James L. Orford

Clinical outcome of patients undergoing non-cardiac surgery in the two months following coronary stenting

OBJECTIVES We sought to determine the frequency and timing of complications at our institution when surgery was performed within two months of coronary stent placement. BACKGROUND The optimal delay following coronary stent placement prior to non-cardiac surgery is unknown. METHODS We analyzed the Mayo Clinic Percutaneous Coronary Intervention and Surgical databases between 1990 and 2000 and identified 207 patients who underwent surgery in the two months following successful coronary stent placement. RESULTS Eight patients (4.0%) died or suffered a myocardial infarction or stent thrombosis. All 8 patients were among the 168 patients (4.8%, 95% confidence interval [CI] 2.1 to 9.2) undergoing surgery six weeks after stent placement; the frequency of these events ranged from 3.8% to 7.1% per week during each of the six weeks. No events occurred in the 39 patients undergoing surgery seven to nine weeks after stent placement (0%, 95% CI 0.0 to 9.0). CONCLUSIONS These data suggest that, whenever possible, non-cardiac surgery should be delayed six weeks after stent placement, by which time stents are generally endothelialized, and a course of antiplatelet therapy to prevent stent thrombosis has been completed.

Frequency and correlates of coronary stent thrombosis in the modern era: analysis of a single center registry.

OBJECTIVES The study examined the frequency, correlates, and outcome of patients with stent thrombosis within 30 days of stent placement. BACKGROUND Patients in trials evaluating stents or dual antiplatelet therapy to prevent coronary stent thrombosis have generally had narrow inclusion criteria; the extent to which stent thrombosis rates in such trials represent current practice, particularly with the availability of newer stents, is unclear. METHODS We performed a retrospective analysis of the Mayo Clinic Percutaneous Coronary Intervention database and identified all patients who received at least one coronary stent and dual antiplatelet therapy (aspirin and ticlopidine or clopidogrel for two to four weeks). RESULTS Four thousand five hundred nine patients underwent successful coronary stent implantation and were treated with dual antiplatelet therapy between July 1, 1994, and April 30, 2000. Stent thrombosis occurred in 23 patients (0.51%; 95% confidence interval 0.32%, 0.76%) within 30 days of stent placement. Multivariate analysis using bootstrap model selection to avoid over-fitting the model indicated that only the number of stents placed was an independent correlate of stent thrombosis (odds ratio 1.80, p < 0.001). The frequency of death and frequency of nonfatal myocardial infarction (MI) among the 23 patients with stent thrombosis were 48% and 39%, respectively. CONCLUSIONS Stent thrombosis is even more rare in the current era than in earlier trials. Number of stents placed was an independent correlate of stent thrombosis. Most patients who suffer stent thrombosis either die or suffer MI.

Incidence, correlates, management, and clinical outcome of coronary perforation: analysis of 16,298 procedures

BACKGROUND Coronary perforation is a serious but uncommon complication of percutaneous coronary intervention (PCI) and is associated with significant morbidity and mortality. METHODS We performed an analysis of the Mayo Clinic PCI database. Clinical records, procedural reports, and angiographic studies were reviewed. Multiple logistic regression analysis was performed to identify clinical, procedural, anatomic, and angiographic correlates of coronary perforation. RESULTS A total of 16,298 PCI procedures were performed between January 1990 and December 2001. We identified 95 coronary perforations (0.58%; 95% CI, 0.47-0.71). The incidence of coronary perforation varied with time. Correlates of coronary perforation included the use of an atheroablative device and female sex. Twelve patients (12.6%) sustained an acute myocardial infarction, and cardiac tamponade developed in 11 patients (11.6%). Management strategies included reversal of heparin, pericardiocentesis, placement of a covered stent, and surgical repair. Seven patients died (7.4%). CONCLUSIONS Coronary perforation during PCI is rare, but is associated with significant morbidity and mortality. The variable frequency of perforation may be explained by temporal variations in the use of atheroablative devices.

The comparative pathobiology of atherosclerosis and restenosis

Percutaneous coronary interventions (PCIs) play an increasingly important role in the management of patients with coronary artery disease. However, these important procedures are complicated by restenosis in a sizeable number of patients. The pathobiology of atherosclerosis comprises a complex interaction among lipids, the endothelium, circulating and tissue inflammatory cells, platelets, and vascular smooth muscle cells. The superimposition of the mechanical and cellular consequences of PCIs on the abnormal substrate of atherosclerosis leads to a characteristic and distinct pathobiology that initiates and perpetuates restenosis. A clear understanding of the significant differences between atherosclerosis and restenosis will provide a rational basis for developing treatment plans that always address both problems. This article reviews and contrasts the pathobiology of atherosclerosis and restenosis and compares the mechanisms and time-course of these distinct entities.

Distal protection devices during percutaneous coronary and carotid interventions

Distal embolization of particulate matter complicates percutaneous coronary and peripheral interventions more often than had been recognized until recently. A number of distal protection devices are under development. The PercuSurge GuardWire™ is a balloon occlusion thrombectomy device approved by the United States Food and Drug Administration for saphenous vein graft intervention. A number of filter devices utilize an expandable filter mounted on the angioplasty guidewire to facilitate entrapment of particles and safe removal. The Parodi Anti-Emboli System™ is an example of a catheter occlusion device that establishes protection by reversing blood flow in the target vessel.

Impact of intra-aortic balloon counterpulsation with different balloon volumes on cardiac performance in humans

Intra‐aortic balloon (IAB) counterpulsation can augment the cardiac output. However, the effect of different IAB volumes on cardiac performance has not been adequately evaluated in humans. Eighty‐two patients (52 males [63%]; mean age, 65 ± 12 years; mean body surface area [BSA], 1.8 ± 0.2 m2) had IAB counterpulsation for cardiogenic shock, refractory angina, and preoperatively for high‐risk cardiac surgery. Cardiac hemodynamics were prospectively studied during IAB with inflation volumes of 32 vs. 40 cc. Hemodynamic data collected included aortic pressure, pulmonary artery pressure, systemic and mixed venous oxygen saturations, and cardiac output (by Fick). Transthoracic echocardiography (TTE) was used to obtain both velocity time integrals (VTIs) and the area of the left ventricular outflow tract (LVOT). Left ventricular stroke volume was then calculated as LVOT area × VTI. Cardiac output (CO) determined by the Fick method and VTI did not differ significantly (P = NS) between the two inflation volumes (y = 0.002 + 0.97×). In a subgroup of 33 patients with BSA ≤ 1.8 m2, the CO (by VTI) was slightly lower with IAB inflation volume of 32 vs. 40 cc (P = 0.05). Overall, smaller IAB inflation volumes do not affect the hemodynamic improvement seen during IAB counterpulsation. However, in patients with smaller BSA, larger inflation volumes may further augment CO. Cathet Cardiovasc Intervent 2002;57:199–204.

Clopidogrel inhibits shear-induced platelet function.

We enrolled 17 healthy adult volunteers and measured platelet hemostasis time (PHT) and collagen-induced thrombus formation (CITF) before and after the oral administration of 300 mg of clopidogrel utilizing the Xylum Clot Signature Analyzer®. We documented a statistically significant 30% prolongation of the PHT from 291 - 13 (SE) seconds to 376 - 31 (SE) s ( P =0.037). There was a 7% prolongation of the CITF from 347 - 10 to 371 - 17 (SE) s ( P =0.245). This study suggests that the Xylum Clot Signature Analyzer can measure changes in platelet function in response to a modest platelet inhibitor, and may be a useful clinical tool for the monitoring of antiplatelet therapies in patients.

Cutting balloon angioplasty vs. conventional balloon angioplasty in patients receiving intracoronary brachytherapy for the treatment of in-stent restenosis

The objective of this study was to evaluate the safety and efficacy of cutting balloon angioplasty (CBA) for the treatment of in‐stent restenosis prior to intracoronary brachytherapy (ICB). Cutting balloon angioplasty may reduce the incidence of uncontrolled dissection requiring adjunctive stenting and may limit “melon seeding” and geographic miss in patients with in‐stent restenosis who are subsequently treated with ICB. We performed a retrospective case‐control analysis of 134 consecutive patients with in‐stent restenosis who were treated with ICB preceded by either CBA or conventional balloon angioplasty. We identified 44 patients who underwent CBA and ICB, and 90 control patients who underwent conventional percutaneous transluminal coronary angioplasty (PTCA) and ICB for the treatment of in‐stent restenosis. Adjunctive coronary stenting was performed in 13 patients (29.5%) in the CBA/ICB group and 41 patients (45.6%; P < 0.001) in the PTCA/ICB group. There was no difference in the injury length or active treatment (ICB) length. The procedural and angiographic success rates were similar in both groups. There were no statistically significant differences in the incidence of death, myocardial infarction, recurrent angina pectoris, subsequent target lumen revascularization, or the composite endpoint of all four clinical outcomes (P > 0.05). Despite sound theoretical reasons why CBA may be better than conventional balloon angioplasty for treatment of in‐stent restenosis with ICB, and despite a reduction in the need for adjunctive coronary stenting, we were unable to identify differences in clinical outcome. Catheter Cardiovasc Interv 2004;63:152–157.

Does Clopidogrel Increase the Degree of Platelet Inhibition When a Platelet Glycoprotein IIb/IIIa Inhibitor Has Been Given? Insights From an Optical Platelet Aggregometry Study

Introduction: While the CURE trial demonstrated the benefits of clopidogrel in acute coronary syndromes, patients receiving glycoprotein IIb/IIIa antagonists were excluded. Given the frequent coadministration of these two medications, we sought to examine their interaction and their combined effect on platelet inhibition.Methods: Ten patients admitted to the hospital with stable or unstable angina underwent phlebotomy prior to, three hours and six hours after administration of a standard oral loading dose of clopidogrel. The samples were then treated in vitro with incremental concentrations of tirofiban (0, 10, 20, 40, 60, and 80 ng/mL), and optical platelet aggregometry was performed utilizing ADP and TRAP as agonists. We analyzed the combined effects of these agents using a mixed effects model with time and tirofiban concentration as fixed effects, and subject and timing of phlebotomy as random effects.Results: There was no evidence of additional inhibition of platelet aggregation due to clopidogrel regardless of the concentration of tirofiban or the study agonist (ADP 20 μM or iso-TRAP). Specifically, there was no difference in the tirofiban dose-response curves with either platelet agonist for any of the three time points (before, and three and six hours after, clopidogrel administration).Discussion: There is no evidence that the combination of clopidogrel and tirofiban achieves greater inhibition of platelet aggregation than tirofiban alone.

Modulating thrombotic potential in catheter-based percutaneous coronary and peripheral vascular interventions

Thrombosis is an obligatory consequence of all percutaneous vascular interventions. Balloon angioplasty, intravascular stents and other devices routinely used to facilitate dilatation of critical vascular stenoses result in fracture of the intima and exposure of the thrombogenic subendothelium with initiation and perpetuation of platelet activation and aggregation [1,2]. This not uncommonly results in thrombus formation that may lead to abrupt vessel closure, distal ischemia and tissue infarction, and target organ dysfunction. Fortunately, advances in our understanding of the mechanisms that underlie vascular thrombosis have led to advances in the use of adjunctive pharmacological agents that modulate this pathophysiological response and have led to important reductions in the incidence and severity of thrombotic complications of percutaneous transluminal interventions.