Interventional therapies and in-hospital outcomes in acute coronary syndromes complicated by von Willebrand disease.

INTRODUCTION: von Willebrand disease (VWD) is one of the most common inherited bleeding disorders. AIM: Investigate the impact of the VWD bleeding tendency on in-hospital management of acute coronary syndromes (ACS). METHODS: Using discharge data from the National Inpatient Sample (NIS), the features of presentation and in-hospital treatment among ACS hospital discharges with and without a VWD diagnosis were investigated. A total of 264 case discharges and 705 860 control discharges were identified. RESULTS AND CONCLUSIONS: There was a significantly higher percentage of women among the case discharges compared to the control discharges (59.5% and 39.4%, respectively; P < 0.001). The rate of medical therapy alone [i.e. avoidance of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)] was significantly higher among unstable angina cases than controls (55.0% vs. 46.4%; P = 0.01), and among cases undergoing PCI, bare-metal stents (BMS) were utilized in preference to drug-eluting stents (DES) (adjusted OR = 3.5); P < 0.001). No difference in in-hospital death was identified, but reported bleeding among discharges that underwent CABG was higher in cases compared to controls (12.9% vs. 5.2%; P = 0.047). Although medical and interventional management of ACS appears to be well tolerated in the majority of hospitalized patients with VWD, the gender ratio is reversed, interventions and DES are utilized less frequently and procedure-related bleeding may be increased, calling for further study.

Randomized trial of contrast media utilization in high-risk PTCA: the COURT trial.

BACKGROUND: Previous in vitro and in vivo studies have suggested an association between thrombus-related events and type of contrast media. Low osmolar contrast agents appear to improve the safety of diagnostic and coronary artery interventional procedures. However, no data are available on PTCA outcomes with an isosmolar contrast agent. METHODS AND RESULTS: A multicenter prospective randomized double-blind trial was performed in 856 high-risk patients undergoing coronary artery intervention. The objective was to compare the isosmolar nonionic dimer iodixanol (n=405) with the low osmolar ionic agent ioxaglate (n=410). A composite variable of in-hospital major adverse clinical events (MACE) was the primary end point. A secondary objective was to evaluate major angiographic and procedural events during and after PTCA. The composite in-hospital primary end point was less frequent in those receiving iodixanol compared with those receiving ioxaglate (5.4% versus 9.5%, respectively; P=0.027). Core laboratory defined angiographic success was more frequent in patients receiving iodixanol (92.2% versus 85. 9% for ioxaglate, P=0.004). There was a trend toward lower total clinical events at 30 days in patients randomized to iodixanol (9.1% versus 13.2% for ioxaglate, P=0.07). Multivariate predictors of in-hospital MACE were use of ioxaglate (P=0.01) and treatment of a de novo lesion (P=0.03). CONCLUSIONS: In this contemporary prospective multicenter trial of PTCA in the setting of acute coronary syndromes, there was a low incidence of in-hospital clinical events for both treatment groups. The cohort receiving the nonionic dimer iodixanol experienced a 45% reduction in in-hospital MACE when compared with the cohort receiving ioxaglate.

Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an immune-mediated syndrome caused by heparin. Complications range from thrombocytopenia to thrombocytopenia with thrombosis. We report a prospective, historical- controlled study evaluating the efficacy and safety of argatroban, a direct thrombin inhibitor, as anticoagulant therapy in patients with HIT or HIT with thrombosis syndrome (HITTS). METHODS AND RESULTS: Patients with HIT (isolated thrombocytopenia, n=160) or HITTS (n=144) received 2 microgram. kg(-1). min(-1) IV argatroban, adjusted to maintain the activated partial thromboplastin time 1.5 to 3.0 times baseline value. Treatment was maintained for 6 days, on average. Clinical outcomes over 37 days were compared with those of 193 historical control subjects with HIT (n=147) or HITTS (n=46). The incidence of the primary efficacy end point, a composite of all-cause death, all-cause amputation, or new thrombosis, was reduced significantly in argatroban-treated patients versus control subjects with HIT (25.6% versus 38.8%, P=0.014). In HITTS, the composite incidence in argatroban-treated patients was 43.8% versus 56.5% in control subjects (P=0.13). Significant between-group differences by time-to-event analysis of the composite end point favored argatroban treatment in HIT (P=0.010) and HITTS (P=0.014). Argatroban therapy, relative to control subjects, also significantly reduced new thrombosis and death caused by thrombosis (P<0.05). Argatroban-treated patients achieved therapeutic activated partial thromboplastin times generally within 4 to 5 hours of starting therapy and, compared with control subjects, had a significantly more rapid rise in platelet counts (P=0.0001). Bleeding events were similar between groups. CONCLUSIONS: Argatroban anticoagulation, compared with historical control subjects, improves clinical outcomes in patients who have heparin-induced thrombocytopenia, without increasing bleeding risk.

Antithrombin activity during the period of percutaneous coronary revascularization: relation to heparin use, thrombotic complications and restenosis.

OBJECTIVES: This study evaluated changes in antithrombin (AT) activity around the time of percutaneous transluminal coronary revascularization (PTCR) with unfractionated heparin anticoagulation and the effects these changes had on major thrombotic complications of PTCR. BACKGROUND: Heparin is used during PTCR to prevent thrombosis. However, heparin, a cofactor for AT, causes AT activity to fall. AT activity <70% is associated with thrombosis. There is a prothrombotic state after heparin discontinuation that has not been well explained. METHODS: Antithrombin activity was sampled at the start and end of PTCR and the next two mornings in 250 consecutive patients. We recorded occurrence of major thrombotic events, defined as 1) major thrombotic complications of PTCR; 2) major in-lab thrombus formation; or 3) subacute occlusion. Discriminant analysis was employed to evaluate the relationship of AT activity to these events. Change in AT activity and its relationship to heparin was evaluated. Evidence of restenosis at six months was obtained. RESULTS: There were 14 major thrombotic events. Antithrombin activity <70% was strongly (p = 0.006) associated with these events. The AT activity fell significantly through the morning after PTCR when 21% of patients had AT activity <70%; AT activity did not normalize until >20 h after heparin discontinuation. Pre-PTCR use of heparin led to lower AT activity in proportion to duration of heparin use. There was no relationship between AT activity and restenosis. CONCLUSIONS: Low AT activity may contribute to major thrombotic complications of PTCR. The way heparin is used before and after PTCR is important to development of low AT activity.

Expected hemoglobin decrease following percutaneous transluminal coronary angioplasty.

To establish expected changes in hemoglobin during and after percutaneous transluminal coronary angioplasty (PTCA), we measured hemoglobin before, at the end of, and on the 2 mornings after PTCA in 177 consecutive patients without obvious out-of-laboratory blood loss. From these data, we calculated confidence intervals that can be used to compare group data, possibly to identify excessive blood loss with new devices or antithrombotic agents, and prediction intervals to identify unexpected blood loss in an individual patient.

Predictors of clinical outcome following percutaneous intervention for in-stent restenosis.

Percutaneous intervention for the first episode of in-stent restenosis was performed in 177 patients 5.4 +/- 0.3 months after native coronary stent implantation. Medical records were reviewed and patients contacted 13.3 +/- 1.2 months after in-stent intervention to ascertain the subsequent clinical course. The effects of demographic, procedural, and angiographic variables on clinical outcomes were determined. At 2 years, Kaplan-Meier estimated survival was 93 +/- 3% and freedom from death, myocardial infarction, and a third target artery revascularization (TAR) was 67 +/- 4%. The actuarial frequency of a third TAR was 26 +/- 4% at 1 year. Stratification of outcomes according to timing of in-stent intervention revealed an approximate twofold higher frequency of adverse events among patients with early (

Adverse effects of calcium binding contrast agents in diagnostic cardiac angiography. A comparison between formulations with and without calcium binding additives.

RATIONALE AND OBJECTIVES: The authors compared complications and hemodynamic and electrophysiologic effects of two formulations of diatrizoate, one with additives that bind calcium and one without, in diagnostic cardiac angiography. METHODS: Two hundred twenty-three consecutive low-risk patients alternately received Hypaque 76 (group 1, little calcium binding effect), and MD 76 (group 2, significant calcium binding). Electrocardiographic and hemodynamic changes related to coronary angiography and left ventriculography were measured, and complications requiring treatment were recorded. RESULTS: There were more complications in patients in group 2 than in group 1 (18 versus 8, P = 0.04). Arterial pressure fell more, the QT interval increased more, and the heart rate fell more in group 2 after coronary angiography. CONCLUSIONS: Formulations of diatrizoate that minimize calcium binding are advocated for cardiac angiography when using high osmolality contrast media. The more detrimental effects that calcium binding has on myocardial function and cardiac conduction may lead to the higher incidence of complications.

Clinical and economic factors in the selection of low-osmolality contrast media.

Both high- and low-osmolality contrast media are available for most radiographic procedures requiring iodinated contrast material. Newer low-osmolality contrast media cost much more than conventional high-osmolality formulations but cause fewer adverse reactions. However, most of these reactions are mild and easily treated, and do not affect the outcome of the procedure. Whether these additional clinical benefits justify the added cost is a crucial question which has not been answered. This review introduces some of the economic and clinical issues on which the choice of contrast media should be based. Low-osmolality contrast agents are not cost effective considering current pricing strategies and current inability to select patients at increased risk of an adverse event. Therefore, a better understanding of these adverse events and their mechanism takes on added importance.

Catheter-induced spasm of the left main coronary artery.

Catheter-induced spasm of the left main coronary artery is rare during catheterization. We present several cases in which the occurrence of both ostial left main and right coronary spasm suggests that multiple sites of spasm may be a clue to this important diagnosis.

A randomized controlled trial of the efficacy, safety and cost of a single-use myocardial bioptome.

A randomized single-blind study was performed comparing a reusable 8 French bioptome with a single-use 7 French bioptome in a consecutive series of 63 myocardial biopsy procedures performed during follow-up of cardiac transplant patients. Safety, efficacy and cost were compared between 30 procedures performed with the single-use bioptome (Group I) and 33 procedures performed with the reusable bioptome (Group II). The two instruments were found equally efficient in obtaining adequate biopsy samples (69% of attempts for both instruments). The average specimen weight was not significantly different (Group I 2.5+/-1.3 mg, Group II 2.7+/-1.1 mg) despite different nominal jaw sizes. There was no significant difference in the incidence of incompletely cut specimens (Group I 13%, Group II 7%) and there were no complications in either group. The cost of the two instruments was, as expected, markedly different with an estimated average per-use cost of $250.00 for the single-use bioptome and $35.89 for the reusable instrument. In this small study, a single-use 7 French myocardial bioptome was found to be an acceptable substitute for the larger, reusable instrument with no decrement in specimen size. The substantial cost differential is noteworthy, although the maintenance required by the reusable instrument can present a formidable challenge.

Combination enoxaparin and abciximab therapy during percutaneous coronary intervention: "NICE guys finish first".

Data from randomized clinical trials support the administration of both enoxaparin and platelet glycoprotein IIb/IIIa blockade to patients who present with non-ST segment evaluation acute coronary syndromes. Enoxaparin does not activate platelets, has a more predictable dose response that facilitates weight-adjusted dosing and may have enhanced antithrombotic (increased anti-Xa activity) and safety (reduced anti-IIa activity) properties when compared with unfractionated heparin. Abciximab administration during percutaneous coronary intervention reduces the incidence of ischemic adverse outcomes and may improve survival in long-term follow-up. The preliminary experience with combining abciximab and intravenous enoxaparin during percutaneous coronary intervention in the NICE-4 Trial demonstrates a low incidence of minor/major bleeding (TIMI definition) and transfusion and infrequent major cardiac events to 30 days follow-up. Future algorithms to facilitate the transition of patients from the clinical service who have received subcutaneous administration of enoxaparin to the cardiac catheterization laboratory prior to percutaneous coronary intervention are forthcoming and will provide seamless integration of "optimal" adjunctive pharmacology through the course of hospitalization for patients with non-ST elevation acute coronary syndromes.

Enoxaparin and abciximab adjunctive pharmacotherapy during percutaneous coronary intervention.

Randomized controlled trials of patients with non-ST segment elevation acute coronary syndromes have established the superiority of enoxaparin (versus unfractionated heparin) for reducing adverse ischemic outcomes. Furthermore, adjunctive abciximab therapy during percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. Since algorithms for integrating these pharmacotherapies have not been determined, patients undergoing elective PCI were enrolled into 2 distinct and separate studies conducted by the National Investigators Collaborating on Enoxaparin (NICE) study groups (NICE 1 and NICE 4 studies). Patients in NICE 1 were administered enoxaparin 1.0 mg/kg intravenously (without abciximab) and those enrolled in NICE 4 were administered a reduced dose (0.75 mg/kg) of enoxaparin in combination with standard-dose abciximab intravenously during PCI. Bleeding events and ischemic outcomes assessed in-hospital and at 30-days post-PCI were infrequent with either pharmacologic regimen. In the dose regimens studied, enoxaparin with or without abciximab appears to provide safe and effective anticoagulation during PCI. The combination of reduced-dose enoxaparin and abciximab was associated with a low incidence of adverse outcomes (bleeding or ischemic events). Additional studies may be required to establish the relative safety and efficacy of this new adjunctive pharmacologic strategy when compared with the combination of low-dose, weight-adjusted unfractionated heparin and abciximab.

Use of argatroban during percutaneous coronary interventions in patients with heparin-induced thrombocytopenia.

Percutaneous coronary revascularization (PTCR) procedures require intense anticoagulation during the procedure to reduce the risk of a thrombotic complication. This anticoagulation is almost always performed with unfractionated heparin. Heparin, however, is far from the ideal anticoagulant for use in PTCR, and its use is contraindicated in patients with known or suspected heparin-induced thrombocytopenia (HIT) or the heparin-induced thrombocytopenia and thrombosis syndrome (HITTS). The incidence of HIT/HITTS in the population undergoing PTCR may be increased due to the widespread use of heparin in cardiovascular patients. Direct thrombin inhibitors such as argatroban do not interact with the antibody that causes HIT/HITTS, and so these agents can be used to provide anticoagulation in patients with this dangerous condition. Argatroban was used in a trial of 50 patients with known or suspected HIT or HITTS who required PTCR. Adequate anticoagulation was achieved in 98% and there was procedural success in 98% with only 1 major bleeding event. These preliminary data suggest that argatroban can be used safely and effectively as an anticoagulant during PTCR in patients with known or suspected HIT or HITTS.

Choice of contrast agents for cardiac angiography: review and recommendations based on clinically important distinctions.

Low osmolal contrast agents (LOCA) are measurably superior to high osmolal contrast agents (HOCA) in a number of properties. However, LOCA are substantially more expensive than HOCA, and universal use of LOCA for cardiac angiography would strain the health care budget. Therefore, the choice to use LOCA in place of HOCA should be based on clinically important differences. Review of available published data suggests that HOCA can be used safely and effectively for cardiac angiography in patients with mild or moderately severe heart disease. When HOCA are used, those that do not bind calcium should be chosen as they cause fewer clinically important adverse reactions than those that do bind calcium. Use of LOCA may offer added safety in high risk patients, although to date, this conclusion has not been proved with clinical experience. Nonionic LOCA may be safer to use than ionic LOCA.

Failure of endocardial biopsy from the internal jugular vein due to endocardial scar: a new indication for the femoral venous approach.

Following cardiac transplantation, patients undergo serial endomyocardial biopsies to evaluate rejection, usually by the internal jugular approach. A case report and data are presented that demonstrate that this approach becomes less efficient and occasionally impossible in the third year after transplant (53% success rate per biopsy attempt) as compared to the first year after transplant (80%) probably due to the development of endocardial scar in the area sampled by the bioptome. Alternatively, one can change to the femoral venous approach which continues to have a high success rate in the third year after transplant (83%) because a different area of the interventricular septum is sampled when this approach is used.

Effect of experimental heart failure on peripheral sympathetic vasoconstriction.

To investigate whether heart failure impairs peripheral sympathetic vasoconstriction, hindlimb vascular responses to lumbar chain stimulation (0.5-20 Hz) were studied in normal dogs and in dogs with chronic heart failure produced by rapid ventricular pacing. At lumbar chain stimulation rates of 0.5-3 Hz, hindlimb vascular responses were comparable in both groups. However, at stimulation rates of 5-20 Hz, vascular responses were significantly attenuated in the dogs with heart failure. Vascular responses to norepinephrine (0.1, 1, and 10 micrograms/min) were not altered. These findings suggest that chronic heart failure results in impaired sympathetic vasoconstriction, probably because of reduced neurotransmitter release. This abnormality may interfere with the capacity of the failing circulation to compensate for a low cardiac output and thereby intensify the severity of heart failure.

Initial experience with an intracoronary flow support device providing localized drug infusion: the Scimed Dispatch catheter.

Two cases are presented illustrating the use of a new intracoronary infusion catheter providing flow support using a unique spiral coil design. Good clinical outcomes were obtained employing 4-hr inflations with localized infusion of urokinase at the site of dissection and extensive clot formation, respectively. This low-profile catheter-mounted device may provide an alternative to stent placement in cases of acute dissection complicated by thrombus formation.

Right ventricular-vascular interaction in congestive heart failure. Importance of low-frequency impedance.

BACKGROUND: Vasodilator agents are widely used in congestive heart failure. These agents may have important effects on the pulsatile aspects of right ventricular hydraulic load. METHODS AND RESULTS: Fifteen patients with severe congestive heart failure were studied during cardiac catheterization by use of high-fidelity pressure transducers and a catheter-mounted flow velocity probe. Three graded doses of nitroprusside were infused as pulmonary artery (PA) pressure and flow were continuously recorded. From Fourier transforms of signal-averaged waves, PA impedance, hydraulic power, and wave reflection indices were derived. At the highest dose of nitroprusside (66 +/- 41 micrograms/min), cardiac output was significantly improved, whereas PA mean and wedge pressure, resistance, impedance at the first harmonic, characteristic impedance, and wave reflection amplitude were all reduced. At the dose (32 +/- 20 micrograms/min) at which cardiac output first showed improvement, only PA mean pressure and first-harmonic impedance were significantly reduced. Hydraulic power cost per unit of forward flow was also lowered at this dose, despite lack of significant change in pulmonary vascular resistance. At the lowest dose of nitroprusside (11 +/- 4 micrograms/min), six patients experienced a decrease in stroke volume, whereas the other nine were either unchanged (n = 1) or showed an increase (n = 8). Multiple regression revealed that only the change in first-harmonic impedance correlated with this effect, increasing when stroke volume decreased and decreasing when stroke volume increased (P = .02). The change in first-harmonic impedance at this dose appeared to be caused by alterations in the amplitude of PA wave reflections. At higher doses, changes in mean PA pressure (but not in pulmonary vascular resistance) correlated with changes in stroke volume. CONCLUSIONS: Nitroprusside vasodilation at low doses alters PA hemodynamics in congestive heart failure primarily through changes in low-frequency impedance. In some patients, this effect is associated with decreased stroke output. At higher doses, favorable alterations in resistance, low- and high-frequency impedance, and wave reflections all contribute to increased forward flow and decreased power requirement per unit forward flow. These findings show that ventricular-vascular interaction is importantly affected by pulmonary vasodilation and that appreciation of pulsatile properties is required to understand the effects of pulmonary vasodilation on cardiac output.