- Email: [email protected]
Frequency and prognostic value of cardiac troponin I elevation after coronary stenting
Frequency and Prognostic Value of Cardiac Troponin I Elevation After Coronary Stenting Eric Garbarz, MD, Bernard Iung, MD, Guillaume Lefevre, MD, Yasuhairo Makita, MD, Bruno Farah, MD, Pierre Michaud, MD, Hanafi Graine, MD, and Alec Vahanian, MD Mild myocardial injuries after coronary angioplasty are associated with adverse late outcomes. The incidence and prognostic value of this phenomenon when using cardiac troponin I (cTnI) after stent implantation is unknown. We studied cTnI and creatine kinase (CK) release in 109 patients after stenting. Clinical success was achieved in 103 patients (94%). In-hospital major adverse coronary events were: death in 1 patient, Q-wave myocardial infarction in 1 patient, and non–Q-wave myocardial infarction in 2 patients. Twenty-nine patients (27%) had postprocedural cTnI increase, 16 (15%) had CK elevation. No preprocedural variables predicted marker elevation. Marker release was related to the occurrence of in-lab complications (59% vs 29% [p ⴝ 0.004 for cTnI] and 69% vs 32% [p ⴝ 0.011 for CK]). In 34% no explanation was found for cTnI increase. Success was more frequent in patients without cTnI eleva-
tion (100% vs 86%, p <0.001). The negative predictive value of cTnI increase was 100% for in-hospital major adverse coronary events (MACE), whereas its positive predictive value was 14%. cTnI and CK concordant elevation was associated with more intra- and postprocedural adverse events. During a mean follow-up of 8 ⴞ 3 months, major adverse coronary events were: death in 2 patients, myocardial infarction in 2 patients , and repeat PTCA in 8 patients. cTnI elevation was not predictive of these late MACE. cTnI elevation is common after stenting, and is related to the occurrence of in-lab complications. Its isolated elevation is not a good predictor of MACE. Patients with concordant cTnI and CK elevation seem to be at higher risk of in-hospital MACE. 䊚1999 by Excerpta Medica, Inc. (Am J Cardiol 1999;84:515–518)
everal recent studies have suggested that after percutaneous transluminal coronary angioplasty, S minor myocardial damage, usually defined by post-
limit of normal were not included in the study. Patients with elevated baseline cTnI were not excluded. Coronary angioplasty and stenting: These procedures were performed using standard techniques. Our first choice of coronary stent was the GFX (AVE, Santa Rosa, California), which was used in 60% of cases. Intravenous aspirin and an in-lab bolus dose of heparin were routinely administered. Abciximab use was left to the discretion of the supervising physician. After the procedure, all patients received aspirin and ticlopidin for a 1-month period. All angiograms were reviewed by 2 experienced operators blinded to the results of marker determination. cTnI, CK, and CK-MB measurements: Blood samples were collected in heparinized tubes (Vacutainer, Becton Dickinson, Paris, France) 2 hours before, and then 8 and 24 hours after stent procedure and immediately sent to the laboratory. All measurements of cTnI were obtained by immunoassay on the Stratus II analyser (Dade Behring, Paris, France) using specific antibodies raised against cardiac epitopes of troponin I. Between-run coefficient of variation at approximately 0.60, 0.90 g/L was 12.3% and 6.6%, respectively. We previously described that in our institution the upper limit of normal for cTnI is 0.30 g/L.7,8 Moreover, we also measured cTnI in 20 control patients before and after catheterization. These patients had either angiographically normal coronary arteries (n ⫽ 10) or coronary artery disease, but had not undergone an interventional procedure at the time of catheterization (n ⫽ 10). Although some patients in this control group had mild cTnI changes, none was of a magnitude of ⱖ0.3 g/L. Consequently, a postprocedural
procedural creatine kinase (CK) or its MB subfraction (CK-MB) mild elevation, is associated with adverse late outcome.1,2 Nevertheless, only a few data are available concerning myocardial marker elevation after stent implantation,3 although this device is very often used in contemporary practice. Cardiac troponin I (cTnI), a regulatory contractile protein, is a very specific and sensitive marker of myocardial damage.4 It has been shown to have a prognostic value beyond CK and CK-MB in acute coronary syndromes.5,6 However, little is known about cTnI release after coronary intervention, particularly after coronary stenting. This study therefore was undertaken to prospectively evaluate the frequency, correlates, and prognostic significance of cTnI elevation after stent implantation.
METHODS
Patients: The study population consisted of 109 consecutive patients who had coronary angioplasty with concomitant stent implantation in our institution. Patients who had myocardial infarction in the previous 5 days and persistent CK elevation above the upper
From the Departments of Cardiology and Biochemistry, Tenon Hospital, Paris, France. Manuscript received January 22, 1999; revised manuscript received April 19, 1999, and accepted April 21, 1999. Address for reprints: Eric Garbarz, MD, Department of Cardiology, Tenon Hospital, 4 rue de la Chine, 75020 Paris, France. ©1999 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 84 September 1, 1999
0002-9149/99/$–see front matter PII S0002-9149(99)00369-0
515
TABLE I Angiographic Characteristics Lesion ACC/AHA classification A B1 B2 C Bifurcation lesion Vessel diameter ⬍3 mm TIMI 0 or 1 Saphenous venous graft ⬎1 vessel stented Bailout stenting Abciximab Stent length (mm) Inflation time (s)
TABLE II In-Lab Complications for the Whole Cohort 11 33 48 17 18 15 13 3 3 5 28 19 396
(10%) (30%) (44%) (16%) (17%) (14%) (12%) (3%) (3%) (4.5%) (26%) ⫾ 13 ⫾ 307
ACC/AHA ⫽ American College of Cardiology/American Heart Association; TIMI ⫽ Thrombolysis In Myocardial Infarction trial.
increase in cTnI ⱖ0.3 g/L was considered an ischemic insult. Plasma samples obtained after centrifugation were also analyzed for total CK and CK-MB by enzymatic methods (Vitros 950, Ortho Clinical Diagnostic, Roissy, France). The upper reference values for CK and CK-MB activity were 180 and 16 U, respectively, according to manufacturer’s instructions. In-hospital events: Major adverse coronary events, i.e. death, nonfatal myocardial infarction, or emergency revascularizations were recorded for the purpose of this study. Myocardial infarction was defined by the appearance of a new Q wave in at least 2 continuous leads in the electrocardiogram and/or by an elevation of CK ⱖ3 times above the upper limit of normal, with a concordant CK-MB fraction elevation (i.e., ⱖ5%). Procedural success was defined as a residual stenosis ⬍30% with a Thrombolysis In Myocardial Infarction trial grade 3 flow. Clinical success was defined as a successful procedure without inhospital major adverse coronary events. Follow-up: Inclusions ended in November 1997 and follow-up data collection was performed in June 1998 through visits at our outpatient clinic or by telephone interviews with the patients’ attending physicians. Statistical analysis: Quantitative variables are expressed as mean ⫾ SD. cTnI and CK were expressed as median (25th to 75th percentiles) due to the skewness of their distribution. Comparisons between groups used the Mann-Whitney U test for quantitative variables and the chi-square or Fisher’s exact test for qualitative variables. Comparisons of values of cTnI and CK before and after stenting used the Wilcoxon test. Univariate analysis of predictive factors determining postprocedural CK and cTnI elevation included patients’ baseline clinical and angiographic characteristics (Table I) along with in-lab complications (Table II). Analysis was performed with CSS Statistica software (Statsoft Inc., Tulsa, Oklahoma). A p value ⬍0.05 was considered significant.
RESULTS
Baseline characteristics: Mean age was 61 ⫾ 12 years (range 37 to 84). Ten patients (9%) were women. Fifty patients (46%) presented with unstable
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Occlusive dissection Thrombus No reflow Side-branch occlusion Hypotension requiring vasopressors Sustained ventricular arrhythmia
5 3 7 26 14 1
(4.5%) (3%) (6.5%) (24%) (13%) (1%)
TABLE III In-Lab Complications According to Markers Status cTnI⫹ In-Lab Complications None Side-branch occlusion No reflow Occlusive dissection Thrombus Hypotension requiring pressors Sustained ventricular arrhythmia
cTnI⫺
CK⫹ (n ⫽ 10)
CK⫺ (n ⫽ 19)
CK⫹ (n ⫽ 6)
CK⫺ (n ⫽ 74)
1 (10%) 5 (50%)
9 (47%) 5 (28%)
3 (50%) 2 (33%)
54 (73%) 14 (19%)
3 1 2 3
1 (5.6%) 2 (11%) 0 4 (22%) 1
(30%) (10%) (20%) (30%)
1 (10%)
0
0 0 0 (17%) 0
3 2 1 6
(4%) (3%) (1%) (8.2%) 0
⫹ ⫽ marker increase; ⫺ ⫽ absence of marker increase.
angina, whereas 59 (54%) underwent coronary angioplasty and stenting for stable angina and/or a positive stress test. Mean left ventricular ejection fraction was 54 ⫾ 10% (range 18% to 72%). Forty-five patients (41%) had 1-vessel disease, and 45 (41%) and 19 (18%) had 2- and 3- vessel disease, respectively. Baseline angiographic characteristics are summarized in Table I. The main reasons for stenting were: systematic in 21 patients (19%), elastic recoil in 35 (32%), nonocclusive dissection in 48 (44.5%), and bailout in 5 (4.5%). Abciximab was given to 28 patients (26%), either prophylactically in 23 (21%) or as bailout treatment in 5 (5%). Procedural outcome: Overall, the procedure was successful in 105 patients (96%). In-lab complications for the whole cohort are presented in Table II. Myocardial marker determination and correlates:
Median values of cTnI (g/L) were 0 (0 to 0) at baseline, 0 (0 to 0.9) at 8 hours (p ⫽ 0.008 vs baseline), and 0 (0 to 1.3) at 24 hours (p ⫽ 0.003 vs baseline). With regard to CK (U), the median values were: 59 (29 to 93) at baseline, 60 (37 to 112) at 8 hours (p ⫽ 0.17 vs baseline), and 69 (35 to 120) at 24 hours (p ⫽ 0.02 vs baseline). An increase in cTnI ⬎0.3 g/L at 8 and/or 24 hours was observed in 29 patients (27%). CK elevation was seen in 16 patients (15%). Only 10 patients (9%) had concordant marker elevation, whereas 19 (17%) had isolated cTnI release and 6 (5%) had CK release without cTnI elevation. The relation between in-lab complication and postprocedual marker status is detailed in Table III. Using univariate analysis, we found no preprocedural clinical or angiographic variables that predicted cTnI or CK elevation. Instead, marker release was related to the occurrence of in-lab complications: 65% of patients with an increase in cTnI had at least 1 in-lab SEPTEMBER 1, 1999
complication, whereas this was the case in only 29% of patients without cTnI elevation (p ⫽ 0.004). The respective figures for CK were 75% and 32% (p ⫽ 0.011). Total inflation time, stent length, and absence of abciximab use were not predictors of marker elevation. The occurrence of at least 1 in-lab complication was observed more frequently in patients who had release of both markers than in those who had either isolated cTnI, isolated CK, or no marker elevation; the respective values were 90%, 53%, 50%, and 27% (p ⫽ 0.001). Among patients who had an isolated increase in cTnI, 9 (47%) had no in-lab complications. In-hospital outcome: One patient died (1%) after left main retrograde dissection, 1 sustained a Q-wave myocardial infarction (1%), and 2 (2%) had a non–Qwave myocardial infarction. The 4 patients with inhospital major adverse coronary events had concordant marker release. Overall, clinical success was observed in 103 patients (94%) and was more frequent in patients who did not have postprocedural cTnI increase (100% vs 86%, p ⬍0.001). Thus, the negative predictive value of postprocedural cTnI elevation was 100%. Conversely, the positive predictive value of isolated cTnI elevation for the occurrence of in-hospital major adverse coronary events was low, only 14%. However, the positive predictive value increased to 40% in patients with concordant marker elevation. Follow-up: Follow-up was obtained in 97% of patients (mean duration 8 ⫾ 3 months). During this period of time, 2 patients (2%) died after a myocardial infarction and 8 (7%) underwent repeat coronary angioplasty. Postprocedural elevated cTnI was not a predictor of these late events.
DISCUSSION The results of this preliminary study show that cTnI elevation is common after coronary stenting and is related to the occurrence of in-lab complications. The negative predictive value of cTnI elevation for the development of in-hospital major adverse coronary events was high, whereas our results suggest that its positive predictive value seems to be low. Frequency of marker elevation: The CK elevation rate of 15% in this study is within the usually reported range between 8% and 15%.9 With regard to cardiac troponin release after coronary angioplasty, the few data available are conflicting. Cardiac troponin T release has been reported to occur between 0% and 44% after uncomplicated coronary angioplasty.10 –12 Data concerning cTnI release in a coronary angioplasty setting are even more sparse. In our series, the incidence of cTnI elevation was 27%. Hunt et al13 did not find significant cTnI elevation in a cohort of 22 patients who had a successful coronary angioplasty procedure for stable or unstable angina. Correlates of marker elevation: In studies using CK or CK-MB as markers of myocardial injuries, enzyme elevation was strongly correlated with the development of in-lab procedural complications.1,14 The other correlates were1–3,15: age, recent myocardial infarction or unstable angina, multivessel disease, complex lesions, and multivessel procedures. CK/CK-MB eleva-
tion is seen more frequently with the use of new devices, such as directional and rotational atherectomy, but the influence of stenting remains largely unknown.3 With regard to cardiac troponins release, predictors are not as well characterized. Cardiac troponin T elevation has been linked to side-branch occlusion and to inflation times.10 –12 However, in the present study the only correlate of cTnI elevation was the occurrence of in-lab complications. Finally, as was observed for CK/CK-MB,16 in 47% of cases we found no explanation for the isolated elevation of cTnI. This may be related to the clinical and experimental data that have shown that the release of a small amount of cTnI could be detected after myocardial transient ischemia without cell necrosis.17,18 Taken together, these facts could lead to the conclusion that cTnI may be an oversensitive marker in the setting of coronary angioplasty and stenting. On the other hand, this study shows that there is a high rate of in-lab complications whenever concordant marker elevation is seen. Clinical implications: The negative predictive value of cTnI elevation for in-hospital major adverse coronary events was excellent. On the other hand, our results suggest that the positive predictive value of the isolated postprocedural elevation of cTnI was low. However, the concordant elevation of both cTnI and CK/CK-MB could help to identify a small group of patients requiring particular attention after the procedure since all patients who had in-hospital major adverse coronary events were in this group. Study limitations: Our sample size is small, and therefore the possibility of a type II error is high when considering the relation between cTnI elevation and outcome. We defined a postprocedural non–Q-wave myocardial infarction as an increase in total CK ⬎3 times the upper limit of normal, with a concordant elevated CK-MB fraction. Although previous studies have used the same criteria as we have,9 a recent consensus statement3 defined procedure-related myocardial infarction as a CK-MB elevation 3 times the laboratory norm. 1. Abdelmeguid A, Topol E, Whitlow P, Sapp S, Ellis S. Significance of mild transient release of creatine kinase-MB fraction after percutaneous coronary interventions. Circulation 1996;94:1528 –1536. 2. Kong T, Davidson C, Meyers S, Tauke J, Parker M, Bonow R. Prognostic implication of creatine kinase elevation following elective coronary artery interventions. JAMA 1997;277:461– 466. 3. Califf R, Abdelmeguid A, Kuntz R, Popma J, Davidson C, Cohen E, Kleiman N, Mahaffey K, Topol E, Pepine C, Lipicky R, Granger C, Harrington R, Tardiff B, Crenshaw B, Bauman R, Zuckerman B, Chaitman B, Bittl J, Ohman M. Myonecrosis after revascularization procedures. J Am Coll Cardiol 1998;31:241– 251. 4. Coudrey L. The troponins. Arch Intern Med 1998;158:1173–1180. 5. Antman E, Tanasijevic M, Thompson B, Schactman M, McCabe C, Cannon C, Fischer G, Fung A, Thompson C, Wybenga D, Braunwald E. Cardiac-specific troponin-I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med 1996;335:1342–1349. 6. Olatidoye A, Wu A, Feng Y, Waters D. Prognostic role of troponin T versus I in unstable angina for cardiac events with meta-analysis comparing published studies. Am J Cardiol 1998;81:1405–1411. 7. Lefe`vre G, Graı¨ne H, Garbarz E, Abbas A, Vahanian A, Etienne J. Comparaisons analytique et diagnostique de deux dosages de l’isoenzyme MB de la cre´atine kinase et de deux dosages de la troponine I par me´thode immunoenzymologique. Immunoanal Biol Spe´c 1998;13:167–173. 8. Wu A, Feng Y. Biochemical differences between cTnT and cTnI and their
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significance for diagnosis of acute coronary syndromes. Eur Heart J 1998;19 (suppl N):N25–N29. 9. Abdelmeguid A, Topol E. The myth of the myocardial “infarctlet” during percutaneous coronary revascularization procedures. Circulation 1996;94:3369 – 3375. 10. Karim M, Shinn M, Oskarsson H, Windle J, Deligonul U. Significance of cardiac troponin T release after percutaneous transluminal coronary angioplasty. Am J Cardiol 1995;76:521–523. 11. Johansen O, Brekke M, Strømme JH, Valen V, Seljeflot I, Skjæggestad ø, Arnesen H. Myocardial damage during percutaneous transluminal coronary angioplasty as evidenced by troponin T measurements. Eur Heart J 1998;19:112– 117. 12. Genser N, Mair J, Friedrich G, Talasz H, Moes N, Mu¨hlberger V, Puschendorf B. Uncomplicated successful percutaneous transluminal coronary angioplasty does not affect cardiac troponin T plasma concentrations. Am J Cardiol 1996;78:127–128. 13. Hunt A, Chow S, Shiu M, Chilton D, Cummins B, Cummins P. Release of creatine kinase-MB and cardiac specific troponin-I following percutaneous transluminal coronary angioplsty. Eur Heart J 1991;12:690 – 694.
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14. Talasz H, Genser N, Mair J, Dworzak E, Friedrich G, Moes N, Mu¨hlberger
V, Puschendorf B. Side-branch occlusion during percutaneous transluminal coronary angioplasty. Lancet 1992;339:1380 –1382. 15. Kugelmass A, Cohen D, Moscucci M, Piana R, Senerchia C, Kuntz R, Baim D. Elevation of the creatine kinase myocardial isoform following otherwise successful directional coronary atherectomy and stenting. Am J Cardiol 1994;74: 748 –754. 16. Klein L, Kramer B, Howard E, Lesch M. Incidence and clinical significance of transient creatine kinase elevations and the diagnosis of non-Q wave myocardial infarction associated with coronary angioplasty. J Am Coll Cardiol 1991;17: 621– 626. 17. Bleier J, Vorderwinkler KP, Falkensammer J, Mair P, Dapunt O, Puschendorf B, Mair J. Different intracellular comparmentations of cardiac troponins and myosin heavy chains: a causal connection to their different early release after myocardial damage. Clin Chem 1998;44:1912–1918. 18. Feng YJ, Chen C, Fallon JT, Lai T, Chen L, Knibbs DR, Waters DD, Wu AH. Comparison of cardiac troponin I, creatine kinase-MB, and myoglobin for detection of acute ischemic myocardial injury in a swine model. Am J Clin Pathol 1998;110:70 –77.
SEPTEMBER 1, 1999
tion (100% vs 86%, p <0.001). The negative predictive value of cTnI increase was 100% for in-hospital major adverse coronary events (MACE), whereas its positive predictive value was 14%. cTnI and CK concordant elevation was associated with more intra- and postprocedural adverse events. During a mean follow-up of 8 ⴞ 3 months, major adverse coronary events were: death in 2 patients, myocardial infarction in 2 patients , and repeat PTCA in 8 patients. cTnI elevation was not predictive of these late MACE. cTnI elevation is common after stenting, and is related to the occurrence of in-lab complications. Its isolated elevation is not a good predictor of MACE. Patients with concordant cTnI and CK elevation seem to be at higher risk of in-hospital MACE. 䊚1999 by Excerpta Medica, Inc. (Am J Cardiol 1999;84:515–518)
everal recent studies have suggested that after percutaneous transluminal coronary angioplasty, S minor myocardial damage, usually defined by post-
limit of normal were not included in the study. Patients with elevated baseline cTnI were not excluded. Coronary angioplasty and stenting: These procedures were performed using standard techniques. Our first choice of coronary stent was the GFX (AVE, Santa Rosa, California), which was used in 60% of cases. Intravenous aspirin and an in-lab bolus dose of heparin were routinely administered. Abciximab use was left to the discretion of the supervising physician. After the procedure, all patients received aspirin and ticlopidin for a 1-month period. All angiograms were reviewed by 2 experienced operators blinded to the results of marker determination. cTnI, CK, and CK-MB measurements: Blood samples were collected in heparinized tubes (Vacutainer, Becton Dickinson, Paris, France) 2 hours before, and then 8 and 24 hours after stent procedure and immediately sent to the laboratory. All measurements of cTnI were obtained by immunoassay on the Stratus II analyser (Dade Behring, Paris, France) using specific antibodies raised against cardiac epitopes of troponin I. Between-run coefficient of variation at approximately 0.60, 0.90 g/L was 12.3% and 6.6%, respectively. We previously described that in our institution the upper limit of normal for cTnI is 0.30 g/L.7,8 Moreover, we also measured cTnI in 20 control patients before and after catheterization. These patients had either angiographically normal coronary arteries (n ⫽ 10) or coronary artery disease, but had not undergone an interventional procedure at the time of catheterization (n ⫽ 10). Although some patients in this control group had mild cTnI changes, none was of a magnitude of ⱖ0.3 g/L. Consequently, a postprocedural
procedural creatine kinase (CK) or its MB subfraction (CK-MB) mild elevation, is associated with adverse late outcome.1,2 Nevertheless, only a few data are available concerning myocardial marker elevation after stent implantation,3 although this device is very often used in contemporary practice. Cardiac troponin I (cTnI), a regulatory contractile protein, is a very specific and sensitive marker of myocardial damage.4 It has been shown to have a prognostic value beyond CK and CK-MB in acute coronary syndromes.5,6 However, little is known about cTnI release after coronary intervention, particularly after coronary stenting. This study therefore was undertaken to prospectively evaluate the frequency, correlates, and prognostic significance of cTnI elevation after stent implantation.
METHODS
Patients: The study population consisted of 109 consecutive patients who had coronary angioplasty with concomitant stent implantation in our institution. Patients who had myocardial infarction in the previous 5 days and persistent CK elevation above the upper
From the Departments of Cardiology and Biochemistry, Tenon Hospital, Paris, France. Manuscript received January 22, 1999; revised manuscript received April 19, 1999, and accepted April 21, 1999. Address for reprints: Eric Garbarz, MD, Department of Cardiology, Tenon Hospital, 4 rue de la Chine, 75020 Paris, France. ©1999 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 84 September 1, 1999
0002-9149/99/$–see front matter PII S0002-9149(99)00369-0
515
TABLE I Angiographic Characteristics Lesion ACC/AHA classification A B1 B2 C Bifurcation lesion Vessel diameter ⬍3 mm TIMI 0 or 1 Saphenous venous graft ⬎1 vessel stented Bailout stenting Abciximab Stent length (mm) Inflation time (s)
TABLE II In-Lab Complications for the Whole Cohort 11 33 48 17 18 15 13 3 3 5 28 19 396
(10%) (30%) (44%) (16%) (17%) (14%) (12%) (3%) (3%) (4.5%) (26%) ⫾ 13 ⫾ 307
ACC/AHA ⫽ American College of Cardiology/American Heart Association; TIMI ⫽ Thrombolysis In Myocardial Infarction trial.
increase in cTnI ⱖ0.3 g/L was considered an ischemic insult. Plasma samples obtained after centrifugation were also analyzed for total CK and CK-MB by enzymatic methods (Vitros 950, Ortho Clinical Diagnostic, Roissy, France). The upper reference values for CK and CK-MB activity were 180 and 16 U, respectively, according to manufacturer’s instructions. In-hospital events: Major adverse coronary events, i.e. death, nonfatal myocardial infarction, or emergency revascularizations were recorded for the purpose of this study. Myocardial infarction was defined by the appearance of a new Q wave in at least 2 continuous leads in the electrocardiogram and/or by an elevation of CK ⱖ3 times above the upper limit of normal, with a concordant CK-MB fraction elevation (i.e., ⱖ5%). Procedural success was defined as a residual stenosis ⬍30% with a Thrombolysis In Myocardial Infarction trial grade 3 flow. Clinical success was defined as a successful procedure without inhospital major adverse coronary events. Follow-up: Inclusions ended in November 1997 and follow-up data collection was performed in June 1998 through visits at our outpatient clinic or by telephone interviews with the patients’ attending physicians. Statistical analysis: Quantitative variables are expressed as mean ⫾ SD. cTnI and CK were expressed as median (25th to 75th percentiles) due to the skewness of their distribution. Comparisons between groups used the Mann-Whitney U test for quantitative variables and the chi-square or Fisher’s exact test for qualitative variables. Comparisons of values of cTnI and CK before and after stenting used the Wilcoxon test. Univariate analysis of predictive factors determining postprocedural CK and cTnI elevation included patients’ baseline clinical and angiographic characteristics (Table I) along with in-lab complications (Table II). Analysis was performed with CSS Statistica software (Statsoft Inc., Tulsa, Oklahoma). A p value ⬍0.05 was considered significant.
RESULTS
Baseline characteristics: Mean age was 61 ⫾ 12 years (range 37 to 84). Ten patients (9%) were women. Fifty patients (46%) presented with unstable
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Occlusive dissection Thrombus No reflow Side-branch occlusion Hypotension requiring vasopressors Sustained ventricular arrhythmia
5 3 7 26 14 1
(4.5%) (3%) (6.5%) (24%) (13%) (1%)
TABLE III In-Lab Complications According to Markers Status cTnI⫹ In-Lab Complications None Side-branch occlusion No reflow Occlusive dissection Thrombus Hypotension requiring pressors Sustained ventricular arrhythmia
cTnI⫺
CK⫹ (n ⫽ 10)
CK⫺ (n ⫽ 19)
CK⫹ (n ⫽ 6)
CK⫺ (n ⫽ 74)
1 (10%) 5 (50%)
9 (47%) 5 (28%)
3 (50%) 2 (33%)
54 (73%) 14 (19%)
3 1 2 3
1 (5.6%) 2 (11%) 0 4 (22%) 1
(30%) (10%) (20%) (30%)
1 (10%)
0
0 0 0 (17%) 0
3 2 1 6
(4%) (3%) (1%) (8.2%) 0
⫹ ⫽ marker increase; ⫺ ⫽ absence of marker increase.
angina, whereas 59 (54%) underwent coronary angioplasty and stenting for stable angina and/or a positive stress test. Mean left ventricular ejection fraction was 54 ⫾ 10% (range 18% to 72%). Forty-five patients (41%) had 1-vessel disease, and 45 (41%) and 19 (18%) had 2- and 3- vessel disease, respectively. Baseline angiographic characteristics are summarized in Table I. The main reasons for stenting were: systematic in 21 patients (19%), elastic recoil in 35 (32%), nonocclusive dissection in 48 (44.5%), and bailout in 5 (4.5%). Abciximab was given to 28 patients (26%), either prophylactically in 23 (21%) or as bailout treatment in 5 (5%). Procedural outcome: Overall, the procedure was successful in 105 patients (96%). In-lab complications for the whole cohort are presented in Table II. Myocardial marker determination and correlates:
Median values of cTnI (g/L) were 0 (0 to 0) at baseline, 0 (0 to 0.9) at 8 hours (p ⫽ 0.008 vs baseline), and 0 (0 to 1.3) at 24 hours (p ⫽ 0.003 vs baseline). With regard to CK (U), the median values were: 59 (29 to 93) at baseline, 60 (37 to 112) at 8 hours (p ⫽ 0.17 vs baseline), and 69 (35 to 120) at 24 hours (p ⫽ 0.02 vs baseline). An increase in cTnI ⬎0.3 g/L at 8 and/or 24 hours was observed in 29 patients (27%). CK elevation was seen in 16 patients (15%). Only 10 patients (9%) had concordant marker elevation, whereas 19 (17%) had isolated cTnI release and 6 (5%) had CK release without cTnI elevation. The relation between in-lab complication and postprocedual marker status is detailed in Table III. Using univariate analysis, we found no preprocedural clinical or angiographic variables that predicted cTnI or CK elevation. Instead, marker release was related to the occurrence of in-lab complications: 65% of patients with an increase in cTnI had at least 1 in-lab SEPTEMBER 1, 1999
complication, whereas this was the case in only 29% of patients without cTnI elevation (p ⫽ 0.004). The respective figures for CK were 75% and 32% (p ⫽ 0.011). Total inflation time, stent length, and absence of abciximab use were not predictors of marker elevation. The occurrence of at least 1 in-lab complication was observed more frequently in patients who had release of both markers than in those who had either isolated cTnI, isolated CK, or no marker elevation; the respective values were 90%, 53%, 50%, and 27% (p ⫽ 0.001). Among patients who had an isolated increase in cTnI, 9 (47%) had no in-lab complications. In-hospital outcome: One patient died (1%) after left main retrograde dissection, 1 sustained a Q-wave myocardial infarction (1%), and 2 (2%) had a non–Qwave myocardial infarction. The 4 patients with inhospital major adverse coronary events had concordant marker release. Overall, clinical success was observed in 103 patients (94%) and was more frequent in patients who did not have postprocedural cTnI increase (100% vs 86%, p ⬍0.001). Thus, the negative predictive value of postprocedural cTnI elevation was 100%. Conversely, the positive predictive value of isolated cTnI elevation for the occurrence of in-hospital major adverse coronary events was low, only 14%. However, the positive predictive value increased to 40% in patients with concordant marker elevation. Follow-up: Follow-up was obtained in 97% of patients (mean duration 8 ⫾ 3 months). During this period of time, 2 patients (2%) died after a myocardial infarction and 8 (7%) underwent repeat coronary angioplasty. Postprocedural elevated cTnI was not a predictor of these late events.
DISCUSSION The results of this preliminary study show that cTnI elevation is common after coronary stenting and is related to the occurrence of in-lab complications. The negative predictive value of cTnI elevation for the development of in-hospital major adverse coronary events was high, whereas our results suggest that its positive predictive value seems to be low. Frequency of marker elevation: The CK elevation rate of 15% in this study is within the usually reported range between 8% and 15%.9 With regard to cardiac troponin release after coronary angioplasty, the few data available are conflicting. Cardiac troponin T release has been reported to occur between 0% and 44% after uncomplicated coronary angioplasty.10 –12 Data concerning cTnI release in a coronary angioplasty setting are even more sparse. In our series, the incidence of cTnI elevation was 27%. Hunt et al13 did not find significant cTnI elevation in a cohort of 22 patients who had a successful coronary angioplasty procedure for stable or unstable angina. Correlates of marker elevation: In studies using CK or CK-MB as markers of myocardial injuries, enzyme elevation was strongly correlated with the development of in-lab procedural complications.1,14 The other correlates were1–3,15: age, recent myocardial infarction or unstable angina, multivessel disease, complex lesions, and multivessel procedures. CK/CK-MB eleva-
tion is seen more frequently with the use of new devices, such as directional and rotational atherectomy, but the influence of stenting remains largely unknown.3 With regard to cardiac troponins release, predictors are not as well characterized. Cardiac troponin T elevation has been linked to side-branch occlusion and to inflation times.10 –12 However, in the present study the only correlate of cTnI elevation was the occurrence of in-lab complications. Finally, as was observed for CK/CK-MB,16 in 47% of cases we found no explanation for the isolated elevation of cTnI. This may be related to the clinical and experimental data that have shown that the release of a small amount of cTnI could be detected after myocardial transient ischemia without cell necrosis.17,18 Taken together, these facts could lead to the conclusion that cTnI may be an oversensitive marker in the setting of coronary angioplasty and stenting. On the other hand, this study shows that there is a high rate of in-lab complications whenever concordant marker elevation is seen. Clinical implications: The negative predictive value of cTnI elevation for in-hospital major adverse coronary events was excellent. On the other hand, our results suggest that the positive predictive value of the isolated postprocedural elevation of cTnI was low. However, the concordant elevation of both cTnI and CK/CK-MB could help to identify a small group of patients requiring particular attention after the procedure since all patients who had in-hospital major adverse coronary events were in this group. Study limitations: Our sample size is small, and therefore the possibility of a type II error is high when considering the relation between cTnI elevation and outcome. We defined a postprocedural non–Q-wave myocardial infarction as an increase in total CK ⬎3 times the upper limit of normal, with a concordant elevated CK-MB fraction. Although previous studies have used the same criteria as we have,9 a recent consensus statement3 defined procedure-related myocardial infarction as a CK-MB elevation 3 times the laboratory norm. 1. Abdelmeguid A, Topol E, Whitlow P, Sapp S, Ellis S. Significance of mild transient release of creatine kinase-MB fraction after percutaneous coronary interventions. Circulation 1996;94:1528 –1536. 2. Kong T, Davidson C, Meyers S, Tauke J, Parker M, Bonow R. Prognostic implication of creatine kinase elevation following elective coronary artery interventions. JAMA 1997;277:461– 466. 3. Califf R, Abdelmeguid A, Kuntz R, Popma J, Davidson C, Cohen E, Kleiman N, Mahaffey K, Topol E, Pepine C, Lipicky R, Granger C, Harrington R, Tardiff B, Crenshaw B, Bauman R, Zuckerman B, Chaitman B, Bittl J, Ohman M. Myonecrosis after revascularization procedures. J Am Coll Cardiol 1998;31:241– 251. 4. Coudrey L. The troponins. Arch Intern Med 1998;158:1173–1180. 5. Antman E, Tanasijevic M, Thompson B, Schactman M, McCabe C, Cannon C, Fischer G, Fung A, Thompson C, Wybenga D, Braunwald E. Cardiac-specific troponin-I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med 1996;335:1342–1349. 6. Olatidoye A, Wu A, Feng Y, Waters D. Prognostic role of troponin T versus I in unstable angina for cardiac events with meta-analysis comparing published studies. Am J Cardiol 1998;81:1405–1411. 7. Lefe`vre G, Graı¨ne H, Garbarz E, Abbas A, Vahanian A, Etienne J. Comparaisons analytique et diagnostique de deux dosages de l’isoenzyme MB de la cre´atine kinase et de deux dosages de la troponine I par me´thode immunoenzymologique. Immunoanal Biol Spe´c 1998;13:167–173. 8. Wu A, Feng Y. Biochemical differences between cTnT and cTnI and their
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significance for diagnosis of acute coronary syndromes. Eur Heart J 1998;19 (suppl N):N25–N29. 9. Abdelmeguid A, Topol E. The myth of the myocardial “infarctlet” during percutaneous coronary revascularization procedures. Circulation 1996;94:3369 – 3375. 10. Karim M, Shinn M, Oskarsson H, Windle J, Deligonul U. Significance of cardiac troponin T release after percutaneous transluminal coronary angioplasty. Am J Cardiol 1995;76:521–523. 11. Johansen O, Brekke M, Strømme JH, Valen V, Seljeflot I, Skjæggestad ø, Arnesen H. Myocardial damage during percutaneous transluminal coronary angioplasty as evidenced by troponin T measurements. Eur Heart J 1998;19:112– 117. 12. Genser N, Mair J, Friedrich G, Talasz H, Moes N, Mu¨hlberger V, Puschendorf B. Uncomplicated successful percutaneous transluminal coronary angioplasty does not affect cardiac troponin T plasma concentrations. Am J Cardiol 1996;78:127–128. 13. Hunt A, Chow S, Shiu M, Chilton D, Cummins B, Cummins P. Release of creatine kinase-MB and cardiac specific troponin-I following percutaneous transluminal coronary angioplsty. Eur Heart J 1991;12:690 – 694.
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