There is No Difference in the Incidence of Cardiovascular Events in Patients with Pneumonia Due to Influenza or Pneumonia Due to Other Etiologies: Results from the Rapid Empiric Treatment with Oseltamivir Study (RETOS) Jorge Perez, MD 1 ; Daniel Curran, MD 1 ; Swetha Kadali, MD 1 ; Katherine Rivera, MD 1 ; Martin Gnoni, MD 1 ; Rehab Abdelfattah, MD, MPH 1 ; Humberto Mochizuki, MD 1 ; Daisy Azaña, MD 1 ; Julio Ramirez, MD 1 ; Arnold Forest, DO 1. Division of Infectious Diseases, University of Louisville 1. INTRODUCTION RESULTS (cont’d)  Cardiovascular diseases, influenza, and pneumonia are leading causes of morbidity and mortality worldwide. Cardiovascular events (CVE) are common during the clinical course of pneumonia. 1  Development of a cardiovascular event in a hospitalized patient with pneumonia may produce a significant decline in the clinical status.  A severe cardiovascular event may be the primary determinant of clinical failure in a patient with pneumonia. 1  Investigators have documented an increased incidence of cardiovascular events and associated mortality during the influenza season. 2-6  Patients with influenza pneumonia are at high risk for cardiovascular events. 7-9  It is unknown if cardiovascular events are primarily due to the influenza virus or are due to any form of pulmonary infection.  The objective of this study was to compare the incidence of cardiovascular events in patients with pneumonia due to influenza or pneumonia due to other etiologies. 1.Corrales-Medina VF, Musher DM, Shachkina S, Chirinos JA. Acute pneumonia and the cardiovascular system. Lancet. 2013;381(9865): Guan X, Yang W, Sun X, Wang L, Ma B, Li H, et al. Association of influenza virus infection and inflammatory cytokines with acute myocardial infarction. Inflamm Res Jun;61(6): Loomba RS, Aggarwal S, Shah PH, Arora RR. Influenza vaccination and cardiovascular morbidity and mortality: analysis of 292,383 patients. J Cardiovasc Pharmacol Ther Sep;17(3): Warren-Gash C, Hayward AC, Hemingway H, Denaxas S, Thomas SL, Timmis AD, et al. Influenza infection and risk of acute myocardial infarction in England and Wales: a CALIBER self- controlled case series study. J Infect Dis Dec 1;206(11): Song BG, Wi YM, Lee YJ, Hong CK, Chun WJ, Oh JH. Clinical features in adult patients with in-hospital cardiovascular events with confirmed 2009 Influenza A (H1N1) virus infection: comparison with those without in-hospital cardiovascular events. J Chin Med Assoc Sep;75(9): Phrommintikul A, Kuanprasert S, Wongcharoen W, Kanjanavanit R, Chaiwarith R, Sukonthasarn A. Influenza vaccination reduces cardiovascular events in patients with acute coronary syndrome. Eur Heart J Jul;32(14): Warren-Gash C, Smeeth L, Hayward AC. Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review. Lancet Infect Dis Oct;9(10): Dvorakova A, Poledne R. Influenza--a trigger for acute myocardial infarction. Atherosclerosis Feb;172(2): Lippi G, Franchini M, Favaloro EJ. Influenza and cardiovascular disease: does swine-origin, 2009 H1N1 flu virus represent a risk factor, an acute trigger, or both? Semin Thromb Hemost Feb;36(1): Study Design: This was a secondary analysis of the Rapid Empiric Treatment with Oseltamivir Study (RETOS) database. Hospitalized patients with diagnosis of community-acquired pneumonia (CAP) were included in the analysis.  Definition of CAP: A new infiltrate on x-ray or CT along with one of the following; 1) Temperature > 100F° or cells/mm3, leukopenia 10% band forms per microliter.  Definition of CAP due to Influenza: All criteria for CAP were met, and the patient had a positive nasopharyngeal swab with influenza identified via PCR. Definitions for Cardiovascular Events:  Arrhythmias: (1) atrial flutter, atrial fibrillation, ventricular tachycardia; (2) atrial fibrillation; (3) new-onset or worsening supraventricular arrhythmias and ventricular bigeminy/tachycardia; or (4) atrial fibrillation, atrial flutter, supraventricular tachycardia, multifocal atrial tachycardia, ventricular tachycardia, or ventricular fibrillation.  Heart failure: New or worsened CHF defined by Framingham criteria.  Acute Myocardial Infarction (AMI): (1) a typical increase and gradual decrease in biochemical markers of myocardial necrosis and ischemic symptoms, development of pathologic Q waves on electrocardiogram, electrocardiogram changes indicative of ischemia, or coronary artery intervention; (2) pathologic findings of AMI; or (3) ST elevation myocardial infarction (STEMI).  Pulmonary Embolism: (1) a positive ventilation-perfusion (V/Q) scan (2) a positive pulmonary angiography, or (3) a positive spiral (helical) CT scanning with intravenous contrast.  Study Groups: Patients were classified into two groups, based on the presence [CAP-FLU (+)] or absence [CAP-FLU (-)] of influenza. Statistical Analysis: Fisher’s Exact test was used to compare rates of cardiovascular events in the two study groups.  Another hypothesis that can explain CVEs in patients with pneumonia is the cardiovascular stress produce by the hypoxemia associated with pneumonia and the tachycardia associated with systemic infection.  The hypercoaguable state associated with sepsis may also play a role in the development of ischemia with the subsequent development of cardiovascular events.  Our data indicate that in patients with pneumonia due to influenza, the primary driver of cardiovascular events is the inflammation due to pneumonia. Background: Cardiovascular diseases, influenza, and pneumonia are leading causes of morbidity and mortality worldwide. Cardiovascular events (CVE) are common during the clinical course of pneumonia. Investigators have documented an increased incidence of cardiovascular events and associated mortality during the influenza season as well. However it is unknown as to if these associations are due to all-cause pneumonia or influenza-specific pneumonia. The objective of this study was to compare the incidence of cardiovascular events in patients with pneumonia due to influenza or pneumonia due to other etiologies. Methods: This was a secondary analysis of the RETOS database. Hospitalized patients with community-acquired pneumonia (CAP) were included in the analysis. Influenza was identified via PCR. Patients were classified into two groups, based on the presence [CAP-Flu (+)] or absence [CAP-Flu (-)] of influenza. Fisher’s Exact test was used to compare cardiovascular events. Results: A total of 800 patients with CAP were included in the study. Of the 112 CAP-Flu (+) patients, 14 (13%) had a CVE, while of the 688 CAP-Flu (-) patients, 77(11%) had a CVE (p=0.75). New serious arrhythmia and acute worsening of a long-term arrhythmia combined were the most frequent CVE in both groups [9% CAP-Flu (+) vs. 5% CAP-Flu (-)]. Conclusion: This study indicates that the incidence of CVEs in hospitalized patients with CAP is not affected by the presence of influenza; and also suggests that in pneumonia due to influenza the primary driver of CVEs is the inflammation due to pneumonia, not influenza by itself. ABSTRACT  A total of 800 patients with CAP were included in the study  CAP due to influenza [CAP-FLU(+)] was identified in 112 patients. CAP not due to influenza was identified in 688 patients ]CAP-FLU(-)]  The percentage of each of the cardiovascular events present in each study group is depicted in Figure 1  The number of patients enrolled in each study group and the percentage of cardiovascular events present in each study group are depicted in Figure 2 Figure 1: Percentage of each of the cardiovascular events present in each study group. Figure 2. Number of patients enrolled in each study group and the percentage of cardiovascular events present in each study group. MATERIALS AND METHODS RESULTS  Of the 112 CAP-FLU(+) patients, 14 (13%) had a CVE, while of the 688 CAP-FLU (-) patients, 77 (11%) had a CVE (p=0.75).  New serious arrhythmia and acute worsening of a long-term arrhythmia combined were the most frequent CVE in both groups [9% CAP-FLU (+) vs. 5% CAP-FLU (-)].  This study indicates that the incidence of CVEs in hospitalized patients with CAP is not affected by the presence of influenza.  Investigators have hypothesized that the increased risk of CVEs in this population is due to atherosclerotic plaque instability related to the systemic inflammation from pneumonia. CONCLUSIONS cont’d CONCLUSIONS REFERENCES