William H. Matthai

Argatroban anticoagulation during percutaneous coronary intervention in patients with heparin‐induced thrombocytopenia

Heparin‐induced thrombocytopenia (HIT) is an immune‐mediated syndrome associated with thrombosis. Alternative anticoagulation to heparin is needed for HIT patients during percutaneous coronary intervention (PCI). We evaluated argatroban, a direct thrombin inhibitor, for anticoagulation in this setting. Ninety‐one HIT patients underwent 112 PCIs while on intravenous argatroban (25 μg/kg/min [350 μg/kg initial bolus], adjusted to achieve an activated clotting time of 300–450 sec). Primary efficacy endpoints were subjective assessments of the satisfactory outcome of the procedure and adequate anticoagulation during PCI. Among patients undergoing initial PCIs with argatroban (n = 91), 94.5% had a satisfactory outcome of the procedure and 97.8% achieved adequate anticoagulation. Death (zero patients), myocardial infarction (four patients), or revascularization (four patients) at 24 hr after PCI occurred in seven (7.7%) patients overall. One patient (1.1%) experienced periprocedural major bleeding. For patients who had subsequent hospitalizations (mean separation of 150 days) for repeat PCI using argatroban anticoagulation (n = 21), there were no unsatisfactory outcomes. Overall, outcomes were comparable with those historically reported for heparin. Argatroban therefore is a reasonable anticoagulant option in this setting, where current options are limited. Cathet Cardiovasc Intervent 2002;57:177–184.

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.

Role of cardiac troponin T in the long-term risk stratification of patients undergoing percutaneous coronary intervention

AIMS To investigate the long-term prognostic significance of pre- and post-procedure troponin T (TnT) elevations in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS TnT and CK-MB were measured pre- and post-procedure in 212 patients undergoing PCI. Major adverse events (composite of death, myocardial infarction and revascularization) were ascertained 6 years later. Pre-procedural TnT was a significant independent predictor of time to major events (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.16-2.64) and death or myocardial infarction. Post-procedural TnT elevation above normal was the only independent predictor of the primary end-point at 1 year (HR 2.39, 95% CI 1.09-5.26) but was not significantly related to event-free survival throughout follow-up. Post-PCI elevation of TnT 5x above normal, however, did significantly predict time to events during the entirety of follow-up. By contrast, CK-MB was not an independent predictor in any of the analyses. CONCLUSIONS Our study confirms the long-term prognostic value of pre-procedural TnT elevation in patients undergoing PCI, and demonstrates the superior predictive ability of a post-procedural increase in TnT 5x normal for long-term adverse events. Whether the prognostic significance of smaller post-procedural TnT elevations extends beyond the intermediate-term awaits further investigation.

Stroke After Aortic Valve Surgery Results From a Prospective Cohort

Background— The incidence and impact of clinical stroke and silent radiographic cerebral infarction complicating open surgical aortic valve replacement (AVR) are poorly characterized. Methods and Results— We performed a prospective cohort study of subjects ≥65 years of age who were undergoing AVR for calcific aortic stenosis. Subjects were evaluated by neurologists preoperatively and postoperatively and underwent postoperative magnetic resonance imaging. Over a 4-year period, 196 subjects were enrolled at 2 sites (mean age, 75.8±6.2 years; 36% women; 6% nonwhite). Clinical strokes were detected in 17%, transient ischemic attack in 2%, and in-hospital mortality was 5%. The frequency of stroke in the Society for Thoracic Surgery database in this cohort was 7%. Most strokes were mild; the median National Institutes of Health Stroke Scale was 3 (interquartile range, 1–9). Clinical stroke was associated with increased length of stay (median, 12 versus 10 days; P=0.02). Moderate or severe stroke (National Institutes of Health Stroke Scale ≥10) occurred in 8 (4%) and was strongly associated with in-hospital mortality (38% versus 4%; P=0.005). Of the 109 stroke-free subjects with postoperative magnetic resonance imaging, silent infarct was identified in 59 (54%). Silent infarct was not associated with in-hospital mortality or increased length of stay. Conclusions— Clinical stroke after AVR was more common than reported previously, more than double for this same cohort in the Society for Thoracic Surgery database, and silent cerebral infarctions were detected in more than half of the patients undergoing AVR. Clinical stroke complicating AVR is associated with increased length of stay and mortality.Background— The incidence and impact of clinical stroke and silent radiographic cerebral infarction complicating open surgical aortic valve replacement (AVR) are poorly characterized. Methods and Results— We performed a prospective cohort study of subjects ≥65 years of age who were undergoing AVR for calcific aortic stenosis. Subjects were evaluated by neurologists preoperatively and postoperatively and underwent postoperative magnetic resonance imaging. Over a 4-year period, 196 subjects were enrolled at 2 sites (mean age, 75.8±6.2 years; 36% women; 6% nonwhite). Clinical strokes were detected in 17%, transient ischemic attack in 2%, and in-hospital mortality was 5%. The frequency of stroke in the Society for Thoracic Surgery database in this cohort was 7%. Most strokes were mild; the median National Institutes of Health Stroke Scale was 3 (interquartile range, 1–9). Clinical stroke was associated with increased length of stay (median, 12 versus 10 days; P =0.02). Moderate or severe stroke (National Institutes of Health Stroke Scale ≥10) occurred in 8 (4%) and was strongly associated with in-hospital mortality (38% versus 4%; P =0.005). Of the 109 stroke-free subjects with postoperative magnetic resonance imaging, silent infarct was identified in 59 (54%). Silent infarct was not associated with in-hospital mortality or increased length of stay. Conclusions— Clinical stroke after AVR was more common than reported previously, more than double for this same cohort in the Society for Thoracic Surgery database, and silent cerebral infarctions were detected in more than half of the patients undergoing AVR. Clinical stroke complicating AVR is associated with increased length of stay and mortality. # CLINICAL PERSPECTIVE {#article-title-47}

One-year clinical outcomes of protected and unprotected left main coronary artery stenting

Aims To evaluate outcomes for left main coronary artery (LMCA) stenting and compare results between protected (left coronary grafted) and unprotected LMCA stenting in the current bare-metal stent era. Methods We reviewed outcomes among 142 consecutive patients who underwent protected or unprotected LMCA stenting since 1997. All-cause mortality, myocardial infarction (MI), target-lesion revascularization (TLR), and the combined majoradverse clinical event (MACE) rates at one year were computed. Results Ninety-nine patients (70%) underwent protected and 43 patients (30%) underwent unprotected LMCA stenting. In the unprotected group, 86% were considered poor surgical candidates. Survival at one year was 88% for all patients, TLR 20%, and MACE 32%. At one year, survival was reduced in the unprotected group (72% vs. 95%, P <0.001) and MACE was increased in the unprotected patients (49% vs. 25%, P =0.005). Conclusions In the current era, stenting for both protected and unprotected LMCA disease is still associated with high long-term mortality and MACE rates. Stenting for unprotected LMCA disease in a high-risk population should only be considered in the absence of other revascularization options. Further studies are needed to evaluate the role of stenting for unprotected LMCA disease.

Argatroban anticoagulation in conjunction with glycoprotein IIb/IIIa inhibition in patients undergoing percutaneous coronary intervention: An open-label, nonrandomized pilot study

Background: Argatroban, a direct thrombin inhibitor, blocks clot-bound thrombin more effectively than does heparin. This multicenter, prospective pilot study evaluated the efficacy and safety of argatroban in combination with glycoprotein IIb/IIIa inhibition in patients undergoing percutaneous coronary intervention.Methods: Patients (N = 152) received argatroban as a 250- or 300-μg/kg bolus, followed by a 15-μg/kg/min infusion during percutaneous coronary intervention. An additional 150-μg/kg bolus was administered if activated clotting times 5–15 min after initiating argatroban were <275 s. Abciximab (N = 150) or double-bolus eptifibatide (N = 2) was administered simultaneously.Results: Median activated clotting times at the beginning and end of the procedure were approximately 300 s. The primary efficacy endpoint—a composite of death, myocardial infarction, or urgent revascularization at 30 days—occurred in 4 (2.6%) patients (no death, 4 myocardial infarctions, and 2 revascularizations). Two (1.3%) patients had major bleeding by the Thrombolysis in Myocardial Infarction criteria (1 retroperitoneal, 1 groin hematoma).Conclusions: Argatroban in combination with glycoprotein IIb/IIIa inhibition appears to provide adequate anticoagulation and be well tolerated with an acceptable bleeding risk for patients undergoing percutaneous coronary intervention. Additional studies are warranted.

Revascularization in severe left ventricular dysfunction: Outcome comparison of drug-eluting stent implantation versus coronary artery by-pass grafting

We compared the outcome of drug eluting stent (DES) implantation (Sirolimus or Paclitaxel) in patients with ischemic cardiomyopathy and severe left ventricular (LV) dysfunction with the outcome of a similar group of patients undergoing coronary artery by‐pass grafting (CABG).

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.

Electron-Beam Computerized Tomography Correlates with Coronary Angiogram in Chronic Kidney Disease Patients

Background/Aim: Electron-beam computerized tomography (EBCT) is able to noninvasively quantify coronary artery calcification (CAC). Chronic kidney disease (CKD) patients frequently have CAC, and clinicians are puzzled regarding the clinical significance of this finding and the diagnostic accuracy of coronary EBCT in CKD. The aim of this study was to determine the correlation in CKD patients between CAC measured by EBCT and 50% stenosis determined by coronary angiography (CA), the gold standard to identify atherosclerotic lesions. Method: We recruited 37 patients with CKD from a single institution and compared their coronary EBCT and CA results using standard statistical analysis. Results: Patients with at least one vessel with ≧50% stenosis by CA had higher mean CAC scores [2,407.9 ± (SD) 3,165.3 vs. 227 ± 443.4; p < 0.001] and higher median CAC scores (1,052 vs. 25.8; p < 0.001) as compared with those having no stenosis ≧50%. The sensitivity was 85.7%, and the specificity 82.6% using 50% stenosis as the definition for coronary artery disease and using a CAC score of 400 as a cutoff value for the EBCT results. The area under the receiver operating characteristic curve was 0.84. The diagnostic accuracy (proportion of correct results) was 83.8%. The negative predictive value was 90.5%. The receiver operating characteristic curve suggests that the optimal cutoff value for CAC scores in our cohort is 315.9, increasing the area under the receiver operating characteristic curve to 0.91. The total coronary artery stenosis was significantly associated with the CAC score (p = 0.01). Conclusions: EBCT has a very good predictive value for obstructive coronary artery disease. EBCT could be used as a screening tool in CKD patients with a low-to-intermediate risk for coronary artery disease.

Improved survival with drug-eluting stent implantation in comparison with bare metal stent in patients with severe left ventricular dysfunction

OBJECTIVE: We examined the efficacy of drug‐eluting stent (DES) implantation (Sirolimus or Paclitaxel) in patients with ischemic cardiomyopathy and severe left ventricular (LV) dysfunction and compared the outcome with a similar group of patients undergoing bare metal stent (BMS) implantation. BACKGROUND: Patients with severe LV dysfunction are a high risk group. DES may improve the long term outcomes compared with BMS. METHODS: One hundred and ninety one patients (23% women) with severe LV dysfunction (LV ejection fraction ≤35%) underwent coronary stent implantation between May 2002 and May 2005 and were available for follow‐up. One hundred and twenty eight patients received DES (Sirolimus in 72 and Paclitaxel in 54) and 63 patients had BMS. Patients with acute S‐T elevation myocardial infarction (STEMI) were excluded. The primary endpoint was cardiovascular mortality. A composite endpoint of major adverse cardiac events (MACE) including cardiovascular mortality, myocardial infarction (MI), and target vessel revascularization (TVR) was the secondary endpoint. RESULTS: Mean follow‐up was 420 ± 271 days. No differences were noted in age (69 ± 10 years vs. 70 ± 10 years, P = NS), number of vessel disease (2.3 ± 0.7 vs. 2.2 ± 0.8, P = NS), history of congestive heart failure (47% vs. 46%, P = NS), MI (60% vs. 61%, P = NS), or number of treated vessels (1.3 ± 0.5 vs. 1.3 ± 0.6, P = NS) for the DES and BMS group, respectively. Diabetes was more common among DES patients (45% vs. 25%, P = 0.01). The left ventricular ejection fraction (LVEF) was similar between the two groups (28% ± 6% vs. 26% ± 8%, P = NS for the DES and BMS, respectively). During the follow‐up, there were a total of 25 deaths of which two were cancer related (2 in DES group). There were 23 cardiac deaths, 8/126 (6%) which occurred in the DES group and 15/63 (24%) in the BMS group (P = 0.05 by log‐rank test). MACE rate was 10% for the DES group and 41% for the BMS group (P = 0.003). NYHA class improved in both groups (from 2.5 ± 0.8 to 1.7 ± 0.8 in DES and from 2 ± 0.8 to 1.4 ± 0.7 in the BMS, P = NS). CONCLUSION: Compared with bare‐metal stents, DES implantation reduces mortality and MACE in high risk patients with severe left ventricular dysfunction.