Study Question: The investigators sought to examine theeffects of local VEGF gene delivery during angioplasty(PTCA) and stenting.Methods: The study design was a randomized, placebo-controlled double-blind phase II trial. Patients with coro-nary disease (n103; Canadian Cardiovascular Society an-gina class II to III; mean age, 586 years) were recruitedand PTCA performed with standard methods followed bygene transfer with a perfusion-infusion catheter. Ninetypercent of the patients received stents; 37 patients receivedVEGF adenovirus (VEGF-Adv), 28 patients received VEGFplasmid liposome (VEGF-P/L) and 38 control patients re-ceived Ringers lactate. The primary end points were theminimal lumen diameter and diameter stenosis measuredby quantitative coronary angiography (QCA) at 6-monthfollow-up.Results: Gene transfer to coronary arteries was feasible andwell tolerated. The overall restenosis rate was 6%. In quan-titative coronary angiography analysis, the minimal lumendiameter and percent of diameter stenosis did not signifi-cantly differ between the study groups. However, myocar-dial perfusion showed a significant improvement in theVEGF-Advtreated patients at 6-month follow-up. Someinflammatory responses were transiently present in theVEGF-Adv group, but no increases were detected in theincidences of serious adverse events in any of the studygroups.Conclusions: The authors concluded that gene transfer withVEGF-Adv or VEGF-P/L during PTCA and stenting can beperformed safely. There was a significant increase in myo-cardial perfusion in the VEGF-Advtreated patients; how-ever, there were no significant differences in clinical reste-nosis rate or minimal lumen diameter at the 6-monthfollow-up.Perspective: This randomized, double-blind placebo-con-trolled trial evaluating local intracoronary VEGF gene trans-fer for prevention of restenosis after coronary angioplastydemonstrated that catheter-mediated gene transfer is safeand well tolerated. The treatment did not affect the inci-dence of postangioplasty restenosis but was associated witha significant improvement in myocardial perfusion in theVEGF-Advtreated patients. Longer term follow-up will berequired to test whether the improvement in perfusiontranslates into better clinical outcomes. DM
Intracoronary -Irradiation With a Rhenium-188 Filled Balloon Catheter: A Randomized Trial inPatients With De Novo and Restenotic Lesions
Hoher M, Wohrle J, Wohlfrom M, et al. Circulation 2003;107:30227.
Study Question: The investigators studied the efficacy of aself-centering liquid rhenium-188filled balloon catheterfor coronary -brachytherapy.
Methods: The study design was a randomized placebo-controlled trial. After successful coronary angioplasty withor without stenting, 225 patients (71% de novo lesions)were randomly assigned to receive 22.5 Gy intravascular-irradiation in 0.5-mm tissue depth (n113) or to receiveno additional intervention (n112). The primary end pointwas the restenosis rate at the target lesion at 6 months.Secondary end points were the restenosis rate of the totalsegment including edge stenoses and the incidence of majoradverse cardiac events (MACE) defined as cardiac death,myocardial infarction, and repeat revascularization of thetarget vessel.Results: After 6 months of follow-up, late loss was signifi-cantly lower in the irradiated group compared with thecontrol group, both of the target lesion (0.110.54 vs.0.690.81 mm, p0.0001) and of the total segment(0.220.67 vs. 0.700.82 mm, p0.0001). This was alsoevident in the subgroup of patients with de novo lesionsand independent from stenting. Binary restenosis rates weresignificantly lower at the target lesion (6.3% vs. 27.5%,p0.0001) and of the total segment (12.6% vs. 28.6%,p0.007) after rhenium-188 brachytherapy comparedwith the control group. Target vessel revascularization ratewas significantly lower in the rhenium-188 (6.3%) com-pared with the control group (19.8%, p0.006).Conclusions: The authors conclude that intracoronary-brachytherapy with a rhenium-188 liquid-filled balloonis safe and efficiently reduces restenosis and revasculariza-tion rates after coronary angioplasty.Perspective: This randomized trial of a self-centering liquidrhenium-188filled balloon catheter for coronary -irradi-ation showed a significantly reduced restenosis rate at 6months. The efficacy of rhenium-188 brachytherapy wasalso evident in de novo lesions and independent fromadditional stenting. Gamma- and -irradiation has beenshown to be effective for the treatment of in-stent restenosisin prior studies and -irradiation using a strontium-90/yttrium-90 coil source has been shown to decrease resteno-sis rates in de novo lesions. An effective liquid-filled balloonmay provide significant advantages as the diameter andlength of the irradiation balloon can be easily adapted to theindividual vessel segment. DM
Relation of Mortality of Primary Angioplasty DuringAcute Myocardial Infarction to Door toThrombolysis in Myocardial Infarction (TIMI) Time
Juliard JM, Feldman LJ, Golmard JL, et al. Am J Cardiol 2003;91:14015.
Study Question: To evaluate in a cohort of patients withST-segment elevation acute myocardial infarction [AMI],relations among ischemic time (chest painTIMI 3 time),in-hospital delays (door to TIMI 3 time) and in-hospitalsurvival.
ACC CURRENT JOURNAL REVIEW Sep/Oct 2003
Methods: This single-center cohort study included 499 pa-tients (mean age 59 years; 80% men) who underwentsuccessful primary percutaneous transluminal coronary an-gioplasty (PTCA) for AMI admitted 6 hours after symp-tom onset. The population was divided into tertiles withrespect to time between onset of symptoms and admission,onset of symptoms to Thrombolysis In Myocardial Infarc-tion (TIMI) grade 3 flow and time from admission to TIMIgrade 3 flow. Univariate analysis and multiple logistic re-gression was performed to assess the relation between pre-dictor variables and in-hospital mortality.Results: The overall in-hospital mortality rate was 3.2%.There was no significant relation between the various ter-tiles of time intervals and in-hospital mortality. After linearlogistic regression, only age (odds ratio [OR] 1.79 per 10years), female gender (OR 3.56) and door-to-TIMI 3 time(OR 1.27 per 15 minutes) were independently correlatedwith in-hospital mortality.Conclusions: The authors observed a continuous but non-significant trend of higher mortality when chest pain-to-TIMI 3 time increased. The study demonstrates a significantrelation between door-to-TIMI 3 time and mortality.Perspective: There is unequivocal evidence that in patientswith ST-segment elevation AMI treated with fibrinolytictherapy, the benefit of treatment decreases with the delaybetween the onset of symptoms and the administration oftherapy. However, there is controversy as to whether thistime dependency of treatment benefit holds true for me-chanical revascularization, i.e., primary angioplasty. Oneexplanation may be that efficacy of primary angioplasty torecanalize the infarct-related artery (IRA) may be time in-dependent, whereas this is not the case with fibrinolytictherapy. The present study seems to suggest that there is norelation between chest pain to TIMI 3 time. Although themortality rates are not statistically different, they could beclinically important (1.8% mortality for reperfusion at0180 minutes and 4.8% for reperfusion at 255540 min-utes, a 3% absolute difference). The statistical non-signifi-cance is likely related to small sample size and inadequatepower. The current goal of management of STEMI shouldbe early and complete revascularization of the IRA withprotocols in place to minimize delays wherever possi-ble. DM
Clinical Outcome of Patients Undergoing Non-Cardiac Surgery in the 2 Months FollowingCoronary StentingWilson SH, Fasseas P, Orford JL, et al. J Am Coll Cardiol 2003;42:234 40.
Study Question: The investigators sought to determine thefrequency and timing of complications when surgery wasperformed within 2 months of coronary stent placement.Methods: The study was a retrospective cohort analysis. Theinvestigators analyzed the Mayo Clinic Percutaneous Coro-
nary Intervention and Surgical databases between 1990 and2000 and identified 207 patients who underwent surgery inthe 2 months following successful coronary stent place-ment.Results: Eight patients (4.0%) died or suffered a myocardialinfarction or stent thrombosis. All 8 patients were amongthe 168 patients (4.8%, 95% confidence interval [CI] 2.19.2) undergoing surgery 6 weeks after stent placement; thefrequency of these events ranged from 3.87.1% per weekduring each of the 6 weeks. No events occurred in the 39patients undergoing surgery 79 weeks after stent place-ment (0%, 95% CI 0.09.0).Conclusions: The authors conclude that whenever possible,non-cardiac surgery should be delayed 6 weeks after stentplacement, by which time stents are generally endothelial-ized, and a course of antiplatelet therapy to prevent stentthrombosis has been completed.Perspective: The primary finding of this study is that the riskof stent thrombosis and other major complications afternon-cardiac surgery is greatest in the first 6 weeks after stentplacement and less thereafter. Delaying elective surgery forup to 6 weeks after stenting and at least a 46 week courseof therapy with aspirin and a thienopyridine seems opti-mal. DM
Long-Term Outcome of Patients with Silent VersusSymptomatic Ischemia Six Months afterPercutaneous Coronary Intervention and StentingZellweger MJ, Weinbacher M, Zutteret AW, et al. J Am CollCardiol 2003;42:33 40.
Study Question: The investigators sought to evaluate theincidence of silent ischemia vs. symptomatic ischemia 6months after percutaneous coronary intervention (PCI) andits impact on prognosis. They also tested the utility ofmyocardial perfusion single-photon emission computedtomography (SPECT), or MPS, for ri