Development and Validation of a Quantitative Coronary CT Angiography Model for Diagnosis of Vessel-Specific Coronary Ischemia.

BACKGROUND: Noninvasive stress testing is commonly used for detection of coronary ischemia but possesses variable accuracy and may result in excessive health care costs. OBJECTIVES: This study aimed to derive and validate an artificial intelligence-guided quantitative coronary computed tomography angiography (AI-QCT) model for the diagnosis of coronary ischemia that integrates atherosclerosis and vascular morphology measures (AI-QCTISCHEMIA) and to evaluate its prognostic utility for major adverse cardiovascular events (MACE). METHODS: A post hoc analysis of the CREDENCE (Computed Tomographic Evaluation of Atherosclerotic Determinants of Myocardial Ischemia) and PACIFIC-1 (Comparison of Coronary Computed Tomography Angiography, Single Photon Emission Computed Tomography [SPECT], Positron Emission Tomography [PET], and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve) studies was performed. In both studies, symptomatic patients with suspected stable coronary artery disease had prospectively undergone coronary computed tomography angiography (CTA), myocardial perfusion imaging (MPI), SPECT, or PET, fractional flow reserve by CT (FFRCT), and invasive coronary angiography in conjunction with invasive FFR measurements. The AI-QCTISCHEMIA model was developed in the derivation cohort of the CREDENCE study, and its diagnostic performance for coronary ischemia (FFR ≤0.80) was evaluated in the CREDENCE validation cohort and PACIFIC-1. Its prognostic value was investigated in PACIFIC-1. RESULTS: In CREDENCE validation (n = 305, age 64.4 ± 9.8 years, 210 [69%] male), the diagnostic performance by area under the receiver-operating characteristics curve (AUC) on per-patient level was 0.80 (95% CI: 0.75-0.85) for AI-QCTISCHEMIA, 0.69 (95% CI: 0.63-0.74; P < 0.001) for FFRCT, and 0.65 (95% CI: 0.59-0.71; P < 0.001) for MPI. In PACIFIC-1 (n = 208, age 58.1 ± 8.7 years, 132 [63%] male), the AUCs were 0.85 (95% CI: 0.79-0.91) for AI-QCTISCHEMIA, 0.78 (95% CI: 0.72-0.84; P = 0.037) for FFRCT, 0.89 (95% CI: 0.84-0.93; P = 0.262) for PET, and 0.72 (95% CI: 0.67-0.78; P < 0.001) for SPECT. Adjusted for clinical risk factors and coronary CTA-determined obstructive stenosis, a positive AI-QCTISCHEMIA test was associated with an HR of 7.6 (95% CI: 1.2-47.0; P = 0.030) for MACE. CONCLUSIONS: This newly developed coronary CTA-based ischemia model using coronary atherosclerosis and vascular morphology characteristics accurately diagnoses coronary ischemia by invasive FFR and provides robust prognostic utility for MACE beyond presence of stenosis.

Rationale and design of the CONFIRM2 (Quantitative COroNary CT Angiography Evaluation For Evaluation of Clinical Outcomes: An InteRnational, Multicenter Registry) study.

BACKGROUND: In the last 15 years, large registries and several randomized clinical trials have demonstrated the diagnostic and prognostic value of coronary computed tomography angiography (CCTA). Advances in CT scanner technology and developments of analytic tools now enable accurate quantification of coronary artery disease (CAD), including total coronary plaque volume and low attenuation plaque volume. The primary aim of CONFIRM2, (Quantitative COroNary CT Angiography Evaluation For Evaluation of Clinical Outcomes: An InteRnational, Multicenter Registry) is to perform comprehensive quantification of CCTA findings, including coronary, non-coronary cardiac, non-cardiac vascular, non-cardiac findings, and relate them to clinical variables and cardiovascular clinical outcomes. DESIGN: CONFIRM2 is a multicenter, international observational cohort study designed to evaluate multidimensional associations between quantitative phenotype of cardiovascular disease and future adverse clinical outcomes in subjects undergoing clinically indicated CCTA. The targeted population is heterogenous and includes patients undergoing CCTA for atherosclerotic evaluation, valvular heart disease, congenital heart disease or pre-procedural evaluation. Automated software will be utilized for quantification of coronary plaque, stenosis, vascular morphology and cardiac structures for rapid and reproducible tissue characterization. Up to 30,000 patients will be included from up to 50 international multi-continental clinical CCTA sites and followed for 3-4 years. SUMMARY: CONFIRM2 is one of the largest CCTA studies to establish the clinical value of a multiparametric approach to quantify the phenotype of cardiovascular disease by CCTA using automated imaging solutions.

Determination of lipid-rich plaques by artificial intelligence-enabled quantitative computed tomography using near-infrared spectroscopy as reference.

BACKGROUND AND AIMS: Artificial intelligence quantitative CT (AI-QCT) determines coronary plaque morphology with high efficiency and accuracy. Yet, its performance to quantify lipid-rich plaque remains unclear. This study investigated the performance of AI-QCT for the detection of low-density noncalcified plaque (LD-NCP) using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). METHODS: The INVICTUS Registry is a multi-center registry enrolling patients undergoing clinically indicated coronary CT angiography and IVUS, NIRS-IVUS, or optical coherence tomography. We assessed the performance of various Hounsfield unit (HU) and volume thresholds of LD-NCP using maxLCBI4mm ≥ 400 as the reference standard and the correlation of the vessel area, lumen area, plaque burden, and lesion length between AI-QCT and IVUS. RESULTS: This study included 133 atherosclerotic plaques from 47 patients who underwent coronary CT angiography and NIRS-IVUS The area under the curve of LD-NCP<30HU was 0.97 (95% confidence interval [CI]: 0.93-1.00] with an optimal volume threshold of 2.30 mm3. Accuracy, sensitivity, and specificity were 94% (95% CI: 88-96%], 93% (95% CI: 76-98%), and 94% (95% CI: 88-98%), respectively, using <30 HU and 2.3 mm3, versus 42%, 100%, and 27% using <30 HU and >0 mm3 volume of LD-NCP (p < 0.001 for accuracy and specificity). AI-QCT strongly correlated with IVUS measurements; vessel area (r2 = 0.87), lumen area (r2 = 0.87), plaque burden (r2 = 0.78) and lesion length (r2 = 0.88), respectively. CONCLUSIONS: AI-QCT demonstrated excellent diagnostic performance in detecting significant LD-NCP using maxLCBI4mm ≥ 400 as the reference standard. Additionally, vessel area, lumen area, plaque burden, and lesion length derived from AI-QCT strongly correlated with respective IVUS measurements.

Rationale and design of the INVICTUS Registry: (Multicenter Registry of Invasive and Non-Invasive imaging modalities to compare Coronary Computed Tomography Angiography, Intravascular Ultrasound and Optical Coherence Tomography for the determination of Severity, Volume and Type of coronary atherosclerosiS).

BACKGROUND: Coronary CT angiography (CCTA) is a first-line noninvasive imaging modality for evaluating coronary artery disease (CAD). Recent advances in CCTA technology enabled semi-automated detection of coronary arteries and atherosclerosis. However, there have been to date no large-scale validation studies of automated assessment of coronary atherosclerosis phenotype and coronary artery dimensions by artificial intelligence (AI) compared to current standard invasive imaging. METHODS: INVICTUS registry is a multicenter, retrospective, and prospective study designed to evaluate the dimensions of coronary arteries, as well as the characteristic, volume, and phenotype of coronary atherosclerosis by CCTA, compared with the invasive imaging modalities including intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS)-IVUS and optical coherence tomography (OCT). All patients clinically underwent both CCTA and invasive imaging modalities within three months. RESULTS: Patients data are sent to the core-laboratories to analyze for stenosis severity, plaque characteristics and volume. The variables for CCTA are measured using an AI-based automated software and assessed independently with the variables measured at the imaging core laboratories for IVUS, NIRS-IVUS, and OCT in a blind fashion. CONCLUSION: The INVICTUS registry will provide new insights into the diagnostic value of CCTA for determining coronary atherosclerosis phenotype and coronary artery dimensions compared to IVUS, NIRS-IVUS, and OCT. Our findings will potentially shed new light on precision medicine informed by an AI-based coronary CTA assessment of coronary atherosclerosis burden, composition, and severity. (ClinicalTrials.gov: NCT04066062).

Impact of visceral fat on coronary artery disease as defined by quantitative computed tomography angiography.

OBJECTIVE: Obesity is associated with all-cause mortality and cardiovascular disease (CVD). Visceral fat (VF) is an important CVD risk metric given its independent correlation with myocardial infarction and stroke. This study aims to clarify the relationship between the presence and severity of VF with the presence and severity of coronary artery plaque. METHODS: In 145 consecutive asymptomatic patients, atherosclerosis imaging-quantitative computed tomography was performed for total plaque volume (TPV) and percentage atheroma volume, as well as the volume of noncalcified plaque (NCP), calcified plaque, and low-density NCP (LD-NCP), diameter stenosis, and vascular remodeling. This study also included VF analysis and subcutaneous fat analysis, recording of outer waist circumference, and percentage body fat analysis. RESULTS: The mean age of the patients was 56.1 [SD 8.5] years, and 84.0% were male. Measures of visceral adiposity (mean [SD, Q1-Q3 thresholds]) included estimated body fat, 28.7% (9.0%, 24.1%-33.0%); VF, 169.8 cm2 (92.3, 102.0-219.0 cm2 ); and subcutaneous fat, 223.6 mm2 (114.2, 142.5-288.0 mm2 ). The Spearman correlation coefficients of VF and plaque volume included TPV 0.22 (p = 0.0074), calcified plaque 0.12 (p = 0.62), NCP 0.25 (p = 0.0023), and LD-NCP 0.37 (p < 0.0001). There was a progression of the median coronary plaque volume for each quartile of VF including TPV (Q1: 19.8, Q2: 48.1, Q3: 86.4, and Q4: 136.6 mm3 [p = 0.0098]), NCP (Q1: 15.7, Q2: 35.4, Q3: 86.4, and Q4: 136.6 mm3 [p = 0.0032]), and LD-NCP (Q1: 0.6, Q2: 0.81, Q3: 2.0, and Q4: 5.0 mm3 [p < 0.0001]). CONCLUSIONS: These findings demonstrate progression with regard to VF and TPV, NCP volume, and LD-NCP volume. Notably, there was a progression of VF and amount of LD-NCP, which is known to be high risk for future cardiovascular events. A consistent progression may indicate the future utility of VF in CVD risk stratification.

Relation of Gender to Atherosclerotic Plaque Characteristics by Differing Angiographic Stenosis Severity.

It is unknown whether gender influences the atherosclerotic plaque characteristics (APCs) of lesions of varying angiographic stenosis severity. This study evaluated the imaging data of 303 symptomatic patients from the derivation arm of the CREDENCE (Computed TomogRaphic Evaluation of Atherosclerotic Determinants of Myocardial IsChEmia) trial, all of whom underwent coronary computed tomographic angiography and clinically indicated nonemergent invasive coronary angiography upon study enrollment. Index tests were interpreted by 2 blinded core laboratories, one of which performed quantitative coronary computed tomographic angiography using an artificial intelligence application to characterize and quantify APCs, including percent atheroma volume (PAV), low-density noncalcified plaque (LD-NCP), noncalcified plaque (NCP), calcified plaque (CP), lesion length, positive arterial remodeling, and high-risk plaque (a combination of LD-NCP and positive remodeling ≥1.10); the other classified lesions as obstructive (≥50% diameter stenosis) or nonobstructive (<50% diameter stenosis) based on quantitative invasive coronary angiography. The relation between APCs and angiographic stenosis was further examined by gender. The mean age of the study cohort was 64.4 ± 10.2 years (29.0% female). In patients with obstructive disease, men had more LD-NCP PAV (0.5 ± 0.4 vs 0.3 ± 0.8, p = 0.03) and women had more CP PAV (11.7 ± 1.6 vs 8.0 ± 0.8, p = 0.04). Obstructive lesions had more NCP PAV compared with their nonobstructive lesions in both genders, however, obstructive lesions in women also demonstrated greater LD-NCP PAV (0.4 ± 0.5 vs 1.0 ± 1.8, p = 0.03), and CP PAV (17.4 ± 16.5 vs 25.9 ± 18.7, p = 0.03) than nonobstructive lesions. Comparing the composition of obstructive lesions by gender, women had more CP PAV (26.3 ± 3.4 vs 15.8 ± 1.5, p = 0.005) whereas men had more NCP PAV (33.0 ± 1.6 vs 26.7 ± 2.5, p = 0.04). Men had more LD-NCP PAV in nonobstructive lesions compared with women (1.2 ± 0.2 vs 0.6 ± 0.2, p = 0.02). In conclusion, there are gender-specific differences in plaque composition based on stenosis severity.

Plaque Progression Differences Between Apixaban and Rivaroxaban in Patients With Atrial Fibrillation Measured With Cardiac Computed Tomography and Plaque Quantification.

BACKGROUND: Direct oral anticoagulants (DOACs) have been associated with less calcification and coronary plaque progression than warfarin. Whether different DOACs have different effects on coronary plaque burden and progression is not known. We compared the 12-month effects of apixaban and rivaroxaban on plaque characteristics and vascular morphology in patients with atrial fibrillation through quantitative cardiac computed tomographic angiography. STUDY QUESTION: In patients with nonvalvular atrial fibrillation using apixaban or rivaroxaban, are there differences in plaque quantification and progression measured with cardiac computed tomography? STUDY DESIGN: This is a post hoc analysis of 2 paired prospective, single-centered, randomized, open-label trials with blinded adjudication of results. In total, 74 patients were prospectively randomized in parallel trials: 29 to apixaban (2.5-5 mg BID) and 45 to rivaroxaban (20 mg QD). Serial cardiac computed tomographic angiography was performed at baseline and 52 weeks. MEASURES AND OUTCOMES: Comprehensive whole-heart analysis was performed for differences in the progression of percent atheroma volume (PAV), calcified plaque (CP) PAV, noncalcified plaque (NCP) PAV, positive arterial remodeling (PR) ≥1.10, and high-risk plaque (Cleerly Labs, New York, NY). RESULTS: Both groups had progression of all 3 plaque types (apixaban: CP 8.7 mm 3 , NCP 69.7 mm 3 , and LD-NCP 27.2 mm 3 ; rivaroxaban: CP 22.9 mm 3 , NCP 66.3 mm 3 , and LD-NCP 11.0 mm 3 ) and a total annual plaque PAV change (apixaban: PAV 1.5%, PAV-CP 0.12%, and PAV-NCP 0.92%; rivaroxaban: PAV 2.1%, PAV-CP 0.46%, and PAV-NCP 1.40%). There was significantly lower PAV-CP progression in the apixaban group compared with the rivaroxaban group (0.12% vs. 0.46% P = 0.02). High-risk plaque characteristics showed a significant change in PR of apixaban versus rivaroxaban ( P = 0.01). When the propensity score weighting model is applied, only PR changes are statistically significant ( P = 0.04). CONCLUSIONS: In both groups, there is progression of all types of plaque. There was a significant difference between apixaban and rivaroxaban on coronary calcification, with significantly lower calcific plaque progression in the apixaban group, and change in positive remodeling. With weighted modeling, only PR changes are statistically significant between the 2 DOACs.

Atherosclerosis Imaging Quantitative Computed Tomography (AI-QCT) to guide referral to invasive coronary angiography in the randomized controlled CONSERVE trial.

AIMS: We compared diagnostic performance, costs, and association with major adverse cardiovascular events (MACE) of clinical coronary computed tomography angiography (CCTA) interpretation versus semiautomated approach that use artificial intelligence and machine learning for atherosclerosis imaging-quantitative computed tomography (AI-QCT) for patients being referred for nonemergent invasive coronary angiography (ICA). METHODS: CCTA data from individuals enrolled into the randomized controlled Computed Tomographic Angiography for Selective Cardiac Catheterization trial for an American College of Cardiology (ACC)/American Heart Association (AHA) guideline indication for ICA were analyzed. Site interpretation of CCTAs were compared to those analyzed by a cloud-based software (Cleerly, Inc.) that performs AI-QCT for stenosis determination, coronary vascular measurements and quantification and characterization of atherosclerotic plaque. CCTA interpretation and AI-QCT guided findings were related to MACE at 1-year follow-up. RESULTS: Seven hundred forty-seven stable patients (60 ± 12.2 years, 49% women) were included. Using AI-QCT, 9% of patients had no CAD compared with 34% for clinical CCTA interpretation. Application of AI-QCT to identify obstructive coronary stenosis at the ≥50% and ≥70% threshold would have reduced ICA by 87% and 95%, respectively. Clinical outcomes for patients without AI-QCT-identified obstructive stenosis was excellent; for 78% of patients with maximum stenosis < 50%, no cardiovascular death or acute myocardial infarction occurred. When applying an AI-QCT referral management approach to avoid ICA in patients with <50% or <70% stenosis, overall costs were reduced by 26% and 34%, respectively. CONCLUSIONS: In stable patients referred for ACC/AHA guideline-indicated nonemergent ICA, application of artificial intelligence and machine learning for AI-QCT can significantly reduce ICA rates and costs with no change in 1-year MACE.

Diabetes, Atherosclerosis, and Stenosis by AI.

OBJECTIVE: This study evaluates the relationship between atherosclerotic plaque characteristics (APCs) and angiographic stenosis severity in patients with and without diabetes. Whether APCs differ based on lesion severity and diabetes status is unknown. RESEARCH DESIGN AND METHODS: We retrospectively evaluated 303 subjects from the Computed TomogRaphic Evaluation of Atherosclerotic Determinants of Myocardial IsChEmia (CREDENCE) trial referred for invasive coronary angiography with coronary computed tomographic angiography (CCTA) and classified lesions as obstructive (≥50% stenosed) or nonobstructive using blinded core laboratory analysis of quantitative coronary angiography. CCTA quantified APCs, including plaque volume (PV), calcified plaque (CP), noncalcified plaque (NCP), low-density NCP (LD-NCP), lesion length, positive remodeling (PR), high-risk plaque (HRP), and percentage of atheroma volume (PAV; PV normalized for vessel volume). The relationship between APCs, stenosis severity, and diabetes status was assessed. RESULTS: Among the 303 patients, 95 (31.4%) had diabetes. There were 117 lesions in the cohort with diabetes, 58.1% of which were obstructive. Patients with diabetes had greater plaque burden (P = 0.004). Patients with diabetes and nonobstructive disease had greater PV (P = 0.02), PAV (P = 0.02), NCP (P = 0.03), PAV NCP (P = 0.02), diseased vessels (P = 0.03), and maximum stenosis (P = 0.02) than patients without diabetes with nonobstructive disease. APCs were similar between patients with diabetes with nonobstructive disease and patients without diabetes with obstructive disease. Diabetes status did not affect HRP or PR. Patients with diabetes had similar APCs in obstructive and nonobstructive lesions. CONCLUSIONS: Patients with diabetes and nonobstructive stenosis had an association to similar APCs as patients without diabetes who had obstructive stenosis. Among patients with nonobstructive disease, patients with diabetes had more total PV and NCP.

High Dose "HDR-Like" Prostate SBRT: PSA 10-Year Results From a Mature, Multi-Institutional Clinical Trial.

Purpose/Objectives: Although ample intermediate-term prostate stereotactic body radiotherapy (SBRT) outcomes have been reported, 10-year results remain relatively sparse. Materials/Methods: Eighteen institutions enrolled 259 low- and intermediate-risk patients. Median follow-up is 5.5 years, with 66 patients followed ≥ 10 years. This SBRT regimen specifically emulated an existing HDR brachytherapy dose schedule and isodose morphology, prescribed to 38 Gy/4 fractions, delivered daily by robotic SBRT, mandating > 150% dose escalation in the peripheral zone. Androgen deprivation therapy was not allowed, and a hydrogel spacer was not available at that time. Results: Median pre-SBRT PSA 5.12 ng/mL decreased to 0.1 ng/mL by 3.5 years, with further decrease to a nadir of < 0.1 ng/mL by 7 years, maintained through 10 years. Ten-year freedom from biochemical recurrence measured 100% for low-risk, 84.3% for favorable intermediate risk (FIR), and 68.4% for unfavorable intermediate (UIR) cases. Multivariable analysis revealed that the UIR group bifurcated into two distinct prognostic subgroups. Those so classified by having Gleason score 4 + 3 and/or clinical stage T2 (versus T1b/T1c) had a significantly poorer 10 year freedom from biochemical recurrence rate, 54.8% if either or both factors were present, while UIR patients without these specific factors had a 94.4% 10-year freedom from biochemical recurrence rate. The cumulative incidence of grade 2 GU toxicity modestly increased over time - 16.3% at 5 years increased to 19.2% at 10 years-- while the incidence of grade 3+ GU and GI toxicity remained low and stable to 10 years - 2.6% and 0%, respectively. The grade 2 GI toxicity incidence also remained low and stable to 10 years - 4.1% with no further events after year 5. Conclusion: This HDR-like SBRT regimen prescribing 38 Gy/4 fractions but delivering much higher intraprostatic doses on a daily basis is safe and effective. This treatment achieves a median PSA nadir of <0.1 ng/mL and provides high long-term disease control rates without ADT except for a subgroup of unfavorable intermediate-risk patients.

Interobserver variability among expert readers quantifying plaque volume and plaque characteristics on coronary CT angiography: a CLARIFY trial sub-study.

BACKGROUND: The difference between expert level (L3) reader and artificial intelligence (AI) performance for quantifying coronary plaque and plaque components is unknown. OBJECTIVE: This study evaluates the interobserver variability among expert readers for quantifying the volume of coronary plaque and plaque components on coronary computed tomographic angiography (CCTA) using an artificial intelligence enabled quantitative CCTA analysis software as a reference (AI-QCT). METHODS: This study uses CCTA imaging obtained from 232 patients enrolled in the CLARIFY (CT EvaLuation by ARtificial Intelligence For Atherosclerosis, Stenosis and Vascular MorphologY) study. Readers quantified overall plaque volume and the % breakdown of noncalcified plaque (NCP) and calcified plaque (CP) on a per vessel basis. Readers categorized high risk plaque (HRP) based on the presence of low-attenuation-noncalcified plaque (LA-NCP) and positive remodeling (PR; ≥1.10). All CCTAs were analyzed by an FDA-cleared software service that performs AI-driven plaque characterization and quantification (AI-QCT) for comparison to L3 readers. Reader generated analyses were compared among readers and to AI-QCT generated analyses. RESULTS: When evaluating plaque volume on a per vessel basis, expert readers achieved moderate to high interobserver consistency with an intra-class correlation coefficient of 0.78 for a single reader score and 0.91 for mean scores. There was a moderate trend between readers 1, 2, and 3 and AI with spearman coefficients of 0.70, 0.68 and 0.74, respectively. There was high discordance between readers and AI plaque component analyses. When quantifying %NCP v. %CP, readers 1, 2, and 3 achieved a weighted kappa coefficient of 0.23, 0.34 and 0.24, respectively, compared to AI with a spearman coefficient of 0.38, 0.51, and 0.60, respectively. The intra-class correlation coefficient among readers for plaque composition assessment was 0.68. With respect to HRP, readers 1, 2, and 3 achieved a weighted kappa coefficient of 0.22, 0.26, and 0.17, respectively, and a spearman coefficient of 0.36, 0.35, and 0.44, respectively. CONCLUSION: Expert readers performed moderately well quantifying total plaque volumes with high consistency. However, there was both significant interobserver variability and high discordance with AI-QCT when quantifying plaque composition.

Quantitative plaque analysis with A.I.-augmented CCTA in end-stage renal disease and complex CAD.

BACKGROUND: Adverse cardiovascular events are a significant cause of mortality in end-stage renal disease (ESRD) patients. High-risk plaque anatomy may be a significant contributor. However, their atherosclerotic phenotypes have not been described. We sought to define atherosclerotic plaque characteristics (APC) in dialysis patients using artificial-intelligence augmented CCTA. METHODS: We retrospectively analyzed ESRD patients referred for CCTA using an FDA approved artificial-intelligence augmented-CCTA program (Cleerly). Coronary lesions were evaluated for APCs by CCTA. APCs included percent atheroma volume(PAV), low-density non-calcified-plaque (LD-NCP), non-calcified-plaque (NCP), calcified-plaque (CP), length, and high-risk-plaque (HRP), defined by LD-NCP and positive arterial remodeling >1.10 (PR). RESULTS: 79 ESRD patients were enrolled, mean age 65.3 years, 32.9% female. Disease distribution was non-obstructive (65.8%), 1-vessel disease (21.5%), 2-vessel disease (7.6%), and 3-vessel disease (5.1%). Mean total plaque volume (TPV) was 810.0 mm3, LD-NCP 16.8 mm3, NCP 403.1 mm3, and CP 390.1 mm3. HRP was present in 81.0% patients. Patients with at least one >50% stenosis, or obstructive lesions, had significantly higher TPV, LD-NCP, NCP, and CP. Patients >65 years had more CP and higher PAV. CONCLUSION: Our study provides novel insight into ESRD plaque phenotypes and demonstrates that artificial-intelligence augmented CCTA analysis is feasible for CAD characterization despite severe calcification. We demonstrate elevated plaque burden and stenosis caused by predominantly non-calcified-plaque. Furthermore, the quantity of calcified-plaques increased with age, with men exhibiting increased number of 2-feature plaques and higher plaque volumes. Artificial-intelligence augmented CCTA analysis of APCs may be a promising metric for cardiac risk stratification and warrants further prospective investigation.

Coronary CTA With AI-QCT Interpretation: Comparison With Myocardial Perfusion Imaging for Detection of Obstructive Stenosis Using Invasive Angiography as Reference Standard.

BACKGROUND. Deep learning frameworks have been applied to interpretation of coronary CTA performed for coronary artery disease (CAD) evaluation. OBJECTIVE. The purpose of our study was to compare the diagnostic performance of myocardial perfusion imaging (MPI) and coronary CTA with artificial intelligence quantitative CT (AI-QCT) interpretation for detection of obstructive CAD on invasive angiography and to assess the downstream impact of including coronary CTA with AI-QCT in diagnostic algorithms. METHODS. This study entailed a retrospective post hoc analysis of the derivation cohort of the prospective 23-center Computed Tomographic Evaluation of Atherosclerotic Determinants of Myocardial Ischemia (CREDENCE) trial. The study included 301 patients (88 women and 213 men; mean age, 64.4 ± 10.2 [SD] years) recruited from May 2014 to May 2017 with stable symptoms of myocardial ischemia referred for nonemergent invasive angiography. Patients underwent coronary CTA and MPI before angiography with quantitative coronary angiography (QCA) measurements and fractional flow reserve (FFR). CTA examinations were analyzed using an FDA-cleared cloud-based software platform that performs AI-QCT for stenosis determination. Diagnostic performance was evaluated. Diagnostic algorithms were compared. RESULTS. Among 102 patients with no ischemia on MPI, AI-QCT identified obstructive (≥ 50%) stenosis in 54% of patients, including severe (≥ 70%) stenosis in 20%. Among 199 patients with ischemia on MPI, AI-QCT identified nonobstructive (1-49%) stenosis in 23%. AI-QCT had significantly higher AUC (all p < .001) than MPI for predicting ≥ 50% stenosis by QCA (0.88 vs 0.66), ≥ 70% stenosis by QCA (0.92 vs 0.81), and FFR < 0.80 (0.90 vs 0.71). An AI-QCT result of ≥ 50% stenosis and ischemia on stress MPI had sensitivity of 95% versus 74% and specificity of 63% versus 43% for detecting ≥ 50% stenosis by QCA measurement. Compared with performing MPI in all patients and those showing ischemia undergoing invasive angiography, a scenario of performing coronary CTA with AIQCT in all patients and those showing ≥ 70% stenosis undergoing invasive angiography would reduce invasive angiography utilization by 39%; a scenario of performing MPI in all patients and those showing ischemia undergoing coronary CTA with AI-QCT and those with ≥ 70% stenosis on AI-QCT undergoing invasive angiography would reduce invasive angiography utilization by 49%. CONCLUSION. Coronary CTA with AI-QCT had higher diagnostic performance than MPI for detecting obstructive CAD. CLINICAL IMPACT. A diagnostic algorithm incorporating AI-QCT could substantially reduce unnecessary downstream invasive testing and costs. TRIAL REGISTRATION. Clinicaltrials.gov NCT02173275.

Coronary CTA plaque volume severity stages according to invasive coronary angiography and FFR.

BACKGROUND: Atherosclerotic plaque characterization by coronary computed tomography angiography (CCTA) enables quantification of coronary artery disease (CAD) burden and type, which has been demonstrated as the strongest discriminant of future risk of major adverse cardiac events (MACE). To date, there are no clinically useful thresholds to assist with understanding a patient's disease burden and guide diagnosis and management, as there exists with coronary artery calcium (CAC) scoring. The purpose of this manuscript is to establish clinically relevant plaque stages and thresholds based on evidence from invasive angiographic stenosis (ICA) and fractional flow reserve (FFR) data. METHODS: 303 patients underwent CCTA prior to ICA and FFR for an AHA/ACC clinical indication. Quantitative computed tomography (QCT) was performed for total plaque volume (TPV, mm3) and percent atheroma volume (PAV, %). We segmented atherosclerosis by composition for low-density non-calcified plaque (LD-NCP), non-calcified plaque (NCP), and calcified plaque (CP). ICAs were evaluated by quantitative coronary angiography (QCA) for all coronary segments for % diameter stenosis. The relationship of atherosclerotic plaque burden and composition by QCT to ICA stenosis extent and severity by QCA and presence of ischemia by FFR was assessed to develop 4 distinct disease stages. RESULTS: The mean age of the patients was 64.4 â€‹± â€‹10.2 years; 71% male. At the 50% QCA stenosis threshold, QCT revealed a mean PAV of 9.7 (±8.2)% and TPV of 436 (±444.9)mm3 for those with non-obstructive CAD; PAV of 11.7 (±8.0)% and TPV of 549.3 (±408.3) mm3 for 1 vessel disease (1VD), PAV of 17.8 (±9.8)% and TPV of 838.9 (±550.7) mm3 for 2VD, and PAV of 19.2 (±8.2)% and TPV of 799.9 (±357.4) mm3 for 3VD/left main disease (LMD). Non-ischemic patients (FFR >0.8) had a mean PAV of 9.2 (±7.3) % and TPV of 422.9 (±387.9 â€‹mm3) while patients with at least one vessel ischemia (FFR ≤0.8) had a PAV of 15.2 (±9.5)% and TPV of 694.6 (±485.1). Definition of plaque stage thresholds of 0, 250, 750 â€‹mm3 and 0, 5, and 15% PAV resulted in 4 clinically distinct stages in which patients with no, nonobstructive, single VD and multi-vessel disease were optimally distributed. CONCLUSION: Atherosclerotic plaque burden by QCT is related to stenosis severity and extent as well as ischemia. We propose staging of CAD atherosclerotic plaque burden using the following definitions: Stage 0 (Normal, 0% PAV, 0 â€‹mm3 TPV), Stage 1 (Mild, >0-5% PAV or >0-250 â€‹mm3 TPV), Stage 2 (Moderate, >5-15% PAV or >250-750 â€‹mm3 TPV) and Stage 3 (Severe, >15% PAV or >750 mm3 TPV).

The effect of scan and patient parameters on the diagnostic performance of AI for detecting coronary stenosis on coronary CT angiography.

OBJECTIVES: To determine whether coronary computed tomography angiography (CCTA) scanning, scan preparation, contrast, and patient based parameters influence the diagnostic performance of an artificial intelligence (AI) based analysis software for identifying coronary lesions with ≥50% stenosis. BACKGROUND: CCTA is a noninvasive imaging modality that provides diagnostic and prognostic benefit to patients with coronary artery disease (CAD). The use of AI enabled quantitative CCTA (AI-QCT) analysis software enhances our diagnostic and prognostic ability, however, it is currently unclear whether software performance is influenced by CCTA scanning parameters. METHODS: CCTA and quantitative coronary CT (QCT) data from 303 stable patients (64 ± 10 years, 71% male) from the derivation arm of the CREDENCE Trial were retrospectively analyzed using an FDA-cleared cloud-based software that performs AI-enabled coronary segmentation, lumen and vessel wall determination, plaque quantification and characterization, and stenosis determination. The algorithm's diagnostic performance measures (sensitivity, specificity, and accuracy) for detecting coronary lesions of ≥50% stenosis were determined based on concordance with QCA measurements and subsequently compared across scanning parameters (including scanner vendor, model, single vs dual source, tube voltage, dose length product, gating technique, timing method), scan preparation technique (use of beta blocker, use and dose of nitroglycerin), contrast administration parameters (contrast type, infusion rate, iodine concentration, contrast volume) and patient parameters (heart rate and BMI). RESULTS: Within the patient cohort, 13% demonstrated ≥50% stenosis in 3 vessel territories, 21% in 2 vessel territories, 35% in 1 vessel territory while 32% had <50% stenosis in all vessel territories evaluated by QCA. Average AI analysis time was 10.3 ± 2.7 min. On a per vessel basis, there were significant differences only in sensitivity for ≥50% stenosis based on contrast type (iso-osmolar 70.0% vs non isoosmolar 92.1% p = 0.0345) and iodine concentration (<350 mg/ml 70.0%, 350-369 mg/ml 90.0%, 370-400 mg/ml 90.0%, >400 mg/ml 95.2%; p = 0.0287) in the context of low injection flow rates. On a per patient basis there were no significant differences in AI diagnostic performance measures across all measured scanner, scan technique, patient preparation, contrast, and individual patient parameters. CONCLUSION: The diagnostic performance of AI-QCT analysis software for detecting moderate to high grade stenosis are unaffected by commonly used CCTA scanning parameters and across a range of common scanning, scanner, contrast and patient variables. CONDENSED ABSTRACT: An AI-enabled quantitative CCTA (AI-QCT) analysis software has been validated as an effective tool for the identification, quantification and characterization of coronary plaque and stenosis through comparison to blinded expert readers and quantitative coronary angiography. However, it is unclear whether CCTA screening parameters related to scanner parameters, scan technique, contrast volume and rate, radiation dose, or a patient's BMI or heart rate at time of scan affect the software's diagnostic measures for detection of moderate to high grade stenosis. AI performance measures were unaffected across a broad range of commonly encountered scanner, patient preparation, scan technique, intravenous contrast and patient parameters.

Relationship of age, atherosclerosis and angiographic stenosis using artificial intelligence.

OBJECTIVE: The study evaluates the relationship of coronary stenosis, atherosclerotic plaque characteristics (APCs) and age using artificial intelligence enabled quantitative coronary computed tomographic angiography (AI-QCT). METHODS: This is a post-hoc analysis of data from 303 subjects enrolled in the CREDENCE (Computed TomogRaphic Evaluation of Atherosclerotic Determinants of Myocardial IsChEmia) trial who were referred for invasive coronary angiography and subsequently underwent coronary computed tomographic angiography (CCTA). In this study, a blinded core laboratory analysing quantitative coronary angiography images classified lesions as obstructive (≥50%) or non-obstructive (<50%) while AI software quantified APCs including plaque volume (PV), low-density non-calcified plaque (LD-NCP), non-calcified plaque (NCP), calcified plaque (CP), lesion length on a per-patient and per-lesion basis based on CCTA imaging. Plaque measurements were normalised for vessel volume and reported as % percent atheroma volume (%PAV) for all relevant plaque components. Data were subsequently stratified by age <65 and ≥65 years. RESULTS: The cohort was 64.4±10.2 years and 29% women. Overall, patients >65 had more PV and CP than patients <65. On a lesion level, patients >65 had more CP than younger patients in both obstructive (29.2 mm3 vs 48.2 mm3; p<0.04) and non-obstructive lesions (22.1 mm3 vs 49.4 mm3; p<0.004) while younger patients had more %PAV (LD-NCP) (1.5% vs 0.7%; p<0.038). Younger patients had more PV, LD-NCP, NCP and lesion lengths in obstructive compared with non-obstructive lesions. There were no differences observed between lesion types in older patients. CONCLUSION: AI-QCT identifies a unique APC signature that differs by age and degree of stenosis and provides a foundation for AI-guided age-based approaches to atherosclerosis identification, prevention and treatment.

Prostate SBRT: Comparison the Efficacy and Toxicity of Two Different Dose Fractionation Schedules.

Background: CyberKnife SBRT is capable of producing dosimetry comparable to that created by HDR brachytherapy. Our original CyberKnife prostate SBRT schedule of 3,800 cGy/4 fractions ("high dose") was based upon favorable published prostate HDR brachytherapy experience. Subsequently, our trial was modified to allow a lower dose of 3,400 cGy/5 fractions ("moderate dose") in selected cases. Methods: Two hundred eighty-nine low and intermediate-risk patients were treated to either high dose (178 pts) or moderate dose (111 pts). The dose selection was individualized; high dose more commonly used in younger, intermediate-risk patients, and moderate dose more commonly used in older, low-risk patients. Results: Median PSA reached 5-year nadir levels of 0.034 ng/mL in the high dose, vs. 0.1 ng/mL in the moderate dose groups, respectively (p = 0.044 by year 4), with 62 vs. 44% reaching an ablation PSA nadir (<0.1 ng/mL) by year 5, respectively. Five year biochemical relapse free survival rates measured 98.3% for moderate dose and 94.3% for high dose groups, respectively (p = 0.1946). Five-year actuarial grade 2 genitourinary (GU) toxicity rates measured 11.6 vs. 8.7% for high dose vs. moderate dose groups, respectively, with a far lower incidence of grade ≥3 GU and grade ≥2 GI toxicity rates in both groups. Conclusions: Both regimens are efficacious in their respective, selected groups. Both arms have low grade ≥3 GU toxicity and ≥grade 2 GI toxicity. In favor of the original high dose regimen, it has longer follow-up, produces a lower PSA nadir value and is more likely to eventually produce an ablation PSA nadir (<0.1 ng/mL). In favor of the lower dose regimen, it also produces a low PSA nadir, and does so with a slightly lower grade 2 GU toxicity rate. As a lower PSA nadir could be the initial predictor a lower clinical relapse rate far beyond 5 years, even if no difference is apparent within that time frame, a practical strategy could be to more strongly consider the high dose regimen in those with the greatest potential longevity, while for those with a more limited longevity, particularly if they have minimal negative prognostic factors, the moderate dose regimen could be more attractive.

Retreatment for Local Recurrence of Prostatic Carcinoma After Prior Therapeutic Irradiation: Efficacy and Toxicity of HDR-Like SBRT.

PURPOSE: We evaluated the use of high dose-rate-like stereotactic body radiation therapy (SBRT) retreatment for biopsy-proven local persistence in prostate postradiation therapy, evaluating efficacy and toxicity. METHODS AND MATERIALS: From 2009 to 2018, 50 patients with biopsy-proven recurrent prostate cancer >2 years after prior treatment were retreated with a high dose-rate-like dose of 3400 cGy over 5 fractions. Previous radiation therapy dose measured 75.6 Gy (64.8-81.0) and median salvage interval was 8.1 years (32-241 mo.). Eighty-three percent of patients had Gleason score 7 or higher disease at retreatment. Those with preexisting toxicity >grade 1 from their prior course were excluded. The planning target volume was comprised of the clinical target volume (prostate + any contiguous extension only) with no additional expansion. Toxicity assessment used CTCAE v.3.0 criteria. RESULTS: Median follow-up was 44 months (3-110). Median pre-SBRT salvage baseline prostate specific antigen (PSA) of 3.97 ng/mL decreased to 0.6 ng/mL and 0.16 ng/mL at 1 and 5 years in nonrelapsed patients, respectively. Actuarial 5-year biochemical disease-free survival (DFS) measured 60%, with corresponding 5-year actuarial local, distant, and salvage androgen deprivation therapy free rates of 94%, 89%, and 69%, respectively. Actuarial 5-year biochemical DFS measured 78% if PSA at salvage was <6.92 ng/mL versus 12% with ≥6.92 ng/mL (P = .0001). Toxicity was primarily in the GU domain, with an 8% 5-year actuarial rate of grade 3+, 3% when limited to salvage of "conventional external beam only" local relapse. No gastrointestinal (GI) toxicity >grade 1 occurred. Of the 30% sexually potent at the time of salvage, 82% subsequently lost potency. CONCLUSIONS: SBRT salvage of local prostate recurrence in previously irradiated patients appears clinically feasible in this challenging group. It demonstrates favorable PSA and DFS response, typically deferring the need for salvage androgen deprivation therapy or other treatment by over 5 years, with low GU and GI toxicity.

Phase 2 Multicenter Trial of Heterogeneous-dosing Stereotactic Body Radiotherapy for Low- and Intermediate-risk Prostate Cancer: 5-year Outcomes.

BACKGROUND: Stereotactic body radiation therapy is an emerging treatment for prostate cancer (PC), with potential biological and oncologic advantages. A well-established radiation dosing schedule (38Gy in 4 fractions) has shown excellent long-term efficacy in high-dose-rate (HDR) brachytherapy. OBJECTIVE: To report 5-yr efficacy, toxicity, and quality-of-life (QOL) outcomes of a novel 4-d SBRT regimen. DESIGN, SETTING, AND PARTICIPANTS: This was a single-arm prospective phase 2 trial involving 259 patients with low- or intermediate-risk PC treated at 18 US centers from December 2007 to February 2012. The median follow-up was 5yr (interquartile range 37-85mo). INTERVENTION: SBRT with 38Gy in four fractions; radiation plans mimicked HDR brachytherapy dosimetry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured freedom from biochemical recurrence (BCR) and assessed toxicities using the Common Terminology Criteria for Adverse Events v3.0 and QOL using the Expanded Prostate Cancer Index Composite. RESULTS AND LIMITATIONS: The 5-yr BCR-free rates were 100% and 88.5% for patients with low- and intermediate-risk PC, respectively. The cumulative 5-yr grade 2, 3, and 4 toxicity rates were 12.4%, 1.9%, and 0.4% for urinary, and 3.4%, 0%, and 0% for gastrointestinal toxicities, respectively. The median baseline prostate-specific antigen (PSA) level of 5.12ng/ml decreased to 0.1ng/ml by ≥42mo. QOL scores decreased at 1mo but returned to baseline by 6mo, with a later decline (≥24mo) in the urinary continence domain (pad use was 2% at baseline and 10% at 5yr), and lower sexual potency over time. Comparative outcomes versus other types of radiotherapy are difficult because the trial was not randomized. CONCLUSIONS: This regimen yields a high rate of BCR-free survival, with a very low median PSA nadir suggesting prostate ablation. For properly selected patients with low- or intermediate-risk PC who choose SBRT, this treatment regimen is effective. PATIENT SUMMARY: This potent four-treatment stereotactic body radiotherapy regimen appears to be effective for patients with early prostate cancer.