According to the present statistics, end of this decade the non-communicable disease will cause 70% of deaths in developing countries. The use of thrombolytic strategies like Streptokinase has been reason for reduction in mortality and Reperfusion arrhythmias have been considered successful markers of reperfusion. The prevalence of reperfusion arrhythmias during and within 48 hours of intravenous streptokinase therapy, to assess the prognosis of myocardial infarction (MI) secondary to thrombolytic therapy, and find if the reperfusion arrhythmias are non-invasive markers of successful thrombolysis using the electrocardiogram. Methodology: 100 Patients admitted to NRI Institute of Medical Sciences, Sangivalsa, tertiary care, teaching hospital in South India, with features suggestive of acute myocardial infarction who have undergone thrombolytic therapy are selected for the study. These 100 patients were divided into 5 age groups as 35-45,46-55, 56-65,66-75 and 76-85years. Each age group was further divided into male and female groups. Adult patients of both sexes and different age groups after obtaining formal consent from the patients or relatives were included. Reperfusion arrhythmias during and within 48 hours of thrombolytic therapy using electrocardiography (ECG) were assessed. Results: Among all types of myocardial infractions (MI), Reperfusion Arrhythmias are more prevalent in anterior wall MI (43%) and less observed in inferoposterior wall MI (7%). The prevalence of the age and sex has been depicted. Maximum incidence of reperfusion arrhythmias was present in age group of 46-55 years i.e 28% followed by 66-75 i.e 26%,56-65-16%,35-45 and 76-85-15%. Among males and females, 57% of males and 43% of females showed maximum incidence. Results showed that there was no significant relationship between age and gender with reperfusion arrhythmias. There was a significant relationship observed between reperfusion arrhythmias and Diabetes (p=0.023). Incidence with hypertension (HTN) was 53%, and although hypertension was high in MI, the p-value was not significant between reperfusion arrhythmias and hypertension. Reperfusion arrhythmias incidence in risk factors such as alcoholics and smokers which was not significant, suggests that there was no statistical significance between these risk factors and arrhythmias. Observations drawn from results suggest that window period hospital presentation and types of myocardial infarction do not influence the occurrence of reperfusion arrhythmias (P=0.778) and there was a significant relation between reperfusion arrhythmias and survival of the effected patients of the study group (p=0.014).
Conclusion:
At beginning of the third millennium, the prevalence of non-communicable diseases is rising across the globe. According to the present statistics, end of this decade the non-communicable disease will cause 70% of deaths in developing countries. The major non-communicable diseases that are usually seen are cardiovascular diseases (ischemic heart disease-IHD and hypertension), diabetes, cancer, and chronic pulmonary disease.1-3 Burden of these conditions affects countries worldwide but with a growing trend in developing countries. Diabetes and hypertension, apart from other disabilities, can lead to IHD. Its is the most common, serious, chronic, life-threatening illness in the United States, where 13 million persons have IHD of which >6 million have angina pectoris, and >7 million have sustained myocardial infarction.4
These conditions are also a major cause of mortality and morbidity in the Asia-Pacific region and account for around half of the global burden i.e., around seven million deaths and 129 million disability-adjusted life years (DALYs) annually from 1990 to 2010 according to World Health Organization (WHO) records.5-9 The epidemiologic characteristics of acute myocardial infarction (AMI) have changed dramatically over the past three to four decades. Since 1987, the adjusted incidence rate of hospitalization for acute myocardial infarction or fatal coronary artery disease in the United States has declined by 4 to 5% per year.10,11 Nevertheless, approximately 5,50,000 first episodes and 2,00,000 recurrent episodes of acute myocardial infarction occur annually. Globally, ischemic heart disease has become the leading contributor to the burden of disease as assessed based on disability-adjusted life years.12
The use of thrombolytic strategies like Streptokinase has been prevalent for decades, and there was a significant reduction in mortality after the thrombolytic therapy. Reperfusion arrhythmias have been considered successful markers of reperfusion. Many studies regarding the consideration of reperfusion arrhythmias as a marker of reperfusion have been going on for decades. So, the main aim of this study is to see whether reperfusion arrhythmias can be considered prognostic indicators for thrombolysis or not.
Thus, this study aims to know the prevalence of reperfusion arrhythmias during and within 48 hours of intravenous streptokinase therapy, to assess the prognosis of myocardial infarction (MI) secondary to thrombolytic therapy, and find if the reperfusion arrhythmias are non-invasive markers of successful thrombolysis using the electrocardiogram.
100 Patients admitted to NRI Institute of Medical Sciences, Sangivalsa, tertiary care, teaching hospital in South India, with features suggestive of acute myocardial infarction who have undergone thrombolytic therapy are selected for the study. These 100 patients were divided into 5 age groups as 35-45,46-55, 56-65,66-75 and 76-85years. Each age group was further divided into male and female groups. Adult patients of both sexes and different age groups after obtaining formal consent from the patients or relatives were included. Reperfusion arrhythmias during and within 48 hours of thrombolytic therapy using electrocardiography (ECG) were assessed.
Inclusion Criteria
Exclusion Criteria
Patients with Congenital Heart Disease.
Statistical Analysis
Data were entered in MS Excel and analysed in SPSS V22. Descriptive statistics were done. The Chi-square test and ANOVA test were applied to find significance when needed. P ≤ 0.05 was considered statistically significant
Among all types of myocardial infractions (MI), Reperfusion Arrhythmias are more prevalent in anterior wall MI (43%) and less observed in inferoposterior wall MI (7%), (Table1). The prevalence of the age and sex has been depicted in Graph 1 and 2 respectively. Maximum incidence of reperfusion arrhythmias was present in age group of 46-55 years i.e 28% followed by 66-75 i.e 26%,56-65-16%,35-45 and 76-85-15%. Among males and females, 57% of males and 43% of females showed maximum incidence. Results from Tables 2 and 3 showed that there was no significant relationship between age and gender with reperfusion arrhythmias.
Diagnosis |
Reperfusion Arrhythmias |
|
Total |
|||
No |
Yes |
|
|
|||
Count |
% |
Count |
% |
Count |
% |
|
ALWMI |
8 |
13.6% |
6 |
14.6% |
14 |
14.0 % |
AN IF MI |
3 |
5.1% |
2 |
4.9% |
5 |
5.0 % |
AN INF MI |
4 |
6.8% |
3 |
7.3% |
7 |
7.0 % |
AWMI |
24 |
40.7% |
19 |
46.3% |
43 |
43.0 % |
IN PO MI |
5 |
8.5% |
1 |
2.4% |
6 |
6.0 % |
IN POST MI |
0 |
0.0% |
1 |
2.4% |
1 |
1.0 % |
IWMI |
15 |
25.4% |
9 |
22.0% |
24 |
24.0 % |
Total |
59 |
100.0% |
41 |
100.0% |
100 |
100.0 % |
Table 1: Relation of Reperfusion Arrhythmias with Type of Myocardial Infarction (MI) in Study Group |
||||||
Chi-square value = 3.24; df= 6; P=0.778 |
Age |
Reperfusion Arrhythmias |
|
Total |
|||
No |
Yes |
|
|
|||
Count |
% |
Count |
% |
Count |
% |
|
35-45 |
11 |
18.6% |
4 |
9.8% |
15 |
15.0 % |
46-55 |
16 |
27.1% |
12 |
29.3% |
28 |
28.0 % |
56-65 |
10 |
16.9% |
6 |
14.6% |
16 |
16.0 % |
66-75 |
14 |
23.7% |
12 |
29.3% |
26 |
26.0 % |
76-85 |
8 |
13.6% |
7 |
17.1% |
15 |
15.0 % |
Total |
59 |
100.0% |
41 |
100.0% |
100 |
100.0 % |
Table 2: Relation of Reperfusion Arrhythmias with Age Groups in Study Group |
||||||
Chi-square value = 1.88; df=4 ; P=0.758 |
Sex |
Reperfusion Arrhythmias |
|
Total |
|||
No |
Yes |
|
|
|||
Count |
% |
Count |
% |
Count |
% |
|
Female |
25 |
42.4% |
18 |
43.9% |
43 |
43.0 % |
Male |
34 |
57.6% |
23 |
56.1% |
57 |
57.0 % |
Total |
59 |
100.0% |
41 |
100.0% |
100 |
100.0 % |
Table 3: Relation of Reperfusion Arrhythmias with Sex Groups in Study Group |
||||||
Chi-square value = 0.023; df= 1; P=0.879 |
There was a significant relationship observed between reperfusion arrhythmias and Diabetes (p=0.023). Incidence with hypertension (HTN) was 53%, and although hypertension was high in MI, the p-value was not significant between reperfusion arrhythmias and hypertension. Reperfusion arrhythmias incidence in risk factors such as alcoholics and smokers which was not significant, suggests that there was no statistical significance between these risk factors and arrhythmias (Graph 3).
Observations drawn from results suggest that window period hospital presentation and types of myocardial infarction do not influence the occurrence of reperfusion arrhythmias (P=0.778) and there was a significant relation between reperfusion arrhythmias and survival of the effected patients of the study group (p=0.014) which is shown in Table 4.
Outcome |
Reperfusion Arrhythmias |
|
Total |
|||
No |
Yes |
|
|
|||
Count |
% |
Count |
% |
Count |
% |
|
Expired |
0 |
0.0% |
4 |
9.8% |
4 |
4.0 % |
Survived |
59 |
100.0% |
37 |
90.2% |
96 |
96.0 % |
Total |
59 |
100.0% |
41 |
100.0% |
100 |
100.0 % |
Table 4: Relation of Reperfusion Arrhythmias to Outcome in Study Group |
||||||
Chi-square value = 5.99; df= 1; P= 0.014 |
Arrhythmias and conduction disturbances are common during the early hours after an acute MI and a major cause of death in the pre-hospital phase. Their occurrence at the greatest frequency before or during thrombolysis indicates ongoing myocardial ischemia and reperfusion injury. STEMI is treated during the early window period of 8hrs with streptokinase or primary percutaneous intervention. Early thrombolysis is associated with a good prognosis in Acute MI. According to various studies and literature reperfusion arrhythmias during and within 48 hours of thrombolysis are associated with a good prognosis as well.
The term, reperfusion arrhythmias, was used in the first studies of thrombolytic therapy-guided revascularization in acute myocardial infarction. To confirm the presence of vessel patency and successful reperfusion of the myocardium following thrombolytic therapy, electrocardiographic data in addition to clinical and laboratory measures are used by the clinicians. These include normalization or more than 50% regression of ST elevation, T-wave inversion, and any other arrhythmia observed in electrocardiography. The most frequently observed arrhythmias that are defined as reperfusion arrhythmias are ventricular premature contractions, sustained or no sustained episodes of ventricular tachycardia, accelerated idioventricular rhythm, atrial fibrillation, and ventricular fibrillation. These arrhythmias are thought to be indicators of successful reperfusion.
According to Jurkovicova O, Cagan S13 reperfusion arrhythmias originate as a consequence of the complex cellular and humoral reactions accompanying the opening of the coronary artery. As the primary cause of their generation is considered the chemically defined substances that are produced and accumulated in the myocardium during reperfusion. The key role is ascribed to free oxygen radicals but of importance are also other substances such as calcium, thrombin, platelet-activating factor, inositol triphosphate, angiotensin II and others. These chemical mediators of reperfusion arrhythmias operate as modulators of cellular electrophysiology causing the complex changes at the level of ion channels. It is supposed that in the genesis of reperfusion arrhythmias unlike ischemic arrhythmias operate non-re-entrant mechanisms such as abnormal or enhanced automaticity and triggered activity due to depolarizations. As a typical reperfusion arrhythmia is considered an early (within 6 hours after the start of thrombolysis), frequent (> 30 episodes/hour), and repetitive (occurring during > 3 consecutive hours) Accelerated Idioventricular Rhythm (AIVR). AIVR with such characteristics has a high specificity and positive predictive accuracy but relatively low sensitivity as a predictor of reperfusion.
However, Gore et al.and14, Hacket et al15 do not find AIVR to be associated with successful reperfusion indicating ventricular rhythm may be a marker of early reperfusion and continuing arterial patency. In a previous study, the presence of accelerated idioventricular rhythm combined with normalization of ST segments was demonstrated to indicate successful reperfusion in patients treated with thrombolytics and there was no requirement for emergency coronary angiography and rescue percutaneous coronary intervention (PCI) in this group of patients. Among these, AIVR was the most sensitive and specific arrhythmia in cases of successful reperfusion.
Various types of arrhythmias were observed in the present study, AIVR is the most common type of reperfusion arrhythmias, 13% of patients developed this. This was a similar observation as seen in the studies done by Ersan Tatli et al16 (73.3%), and Terkelsen et al17 (42%) except the percentage was low in our study (13%). Chiladakis et al18 observed the presence of AIVR combined with normalization of ST segments, indicating successful reperfusion in patients treated with thrombolytics.
This study consists of 5 different groups of ST-segment elevation MI (STEMI) are anterior wall MI (AWMI)-43%, inferior wall MI (IWMI)-24%, anterolateral wall MI (ALWMI)-14%, anteroinferior wall MI (AN INF MI)-12%, inferoposterior wall MI (IN PO MI)-7% when compared to study done by Sarala. H. Tippannavar19 in which most of the patients (83%) had ST-segment elevation MI of which 34% had extensive anterior wall MI, 23% had inferior wall MI, 14% had anteroseptal wall MI, 6% had an inferior wall with Right ventricular (RV) extension, 3% had lateral and anterolateral wall MI each, and non-ST elevation MI patients were 17%.
This study was done to show the prevalence of reperfusion arrhythmias in STEMI during and within 48hrs of streptokinase therapy in different age and sex groups. Maximum incidence of acute STEMI was seen between 45-75 years 70% of them were in the 46-55years age group. Similarly, in a study done by MartinTC et al20, an incidence of 85% between 35-75 years of age was reported. Age incidence is probably more common because of lifestyle, economic status, multiple risk factors, and life expectancy.
In this study, 57 % of males and 43% of females showed arrhythmias similar to the study done by Martin TC et al20, where incidence was 72% in males and 28% in females, and by Kock HL et al21 where 72% were males and 24% were females. It is more common among males because of lifestyle and more risk factors like hypertension, smoking, diabetes mellitus, and alcohol.
It was observed in this study that 70% of the patients presented with chest pain, 15 % with shortness of breath (SOB), and 15% with both. It is compared to a study conducted by Mhatre MA et al.22 where the pattern and incidence of various symptoms of acute MI among which chest pain was the most common presenting symptom observed in 80% of patients and 15% of them had altogether epigastric pain and pain in left arm alone. Sweating was 2nd most common symptom (64%) followed by dyspnea (43%), Vomiting (28%), palpitation (11%), and giddiness /syncope (8%).
Risk factors like type 2 diabetes mellitus(DM) had an incidence of 38% in the present study as compared to 19% in Svensson AM et al23 study. It shows a higher incidence of type 2 diabetes mellitus in acute MI patients, indicating DM is a major risk factor. 53% had hypertension showing a higher prevalence of acute MI in disease groups which is in agreement with Kokubo Y et al24 study. This study has similar observations regarding DM and hypertension as seen in a study by Yavagal et al25 and in contrary to the study by Chatterjee et al.26 According to Ambrose and Barua et al27, cigarette smoke exposure is an important cause of cardiovascular morbidity and mortality. In this study 38% are associated with alcohol, however, several studies show that mild alcohol consumption has a protective role in acute coronary syndrome (ACS), whereas large amounts and binge intake are associated with acute MI. The role of alcohol as a risk factor is still controversial.
The following arrhythmias are regarded also as markers of reperfusion: frequent premature ventricular complexes (twofold increase in frequency within 90 minutes after the start of thrombolysis), a significant increase of episodes in nonsustained ventricular tachycardia, sinus bradycardia and probably also high-degree atrioventricular blocks, other probable arrhythmias include sinus tachycardia and ventricular fibrillation (VF). Thus, reperfusion arrhythmias are an important non-invasive marker of successful recanalization of the infarction-related coronary artery.
Sinus bradycardia (SB) was most associated with inferior wall myocardial infarction. In the present study, 3% had sinus bradycardia, out of which 2% were of inferior wall myocardial infarction (Graph 4). In all these patients, sinus bradycardia was transient, and majority of the patients had normal sinus rhythm (NSR) by the end of the first day. Similar observations were made by Swart G et al28, whereas in the study conducted by Michel Rotman et al29 10-30%, in Philip J Podrid30 study 16% to 25% of patients had sinus bradycardia, particularly of inferior wall MI and posterior wall MI. It was most often transient. Brady-arrhythmias and hypotension are common in proximal occlusion of the right coronary artery commonly leading to inferior myocardial infarction, because of reflexes arising from the ischemic right ventricle.
Sinus tachycardia was present only in 10%. This is mostly seen in AWMI-6% and IWMI-3%, as compared to Sarala. H. Tippannavar19 study. Where the incidence is 22%, it was so low in this study. There was no mortality in the present study group, which was contrary to Crimm A et al31, where the mortality incidence was 23.72%, in reference that sinus tachycardia is associated with adverse outcomes.
In the present study, there were no deaths in patients with SB and inferior wall MI, indicating a protective role of SB in inferior wall MI. Similar observations were made by Malla RR and Sayani A32. Occasionally they may progress to complete heart block so treatment with atropine and intravenous fluids and inotropes may be needed and in severe conditions may also need pacemaker implantation.
Overall, 15% of Ventricular arrhythmias are seen in present subjects, that is Ventricular fibrillation (VF) 1%, Ventricular Tachycardia (VT) 3%, Ventricular Premature Complexes (VPC) 11%, when compared to Henkel DM, Wltt BJ et al33 studies, where the incidence was low. In Ravi Kumar Navsk study34 Ventricular arrhythmias were present in 32% of them of which 24% had Ventricular Tachycardia (VT) and 28% had Ventricular Premature Beats (VPB). In Sarala. H. Tippannavar et al19 Ventricular arrhythmias were seen in 31 cases of which VPBs in 23 cases, VT in 6 cases, and VF in 2 cases. Mhatre MA et al22 show the overall incidence of ventricular arrhythmias being 33% of which VT was 24%, VPC was 8% and ventricular bigeminy was 1%, also overall incidence is more in anterior and lateral wall MI than inferior wall alone.
In this study, VPC’s are present in 11% population Which was of low incidence compared to Mohit J Shah et al35 study, in which VPCs were observed in 31% of the patients when they occurred alone. There is no mortality in VPC s in this study group, which indicates VPC has a good prognostic significance.
The incidence of VT in this study is 3%, 2% in AWMI, and 1% in AN IF MI contrary to a study done by Horvat D et al36 where VT was seen more in anterolateral MI than anteroseptal MI. In another study by Gibson et al37 exhibited the development of VT and VF in 3491 patients with STEMI after thrombolytic therapy. Mortality seen in patients with VT was 100% In the present study, whereas the study done by Metal GC and Al-Khatib S38 was 25.2% and 24% respectively. This discrepancy could be explained by larger infarcts and older age in the present study.
This study shows total mortality of 4% i.e. associated with VT/VF as compared with the study by Newby KH et al39 showed that sustained VT and VF occur in up to 20% of patients with AMI and have been associated with poor prognosis. It is a fact that primary VF, irrespective of timing, is an independent predictor of in-hospital mortality. In the study by Behar S et al40, the incidence of secondary VF complicating acute MI was 2.4% whereas a study done by Trappolini M et al41 shows 24.4% mortality, and a study by Simon T et al42 showed 25% mortality in females. This difference in mortality in this study may be explained by associated complications in present cases. In the current study, mortality is common in anterior wall MI and anteroinferior wall MI, as compared to Mohit J Shah et al35 mortality is high in anterior wall MI as compared to inferior wall MI.
Thus, RA is not an event of serious concern as they are usually well-tolerated and are amenable to treatment. They indicate effective reperfusion when present. Early streptokinase therapy has a favorable impact on mortality in MI and hence should be tried in all the Acute MI patients who do not have contraindications for streptokinase therapy.