Early detection of anthracycline-induced cardiotoxicity using [68 Ga]Ga-FAPI-04 imaging.

PURPOSE: Anthracycline-induced cardiotoxicity (AIC), whose major manifestation is diffuse myocardial fibrosis, is an important clinical problem in cancer therapy. Therefore, early identification and treatment are clinically important. This study aims to explore the feasibility of using 68 Ga-labelled fibroblast activation protein (FAP) inhibitor ([68 Ga]Ga-FAPI) positron emission tomography/computed tomography (PET/CT) for the early identification of the fibrotic process and guidance of antifibrosis therapy in AIC. METHODS: An AIC rat model was induced by the intravascular administration of doxorubicin (DOX) once per week for 1, 2, 3 and 6 weeks (2.5 mg/kg/injection, groups 1-4), whereas intravascular saline was administered to control rats. Experimental and control groups (n = 4) underwent [68 Ga]Ga-FAPI PET/CT following disease induction. Groups 5 and 6 received DOX injections for 3 and 6 weeks, treated with angiotensin-converting enzyme (ACE) inhibitor starting at 3 weeks, treated with enalapril (20 mg/kg, gastric gavage) daily and underwent echocardiography and [68 Ga]Ga-FAPI PET/CT at 3 weeks after treatment. Rat hearts were subjected to haematoxylin and eosin staining, FAP immunohistochemistry, Sirius red staining and Masson's trichrome staining to investigate the pathological changes and deposition of collagen fibres. Rat blood was sampled weekly for the enzyme-linked immunosorbent assay of various markers of myocardial injury, such as plasma cardiac troponin I, B-type natriuretic peptide and angiotensin II. RESULTS: [68 Ga]Ga-FAPI-04 uptake by the heart was significantly higher in the cardiotoxicity group than in the control group at weeks 3 (SUVmax: 1.21 ± 0.23 vs 0.67 ± 0.01, P < 0.05) and 6 (SUVmax: 1.48 ± 0.28 vs 0.67 ± 0.08, P < 0.001), whereas left ventricle ejection fraction (LVEF) did not significantly differ between normal and AIC rats at week 3. FAP+ expression began to increase starting at week 3, before irreversible fibrotic changes were detected, until week 6. After 3 weeks of enalapril treatment, [68 Ga]Ga-FAPI-04 accumulation decreased in groups 5 and 6 (SUVmax decreased from 1.21 ± 0.23 to 0.77 ± 0.08 and 1.48 ± 0.28 to 1.09 ± 1.06, P < 0.05). Cardiac function was preserved (LVEF was 75.7% ± 7.38% in group 3 vs 74.5% ± 2.45% in group 5, P > 0.05) and improved (LVEF increased from 51.6% ± 9.03% in group 4 to 65.2% ± 4.27% in group 6, P < 0.05), and myocardial fibrosis attenuated (from 6.5% ± 1.2% in group 4 to 4.31% ± 0.37% in group 6, P < 0.01). CONCLUSION: [68 Ga]Ga-FAPI PET/CT can be used for the early detection of active myocardial fibrosis in AIC and the evaluation of the efficacy of therapeutic interventions. Early treatment guided by [68 Ga]Ga-FAPI PET/CT may reduce anthracycline-induced myocardial injury and improve heart function.

Prognostic value of 18F-FDG PET/CT in patients with relapsed multiple myeloma.

This study aimed to assess the prognostic value of 18F-fluorodeoxyglucose positron emission tomography/computer tomography (18F-FDG PET/CT) in patients with relapsed multiple myeloma (MM). Fifty-one consecutive patients with relapsed MM were enrolled in this retrospective study. 18F-FDG parameters based on the Italian Myeloma Criteria for PET Use (IMPeTUs) and clinical data were analyzed for overall survival (OS) and progression-free survival (PFS). The Cox proportional risk model was used for univariate and multivariate analysis, and Kaplan-Meier survival curves were used for survival analysis. The median length of follow-up was 20 months (IQR, 5-29 months), the median PFS for the entire cohort was 8 months (IQR, 3-17 months) and the median OS was 21 months (IQR, 8-49 months). Multivariate survival analysis demonstrated that the Deauville score of BM > 3 [HR 2.900, 95% CI (1.011, 8.319), P = 0.048] and the presence of EMD [HR 3.134, 95% CI (1.245, 7.891), P = 0.015] were independent predictors of poor PFS. The presence of EMD [HR 12.777, 95% CI (1.825, 89.461), P = 0.010] and the reduced platelets count [HR 7.948, 95% CI (1.236, 51.099), P = 0.029] were adversely associated with OS. 18F-FDG PET/CT parameters based on IMPeTUs have prognostic significance in patients with relapsed MM.

99mTc-HFAPi SPECT Imaging Predicts Left Ventricular Remodeling After Acute Myocardial Infarction.

AIMS: This study aimed to evaluate the predictive utility of 99mTc-radiolabeled fibroblast activation protein inhibitor (99mTc-HFAPi) single-photon emission computed tomography (SPECT) imaging in post- acute myocardial infarction (AMI) patients for assessing 12-month left ventricular (LV) remodeling. METHODS: A cohort of 58 AMI patients (46 males, median age 61 [53, 67] years) underwent baseline 99mTc-HFAPi imaging (5 ± 2 days post-MI), perfusion imaging (6 ± 2 days post-MI), and echocardiography (2 ± 2 days post-MI). Additionally, 15 patients had follow-up 99mTc-HFAPi and perfusion imaging, while 30 patients had follow-up echocardiography. Myocardial 99mTc-HFAPi activity was assessed at patient level. LV remodeling was defined as a ≥10% increase in LV end-diastolic diameter (LVEDD) or LV end-systolic diameter (LVESD) from baseline to follow-up echocardiography. RESULTS: AMI patients displayed localized but non-uniform 99mTc-HFAPi uptake, exceeding perfusion defects. Baseline 99mTc-HFAPi activity exhibited significant correlations with BNPmax, LDHmax, cTNImax, and WBCmax, inversely correlating with LVEF. After 12 months, 11 patients (36.66%) experienced LV remodeling. Univariate regression analysis demonstrated an association between baseline 99mTc-HFAPi uptake extent and LV remodeling (OR= 2.14, 95%CI, 1.04, 4.39, p=0.038). CONCLUSIONS: 99mTc-HFAPi SPECT imaging holds promise in predicting LV remodeling post-MI, providing valuable insights for patient management and prognosis. LAY SUMMARY: Our study introduces 99mTc-radiolabeled fibroblast activation protein inhibitor (99mTc-HFAPi) single-photon emission computed tomography (SPECT) imaging as a potentially cost-effective modality for evaluating fibrotic process in the context of post-AMI LV remodeling. The study establishes a positive correlation between 99mTc-HFAPi activity, particularly 99mTc-HFAPi uptake extent, and LV remodeling, suggesting 99mTc-HFAPi SPECT imaging as a promising tool for risk prediction in post-AMI patients. The findings from this study have the potential to revolutionize post-AMI patient management by enabling early identification of those at risk for adverse LV remodeling. This identification could pave the way for tailored interventions, potentially improving clinical outcomes and reducing the development of heart failure.

Myocardial Activity at 18F-FAPI PET/CT and Risk for Sudden Cardiac Death in Hypertrophic Cardiomyopathy.

Background Myocardial fibrosis contributes to adverse cardiovascular events in hypertrophic cardiomyopathy (HCM). Purpose To explore the characteristics of cardiac fibroblast activation protein inhibitor (FAPI) PET/CT imaging and its relationship with the risk of sudden cardiac death (SCD) in HCM. Materials and Methods In this prospective study from July 2021 to January 2022, participants with HCM and healthy control participants underwent cardiac fluorine 18 (18F)-labeled FAPI PET/CT imaging. Myocardial FAPI activity was quantified as intensity (target-to-background uptake ratio), extent (the percent of FAPI-avid myocardium of the left ventricle [LV]), and amount (the percent of FAPI-avid myocardium of LV × target-to-background ratio). Regional wall thickness was analyzed at cardiac MRI. The 5-year SCD risk score was calculated from the 2014 European Society of Cardiology guidelines. Univariable and multivariable linear regression analyses were used to identify factors related to the FAPI amount. The correlation between FAPI amount and 5-year SCD risk was explored. Results Fifty study participants with HCM (mean age, 43 years ± 13 [SD]; 32 men) and 22 healthy control participants (mean age, 45 years ± 17; 14 men) were included. All participants with HCM had intense and inhomogeneous cardiac FAPI activity in the LV myocardium that was higher than that in healthy control participants (median target-to-background ratio, 8.8 vs 2.1, respectively; P < .001). In HCM, more segments with FAPI activity were detected than the number of hypertrophic segments (median, 14 vs five, respectively; P < .001); 84% of nonhypertrophic segments showed FAPI activity. Log-transformed FAPI amount had a positive relationship with log-transformed N-terminal probrain natriuretic peptide, high-sensitive troponin I, and left atrial diameter and a negative relationship with LV ejection fraction z-score. Degree of FAPI activity positively correlated with the 5-year SCD risk score (r = 0.32; P = .03). Conclusion Fibroblast activation protein inhibitor (FAPI) PET/CT imaging indicated intense and heterogeneous activity in hypertrophic cardiomyopathy, and FAPI uptake was associated with 5-year risk of sudden cardiac death. © RSNA, 2022 Online supplemental material is available for this article.

Functional significance of myocardial activity at 18F-FAPI PET/CT in hypertrophic cardiomyopathy identified by cardiac magnetic resonance feature-tracking strain analysis.

PURPOSE: This study aimed to evaluate the functional significance of 18F-labeled fibroblast activation protein inhibitor (18F-FAPI) activity in hypertrophic cardiomyopathy (HCM) by comparison with cardiac magnetic resonance feature-tracking (CMR-FT) strain analysis. METHODS: A total of 49 HCM patients were included in this study. Two independent control groups of healthy participants with a matched age and sex to the HCM patients were also enrolled. Left ventricular (LV) 18F-FAPI activity was analyzed for extent (FAPI%) and intensity (maximum target-to-background ratio, TBRmax). The CMR tissue characterization parameters of the LV included late gadolinium enhancement, native T1 value, and extracellular volume fraction. LV strain analysis was performed in radial, circumferential, and longitudinal peak strains (PS). RESULTS: Intense LV myocardial 18F-FAPI uptake was observed in HCM patients, whereas no obvious uptake was detected in healthy participants (median TBRmax, 9.1 vs. 1.2, p < 0.001). The strain parameters of HCM patients, compared with healthy participants, were significantly impaired (mean radial PS, 23.5 vs. 36.0, mean circumferential PS, -14.5 vs. -20.0, and mean longitudinal PS, -9.9 vs. -16.0, all p < 0.001). At segmental levels, there was a moderate correlation between 18F-FAPI activity and strain parameters. The number of positive 18F-FAPI uptake segments (n = 653) was higher than that of hypertrophic segments (n = 190) and positive CMR tissue characterization segments (n = 525) (all p < 0.001). In segments with negative CMR tissue characterization findings, the strain capacity of positive 18F-FAPI uptake segments was lower than that of negative 18F-FAPI uptake segments (median radial PS, 30.5 vs. 36.1, p = 0.026 and median circumferential PS, -18.4 vs. -19.7, p = 0.041). CONCLUSION: 18F-FAPI imaging can partially reflect the potential strain reduction in HCM patients. 18F-FAPI imaging detects more involved myocardium than CMR tissue characterization techniques, and the additionally identified myocardium has impaired strain capacity.

Pulmonary artery imaging with 68 Ga-FAPI-04 in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: The feasibility and significance of imaging pulmonary artery (PA) remodeling with 68 Ga-fibroblast activating protein inhibitor (FAPI) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) have not yet been addressed. METHODS: 68 Ga-FAPI-04 uptake in the PA and ascending artery was evaluated in 13 patients with CTEPH and 13 matched non-CTEPH controls. The correlations of PA 68 Ga-FAPI-04 uptake and remodeling parameters derived from right heart catheterization (RHC) were analyzed. RESULTS: Of the 13 patients with CTEPH, nine (69%) showed visually enhanced 68 Ga-FAPI-04 uptake, whereas none of the control subjects had increased 68 Ga-FAPI-04 uptake in the PA. The prevalence of enhanced uptake in the main, lobar, and segmental PAs was 45% (17/38), 33% (16/48), and 28% (44/159), respectively. 68 Ga-FAPI-04 activity in the PA was positively correlated with pulmonary arterial diastolic pressure (r = 0.571, P = 0.041). CONCLUSION: 68 Ga-FAPI-04 has the potential for imaging fibroblast activation in the PA wall, and 68 Ga-FAPI-04 activity in PA is positively correlated with pulmonary arterial diastolic pressure.

Value of rest 18F-FDG myocardial imaging in the diagnosis of obstructive coronary artery disease in Chinese patients with suspected unstable angina: A prospective real-world clinical study.

BACKGROUND: This study aimed to determine the clinical value of rest 18F-FDG imaging in Chinese patients with non-acute chest pain, normal ECG, negative troponin, and suspected UA. METHODS: 136 patients were prospectively included and underwent rest 18F-FDG PET imaging and coronary arteriography within 1 week. RESULTS: Obstructive CAD was diagnosed in 71 patients, and stenosis ≥ 70% was confirmed in 130 vascular territories. At patients and vascular level, rest 18F-FDG imaging showed sensitivity of 62.0%, 47.7%, specificity of 92.3%, 94.2%, accuracy of 76.5%, 79.4%, PPV of 89.8% and 79.5%, and NPV of 69.0% and 79.4%. The AUCs were 0.771 and 0.710. Of 71 patients with obstructive CAD, rest 18F-FDG imaging showed sensitivity of 47.7% and 58.8%, specificity of 91.6% and 91.2%, accuracy of 64.8% and 80.4%, PPV of 89.9% and 76.9% and NPV of 52.8% and 81.6% in all vascular level and single-vessel disease. In patients with two- or three-vessel disease, rest 18F-FDG imaging had a diagnostic sensitivity, specificity, accuracy, PPV, and NPV of 43.8%, 93.3%, 50.5%, 97.7%, and 20.6%. The AUCs were 0.696, 0.750, and 0.685. CONCLUSION: Rest 18F-FDG imaging performed certain overall diagnostic efficiency for obstructive CAD in Chinese patients with suspected UA, especially the excellent high PPV in identifying culprit ischemic territory in patients with multivessel disease.

Fibroblast activation protein imaging in atrial fibrillation: a proof-of-concept study.

BACKGROUND: To evaluate the feasibility of using radiolabeled fibroblast activation protein inhibitor (FAPI) PET/CT imaging to assess activated fibroblasts in the atria of individuals with AF and to identify factors contributing to enhanced atrial activity. METHODS: We constructed left atrial appendage (LAA) pacing beagle dog AF models (n = 5) and conducted 18F-FAPI PET/CT imaging at baseline and eight weeks after pacing. Right atrial (RA) specimens were collected from these models. Additionally, 28 AF patients and ten age- and sex-matched healthy volunteers underwent 18F-FAPI PET/CT imaging. RESULTS: RA of AF beagles showed increased 18F-FAPI uptake. Among AF patients, 18 out of 28 (64.3%) exhibited enhanced atrial FAPI activity. No atrial 18F-FAPI uptake was observed in the sham beagle and healthy volunteers. In animal RA specimens, 18F-FAPI activity correlated positively with FAP mRNA (r = .98, P = .002) and protein (r = .82, P = .03) levels, as well as collagen I mRNA expression (r = .85, P = .02). B-type natriuretic peptide levels were associated with atrial 18F-FAPI activity (OR = 3.01, P = .046). CONCLUSION: This proof-of-concept study suggests that 18F-FAPI PET/CT imaging may be a feasible method for evaluating activated fibroblasts in the atria of AF patients.

Skull metastasis is a poor prognostic factor for prostate cancer patients with bone metastasis: a retrospective study based on a Chinese population.

BACKGROUND: Skull is a relatively rare metastasis site for prostate cancer (PCa). There is no evidence regarding the prognostic indication of skull metastasis (SM) in PCa patients. In this study, we analyzed the prognostic value of SM for metastatic PCa patients receiving androgen deprivation therapy (ADT). METHODS: 107 consecutive patients were included from September 2008 to August 2021. All patients were administered with standard ADT. Abiraterone plus glucocorticoid and/or docetaxel chemotherapy were given after failure to castration-resistant prostate cancer. Clinical parameters and follow-up prognostic data were retrospectively analyzed. The association of clinical and pathological parameters with SM were analyzed. The progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier analysis and Cox regression analyses. RESULTS: Patients with SM (n = 26) had significantly higher biopsy Gleason scores, higher clinical T stage, higher prostate-specific antigen level at diagnosis, and were more likely to have high-burden metastasis and lymph node metastasis, compared with those without SM (n = 81). They also showed significantly lower level of hemoglobin, albumin and serum calcium, along with higher level of alkaline phosphatase. SM was significantly associated with shorter medium PFS (9.4 vs. 18.3 months, p < 0.001) and OS (22.2 vs. 58.2 months, p < 0.001). Cox analysis demonstrated that SM was an independent risk factor for shorter PFS (hazard ratio 2.327 [1.429-3.789], p = 0.001) and shorter OS (hazard ratio 2.810 [1.615-4.899], p < 0.001). CONCLUSION: In this study, we found that SM was significantly correlated with more aggressive disease and indicated poor prognosis in PCa patients with bone metastasis. Our study may provide useful reference for the risk stratification of PCa patients.

Echocardiographic Characteristics of Pulmonary Artery Intimal Sarcoma: Comparison With CTPA.

OBJECTIVES: This study examined the echocardiographic characteristics of patients with pulmonary artery intimal sarcoma (PAIS) and compared the results with those from computed tomographic pulmonary angiography (CTPA). METHOD: Twenty-six (26) patients were diagnosed with PAIS at the current institution during the study period, and 23 were eligible for analysis. Echocardiography and CTPA examinations were performed in all enrolled patients. RESULTS: The echocardiography results showed that most lesions had expansive growth in the left pulmonary artery (PA); the right PA; or a combination of the left PA, right PA, and main PA, with extension to the pulmonary valve and/or right ventricular outflow tract. These lesions also had distinctive sieve-like echogenic signals. Echocardiography also showed that some lesions had lobulated shapes, were nearly round and echolucent or with calcifications, and moved during imaging. The lesion distribution was similar in CTPA and echocardiography (p=0.361), but CTPA was more sensitive in detection of the complete shape (p=0.023). CONCLUSIONS: The unique echocardiographic characteristics of PAIS, especially the "sieve sign", could help in the diagnosis of this cancer. Transthoracic echocardiography is a non-invasive technique that appears effective in detecting PAIS.

Imaging of cardiac fibroblast activation in patients with chronic thromboembolic pulmonary hypertension.

PURPOSE: The aim of this study was to explore the association of cardiac fibroblast activation with clinical parameters and cardiovascular magnetic resonance (CMR) imaging parameters in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Thirteen CTEPH patients were prospectively enrolled. All of the patients underwent cardiac 68Gallium-labelled fibroblast activation protein inhibitor (68 Ga-FAPI-04)-positron emission tomography/computed tomography (PET/CT), right heart catheterisation, and echocardiography, and 11 of them additionally underwent CMR. Thirteen control subjects were selected to establish the normal range of cardiac 68 Ga-FAPI-04 uptake. Cardiac 68 Ga-FAPI-04 uptake higher than that in the blood pool was defined as abnormal. The global and segmental maximum standardised uptake values (SUVmax) of the right ventricle (RV) were measured and further expressed as target-to-background ratio (TBRRV) with left ventricular lateral wall activity as background. Late gadolinium enhancement (LGE) was visually evaluated, and native-T1 times, enhanced-T1 times, and extracellular volume (ECV) were quantitatively measured. RESULTS: Ten CTEPH patients (77%) had abnormal 68 Ga-FAPI-04 uptake in RV, mainly located in the free wall, which was significantly higher than that in controls (TBRRV: 2.4 ± 0.9 vs 1.0 ± 0.1, P < 0.001). The TBRRV correlated positively with the thickness of RV wall (r = 0.815, P = 0.001) and inversely with RV fraction area change (RVFAC) (r = - 0.804, P = 0.001) and tricuspid annular plane systolic excursion (TAPSE) (r = - 0.678, P = 0.011). No correlation was found between 68 Ga-FAPI-04 activity and CMR imaging parameters. CONCLUSION: Fibroblast activation in CTEPH, measured by 68 Ga-FAPI-04 imaging, is mainly localised in the RV free wall. Enhanced fibroblast activation reflects the thickening of the RV wall and decreased RV contractile function.

Fibroblast activation protein imaging in reperfused ST-elevation myocardial infarction: comparison with cardiac magnetic resonance imaging.

PURPOSE: The aim of this study was to explore the correlation of 18F-labeled fibroblast activation protein inhibitor (FAPI) and cardiovascular magnetic resonance (CMR) parameters in ST-elevation myocardial infarction (STEMI) patients with successful primary percutaneous coronary intervention (PPCI) and to investigate the value of FAPI imaging in predicting cardiac functional recovery, as well as the correlation between FAPI activity and circulating fibroblast activation protein (FAP) and inflammatory biomarkers. METHODS: Fourteen first-time STEMI patients (11 men, mean age: 62 ± 11 years) after PPCI and 14 gender-matched healthy volunteers (10 men, mean age: 50 ± 14 years) who had completed FAPI imaging and blood sample collection were prospectively recruited. All patients underwent baseline FAPI imaging (6 ± 2 days post-MI) and CMR (8 ± 2 days post-MI). Ten patients had follow-up CMR (84 ± 4 days post-MI). Myocardial FAPI activity was analyzed for extent (the percentage of FAPI uptake volume over the left ventricular volume, FAPI%), intensity (target-to-background uptake ratio, TBRmax), and amount (FAPI% × TBRmax). Late gadolinium enhancement (LGE), T2-weighted imaging (T2WI), extracellular volume (ECV), microvascular obstruction (MVO), and cardiac function from CMR imaging were analyzed. Blood samples obtained on the day of FAPI imaging were used to assess circulating FAP, TGF-ß1, TNF-α, IL-6, and hsCRP in STEMI patients and controls. RESULTS: Localized but inhomogeneous FAPI uptake was observed in STEMI patients, which was larger than the edematous and infarcted myocardium, whereas no uptake was detected in controls. The MVO area showed lower FAPI uptake compared with the surrounding myocardium. FAPI activity was associated with the myocardial injury biomarkers T2WI, LGE, and ECV at both per-patient and per-segment levels (all p < 0.05), but was not associated with circulating FAP, TGF-ß1, TNF-α, IL-6, or hsCRP. Among the CMR parameters, T2WI had the greatest correlation coefficient with both FAPI% and FAPI% × TBRmax. Baseline TBRmax was inversely correlated with the follow-up left ventricular ejection fraction (LVEF) (r = - 0.73, p = 0.02). CONCLUSION: FAPI imaging detects more involved myocardium than CMR in reperfused STEMI, and is associated with myocardial damage and follow-up LVEF.

Prognostic value of cardiac inflammation in ST-segment elevation myocardial infarction: A 18F-fluorodeoxyglucose PET/CT study.

BACKGROUND: 18F-fluorodeoxyglucose (FDG) imaging is used to detect cardiac inflammation and predict functional outcome in acute myocardial infarction (MI). However, data on the correlation of post-MI acute cardiac inflammation evaluated by 18F-FDG imaging and major adverse cardiac events (MACE) are limited. Therefore, we sought to explore the prognostic value of cardiac 18F-FDG imaging in patients with acute ST-segment elevation MI (STEMI). METHODS: Thirty-six patients with STEMI underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) 5 days after primary percutaneous coronary intervention. 18F-FDG activity in infarcted and remote regions, as well as peri-coronary adipose tissue (PCAT), were measured and expressed as the maximum standardized uptake value (SUVmax). Patients were followed to determine the occurrence of MACE. RESULTS: The infarcted myocardium had a higher 18F-FDG intensity than the remote area. Moreover, the PCAT of culprit coronary arteries showed a higher 18F-FDG uptake than that of non-culprit arteries. Multivariate Cox regression analysis showed that increased SUVmax of PCAT [HR 5.198; 95% CI (1.058, 25.537), P = .042] was independently associated with a higher risk of MACE. CONCLUSIONS: Enhanced PCAT activity after acute MI is related to the occurrence of MACE, and 18F-FDG PET/CT plays a promising role in providing prognostic information in patients with STEMI.

Association of atrial 18F-fluorodeoxyglucose uptake and prior ischemic stroke in non-atrial fibrillation patients.

BACKGROUND: Atrial cardiomyopathy has gained increasing attention in the field of ischemic stroke due to its prothrombotic substrate. Timely identification of high-risk individuals without atrial fibrillation (AF) is essential in secondary prevention. We sought to explore the feasibility of atrial 18F-fluorodeoxyglucose (FDG) imaging in detecting diseased atrial substrate and in identifying ischemic stroke in a non-AF population. METHODS: 1444 non-AF inpatients were initially identified. Among them, 196 patients had enhanced atrial FDG uptake, while 392 patients without atrial activity were selected as controls. Atrial activity, the history of ischemic stroke, and atrial cardiomyopathy were analyzed. RESULTS: Patients with atrial cardiomyopathy had a higher prevalence of enhanced atrial activity (47.1% vs 26.0%, P < .001), and patients with increased atrial activity had a higher prevalence of a prior history of ischemic stroke (12.2% vs 3.3%, P < .001). Multivariate regression analysis demonstrated that atrial activity was independently related to ischemic stroke after adjustment for risk factors (OR 4.02, 95% CI 1.97-8.19, P < .001) and atrial cardiomyopathy (OR 3.63, 95% CI 1.51-8.74, P = .004). CONCLUSIONS: This study identified an association between atrial FDG activity and a history of ischemic stroke and atrial cardiomyopathy in non-AF individuals. Further longitudinal study is warranted to demonstrate their causal relationship.

Longitudinal evaluation of diastolic dyssynchrony by SPECT gated myocardial perfusion imaging early after acute myocardial infarction and the relationship with left ventricular remodeling progression in a swine model.

BACKGROUND: Left ventricular diastolic dyssynchrony (LVDD), a dyssynchronous relaxation pattern, has been known to develop after myocardial damage. We aimed to evaluate the dynamic changes in LVDD in the early stage of acute myocardial infarction (AMI) by phase analysis of 99mtechnetium methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography (SPECT) gated myocardial perfusion imaging (GMPI) and explore its relationship with the progression of left ventricular remodeling (LVR). METHODS: The left anterior descending coronary arteries of 16 Bama miniature swine were occluded with a balloon to build AMI models. Animals were imaged by SPECT GMPI before AMI and at 1 day, 1 week and 4 weeks after AMI, and quantitative analysis was performed to determine the extent of left ventricle (LV) perfusion defects, left ventricular systolic dyssynchrony (LVSD) and the LVDD parameters: phase histogram bandwidth (PBW) and phase standard deviation (PSD). Echocardiography was simultaneously applied to evaluate left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and the LVDD parameters: Te-12-diff and Te-12-SD. Myocardial injury markers were measured, and 12-lead ECGs were performed. The degree of LVR progression was defined as ΔLVESV (%) = (LVESVAMI4weeks - LVESVAMI1day)/LVESVAMI1day. RESULTS: Thirteen swine completed the study. LVDD parameters changed dynamically at different time points after AMI. LVDD occurred as early as 1 day after AMI, peaked at 1 week, and trended toward a partial recovery at 4 weeks. Phase analysis on SPECT GMPI showed a significant correlation with tissue Doppler imaging for the assessment of LVDD during the longitudinal evaluation (r = 0.569 to 0.787, both P <0.05). During the univariate and multivariate regression analyses, the LVDD parameters PBW and PSD as of 1 day after AMI were significantly associated with the progression of LVR, respectively (PBW, ß = 0.004, 95% CI 0.001 to 0.007, P = 0.024; PSD, ß = 0.008, 95% CI 0.000 to 0.017, P = 0.049). Adjusted smooth curve fitting and threshold effect analysis indicated PBW and PSD break-point values of 142° and 60.4°, respectively, to predict the progression of LVR after AMI. CONCLUSIONS: Phase analysis of SPECT GMPI can accurately and reliably characterize LVDD. LVDD occurred on the first day after AMI, reached its peak at 1 week, and partially recovered at 4 weeks after AMI. LVDD as evaluated by phase analysis of SPECT GMPI early after AMI was significantly associated with the progression of LVR. The early assessment of LVDD after AMI may provide helpful information for predicting the progression of LVR in the future.

Incremental value of epicardial fat volume to coronary artery calcium score and traditional risk factors for predicting myocardial ischemia in patients with suspected coronary artery disease.

BACKGROUND: Epicardial fat volume (EFV) has been reported to be associated with coronary artery disease (CAD). CAD is the leading cause of myocardial ischemia and myocardial ischemia is closely related to major adverse cardiovascular events. We hypothesized that EFV could provide incremental value to traditional risk factors and coronary artery calcium score (CACS) in predicting myocardial ischemia in Chinese patients with suspected CAD. METHODS: We retrospectively studied 204 Chinese patients with suspected CAD who underwent single-photon emission computerized tomography-myocardial perfusion imaging (SPECT-MPI) combined with computed tomography (CT). Pericardial contours were manually defined, and EFV was automatically calculated. A reversible perfusion defect with summed difference score (SDS) ≥ 2 was defined as myocardial ischemia. RESULTS: The myocardial ischemia group had higher EFV than normal MPI group (137.80 ± 34.95cm3 vs. 106.63 ± 29.10 cm3, P < .001). In multivariable logistic regression analysis, high EFV was significantly associated with myocardial ischemia [odds ratio (OR): 8.30, 95% CI: 3.72-18.49, P < .001]. Addition of EFV to CACS and traditional risk factors could predict myocardial ischemia more effectively, with larger AUC .82 (P < .001), positive net reclassification index .14 (P = .04) and integrated discrimination improvement .14 (P < .001). The bootstrap resampling method (times = 500) was used to internally validation and calculate the 95% confidence interval (CI) of the AUC (95% CI .75-.87). The calibration curve for the probability of myocardial ischemia demonstrated good agreement between prediction and observation. CONCLUSIONS: In Chinese patients with suspected CAD, EFV was significantly associated with myocardial ischemia, and improved prediction of myocardial ischemia above traditional risk factors and CACS.

Combining body mass index with waist circumference to assess coronary microvascular function in patients with non-obstructive coronary artery disease.

BACKGROUND: Coronary microvascular dysfunction (CMD) may precede clinically overt coronary artery disease (CAD). Overall and central obesity (CO) are major risk factors for CAD. This study sought to investigate the subclinical significance of body adiposity patterns based on the CMD risk. METHODS: A total of 128 patients with non-obstructive CAD were prospectively enrolled. Patients were categorized into 4 anthropometric groups: normal weight and non-CO (NWNCO, n = 41), normal weight and CO (NWCO, n = 20), excess weight and non-CO (EWNCO, n = 26), and excess weight and CO (EWCO, n = 41). Patients underwent rest/stress electrocardiography-gated 13N-ammonia positron emission tomography to measure absolute myocardial blood flow (MBF), myocardial flow reserve (MFR), hemodynamic parameters, and cardiac function. RESULTS: Resting MBF did not differ between groups (P = .36). Compared with the NWNCO group, hyperemic MBF and MFR were significantly lower in the NWCO and EWCO groups. Notably, patients with NWCO presented the lowest hyperemic MBF and MFR and the highest incidence of CMD. Waist circumference was an independent risk factor for CMD (OR 1.05, 95% CI 1.01 to 1.10, P = .02). CONCLUSION: In patients with non-obstructive CAD, CO may be associated with an increased risk of CMD to better fit the study findings which did not assess management or monitoring of MBF and MFR.

Clinical Features and Outcomes of Pulmonary Artery Sarcoma.

OBJECTIVES: A retrospective cohort study was designed to describe the clinical features and outcomes of pulmonary artery sarcoma (PAS). METHODS: Twenty-two (22) consecutive patients diagnosed with PAS by pathological examination were enrolled and followed up until they died or until January 2020. The medical records were retrospectively reviewed to evaluate the clinical characteristics, image findings, and outcomes. RESULTS: 1) Twenty-one (21, 95.5%) patients were firstly misdiagnosed. Dyspnoea was the most common presenting symptom (19 of 22, 86.4%). 2) Filling defects in the right pulmonary artery were seen in 17 patients (77.3%) with computed tomography pulmonary angiography or magnetic resonance pulmonary angiography. Among those patients, 14 underwent positron emission tomography-computed tomography detection and 13 (92.9%) were found to have increased uptake value in the pulmonary artery. 3) The median survival (from diagnosis to death or January 2020) of the total series was 11.6 months (range, 0.7-68.5 months). The estimated cumulative survival rates at 1, 2, and 3 years were 52.6%, 32.8%, and 19.7%, respectively. Patients who received surgery and/or chemo-radiotherapy treatment had a better survival rate compared with patients without treatment (the estimated cumulative survival rates at 1, 2, and 3 years were 60.3%, 39.1%, and 29.3%, respectively, vs 33.3%, 16.6%, and 0, accordingly) and better survival time (median survival 17.02 vs 3.16 months, respectively) (p=0.025). CONCLUSIONS: Pulmonary artery sarcoma is easily misdiagnosed, as the symptoms and routine image detection are nonspecific. Positron emission tomography-computed tomography may be helpful in diagnosis. Surgery and/or chemo-radiotherapy offer a chance for better outcomes.

Incremental value of myocardial wall motion and thickening to perfusion alone by gated SPECT myocardial perfusion imaging for viability assessment in patients with ischemic heart failure.

PURPOSE: The objective of this study was to assess the incremental value of myocardial wall motion and thickening compared with perfusion alone obtained from gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in diagnosing myocardial viability in patients with ischemic heart failure. METHODS: Eighty-three consecutive patients with ischemic heart failure who underwent both 99mTc-MIBI gated SPECT MPI and 18F-FDG positron emission tomography (PET) myocardial metabolic imaging were retrospectively enrolled. SPECT/PET myocardial viability was defined as the reference standard. Segmental myocardial perfusion, wall motion, and thickening were measured by an automated algorithm from gated SPECT MPI. Univariate and stepwise multivariate analysis were conducted to establish an optimal multivariate model for predicting hibernating myocardium and scar. RESULTS: Among the 1411 segments evaluated, 774 segments had normal perfusion and 637 segments had decreased perfusion. The latter were classified by 18F-FDG PET into 338 hibernating segments and 299 scarred segments. The multivariate regression analysis showed that the model that combined myocardial perfusion uptake with wall motion and thickening scores had the optimal predictive efficiency to distinguish hibernating myocardium from scar in the segments with decreased perfusion. The model had the largest C-statistic (0.753 vs 0.666, P < 0.0001), and the global chi-square was increased from 53.281 to 111.234 when compared with perfusion alone (P < 0.001). CONCLUSIONS: Assessment of myocardial wall motion and thickening in addition to conventional perfusion uptake in the segments with decreased perfusion enables better differentiation of hibernating myocardium from scar in patients with ischemic heart failure. Considering wide availability and high cost-effectiveness, regional myocardial function integrated with perfusion on gated SPECT MPI has great promise to become a clinical tool in the assessment of myocardial viability.

Myocardial Glucose Metabolism Is Increased in Newly Diagnosed Lung Adenocarcinoma.

BACKGROUND: Cardiac metabolism alterations may be involved in abnormalities of cancer patients' cardiovascular system. This study aimed to explore whether left ventricular myocardial glucose metabolism is altered and its related factors in newly diagnosed patients with lung adenocarcinoma (LAD) who underwent fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). METHODS: From our 18F-FDG PET/CT imaging database, 171 patients with newly diagnosed LAD and 43 nononcologic subjects with matched age and sex were retrospectively analyzed. The included patients underwent conventional 18F-FDG PET/CT imaging with a >12-h fasting before 18F-FDG administration. The standardized uptake values (SUVs) of the left ventricular (LV) myocardium, arterial wall, epicardial adipose tissue (EAT), spleen, and bone marrow were separately measured. Laboratory parameters and echocardiographic results were collected as well. LAD patients were divided into 2 groups based on the 95th percentile of LV maximal SUV (SUVmax) obtained from the 43 nononcologic subjects. Univariate analysis and multiple logistic regression analysis were used to identify significant factors. RESULTS: Higher LV SUVmax was found (3.8 [2.4, 7.7] vs. 3.0 [2.0, 5.4], p = 0.052) in LAD than that in nononcologic patients, whereas no significant differences of 18F-FDG uptake were found in the arterial wall, EAT, spleen, or bone marrow between LAD patients and controls. The maximum diameter (Dmax) of the LAD lesion, SUVmax of spleen, and SUVmax of EAT were related to LV SUVmax in LAD. CONCLUSIONS: Myocardial glucose metabolism is increased in patients with newly diagnosed LAD. Dmax of LAD lesion, spleen activity, and EAT activity contribute to the increased LV activity in LAD.