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.

Stress myocardial blood flow reduced after severe COVID-19, not related to symptoms

Introduction Persistent cardiopulmonary symptoms after COVID-19 are reported in a large number of patients and the underlying pathology is still poorly understood. (1) Histopathologic studies revealed myocardial macrophage infiltrates in deceased patients, likely an unspecific finding of severe illness, and increased prevalence of micro- and macrovascular thrombi. (2) We examined whether microvascular perfusion, measured by quantitative cardiac magnetic resonance under vasodilator stress, was altered post COVID-19. Methods Our population consisted of 12 patients from the Pa-COVID-19-Study of the Charité Berlin, which received a cardiac MRI as part of a systematic follow up post discharge, 10 patients that presented at the German Heart Center Berlin with persistent cardiac symptoms post COVID-19 and 12 patients from the Kings College London referred for stress MRI and previous COVID-19. The scan protocol included standard functional, edema and scar imaging and quantitative stress and rest perfusion to assess both macro- and microvascular coronary artery disease. The pharmacological stress agent was regadenosone in 20 and adenosine in 13 of the patients. To control for the higher heart rate increase under regadenosone compared to adenosine, we calculated the myocardial blood flow per heartbeat (MBF_HRi) under stress. Results The median time between first positive PCR for COVID-19 and the CMR exam was 2 months (Range 0 to 12). None of the 33 patients exhibited signs of myocardial edema. One patient with a previous history of myocarditis had focal fibrosis. Three patients with known coronary artery disease showed ischemic Late Enhancement. Five patients had a small pericardial effusion; one of these four patients showed slight focal pericardial edema and LGE, consistent with mild focal pericarditis. Five Patients had a stress-induced focal perfusion deficit. Mean Stress MBF_HRi was 32.5±6.5 μl/beat/g. Stress MBF_HRi was negatively correlated with COVID-19 severity (rho=−0.361, P=0.039) and age (r=−0.452, P=0.009). The correlation with COVID-19 severity remained significant after controlling for age (rho=−0.390, P=0.027). There was no apparent difference in stress MBF_HRi between patients with and without persistent chest pain (34.5 vs. 31.5 μl/beat/g, P=0.229) Conclusion While vasodilator-stress myocardial blood flow after COVID-19 was negatively correlated to COVID-19 severity, it was not correlated to the presence of chest pain. The etiology of persistent cardiac symptoms after COVID-19 remains unclear. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Philips Figure 1. A) Quantitative regadenosone stress myocardial blood flow (MBF) map, medial short axis slice, in a patient with persistent cardiac symptoms after COVID-19. B) Boxplot of stress MBF per heart beat by COVID-19 severity, showing decreasing MBF with increasing COVID-19 severity.

Global and segmental absolute stress myocardial blood flow in prediction of cardiac events: [15O] water positron emission tomography study

Purpose We evaluated the value of reduced global and segmental absolute stress myocardial blood flow (sMBF) quantified by [15O] water positron emission tomography (PET) for predicting cardiac events in patients with suspected obstructive coronary artery disease (CAD). Methods Global and segmental sMBF during adenosine stress were retrospectively quantified in 530 symptomatic patients who underwent [15O] water PET for evaluation of coronary stenosis detected by coronary computed tomography angiography. Results Cardiovascular death, myocardial infarction, or unstable angina occurred in 28 (5.3%) patients at a 4-year follow-up. Reduced global sMBF was associated with events (area under the receiver operating characteristic curve 0.622, 95% confidence interval (95% CI) 0.538–0.707, p = 0.006). Reduced global sMBF (< 2.2 ml/g/min) was found in 22.8%, preserved global sMBF despite segmentally reduced sMBF in 35.3%, and normal sMBF in 41.9% of patients. Compared with normal sMBF, reduced global sMBF was associated with the highest risk of events (adjusted hazard ratio (HR) 6.970, 95% CI 2.271–21.396, p = 0.001), whereas segmentally reduced sMBF combined with preserved global MBF predicted an intermediate risk (adjusted HR 3.251, 95% CI 1.030–10.257, p = 0.044). The addition of global or segmental reduction of sMBF to clinical risk factors improved risk prediction (net reclassification index 0.498, 95% CI 0.118–0.879, p = 0.010, and 0.583, 95% CI 0.203–0.963, p = 0.002, respectively). Conclusion In symptomatic patients evaluated for suspected obstructive CAD, reduced global sMBF by [15O] water PET identifies those at the highest risk of adverse cardiac events, whereas segmental reduction of sMBF with preserved global sMBF is associated with an intermediate event risk.

Added Value of Transluminal Attenuation Gradient to Qualitative CCTA Ischemia Detection as Determined by 13N-ammonia PET Quantitative Myocardial Perfusion

Transluminal attenuation gradient (TAG) represents the slope of intraluminal contrast that decreases along a coronary vessel during coronary computed tomography angiography (CCTA). The aim of this study was to determine the added value of TAG to qualitative CCTA assessment of significant stenosis (>50%) detecting ischemia as determined by stress myocardial blood flow (MBF) or myocardial flow reserve (MFR) measured by positron emission tomography (PET). Individual contributions of TAG, qualitative assessment and the impact of calcium score were also investigated. Methods: We studied 38 consecutive patients that were referred due to suspected or known coronary artery disease (CAD). All patients underwent a two-phase hybrid 13N-ammonia PET/CT and CCTA. Results: TAG and presence of qualitatively assessed significant stenosis, but not calcium score, were associated with stress myocardial blood flow (MBF) and myocardial flow reserve (MFR). The area under the curves (AUC) of the linear predictor model including qualitative assessment and TAG was superior to the AUC of separate qualitative assessment or TAG for the detection of ischemia according to stress MBF (AUCs were: 88% vs. 79% and 77%; p = 0.01 and p = 0.01, respectively). Conclusions: TAG combined with qualitative CCTA assessment improved ischemia detection.

Discordance between invasive coronary flow reserve (CFR) and non-invasive myocardial flow reserve (MFR) in diffuse coronary ectasia (DCE)

Clinical use with evidence base for diagnostic and prognostic value of quantitative positron emission tomography(PET) myocardial perfusion imaging (MPI) in patients with known or suspected coronary artery disease has exponentially increased over the last decade. This case illustrates the very first time that stress myocardial blood flow(MBF) in absolute terms (ml/min/gram) and myocardial flow reserve(MFR) are augmented in three vessel diffuse coronary ectasia by N13-Ammonia PET MPI. Moreover, relative qualitative MPI demonstrated moderate-sized ischemia in right coronary artery territory with chronic total occlusion in middle segment; despite regional myocardial flow reserve remains above ischemic thresholds while regional stress myocardial blood flow is mildly reduced.