In summary, our findings suggest that homocysteine-lowering therapy significantly decreases restenosis rates and reduces the need for target lesion revascularization in patients undergoing PCI of small coronary arteries. 1. Elezi S, Kastrati A, Neumann FJ, Hadamitzky M, Dirschinger J, Scho¨ mig A.
Vessel size and long-term outcome after coronary stent placement. Circulation 1998;98:1875–1880. 2. Akiyama T, Moussa I, Reimers B, Ferraro M, Kobayashi Y, Blengino S, Di Francesco L, Finci L, Di Mario C, Colombo A. Angiographic and clinical outcome following coronary stenting of small vessels: a comparison with coronary stenting of large vessels. J Am Coll Cardiol 1998;32:1610 –1618. 3. Foley DP, Melkert R, Serruys PW. Influence of coronary vessel size on renarrowing process and late angiographic outcome after successful balloon angioplasty. Circulation 1994;90:1239 –1251. 4. Schnyder G, Roffi M, Pin R, Flammer Y, Lange H, Eberli FR, Meier B, Turi ZG, Hess OM. Decreased rate of coronary restenosis after lowering of plasma homocysteine levels. N Engl J Med 2001;345:1593–1600. 5. Ellis SG, Vandormael MG, Cowley MJ, DiSciascio G, Deligonul U, Topol EJ, Bulle TM. Coronary morphologic and clinical determinants of procedural outcome with angioplasty for multivessel coronary disease. Implications for patient selection. Circulation 1990;82:1193–1202. 6. Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G, Emanuelsson H, Marco J, Legrand V, Materne P, Belardi J, et al, for the Benestent Study Group. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med 1994;331:489 –495. 7. Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP, Penn I, Detre K, Veltri L, Ricci D, Nobuyoshi M, Cleman M, et al, for The Stent Restenosis Study
Investigators. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994;331: 496 –501. 8. Park SW, Lee CW, Hong MK, Kim JJ, Cho GY, Nah DY, Park SJ. Randomized comparison of coronary stenting with optimal balloon angioplasty for treatment of lesions in small coronary arteries. Eur Heart J 2000;21:1785–1789. 9. Kastrati A, Scho¨ mig A, Dirschinger J, Mehilli J, Dotzer F, von Welser N, Neumann FJ. A randomized trial comparing stenting with balloon angioplasty in small vessels in patients with symptomatic coronary artery disease. Circulation 2000;102:2593–2598. 10. Koning R, Eltchaninoff H, Commeau P, Khalife K, Gilard M, Lipiecki J, Coste P, Bedossa M, Lefe`vre T, Brunel P, et al, for the BESMART (BeStent in Small Arteries) Trial Investigators. Stent placement compared with balloon angioplasty for small coronary arteries. Circulation 2001;104:1604 –1608. 11. Doucet S, Schalij MJ, Vrolix MCM, Hilton D, Chenu P, de Bruyne B, Udayachalerm W, Seth A, Bilodeau L, Reiber JHC, Harel F, Lespe´ rance J, for the Stent In Small Arteries (SISA) Trial Investigators. Stent placement to prevent restenosis after angioplasty in small coronary arteries. Circulation 2001;104: 2029 –2033. 12. Rode´ s J, Coˆ te´ G, Lespe´ rance J, Bourassa MG, Doucet S, Bilodeau L, Bertrand OF, Harel F, Gallo R, Tardif JC. Prevention of restenosis after angioplasty in small coronary arteries with probucol. Circulation 1998;97:429 –436. 13. Vermeulen EGJ, Stehouwer CDA, Twisk JWR, van den Berg M, de Jong SC, Mackaay AJC, van Campen CMC, Visser FC, Jakobs CAJM, Bulterijs EJ, Rauwerda JA. Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebocontrolled trial. Lancet 2000;355:517–522. 14. Title LM, Cummings PM, Giddens K, Genest JJ Jr, Nassar BA. Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. J Am Coll Cardiol 2000;36:758 –765. 15. Doshi SN, McDowell IFW, Moat SJ, Lang D, Newcombe RG, Kredan MB, Lewis MJ, Goodfellow J. Folate improves endothelial function in coronary artery disease. An effect mediated by reduction of intracellular superoxide? Arterioscler Thromb Vasc Biol 2001;21:1196 –1202.
Influence of Various Percutaneous Coronary Interventional Devices on Postinterventional Luminal Shape and Plaque Surface Characteristics as Determined by Intravascular Ultrasound Berkten Berkalp, MD, Ozer Badak, MD, Paul Schoenhagen, MD, Khaled M. Ziada, Patrick L. Whitlow, MD, Steven E. Nissen, MD, and E. Murat Tuzcu, MD
MD,
he procedural success of percutaneous coronary interventions (PCIs) is routinely assessed angioT graphically by evaluating luminal dimensions and the presence or absence of dissections. The additional definitions of postinterventional characteristics of lumen geometry, lesion surface, and transmural components of atherosclerotic coronary plaques with intravascular ultrasound (IVUS) may provide important supplemental information.1,2 Using IVUS, we systematically compared these characteristics among lesions treated with different interventional devices. •••
Postinterventional IVUS examinations of 262 lesions in 256 patients were analyzed. These lesions were treated electively with isolated percutaneous transluminal coronary angioplasty (PTCA); isolated From Department of Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio. Dr. Tuzcu’s address is: The Cleveland Clinic Foundation, F25, 9500 Euclid Avenue, Cleveland Ohio 44195. E-mail:
[email protected]. Manuscript received October 4, 2002; revised manuscript received and accepted January 28, 2003. ©2003 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 91 May 15, 2003
FIGURE 1. Distribution of performed interventions. Adj ⴝ adjunctive; ROTAB ⴝ rotablation.
directional coronary atherectomy (DCA) or DCA with subsequent, adjunctive PTCA; isolated rotablation or rotablation with subsequent, adjunctive PTCA; or stent implantation between 1995 and 1998 (Figure 1). According to clinical practice during that time period, IVUS was performed for routine postintervential lesion assessment. PCI were performed in a standard manner over a 0.014-inch guidewire through 8Fr or 0002-9149/03/$–see front matter doi:10.1016/S0002-9149(03)00282-0
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groups had significantly higher frequencies of irregular lumen (36% and 23%, respectively), and the highest frequency of flap (24% and 23%, respectively) than other procedures (p ⬍0.05). Adjunctive PTCA after DCA increased the frequency of circular luminal shape and dissection, but differences in lumen shape and surface between DCA and DCA ⫹ adjunctive PTCA groups were not statistically significant (p ⫽ 0.397 and p ⫽ 0.117, respectively). Rotablation was associated with a circular luminal shape and smooth luminal surface in 69% and 62% of lesions, respectively. Although rotablation had the highest circular lumen ratio, the post-PCI lumen shape was not significantly different after FIGURE 2. Luminal shape and surface after different interventions. (A) Ellipsoid lumen; (B) circular lumen; (C) smooth circular surface after stenting; (D) superficial tear; (E) rotablation, rotablation ⫹ adjuntive flap; and (F) dissection and irregular lumen. PTCA, and PTCA and stenting. Adjunctive PTCA after rotablation increased the frequency of dissection, 10Fr guiding catheters. DCA was performed using superficial tear, and flap, and decreased the frequency atherocaths. Rotablation was performed using various of circular lumen. However, these differences were burr sizes. Balloon catheters of various manufacturers statistically insignificant (p ⫽ 0.715 for lumen shape; were used. Stents were implanted with high-pressure p ⫽ 0.284 for lumen surface). Frequency of smooth luminal surface after stenting adjunct balloon angioplasty. IVUS was performed after anticoagulation with heparin and intracoronary ad- was 84% for lesions, and significantly higher than that ministration of nitroglycerin using a 30-MHz, 3.5Fr after all other procedures (p ⬍0.002), except in the monorail ultrasound catheter (Boston Scientific rotablation group (p ⫽ 0.052 for rotablation). Surface Scimed, Maple Grove, Minnesota). Ultrasound im- damage after stenting frequently occurred at stent ages were digitized from videotape for morphometric edges. Differences in postprocedural vessel sizes are analyses (vessel area, lumen area, plaque area, and percent cross-sectional area as plaque area/vessel listed in Table 2. The lowest lumen areas were observed after rotablation (4.65 mm2). Stent, DCA, and area). Postinterventional lesion morphology was assessed DCA ⫹ adjunctive PTCA groups were similar in according to the following criterion (Figure 2): lumen lumen areas, and significantly different from PTCA, shape classified as circular or ellipsoid (symmetrically rotablation, and rotablation ⫹ adjunctive PTCA with a maximum lumen diameter ⬍30% or ⬎30% groups. DCA and stent groups also had the lowest larger than minimum diameter, respectively) or irreg- percent cross-sectional areas (56.7% and 57.4%, reular (asymmetric lumen shape). The integrity of lumi- spectively) than the PTCA and rotablation ⫹ adjuncnal surface was classified into 4 different groups: (1) tive PTCA groups (p ⫽ 0.0164). smooth luminal surface, a lumen without visible in••• terruptions; (2) superficial tear, an intimal fracture not Using IVUS, we found postinterventional characextending to the media; (3) dissection, a slit of the teristics of luminal shape and plaque surface after plaque from the lumen extending into the media; and different interventional procedures. The high fre(4) flap, separation of plaque from the vessel wall with quency of dissection after PTCA is disturbing, but has plaque fragments protruding into the lumen. Differ- been described in previous IVUS studies. The inciences in vessel morphometrics were assessed by using dence of dissections has been reported between 6% analysis of variance. Differences in luminal morphol- and 59%.1– 4 Lumen enlargement from coronary anogy between groups were compared with the chi- gioplasty occurs due to plaque compression and vessel square test. expansion. Cracks, tears, and dissections due to Characteristic morphologic changes were observed stretching of relatively inelastic components of the after different procedures (Table 1). atherosclerotic plaque allow the vessel to expand. PTCA was associated with a circular luminal shape However, angiographically visible dissections are a in 52% of lesions. The prevalence of dissection (45%) significant predictor of ischemic outcome after angiowas significantly higher than in the other groups, plasty,5 and intimal-medial disruption is a likely reexcept rotablation ⫹ adjunctive PTCA (p ⬍0.02 for sponsible mechanism for restenosis.6 According to all, but p ⫽ 0.325 for rotablation ⫹ adjunctive these observations, a balance may exist between some PTCA). The DCA and DCA ⫹ adjunctive PTCA degree of dissection necessary for a successful PTCA 1270 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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TABLE 1 Luminal Shape and Surface Characteristics After Different Interventions
Luminal shape Circular Ellipsoid Irregular Luminal surface Dissection Superficial Tear Flap Smooth
PTCA (n ⫽ 65)
DCA (n ⫽ 58)
DCA ⫹ Adj PTCA (n ⫽ 35)
Rotab. (n ⫽ 39)
Rotab ⫹ Adj. PTCA (n ⫽ 31)
Stent (n ⫽ 70)
52.3 (34) 43.1 (28) 4.6 (3)
36.2 (21) 27.6 (16) 36.2 (21)
45.8 (16) 31.4 (11) 22.8 (8)
69.2 (27) 28.2 (11) 2.6 (1)
64.5 (20) 29.0 (9) 6.5 (2)
62.9 (44) 32.8 (23) 4.3 (3)
44.6 (29)
17.2 (10)
20.0 (7)
23.0 (9)
25.8 (8)
20.0 (13) 3.1 (2) 32.3 (21)
12.1 (7) 24.1 (14) 46.6 (27)
11.5 (4) 22.8 (8) 45.7 (16)
12.8 (5) 2.6 (1) 61.6 (24)
22.6 (7) 9.7 (3) 41.9 (13)
7.1 (5) 7.1 (5) 1.4 (1) 84.4 (59)
Percent values are given without parentheses. Values within parentheses are the number of lesions. Adj. ⫽ adjunct; Rotab. ⫽ rotablation.
TABLE 2 Morphometric Parameters After Different Interventions
Vessel area (mm2) Lumen CSA (mm2) % CSA
PTCA (n ⫽ 65)
DCA (n ⫽ 58)
DCA ⫹ Adj PTCA (n ⫽ 35)
Rotab (n ⫽ 39)
Rotab ⫹ Adj PTCA (n ⫽ 31)
Stent (n ⫽ 70)
13.8 ⫾ 4.4 5.0 ⫾ 2.0 62.1 ⫾ 1.4
17.9 ⫾ 6.1 7.4 ⫾ 2.5 56.7 ⫾ 1.4
19.9 ⫾ 4.9 8.0 ⫾ 2.2 58.9 ⫾ 1.1
12.6 ⫾ 3.2 4.7 ⫾ 1.7 61.3 ⫾ 1.2
15.4 ⫾ 5.7 5.1 ⫾ 2.0 65.5 ⫾ 0.9
17.6 ⫾ 5.3 7.3 ⫾ 2.6 57.4 ⫾ 1.1
Data are expressed as mean value ⫾ SD. CSA ⫽ cross-sectional area; other abbreviations as in Table 1.
procedure and overt dissection increasing the risk of adverse clinical outcomes. The characteristic finding after rotational atherectomy was a circular lumen and smooth surface. Rotational atherectomy abrades occlusive atherosclerotic, especially noncompliant, calcified plaque. Deviations from cylindrical geometry occur only in areas of soft plaque or superficial tissue disruption of calcified plaque.7 Fissures and dissections were uncommon. Dissections were seen in only 23%, and were superficial, located within an arch of calcified plaque, and had limited extension. Rotational atherectomy caused lumen enlargement, with little tissue disruption and minimal arterial expansion. Luminal shape and surface after DCA showed a wide variety of findings. The high percentage of smooth luminal surface is surprising. During DCA, the vessel stretches because of balloon inflation, but discrete bites, corresponding to passes of the cutting blade, should be expected to cause irregular lumen shape. However, other studies using IVUS imaging have also reported a small percentage of dissections after atherectomy.8,9 Intimal disruptions at uncovered vessel sites after stent implantation have been reported to occur in 13% to 30% of lesions and are mainly located at stent edges.10,11 We found that 19% of the stented lesions had varying degrees of intimal damage that were angiographically inapparent. However, the clinical significance of angiographically silent edge dissections is unclear.12–15 A circular lumen shape was reported to be a key factor for long-term outcome.16 Luminal shape after stenting was circular in 63% of the lesions in this trial. Restoration of a circular luminal shape may optimize flow dynamics on the intimal
surface by leading to more laminar flow within the lumen. It is well known that postprocedural luminal size is the most important factor affecting restenosis. We found differences in postprocedural lumen size similar to recent reports.17,18 Lesions after DCA and stenting had larger luminal areas and lower percent cross-sectional areas than lesions after PTCA and rotablation compared with other procedures. However, because of the lack of preprocedural IVUS measurements, we cannot exclude the possibility that device selection was influenced by vessel size in our study. We examined luminal geometry, lesion surface, and transmural characteristics of atherosclerotic plaque after various types of PCIs using IVUS. Characteristic differences in postprocedural lesion morphology were found between different device strategies. 1. Davidson CJ, Sheikh KH, Kisslo KB, Phillips HR, Peter RH, Behar VS, Kong
Y, Krucoff M, Ohman EM, Tcheng JE, Stack RS. Intracoronary ultrasound evaluation of interventional technologies. Am J Cardiol 1991;68:1305–1309. 2. Honye J, Mahon DJ, Jain A, White CJ, Ramee SR, Wallis JB, Al-Zarka A, Tobis JM. Morphological effects of coronary balloon angioplasty in vivo assessed by intravascular ultrasound imaging. Circulation 1992;85:1012–1025. 3. Gerber TC, Erbel R, Gorge G, Ge J, Rupprecht HJ, Meyer J. Classification of morphologic effects of percutaneous transluminal coronary angioplasty assessed by intravascular ultrasound. Am J Cardiol 1992;70:1546 –1554. 4. Braden GA, Herrington DM, Downes TR, Kutcher MA, Little WC. Qualitative and quantitative contrasts in the mechanisms of lumen enlargement by coronary balloon angioplasty and directional coronary atherectomy. J Am Coll Cardiol 1994;23:40 –48. 5. Ellis SG, Roubin GS King SB III,, Douglas JS Jr, Weintraub WS, Thomas RG, Cox WR. Angiographic and clinical predictors of acute closure after native vessel coronary angioplasty. Circulation 1988;77:372–379. 6. Nobuyoshi M, Kimura T, Nosaka H, Mioka S, Ueno K, Yokoi H, Hamasaki N,
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Horiuchi H, Ohishi H. Restenosis after successful percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 1988;12:616 –623. 7. Mintz GS, Potkin BN, Keren G, Satler LF, Pichard AD, Kent KM, Popma JJ, Leon MB. Intravascular ultrasound evaluation of the effect of rotational atherectomy in obstructive atherosclerotic coronary artery disease. Circulation 1992;86: 1383–1393. 8. Penny WF, Schmidt DA, Safian RD, Erny RE, Baim DS. Insights into the mechanism of luminal improvement after directional coronary atherectomy. Am J Cardiol 1991;67:435–437. 9. Hardt SE, Bekeredjian R, Brachmann J, Kuecherer HF, Hansen A, Kubler W, Katus HA. Intravascular ultrasound for evaluation of initial vessel patency and early outcome following directional coronary atherectomy. Cathet Cardiovasc Intervent 1999;47:14 –22. 10. Honda Y, Yock PG, Fitzgerald PJ. Impact of residual burden on clinical outcomes of coronary interventions. Cathet Cardiovasc Intervent 1999;46:265– 276. 11. Schwarzacher SP, Metz JA, Yock PG, Fitzgerald PJ. Vessel tearing at the edge of intracoronary stents detected with intravascular ultrasound imaging. Cathet Cardiovasc Diagn 1997;40:152–155. 12. Uren NG, Schwarzacher SP, Metz JA, Lee DP, Honda Y, Yeung AC, Fitzgerald PJ, Yock PG. Predictors and outcomes of stent thrombosis. An intravascular ultrasound registry. Eur Heart J 2002;23:124 –132.
13. Hoffman R. Mintz GS, Popma JJ, Pichard AD, Satler LF, Kent KM, Griffin J, Bucher T, Fuessl R, Kenoe MK, et al. What causes focal restenosis at the margins of Palmaz-Schatz stents? A serial intravascular ultrasound study (abstr). J Am Coll Cardiol 1996;27:321A. 14. Hong MK, Park SW, Lee NH, Nah DY, Lee CW, Kang DH, Song JK, Kim JJ, Park SJ. Long-term outcomes of minor dissection at the edge of stents detected with intravascular ultrasound. Am J Cardiol 2000;86:791–795. 15. Sheris SJ, Canos MR, Weismann NJ. Natural history of intravascular ultrasound-detected edge dissections from coronary stent deployment. Am Heart J 2000;139:59 –63. 16. Garasic JM, Edelman ER, Squire JC, Seifert P, Williams MS, Rogers C. Stent and artery geometry determine intimal thickening independent of arterial injury. Circulation 2000;101:812–818. 17. Tsuchikane E, Sumitsuji S, Awata N, Nakamura T, Kobayashi T, Izumi M, Otsuji S, Tateyama H, Sakurai M, Kobayashi T. Final Results of the STent versus directional coronary Atherectomy Randomized Trial (START). J Am Coll Cardiol 1999;34:1050 –1057. 18. Simonton CA, Leon MB, Baim DS, Hinohara T, Kent KM, Bersin RM Wilson ⫹BH,, Mintz GS, Fitzgerald PJ, Yock PG, et al. “Optimal” directional coronary atherectomy: final results of the Optimal Atherectomy Restenosis Study (OARS). Circulation 1998;97:332–339.
Prognostic Implication of Troponin I Elevation After Percutaneous Coronary Intervention Brahmajee K. Nallamothu, MD, MPH, Stanley Chetcuti, MD, Debabrata Mukherjee, P. Michael Grossman, MD, Eva Kline-Rogers, RN, Steven W. Werns, MD, Eric R. Bates, MD, and Mauro Moscucci, MD arge elevations in creatine phosphokinase (CPK)MB levels after percutaneous coronary intervenL tion (PCI) are associated with decreased long-term survival.1–10 However, results from similar studies using troponin I—a more sensitive and specific biomarker for detecting myocardial infarction (MI)11— have been inconclusive.12–15 Accordingly, we assessed the impact of troponin I elevation on long-term survival in a large registry of patients who underwent nonemergency PCI at a tertiary-care academic medical center. •••
We identified 2,796 consecutive cases of PCI performed at a tertiary-care referral center between July 1, 1997, and October 31, 2001. Excluded from the analysis were 407 repeat PCIs in previously indexed patients (i.e., index cases alone were included), and 1,026 PCIs performed under (1) emergency conditions (e.g., hemodynamic instability) or (2) within 7 days of an MI (including all patients with baseline troponin I elevations). In addition, troponin I levels—routinely measured in patients undergoing PCI at our institution since 1997—were unavailable in 206 cases. Thus, 1,157 cases were available for final analysis. PCI included stents (77.3%), balloon angioplasty alone (19.8%), directional or rotational atherectomy (5.6%), rheolytic thrombectomy (0.3%), and cutting-balloon From the Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan. Dr. Moscucci’s address is: Taubman Center 3910, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-0366. E-mail:
[email protected]. Manuscript received November 19, 2002; revised manuscript received and accepted January 28, 2003.
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MD,
angioplasty (0.3%). (Note that numbers do not add up to 100% owing to overlap between groups.) Data collection was approved by an institutional review board. Clinical, procedural, and in-hospital outcome data were collected prospectively by trained abstractors using a standardized form.16 Data accuracy was ensured by random auditing and by reviewing records for all in-hospital deaths and bypass graft surgeries. Follow-up data on survival were available in all cases. In 960 patients (82.9%), data were collected using direct telephone contact. In remaining patients, the US Social Security Death Index was searched to determine vital status as of February 2002. For all patients, troponin I levels were obtained at baseline and at least once 6 to 24 hours after PCI. Additional levels during hospitalization were ordered at the discretion of the clinical service. When multiple levels were available, we used the peak troponin I level for our analysis. Troponin I levels were measured using the AxSYM Troponin I assay (Abbott Laboratories, Abbott Park, Illinois). Using groupings similar to those in previous studies of CPK-MB release after PCI,1 patients were stratified prospectively based on their peak post-PCI troponin I level into 5 categories: normal (⬍2.0 ng/ml); 1 to ⬍3 ⫻ normal; 3 to ⬍5 ⫻ normal, 5 to ⬍8 ⫻ normal; and ⱖ8 ⫻ normal. In 314 patients (27.1%), left ventricular ejection fraction data were missing and therefore imputed using a linear regression model that included age, gender, left ventricular end-diastolic pressure, and history of congestive heart failure, bypass surgery, or MI.16 Multivariate logistic regression was used to identify predictors of large troponin I elevation (ⱖ8 ⫻ 0002-9149/03/$–see front matter doi:10.1016/S0002-9149(03)00283-2
