PREDICTORS OF FAILED THROMBOLYSIS IN ACUTE MYOCARDIAL INFARCTION

Background & objectives: Acute myocardial infarction (AMI) is becoming increasingly important problem in developing countries, and thrombolysis is the main modality of treatment here. About 2550% of patients fail to achieve successful reperfusion and these patients have poor prognosis. Since alternative modes of reperfusion are available, it is important to identify them. This study was aimed at defining the extent of failed thrombolysis and identifying its demographic and clinical predictors Methods: 50 cases of thrombolysed AMI patients were studied. Failed thrombolysis considered if there is < 50% resolution of ST-segment elevation after 90minutes of thrombolysis in single lead showing maximum ST elevation at presentation. The clinical predictors of the outcome were assessed. Results: Of 50 patients studied 30(60%) achieved successful thrombolysis and 20(40%) failed. Mean time to thrombolysis from onset of symptom was 5.85 ±2.49 hrs in failed group v/s 4.55 ±2.4hrs in successful group (P<0.05).Mean age was 52.3±11.14yrs v/s 57.4±12.5yrs (P>0.05), percentage of females was 25% v/s 16.7%(P>0.05), mean time for resolution of chest pain was 3.55±1.1 hrs v/s. 1.98±0.93 hrs (P<0.001), percentage of anterior MI was 70% v/s 53% (P>0.05), inferior wall MI was 30% v/s 46% (P>0.05) in failed and successful group respectively. Interpretation and conclusion: Late presentation is an important risk factor for failed thrombolysis in AMI. Persistence of chest pain and non-resolution of reciprocal ST depression are significantly associated with failed thrombolysis


Introduction
Acute myocardial infarction is one of the most common diagnoses in hospitatised patients in industrialized countries. 1 Despite the impressive strides in diagnosis and management over the past three decades, acute myocardial infarction continues to be a major health problem in industrialized world and is becoming and increasingly important problem in developing countries. 2 Because acute myocardial infarction strikes an individual during the most productive years, it can have profoundly deleterious psychological and economic ramification. 2 The unequivocal demonstration of role of the thrombus in acute myocardial infarction quickly led to the systematic testing of thrombolytic strategies to abort myocardial infarctions. 3 The thrombolytic therapy is the main mode of reperfusion in developing countries like India. 3 Although 60 to 70% of treated patients can be successfully reperfused, thrombolytic treatment fails in a substantial proportion. These non-responsive patients can have a significant high mortality and morbidity. Since alternative modes of coronary intervention are available, it is prudent to identify patients with failed thrombolysis so that they can be offered alternative modes of reperfusion. 4 The present study is aimed at defining the extent of failed thrombolysis and assessing its demographic and clinical predictors in our hospital. Though the study was done some years back the demographic and clinical picture are still the same, hence the results are much relevant.

Results
Based on ECG Criteria 30 patients (60%) had successful thrombolysis and 20(40%) had failed thrombolysis. Mean age of patients was more in failed thrombolysis (57.4±12.5) than in patients with successful thrombolysis (52.3±11.14), but it was statistically not significant. Failed group had higher percentage of patient in age group > 70 yrs but it was statistically not significant.
Though the percentage of females in failed group was higher (25% v/s 16.7%) it was statistically not significant. Risk factors for coronary heart disease: The percentage of patients with diabetes, hypertension and dyslipidemia was higher in failed thrombolysis group. The percentage of smokers and patients with BMI >23 was higher in successful group. All the above observations were statistically not significant. Time to thrombolysis from onset of symptoms: The mean time to thrombolysis from the onset of symptoms was significantly high in patients with failed thrombolysis. Patients presenting within 3 hrs of symptoms had a strong trend towards successful thrombolysis though statistically not significant. Heart rate and blood pressure: The distribution of patients according to those having tachycardia normal heart rate, bradycardia or systolic BP was almost similar in two groups. Killip class at presentation: In failed group 16 patients (80%) had Killip class-I at presentation and in successful group 25 patients (83.3%). Killip class > I was seen in 4 patients (20%) in failed group, and in 5 patients (16.7%) in successful group. This was statistically not significant. Site of Myocardial Infarction: In failed thrombolysis group 14 patients (70%) had anterior wall MI and 6 patients (30%) had non anterior MI. In successful thrombolysis group 16 patient (53.3%) had anterior wall MI and 14 patients (46.7%) had non anterior MI. This difference was statistically not significant. Size of MI: Large MI (ST elevation in ≥7 leads) was seen in 15% of patients with failed thrombolysis and 13.3 % of patient with successful thrombolysis. Resolution of chest pain: The mean time for resolution of chest pain was higher in failed thrombolysis group (p<0.001). 85% patients with failed thrombolysis had chest pain for > 2hr after thrombolysis and it resolved in ≤ 2 hrs in 80% of patients with successful thrombolysis (p<0.001). Resolution of reciprocal ST depression: ST depression was seen in 12 and 18 patients with failed and successful thrombolysis at admission respectively. Among them 3(25%) and 15(83.3%) showed resolution of ST depression respectively which is statistically significant.

Discussion
In the present study we have studied the extent of failed thrombolysis in 50 patients admitted to ICCU, KIMS hospital, Hubli, who were eligible for streptokinase therapy. We have also studied the association of failed thrombolysis with the demographic, clinical and prognostic variables. The extent of failed thrombolysis varies from 15 to 50% in various studies. It depends on the criteria used for failed thrombolysis, drug used and inclusion and exclusion criterias used in a particular study. In present study failed thrombolysis was observed in 40% of patients using ≤50% maximum ST resolution at 90 min post thrombolysis with streptokinase as criteria. Richardson et al 7 15 showed significant association of diabetes with failed thrombolysis. Hypertension was seen in 20% of patients with failed and 16.7% of patients with successful thrombolysis which was not significant. Other studies also showed no significant association. Dyslipidemia was observed in 90% and 95% of patients with successful and failed thrombolysis with no significant association. Dobrzycki S et al (2003), 16 showed that persistent ST segment elevation patients had higher blood LDL and total cholesterol levels than patients with early ST resolution. There was no relation with blood levels of triglycerides or HDL cholesterol . Smoking was seen in higher percentage of patients with successful thrombolysis in present study but not significant. Similar observation was made by GISSI -2 10 and M Sezer et al. 12 Zahger D et al(1995), 17 showed that smoking was significantly associated with successful thrombolysis and lower mortality, which he attributed to incidence of acute MI in younger age and lesser atherosclerotic burden, more thrombus at the site in smokers. Killip class at presentation: GISSI -2 10 observed that higher the Killip class, more the extent of failed thrombolysis. This indicates that patient with cardiogenic shock are better treated with PTCA if available. In present study only a minor trend is observed. Heart rate and systolic blood pressure at presentation did not have an association with failed thrombolysis in present study. Variations according to site infarction: Anterior wall MI was seen in 70% and 53.3% of patients with failed and successful thrombolysis respectively. Inferior wall MI was seen in 30% and 46% of patients with failed and successful thrombolysis. There was a trend towards higher occurrence of failed thrombolysis in anterior wall MI and successful thrombolysis in inferior wall MI. Gabriel IB et al 11 and GISSI -2 10 showed this observation in significant proportions. Size of infarction: GISSI-2 10 showed larger infarctions have more successful thrombolysis and smaller infarction have more failed thrombolysis. Though such a difference was seen in present study it was statistically not significant. Time from onset of symptoms to thrombolysis: In present study mean time to thrombolysis was significantly high in failed group (5.85±2.47 hrs) when compared to successful group (4.55±2.4 hrs). GISSI-2 10 showed significantly higher proportion of successful thrombolysis in patients presenting within 3 hours. Shah et al 13 18 showed streptokinase had a failure rate 56.8% and history of diabetes mellitus, hypertension, anterior location of MI, longer door-to-needle time were highly predictive of thrombolysis failure using streptokinase. Strengths of present study -simple ECG parameters are used to assess the efficacy of thrombolysis, which can be used even by noncardiologists at a peripheral hospital. Limitations -Small number of patients studied. Angiography control not used and no interventional facilities available at our centre for failed thrombolysis.

Conclusion.
Long symptom to needle time is an important predictor of failed thrombolysis in acute myocardial infarction patients. Hence it is important to educate public about prompt recognition of symptoms and seeking medical help urgently. As it is also seen commonly in patients with old age, diabetes and dyslipidemia, such patients should be monitored and treated aggressively. Persistence of chest pain beyond 2 hours and non-resolution of reciprocal ST depression can serve as additional markers of failed thrombolysis. As failed thrombolysis can be associated with poor prognosis its recognition and appropriate further management is needed. artery patency and LV function to ECG changes after streptokinase treatment during acute MI.