Kendrick A. Shunk

Detection of Lipid-Core Plaques by Intracoronary Near-Infrared Spectroscopy Identifies High Risk of Periprocedural Myocardial Infarction

Background— Percutaneous coronary intervention (PCI) is associated with periprocedural myocardial infarction (MI) in 3% to 15% of cases (depending on the definition used). In many cases, these MIs result from distal embolization of lipid-core plaque (LCP) constituents. Prospective identification of LCP with catheter-based near-infrared spectroscopy (NIRS) may predict an increased risk of periprocedural MI and facilitate development of preventive measures. Methods and Results— The present study analyzed the relationship between the presence of a large LCP (detected by NIRS) and periprocedural MI. Patients with stable preprocedural cardiac biomarkers undergoing stenting were identified from the COLOR Registry, an ongoing prospective observational study of patients undergoing NIRS before PCI. The extent of LCP in the treatment zone was calculated as the maximal lipid-core burden index (LCBI) measured by NIRS for each of the 4-mm longitudinal segments in the treatment zone. A periprocedural MI was defined as new cardiac biomarker elevation above 3× upper limit of normal. A total of 62 patients undergoing stenting met eligibility criteria. A large LCP (defined as a maxLCBI4 mm ≥500) was present in 14 of 62 lesions (22.6%), and periprocedural MI was documented in 9 of 62 (14.5%) of cases. Periprocedural MI occurred in 7 of 14 patients (50%) with a maxLCBI4 mm ≥500, compared with 2 of 48 patients (4.2%) patients with a lower maxLCBI4 mm (P=0.0002). Conclusions— NIRS provides rapid, automated detection of extensive LCPs that are associated with a high risk of periprocedural MI, presumably due to embolization of plaque contents during coronary intervention.

Detection by Near-Infrared Spectroscopy of Large Lipid Core Plaques at Culprit Sites in Patients With Acute ST-Segment Elevation Myocardial Infarction

OBJECTIVES This study sought to describe near-infrared spectroscopy (NIRS) findings of culprit lesions in ST-segment elevation myocardial infarction (STEMI). BACKGROUND Although autopsy studies demonstrate that most STEMI are caused by rupture of pre-existing lipid core plaque (LCP), it has not been possible to identify LCP in vivo. A novel intracoronary NIRS catheter has made it possible to detect LCP in patients. METHODS We performed NIRS within the culprit vessels of 20 patients with acute STEMI and compared the STEMI culprit findings to findings in nonculprit segments of the artery and to findings in autopsy control segments. Culprit and control segments were analyzed for the maximum lipid core burden index in a 4-mm length of artery (maxLCBI(4mm)). RESULTS MaxLCBI(4mm) was 5.8-fold higher in STEMI culprit segments than in 87 nonculprit segments of the STEMI culprit vessel (median [interquartile range (IQR)]: 523 [445 to 821] vs. 90 [6 to 265]; p < 0.001) and 87-fold higher than in 279 coronary autopsy segments free of large LCP by histology (median [IQR]: 523 [445 to 821] vs. 6 [0 to 88]; p < 0.001).Within the STEMI culprit artery, NIRS accurately distinguished culprit from nonculprit segments (receiver-operating characteristic analysis area under the curve = 0.90). A threshold of maxLCBI(4mm) >400 distinguished STEMI culprit segments from specimens free of large LCP by histology (sensitivity: 85%, specificity: 98%). CONCLUSIONS The present study has demonstrated in vivo that a maxLCBI(4mm) >400, as detected by NIRS, is a signature of plaques causing STEMI.

Clinical Presentation, Management, and Outcomes of Angiographically Documented Early, Late, and Very Late Stent Thrombosis

OBJECTIVES The aim of this study was to describe differences in treatment and in-hospital mortality of early, late, and very late stent thrombosis (ST). BACKGROUND Early, late, and very late ST may differ in clinical presentation, management, and in-hospital outcomes. METHODS We analyzed definite (angiographically documented) ST cases identified from February 2009 to June 2010 in the CathPCI Registry. We stratified events by timing of presentation: early (≤1 month), late (1 to 12 months), or very late (≥12 months) following stent implantation. Multivariable logistic regression modeling was performed to compare in-hospital mortality for each type of ST after adjusting for baseline comorbidities. RESULTS During the study period, 7,315 ST events were identified in 7,079 of 401,662 patients (1.8%) presenting with acute coronary syndromes. This ST cohort consisted of 1,391 patients with early ST (19.6%), 1,370 with late ST (19.4%), and 4,318 with very late ST (61.0%). Subjects with early ST had a higher prevalence of black race and diabetes, whereas subjects with very late ST had a higher prevalence of white race and a lower prevalence of prior myocardial infarction or diabetes. In-hospital mortality was significantly higher in early ST (7.9%) compared with late (3.8%) and very late ST (3.6%, p<0.001). This lower mortality for late and very late ST persisted after multivariable adjustment (odds ratio: 0.53 [95% confidence interval (CI): 0.36 to 0.79] and 0.58 [95% CI: 0.43 to 0.79], respectively). CONCLUSIONS Significant differences exist in the presentation and outcomes of early, late, and very late ST. Among patients with acute coronary syndromes who are undergoing percutaneous coronary intervention for angiographically documented ST, early ST is associated with the highest in-hospital mortality.

Predictors and outcomes of a perioperative myocardial infarction following elective vascular surgery in patients with documented coronary artery disease: results of the CARP trial.

AIMS The predictors and outcomes of patients with a peri-operative elevation in cardiac troponin I above the 99th percentile of normal following an elective vascular operation have not been studied in a homogeneous cohort with documented coronary artery disease. METHODS AND RESULTS The Coronary Artery Revascularization Prophylaxis (CARP) trial was a randomized trial that tested the benefit of coronary artery revascularization prior to vascular surgery. Among 377 randomized patients, core lab samples for peak cardiac troponin I concentrations were monitored following the vascular operation and the blinded results were correlated with outcomes. A peri-operative myocardial infarction (MI), defined by an increase in cardiac troponin I greater than the 99th percentile reference (> or =0.1 microg/L), occurred in 100 patients (26.5%) and the incidence was not dissimilar in patients with and without pre-operative coronary revascularization (24.2 vs. 28.6%; P = 0.32). By logistic regression analysis, predictors of MI (odds risk; 95%CI; P-value) were age >70 (1.84; 1.14-2.98; P = 0.01), abdominal aortic surgery (1.82; 1.09-3.03; P = 0.02), diabetes (1.86; 1.11-3.11; P = 0.02), angina (1.67; 1.03-2.64; P = 0.04), and baseline STT abnormalities (1.62; 1.00-2.6; P = 0.05). At 2.5 years post-surgery, the probability of survival in patients with and without the MI was 0.73 and 0.84, respectively (P = 0.03, log-rank test). Using a Cox proportional hazards regression analysis, a peri-operative MI in diabetic patients was a strong predictor of long-term mortality (hazards ratio: 2.43; 95% CI: 1.31-4.48; P < 0.01). CONCLUSION Among patients with coronary artery disease who undergo vascular surgery, a peri-operative elevation in cardiac troponin levels is common and in combination with diabetes, is a strong predictor of long-term mortality. These data support the utility of cardiac troponins as a means of stratifying high-risk patients following vascular operations.

Percutaneous Coronary Intervention in Native Arteries Versus Bypass Grafts in Prior Coronary Artery Bypass Grafting Patients: A Report From the National Cardiovascular Data Registry

OBJECTIVES This study examined a large registry to determine the frequency, predictors, and outcomes of native coronary artery versus bypass graft percutaneous coronary intervention (PCI) in patients with prior coronary artery bypass graft surgery (CABG). BACKGROUND The PCI target vessel and corresponding outcomes in prior CABG patients are poorly studied. METHODS We analyzed the frequency and factors associated with native versus bypass graft PCI in prior CABG patients undergoing PCI between January 1, 2004, and June 30, 2009, in the National Cardiovascular Data Registry (NCDR) CathPCI Registry. Generalized estimating equations logistic regression modeling was used to generate independent variables associated with native versus bypass graft PCI and in-hospital mortality. RESULTS During the study period, PCI in prior CABG patients represented 17.5% of the total PCI volume (300,902 of 1,721,046). The PCI target was a native coronary artery in 62.5% and a bypass graft in 37.5%: saphenous vein graft (SVG) (104,678 [34.9%]), arterial graft (7,517 [2.5%]), or both arterial graft and SVG (718 [0.2%]). Compared with patients undergoing native coronary artery PCI, those undergoing bypass graft PCI had higher-risk characteristics and more procedural complications. On multivariable analysis, several parameters (including graft stenosis and longer interval from CABG) were associated with performing native coronary PCI, and bypass graft PCI was associated with higher in-hospital mortality (adjusted odds ratio: 1.22, 95% confidence interval: 1.12 to 1.32). CONCLUSIONS Most PCIs performed in prior CABG patients are done in native coronary artery lesions. Compared with native coronary PCI, bypass graft PCI is independently associated with higher in-hospital mortality.

Percutaneous coronary intervention versus coronary bypass surgery in United States veterans with diabetes.

OBJECTIVES This study sought to determine the optimal coronary revascularization strategy in patients with diabetes with severe coronary disease. BACKGROUND Although subgroup analyses from large trials, databases, and meta-analyses have found better survival for patients with diabetes with complex coronary artery disease when treated with surgery, a randomized trial comparing interventions exclusively with drug-eluting stents and surgery in patients with diabetes with high-risk coronary artery disease has not yet been reported. METHODS In a prospective, multicenter study, 198 eligible patients with diabetes with severe coronary artery disease were randomly assigned to either coronary artery bypass grafting (CABG) (n = 97) or percutaneous coronary intervention (PCI) with drug-eluting stents (n = 101) and followed for at least 2 years. The primary outcome measure was a composite of nonfatal myocardial infarction or death. Secondary outcome measures included all-cause mortality, cardiac mortality, nonfatal myocardial infarction, and stroke. RESULTS The study was stopped because of slow recruitment after enrolling only 25% of the intended sample size, leaving it severely underpowered for the primary composite endpoint of death plus nonfatal myocardial infarction (hazard ratio: 0.89; 95% confidence interval: 0.47 to 1.71). However, after a mean follow-up period of 2 years, all-cause mortality was 5.0% for CABG and 21% for PCI (hazard ratio: 0.30; 95% confidence interval: 0.11 to 0.80), while the risk for nonfatal myocardial infarction was 15% for CABG and 6.2% for PCI (hazard ratio: 3.32; 95% confidence interval: 1.07 to 10.30). CONCLUSIONS This study was severely underpowered for its primary endpoint, and therefore no firm conclusions about the comparative effectiveness of CABG and PCI are possible. There were interesting differences in the components of the primary endpoint. However, the confidence intervals are very large, and the findings must be viewed as hypothesis generating only. (Coronary Artery Revascularization in Diabetes; NCT00326196).

Prevention of Contrast-Induced AKI: A Review of Published Trials and the Design of the Prevention of Serious Adverse Events following Angiography (PRESERVE) Trial

Contrast-induced AKI (CI-AKI) is a common condition associated with serious, adverse outcomes. CI-AKI may be preventable because its risk factors are well characterized and the timing of renal insult is commonly known in advance. Intravenous (IV) fluids and N-acetylcysteine (NAC) are two of the most widely studied preventive measures for CI-AKI. Despite a multitude of clinical trials and meta-analyses, the most effective type of IV fluid (sodium bicarbonate versus sodium chloride) and the benefit of NAC remain unclear. Careful review of published trials of these interventions reveals design limitations that contributed to their inconclusive findings. Such design limitations include the enrollment of small numbers of patients, increasing the risk for type I and type II statistical errors; the use of surrogate primary endpoints defined by small increments in serum creatinine, which are associated with, but not necessarily causally related to serious, adverse, patient-centered outcomes; and the inclusion of low-risk patients with intact baseline kidney function, yielding low event rates and reduced generalizability to a higher-risk population. The Prevention of Serious Adverse Events following Angiography (PRESERVE) trial is a randomized, double-blind, multicenter trial that will enroll 8680 high-risk patients undergoing coronary or noncoronary angiography to compare the effectiveness of IV isotonic sodium bicarbonate versus IV isotonic sodium chloride and oral NAC versus oral placebo for the prevention of serious, adverse outcomes associated with CI-AKI. This article discusses key methodological issues of past trials investigating IV fluids and NAC and how they informed the design of the PRESERVE trial.

Phase I Drug and Light Dose-Escalation Trial of Motexafin Lutetium and Far Red Light Activation (Phototherapy) in Subjects With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention and Stent Deployment Procedural and Long-Term Results

Background—Motexafin lutetium (MLu; Antrin) is a photosensitizer that is taken up by atherosclerotic plaque and concentrated within macrophages and vascular smooth muscle cells. After photoactivation with far red light, MLu facilitates production of cytotoxic oxygen radicals that mediate apoptosis. We assessed the safety and tolerability of phototherapy (PT) with MLu in patients undergoing percutaneous coronary intervention with stent deployment. Methods and Results—An open-label, phase I, drug and light dose-escalation clinical trial of MLu PT enrolled 80 patients undergoing de novo coronary stent deployment. MLu was administered to 79 patients by intravenous infusion 18 to 24 hours before procedure, and photoactivation was performed after balloon predilatation and before stent deployment. Clinical evaluation, serial quantitative angiography, and intravascular ultrasound were performed periprocedurally and at 6 months follow-up. MLu PT was well tolerated without serious dose-limiting toxicities, and side effects (paresthesia and rash) were minor. No adverse angiographic outcomes were attributed to phototherapy. Conclusions—This study demonstrates that coronary MLu PT seems safe, and the maximum well-tolerated MLu dose and range of tolerated light doses were identified. These data can be used in phase II efficacy trials of MLu PT for the treatment of coronary atherosclerosis or vulnerable plaque.

Frequency and Predictors of Drug-Eluting Stent Use in Saphenous Vein Bypass Graft Percutaneous Coronary Interventions : A Report From the American College of Cardiology National Cardiovascular Data CathPCI Registry

OBJECTIVES We examined a large registry to determine the frequency and factors associated with drug-eluting stents (DES) use in saphenous vein graft (SVG) in contemporary practice. BACKGROUND Prospective trials comparing DES with bare-metal stents in SVG lesions have provided conflicting conclusions regarding safety and efficacy leading to potential variation in stent choice for these lesions. METHODS We analyzed the frequency and factors associated with DES use in patients undergoing SVG stenting from January 1, 2004, to March 31, 2009, in the National Cardiovascular Data Registry. Generalized estimating equations logistic regression modeling was used to generate independent variables associated with DES use in SVGs. RESULTS During the study period, percutaneous coronary intervention (PCI) of a SVG represented 5.7% of the total PCI volume (91,355 of 1,596,966). Of the 84,875 patients who received a SVG stent, a DES was used in 64.5%. From 2005 to 2009, DES use in SVG PCI changed from 80% to 62%. Unfractionated heparin was used in 46%, enoxaparin in 17%, bivalirudin in 42%, and a glycoprotein IIb/IIIa inhibitor in 40% of cases. On multivariable analysis, several parameters (including the period, multivessel PCI, prior PCI, no acute myocardial infarction, and no smoking) were associated with DES use. CONCLUSIONS Currently, DES are used in nearly two-thirds of SVG interventions. Several clinical parameters (such as the period of implantation and the complexity of coronary artery disease) are associated with the decision to implant a DES in these challenging lesions.

Transesophageal magnetic resonance imaging of the aortic arch and descending thoracic aorta in patients with aortic atherosclerosis

OBJECTIVES We sought to determine the feasibility and potential of transesophageal magnetic resonance imaging (TEMRI) for quantifying atherosclerotic plaque burden in the aortic arch and descending thoracic aorta in comparison with transesophageal echocardiography (TEE). BACKGROUND Improved morphologic assessment of atherosclerotic plaque features in vivo is of interest because of the potential for improved understanding of the pathophysiology of plaque vulnerability to rupture and progression to clinical events. Magnetic resonance imaging (MRI) is well suited for atherosclerotic plaque imaging. Performing MRI using a radio frequency (RF) receiver probe placed near the region of interest improves the signal-to-noise ratio (SNR). METHODS High-resolution images of the thoracic aortic wall were obtained by TEMRI in 22 subjects (8 normals, 14 with aortic atherosclerosis). In nine subjects, we compared aortic wall thickness and circumferential extent of atherosclerotic plaque measured by TEMRI versus TEE using a Bland-Altman analysis. Additional studies were performed in a human cadaver with pathology as an independent gold standard for assessment of atherosclerosis. RESULTS In clinical and experimental studies, we found similar measurements for aortic plaque thickness but a relative underestimation of circumferential extent of atherosclerosis by TEE (p = 0.001), due in large part to the lower SNR in the near field. CONCLUSIONS Using TEMRI allows for quantitative assessment of thoracic aortic atherosclerotic plaque burden. This technique provides good SNR in the near field, which makes it a promising approach for detailed characterization of aortic plaque burden.