Assessment of cerebral glucose metabolism in patients with heart failure by 18F-FDG PET/CT imaging.

BACKGROUND: To evaluate the cerebral metabolism in patients with heart failure (HF). METHODS: One hundred and two HF patients were prospectively enrolled, who underwent gated 99mTc-sestamibi single photon emission computed tomography (SPECT)/CT, cardiac and cerebral 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. Fifteen healthy volunteers served as controls. Patients were stratified by extent of hibernating myocardium (HM) and left ventricular ejection fraction (LVEF) into 4 groups where Group1: HM < 10% (n = 33); Group2: HM ≥ 10%, LVEF < 25% (n = 34); Group3: HM ≥ 10%, 25% ≤ LVEF ≤ 40% (n = 16) and Group 4: LVEF > 40% (n = 19). The standardized uptake value (SUV) in the whole brain (SUVwhole-brain) and the SUV ratios (SUVR) in 24 cognition-related brain regions were determined. SUVwhole-brain and SUVRs were compared between the 4 patient groups and the healthy controls. RESULTS: SUVwhole-brain (r = 0.245, P = 0.013) and SUVRs in frontal areas, hippocampus, and para-hippocampus (r: 0.213 to 0.308, all P < 0.05) were correlated with HM. SUVwhole-brain differed between four patient groups and the healthy volunteers (P = 0.016) and SUVwhole-brain in Group 1 was lower than that in healthy volunteers (P < 0.05). SUVRs of Group 3 in frontal areas were the highest among four patient subgroups (P < 0.05). CONCLUSIONS: Cerebral metabolism in the whole brain was reduced but maintained in cognition-related frontal areas in HF patients with HM and moderately impaired global left ventricular function.

Myocardial perfusion imaging: Lessons learned and work to be done-update.

As the second term of our commitment to Journal begins, we, the editors, would like to reflect on a few topics that have relevance today. These include prognostication and paradigm shifts; Serial testing: How to handle data? Is the change in perfusion predictive of outcome and which one? Ischemia-guided therapy: fractional flow reserve vs perfusion vs myocardial blood flow; positron emission tomography (PET) imaging using Rubidium-82 vs N-13 ammonia vs F-18 Flurpiridaz; How to differentiate microvascular disease from 3-vessel disease by PET? The imaging scene outside the United States, what are the differences and similarities? Radiation exposure; Special issues with the new cameras? Is attenuation correction needed? Are there normal databases and are these specific to each camera system? And finally, hybrid imaging with single-photon emission tomography or PET combined with computed tomography angiography or coronary calcium score. We hope these topics are of interest to our readers.

Interplay Between Systemic Inflammation, Myocardial Injury, and Coronary Microvascular Dysfunction in Rheumatoid Arthritis: Results From the LiiRA Study.

BACKGROUND: Coronary microvascular dysfunction as measured by myocardial flow reserve (MFR) is associated with increased cardiovascular risk in rheumatoid arthritis (RA). The objective of this study was to determine the association between reducing inflammation with MFR and other measures of cardiovascular risk. METHODS AND RESULTS: Patients with RA with active disease about to initiate a tumor necrosis factor inhibitor were enrolled (NCT02714881). All subjects underwent a cardiac perfusion positron emission tomography scan to quantify MFR at baseline before tumor necrosis factor inhibitor initiation, and after tumor necrosis factor inhibitor initiation at 24 weeks. MFR <2.5 in the absence of obstructive coronary artery disease was defined as coronary microvascular dysfunction. Blood samples at baseline and 24 weeks were measured for inflammatory markers (eg, high-sensitivity C-reactive protein [hsCRP], interleukin-1b, and high-sensitivity cardiac troponin T [hs-cTnT]). The primary outcome was mean MFR before and after tumor necrosis factor inhibitor initiation, with Δhs-cTnT as the secondary outcome. Secondary and exploratory analyses included the correlation between ΔhsCRP and other inflammatory markers with MFR and hs-cTnT. We studied 66 subjects, 82% of which were women, mean RA duration 7.4 years. The median atherosclerotic cardiovascular disease risk was 2.5%; 47% had coronary microvascular dysfunction and 23% had detectable hs-cTnT. We observed no change in mean MFR before (2.65) and after treatment (2.64, P=0.6) or hs-cTnT. A correlation was observed between a reduction in hsCRP and interleukin-1b with a reduction in hs-cTnT. CONCLUSIONS: In this RA cohort with low prevalence of cardiovascular risk factors, nearly 50% of subjects had coronary microvascular dysfunction at baseline. A reduction in inflammation was not associated with improved MFR. However, a modest reduction in interleukin-1b and no other inflammatory pathways was correlated with a reduction in subclinical myocardial injury. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02714881.

Blood flow, flow reserve, and glucose utilization in viable and nonviable myocardium in patients with ischemic cardiomyopathy.

PURPOSE: The aim of the study was to determine whether glucose uptake in viable myocardium of ischemic cardiomyopathy patients depends on rest myocardial blood flow (MBF) and the residual myocardial flow reserve (MFR). METHODS: Thirty-six patients with ischemic cardiomyopathy (left ventricular ejection fraction 25 ± 10 %) were studied with (13)N-ammonia and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty age-matched normals served as controls. Regional MBF was determined at rest and during dipyridamole hyperemia and regional FDG extraction was estimated from regional FDG to (13)N-ammonia activity ratios. RESULTS: Rest MBF was reduced in viable (0.42 ± 0.18 ml/min per g) and nonviable regions (0.32 ± 0.09 ml/min per g) relative to remote regions (0.68 ± 0.23 ml/min per g, p < 0.001) and to normals (0.63 ± 0.13 ml/min per g). Dipyridamole raised MBFs in controls, remote, viable, and nonviable regions. MBFs at rest (p < 0.05) and stress (p < 0.05) in viable regions were significantly higher than that in nonviable regions, while MFRs did not differ significantly (p > 0.05). Compared to MFR in remote myocardium, MFRs in viable regions were similar (1.39 ± 0.56 vs 1.70 ± 0.45, p > 0.05) but were significantly lower in nonviable regions (1.23 ± 0.43, p < 0.001). Moreover, the FDG and thus glucose extraction was higher in viable than in remote (1.40 ± 0.14 vs 0.90 ± 0.20, p < 0.001) and in nonviable regions (1.13 ± 0.21, p < 0.001). The extraction of FDG in viable regions was independent of rest MBF but correlated inversely with MFRs (r =-0.424, p < 0.05). No correlation between the FDG extraction and MFR was observed in nonviable regions. CONCLUSION: As in the animal model, decreasing MFRs in viable myocardium are associated with increasing glucose extraction that likely reflects a metabolic adaptation of remodeling hibernating myocytes.

Myocardial Perfusion PET for the Detection and Reporting of Coronary Microvascular Dysfunction: A JACC: Cardiovascular Imaging Expert Panel Statement.

Angina pectoris and dyspnea in patients with normal or nonobstructive coronary vessels remains a diagnostic challenge. Invasive coronary angiography may identify up to 60% of patients with nonobstructive coronary artery disease (CAD), of whom nearly two-thirds may, in fact, have coronary microvascular dysfunction (CMD) that may account for their symptoms. Positron emission tomography (PET) determined absolute quantitative myocardial blood flow (MBF) at rest and during hyperemic vasodilation with subsequent derivation of myocardial flow reserve (MFR) affords the noninvasive detection and delineation of CMD. Individualized or intensified medical therapies with nitrates, calcium-channel blockers, statins, angiotensin-converting enzyme inhibitors, angiotensin II type 1-receptor blockers, beta-blockers, ivabradine, or ranolazine may improve symptoms, quality of life, and outcome in these patients. Standardized diagnosis and reporting criteria for ischemic symptoms caused by CMD are critical for optimized and individualized treatment decisions in such patients. In this respect, it was proposed by the cardiovascular council leadership of the Society of Nuclear Medicine and Molecular Imaging to convene thoughtful leaders from around the world to serve as an independent expert panel to develop standardized diagnosis, nomenclature and nosology, and cardiac PET reporting criteria for CMD. This consensus document aims to provide an overview of the pathophysiology and clinical evidence of CMD, its invasive and noninvasive assessment, standardization of PET-determined MBFs and MFR into "classical" (predominantly related to hyperemic MBFs) and "endogen" (predominantly related to resting MBF) normal coronary microvascular function or CMD that may be critical for diagnosis of microvascular angina, subsequent patient care, and outcome of clinical CMD trials.

The influence of insulin resistance, obesity, and diabetes mellitus on vascular tone and myocardial blood flow.

Among individuals with cardiovascular risk factors, reductions in coronary vasodilator capacity with or without diabetes mellitus (DM) carry important diagnostic and prognostic information. Positron emission tomography (PET) myocardial perfusion imaging in concert with tracer kinetic modeling allows the assessment of absolute regional myocardial blood flow (MBF) at rest and its response to various forms of vasomotor stress. Such noninvasive evaluation of myocardial flow reserve (MFR) or the vasodilator capacity of the coronary circulation expands the possibilities of conventional scintigraphic myocardial perfusion imaging from identifying flow-limiting epicardial coronary artery lesions to understanding the underlying pathophysiology of diabetic vasculopathy, microcirculatory dysfunction, and its atherothrombotic sequelae. Invaluable mechanistic insights were recently reported with PET by unraveling important effects of insulin resistance, obesity, and DM on the function of the coronary circulation. Such noninvasive assessment of coronary circulatory dysfunction enables monitoring its response to antidiabetic medication and/or behavioral interventions related to weight, diet, and physical activity that may evolve as a promising tool for an image-guided and personalized preventive diabetic vascular care. Whether PET-guided improvement or normalization of hyperemic MBF and/or MFR will translate into improved patient outcome in DM is a laudable goal to pursue next.

Incidental Detection of Elastofibroma Dorsi With 68Ga-FAPI-46 and 18F-FDG PET/CT in a Patient With Esophageal Cancer.

ABSTRACT: A 71-year-old man underwent 18F-FDG and 68Ga-FAPI-46 PET/CT for initial staging prior to surgery of a squamous cell carcinoma of the lower esophagus under the prospective study NCT04147494. Both scans showed increased uptake in the mid and distal esophagus without evidence of metastatic disease. A soft tissue right infrascapular mass with mild 18F-FDG and moderate 68Ga-FAPI-46 uptake was incidentally found. The patient underwent robotic-assisted Ivor-Lewis esophagectomy and excision of the right infrascapular mass. Histopathology of the right chest wall mass confirmed the diagnosis of elastofibroma.

Effect of hormone replacement therapy on vasomotor function of the coronary microcirculation in post-menopausal women with medically treated cardiovascular risk factors.

AIMS: The aim of this study was to evaluate the effect of hormone replacement therapy (HRT) on coronary vasomotor function in post-menopausal women (PM) with medically treated cardiovascular risk factors (RFs) in a cross-sectional and a longitudinal follow-up (FU) study. METHODS AND RESULTS: Myocardial blood flow (MBF) response to cold pressor testing (CPT) and during pharmacologically induced hyperaemia was measured with positron emission tomography in pre-menopausal women (CON), in PM with HRT and without HRT, and repeated in PM after a mean FU of 24 +/- 14 months. When compared with CON at baseline, the endothelium-related change in MBF (DeltaMBF) to CPT progressively declined in PM with HRT and without HRT (0.35 +/- 0.23 vs. 0.24 +/- 0.20 and 0.16 +/- 0.12 mL/g/min; P = 0.171 and P = 0.021). In PM without HRT and in those with HRT at baseline but with discontinuation of HRT during FU, the endothelium-related DeltaMBF to CPT was significantly less at FU than at baseline (0.05 +/- 0.19 vs. 0.16 +/- 0.12 and -0.03 +/- 0.14 vs. 0.25 +/- 0.18 mL/g/min; P = 0.023 and P = 0.001), whereas no significant change was observed in PM with HRT (0.19 +/- 0.22 vs. 0.23 +/- 0.22 mL/g/min; P = 0.453). Impaired hyperaemic MBFs when compared with CON were not significantly altered from those at baseline exam. CONCLUSION: Long-term administration of oestrogen may contribute to maintain endothelium-dependent coronary function in PM with medically treated cardiovascular RFs.

Improvement in coronary endothelial function is independently associated with a slowed progression of coronary artery calcification in type 2 diabetes mellitus.

AIMS: To examine a relationship between alterations of structure and function of the arterial wall in response to glucose-lowering therapy in type 2 diabetes mellitus (DM) after a 1-year follow-up (FU). METHODS AND RESULTS: In DM (n = 22) and in healthy controls (n = 17), coronary artery calcification (CAC) was assessed with electron beam tomography and carotid intima-media thickness (IMT) with ultrasound, whereas coronary function was determined with positron emission tomography-measured myocardial blood flow (MBF) at rest, during cold pressor testing (CPT), and during adenosine stimulation at baseline and after FU. The decrease in plasma glucose in DM after a mean FU of 14 +/- 1.9 months correlated with a lower progression of CAC and carotid IMT (r = 0.48, P < or = 0.036 and r = 0.46, P < or = 0.055) and with an improvement in endothelium-related DeltaMBF to CPT and to adenosine (r = 0.46, P < or = 0.038 and r = 0.36, P < or = 0.056). After adjusting for metabolic parameters by multivariate analysis, the increases in DeltaMBF to CPT after glucose-lowering treatment remained a statistically significant independent predictor of the progression of CAC (P < or = 0.001 by one-way analysis of variance). CONCLUSION: In DM, glucose-lowering treatment may beneficially affect structure and function of the vascular wall, whereas the observed improvement in endothelium-related coronary artery function may also mediate direct preventive effects on the progression of CAC.

Coronary microvascular resistance: methods for its quantification in humans.

Coronary microvascular dysfunction is a topic that has recently gained considerable interest in the medical community owing to the growing awareness that microvascular dysfunction occurs in a number of myocardial disease states and has important prognostic implications. With this growing awareness, comes the desire to accurately assess the functional capacity of the coronary microcirculation for diagnostic purposes as well as to monitor the effects of therapeutic interventions that are targeted at reversing the extent of coronary microvascular dysfunction. Measurements of coronary microvascular resistance play a pivotal role in achieving that goal and several invasive and noninvasive methods have been developed for its quantification. This review is intended to provide an update pertaining to the methodology of these different imaging techniques, including the discussion of their strengths and weaknesses.

Structural alterations of the coronary arterial wall are associated with myocardial flow heterogeneity in type 2 diabetes mellitus.

PURPOSE: To determine the relationship between carotid intima-media thickness (IMT), coronary artery calcification (CAC), and myocardial blood flow (MBF) at rest and during vasomotor stress in type 2 diabetes mellitus (DM). METHODS: In 68 individuals, carotid IMT was measured using high-resolution vascular ultrasound, while the presence of CAC was determined with electron beam tomography (EBT). Global and regional MBF was determined in milliliters per gram per minute with (13)N-ammonia and positron emission tomography (PET) at rest, during cold pressor testing (CPT), and during adenosine (ADO) stimulation. RESULTS: There was neither a relationship between carotid IMT and CAC (r = 0.10, p = 0.32) nor between carotid IMT and coronary circulatory function in response to CPT and during ADO (r = -0.18, p = 0.25 and r = 0.10, p = 0.54, respectively). In 33 individuals, EBT detected CAC with a mean Agatston-derived calcium score of 44 +/- 18. There was a significant difference in regional MBFs between territories with and without CAC at rest and during ADO-stimulated hyperemia (0.69 +/- 0.24 vs. 0.74 +/- 0.23 and 1.82 +/- 0.50 vs. 1.95 +/- 0.51 ml/g/min; p < or = 0.05, respectively) and also during CPT in DM but less pronounced (0.81 +/- 0.24 vs. 0.83 +/- 0.23 ml/g/min; p = ns). The increase in CAC was paralleled with a progressive regional decrease in resting as well as in CPT- and ADO-related MBFs (r = -0.36, p < or = 0.014; r = -0.46, p < or = 0.007; and r = -0.33, p < or = 0.041, respectively). CONCLUSIONS: The absence of any correlation between carotid IMT and coronary circulatory function in type 2 DM suggests different features and stages of early atherosclerosis in the peripheral and coronary circulation. PET-measured MBF heterogeneity at rest and during vasomotor stress may reflect downstream fluid dynamic effects of coronary artery disease (CAD)-related early structural alterations of the arterial wall.

Long-term survival of patients with viable and nonviable aneurysms assessed by 99mTc-MIBI SPECT and 18F-FDG PET: a comparative study of medical and surgical treatment.

UNLABELLED: The prognostic value of myocardial viability assessment on left ventricular (LV) aneurysms remains undetermined. We aimed, first, to evaluate the long-term survival benefit of assessing the viability of the aneurysmal myocardium in patients with ischemic cardiomyopathy and, second, in the revascularization subgroup, to compare the short-term effects on LV function and clinical symptoms in patients treated by revascularization alone or by revascularization plus aneurysmectomy. METHODS: Seventy consecutive patients with an LV aneurysm who underwent 99mTc-sestamibi SPECT and 18F-FDG PET were followed up for a median of 6.8 y (range, 0.1-8.8 y). Only cardiac death during follow-up served as the endpoint. Patients were classified into 4 groups by aneurysmal viability and by treatment strategy (medical or surgical). Further, the effects of aneurysmectomy on LV function at 3 mo were evaluated by an analysis of revascularized patients grouped by aneurysmal viability and by aneurysmectomy. RESULTS: Twenty-four patients were assigned to medical therapy, and 46 patients were assigned to surgery (18 revascularization alone and 28 revascularization plus aneurysmectomy). The annual cardiac mortality rate in patients with a viable aneurysm treated medically (n = 10) was significantly higher than that in patients with a viable aneurysm treated surgically (n = 23) (11.6% vs. 1.5%, chi2 = 12.87, P < 0.0001) and was also significant higher than that in patients with a nonviable aneurysm treated medically (n = 14) (chi2 = 4.13, P < 0.05) or surgically (n = 23) (chi2 = 10.46, P = 0.001). Multivariate analysis showed that the aneurysmal mismatch score (P = 0.003) and surgical therapy (P = 0.001) were independent predictors of cardiac death. Improvement of LV function and symptoms after revascularization (P < 0.05) was observed in patients with revascularization plus aneurysmectomy and in patients with a viable aneurysm and revascularization only. CONCLUSION: Viability in LV aneurysm in patients with ischemic cardiomyopathy was a negative independent predictor of survival. Compared with medical therapy, coronary revascularization was associated with improved long-term survival, symptoms, and LV function in patients with a viable aneurysm. These findings warrant further prospective investigations.

[Impact of viable myocardium assessed by 99Tcm-MIBI SPECT and 18F-FDG PET imaging on clinical outcome of patients with left ventricular aneurysm underwent revascularization].

OBJECTIVE: To evaluate the impact of viable myocardium assessed by (99)Tc()m-MIBI SPECT and (18)F-fluorodeoxyglucose (FDG) PET imaging in patients with left ventricular aneurysm (LVA) underwent revascularization (RVS). METHODS: Forty-six consecutive patients with LVA (mean LVEF 36% +/- 7%), underwent (99)Tc(m)-sestamibi SPECT and (18)F-FDG PET examinations and received RVS therapy, were followed-up for a mean period of 80 +/- 27 months. Viable myocardium in aneurysm was defined as perfusion-metabolism mismatch score (MMS) >/= 2.0. Patients were divided into four groups by aneurysm viability and aneurysmectomy. Group A1 (n = 8): viability-; Group A2 (n = 15): viability-, aneurysmectomy; Group B1 (n = 10): viability +; and Group B2 (n = 13): viability +, aneurysmectomy. RESULTS: The cardiac event rates during follow up were similar among groups [A1 (25%, 2/8), B1 (40%, 6/15), A2 (20%, 2/10) and B2 (31%, 4/13; P > 0.05)]. After revascularization, LVEF was improved (> 10%) in groups A2, B1 and B2 (P < 0.05). Multivariate logistic regression analysis showed that LV-MMS (OR = 2.34, 95% CI 1.08 - 5.06, P < 0.05), distal vessel disease (OR = 0.008, 95% CI 0.001 - 0.560, P < 0.05) and nonaneurysm perfusion score (OR = 0.24, 95% CI 0.07 - 0.85, P < 0.05) were significantly associated with the improvement of LVEF after revascularization. CONCLUSIONS: Long term cardiac events rate post revascularization was not affected by viable myocardium or aneurysmectomy in LVA patients. Viable myocardium in LVA patients was associated with better LVEF improvement after revascularization.