Intravascular Ultrasound Radiofrequency Research Articles

Associations between circulating microRNAs and coronary plaque characteristics: potential impact from physical exercise.

microRNAs (miRs) are involved in different steps in the development of atherosclerosis and are proposed as promising biomarkers of coronary artery disease (CAD). We hypothesized that circulating levels of miRs were associated with coronary plaque components assessed by radiofrequency intravascular ultrasound (RF-IVUS) before and after aerobic exercise intervention. Thirty-one patients with CAD treated with percutaneous coronary intervention (PCI) previously included in a randomized trial with aerobic interval training (AIT) or moderate continuous training (MCT) as post-PCI intervention were included. Coronary plaque characteristics by grayscale and RF-IVUS and predefined circulating candidate miRs in plasma were analyzed at baseline and follow-up. Associations between miRs and coronary plaque composition, and the potential effect from exercise, were analyzed using linear regression. Circulating levels of miR-15a-5p, miR-30e-5p, miR-92a-3p, miR-199a-3p, miR-221-3p, and miR-222-3p were associated with baseline coronary necrotic core volume. Following exercise intervention, decreased levels of miR-15a-5p, miR-93-5p, and miR-451a, and increased levels of miR-146a-5p were associated with an observed regression of coronary plaque burden. A mirPath prediction tool identified that genes regulated by miR-15a-5p, miR-199a-3p, and miR-30e-5p were significantly overrepresented in pathways related to fatty acid biosynthesis and fatty acid metabolism. This exploratory study demonstrated six miRs associated with coronary necrotic core, a marker of plaque vulnerability. In addition, changes in four miRs were associated with a regression of coronary plaque burden following exercise intervention. These novel findings may identify potential future biomarkers of CAD and coronary plaque composition.

TCT CONNECT-284 Intravascular Ultrasound Radiofrequency Signal Analysis for Simultaneous Assessment of Functional Significance and Structural Abnormality of Intermediate Coronary Artery Lesions

TCT CONNECT-284 Intravascular Ultrasound Radiofrequency Signal Analysis for Simultaneous Assessment of Functional Significance and Structural Abnormality of Intermediate Coronary Artery Lesions

Intravascular ultrasound radiofrequency signal analysis of blood speckles: Physiological assessment of intermediate coronary artery stenosis.

This study aimed to systematically investigate feasibility of radiofrequency intravascular ultrasound (RF-IVUS) analysis of blood signals for assessing functionally significant coronary stenosis. First, in-vivo human study was performed to evaluate 83 intermediate coronary lesions from 75 patients, using 40-MHz RF-IVUS, fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). Average blood integrated-backscatter (IB) values within lumen were measured at proximal and distal segments to the stenosis; ΔIB values between the two sites were calculated. Second, bench-test was performed to assess relationships of blood IB values to blood flow velocity and hematocrit using 40 and 60-MHz RF-IVUS. In in-vivo study, ΔIB values across the stenosis significantly correlated with both FFR (r = -.85, p < .0001) and iFR (r = -.65, p < .0001), which was confirmed in small minimum lumen area (MLA) lesions (MLA <2.0 mm2 ). Receiver operating characteristic curve analyses identified the best cut-off value as 10.06 of ΔIB values for predicting FFR ≤0.8 and iFR ≤0.89 (sensitivity 76.2 and 95.5%, specificity 100 and 82.0%, positive predictive value 100 and 65.6%, negative predictive value 80.4 and 98.0%, accuracy 92.9 and 92.8% for FFR and iFR). Bench-test study also identified that blood IB values exponentially changed as a function of blood flow velocity at any given hematocrit in both 40 and 60-MHz RF-IVUS. This study supports the potential utility of RF-IVUS analysis of blood signals to estimate functional ischemia, demonstrating relationships of blood ΔIB values to FFR and iFR, as well as relationships between blood IB values and flow velocity.

Application of virtual histological intravascular ultrasound in plaque composition assessment of saphenous vein graft diseases.

Objective:Saphenous vein grafts disease (SVGD) is a common complication after coronary artery bypass graft (CABG) and normally treated by percutaneous coronary intervention (PCI). The most common complication after SVG-PCI is slow or no-reflow. It is known that the no-reflow phenomenon occurs in up to 15% of the SVG-PCI and is associated with high risk of major adverse cardiac events (MACEs) and mortality, therefore, it is important to investigate the factors that could predict the clinical outcome of PCI for risk stratification and guiding interventions. In recent years, the spectral analysis of intravascular ultrasound (IVUS) radiofrequency data (virtual histology-IVUS [VH-IVUS]) has been used to provide quantitative assessment on both plaque compositions and morphologic characteristics.Data sources:The PubMed, Embase, and Central databases were searched for possible relevant studies published from 1997 to 2018 using the following index keywords: “Coronary artery bypass grafting,” “Saphenous venous graft disease,” “Virtual histology-intravascular ultrasound,” “Virtual histology-intravascular ultrasound,” and “Percutaneous coronary intervention.”Study selection:The primary references were Chinese and English articles including original studies and literature reviews, were identified and reviewed to summarize the advances in the application of VH-IVUS techniques in situ vascular and venous graft vascular lesions.Results:With different plaque components exhibiting a defined spectrum, VH-IVUS can classify atherosclerotic plaque into four types: fibrous tissue (FT), fibro fatty (FF), necrotic core (NC), and dense calcium (DC). The radiofrequency signal is mathematically transformed into a color-coded representation, including lipid, fibrous tissue, calcification, and necrotic core. Several studies have demonstrated the independent relationship between VH-IVUS–defined plaque classification or plaque composition and MACEs, but a significant association between plaque components and no-reflow after PCI in acute coronary syndrome. In recent years, VH-IVUS are applied to assess the plaque composition of SVGD, based on the similarity of pathophysiological mechanisms between coronary artery disease (CAD) and SVGD, further studies with the larger sample size, the long-term follow-up, multicenter clinical trials may be warranted to investigate the relationship between plaque composition of saphenous vein graft (SVG) by VH-IVUS and clinical outcomes in patients with SVGD undergoing PCI.Conclusions:In degenerative SVG lesions, VH-IVUS found that plaque composition was associated with clinical features, future studies need to explore the relationship between VH-IVUS defined atherosclerotic plaque components and clinical outcomes in SVGD patients undergoing PCI, an innovative prediction tool of clinical outcomes can be created.

SYNTAX score in relation to intravascular ultrasound and near-infrared spectroscopy for the assessment of atherosclerotic burden in patients with coronary artery disease.

The aim of this study was to examine the relationship between the anatomical SYNTAX score (SXscore), derived from all three coronary arteries, and coronary wall pathology measured by radiofrequency intravascular ultrasound (RF-IVUS) and near-infrared spectroscopy (NIRS) in a single non-culprit segment. In patients referred for coronary angiography (N=88) or PCI (N=592) for stable angina or acute coronary syndrome, the SYNTAX score calculator (www.syntaxscore.com) was used to determine the SXscore before PCI, if applicable. RF-IVUS and/or NIRS were performed in a non-stenotic 40 mm study segment following the clinically indicated angiography/PCI. After adjustment for multiple confounders, a higher SXscore was associated with higher segmental plaque volume in the study segment (2.21 mm3 per SXscore point, 95% CI: 0.92-3.50, p-value 0.001), as well as with higher volume of fibrous (0.93 mm3 per point) and fibro-fatty tissue (0.29 mm3 per point). A higher SXscore was also associated with a higher NIRS-derived lipid core burden index (LCBI) in the full study segment (1.35 units per SXscore point, 95% CI: 0.22-2.47, p-value 0.019). Importantly, SXscore correlated with the fatty/fibro-fatty and LCBI signals despite adjusting for plaque burden. In patients with CAD, higher SXscores are associated with higher atherosclerotic burden as assessed by RF-IVUS and NIRS in a single non-stenotic coronary artery segment.

IgM anti-malondialdehyde low density lipoprotein antibody levels indicate coronary heart disease and necrotic core characteristics in the Nordic Diltiazem (NORDIL) study and the Integrated Imaging and Biomarker Study 3 (IBIS-3)

BackgroundCertain immunoglobulins (Ig) are proposed to have protective functions in atherosclerosis.ObjectivesWe tested whether serum levels of IgG and IgM autoantibodies against malondialdehyde low density lipoprotein (MDA-LDL) are associated with clinical coronary heart disease (CHD) and unfavorable plaque characteristics.MethodsNORDIL was a prospective study investigating adverse cardiovascular outcomes in hypertensive patients. IBIS-3 analyzed lesions in a non-culprit coronary artery with <50% stenosis using radiofrequency intravascular ultrasound (RF-IVUS) and near-infrared spectroscopy (NIRS). Imaging was repeated after a median of 386 days on rosuvastatin. Associations of antibodies with incident CHD and imaging parameters were assessed in the two sub-studies respectively.FindingsFrom 10,881 NORDIL patients, 87 had serum sampled at baseline and developed CHD over 4.5 years, matched to 227 controls. Higher titers of IgM anti-MDA-LDL had a protective effect on adverse outcomes, with odds ratio 0.29 (0.11, 0.76; p = 0.012; p = 0.016 for trend). Therefore, the effect was explored at the lesional level in IBIS-3. 143 patients had blood samples and RF-IVUS measurements available, and NIRS was performed in 90 of these. At baseline, IgM anti-MDA-LDL levels had a strong independent inverse relationship with lesional necrotic core volume (p = 0.027) and percentage of plaque occupied by necrotic core (p = 0.011), as well as lipid core burden index (p = 0.024) in the worst 4 mm segment.InterpretationOur study supports the hypothesis that lower circulating levels of IgM anti-MDA-LDL are associated with clinical CHD development, and for the first time relates these findings to atherosclerotic plaque characteristics that are linked to vulnerability.

155 Higher igm anti oxidised ldl antibodies point to favourable plaque characteristics as determined by radio frequency intravascular ultrasound (rf-ivus) and near infrared spectroscopy (nirs) in the integrated imaging and biomarker study 3 (ibis-3)

BackgroundMalondialdehyde (MDA)-LDL is one of the main oxidation products involved in atherosclerosis pathogenesis. IgM antibodies against MDA-LDL have been generally regarded as protecting from atherosclerosis. In contrast, the role of...

Plaque Vulnerability as Assessed by Radiofrequency Intravascular Ultrasound in Patients with Valvular Calcification.

BackgroundCardiac valvular calcification is associated with the overall coronary plaque burden and considered an independent cardiovascular risk and prognostic factor. The purpose of this study was to evaluate the relationship between the presence of valvular calcification and plaque morphology and/or vulnerability.MethodsTransthoracic echocardiography was used to assess valvular calcification in 280 patients with coronary artery disease who underwent radiofrequency intravascular ultrasound (Virtual Histology IVUS, VH-IVUS). A propensity score–matched cohort of 192 patients (n = 96 in each group) was analyzed. Thin-capped fibroatheroma (TCFA) was defined as a necrotic core (NC) >10% of the plaque area with a plaque burden >40% and NC in contact with the lumen for ≥3 image slices. A remodeling index (lesion/reference vessel area) >1.05 was considered to be positive.ResultsPatients were divided into two groups: any calcification in at least one valve (152 patients) vs. no detectable valvular calcification (128 patients). Groups were similar in terms of age, risk factors, clinical diagnosis, and angiographic analysis after propensity score-matched analysis. Gray-scale IVUS analysis showed that the vessel size, plaque burden, minimal lumen area, and remodeling index were similar. By VH-IVUS, % NC and % dense calcium (DC) were greater in patients with valvular calcification (p = 0.024, and p = 0.016, respectively). However, only % DC was higher at the maximal NC site by propensity score-matched analysis (p = 0.029). The frequency of VH-TCFA occurrence was higher depending on the complexity (p = 0.0064) and severity (p = 0.013) of valvular calcification.ConclusionsThere is a significant relationship between valvular calcifications and VH-IVUS assessment of TCFAs. Valvular calcification indicates a greater atherosclerosis disease complexity (increased calcification of the coronary plaque) and vulnerable coronary plaques (higher incidence of VH-TCFA).

The Role of Virtual Histology Intravascular Ultrasound in the Identification of Coronary Artery Plaque Vulnerability in Acute Coronary Syndromes.

Markers of coronary plaque vulnerability, such as a high lipid burden, increased inflammatory activity, and a thin fibrous cap, have been identified in histological studies. In vivo, grayscale intravascular ultrasound (IVUS) provides more in-depth information on coronary artery plaque burden than conventional angiography but is unable to accurately distinguish between noncalcific tissue types within the plaque. An analysis of IVUS radiofrequency backscatter based on spectral pattern recognition, such as virtual histology IVUS, allows detailed scrutiny of plaque composition and classification of coronary lesions. This review discusses the virtual histology IVUS technology and its accuracy in identifying vulnerable plaque features, focusing on its use in predicting patient outcomes after acute coronary syndrome, and its limitations in clinical practice.

Using sound advice-intravascular ultrasound as a diagnostic tool.

Intravascular ultrasound (IVUS) uses varying-frequency catheter-based transducers for assessment of blood vessel dimensions and morphology. Along with advances in the field of interventional cardiology, IVUS technology has progressed in the last two decades. Dedicated training centers in combination with enthusiasm from a new generation of cardiologists complemented by well-established evidence for simplicity, safety and efficacy of IVUS systems have led to increased routine use of this imaging modality. Currently available catheters use sound frequencies in the range of 20–70 MHz, moving from older grayscale IVUS to radiofrequency IVUS (RF-IVUS) and more recently high-definition IVUS (HD-IVUS) devices, some with the ability to differentiate plaque composition.

Integrated Biomarker and Imaging Study 3 (IBIS-3) to assess the ability of rosuvastatin to decrease necrotic core in coronary arteries

Statins are highly effective in reducing major adverse clinical events, but the direct effects on coronary plaque composition remain debatable. Our aim was to mechanistically evaluate the treatment effect of high-intensity statin therapy on compositional coronary plaque changes. The third Integrated Biomarker and Imaging Study (IBIS-3) was a prospective, investigator-initiated, single-centre study. Serial radiofrequency intravascular ultrasound (RF-IVUS) measurements of a predefined non-stenotic segment in a non-culprit coronary artery were performed to evaluate the effect of rosuvastatin (intended dose: 40 mg daily) on necrotic core (NC) volume in patients with stable angina or acute coronary syndrome. Changes in lipid core burden index (LCBI) were evaluated through serial near-infrared spectroscopy (NIRS) imaging in a subset. Serial RF-IVUS (and NIRS) data of a median segment of 41 mm (interquartile range: 32 to 49 mm) were complete in 164 (103) patients. Follow-up measurements were performed at six and 12 months in 30 (26) and 134 (77) patients, respectively. Mean levels of low-density lipoprotein cholesterol decreased by 30%, from 2.49 mmol/l to 1.73 mmol/l at the end of follow-up. High-dose rosuvastatin therapy resulted in a non-significant change of -1.4 mm3 (95% CI: -3.0, 0.1) in NC volume during follow-up (p=0.074). The change in NC percentage of total plaque volume was -1.4% (95% CI: -2.4 to -0.4; p=0.006). A neutral effect was also observed on LCBI. Indications of significant regression of NC volume and LCBI in the highest baseline quartiles were observed, which should cautiously be regarded as hypothesis-generating. High-intensity rosuvastatin therapy during one year resulted in a neutral effect on NC and LCBI within non-stenotic, non-culprit coronary segments with a relatively low atheroma burden. This study has been registered in The Netherlands Trial Register (NTR) nr. 2872.

TCT-163 Physiologic Assessment of Intermediate Coronary Artery Stenosis by Intravascular Ultrasound Radiofrequency Signal Analysis of Blood Speckles: A Comparison with Fractional Flow Reserve and Instantaneous Wave-Free Ratio

Although fractional flow reserve (FFR) is the gold standard in functional assessment of intermediate coronary stenosis, it lacks anatomical information essential for risk stratification of plaque and guidance of PCI. In IVUS, integrated backscatter (IB) values of blood speckles, calculated as the

Reproducibility of intravascular ultrasound radiofrequency data analysis (virtual histology) with a 45-MHz rotational imaging catheter in ex vivo human coronary arteries

BackgroundDespite the frequent use of spectral analysis of intravascular ultrasound radiofrequency data (VH® IVUS) in clinical studies, the assessment for reproducibility using this with high frequency IVUS remains unexplored. PurposeThe aim of this study was to examine the reproducibility of VH IVUS using 45-MHz rotational IVUS in ex vivo human coronary arteries. MethodsData were collected using 45-MHz VH IVUS (Revolution®, Volcano Corporation, San Diego, CA, USA) via a series of pullbacks from eight human coronary artery specimens. Imaging data were analyzed by two independent observers. Intraobserver and interobserver reproducibility were assessed using five pullbacks from five vessels. The intercatheter reproducibility was assessed using three different catheters in each of the five vessels. The intracatheter reproducibility was assessed between the two sequential pullbacks from each of the 15 catheters used in the intercatheter assessment. ResultsGeometrical measurements consistently showed low variability (relative difference <10%) and excellent intraclass correlation coefficients (ICCs), ranging from 0.88 to 1.00. With respect to the compositional measurements, the relative differences were predominantly higher than those of geometrical measurements. In particular, fibrous-fatty area showed a higher relative difference (17.5% in intercatheter assessment) compared to fibrous, necrotic core, and dense calcium areas (6.5%, 8.4%, and 6.4%, respectively). However, each compositional measurement also showed acceptable reproducibility (ICCs ranging from 0.82 to 1.00). ConclusionsThe 45-MHz rotational VH IVUS technology had acceptable reproducibility with respect to geometrical and compositional assessments in ex vivo human coronary arteries. These data are crucial when designing future longitudinal studies addressing geometrical measurements and plaque characterization by 45-MHz VH IVUS.

Antibodies to periodontal pathogens are associated with coronary plaque remodeling but not with vulnerability or burden

ObjectivePrevious studies have suggested positive associations between periodontal infection and cardiovascular disease. We aimed to investigate the associations of circulating antibodies against periodontal pathogens with 1-year cardiovascular outcome, as well as the extent of coronary atherosclerosis, plaque vulnerability and lesion remodeling on intravascular ultrasound (IVUS) imaging. MethodsBetween 2008 and 2011, radiofrequency IVUS imaging of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography. Immunoglobulin G (IgG) and A (IgA) against Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Prevotella intermedia were measured in plasma. ResultsNone of the antibody levels were associated with coronary plaque burden, radiofreqeuncy-IVUS-derived thin-cap fibroatheroma lesion morphology or 1-year incidence of major adverse cardiac events (MACE), which included all-cause mortality, acute coronary syndrome and unplanned coronary revascularization. IgA against A. actinomycetemcomitans, T. forsythia and P. intermedia were inversely associated with extent of positive lesion remodeling (OR for highest versus lowest tertile 0.55, 95%CI 0.35–0.88, p = 0.012; 0.53, 95%CI 0.32–0.87, p = 0.012; and 0.64, 95%CI 0.40–1.02, p = 0.061, respectively). In diabetic patients specifically, IgG against P. gingivalis tended to be associated with coronary plaque burden (p = 0.080), while IgA against P. gingivalis tended to be associated with incident MACE (p = 0.060). ConclusionPlasma IgG and IgA against major periodontal pathogens were not associated with the extent of coronary atherosclerosis (with the exception of a trend in diabetics) nor with coronary plaque vulnerability. IgA against periodontal pathogens were inversely associated with extent of coronary remodeling. Altogether, these results do not add evidence for a substantial role of systemic exposure to periodontal pathogens in coronary artery disease.

Coronary Atheroma Regression and Plaque Characteristics Assessed by Grayscale and Radiofrequency Intravascular Ultrasound After Aerobic Exercise

The aim of the present study was to investigate effects of aerobic interval training (AIT) versus moderate continuous training (MCT) on coronary atherosclerosis in patients with significant coronary artery disease on optimal medical treatment. Thirty-six patients were randomized to AIT (intervals at ≈ 90% of peak heart rate) or MCT (continuous exercise at ≈ 70% of peak heart rate) 3 times a week for 12 weeks after intracoronary stent implantation. Grayscale and radiofrequency intravascular ultrasounds (IVUS) were performed at baseline and follow-up. The primary end point was the change in plaque burden, and the secondary end points were change in necrotic core and plaque vulnerability. Separate lesions were classified using radiofrequency IVUS criteria. We demonstrated that necrotic core was reduced in both groups in defined coronary segments (AIT -3.2%, MCT -2.7%, p <0.05) and in separate lesions (median change -2.3% and -0.15 mm(3), p <0.05). Plaque burden was reduced by 10.7% in separate lesions independent of intervention group (p = 0.06). No significant differences in IVUS parameters were found between exercise groups. A minority of separate lesions were transformed in terms of plaque vulnerability during follow-up with large individual differences between and within patients. In conclusion, changes in coronary artery plaque structure or morphology did not differ between patients who underwent AIT or MCT. The combination of regular aerobic exercise and optimal medical treatment for 12 weeks induced a moderate regression of necrotic core and plaque burden in IVUS-defined coronary lesions.

Relation of C-Reactive Protein to Coronary Plaque Characteristics on Grayscale, Radiofrequency Intravascular Ultrasound, and Cardiovascular Outcome in Patients With Acute Coronary Syndrome or Stable Angina Pectoris (from the ATHEROREMO-IVUS Study)

The relation between C-reactive protein (CRP) and coronary atherosclerosis is not fully understood. This study aims to investigate the associations among high-sensitivity CRP, coronary plaque burden, and the presence of high-risk coronary lesions as measured by intravascular ultrasound (IVUS) and 1-year cardiovascular outcome. Between 2008 and 2011, grayscale and virtual histology IVUS imaging of a nonculprit coronary artery was performed in 581 patients who underwent coronary angiography for acute coronary syndrome (ACS) or stable angina pectoris. Primary end point consisted of 1-year major adverse cardiac events (MACEs), defined as all-cause mortality, ACS, or unplanned coronary revascularization. After adjustment for established cardiac risk factors, baseline CRP levels were independently associated with higher coronary plaque burden (p = 0.002) and plaque volume (p = 0.002) in the imaged coronary segment. CRP was also independently associated with the presence of large lesions (plaque burden ≥70%; p = 0.030) but not with the presence of stenotic lesions (minimal luminal area ≤4.0 mm(2); p = 0.62) or IVUS virtual histology-derived thin-cap fibroatheroma lesions (p = 0.36). Cumulative incidence of 1-year MACE was 9.7%. CRP levels >3 mg/L were independently associated with a higher incidence of MACE (hazard ratio 2.17, 95% confidence interval [CI] 1.01 to 4.67, p = 0.046) and of all-cause mortality and ACS only (hazard ratio 3.58, 95% CI 1.04 to 13.0, p = 0.043), compared with CRP levels <1 mg/L. In conclusion, in patients who underwent coronary angiography, high-sensitivity CRP is a marker of coronary plaque burden but is not related to the presence of virtual histology-derived thin-cap fibroatheroma lesions and stenotic lesions. CRP levels >3 mg/L are predictive for adverse cardiovascular outcome at 1 year.

Reproducibility of grayscale and radiofrequency IVUS data acquisition in stented coronary arteries

Objectives. Variability in data acquisition from intervened coronary arteries could represent a source of error that has implications for the design of serial stent studies. We assessed inter-pullback reproducibility of volumetric grayscale and radiofrequency intravascular ultrasound (IVUS) data in stented coronary arteries. Design. Fifteen patients with coronary artery lesions treated with stent implantation were included and examined with two separate pullbacks using the Eagle Eye Gold-phased array 20 MHz IVUS catheter (Volcano). The arteries were divided into five segments, giving a total of 150 sub-segments for analyses. Matching of frames was performed using landmarks that were clearly visible in coronary angiography and intravascular pullbacks. Data were analyzed off-line at an independent Corelab. Results. The inter-pullback reproducibility of geometrical data was very good for non-stented segments with relative differences less than 5% between pullbacks for lumen-, vessel-, and plaque volumes. For stented segments reproducibility was poorer with relative differences between pullbacks in the range of 5–10%. The inter-pullback reproducibility of compositional data demonstrated large standard deviations of relative differences, indicating a weaker agreement. Conclusions. Agreements between pullbacks were weaker in stented than those in non-stented segments. Based on our data, future longitudinal IVUS studies in intervened vessels should account for a variability of 5–10% attributed to the acquisition of images.

Relation of C-Reactive Protein Levels to Instability of Untreated Vulnerable Coronary Plaques (from the PROSPECT Study)

C-reactive protein (CRP) levels predict adverse coronary events, but it is uncertain if they predict the burden or stability of vulnerable coronary plaques. In the Providing Regional Observations to Study Predictors of Events in the Coronary Tree study, 697 patients with acute coronary syndromes underwent percutaneous coronary intervention followed by 3-vessel angiography, gray-scale intravascular ultrasound (IVUS), and radiofrequency IVUS. Major adverse cardiac events (MACE) during 3years of follow-up were adjudicated to initially treated culprit lesions or to untreated nonculprit lesions (NCLs). NCLs at greatest risk of causing subsequent MACE had plaque burden ≥70%, minimal luminal area ≤4.0mm(2), and/or thin-cap fibroatheroma morphology. Here, we examine the interaction of high-risk NCLs with CRP levels, which were measured at presentation, 1month, and 6months, then categorized at each time as normal (<3mg/L), elevated (3 to 10mg/L), or very elevated (>10mg/L). We found that patients with elevated CRP levels at any time did not have more high-risk NCLs; however, untreated high-risk NCLs were more likely to cause subsequent MACE in patients with very elevated compared with normal 6-month CRP levels (for thin-cap fibroatheromas, 13.8% vs 1.9%, p= 0.0003; for lesions with minimal luminal area ≤4.0mm(2), 15.6% vs 2.2%, p <0.0001). As expected, patients with very elevated 6-month CRP levels had higher rates of subsequent NCL-related MACE (19.0% vs 7.2%, p= 0.039). In conclusion, the higher rates of NCL-related MACE in post-acute coronary syndrome patients with very elevated CRP levels may reflect greater instability of high-risk NCLs, rather than a larger burden of such lesions.

Long-term effects of maximally intensive statin therapy on changes in coronary atheroma composition: insights from SATURN

To evaluate the effect of long-term maximally intensive statin therapy on indices of coronary atheroma composition in a randomized trial, and how these changes relate to modifications of serum lipoproteins and systemic inflammation. The Study of coronary Atheroma by inTravascular Ultrasound: the effect of Rosuvastatin vs. atorvastatiN (SATURN) employed serial intravascular ultrasound (IVUS) measures of coronary atheroma in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg daily for 24 months. Seventy-one patients underwent serial assessment of indices of plaque composition by spectral analysis of the radiofrequency IVUS signal. Changes in low-density lipoprotein cholesterol [LDL-C; -52 (-72, -33) mg/dL, P < 0.001], C-reactive protein [CRP -0.2 (-1, 0.1) mg/L, P = 0.01], and high-density lipoprotein cholesterol [HDL-C; +2.8 (-0.3, 7.8) mg/dL, P < 0.001] were associated with regression of percent atheroma volume (PAV: -1.6 ± 3.6%, P < 0.001). A reduction in estimated fibro-fatty tissue volume accompanied atheroma regression (P < 0.001), while dense calcium tissue volume increased (P = 0.002). There were no changes in fibrous or necrotic core tissue volumes. Volumetric changes in necrotic core tissue correlated with on-treatment HDL-C (r = -0.27, P = 0.03) and CRP (r = 0.25, P = 0.03) levels. A per-lesion analysis showed a reduction in the number of pathological intimal thickening lesions (defined by ≥3 consecutive IVUS frames containing PAV of ≥40%, predominantly fibro-fatty plaque, with <10% confluent necrotic core and <10% confluent dense calcium) at follow-up (67 vs. 38, P = 0.001). Fibroatheromas and fibrotic lesions remained static in number. Changes in indices of atheroma composition accompany regression of coronary atheroma with maximally intensive statin therapy, and associate with anti-inflammatory effects of statins. NCT000620542.

Young coronary artery disease in patients undergoing percutaneous coronary intervention

BACKGROUND AND OBJECTIVESUnderstanding the nature and pattern of young coronary artery disease (CAD) is important due to the tremendous impact on these patients’ socio-economic and physical aspect. Data on young CAD in the southeast Asian region is rather patchy and limited. Hence we utilized our National Cardiovascular Disease Database (NCVD)—Percutaneous Coronary Intervention (PCI) Registry to analyze young patients who underwent PCI in the year 2007 to 2009.DESIGN AND SETTINGSThis is a retrospective study of all patients who had undergone coronary angioplasty from 2007 to 2009 in 11 hospitals across Malaysia.METHODSData were obtained from the NCVD—PCI Registry, 2007 to 2009. Patients were categorized into 2 groups—young and old, where young was defined as less than 45 years for men and less than 55 years for women and old was defined as more than or equals to 45 years for men and more than or equals to 55 years for women. Patients’ baseline characteristics, risk factor profile, extent of coronary disease and outcome on discharge, and 30-day and 1-year follow-up were compared between the 2 groups.RESULTSWe analyzed 10 268 patients, and the prevalence of young CAD was 16% (1595 patients). There was a significantly low prevalence of Chinese patients compared to other major ethnic groups. Active smoking (30.2% vs 17.7%) and obesity (20.9% vs 17.3%) were the 2 risk factors more associated with young CAD. There is a preponderance toward single vessel disease in the young CAD group, and they had a favorable clinical outcome in terms of all-cause mortality at discharge (RR 0.49 [CI 0.26–0.94]) and 1-year follow-up (RR 0.47 [CI 0.19–1.15]).CONCLUSIONWe observed distinctive features of young CAD that would serve as a framework in the primary and secondary prevention of the early onset CAD.