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Aims We aimed to assess the incremental prognostic value of positron emission tomography (PET)-derived myocardial flow reserve (MFR) among patients with diabetes and those without diabetes. Methods and results Consecutive patients with clinically indicated PET MPI for suspected or established coronary artery disease (CAD) were included. Myocardial blood flow (MBF) in mL/min/g was obtained from dynamic images at rest and stress, while MFR was calculated as the ratio of stress to rest MBF. Patients were followed from the date of PET imaging for the occurrence of the primary outcome (composite of all-cause death, myocardial infarction, and un-planned percutaneous coronary intervention/coronary artery bypass graft occurring more than 90 days after imaging). The final cohort consisted of 6019 patients (63% with diabetes) (mean age 61 ± 11 years, 45% female, 55% obese, 76% hypertensive, and 62% dyslipidaemia). Over half (53%) of the patients had an impaired MFR ( Conclusion PET-derived MFR has a strong independent and incremental prognostic role in patients with diabetes and those without diabetes.

Positron Emission Tomography (PET) Myocardial Perfusion Imaging (MPI) is a robust diagnostic and prognostic test in patients with suspected or known coronary artery disease (CAD). We aimed to assess the incremental prognostic value of myocardial flow reserve (MFR) using the latest generation of digital PET scanners.Consecutive patients with clinically indicated PET MPI for suspected or known CAD were included. Myocardial blood flow (MBF) in ml/min/g was obtained from dynamic images at rest and peak hyperemia, and the myocardial flow reserve (MFR) was calculated as the ratio of stress to rest MBF. Patients were followed from the date of PET imaging for the occurrence of the primary outcome (composite of all-cause death, myocardial infarction, and Percutaneous Coronary Intervention or Coronary Artery Bypass Graft occurring90 days after imaging). Nested multivariable Cox regression models were used to assess the incremental prognostic role of MFR over traditional risk factors and PET relative perfusion parameters.The final cohort consisted of 3534 patients (mean age 67 ± 12 years, 48% female, 67% Caucasian, 53% obese, 55% hypertension, 32% diabetes, 42% dyslipidemia). During a median follow-up of 8.5 (3.0-15.4) months, 229 patients (6.5%, 6.4 per 1000 person-years) experienced the primary outcome. In nested multivariable Cox models, impaired MFR (MFR 2) was significantly associated with the primary outcome (HR 2.9, 95% CI 2.0-4.1, p 0.001) and significantly improved discrimination (Harrell's C 0.77, p = 0.002).MFR derived from digital PET scanners has an independent and incremental prognostic role in patients with suspected or known CAD.

Coronary computed tomography (CT) angiography (CCTA) is increasingly recognized for diagnosing obstructive coronary artery disease (CAD) among patients presenting with chest pain. In this review, we summarize the utility of CCTA to determine luminal stenosis and identifying coronary plaques with high-risk features. We review different scoring systems that can quantify total plaque burden including how artificial intelligence can facilitate more detailed plaque assessment. We discuss how CCTA can also be used to detect the hemodynamic significance of CAD lesions (fractional flow reserve CT and CT perfusion) and also local factors outside the vessel wall that may predispose to plaque rupture (fat attenuation index and wall shear stress). We conclude with technological advances in imaging acquisition using photon counting CT and post-image processing techniques especially those that can mitigate blooming artifacts.

Exercise capacity (EC) is inversely related to the risk of cardiovascular disease and incident heart failure (HF) in healthy subjects. However, there are no present studies that exclusively evaluate EC and the risk of incident HF in patients with known coronary heart disease (CHD). We aimed to determine the relation between EC and incident HF in patients with an established clinical diagnosis of CHD. We retrospectively identified 8,387 patients (age 61 ± 12 years; 30% women; 33% non-White) with a history of myocardial infarction (MI) or coronary revascularization procedure and no history of HF at the time of a clinically indicated exercise stress test completed between 1991 and 2009. EC was quantified in metabolic equivalents of task (METs) estimated from treadmill testing. Incident HF was identified through June 2010 from administrative databases based on ≥3 encounters with International Classification of Diseases, Ninth Revision 428.x. Cox regression analysis was used to evaluate the risk of incident HF associated with METs. Covariates included age; gender; race; hypertension, diabetes, hyperlipidemia, smoking, and MI; medications for CHD and lung diseases; and clinical indication for treadmill testing. During a median follow-up of 8.2 years (interquartile range 4.7 to 12.4 years) after the exercise test, 23% of the cohort experienced a new HF diagnosis. Lower EC categories were associated with higher HF incidence compared with METs ≥12, with nearly fourfold greater adjusted risk among patients with METslt;6. Per unit increase in METs of EC was associated with a 12% lower adjusted risk for HF. There was no significant interaction based on race (p = 0.06), gender (p = 0.88), age ≤61 years (p = 0.60), history of MI (p = 0.31), or diabetes (p = 0.38). This study reveals that among men and women with CHD and no history of HF, EC is independently and inversely related to the risk of future HF.

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.

Left ventricular hypertrophy has been shown to be an independent predictor of outcomes in patients with coronary artery disease (CAD). We aimed to determine the incremental prognostic value of positron emission tomography (PET) derived left ventricular mass (LVM) to clinical variables and myocardial flow reserve (MFR).We included consecutive patients who had clinically indicated PET myocardial perfusion imaging for suspected or established CAD. Patients were followed from the date of PET imaging for major adverse cardiovascular events (MACE, inclusive of all-cause death, non-fatal myocardial infarction, and percutaneous coronary intervention/coronary artery bypass grafting 90 days after imaging).A total of 2357 patients underwent PET MPI during the study period (47% female, mean age 66 ± 12 years, 87% hypertensive, 47% diabetic, 79% dyslipidemia). After a mean follow-up of 11.6 ± 6.6 months, 141 patients (6.0%, 5.1 per 1000 person-year) experienced MACE (86 D/24 MI/39 PCI/9 CABG). In nested multivariable Cox models, LVM was not independently associated with outcomes (HR 1.00, P = .157) and had no incremental prognostic value (C index: 0.75, P = .571) over MFR and clinical variables.Our analysis shows that LVM provides no independent and incremental prognostic value over MFR and clinical variables.

Coronary computed tomographic angiography (CCTA) and Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) provide comprehensive anatomic and functional assessment of the coronary arteries useful in the diagnosis and prognosis of patients with coronary artery disease (CAD). We aimed to assess the incremental prognostic role of SPECT physiologic assessment to CCTA in patients with suspected CAD.Consecutive patients with suspected CAD undergoing clinically indicated CCTA within 180 days of undergoing SPECT were included. Patients were followed for major adverse cardiovascular events (MACE, inclusive of all-cause death, non-fatal myocardial infarction, and percutaneous coronary intervention or coronary artery bypass grafting 90-days after imaging test.) RESULTS: The cohort consisted of 956 patients (mean age 61.1 ± 14.2 years, 54% men, 89% hypertension, 81% diabetes, 84% dyslipidemia). Obstructive stenosis was found in 14% of patients, while scar (fixed perfusion defect), ischemia and left ventricular ejection fraction40% were found in 17, 14 and 9% of patients, respectively. In nested multivariable cox regression models, perfusion and left ventricular function when added to a model with CCTA obstructive stenosis significantly improved model risk prediction (Harrell's C = 0.73, p = 0.037) and risk reclassification on a continuous scale (P 0.001).We have shown that a combined assessment of perfusion burden and left ventricular function added incremental value over and above a CCTA based anatomic assessment in patients with suspected CAD.

Aims Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with endothelial dysfunction. We aimed to determine the effects of prior coronavirus disease 2019 (COVID-19) on the coronary microvasculature accounting for time from COVID-19, disease severity, SARS-CoV-2 variants, and in subgroups of patients with diabetes and those with no known coronary artery disease. Methods and results Cases consisted of patients with previous COVID-19 who had clinically indicated positron emission tomography (PET) imaging and were matched 1:3 on clinical and cardiovascular risk factors to controls having no prior infection. Myocardial flow reserve (MFR) was calculated as the ratio of stress to rest myocardial blood flow (MBF) in mL/min/g of the left ventricle. Comparisons between cases and controls were made for the odds and prevalence of impaired MFR (MFR < 2). We included 271 cases matched to 815 controls (mean ± SD age 65 ± 12 years, 52% men). The median (inter-quartile range) number of days between COVID-19 infection and PET imaging was 174 (58–338) days. Patients with prior COVID-19 had a statistically significant higher odds of MFR Conclusion The prevalence of impaired MFR is similar by duration of time from infection up to 1 year and SARS-CoV-2 variants, but significantly differs by severity of infection.

Cardiac amyloidosis (CA) is an underdiagnosed form of restrictive cardiomyopathy leading to a rapid progression into heart failure. Evaluation of CA requires a multimodality approach making use of echocardiography, cardiac magnetic imaging (CMR), and nuclear imaging. With superior tissue characterization, high-resolution imaging, and precise cardiac assessment, CMR has emerged as a versatile tool in the workup of cardiac amyloidosis with a wide array of parameters both visual and quantitative. This includes late gadolinium enhancement patterns, T1/T2 mapping, and extracellular volume (ECV) measurement providing robust diagnostic accuracies, patient stratification, and prognostication. Recent advancements have introduced new measures able to identify early disease, track disease progression, and response to therapy positioning CMR as an instrumental imaging modality in the era of rising interest in CA screening and emerging effective therapies.

The aim of this study was to compare the incremental prognostic value of coronary computed tomography (CT) angiography (CCTA)-derived machine learning fractional flow reserve CT (ML-FFRct) versus that of ischemia detected on single-photon emission-computed tomography (SPECT) myocardial perfusion imaging (MPI) on incident cardiovascular outcomes.SPECT MPI and ML-FFRct are noninvasive tools that can assess the hemodynamic significance of coronary atherosclerotic disease.We studied a retrospective cohort of consecutive patients who underwent clinically indicated CCTA and SPECT MPI. ML-FFRct was computed using a ML prototype. The primary outcome was all-cause mortality and nonfatal myocardial infarction (D/MI), and the secondary outcome was D/MI and unplanned revascularization, percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) occurring more than 90 days postimaging. Multiple nested multivariate cox regression was used to model a scenario wherein an initial anatomical assessment was followed by a functional assessment.A total of 471 patients (mean age: 64 ± 13 year; 53% males) were included. Comorbidities were prevalent (78% hypertension, 66% diabetes, 81% dyslipidemia). ML-FFRct was 0.8 in at least 1 proximal/midsegment was present in 41.6% of patients, and ischemia on MPI was present in 13.8%. After a median follow-up of 18 months, 7% of patients (n = 33) experienced D/MI. On multivariate Cox proportional analysis, the presence of ischemia on MPI but not ML-FFRct significantly predicted D/MI (HR: 2.3; 95% CI: 1.0-5.0; P = 0.047; or HR: 0.7; 95% CI: 0.3-1.4; P = 0.306 respectively) when added to CCTA obstructive stenosis. Furthermore, the model with SPECT ischemia had higher global chi-square result and significantly improved reclassification. Results were similar using the secondary outcome and on several sensitivity analyses.In a high-risk patient cohort, SPECT MPI but not ML-FFRct adds independent and incremental prognostic information to CCTA-based anatomical assessment and clinical risk factors in predicting incident outcomes.

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.

BACKGROUND AND AIMS: We aimed to identify predictors of change in direct measures of coronary artery calcium (CAC) volume and density in South Asian participants. METHODS: We used data from participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study with prevalent CAC and direct measures of CAC by serial computed tomography (CT) exams (2010–2013, 2016–2018). We examined the distribution of incident CAC volume and peak density, as well as progression and identified risk factors for progression of change in volume and density in multivariable models. RESULTS: The study cohort consisted of 102 participants with incident CAC and 285 with CAC progression. CAC volume and density were highest, and incident CAC was most common in the left anterior descending artery (LAD). The greatest progression in volume was in the right coronary artery and the greatest change in density was in the left main. In linear regression models for CAC progression adjusted for baseline density, volume, risk factors, smoking (β +190.1, p = 0.02), baseline volume (β +0.24 per mm(3), p < 0.01), and scan interval (β +0.15 per day, p = 0.01) were associated with change in total volume whereas Lp(a) (β +0.81 per mg/dL, p = 0.03), exercise (β +0.19 per 10 MET-min/week, p = 0.01), and baseline volume (β +0.15 per mm(3), p < 0.01) and density (β −0.55 per unit, p < 0.01) were associated with change in total density. CONCLUSIONS: In this South Asian cohort, smoking was associated with CAC volume progression, while Lp(a) and exercise were associated with progression of peak CAC density.

The aim of this analysis is to examine the incremental prognostic value of coronary artery calcium (CAC) score and myocardial flow reserve (MFR) in patients with suspected coronary artery disease (CAD) undergoing positron emission tomography (PET) myocardial perfusion imaging (MPI).Advances in cardiac PET and computed tomography imaging enabled the simultaneous acquisition of anatomic and physiological data for patients suspected of CAD.Consecutive patients who underwent PET MPI and CAC score calculation at King Abdulaziz Cardiac Center, Riyadh, Saudi Arabia, between May 2011 and May 2018 were included in the study. MPI and CAC images were obtained in the same setting. The primary endpoint of the study was a composite of cardiac death and nonfatal myocardial infarction. Cox proportional hazard regression was used to assess the incremental prognostic value of CAC and MFR by sequentially adding the variables to a model that included clinical and PET variables.A total of 4,008 patients (mean age 59.7 ± 11.6 years, 55% women) were included in the analysis. Risk factors were prevalent (77.6% hypertension, 58.1% diabetes). In total, 35.9% of the cohort had CAC of 0, 16.5% had CAC ≥400, and 43.9% had MFR 2. Over a median follow up of 1.9 years, 130 (3.2%) patients had cardiac death/nonfatal myocardial infarction. CAC and MFR score added incremental prognostic value over clinical and perfusion variables (base model: c-index 0.8137; Akaike information criterion [AIC]: 1,865.877; p = 0.0011; CAC model: c-index = 0.8330; AIC: 1,850.810; p = 0.045 vs. base model; MFR model: c-index = 0.8279; AIC: 1,859.235; p = 0.024). Combining CAC and MFR did not enhance risk prediction (c-index = 0.8435; AIC: 1,846.334; p = 0.074 vs. MFR model; p = 0.21 vs. CAC model.) CONCLUSIONS: In this large cohort of patients referred for PET MPI, both CAC and MFR independently added incremental prognostic value over clinical and MPI variables. Although combining both may have synergetic prognostic effect, this relation was not shown in multivariable model of this analysis.

Acute chest pain is a common presentation in patients with COVID-19. Although noninvasive cardiac imaging modalities continue to be important cornerstones of management, the pandemic has brought forth difficult and unprecedented challenges in the provision of timely care while ensuring the safety of patients and providers. Clinical practice has adapted to these challenges, with several recommendations and societal guidelines emerging on the appropriate use of imaging modalities. In this review, we summarize the current evidence base on the use of noninvasive cardiac imaging modalities in COVID-19 patients with acute chest pain, with a focus on acute coronary syndromes.

Objectives This study sought to investigate the impact of low tube voltage scanning heterogeneity of coronary luminal attenuation on plaque quantification and characterization with coronary computed tomography angiography (CCTA). Background The impact of low tube voltage and coronary luminal attenuation on quantitative coronary plaque remains uncertain. Methods A total of 1,236 consecutive patients (age: 60 ± 9 years; 41% female) who underwent serial CCTA at an interval of ≥2 years were included from an international registry. Patients with prior revascularization or nonanalyzable coronary CTAs were excluded. Total coronary plaque volume was assessed and subclassified based on specific Hounsfield unit (HU) threshold: necrotic core, fibrofatty plaque, and fibrous plaque and dense calcium. Luminal attenuation was measured in the aorta. Results With increasing luminal HU ( 500 HU), percent calcified plaque was increased (16%, 27%, and 40% in the median; P Conclusions Low tube voltage usage affected plaque morphology, mainly through an increase in luminal HU with a resultant increase in calcified plaque and a reduction in fibrofatty and necrotic core. These findings should be considered as CCTA-based plaque measures are being used to guide medical management and, in particular, when being used as a measure of treatment response. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411 )

Objectives\udThe aim of this study was to define the variability of maximal wall thickness (MWT) measurements across modalities and predict its impact on care in patients with hypertrophic cardiomyopathy (HCM).\ud\udBackground\udLeft ventricular MWT measured by echocardiography or cardiovascular magnetic resonance (CMR) contributes to the diagnosis of HCM, stratifies risk, and guides key decisions, including whether to place an implantable cardioverter-defibrillator (ICD).\ud\udMethods\udA 20-center global network provided paired echocardiographic and CMR data sets from patients with HCM, from which 17 paired data sets of the highest quality were selected. These were presented as 7 randomly ordered pairs (at 6 cardiac conferences) to experienced readers who report HCM imaging in their daily practice, and their MWT caliper measurements were captured. The impact of measurement variability on ICD insertion decisions was estimated in 769 separately recruited multicenter patients with HCM using the European Society of Cardiology algorithm for 5-year risk for sudden cardiac death.\ud\udResults\udMWT analysis was completed by 70 readers (from 6 continents; 91% with >5 years’ experience). Seventy-nine percent and 68% scored echocardiographic and CMR image quality as excellent. For both modalities (echocardiographic and then CMR results), intramodality inter-reader MWT percentage variability was large (range –59% to 117% [SD ±20%] and –61% to 52% [SD ±11%], respectively). Agreement between modalities was low (SE of measurement 4.8 mm; 95% CI 4.3 mm-5.2 mm; r = 0.56 [modest correlation]). In the multicenter HCM cohort, this estimated echocardiographic MWT percentage variability (±20%) applied to the European Society of Cardiology algorithm reclassified risk in 19.5% of patients, which would have led to inappropriate ICD decision making in 1 in 7 patients with HCM (8.7% would have had ICD placement recommended despite potential low risk, and 6.8% would not have had ICD placement recommended despite intermediate or high risk).\ud\udConclusions\udUsing the best available images and experienced readers, MWT as a biomarker in HCM has a high degree of inter-reader variability and should be applied with caution as part of decision making for ICD insertion. Better standardization efforts in HCM recommendations by current governing societies are needed to improve clinical decision making in patients with HCM.