Optimizing Reperfusion in Patients With STEMI
Optimizing Reperfusion in Patients With STEMI
The adage that 'time is tissue' holds true in most studies examining the association between delay to reperfusion and clinical outcomes. Conceptually, there is an early period of time-dependent mortality reduction within approximately 3 h from symptom onset where substantial myocardium can be salvaged with reperfusion. Based on the model developed by Gersh et al., after 6 h from symptom onset, the benefit of reperfusion therapy, while still present, becomes less time dependent and the mortality reduction versus time to reperfusion therapy slope becomes less acute. During this late period, the goal is to open the infarct-related artery, and D2B time is not as critical. Consequently, one would not want to select a reperfusion strategy that leads to a delay, shifting from a critically time-dependent phase to a less time-dependent phase of infarction, and decreasing the potential for myocardial salvage.
With this construct in mind, clinical studies have clearly demonstrated that longer D2B time delay is associated with increased mortality. A review of 29,222 patients in the National Registry of Myocardial Infarction (NRMI) 3 and 4 found that mortality is 3.0 % when D2B time is <90 min and 7.4 % when D2B time is >150 min. It has been demonstrated that several patient-related factors, such as female sex, age >70 years, diabetes mellitus, and prior PCI are associated with longer D2B time delay, likely due to atypical presentations, higher medical complexity, and more patient instability. Similar results linking D2B time to short-term and long-term mortality have been found in other clinical trials and registry analyses
Extensive efforts involving professional organizations, individual hospitals, and hospital networks have aimed to improve D2B time. For example, the American College of Cardiology (ACC) and its partners launched the D2B Alliance in 2006 as a national campaign to decrease D2B time. A study of D2B time in the National Cardiovascular Data Registry (NCDR) CathPCI registry showed that, in 2005, only 52.5 % of patients presenting to a PCI-capable hospital had D2B time <90 min compared with 76.4 % by 2008. A later study determined that even among patients with D2B time <90 min, a mortality benefit may exist in decreasing D2B time even further.Table 1 compares D2B time in various trials and registry analyses conducted over the last 2 decades.
Interestingly, symptom-to-balloon time, also known as total ischemic time, has had varying associations with morbidity and mortality in several analyses. A large Danish registry of >6,200 patients who underwent PPCI found that shorter symptom-to-balloon time was not associated with reduced mortality at 3 years, whereas there was an increase in mortality with longer FMC-to-balloon time. Similarly, among 27,000 patients from NRMI-2, there was no association between mortality and symptom-to-balloon time, but an increased mortality for D2B time >120 min was seen.
There are several reasons why an association between symptom-to-balloon time and mortality may be difficult to demonstrate. First, the onset of symptoms is a subjective measure that is prone to inaccuracy and recall bias. Atypical presentations of angina can bias the reported time of onset of symptoms. Second, symptoms associated with STEMI may not coincide with onset of complete occlusion of the artery. Finally, symptom-to-balloon time is likely confounded by a large number of factors, including patient characteristics, comorbidities, severity of symptoms, and familiarity with and access to the healthcare system.
Regardless of the time metric utilized, a guiding principle in STEMI management is that a decrease in time to durably restore infarct artery patency improves outcomes, although the magnitude of benefit does appear to erode as time from symptom onset increases. Any strategy chosen to improve outcomes in STEMI patients should focus on not only the efficacy of the modality used to achieve revascularization, but also the patient factors and a realistic assessment of treatment delay.
2 Time-dependent Benefit of Revascularization
The adage that 'time is tissue' holds true in most studies examining the association between delay to reperfusion and clinical outcomes. Conceptually, there is an early period of time-dependent mortality reduction within approximately 3 h from symptom onset where substantial myocardium can be salvaged with reperfusion. Based on the model developed by Gersh et al., after 6 h from symptom onset, the benefit of reperfusion therapy, while still present, becomes less time dependent and the mortality reduction versus time to reperfusion therapy slope becomes less acute. During this late period, the goal is to open the infarct-related artery, and D2B time is not as critical. Consequently, one would not want to select a reperfusion strategy that leads to a delay, shifting from a critically time-dependent phase to a less time-dependent phase of infarction, and decreasing the potential for myocardial salvage.
With this construct in mind, clinical studies have clearly demonstrated that longer D2B time delay is associated with increased mortality. A review of 29,222 patients in the National Registry of Myocardial Infarction (NRMI) 3 and 4 found that mortality is 3.0 % when D2B time is <90 min and 7.4 % when D2B time is >150 min. It has been demonstrated that several patient-related factors, such as female sex, age >70 years, diabetes mellitus, and prior PCI are associated with longer D2B time delay, likely due to atypical presentations, higher medical complexity, and more patient instability. Similar results linking D2B time to short-term and long-term mortality have been found in other clinical trials and registry analyses
Extensive efforts involving professional organizations, individual hospitals, and hospital networks have aimed to improve D2B time. For example, the American College of Cardiology (ACC) and its partners launched the D2B Alliance in 2006 as a national campaign to decrease D2B time. A study of D2B time in the National Cardiovascular Data Registry (NCDR) CathPCI registry showed that, in 2005, only 52.5 % of patients presenting to a PCI-capable hospital had D2B time <90 min compared with 76.4 % by 2008. A later study determined that even among patients with D2B time <90 min, a mortality benefit may exist in decreasing D2B time even further.Table 1 compares D2B time in various trials and registry analyses conducted over the last 2 decades.
Interestingly, symptom-to-balloon time, also known as total ischemic time, has had varying associations with morbidity and mortality in several analyses. A large Danish registry of >6,200 patients who underwent PPCI found that shorter symptom-to-balloon time was not associated with reduced mortality at 3 years, whereas there was an increase in mortality with longer FMC-to-balloon time. Similarly, among 27,000 patients from NRMI-2, there was no association between mortality and symptom-to-balloon time, but an increased mortality for D2B time >120 min was seen.
There are several reasons why an association between symptom-to-balloon time and mortality may be difficult to demonstrate. First, the onset of symptoms is a subjective measure that is prone to inaccuracy and recall bias. Atypical presentations of angina can bias the reported time of onset of symptoms. Second, symptoms associated with STEMI may not coincide with onset of complete occlusion of the artery. Finally, symptom-to-balloon time is likely confounded by a large number of factors, including patient characteristics, comorbidities, severity of symptoms, and familiarity with and access to the healthcare system.
Regardless of the time metric utilized, a guiding principle in STEMI management is that a decrease in time to durably restore infarct artery patency improves outcomes, although the magnitude of benefit does appear to erode as time from symptom onset increases. Any strategy chosen to improve outcomes in STEMI patients should focus on not only the efficacy of the modality used to achieve revascularization, but also the patient factors and a realistic assessment of treatment delay.
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