Long-Term Benefit of Early Pre-Reperfusion Metoprolol Administration in Patients With Acute Myocardial Infarction

Pizarro, Gonzalo; Fernández‐Friera, Leticia; Fuster, Valentín; Fernández‐Jiménez, Rodrigo; García-Ruiz, José M.; García‐Álvarez, Ana; Mateos, Alonso; Barreiro, María V.; Escalera, Noemí; Rodríguez, María Susana; Miguel, Antonio De; García‐Lunar, Inés; Parra-Fuertes, Juan J.; Sánchez‐González, Javier; Pardillos, Luis; Nieto, Beatriz; Jiménez, A.E. Rodríguez; Abejón, Raquel; Bastante, Teresa; Vega, Vicente Martínez de; Cabrera, José Ángel; López-Melgar, Beatriz; Guzmán, Gabriela; García‐Prieto, Jaime; Mirelis, J. González; Zamorano, José Luís; Albarrán, Agustín; Goicolea, Javier; Escaned, Javier; Pocock, Stuart J.; Íñiguez, Andrés; Fernández‐Ortíz, Antonio; Sánchez-Brunete, Vicente; Macaya, Carlos; Ibáñez, Borja

doi:10.1016/j.jacc.2014.03.014

Cited by 157 publications

(32 citation statements)

References 29 publications

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“…In this trial, early i.v. metoprolol administration during ongoing AMI resulted in a significant reduction of infarct size939, and also significantly reduced the incidence of severe ventricular dysfunction and heart failure readmissions10. Large animal studies conducted before the METOCARD-CNIC trial showed that metoprolol reduces infarct size only when administered before reperfusion4041, suggesting that metoprolol might reduce infarct size by inhibiting reperfusion injury.…”

Section: Discussionmentioning

confidence: 99%

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Neutrophil stunning by metoprolol reduces infarct size

et al. 2017

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The β1-adrenergic-receptor (ADRB1) antagonist metoprolol reduces infarct size in acute myocardial infarction (AMI) patients. The prevailing view has been that metoprolol acts mainly on cardiomyocytes. Here, we demonstrate that metoprolol reduces reperfusion injury by targeting the haematopoietic compartment. Metoprolol inhibits neutrophil migration in an ADRB1-dependent manner. Metoprolol acts during early phases of neutrophil recruitment by impairing structural and functional rearrangements needed for productive engagement of circulating platelets, resulting in erratic intravascular dynamics and blunted inflammation. Depletion of neutrophils, ablation of Adrb1 in haematopoietic cells, or blockade of PSGL-1, the receptor involved in neutrophil–platelet interactions, fully abrogated metoprolol's infarct-limiting effects. The association between neutrophil count and microvascular obstruction is abolished in metoprolol-treated AMI patients. Metoprolol inhibits neutrophil–platelet interactions in AMI patients by targeting neutrophils. Identification of the relevant role of ADRB1 in haematopoietic cells during acute injury and the protective role upon its modulation offers potential for developing new therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

“…administration of the selective β1-adrenergic receptor (ADRB1) antagonist metoprolol has been shown to reduce infarct size and improve long-term cardiac function after AMI in the recent METOCARD-CNIC trial910. The mechanism underlying metoprolol's cardioprotective effect remains unclear11.…”

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confidence: 99%

Neutrophil stunning by metoprolol reduces infarct size

et al. 2017

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“…13–14 A prespecified analysis within this trial was the study of the association between cTnI/total CK and CMR‐measured LVH, IS, and LVEF. Inclusion/exclusion criteria can be found elsewhere.…”

Section: Methodsmentioning

confidence: 99%

“…15 Serial cTnI and total CK measurements were taken in 140 patients, and data from these patients were used for the current analysis. All patients underwent CMR studies at 5 to 7 days (1 week) 13 and 6 months 14 after STEMI. This study was approved by the ethics committee, and patients signed informed consent.…”

Section: Methodsmentioning

confidence: 99%

Impact of Left Ventricular Hypertrophy on Troponin Release During Acute Myocardial Infarction: New Insights From a Comprehensive Translational Study

Fernández‐Jiménez

Silva

Martı́nez-Martı́nez

et al. 2015

JAHA

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BackgroundBiomarkers 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).Methods and ResultsST‐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.ConclusionsPeak 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.

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“…In the 270 anterior STEMI patient METOCARD-CNIC trial, intravenous metoprolol administered in the ambulance prior to PPCI reduced MI size prevented LV adverse remodelling, preserved LV systolic function, and lowered hospital re-admissions for heart failure. 123,124 Results are awaited from the EARLY BAMI trial, which has recently completed recruitment of 600 STEMI patients and which investigated the effect of IV metoprolol or placebo prior to PPCI on MI size by cardiac MRI. 125 However, this therapeutic approach may not be suitable for all STEMI, and those with heart failure, hypotensive, or presenting with AV block will not qualify for this therapy.…”

Section: Metoprololmentioning

confidence: 99%