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Left atrial (LA) sphericity has been proposed as a more sensitive marker of atrial fibrillation (AF)-associated atrial remodeling compared to traditional markers such as LA size. However, mechanisms that underlie changes in LA sphericity are not fully understood and studies investigating the predictive value of LA sphericity for AF ablation outcome have yielded conflicting results. The present study aimed to assess correlates of LA sphericity and to compare LA sphericity in subjects with and without AF. Measures of LA size (LA diameter, LA volume, LA volume index), LA sphericity and thoracic anteroposterior diameter (APd) at the level of the LA were determined using computed tomography (CT) imaging data in 293 AF patients (62% paroxysmal AF) and 110 controls. LA diameter (40.1 ± 6.8 mm vs. 35.2 ± 5.1 mm; p < 0.001), LA volume (116.0 ± 33.0 ml vs. 80.3 ± 22.6 ml; p < 0.001) and LA volume index (56.1 ± 15.3 ml/m2 vs. 41.6 ± 11.1 ml/m2; p < 0.001) were significantly larger in AF patients compared to controls, also after adjustment for covariates. LA sphericity did not differ between AF patients and controls (83.7 ± 2.9 vs. 83.9 ± 2.4; p = 0.642). Multivariable linear regression analysis demonstrated that LA diameter, LA volume, female sex, body length and thoracic APd were independently associated with LA sphericity. The present study suggests that thoracic constraints rather than the presence of AF determine LA sphericity, implying LA sphericity to be unsuitable as a marker of AF-related atrial remodeling. • The present study is first to assess left atrial sphericity in a significant number of control subjects. • LA sphericity did not differ between AF patients and controls. • Thoracic constraints rather than the presence of AF determine LA sphericity. • This study suggests that LA sphericity is unsuitable as a marker of AF-related atrial remodeling. [ABSTRACT FROM AUTHOR]

Background: Atherosclerotic plaque characteristics may affect downstream myocardial perfusion, as well as coronary lesion severity.Objectives: This study sought to evaluate the association between quantitative plaque burden and plaque morphology obtained using coronary computed tomography angiography (CTA) and quantitative myocardial perfusion obtained using [15O]H2O positron emission tomography (PET), as well as fractional flow reserve (FFR) derived invasively.Methods: Two hundred eight patients (63% men; age 58 ± 8.7 years) with suspected coronary artery disease were prospectively included. All patients underwent 256-slice coronary CTA, [15O]H2O PET, and invasive FFR measurements. Coronary CTA-derived plaque burden and morphology were assessed using commercially available software and compared with PET perfusion and FFR.Results: Atherosclerotic plaques were present in 179 patients (86%) and 415 of 610 (68%) evaluable coronary arteries. On a per-vessel basis, traditional coronary plaque burden indexes, such as plaque length and volume, minimal lumen area, and stenosis percentage, were significantly associated with impaired hyperemic myocardial blood flow (MBF) and FFR. In addition, morphological features, such as partially calcified plaques, positive remodeling (PR), and low attenuation plaque, displayed a negative impact on hyperemic MBF and FFR. Multivariable analysis revealed that the morphological feature of PR was independently related to impaired hyperemic MBF as well as an unfavorable FFR (p = 0.004 and p = 0.007, respectively), next to stenosis percentage (p = 0.001 and p < 0.001, respectively) and noncalcified plaque volume (p < 0.001 and p = 0.010, respectively).Conclusions: PR and noncalcified plaque volume are associated with detrimental downstream hyperemic myocardial perfusion and FFR, independent of lesion severity. [ABSTRACT FROM AUTHOR]

Purpose To determine lifetime cost-effectiveness of diagnostic evaluation strategies for individuals with stable chest pain and suspected coronary artery disease (CAD). Methods Exercise treadmill testing (ETT), stress echocardiography (SE), myocardial perfusion scintigraphy (MPS), coronary computed tomographic angiography (CCTA), and invasive coronary angiography (ICA) were assessed alone, or in succession to each other. Results Initial ETT followed by imaging wherein ETT was equivocal or unable to be performed appeared more cost-effective than any strategy employing initial testing by imaging. Conclusion As pre-test likelihood of CAD varies, different modalities including SE, CCTA, and MPS result in improved costs and enhanced effectiveness. [ABSTRACT FROM AUTHOR]

Background: Fractional flow reserve (FFR) has emerged as the invasive gold standard for assessing vessel-specific ischemia. However, FFR measurements are influenced by the hydrostatic effect, which might adversely impact the assessment of ischemia., Aims: This study aimed to investigate the impact of hydrostatic pressure on FFR measurements by correcting for the height and comparing FFR with [ 15 O]H 2 O positron emission tomography (PET)-derived relative flow reserve (RFR)., Methods: The 206 patients were included in this analysis. Patients underwent coronary computed tomography angiography (CCTA), [ 15 O]H 2 O PET, and invasive coronary angiography with routine FFR in every epicardial artery. Height differences between the aortic guiding catheter and distal pressure sensor were quantified on CCTA images. An FFR ≤ 0.80 was considered significant., Results: The study found a reclassification in 7% of the coronary arteries. Notably, 11% of left anterior descending (LAD) arteries were reclassified from hemodynamically significant to nonsignificant. Conversely, 6% of left circumflex (Cx) arteries were reclassified from nonsignificant to significant. After correcting for the hydrostatic pressure effect, the correlation between FFR and PET-derived RFR increased significantly from r = 0.720 to r = 0.786 (p = 0.009). The average magnitude of correction was +0.05 FFR units in the LAD, -0.03 in the Cx, and -0.02 in the right coronary artery., Conclusion: Hydrostatic pressure has a small but clinically relevant influence on FFR measurements obtained with a pressure wire. Correcting for this hydrostatic error significantly enhances the correlation between FFR and PET-derived RFR., (© 2024 Wiley Periodicals LLC.)

Importance: Lipoprotein(a) (Lp[a]) is a causal risk factor for cardiovascular disease; however, long-term effects on coronary atherosclerotic plaque phenotype, high-risk plaque formation, and pericoronary adipose tissue inflammation remain unknown., Objective: To investigate the association of Lp(a) levels with long-term coronary artery plaque progression, high-risk plaque, and pericoronary adipose tissue inflammation., Design, Setting, and Participants: This single-center prospective cohort study included 299 patients with suspected coronary artery disease (CAD) who underwent per-protocol repeated coronary computed tomography angiography (CCTA) imaging with an interscan interval of 10 years. Thirty-two patients were excluded because of coronary artery bypass grafting, resulting in a study population of 267 patients. Data for this study were collected from October 2008 to October 2022 and analyzed from March 2023 to March 2024., Exposures: The median scan interval was 10.2 years. Lp(a) was measured at follow-up using an isoform-insensitive assay. CCTA scans were analyzed with a previously validated artificial intelligence-based algorithm (atherosclerosis imaging-quantitative computed tomography)., Main Outcome and Measures: The association between Lp(a) and change in percent plaque volumes was investigated in linear mixed-effects models adjusted for clinical risk factors. Secondary outcomes were presence of low-density plaque and presence of increased pericoronary adipose tissue attenuation at baseline and follow-up CCTA imaging., Results: The 267 included patients had a mean age of 57.1 (SD, 7.3) years and 153 were male (57%). Patients with Lp(a) levels of 125 nmol/L or higher had twice as high percent atheroma volume (6.9% vs 3.0%; P = .01) compared with patients with Lp(a) levels less than 125 nmol/L. Adjusted for other risk factors, every doubling of Lp(a) resulted in an additional 0.32% (95% CI, 0.04-0.60) increment in percent atheroma volume during the 10 years of follow-up. Every doubling of Lp(a) resulted in an odds ratio of 1.23 (95% CI, 1.00-1.51) and 1.21 (95% CI, 1.01-1.45) for the presence of low-density plaque at baseline and follow-up, respectively. Patients with higher Lp(a) levels had increased pericoronary adipose tissue attenuation around both the right coronary artery and left anterior descending at baseline and follow-up., Conclusions and Relevance: In this long-term prospective serial CCTA imaging study, higher Lp(a) levels were associated with increased progression of coronary plaque burden and increased presence of low-density noncalcified plaque and pericoronary adipose tissue inflammation. These data suggest an impact of elevated Lp(a) levels on coronary atherogenesis of high-risk, inflammatory, rupture-prone plaques over the long term.

Background: The diagnostic performance of non-invasive imaging techniques for detecting obstructive coronary artery disease (CAD) in patients with a history of myocardial infarction or percutaneous coronary intervention has not been comprehensively evaluated. This meta-analysis assesses the diagnostic value of coronary CT angiography (CCTA), CCTA combined with CT perfusion (CCTA+CTP), cardiac MRI (CMR) and single-photon emission CT (SPECT) compared with invasive reference standards., Methods: We systematically searched PubMed, Embase, Web of Science and the Cochrane Library from 2005 to September 2022 for prospective, blinded studies including populations with ≥50% prior CAD., Results: We identified 18 studies encompassing 3265 patients, with obstructive CAD present in 64%. The per-patient sensitivity of CCTA (0.95; 95% CI 0.92 to 0.98), CCTA+CTP (0.93; 95% CI 0.84 to 0.98) and CMR (0.91; 95% CI 0.86 to 0.94) was high, while SPECT showed lower sensitivity (0.63; 95% CI 0.52 to 0.73). SPECT had higher specificity compared with CCTA (0.66; 95% CI 0.56 to 0.76 vs 0.37; 95% CI 0.29 to 0.46), but was comparable to CCTA+CTP (0.59; 95% CI 0.49 to 0.69) and CMR (0.69; 95% CI 0.53 to 0.81). The area under the curve for SPECT was the lowest (0.70; 95% CI 0.58 to 0.87), while CCTA (0.91; 95% CI 0.86 to 0.98), CCTA+CTP (0.89; 95% CI 0.73 to 1.00) and CMR (0.91; 95% CI 0.80 to 1.00) showed similar high values., Conclusions: In patients with prior CAD, CCTA, CCTA+CTP and CMR demonstrated high diagnostic performance, whereas SPECT had lower sensitivity. These findings can guide the selection of non-invasive imaging techniques in this high-risk population., Prospero Registration Number: CRD42022322348., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To investigate the location-specific prognostic significance of plaque burden, diameter stenosis and plaque morphology., Methods and Results: Patients without a documented cardiac history who underwent coronary computed tomography angiography (CCTA) for suspected coronary artery disease were included. Percentage atheroma volume (PAV), maximum diameter stenosis, and plaque morphology were assessed and classified into proximal, mid, or distal segments of the coronary tree. Major adverse cardiac events (MACE) were defined as death or non-fatal myocardial infarction. Among 2819 patients 267 events (9.5%) occurred during a median follow-up of 6.9 years. When adjusted for traditional risk factors and presence of PAV on other locations, only proximal PAV was independently associated with MACE. However, PAV of the proximal segments was strongly correlated to PAV localized at the mid (R= 0.76) and distal segments (R=0.74, p<0.01 for both). When only adjusted for cardiovascular risk factors, the area under the curve (AUC) to predict MACE for proximal PAV was 0.73 (95%CI 0.69-0.76), which was similar compared to mid PAV (AUC 0.72, 95%CI 0.68-0.76) and distal PAV (AUC 0.72, 95%CI 0.68-0.76). Similar results were obtained using diameter stenosis instead of PAV. The presence of proximal low-attenuation plaque had borderline additional prognostic value., Conclusions: Proximal PAV was the strongest predictor of MACE when adjusted for cardiovascular risk factors and plaque at other locations. However, when presence of plaque was only adjusted for cardiovascular risk factors, proximal, mid, and distal plaque localization showed a similar predictive ability for MACE., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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-QCT ISCHEMIA ) 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 (FFR CT ), and invasive coronary angiography in conjunction with invasive FFR measurements. The AI-QCT ISCHEMIA 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-QCT ISCHEMIA , 0.69 (95% CI: 0.63-0.74; P < 0.001) for FFR CT , 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-QCT ISCHEMIA , 0.78 (95% CI: 0.72-0.84; P = 0.037) for FFR CT , 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-QCT ISCHEMIA test was associated with aHR: 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., Competing Interests: Funding Support and Author Disclosures This project has been supported by the Foundation “De Drie Lichten” in the Netherlands. Dr Nurmohamed has received grants from the Dutch Heart Foundation (Dekker 03-007-2023-0068) and grants from the European Atherosclerosis Society (2023); and is co-founder of Lipid Tools. Mr Wang, Dr Chan, Ms Crabtree, Ms Aquino, Dr Min, and Dr Earls are employees of Cleerly Inc. Dr Choi has received grant support from GW Heart and Vascular Institute; equity in Cleerly, Inc; and has received consulting fees from Siemens Healthineers. Dr Knaapen has received research grants from HeartFlow, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Various non-invasive images are used in clinical practice for the diagnosis and prognostication of chronic coronary syndromes. Notably, quantitative myocardial perfusion imaging (MPI) through positron emission tomography (PET) has seen significant technical advancements and a substantial increase in its use over the past two decades. This progress has generated an unprecedented wealth of clinical information, which, when properly applied, can diagnose and fine-tune the management of patients with different types of ischemic syndromes. This state-of-art review focuses on quantitative PET MPI, its integration into clinical practice, and how it holds up at the eyes of modern cardiac imaging and revascularization clinical trials, along with future perspectives., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Currently, cutoffs of quantitative [ 15 O]H 2 O PET to detect fractional flow reserve (FFR)-defined coronary artery disease (CAD) were derived from a single cohort that included patients without prior CAD. However, prior CAD, sex, and age can influence myocardial blood flow (MBF). Therefore, the present study determined the influence of prior CAD, sex, and age on optimal cutoffs of hyperemic MBF (hMBF) and coronary flow reserve (CFR) and evaluated whether cutoff optimization enhanced diagnostic performance of quantitative [ 15 O]H 2 O PET against an FFR reference standard. Methods: Patients with chronic coronary symptoms underwent [ 15 O]H 2 O PET and invasive coronary angiography with FFR. Optimal cutoffs for patients with and without prior CAD and subpopulations based on sex and age were determined. Results: This multicenter study included 560 patients. Optimal cutoffs were similar for patients with ( n = 186) and without prior CAD (hMBF, 2.3 vs. 2.3 mL·min -1 ·g -1 ; CFR, 2.7 vs. 2.6). Females ( n = 190) had higher hMBF cutoffs than males (2.8 vs. 2.3 mL·min -1 ·g -1 ), whereas CFRs were comparable (2.6 vs. 2.7). However, female sex-specific hMBF cutoff implementation decreased diagnostic accuracy as compared with the cutoff of 2.3 mL·min -1 ·g -1 (72% vs. 82%, P < 0.001). Patients aged more than 70 y ( n = 79) had lower hMBF (1.7 mL·min -1 ·g -1 ) and CFR (2.3) cutoffs than did patients aged 50 y or less, 51-60 y, and 61-70 y (hMBF, 2.3-2.4 mL·min -1 ·g -1 ; CFR, 2.7). Age-specific cutoffs in patients aged more than 70 y yielded comparable accuracy to the previously established cutoffs (hMBF, 72% vs. 76%, P = 0.664; CFR, 80% vs. 75%, P = 0.289). Conclusion: Patients with and without prior CAD had similar [ 15 O]H 2 O PET cutoffs for detecting FFR-defined significant CAD. Stratifying patients according to sex and age led to different optimal cutoffs; however, these values did not translate into an increased overall accuracy as compared with previously established thresholds for MBF., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Clinical risk scores based on traditional risk factors of atherosclerosis correlate imprecisely to an individual's complex pathophysiological predisposition to atherosclerosis and provide limited accuracy for predicting major adverse cardiovascular events (MACE). Over the past two decades, computed tomography scanners and techniques for coronary computed tomography angiography (CCTA) analysis have substantially improved, enabling more precise atherosclerotic plaque quantification and characterization. The accuracy of CCTA for quantifying stenosis and atherosclerosis has been validated in numerous multicentre studies and has shown consistent incremental prognostic value for MACE over the clinical risk spectrum in different populations. Serial CCTA studies have advanced our understanding of vascular biology and atherosclerotic disease progression. The direct disease visualization of CCTA has the potential to be used synergistically with indirect markers of risk to significantly improve prevention of MACE, pending large-scale randomized evaluation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Same-day discharge (SDD) in patients undergoing percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) is appealing because of the increased patient comfort. However, data on SDD following large-bore vascular access are scarce., Aims: We investigated the feasibility and safety of SDD in patients undergoing large-bore CTO PCI., Methods: Between 2013 and 2023, 948 patients were prospectively enrolled in a single-centre CTO registry and underwent CTO PCI. SDD was pursued in all patients. Large-bore access was defined as the use of ≥7 French (Fr) sheaths in ≥1 access site. A logistic regression analysis was used to identify predictors for non-SDD. Clinical follow-up was obtained at 30 days., Results: SDD was observed in 62% of patients. Large-bore access was applied in 99% of the cohort. SDD patients were younger and more often male, with lower rates of renal insufficiency and prior coronary artery bypass grafting. Local access site bleeding (odds ratio [OR] 8.53, 95% confidence interval [CI]: 5.24-13.87) and vascular access complications (OR 7.23, 95% CI: 1.98-26.32) made hospitalisation more likely, with vascular access complications occurring in 3%. At 30 days, the hospital readmission rate was low in both SDD and non-SDD patients (5% vs 7%; p=non-significant). Finally, SDD was not a predictor for major adverse cardiovascular events (MACE) at follow-up., Conclusions: Same-day discharge can be achieved in the majority of patients undergoing CTO PCI with large-bore (≥7 Fr) access. Similar low hospital readmission and MACE rates between SDD and non-SDD patients at 30 days demonstrate the feasibility and safety of SDD.

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. The aim of this study was to validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [ 15 O]H 2 O positron emission tomography (PET) imaging. A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [ 15 O]H 2 O PET with quantitative assessment of resting and hyperemic myocardial perfusion. Within a 2 week period, coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. PET derived regional hyperemic myocardial blood flow (hMBF) and myocardial perfusion reserve (MPR) served as reference standards. In coronary arteries with stenoses (43%, 136 of 320), the overall diagnostic accuracies of RFR, dPR, and FFR did not differ when PET hyperemic MBF < 2.3 ml min -1 (69.9%, 70.6%, and 77.1%, respectively) and PET MPR < 2.5 (70.6%, 71.3%, and 66.9%, respectively) were considered as the reference for myocardial ischemia. Non-significant differences between the areas under the receiver operating characteristic (ROC) curve were found between the different indices. Furthermore, the integration of FFR with RFR (or dPR) does not enhance the diagnostic information already achieved by FFR in the characterization of ischemia via PET perfusion. In conclusion, the novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance comparable to FFR in assessing regional myocardial ischemia. These findings suggest that RFR and dPR may be considered as an FFR alternative for invasively guiding revascularization treatment in symptomatic patients with CAD., (© 2024. The Author(s).)

Background: The recent development of artificial intelligence-guided quantitative coronary computed tomography angiography analysis (AI-QCT) has enabled rapid analysis of atherosclerotic plaque burden and characteristics., Objectives: This study set out to investigate the 10-year prognostic value of atherosclerotic burden derived from AI-QCT and to compare the spectrum of plaque to manually assessed coronary computed tomography angiography (CCTA), coronary artery calcium scoring (CACS), and clinical risk characteristics., Methods: This was a long-term follow-up study of 536 patients referred for suspected coronary artery disease. CCTA scans were analyzed with AI-QCT and plaque burden was classified with a plaque staging system (stage 0: 0% percentage atheroma volume [PAV]; stage 1: >0%-5% PAV; stage 2: >5%-15% PAV; stage 3: >15% PAV). The primary major adverse cardiac event (MACE) outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, and all-cause mortality., Results: The mean age at baseline was 58.6 years and 297 patients (55%) were male. During a median follow-up of 10.3 years (IQR: 8.6-11.5 years), 114 patients (21%) experienced the primary outcome. Compared to stages 0 and 1, patients with stage 3 PAV and percentage of noncalcified plaque volume of >7.5% had a more than 3-fold (adjusted HR: 3.57; 95% CI 2.12-6.00; P < 0.001) and 4-fold (adjusted HR: 4.37; 95% CI: 2.51-7.62; P < 0.001) increased risk of MACE, respectively. Addition of AI-QCT improved a model with clinical risk factors and CACS at different time points during follow-up (10-year AUC: 0.82 [95% CI: 0.78-0.87] vs 0.73 [95% CI: 0.68-0.79]; P < 0.001; net reclassification improvement: 0.21 [95% CI: 0.09-0.38]). Furthermore, AI-QCT achieved an improved area under the curve compared to Coronary Artery Disease Reporting and Data System 2.0 (10-year AUC: 0.78; 95% CI: 0.73-0.83; P = 0.023) and manual QCT (10-year AUC: 0.78; 95% CI: 0.73-0.83; P = 0.040), although net reclassification improvement was modest (0.09 [95% CI: -0.02 to 0.29] and 0.04 [95% CI: -0.05 to 0.27], respectively)., Conclusions: Through 10-year follow-up, AI-QCT plaque staging showed important prognostic value for MACE and showed additional discriminatory value over clinical risk factors, CACS, and manual guideline-recommended CCTA assessment., Competing Interests: Funding Support and Author Disclosures Dr Nurmohamed is co-founder of Lipid Tools. Dr Stroes has received lecturing/advisory board fees from Amgen, Novartis, Esperion, Sanofi-Regeneron, and Akcea. Drs Min and Earls are employees of and hold equity in Cleerly Inc. Dr Choi has received grant support from GW Heart and Vascular Institute; holds equity in Cleerly, Inc; and has provided consulting services to Siemens Healthineers. Dr Knaapen has received research grants from HeartFlow, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In patients evaluated for obstructive coronary artery disease (CAD), guidelines recommend using either fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) to guide coronary revascularization decision-making. The hemodynamic significance of lesions with discordant FFR and iFR measurements is debated. This study compared [ 15 O]H 2 O PET-derived absolute myocardial perfusion between vessels with concordant and discordant FFR and iFR measurements. Methods: We included 197 patients suspected of obstructive CAD who had undergone [ 15 O]H 2 O PET perfusion imaging and combined FFR/iFR interrogation in 468 vessels. Resting myocardial blood flow (MBF), hyperemic MBF, and coronary flow reserve (CFR) were compared among 4 groups: FFR low/iFR low ( n = 79), FFR high/iFR low ( n = 22), FFR low/iFR high ( n = 22), and FFR high/iFR high ( n = 345). Predefined [ 15 O]H 2 O PET thresholds for ischemia were 2.3 mL·min -1 ·g -1 or less for hyperemic MBF and 2.5 or less for CFR. Results: Hyperemic MBF was lower in the concordant low (2.09 ± 0.67 mL·min -1 ·g -1 ), FFR high/iFR low (2.41 ± 0.80 mL·min -1 ·g -1 ), and FFR low/iFR high (2.40 ± 0.69 mL·min -1 ·g -1 ) groups compared with the concordant high group (2.91 ± 0.84 mL·min -1 ·g -1 ) ( P < 0.001, P = 0.004, and P < 0.001, respectively). A lower CFR was observed in the concordant low (2.37 ± 0.76) and FFR high/iFR low (2.64 ± 0.84) groups compared with the concordant high group (3.35 ± 1.07, P < 0.01 for both). However, for vessels with either low FFR or low iFR, quantitative hyperemic MBF and CFR values exceeded the ischemic threshold in 38% and 49%, respectively. In addition, resting MBF exhibited a negative correlation with iFR ( P < 0.001) and was associated with FFR low/iFR high discordance compared with concordant low FFR/low iFR measurements, independent of clinical and angiographic characteristics, as well as hyperemic MBF (odds ratio [OR], 0.41; 95% CI, 0.26-0.65; P < 0.001). Conclusion: We found reduced myocardial perfusion in vessels with concordant low and discordant FFR/iFR measurements. However, FFR/iFR combinations often inaccurately classified vessels as either ischemic or nonischemic when compared with hyperemic MBF and CFR. Furthermore, a lower resting MBF was associated with a higher iFR and the occurrence of FFR low/iFR high discordance. Our study showed that although combined FFR/iFR assessment can be useful to estimate the hemodynamic significance of coronary lesions, these pressure-derived indices provide a limited approximation of [ 15 O]H 2 O PET-derived quantitative myocardial perfusion as the physiologic standard of CAD severity., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Multivalvular heart disease (MVD) implies the presence of concomitant valvular lesions on two or more heart valves. This condition has become common in the few last years, mostly due to population aging. Every combination of valvular lesions uniquely redefines the hemodynamics of a patient. Over time, this may lead to alterations in left ventricle (LV) dimensions, shape and, eventually, function. Since most of the echocardiographic parameters routinely used in the valvular assessment have been developed in the context of single valve disease and are frequently flow- and load-dependent, their indiscriminate use in the context of MVD can potentially lead to errors in judging lesion severity. Moreover, the combination of non-severe lesions may still cause severe hemodynamic consequences, and thereby systolic dysfunction. This review aims to discuss the most frequent combinations of MVD and their echocardiographic caveats, while addressing the opportunities for a multimodality assessment to achieve a better understanding and treatment of these patients., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alexander R. van Rosendael is a member, Cleerly Scientific Advisory Board. Tami Crabtree is an employee and equity holder, Cleerly, Inc. Gianluca Pontone has received honorarium as speaker/consultant and/or institutional research grant from GE Healthcare, Bracco, Medtronic, Novartis. Ronny R. Buechel reports receiving speaking honoraria from GE Healthcare, Pfizer, Gilead, and IBA. Christoph Gräni received funding from the Swiss National Science foundation, InnoSuisse, CAIM foundation, GAMBIT foundation, Novartis foundation for biomedical research, outside of the submitted work. Andrew D. Choi is a consultant for Siemens, holds equity in Cleerly, and receives grant support from the George Washing Heart and Vascular Institute.Carlos E. Rochitte reports receiving speaking honoraria for Pfizer, Edwards, GE, and Manole. David M. German reports no conflicts Himanshu Gupta reports no conflicts. Omar Khalique is a consultant for Edwards, Croivalve, Restore Medical, holds equity in Triflo, and has received honoraria for educational programs from Heartflow. Udo Hoffmann is an employee and equity holder, Cleerly, Inc., and has received honoraria from Stanford University, Clinical Cardiovascular Sciences, Rapid AI, MedTrace. James Earls is an employee and equity holder, Cleerly, Inc. James K. Min is an employee and equity holder, Cleerly, Inc. and a member of the Arineta Medical Advisory Board. Ibrahim Danad is a member, Cleerly Scientific Advisory Board. Hugo Marques is a consultant for Cleerly, Inc., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: In chronic coronary syndrome (CCS) patients with documented coronary artery disease (CAD), ischaemia detection by myocardial perfusion imaging (MPI) and an invasive approach are viable diagnostic strategies. We compared the diagnostic performance of quantitative flow ratio (QFR) with single-photon emission computed tomography (SPECT), positron emission tomography (PET), and cardiac magnetic resonance imaging (CMR) in patients with prior CAD [previous percutaneous coronary intervention (PCI) and/or myocardial infarction (MI)]., Methods and Results: This PACIFIC-2 sub-study evaluated 189 CCS patients with prior CAD for inclusion. Patients underwent SPECT, PET, and CMR followed by invasive coronary angiography with fractional flow reserve (FFR) measurements of all major coronary arteries (N = 567), except for vessels with a sub-total or chronic total occlusion. Quantitative flow ratio computation was attempted in 488 (86%) vessels with measured FFR available (FFR ≤0.80 defined haemodynamically significant CAD). Quantitative flow ratio analysis was successful in 334 (68%) vessels among 166 patients and demonstrated a higher accuracy (84%) and sensitivity (72%) compared with SPECT (66%, P < 0.001 and 46%, P = 0.001), PET (65%, P < 0.001 and 58%, P = 0.032), and CMR (72%, P < 0.001 and 33%, P < 0.001). The specificity of QFR (87%) was similar to that of CMR (83%, P = 0.123) but higher than that of SPECT (71%, P < 0.001) and PET (67%, P < 0.001). Lastly, QFR exhibited a higher area under the receiver operating characteristic curve (0.89) than SPECT (0.57, P < 0.001), PET (0.66, P < 0.001), and CMR (0.60, P < 0.001)., Conclusion: QFR correlated better with FFR in patients with prior CAD than MPI, as reflected in the higher diagnostic performance measures for detecting FFR-defined, vessel-specific, significant CAD., Competing Interests: Conflict of interests: J.H.R., R.A.K., and J.T. are employees of Medis Medical Imaging. J.K. received consultancy fees from GE Healthcare and AstraZeneca and speaker fees from GE Healthcare, Bayer, Lundbeck, and Merck. P.K. received research grants from HeartFlow Inc. All others have no conflict of interests to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The Japanese Channel (J-Channel) score was introduced to aid in retrograde percutaneous coronary intervention (PCI) of chronic total coronary occlusions (CTOs). The predictive value of the J-Channel score has not been compared with established collateral grading systems such as the Rentrop classification and Werner grade., Aims: To investigate the predictive value of the J-Channel score, Rentrop classification and Werner grade for successful collateral channel (CC) guidewire crossing and technical CTO PCI success., Methods: A total of 600 prospectively recruited patients underwent CTO PCI. All grading systems were assessed under dual catheter injection. CC guidewire crossing was considered successful if the guidewire reached the distal segment of the CTO vessel through a retrograde approach. Technical CTO PCI success was defined as thrombolysis in myocardial infarction flow grade 3 and residual stenosis <30%., Results: Of 600 patients, 257 (43%) underwent CTO PCI through a retrograde approach. Successful CC guidewire crossing was achieved in 208 (81%) patients. The predictive value of the J-Channel score for CC guidewire crossing (area under curve 0.743) was comparable with the Rentrop classification (0.699, p = 0.094) and superior to the Werner grade (0.663, p = 0.002). Technical CTO PCI success was reported in 232 (90%) patients. The Rentrop classification exhibited a numerically higher discriminatory ability (0.676) compared to the J-Channel score (0.664) and Werner grade (0.589)., Conclusions: The J-channel score might aid in strategic collateral channel selection during retrograde CTO PCI. However, the J-Channel score, Rentrop classification, and Werner grade have limited value in predicting technical CTO PCI success., (© 2023 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Between 30-40% of patients with cardiac resynchronization therapy (CRT) do not show an improvement in left ventricular (LV) function. It is generally known that patient selection, LV lead implantation location, and device timing optimization are the three main factors that determine CRT response. Research has shown that image-guided CRT placement, which takes into account both anatomical and functional cardiac properties, positively affects the CRT response rate. In current clinical practice, a multimodality imaging approach comprised of echocardiography, cardiac magnetic resonance imaging, or nuclear medicine imaging is used to capture these features. However, with cardiac computed tomography (CT), one has an all-in-one acquisition method for both patient selection and the division of a patient-tailored, image-guided CRT placement strategy. This review discusses the applicability of CT in CRT patient identification, selection, and guided placement, offering insights into potential advancements in optimizing CRT outcomes.

Background: Coronary flow capacity (CFC) is a measure that integrates hyperemic myocardial blood flow and coronary flow reserve to quantify the pathophysiological impact of coronary artery disease on vasodilator capacity. This study explores the prognostic value of modified CFC derived from [ 15 O]H 2 O positron emission tomography perfusion imaging., Methods: Quantitative rest/stress perfusion measurements were obtained from 1300 patients with known or suspected coronary artery disease. Patients were classified as having myocardial steal (n=38), severely reduced CFC (n=141), moderately reduced CFC (n=394), minimally reduced CFC (n=245), or normal flow (n=482) using previously defined thresholds. The end point was a composite of death and nonfatal myocardial infarction., Results: During a median follow-up of 5.5 (interquartile range, 3.7-7.8) years, the end point occurred in 153 (12%) patients. Myocardial steal (hazard ratio [HR], 6.70 [95% CI, 3.21-13.99]; P <0.001), severely reduced CFC (HR, 2.35 [95% CI, 1.16-4.78]; P =0.018), and moderately reduced CFC (HR, 1.95 [95% CI, 1.11-3.41]; P =0.020) were associated with worse prognosis compared with normal flow, after adjusting for clinical characteristics. Similarly, in the overall population, increased resting myocardial blood flow (HR, 3.05 [95% CI, 1.68-5.54]; P <0.001), decreased hyperemic myocardial blood flow (HR, 0.68 [95% CI, 0.52-0.90]; P =0.007) and decreased coronary flow reserve (HR, 0.55 [95% CI, 0.42-0.71]; P <0.001) were independently associated with adverse outcome. In a model adjusted for the combined use of perfusion metrics, modified CFC demonstrated independent prognostic value (overall P =0.017)., Conclusions: [ 15 O]H 2 O positron emission tomography-derived resting myocardial blood flow, hyperemic myocardial blood flow, coronary flow reserve, and CFC are prognostic factors for death and nonfatal myocardial infarction in patients with known or suspected coronary artery disease. Importantly, after adjustment for clinical characteristics and the combined use of [ 15 O]H 2 O positron emission tomography perfusion metrics, modified CFC remained independently associated with adverse outcome., Competing Interests: Disclosures None.

Background: Positron emission tomography (PET) is the clinical gold standard for quantifying myocardial blood flow (MBF). Pericoronary adipose tissue (PCAT) attenuation may detect vascular inflammation indirectly. We examined the relationship between MBF by PET and plaque burden and PCAT on coronary CT angiography (CCTA)., Methods: This post hoc analysis of the PACIFIC trial included 208 patients with suspected coronary artery disease (CAD) who underwent [ 15 O]H 2 O PET and CCTA. Low-attenuation plaque (LAP, < 30HU), non-calcified plaque (NCP), and PCAT attenuation were measured by CCTA., Results: In 582 vessels, 211 (36.3%) had impaired per-vessel hyperemic MBF (≤ 2.30 mL/min/g). In multivariable analysis, LAP burden was independently and consistently associated with impaired hyperemic MBF (P = 0.016); over NCP burden (P = 0.997). Addition of LAP burden improved predictive performance for impaired hyperemic MBF from a model with CAD severity and calcified plaque burden (P < 0.001). There was no correlation between PCAT attenuation and hyperemic MBF (r = - 0.11), and PCAT attenuation was not associated with impaired hyperemic MBF in univariable or multivariable analysis of all vessels (P > 0.1)., Conclusion: In patients with stable CAD, LAP burden was independently associated with impaired hyperemic MBF and a stronger predictor of impaired hyperemic MBF than NCP burden. There was no association between PCAT attenuation and hyperemic MBF., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

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., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: Distinct sex-related differences exist in coronary artery plaque burden and distribution. We aimed to explore sex differences in quantitative plaque burden by coronary CT angiography (CCTA) in relation to ischemia by invasive fractional flow reserve (FFR)., Methods: This post-hoc analysis of the PACIFIC trial included 581 vessels in 203 patients (mean age 58.1 ​± ​8.7 years, 63.5% male) who underwent CCTA and per-vessel invasive FFR. Quantitative assessment of total, calcified, non-calcified, and low-density non-calcified plaque burden were performed using semiautomated software. Significant ischemia was defined as invasive FFR ≤0.8., Results: The per-vessel frequency of ischemia was higher in men than women (33.5% vs. 7.5%, p ​< ​0.001). Women had a smaller burden of all plaque subtypes (all p ​< ​0.01). There was no sex difference on total, calcified, or non-calcified plaque burdens in vessels with ischemia; only low-density non-calcified plaque burden was significantly lower in women (beta: -0.183, p ​= ​0.035). The burdens of all plaque subtypes were independently associated with ischemia in both men and women (For total plaque burden (5% increase): Men, OR: 1.15, 95%CI: 1.06-1.24, p ​= ​0.001; Women, OR: 1.96, 95%CI: 1.11-3.46, p ​= ​0.02). No significant interaction existed between sex and total plaque burden for predicting ischemia (interaction p ​= ​0.108). The addition of quantitative plaque burdens to stenosis severity and adverse plaque characteristics improved the discrimination of ischemia in both men and women., Conclusions: In symptomatic patients with suspected CAD, women have a lower CCTA-derived burden of all plaque subtypes compared to men. Quantitative plaque burden provides independent and incremental predictive value for ischemia, irrespective of sex., Competing Interests: Declaration of Competing Interest Outside of the current work, S.C., P.S., and D.D. received software royalties from Cedars-Sinai Medical Center. D.B, P.S., and D.D. hold a patent (US8885905B2 in USA and WO patent WO2011069120A1, Method and System for Plaque Characterization)., (Copyright © 2022 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Aims: Data on the warranty period of coronary computed tomography angiography (CTA) and combined coronary CTA/positron emission tomography (PET) are scarce. The present study aimed to determine the event-free (warranty) period after coronary CTA and the potential additional value of PET., Method and Results: Patients with suspected but not previously diagnosed coronary artery disease (CAD) who underwent coronary CTA and/or [15O]H2O PET were categorized based upon coronary CTA as no CAD, non-obstructive CAD, or obstructive CAD. A hyperaemic myocardial blood flow (MBF) ≤ 2.3 mL/min/g was considered abnormal. The warranty period was defined as the time for which the cumulative event rate of death and non-fatal myocardial infarction (MI) was below 5%. Of 2575 included patients (mean age 61.4 ± 9.9 years, 41% male), 1319 (51.2%) underwent coronary CTA only and 1237 (48.0%) underwent combined coronary CTA/PET. During a median follow-up of 7.0 years 163 deaths and 68 MIs occurred. The warranty period for patients with no CAD on coronary CTA was ≥10 years, whereas patients with non-obstructive CAD had a 5-year warranty period. Patients with obstructive CAD and normal hyperaemic MBF had a 2-year longer warranty period compared to patients with obstructive CAD and abnormal MBF (3 years vs. 1 year)., Conclusion: As standalone imaging, the warranty period for normal coronary CTA is ≥10 years, whereas patients with non-obstructive CAD have a warranty period of 5 years. Normal PET yielded a 2-year longer warranty period in patients with obstructive CAD., Competing Interests: Conflict of interest: J.K. has received consultancy fees from GE Healthcare and AstraZeneca and speaker fees from GE Healthcare, Bayer, Lundbeck, Boehringer Ingelheim, Pfizer, and Merck, outside of the submitted work. A.S. has received fees for consultancy or lectures from Abbott, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, and Pfizer. The remaining authors have nothing to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)