Clinical Predictors for Lack of Favorable Vascular Response to Statin Therapy in Patients With Coronary Artery Disease: A Serial Optical Coherence Tomography Study.

BACKGROUND: Previous studies have demonstrated that statin therapy improves cardiac outcomes, probably by stabilizing thin-cap fibroatheroma in patients with coronary artery disease. However, major adverse cardiac events still occur in some patients, despite statin therapy. The aim of this study is to identify clinical predictors for the lack of a favorable vascular response to statin therapy in patients with coronary artery disease. METHODS AND RESULTS: A total of 140 nonculprit plaques from 84 patients with coronary artery disease who were treated with a statin and had serial optical coherence tomography imaging (median interval, 6.3 months) were included. Thin-cap area (fibrous cap thickness, <200 µm) was measured using a novel 3-dimensional computer-aided algorithm. Overall, the thin-cap area significantly decreased from baseline (median, 2.852 mm2; 25th-75th percentile, 1.023-6.157 mm2) to follow-up (median, 1.210 mm2; 25th-75th percentile, 0.250-3.192 mm2; P<0.001), and low-density lipoprotein cholesterol significantly decreased from baseline (mean±SD, 92.9±30.1 mg/dL) to follow-up (mean±SD, 76.3±23.3 mg/dL; P<0.001). The general linear model with multiple predictor variables revealed that the thin-cap area was significantly higher in patients with chronic kidney disease than in those without it (regression coefficient b, 1.691 mm2; 95% confidence interval, 0.350-3.033 mm2; P=0.013) and lower in patients with acute coronary syndrome (regression coefficient b, -1.535 mm2; 95% confidence interval, -2.561 to -0.509 mm2; P=0.003). CONCLUSIONS: Chronic kidney disease is an independent predictor for the lack of a favorable vascular response to statin therapy, whereas acute coronary syndrome is an independent predictor for favorable vascular response to statin therapy. These findings should be further warranted in future prospective studies. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01110538.

Morphological predictors for no reflow phenomenon after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction caused by plaque rupture.

AIMS: Myocardial no reflow after percutaneous coronary intervention (PCI) is associated with poor outcome. Patients with ST-segment elevation myocardial infarction (STEMI) caused by plaque rupture are at high risk for no reflow. However, specific morphologic characteristics associated with no reflow are unknown in this population. The aim of this study is to identify the morphological characteristics of culprit plaques associated with no reflow in patients with STEMI caused by plaque rupture using both optical coherence tomography (OCT) and intravascular ultrasound (IVUS). METHODS AND RESULTS: We enrolled 145 patients with STEMI who underwent both OCT and IVUS within 12 h of symptom onset. Among these patients, we excluded those with plaque erosion and calcified nodule and included 72 patients who had plaque rupture as an underlying mechanism for STEMI. Myocardial no reflow, defined as Thrombolysis in Myocardial Infarction flow grade 0-2 and/or myocardial blush grade 0-1 after PCI, was observed in 28 patients (38.9%). Onset to recanalization time was similar between the groups with and without no reflow. Receiver-operating curve analysis revealed OCT-derived lipid index > 3500 [area under curve (AUC) 0.77, P < 0.001] and IVUS-derived plaque burden > 81.5% (AUC 0.70, P = 0.002) were the best discriminators for myocardial no reflow. CONCLUSION: No reflow occurred in nearly 40% of patients with STEMI caused by plaque rupture. Large lipid index and plaque burden were critical morphological discriminators between no reflow and normal flow.

Prevalence and Predictors of Multiple Coronary Plaque Ruptures: In Vivo 3-Vessel Optical Coherence Tomography Imaging Study.

OBJECTIVE: Plaque rupture may be the local expression of a widespread coronary instability. This study aimed to investigate: (1) the prevalence and characteristics of nonculprit plaque rupture; (2) the pancoronary atherosclerotic phenotype in patients with and without nonculprit plaque rupture; and (3) the prevalence and predictors of multiple plaque ruptures. APPROACH AND RESULTS: Six hundred and seventy-five nonculprit plaques from 261 patients (34 acute myocardial infarction, 73 unstable angina pectoris, and 154 stable angina pectoris) were analyzed by 3-vessel optical coherence tomography. Nonculprit plaque ruptures were identified in 51 patients (20%). Patients with nonculprit plaque ruptures had higher prevalence of thin-cap fibroatheroma (51% versus 13%; P<0.001) in the 3 major epicardial coronary vessels. Multiple plaque ruptures were observed in 20% of patients (38% acute myocardial infarction versus 10% unstable angina pectoris versus 19% stable angina pectoris; P=0.042). Thin-cap fibroatheroma, intimal vasculature, and macrophages were independent morphological predictors of multiple plaque ruptures, whereas acute myocardial infarction and chronic kidney disease were independent clinical predictors. Patients with nonculprit plaque ruptures showed higher 1-year rates of nontarget lesion revascularization (11.8% versus 4.4%; P=0.039). CONCLUSIONS: Nonculprit plaque ruptures were observed in 20% of patients with coronary artery disease and were associated with pancoronary vulnerability and higher 1-year revascularization rate.

Changes in coronary plaque morphology in patients with acute coronary syndrome versus stable angina pectoris after initiation of statin therapy.

OBJECTIVES: The aim of this study was to examine coronary plaque morphology after initiation of statins and compare changes in plaque morphology in patients presenting with acute coronary syndrome (ACS) versus stable angina pectoris (SAP). BACKGROUND: ACS is associated with a pan-inflammatory state, and intraplaque features of inflammation correlate with coronary plaque progression. Statins have known anti-inflammatory properties that may contribute toward their beneficial cardiovascular effects. METHODS: Sixty-nine statin-naive patients (ACS, n=55; SAP, n=14) underwent baseline imaging with optical coherence tomography and intravascular ultrasound. Repeat imaging was performed at 6 and 12 months. A total of 97 nonculprit plaques were analyzed (ACS, n=74; SAP, n=23). RESULTS: Fibrous cap thickness increased in both ACS and SAP patients (all P<0.001 compared with the baseline); the ACS group showed greater percent change in fibrous cap thickness at 12 months (192.8±148.9% in ACS vs. 128.2±88.7% in SAP, P=0.018). The ACS group also showed a significant decrease in plaque microvessels (44.6% at baseline vs. 26.6% at 12 months, P=0.0386). CONCLUSION: Compared with patients with SAP, patients presenting with ACS show more favorable changes in plaque morphology after starting statin treatment. This supports a potential additive benefit of statins in the inflammatory state of ACS and reaffirms the clinical importance of statin therapy for coronary atherosclerosis.

Associations between the Framingham Risk Score and coronary plaque characteristics as assessed by three-vessel optical coherence tomography.

OBJECTIVES: This study sought to explore the association between the Framingham Risk Score (FRS) and coronary plaque characteristics assessed by optical coherence tomography (OCT) imaging. BACKGROUND: Clinical prediction models are useful for identifying high-risk patients. However, coronary events often occur in individuals estimated to be at low risk. METHODS: A total of 254 patients with coronary artery disease who underwent three-vessel OCT were divided into tertiles according to FRS. Nonculprit plaque characteristics were compared among the three groups. RESULTS: A total of 663 plaques were analyzed. FRS was significantly associated with calcification [37% (low FRS) vs. 46% (intermediate FRS) vs. 70% (high FRS); P<0.001] and neovascularization [39% (low FRS) vs. 41% (intermediate FRS) vs. 56% (high FRS); P<0.001], but not with lipid-rich plaques or thin-cap fibroatheroma (TCFA). On multivariate analysis, FRS was an independent predictor of the presence of both calcification and neovascularization. There were no deaths, two acute myocardial infarctions, and 15 nontarget lesion revascularizations at the 1-year follow-up. The event rate increased progressively across FRS tertiles [2.4% (low FRS) vs. 7.1% (intermediate FRS) vs. 8.6% (high FRS); P=0.186]. The c-statistic for FRS to predict future clinical events was 0.628 (95% confidence interval, 0.500-0.757). The addition of both calcification and TCFA to FRS provided incremental prognostic value [c-statistics: 0.761 (95% confidence interval, 0.631-0.890)]. CONCLUSION: The present study showed significant associations between FRS and the presence of coronary calcification and neovascularization in nonculprit plaques. The combination of FRS and OCT-detected calcifications and TCFA provides improved prognostic ability in identifying patients with known coronary artery disease who are at risk of recurrent events.

Coronary Calcification and Plaque Vulnerability: An Optical Coherence Tomographic Study.

BACKGROUND: Spotty superficial calcium deposits have been implicated in plaque vulnerability based on previous intravascular imaging studies. Biomechanical models suggest that microcalcifications between 5 and 65 µm in diameter can intensify fibrous cap stress, promoting plaque rupture. However, the 100- to 200-µm resolution of intravascular ultrasound limits its ability to discriminate single calcium deposits from clusters of smaller deposits, and a previous optical coherence tomographic investigation evaluated calcifications within a long segment of artery, which may not truly reflect the mechanics involved in potentiating focal plaque rupture. METHODS AND RESULTS: Detailed optical coherence tomographic assessment of coronary calcification at the culprit plaque (10-mm length) was performed in 53 patients with acute ST-segment-elevation myocardial infarction mediated by plaque rupture and 55 patients with stable angina pectoris. The number and longitudinal length of individual calcium deposits were recorded. Cross-sectional images were analyzed every 1 mm for calcium arc and depth, and these quantitative parameters were used to define individual deposits as spotty, large, and superficial. There was no significant difference between ST-segment-elevation myocardial infarction mediated by plaque rupture and stable angina pectoris groups in the number of total (P=0.58), spotty (P=0.87), or large calcium deposits (P=0.27). Minimum calcium depth was similar between groups (P=0.27), as was the number of superficial deposits (P=0.35 using a 65-µm depth threshold and P=0.84 using a 100-µm depth threshold). CONCLUSIONS: The number and pattern of culprit plaque calcifications did not differ between patients presenting with ST-segment-elevation myocardial infarction mediated by plaque rupture versus stable angina pectoris. The optical coherence tomographic assessment of coronary calcification may not be a useful marker of local plaque vulnerability as previously suspected. REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01110538.

Incidence and Morphological Predictors of Intrastent Coronary Thrombus After Drug-Eluting Stent Implantation (from a Multicenter Registry).

The mechanisms responsible for late and very late stent thrombosis remain incompletely understood. This study aimed to evaluate the incidence and morphologic predictors of intrastent thrombus in patients after drug-eluting stent (DES) implantation using optical coherence tomography (OCT). A total of 208 patients with 262 DES who underwent follow-up OCT examination >6 months after DES implantation were included. The detailed vascular morphology including characteristics of neointima was analyzed. Thrombus was identified in 24 patients (11.5%) 11 months after DES implantation. Minimal lumen cross-sectional area was significantly smaller in the thrombus group than in the nonthrombus group (2.9 ± 1.7 vs 4.6 ± 2.0 mm(2); p <0.001). No difference was found in the frequency of uncovered or malapposed struts between the 2 groups. Thin-cap fibroatheroma (20.6% vs 0.1%; p <0.001) and heterogeneous neointima (22.2% vs 9.0%; p = 0.001) were more frequently detected in the thrombus group compared to the nonthrombus group. Second-generation DES showed lower incidence of thrombus, uncovered struts, and extrastent lumen compared with first-generation DES. In conclusion, the present OCT study revealed that smaller lumen cross-sectional area and neointimal morphology are important factors associated with intrastent thrombus. Second-generation DES demonstrated improved arterial healing and a lower incidence of intrastent thrombus compared with first-generation DES.

Clinical utility of quantitative bright spots analysis in patients with acute coronary syndrome: an optical coherence tomography study.

To investigate the clinical significance of bright spots in coronary plaque detected by optical coherence tomography (OCT) in patients with coronary artery disease. We identified 112 patients [acute coronary syndromes (ACS): n = 50, stable angina pectoris (SAP): n = 62] who underwent OCT imaging of the culprit lesion. A novel OCT algorithm was applied to detect bright spots representing the juxtaposition of a variety of plaque components including macrophages. The density of bright spots within the most superficial 250 µm of the vessel wall was measured at the site of culprit lesion. Bright spot density in the culprit lesion was significantly higher in patients presenting with ACS compared to those presenting with SAP (0.51 ± 0.43% vs. 0.37 ± 0.26%, P = 0.04), particularly in the subgroup with ruptured culprit plaque (0.59 ± 0.52%). Thin-cap fibroatheroma (TCFA) was associated with a trend towards a higher density of bright spots compared to non-TCFA plaques (0.57 ± 0.50% vs. 0.41 ± 0.31%, P = 0.08). Similar results were also obtained within 1000 µm depth. Positive linear correlation was demonstrated between bright spot density and hsCRP level (r = 0.45, P = 0.002). Using a novel algorithm, we demonstrated a significantly higher density of bright spots in the culprit lesions of patients presenting with ACS, particularly in case of plaque rupture, compared to those presenting with SAP. The density of bright spots also correlates with inflammatory status. These results suggest that the quantitative assessment of bright spot density may be useful in evaluating plaque vulnerability.

Incidence and Clinical Significance of Poststent Optical Coherence Tomography Findings: One-Year Follow-Up Study From a Multicenter Registry.

BACKGROUND: Optical coherence tomography (OCT) was recently introduced to optimize percutaneous coronary intervention. However, the exact incidence and significance of poststent OCT findings are unknown. METHODS AND RESULTS: A total of 900 lesions treated with 1001 stents in 786 patients who had postprocedure OCT imaging were analyzed to evaluate the incidence of poststent OCT findings and to identify the OCT predictors for device-oriented clinical end points, including cardiac death, target vessel-related myocardial infarction, target lesion revascularization, and stent thrombosis. Patients were followed up to 1 year. Stent edge dissection was detected in 28.7% of lesions, and incomplete stent apposition was detected in 39.1% of lesions. The incidences of smooth protrusion, disrupted fibrous tissue protrusion, and irregular protrusion were 92.9%, 61.0%, and 53.8%, respectively. Small minimal stent area, defined as a lesion with minimal stent area <5.0 mm(2) in a drug-eluting stent or <5.6 mm(2) in a bare metal stent, was observed in 40.4% of lesions. One-year device-oriented clinical end points occurred in 33 patients (4.5%). Following adjustment, irregular protrusion and small minimal stent area were independent OCT predictors of 1-year device-oriented clinical end points (P=0.003 and P=0.012, respectively). CONCLUSIONS: Abnormal poststent OCT findings were frequent. Irregular protrusion and small minimal stent area were independent predictors of 1-year device-oriented clinical end points, which were primarily driven by target lesion revascularization.

A Combined Optical Coherence Tomography and Intravascular Ultrasound Study on Plaque Rupture, Plaque Erosion, and Calcified Nodule in Patients With ST-Segment Elevation Myocardial Infarction: Incidence, Morphologic Characteristics, and Outcomes After Percutaneous Coronary Intervention.

OBJECTIVES: This study sought to evaluate the incidence of plaque rupture (PR), plaque erosion (PE), and calcified nodule (CN) using optical coherence tomography (OCT) in patients with ST-segment elevation myocardial infarction (STEMI); to compare detailed morphologic plaque characteristics of PR, PE, and CN with optical coherence tomography and intravascular ultrasound; and to compare the post-procedure outcomes among PR, PE, and CN. BACKGROUND: The incidence and detailed morphologic characteristics of PR, PE, and CN in STEMI patients and their outcome after percutaneous coronary intervention (PCI) are unknown. METHODS: A total of 112 STEMI patients who underwent PCI within 24 h [corrected] from symptom onset were included. Both optical coherence tomography and intravascular ultrasound were performed following aspiration thrombectomy. RESULTS: The incidence of PR, PE, and CN was 64.3%, 26.8%, and 8.0%, respectively. PE and CN, compared with PR, had more fibrous plaque (p < 0.001 and p < 0.001) and less thin-cap fibroatheroma (p < 0.001 and p < 0.001) as well as smaller plaque burden (p = 0.003 and p = 0.001) and remodeling index (p = 0.003 and p < 0.001). PE had greater plaque eccentricity index than PR and CN (p < 0.001 and p < 0.001). CN had greater calcified arc and shallower calcium than PR (p < 0.001 and p < 0.001) or PE (p < 0.001 and p < 0.001). More than one-half of CN had negative remodeling. PE had a lower incidence of no-reflow phenomenon after PCI than PR (p = 0.011). CONCLUSIONS: PE was the underlying mechanism in one-fourth of STEMI. PE was characterized by eccentric fibrous plaque. CN was characterized by superficial large calcium and negative remodeling. PE was associated with less microvascular damage after PCI.

Impacts of lesion angle on incidence and distribution of acute vessel wall injuries and strut malapposition after drug-eluting stent implantation assessed by optical coherence tomography.

AIMS: To investigate the impact of lesion angle on the incidence and distribution of acute vessel wall injuries and incomplete stent apposition (ISA) following second-generation drug-eluting stent (DES) implantation using optical coherence tomography (OCT). Several ex vivo studies demonstrated that angled arterial walls are exposed to imbalanced mechanical stress from deployed stents. METHODS AND RESULTS: We included 243 lesions treated with a single DES (148 everolimus-eluting stent and 95 zotarolimus-eluting stent). Angled lesions were defined as lesions with angle ≥45° on an angiogram (n = 58). The vessel wall injuries and ISA were evaluated by OCT. The results were compared with non-angled lesions (<45°, n = 185). The incidence of instent dissection, thrombus, and ISA was significantly higher in the angled group than in the non-angled group (84.5 vs. 63.2%, P < 0.01; 55.2 vs. 35.1%, P < 0.01; 75.9 vs. 44.9%, P < 0.001, respectively). In the angled group, the normalized tissue protrusion volume around the centre of angle (6.59 ± 6.81, mm(3) × 10(2)) was higher than in the distal sub-segment (2.21 ± 2.87, mm3 × 10(2), P < 0.001), in the proximal sub-segment (4.14 ± 5.34, mm3 × 10(2), P = 0.02), and in the non-angled group (3.30 ± 2.81, mm3 × 10(2), P < 0.001). The incidence of major adverse cardiac events within 12 months was similar between the groups. CONCLUSIONS: Angled coronary lesions had a higher incidence rate of OCT-detected vessel wall injuries and ISA compared with non-angled lesions following second-generation DES implantation. Further studies are needed to understand the long-term clinical significance of these findings.

Causes, assessment, and treatment of stent thrombosis--intravascular imaging insights.

Stent thrombosis is a rare, but serious, complication of percutaneous coronary intervention and is associated with severe morbidity and mortality. In addition to clinical and pathological studies, intravascular imaging has advanced our understanding of the mechanisms underlying stent thrombosis. In particular, intravascular imaging has been used to study stent underexpansion, malapposition, uncovered struts, and neoatherosclerosis as risk factors for stent thrombosis. Intravascular ultrasonography and optical coherence tomography can be used to guide stent implantation and minimize the risk of stent thrombosis. Additionally, optical coherence tomography offers the unique potential to tailor treatment of stent thrombosis to address the specific mechanism underlying the thrombotic event. Bioresorbable stent technologies have been introduced with the goal of further reducing the incidence of stent thrombosis, and intravascular imaging has had an integral role in the development and assessment of these new devices. In this Review, we present insights gained through intravascular imaging into the causes of stent thrombosis, and the potential utility of intravascular imaging in the optimization of stent deployment and treatment of stent thrombosis events.

Fundamentals of Optical Coherence Tomography: Image Acquisition and Interpretation.

Optical coherence tomography (OCT) is an intravascular imaging modality that enables high-resolution cross-sectional imaging of coronary arteries in vivo. With resolution that is a 10-fold improvement compared with intravascular ultrasonography, OCT can facilitate detailed plaque characterization. This article introduces the basic principles of OCT image acquisition and interpretation. Qualitative analysis entails the evaluation of plaque morphology, including features associated with plaque vulnerability to rupture. Quantitative analysis and recognition of OCT image artifacts are also discussed.

Imaging methods for detection of chemotherapy-associated cardiotoxicity and dysfunction.

Survival in cancer has improved, shifting some of the focus of care to minimizing the long term complications of cancer therapy. Cardiovascular disease is a leading long-term cause of morbidity and mortality in patients who survive cancer. In the review we will focus on imaging techniques that are used to detect the cardiovascular consequences of chemotherapy. We will differentiate cardiotoxicity and cardiac injury from cardiac dysfunction and cardiomyopathy. We will discuss the current clinical measures that are used to monitor patients, the limitations of each technique, and then detail research into novel methods for tracking and detecting the cardiac toxicity and cardiac dysfunction that may occur as a result of chemotherapy.

Radiation-associated valvular heart disease.

Therapeutic ionizing radiation, such as that used in the treatment of Hodgkin's lymphoma, can cause cardiac valvular damage that may take several years to manifest as radiation-associated valvular heart disease. Treatment can be complicated by comorbid radiation injury to other cardiac and mediastinal structures that lead to traditional surgical valve replacement or repair becoming high-risk. A representative case is presented that demonstrates the complexity of radiation-associated valvular heart disease and its successful treatment with percutaneous transcatheter valve replacement. The prevalence and pathophysiologic mechanism of radiation-associated valvular injury are reviewed. Anthracycline adjuvant therapy appears to increase the risk of valvular fibrosis. Left-sided heart valves are more commonly affected than right-sided heart valves. A particular pattern of calcification has been noted in some patients, and experimental data suggest that radiation induction of an osteogenic phenotype may be responsible. A renewed appreciation of the cardiac valvular effects of therapeutic ionizing radiation for mediastinal malignancies is important, and the treatment of such patients may be assisted by the development of novel, less-invasive approaches.

Extracellular cholesterol-rich microdomains generated by human macrophages and their potential function in reverse cholesterol transport.

Previous studies have shown that cholesterol in atherosclerotic plaques is present in both intracellular and extracellular forms. In the current study, we investigated a mechanism for extracellular cholesterol accumulation and examined the capacity of this pool of cholesterol to be removed by cholesterol acceptors, a step in reverse cholesterol transport. Human monocyte-derived macrophages differentiated with macrophage-colony stimulating factor were incubated with acetylated LDL to allow cholesterol enrichment and processing. These macrophages were subsequently labeled with a monoclonal antibody that specifically detects ordered cholesterol arrays, revealing the presence of unesterified cholesterol-rich microdomains on the cell surfaces and in the extracellular matrix. Similar unesterified cholesterol-rich microdomains were present in human atherosclerotic plaques. Actin microfilaments functioned in microdomain deposition or maintenance, and Src family kinases regulated transfer of these microdomains from the cell surface onto the extracellular matrix. Mediators of reverse cholesterol transport, apolipoprotein A-I (apoA-I), and HDL were capable of removing these extracellular un-esterified cholesterol-rich microdomains. However, apoA-I removed the microdomains only when macrophages were present. ApoA-I removal of microdomains was blocked by glyburide and inhibitor of ATP-binding cassette transporter A1 (ABCA1) function. In summary, cultures of cholesterol-enriched human monocyte-derived macrophages generate extracellular unesterified cholesterol-rich microdomains, which can subsequently be removed by cholesterol acceptors and therefore potentially function in reverse cholesterol transport.