(Circulation. 1995;92:710-719.)
© 1995 American Heart Association, Inc.
Articles |
Relation Between Ischemia Time, Infarct Size, and Left Ventricular Function in Humans
From the Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.
Correspondence to Dr Richmond W. Jeremy, Department of Cardiology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, 2050, New South Wales, Australia.
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Abstract |
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Background Experimental studies indicate that duration of ischemia is a major determinant of myocardial infarct size, but only limited information is available about the relation between ischemia time and infarct size in individual patients. This prospective study sought to document the role of ischemia time as a determinant of infarct size in humans.
Methods and Results We studied 61 patients (50 men, 11 women) 57±11 years old admitted with a first infarct (31 anterior, 30 inferior) who underwent continuous 12-lead ECG monitoring to document ischemia time. Infarct size (32-point QRS score on day 7) and changes in regional myocardial wall motion (echocardiography) during the following month were related to ischemia time. Among patients with <3 hours of ischemia (n=16), mean infarct size on day 7 was 21±13% of potential infarct size; in patients with 3 to 6 hours of ischemia (n=23), infarct size was 38±18% of potential (P<.05 versus 0 to 3 hours of ischemia); and in patients with 6 to 9 hours of ischemia (n=10), infarct size was 66±14% of potential (P<.05 versus 3 to 6 hours). In contrast, the 12 patients with an ischemia time >9 hours had a final infarct size of 77±10% of potential (P<.01 versus 3 to 6 hours). Multivariate regression identified size of risk region, duration of ischemia, and degree of initial ST-segment elevation as independent predictors of infarct size, of which the most important variable was ischemia time. The regression models accurately predicted both individual absolute infarct size (R2=.83) and individual infarct/risk ratio (R2=.74). Patients with <6 hours of ischemia exhibited significant recovery of myocardial wall motion by day 7 (wall motion score, 2.1±1.4 versus 5.7±3.2 on day 1, P<.01). Patients with 6 to 9 hours of ischemia had some recovery by 1 month (score, 6.3±4.4 versus 10.9±3.8 on day 1, P<.01), but patients with >9 hours of ischemia had little recovery of wall motion by 1 month (score, 10.3±4.5 versus 12.8±3.1 on day 1, P<.05).
Conclusions Measurement of ischemia time allows improved prediction of infarct size in humans. Significant myocardial salvage and functional recovery may be achieved by reperfusion up to 9 hours after coronary occlusion. Continuous ST-segment monitoring should be used to measure ischemia time and guide interventions to reperfuse the infarct artery.
Key Words: myocardial infarction • reperfusion • ischemia • electrocardiography
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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The benefits of thrombolytic therapy in acute myocardial infarction are well established.1 2 3 Large-scale clinical trials have shown that early thrombolytic therapy is associated with better ventricular function4 5 and improved survival after infarction.1 2 3 6 The benefits of thrombolysis in individual patients have been more difficult to ascertain.7 One important question relates to the time window in which thrombolysis may salvage myocardium in the individual patient. The answer to this question requires definition of the relation between ischemia time and infarct size in the individual.8 9 A second question concerns the recovery of regional myocardial function after ischemia. There is evidence to support the hypothesis that postischemic contractile dysfunction (stunning) is a significant entity in humans,10 but the time course of recovery of stunning and its determinants remain uncertain.
Experimental studies have shown that the major determinants of infarct size are the extent of the ischemic risk region, the duration of ischemia, and collateral blood flow to the ischemic region.11 12 13 14 15 Myocardial necrosis is a time-dependent phenomenon following coronary occlusion, and in the canine model, necrosis is largely complete after 6 hours.14 15 Similarly, the severity and duration of ischemia have also been shown to be determinants of the severity of postischemic stunning.16 Although these findings form an important basis for the clinical application of thrombolytic therapy, the role of ischemia time as a determinant of infarct size and subsequent regional contractile function in individual patients has not been documented. Previously, estimates of ischemia time have been based on the time from onset of symptoms to initiation of thrombolytic therapy,8 17 but the variable response of individual patients to thrombolytic therapy confounds this approach. The findings of a recent angioplasty study do, however, support a relation between ischemia time and recovery of regional myocardial function after anterior infarction.18
The application of ECG ST-segment monitoring offers a means for measuring ischemia time during myocardial infarction in humans. Reperfusion of the infarct artery is associated with a rapid decrease in ST-segment elevation, while persistent occlusion of the infarct artery is associated with prolonged ST elevation.19 20 21 Angiographic studies have confirmed the utility of ST-segment monitoring as a marker of myocardial ischemia.22 23 This study therefore used continuous 12-lead ST-segment monitoring to measure ischemia time in patients presenting with acute infarction and to determine the relations between ischemia time, infarct size, and subsequent recovery of myocardial contractile function. It was hypothesized that measurement of ischemia time would improve prediction of infarct size in individual patients and that shorter ischemia times would correlate with smaller infarct sizes and better left ventricular function in the convalescent period.
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Methods |
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Patient Group
Patients presenting with a first myocardial infarction were eligible for entry into the study. Transmural myocardial ischemia was diagnosed in the presence of typical central chest pain of >30 minutes' duration and ST-segment elevation of at least 100 µV in two or more contiguous leads on the 12-lead ECG. Exclusion criteria were age >75 years, valvular or myopathic heart disease, previous coronary artery bypass surgery, right or left bundle branch block, and presentation >12 hours after the onset of chest pain. All patients gave their written, informed consent to participate in the study, which was approved by the hospital ethics committee. Patients were treated with aspirin, oral or cutaneous nitrates, and thrombolytic therapy (streptokinase 1.5 million units IV over 60 minutes or tissue-type plasminogen activator 100 mg IV over 3 hours) unless contraindicated. Subsequently, patients received a continuous intravenous infusion of heparin to maintain the partial thromboplastin time at 80 to 100 seconds. Other treatment, including ß-adrenergic blockers and calcium antagonists, was at the discretion of the attending physician.
Measurement of Ischemia Time
A 12-lead ECG was acquired at
the time of presentation, and
subsequent ECGs at 4, 8, 12, and 24 hours after admission and daily
thereafter. The lead positions were marked on the anterior chest wall
for these serial recordings. Continuous 12-lead ST-segment monitoring
was done with a portable, microprocessor-based unit (ID-12
electrocardiograph, Mortara Instrument Co), which was applied after the
first 12-lead ECG. This monitor scanned the 12-lead ECG at 20-second
intervals, storing the 12-lead recording every 15 minutes or if any
ST-segment shift (>100 µV in two leads or >200 µV in one lead)
was detected.19 The mean duration of ST-segment monitoring
in this patient group was 926±584 minutes after presentation, and
the data from the ST-segment monitor were then transferred to a
personal computer for analysis.
The magnitude of ST-segment elevation
was measured at 60 ms after the
J-point in all leads with >100-µV ST
elevation.20 The ST-segment elevation in excess of 100
µV in each of these leads was summed to calculate total ST elevation
(STsum, µV). The admission ECG with maximal ST
elevation (STmax) was identified as a measure of the
severity of ischemia.24 Reperfusion of the infarct
artery was defined as the time when STsum decreased to
25% of STmax. If STsum had not decreased to
25% of STmax within 12 hours of the onset of chest pain,
the infarct artery was considered to have remained occluded. Ischemia
time (Tisc) was calculated as the time from onset of
persistent chest pain to the time of reperfusion, to a maximum of 12
hours. The total ischemic burden was indexed as the product of
ischemia time and maximal ST elevation: ischemia
index=STmaxxTisc.
ECG QRS Scores
Infarct size was estimated from the 12-lead
ECG according to a
32-point QRS
score,25 26 27 28 in which
each point
represents approximately 3% of the left ventricular mass. This
scoring system, originally developed from anatomic studies of anterior
and inferior infarcts,29 30 has since been used in
clinical studies of infarct size limitation.31 32 The
ECG
showing maximum ST elevation at the time of admission and the ECG on
day 7 were each scored by two independent observers who were unaware of
the data on ischemia times. Differences between observers were
resolved by consensus with a third observer. On the admission ECG, all
leads exhibiting 
100-µV ST segment elevation were assigned the
maximum potential QRS score for that lead. For patients with inferior
infarcts, leads V1 and V2 were included as a
posterior extension of the risk region if there was 100-µV ST
depression in these leads on the admission ECG. Previous studies in our
department have shown that such ST depression in leads V1
and V2 is associated with posterior extension of
201Tl perfusion defects in patients with inferior
infarcts.33 34 The sum of these initial scores
(QRS0) was considered to represent potential
maximum infarct size for that patient (analogous to extent of the
ischemic risk region). The QRS score at 7 days
(QRS7) was considered to represent the actual size
of the infarct in each patient. The ratio
(QRS7/QRS0) was a measure of actual
infarct size relative to potential infarct size. Validation studies in
our laboratory have shown that QRS0 is correlated with the
extent of the perfusion defect on 201Tl single photon
emission computed tomography (SPECT) scan (r=.79). The QRS
score on day 7 is also correlated with the extent of infarction on
predischarge 99mTc-pyrophosphate SPECT (r=.78)
and is inversely correlated with left ventricular ejection fraction at
1 month after infarction (r=-.74).
Coronary Angiography
Coronary angiography was performed in 40
patients (65%) at a
mean of 6±3 days after infarction. Angiography was performed via the
right femoral artery by standard percutaneous techniques, and multiple
views were obtained of each coronary artery. Perfusion of the infarct
artery was graded according to the criteria of the TIMI study
group35 by an independent observer. A TIMI score of 0 or 1
indicated an occluded infarct artery and a score of 2 or 3, a patent
infarct artery. The angiographic findings were compared with the
ST-segment data to correlate changes in ST-segment elevation with
subsequent perfusion status of the infarct artery.
Echocardiography
Serial measurements of regional myocardial
wall motion were made
in each patient by echocardiography (Hewlett Packard Sonos 1000). The
first echocardiogram was obtained within 24 hours of the onset of chest
pain, and subsequent echocardiograms were obtained on days 3 and 7 and
at 1 month after infarction. Cross-sectional views of the left
ventricle were obtained from left parasternal and apical windows and
recorded on videotape. Only patients in whom the entire left ventricle
could be clearly visualized on each occasion were analyzed. Those
patients who underwent coronary artery bypass surgery or angioplasty
during the month after infarction were excluded. Regional myocardial
wall motion was scored by an observer blinded to the
electrocardiographic and angiographic data. The left ventricle was
divided into 14 regions, and wall motion in each region was graded as
normal (score of 0), hypokinetic (1), akinetic (2), or dyskinetic (3).
The sum of the scores for the individual regions yielded a total left
ventricular wall motion score, with higher scores being associated with
more severe contractile impairment.
Data Analysis
Demographic variables were compared between
patient groups by
Student's t test or 
2 testing as
appropriate.36 Differences in infarct size and left
ventricular wall motion scores were compared between groups by ANOVA,
with comparison of group means by Newman-Keuls test. Results are
reported as mean±SD, and a value of P<.05 is reported as
significant. The relations between the independent variables of risk
region size, severity of ischemia (indexed by
STmax), and duration of ischemia and the
dependent variable of infarct size were determined by both univariate
and multivariate regression.37 The
accuracy of the regression model was then tested by comparing the
predicted and observed infarct sizes and infarct/risk ratios for each
patient.
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Results |
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Sixty-one patients (50 men, 11 women) with a mean age of 57±11 years were enrolled. There were 31 patients with anterior infarcts and 30 with inferior infarcts. Forty-four patients (72%) had a history of smoking, 19 (31%) had hypercholesterolemia, 27 (43%) were hypertensive, and 12 (20%) were diabetic. The mean time from onset of chest pain to hospital admission was 148±104 minutes in patients with anterior infarcts and 118±91 minutes in patients with inferior infarcts (P=NS). Fifty-one patients (23 with anterior, 28 with inferior infarcts) received thrombolytic therapy. The time from chest pain to initiation of thrombolytic therapy was similar in patients with anterior (199±119 minutes) and inferior (157±97 minutes) infarcts. One patient died on day 4, and his day 4 QRS score was included as final infarct size. No other patients died before hospital discharge.
ST-Segment Monitoring
The mean duration of ST-segment
monitoring was 926±584 minutes.
There were 50 patients (23 with anterior, 27 with inferior infarcts)
who exhibited resolution of ST-segment elevation, consistent with
reperfusion of the infarct artery, within 12 hours of the onset of
chest pain. Sixteen patients exhibited a decrease in ST-segment
elevation within 3 hours of the onset of chest pain, 23 between 3 and 6
hours, and 10 between 6 and 9 hours. Twelve patients had prolonged
ischemia, of whom 1 had resolution of ST elevation between 9
and 12 hours, and the remaining 11 (8 with anterior, 3 with inferior
infarcts) had persistent ST-segment elevation for at least 12 hours
after the onset of chest pain. The clinical features of these patients
are compared in Table 1
. Among the 40 patients who
underwent coronary angiography, 33 had a patent infarct artery, of whom
31 had exhibited resolution of ST elevation within 12 hours of chest
pain, consistent with reperfusion of the infarct artery. The remaining
2 patients did not have early resolution of ST elevation, suggesting
late recanalization of the infarct artery. There
were 7 patients with an occluded infarct artery, of whom 6 had no
resolution of ST elevation during monitoring. The seventh patient
showed initial resolution of ST elevation but developed further chest
pain and ST elevation of >12 hours' duration on day 2, consistent
with late reocclusion of the infarct artery.
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The ST-segment changes
that occurred during the ischemic period
are compared for 2 patients with anterior infarcts in Fig 1.
The top panel shows the pattern of early resolution
of ST elevation, which was associated with a subsequent small infarct
(day 7 QRS score of 2). In contrast, the pattern of persistent ST
elevation (bottom panel) was associated with a large infarct (day 7 QRS
score of 8). The principal difference between these patients in the
acute phase was the duration of ischemia, since infarct site
and extent and degree of early ST elevation were similar.
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Univariate Predictors of Infarct Size
Infarct size, measured
by the QRS score at 7 days, is compared
with the potential maximum QRS score for each patient in Fig 2.
There is considerable variation in the observed
infarct sizes, but nearly all patients exhibited a lower QRS score at
day 7 than was predicted from the initial ECG, consistent with the
hypothesis that infarct size is dependent on several factors in
addition to extent of the risk region. The relation between maximum ST
sum (STmax) at the time of presentation and
subsequent infarct size (QRS7) is shown in Fig 3.
There is a moderate correlation between
STmax and subsequent absolute infarct size (top panel,
r=.54), but STmax alone is a poor predictor of
the individual infarct/risk ratio (bottom panel,
r=.37).
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The relation between ischemia time and infarct
size is shown in
Fig 4. The absolute infarct size was related to the
duration of ischemia (top panel, r=.69), and the
infarct/risk ratio was closely related to the ischemia time
(bottom panel, r=.83). This nonlinear relation shows that
the infarct/risk ratio increases most rapidly during the first few
hours after coronary occlusion, with a slower rate of increase beyond 6
hours of ischemia.
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There were no significant differences in age or
hemodynamics between
patients with short ischemia times and those with prolonged
ischemia (Table 1
). The extent of the ischemic risk
region (potential QRS score) was independent of ischemia time.
There were, however, major differences in the QRS score at day 7
between patients with short ischemia times and those with
prolonged ischemia. In both the anterior and inferior infarct
groups, the QRS score at day 7 increased as ischemia time
increased. Among the 16 patients with an ischemia time <3
hours, the mean infarct/risk ratio was 21±13%. In contrast, among
patients with an ischemia time of 6 to 9 hours, the mean
infarct/risk ratio was 66±14% (P<.01 versus 0 to 3
hours), and among the 12 patients with an ischemia time >9
hours, the mean infarct/risk ratio was 77±10% (P<.01
versus 3 to 6 hours).
The relation between the ischemia (ST) index
(product of
ischemia time and maximum sum of ST elevation) and the QRS
score at 7 days is illustrated in Fig 5 (top panel).
Similarly, the proportion of the ischemic risk region
undergoing infarction (ratio of observed to potential QRS score, bottom
panel) was related to the ischemia index. This curvilinear
relation illustrates the role of the ischemia burden as a
determinant of infarct size. Those patients with a low ischemia
index, reflecting a short ischemia time, less severe
ischemia, or both, have a low infarct/risk ratio. In contrast,
patients with a high ischemia index, due to either more severe
ischemia or a prolonged ischemia time, have a larger
infarct/risk ratio. The patients at greatest risk are those who have
both severe ischemia and a prolonged ischemia time, in
whom the infarct/risk ratio approaches 100%.
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Multivariate Predictors of Infarct Size
The univariate
regression relations between individual independent
variables and the dependent variable of infarct size at 7 days are
summarized in Table 2. Univariate analysis
identified heart rate, potential QRS score, STmax,
and ischemia time as significant predictors of final infarct
size. The most significant univariate predictor was the
ischemia (ST) index (r=.86), reflecting the combined
contributions of ischemia time and severity of
ischemia. The relative contributions of heart rate,
rate-pressure product, potential infarct size, and severity and
duration of ischemia to prediction of final infarct size were
determined by multiple linear regression (Table 3). In
the first model, the dependent variable was infarct size as a
percentage of the total left ventricle. This model accounted for 83%
of the variation in final infarct size and identified rate-pressure
product, potential maximum QRS score, STmax, and
ischemia time as significant independent predictors of infarct
size. In this model, duration of ischemia was the most
significant predictor identified. In the second model, the dependent
variable was infarct size as a percentage of the ischemic risk
region. This model accounted for 74% of the observed variation in
infarct size, identifying ischemia time and STmax
as independent predictors of the proportion of the risk region
undergoing infarction. The absolute infarct size and the infarct/risk
ratio for each patient, predicted by these multivariate
regression models, are compared with observed infarct size in Fig
6. The model accurately predicted absolute infarct size
(top panel). The correlation between predicted and observed infarct
size was .92, and the regression relation did not differ from the line
of identity. Overall, the predicted and observed infarct sizes differed
by <5% of left ventricular mass in 50 of 61 patients (82%) and by
<7% in 58 of 61 patients (95%). Similarly, the
multivariate model accurately predicted the individual
infarct/risk ratio (bottom panel), and the relation between predicted
and observed ratios (r=.87) did not differ from the line of
identity. With application of this model, predicted and observed
infarct sizes differed by <10% of the risk region in 37 of 61
patients (61%) and by <15% in 45 of 61 patients (74%). This model,
however, tended to overestimate infarct size in patients with small
infarcts.
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Regional Myocardial Wall Motion
Changes in regional
myocardial wall motion that occurred during
the month after infarction are compared in Table 4 for
patients with different ischemia times. There were 34 patients
(30 male) who did not undergo surgical revascularization during this
period and who had serial echocardiograms of sufficient quality to
permit serial characterization of wall motion in each of the 14 left
ventricular regions. All patients exhibited regional wall motion
abnormalities on day 1, and more severe contractile impairment was
observed in patients with ischemia times >6 hours. In patients
with <6 hours of ischemia, some improvement in regional wall
motion was evident by day 3, and further improvement was observed by
day 7. Among patients with ischemia times between 6 and 9
hours, no improvement in regional wall motion was documented by day 7,
but during the subsequent month, these patients did exhibit significant
recovery of regional wall motion. The patients with ischemia
times >9 hours exhibited the most severe wall motion abnormalities and
had only limited functional recovery by 1 month.
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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This study describes the role of ischemia time as a determinant of infarct size and subsequent left ventricular function in individual patients with myocardial infarction. In experimental studies, the principal determinants of infarct size are extent of the ischemic risk region, duration of ischemia, collateral blood flow, and myocardial oxygen demand during ischemia.11 12 13 14 15 38 Quantification of the contribution of these factors in humans has been difficult, and previous clinical studies have been able to account for only
50% of
the variation in infarct size between
patients.32 39 40 41
The recent radionuclide studies by Christian and
coworkers8 demonstrated the relation between extent of the
ischemic risk region and subsequent infarct size in humans, but
the role of ischemia time in individuals has not been clearly
defined to date. The present study, using continuous ST-segment
monitoring, has shown that ischemia time is a major determinant
of both infarct size and subsequent recovery of myocardial function in
the individual patient. As with the experimental data, the severity and
duration of ischemia are synergistic in determining infarct
size. The present multivariate model accounted for
80% of the individual variation in infarct size, and the factors
identified as independent predictors of infarct size are analogous to
those previously documented in the experimental setting. The rate of
recovery of contractile function in the convalescent phase is inversely
related to the duration of ischemia. Those patients with <6
hours of ischemia exhibited significant functional recovery
within 7 days, in contrast to those with more prolonged
ischemia.
Ischemia Time and Infarct Size
Myocardial necrosis in
anesthetized dogs is time
dependent,15 16 progressing as a wave front from
subendocardium to subepicardium, with complete necrosis after 6 hours.
Experimental thrombolytic studies also suggest that little myocardial
salvage is achieved after more than 6 hours after coronary
occlusion.42 These findings underlie the present
clinical use of thrombolytic
therapy.6 17 43
Measurement of ischemia time is critical. The gold standard would be continuous angiographic monitoring of the infarct artery, but this is not feasible in a large number of patients. The use of continuous ST-segment monitoring was first described by Krucoff et al,19 20 who showed that a rapid decrease in the extent and severity of ST-segment elevation was an indicator of reperfusion of the infarct artery. In contrast, prolonged ST elevation indicates persistent occlusion or very late reperfusion of the infarct artery.19 20 44 Subsequently, the use of changes in ST segment elevation as an indicator of reperfusion has become widespread.44 45 46 Our own group previously examined the utility of ST segment monitoring in predicting patency of the infarct artery and further extended the application of ST monitoring to include detection of reocclusion of the infarct artery after thrombolysis.21 22 The validity of rapid resolution of ST elevation as a marker of reperfusion has been confirmed by the angiographic studies of Shah and coworkers.23
One
consideration in determining the time of reperfusion of the infarct
artery is the threshold applied to the ST-segment measurements. It has
been shown that each patient should serve as his or her own control and
that the relative decrease in total ST elevation is a more accurate
marker of reperfusion than is an absolute voltage threshold for the ST
segment.44 The present study required at least a 75%
reduction in the maximum ST elevation as a marker of reperfusion,
similar to that previously used by our group.21 Other
investigators, using serial 12-lead ECGs rather than continuous ST
monitoring, have employed thresholds of 20% to 50% reduction in
maximum ST elevation.44 45 A threshold of a 75%
reduction
in ST elevation may be less sensitive but will be more specific as a
marker of reperfusion. Most patients exhibited a rapid and profound
reduction in ST elevation at the time of reperfusion (see Fig
1). In
these patients, the differences in ischemia time, calculated by
a threshold of 50% or 75% reduction in ST elevation, would be small.
A few patients who had a more gradual decline in ST elevation may have
had some overestimation of ischemia time with the present
threshold, but it should be noted that these patients clearly exhibited
prolonged ST elevation.
Measurement of Infarct Size
Measurement of infarct size in
humans is difficult, the two
principal techniques being electrocardiography
and radionuclide imaging. The present study used the Selvester QRS
score, which was originally derived from computer modeling of the ECG.
This score has subsequently been validated against anatomic
measurements of infarct size29 30 and has also been
correlated with the degree of impairment of left ventricular systolic
function after infarction.46 To validate the use of the
QRS score for estimating the extent of the ischemic risk region
and subsequent infarct size, we previously compared the QRS
measurements with radionuclide measurements of the risk region and
infarct size (C. Juergens et al, unpublished observations). The QRS
measurements of the risk region in this study were 12% to 51% of the
left ventricle, with a few patients having very large risk regions of
70% of the ventricle. These findings are comparable to our previous
radionuclide findings47 and to those of other
investigators.8 47 48 49
ECG measurements must contend with the variable relations between epicardial and skin surface potentials, according to body habitus. The presence of Q waves does not always mean complete infarction,50 but the QRS score makes some allowance for this by weighting lead scores according to size of Q-wave and R- and S-wave amplitudes. Within the individual, errors due to body habitus are likely to be common to the QRS measurements of risk region and infarct size. Such errors will largely cancel out in the calculation of infarct/risk ratio, which is the important outcome variable related to duration and severity of ischemia.
Ischemia Time and Myocardial Function
Despite restoration of
coronary blood flow, the
postischemic myocardium exhibits delayed recovery of
contractile function. This phenomenon of myocardial stunning has been
well documented in animal studies51 and has been described
in humans after both regional and global
ischemia.10 Experimental data indicate that the
severity and duration of ischemia are important determinants of
the degree of myocardial stunning.51 Our findings show
that, in humans, ischemia time is also an important determinant
of subsequent contractile dysfunction, and these findings are
concordant with the QRS score results. Previous studies in humans have
suggested that contractile function recovers over a period of 7 to 14
days after ischemia.18 52 Our data show that the
rate of recovery of contractile function is variable and is inversely
related to the duration of the ischemic insult. Patients with
short (<3 hours) ischemia times have largely recovered
function by the time of hospital discharge. Patients with more
prolonged ischemia (6 to 9 hours) still exhibit some functional
improvement but may not do so for up to 1 month after the
ischemic event. This knowledge of the natural history of
myocardial stunning in humans can guide the clinician's decisions
regarding further intervention in patients with persistent wall motion
defects after ischemia. In addition, these findings could
provide a baseline reference for future investigations of adjunctive
therapy, such as oxygen free radical scavengers, aimed at ameliorating
myocardial stunning in humans.
Clinical Implications
The likely relation between ischemia
time and myocardial
salvage has been emphasized by Gersh and Anderson.53 The
present study clearly demonstrates this relation, and the findings
have important clinical implications. The multivariate
regression models developed in this study may be used to predict
infarct size in the individual patient. The accuracy of predicted
absolute infarct size is approximately ±7% in 95% of patients.
Prediction of the infarct/risk ratio is less accurate, because in
patients with small infarcts, the model tends to overestimate infarct
size.
The two predictors identified in this study that can be manipulated by the physician are heart rate and duration of ischemia. The role of heart rate as a determinant of infarct size is consistent with experimental data and with the results of trials of early ß-adrenergic blocker treatment in acute infarction.54 The duration of ischemia is the most important factor amenable to intervention. Intravenous thrombolytic therapy is the initial treatment for myocardial infarction in most centers, but the rate of reperfusion of the infarct artery is only 54% to 60% at 90 minutes in patients given streptokinase and up to 81% in patients given accelerated tissue-type plasminogen activator.55 The importance of ischemia time is highlighted by recent therapeutic trials. The GUSTO study showed that earlier patency of the infarct artery was associated with a better clinical outcome.55 56 Similarly, studies of primary angioplasty in acute infarction have shown that reduction in ischemia time is associated with a better patient outcome.57 58 In contrast, when thrombolytic therapy and angioplasty were associated with similar ischemia times, clinical outcome was not improved by angioplasty.59 Although routine angioplasty after thrombolytic therapy does not appear to improve patient outcome,60 angioplasty in high-risk patients who fail to reperfuse after thrombolytic therapy may be helpful,61 if prolonged ischemia times can be prevented.
Continuous ST monitoring allows measurement of ischemia time and detection of reperfusion. Other variables, including extent and degree of ST-segment elevation, allow the physician to decide how much myocardium is likely to be at risk and the degree of urgency required to establish reperfusion of the infarct artery. Patients with marked and extensive ST elevation are in greatest need of early reperfusion, which may be better achieved by immediate angioplasty. Similarly, those patients who exhibit persistent ST elevation after thrombolytic therapy may do well to undergo rescue angioplasty, according to the extent or severity of ST-segment elevation. In contrast, patients who have rapid resolution of ST elevation or only limited persistent ST elevation would probably not need early angioplasty.
Conclusions
The duration of ischemia is the most important
determinant of infarct size and subsequent recovery of myocardial
function in humans. The application of continuous ST-segment monitoring
allows detection of reperfusion of the infarct artery, documentation of
ischemia time, and prediction of subsequent injury to the
heart. The management of patients with acute myocardial infarction may
therefore be improved by the use of continuous ST-segment monitoring to
guide thrombolytic therapy and other interventions such as early
angioplasty.
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Acknowledgments |
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This study was supported by grants from the National Health and Medical Research Council (917715) and the Clive and Vera Ramaciotti Foundation (N224) to Dr Jeremy and by the Medical Foundation of the University of Sydney. Dr Hasche was the recipient of a Postgraduate Research Scholarship from the National Heart Foundation of Australia. The authors gratefully acknowledge the assistance of Vijay Solanki and Krishna Kathir in analysis of the ECGs and the secretarial assistance of Yvonne Johnstone.
Received December 15, 1994; accepted February 7, 1995.
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References |
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TopAbstractIntroductionMethods Results Discussion References |
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