recently, sophisticated computed axial tomography has been used to evaluate CABG patency [73], and graft flow hiis been estimated using videodensitometric techniques [74]. Intraoperative Doppler flow studies may provide useful information concerning the physiological consequences of patterns of coronary blood flow [75]. These newer methods are worthy of continued clinical trials. At present, the relationship between changes in myocardial perfusion, perioperative MI, and symptomatic relief related to CABG operation is not necessarily an obvious one. Although between 85 and 90% of saphenous vein bypass grafts should be patent angiographically one year after operation, the incidence of perioperative MI may vary from 2 to 30%. DeLuzio and colleagues [76] reported relief of angina in 5 patients who sustained asymptomatic perioperative MIS in which all bypass grafts were 0-1: cluded. Benchimol and associates [77] also reported the cases of 12 patients in whom all grafts had become occluded; symptomatic improvement was observed in each patient postoperatively, and perioperative MI could be identified in only 4. Some authors have suggested that perioperit tive MI is associated with a high incidence of graft closure [ a ] , while others have thought that patients with perioperative MI have an equal chance of having the graft supplying the area of infarction open or occluded [78].In a recent prospective study, approximately 20% of patients had early postoperative graft angiograms that showed at least one graft occluded but no evidence of transmural MI [79]. One could speculate that in some patients, collateral coronary blood flow is likely to be well developed in the distribution of a critically stenosed coronary artery, thereby protecting the myocardium from necrosis due to a graft occlusion. However, the functional importance of the coronary collateral circulation remains uncertain. Bulkley and Hutchins (451 have shown that myocardial necrosis in the distribution of widely patent coronary bypass grafts occurred in 82,k of the patients studied in their institution. This surprising observation has directed attention to the concept of reperfusion injury following a period of global myocardial ischemia.

Fig 6 . Perfusion defects during exercise and with redistribution after exercise, visualized using thallium 201 radionuclide imaging.

The efficacy of 201T1perfusion imaging in the evaluation of CABG surgery has also been studied. Ritchie and colleagues [80] have found that patients with no new perfusion defects during rest and exercise postoperatively have a graft patency approaching 86%. Conversely, patients with new perfusion defects at rest or developing upon exercise have a diminished graft patency that approaches 50% [72, 801. Early reports suggest that improvement in myocardial perfusion occurs in the majority of patients after CABG operation. An example of "IT1 scintigraphy visualizing regional perfusion abnormalities is shown in Figure 6. Further studies are under way to determine if computerized tomographic 201T1images enable making a more precise assessment of myocardial perfusion. In addition, the relationship between changes in myocardial perfusion and associated LV wall motion before and after CABG operation needs to be clarified [Sl]. Radionuclide Assessment of Left Ventricular Performance in CABG Surgery Radionuclide ventriculography allows the noninvasive determination of global ejection fraction (EF), LV volume and regional wall motion at rest and during exercise [6]. A computerbased time-activity curve is generated, and ventricular contractions may be observed in a

219 Collective Review: Roberts: Perioperative Myocardial Infarction

/

NL

ABN

Fig 7. Radionuclide ventriculogram in left anterior oblique and right anterior oblique projections. The outlines of the left ventricle in end-diastole and end-systole areshown. (NL = normal; ABN = abnormal; RV = right ventricle; LV = left ventricle.) (Reproduced with permission of the publisher from Roberts A], Spies S M , Meyers S N , et al: Early and long-term improvement in left ventricular performance following coronary bypass surgery. Surgery 88:467, 1980.)

Fig 8. Usefulness of serial radionuclide ventriculography in demonstrating perioperative changes in left ventricular performance. (Reproduced with permission of the publisher from Roberts A], Lichtenthal PR, Spies S M , et al: Chapter 4. In Moran J M , Michaelis LL (eds): Surgery for the Complications of Myocardial Infarction. New York, Grune 6 Stratton, 1980,pp 67-92.)

( 801

I

GROUP I L 60MIN.I I

I

GROUP It (61-90MIN.) I

t

1

I

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video format. A radionuclide ventriculogram is shown in Figure 7. The correlation between contrast ventriculography and radionuclide ventriculography has been strong [6, 531. We have shown that the noninvasive radionuclide technique can be performed in the early postoperative period [31, 331. Such studies can accurately assess changes in LV performance related to CABG operation [82] (Fig 8). Most earlier reports suggest that global resting EF is unchanged after CABG operation both one week and several months postoperatively [83, 841. More recently, we showed that resting radionuclide-determined EF is increased above preoperative levels one week after CABG operation and that this improvement

GROUP III

( >90MIN.) I

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220 The Annals of Thoracic Surgery Vol 35 No 2 February 1983

is maintained eight months later [53, 821. We observed an additional postoperative increase in EF with exercise [82]. In spite of these observations, we were surprised to find that approximately 90% of CABG patients have an immediate depression in EF when studied in the intensive care unit using a portable gamma camera two hours postoperatively [31, 331. Also noted by other investigators [85], this condition is transient and usually associated with a stable clinical course. It is our impression that the more recently observed increase in LV perfosmance after CABG operation is not artifactual and is related to improved patient selection, perioperative patient management, and intraoperative myocardial protection [53]. Spotnitz and colleagues [86] and Matsumoto and associates [87l have applied the technique of echocardiography to the study of changes in diastolic compliance and LV performance. This method has been used extensively in cardiology, and may offer surgeons information on ventricular dimensions. Echocardiography avoids radiation hazards and may eventually prove to be most sensitive to changes in regional myocardial wall motion. At the University of Florida, we have begun to compare the relative effectiveness of radionuclide ventriculography and two-dimensional echocardiography in determining LV performance in the perioperative period. The importance of documenting changes in LV performance at rest and during exercise has been cited for patients with coronary artery disease [6]. The adequacy of myocardial revascularization may be similarly evaluated in this fashion (84, 881. Our clinical experience reveals that eight months postoperatively, exerciseinduced EF is increased markedly from resting values [82], a finding uncharacteristic of severe coronary artery disease treated medically (61.

Clinical Factors Associated with Perioperative Myocardial Infarction Although the diagnosis of perioperative MI i s often unclear, some general associations can be made between the preoperative evaluation, perioperative events, and subsequent myocardial damage. The severity of preoperative myocardial ischemia appears to be related to the de-

velopment of perioperative MI [89]. Similarly, the risk of perioperative MI is increased in the presence of severe diffuse multiple vessel coronary artery disease [89-911. Patients with diffuse disease often require longer periods of CPB, or aortic cross-clamping, or both, and operating on them may be technically difficult. In addition, it may not be possible to bypass some coronary obstructions in these patients, and this results in incomplete revascularization and increased perioperative MI. Another factor believed to be related to perioperative MI is the duration of aortic cross-clamping [92], although some investigators would disagree with this observation [41, 681. In general, we believe that the longer the aortic cross-clamp time, the greater the potential for perioperative myocardial damage. Furthermore, the longer the crossclamp time (greater than 60 minutes), the more important the method and application of myocardial protection. Our initial experience with cold blood potassium cardioplegia suggests that this method may be advantageous when longer periods of cross-clamping are needed [93]. At present, the superior method of myocardial protection during aortic crossclamping is highly debatable, but most surgeons would agree that hypothermic potassium cardioplegia has been associated with a decreased incidence of perioperative MI. A related aspect of intraoperative myocardial protection is concern over injury occurring during the initial reperfusion period after continuous aortic cross-clamping. Although this is still under investigation, some researchers have suggested that control of perfusion and flow, calcium ion and pH levels, and other variables during early reperfusion may ultimately decrease myocardial damage [a]. Other factors that may be related to increased perioperative MI include the localized snaring or temporary clamping of coronary arteries [35, 551, prolonged CPB [94], and elevated preoperative LV end-diastolic pressure (951. Patients with left main coronary disease or depressed preoperative EF have also been cited as more likely to develop perioperative MI [95]. Endarterectomy and intramyocardial dissection for buried coronary arteries probably increase the likelihood of perioperative MI [96]. Technical complications related to im-

221 Collective Review: Roberts: Perioperative Myocardial Infarction

CABG operation [52]. We found that only the presence of low cardiac output syndrome immediately after operation correlated with a decreased postoperative EF one week after myocardial revascularization. Moreover, patients with new Q waves showed no increase in postoperative EF, patients with abnormally elevated serum CK-MB values showed only a slight increase in EF, and patients with a positive 99mTcPYP scan showed increased postoperative EF compared with preoperative values. These obPrognosis for Perioperative servations have greater importance when comMyocardial Infarction pared with the usual pattern after “uncomThe mortality associated with perioperative MI plicated” CABG operation [53]. when damage is identified by the sensitive techThe long-term prognosis in patients who niques described in this article is, in our experi- have incurred perioperative MI has also been ence, considerably lower than the current 15% studied. Several groups have observed no detriincidence for acute MI treated at many coronary mental effect on survival [98]; but one recent care units. Left ventricular pump failure second- report documented a decrease in long-term surary to massive subendocardial necrosis remains vival [99]. Postoperative catheterization studies the most common cause of perioperative death have shown that from 1 to 5 years postoperain patients undergoing technically successful tively, LV performance was often adversely afmyocardial revascularization. fected when specific perioperative QRS changes There is considerable uncertainty regarding were present immediately after operation [48] the immediate and long-term prognosis for sur- and was sometimes decreased when postopvivors of perioperative MI. Some investigators erative serum CK-MB level was abnormally think that the immediate postoperative recov- elevated [47]. Conversely, Codd and co-workers ery after perioperative MI is usually benign [59, [1001 have performed a matched-pair analysis of 691 while others have shown an increased patients with and without perioperative MI and perioperative mortality compared with patients have found no differences in subsequent LV who have no perioperative MI [94] or an in- performance. Our experience with eight-month creased incidence of subsequent congestive postoperative noninvasive radionuclide assessheart failure [91]. Our explanation of why ment of patients with postoperative MI after perioperative MI is frequently associated with a CABG operation revealed that resting EF did ”small” infarct and an uncomplicated postop- not significantly decrease from preoperative erative course includes the following: (1) myo- levels. However, patients with perioperative MI cardial hypothermia is present when damage is were found to have a markedly depressed reoccurring or evolving, thus decreasing subse- sponse to exercise, compared with patients who quent infarct size; [2] general anesthesia alters did not have perioperative MI and who were the reactivity of the central nervous system and studied at the same interval postoperatively sympathoadrenal responses, also affecting in- [52]. Further research is needed to define more farct size; (3) myocardial perfusion from patent clearly the hemodynamic importance of peribypass grafts may limit the extent of evolving operative MI. Fortunately, newer perioperative myocardial necrosis in some circumstances; and techniques are lowering the incidence of this (4) extensive mediastinal and intercoronary col- event. lateral circulation provides some protection during ischemic periods. Conclusion We have analyzed the relationship between In this review, we have attempted to show how several criteria used to identify perioperative MI various factors influence the occurrence of and perioperative LV performance related to perioperative myocardial damage, including paproper construction of proximal or distal coronary artery anastomoses may cause perioperative MI, and inadequate orientation of the bypass grafts as they course over the epicardial surface of the heart may lead to kinking and subsequent early graft closure [97]. Sequential bypass grafting must be done extremely carefully, since proximal malconstruction jeopardizes the distal anastomosis and may thus increase the likelihood of perioperative MI.

222 The Annals of Thoracic Surgery Vol 35 No 2 February 1983

tient selection, anesthetic techniques, newer methods of myocardial protection, a n d surgical maneuvers. The diagnosis of perioperative MI is sometimes difficult, a n d we have evaluated the accuracy a s well a s the limitations of current diagnostic techniques. Such diagnostic aids as the ECG, serum enzyme determinations, hemodynamic profiling, echocardiography, a n d radiopharmaceutical methods have been cited as useful in the analysis of surgical results. The cardiac surgical team has reached a level of performance that demands low mortality and morbidity. Future advances will probably involve better means of identifying and quantifying perioperative myocardial ischemia or necrosis, or both. Equipped with such knowledge, surgeons can apply alternative methods to reduce any amount of myocardial damage resulting

from the performance of CABG operations. Such efforts should be judiciously investigated and critically analyzed. With this approach, the immediate a n d long-term functional results after CABG operation will continue to improve. The author would like to acknowledge the support and collaboration of the following associates: John W. Moran, M.D., John H. Sanders, M.D., Lawrence L. Michaelis, M.D., Valavaneur A. Subramanian, M.D., William A. Gay, M.D., Daniel G. Knauf, M.D., Richard S. Faro, M.D., and James A. Alexander, M.D.

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223 Collective Review: Roberts: Perioperative Myocardial Infarction

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-

during coronary operations. Ann Thorac Surg 21:215, 1976 90. Langou RA, Wiles JC, Cohen LS: Coronary surgery for unstable angina pectoris: incidence and mortality of perioperative myocardial infarction. Br Heart J 40:767, 1978 91. Brewer DL, Bilbro RH, Bartel AG: Myocardial infarction as a complication of coronary bypass surgery. Circulation 4758, 1973 92. Righetti A, Crawford MH, ORourke RA, et al: Detection of perioperative myocardial damage after coronary artery bypass graft surgery. Circulation 55:173, 1977 93. Roberts AJ, Moran JM, Sanders JH, et al: Clinical evaluation of the relative effectiveness of multidose crystalloid and cold blood potassium cardioplegia in coronary artery bypass graft surgery: a nonrandomized matched-pair analysis. Ann Thorac Surg 33:421, 1982 94. Langou RA, Wiles JC, Peduzzi PN, et al: Incidence and mortality of perioperative myocardial infarction in patients undergoing coronary artery bypass grafting. Circulation 56:Suppl 254, 1977 95. Baur HR, Peterson TA, Arnar 0, et al: Predictors of perioperative myocardial infarction in coronary artery operation. Ann Thorac Surg 31:36, 1981 96. Kamath ML, Schmidt DH, Pedraya PM, et al: Patency and flow response in endarterectomized coronary arteries. Ann Thorac Surg 31:28, 1980 97. Hutchins GM, Bulkley BH: Mechanism of occlusion of saphenous vein-coronary artery "jump" grafts. J Thorac Cardiovasc Surg 73:660, 1977 98. Bonchek LI, Rahimtoola SH, Chaitman BR, et al: Vein graft occlusion: immediate and late consequences and therapeutic implications. Circulation 49:Suppl2:84, 1974 99. Oberman A, Cutter G, Kouchoukos N, et a1 Survival following perioperative myocardial infarction. Circulation 62:Suppl3:94, 1980 100. Codd JE, Wiens RD, Kaiser GC, et al: Late sequelae of perioperative myocardial infarction. Ann Thorac Surg 26:208, 1978