Emergency. 2017; 5 (1); e73 OR I G I N A L RE S E A RC H The Relationship of ST Segment Changes in Lead aVR with Outcomes after Myocardial Infarction; a Cross Sectional Study Mohammad Reza Beyranvand1, Mohammad Assadpour Piranfar1, Mohammadreza Mobini2, Mehdi Pishgahi2∗ 1. Department of Cardiology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2. Department of Cardiology, Shohadaye Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Received: May 2017; Accepted: June 2017; Published online: 30 June 2017 Abstract: Introduction: Among the 12 leads studied in electrocardiography (ECG), lead aVR can be considered as the most forgotten part of it since no attention is paid to it as the mirror image of other leads. Therefore, the present study has been designed with the aim of evaluating the prevalence of ST segment changes in lead aVR and its relation- ship with the outcome of these patients. Methods: In this retrospective cross sectional study medical profiles of patients who had presented to emergency department with the final diagnosis of myocardial infarction (MI) in a 4-year period were evaluated regarding changes of ST segment in lead aVR and its relationship with in-hospital mortality, the number of vessels involved, infarct location and cardiac ejection fraction. Results: 288 patients with the mean age of 59.00 ± 13.14 (18 – 91) were evaluated (79.2% male). 168 (58.3%) patients had the men- tioned changes (79.2% male). There was no significant relationship between presence of ST changes in lead aVR with infarct location (p = 0.976), number of vessels involved (p = 0.269) and ejection fraction on admission (p = 0.801). However, ST elevation ≥ 1 mv in lead aVR had a significant relationship with mortality (Odds = 7.72, 95% CI: 3.07 – 19.42, p < 0.001). Sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios of ST elevation ≥ 1 for prediction of in-hospital mortality were 41.66 (95% CI: 22.79 – 63.05), 91.53 (95% CI: 87.29 – 94.50), 31.25 (95% CI: 16.74 – 50.13), 94.44 (95% CI: 90.65 – 96.81), 0.45 (95% CI: 0.25 – 0.79), and 0.05 (95% CI: 0.03 – 0.09), respectively. Conclusion: Based on the results of the present study, the prevalence of ST segment changes in lead aVR was estimated to be 58.3%. There was no significant relationship between these changes and the number of vessels involved in angiography, infarct location and cardiac ejection fraction. However, presence of ST elevation ≥ 1 in lead aVR was associated with 8 times increase in in-hospital mortality risk. Keywords: Myocardial infarction; electrocardiography; patient outcome assessment; st elevation myocardial infarction © Copyright (2017) Shahid Beheshti University of Medical Sciences Cite this article as: Beyranvand M, Assadpour Piranfar M, Mobini M, Pishgahi M. The Relationship of ST Segment Changes in Lead aVR with Outcomes after Myocardial Infarction; a Cross Sectional Study. Emergency. 2017; 5(1): e73. 1. Introduction C hest pain caused by myocardial infarction (MI) is among the most common causes of patients visiting emergency departments (EDs). There has been a pre- diction of 80% increase in cases affected with problems re- lated to coronary arteries in developing countries such as ∗Corresponding Author: Mehdi Pishgahi; Cardiology Department, Shoha- daye Tajrish Hospital, Shahrdari Avenue, Tajrish Square, Tehran, Iran. Email: mp_cr1@yahoo.com Tel/Fax: 00989123387486 India, Latin America Region, Middle East, and African Sa- hara by 2020 (1, 2). Predicting the outcome of these pa- tients can be helpful in more proper triage, giving informa- tion to their relatives, and more accurate care for the more severe cases. The final outcome of these patients depends on various factors such as age, size and place of the infarc- tion, residual left ventricular function, presence of under- lying illnesses, and delay in reperfusion of affected arteries (3-6). Numerous studies have been done regarding the re- lationship between electrocardiogram (ECG) evidence with angiography findings and final outcome of these patients and This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com M. Beyranvand et al. 2 among them, ST segment changes in lead aVR has been as- sociated with poor outcome of patients with MI during their hospitalization period (7-9). In a study by Kukla et al. pa- tients who had ST-elevation in lead aVR, faced in hospital death 1.5 times those with ST-depression and about 30 times those without changes in ST segment (10). In addition, find- ings of Senaratne et al. revealed that mortality rate was 16 times higher in patients who had MI with ST depression in lead aVR (11). They expressed that although ST segment de- pression in lead aVR is difficult to diagnose, it can be good evidence of ischemia or injury to apex and infrolateral re- gions of the heart. Presence of ST segment depression is indicative of a larger area on the cardiac muscle being in- volved and somehow shows the need for more invasive in- terventions (12, 13). Additionally, ST elevation in lead aVR has been associated with increased probability of recurrent infarction, developing cardiac failure and increased need for bypass surgery of coronary arteries (12). A study by Kosuge et al., indicated 78% sensitivity and 86% specificity of more than 0.05 mV ST segment elevation in aVR lead for predicting involvement of all 3 cardiac vessels (14). Until now, no sim- ilar studies have been carried out on Iranian patients in this field; therefore, the present study has been designed with the aim of evaluating the relationship of ST segment elevation in lead aVR with the final outcome of the patients with MI pre- senting to ED. 2. Methods 2.1. Study design In this retrospective cross sectional study medical profiles of patients who were hospitalized in Taleghani Hospital, Tehran, Iran, during the time between 2012 and 2015 with the final diagnosis of MI were evaluated with the aim of assessing the prevalence of ST segment changes in lead aVR and its re- lationship with the outcome of studied patients. The study was approved by the ethics committee of Shahid Beheshti University of Medical Sciences. Researchers adhered to the principles of Helsinki declaration and keeping patients’ data confidential. 2.2. Participants Patients who had been hospitalized with the final diagnosis of MI in the mentioned period were evaluated without any age or sex limitations. Inclusion criteria consisted of time in- terval of less than 24 hours between chest pain and present- ing to ED, confirmation of MI based on clinical findings and raise in cardiac enzymes (CPKMB or troponin) in the initial 48 hours of admission. Patients with a history of coronary artery bypass grafting (CABG), history of heart blocks includ- ing left bundle branch block (LBBB) and right bundle branch block (RBBB), and those with a pace maker as well as cases where the information was not completely available were ex- cluded from the study. 2.3. Data gathering Data gathering was done using a pre-designed checklist by referring to patients’ medical profile. A senior cardiology res- ident was in charge of gathering patients’ data. Studied vari- ables included demographic data (age and sex), vital signs of the patient on admission to ED, medical history, drug his- tory, left ventricle ejection fraction based on echocardiogra- phy findings, ECG findings regarding changes of ST segment in lead aVR, angiography findings regarding number and lo- cation of coronary artery involvement and finally, mortality of the patients. Locating the infarct zone was done based on ECG findings and Echocardiography confirmation. 2.4. Statistical Analysis The sample size required for performing the study was esti- mated as 288 cases by considering the probability of changes being present in lead aVR to be 25%, type 1 error of 5%, 80% power, and d = 10%. SPSS21 software was used for statisti- cal analysis. To report variables, descriptive statistics such as mean ± standard deviation or frequency and percentage were used in tables and a chart. To compare qualitative vari- ables chi square or Fisher’s exact tests and for quantitative cases, t-test was applied. Additionally, sensitivity, specificity, positive and negative predictive values and positive and neg- ative likelihood ratio as well as area under the receiver oper- ating characteristic (ROC) curve of ST elevation ≥ 1 in lead aVR were calculated and reported with 95% confidence in- terval using Med Calc software. P < 0.05 was considered as significance level. 3. Results 3.1. Baseline characteristics 288 patients with the mean age of 59.00 ± 13.14 (18 – 91) were evaluated (79.2% male). Mean duration of hospitaliza- tion was 6.11 ± 4.82 (1 – 45) days. 247 (85.8%) of the MI cases were ST elevation MI (STMI) and 41 (14.2%) cases had non STMI. Table and figure 1 show the baseline characteris- tics of the studied patients. More than half of the patients were over 60 years old (50.3%). Only, 11 (3.8%) patients had unstable hemodynamics on presentation to ED and all but 10 (3.5%) patients had degrees of decrease in cardiac ejec- tion fraction on admission to ED. Based on the results of an- giography, 93 (32.3%) cases had three vessel involvement, 85 (29.5%) had two vessel, 63 (21.9%) had single vessel involve- ment and in 4 cases angiography was normal. Table 2 depicts the location of vascular lesion based on angiography results. 168 (58.3%) patients had changes of ST segment in lead aVR (79.2% male). Findings regarding changes in ST segment el- This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com 3 Emergency. 2017; 5 (1); e73 Table 1: Baseline characteristics of the studied patients Variable N (%) Sex Male 228 (79.2) Female 60 (20.8) Age (year) 15 - 30 6 (2.1) 30 - 45 26 (9.0) 45 - 60 111 (38.5) ≥ 60 145 (50.3) Hemodynamic Stable 275 (95.5) unstable 11 (3.8) Medical history Smoking 129 (44.8) Diabetes mellitus 78 (27.1) Hypertension 119 (41.3) Hyperlipidemia 85 (29.5) Prior MI 23 (0.8) Prior CVA 21 (7.3) Drug History Calcium channel blockers 10 (3.5) β blockers 252 (78.5) Nitrates 158 (54.9) Aspirin 253 (87.8) Clopidogrel 230 (79.9) Statins 255 (88.5) ACEI/ARB 240 (83.3) LVEF (%) ≥ 55 10 (3.5) 45 – 55 138 (47.9) 35 – 45 78 (25.7) < 35 38 (13.2) MI: myocardial infarction; CVA: cardiovascular accident; LVEF: left ventricular ejection fraction; ACEI/ARB: angiotensin -converting enzyme inhibitor/angiotensin-receptor blocker. evation in lead aVR are summarized in table 3. There was no relationship between presence of these changes with age (p = 0.260), sex (p = 0.977) and type of MI (p = 0.247). 3.2. Relationship of ST segment changes with outcome There was no significant relationship between presence of ST changes in lead aVR with infarct location (p = 0.976), number of vessels involved (p = 0.269) and cardiac ejection fraction on admission (p = 0.801). Out of the 32 (11.1%) patients who finally died, 25 (78.1%) had ST changes in lead aVR (Odds = 2.72, 95% CI: 1.13 – 6.52, p < 0.020). 3.3. Relationship of ST elevation ≥ 1 mv with outcome There was no relationship between presence of ST elevation ≥ 1 mv in lead aVR with infarct location (p = 0.466), number of vessels involved (p = 0.206) and cardiac ejection fraction Table 2: Location of vascular lesion based on angiographic findings Arteries N (%) Left main 1 (0.3) Left anterior descending Proximal 41 (14.2) Medial 80 (27.8) Distal 5 (1.7) Left circumflex Proximal 4 (1.4) Medial 11 (3.8) Distal 2 (0.7) Right coronary Proximal 30 (10.4) Medial 33 (11.5) Distal 10 (3.5) Others 25 (8.7) Table 3: ST segment changes in lead aVR of the studied patients ST changes N (%) Normal Isoelectric 116 (40.3) Elevation 0.5 - 1 79 (27.4) ≥ 1 24 (8.3) Depression 0.5 - 1 53 (18.4) ≥ 1 12 (4.1) on admission (p = 0.369). However, it had a significant re- lationship with mortality (Odds = 7.72, 95% CI: 3.07 – 19.42, p < 0.001). Sensitivity, specificity, positive and negative pre- dictive values and positive and negative likelihood ratios of ST elevation ≥ 1 mv in lead aVR for prediction of in-hospital mortality were 41.66 (95% CI: 22.79 – 63.05), 91.53 (95% CI: 87.29 – 94.50), 31.25 (95% CI: 16.74 – 50.13), 94.44 (95% CI: 90.65 – 96.81), 0.45 (95% CI: 0.25 – 0.79), and 0.05 (95% CI: 0.03 – 0.09), respectively. In addition, based on area under the ROC curve its accuracy was 0.66 (95% CI: 0.53 – 0.76) (fig- Figure 1: Infarct Location based on electrocardiographic findings. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com M. Beyranvand et al. 4 Figure 2: The area under the ROC curve of ST segment elevation ≥ 1 millivolt in predicting the mortality of patients with myocardial infarction. ure 2). 3.4. Relationship of ST depression ≥ 1 mv with outcome There was no significant relationship between ST depression ≥ 1 in lead aVR with infarct location (p = 0.160), number of vessels involved (p = 0.521), cardiac ejection fraction on ad- mission (p = 0.309) and mortality (p = 0.546). 4. Discussion Based on the results of the present study, the prevalence of ST segment changes in lead aVR was estimated to be 58.3%. There was no significant relationship between these changes and the number of vessels involved in angiography, infarct location and cardiac ejection fraction. However, presence of ST elevation ≥ 1 in lead aVR was associated with 8 times increase in in-hospital mortality risk. ECG, as a cheap and non-invasive method, has been used for more than 70 years around the world to diagnose cardiac tissue ischemia and MI. Among the 12 leads studied in ECG, lead aVR can be con- sidered as the most forgotten part of it since no attention is paid to it as the mirror image of other leads. In the last few decades, this lead is regaining its place as an important part of ECG among cardiologists. ST segment changes can be con- sidered as the most important ECG finding in diagnosis and evaluation of MIs. Lead aVR is a good reference regarding things that occur in the upper and right side of the heart (15). The findings of this lead are usually covered by the informa- tion from the left leads of the heart such as aVL, II, V5, and V6; that is why it has been forgotten. Researchers Yamaji et al. in 2001 had believed that ST segment elevation changes are good indicators of ischemia in the basal parts of the interven- tricular septum of the heart (16). On the other hand, Gorgels et al. in Netherlands could link the elevation of ST segment in aVR with obstruction of the proximal region of the left an- terior descending (LAD) artery and involvement of the first septal branch of this artery (15). Involvement of the distal parts of LAD is usually accompanied by ST segment depres- sion in aVR. Wong et al. in 2012 went further and suggested a U shape relationship between 30-day mortality of those with anterior MI and ST level in aVR (17). So that more than 0.5 mv ST segment depression in aVR was associated with higher mortality rate during the 30 days after occurrence of anterior MI. The last chest lead (V6) is placed on the axilla midline and a lead V7 in the posterior axillary line can show wide ischemia of the cardiac tip more clearly. This finding is indicative of the importance of the mirror image in aVR, which is more reflec- tive of ischemia in the apex of the heart and shows the mir- ror image of V7 more than any other lead. This means that deeper depression in aVR in ST is a sign of higher ST eleva- tion not only in V5 and V6 leads but also in V7 (17). Using ST segment, T wave and Q wave in lead aVR to evaluate the cur- rent or past situation of the patients such as previous or cur- rent MI has been suggested in various studies (18). Although Wong believes that ST segment changes in lead aVR are not significantly related to mortality of MI patients, in 2012 Kukla et al. announced that among 320 patients with inferior MI who had ST segment changes in various leads of ECG, these changes in lead aVR had occurred in half the patients and had a significant relationship with poor prognosis for their problem (10, 17). In the present study, a significant statistical relationship was found between ST segment changes in lead aVR and mortality of the patients. The higher the elevation, the higher the prevalence of mortality. ST segment depres- sion and isoelectric level of the segment, respectively, were associated with lower levels of mortality. Some studies have expressed the higher importance of ST segment elevation in aVR compared with this segment’s depression (12). Mean- while, Kukla et al. in their study on 320 individuals observed that patients with inferior wall MI, in case of ST elevation in aVR had a mortality rate 1.5 times those who had ST de- pression and 30 times those with isoelectric ST in aVR (10). While, Senaratne in 2003 showed that ST segment depres- sion in aVR was associated with 16 times more patient mor- tality compared to other cases (11). Regarding the anatomy of coronary arteries’ involvement and its relationship with changes in lead aVR, no significant relationship was found in our study; however, ST segment elevation in aVR was ac- companied with higher involvement of all 3 coronary arter- ies. On the other hand, although not statistically significant, proximal obstruction of LAD and medial obstruction of the left circumflex artery was accompanied by higher mortality This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com 5 Emergency. 2017; 5 (1); e73 in patients. Mortality rate in the present study was 11.1%, which is higher than the mean mortality rate reported dur- ing hospital stay in a meta-analysis done by Sorita et al in 2014 (7%) (19). This meta-analysis was carried out on 48 re- search studies related to the topic and more than 1.5 million patients, and reported mortality of MI patients to be 12% dur- ing the 30 days after occurrence of MI. Although this study was done on 288 MI patients and the sample size and power of the study were acceptable, its only statistically significant finding was the relationship between ST segment elevation in lead aVR and in-hospital mortality, which is of course highly important, and ST changes in lead aVR did not significantly change with LVEF changes and coronary artery involvement and its location. It seems that performing prospective cohort studies by considering all of the identified risk factors in pre- diction of MI patients’ outcome can give a more accurate pic- ture of the role of lead aVR findings in prediction of outcome and estimation of location or extent of the necrosis occurring following ischemia. 5. Limitation This study was done retrospectively by evaluating patients’ medical profiles and therefore, had the natural limitations as- sociated with these studies such as missing information and not being sure of the accuracy of the reports. Other known risk factors of patient outcome were not evaluated in this study, thus, multivariate analysis for identifying independent factors could not be performed. 6. Conclusion Based on the results of the present study, the prevalence of ST segment changes in lead aVR was estimated to be 58.3%. There was no significant relationship between these changes and the number of vessels involved in angiography, infarct location and cardiac ejection fraction. However, presence of ST elevation ≥ 1 mv in lead aVR was associated with 8 times increase in in-hospital mortality risk. 7. Appendix 7.1. Acknowledgements We appreciate the cooperation of all the staff of archive unit of medical records in Taleghani Hospital, Tehran, Iran. 7.2. Author contribution All authors passed four criteria for authorship contribution based on recommendations of the International Committee of Medical Journal Editors. 7.3. Funding/Support None. 7.4. Conflict of interest None. References 1. Reddy KS. Cardiovascular disease in non-Western coun- tries. N Engl J Med. 2004;350(24):2438-40. 2. Okrainec K, Banerjee DK, Eisenberg MJ. Coronary artery disease in the developing world. Am Heart J. 2004;148(1):7-15. 3. Antman EM, Cohen M, Bernink PJ, McCabe CH, Ho- racek T, Papuchis G, et al. The TIMI risk score for un- stable angina/nonâĂŞST elevation MI: a method for prognostication and therapeutic decision making. Jama. 2000;284(7):835-42. 4. James SK, Lindahl B, Siegbahn A, Stridsberg M, Venge P, Armstrong P, et al. N-terminal pro–brain natriuretic pep- tide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in pa- tients with unstable coronary artery disease. Circulation. 2003;108(3):275-81. 5. de Lemos JA, Morrow DA, Bentley JH, Omland T, Saba- tine MS, McCabe CH, et al. The prognostic value of B-type natriuretic peptide in patients with acute coro- nary syndromes. New England Journal of Medicine. 2001;345(14):1014-21. 6. Haaf P, Reichlin T, Corson N, Twerenbold R, Reiter M, Steuer S, et al. B-type natriuretic peptide in the early di- agnosis and risk stratification of acute chest pain. The American journal of medicine. 2011;124(5):444-52. 7. Alherbish A, Westerhout CM, Fu Y, White HD, Granger CB, Wagner G, et al. The forgotten lead: Does aVR ST-deviation add insight into the outcomes of ST- elevation myocardial infarction patients? Am Heart J. 2013;166(2):333-9. 8. Vikas Mishra M, Ramesh Thakur D, Jha MJ, Amit Goel M, Ashutosh Kumar M, Chandra Mohan Varma D, et al. Pre- diction of St deviations in lead avr as a noninvasive tool to predict the infarct-related coronary artery in patients with acute inferior-wall Myocardial infarction (the PreSt- riMi Study). 9. Ji ZG. TCTAP A-006 Clinical Significance of ST-Segment Changes in Lead aVR for Patients with Acute Coronary Syndrome. J Am Coll Cardiol. 2015;65(17):S3. 10. Kukla P, Bryniarski L, Dudek D, Krolikowski T, Kawecka K. Prognostic significance of ST segment changes in lead aVR in patients with acute inferior myocardial infarc- tion with ST segment elevation. Kardiologia Polska (Pol- ish Heart Journal). 2012;70(2):111-8. 11. Senaratne MP, Weerasinghe C, Smith G, Mooney D. Clin- ical utility of ST-segment depression in lead AVR in acute myocardial infarction. J Electrocardiol. 2003;36(1):11-6. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com M. Beyranvand et al. 6 12. Barrabes JA, Figueras J, Moure C, Cortadellas J, Soler- Soler J. Prognostic value of lead aVR in patients with a first non-ST-segment elevation acute myocardial infarc- tion. Circulation. 2003;108(7):814-9. 13. Mahmoud KS, Al Rahman TMA, Taha H, Mostafa S. Sig- nificance of ST-segment deviation in lead aVR for predic- tion of culprit artery and infarct size in acute inferior wall ST-elevation myocardial infarction. The Egyptian Heart Journal. 2015;67(2):145-9. 14. Kosuge M, Kimura K, Ishikawa T, Ebina T, Hibi K, Toda N, et al. ST-segment depression in lead aVR: a useful predictor of impaired myocardial reperfusion in patients with inferior acute myocardial infarction. CHEST Jour- nal. 2005;128(2):780-6. 15. Gorgels AP, Engelen D, Wellens HJ. Lead aVR, a mostly ig- nored but very valuable lead in clinical electrocardiogra- phy. Journal of the American College of Cardiology; 2001. 16. Yamaji H, Iwasaki K, Kusachi S, Murakami T, Hirami R, Hamamoto H, et al. Prediction of acute left main coro- nary artery obstruction by 12-lead electrocardiography: ST segment elevation in lead aVR with less ST segment elevation in lead V1. J Am Coll Cardiol. 2001;38(5):1348- 54. 17. Wong C-K, Gao W, Stewart RA, French JK, Aylward PE, White HD. The prognostic meaning of the full spectrum of aVR ST-segment changes in acute myocardial infarc- tion. Eur Heart J. 2012;33(3):384-92. 18. Tamura A. Significance of lead aVR in acute coronary syn- drome. World J Cardiol. 2014;6(7):630. 19. Sorita A, Ahmed A, Starr SR, Thompson KM, Reed DA, Prokop L, et al. Off-hour presentation and outcomes in patients with acute myocardial infarction: systematic re- view and meta-analysis. BMJ. 2014;348:f7393. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com Introduction Methods Results Discussion Limitation Conclusion Appendix References