precordial total R wave

    A Simple Independent Prognostic Electrocardiography Parameter in First Acute Anterior Myocardial Infarction; Precordial Total Q wave/ Precordial Total R wave Mert ˙Ilker Hayıro˘glu MD, Ahmet Okan Uzun, Muhammed Keskin, Ed¨ ibe Bet¨ul B¨orkl¨u, Ahmet ˙Ilker Tekkes¸in, Ceyhan T¨urkkan, Omer Kozan PII: DOI: Reference:

S0022-0736(17)30339-4 doi: 10.1016/j.jelectrocard.2017.09.008 YJELC 52507

To appear in:

Journal of Electrocardiology

˙ Please cite this article as: Hayıro˘glu Mert Ilker, Uzun Ahmet Okan, Keskin Muhammed, ˙ ¨ B¨orkl¨ u Edibe Bet¨ ul, Tekke¸sin Ahmet Ilker, T¨ urkkan Ceyhan, Kozan Omer, A Simple Independent Prognostic Electrocardiography Parameter in First Acute Anterior Myocardial Infarction; Precordial Total Q wave/ Precordial Total R wave, Journal of Electrocardiology (2017), doi: 10.1016/j.jelectrocard.2017.09.008

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ACCEPTED MANUSCRIPT A Simple Independent Prognostic Electrocardiography Parameter in First Acute Anterior Myocardial Infarction; Precordial Total Q wave/ Precordial

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Total R wave

Mert İlker Hayıroğlu1, Ahmet Okan Uzun2, Muhammed Keskin1, Edibe Betül Börklü3, Ahmet

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İlker Tekkeşin3, Ceyhan Türkkan3, Ömer Kozan1 1

Department of Cardiology, Haydarpasa Sultan Abdulhamid Han Training and Research

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Hospital, Istanbul, Turkey

Department of Cardiology, Hatay Dortyol State Hospital, Hatay, Turkey

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Department of Cardiology, Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Training

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and Research Hospital, Istanbul, Turkey

Running Head: Electrocardiography Parameter in Anterior Myocardial Infarction

infarction

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Keywords: Electrocardiography; in-hospital mortality, Q wave, R wave, myocardial

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Word Count: 2901

Corresponding Author: Mert İlker Hayıroğlu, MD. Department of Cardiology, Haydarpasa Sultan Abdulhamid Han Training and Research Hospital, 34668 Kadikoy-Istanbul Turkey E-mail: [email protected] Phone: +90 535 7154808

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ACCEPTED MANUSCRIPT Abstract

Background

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Acute transmural ischemia due to left anterior descending artery (LAD) occlusion changes precordial R and Q wave amplitudes owing to depressed intramyocardial activation. The prognostic effect of R and Q wave amplitudes in acute myocardial infarction (MI) was previously tested. We investigated the prognostic value of precordial total Q wave

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amplitude/precordial total R wave amplitude ratio (Q/R) in patients with first acute anterior

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MI treated with primary percutaneous coronary intervention. (PPCI)

Methods

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In this prospective analysis, we evaluated the in-hospital prognostic impact of Q/R on 354 patients with first acute anterior MI. Patients were stratified by tertiles of admission Q/R,

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clinical outcomes were compared between those groups.

Results

In-hospital univariate analysis revealed notably higher rates of in-hospital death for patients in tertile 3, as compared to patients in tertile 1 (OR 9.7, 95% CI 2.8 – 33.5, p<0.001). After

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adjustment for confounding baseline variables, Q/R in tertile 3 was associated with 6.9-fold hazard of in-hospital death (OR: 6.9, 95% CI 2.1 – 41.1, p<0.001). Spearman correlation

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analysis revealed correlation between Q/R and left ventricle ejection fraction.

Conclusion

Q/R in admission ECG in patients with first acute anterior MI treated with PPCI provide an independent prognostic marker of in-hospital outcomes. Our data suggests Q/R to be a simple, feasible and clinically applicable tool for rapid risk stratification in patients with first acute anterior MI.

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ACCEPTED MANUSCRIPT Introduction

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Electrocardiography (ECG) is the most useful clinical tool for the characterization of myocardial infarction (MI). After detection of ST segment elevation MI, total occlusion of left anterior descending artery (LAD) is more jeopardous due to its extensive perfusing territory.

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Thus admission parameters increased in value in patients with acute anterior MI to predict inhospital and long-term outcomes. Although serum level of laboratory markers, transthoracic

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echocardiography and physical capacity are functional in predicting survival in acute anterior

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MI, they can be time consuming. (1) Since ECG is first diagnostic method and easily accessible, investigations regarding its components’ prognostic value in MI have been

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continued. Several admission ECG parameters have been postulated to adjust prognosis in patients with acute MI. R wave amplitude, Q wave appearance at admission ECG and prominent Q wave in lead -aVR have been newly introduced into literature as a prognostic parameter in acute MI. (2-4) Q waves appear on 12-lead ECG during acute MI and symbolize

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loss of electrical activity. Q waves are unrelated to symptom duration and may appear early in

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MI. (5) Despite symptom independence, Q wave is strongly connected with myocardial contractile function. Therefore it was considered as a representative indicator for myocardial damage. (6) Apart from Q wave, R wave amplitude varies from increase to decrease as a result of transmural ischemia duration. (7) R wave amplitude was also proved to be a prognostic indicator in patients with ST segment elevated MI. (2) Since admission precordial Q and R waves have a prognostic impact on survival, we attempted to put forward a new prognostic ECG parameter for the first time in this prospective study. The aim of this study was to assess the prognostic value of precordial total Q wave amplitude to precordial total R wave amplitude ratio (Q/R) in patients with first acute anterior MI treated with primary percutaneous coronary intervention (PPCI).

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ACCEPTED MANUSCRIPT Material and methods

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Patient and study design

Between January 2015 and February 2016, 402 consecutive patients of all ages with acute

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anterior MI of <12 hour symptom duration, who underwent PPCI, were prospectively enrolled in the study. Patients were admitted to emergency department of a tertiary heart center.

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Patients were included if they had persistent ischemic chest pain with ST segment elevation.

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STEMI was diagnosed according to guidelines which was defined as elevation in two contiguous leads and was ≥0.25 mV in men below the age of 40 years, ≥0.2 mV in men over

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the age of 40 years, or ≥0.15 mV in women in leads V2 –V3 and/or ≥0.1 mV in other leads. (8) Excluded patients were those undergoing urgent angiography for ST segment elevation MI other than acute anterior MI, non-ST segment elevation MI or unstable angina pectoris. Patients with confounding features on their ECG such as bundle branch block, paced rhythm

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and poor quality; those who underwent urgent coronary artery bypass surgery (CABG) in their

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hospitalization period or who received thrombolysis before PPCI were also excluded in order to minimize bias. Among 402 patients, those with previous MI or PCI (n=13), those with bundle branch block (n=28), those underwent urgent coronary artery bypass surgery (n=5) and those with paced rhythm or poor quality ECG (n=2) were excluded. Therefore 354 patients without known coronary artery disease, previous MI or PCI admitted to emergency department with acute anterior MI treated with PPCI were enrolled in the study. Our cardiology team informed patients about the study and their informed consents were obtained. The Local Ethical Committee of our hospital approved the study protocol. Baseline demographic characteristics and related clinical information were obtained from each patient at the time of their emergency department admission. Before the PPCI,

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ACCEPTED MANUSCRIPT transthoracic echocardiography (TTE) was performed using a Vivid 7 system (GE Vingmed Ultrasound AS, Horten, Norway) on study patients by an expert on cardiovascular imaging.

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Left ventricular ejection fraction (LVEF) was calculated by using Simpson method. (9) The pulmonary arterial peak systolic pressure was calculated using the simplified Bernoulli equation (10)

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Blood values obtained from venous blood samples at hospital admission were recorded. White blood cell (WBC), hemoglobin level, and neutrophil counts were measured as part of

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the automated complete blood count using a Coulter LH 780 Hematology Analyzer (Beckman

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Coulter Ireland, Inc, Galway, Ireland). Biochemical measurements were performed using Siemens Healthcare Diagnostic Products kits and calibrators (Marburg, Germany). Creatinine

8000; Abbott Inc).

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kinase isoenzyme–MB levels were measured using an immune-inhibition method (Architect C

A standard 12-lead ECG (Schiller, Cardiovit AT-10 plus) (filter 150Hz, 25 mm/s, 10 mm/mV) was obtained from all patients prior to PPCI. ECGs were scanned at 300 DPI and

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images were amplified 10x. Precordial (V1-V6) R and Q waves’ amplitudes were measured

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manually using a caliper on an individual basis. Q wave was defined as an initial negative deflection of the QRS complex of >30ms in duration and > 0.1 mV in amplitude. (11) Precordial lead with a remnant r wave (< 0.1 mV) was considered as a Q wave. QT duration, Tp-e duration and QRS duration was calculated using the same programme. ST segment elevation was measured at the J point using the same caliper. ‘T wave negativity’ was defined as >0.05 mV negative deflection of T wave from the isoelectric line. Inverted T wave alone in lead aVR, V1 or D3 was not defined as ‘T wave negativity’. Inverted T waves in two or more contiguous leads were defined as ‘T wave negativity’. Angiography was performed using nonionic (Omnipaque 300 [ioheksol]) contrast dye in all patients. LAD osteal portion was defined as branching of the artery from LMCA. The first diagonal branch serves as the

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ACCEPTED MANUSCRIPT boundary between the proximal and mid portion of the LAD. Thus, the portion of the artery prior to the origin of the diagonal is known as the proximal LAD, while the segment below the

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diagonal is the mid LAD. The distal segment of the LAD is the terminal third of the artery. Type of antiplatelet agent added to asetylsalicyclic acid was left to the interventional cardiologist. Clopidogrel, prasugrel and ticagrelor were the available agents used at the

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hospital. The duration and pressure of balloon inflation, the number of inflations, and the choice of interventional equipment, including balloon and stent, were left to the discretion of

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the interventional cardiologist performing the procedure. In-hospital events were evaluated by

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a trained study coordinator.

The study population was divided into tertiles according to their Q/R starting with the

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lowest Q/R.

Definitions

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The primary end points were the incidence of in-hospital mortality. Cardiogenic shock, in-

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hospital target vessel revascularization, stent thrombosis, recurrent MI and major adverse cardiac events (MACE) were also noted. In-hospital mortality was defined as death from any cause during hospitalization. Cardiogenic shock was defined as systolic pressure less than 90 mm Hg or systolic pressure drop greater than or equal to 40 mm Hg for greater than 15 minutes without new-onset arrhythmia, hypovolemia, or sepsis. MACE included death, recurrent MI, stent thrombosis and target vessel revascularization. Hypertension was defined as systolic pressure greater than 140 mm Hg, or diastolic pressure greater than 90 mm Hg or previously diagnosed hypertension. Diabetes mellitus (DM) was defined as use of insulin or anti-diabetic agents in the patient's medical history or a fasting glucose level greater than 126 mg/dL. Hyperlipidemia was defined as serum total cholesterol ≥ 240 mg/dL, serum

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ACCEPTED MANUSCRIPT triglyceride ≥ 200 mg/dL, low-density lipoprotein cholesterol ≥ 130 mg/dL, previously

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diagnosed hyperlipidemia.

Follow-up

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All follow-up data were obtained during patients’ hospitalization period. The primary end point was the incidence of in-hospital mortality. Cardiogenic shock, recurrent MI and MACE

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were also separately evaluated.

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Statistical analysis

In the first step, the study population was divided into tertiles according to Q/R on admission ECG. Three groups were formed accordingly: one with 118 patients (tertile 1) other with 118 patients (tertile 2) and the last with 118 patients (tertile 3). In the second step, baseline

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characteristics were compared among these three groups. Quantitative variables were

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expressed as mean value ± SD. Kolmogorov-Smirnov test was used for testing of normality. All continuous variables showed skewed distributions and compared using the Kruskal Wallis test. Categorical variables were expressed as numbers and percentages, Pearson’s chi-square or Fisher’s exact tests were used to evaluate the differences. Spearman correlation analysis was used for the correlation between LVEF and Q/R, total R, total Q and total ST segment elevation. Logistic regression models for mortality, cardiogenic shock and MACE by precordial total Q amplitude/precordial total R amplitude was used. Two logistic regression multivariable models were used: model I, unadjusted; model II adjusted. The variables covariate in the model II: demographics (age, sex); body mass index; hypertension; diabetes mellitus; hyperlipidemia; current smoking; chronic renal failure; onset-to-door time; door-to-

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ACCEPTED MANUSCRIPT balloon time; first measurement of systolic blood pressure and heart rate; first measurement during hospitalization of the following laboratory values (admission blood urea nitrogen,

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white blood cell count, hemoglobin, CRP, glucose); creatine kinase-MB, troponin I; medication (type of antiplatelet agent) and LVEF. Analyses were performed using Statistical

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Package for Social Sciences software, version 20.0 (SPSS; IBM, Armonk, New York, USA)

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Results

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Baseline characteristics, angiography, laboratory and echocardiography findings

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Baseline characteristics, categorized by admission Q/R, were listed in Table 1. A total of 354 patients (mean age 57.6 ± 12.9; men 82.5%) with first acute anterior MI were included. The patients in tertile 1 had higher prevalence of chronic renal failure compared with other tertiles. (p=0.007). The three groups were similar in terms of hypertension, diabetes mellitus,

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hyperlipidemia, body mass index, smoking, pre-infarction angina and Killip≥3 score.

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Whereas, tertile 3 had significantly higher onset to door time (p<0.001). Systolic blood pressure and diastolic blood pressure were remarkably lower in tertile 2 (p=0.002) and they were highest in tertile 3. Heart rate was significantly higher in tertile 2. Considering culprit artery, LAD mid/distal occlusion was detected to be more frequent in tertile 1. (p=0.004) The other portions of the LAD were detected similar as a culprit lesion between the tertiles. Additional stenosis in other vessels did not differ between tertiles. Percutaneous transluminal coronary angioplasty (PTCA) was performed more frequent in tertile 3. (p=0.019) Stent length and pressure were significantly lower in tertile 1. (<0.001 and 0.002 respectively) Pre-PCI TIMI flow≤1 was detected significantly higher in tertile 3. (p=0.035) Post-PCI TIMI 1 flow was detected statistically higher in tertile 3. (p=0.005) Admission troponin I and CKMB serum

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ACCEPTED MANUSCRIPT levels were notably higher in tertile 3. (<0.001 and 0.023 respectively) LVEF was notably lower in tertile 3. (p<0.001) GRACE score was notably higher in tertile 3. (p<0.001) Figure 1

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shows the ECG examples of the tertiles. Figure 1a presents all leads (V1-6) with R waves. Figure 1b presents Q waves in V1-3, R waves in V4-6. Figure 1c presents Q waves in V1-6, R waves in V5-6.

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Electrocardiography findings

Table 2 summarized electrocardiographic findings. Atrial fibrillation at admission did not

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differ between the tertiles. V1Q, V2Q, V3Q, V4Q, V5Q and V6Q amplitudes in ECG were

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remarkably higher in tertile 3. (p<0.001) Whereas V1R, V2R, V3R, V4R, V5R and V6R amplitudes were statistically higher in tertile 1. (p<0.001) Total ST segment elevation

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amplitude and total precordial Q wave amplitude were notably higher in tertile 3. (p<0.001 and p<0.001) Total precordial R wave amplitude was notably higher in tertile 1. (p<0.001) In-hospital outcomes

Outcomes of the patients according to their Q/R were displayed in table 3. All cause

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mortality, cardiogenic shock, recurrent MI and MACE were detected higher in tertile 3.

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(p<0.001, p<0.001, 0.007 and p<0.001 respectively) ROC analysis showed that the best cutoff value of the Q/R to predict in-hospital mortality was 1.5 with 72% sensitivity and 78% specificity (AUC: 0.80; 95% CI: 0.71–0.89; p < 0.001), the best cut-off value of the GRACE score to predict in-hospital mortality was 140 with 81% sensitivity and 84% specificity (AUC: 0.89; 95% CI: 0.83–0.94; p < 0.001), the best cut-off value of the total R wave to predict survival was 1.56 mV with 62% sensitivity and 58% specificity (AUC: 0.68; 95% CI: 0.59– 0.77; p < 0.001) and the best cut-off value of the total Q wave to predict in-hospital mortality was 1.76 mV with 69% sensitivity and 69% specificity (AUC: 0.69; 95% CI: 0.58–0.76; p < 0.001) (figure 2) Table 4 listed unadjusted and adjusted logistic regression for in-hospital events (mortality, cardiogenic shock and major adverse cardiac events) by tertiles. Tertile 3

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ACCEPTED MANUSCRIPT had 6.9 times higher mortality rates (95% CI, 2.1–41.1) than tertile 1, which had lower rates and was used as the reference. Cardiogenic shock of tertile 3 had 3.2 times higher rates (95%

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CI, 1.6–14.2) than tertile 1, which had the lower rates and was used as the reference. MACE of tertile 3 had 3.6 times higher rates (95% CI, 1.6–9.6) than tertile 1, which had the lower rates and was used as the reference.

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In table 5, spearman correlation analysis revealed a correlation between Q/R in admission ECG and LVEF. (Rho:0.339, p<0.001) The correlation was stronger than others such as total

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Q amplitude, total R amplitude and precordial ST elevation. Figure 3 indicated scatterplot of

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the correlation between LVEF and Q/R. (Rho:0.339, p<0.001)

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Discussion

This is a pilot study presenting Q/R in admission ECG in patients with first acute anterior MI treated with PPCI. Our study demonstrated Q/R in admission ECG as an independent

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prognostic factor for prediction of in-hospital mortality, cardiogenic shock and MACE. The

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predictive value of Q/R in admission ECG of patients with MI is up-and-coming. There was a correlation between LVEF and precordial total R wave, total Q wave, ST segment elevation and Q/R. The strongest correlation was between LVEF and Q/R. There were several ECG based studies in the literature applied to ST segment elevation MI patients. One of the issues reported by those studies was Q and R wave alterations. Q waves on initial ECG were more commonly observed in patients with anterior infarction. (3) The investigations on R wave amplitude were also analyzed in experimental animals or in patients with anterior MI. (2,7,12,13) Thus, anterior MI is more appropriate to investigate the prognostic value of Q/R in precordial derivations which were more in number when compared to other MI types.

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ACCEPTED MANUSCRIPT Q waves at admission do not mean irreversible necrosis but they were demonstrated to have adverse prognosis independent of onset-to-door time. (3) Initial Q waves were proved to

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be representative of lack of left ventricle recovery. (14) A close relation between initial Q waves and no-reflow after PPCI was also reported. (15) Besides, when patients with Q and non-Q wave anterior MI were compared, total left ventricular long axis amplitude of motion

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was reduced in Q wave MI. (16) Therefore one of the reasons of adverse prognostic effect of Q wave may be due to its effect on electromechanical function. R wave has a different

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biphasic response after transmural ischemia when compared to Q wave. In pigs after five

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minutes of LAD ligation, R waves were demonstrated to be enlarged in ECG leads with ST segment elevation. (17) Similarly ECGs were recorded during balloon inflations in coronary

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arteries of fifty patients and it was proved that R wave amplitude notably increased during balloon inflations when compared to baseline ECGs. (12) On the other hand, if the transmural ischemia duration lengthens, R wave amplitude significantly decreases. Two hours and eight weeks after Rhesus monkeys’ LAD was ligated, R waves were measured. Precordial R waves

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were significantly decreased when compared to initial ones. R wave amplitude changes were

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defined to be correlative with the myocardial infarction size. (13) The prognostic power of Q/R in anterior MI arises out of Q and R waves’ amplitude response to transmural ischemia. When onset-to-balloon time is short, the probability of Q wave appearance in precordial leads is low and increase in R wave amplitude is more likely. Therefore Q/R decreases. When the duration lengthens, Q wave frequently appears and R wave regresses in the initial ECG. Therefore Q/R increases. Patients’ features regarding pre-PCI TIMI flow≤1 and LAD mid/distal as a culprit artery supported the prognostic value of Q/R. The correlation between Q/R and LVEF also displayed the reliability of this novel parameter. Higher creatine kinase-MB and troponin I serum levels were also representative of greater ischemic myocardial tissue in patients with higher Q/R.

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ACCEPTED MANUSCRIPT Moreover we tested the prognostic value of Q/R by the help of internationally accepted index, GRACE score. (18) When compared to GRACE score, which includes demographic,

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laboratory and clinical findings, Q/R preserved its prognostic value despite its simplicity.

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Study Limitations

The current study has several limitations. Firstly; this was a single centre and observational

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study; however it was conducted in a high volume interventional centre for PPCI and all

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consecutive patients who met the criteria were included, thus limiting selection bias. Some of the patients who had previous MI, PCI or CABG were excluded because their precordial

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ECGs may have been affected before the reference event.

Conclusion

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Our pilot study indicated that Q/R is an independent prognostic factor for in-hospital

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mortality, cardiogenic shock and MACE of patients with first acute anterior MI. This result confirmed that precordial Q and R wave amplitudes are important when considering inhospital outcomes in patients with first acute anterior MI. Further investigations on independent multicentre cohorts including other MI types should be performed in order to validate our findings.

Compliance with Ethical Standards This article does not contain any studies with human participants or animals performed by any of the authors.

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ACCEPTED MANUSCRIPT Conflict of interest

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The authors have no conflicts of interest to disclose.

Figure legends

1) Figure 1A presents example ECG from tertile 1, figure 1B presents ECG from tertile 2,

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figure 1C presents ECG from tertile 3. Figure 1a presents all leads (V1-6) with R waves. Figure 1b presents Q waves in V1-3, R waves in V4-6. Figure 1c presents Q waves in V1-6, R

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waves in V5-6.

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2) ROC analysis showed that the best cut-off value of the Q/R to predict in-hospital mortality was 1.5 with 72% sensitivity and 78% specificity (AUC: 0.80; 95% CI: 0.71–0.89; p < 0.001),

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the best cut-off value of the GRACE score to predict in-hospital mortality was 140 with 81% sensitivity and 84% specificity (AUC: 0.89; 95% CI: 0.83–0.94; p < 0.001), the best cut-off value of the total R wave to predict survival was 1.56 mV with 62% sensitivity and 58% specificity (AUC: 0.68; 95% CI: 0.59–0.77; p < 0.001) and the best cut-off value of the total Q

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wave to predict in-hospital mortality was 1.76 mV with 69% sensitivity and 69% specificity

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(AUC: 0.69; 95% CI: 0.58–0.76; p < 0.001) 3) Scatterplot of the correlation between LVEF and Q/R. (rho:0.339, p<0.001)

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ACCEPTED MANUSCRIPT References

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1) Hamdan A, Kornowski R, Solodky A, Fuchs S, Battler A, Assali AR. Predictors of left ventricular dysfunction in patients with first acute anterior myocardial infarctionundergoing

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primary angioplasty. Isr Med Assoc J. 2006 Aug;8(8):532-5.

2) Tsai TH, Sun CK, Chung WJ, Lin YC, Leu S, Hussein H, Chen YL, Chung SY, Chai

NU

HT, Chua S, Fu M, Yip HK. Prognostic value of R-wave voltage in patients with anterior wall

MA

ST-segment elevation myocardial infarction undergoing primary percutaneous coronary

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intervention. Int Heart J. 2010;51(5):325-30.

3) Kumar S, Hsieh C, Sivagangabalan G, Chan H, Ryding AD, Narayan A, Ong AT, Sadick N, Kovoor P. Prognostic impact of Q waves on presentation and ST resolution in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary

AC

CE

intervention. Am J Cardiol. 2009 Sep 15;104(6):780-5.

4) Kotoku M, Tamura A, Abe Y, Kadota J. Significance of a prominent Q wave in lead negative aVR (-aVR) in acute anterior myocardial infarction. J Electrocardiol. 2010 MayJun;43(3):215-9.

5) Wong CK, French JK, Aylward PE, Frey MJ, Adgey AA, White HD. Usefulness of the presenting electrocardiogram in predicting successful reperfusion with streptokinase in acute myocardial infarction. Am J Cardiol. 1999 Jan 15;83(2):164-8.

14

ACCEPTED MANUSCRIPT 6)Phibbs

B, Marcus

F, Marriott

Q wave myocardial infarction:

HJ, Moss

A, Spodick

a meaningless distinction.

J

DH. Am

Q-wave versus nonColl

Cardiol. 1999

RI PT

Feb;33(2):576-82.

7) David D, Naito M, Chen CC, Michelson EL, Morganroth J, Schaffenburg M. R-

SC

wave amplitude variations during acute experimental myocardial ischemia: an inadequate

NU

index for changes in intracardiac volume. Circulation. 1981 Jun;63(6):1364-71.

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J 2007; 28:2525–2538.

MA

8) Thygesen K, Alpert JS, White HD. Universal definition of myocardial infarction. Eur Heart

9) Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I. Recommendations for quantitation of the left ventricle by two dimensional echocardiography. American Society of Echocardiography Committee on

CE

Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc

AC

Echocardiogr 1989;2:358-367.

10) Oh JK, Hagler DJ, Cabalka A, Reeder GS, Cetta Jr F, Seward JB. Transesophageal and intracardiac echocardiography. In: Oh JK, Seward JB, Tajik AJ, editors. The echomanual. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006. p. 29–58.

11) Nijveldt R, van der Vleuten PA, Hirsch A, Beek AM, Tio RA, Tijssen JG, et al. Early electrocardiographic findings and MR imaging-verified microvascular injury and myocardial infarct size. JACC Cardiovasc Imaging 2009;2:1187–94.

15

ACCEPTED MANUSCRIPT 12)

Sinno

MC, Kowalski

M, Kenigsberg

DN, Krishnan

SC, Khanal

S.

R-

wave amplitude changes measured by electrocardiography during early transmural ischemia. J

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Electrocardiol. 2008 Sep-Oct;41(5):425-30.

13) Sun X, Cai J, Fan X, Han P, Xie Y, Chen J, Xiao Y, Kang YJ. Decreases in ischemic

SC

electrocardiographic R-wave amplitude and QT interval predict myocardial

infarction in Rhesus monkeys with left anterior descending artery ligation. PLoS One. 2013

MA

NU

Aug 13;8(8):e71876

14) Bigi R, Mafrici A, Colombo P, Gregori D, Corrada E, Alberti A, De Biase A, Orrego

PT ED

PS, Fiorentini C, Klugmann S. Relation of terminal QRS distortion to left ventricular functional recovery and remodeling in acute myocardial infarction treated with primary angioplasty. Am J Cardiol. 2005 Nov 1;96(9):1233-6

CE

15) Iwakura K, Ito H, Kawano S, Shintani Y, Yamamoto K, Kato A, Ikushima M, Tanaka

AC

K, Kitakaze M, Hori M, Higashino Y, Fujii K. Predictive factors for development of the noreflow phenomenon in patients with reperfused anterior wall acute myocardial infarction. J Am Coll Cardiol. 2001 Aug;38(2):472-7.

16)

O'Sullivan

CA, Ramzy

IS, Duncan

A, Li

W, Henein

the Q wave infarct on left ventricular electromechanical function.

Int

MY.

The effect of

J

Cardiol. 2003

Nov;92(1):71-6.

17)

Wiegerinck

RF, Gálvez-Monton

C, Jorge

E, Martínez R, Ricart

E, Cinca

J.

Changes in QRS duration and Rwave amplitude in electrocardiogram leads with ST segmentel

16

ACCEPTED MANUSCRIPT evation differentiate epicardial and transmural myocardial injury. Heart Rhythm. 2010

18)

GRACE

Investigators.

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Nov;7(11):1667-73.

Rationale

and

design

of

the

GRACE

(Global Registry of Acute Coronary Events) Project: a multinational registry of patients

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CE

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MA

NU

SC

hospitalized with acute coronary syndromes. Am Heart J. 2001 Feb;141(2):190-9.

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ACCEPTED MANUSCRIPT Table 1 Baseline characteristics,angiography, laboratory and echocardiography findings

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GRACE Score Echocardiography parameters LVEF, % IVS PW LVEDD LVESD RV TAPSE RV S’ velocity, cm/s PASP, mmHg Mitral E Mitral A Mitral E’ Mitral A’ EFT Left atrial volume index Left ventricle mass index

59±12 98 (83.1) 27.4±3.5 46 (40.7) 32 (27.1) 10 (8.5) 82 (69.5) 4 (3.4) 56 (47.5) 8 (6.8) 60 (50.8) 4.25±3.46 29.5±39.1 6 (5.1)

0.090 0.578 0.325 0.122 0.035 0.646 0.333 0.007 0.138 0.039 0.956 <0.001 0.126 0.338

133.2±27.5 79.1±16.2 80.5±14.4

125.5±33.2 72.1±19.9 89.0±22.7

138.0±28.7 80.9±16.8 87.9±14.9

0.002 0.004 0.001

2 (1.7) 8 (6.8) 68 (57.6) 52 (44.1)

2 (1.7) 12(10.2) 70(59.3) 38 (32.2)

0 (0.0) 12 (10.2) 80 (67.8) 28 (23.7)

0.364 0.577 0.228 0.004

16 (13.6) 22 (18.6) 26 (22.0) 94 (79.7) 1.74±0.9 11.8±6.0 11.7±6.1 82 (71.9) 14 (11.9) 23.8±10.4 13.3±4.6 24 (20.3) 94 (79.7)

10 (8.5) 24 (20.3) 24 (20.3) 106 (89.8) 1.92±0.6 13.7±5.0 12.8±4.2 88 (75.9) 6 (5.1) 23.9±7.5 13.0±3.4 18 (15.3) 106 (89.8)

0.329 0.418 0.934 0.019 0.416 0.058 0.376 0.180 0.168 <0.001 0.002 0.152 0.035

4 (3.4) 0 (0.0) 14 (11.9) 100( 84.7) 4 (3.4) 40 (33.9)

4 (3.4) 2 (1.7) 12 (10.2) 100 (84.7) 2 (1.7) 42 (35.6)

2 (1.7) 8 (6.8) 12 (10.2) 96 (81.4) 2 (1.7) 38 (32.2)

0.663 0.005 0.889 0.719 0.600 0.860

44 (37.3) 60 (50.8) 14 (11.9)

34 (28.8) 66 (55.9) 18 (15.3)

38 (32.2) 54 (45.8) 26 (22.0)

0.377 0.295 0.099

13.6 ± 5.4 10.7 ± 4.0 13.5 ± 1.5 167.0 ± 123.0 17.1 ± 15.4 0.85 ± 0.26 150.3 ± 208.9 16.7 ± 19.6 2.99 ± 4.31

13.7 ± 4.3 11.5 ± 4.1 13.3 ± 1.8 175.1 ± 80.4 14.2 ± 4.8 0.81 ± 0.20 144.6 ± 130.6 23.9 ± 21.0 4.65 ± 5.67

13.3 ± 3.4 10.5 ± 3.0 13.2 ± 1.9 164.4 ± 75.3 13.7 ± 3.8 1.00 ± 0.30 158.1 ± 130.6 24.1 ± 20.6 3.82 ± 4.69

0.806 0.207 0.296 0.116 0.537 0.919 0.023 <0.001 0.076

99.1 ± 29.2

121.9 ± 34.8

130.5 ± 23.7

<0.001

43.0 ± 7.44 0.96 ± 0.19 0.97 ± 0.18 4.84 ± 0.51 3.42 ± 0.55 23 ± 3 14.2 ± 2.6 20.4 ± 10.5 66.9 ± 18.6 78.1 ± 19.8 9.9 ± 3.3 12.6 ± 3.4 0.39 ± 0.15 27.5 ± 10.1 104.7 ± 8.0

39.6 ± 7.0 1.00 ± 0.19 1.00 ± 0.18 4.96 ± 0.54 3.61 ± 0.56 22 ± 4 14.4 ± 3.6 22.0 ± 13.2 69.7 ± 23.0 74.4 ± 21.9 9.9 ± 3.8 12.8 ± 4.0 0.41 ± 0.11 26.4 ± 8.8 106.6 ± 10.9

37.1 ± 5.9 1.00 ± 0.16 1.01 ± 0.16 4.91 ± 0.52 3.54 ± 0.60 24 ± 2.2 13.5 ± 2.6 21.5 ± 10.0 69.0 ± 19.6 75.2 ± 23.3 9.8 ± 3.6 12.0 ± 4.1 0.42 ± 0.13 29.4 ± 11.9 109.0 ± 16.3

<0.001 0.035 0.129 0.517 0.137 0.048 0.213 0.473 0.642 0.349 0.767 0.120 0.132 0.351 0.529

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10 (8.5) 30 (25.4) 24 (20.3) 90 (76.3) 1.84±0.9 12.2±5.8 11.6±5.6 74 (64.9) 12 (10.2) 19.9±9.6 12.1±4.9 30(25.4) 92 (78.0)

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57±12 100 (84.7) 28.3±5.2 46 (39.0) 26 (22.0) 8 (6.8) 86 (72.9) 2 (1.7) 54 (45.8) 18 (15.3) 60 (50.8) 3.62±3.35 25.1±20.9 12 (10.2)

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55±13 94 (79.7) 27.8±4.6 34 (28.8) 16 (13.6) 12( 10.2) 92 (78.0) 12 (10.2) 42(35.6) 8 (6.8) 58 (49.2) 2.77±2.38 37.2±66.3 10 (8.5)

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Age,y Male gender Body mass index Hypertension Diabetes Mellitus Hyperlipidemia Current smoker Chronic Renal Failure Preinfarction Angina CPA Heredity Onset-to-door time, hours Door-to-ballon time, minutes Admission Killip≥3 At admission Systolic blood pressure, mm Hg Diastolic blood pressure, mm Hg Heart rate, beats per minute Infarct related artery LMCA LAD Osteal LAD Proximal LAD Mid/Distal Additional ≥70% stenosis Diagonal CX RCA PTCA Balloon diameter Balloon length Balon pressure, atm Stent(DES) Stent number>1 Stent length Stent pressure, atm Non-compliant ballon usage Pre-PCI TIMI flow≤1 Post-PCI TIMI TIMI 0 TIMI 1 TIMI 2 TIMI 3 Thrombus Aspiration Tirofiban usage Antiplatelet agent Clopidogrel Ticagrelor Prasugrel Admission laboratory variables White blood cell, cells/µL Neutrophil, cells/µL Hemoglobin, g/dL Glucose, (mg/dL) Blood urea nitrogen, (mg/dL) Creatinine, (mg/dL) Creatine kinase-MB, U/L Troponin I, ng/mL CRP, (mg/dL)

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Precordial total Q amplitude/ Precordial total R amplitude T1(n=118) T2(n=118) T3(n=118) p

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ACCEPTED MANUSCRIPT

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Continuous variables are presented as mean ± SD Nominal variables presented as frequency (%). CPA indicates cardiopulmonary arrest; LAD, left anterior descending artery; CX, circumflex artery; RCA, right coronary artery; PTCA, percutanoeus transluminal coronary angioplasty; DES, drug eluting stent; PCI, percutaneous coronary intervention; CRP, C-reactive protein; LVEF, left ventricular ejection fraction; IVS, interventricular septum; PW, posterior Wall ; LVEDD, left ventricular end diastolic diameter; LVESD, left ventricular end systolic diameter; RV, right ventricle; TAPSE, tricuspid annular plane systolic excursion; PASP, pulmonary artery systolic pressure; EFT, epicardial fat tissue.

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ACCEPTED MANUSCRIPT Table 2 Electrocardiography findings

Precordial total Q amplitude/ Precordial total R amplitude T3 (n=118) 4 (3.4) 0.68 ± 0.41 0.75 ± 0.42 0.81 ± 0.57 0.41 ± 0.43 0.10 ± 0.19 0.01 ± 0.07 0.01 ± 0.04 0.00 ± 0.04 0.01 ± 0.05 0.11 ± 0.17 0.31 ± 0.25 0.54 ± 0.25 93.4 ± 12.2 1.38± 0.76 2.79 ± 1.38 1.00 ± 0.54 4.09 ± 4.02 415.2 ± 39.4 95.4 ± 16.9 39 (33.1) 3.87 ± 1.02 4.95 ± 0.95

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T2 (n=118) 2 (1.7) 0.61 ± 0.32 0.49 ± 0.41 0.34 ± 0.41 0.03 ± 0.10 0.01 ± 0.06 0.00 ± 0.02 0.07 ± 0.24 0.08 ± 0.19 0.15 ± 0.23 0.48 ± 0.39 0.70 ± 0.50 0.75 ± 0.39 94.5 ± 14.3 1.09 ± 0.57 1.50 ± 0.77 2.26 ± 1.12 0.72 ± 0.29 413.9 ± 51.9 98.5 ± 22.9 29 (24.6) 2.51 ± 0.91 4.59 ± 1.08

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T1 (n=118) 2 (1.7) 0.36 ± 0.34 0.03 ± 0.07 0.11 ± 0.04 0 0 0 0.08 ± 0.13 0.42 ± 0.37 0.47 ± 0.36 0.86 ± 0.47 1.00 ± 0.43 0.91 ± 0.39 97.2 ± 16.9 1.14 ± 0.62 0.41 ± 0.34 3.76 ± 1.53 0.12 ± 0.09 408.5 ± 47.9 98.2 ± 27.6 24 (20.3) 0.88 ± 0.76 4.53 ± 1.15

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AF V1Q Amplitude, mV V2Q Amplitude, mV V3Q Amplitude, mV V4Q Amplitude, mV V5Q Amplitude, mV V6Q Amplitude, mV V1R Amplitude, mV V2R Amplitude, mV V3R Amplitude, mV V4R Amplitude, mV V5R Amplitude, mV V6R Amplitude, mV QRS duration Precordial total ST elevation Total V1-V6 Q Amplitude, mV Total V1-V6 R Amplitude, mV Total V1-V6 Q / Total V1-V6 R QTC duration, s Tp-e duration, s T-wave negativity in V1-6 Number of Q waves in V1-V6 Number of leads with ST elevation V1-

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V6 Continuous variables are presented as mean ± SD; Nominal variables presented as frequency (%). AF indicates atrial fibrillation; QTc, corrected QT ; Tp-e, T peak to T end.

P 0.600 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 0.119 0.006 <0.001 <0.001 <0.001 0.255 0.793 0.077 <0.001 0.003

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ACCEPTED MANUSCRIPT Table 3 In-hospital outcomes Precordial total Q amplitude/ Precordial total R amplitude T1 (n=118) T2 (n=118) T3 (n=118) P 3 (2.5) 9 (7.6) 4 (3.4) 2 (1.7) 3 (2.5) 7 (5.9)

6 (5.1) 11 (9.3) 7 (5.9) 5 (4.2) 5 (4.2) 12 (10.2)

24 (20.3) 33 (28.0) 12 (10.2) 9 (7.6) 14 (11.9) 30 (25.4)

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In-hospital course All-cause mortality Cardiogenic Shock In-hospital TLR Stent thrombosis Recurrent myocardial infarction MACE

<0.001 <0.001 0.102 0.089 0.007 <0.001

Nominal variables presented as frequency (%). TLR indicates target lesion revascularization; MACE, major adverse cardiac events.

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Continuous variables are presented as median and 25-75 percentiles; nominal variables presented as frequency (%). Mann-Whitney-U test used for continuous variables and Pearson-Chi-Square test used for nominal variables.

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ACCEPTED MANUSCRIPT Table 4 In-hospital event rates and logistic regression models for mortality, cardiogenic shock and MACE by precordial total Q amplitude/precordial total R amplitude.

Precordial total Q amplitude/ Precordial total R amplitude

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T1 T2 T3 In-hospital mortality Number of deaths 3 6 24 Mortality,% 2.5 5.1 20.3 Mortality, OR (%95 CI) Model 1:unadjusted 1[Reference] 2.0 (0.5 – 8.4) 9.7 (2.8 – 33.5) Model 2: adjusted for all covariatesa 1[Reference] 1.5 (0.1 – 9.7) 6.9 (2.1 – 41.1) Cardiogenic Shock Number of events 9 11 33 Events,% 4.9 12.8 28.0 Events, OR (%95 CI) Model 1:unadjusted 1[Reference] 1.2 (0.4 – 3.1) 4.7 (2.1 – 10.3) Model 2: adjusted for all covariatesa 1[Reference] 1.6 (0.4 – 5.7) 3.2 (1.6 – 14.2) MACE Number of events 7 12 30 Events, % 5.9 10.2 25.4 Events, OR (%95 CI) Model 1:unadjusted 1[Reference] 1.7 (0.6 – 4.7) 5.4 (2.2 – 12.8) Model 2: adjusted for all covariatesa 1[Reference] 1.2 (0.4 – 3.6) 3.6 (1.6 – 9.6) Abbreviations: OR, odds ratio. aIncludes demographics (age, sex); body mass index; hypertension; diabetes mellitus; hyperlipidemia; current smoking; chronic renal failure; onset-to-door time; door-toballoon time; first measurement of systolic blood pressure and heart rate; first measurement during hospitalization of the following laboratory values (admission blood urea nitrogen, white blood cell count, hemoglobin, CRP, glucose); creatine kinase-MB, troponin I; medication (type of antiplatelet agent) and left ventricle ejection fraction.

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ACCEPTED MANUSCRIPT Spearman Rank Correlation (R) between ejection fraction and precordial total Q/ precordial total R, precordial total Q, precordial total R, precordial ST segment elevation R 0.339 0.286 0.260 0.197

P <0.001 <0.001 <0.001 <0.001

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Variable Ejection fraction and precordial total Q/R Ejection fraction and precordial total Q Ejection fraction and precordial total R Ejection fraction and precordial ST elevation

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Figure 1

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Figure 2

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Figure 3

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ACCEPTED MANUSCRIPT Highlights

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Q/R in admission ECG in patients with first acute anterior MI treated with PPCI provide an independent prognostic marker of in-hospital outcomes

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