Progression of non-obstructive coronary plaque: a practical CCTA-based risk score from the PARADIGM registry.

OBJECTIVES: No clear recommendations are endorsed by the different scientific societies on the clinical use of repeat coronary computed tomography angiography (CCTA) in patients with non-obstructive coronary artery disease (CAD). This study aimed to develop and validate a practical CCTA risk score to predict medium-term disease progression in patients at a low-to-intermediate probability of CAD. METHODS: Patients were part of the Progression of AtheRosclerotic PlAque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry. Specifically, 370 (derivation cohort) and 219 (validation cohort) patients with two repeat, clinically indicated CCTA scans, non-obstructive CAD, and absence of high-risk plaque (≥ 2 high-risk features) at baseline CCTA were included. Disease progression was defined as the new occurrence of ≥ 50% stenosis and/or high-risk plaque at follow-up CCTA. RESULTS: In the derivation cohort, 104 (28%) patients experienced disease progression. The median time interval between the two CCTAs was 3.3 years (2.7-4.8). Odds ratios for disease progression derived from multivariable logistic regression were as follows: 4.59 (95% confidence interval: 1.69-12.48) for the number of plaques with spotty calcification, 3.73 (1.46-9.52) for the number of plaques with low attenuation component, 2.71 (1.62-4.50) for 25-49% stenosis severity, 1.47 (1.17-1.84) for the number of bifurcation plaques, and 1.21 (1.02-1.42) for the time between the two CCTAs. The C-statistics of the model were 0.732 (0.676-0.788) and 0.668 (0.583-0.752) in the derivation and validation cohorts, respectively. CONCLUSIONS: The new CCTA-based risk score is a simple and practical tool that can predict mid-term CAD progression in patients with known non-obstructive CAD. CLINICAL RELEVANCE STATEMENT: The clinical implementation of this new CCTA-based risk score can help promote the management of patients with non-obstructive coronary disease in terms of timing of imaging follow-up and therapeutic strategies. KEY POINTS: • No recommendations are available on the use of repeat CCTA in patients with non-obstructive CAD. • This new CCTA score predicts mid-term CAD progression in patients with non-obstructive stenosis at baseline. • This new CCTA score can help guide the clinical management of patients with non-obstructive CAD.

Ejection fraction and ventricular volumes on rubidium positron emission tomography: Validation against cardiovascular magnetic resonance.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is the non-invasive gold standard for non-invasively determining left ventricular volumes (LVVs) and ejection fraction (EF). We aimed to assess the accuracy of LVV and left ventricular ejection fraction measured by positron emission tomography (PET) as compared to CMR. METHODS: Patients who underwent both PET and CMR within 1 year were identified from prospective institutional registries. Analysis was performed to evaluate the agreement between the raw and body-surface-area-normalized left ventricular volume (LVV) and EF derived from PET vs. those derived from CMR. RESULTS: The study population consisted of 669 patients (mean age 62 ± 13 years, 65% male). The median (interquartile range [IQR]) duration between CMR and PET imaging was 36 (7-118) days. The median (IQR) EF values were 52% (38-63%) on CMR and 53% (37-65%) on PET (mean difference: 0.53% ± 9.1, P = 0.129) with a strong correlation (Spearman rho = 0.84, P < 0.001; Intraclass Correlation Coefficient 0.84, 95% confidence interval [CI]: 0.82-0.86, P < 0.001; Lin's concordance correlation coefficient was 0.844, 95% CI: 0.822 to 0.865). Results were similar with LVV, normalized LVV/EF, and in subgroups of patients with reduced EF, coronary artery disease scar, and LV hypertrophy as well as in patients with defibrillators. However, PET tended to underestimate LVV compared to CMR. CONCLUSION: Our analysis showed a strong correlation of EF and LVV by PET against a reference standard of CMR, whereas PET significantly underestimated LVV, but not EF, compared to CMR.

Integrated myocardial flow reserve (iMFR) assessment: diffuse atherosclerosis and microvascular dysfunction are more strongly associated with mortality than focally impaired perfusion.

BACKGROUND AND AIMS: Although treatment of ischemia-causing epicardial stenoses may improve symptoms of ischemia, current evidence does not suggest that revascularization improves survival. Conventional myocardial ischemia imaging does not uniquely identify diffuse atherosclerosis, microvascular dysfunction, or nonobstructive epicardial stenoses. We sought to evaluate the prognostic value of integrated myocardial flow reserve (iMFR), a novel noninvasive approach to distinguish the perfusion impact of focal atherosclerosis from diffuse coronary disease. METHODS: This study analyzed a large single-center registry of consecutive patients clinically referred for rest-stress myocardial perfusion positron emission tomography. Cox proportional hazards modeling was used to assess the association of two previously reported and two novel perfusion measures with mortality risk: global stress myocardial blood flow (MBF); global myocardial flow reserve (MFR); and two metrics derived from iMFR analysis: the extents of focal and diffusely impaired perfusion. RESULTS: In total, 6867 patients were included with a median follow-up of 3.4 years [1st-3rd quartiles, 1.9-5.0] and 1444 deaths (21%). Although all evaluated perfusion measures were independently associated with death, diffusely impaired perfusion extent (hazard ratio 2.65, 95%C.I. [2.37-2.97]) and global MFR (HR 2.29, 95%C.I. [2.08-2.52]) were consistently stronger predictors than stress MBF (HR 1.62, 95%C.I. [1.46-1.79]). Focally impaired perfusion extent (HR 1.09, 95%C.I. [1.03-1.16]) was only moderately related to mortality. Diffusely impaired perfusion extent remained a significant independent predictor of death when combined with global MFR (p < 0.0001), providing improved risk stratification (overall net reclassification improvement 0.246, 95%C.I. [0.183-0.310]). CONCLUSIONS: The extent of diffusely impaired perfusion is a strong independent and additive marker of mortality risk beyond traditional risk factors, standard perfusion imaging, and global MFR, while focally impaired perfusion is only moderately related to mortality.

The utility of beta-hydroxybutyrate in detecting myocardial glucose uptake suppression in patients undergoing inflammatory [18F]-FDG PET studies.

PURPOSE: We evaluated whether serum beta-hydroxybutyrate (BHB) can identify adequate suppression of the left ventricle (LV) among patients undergoing [18F]-fluorodeoxyglucose positron emission tomography ([18F]-FDG PET) for cardiac inflammatory/infectious studies. METHODS: Consecutive patients who underwent [18F]-FDG PET imaging were included. Serum BHB levels were measured in all patients on the day of imaging prior to injecting [18F]-FDG. Myocardial [18F]-FDG suppression was defined if [18F]-FDG uptake in the walls of myocardium, measured using standardized uptake values (SUV), was lower than the blood pool. The optimal threshold of BHB to identify myocardial suppression was based on receiver operating characteristics (ROC) in a random 30% sample of the study population (derivation cohort) and tested in the remaining 70% of sample (validation cohort). RESULTS: A total of 256 images from 220 patients were included. Patients with sufficient LV suppression had significantly higher BHB levels compared to those with non-suppressed myocardium (median (IQR) BHB 0.6 (0.3-0.8) vs. 0.2 (0.2-0.3) mmol/l, p < 0.001, respectively). BHB level ≥ 0.335 mmol/l had a sensitivity of 84.90% and a specificity of 92.60% to identify adequate LV suppression in the validation cohort. All patients (100%) with BHB ≥ 0.41 mmol/l had adequate myocardial suppression compared to 29.63% of patients with BHB ≤ 0.20 mmol/l. CONCLUSION: Serum BHB level can be used at the point of care to identify sufficient LV suppression in patients undergoing [18F]-FDG PET cardiac inflammatory/infectious studies. Central illustration (image to the right) shows representative cases of patient images and BHB and, in the image to the left, shows the sensitivity and specificity to identify left myocardial suppression using BHB in validation group.

Integrated myocardial flow reserve (iMFR) assessment: optimized PET blood flow quantification for diagnosis of coronary artery disease.

PURPOSE: Distinguishing obstructive epicardial coronary artery disease (CAD) from microvascular dysfunction and diffuse atherosclerosis would be of immense benefit clinically. However, quantitative measures of absolute myocardial blood flow (MBF) integrate the effects of focal epicardial stenosis, diffuse atherosclerosis, and microvascular dysfunction. In this study, MFR and relative perfusion quantification were combined to create integrated MFR (iMFR) which was evaluated using data from a large clinical registry and an international multi-center trial and validated against invasive coronary angiography (ICA). METHODS: This study included 1,044 clinical patients referred for 82Rb rest/stress positron emission tomography myocardial perfusion imaging and ICA, along with 231 patients from the Flurpiridaz 301 trial (clinicaltrials.gov NCT01347710). MFR and relative perfusion quantification were combined to create an iMFR map. The incremental value of iMFR was evaluated for diagnosis of obstructive stenosis, adjusted for patient demographics and pre-test probability of CAD. Models for high-risk anatomy (left main or three-vessel disease) were also constructed. RESULTS: iMFR parameters of focally impaired perfusion resulted in best fitting diagnostic models. Receiver-operating characteristic analysis showed a slight improvement compared to standard quantitative perfusion approaches (AUC 0.824 vs. 0.809). Focally impaired perfusion was also associated with high-risk CAD anatomy (OR 1.40 for extent, and OR 2.40 for decreasing mean MFR). Diffusely impaired perfusion was associated with lower likelihood of obstructive CAD, and, in the absence of transient ischemic dilation (TID), with lower likelihood of high-risk CAD anatomy. CONCLUSIONS: Focally impaired perfusion extent derived from iMFR assessment is a powerful incremental predictor of obstructive CAD while diffusely impaired perfusion extent can help rule out obstructive and high-risk CAD in the absence of TID.

Incremental prognostic value of positron emission tomography derived left ventricular mass.

BACKGROUND: 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). METHODS: 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). RESULTS: 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. CONCLUSION: Our analysis shows that LVM provides no independent and incremental prognostic value over MFR and clinical variables.

Splenic switch-off in regadenoson 82Rb-PET myocardial perfusion imaging: assessment of clinical utility.

BACKGROUND: Splenic switch-off (SSO) is a phenomenon describing a decrease in splenic radiotracer uptake after vasodilatory stress. We aimed to assess the diagnostic utility of regadenoson-induced SSO. METHODS: We included consecutive patients who had clinically indicated Regadenoson Rb-82 PET-MPI for suspected CAD. This derivation cohort (no perfusion defects and myocardial flow reserves (MFR) ≥ 2) was used to calculate the splenic response ratio (SRR). The validation cohort was defined as patients who underwent both PET-MPI studies and invasive coronary angiography (ICA). RESULTS: The derivation cohort (n = 100, 57.4 ± 11.6 years, 77% female) showed a decrease in splenic uptake from rest to stress (79.9 ± 16.8 kBq⋅mL vs 69.1 ± 16.2 kBq⋅mL, P < .001). From the validation cohort (n = 315, 66.3 ± 10.4 years, 67% male), 28% (via SRR = 0.88) and 15% (visually) were classified as splenic non-responders. MFR was lower in non-responders (SRR; 1.55 ± 0.65 vs 1.76 ± 0.78, P = .02 and visually; 1.18 ± 0.33 vs 1.79 ± 0.77, P < .001). Based on ICA, non-responders were more likely to note obstructive epicardial disease with normal PET scans especially in patients with MFR < 1.5 (SRR; 61% vs 34% P = .05 and visually; 68% vs 33%, P = .01). CONCLUSION: Lack of splenic response based on visual or quantitative assessment of SSO may be used to identify an inadequate vasodilatory response.

Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Mortality Among COVID-19 Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are known to increase the expression of angiotensin converting enzyme 2 receptor, which has been shown to be the receptor for the acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2). AREAS OF UNCERTAINTY: Based on these observations, speculations raised the concerns that ACEIs/ARBs users would be more susceptible to SARS-CoV-2 infection and would be at higher risk for severe COVID-19 disease and death. Therefore, we systematically reviewed the literature and performed a meta-analysis of the association between prior use of ACEIs and ARBs and mortality due to COVID-19 disease. DATA SOURCES: A comprehensive search of several databases from November 2019 to June 18, 2020 was conducted. The databases included Ovid MEDLINE(R) and Epub Ahead of Print, In-Process and Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, and Scopus. Medrxiv.org was also searched for unpublished data. THERAPEUTIC ADVANCES: Nine studies with a total of 18,833 patients infected with SARS-CoV-2 met our eligibility criteria. Prior use of ACEIs and/or ARBs was associated with reduced mortality among SARS-CoV-2-infected patients, with a pooled adjusted relative risk (aRR) from 6 studies of 0.63, 95% confidence interval (CI) (0.42-0.94) (I 2 = 65%). Three studies reported separately on ACEIs or ARBs and their association with survival among SARS-CoV-2-infected patients, with a pooled adjusted relative risk of 0.78, 95% CI (0.58-1.04) (I 2 = 0%) and 0.97, 95% CI (0.73-1.30) (I 2 = 0%) respectively. The results of sensitivity analyses were consistent with the main analysis. CONCLUSION: Our meta-analysis suggests that use of ACEIs/ARBs is associated with a decreased risk of death among SARS-CoV-2-infected patients. This finding provides a reassurance to the public not to stop prescribed ACEIs/ARBs because of fear of severe COVID-19.

Advances in Digital PET Technology and Its Potential Impact on Myocardial Perfusion and Blood Flow Quantification.

PURPOSE OF REVIEW: In this review, we explore the development of digital PET scanners and describe the mechanism by which they work. We dive into some technical details on what differentiates a digital PET from a conventional PET scanner and how such differences lead to better imaging characteristics. Additionally, we summarize the available evidence on the improvements in the images acquired by digital PET as well as the remaining pitfalls. Finally, we report the comparative studies available on how digital PET compares to conventional PET, particularly in the quantification of coronary blood flow. RECENT FINDINGS: The advent of digital PET offers high sensitivity and time-of-flight (TOF), which allow lower activity and scan times, with much less risk of detector saturation. This allows faster patient throughput, scanning more patients per generator, and acquiring more consistent image quality across patients. The higher sensitivity captures more of the potential artifacts, particularly motion-related ones, which presents a current challenge that still needs to be tackled. The digital silicon photomultiplier (SiPM) positron emission tomography (PET) machine has been an important development in the technological advancements of non-invasive nuclear cardiovascular imaging. It has enhanced the utility for PET myocardial perfusion imaging (MPI) and myocardial blood flow (MBF) quantification.

Improved cardiorespiratory fitness is associated with lower incident ischemic stroke risk: Henry Ford FIT project.

BACKGROUND: Change in cardiorespiratory fitness (CRF) modulates vascular disease risk; however, it's unclear if this adds further prognostic information, particularly for ischemic stroke. The objective of this analysis is to describe the association between the change in CRF over time and subsequent incident ischemic stroke. METHODS: This is a retrospective, longitudinal, observational cohort study of 9,646 patients (age=55±11 years; 41% women; 25% black) who completed 2 clinically indicated exercise tests (> 12 months apart) and were free of any stroke at the time of test 2. CRF was expressed as metabolic-equivalents-of-task (METs). Incident ischemic stroke was identified using ICD codes. The adjusted hazard ratio (aHR) was determined for risk of ischemic stroke associated with change in CRF. RESULTS: Mean time between tests was 3.7 years (IQR, 2.2, 6.0). During a median of 5.0 years (IQR, 2.7, 7.6 y) of follow-up, there were 873 (9.1%) ischemic stroke events. Each 1 MET increase between tests was associated with a 9% lower ischemic stroke risk (aHR 0.91 [0.88-0.94]; n = 9.646). There was an interaction effect by baseline CRF category, but not for sex or race. A sensitivity analysis which removed those who experienced an incident diagnosis known to be associated with an increased risk of ischemic vascular disease, validated our primary findings (aHR 0.91 [0.88, 0.95]; n= 6,943). CONCLUSIONS: Improvement in CRF over time is independently and inversely associated with a lower risk of ischemic stroke. Encouragement of regular exercise focused on improving CRF may reduce ischemic stroke risk.

Prognostic Significance of Nonobstructive Left Main Coronary Artery Disease in Patients With and Without Diabetes: Long-Term Outcomes From the CONFIRM Registry.

BACKGROUND: Prognostic significance of non-obstructive left main (LM) disease was recently reported. However, the influence of diabetes mellitus (DM) on event rates in patients with and without non-obstructive LM disease is not well-known. METHODS: We evaluated 27,252 patients undergoing coronary computed tomographic angiography from the COroNary CT Angiography Evaluation For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) Registry. Cumulative long-term incidence of all-cause mortality (ACM) was assessed between DM and non-DM patients by normal or non-obstructive LM disease (1-49% stenosis). RESULTS: The mean age of the study population was 57.6±12.6 years. Of the 27,252 patients, 4,434 (16%) patients had DM. A total of 899 (3%) deaths occurred during the follow-up of 3.6±1.9. years. Compared to patients with normal LM, those with non-obstructive LM had more pronounced overall coronary atherosclerosis and more cardiovascular risk factors. After clinical risk factors, segment involvement score, and stenosis severity adjustment, compared to patients without DM and normal LM, patients with DM were associated with increased ACM regardless of normal (HR 1.48, 95% CI 1.22-1.78, p<0.001) or non-obstructive LM (HR 1.46, 95% CI 1.04-2.04, p=0.029), while nonobstructive LM disease was not associated with increased ACM in patients without DM (HR 0.85, 95% CI 0.67-1.07, p=0.165) and there was no significant interaction between DM and LM status (HR 1.03, 95% CI 0.69-1.54, p=0.879). CONCLUSION: From the CONFIRM registry, we demonstrated that DM was associated with increased ACM. However, the presence of non-obstructive LM was not an independent risk marker of ACM, and there was no significant interaction between DM and non-obstructive LM disease for ACM.

Cardiovascular magnetic resonance for suspected cardiac amyloidosis: where are we now?

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.

99mTechnetium-labeled cardiac scintigraphy for suspected amyloidosis: a review of current and future directions.

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, and nuclear imaging. Technetium (Tc)-labeled cardiac scintigraphy has witnessed a resurgence in its application for the workup of CA. Advancements in disease-modifying therapies have fueled the rapid adoption of cardiac scintigraphy using bone tracers and the need for transformative novel studies. The goal of this review is to present diagnostic utility, currently recommended protocols, as well as a glimpse into the rapid evolution of Tc-labeled cardiac scintigraphy in the diagnosis of CA.

The utility of positron emission tomography in cardiac amyloidosis.

Cardiac amyloidosis, characterized by progressive restrictive cardiomyopathy, presents unusual diagnostic challenges. Conventional cardiac scintigraphy has shown limited utility in the quantification of disease burden and serial follow-up of cardiac amyloidosis. The advent of specialized positron emission tomography with specific amyloid-binding radiotracers has the potential to change currently employed diagnostic algorithms for the imaging of cardiac amyloidosis. This review aims to discuss the diagnostic utility of amyloid-binding radiotracers, including Pittsburg compound B, florbetapir, florbetapan, and sodium fluoride. These tracers have promising potential for the early detection of the particular type of cardiac amyloidosis, pursuing relevant medical intervention, assessing amyloid burden, monitoring treatment response, and overall prognostication.

Change in positron emission tomography perfusion imaging quality with a data-driven motion correction algorithm.

INTRODUCTION: Cardiac motion frequently reduces the interpretability of PET images. This study utilized a prototype data-driven motion correction (DDMC) algorithm to generate corrected images and compare DDMC images with non-corrected images (NMC) to evaluate image quality and change of perfusion defect size and severity. METHODS: Rest and stress images with NMC and DDMC from 40 consecutive patients with motion were rated by 2 blinded investigators on a 4-point visual ordinal scale (0: minimal motion; 1: mild motion; 2: moderate motion; 3: severe motion/uninterpretable). Motion was also quantified using Dwell Fraction, which is the fraction of time the motion vector shows the heart to be within 6 mm of the corrected position and was derived from listmode data of NMC images. RESULTS: Minimal motion was seen in 15% of patients, while 40%, 30%, and 15% of patients had mild moderate and severe motion, respectively. All corrected images showed an improvement in quality and were interpretable after processing. This was confirmed by a significant correlation (Spearman's correlation coefficient 0.626, P < .001) between machine measurement of motion quantification and physician interpretation. CONCLUSION: The novel DDMC algorithm improved quality of cardiac PET images with motion. Correlation between machine measurement of motion quantification and physician interpretation was significant.

Left ventricular mass on positron emission tomography: Validation against cardiovascular magnetic resonance.

BACKGROUND: Left ventricular hypertrophy (LVH) is an important clinical finding that is independently associated with mortality and cardiovascular events. We aimed to assess the interstudy variability of LV mass quantitation between PET and CMR. METHODS: Patients who underwent both PET and CMR within 1 year were identified from prospective institutional registries. LV mass on PET was compared against LV mass on CMR using several statistical measures of agreement. RESULTS: A total of 105 patients (mean age 60 ± 14 years, 67.6% male) were included. The median (interquartile range, IQR) duration between CMR and PET was 47 (11-154) days. The median (IQR) LV mass values were 168.0 g (126.0-202.0) on CMR and 174.0 g (150.0-212.0) with PET (absolute mean difference 29.42 ± 25.3). There was a good correlation (Spearman ρ = 0.81, P < 0.001; Intraclass Correlation Coefficient 0.78, 95% CI 0.70-0.85, P < 0.001) with moderate limits of agreement (95% limits of agreement - 63.78 to 83.7.) Results were consistent, albeit with moderate correlation, in subgroups of patients with LVH, in patients with myocardial infarction, in patients with LV ejection fraction < 50%, and those with limited image quality. LV mass on PET tended to be underestimated at high values compared to CMR. CONCLUSION: We demonstrate good correlation and reproducibility of LV mass quantitation by PET against the reference standard of CMR across a wide range of normal and diseased hearts with a tendency of PET to underestimate mass at higher mass values.

Outcomes of patients with moderate-to-severe Ischemia excluded from the ischemia trial.

BACKGROUND: The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial showed no difference in outcomes between medical therapy vs coronary revascularization in the management of patients with stable coronary artery disease. We aimed to determine the percentage of patients with at least moderate ischemia that would have been eligible for enrollment and evaluate the outcomes of those who would not. METHODS: Consecutive patients who underwent cardiac single-photon emission computed tomography (SPECT) between April 2016 and September 2019 were identified and all-cause mortality was determined. RESULTS: There were a total of 1508 patients (mean age 67 ± 11.6 years, 69.5% males) with any perfusion defect on SPECT. Patients had a high prevalence of cardiac risk factors (73.4% with hypertension and 54.4% with diabetes mellitus.) Nearly half (709, 47%) had moderate-to-severe ischemia but over two-thirds (479/709, 66.3%) had at least one ISCHEMIA trial exclusion criteria. Patients meeting ISCHEMIA enrollment criteria had a significantly lower all-cause mortality than those who would have been excluded (3.91% vs. 11.3%, respectively, P < .001). CONCLUSION: Our results show that ISCHEMIA selected a relatively small subset of lower risk patients among the larger higher risk group of patients with moderate-to-severe ischemia typical to most cardiology centers.

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

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

Prognostic value of exercise capacity in incident diabetes: a country with high prevalence of diabetes.

BACKGROUND: Diabetes Mellitus (DM) is a fast-growing health problem that imposes an enormous economic burden. Several studies demonstrated the association between physical inactivity and predicting the incidence of diabetes. However, these prediction models have limited validation locally. Therefore, we aim to explore the predictive value of exercise capacity in the incidence of diabetes within a high diabetes prevalence population. METHODOLOGY: A retrospective cohort study including consecutive patients free of diabetes who underwent clinically indicated treadmill stress testing. Diabetic patients at baseline or patients younger than 18 years of age were excluded. Incident diabetes was defined as an established clinical diagnosis post-exercise testing date. The predictive value of exercise capacity was examined using Harrell's c-index, net reclassification index (NRI), and integrated discrimination index (IDI). RESULTS: A total of 8,722 participants (mean age 46 ± 12 years, 66.3% were men) were free of diabetes at baseline. Over a median follow-up period of 5.24 (2.17-8.78) years, there were 2,280 (≈ 26%) new cases of diabetes. In a multivariate model adjusted for conventional risk factors, we found a 12% reduction in the risk of incident diabetes for each METs achieved (HR, 0.9; 95% CI, 0.88-0.92; P < 0.001). Using Cox regression, exercise capacity improved the prediction ability beyond the conventional risk factors (AUC = 0.62 to 0.66 and c-index = 0.62 to 0.68). CONCLUSION: Exercise capacity improved the overall predictability of diabetes. Patients with reduced exercise capacity are at high risk for developing incidence diabetes. Improvement of both physical activity and functional capacity represents a preventive measure for the general population.

Diagnostic Accuracy of FDG PET for the Identification of Vascular Graft Infection.

BACKGROUND: Fluorodeoxyglucose (FDG) positron emission tomography (FDG PET/CT) can be used to identify and localize infection in patients with vascular graft infections (VGI). We aimed to evaluate the diagnostic accuracy of 18F-FDG PET/CT by defining thresholds for standardized uptake value (SUV) and tissue-to-background ratio (TBR) that would accurately identify the presence of vascular graft infection. METHODS: Patients with suspected VGI were prospectively recruited and underwent 18F-FDG PET/CT scans. Diagnosis was based on clinical, laboratory and radiologic findings, and blinded to the results of the PET/CT scan. Receiver operator characteristics (ROC) curve analysis was done to determine optimal thresholds for SUV and TBR. RESULTS: Our final cohort consisted of 28 patients with suspected VGI (mean ± SD age 67 ± 10 years, 61% men), of which 15 patients (54%) had definitive VGI. The cohort included 61% prosthetics grafts and 39% stent-grafts. The type of graft included in this study were biologic (4%), Dacron (64%) and Polytetrafluoroethylene (32%). The location of the implanted grafts was aortic (54%) and peripheral arterial reconstruction (46%). The location of the peripheral graft was 77% in lower extremity and 23% in the upper extremity (arterio-venous grafts for dialysis access). Using ROC analysis, SUV max of 4.5, SUV mean of 3.7, and a TBR of 1.6 gave the best balance between sensitivity and specificity (93%/92%, 100%/92% and 93%/92%, respectively). All thresholds had an area under the curve ≥0.93 and correct reclassification rate ≥93%. CONCLUSIONS: Our data suggests that FDG PET/CT can be used to reliably and accurately diagnose VGI. The dual anatomic-physiologic information from FDG PET/CT can complement clinical diagnosis particularly in uncertain cases.