Pre-Hospital Electrocardiography by Emergency Medical Personnel

Transcription

1 Journal of the American College of Cardiology Vol. 60, No. 9, by the American College of Cardiology Foundation ISSN /$36.00 Published by Elsevier Inc. Acute Coronary Syndromes Pre-Hospital Electrocardiography by Emergency Medical Personnel Effects on Scene and Transport Times for Chest Pain and ST-Segment Elevation Myocardial Infarction Patients Mitul Patel, MD,* James V. Dunford, MD, Steve Aguilar, MD, Edward Castillo, PHD, MPH, Ekta Patel, BE, Roger Fisher, BS, Ginger Ochs, RN, Ehtisham Mahmud, MD* San Diego, California Objectives Background Methods Results Conclusions This study sought to measure the impact of pre-hospital (PH) electrocardiography (ECG) on scene-to-hospital time for patients with chest pain of cardiac origin and those with ST-segment elevation myocardial infarction (STEMI). Pre-hospital ECG decreases door-to balloon (D2B) time for STEMI patients. However, obtaining a PH ECG might prolong scene time. We investigated the impact of obtaining a PH ECG on both scene and transport times for patients with chest pain suspected of cardiac origin. City of San Diego Emergency Medical System runsheets of patients with chest pain from January 2003 to April 2008 were analyzed. The scene times and transport times were compared before (from January 2003 to December 2005) and after (from January 2006 to April 2008) implementation of the PH ECG. Among patients with a PH ECG, median scene times and transport times were compared in patients with and without STEMI. There were 21,742 patients evaluated for chest pain during the study period. Implementation of PH ECG resulted in minimal increases in median scene time (19 min, 10 s vs. 19 min, 28 s, p 0.002) and transport time (13 min, 16 s vs. 13 min, 28 s, p 0.007). However, compared with chest pain patients, in STEMI patients (n 303), shorter median scene time (17 min, 51 s vs. 19 min, 31 s, p 0.001), transport time (12 min, 34 s vs. 13 min, 31 s, p 0.006), and scene-to-hospital time was observed (30 min, 45 s vs. 33 min, 29 s, p 0.001). Obtaining a PH ECG for patients with chest pain minimally prolongs scene and transport times. Further, for STEMI patients, both scene times and transport times are actually reduced leading to a potential reduction in total ischemic time. (J Am Coll Cardiol 2012;60:806 11) 2012 by the American College of Cardiology Foundation Coronary heart disease remains the leading cause of mortality in the United States (1). A number of pharmacological options, advancements in interventional techniques, and improved systems of care have led to significantly improved outcomes for patients with acute myocardial infarction (2). Timely administration of a thrombolytic agent or angioplasty of the infarct-related artery significantly improves outcomes for patients presenting with an ST-segment elevation myocardial infarction (STEMI) (3 6). In addition, sophisticated pre-hospital (PH) emergency medical From the *Division of Cardiovascular Medicine, University of California San Diego, San Diego, California; Department of Emergency Medicine, University of California San Diego, San Diego, California; Rural/Metro Ambulance, San Diego, California; and the San Diego Fire-Rescue Department, San Diego, California. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received November 14, 2011; revised manuscript received March 12, 2012, accepted March 13, services (EMS) systems have evolved to optimize the transport of patients suspected of myocardial infarction to not only the closest, but also the most appropriately equipped treatment facilities (7). Prior studies have highlighted the important role paramedics have played in the PH identification of STEMI with early identification leading to lower door-to-drug (D2D) time, door-to-balloon (D2B) time, and mortality (8 10). In fact, the most recent See page 812 American College of Cardiology/American Heart Association guidelines suggested a Class 1 recommendation for each community to develop a process for PH identification of STEMI. These same guidelines also emphasize that the benchmark for D2B time should be as soon as possible rather than 90 min (11). In patients treated with percutaneous coronary intervention for STEMI, each 30 min of delay translates into a 7.5%

2 JACC Vol. 60, No. 9, 2012 August 28, 2012: Patel et al. Pre-Hospital Electrocardiography 807 increase in the relative risk of 1-year mortality (12). In addition, when considering in-hospital mortality, a review of the National Cardiovascular Data Registry in 2005 to 2006 showed that for STEMI patients, longer D2B times were associated with a higher adjusted risk of mortality in a continuous nonlinear fashion (30 min 3.0%, 60 min 3.5%, 90 min 4.3%, 120 min 5.6%, 150 min 7.0%, 180 min 8.4%; p 0.001) (13). Along these lines, multiple studies evaluating the use of a PH 12-lead electrocardiogram (ECG) have demonstrated the benefits of its implementation for decreasing overall D2D time and D2B time in patients with STEMI (10,14 24). In particular, 2 large, multicenter studies have demonstrated clinically relevant time savings, resulting in a 10-min decrease in D2D time and 15- to 20-min decreases in D2B time (16,17). Additionally, the successful achievement of D2B time 90 min was shown in 86% of STEMI cases when a PH ECG was used for cardiac triage in 10 STEMI receiving center networks across the United States (25). Currently, approximately 90% of EMS systems serving the 200 largest cities in the United States have PH 12-lead ECG capability (26). However, though the PH ECG helps in reducing the D2B time, some have suggested it may increase total ischemic time by prolonging the time obtaining an ECG at the scene and thus offsetting the reduction in D2B time (16,27 30). We undertook this study to measure the impact of obtaining a PH ECG on both the scene and transport times for out-of-hospital patients with chest pain suspected of cardiac origin. In addition, we sought to measure the impact of obtaining a PH ECG on scene and transport times for patients diagnosed with a STEMI. Methods This study analyzes a subset of patients managed by the San Diego Medical Services (SDMS), a public-private partnership between the San Diego Fire-Rescue Department and the Rural/Metro Corporation of San Diego. SDMS is the exclusive provider of paramedic services to the City of San Abbreviations and Acronyms D2B door to balloon D2D door to drug ECG electrocardiogram/ electrocardiography EMS emergency medical services PH pre-hospital SDMS San Diego Medical Services STEMI ST-segment elevation myocardial infarction Diego, the nation s eighth largest city, with a population of 1.3 million residing in a 342-squaremile land area. SDMS deploys 450 paramedics on 60 advanced life support first responder vehicles (fire engines and trucks) and 26 ambulances. Fire first responder units are deployed with 3 emergency medical technicians and 1 paramedic, and typically begin assessment (including PH ECG acquisition) and stabilization before ambulance arrival. The study protocol was approved by the Institutional Review Board of the University of California, San Diego. We retrospectively analyzed the City of San Diego computer-aided dispatch system and emergency medical system runsheets of patients with chest pain between January 2003 and December 2005 (period of time before the implementation of the PH ECG) and compared the data to the time period between January 2006 and April 2008 (after the implementation of the PH ECG). In this study, a STEMI was defined by the interpretation of the Marquette (General Electric, Waukesha, Wisconsin) software algorithm. The time from arrival of the first paramedic-staffed unit (fire first responder or ambulance) to departure of the ambulance was recorded as the scene time. The transport time was documented as the time from ambulance scene departure to the time of arrival at the emergency department. The scene-tohospital time was calculated as the time from arrival at the scene to the arrival at the emergency department (Fig. 1). For the primary analysis, the median scene time, transport time, and scene-to-hospital time were compared before and after implementation of the PH ECG for the entire chest pain cohort. A secondary analysis was restricted to the 9,631 after PH ECG implementation cohort and the same time intervals were compared between patients Figure 1 Chest Pain Protocol After Activation A schematic representation of the intervals comprising the scene time, transport time and scene to hospital time after activation for patients with chest pain suspected of cardiac origin. ECG electrocardiogram.

3 808 Patel et al. JACC Vol. 60, No. 9, 2012 Pre-Hospital Electrocardiography August 28, 2012: Scene, Before and Transport, After Scene, PH and Transport, ECG Scene-to-Hospital Implementation and Scene-to-Hospital Times Times Table 1 Before and After PH ECG Implementation Period n Median (Interquartile Range) p Value Scene time (min:s) Before PH ECG 12,111 19:10 (15:23 23:20) After PH ECG 9,631 19:28 (15:41 23:33) 0:14 Transport time (min:s) Before PH ECG 12,104 13:16 (9:27 17:42) After PH ECG 9,613 13:28 (9:51 17:51) 0:12 Scene-to-hospital time (min:s) Before PH ECG 12,098 33:04 (27:50 38:49) After PH ECG 9,611 33:25 (28:10 39:18) 0:21 ECG electrocardiogram; PH pre-hospital. with STEMI versus no STEMI using a Mann-Whitney U test. Medians, interquartile ranges, and associated p values are presented. Data were analyzed with SPSS version 16.0 (SPSS, Inc., Chicago, Illinois). Results There were 21,742 patients (mean age years; 53% male) evaluated by EMS activation for chest pain potentially of cardiac origin between January 2003 and April 2008 in the City of San Diego. Baseline demographic data are presented in Table 1. In total, 12,111 of these cases were before the implementation of the PH ECG (between January 2003 and December 2005; 35 months) and 9,631 were after (between January 2006 and April 2008; 27 months). Of the 12,111 cases before the institution of PH ECGs, all except 7 patients were transported and, of the 9,631 cases with PH ECGs, all except 18 patients were transported (Table 1). After institution of the PH ECG, 303 patients (3.1%) were diagnosed with a STEMI in the field (Table 2). Implementation of the PH ECG resulted in minimal increases in median scene time (19 min, 10 s vs. 19 min, 28 s, p 0.002) and transport time (13 min, 16 s vs. 13 min, 28 s, p 0.007) in the study cohort (Fig. 2). However, compared with chest pain patients, when PH ECG suggested a STEMI (n 303), significantly shorter median scene time (17 min, 51 s vs. 19 min, 31 s, p 0.001) and transport time (12 min, 34 s vs. 13 min, 31 s, p 0.006) were observed (Fig. 3). This shortened the median sceneto-hospital time by 2 min, 44 s (30 min, 45 s vs. 33 min, 29 s, p 0.001) for the study cohort with a PH ECG diagnosis of STEMI (Table 2, Fig. 3). Discussion This study demonstrates that the reduction in door-toreperfusion time with PH ECG is not at the expense of delays in obtaining the PH 12-lead ECG at the scene by EMS. Implementing a PH ECG adds trivial delay to the total time EMS personnel spend on patients with chest pain. These findings support the use of PH ECG for all EMS response patients experiencing chest pain. In particular, the clinically insignificant 18-s prolongation in scene time in our cohort is in contrast to previous reports demonstrating an average increase of 1.2 to 5.2 min in the on-scene time interval (21,27 29,32). This difference may be a reflection of our EMS system design, which deploys paramedics on both fire first responders and ambulances and thereby increases the efficiency of rapid patient assessment. Importantly, utilization of PH ECG did not result in delay of care for chest pain patients or specifically STEMI patients. Before the PH ECG, it has been posited that STEMI/ acute coronary syndrome patients transported by EMS could expect delay from time of symptom onset to reperfusion therapy. Potential delay has been divided into 4 time Scene, STEMI Versus Transport, Scene, No STEMI and Transport, Scene-to-Hospital Diagnosis and Scene-to-Hospital After Times PH ECG in Implementation Times in Table 2 STEMI Versus No STEMI Diagnosis After PH ECG Implementation Diagnosis n Median (Interquartile Range) p Value Scene time (min:s) No STEMI 9,328 19:31 (15:46 23:35) STEMI :51 (13:19 22:34) 1:40 Transport time (min:s) No STEMI 9,311 13:31 (9:52 17:53) STEMI :34 (9:15 16:36) 0:57 Scene-to-hospital time (min:s) No STEMI 9,309 33:29 (28:17 39:20) STEMI :45 (24:30 37:31) 2:44 STEMI ST-segment elevation myocardial infarction; other abbreviations as in Table 1.

4 JACC Vol. 60, No. 9, 2012 August 28, 2012: Patel et al. Pre-Hospital Electrocardiography 809 Figure 2 Impact of Obtaining a PH ECG on Emergency Medical System Time Scene time, transport time, and scene to hospital time (h:min:s) prior to (n 12,111), and after implementation of routine pre-hospital electrocardiogram (PH ECG) (n 9,631) for patients with chest pain suspected of cardiac origin. No clinically relevant delay was observed with routinely obtaining a PH ECG. Reported as median values with interquartile ranges (25th, 75th percentile). intervals: 1) symptom onset to EMS arrival; 2) EMS arrival to hospital arrival; 3) hospital arrival to ECG; and 4) ECG to reperfusion. With a PH ECG, the third interval can be eliminated and fourth time interval is shortened with advanced notification of the hospital, activation of the catheterization laboratory en route, and/or bypass of the emergency department to the catheterization laboratory (24,33 38). In this study, we address the second interval and demonstrate that EMS personnel have improved their workflow to insure that PH ECG does not adversely prolong both scene and transport times for patients who are evaluated for chest pain of potential cardiac origin. In fact, when the diagnosis of STEMI is made in the field, the EMS arrival-to-hospital time is lower than for other chest pain patients thereby potentially reducing total ischemic time. These findings suggest that previous reports of reduced ischemic time with PH ECG may have been underestimated, as the reduction in the D2D and D2B time intervals do not take into account the additional reduction in PH scene and transport times (10,14 17,19 23,31). For patients presenting with a STEMI in the City of San Diego, obtaining a PH ECG led to significantly lower median scene time, transport time, and overall scene-to-hospital time compared with chest pain patients without STEMI. The decrease of 1 min 40 s in the median scene time and 57 s in median transport time resulted in an overall reduction of 2 m in 44 s of pre-hospital ischemic time. These findings reflect additional reduction in total ischemic time when considering the reductions in D2B time achieved by field activation of the cardiac catheterization laboratory. Although it is clear in this study that patients identified by PH ECG with STEMI actually received expedited care, how EMS personnel achieved this efficiency is unknown. It is possible that once identified, obvious and suspected STEMI patients were treated with greater urgency resulting in expedited transport to the closest STEMI center. It is also possible that these patients might appear to be in greater extremis on the basis of a clinical evaluation and would have reduced scene and transport times independent of the ECG findings. Cities or counties that have instituted a PH ECG protocol and/or have developed appropriate STEMI triage networks have shown significant improvements in both D2B times and first medical contact to balloon times in smaller patient populations (25,39). The city and county of San Diego also established a PH ECG identification of STEMI with preferential transport to a percutaneous coronary intervention capable hospital in January This has the potential to confound the findings of this study. This study assumed that all patients with the chief complaint of chest pain of suspected cardiac origin received a 12-lead ECG because it was the protocol during the study period, and extensive paramedic training focused

5 810 Patel et al. JACC Vol. 60, No. 9, 2012 Pre-Hospital Electrocardiography August 28, 2012: Figure 3 PH ECG and Shorter Emergency Medical System Time for STEMI Patients Scene time, transport time, and scene to hospital time intervals in the no ST-segment elevation myocardial infarction (STEMI) (n 9,328) vs. STEMI patients (n 303) (h:min:s) after routine implementation of the pre-hospital electrocardiogram (PH ECG) for patients with chest pain suspected of cardiac origin. In STEMI patients routine PH ECG was associated with shorter scene to hospital time reflecting additional reduction in total ischemic time. Reported as median values with interquartile ranges (25th, 75th percentile). on this chief complaint as the primary criteria to perform an ECG. However, only PH ECGs that demonstrated a software interpretation of an acute STEMI were mandatorily saved and uploaded for review and storage. Nevertheless, this large population-based study supports the notion that obtaining a PH ECG does not prolong ischemic time in the setting of a STEMI, and might actually reduce it. We acknowledge that ideally a comparison of the various time intervals in the STEMI subgroup pre- and postimplementation of the PH ECG would further strengthen the presented data. However, before the implementation of the PH ECG in our community, specific identification of STEMI patients was not available. Conclusions Obtaining a PH ECG by emergency medical personnel for patients with chest pain suspected of cardiac origin adds trivial time at the scene and during transport to the hospital. Compared with all chest pain patients, for patients with a STEMI on a PH ECG, both of these time intervals are actually shorter and complement the benefits of previously established reductions in D2B times with a PH ECG. Acknowledgements The authors would like to thank San Diego Medical Services (the paramedic provider for the city) whose international award-winning electronic health record, Tapchart, allowed for ease in data acquisition. Reprint requests and correspondence: Dr. Ehtisham Mahmud, UC San Diego Sulpizio Cardiovascular Center, 9434 Medical Center Drive #7784, La Jolla, California emahmud@ucsd.edu. REFERENCES 1. Lloyd-Jones D, Adams R, Carnethon M, et al. Heart Disease and Stroke Statistics 2009 update. A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009;119:e Fox KA, Steg PG, Eagle KA, et al. Decline in rates of death and heart failure in acute coronary syndromes, JAMA 2007;297: The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329: Berger PB, Ellis SG, Holmes DR Jr., et al. Relationship between delay in performing direct coronary angioplasty and early clinical outcome in patients with acute myocardial infarction: results from the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb) trial. Circulation 1999;100: Cannon CP, Gibson CM, Lambrew CT, et al. Relationship of symptom-onset-to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acute myocardial infarction. JAMA 2000;283: McNamara RL, Wang Y, Herrin J, et al. Effect of door-to-balloon time on mortality in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol 2006;47:

6 JACC Vol. 60, No. 9, 2012 August 28, 2012: Patel et al. Pre-Hospital Electrocardiography Le May MR, So DY, Dionne R, et al. and others. A citywide protocol for primary PCI in ST-segment elevation myocardial infarction. N Engl J Med 2008;358: van t Hof AW, Rasoul S, van de Wetering H, et al. Feasibility and benefit of prehospital diagnosis, triage, and therapy by paramedics only in patients who are candidates for primary angioplasty for acute myocardial infarction. Am Heart J 2006;151:1255.e Le May MR, Dionne R, Maloney J, Poirier P. The role of paramedics in a primary PCI program for ST-elevation myocardial infarction. Prog Cardiovasc Dis 2010;53: Foster DB, Dufendach JH, Barkdoll CM, Mitchell BK. Prehospital recognition of AMI using independent nurse/paramedic 12-lead ECG evaluation: impact on in-hospital times to thrombolysis in a rural community hospital. Am J Emerg Med 1994;12: Kushner FG, Hand M, Smith SC Jr., et al focused updates: ACC/AHA guidelines for the management of patients with STelevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update): a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2009;54: De Luca G, Suryapranata H, Ottervanger JP, Antman EM. Time delay to treatment and mortality in primary angioplasty for acute myocardial infarction: every minute of delay counts. Circulation 2004;109: Rathore SS, Curtis JP, Chen J, et al., for the National Cardiovascular Data Registry. Association of door-to-balloon time and mortality in patients admitted to hospital with ST elevation myocardial infarction: national cohort study. BMJ 2009;338:b Brainard AH, Raynovich W, Tandberg D, Bedrick EJ. The prehospital 12-lead electrocardiogram s effect on time to initiation of reperfusion therapy: a systematic review and meta-analysis of existing literature. Am J Emerg Med 2005;23: Brown JP, Mahmud E, Dunford JV, Ben-Yehuda O. Effect of prehospital 12-lead electrocardiogram on activation of the cardiac catheterization laboratory and door-to-balloon time in ST-segment elevation acute myocardial infarction. Am J Cardiol 2008;101: Canto JG, Rogers WJ, Bowlby LJ, French WJ, Pearce DJ, Weaver WD. The prehospital electrocardiogram in acute myocardial infarction: is its full potential being realized? National Registry of Myocardial Infarction 2 Investigators. J Am Coll Cardiol 1997;29: Curtis JP, Portnay EL, Wang Y, et al. The pre-hospital electrocardiogram and time to reperfusion in patients with acute myocardial infarction, : findings from the National Registry of Myocardial Infarction-4. J Am Coll Cardiol 2006;47: Ferguson JD, Brady WJ, Perron AD, et al. The prehospital 12-lead electrocardiogram: impact on management of the out-of-hospital acute coronary syndrome patient. Am J Emerg Med 2003;21: Ioannidis JP, Salem D, Chew PW, Lau J. Accuracy and clinical effect of out-of-hospital electrocardiography in the diagnosis of acute cardiac ischemia: a meta-analysis. Ann Emerg Med 2001;37: Karagounis L, Ipsen SK, Jessop MR, et al. Impact of field-transmitted electrocardiography on time to in-hospital thrombolytic therapy in acute myocardial infarction. Am J Cardiol 1990;66: Morrison LJ, Brooks S, Sawadsky B, McDonald A, Verbeek PR. Prehospital 12-lead electrocardiography impact on acute myocardial infarction treatment times and mortality: a systematic review. Acad Emerg Med 2006;13: Myers RB. Prehospital management of acute myocardial infarction: Electrocardiogram acquisition and interpretation, and thrombolysis by prehospital care providers. Can J Cardiol 1998;14: Terkelsen CJ, Lassen JF, Norgaard BL, et al. Reduction of treatment delay in patients with ST-elevation myocardial infarction: impact of pre-hospital diagnosis and direct referral to primary percutanous coronary intervention. Eur Heart J 2005;26: Bradley EH, Herrin J, Wang Y, et al. Strategies for reducing the door-to-balloon time in acute myocardial infarction. N Engl J Med 2006;355: Rokos IC, French WJ, Koenig WJ, et al. Integration of pre-hospital electrocardiograms and ST-Elevation Myocardial Infarction Receiving Center (SRC) networks: impact on door-to-balloon times across 10 independent regions. J Am Coll Cardiol Intv 2009;2: Williams DM JEMS 200-city survey. EMS from all angles. JEMS 2007;32:38 42, 44, 46 passim. 27. Aufderheide TP, Hendley GE, Thakur RK, et al. The diagnostic impact of prehospital 12-lead electrocardiography. Ann Emerg Med 1990;19: Aufderheide TP, Hendley GE, Woo J, Lawrence S, Valley V, Teichman SL. A prospective evaluation of prehospital 12-lead ECG application in chest pain patients. J Electrocardiol 1992;24 Suppl: Aufderheide TP, Keelan MH, Hendley GE, et al. Milwaukee Prehospital Chest Pain Project phase I: feasibility and accuracy of prehospital thrombolytic candidate selection. Am J Cardiol 1992;69: Weaver WD, Eisenberg MS, Martin JS, et al. Myocardial Infarction Triage and Intervention Project phase I: patient characteristics and feasibility of prehospital initiation of thrombolytic therapy. J Am Coll Cardiol 1990;15: Ferguson JJ, Califf RM, Antman EM, et al. Enoxaparin vs unfractionated heparin in high-risk patients with non-st-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. JAMA 2004;292: Grim PS, Feldman T, Childers RW. Evaluation of patients for the need of thrombolytic therapy in the prehospital setting. Ann Emerg Med 1989;18: Bradley EH, Curry LA, Webster TR, et al. Achieving rapid door-toballoon times: how top hospitals improve complex clinical systems. Circulation 2006;113: Bradley EH, Roumanis SA, Radford MJ, et al. Achieving door-toballoon times that meet quality guidelines: how do successful hospitals do it? J Am Coll Cardiol 2005;46: Dhruva VN, Abdelhadi SI, Anis A, et al. ST-Segment Analysis Using Wireless Technology in Acute Myocardial Infarction (STAT-MI) trial. J Am Coll Cardiol 2007;50: Gross BW, Dauterman KW, Moran MG, et al. An approach to shorten time to infarct artery patency in patients with ST-segment elevation myocardial infarction. Am J Cardiol 2007;99: Nallamothu BK, Bradley EH, Krumholz HM. Time to treatment in primary percutaneous coronary intervention. N Engl J Med 2007;357: Swor R, Hegerberg S, McHugh-McNally A, Goldstein M, McEachin CC. Prehospital 12-lead ECG: efficacy or effectiveness? Prehosp Emerg Care 2006;10: Scholz KH, Hilgers R, Ahlersmann D, et al. Contact-to-balloon time and door-to-balloon time after initiation of a formalized data feedback in patients with acute ST-elevation myocardial infarction. Am J Cardiol 2008;101: Key Words: electrocardiography y ischemia y myocardial infarction y reperfusion.