Comparison of the Prognostic Value of Global and Regional Myocardial Flow Capacity Radius, Myocardial Flow Reserve, and Stress Myocardial Blood Flow Using Rubidium-82 with SiPM PET/CT

Purpose The aim of this study was to assess the most reliable quantitative variable on Rubidium-82 (82Rb) cardiac PET/CT for predicting major adverse cardiovascular events (MACE), on the latest PET camera using silicon photomultipliers digital readout (SiPM) technology. Methods We prospectively enrolled 274 consecutive participants with suspected myocardial ischemia. Participants underwent 82Rb cardiac SiPM PET/CT and were followed-up for MACE over 652 days (interquartile range: 559 to 751 days). For each participant, global and regional myocardial flow reserve (MFR), stress myocardial blood flow (stress MBF) and their combination as myocardial flow capacity radius (MFC radius) were measured. Results On receiver operator curve analysis, MACE prediction was similar for global and regional MFR, stress MBF, and MFC radius (area under the curve; (i) Global: 0.70 vs. 0.71 and 0.73, and (ii) Regional: 0.71 vs. 0.71 and 0.73, respectively, p > 0.1 for all pairwise comparisons). On multivariable analysis, (i) Global: MFR < 1.98, stress MBF < 1.94 mL/g/min, and MFC radius < 3.12, as well as (ii) Regional: MFR < 1.75, stress MBF < 1.75 mL/g/min, and MFC radius < 2.7, emerged all as similar independent predictors of MACE (p < 0.001 for all). Conclusions Using the latest SiPM PET technology with 82Rb, global and regional MFR, stress MBF, and MFC radius are similar powerful predictors of cardiovascular event.

Capabilities of Modern Semiconductor Gamma Cameras in Radionuclide Diagnosis of Coronary Artery Disease

This paper presents a review of the literature concerning the clinical application of modern semiconductor (CZT) gamma cameras in the radioinuclide diagnosis of coronary artery disease. It contains information on the diagnostic efficacy of myocardial perfusion studies performed with those cameras compared with the widely used scintillation (Anger) cameras, an overview of their effectiveness in comparison with coronary angiography (also fractional flow reserve) and currently available clinical results of a myocardial flow reserve measured with a dynamic SPECT study. Introduction of this imaging modality to the measurement of a myocardial flow reserve aims to facilitate access to this type of study compared to the less available and more expensive PET method used so far.

Comorbidities associated with reduced myocardial flow reserve in non-obstructive disease

Introduction Microvascular Dysfunction defined as a Myocardial Flow Reserve (MFR) &lt;2 or &lt;2.5 depending on the center, may present in the absence of significant obstruction (1,2); it is included as a diagnosis criteria of Microvascular Angina (MVA) (3,4) and is an independent risk factor associated with poor prognosis (5–7). Traditional Coronary Artery Disease (CAD)risk factors have also been associated with MVA (8–10), however, there is reduced data in latin populations with high prevalence of comorbidities. The aim of this study was to identify the comorbidities that alter MFR with 13N-ammonia Positron Emission Tomography/Cardiac Tomography (PET/CT) and Cardiac Computed Tomography Angiography (CCTA) in a cardiovascular imaging referral center. Methods Retrospective cross-sectional study of patients with suspected CAD in which both PET/CT and CCTA were performed. Inclusion:CCTA with obstruction &lt;50%. Exclusion: incomplete study, previous infarction or intervention. Clinical data was assessed. Mean (±DE) or median (interquartile range) to present continuous variables according to their distribution; T student or U Man Whitney to compare them. For each variable two groups were conformed depending on its presence or absence in order to compare MFR between them. Statistical analysis was performed with Statistical Package for Social Science (SPSs Inc, Chicago, IL; version 23.0) and GraphPad Prism version 9.0. p&lt;0.05 was considered as significant. Results 335 patients included. MFR difference for each variable: female sex, hypertension (HT), Type 2 diabetes (T2D) and smoking – Appendix 1. Significant MFR difference for HT (p=0.024) and T2D (p=0.046). Severe ischemia had significant MFR reduction (p=0.006); patients with both HT and mild ischemia (p=0.018) – Appendix 2. Discussion Individuals with HT and T2D had a significantly lower MFR, consistent with previous studies (8,9). Absence of correlation with other risk factors, such as smoking (10) and female sex (11); latter may be caused by a significant lower number of women (108 vs 227). Further analysis in this subgroup ought to be done. When comparing MFR between level-of-ischemia groups, microvascular function was not reduced until severe ischemia. Remarkably, if we analyze the coexistence of HT with ischemia, MFR is reduced even in patients with mild ischemia. This finding highlights the importance of HT which alters function in early stages even in the absence of significant obstruction. This is one of the first studies correlating MFR with comorbidities in our population. Limitations the retrospective nature of the study. Conclusions MFR non-invasive assessment by PET/CT allows identifying very early stages of MVD, even in asymptomatic patients and when there's no evidence of ischemia or CAD. Therefore, timely recognition of this problem is mandatory to implement action strategies to stop the triggered events' cascade. FUNDunding Acknowledgement Type of funding sources: None.

Coronary flow quantification estimated by dynamic 320-detector CT angiography: validation by 13N ammonia PET myocardial flow reserve

Objectives: Resting coronary flow index (rCFI) estimated by 320-detector low-dose dynamic coronary CT angiography (CCTA) is a direct flow quantification using intracoronary attenuation. We propose modified-rCFI from new protocol combining dynamic scan and standard CCTA using dose-modulation, and validate its consistency with quantitative values and ischemia depicted by 13N-ammonia PET (NH3-PET). Methods: 46 patients who underwent dynamic CCTA and NH3-PET for coronary artery disease were evaluated using original rCFI in 21 patients and modified-rCFI in 25 patients. Two types of rCFI were calculated for three major coronary arteries. Myocardial blood flow (MBF) at rest and stress, myocardial flow reserve (MFR), and the presence or absence of ischemia for three major territories were depicted by NH3-PET. Coronary territories were categorized as territories with MFR <2.0, ≥2.0, or with and without ischemia. Receiver operating characteristic analysis was performed to determine the optimal cut-off of rCFI to distinguish territories with MFR <2.0 or the presence of ischemia. Results: rCFI and modified-rCFI had significant positive correlations with stress MBF and MFR. The optical cut-offs of rCFI and modified-rCFI of 0.39 and 0.61 could detect territories with MFR <2.0, with AUCs of 0.75 and 0.73, sensitivities of 48 and 34%, and specificities of 97 and 98%. Optimal cut-offs of rCFI and modified-rCFI distinguished ischemic segments from non-ischemic segments, with AUCs of 0.75 and 0.91, sensitivities of 53 and 50%, and specificities of 93 and 95%. Conclusion: Two types of rCFI correlated with quantitative values from NH3-PET, and were consistent with a high specificity in detecting functional ischemia. Advances in knowledge: rCFI can contribute as additional functional test over standard CCTA in clinical work-up.

Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus: The SIMPLE Trial

Background Sodium–glucose cotransporter 2 inhibitors reduce hospitalizations for heart failure and cardiovascular death, although the underlying mechanisms have not been resolved. The SIMPLE trial (The Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus) investigated the effects of empagliflozin on myocardial flow reserve (MFR) reflecting microvascular perfusion, in patients with type 2 diabetes mellitus at high cardiovascular disease risk. Methods and Results We randomized 90 patients to either empagliflozin 25 mg once daily or placebo for 13 weeks, as add‐on to standard therapy. The primary outcome was change in MFR at week 13, quantified by Rubidium‐82 positron emission tomography/computed tomography. The secondary key outcomes were changes in resting rate‐pressure product adjusted MFR, changes to myocardial flow during rest and stress, and reversible cardiac ischemia. Mean baseline MFR was 2.21 (95% CI, 2.08–2.35). There was no change from baseline in MFR at week 13 in either the empagliflozin: 0.01 (95% CI, −0.18 to 0.21) or placebo groups: 0.06 (95% CI, −0.15 to 0.27), with no treatment effect −0.05 (95% CI, −0.33 to 0.23). No effects on the secondary outcome parameters by Rubidium‐82 positron emission tomography/computed tomography was observed. Treatment with empagliflozin reduced hemoglobin A 1c by 0.76% (95% CI, 1.0–0.5; P <0.001) and increased hematocrit by 1.69% (95% CI, 0.7–2.6; P <0.001). Conclusions Empagliflozin did not improve MFR among patients with type 2 diabetes mellitus and high cardiovascular disease risk. The present study does not support that short‐term improvement in MFR explains the reduction in cardiovascular events observed in the outcome trials. Registration URL: https://clinicaltrialsregister.eu/ ; Unique identifier: 2016‐003743‐10.