title: Impact of the Timing of Metoprolol Administration During STEMI on Infarct Size and Ventricular Function.
abstract: BACKGROUND
  Pre-reperfusion administration of intravenous (IV) metoprolol reduces infarct size in ST-segment elevation myocardial infarction (STEMI).
  
  
  OBJECTIVE
  This study sought to determine how this cardioprotective effect is influenced by the timing of metoprolol therapy having either a long or short metoprolol bolus-to-reperfusion interval.
  
  
  METHODS
  We performed a post hoc analysis of the METOCARD-CNIC (effect of METOprolol of CARDioproteCtioN during an acute myocardial InfarCtion) trial, which randomized anterior STEMI patients to IV metoprolol or control before mechanical reperfusion. Treated patients were divided into short- and long-interval groups, split by the median time from 15 mg metoprolol bolus to reperfusion. We also performed a controlled validation study in 51 pigs subjected to 45 min ischemia/reperfusion. Pigs were allocated to IV metoprolol with a long (-25 min) or short (-5 min) pre-perfusion interval, IV metoprolol post-reperfusion (+60 min), or IV vehicle. Cardiac magnetic resonance (CMR) was performed in the acute and chronic phases in both clinical and experimental settings.
  
  
  RESULTS
  For 218 patients (105 receiving IV metoprolol), the median time from 15 mg metoprolol bolus to reperfusion was 53 min. Compared with patients in the short-interval group, those with longer metoprolol exposure had smaller infarcts (22.9 g vs. 28.1 g; p = 0.06) and higher left ventricular ejection fraction (LVEF) (48.3% vs. 43.9%; p = 0.019) on day 5 CMR. These differences occurred despite total ischemic time being significantly longer in the long-interval group (214 min vs. 160 min; p < 0.001). There was no between-group difference in the time from symptom onset to metoprolol bolus. In the animal study, the long-interval group (IV metoprolol 25 min before reperfusion) had the smallest infarcts (day 7 CMR) and highest long-term LVEF (day 45 CMR).
  
  
  CONCLUSIONS
  In anterior STEMI patients undergoing primary angioplasty, the sooner IV metoprolol is administered in the course of infarction, the smaller the infarct and the higher the LVEF. These hypothesis-generating clinical data are supported by a dedicated experimental large animal study.
authors.affiliation: Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: García-Ruiz
authors.affiliation: Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Fernández-Jiménez
authors.affiliation: Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Clinic, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: García-Alvarez
authors.affiliation: Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Universitario Quirón, Universidad Europea de Madrid, & Clínica Ruber-Quirónsalud, Madrid, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Pizarro
authors.affiliation: Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Galán-Arriola
authors.affiliation: Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Universitario HM Montepríncipe-CIEC, Madrid, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Fernández-Friera
authors.affiliation: Servicio de Urgencia Médica de Madrid-SUMMA112, Madrid, Spain; Universidad Francisco de Vitoria, Madrid, Spain.
authors.forename: Alonso
authors.initials: A
authors.lastname: Mateos
authors.affiliation: Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Nuno-Ayala
authors.affiliation: Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Aguero
authors.affiliation: Philips Healthcare Iberia, Iberia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Sánchez-González
authors.affiliation: Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: García-Prieto
authors.affiliation: Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Universitario HM Montepríncipe-CIEC, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: López-Melgar
authors.affiliation: Servicio de Urgencia Médica de Madrid-SUMMA112, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Martínez-Tenorio
authors.affiliation: Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Gonzalo J
authors.initials: GJ
authors.lastname: López-Martín
authors.affiliation: Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Macías
authors.affiliation: Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Braulio
authors.initials: B
authors.lastname: Pérez-Asenjo
authors.affiliation: Hospital Universitario Quirón, Universidad Europea de Madrid, & Clínica Ruber-Quirónsalud, Madrid, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Cabrera
authors.affiliation: Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernández-Ortiz
authors.affiliation: Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Valentín
authors.initials: V
authors.lastname: Fuster
authors.affiliation: Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Instituto de Investigación Sanitaria & Department of Cardiology, Fundación Jiménez Díaz Hospital, Madrid, Spain. Electronic address: bibanez@cnic.es.
authors.forename: Borja
authors.initials: B
authors.lastname: Ibáñez
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000008:administration & dosage*; D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004632:Emergency Medical Services; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage*; D008875:Middle Aged; D015425:Myocardial Reperfusion; D062645:Percutaneous Coronary Intervention; D000072657:ST Elevation Myocardial Infarction / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D013318:Stroke Volume / Q000187:drug effects*; D013552:Swine; D061665:Time-to-Treatment; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D008790:Metoprolol
keywords: cardiac magnetic resonance; cardioprotection; left ventricular ejection fraction; myocardial infarction; reperfusion injury