Association between prolonged PR intervals and significant coronary artery disease in patients with non-ST elevation myocardial infarction and unstable angina

Maryam Nabati; Bahareh Kalantari; Zahra Dehghan; Jamshid Yazdani; Mojdeh Dabirian

doi:10.4103/rcm.rcm_1_17

ORIGINAL ARTICLE

Year : 2020 | Volume : 9 | Issue : 1 | Page : 6-9

Association between prolonged PR intervals and significant coronary artery disease in patients with non-ST elevation myocardial infarction and unstable angina

Maryam Nabati¹, Bahareh Kalantari¹, Zahra Dehghan¹, Jamshid Yazdani², Mojdeh Dabirian¹
¹ Department of Cardiology, Faculty of Medicine, Fatemeh Zahra Teaching Hospital, Cardiovascular Research Center, Mazandaran University of Medical Sciences, Sari, Iran
² Department of Biostatistics, Cardiovascular Research Center, Faculty of Health, Mazandaran University of Medical Sciences, Sari, Iran

Date of Submission	01-Oct-2017
Date of Decision	13-Nov-2017
Date of Acceptance	09-Jan-2020
Date of Web Publication	24-Apr-2020

Correspondence Address:
Dr. Maryam Nabati
Department of Cardiology, Faculty of Medicine, Fatemeh Zahra Teaching Hospital, Cardiovascular Research Center, Mazandaran University of Medical Sciences, Sari
Iran

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/rcm.rcm_1_17

Abstract

Objectives: The purpose of this study was to assess the association between a prolonged PR interval and significant coronary artery disease (CAD) in patients who were acutely admitted with unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI). Background: Prolongation of the electrocardiographic PR interval occurs frequently in clinical practice. Few studies to date have evaluated the association between prolonged PR intervals and significant CAD in hospitalized patients with NSTEMI and unstable angina. Methodology: PR interval was measured in 205 patients with NSTEMI or unstable angina, and the patients were divided into those with normal (<200 ms) and prolonged PR interval (≥200 ms). We performed echocardiography and coronary angiography within 48–72 h after hospitalization in all patients. Results: A prolonged PR interval (%(>([0-9]+)200 ms) was present in 96 patients (46.8%). This finding was statistically significantly associated with significant CAD (P = 0.024). In addition, these patients had a trend toward higher Gensini scores (P = 0.093) and a higher frequency of left main coronary artery or three-vessel CAD (P = 0.069). Conclusion: Our study showed that a prolonged PR interval is independently associated with significant CAD in patients with acute coronary syndrome, in contrast with earlier beliefs.

Keywords: Acute coronary syndrome, electrocardiography, first-degree atrioventricular block, myocardial infarction, PR interval

How to cite this article:
Nabati M, Kalantari B, Dehghan Z, Yazdani J, Dabirian M. Association between prolonged PR intervals and significant coronary artery disease in patients with non-ST elevation myocardial infarction and unstable angina. Res Cardiovasc Med 2020;9:6-9

How to cite this URL:
Nabati M, Kalantari B, Dehghan Z, Yazdani J, Dabirian M. Association between prolonged PR intervals and significant coronary artery disease in patients with non-ST elevation myocardial infarction and unstable angina. Res Cardiovasc Med [serial online] 2020 [cited 2021 Mar 7];9:6-9. Available from: https://www.rcvmonline.com/text.asp?2020/9/1/6/282432

Introduction

The PR interval describes electrical conduction from the sinus node to the ventricles. First-degree atrioventricular (AV) block, which is considered prolongation of PR interval >200 ms, is commonly observed.^[1] It measures the period needed for electrical impulses which are originated from sino-atrial node to conduct into the atrium, AV node, and His bundle, until the beginning of QRS complex. Some serious conditions can result in the prolongation of PR interval, such as defective internal conduction of atrium, increase in vagal tone which can prolong AV nodal conduction, involvement of AV node or His Bundle by conduction disturbance, and prescription of antiarrhythmic drugs.^[2] Previous studies demonstrated that healthy patients with first-degree AV block are at low risk for adverse cardiovascular accidents, and it does not have any prognostic significance.^[3] Otherwise, recent studies have also reported that a prolonged PR interval is associated with a high probability for developing atrial fibrillation (AF), needing pacemaker, and an increased risk for mortality among asymptomatic persons.^[1] Furthermore, a cohort study has shown a relationship between PR interval and heart failure (HF) and AF in older patients. An association has been found between prolonged PR interval with adiposity, increased waist circumference, and insulin resistance, all of which can increase the risk of developing HF. A prolonged PR interval is also a marker of atrial electrical and structural remodeling that may make elderly patients more prone to HF.^[4] To the best of our knowledge, the prognostic significance of prolonged PR interval has not been assessed in patients who were hospitalized with unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI). Hence, we investigated the association between a prolonged PR interval and the atherosclerosis severity in hospitalized patients with acute coronary syndrome (ACS).

Methodology

We performed a single-blind, historical cohort study on 205 patients (range 34–81 years), who were hospitalized with ACS within 24 h from experiencing angina pectoris to the emergency department of Fatemeh Zahra Hospital between October 2014 and November 2015. We performed this study in accordance with the guidelines of the Helsinki declaration after approval from the ethics committee of our hospital. Eighty-nine (43.4%) patients were diagnosed with acute NSTEMI and the remainder were diagnosed with unstable angina. All patients underwent a standard 12-lead electrocardiogram (ECG), the findings of which were recorded within 30 min of emergency room arrival. The patients were placed in the supine position, with the ECG paper speed of 50 mm/s, calibrated to 1 mV/10 mm. The PR interval was determined as the interval from the beginning of the P-wave to the end point of PR segment in bipolar limb lead with the most prolonged PR interval. The PR interval was determined by two blinded internal medicine physicians not involved in care of the patients. A PR interval of <200 ms was considered to be normal. To determine the reproducibility of the electrocardiographic measurements, PR interval was measured in ten randomly selected patients (according to systematic sampling method) by which interobserver correlation coefficients were determined. Again, the next day, we performed these measurements in the same patients for determining intraobserver correlation coefficients. We showed an interobserver correlation coefficient of 0.91 and an intraobserver correlation coefficient of 0.93 in these patients.

The patients were divided into two groups, based on baseline PR intervals that were normal (<200 ms) or prolonged (≥200 ms). Exclusion criteria were missing or unreadable ECG, unreadable PR intervals, left bundle-branch block (LBBB), preexcitation, higher-degree AV block, AF, use of antiarrhythmic drugs, known valvular or congenital heart disease, cardiomyopathies, ECG features of left ventricular hypertrophy, and ST elevation (STE) ≥0.1 mV in each lead except aVR and V1. Hypertension (HTN) was determined as systolic blood pressure (BP) ≥140 mmHg, a diastolic BP ≥90 mmHg, and/or self-reported use of antihypertensive agents.^[5] Diabetes mellitus (DM) was determined according to the criteria of the American Diabetes Association or need to insulin or oral hypoglycemic medications.^[6] Family history (FH) of coronary artery disease (CAD) was determined as having a first-degree relative (male <55 years or female <65 years) with a history of cardiac death or coronary atherosclerosis.^[7] Hyperlipidemia (HLP) was defined as total blood cholesterol levels above 5.5 mmol/L and HDL-cholesterol levels <1.0 mmol/L in males, or <1.1 mmol/L in females.^[8]

Echocardiography

After admission, transthoracic echocardiography was performed for all patients by Vivid S5 (GE Healthcare, Wauwatosa, WI, USA) with a 1–3 MHz transducer. Left ventricular ejection fraction was defined as the end-diastolic volume (EDV) minus the end-systolic volume divided by the EDV from biplane apical two- and four-chamber views using a modified Simpson's technique.

Coronary angiographic data

All patients underwent coronary angiography by Siemens AG, Medical Solutions, Erlangen, Germany, in <3 days. One cardiologist who was blinded to the patients' data reported all angiograms. Significant CAD was defined as >50% stenosis in the left main coronary artery or at least one coronary artery stenosis of >70%.^[9] Furthermore, atherosclerosis severity was measured by the Gensini score.^[10]

Definitions

The ACS diagnosis was established according to the current standards of the European Society of Cardiology.^[11] Patients with acute myocardial infarction (MI) who were admitted within 24 h after the onset of angina and did not have STE ≥0.1 mV in any leads except aVR or V1 or LBBB were considered. The diagnosis of NSTEMI was based on the presence of angina and increase in the serum levels of creatine kinase-MB (CK-MB) or cardiac troponin I (TnI) over the upper limits of normal (25 IU/L and 0.04 ng/mL, respectively). We measured TnI plasma levels by a mini-VIDAS^® analyzer (BioMerieux, Yunycom, Beograd, Serbia) by the chemiluminescence immunoassay technique, with a measurement range of 0.01–30 μg/L, and CK-MB plasma levels by an autoanalyzer (Erba Mannheim, London, England), which was based on the direct measurement of CK-MB enzymatic activity by a Pars Azmoon kit, Tehran, Iran. Cardiac enzyme activities were measured at 4–6 h intervals during the first 48 h. Unstable angina was considered when there was no detectable release of the enzymes and biomarkers of myocardial necrosis. Baseline characteristics were compared between the two groups.

Data analysis

We displayed continuous variables as mean ± standard deviation and for evaluating intergroup differences, t-test was used. Furthermore, Chi-square and Fisher's exact tests were used for comparing categorical variables between them. P < 0.05 was considered statistically significant. All statistical analyses were done by SPSS/(Predictive Analytics SoftWare) Statistics 18 (SPSS Inc., Chicago, IL, USA). The sample size was calculated by the studies that had been done previously.^[4]

Results

The study enrolled 205 patients with ACS, including 89 (43.4%) patients with acute NSTEMI. The mean patient age was 58.2 ± 10.7 years (range: 34–81 years), and 51% were male. A total of 117 (56.8%) patients were younger than 60 years. The most common CAD risk factor was HTN (52.9%). Less frequent risk factors were HLP (37.9%), DM (35%), and FH (9.2%). Nearly 16.1% of the patients were previously on beta-blocker therapy. PR intervals were not statistically significantly different between patients regardless of previous beta-blocker therapy (PR interval of 183.3 ± 40.1 ms with beta-blocker history and 180.2 ± 32.1 ms without, P = 0.72).

A prolonged PR interval >200 ms was present in 96 patients (46.8% of the patients). This was statistically significantly associated with significant CAD (P = 0.024). In addition, these patients had a trend toward higher Gensini scores (P = 0.093) and higher frequencies of left main or three-vessel CAD (P = 0.069). The frequency of major CAD risk factors and other characteristics of patients in each group are displayed in [Table 1] and [Table 2] [Figure 1]. No significant difference was observed for common cardiovascular risk factors such as age, DM, HLP, HTN, FH, and sex between the two groups.

Table 1: Demographics, measures of common cardiovascular risk factors, and baseline characteristics of the study population categorized by the presence or absence of prolonged PR interval

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Table 2: Creatine kinase-MB and Tn-I levels and coronary angiographic data of patients in the study groups

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Figure 1: Correlation between prolonged PR interval and presence of significant coronary artery disease (P = 0.024)

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Discussion

We found a significant association between prolonged PR interval (> 200 ms) and the presence of significant CAD in patients with ACS. Furthermore, we showed that this ECG pattern is associated with trends toward higher Gensini scores and higher frequencies of left main or three-vessel CAD. In 2014, Rijnbeek et al. showed that PR interval increases with age. They determined normal upper limits of 200 ms for persons aged <60 years old and 220 ms for those aged 60 or over. The potential mechanism of the age-dependent change in PR interval may be changing topography of the heart in relation to the thorax and diaphragm, change in orientation of the volume conductor (skin, subcutaneous fat, and lung parenchyma), or alterations of cardiac configuration and intracardiac conduction.^[12] In our study, 117 (56.8%) patients were younger than 60 years. Therefore, our patients were divided into two groups according to normal or prolonged baseline PR intervals, with prolonged PR interval defined as a PR interval ≥200 ms. ECG has considerable value in prognostic classification and handling of patients with NSTEMI and unstable angina. Only a few studies, with inconsistent data, have assessed the prognostic value of PR prolongation in these patients.

Prolonged PR interval is usually a consequence of delay in AV nodal conduction that is highly dependent on autonomic tone modulation. Otherwise, a prolonged PR interval may also be due to disturbance in the conduction of the His-Purkinje system, a condition which is usually seen in the background of myocardial disease.^[3] Infra-Hisian disease is a diagnosis often considered in the setting of Mobitz Type 2 second-degree AV block or third-degree AV block. Otherwise, it may be an unusual source of first-degree AV block. On the other hand, prolonged PR interval in the setting of ischemic heart disease can be a manifestation of more widespread ischemic involvement of the heart. Indeed, larger burden of ischemia in these patients can involve the conduction system and lead to fatal outcome. Higher prevalence of prolonged PR interval in patients with previous inferior MI and with acute ischemia of atrium can be a probable explanation.^[2] In our study, patients with prolonged PR intervals had an increased risk of significant CAD and higher prevalence of previous MI. Few prior studies have determined PR intervals in patients with ACS.

Conclusion

Our study showed that a prolonged PR interval has an independent association with significant CAD in patients with ACS, which is probably not as benign as previously thought. Indeed, it means that these patients may be at a greater risk that warrants a more careful approach.

Study limitations

We did not evaluate long-term outcomes. Another limitation of our study was the small sample size. Furthermore, data were acquired from a single center.

Acknowledgments

This study was a postgraduate thesis by Dr. Bahareh Kalantari. The authors would like to thank all of the patients who were enrolled in this study as well as the staff at the Fatemeh Zahra Hospital, Sari, Iran.

Financial support and sponsorship

Financial support was obtained from the Research Council of the Mazandaran University of Medical Sciences for Dr. Maryam Nabati, Assistant Professor, Fellowship of Echocardiography.

Conflicts of interest

There are no conflicts of interest.

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