Total Ischemic Time has Prognostic Implications on Short Term Outcome of Primary Percutaneous Coronary Intervention (pPCI)

Md. Golam Morshed , Muhammad Azmol Hossain , Housneara Begum , Md Shamsuzzaman , Kazi Mohammed Zafrul Haq , Md. Mozammel Haque , Md. Khurshid Alam & Poppy Bala

I. INTRODUCTION

Coronary artery disease (CAD) is the most common form of heart disease and single most important cause of premature death in most part of the world. By the year 2020 it will become the major cause of death in all the region of the world. Acute myocardial infarction (AMI) is one of the leading causes of death and disability. It generally occurs due to sudden occlusion of a coronary artery by formation of thrombus at the site of fissured or ruptured atherosclerotic plaque. The resultant thrombus that is formed interrupts blood flow and leads to an imbalance between oxygen supply and demand, if this imbalance is severe and persistent, it leads to myocardial necrosis. The major aspect of treatment of STEMI is reperfusion of the infarct related artery. Reperfusion therapy aims at restoration of antegrade flow in the occluded infarct related artery, which reduce infarct size and improves clinical outcome .

II. MATERIALS AND METHODS

This was a prospective observational study and was done in the department of cardiology in National Institute of Cardiovascular Diseases (NICVD), Dhaka, Bangladesh from August 2017 to July 2018. Patients presented with acute STEMI admitted in CCU in National Institute of Cardiovascular Diseases who full filled inclusion and exclusion criteria were my study population. Sampling was purposive.

Considering nonresponse, unavailability of some respondent, inflation in the desired sample size is planned. Targeted sample size for the study = 40 + 8= 48. Study subjects were divided into two groups on the basis of time delay to reperfusion: Group A (shorter ischemic time): Patients whose symptom onset to first balloon/ stent time was < 6 hours were included in this group and Group B (longer ischemic time): Patients whose symptom onset to first balloon/ stent time was 6-12 hours were included in this group.

Patients presented within 12 hours of onset of typical chest pain with ST segment elevation in ECG and diagnosed as a case of acute STEMI (ST segment elevation myocardial Infarction) were included in this study. Patients having LBBB (left bundle branch block). Patients with history of old myocardial infarction. Patients who received thrombolytic therapy. Patients with high bleeding risk. Patients with valvular heart disease. Patients with cardiomyopathies Patients with established renal failure (S. Creatinine > 2mg/dl.). Patients with stroke. Patients with malignancy were excluded in this study.

All variables were entered into the Statistical Package for Social Sciences, version 16 (SPSS Inc., Chicago, Illinois). Data was presented as frequency and percents for categorical variables and as mean with standard deviation for quantitative variables. Paired t-test was done for quantitative variables where applicable.

Univariate and multivariate regression analysis were done with variables may be related to adverse outcome with calculated risk ratios & odds ratios [OR] for independent variables with 95% confidence intervals [CI]. P value \<0.05 were considered as significant.

III. RESULTS AND DISCUSSIONS

This prospective observational study was conducted in the National Institute of Cardiovascular Diseases (NICVD), Dhaka during the period of August 2017 to July 2018. The main objective of this study was to assess the prognostic implication of total ischemic time on short term outcome of primary Percutaneous Coronary Intervention (PCI) among a case series of population presented with acute ST elevation myocardial infarction (STEMI).

A total of 48 patients with acute ST elevation myocardial infarction who were consented to PCI were included in this study. Patients were classified as shorter total ischemic time (group-A) in whom treatment delay was\<6 hours and longer total ischemic time (group-B) in whom treatment delay was 6-12 hours. Two patients died at the same day of the procedure and all other patients were followed up in hospital and for one month.

Table I: Comparison of risk factors between early treatment group and late treatment group (n=48) Group A: Total ischemic time \<6 hrs. Group B: Total ischemic time 6 – 12 hrs. Quantitative data expresses in mean ±SD and qualitative data expresses in no. &(%). s= Significant (p\<0.05), ns = Not significant (p>0.05) p value reached from Chi Square test.

The above table depicts the comparison of risk factors between early treatment group and late treatment group among the study population. Age, hypertension and diabetes were higher in patients with longer symptom onset to balloon time than in those with shorter symptom onset to balloon time and there were statistical significant association(p=0.03, p=0.03, p=0.04) respectively. Among the study population overall 41.7% were hypertensive, 45.8% were diabetic, 58.3% were dyslipidaemic and 72.9% were smoker.

Table II: Comparison of LVEF (%) between two groups before pPCI (n=48) Group A: Total ischemic time \<6 hrs. Group B: Total ischemic time 6 – 12 hrs. s = Significant (p\<0.05), p value reached from unpaired t-test.

The above table displays that among early presenters (group A) 8.7% had moderate LV dysfunction and 87% had mild LV dysfunction but among late presenters (group B) 28% had moderate LV dysfunction and 68% had mild LV dysfunction before pPCI.

Table III: Comparison of LVEF (%) between two groups after PPCI (n=48) Group A (n=23) Group A: Total ischemic time \<6 hrs. Group B: Total ischemic time 6 - 12 hrs. s = Significant (p\<0.05), p value reached from unpaired t-test.

The above table displays that after pPCI 91.3% patients had good LV function among those who are early presenter having total ischemic time \<6 hours and those who are late presenter having longer total ischemic time (6-12 hours) among them 88% had good LV function

Table IV: Adverse outcomes between group A (early treatment group) and group B (late treatment group) (n=48) at one month Group A: Total ischemic time \<6 hrs. Group B: Total ischemic time 6 – 12 hrs. S= Significant (p\<0.05), ns = Not significant (p>0.05) p value reached from Fisher's Exact test

The above table depicts that mortality in 1 month was 4.2%, heart failure was 6.2%, cardiogenic shock was 4.2%, major bleeding was 2.1% and minor bleeding was 14.6%. Most of the adverse outcomes occurred in late treatment group (6-12 hours from symptom onset to primary PCI) within one month. So it can be concluded that delay in symptom onset to balloon time (6-12 hrs) adversely affects the prognosis in patients with STEMI.

Table V: Univariate logistic regression of adverse short term outcome of pPCI

Dependent variable: Adverse in-hospital outcome; Independent variables: Advance age, male gender, hypertension, diabetes mellitus, smoking, anterior MI, multi vessel disease, lower LVEF (\<45%), pain to door time, door to balloon time and longer total ischemic time (6-12 hrs). s= Significant (p\<0.05), ns= Not significant (p>0.05)

Above table demonstrates the binary logistic regression analysis of odds ratio (OR) for characteristics of the subjects likely to develop adverse short time outcome of primary PCI. The variables revealed to be significantly associated with univariate analysis were entered into the model directly. In regression analysis advance age, hypertension, diabetes mellitus, anterior MI, multi vessel disease, pain to door time and longer total ischemic time (6-12hrs) were found to be the significant predictors for developing adverse short term outcome of primary PCI.

Table VI: Multivariate logistic regression of adverse short term outcome of pPCI

Dependent variable: Adverse in-hospital outcome; Independent variables: Advance age, male gender, hypertension, diabetes mellitus, smoking, anterior MI, multi vessel disease, lower LVEF (\<45%), pain to door time, door to balloon time and longer total ischemic time (6-12 hrs). s= Significant (p\<0.05), ns= Not significant (p>0.05)

Above table demonstrates the binary logistic regression analysis of odds ratio (OR) for characteristics of the subjects likely to develop adverse short time outcome of primary PCI. The variables revealed to be significantly associated with multivariate analysis were entered into the model directly. In regression analysis advance age, hypertension, diabetes mellitus, anterior MI, multi vessel disease, pain to door time and longer total ischemic time (6-12hrs) were found to be the independent predictors for developing adverse short term outcome of primary PCI with

ORs being 1.51, 2.44, 2.51, 1.38, 2.35, 1.66 and 2.67 respectively.

In multivariate analysis, we adjusted for potential confounders associated with the endpoints in univariate analysis. After correction for predictive baseline and procedural variables of the univariate analysis, longer total ischemic time was found as the most significant independent predictor (OR 2.67, p=0.02) of short term adverse outcome of primary PCI.

Reperfusion therapy (either mechanical or pharmacologic) is indicated for patients with chest pain with a duration of 12 hours or less in association with ST-segment elevation greater than 0.1 mV in two or more contiguous electrocardiographic leads or a new (or presumed new) left bundle-branch block. Early, effective and sustained reperfusion of the culprit artery is needed to salvage myocardium, maintain left ventricular function, and reduce mortality . Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for ST-segment elevated MI (STEMI) when it can be performed in a timely manner by experienced personnel . PCI for the treatment of STEMI was first reported by Hartzler . Primary PCI in the late eighties only comprised balloon angioplasty, resulted better survival of patients when compared with thrombolytic therapy; however the introduction of intracoronary stents showed much better clinical outcome as compared to balloon angioplasty only . If high-quality PCI is available, multiple randomized trials have shown enhanced survival compared to fibrinolysis with a lower rate of intracranial haemorrhage and recurrent myocardial infarction (MI) .

According to ACC/AHA guidelines for the treatment of STEMI patients, the time from medical contact to PCI (door-to-balloon time) should be 90 minutes and recommends a total ischemic time within 120 minutes . Compared to fibrinolysis, primary PCI restores more often angiographically normal flow, including optimal TIMI 3 flow and blush, and has additional importance in patients with a contraindication for fibrinolysis . Moreover, about a quarter of patients receiving fibrinolytic therapy has reocclusion of the infarct-related artery within 3 months after the myocardial infarction, with a recurrent infarction, which is very rare after primary PCI . Therefore, Primary percutaneous coronary intervention (PCI) is generally preferable to fibrinolytic therapy when time until treatment is short. Each 30-minute delay from symptom onset to Primary percutaneous coronary intervention (PCI) increases the relative risk for 1 year mortality by 8% .

However, effects of early reperfusion have been difficult to determine in STEMI patients undergoing primary PCI, with several published studies showing widely different treatment effects of early as compared to late reperfusion. While some studies have reported no effect on infarct size with shorter symptom-to-PCI timings

In our study, after correction for predictive baseline and procedural variables of the univariate analysis, longer total ischemic time was found as the most significant independent predictor (OR 2.67, p=0.02) of short term adverse outcome of primary PCI.

IV. LIMITATION OF THE STUDY

Although the result of this study supports the research question, there were some limitations of this study. These are, as the, sample size was small, it was difficult to generalize the findings to the reference population. Non randomized sampling done. Single centered study which didn't represent the status of the whole population. Short term observation. Angiography was evaluated by visual estimation, so there was chance of inter observer and intra observer variation of interpretation of the TIMI flow and MBG.

V. CONCLUSION

The results of this study strongly support the prognostic implication of total ischemic time in patients with STEMI undergoing primary PCI. Therefore, all efforts should be made to shorten total ischemic time, including reduction in patient related delays, to improve clinical outcome of STEMI patients.

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