Rebeca Lorca1, Marta Jiménez-Blanco2, José Manuel García-Ruiz3, Gonzalo Pizarro4, Rodrigo Fernández-Jiménez5, Ana García-Álvarez6, Leticia Fernández-Friera7, Manuel Lobo-González8, Valentín Fuster9, Xavier Rossello10, Borja Ibáñez11. 1. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Área Gestión del Corazón, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Asturias, Spain; Universidad de Oviedo, Oviedo, Asturias, Spain. 2. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Servicio de Cardiología, Hospital Universitario Ramón y Cajal, Madrid, Spain. 3. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Servicio de Cardiología, Hospital de Cabueñes, Gijón, Asturias, Spain; Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, CIBERCV, Madrid, Spain. 4. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, CIBERCV, Madrid, Spain; Servicio de Cardiología, Complejo Hospitalario Ruber Juan Bravo, Madrid, Spain. 5. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, CIBERCV, Madrid, Spain; Servicio de Cardiología, Hospital Clínico San Carlos, Madrid, Spain. 6. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, CIBERCV, Madrid, Spain; Servicio de Cardiología, Hospital Clínic de Barcelona, Barcelona, Spain. 7. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, CIBERCV, Madrid, Spain; Área de Cardiología, Hospital Universitario Montepríncipe, Madrid, Spain. 8. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. 9. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Cardiology Department, Icahn School of Medicine at Mount Sinai, New York, United States. 10. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, CIBERCV, Madrid, Spain; Servicio de Cardiología, Hospital Universitari Son Espases, Palma de Mallorca, Balearic Islands, Spain. 11. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, CIBERCV, Madrid, Spain; Servicio de Cardiología, IIS-Fundación Jiménez Díaz, Madrid, Spain. Electronic address: bibanez@cnic.es.
Abstract
INTRODUCTION AND OBJECTIVES: According to the wavefront phenomenon described in the late 1970s, myocardial infarction triggered by acute coronary occlusion progresses with increasing duration of ischemia as a transmural wavefront from the subendocardium toward the subepicardium. However, whether wavefront progression of necrosis also occurs laterally has been disputed. We aimed to assess the transmural and lateral spread of myocardial damage after acute myocardial infarction in humans and to evaluate the impact of metoprolol on these. METHODS: We assessed myocardial infarction in the transmural and lateral dimensions in a cohort of 220 acute ST-segment elevation myocardial infarction (STEMI) patients from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction). The patients underwent cardiac magnetic resonance imaging at 5 to 7 days and 6 months post-STEMI. RESULTS: On day 5 to 7 post-STEMI cardiac magnetic resonance, there was a strong linear correlation between the transmural and lateral extent of infarction (delayed gadolinium enhancement) (r=-0.88; P<.001). Six months after STEMI, myocardial scarring (delayed gadolinium enhancement) was significantly less extensive in the transmural and lateral dimensions, suggesting that infarct resorption occurs in both. Furthermore, progression in both directions occurred both in patients receiving metoprolol and control patients, implying that myocardial salvage occurs both in the transmural and the lateral direction. CONCLUSIONS: Our findings challenge the assumption that irreversible injury does not spread laterally. A "circumferential" or multidirectional wavefront would imply that cardioprotective therapies might produce meaningful salvage at lateral borders of the infarct. This trial was registered at ClinicalTrial.gov (Identifier: NCT01311700).
INTRODUCTION AND OBJECTIVES: According to the wavefront phenomenon described in the late 1970s, myocardial infarction triggered by acute coronary occlusion progresses with increasing duration of ischemia as a transmural wavefront from the subendocardium toward the subepicardium. However, whether wavefront progression of necrosis also occurs laterally has been disputed. We aimed to assess the transmural and lateral spread of myocardial damage after acute myocardial infarction in humans and to evaluate the impact of metoprolol on these. METHODS: We assessed myocardial infarction in the transmural and lateral dimensions in a cohort of 220 acute ST-segment elevation myocardial infarction (STEMI) patients from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction). The patients underwent cardiac magnetic resonance imaging at 5 to 7 days and 6 months post-STEMI. RESULTS: On day 5 to 7 post-STEMI cardiac magnetic resonance, there was a strong linear correlation between the transmural and lateral extent of infarction (delayed gadolinium enhancement) (r=-0.88; P<.001). Six months after STEMI, myocardial scarring (delayed gadolinium enhancement) was significantly less extensive in the transmural and lateral dimensions, suggesting that infarct resorption occurs in both. Furthermore, progression in both directions occurred both in patients receiving metoprolol and control patients, implying that myocardial salvage occurs both in the transmural and the lateral direction. CONCLUSIONS: Our findings challenge the assumption that irreversible injury does not spread laterally. A "circumferential" or multidirectional wavefront would imply that cardioprotective therapies might produce meaningful salvage at lateral borders of the infarct. This trial was registered at ClinicalTrial.gov (Identifier: NCT01311700).
Keywords:
Cardioprotección; Cardioprotection; Daño por isquemia/reperfusión; Infarto agudo de miocardio; Ischemia/reperfusion injury; Metoprolol; Myocardial infarction; Onda de progresión del infarto; Wavefront phenomenon