Luminal Diameter Stenosis Research Articles

Biomarkers for identification of high-risk coronary plaques in patients with suspected coronary artery disease

Abstract Background Patients with atherosclerotic plaques containing high-risk features have an increased likelihood of events and a worse prognosis. Whether elevated levels of biomarkers of ischemia e.g. TnI and inflammation e.g. high sensitive C-reactive protein (hsCRP) are associated with the presence of high-risk coronary atherosclerotic plaques (HRP) evaluated on coronary computed tomography angiography (CCTA) is not well described. Objectives To assess the association between 1) TnI and 2) hsCRP and quantified coronary plaque burden, luminal diameter stenosis and HRP in symptomatic patients with low/intermediate pre-test probability of obstructive coronary artery disease (CAD) referred to CCTA evaluation. Methods On enrolled patients (n=1,615), CCTA were analysed using a semiautomatic software for coronary artery plaque characterization. Patients with high (>6 ng/L) and low (<3 ng/L) TnI as well as high (>2 mg/L) and low (<1 mg/L) hsCRP were identified. Associations of high levels of TnI and hsCRP compared to low levels were investigated for the following: high plaque burden (defined as having total plaque volume above the 75th percentile on CCTA), presence of significant stenosis (defined as ≥50% luminal diameter stenosis on CCTA), and presence of HRP (defined as having a plaque with at least two risk features on CCTA). Results TnI and hsCRP were both positively correlated with total plaque burden (TnI rs=0.14, p<0.001; hsCRP rs=0.08, p<0.001). In multivariate logistic regression analyses, high TnI was when compared to low TnI associated with presence of stenosis (OR 1.43, 95% confidence interval (CI) 1.03-1.99, p=0.034), the presence of HRP (OR 1.79, 95% CI: 1.17– 2.74, p=0.008) and further the subtypes of HRP including low attenuation plaque (OR 1.93, 95% CI: 1.24–3.00, p=0.003) and positive remodelling (OR 1.51, 95% CI: 1.07–2.13, p=0.018). For high hsCRP levels, only the presence of stenosis and the HRP-subtype napkin ring sign correlated significantly. Conclusion In patients with suspected CAD TnI and hsCRP are associated with the presence of HRP features. These findings suggest that inflammatory and particularly ischemic biomarkers might improve early risk stratification and potentially also affect patient management.

Abstract 11389: Circulating Aldosterone is an Independent Risk Marker for Left Main Coronary Artery Disease

Background: Elevated plasma aldosterone concentrations reflect remodeling of the vascular wall and increased cardiovascular risk, whereas data from the left main coronary artery (LMCA) are lacking. Patients with stenosis of the LMCA present difficult challenges. Therefore, the aim of this study was to investigate the relationship between plasma aldosterone concentrations and LMCA in patients with hypertension. Methods: We recruited hypertensive patients with LMCA with assessed plasma aldosterone concentrations before disease onset from the hospital between 2018 and 2022 and set them as the case group. Simultaneously, an age- and gender-matched cohort with plasma aldosterone concentration measurements but without LMCA was selected as the control group using a ratio of 1:3. Multivariable logistic regression analysis was used to assess the relationship of plasma aldosterone concentrations with LMCA. Angiographically significant LMCA stenosis is defined as luminal diameter stenosis ≥ 50%. Results: A total of 608 hypertensive patients were identified in this study, including 152 cases and 456 controls. The mean age of the patients was 60.8 ± 17.5 years, and 389 (64.0%) were men. Compared with the control group, the case group exhibited significantly higher plasma aldosterone concentrations (15.38 versus 9.68 ng/dL, P =0.009). In logistic regression analysis, higher plasma aldosterone concentrations showed 2.73-fold higher odds (95% confidence interval [CI], 1.35-3.68, P =0.003) for the presence of LMCA, which was significant in the adjusted model (odds ratio, 2.02 [95% CI, 1.18-2.97], P =0.008). In a stratified analysis, males with coronary artery disease and women of all ages showed a relationship between the two. The link between the two was unaffected by sensitivity analysis that excluded those who were exposed to interfering substances during the measurement of plasma aldosterone concentration and those who had primary aldosteronism. Conclusions: This study indicated that higher plasma aldosterone levels were associated with an increased risk of LMCA in patients with hypertension, even in the absence of primary aldosteronism. Interventional studies are needed to elucidate the health effect of treatments to lower aldosterone levels.

Pericoronary Adipose Tissue Attenuation in Patients With Acute Coronary Syndrome Versus Stable Coronary Artery Disease.

Pericoronary adipose tissue (PCAT) attenuation has been associated with coronary inflammation and can be evaluated with coronary computed tomography angiography. The aims of this study were to compare the PCAT attenuation across precursors of culprit and nonculprit lesions of patients with acute coronary syndrome versus stable coronary artery disease (CAD). In this case-control study, patients with suspected CAD who underwent coronary computed tomography angiography were included. Patients who developed an acute coronary syndrome within 2 years after the coronary computed tomography angiography scan were identified, and patients with stable CAD (defined as any coronary plaque ≥30% luminal diameter stenosis) were 1:2 propensity score matched for age, sex, and cardiac risk factors. The mean PCAT attenuation was analyzed at lesion level and compared between precursors of culprit lesions, nonculprit lesions, and stable coronary plaques. In total, 198 patients (age 62±10 years, 65% male) were selected, including 66 patients who developed an acute coronary syndrome and 132 propensity matched patients with stable CAD. Overall, 765 coronary lesions were analyzed (culprit lesion precursors: n=66; nonculprit lesion precursors: n=207; and stable lesions: n=492). Culprit lesion precursors had larger total plaque volume, fibro-fatty plaque volume, and low-attenuation plaque volume compared to nonculprit and stable lesions. The mean PCAT attenuation was significantly higher across culprit lesion precursors compared to nonculprit and stable lesions (-63.8±9.7 Hounsfield units versus -68.8±10.6 Hounsfield units versus -69.6±10.6 Hounsfield units, respectively; P<0.001), whereas the mean PCAT attenuation around nonculprit and stable lesions was not significantly different (P=0.99). The mean PCAT attenuation is significantly increased across culprit lesion precursors in patients with acute coronary syndrome, compared to nonculprit lesions of these patients and to lesions of patients with stable CAD, which may suggest a higher intensity of inflammation. PCAT attenuation on coronary computed tomography angiography may be a novel marker to identify high-risk plaques.

An acoustic based risk score in addition to pre-test probability estimation for coronary artery disease improves risk classification in patients with suspected coronary artery disease

Abstract Background The 2021 American College of Cardiology (ACC)/American Heart Association (AHA) Guideline for Evaluation and Diagnosis of Chest Pain introduced a new pre-test probability (PTP)-table for risk stratification of patients with symptoms suggestive of coronary artery disease (CAD). The CAD-score, an acoustic-based risk score for obstructive CAD, has previously shown good rule out capability in patients with suggested CAD when added to PTP. Purpose To investigate the potential of the acoustic CAD-score to 1) reclassify patients from intermediate-high to low PTP, and 2) improve risk-stratification in patients with low PTP, when added to the 2021 AHA/ACC PTP. Methods This is a retrospective study of patients with successfully obtained CAD-score from The Danish study of Non-Invasive testing in Coronary artery Disease 1 (Dan-NICAD 1) of patients without known CAD referred for coronary computed tomography angiography with angina pectoris. Patients with suspected obstructive CAD underwent invasive angiography. CAD-score was obtained with a non-invasive acoustic device analysing heart sounds based on CAD-related turbulence. CAD-score≤20 indicated low probability of CAD. PTP was calculated from sex, age, and angina symptoms according to current AHA/ACC Guidelines. Low likelihood of CAD was defined as PTP≤15%, and intermediate-high likelihood as PTP&amp;gt;15%. Hemodynamic obstructive CAD was defined as visual luminal diameter stenosis &amp;gt;90% on angiography or FFR&amp;lt;0.80%. Results Among the 1475 included patients (52.3% women, median age 57 years IQR [50–64[), 36.4% were categorized as low likelihood of CAD (PTP≤15%), and 9.8% of patients had obstructive CAD. Compared to patients with PTP≤15%, patients with PTP&amp;gt;15%, were older, more often hypertensive (49.8% vs. 35.5%), had a higher median CAD-score (28 [22–38] vs. 16 [12–22]), and had more obstructive CAD (12.4% vs. 5.2%). CAD-score reclassified 17.6% of patients with intermediate-high likelihood to a low likelihood of CAD and decreased the post-test probability of obstructive CAD from 5.2% to 4.7%. Subgroup analyses showed reclassification was greater in men, patients with PTP ≤25%, age &amp;lt;70 years or no hypertension. In the 432 patients with PTP&amp;gt;15%, age&amp;lt;70 and no hypertension, 35.4% were reclassified to low likelihood, whereas only 2.4% of patients with PTP&amp;gt;15%, age≥70 years or hypertension were ruled out by CAD-score ≤20. In patients with low PTP≤15%, CAD-score≤20 risk-stratified 361 (67.2%) patients to very low and 176 (32.8%) to an intermediate-low likelihood of CAD, but the post-test probabilities of CAD in both subgroups were still below the cut-off of 15 (3.6% vs. 8.5%). Conclusion Adding an acoustic-based CAD-score to the AHA/ACC PTP could potentially reduce the need for further diagnostic testing by 17.6% in patients with intermediate-high likelihood of CAD and in subgroups a reduction of 35% can be achieved. Use of CAD-score in low-likelihood patients only moderately improves risk classification. Funding Acknowledgement Type of funding sources: None.

Usefulness of Coronary Artery Calcium Score to Rule Out Obstructive Coronary Artery Disease Before Transcatheter Aortic Valve Implantation

Pretranscatheter aortic valve implantation (pre-TAVI) coronary evaluation using computed tomography coronary angiography (CTA) remains suboptimal. We aimed to evaluate whether coronary artery calcium score (CAC) may rule out obstructive coronary artery disease (CAD) pre-TAVI. TAVI candidates (n=230; mean age 80 ± 8 years), 49% men, underwent preprocedural CTA and invasive coronary angiography. Obstructive CAD was defined as luminal diameter stenosis of ≥50% of left main or 3 major vessels ≥70%. Vessels with coronary stents or bypass were excluded. CAC score was calculated using the Agatston method. Receiver operating characteristic was applied to establish the CAC threshold for obstructive CAD. Multivariable analysis with adjustment for clinical covariates was applied. Net reclassification for nonobstructive disease using CAC score was calculated among nondiagnostic CT scans. Median CAC score was 1,176 (interquartile range 613 to 1,967). Receiver operating characteristic analysis showed high negative predictive value (NPV) for obstructive CAD as follows: left main CAC score 252, NPV 99%; left anterior descending CAC score 250, NPV 97%; left circumflex CAC score 297, NPV 92%; and right coronary artery CAC score 250, NPV 91%. Multivariate analysis showed the highest tertile of CAC score (≥1,670) to be an independent predictor of obstructive CAD (odds ratio 10.7, 95% confidence interval 4.6 to 25, p <0.001). Among nondiagnostic CTA, net reclassification showed reclassification of 76%, 13%, 45%, and 34% of left main, left anterior descending, left circumflex, and right coronary artery for nonobstructive CAD, respectively. In conclusion, CAC score cutoffs can be used to predict nonobstructive CAD. Implementing CAC score on pre-TAVI imaging can reduce a significant proportion of invasive coronary angiography.

Improved Outcomes of Combined Main Branch Stenting and Side Branch Drug-Coated Balloon versus Two-Stent Strategy in Patients with Left Main Bifurcation Lesions.

Background Drug-eluting stent (DES) plus drug-coated balloon (DCB) is a safe and effective treatment strategy for coronary artery bifurcation lesions, but there is no report about this strategy being used for left main (LM) bifurcation lesions. We aim to explore the efficacy and safety of DES plus DCB in the treatment of LM bifurcation lesions. Methods A total of 100 patients diagnosed with LM bifurcation lesions by coronary angiography were retrospectively enrolled at our center from January 2018 to December 2019. They received either a two-stent strategy or a main branch (MB) stenting plus side branch (SB) DCB strategy and were accordingly divided into the 2-DES group and the DES + DCB group. Patients treated with DES + DCB were compared with a cohort of matched patients treated with a 2-DES strategy. Clinical data was collected and quantitative coronary analysis was performed. Results For immediate postoperative angiography, though the two groups had no differences in the minimal luminal diameter (MLD) and luminal stenosis of MB, the DES + DCB group had significantly lower SB ostial MLD and a higher degree of residual lumen stenosis than the 2-DES group (P < 0.05). At the time of follow-up, the SB ostial MLD of the DES + DCB group was higher than that of the 2-DES group, but lumen stenosis, late lumen loss (LLL), and LLL at the distal end of the left MB were all smaller than those of the 2-DES group (Ps < 0.05). Furthermore, the incidence of lumen restenosis and MACE between the two groups had no significance. Conclusion The combination of DES and DCB is relatively safe and effective for the treatment of LM bifurcation lesions, and this strategy seems to have advantages in reducing LLL at the SB ostium.

Diagnostic Improvements of Deep Learning-Based Image Reconstruction for Assessing Calcification-Related Obstructive Coronary Artery Disease.

Objectives: The objective of this study was to explore the diagnostic value of deep learning-based image reconstruction (DLR) and hybrid iterative reconstruction (HIR) for calcification-related obstructive coronary artery disease (CAD) evaluation by using coronary CT angiography (CCTA) images and subtraction CCTA images.Methods: Forty-two consecutive patients with known or suspected coronary artery disease who underwent coronary CTA on a 320-row CT scanner and subsequent invasive coronary angiography (ICA), which was used as the reference standard, were enrolled. The DLR and HIR images were reconstructed as CTADLR and CTAHIR, and, based on which, the corresponding subtraction CCTA images were established as CTAsDLR and CTAsHIR, respectively. Qualitative images quality comparison was performed by using a Likert 4 stage score, and quantitative images quality parameters, including image noise, signal-to-noise ratio, and contrast-to-noise ratio were calculated. Diagnostic performance on the lesion level was assessed and compared among the four CCTA approaches (CTADLR, CTAHIR, CTAsDLR, and CTAsHIR).Results: There were 166 lesions of 86 vessels in 42 patients (32 men and 10 women; 62.9 ± 9.3 years) finally enrolled for analysis. The qualitative and quantitative image qualities of CTAsDLR and CTADLR were superior to those of CTAsHIR and CTAHIR, respectively. The diagnostic accuracies of CTAsDLR, CTADLR, CTAsHIR, and CTAHIR to identify calcification-related obstructive diameter stenosis were 83.73%, 69.28%, 75.30%, and 65.66%, respectively. The false-positive rates of CTAsDLR, CTADLR, CTAsHIR, and CTAHIR for luminal diameter stenosis ≥50% were 15%, 31%, 24%, and 34%, respectively. The sensitivity and the specificity to identify ≥50% luminal diameter stenosis was 90.91% and 83.23% for CTAsDLR.Conclusion: Our study showed that deep learning–based image reconstruction could improve the image quality of CCTA images and diagnostic performance for calcification-related obstructive CAD, especially when combined with subtraction technique.

Prevalence of coronary artery disease among patients with bicuspid aortic valve stenosis undergoing computed tomography before transcatheter aortic valve implantation

Abstract Introduction A lower prevalence of coronary artery disease (CAD) was previously reported among bicuspid aortic valve (BAV) patients compared with tricuspid aortic valve (TAV) patients undergoing surgical aortic valve replacement. Unknown is the prevalence of CAD among BAV patients undergoing transcatheter aortic valve implantation (TAVI). Methods Consecutive BAV patients undergoing cardiac computed tomography angiography (CCTA) before TAVI were included. Studies with insufficient imaging quality were excluded. Forty-nine patients with history of prior percutaneous coronary intervention or coronary artery bypass graft surgery were also excluded. Coronary artery stenosis was categorized as ≤50% or &amp;gt;50% luminal diameter stenosis. Results One hundred and fourteen consecutive BAV patients were enrolled (age 72±10.4 years, 64% males). BAV type 1A was the most common type (62%), followed by BAV type 0 (18%) and type 1C (10%). Cardiovascular risk factors were frequent: 23% (26) had history of diabetes mellitus, 45% (51) had dyslipidemia, 56% (64) had hypertension, and 25% (29) were current or past smokers. No correlation was found between calcium scoring of the aortic valve (3664.49±1671.01 Agatston Units) and calcium scoring of the coronary arteries (410.51±546.59 Agatston Units), correlation coefficient 0.43 (p=0.68). Obstructive coronary artery stenosis (&amp;gt;50% luminal diameter stenosis) was observed among the minority (16%) of BAV patients. A single vessel disease was found in 7% of BAV patients, two vessels disease in 5% and triple vessels disease in 4%. Three BAV patients had a single vessel chronic total occlusion. Conclusion Among patients with BAV referred for TAVI, CCTA showed a low prevalence of obstructive coronary artery disease. The absence of correlation between aortic valve and coronary artery calcium scoring suggests the possibility of two heterogeneous aspects of the complex BAV disease. Funding Acknowledgement Type of funding sources: None.

Diagnostic accuracy and reclassification potential of the acoustic CADScor algorithm in intermediate risk patients with suspected coronary artery disease

Abstract Background Validation studies of the 2019 European Society of Cardiology pre-test probability model (ESC-PTP) for coronary artery disease (CAD) report that 35–40% of patients have intermediate pre-test risk (ESC-PTP 5-&amp;lt;15%). A clear strategy for deferral or referral in this group has not been established. Stratification tools with a high negative predictive value (NPV) are especially wanted to improve pre-test risk estimates. Acoustic detections of coronary stenosis are a new technology which could potentially be useful to supplement PTP stratification. One of the devices, the CADScor®System, has been shown to down-classify &amp;gt;40% of patients to low risk without increasing CAD prevalence. However, the clinical utility of using the CADScor algorithm (version (V)3.1) has not be validated. Purpose 1) To validate the diagnostic performance of the CADScor®System (V3.1), and 2) to study the reclassification potential of a clinical likelihood strategy by ESC-PTP estimation supplemented by a CAD-score. Methods In total, 1732 patients without known CAD but with symptoms suggestive hereof underwent coronary CTA as a first-line diagnostic test. Based on an interview prior to coronary CTA, the ESC-PTP model was applied and sound recordings were performed using the acoustic CADScor® System. Patients with a suspected &amp;gt;50% diameter stenosis in any coronary segment at coronary CTA were referred to investigation with Invasive angiography (ICA) with measurement of Fractional flow reserve (FFR). The ESC-PTP risk estimation was divided according to the recommended cut-offs of &amp;lt;5%, 5-&amp;lt;15% and &amp;gt;15% PTP of obstructive CAD. Haemodynamically obstructive CAD was defined as: (1) FFR value &amp;lt;0.80, (2) luminal diameter stenosis reduction &amp;gt;90%, or (3) luminal diameter stenosis reduction ≥50% if FFR was indicated but not performed. A predefined cut-off value of 20 was used for CAD-score values to rule-out CAD. Results A suspected stenosis was found in 439 patients (26%) after coronary CTA. The follow up with ICA with FFR showed significant stenoses in 198 patients (12%). In the entire cohort using the ≤20 CAD-score cutoff for CAD rule-out, sensitivity was 85.3% (95% CI 79.5–89.9%), specificity was 40.3% (95% CI 37.8–42.9%), the PPV was 5.9% (95% CI 13.8–18.3%)), and the NPV was 95.4% (95% CI 93.4–96.9%). Hence, the disease prevalence of obstructive CAD was 4.6% in the ruled-out patients. Applying the ≤20 CAD-score cutoff for CAD rule-out in intermediate risk patients (ESC-PTP 5-&amp;lt;15%) a total of 316 patients (48%) were down-classified to low risk with an obstructive CAD prevalence of 3.5%. Conclusion Having high NPV, the CADscor holds excellent rule-out power. Interestingly, the CADscor has reclassification properties in intermediate CAD risk patients where almost 50% can be deferred form further testing without increasing obstructive CAD risk. Thus, the CADscor can supplement clinical assessment to guide decisions on the need for further testing. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The study was supported by the Health Research Fund of Central Denmark Region, Aarhus University Research foundation and by an institutional research grant from Acarix A/S, Denmark. Patient flowReclassification potential

Long-term safety and performance of a novel conical bioresorbable vascular scaffold: insights from in-vitro and in-vivo studies

Abstract Background The phenomenon of size-mismatches between cylindrical stents and tapered vessels is not uncommon in current endovascular interventions which is associated with poor clinical outcomes. Purpose The aim of the present study was to evaluate the mechanical properties of the novel conic BRS and to validate its performance with the support of optical coherence tomography (OCT), quantitative coronary angiography (QCA) and histology up to 2 years in a porcine model. Methods We produced the conical BRS with the four-axis 3D printing system, with a computer-controlled rotational axis (the 4th axis) in addition to the 3 axes of traditional 3D printing systems. Mechanical properties were evaluated by recoil and radial strength, cyclic fatigability testing. Twelve swine that received 12 conic BRS were evaluated by OCT, QCA and histology post-implantation and at 12 and 24 months. Results The in vitro study showed no fractures after accelerated cycle testing over time (at 3.8×108 cycles). The recoil rate of the scaffolds after plate compress test was 14.3±0.61%. There was no significant peri-operative complications. By OCT, 60±21 struts per BRS were recognizable by 2 years. Quantitative coronary angiography showed late luminal loss and percent diameter stenosis were 0.02±0.52 mm and 0.50±16.90% at 2-year follow-up. Histopathological analysis demonstrated mild vessel injuries, inflammatory cell infiltration around struts at 1 and 2 years follow ups. Conclusions The conical BRS showed optimal performance and has the potential to improve clinical outcome. OCT and histological images Funding Acknowledgement Type of funding source: None

Diagnostic and prognostic value of coronary artery calcium score of zero: is it time for guidelines to change?

Abstract Introduction Cardiac computed tomography (CT) use has progressively increased as the preferred initial test to rule out coronary artery disease (CAD) when clinical likelihood is low. Coronary artery calcium (CAC) detected by CT is a well-established marker for cardiovascular risk. However, it is not recommended for diagnosis of obstructive CAD. Absence of CAC, defined as an Agatston score of zero, has been associated to good prognosis despite underestimation of non-calcified plaques. Purpose To evaluate whether zero CAC score could help ruling out obstructive CAD in a safely manner. Methods Observational study based on a prospective database of patients (pts) referred to cardiac CT between 2017 and 2019. Pts with an Agatston score of zero were selected. Results We included 176 pts with zero CAC score and non-invasive coronary angiography performed. The median duration of follow-up was 23.9 months. Baseline characteristics of the population are shown in Table 1. In 117 pts (66.5%), cardiac CT was indicated as part of their chest pain evaluation. Mean age was 57.2 years old, 68.2% were women and only and 9.4% were active smokers. Normal coronary arteries were found in 173 pts (98.3%). Obstructive CAD, defined as ≥50% luminal diameter stenosis of a major vessel, was present in 1/176 (0.6%); while non-obstructive atherosclerotic plaques were found in 2 pts (1.1%). During follow-up, one patient died of out-of-hospital cardiac arrest. None either suffered from myocardial infarction or needed coronary revascularization. Conclusions In our cohort, a zero CAC score detected by cardiac CT rules out obstructive coronary artery disease in 98.3%, with only 1.7% of non-calcified atherosclerosis plaques and 0.6% of major adverse events. Although further research on this topic is needed, these results support the fact that non-invasive coronary angiography could be avoided in patients with low clinical likelihood of CAD and zero CAC score, facilitating the management of the increasing demand for coronary CT and reduction of radiation dose. Funding Acknowledgement Type of funding source: None

Gender-Related Differences in Clinical Presentation and Angiographic Findings in Patients with Ischemia and No Obstructive Coronary Artery Disease (INOCA): A Single-Center Observational Registry

Ischemia and no obstructive coronary arteries (INOCA) is a common clinical presentation, with a variety of causes that are often not fully investigated in routine clinical practice. The goal of our study was to characterize a real-world population of patients with INOCA, with a deeper focus on symptoms and stress test findings. The study population consisted of 435 patients who underwent diagnostic coronary angiography for anginal symptoms and/or evidence of myocardial ischemia at non-invasive imaging. In all patients angiography demonstrated nonobstructive coronary artery disease (CAD, less than 30% luminal diameter stenosis or fractional flow reserve > 0.8 and/or instantaneous wave-free ratio > 0.89). Fifty-four percent of the patients were women. Atypical clinical presentation was more common in women (59.5 vs. 49.5%, p = 0.037). Women were more likely to have normal coronary arteries than men (41.8 vs. 16.2%, p < 0.001), and less likely than men to have hemodynamically non-significant CAD (32.1 vs. 55.1%, p < 0.001). No significant correlation between typicality of symptoms and evidence of ischemia was found in those patients (244/435, 56.1%) who had either dobutamine stress echocardiography or electrocardiogram stress test. INOCA is a common clinical condition, prevalent in women often presenting with atypical symptoms.

Comparison of Machine Learning Computed Tomography-Based Fractional Flow Reserve and Coronary CT Angiography-Derived Plaque Characteristics with Invasive Resting Full-Cycle Ratio.

Background: The aim is to compare the machine learning-based coronary-computed tomography fractional flow reserve (CT-FFRML) and coronary-computed tomographic morphological plaque characteristics with the resting full-cycle ratio (RFRTM) as a novel invasive resting pressure-wire index for detecting hemodynamically significant coronary artery stenosis. Methods: In our single center study, patients with coronary artery disease (CAD) who had a clinically indicated coronary computed tomography angiography (cCTA) and subsequent invasive coronary angiography (ICA) with pressure wire-measurement were included. On-site prototype CT-FFRML software and on-site CT-plaque software were used to calculate the hemodynamic relevance of coronary stenosis. Results: We enrolled 33 patients (70% male, mean age 68 ± 12 years). On a per-lesion basis, the area under the receiver operating characteristic curve (AUC) of CT-FFRML (0.90) was higher than the AUCs of the morphological plaque characteristics length/minimal luminal diameter4 (LL/MLD4; 0.80), minimal luminal diameter (MLD; 0.77), remodeling index (RI; 0.76), degree of luminal diameter stenosis (0.75), and minimal luminal area (MLA; 0.75). Conclusion: CT-FFRML and morphological plaque characteristics show a significant correlation to detected hemodynamically significant coronary stenosis. Whole CT-FFRML had the best discriminatory power, using RFRTM as the reference standard.

Coronary CT angiography derived plaque markers correlated with invasive instantaneous flow reserve for detecting hemodynamically significant coronary stenoses

PurposeThe study aimed to compare morphological and anatomic plaque markers derived from coronary computed tomography angiography (cCTA) for the detection of lesion specific ischemia with invasive instantaneous wave free ratio (iFR®) as the reference standard. MethodsIn our prospective study, we enrolled patients with suspected coronary artery disease (CAD), who had undergone cCTA, using a low-dose third-generation dual-source CT and invasive coronary angiography (ICA) with iFR® measurement. Various plaque markers were assessed on cCTA. Discriminatory power of these markers for the detection of ischemia-inducing coronary artery disease was evaluated against invasive iFR®. ResultsOur study cohort included 39 patients (66.6 ± 12.0 years, 72 % male). Among 54 vessel-specific lesions, 15 lesions (28 %) were characterized as hemodynamically significant by iFR® ≤0.89. The area under the curve (AUC) of lesion length/ minimal luminal diameter4 (LL/MLD4) (0.84) was greater than the AUC of minimal luminal area (MLA) (0.82), MLD (0.81), the degree of luminal diameter stenosis (0.81), corrected coronary opacification (CCO) (0.79), remodeling index (RI) (0.75), and percentage aggregate plaque volume (%APV) (0.72). LL, vessel volume (VV), total plaque volume (TPV), calcified and non-calcified plaque volume (CPV and NCPV) did not reach statistical significance and were unable to discriminate between vessels with and without ischemia-inducing coronary stenosis. ConclusionLL/MLD4, MLA, MLD, the degree of luminal diameter stenosis, CCO, RI, and %APV derived from cCTA can support the detection of hemodynamically significant coronary stenosis as compared with iFR®, with LL/MLD4 showing the greatest discriminatory power.

P5632Different impact of lesion length on fractional flow reserve in intermediate coronary lesions between each coronary artery

Abstract Background Previous studies reported that lesion length was an important geometric parameter in addition to the degree of stenosis in the determinant of functional significance of coronary artery stenosis. Nevertheless, the optimal cutoff value of lesion length for predicting functional significance for each coronary artery has not yet been evaluated, though previous studies revealed that the cutoff value of minimum lumen diameter measured on coronary angiography (CAG) to predict fractional flow reserve (FFR) &lt;0.80 is different for each coronary artery Purpose This study evaluated whether the impact of lesion length on functional significance is similar between each coronary artery for lesions with intermediate stenosis. Methods Patients with suspected coronary artery disease who had at least one intermediate coronary lesion (luminal diameter stenosis of 70 to 80% by visual estimation on CAG) and underwent FFR measurement for the evaluation of myocardial ischemia were evaluated. Quantitative coronary angiography analysis including percent diameter stenosis and lesion length was performed. FFR was measured as the ratio of the mean distal coronary artery pressure to the mean aortic pressure during maximal hyperemia induced by intravenous infusion of adenosine triphosphate (150 μg /kg/min). The area under the receiver operating characteristics (ROC) curve was estimated for the best cutoff value as a predictor of FFR value of ≤0.80 for each coronary artery. Results A total of 221 de novo lesions that underwent FFR measurement were enrolled. The average FFR value was 0.81±0.07. Although lesion length was similar among the lesions with an FFR &gt;0.80 at different locations, the mean lesion length was significantly longer for lesions in the right coronary artery (RCA) with an FFR ≤0.80 than for those in the left anterior descending artery (LAD) and left circumflex artery (13.4±3.4 versus 8.6±3.1 versus 12.0±3.7 mm, p&lt;0.001). ROC analysis demonstrated that the optimal cutoff value of lesion length for predicting an FFR ≤0.80 was 10.0 mm in the LAD (0.56 area under the curve, 48% sensitivity, 76% specificity), whereas 13.1 mm in the RCA (0.84 area under the curve, 67% sensitivity, 93% specificity) (Figure). ROC analysis of LL for FFR≤0.80 Conclusions A longer lesion length is required to achieve FFR&lt;0.80 in the RCA than in the other arteries. This may suggest the low possibility of an FFR ≤0.80 when stenosis is focal and short in the RCA with stenosis of 70 to 80% by visual estimation on CAG.

Gender differences in thrombogenicity among patients with angina and non-obstructive coronary artery disease.

Women more often present with angina and non-obstructive coronary artery disease (ANOCA) and have poorer clinical outcomes than men. These findings may be related to sex associated differences in inflammation and thrombogenicity. Consecutive patients (n = 134) with ANOCA (luminal diameter stenosis < 50%) undergoing elective cardiac catheterization were included in post hoc analysis of Multi-Analyte, thrombogenic, and Genetic Markers of Atherosclerosis (MAGMA, NCT01276678) study. Patients with prior revascularization, coronary artery bypass grafting or myocardial infarction were excluded. Blood for thromboelastography, oxidized LDL β2-glycoprotein complex (AtherOx), oxidized-LDL, lipid profile, and urine for 11-dehydrothromboxane B2 (dTxB2) were obtained before catheterization. All women (n = 75) were post-menopausal and tended to be older than men (61.4 ± 10.6 vs. 58.6 ± 9.9year, p = 0.12), and were significantly more thrombogenic with higher thrombin-induced platelet-fibrin strength (TIP-FCS, mm) (68.0 ± 4.5 vs. 64.5 ± 6.2mm, p = 0.001), clotting index (0.35 ± 2.22 vs. - 0.72 ± 2.75, p = 0.02), K (measure of the speed to reach 20mm of clot strength from an amplitude of 2mm) (2.2 ± 1.6 vs. 1.7 ± 0.5min, p = 0.01), and fibrinogen activity (degrees) (66.6 ± 7.1 vs. 62.9 ± 7.5, p = 0.009). Markers of inflammation were not significantly different between the two groups. Women had higher total cholesterol, total LDL, LDL subtypes 1 and 2, total HDL, HDL subtypes 2 and 3, and ApoA1 (p < 0.05 for all). On multivariate regression, TIP-FCS remained significantly higher in women (p < 0.0001). Women with ANOCA are more thrombogenic than men. This fundamental difference in thrombogenicity may affect gender-related outcomes and warrants further investigation.

High-density lipoprotein cholesterol and the risk of obstructive coronary artery disease beyond low-density lipoprotein cholesterol in non-diabetic individuals.

The relationship between high-density lipoprotein cholesterol and the severity of coronary artery disease beyond low-density lipoprotein cholesterol, the primary target of cholesterol-lowering therapy, remains uncertain. We evaluated the association between high-density lipoprotein cholesterol and obstructive coronary artery disease using parameters of any obstructive plaque, obstructive plaque in the left main coronary artery or proximal left anterior descending artery, and obstructive plaque in multi-vessels, according to low-density lipoprotein cholesterol levels. We analyzed 5130 asymptomatic non-diabetics who underwent coronary computed tomography angiography for general health examination. Obstructive plaque was defined as a plaque with ≥50% luminal diameter stenosis. The participants were divided into three groups based on low-density lipoprotein cholesterol levels of ≤129, 130-159, and ≥160 mg/dl. The prevalence of any obstructive plaque (5.9% vs 6.4% vs 10.6%) and obstructive plaque in the left main coronary artery or proximal left anterior descending artery (2.1% vs 2.1% vs 4.3%) significantly increased with low-density lipoprotein cholesterol category (all p < 0.05). Compared with subjects with high-density lipoprotein cholesterol level ≥40 mg/dl, those with high-density lipoprotein cholesterol level <40 mg/dl had a significantly higher prevalence of any obstructive plaque (10.4% vs 5.1%), obstructive plaque in the left main coronary artery or proximal left anterior descending artery (3.6% vs 1.8%), and obstructive plaque in multi-vessels (4.3% vs 1.1%), only in the group with low-density lipoprotein cholesterol level ≤129 mg/dl (all p < 0.05). Multiple regression analysis showed that increased high-density lipoprotein cholesterol levels were associated with a reduced risk of all obstructive coronary artery disease parameters only in the group with low-density lipoprotein cholesterol level ≤129 mg/dl (all p < 0.05). Increased high-density lipoprotein cholesterol levels were independently associated with a lower risk of obstructive coronary artery disease in asymptomatic non-diabetics with low low-density lipoprotein cholesterol levels.

HDL3-C is a Marker of Coronary Artery Disease Severity and Inflammation in Patients on Statin Therapy.

Low high-density lipoprotein (HDL-C) and inflammation are risk factors for coronary artery disease (CAD). However, limited data are available determining the role of HDL-C sub-particles HDL2-C and HDL3-C for assessing CAD severity in patients on statin therapy. Blood samples were obtained prior to cardiac catheterization in 304 consecutive patients with suspected CAD on statin therapy in this sub-analysis of Multi-Analyte, thrombogenic, and Genetic Markers of Atherosclerosis (MAGMA, NCT01276678) study. Detailed lipid profiling and oxidized LDL (ox-LDL) were analyzed. CAD severity was angiographically defined as severe CAD (>75% luminal diameter stenosis [LDS]) and non-severe CAD (≤75% LDS). Multi-regression analysis was performed to test for statistical significance. Receiver operator curve (ROC) analysis was performed to determine cut-point for predicting severe CAD. Patients with severe CAD had a significantly lower total-HDL-C, lower HDL3-C and higher lipoprotein(a) levels. HDL3-C and lipoprotein(a) cholesterol [Lp(a)-C] retained statistical significance on multiple regression analysis. ROC analysis showed HDL3-C to have a C-statistic of 0.60 (p = 0.003) and Lp(a)-C to have a C-statistic of 0.61 (p = 0.0007). Patients with HDL3-C ≤ 33 mg/dL and Lp(a)-C > 7 mg/dL were found to have significantly elevated ox-LDL levels. In patients on statin therapy, HDL3-C and Lp(a)-C improve prediction of severe CAD compared to a traditional lipid panel. In addition, patients with HDL3-C ≤ 33 mg/dL and Lp(a)-C > 7 mg/dL have greater inflammation marked by ox-LDL. Further studies are needed to evaluate the utility of these novel biomarkers in predicting CAD severity.

OVERCOMING EXTREMELY CALCIFIED CORONARY LESIONS WITH A DEDICATED SUPER HIGH-PRESSURE BALLOON: A SINGLE HOSPITAL EXPERIENCE

A dedicated super-high pressure noncompliant balloon (OPN NC; SIS Medical AG, Winterthur, Switzerland) has been designed to optimize dilatation of rigid coronary lesion with heavy calcification. A performance of this balloon either in in-stent restenosis or native coronary disease, both in elective cases and in acute coronary syndrome, has never been studied in our hospital. From September 2016 to August 2017 in Royal Alexandra Hospital, 13 consecutive patients with extremely calcified coronary stenotic lesions in which conventional dilatation with NC balloon at rated burst pressure remained incapable of obtaining adequate lumen gain necessitating further dilatation with OPN NC balloon were retrospectively evaluated. Residual luminal diameter stenosis <30% was considered angiographic success. We measured baseline, post NC balloon and post OPN NC balloon minimal lumen diameter (MLD) as well as percentage of diameter stenosis (%DS). 12 out of 13 extremely calcified lesions were successfully dilated (92.3%). In two patients with NSTEMI, the lesions were unable to be crossed with either such OPN NC balloon or any very low-profile balloon mandating rotational atherectomy. In one of these two patients, however, OPN NC balloon was still required for stent optimization after successful lesion preparation with rotational atherectomy. One extremely calcified lesion with in-stent restenosis in previously under deployed lesion even ruptured two OPN balloons, luminal dilatation was achieved perfectly, nevertheless. This balloon was also successfully applied in the case with acute lateral wall STEMI. With OPN NC balloon acute luminal gain were greater while %DS was lower. There was no evidence of complication observed regarding coronary dissection, vessel perforation or balloon entrapment. Additionally, no MACE was revealed immediately post dilatation as well as at 30-day follow up. In detail, our study illustrated mean lesion reference diameter of 3.32 mm(+/- 0.3), mean pretreatment MLD of 0.4mm(+/-0.2), mean diameter stenosis of 87.8% (+/- 7.3), mean lumen gain post conventional NC balloon of 1.79 mm (+/- 0.42), and mean lumen gain post OPN NC balloon of 2.67mm(+/-0.44) Very high-pressure dilatation resorting OPN NC balloon should be considered as not only effective but also safe approach when experiencing extremely calcified lesions undilatable by conventional high-pressure NC balloon. This strategy helped avoid employing rotational atherectomy in most cases; however, such atherectomy device remained indispensable in extremely rigid coronary lesions.

Extent of coronary atherosclerosis and arterial remodelling in women: the NHLBI-sponsored Women's Ischemia Syndrome Evaluation.

Information regarding the pathogenesis of ischemic heart disease (IHD) in women is limited. Sex-specific responses to atherosclerosis and coronary arterial remodelling in women versus men have been hypothesized, but limited study exists. Case-matched study of 174 women with suspected ischemia referred for coronary angiography: 87 with non-obstructive coronary artery disease (CAD) (no luminal diameter stenosis >20% in any coronary artery) and 87 age and ethnicity matched women with obstructive CAD. Groups were compared with regard to atheroma burden and coronary arterial remodelling assessed by coronary artery intravascular ultrasound (IVUS). IVUS revealed more extensive atheroma with obstructive CAD vs. those without obstructive CAD, with greater percent atheroma volume (PAV) (36.1%±9.8% vs. 25.4%±9.1%, P<0.0001), total atheroma volume (TAV) (140.8±58.7 vs. 98.8±46.9 mm3, P<0.0001) and percentage of images containing plaque (70.0%±30.5% vs. 35.7%±32.6%, P<0.0001). Adjusting for risk factors, PAV (35%±1% vs. 28%±1%, P=0.0008), TAV (131±7 vs. 115±7 mm3, P=0.110) and percentage of images containing plaque (66%±4% vs. 45%±5%, P=0.0008) remained greater with obstructive CAD. Obstructive CAD was associated with smaller lumen volumes (251.9±92.8 vs. 289.7±91.8 mm3, P=0.005), but surprisingly, the external elastic membrane (EEM) volume was very similar comparing the groups (392.7±128.1 vs. 388.6±113.7 mm3, P=0.910). Our findings suggest that women referred to angiography for suspected ischemia, have differing patterns of coronary arterial response to injury with regard to accumulation of atherosclerosis and compensatory remodelling related to the presence and absence of obstructive CAD. Preservation and cultivation of compensatory arterial remodelling may be a novel CAD therapeutic target.