Long-term clinical outcome and predictors of major adverse cardiac events after percutaneous interventions on saphenous vein grafts.

OBJECTIVES: The purpose of this study was to examine the long-term clinical outcome after percutaneous intervention of saphenous vein grafts (SVG) and to identify the predictors of major adverse cardiac events (MACE). BACKGROUND: Percutaneous interventions of SVGs have been associated with more procedural complications and higher restenosis rates compared with interventions on native vessels. METHODS: From 1993 to 1997, 1,062 patients underwent percutaneous intervention on 1,142 SVG lesions. Procedural, in-hospital and long-term clinical outcomes were recorded in a database and analyzed. RESULTS: In-hospital MACE occurred in 137 patients (13%) including death (8%), Q-wave myocardial infarction (MI) (2%) and coronary artery bypass surgery (3%). Late MACE occurred in 565 patients (54%) including death (9%), Q-wave MI (9%) and target vessel revascularization (36%). Any MACE occurred in 457 (43%) patients. Follow-up was available in 1,056 (99%) patients at 3 +/- 1 year. Univariate predictors were restenotic lesion (odds ratio [OR]: 2.47, confidence interval [CI]: 1.13 to 3.85, p = 0.0003), unstable angina (OR: 1.99, CI: 1.27 to 2.91, p = 0.04) and congestive heart failure (CHF) (OR: 1.97, CI: 1.14 to 3.24, p = 0.02) for in-hospital MACE, and peripheral vascular disease (PVD) (OR: 2.18, CI: 1.34 to 3.44, p = 0.002), intra-aortic balloon pump placement (OR: 2.08, CI: 1.13 to 3.85, p = 0.02) and previous MI (OR: 1.97, CI: 1.14 to 3.25, p = 0.007) for late MACE. Independent multivariate predictors for late MACE were restenotic lesion (relative risk [RR] 1.33, p = 0.02), PVD (RR: 1.31, p = 0.01), CHF (RR: 1.42, p = 0.01) and multiple stents (RR: 1.47, p = 0.004). Angiographic follow-up was available for 422 patients. Angiographic restenosis occurred in 122 (29%) of stented SVGs and 181 (43%) of nonstented SVGs (p = 0.04). Stent implantation did not confer a survival benefit. CONCLUSIONS: Despite the use of new interventional devices, SVG interventions are associated with significant morbidity and mortality; SVG stenting is not associated with better three-year event-free survival. This may be due to progressive disease at nonstented sites.

Comparison of self-expanding and balloon-expandable stents for the reduction of restenosis.

To compare the efficacy of self-expanding (SE) and balloon-expandable (BE) stents in native coronary arteries, we randomly assigned 1,096 patients with new and restenotic lesions to receive either device. Baseline demographics and coronary angiographic characteristics were similar in the 2 groups. The incidence of major adverse cardiac events including death, myocardial infarction, bypass surgery, and repeat intervention was similar for both groups at 1 month (2.9% vs 3.1% for SE vs BE, respectively) and at 9 months (19.3% vs 20.1%, SE vs BE respectively). In a subgroup of patients who underwent follow-up angiography (n = 250), the binary restenosis rates (24.2% vs 18.7%, p = 0.30), late loss (0.98 vs 94 mm, p = 0.60), and loss index (0.55 vs 55, p = 0.95) were not significantly different for both groups. In 62 patients who underwent intravascular ultrasound examination (IVUS), there was a trend toward a lower incidence of edge tears in the SE group (6% vs 23%, p = 0.06). Follow-up IVUS analysis showed that the minimum stent area of the SE stent increased by 33% at 6 months, whereas no change occurred in the BE stents; this was accompanied by a greater degree of intimal proliferation in the SE stents compared with BE stents (3.1 +/- 2.0 vs 1.7 +/- 1.7 mm(2)). Thus, the SE stents had similar clinical and angiographic outcomes in patients with lesions in native coronary arteries.

Coronary angioplasty and Rotablator atherectomy trial (CARAT): immediate and late results of a prospective multicenter randomized trial.

Mechanical rotational atherectomy with the Rotablator is widely used for percutaneous coronary revascularization, but the ideal debulking strategy remains unknown. The purpose of this study was to compare the immediate and late results after Rotablator using two treatment strategies: Large burrs (burr/artery ratio of >0.7) to achieve maximal debulking (lesion debulking strategy) or small burrs (burr/artery ratio < or = 0.7) to modify lesion compliance (lesion modification strategy). Two hundred twenty-two patients at six centers were prospectively enrolled in this study and randomly assigned to large (n = 104 patients with 118 lesions) or small (n = 118 patients with 136 lesions) burrs. The primary endpoint was final diameter stenosis at the end of the procedure, and secondary endpoints included inhospital angiographic and clinical complications, and target lesion revascularization at 6 months. Baseline demographic and angiographic characteristics were similar. There were no differences in procedural success, the extent of immediate lumen enlargement, inhospital ischemic complications, or late target vessel revascularization. However, compared with small burrs, patients randomized to large burrs were more likely to experience serious angiographic complications (5.1% vs. 12.7%, P < 0.05) immediately after atherectomy. This study suggests that a routine lesion modification strategy employing small burrs (burr/artery ratio < or = 0.7) achieves similar immediate lumen enlargement and late target vessel revascularization compared with a more aggressive debulking strategy (burr/artery ratio >0.7), but with fewer angiographic complications.

Randomized comparison of GR-II stent and Palmaz-Schatz stent for elective treatment of coronary stenoses.

BACKGROUND: This prospective multicenter randomized clinical trial was designed to evaluate the long-term angiographic and clinical outcomes of elective treatment with the GR-II stent compared with the Palmaz-Schatz (PS) stent in patients with coronary stenoses. METHODS AND RESULTS: Seven hundred fifty-five patients with myocardial ischemia and de novo native coronary stenoses in 3- to 4-mm vessels were randomly assigned to the PS (375 patients) or the GR-II stent (380 patients). The primary end point was 12-month target lesion revascularization (TLR)-free survival. Angiography was performed at baseline and at follow-up in the first 300 consecutive patients to assess the frequency of angiographic restenosis. Procedure success was 98.5% for the GR-II stent and 99.4% for the PS stent (P:=0.19). At 30 days, patients assigned to the GR-II stent had a higher stent thrombosis rate (3.9% versus 0.3% for PS stent, P:<0.001) and TLR rate (3.9% versus 0.5% for PS stent, P:<0.001). The GR-II group had a higher follow-up restenosis frequency (47.3% versus 20.6% for the PS group, P:<0.001) and a lower 12-month TLR-free survival rate (71.7% versus 83.9% for the PS group, P:<0. 001). Multivariate logistic regression analysis identified a smaller final stent minimal lumen diameter (odds ratio [OR] 2.49, 95% CI 1. 56 to 3.98; P:<0.001), diabetes mellitus (OR 2.14, 95% CI 1.42 to 3. 22; P:<0.001), and use of the GR-II stent (OR 1.78, 95% CI 1.20 to 2. 64; P:<0.01) as independent determinants of 12-month TLR. CONCLUSIONS: On the basis of these long-term follow-up data, we conclude that use of the GR-II stent should be limited to the acute treatment of abrupt or threatened closure after failed conventional balloon angioplasty procedures.

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.

Recurrent ventricular fibrillation in a marathon runner during exercise testing.

We report a case of a marathon runner who presented with chest tightness, ST-segment depression, and ventricular fibrillation following treadmill exercise testing. At cardiac catheterization, the patient was found to have an isolated lesion in the left anterior descending (LAD) artery that was hemodynamically insignificant by accepted angiographic and coronary flow reserve standards. Ventricular fibrillation was thought to be idiopathic, and an implantable cardioverter defibrillator was placed. Chest pain and ST-segment depression followed by ventricular fibrillation was reproduced during follow-up treadmill testing, prompting reconsideration of the original diagnostic hypothesis. A coronary stent was deployed in the LAD artery. The patient has been asymptomatic and arrhythmia free during follow-up treadmill testing and recreational running.

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.

Immediate and long-term results of elective and emergent percutaneous interventions on protected and unprotected severely narrowed left main coronary arteries.

Percutaneous revascularization of protected and unprotected left main coronary arteries is associated with acceptable immediate results, but there are significant long-term consequences, including the need for repeat percutaneous intervention (10%), myocardial infarction (7.5%), coronary artery bypass surgery (7%), and death (38%), despite the elective or emergent nature of the procedure.

Effect of reperfusion on biventricular function and survival after right ventricular infarction.

BACKGROUND: Although the salutary effects of reperfusion in patients with left ventricular infarction are well documented, the benefits in patients with acute right ventricular infarction are less clear. METHODS: To determine whether primary angioplasty improves right ventricular function and the clinical outcome in patients with right ventricular infarction, we performed echocardiographic studies before and after angioplasty in 53 patients with acute right ventricular infarction. RESULTS: Complete reperfusion, defined as normal flow in the right main coronary artery and its major right ventricular branches, was achieved in 41 patients (77 percent), leading to prompt and striking recovery of right ventricular function (mean [+/-SE] score for free-wall motion, 3.0+/-0.1 at base line and 1.4+/-0.1 at three days; P<0.001). Twelve patients (23 percent) had unsuccessful reperfusion, defined as the failure to restore right ventricular branch flow, with or without patency of the right main coronary artery. Unsuccessful reperfusion was associated with lack of recovery of right ventricular function (score for free-wall motion, 3.2+/-0.2 at base line and 3.0+/-0.9 at three days; P= 0.55), as well as persistent hypotension and low cardiac output (in 83 percent of the patients, vs. 12 percent of those with successful reperfusion; P=0.002) and a high mortality rate (58 percent, vs. 2 percent for those with successful reperfusion; P=0.001). CONCLUSIONS: In patients with right ventricular infarction, complete reperfusion of the right coronary artery by angioplasty results in the dramatic recovery of right ventricular performance and an excellent clinical outcome. In contrast, unsuccessful reperfusion is associated with impaired recovery of right ventricular function, persistent hemodynamic compromise, and a high mortality rate.

Intraoperative angiography to assess graft patency after minimally invasive coronary bypass.

BACKGROUND: Intraoperative angiography was performed to confirm graft patency immediately after minimally invasive coronary bypass operations. METHODS: In 26 patients who had internal mammary artery grafting, intraoperative coronary angiography was performed with a portable digital fluoroscope. RESULTS: High-resolution angiograms were obtained in all cases. Angiography documented vasospasm of the graft or native vessel in 9 patients (graft in 3, native in 2, graft and native in 4 others), which responded promptly to intracoronary vasodilators in all. Angiography identified technically unsuspected and clinically silent fixed stenoses (>50%) in 11 patients, attributable to graft kinking in 2, anastomotic obstruction in 6 (total occlusion in 4), and stenosis of the left anterior descending artery just distal to the anastomosis in three cases (total occlusion in one). In 9 of 11 patients, fixed stenoses were sufficiently severe to warrant intraoperative intervention by surgical revision (n = 5) or angioplasty via the graft (n = 4). CONCLUSIONS: Intraoperative angiography after minimally invasive coronary artery bypass operations can immediately identify dynamic and fixed obstructions and facilitate their prompt treatment, thereby ensuring that each patient leaves the operating room with an optimal surgical result.

Problems in the evaluation of new devices for coronary intervention: what have we learned since 1989?

The objectives of this study are to review the problems associated with the evaluation of new devices, the progress made in that evaluation process since 1989, and the role played by the New Approaches to Coronary Intervention (NACI) registry. In 1988-1989, the first wave of new coronary devices (stents, atherectomy, laser catheters) were entering clinical investigation. It seemed unlikely that the small manufacturer-run registries used to gain approval for earlier balloon catheters would be adequate to evaluate the host of complex new devices, each of which might be used for a restricted set of anatomic indications. Moreover, the wide range of arbitrary definitions then in use for fundamental outcomes (such as success, complication, and restenosis), effectively precluded meaningful device-to-device comparisons. Against this backdrop, the NACI registry was formed with National Heart, Lung, and Blood Institute funding to provide an independent and standardized evaluation of the first 8 new devices under evaluation in the United States, across the broad range of their application. The registry employed a unique modular form set to track the sequence of events during complex cases in which serial new devices and balloon angioplasty might be used, either in a planned way, or an unplanned way (to treat complications or suboptimal results). Outcomes were subjected to standardized criteria for (1) the reason for device use (planned, unplanned); (2) success (device, lesion, and procedural success); (3) complications (a) major (death, Q-wave myocardial infarction, and emergency coronary artery bypass grafting); or (b) other (groin complications, non-wave myocardial infarction, etc.); and (4) clinical restenosis (any subsequent revascularization, target lesion revascularization). Separate funding for an angiographic core laboratory was obtained in 1992, which analyzed 3,936 (88.9%) of the 4,429 films obtained on patients enrolled between November 1990 and March 1994. The NACI registry has addressed a broad range of problems inherent in the evaluation of new devices for coronary intervention. Whereas the approval process has moved progressively towards randomized clinical trials (and away from registries), the NACI registry offers a unique view of current practice, outside the narrow scope of the limited number of randomized trials that have been performed to date. This article shows, however, that we have learned about more than the devices themselves since 1989-we have also learned about the importance of knowing the reason for device use, using precise definitions of endpoint variables, understanding the financial and reimbursement ramifications of new device trials, and upholding strict investigator ethics during the conduct of such evaluations.

Directional coronary atherectomy (DCA): a report from the New Approaches to Coronary Intervention (NACI) registry.

Directional coronary atherectomy (DCA) with the Simpson coronary atherocath seeks to debulk rather than simply displace obstructive tissue and is a means of enlarging the stenotic coronary lumen. This report from the New Approaches to Coronary Intervention (NACI) registry describes the experience of 1,196 patients who underwent DCA as the sole treatment for either native vessel or vein graft lesions. Device success (post-DCA residual stenosis <50% and > or =20% improvement) was achieved in 87.8%, with a lesion success rate (postprocedural residual stenosis <50% and > or =20% improvement) of 94.0%. The mean resultant stenosis after all interventions (by core laboratory) was 19%. Significant in-hospital complications occurred in 2.8% of patients with DCA attempts, including death 0.6%, Q-wave myocardial infarction (MI) 1.5%, and emergent coronary artery bypass graft surgery (CABG) 2.8%. At 1-year follow-up, cumulative mortality was 3.6%, with repeat revascularization in 28% (repeat percutaneous transluminal coronary angioplasty, 20.1%; CABG, 10.6%). This reflected percutaneous or surgical revascularization of the original lesion (target lesion revascularization) in 22.6% of patients. Subgroup analysis showed a lower lesion success rate and an increased complication rate for unplanned use, vein graft treatment, and treatment of a de novo (vs a restenotic) lesion. Multivariate analysis shows that diabetes mellitus, unstable angina, treatment of a restenotic lesion, and greater residual stenosis after the initial procedure were independent predictors of the composite endpoint of death/Q-wave MI/target lesion revascularization by 1-year follow-up. Among these generally favorable acute and 1-year results, the NACI directional atherectomy data confirm the "bigger is better" hypothesis: that lesions with a lower residual stenosis after a successful procedure had significantly fewer target lesion revascularizations between 30 days and 1 year, with no increase in major adverse events.

Predictors of acute and long-term outcome with transluminal extraction atherectomy: the New Approaches to Coronary Intervention (NACI) registry.

The New Approaches to Coronary Intervention (NACI) registry was established to define the role of new coronary devices in overcoming the limitations of balloon angioplasty. The purpose of the present study was to evaluate the acute and long-term efficacy of the transluminal extraction catheter (TEC) device utilizing data from the NACI registry and identify clinical and anatomic patient subsets who may benefit from this device. From 1990-1994, >4,300 patients from 39 clinical sites enrolled consecutive patients treated with one of the 7 new devices to the NACI registry. The study population consists of 331 patients (385 lesions) treated with planned TEC as the sole new device. Of these patients, 243 (292 lesions) were treated for saphenous vein graft (SVG) disease and 88 (93 lesions) for native disease. Patients undergoing SVG treatment were older and more likely to be male. They had lower ventricular function, more unstable angina, and a higher incidence of congestive heart failure. Multivessel disease was more prevalent in the SVG cohort, as was evidence of thrombus before treatment. Although device success was achieved in 50% of SVG lesions and 41% of native lesions, lesion success was achieved in 90% and 78%, respectively, after adjunctive balloon angioplasty, and procedure success rates were 86% and 79%, respectively. The in-hospital major complication (death/Q-wave myocardial infarction/emergency coronary artery bypass graft [CABG] surgery) rate was higher in the SVG cohort (6.2% vs 2.3%), mainly due to higher mortality rate (5.3% vs 1.1%). Multivariate analysis showed that SVG was not an independent predictor for either an in-hospital major complication or clinical failure. The risk factors for major in-hospital complications were history of congestive heart failure (odds ratio = 3.17) and thrombus (odds ratio = 3.36). For clinical failure the risk factors were diabetes (odds ratio = 1.88), thrombus (odds ratio = 2.08), and calcium (odds ratio = 3.09). One-year rates of death, Q-wave myocardial infarction, or any repeat revascularization were 51% in the SVG cohort and 41% in the native cohort. Following adjustment, patients treated for SVG disease did not have a higher risk when compared with those treated for native disease. The factors significantly associated with this composite event at 1 year are male (relative risk = 1.41), patients with history of congestive heart failure (relative risk = 1.56), and total occlusions (relative risk = 1.52). This study shows that for both SVG and native cohorts, device success rates were low with TEC alone, but acceptable lesion success rates were achieved when adjunctive PTCA was used. In-hospital as well as 1-year major complications were higher in the SVG cohort. However, after adjusting for other risk factors, SVG attempt was not significantly associated with either in-hospital or 1-year events.

Acute and long-term outcome after Palmaz-Schatz stenting: analysis from the New Approaches to Coronary Intervention (NACI) registry.

The randomized Stent Restenosis Study (STRESS) and Belgium Netherlands Stent (Benestent) trials established that elective use of Palmaz-Schatz stents (PSSs) in native coronary arteries with de novo lesions is associated with increased procedural success and reduced restenosis. However there are other clinical indications for which stents are commonly used (unplanned use, vein grafts, restenosis lesions) that are not addressed in these studies. From 1990-1992, 688 lesions in 628 patients were treated with PSSs in the New Approaches to Coronary Intervention (NACI) registry. Angiographic core laboratory readings were available for 543 patients (595 lesions, of which 106 were stented for unplanned indications, 239 were in saphenous vein bypass grafts, and 296 were previously treated). The cohort of patients in whom stents were placed for unplanned indications had more women, current smokers, and had a higher incidence of recent myocardial infarction (MI). Patients who underwent stenting of saphenous vein grafts were older, had a higher incidence of diabetes mellitus, unstable angina, prior MI, and congestive heart failure. Lesion success was similar in all cohorts (98%), but procedural success was significantly higher for planned stenting (96% vs 87%; p < 0.01). Predictors of adverse events in-hospital were presence of a significant left main stenosis and stenting for unplanned indication. The incidence of target lesion revascularization by 30 days was significantly higher for patients undergoing unplanned stenting due to a higher risk for stent thrombosis. Recent MI, stenting in native lesion, and small postprocedural minimum lumen diameter independently predicted target lesion revascularization at 30 days. Independent predictors of death, Q-wave myocardial infarction, or target lesion revascularization at 1 year included severe concomitant disease, high risk for surgery, left main disease, stenting in the left main coronary artery, and low postprocedure minimum lumen diameter.

Tracheobronchial Wallstents for degenerated saphenous vein bypass grafts.

The tracheobronchial Wallstent was employed as an endoluminal prosthesis in degenerated saphenous vein bypass grafts in three patients. This Wallstent has unique characteristics that make it potentially useful in patients with vein graft disease.

Incidence and angiographic predictors of side branch occlusion following high-pressure intracoronary stenting.

We evaluated the incidence, angiographic predictors, and clinical outcome of side branch occlusion (SBO) following high-pressure intracoronary stenting in 175 patients. All stent implants during a 7-month period were reviewed for the incidence of major (>1 mm) SBO. Side branches were further characterized based on side branch and index lesion morphology. Clinical events (death, myocardial infarction, and target vessel revascularization rates) were determined at 9 months. A total of 175 patients (182 lesions) had 224 major side branches covered by intracoronary stents. Of these, 43 (19%) occluded. Most SBOs (29 of 43 [67%]) occurred after poststent dilation using high-pressure inflations (15.3 +/- 3.3 atmospheres). No clinical characteristics correlated with SBO. By multivariate analysis, those side branches with >50% ostial narrowing that arose from within or just beyond the diseased portion of the parent vessel (threatened side branch morphologies) were a powerful angiographic predictor of SBO (odds ratio 40, 95% confidence interval, 14 to 130, p <0.0001). At 9-month follow-up there was no difference in combined clinical events between those patients with and without SBO. These data demonstrate that side branches with ostial stenoses in continuity with diseased parent lesions were at risk of occlusion following stenting. SBO, however, was not associated with adverse clinical outcome. These findings lend support to plaque shift ("snow plow effect") as the mechanism behind SBO following stent placement.

Monitoring platelet glycoprotein IIb/IIIa-fibrin interaction with tissue factor-activated thromboelastography.

Computerized thromboelastography (TEG) was used to study platelet glycoprotein IIb/IIIa function, characterize the consequences of the interaction between polymerizing fibrin and activated platelets, and establish a quantitative assay of platelet function. The ability of platelets to augment the shear elastic modulus of blood clots was measured by TEG under conditions of maximal platelet activation during ex vivo clot formation accelerated by recombinant human tissue factor (TF). Under these conditions, platelets significantly enhance clot strength eightfold (relative to platelet-free fibrin clots). This effect, inhibited by cytochalasin D and c7E3 Fab, appears to be dependent on the transmission of platelet contractile force to fibrin, through glycoprotein IIb/IIIa receptors. The c7E3 Fab dose response of TF-TEG clot strength is identical to results with platelet aggregation induced by the thrombin receptor agonist peptide (50% inhibitory concentration (IC50 = 3.6 microg/ml); adenosine diphosphate-induced aggregation is easier to inhibit (IC50 = 1.2 microg/ml). The results obtained with this system are reproducible (coefficient of variation for clot strength 4%; intraclass correlation coefficient 0.96). As a clinical assay, TF-triggered computerized TEG is easy to perform at the bedside, provides on-line results within 30 minutes, and may offer advantages over conventional measures of platelet function.