Effects of adaptive or fixed thresholds and different platforms on the assessment of plaque characteristics using coronary computed tomography angiography.

BACKGROUND: Coronary computed tomography angiography (CCTA) is used to evaluate components of atherosclerosis. Either adaptive or diverse, fixed Hounsfield Units (HU) are used to define components such as low attenuation (LAP), mixed (MP) and calcified plaque (CP). Comparisons of different platforms and different thresholding approaches have not been extensively evaluated. We compare two fixed threshold options to an adaptive threshold option within a specific platform and to fixed threshold options measured with another platform. METHODS: Coronary segments (n â€‹= â€‹24) of good image quality, with well-defined boundaries and representing a broad range of atheroma were analyzed for LAP, MP and CP. Thresholds for LAP vs MP and MP vs CP were either Fixed30/350, Fixed75/350 or based on an automatically determined Adaptive option. Pearson correlation and Bland-Altman analyses were undertaken. RESULTS: Within a single platform, measures were highly correlated irrespective of use of Adaptive or Fixed30/350 and Fixed75/350 thresholds (R â€‹≥ â€‹0.819, p â€‹< â€‹0.000001). The correlation slope for measures of LAP progressively diminished comparing the Adaptive versus Fixed30/350 and the Fixed75/350 versus the Fixed30/350 approaches but bias was small. Between-platform comparisons yielded less optimal results, particularly with respect to measures of LAP and with one platform yielding both very small LAP volumes and very small ranges of volumes. CONCLUSION: Measures of plaque components are highly correlated irrespective of use of Adaptive or Fixed threshold approaches within a given platform. But measures are more affected by the specific proprietary algorithms employed than by specific thresholding options, especially for LAP.

Recommendations for statin management in primary prevention: disparities among international risk scores.

BACKGROUND AND AIMS: Statin recommendations in primary prevention depend upon risk algorithms. Moreover, with intermediate risk, risk enhancers and de-enhancers are advocated to aid decisions. The aim of this study was to compare algorithms used in North America and Europe for the identification of patients warranting statin or consideration of risk enhancers and de-enhancers. METHODS: A simulated population (n = 7680) equal in males and females, with/without smoking, aged 45-70 years, total cholesterol 3.5-7.0 mmol/L, high-density lipoprotein cholesterol 0.6-2.2 mmol/L, and systolic blood pressure 100-170 mmHg, was evaluated. High, intermediate, and low risks were determined using the Framingham Risk Score (FRS), Pooled Cohort Equation (PCE), four versions of Systematic Coronary Risk Evaluation 2 (SCORE2), and Multi-Ethnic Study of Atherosclerosis (MESA) algorithm (0-1000 Agatston Units). RESULTS: Concordance for the three levels of risk varied from 19% to 85%. Both sexes might be considered to have low, intermediate, or high risk depending on the algorithm applied, even with the same burden of risk factors. Only SCORE2 (High Risk and Very High Risk versions) identified equal proportions of males and females with high risk. Excluding MESA, the proportion with moderate risk was 25% (SCORE2, Very High Risk Region), 32% (FRS), 39% (PCE), and 45% (SCORE2, Low Risk Region). CONCLUSION: Risk algorithms differ substantially in their estimation of risk, recommendations for statin treatment, and use of ancillary testing, even in identical patients. These results highlight the limitations of currently used risk-based approaches for addressing lipid-specific risk in primary prevention.

Atherosclerotic Coronary Plaque Regression and Risk of Adverse Cardiovascular Events: A Systematic Review and Updated Meta-Regression Analysis.

Importance: The association between changes in atherosclerotic plaque induced by lipid-lowering therapies (LLTs) and reduction in major adverse cardiovascular events (MACEs) remains controversial. Objective: To evaluate the association between coronary plaque regression assessed by intravascular ultrasound (IVUS) and MACEs. Data Sources: A comprehensive, systematic search of publications in PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science was performed. Study Selection: Clinical prospective studies of LLTs reporting change in percent atheroma volume (PAV) assessed by IVUS and describing MACE components were selected. Data Extraction and Synthesis: Reporting was performed in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The association between mean change in PAV and MACEs was analyzed by meta-regression using mixed-effects, 2-level binomial logistic regression models, unadjusted and adjusted for clinical covariates, including mean age, baseline PAV, baseline low-density lipoprotein cholesterol level, and study duration. Main Outcome and Measures: Mean PAV change and MACE in intervention and comparator arms were assessed in an updated systematic review and meta-regression analysis of IVUS trials of LLTs that also reported MACEs. Results: This meta-analysis included 23 studies published between July 2001 and July 2022, including 7407 patients and trial durations ranging from 11 to 104 weeks. Mean (SD) patient age ranged from 55.8 (9.8) to 70.2 (7.6) years, and the number of male patients from 245 of 507 (48.3%) to 24 of 26 (92.3%). Change in PAV across 46 study arms ranged from -5.6% to 3.1%. The number of MACEs ranged from 0 to 72 per study arm (17 groups [37%] reported no events, 9 [20%] reported 1-2 events, and 20 [43%] reported ≥3 events). In unadjusted analysis, a 1% decrease in mean PAV was associated with 17% reduced odds of MACEs (unadjusted OR, 0.83; 95% CI, 0.71-0.98; P = .03), and with a 14% reduction in MACEs in adjusted analysis (adjusted OR, 0.86; 95% CI, 0.75-1.00; P = .050). Further adjustment for cardiovascular risk factors showed a 19% reduced risk (adjusted OR, 0.81; 95% CI, 0.68-0.96; P = .01) per 1% decrease in PAV. A 1% reduction of PAV change between intervention and comparator arms within studies was also associated with a significant 25% reduction in MACEs (OR, 0.75; 95% CI, 0.56-1.00; P = .046). Conclusions and Relevance: In this meta-analysis, regression of atherosclerotic plaque by 1% was associated with a 25% reduction in the odds of MACEs. These findings suggest that change in PAV could be a surrogate marker for MACEs, but given the heterogeneity in the outcomes, additional data are needed.

Statin associated muscle symptoms (SAMS): strategies for prevention, assessment and management.

INTRODUCTION: Statins are the cornerstone for atherosclerotic cardiovascular disease risk reduction with recognized efficacy in primary and secondary prevention. Despite this, they remain underutilized due to concerns regarding adverse effects. Statin-associated muscle symptoms (SAMS) are the most frequent cause of medication intolerance and discontinuation with a prevalence estimated at 10%, regardless of causality, with the consequence of increased risk of adverse cardiovascular outcomes. AREAS COVERED: This clinical perspective reviews recent developments in mechanisms underlying the pathogenesis of statin myopathy, the role of the nocebo effect in perception of statin intolerance, and explores diverse components endorsed by international societies in establishing a statin intolerance syndrome. Non-statin drug alternatives that reduce low-density lipoprotein-cholesterol are also discussed, with emphasis on therapies with established effects on cardiovascular outcomes. EXPERT OPINION: Ultimately, a patient-centered clinical approach to managing SAMS is proposed to optimize statin tolerability, achieve guideline-recommended therapeutic goals and improve cardiovascular outcomes.

Measurement of Plaque Characteristics Using Coronary Computed Tomography Angiography: Achieving High Interobserver Performance.

BACKGROUND: Coronary computed tomography angiography (CCTA) is used to assess plaque characteristics, remodelling, and progression and regression. Few papers address standard operating procedures that ensure achievement of high interobserver reproducibility. Moreover, assessment of coronary artery bypass grafts has not been reported. METHODS: A training set of images was created of native coronary segments, spanning the full range of atheromatous disease from normal to severe, excluding totally occluded segments, and including segments with or without calcification (n = 24) and completely normal-appearing bypass grafts (n = 16). Three observers used a validated software program during a training phase to establish standard operating procedures and then to achieve high intraobserver performance based on Pearson's correlation coefficient. Subsequently, interobserver variability for the laboratory as a whole was determined with a focus on measures of plaque volume, low- attenuation plaque (LAP), mixed plaque (MP), and calcified plaque (CP). RESULTS: We found no substantive differences in analytical issues between grafts and native vessels and emphasize the aggregated data. The range of mean total plaque percent was approximately 55% of total vessel volume with maximal interobserver mean absolute differences of 2% or less. Percent of LAP, MP, and CP demonstrated interobserver standard errors of 1% to 2% and interobserver mean absolute differences of 0% to 1%. Pearson's correlations were all highly significant and ranged from 0.969 to 0.999. CONCLUSIONS: CCTA provides a rich diversity of measures of atherosclerosis in coronary and bypass segments that are highly reproducible with experience and adherence to standard operating procedures.

INTRODUCTION: L'angiographie cardiaque par tomodensitométrie (TDM) est utilisée pour évaluer les caractéristiques, le remodelage, la progression et la régression de la plaque. Peu d'articles portent sur les procédures opérationnelles normalisées qui permettent d'atteindre une reproductibilité inter-observateurs élevée. De plus, les greffons de pontage aorto-coronarien n'ont pas fait l'objet d'évaluation. MÉTHODOLOGIE: Un ensemble de formation composé d'images de segments d'artères coronaires natives couvrant l'ensemble de la maladie athéromateuse, c'est-à-dire de normale à sérieuse, à l'exclusion des segments totalement obstrués, mais y compris les segments calcifiés ou non (n = 24) et les greffons de pontage qui apparaissent complètement normaux (n = 16) a été créé. Trois observateurs ont utilisé un programme informatique validé durant la phase de formation pour établir des procédures opérationnelles normalisées et ensuite pour atteindre une performance intra-observateurs élevée en fonction du coefficient de corrélation de Pearson. Subséquemment, la variabilité inter-observateurs du laboratoire dans son ensemble a été déterminée plus particulièrement par les mesures du volume de la plaque, la plaque de faible atténuation (PFA), la plaque mixte (PM) et la plaque calcifiée (PC). RÉSULTATS: Nous n'avons constaté aucune différence dans les difficultés analytiques entre les greffons et les vaisseaux natifs et faisons valoir les données regroupées. La fourchette du pourcentage total moyen de la plaque était approximativement de 55 % du volume total du vaisseau avec des différences inter-observateurs absolues moyennes maximales de 2 % ou moins. Le pourcentage de la PFA, de la PM et de la PC a démontré des erreurs types inter-observateurs de 1 % à 2 % et des différences absolues moyennes inter-observateurs de 0 % à 1 %. Les corrélations de Pearson étaient toutes hautement significatives et allaient de 0,969 à 0,999. CONCLUSIONS: La TDM offre une riche diversité de mesures de l'athérosclérose dans les segments d'artères coronaires et de pontage qui, avec l'expérience et le respect des procédures opérationnelles normalisées, sont très reproductibles.

Angiographic and clinical outcomes after implantation of drug eluting stents in bifurcation lesions with crush or kissing stent technique.

BACKGROUND: Long-term outcome after bifurcation stenting with drug-eluting stents (DES) for obstructive coronary artery disease is poorly understood. In this study, we report 6-9-month angiographic follow-up and long-term clinical outcomes after implantation of drug-eluting stents by crush and kissing stent technique for coronary bifurcation lesions. METHODS: Consecutive patients undergoing bifurcation stenting with DES by crush or kissing stent technique were enrolled in a prospective registry. Angiographic follow-up was obtained at 6-9 months and clinical follow-up completed for a median of 38 months. RESULTS: A total of 86 patients participated in the study. Bifurcation stenting by crush technique was performed in 73 (85%) and by kissing stent in 13 (15%) patients. Stenting of left main bifurcation was applied in 24 (28%) patients. Angiographic follow-up was completed in 75 (87%) patients and showed restenosis in the main for 8 (11%) and side branch for 20 (27%) patients. Clinical follow-up was available for a median duration of 38 months. During follow-up, 2 (2%) patients died, 4 (5%) experienced myocardial infarction (MI), and 11 (13%) underwent target vessel revascularization (TVR) with an overall major adverse cardiac event (MACE) rate of 16%. In left main cohort, angiographic restenosis occurred in 9 (37%) patients, and 3 (12%) patients required TVR. There were no deaths or stent thrombosis. A comparison of crush and kissing stent technique showed significantly higher angiographic restenosis with crush (26% vs 13% in kissing stent patients, P = 0.046) and 95% of restenosis in crush group involved ostium of the side branch. There was no difference in clinical outcomes between the crush and kissing stent groups. Final kissing balloon dilatation (FKB) was successful in 65 (89%) patients in the crush group and associated with a significant reduction in MACE (8% in FKB successful vs 37% in FKB unsuccessful, P = 0.04) during follow-up. CONCLUSION: Bifurcation stenting with crush or kissing stent technique is safe and associated with a low rate of TLR and MACE on long-term follow-up. Crush stenting is associated with a significantly higher rate of side branch restenosis compared to kissing stent technique. FKB is associated with significant reduction in MACE during follow-up.

Clinical and angiographic outcomes with sirolimus-eluting stents in total coronary occlusions: the ACROSS/TOSCA-4 (Approaches to Chronic Occlusions With Sirolimus-Eluting Stents/Total Occlusion Study of Coronary Arteries-4) trial.

OBJECTIVES: We sought to examine angiographic and clinical outcomes with sirolimus-eluting stents (SES) in total coronary occlusion (TCO) revascularization. BACKGROUND: Despite evaluation of drug-eluting stents beyond approved indications, few studies have evaluated their clinical benefit in TCO revascularization. METHODS: Among 15 centers in North America, 200 consecutive TCO patients (78.8% >6 weeks TCO age) were enrolled for treatment with SES. The primary end point was 6-month angiographic binary restenosis within the treated segment. RESULTS: Patient characteristics included: diabetes, 24.5%; prior infarction, 33.5%; and stent length, 45.9 mm median (quartile 1, 30.2 mm; quartile 2, 62.1 mm). A total of 199 patients (99.5%) were treated with SES, and procedural success was 98.0%. The 6-month binary restenosis rates were 9.5% in-stent, 12.4% in-segment, and 22.6% in-"working length" representing the entire treatment segment. Rates of 1-year target lesion revascularization, myocardial infarction, and target vessel failure were 9.8%, 1.0%, and 10.9%, respectively. Stent thrombosis occurred in 2 patients (1.0%). Using logistic regression modeling with propensity score adjustment, the absolute reduction in binary restenosis with SES compared with a historical bare-metal stent control was 37.7% (95% confidence interval [CI]: 27.2% to 48.3%, p < 0.001; odds ratio: 0.17, 95% CI: 0.09 to 0.30, p < 0.0001). Among 32 patients (16%) identified with stent fracture, target lesion revascularization was more common than patients without fracture (25.0% vs. 6.7%, p = 0.005). CONCLUSIONS: Despite greater lesion complexity than prior TCO trials, percutaneous revascularization with SES appears safe and results in substantial reductions in angiographic restenosis and failed patency and a low rate of repeat revascularization. These findings support the use of SES in TCO revascularization. (The ACROSS/TOSCA Trial; NCT00378612).

Distribution and determinants of myocardial perfusion grade following late mechanical recanalization of occluded infarct-related arteries postmyocardial infarction: a report from the occluded artery trial.

OBJECTIVE: To evaluate the distribution and determinants of myocardial perfusion grade (MPG) following late recanalization of persistently occluded infarct-related arteries (IRA). BACKGROUND: MPG reflects microvascular integrity. It is an independent prognostic factor following myocardial infarction, but has been studied mainly in the setting of early reperfusion. The occluded artery trial (OAT) enrolled stable patients with persistently occluded IRAs beyond 24 hr and up to 28 days post-MI. METHODS: Myocardial blush was assessed using TIMI MPG grading in 261 patients with TIMI 3 epicardial flow following IRA PCI. Patients demonstrating impaired (0-1) versus preserved (2-3) MPG were compared with regard to baseline clinical and pre-PCI angiographic characteristics. RESULTS: Impaired MPG was observed in 60 of 261 patients (23%). By univariate analysis, impaired MPG was associated with failed fibrinolytic therapy, higher heart rate, lower systolic blood pressure, lower ejection fraction, LAD occlusion, absence of collaterals (P < 0.01) and ST elevation MI, lower diastolic blood pressure, and higher systolic sphericity index (P < 0.05). By multivariable analysis, higher heart rate, LAD occlusion, absence of collaterals and higher systolic sphericity index (P < 0.01), and lower systolic blood pressure (P < 0.05) were independently associated with impaired MPG. CONCLUSION: Preserved microvascular integrity was present in a high proportion of patients following late recanalization of occluded IRAs post-MI. Presence of collaterals was independently associated with preserved MPG and likely accounted for the high frequency of preserved myocardial perfusion in this clinical setting. Impaired MPG was associated with baseline clinical and angiographic features consistent with larger infarct size.

Redefining the normal angiogram using population-derived ranges for coronary size and shape: validation using intravascular ultrasound and applications in diverse patient cohorts.

OBJECTIVES: To develop a method for quantitating coronary angiographic abnormalities of segmental size and shape (tapering) in comparison to gender- and segment-specific, population derived, normal values. BACKGROUND: In the absence of obvious focal stenoses, remodeling renders the angiogram insensitive to the presence of atherosclerosis and invalidates use of a "normal reference segment" for calculation of percent diameter stenosis. METHODS: Equations were created for detection of size/shape abnormalities of coronary angiographic segments. After validation using intravascular ultrasound (IVUS), the equations were applied to a cohort of segments judged to be completely normal by a panel of highly experienced, core laboratory technicians; and a cohort of patients judged by an experienced interventionalist to have completely normal coronaries. RESULTS: In patients assessed by core technicians, 53% (162/303) of males, 39% (209/538) of normal segments in males, 60% (56/94) of females, and 40% (81/205) of normal segments in females had quantifiable abnormalities. In patients with normal coronaries as judged by an experienced interventionalist, 100% of males (n = 14) and females (n = 19), 37% (67/182) of segments in males and 43% (105/247) of segments in females had abnormalities. The left main segment was most commonly abnormal. CONCLUSIONS: We propose a set of equations validated using IVUS and based on gender- and segment-specific normal values for coronary angiographic size and shape that markedly improves the sensitivity of the coronary angiogram for detection of abnormalities. The method should replace the unfounded practice of labeling coronary angiograms as "normal" based solely on the failure to detect focal stenoses.

Validation of a new ultrasound method for the measurement of carotid artery intima medial thickness and plaque dimensions.

BACKGROUND: Carotid ultrasound is an accepted method for the detection of subclinical atherosclerosis. Valid methods that allow quantitation of carotid atheroma burden may be useful for stratifying risk. OBJECTIVE: To validate the results of intima medial thickness (IMT) and plaque measurements using a newly created software algorithm by comparing them with those obtained using a previously validated method. METHODS: Carotid ultrasound videotapes (n=24) were analyzed by experienced observers using a validated method and a new method. Ultrasound parameters were compared by measuring the difference +/- SD to yield indexes of accuracy and precision. Performance was also assessed using correlation and Bland-Altman analyses. RESULTS: Average IMT (n=24), plaque area (n=46), and several indexes that integrate IMT and plaque measurements were all found to be comparable with measurements obtained using the previously validated method. For example, the plaque area showed excellent accuracy and precision (-0.17+/-2.0 mm2, P=0.56), excellent correlation (r=0.98, standard error of the estimate = 2.01 mm2, P<0.001) and no evidence of bias using Bland-Altman analyses (Spearman's rho = 0.04, P=0.82). CONCLUSIONS: A new algorithm for the quantitation of carotid atheroma burden yields results that are comparable with those of a previously validated and widely used method. Availability of valid tools for measuring carotid ultrasound should facilitate the incorporation of this procedure into clinical risk stratification paradigms.

Validation of an automated method for assessing brachial artery endothelial dysfunction.

BACKGROUND: Endothelial dysfunction is an early finding in diverse vascular diseases and can be measured noninvasively using brachial ultrasound. There is great interest in the potential use of this parameter for assessing interventions or cardiovascular prognosis. Automated image analysis of the ultrasound images would facilitate implementation of such measurements in high throughput clinics and/or large clinical trials. OBJECTIVES: To compare a new method designed to assess brachial artery diameter and percentage diameter changes through automated, beat-by-beat image processing (Brachial Tools, Medical Imaging Applications, USA), with a nonautomated method (Prosound System, Jet Propulsion Laboratory, USA). PATIENTS AND METHODS: Brachial ultrasound tapes from 12 patients undergoing endothelial function assessment using forearm cuff-occlusion, measurement of flow-mediated dilation and responses to nitroglycerin were analyzed by both methods. RESULTS: The correlation between the two systems was excellent for both the measurement of absolute diameters (r=0.995, P<0.001) and percentage diameter changes (r=0.973, P<0.001). The automated method demonstrated no bias compared with the frame-by-frame method and excellent precision (0.07 mm and 1.62 percentage diameter change). CONCLUSIONS: The automated method provides valid data while substantially diminishing analysis time.