Andrew J. Kemper

Perioperative myocardial infarction after coronary artery bypass surgery. Clinical significance and approach to risk stratification.

The clinical significance of perioperative myocardial infarction (MI) after coronary artery bypass surgery is not known. Therefore, strategies for the risk stratification of these patients do not exist. This study was undertaken to define the effect of perioperative MI on prognosis after discharge from the hospital and to develop an approach to the risk stratification of these patients. Fifty-nine patients with and 115 patients without perioperative MI were observed for 30 months for the development of cardiac events (death, nonfatal MI, and admission to hospital for unstable angina or congestive heart failure). Patients with perioperative MI were significantly more likely than patients without to have a cardiac event (31% versus 12%, p less than 0.01) and multiple events (19% versus 1%, p less than 0.001). Cox regression analysis identified two independent predictors of cardiac events other than perioperative MI (relative risk, 2.7): inadequate revascularization (relative risk, 3.5) and depressed (less than 40%) postoperative ejection fraction (EF) (relative risk, 2.1). Event-free survival rate of patients with perioperative MI varied markedly depending on the number of other negative prognostic variables present. Patients with perioperative MI who were adequately revascularized and had a postoperative EF greater than 40% had an event-free survival rate similar to patients without a perioperative MI (92% versus 87%, p = NS). Patients with perioperative MI who were inadequately revascularized and had depressed postoperative EF had an event-free survival rate of 13% (p less than 0.001 versus all other subsets). Event-free survival rate was intermediate (68%) in patients with perioperative MI and with only one of the other two variables (p less than 0.001 versus other subsets). In conclusion, perioperative MI adversely affects prognosis. Patients can be stratified into low, high, and intermediate risk subsets based on a simple assessment of the adequacy of revascularization and a determination of residual left ventricular function.

Acute reduction in functional infarct expansion with late coronary reperfusion: Assessment with quantitative two-dimensional echocardiography☆

Reperfusion performed too late to salvage myocardium decreases chronic infarct expansion in experimental animals. However, the acute effects of delayed reperfusion are not known. Twenty-two dogs underwent 3 (n = 8), 4 (n = 8) or 6 h (n = 6) of circumflex artery occlusion followed by 3 h of reperfusion. Effects of reperfusion on diastolic expansion were assessed in two ways: 1) change in mean radius of curvature of the infarct segment, and 2) change in the ratio of the length of the diameter from the center of the infarct zone to the opposite wall (septal-lateral diameter) to the length of the diameter perpendicular to this (anteroposterior diameter). Effects on systolic expansion were examined with quantitative two-dimensional echocardiographic systolic thickening analysis. Delayed reperfusion produced an immediate decrease in diastolic infarct expansion. The ratio of septal-lateral/anteroposterior diameters, which had increased with occlusion from a preocclusion baseline of 0.98 +/- 0.06 to 1.13 +/- 0.08 (p less than 0.001), decreased with reperfusion to 1.02 +/- 0.07 at 15 min and 1.03 +/- 0.08 at 3 h of reperfusion (p = 0.001). This was due solely to a decrease in the septal-lateral diameter. The radius of curvature of the infarcted segment increased from 2.1 +/- 0.5 cm before reperfusion to 2.74 +/- 0.8 cm at 15 min and 2.6 +/- 0.85 cm at 3 h of reperfusion (p = 0.009). This occurred despite a significant (13.6%) decline in end-diastolic cavity area and is compatible with flattening of the reperfused infarct region. Systolic infarct expansion also improved slightly.(ABSTRACT TRUNCATED AT 250 WORDS)

Contrast echocardiographic estimation of regional myocardial blood flow after acute coronary occlusion.

Contrast echocardiography can predict pathologic area at risk during acute coronary occlusion. In this study we evaluated (1) whether the intensity and timing of contrast appearance in ischemic regions can provide a quantitative measure of residual myocardial perfusion, and (2) whether changes in these parameters observed after serial injections reflect changes in blood flow to acutely ischemic tissue. Supra-aortic hydrogen peroxide contrast echocardiography was performed in 12 consecutive dogs at 1, 20, and 120 min after acute circumflex coronary occlusion. Contrast enhancement was determined qualitatively with a segmental four-point scoring system based on the appearance time and peak perceived intensity of contrast enhancement and quantitatively with a computer algorithm designed to reflect these parameters. Comparison was made in each segment to concomitant radioactive microsphere blood flow. Qualitative scoring related systematically to normalized segmental blood flow (3+ = 93%; 2+ = 61%; 1+ = 32%; 0 = 18%; p less than .01 for each vs adjacent value), as did quantitative analysis including all segments (r = .78; p less than .01) and isolated to the ischemic region (flow = 1.13 intensity change +6.8%; r = .83, p less than .001). Changes in microsphere flow in ischemic regions between sequential observations were correlated with changes in qualitative score (r = .88, p less than .001) and results of quantitative analysis (r = 0.70, p less than .01). The amount of contrast enhancement can provide quantitative information about residual myocardial blood flow in ischemic regions and can also be used to track changing patterns of flow in vivo after acute coronary occlusion.

In vivo prediction of the transmural extent of experimental acute myocardial infarction using contrast echocardiography

Acute myocardial infarction progresses radially from endocardium to epicardium within the ischemic area. The amount of progression is highly variable, but depends largely on the transmural distribution of myocardial blood flow. Recent contrast echocardiographic observations indicate that slowly appearing low levels of contrast enhancement are often seen in the ischemic region, particularly in the epicardial level, and that ischemic regions which show these low levels of contrast have significantly more blood flow than those that do not. This study was designed to determine whether the transmural distribution of this delayed contrast enhancement can sufficiently discriminate between regions of high and low flow to serve as an in vivo predictor of the transmural extent of acute infarction. Twenty-four dogs had acute circumflex coronary ligation which was maintained for 6 hours. Contrast echocardiographic studies were performed at the level of the mitral chordae 2 hours after occlusion using a dilute hydrogen peroxide and blood solution as a contrast agent. Comparison was made with the pathologic infarct measured by triphenyltetrazolium chloride staining. The mean transmural extent of infarction ranged from 0 to 89% and was predicted in vivo by the transmural extent of the delayed contrast defect (r = 0.92; infarction [percent transmural] = 0.74 contrast [percent transmural] + 11%; SEE = 10%). Reproducibility for the transmural extent of delayed contrast defects was good (r = 0.89 to 0.98.) These data further support the concept that the transmural distribution of delayed contrast enhancement parallels blood flow and indicate that the mean transmural extent of acute infarction can be predicted in vivo 2 hours after coronary occlusion from the residual contrast defect.

Non-Q wave perioperative myocardial infarction: assessment of the incidence and severity of regional dysfunction with quantitative two-dimensional echocardiography.

Since the widespread use of hypothermic potassium cardioplegia began, marked reductions in perioperative mortality and the rate of Q wave-associated myocardial infarctions have been noted. No study to date has evaluated whether there has been an equally dramatic improvement in the incidence of postoperative myocardial infarctions unassociated with Q wave development. We used a previously validated quantitative two-dimensional echocardiographic analytic algorithm to determine the incidence and severity of regional wall motion abnormalities (RWMAs) and first-pass radionuclide ventriculography to assess deterioration in global left ventricular function in the four following groups of patients (total n = 65): (1) those with peak postoperative creatine kinase (CK)-MB levels equal to or less than the mean value for patients undergoing coronary artery bypass surgery at our institution (n = 10), (2) those with CK-MB levels between the mean and 1 SD above the mean (n = 10), (3) those with peak CK-MB levels higher than 1 SD above the mean (n = 25), and (4) those with new pathologic Q waves on the postoperative electrocardiogram (n = 20). All patients had electrocardiograms without pathologic Q waves and normal wall motion and ejection fraction by contrast ventriculography before surgery. The incidence of postoperative RWMA by two-dimensional echocardiography for groups 1 through 4 was 0%, 20%, 55%, and 89%, respectively. Percent of abnormal left ventricular segments, wall motion scores, and the deterioration in left ventricular ejection fraction as assessed by radionuclide ventriculography were similar for patients with new RWMAs whether or not new Q waves developed (p = NS for all).(ABSTRACT TRUNCATED AT 250 WORDS)

Intraaortic balloon counterpulsation as a temporary support measure in decompensated critical aortic stenosis.

Intraaortic balloon counterpulsation was instituted in two adult patients whose condition was rapidly deteriorating because of critical decompensated valvular aortic stenosis. The acute hemodynamic effect of counterpulsation in these patients was compared with the effect of counterpulsation in three control patients with unstable angina and no aortic valve disease. Augmentation of aortic diastolic pressure was similar in both groups; however, in contrast to the patients with unstable angina, the patients with aortic stenosis had no decrease in left ventricular systolic pressure. Counterpulsation resulted in an increase in the transvalvular pressure gradient, which was associated with a slight increase in stroke volume. In both patients with aortic stenosis, the institution of counterpulsation resulted in marked clinical improvement, which facilitated successful valve replacement surgery. The benefit from counterpulsation in critically decompensated aortic stenosis appears to be derived almost entirely from augmentation of the diastolic coronary filling gradient. The improvement that results from counterpulsation suggests that ischemia is the major cause of decompensation.

Early loss of postextrasystolic potentiation in acutely ischemic myocardium: evaluation by contrast two-dimensional echocardiography.

Studies in animals with acutely ischemic hearts have suggested that postextrasystolic potentiation (PESP) may predict the viability of dysfunctional myocardium. Most of these data have been obtained with sonomicrometers and therefore the presence and extent of PESP throughout the entire region at risk has not been defined. In this study we used contrast two-dimensional echocardiography (2DE) to define region at risk in vivo, and then with quantitative 2DE we examined the proportion of the region at risk that demonstrated PESP, the degree of the potentiation, and the time course of this response. The region at risk was divided into a central (inner 50%) and two peripheral (25% each) ischemic zones. Adjacent contrast-enhanced myocardium was divided into near and far border zones that were equal in size to the adjacent peripheral ischemic zone. Systolic thickening was analyzed within each zone along multiple radii at 5, 30, and 120 min after coronary occlusion. PESP was absent in the central ischemic zone at all three times. In the peripheral ischemic zone at 5 min, a small amount of PESP was detected (-4.1% vs + 3.1% for nonpotentiated and potentiated thickening, respectively; p less than .01). At 30 min after occlusion, no potentiation was seen in the region at risk and PESP was confined to the contrast-enhanced near and far border zones. These findings persisted at 120 min. These data indicate that the response to PESP is localized to perfused myocardium by 30 min after acute occlusion. PESP is therefore of limited value in predicting the presence of ischemic, potentially viable myocardium early in the course of acute infarction.

Topographic Correspondence of Contrast Echocardiographic Perfusion Mapping and Myocardial Infarct Extent After Varying Durations of Coronary Occlusion

After acute coronary occlusion, the extent of dysfunction exceeds the extent of infarction by a variable amount. Contrast echocardiography has been shown to be a good predictor of the extent of acute infarction after permanent occlusion. We used hydrogen peroxide contrast echocardiography to study the temporal and topographic relationship between contrast enhancement and tissue viability during acute myocardial infarction in 32 dogs undergoing 1, 2, 3, or 4 hours of circumflex occlusion before reperfusion. To account for changes in collateral blood flow, contrast studies were performed by aortic root injection immediately before reperfusion. The area, circumference, and transmural extent of the region at risk in vivo by contrast echocardiography were statistically unchanged regardless of the duration of occlusion before reperfusion. Echo contrast defect analysis of the risk region predicted the area, circumference, and transmural extent of infarcts reperfused at 2 or more hours (r = 0.81, 0.84, 0.71, respectively). For the 1-hour occlusion group, contrast defect analysis predicted the circumference at risk but markedly overestimated the area and transmural extent of infarction. These data indicate that the circumferential extent of infarction can be identified by contrast echo and is fixed by 1 hour of occlusion. Infarction progression transmurally within the circumferential boundaries had nearly reached the transmural contrast extent by 2 hours of occlusion in this model. Assuming the development of a similar high contrast agent safe for human injection, aortic root contrast echocardiography could be useful to predict myocardium at risk of infarction early after occlusion. Late after occlusion it could be of value to predict the presence of still viable myocardial layers within the dysfunctional infarct region.

The interval ejection fraction: a cineangiographic and radionuclide study.

To evaluate the clinical usefulness of the first-third ejection fraction (1/3 EF) for detecting patients with coronary artery disease (CAD), resting contrast ventriculography and first-pass radionuclide angiography with a high-count-rate, multicrystal camera system were performed in 47 subjects: 22 normal controls (group 1) and 25 patients with clinically stable angina pectoris and severe CAD (mean 2.3 vessels) without (group 2, n = 12) and with (group 3, n = 13) resting wall motion abnormalities. By contrast angiography, only group 3 had depressed global EF or 1/3 EF compared with control (global EF: group 1, 0.71 ± 0.09; group 2, 0.67 i 0.09 [NS]; group 3, 0.49 ± 0.05 [p < 0.01 vs groups 1 and 2]; 1/3 EF: group 1, 0.29 ± 0.06; group 2, 0.28 i 0.05 [NS]; group 3, 0.22 ± 0.05 [p < 0.01 vs groups 1 and 2]). Whereas 11 of25 CAD patients had global EF outside the normal range, only two of 25 had depressed 1/3 EF. Both had left ventricular asynergy and a depressed global EF. Studies performed using first-pass radionuclide angiography revealed similar results, i.e., only four of 25 CAD patients, all with left ventricular asynergy and depressed global EF, had depressed 1/3 EF values. A wide range of 1/3 EF values was found in normal subjects by both techniques. Thus, the ejection fraction during the first third of systole at rest is of limited value for detecting patients with CAD.

Quantifying Changes in Regional Myocardial Perfusion with Aortic Contrast Echocardiography

We developed a technique to assess regional myocardial perfusion by quantifying echocardiographic myocardial contrast appearance and intensity after aortic root injection of an agitated diatrizoate meglumine solution. The technique was validated by comparing digitized echocardiographic contrast parameters to regional perfusion in the circumflex bed determined by calibrated Doppler flow probe and antemortem monastral blue staining. Regional perfusion was altered by circumflex stenosis, occlusion, and reactive hyperemia. Contrast effects were measured in an initial subset of six dogs by peak intensity change, time to peak intensity, maximal rate of intensity rise, and mean intensity change integrated over 1, 2, or 3 seconds after contrast appearance (MI1, MI2, MI3). MI2 and MI3 best predicted regional perfusion (r = 0.93, standard error of the estimate [SEE] 0.38 ml/gm/min for each). These findings were confirmed in a second subset of six dogs (r = 0.84, SEE = 0.70 ml/gm/min). Although there was a relatively broad standard error for the prediction of absolute perfusion for the pooled data, for individual dogs data were internally consistent so that each had r greater than 0.88 for its varied flow states. The hyperemic ratio calculated by contrast echocardiography correlated well with the Doppler value (r = 0.85). Observer and study-to-study predictive variabilities were small (SEE 0.19 to 0.32 ml/gm/min). No alterations were seen in hemodynamics or reactive hyperemia after 25 consecutive injections over a 90-minute period. Contrast echocardiography with aortic root contrast injection tracks changes in regional blood flow. This approach can assess regional coronary reserve and detect changes in regional myocardial perfusion during acute ischemia and drug intervention.