Clinical comparison of a handheld cardiac ultrasound device for the assessment of left ventricular function.

PURPOSE: Recently developed handheld ultrasound devices (HHUD) represent a promising method to evaluate the cardiovascular abnormalities at the point of care. However, this technology has not been rigorously evaluated. The aim of this study was to explore the correlation and the agreement between the LVEF (Left Ventricular Ejection Fraction) visually assessed by a moderately experienced sonographer using an HHUD compared to the routine LVEF assessment performed at the Echocardiography Laboratory. METHODS: This was a prospective single center study which enrolled 120 adult inpatients and outpatients referred for a comprehensive Echocardiography (EC). RESULTS: The mean age of the patients was 69.9 ± 12.5 years. There were 47 females (39.2%). The R-squared was r 0.94 (p < 0.0001) and the ICC was 0.93 (IC 95% 0.91-0.95, p ≤ 0.0001). The Bland-Altman plot showed limits of agreement (LOA): Upper LOA 10.61 and Lower LOA - 8.95. The overall agreement on the LVEF assessment when it was stratified as "normal" or "reduced" was 89.1%, with a kappa of 0.77 (p < 0.0001). When the LVEF was classified as "normal", "mildly reduced", "moderately reduced", or "severely reduced," the kappa was 0.77 (p < 0.0001). The kappa between the HHUD EC and the comprehensive EC for the detection of RWMAs in the territories supplied by the LAD, LCX and RCA was 0.85, 0.73 and 0.85, respectively. CONCLUSION: With current HHUD, an averagely experienced operator can accurately bedside visual estimate the LVEF. This may facilitate the incorporation of this technology in daily clinical practice improving the management of patients.

Optical coherence tomography assessment of acute thrombogenicity at bifurcation sites using different stenting techniques: A porcine arteriovenous shunt study.

OBJECTIVES: We aimed to compare bare-metal stents (BMS), durable-polymer everolimus-eluting stents (DP-EES), and abluminal biodegradable-polymer sirolimus-eluting stents (ABP-SES) in the bifurcation model setup. BACKGROUND: The mechanism of thrombogenicity, which differs among second-generation stents implanted using double-kissing (DK) crush or culotte stenting techniques, remains unclear. We have shown previously that setting up a porcine arteriovenous shunt model is feasible and useful to assess thrombogenicity at vessel bifurcation points. METHODS: Six porcine shunt models were prepared for the comparison between DK crush and culotte stenting techniques using BMS, DP-EES, and ABP-SES. Intracoronary imaging with high-resolution optical coherence tomography (OCT) was performed to evaluate the thrombogenicity in different stent types in the bifurcation stenting model and was evaluated by a core lab. RESULTS: Culotte stenting demonstrated more thrombogenicity at the proximal main branch (MB) with DP-EES, side branch (SB) with BMS, and the bifurcation site irrespective of the stent type, while DK crush technique exhibited thrombogenicity only at SB with BMS and ABP-SES. OCT analysis revealed malapposition of DP-EES in the proximal MB with culotte stenting. Stent expansion was generally larger in ABP-SES than BMS and DP-EES. CONCLUSIONS: The study provides hypothesis-generating findings in distinct thrombogenicity of bifurcation stenting with DP- or ABP-coated drug-eluting stents.

Angiography-derived versus invasively-determined index of microcirculatory resistance in the assessment of coronary microcirculation: A systematic review and meta-analysis.

BACKGROUND: The index of microvascular resistance (IMR) is an established tool to assess the status of coronary microcirculation. However, the need for a pressure wire and hyperemic agents have limited its routine use and have led to the development of angiography-derived pressure-wire-free methods (angiography-derived IMR [IMRAngio]). In this review and meta-analysis, we aim to assess the global diagnosis accuracy of IMRAngio versus IMR. METHODS: A systematic review of the literature was performed. Studies directly evaluating IMRAngio versus IMR were considered eligible. Pooled values of diagnostic test and summary receiver operator curve were calculated. RESULTS: Seven studies directly comparing IMRAngio versus IMR were included (687 patients; 807 vessels). Pooled sensitivity, specificity, +likelihood ratio (LR), and -LR were 82%, 83%, 4.5, and 0.26 respectively. Pooled accuracy was 83% while pooled positive predictive value and negative predictive value were 76% and 85%, respectively. Comparable results were obtained when analyzing by clinical scenario (acute and nonacute coronary syndromes). CONCLUSION: IMRAngio shows a good diagnostic performance for the prediction of abnormal IMR.

Left ventricular global longitudinal strain assessment in patients with takotsubo cardiomyopathy: a call for an echocardiography-based classification.

BACKGROUND: Takotsubo cardiomyopathy (TTC) is classified into 4 types depending on the anatomical area affected identified on gross visual assessment. We have sought to understand if it is feasible and advantageous to use left ventricular global longitudinal strain (LVGLS), LV segmental longitudinal strain and right ventricle free wall strain (RVFWS) to classify TTC. METHODS: We conducted a retrospective observational study on twenty-five patients who meet the Modified Mayo Clinic Criteria for TTC [1]. Two independent reviewers performed strain analysis, they were both blinded to patient's diagnosed classification and outcomes. RESULTS: Based on classification by traditional assessment the 92% (N.=23) were diagnosed with typical TTC, indicating apical involvement. The entire LV was affected, 67% (N.=16) had abnormal strain (STE>-18) in all three LV regions (base, mid-ventricle and apex). Seventy-one percent of patients (N.=17) had abnormal LVGLS (>-18). Abnormal strain across all three LV regions was associated with higher prevalence (70%, N.=8 Vs 30%, N.=4, respectively) of composite cardiovascular events and longer length of hospital stay. There was a statistically significant difference in average length of hospital stay in those patients who had abnormal strain in all three regions compared to those that did not have abnormal strain across all three regions (8 days compared to 3.44 days, P=0.02). CONCLUSIONS: A new classification of TCC based on strain analysis should be developed. The traditional model is arbitrary; it fails to recognize that in most patients the entire LV is affect, it does not have prognostic significance and the most prevalent typical variant indicates apical involvement. Our study suggests that the entire LV is affected, and strain analysis has prognostic significance.

Simultaneous assessment of coronary stenosis relevance with automated computed tomography angiography and intravascular ultrasound analyses and fractional flow reserve.

OBJECTIVES: To assess the diagnostic performance of computed tomography angiography (CTA) and intravascular ultrasound (IVUS) derived minimum lumen areas (MLA) from the same lesions that correspond to an FFR ≤0.80. METHODS AND RESULTS: A total of 24 patients (33 arteries) were collected retrospectively according to the following inclusion criteria: presence of a CTA diagnostic followed by an IVUS and FFR percutaneous coronary procedures. CTA and IVUS lumen contours were automatically performed using previously validated methods.The correlation between CTA and IVUS for the MLA was r = 0.45. In terms of MLA, the mean difference between CTA and IVUS was 0.81 mm2. Of note, a much smaller CTA-derived MLA (2.10 mm2) was found to be related to significant FFR lesions compared to that of the MLA derived from IVUS (3.19 mm2). The area under the curve, accuracy, sensitivity and specificity for this CTA-derived MLA were 0.80, 0.76, 0.50 and 0.87, respectively, while these values for IVUS-derived MLA were 0.87, 0.85, 0.80 and 0.87. CONCLUSIONS: Computed tomography angiography and intravascular ultrasound-derived minimum lumen areas have moderate diagnostic efficiency, albeit slightly better for IVUS, in identifying hemodynamically severe coronary stenoses. The utility of MLA, automatically derived from either CTA or IVUS as an alternative to FFR to guide the decision to revascularize, should be tested clinically.

Human vs. machine vs. core lab for the assessment of coronary atherosclerosis with lumen and vessel contour segmentation with intravascular ultrasound.

A machine learning (ML) algorithm for automatic segmentation of intravascular ultrasound was previously validated. It has the potential to improve efficiency, accuracy and precision of coronary vessel segmentation compared to manual segmentation by interventional cardiology experts. The aim of this study is to compare the performance of human readers to the machine and against the readings from a Core Laboratory. This is a post-hoc, cross-sectional analysis of the IBIS-4 study. Forty frames were randomly selected and analyzed by 10 readers of varying expertise two separate times, 1 week apart. Their measurements of lumen, vessel, plaque areas, and plaque burden were performed in an offline software. Among humans, the intra-observer variability was not statistically significant. For the total 80 frames, inter-observer variability between human readers, the ML algorithm and Core Laboratory for lumen area, vessel area, plaque area and plaque burden were not statistically different. For lumen area, however, relative differences between the human readers and the Core Lab ranged from 0.26 to 12.61%. For vessel area, they ranged from 1.25 to 9.54%. Efficiency between the ML algorithm and the readers differed notably. Humans spent 47 min on average to complete the analyses, while the ML algorithm took on average less than 1 min. The overall lumen, vessel and plaque means analyzed by humans and the proposed ML algorithm are similar to those of the Core Lab. Machines, however, are more time efficient. It is warranted to consider use of the ML algorithm in clinical practice.

Discordance in the diagnostic assessment of vulnerable plaques between radiofrequency intravascular ultrasound versus optical coherence tomography among patients with acute myocardial infarction: insights from the IBIS-4 study.

We aimed to evaluate the diagnostic agreement between radiofrequency (RF) intravascular ultrasound (IVUS) and optical coherence tomography (OCT) for thin-cap fibroatheroma (TCFA) in non-infarct-related coronary arteries (non-IRA) in patients with ST-segment elevation myocardial infarction (STEMI). In the Integrated Biomarker Imaging Study (IBIS-4), 103 STEMI patients underwent OCT and RF-IVUS imaging of non-IRA after successful primary percutaneous coronary intervention and at 13-month follow-up. A coronary lesion was defined as a segment with ≥ 3 consecutive frames (≈1.2 mm) with plaque burden ≥ 40% as assessed by grayscale IVUS. RF-IVUS-derived TCFA was defined as a lesion with > 10% confluent necrotic core abutting to the lumen in > 10% of the circumference. OCT-TCFA was defined by a minimum cap thickness < 65 µm. The two modalities were matched based on anatomical landmarks using a dedicated matching software. Using grayscale IVUS, we identified 276 lesions at baseline (N = 146) and follow-up (N = 130). Using RF-IVUS, 208 lesions (75.4%) were classified as TCFA. Among them, OCT identified 14 (6.7%) TCFA, 60 (28.8%) thick-cap fibroatheroma (ThCFA), and 134 (64.4%) non-fibroatheroma. All OCT-TCFA (n = 14) were confirmed as RF-TCFA. The concordance rate between RF-IVUS and OCT for TCFA diagnosis was 29.7%. The reasons for discordance were: OCT-ThCFA (25.8%); OCT-fibrous plaque (34.0%); attenuation due to calcium (23.2%); attenuation due to macrophage (10.3%); no significant attenuation (6.7%). There was a notable discordance in the diagnostic assessment of TCFA between RF-IVUS and OCT. The majority of RF-derived TCFA were not categorized as fibroatheroma using OCT, while all OCT-TCFA were classified as TCFA by RF-IVUS.ClinicalTrials.gov Identifier NCT00962416.

Seattle Angina Pectoris Questionnaire and Canadian Cardiovascular Society Angina Categories in the Assessment of Total Coronary Atherosclerotic Burden.

The patient reported angina measurement with the Seattle Angina Questionnaire (SAQ) has shown to have prognostic implications and became an endpoint in clinical trials. Our objective was to study physician-reported and SAQ severity with the total coronary atherosclerotic burden as assessed by 4 angiographic scores. We prospectively analyzed data of consecutive patients scheduled for coronary angiography or percutaneous coronary intervention. The Canadian Cardiovascular Society (CCS) angina categories was used as physician-reported angina. SAQ domains were categorized as severe (0 to 24), moderate 25 to 75 and mild angina (>75). All angina assessments were done before coronary angiography. Gensini, Syntax, Friesinger, and Sullivan angiographic scores were used for total atherosclerotic burden quantification: 261 patients were included in the present analysis. The median age was 66.0 (59.0 to 71.8) years, 53.6% were male and 43.7% had diabetes. The median SYNTAX score was 6.0 (0 to 18.0). The worse the symptoms of CCS categories, the more severe was the atherosclerotic burden in all angiographic scores: SYNTAX (p = 0.01); Gensini (p <0.01); Friesinger (p = 0.02) and Sullivan (p = 0.03). Conversely, SAQ domains were not able to discriminate the severity of CAD in any of the scores. The only exception was the severe SAQ quality of life that had worse Gensini score than the mild SAQ quality of life (p = 0.04). In conclusion, CCS angina categories are related to the total atherosclerotic burden in coronary angiography, by all angiographic scores. SAQ domains should be used as a measure of patient functionality and quality of life but not as a measure of CAD severity.

From anatomy to function and then back to anatomy: invasive assessment of myocardial ischemia in the catheterization laboratory based on anatomy-derived indices of coronary physiology.

For many decades, the severity of coronary artery disease (CAD) and the indication to proceed with either percutaneous coronary intervention (PCI) or surgical revascularization has been based on anatomically derived parameters of vessel stenosis, and typically on the percentage of lumen diameter stenosis (DS%) as determined by invasive coronary angiography (CA). However, it is currently a well-accepted concept that pre-specified thresholds of DS% have a weak correlation with the ischemic and functional potential of an epicardial coronary stenosis. In this regard, the introduction of fractional-flow reserve (FFR) has represented a paradigm-shift in the understanding, diagnosis, and treatment of CAD, but the adoption of FFR into the clinical practice remains surprisingly limited and sub-standard, probably because of the inherent drawbacks of pressure-wire-based technology such as additional costs, prolonged procedural time, invasive instrumentation of the target vessel, and use of vaso-dilatory agents causing side effects for patients. For this reason, new modalities are under development or validation to derive FFR from computational fluid dynamics (CFD) applied to a three-dimensional model (3D) of the target vessel obtained from CA, intravascular imaging, or coronary computed tomography angiography. The purpose of this review was to describe the technical details of these anatomy-derived indices of coronary physiology with a special focus on summarizing their workflow, available evidence, and future perspectives about their application in the clinical practice.

Comparison of plaque distribution and wire-free functional assessment in patients with stable angina and non-ST elevation myocardial infarction: an optical coherence tomography and quantitative flow ratio study.

BACKGROUND: Data comparing plaque characteristics and wire-free physiological assessment in the target vessel in patients with stable angina versus acute coronary syndrome are sparse. Therefore, we investigated the difference in plaque distribution between stable angina and non-ST-elevation myocardial infarction (NSTEMI) and explored the relationship between target vessel vulnerability by optical coherence tomography (OCT) and wire-free functional assessment with quantitative flow ratio (QFR). METHODS: Patients with stable angina (n = 25) and NSTEMI (n = 24) were in the final prospective study cohort from the DECODE study (ClinicalTrials.gov, NCT02335086). All 5480 OCT frames in the region of interest were analyzed to study plaque morphology in the target vessel. QFR was analyzed from baseline coronary angiography before percutaneous coronary intervention. Vulnerable vessel score (VVS) was calculated from each plaque, and vessel QFR was then compared. RESULTS: Out of all frames, thin-cap fibroatheroma was common with NSTEMI compared to stable angina (10.9 versus 6.3%, P < 0.01), while fibrous plaque was more commonly seen with stable angina compared to NSTEMI (19.7 versus 14.4%, P < 0.01). Calcified plaque was similar in both clinical settings (approximately 6%). Regression analysis showed that segments with normal vessel walls were located significantly farther from the other plaque types. Longitudinal distances for plaque-type in NSTEMI were numerically greater than those for stable angina; however, the mean difference was less than 10 mm. The VVS had a significant inverse linear correlation with QFR (r = -0.34, P = 0.009). CONCLUSIONS: The plaque distribution by OCT between stable angina and NSTEMI was similar. Target vessel vulnerability was greater in patients with lower QFR value.

The IMPact on Revascularization Outcomes of intraVascular ultrasound-guided treatment of complex lesions and Economic impact (IMPROVE) trial: Study design and rationale.

Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) has been shown in clinical trials, registries, and meta-analyses to reduce recurrent major adverse cardiovascular events after PCI. However, IVUS utilization remains low. An increasing number of high-risk or complex coronary artery lesions are treated with PCI, and we hypothesize that the impact of IVUS in guiding treatment of these complex lesions will be of increased importance in reducing major adverse cardiovascular events while remaining cost-effective. The "IMPact on Revascularization Outcomes of intraVascular ultrasound-guided treatment of complex lesions and Economic impact" trial (registered on clinicaltrials.gov: NCT04221815) is a multicenter, international, clinical trial randomizing subjects to IVUS-guided versus angiography-guided PCI in a 1:1 ratio. Patients undergoing PCI involving a complex lesion are eligible for enrollment. Complex lesion is defined as involving at least 1 of the following characteristics: chronic total occlusion, in-stent restenosis, severe coronary artery calcification, long lesion (≥28 mm), or bifurcation lesion. The clinical investigation will be conducted at approximately 120 centers in North America and Europe, enrolling approximately 2,500 to 3,100 randomized subjects with an adaptive design. The primary clinical end point is the rate of target vessel failure at 12 months, defined as the composite of cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization. The co-primary imaging end point is the final post-PCI minimum stent area assessed by IVUS. The primary objective of this study is to assess the impact of IVUS guidance on the PCI treatment of complex lesions.

Comprehensive assessment of coronary computed tomography angiography by using Leaman and Leiden score in overweight and obese patients.

Coronary computed tomography angiography (CCTA) is a non-invasive modality used to assess for coronary artery disease. The CT Leaman and Leiden scores utilize coronary plaque location, composition and severity of stenosis to risk stratify patients for cardiovascular events with remarkable precision. This study compares the CCTA Leaman and Leiden score between overweight and obese populations in addition to their associated baseline characteristics. All patients who underwent CCTA within the last 1 year from a single institution were included for initial analysis. Body mass index (BMI) was used to classify patients who were overweight (25.0 to < 30 kg/m2) or obese (≥ 30 kg/m2). Patients with a BMI of < 25 kg/m2 were excluded from further analysis. Patients were divided into overweight and obese groups. CT Leaman and Leiden scores, in addition to baseline characteristics were subsequently compared between the two groups. Overall, a strong correlation between CT Leaman and Leiden scores was found (R2 = 0.9831). Patients classified as obese have more coronary lesions 0.71 ± 0.12 vs 0.31 ± 0.50 in overweight patients (p = 0.02) and tended to have a higher positive CT Leiden (5.47 ± 4.10 vs 3.90 ± 1.36, p = 0.2) and Leaman (3.45 ± 2.58 vs 2.35 ± 0.90, p = 0.1). Furthermore, obese patients with a Leiden score > 5 had significantly higher scores compared to overweight patients (10.22 ± 2.54 vs 5.87 ± 0.64, p = 0.016). Obese patients had similar average CT Leaman and Leiden scores compared to overweight individuals but were more likely to have higher CT Leiden scores > 5 which may indicate a higher risk for adverse cardiovascular outcomes.

Assessment of residual thrombus burden in patients with ST-segment elevation myocardial infarction undergoing bivalirudin versus unfractionated heparin infusion: The MATRIX (minimizing adverse hemorrhagic events by transradial access site and angioX) OCT study.

BACKGROUND: Residual stent strut thrombosis after primary percutaneous coronary intervention (PCI), negatively affects myocardial perfusion, may increase stent thrombosis risk, and it is associated with neointima hyperplasia at follow-up. OBJECTIVES: To study the effectiveness of any bivalirudin infusion versus unfractionated heparin (UFH) infusion in reducing residual stent strut thrombosis in patients with ST-elevation myocardial infarction (STEMI). METHODS: Multi-vessel STEMI patients undergoing primary PCI and requiring staged intervention were selected among those randomly allocated to two different bivalirudin infusion regimens in the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and angioX) Treatment-Duration study. Those receiving heparin only were enrolled into a registry arm. Optical coherence tomography (OCT) of the infarct-related artery was performed at the end of primary PCI and 3-5 days thereafter during a staged intervention. The primary endpoint was the change in minimum flow area (ΔMinFA) defined as (stent area + incomplete stent apposition [ISA] area) - (intraluminal defect + tissue prolapsed area) between the index and staged PCI. RESULTS: 123 patients in bivalirudin arm and 28 patients in the UFH arm were included. Mean stent area, percentage of malapposed struts, and mean percent thrombotic area were comparable after index or staged PCI. The ΔMinFA in the bivalirudin group was 0.25 versus 0.05 mm2 in the UFH group, which resulted in a between-group significant difference of 0.36 [95% CI: (0.05, 0.71); p = .02]. This was mostly related to a decrease in tissue protrusion in the bivalirudin group (p = .03). There was a trend towards more patients in the bivalirudin group who achieved a 5% difference in the percentage of OCT frames with the area >5% (p = .057). CONCLUSIONS: The administration of bivalirudin after primary PCI significantly reduces residual stent strut thrombosis when compared to UFH. This observation should be considered hypothesis-generating since the heparin-treated patients were not randomly allocated.

Feasibility of a Porcine Arteriovenous Shunt Model for Assessment of Acute Thrombogenicity in Bifurcation Stenting Technique By Optical Coherence Tomography.

BACKGROUND: Double kissing (DK) crush stenting has been reported as a superior bifurcation stenting strategy compared to culotte stenting. However, the mechanism associated with the reduction of clinical events by DK crush stenting remains unclear. We therefore investigated the thrombogenicity of DK crush stenting and culotte stenting with both bare-metal stents (BMS) and drug-eluting stents (DES) and the feasibility of a novel porcine arteriovenous shunt model. METHODS: High-resolution intracoronary imaging with optical coherence tomography (OCT) evaluated the bifurcation stenting models for thrombogenicity. RESULTS: All porcine models retained continuous circulation without blood leakage. Thrombus was macroscopically demonstrated around the bifurcation in all settings. The volume of thrombus (mm3) with BMS using DK crush/culotte and DES using DK crush/culotte were 1.38/1.19 and 0.09/0.15, respectively. Culotte stenting had more thrombus in the proximal main branch, and DK crush stenting had more at the bifurcation. Unlike DK crush stenting, culotte stenting showed malapposition in the proximal main branch and bifurcation segments. CONCLUSION: The feasibility of a porcine arteriovenous shunt model to assess thrombogenicity by OCT in bifurcation stenting technique was confirmed. OCT detected less thrombogenicity in DES when used in the bifurcation model when compared to BMS.

Serial 3-Dimensional Optical Coherence Tomography Assessment of Jailed Side-Branch by Second-Generation Drug-Eluting Absorbable Metal Scaffold (from the BIOSOLVE-II Trial).

Second-generation drug-eluting absorbable metal scaffold (DREAMS 2G) is used for treating coronary lesions. However, the natural history of the jailed side-branch (SB) after DREAMS 2G implantation remains to be elucidated. The aim of this study is to investigate the effect of scaffold struts on jailed SBs as assessed by 3-dimensional (3D) optical coherence tomography (OCT) after implantation of DREAMS 2G. We enrolled the patients who received a DREAMS 2G implantation and where OCT was performed at postprocedure and 12-month follow-up in the BIOSOLVE-II trial. The area of the ostium of jailed SBs and number of compartments divided by scaffold struts were assessed by cut-plane analysis using 3D OCT. A total of 24 patients with 61 jailed SBs were analyzed in this study. The number of compartments was significantly decreased (postprocedure; 1.98 ± 0.84 vs 12 months; 1.10 ± 0.30, p <0.001) during the 12 months. Since most of the struts disappeared, the ostium area was increased in 62% of jailed SBs at 12 months, however, not significantly different from postprocedure (postprocedure; 0.74 [0.34 to 1.46] mm2 vs 12 months; 0.78 [0.41 to 1.68] mm2, p = 0.055). The number of compartments created by scaffold struts and branching angle at postprocedure had no effect on the changes of SB ostium area. DREAMS 2G has a favorable absorption process in the jailed SBs up to 12 months and may be considered as an optional therapy for treating lesions that involve SBs.

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

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: a consensus report from the Non-adherence Academic Research Consortium (NARC).

Non-adherence has been well recognized for years to be a common issue that significantly impacts clinical outcomes and health care costs. Medication adherence is remarkably low even in the controlled environment of clinical trials where it has potentially complex major implications. Collection of non-adherence data diverge markedly among cardiovascular randomized trials and, even where collected, is rarely incorporated in the statistical analysis to test the consistency of the primary endpoint(s). The imprecision introduced by the inconsistent assessment of non-adherence in clinical trials might confound the estimate of the calculated efficacy of the study drug. Hence, clinical trials may not accurately answer the scientific question posed by regulators, who seek an accurate estimate of the true efficacy and safety of treatment, or the question posed by payers, who want a reliable estimate of the effectiveness of treatment in the marketplace after approval. The Non-adherence Academic Research Consortium is a collaboration among leading academic research organizations, representatives from the U.S. Food and Drug Administration and physician-scientists from the USA and Europe. One in-person meeting was held in Madrid, Spain, culminating in a document describing consensus recommendations for reporting, collecting, and analysing adherence endpoints across clinical trials. The adoption of these recommendations will afford robustness and consistency in the comparative safety and effectiveness evaluation of investigational drugs from early development to post-marketing approval studies. These principles may be useful for regulatory assessment, as well as for monitoring local and regional outcomes to guide quality improvement initiatives.