Publications by authors named "Habib Samady"

204 Publications

Association between Aortic Valve Calcification Progression and Coronary Atherosclerotic Plaque Volume Progression in the PARADIGM Registry.

Radiology 2021 May 11:202630. Epub 2021 May 11.

From the Division of Cardiology, Department of Internal Medicine, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul, South Korea (S.E.L.); Yonsei-Cedars-Sinai Integrative Cardiovascular Imaging Research Center, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea (S.E.L., J.M.S., H.J.C.); Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Yonsei University Health System, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea (J.M.S., S.S., H.J.C.); Centro Cardiologico Monzino, IRCCS, Milan, Italy (D.A., E.C., G.P.); Houston Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, Tex (M.H.A.); Department of Medicine, Los Angeles Biomedical Research Institute, Torrance, Calif (M.J.B.); Cardiovascular Imaging Unit, SDN IRCCS, Naples, Italy (F.C.); Department of Cardiology, William Beaumont Hospital, Royal Oak, Mich (K.C.); Pusan University Hospital, Busan, South Korea (J.H.C.); Seoul National University Bundang Hospital, Seongnam, South Korea (E.J.C.); Department of Radiology, Casa de Saude São Jose, Rio de Janeiro, Brazil (I.G.); Department of Radiology and Nuclear Medicine, German Heart Center Munich, Munich, Germany (M.H.); Department of Internal Medicine, Seoul National University College of Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul, South Korea (Y.J.K.); Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea (B.K.L.); Department of Medicine and Radiology, University of British Columbia, Vancouver, Canada (J.A.L.); Department of Radiology, Area Vasta 1/ASUR Marche, Urbino, Italy (E.M.); UNICA, Unit of Cardiovascular Imaging, Hospital da Luz, Lisbon, Portugal (H.M., P.d.A.G.); Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Mass (P.H.S.); Division of Cardiology, Emory University School of Medicine, Atlanta, Ga (H.S.); Department of Pathology, CVPath Institute, Gaithersburg, Md (R.V.); Icahn School of Medicine at Mount Sinai, New York, NY (J.N.); Department of Imaging and Medicine, Cedars-Sinai Medical Center, Los Angeles, Calif (D.S.B.); Department of Radiology, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, NY (L.J.S., F.Y.L., J.K.M.); Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands (J.J.B.).

Background Aortic valve calcification (AVC) is a key feature of aortic stenosis, and patients with aortic stenosis often have coronary -artery disease. Therefore, proving the association between the progression of AVC and coronary atherosclerosis could improve follow-up and treatment strategies. Purpose To explore the association between the progression of AVC and the progression of total and plaque volume composition from a large multicenter registry of serial coronary CT angiographic examinations. Materials and Methods A prospective multinational registry (PARADIGM) of consecutive participants who underwent serial coronary CT angiography at intervals of every 2 years or more was performed (January 2003-December 2015). AVC and the total and plaque volume composition at baseline and follow-up angiography were quantitatively analyzed. Plaque volumes were normalized by using the mean total analyzed vessel length of the study population. Multivariable linear mixed-effects models were constructed. Results Overall, 594 participants (mean age ± standard deviation, 62 years ± 10; 330 men) were included (mean interval between baseline and follow-up angiography, 3.9 years ± 1.5). At baseline, the AVC score was 31 Agatston units ± 117, and the normalized total plaque volume at baseline was 122 mm ± 219. After adjustment for age, sex, clinical risk factors, and medication use, AVC was independently associated with total plaque volume (standardized β = 0.24; 95% CI: 0.16, 0.32; < .001) and both calcified (β = 0.26; 95% CI: 0.18, 0.34; < .001) and noncalcified (β = 0.17; 95% CI: 0.08, 0.25; < .001) plaque volumes at baseline. The progression of AVC was associated with the progression of total plaque volume (β = 0.13; 95% CI: 0.03, 0.22; = .01), driven solely by calcified plaque volume (β = 0.24; 95% CI: 0.14, 0.34; < .001) but not noncalcified plaque volumes (β = -0.06; 95% CI: -0.14, 0.03; = .17). Conclusion The overall burden of coronary atherosclerosis was associated with aortic valve calcification at baseline. However, the progression of aortic valve calcification was associated with only the progression of calcified plaque volume but not with the -progression of noncalcified plaque volume. Clinical trial registration no. NCT02803411 © RSNA, 2021 See also the editorial by Sinitsyn in this issue.
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http://dx.doi.org/10.1148/radiol.2021202630DOI Listing
May 2021

Optical Coherence Tomography-Based Patient-Specific Residual Multi-Thrombus Coronary Plaque Models with Fluid-Structure Interaction for Better Treatment Decisions: A Biomechanical Modeling Case Study.

J Biomech Eng 2021 Apr 20. Epub 2021 Apr 20.

School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China; Mathematical Sciences Department, Worcester Polytechnic Institute, Worcester, MA 01609, USA.

Intracoronary thrombus from plaque erosion could cause fatal acute coronary syndrome (ACS). A conservative anti-thrombotic therapy has been proposed to treat ACS patients in lieu of stenting. It is speculated that the residual thrombus after aspiration thrombectomy would influence the prognosis of this treatment. However, biomechanical mechanisms affecting intracoronary thrombus remodeling and clinical outcome remain largely unknown. In vivo optical coherence tomography (OCT) data of a coronary plaque with two residual thrombi after anti-thrombotic therapy were acquired from an ACS patient with consent obtained. Three OCT-based FSI models with different thrombus volumes, fluid-only and structure-only models were constructed to simulate and compare the biomechanical interplay among blood flow, residual thrombus and vessel wall mimicking different clinical situations. Our results showed that residual thrombus would decrease coronary volumetric flow rate by 9.3%, but elevate wall shear stress (WSS) by 29.4% and 75.5% at Thrombus 1 & 2, respectively. WSS variations in a cardiac cycle from structure-only model were 12.1% and 13.5% higher at the two thrombus surfaces than those from FSI model. Intracoronary thrombi were subjected to compressive forces indicated by negative thrombus stress. Tandem intracoronary thrombus might influence coronary hemodynamics and solid mechanics differently. Computational modeling could be used to quantify biomechanical conditions under which patients could receive patient-specific treatment plan with optimized outcome after anti-thrombotic therapy. More patient studies with follow-up data are needed to continue the investigation and better understand mechanisms governing thrombus remodeling process.
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http://dx.doi.org/10.1115/1.4050911DOI Listing
April 2021

Predicting plaque vulnerability change using intravascular ultrasound + optical coherence tomography image-based fluid-structure interaction models and machine learning methods with patient follow-up data: a feasibility study.

Biomed Eng Online 2021 Apr 6;20(1):34. Epub 2021 Apr 6.

Department of Mathematics, Southeast University, Nanjing, 210096, China.

Background: Coronary plaque vulnerability prediction is difficult because plaque vulnerability is non-trivial to quantify, clinically available medical image modality is not enough to quantify thin cap thickness, prediction methods with high accuracies still need to be developed, and gold-standard data to validate vulnerability prediction are often not available. Patient follow-up intravascular ultrasound (IVUS), optical coherence tomography (OCT) and angiography data were acquired to construct 3D fluid-structure interaction (FSI) coronary models and four machine-learning methods were compared to identify optimal method to predict future plaque vulnerability.

Methods: Baseline and 10-month follow-up in vivo IVUS and OCT coronary plaque data were acquired from two arteries of one patient using IRB approved protocols with informed consent obtained. IVUS and OCT-based FSI models were constructed to obtain plaque wall stress/strain and wall shear stress. Forty-five slices were selected as machine learning sample database for vulnerability prediction study. Thirteen key morphological factors from IVUS and OCT images and biomechanical factors from FSI model were extracted from 45 slices at baseline for analysis. Lipid percentage index (LPI), cap thickness index (CTI) and morphological plaque vulnerability index (MPVI) were quantified to measure plaque vulnerability. Four machine learning methods (least square support vector machine, discriminant analysis, random forest and ensemble learning) were employed to predict the changes of three indices using all combinations of 13 factors. A standard fivefold cross-validation procedure was used to evaluate prediction results.

Results: For LPI change prediction using support vector machine, wall thickness was the optimal single-factor predictor with area under curve (AUC) 0.883 and the AUC of optimal combinational-factor predictor achieved 0.963. For CTI change prediction using discriminant analysis, minimum cap thickness was the optimal single-factor predictor with AUC 0.818 while optimal combinational-factor predictor achieved an AUC 0.836. Using random forest for predicting MPVI change, minimum cap thickness was the optimal single-factor predictor with AUC 0.785 and the AUC of optimal combinational-factor predictor achieved 0.847.

Conclusion: This feasibility study demonstrated that machine learning methods could be used to accurately predict plaque vulnerability change based on morphological and biomechanical factors from multi-modality image-based FSI models. Large-scale studies are needed to verify our findings.
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http://dx.doi.org/10.1186/s12938-021-00868-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025351PMC
April 2021

Atherogenic index of plasma and the risk of rapid progression of coronary atherosclerosis beyond traditional risk factors.

Atherosclerosis 2021 May 13;324:46-51. Epub 2021 Mar 13.

Department of Radiology, New York-Presbyterian Hospital and Weill Cornell Medicine, New York, NY, USA.

Background And Aims: The atherogenic index of plasma (AIP) has been suggested as a marker of plasma atherogenicity. This study aimed to assess the association between AIP and the rapid progression of coronary atherosclerosis using serial coronary computed tomography angiography (CCTA).

Methods: A total of 1488 adults (60.9 ± 9.2 years, 58.9% male) who underwent serial CCTA with a median inter-scan period of 3.4 years were included. AIP was defined as the base 10 logarithm of the ratio of the concentrations of triglyceride to high-density lipoprotein cholesterol. Rapid plaque progression (RPP) was defined as the change of percentage atheroma volume (PAV) ≥1.0%/year. All participants were divided into three groups based on AIP tertiles.

Results: Baseline total PAV (median [interquartile range (IQR)]) (%) (group I [lowest]: 1.91 [0.00, 6.21] vs. group II: 2.82 [0.27, 8.83] vs. group III [highest]: 2.70 [0.41, 7.50]), the annual change of total PAV (median [IQR]) (%/year) (group I: 0.27 [0.00, 0.81] vs. group II: 0.37 [0.04, 1.11] vs. group III: 0.45 [0.06, 1.25]), and the incidence of RPP (group I: 19.7% vs. group II: 27.3% vs. group III: 31.4%) were significantly different among AIP tertiles (all p < 0.05). In multiple logistic regression analysis, the risk of RPP was increased in group III (odds ratio: 1.52, 95% confidence interval: 1.02-2.26; p = 0.042) compared to group I after adjusting for clinical factors and baseline total PAV.

Conclusions: Based on serial CCTA findings, AIP is an independent predictive marker for RPP beyond traditional risk factors.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.03.009DOI Listing
May 2021

Multi-patient study for coronary vulnerable plaque model comparisons: 2D/3D and fluid-structure interaction simulations.

Biomech Model Mechanobiol 2021 Mar 23. Epub 2021 Mar 23.

Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30307, USA.

Several image-based computational models have been used to perform mechanical analysis for atherosclerotic plaque progression and vulnerability investigations. However, differences of computational predictions from those models have not been quantified at multi-patient level. In vivo intravascular ultrasound (IVUS) coronary plaque data were acquired from seven patients. Seven 2D/3D models with/without circumferential shrink, cyclic bending and fluid-structure interactions (FSI) were constructed for the seven patients to perform model comparisons and quantify impact of 2D simplification, circumferential shrink, FSI and cyclic bending plaque wall stress/strain (PWS/PWSn) and flow shear stress (FSS) calculations. PWS/PWSn and FSS averages from seven patients (388 slices for 2D and 3D thin-layer models) were used for comparison. Compared to 2D models with shrink process, 2D models without shrink process overestimated PWS by 17.26%. PWS change at location with greatest curvature change from 3D FSI models with/without cyclic bending varied from 15.07% to 49.52% for the seven patients (average = 30.13%). Mean Max-FSS, Min-FSS and Ave-FSS from the flow-only models under maximum pressure condition were 4.02%, 11.29% and 5.45% higher than those from full FSI models with cycle bending, respectively. Mean PWS and PWSn differences between FSI and structure-only models were only 4.38% and 1.78%. Model differences had noticeable patient variations. FSI and flow-only model differences were greater for minimum FSS predictions, notable since low FSS is known to be related to plaque progression. Structure-only models could provide PWS/PWSn calculations as good approximations to FSI models for simplicity and time savings in calculation.
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http://dx.doi.org/10.1007/s10237-021-01450-8DOI Listing
March 2021

Age and Functional Relevance of Coronary Stenosis: a Post-Hoc Analysis of the ADVISE II Trial.

EuroIntervention 2021 Mar 16. Epub 2021 Mar 16.

Interventional Cardiology Unit, Hospital Clinico San Carlos IDISSC, Complutense University of Madrid, Madrid, Spain.

Background: The influence of age-dependent changes on fractional flow reserve (FFR) or instantaneous free-wave ratio (iFR) and the response to pharmacological hyperaemia has not been investigated.

Aims: We investigated the impact of age on these indices.

Methods: This is as post-hoc analysis of the ADVISE II trial, including a total of 690 pressure recordings (in 591 patients). Age-dependent correlations with FFR and iFR were calculated and adjusted for stenosis severity. Patients were stratified into three age terciles. The hyperaemic response to adenosine, calculated as the difference between resting and hyperaemic pressure ratios, and the prevalence of FFR-iFR discordance were assessed.

Results: Age correlated positively with FFR (r=0.08, 95% CI: 0.01 to 0.15, p=0.015), but not with iFR (r=-0.03, 95% CI: -0.11 to 0.04, p=0.411). The hyperaemic response to adenosine decreased with patient age (0.12 ± 0.07, 0.11 ± 0.06, 0.09 ± 0.05, for the 1st[33-58 years], 2nd[59-69 years] and 3rd[70-94 years] age tertiles, respectively, p<0.001) and showed significant correlation with age (r=-0.14, 95% CI -0.21 to -0.06, p<0.001). The proportion of patients with FFR≤0.80 + iFR>0.89 discordance doubled in the first age-tercile (14.1% vs 7.1% vs 7.0%, p=0.005).

Conclusions: The hyperaemic response of the microcirculation to adenosine administration is age-dependent. FFR values increase with patient age, while iFR values remain constant across the age spectrum. These findings contribute to explain differences observed in functional stenosis classification with hyperaemic and non-hyperaemic coronary indices.
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http://dx.doi.org/10.4244/EIJ-D-20-01163DOI Listing
March 2021

Effects of chronic kidney disease and declining renal function on coronary atherosclerotic plaque progression: a PARADIGM substudy.

Eur Heart J Cardiovasc Imaging 2021 Mar 12. Epub 2021 Mar 12.

Division of Cardiology, Severance Cardiovascular Hospital, Integrative Cardiovascular Imaging Center, Yonsei University College of Medicine, Seoul, South Korea.

Aims : To investigate the change in atherosclerotic plaque volume in patients with chronic kidney disease (CKD) and declining renal function, using coronary computed tomography angiography (CCTA).

Methods And Results: In total, 891 participants with analysable serial CCTA and available glomerular filtration rate (GFR, derived using Cockcroft-Gault formulae) at baseline (CCTA 1) and follow-up (CCTA 2) were included. CKD was defined as GFR <60 mL/min/1.73 m2. Declining renal function was defined as ≥10% drop in GFR from the baseline. Quantitative assessment of plaque volume and composition were performed on both scans. There were 203 participants with CKD and 688 without CKD. CKD was associated with higher baseline total plaque volume, but similar plaque progression, measured by crude (57.5 ± 3.4 vs. 65.9 ± 7.7 mm3/year, P = 0.28) or annualized (17.3 ± 1.0 vs. 19.9 ± 2.0 mm3/year, P = 0.25) change in total plaque volume. There were 709 participants with stable GFR and 182 with declining GFR. Declining renal function was independently associated with plaque progression, with higher crude (54.1 ± 3.2 vs. 80.2 ± 9.0 mm3/year, P < 0.01) or annualized (16.4 ± 0.9 vs. 23.9 ± 2.6 mm3/year, P < 0.01) increase in total plaque volume. In CKD, plaque progression was driven by calcified plaques whereas in patients with declining renal function, it was driven by non-calcified plaques.

Conclusion: Decline in renal function was associated with more rapid plaque progression, whereas the presence of CKD was not.
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http://dx.doi.org/10.1093/ehjci/jeab029DOI Listing
March 2021

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

JACC Cardiovasc Imaging 2021 Jan 13. Epub 2021 Jan 13.

Department of Pathology, CVPath Institute, Gaithersburg, Maryland, USA.

Objectives: This study sought to identify distinct patient groups and their association with outcome based on the patient similarity network using quantitative coronary plaque characteristics from coronary computed tomography angiography (CTA).

Background: Coronary CTA can noninvasively assess coronary plaques quantitatively.

Methods: Patients who underwent 2 coronary CTAs at a minimum of 24 months' interval were analyzed (n = 1,264). A similarity Mapper network of patients was built by topological data analysis (TDA) based on the whole-heart quantitative coronary plaque analysis on coronary CTA to identify distinct patient groups and their association with outcome.

Results: Three distinct patient groups were identified by TDA, and the patient similarity network by TDA showed a closed loop, demonstrating a continuous trend of coronary plaque progression. Group A had the least coronary plaque amount (median 12.4 mm [interquartile range (IQR): 0.0 to 39.6 mm]) in the entire coronary tree. Group B had a moderate coronary plaque amount (31.7 mm [IQR: 0.0 to 127.4 mm]) with relative enrichment of fibrofatty and necrotic core (32.6% [IQR: 16.7% to 46.2%] and 2.7% [IQR: 0.1% to 6.9%] of the total plaque, respectively) components. Group C had the largest coronary plaque amount (187.0 mm [IQR: 96.7 to 306.4 mm]) and was enriched for dense calcium component (46.8% [IQR: 32.0% to 63.7%] of the total plaque). At follow-up, total plaque volume, fibrous, and dense calcium volumes increased in all groups, but the proportion of fibrofatty component decreased in groups B and C, whereas the necrotic core portion decreased in only group B (all p < 0.05). Group B showed a higher acute coronary syndrome incidence than other groups (0.3% vs. 2.6% vs. 0.6%; p = 0.009) but both group B and C had a higher revascularization incidence than group A (3.1% vs. 15.5% vs. 17.8%; p < 0.001). Incorporating group information from TDA demonstrated increase of model fitness for predicting acute coronary syndrome or revascularization compared with that incorporating clinical risk factors, percentage diameter stenosis, and high-risk plaque features.

Conclusions: The TDA of quantitative whole-heart coronary plaque characteristics on coronary CTA identified distinct patient groups with different plaque dynamics and clinical outcomes. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411).
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http://dx.doi.org/10.1016/j.jcmg.2020.11.009DOI Listing
January 2021

Progression of whole-heart Atherosclerosis by coronary CT and major adverse cardiovascular events.

J Cardiovasc Comput Tomogr 2021 Jan 1. Epub 2021 Jan 1.

Department of Imaging and Medicine, Cedars Sinai Medical Center, Los Angeles, CA, USA.

Background: The current study aimed to examine the independent prognostic value of whole-heart atherosclerosis progression by serial coronary computed tomography angiography (CCTA) for major adverse cardiovascular events (MACE).

Methods: The multi-center PARADIGM study includes patients undergoing serial CCTA for symptomatic reasons, ≥2 years apart. Whole-heart atherosclerosis was characterized on a segmental level, with co-registration of baseline and follow-up CCTA, and summed to per-patient level. The independent prognostic significance of atherosclerosis progression for MACE (non-fatal myocardial infarction [MI], death, unplanned coronary revascularization) was examined. Patients experiencing interval MACE were not omitted.

Results: The study population comprised 1166 patients (age 60.5 ​± ​9.5 years, 54.7% male) who experienced 139 MACE events during 8.2 (IQR 6.2, 9.5) years of follow up (15 death, 5 non-fatal MI, 119 unplanned revascularizations). Whole-heart percent atheroma volume (PAV) increased from 2.32% at baseline to 4.04% at follow-up. Adjusted for baseline PAV, the annualized increase in PAV was independently associated with MACE: OR 1.23 (95% CI 1.08, 1.39) per 1 standard deviation increase, which was consistent in multiple subpopulations. When categorized by composition, only non-calcified plaque progression associated independently with MACE, while calcified plaque did not. Restricting to patients without events before follow-up CCTA, those with future MACE showed an annualized increase in PAV of 0.93% (IQR 0.34, 1.96) vs 0.32% (IQR 0.02, 0.90), P ​< ​0.001.

Conclusions: Whole-heart atherosclerosis progression examined by serial CCTA is independently associated with MACE, with a prognostic threshold of 1.0% increase in PAV per year.
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http://dx.doi.org/10.1016/j.jcct.2020.12.007DOI Listing
January 2021

Relationship between high shear stress and OCT-verified thin-cap fibroatheroma in patients with coronary artery disease.

PLoS One 2020 17;15(12):e0244015. Epub 2020 Dec 17.

Division of Cardiology, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.

High-risk coronary plaques have been considered predictive of adverse cardiac events. Both wall shear stress (WSS) in patients with hemodynamically significant lesions and optical coherence tomography (OCT) -verified thin-cap fibroatheroma (TCFA) are associated with plaque rupture, the most common underlying mechanism of acute coronary syndrome. The aim of the study was to test the hypothesis that invasive coronary angiography-based high WSS is associated with the presence of TCFA detected by OCT in obstructive lesions. From a prospective study of patients who underwent OCT examination for angiographically obstructive lesions (Yellow II), we selected patients who had two angiographic projections to create a 3-dimensional reconstruction model to allow assessment of WSS. The patients were divided into 2 groups according to the presence and absence of TCFA. Mean WSS was assessed in the whole lesion and in the proximal, middle and distal segments. Of 70 patients, TCFA was observed in 13 (19%) patients. WSS in the proximal segment (WSSproximal) (10.20 [5.01, 16.93Pa]) and the whole lesion (WSSlesion) (12.37 [6.36, 14.55Pa]) were significantly higher in lesions with TCFA compared to WSSproximal (5.84 [3.74, 8.29Pa], p = 0.02) and WSSlesion (6.95 [4.41, 11.60], p = 0.04) in lesions without TCFA. After multivariate analysis, WSSproximal was independently associated with the presence of TCFA (Odds ratio 1.105; 95%CI 1.007-1.213, p = 0.04). The optimal cutoff value of WSSproximal to predict TCFA was 6.79 Pa (AUC: 0.71; sensitivity: 0.77; specificity: 0.63 p = 0.02). Our results demonstrate that high WSS in the proximal segments of obstructive lesions is an independent predictor of OCT-verified TCFA.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244015PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746187PMC
February 2021

Microvascular Assessment of Ranolazine in Non-Obstructive Atherosclerosis: The MARINA Randomized, Double-Blinded, Controlled Pilot Trial.

Circ Cardiovasc Interv 2020 Dec 4;13(12):e008204. Epub 2020 Dec 4.

Andreas Gruentzig Cardiovascular Center, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (J.-S.K., O.Y.H., P.E., R.R., M.R., S.K., S.G., H.H., N.S., G.M.B., C.L., P.K.M., A.A.Q., H.S.).

Background: Microvascular dysfunction is known to play a key role in patients with angina and nonobstructive coronary artery disease. We investigated the impact of ranolazine among patients with angina and nonobstructive coronary artery disease.

Methods: In this randomized, double-blinded, placebo-controlled pilot trial, 26 patients with angina once weekly or more, abnormal stress test, and nonobstructive coronary artery disease (<50% stenosis by angiography and fractional flow reserve >0.80) were randomized 1:1 to ranolazine or placebo for 12 weeks. Primary end point was ΔSeattle Angina Questionnaire (SAQ) angina frequency score. Baseline and 3 months follow-up SAQ, Duke Activity Status Index scores along with invasive fractional flow reserve, coronary flow reserve (CFR), hyperemic myocardial resistance, and cardiopulmonary exercise testing measurements were performed.

Results: No significant differences in ΔSAQ angina frequency scores (=0.53) or Duke Activity Status Index (=0.76) were observed between ranolazine versus placebo, although patients on ranolazine had lesser improvement in SAQ physical limitation scores (=0.02) compared with placebo at 3 months. There were no significant differences in ΔCFR or Δhyperemic myocardial resistance between ranolazine and placebo groups. Patients treated with ranolazine, compared with placebo, had no significant improvement in maximum rate of oxygen consumption measured during incremental exercise (VO max) and peak metabolic equivalents of task. Interestingly, in the ranolazine group, patients with baseline CFR<2.0 demonstrated greater gain in CFR compared with those with baseline CFR≥2.0 (=0.02).

Conclusions: Ranolazine did not demonstrate improvement in SAQ angina frequency score, invasive microvascular function, or peak metabolic equivalent compared with placebo at 3 months. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02147067.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.119.008204DOI Listing
December 2020

Using optical coherence tomography and intravascular ultrasound imaging to quantify coronary plaque cap thickness and vulnerability: a pilot study.

Biomed Eng Online 2020 Nov 30;19(1):90. Epub 2020 Nov 30.

School of Biological Science and Medical Engineering, Southeast University, #2 SiPailou, Nanjing, China.

Background: Detecting coronary vulnerable plaques in vivo and assessing their vulnerability have been great challenges for clinicians and the research community. Intravascular ultrasound (IVUS) is commonly used in clinical practice for diagnosis and treatment decisions. However, due to IVUS limited resolution (about 150-200 µm), it is not sufficient to detect vulnerable plaques with a threshold cap thickness of 65 µm. Optical Coherence Tomography (OCT) has a resolution of 15-20 µm and can measure fibrous cap thickness more accurately. The aim of this study was to use OCT as the benchmark to obtain patient-specific coronary plaque cap thickness and evaluate the differences between OCT and IVUS fibrous cap quantifications. A cap index with integer values 0-4 was also introduced as a quantitative measure of plaque vulnerability to study plaque vulnerability.

Methods: Data from 10 patients (mean age: 70.4; m: 6; f: 4) with coronary heart disease who underwent IVUS, OCT, and angiography were collected at Cardiovascular Research Foundation (CRF) using approved protocol with informed consent obtained. 348 slices with lipid core and fibrous caps were selected for study. Convolutional Neural Network (CNN)-based and expert-based data segmentation were performed using established methods previously published. Cap thickness data were extracted to quantify differences between IVUS and OCT measurements.

Results: For the 348 slices analyzed, the mean value difference between OCT and IVUS cap thickness measurements was 1.83% (p = 0.031). However, mean value of point-to-point differences was 35.76%. Comparing minimum cap thickness for each plaque, the mean value of the 20 plaque IVUS-OCT differences was 44.46%, ranging from 2.36% to 91.15%. For cap index values assigned to the 348 slices, the disagreement between OCT and IVUS assignments was 25%. However, for the OCT cap index = 2 and 3 groups, the disagreement rates were 91% and 80%, respectively. Furthermore, the observation of cap index changes from baseline to follow-up indicated that IVUS results differed from OCT by 80%.

Conclusions: These preliminary results demonstrated that there were significant differences between IVUS and OCT plaque cap thickness measurements. Large-scale patient studies are needed to confirm our findings.
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http://dx.doi.org/10.1186/s12938-020-00832-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706023PMC
November 2020

The Relationship Between Coronary Calcification and the Natural History of Coronary Artery Disease.

JACC Cardiovasc Imaging 2021 Jan 18;14(1):233-242. Epub 2020 Nov 18.

Department of Cardiology, Heart Lung Center, Leiden University Medical Center, Leiden, the Netherlands.

Objectives: The aim of the current study was to explore the impact of plaque calcification in terms of absolute calcified plaque volume (CPV) and in the context of its percentage of the total plaque volume at a lesion and patient level on the progression of coronary artery disease.

Background: Coronary artery calcification is an established marker of risk of future cardiovascular events. Despite this, plaque calcification is also considered a marker of plaque stability, and it increases in response to medical therapy.

Methods: This analysis included 925 patients with 2,568 lesions from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry, in which patients underwent clinically indicated serial coronary computed tomography angiography. Plaque calcification was examined by using CPV and percent CPV (PCPV), calculated as (CPV/plaque volume) × 100 at a per-plaque and per-patient level (summation of all individual plaques).

Results: CPV was strongly correlated with plaque volume (r = 0.780; p < 0.001) at baseline and with plaque progression (r = 0.297; p < 0.001); however, this association was reversed after accounting for plaque volume at baseline (r = -0.146; p < 0.001). In contrast, PCPV was an independent predictor of a reduction in plaque volume (r = -0.11; p < 0.001) in univariable and multivariable linear regression analyses. Patient-level analysis showed that high CPV was associated with incident major adverse cardiac events (hazard ratio: 3.01: 95% confidence interval: 1.58 to 5.72), whereas high PCPV was inversely associated with major adverse cardiac events (hazard ratio: 0.529; 95% confidence interval: 0.229 to 0.968) in multivariable analysis.

Conclusions: Calcified plaque is a marker for risk of adverse events and disease progression due to its strong association with the total plaque burden. When considered as a percentage of the total plaque volume, increasing PCPV is a marker of plaque stability and reduced risk at both a lesion and patient level. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411).
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http://dx.doi.org/10.1016/j.jcmg.2020.08.036DOI Listing
January 2021

Comparative differences in the atherosclerotic disease burden between the epicardial coronary arteries: quantitative plaque analysis on coronary computed tomography angiography.

Eur Heart J Cardiovasc Imaging 2021 Feb;22(3):322-330

Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Aims: Anatomic series commonly report the extent and severity of coronary artery disease (CAD), regardless of location. The aim of this study was to evaluate differences in atherosclerotic plaque burden and composition across the major epicardial coronary arteries.

Methods And Results: A total of 1271 patients (age 60 ± 9 years; 57% men) with suspected CAD prospectively underwent coronary computed tomography angiography (CCTA). Atherosclerotic plaque volume was quantified with categorization by composition (necrotic core, fibrofatty, fibrous, and calcified) based on Hounsfield Unit density. Per-vessel measures were compared using generalized estimating equation models. On CCTA, total plaque volume was lowest in the LCx (10.0 ± 29.4 mm3), followed by the RCA (32.8 ± 82.7 mm3; P < 0.001), and LAD (58.6 ± 83.3 mm3; P < 0.001), even when correcting for vessel length or volume. The prevalence of ≥2 high-risk plaque features, such as positive remodelling or spotty calcification, occurred less in the LCx (3.8%) when compared with the LAD (21.4%) or RCA (10.9%, P < 0.001). In the LCx, the most stenotic lesion was categorized as largely calcified more often than in the RCA and LAD (55.3% vs. 39.4% vs. 32.7%; P < 0.001). Median diameter stenosis was also lowest in the LCx (16.2%) and highest in the LAD (21.3%; P < 0.001) and located more distal along the LCx when compared with the RCA and LAD (P < 0.001).

Conclusion: Atherosclerotic plaque, irrespective of vessel volume, varied across the epicardial coronary arteries; with a significantly lower burden and different compositions in the LCx when compared with the LAD and RCA. These volumetric and compositional findings support a diverse milieu for atherosclerotic plaque development and may contribute to a varied acute coronary risk between the major epicardial coronary arteries.
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http://dx.doi.org/10.1093/ehjci/jeaa275DOI Listing
February 2021

Impact of adherence to the hybrid algorithm for initial crossing strategy selection in chronic total occlusion percutaneous coronary intervention.

Rev Esp Cardiol (Engl Ed) 2020 Nov 12. Epub 2020 Nov 12.

Coronary Artery Disease Science Center, Minneapolis Heart Institute, Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, Minneapolis, Minnesota, United States.

Introduction And Objectives: The hybrid algorithm was designed to assist with initial and subsequent crossing strategy selection in chronic total occlusion (CTO) percutaneous coronary interventions (PCIs). However, the success of the initially selected strategy has received limited study.

Methods: We examined the impact of adherence to the hybrid algorithm recommendation for initial CTO crossing technique selection in 4178 CTO PCIs from a large multicenter registry.

Results: The initial crossing strategy was concordant with the hybrid algorithm recommendation in 1833 interventions (44%). Patients in the concordant group had a similar age to those in the discordant group but a lower mean J-CTO score (2.0 ± 1.4 vs 2.8 ± 1.1; P < .01). The concordant group showed higher technical success with the first crossing strategy (68% vs 48%; P < .01) and higher overall technical success (88% vs 83%; P < .01) with no difference in the incidence of in-hospital major adverse events (1.8% vs 2.3%; P = .26). In multivariable analysis, after adjustment for age, prior myocardial infarction, prior PCI, prior coronary artery bypass grafting, J-CTO score, and scheduled CTO PCI, nonadherence to the hybrid algorithm was independently associated with lower technical success of the initial crossing strategy (odds ratio, 0.55; 95% confidence interval, 0.48-0.64; P < .01).

Conclusions: Adherence to the hybrid algorithm for initial crossing strategy selection is associated with higher CTO PCI success but similar in-hospital major adverse cardiac events.
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http://dx.doi.org/10.1016/j.rec.2020.09.009DOI Listing
November 2020

Impact of age on coronary artery plaque progression and clinical outcome: A PARADIGM substudy.

J Cardiovasc Comput Tomogr 2020 Oct 1. Epub 2020 Oct 1.

Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Background: The association of age with coronary plaque dynamics is not well characterized by coronary computed tomography angiography (CCTA).

Methods: From a multinational registry of patients who underwent serial CCTA, 1153 subjects (61 ± 5 years old, 61.1% male) were analyzed. Annualized volume changes of total, fibrous, fibrofatty, necrotic core, and dense calcification plaque components of the whole heart were compared by age quartile groups. Clinical events, a composite of all-cause death, acute coronary syndrome, and any revascularization after 30 days of the initial CCTA, were also analyzed. Random forest analysis was used to define the relative importance of age on plaque progression.

Results: With a 3.3-years' median interval between the two CCTA, the median annual volume changes of total plaque in each age quartile group was 7.8, 10.5, 10.8, and 12.1 mm/year and for dense calcification, 2.5, 4.6, 5.4, and 7.1 mm/year, both of which demonstrated a tendency to increase by age (p-for-trend = 0.001 and < 0.001, respectively). However, this tendency was not observed in any other plaque components. The annual volume changes of total plaque and dense calcification were also significantly different in the propensity score-matched lowest age quartile group versus the other age groups as was the composite clinical event (log-rank p = 0.003). In random forest analysis, age had comparable importance in the total plaque volume progression as other traditional factors.

Conclusions: The rate of whole-heart plaque progression and dense calcification increases depending on age. Age is a significant factor in plaque growth, the importance of which is comparable to other traditional risk factors.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02803411.
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http://dx.doi.org/10.1016/j.jcct.2020.09.009DOI Listing
October 2020

Functional coronary angiography in symptomatic patients with no obstructive coronary artery disease.

Catheter Cardiovasc Interv 2020 Sep 9. Epub 2020 Sep 9.

Division of Cardiology, Department of Internal Medicine, Emory Clinical Cardiovascular Research Institute, Atlanta, Georgia, USA.

Background: Patients without obstructive coronary artery disease (CAD) may have epicardial or microvascular dysfunction. The purpose of this study was to characterize patterns of epicardial and microvascular dysfunction in men and women with stable and unstable angina undergoing functional coronary angiography to inform medical therapy.

Methods: 163 symptomatic patients with ≤50% diameter stenosis and fractional flow reserve (FFR) > 0.8 underwent endothelium-dependent epicardial and microvascular function after intracoronary acetylcholine (10 M, 81 mcg over 3 minutes). Endothelium-independent function was assessed using coronary flow reserve (CFR) and hyperemic microvascular resistance (HMR) after intravenous adenosine (140 ug/kg/min). Coronary microvascular dysfunction (CMD) was defined as CFR < 2.5, HMR ≥2, or ≤50% change in coronary blood flow with acetylcholine (CBF ).

Results: Seventy-two percent had endothelial-dependent epicardial dysfunction (response to ACH: % ∆ in coronary artery diameter and ∆%CBF ) and 92% had CMD. Among CMD patients, 65% had CFR < 2.5, 35% had HMR ≥2, and 60% had CBF change ≤50%. CFR modestly correlated with HMR (r = -0.38, p < .0001). Among patients with normal CFR, 26% had abnormal epicardial and 20% had abnormal microvascular endothelial dysfunction. Women had a lower CFR (p = .02), higher FFR (p = .03) compared to men. There were no differences in epicardial and microvascular function between patients with stable and unstable angina.

Conclusion: In patients with no obstructive CAD: CMD is prevalent, abnormal CFR does not correlate with epicardial or microvascular endothelial dysfunction, women have lower CFR, higher FFR but similar endothelial function compared to men.
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http://dx.doi.org/10.1002/ccd.29237DOI Listing
September 2020

Coronary Computed Tomography Angiography From Clinical Uses to Emerging Technologies: JACC State-of-the-Art Review.

J Am Coll Cardiol 2020 09;76(10):1226-1243

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Electronic address:

Evaluation of coronary artery disease (CAD) using coronary computed tomography angiography (CCTA) has seen a paradigm shift in the last decade. Evidence increasingly supports the clinical utility of CCTA across various stages of CAD, from the detection of early subclinical disease to the assessment of acute chest pain. Additionally, CCTA can be used to noninvasively quantify plaque burden and identify high-risk plaque, aiding in diagnosis, prognosis, and treatment. This is especially important in the evaluation of CAD in immune-driven conditions with increased cardiovascular disease prevalence. Emerging applications of CCTA based on hemodynamic indices and plaque characterization may provide personalized risk assessment, affect disease detection, and further guide therapy. This review provides an update on the evidence, clinical applications, and emerging technologies surrounding CCTA as highlighted at the 2019 National Heart, Lung and Blood Institute CCTA Summit.
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http://dx.doi.org/10.1016/j.jacc.2020.06.076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480405PMC
September 2020

Adverse clinical outcomes in patients undergoing both PCI and TAVR: Analysis from a pooled multi-center registry.

Catheter Cardiovasc Interv 2021 Feb 26;97(3):529-539. Epub 2020 Aug 26.

Andreas Gruentzig Cardiovascular Center, Emory University School of Medicine, Atlanta, Georgia.

Background: There is a paucity of data regarding the optimum timing of PCI in relation to TAVR.

Objective: We compared the major adverse cardiovascular and cerebrovascular events (MACCE) rates among patients who underwent percutaneous coronary intervention (PCI) before transcatheter aortic valve replacement (TAVR) with those who received PCI with/after TAVR.

Methods: In this multicenter study, we pooled all consecutive patients who underwent TAVR at three high volume centers.

Results: Among 3,982 patients who underwent TAVR, 327 (8%) patients underwent PCI within 1 year before TAVR, 38 (1%) had PCI the same day as TAVR and 15 (0.5%) had PCI within 2 months after TAVR. Overall, among patients who received both PCI and TAVR (n = 380), history of previous CABG (HR:0.501; p = .001), higher BMI at TAVR (HR:0.970; p = .038), and statin therapy after TAVR (HR:0.660, p = .037) were independently associated with lower MACCE while warfarin therapy after TAVR was associated with a higher risk of MACCE (HR:1.779, p = .017). Patients who received PCI within 1 year before TAVR had similar baseline demographics, STS scores, clinical risk factors when compared to patients receiving PCI with/after TAVR. Both groups were similar in PCI (Syntax Score, ACC/AHA lesion class) and TAVR (valve types, access) related variables. There were no significant differences in terms of MACCE (log rank p = .550), all-cause mortality (log rank p = .433), strokes (log rank p = .153), and repeat PCI (log rank p = .054) in patients who underwent PCI with/after TAVR when compared to patients who received PCI before TAVR.

Conclusion: Among patients who underwent both PCI and TAVR, history of CABG, higher BMI, and statin therapy had lower, while those discharged on warfarin, had higher adverse event rates. Adverse events rates were similar regardless of timing of PCI.
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http://dx.doi.org/10.1002/ccd.29233DOI Listing
February 2021

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

JACC Cardiovasc Imaging 2020 11 19;13(11):2386-2396. Epub 2020 Aug 19.

Yonsei-Cedars-Sinai Integrative Cardiovascular Imaging Research Center, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea; Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea. Electronic address:

Objectives: This study sought to explore sex-based differences in total and compositional plaque volume (PV) progression.

Background: It is unclear whether sex has an impact on PV progression in patients with coronary artery disease (CAD).

Methods: The study analyzed a prospective multinational registry of consecutive patients with suspected CAD who underwent 2 or more clinically indicated coronary computed tomography angiography (CTA) at ≥2-year intervals. Total and compositional PV at baseline and follow-up were quantitatively analyzed and normalized using the analyzed total vessel length. Multivariate linear regression models were constructed.

Results: Of the 1,255 patients included (median coronary CTA interval 3.8 years), 543 were women and 712 were men. Women were older (62 ± 9 years of age vs. 59 ± 9 years of age; p < 0.001) and had higher total cholesterol levels (195 ± 41 mg/dl vs. 187 ± 39 mg/dl; p = 0.002). Prevalence of hypertension, diabetes, and family history of CAD were not different (all p > 0.05). At baseline, men possessed greater total PV (31.3 mm [interquartile range (IQR): 0 to 121.8 mm] vs. 56.7 mm [IQR: 6.8 to 152.1 mm] p = 0.005), and there was an approximately 9-year delay in women in developing total PV than in men. The prevalence of high-risk plaques was greater in men than women (31% vs. 20%; p < 0.001). In multivariate analysis, after adjusting for age, clinical risk factors, medication use, and total PV at baseline, despite similar total PV progression rates, female sex was associated with greater calcified PV progression (β = 2.83; p = 0.004) but slower noncalcified PV progression (β = -3.39; p = 0.008) and less development of high-risk plaques (β = -0.18; p = 0.049) than in men.

Conclusions: The compositional PV progression differed according to sex, suggesting that comprehensive plaque evaluation may contribute to further refining of risk stratification according to sex. (NCT02803411).
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http://dx.doi.org/10.1016/j.jcmg.2020.06.034DOI Listing
November 2020

Age- and sex-related features of atherosclerosis from coronary computed tomography angiography in patients prior to acute coronary syndrome: results from the ICONIC study.

Eur Heart J Cardiovasc Imaging 2021 Jan;22(1):24-33

Division of Cardiology, Department of Internal Medicine, Hangyang University Medical Center, Seoul, Korea.

Aims: Although there is increasing evidence supporting coronary atherosclerosis evaluation by coronary computed tomography angiography (CCTA), no data are available on age and sex differences for quantitative plaque features. The aim of this study was to investigate sex and age differences in both qualitative and quantitative atherosclerotic features from CCTA prior to acute coronary syndrome (ACS).

Methods And Results: Within the ICONIC study, in which 234 patients with subsequent ACS were propensity matched 1:1 with 234 non-event controls, our current subanalysis included only the ACS cases. Both qualitative and quantitative advance plaque analysis by CCTA were performed by a core laboratory. In 129 cases, culprit lesions identified by invasive coronary angiography at the time of ACS were co-registered to baseline CCTA precursor lesions. The study population was then divided into subgroups according to sex and age (<65 vs. ≥ 65 years old) for analysis. Older patients had higher total plaque volume than younger patients. Within specific subtypes of plaque volume, however, only calcified plaque volume was higher in older patients (135.9 ± 163.7 vs. 63.8 ± 94.2 mm3, P < 0.0001, respectively). Although no sex-related differences were recorded for calcified plaque volume, females had lower fibrous and fibrofatty plaque volume than males (Fibrofatty volume 29.6 ± 44.1 vs. 75.3 ± 98.6 mm3, P = 0.0001, respectively). No sex-related differences in the prevalence of qualitative high-risk plaque features were found, even after separate analyses considering age were performed.

Conclusion: Our data underline the importance of age- and sex-related differences in coronary atherosclerosis presentation, which should be considered during CCTA-based atherosclerosis quantification.
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http://dx.doi.org/10.1093/ehjci/jeaa210DOI Listing
January 2021

Per-lesion versus per-patient analysis of coronary artery disease in predicting the development of obstructive lesions: the Progression of AtheRosclerotic PlAque DetermIned by Computed TmoGraphic Angiography Imaging (PARADIGM) study.

Int J Cardiovasc Imaging 2020 12 10;36(12):2357-2364. Epub 2020 Aug 10.

Yonsei-Cedars-Sinai Integrative Cardiovascular Imaging Research Center, Yonsei University College of Medicine, Yonsei University Health System, Seoul, South Korea.

To determine whether the assessment of individual plaques is superior in predicting the progression to obstructive coronary artery disease (CAD) on serial coronary computed tomography angiography (CCTA) than per-patient assessment. From a multinational registry of 2252 patients who underwent serial CCTA at a ≥ 2-year inter-scan interval, patients with only non-obstructive lesions at baseline were enrolled. CCTA was quantitatively analyzed at both the per-patient and per-lesion level. Models predicting the development of an obstructive lesion at follow up using either the per-patient or per-lesion level CCTA measures were constructed and compared. From 1297 patients (mean age 60 ± 9 years, 43% men) enrolled, a total of 3218 non-obstructive lesions were identified at baseline. At follow-up (inter-scan interval: 3.8 ± 1.6 years), 76 lesions (2.4%, 60 patients) became obstructive, defined as > 50% diameter stenosis. The C-statistics of Model 1, adjusted only by clinical risk factors, was 0.684. The addition of per-patient level total plaque volume (PV) and the presence of high-risk plaque (HRP) features to Model 1 improved the C-statistics to 0.825 [95% confidence interval (CI) 0.823-0.827]. When per-lesion level PV and the presence of HRP were added to Model 1, the predictive value of the model improved the C-statistics to 0.895 [95% CI 0.893-0.897]. The model utilizing per-lesion level CCTA measures was superior to the model utilizing per-patient level CCTA measures in predicting the development of an obstructive lesion (p < 0.001). Lesion-level analysis of coronary atherosclerotic plaques with CCTA yielded better predictive power for the development of obstructive CAD than the simple quantification of total coronary atherosclerotic burden at a per-patient level.Clinical Trial Registration: ClinicalTrials.gov NCT0280341.
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http://dx.doi.org/10.1007/s10554-020-01960-zDOI Listing
December 2020

Anatomy, Physiology, and Biomechanics: The Dream of Identifying Vulnerable Plaque Remains Alive.

JACC Cardiovasc Imaging 2020 10 5;13(10):2220-2222. Epub 2020 Aug 5.

Andreas Gruentzig Cardiovascular Center, Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia; Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

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http://dx.doi.org/10.1016/j.jcmg.2020.03.026DOI Listing
October 2020

Association of Cardiovascular Disease Risk Factor Burden With Progression of Coronary Atherosclerosis Assessed by Serial Coronary Computed Tomographic Angiography.

JAMA Netw Open 2020 07 1;3(7):e2011444. Epub 2020 Jul 1.

Cleerly, Inc, New York, New York.

Importance: Several studies have reported that the progression of coronary atherosclerosis, as measured by serial coronary computed tomographic (CT) angiography, is associated with the risk of future cardiovascular events. However, the cumulative consequences of multiple risk factors for plaque progression and the development of adverse plaque characteristics have not been well characterized.

Objectives: To examine the association of cardiovascular risk factor burden, as assessed by atherosclerotic cardiovascular disease (ASCVD) risk score, with the progression of coronary atherosclerosis and the development of adverse plaque characteristics.

Design, Setting, And Participants: This cohort study is a subgroup analysis of participant data from the prospective observational Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging (PARADIGM) study, which evaluated the association between serial coronary CT angiography findings and clinical presentation. The PARADIGM international multicenter registry, which includes 13 centers in 7 countries (Brazil, Canada, Germany, Italy, Portugal, South Korea, and the US), was used to identify 1005 adult patients without known coronary artery disease who underwent serial coronary CT angiography scans (median interscan interval, 3.3 years; interquartile range [IQR], 2.6-4.8 years) between December 24, 2003, and December 16, 2015. Based on the 10-year ASCVD risk score, the cardiovascular risk factor burden was classified as low (<7.5%), intermediate (7.5%-20.0%), or high (>20.0%). Data were analyzed from February 8, 2019, to April 17, 2020.

Exposures: Association of baseline ASCVD risk burden with plaque progression.

Main Outcomes And Measures: Noncalcified plaque, calcified plaque, and total plaque volumes (mm3) were measured. Noncalcified plaque was subclassified using predefined Hounsfield unit thresholds for fibrous, fibrofatty, and low-attenuation plaque. The percent atheroma volume (PAV) was defined as plaque volume divided by vessel volume. Adverse plaque characteristics were defined as the presence of positive remodeling, low-attenuation plaque, or spotty calcification.

Results: In total, 1005 patients (mean [SD] age, 60 [8] years; 575 men [57.2%]) were included in the analysis. Of those, 463 patients (46.1%) had a low 10-year ASCVD risk score (low-risk group), 373 patients (37.1%) had an intermediate ASCVD risk score (intermediate-risk group), and 169 patients (16.8%) had a high ASCVD risk score (high-risk group). The annualized progression rate of PAV for total plaque, calcified plaque, and noncalcified plaque was associated with increasing ASCVD risk (r = 0.26 for total plaque, r = 0.23 for calcified plaque, and r = 0.11 for noncalcified plaque; P < .001). The annualized PAV progression of total plaque, calcified plaque, and noncalcified plaque was significantly greater in the high-risk group compared with the low-risk and intermediate-risk groups (for total plaque, 0.99% vs 0.45% and 0.58%, respectively; P < .001; for calcified plaque, 0.61% vs 0.23% and 0.36%; P < .001; and for noncalcified plaque, 0.38%vs 0.22% and 0.23%; P = .01). When further subclassified by noncalcified plaque type, the annualized PAV progression of fibrofatty and low-attenuation plaque was greater in the high-risk group (0.09% and 0.02%, respectively) compared with the low- to intermediate-risk group (n = 836; 0.02% [P = .02] and 0.001% [P = .008], respectively). The interval development of adverse plaque characteristics was greater in the high-risk group compared with the low-risk and intermediate-risk groups (for new positive remodeling, 73 patients [43.2%] vs 151 patients [32.6%] and 133 patients [35.7%], respectively; P = .02; for new low-attenuation plaque, 26 patients [15.4%] vs 44 patients [9.5%] and 35 patients [9.4%]; P = .02; and for new spotty calcification, 37 patients [21.9%] vs 52 patients [11.2%] and 54 patients [14.5%]; P = .002). The progression of noncalcified plaque subclasses and the interval development of adverse plaque characteristics did not significantly differ between the low-risk and intermediate-risk groups.

Conclusions And Relevance: Progression of coronary atherosclerosis occurred across all ASCVD risk groups and was associated with an increase in 10-year ASCVD risk. The progression of fibrofatty and low-attenuation plaques and the development of adverse plaque characteristics was greater in patients with a high risk of ASCVD.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.11444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382001PMC
July 2020

Impact of Intravascular Ultrasound Utilization for Stent Optimization on 1-Year Outcomes After Chronic Total Occlusion Percutaneous Coronary Intervention.

J Invasive Cardiol 2020 Oct 22;32(10):392-399. Epub 2020 Jul 22.

Background: The impact of intravascular ultrasound (IVUS) utilization for stent optimization on the long-term outcomes in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study.

Methods: We examined the outcomes of CTO-PCI with and without IVUS use for stent optimization in 922 CTO-PCIs performed between 2012 and 2019 at 12 United States centers. Major adverse cardiac event (MACE) was defined as the composite of cardiac death, acute coronary syndrome, and target-vessel revascularization.

Results: IVUS was used in 344 procedures (37%) for stent optimization. Mean patient age was 65 ± 10 years and 83% were men. Patients in the IVUS group were less likely to have a prior myocardial infarction (39% vs 50%; P<.01), more likely to undergo right coronary artery CTO-PCI (49% vs 55%; P=.01), and had higher mean J-CTO score (2.6 ± 1.1 vs 2.4 ± 1.2; P=.04). The final crossing strategy in patients in the IVUS group was less likely to be antegrade wire escalation (54% vs 57%) and more likely to be retrograde (29% vs 21%; P<.01). Median follow-up was 141 days (interquartile range, 30-365 days). The incidence of 12-month MACE was similar in the IVUS and no-IVUS groups (20.3% vs 18.3%; log-rank P=.67).

Conclusion: IVUS was used for stent optimization in approximately one-third of CTO-PCIs. Despite higher lesion complexity in the IVUS group, the incidence of MACE was similar during follow-up.
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October 2020

A Boosted Ensemble Algorithm for Determination of Plaque Stability in High-Risk Patients on Coronary CTA.

JACC Cardiovasc Imaging 2020 10 15;13(10):2162-2173. Epub 2020 Jul 15.

Integrative Cardiovascular Imaging Research Center, Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea.

Objectives: This study sought to identify culprit lesion (CL) precursors among acute coronary syndrome (ACS) patients based on qualitative and quantitative computed tomography-based plaque characteristics.

Background: Coronary computed tomography angiography (CTA) has been validated for patient-level prediction of ACS. However, the applicability of coronary CTA to CL assessment is not known.

Methods: Utilizing the ICONIC (Incident COroNary Syndromes Identified by Computed Tomography) study, a nested case-control study of 468 patients with baseline coronary CTA, the study included ACS patients with invasive coronary angiography-adjudicated CLs that could be aligned to CL precursors on baseline coronary CTA. Separate blinded core laboratories adjudicated CLs and performed atherosclerotic plaque evaluation. Thereafter, the study used a boosted ensemble algorithm (XGBoost) to develop a predictive model of CLs. Data were randomly split into a training set (80%) and a test set (20%). The area under the receiver-operating characteristic curve of this model was compared with that of diameter stenosis (model 1), high-risk plaque features (model 2), and lesion-level features of CL precursors from the ICONIC study (model 3). Thereafter, the machine learning (ML) model was applied to 234 non-ACS patients with 864 lesions to determine model performance for CL exclusion.

Results: CL precursors were identified by both coronary angiography and baseline coronary CTA in 124 of 234 (53.0%) patients, with a total of 582 lesions (containing 124 CLs) included in the analysis. The ML model demonstrated significantly higher area under the receiver-operating characteristic curve for discriminating CL precursors (0.774; 95% confidence interval [CI]: 0.758 to 0.790) compared with model 1 (0.599; 95% CI: 0.599 to 0.599; p < 0.01), model 2 (0.532; 95% CI: 0.501 to 0.563; p < 0.01), and model 3 (0.672; 95% CI: 0.662 to 0.682; p < 0.01). When applied to the non-ACS cohort, the ML model had a specificity of 89.3% for excluding CLs.

Conclusions: In a high-risk cohort, a boosted ensemble algorithm can be used to predict CL from non-CL precursors on coronary CTA.
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http://dx.doi.org/10.1016/j.jcmg.2020.03.025DOI Listing
October 2020

Quantitative assessment of coronary plaque volume change related to triglyceride glucose index: The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry.

Cardiovasc Diabetol 2020 07 18;19(1):113. Epub 2020 Jul 18.

Department of Imaging and Medicine, Cedars Sinai Medical Center, Los Angeles, CA, USA.

Background: The association between triglyceride glucose (TyG) index and coronary atherosclerotic change remains unclear. We aimed to evaluate the association between TyG index and coronary plaque progression (PP) using serial coronary computed tomography angiography (CCTA).

Methods: A total of 1143 subjects (aged 60.7 ± 9.3 years, 54.6% male) who underwent serial CCTA with available data on TyG index and diabetic status were analyzed from The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. PP was defined as plaque volume (PV) (mm) at follow-up minus PV at index > 0. Annual change of PV (mm/year) was defined as PV change divided by inter-scan period. Rapid PP was defined as the progression of percent atheroma volume (PV divided by vessel volume multiplied by 100) ≥ 1.0%/year.

Results: The median inter-scan period was 3.2 (range 2.6-4.4) years. All participants were stratified into three groups based on TyG index tertiles. The overall incidence of PP was 77.3%. Baseline total PV (group I [lowest]: 30.8 (0.0-117.7), group II: 47.2 (6.2-160.4), and group III [highest]: 57.5 (8.4-154.3); P < 0.001) and the annual change of total PV (group I: 5.7 (0.0-20.2), group II: 7.6 (0.5-23.5), and group III: 9.4 (1.4-27.7); P = 0.010) were different among all groups. The risk of PP (odds ratio [OR] 1.648; 95% confidence interval [CI] 1.167-2.327; P = 0.005) and rapid PP (OR 1.777; 95% CI 1.288-2.451; P < 0.001) was increased in group III compared to that in group I. TyG index had a positive and significant association with an increased risk of PP and rapid PP after adjusting for confounding factors.

Conclusion: TyG index is an independent predictive marker for the progression of coronary atherosclerosis. Clinical registration ClinicalTrials.gov NCT02803411.
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http://dx.doi.org/10.1186/s12933-020-01081-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368987PMC
July 2020

Intensive Training and Real-Time Quality Control by a Physiology Core Laboratory: Lessons From DEFINE-PCI.

Circ Cardiovasc Interv 2020 07 2;13(7):e009077. Epub 2020 Jul 2.

Clinical Trials Center, Cardiovascular Research Foundation, New York, NY (M.M., A.M., Z.A.A., G.W.S., A.J.).

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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.009077DOI Listing
July 2020

A single healthcare experience with Impella RP.

Catheter Cardiovasc Interv 2021 Jan 22;97(1):E161-E167. Epub 2020 Jun 22.

Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

Objectives: To understand the predictors of survival and indications for Impella RP in a single healthcare experience.

Background: The Impella RP can be used to temporarily support patients with right ventricular (RV) dysfunction after left ventricular assist device (LVAD) placement or myocardial infarction (MI). However, recent postmarket approval data have raised concerns of higher than expected mortality with this device.

Methods: A retrospective chart review and analysis of all patients that underwent Impella RP placement in the Emory Healthcare system between January 2016 and December 2018 were performed. Patients were classified according to the indication.

Results: A total of 39 patients underwent Impella RP placement. Six patients were post-LVAD, 9 were implanted for massive pulmonary embolism with persistent shock, 8 for postcardiac surgery RV failure (non-LVAD), 11 for RV failure post-MI, and 5 for new or worsening nonischemic cardiomyopathy. The worst survival was noted in MI-related cardiogenic shock group and in patients who presented with cardiac arrest (3/12). All observed deaths were due to persistent refractory shock. There was no device related death. Survival improved during the last year of experience compared to the first 2 years.

Conclusion: This study supports the selective use of the Impella RP, with a higher than national reported survival rate (49% vs. 28.6%). Indication appears to be an important factor determining survival.
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http://dx.doi.org/10.1002/ccd.28986DOI Listing
January 2021

Impact of Successful Chronic Total Occlusion Percutaneous Coronary Interventions on Subsequent Clinical Outcomes.

J Invasive Cardiol 2020 Nov 22;32(11):433-439. Epub 2020 Jun 22.

Minneapolis Heart Institute, 920 E 28th Street #300, Minneapolis, Minnesota 55407 USA.

Background: The impact of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) on angina and subsequent incidence of major adverse cardiovascular event (MACE) rate remains controversial.

Methods: We compared patient- reported angina change and the incidence of MACE (defined as death, myocardial infarction [MI], target-vessel revascularization) between successful vs failed CTO-PCI in 1612 patients participating in a large, multicenter registry.

Results: CTO-PCI was successful in 1387 patients (86%). Compared with failed CTO-PCI, successful CTO-PCI patients were less likely to have history of heart failure (33% vs 41%; P=.02), prior MI (49% vs 62%; P<.01), or prior coronary revascularization (63% vs 71% [P=.03] for PCI and 30% vs 40% [P<.01] for coronary artery bypass graft surgery). Patients in the successful CTO-PCI group had lower J-CTO scores (2.4 ± 1.3 vs 3.1 ± 1.1; P<.01) and lower PROGRESS-CTO Complications scores (1.1 ± 1.0 vs 1.6 ± 1.0; P<.01). After a mean follow-up of 181 ± 153 days, patients with successful PCI were more likely to have angina improvement (83% vs 38%; P<.01) and had lower incidence of 1-year MACE (8% vs 15%; P<.01), death (3% vs 7%; P<.01), and MI (2% vs 4%; P=.02). On multivariable analysis, however, CTO-PCI success was not independently associated with MACE.

Conclusion: Compared with failed CTO-PCI, successful CTO-PCI is associated with better angina improvement and lower incidence of MACE (on univariable analysis) during follow-up.
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November 2020