Heparin after percutaneous intervention (HAPI): a prospective multicenter randomized trial of three heparin regimens after successful coronary intervention.

OBJECTIVES: The purpose of this study was to determine the incidence of bleeding, vascular, and ischemic complications using three different heparin regimens after successful intervention. BACKGROUND: The ideal dose and duration of heparin infusion after successful coronary intervention is unknown. METHODS: Patients were randomized to one of three heparin strategies after coronary intervention: Group 1 (n = 157 patients) received prolonged (12 to 24 h) heparin infusion followed by sheath removal; Group 2 (n = 120 patients) underwent early removal of sheaths, followed by reinstitution of heparin infusion for 12 to 18 h; Group 3 (n = 137 patients) did not receive any further heparin after intervention with early sheath removal. The primary end point of the study was the combined incidence of in-hospital bleeding and vascular events. Secondary end points included in-hospital ischemic events, length of stay, cost and one-month outcome. RESULTS: After successful coronary intervention, 414 patients were randomized. Unstable angina or postinfarction angina was present in 83% of patients before intervention. The combined incidence of bleeding and vascular events was 21% in Group 1, 14% in Group 2 and 8% in Group 3 (p = 0.01). The overall incidence of in-hospital ischemic complications was 2.2%; there were no differences between groups. Length of hospital stay was shorter (p = 0.033) and adjusted hospital cost was lower (p < 0.001) for Group 3. At 30 days, the incidence of delayed cardiac and vascular events was similar for all three groups. CONCLUSIONS: Heparin infusion after successful coronary intervention is associated with more minor bleeding and vascular injury, prolonged length of stay and increased cost. In-hospital and one-month ischemic events rarely occur after successful intervention, irrespective of heparin use. Routine postprocedure heparin is not recommended, even in patients who present with unstable ischemic syndromes.

Coronary artery fistula after cardiac transplantation.

A cardiac transplant recipient with multiple coronary artery fistulae draining into the right ventricle is described. These fistulae presumably resulted from repeated endomyocardial biopsies. The diagnosis of coronary artery fistulae was made at the annual coronary arteriography. The magnitude of the shunt remained small over eight years of follow-up.

Giant coronary artery pseudoaneurysm causing pulmonary artery obstruction: a rare complication of coronary bypass surgery--a case report.

The authors report the diagnosis and successful management of a 57-year-old man with right ventricular outflow tract obstruction from a large pseudoaneurysm of the left anterior descending coronary artery 5 years after he had undergone redo coronary artery bypass grafting.

Inhibitors of the platelet GP IIb-IIIa function in the treatment of acute coronary syndromes.

Platelet activation is a critical mechanism in acute coronary artery syndromes and ischemic complications of percutaneous coronary revascularization. Thrombin and platelet inhibition are the current mainstays of therapy for these problems. Inhibitors of platelet GP IIb-IIIa, the final common pathway of platelet aggregation, have recently undergone clinical evaluation as therapeutics for acute ischemic syndromes, and as adjuvants for percutaneous revascularization. The results of these prospective, controlled trials, and current evaluations of GP IIb-IIIa inhibitors are summarized in this review.

Intravenous cocaine induces platelet activation in the conscious dog.

BACKGROUND: Cocaine consumption has been associated with thrombosis of coronary and peripheral arteries. Since cocaine has been found to induce platelet activation in vitro, we sought to establish whether cocaine induced platelet activation in vivo. METHODS AND RESULTS: Chronically instrumented, conscious dogs were infused with cocaine (1 mg/kg), norepinephrine (0.2 to 0.4 mg/kg), or saline intravenously over 1 minute. Activated canine platelets were identified in whole blood collected from an indwelling aortic catheter by flow cytometric detection of the binding of a monoclonal antibody directed against the activation-dependent antigen P-selectin. Infusion of cocaine resulted in an elevation of mean arterial pressure (91 +/- 3 to 128 +/- 7 mm Hg [P < .01]) and heart rate (87 +/- 9 to 125 +/- 11 beats per minute [P < .01]). A similar change (P = NS) in mean arterial pressure followed norepinephrine infusion (100 +/- 5 to 137 +/- 13 mm Hg [P < .04]), whereas saline infusion had no effect. Cocaine resulted in a substantial but delayed increase in platelet P-selectin expression (14 +/- 7% [P < .08], 31 +/- 12% [P < .04], and 55 +/- 22% [P < .04] at 17, 22, and 27 minutes after drug infusion, respectively). The magnitude of this increase was similar to that found in blood treated ex vivo with the agonists ADP or PAF (23 +/- 7% and 53 +/- 15%, respectively). No significant increase in P-selectin expression was detected in the blood of animals that received norepinephrine or saline. Serum cocaine concentrations were highest immediately after infusion (538 +/- 55 ng/mL at 2 minutes) but declined rapidly (185 +/- 22 and 110 +/- 25 ng/mL at 17 and 32 minutes after infusion); in contrast, the increase in benzoylecgonine concentrations was delayed (from < 25 ng/mL in all but one animal [34 ng/mL] at 2 minutes to 46 +/- 4 and 71 +/- 11 ng/mL at 17 and 32 minutes, respectively, after infusion). CONCLUSIONS: Intravenous cocaine induces activation of individual circulating platelets; this effect is not reproduced by infusion of norepinephrine at doses sufficient to exert similar hemodynamic effects. The delay in detection of activated platelets after treatment with cocaine may result from the adhesion and subsequent detachment of activated platelets; alternatively, cocaine metabolites, rather than the drug itself, may induce platelet activation.

Endoluminal stenting of a subclavian artery stenosis to treat ischemia in the distribution of a patent left internal mammary graft.

Subclavian artery stenosis is a rare cause of recurrent myocardial ischemia in patients who have undergone left internal mammary-coronary artery bypass grafting. A patient with this syndrome was successfully treated by placement of Palmaz biliary stents in the left subclavian artery. Angiographic and hemodynamic evidence of restricted subclavian flow resolved following stenting, as did the patient's unstable angina syndrome. Endoluminal stenting of the proximal subclavian artery for the treatment of coronary-subclavian steal can be performed safely and provides an alternative to other forms of surgical or percutaneous (PTCA, directional atherectomy) revascularization for treatment of this disorder.

Elevation of the creatine kinase myocardial isoform following otherwise successful directional coronary atherectomy and stenting.

Moderate elevation of creatine kinase (CK) MB isoform is common following otherwise successful percutaneous coronary revascularization, and is frequently interpreted as evidence of a non-Q-wave myocardial infarction. It is not clear, however, whether elevation of CK MB isoform carries sufficient adverse clinical impact to be categorized as a "major" complication. We therefore explored the incidence and clinical consequence of elevation of CK MB isoform in a consecutive series of 565 patients who had otherwise successful directional coronary atherectomy (n = 274) or stenting (n = 291), and were followed for a mean of 2 years. Of this cohort, 11.5% had postprocedure elevation of the CK MB isoform above normal (10 IU/liter). These patients tended to be older and to have undergone atherectomy of a de novo lesion with adverse morphology (thrombus, calcification, eccentricity). Patients with elevation of CK MB isoform following otherwise successful revascularization generally showed no adverse long-term sequelae (death, recurrent myocardial infarction, repeat revascularization) compared with patients without elevation of CK MB isoform. Only 2.3% of the patients who had CK MB isoform release > 50 IU/liter demonstrated a trend (p = 0.08) toward decreased late survival, compared with patients without CK MB isoform elevation. While minor CK MB isoform elevation is common (11.5%) after successful coronary stenting or directional atherectomy, it generally has no adverse clinical consequences, and should not be considered a major complication.(ABSTRACT TRUNCATED AT 250 WORDS)

Is 40% to 70% diameter narrowing at the site of previous stenting or directional coronary atherectomy clinically significant?

Traditional binary definitions of coronary restenosis based on 6-month continuous angiographic measurements (e.g., > 50% diameter stenosis) may give confusing results for lesions whose late percent stenosis falls near the arbitrary threshold. To determine the long-term clinical consequences of such lesions, the overall correlation between follow-up percent stenosis and the performance of subsequent ischemia-driven target vessel revascularization (triggered by significant angina or a positive exercise study result, or both) was examined in 443 consecutive lesions treated with directional coronary atherectomy or Palmaz-Schatz coronary stenting. Follow-up angiograms (available in 355 lesions, 82%) were stratified into 3 groups: severe late stenosis (> 70% stenosis, n = 59), moderate late stenosis (40% to 70% stenosis, n = 72), and minimal late stenosis (< 40% stenosis, n = 224). With an average clinical follow-up of 933 +/- 394 days, 92% of lesions in the "severe late stenosis" group were treated with ischemia-driven target vessel revascularization, compared with 0% of the lesions in the "minimal late stenosis" group. Ischemia-driven target vessel revascularization was performed in 38% of patients in the "moderate late stenosis" group. However, patients in this group who did not undergo revascularization (despite the fact that 43% of them had a late stenosis of > 50%) showed a similarly favorable long-term clinical outcome to patients with a minimal late stenosis. These results support a strategy of conservative management for the 20% of patients who have a moderate (40% to 70%) late stenosis after stenting or atherectomy, but do not have evidence of ischemia.

Incidence and treatment of 'no-reflow' after percutaneous coronary intervention.

BACKGROUND: Profound reduction in antegrade epicardial coronary flow with concomitant ischemia is seen occasionally during percutaneous coronary intervention despite the absence of evident vessel dissection, obstruction, or distal vessel embolic cutoff. In a prior small series of cases, this "no-reflow" phenomenon appeared to be promptly reversed by the intra-coronary administration of verapamil. METHODS AND RESULTS: To further understand the prevalence of this syndrome and its responsiveness to the proposed therapy, we reviewed 1919 percutaneous interventions performed between January 1991 and April 1993. During the study period, 39 patients (2.0%) met our criteria for no reflow, 37 of whom were treated with intracoronary nitroglycerin followed by intracoronary verapamil and 2 of whom received intracoronary nitroglycerin alone. An additional 16 patients (0.8%) were given verapamil as part of the management of a flow-limiting dissection or distal embolus (mechanical obstruction). Intracoronary verapamil (50 to 900 micrograms, total dose) improved TIMI flow grade in 89% of no-reflow patients and markedly reduced the number of cineframes between contrast injection and opacification of a selected distal landmark (from 91 +/- 56 to 38 +/- 21 frames, P < .001). By contrast, only 19% of patients with epicardial mechanical obstruction showed improvement in TIMI flow grade after verapamil, with minimal reduction in frames to opacification (from 107 +/- 42 to 101 +/- 69, P = .73). CONCLUSIONS: The no-reflow phenomenon--reduction in distal flow without apparent dissection or distal embolization--occurs in 2% of coronary interventions. It generally responds promptly to intracoronary verapamil administration, suggesting that distal microvascular spasm may be its etiology.

Effect of prior coronary restenosis on the risk of subsequent restenosis after stent placement or directional atherectomy.

Lesions that have developed restenosis after a prior intervention may be more likely to develop restenosis after subsequent percutaneous interventions. To determine if this is an independent effect, the clinical characteristics and immediate angiographic outcomes of 179 prior restenosis lesions were compared with those of 254 primary lesions after stenting or directional atherectomy. Six-month angiographic follow-up was obtained for 79% of successfully treated lesions. Univariable and multivariable logistic regression was used to determine how binary restenosis (defined as > or = 50% diameter stenosis at follow-up) was influenced by postprocedure luminal diameter, left anterior descending artery location, diabetes mellitus, as well as prior restenosis. At 6-month follow-up, prior restenosis lesions had a significantly smaller late diameter (1.77 vs 2.18 mm, p < 0.001), more absolute late loss (1.35 vs 1.14 mm, p = 0.051), a higher loss index (0.58 vs 0.45, p < 0.02), and a higher binary restenosis rate (37.3% vs 24.4%, p = 0.01). Whereas univariable analysis revealed that left anterior descending artery location, diabetes mellitus, postprocedure luminal diameter < 3.1 mm, and prior restenosis were each strong predictors of binary restenosis (all p < 0.02), multivariable analysis showed that after adjustment for left anterior descending artery location, diabetes, and postprocedure luminal diameter, prior restenosis was no longer an independent predictor of restenosis (odds ratio 1.57, 95% confidence interval 0.95-2.60, p = 0.073). In conclusion, although prior restenosis lesions do show more restenosis than primary lesions, much of this effect is due to preselection of a population enriched in other known factors that predispose to restenosis.

Palmaz-Schatz stenting for treatment of focal vein graft stenosis: immediate results and long-term outcome.

OBJECTIVES: This study aimed to evaluate the effectiveness of Palmaz-Schatz stenting for the treatment of saphenous vein graft stenoses. BACKGROUND: Failure of saphenous vein grafts is a common cause of recurrent ischemia after coronary bypass surgery. A second bypass surgery carries more risk than the initial procedure, and balloon angioplasty of vein grafts has yielded disappointing results. It has been hoped that stenting might offer a better treatment option. METHODS: We examined the results of stent placement in 200 saphenous bypass graft lesions consecutively treated with either coronary (n = 146) or biliary (n = 54) Palmaz-Schatz stents. Immediate outcome and clinical follow-up (median 15.5 months) were examined in all patients. To document angiographic outcome, a second angiography was performed at 3 to 6 months for the first 120 consecutively stented lesions and was successfully obtained for 94 (78%). RESULTS: The mean graft age (+/- SD) was 8.7 +/- 4 years. Stent placement was successful in 197 (98.5%) of 200 lesions, reducing the mean diameter stenosis from 74 +/- 14% to 1 +/- 15%. In 164 procedures, there was one in-hospital death (0.6%), no emergency bypass operations and no Q wave myocardial infarctions. There was one acute stent thrombosis (0.6%) but no subacute thromboses. Vascular repair was required after 14 procedures (8.5%), with transfusion in 23 additional cases (14%). Angiographic restenosis (diameter stenosis > or = 50%) at 3- to 6-month follow-up was 17% (95% confidence interval 9% to 25%). By Kaplan-Meier estimates, however, the 2-year second revascularization rate was 49%, reflecting the predominant revascularization performed to treat progressive disease at other sites because failure at the stented site occurred in only 22% of lesions. CONCLUSIONS: Stenting resulted in excellent immediate and long-term angiographic results in this group of focally diseased, older saphenous vein grafts. Despite the high immediate success and very low (17%) angiographic restenosis rate at 6 months, approximately one half of these patients required further revascularization in the following 2 years, mainly because of disease progression at other sites.

Balloon postdilation can safely improve the results of successful (but suboptimal) directional coronary atherectomy.

This study investigates whether adjunctive balloon angioplasty can be safely used to improve acute results in cases where directional coronary atherectomy alone has provided a successful (but suboptimal) outcome. Between October 1, 1990, and October 1, 1992, directional coronary atherectomy was performed successfully in 198 of 228 lesions. Individual operators believed that most acute results were satisfactory after atherectomy alone (group I, n = 115) with a minimal lumen diameter that increased from 0.82 +/- 0.45 to 3.21 +/- 0.65 mm after atherectomy, for an acute gain in lumen diameter of 2.39 +/- 0.73 mm and a residual stenosis of 6 +/- 13%. In 42% of lesions (group II, n = 83), however, results were considered suboptimal after atherectomy alone, with a minimal lumen diameter that increased from 0.85 +/- 0.45 to 2.83 +/- 0.64 mm, a smaller acute gain of 1.96 +/- 0.72 mm, and a mean residual stenosis of 17 +/- 14% (although all residual stenoses were < 50%, 19% had a residual stenosis > 30%). Adjunctive balloon angioplasty in these group II lesions provided an additional gain of 0.34 +/- 0.38 mm, bringing the total acute gain for group II lesions to 2.32 +/- 0.78 mm and the residual stenosis to 9 +/- 13%, similar to that of group I patients who underwent atherectomy alone. This strategy resulted in a 7 +/- 13% overall residual stenosis for the study population, with no higher incidence of periprocedural complications or adverse late clinical outcomes in group II patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Activation of human platelets by cocaine.

BACKGROUND: Cocaine ingestion has been associated with thrombosis of coronary as well as peripheral arteries, but the mechanism by which cocaine promotes thrombus formation is unknown. Accordingly, we determined whether cocaine activates human platelets by flow cytometric analysis of whole blood to which cocaine was added. METHODS AND RESULTS: Activated platelets were detected by "two-color" flow cytometric analysis of the binding of fluorescently labeled antibodies directed against either platelet-associated fibrinogen or P-selectin, which are found on the surface of platelets only after stimulation. Platelets were distinguished from other constituents of whole blood by their ability to bind an anti-glycoprotein Ib antibody bound to both activated and resting platelets. Incubation of whole blood with cocaine, in concentrations of 10 microM to 13 mM, induced significant increases in both platelet-associated fibrinogen (range of increase, 45 +/- 12% to 125 +/- 40%) and P-selectin expression (36 +/- 15% to 112 +/- 24%). In platelets suspended in either buffer or plasma, however, P-selectin expression was detected only at the highest cocaine concentration (85 +/- 13% increase in plasma and 59 +/- 7% in buffer). Neither aspirin nor the ADP scavenger apyrase inhibited cocaine-induced P-selectin expression. Cocaine inhibited the uptake of 14C-radiolabeled serotonin by platelets (IC50, 8.7 microM). P-selectin expression and fibrinogen binding were found after the addition of cocaine alone to blood taken from some but not all donors; however, platelet activation in response to submaximal concentrations of the agonists ADP or epinephrine was enhanced by a low concentration of cocaine added to blood from every donor. CONCLUSIONS: Cocaine, in concentrations similar to those found clinically, induces activation of individual platelets studied in whole blood from some but not all donors, and platelet response to physiological agonists is enhanced by cocaine. Thus, cocaine-induced platelet activation may contribute to thrombosis following cocaine ingestion.

Coronary arteriovenous fistula presenting as congestive heart failure.

Coronary arteriovenous fistulae are rare, but can be of hemodynamic significance. We report a circumflex-coronary sinus fistula in an elderly man which was associated with a loud continuous murmur and congestive heart failure. Noninvasive evaluation, including transesophageal echocardiography and magnetic resonance imaging, suggested the diagnosis. Angiographic diagnosis of concomitant atherosclerotic coronary disease may be difficult, and can require postoperative study.