Effect of Early Metoprolol During ST-Segment Elevation Myocardial Infarction on Left Ventricular Strain: Feature-Tracking Cardiovascular Magnetic Resonance Substudy From the METOCARD-CNIC Trial.

This study sought to evaluate the effect of early intravenous metoprolol on left ventricular (LV) strain assessed with feature-tracking cardiovascular magnetic resonance (CMR). Early intravenous metoprolol before primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) portends better outcomes in the METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial. A total of 197 patients with acute anterior STEMI who were enrolled in the METOCARD-CNIC trial (100 allocated to intravenous metoprolol before primary PCI and 97 control patients) were evaluated. LV global circumferential strain (GCS) and global longitudinal strain (GLS) were measured with feature-tracking CMR at 1 week and 6 months after STEMI and compared between randomization groups. Patients who received early intravenous metoprolol had significantly more preserved LV strain compared with the control patients at 1 week after STEMI (GCS -13.9 ± 3.8% vs. -12.6 ± 3.9%, respectively; p = 0.013; GLS -11.9 ± 2.8% vs. -10.9 ± 3.2%, respectively; p = 0.032). In both groups, LV strain significantly improved during follow-up (mean difference between 6-month and 1-week strain for the metoprolol group: GCS -2.9%, 95% confidence interval [CI]: -3.5% to -2.4%; GLS: -2.9%, 95% CI: -3.4% to -2.4%; both p < 0.001; the control group: GCS -3.4%, 95% CI: -3.9% to -2.8%; GLS -3.4%, 95% CI: -3.9% to -3.0%; both p < 0.001). When dividing the overall cohort of patients in quartiles of GCS and GLS, there were significantly fewer patients in the first quartile (i.e., the worst LV systolic function) who received early intravenous metoprolol compared with control patients at 1 week and 6 months (p < 0.05 for GCS and GLS at both time points). In patients with anterior STEMI, early administration of intravenous metoprolol before primary PCI was associated with significantly fewer patients with severely depressed LV GCS and GLS, both at 1 week and 6 months. Feature-tracking CMR represents a complementary tool to evaluate the benefits of cardioprotective therapies. (Effect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion [METOCARD-CNIC]: NCT01311700).

Podlesnikar T ，Pizarro G ，Fernández-Jiménez R ，Montero-Cabezas JM ，Sánchez-González J ，Bucciarelli-Ducci C ，Ajmone Marsan N ，Fras Z ，Bax JJ ，Fuster V ，Ibáñez B ，Delgado V ... -  《-》

Left ventricular functional recovery of infarcted and remote myocardium after ST-segment elevation myocardial infarction (METOCARD-CNIC randomized clinical trial substudy).

Podlesnikar T ，Pizarro G ，Fernández-Jiménez R ，Montero-Cabezas JM ，Greif N ，Sánchez-González J ，Bucciarelli-Ducci C ，Marsan NA ，Fras Z ，Bax JJ ，Fuster V ，Ibáñez B ，Delgado V ... -  《-》

Five-Year Outcomes and Prognostic Value of Feature-Tracking Cardiovascular Magnetic Resonance in Patients Receiving Early Prereperfusion Metoprolol in Acute Myocardial Infarction.

The aim of the present study was to investigate the long-term impact of early intravenous metoprolol in ST-segment elevation myocardial infarction (STEMI) patients in terms of left ventricular (LV) strain with feature-tracking cardiovascular magnetic resonance (CMR) and its association with prognosis. A total of 270 patients with first anterior STEMI enrolled in the randomized METOCARD-CNIC clinical trial, assigned to receive up to 15 mg intravenous metoprolol before primary percutaneous coronary intervention versus conventional STEMI therapy, were included. LV global circumferential (GCS) and longitudinal (GLS) strain were assessed with feature-tracking CMR at 1 week after STEMI in 215 patients. The occurrence of major adverse cardiac events (MACE) at 5-year follow-up was the primary end point. Among 270 patients enrolled, 17 of 139 patients assigned to metoprolol arm and 31 of 131 patients assigned to control arm experienced MACE (hazard ratio [HR] 0.500, 95% confidence interval [CI] 0.277 to 0.903; p = 0.022). Impaired LV GCS and GLS strain were significantly associated with increased occurrence of MACE (GCS: HR 1.208, 95% CI 1.076 to 1.356, p =0.001; GLS: HR 1.362, 95% CI 1.180 to 1.573, p < 0.001). On multivariable analysis, LV GLS provided incremental prognostic value over late gadolinium enhancement (LGE) and LV ejection fraction (LVEF) (LGE + LVEF chi-square = 12.865, LGE + LVEF + GLS chi-square = 18.459; p =0.012). Patients with GLS ≥-11.5% (above median value) who received early intravenous metoprolol were 64% less likely to experience MACE than their counterparts with same degree of GLS impairment (HR 0.356, 95% CI 0.129 to 0.979; p = 0.045). In conclusion, early intravenous metoprolol has a long-term beneficial prognostic effect, particularly in patients with severely impaired LV systolic function. LV GLS with feature-tracking CMR early after percutaneous coronary intervention offers incremental prognostic value over conventional CMR parameters in risk stratification of STEMI patients.

Podlesnikar T ，Pizarro G ，Fernández-Jiménez R ，Montero-Cabezas JM ，Sánchez-González J ，Bucciarelli-Ducci C ，Ajmone Marsan N ，Fras Z ，Bax JJ ，Fuster V ，Ibáñez B ，Delgado V ... -  《-》

Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: results from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction).

The goal of this trial was to study the long-term effects of intravenous (IV) metoprolol administration before reperfusion on left ventricular (LV) function and clinical events. Early IV metoprolol during ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size when used in conjunction with primary percutaneous coronary intervention (pPCI). The METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial recruited 270 patients with Killip class ≤II anterior STEMI presenting early after symptom onset (<6 h) and randomized them to pre-reperfusion IV metoprolol or control group. Long-term magnetic resonance imaging (MRI) was performed on 202 patients (101 per group) 6 months after STEMI. Patients had a minimal 12-month clinical follow-up. Left ventricular ejection fraction (LVEF) at the 6 months MRI was higher after IV metoprolol (48.7 ± 9.9% vs. 45.0 ± 11.7% in control subjects; adjusted treatment effect 3.49%; 95% confidence interval [CI]: 0.44% to 6.55%; p = 0.025). The occurrence of severely depressed LVEF (≤35%) at 6 months was significantly lower in patients treated with IV metoprolol (11% vs. 27%, p = 0.006). The proportion of patients fulfilling Class I indications for an implantable cardioverter-defibrillator (ICD) was significantly lower in the IV metoprolol group (7% vs. 20%, p = 0.012). At a median follow-up of 2 years, occurrence of the pre-specified composite of death, heart failure admission, reinfarction, and malignant arrhythmias was 10.8% in the IV metoprolol group versus 18.3% in the control group, adjusted hazard ratio (HR): 0.55; 95% CI: 0.26 to 1.04; p = 0.065. Heart failure admission was significantly lower in the IV metoprolol group (HR: 0.32; 95% CI: 0.015 to 0.95; p = 0.046). In patients with anterior Killip class ≤II STEMI undergoing pPCI, early IV metoprolol before reperfusion resulted in higher long-term LVEF, reduced incidence of severe LV systolic dysfunction and ICD indications, and fewer heart failure admissions. (Effect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion. The METOCARD-CNIC Trial; NCT01311700).

Pizarro G ，Fernández-Friera L ，Fuster V ，Fernández-Jiménez R ，García-Ruiz JM ，García-Álvarez A ，Mateos A ，Barreiro MV ，Escalera N ，Rodriguez MD ，de Miguel A ，García-Lunar I ，Parra-Fuertes JJ ，Sánchez-González J ，Pardillos L ，Nieto B ，Jiménez A ，Abejón R ，Bastante T ，Martínez de Vega V ，Cabrera JA ，López-Melgar B ，Guzman G ，García-Prieto J ，Mirelis JG ，Zamorano JL ，Albarrán A ，Goicolea J ，Escaned J ，Pocock S ，Iñiguez A ，Fernández-Ortiz A ，Sánchez-Brunete V ，Macaya C ，Ibanez B ... -  《-》

Study design for the "effect of METOprolol in CARDioproteCtioN during an acute myocardial InfarCtion" (METOCARD-CNIC): a randomized, controlled parallel-group, observer-blinded clinical trial of early pre-reperfusion metoprolol administration in ST-segmen

Infarct size predicts post-infarction mortality. Oral β-blockade within 24 hours of a ST-segment elevation acute myocardial infarction (STEMI) is a class-IA indication, however early intravenous (IV) β-blockers initiation is not encouraged. In recent magnetic resonance imaging (MRI)-based experimental studies, the β(1)-blocker metoprolol has been shown to reduce infarct size only when administered before coronary reperfusion. To date, there is not a single trial comparing the pre- vs. post-reperfusion β-blocker initiation in STEMI. The METOCARD-CNIC trial is testing whether the early initiation of IV metoprolol before primary percutaneous coronary intervention (pPCI) could reduce infarct size and improve outcomes when compared to oral post-pPCI metoprolol initiation. The METOCARD-CNIC trial is a randomized parallel-group single-blind (to outcome evaluators) clinical effectiveness trial conducted in 5 Counties across Spain that will enroll 220 participants. Eligible are 18- to 80-year-old patients with anterior STEMI revascularized by pPCI ≤6 hours from symptom onset. Exclusion criteria are Killip-class ≥III, atrioventricular block or active treatment with β-blockers/bronchodilators. Primary end point is infarct size evaluated by MRI 5 to 7 days post-STEMI. Prespecified major secondary end points are salvage-index, left ventricular ejection fraction recovery (day 5-7 to 6 months), the composite of (death/malignant ventricular arrhythmias/reinfarction/admission due to heart failure), and myocardial perfusion. The METOCARD-CNIC trial is testing the hypothesis that the early initiation of IV metoprolol pre-reperfusion reduces infarct size in comparison to initiation of oral metoprolol post-reperfusion. Given the implications of infarct size reduction in STEMI, if positive, this trial might evidence that a refined use of an approved inexpensive drug can improve outcomes of patients with STEMI.

Ibanez B ，Fuster V ，Macaya C ，Sánchez-Brunete V ，Pizarro G ，López-Romero P ，Mateos A ，Jiménez-Borreguero J ，Fernández-Ortiz A ，Sanz G ，Fernández-Friera L ，Corral E ，Barreiro MV ，Ruiz-Mateos B ，Goicolea J ，Hernández-Antolín R ，Acebal C ，García-Rubira JC ，Albarrán A ，Zamorano JL ，Casado I ，Valenciano J ，Fernández-Vázquez F ，de la Torre JM ，Pérez de Prado A ，Iglesias-Vázquez JA ，Martínez-Tenorio P ，Iñiguez A ... -  《-》