Direct Stenting May Limit Myocardial Injury During Percutaneous Coronary Intervention<br />
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There has been a dramatic increase in the use of intracoronary stents as the primary percutaneous treatment strategy for coronary lesions. This shift was supported by evidence demonstrating improved acute and long-term outcomes with stenting compared with balloon angioplasty alone.1,2 Direct stenting (DS), without balloon predilatation, has reportedly led to a reduction in overall cost, contrast volumes, procedural and radiation exposure times.3–9 However, there has been no demonstrable difference in the majority of studies comparing DS and conventional stenting with balloon predilatation (PD) for the endpoint of major adverse cardiac events (MACE) at 6-month follow-up.7,9–12 The technique of DS has the added theoretical advantages of shorter ischemic time, reduced trauma and dissection to the vessel wall and the containment of clot and atherosclerotic plaque debris, thereby minimizing potential distal embolization and myocardial cell necrosis. Post-procedural myocardial cell injury, as reflected by cardiac marker elevation, has been shown to be of prognostic value in its association with a poor clinical outcome,13–19 but few reports of DS have specifically addressed this issue.10 Therefore, our aim was to evaluate differences in myocardial cell injury following DS compared to stenting with PD, as reflected by post-procedural cardiac troponin I (cTnI) release, and to assess any differences in clinical outcomes between the two groups. METHODS Patient population. We studied a total of 355 consecutive patients presenting with symptoms of both stable and unstable angina and undergoing percutaneous coronary stenting at our institution over a period of 1 year between June 1998 and May 1999. We excluded patients presenting with acute myocardial infarction (AMI), patients undergoing percutaneous coronary intervention (PCI) on non-native vessels (i.e., grafts) and patients undergoing interventional strategies other than, or in addition to, coronary stenting (e.g., rotational atherectomy). Patients who were recruited to other clinical trials within our department and patients with incomplete sets of pre- and post-PCI cTnI data were also excluded. The decision to predilate or use direct stenting was made by each individual operator on subjective assessment of the angiographic appearance of the lesion to be treated. Direct stenting was deemed appropriate in native coronary arteries > 3 mm diameter and in the absence of significant lesion calcification, total vessel occlusion and/or excessive vessel tortuosity (angulation > 45°). All interventional procedures were performed by experienced operators and according to established practice at our center, using the femoral arterial approach with 5,000–10,000 units of heparin administered at the outset. All patients were pretreated with aspirin and received either ticlopidine (250 mg twice daily for the first week and 250 mg once daily for the second week) or clopidogrel (75 mg once daily for 2 weeks). Procedural angiographic success was defined as a residual stenosis of Cardiac troponin I sample collection and analysis. Blood was sampled for cTnI immediately before and at 6, 14 and 24 hours following the interventional procedure. Samples were centrifuged at 2000 g for 10 minutes and the serum was separated and stored at -20 °C prior to analysis. Quantitative cTnI analysis was performed using the Bayer Immuno-1™ heterogeneous magnetic separation assay (Bayer Diagnostics, Newbury, United Kingdom). The assay had a detection limit of 0.1 µg/L, an analytical range up to 200 µg/L and a recommended clinical discriminant cut-off value of 0.2 µg/L for significant myocardial injury (cTnI >= 0.9 µg/L is considered diagnostic of acute MI). Statistical analysis. Continuous variables were expressed as means ± standard deviation. Non-continuous variables such as cTnI concentrations were expressed as medians (interquartile range). Binary outcome variables were reported as percentages. The Mann-Whitney U-test was used to compare peak median cTnI concentrations in the DS and PD groups. Pearson’s Chi-square test was used for comparison of proportional data. Data analysis was performed using the StatView 4.5 software package (Abacus Concepts, Inc., Berkeley, California). A p-value 0.2 µg/L and were excluded from further analysis. Of the remaining 311 patients (440 vessels), DS was considered appropriate and feasible by the operator in 114 patients (37%) [160 vessels (36%)]. DS was performed successfully in a total of 107 patients (94%) [149 vessels (93%)]. Sixty-six patients (62%) underwent single-vessel intervention and 41 patients (38%) had multivessel intervention. Eight of the patients (19.5%) in the DS group undergoing multivessel intervention required predilatation in at least 1 of the vessels and were subsequently analyzed on an intention-to-treat basis. All 7 patients (6%) and 11 vessels (7%) crossing over from the DS to the PD group were successfully stented following balloon predilatation. Balloon predilatation followed by stenting was performed in a total of 204 patients (291 vessels). A total of 120 patients (59%) underwent single-vessel intervention and 84 patients (41%) within the PD group had multivessel intervention. There was no statistically significant difference in the proportion of multivessel interventions between the two groups (p = 0.14). The DS and PD groups were well matched in terms of preprocedural clinical and angiographic characteristics, except for a greater proportion of diabetic patients in the PD group (21%) compared to the DS group (11%) (p 0.2 µg/L in 11 patients (10%) in the DS group and 53 patients (26%) in the PD group (X2 = 58.6; p 0.9 µg/L (MI cut-off value) occurred in 3 patients (2.8%) in the DS group and 7 patients (3.4%) in the PD group (p = NS). In-hospital MACE occurred in 1 patient (0.9%) in the DS group (1 QWMI) and 6 patients (3%) in the PD group (3 QWMI, 1 re-PCI, 2 CABG). At follow-up from 6–18 months, MACE occurred in 9 patients (8%) in the DS group (0 deaths, 1 QWMI, 7 re-PCI, 1 CABG) compared to 30 patients (15%) in the PD group (2 deaths, 3 QWMI, 21 re-PCI, 4 CABG) (X2 = 38.5; p = 0.02). All 311 patients (100%) were seen clinically at a mean follow-up period of 45 ± 12 weeks. A total of 268 patients (86%) had a follow-up exam at 18 months post-PCI at the time of this manuscript submission. We used a multivariate model to assess the relationship between outcome and the presence of diabetes (p = 0.08) and prolonged balloon inflation (> 60 seconds) (p > 0.5), and found no statistically significant association between either variable and our study endpoints. DISCUSSION With the advent of more sophisticated guide catheter and stent technology, direct stent deployment without the need for balloon predilatation has become increasingly favored by many interventional cardiologists. Several reports have previously highlighted the benefit of direct stenting in terms of reducing cost, procedural and radiation exposure times,3–9 but none have demonstrated a convincing difference in clinical outcomes or restenosis rates compared to stenting with balloon predilatation.20 Our study, in addition to confirming the safety and feasibility of the DS technique, has also demonstrated significantly lower post-procedural cTnI release following DS compared to traditional stenting with balloon predilatation. This observation is not totally surprising since the direct “pavementing” of the lesion, with containment of clot and plaque material by the stent, would be expected to limit distal embolization and myocardial cell injury. This approach is particularly relevant to intervention within diseased vein grafts, where the potential for distal embolization is significantly greater than in native vessels. Hence, we have deliberately excluded this subset from our series in order to avoid a potential confounding factor that may have influenced the results. The prognostic implications of periprocedural myocardial injury have been well documented, where cardiac marker elevation post-PCI is associated with a higher incidence of adverse events.13–19 It is interesting that our data have shown a significantly lower incidence of MACE both in-hospital and at up to 18-month follow-up in the DS group, which had lower cTnI post-PCI levels compared to the PD group. Clearly, the main limitation of our study is the lack of randomization in the 2 groups. Nevertheless, the patients within the 2 groups were well matched, apart from a higher proportion of diabetic patients in the PD group. It is generally recognized that patients with diabetes have a greater likelihood of adverse cardiac events following PCI compared to non-diabetics, but the majority of the data preceded the era of coronary stenting and glycoprotein IIb/IIIa receptor inhibition, both of which have dramatically improved the outcomes of PCI. We did not demonstrate any significant relationship between the presence of diabetes and adverse outcomes following PCI in our cohort of patients, but we accept that the relatively small proportion of diabetics within each of our 2 groups limits the relevance of this statistical observation. In addition, the number of diabetic patients within each of the 2 groups receiving abciximab, although equally distributed (DS, n = 7 (63%); PD, n = 14 (58%); p = 0.2), is too small to discern a statistically significant difference between the 2 groups. Our relatively low rate of glycoprotein IIb/IIIa receptor inhibitor use reflects the fact that this study was commenced before the benefit of abciximab was established in PCI. Abciximab was, therefore, predominantly used as a “bail-out” rather than electively in all but the latter part of the study. Furthermore, diabetic patients are theoretically more likely to have more complex and diffuse coronary disease, but we found no significant difference in the distribution of target lesion site or lesion complexity between the 2 groups. However, we accept that unintentional operator bias may have influenced selection for direct stenting as this cannot be excluded with any certainty without a randomized protocol. Despite the inherent problems of a non-randomized observational design, this study is strengthened by the fact that we specifically assessed post-PCI release of cTnI, which is widely accepted as a strong prognostic marker of outcome. Our findings are, therefore, of sufficient significance to justify a larger, randomized trial to evaluate post-procedural cardiac troponin release and clinical outcome beyond 6 months, following direct stenting compared to stenting with balloon predilatation. Should the results of such a trial mirror our own experience, they would definitively support the already increasing trend among the interventional community toward the direct deployment of coronary stents both in diseased vein grafts and suitable native vessels.

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