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Differences in left ventricular function between anterior and inferior myocardial infarction of equivalent enzymatic size
Internarional
Journal of Cardiology,
155
17 (1987) 155-168
Elsevier
IJC 00597
Differences in left ventricular function between anterior and inferior myocardial infarction of equivalent enzymatic size Mark E. Hands, Vince Antico, Peter L. Thompson, James S. Robinson, Brian L. Lloyd,
Joseph Hung,
Department of Cardiovascular Medicine, Sir Charles Gairdner Hospital, Queen Elizabeth II Medical Centre, Nedlands, Western Australia (Received
31 March
1987; accepted
18 May 1987)
Hands ME, Antic0 V, Thompson PL, Hung J, Robinson JS, Lloyd BL. Differences in left ventricular function between anterior and inferior myocardial infarction of equivalent
enzymatic
size. Int J Cardiol
1987;17:155-168.
The reasons for the poorer prognosis of anterior versus inferior myocardial infarction of equivalent enzymatic size remain uncertain. We investigated whether there are differences in left ventricuhu function between patients with anterior and inferior infarctions of equivalent enzymatic size to account for their differing outcomes. Clinical, serum enzyme, and electrocardiographic data were prospectively recorded in a consecutive series of patients less than 70 years of age with their first myocardial infarction. At 29 f 6 days following infarction, ejection fraction and left ventricular wall motion were assessed by gated heart scintigraphy and functional capacity by treadmill exercise testing in 19 patients with anterior and in 23 patients with inferior myocardial infarction. Peak creatine kiuase and QRS scores were used to estimate total infarct size and left ventricular infarct size respectively. The anterior infarcts were of similar size to the inferior infarcts as determined by peak creatine kinase (1444 [mean] f 1161 [SD] U/L versus 1484 [mean] f 1182 [SD] U/L, respectively, P = 0.91) and peak aspartate transaminases (174 f 112 U/L versus 164 f 102 U/L, P = 0.78). The anterior myocardial infarct group had a greater percentage of the left ventricle infarcted on QRS scoring tbau the inferior infarct group (25.9 f 14.4% versus 11.1 f 6.0% respectively, P = 0.0004), lower global left ventricular ejection fraction (45.8 f 16% versus 54.6 f 9.2%, P = 0.04)and greater left ventricular regional wall abnormality. A significant negative correlation
Correspondence to: Dr. Mark E. Hands. Francis Street, Boston, MA 02115, U.S.A.
0167-5273/87/$03.50
Cardiovascular
0 1987 Elsevier Science Publishers
Division,
Brigham
B.V. (Biomedical
and Women’s
Division)
Hospital,
75
156
existed between left ventricular ejection fraction and peak creatine kinase for both groups, but was more marked with anterior infarction (r = - 0.78, P < 0.01) compared with inferior infarction (r = -0.49, P -c0.05). Exercise-induced ST segment elevation was more frequent in the anterior than the inferior infarct group (59% versus 18%, P -K0.02). However, both infarct locations had similar exercise tolerance, exercise-induced angina and ST segment depression. Despite equivalence of infarct size of the two infarct locations on enzyme testing, anterior infarction was associated with greater abnormality of left ventricular function with lower resting global left ventricular ejection fraction; greater resting left ventricular regional wall abnormality and greater exercise-induced ST segment elevation. These differences probably contribute to the poorer prognosis of patients with anterior infarction compared to those with inferior infarction of equivalent enzymatic size, given the previously well-documented prognostic importance of left ventricular function. Key words:
Infarct
location;
Creatine
kinase;
Left ventricular
function;
QRS score
Introduction Factors influencing the prognosis of patients following myocardial infarction have been the subject of intensive investigation [l-14]. These studies have demonstrated that left ventricular function [l-7], infarct size [2,8-lo], history of previous infarction [4], coronary anatomy [7], and ventricular instability [2] are independent prognostic indicators following myocardial infarction. More recently, the location of myocardial infarction has been identified as an important factor influencing subsequent outcome, with patients with anterior myocardial infarction having a worse prognosis than those with inferior myocardial infarction of equivalent enzymatic size [ll-131. The reasons for this are not clear, given that cardiac enzyme levels reflect the extent of myocardial necrosis [9,10,14-171. However, right ventricle involvement in inferior infarctions has been documented [12,18-21]. Therefore, a possible explanation is that in a proportion of patients with inferior infarction, right ventricular necrosis contributes to the cardiac enzyme level, such that the latter may not accurately reflect the extent of left ventricular damage in this group of patients. Our study sought to evaluate the possibility that left ventricular function differs between anterior and inferior myocardial infarction of equivalent enzymatic size. We prospectively studied patients with anterior and inferior infarctions and the association between infarct site and the extent of left ventricular infarction based on QRS scoring; left ventricular function as assessed by radionuclide scanning; and functional capacity as determined by exercise treadmill testing. In addition, we sought to evaluate the extent of right ventricular involvement in inferior infarction which may account for any differences in left ventricular function between the two infarct locations.
157
Materials and Methods Patient Population Patients less than 70 years of age admitted to the Sir Charles Gairdner Hospital’s coronary care unit between January and September 1984, with definite acute myocardial infarction, were prospectively evaluated. Patients excluded from the study were: (1) those with previous myocardial infarction; (2) those in whom the site of infarction could not be located electrocardiographically, i.e., patients with left bundle branch block or no electrocardiographic changes; (3) those admitted to hospital after 24 hours from the onset of chest pain as their peak creatine kinase may have been missed; (4) those with factors other than myocardial necrosis known to influence peak creatine kinase levels, including thrombolytic therapy, intramuscular injections, direct current cardioversion, and underlying skeletal muscle disorder; (5) those who died or had coronary artery bypass surgery or coronary angioplasty during the first month following myocardial infarction; and (6) those who were considered unavailable for subsequent study because of distant domicile. Forty-two patients were entered into the study, 19 with anterior or anterolateral infarction and 23 with inferior or inferolateral infarction. Recruitment of patients ceased with the introduction of the routine use of intravenous streptokinase for patients with acute infarction in our unit. Clinical Data Clinical, serum enzyme, and electrocardiographic data were recorded during the patient’s hospital stay. Past history of myocardial infarction was documented if there was a history of typical pain supported by typical electrocardiographic or enzyme abnormalities. Clinical right ventricular infarction was diagnosed if the jugular venous pressure was elevated in the setting of myocardial infarction without clinical or radiological evidence of left ventricular failure. Left ventricular failure was defined as persistent basal lung crepitations associated with a third heart sound and/or radiological evidence of left heart failure during the patient’s hospital stay. Conduction disturbances were detected by computerized monitoring of the electrocardiogram and documented by analysis of 24 hours’ stored computer-generated electrocardiograms. During the initial 48 to 72 hours in hospital, the serum creatine kinase and aspartate transaminase were estimated at least twice daily. The peak level was the highest of these readings. The upper limit of normal creatine kinase in our laboratory is 180 international units per litre (U/L) and for aspartate transaminase is 40 U/L. The electrocardiographic site of infarction was assessed from the 12-lead electrocardiograms recorded at least daily for the first three days following admission. Anterior myocardial infarction was defined as the development of new Q waves and/or sequential ST segment elevations or T wave changes in leads Vl through V4.
158
Inferior myocardial infarction was defined as new Q waves and/or sequential ST segment elevations or T wave changes in leads II, III, and aVF. Anterolateral or inferolateral infarction was defined if, in addition, there were new Q waves or sequential ST segment elevations or T wave changes in leads V5, V6, and/or I and aVL. Repeat electrocardiogram for QRS scoring; gated heart scintigraphy for analysis of right and left ventricular function; and symptom-limited exercise treadmill test for assessment of functional capacity were performed at one month post myocardial infarction. These studies were performed within a 24 to 48 hour period of each other. QRS Scoring The electrocardiograms were all recorded on a three-channel Hewlett Packard recorder, with a frequency response of 0.5-110 Hz and speed of 25 mm/set. The 1Zlead electrocardiogram was used to derive a QRS score, based on the modified QRS scoring method by Wagner et al. [22], as an estimate of the size of left ventricular infarction. This 29-point scheme is based upon observed duration of Q and R waves and R/Q and R/S amplitude ratios in the standard 12-lead electrocardiogram (omitting leads III and aVR) in selected patients with initial anterior and inferior infarcts who succumbed as a result of the infarction. In that study, the amount of left ventricular myocardial necrosis was quantitatively assessed at autopsy. The higher the QRS score the greater the amount of left ventricular myocardial necrosis. Our 12-lead electrocardiographic tracings were read independently by two observers. The average of the two QRS scores was used. The percentage of the left ventricle infarcted was determined from previously published regression equations as follows: 96 in anterior
infarction
= 3.6
% in inferior
infarction
= 2.5
x x
QRS score + 3.2 [23] ; QRS score + 2.9 [24].
Radionuclide Studies Equilibrium gated heart scintigraphy was performed following in vitro labeling of autologous red blood cells [25]. Data were collected with a standard portable gamma camera (Technicare Sigma 420) onto a dedicated computer (DEC P.D.P. 11/34). Images were obtained in three views: (1) best septal left anterior oblique with caudal tilt obtained utilizing a 20 slant hole collimator, (2) 30 right anterior oblique, and (3) left lateral. Left and right ventricular ejection fractions were calculated from the left anterior oblique study, utilizing a semi-automatic program [26]. The left ventricular ejection fractions and the left ventricular time activity curve was calculated from multiple
159
regions of interest in the cardiac cycle. Bight ventricular ejection fraction is generated from diastolic and end-systolic regions of interest similar to the method of Maddahi et al. [27]. Data from 20 normal patients had previously documented the normal left ventricular ejection fraction to be 62.5 f 5.3% and the right ventricular ejection fraction 49.4 f 6.1%. Semi-quantitative assessment of regional wall motion was performed while viewing a cinematic display of all three views of the study. The method was adapted from that of Zaret et al. [28]. The left ventricle was divided into 11 equal segments. Anterior or inferior myocardial infarction could each potentially involve six of these segments, with involvement of the apical segment only being potentially common to both. Each segment was given a score according to its motion, i.e., 3 for normal, 2 for mildly hypokinetic, 1 for severely hypokinetic, 0 for akinetic, and -1 for clearly dyskinetic wall motion. Therefore, the lower the score the greater the left ventricular regional wall abnormality. If the left ventricle had entirely normal function, a score of 33 would be recorded. The right ventricle was considered separately as one segment with the same scoring system being applied. All studies were analyzed by the same blinded observer. Exercise Treadmill Testing
Symptom-limited exercise treadmill testing was performed at one month post myocardial infarction using the Naughton-Bake protocol [29]. Included in the recordings were the patient’s exercise tolerance, expressed in metabolic equivalents of oxygen consumptions (METS), presence or absence of chest pain typical of angina and the presence or absence of exercise-induced ST segment depression or elevation. ST segment depression was observed if, during exercise, the ST segment fell 2 1 mm from the resting baseline 80 msec after the J point. ST segment elevation was recorded if the ST segment rose > 1 mm from the resting J point. Analysis of Data
Differences between patient characteristics for the two infarct locations were examined. Discrete variables were tested against the &i-square distributions, with the use of the Yates correction where appropriate. For continuous variables the Student t-test was applied. The non-parametric Spearman rank correlation was utilized to compare the distribution of patients in each subgroup of peak creatine kinase for both infarct locations. A P value of less than 0.05 was considered significant. Results
Both the anterior and inferior infarct groups had similar peak creatine kinase (1444 [mean] + 1161 [SD] U/L versus 1484 [mean] rt 1182 [SD] U/L, respectively, P = 0.91) and similar peak aspartate transaminase (174 + 112 U/L versus 164 k 102 U/L, respectively, P = 0.78) (Table 1). In addition, non-parametric Spearman rank
160 TABLE
1
Characteristics
of patient
population
studied.
Anterior Age (years) Male : female ratio Peak CK (U/L) Peak AST (U/L) Q wave MI (W) RV infarction (%) LV failure (W) 2/3 AV block (W) Beta-blocker (W) Calcium antagonists Nitrates (W) Diuretics (%) Digoxin (W)
(W)
MI n = 19
59.2 + I 3.6 : 1 1444* 1161 174+ 112 13 0 33 5 42 21 36 21
Inferior
MI n = 23
Significance
4.3 35 5 39 21 36 27 9
5
P value
NS NS NS NS NS NS NS NS NS NS NS NS NS
53.4k11.7 4.75 : 1 1484* 1182 164 f 102 65
MI = myocardial infarction; n = number of patients; NS = not significant (P creatine kinase; AST = aspartate transaminase; RV = right ventricular (clinical): AV = atrioventricular; 2 = second degree; 3 = third degree; % percentage.
value > 0.05); CK = LV = left ventricular;
correlation testing indicated that there were no significant differences in the number of patients in the different subgroups of peak creatine kinase (Fig. 1). Patients in the two infarct locations were similar for age, sex, Q-wave infarction, clinical and
cl
o-a
a -
16
16
CAEATINE
Fig. 1. Distribution
of infarct
-
24
24 KINASE
-
32
32 (U/L
INFERIOR
MI
n
= 23
ANTERIOR
MI
n
=
-
40
x
102)
40
-
48
size based on peak creatine kinase (CK) level. MI = myocardial n = number of patients; U/L = units per liter.
48
19
-
56
infarction;
161 TABLE
2
Electrocardiographic
and gated heart scintigraphy Anterior
QRS score (from ECG)
6.3k
LV infarcted (W) (from QRS score) LVEF (%)
MI = myocardial electrocardiograph;
4.0
25.9* 14.4 45.8 f 16
LV segments (with abnormal motion) LV regional wall abnormality score RVEF (S) RV wall motion abnormality (%)
MI n = 19
5.4*
3.4
25.5k 52.5k
7.8 9.3
26
results Inferior
3.3+
MI n = 23
2.4
11.1 & 6.0 54.6 k 9.2 3.8*
Significance
P value
0.008 0.0004 0.04
3.0
0.14
29.3+ 5.9 54.4*11.2
0.09 NS
39
NS
infarction; n = number of patients; NS = not significant (P > 0.05); ECG = LV = left ventricular; RV = right ventricular; EF = ejection fraction; % = percentage.
radiological evidence of left ventricular failure, clinical evidence of right ventricular infarction, conduction disturbances, and prescription of medications that could potentially influence left ventricular function (Table 1). In Table 2 are shown estimates of the left ventricular infarct size based on the 12-lead electrocardiogram at one month post infarction. The anterior infarct group had a significantly greater QRS score than the inferior infarct group (6.3 + 4.0 versus 3.3 k 2.4, P = 0.008). Accordingly, the derived percentage of left ventricle infarcted was significantly greater in the anterior infarct group than the inferior infarct group (25.9 + 14.4% versus 11.1 + 6.0%, P = 0.0004). The results of the gated heart scintigraphy are also displayed in Table 2. The anterior infarct group had significantly lower mean global left ventricular ejection fraction than the inferior group (45.8 k 16% versus 54.6 + 9.4%, P = 0.04). The number of left ventricular segments with abnormal motion in the anterior infarct group tended to be greater than the inferior infarct group, although this did not achieve statistical significance (5.4 + 3.4 versus 3.8 f 3.0, P = 0.14). Estimation of left ventricular regional wall abnormality as described in the methods showed a similar but not significant trend with the anterior infarct group having a lower LV regional wall score of 25.5 &-7.8 as compared with the inferior infarct group score of 29.3 + 5.9 (P = 0.09). Figs. 2 and 3 demonstrate the correlations between left ventricular ejection fraction and peak creatine kinase for the anterior and inferior infarct groups respectively. Inverse correlations are evident for both anterior (r = -0.78) and inferior (r = -0.49) infarction, the correlation being more significant for the anterior than inferior infarct group (P < 0.01 versus P < 0.05, respectively). The graphs illustrate that the larger the infarct the greater the impairment of left ventricular function for anterior infarction compared with inferior infarction of equivalent enzymatic size.
162 ANTERIOR
M
I
loo-
800 60-
=
19
=
-0.78
*
P
<
0.01
0
0 u.
n r
’
w > -1
40-
20-
O-0
8
16
24
CREATINE
Fig. 2. Correlation between left ventricular in anterior myocardial infarction
32
KINASE
40
[ U/L
LA.
66
x 102 I
ejection fraction (LVEF) and peak creatine kinase (CK) levels (MI). n = number of patients; U/L = units per liter. M
INFERIOR
80
48
I
”
=
r
=
x
p
23 -0.49
<
0.05
l
60
w > 40
20
0
I
I
I
8
16 CREATINE
Fig. 3. Correlation between left ventricular in inferior myocardial infarction
I
24
1
32 KINASE
40 [ut
1
48
1
66
x102]
ejection fraction (LVEF) and peak creatine kinase (CK) levels (MI). n = number of patients: U/L = units per liter.
163 TABLE
3
Symptom-limited
exercise treadmill
test (Naughton-Balke
Anterior Exercise workload (METS) Angina ST segment depression ST segment elevation
II = 17
6.5+1.7 29% 41% 59%
MI = myocardial infarction; n = number equivalents of oxygen consumption.
protocol). Inferior
n = 22
7.2+1.8 23% 52% 18% of patients;
NS = not significant
Significance
P value
NS NS NS 0.02
(P > 0.05); METS = metabolic
Right ventricular ejection fraction was similar for both anterior and inferior infarct groups (52.9 + 9.3% versus 54.4 k 11.2%. respectively). However, a greater percentage of patients with inferior infarction had visually observed right ventricular wall motion abnormality than those with anterior infarction (39% versus 26%, respectively), although this difference did not achieve statistical significance (Table 2). Twenty-two of the 23 patients with inferior infarction underwent exercise testing. The remaining patient in this group was excluded due to unstable angina. Two patients in the anterior infarct group were not tested. One of these had unstable angina and the other had a large left ventricular thrombus demonstrated on cross-sectional echocardiography. Both anterior and inferior infarct groups had similar exercise capacities (6.3 k 1.7 METS versus 7.2 f 1.8 METS, respectively, NS) (Table 3). They also had similar frequencies of exercise-induced angina and exercise-induced ST segment depression. Notably, patients with anterior infarction had a significantly greater incidence of exercise-induced ST segment elevation than those with inferior infarction (59% versus 18% respectively, P = 0.02).
Discussion Our results show that there is greater left ventricular involvement and dysfunction in patients with anterior myocardial infarction than in those with inferior myocardial infarction of equivalent enzymatic size. This conclusion is drawn from the results obtained from assessment of (1) left ventricular infarct size by QRS scoring, and (2) left ventricular function by gated heart scintigraphy, utilizing the parameters of global left ventricular ejection fraction and regional wall motion. Given that less left ventricular impairment occurred in patients with inferior infarction than those with anterior infarction of equivalent enzymatic size, we conclude that the enzyme release in the former is not all secondary to left ventricular damage. Previous studies with hemodynamic monitoring [12], thallium201 scintigraphy [18], blood pool imaging [19], and necropsy (201 have suggested the involvement of the right ventricle in inferior myocardial infarction. Therefore, right ventricular necrosis may contribute to enzyme release in some patients with inferior infarction which may explain the differences in left ventricular function between the
164
two infarct locations. Our results are in keeping with this explanation with greater radionuclide right ventricular wall motion abnormality being detected in the inferior infarct group, but are not conclusive. The lack of significant difference in right ventricular function found between our two infarct groups may relate to the lack of specificity of the radionuclide technique used to evaluate right ventricular function. It is well documented that spontaneous early reperfusion in myocardial infarction may significantly contribute to the magnitude of the peak creatine kinase level independent of myocardial necrosis [30]. Therefore, an alternative explanation for our results may be that early spontaneous reperfusion occurs more often in patients with inferior myocardial infarction than those with anterior myocardial infarction. The latter has yet to be established. However, if this postulate were true then indeed greater left ventricular impairment would be expected in anterior infarction compared with inferior infarction of equivalent enzymatic size. In this case, there need not be any difference in right ventricular function to explain the differences in left ventricular function between the two infarct locations. Strauss et al. [12] suggest right ventricular involvement in inferior infarction after finding an increased ratio of right ventricular end-diastolic pressure to pulmonary artery occlusive pressure in patients with inferior infarction compared to those with anterior infarction of equivalent enzymatic size. They also noted a slightly (although not significantly) higher pulmonary occlusive pressure in those with anterior infarction, suggesting greater left ventricular dysfunction in this group. Our study utilizing QRS scoring and radionuclide imaging now confirms this greater involvement and reduced function of the left ventricle in patients with anterior infarction compared to those with inferior infarction of equivalent enzymatic size. In addition, our finding that perhaps the larger the myocardial infarction the relatively greater the left ventricular dysfunction in those with anterior infarctions compared to those with inferior infarctions suggests that the larger the myocardial infarction the proportionately greater the contribution of right ventricular necrosis to the enzyme release in inferior infarction. Alternatively, creatine kinase kinetics may differ according to the site and size of the infarction to account for these differences. The higher incidence of exercise-induced ST segment elevation in the anterior infarct group is further evidence of a discrepancy in left ventricular function between the two infarct locations, since this ST segment abnormality is thought to represent exercise-induced left ventricular regional wail abnormality independent of underlying coronary artery disease [31-331. Since we performed only resting nuclear studies we cannot confirm whether or not this exercise-induced ST segment elevation correlated with the development of left ventricular regional wall motion abnormality. However, De Feyter et al. [31] in a study involving 680 patients demonstrated a strong positive correlation between exercise-induced ST segment elevation and angiographically determined left ventricular dysfunction in those with previous myocardial infarction. The same study demonstrated a poor correlation between this electrocardiographic abnormality and the severity of coronary artery disease. They concluded that the development of ST segment elevation during exercise in patients with previous myocardial infarction was the result of mechanical left ventricular dysfunction. Similarly, Chahine et al. [32] in a trial involving 840
patients demonstrated that exercise-induced ST segment elevation reflects abnormal left ventricular wall motion rather than myocardial ischemia per se. The presence of ST segment elevation on exercise may be relevant to the poorer prognosis experienced by patients with anterior infarction. It was recently shown that ST segment elevation was the exercise-induced electrocardiographic abnormality which best predicted prognosis following infarction [34]. In that study, even when analysis was confined to transmural anterior myocardial infarction and account taken of left ventricular ejection fraction, exercise-induced ST segment elevation was found to be an independent predictor of subsequent cardiac events, including death. Therefore, it seems likely that this exercise electrocardiogram abnormality is more than merely a marker of transmural infarction. Both our observations of greater left ventricular regional wall motion abnormality and exercise-induced ST segment elevation in patients with anterior infarction are perhaps not surprising in view of previously published data suggesting that anterior infarction has a greater tendency for localized “infarct expansion” than inferior infarction. Eaton et al. [35] in a limited series of 28 patients showed that anterior infarcts are more at risk of “expanding” with thinning of the infarct zone combined with acute regional dilatation than inferior infarcts. It is anticipated that this process would lead to greater left ventricular regional wall abnormality both at rest and during exercise. Meizlish et al. [36] has confirmed that “infarct expansion” is a strong prognostic indicator, independent of left ventricular ejection fraction. The number of patients in our study is too small to assess prognosis. The latter has been well documented in other studies [ll-131. We were more concerned with examining differences in left ventricular function which may account for the difference in mortality between anterior and inferior infarcts of equivalent enzymatic size. Patients who had coronary angioplasty or coronary artery bypass surgery were excluded from the study to avoid having to account for any impact these interventions may have had on left ventricular function. The post-infarct prognostic parameters of ventricular ectopy (21 and coronary anatomy [7] were also not evaluated in this study. Arrhythmia analysis and comparison between groups would have necessitated extensive ambulant rhythm monitoring and a considerably larger series of patients than in our study to be valid. This would also be the case for comparison of coronary anatomy between the two groups and was outside the scope of this present study. In summary, we have demonstrated that anterior infarction compared with inferior infarction of equivalent enzymatic size has a lower global left ventricular ejection fraction in association with greater left ventricular regional wall abnormality. The latter probably relates to greater amount of necrosis of the left ventricle in the anterior infarct group as indicated by QRS scoring. Although not confirmed in this study, the differences in left ventricular function between the two infarct locations may relate to either right ventricular necrosis contributing to the cardiac enzyme release in some patients with inferior infarction, or possibly to varying creatine kinase kinetics according to the site of infarction. Given the powerful predictive role of left ventricular function on survival following myocardial infarction [l-7], our results provide a strong data basis for explaining the previously
166
established poorer prognosis of patients with anterior compared with those with inferior myocardial infarction size [ll-131.
myocardial infarction as of equivalent enzymatic
Acknowledgement The authors would like to thank the Department of Nuclear Medicine, Prince Alfred Hospital, Camperdown, N.S.W., Australia for development software for analysis of the gated heart studies.
Royal of the
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9 10 11 12 13
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Journal of Cardiology,
155
17 (1987) 155-168
Elsevier
IJC 00597
Differences in left ventricular function between anterior and inferior myocardial infarction of equivalent enzymatic size Mark E. Hands, Vince Antico, Peter L. Thompson, James S. Robinson, Brian L. Lloyd,
Joseph Hung,
Department of Cardiovascular Medicine, Sir Charles Gairdner Hospital, Queen Elizabeth II Medical Centre, Nedlands, Western Australia (Received
31 March
1987; accepted
18 May 1987)
Hands ME, Antic0 V, Thompson PL, Hung J, Robinson JS, Lloyd BL. Differences in left ventricular function between anterior and inferior myocardial infarction of equivalent
enzymatic
size. Int J Cardiol
1987;17:155-168.
The reasons for the poorer prognosis of anterior versus inferior myocardial infarction of equivalent enzymatic size remain uncertain. We investigated whether there are differences in left ventricuhu function between patients with anterior and inferior infarctions of equivalent enzymatic size to account for their differing outcomes. Clinical, serum enzyme, and electrocardiographic data were prospectively recorded in a consecutive series of patients less than 70 years of age with their first myocardial infarction. At 29 f 6 days following infarction, ejection fraction and left ventricular wall motion were assessed by gated heart scintigraphy and functional capacity by treadmill exercise testing in 19 patients with anterior and in 23 patients with inferior myocardial infarction. Peak creatine kiuase and QRS scores were used to estimate total infarct size and left ventricular infarct size respectively. The anterior infarcts were of similar size to the inferior infarcts as determined by peak creatine kinase (1444 [mean] f 1161 [SD] U/L versus 1484 [mean] f 1182 [SD] U/L, respectively, P = 0.91) and peak aspartate transaminases (174 f 112 U/L versus 164 f 102 U/L, P = 0.78). The anterior myocardial infarct group had a greater percentage of the left ventricle infarcted on QRS scoring tbau the inferior infarct group (25.9 f 14.4% versus 11.1 f 6.0% respectively, P = 0.0004), lower global left ventricular ejection fraction (45.8 f 16% versus 54.6 f 9.2%, P = 0.04)and greater left ventricular regional wall abnormality. A significant negative correlation
Correspondence to: Dr. Mark E. Hands. Francis Street, Boston, MA 02115, U.S.A.
0167-5273/87/$03.50
Cardiovascular
0 1987 Elsevier Science Publishers
Division,
Brigham
B.V. (Biomedical
and Women’s
Division)
Hospital,
75
156
existed between left ventricular ejection fraction and peak creatine kinase for both groups, but was more marked with anterior infarction (r = - 0.78, P < 0.01) compared with inferior infarction (r = -0.49, P -c0.05). Exercise-induced ST segment elevation was more frequent in the anterior than the inferior infarct group (59% versus 18%, P -K0.02). However, both infarct locations had similar exercise tolerance, exercise-induced angina and ST segment depression. Despite equivalence of infarct size of the two infarct locations on enzyme testing, anterior infarction was associated with greater abnormality of left ventricular function with lower resting global left ventricular ejection fraction; greater resting left ventricular regional wall abnormality and greater exercise-induced ST segment elevation. These differences probably contribute to the poorer prognosis of patients with anterior infarction compared to those with inferior infarction of equivalent enzymatic size, given the previously well-documented prognostic importance of left ventricular function. Key words:
Infarct
location;
Creatine
kinase;
Left ventricular
function;
QRS score
Introduction Factors influencing the prognosis of patients following myocardial infarction have been the subject of intensive investigation [l-14]. These studies have demonstrated that left ventricular function [l-7], infarct size [2,8-lo], history of previous infarction [4], coronary anatomy [7], and ventricular instability [2] are independent prognostic indicators following myocardial infarction. More recently, the location of myocardial infarction has been identified as an important factor influencing subsequent outcome, with patients with anterior myocardial infarction having a worse prognosis than those with inferior myocardial infarction of equivalent enzymatic size [ll-131. The reasons for this are not clear, given that cardiac enzyme levels reflect the extent of myocardial necrosis [9,10,14-171. However, right ventricle involvement in inferior infarctions has been documented [12,18-21]. Therefore, a possible explanation is that in a proportion of patients with inferior infarction, right ventricular necrosis contributes to the cardiac enzyme level, such that the latter may not accurately reflect the extent of left ventricular damage in this group of patients. Our study sought to evaluate the possibility that left ventricular function differs between anterior and inferior myocardial infarction of equivalent enzymatic size. We prospectively studied patients with anterior and inferior infarctions and the association between infarct site and the extent of left ventricular infarction based on QRS scoring; left ventricular function as assessed by radionuclide scanning; and functional capacity as determined by exercise treadmill testing. In addition, we sought to evaluate the extent of right ventricular involvement in inferior infarction which may account for any differences in left ventricular function between the two infarct locations.
157
Materials and Methods Patient Population Patients less than 70 years of age admitted to the Sir Charles Gairdner Hospital’s coronary care unit between January and September 1984, with definite acute myocardial infarction, were prospectively evaluated. Patients excluded from the study were: (1) those with previous myocardial infarction; (2) those in whom the site of infarction could not be located electrocardiographically, i.e., patients with left bundle branch block or no electrocardiographic changes; (3) those admitted to hospital after 24 hours from the onset of chest pain as their peak creatine kinase may have been missed; (4) those with factors other than myocardial necrosis known to influence peak creatine kinase levels, including thrombolytic therapy, intramuscular injections, direct current cardioversion, and underlying skeletal muscle disorder; (5) those who died or had coronary artery bypass surgery or coronary angioplasty during the first month following myocardial infarction; and (6) those who were considered unavailable for subsequent study because of distant domicile. Forty-two patients were entered into the study, 19 with anterior or anterolateral infarction and 23 with inferior or inferolateral infarction. Recruitment of patients ceased with the introduction of the routine use of intravenous streptokinase for patients with acute infarction in our unit. Clinical Data Clinical, serum enzyme, and electrocardiographic data were recorded during the patient’s hospital stay. Past history of myocardial infarction was documented if there was a history of typical pain supported by typical electrocardiographic or enzyme abnormalities. Clinical right ventricular infarction was diagnosed if the jugular venous pressure was elevated in the setting of myocardial infarction without clinical or radiological evidence of left ventricular failure. Left ventricular failure was defined as persistent basal lung crepitations associated with a third heart sound and/or radiological evidence of left heart failure during the patient’s hospital stay. Conduction disturbances were detected by computerized monitoring of the electrocardiogram and documented by analysis of 24 hours’ stored computer-generated electrocardiograms. During the initial 48 to 72 hours in hospital, the serum creatine kinase and aspartate transaminase were estimated at least twice daily. The peak level was the highest of these readings. The upper limit of normal creatine kinase in our laboratory is 180 international units per litre (U/L) and for aspartate transaminase is 40 U/L. The electrocardiographic site of infarction was assessed from the 12-lead electrocardiograms recorded at least daily for the first three days following admission. Anterior myocardial infarction was defined as the development of new Q waves and/or sequential ST segment elevations or T wave changes in leads Vl through V4.
158
Inferior myocardial infarction was defined as new Q waves and/or sequential ST segment elevations or T wave changes in leads II, III, and aVF. Anterolateral or inferolateral infarction was defined if, in addition, there were new Q waves or sequential ST segment elevations or T wave changes in leads V5, V6, and/or I and aVL. Repeat electrocardiogram for QRS scoring; gated heart scintigraphy for analysis of right and left ventricular function; and symptom-limited exercise treadmill test for assessment of functional capacity were performed at one month post myocardial infarction. These studies were performed within a 24 to 48 hour period of each other. QRS Scoring The electrocardiograms were all recorded on a three-channel Hewlett Packard recorder, with a frequency response of 0.5-110 Hz and speed of 25 mm/set. The 1Zlead electrocardiogram was used to derive a QRS score, based on the modified QRS scoring method by Wagner et al. [22], as an estimate of the size of left ventricular infarction. This 29-point scheme is based upon observed duration of Q and R waves and R/Q and R/S amplitude ratios in the standard 12-lead electrocardiogram (omitting leads III and aVR) in selected patients with initial anterior and inferior infarcts who succumbed as a result of the infarction. In that study, the amount of left ventricular myocardial necrosis was quantitatively assessed at autopsy. The higher the QRS score the greater the amount of left ventricular myocardial necrosis. Our 12-lead electrocardiographic tracings were read independently by two observers. The average of the two QRS scores was used. The percentage of the left ventricle infarcted was determined from previously published regression equations as follows: 96 in anterior
infarction
= 3.6
% in inferior
infarction
= 2.5
x x
QRS score + 3.2 [23] ; QRS score + 2.9 [24].
Radionuclide Studies Equilibrium gated heart scintigraphy was performed following in vitro labeling of autologous red blood cells [25]. Data were collected with a standard portable gamma camera (Technicare Sigma 420) onto a dedicated computer (DEC P.D.P. 11/34). Images were obtained in three views: (1) best septal left anterior oblique with caudal tilt obtained utilizing a 20 slant hole collimator, (2) 30 right anterior oblique, and (3) left lateral. Left and right ventricular ejection fractions were calculated from the left anterior oblique study, utilizing a semi-automatic program [26]. The left ventricular ejection fractions and the left ventricular time activity curve was calculated from multiple
159
regions of interest in the cardiac cycle. Bight ventricular ejection fraction is generated from diastolic and end-systolic regions of interest similar to the method of Maddahi et al. [27]. Data from 20 normal patients had previously documented the normal left ventricular ejection fraction to be 62.5 f 5.3% and the right ventricular ejection fraction 49.4 f 6.1%. Semi-quantitative assessment of regional wall motion was performed while viewing a cinematic display of all three views of the study. The method was adapted from that of Zaret et al. [28]. The left ventricle was divided into 11 equal segments. Anterior or inferior myocardial infarction could each potentially involve six of these segments, with involvement of the apical segment only being potentially common to both. Each segment was given a score according to its motion, i.e., 3 for normal, 2 for mildly hypokinetic, 1 for severely hypokinetic, 0 for akinetic, and -1 for clearly dyskinetic wall motion. Therefore, the lower the score the greater the left ventricular regional wall abnormality. If the left ventricle had entirely normal function, a score of 33 would be recorded. The right ventricle was considered separately as one segment with the same scoring system being applied. All studies were analyzed by the same blinded observer. Exercise Treadmill Testing
Symptom-limited exercise treadmill testing was performed at one month post myocardial infarction using the Naughton-Bake protocol [29]. Included in the recordings were the patient’s exercise tolerance, expressed in metabolic equivalents of oxygen consumptions (METS), presence or absence of chest pain typical of angina and the presence or absence of exercise-induced ST segment depression or elevation. ST segment depression was observed if, during exercise, the ST segment fell 2 1 mm from the resting baseline 80 msec after the J point. ST segment elevation was recorded if the ST segment rose > 1 mm from the resting J point. Analysis of Data
Differences between patient characteristics for the two infarct locations were examined. Discrete variables were tested against the &i-square distributions, with the use of the Yates correction where appropriate. For continuous variables the Student t-test was applied. The non-parametric Spearman rank correlation was utilized to compare the distribution of patients in each subgroup of peak creatine kinase for both infarct locations. A P value of less than 0.05 was considered significant. Results
Both the anterior and inferior infarct groups had similar peak creatine kinase (1444 [mean] + 1161 [SD] U/L versus 1484 [mean] rt 1182 [SD] U/L, respectively, P = 0.91) and similar peak aspartate transaminase (174 + 112 U/L versus 164 k 102 U/L, respectively, P = 0.78) (Table 1). In addition, non-parametric Spearman rank
160 TABLE
1
Characteristics
of patient
population
studied.
Anterior Age (years) Male : female ratio Peak CK (U/L) Peak AST (U/L) Q wave MI (W) RV infarction (%) LV failure (W) 2/3 AV block (W) Beta-blocker (W) Calcium antagonists Nitrates (W) Diuretics (%) Digoxin (W)
(W)
MI n = 19
59.2 + I 3.6 : 1 1444* 1161 174+ 112 13 0 33 5 42 21 36 21
Inferior
MI n = 23
Significance
4.3 35 5 39 21 36 27 9
5
P value
NS NS NS NS NS NS NS NS NS NS NS NS NS
53.4k11.7 4.75 : 1 1484* 1182 164 f 102 65
MI = myocardial infarction; n = number of patients; NS = not significant (P creatine kinase; AST = aspartate transaminase; RV = right ventricular (clinical): AV = atrioventricular; 2 = second degree; 3 = third degree; % percentage.
value > 0.05); CK = LV = left ventricular;
correlation testing indicated that there were no significant differences in the number of patients in the different subgroups of peak creatine kinase (Fig. 1). Patients in the two infarct locations were similar for age, sex, Q-wave infarction, clinical and
cl
o-a
a -
16
16
CAEATINE
Fig. 1. Distribution
of infarct
-
24
24 KINASE
-
32
32 (U/L
INFERIOR
MI
n
= 23
ANTERIOR
MI
n
=
-
40
x
102)
40
-
48
size based on peak creatine kinase (CK) level. MI = myocardial n = number of patients; U/L = units per liter.
48
19
-
56
infarction;
161 TABLE
2
Electrocardiographic
and gated heart scintigraphy Anterior
QRS score (from ECG)
6.3k
LV infarcted (W) (from QRS score) LVEF (%)
MI = myocardial electrocardiograph;
4.0
25.9* 14.4 45.8 f 16
LV segments (with abnormal motion) LV regional wall abnormality score RVEF (S) RV wall motion abnormality (%)
MI n = 19
5.4*
3.4
25.5k 52.5k
7.8 9.3
26
results Inferior
3.3+
MI n = 23
2.4
11.1 & 6.0 54.6 k 9.2 3.8*
Significance
P value
0.008 0.0004 0.04
3.0
0.14
29.3+ 5.9 54.4*11.2
0.09 NS
39
NS
infarction; n = number of patients; NS = not significant (P > 0.05); ECG = LV = left ventricular; RV = right ventricular; EF = ejection fraction; % = percentage.
radiological evidence of left ventricular failure, clinical evidence of right ventricular infarction, conduction disturbances, and prescription of medications that could potentially influence left ventricular function (Table 1). In Table 2 are shown estimates of the left ventricular infarct size based on the 12-lead electrocardiogram at one month post infarction. The anterior infarct group had a significantly greater QRS score than the inferior infarct group (6.3 + 4.0 versus 3.3 k 2.4, P = 0.008). Accordingly, the derived percentage of left ventricle infarcted was significantly greater in the anterior infarct group than the inferior infarct group (25.9 + 14.4% versus 11.1 + 6.0%, P = 0.0004). The results of the gated heart scintigraphy are also displayed in Table 2. The anterior infarct group had significantly lower mean global left ventricular ejection fraction than the inferior group (45.8 k 16% versus 54.6 + 9.4%, P = 0.04). The number of left ventricular segments with abnormal motion in the anterior infarct group tended to be greater than the inferior infarct group, although this did not achieve statistical significance (5.4 + 3.4 versus 3.8 f 3.0, P = 0.14). Estimation of left ventricular regional wall abnormality as described in the methods showed a similar but not significant trend with the anterior infarct group having a lower LV regional wall score of 25.5 &-7.8 as compared with the inferior infarct group score of 29.3 + 5.9 (P = 0.09). Figs. 2 and 3 demonstrate the correlations between left ventricular ejection fraction and peak creatine kinase for the anterior and inferior infarct groups respectively. Inverse correlations are evident for both anterior (r = -0.78) and inferior (r = -0.49) infarction, the correlation being more significant for the anterior than inferior infarct group (P < 0.01 versus P < 0.05, respectively). The graphs illustrate that the larger the infarct the greater the impairment of left ventricular function for anterior infarction compared with inferior infarction of equivalent enzymatic size.
162 ANTERIOR
M
I
loo-
800 60-
=
19
=
-0.78
*
P
<
0.01
0
0 u.
n r
’
w > -1
40-
20-
O-0
8
16
24
CREATINE
Fig. 2. Correlation between left ventricular in anterior myocardial infarction
32
KINASE
40
[ U/L
LA.
66
x 102 I
ejection fraction (LVEF) and peak creatine kinase (CK) levels (MI). n = number of patients; U/L = units per liter. M
INFERIOR
80
48
I
”
=
r
=
x
p
23 -0.49
<
0.05
l
60
w > 40
20
0
I
I
I
8
16 CREATINE
Fig. 3. Correlation between left ventricular in inferior myocardial infarction
I
24
1
32 KINASE
40 [ut
1
48
1
66
x102]
ejection fraction (LVEF) and peak creatine kinase (CK) levels (MI). n = number of patients: U/L = units per liter.
163 TABLE
3
Symptom-limited
exercise treadmill
test (Naughton-Balke
Anterior Exercise workload (METS) Angina ST segment depression ST segment elevation
II = 17
6.5+1.7 29% 41% 59%
MI = myocardial infarction; n = number equivalents of oxygen consumption.
protocol). Inferior
n = 22
7.2+1.8 23% 52% 18% of patients;
NS = not significant
Significance
P value
NS NS NS 0.02
(P > 0.05); METS = metabolic
Right ventricular ejection fraction was similar for both anterior and inferior infarct groups (52.9 + 9.3% versus 54.4 k 11.2%. respectively). However, a greater percentage of patients with inferior infarction had visually observed right ventricular wall motion abnormality than those with anterior infarction (39% versus 26%, respectively), although this difference did not achieve statistical significance (Table 2). Twenty-two of the 23 patients with inferior infarction underwent exercise testing. The remaining patient in this group was excluded due to unstable angina. Two patients in the anterior infarct group were not tested. One of these had unstable angina and the other had a large left ventricular thrombus demonstrated on cross-sectional echocardiography. Both anterior and inferior infarct groups had similar exercise capacities (6.3 k 1.7 METS versus 7.2 f 1.8 METS, respectively, NS) (Table 3). They also had similar frequencies of exercise-induced angina and exercise-induced ST segment depression. Notably, patients with anterior infarction had a significantly greater incidence of exercise-induced ST segment elevation than those with inferior infarction (59% versus 18% respectively, P = 0.02).
Discussion Our results show that there is greater left ventricular involvement and dysfunction in patients with anterior myocardial infarction than in those with inferior myocardial infarction of equivalent enzymatic size. This conclusion is drawn from the results obtained from assessment of (1) left ventricular infarct size by QRS scoring, and (2) left ventricular function by gated heart scintigraphy, utilizing the parameters of global left ventricular ejection fraction and regional wall motion. Given that less left ventricular impairment occurred in patients with inferior infarction than those with anterior infarction of equivalent enzymatic size, we conclude that the enzyme release in the former is not all secondary to left ventricular damage. Previous studies with hemodynamic monitoring [12], thallium201 scintigraphy [18], blood pool imaging [19], and necropsy (201 have suggested the involvement of the right ventricle in inferior myocardial infarction. Therefore, right ventricular necrosis may contribute to enzyme release in some patients with inferior infarction which may explain the differences in left ventricular function between the
164
two infarct locations. Our results are in keeping with this explanation with greater radionuclide right ventricular wall motion abnormality being detected in the inferior infarct group, but are not conclusive. The lack of significant difference in right ventricular function found between our two infarct groups may relate to the lack of specificity of the radionuclide technique used to evaluate right ventricular function. It is well documented that spontaneous early reperfusion in myocardial infarction may significantly contribute to the magnitude of the peak creatine kinase level independent of myocardial necrosis [30]. Therefore, an alternative explanation for our results may be that early spontaneous reperfusion occurs more often in patients with inferior myocardial infarction than those with anterior myocardial infarction. The latter has yet to be established. However, if this postulate were true then indeed greater left ventricular impairment would be expected in anterior infarction compared with inferior infarction of equivalent enzymatic size. In this case, there need not be any difference in right ventricular function to explain the differences in left ventricular function between the two infarct locations. Strauss et al. [12] suggest right ventricular involvement in inferior infarction after finding an increased ratio of right ventricular end-diastolic pressure to pulmonary artery occlusive pressure in patients with inferior infarction compared to those with anterior infarction of equivalent enzymatic size. They also noted a slightly (although not significantly) higher pulmonary occlusive pressure in those with anterior infarction, suggesting greater left ventricular dysfunction in this group. Our study utilizing QRS scoring and radionuclide imaging now confirms this greater involvement and reduced function of the left ventricle in patients with anterior infarction compared to those with inferior infarction of equivalent enzymatic size. In addition, our finding that perhaps the larger the myocardial infarction the relatively greater the left ventricular dysfunction in those with anterior infarctions compared to those with inferior infarctions suggests that the larger the myocardial infarction the proportionately greater the contribution of right ventricular necrosis to the enzyme release in inferior infarction. Alternatively, creatine kinase kinetics may differ according to the site and size of the infarction to account for these differences. The higher incidence of exercise-induced ST segment elevation in the anterior infarct group is further evidence of a discrepancy in left ventricular function between the two infarct locations, since this ST segment abnormality is thought to represent exercise-induced left ventricular regional wail abnormality independent of underlying coronary artery disease [31-331. Since we performed only resting nuclear studies we cannot confirm whether or not this exercise-induced ST segment elevation correlated with the development of left ventricular regional wall motion abnormality. However, De Feyter et al. [31] in a study involving 680 patients demonstrated a strong positive correlation between exercise-induced ST segment elevation and angiographically determined left ventricular dysfunction in those with previous myocardial infarction. The same study demonstrated a poor correlation between this electrocardiographic abnormality and the severity of coronary artery disease. They concluded that the development of ST segment elevation during exercise in patients with previous myocardial infarction was the result of mechanical left ventricular dysfunction. Similarly, Chahine et al. [32] in a trial involving 840
patients demonstrated that exercise-induced ST segment elevation reflects abnormal left ventricular wall motion rather than myocardial ischemia per se. The presence of ST segment elevation on exercise may be relevant to the poorer prognosis experienced by patients with anterior infarction. It was recently shown that ST segment elevation was the exercise-induced electrocardiographic abnormality which best predicted prognosis following infarction [34]. In that study, even when analysis was confined to transmural anterior myocardial infarction and account taken of left ventricular ejection fraction, exercise-induced ST segment elevation was found to be an independent predictor of subsequent cardiac events, including death. Therefore, it seems likely that this exercise electrocardiogram abnormality is more than merely a marker of transmural infarction. Both our observations of greater left ventricular regional wall motion abnormality and exercise-induced ST segment elevation in patients with anterior infarction are perhaps not surprising in view of previously published data suggesting that anterior infarction has a greater tendency for localized “infarct expansion” than inferior infarction. Eaton et al. [35] in a limited series of 28 patients showed that anterior infarcts are more at risk of “expanding” with thinning of the infarct zone combined with acute regional dilatation than inferior infarcts. It is anticipated that this process would lead to greater left ventricular regional wall abnormality both at rest and during exercise. Meizlish et al. [36] has confirmed that “infarct expansion” is a strong prognostic indicator, independent of left ventricular ejection fraction. The number of patients in our study is too small to assess prognosis. The latter has been well documented in other studies [ll-131. We were more concerned with examining differences in left ventricular function which may account for the difference in mortality between anterior and inferior infarcts of equivalent enzymatic size. Patients who had coronary angioplasty or coronary artery bypass surgery were excluded from the study to avoid having to account for any impact these interventions may have had on left ventricular function. The post-infarct prognostic parameters of ventricular ectopy (21 and coronary anatomy [7] were also not evaluated in this study. Arrhythmia analysis and comparison between groups would have necessitated extensive ambulant rhythm monitoring and a considerably larger series of patients than in our study to be valid. This would also be the case for comparison of coronary anatomy between the two groups and was outside the scope of this present study. In summary, we have demonstrated that anterior infarction compared with inferior infarction of equivalent enzymatic size has a lower global left ventricular ejection fraction in association with greater left ventricular regional wall abnormality. The latter probably relates to greater amount of necrosis of the left ventricle in the anterior infarct group as indicated by QRS scoring. Although not confirmed in this study, the differences in left ventricular function between the two infarct locations may relate to either right ventricular necrosis contributing to the cardiac enzyme release in some patients with inferior infarction, or possibly to varying creatine kinase kinetics according to the site of infarction. Given the powerful predictive role of left ventricular function on survival following myocardial infarction [l-7], our results provide a strong data basis for explaining the previously
166
established poorer prognosis of patients with anterior compared with those with inferior myocardial infarction size [ll-131.
myocardial infarction as of equivalent enzymatic
Acknowledgement The authors would like to thank the Department of Nuclear Medicine, Prince Alfred Hospital, Camperdown, N.S.W., Australia for development software for analysis of the gated heart studies.
Royal of the
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