Impact of Regional Systems of Care on Disparities in Care Among Female and Black Patients Presenting With ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: The American Heart Association Mission: Lifeline STEMI (ST-segment-elevation myocardial infarction) Systems Accelerator program, conducted in 16 regions across the United States to improve key care processes, resulted in more patients being treated within national guideline goals (time from first medical contact to device: <90 minutes for direct presenters to hospitals capable of performing percutaneous coronary intervention; <120 minutes for transfers). We examined whether the effort reduced reperfusion disparities in the proportions of female versus male and black versus white patients. METHODS AND RESULTS: In total, 23 809 patients (29.3% female, 82.3% white, and 10.7% black) presented with acute STEMI between July 2012 and March 2014. Change in the proportion of patients treated within guideline goals was compared between sex and race subgroups for patients presenting directly to hospitals capable of performing percutaneous coronary intervention (n=18 267) and patients requiring transfer (n=5542). The intervention was associated with an increase in the proportion of men treated within guideline goals that presented directly (58.7-62.1%, P=0.01) or were transferred (43.3-50.7%, P<0.01). An increase was also seen among white patients who presented directly (57.7-59.9%, P=0.02) or were transferred (43.9-48.8%, P<0.01). There was no change in the proportion of female or black patients treated within guideline goals, including both those presenting directly and transferred. CONCLUSION: The STEMI Systems Accelerator project was associated with an increase in the proportion of patients meeting guideline reperfusion targets for male and white patients but not for female or black patients. Efforts to organize systems of STEMI care should implement additional processes targeting barriers to timely reperfusion among female and black patients.

Coronary Angioplasty.

Percutaneous revascularization is a widely accepted procedure to treat patients with coronary artery disease. Since its first description in the 1970s, significant technological and pharmaceutical advances have occurred and subsequently reduced the complications associated with the procedure. Large, randomized controlled trials have provided additional evidence that percutaneous revascularization improves morbidity and mortality in patients with coronary artery disease. Over the last decade, devices designed to treat patients with more complex coronary artery disease have expanded the available therapeutic options and will likely contribute to a further decline in adverse events. Despite these advances, the management of patients with acute myocardial infarction, in-stent restenosis, and multivessel coronary artery disease remains challenging. The majority of evidence supports an early, aggressive approach in patients with acute ST-elevation and non-ST-elevation myocardial infarction. Ongoing clinical trials should help to further define the role of percutaneous interventions in the optimal management of patients with coronary artery disease.

Optimal deployment of third-generation stents: an intravascular ultrasound assessment.

Third-generation intracoronary stents allow deployment at higher pressures, possibly obviating the need for high-pressure postdilations and also possibly reducing restenosis. This study evaluated the ability of the Tristar Coronary Stent System to produce optimal stent deployment as measured by intravascular ultrasound (IVUS) and quantitative coronary angiography in 46 patients. Optimal stent deployment was defined as minimal luminal area > 80% of the average of the proximal and distal reference luminal areas. After initial deployment, 74.5% of stents met criteria for optimal stent deployment by IVUS, with an average stent expansion ratio of 89.6%. Ten stents (18.2%) were postdilated. Four patients (8.7%) had a major adverse cardiac event, one patient died, one patient had a myocardial infarction, and two patients had target vessel revascularization at 6 months. The Tristar stent system produces optimal deployment without the need for routine postdilation and results in optimal clinical outcomes.

Polyethylene glycol diisocyanate decreases platelet deposition after balloon injury of rabbit femoral arteries.

BACKGROUND: Platelet deposition after angioplasty remains problematic and may contribute to intimal hyperplasia and restenosis. We proposed that polyethylene glycol diisocyanate (PEG-DISO), a polymer that rapidly forms covalent linkages with amine residues on proteins, could mask thrombogenic vascular wall proteins from platelets, thereby abrogating acute platelet deposition. METHODS AND RESULTS: To test this hypothesis, we isolated the femoral arteries of 10 New Zealand White rabbits and injured them with 3 passes of a 2F Fogarty catheter which was inserted through a distal arteriotomy. Immediately after balloon injury, (111)indium-labeled autologous platelets were infused peripherally and the injured femoral arteries were randomly treated for 1 minute with a PEG-DISO solution in one artery and a control solution of the phosphate buffered saline vehicle in the contralateral artery. Following treatment, reflow was initiated. The vessels were harvested after 1 hour and radioactivity was quantified in a gamma counter. Platelet counts were standardized by weight and expressed as platelets/mg (mean +/- SEM). Platelet deposition onto arteries treated with PEG-DISO was (1.2 +/- 0.5) x 10(6) platelets/mg compared to (5.6 +/- 4.2) x 10(6) platelets/mg onto the contralateral control arteries treated with vehicle (P < 0.005). Scanning electron micrographs of the injured vessel segment confirmed qualitatively less platelet deposition on the treated segments than on the control segments. CONCLUSION: Treatment with PEG-DISO significantly inhibited platelet deposition after vascular injury. These data support the hypothesis that treatment with PEG-DISO masks surface adhesive proteins from platelet receptors in vivo and that the resulting molecular barrier significantly reduces platelet deposition onto the damaged vessel wall for at least one hour. The formation of a molecularly thin barrier to platelet deposition may thus be a novel and effective treatment to abrogate acute intravascular thrombosis and may have value in the treatment of restenosis.

Four-dimensional analysis of cyclic changes in coronary artery shape.

The objective of this study was to derive a method for quantifying the dynamic geometry of coronary arteries. Coronary artery geometry plays an important role in atherosclerosis. Coronary artery geometry also influences the performance of coronary interventions. Conversely, implantation of stents may alter coronary artery geometry. Clinical tools to define vessel shape have not been readily available. Using a Frenet-Serret curvature analysis applied to 3D reconstruction data derived from standard coronary angiograms, 21 coronary arteries were analyzed at end-diastole (ED) and end-systole (ES). Vessels were divided anatomically: type 1 consisted of vessels lying in the AV groove (left circumflex, right coronary) and type 2 consisted of vessels overlying actively contracting myocardium (left anterior descending, diagonal, obtuse marginal, right ventricular marginal, posterior descending, posterolateral). Vessel segments were analyzed by assessing the changes in curvature, torsion, and discrete flexion points (FPs), areas of systolic bending in the arterial contour. The curvature from ED to ES of type 1 vessels was unchanged (-0.02 +/- 0.03 cm(-1)), while the curvature change of type 2 vessels showed a 38% increase (0.33 +/- 0.04 cm(-1); P < 0.001). Type 1 vessels had fewer FPs per vessel than type 2 vessels (0.38 +/- 0.18 and 2.40 +/- 0.23 FP/vessel, respectively; P < 0.001). FPs were more common in distal segments and branch vessels. A method to quantify cyclic changes in coronary artery shape was applied to 3D data sets derived from standard coronary angiograms. Coronary arteries undergo a cyclic change in shape resulting in changes in overall curvature as well as formation of discrete flexion points. These changes in vessel shape are asymmetrically distributed in coronary arteries.

An iron-binding exochelin prevents restenosis due to coronary artery balloon injury in a porcine model.

Background- Vascular smooth muscle cell (VSMC) proliferation is a critical factor in the neointima formation that causes restenosis after coronary angioplasty (PTCA). Desferri-exochelin 772SM (D-EXO), a highly diffusible, lipophilic iron chelator secreted by Mycobacterium tuberculosis, inhibits proliferation of VSMCs in culture. We hypothesized that treatment with D-EXO would inhibit neointima formation in balloon-injured vessels in vivo. Methods and Results- We subjected 24 pigs to overstretch coronary artery injury with standard PTCA balloons and then administered intramural injections of either D-EXO (n=14) or vehicle (n=10) through an Infiltrator catheter. Treatments were randomized, and the investigators were blinded with regard to treatment group until data analysis was completed. One month later, we euthanized the pigs, excised the injured coronary segments, made multiple sections of each segment, and identified the site of maximal neointima formation. An injury score based on the degree of disruption of the internal or external elastic lamina or media was assigned. D-EXO reduced stenosis index (neointima area divided by the area within the internal elastic lamina), adjusted for injury score, by 47%. Neointima thickness was also reduced. Conclusions- D-EXO, injected intramurally, substantially inhibited formation of neointima in a porcine vascular injury model.

Predictors of death and reinfarction at 30 days after primary angioplasty: the GUSTO IIb and RAPPORT trials.

BACKGROUND: Thirty-day death among recipients of fibrinolytic therapy for acute myocardial infarction (MI) is tightly correlated with easily obtainable key demographic and clinical parameters such as age, blood pressure, heart rate, and infarct location. Similar data for primary angioplasty are not available. METHODS AND RESULTS: Data from 2 large, contemporary, primary angioplasty trials were formally combined and analyzed with respect to death and death/repeat MI at 30 days through the use of multivariate logistic regression models. The 1048 patients had a median age of 62 years, and 26% were women. Thirty-eight percent had an anterior infarction. The patients underwent angioplasty at a median delay from symptom onset of 3.8 hours. Death was independently predicted by increasing age (adjusted odds ratio [OR] per decade 2.32, 95% confidence interval [CI] 1.60 to 3.42), whereas a history of smoking (OR 0.29, CI 0.13 to 0.64), Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 after angioplasty (OR vs TIMI <3 0.21, CI 0.10 to 0.45) and higher systolic blood pressure (OR per 10 mm Hg 0.73, CI 0.62 to 0. 87) were associated with lower mortality rates. Death or repeat MI was independently associated with increasing age (OR per decade 1.40, CI 1.13 to 1.76) and anterior location of the index MI (OR 1.89, CI 1.12 to 3.20). TIMI grade 3 flow (OR vs TIMI <3 0.40, CI 0.23 to 0. 68) and higher systolic blood pressure (OR per 10 mm Hg 0.79, CI 0. 71 to 0.89) were associated with a lower incidence of death/repeat MI. Time to angioplasty, heart rate, extent of coronary artery disease, participation in 1 of the 2 trials, and all common coronary risk factors did not significantly predict outcome. CONCLUSIONS: Death and reinfarction after primary angioplasty are predominantly predicted by age, hemodynamic instability, and the attainment of TIMI 3 flow in the infarct artery.

3D coronary reconstruction from routine single-plane coronary angiograms: clinical validation and quantitative analysis of the right coronary artery in 100 patients.

BACKGROUND: Current coronary angiographic techniques display complex three-dimensional (3D) coronary structures in two dimensions (2D). We have developed a 3D reconstruction (3DR) algorithm using standard single-plane angiographic images that allows for 3D display of coronary structures. The purpose of this study was to validate our 3DR algorithm and quantify anatomic characteristics of the right coronary artery (RCA) in vivo. METHODS: Accuracy and reproducibility studies were performed using 3DRs of a coronary phantom and in vivo following 3DRs in 40 patients. The anatomic features of the RCA were then quantified in 100 patients. RESULTS: Comparison of length and bifurcation angles (BA) from the phantom to the 3DRs revealed good accuracy and correlation for both (r = 0.95 and 0.93 respectively), with diameter error of < 7%. In vivo, the average root mean square (RMS) error in the spatial coordinates of the vessel centerlines was 3.12 +/- 0.77 and 3.16 +/- 0.75 mm in 20 left coronary arteries (LCA) and 20 RCAs respectively. Interobserver average RMS error was 3.47 +/- 1.96 mm and intraobserver average RMS error was 3.02 +/- 1.07 and 3.44 +/- 1.57 mm for two different operators (p = NS). The average RCA length was 10.2 +/- 1.7 cm, average radius of curvature (ROC) was 52 +/- 9 degrees, and the average 3D bifurcation angle of the posterior descending artery (PDA) from the RCA was 55 +/- 22 degrees. Foreshortening (FS) of the segments of the RCA in three 'standard' projections ranged from 0-60, 0-75, and 0-82% respectively. CONCLUSIONS: Using our 3DR algorithm patient-specific anatomic characteristics can be accurately displayed and quantified, expanding the information that can be derived from routine coronary angiography.

Effect of abciximab on the pattern of reperfusion in patients with acute myocardial infarction treated with primary angioplasty. RAPPORT investigators. ReoPro And Primary PTCA Organization and Randomized Trial.

We investigated the effect of platelet fibrinogen receptor blockade on infarct size after primary angioplasty. Abciximab significantly reduced the time-to-peak creatine kinase without affecting enzymatic infarct size, suggesting a beneficial effect on the pattern and speed of reperfusion.

Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators.

BACKGROUND: The benefit of catheter-based reperfusion for acute myocardial infarction (MI) is limited by a 5% to 15% incidence of in-hospital major ischemic events, usually caused by infarct artery reocclusion, and a 20% to 40% need for repeat percutaneous or surgical revascularization. Platelets play a key role in the process of early infarct artery reocclusion, but inhibition of aggregation via the glycoprotein IIb/IIIa receptor has not been prospectively evaluated in the setting of acute MI. METHODS AND RESULTS: Patients with acute MI of <12 hours' duration were randomized, on a double-blind basis, to placebo or abciximab if they were deemed candidates for primary PTCA. The primary efficacy end point was death, reinfarction, or any (urgent or elective) target vessel revascularization (TVR) at 6 months by intention-to-treat (ITT) analysis. Other key prespecified end points were early (7 and 30 days) death, reinfarction, or urgent TVR. The baseline clinical and angiographic variables of the 483 (242 placebo and 241 abciximab) patients were balanced. There was no difference in the incidence of the primary 6-month end point (ITT analysis) in the 2 groups (28.1% and 28.2%, P=0.97, of the placebo and abciximab patients, respectively). However, abciximab significantly reduced the incidence of death, reinfarction, or urgent TVR at all time points assessed (9.9% versus 3.3%, P=0.003, at 7 days; 11.2% versus 5.8%, P=0.03, at 30 days; and 17.8% versus 11.6%, P=0.05, at 6 months). Analysis by actual treatment with PTCA and study drug demonstrated a considerable effect of abciximab with respect to death or reinfarction: 4.7% versus 1.4%, P=0.047, at 7 days; 5.8% versus 3.2%, P=0.20, at 30 days; and 12.0% versus 6.9%, P=0.07, at 6 months. The need for unplanned, "bail-out" stenting was reduced by 42% in the abciximab group (20.4% versus 11.9%, P=0.008). Major bleeding occurred significantly more frequently in the abciximab group (16.6% versus 9.5%, P=0.02), mostly at the arterial access site. There was no intracranial hemorrhage in either group. CONCLUSIONS: Aggressive platelet inhibition with abciximab during primary PTCA for acute MI yielded a substantial reduction in the acute (30-day) phase for death, reinfarction, and urgent target vessel revascularization. However, the bleeding rates were excessive, and the 6-month primary end point, which included elective revascularization, was not favorably affected.

Effect of direct thrombin inhibition with Bivalirudin (Hirulog) on restenosis after coronary angioplasty.

The direct antithrombin, bivalirudin, did not reduce angiographic restenosis measured either as the dichotomous restenosis rate of 62% for bivalirudin and 58% for heparin (p = 0.70), or as the late loss in lumen diameter of 0.44 +/- 0.47 mm for bivalirudin and 0.39 +/- 0.53 mm for heparin (p = 0.62). Direct thrombin inhibition with bivalirudin neither reduces angiographic restenosis nor alters the impact of several established risk factors for restenosis.

Feasibility of combined percutaneous transluminal angioplasty and minimally invasive direct coronary artery bypass in patients with multivessel coronary artery disease.

BACKGROUND: Angioplasty has become an accepted treatment of patients with coronary artery disease and is now commonly used to treat patients with multivessel disease. The major disadvantage of angioplasty has been restenosis requiring repeat interventions with resultant loss of initial cost savings. Compared with the right and the circumflex coronary arteries, the left anterior descending artery (LAD) has been more adversely affected by restenosis. Recently, minimally invasive direct coronary artery bypass (MIDCAB) to the LAD through a small left anterior thoracotomy using the left internal mammary artery has been performed in some centers with excellent early results and with reduced costs compared with standard bypass surgery. METHODS AND RESULTS: We retrospectively reviewed the first 31 consecutive patients treated in our institution with integrated coronary revascularization (ICR): MIDCAB to the LAD combined with PTCA of the other diseased vessels in patients with multivessel disease. Postoperative angiography in 84% of patients revealed a patent anastomosis and normal flow in the graft and bypassed vessel. Thirty-eight (97%) of 39 vessels were successfully treated percutaneously. At a mean follow-up of 7 months, all patients are currently asymptomatic. There have been 2 adverse clinical events, both related to angioplasty and not to MIDCAB. The average length of stay at the hospital after MIDCAB was 2.79+/-1.05 days. CONCLUSIONS: These preliminary results with ICR are encouraging and suggest that a randomized, prospective clinical trial comparing ICR with standard coronary artery bypass surgery for the revascularization of symptomatic patients with multivessel disease involving the LAD is warranted.

The lack of effect of beta-carotene on restenosis in cholesterol-fed rabbits.

The success of percutaneous transluminal coronary angioplasty is limited by restenosis in 30-50% of cases. Cellular production of reactive oxygen species at the site of injury has been implicated as a contributing factor in the process of restenosis. beta-Carotene is a lipid-soluble antioxidant whose effects on this process have not been previously investigated. We attempted to elucidate whether beta-carotene treatment was capable of reducing restenosis. Femoral artery stenoses were produced by nitrogen-desiccation in rabbits fed a high-cholesterol diet. The animals were randomized to receive either a parenteral bolus of beta-carotene immediately prior to angioplasty, followed by 5 days of subcutaneous treatment (Acute Treatment); 5 days of subcutaneous pretreatment with beta-carotene followed by a parenteral bolus immediately prior to angioplasty and then another 5 days of subcutaneous treatment (Pretreatment); or vehicle only (Control). Angiography was performed immediately before and after angioplasty, and 28 days after angioplasty. The animals were then sacrificed, and the femoral arteries were harvested for histopathology. By quantitative angiography, the late loss of luminal diameter between angioplasty and final angiography was not significantly different between the acute treatment group, the pretreatment group and the control group. By histopathology, the area of intimal hyperplasia and the percent cross-sectional area stenosis were also not significantly different. The late loss in luminal diameter after angioplasty correlated significantly with the acute gain in luminal diameter produced by angioplasty. The amount of intimal hyperplasia correlated significantly with the arterial injury score assessed by histopathology. In summary, in this animal model of restenosis, parenteral beta-carotene failed to significantly reduce the amount of either intimal hyperplasia or late loss in luminal diameter after angioplasty.

Compensatory mutations in receptor function: a reevaluation of the role of methylation in bacterial chemotaxis.

During bacterial chemotaxis membrane receptor proteins are methylated and demethylated at glutamate residues. The generally accepted view is that these reactions play an essential role in the chemosensing mechanism. Strains may be isolated, however, that exhibit chemotaxis in the complete absence of methylation. These are readily obtained by selecting for chemotactic variants of a mutant that completely lacks the methylating enzyme. Methyltransferase activity is not restored; instead, the sensory-motor apparatus is genetically restructured to compensate for the methylation defect. Genetic and biochemical analyses show that the compensatory mutational locus is the structural gene for the demethylating enzyme. Thus, although mutants lacking either the methylating or demethylating enzymes are nonchemotactic, strains defective in both activities exhibit almost-wild-type chemotactic ability.