How Long Is Too Long?
Objectives: The purpose of this study was to quantify the effect of time delays to reperfusion on ventricular function after myocardial infarction. This allows one to identify a group of patients in whom a strategy using antecedent pharmacologic reperfusion therapy before planned direct angioplasty may offer significant benefit.
Background: Direct angioplasty for myocardial infarction is associated with a high rate of successful reperfusion compared with pharmacologic reperfusion. However, there is an inherent time delay to treatment with angioplasty compared with pharmacologic therapy. There currently are insufficient data to determine the consequences of incremental time delays to reperfusion on ventricular function.
Methods: We determined, by logistic regression analysis, the probability of observing a decrement in postmyocardial infarction ventricular function as a function of incremental time delays to reperfusion.
Results: Time delays of 30, 60, 90, or 120 minutes to reperfusion increased the likelihood of a worse ventricular function outcome by 1.1-, 1.3-, 1.5-, and 1.7-fold, respectively (P < .02). The upper 95% confidence limits around these odds ratios are as high as 1.3 or 2.7 for 30- and 120-minute delays, respectively. Time from symptom onset to patency remained a significant determinant of ventricular function after adjustment for clinical and procedural factors.
Conclusions: Delay in time to reperfusion, measured in minutes, results in significant loss of ventricular function after myocardial infarction. Interventional strategies designed for treatment of myocardial infarction when "door-to-balloon" time is expected to exceed 60 minutes should strongly consider incorporation of pharmacologic reperfusion therapy into the therapeutic paradigm.

Time from symptom onset to reperfusion therapy is an important independent determinant of survival in the setting of acute myocardial infarction (AMI). The inverse relationship between time to treatment and survival has been attributed to increased salvage of left ventricular muscle with early infarct artery recanalization, but a precise quantitative relationship between time to reperfusion, expressed as a continuous variable, and ventricular muscle salvage has not been readily demonstrated in the clinical setting.

Infarct-related artery reperfusion strategies include direct percutaneous transluminal coronary angioplasty (PTCA) with or without intracoronary stent placement and stand-alone thrombolytic drug therapy. Direct PTCA is associated with a high success rate (74%-93%) (Thrombolysis In Myocardial Infarction [TIMI] 3) with regard to reestablishing normal flow. However, there is an inherent time delay from the time of patient arrival in the emergency department to balloon inflation, with median times approximating 2.0 to 2.5 hours. Thrombolytic therapy is readily available and may be given with minimum time delay. However, the success rate with currently available thrombolytic regimens approximates only 60%. The Plasminogen-activator Angioplasty Compatibility Trial (PACT) was designed to determine whether thrombolytic therapy administered before immediate planned coronary angiography and subsequent rescue angioplasty, if needed, would result in a greater degree of ventricular muscle salvage as determined by contrast ventriculography compared with direct angioplasty alone. Because there was no prespecified time for angiography in the PACT trial other than "as soon as possible" after the initial bolus injection of either tissue-type plasminogen activator (TPA) or placebo, the PACT database offered the unique opportunity to determine the effect of time delay to successful reperfusion, on a minute-to-minute basis, over a wide time range, on indices of convalescent left ventricular function.