Two-year follow-up after catheter-based radiotherapy to inhibit coronary restenosis.

BACKGROUND: Although early trials indicate the treatment of restenosis with radiation therapy is safe and effective, the long-term impact of this new technology has been questioned. The possibility of late untoward consequences, such as aneurysm formation, perforation, and accelerated vascular disease, is of significant concern. Furthermore, it is not known whether the beneficial effects of radiation therapy will be durable or whether radiation will only delay restenosis. METHODS AND RESULTS: A double-blind, randomized trial was undertaken to compare 192Ir with placebo sources in patients with previous restenosis after coronary angioplasty. Patients were randomly assigned to receive a 0.76-mm (0. 03-in) ribbon containing sealed sources of either 192Ir or placebo. All patients underwent repeat coronary angiography at 6 months. All living patients were contacted 24 months after their index study procedure. Patients were assessed with respect to the need for target-lesion revascularization or nontarget-lesion revascularization, occurrence of myocardial infarction, or death. Over a 9-month period, 55 patients were enrolled; 26 were randomized to 192Ir and 29 to placebo. Follow-up was obtained in 100% of living patients at a minimum of 24 months. Target-lesion revascularization was significantly lower in the 192Ir group (15.4% versus 44.8%; P<0. 01). Nontarget-lesion revascularization was similar in 192Ir and placebo patients (19.2% versus 20.7%; P=NS). There were 2 deaths in each group. The composite end point of death, myocardial infarction, or target-lesion revascularization was significantly lower in 192Ir-treated versus placebo-treated patients (23.1% versus 51.7%; P=0.03). No patient in the 192Ir group sustained a target-lesion revascularization later than 10 months. CONCLUSIONS: At 2-year clinical follow-up, treatment with 192Ir demonstrates significant clinical benefit. Although further follow-up (including late angiography) will be necessary, no clinical events have occurred to date in the 192Ir group to suggest major untoward effects of vascular radiotherapy. At the intermediate follow-up time point, vascular radiotherapy continues to be a promising new treatment for restenosis.

Three-year clinical and angiographic follow-up after intracoronary radiation : results of a randomized clinical trial.

BACKGROUND: Although several early trials indicate treatment of restenosis with radiation therapy is safe and effective, the long-term impact of this new technology has been questioned. The objective of this report is to document angiographic and clinical outcome 3 years after treatment of restenotic stented coronary arteries with catheter-based (192)Ir. METHODS AND RESULTS: A double-blind, randomized trial compared (192)Ir with placebo sources in patients with previous restenosis after coronary angioplasty. Over a 9-month period, 55 patients were enrolled; 26 were randomized to (192)Ir and 29 to placebo. At 3-year follow-up, target-lesion revascularization was significantly lower in the (192)Ir group (15. 4% versus 48.3%; P<0.01). The dichotomous restenosis rate at 3-year follow-up was also significantly lower in (192)Ir patients (33% versus 64%; P<0.05). In a subgroup of patients with 3-year angiographic follow-up not subjected to target-lesion revascularization by the 6-month angiogram, the mean minimal luminal diameter between 6 months and 3 years decreased from 2.49+/-0.81 to 2.12+/-0.73 mm in (192)Ir patients but was unchanged in placebo patients. CONCLUSIONS: The early clinical benefits observed after treatment of coronary restenosis with (192)Ir appear durable at late follow-up. Angiographic restenosis continues to be significantly reduced in (192)Ir-treated patients, but a small amount of late loss was observed between the 6-month and 3-year follow-up time points. No events occurred in the (192)Ir group to suggest major untoward effects of vascular radiotherapy. At 3-year follow-up, vascular radiotherapy continues to be a promising new treatment for restenosis.

Effect of intracoronary gamma-radiation therapy on in-stent restenosis: An intravascular ultrasound analysis from the gamma-1 study.

BACKGROUND: The aim of this study was to use serial volumetric intravascular ultrasound to evaluate the effect of gamma-radiation on recurrent in-stent restenosis. METHODS AND RESULTS: After successful reintervention, patients were randomized to receive either (192)Ir or placebo. Intravascular ultrasound studies with motorized pullback (0.5 mm/s) were performed immediately after irradiation and at 8-month follow-up in 70 patients. Paired volumetric analysis of the stented segment and of 5-mm proximal and distal reference segments was performed; this included measurements of the external elastic membrane, lumen, plaque and media (external elastic membrane minus lumen), stent, and intimal hyperplasia (stent minus lumen). Baseline proximal reference, stent, and distal reference measurements were similar in both groups. The changes in proximal and distal reference measurements of the external elastic membrane, plaque and media, and lumen areas were similar in both groups. However, the decrease in stented segment lumen volume was less in the (192)Ir patients than the placebo patients (-25+/-34 mm(3) versus -48+/-42 mm(3); P:=0.0225), and the increase in the volume of intimal hyperplasia in the stented segment was less in the (192)Ir patients than in the placebo patients (28+/-37 mm(3) versus 50+/-40 mm(3); P:=0.0352). When averaged over the length of the stented segment (32+/-13 mm versus 33+/-14 mm; P:=0.9), the increase in mean area of intimal hyperplasia was 0.8+/-1.0 mm(2) in the (192)Ir group and 1.6+/-1.2 mm(2) in the control group (P:=0.0065). Late stent-vessel wall malapposition was noted in one placebo patient and no (192)Ir patients. CONCLUSIONS: gamma-Radiation therapy can effectively prevent recurrent in-stent restenosis by inhibiting neointimal formation within the stent. At the stent edge, there were no significant differences between (192)Ir and placebo patients.

Final results of the Can Routine Ultrasound Influence Stent Expansion (CRUISE) study.

BACKGROUND: Intravascular ultrasound (IVUS) can assess stent geometry more accurately than angiography. Several studies have demonstrated that the degree of stent expansion as measured by IVUS directly correlated to clinical outcome. However, it is unclear if routine ultrasound guidance of stent implantation improves clinical outcome as compared with angiographic guidance alone. METHODS AND RESULTS: The CRUISE (Can Routine Ultrasound Influence Stent Expansion) study, a multicenter study IVUS substudy of the Stent Anti-thrombotic Regimen Study, was designed to assess the impact of IVUS on stent deployment in the high-pressure era. Nine centers were prospectively assigned to stent deployment with the use of ultrasound guidance and 7 centers to angiographic guidance alone with documentary (blinded) IVUS at the conclusion of the procedure. A total of 525 patients were enrolled with completed quantitative coronary angiography, quantitative coronary ultrasound, and clinical events adjudicated at 9 months for 499 patients. The IVUS-guided group had a larger minimal lumen diameter (2.9+/-0.4 versus 2.7+/-0. 5 mm, P<0.001) by quantitative coronary angiography and a larger minimal stent area (7.78+/-1.72 versus 7.06+/-2.13 mm(2), P<0.001) by quantitative coronary ultrasound. Target vessel revascularization, defined as clinically driven repeat interventional or surgical therapy of the index vessel at 9 month-follow-up, occurred significantly less frequently in the IVUS-guided group (8.5% versus 15.3%, P<0.05; relative reduction of 44%). CONCLUSIONS: These data suggest that ultrasound guidance of stent implantation may result in more effective stent expansion compared with angiographic guidance alone.

Point-of-care measured platelet inhibition correlates with a reduced risk of an adverse cardiac event after percutaneous coronary intervention: results of the GOLD (AU-Assessing Ultegra) multicenter study.

BACKGROUND: The optimal level of platelet inhibition with a glycoprotein (GP) IIb/IIIa antagonist necessary to minimize thrombotic complications in patients undergoing a percutaneous coronary intervention (PCI) is currently unknown. METHODS AND RESULTS: Five hundred patients undergoing a PCI with the planned use of a GP IIb/IIIa inhibitor had platelet inhibition measured at 10 minutes, 1 hour, 8 hours, and 24 hours after the initiation of therapy with the Ultegra Rapid Platelet Function Assay (Accumetrics). Major adverse cardiac events (MACES: composite of death, myocardial infarction, and urgent target vessel revascularization) were prospectively monitored, and the incidence correlated with the measured level of platelet function inhibition at all time points. One quarter of all patients did not achieve >/=95% inhibition 10 minutes after the bolus and experienced a significantly higher incidence of MACEs (14.4% versus 6.4%, P=0.006). Patients whose platelet function was <70% inhibited at 8 hours after the start of therapy had a MACE rate of 25% versus 8.1% for those >/=70% inhibited (P=0.009). By multivariate analysis, platelet function inhibition >/=95% at 10 minutes after the start of therapy was associated with a significant decrease in the incidence of a MACE (odds ratio 0.46, 95% CI 0.22 to 0.96, P=0.04). CONCLUSIONS: Substantial variability in the level of platelet function inhibition is achieved with GP IIb/IIIa antagonist therapy among patients undergoing PCI. The level of platelet function inhibition as measured by a point-of-care assay is an independent predictor for the risk of MACEs after PCI.

Repeat coronary angioplasty: efficacy of a third angioplasty for a second restenosis.

To determine the efficacy of repeat percutaneous transluminal coronary angioplasty, 74 patients were studied who underwent a third angioplasty for a second restenosis of one coronary artery segment. The procedure was successful in 93% of patients. Procedural complications included emergency bypass surgery (three patients) and in-hospital death (two patients). At late follow-up (mean 18 months, range 7 to 49), 30 patients (43%) had a third restenosis treated with either a fourth angioplasty (16 patients), coronary bypass surgery (11 patients) or medical management (1 patient). Thirty-nine patients (57%) had no restenosis on the basis of follow-up angiography or absence of symptoms previously attributed to restenosis. Factors associated with a third restenosis included a shorter time interval (less than 3 months) between previous angioplasty procedures and dilation of the left anterior descending coronary artery. Among the 16 patients undergoing a fourth angioplasty for a third restenosis, the procedural success rate was 94%. One patient required emergency bypass surgery. At late follow-up (mean 16 months, range 7 to 38), eight patients (53%) had a fourth restenosis treated with either a fifth angioplasty (one patient), bypass surgery (five patients) or medical management (two patients). Considering all 74 patients undergoing a third angioplasty for a second restenosis, 27% had bypass surgery, 5% died, 4% were managed medically and 64% were free of angina at late follow-up after either a third, fourth or fifth angioplasty. Restenosis rates after a third or fourth angioplasty procedure for recurrent restenosis are higher than those for the initial procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

High speed rotational coronary atherectomy for patients with diffuse coronary artery disease.

High speed rotational coronary atherectomy was undertaken using the Rotablator in 42 patients who were suboptimal candidates for balloon angioplasty. Most patients (71%) had diffuse coronary artery disease, defined as a stenosis greater than 1 cm in length. Previous restenosis after balloon angioplasty was present in 21% and 10% had an ostial lesion. Adjunctive balloon angioplasty was not used to reduce residual stenosis after atherectomy. The procedure was successful in 76% of patients. Procedural success was achieved in 92% of patients with a lesion less than or equal to 1 cm in length, but in only 70% of patients with a lesion greater than 1 cm in length (p less than 0.01). One patient sustained abrupt closure of the target vessel, resulting in emergency bypass surgery and death. Small non-Q wave myocardial infarction occurred in eight patients (19%) and was associated with a longer lesion. The mean peak creatine kinase value in patients with non-Q wave myocardial infarction was 683 U/liter. Transient regional wall motion abnormalities were noted on the postatherectomy left ventricular angiogram in four of the eight patients with non-Q wave myocardial infarction. Follow-up angiography (at a mean interval of 6.2 +/- 2.6 months) was performed in 91% of patients and revealed restenosis (greater than 50% narrowing) in 59% The resistance rate was 22% for short lesions (less than or equal to 1 cm) and 75% for long lesions (greater than 1 cm) (p less than 0.05). In this study, the results of high speed rotational coronary atherectomy were strongly influenced by lesion length.(ABSTRACT TRUNCATED AT 250 WORDS)

Prophylactic versus standby cardiopulmonary support for high risk percutaneous transluminal coronary angioplasty.

OBJECTIVES: Data from a national registry of 23 centers using cardiopulmonary support (CPS) were analyzed to compare the risks and benefits of prophylactic CPS versus standby CPS for patients undergoing high risk coronary angioplasty. BACKGROUND: Early data from the CPS registry documented a high angioplasty success rate as well as a high procedural morbidity rate. Because of this increased morbidity some high risk patients were placed on standby CPS instead of prophylactic CPS. METHODS: Patients in the prophylactic CPS group had 18F or 20F venous and arterial cannulas inserted and cardiopulmonary bypass initiated. Patients in the standby CPS group were prepared for institution of cardiopulmonary bypass, but bypass was not actually initiated unless the patient sustained irreversible hemodynamic compromise. RESULTS: There were 389 patients in the prophylactic CPS group and 180 in the standby CPS group. The groups were comparable with respect to most baseline characteristics, except that left ventricular ejection fraction was lower in the prophylactic CPS group. Thirteen of the 180 patients in the standby CPS group sustained irreversible hemodynamic compromise during the angioplasty procedure. Emergency institution of CPS was successfully initiated in 12 of these 13 patients in < 5 min. Procedural success was 88.7% for the prophylactic and 84.4% for the standby CPS group (p = NS). Major complications did not differ between groups. However, 42% of patients in the prophylactic CPS group sustained femoral access site complications or required blood transfusions, compared with only 11.7% of patients in the standby CPS group (p < 0.01). Among patients with an ejection fraction < or = 20%, procedural morbidity remained significantly higher in the prophylactic CPS group (41% vs. 9.4%, p < 0.01), but procedural mortality was higher in the standby group (4.8% vs. 18.8%, p < 0.05). CONCLUSIONS: Patients in the standby and prophylactic CPS groups had comparable success and major complication rates, but procedural morbidity was higher in the prophylactic group. When required, standby CPS established immediate hemodynamic support during most angioplasty complications. For most patients, standby CPS was preferable to prophylactic CPS during high risk coronary angioplasty. However, patients with extremely depressed left ventricular function (ejection fraction < 20%) may benefit from institution of prophylactic CPS.

Long-term angiographic and clinical outcome after implantation of a balloon-expandable stent in the native coronary circulation. Palmaz-Schatz Stent Study Group.

OBJECTIVES: The purpose of this study was to examine the long-term clinical and angiographic outcome after coronary stent implantation. BACKGROUND: Previous reports have shown a discordance between the excellent initial angiographic results and subsequent adverse clinical events after coronary artery stenting. METHODS: Single Palmaz-Schatz stents were electively implanted in the native coronary arteries of 300 consecutive patients. Angiograms were obtained at baseline, after balloon angioplasty, after stent implantation and at 6 months after implantation. Films were analyzed by a panel of angiographers utilizing an automated edge detection program. Clinical events, including death, myocardial infarction, coronary bypass surgery and repeat angioplasty, were recorded for 1 year. RESULTS: Although there were no acute in laboratory vessel closures, stent thrombosis occurred in 14 patients (4.7%) at a mean +/- SD of 5 +/- 3 days after implantation. Two hundred fifty-eight (90%) of 286 eligible patients had follow-up angiography at 6.1 +/- 2.2 months after stent implantation. Minimal lumen diameter increased from 0.80 +/- 0.39 mm at baseline to 1.65 +/- 0.51 mm after angioplasty and further increased to 2.55 +/- 0.49 mm after stent placement (p = 0.0001). At follow-up there was a 0.85-mm late loss in lumen diameter, with a final minimal lumen diameter at 6 months of 1.70 +/- 0.71 mm. Restenosis, defined as > or = 50% diameter stenosis at follow-up, occurred in 14% of patients with previously untreated lesions and in 39% of patients with previous angioplasty (p < 0.001). Clinical events after 1 year for the entire group of 300 patients included death in 0.7%, myocardial infarction in 3.7%, bypass grafting in 8% and repeat angioplasty in 13%. Freedom from any adverse clinical event was 80% for all treated patients and 87% for those with previously untreated lesions. CONCLUSIONS: Elective use of this balloon-expandable stent in the native coronary circulation is associated with a low restenosis rate by quantitative angiography in previously untreated lesions and a favorable clinical outcome with an excellent event-free survival rate at 1 year.

A randomized, placebo-controlled trial of enoxaparin after high-risk coronary stenting: the ATLAST trial.

OBJECTIVES: We performed a multicenter, double-blind placebo-controlled trial to examine the efficacy and safety of enoxaparin in patients at high risk for stent thrombosis (ST). BACKGROUND: The optimal antithrombotic regimen for such patients is unknown. METHODS: We randomized 1,102 patients with clinical, angiographic or ultrasonographic features associated with an increased risk of ST to receive either twice-daily injections of weight-adjusted enoxaparin or placebo for 14 days after stenting. All patients received aspirin and ticlopidine. The primary end point was a 30-day composite end point of death, myocardial infarction (MI) or urgent revascularization. RESULTS: The target enrollment for the study was 2,000 patients. However, the trial was terminated prematurely at 1,102 patients after interim analysis revealed an unexpectedly low event rate. The primary outcome occurred in 1.8% enoxaparin-treated patients versus 2.7% treated with placebo (odds ratio [OR] 0.66; 95% confidence interval [CI] 0.29 to 1.5, p = 0.30); for death or MI the rates were 0.9% vs. 2.2%, respectively (OR 0.41, 95% CI 0.14 to 1.2, p =0.13); and for MI, 0.4% vs. 1.6%, respectively (OR 0.22, 95% CI 0.05 to 0.99, p = 0.04). The groups had comparable rates of major bleeding (3.3% for enoxaparin, 1.6% for placebo, p =0.08), but minor nuisance bleeding was increased with enoxaparin (25% vs. 5.1%, p < 0.001). CONCLUSIONS: The clinical outcomes of patients at increased risk of ST are more favorable than previously reported, rendering routine oral antiplatelet therapy adequate for most. However, given its relative safety and potential to reduce the risk of subsequent infarction, a 14-day course of enoxaparin may be considered for carefully selected patients.

Immediate results and late outcomes after stent implantation in saphenous vein graft lesions: the multicenter U.S. Palmaz-Schatz stent experience. The Palmaz-Schatz Stent Study Group.

OBJECTIVES: This study reports the multicenter registry experience evaluating the safety and efficacy of the Palmaz-Schatz stent in the treatment of saphenous vein graft disease. BACKGROUND: Saphenous vein graft angioplasty is associated with frequent periprocedural complications and a high frequency of restenosis. Stent implantation has been shown to reduce restenosis, with improved long-term outcomes in the treatment of native coronary artery disease. Preliminary experience with stent placement in the treatment of saphenous vein graft lesions has been favorable. METHODS: Twenty U.S. investigator sites enrolled a total of 589 symptomatic patients (624 lesions) for treatment of focal vein graft stenoses between January 1990 and April 1992. Follow-up angiography was performed at 6 months, and the clinical course of all study patients was prospectively collected at regular intervals for up to 12 months. RESULTS: Stent delivery was successful in 98.8% of cases, and the procedural success rate was 97.1%. The lesion diameter stenosis decreased from 82 +/- 12% (mean +/- SD) before to 6.6 +/- 10.2% after treatment. Major in-hospital complications occurred in 17 patients (2.9%); stent thrombosis was found in 8 (1.4%); and major vascular or bleeding complications were noted in 83 (14.3%). Six-month angiographic follow-up revealed an overall restenosis rate (> or = 50% diameter stenosis) of 29.7%. Multivariate logistic regression analysis indicated that 1) restenotic lesions, 2) smaller reference vessel size, 3) history of diabetes mellitus, and 4) higher percent poststent diameter stenosis were independent predictors of restenosis. The 12-month actuarial event-free survival was 76.3%. CONCLUSIONS: Stent implantation in patients with focal saphenous vein graft lesions can be achieved with a high rate of procedural success, acceptable major complications, reduced angiographic restenosis and favorable late clinical outcome compared with historical balloon angioplasty control series. The rigorous anticoagulation regimen after stent placement results in more frequent vascular and other bleeding complications. Future randomized studies comparing standard balloon angioplasty with stent implantation are warranted to properly assess the full impact of stent placement in the treatment of saphenous vein graft lesions.

Retrieval and analysis of particulate debris after saphenous vein graft intervention.

OBJECTIVES: This study was designed to evaluate the composition and quantity of particulate debris resulting from vein graft intervention. BACKGROUND: Distal embolization and "no reflow" are frequent and important complications resulting from angioplasty of diseased saphenous vein grafts. Little is known about the composition and quantity of embolic particulate debris associated with vein graft intervention, and no intervention has been shown to protect against its clinical consequences. METHODS: A catheter system, designed to contain, retrieve and protect against distal embolization of this material, was evaluated during 27 percutaneous interventional saphenous vein graft procedures. Clinical, angiographic and pathologic analyses were performed. RESULTS: The duration of distal graft occlusion required to allow intervention and subsequent debris removal was 150 +/- 54 s, decreasing as experience was gained. Thrombolysis in Myocardial Infarction trial (TIMI) flow grade increased from 2.6 +/- 0.8 to 3.0 +/- 0.0. Creatine kinase (CK) rose above normal in three patients (11.1%) exceeding 3x normal in one (3.7%) resulting in the diagnosis of non-Q-myocardial infarction. Particulate material was identified following 21 of 23 procedures suitable for analysis. Particle size was 204 +/- 57 microm in the major axis and 83 +/- 22 microm in the minor axis. Particles consisted predominantly of soft acellular atheromatous material, such as that typically found under a fibrous cap. Semiquantitative analysis suggested that the quantity of particulate material was less following stenting than following balloon dilation. CONCLUSIONS: Particulate matter is commonly present following routine angioplasty and stenting of saphenous vein grafts. Containment, retrieval and analysis of this particulate debris are all feasible. Comparison to prior clinical experience is limited by small sample size. However, to the extent that these particles may contribute to distal embolization, no-reflow and infarction, such a system may contribute to the reduction of complications following vein graft intervention.

Long-term vessel response to a self-expanding coronary stent: a serial volumetric intravascular ultrasound analysis from the ASSURE Trial.A Stent vs. Stent Ultrasound Remodeling Evaluation.

OBJECTIVES: We sought to investigate the in vivo mechanical properties of a new self-expanding coronary stent (RADIUS) and, particularly, the subsequent vessel response over time. BACKGROUND: Preclinical studies have suggested that self-expanding stents may produce less vessel wall injury at initial deployment, leading to larger follow-up lumens than with balloon-expandable stents. However, the influence of the chronic stimulus from self-expanding stents on the vessel wall remains unknown. METHODS: Sixty-two patients were randomly assigned to either the RADIUS self-expanding stent group (n = 32) or the Palmaz-Schatz balloon-expandable stent group (n = 30). Intravascular ultrasound was performed after stent deployment and at six-month follow-up. RESULTS: At follow-up, the RADIUS stents had increased 23.6% in overall volume, while the Palmaz-Schatz stents had remained unchanged. Due to the greater mean neointimal area (3.0 +/- 1.7 mm2 vs. 1.9 +/- 1.2 mm2, p = 0.02) in the RADIUS group, no significant difference in net late lumen loss was observed between the two groups. On the other hand, analysis at the peristent margins demonstrated that mean late loss was significantly smaller in the RADIUS group than it was in the Palmaz-Schatz group (0.1 +/- 2.1 mm2 vs. 1.9 +/- 2.4 mm2, p = 0.02). CONCLUSIONS: Serial volumetric IVUS revealed that the RADIUS stents continued to enlarge during the follow-up period. In this stent implantation protocol, this expansion was accompanied by a greater amount of neointima than the Palmaz-Schatz stents, resulting in similar late lumen loss in both configurations. In the peristent margins, however, late lumen loss was minimized with the RADIUS stents.

Clinical outcomes after detection of elevated cardiac enzymes in patients undergoing percutaneous intervention. IMPACT-II Investigators. Integrilin (eptifibatide) to Minimize Platelet Aggregation and Coronary Thrombosis-II.

OBJECTIVES: We examined the relations of elevated creatine kinase (CK) and its myocardial band isoenzyme (CK-MB) to clinical outcomes after percutaneous coronary intervention (PCI) in patients enrolled in Integrilin (eptifibatide) to Minimize Platelet Aggregation and Coronary Thrombosis-II (trial) (IMPACT-II), a trial of the platelet glycoprotein IIb/IIIa inhibitor eptifibatide. BACKGROUND: Elevation of cardiac enzymes often occurs after PCI, but its clinical implications are uncertain. METHODS: Patients undergoing elective, scheduled PCI for any indication were analyzed. Parallel analyses investigated CK (n=3,535) and CK-MB (n=2,341) levels after PCI (within 4 to 20 h). Clinical outcomes at 30 days and 6 months were stratified by postprocedure CK and CK-MB (multiple of the site's upper normal limit). RESULTS: Overall, 1,779 patients (76%) had no CK-MB elevation; CK-MB levels were elevated to 1 to 3 times the upper normal limit in 323 patients (13.8%), to 3 to 5 times normal in 84 (3.6%), to 5 to 10 times normal in 86 (3.7%), and to >10 times normal in 69 patients (2.9%). Elevated CK-MB was associated with an increased risk of death, reinfarction, or emergency revascularization at 30 days, and of death, reinfarction, or surgical revascularization at 6 months. Elevated total CK to above three times normal was less frequent, but its prognostic significance paralleled that seen for CK-MB. The degree of risk correlated with the rise in CK or CK-MB, even for patients with successful procedures not complicated by abrupt closure. CONCLUSIONS: Elevations in cardiac enzymes, including small increases (between one and three times normal) often not considered an infarction, are associated with an increased risk for short-term adverse clinical outcomes after successful or unsuccessful PCI.

Source displacement during the cardiac cycle in coronary endovascular brachytherapy.

PURPOSE: Preliminary clinical trials employing catheter-based endovascular brachytherapy show promising results in reducing restenosis after coronary intervention. Failure analysis of these studies showed a significant number of failures at the treatment margin. It is hypothesized that one of the possible causes for marginal failure is the longitudinal seed movement during the brachytherapy procedure. In this study a quantitative analysis was performed to determine the magnitude of the source displacement during the cardiac cycle. METHODS AND MATERIALS: Cine-angiograms of the Iridium-192 (Ir-192) active source seeds or dummy source seeds in place were reviewed frame by frame for 30 patients enrolled from various clinical trials using the Cordis catheter delivery system with a Ir-192 seed ribbon. The proximal and distal source points were measured in reference to branching vessels closest to the respective seed during the contrast phase of the cine-angiogram. The two frames showing the maximum source displacement were captured. After appropriate demagnification, longitudinal source displacement was measured. The data were tabulated for proximal vs. distal ends and for different coronary vessels. RESULTS: The longitudinal source displacement is significant with overall mean and standard deviation of 1.1 and 0.8 mm, respectively. The range is from 0.0 to 5.4 mm. CONCLUSION: The contribution of source movement should be included into the treatment length to avoid "geographic miss" and the subsequent marginal failure.

A subgroup analysis of the Scripps Coronary Radiation to Inhibit Proliferation Poststenting Trial.

INTRODUCTION: In the Scripps Coronary Radiation to Inhibit Proliferation Poststenting (SCRIPPS) Trial, 192Ir significantly reduced angiographic, ultrasonographic, and clinical endpoints of restenosis. The objective of this analysis was to quantitate the impact of patient, lesion and technical characteristics on late angiographic outcome. METHODS: Patients with restenotic, stented coronary lesions were randomized to receive either 192Ir or placebo sources. Late luminal loss and loss index were calculated for several patient subgroups, including patients with diabetes, in-stent restenosis, multiple previous percutaneous transluminal coronary angioplasty (PTCA) procedures, longer lesion lengths, saphenous vein grafts, small vessel diameters, and minimum dose exposures < 8.00 Gy. Two-factor analysis of variance was used to test for an interaction between patient characteristics and treatment effect. RESULTS: In the treated group, late loss was particularly low in patients with diabetes (0.19 mm), in-stent restenosis (0.17 mm), reference vessel diameters < 3.0 mm (0.07 mm), and patients who received a minimum radiation dose to the entire adventitial border of at least 8.00 Gy. The loss index in each of these subgroups was similarly low at -0.02, 0.03, -0.02, and 0.03, respectively. By 2-factor analysis of variance, a significant interaction between subgroup characteristic and treatment effect (late loss) was found in patients with in-stent restenosis (p = 0.035), and patients receiving a minimum dose of 8.00 Gy to the adventitial border (p = 0.009). CONCLUSION: In this pilot study, patient characteristics associated with a more aggressive proliferative response to injury appeared to confer an enhanced response to radiotherapy. Furthermore, a dose threshold response to 192Ir was found with an enhanced response occurring when the entire circumference of the adventitial border was exposed to at least 8.00 Gy.

The role of ambient lighting in circadian disc shedding in the rod outer segment of the rat retina.

Rats raised from birth on a 7 A.M.:7 P.M. light cycle exhibited a circadian burst of shedding 1 1/2 hr after the scheduled onset of light. This rhythmic event persisted even after the animals had been placed in total darkness for up to 2 weeks. When animals were placed in constant light (LL) for more than 24 hr, the shedding peak was abolished. A period of darkness of at least 2 hr, ending at the normal time for light onset, was necessary for the production of a shedding burst. When animals were placed in altered lighting cycles, the shedding rhythm shifted accordingly, although the speed of this shift was greatest with large advances in the light cycle and slowest with small delays in the light cycle. Animals exposed to LL and then returned to the dark exhibited the original shedding rhythm, a phenomenon not affected when the optic nerves were severed. A shedding peak could be induced at a noncircadian time by exposing the animals to more than 20 hr of LL followed by 2 hr of darkness and 1 1/2 hr of light, although the magnitude of the shedding was related to the circadian time.

Evidence for both local and central regulation of rat rod outer segment disc shedding.

Rats entrained to a 7 A.M.:7 P.M. lighting cycle had one eye patched and then were placed in either constant light or in a 2 A.M.:2 P.M. lighting cycle. In both cases, the patched eyes maintained the original pattern of rod outer segment (ROS) disc shedding, whereas the open eyes responded to the ambient lighting conditions. When the optic nerves were severed at the optic chiasm, the shedding rhythm persisted, but it was no longer possible to shift the rhythm to a new lighting cycle. From these experiments we conclude that ROS disc shedding is regulated both by local oscillators within the orbit as well as by central elements.

Cardiopulmonary support.

Cardiopulmonary support (CPS) has been shown to be a useful addition to interventional cardiology when considering alternatives for high-risk patients. Cardiopulmonary support systems are capable of up to 6 liters/min output and can be used prophylactically to prevent hemodynamic collapse following balloon occlusions or acute vessel closure. The technique, supported angioplasty, results in reductions of preload and afterload and allows prolonged balloon inflations in critical coronary vessels. Although it provides excellent support for most high-risk patients, CPS is a technically challenging and expensive procedure associated with significant patient morbidity. Standby CPS patients are prepared for institution of CPS, but bypass is not actually initiated unless the patient sustains irreversible hemodynamic compromise. In this study, standby and prophylactic patients had comparable success and major complication rates, but procedural morbidity was more frequent in prophylactic patients. Further study will better define appropriate patient selection for standby versus prophylactic CPS.

Coronary stenting with angioscopic guidance.

Coronary angioscopy can directly visualize luminal morphology and stent architecture. This new technology may provide insights into the stent mechanism of action and help guide stent procedures. Visualization of the target vessel segment with a 4.5Fr angioscope was attempted before and/or after Palmaz-Schatz coronary stent implantation in 50 patients. The target vessel segment was successfully visualized in 48 patients (96%). In 24 patients, angioscopy was performed both after balloon angioplasty and then again after stenting. In 16 of these 24 patients a dissection was documented by angioscopy after balloon angioplasty, and in each patient the dissection was absent after stenting. Angioscopy influenced the clinical management of 18 (37.5%) patients. Clinical decisions directly influenced by angioscopy included intracoronary thrombolytic therapy for thrombus visualized angioscopically, which had been unsuspected by angiography (n = 7), withholding intracoronary thrombolytic therapy for patients with suspected thrombus not confirmed by angioscopy (n = 4), repeat angioplasty in patients in whom plaque was found to be bulging into the lumen at the stent articulation site (n = 4), additional stents placed when angioscopy revealed significant proximal or distal disease (n = 4), or an unsuspected gap between 2 tandem stents (n = 1). Coronary angioscopy safely visualized stented vessel segments in most patients. Angioscopic observations provided insights into the stent mechanism of action and, in some cases, influenced clinical management.