Author + information
- Received February 1, 1999
- Revision received August 24, 1999
- Accepted October 25, 1999
- Published online February 1, 2000.
- Balram Bhargava, MD, DMa,
- Ran Kornowski, MD, FACCa,* (, )
- Roxana Mehran, MD, FACCa,
- Kenneth M Kent, MD, PhD, FACCa,
- Mun K Hong, MD, FACCa,
- Alexandra J Lansky, MD, FACCa,
- Ron Waksman, MD, FACCa,
- Augusto D Pichard, MD, FACCa,
- Lowell F Satler, MD, FACCa and
- Martin B Leon, MD, FACCa
- ↵*Reprint requests and correspondence: Dr. Ran Kornowski, Cardiology Research Foundation, Washington Cardiology Center, Suite 4B-1, 110 Irving Street NW, Washington, DC 20010
This study was also presented at the 48th Scientific Sessions of the American College of Cardiology, New Orleans, Louisiana, March 1999.
We evaluated the early and mid-term (18-month) clinical events in a consecutive series of patients undergoing a nonstaged multiple saphenous vein grafting (SVG) intervention with stents as compared with a single SVG stent procedure.
Saphenous vein graft angioplasty has been limited by high rates of distal embolization, myocardial infarction, restenosis and late mortality. It is unknown whether stenting of multiple, different SVGs at the same setting is associated with higher risk.
We evaluated in-hospital and mid-term clinical outcomes (death, Q wave myocardial infarction [MI] and repeat revascularization rates up to 18 months) in 70 consecutive patients treated with coronary stents in 2 (93% of patients) or 3 SVGs, as compared with 649 patients undergoing stenting of a single SVG between January 1, 1994 and December 31, 1997.
Overall procedural success was obtained in 97% of patients with 2 or 3 SVGs and 97% of patients with a single SVG (p = 0.94). Procedural complications were also similar (2.8% for multiple SVGs vs. 2.7% for a single SVG, p = 0.94). There was a higher prevalence of periprocedural non–Q wave MI (28% vs. 16%, p = 0.009) in the multiple SVG group. During follow-up (18 months), target lesion revascularization was 11% in multiple SVG and 15% in single SVG interventions (p = 0.19), and repeat revascularization (calculated per treated patient) was also similar for both groups (19% vs. 18%, p = 0.94). There was no difference in death (5.6% vs. 5.3%, p = 0.92) and Q wave MI rate (4.3% vs. 2.9%, p = 0.55) after the multiple SVG intervention. Overall cardiac event-free survival was similar for both groups (62% vs. 60%, p = 0.75). The study was powered to detect a clinically meaningful difference of 10% in mortality; smaller differences could not be evaluated on the basis of this sample size.
Simultaneous stenting of multiple SVGs in carefully selected patients has similar in-hospital procedural success and major complications rates, as well as mid-term (18-month) clinical outcomes, as compared with single SVG stenting. Thus, multiple SVG interventions using stents may be a viable revascularization strategy for carefully selected patients and suitable lesions in multiple SVG disease.
Coronary artery bypass graft surgery (CABG) with saphenous vein grafts (SVGs) is limited over the long term by graft failure or a combination of graft failure and progression of coronary atherosclerosis (1–8). Optimal management of these patients remains a subject of debate. Repeat operation may not be an ideal option owing to higher morbidity and mortality as well as poorer outcomes as compared with the first operation (9–11). Percutaneous transluminal coronary angioplasty (PTCA) has been used as an alternative to repeat CABG in selected patients with myocardial ischemia and SVG disease (12). Several variables have been associated with increased risk of complications after angioplasty of SVG lesions (13–19), including old (>3 years), diffusely diseased and totally occluded grafts (13–19)and grafts containing intraluminal thrombus with increased lesion friability and propensity for distal embolization (20,21). There is evidence from the randomized SAphenous VEin De novo (SAVED) trial that stenting may improve the results of catheter-based SVG interventions with a better clinical outcome of six months as compared with PTCA (22). However, in most studies the number of grafts treated has been limited to one procedure at a time, mainly because of the disease being limited to one graft in most patients and concern of increased risk, with simultaneous treatment of several diseased SVGs.
To determine the clinical outcomes in patients with multiple SVG stenting, we evaluated procedural success, major in-hospital complications and mid-term (18-month) clinical events in a consecutive series of patients undergoing a nonstaged multiple SVG intervention with stents as compared with a single SVG stent procedure.
Patients and follow-up
The patient cohort includes a consecutive series of 719 patients (1,147 SVG lesions), found in the Cardiology Research Foundation Angioplasty Database, treated with stents between January 1, 1994 and December 31, 1997. A total of 499 patients underwent “redo” CABG during the same period. Patients were divided into two groups according to the number of treated grafts (1 vs. 2 or 3 SVGs) during a single intervention. Among patients with more than one treated graft, the vast majority (65 [93%] of 70 patients) had a two-graft intervention. All indications for stent use (elective use to improve early procedural safety and to reduce late clinical events, provisional use to treat a suboptimal primary device result or urgent use to treat abrupt or threatened closure) are included in this study. Baseline clinical demographic data and in-hospital complications were confirmed by independent hospital chart review. Angiographic success was defined as <50% residual diameter stenosis with Thrombolysis in Myocardial Infarction (TIMI) flow grade 3. Clinical success was defined as angiographic success without in-hospital complications (death, Q wave myocardial infarction [MI]), emergent CABG). Emergent CABG was defined as CABG performed within 24 h of the index percutaneous procedure.
All patients underwent a pre- and postintervention 12-lead electrocardiogram (ECG) to detect procedure-related ischemic changes or the appearance of a new pathologic Q wave on the surface electrogram, or both. Blood samples were routinely acquired from all patients after the procedure for creatine kinase, MB fraction (CK-MB) enzyme at 8 h and 16 and 24 h (normal values 0 to 4 ng/ml). The diagnosis of non–Q wave MI was based on CK-MB elevation ≥5 times the normal values in the absence of new pathologic Q waves on postintervention ECGs. Clinical outcomes at 18 months were obtained by serial telephone interviews by research nurses, and late clinical events (death, Q wave MI), target lesion revascularization or any cardiac events (death, Q wave MI, coronary angioplasty or CABG) were adjudicated and corroborated by accompanying source documentation. In addition to target lesion revascularization, repeat revascularization is also reported per patient (as any repeat revascularization) and includes all target lesion and target vessel revascularizations for single and multiple SVG disease.
After the initial balloon angioplasty or ablative procedure, coronary stents were implanted over 0.014-in. extrasupport guide wires. All stents used during the study period were included in the current analysis. Adjunct balloon inflation (12 to 16 atm) was operator-dependent after initial stent deployment, with the majority of the operators tending to use lower pressures (12 atm) and with proper apposition of the stent being confirmed by intravascular ultrasound (IVUS). Optimal stent implantation was carefully monitored using an iterative technique with prespecified IVUS end points in the majority of cases. The pre- and post-stent anticoagulation regimens included aspirin (325 mg daily) and ticlopidine (250 mg twice daily) for one month, and additional low molecular weight heparin (for two weeks) in particularly high risk subsets (e.g., thrombus-containing lesions and patients with ≥3 stents). Patients with nonstent SVG procedures, left internal mammary artery interventions and staged stent procedures were excluded from the analysis.
A random sample of 777 of 1,147 lesions was available for complete quantitative and qualitative angiographic analyses. Standard morphologic criteria were used for the identification of lesion location, length, eccentricity, calcification and ulceration. Quantitative angiographic analysis was performed using selected end-diastolic frames demonstrating the stenosis in its most severe projection. Using the contrast-filled guiding catheter as the calibration standard, reference and lesion minimal lumen diameters were determined before and after the intervention.
Continuous variables are presented as the mean value ± SD. Categorical data are presented as percent frequency and compared between the groups using chi-square statistics. Survival curves were calculated and displayed using the SAS LIFETEST procedure. Wilcoxon statistics were used for survival comparison between the two groups (single SVG vs. multiple SVGs). The mean values of nominal data were compared using the unpaired Student ttest. A p value <0.05 was accepted as statistically significant.
Baseline demographic data
Table 1lists the baseline characteristics of all treated patients, distinguished according to the number of SVGs treated (one vs. two or three). Overall, patient demographic data were similar between the two groups. The patient group represents a typical patient cohort undergoing SVG stenting, with a high prevalence of class III or IV unstable angina and relatively old SVGs (age 8.6 ± 4.5 years). Before stent deployment, patients were more often treated with balloons alone. Excimer laser angioplasty was used in 18% and 21% of the patients with a single SVG versus multiple SVGs, respectively (Table 2). Overall, the types of stents used and the average number of stents per lesion were similar between the groups, with the majority of patients in both groups treated with the “biliary” version of the Palmaz-Schatz stent. The number of stents per patient was higher in the multiple SVG group (Table 2). The number of provisional/planned versus urgent stents was similar between the two groups (97% vs. 96% and 3% vs. 4%; p = NS).
Table 3lists the lesion location data for the treated lesions, as well as qualitative and quantitative measurements. By quantitative angiography, the average pre- and post-treatment lesion morphologic and quantitative reference and lesion measurements were similar for both groups, except for angiographic procedural dissections, which were more prevalent in the single SVG group (7.3% vs. 0.8%, p = 0.006). Abrupt closure and “no-reflow” phenomena rates were similar between the two groups (Table 3).
Overall angiographic and procedural success rates were high and similar between the two groups (Table 4). Similarly, major in-hospital complications (death, Q wave MI and emergent CABG) were similar between the groups (2.7% for single SVG and 2.8% for multiple SVG stenting, p = 0.94). Likewise, the prevalence of in-hospital repeat target vessel angioplasty and stent thrombosis was similar between the two groups. However, the periprocedural non Q wave MI rate (defined as CK-MB ≥5 times normal) was nearly doubled in the multiple SVG group (28% vs. 16%, p = 0.009). The use of glycoprotein IIb/IIIa inhibitor (ReoPro) was 4% in the single SVG group versus 6.5% in the multiple SVG group (p = NS). A representative case of multiple SVG stenting is shown in Figure 1.
Clinical follow-up at 18 months was available in 695 (98%) of 712 patients with a single SVG and in 69 (99%) of 70 patients with two or three SVGs (Table 4). There was no difference in late mortality between the groups (5.3% for one SVG vs. 5.6% for two or three SVGs, p = 0.92). The rate of Q wave MI was also similar for multiple SVG versus single SVG stenting at follow-up (4.3% vs. 2.9%, p = 0.55). Overall target lesion revascularization at 18 months was 15% for single SVG stenting versus 11% for multiple SVG stenting (p = 0.19). The two groups were also similar in the requirement for repeat CABG (3.3% vs. 2.2%, p = 0.46) and repeat angioplasty (12% vs. 9%, p = 0.22). The rate of repeat revascularization (calculated per treated patient), was also similar between the two study groups (18% for one SVG vs. 19% for two or three SVGs, p = 0.94). Likewise, actuarial event-free survival curves for any event during 18-month follow-up (death, Q wave MI, angioplasty or CABG) were similar for both groups (62% for one SVG vs. 59% for two or three SVGs, p = 0.75) (Fig. 2).
Logistic regression analysis was used to identify independent predictors of any cardiac event (death, Q wave MI, angioplasty or CABG), target lesion revascularization or any repeat revascularization after SVG stenting (Table 5). Variables expected to predict outcome included in the model were the number of treated grafts (one vs. two or three), the number of stents implanted (one or two vs. three or more), unstable angina, age, gender, history of angioplasty, diabetes mellitus, left ventricular ejection fraction, graft age, reference vessel diameter and final percent diameter stenosis. The presence of diabetes (odds ratio [OR] 1.69) and smaller reference vessel diameter (OR 0.60) were more frequently associated with adverse cardiac events during follow-up. History of angioplasty (OR 1.75), reference vessel diameter (OR 0.71) and final diameter stenosis (OR 0.97) were found to be predictors of target lesion revascularization. The predictors of any repeat revascularization were previous angioplasty (OR 1.52) and reference vessel diameter (OR 0.58) (Table 5). The number of treated vessels or stents implanted did not predict the adverse cardiac events during follow-up.
This study shows that carefully selected patients undergoing a multiple versus single SVG stent intervention have 1) similar in-hospital success and major complications; 2) a nearly doubled prevalence of periprocedural non–Q wave MI (28% vs. 16%, p = 0.009); and 3) similar mid-term (18-month) cardiac events, target lesion revascularization and any repeat revascularization rates, although longer follow-up is required in this patient group. In this large patient cohort we also identified independent predictors of any event or repeat revascularization after stent interventions in SVG disease; previous angioplasty, diabetes mellitus and reference vessel diameter were associated with clinical outcomes in our multivariate model. In none of these analyses did the number of grafts treated or the number of stents used predict adverse cardiac outcomes. Thus, multiple stenting may be a viable therapeutic alternative to repeat CABG in carefully selected patient candidates and suitable lesions in multiple SVG disease.
Previous SVG angioplasty experiences
In a review of 16 contemporary PTCA series comprising 1,571 patients undergoing SVG interventions (without stents), de Feyter et al. (13)reported an overall 88% procedural success rate. In aggregate, ischemic complications were infrequent and included death (1%), MI (4%) and CABG (2%). Distal embolization was reported to occur in 3% of patients. Overall procedural success was slightly lower in lesions involving the proximal versus mid or distal segments. Higher rates of angiographic restenosis were noted in proximal segments (58% vs. 52% and 28% in mid and distal segments, respectively).
Previous SVG stent experiences
Urban et al. (23)summarized their initial SVG Wallstent experiences in 13 patients; the procedure success rate was 100% with 20% restenosis (77% follow-up). Piana et al. (24)and Fenton et al. (25), in two different series, reported restenosis rates of 59% and 34%, respectively, after SVG stenting in single vein grafts. Revascularization rates at 15 months and 1 year were 39% and 23%, respectively. Eeckhout et al. (26)and de Jaegere et al. (27)reported their experiences with the Wallstent in SVGs and found restenosis rates of 18% and 53% and repeat revascularization rates of 32% and 43%, respectively. De Jaegere et al. (27)concluded that stent implantation in SVGs is acceptable, but the long-term clinical outcome may be poor. However, in their study stent implantation was reserved for patients with advanced graft failure and did not include consecutive patients.
Subsequently, Wong et al. (28), in 1995, reported a large series of 589 patients treated for SVG disease and demonstrated a procedural success rate of 97%, with an overall restenosis rate and event-free survival rate (at one year) of 30% and 76%, respectively. More recently, Goy and Eeckhout (29)reported a review of seven SVG stent series in 1,172 patients treated with 1,268 stents (average graft age 8.2 years). They reported an average death rate of 12% and MI rate of 10% at two-year follow-up. Furthermore, the restenosis rate ranged from 18% to 53% (mean 36%). Event-free survival at two years was reported to range from 21% to 81% (mean 50%). The rate of target lesion revascularization was reported to be 21%, with a total revascularization rate of 36%. In most of these studies the Palmaz-Schatz stent was used, although the Wallstent was used in one study and a combination of the two stents was used in an additional study.
Stent implantation versus angioplasty for SVGs
Brener et al. (30)compared the one-year outcome of Palmaz-Schatz stent implantation versus angioplasty for treatment of obstructive lesions in SVGs. In-hospital composite end points (death, MI and emergency CABG) were lower in the stent group (10% vs. 17%, p = 0.059), and adverse cardiac events at one year were lower in the stent group (23% vs. 45%, p < 0.001).
In the recently reported prospective, randomized SAVED trial (22), it was demonstrated that elective stent implantation improves angiographic and clinical outcomes as compared with balloon angioplasty in the treatment of SVG disease. Stenting was associated with superior initial angiographic results, higher rates of procedural success and a trend toward fewer periprocedural non–Q wave MIs. Restenosis occurred in 37% of patients in the stent group and 46% of patients in the PTCA group (p = 0.24). The composite outcome, in terms of freedom from death, MI and CABG, was significantly better in the stent group (73% vs. 58%, p = 0.03). Laham et al. (31)compared multiple native versus multiple SVG stenting in a small group of 33 and 51 patients, respectively. This study showed that death and target site revascularization at one year was similar between the two groups. This study has suggested that multiple SVG stenting may be feasible and safe with acceptable long-term outcomes.
Over the past four study years, we have performed multiple SVG stenting in selected patients, some of whom had multiple previous CABGs (17% vs. 22% in the single SVG group), which made percutaneous revascularization an attractive strategy, when feasible, as compared with “redo” CABG. The 97% procedural success rate and 3% major complication rate underscore the high level of reliability that stenting may offer in the treatment of vein graft disease. The 18-month repeat revascularization rate of 19% and target lesion revascularization rate of 11% are favorable for a subset of patients who characteristically have a high (40% to 60%) restenosis rate and these rates are below those seen in major stent trials.
Our study shows that multiple SVG interventions using stents in carefully selected patients (primarily in patients with two-graft disease) have similar in-hospital procedural success and major complication rates. Angiographic procedural dissections were higher in the single SVG group, emphasizing that multivessel SVG stenting may have been carried out successfully only when the first SVG results are uneventful.
Distal embolization has been noted to be the primary reason for CK-MB elevation in patients undergoing percutaneous interventions for SVG disease. Diffusely diseased vein grafts with thrombus, ulceration and large eccentric plaque volumes have been correlated with distal embolization (32,33). Elevation of CK-MB after successful SVG angioplasty, associated with increased late mortality, has been previously reported by our group (34). That study included patients with SVG disease undergoing all intervention procedures. One-year mortality of 11.7% was demonstrated in the CK-MB–elevated SVG group, which is higher than that in the SVG stent groups reported in the present study (5.3% and 5.6% for single and multiple SVG stenting). However, the higher CK-MB elevations (periprocedural non–Q wave MI rate of 28% vs. 16%) in the multiple SVG group versus single SVG group did not translate into differences in death, Q wave MI and overall cardiac event-free survival at 18 months. This may emphasize the role of stents in SVG disease. One should note, however, that if in-hospital non–Q wave MI events had to be included in the 18-month postintervention analysis, then the overall MI rate would appear to be significantly higher in the multiple SVG stent group during follow-up.
The primary limitation of our study is that despite a large overall interventional volume included in our analysis, the study might have been underpowered to detect differences between the two groups. This is due to the relatively small number of patients (n = 70) included in the multiple SVG group. According to power calculations we find all the powers to be <0.3 (i.e., type II error beta >0.7). On the basis of the rates we found here and assuming a 9:1 ratio between the single versus multiple SVG patient groups, the ability to detect significant differences in overall major in-hospital complications and death would require 2,347,930 (2,113,137:234,793) and 503,660 (453,294:50,366) patients, respectively, at an alpha level of 0.05 with a power of 0.80. Because these numbers are so high, we can say that it may be unrealistic to show a statistically significant difference. This is a retrospective study to assess the efficacy of stents in patients with multiple SVG disease and especially its value as compared with “redo” CABG, as systematic follow-up of these surgical patients is unavailable. It is an observational study emphasizing that multivessel SVG stenting may be performed successfully only when the first SVG results are uneventful, and it does not compare staged, multiple SVG stenting with multiple SVG stenting at the same setting. Second, the vast majority of our patients had the intervention performed in two grafts, and a quarter of the patients had left internal mammary artery grafts as well (25% in the single SVG group vs. 28% in the multiple SVG group). Therefore, the favorable results that we report here are not necessarily applicable to a larger group of patients with disease of three or more grafts. Third, a selected patient group bias may have shown improved results in multiple SVG stenting owing to the fact that the multiple SVG intervention was undertaken only after the primary lesion had been treated successfully. A similar bias may be responsible for the tenfold increase in procedural dissections in the single SVG group; furthermore, the disease in the single SVG group was more severe. An additional limitation may be the relatively infrequent use of adjunctive glycoprotein IIb/IIIa inhibitor therapy during the study period. Although the currently available data to support the systematic use of the glycoprotein IIb/IIIa inhibitor in SVG lesions are limited, it is possible that additional procedural benefit might have been achieved with more frequent use of this potent platelet-blocking drug, as shown in recent angioplasty trials that mainly focused on angioplasty procedures performed in native coronary arteries (35,36). However, a subgroup analysis of 101 SVGs from the Evaluation of IIb/IIIa platelet receptor antagonist 7E3 in Preventing Ischemic Complications (EPIC) trial demonstrated that adjunctive abciximab administration reduced the occurrence of distal embolization and non–Q wave MI (37). This could have had a potential beneficial impact on “major” CK-MB elevations that were frequently observed in our study. The use of low molecular weight heparin during the study period was largely empiric; we used it for complex multiple SVG stenting, and other multiple stenting (38). Finally, the current analysis does not include the use of long Wallstents or newly designed covered stents, which may be more suitable for the treatment of SVG stents. The status of the left internal mammary artery has not been included in the analysis, and its impact on outcome is unknown.
Unlike previous conventional angioplasty experiences, multiple SVG interventions using stents in carefully selected patients (primarily in patients with two-graft disease) have similar in-hospital procedural success and major complication rates, as well as similar mid-term (18-month) clinical outcomes (death, MI and repeat revascularization rates). Thus, multiple SVG interventions using stents may be a viable revascularization strategy for carefully selected patients and suitable lesions in multiple SVG disease.
☆ This study was supported by a grant from the Cardiology Research Foundation, The Washington Cardiology Center, Washington, DC.
- coronary artery bypass graft surgery
- creatine kinase, MB fraction
- intravascular ultrasound
- myocardial infarction
- odds ratio
- percutaneous transluminal coronary angioplasty
- SAphenous VEin De novo trial
- saphenous vein graft
- Thrombolysis in Myocardial Infarction trial
- Received February 1, 1999.
- Revision received August 24, 1999.
- Accepted October 25, 1999.
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