Myocardial Uptake Research Articles

Prevalence of Incidental Findings Suspicious for Transthyretin Cardiac Amyloidosis among Patients Undergoing Bone Scintigraphy: A Systematic Review and a Meta-Analysis.

The myocardial uptake of bone-seeking tracers suspicious for transthyretin cardiac amyloidosis (ATTR-CA) can be incidentally detected in patients undergoing bone scintigraphy for noncardiac reasons. We conducted a systematic review and meta-analysis to assess the prevalence of these scintigraphic findings. A comprehensive literature search was performed using two bibliographic databases (PubMed/MEDLINE and Cochrane Library), searching for articles related to the review question. Eligible articles were selected, and relevant data were extracted by two authors. The pooled prevalence of incidental findings suspicious for ATTR-CA among patients undergoing bone scintigraphy was calculated on a per-patient-based analysis using a random-effects model. The pooled measure was provided with 95% confidence interval (95% CI) values. Among 219 records, 11 articles were selected for the systematic review and 10 for the meta-analysis. The pooled prevalence of incidental findings suspicious for ATTR-CA was 1.1% (95% CI: 0.7-1.4%) with heterogeneity due to the characteristics of the included studies, patients, and index tests. These findings are more prevalent in older men. The prevalence of incidental findings of ATTR-CA among patients undergoing bone scintigraphy is low but not negligible. Nuclear medicine physicians should suggest, in the scintigraphic report, further clinical investigations when these findings are detected. Prospective studies are warranted.

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

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. 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). 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). 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.

Autonomic dysfunction in dementia with Lewy bodies: Focusing on cardiovascular and respiratory dysfunction.

Dementia with Lewy bodies (DLB) is the second most common cause of dementia after Alzheimer's disease. The disease is characterized by many Lewy bodies appearing in the patient's cerebrum. DLB frequently presents with a variety of autonomic symptoms from the early or prodromal stages of the disease, and these are listed as supportive features in the diagnostic criteria. As several useful assessment methods for evaluating autonomic function in DLB have been reported, this review will focus on cardiovascular and respiratory dysfunction and its assessments. Cardiovascular disorders, such as orthostatic hypotension and abnormal heart rate variability, have been reported in DLB patients. Decreased myocardial uptake by metaiodobenzylguanidine myocardial scintigraphy has been added as an indicative biomarker for DLB in the 2017 revision of the diagnostic criteria. We have reported reduced ventilatory response to hypercapnia, abnormal respiratory rhythm, and high frequency of sleep-disordered breathing as abnormalities of the respiratory regulatory system associated with DLB. Since autonomic dysfunction is highly prevalent in DLB from the early or prodromal phase of the disease and is associated with reduced activities of daily living and quality of life, the evaluation of autonomic dysfunction is also useful in the differential diagnosis of DLB from Alzheimer's disease. There are fewer studies on the respiratory regulatory system than on the cardiovascular system, thus further research is needed to explore its role in DLB.

Reduction in 99mTc-DPD myocardial uptake with therapy of ATTR cardiomyopathy

Aims: Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv). We aimed to determine the impact of RNAi therapeutics on myocardial amyloid load using quantitative single photon emission computed tomography/computed tomography (SPECT/CT) imaging in patients with ATTRv-related cardiomyopathy (ATTRv-CM). We furthermore compared them with wild-type ATTR-CM (ATTRwt-CM) patients treated with tafamidis. Methods and results: ATTRv-CM patients underwent [99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy and quantitative SPECT/CT imaging before and after 12 months (IQR: 11.0–12.0) of treatment with RNAi therapeutics (patisiran: n = 5, inotersen: n = 4). RNAi treatment significantly reduced quantitative myocardial uptake as measured by standardised uptake value (SUV) retention index (baseline: 5.09 g/mL vs. follow-up: 3.19 g/mL, p = .028) in ATTRv-CM patients without significant improvement in cardiac function. Tafamidis treatment resulted in a significant reduction in SUV retention index (4.96 g/mL vs. 3.27 g/mL, p < .001) in ATTRwt-CM patients (historical control cohort: n = 40) at follow-up [9.0 months (IQR: 7.0–10.0)] without beneficial impact on cardiac function. Conclusions: RNAi therapeutics significantly reduce quantitative myocardial uptake in ATTRv-CM patients, comparable to tafamidis treatment in ATTRwt-CM patients, without impact on cardiac function. Serial 99mTc-DPD SPECT/CT imaging may be a valuable tool to quantify and monitor response to disease-specific therapies in both ATTRv-CM and ATTRwt-CM.

Clinical Response to Tumor Necrosis Factor-α Inhibitor Therapy in the Management of Cardiac Sarcoidosis

Evidence that tumor necrosis factor-α (TNF-α) inhibitors may benefit patients with cardiac sarcoidosis (CS) is limited to small case series and both imaging and clinical outcomes in this population are not well known. This study aimed to evaluate the disease course of patients with CS treated with either infliximab or adalimumab therapy based on serial 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging and clinical outcomes. An institutional CS research database was queried for patients treated with TNF-α inhibitors between 2016 and 2021. Outcomes included (1) change in mean prednisone dose, (2) FDG-PET improvement, and (3) unplanned hospitalizations, advanced heart failure therapies, or death. Our query yielded 31 patients with CS. A total of 13 patients were on infliximab, 15 patients were on adalimumab, and 3 patients were on adalimumab before transitioning to infliximab. Mean prednisone dose decreased between FDG-PET immediately preceding TNF-α and second after TNF-α FDG-PET (18.6±15.7mg to 7.7±12.4mg, p=0.018). A significant decrease was seen in the mean number of segments demonstrating FDG uptake between most recent pre-TNF-α and first after TNF-α inhibitor FDG-PET (mean segments=4.2 vs 3.1, p=0.048). Between earliest pre-TNF-α and first after TNF-α FDG-PET there was a numerical decrease in average myocardial maximum standard uptake values (SUVmax) (4.4 vs 3.1, p=0.18), and the ratio of SUVmax myocardium:SUVmax blood pool (1.9 vs 1.5, p=0.26). Within 36months of initiating TNF-α inhibitor, 4 patients (13%) experienced unplanned cardiovascular hospitalization (median time to hospitalization=12.1months). In conclusion, in patients with CS, TNF-α inhibitor therapy is associated with decreased glucocorticoid use, numerical decrease in cardiac FDG uptake, and minimal cardiac morbidity.

Abstract P3153: Human Bone Mesenchymal Stem Cell Lentiviral Transduction For The Production Of Extracellular Vesicles Targeted To The Heart Limits Cell Line Expansion

Objectives: Human bone mesenchymal stem cell derived-extracellular vesicles (HBMSC-EV) have been found to have regenerative and anti-inflammatory effects in heart disease, but one of the main obstacles of this treatment modality is the lack of practical delivery to the heart. To make intravenous delivery possible, this study sought to create a human bone mesenchymal stem cell (HBMSC) that secretes HBMSC-EV which will avoid macrophage uptake and home to the heart through lentiviral genetic modification. Methods: The following HBMSC extracellular genetic modifications were selected: CD-47, an anti-phagocytic marker; cardiac targeting peptide (CTP, sequence APWHLSSQYSRT) and ischemic myocardium targeting peptide (IMTP, sequence CSTSMLKAC), peptides both found to have selective cardiac and ischemic myocardium uptake, respectively, through previous biopanning research. Through a 3 rd generation lentiviral system and subsequent antibiotic selection process, wild-type HBMSC were altered to carry these modifications. Results: Three HMBSC lines were created: 1) CD-47 only, 2) CD-47 and CTP anchored to the outer cell membrane by Lamp-2b, and 3) CD-47 and IMTP anchored by Lamp-2b. Preliminary findings show hindered cell proliferation and adherence - cell doubling time was significantly slowed by passage 6 (versus passage 10 in wild-type HBMSC). Also, the genetically modified HBMSC required a 1:2 subculture ratio (versus 1:3-4 in wild-type HBMSC). Conclusions: These genetically-modified HBMSC, engineered with a goal to be better suited for HBMSC-EV production in the treatment of cardiac disease, have significant limitations in cell proliferation and expansion, which will be a significant obstacle to the production of a meaningful quantity of HBMSC-EV. Ongoing studies are being carried out to characterize changes in HBMSC differentiation and in the cell-matrix.

Extensive cardiac FDG uptake in a patient with AL amyloidosis

Cardiac AL amyloidosis is a medical emergency causing rapid deterioration of cardiac function; however, it remains to be a diagnostic challenge especially when presenting with unusual symptoms and clinical findings. We present case of a 44-year-old patient with typical angina, persistently elevated troponin and normal epicardial coronary arteries. He was initially treated for myocarditis due to chest pain with troponin rise. However, CMR finding of subendocardial enhancement, increased native T1 values as well as extensive diffuse FDG uptake on PET-CT also suggested inflammatory cardiac conditions. Rapid decline in LV function and clinical deterioration led to further investigations including serum free light chains and bone marrow biopsy which confirmed systemic AL amyloidosis. Although the pathophysiology of unusual FDG PET-CT findings remains unknown, marked myocardial FDG uptake might have been caused by various features that were associated with AL amyloidosis including myocardial cell toxicity/inflammation or microvascular dysfunction. Awareness of these features specific to AL amyloidosis among physicians and description of associated cardiac FDG uptake findings has a potential to aid early diagnosis.

Cardiac DPD-uptake time dependency in ATTR patients verified by quantitative SPECT/CT and semiquantitative planar parameters

BackgroundBone scintigraphy plays an important role in the diagnosis of cardiac Transthyretin-Related Amyloidosis (ATTR). The mechanism of myocardial tracer accumulation and its dependence over time are not fully understood. Recently, a scintigraphic quantification of the cardiac amyloid deposition has been discussed. Nevertheless, little is known regarding the right time of quantitative imaging. MethodsThe geometrical mean of decay corrected total counts over the heart and the heart/whole-body ratio (H/WB) were evaluated in 23 patients undergoing DPD-bone scan with planar whole-body images 1 and 3 hours post injection (p.i.). Myocardial standard uptake values (SUV)peak were assessed in another 15 patients with quantitative SPECT/CT imaging 1 hours and 3 hours p.i.. ResultsTotal counts over the heart (1 hours p.i.: 81,676 cts, range 69,887 to 93,091 cts and 3 hours p.i.: 64,819 cts, range 52,048 to 86,123 cts, P = .0005) and H/WB ratio (1 hours p.i.:0.076 ± 0.020 and 3 hours p.i. 0.070 ± 0.022; P = .0003) were significantly increased 1 hours p.i.. Furthermore median myocardial SUVpeak (1 hours p.i.:12.2, range 9.6 to 18.9 and 3 hours p.i.: 9.6, range 8.2 to 15.0, P = 0.0012) was also significantly higher after 1 hours p.i. compared to 3 hours p.i.. ConclusionCardiac DPD activity and myocardial SUVpeak are time-dependent, which should be considered when using quantitative bone scintigraphy in ATTR patients.

Prednisone vs methotrexate in treatment naïve cardiac sarcoidosis

BackgroundSide effects limit the long-term use of glucocorticoids in cardiac sarcoidosis (CS), and methotrexate has gained attention as steroid sparing agent although the supporting evidence is poor. This study compared prednisone monotherapy, methotrexate monotherapy or a combination of both, in the reduction of myocardial Fluorine-18 fluorodeoxyglucose (FDG) uptake and clinical stabilization of CS patients. Methods and resultsIn this retrospective cohort study, 61 newly diagnosed and treatment naïve CS patients commenced treatment with prednisone (N = 21), methotrexate (N = 30) or prednisone and methotrexate (N = 10) between January 2010 and December 2017. Primary outcome was metabolic response on FDG PET/CT and secondary outcomes were treatment patterns, major adverse cardiovascular events, left ventricular ejection fraction, biomarkers and side effects. At a median treatment duration of 6.2 [5.7-7.2] months, 71.4% of patients were FDG PET/CT responders, and the overall myocardial maximum standardized uptake value decreased from 6.9 [5.0-10.1] to 3.4 [2.1-4.7] (P < 0.001), with no significant differences between treatment groups. During 24 months of follow-up, 7 patients (33.3%; prednisone), 6 patients (20.0%; methotrexate) and 1 patient (10.0%; combination group) experienced at least one major adverse cardiovascular event (P = 0.292). Left ventricular ejection fraction was preserved in all treatment groups. ConclusionsSignificant suppression of cardiac FDG uptake occurred in CS patients after 6 months of prednisone, methotrexate or combination therapy. There were no significant differences in clinical outcomes during follow-up. These results warrant further investigation of methotrexate treatment in CS patients.

Complete resolution of focal-on-diffuse myocardial activity pattern on FDG PET-CT by prolonging the dietary preparation protocol in cardiac sarcoidosis.

Patient preparation is crucial for reliable interpretation of cardiac inflammation FDG PET. We share our experience of improved reporting confidence and propose a simple approach of prolonging preparation (from 24 to 48 hours) with the high-fat, no-carbohydrate, and protein-permitted diet followed by fasting in cardiac sarcoidosis in cases with diffuse or focal-on-diffuse myocardial FDG uptake.

Technetium-99m-pyrophosphate imaging-based computed tomography-guided core-needle biopsy of internal oblique muscle in wild-type transthyretin cardiac amyloidosis

Background Technetium-99m-pyrophosphate (99mTc-PYP) uptake in the internal oblique muscle (IOM), which is often observed in patients with wild-type transthyretin cardiac amyloidosis (ATTR-CA), indicates amyloid transthyretin (ATTR) deposition. Objective This study aimed to assess the safety and efficacy of 99mTc-PYP imaging-based computed tomography (CT)-guided core-needle biopsy of the IOM as a new extracardiac screening biopsy for confirming the presence of ATTR deposits. Methods Patients with suspected ATTR-CA in whom myocardial tracer uptake was detected on chest- and abdomen-centered images of 99mTc-PYP scintigraphy underwent CT-guided core-needle biopsy at the site with the highest tracer uptake in the IOM between September 2021 and November 2022. Results All 18 consecutive patients (mean age, 86.3 years ± 6.5; 61.1% male) enrolled in the study showed 99mTc-PYP uptake into the IOM. Adequate tissue samples were obtained from all patients except one without serious complications. Immunohistochemical analysis confirmed ATTR deposits in 16/18 (88.9%) patients. In the remaining two patients, ATTR deposits were observed via endomyocardial biopsy. All patients were diagnosed with wild-type ATTR-CA based on transthyretin gene sequence testing results. Conclusion In wild-type ATTR-CA, 99mTc-PYP imaging-based CT-guided core-needle biopsy of the IOM could be used as an extracardiac screening biopsy to confirm the presence of ATTR deposits.

Cardiac fludeoxyglucose-18 positron emission tomography in genotype-positive arrhythmogenic cardiomyopathy

BackgroundMyocardial inflammation contributes to the pathogenesis of arrhythmogenic cardiomyopathy (ACM), a clinically and genetically heterogenous disorder. Due to phenotypic overlap, some patients with genetic ACM may be evaluated for an underlying inflammatory cardiomyopathy. However, the cardiac fludeoxyglucose (FDG) positron emission tomography (PET) findings in ACM patients have not been elucidated. MethodsAll genotype-positive patients in the Mayo Clinic ACM registry (n = 323) who received a cardiac FDG PET were included in this study. Pertinent data were extracted from the medical record. ResultsCollectively, 12/323 (4%; 67% female) genotype-positive ACM patients received a cardiac PET FDG scan as part of their clinical evaluation (median age at scan 49 ± 13 years). Amongst these patients, pathogenic/likely pathogenic variants were detected in LMNA (n = 7), DSP (n = 3), FLNC (n = 1) and PLN (n = 1). Of note, 6/12 (50%) had abnormal myocardial FDG uptake, including diffuse (entire myocardium) uptake in 2/6 (33%), focal (1–2 segments) uptake in 2/6 (33%) and patchy (3+ segments) in 2/6 (33%). Median myocardial standardized uptake value ratio was 2.1. Interestingly, LMNA-positive patients accounted for 3 out of 6 (50%) positive studies (diffuse uptake in 2 and focal uptake in 1). ConclusionAbnormal myocardial FDG uptake is common in genetic ACM patients undergoing cardiac FDG PET. This study further supports the role of myocardial inflammation in ACM. Further investigation is needed to determine role of FDG PET in diagnosis and management of ACM and investigate the role of inflammation in ACM.

Diagnostic values of delayed additional FDG PET/CT scan in the evaluation of cardiac sarcoidosis.

This study aimed to compare the contribution of 18F-fluorodepxyglucose (FDG) positron (PET)/ computed tomography (CT) acquisition of early and delayed scans in patients with cardiac sarcoidosis (CS). Twenty-three patients with CS (median age: 69years; 11 women) were retrospectively evaluated using dual-phase FDG PET/CT. All patients were instructed to consume a low-carbohydrate diet followed by fasting for 18h before FDG injection to reduce physiological myocardial uptake. PET/CT was acquired at 60min (early) and 100min (delayed) after FDG administration. Focal and focal on diffuse uptake on visual analysis was considered positive for CS. A semi-quantitative analysis was performed using the maximum standardized uptake value (SUVmax) of the cardiac lesion and the mean SUV (SUVmean) of the blood pool. Significant myocardial FDG uptake was observed in 21 patients (91.3%) in the early acquisition group and in 23 patients in the delayed scan group (100%). Compared to the early scan, the delayed scan showed a significantly higher SUVmax of the cardiac lesion [median, 4.0; IQR (interquartile range, 2.9 to 7.0) vs. 5.8 (IQR 3.7 to 10.1); P = 0.0030] and a significantly lower SUVmean of blood pool [median, 1.3 (IQR, 1.2 to 1.4) vs. 1.1 (IQR, 0.9 to 1.2); P < 0.0001]. Delayed FDG PET/CT acquisition improves detection accuracy in patients with CS compared to early scans with washout of the blood pool activity. Therefore, it can contribute to a more accurate assessment of CS.

Negative methylene diphosphonate scintigraphy in biopsy-confirmed hereditary transthyretin Ala117Ser cardiac amyloidosis: a case report

99mTc-pyrophosphate (99mTc-PYP) scintigraphy is highly sensitive and specific for the diagnosis of transthyretin cardiac amyloidosis (ATTR-CA). Commonly used alternative tracers included 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) and 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP). A 61-year-old Chinese man presented with signs indicative of left ventricular hypertrophy. Genetic testing revealed heterozygous transthyretin Ala117Ser mutation. Scintigraphy using 99mTc-methylene diphosphonate failed to show myocardial uptake. Five months later, the patient underwent permanent pacemaker implantation. Tafamidis was used irregularly, and the patient died 2 years later. 99mTc-methylene diphosphonate may not be appropriate for diagnostic use in ATTR-CA patient with transthyretin Ala117Ser mutation.

Synthetic Attenuation Correction Maps for SPECT Imaging Using Deep Learning: A Study on Myocardial Perfusion Imaging.

(1) Background: The CT-based attenuation correction of SPECT images is essential for obtaining accurate quantitative images in cardiovascular imaging. However, there are still many SPECT cameras without associated CT scanners throughout the world, especially in developing countries. Performing additional CT scans implies troublesome planning logistics and larger radiation doses for patients, making it a suboptimal solution. Deep learning (DL) offers a revolutionary way to generate complementary images for individual patients at a large scale. Hence, we aimed to generate linear attenuation coefficient maps from SPECT emission images reconstructed without attenuation correction using deep learning. (2) Methods: A total of 384 SPECT myocardial perfusion studies that used 99mTc-sestamibi were included. A DL model based on a 2D U-Net architecture was trained using information from 312 patients. The quality of the generated synthetic attenuation correction maps (ACMs) and reconstructed emission values were evaluated using three metrics and compared to standard-of-care data using Bland-Altman plots. Finally, a quantitative evaluation of myocardial uptake was performed, followed by a semi-quantitative evaluation of myocardial perfusion. (3) Results: In a test set of 66 test patients, the ACM quality metrics were MSSIM = 0.97 ± 0.001 and NMAE = 3.08 ± 1.26 (%), and the reconstructed emission quality metrics were MSSIM = 0.99 ± 0.003 and NMAE = 0.23 ± 0.13 (%). The 95% limits of agreement (LoAs) at the voxel level for reconstructed SPECT images were: [-9.04; 9.00]%, and for the segment level, they were [-11; 10]%. The 95% LoAs for the Summed Stress Score values between the images reconstructed were [-2.8, 3.0]. When global perfusion scores were assessed, only 2 out of 66 patients showed changes in perfusion categories. (4) Conclusion: Deep learning can generate accurate attenuation correction maps from non-attenuation-corrected cardiac SPECT images. These high-quality attenuation maps are suitable for attenuation correction in myocardial perfusion SPECT imaging and could obviate the need for additional imaging in standalone SPECT scanners.

Diagnostic and prognostic value of right ventricle uptake at 99m-PYP scintigraphy in patients with ATTR cardiac amyloidosis

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Pfizer. Introduction Bone-seeking tracers scintigraphy has assumed a central role in the diagnosis of Amyloid Transthyretin Cardiac Amyloidosis (ATTR-CA) since it is currently the only non-invasive imaging method capable of accurately diagnosing ATTR-CA. It is well known that right ventricle (RV) involvement is associated with poor clinical prognosis in patients with heart failure. Non-invasive imaging methods such as echocardiography and cardiac magnetic resonance have shown that RV involvement is common and related to poor outcomes. However, there is a paucity of data regarding scintigraphy in such a particular group of ATTR - CA patients. Purpose The present study was primarily designed to evaluate the diagnostic and incremental prognostic value of RV uptake of technetium-99m (99mTc) pyrophosphate (PYP) scintigraphy in ATTR-CA patients. Methods This is a prospective, observational, longitudinal study to evaluate clinical, laboratory and data obtained from non-invasive imaging methods for a period of 24 months. Only patients with a diagnosis of ATTR-CA suggested by scintigraphy and after ruling out monoclonal gammopathies were selected. Patients underwent 99mTc-PYP-scintigraphy and myocardial uptake was confirmed on planar images and SPECT/CT according to Perugini visual score. The primary outcome was a composite of cardiovascular death due to worsening of heart failure or fatal arrhythmia, atrial fibrillation and stroke. Results Ten subjects were included from August 2020 to October 2022. Median age of 72 years, all male and 5 (50%) African American. 8 (80%) patients had hereditary ATTR-CA and 2 (20%) ATTR-CA wild type. 5 (50%) had mild renal dysfunction and NYHA Class II or III was observed in 90% of the patients. Median levels of NT-pro-BNP and troponin were 1688,77 pg/ml (100–4545) and 0,084 ng/ml (0,064–0,123), respectively. Median Left Ventricle Ejection Fraction was 39,5 ± 7,86 (Simpson's) and median interventricular septum thickness was 16,1 ± 2,56 mm. Regarding scintigraphy results bi-ventricular (BIV) uptake was observed in 7 patients (70%). All patients had a grade 3 of Perugini score on left ventricle (LV) and the most common pattern of uptake was homogeneous and diffuse (70%). In patients with BIV the grade of Perugini score observed in RV was 57% (grade 3), 29% (grade 2) and 14% (grade 1) and the most common pattern of uptake was also homogeneous and diffuse (57%). Apex and mid-apex uptake was observed in 14% and 29% of patients, respectively. Three patients died during follow-up due to worsening of heart failure and cardiogenic shock: two in the group with BIV uptake and one in the group without right ventricle uptake at 99m-Tc-PYP scintigraphy. No statically significant difference was observed in the survival curve during follow up. Conclusions The prevalence of bi-ventriclular uptake on 99m-Tc-PYP- scintigraphy was high but was not related to a poor outcome of patients with ATTR-CA in our study.

Relationships between biventricular myocardial function and oxygen uptake during exercise in healthy adolescent male athletes

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): UK Research and Innovation Medical Research Council Doctoral Training Programme Grant Work supported as part of a research partnership between the University of Bristol and Canon Medical Systems UK that determines the independence of the research from either parties. Background Biventricular cardiac function improves with increasing work-rate during exercise in healthy elite athletes, but how it relates to concomitantly measured oxygen uptake (VO2) is not well known. Assessing cardiac determinants of cardiorespiratory fitness through multimodal evaluations may lead to improvements in clinical stress testing protocols and better understanding of exercise physiology. Purpose The aim of this study was to investigate whether left and right ventricular (LV and RV) systolic function measured by speckle tracking echocardiography (STE) at submaximal exercise (moderate and high intensity domains) is associated with concomitantly measured VO2 in healthy adolescent male athletes. Methods Elite male football players &amp;lt;16 years-old underwent cardiopulmonary exercise testing with concomitant STE at 50 W steps. Exercise intensity domains were defined based on the gas exchange threshold (GET). LV and RV free wall (FW) peak systolic longitudinal strain (Sl), strain rate (SRl) and LV average (12 mid and basal segments) circumferential strain (Sc) and strain rate (SRc) were measured. Cardiac function relation to peak VO2 was evaluated using linear regression, and its relationships to VO2 within each exercise intensity domain using repeated measures mixed linear models, before and after adjusting for heart rate (HR). Results A total of n=94 athletes were included (mean age 14.7 ± 1 years). Mean peak VO2 and work-rate were 43 ± 7 mL·min-1·kg-1 and 215 ± 40 W, respectively. Relationships between cardiac function and VO2, by exercise intensity domain are shown in Figure 1 with all regression coefficients shown in Table 1. Only LV Sl at high intensity was correlated to peak VO2 (p = 0.04). Within exercise intensity domains higher LV Sl (Figure 1A) and SRl (Figure 1B) were associated with higher concomitantly measured VO2 at both moderate and high intensity. Higher SRc (Figure 1C) and RV FW SRl (Figure 1F) were associated with higher VO2 only at moderate intensity. LV Sc (Figure 1C) and RV FW Sl (Figure 1E) were not associated with concomitant VO2 during exercise at moderate or high intensity. Only LV Sl and SRl at moderate and high intensity remained significantly associated to concomitantly measured VO2 after further adjusting by HR (Table 1). Conclusions In healthy adolescent athletes, only LV longitudinal strain and strain rate measured at moderate and high intensity were associated with VO2 independent of HR response. There were differences in myocardial response to exercise both between the two ventricles, and between the longitudinal and circumferential components of LV function. These require further research, both in healthy and disease groups, especially in RV pathology, where components of myocardial function could play different roles in limiting exercise capacity.

Cardiac fibroblast activation after acute myocardial infarction: pilot study using technetium 99m-iFAP SPECT

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Instituto Nacional de Investigaciones Nucleares (ININ). Background/Introduction Excessive fibrosis and persistent active fibroblasts can lead to increased left ventricular stiffness and, thus, heart failure. Cardiac remodeling is an important factor in the prognosis of patients after an acute myocardial infarction (AMI), and fibroblast activation is mandatory for repair and regeneration of the damage. There's an increasing use of molecular imaging in cardiovascular processes, such as molecules targeting fibroblast activation protein (FAP). FAP inhibitors (iFAP) radiolabeled with 68Ga in PET/CT have demonstrated adequate biodistribution and high uptake by activated fibroblasts in patients with cardiovascular risk factors and after acute myocardial infarction. Unfortunately, PET is not always widely available or cost-effective. Purpose This pilot study evaluates the feasibility of imaging activated fibroblast using 99mTc-iFAP SPECT in patients after AMI and its correlation with myocardial perfusion imaging (MPI), cardiac magnetic resonance (CMR) and invasive coronary angiography (ICA). Methods A prospective study with recent first AMI and non-previous known coronary artery disease patients were included. They underwent 99mTc-MIBI MPI SPECT and 99mTc-iFAP SPECT (including whole-body scan and thorax anterior static image acquired at 20, 60, and 120 min for the iFAP) and CMR/ICA within 14 days (+-2) after AMI. Qualitative and quantitative analysis was performed using a 17 segments model using QPS (Cedars Sinai) to determine the infarct extension from MPI and the correlation with the 99mTc-iFAP uptake pattern. A visual grading scale was established to assess localized tracer uptake and segments belonging to the hypoperfused area of the culprit's vessel. CMR yielded an area of injury with late gadolinium enhancement (LGE) and correlated with MPI studies. Results Five patients with STEMI were included (mean age of 63). Localized uptake of 99mTc-iFAP was observed in all patients with according to the affected coronary territory detected by ICA in 100% of patients (four anterior STEMI, one inferior STEMI). No radiotracer uptake was observed in the non-infarcted territories. Agreement between myocardial iFAP uptake, MIBI myocardial perfusion defect, CMR LGE, and ICA findings are presented in figure 1. An agreement of mismatch in polar maps between iFAP and MPI was performed, obtaining an excellent mismatch pattern in all patients, especially in transmural infarct segments. The best quality image was obtained at 60 minutes. Conclusions We successfully carried out the first pilot study with the patented 99mTc-iFAP molecule with SPECT technique. 99mTc-iFAP is a promising novel biomarker in assessing myocardial injury in sites where PET/CT is unavailable. There is an excellent correlation between iFAP uptake with the perfusion defect, LGE, and invasive anatomical obstruction findings. It is feasible and necessary to extend the inclusion of patients to a larger sample.

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

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Pfizer SLU Introduction Myocardial uptake on bone scintigraphy with diphosphonates has become a useful tool for the early detection of transthyretin cardiac amyloidosis (ATTR-CM), the prevalence of which remains unknown. Purpose To assess the prevalence of myocardial uptake in bone scintigraphy in patients without previous clinical suspicion of cardiac amyloidosis (CA). Methods Observational, retrospective, multicentre study in 21 hospitals across Spain, their reference population represented 24.38% of the total national population. All scans performed for non-cardiac reasons during the months of September, October and November 2019 were reviewed. Scans with positive cardiac uptake (Perugini scores 1-3) were evaluated by a central laboratory. Medical histories of the patients with positive uptake were reviewed. Results 9864 scans were reviewed. Cardiac uptake was observed in 71 patients (0.72%) over 18 years of age (85.90% male). According to the central laboratory assessment the distribution in the Perugini grading scale was, grade 1 (23.90%), grade 2 (29.60%) and grade 3 (46.50%). No relationship between sex and Perugini grade was observed. Heart/Contralateral ratio (H/CL) was available for 24 patients with a mean of 2.1 ± 1.1 (95% CI 1.7–2.6). A third of the patients (33.80%) also presented extracardiac uptake, being the most common: bone metastasis (7.04%) abdominal wall (5.60%) and lower limbs muscular mass (4.20%). A previous heart failure (HF) diagnosis was found in the 16.90% of the patients with positive uptake, being most of them 57.10% in NYHA class II. Patients ≤ 80 y.o. were diagnosed with heart failure earlier than patients &amp;gt; 80 y.o. (p = 0.02) and with atrial fibrillation earlier than patients &amp;gt; 80 y.o. (p = 0.05). Ten patients with cardiac uptake were subsequently diagnosed with ATTR amyloidosis (ATTR-Y) with a mean delay of 10.8 months (95% CI: 6.0–16.8). All ATTR-Y patients were &amp;gt; 70 y.o., 90.00% were male, had left ventricular hypertrophy (LVH) compared to 25.49% of patients in whom a diagnosis of ATTR (ATTR-N) was not confirmed (p = 0.00003). Patients in the ATTR-Y group presented some episode of orthostatic hypotension and involuntary weight loss in the clinical history (30.00% in both) compared to 3.77% (p = 0.025) and 5.88% (p = 0.05) of the ATTR-N group respectively. Conclusions This national study found a prevalence of 0.72% of incidental cardiac uptake in bone scintigraphies performed for non-cardiac reasons in adult patients. The results of this study bring light on the profile of the elderly patients with incidental cardiac uptake. The referral of these patients can facilitate the early diagnosis of CA with the consequent impact on the management and prognosis of patients.

Regression of Myocardial 99mTc-DPD Uptake After Tafamidis Treatment of Cardiac Transthyretin Amyloidosis.

Cardiac transthyretin amyloidosis is an infiltrative cardiomyopathy with high mortality. To date, there are no specific biomarkers to directly assess disease activity and response to specific treatments. Our aim was to evaluate scintigraphic changes after treatment with the transthyretin stabilizer tafamidis. Methods: We included patients who had undergone 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy before tafamidis initiation and after at least 9 mo. Tracer activity was assessed visually and quantitatively as SUVmax Results: The study included 14 patients who were on tafamidis for 44 ± 14 mo. We observed regression of Perugini grade in 5 patients, unchanged grade in 9 patients, and regression of mean heart-to-contralateral-lung ratio (P = 0.015) and SUVmax (P = 0.005). There were no changes in N-terminal pro-B-type natriuretic peptide or echocardiographic measures. Conclusion: Treatment with tafamidis results in regression of myocardial 99mTc-DPD uptake. 99mTc-DPD scintigraphy may provide useful imaging biomarkers to assess response to treatment.