Intracoronary high-dose bolus tirofiban administration during complex coronary interventions: A United States-based case series.

The GP IIb/IIIa inhibitors (GPIs) rapidly provide therapeutic levels of platelet aggregation inhibition and serve as adjunct pharmacotherapy to oral P2Y12 inhibitors that exhibit a significant delay in onset of action for patients with Acute Coronary Syndrome (ACS). Intracoronary (IC) administration of the high dose bolus (HDB) tirofiban has not been extensively studied. Compared to intravenous delivery, IC administration can lead to higher local drug concentration and, therefore, provide instantaneous disruption of platelet aggregation in the culprit vessel. This report describes the successful resolution of thrombus using IC HDB tirofiban in 7 high-risk coronary interventions with complications such as recurrent thrombosis and cardiogenic shock in ACS patients. This report represents the first case series of IC HDB tirofiban performed in North America and suggests that IC HDB tirofiban may represent an effective and safe strategy to achieve rapid thrombus resolution in ACS patients.

Prospective, head-to-head comparison of quantitative coronary angiography, quantitative computed tomography angiography, and intravascular ultrasound for the prediction of hemodynamic significance in intermediate and severe lesions, using fractional flow reserve as reference standard (from the ATLANTA I and II Study).

The objective of this study was to compare the diagnostic accuracy of quantitative coronary angiography (QCA), coronary computed tomography angiography (CTA), and intravascular ultrasound (IVUS) with fractional flow reserve (FFR) measurements. Eighty-five lesions (40% to 99% diameter stenosis) in 85 patients were prospectively interrogated by QCA, CTA, IVUS, and FFR. Minimal lumen diameter (MLD), percent diameter stenosis (%DS), minimal lumen area (MLA), and percent area stenosis (%AS) were measured. Correlation, receiver operating characteristic analysis, kappa statistics, and multivariable logistic regression was used to assess relation between anatomic measurements and FFR. Average age was 61.3 ± 7.8; 62% were men. QCA-derived mean %DS was 55.3% ± 19.5%; mean FFR 0.81 ± 0.17; 27% had FFR ≤0.75. QCA had the strongest correlation, followed by CTA and then IVUS for MLD (r = 0.67, 0.47, and 0.29, respectively) and for %DS (r = -0.63, -0.52, and -0.22, respectively); QCA-derived MLD had area under the curve of 0.96, with 95% sensitivity and 82% specificity. Cut-point, area under the curve, sensitivity, and specificity for CTA-MLA and IVUS-MLA were 3.11 mm(2), 0.86, 81%, and 81% and 2.68 mm(2), 0.75, 70%, and 80%. In multivariable analysis for each modality, MLD on QCA (odds ratio [OR]: 0.002), %AS on CTA (OR: 1.09) and MLA on IVUS (OR: 0.28) remained independent predictors. In conclusion, in intermediate-to-severe lesions, QCA-, CTA-, and IVUS-derived quantitative anatomic measurements correlated with FFR. CTA-derived cut-points were similar to respective measurements on QCA and IVUS and had similar or better diagnostic performance compared with IVUS.

Prospective validation that vulnerable plaque associated with major adverse outcomes have larger plaque volume, less dense calcium, and more non-calcified plaque by quantitative, three-dimensional measurements using intravascular ultrasound with radiofrequency backscatter analysis : results from the ATLANTA I Study.

Whether quantitative, two-dimensional, and three-dimensional plaque measurements by intravascular ultrasound with radiofrequency backscatter (IVUS/VH) are different between intermediate lesions with or without major adverse cardiovascular events (MACE) is unknown. IVUS/VH-derived parameters were compared in 60 patients with an intermediate coronary lesion (40-70 %) between lesions that did or did not result in MACE over 12 months. IVUS/VH measurements were done at the site of the minimal lumen area (MLA) and on a per-plaque basis, defined by 40 % plaque burden. Pre-specified, adjudicated MACE events occurred in 5 of 60 patients (8.3 %). MACE lesions had larger plaque burden (65 % vs. 53 %, p = 0.004), less dense calcium (6.6 % vs. 14.7 %, p = 0.05), and more non-calcified plaque, mostly fibrofatty kind (17.6 % vs. 10 %, p = 0.02). Intermediate coronary lesions associated with MACE at 12 months have more plaque, less dense calcium, and more non-calcified plaque, particularly fibrofatty tissue by IVUS/VH.

Prospective validation of standardized, 3-dimensional, quantitative coronary computed tomographic plaque measurements using radiofrequency backscatter intravascular ultrasound as reference standard in intermediate coronary arterial lesions: results from the ATLANTA (assessment of tissue characteristics, lesion morphology, and hemodynamics by angiography with fractional flow reserve, intravascular ultrasound and virtual histology, and noninvasive computed tomography in atherosclerotic plaques) I study.

OBJECTIVES: This study sought to determine the accuracy of 3-dimensional, quantitative measurements of coronary plaque by computed tomography angiography (CTA) against intravascular ultrasound with radiofrequency backscatter analysis (IVUS/VH). BACKGROUND: Quantitative, 3-dimensional coronary CTA plaque measurements have not been validated against IVUS/VH. METHODS: Sixty patients in a prospective study underwent coronary X-ray angiography, IVUS/VH, and coronary CTA. Plaque geometry and composition was quantified after spatial coregistration on segmental and slice-by-slice bases. Correlation, mean difference, and limits of agreement were determined. RESULTS: There was significant correlation for all pre-specified parameters by segmental and slice-by-slice analyses (r = 0.41 to 0.84; all p < 0.001). On a segmental basis, CTA underestimated minimal lumen diameter by 21% and overestimated diameter stenosis by 39%. Minimal lumen area was overestimated on CTA by 27% but area stenosis was only underestimated by 5%. Mean difference in noncalcified plaque volume and percent and calcified plaque volume and percent were 38%, -22%, 104%, and 64%. On a slice-by-slice basis, lumen, vessel, noncalcified-, and calcified-plaque areas were overestimated on CTA by 22%, 19%, 44%, and 88%. There was significant correlation for percentage of atheroma volume (0.52 vs. 0.54; r = 0.51; p < 0.001). Compositional analysis suggested that high-density noncalcified plaque on CTA best correlated with fibrous tissue and low-density noncalcified plaque correlated with necrotic core plus fibrofatty tissue by IVUS/VH. CONCLUSIONS: This is the first validation that standardized, 3-dimensional, quantitative measurements of coronary plaque correlate with IVUS/VH. Mean differences are small, whereas limits of agreement are wide. Low-density noncalcified plaque correlates with necrotic core plus fibrofatty tissue on IVUS/VH.

Validation of claims-based diagnostic and procedure codes for cardiovascular and gastrointestinal serious adverse events in a commercially-insured population.

PURPOSE: To validate administrative claims codes with medical chart review for myocardial infarction (MI), ischemic stroke, and severe upper gastrointestinal (UGI) bleed events in a large, commercially-insured US population. METHODS: These validation studies were part of a larger study examining the risk of MI, ischemic stroke, and severe UGI bleeds in patients receiving a new prescription of selective cyclooxygenase (COX)-2 inhibitors (coxibs) and non-over-the-counter (OTC) non-steroidal anti-inflammatory drugs (NSAIDs), between 1 July 2002 and 30 September 2004. Patients from the study cohort and other health plan members from the HealthCore Integrated Research Database(SM) (HIRD) experiencing these events were selected for these studies. The positive predictive value (PPV) of each of the claims code algorithms, using medical chart review as the gold standard, was calculated. RESULTS: Two hundred charts per event were abstracted. The PPV for MI was 88.4% (177/200; 95%CI, 83.2-92.5%); PPV for ischemic stroke was 87.4% (175/200; 95%CI, 82.0-91.7%); PPV for severe UGI bleed was 56.5% (109/193; 95%CI, 49.2-63.6%). Refining the ischemic stroke claims algorithm resulted in a PPV of 95.5% (95%CI, 91.0-98.2%); refining the claims algorithm for severe UGI bleed resulted in a PPV of 87.8% (95%CI, 78.7-94.0%). CONCLUSION: The results suggest that, for certain adverse events, claims data can serve as the basis for pharmacoepidemiology research and drug safety surveillance in the US.

A novel percutaneous mechanical biventricular bridge to recovery in severe cardiac allograft rejection.

We describe the case of a 36-year-old man with acute cardiac transplant rejection bridged to recovery using simultaneous Impella 2.5 and TandemHeart percutaneous support devices. The patient underwent orthotopic cardiac transplantation 2 years earlier, and presented to our hospital with allograft failure 7 days after non-compliance with tacrolimus. Because of persistent cardiogenic shock despite intra-aortic balloon and inotropic support, we implanted an Impella 2.5 percutaneous assist device for left ventricular support. Persistent right ventricular dysfunction necessitated insertion of a TandemHeart for right ventricular support. After a course of intravenous solumedrol and anti-thymocyte globulin, both the Impella and TandemHeart devices were successfully weaned and removed. Nine months later, his left ventricular ejection fraction had stabilized from 10% to 55%.

Vascular brachytherapy using a beta emitter source in diabetic patients with in-stent restenosis: angiographic and clinical outcomes.

PURPOSE: The management of diabetic patients with restenosis after percutaneous coronary intervention remains a significant challenge. Diabetic patients remain at significant risk of restenosis despite stent implantation. This retrospective analysis was performed to determine the extent to which vascular brachytherapy improves late clinical and angiographic outcomes in diabetic patients compared to conventional therapy and compared to patients' nondiabetic counterparts. METHODS: Pooled data from two studies (START [Stents and Radiation Trial] and START-40 trials) of patients (204 diabetic, 477 nondiabetic) receiving vascular brachytherapy (VBT) with a (90)Sr/(90)Y source after conventional percutaneous coronary intervention for in-stent restenosis comprise the study population. The radiation delivery system used in both studies was the Beta-Cath system. The prescribed dose at 2 mm from the centerline of the source axis was 18.4 Gy or 23 Gy, depending on vessel diameter. The reference vessel diameter, minimal lumen diameter, and percent diameter stenosis were measured before the intervention, at the conclusion of the procedure, and at the 8-month follow-up examination. The Breslow-Day test was used to formally assess the similarity of treatment effect between diabetic and nondiabetic patients. RESULTS: Target lesion and target vessel revascularization rates and angiographic restenosis rates in diabetic and nondiabetic patients treated with beta radiation or placebo were analyzed. Diabetic patients were more likely to have longer and more complex coronary lesions. In-hospital outcomes in diabetic and nondiabetic patients were similar, irrespective of treatment status. At 8 months, patients treated with beta radiation exhibited less target lesion revascularization (diabetic: 10.9% vs. 22.7%, p = 0.02; nondiabetic: 12.8% vs. 22.3%, p = 0.007) and less target vessel revascularization (diabetic: 14.7% vs. 25.3%, p = 0.06; nondiabetic: 16.6% vs. 23.6%, p = 0.06) compared to placebo. In-stent binary angiographic restenosis was lower in irradiated patients (diabetic: 19.4% vs. 37.3% for placebo, p = 0.01; nondiabetic: 12.9% vs. 43% for placebo, p < 0.001). However, restenosis beyond the stent site reduced the impact of VBT, regardless of diabetic status. The magnitude of the treatment effect for target lesion and target vessel revascularization rates was similar between diabetic and nondiabetic patients. CONCLUSIONS: Previously published institutional experiences have suggested that diabetic patients benefit from the use of VBT in the management of in-stent restenosis. This analysis now provides direct evidence to support the role of beta radiation VBT in this patient population. Diabetic patients undergoing this therapy are just as likely to benefit from it as their nondiabetic counterparts.

Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial.

CONTEXT: Following percutaneous coronary intervention (PCI), short-term clopidogrel therapy in addition to aspirin leads to greater protection from thrombotic complications than aspirin alone. However, the optimal duration of combination oral antiplatelet therapy is unknown. Also, although current clinical data suggest a benefit for beginning therapy with a clopidogrel loading dose prior to PCI, the practical application of this therapy has not been prospectively studied. OBJECTIVES: To evaluate the benefit of long-term (12-month) treatment with clopidogrel after PCI and to determine the benefit of initiating clopidogrel with a preprocedure loading dose, both in addition to aspirin therapy. DESIGN, SETTING, AND PARTICIPANTS: The Clopidogrel for the Reduction of Events During Observation (CREDO) trial, a randomized, double-blind, placebo-controlled trial conducted among 2116 patients who were to undergo elective PCI or were deemed at high likelihood of undergoing PCI, enrolled at 99 centers in North America from June 1999 through April 2001. INTERVENTIONS: Patients were randomly assigned to receive a 300-mg clopidogrel loading dose (n = 1053) or placebo (n = 1063) 3 to 24 hours before PCI. Thereafter, all patients received clopidogrel, 75 mg/d, through day 28. From day 29 through 12 months, patients in the loading-dose group received clopidogrel, 75 mg/d, and those in the control group received placebo. Both groups received aspirin throughout the study. MAIN OUTCOME MEASURES: One-year incidence of the composite of death, myocardial infarction (MI), or stroke in the intent-to-treat population; 28-day incidence of the composite of death, MI, or urgent target vessel revascularization in the per-protocol population. RESULTS: At 1 year, long-term clopidogrel therapy was associated with a 26.9% relative reduction in the combined risk of death, MI, or stroke (95% confidence interval [CI], 3.9%-44.4%; P =.02; absolute reduction, 3%). Clopidogrel pretreatment did not significantly reduce the combined risk of death, MI, or urgent target vessel revascularization at 28 days (reduction, 18.5%; 95% CI, -14.2% to 41.8%; P =.23). However, in a prespecified subgroup analysis, patients who received clopidogrel at least 6 hours before PCI experienced a relative risk reduction of 38.6% (95% CI, -1.6% to 62.9%; P =.051) for this end point compared with no reduction with treatment less than 6 hours before PCI. Risk of major bleeding at 1 year increased, but not significantly (8.8% with clopidogrel vs 6.7% with placebo; P =.07). CONCLUSIONS: Following PCI, long-term (1-year) clopidogrel therapy significantly reduced the risk of adverse ischemic events. A loading dose of clopidogrel given at least 3 hours before the procedure did not reduce events at 28 days, but subgroup analyses suggest that longer intervals between the loading dose and PCI may reduce events.