Artificial Intelligence-Enabled Quantitative Coronary Plaque and Hemodynamic Analysis for Predicting Acute Coronary Syndrome.

BACKGROUND: A lesion-level risk prediction for acute coronary syndrome (ACS) needs better characterization. OBJECTIVES: This study sought to investigate the additive value of artificial intelligence-enabled quantitative coronary plaque and hemodynamic analysis (AI-QCPHA). METHODS: Among ACS patients who underwent coronary computed tomography angiography (CTA) from 1 month to 3 years before the ACS event, culprit and nonculprit lesions on coronary CTA were adjudicated based on invasive coronary angiography. The primary endpoint was the predictability of the risk models for ACS culprit lesions. The reference model included the Coronary Artery Disease Reporting and Data System, a standardized classification for stenosis severity, and high-risk plaque, defined as lesions with ≥2 adverse plaque characteristics. The new prediction model was the reference model plus AI-QCPHA features, selected by hierarchical clustering and information gain in the derivation cohort. The model performance was assessed in the validation cohort. RESULTS: Among 351 patients (age: 65.9 ± 11.7 years) with 2,088 nonculprit and 363 culprit lesions, the median interval from coronary CTA to ACS event was 375 days (Q1-Q3: 95-645 days), and 223 patients (63.5%) presented with myocardial infarction. In the derivation cohort (n = 243), the best AI-QCPHA features were fractional flow reserve across the lesion, plaque burden, total plaque volume, low-attenuation plaque volume, and averaged percent total myocardial blood flow. The addition of AI-QCPHA features showed higher predictability than the reference model in the validation cohort (n = 108) (AUC: 0.84 vs 0.78; P < 0.001). The additive value of AI-QCPHA features was consistent across different timepoints from coronary CTA. CONCLUSIONS: AI-enabled plaque and hemodynamic quantification enhanced the predictability for ACS culprit lesions over the conventional coronary CTA analysis. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary Computed Tomography Angiography and Computational Fluid Dynamics II [EMERALD-II]; NCT03591328).

Impact of Smoking on Coronary Volume-to-Myocardial Mass Ratio: An ADVANCE Registry Substudy.

Purpose To examine the relationship between smoking status and coronary volume-to-myocardial mass ratio (V/M) among individuals with coronary artery disease (CAD) undergoing CT fractional flow reserve (CT-FFR) analysis. Materials and Methods In this secondary analysis, participants from the ADVANCE registry evaluated for suspected CAD from July 15, 2015, to October 20, 2017, who were found to have coronary stenosis of 30% or greater at coronary CT angiography (CCTA) were included if they had known smoking status and underwent CT-FFR and V/M analysis. CCTA images were segmented to calculate coronary volume and myocardial mass. V/M was compared between smoking groups, and predictors of low V/M were determined. Results The sample for analysis included 503 current smokers, 1060 former smokers, and 1311 never-smokers (2874 participants; 1906 male participants). After adjustment for demographic and clinical factors, former smokers had greater coronary volume than never-smokers (former smokers, 3021.7 mm3 ± 934.0 [SD]; never-smokers, 2967.6 mm3 ± 978.0; P = .002), while current smokers had increased myocardial mass compared with never-smokers (current smokers, 127.8 g ± 32.9; never-smokers, 118.0 g ± 32.5; P = .02). However, both current and former smokers had lower V/M than never-smokers (current smokers, 24.1 mm3/g ± 7.9; former smokers, 24.9 mm3/g ± 7.1; never-smokers, 25.8 mm3/g ± 7.4; P < .001 [unadjusted] and P = .002 [unadjusted], respectively). Current smoking status (odds ratio [OR], 0.74 [95% CI: 0.59, 0.93]; P = .009), former smoking status (OR, 0.81 [95% CI: 0.68, 0.97]; P = .02), stenosis of 50% or greater (OR, 0.62 [95% CI: 0.52, 0.74]; P < .001), and diabetes (OR, 0.67 [95% CI: 0.56, 0.82]; P < .001) were independent predictors of low V/M. Conclusion Both current and former smoking status were independently associated with low V/M. Keywords: CT Angiography, Cardiac, Heart, Ischemia/Infarction Clinical trial registration no. NCT02499679 Supplemental material is available for this article. © RSNA, 2024.

Prognostic Value of Coronary CT Angiography-derived Fractional Flow Reserve on 3-year Outcomes in Patients with Stable Angina.

Background The prognostic value of coronary CT angiography (CTA)-derived fractional flow reserve (FFR) beyond 1-year outcomes and in patients with high levels of coronary artery calcium (CAC) is uncertain. Purpose To assess the prognostic value of coronary CTA-derived FFR test results on 3-year clinical outcomes in patients with coronary stenosis and among a subgroup of patients with high levels of CAC. Materials and Methods This study represents a 3-year follow-up of patients with new-onset stable angina pectoris who were consecutively enrolled in the Assessing Diagnostic Value of Noninvasive CT-FFR in Coronary Care, known as ADVANCE (ClinicalTrials.gov: NCT02499679) registry, between December 2015 and October 2017 at three Danish sites. A high CAC was defined as an Agatston score of at least 400. A lesion-specific coronary CTA-derived FFR value of 2 cm with distal-to-stenosis value at or below 0.80 represented an abnormal test result. The primary end point was a composite of all-cause death and nonfatal spontaneous myocardial infarction. Event rates were estimated using the one-sample binomial model, and relative risk was compared between participants stratified by results of coronary CTA-derived FFR. Results This study included 900 participants: 523 participants with normal results (mean age, 64 years ± 9.6 [SD]; 318 male participants) and 377 with abnormal results from coronary CTA-derived FFR (mean age, 65 years ± 9.6; 264 male participants). The primary end point occurred in 11 of 523 (2.1%) and 25 of 377 (6.6%) participants with normal and abnormal coronary CTA-derived FFR results, respectively (relative risk, 3.1; 95% CI: 1.6, 6.3; P < .001). In participants with high CAC, the primary end point occurred in four of 182 (2.2%) and 19 of 212 (9.0%) participants with normal and abnormal coronary CTA-derived FFR results, respectively (relative risk, 4.1; 95% CI: 1.4, 11.8; P = .001). Conclusion In individuals with stable angina, a normal coronary CTA-derived FFR test result identified participants with a low 3-year risk of all-cause death or nonfatal spontaneous myocardial infarction, both in the overall cohort and in participants with high CAC scores. Clinical trial registration no. NCT02499679 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Sinitsyn in this issue.

Coronary Volume to Left Ventricular Mass Ratio in Patients With Hypertension.

The coronary vascular volume to left ventricular mass (V/M) ratio assessed by coronary computed tomography angiography (CCTA) is a promising new parameter to investigate the relation of coronary vasculature to the myocardium supplied. It is hypothesized that hypertension decreases the ratio between coronary volume and myocardial mass by way of myocardial hypertrophy, which could explain the detected abnormal myocardial perfusion reserve reported in patients with hypertension. Individuals enrolled in the multicenter ADVANCE (Assessing Diagnostic Value of Noninvasive FFRCT in Coronary Care) registry who underwent clinically indicated CCTA for analysis of suspected coronary artery disease with known hypertension status were included in current analysis. The V/M ratio was calculated from CCTA by segmenting the coronary artery luminal volume and left ventricular myocardial mass. In total, 2,378 subjects were included in this study, of whom 1,346 (56%) had hypertension. Left ventricular myocardial mass and coronary volume were higher in subjects with hypertension than normotensive patients (122.7 ± 32.8 g vs 120.0 ± 30.5 g, p = 0.039, and 3,105.0 ± 992.0 mm3 vs 2,965.6 ± 943.7 mm3, p <0.001, respectively). Subsequently, the V/M ratio was higher in patients with hypertension than those without (26.0 ± 7.6 mm3/g vs 25.3 ± 7.3 mm3/g, p = 0.024). After correcting for potential confounding factors, the coronary volume and ventricular mass remained higher in patients with hypertension (least square) mean difference estimate: 196.3 (95% confidence intervals [CI] 119.9 to 272.7) mm3, p <0.001, and 5.60 (95% CI 3.42 to 7.78) g, p <0.001, respectively), but the V/M ratio was not significantly different (least square mean difference estimate: 0.48 (95% CI -0.12 to 1.08) mm3/g, p = 0.116). In conclusion, our findings do not support the hypothesis that the abnormal perfusion reserve would be caused by reduced V/M ratio in patients with hypertension.

Influence of intensive lipid-lowering on CT derived fractional flow reserve in patients with stable chest pain: Rationale and design of the FLOWPROMOTE study.

INTRODUCTION: Coronary CT angiography (CTA) derived fractional flow reserve (FFRCT ) shows high diagnostic performance when compared to invasively measured FFR. Presence and extent of low attenuation plaque density have been shown to be associated with abnormal physiology by measured FFR. Moreover, it is well established that statin therapy reduces the rate of plaque progression and results in morphology alterations underlying atherosclerosis. However, the interplay between lipid lowering treatment, plaque regression, and the coronary physiology has not previously been investigated. AIM: To test whether lipid lowering therapy is associated with significant improvement in FFRCT , and whether there is a dose-response relationship between lipid lowering intensity, plaque regression, and coronary flow recovery. METHODS: Investigator driven, prospective, multicenter, randomized study of patients with stable angina, coronary stenosis ≥50% determined by clinically indicated first-line CTA, and FFRCT ≤ 0.80 in whom coronary revascularization was deferred. Patients are randomized to standard (atorvastatin 40 mg daily) or intensive (rosuvastatin 40 mg + ezetimibe 10 mg daily) lipid lowering therapy for 18 months. Coronary CTA scans with blinded coronary plaque and FFRCT analyses will be repeated after 9 and 18 months. The primary endpoint is the 18-month difference in FFRCT using (1) the FFRCT value 2 cm distal to stenosis and (2) the lowest distal value in the vessel of interest. A total of 104 patients will be included in the study. CONCLUSION: The results of this study will provide novel insights into the interplay between lipid lowering, and the pathophysiology in coronary artery disease.

Temporal changes and clinical significance of peridevice leak following left atrial appendage occlusion with Amplatzer devices.

BACKGROUND: The natural history of peridevice leak (PDL) following left atrial appendage occlusion (LAAO) is unknown. This study sought to investigate changes of PDL from 2 until 12 months after LAAO, using cardiac computed tomography (CT), and to assess the potential association between persistent PDL and clinical outcomes METHODS: Single-center observational study of Amplatzer LAAO implants between 2010 and 2017 (n = 206). Patients with 2 and 12 months cardiac CT were included in the study (n = 153). Images were blindly analyzed. PDL was characterized by frequency and size at the device disc, lobe, and left atrial appendage contrast patency. Patients were followed for the composite outcome of ischemic stroke, transient ischemic attack, systemic embolism, or all-cause death. Median follow up from LAAO was 3.1 (2.3-4.3) years. RESULTS: Contrast patency was present in 101 (66%) and 72 (47%) (p < 0.001) at 2 and 12 months, respectively. PDL was identified at the disc in 103 (67%) patients at 2 months versus 93 (61%) at 12 months (p = 0.08), and at the lobe in 29 (19%) at both time points. PDL area at the disc did not change significantly over time, ∆$\unicode{x02206}$ area: -8.95 mm (95% confidence interval [CI]: -18.9; 1.01) p = 0.08. Permanent atrial fibrillation was independently associated with persistent PDL. Persistent versus no PDL was associated with a 62% worse clinical outcome, however not statistically significant, hazard ratio (HR): 1.62 (95% CI: 0.9-2.93), p = 0.11. CONCLUSION: Persistent PDL was frequently observed following LAAO with Amplatzer devices. The PDL frequency and size appeared unchanged between 2 and 12 months. Persistent PDL was not significantly associated with worse clinical outcomes, yet this needs further delineation in future studies.

Coronary volume to left ventricular mass ratio in patients with diabetes mellitus.

BACKGROUND: Diabetes mellitus is a major risk factor for coronary artery disease (CAD) and may provoke structural and functional changes in coronary vasculature. The coronary volume to left ventricular mass (V/M) ratio is a new anatomical parameter capable of revealing a potential physiological imbalance between coronary vasculature and myocardial mass. The aim of this study was to examine the V/M derived from coronary computed tomography angiography (CCTA) in patients with diabetes. METHODS: Patients with clinically suspected CAD enrolled in the ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry and known diabetic status were included. Coronary artery volume and left ventricular myocardial mass were analyzed from CCTA and the V/M ratio was calculated and compared between patients with and without diabetes. RESULTS: Of the 3053 patients (age 66 â€‹± â€‹10 years; 66% male) with known diabetic status, diabetes was present in 21.9%. Coronary volume was lower in patients with diabetes compared to those without diabetes (2850 â€‹± â€‹940 â€‹mm3 vs. 3040 â€‹± â€‹970 â€‹mm3, p â€‹< â€‹0.0001), whereas the myocardial mass was comparable between the 2 groups (122 â€‹± â€‹33 â€‹g vs. 122 â€‹± â€‹32 â€‹g, p â€‹= â€‹0.70). The V/M ratio was significantly lower in patients with diabetes (23.9 â€‹± â€‹6.8 â€‹mm3/g vs. 25.7 â€‹± â€‹7.5 â€‹mm3/g, p â€‹< â€‹0.0001). Among subjects with obstructive CAD (n â€‹= â€‹2191, 24.0% diabetics) and non-obstructive CAD (16.7% diabetics), the V/M ratio was significantly lower in patients with diabetes compared to those without (23.4 â€‹± â€‹6.7 â€‹mm3/g vs. 25.0 â€‹± â€‹7.3 â€‹mm3/g, p â€‹< â€‹0.0001 and 25.6 â€‹± â€‹6.9 â€‹mm3/g vs. 27.3 â€‹± â€‹7.6 â€‹mm3/g, respectively, p â€‹= â€‹0.006). CONCLUSION: The V/M ratio was significantly lower in patients with diabetes compared to non-diabetics, even after correcting for obstructive coronary stenosis. The clinical value of the reduced V/M ratio in diabetic patients needs further investigation.

Trans-lesional fractional flow reserve gradient as derived from coronary CT improves patient management: ADVANCE registry.

BACKGROUND: The role of change in fractional flow reserve derived from CT (FFRCT) across coronary stenoses (ΔFFRCT) in guiding downstream testing in patients with stable coronary artery disease (CAD) is unknown. OBJECTIVES: To investigate the incremental value of ΔFFRCT in predicting early revascularization and improving efficiency of catheter laboratory utilization. MATERIALS: Patients with CAD on coronary CT angiography (CCTA) were enrolled in an international multicenter registry. Stenosis severity was assessed as per CAD-Reporting and Data System (CAD-RADS), and lesion-specific FFRCT was measured 2 â€‹cm distal to stenosis. ΔFFRCT was manually measured as the difference of FFRCT across visible stenosis. RESULTS: Of 4730 patients (66 â€‹± â€‹10 years; 34% female), 42.7% underwent ICA and 24.7% underwent early revascularization. ΔFFRCT remained an independent predictor for early revascularization (odds ratio per 0.05 increase [95% confidence interval], 1.31 [1.26-1.35]; p â€‹< â€‹0.001) after adjusting for risk factors, stenosis features, and lesion-specific FFRCT. Among the 3 models (model 1: risk factors â€‹+ â€‹stenosis type and location â€‹+ â€‹CAD-RADS; model 2: model 1 â€‹+ â€‹FFRCT; model 3: model 2 â€‹+ â€‹ΔFFRCT), model 3 improved discrimination compared to model 2 (area under the curve, 0.87 [0.86-0.88] vs 0.85 [0.84-0.86]; p â€‹< â€‹0.001), with the greatest incremental value for FFRCT 0.71-0.80. ΔFFRCT of 0.13 was the optimal cut-off as determined by the Youden index. In patients with CAD-RADS ≥3 and lesion-specific FFRCT ≤0.8, a diagnostic strategy incorporating ΔFFRCT >0.13, would potentially reduce ICA by 32.2% (1638-1110, p â€‹< â€‹0.001) and improve the revascularization to ICA ratio from 65.2% to 73.1%. CONCLUSIONS: ΔFFRCT improves the discrimination of patients who underwent early revascularization compared to a standard diagnostic strategy of CCTA with FFRCT, particularly for those with FFRCT 0.71-0.80. ΔFFRCT has the potential to aid decision-making for ICA referral and improve efficiency of catheter laboratory utilization.

Prognostic value of coronary computed tomography angiographic derived fractional flow reserve: a systematic review and meta-analysis.

OBJECTIVES: To obtain more powerful assessment of the prognostic value of fractional flow reserveCT testing we performed a systematic literature review and collaborative meta-analysis of studies that assessed clinical outcomes of CT-derived calculation of FFR (FFRCT) (HeartFlow) analysis in patients with stable coronary artery disease (CAD). METHODS: We searched PubMed and Web of Science electronic databases for published studies that evaluated clinical outcomes following fractional flow reserveCT testing between 1 January 2010 and 31 December 2020. The primary endpoint was defined as 'all-cause mortality (ACM) or myocardial infarction (MI)' at 12-month follow-up. Exploratory analyses were performed using major adverse cardiovascular events (MACEs, ACM+MI+unplanned revascularisation), ACM, MI, spontaneous MI or unplanned (>3 months) revascularisation as the endpoint. RESULTS: Five studies were identified including a total of 5460 patients eligible for meta-analyses. The primary endpoint occurred in 60 (1.1%) patients, 0.6% (13/2126) with FFRCT>0.80% and 1.4% (47/3334) with FFRCT ≤0.80 (relative risk (RR) 2.31 (95% CI 1.29 to 4.13), p=0.005). Likewise, MACE, MI, spontaneous MI or unplanned revascularisation occurred more frequently in patients with FFRCT ≤0.80 versus patients with FFRCT >0.80. Each 0.10-unit FFRCT reduction was associated with a greater risk of the primary endpoint (RR 1.67 (95% CI 1.47 to 1.87), p<0.001). CONCLUSIONS: The 12-month outcomes in patients with stable CAD show low rates of events in those with a negative FFRCT result, and lower risk of an unfavourable outcome in patients with a negative test result compared with patients with a positive test result. Moreover, the FFRCT numerical value was inversely associated with outcomes.

Cardiac computed tomography-derived coronary artery volume to myocardial mass.

In the absence of disease impacting the coronary arteries or myocardium, there exists a linear relationship between vessel volume and myocardial mass to ensure balanced distribution of blood supply. This balance may be disturbed in diseases of either the coronary artery tree, the myocardium, or both. However, in contemporary evaluation the coronary artery anatomy and myocardium are assessed separately. Recently the coronary lumen volume to myocardial mass ratio (V/M), measured noninvasively using coronary computed tomography angiography (CTCA), has emerged as an integrated measure of myocardial blood supply and demand in vivo. This has the potential to yield new insights into diseases where this balance is altered, thus impacting clinical diagnoses and management. In this review, we outline the scientific methodology underpinning CTCA-derived measurement of V/M. We describe recent studies describing alterations in V/M across a range of cardiovascular conditions, including coronary artery disease, cardiomyopathies and coronary microvascular dysfunction. Lastly, we highlight areas of unmet research need and future directions, where V/M may further enhance our understanding of the pathophysiology of cardiovascular disease.

Coronary CT angiography derived FFR in patients with left main disease.

The presence of left main coronary artery disease (LMCAD) is associated with an unfavorable clinical outcome. The clinical utility of FFRCT testing for non-invasive physiological assessment in LMCAD remains largely unknown. In this single center observational study LMCAD patients were retrospectively identified between November 2015 and December 2017. We evaluated the relationship between LMCAD diameter stenosis and downstream FFRCT values, and the clinical consequences following FFRCT testing in patients with LMCAD. The composite endpoint (all-cause death, myocardial infarction, unplanned revascularization) was determined over a median follow-up of 1.1 years. LMCAD was registered in 432 of 3202 (13%) patients having coronary CTA. FFRCT was prescribed in 213 (49%), while 59 (14%) patients were referred directly to invasive angiography or myocardial perfusion imaging. FFRCT was performed in 195 (45%) patients. LM stenosis severity was inversely related to downstream FFRCT values. In patients with simple LMCAD with stenosis ≥ 50%, > 80% had FFRCT > 0.80 in non-diseased proximal and downstream segments (n = 7). No patients with simple LMCAD and FFRCT > 0.80 (n = 20) suffered an adverse clinical outcome. FFRCT testing in patients with LMCAD is feasible. LM stenosis severity is inversely related to FFRCT value. Patients with LMCAD and FFRCT > 0.80 have favorable clinical outcomes at short-term follow-up. Large-scale studies assessing the clinical utility and safety of deferring invasive catheterization following FFRCT testing in patients with LMCAD are warranted.

Reduction of Myocardial Infarction and All-Cause Mortality Associated to Statins in Patients Without Obstructive CAD.

OBJECTIVES: The aim of this work was to evaluate the prognostic impact of statin therapy in symptomatic patients without obstructive CAD. BACKGROUND: Information on the prognostic impact of post-coronary computed tomographic angiography (CTA) statin use in patients with no or nonobstructive coronary artery disease (CAD) is sparse. METHODS: Patients undergoing CTA with suspected CAD in western Denmark from 2008 to 2017 with <50% coronary stenoses were identified. Information on post-CTA use of statin therapy and cardiovascular events were obtained from national registries. RESULTS: The study included 33,552 patients, median aged 56 years, 58% female, with no (n = 19,669) or nonobstructive (n = 13,883) CAD and a median follow-up of 3.5 years. The absolute risk of the combined end point of myocardial infarction (MI) or all-cause mortality was directly associated with the CAD burden with an event rate/1,000 patient-years of 4.13 (95% CI: 3.69-4.61) in no, 7.74 (95% CI: 6.88-8.71) in mild (coronary artery calcium score [CACS] 0-99), 13.72 (95% CI: 11.61-16.23) in moderate (CACS 100-399), and 32.47 (95% CI: 26.25-40.16) in severe (CACS ≥400) nonobstructive CAD. Statin therapy was associated with a multivariable adjusted HR for MI and death of 0.52 (95% CI: 0.36-0.75) in no, 0.44 (95% CI: 0.32-0.62) in mild, 0.51 (95% CI: 0.34-0.75) in moderate, and 0.52 (95% CI: 0.32-0.86) in severe nonobstructive CAD. The estimated numbers needed to treat to prevent the primary end point were 92 (95% CI: 61-182) in no, 36 (95% CI: 26-58) in mild, 24 (95% CI: 15-61) in moderate, and 13 (95% CI: 7-86) in severe nonobstructive CAD. Residual confounding may persist, but not to an extent explaining all of the observed risk reduction associated with statin treatment. CONCLUSIONS: The risk of MI and all-cause mortality in patients without obstructive CAD is directly associated with the CAD burden. Statin therapy is associated with a reduction of MI and all-cause death across the spectrum of CAD, however, the absolute benefit of treatment is directionally proportional with the CAD burden.

Rationale and design of the precise percutaneous coronary intervention plan (P3) study: Prospective evaluation of a virtual computed tomography-based percutaneous intervention planner.

INTRODUCTION: Fractional flow reserve (FFR) measured after percutaneous coronary intervention (PCI) has been identified as a surrogate marker for vessel related adverse events. FFR can be derived from standard coronary computed tomography angiography (CTA). Moreover, the FFR derived from coronary CTA (FFRCT ) Planner is a tool that simulates PCI providing modeled FFRCT values after stenosis opening. AIM: To validate the accuracy of the FFRCT Planner in predicting FFR after PCI with invasive FFR as a reference standard. METHODS: Prospective, international and multicenter study of patients with chronic coronary syndromes undergoing PCI. Patients will undergo coronary CTA with FFRCT prior to PCI. Combined morphological and functional evaluations with motorized FFR hyperemic pullbacks, and optical coherence tomography (OCT) will be performed before and after PCI. The FFRCT Planner will be applied by an independent core laboratory blinded to invasive data, replicating the invasive procedure. The primary objective is to assess the agreement between the predicted FFRCT post-PCI derived from the Planner and invasive FFR. A total of 127 patients will be included in the study. RESULTS: Patient enrollment started in February 2019. Until December 2020, 100 patients have been included. Mean age was 64.1 ± 9.03, 76% were males and 24% diabetics. The target vessels for PCI were LAD 83%, LCX 6%, and RCA 11%. The final results are expected in 2021. CONCLUSION: This study will determine the accuracy and precision of the FFRCT Planner to predict post-PCI FFR in patients with chronic coronary syndromes undergoing percutaneous revascularization.

Local Pressure Drives Low-Density Lipoprotein Accumulation and Coronary Atherosclerosis in Hypertensive Minipigs.

BACKGROUND: The mechanisms by which hypertension accelerates coronary artery disease are poorly understood. Patients with hypertension often have confounding humoral changes, and to date, no experimental models have allowed analysis of the isolated effect of pressure on atherosclerosis in a setting that recapitulates the dimensions and biomechanics of human coronary arteries. OBJECTIVES: This study sought to analyze the effect of pressure on coronary atherosclerosis and explore the underlying mechanisms. METHODS: Using inflatable suprarenal aortic cuffs, we increased mean arterial pressure by >30 mm Hg in the cephalad body part of wild-type and hypercholesterolemic proprotein convertase subtilisin kexin type 9 (PCSK9)D374Y Yucatan minipigs for >1 year. Caudal pressures remained normal. RESULTS: Under hypercholesterolemic conditions in PCSK9D374Y transgenic minipigs, cephalad hypertension accelerated coronary atherosclerosis to almost 5-fold with consistent development of fibroatheromas that were sufficiently large to cause stenosis on computed tomography angiography. This was caused by local pressure forces, because vascular beds shielded from hypertension, but exposed to the same humoral factors, showed no changes in lesion formation. The same experiment was conducted under normocholesterolemic conditions in wild-type minipigs to examine the underlying mechanisms. Hypertension produced clear changes in the arterial proteome with increased abundance of mechanical strength proteins and reduced levels of infiltrating plasma macromolecules. This was paralleled by increased smooth muscle cells and increased intimal accumulation of low-density lipoproteins in the coronary arteries. CONCLUSIONS: Increased pressure per se facilitates coronary atherosclerosis. Our data indicate that restructuring of the artery to match increased tensile forces in hypertension alters the passage of macromolecules and leads to increased intimal accumulation of low-density lipoproteins.

Temporal changes in FFRCT-Guided Management of Coronary Artery Disease - Lessons from the ADVANCE Registry.

BACKGROUND: The ADVANCE registry is a large prospective study of outcomes and resource utilization in patients undergoing coronary computed tomography angiography (CCTA) and CT-based fractional flow reserve (FFRCT). As experience with new technologies and practices develops over time, we investigated temporal changes in the use of FFRCT within the ADVANCE registry. METHODS: 5083 patients with coronary artery disease (CAD) on CCTA were prospectively enrolled in the ADVANCE registry and were divided into 3 equally sized cohorts based on the temporal order of enrollment per site. Demographics, CCTA and FFRCT findings, and clinical outcomes through 1-year follow-up, were recorded and compared between tertiles. RESULTS: The number of patients with a ≥70% stenosis on CCTA was similar over time (33.6%, 30.9%, and 33.8% for cohort 1-3). The rate of positive FFRCT ≤0.80 was higher for cohorts 2 (67.3%) and 3 (74.6%) than for cohort 1 (57.1%, p < 0.001). Invasive FFR rates decreased from 25.8% to 22.4% between cohort 1 and 3 (p = 0.023). Moreover, patients with a FFRCT ≤0.80 were less frequently referred for invasive coronary angiography (ICA) (from 62.9% to 52.9%, p < 0.001), and underwent fewer revascularizations between cohort 1 and 3 (from 41.9% to 32.0%, p < 0.001). The prevalence of major events was low (1.2%) and similar between cohorts. CONCLUSIONS: Growing experience with FFRCT improved the likelihood of identifying hemodynamically significant CAD and safely reduced the need for ICA and revascularization in patients with anatomically significant disease even in the instance of an abnormal FFRCT.

The clinical utility of FFRCT stratified by age.

BACKGROUND: CT coronary angiography (CTA) with Fractional Flow Reserve as determined by CT (FFRCT) is a safe alternative to invasive coronary angiography. A negative FFRCT has been shown to have low cardiac event rates compared to those with a positive FFRCT. However, the clinical utility of FFRCT according to age is not known. METHODS: Patients' in the ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry, were stratified into those ≥65 or <65 years of age. The impact of FFRCT on clinical decision-making, as assessed by patient age, was determined by evaluating patient management using CTA results alone, followed by site investigators submitting a report on the treatment plan based upon the newly provided FFRCT data. Outcomes at 1-year post CTA were assessed, including major adverse cardiovascular events (myocardial infarction, all-cause mortality or unplanned hospitalization for ACS leading to revascularisation) and total revascularisation. Positive FFRCT was deemed to be â€‹≤ â€‹0.8. RESULTS: FFRCT was calculated in 1849 (40.6%) subjects aged <65 and 2704 (59.4%) â€‹≥ â€‹65 years of age. Subjects ≥65 years were more likely to have anatomic obstructive disease on CTA (≥50% stenosis), compared to those aged <65 (69.7% and 73.2% respectively, p â€‹= â€‹0.008). There was a similar graded increase in recommended and actual revascularisation with either CABG or PCI, with declining FFRCT strata for subjects above and below the age of 65. MACE and revascularisation rates were not significantly different for those â€‹≥ â€‹or <65, regardless of FFRCT positivity or stenosis severity <50% or ≥50%. With a negative FFRCT result, and anatomical stenosis ≥50%, those â€‹≥ â€‹and <65 years of age, had similar rates of MACE (0.2% for both, p â€‹= â€‹0.1) and revascularisation (8.7% and 10.4% respectively p â€‹= â€‹0.4). Logistic regression analysis, with age as a continuous variable, and adjustment for Diamond Forrester Risk, baseline FFRCT and treatment (CABG, PCI, medical therapy), indicated a statistically significant, but small increase in the odds of a MACE event with increasing age (OR 1.04, 95% CI 1.006-1.08, p â€‹= â€‹0.02). Amongst patients with a FFRCT > 0.80, there was no effect of age on the odds of revascularisation. CONCLUSION: The findings of this study point to a low risk of MACE events or need for revascularisation in those aged â€‹≥ â€‹or <65 with a FFRCT>0.80, despite the higher incidence of anatomic obstructive CAD in those ≥65 years. The findings show the clinical usefulness and outcomes of FFRCT are largely constant regardless of age.

Coronary plaque burden in Turner syndrome a coronary computed tomography angiography study.

Turner syndrome (TS) is associated with coronary artery disease (CAD), an important cause of premature death in TS. However, the determinants of CAD in women with TS remain unknown. In a cross-sectional study design, 168 women without clinical evidence of CAD (115 with TS and 53 without TS) were assessed for the presence and volume of subclinical CAD using coronary CT angiography. Karyotype, the presence of congenital heart defects and conventional cardiovascular risk factors were also registered. Comparative analyses were performed (1) between women with and without TS and (2) in the TS group, between women with and without subclinical CAD. The prevalence of CAD, in crude and adjusted analyses, was not increased for women with TS (crude prevalence: 40 [35%] in TS vs. 25 [47%] in controls, p = 0.12). The volume of atherosclerosis was not higher in women with TS compared with controls (median and interquartile range 0 [0-92] in TS vs. 0 [0-81]mm3 in controls, p = 0.29). Among women with TS, women with subclinical CAD were older (46 ± 13 vs. 37 ± 11 years, p < 0.001), had higher blood pressure (systolic blood pressure 129 ± 16 vs. 121 ± 16 mmHg, p < 0.05) and were more frequently diagnosed with type 2 diabetes (5 [13%] vs. 2 [3%], p < 0.05). Karyotype or congenital heart defects were not associated with subclinical CAD. Some women with TS show early signs of CAD, however overall, not more than women without TS. Conventional cardiovascular risk factors were the principal determinants of CAD also in TS, and CAD prevention strategies should be observed.ClinicalTrial.gov Identifier: NCT01678261 ( https://clinicaltrials.gov/ct2/show/NCT01678261 ).

Clinical outcomes following real-world computed tomography angiography-derived fractional flow reserve testing in chronic coronary syndrome patients with calcification.

AIMS: This study sought to investigate outcomes following a normal CT-derived fractional flow reserve (FFRCT) result in patients with moderate stenosis and coronary artery calcification, and to describe the relationship between the extent of calcification, stenosis, and FFRCT. METHODS AND RESULTS: Data from 975 consecutive patients suspected of chronic coronary syndrome with stenosis (30-70%) determined by computed CT angiography and FFRCT to guide downstream management decisions were reviewed. Median (range) follow-up time was 2.2 (0.5-4.2) years. Coronary artery calcium (CAC) scores were ≥400 in 25%, stenosis ≥50% in 83%, and FFRCT >0.80 in 51% of the patients. There was a lower incidence of the composite endpoint (death, myocardial infarction, hospitalization for unstable angina, and unplanned coronary revascularization) at 4.2 years in patients with any CAC and FFRCT > 0.80 vs. FFRCT ≤ 0.80 (3.9% and 8.7%, P = 0.04), however, in patients with CAC scores ≥400 the risk difference between groups did not reach statistical significance, 4.2% vs. 9.7% (P = 0.24). A negative relationship between CAC scores and FFRCT irrespective of stenosis severity was demonstrated. CONCLUSION: FFRCT shows promise in identifying patients with stenosis and calcification who can be managed without further downstream testing. Moreover, an inverse relationship between CAC levels and FFRCT was demonstrated. Studies are needed to further assess the clinical utility of FFRCT in patients with extensive coronary calcification.

1-Year Impact on Medical Practice and Clinical Outcomes of FFRCT: The ADVANCE Registry.

OBJECTIVES: The 1-year data from the international ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) Registry of patients undergoing coronary computed tomography angiography (CTA) was used to evaluate the relationship of fractional flow reserve derived from coronary CTA (FFRCT) with downstream care and clinical outcomes. BACKGROUND: Guidelines for management of chest pain using noninvasive imaging pathways are based on short- to intermediate-term outcomes. METHODS: Patients (N = 5,083) evaluated for clinically suspected coronary artery disease and in whom atherosclerosis was identified by coronary CTA were prospectively enrolled at 38 international sites from July 15, 2015, to October 20, 2017. Demographics, symptom status, coronary CTA and FFRCT findings and resultant site-based treatment plans, and clinical outcomes through 1 year were recorded and adjudicated by a blinded core laboratory. Major adverse cardiac events (MACE), death, myocardial infarction (MI), and acute coronary syndrome leading to urgent revascularization were captured. RESULTS: At 1 year, 449 patients did not have follow-up data. Revascularization occurred in 1,208 (38.40%) patients with an FFRCT ≤0.80 and in 89 (5.60%) with an FFRCT >0.80 (relative risk [RR]: 6.87; 95% confidence interval [CI]: 5.59 to 8.45; p < 0.001). MACE occurred in 55 patients, 43 events occurred in patients with an FFRCT ≤0.80 and 12 occurred in those with an FFRCT >0.80 (RR: 1.81; 95% CI: 0.96 to 3.43; p = 0.06). Time to first event (all-cause death or MI) occurred in 38 (1.20%) patients with an FFRCT ≤0.80 compared with 10 (0.60%) patients with an FFRCT >0.80 (RR: 1.92; 95% CI: 0.96 to 3.85; p = 0.06). Time to first event (cardiovascular death or MI) occurred cardiovascular death or MI occurred more in patients with an FFRCT ≤0.80 compared with patients with an FFRCT >0.80 (25 [0.80%] vs. 3 [0.20%]; RR: 4.22; 95% CI: 1.28 to 13.95; p = 0.01). CONCLUSIONS: The 1-year outcomes from the ADVANCE FFRCT Registry show low rates of events in all patients, with less revascularization and a trend toward lower MACE and significantly lower cardiovascular death or MI in patients with a negative FFRCT compared with patients with abnormal FFRCT values. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Wave [ADVANCE]; NCT02499679).