Tc-99m Pyrophosphate Research Articles

“Red Flags”: Case Report of Cardiac Amyloidosis with Significant Coronary Artery Disease

BACKGROUND: Cardiac Amyloidosis is a disorder of protein misfolding and metabolism in which insoluble fibrils are deposited in the myocardial extracellular matrix causing organ dysfunction and eventually death. It can exhibit cardiac signs and symptoms, or it can be identified through screening in patients who exhibit extracardiac symptoms of amyloidosis. As there were no clear clinical signs of cardiac amyloidosis and a biopsy is required to show amyloid deposition, the condition has been historically challenging to diagnose. Thus, a high index of suspicion based on the clinical presentation and the outcomes of the preliminary testing arecrucial to determine the approach to diagnosis. CASE SUMMARY: We outline a case of 75-year-old Filipino male who was admitted due to progressive exertional dyspnea. Cardiac Amyloidosis was considered due to evaluation findings of heart failure with preserved ejection fraction with restrictive type of cardiomyopathy. This was subsequently confirmed through extracardiac fat pad biopsy, echocardiographic strain analysis and Technetium (99mTc) Pyrophosphate (PYP) single photon emission computed tomography scan (SPECT). CONCLUSION: This case report discussed the red flags of clinical manifestations of cardiac amyloidosis and highlighted the use of non-invasive diagnostic modalities to diagnose the disease. Cardiac amyloidosis remains a rare entity and with emerging therapies that have the potential to improve patient outcomes, early diagnosis is really important. Having high index of suspicion based on signs and symptoms can lead to early detection and an increased number of patients being referred for treatment.

Race, Sex, and Ejection Fraction-Based Differences in Transthyretin Amyloid Cardiomyopathy (ATTR-CM) Risk Prediction

Background: The early detection of transthyretin cardiac amyloidosis (ATTR-CM) is essential, with Tc-99m pyrophosphate scintigraphy (PYP scan) being a key diagnostic tool. Although a previously validated score has shown promise in predicting PYP scan positivity among patients with HFpEF, further evaluation in diverse cohorts is necessary. Objectives: To assess the effectiveness of the ATTR-CM score in predicting PYP scan positivity within our patient population. Methods: We analyzed patients referred for PYP with SPECT at the Cleveland Clinic from January 2012 to January 2020, all of whom had undergone echocardiography within the previous year. The ATTR-CM score was determined using the following criteria: Age (60–69, +2; 70–79, +3; ≥80, +4), sex (male, +2), hypertension (present, −1), left ventricular ejection fraction (LVEF <60%, +1), posterior wall thickness (≥12 mm, +1), and relative wall thickness (>0.57, +2). A score of ≥6 indicated high risk. Results: Among the 540 patients (32% female, 33% black), 27% had an LVEF <40%. The score demonstrated good discrimination by AUC, with consistent performance across different racial groups, sexes, and LVEF categories. For scores ≥6, sensitivity was lower in women and black patients; however, lowering the cutoff to 5 markedly improved sensitivity. Conclusions: The ATTR-CM score displayed consistently good performance by AUC across our cohort, including patients with HFrEF. Nevertheless, its sensitivity was reduced in black patients and women. Efforts to scale ATTR-CM diagnosis tools should be mindful of demographic differences in risk prediction models.

Regional variation in technetium pyrophosphate (PYP) uptake in transthyretin cardiac amyloidosis (ATTR-CA) and concomitant myocardial infarction: A case series

- Diffuse and patchy myocardial uptake of Tc-99m PYP is well established in cases of ATTR-CA. - Chronic myocardial infarction leads to regional myocardial thinning and lack of vascular supply can present as regional sparing 'cold spot' on Tc-99m PYP imaging. - The absence of Tc-99m PYP uptake in vascular regions should raise the possibility of underlying scar.

Right Ventricular Strain Improves the Echocardiographic Diagnosis and Risk Stratification of Transthyretin Cardiac Amyloidosis Among Other Phenotypes of Left Ventricular Hypertrophy

Cardiac amyloidosis is a diffuse disease affecting all cardiac chambers. The value of right ventricular free-wall strain is uncertain as an echocardiographic red flag. We hypothesized that right ventricular free-wall strain is of added value for diagnostic and prognostic purposes in patients with transthyretin cardiac amyloidosis (ATTR-CA). A diagnosis of ATTR-CA required positive Tc-99m pyrophosphate scintigraphy and negative serum clonal dyscrasia. Patients with left ventricular (LV) hypertrophy (LVH; interventricular septal thickness ≥1.2cm) by echocardiography and negative pyrophosphate scintigraphy served as controls after exclusion of amyloid light-chain cardiac amyloidosis. Longitudinal strain was computed with speckle-tracking echocardiography. We studied 108 subjects with ATTR-CA and 106 controls with LVH, retrospectively. Right ventricular free-wall strain was independently associated with the diagnosis of ATTR-CA after adjusting for classical echocardiographic parameters, namely, relative apical sparing (RAS), e', and E/e'. Right ventricular free-wall strain≥-16% was incremental to LV RAS in the overall group and in the subgroup without extreme wall thickness (≤1.4cm; Harrell's C, net reclassification improvement=0.213, P<.001; and net reclassification improvement= 0.463, P=.015, respectively). Major adverse cardiovascular and cerebrovascular events (heart failure hospitalization, stroke, death) occurred in 47 ATTR-CA patients, during follow-up (median, 38; range, 6-60months). Right ventricular free-wall strain≥-16% was associated with 3-fold increased risk of MACCE in ATTR-CA patients independently of age, comorbidities, B-type natriuretic peptide, and tafamidis treatment. Right ventricular free-wall strain was additive to LV ejection fraction for risk stratification (chi square =10.2; P=.017). Right ventricular free-wall strain>-16% has incremental value to LV RAS for the differential diagnosis of ATTR-CA among LVH phenotypes and is associated with poor prognosis.

Predictive Value of high-sensitivity cardiac troponin T in patients undergoing 99mTc pyrophosphate scintigraphy for suspected transthyretin amyloid cardiomyopathy

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure (1,2). 99mTc- pyrophosphate cardiac scintigraphy (PYP) enables accurate, noninvasive diagnosis of ATTR-CM when coupled with appropriate clinical and laboratory evaluations to rule out light chain amyloidosis (3,4). High sensitivity cardiac troponin T (hs-cTnT) is routinely assessed for diagnostic purposes when ATTR-CM is suspected in clinical practice. Purpose To investigate the diagnostic performance of hs-cTnT in patients undergoing PYP for suspected ATTR-CM. Methods Observational study of patients undergoing PYP at a United States (US) cardiac amyloidosis referral center from 2013 to September 2022 and with at least one hs-cTnT value available within 1 year. 3-hour planar imaging followed by single photon-emission computed tomography with computed tomography was performed. Final diagnoses of ATTR-CM were validated using all clinical information. The lowest reportable clinical value for hs-cTnT in the US is &amp;lt;6 ng/L (limit of quantitation). Results A total of 1572 patients underwent PYP and had a hs-cTnT value available within the study period. Of these, ATTR-CM was diagnosed in 475 patients (30%). Median (IQR) hs-cTnT was 48 (31-67) ng/L in patients with ATTR-CM and 26 (13-48) ng/L in those without. The area under the curve of hs-cTnT for the diagnosis of ATTR-CM was 0.69 (0.67-0.72). Among patients with a very low hs-cTnT value, i.e. &amp;lt;6 ng/L (n=100, 6.4% of the overall cohort), 7 (7%) patients had a final ATTR-CM diagnosis while 93 (93%) did not. Therefore, a threshold of &amp;lt;6 ng/L demonstrated a negative predictive value (NPV) of 93% (IQR 88, 98) and a sensitivity of 99% (97, 100) for ruling out ATTR-CM. The highest NPV was achieved with a threshold of 12 ng/L; 269 (17%) patients had hs-cTnT below this value and, of those, only 16 (6%) had a final diagnosis of ATTR-CM. This resulted in a NPV of 94% (91, 97) and a sensitivity of 97% (95, 98) for ruling out ATTR-CM. When considering progressively increasing hs-cTnT values as potential thresholds to aid in the prediction of ATTR-CM (Figure), we observed a progressive increase in specificity (above 90% for hs-cTnT values &amp;gt; 95 ng/L), but the positive predictive value (PPV) remained low (below 50%). Conclusions Among patients undergoing PYP for suspected ATTR-CM at a US referral center, a very low hs-cTnT value was present in a minority of patients but demonstrated good performance in ruling out ATTR-CM. The highest NPV (94%) was achieved with a threshold of &amp;lt; 12 ng/L. Higher hs-cTnT values showed a good specificity, but PPV remained low. Therefore, while a very low hs-cTnT might be of help in identifying those at low risk of ATTR-CM, the ubiquitous presence of increased hs-cTnT in many of these patients suggests the need for a multiparametric diagnostic approach to make the diagnosis.hs-cTnT in patients undergoing PYP scan

Abstract 17110: Racial Differences in the Performance of the Transthyretin Amyloid Cardiomyopathy Risk Score

Introduction: Early diagnosis of transthyretin cardiac amyloidosis is crucial, particularly with the availability of disease-modifying therapies. Tc-99m pyrophosphate scintigraphy (PYP scan) is widely used for diagnosis. A previously validated score derived from a nearly all Caucasian cohort has shown promise in predicting PYP scan positivity in patients with HFpEF; but further assessment in a racially diverse cohort is needed. Aims: To evaluate the performance of the ATTR-CM score in predicting PYP scan positivity overall, and across racial groups. Methods: We included all patients referred for PYP with SPECT/CT at the Cleveland Clinic between 1/2012 and 1/2020 who had undergone echocardiography within one year of PYP scan. The ATTR-CM score was calculated, consisting of the following variables: Age (if 60-69, +2; if 70-79, +3; if ≥80, +4), Sex (if Male, +2), Hypertension diagnosis (if present, -1), Ejection Fraction (if &lt;60%, +1), Posterior Wall Thickness (if ≥12 mm, +1) and Relative Wall Thickness (if &gt;0.57, +2). A score ≥6 was considered high-risk. Results: The cohort consisted of 540 patients (64% white; 33% black). The overall prevalence of ATTR-CM was 28.5%, with no significant difference between racial groups (27.5% vs 29.9%; p = 0.52). A higher proportion of black patients had an EF &lt; 40% (23.3% vs 35.4%, p = 0.01). The score showed good discrimination with an AUC of 0.816, with similar performance between racial groups (0.824 vs. 0.824; p &lt; 0.001; Figure 2). For a score ≥6, sensitivity was 77.3% (82.7% white; 67.3% black), specificity was 70.2% (64.3% white; 80.6% black), PPV was 50.9%, and NPV was 88.6%. Similar findings were observed when considering only patients with EF ≥ 40%. Conclusions: The overall performance of the ATTR-CM risk score by AUC was consistently good across races. However, it was less sensitive for detecting disease in black patients. Efforts to scale ATTR-CM diagnosis tools should be mindful of racial differences in risk prediction models.

Current status and perspectives of nuclear cardiology.

Nuclear cardiology has long been used to identify myocardial ischemia for appropriate treatment strategies for stable coronary artery disease (CAD). After the Ischemia Trial, it is time to reevaluate the significance of ischemia assessment. Functional imaging continues to play pivotal role in detecting microcirculatory disturbances. PET provides a clear image of blood flow distribution and is useful for the quantitative evaluation of myocardial flow reserve (MFR), which plays an important role in predicting treatment strategies and improving prognosis in CAD. Heart failure has become a major area of focus in cardiovascular medicine. Radionuclide imaging has been widely applied in this field. FDG PET is useful in identifying cardiac sarcoidosis and active inflammation. Clinical values of I-123 MIBG and BMIPP SPECT have been reported worldwide from Japan. Additionally, clinical experiences of Tc-99m pyrophosphate imaging have recently gained attention for assessing cardiac amyloidosis. Cardiac PET/CT and PET/MR imaging permit combined assessment of metabolic/functional/structural analyses of various cardiac diseases. While other non-invasive imaging modalities have rapidly been developed, the roles of radionuclide imaging remain to be valuable for early and accurate diagnosis and patient management in most cases of chronic CAD and various cardiovascular diseases.

Use of SPECT imaging to confirm ATTR cardiac amyloid in a Tc99m pyrophosphate study artefactually compromised by a recent V/Q scan

Use of SPECT imaging to confirm ATTR cardiac amyloid in a Tc99m pyrophosphate study artefactually compromised by a recent V/Q scan

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.

In the thick of it: hereditary cardiac amyloidosis identified by 124I-AT-01 PET imaging but not cardiac MRI or SPECT 99mTc pyrophosphate scintigraphy

In the thick of it: hereditary cardiac amyloidosis identified by 124I-AT-01 PET imaging but not cardiac MRI or SPECT 99mTc pyrophosphate scintigraphy

Follow-up Tc-99m pyrophosphate cardiac scan for patients with transthyretin cardiac amyloidosis treated with tafamidis.

Tafamidis has been used for treatment of transthyretin cardiac amyloidosis (ATTR-CA). However, Tc-99m pyrophosphate (PYP) cardiac scan for follow-up after tafamidis therapy has not been reported. From May 2017 to March 2022, five patients with or without tafamidis therapy had received two Tc-99m PYP cardiac scans. Tc-99m PYP cardiac scan was performed with planar image and single photon emission computed tomography/computed tomography (SPECT/CT) 3h after administration of Tc-99m PYP. Perugini grading system was applied to determine positive or negative result of the scan. Heart to contralateral lung (H/CL) ratio as well as the difference of H/CL ratio between first and second Tc-99m PYP cardiac scans (ΔH/CL ratio) was calculated. In the five patients participated in this study, three received tafamidis therapy and H/CL ratio was significantly decreased (p = 0.02) after tafamidis therapy. Besides, the ΔH/CL ratio was larger in patients with tafamidis therapy than that in those without tafamidis therapy, albeit not reaching statistical significance (p = 0.2). A decrease in H/CL ratio was found after tafamidis therapy in patients with ATTR-CA, albeit the magnitude of changes in the H/CL ratio (ΔH/CL ratio) was not significantly different from that of patients without tafamidis therapy. Future study with larger population might be required to further clarify the effect of tafamidis therapy on myocardial uptake of Tc-99m PYP. No clinical trial was conducted in our retrospective study.

Towards a Diagnosis of Cardiac Amyloidosis: Single Center Experience with 99m Technetium Pyrophosphate Planar Imaging and Opportunities for Standardization of Diagnostic Workflow.

Background and Objectives: Cardiac amyloidosis is a disorder caused by amyloid fibril deposition in the extracellular space of the heart. Almost all forms of clinical cardiac amyloidosis are transthyretin amyloidosis (ATTR) or light chain amyloidosis. 99m technetium pyrophosphate (99mTc PYP scan) has changed the landscape of the non-biopsy diagnosis of ATTR cardiac amyloidosis (ATTR-CA) by providing remarkably high diagnostic accuracy. We examined our experience with PYP scans in patients undergoing workup for ATTR-CA and evaluated the diagnostic workflow in patients with intermediate PYP scan results. Materials and Methods: Retrospective chart review study in which we analyzed data of 84 patients who underwent c-99m pyrophosphate (PYP) SPECT scan for the diagnosis of ATTR-CA from 2017 till 2021 at our institution. We identified three groups: Low uptake (PYPL uptake ratio < 1.2 + visual grade 1/0), n = 30, Intermediate uptake (PYPI uptake ratio 1.2-1.49, visual grade 2/3), n = 25 and High uptake (PYPH uptake ratio ≥ 1.5 + visual grade 2/3), n = 29. We reviewed patients' demographics, medical histories, echo parameters and diagnostic testing including light chain analysis, cardiac magnetic resonance results, and biopsies. Results: Mean patients' age was 73, male-to=female ratio 3:1, 59% of patients were African American. Cardiovascular comorbidities, cardiac biomarkers (BNP and Troponin) and amyloid-related neuropathy were similar in all groups. A statistically significant difference in septal thickness/posterior wall thickness and final diagnosis were found between the groups. The distribution of overall diagnostic testing ratios for the PYPI group included serum protein electrophoresis 92%, urine protein electrophoresis 65%, free light chain 80%, CMR 32%, tissue biopsy done in 20% and BM biopsy in 16%, which are similar to the ratios of other groups. Overall, 25% (n = 5, 4 TTR-CA and 1 AL Amyloid) of patients in the PYPI group had a final diagnosis of CA established with additional testing (p = 0.001 vs. other groups). Conclusions: The 99mPYP scan is an accurate noninvasive test for cardiac ATTR-CA. Importantly, 25% of the PYPI group had a final diagnosis of ATTR-CA reiterating that diagnosis needs to be pursued in PYPI cases based on clinical suspicion. Routine evaluation and exclusion of light chain disease and establishing a consistent workflow for amyloid diagnosis and continued education for technologists and readers of PYP scans is key to a successful amyloidosis workup.

Serum amyloidosis: a cardiac amyloidosis.

A 75-year old male with a history of membranoproliferative glomerulonephritis requiring kidney transplant, carpal tunnel, and peripheral neuropathy presented with new heart failure. An echocardiogram revealed moderate, concentric left ventricular hypertrophy (LVH) despite normal electrocardiographic voltage. To evaluate for the aetiology of unexplained LVH, a cardiac magnetic resonance (CMR) was performed which showed increased wall thickness with markedly increased T1 relaxation time and extensive, near-transmural late gadolinium enhancement throughout the myocardium (Panels A–C, green arrows), findings highly concerning for cardiac amyloidosis (CA). Despite this, a 21.5 mCi Tc-99 m pyrophosphate (Tc-PyP) scan and comprehensive serum (Panels D and E) and urine light chain analysis showed no evidence of transthyretin or immunoglobulin light chain CA, respectively. Despite these negative findings, the patient was referred for endomyocardial biopsy due to high clinical concern for CA. His biopsy revealed diffuse myocardial amyloid deposition (Panels E and F) which was ultimately identified as serum amyloid A (AA) protein on mass spectrometry. AA-CA is a rare form of cardiac amyloidosis caused by deposition of SAA protein—an acute phase reactant—in the myocardium. This disorder is most commonly observed in patients with longstanding chronic inflammatory conditions and is frequently missed by conventional light chain and Tc-PyP analysis. Renal dysfunction is a key feature of AA-CA and is present in a most cases. This case highlights the importance of having a low threshold to pursue further testing including invasive tissue biopsy when typical CA CMR features are present even in the absence of confirmatory non-invasive testing.

99mTc Bone-Avid Tracer Cardiac Scintigraphy: Role in Noninvasive Diagnosis of Transthyretin Cardiac Amyloidosis.

Transthyretin cardiac amyloidosis (ATTR-CA) is an overlooked cause of heart failure, with substantial morbidity and mortality. The emergence of several novel therapies has fueled the interest in early and accurate diagnosis of ATTR-CA so that potentially life-saving pharmacologic therapy can be administered in a timely manner. The most promising imaging modality and biomarker is SPECT imaging with technetium 99m (99mTc)-radiolabeled bone-seeking tracers, which have high specificity in the diagnosis of ATTR-CA, potentially obviating biopsy. In this article, the authors provide a focused review on the use of 99mTc pyrophosphate (PYP), 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), and hydroxymethylene diphosphonate (HMDP) for diagnosis of ATTR-CA, present a systematic approach to interpretation of the scans, and highlight several common pitfalls to illustrate important diagnostic principles for accurate interpretation of these images. The authors indicate when to use endomyocardial biopsy for the diagnosis of cardiac amyloidosis and conclude with a section on quantitation of 99mTc-PYP/DPD/HMDP imaging.

Quantitative technetium pyrophosphate and cardiovascular magnetic resonance in patients with suspected cardiac amyloidosis

BackgroundQuantitation of myocardial 99m Tc-pyrophosphate activity may have high diagnostic accuracy, but its correlation with disease burden is unknown. We examined the relationship between 99m Tc-pyrophosphate quantitation and cardiac magnetic resonance (CMR) measures in patients with suspected transthyretin cardiac amyloidosis (ATTR-CM) or light chain cardiac amyloidosis (AL-CM). MethodsConsecutive patients who underwent 99mTc-pyrophosphate imaging and CMR were included. ATTR-CM and AL-CM were diagnosed using standard criteria. 99mTc-pyrophosphate images were assessed with standard parameters and quantified with cardiac pyrophosphate activity (CPA) and volume of involvement (VOI). We assessed the association between 99mTc-pyrophosphate image interpretation and CMR tissue characteristics. ResultsSeventy patients were identified, mean age 70.4 ± 11.4 years, with ATTR-CM and AL-CM diagnosed in 22 (31%) and 11 (16%) patients, respectively. In patients with ATTR-CM, there were significant correlations between CPA (r2 = 0.509, P < 0.001) and VOI (r2 = 0.586, P < 0.001) with native myocardial T1 mapping values. Additionally, CPA (adjusted hazard ratio (aHR) 1.04, P = 0.016), VOI (aHR 1.12, P = 0.034), and average myocardial T1 (aHR 1.12, P = 0.025) were associated with incidence of heart failure hospitalization or death. ConclusionCPA and VOI were correlated with CMR measures of myocardial fibrosis in patients with ATTR-CM. 99mTc-pyrophosphate quantitation may have a role in ATTR-CM disease staging, guiding treatment, or following response to therapy.

Tc-99m pyrophosphate left atrial uptake in patients with atrial fibrillation and cardiac amyloidosis

Tc-99m pyrophosphate left atrial uptake in patients with atrial fibrillation and cardiac amyloidosis

Tc-99m pyrophosphate scintigraphy for cardiac amyloidosis: concordance between planar and SPECT/CT imaging.

The imaging protocol and the optimal cut-off points for quantitative assessment of technetium-99m pyrophosphate (Tc-99m PYP) cardiac amyloidosis scintigraphy remain controversial. The aim of this study was to evaluate the concordance between planar and SPECT images, and to investigate the contribution of SPECT/CT to diagnostic precision. All patients referred to our department for Tc-99m PYP cardiac imaging between April 2019 and April 2022 were included in the study. Heart-to-contralateral lung (H/CL) ratios were calculated from anterior planar images at both 1- and 3h, and visual grading was done in SPECT/CT images at both time points. A total of 141 patients were included in the study (median age 59years, 54% female). There was a strong positive correlation between H/CL ratios calculated at 1- and 3h (Pearson's ρ = 0.842, p < 0.001). The highest level of concordance between planar and SPECT/CT images was achieved at a H/CL cut-off point of 1.5 for 1-h images, and 1.4 for 3-h images. SPECT/CT imaging contributed to diagnostic precision in both 1- and 3-h images by reducing the rate of equivocal results from 83% (n = 117) to 25% (n = 35), and from 77% (n = 108) to 27% (n = 38), respectively. Our findings have three implications: (1) planar imaging at both 1- and 3h could be redundant, (2) a lower H/CL cut-off point for 3-h planar images could improve concordance between planar and SPECT imaging, and (3) SPECT/CT in both 1- and 3h could improve the diagnostic precision by offering markedly reduced equivocal results.

Development and feasibility of quantitative dynamic cardiac imaging for mice using μSPECT

BackgroundDespite growing interest in coronary microvascular disease (CMVD), there is a dearth of mechanistic understanding. Mouse models offer opportunities to understand molecular processes in CMVD. We have sought to develop quantitative mouse imaging to assess coronary microvascular function. MethodsWe used 99mTc-sestamibi to measure myocardial blood flow in mice with MILabs U-SPECT+ system. We determined recovery and crosstalk coefficients, the influx rate constant from blood to myocardium (K1), and, using microsphere perfusion, constraints on the extraction fraction curve. We used 99mTc and stannous pyrophosphate for red blood cell imaging to measure intramyocardial blood volume (IMBV) as an alternate measure of microvascular function. ResultsThe recovery coefficients for myocardial tissue (RT) and left ventricular arterial blood (RA) were 0.81 ± 0.16 and 1.07 ± 0.12, respectively. The assumption RT = 1 − FBV (fraction blood volume) does not hold in mice. Using a complete mixing matrix to fit a one-compartment model, we measured K1 of 0.57 ± 0.08 min−1. Constraints on the extraction fraction curve for 99mTc-sestamibi in mice for best-fit Renkin–Crone parameters were α = 0.99 and β = 0.39. Additionally, we found that wild-type mice increase their IMBV by 22.9 ± 3.3% under hyperemic conditions. ConclusionsWe have developed a framework for measuring K1 and change in IMBV in mice, demonstrating non-invasive µSPECT-based quantitative imaging of mouse microvascular function.

The role of the autonomic nervous system in stress cardiomyopathy

Aim. To identify the role of the autonomic nervous system in stress cardiomyopathy in an experimental model of Takotsubo syndrome.Materials and methods. The study was carried out on 120 female Wistar rats. Stress modeling was performed by immobilizing animals on the back for 24 hours. Intact rats were used as controls. The rats were decapitated after termination of immobilization under general anesthesia with ether. Stress cardiomyopathy (SCM) was quantified by accumulation of 99mTc pyrophosphate radiopharmaceutical (99mTc PP) in the myocardium. The pharmacological agents used included the ganglionic blocker hexamethonium, administered five times at a dose of 20 mg / kg; guanethidine (50 mg / kg) administered subcutaneously once a day for three days, the last injection was performed 24 hours before immobilization; the muscarinic receptor antagonist atropine methyl nitrate (1 mg / kg); the α1-AR (adrenergic receptor) antagonist prazosin (2 mg / kg); the α2-AR antagonist yohimbine, administered at a dose of 2 mg / kg; the β1-AR antagonist nebivolol (1.2 mg / kg); the β2-AR antagonist ICI 118,551 (0.3 mg / kg); and the β3-AR antagonist L-748337 (0.1 mg / kg).Results. Three-day administration of guanethidine caused a decrease in the degree of 99mTc-PP accumulation in the heart by 35.9%. Hexamethonium did not affect the degree of SCM. The blockade of the muscarinic receptor caused an increase in accumulation of 99mTc-PP by 26.5%. Inhibition of α1-AR did not affect SCM. The blockade of α2-AR caused a 2.2-fold increase in the accumulation compared with stress control. The blockade of β1-AR reduced 99mTc-PP accumulation by 2.5 times. The blockade of β2-AR by ICI 118,551 increased the degree of 99mTcPP accumulation by 34.6%. Inhibition of β3-AR had no effect on SCM.Conclusion. The adrenergic system and β1-adrenergic receptor play an important role in the development of SCM. The parasympathetic nervous system ensures resistance of the heart to stress.

False positive technetium-99m pyrophosphate scintigraphy in a patient with cardiac amyloidosis light chain

Introduction:Patients with cardiac amyloidosis light chain (AL) present with negative Tc-99m pyrophosphate (PYP) scintigraphy (absent or mild heart uptake). On the contrary, patients with cardiac amyloidosis transthyretin (ATTR) present with positive Tc-99m PYP scanning (intensive heart uptake). We present a false positive Tc-99m PYP scintigraphy (grade 2, the heart-to-contralateral ratio is 1.65) in a patient with AL.Patient concerns:A 42-year-old Chinese man complained of effort intolerance, chest discomfort, and short of breath progressively over 1 year. New York Heart Association Class III. Physical examination showed legs swelling. Laboratory revealed elevated brain natriuretic peptide of 23,031 ng/mL (0–88) and Troponin-T of 273.4 ng/mL (0–14).Diagnosis:Cardiac amyloidosis light chain. Evidences: free light chains (FLCs): decreased serum free kappa/lambda ratio of 0.043 (0.31–1.56). Immunofixation electrophoresis: a positive lambda light chain monoclonal protein. Cardiac biopsy: HE: Ambiguity Congo red strain. Myocardial immunofluorescence: positive lambda light chain. Myocardial immunohistochemistry: positive lambda light chain, negative kappa light chain, and TTR.Interventions:Furosemide 40 mg qd, torasemide 20 mg qd, spirolactone 20 mg qd, potassium chloride 10 mL per 500 mL urine, atorvastatin calcium tablet 20 mg qd, aspirin enteric-coated tablets 100 mg qd during the 2-weeks in-hospital.Outcomes:The patient died 2 months later after discharge.Conclusion:False positive Tc-99m PYP scintigraphy may rarely presented in patients with cardiac amyloidosis light chain. So, the clonal plasma cell process based on the FLCs and immunofixation is a base to rule out AL cardiac amyloidosis when we interpret a positive Tc-99m PYP scintigraphy.