Relationship between tissue characterization with 40 MHz intravascular ultrasound imaging and 64-slice computed tomography

BackgroundIdentification of coronary plaque composition is important for selecting the treatment strategy, and 64-slice computed tomography (CT) is a noninvasive method of characterizing atherosclerotic plaques. However, the correlation between plaque characteristics detected by CT and intravascular ultrasound (IVUS) is not clear. A 40 MHz IVUS imaging system (iMap-IVUS) has recently been developed to evaluate plaque composition. The aim of this study was to compare iMap-IVUS with 64-slice CT angiography for the characterization of non-calcified coronary plaques.Methods and resultsBoth 64-slice CT angiography and iMap-IVUS were performed in 19 patients (38 plaques). CT values were measured as Hounsfield units (HU) in circular regions of interest (ROI) drawn on the plaques. The iMap-IVUS system analyzed coronary plaques as fibrotic, lipidic, necrotic, or calcified tissue based on the radiofrequency spectrum.A positive correlation was found between CT values and the percentage of fibrotic plaque (r = 0.34, p = 0.036) or calcified plaque (r = 0.40, p = 0.011). Conversely, a negative correlation was found between CT values and the percentage of lipidic plaque (r = ?0.41, p = 0.01), or necrotic plaque (r = ?0.41, p = 0.01).ConclusionsGood correlations were observed between the characteristics of non-calcified plaque determined by iMap-IVUS and the CT values of plaque detected by 64-slice CT scanning.     

Topological Data Analysis of Coronary Plaques Demonstrates the Natural History of Coronary Atherosclerosis

ObjectivesThis study sought to identify distinct patient groups and their association with outcome based on the patient similarity network using quantitative coronary plaque characteristics from coronary computed tomography angiography (CTA).BackgroundCoronary CTA can noninvasively assess coronary plaques quantitatively.MethodsPatients who underwent 2 coronary CTAs at a minimum of 24 months’ interval were analyzed (n = 1,264). A similarity Mapper network of patients was built by topological data analysis (TDA) based on the whole-heart quantitative coronary plaque analysis on coronary CTA to identify distinct patient groups and their association with outcome.ResultsThree distinct patient groups were identified by TDA, and the patient similarity network by TDA showed a closed loop, demonstrating a continuous trend of coronary plaque progression. Group A had the least coronary plaque amount (median 12.4 mm³ [interquartile range (IQR): 0.0 to 39.6 mm³]) in the entire coronary tree. Group B had a moderate coronary plaque amount (31.7 mm³ [IQR: 0.0 to 127.4 mm³]) with relative enrichment of fibrofatty and necrotic core (32.6% [IQR: 16.7% to 46.2%] and 2.7% [IQR: 0.1% to 6.9%] of the total plaque, respectively) components. Group C had the largest coronary plaque amount (187.0 mm³ [IQR: 96.7 to 306.4 mm³]) and was enriched for dense calcium component (46.8% [IQR: 32.0% to 63.7%] of the total plaque). At follow-up, total plaque volume, fibrous, and dense calcium volumes increased in all groups, but the proportion of fibrofatty component decreased in groups B and C, whereas the necrotic core portion decreased in only group B (all p < 0.05). Group B showed a higher acute coronary syndrome incidence than other groups (0.3% vs. 2.6% vs. 0.6%; p = 0.009) but both group B and C had a higher revascularization incidence than group A (3.1% vs. 15.5% vs. 17.8%; p < 0.001). Incorporating group information from TDA demonstrated increase of model fitness for predicting acute coronary syndrome or revascularization compared with that incorporating clinical risk factors, percentage diameter stenosis, and high-risk plaque features.ConclusionsThe TDA of quantitative whole-heart coronary plaque characteristics on coronary CTA identified distinct patient groups with different plaque dynamics and clinical outcomes. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411)     

Association between asymptomatic carotid atherosclerosis and degenerative aortic stenosis

ObjectiveDegenerative aortic stenosis shows similarities with atherosclerosis. To confirm the hypothesis that aortic stenosis is an “atherosclerosis-like” disease, we investigated the association between degenerative aortic stenosis and atherosclerosis of carotid arteries.MethodsWe studied 270 consecutive patients, 135 with degenerative aortic stenosis (trans-aortic peak velocity ≥ 2 m/sec) and other 135 subjects without aortic valve disease. All patients underwent echocardiography and ultrasound scan of the supra-aortic trunks to assess the presence of plaque and/or intima-media thickening (IMT).ResultsAtherosclerosis of carotid arteries (IMT and plaque) was significantly more frequent in patients with aortic stenosis than in controls (95.5% vs. 66.6%, p < 0.0001). The same result was confirmed as concerns carotid plaques (69.6% vs. 42.2%, p < 0.0001). In addition, there was a significant association between aortic stenosis and degenerative carotid plaque (OR = 3.13; 95% C.I. = 1.90–5.17). Thus the presence of a linear correlation between the trans-aortic peak velocity of the cases and the thickness of the plaques and IMT was evaluated by calculating the coefficient of correlation (R = 0.15 for plaque and R = 0.53 for IMT).ConclusionsThe presence of carotid atherosclerosis is associated with degenerative aortic stenosis and the severity of aortic stenosis corresponds to an increase of the thickness of plaque and IMT. This relationship is quite new.Our result strengthens the pathogenetic hypothesis “atherosclerosis-like” of degenerative aortic stenosis and suggest the ultrasound scan as a non invasive method for risk stratification in patient with aortic stenosis, with therapeutic implications especially for higher risk subgroups.     

Metabolic syndrome and coronary heart disease among Spanish male workers: a case-control study of MESYAS

Background and aimsIn Spain, the incidence of coronary heart disease is below that expected based on the burden of classic cardiovascular risk factors present in the population. Whether the risk associated with metabolic syndrome is lower in Spain deserves to be investigated. This study evaluates the association of incident clinical coronary heart disease with metabolic syndrome and each of its individual defining components in a sample of Spanish working males.Methods and resultsAmong the workers of a factory (MESYAS registry), 208 incident cases of coronary heart disease (between 1981 and 2005) were age-matched with 2080 healthy workers visited in 2004–2005. Metabolic syndrome was characterized using modified criteria of the joint consensus definition (2009). Metabolic syndrome was strongly associated with coronary heart disease (OR = 4.03; 95% CI: 2.98, 5.45) and the risk seemed to be fully explained by metabolic syndrome components (OR = 0.84, p = 0.54 after adjustment). Odds ratios for the independent effects of the diagnostic criteria were: hypertriglyceridemia (OR = 3.39, p < 0.001), hyperglycemia (OR = 2.70, p < 0.001), low HDL cholesterol (OR = 2.35, p < 0.001), hypertension (OR = 1.49, p = 0.016) and overweight (OR = 1.07, p = 0.678). Young workers showed a higher risk associated with metabolic syndrome.ConclusionThe risk associated with metabolic syndrome is fully explained by its components considered independently. The risk of coronary heart disease in a Spanish male working population is considerably increased among those with metabolic syndrome, by a factor similar to that described for other countries. Public health measures to prevent a rise in the prevalence of metabolic syndrome are advisable to minimize cardiovascular disease rate in Spain.     

Vascular reactivity in patients with undifferentiated connective tissue diseases

Assessment of changes in plaque volume is increasingly used as a surrogate-endpoint in clinical trials testing the efficacy of anti-atherosclerotic interventions. Multi-detector computed tomography (MDCT) can detect and quantify non-calcified atherosclerotic plaques, but its ability to monitor changes in plaque volume has not yet been tested.We sought to test the ability of MDCT to detect and quantify serial changes in atheroma burden in comparison with magnetic resonance imaging (MRI).MethodsRabbits (n = 12) with experimentally induced abdominal atherosclerosis were randomized to receive a plaque-regressing agent (recombinant apoA-I_Milano, n = 8) or placebo (n = 4). All animals underwent two 64-slice MDCT angiography and MRI studies (pre- and post-treatment). The primary endpoint was the change in plaque burden (defined as vessel wall volume in the 5 cm distal to the left renal artery) between pre- and post-treatment MDCT in comparison with MRI.ResultsMDCT detected a significant decrease in plaque burden caused by recombinant apoA-I_Milano (464 [423–535] to 405 [363–435] mm³, p = 0.03) that was confirmed by MRI (324 [286–412] to 298 [282–399] mm³, p = 0.03). No significant effect was noted in the placebo group either by MDCT or MRI. There were strong correlations between both modalities for the quantification of plaque burden (r = 0.750, p < 0.001) and change in plaque burden (r = 0.657, p = 0.020). MDCT overestimated plaque burden compared to MRI.On MDCT, the mean interobserver variability for plaque burden was 2.5 ± 0.4%.ConclusionsIn an animal model of atherosclerosis, MDCT accurately documented serial changes in aortic plaque burden, demonstrating good correlation and agreement with MRI-derived measurements and low interobserver variability.     

Size of emptied plaque cavity following spontaneous rupture is related to coronary dimensions, not to the degree of lumen narrowing. A study with intravascular ultrasound in vivo

OBJECTIVE—To identify any potential relations between the size of an emptied plaque cavity and the remodelling pattern, plaque or vessel dimensions, lumen narrowing, and other ultrasonic lesion characteristics.
DESIGN—Intravascular ultrasound was used to examine prospectively 51 ruptured ulcerated coronary plaques. Cross sectional area measurements comprised lumen, vessel, plaque, and emptied plaque cavity. Lumen narrowing was calculated as 1 − (lesion lumen area/reference lumen area) × 100%. A remodelling index was calculated as lesion vessel area/reference vessel area, and plaques were divided into those with values > 1.05 (group A) and  1.05 (group B).
RESULTS—Of the total of 51 plaques, 36 (71%) were assigned to group A and 15 (29%) to group B. In neither group was there a significant difference in reference dimensions and lumen narrowing. However, lesion vessel (mean (SD): 22.6 (8.1) mm² v 17.5 (4.3) mm²; p = 0.006) and plaque areas (15.8 (6.2) mm² v 12.8 (3.2) mm²; p = 0.03) were greater in group A than in group B. The cavity inside the plaque was larger in group A than in group B (2.8 (1.6) mm² v 1.8 (0.9) mm²; p = 0.007) and showed a positive linear relation with lesion and reference vessel size (r = 0.58 and 0.56, respectively; p < 0.001), but not with lumen narrowing.
CONCLUSIONS—The size of the emptied cavity inside ruptured plaques is on average larger in lesions with adaptive vascular remodelling, and shows a linear relation with lesion plaque and vessel size and with the reference dimensions, but not with the degree of lumen narrowing.


Keywords: intravascular ultrasound; ultrasonic scanning; plaque rupture; remodelling     

Coronary microvascular dysfunction is associated with higher frequency of thin-cap fibroatheroma

ObjectiveBoth coronary microvascular dysfunction and epicardial plaque vulnerability have been associated with adverse cardiovascular outcomes. However, whether microvascular dysfunction is a predictor of plaque vulnerability is not known. We hypothesized that microvascular dysfunction is associated with greater systemic inflammation and is a predictor of virtual histology–intravascular ultrasound (VH–IVUS)-defined coronary thin-cap fibroatheromas.MethodsInvasive physiologic assessment and VH–IVUS were performed and serum high-sensitivity C-reactive protein (hs-CRP) was measured in 51 patients with non-obstructive CAD [fractional flow reserve (FFR) ≥ 0.75]. Microvascular dysfunction was defined as coronary flow velocity reserve (CFVR) < 2.0. Lumen area and plaque burden and composition were assessed in each VH–IVUS frame. Frequency of thin-cap fibroatheroma (TCFA) in each artery was defined as the percentage of VH–IVUS frames with plaque burden ≥ 40% and confluent necrotic core ≥ 10% in contact with lumen for at least 3 consecutive frames.ResultsMean age was 57 ± 12 years and 25% of patients presented with acute coronary syndrome. Despite similar amount of epicardial disease, characterized by lumen area (8.9 ± 3.0 vs. 10.1 ± 3.3 mm², p = 0.3) and FFR (0.90 ± 0.08 vs. 0.92 ± 0.07, p = 0.2), patients with microvascular dysfunction had greater hs-CRP (4.2 [2.3, 7.6] vs. 1.0 [0.4, 4.2] ng/ml, p = 0.006), greater plaque burden (47 ± 10 vs. 36 ± 13%, p = 0.004), and higher frequency of TCFA (17 ± 25 vs. 6 ± 9%, p = 0.02). After adjustment for cardiovascular risk factors, hs-CRP, and plaque burden, coronary microvascular dysfunction was an independent predictor of frequency of TCFA (β = +0.42, p = 0.033).ConclusionIn patients with non-obstructive CAD, coronary microvascular dysfunction is associated with higher serum hs-CRP and is an independent predictor of more TCFAs, a marker for increased epicardial plaque vulnerability.     

Radiomics-Based Precision Phenotyping Identifies Unstable Coronary Plaques From Computed Tomography Angiography

ObjectivesThe aim of this study was to precisely phenotype culprit and nonculprit lesions in myocardial infarction (MI) and lesions in stable coronary artery disease (CAD) using coronary computed tomography angiography (CTA)-based radiomic analysis.BackgroundIt remains debated whether any single coronary atherosclerotic plaque within the vulnerable patient exhibits unique morphology conferring an increased risk of clinical events.MethodsA total of 60 patients with acute MI prospectively underwent coronary CTA before invasive angiography and were matched to 60 patients with stable CAD. For all coronary lesions, high-risk plaque (HRP) characteristics were qualitatively assessed, followed by semiautomated plaque quantification and extraction of 1,103 radiomic features. Machine learning models were built to examine the additive value of radiomic features for discriminating culprit lesions over and above HRP and plaque volumes.ResultsCulprit lesions had higher mean volumes of noncalcified plaque (NCP) and low-density noncalcified plaque (LDNCP) compared with the highest-grade stenosis nonculprits and highest-grade stenosis stable CAD lesions (NCP: 138.1 mm³ vs 110.7 mm³ vs 102.7 mm³; LDNCP: 14.2 mm³ vs 9.8 mm³ vs 8.4 mm³; both P_trend < 0.01). In multivariable linear regression adjusted for NCP and LDNCP volumes, 14.9% (164 of 1,103) of radiomic features were associated with culprits and 9.7% (107 of 1,103) were associated with the highest-grade stenosis nonculprits (critical P < 0.0007) when compared with highest-grade stenosis stable CAD lesions as reference. Hierarchical clustering of significant radiomic features identified 9 unique data clusters (latent phenotypes): 5 contained radiomic features specific to culprits, 1 contained features specific to highest-grade stenosis nonculprits, and 3 contained features associated with either lesion type. Radiomic features provided incremental value for discriminating culprit lesions when added to a machine learning model containing HRP and plaque volumes (area under the receiver-operating characteristic curve 0.86 vs 0.76; P = 0.004).ConclusionsCulprit lesions and highest-grade stenosis nonculprit lesions in MI have distinct radiomic signatures compared with lesions in stable CAD. Within the vulnerable patient may exist individual vulnerable plaques identifiable by coronary CTA-based precision phenotyping.     

CRP and CD14 polymorphisms correlate with coronary plaque volume in patients with coronary artery disease--IVUS substudy of the ENCORE trials

BackgroundSeveral proinflammatory single-nucleotide polymorphisms (SNPs) have been linked to the progression of atherosclerosis and coronary artery disease (CAD). Plaque size and its destabilization by inflammatory processes are major determinants of ischemia and acute coronary syndromes. Intravascular ultrasound (IVUS) allows for quantification of plaque size in vivo. We therefore investigated the relation of plaque size with mutations of proinflammatory genes in patients with CAD.MethodsIn 196 patients with stable CAD enrolled in the ENCORE trials coronary plaque and vessel volume was assessed by IVUS. 173 patients were successfully genotyped for polymorphisms of proinflammatory genes CD14 C(?260)T and CRP C(+1444)T using the single-nucleotide polymorphism polymerase chain reaction (SNP PCR) approach.ResultsBaseline characteristics were comparable for all genotype groups. Higher ratios of plaque volume/vessel volume were observed in patients with the CRP 1444TT (n = 11) and CD14 260TT (n = 33) genotypes (p = 0.016 and p = 0.026, respectively).ConclusionIn patients with stable coronary artery disease the CRP 1444TT and CD14 260TT variants are associated with larger coronary plaque volume independently of concomitant cardiovascular risk factors.     

Plaque characteristics and arterial remodeling in coronary and peripheral arterial systems

BackgroundFew studies have examined plaque characteristics among multiple arterial beds in vivo. The purpose of this study was to compare the plaque morphology and arterial remodeling between coronary and peripheral arteries using gray-scale and radiofrequency intravascular ultrasound (IVUS) at clinical presentation.Methods and resultsIVUS imaging was performed in 68 patients with coronary and 93 with peripheral artery lesions (29 carotid, 50 renal, and 14 iliac arteries). Plaques were classified as fibroatheroma (VH-FA) (further subclassified as thin-capped [VH-TCFA] and thick-capped [VH-ThCFA]), fibrocalcific plaque (VH-FC) and pathological intimal thickening (VH-PIT). Plaque rupture (13% of coronary, 7% of carotid, 6% of renal, and 7% of iliac arteries; P = NS) and VH-TCFA (37% of coronary, 24% of carotid, 16% of renal, and 7% of iliac arteries; P = 0.02) were observed in all arteries. Compared with coronary arteries, VH-FA was less frequently observed in renal (P < 0.001) and iliac arteries (P < 0.006). Lesions with positive remodeling demonstrated more characteristics of VH-FA in coronary (84% vs. 25%, P < 0.001), carotid (72% vs. 20%, P = 0.001), and renal arteries (42% vs. 4%, P = 0.001) compared with those with intermediate/negative remodeling. There was positive relationship between remodeling index and percent necrotic area in all four arteries.ConclusionsAtherosclerotic plaque phenotypes were heterogeneous among four different arteries; renal and iliac arteries had more stable phenotypes compared with coronary artery. In contrast, the associations of remodeling pattern with plaque phenotype and composition were similar among the various arterial beds.     

Diagnostic Accuracy of 320-Row Computed Tomography for Characterizing Coronary Atherosclerotic Plaques: Comparison with Intravascular Optical Coherence Tomography

Background/purposeThis study sought to determine the diagnostic accuracy of 320-row computed tomography (320CT) for characterizing coronary atherosclerotic plaques in comparison with optical coherence tomography (OCT).Methods/materialsFrom 32 patients, 42 coronary segments were evaluated and co-registered by both 320CT and OCT. 320CT vulnerable plaque characteristics included low attenuation plaque (LAP) (<30HU), napkin-ring sign (NRS), positive remodeling (PR) and spotty calcification (SC). The presence of macrophage, neovascularization and cholesterol crystals was also determined by OCT.ResultsMinimal lumen area was 2.78 ± 1.23 mm by OCT and 3.29 ± 1.49 mm by 320CT (p < 0.001). Noncalcified plaques were classified accordingly by both methods in 88.2% of the cases (p = 0.005). There was no association between any 320CT plaque type and OCT fibroatheroma (p = 0.62). The combination of 2 or more of the 320CT vulnerable plaque characteristics was associated with the presence of macrophage (74.2 vs. 25.8%; p = 0.034) and cholesterol crystals (85.7 vs. 14.3%; p = 0.04), but not with neovascularization (p = 0.65). The presence of all four characteristics demonstrated an accuracy of 75.1% for detecting OCT fibroatheroma.Conclusions320CT is useful for non-invasive evaluation of calcified and noncalcified tissue characteristics of coronary atheroma. The combination of all four 320CT vulnerable plaque characteristics provided the highest accuracy for detecting fibroatheromas.Summary320CT is useful for non-invasive evaluation of calcified and noncalcified tissue characteristics of coronary atheroma. The combination of all 320CT vulnerable plaque characteristics (low attenuation plaque (<30HU), napkin-ring sign, positive remodeling and spotty calcification) provided the highest accuracy for detecting fibroatheromas compared to optical coherence tomography.     

Association of virtual histology characteristics of the culprit plaque with post-fibrinolysis flow restoration in ST-elevation myocardial infarction

Objectives

We sought to test the hypothesis that virtual histology characteristics of the culprit lesion in patients with ST-elevation myocardial infarction are associated with blood flow restoration after thrombolysis.

Methods

Consecutive patients referred for coronary angiography after successful thrombolysis were included in this correlational cross-sectional study. Evaluation with intravascular ultrasound (IVUS) and virtual histology of the culprit arterial segment was performed in all cases.

Results

Forty-eight patients (60.5 ± 10.7 years) were included. TIMI flow grade 3 was found in 24 (50%). Diabetes was strongly associated with lower TIMI flow 3 rate (26.7% vs 60.6%; p = 0.029) and there was a significant difference in the time to thrombolysis (2.0 ± 0.8 hours in those with TIMI flow 3 vs 3.0 ± 0.7 hours in TIMI flow grades 1–2; p < 0.001). Patients with TIMI flow grades 3 and 1–2 had similar absolute total plaque volume (152.8 ± 59.3 mm³ vs 147.5 ± 92.3 mm³; p = 0.817) and absolute necrotic core (NC) volume (31.2 ± 13.9 mm³ vs 33.6 ± 23.2 mm³; p = 0.671). However, there were significant differences in the relative NC content, both in proportion to the whole plaque volume (26.3% vs 29.9%; p = 0.016) and as an area fraction at the largest NC site (31.5% vs 40.3%; p < 0.001).

Conclusion

The NC content of atherosclerotic plaques is meaningful for flow restoration after the occurrence of a coronary event. This finding highlights the importance of plaque composition, as studied with virtual histology, not only for the sequence of processes leading to an acute plaque-related event, but also for thrombus formation and lysis, following the occurrence of such an event.     

Combination of plaque burden,wall shear stress,and plaque phenotype has incremental value for prediction of coronary atherosclerotic plaque progression and vulnerability

Aims

Large plaque burden, certain phenotypes, and low wall shear stress (WSS) are associated with adverse outcomes and high WSS with development of plaque vulnerability. We aimed to investigate the incremental value of the combination of plaque burden, WSS and plaque phenotype for prediction of coronary atherosclerotic plaque progression and vulnerability.

Methods

Twenty patients with CAD underwent baseline and 6-month follow-up coronary virtual histology-intravascular ultrasound (VH-IVUS) and computational fluid dynamics modeling for calculation of WSS. Low WSS was defined as <10 dynes/cm² and high WSS as ≥25 dynes/cm². Baseline plaque characteristics and WSS were related to plaque progression and vulnerability.

Results

In 2249 VH-IVUS frames analyzed, coronary segments with both plaque burden >40% and low WSS had significantly greater change in plaque area at follow-up (+0.68 ± 1.05 mm²), compared to segments with plaque burden >40% without low WSS (−0.28 ± 1.32 mm²) or segments with low WSS and plaque burden ≤40% (+0.05 ± 0.71 mm²) (p = 0.047). Among plaque phenotypes, pathologic intimal thickening (PIT) had the greatest increase in necrotic core (NC) area (p = 0.06) and greatest decrease in fibro-fatty (FF) area (p < 0.0001). At follow-up, compared to segments with either plaque burden >60%, PIT, or high WSS, those with a combination of plaque burden >60%, PIT, and high WSS developed greater increase in NC area (p = 0.002), greater decrease in FF (p = 0.004) and fibrous areas (p < 0.0001), and higher frequency of expansive remodeling (p = 0.019).

Conclusion

Combination of plaque burden, WSS, and plaque phenotype has incremental value for prediction of coronary plaque progression and increased plaque vulnerability in patients with non-obstructive CAD.     

Effect of statin treatment on coronary plaque progression – A serial coronary CT angiography study

Objectives

Statins have been shown to reduce plaque progression using data on intravascular ultrasound, carotid intima-media thickness and coronary artery calcium scans. However, there is little data on effects of statins on plaque progression using Coronary CTA. The objective is to evaluate the effect of statin therapy on plaque progression using serial Coronary CTA (CCTA).

Methods

The study included 100 consecutive patients who underwent serial Coronary CTA (mean follow up: 406 ± 92 days) for evaluation of CAD without known prior heart disease or revascularization. We performed volumetric assessment of low attenuation plaque (LAP < 30 Hounsfield units), non-calcified (NCP) and calcified plaque volumes at baseline and follow up scans for vessels >2 mm in diameter. Patients who received statins were compared to those that did not.

Results

Total plaque progression was significantly reduced among statin user compared to non-statin users (−33.3 mm³ ± 90.5 vs. 31.0 mm³ ± 84.5, p = 0.0006). Statin users had significantly reduced progression of NCP volume (−47.7 mm³ ± 71.9 vs. 13.8 mm³ ± 76.6, p < 0.001) and significantly reduced progression of LAP volume (−12.2 mm³ ± 19.2 vs. 5.9 mm³ ± 23.1, p < 0.0001). When we compared for remodeling index, no statistical difference was found between the two groups (p = 0.25) and a non-significant trend toward calcium progression (29.3 mm³ ± 67.9 vs. 10.0 mm³ ± 53.2, p = 0.133). After adjustment for cardiovascular risk factors, mean plaque volume difference between statin and non-statin users was statistically significant for both LAP and NCP volumes (−18.1, 95% CI: −26.4, −9.8 for LAP; −101.7, 95% CI: −162.1, −41.4 for NCP; p < 0.001) respectively.

Conclusion

Statin therapy resulted in significantly lower progression of LAP and NCP plaques compared to non-statin users.     

Cardiac Computed Tomography Angiography Follow-Up of Resorbable Magnesium Scaffolds

IntroductionAn ancillary advantage of bioresorbable scaffolds is the possibility of non-invasive imaging assessment of the treated coronary segment. Cardiac computed tomography angiography (CCTA) studies of resorbable magnesium scaffolds (RMS) are scarce.MethodsIn this collaborative, international study, nine patients who had an RMS implanted underwent CCTA as part of follow-up assessment. Core-lab blinded quantitative and qualitative assessment was performed by an independent CCTA investigator.ResultsEight studies were amenable for quantitative analysis, and the blinded CT investigator successfully located and evaluated patency of RMS in all cases. The CCTA follow-up in-scaffold percentage diameter stenosis and area stenosis was 22.2% (12.4–30) and 39.1% (0.23–0.50), in keeping with mild in-scaffold late loss and underlying plaque growth. Moreover, a detailed coronary plaque characterization at treated segments was feasible (fibrous plaque in 69.9%, fibrofatty in 17.13%, necrotic in 4.78% and calcium in 5.72%). As in 6 out of 8 cases, the presentation was an acute coronary syndrome, these preliminary results could suggest plaque stabilization and a good coronary vessel healing with RMS.ConclusionNon-invasive, follow-up assessment of RMS with CCTA is feasible. Further CCTA studies for either clinical or research purposes with the present and upcoming generation of resorbable magnesium scaffolds are warranted.     

Impacts of age on coronary atherosclerosis and vascular response to statin therapy

Age is a well-established risk factor for cardiovascular disease. Recent trials using intravascular ultrasound (IVUS) have shown that lipid-lowering therapy with statins halts the progression or induces the regression of coronary artery plaques. However, impacts of age on coronary atherosclerosis and vascular response to statin therapy have not been fully evaluated. The effects of 8-month statin therapy on coronary atherosclerosis were evaluated using virtual histology-IVUS. IVUS data were analyzed from 119 patients who were divided into two groups according to age: elderly patients (≥65 years, n = 72) and non-elderly patients (<65 years, n = 47). No patients were taking statins or other lipid-lowering therapies at baseline. At baseline, external elastic membrane (EEM) volume (17.27 vs. 14.95 mm³/mm, p = 0.02) and plaque volume (9.49 vs. 8.11 mm³/mm, p = 0.03) in the elderly patients were significantly greater than in the non-elderly patients. The EEM volume (?2.4 %, p = 0.007) and plaque volume (?3.1 %, p = 0.007) after 8-month of statin therapy had significantly decreased in the non-elderly patients but not in the elderly patients. A significant positive correlation was observed between age and percentage change in plaque volume (r = 0.265, p = 0.004). A multivariate regression analysis showed that age was a significant predictor of the percentage change in plaque volume during statin therapy (β = 0.223, p = 0.02). Coronary atherosclerosis was more advanced and vascular responses to statin therapy were attenuated in the elderly patients compared to the non-elderly patients.     

Factor Seven Activating Protease (FSAP) expression in human monocytes and accumulation in unstable coronary atherosclerotic plaques

ObjectiveThe Factor Seven Activating Protease (FSAP) is known to influence fibrinolysis and to play a critical role in the inhibition of vascular smooth muscle cell (VSMC) proliferation and migration as well as neointima formation. In order to define the role of FSAP in vascular pathophysiology we have investigated the expression of FSAP protein and mRNA in human vascular cells and coronary atherosclerotic plaques with defined clinical features.Methods and resultsDirectional coronary atherectomy (DCA) specimens from 40 lesions were analyzed for FSAP antigen and mRNA expression. Higher level of FSAP mRNA (p < 0.001) as well as FSAP immunostaining (p < 0.005) was observed in patients with acute coronary syndromes compared to patients with stable angina pectoris. FSAP antigen was found to be focally accumulated in hypocellular and lipid-rich areas within the necrotic core of atherosclerotic plaques. FSAP was also co-localized with CD11b/CD68 expressing cells in macrophage-rich shoulder regions of the plaques. Monocyte-derived macrophages expressed FSAP in vitro and this was further induced by pro-inflammatory mediators.ConclusionsFSAP accumulation in coronary atherosclerotic lesions is due to either local synthesis by monocytes/macrophages, or uptake from the plasma due to plaque hemorrhage. The higher expression of FSAP in unstable plaques suggests that it may destabilise plaque through reducing VSMC proliferation/migration and altering the hemostatic balance.     

Plaque rupture and morphological characteristics of the culprit lesion in acute coronary syndromes without significant angiographic lesion: analysis by intravascular ultrasound

PurposeTo evaluate by intravascular ultrasound (IVUS) the characteristics of the culprit lesion with plaque rupture without significant angiographic stenosis after acute coronary syndromes (ACS).Patients and methodsAfter ACS, IVUS was performed in 68 patients (46.8 years ± 11.9) without significant angiographic stenosis (31 ± 15%). Plaque rupture was defined as a cavity within the plaque, communicating with the arterial lumen and having an overlying residual fibrous cap fragment. Qualitative analysis defined the type of plaque, and quantitative analysis evaluated plaque plus media area, plaque volume, plaque burden, and arterial remodeling index. Patients were divided into two groups: Group I with plaque rupture (25 patients) and Group II without plaque rupture (43 patients).ResultsAll patients with rupture showed soft or mixed plaque but no calcified plaque. In Group I, plaque rupture was associated with a larger plaque burden (49.8 ± 12.3% vs. 39.8 ± 12.1%, P < .0005), a more significant plaque plus media area (7.44 ± 2.9 vs. 5.24 ± 2.4 mm², P < .001), a greater plaque volume (151.9 ± 103.4 vs. 99.2 ± 81.6 mm³, P < .007), and a higher ratio of plaque volume over length (8.0 ± 3.8 vs. 5.6 ± 3.7 mm³/mm, P < .003). In Group I, positive remodeling was more frequent than intermediate remodeling (P < .03) or negative remodeling (P < .005). In Group II, there was no significant difference between the three types of remodeling.ConclusionThe plaque ruptures responsible for ACS frequently appear on voluminous plaques with a large plaque burden and positive arterial remodeling.     

Circumferential evaluation of the neointima by optical coherence tomography after ABSORB bioresorbable vascular scaffold implantation: Can the scaffold cap the plaque?

ObjectiveTo quantify the circumferential healing process at 6 and 12 months following scaffold implantation.BackgroundThe healing process following stent implantation consists of tissue growing on the top of and in the space between each strut. With the ABSORB bioresorbable vascular scaffold (BVS), the outer circumference of the scaffold is detectable by optical coherence tomography (OCT), allowing a more accurate and complete evaluation of the intra-scaffold neointima.MethodsA total of 58 patients (59 lesions), who received an ABSORB BVS 1.1 implantation and a subsequent OCT investigation at 6 (n = 28 patients/lesions) or 12 (n = 30 patients with 31 lesions) months follow-up were included in the analysis. The thickness of the neointima was calculated circumferentially in the area between the abluminal side of the scaffold and the lumen by means of an automated detection algorithm. The symmetry of the neointima thickness in each cross section was evaluated as the ratio between minimum and maximum thickness.ResultsThe neointima area was not different between 6 and 12 months follow-up (1.57 ± 0.42 mm² vs. 1.64 ± 0.77 mm²; p = 0.691). No difference was also found in the mean thickness of the neointima (median [IQR]) between the two follow-up time points (210 μm [180–260]) vs. 220 μm [150–260]; p = 0.904). However, the symmetry of the neointima thickness was higher at 12 than at 6 months follow-up (0.23 [0.13–0.28] vs. 0.16 [0.08–0.21], p = 0.019).ConclusionsA circumferential evaluation of the healing process following ABSORB implantation is feasible, showing the formation of a neointima layer, that resembles a thick fibrous cap, known for its contribution to plaque stability.     

Sex Differences in Compositional Plaque Volume Progression in Patients With Coronary Artery Disease

ObjectivesThis study sought to explore sex-based differences in total and compositional plaque volume (PV) progression.BackgroundIt is unclear whether sex has an impact on PV progression in patients with coronary artery disease (CAD).MethodsThe study analyzed a prospective multinational registry of consecutive patients with suspected CAD who underwent 2 or more clinically indicated coronary computed tomography angiography (CTA) at ≥2-year intervals. Total and compositional PV at baseline and follow-up were quantitatively analyzed and normalized using the analyzed total vessel length. Multivariate linear regression models were constructed.ResultsOf the 1,255 patients included (median coronary CTA interval 3.8 years), 543 were women and 712 were men. Women were older (62 ± 9 years of age vs. 59 ± 9 years of age; p < 0.001) and had higher total cholesterol levels (195 ± 41 mg/dl vs. 187 ± 39 mg/dl; p = 0.002). Prevalence of hypertension, diabetes, and family history of CAD were not different (all p > 0.05). At baseline, men possessed greater total PV (31.3 mm³ [interquartile range (IQR): 0 to 121.8 mm³] vs. 56.7 mm³ [IQR: 6.8 to 152.1 mm³] p = 0.005), and there was an approximately 9-year delay in women in developing total PV than in men. The prevalence of high-risk plaques was greater in men than women (31% vs. 20%; p < 0.001). In multivariate analysis, after adjusting for age, clinical risk factors, medication use, and total PV at baseline, despite similar total PV progression rates, female sex was associated with greater calcified PV progression (β = 2.83; p = 0.004) but slower noncalcified PV progression (β = –3.39; p = 0.008) and less development of high-risk plaques (β = –0.18; p = 0.049) than in men.ConclusionsThe compositional PV progression differed according to sex, suggesting that comprehensive plaque evaluation may contribute to further refining of risk stratification according to sex. (NCT02803411).