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.

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.