Effect of Direct Stent Implantation on Minor Myocardial Injury

Coronary stenting is established as a common technique to improve outcomes of percutaneous transluminal coronary angioplasty (PTCA) and to reduce incidence of emergency coronary artery bypass grafting after PTCA.1 The standard coronary stent implantation technique requires routine predilatation of the target lesion with a balloon catheter. This technique, although universally used, usually requires the use of a balloon and has the potential for dissections and/or other complications such as abrupt vessel closure, elastic recoil, suboptimal result, sidebranch occlusion and distal embolization.2 Although abrupt vessel closure, coronary dissection, elastic recoil and suboptimal result can be prevented with the use of stent implantation, minor myocardial injury (MMI), probably resulting from the longer ischemia duration, sidebranch occlusion and distal embolization, remains a problem using conventional implantation techniques. Cardiac troponin T (cTnT) is a regulatory contractile protein, which is not normally found in blood. Its appearance in the circulation is a clear signal of cardiac myocyte damage.3,4 The use of serum troponin T level as a means of assessing MMI, which affects the prognosis, has not been fully clarified in patients with direct stenting (stenting without predilatation). This is the first prospective, nonrandomized study to investigate the incidence of MMI following direct stent implantation. In the present study, we compared direct stenting in patients with stable angina and simple lesion morphology with the conventional implantation technique with respect to MMI and 6 month prognosis by using cTnT. METHODS Patient population. From November 1999 to April 2001, a total of 910 patients with Canadian Cardiac Society Class II stable angina pectoris underwent percutaneous coronary interventions in our institution. Only patients with type A de novo lesions in large native coronary arteries were enrolled prospectively in this nonrandomized study. Patients with renal dysfunction, pericardial disease, cardiomyopathy, unstable angina, acute myocardial infarction within 2 weeks, 12-lead resting electrocardiogram with right or left bundle branch block, paced rhythm or complete atrioventricular block, aortocoronary bypass operation within 2 weeks and recent myocarditis were excluded. Furthermore, patients with a lesion located in a vessel that had excessive proximal tortuosity and patients in whom the target lesion was highly calcified were excluded. The primary endpoint of the study was MMI in-hospital and the secondary endpoint was the major clinical events (death, acute myocardial infarction and repeat revascularization) in-hospital and at 6 months. The study protocol was approved by the local ethics committee and a written informed consent was requested of all patients before undergoing coronary interventions. Invasive procedure. Coronary angiography was made with the Judkins technique from the right femoral artery. Coronary lesions were assessed by multiple orthogonal views with coronary angiography and visually evaluated for morphologic features similar to those reported by the ACC/AHA.5 Stent implantation was performed by 3 different invasive cardiologists according to standard clinical practice. A 6 French guiding catheter was used in all patients for whom coronary intervention was decided during the coronary angiography. A standard 0.014´´ guidewire was passed through the target lesion. The decision whether to perform predilatation for other lesions that were suitable for both procedures (stenting with or without predilatation) was made by the operators. If a decision was made to proceed without predilatation, the stent was usually deployed at the nominal pressure of the stent balloon and a high-pressure balloon was subsequently used for dilatation within the stent at 14–16 atmospheres (atm). If the stent failed to cross the lesion, standard predilatation with a balloon was performed, followed by a further attempt to cross with the stent. If a decision was made to proceed with predilatation, balloon dilatation with 8 atm was performed and stent(s) were subsequently deployed. Balloon inflation time (BIT) and the number of balloon inflations were recorded during the interventions. Total BIT in seconds was obtained by adding the times of each inflation. Results before and after coronary interventions were evaluated quantitatively by coronary angiography (Philips DC). Angiographic success was defined as Electrocardiographic (ECG) monitoring. All patients were monitored continuously during the interventions and then transferred in an intensive care unit after the procedure. A 12-lead ECG was taken just before and immediately after coronary stenting for exclusion of acute ischemia. A significant ST-segment depression was defined as horizontal or down-sloping depression of ST segment > 0.1 mV and 0.08 seconds after the J point that persisted for more than 1 minute. Blood sampling. Blood samples were drawn from an antecubital vein just before the procedure and 12 and 24 hours after the procedure. Serum troponin T concentration was then measured by “Cardiac T Quantitative” equipment (Boehringer, Mannheim, Germany). The results were evaluated within 20 minutes by the “Cardiac Reader”. While the values remaining under 0.05 ngr/ml were shown as negative by the Cardiac Reader, the upper values were assessed quantitatively. Clinical follow-up. All patients were followed up during the hospital stay and then with telephone contact up to 6 months with respect to major clinical events (death, acute myocardial infarction, repeat revascularization). Deaths were classified as cardiac in origin if associated with congestive heart failure, acute myocardial infarction or sudden cardiac death (Statistical analysis. Continuous variables were expressed as means ± SD and were compared by student’s t-test. Categorical variables were compared by the Chi-square test. Comparisons were made between the direct stenting group and the stenting with predilatation group. A p-value Troponin T measurement. Basal cTnT measurements were negative in all patients. cTnT level was found to be increased in 4 out of 78 patients (5.1%) in Group I and 16 out of 76 patients (21%) in Group II at both 12 hours and 24 hours postintervention as shown in Figure 1 (p Angiographic data. A total of 176 lesions were treated with 168 stents (51 Multi-Link Duet or Tetra stents, 57 NIR stents, 33 Jostents, and 27 AVE GFX stents). There were no major complications or sidebranch occlusions during or immediately postprocedure. Furthermore, no GP IIb/IIIa agents were used during or postprocedure. Angiographic features of the 2 groups were similar except for the following procedural factors: total BIT (30.3 ± 4.6 seconds in Group I vs. 122.7 ± 4.3 seconds in Group II); number of balloon inflations (1.4 ± 0.4 inflations in Group I vs. 3.1 ± 1.1 inflations in Group II); and percent diameter stenosis (80.4 ± 2.9% in Group I vs. 84.6 ± 3.4% in Group II) (Table 3). We compared the total BIT and the number of balloon inflations in patients with or without elevation of cTnT level within the 2 groups. The total BIT was found to be significantly higher in patients with abnormal cTnT levels than in those with normal cTnT levels in Group II (120.3 ± 4.7 seconds vs. 118.2 ± 1.3 seconds, respectively; p 0.05). Furthermore, there was no statistically significant difference with respect to the number of balloon inflations in patients with normal and abnormal cTnT levels in either group (1.2 ± 0.2 inflations vs. 1.3 ± 0.4 inflations in Group I, p > 0.05; 3.2 ± 0.9 inflations vs. 3.0 ± 1.4 inflations in Group II, p > 0.05) Clinical follow-up. There were no complications during or after the procedure in any patient. In Group II, two patients with abnormal cTnT levels died suddenly by the end of the sixth month. No major clinical events were seen during the in-hospital period. Six month clinical outcomes were obtained in 96.6% of patients with a mean duration of 6.1 ± 1.1 months. During this period, ten patients (9 with normal and 1 with abnormal cTnT level, p > 0.05) in Group I and 12 patients (8 with normal and 4 with abnormal cTnT level, p > 0.05) in Group II underwent repeat revascularization because of refractory chest pain. None of the patients had acute myocardial infarction. Therefore, the major clinical event rate was 12.8% in Group I and 18.4% in Group II (p > 0.05). DISCUSSION The typical profile of cardiospecific cTnT elevation after an ischemic trauma to the myocardium makes it a suitable marker for detecting MMI following coronary interventions. Previous studies comparing balloon angioplasty and stenting with predilatation with respect to MMI reported that cTnT was elevated in 3.4–29% in patients with balloon angioplasty and 8.9–44% of those undergoing stenting with predilatation.6–12 This wide range probably resulted from differences in the methods or the inclusion criteria used in these studies. In our study, we selected only patients with class II stable angina pectoris and simple lesion morphology and eliminate all conditions (acute myocardial infarction or cardiac surgery within two weeks, unstable angina pectoris, cardiomyopathy, unsuccessful stent delivery, etc.) that could cause cTnT release. For this reason, we believe that this study reflects the MMI better than those mentioned above. In our present report, elevation of cTnT was found in 5.1% of the patients undergoing stenting without predilatation and in 21% of those undergoing stenting with predilatation. Both amount and frequency of cTnT release were significantly lower in patients with direct stenting. Though there was an increased trend toward MCE in the stenting with predilatation group than in the direct stenting group, this did not reach statistical significance, which is consistent with previously published data.13 MMI and its association with patient prognosis after coronary interventions has not yet been clarified. MMI in this setting could result from embolization of the plaque microparticles, debris of intravascular friable material, clots or cholesterol crystals. Vessel injury due to procedural factors such as BIT and balloon inflation pressure may result from platelet activation and micro-embolization. Minor in-lab complications (transient vessel closure, sidebranch compromise, coronary dissection) may also take part in the occurrence of small zones of necrosis due to sudden mismatch between metabolic requirements of the myocardium and coronary blood flow.14 These microinfarct areas can create zones of slow conduction that increase the susceptibility to ventricular arrhythmia via microreentrant circuits.15 Additionally, ventricular arrhythmia after microembolization also may be triggered by a focal mechanism.16 Thus, it is conceivable that microinfarcts associated with minor increases in cardiac enzymes provide a nidus for ventricular arrhythmia via micro-reentry or focal mechanism.15,16 The interruption of collateral blood flow by embolization has been shown to potentiate the ischemic effects of subsequent coronary occlusion.17 This can lead to the higher incidence of ventricular arrhythmia and a larger infarct size. In other words, the initial microembolization sensitizes the heart to the effect of a subsequent ischemic insult.18 In summary, direct stenting is feasible and safe in selected lesions. It has many advantages over the conventional implantation techniques, such as shorter ischemia duration and less platelet activation due to less vessel injury from balloon inflations.18,19 Moreover, it aims to reduce procedural time (ischemic, fluoroscopic) and cost, saving the balloon needed for predilatation. There may be some specific procedure-related complications of direct stenting, such as stent loss, that may occur when the stent does not cross the lesion. However, this complication can be almost completely avoided with the right lesion selection and excellent catheter backup support.20 The present study showed that MMI probably occurs less frequently after direct stenting in selected patients. Study limitations. Major limitations of the present study are the small number of patients in each group and the nonrandomized study design. Furthermore, all patients were followed for only 6 months. Nevertheless, this single-center experience implies that the incidence of MMI associated with interventions seems to be lower in patients undergoing direct stenting. Therefore, a randomized study should be performed to better determine the impact of this technique on long-term outcomes.

1. Pepine CJ, Holmes DR. Coronary artery stents. J Am Coll Cardiol 1996;28:782–794. 2. Pentuois D, Guérin Y, Funk F, et al. Direct stent implantation without predilatation using the Multi-Link stent. Am J Cardiol 1998;82:1437–1440. 3. Mair J, Dienstl F, Pushendorf B. Cardiac troponin in the diagnosis of cardiac injury. Crit Rev Clin Lab Sci 1992;29:31–57. 4. Hillis WS, Birnie D, Cocherty A. Troponin T and myocardial damage. Br J Cardiol 1993;1:16–21 and 16–22. 5. Ryan TJ, Bauman WB, Kennedy JW, et al. Guidelines for percutaneous transluminal coronary angioplasty: A report of the American Heart Association/American College of Cardiology Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Committee on Percutaneous Transluminal Coronary Angioplasty). Circulation 1993;88:2987–3007. 6. Ravkilde J, Nissen H, Mickley H, et al. Cardiac troponin T and CK-MB mass release after visually successful percutaneous transluminal coronary angioplasty in stable angina pectoris. Am Heart J 1994;127:13–20. 7. Talasz H, Genser N, Mair J, et al. Side-branch occlusion during percutaneous transluminal coronary angioplasty. Lancet 1992;339:1380. 8. Ohnishi N, Iwasaki K, Kusachi S, et al. Low incidence of minor myocardial damage associated with coronary stenting detected by serum troponin T comparable to that with balloon coronary angioplasty. Jpn Heart J 1998;39:139–146. 9. Vecchia LL, Bedogni F, Finocchi G, et al. Troponin T, troponin I and creatine kinase MB mass after elective coronary stenting. Coron Art Dis 1996;7:535. 10. Kou-Gi Shyu, Pei-Liang Kuan, Jun-Jack Cheng, Chi-Ren Hung. Cardiac troponin T, creatine kinase, and its isoform release after successful percutaneous transluminal coronary angioplasty with or without stenting. Am Heart J 1998;135:862–867. 11. Johansen O, Brekke M, Strømme JH, et al. Myocardial damage during percutaneous transluminal coronary angioplasty as evidenced by troponin T measurements. Eur Heart J 1998;19:112–117. 12. Karim MA, Shinn M, Oskarsson H, et al. Significance of cardiac troponin T release after percutaneous transluminal coronary angioplasty. Am J Cardiol 1995;76:521. 13. Carrie D, Khalife K, Citron B, et al. Comparison of direct coronary stenting with and without balloon predilatation in patients with stable angina pectoris. Am J Cardiol 2001;87:693–698. 14. Abdelmeguid AE, Topol EJ, Whitlow PL, et al. Significance of mild transient release of creatine kinase MB fraction after percutaneous interventions. Circulation 1996;94:1528–1536. 15. Pogwizd SM. Focal mechanisms underlying ventricular tachycardia during prolonged ischemic cardiomyopathy. Circulation 1994;90:1141–1158. 16. Kaplinsky E, Ogawa S, Balke W, Dreifus L. Two periods of early ventricular arrhythmia in the canine acute myocardial infarction model. Circulation 1979;60:397–403. 17. Euler DE, Prood CE, Spear JF, Moore EN. The interruption of collateral blood flow to the ischemic myocardium by embolization of a coronary artery with latex: Effect on conduction delay and ventricular arrhythmias. Circ Res 1981;49:97–108. 18. Jose Mari de la Torre H, Isabel G, Felipe RE, et al. Evaluation of direct stent implantation without predilatation by intravascular ultrasound. Am J Cardiol 2000;85:1028–1030. 19. Figula H, Mudra H, Reifart N, Werner GS. Direct stenting without predilatation: A new therapeutic approach with a special balloon catheter design. Cathet Cardiovasc Diagn 1998;43:245–252. 20. Atmaca Y, Altin T, Özdöl C, et al. Direct Stent Implantation in Acute Coronary Syndrome. J Invas Cardiol 2002;14:308–312.