title: Impact of left ventricular hypertrophy on troponin release during acute myocardial infarction: new insights from a comprehensive translational study.
abstract: BACKGROUND
  Biomarkers are frequently used to estimate infarct size (IS) as an endpoint in experimental and clinical studies. Here, we prospectively studied the impact of left ventricular (LV) hypertrophy (LVH) on biomarker release in clinical and experimental myocardial infarction (MI).
  
  
  RESULTS
  ST-segment elevation myocardial infarction (STEMI) patients (n=140) were monitored for total creatine kinase (CK) and cardiac troponin I (cTnI) over 72 hours postinfarction and were examined by cardiac magnetic resonance (CMR) at 1 week and 6 months postinfarction. MI was generated in pigs with induced LVH (n=10) and in sham-operated pigs (n=8), and serial total CK and cTnI measurements were performed and CMR scans conducted at 7 days postinfarction. Regression analysis was used to study the influence of LVH on total CK and cTnI release and IS estimated by CMR (gold standard). Receiver operating characteristic (ROC) curve analysis was performed to study the discriminatory capacity of the area under the curve (AUC) of cTnI and total CK in predicting LV dysfunction. Cardiomyocyte cTnI expression was quantified in myocardial sections from LVH and sham-operated pigs. In both the clinical and experimental studies, LVH was associated with significantly higher peak and AUC of cTnI, but not with differences in total CK. ROC curves showed that the discriminatory capacity of AUC of cTnI to predict LV dysfunction was significantly worse for patients with LVH. LVH did not affect the capacity of total CK to estimate IS or LV dysfunction. Immunofluorescence analysis revealed significantly higher cTnI content in hypertrophic cardiomyocytes.
  
  
  CONCLUSIONS
  Peak and AUC of cTnI both significantly overestimate IS in the presence of LVH, owing to the higher troponin content per cardiomyocyte. In the setting of LVH, cTnI release during STEMI poorly predicts postinfarction LV dysfunction. LV mass should be taken into consideration when IS or LV function are estimated by troponin release.
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (R.F.J., S.M.M., D.M., M.N.A., J.M.G.R., A.G., L.F.F., T.G.P., J.G.P., D.S.R., G.M., V.F., J.M.R., B.I.) Hospital Universitario Clínico San Carlos, Madrid, Spain (R.F.J., J.S., A.F.O., C.M., B.I.).
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Fernández-Jiménez
authors.affiliation: Hospital Universitario Clínico San Carlos, Madrid, Spain (R.F.J., J.S., A.F.O., C.M., B.I.).
authors.forename: Jacobo
authors.initials: J
authors.lastname: Silva
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (R.F.J., S.M.M., D.M., M.N.A., J.M.G.R., A.G., L.F.F., T.G.P., J.G.P., D.S.R., G.M., V.F., J.M.R., B.I.).
authors.forename: Sara
authors.initials: S
authors.lastname: Martínez-Martínez
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (R.F.J., S.M.M., D.M., M.N.A., J.M.G.R., A.G., L.F.F., T.G.P., J.G.P., D.S.R., G.M., V.F., J.M.R., B.I.).
authors.forename: M Dolores
authors.initials: MD
authors.lastname: López-Maderuelo
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (R.F.J., S.M.M., D.M., M.N.A., J.M.G.R., A.G., L.F.F., T.G.P., J.G.P., D.S.R., G.M., V.F., J.M.R., B.I.).
authors.forename: Mario
authors.initials: M
authors.lastname: Nuno-Ayala
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (R.F.J., S.M.M., D.M., M.N.A., J.M.G.R., A.G., L.F.F., T.G.P., J.G.P., D.S.R., G.M., V.F., J.M.R., B.I.) Hospital Universitario Central de Asturias, Oviedo, Spain (J.M.G.R.).
authors.forename: José Manuel
authors.initials: JM
authors.lastname: García-Ruiz
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (R.F.J., S.M.M., D.M., M.N.A., J.M.G.R., A.G., L.F.F., T.G.P., J.G.P., D.S.R., G.M., V.F., J.M.R., B.I.) Hospital Clinic, Barcelona, Spain (A.G.).
authors.forename: Ana
authors.initials: A
authors.lastname: García-Álvarez
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (R.F.J., S.M.M., D.M., M.N.A., J.M.G.R., A.G., L.F.F., T.G.P., J.G.P., D.S.R., G.M., V.F., J.M.R., B.I.) Hospital Universitario Montepríncipe, Madrid, Spain (L.F.F.).
authors.forename: Leticia
authors.initials: L
authors.lastname: Fernández-Friera
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (R.F.J., S.M.M., D.M., M.N.A., J.M.G.R., A.G., L.F.F., T.G.P., J.G.P., D.S.R., G.M., V.F., J.M.R., B.I.) Hospital Universitario Quirón Madrid UEM, Madrid, Spain (T.G.P.).
authors.forename: Tech Gonzalo
authors.initials: TG
authors.lastname: Pizarro
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (R.F.J., S.M.M., D.M., M.N.A., J.M.G.R., A.G., L.F.F., T.G.P., J.G.P., D.S.R., G.M., V.F., J.M.R., B.I.).
authors.forename: Jaime
authors.initials: J
authors.lastname: García-Prieto
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (R.F.J., S.M.M., D.M., M.N.A., J.M.G.R., A.G., L.F.F., T.G.P., J.G.P., D.S.R., G.M., V.F., J.M.R., B.I.).
authors.forename: David
authors.initials: D
authors.lastname: Sanz-Rosa
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (R.F.J., S.M.M., D.M., M.N.A., J.M.G.R., A.G., L.F.F., T.G.P., J.G.P., D.S.R., G.M., V.F., J.M.R., B.I.).
authors.forename: Gonzalo
authors.initials: G
authors.lastname: López-Martin
authors.affiliation: Hospital Universitario Clínico San Carlos, Madrid, Spain (R.F.J., J.S., A.F.O., C.M., B.I.).
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernández-Ortiz
authors.affiliation: Hospital Universitario Clínico San Carlos, Madrid, Spain (R.F.J., J.S., A.F.O., C.M., B.I.).
authors.forename: Carlos
authors.initials: C
authors.lastname: Macaya
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (R.F.J., S.M.M., D.M., M.N.A., J.M.G.R., A.G., L.F.F., T.G.P., J.G.P., D.S.R., G.M., V.F., J.M.R., B.I.) The Zena and Michael A. Wiener CVI, Mount Sinai School of Medicine, New York, NY (V.F.).
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (R.F.J., S.M.M., D.M., M.N.A., J.M.G.R., A.G., L.F.F., T.G.P., J.G.P., D.S.R., G.M., V.F., J.M.R., B.I.).
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Redondo
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (R.F.J., S.M.M., D.M., M.N.A., J.M.G.R., A.G., L.F.F., T.G.P., J.G.P., D.S.R., G.M., V.F., J.M.R., B.I.) Hospital Universitario Clínico San Carlos, Madrid, Spain (R.F.J., J.S., A.F.O., C.M., B.I.).
authors.forename: Borja
authors.initials: B
authors.lastname: Ibanez
mesh_terms: D000368:Aged; D000818:Animals; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D052279:Creatine Kinase, MB Form / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D004562:Electrocardiography / Q000379:methods; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood* / Q000175:diagnosis; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D012044:Regression Analysis; D012720:Severity of Illness Index; D034421:Sus scrofa; D013552:Swine; D057170:Translational Research, Biomedical / Q000379:methods*; D019210:Troponin I / Q000097:blood / Q000378:metabolism*; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; D019210:Troponin I; D052279:Creatine Kinase, MB Form
keywords: creatine kinase; hypertrophy; magnetic resonance imaging; myocardial infarction; troponin