Breaking with Tradition: Is Diagnostic Angiography Really
Necessary before Primary PCI?

The superiority of primary percutaneous coronary intervention (PCI) over fibrinolytic therapy for the treatment of ST-elevation myocardial infarction (STEMI) has been demonstrated in several large studies.^1-3 Nevertheless, the preponderance of data suggest that delays in time to treatment are associated with increased morbidity and mortality in patients with STEMI.^4-6 These data have led to recording of the door-to-balloon time, i.e., the elapsed time between patient presentation and coronary angioplasty, as a measure of the efficiency of a primary PCI strategy in the community. Recently, nationwide initiatives have been proposed to decrease door-to-balloon times in an effort to improve cardiovascular outcomes.⁷ Such initiatives, however, have largely been directed at decreasing delays in emergency medical response, the diagnosis of STEMI, activation of the catheterization laboratory and transport of patients to the catheterization laboratory. Less effort has been directed at delays in revascularization that occur after patient arrival in the catheterization laboratory. As a result, relatively little data exist to guide initiatives to decrease the “artery-to-balloon” time, i. e., the time elapsed between establishment of arterial access in the catheterization laboratory and coronary angioplasty.
Diagnostic coronary angiography traditionally involves assessment of all coronary territories in multiple views to define the coronary anatomy, coronary dominance and the presence of collateral circulation; this requires engagement of both the left and right coronary arteries, as well as any coronary bypass grafts present. Often, left ventriculography is performed to evaluate left ventricular function, measure end-diastolic pressure and evaluate for the presence of mechanical complications, namely mitral regurgitation or a ventricular septal defect. Although in an ideal case all of these steps can be performed quickly, each are time-consuming, and in patients with STEMI, each may have an impact on the time to coronary revascularization. In particular, door-toballoon times may be delayed in cases in which multiple bypass grafts are present or in which the coronary arteries are anomalous or otherwise difficult to engage.
The study by Applegate et al published in this issue of the Journal of Invasive Cardiology evaluates the impact of culprit-vessel PCI without traditional diagnostic coronary angiography on door-to-balloon times at a single academic institution .8 In this well-done study, 50 patients underwent direct angiography and PCI of the coronary artery thought to be the culprit vessel for STEMI based on the electrocardiogram (ECG). Door-to-balloon times and clinical outcomes were compared to a control group of 85 patients with STEMI who underwent traditional diagnostic coronary angiography, followed by PCI of the culprit vessel. Importantly, the selection of patients for direct culprit- vessel PCI was at the discretion of the interventional cardiologist involved in the case. Likewise, in the control group undergoing traditional diagnostic coronary angiography, left ventriculography was performed at the discretion of the interventionalist. As a result, several differences in baseline characteristics were present between the study and control groups. Patients treated with direct culpritvessel PCI were slightly younger (mean age 56 vs. 60 years), and more likely to have the right coronary artery as the culprit vessel for STEMI (70% vs. 49%; p = 0.02). Coronary artery bypass graft surgery (CABG), knowledge of previous coronary anatomy and presence of cardiogenic shock were noted as factors that might influence the selection of patients for direct culprit-vessel PCI, although these variables were not significantly different between the study and control groups.
The outcomes of direct culprit-vessel PCI were similar to those in the control group in this study; furthermore, a significant decrease in door-to-balloon time was demonstrated. In 49/50 cases, the culprit vessel for STEMI was correctly identified by ECG. The use of drug-eluting stents (DES) was significantly lower in patients selected for direct culprit-vessel PCI (60% vs. 76%; p = 0.04). There was no difference in the number of deaths (2.0 vs. 1.4%; p = 0.70) between the study and control groups, and no difference in nonfatal MI, unplanned target vessel revascularization or stent thrombosis (no cases in either group). Door-to-balloon time, however, was significantly lower in the culpritvessel PCI group (66 ± 20 vs. 79 ± 28 minutes; p = 0.003), largely driven by a decrease in artery-to-balloon time (11 ± 8 vs. 18 ± 8 minutes; p < 0.001). Furthermore, the percentage of patients with a door-to-balloon time < 90 minuteswas significantly higher in the direct culprit-vessel PCI group (92% vs. 76%; p = 0.02).
One argument against direct culprit-vessel PCI in STEMI has been the possibility of precluding optimal therapy in patients whose anatomy is better suited for surgical rather than percutaneous revascularization, or in patients with mechanical complications of MI necessitating surgery. In this study population, Applegate et al report that only 8/135 (5.9%) patients from both groups were found to have threevessel or severe left main coronary artery disease (CAD) on coronary angiography. No patients were reported to have mechanical complications of MI necessitating surgery. These results are similar to those from a large study in Denmark, in which only 1/777 (0.1%) patients underwent immediate CABG following diagnostic angiography for STEMI.3 In reality, patients with mechanical complications of MI, threevessel CAD or severe left main disease cannot be taken to the operating room in a timely fashion in most cases; therefore, the interventional cardiology team must decide on a course of action to quickly achieve culprit-vessel patency followed by further coronary revascularization if and when it is appropriate. In some cases, this may be accomplished by “staging” further PCI to be performed at a later date. Alternatively, angioplasty can be performed without stenting in the culprit vessel to establish reperfusion and to allow for the temporary cessation of antiplatelet therapy without risk of stent thrombosis if CABG is recommended. In this study of direct culprit-vessel PCI, patients in the study group received stents to the culprit vessel before delineation of the full coronary anatomy; in certain situations, this may delay options for surgical revascularization until antiplatelet therapy can be safely discontinued. Given the high rate of DES use in this study, the impact of antiplatelet therapy on the risk or timing of surgery cannot be ignored. At the very least, patients with STEMI and hemodynamic instability should be evaluated for mechanical complications of MI, either by careful cardiac auscultation, left ventriculography or echocardiography prior to stent implantation.
A recent meta-analysis of 25 randomized trials in 7743 patients demonstrated that the relative reduction in mortality is greatest in STEMI patients treated earliest after symptom onset for both primary PCI and fibrinolysis.4 A complementary analysis of 23 studies reported that the mortality benefit of primary PCI over fibrinolysis was negated when the PCIrelated time-to-treatment delay was > 1 hour.⁵ A large registry analysis of almost 200,000 patients reported that the time-totreatment delay that negated the benefit of primary PCI was somewhat longer, ranging from 71–190 minutes in different subgroups.⁶ In this study by Applegate et al, the door-to-balloon time was significantly lower in patients treated with direct culprit- vessel PCI. However, a nonsignificant baseline difference in the door-to-arterial access time was present between the study and control groups. Therefore, the significant 13-minute decrease in door-to-balloon times in the direct culprit-vessel PCI group was driven by only a 7-minute decrease in arterial access-to-balloon time in the study group. Although there is strong evidence to support improvements in cardiovascular outcomes with decreased time-to-treatment in STEMI, the expected magnitude of the effect on clinical outcomes resulting from a 7-minute decrease in arterial access-to-balloon time is unclear, though on a population level, it may have a public health impact.
It is important to keep in mind that left heart catheterization and coronary angiography are invasive medical procedures which can sometimes be associated with severe complications, albeit rarely. In our efforts to improve timeto- treatment, especially in this era of scorecard medicine, we must still take care to perform medical procedures as safely as possible. Efforts to decrease arterial access-to-balloon times must not compromise patient safety. Adequate care must be taken to maintain the sterility of the procedure, obtain arterial access and perform quality angiography so that the coronary anatomy is sufficiently defined. Further care must be taken in deciding on a proper course of action following angiography, selecting equipment for the interventional procedure and in the selection of adjunctive pharmacologic therapy. This pilot study by Applegate et al is important because it establishes the safety of a strategy to pursue direct culprit-vessel PCI rather than diagnostic coronary angiography in patients with STEMI and reports a decreased time-to-treatment with such a strategy. Further data from a large-scale randomized trial may demonstrate the safety of such a strategy in a larger cohort and determine whether the time saved results in a clinically meaningful benefit on cardiovascular outcomes.