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Intravenous metoprolol during ongoing STEMI ameliorates markers of ischemic injury: a METOCARD-CNIC trial electrocardiographic study

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Abstract

Besides its protective effect against neutrophil-mediated injury at reperfusion, intravenous (IV) metoprolol was recently shown to reduce the progression of ischemic injury in a pig model of ST-segment elevation myocardial infarction (STEMI). Here, we tested the hypothesis that IV metoprolol administration in humans with ongoing STEMI blunts the time‑dependent progression of ischemic injury assessed by serial electrocardiogram (ECG) evaluations before reperfusion. The METOCARD-CNIC trial randomized 270 anterior STEMI patients to IV metoprolol or control before reperfusion by percutaneous coronary intervention (PCI). In 139 patients (69 IV metoprolol, 70 controls), two ECGs were available (ECG-1 before randomization, ECG-2 pre-PCI). Between-group ECG differences were analyzed using univariate and multivariate regression models. No significant between-group differences were observed on ECG-1. On ECG-2, patients who received IV metoprolol had a narrower QRS than those in the control group (84 ms vs. 90 ms, p = 0.029), a lower prevalence of QRS distortion (10% vs. 26%, p = 0.017), and a lower sum of anterior and total ST-segment elevation (10.1 mm vs. 13.6 mm, p = 0.014 and 10.4 mm vs. 14.0 mm, p = 0.015, respectively). Adjusted analysis revealed similar results. Significant associations were observed between ECG-2 variables and cardiac magnetic resonance imaging measurements (extent of myocardial edema, infarct size, microvascular obstruction, and left-ventricular ejection fraction) after STEMI. In summary, IV metoprolol administration before reperfusion ameliorates ECG markers of myocardial ischemia in anterior STEMI patients. These data confirm that IV metoprolol is able to reduce ischemic injury and highlight the ability of ECG analysis to provide relevant real-time information on the effect of cardioprotective therapies before reperfusion.

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Acknowledgements

Data of the present manuscript have been presented as part of R.D-M doctoral thesis. Simon Bartlett provided English editing.

Funding

Spanish Ministry of Science and Innovation (MICINN) RETOS2019-107332RB-I00 to B.I. Instituto de Salud Carlos III (ISCIII) PI19/01704 to R.F-J. European Research Council ERC-CoG 819775-MATRIX to B.I. European Union Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement No 707642 to R.F-J. The METOCARD-CNIC trial was sponsored by the CNIC (Translational Grant 01-2009), the Spanish National Ministry of Health and Social Policy (EC10-042), and the Mutua Madrileña Foundation (AP8695-2011). This study forms part of a Master Research Agreement between the CNIC and Philips Healthcare. The CNIC is supported by the ISCIII, the MICINN, and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015–0505).

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Authors and Affiliations

  1. Translational Laboratory for Cardiovascular Imaging and Therapy, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3, 28029, Madrid, Spain

    Raquel Díaz-Munoz, Gonzalo Pizarro, Noemi Escalera, Valentin Fuster, Rodrigo Fernández-Jiménez & Borja Ibanez

  2. Hospital Universitario Virgen Macarena, Sevilla, Spain

    María José Valle-Caballero & Juan Carlos García-Rubira

  3. Philips Healthcare, Madrid, Spain

    Javier Sanchez-Gonzalez

  4. CIBER de Enfermedades CardioVasculares, Madrid, Spain

    Gonzalo Pizarro, Noemi Escalera, Rodrigo Fernández-Jiménez & Borja Ibanez

  5. Ruber Juan Bravo Quironsalud Hospital UEM, Madrid, Spain

    Gonzalo Pizarro

  6. Icahn School of Medicine At Mount Sinai, New York, NY, USA

    Valentin Fuster

  7. Department of Cardiology, Hospital Universitario Clínico San Carlos, Madrid, Spain

    Rodrigo Fernández-Jiménez

  8. Department of Cardiology, Instituto de Investigación Sanitaria, Fundación Jiménez Díaz, Madrid, Spain

    Borja Ibanez

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  1. Raquel Díaz-Munoz
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Correspondence to Rodrigo Fernández-Jiménez or Borja Ibanez.

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Javier Sanchez-González is a Philips employee. All other authors state that they have no conflict of interests to declare.

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Díaz-Munoz, R., Valle-Caballero, M.J., Sanchez-Gonzalez, J. et al. Intravenous metoprolol during ongoing STEMI ameliorates markers of ischemic injury: a METOCARD-CNIC trial electrocardiographic study. Basic Res Cardiol 116, 45 (2021). https://doi.org/10.1007/s00395-021-00884-6

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