Cardiac Positron Emission Tomography Research Articles

Multimodality imaging in cardiac masses

Abstract Background Cardiac masses (CM) are an extremely heterogeneous clinical scenario, including benign and malignant neoformations. After a first echocardiographic assessment, Cardiac Computed Tomography (CCT) together with Cardiac Magnetic Resonance (CMR) and 18-Fluorodeoxyglucose Positron Emission Tomography (18- FDG-PET) represent second line and third-line imaging techniques to determine the nature of the mass. However, data regarding their diagnostic performance and a standardized imaging algorithm are lacking. Purpose To evaluate the different roles of CCT, CMR, and PET in defining the nature of CMs and to propose an evidence-based, stepwise, diagnostic approach. Materials and methods Out of 312 patients with suspected mass from January 2000 and August 2022, we enrolled 87 patients who underwent CCT, CMR and 18-FDG-PET within a month from the initial evaluation. A definitive diagnosis was achieved by histological examination or, in case of cardiac thrombi, with radiological evidence of thrombus resolution after an appropriate anticoagulant treatment. For each imaging technique, we identified a model with the strongest predictors of malignancy at multivariate analysis and evaluated their ability to discriminate between benign and malignant neoformations. A multiple model with forwarding selection was performed to identify the strongest predictors of malignancy at CCT, CMR and 18-FDG-PET. Results CCT model included 4 variables (irregular margins, mass dimension, invasiveness, and not-hypodense lesion) with an Area Under the Curve (AUC) of 0.972, 95% Confidence Interval (CI) 0.94-1.0; CMR model included 3 parameters (invasiveness, pericardial effusion and irregular margins, AUC 0.976 with 95% CI 0.95-1.0); PET model included only cardiac maximum Standardized Uptake Value (SUVmax), with an AUC 0.87 (95% CI 0.74-0.971). When implemented with SUVmax, CCT and CMR models showed only a slight improvement in their discrimination ability (AUC 0.975 and 0.986, respectively). No statistical difference was observed between CCT and CMR models regarding their discrimination ability (AUC 0.972 vs 0.976, p=0.26). However, on a multiple model with forwarding selection evaluating CCT, CMR and PET variables, only the 3 MR parameters remained significant predictors of malignancy. Conclusion After a first echocardiographic assessment, the application of the CMR model may be the most accurate second-level investigation to discriminate between benign and malignant lesions. When CMR is not available, or the patient has contraindications to CMR, the CCT model performs similarly, and 18-FDG-PET provides a negligible advantage.

Abstract 18949: Bariatric Surgery is Associated With Improved Coronary Microvascular Function and Cardiorespiratory Fitness in Patients With Ischemia and Non-Obstructive Coronary Arteries (INOCA)

Introduction - Severe obesity is associated with cardiometabolic disease and coronary microvascular dysfunction, as reflected by impaired coronary flow reserve (CFR). Bariatric surgery promotes sustained weight loss and lower incidence of diabetic microvascular complications, but its effect on the coronary microcirculation is unclear. In this ongoing pilot study, we aimed to investigate the impact of bariatric surgery on CFR, endothelial function, and cardiorespiratory fitness in patients with severe obesity and INOCA. Methods - Consecutive patients (N=19) with severe obesity (BMI≥35 kg/m 2 ), exertional dyspnea and planned bariatric surgery were enrolled. Patients underwent cardiac stress positron emission tomography (PET), peripheral arterial tonometry (PAT), echocardiogram and cardiopulmonary exercise testing (CPET) at baseline and after a median of 6.2 months post-surgery (N=9 completed to date). CFR was quantified as stress/rest myocardial blood flow (MBF) from PET. Reactive hyperemia index (RHI), a marker of endothelial function, was calculated as the ratio between PAT signal post and pre-occlusion in the corresponding arm. Results - Median age was 50 (Q1-Q3 42-54) years and 63% were female. At baseline, median BMI was 43 (40-54), LVEF was 0.62, and %LV visual ischemia was 0. Higher BMI inversely correlated with CFR (r= -0.53, p=0.02). As compared to baseline, patients post-surgery (78% sleeve gastrectomy, 22% gastric bypass) had significantly decreased BMI (45.2 vs. 34.3, p=0.008) and improved stress MBF [1.8 (1.3-2.2) vs. 2.4 (1.8-2.8), p<0.02], CFR [2.3 (1.9-2.6) vs. 3.1 (2.4-3.6), p<0.02] and peripheral endothelial function [RHI 1.5 (1.4-1.8) vs. 2.4 (1.8-2.8) vs. p=0.04]. These changes were accompanied on CPET by significantly higher exercise workload [112 (84.2-146) vs. 124.5 (90.5-149) W, p=0.046] and relative peak VO 2 [12.5 (11.9-14) vs. 15.2 (12.6-17) mL/kg/min, p=0.028]. Higher stress MBF directly correlated with relative peak VO 2 (r=0.53, p=0.04). Conclusion - In this pilot clinical study, bariatric surgery was associated with significant improvements in coronary microvascular function, peripheral endothelial function, and cardiorespiratory fitness in symptomatic patients with severe obesity after six months.

Abstract 17852: A Right Atrial Mass(querader) Causing Complete Heart Block in an Otherwise Healthy Female

Introduction: Right atrial masses are ominous and have a broad differential including thrombus, primary cardiac tumors such as myxoma vs sarcoma, metastatic processes like lymphoma, and, rarely, autoimmune etiologies. In this case, an apple watch notification of bradycardia was a simple start to a complicated course of rapidly progressive conduction disease arising from an unusual presentation of cardiac sarcoidosis. Case Presentation: A 45-year-old previously healthy female originally presented to clinic with a one-month history of exertional dyspnea and palpitations with bradycardia noted on her Apple Watch and an ongoing event monitor revealing transient type II second-degree atrioventricular block. In the office, she was normotensive but bradycardic at 33 beats per minute with electrocardiogram revealing complete heart block with junctional escape. She was admitted for additional work-up with transesophageal echocardiogram (TEE) which was unrevealing. Cardiac magnetic resonance imaging (cMRI) identified two 2 x 2 cm right atrial masses that appeared hypermetabolic on cardiac fluorodeoxyglucose positron emission tomography (FDG cPET) in addition to bilateral hilar lymph nodes. A temporary-permanent pacemaker equipped with a lead capable of floating atrial bipolar sensing was placed while biopsy plans were arranged. Transbronchial ultrasound guided biopsy of the hilar lymph node returned benign. She then underwent two different attempts at transcatheter biopsy of the right atrial masses - one TEE guided, another intracardiac echo (ICE) guided - with most samples unrevealing except one with an inconclusive amount of spindle cells raising concerns for sarcoma. The decision was made to pursue cardiothoracic surgical resection of the right atrial masses with pathology returning with granulomatous lesions consistent with sarcoidosis. Discussion: Cardiac involvement is present in 25% of cases of sarcoidosis and most commonly manifests as conduction abnormalities, ventricular arrhythmia, and/or heart failure. Only a few cases of atrial masses are reported in the literature and its presence in this woman with heart block confounded the picture before a diagnostic biopsy of this treatable condition could be obtained.

Abstract 19124: Systemic Sclerosis Masquerading as Heart Failure

Cardiac disease occurs in 80% of patients with systemic sclerosis (SS). Patients may present with various symptoms, including dyspnea, palpitations, chest pain, and heart failure. Of these, systolic heart failure has the rarest prevalence, estimated between 1-5% of patients. The mechanism behind myocardial damage is still unclear. Current literature supports a fibrotic process due to ischemic necrosis and reperfusion damage. There is a lack of representation of SS-related cardiac disease, but it is crucial to recognize it early for prompt intervention. A 62-year-old male with a history of diastolic dysfunction presented with acute hypoxic respiratory failure. A transthoracic echocardiogram demonstrated a new severely reduced systolic function at 20%. Angiogram demonstrated non-obstructive coronary artery disease. Further autoimmune workup revealed a significantly elevated ANA and highly positive RNA polymerase III antibody. The patient underwent a cardiac magnetic resonance imaging (MRI) scan, which showed evidence of inflammation with diffuse myocardial fibrosis concerning an infiltrative process. Subsequent cardiac positron emission tomography (PET) showed increased uptake in the basal portions of the septum and anterior wall for myocarditis. Given his autoimmune workup results and imaging, the patient was subsequently diagnosed with rapidly progressive cutaneous systemic sclerosis and associated non-ischemic cardiomyopathy. The patient was started on goal-directed medical therapy, including losartan, spironolactone, metoprolol, and empagliflozin. Additionally, he started on mycophenolate mofetil for immunosuppression. Roughly six months after discharge, his pulmonary function tests remain stable. His ejection fraction improved to 62%. Roughly one-third of systemic sclerosis-related deaths are due to cardiac involvement. Yet, most patients are asymptomatic during the early stages, with a variable phenotype later in disease progression. We report a case of a patient who developed systemic sclerosis-related myocarditis with an initial presentation of acute systolic heart failure. His cardiac dysfunction recovered from optimal goal-directed therapy and immunosuppression.

Abstract 16126: Sex Differences in the Relationship Between Left Ventricular Global Longitudinal Strain and Abnormal Myocardial Flow Reserve in a Patient Population With Sleep Disordered Breathing

Introduction: Obstructive sleep apnea (OSA), a form of sleep disordered breathing (SDB), is associated with abnormal myocardial flow reserve (MFR), a precursor to heart failure with preserved ejection fraction (HFPEF). Sex differences have been reported in the prevalence of abnormal MFR and OSA. However, it is unknown if there are sex differences in the relationship between left ventricular (LV) global longitudinal strain (GLS) and abnormal MFR in a patient population with SDB. Methods: We compared LV GLS among patients in our institution who had sleep testing for obstructive sleep apnea (OSA), cardiac PET stress test and an echocardiogram between 2015 and 2019. We reprocessed the echocardiograms using a vendor neutral software to obtain the two-dimensional LV GLS. Results: Among the 148 participants, 59% were female. Compared with females, males had lower BMIs, a higher prevalence of prior myocardial infarction or revascularization, and a greater severity of nocturnal airway obstruction and hypoxia. Males also had a greater proportion with abnormal LV GLS (≥ -17). See Table. The prevalence of abnormal MFR (< 2.0) was higher among participants with abnormal LV GLS ( P = 0.031). This association was persistent among males but was lost among females (see Figure ). In age and sex adjusted logistic regression persons with abnormal LV GLS had 2X the odds of abnormal MFR (OR 2.3; 95% CI: 1.02 - 5.03). Among males, this association was significant (OR 4.8; 95%CI:1.5 - 13.7). No association observed among females. Formal interaction analyses did not meet statistical significance ( P int = 0.106). Conclusions: In this patient population with SDB, there was a significant association between LV GLS and abnormal MFR. The sex differences in the relationship may be due to differences in the severity of OSA and prevalence of ischemic heart disease. Future studies should clarify these relationships and elucidate the drivers of the sex disparities observed in these findings.

Abstract 15635: Sex Differences in the Effect of Nocturnal Hypoxia on Right Ventricular Myocardial Blood Flow

Introduction: Nocturnal hypoxia is common in patients with obstructive sleep apnea (OSA). However, it is unclear how nocturnal hypoxia affects the structure and function of the right ventricle (RV), and if there are sex differences in the impact of nocturnal hypoxia on RV dysfunction. We examined the sex-specific relationship between nocturnal hypoxia, as measured as T90% (time asleep with <90% oxygen saturation), and RV myocardial blood flow (MBF) and myocardial flow reserve (MFR). Methods: RV MBF and MFR were examined for 78 patients who had a cardiac PET stress test and a sleep test between 2015 to 2019. MBF was analyzed using FlowQuant software (Ottawa, Canada). MFR was defined as the ratio of stress to rest MBF. We categorized reduced RV MFR as < 2.3 (corresponding to the median value) and nocturnal hypoxia as T90 ≥ 8%. Results: The mean (± SD) age was 63 ± 10 years. Most patients (83%) were obese (BMI ≥ 30kg/m3). Fifty-one patients (63%) were female. Although not statistically significant, the median RV MFR was higher among females (2.4 vs. 2.2, p = 0.158). RV MFR was higher among those without nocturnal hypoxia compared to those with nocturnal hypoxia (2.4 vs. 2.0, p = 0.023). Among females, the median RV MFR was higher among those without significant nocturnal hypoxia (2.5 vs. 1.8, p = 0.004), while males showed no relationship (2.2 vs. 2.2, p = 0.696; see table for details). In age and BMI adjusted logistic regression analysis, patients with nocturnal hypoxia were 3X as likely to have reduced RV MFR (OR = 3.2, 95% CI: 1.1 - 9.3) and there was a significant statistical interaction by sex (p = 0.046). Conclusions: These findings suggest that nocturnal hypoxia is associated with a reduction in RV MFR, more prominently among females. Future studies should focus on elucidating the pathophysiologic implications of our findings and understanding the biologic processes that account for the sex differences observed.

Abstract 17436: A Diagnostic Copycat: Culture Negative Endocarditis of A Bioprosthetic Valve Presenting as ANCA Vasculitis

A 59-year-old female with a history of bicuspid aortic valve (AV) complicated by aortic stenosis and ascending aortic aneurysm s/p bioprosthetic AV and ascending aorta replacement presented with a 6-month history of weight loss, fatigue, and lower extremity rash. Initial laboratory workup identified anemia, leukopenia, and acute kidney injury with proteinuria and microscopic hematuria. Further workup included negative blood cultures, elevated inflammatory markers, elevated rheumatoid factor, hypocomplimentemia, and ANCA positivity (PR3 Ab positive). Biopsy of her palpable purpuric rash demonstrated vascular immune deposition pattern consistent with leukocytoclastic vasculitis. Renal biopsy revealed focal and crescentic glomerulonephritis with immune complex deposition. CT abdomen noted mesenteric lymphadenopathy with fluid surrounding the thoracic aortic graft. Surface echocardiogram showed bioprosthetic AV replacement with diffuse cusp thickening without stenosis or regurgitation. At this point, a multidisciplinary team offered a broad differential diagnosis of inflammatory vasculitis versus culture-negative endocarditis with plan for further testing. Follow-up whole-body and cardiac PET scan identified FDG-avid abnormalities involving the aortic graft and AV with hypermetabolic soft tissue thickening surrounding the aortic root. Transesophageal echocardiogram confirmed AV thickening with a 1 cm mobile echodensity. Additional serologic testing identified positive Bartonella henselae IgG (1:8192) and IgM (>1:20) titers. The final diagnosis was B. henselae prosthetic AV endocarditis and ascending aortic graft infection. She underwent repeat AV and ascending aortic graft replacement, with graft material positive for B. henselae PCR and was treated with a course of doxycycline and rifampin. B. henselae is a fastidious gram-negative bacterium that can cause culture negative endocarditis but is very rarely associated with aortic graft infection. This case highlights (1) a rare example of B. henselae aortic graft infection, (2) the difficulty in differentiating B. henselae endocarditis from inflammatory vasculitis, and (3) the importance of engaging multidisciplinary teams to solve difficult diagnostic cases.

Cytomegalovirus infection is associated with impaired myocardial flow reserve after heart transplantation

BackgroundCardiac allograft vasculopathy (CAV) limits long-term survival after heart transplantation (HT). This study evaluates the relationship between clinically significant CMV infection (CS-CMVi) and CAV using cardiac positron emission tomography (PET). MethodsWe retrospectively evaluated HT patients from 2005-2019 who underwent cardiac PET for CAV evaluation. Multivariable linear and logistic regression models were used to evaluate the association between CS-CMVi and myocardial flow reserve (MFR). Kaplan-Meier and Cox regression analyses were used to assess the relationship between CS-CMV, MFR, and clinical outcomes. ResultsThirty-two (31.1%) of 103 HT patients developed CS-CMVi at a median 9 months after HT. Patients with CS-CMVi had a significantly lower MFR at Year 1 and 3, driven by reduction in stress myocardial blood flow. Patients with CS-CMVi had a faster rate of decline in MFR compared to those without infection (-0.10 vs -0.06 per year, P <0.001). CS-CMVi was an independent predictor of abnormal MFR (<2.0) (OR: 3.8, 95% CI: 1.4-10.7, P = 0.001) and a lower MFR (β = -0.39, 95% CI: -0.63 to -0.16, P = 0.001) at Year 3. In adjusted survival analyses, both abnormal MFR (log-rank P <0.001; HR: 5.7, 95% CI: 4.2-7.2) and CS-CMVi (log-rank P = 0.028; HR: 3.3, 95% CI: 1.8-4.8) were significant predictors of the primary outcome of all-cause mortality, retransplantation, heart failure hospitalization, and acute coronary syndrome. ConclusionCS-CMVi is an independent predictor of reduced MFR following HT. These findings suggest that CMV infection is an important risk factor in the development and progression of CAV.

Detection of sympathetic denervation defects in Fabry disease by hybrid [11C]meta-hydroxyephedrine positron emission tomography and cardiac magnetic resonance

BackgroundMyocardial glycosphingolipid accumulation in patients with Fabry disease (FD) causes biochemical and structural changes. This study aimed to investigate sympathetic innervation in FD using hybrid cardiac positron emission tomography (PET)/magnetic resonance imaging (MRI). Methods and resultsPatients with different stages of Fabry disease were prospectively enrolled to undergo routine CMR at 1.5T, followed by 3T hybrid cardiac PET/MRI with [11C]meta-hydroxyephedrine ([11C]mHED). Fourteen patients with either no evidence of cardiac involvement (n = 5), evidence of left ventricular hypertrophy (LVH) (n = 3), or evidence of LVH and fibrosis via late gadolinium enhancement (LGE) (n = 6) were analyzed. Compared to patients without LVH, patients with LVH or LVH and LGE had lower median T1 relaxation times (ms) at 1.5 T (1007 vs. 889 vs. 941 ms, p = 0.003) and 3T (1290 vs. 1172 vs. 1184 p = .014). Myocardial denervation ([11C]mHED retention < 7%·min) was prevalent only in patients with fibrosis, where a total of 16 denervated segments was found in two patients. The respective area of denervation exceeded the area of LGE in both patients (24% vs. 36% and 4% vs. 32%). However, sympathetic innervation defects ([11C]mHED retention ≤ 9%·min) occurred in all study groups. Furthermore, a reduced sympathetic innervation correlated with an increased left ventricular mass (p = .034, rs = − 0.57) and a reduced global longitudinal strain (GLS) (p = 0.023, rs = − 0.6). ConclusionHybrid cardiac PET/MR with [11C]mHED revealed sympathetic innervation defects, accompanied by impaired GLS, in early stages of Fabry disease. However, denervation is only present in patients with advanced stages of FD showing fibrosis on CMR.

Coronary vasculopathy due to moyamoya disease

Moyamoya disease is a rare disorder associated with progressive intracranial arterial stenosis with fragile, small collateralization that gives an angiographic appearance of a puff of smoker or, in Japanese, “moya-moya”. We report a case of coronary artery ostial occlusive disease as an extracranial manifestation of Moyamoya. In the case, we demonstrate that thigh risk features of cardiac positron emission tomography (PET) that ultimately lead to the diagnosis of coronary artery occlusion.

Novel Functional Radiomics for Prediction of Cardiac PET Avidity in Lung Cancer Radiotherapy

Traditional methods of evaluating cardiotoxicity focus solely on radiation doses to the heart and do not incorporate functional imaging information. Functional imaging has great potential to improve the ability to provide early prediction for cardiotoxicity for lung cancer patients undergoing radiotherapy. FDG-based PET/CT imaging is routinely obtained as part of standard staging work up for lung cancer patients. Although FDG PET/CT scans are typically used to evaluate the tumor, imaging guidelines note that FDG PET/CT scans are an FDA-approved method to image for cardiac inflammation, and studies have noted that the PET cardiac signal can be predictive of clinical outcomes. The purpose of this work was to develop a radiomics model to predict clinical cardiac assessment of standard of care FDG PET/CT scans. The study included 100 consecutive lung cancer patients treated with radiotherapy who underwent standard pre-treatment FDG-PET/CT staging scans. A clinician reviewed the PET/CT scans per clinical cardiac assessment guidelines and classified the cardiac uptake as: 0 = uniform diffuse, 1 = absent, 2 = heterogeneous, with event rates of 20%, 44%, and 35%, respectively. The heart was delineated and 200 novel functional radiomics features were selected to classify cardiac FDG uptake patterns. We divided the data into an 80% training set and a 20% test set to train and evaluate the classification models. Feature reduction was carried out using the Wilcoxon test (with Bonferroni adjusted p<0.05), hierarchical clustering, and Recursive Feature Elimination. Two automatic machine learning (AutoML) frameworks were used to determine classification models: a Random Forest Classifier (Tree-based Pipeline Optimization Tool, TPOT) and Linear Discriminant Analysis (AutoSklearn). 10-fold cross validation was carried out for training and the accuracy of the ability of the models to predict for clinical cardiac assessment is reported. Fifty-one independent radiomics features were reduced to 3 clinically pertinent features (PET 2D Skewness, PET Grey Level Co-occurrence Matrix Correlation, and PET Median) using feature reduction techniques. The model selected by TPOT showed 89.8% predictive accuracy in the cross validation of the training set and 85% predictive accuracy on the test set. The model selected by AutoSklearn showed 89.7% predictive accuracy in the cross validation of the training set and 80% predictive accuracy on the test set. The novelty of this work is that it is the first study to develop and evaluate functional cardiac radiomic features from standard of care FDG PET/CT scans with the data showing good predictive accuracy with clinical imaging evaluation. If validated, the current work provides automated methods to provide functional cardiac information using standard of care imaging that can be used as an imaging biomarker for early clinical toxicity prediction for lung cancer patients.

Contemporary Features and Management of Endocarditis.

Infective endocarditis is a rare but devastating disease. Morbidity and mortality rates have failed to improve despite new technological advances. The disease has evolved over time with new significant populations at risk-most notably those with prosthetic valves or implantable cardiovascular devices. These devices pose new challenges for achieving a timely and accurate diagnosis of infection. While the modified Duke criteria is accepted as the gold standard for diagnosing native valve endocarditis, it has been shown to have significantly inferior sensitivity when it comes to identifying infections related to right-heart endocarditis, prosthetic valves, and indwelling cardiac devices. Additionally, prosthetic valves and cardiovascular implantable electronic devices can exhibit shadowing and artifact, rendering transthoracic echocardiography and transesophageal echocardiography results inconclusive or even normal. Having a keen awareness of the varying clinical presentations, as well as emerging valvular imaging modalities such as F-fluorodeoxyglucose cardiac positron-emission tomography plus computed tomography, promises to improve the evaluation and diagnosis of infective endocarditis. However, indications for appropriate use of these studies and guidance on modern clinical management are still needed.

Comparison of cardiac magnetic resonance imaging and fluorodeoxyglucose positron emission tomography in the assessment of myocardial viability: meta-analysis and systematic review.

Contrast-enhanced cardiac magnetic resonance (Ce-CMR) and Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) are frequently utilized in clinical practice to assess myocardial viability. However, studies evaluating direct comparison between Ce-CMR and FDG-PET have a smaller sample size, and no clear distinction between the two imaging modalities has been defined. To address this gap, we conducted a meta-analysis of studies comparing Ce-CMR and FDG-PET for the assessment of myocardial viability. We searched PubMed, EMBASE, Scopus, and Web of Science databases from their inception to 4/20/2022 with search terms "viability" AND "heart diseases" AND "cardiac magnetic resonance imaging" AND "positron-emission tomography." We extracted patient characteristics, segment level viability assessment according to Ce-CMR and FDG-PET, and change in regional wall motion abnormalities (RWMA) at follow-up. We included four studies in the meta-analysis which provided viability assessment with Ce-CMR and FDG-PET in all patients and change in RWMA at follow-up. There were 82 patients among the four included studies, and 585 segments were compared for viability assessment. There were 59 (72%) males, and mean age was 65 years. The sensitivity (95% confidence interval-CI) and specificity (CI) of Ce-CMR for predicting myocardial recovery were 0.88 (0.66-0.96) and 0.64 (0.49-0.77), respectively. The sensitivity (CI) and specificity (CI) of FDG-PET for predicting myocardial recovery were 0.91 (0.63-0.99) and 0.67 (0.49-0.81), respectively. FDG-PET and Ce-CMR have comparable diagnostic parameters in myocardial viability assessment and are consistent with prior research.

Body Composition, Coronary Microvascular Dysfunction, and Future Risk of Cardiovascular Events Including Heart Failure

BackgroundBody mass index (BMI) is a controversial marker of cardiovascular prognosis, especially in women. Coronary microvascular dysfunction (CMD) is prevalent in obese patients and a better discriminator of risk than BMI, but its association with body composition is unknown. ObjectivesThe authors used a deep learning model for body composition analysis to investigate the relationship between CMD, skeletal muscle (SM), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT), and their contribution to adverse outcomes in patients referred for evaluation of coronary artery disease. MethodsConsecutive patients (n = 400) with normal perfusion and preserved left ventricular ejection fraction on cardiac stress positron emission tomography were followed (median, 6.0 years) for major adverse events, including death and hospitalization for myocardial infarction or heart failure. Coronary flow reserve (CFR) was quantified as stress/rest myocardial blood flow from positron emission tomography. SM, SAT, and VAT cross-sectional areas were extracted from abdominal computed tomography at the third lumbar vertebra using a validated automated algorithm. ResultsMedian age was 63, 71% were female, 50% non-White, and 50% obese. Compared with the nonobese, patients with obesity (BMI: 30.0-68.4 kg/m2) had higher SAT, VAT, and SM, and lower CFR (all P < 0.001). In adjusted analyses, decreased SM but not increased SAT or VAT was significantly associated with CMD (CFR <2; OR: 1.38; 95% CI: 1.08-1.75 per –10 cm2/m2 SM index; P < 0.01). Both lower CFR and SM, but not higher SAT or VAT, were independently associated with adverse events (HR: 1.83; 95% CI: 1.25-2.68 per –1 U CFR and HR: 1.53; 95% CI: 1.20-1.96 per −10 cm2/m2 SM index, respectively; P < 0.002 for both), especially heart failure hospitalization (HR: 2.36; 95% CI: 1.31-4.24 per –1 U CFR and HR: 1.87; 95% CI: 1.30-2.69 per –10 cm2/m2 SM index; P < 0.004 for both). There was a significant interaction between CFR and SM (adjusted P = 0.026), such that patients with CMD and sarcopenia demonstrated the highest rate of adverse events, especially among young, female, and obese patients (all P < 0.005). ConclusionsIn a predominantly female cohort of patients without flow-limiting coronary artery disease, deficient muscularity, not excess adiposity, was independently associated with CMD and future adverse outcomes, especially heart failure. In patients with suspected ischemia and no obstructive coronary artery disease, characterization of lean body mass and coronary microvascular function may help to distinguish obese phenotypes at risk for cardiovascular events.

Assessment of resting myocardial blood flow in regions of known transmural scar to confirm accuracy and precision of 3D cardiac positron emission tomography

BackgroundComposite invasive and non-invasive data consistently demonstrate that resting myocardial blood flow (rMBF) in regions of known transmural myocardial scar (TMS) converge on a value of ~ 0.30 mL/min/g or lower. This value has been confirmed using the 3 most common myocardial perfusion agents (13N, 15O-H2O and 82Rb) incorporating various kinetic models on older 2D positron emission tomography (PET) systems. Thus, rMBF in regions of TMS can serve as a reference “truth” to evaluate low-end accuracy of various PET systems and software packages (SWPs). Using 82Rb on a contemporary 3D-PET-CT system, we sought to determine whether currently available SWP can accurately and precisely measure rMBF in regions of known TMS.ResultsMedian rMBF (in mL/min/g) and COV in regions of TMS were 0.71 [IQR 0.52–1.02] and 0.16 with 4DM; 0.41 [0.34–0.54] and 0.10 with 4DM-FVD; 0.66 [0.51–0.85] and 0.11 with Cedars; 0.51 [0.43–0.61] and 0.08 with Emory-Votaw; 0.37 [0.30–0.42], 0.07 with Emory-Ottawa, and 0.26 [0.23–0.32], COV 0.07 with HeartSee.ConclusionsSWPs varied widely in low end accuracy based on measurement of rMBF in regions of known TMS. 3D PET using 82Rb and HeartSee software accurately (0.26 mL/min/g, consistent with established values) and precisely (COV = 0.07) quantified rMBF in regions of TMS. The Emory-Ottawa software yielded the next-best accuracy (0.37 mL/min/g), though rMBF was higher than established gold-standard values in ~ 5% of the resting scans. 4DM, 4DM-FDV, Cedars and Emory-Votaw SWP consistently resulted values higher than the established gold standard (0.71, 0.41, 0.66, 0.51 mL/min/g, respectively), with higher interscan variability (0.16, 0.11, 0.11, and 0.09, respectively).Trial registration: clinicaltrial.gov, NCT05286593, Registered December 28, 2021, https://clinicaltrials.gov/ct2/show/NCT05286593.

Quantitative myocardial perfusion should be interpreted in the light of sex and comorbidities in patients with suspected chronic coronary syndrome: A cardiac positron emission tomography study.

Diagnosis and treatment of patients with suspected chronic coronary syndrome (CCS) currently relies on the degree of coronary artery stenosis and its significance for myocardial perfusion. However, myocardial perfusion can be affected by factors other than coronary stenosis. The aim of this study was to investigate to what extent sex, age, diabetes, hypertension and smoking affect quantitative myocardial perfusion, beyond the degree of coronary artery stenosis, in patients with suspected or established CCS. Eighty-six patients [median age 69 (range 46-86)years, 24 females]planned for elective coronary angiography due to suspected or established CCS were included. All patients underwent cardiac 13 N-NH3 positron emission tomography to quantify myocardial perfusion at rest and stress. Lowest myocardial perfusion (perfusionmin ) at stress and rest and lowest myocardial perfusion reserve (MPRmin ) for all vessel territories was used as dependent variables in a linear mixed model. Independent variables were vessel territory, degree of coronary artery stenosis (as a continuous variable of 0%-100% stenosis), sex, age, diabetes, hypertension and smoking habits. Degree of coronary artery stenosis (p < 0.001), male sex (1.8 ± 0.6 vs. 2.3 ± 0.6 mL/min/g, p < 0.001), increasing age (p = 0.025), diabetes (1.6 ± 0.5 vs. 2.0 ± 0.6 mL/min/g, p = 0.023) and smoking (1.9 ± 0.6 vs. 2.1 ± 0.6 mL/min/g, p = 0.052) were independently associated with myocardial perfusionmin at stress. Degree of coronary artery stenosis (p < 0.001), age (p = 0.040), diabetes (1.8 ± 0.6 vs. 2.3 ± 0.7, p = 0.046) and hypertension (2.2 ± 0.7 vs. 2.5 ± 0.6, p = 0.033) were independently associated with MPRmin . Sex, increasing age, diabetes, hypertension and smoking affect myocardial perfusion independent of coronary artery stenosis in patients with suspected or established CCS. Thus, these factors need to be considered when assessing the significance of reduced quantitative myocardial perfusion of patients with suspected or established CCS.

Detection and correction of patient motion in dynamic 15O-water PET MPI

BackgroundPatient motion constitutes a limitation to 15O-water cardiac PET imaging. We examined the ability of image readers to detect and correct patient motion using simulated motion data and clinical patient scans.MethodsSimulated data consisting of 16 motions applied to 10 motion-free scans were motion corrected using two approaches, pre-analysis and post-analysis for motion identification. Both approaches employed a manual frame-by-frame correction method. In addition, a clinical cohort was analyzed for assessment of prevalence and effect of motion and motion correction.ResultsMotion correction was performed on 94% (pre-analysis) and 64% (post-analysis) of the scans. Large motion artifacts were corrected in 91% (pre-analysis) and 74% (post-analysis) of scans. Artifacts in MBF were reduced in 56% (pre-analysis) and 58% (post-analysis) of the scans. The prevalence of motion in the clinical patient cohort (n = 762) was 10%. Motion correction altered exam interpretation in only 10 (1.3%) clinical patient exams.ConclusionFrame-by-frame motion correction after visual inspection is useful in reducing motion artifacts in cardiac 15O-water PET. Reviewing the initial results (parametric images and polar maps) as part of the motion correction process, reduced erroneous corrections in motion-free scans. In a large clinical cohort, the impact of motion correction was limited to few patients.

Real-Life Utilization of Criteria Guidelines for Diagnosis of Cardiac Sarcoidosis (CS).

Despite the increasing recognition of cardiac involvement in systemic sarcoidosis, the diagnosis of cardiac sarcoidosis (CS) remains challenging. Our aim is to present a comprehensive, retrospective case series of CS patients, focusing on the current diagnostic guidelines and management of this life-threatening condition. In our case series, patient data were collected retrospectively, including hospital admission records and rheumatology and cardiology clinic visit notes, detailing demographic, clinical, laboratory, pathology, and imaging studies, as well as cardiac devices and prescribed medications. Cases were divided into definite and probable CS based on the 2014 Heart Rhythm Society guidelines as well as presumed CS based on imaging criteria and clinical findings. Overall, 19 CS patients were included, 17 of whom were diagnosed with probable or presumed CS based on cardiac magnetic resonance imaging (CMR) and/or cardiac positron emission tomography using 18F-Fluorodeoxyglucose (PET-FDG) without supporting endomyocardial biopsy (EMB). The majority of CS patients were male (53%), with a mean age of 52.9 ± 11.8, with CS being the initial manifestation of sarcoidosis in 63% of cases. Most patients presented with high-grade AVB (63%), followed by heart failure (42%) and ventricular tachyarrhythmia (VT) (26%). This case series highlights the significance of utilizing updated diagnostic criteria relying on CMR and PET-FDG given that cardiac involvement can be the initial manifestation of systemic sarcoidosis, requiring prompt diagnosis and treatment to prevent morbidity and mortality.

Optimal left ventricular ejection fraction in risk stratification of patients with cardiac sarcoidosis.

Identifying patients with cardiac sarcoidosis (CS) who are at an increased risk of sudden cardiac death (SCD) poses a clinical challenge. We sought to identify the optimal cutoff for left ventricular ejection fraction (LVEF) in predicting ventricular arrhythmia (VA) and all-cause mortality and to identify clinical and imaging risk factors in patients with known CS. This retrospective cohort included 273 patients with well-established CS. The primary endpoint was a composite of VA and all-cause mortality. A modified receiver operating curve analysis was utilized to identify the optimal cutoff for LVEF in predicting the primary composite endpoint. Cox proportional hazard regression analysis was used to identify independent risk factors of the outcomes. At median follow-up of 7.9 years, the rate of the primary endpoint was 38% (83 VAs and 32 all-cause deaths). The 5-year overall survival rate was 97%. The optimal cutoff LVEF for the primary composite endpoint was 42% in the entire cohort and in subjects without a history of VA. Younger age, history of VA, lower LVEF, and any presence of scar by cardiac magnetic resonance (CMR) imaging and/or positron emission tomography (PET) were found to be independent risk factors for the primary endpoint and for VA, whereas lower LVEF, baseline NT-proBNP, and any presence of scar were independent risk factor of all-cause mortality. Among patients with CS, a mild reduction in LVEF of 42% was identified as the optimal cutoff for predicting VA and all-cause mortality. Prior VA and scar by CMR or PET are strong risk factors for future VA and all-cause mortality.

Does financial hardship associate with abnormal quantitative myocardial perfusion and major adverse cardiovascular event?

BackgroundData on impact of financial hardship on coronary artery disease (CAD) remain incomplete. MethodsConsecutive subjects referred for clinical rest/stress cardiac positron emission tomography (PET) were enrolled. Financial hardship is defined as patients’ inability to pay for their out-of-pocket expense for cardiac PET. Abnormal cardiac PET is defined as at least moderate relative perfusion defects at stress involving > 10% of the left ventricle or global coronary flow reserve ≤ 2.0. Patients were followed for major adverse cardiovascular event (MACE) comprised of all-cause mortality, non-fatal myocardial infarction, and late coronary revascularization. ResultsWe analyzed a total of 4173 patients with mean age 65.6 ± 11.3 years, 72.2% men, and 93.6% reported as having medical insurance. Of these, 504 (12.1%) patients had financial hardship. On multivariable analysis, financial hardship associated with abnormal cardiac PET (odds ratio 1.377, p = 0.004) and MACE (hazard ratio 1.432, p = 0.010) and its association with MACE was mostly through direct effect with small proportion mediated by abnormal cardiac PET or known CAD. ConclusionAmong patients referred for cardiac rest/stress PET, financial hardship independently associates with myocardial perfusion abnormalities and MACE; however, its effect on MACE is largely not mediated by abnormal myocardial perfusion or known CAD suggesting distinct impact of financial hardship beyond traditional risk factors and CAD that deserves attention and intervention to effectively reduced adverse outcomes. Having medical insurance does not consistently protect from financial hardship and a more preventive-oriented restructuring may provide better outcomes at lower cost.