J R Soc Med 2004;97:566-570
doi:10.1258/jrsm.97.12.566
© 2004 Royal Society of Medicine
Clinical implications of ST-segment non-resolution after thrombolysis for myocardial infarction
L Bhatia BSc MRCP
G J Clesham PhD FRCP
D R Turner BSc FRCP
Cardiac Department, Broomfield Hospital, Court Road, Chelmsford, Essex
CM1 7ET, UK
Correspondence to: Dr L Bhatia, 5 The Windmills, Broomfield, Chelmsford, Essex
CM1 7HL, UK E-mail:
lokebhatia{at}aol.com
 |
SUMMARY
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Failed reperfusion after thrombolytic therapy for acute myocardial
infarction
is common and signifies a poor prognosis. We investigated the
clinical
consequences of non-resolution of the ST segment after thrombolytic
therapy
for acute ST-elevation myocardial infarction, in 85 consecutive
patients
admitted to a coronary care unit lacking rapid access to angioplasty.
Failed
thrombolysis was defined as <50% ST-segment resolution 180
minutes
after the start of thrombolytic treatment. Outcomes
were measured in terms of
in-hospital adverse events, length
of hospital stay, and mortality at 6 weeks
and 1 year.
Thrombolysis was successful, in terms of ST-segment resolution, in 45
patients (53%). After adjustment for other factors, ST resolution was the only
independent predictor of an uncomplicated recovery in hospital (odds ratio
6.8, 95% confidence interval 2.3 to 19.9; P<0.001). At 6 weeks and 1 year,
overall mortality was lower in the ST resolution group, though these
differences became non-significant on multivariate analysis. In patients who
survived to hospital discharge, median length of stay was greater in
successfully thrombolysed patients (9 days versus 8 days) despite their lower
rate of complications.
ST-segment resolution is a useful marker of successful thrombolysis and
relates to clinical outcome. If assessed routinely it might assist, along with
other clinical markers, in the identification of low-risk patients who can be
discharged early.
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INTRODUCTION
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Thrombolytic therapy for acute myocardial infarction reduces
case fatality
and improves clinical
outcomes.
1,2
However, in
up to 60% of patients the treatment does not restore perfusion
in
the myocardium at
risk
3 and such
failure indicates a worse
prognosis.
4 In the
past, reperfusion was commonly assessed in terms of coronary
blood flow,
achievement of TIMI 3 flow being a favourable
sign;
5 however, this
angiographic index is not a reliable indicator
of myocardial reperfusion,
which is prognostically more relevant
than coronary
reperfusion.
6,7
By contrast, ST-segment resolution
90–180 minutes after thrombolysis is
an excellent marker
of successful myocardial
reperfusion
8 and a
strong predictor
of survival and preservation of left ventricular
function.
9–11
In
the UK this simple bedside tool tends to be neglected as an
indicator of
prognosis or guide to further
management.
12
Decisions
on matters such as length of hospital stay and selection for
angiography
or treadmill investigation are determined mainly by in-hospital
clinical
events or
age.
13 Currently in
the UK, most district general
hospitals lack rapid access to angioplasty and
must rely solely
on thrombolytic therapy in the first instance. In an
observational
study of unselected patients we investigated the short-term
and
long-term implications of ST-segment non-resolution after
thrombolytic
therapy.
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METHODS
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Patients
In the course of seven months, 104 consecutive patients received
thrombolytic
therapy for suspected ST-elevation myocardial infarction, in
the
coronary care unit of a district general hospital that lacked
rapid access to
coronary angioplasty. All had a history of typical
precordial pain at rest
lasting >20 minutes as well as ST
elevation in two or more contiguous leads
on a standard 12-lead
electrocardiogram (0.1 mV limb leads, 0.2 mV precordial
leads)
or left bundle branch block. Conventional contraindications
to
thrombolysis were observed and streptokinase or alteplase
was administered
according to local guidelines. Creatine kinase
and troponin-I were measured 12
hours after admission and our
final analysis was confined to patients who
showed an increase
in creatine kinase to twice the upper limit of normal and
an
increase in troponin-I (>99% centile). 13 patients were excluded
on this
basis.
Electrocardiographic analysis
A baseline 12-lead electrocardiogram was recorded before initiation of
thrombolysis and at 90 and 180 minutes thereafter. The lead with maximum ST
segment elevation in the initial record was used for comparison. ST segments
were measured by caliper at 60 ms beyond the J-point, retrospectively by a
single independent observer blinded to clinical outcomes. Anterior infarction
was recorded when maximum ST elevation involved leads V1–V4. Successful
thrombolysis was taken as >50% resolution of the worst ST segment at 180
minutes. If the 180-minute electrocardiogram was not available (for example,
because of earlier death), then the 90-minute record was used (8% of analysed
patients). A further 6 patients with left bundle branch block were excluded,
leaving 85 patients for the final analysis.
Data collection
Clinical details were recorded prospectively. In-hospital major adverse
events were defined as the occurrence of any of the following: death,
reinfarction (defined as two out of three of chest pain, further ST elevation
or further cardiac enzyme increase), stroke, cardiogenic shock, hypotension
(systolic <90 mmHg), Killip class II–IV, recurrent angina or
ischaemia, significant arrhythmias or major bleeds. Adverse events were
divided according to timing—days 1–3 (i.e. <72 h) and days
4–7. An uncomplicated course was defined as no major adverse event
during the entire inpatient stay.
Out-of-hospital clinical outcomes at 6 weeks were all-cause mortality and
morbidity (reinfarction, stroke or cardiac readmission without enzyme rise),
determined at routine clinic visit, by review of the case notes or by contact
with the general practitioner. At 1 year, only mortality was assessed.
Follow-up was complete in all patients included in the final analysis.
Statistical analysis
For statistical analysis we used SPSS 11.5 for Windows. Differences between
groups were evaluated by 
2 and Fisher's exact test for
categorical variables and by unpaired Student's t test for
continuous variables. Spearman's rank correlation analysis was used to
investigate the relation between non-parametric variables. Multivariate
logistic regression was used to test associations between pre-determined
variables and outcomes. Values were specified as probability values
(P) or odds ratio (OR) with 95% confidence intervals (CI). A
P value of <0.05 was taken as significant.
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RESULTS
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Of the 85 patients included in the analysis, 45 (53%) showed
ST-segment
resolution.
Table 1 summarizes
the ST-segment results
in relation to baseline characteristics. In a
multivariate analysis,
the only difference that approached significance was
pain to
needle time (
P=0.06). Age was not an independent predictor of
ST-segment
non-resolution.
Figure 1 shows the
difference in adverse events between the groups with successful and
unsuccessful thrombolysis. The patients with ST-segment non-resolution had
more than twice the rate of adverse events during the first 72 hours. The most
striking difference was in the proportions of patients who had an
uncomplicated in-hospital stay— 62% of the ST-resolution group compared
with 17% of the non-resolution group (P<0.001).
Another important finding was that, irrespective of the
electrocardiographic outcome of thrombolytic therapy, late (day 4–7)
inpatient adverse events were always preceded by early (day 1–3) events;
in other words, any patient who did not experience an early adverse event
remained event-free throughout his or her in-hospital stay.
In a multivariate analysis including age, pain to needle time, diabetes and
previous myocardial infarction, only ST resolution proved to be a significant
predictor of an uncomplicated recovery throughout the hospital stay (adjusted
OR 6.8, 95% CI 2.3 to 19.9, P<0.001).
Length of stay was calculated only in patients who survived to hospital
discharge, and we excluded any inpatient transfers to our tertiary centre. Any
'social' days (i.e. awaiting placements or social work-up) which
delayed discharge were also omitted from the analysis. With these exclusions,
overall median length of hospital stay was one day greater in the successfully
thrombolysed group (9 days versus 8 days).
At 6 weeks, 13 (15%) of the entire cohort had died, 12 of whom were from
the failed thrombolysis group. Table
2 shows the predictors of 6-week mortality, of which only pain to
needle time was significant on multivariate analysis (adjusted OR 0.996, 95%
CI 0.993 to 0.999, P=0.02); ST non-resolution was just short of
statistical significance (adjusted OR 0.12, 95% CI 0.12 to 1.28,
P=0.07). There was no significant difference in 6-week morbidity
after hospital discharge, with 3 (7%) successful compared with 4 (10%) failed
cases experiencing the combined endpoint of reinfarction (2), stroke (0) or
cardiac readmission (5).
Overall, the number of deaths at 1 year was 15 (18%), 13 from the
ST-non-resolution group. In a multivariate analysis, age was the only
significant predictor of 1-year mortality (adjusted OR 0.89, 95% CI 0.80 to
0.99, P=0.03); pain to needle time (P=0.08) and ST
resolution (P=0.10) showed only a trend.
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DISCUSSION
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This study highlights the poor clinical outcome of patients
with ST-segment
non-resolution after thrombolytic treatment,
indicated by simple evaluation of
the post-thrombolysis electrocardiogram.
In this series from a district
general hospital, ST resolution
was the only independent predictor of an
event-free recovery
in hospital. Although previous studies have demonstrated
that
older age, female gender and cardiac risk factors such as diabetes
and
hypertension are associated with an increase in inpatient
cardiac events after
a myocardial
infarction,
14,15
these studies
did not incorporate differences in ST-segment resolution after
thrombolysis.
The average length of stay in our hospital for all patients was 8 days,
which is comparable with the UK national average of 9
days.16 However, an
unexpected finding was that patients with successful thrombolysis spent one
day longer in hospital compared to failed cases, which is well over the
current European Society of Cardiology recommendations of 4 to 5
days17 for patients
with uncomplicated infarction. We did not investigate the reasons for the
discrepant finding in our series, but it could have been related to lack of
senior staff on certain days or weekends to sanction early
discharge.18
Some limitations of the study should be mentioned here. First, the ST
segment after acute myocardial infarction is dynamic, and our use of static
measurements could have led to errors in labelling of patients as successful
or failed reperfusion. Our aim, however, was to obtain results relevant to
typical coronary care units across the UK, few of which can monitor the ST
segment continuously in every patient. Secondly, the small size of our sample
increases the likelihood of type 1 or 2 errors. Moreover, the results do not
translate to patients with bundle branch block or other electrocardiographic
features where ST segment resolution cannot be determined.
What are the practical implications of our findings? The most obvious is
the potential utility of ST-segment resolution for deciding which patients can
safely be discharged early. Not only did the patients with ST resolution have
a 3 to 4-fold greater rate of uncomplicated recovery than those with
non-resolution; we also observed that, irrespective of ST-resolution outcome,
patients who did not experience an adverse event in the first 72 hours after
admission remained event-free subsequently while in hospital. Previous workers
have likewise shown that most of the adverse events after myocardial
infarction occur in the first 48–72
hours.19
Combination of these observations— ST resolution as a predictor of
clinical outcome, coupled with freedom from complications early in the
hospital stay—might allow safe discharge as early as 3–4
days.20 In our
study, exactly one-third of the patients would have come into this category,
potentially translating into large savings in cost and bed space, to say
nothing of improved patient satisfaction. However, this strategy should
ideally be assessed in a large prospective trial.
What can be said of the patients in whom thrombolysis fails to restore
myocardial reperfusion? The current management options are repeat
thrombolysis, rescue angioplasty and stenting, and use of glycoprotein
IIb/IIIa inhibitors. Regarding repeat thrombolysis, we are short of evidence.
In 37 patients with ST-segment non-resolution 90 minutes after streptokinase,
Mounsey et
al.21 compared
alteplase with placebo and found it better in terms of infarct sizes and left
ventricular function; however, benefit was seen only in patients who had
failed to reach a lytic state with high plasma fibrinogen levels after initial
streptokinase. In patients with failed thrombolysis and cardiogenic shock,
there is substantial evidence in favour of rescue percutaneous coronary
intervention.22,23
It is the more clinically stable group, with failed thrombolysis but no
ongoing ischaemic symptoms, in whom subsequent management is more debatable.
In older trials a rescue strategy seemed no better than conservative treatment
in terms of subsequent
death.24 Hopes were
then pinned on stents and glycoprotein IIb/IIIa inhibitors, but the recently
published MERLIN
trial,25 in which
307 patients with failed thrombolysis (based on ST non-resolution) were
randomized to percutaneous coronary intervention or conservative treatment,
showed no advantage for the rescue therapy in terms of either 30-day mortality
or left ventricular function. Furthermore, rescue therapy was associated with
more strokes and major haemorrhage; the only benefit was a reduction in
subsequent revascularization. Therefore, rescue percutaneous coronary
intervention cannot be recommended as routine treatment after failed
thrombolysis. Regarding glycoprotein IIb/IIIa inhibitors, the major drawback
of these agents is the risk of bleeding
complications.26,27
Although in combination with thrombolytics they give better reperfusion than
thrombolytics
alone,28 this does
not seem to translate into mortality
benefit.29,30
Thus at present there is no obvious way to improve clinical outcomes after
failed thrombolysis.
From this study we conclude that routine evaluation of ST-segment
resolution after thrombolysis for myocardial infarction, coupled with other
clinical markers, might facilitate selection of patients who can safely be
discharged early.
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Acknowledgments
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We thank Dr S Subramonia-Iyer for statistical advice and Fiona
Robinson,
Angela Richardson and all coronary care unit staff
for help with the
collection of data.
|
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SUMMARY
INTRODUCTION
successful; 
failed