Tawakol A, Ribaudo H, McKhann A
… +10 more, Bellinge JW, Zureigat H, Fayad ZA, Lederman MM, Grinspoon SK, Kuritzkes DR, Stein JH, Ridker PM, Currier JS, Hsue P
J Nucl Cardiol
· 2026 Jun · PMID 41389925
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[Image: see text] The central illustration displays the flow of study participants and the results of the primary endpoint. The individual baseline and follow-up MDS TBR are presented as red (LDMTX) or blue (Placebo) slo...[Image: see text] The central illustration displays the flow of study participants and the results of the primary endpoint. The individual baseline and follow-up MDS TBR are presented as red (LDMTX) or blue (Placebo) slope charts, along with the mean and standard deviation from each group at week 0 and week 24. A waterfall plot displays the absolute change in MDS TBR for each individual participant, colored by treatment group. An example of an FDG PET study of a subject with HIV who has heightened arterial inflammation that persists over time. HIV: Human immunodeficiency virus, 18F-FDG: 18F-Fluorodeoxyglucose, LDMTX: Low dose Methotrexate, PET: Positron Emission Tomography, CT: Computed Tomography, MDS: Most diseased segment, TBR: Tissue to Background.
Nishi T, Ota S, Shiono Y
… +16 more, Takano Y, Taniguchi M, Taruya A, Wada T, Takahata M, Ozaki Y, Kashiwagi M, Kuroi A, Yamano T, Tanimoto T, Takemoto K, Kitabata H, Takahashi Y, Nishikawa M, Murata S, Tanaka A
BACKGROUND: Early diagnosis of transthyretin-amyloid cardiomyopathy (ATTR-CM) is key to early treatment initiation. Recent guidelines recommend using both single-photon emission computed tomography (SPECT) and planar ima...BACKGROUND: Early diagnosis of transthyretin-amyloid cardiomyopathy (ATTR-CM) is key to early treatment initiation. Recent guidelines recommend using both single-photon emission computed tomography (SPECT) and planar imaging. However, whether combined use of planar imaging and SPECT improves diagnostic accuracy compared with histological confirmation is unclear. We assessed the significance of using both planar imaging and SPECT with bone-seeking tracer cardiac scintigraphy for diagnosing endomyocardial biopsy (EMB)-proven ATTR-CM. METHODS AND RESULTS: This retrospective observational study included 117 consecutive patients with suspected ATTR-CM who underwent bone-seeking tracer cardiac scintigraphy, among whom 42 underwent EMB based on positive planar imaging (Perugini grade ≥2) and/or positive SPECT results (uptake score ≥1). Of these 42 patients, 38 (91%) were histologically diagnosed with ATTR-CM. Among patients with concordantly positive planar imaging and SPECT, 36/37 (97%) were diagnosed with ATTR-CM. Among patients with discordant findings, 2/2 (100%) with negative planar but positive SPECT findings were diagnosed with ATTR-CM, whereas 0/3 (0%) with positive planar but negative SPECT findings were diagnosed with ATTR-CM. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SPECT for detecting transthyretin amyloid deposition on EMB were 100%, 75%, 97%, 100%, and 98%, respectively. On SPECT, tracer uptake was consistently and maximally observed in the interventricular septum in all cases of EMB-proven ATTR-CM (P < 0.001). CONCLUSIONS: SPECT has a high diagnostic ability in detecting EMB-proven ATTR-CM and effectively complements planar imaging by mitigating its limitations, reducing both false-positive and false-negative findings of planar imaging alone.
Tersalvi G, Carey P, Garmany A
… +16 more, Scott CG, Davies DR, Jouni H, Rodriguez-Porcel MG, Askew JW, Bois JP, Young KA, Anavekar NS, Chang IC, Pellikka PA, Grogan M, Dispenzieri A, Homb AC, Johnson GB, Chareonthaitawee P, AbouEzzeddine OF
BACKGROUND: Cardiac amyloid radionuclide imaging (CARI) with Tc-pyrophosphate (PYP) enables the noninvasive diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM). Recent PYP shortages have necessitated substitution...BACKGROUND: Cardiac amyloid radionuclide imaging (CARI) with Tc-pyrophosphate (PYP) enables the noninvasive diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM). Recent PYP shortages have necessitated substitution with Tc-hydroxymethylene diphosphonate (HMDP), yet direct comparative data are limited. We aimed to compare scan interpretation, ATTR-CM prevalence, and myocardial-to-blood pool discrimination between PYP and HMDP in real-world clinical practice. METHODS: We retrospectively analyzed 992 consecutive patients who underwent SPECT/CT for suspected ATTR-CM at a single referral center between October 2022 and January 2025. PYP was used except during two shortage periods (December 2023 to February 2024 and October 2024 to January 2025), when HMDP was substituted. Scan interpretation and final ATTR-CM diagnoses were recorded. The myocardial-to-blood-pool radiotracer uptake ratio (3D Score) was measured as a surrogate for contrast resolution. RESULTS: Of 992 unique patients (median age 76, 27% female), 816 received PYP and 176 (18%) received HMDP. Baseline clinical, echocardiographic, and biomarker characteristics were similar between groups. Rates of positive scans (PYP: 26%, HMDP: 25%; P = 0.95) and final ATTR-CM diagnoses (28% vs 26%; P = 0.59) were comparable. Among patients with positive scans (n = 256), HMDP yielded significantly higher 3D Scores (2.0 [1.7-2.5] vs 1.4 [1.2-1.7], P < 0.001), suggesting enhanced myocardial-to-blood pool contrast resolution. CONCLUSIONS: In a large cohort with similar clinical profiles, HMDP provided equivalent diagnostic yield and superior myocardial-to-blood-pool discrimination compared to PYP. These findings support HMDP as a good alternative during PYP shortages, with potential advantages in contrast resolution.
Mannan ZM, Hankinson SJ, Laychak SS
… +5 more, Hainer J, Dorbala S, Blankstein R, Di Carli MF, Divakaran S
J Nucl Cardiol
· 2026 Mar · PMID 41352577
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BACKGROUND: In suspected cardiac sarcoidosis, the interpretation of myocardial fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) can be challenging and can have important clinic...BACKGROUND: In suspected cardiac sarcoidosis, the interpretation of myocardial fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) can be challenging and can have important clinical implications. In this study, we aimed to study the prevalence of lateral wall FDG uptake in patients with suspected cardiac sarcoidosis, particularly in patients with ventricular pacing (V-pacing) or left bundle branch block (LBBB). METHODS: We retrospectively reviewed sarcoidosis-protocol FDG PET/CT studies performed at our center for clinical suspicion for cardiac sarcoidosis where an electrocardiogram (ECG) was available within three months of the PET/CT. We identified the absence or presence of LBBB or V-pacing on ECG, reviewed perfusion and FDG PET/CT findings, and classified all patients according to whether they met Heart Rhythm Society (HRS) criteria for cardiac sarcoidosis or probable cardiac sarcoidosis (meeting all HRS criteria except biopsy-proven disease and having extracardiac FDG uptake present). We also reviewed the results of cardiac magnetic resonance imaging (MRI) and follow-up FDG PET/CT imaging if applicable. Patients were followed until a composite endpoint of durable left ventricular assist device placement, cardiac transplant, or death. RESULTS: Five hundred thirty patients met inclusion criteria, 169 patients (31.9%) had V-pacing (N = 133 (78.7%)) or LBBB (N = 36 (21.3%)) on ECG, and 361 (68.1 %) had neither. Sixty-six of the 169 patients (39.1%) with V-pacing or LBBB had focal or focal-on-diffuse lateral wall myocardial FDG uptake without an associated perfusion defect, compared with 39 of the 361 patients (10.8%) without either (P < 0.001). Of the 66 patients with V-pacing/LBBB and lateral wall FDG uptake, 27 (40.9%) underwent cardiac MRI, and only six (22.2 %) had evidence of lateral wall late gadolinium enhancement (LGE). Twenty-four (36.4%) of the 66 patients had extracardiac FDG uptake, and these were the only patients with definite/probable cardiac sarcoidosis in follow-up. There was no difference in outcomes between patients with or without definite/probable cardiac sarcoidosis stratified by lateral wall myocardial FDG uptake pattern. CONCLUSIONS: Lateral wall myocardial FDG uptake without an associated perfusion defect was significantly more common among patients with LBBB or V-pacing referred for sarcoidosis FDG PET/CT imaging than among those without LBBB or V-pacing. LBBB and V-pacing should be considered as potential causes of lateral wall myocardial FDG uptake in patients with and without biopsy-proven sarcoidosis, and diagnoses other than cardiac sarcoidosis should be considered when this pattern is present but metabolically active extracardiac sarcoidosis is absent.
BACKGROUND: The application of hybrid stress single-photon emission computed tomography/computed tomography (SPECT/CT) imaging allows for the combined assessment of patients' exercise ability and coronary artery calcium...BACKGROUND: The application of hybrid stress single-photon emission computed tomography/computed tomography (SPECT/CT) imaging allows for the combined assessment of patients' exercise ability and coronary artery calcium (CAC) burden. The prognostic utility of this combined information among patients undergoing stress SPECT-myocardial perfusion imaging (MPI) remains incompletely understood. METHODS: To simulate the prognostic information that can be provided by stress SPECT/CT, we assessed 2435 patients undergoing stress SPECT-MPI and CAC scanning within six months of each other. Patients were grouped into four groups of descending stress test performance: those exercising greater than or equal to 9 minutes, exercising less than 9 minutes, undergoing pharmacologic testing while performing a walk protocol, or pharmacologic testing without walking. Patients were followed for all-cause mortality (ACM) over a mean of 9.0 ± 6.4 years. RESULTS: During follow-up, 291 patients (12.0%) died. There was a stepwise decrease in survival with poorer stress test performance and with increasing CAC scores. Mortality was consistently higher in patients with lower stress test performance among all CAC categories. Conversely, higher CAC scores were associated with increased mortality risk across all four stress test performance groups. Patients with CAC scores greater than or equal to 400 but exercising greater than or equal to 9 minutes had a mortality rate similar to patients with zero CAC scores who could not walk during pharmacologic stress testing (8.8 vs 8.0 per 1000 person-years, P = 0.898). A multivariable analysis identified stress test performance as the strongest adverse ACM predictor, followed by age and CAC scores. CONCLUSIONS: The combined assessment of stress test performance and the magnitude of CAC abnormality provides highly synergistic prognostic information among patients undergoing stress SPECT-MPI.
BACKGROUND: The longitudinal myocardial blood flow (MBF) gradient, reflecting the basal-to-apical decline in stress MBF, has been proposed as a non-invasive marker for obstructive coronary artery disease (CAD). However,...BACKGROUND: The longitudinal myocardial blood flow (MBF) gradient, reflecting the basal-to-apical decline in stress MBF, has been proposed as a non-invasive marker for obstructive coronary artery disease (CAD). However, its clinical utility in Rubidium-82 (Rb) positron emission tomography (PET) remains unestablished. METHODS: This single-center retrospective study included consecutive patients who underwent rest/dipyridamole-stress Rb PET myocardial perfusion imaging and invasive coronary angiography within 90 days from January 2012 to December 2019. Stress MBF and longitudinal gradients (basal-to-apical differences) were quantified in left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) territories. Coronary territories were stratified by coronary artery calcification (CAC) and perfusion defects (PD) into groups A (CAC-, PD-), B (CAC+, PD-), and C (PD+). Associations with CAD burden and diagnostic performance for obstructive CAD (≥50% angiographic stenosis) were evaluated using receiver operating characteristic analysis. RESULTS: Of 1,516 patients screened, 396 (median age: 68 years; 30.6% female) were included, contributing 1,077 coronary territories (LAD: 391; LCX: 377; RCA: 309). In LAD territory, longitudinal MBF gradients increased with CAD burden (P < 0.001) and improved diagnostic accuracy beyond relative perfusion and stress MBF (AUC 0.774 vs 0.743, P = 0.002). Conversely, gradients in LCX and RCA territories decreased with increasing CAD burden (both P < 0.001) and did not improve diagnostic performance (LCX: AUC 0.704 vs 0.715, P = 0.267; RCA: AUC 0.727 vs 0.723, P = 0.698). CONCLUSIONS: Longitudinal stress MBF gradients derived from Rb PET may enhance diagnostic accuracy for obstructive CAD in the LAD territory. No additional diagnostic value was observed in LCX or RCA territories.
BACKGROUND: Assessment of myocardial sympathetic innervation with iodine-123-metaiodobenzylguanidine ([I]mIBG) scintigraphy is conventionally performed by determining the heart-to-mediastinum ratio (HMR) on planar images...BACKGROUND: Assessment of myocardial sympathetic innervation with iodine-123-metaiodobenzylguanidine ([I]mIBG) scintigraphy is conventionally performed by determining the heart-to-mediastinum ratio (HMR) on planar images. This study aimed to investigate the feasibility of determining HMR from reprojected [I]mIBG planar images derived from tomographic data by a ring-configured cadmium-zinc-telluride (CZT) gamma camera and its agreement with HMR determined from [I]mIBG planar images by an Anger gamma camera, in the assessment of myocardial sympathetic innervation. METHODS: A total of 105 study participants (suspected idiopathic rapid-eye-movement sleep behavior disorder n = 55, early-stage Parkinson's Disease n = 36, and healthy controls n = 14) who were referred for [I]mIBG myocardial scintigraphy were included, in addition to eight phantom experiments simulating a range of HMR. HMR was determined from planar and reprojected planar images acquired with an Anger gamma camera and a ring-configured CZT gamma camera, respectively, for all study participants and phantom experiments. Agreement in HMR between the two imaging methods was analyzed in Bland-Altman plots. Intra- and interobserver variability was evaluated for both imaging methods in a subset of images. RESULTS: The agreement between planar and reprojected planar images was good, with a mean difference in HMR of 0.11 (95% limits of agreement -0.16 to 0.38) for the study participants. Intra- and interobserver variability was low and comparable for both imaging methods. Results from the phantom experiments were consistent with those from the study participants. CONCLUSIONS: Determining HMR from reprojected [I]mIBG myocardial scintigraphy planar images acquired with a ring-configured CZT gamma camera is feasible and shows good agreement with HMR determined from planar images by a conventional Anger gamma camera.
Miller RJ, Shanbhag A, Shahi K
… +8 more, Bosley D, Litwin L, White JA, Jimenez-Zepeda V, Dey D, Berman DS, Fine NM, Slomka PJ
J Nucl Cardiol
· 2026 Feb · PMID 41314377
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BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CM) is an increasingly recognized cause of heart failure (HF) in older adults. Several therapies for ATTR-CM are now available, with more currently in development. As s...BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CM) is an increasingly recognized cause of heart failure (HF) in older adults. Several therapies for ATTR-CM are now available, with more currently in development. As such, there is an increasing need for methods to assess response to therapy. We evaluated the associations between serial 99m-technetium pyrophosphate (Tc-PYP) deep learning measurements with changes in other imaging parameters and clinical outcomes. METHODS: We included patients with a diagnosis of ATTR-CM and at least two Tc-PYP studies followed through the Amyloidosis Program of Calgary. Patients underwent laboratory testing, echocardiography, and cardiovascular magnetic resonance unless contraindications were present. Tc-PYP images were quantified using our previously developed deep learning methodology including assessment of cardiac pyrophosphate activity (CPA) and volume of involvement (VOI). RESULTS: In total, 85 patients were included, with a median population age of 79 years (interquartile range [IQR]: 72 - 84) and 76 (89%) male patients. In patients on therapy, there was a reduction in VOI (median: 100 to 51, P < 0.001), CPA (median: 165 to 81, P < 0.001), native T1 (median: 1400 to 1387, P = 0.005), and extracellular volume (median: 50 to 49, P = 0.035) during a median time of 369 days (IQR: 365-516) between scans. There was a modest correlation between change in CPA and change in native T1 (ρ = 0.376, P = 0.009). After adjusting for age, treatment, and CPA at follow-up, an increase in CPA during follow-up was also associated with an increased risk (adjusted hazard ratio: 2.31 per standard deviation increase, 95% confidence interval: 1.28-4.17, P = 0.005). CONCLUSIONS: Serial Tc-PYP quantitation has modest correlations with other measures of disease burden including native T1. Changes in these measures were associated with risk of cardiovascular death or HF hospitalization, suggesting that the serial measurements may be clinically meaningful surrogate endpoints.
BACKGROUND: The novel perfusion single photon emission computed tomography (SPECT) tracer Tc-4BOH shows potential for accurate myocardial blood flow (MBF) quantification. This study aimed to determine the optimal pharmac...BACKGROUND: The novel perfusion single photon emission computed tomography (SPECT) tracer Tc-4BOH shows potential for accurate myocardial blood flow (MBF) quantification. This study aimed to determine the optimal pharmacokinetic model and dynamic acquisition protocol for Tc-4BOH in coronary artery disease patients. METHODS: Sixty patients underwent 10-minute rest and stress dynamic Tc-4BOH SPECT scans. One-tissue (1T), reversible two-tissue (2T), and irreversible two-tissue (2Ti) compartment models applied to myocardial time-activity curves using image-derived input functions. Model selection relied on the K agreement with N-NH MBF in 8 patients and on the reliability of K across all 60 patients. The optimal acquisition time was further investigated by K reliability and its correlation with 10-minute results. Regional analyses were performed on 3 coronary territories and 17 American Heart Association (AHA) segments. RESULTS: The 1T model provided stable and reliable K estimates for 10-, 8-, 6-, and 4-minute scans, with consistent bias and standard deviation relative to N-NH MBF. Across all 60 patients, 1T outperformed 2T and 2Ti, showing the lowest relative standard error and fewest unreliable estimates, resulting in a rest K of 0.72 ± 0.18 mL/g/min and a stress K of 1.62 ± 0.35 mL/g/min using the 10-minute scan. Strong correlations (r > 0.9, P < 0.001) were observed between K from shortened (8, 6, 4 minutes) and 10-minute scans but decreased at 2 minutes. Regional analyses confirmed that 4-minute scans with 1T yielded reliable K quantification (r > 0.9, P < 0.001). CONCLUSION: The 1T model is optimal for dynamic Tc-4BOH SPECT and a 4-min scan is sufficient for reliable global and regional MBF quantification.
BACKGROUND: This study aimed to investigate the relationship between pressure overload-induced right ventricular (RV) fibrotic remodeling detected by Tc-fibroblast activation protein inhibitor (FAPI) single photon emissi...BACKGROUND: This study aimed to investigate the relationship between pressure overload-induced right ventricular (RV) fibrotic remodeling detected by Tc-fibroblast activation protein inhibitor (FAPI) single photon emission computed tomography/computed tomography (SPECT/CT) and echocardiographic biomechanical adaptation/maladaptation in chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Thirty-seven CTEPH patients scheduled for balloon pulmonary angiography (BPA) underwent baseline Tc-FAPI SPECT/CT, speckle-tracking echocardiography (measuring RV global strain [GS] and free-wall strain [FWS]), and right heart catheterization. Baseline RV FAPI uptake (peak myocardial-to-blood ratio, TBR) was compared with RV strain and RV-pulmonary artery coupling parameters. Twenty patients received repeated BPA sessions, and a subgroup of 10 underwent repeat FAPI SPECT and strain analysis after a single BPA. RESULTS: Baseline global RV FAPI TBR varied among CTEPH patients (mean ± SD: 2.92 ± 0.96; range: 1.44-4.76). Patients without RV uptake exhibited significantly higher strain values and preserved RV-pulmonary artery coupling compared to those with uptake. TBR of free wall correlated positively with RVGS (r = 0.450, P = 0.005), RVGS/sPAP (global right ventricular longitudinal strain/systolic pulmonary artery pressure) (r = 0.370, P = 0.024), right ventricular free-wall longitudinal strain (RVFWS, r = 0.386, P = 0.018), and RVFWS/sPAP (r = 0.347, P = 0.035). Following a single BPA, RV FAPI uptake decreased in 6 of 10 patients and increased modestly in 4. Changes in FAPI uptake (global ΔTBR) significantly correlated with ΔRVGS (r = 0.697, P = 0.025), ΔRVFWS (r = 0.710, P = 0.022), ΔRVGS/sPAP (r = 0.694, P = 0.026), ΔRVFWS/sPAP (r = 0.700, P = 0.024). CONCLUSION: In CTEPH, RV fibrotic remodeling quantified by FAPI SPECT/CT correlated with echocardiographic RV strain and ventricular-pulmonary artery coupling. Following BPA, changes in RV FAPI uptake appeared dynamic, with fluctuations potentially corresponding to alterations in both RV strain and ventricular-pulmonary coupling parameters.