Long-term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT).

BACKGROUND: This long-term, multicenter, randomized, double-blind, placebo-controlled, 2 x 2 factorial, angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients. METHODS AND RESULTS: There were a total of 460 patients: 230 received simvastatin and 230, a simvastatin placebo, and 229 received enalapril and 231, an enalapril placebo (some subjects received both drugs and some received a double placebo). Mean baseline measurements were as follows: cholesterol level, 5.20 mmol/L; triglyceride level, 1.82 mmol/L; HDL, 0.99 mmol/L; and LDL, 3.36 mmol/L. Average follow-up was 47.8 months. Changes in quantitative coronary angiographic measures between simvastatin and placebo, respectively, were as follows: mean diameters, -0.07 versus -0.14 mm (P:=0.004); minimum diameters, -0.09 versus -0.16 mm (P:=0. 0001); and percent diameter stenosis, 1.67% versus 3.83% (P:=0.0003). These benefits were not observed in patients on enalapril when compared with placebo. No additional benefits were seen in the group receiving both drugs. Simvastatin patients had less need for percutaneous transluminal coronary angioplasty (8 versus 21 events; P:=0.020), and fewer enalapril patients experienced the combined end point of death/myocardial infarction/stroke (16 versus 30; P:=0.043) than their respective placebo patients. CONCLUSIONS: This trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients. The implications of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain, but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere.

Primary stenting versus balloon angioplasty in occluded coronary arteries: the Total Occlusion Study of Canada (TOSCA).

BACKGROUND: Balloon angioplasty (PTCA) of occluded coronary arteries is limited by high rates of restenosis and reocclusion. Although stenting improves results in anatomically simple occlusions, its effect on patency and clinical outcome in a broadly selected population with occluded coronary arteries is unknown. METHODS AND RESULTS: Eighteen centers randomized 410 patients with nonacute native coronary occlusions to PTCA or primary stenting with the heparin-coated Palmaz-Schatz stent. The primary end point, failure of sustained patency, was determined at 6-month angiography. Repeat target-vessel revascularization, adverse cardiovascular events, and angiographic restenosis (>50% diameter stenosis) constituted secondary end points. Sixty percent of patients had occlusions of >6 weeks' duration, baseline flow was TIMI grade 0 in 64%, and median treated segment length was 30.5 mm. With 95.6% angiographic follow-up, primary stenting resulted in a 44% reduction in failed patency (10.9% versus 19.5%, P=0.024) and a 45% reduction in clinically driven target-vessel revascularization at 6 months (15.4% versus 8.4%, P=0.03). The incidence of adverse cardiovascular events was similar for both strategies (PTCA, 23.6%; stent, 23.3%; P=NS). Stenting resulted in a larger mean 6-month minimum lumen dimension (1.48 versus 1.23 mm, P<0.01) and a reduced binary restenosis rate (55% versus 70%, P<0.01). CONCLUSIONS: Primary stenting of broadly selected nonacute coronary occlusions is superior to PTCA alone, improving late patency and reducing restenosis and target-vessel revascularization.

Real-time assessment of experimental arterial angioplasty with transvenous intravascular ultrasound.

Optimal evaluation of experimental angioplasty procedures would allow real-time simultaneous assessment during the procedure without direct manipulation of treated arterial segments. To assess the feasibility and utility of transvenous real-time intravascular ultrasound imaging during experimental angioplasty, 11 consecutive atherosclerotic iliac artery segments in rabbits were imaged before, during and after thermal or conventional perfusion balloon angioplasty. A 20-MHz intravascular ultrasound catheter was positioned in the adjacent vein, and images were correlated with data from quantitative angiography and histologic studies. Images suitable for analysis were obtained at all 11 sites. Arterial distension and recoil were observed during balloon inflation and deflation. Measurements of lumen diameter and cross-sectional area by intravascular ultrasound and angiography were closely correlated (r2 = 0.90, SEE = 0.2 mm, and r2 = 0.90, SEE = 0.8 mm2, respectively). Intimal dissections were identified in six segments by intravascular ultrasound and all were concordant with histologic findings. Thus, real-time transvenous ultrasound avoids manipulation of the treated artery, and is a feasible modality for dynamic quantitative and qualitative assessment of arterial interventions.

Mechanisms of balloon angioplasty and directional coronary atherectomy as assessed by intracoronary ultrasound.

OBJECTIVE: This study was designed to use intracoronary ultrasound imaging to elucidate the physical effects of balloon angioplasty and directional coronary atherectomy in vivo in humans. BACKGROUND: The proposed mechanisms of coronary artery interventions such as balloon angioplasty and directional atherectomy are based on animal studies or pathologic findings and these data may not be applicable to living patients. Intracoronary ultrasound findings correlate highly with pathologic results and may allow in vivo assessment of the mechanisms of such interventions in humans. METHODS: Intracoronary ultrasound imaging was performed in 45 patients after a successful coronary intervention (balloon angioplasty in 30, directional coronary atherectomy in 15). Ultrasound images obtained at the treatment site and at an adjacent angiographically normal references site were analyzed quantitatively for minimal lumen diameter, cross-sectional lumen area, are enclosed by the internal elastic lamina, plaque area (internal elastic lamina area--lumen area) and percent area stenosis (plaque area/internal elastic lamina area). Qualitative analysis included assessment of presence of dissection, plaque composition and plaque topography. RESULTS: The results of the two procedures were similar with respect to minimal lumen diameter (angioplasty 2.6 +/- 0.5 vs. atherectomy 2.6 +/- 0.3 mm, p = NS), lumen area (0.07 +/- 0.03 vs. 0.07 +/- 0.02 cm2, p = NS) and percent area stenosis (59 +/- 14% vs. 51 +/- 21%, p = NS). However, after angioplasty, the internal elastic lamina area was significantly larger at the treated site than at the reference site (delta = +0.03 +/- 0.04 cm2, p = 0.01). There was no significant difference between the two sites after atherectomy (delta = -0.01 +/- 0.05 cm2, p = NS). In addition, dissection was seen significantly more often after balloon angioplasty than after atherectomy (50% vs. 7%, p less than 0.01). The results were similar when stratified for plaque composition and morphology. These data were confirmed in six additional patients who underwent ultrasound imaging before and after the intervention. CONCLUSIONS: Thus, the improvement in lumen dimensions after coronary balloon angioplasty is a result of both vessel stretch, demonstrated by a larger internal elastic lamina area at the treated site, and dissection. Both vessel stretch and dissection are uncommon after atherectomy, a finding consistent with plaque removal as the major mechanism for improved lumen area after this procedure.

Intracoronary ultrasound predictors of adverse outcomes after coronary artery interventions.

OBJECTIVES: The purpose of this study was to determine the association between qualitative and quantitative lesion characteristics as assessed by intracoronary ultrasound imaging and adverse outcomes after coronary artery interventions. BACKGROUND: Restenosis and other adverse outcomes after coronary artery interventions may be difficult to predict from clinical or angiographic data. Intracoronary ultrasound imaging provides additional data that could prove useful. METHODS: Immediately after successful coronary artery interventions (angiographic residual stenosis < or = 50%), 69 patients underwent intracoronary ultrasound imaging. Images were assessed qualitatively for plaque composition and topography and for dissection. Quantitative data included measurement of minimal lumen diameter, lumen area, plaque area and percent area stenosis at the treatment and adjacent reference sites. Adverse outcome was defined as death, coronary bypass surgery, myocardial infarction or angiographic restenosis. RESULTS: Of the 69 patients, 1 died, 3 had bypass surgery and 1 had a myocardial infarction before planned 6-month repeat catheterization. Two patients were lost to follow-up study. Of the remaining 62 patients, 56 (90%) agreed to follow-up catheterization and 25 (45%) of the 56 had restenosis. Thus, 30 patients had an adverse outcome and 37 had no adverse event. The incidence of dissection detected by ultrasound imaging after an intervention was significantly greater in patients with than in those without a subsequent adverse event (63% vs. 35%, p < 0.05). The severity of dissection also appeared to be related to outcome (p < 0.05). Other qualitative and quantitative variables were not significantly different between the two patient groups. CONCLUSIONS: Dissection, as assessed by intracoronary ultrasound imaging after a coronary artery intervention, can identify patients at increased risk of subsequent adverse events. Additional studies are warranted to explore whether such imaging may allow modification of interventional procedures to improve outcome.

Cardiogenic shock complicating acute myocardial infarction--etiologies, management and outcome: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: This SHOCK Study report seeks to provide an overview of patients with cardiogenic shock (CS) complicating acute myocardial infarction (MI) and the outcome with various treatments. The outcome of patients undergoing revascularization in the SHOCK Trial Registry and SHOCK Trial are compared. BACKGROUND: Cardiogenic shock is the leading cause of death in patients hospitalized for acute MI. The randomized SHOCK Trial reported improved six-month survival with early revascularization. METHODS: Patients with CS complicating acute MI who were not enrolled in the concurrent randomized trial were registered. Patient characteristics were recorded as were procedures and vital status at hospital discharge. RESULTS: Between April 1993 and August 1997, 1,190 patients with CS were registered and 232 were randomized in the SHOCK Trial. Predominant left ventricular failure (78.5%) was most common, with isolated right ventricular shock in 2.8%, severe mitral regurgitation in 6.9%, ventricular septal rupture in 3.9% and tamponade in 1.4%. In-hospital Registry mortality was 60%, with ventricular septal rupture associated with a significantly higher mortality (87.3%) than all other categories (p < 0.01). The risk profile and mortality were lower for Registry patients who were managed with thrombolytic therapy and/or intra-aortic balloon counter-pulsation, coronary angiography, angioplasty and/or coronary artery bypass surgery. After adjusting for these differences, the extent to which survival was improved with early revascularization was similar to that observed in the randomized SHOCK Trial. CONCLUSIONS: In this prospective Registry the etiology of CS was a mechanical complication in 12%. The similarity of the beneficial treatment effect in patients undergoing early revascularization in the SHOCK Trial Registry and SHOCK Trial provides strong support for the generalizability of the SHOCK Trial results.

Implications of the timing of onset of cardiogenic shock after acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: We sought to examine the implications of the timing of onset of cardiogenic shock (CS) after acute myocardial infarction (MI). BACKGROUND: Little information is available about the relationships between timing, clinical substrate, management and outcomes of shock. METHODS: The multinational SHOCK Trial Registry enrolled MI patients with CS from 1993 to 1997. Cardiogenic shock was predominantly attributable to left ventricular (LV) failure in 815 Registry patients for whom temporal data were available. We examined factors related to the timing of shock onset and the relation of temporal onset to in-hospital outcomes. RESULTS: Overall, shock developed a median of 6.2 h after MI symptom onset. Shock onset varied by culprit artery: left main, median 1.7 h; right, 3.5 h; circumflex, 3.9 h; left anterior descending (LAD), 11.0 h; saphenous vein graft, 10.9 h (p = 0.025). Early shock (< 24 h) occurred in 74.1% and was associated with chest pain at shock onset, ST-segment elevation in two or more leads, multiple infarct locations, inferior MI, left main disease and smoking. Late shock (> or = 24 h) was associated with recurrent ischemia, Q waves in two or more leads and LAD culprit vessel. Mortality was higher in patients with early versus late shock (62.6% vs. 53.6%, p = 0.022). CONCLUSIONS: Shock onset after acute MI occurred within 24 h in 74% of the patients with predominant LV failure. Mortality was slightly higher in patients developing shock early rather than later. Many factors influence when shock develops, which has implications for its management.

Cardiogenic shock due to acute severe mitral regurgitation complicating acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we use emergently revascularize Occluded Coronaries in cardiogenic shocK?

OBJECTIVES: Our objective was to define the outcomes of patients with cardiogenic shock (CS) due to severe mitral regurgitation (MR) complicating acute myocardial infarction (AMI). BACKGROUND: Methods for early identification and optimal treatment of such patients have not been defined. METHODS: The SHOCK Trial Registry enrolled 1,190 patients with CS complicating AMI. We compared 1) the cohort with severe mitral regurgitation (MR, n = 98) to the cohort with predominant left ventricular failure (LVF, n = 879), and 2) the MR patients who underwent valve surgery (n = 43) to those who did not (n = 51). RESULTS: Shock developed early after MI in both the MR (median 12.8 h) and LVF (median 6.2 h) cohorts. The MR patients were more often female (52% vs. 37%, p = 0.004) and less likely to have ST elevation at shock diagnosis (41% vs. 63%, p < 0.001). The MR index MI was more frequently inferior (55% vs. 44%, p = 0.039) or posterior (32% vs. 17%, p = 0.002) than that of LVF and much less frequently anterior (34% vs. 59%, p < 0.001). Despite having higher mean LVEF (0.37 vs. 0.30, p = 0.001) the MR cohort had similar in-hospital mortality (55% vs. 61%, p = 0.277). The majority of MR patients did not undergo mitral valve surgery. Those undergoing surgery exhibited higher mean LVEF than those not undergoing surgery; nevertheless, 39% died in hospital. CONCLUSIONS: The data highlight opportunities for early identification and intervention to potentially decrease the devastating mortality and morbidity of severe post-myocardial infarction MR.

Does ticlopidine reduce reocclusion and other adverse events after successful balloon angioplasty of occluded coronary arteries? Results from the Total Occlusion Study of Canada (TOSCA).

OBJECTIVES: Ticlopidine reduces stent thrombosis and other adverse events among patients receiving coronary stents. Whether ticlopidine is beneficial after balloon angioplasty is unknown. Our purpose was to compare the clinical outcome of patients undergoing balloon angioplasty treated with both aspirin and ticlopidine versus aspirin alone. METHODS AND RESULTS: We performed a databank analysis of the Total Occlusion Study of Canada (TOSCA), a randomized trial with angiographic follow-up comparing the frequency of reocclusion after angioplasty of a subtotal or total coronary occlusion in patients receiving >/=1 heparin-coated Palmaz-Schatz stent versus balloon angioplasty alone. In TOSCA, 102 patients undergoing balloon angioplasty were treated with both aspirin and ticlopidine (generally for 15-30 days) and 94 were treated with aspirin alone, by physician preference. After 6 months, failure to sustain patency (less than Thrombolysis in Myocardial Infarction [TIMI] grade 3 flow on follow-up angiography) occurred in 23% of patients on ticlopidine and aspirin versus 16% of patients on aspirin alone (P =.21); the frequency of target vessel revascularization was also similar in the 2 groups (32% vs 25%, P =.27). Myocardial infarction was infrequent in both groups (2.0% vs 1.1%, respectively, P not significant). Patients treated with aspirin and ticlopidine had more adverse angiographic and procedural characteristics, including longer lesions and treatment lengths. Multivariate analysis to adjust for these and other differences failed to reveal a benefit of ticlopidine in maintaining patency and reducing adverse clinical events. CONCLUSIONS: After balloon angioplasty of a subtotal or total coronary occlusion, no reduction in adverse events was observed among patients in whom ticlopidine was added to aspirin, even after adjustment for clinical and lesion characteristics.

Unrecognized left main coronary artery disease in patients undergoing interventional procedures.

Selective, coronary arteriographic, catheter-based, intravascular ultrasound images were obtained to determine the presence and extent of angiographically undetected or underestimated left main (LM) coronary arterial narrowing in patients receiving coronary interventional therapy. Coronary arteriograms were determined to be either normal or abnormal by visual inspection. Abnormal arteriograms were digitized and quantitated using a semiautomated edge-detection algorithm. Thirty-eight patients receiving percutaneous treatment of stenoses in the left coronary artery system were studied. Optimal LM coronary angiograms were obtained in 2 views, and intravascular ultrasound images were obtained after the coronary interventional procedure. Intravascular ultrasound detected plaque in 24 of 27 angiographically normal LM arteries (89%), whereas narrowing was observed in 11 of 11 angiographically abnormal LM arteries (100%). Eight of 38 patients (21%) had > 40% area stenosis by intravascular ultrasound. In patients with angiographic disease, there was no correlation between quantitative angiographic and ultrasound percent area stenosis (r = 0.12; p = 0.72; SEE 19%). The median plaque area was not different between angiographically normal (0.05 cm2; 0.03, 0.08 [25th, 75th percentile]) and abnormal (0.06 cm2; 0.03, 0.1) patients. The median percent area stenosis in arteriographically normal subjects (26%; 14, 32%) was less than that in abnormal ones (37%; 20, 46%) (p = 0.03). Unrecognized LM disease is widespread and often underestimated in patients with normal LM angiograms undergoing interventional procedures. Plaque area is similar for angiographically normal and insignificantly abnormal vessels. This study suggests that intravascular ultrasound overcomes the limitations of silhouette imaging and can be a clinically useful, adjunctive method to evaluate LM coronary artery disease.

Co-morbidity data in outcomes research: are clinical data derived from administrative databases a reliable alternative to chart review?

Evaluation of co-morbidity data is essential in health outcomes research. Co-morbidity data derived from administrative databases has been criticized for lacking the accuracy required for clinical research. We compared co-morbidity data derived from a Canadian provincial hospitalization database with chart review in 817 adults treated with a percutaneous coronary intervention at a single tertiary care hospital between 1994 and 1995. While the administrative database tended to under-estimate the prevalence of some co-morbid conditions, the agreement between chart review and administrative data was good to very good for most conditions. Asymptomatic conditions were noted to have lower levels of agreement. Multivariate risk models for all-cause mortality constructed from both data sources were almost identical, suggesting minimal misclassification. The results indicate that clinical data abstracted from most Canadian hospitalization databases can provide reliable information regarding baseline co-morbid conditions believed to influence survival in a population undergoing percutaneous coronary interventions.

Early and intermediate term clinical outcome after multiple coronary stenting.

OBJECTIVE: To examine the immediate and intermediate term clinical outcome of multiple coronary stenting. DESIGN: Consecutive patients were prospectively entered on a dedicated database. Follow up information was obtained from outpatient and telephone interviews with patients and family physicians. SETTING: A tertiary referral centre. PATIENTS: 140 consecutive patients underwent multiple coronary stenting between April 1994 and November 1996. Most patients had unstable coronary syndromes. MAIN OUTCOME MEASURES: Death, cerebrovascular accidents, myocardial infarction (MI), coronary artery bypass surgery (CABG), and repeat angioplasty (PTCA). RESULTS: The angiographic success rate was 100% and the clinical procedural success rate 93%. The mean (SD) follow up was 11.9 (7.2) months (range 2-32). The mean (SD) number of stents per patient was 2.4 (0.7). The mean (SD) number of lesions treated per patient was 1.4 (0.6). There were four in-hospital deaths (2.9%) and five patients (3.6%) had an MI before hospital discharge. All in-hospital deaths occurred in patients presenting with an acute MI and cardiogenic shock. Three patients (2.2%) had a late MI. One patient with stent thrombosis underwent emergency CABG. Three patients (2.2%) underwent late CABG. Eight patients (5.7%) had a repeat PTCA. Eighty three patients (61.5%) were asymptomatic at follow up and 121 (86.4%) were free from major clinical events. CONCLUSION: In an era of increased operator experience, high pressure stent deployment, and reduced anticoagulation with antiplatelet treatment alone, multiple coronary stenting may be performed with a high procedural success rate and good intermediate term outcome.

Antiplatelet therapy alone is safe and effective after coronary stenting: observations of a transition in practice.

OBJECTIVE: To evaluate the safety and efficacy of transition in practice after coronary stenting to antiplatelet therapy alone compared with anticoagulation with warfarin. DESIGN: Retrospective analysis of coronary stent management in a tertiary Canadian centre. PATIENTS: A total of 136 consecutive patients (146 lesions) were analyzed who underwent Palmaz-Schatz coronary stenting over a 15-month period and were treated with anticoagulation with warfarin (56 patients) or antiplatelet therapy alone with ticlopidine and acetylsalicylic acid (80 patients) during the transition in poststenting therapy in the authors' practice. Treatment was continued for 30 days in both groups. High pressure stent deployment was used in the majority of cases (greater than 90%), and use of intravascular ultrasound was infrequent (less than 12%). MAIN RESULTS: At 30 days, there were no clinical manifestations of stent thrombosis, coronary artery bypass surgery or repeat angioplasty in either group. One death occurred in the antiplatelet group. Periprocedural non-Q wave myocardial infarction occurred in two patients in the antiplatelet group and in one patient in the warfarin group. There was a significantly higher incidence of vascular complications in the warfarin group than in the antiplatelet group (14.3% versus 2.5%, respectively, P = 0.04). The length of hospital stay was significantly shorter in the antiplatelet group than in the warfarin group (3.0 +/- 1.8 versus 6.7 +/- 2.6 days, respectively, P < 0.001). CONCLUSIONS: Reduced anticoagulation with antiplatelet therapy alone after coronary stenting, despite infrequent use of intravascular ultrasound, is an effective and safe strategy with a low rate of vascular complications, a relatively short hospital stay and a low incidence of clinical manifestations of stent thrombosis.

An open design, multicentre, randomized trial of percutaneous transluminal coronary angioplasty versus stenting, with a heparin-coated stent, of totally occluded coronary arteries: rationale, trial design and baseline patient characteristics. Total Occlusion Study of Canada (TOSCA) Investigators.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) of totally occluded coronary arteries is performed in a variety of clinical settings and for a variety of indications. Most commonly it is performed for relief of symptoms of myocardial ischemia. Studies have also suggested that PTCA of occluded arteries beyond the acute phase of myocardial infarction may improve left ventricular function even in the absence of objective evidence of ischemia. One of the major limitations of total occlusion PTCA is a high rate of reocclusion, reported to be as high as 40%. Recently, small studies have suggested that stenting may improve the long term outcome after PTCA of total coronary occlusions. OBJECTIVES: To determine in a prospective, randomized trial whether long term patency and clinical outcome following successful PTCA of a totally occluded coronary can be improved by the use of of a heparin-coated stent. PATIENTS AND METHODS: Subjects were randomly assigned to one of two strategies once the guide wire had crossed the occluded segment of the target artery: PTCA alone, or PTCA followed by insertion of Palmaz-Shatz heparin-coated stent(s). Randomization was stratified according to duration of the coronary occlusion: six weeks or less, and more than six weeks. The primary end-point is failure of sustained patency (Thrombolysis in Myocardial Infarction [TIMI] flow grade less than 3) at six months. Secondary end-points are change in minimal luminal diameter, target vessel revascularization at one year, cardiovascular events at one year, and change in global and regional left ventricular function. BASELINE CHARACTERISTICS: All 410 patients have been randomly assigned to the PTCA alone (n = 208) or PTCA plus stent (n = 202) group. Mean age was 58 +/- 11 years and 18% were female. Prior myocardial infarction had been documented in 67% of patients. The duration of occlusion was six weeks or less in 40% and more than six weeks in 60% of patients. In 64% of patients TIMI flow was grade 0 and in 36% it was grade 1. STUDY IMPLICATIONS: The trial will demonstrate whether the use of a heparin-bonded stent can improve long term patency and clinical outcome in patients undergoing clinically indicated PTCA of totally occluded coronary arteries. If a significant reduction in reocclusion and clinical events is demonstrated, the Total Occlusion Study of Canada (TOSCA) would offer a more effective long term revascularization strategy in future trials testing the open artery hypothesis.

Angiogenic gene therapy in patients with nonrevascularizable ischemic heart disease: a phase 2 randomized, controlled trial of AdVEGF(121) (AdVEGF121) versus maximum medical treatment.

The demonstration that angiogenic growth factors can stimulate new blood vessel growth and restore perfusion in animal models of myocardial ischemia has led to the development of strategies designed for the local production of angiogenic growth factors in patients who are not candidates for conventional revascularization. The results of recent clinical trials of proangiogenesis gene therapy have been disappointing; however, significant limitations in experimental design, in particular in gene transfer strategies, preclude drawing definitive conclusions. In the REVASC study cardiac gene transfer was optimized by direct intramyocardial delivery of a replication-deficient adenovirus-containing vascular endothelial growth factor (AdVEGF121, 4 x 10(10) particle units (p.u.)). Sixty-seven patients with severe angina due to coronary artery disease and no conventional options for revascularization were randomized to AdVEGF121 gene transfer via mini-thoracotomy or continuation of maximal medical treatment. Exercise time to 1 mm ST-segment depression, the predefined primary end-point analysis, was significantly increased in the AdVEGF121 group compared to control at 26 weeks (P=0.026), but not at 12 weeks. As well, total exercise duration and time to moderate angina at weeks 12 and 26, and in angina symptoms as measured by the Canadian Cardiovascular Society Angina Class and Seattle Angina Questionnaire were all improved by VEGF gene transfer (all P-values at 12 and 26 weeks < or =0.001). However, if anything the results of nuclear perfusion imaging favored the control group, although the AdVEGF121 group achieved higher workloads. Overall there was no significant difference in adverse events between the two groups, despite the fact that procedure-related events were seen only in the thoracotomy group. Therefore, administration of AdVEGF121 by direct intramyocardial injections resulted in objective improvement in exercise-induced ischemia in patients with refractory ischemic heart disease.

Double Marker ACX II: a new balloon catheter for coronary stent delivery.

We report our initial experience using the Double Marker ACX II for intracoronary stent deployment in 22 patients, 10 of whom were elective stents and 12 of whom were stented for complications following failed coronary angioplasty. The overall success rate was 95 percent. This dilatation catheter offers advantages which include accurate stent deployment with a double marker system, the option of using a delivery sheath, and the ability to deliver multiple stents with the same balloon catheter.

Thermal-perfusion balloon coronary angioplasty: in vivo evaluation.

The goal of this study was to develop and test a new radio frequency thermal balloon system to allow longer balloon inflations at lower temperature levels than have been used with standard (laser) thermal balloon angioplasty. Radio frequency thermal capabilities were combined with perfusion balloon technology, creating a thermal-perfusion balloon catheter system for prolonged thermal inflations. Twenty-five dogs underwent thermal-perfusion angioplasty at 37 degrees, 60 degrees, or 80 degrees C for 1.5, 5, or 15 minutes with angiographic and morphologic assessments at 24 hours (n = 17) or 4-6 weeks later (n = 8). Treated segments and side branches remained patent. No coronary spasm, occlusive thrombus, or ischemic myocardial infarction occurred. Histologic extent of thermal injury in treated segments was proportional to treatment duration. Thus the thermal-perfusion balloon angioplasty system may be safely applied in canine coronary arteries. Integrating thermal and perfusion technologies provides prolonged treatment duration at moderate temperatures without excessive tissue damage.

Results of percutaneous transluminal coronary angioplasty in unstable angina and non-Q-wave myocardial infarction. Observations from the TIMI IIIB Trial.

BACKGROUND: This report describes the results of percutaneous transluminal coronary angioplasty (PTCA) in the Thrombolysis in Myocardial Ischemia (TIMI) IIIB Investigation. METHODS AND RESULTS: PTCA was performed before hospital discharge in 444 of 1473 patients with either unstable angina pectoris or non-Q-wave myocardial infarction (NQWMI) enrolled in TIMI IIIB. Angiographic success was observed in 96.1% of patients. For the entire cohort, the cumulative incidences of death and infarction at 1 year were 2.0% and 8.2%, respectively. The periprocedural incidence of myocardial infarction was 2.7%; emergency coronary bypass surgery, 1.4%; and death, 0.5%. By 1 year of follow-up, 122 patients (28.0%, Kaplan-Meier) had an additional revascularization procedure, 75 (61.5%) had PTCA only, 30 (24.6%) had coronary bypass surgery only, and 17 (13.9%) had both procedures. The results of PTCA were not improved by routine pretreatment with intravenous tissue plasminogen activator (TPA). Periprocedural myocardial infarction was more common among patients receiving TPA than placebo (odds ratio [OR], 2.19; P = .03) and among those with unstable angina than those with NQWMI (OR, 15.5; P = .007). No difference in outcome was observed when patients were analyzed according to age (OR, 1.06; P = .092) or sex (OR, 1.54; P = .51). Variables predictive of poor outcome were PTCA within the first 24 hours of enrollment, PTCA site being the left anterior descending coronary artery, and unsuccessful angiography. CONCLUSIONS: In TIMI IIIB, PTCA was performed for patients with unstable angina and NQWMI with a very high rate of angiographic success and a low incidence of complications. By 1 year, repeat revascularization was performed in 28.0% of patients. Routine pretreatment with thrombolysis did not enhance outcome.

Multiple coronary stenting in unstable angina: early and late clinical outcomes.

We examined clinical outcomes in 110 consecutive patients with unstable angina who underwent multiple coronary stenting over a 32-mo period. The main outcome measures were death, stroke, myocardial infarction, bypass surgery, and repeat angioplasty. The angiographic success rate was 100%, and the procedural success rate was 96%. There were no in-hospital deaths and five (4.5%) patients had a myocardial infarction prior to discharge. There were four (3.6%) stent thromboses with one (0.9%) patient requiring urgent bypass surgery and two (1.8%) requiring repeat angioplasty. At late follow-up (11.9+/-7.1 mo), there was (0.9%) death and three patients (2.8%) suffered myocardial infarction. Three (2.8%) patients underwent late bypass surgery and five (4.6%) had a repeat angioplasty. At follow-up, 86% of patients were event free. We conclude that multiple coronary stenting in unstable angina may be performed with a high procedural success rate and good long-term outcome.

Suture closure of femoral arterial puncture sites after coronary angioplasty followed by same-day discharge.

BACKGROUND: The purpose of this study was to determine whether immediate suture closure of 8F femoral arterial puncture sites can facilitate same-day discharge after coronary angioplasty. METHODS AND RESULTS: After coronary angioplasty, 100 patients were randomly assigned to immediate sheath removal with the double-suture Prostar-Plus device or delayed sheath removal with application of a c-clamp. After suture closure, mobilization at 4 hours after sheath removal and discharge 4 hours later were planned. Patients treated with the c-clamp had sheaths removed 4 hours after percutaneous transluminal coronary angioplasty, were mobilized 6 hours later, and discharged the following day. Patients were assessed for groin complications at 8, 24, and 72 hours. Overall, patients who received suture closure were mobilized at 7.1 +/- 5.3 hours and discharged 11. 15 +/- 6.22 hours after sheath removal versus 15.49 +/- 3.9 hours and 21.9 +/- 3.8 hours for patients with the c-clamp (P <.001). Initial failure of the suture device occurred in 5 patients, with 1 requiring surgery for an entrapped device. After the procedure, patients with suture closure more frequently had an ooze of blood (55% vs 24%, P <.001) and a trend to more overt external bleeding (10% vs 2%, P = not significant). Hematomas were reported by 20% of patients in both groups at 72 hours. Overall, patients preferred the suture closure method of sheath removal when assessed by a simple questionnaire. An economic analysis by cost minimization demonstrated potential hospital cost saving. CONCLUSIONS: Suture closure of 8F arterial puncture sites can facilitate early mobilization and same-day discharge and is considered acceptable by more patients compared with application of the c-clamp. There is potential to realize cost savings with a strategy of same-day discharge.