CLINICAL RESEARCH
Prediction of Left Ventricular Function After Drug-Eluting Stent Implantation for Chronic Total Coronary Occlusions
Timo Baks, MD*, ,
Robert-Jan van Geuns, MD, PhD*,,
Dirk J. Duncker, MD, PhD*,
Filippo Cademartiri, MD*,,
Nico R. Mollet, MD*,,
Gabriel P. Krestin, MD, PhD,
Patrick W. Serruys, MD, PhD, FACC* and
Pim J. de Feyter, MD, PhD, FACC*,,*
* Department of Cardiology, Thoraxcenter
Department of Radiology, Erasmus Medical Center, Rotterdam, the Netherlands
Manuscript received June 13, 2005;
revised manuscript received October 14, 2005,
accepted October 17, 2005.
* Reprint requests and correspondence: Dr. Pim J. de Feyter, Erasmus Medical Center, Department of Cardiology and Radiology, Thorax Center, Room Ba 591, Dr. Molewaterplein 40, 3000 GD Rotterdam, the Netherlands (Email: p.j.defeyter{at}erasmusmc.nl).
 |
Abstract
|
|---|
OBJECTIVES: We studied the effect of drug-eluting stent implantation for chronic total coronary occlusion (CTO) on left ventricular volumes and function and assessed the predictive value of magnetic resonance imaging (MRI) performed before revascularization.
BACKGROUND: The effect of recanalization of CTO on long-term left ventricular function and the value of myocardial viability assessment with MRI is incompletely understood.
METHODS: Twenty-seven patients underwent contrast-enhanced MRI before and five months after successful drug-eluting stent implantation for CTO. A CTO was defined as a complete occlusion of a major epicardial coronary artery existing for at least six weeks (mean, 7 ± 5 months). Myocardial wall thickening and left ventricular volumes were quantified on cine-images, and the transmural extent of infarction (TEI) was scored on delayed-enhancement images.
RESULTS: A significant decrease in mean end-systolic volume index (34 ± 13 ml/m2 to 31 ± 13 ml/m2; p = 0.02) and mean end-diastolic volume index (84 ± 15 ml/m2 to 79 ± 15 ml/m2; p < 0.002) was observed, whereas the mean ejection fraction did not change significantly (61 ± 9% to 62 ± 11%; p = 0.54). The extent of the left ventricle that was dysfunctional but viable before revascularization was related to improvement in end-systolic volume index (R = 0.46; p = 0.01) and ejection fraction (R = 0.49; p = 0.01) but not to the end-diastolic volume index (R = 0.10; p = 0.53). Segmental wall thickening improved significantly in segments with <25% TEI (21 ± 15% to 35 ± 25%; p < 0.001), tended to improve in segments with 25% to 75% TEI (18 ± 22% to 27 ± 22%; p = 0.10), whereas segments with >75% TEI did not improve (4 ± 14% to –9 ± 14%; p = 0.54).
CONCLUSIONS: Drug-eluting stent implantation for a CTO has a beneficial effect on left ventricular volumes and function that can be predicted by performing MRI before revascularization.
Chronic total coronary occlusions (CTO) are observed in 35% to 50% of patients with significant coronary disease undergoing diagnostic angiography (1,2). Percutaneous coronary intervention (PCI) for CTO is increasingly used as treatment strategy and accounts for 10% to 15% of all angioplasties. New catheter-based techniques have led to higher success rates of PCI (3), and drug-eluting stents significantly reduce the incidence of restenosis and re-occlusion (4). However, the effect of PCI on myocardial contractility and left ventricular volumes of the individual patient with CTO is incompletely understood. Previous studies used left ventricular angiography to study left ventricular function and volumes after balloon angioplasty or bare-metal stents for CTO, but results have been equivocal (5–7). These equivocal results may partly be caused by the rather crude measurements offered by left ventricular angiography in conjunction with the high restenosis and reocclusion rate after balloon angioplasty or bare-metal stent implantation. The use of contrast-enhanced magnetic resonance imaging (ce-MRI) permits refined assessment of myocardial contractility, left ventricular volumes, and the transmural extent of infarction (TEI) (8). We used ce-MRI to study the effect of drug-eluting stent implantation for CTO on left ventricular volumes and function and to evaluate the diagnostic value of ce-MRI to predict improvement in regional and global left ventricular function.
|
Methods
|
|---|
Patient population.
Patients scheduled for percutaneous revascularization of a CTO of a native coronary artery and without contraindications for MRI were prospectively selected for enrollment in this study. Of 50 selected patients, 3 patients refused to participate, 47 patients underwent MRI at 16 ± 16 days before PCI, and 27 patients underwent follow-up MRI at 5 ± 1 months after PCI. Twenty patients did not undergo follow-up MRI; in 13 patients, PCI was not successful, 1 patient gained too much weight to fit into the scanner, 1 patient had a defibrillator implanted, and 5 patients refused re-investigation. All procedures were performed by operators highly experienced in the treatment of CTO, with the interventional strategy left to the discretion of the operator. All participants gave written informed consent to the study protocol, which was approved by the medical ethics committee of the Erasmus Medical Center, Rotterdam. More patient characteristics are listed in Table 1.
MRI protocol.
A 1.5-T MRI scanner with a dedicated four-element phased-array receiver coil was used for imaging (Signa CV/i, GE Medical Systems, Milwaukee, Wisconsin). Cine-MRI was performed at baseline and follow-up with a steady-state free-precession technique. Sequence details have been published (9). To cover the entire left ventricle, 9 to 12 consecutive slices of 8 mm in the short-axis view were planned on the four chambers (gap of 2 mm). Delayed enhancement imaging was performed at the baseline scan 10 to 20 min after administration of gadolinium-diethyltriaminepentaacetic acid (0.1 mmol/kg intravenously, Magnevist, Schering, Germany). A two-dimensional T1-weighted inversion recovery gradient-echo sequence was used as described previously (9). The inversion time was adjusted per patient to null the signal of remote myocardium. Slice locations were copied from the locations of the cine-images.
Definitions and data analysis.
All conventional angiograms before revascularization were evaluated by two experienced observers (Drs. Baks and van Geuns). Collateral function was scored on a four-point scale (10). The CTO was defined as a complete occlusion of a major coronary artery existing for at least six weeks as obtained from either the date from the previous angiogram or the clinical history of prolonged anginal chest pain or myocardial infarction. Left ventricular volumes and mass were quantified using a dedicated software package (Mass, Medis, the Netherlands). Papillary muscles were considered as part of the left ventricular volume. Regional analysis per patient was assessed using a 16-segment model excluding the apex (11). Segmental wall thickening (SWT) was calculated by (end-systolic – end-diastolic wall thickness)/end-diastolic wall thickness x 100%. Myocardial segments were considered dysfunctional if SWT was 45% or less (12). To study the effect of revascularization on SWT, segments in the perfusion territory of a CTO (defined on conventional angiogram) were analyzed for wall thickening at baseline and at five months.
Two investigators (Drs. Baks and van Geuns), blinded for the clinical data, analyzed delayed enhancement images for the TEI, and the decision was made on the basis of consensus. The TEI was calculated by dividing the hyper-enhanced area by the total area in 16 segments per patient as: 1 = 0% (TEI), 2 = 1% to 25%, 3 = 26% to 50%, 4 = 51% to 75%, 5 = 76% to 100%. A myocardial segment with a 0% to 25% TEI was considered viable (13). The percentage of dysfunctional but viable myocardium per patient was calculated by dividing the sum of all dysfunctional but viable segments by the total amount of segments.
Statistical analysis.
Data are presented as mean ± standard deviation. Two-way analysis of variance with repeated measures over time followed by Bonferroni correction (four groups) was used to compare changes in SWT in viable segments (<25% TEI), possible viable segments (26% to 75% TEI), non-viable segments (>75% TEI), and remote segments between baseline and follow-up and to evaluate differences in SWT at baseline and at follow-up. The change in left ventricular volume indexes was tested with paired Student t tests. The relationship between the viability score per patient and the change in left ventricular volumes was analyzed with univariate linear regression analysis. All tests were performed two-sided, and significance was accepted at a p value of  0.05.
|
Results
|
|---|
Patient population.
The CTO was located in the left anterior descending coronary artery in 14 patients, in the right coronary artery in 10 patients, and in the circumflex coronary artery in 3 patients. The mean duration of occlusion was 7 ± 5 months. The overall mean procedural time was approximately 143 ± 62 min. A total of 432 segments were available for analysis, and no segments had to be excluded because of image quality.
Left ventricular function and volumes.
Mean end-systolic volume index decreased significantly from 34 ± 13 ml/m2 to 31 ± 13 ml/m2 (p = 0.02; 66 ± 29 ml to 60 ± 28 ml, p = 0.02), and mean end-diastolic volume index decreased significantly from 84 ± 15 ml/m2 to 79 ± 15 ml/m2 (p < 0.002; 162 ± 38 ml to 153 ± 36 ml, p = 0.002). Overall mean ejection fraction remained unchanged from 61 ± 9% to 62 ± 11% (p = 0.54) (Fig. 1). The extent of the left ventricle that was dysfunctional but viable before revascularization was related to improvement in end-systolic volume index (R = 0.46; p = 0.01) and ejection fraction (R = 0.49; p = 0.01) but not to the end-diastolic volume index (R = 0.10; p = 0.53) (Fig. 2).
View larger version (11K):
[in this window]
[in a new window]
|
Figure 1 The change in left ventricular volume indexes between baseline and five months of follow-up measured with magnetic resonance imaging (MRI). The mean ejection fraction remained unchanged, but end-systolic and end-diastolic volume index decreased significantly.
|
|
View larger version (10K):
[in this window]
[in a new window]
|
Figure 2 Improvement in end-systolic volume index (ESVI) and ejection fraction (EF) was related to the extent of dysfunctional but viable myocardium before revascularization. No relationship was found for end-diastolic volume index (EDVI).
|
|
In dysfunctional but viable segments (<25% TEI), mean SWT improved significantly from 21 ± 15% to 35 ± 25% (p < 0.001), whereas mean SWT tended to improve from 18 ± 22% to 27 ± 22% (p = 0.10) in segments with 25% to 75% TEI and did not improve (4 ± 14% to –9 ± 14%; p = 0.54) in segments with >75% TEI (Fig. 3). Improvement of more than 10% in absolute SWT was observed in 76% of dysfunctional segments (16 of 21) with TEI 0%, in 67% (4 of 6) with TEI 1% to 25%, 35% (6 of 17) with TEI 26% to 50%, 35% (5 of 14) with TEI 51% to 75%, and 0% (0 of 4) with TEI >75%. The sensitivity, specificity, and positive and negative predictive values of MRI for predicting segmental improvement were 65% (20 of 31), 77% (24 of 31), 74% (20 of 27), and 69% (24 of 35), respectively, using <25% TEI as the threshold for viability. Left ventricular mass index did not change significantly from 64 ± 13 g/m2 to 63 ± 11 g/m2 (p = 0.25; 127 ± 27 g to 122 ± 22 g, p = 0.26).
View larger version (12K):
[in this window]
[in a new window]
|
Figure 3 Improvement in segmental wall thickening (SWT) was related to the transmural extent of infarction assessed with magnetic resonance imaging (MRI) before revascularization. Solid bars = before revascularization; open bars = five months after revascularization.
|
|
|
Discussion
|
|---|
We showed the beneficial effect of successful drug-eluting stent implantation for CTO on end-systolic and end-diastolic volumes and SWT. Furthermore, we showed that the extent of dysfunctional but viable myocardium before revascularization was related to improvement in end-systolic volume, ejection fraction, and SWT.
Previous studies investigated the effect of successful PCI for CTO on left ventricular function (5,14–18). Overall, the average of left ventricular improvement is not overwhelming and is likely to escape detection by crude measurements of global left ventricular ejection fraction, and seems to be limited to fairly recent occlusions. In the current study, we used up-to-date methodology to study a well-defined group of patients with a duration of occlusion of more than six weeks and well-developed collaterals making PCI feasible. All patients received a drug-eluting stent with reported low restenosis/reocclusion rates, and all patients underwent MRI before and after PCI, permitting refined assessment of left ventricular volumes and myocardial viability. The magnitude of change observed in global left ventricular indexes was relatively small but in line with previously reported data on patients studied after myocardial infarction (19,20).
In the present study, ce-MRI predicted 74% of dysfunctional but viable segments correctly for showing improvement in function after revascularization. The remaining 26% of segments did not improve, although >75% of the wall consisted of viable myocardium as defined by ce-MRI. Experimental studies showed that ce-MRI can accurately differentiate viable myocardium from scarred myocardium in dogs eight weeks after reperfused infarction (8). However, viable myocardium in patients with chronic ischemic heart disease might undergo changes determined by the severity of the coronary artery stenosis, the duration and frequency of limited flow to the myocardium, and the quality of myocardial perfusion at rest. Myocardial biopsies in patients with chronic myocardial ischemia showed signs of atrophy and degeneration in chronic ischemic but predominantly viable myocardium (21). These microscopic changes of ischemic myocardium are not depicted with currently available imaging techniques, but might explain the variation observed in the reversibility of dysfunctional but viable myocardium as defined by ce-MRI. Additional techniques such as dobutamine stress MRI performed before revascularization might identify reversible dysfunctional myocardium better than ce-MRI because it allows a direct assessment of the contractile reserve of dysfunctional myocardium (22). However, a lack of functional improvement does not preclude a beneficial effect of restoring blood flow to dysfunctional but predominantly viable myocardium. In the present study, restoring blood flow to dysfunctional but viable myocardium led to a moderate improvement in function and a reduction in adverse remodeling in a majority of patients with a CTO, but other beneficial effects such as prevention of arrhythmias and prevention of recurrent myocardial ischemia were not assessed.
Study limitations.
Angiography at follow-up was not performed, but no clinical evidence of recurrent myocardial ischemia was noted and all patients received a drug-eluting stent with very low numbers of restenosis reported (4). The definition for CTO was arbitrarily set at six weeks in the present study, whereas previous studies defined CTO as seven days until three months of occlusion time. Delayed enhancement patterns at follow-up were not studied, but might provide further insight in the pathophysiological mechanisms underlying recovery of function of viable myocardium.
|
Conclusions
|
|---|
Implantation of a drug-eluting stent in patients with a CTO has a beneficial effect on myocardial contractility and left ventricular volumes. Improvement in regional and global left ventricular function after revascularization is related to the extent of dysfunctional but viable myocardium assessed with MRI before revascularization.
|
References
|
|---|
1. Christofferson RD, Lehmann KG, Martin GV, Every N, Caldwell JH, Kapadia SR. Effect of chronic total coronary occlusion on treatment strategy Am J Cardiol 2005;95:1088-1091.[CrossRef][Web of Science][Medline]2. Kahn JK. Angiographic suitability for catheter revascularization of total coronary occlusions in patients from a community hospital setting Am Heart J 1993;126:561-564.[CrossRef][Web of Science][Medline] 3. Suero JA, Marso SP, Jones PG, et al. Procedural outcomes and long-term survival among patients undergoing percutaneous coronary intervention of a chronic total occlusion in native coronary arteries: a 20-year experience J Am Coll Cardiol 2001;38:409-414.[Abstract/Free Full Text] 4. Hoye A, Tanabe K, Lemos PA, et al. Significant reduction in restenosis after the use of sirolimus-eluting stents in the treatment of chronic total occlusions J Am Coll Cardiol 2004;43:1954-1958.[Abstract/Free Full Text] 5. Sirnes PA, Myreng Y, Molstad P, Bonarjee V, Golf S. Improvement in left ventricular ejection fraction and wall motion after successful recanalization of chronic coronary occlusions Eur Heart J 1998;19:273-281.[Abstract/Free Full Text] 6. Danchin N, Angioi M, Cador R, et al. Effect of late percutaneous angioplastic recanalization of total coronary artery occlusion on left ventricular remodeling, ejection fraction, and regional wall motion Am J Cardiol 1996;78:729-735.[CrossRef][Web of Science][Medline] 7. Van Belle E, Blouard P, McFadden EP, Lablanche JM, Bauters C, Bertrand ME. Effects of stenting of recent or chronic coronary occlusions on late vessel patency and left ventricular function Am J Cardiol 1997;80:1150-1154.[CrossRef][Web of Science][Medline] 8. Kim RJ, Fieno DS, Parrish TB, et al. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function Circulation 1999;100:1992-2002.[Abstract/Free Full Text] 9. Baks T, van Geuns RJ, Biagini E, et al. Recovery of left ventricular function after primary angioplasty for acute myocardial infarction Eur Heart J 2005;26:1070-1077.[Abstract/Free Full Text] 10. Rentrop KP, Cohen M, Blanke H, Phillips RA. Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects J Am Coll Cardiol 1985;5:587-592.[Abstract] 11. Cerqueira MD, Weissman NJ, Dilsizian V, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association Circulation 2002;105:539-542.[Free Full Text] 12. Holman ER, Buller VG, de Roos A, et al. Detection and quantification of dysfunctional myocardium by magnetic resonance imagingA new three-dimensional method for quantitative wall-thickening analysis. Circulation 1997;95:924-931.[Abstract/Free Full Text] 13. Kim RJ, Wu E, Rafael A, et al. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction N Engl J Med 2000;343:1445-1453.[Abstract/Free Full Text] 14. Dzavik V, Carere RG, Mancini GB, et al. Predictors of improvement in left ventricular function after percutaneous revascularization of occluded coronary arteries: a report from the Total Occlusion Study of Canada (TOSCA) Am Heart J 2001;142:301-308.[CrossRef][Web of Science][Medline] 15. Singh A, Murray RG, Chandler S, Shiu MF. Myocardial salvage following elective angioplasty for total coronary occlusion Cardiology 1987;74:474-478.[Web of Science][Medline] 16. Pfisterer ME, Buser P, Osswald S, Weiss P, Bremerich J, Burkart F. Time dependence of left ventricular recovery after delayed recanalization of an occluded infarct-related coronary artery: findings of a pilot study J Am Coll Cardiol 1998;32:97-102.[Abstract/Free Full Text] 17. Melchior JP, Doriot PA, Chatelain P, et al. Improvement of left ventricular contraction and relaxation synchronism after recanalization of chronic total coronary occlusion by angioplasty J Am Coll Cardiol 1987;9:763-768.[Abstract] 18. Bellenger NG, Yousef Z, Rajappan K, Marber MS, Pennell DJ. Infarct zone viability influences ventricular remodeling after late recanalisation of an occluded infarct related artery Heart 2005;91:478-483.[Abstract/Free Full Text] 19. Pfeffer MA, Lamas GA, Vaughan DE, Parisi AF, Braunwald E. Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction N Engl J Med 1988;319:80-86.[Abstract] 20. Mitchell GF, Lamas GA, Vaughan DE, Pfeffer MA. Left ventricular remodeling in the year after first anterior myocardial infarction: a quantitative analysis of contractile segment lengths and ventricular shape J Am Coll Cardiol 1992;19:1136-1144.[Abstract] 21. Canty Jr. JM, Fallavollita JA. Hibernating myocardium J Nucl Cardiol 2005;12:104-119.[CrossRef][Web of Science][Medline] 22. Wellnhofer E, Olariu A, Klein C, et al. Magnetic resonance low-dose dobutamine test is superior to SCAR quantification for the prediction of functional recovery Circulation 2004;109:2172-2174.[Abstract/Free Full Text]
This article has been cited by other articles:
|
|
|
|
 
J. A. Grantham, S. P. Marso, J. Spertus, J. House, D. R. Holmes Jr, and B. D. Rutherford
Chronic Total Occlusion Angioplasty in the United States
J. Am. Coll. Cardiol. Intv.,
June 1, 2009;
2(6):
479 - 486.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Klein, E. Nagel, R. Gebker, S. Kelle, B. Schnackenburg, K. Graf, S. Dreysse, and E. Fleck
Magnetic Resonance Adenosine Perfusion Imaging in Patients After Coronary Artery Bypass Graft Surgery
J. Am. Coll. Cardiol. Img.,
April 1, 2009;
2(4):
437 - 445.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W P Bandettini and A E Arai
Advances in clinical applications of cardiovascular magnetic resonance imaging
Heart,
November 1, 2008;
94(11):
1485 - 1495.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. K. Courtney, N. R. Munce, K. J. Anderson, A. S. Thind, G. Leung, P. E. Radau, F. S. Foster, I. A. Vitkin, R. S. Schwartz, A. J. Dick, et al.
Innovations in imaging for chronic total occlusions: a glimpse into the future of angiography's blind-spot
Eur. Heart J.,
March 1, 2008;
29(5):
583 - 593.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S.H. Cheng, J. B. Selvanayagam, M. Jerosch-Herold, W. J. van Gaal, T. D. Karamitsos, S. Neubauer, and A. P. Banning
Percutaneous treatment of chronic total coronary occlusions improves regional hyperemic myocardial blood flow and contractility insights from quantitative cardiovascular magnetic resonance imaging.
J. Am. Coll. Cardiol. Intv.,
February 1, 2008;
1(1):
44 - 53.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. W.J.C. Serruys and R.-J. van Geuns
Arguments for recanalization of chronic total occlusions.
J. Am. Coll. Cardiol. Intv.,
February 1, 2008;
1(1):
54 - 55.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. S Werner
Collaterals: how important are they?
Heart,
July 1, 2007;
93(7):
778 - 779.
[Full Text]
[PDF]
|
|
|
|
Top
Abstract
Methods