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.

Patient-level explainable machine learning to predict major adverse cardiovascular events from SPECT MPI and CCTA imaging.

BACKGROUND: Machine learning (ML) has shown promise in improving the risk prediction in non-invasive cardiovascular imaging, including SPECT MPI and coronary CT angiography. However, most algorithms used remain black boxes to clinicians in how they compute their predictions. Furthermore, objective consideration of the multitude of available clinical data, along with the visual and quantitative assessments from CCTA and SPECT, are critical for optimal patient risk stratification. We aim to provide an explainable ML approach to predict MACE using clinical, CCTA, and SPECT data. METHODS: Consecutive patients who underwent clinically indicated CCTA and SPECT myocardial imaging for suspected CAD were included and followed up for MACEs. A MACE was defined as a composite outcome that included all-cause mortality, myocardial infarction, or late revascularization. We employed an Automated Machine Learning (AutoML) approach to predict MACE using clinical, CCTA, and SPECT data. Various mainstream models with different sets of hyperparameters have been explored, and critical predictors of risk are obtained using explainable techniques on the global and patient levels. Ten-fold cross-validation was used in training and evaluating the AutoML model. RESULTS: A total of 956 patients were included (mean age 61.1 ±14.2 years, 54% men, 89% hypertension, 81% diabetes, 84% dyslipidemia). Obstructive CAD on CCTA and ischemia on SPECT were observed in 14% of patients, and 11% experienced MACE. ML prediction's sensitivity, specificity, and accuracy in predicting a MACE were 69.61%, 99.77%, and 96.54%, respectively. The top 10 global predictive features included 8 CCTA attributes (segment involvement score, number of vessels with severe plaque ≥70, ≥50% stenosis in the left marginal coronary artery, calcified plaque, ≥50% stenosis in the left circumflex coronary artery, plaque type in the left marginal coronary artery, stenosis degree in the second obtuse marginal of the left circumflex artery, and stenosis category in the marginals of the left circumflex artery) and 2 clinical features (past medical history of MI or left bundle branch block, being an ever smoker). CONCLUSION: ML can accurately predict risk of developing a MACE in patients suspected of CAD undergoing SPECT MPI and CCTA. ML feature-ranking can also show, at a sample- as well as at a patient-level, which features are key in making such a prediction.

Prognostic value of positron emission tomography derived myocardial flow reserve: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Positron Emission Tomography (PET)-derived myocardial flow reserve (MFR) has been shown to have a role in the diagnosis and prognosis of patients with coronary artery disease (CAD). We performed a systematic review and meta-analysis to summarize the body of literature and synthesize the evidence on the prognostic role of PET-derived MFR in patients with known or suspected CAD. METHODS: A comprehensive literature search of the Medline database from its inception to August 2023, in humans, in any language, was conducted for clinical studies examining the prognostic value of PET imaging in patients of any age, sex, and CAD status. Systematic screening and data extraction of the identified studies were followed by quantitative meta-analysis of PET-MFR's role in predicting adverse clinical events using random effect model. Studies were appraised using the modified Newcastle-Ottawa tool. RESULTS: A total of 21 studies assessing the prognostic role of PET derived MFR in 46,815 patients with known and/or suspected CAD were included (mean (SD) age 66 (4) years, 48% women). The mean follow-up duration was 36 months (range 10-96). Cardiovascular risk factors were prevalent (73% hypertension, 35% diabetes and 67% dyslipidemia). The definition of the composite outcome varied between studies, with various combinations of mortality, non-fatal myocardial infarction, hospitalization, and coronary revascularization. Pooled impaired MFR was significantly associated with an increased risk of adverse outcomes (RR = 2.94, 95% CI 2.42-3.56, p < 0.001). Results were similar in a subgroup of patients with suspected CAD. CONCLUSIONS: The available body of evidence shows that impaired PET-derived MFR measured using different tracers and PET systems is strongly associated with an increased risk of adverse cardiovascular events. Limitations of this review include observational nature of studies, marked heterogeneity in patient populations, inconsistency in thresholds to define abnormal MFR, and differing components for the composite outcome.

Prognostic value of global myocardial flow reserve in patients with history of coronary artery bypass grafting.

AIMS: It is not well understood whether positron emission tomography (PET)-derived myocardial flow reserve (MFR) is prognostic among patients with prior coronary artery bypass grafting (CABG). METHODS AND RESULTS: Consecutive patients with a clinical indication for PET were enrolled in the Houston Methodist DeBakey Heart and Vascular Center PET registry and followed prospectively for incident outcomes. The primary outcome was a composite of all-cause death, myocardial infarction (MI)/unplanned revascularization, and heart failure admissions. Cox proportional hazards models were used to study the association between MFR (<2 vs. ≥2) and incident events adjusting for clinical and myocardial perfusion imaging variables. The study population consisted of 836 patients with prior CABG; mean (SD) age 68 (10) years, 53% females, 79% Caucasian, 36% non-Hispanic, and 66% with MFR <2. Over a median (interquartile range [IQR]) follow-up time of 12 (4-24) months, there were 122 incident events (46 HF admissions, 28 all-cause deaths, 23 MI, 22 PCI/3 repeat CABG 90 days after imaging). In adjusted analyses, patients with impaired MFR had a higher risk of the primary outcome [hazard ratio (HR) 2.06; 95% CI 1.23-3.44]. Results were significant for admission for heart failure admissions (HR 2.92; 95% CI 1.11-7.67) but not for all-cause death (HR 2.01, 95% CI 0.85-4.79), or MI/UR (HR 1.93, 95% CI 0.92-4.05). CONCLUSION: Among patients with a history of CABG, PET-derived global MFR <2 may identify those with a high risk of subsequent cardiovascular events, especially heart failure, independent of cardiovascular risk factors and perfusion data.

The Role of Cardiac PET in Diagnosis and Prognosis of Ischemic Heart Disease: Optimal Modality Across Different Patient Populations.

PURPOSE OF REVIEW: Despite single-photon emission computerized tomography (SPECT) being the most used nuclear imaging technique for diagnosis of coronary artery disease (CAD), many now consider positron emission tomography (PET) as a superior modality. This review will focus on the advances of cardiac PET in recent years and its advantages compared to SPECT in diagnosis and prognosis of CAD. RECENT FINDINGS: PET's higher resolution and enhanced diagnostic accuracy, as well as lower radiation exposure, all help explain the rationale for its wider spread and use. PET also allows for measurement of myocardial blood flow (MBF) and myocardial flow reserve (MFR), which aids in several different clinical scenarios, such as diagnosing multivessel disease or identifying non-responders. PET has also been shown to be useful in diagnosing CAD in various specific populations, such as patients with prior COVID-19 infection, cardiac transplant, and other comorbidities.

Coronary microvascular health in symptomatic patients with prior COVID-19 infection: an updated analysis.

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 <2 (adjusted odds ratio 3.1, 95% confidence interval 2.8-4.25 P < 0.001). Results were similar in clinically meaningful subgroups. The proportion of cases with MFR <2 peaked 6-9 months from imaging with a statistically non-significant downtrend afterwards and was comparable across SARS-CoV-2 variants but increased with increasing severity of infection. 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.

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.

Incremental prognostic value of positron emission tomography-derived myocardial flow reserve in patients with and without diabetes mellitus.

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 (<2). During a median follow-up of 22.6 (7.8-42.5) months, 619 patients (10%, 3.8 per 1000 person-years) experienced the primary outcome. Impaired MFR (MFR < 2) was significantly associated with the primary outcome in patients with and without diabetes (diabetes: HR 1.8, 95% CI 1.4-2.3, P < 0.001; no diabetes: 1.4, 95% CI 1.0-2.1, P = 0.046). There was no interaction between diabetes status and MFR (P = 0.234). Results were consistent across subgroups of patients with no CAD and normal perfusion study. CONCLUSION: PET-derived MFR has a strong independent and incremental prognostic role in patients with diabetes and those without diabetes.

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.

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.

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.

Incremental prognostic value of digital positron emission tomography derived myocardial flow reserve: A prospective cohort study.

BACKGROUND: 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. METHODS: 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 occurring >90 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. RESULTS: 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). CONCLUSION: MFR derived from digital PET scanners has an independent and incremental prognostic role in patients with suspected or known CAD.