Time Is MuscleAcknowledgmentsREFERENCESTime Is MuscleTranslation Into PracticeElliott M. Antman, MD, FACCBoston, MassachusettsIn the future, advances in the care of patients with ST-segment elevation myocardial infarction (STEMI) will notcome from the analysis of trials that do not reflect current practice in an effort to rationalize extending the per-cutaneous coronary intervention (PCI)-related delay time. We must move beyond such arguments and find waysto shorten total ischemic time. With the launching of the American College of Cardiology’s D2B Alliance and theAmerican Heart Association’s Mission: Lifeline programs, the focus is now on systems improvement for reperfu-sion in patients with STEMI. The D2B Alliance was developed to focus on improvement in door-to-balloon timesfor patients with STEMI who are undergoing primary PCI. The American Heart Association Mission: Lifeline pro-gram is a broad, comprehensive national initiative to improve the quality of care and outcomes of patients withSTEMI by improving health care system readiness and response to STEMI. Improvements in access to timelycare for patients with STEMI will require a multifaceted approach involving patient education, improvements inthe Emergency Medical Services and emergency department components of care, the establishment of net-works of STEMI-referral hospitals (not PCI capable) and STEMI-receiving hospitals (PCI capable), as well as coor-dinated advocacy efforts to work with payers and policy makers to implement a much-needed health care sys-tem redesign. By focusing now on system efforts for improvements in timely care for STEMI, we will completethe cycle of research initiated by Reimer and Jennings 30 years ago. Time is muscle . . . we must translate thatinto practice. (J Am Coll Cardiol 2008;52:1216–21) © 2008 by the American College of Cardiology FoundationGiven the urgency of reperfusion of the occluded infarctartery in patients with ST-segment elevation myocardialinfarction (STEMI), it is not unexpected that the mostfrequently discussed aspects of management are the selec-tion and implementation of a reperfusion strategy. Despitethe importance of these topics, when attempting to writeguidelines for management of STEMI, clinicians shouldrealize that the “evidence” on which to base such recom-mendations is derived from databases that do not com-pletely answer all of our questions.For example, a frequently quoted overview by Keeleyet al. (1) in which they compare fibrinolytic reperfusion withcatheter-based reperfusion summarizes the experience froma total of only 7,739 patients enrolled collectively in 23randomized trials. These 23 trials have publication datesranging from 1990 to 2002, raising questions about theircontemporary relevance because of shifts in the use of othereffective therapies besides the exact mode of reperfusion forSTEMI.Furthermore, the largest difference in absolute event ratesbetween pharmacologic and catheter-based reperfusion wasin recurrent infarction (something that is difficult to diag-nose accurately in the setting of primary percutaneouscoronary intervention [PCI] for STEMI); the differences inmortality and hemorrhagic stroke, although still favoringthose patients undergoing primary PCI, were much moremodest. Contemporary attempts by researchers to merge the2 reperfusion strategies in the form of facilitated PCI (apreparatory pharmacologic regimen followed at varyingtimes by PCI) have not shown this approach to be anattractive one—there is no clear reduction in mortality orreinfarction with facilitated PCI, and concerns exist about adefinite increase in the risk of bleeding (2– 4).Despite the deficiencies in the evidence base, it is gener-ally accepted that primary PCI is the preferred mode ofreperfusion, provided it can be delivered in a timely fashionby an experienced operator (⬎75 PCI procedures/year) andteam (at least 200 PCI procedures per year, including atleast 36 primary PCI procedures/year) (5). The issue centerson what is meant by a “timely fashion.” Because in virtuallyall cases there is an inherent delay in implementation of aprimary PCI strategy, many analyses have been performedto provide guidance on the acceptable delays to primaryPCI—the metric “door-to-balloon” (D2B) time arose andwas initially proposed to be 120 min.By 2004, several pieces of evidence had emerged that ledto a shortening of the recommended D2B time to 90 min.Concern arose that long delays to primary PCI run counterto the guiding principle that “time is muscle,” as shown byFrom the TIMI Study Group, Cardiovascular Division, Brigham and Women’sHospital, Boston, Massachusetts.Manuscript received June 4, 2008; revised manuscript received July 2, 2008,accepted July 11, 2008.Journal of the American College of Cardiology Vol. 52, No. 15, 2008© 2008 by the American College of Cardiology Foundation ISSN 0735-1097/08/$34.00Published by Elsevier Inc. doi:10.1016/j.jacc.2008.07.011Reimer and Jennings nearly 30 years ago (6). Investigatorsunderstood that the amount of myocardial salvage per unittime from the moment of coronary occlusion is not linearbut rather curvilinear with the maximum amount of salvagein the first few hours after the onset of infarction, with sharpreductions in the amount of salvage thereafter as each hourpasses (7).Thus, total ischemic time is of paramount importanceand often is overlooked in discussions about time to reper-fusion. The importance of total ischemic time holds trueregardless of whether reperfusion is attempted with afibrinolytic or by PCI (8,9). Clinical trials in Europe testingthe strategy of transfer of STEMI patients from communityhospitals to PCI centers (10,11) consistently showed lowermortality in the transfer patients but also showed that it waspossible to implement the PCI strategy within 90 min fromrandomization—giving birth to the recommendations in2004 on both sides of the Atlantic that the system goalshould be to perform primary PCI within 90 min of the firstmedical contact (preferably the Emergency Medical Services[EMS] team in patients who call 911 [EMS-to-balloon ⫽90 min], but D2B should comprise 90 min in those patientswhose first medical contact is the door of the hospital)(5,12).Several authors have argued that the benefits of primaryPCI compared with fibrinolytic therapy extend well beyondthe 90-min window noted previously (13). Claims havebeen published that the benefit of primary PCI is stillobserved even if