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Medicent Electron. 2022 Oct.-Dec.;26(4)

Original article

Prognostic factors for thrombolysis failure in patients with

diagnosis of acute myocardial infarction
Prognostic factors of thrombolytic failure in patients diagnosed with acute
myocardial infarction

Hector Palacio Perez1*https://orcid.org/0000-0003-0592-4555 Karina

Beatriz Rey Garcia1https://orcid.org/0000-0002-4684-5741 Jose Julian
Castillo Cuello1https://orcid.org/0000-0001-9387-3457

1University of Medical Sciences of Havana. Clinical-Surgical Teaching Hospital "Joaquín

Albarrán", Havana. Cuba.

* Corresponding author: Email:hector.palacio@infomed.sld.cu

SUMMARY
Introduction:The most important therapeutic measure in patients with acute
myocardial infarction with ST-segment elevation is reperfusion of the ischemic territory;
fibrinolysis is the primary strategy in many hospitals. Early diagnosis of those patients at
risk of thrombolysis failure is vital.
Aim:To identify the prognostic factors for thrombolysis failure in patients diagnosed
with ST-segment elevation acute myocardial infarction. Methods:Descriptive and
prospective study that included patients treated in the Emergency Department of the
"Joaquín Albarrán" Clinical-Surgical Hospital, diagnosed with the aforementioned
disease, and treated with recombinant streptokinase, among
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November 2018 to May 2020. 66 patients were included in the research. The variables
analyzed were: age, sex, arterial hypertension, diabetes mellitus, time between the
onset of symptoms and the onset of fibrinolysis, location of the infarct, duration of the
QRS complex, duration, and depth of the wave.
Results:There was thrombolysis failure in 27 patients (40.9%). The variables: time of
thrombolysis, duration and depth of the Q wave, as well as the duration of the QRS
showed values with significant differences between both groups (p<0.05). The
multivariate analysis confirmed the duration and depth of the Q wave as independent
factors, predictors of thrombolysis failure: (OR= 14.50; 95% CI 1.58-132.33); (OR: 1.69;
95% CI 1.27-2.26), respectively.
Conclusions:The analysis of the depth and duration of the Q wave in the initial
electrocardiogram of the patients studied allows us to predict a subpopulation of
patients at risk of thrombolysis failure.
DeCS:myocardial infarction; streptokinase; thrombolytic therapy.

ABSTRACT
Introduction:the most important therapeutic measure in patients with ST-segment
elevation acute myocardial infarction is reperfusion of the ischemic territory; fibrinolysis is
the primary strategy in many hospitals. Early diagnosis of those patients with risk of failed
thrombolysis is vital.
Target:to identify prognostic factors of thrombolytic failure in patients diagnosed with ST-
segment elevation acute myocardial infarction.
methods:a descriptive and prospective study including patients treated in the
Emergency department at "Joaquín Albarrán" Clinical and Surgical Hospital, who were
diagnosed with the previously mentioned disease and treated with recombinant
streptokinase, between November 2018 and May 2020. A number of 66 patients were
included in the investigation. Age, gender, arterial hypertension, diabetes mellitus, time
between onset of symptoms and onset of fibrinolysis, location of the infarction, QRS
complex duration, duration and depth of the wave were the variables analyzed.

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Results:thrombolysis failed in 27 patients (40.9%). Time of performing thrombolysis,

duration and depth of the Q wave, as well as the QRS duration showed values with
significant differences between both groups (p<0.05). The multivariate analysis confirmed
the duration and depth of the Q wave as independent factors, predictors of thrombolysis
failure: (OR= 14.50; 95% CI 1.58-132.33); (OR: 1.69; 95% CI 1.27-2.26), respectively.
Conclusions:the analysis of the depth and duration of the Q wave in the initial
electrocardiogram of the studied patients allows us to predict a subpopulation of patients
with risk of failed thrombolysis.
MeSH:myocardial infarction; streptokinase; thrombolytic therapy.

Received: 02/10/2021
Approved: 07/11/2022

INTRODUCTION
The therapeutic measure with the greatest positive impact on the prognosis of patients
with ST-segment elevation acute myocardial infarction (STEMI) is reperfusion of the
ischemic territory, which should be performed in the shortest possible time, depending
on the selected strategy.(1)
In this sense, early percutaneous coronary intervention (PCI) (<90 minutes from the first
medical contact) is the treatment of choice in centers with the capacity to perform it, it is
associated with better results in terms of reperfusion of the responsible artery and long-
term survival.(1)However, when it cannot be performed before 120 minutes, fibrinolytic
therapy should be given, followed by transfer to a PCI-capable institution.(1)Fibrinolysis is
the thing to do in many hospitals in developing countries(2)where there is no immediate
capacity to perform PCI, therefore, it is the alternative used at the "Joaquín Albarrán
Domínguez" Clinical-Surgical Hospital, which treats a

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population of 437,102 inhabitants and located in Havana, province of Cuba, which has a
crude rate of heart disease of 300.9 per 100,000 inhabitants.(3)
So, it is clear that in the world,(2)and especially in our country, there is a population
whose survival improvements depend on the success of the reperfusion of the artery
related to the infarction, through a strategy focused on the use of fibrinolytics. Early
recognition, using a non-invasive, simple, and reliable technique, of individuals who may
have failed reperfusion with fibrinolytics is vital, as they are at greater risk of developing
cardiogenic shock, severe heart failure, lethal arrhythmias, or sudden death. .

In order to identify the predictive factors of thrombolysis failure in patients diagnosed

with STEMI in the period from November 2018 to May 2020, it was decided to carry out
this investigation.

METHODS
A descriptive and prospective study was carried out, which included all the patients who
were treated in the Emergency Department of the "Joaquín Albarrán Domínguez"
Clinical-Surgical Hospital with a diagnosis of STEMI and who, once contraindications had
been ruled out, were treated with intravenous fibrinolysis in the period from November
2018 to May 2020. Excluded from the research were those who presented an image of
left bundle branch block in the initial electrocardiogram, presumably of a new
appearance, and those with pacemakers. The clinical variables considered were: age,
sex, arterial hypertension, diabetes mellitus, time elapsed between the onset of
symptoms and the onset of fibrinolysis. The electrocardiographic parameters analyzed
were: Location of the AMI ST,

For the diagnosis of STEMI, the criteria of the World Health Organization were used, the
patient had to present two of the following three criteria: Typical pain of more than 30
minutes; new ST-segment elevation ≥ 1 mm (0.1 mv) in two or
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more contiguous leads, in leads V2-V3 ≥2mm (0.2mv) in men and ≥1.5mm (0.15mv) in
women. Increase in blood of sensitive and specific markers of myocardial necrosis
(cardiac troponins, the CPK-MB fraction (CPK-MB, or both).(4)

Once the diagnosis was confirmed, the patients were admitted to the Special Intensive
Care Unit, located in the Emergency Department of the hospital. Physiological variables:
blood pressure, heart rate and rhythm, as well as respiratory rate and oxygen
saturation, were continuously monitored using a pulsometer. Fibrinolysis was
performed with recombinant streptokinase (the only fibrinolytic used in our hospital) at
a standard dose of one million five hundred thousand units diluted in 100 milliliters of
physiological saline solution, to be administered in one hour, using syringes or
perfusion pumps, suitably regulated. . All patients underwent serial electrocardiograms,
the frequency of which was defined by the attending physician,

ST segment displacement was measured 80 milliseconds from the J point, using a

standard ruler graduated in millimeters. Thrombolysis failure was considered if at 90
minutes there was no reduction of at least 50% in ST segment displacement.

The duration of the QRS was considered from the beginning of the Q wave to the J point
of the ST segment, by means of a magnifying glass three consecutive beats were
measured and their value was averaged, in the same way the measurement of the Q
wave, both in duration and in depth.

Ethical Considerations:
This study was approved by the Scientific Council and the Ethics Committee of the
"Joaquín Albarrán" Clinical-Surgical Hospital. The consent of the patient and the
companions was requested, orally and in writing.

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Statistics:
Initially, in the qualitative variables, the statistical technique of frequency distribution
analysis was used; For each of the categories, the absolute and relative frequencies
(percentages) were calculated, and in the case of quantitative variables, the mean and
standard deviation were calculated. To identify the possible predictors of thrombolysis
failure in the qualitative variables, the homogeneity test was used (Chi-square without
correction and with correction for continuity), and in the quantitative variables the non-
parametric Wilcoxon-Mann-Whitney test was used. . For these hypothesis tests that
were performed, a significance level α = 0.05 was set.

In a second stage, to evaluate each of the variables, independently, as possible

predictors of thrombolysis failure, controlling the effect of the others, logistic regression
was used. A collinearity analysis was performed beforehand to prevent the variables
included in the model from having a high degree of association, and a variable was
considered to be a prognostic of thrombolysis failure, when the confidence interval
calculated for itsodds ratio(eβi) did not include unity.

RESULTS
A total of 66 patients were included in the investigation; the average age was 59-70
years; there was a predominance of the male sex (72.7%); the mean time between the
onset of pain and the performance of thrombolysis was 5.35 hours; most of the patients
had a lower localized infarction (56.1%); Of the total number of patients, 52 underwent
thrombolysis before six hours and the procedure was effective in 37 (71.15%), while in
14 patients the treatment was performed after six hours and its efficacy decreased to
14. .28%. In general, there was thrombolysis failure in 27 patients (40.9%).

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Comparatively, and from the electrocardiographic point of view, the patients with
thrombolysis failure showed, on average, a longer duration and depth of the Q wave,
as well as a wider QRS complex. (Table 1 ).

Table 1.Patients with a diagnosis of acute myocardial infarction, according to clinical parameters-

electrocardiographic and thrombolysis results.

Clinical Parameters failure of success of Total p-value
thrombolysis thrombolysis
Age (Average in years) 60.63±7.34 59.05±7.82 59.70±7.61 0.714
Sex 0.230
Male 17 (35.41) 31 (64.58) 48 (100)
Female 10 (55.55) 8 (44.44) 18 (100)
Personal medical history
Mellitus diabetes 5 (41.66) 7 (58.33) 12 (100) 1,000
Arterial hypertension 19 (42.22) 26 (57.77) 45 (100) 0.961
Location 0.748
Former 13 (44.82) 16 (55.17) 29 (100)
lower 14 (37.83) 23 (62.16) 37 (100)
thrombolysis time 0.004*
Thrombolysis within 6 h 15 (28.84) 37 (71.15) 52 (100)
Thrombolysis equal to or greater than 6 h 12 (85.71) 2 (14.28) 14 (100)
electrocardiographic parameters
Q wave duration (msec). 39.44 ± 5.064 30.00 ±2.294 33.86±5.93 0,000*
Q wave depth (mm) 2.48 ± 0.509 1.87±0.522 2.12±0.59 0,000*
QRS complex duration (msec). 90.56 ±6.091 86.62 ± 6.524 89.50±6.94 0.006*
* Significant value of p (p< 0.05. h: hours. msec: milliseconds. mm: millimeters.

A first statistical analysis showed that of the variables analyzed, the thrombolysis time,
the duration and depth of the Q wave, as well as the duration of the QRS showed values
in which there were significant differences between both groups (p<0.05 ).

In order to independently identify the predictive variables of thrombolysis failure, a

multivariate analysis (logistic regression) was performed that included the following
parameters: Q wave duration and depth, QRS duration, and thrombolysis time. In
accordance with this model, the duration and depth of the Q wave were confirmed as
independent predictor variables of failure of
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thrombolysis, since for each mm of increase in its depth the probability of failure
increased more than 14 times (OR= 14.50; 95% CI 1.58-132.33); while for each msec
increase in its duration, the probability of failure increased by more than one and a half
times (OR: 1.69; 95% CI 1.27-2.26). (Table 2 ).

Table 2.Odds ratio, 95% CI, thrombolysis failure, estimated by logistic regression.
variables OR 95% CI p-value
QRS Duration (msec) 0.98 0.81-1.18 0.87
thrombolysis time 1.98 0.98-3.97 0.05
Q wave duration (msec) 1.69 1.27-2.26 0.00
Q wave depth (mm) 14.50 1.58-132.33 0.01
msec: milliseconds. mm: millimeters. OR:odd ratio. CI: confidence interval.

DISCUSSION
One of the main objectives of the treatment of patients suffering from STEMI is to
achieve reperfusion of the affected vessel; fibrinolysis is an alternative for those patients
in whom PCI cannot be performed. However, it is highly recommended to identify early
those patients with probabilities of thrombolysis failure; ST segment resolution analysis
offers an easy and reliable way to assess the efficacy of the procedure.(5)

In the present study, the thrombolysis failure rate, based on electrocardiographic

criteria, was 40.9%, which is in line with what was reported by other authors.

In the GUSTO-I study (Global Utilization of Streptokinase and Tissue Plasminogen

Activator for occluded Coronary Arteries), which evaluated different strategies with
thrombolysis and included 41,021 patients, failure with streptokinase was 46%.(6)In
another more recent study involving 243 patients, failure was found in 38.6%.(7)
There are several factors that are consistently analyzed as predictors of thrombolysis
failure, among which are: Sex, location of the infarct and cardiovascular risk factors,
such as diabetes mellitus and arterial hypertension.(8,9)In
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The present investigation did not find that these parameters were related to the success
or failure of the procedure.
The benefits of early use of fibrinolysis are well documented, which is why it is highly
recommended to perform the procedure in the pre-hospital setting (time dependent),
which is associated with a reduction in early mortality of up to 17%.(1)

In this study, 14 patients underwent late thrombolysis (after 6 hours), of which 12 were
considered unsuccessful. Despite this result, and after performing a logistic regression
analysis, this indicator was ruled out as an independent predictor of thrombolysis
failure.
In daily practice, once an STEMI has been diagnosed, the duration of the QRS complex,
as it does not constitute a diagnostic criterion, is not taken into account when faced with
ST-segment elevation. However, there are several works where QRS widening is related
(without bundle branch block criteria)(10,11)as a predictor of thrombolysis failure,
ventricular dysfunction and sudden death. And it is that the phenomenon is associated
with a delay in intraventricular conduction, secondary to significant myocardial
ischemia. Despite this, this study did not demonstrate QRS widening as an independent
factor of thrombolysis failure.
Traditionally, the appearance of the Q wave has been related to irreversible myocardial
damage. The presence of a well-organized clot makes it less likely to occur after the use
of streptokinase; additionally, its presence has been related as an independent factor of
heart failure, cardiogenic shock, and mortality in the first 30 days after the infarction.
(12,13,14)In this sense, these results confirmed the appearance of the Q wave as an
independent factor of thrombolysis failure.

Mostafavi-Toroghi,(fifteen)evaluated 143 patients with a diagnosis of STEMI and found that

those with a Q wave were at risk of thrombolysis failure, regardless of the time it was
performed, thus concluding that in patients

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In patients with Q waves in their initial electrocardiogram, primary PCI was

recommended and not thrombolysis.
However, in our opinion, the presence of a Q wave (in the context of our hospital,
without the capacity to perform primary PCI), gives us the possibility of identifying a
subgroup of patients that we should not deprive of the potential benefits of early use of
fibrinolytics, and in whom, at the same time, emergency transfer to a PCI-capable center
should be considered, once fibrinolysis is complete, perhaps with priority over other
patient subpopulations.

CONCLUSIONS
Analysis of the depth and duration of the Q wave in the initial electrocardiogram of
patients diagnosed with ST-segment elevation acute myocardial infarction allows us to
easily and quickly predict a subpopulation of patients at risk of heart failure.
thrombolysis.

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Conflicts of interest

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The authors declare not to have any interest conflicts

Author contribution
Conceptualization:Hector Palacio Perez.
Design and organization of the study, literature search, sample selection, primary
data collection, data analysis, preparation and writing of the manuscript,
statistical processing:Hector Palacio Perez, Karina Beatriz Rey Garcia.

Literature search, data analysis, preparation, writing and approval of the

manuscript, statistical processing:José Julián Castillo Cuello. Sources of funding:The
authors declare that they have no source of funding.

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