William B. Hillegass

Adoption of Radial Access and Comparison of Outcomes to Femoral Access in Percutaneous Coronary Intervention An Updated Report from the National Cardiovascular Data Registry (2007–2012)

Background— Radial access for percutaneous coronary intervention (r-PCI) is associated with reduced vascular complications; however, previous reports have shown that <2% of percutaneous coronary intervention (PCI) procedures in the United States are performed via the radial approach. Our aims were to evaluate temporal trends in r-PCI and compare procedural outcomes between r-PCI and transfemoral PCI. Methods and Results— We conducted a retrospective cohort study from the CathPCI registry (n=2 820 874 procedures from 1381 sites) between January 2007 and September 2012. Multivariable logistic regression models were used to evaluate the adjusted association between r-PCI and bleeding, vascular complications, and procedural success, using transfemoral PCI as the reference. Outcomes in high-risk subgroups such as age ≥75 years, women, and patients with acute coronary syndrome were also examined. The proportion of r-PCI procedures increased from 1.2% in quarter 1 2007 to 16.1% in quarter 3 2012 and accounted for 6.3% of total procedures from 2007 to 2012 (n=178 643). After multivariable adjustment, r-PCI use in the studied cohort of patients was associated with lower risk of bleeding (adjusted odds ratio, 0.51; 95% confidence interval, 0.49–0.54) and lower risk of vascular complications (adjusted odds ratio, 0.39; 95% confidence interval, 0.31–0.50) in comparison with transfemoral PCI. The reduction in bleeding and vascular complications was consistent across important subgroups of age, sex, and clinical presentation. Conclusions— There has been increasing adoption of r-PCI in the United States. Transradial PCI now accounts for 1 of 6 PCIs performed in contemporary clinical practice. In comparison with traditional femoral access, transradial PCI is associated with lower vascular and bleeding complication rates. # Clinical Perspective {#article-title-25}Background— Radial access for percutaneous coronary intervention (r-PCI) is associated with reduced vascular complications; however, previous reports have shown that <2% of percutaneous coronary intervention (PCI) procedures in the United States are performed via the radial approach. Our aims were to evaluate temporal trends in r-PCI and compare procedural outcomes between r-PCI and transfemoral PCI. Methods and Results— We conducted a retrospective cohort study from the CathPCI registry (n=2 820 874 procedures from 1381 sites) between January 2007 and September 2012. Multivariable logistic regression models were used to evaluate the adjusted association between r-PCI and bleeding, vascular complications, and procedural success, using transfemoral PCI as the reference. Outcomes in high-risk subgroups such as age ≥75 years, women, and patients with acute coronary syndrome were also examined. The proportion of r-PCI procedures increased from 1.2% in quarter 1 2007 to 16.1% in quarter 3 2012 and accounted for 6.3% of total procedures from 2007 to 2012 (n=178 643). After multivariable adjustment, r-PCI use in the studied cohort of patients was associated with lower risk of bleeding (adjusted odds ratio, 0.51; 95% confidence interval, 0.49–0.54) and lower risk of vascular complications (adjusted odds ratio, 0.39; 95% confidence interval, 0.31–0.50) in comparison with transfemoral PCI. The reduction in bleeding and vascular complications was consistent across important subgroups of age, sex, and clinical presentation. Conclusions— There has been increasing adoption of r-PCI in the United States. Transradial PCI now accounts for 1 of 6 PCIs performed in contemporary clinical practice. In comparison with traditional femoral access, transradial PCI is associated with lower vascular and bleeding complication rates.

Relationship Between Heparin Anticoagulation and Clinical Outcomes in Coronary Stent Intervention Observations From the ESPRIT Trial

OBJECTIVES We evaluated the relationship between the degree of heparin anticoagulation and clinical efficacy and bleeding in patients undergoing contemporary percutaneous coronary intervention (PCI) with stent implantation. BACKGROUND Despite universal acceptance of heparin anticoagulation as a standard of care in PCI, considerable controversy still exists regarding the appropriate dosing of heparin. METHODS The study population (n = 2,064) comprised all patients enrolled in the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial. The index activated clotting time (ACT) was defined as the ACT measured after the last heparin dose and before first device activation and was correlated with outcome and bleeding events. RESULTS No association was observed between decreasing ACT levels and the rate of ischemic events in the treatment or placebo arms. The incidence of the primary composite end point (death, myocardial infarction, urgent target vessel revascularization, and thrombotic bailout glycoprotein IIb/IIIa inhibitor therapy at 48 h) was actually lowest in the lowest ACT tertile for both the placebo (10.0%) and treatment groups (6.1%). When analyzed by tertile, major bleeding rates did not increase in the lowest ACT tertile in patients given placebo (0.6%) versus those receiving eptifibatide (0.7%). Major bleeding rates increased as the ACT increased in the eptifibatide-treated patients. CONCLUSIONS Ischemic end points in patients undergoing contemporary PCI with stent placement do not increase by decreasing ACT levels, at least to a level of 200 s. Bleeding events do increase with increasing ACT levels and are enhanced with eptifibatide treatment. An ACT of 200 to 250 s is reasonable in terms of efficacy and safety with the use of contemporary technology and pharmacotherapy.

Effects on platelet aggregation and fibrinolytic activity during upright posture and exercise in healthy men.

The circadian variation of acute myocardial infarction suggests that daily activities such as assuming the upright posture and performing different daily activities may trigger the onset of coronary thrombosis. Such triggering may result from unfavorable alterations in the balance between the prothrombotic and antithrombotic properties of the blood. The present study compares the effects of 2 common daily activities, assuming the upright posture and exercise, on platelet aggregation and fibrinolytic activity. In healthy male subjects, assuming the upright posture in the morning significantly increased platelet aggregation and produced only a moderate increase in fibrinolytic activity within 10 minutes. These changes were still present after 90 minutes in the upright posture. Supine posture for 45 minutes resulted in levels of fibrinolytic activity and platelet aggregation comparable to that observed before initially assuming the upright posture in the morning. Return to the supine posture for 45 minutes resulted in levels of fibrinolytic activity and platelet aggregation comparable to that observed before the initial assumption of upright posture. The changes recurred when upright posture was taken later in the day. Exercise did not increase platelet aggregation to levels beyond that produced by the upright posture, but was associated with a marked increase in fibrinolytic activity. Thus, exercise and upright posture produce distinctive alterations in the thrombogenic potential of the blood that may influence the timing of clinical vascular events.

The Learning Curve for Transradial Percutaneous Coronary Intervention Among Operators in the United States A Study From the National Cardiovascular Data Registry

Background— Adoption of transradial percutaneous coronary intervention (TRI) in the United States is low and may be related to challenges learning the technique. We examined the relationships between operator TRI volume and procedural metrics and outcomes. Methods and Results— We used CathPCI Registry data from July 2009 to December 2012 to identify new radial operators, defined by an exclusively femoral percutaneous coronary intervention approach for 6 months after their first percutaneous coronary intervention in the database and ≥15 total TRIs thereafter. Primary outcomes of fluoroscopy time, contrast volume, and procedure success were chosen as markers of technical proficiency. Secondary outcomes included in-hospital mortality, bleeding, and vascular complications. Adjusted outcomes were analyzed by using operator TRI experience as a continuous variable with generalized linear mixed models. Among 54 561 TRI procedures performed at 704 sites, 942 operators performed 1 to 10 procedures, 942 operators performed 11 to 50 procedures, 375 operators performed 51 to 100 procedures, and 148 operators performed 101 to 200 procedures. As radial caseload increased, more TRIs were performed in women, in patients presenting with ST-segment elevation myocardial infarction, and for emergency indications. Decreased fluoroscopy time and contrast use were nonlinearly associated with greater operator TRI experience, with faster reductions observed for newer (<30–50 cases) compared with more experienced (>30–50 cases) operators. Procedure success was high, whereas mortality, bleeding, and vascular complications remained low across TRI volumes. Conclusions— As operator TRI volume increases, higher-risk patients are chosen for TRI. Despite this, operator proficiency improves with greater TRI experience, and safety is maintained. The threshold to overcome the learning curve appears to be approximately 30 to 50 cases.

Safe use of platelet GP IIb/IIIa inhibitors

The platelet membrane glycoprotein IIb/IIIa receptor inhibitor abciximab is used for the treatment of patients undergoing high-risk percutaneous coronary interventions and is used in approximately one third of coronary interventions in the United States and a growing number of procedures in Europe. Recent clinical trials have shown that this potent antiplatelet agent significantly reduces the incidence of death and nonfatal myocardial infarction and the need for revascularization. With expanding experience since the commercial release of abciximab in February 1995, several strategies to enhance the safety of abciximab have emerged. In particular, new data confirm that the risk of bleeding-identified as a concern in the original EPIC trial-can be substantially reduced through the use of low-dose adjunctive heparin, early sheath removal, and fastidious postprocedure vascular access site care. Other recommendations for enhancing the safety of potent antiplatelet agents in a variety of clinical situations are provided. The following article reflects insights regarding the safety of glycoprotein IIb/IIIa inhibitors expressed by a group of international experts convened in Davos, Switzerland, February 16, 1997 This report attempts to review clinical progress to date, formulate recommendations, and map out potentially fruitful lines of inquiry for future investigation.

The association between inflammatory markers, serum lipids and the risk of cardiovascular events in patients with rheumatoid arthritis.

Objective To examine the association of serum inflammatory markers (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) and serum lipid measures (low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol) with risk of myocardial infarction (MI) and ischaemic stroke (IS) among rheumatoid arthritis (RA) patients. Methods We conducted a retrospective cohort study using 2005–2010 data from a US commercial health plan. Eligible patients had two or more physician diagnoses of RA during a baseline period of at least 180 days with continuous medical and pharmacy coverage. We computed age-adjusted incidence rates of MI and IS, and used spline regression to assess non-linear associations and Cox-regression to quantify the independent association between the laboratory values and the outcomes. Results We identified 44 418 eligible RA patients (mean age 49 years; 76% women). CRP>10 mg/L compared with <1 mg/L was associated with increased MI risk (HR 2.12; 95% CI 1.02 to 4.38). ESR>42 mm/h compared with <14 mm/h was associated with increased risk of MI (HR 2.53; 95% CI 1.48 to 4.31) and IS (HR 2.51; 95% CI 1.33 to 4.75) risk. HDL-cholesterol ≥60 mg/dL (1.6 mmol/L) compared with <40 mg/dL (1.0 mmol/L) was associated with reduced MI risk (HR 0.37; 0.21 to 0.66). The association between LDL and MI was not linear; the lowest risk was observed among patients with LDL between 70 mg/L (1.8 mmol/L) and 100 mg/L (2.6 mmol/L). We did not observe a significant association between LDL and IS. Conclusions This study provides evidence supporting the hypothesis that RA-related systemic inflammation plays a role in determining cardiovascular risk and a complex relationship between LDL and cardiovascular risk.

Overview, Strengths, and Limitations of Systematic Reviews and Meta-Analyses

While the main focus of this chapter will be meta-analysis, it cannot be completely isolated from several prerequisites assessed in the systematic review. For example, the studies must address a common question. The eligibility criteria of the underlying studies must be well established. Evaluation techniques for endpoints must be reasonably consistent across the studies. In the clinical setting, when making comparisons between a treatment and control, the underlying studies must be properly randomized. Exploratory meta-analyses and meta-regressions may examine associations between interventions, covariates, and secondary events.

Characteristics and long-term outcomes of percutaneous revascularization of unprotected left main coronary artery stenosis in the United States: a report from the National Cardiovascular Data Registry, 2004 to 2008.

OBJECTIVES This study sought to assess percutaneous coronary intervention (PCI) for unprotected left main coronary artery (ULMCA) stenosis in routine U.S. clinical practice. BACKGROUND Percutaneous coronary intervention for ULMCA stenosis is controversial; however, current use and outcomes of ULMCA PCI in routine U.S. clinical practice have not been described. METHODS We evaluated 5,627 patients undergoing ULMCA PCI at 693 centers within the National Cardiovascular Data Registry Catheterization Percutaneous Coronary Intervention Registry for temporal trends in PCI use (2004 to 2008), patient characteristics, and in-hospital mortality. Thirty-month mortality and composite major adverse events (death, myocardial infarction, and revascularization) with drug-eluting versus bare-metal stents were compared using inverse probability weighted (IPW) hazard ratios (HRs) in a nonrandomized Medicare-linked (age ≥65 years) patient cohort (n = 2,765). RESULTS ULMCA PCI was performed in 4.3% of patients with ULMCA stenosis. Unadjusted in-hospital mortality rates ranged from 2.9% for elective cases to 45.1% for emergent/salvage cases. By 30 months, 57.9% of the elderly ULMCA PCI population experienced death, myocardial infarction, or revascularization, and 42.7% died. Patients receiving drug-eluting stents (versus bare-metal stents) had a lower 30-month mortality (IPW HR: 0.84, 95% confidence interval [CI]: 0.73 to 0.96), but the composite of major adverse events were similar (IPW HR: 0.95, 95% CI: 0.84 to 1.06). CONCLUSIONS In the United States, ULMCA PCI is performed in <5% of patients with ULMCA disease and is generally reserved for those at high procedural risk. Adverse events are common in elderly patients and are related to patient and procedural characteristics, including stent type.

The effect of obesity on quality of life in patients with diabetes and coronary artery disease

BACKGROUND Obesity increases the risk of type 2 diabetes and coronary artery disease (CAD). Because all 3 conditions may reduce quality of life, the extent to which obesity, diabetes, and CAD independently affect quality of life is uncertain. METHODS Patients with type 2 diabetes and documented CAD participating in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial at 45 clinical sites in the United States and Canada were studied in a cross-sectional analysis of baseline data. Quality of life was assessed with the Duke Activity Status Index, the energy/fatigue and health distress scales from the Medical Outcome Study, and overall self-rated health status. RESULTS Higher body mass index was significantly associated with worse scores on all 4 quality of life scales, even after adjustment for the severity of diabetes and CAD and other comorbid conditions. Use of insulin, angina, and current smoking were also associated with significantly lower quality of life on all 4 scales, independent of other factors. CONCLUSIONS Obesity is associated with significantly reduced quality of life in patients with diabetes and CAD, independent of comorbid conditions.

Clinical significance of post-procedural TIMI flow in patients with cardiogenic shock undergoing primary percutaneous coronary intervention.

OBJECTIVES We sought to evaluate the impact of post-primary percutaneous coronary intervention (PCI) Thrombolysis In Myocardial Infarction (TIMI) flow grades in the infarct-related artery (IRA) in patients with ST-segment elevation myocardial infarction (STEMI) and cardiogenic shock. BACKGROUND The clinical implications and correlates of post-procedural TIMI flow grades in patients with STEMI and cardiogenic shock treated with primary PCI have not been elucidated. METHODS We evaluated 4,731 STEMI patients with cardiogenic shock undergoing primary PCI at 567 hospitals participating in the American College of Cardiology-National Cardiovascular Database CathPCI Registry to determine the association of post-procedural TIMI flow grades 0 to 2 with in-hospital outcomes. RESULTS Post-PCI TIMI flow grades 0 to 2 in the IRA were present in 14.7% of patients. Compared with patients with TIMI flow grade 3, those with TIMI flow grades 0 to 2 were more likely to undergo coronary artery bypass graft surgery after PCI (20% vs. 5.4%), and develop renal failure (10.1% vs. 5.1%), cardiac tamponade (1.0% vs. 0.5%), and bleeding requiring blood transfusion (35.2% vs. 21.6%). Unadjusted mortality was more than 2-fold higher with TIMI flow grades 0 to 2 versus TIMI flow grade 3 (63% vs. 27%). There was a graded inverse relationship with TIMI flow in the IRA and the adjusted mortality (odds ratio [OR] for TIMI flow grades 0/1: 5.47 [95% confidence interval (CI): 4.13 to 7.24] and for TIMI flow grade 2: 2.63 [95% CI: 2.02 to 3.42] compared with TIMI flow grade 3). Our study also identified factors associated with post-PCI TIMI flow grades 0 to 2. CONCLUSIONS Lack of procedural success (post-PCI TIMI flow grades 0 to 2 in the IRA) after primary PCI for STEMI among patients with cardiogenic shock is associated with a much higher risk of mortality compared with the risk for patients with normal post-PCI TIMI flow grade 3.