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Aims The aim of this study was to determine whether platelet reactivity on clopidogrel therapy, as measured by a point-of-care platelet function assay, is associated with thrombotic events after percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). Methods and results Platelet reactivity on clopidogrel (post-treatment reactivity) was measured with the VerifyNow P2Y12 assay (Accumetrics Inc., San Diego, CA, USA) in 380 patients undergoing PCI with sirolimus-eluting stents. Receiver-operating characteristic curve analysis was used to derive the optimal cut-off value for post-treatment reactivity in predicting 6 month out-of-hospital cardiovascular (CV) death, non-fatal MI, or stent thrombosis. The mean post-treatment reactivity was 184 ± 85 PRU (P2Y12 reaction units). The optimal cut-off for the combined endpoint was a post-treatment reactivity ≥235 PRU [area under the curve 0.711 (95% confidence interval 0.529–0.893), P = 0.03], which was similar to the threshold of the upper tertile (231 PRU). Patients with post-treatment reactivity greater than the cut-off value had significantly higher rates of CV death (2.8 vs. 0%, P = 0.04), stent thrombosis (4.6 vs. 0%, P = 0.004), and the combined endpoint (6.5 vs. 1.0%, P = 0.008). Conclusion High post-treatment platelet reactivity measured with a point-of-care platelet function assay is associated with post-discharge events after PCI with DES, including stent thrombosis. Investigation of alternative clopidogrel dosing regimens to reduce ischaemic events in high-risk patients identified by this assay is warranted.

The optimal treatment for sirolimus-eluting stent (SES) restenosis is not known. This study evaluated the safety and clinical outcome of paclitaxel-eluting stent (PES) implantation for SES restenosis. From March 2004 to July 2005, PESs were implanted in 125 patients with 140 lesions with SES restenosis. Acute and 6-month clinical outcomes were determined through review of the medical record and/or telephone interview. In-hospital major adverse cardiac events (death, nonfatal myocardial infarction, or repeat revascularization) occurred in 14 patients (11.2%), driven entirely by postprocedure non-Q-wave myocardial infarction. At a mean clinical follow-up of 7.2 +/- 1.8 months, the incidence of target lesion revascularization (TLR) was 14.0%, and the rate of major adverse cardiac events was 17.2%. Subacute thrombosis occurred in 2 patients (1.6%). Length of PES implanted, postprocedure diameter stenosis, and total occlusion of the target lesion were independent predictors of TLR. In patients with de novo SES restenosis, TLR was only 8.7%. In conclusion, at medium-term follow-up, PES implantation for SES failure appears to be safe and effective, although efficacy is decreased in the setting of total occlusions, greater residual diameter stenosis, and longer PESs.

Percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs) has a lower success rate than PCI for non-CTO lesions. We sought to determine trends in the treatment of CTOs within the current interventional era. Using 4 sequential recruitment waves of the National Heart, Lung, and Blood Institute Dynamic Registry, we assessed the relative prevalence and success rates in treating CTO (n=371) versus non-CTO (n=4,802) lesions over a 7-year period (1997 to 2004). Characteristics of attempted lesions and factors associated with PCI outcome were evaluated. CTO lesion attempts decreased by 41% over time, from 9.6% (1997 to 1998) to 5.7% (2004, p0.0001 for trend). More contemporary CTO lesions were longer (22.4 vs 17.0 mm, p=0.006 for trend), had thrombus less often (21.3% vs 35.4%, p=0.03 for trend), and were more often treated with stents (69.8% vs 45.4% p=0.02). The rate of successful intervention for CTO lesions decreased nonsignificantly during this time, from 79.7% to 71.4% (p=0.18). Using multivariable analysis, female gender (adjusted odds ratio 0.42, 95% confidence interval 0.20 to 0.88, p=0.02), and thrombus (adjusted odds ratio 0.31, 95% confidence interval 0.15 to 0.61, p=0.0008) were associated with higher success rates, whereas the presence of severe noncardiac disease (adjusted odds ratio 1.91, 95% confidence interval 1.05 to 3.45, p=0.03) was associated with a higher risk for PCI failure. Recruitment wave and patient age were not independently related to lesion success. In conclusion, during the PCI period of 1997 to 2004, CTO lesions were attempted less frequently and success rates did not increase, indicating a need for new operator techniques or device technologies to treat this important lesion subset by a percutaneous approach.

A randomized, controlled clinical trial demonstrated that intravenous (IV) fenoldopam did not prevent further deterioration in renal function after contrast administration in patients with chronic renal insufficiency. This lack of effect may have been a consequence of the inability to administer an effective renal dose of IV fenoldopam. This study sought to determine whether compared with IV administration, selective intrarenal (IR) fenoldopam would increase local concentration, leading to a higher glomerular filtration rate (GFR), and, because of first-pass renal elimination, result in lower systemic drug levels and less decrease in systemic blood pressure (BP). A randomized, controlled, open-label, partial crossover design trial was conducted in which 33 patients who underwent coronary angiography were randomized in a 1:2 ratio to control or fenoldopam (initially IV, then crossed over to IR through a bifurcated renal infusion catheter). Compared with IV fenoldopam, IR administration was associated with a significantly higher GFR (73.7 +/- 3.1 vs 62.6 +/- 2.5 ml/min, p = 0.0007) and renal plasma flow (537.2 +/- 34.0 vs 494.0 +/- 35.5 ml/min, p0.01), lower fenoldopam plasma levels (3.3 +/- 0.3 vs 4.8 +/- 0.3 ng/ml, p0.0001), and greater nadir systolic BP (125.5 +/- 3.6 vs 117.4 +/- 2.8 mm Hg, p0.0001). Two hours after drug discontinuation after contrast administration, GFRs in the patients who received IR fenoldopam remained higher than in controls (+15.0 ml/min [+25%] vs -8.0 ml/min [-14.0%], p0.05). In conclusion, this pilot trial demonstrates that the IR infusion of fenoldopam is safe and practical, producing greater renal effect and less reduction of BP than IV infusion. It would be appropriate to restudy this renal vasodilator for the prevention of contrast nephropathy, using selective IR delivery.

Objectives This study was performed to evaluate the clinical and serial angiographic outcomes of patients undergoing sirolimus-eluting stent (SES) implantation for unprotected left main coronary artery (LMCA) stenosis. Background The efficacy of SES has led to their expanded use for off-label indications, including LMCA disease. Methods Unprotected LMCA intervention with SES was attempted in 50 patients. Surveillance angiography was performed at three and nine months’ follow-up. Results The target lesion involved the distal LMCA in 47 patients (94%). In-lesion restenosis occurred in 21 patients (42%), was focal in 85% of cases, and in 82% involved the branch ostia, sparing the LMCA itself. Target lesion revascularization (TLR) occurred in 19 patients (38%) over a mean follow-up of 276 ± 57 days; TLR was ischemia-driven in 7 patients (14%). Late loss was significantly greater within the left circumflex (LCX) ostium compared to the parent vessel (PV) of the LMCA bifurcation (0.83 ± 0.89 mm vs. 0.49 ± 0.72 mm, p = 0.04). Late loss continued to increase between three- and nine-month follow-up. Final minimal luminal diameter and maximal balloon pressure were independent predictors of restenosis of the PV. Conclusions Restenosis is a frequent finding when serial angiographic follow-up is performed after SES implantation for unprotected distal LMCA lesions. Restenosis is usually focal, most often involves the LCX ostium, and often occurs without symptoms.

The purpose of this study was to evaluate the clinical outcome of patients undergoing sirolimus-eluting stent implantation for de novo lesions within saphenous vein grafts (SVGs). Although the incidence of restenosis following sirolimus-eluting stenting (SES) of native coronary arteries is low, the efficacy of SES to treat de novo lesions within SVGs has not been well studied. A total of 35 patients underwent SES implantation of 39 lesions during 36 procedures. All patients had a minimum follow-up of 6 months following the index procedure. The mean bypass graft age was 10.1 +/- 6.5 years (range, 0-23 years). In-hospital major adverse cardiac events [death, myocardial infarction, thrombosis, or target vessel revascularization (TVR)] occurred in four patients (11%). Clinical follow-up was obtained in 100% of patients (mean follow-up, 7.5 +/- 2.2 months). There was one cardiac death, presumed due to stent thrombosis. TVR occurred in only two patients (6%). Myocardial infarction (MI) occurred in four patients (11%), all attributable to a nontarget vessel. The combined endpoint of death, MI, or TVR occurred in seven patients (20%). Freedom from death, nonfatal MI, thrombosis, or any revascularization was 65%. Early experience indicates sirolimus-eluting stents for de novo saphenous vein graft lesions have a low (6%) rate of clinically driven target vessel revascularization. By 7-month follow-up, event-free survival is limited primarily by disease in nontarget vessels.

Background— Revascularization strategies often hinge on the presence and degree of left anterior descending coronary artery (LAD) stenosis. A decision for bypass surgery is often based on the durability of surgical LAD revascularization compared with percutaneous approaches. By decreasing restenosis, drug-eluting stents may have reduced the “reintervention gap” between surgery and percutaneous intervention, making the percutaneous route preferable. Methods and Results— Of the 1101 patients in the SIRIUS trial, 459 with an LAD stenosis were randomized to percutaneous intervention with either sirolimus-eluting or bare-metal stents. Baseline demographic, clinical, and angiographic data were obtained. Patients had 1-year clinical and 8-month angiographic follow-up. Baseline characteristics were similar in both groups. The majority of lesions were tubular type B lesions (69.7%) with a mean diameter of 2.73 mm and a mean length of 14.0 mm. The binary in-stent restenosis rate was 2% for the sirolimus stent group and 41.6% for the bare-metal arm (relative risk, 0.05; 95% CI, 0.02 to 0.1; P P P =NS). Conclusions— Sirolimus-eluting stents significantly decrease revascularization rates in LAD lesions. At 1 year, sirolimus-eluting stent revascularization rates are comparable to historic single vessel bypass surgery revascularization rates.

Aortic stenosis is the most common valvular lesion in patients above the age of 65. The etiology, presentation, and management of aortic stenosis differs in the elderly compared to younger patients in many ways. Many of the classic physical findings are absent in the elderly, making the diagnosis of critical aortic stenosis more difficult. Due to coexisting morbidity in many elderly patients, there is often a reluctance to recommend aortic valve replacement despite the dismal prognosis of medical therapy. In the following review, the authors discuss the pathophysiology, presentation, and management of aortic stenosis in the elderly.

We assessed the angiographic size of the common femoral artery (CFA) and the influence of demographics and comorbidites. In addition, the location of the CFA bifurcation and the site of femoral puncture were also assessed. Consecutive CFA angiograms (n = 200) were prospectively analyzed. CFA diameter was 6.9 +/- 1.4 mm and length 43.3 +/- 16.2 mm. By multivariate analysis, only diabetes (P < 0.001), female gender (P < 0.0005), and small body surface area (P < 0.01) predicted small vessel size. Vessel length correlated with patient height (P < 0.0005). CFA bifurcation occurred at or below the femoral head center in 98.5%. The femoral puncture was into a vessel other than the CFA in 13%, and 54% of punctures were in a less than ideal anatomical location. In conclusion, the CFA is a relatively small diameter vessel, particularly in diabetics and women. Puncture above the femoral head center and below the superior margin of the acetabulum accurately predicts an ideal puncture site. Thus, routine fluoroscopic guidance should be considered. Cathet Cardiovasc Intervent 2001;53:289-295.

Effects of Dofetilide in Canine Atrial Flutter. Introduction: Previous studios that Class III antiarrhythmic drugs are more effective in reentrant arrhythmias because they prolong refractoriness (ERP) and wavelength and reduce dispersion of refractoriness compared to Class IA antiarrhythmic drugs, which slow conduction velocity (CV) in addition to their effects on refractoriness. Methods and Results: To test this hypothesis, the Class III drug dofetilide and the Class IA drug quinidine were studied in the experimental canine crush-injury model of atrial flutter, utilizing right atrial multipoint programmed stimulation and activation mapping. In seven dogs dofetilide prolonged ERP by 23%, slowed CV by 9% at 200-msec cycle length (P < 0.001) and by 39% at 150-msec cycle length (P < 0.001), and increased wavelength by 11% (P < 0.02). Dofetilide reduced dispersion of ERP by 20% (P = 0.003) and adjacent electrodes with ERP difference ≥: 20 msec by 76% (P < 0.001). Dofetilide slowed atrial flutter by 37% (P = 0.003) prior to terminating and suppressing it in all dogs. In eight dogs quinidine prolonged ERP by 14% (P < 0.001), slowed CV by 14% at 200-msec cycle length (P < 0.00) and by 19% at 150-msec cycle length (P < 0.001), and reduced wavelength by 2% (P = NS). Quinidine did not reduce dispersion of refractoriness. Quinidine slowed atrial flutter by 57% (P < 0.001), terminating and suppressing it in only three dogs. Efficacy of dofetilide was greater than quinidine (P = 0.026) and correlated with reduced dispersion of ERP (r = -0.653, P = 0.01), reduced adjacent electrodes with ERP difference ≥ 20 msec (r = -0.637, P = 0.012), and prolonged wavelength (r = 0.61, P = 0.018). Dofetilide and quinidine terminated atrial flutter by similar mechanisms. Myocardial fiber orientation was nonuniform around the crush injury. Conclusions: Antiarrhythmic efficacy of dofetilide was greater than that of quinidine and correlated with drug-induced prolongation of wavelength and reduction in dispersion of refractoriness, effects produced only by dofetilide.

Adjunctive glycoprotein IIb/IIIa inhibition decreases ischemic events after percutaneous coronary intervention (PCI) but is associated with increased bleeding. We hypothesized that maximal antiplatelet therapy with aspirin, a thienopyridine, and a glycoprotein IIb/IIIa inhibitor without unfractionated heparin (UFH) would result in fewer bleeding complications and maintain efficacy in elective PCI. A total of 159 patients undergoing elective PCI were randomized to intraprocedural eptifibatide alone or eptifibatide plus UFH. Patients received aspirin 325 mg and clopidogrel 300 mg before the procedure. The primary end point was the Landefeld bleeding index. Secondary end points included the composite clinical outcome of in-hospital death, myocardial infarction, urgent target vessel revascularization, and Thrombolysis In Myocardial Infarction major bleeding, and a composite bleeding outcome of major, minor, and nuisance bleeding. The Landefeld bleeding index was significantly lower in the eptifibatide-only group compared with the eptifibatide-plus-UFH group (3.0 vs 3.9, p = 0.03). There was no significant difference in the composite clinical end point between groups (eptifibatide only 17% vs eptifibatide plus UFH 15%, p = 0.7). There was a trend toward a decrease in the composite bleeding end point in the eptifibatide-only compared with the eptifibatide-plus-UFH group (43% vs 56%, p = 0.10). In conclusion, during elective PCI, a strategy of aggressive antiplatelet therapy using aspirin, clopidogrel, and eptifibatide without anticoagulant therapy appears to decrease bleeding complications.

Recent studies in our canine crush-injury (CI) model of atrial flutter (AFL) suggest that elimination of dispersion of repolarization is an important antiarrhythmic effect of newer class 3 antiarrhythmic drugs. However, the effects of class 1a antiarrhythmic drugs on dispersion of repolarization and its relation to termination and suppression of AFL have not been studied. Therefore, the effects of quinidine 10) were studied in 8 dogs, using a 56-electrode plaque placed over the CI to map activation patterns during AFL and its induction and termination, and to measure effective refractory periods (ERP) at all 56 electrodes and conduction velocity (CV) parallel to the CI, before and after 0 (10 mg/kg over 10 min, then 3 mg/kg/hr). Results Induction of AFL at baseline was due to unidirectional block below the CI. a terminated AFL in only 3 dogs, due to conduction block below the CI, occurring either abruptly or following premature eccentric activation of the reentry circuit. Sustained AFL was reinducible after a in 5 dogs, and nonsustained AFL in 3. Mean overall ERP increased 14% from 112 ± 11 msec at baseline to 128 ± 15 msec after a (p l 0.001). ERP was longer below CI than above (115 ± 10 ms vs 109 ± 10 ms, p l 0.001). and this difference was not eliminated by a (133 ± 14 ms vs 123 ± 14 ms, p l 0.001). Overall dispersion of ERP (9.9 ± 2.3 msec) was unchanged by a (1 0.0 ± 1.3 msec, p = NS). The number of adjacent electrodes with ERP difference ≥20 msec (14.4 ± 10.4) was also not changed by a (12.5 ± 7.9, P = NS). CV was slower below the CI than above at baseline (0.7 ± 0.1 vs 0.9 ± 0.1 mis,p l 0.001), and this difference was unchanged by a (0.6 ± 0.1 vs 0.8 ± 0.1 mis,p l 0.001). although CV was slowed overall(p l 0.01). a prolonged AFL cycle length 57% from 123 ± 12 to 198 ± 37 msec (p l 0.01). Conclusion 1) Baseline dispersion of ERP and CV is important for initiating and sustaining AFL in this model. 2) The class 1a drug quinidine is relatively ineffective in terminating and suppressing AFL in this model, because it prolongs ERP less than AFL cycle length and it does not eliminate dispersion of ERP or CV