Alonso Mateos

Effect of Early Metoprolol on Infarct Size in ST-Segment–Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention The Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) Trial

Background —The effect of β-blockers on infarct size when used in conjunction with primary percutaneous coronary intervention (PCI) is unknown. We hypothesize that metoprolol reduces infarct size when administered early (intravenously [i.v.] before reperfusion). Methods and Results —Patients with Killip-class ≤II anterior ST-segment elevation myocardial infarction (STEMI) undergoing PCI within 6 hours of symptoms onset were randomized to receive i.v. metoprolol (n=131) or not (control, n=139) pre-reperfusion. All patients without contraindications received oral metoprolol within 24 hours. The pre-defined primary endpoint was infarct size on magnetic resonance imaging (MRI) performed 5-7 days after STEMI. MRI was performed in 220 patients (81%). Mean (±SD) infarct size by MRI was smaller after i.v. metoprolol compared to control (25.6±15.3 vs. 32.0±22.2 grams; adjusted difference, -6.52; 95% confidence interval [CI], -11.39 to -1.78; P=0.012). In patients with pre-PCI TIMI flow grade 0/1, the adjusted treatment difference in infarct size was -8.02; 95% CI, -13.01 to -3.02; P=0.0029. Infarct size estimated by peak and area under the curve creatine-kinase release was measured in all study population and was significantly reduced by i.v. metoprolol. Left ventricular ejection fraction was higher in the i.v. metoprolol group (adjusted difference 2.67%; 95% CI, 0.09% to 5.21%; P=0.045). The composite of death, malignant ventricular arrhythmia, cardiogenic shock, atrioventricular block and reinfarction at 24 hours in the i.v. metoprolol and control groups respectively was 7.1% vs. 12.3%, p=0.21. Conclusions —In patients with anterior Killip-class ≤II STEMI undergoing primary PCI, early i.v. metoprolol before reperfusion reduced infarct size and increased LVEF with no excess of adverse events during the first 24 hours after STEMI. Clinical Trial Registration Information —ClinicalTrials.gov. Identifier: [NCT01311700][1] & EUDRACT Number 2010-019939-35. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01311700&atom=%2Fcirculationaha%2Fearly%2F2013%2F09%2F03%2FCIRCULATIONAHA.113.003653.atomBackground— The effect of &bgr;-blockers on infarct size when used in conjunction with primary percutaneous coronary intervention is unknown. We hypothesize that metoprolol reduces infarct size when administered early (intravenously before reperfusion). Methods and Results— Patients with Killip class II or less anterior ST-segment–elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention within 6 hours of symptoms onset were randomized to receive intravenous metoprolol (n=131) or not (control, n=139) before reperfusion. All patients without contraindications received oral metoprolol within 24 hours. The predefined primary end point was infarct size on magnetic resonance imaging performed 5 to 7 days after STEMI. Magnetic resonance imaging was performed in 220 patients (81%). Mean±SD infarct size by magnetic resonance imaging was smaller after intravenous metoprolol compared with control (25.6±15.3 versus 32.0±22.2 g; adjusted difference, −6.52; 95% confidence interval, −11.39 to −1.78; P=0.012). In patients with pre–percutaneous coronary intervention Thrombolysis in Myocardial Infarction grade 0 to 1 flow, the adjusted treatment difference in infarct size was −8.13 (95% confidence interval, −13.10 to −3.16; P=0.0024). Infarct size estimated by peak and area under the curve creatine kinase release was measured in all study populations and was significantly reduced by intravenous metoprolol. Left ventricular ejection fraction was higher in the intravenous metoprolol group (adjusted difference, 2.67%; 95% confidence interval, 0.09–5.21; P=0.045). The composite of death, malignant ventricular arrhythmia, cardiogenic shock, atrioventricular block, and reinfarction at 24 hours in the intravenous metoprolol and control groups was 7.1% and 12.3%, respectively (P=0.21). Conclusions— In patients with anterior Killip class II or less ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention, early intravenous metoprolol before reperfusion reduced infarct size and increased left ventricular ejection fraction with no excess of adverse events during the first 24 hours after STEMI. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01311700. EUDRACT number: 2010-019939-35.

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)

OBJECTIVES 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. BACKGROUND 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). METHODS 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. RESULTS 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). CONCLUSIONS 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).

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-segment elevation myocardial infarction

BACKGROUND 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. OBJECTIVE 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. DESIGN 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. CONCLUSIONS 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.

Efficacy and safety of out-of-hospital intravenous metoprolol administration in anterior ST-segment elevation acute myocardial infarction: insights from the METOCARD-CNIC trial.

STUDY OBJECTIVE We seek to examine the efficacy and safety of prereperfusion emergency medical services (EMS)-administered intravenous metoprolol in anterior ST-segment elevation myocardial infarction patients undergoing eventual primary angioplasty. METHODS This is a prespecified subgroup analysis of the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction trial population, who all eventually received oral metoprolol within 12 to 24 hours. We studied patients receiving intravenous metoprolol by EMS and compared them with others treated by EMS but not receiving intravenous metoprolol. Outcomes included infarct size and left ventricular ejection fraction on cardiac magnetic resonance imaging at 1 week, and safety by measuring the incidence of the predefined combined endpoint (composite of death, malignant ventricular arrhythmias, advanced atrioventricular block, cardiogenic shock, or reinfarction) within the first 24 hours. RESULTS From the total population of the trial (N=270), 147 patients (54%) were recruited during out-of-hospital assistance and transferred to the primary angioplasty center (74 intravenous metoprolol and 73 controls). Infarct size was smaller in patients receiving intravenous metoprolol compared with controls (23.4 [SD 15.0] versus 34.0 [SD 23.7] g; adjusted difference -11.4; 95% confidence interval [CI] -18.6 to -4.3). Left ventricular ejection fraction was higher in the intravenous metoprolol group (48.1% [SD 8.4%] versus 43.1% [SD 10.2%]; adjusted difference 5.0; 95% CI 1.6 to 8.4). Metoprolol administration did not increase the incidence of the prespecified safety combined endpoint: 6.8% versus 17.8% in controls (risk difference -11.1; 95% CI -21.5 to -0.6). CONCLUSION Out-of-hospital administration of intravenous metoprolol by EMS within 4.5 hours of symptom onset in our subjects reduced infarct size and improved left ventricular ejection fraction with no excess of adverse events during the first 24 hours.

Uncontrolled donation after circulatory death: European practices and recommendations for the development and optimization of an effective programme

The shortage of organs remains one of the biggest challenges in transplantation. To address this, we are increasingly turning to donation after circulatory death (DCD) donors and now in some countries to uncontrolled DCD donors. We consolidate the knowledge on uncontrolled DCD in Europe and provide recommendations and guidance for the development and optimization of effective uncontrolled DCD programmes.

Effect of Early Metoprolol on Infarct Size in ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary PCI: The METOCARD-CNIC Trial

Background —The effect of β-blockers on infarct size when used in conjunction with primary percutaneous coronary intervention (PCI) is unknown. We hypothesize that metoprolol reduces infarct size when administered early (intravenously [i.v.] before reperfusion). Methods and Results —Patients with Killip-class ≤II anterior ST-segment elevation myocardial infarction (STEMI) undergoing PCI within 6 hours of symptoms onset were randomized to receive i.v. metoprolol (n=131) or not (control, n=139) pre-reperfusion. All patients without contraindications received oral metoprolol within 24 hours. The pre-defined primary endpoint was infarct size on magnetic resonance imaging (MRI) performed 5-7 days after STEMI. MRI was performed in 220 patients (81%). Mean (±SD) infarct size by MRI was smaller after i.v. metoprolol compared to control (25.6±15.3 vs. 32.0±22.2 grams; adjusted difference, -6.52; 95% confidence interval [CI], -11.39 to -1.78; P=0.012). In patients with pre-PCI TIMI flow grade 0/1, the adjusted treatment difference in infarct size was -8.02; 95% CI, -13.01 to -3.02; P=0.0029. Infarct size estimated by peak and area under the curve creatine-kinase release was measured in all study population and was significantly reduced by i.v. metoprolol. Left ventricular ejection fraction was higher in the i.v. metoprolol group (adjusted difference 2.67%; 95% CI, 0.09% to 5.21%; P=0.045). The composite of death, malignant ventricular arrhythmia, cardiogenic shock, atrioventricular block and reinfarction at 24 hours in the i.v. metoprolol and control groups respectively was 7.1% vs. 12.3%, p=0.21. Conclusions —In patients with anterior Killip-class ≤II STEMI undergoing primary PCI, early i.v. metoprolol before reperfusion reduced infarct size and increased LVEF with no excess of adverse events during the first 24 hours after STEMI. Clinical Trial Registration Information —ClinicalTrials.gov. Identifier: [NCT01311700][1] & EUDRACT Number 2010-019939-35. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01311700&atom=%2Fcirculationaha%2Fearly%2F2013%2F09%2F03%2FCIRCULATIONAHA.113.003653.atomBackground— The effect of &bgr;-blockers on infarct size when used in conjunction with primary percutaneous coronary intervention is unknown. We hypothesize that metoprolol reduces infarct size when administered early (intravenously before reperfusion). Methods and Results— Patients with Killip class II or less anterior ST-segment–elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention within 6 hours of symptoms onset were randomized to receive intravenous metoprolol (n=131) or not (control, n=139) before reperfusion. All patients without contraindications received oral metoprolol within 24 hours. The predefined primary end point was infarct size on magnetic resonance imaging performed 5 to 7 days after STEMI. Magnetic resonance imaging was performed in 220 patients (81%). Mean±SD infarct size by magnetic resonance imaging was smaller after intravenous metoprolol compared with control (25.6±15.3 versus 32.0±22.2 g; adjusted difference, −6.52; 95% confidence interval, −11.39 to −1.78; P=0.012). In patients with pre–percutaneous coronary intervention Thrombolysis in Myocardial Infarction grade 0 to 1 flow, the adjusted treatment difference in infarct size was −8.13 (95% confidence interval, −13.10 to −3.16; P=0.0024). Infarct size estimated by peak and area under the curve creatine kinase release was measured in all study populations and was significantly reduced by intravenous metoprolol. Left ventricular ejection fraction was higher in the intravenous metoprolol group (adjusted difference, 2.67%; 95% confidence interval, 0.09–5.21; P=0.045). The composite of death, malignant ventricular arrhythmia, cardiogenic shock, atrioventricular block, and reinfarction at 24 hours in the intravenous metoprolol and control groups was 7.1% and 12.3%, respectively (P=0.21). Conclusions— In patients with anterior Killip class II or less ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention, early intravenous metoprolol before reperfusion reduced infarct size and increased left ventricular ejection fraction with no excess of adverse events during the first 24 hours after STEMI. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01311700. EUDRACT number: 2010-019939-35.

QRS distortion in pre-reperfusion electrocardiogram is a bedside predictor of large myocardium at risk and infarct size (a METOCARD-CNIC trial substudy).

BACKGROUND QRS distortion is an electrocardiographic (ECG) sign of severe ongoing ischemia in the setting of ST-segment elevation acute myocardial infarction (STEMI). We sought to evaluate the association between the degree of QRS distortion and myocardium at risk and final infarct size, measured by cardiac magnetic resonance (CMR). METHODS A total of 174 patients with a first anterior STEMI reperfused by primary angioplasty were prospectively recruited. Pre-reperfusion ECG was used to divide the study population into three groups according to the absence of QRS distortion (D0) or its presence in a single lead (D1) or in 2 or more contiguous leads (D2+). Myocardium at risk and infarct size were determined by CMR one week after STEMI. Multiple regression analysis was used to study the association of QRS distortion with myocardium at risk and infarct size, with adjustment for relevant clinical and ECG variables. RESULTS 101 patients (58%) were in group D0, 30 (17%) in group D1, and 43 (25%) in group D2+. Compared with group D0, presence of QRS distortion (groups D2+ and D1) was associated with a significantly adjusted larger extent of myocardium at risk (group D2+: absolute increase 10.4%, 95% CI 6.1-14.8%, p<0.001; group D1: absolute increase 3.3%, 95% CI 1.3-7.9%, p=0.157) and larger infarct size (group D2+: absolute increase 10.1%, 95% CI 5.5-14.7%, p<0.001; group D1: absolute increase 4.9%, 95% CI 0.08-9.8%, p=0.046). CONCLUSIONS Distortion in the terminal portion of the QRS complex on pre-reperfusion ECG in two or more leads is independently associated with larger myocardium at risk and infarct size in the setting of primary angioplasty-reperfused anterior STEMI. QRS distortion in only one lead is independently associated with larger infarct size in this setting. Our findings suggest that QRS distortion analysis could be included in risk-stratification of patients presenting with anterior STEMI.

Prehospital activation of cardiac catheterization teams in ST-segment elevation myocardial infarction

INTRODUCTION AND OBJECTIVES Current clinical guidelines for ST-segment elevation myocardial infarction (STEMI) suggest prehospital activation of the cardiac catheterization team. In previous protocols in our center activation occurred once patients arrived at the hospital. In January 2011, we initiated a new primary angioplasty activation protocol from prehospital locations. Our objective was to quantify the influence of this change on reperfusion times. METHODS A total of 173 consecutive STEMI patients (n=73/100 before/after initiation of the new protocol), diagnosed in a prehospital setting within 12 hours of symptom onset, were analyzed. The time between the patients arrival at the hospital and beginning of the angioplasty procedure was termed the cath lab activation delay. RESULTS The new protocol resulted in a 37-min reduction in system delay (166 [132-235] min before vs. 129 [105-166] min after, p<0.001), mostly driven by a 64% reduction in cath lab activation delay (55 [0-79] min before vs. 20 [0-54] min after, p=0.001). This reduction was mainly observed outside working hours. The percentage of patients treated with a system delay ≤ 120 min increased from 14.5% before the new protocol to 41.8% afterwards (p=0.001). CONCLUSIONS Prehospital activation of the cardiac catheterization team resulted in earlier reperfusion of STEMI patients.

Mechanical CPR devices in donors after cardiac death

Denmark) blood gas analyzer is fast and reliable. The ABL-90 is light and portable and data can be automatically sent to the patient data management system or even the physician’s PDA. A study was carried out in order to investigate the feasibility of the unit in amobile emergency care unit. Materials and methods: The response towards g-forces and vibration had to be assessed before implementing the unit in the MECU. A dummy with the same dimensions and weight as the ABL-90 was constructed. An accelerometer was placed on top of the dummy, measuring g-forces during several regular ambulance runs. Furthermore, the shock response spectrum of the unit was calculated.Uponestablishing theextentof g-forces exertedandcalculating the shock response spectrum, further testing was carried out. Results: Although g-forces exerted were rather low (1.5–1.95g in all directions), initial findings demonstrated that the ABL-90was unstable. An inlet of the apparatus proved to be responsible for discontinuation within the calibration system. A re-designed cradle with added cushioning and a new inlet, designed to minimize the risk of a discontinued connection between the inlet and solution pack, enabled the ABL-90 to function. Conclusions: This study has shown that a slightly modified ABL-90 works in a MECU. As the apparatus has the potential for transmitting prehospital results to intra hospital patient datamanagement systems, this finding opens up for improved diagnostic and treatment possibilities, both prehospitally and in preparing emergency departments for patients before their arrival at the departments.

Response to Letter Regarding Article, “Effect of Early Metoprolol on Infarct Size in ST-Segment–Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention: The Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) Trial”

We appreciate the interest of and comments by Drs Argulian and Messerli on our recently published study.1 Defining inclusion and exclusion criteria, along with dose selection of the administered pharmacological therapy, is critical in the early stages of a clinical trial design. The scientific method strongly recommends performing a profound bibliographic research in this regard, and for this purpose, we carefully reviewed previously conducted trials on the use of β-blockers in the setting of ST-segment–elevation acute myocardial infarction, taking note of the strengths and weaknesses of each of them. Thus, for the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) trial, we randomized anterior myocardial infarctions revascularized by primary angioplasty in <6 hours from symptom onset because this is the population that most benefits from any cardioprotective intervention. More important, and for safety reasons, we designed a trial to recruit patients with no obvious contraindications for the administration of intravenous metoprolol. Because β-blockers are clearly contraindicated in the acute phase …