Myocardial Uptake Research Articles

The role of myocardial blood volume in the pathophysiology of angina with non-obstructed coronary arteries: The MICORDIS study

BackgroundAngina with Non-Obstructed Coronary Arteries (ANOCA) involves abnormal vasomotor responses. While reduced coronary flow is an established contributor to myocardial hypoxia, myocardial blood volume (MBV) independently regulates myocardial oxygen uptake but its role in ANOCA remains unclear. ObjectivesWe hypothesized that reduced MBV contributes to ANOCA, and associates with insulin resistance in ANOCA. MethodsMBV in ANOCA patients was compared to age- and sex-matched healthy controls. ANOCA patients underwent coronary angiography with invasive coronary function testing (CFT) to identify vasospasm and coronary microvascular dysfunction. In all subjects MBV was quantified at baseline, during hyperinsulinemia and during dobutamine-induced stress using myocardial contrast echocardiography (MCE). The hyperinsulinemic-euglycemic clamp was used to assess insulin resistance. ResultsTwenty-eight ANOCA patients (21% men, 56.8 ± 8.6 years) and 28 healthy controls (21% men, 56.5 ± 7.0 years) were included. During CFT 11% of patients showed epicardial vasospasm, 39% microvascular vasospasm, 25% coronary microvascular dysfunction, and 11% of patients had a negative CFT. ANOCA patients had significant lower insulin-sensitivity (p < 0.01). During MCE, ANOCA patients showed a significantly lower MBV at baseline (0.388 vs 0.438 mL/mL, p = 0.04), during hyperinsulinemia (0.395 vs 0.447 mL/mL, p = 0.02), and during dobutamine-induced stress (0.401 vs 0.476 mL/mL, p = 0.030). ConclusionsIn ANOCA patients MBV is diminished at baseline, during hyperinsulinemia and dobutamine-induced stress in the absence of differences in microvascular recruitment. These findings support the presence of capillary rarefaction in ANOCA patients. ANOCA patients showed metabolic insulin resistance, but insulin did not acutely alter myocardial perfusion.

Evaluation of Clinical Variables Affecting Myocardial Glucose Uptake in Cardiac FDG PET.

Cardiac 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography (FDG PET) is widely used to assess myocardial viability in patients with ischemic heart disease. While sufficient glucose uptake is a prerequisite for accurate interpretation of cardiac viability, there are a lack of data on which clinical variables have the most significant impact on myocardial glucose metabolism. Therefore, this study was designed to evaluate several clinical variables that could affect myocardial glucose metabolism. A total of 214 consecutive cases were retrospectively enrolled in this study. All subjects received 250 mg of acipimox and underwent glucose loading as preparation for cardiac FDG PET/CT. Three-dimensional regions of interest (ROIs) were drawn on PET/CT fusion images. Myocardial glucose uptake ratio (MGUR = SUVmax of LV myocardium/SUVmean of liver) was then calculated. Multiple clinical variables including body mass index (BMI), blood glucose levels at different times, administered insulin dosage, lipid profiles, and ejection fraction were measured and analyzed for correlation with myocardial glucose uptake. After dichotomizing the subjects based on a BMI of 25, each group's MGUR was compared. Myocardial uptake showed significant correlations with BMI (r = -0.162, p = 0.018), HbA1c (r = -0.150, p = 0.030), and triglyceride levels (r = -0.137, p = 0.046). No other clinical variables showed a significant correlation with myocardial glucose uptake. After multiple linear regression analysis, BMI (p = 0.032) and HbA1c (p = 0.050) showed a correlation with MGUR. In group analysis, after dividing patients based on BMI, the obese group showed significantly lower myocardial uptake than the non-obese group (3.8 ± 1.9 vs. 4.4 ± 2.1, p = 0.031). Among several clinical variables, BMI and HbA1c levels were related to myocardial glucose uptake. A prospective study would be needed to examine whether a protocol that additionally considers BMI and HbA1c levels is necessary for the current cardiac FDG PET protocol.

Factors Associated with Myocardial Uptake on Oncologic Somatostatin PET Investigations and Differentiation from Myocardial Uptake of Acute Myocarditis.

Myocardial somatostatin PET uptake is observed not only in most patients with acute myocarditis (AM) but also in some oncology patients referred for routine somatostatin PET. This raises concerns about the specificity of somatostatin PET for detecting myocarditis. The current study aims to identify factors associated with the detection of myocardial uptake on somatostatin PET scans recorded for oncology indications and differential PET criteria that characterize myocardial uptake in AM patients. Methods: We analyzed factors associated with the detection of myocardial [68Ga]Ga-DOTATOC uptake in 508 [68Ga]Ga-DOTATOC PET scans from 178 patients, performed for confirmed or suspected oncologic disease (Onc-PET) and PET criteria that could differentiate myocardial [68Ga]Ga-DOTATOC uptake in 31 patients with MRI-ascertained AM (AM-PET) from that in the Onc-PET group. Results: Significant myocardial uptake was detected in 137 (26.9%) Onc-PET scans and was independently associated with somatostatin analog treatment (exp(β), 0.805; 95% CI, 0.728-0.890; P < 0.001) and age (exp(β), 1.005; 95% CI, 1.001-1.009; P = 0.012). A comparable model was selected for predicting the myocardial-to-blood SUVmax ratio using somatostatin analog treatment (P < 0.001) and history of coronary artery disease (P = 0.022). Myocardial uptake was detected in 12.9% (25/193) of Onc-PET scans from patients treated with somatostatin analogs but in 43.4% (59/136) of untreated patients over the median age of 64 y. Myocardial uptake was apparent in all 31 AM-PET scans, with volume and intensity of uptake dramatically higher than in the 137 Onc-PET scans showing myocardial uptake. A myocardial-to-blood SUVmax ratio threshold of 2.20 provided a sensitivity of 87% (27/31) and a specificity of 88% (44/50) for differentiating myocardial uptake between the AM-PET group and an Onc-PET group restricted to patients with clinical characteristics comparable to those of patients in the AM-PET group (≤64 y of age, no coronary artery disease history, and no somatostatin agonists). A myocardial uptake volume threshold of 18 cm3 provided comparable diagnostic accuracy (sensitivity, 84% [26/31]; specificity, 94% [47/50]). Conclusion: Myocardial uptake was detected in 26.9% of somatostatin PET scans recorded for oncology indications. This rate was decreased by somatostatin analog treatments and increased in older individuals. However, somatostatin PET scans, analyzed with the quantitative criterion of uptake intensity or volume, are able to identify AM and to differentiate it from myocardial uptake of other origins.

Quantitative 99mTc-pyrophosphate myocardial uptake: Changes on transthyretin stabilization therapy

BackgroundQuantitative technetium-99m-pyrophosphate cardiac single-photon emission computed tomography (99mTc-PYP SPECT/CT) is an emerging method for estimating myocardial burden of transthyretin cardiac amyloidosis (ATTR-CA), but its efficacy in monitoring longitudinal changes remains uncertain. We aimed to investigate longitudinal changes in cardiac ATTR amyloid burden following transthyretin stabilization therapy using visual and quantitative 99mTc-PYP SPECT/CT and to relate these with changes in cardiac biomarkers and function. MethodsThis prospective longitudinal cohort study investigated changes in 99mTc-PYP SPECT/CT in 23 participants with ATTR-CA on transthyretin stabilization therapy (median: 2.6 years). Quantitative analysis included left ventricular (LV) standardized uptake values (SUVs) (SUVmax, SUVmean), cardiac amyloid activity (CAA; SUVmean∗LV activity volume), and percent injected dose (%ID) (mean activity concentration∗LV activity volume/injected activity), calculated using a threshold of >1.5 times left atrial blood pool activity concentration on SPECT/CT. Longitudinal changes of paired continuous and ordinal variables were analyzed using Wilcoxon signed-rank test. ResultsFollowing therapy, visual grade decreased significantly (P = 0.003). Several quantitative 99mTc-PYP metrics also decreased significantly: SUVmax (median −0.75, P = 0.011), CAA (median: −406.6, P < 0.001), and %ID (median: −0.45, P < 0.001). Serum transthyretin levels improved (median: +6.5 mg/dL, P = 0.008). Echocardiographic parameters (global longitudinal strain, LV mass index, and LV wall thickness), N-terminal pro-B-type natriuretic peptide, and estimated glomerular filtration rate remained stable. ConclusionsFavorable changes in 99mTc-PYP myocardial uptake were observed in participants on transthyretin stabilization therapy, whereas echocardiographic parameters and biomarkers remained stable. These results likely signify myocardial ATTR amyloid stabilization rather than amyloid burden regression. Further investigation is needed to understand the implications of these findings.

Relationship Between Myocardial FDG Uptake, Gender, and Clinical Comorbidities in Oncological Patients Undergoing PET/CT Examinations

Relationship Between Myocardial FDG Uptake, Gender, and Clinical Comorbidities in Oncological Patients Undergoing PET/CT Examinations

Relationship of Ketosis With Myocardial Glucose Uptake Among Patients Undergoing FDG PET/CT for Evaluation of Cardiac Sarcoidosis.

Fluorine-18 fluorodeoxyglucose (FDG) with positron emission tomography (PET) is the standard for detecting myocardial inflammation in cardiac sarcoidosis, requiring preparation with the ketogenic diet (KD) to achieve myocardial glucose suppression. Despite this, incomplete myocardial glucose suppression remains a significant issue, and strategies to reduce myocardial glucose uptake (MGU) and identify incomplete myocardial glucose suppression are required. This study sought to understand the relationship between point-of-care beta-hydroxybutyrate (BHB) and different patterns of MGU and between KD and fasting duration with MGU in patients undergoing evaluation for cardiac sarcoidosis. We prospectively included 471 outpatients who underwent FDG-PET for cardiac sarcoidosis evaluation, followed the KD for 1 (n=100), 2 (n=29), and ≥3 days (n=342), fasted for at least 12 hours, and had BHB levels measured immediately before FDG injection. Images were classified as (1) no MGU (negative), (2) focal/multifocal (positive), (3) diffuse (nondiagnostic), or (4) nonspecific uptake (NS-MGU). Cardiac FDG-PET scans were interpreted as the following: 376 (79.83%) negative; 61 (12.95%) positive; 14 (2.97%) diffuse; and 20 (4.25%) NS-MGU. There was a strong negative relationship between BHB levels and MGU (P<0.0001). BHB levels increased significantly with KD duration (P<0.0001) and fasting time (P=0.0067). The combined rate of diffuse, NS-MGU, and positive scans (34%, 28%, 16%) decreased inversely with KD duration (1, 2, and ≥3 days, respectively). However, MGU was not different across different fasting times (P=0.6). Blood glucose levels were not associated with MGU (P=0.17) and only weakly associated with BHB levels (R2=0.03; P<0.001). We observed a strong inverse relationship between ketosis and patterns of MGU. Longer KD and fasting durations are associated with higher ketosis. However, only KD duration was associated with lower rates of MGU. Measurement of BHB levels before FDG-PET using point-of-care testing is feasible and may facilitate the management of patients referred for myocardial inflammation.

Myocardial work by pressure-strain loop is associated with molecular imaging of fibroblast activation in hypertensive hearts using 99mTc-HFAPI SPECT.

99mTc-HFAPI can visualize fibroblast activation in hypertensive hearts. Myocardial work (MW) reflects the cardiac mechanical properties after accounting for the afterload in hypertensive patients. We investigated whether MW was associated with increased uptake of 99mTc-HFAPI. A total of 97 hypertensive patients and 41 healthy volunteers were prospectively recruited. Global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) were analyzed. According to whether myocardial uptake of FAPI was higher than the adjacent blood pool, hypertensive patients were divided into two groups, namely: FAPI + and FAPI- group, respectively. GWI, GCW and GWE of the FAPI + group were lower than the FAPI- group. The value of GWW in the FAPI + group was higher than in the FAPI- group. Multiple regression analyses revealed GWI, GWW and GWE were independently associated with early myocardial fibrosis. According to receiver operating characteristics (ROC) analysis, the best cutoff points for FAPI + of GWI, GWW and GWE were 1968.50 mmHg% (AUC: 0.687, 95% CI: 0.581-0.793, P = 0.002), 133.00 mmHg% (AUC: 0.778, 95% CI: 0.688-0.869, P < 0.001) and 95.07% (AUC: 0.813, 95% CI: 0.730-0.896, P < 0.001), respectively. GWI, GWW and GWE were impaired in hypertensive patients with cardiac 99mTc-HFAPI uptake and were associated with fibroblast activation in hypertensive hearts.

Role of Textural Analysis Parameters Derived from FDG PET/CT in Diagnosing Cardiac Sarcoidosis

Abstract Introduction Texture and radiomic analysis characterize the lesion's phenotype and evaluate its microenvironment in quantitative terms. The aim of this study was to investigate the role of textural features of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography–computed tomography (PET/CT) images in differentiating patients with cardiac sarcoidosis (CS) from patients with physiologic myocardial uptake. Methods This is a retrospective, single-center study of 67 patients, 17 diagnosed CS patients, and 50 non-CS patients. These patients underwent FDG PET/CT for the diagnosis of CS. The non-CS group underwent 18F-FDG PET/CT for other oncological indications. The PET/CT images were then processed in a commercially available textural analysis software. Region of interest was drawn over primary tumor with a 40% threshold and was processed further to derive 92 textural and radiomic parameters. These parameters were then compared between the CS group and the non-CS group. Receiver operating characteristics (ROC) curves were used to identify cutoff values for textural features with a p-value &lt; 0.05 for statistical significance. These parameters were then passed through a principle component analysis algorithm. Five different machine learning classifiers were then tested on the derived parameters. Results A retrospective study of 67 patients, 17 diagnosed CS patients, and 50 non-CS patients, was done. Twelve textural analysis parameters were significant in differentiating between the CS group and the non-CS group. Cutoff values were calculated for these parameters according to the ROC curves. The parameters were Discretized_HISTO_Entropy, GLCM_Homogeneity, GLCM_Energy, GLRLM_LRE, GLRLM_LGRE, GLRLM_SRLGE, GLRLM_LRLGE, NGLDM_Coarseness, GLZLM_LZE, GLZLM_LGZE, GLZLM_SZLGE, and GLZLM_LZLGE. The gradient boosting classifier gave best results on these parameters with 85.71% accuracy and an F1 score of 0.86 (max 1.0) on both classes, indicating the classifier is performing well on both classes. Conclusion Textural analysis parameters could successfully differentiate between the CS and non-CS groups noninvasively. Larger multicenter studies are needed for better clinical prognostication of these parameters.

Construction and Preliminary Evaluation of Two 18F-Labeled Radiopharmaceuticals for Myocardial Perfusion Imaging.

PET myocardial perfusion imaging (MPI) is the gold standard for the noninvasive diagnosis of ischemic myocardial. Construction of 18F-labeled PET MPI probe showed benefits to reduce the imaging cost, and enhance the image quality and patient-friendliness. Two 18F-labeled MPI probes (18F-BoMPI) were developed. Detailed in vitro/vivo evaluation including photophysical properties, in vitro stability, myocardial cell uptake kinetics and mechanisms, cytotoxicity and IC50, biodistribution and plasma clearance curve were investigated. Resting and stressing myocardial perfusion PET imaging were performed in healthy and myocardial ischemic mice. 18F-BoMPI could be quickly labeled and easily postprocessed, and demonstrated excellent in vitro stability. Cell assays indicated that 18F-BoMPI exhibited mitochondria-targeting but potential-independent myocardial uptake. In vivo evaluation revealed the effective myocardial uptake and rapid background clearance. PET MPI confirmed effective probe accumulation in the healthy heart, but rapidly clearance in the background, making heart clearly delineated in the images. Ischemic myocardial could be clearly distinguished as the region of radioactivity sparsity in PET MPI. The 18F-labeled probes showed great potentials to reduce the practicability threshold of PET MPI.

Preclinical evaluation of [18F]SYN1 and [18F]SYN2, novel radiotracers for PET myocardial perfusion imaging

BackgroundPositron emission tomography (PET) is now an established diagnostic method for myocardial perfusion imaging (MPI) in coronary artery disease, which is the main cause of death globally. The available tracers show several limitations, therefore, the 18F-labelled tracer is in high demand nowadays. The preclinical studies on normal Wistar rats aimed to characterise two potential, novel radiotracers, [18F]SYN1 and [18F]SYN2, to evaluate which is a better candidate for PET MPI cardiotracer.ResultsThe dynamic microPET images showed rapid myocardial uptake for both tracers. However, the uptake was higher and also stable for [18F]SYN2, with an average standardized uptake value of 3.8. The biodistribution studies confirmed that [18F]SYN2 uptake in the cardiac muscle was high and stable (3.02%ID/g at 15 min and 2.79%ID/g at 6 h) compared to [18F]SYN1 (1.84%ID/g at 15 min and 0.32%ID/g at 6 h). The critical organs determined in dosimetry studies were the small intestine and the kidneys. The estimated effective dose for humans was 0.00714 mSv/MBq for [18F]SYN1 and 0.0109 mSv/MBq for [18F]SYN2. The tested dose level of 2 mg/kg was considered to be the No Observed Adverse Effect Level (NOAEL) for both candidates. The better results were achieved for [18F]SYN2, therefore, further preclinical studies were conducted only for this tracer. Radioligand binding assays showed significant responses in 3 from 68 assays: muscarinic acetylcholine M1 and M2 receptors and potassium channel hERG. The compound was mostly metabolised via an oxidative N-dealkylation, while the fluor substituent was not separated from the molecule.Conclusion[18F]SYN2 showed a favourable pharmacodynamic and pharmacokinetic profile, which enabled a clear visualization of the heart in microPET. The compound was well-tolerated in studies in normal rats with moderate radiation exposure. The results encourage further exploration of [18F]SYN2 in clinical studies.

Impaired balance between coronary blood flow and myocardial metabolism in postpartum swine

Understanding of the mechanisms contributing to the increased maternal susceptibility for major adverse cardiovascular events in the postpartum period remains poor. Accordingly, this study tested the hypothesis that the balance between coronary blood flow and myocardial metabolism is compromised during the puerperium period (35–45 days post-delivery) in swine. Systemic and coronary hemodynamic responses were assessed in anesthetized, open-chest control (nonpregnant) and puerperium/postpartum swine at baseline and in response to intravenous infusion of dobutamine (1–30 μg/kg/min). Blood pressure and heart rate were lower in postpartum swine at baseline and in response to dobutamine (P < 0.05). Coronary blood flow and myocardial oxygen delivery were significantly diminished at baseline in postpartum swine (P < 0.001), which corresponded with ∼35% reduction in myocardial oxygen consumption (MVO2) (P < 0.001). Postpartum swine displayed enhanced retrograde coronary flow, larger cardiomyocyte area (P < 0.01) and marked capillary rarefaction (P < 0.01). The relationship between coronary blood flow and heart rate (P < 0.05) or MVO2 (P < 0.001) was significantly diminished in postpartum swine as dobutamine increased MVO2 up to ∼135% in both groups. This reduction in myocardial perfusion was associated with decreases in myocardial lactate uptake (P < 0.001), increases in coronary venous PCO2 (P < 0.01) and decreased coronary venous pH (P < 0.01). These findings suggest an impaired balance between coronary blood flow and myocardial metabolism could contribute to the increased incidence of maternal myocardial ischemia and premature death in the postpartum period.

Transthyretin Amyloid Cardiomyopathy – Setting the Diagnosis Step by Step

Introduction: Transthyretin amyloid cardiomyopathy (ATTR-CM) can be diagnosed in the absen-ce of histology with typical echocardiographic fi ndings and skeletal scintigraphy showing grade 2 or 3 myocardial tracer uptake, when clonal plasma cell dyscrasia is excluded. Aim: To present a patient diagnosed with ATTR-CM, who was hospitalized with clinical signs of congestive heart failure. Case Report: An 84-year-old man was hospitalized with clinical signs of heart failure. Echocardiography showed concentric left ventricular hypertrophy (LVH) with reduced systolic function, along with impaired LV global longitudinal strain (GLS) with apical sparing (-9.9%). Serum and urine protein electrophoresis with immunofi xation were obtained and were negative for plasma cell dyscrasia. Bone scintigraphy showed similar radiotracer uptake in the myocar-dium and ribs (Perugini grade 2). The diagnosis of ATTR-CM was confi rmed. Conclusion: ATTR-CM is an underdiagnosed condition and should be suspected in patients with heart failure and unexplained LVH.

FDG PET in a Patient on a GLP-1 Agonist/Insulin Secretagogue.

With the increase in use of GLP-1 receptor agonists such as semaglutide (Ozempic, Wegovy, Rybelsus) in the population, nuclear medicine physicians should be aware of the possibility of nondiagnostic FDG PET scans due to these medications, which work partly by increasing insulin secretion. We demonstrate a case where a patient's use of such a medication presumptively led to muscular and myocardial uptake, complicating scan interpretation considerably. Clinicians should be aware of the presence of these drugs and their potential effect on biodistribution in FDG PET. Further study is needed to best understand the effects of these medications on FDG biodistribution.

Assessment of incidental cardiac uptake in bone scintigraphy across Spain: The ECCINGO study

AimMyocardial uptake on bone scintigraphy has become useful for the detection of transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to assess the prevalence of myocardial uptake in patients over 18 years of age with no clinical suspicion of cardiac amyloidosis (CA) who had undergone bone scintigraphy. Methods and resultsThis was an observational, retrospective, multicenter study across 21 Spanish hospitals (September–November 2019). Of the 9864 scans analyzed (locally and centrally), incidental cardiac uptake was observed in 71 patients (0.72%), a prevalence that increased with age. A previous diagnosis of heart failure was found in 16.9% of patients with positive uptake, with >50% in NYHA II. ATTR-CA was diagnosed in 10 patients, with a mean delay of 10.4 months (95% CI: 5.1–15.7). All were >70 years old, primarily male, and had greater left ventricular hypertrophy than patients without a confirmed diagnosis (p<0.0001). ATTR-CA patients had higher rates of orthostatic hypotension (30.0% vs. 3.8% in non-ATTR-CA; p=0.025). ConclusionsThis is the first retrospective, national, multicenter study evaluating the prevalence of incidental cardiac uptake in bone scintigraphy performed for non-cardiac reasons, showing a prevalence of 0.72% in this population. Referral of these patients may facilitate early diagnosis of CA with a resulting benefit for patients.

Ineffective matching of oxygen supply to myocardial metabolism in primiparous compared to nulliparous swine

Maternal mortality rates in the United States are higher than any other developed country in the world. Most postpartum maternal deaths are directly related to adverse cardiovascular events and often occur in mothers who have had a healthy pregnancy. Although pregnancy is recognized as a cardiovascular stress test for the pregnant patient, understanding of how the longitudinal and dynamic cardiovascular adaptations during pregnancy contribute to augmented risk of cardiovascular complications through the postpartum period remains poorly understood. We propose that pregnancy-induced adaptations in the coronary circulation contribute to adverse cardiovascular outcomes, especially during the puerperium period (1-60 days following delivery). Accordingly, this study tested the hypothesis that the balance between coronary blood flow and myocardial metabolism is compromised in the puerperium heart. Experiments were performed in anesthetized, open-chest control nulliparous (control) and primiparous (postpartum) swine during the puerperium period (35-45 days post-delivery). Systemic and coronary hemodynamic responses were assessed under baseline conditions and in response to continuous intravenous infusion of dobutamine (1 – 30 μg/kg/min). Under baseline conditions, blood pressure averaged 107 ± 6 mmHg in both control and postpartum swine and was unaffected by dobutamine administration (P = 0.94). Heart rate increased from 77 ± 6 to 165 ± 9 beats/min in response to dobutamine in control swine vs. 52 ± 3 to 139 ± 13 beats/min in postpartum swine (P = 0.53). Coronary blood flow and myocardial oxygen delivery were significantly diminished by ~60 ± 8% at rest in postpartum swine, which is consistent with reduced myocardial oxygen consumption (MVO2). The relationship between coronary blood flow and heart rate (P &lt; 0.0001) or MVO2 (P = 0.0002) showed a marked parallel downward shift in postpartum swine at rest and in response to dobutamine infusion. This reduction in myocardial perfusion was associated with significant reductions in myocardial lactate uptake at rest in postpartum vs. control (0.34 μmol/min/g vs. 0.08 μmol/min/g, P = 0.02). Dobutamine increased myocardial lactate uptake in control by ~47 ± 3% with little change in the postpartum group. Together, these results suggest an ineffective matching of myocardial oxygen supply to metabolism in postpartum swine. This imbalance is consistent with increased incidence of myocardial ischemia and cardiac deaths in postpartum puerperium period. This work was supported by AHA.23PRE101281, NIH R01 HL158723. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Adropin Treatment Restores Cardiac Function and Metabolic Flexibility in Diabetic Cardiomyopathy

Background: Diabetic cardiomyopathy (DCM) is a major complication of diabetes, and has been recognized as a cause of heart failure independent of other common risk factors. Metabolic inflexibility is a hallmark feature, where increased free fatty acid availability and decreased myocardial glucose uptake lead to an over-reliance on fatty acid oxidation, reducing cardiac work effciency. Energetic ineffciency in diabetic hearts may have profound implications for cardiac function under conditions of increased workload, and therefore therapeutic approaches are warranted. Adropin is a liver- and brain-secreted peptide hormone shown to regulate fuel metabolism in the heart. Adropin levels are significantly reduced in obese and diabetic human subjects, and this decrease is linked to increased adiposity, insulin resistance, and impaired glucose tolerance. Our lab recently showed that acute adropin treatment restores glucose oxidation activity in the hearts of prediabetic obese mice. However, the effects of chronic adropin exposure in the heart remains unknown. Hypothesis: We hypothesize that adropin treatment will exhibit beneficial effects on cardiac fuel metabolism that may lead to long-term improvements in functional output. Methods: We used a preclinical model of DCM to investigate the effects of long-term adropin treatment on cardiac structural and metabolic remodeling. Mice were treated with adropin daily for four weeks, and subjected to echocardiography, glucose tolerance tests, histopathology, RNA-sequencing, and metabolomics. Results: We report that long-term adropin treatment restores normal cardiac structure and metabolic function in the diabetic heart, by inhibiting flux of non-oxidative glycolytic intermediates into the hexosamine biosynthetic pathway. Conclusions: Our findings highlight the therapeutic potential of adropin signaling to attenuate cardiac remodeling in DCM. The project described was supported by NIDDK 1F31DK134089 and NHLBI R01HL147861. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Incidental Myocardial Uptake in Patients with Prostate Cancer: A Challenging Subject

Background: Countless confounding factors have been described in the interpretation of incidental myocardial uptakes. Among them, prostate cancer is probably the most important. While some authors may defend the benign etiology of these uptakes, others propose a further study to rule out amyloid cardiomyopathy. Objective: Our aim is to investigate the clinical relevance of incidental myocardial uptakes in bone scans requested to evaluate prostatic neoplasia, assessing the possibility that the described uptakes correspond to cardiac amyloidosis (CA). Methods: Retrospective revision of 997 patients, 20 of which showed incidental myocardial uptake. We performed a cardiological study in these 20 patients in order to indicate whether the myocardial uptake is just attributable to prostate cancer or data suggesting CA. Results: By analysing clinical, biochemical and imaging data, 11 out of 20 of the patients had two or more Red-Flags of transthyretin amyloid cardiomyopathy (ATTR-c). In the other four cases, there was one Red-Flag suggestive of ATTR-c. Conclusions: When myocardial uptake is detected incidentally in patients with prostate cancer, it cannot be attributed to the neoplasm itself before ruling out cardiac amyloidosis. Therefore, a cardiological study must be carried out following current protocols for the diagnosis of transthyretin amyloid heart disease.

Point-of-care β-hydroxybutyrate measurement predicts adequate glucose metabolism suppression in cardiac FDG-PET/CT.

The aims of our study were to evaluate whether point-of-care β-hydroxybutyrate (BHB) measurement can be used to identify patients with adequate cardiac glucose metabolism suppression for cardiac[18F]-fluoro-2-deoxy-d-glucose-positron emission tomography with computerized tomography(FDG-PET/CT) and to develop a pretest probability calculator of myocardial suppression using other metabolic factors attainable before imaging. We recruited 193 patients with any clinical indication for whole body [18F]-FDG-PET/CT. BHB level was measured with a point-of-care device. Maximal myocardial standardized uptake value using lean body mass (SULmax) was measured from eight circular regions of interest with 1 cm circumference and background from left ventricular blood pool. Correlations SULmax and point-of-care measured BHB were analysed. The ability of BHB test to predict adequate suppression was evaluated with receiver operating characteristic analysis. Liver and spleen attenuation in computed tomography weremeasured to assess the presence of fatty liver. BHB level correlated with myocardial uptake and, using a cut-off value of 0.35 mmol/L to predict adequate myocardial suppression, we reached specificity of 90% and sensitivity of 56%. Other variables to predict adequate suppression were diabetes, obesity, ketogenic diet and fatty liver. Using information attainable before imaging, we created a pretest probability calculator of inadequate myocardial glucose metabolism suppression. The area under the curve for BHB test alone was 0.802 and was 0.857 for the pretest calculator (p = 0.319). BHB level measured with a point-of-care device is useful in predicting adequate myocardial glucose metabolism suppression. More detailed assessment of other factors potentially contributing to cardiac metabolism is needed.

Noninvasive Monitoring of Early Cardiac Fibrosis in Diabetic Mice by [68Ga]Ga-DOTA-FAPI-04 PET/CT Imaging.

Cardiac fibrosis represents one of the representative pathological characteristics in the diabetic heart. Active fibroblasts play an essential role in the progression of cardiac fibrosis. The technologies for noninvasive monitoring of activated fibroblasts still have to be investigated. The purpose of this study was to evaluate the feasibility of targeted fibroblast activation protein (FAP) molecular imaging in the early evaluation of diabetic cardiac fibrosis using [68Ga]Ga-DOTA-FAPI-04 PET/CT. PET/CT imaging was conducted in db/db mice and db/m mice at weeks 12 and 24. Diabetic heart injury was determined using echocardiography and serum biomarkers. Additionally, the levels of cardiac fibrosis were also assessed. In our study, conventional diagnostic modalities, including echocardiography and serum biomarkers, failed to monitor early-stage cardiac dysfunction and fibrosis in diabetic mice. Conversely, the results of [68Ga]Ga-DOTA-FAPI-04 PET/CT imaging demonstrated that diabetic mice had increased myocardial uptake of radioactive tracers in both early-stage and late-stage diabetes, consistent with the elevated FAP expression and increased cardiac fibrosis level. Notably, cardiac PET signals exhibited significant correlations with left ventricular ejection fractions, the E/A ratio, and the level of serum TGF-β1, PIIINP, and sST2. The results demonstrated the potential of [68Ga]Ga-DOTA-FAPI-04 PET/CT imaging for visualizing activated fibroblasts and detecting early-stage diabetic heart injury and fibrosis noninvasively. They also demonstrated the clinical superiority of [68Ga]Ga-DOTA-FAPI-04 PET/CT imaging over echocardiography and serum biomarkers in the early monitoring of diabetes-related cardiac dysfunction and fibrosis.

Use of Bone Scintigraphy in The Diagnosis of Cardiac Amyloidosis

Cardiac amyloidosis is a rare and progressive condition caused by the buildup of amyloid in the heart. There are two common forms of cardiac amyloidosis: light-chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). The deposition of amyloid in the extracellular matrix of the myocardium leads to heart failure over time, and if left untreated, it can even be fatal. For this reason, early diagnosis is essential for both prognosis and improving patients' quality of life. Since cardiac amyloidosis is a potentially treatable condition, early diagnosis is key to improving patient survival and quality of life. There is now compelling evidence showing that nuclear imaging plays a fundamental role in the non-invasive diagnosis of transthyretin cardiac amyloidosis. Due to its high sensitivity and specificity, radiotracer compounds that target the bones are considered sufficient for establishing the diagnosis, avoiding the need for endomyocardial biopsy. In this study, we analyzed data obtained from examinations conducted on patients referred to the Cardiology Department of the "San Giovanni di Dio e Ruggi d'Aragona" University Hospital, who presented with suspected cardiac amyloidosis. These patients underwent scintigraphy with 99mTc-HMDP (hydroxymethylenediphosphonate), using a large-field computerized gamma camera with a parallel-hole collimator and SPECT. After performing early whole-body planar acquisitions at 5 minutes and late acquisitions at 3 hours after intravenous administration of approximately 700 MBq of Tc-99m HMDP, myocardial uptake was observed. Subsequently, targeted acquisitions and SPECT tomographic studies were performed on the myocardial uptake areas. All acquired images were subsequently subjected to quantitative and qualitative analysis, allowing us to extract a large number of parameters reflecting morphological and predictive characteristics using radiomics and more or less automated analysis algorithms. This analysis enabled us to obtain quantitative information that is not apparent in a qualitative image analysis. The ability to extract hidden information from digital medical images is of particular interest as it can enhance the predictive capabilities of existing automatic segmentation algorithms. Extracting new information that was previously hidden can be utilized for automatic image segmentation.