Journal: J Nucl Cardiol

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Abstract

Predictive values of left ventricular mechanical dyssynchrony for CRT response in heart failure patients with different pathophysiology.

He Z, Li D, Cui C, Qin HY, ... Wang C, Zhou W
Background
Cardiac resynchronization therapy (CRT) patients with different pathophysiology may influence mechanical dyssynchrony and get different ventricular resynchronization and clinical outcomes.
Methods
Ninety-two dilated cardiomyopathy (DCM) and fifty ischemic cardiomyopathy (ICM) patients with gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) were included in this retrospective study. Patients were classified based on the concordance between the left ventricular (LV) lead and the latest contraction or relaxation position. If the LV lead was located on or adjacent to both the latest contraction and relaxation position, the patient was categorized into the both match group; if the LV lead was located on or adjacent to the latest contraction or relaxation position, the patient was classified into the one match group; if the LV lead was located on or adjacent to neither the latest contraction nor relaxation position, the patient was categorized to the neither group. CRT response was defined as [Formula: see text] improvement of LV ejection fraction at the 6-month follow-up. Variables with P < .05 in the univariate analysis were included in the stepwise multivariate model.
Results
During the follow-up period, 58.7% (54 of 92) for DCM patients and 54% (27 of 50) for ICM patients were CRT responders. The univariate analysis and stepwise multivariate analysis showed that QRS duration, systolic phase bandwidth (PBW), diastolic PBW, diastolic phase histogram standard deviation (PSD), and left ventricular mechanical dyssynchrony (LVMD) concordance were independent predictors of CRT response in DCM patients; diabetes mellitus and left ventricular end-systolic volume were significantly associated with CRT response in ICM patients. The intra-group comparison revealed that the CRT response rate was significantly different in the both match group of DCM (N = 18, 94%) and ICM (N = 24, 62%) patients (P = .016). However, there was no significant difference between DCM and ICM in the one match and neither group. For the inter-group comparison, Kruskal-Wallis H-test revealed that CRT response was significantly different in all the groups of DCM patients (P < .001), but not in ICM patients (P = .383).
Conclusions
Compared with ICM patients, systolic PBW, diastolic PBW and PSD have better predictive and prognostic values for the CRT response in DCM patients. Placing the LV lead in or adjacent to the latest contraction and relaxation position can improve the clinical outcomes of DCM patients, but it does not apply to ICM patients.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 16 Sep 2021; epub ahead of print
He Z, Li D, Cui C, Qin HY, ... Wang C, Zhou W
J Nucl Cardiol: 16 Sep 2021; epub ahead of print | PMID: 34535872
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Abstract

Effect of changes in perfusion defect size during serial stress myocardial perfusion imaging on cardiovascular outcomes in patients treated with primary percutaneous coronary intervention after myocardial infarction.

Zampella E, Mannarino T, Gaudieri V, D\'Antonio A, ... Cuocolo A, Acampa W
Background
We evaluated the prognostic value of changes in perfusion defect size (PDS) on serial MPS in patients treated with primary percutaneous coronary intervention (PCI) after acute myocardial infarction (AMI).
Methods
We enrolled 112 patients treated with primary PCI after AMI who underwent two stress MPS within 1 month and after 6 months. Improvement in PDS was defined as a reduction ≥5%. Remodeling was defined as an increase in left ventricular (LV) end-diastolic volume index ≥20%. Cardiac events included cardiac death, nonfatal MI, unstable angina, repeated revascularization, and heart failure.
Results
During a median follow-up of 86 months, 22 events occurred. Event rate was higher (P < .01) in patients with worsening of PDS compared to those with unchanged or improved PDS. Moreover, patients with remodeling had a higher (P < .001) event rate compared to those without. At Cox analysis, worsening of PDS and remodeling resulted independent predictors of events (both P < .01). Patients with both worsening of PDS and remodeling had the worst event-free survival (P <.001).
Conclusion
In patients treated with primary PCI after AMI, worsening of PDS and remodeling are associated to higher risk of events at long-term follow-up. Gated stress MPS improves risk stratification in these patients.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 12 Sep 2021; epub ahead of print
Zampella E, Mannarino T, Gaudieri V, D'Antonio A, ... Cuocolo A, Acampa W
J Nucl Cardiol: 12 Sep 2021; epub ahead of print | PMID: 34519009
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Abstract

[F]FDG and [F]NaF as PET markers of systemic atherosclerosis progression: A longitudinal descriptive imaging study in patients with type 2 diabetes mellitus.

Reijrink M, de Boer SA, Te Velde-Keyzer CA, Sluiter JKE, ... Mulder DJ, Slart RHJA
Background
While [18F]-fluordeoxyglucose ([18F]FDG) uptake is associated with arterial inflammation, [18F]-sodium fluoride ([18F]NaF) is a marker for arterial micro-calcification. We aimed to investigate the prospective correlation between both PET markers over time and whether they are prospectively ([18F]FDG) and retrospectively ([18F]NaF) related to progression of systemic arterial disease in a longitudinal study in patients with type 2 diabetes mellitus (T2DM).
Methods
Baseline [18F]FDG PET/Low Dose (LD) Computed Tomography (CT) scans of ten patients with early T2DM without cardiovascular history (70% men, median age 63 years) were compared with five-year follow-up [18F]NaF/LDCT scans. Systemic activity was expressed as mean target-to-background ratio (meanTBR) by dividing the maximal standardized uptake value (SUVmax) of ten arteries by SUVmean of the caval vein. CT-assessed macro-calcifications were scored visually and expressed as calcified plaque (CP) score. Arterial stiffness was assessed with carotid-femoral pulse wave velocity (PWV). Five-year changes were expressed absolutely with delta (Δ) and relatively with %change.
Results
Baseline meanTBR[18F]FDG was strongly correlated with five-year follow-up meanTBR[18F]NaF (r = 0.709, P = .022). meanTBR[18F]NaF correlated positively with ΔCPscore, CPscore at baseline, and follow-up (r = 0.845, P = .002 and r = 0.855, P = .002, respectively), but not with %change in CPscore and PWV.
Conclusion
This proof-of-concept study demonstrated that systemic arterial inflammation is an important pathogenetic factor in systemic arterial micro-calcification development.

© 2021. The Author(s).

J Nucl Cardiol: 12 Sep 2021; epub ahead of print
Reijrink M, de Boer SA, Te Velde-Keyzer CA, Sluiter JKE, ... Mulder DJ, Slart RHJA
J Nucl Cardiol: 12 Sep 2021; epub ahead of print | PMID: 34519008
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Abstract

The prognostic value of positron emission tomography in the evaluation of suspected cardiac sarcoidosis.

Patel VN, Pieper JA, Poitrasson-Rivière A, Kopin D, ... Murthy VL, Koelling T
Objectives
To assess the prognostic value of positron emission tomography (PET) imaging in patients undergoing evaluation for known or suspected cardiac sarcoidosis (CS) while not on active immunotherapy.
Background
Previous studies have attempted to identify the value of PET imaging to aid in risk stratification of patients with CS, however, most cohorts have included patients currently on immunosuppression, which may confound scan results by suppressing positive findings.
Methods
We retrospectively analyzed 197 patients not on immunosuppression who underwent 18F-fluorodeoxyglucose (FDG) PET scans for evaluation of known or suspected CS. The primary endpoint of the study was time to ventricular arrhythmia (VT/VF), or death. Candidate predictors were identified by univariable Cox proportional hazards regression. Independent predictors were identified by performing multivariable Cox regression with stepwise forward selection.
Results
Median follow-up time was 531 [IQR 309, 748] days. 41 patients met the primary endpoint. After stepwise forward selection, left ventricular ejection fraction (LVEF) (HR 0.98, 95% CI 0.96-0.99, P = 0.02), history of VT/VF (HR 4.19, 95% CI 2.15-8.17, P < 0.001), and summed rest score (SRS) (HR 1.06, 95% CI 1.02-1.12, P = 0.01) were predictive of the primary endpoint. Quantitative and qualitative measures of FDG uptake on PET were not predictive of clinical events.
Conclusions
Among untreated patients who underwent PET scans to evaluate known or suspected CS, LVEF, history of VT/VF, and SRS were associated with adverse clinical outcomes.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 08 Sep 2021; epub ahead of print
Patel VN, Pieper JA, Poitrasson-Rivière A, Kopin D, ... Murthy VL, Koelling T
J Nucl Cardiol: 08 Sep 2021; epub ahead of print | PMID: 34505261
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Abstract

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

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

© 2021. The Author(s).

J Nucl Cardiol: 02 Sep 2021; epub ahead of print
Wang R, Li X, Huangfu S, Yao Q, ... Yan R, Li S
J Nucl Cardiol: 02 Sep 2021; epub ahead of print | PMID: 34476781
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Abstract

Effect of respiratory motion correction and CT-based attenuation correction on dual-gated cardiac PET image quality and quantification.

Schultz J, Siekkinen R, Tadi MJ, Teräs M, ... Saraste A, Teuho J
Background
Dual-gating reduces respiratory and cardiac motion effects but increases noise. With motion correction, motion is minimized and image quality preserved. We applied motion correction to create end-diastolic respiratory motion corrected images from dual-gated images.
Methods
[18F]-fluorodeoxyglucose ([18F]-FDG) PET images of 13 subjects were reconstructed with 4 methods: non-gated, dual-gated, motion corrected, and motion corrected with 4D-CT (MoCo-4D). Image quality was evaluated using standardized uptake values, contrast ratio, signal-to-noise ratio, coefficient of variation, and contrast-to-noise ratio. Motion minimization was evaluated using myocardial wall thickness.
Results
MoCo-4D showed improvement for contrast ratio (2.83 vs 2.76), signal-to-noise ratio (27.5 vs 20.3) and contrast-to-noise ratio (14.5 vs 11.1) compared to dual-gating. The uptake difference between MoCo-4D and non-gated images was non-significant (P > .05) for the myocardium (2.06 vs 2.15 g/mL), but significant (P < .05) for the blood pool (.80 vs .86 g/mL). Non-gated images had the lowest coefficient of variation (27.3%), with significant increase for all other methods (31.6-32.5%). MoCo-4D showed smallest myocardial wall thickness (16.6 mm) with significant decrease compared to non-gated images (20.9 mm).
Conclusions
End-diastolic respiratory motion correction and 4D-CT resulted in improved motion minimization and image quality over standard dual-gating.

© 2021. The Author(s).

J Nucl Cardiol: 02 Sep 2021; epub ahead of print
Schultz J, Siekkinen R, Tadi MJ, Teräs M, ... Saraste A, Teuho J
J Nucl Cardiol: 02 Sep 2021; epub ahead of print | PMID: 34476780
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Abstract

Added value of coronary artery calcium score in the reporting of SPECT versus PET myocardial perfusion imaging.

Mouden M, Jager PL, van Dalen JA, van Dijk JD
Background
Knowledge of coronary artery calcium score (CACS) influences the interpretation of myocardial perfusion imaging (MPI) with SPECT; however, the impact on PET interpretation remains unclear. We compared the added value of CACS to reporting MPI using SPECT vs PET.
Methods
We retrospectively included 412 patients. 206 patients who underwent Rb-82 PET were propensity-based matched to a cohort of 4018 patients who underwent cadmium-zinc-telluride SPECT MPI to obtain a comparable group of 206 SPECT patients. Next, we created four image sets: SPECT MPI-only, PET-only, SPECT + CACS, and PET + CACS. Two physicians interpreted the 824 images as normal, equivocal, or abnormal for ischemia or irreversible defects. Additionally, event rates were compared between PET and SPECT groups during 30-month follow-up.
Results
PET yielded more scans interpreted as normal than SPECT (88% vs 80%, respectively, P = 0.015). Adding CACS to SPECT increased the percentage of normal scans to 86% (P = 0.014), whereas this effect was absent for PET (90%, P = 0.77). Annualized event rates for images interpreted as normal did not differ and varied between 0.7 and 2.0% (P > 0.084).
Conclusion
Adding CACS correctly increased the percentage of normal scans for SPECT MPI but not for PET, possibly limiting the effect of adding CACS to reporting PET.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 02 Sep 2021; epub ahead of print
Mouden M, Jager PL, van Dalen JA, van Dijk JD
J Nucl Cardiol: 02 Sep 2021; epub ahead of print | PMID: 34476779
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Abstract

Multimodality imaging to distinguish between benign and malignant cardiac masses.

Aghayev A, Cheezum MK, Steigner ML, Mousavi N, ... Di Carli MF, Blankstein R
Background
To compare the diagnostic accuracy of CMR and FDG-PET/CT and their complementary role to distinguish benign vs malignant cardiac masses.
Methods
Retrospectively assessed patients with cardiac mass who underwent CMR and FDG-PET/CT within a month between 2003 and 2018.
Results
72 patients who had CMR and FDG-PET/CT were included. 25 patients (35%) were diagnosed with benign and 47 (65%) were diagnosed with malignant masses. 56 patients had histological correlation: 9 benign and 47 malignant masses. CMR and FDG-PET/CT had a high accuracy in differentiating benign vs malignant masses, with the presence of CMR features demonstrating a higher sensitivity (98%), while FDG uptake with SUVmax/blood pool ≥ 3.0 demonstrating a high specificity (88%). Combining multiple (> 4) CMR features and FDG uptake (SUVmax/blood pool ratio ≥ 3.0) yielded a sensitivity of 85% and specificity of 88% to diagnose malignant masses. Over a mean follow-up of 2.6 years (IQR 0.3-3.8 years), risk-adjusted mortality were highest among patients with an infiltrative border on CMR (adjusted HR 3.1; 95% CI 1.5-6.5; P = .002) or focal extracardiac FDG uptake (adjusted HR 3.8; 95% CI 1.9-7.7; P < .001).
Conclusion
Although CMR and FDG-PET/CT can independently diagnose benign and malignant masses, the combination of these modalities provides complementary value in select cases.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 01 Sep 2021; epub ahead of print
Aghayev A, Cheezum MK, Steigner ML, Mousavi N, ... Di Carli MF, Blankstein R
J Nucl Cardiol: 01 Sep 2021; epub ahead of print | PMID: 34476778
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Abstract

Efficacy and safety of cardiac shock wave therapy for patients with severe coronary artery disease: A randomized, double-blind control study.

Jia N, Zhang R, Liu B, Liu B, ... Yao Z, He Q
Background
Previous studies proved the efficacy of cardiac shock wave therapy (CSWT) for coronary artery disease (CAD) patients who are not candidate for reperfusion therapy. Randomized control trials are limited. We try to explore the efficacy and safety of CSWT for patients with severe CAD.
Methods
Thirty patients with severe CAD who had obvious ischemia on myocardial perfusion imaging (MPI) were enrolled and randomly assigned to the CSWT group or the control group. They had received optimal medication treatment for at least three months. Nine sessions of shock wave therapy were conducted over 3 months. CSWT group received the real treatment, while the control group received the pseudo-treatment. Clinical symptom, imaging outcomes and safety parameters were compared between two groups.
Results
After treatment, regional stress score (P = .023), improvement rate (IR) of ischemic area (IA) stress (P < .001) and IR of IA difference (P < .001) were significantly favor CSWT group. The interaction of summed rest score (P < .001), summed stress score (P = .004), summed difference score (P = .036) were significantly improved in the CSWT group compared to the control group. Seattle angina questionnaire, quality of life (QOL) and the distance of six-minute walking test (6MWT) were improved in both groups without significant difference between them. Hemodynamic parameters were stable during procedure. Myocardial injury markers showed no changes in two groups.
Conclusions
Our study demonstrated CSWT could effectively and safely improve myocardial perfusion in patients with severe CAD. Clinical symptom, QOL and 6MWT were all improved after treatment, but no significant difference between two groups.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 01 Sep 2021; epub ahead of print
Jia N, Zhang R, Liu B, Liu B, ... Yao Z, He Q
J Nucl Cardiol: 01 Sep 2021; epub ahead of print | PMID: 34476776
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Abstract

Effect of iterations and time of flight on normal distributions of Rb PET relative perfusion and myocardial blood flow.

Poitrasson-Rivière A, Moody JB, Renaud JM, Hagio T, ... Murthy VL, Ficaro EP
Background
As clinical use of myocardial blood flow (MBF) increases, dynamic series are becoming part of the typical workflow. The methods and parameters used to reconstruct these series require investigation to ensure accurate quantification.
Methods
Fifty-nine rest/stress dynamic 82Rb PET studies, acquired on a Biograph mCT, from a combination of normal volunteers and low-likelihood patients were reconstructed with and without time of flight (TOF) for varying iterations and processed to obtain relative perfusion and MBF polar maps. Regional values from mean polar maps were fit to a linear mixed-effect model to quantify convergence and select the optimal number of iterations.
Results
TOF reconstructions converged faster and yielded more uniform relative perfusion polar maps. However, the stress MBF distribution for TOF reconstructions was more heterogeneous, with a higher-intensity septal wall. This phenomenon requires further investigation, with right ventricle blood pool spillover possibly having an effect. Optimal reconstructions were defined as 5-iteration non-TOF (24-subset) reconstructions and 3-iteration TOF (21-subset) reconstructions.
Conclusion
Optimal cardiac reconstructions were identified for non-TOF and TOF reconstructions of dynamic series. TOF reconstruction presents as the more accurate method, given the more uniform relative perfusion distribution.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 25 Aug 2021; epub ahead of print
Poitrasson-Rivière A, Moody JB, Renaud JM, Hagio T, ... Murthy VL, Ficaro EP
J Nucl Cardiol: 25 Aug 2021; epub ahead of print | PMID: 34448094
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Abstract

Serial changes of myocardial perfusion imaging in takotsubo and reverse takotsubo cardiomyopathy.

Miyajima K, Tawarahara K, Saito N
Background
Takotsubo cardiomyopathy (TTC) shows reversible hypokinesis in the left ventricular (LV) apical-half segment and hyperkinesis in the LV basal-half segment. However, the precise pathophysiological mechanism of TTC is unclear. Therefore, this study sought to clarify the nuclear characteristics, degree of myocardial damage, and serial change of TTC and rTTC using myocardial perfusion imaging.
Methods
We performed myocardial perfusion scintigraphy in 28 patients (TTC: 20, rTTC: 8) using Tc-99m sestamibi and assessed minimum percentage uptake (min-%-uptake), extent score (ES) and summed rest score (SRS) at acute and chronic phases.
Results
Min-%-uptake improved from the acute to the chronic phase (TTC: 54 [48-59]% vs 87 [81-90]%, P  < 0.01; rTTC: 60 [55-64]% vs 77 [71-79]%, P < 0.01), as did the ES (TTC: 32 [26-41]% vs 0.0 [0.0-6.0]%, P < 0.01; rTTC: 16 [12-34]% vs 0.0 [0.0-0.0]%, P = 0.02) and SRS (TTC: 4.5 [3.9-5.3] vs 0.0 [0.0-0.2], P < 0.01; rTTC: 3.6 [3.3-3.8] vs 0.0 [0.0-0.0], P = 0.01).
Conclusion
Tc-99m sestamibi uptake was reduced in hypokinetic regions in the acute phase and improved in the chronic phase. TTC and rTTC may involve a reversible disorder of the myocardial cell membrane, mitochondria, and microcirculation.

© 2021. The Author(s).

J Nucl Cardiol: 23 Aug 2021; epub ahead of print
Miyajima K, Tawarahara K, Saito N
J Nucl Cardiol: 23 Aug 2021; epub ahead of print | PMID: 34427859
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Abstract

Myocardial flow reserve estimation with contemporary CZT-SPECT and Tc-tracers lacks precision for routine clinical application.

Renaud JM, Poitrasson-Rivière A, Hagio T, Moody JB, ... Ficaro EP, Murthy VL
Background
PET myocardial flow reserve (MFR) has established diagnostic and prognostic value. Technological advances have now enabled SPECT MFR quantification. We investigated whether SPECT MFR precision is sufficient for clinical categorization of patients.
Methods
Validation studies vs invasive flow measurements and PET MFR were reviewed to determine global SPECT MFR thresholds. Studies vs PET and a SPECT MFR repeatability study were used to establish imprecision in SPECT MFR measurements as the standard deviation of the difference between SPECT and PET MFR, or test-retest SPECT MFR. Simulations were used to evaluate the impact of SPECT MFR imprecision on confidence of clinically relevant categorization.
Results
Based on validation studies, the typical PET MFR categories were used for SPECT MFR classification (< 1.5, 1.5-2.0, > 2.0). Imprecision vs PET MFR ranged from 0.556 to 0.829, and test-retest imprecision was 0.781-0.878. Simulations showed correct classification of up to only 34% of patients when 1.5 ≤ true MFR ≤ 2.0. Categorization with high confidence (> 80%) was only achieved for extreme MFR values (< 1.0 or > 2.5), with correct classification in only 15% of patients in a typical lab with MFR of 1.8 ± 0.5.
Conclusions
Current SPECT-derived estimates of MFR lack precision and require further optimization for clinical risk stratification.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 22 Aug 2021; epub ahead of print
Renaud JM, Poitrasson-Rivière A, Hagio T, Moody JB, ... Ficaro EP, Murthy VL
J Nucl Cardiol: 22 Aug 2021; epub ahead of print | PMID: 34426935
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Impact:
Abstract

Clinical implications of compromised Rb PET data acquisition.

Van Tosh A, Cao JJ, Votaw JR, Cooke CD, Palestro CJ, Nichols KJ
Background
We wished to document the prevalence and quantitative effects of compromised 82Rb PET data acquisitions on myocardial flow reserve (MFR).
Methods and results
Data were analyzed retrospectively for 246 rest and regadenoson-stress studies of 123 patients evaluated for known or suspected CAD. An automated injector delivered pre-determined activities of 82Rb. Automated quality assurance algorithms identified technical problems for 7% (9/123) of patients. Stress data exhibited 2 instances of scanner saturation, 1 blood peak detection, 1 blood peak width, 1 gradual patient motion, and 2 abrupt patient motion problems. Rest data showed 1 instance of blood peak width and 2 abrupt patient motion problems. MFR was lower for patients with technical problems flagged by the quality assurance algorithms than those without technical problems (1.5 ± 0.5 versus 2.1 ± 0.7, P = 0.01), even though rest and stress ejection fraction, asynchrony and relative myocardial perfusion measures were similar for these two groups (P > 0.05), suggesting that MFR accuracy was adversely affected by technical errors.
Conclusion
It is important to verify integrity of 82Rb data to ensure MFR computation quality.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 19 Aug 2021; epub ahead of print
Van Tosh A, Cao JJ, Votaw JR, Cooke CD, Palestro CJ, Nichols KJ
J Nucl Cardiol: 19 Aug 2021; epub ahead of print | PMID: 34417670
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Abstract

Prognostic value of myocardial flow reserve obtained by 82-rubidium positron emission tomography in long-term follow-up after heart transplantation.

Nelson LM, Christensen TE, Rossing K, Hasbak P, Gustafsson F
Background
Cardiac allograft vasculopathy (CAV) is a leading cause of death following heart transplantation (HTx) and non-invasive prognostic methods in long-term CAV surveillance are needed. We evaluated the prognostic value of myocardial flow reserve (MFR) obtained by 82-rubidium (82Rb) positron emission tomography (PET).
Methods
Recipients undergoing dynamic rest-stress 82Rb PET between April 2013 and June 2017 were retrospectively evaluated in a single-center study. Evaluation by PET included quantitative myocardial blood flow and semiquantitative myocardial perfusion imaging. Patients were grouped by MFR (MFR ≤ 2.0 vs MFR > 2.0) and the primary outcome was all-cause mortality.
Results
A total of 50 patients (68% men, median age 57 [IQR: 43 to 68]) were included. Median time from HTx to PET was 10.0 (6.7 to 16.0) years. In 58% of patients CAV was documented prior to PET. During a median follow-up of 3.6 (2.3 to 4.3) years 12 events occurred. Survival probability by Kaplan-Meier method was significantly higher in the high-MFR group (log-rank P = .02). Revascularization (n = 1), new CAV diagnosis (n = 1), and graft failure (n = 4) were more frequent in low-MFR patients. No retransplantation occurred.
Conclusions
Myocardial flow reserve appears to offer prognostic value in selected long-term HTx recipients and holds promise as a non-invasive method for CAV surveillance possibly guiding management strategy.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 18 Aug 2021; epub ahead of print
Nelson LM, Christensen TE, Rossing K, Hasbak P, Gustafsson F
J Nucl Cardiol: 18 Aug 2021; epub ahead of print | PMID: 34414554
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Abstract

Clinical impacts of scar reduction on gated myocardial perfusion SPECT after cardiac resynchronization therapy.

Wang CY, Hung GU, Lo HC, Tsai SC, ... Huang JL, Chen SA
Background
It had not been reported that myocardial scar shown on gated myocardial perfusion SPECT (GMPS) might reduce after cardiac resynchronization therapy (CRT). In this study, we aim to investigate the clinical impact and characteristic of scar reduction (SR) after CRT.
Methods and results
Sixty-one heart failure patients following standard indication for CRT received twice GMPS as pre- and post-CRT evaluations. The patients with an absolute reduction of scar ≥ 10% after CRT were classified as the SR group while the rest were classified as the non-SR group. The SR group (N = 22, 36%) showed more improvement on LV function (∆LVEF: 18.1 ± 12.4 vs 9.4 ± 9.9 %, P = 0.007, ∆ESV: - 91.6 ± 52.6 vs - 38.1 ± 46.5 mL, P < 0.001) and dyssynchrony (ΔPSD: - 26.19 ± 18.42 vs - 5.8 ± 23.0°, P < 0.001, Δ BW: - 128.7 ± 82.8 vs - 25.2 ± 109.0°, P < 0.001) than non-SR group (N = 39, 64%). Multivariate logistic regression analysis showed baseline QRSd (95% CI 1.019-1.100, P = 0.006) and pre-CRT Reduced Wall Thickening (RWT) (95% CI 1.016-1.173, P = 0.028) were independent predictors for the development of SR.
Conclusion
More than one third of patients showed SR after CRT who had more post-CRT improvement on LV function and dyssynchrony than those without SR. Wider QRSd and higher RWT before CRT were related to the development of SR after CRT.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 18 Aug 2021; epub ahead of print
Wang CY, Hung GU, Lo HC, Tsai SC, ... Huang JL, Chen SA
J Nucl Cardiol: 18 Aug 2021; epub ahead of print | PMID: 34414552
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Abstract

One-tissue compartment model for myocardial perfusion quantification with N-13 ammonia PET provides matching results: A cross-comparison between Carimas, FlowQuant, and PMOD.

Nesterov SV, Sciagrà R, Orozco LEJ, Prior JO, ... Gwet KL, Knuuti JM
Purpose
To cross-compare three software packages (SPs)-Carimas, FlowQuant, and PMOD-to quantify myocardial perfusion at global, regional, and segmental levels.
Materials and methods
Stress N-13 ammonia PET scans of 48 patients with HCM were analyzed in three centers using Carimas, FlowQuant, and PMOD. Values agreed if they had an ICC > 0.75 and a difference < 20% of the median across all observers.
Results
When using 1TCM on the global level, the agreement was good, and the maximum difference between 1TCM MBF values was 17.2% (ICC = 0.83). On the regional level, the agreement was acceptable except in the LCx region (25.5% difference, ICC = 0.74) between FlowQuant and PMOD. Carimas-1TCM agreed well with PMOD-1TCM and FlowQuant-1TCM. Values obtained with FlowQuant-1TCM had a somewhat lesser agreement with PMOD-1TCM, especially at the segmental level.
Conclusions
The global and regional MBF values (with one exception) agree well between the different software packages. There is significant variability in segmental values, mainly located in the LCx region and segments. Out of the studied tools, Carimas can be used interchangeably with both PMOD and FlowQuant for 1TCM implementation on all levels-global, regional, and segmental.

© 2021. The Author(s).

J Nucl Cardiol: 17 Aug 2021; epub ahead of print
Nesterov SV, Sciagrà R, Orozco LEJ, Prior JO, ... Gwet KL, Knuuti JM
J Nucl Cardiol: 17 Aug 2021; epub ahead of print | PMID: 34409572
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Impact:
Abstract

Left ventricular ejection fraction, myocardial blood flow and hemodynamic variables in adenosine and regadenoson vasodilator 82-Rubidium PET.

Frey SM, Honegger U, Clerc OF, Caobelli F, Haaf P, Zellweger MJ
Aims
In most Rubidium-(Rb)-positron emission tomography (PET) studies, dipyridamole was used as vasodilator. The aim was to evaluate vasodilator PET left ventricular ejection fraction (LVEF), myocardial blood flow (MBF), hemodynamics, and the influence of adenosine and regadenoson on these variables.
Methods and results
Consecutive patients (N = 2299) with prior coronary artery disease (CAD) or no prior CAD undergoing adenosine/regadenoson 82Rb-PET were studied and compared according to CAD status and normal/abnormal PET (summed stress score 0-3 vs. ≥4). Rest and stress LVEF differed significantly depending on CAD status and scan results. In patients with no prior CAD, rest/stress LVEF were 68% and 72%, in patients with prior CAD 60% and 63%. LVEF during stress increased 5 ± 6% in normal compared to 1 ± 8% in abnormal PET (P<0.001). Global rest myocardial blood flow(rMBF), stress MBF(sMBF) and myocardial flow reserve (sMBF/rMBF) were significantly higher in no prior CAD patients compared to prior CAD patients(1.3 ± 0.5, 3.3 ± 0.9, 2.6 ± 0.8 and 1.2 ± 0.4, 2.6 ± 0.8, 2.4 ± 0.8 ml/g/min, respectively, P<0.001) and in normal versus abnormal scans, irrespective of CAD status(no prior CAD: 1.4 ± 0.5, 3.5 ± 0.8, 2.8 ± 0.8 and 1.2 ± 0.8, 2.5 ± 0.8, 2.2 ± 0.7; prior CAD: 1.3 ± 0.4, 3.1 ± 0.8, 2.7 ± 0.8 and 1.1 ± 0.4, 2.3 ± 0.7, 2.2 ± 0.7 ml/g/min, respectively, P<0.001). LVEF and hemodynamic values were similar for adenosine and regadenoson stress. Stress LVEF ≥70% excluded relevant ischemia (≥10%) with a negative predictive value (NPV) of 94% (CI 92-95%).
Conclusions
Rest/stress LVEF, LVEF reserve and MBF values are lower in abnormal compared to normal scans. Adenosine and regadenoson seem to have similar effect on stress LVEF, MBF and hemodynamics. A stress LVEF ≥70% has a high NPV to exclude relevant ischemia.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 12 Aug 2021; epub ahead of print
Frey SM, Honegger U, Clerc OF, Caobelli F, Haaf P, Zellweger MJ
J Nucl Cardiol: 12 Aug 2021; epub ahead of print | PMID: 34386864
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Impact:
Abstract

\"Global\" cardiac atherosclerotic burden assessed by artificial intelligence-based versus manual segmentation in F-sodium fluoride PET/CT scans: Head-to-head comparison.

Piri R, Edenbrandt L, Larsson M, Enqvist O, ... Gerke O, Høilund-Carlsen PF
Background
Artificial intelligence (AI) is known to provide effective means to accelerate and facilitate clinical and research processes. So in this study it was aimed to compare a AI-based method for cardiac segmentation in positron emission tomography/computed tomography (PET/CT) scans with manual segmentation to assess global cardiac atherosclerosis burden.
Methods
A trained convolutional neural network (CNN) was used for cardiac segmentation in 18F-sodium fluoride PET/CT scans of 29 healthy volunteers and 20 angina pectoris patients and compared with manual segmentation. Parameters for segmented volume (Vol) and mean, maximal, and total standardized uptake values (SUVmean, SUVmax, SUVtotal) were analyzed by Bland-Altman Limits of Agreement. Repeatability with AI-based assessment of the same scans is 100%. Repeatability (same conditions, same operator) and reproducibility (same conditions, two different operators) of manual segmentation was examined by re-segmentation in 25 randomly selected scans.
Results
Mean (± SD) values with manual vs. CNN-based segmentation were Vol 617.65 ± 154.99 mL vs 625.26 ± 153.55 mL (P = .21), SUVmean 0.69 ± 0.15 vs 0.69 ± 0.15 (P = .26), SUVmax 2.68 ± 0.86 vs 2.77 ± 1.05 (P = .34), and SUVtotal 425.51 ± 138.93 vs 427.91 ± 132.68 (P = .62). Limits of agreement were - 89.42 to 74.2, - 0.02 to 0.02, - 1.52 to 1.32, and - 68.02 to 63.21, respectively. Manual segmentation lasted typically 30 minutes vs about one minute with the CNN-based approach. The maximal deviation at manual re-segmentation was for the four parameters 0% to 0.5% with the same and 0% to 1% with different operators.
Conclusion
The CNN-based method was faster and provided values for Vol, SUVmean, SUVmax, and SUVtotal comparable to the manually obtained ones. This AI-based segmentation approach appears to offer a more reproducible and much faster substitute for slow and cumbersome manual segmentation of the heart.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 11 Aug 2021; epub ahead of print
Piri R, Edenbrandt L, Larsson M, Enqvist O, ... Gerke O, Høilund-Carlsen PF
J Nucl Cardiol: 11 Aug 2021; epub ahead of print | PMID: 34386861
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Impact:
Abstract

Quantitative myocardial perfusion response to adenosine and regadenoson in patients with suspected coronary artery disease.

Kero T, Saraste A, Lagerqvist B, Sörensen J, ... Lubberink M, Knuuti J
Background
The aim of the present study was to compare the quantitative flow responses of regadenoson against adenosine using cardiac 15O-water PET imaging in patients with suspected or known coronary artery disease (CAD).
Methods
Hyperemic myocardial blood flow (MBF) after adenosine and regadenoson was compared using correlation and Bland-Altman analysis in 21 patients who underwent rest and adenosine 15O-water PET scans followed by rest and regadenoson 15O-water PET scans.
Results
Global mean (± SD) MBF values at rest and stress were 0.92 ± 0.27 and 2.68 ± 0.80 mL·g·min for the adenosine study and 0.95 ± 0.29 and 2.76 ± 0.79 mL·g·min for the regadenoson study (P = 0.55 and P = 0.49). The correlations between global and regional adenosine- and regadenoson-based stress MBF were strong (r = 0.80 and r = 0.77). The biases were small for both global and regional MBF comparisons (0.08 and 0.09 mL·min·g), but the limits of agreement were wide for stress MBF.
Conclusion
The correlation between regadenoson- and adenosine-induced hyperemic MBF was strong but the agreement was only moderate indicating that established cut-off values for 150-water PET should be used cautiously if using regadenoson as vasodilator.

© 2021. The Author(s).

J Nucl Cardiol: 11 Aug 2021; epub ahead of print
Kero T, Saraste A, Lagerqvist B, Sörensen J, ... Lubberink M, Knuuti J
J Nucl Cardiol: 11 Aug 2021; epub ahead of print | PMID: 34386859
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Impact:
Abstract

Dobutamine stress PET/CT for assessment of hemodynamic significance of coronary myocardial bridges.

Abadie B, Jaber W
Myocardial bridges are common and often benign, but can cause hemodynamically significant obstruction of blood flow with stress. Dobutamine stress positron emission tomography/computed tomography (PET/CT) is a powerful tool for non-invasively assessing for ischemia. We present a case of using dobutamine stress PET/CT to determine the significance of a myocardial bridge.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 04 Aug 2021; epub ahead of print
Abadie B, Jaber W
J Nucl Cardiol: 04 Aug 2021; epub ahead of print | PMID: 34355308
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Impact:
Abstract

Diagnostic accuracy of dynamic CZT-SPECT in coronary artery disease. A systematic review and meta-analysis.

Panjer M, Dobrolinska M, Wagenaar NRL, Slart RHJA
Background
With the appearance of cadmium-zinc-telluride (CZT) cameras, dynamic myocardial perfusion imaging (MPI) has been introduced, but comparable data to other MPI modalities, such as quantitative coronary angiography (CAG) with fractional flow reserve (FFR) and positron emission tomography (PET), are lacking. This study aimed to evaluate the diagnostic accuracy of dynamic CZT single-photon emission tomography (SPECT) in coronary artery disease compared to quantitative CAG, FFR, and PET as reference.
Materials and methods
Different databases were screened for eligible citations performing dynamic CZT-SPECT against CAG, FFR, or PET. PubMed, OvidSP (Medline), Web of Science, the Cochrane Library, and EMBASE were searched on the 5th of July 2020. Studies had to meet the following pre-established inclusion criteria: randomized controlled trials, retrospective trails or observational studies relevant for the diagnosis of coronary artery disease, and performing CZT-SPECT and within half a year the methodological references. Studies which considered coronary stenosis between 50% and 70% as significant based only on CAG were excluded. Data extracted were sensitivity, specificity, likelihood ratios, and diagnostic odds ratios. Quality was assessed with QUADAS-2 and statistical analysis was performed using a bivariate model.
Results
Based on our criteria, a total of 9 studies containing 421 patients were included. For the assessment of CZT-SPECT, the diagnostic value pooled analysis with a bivariate model was calculated and yielded a sensitivity of 0.79 (% CI 0.73 to 0.85) and a specificity of 0.85 (95% CI 0.74 to 0.92). Diagnostic odds ratio (DOR) was 17.82 (95% CI 8.80 to 36.08, P < 0.001). Positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 3.86 (95% CI 2.76 to 5.38, P < 0.001) and 0.21 (95% CI 0.13 to 0.33, P < 0.001), respectively.
Conclusion
Based on the results of the current systematic review and meta-analysis, dynamic CZT-SPECT MPI demonstrated a good sensitivity and specificity to diagnose CAD as compared to the gold standards. However, due to the heterogeneity of the methodologies between the CZT-SPECT MPI studies and the relatively small number of included studies, it warrants further well-defined study protocols.

© 2021. The Author(s).

J Nucl Cardiol: 03 Aug 2021; epub ahead of print
Panjer M, Dobrolinska M, Wagenaar NRL, Slart RHJA
J Nucl Cardiol: 03 Aug 2021; epub ahead of print | PMID: 34350553
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Impact:
Abstract

Prognostic value of heart rate reserve in patients with suspected coronary artery disease undergoing stress myocardial perfusion imaging.

Nappi C, Petretta M, Assante R, Zampella E, ... Acampa W, Cuocolo A
Background
Chronotropic incompetence is common in patients with cardiovascular disease and is associated with increased risk of adverse events. We assessed the incremental prognostic value of heart rate reserve (HRR) over stress myocardial perfusion single-photon emission computed tomography (MPS) findings in patients with suspected coronary artery disease (CAD).
Methods
We studied 866 patients with suspected CAD undergoing exercise stress-MPS as part of their diagnostic program. The primary study endpoint was all-cause mortality. All patients were followed for at least 5 years. HRR was calculated as the difference between peak exercise and resting HR, divided by the difference of age-predicted maximal and resting HR and expressed as percentage.
Results
During 7 years follow-up, 61 deaths occurred, with a 7% cumulative event rate. Patients experiencing death were older (P < .001), and had a higher prevalence of male gender (P < .001) and diabetes (P < .05). Patients with event also had lower values of HRR (65% ± 27% vs 73% ± 18%, P < .0001) and higher prevalence of stress-induced myocardial ischemia (25% vs 8%, P < .0001). Male gender, HRR and stress-induced ischemia were independent predictors of all-cause mortality (all P < .01). HRR improved the prognostic power of a model including clinical data and MPS findings, increasing the global χ2 from 66 to 82 (P < .005).
Conclusions
Chronotropic incompetence has independent and incremental prognostic value in predicting all-cause mortality in patients with suspected CAD undergoing exercise stress-MPS. Hence, the evaluation of HRR may further improve patients\' risk stratification.

© 2021. The Author(s).

J Nucl Cardiol: 02 Aug 2021; epub ahead of print
Nappi C, Petretta M, Assante R, Zampella E, ... Acampa W, Cuocolo A
J Nucl Cardiol: 02 Aug 2021; epub ahead of print | PMID: 34346030
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Impact:
Abstract

From the clinical spectrum of myocardial calcification to a cardiovascular imaging perspective.

Mansour L, Ancedy C, Bellouche Y, Mansour MJ, Le Ven F
We herein report the case of a 74-year-old man with recurrent transient ischemic attacks and falls who was found to have an unusual large mass of the interventricular septum. After extensive workup, isolated myocardial calcification was confirmed using multimodality cardiovascular imaging. This rare finding might be a reflecting cause of the patient\'s clinical presentation.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 02 Aug 2021; epub ahead of print
Mansour L, Ancedy C, Bellouche Y, Mansour MJ, Le Ven F
J Nucl Cardiol: 02 Aug 2021; epub ahead of print | PMID: 34346029
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Impact:
Abstract

Does quantification of [C]meta-hydroxyephedrine and [N]ammonia kinetics improve risk stratification in ischemic cardiomyopathy.

Wang JZ, Zelt JGE, Kaps N, Lavallee A, ... Canty JM, deKemp RA
Background
In ischemic cardiomyopathy patients, cardiac sympathetic nervous system dysfunction is a predictor of sudden cardiac arrest (SCA). This study compared abnormal innervation and perfusion measured by [11C]meta-hydroxyephedrine (HED) vs [13N]ammonia (NH3), conventional uptake vs parametric tracer analysis, and their SCA risk discrimination.
Methods
This is a sub-study analysis of the prospective PAREPET trial, which followed ischemic cardiomyopathy patients with reduced left ventricular ejection fraction (LVEF ≤ 35%) for events of SCA. Using n = 174 paired dynamic HED and NH3 positron emission tomography (PET) scans, regional defect scores (%LV extent × severity) were calculated using HED and NH3 uptake, as well as HED distribution volume and NH3 myocardial blood flow by kinetic modeling.
Results
During 4.1 years follow-up, there were 27 SCA events. HED defects were larger than NH3, especially in the lowest tertile of perfusion abnormality (P < .001). Parametric defects were larger than their respective tracer uptake defects (P < .001). SCA risk discrimination was not significantly improved with parametric or uptake mismatch (AUC = 0.73 or 0.70) compared to HED uptake defect scores (AUC = 0.67).
Conclusion
Quantification of HED distribution volume and NH3 myocardial blood flow produced larger defects than their respective measures of tracer uptake, but did not lead to improved SCA risk stratification vs HED uptake alone.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 01 Aug 2021; epub ahead of print
Wang JZ, Zelt JGE, Kaps N, Lavallee A, ... Canty JM, deKemp RA
J Nucl Cardiol: 01 Aug 2021; epub ahead of print | PMID: 34341953
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Impact:
Abstract

Quantitative myocardial perfusion SPECT/CT for the assessment of myocardial tracer uptake in patients with three-vessel coronary artery disease: Initial experiences and results.

Lehner S, Nowak I, Zacherl M, Brosch-Lenz J, ... Bartenstein P, Todica A
Background
To evaluate quantitative myocardial perfusion SPECT/CT datasets for routine clinical reporting and the assessment of myocardial tracer uptake in patients with severe TVCAD.
Methods
MPS scans were reconstructed as quantitative SPECT datasets using CTs from internal (SPECT/CT, Q_INT) and external (PET/CT, Q_EXT) sources for attenuation correction. TPD was calculated and compared to the TPD from non-quantitative SPECT datasets of the same patients. SUVmax, SUVpeak, and SUVmean were compared between Q_INT and Q_EXT SPECT datasets. Global SUVmax and SUVpeak were compared between patients with and without TVCAD.
Results
Quantitative reconstruction was feasible. TPD showed an excellent correlation between quantitative and non-quantitative SPECT datasets. SUVmax, SUVpeak, and SUVmean showed an excellent correlation between Q_INT and Q_EXT SPECT datasets, though mean SUVmean differed significantly between the two groups. Global SUVmax and SUVpeak were significantly reduced in patients with TVCAD.
Conclusions
Absolute quantification of myocardial tracer uptake is feasible. The method seems to be robust and principally suitable for routine clinical reporting. Quantitative SPECT might become a valuable tool for the assessment of severe coronary artery disease in a setting of balanced ischemia, where potentially life-threatening conditions might otherwise go undetected.

© 2021. The Author(s).

J Nucl Cardiol: 01 Aug 2021; epub ahead of print
Lehner S, Nowak I, Zacherl M, Brosch-Lenz J, ... Bartenstein P, Todica A
J Nucl Cardiol: 01 Aug 2021; epub ahead of print | PMID: 34341952
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Impact:
Abstract

Relation between myocardial blood flow and cardiac events in diabetic patients with suspected coronary artery disease and normal myocardial perfusion imaging.

Assante R, Mainolfi CG, Zampella E, Gaudieri V, ... Cuocolo A, Acampa W
Background
We assessed the prognostic value of structural abnormalities and coronary vasodilator function in diabetic patients referred to a PET/CT for suspected coronary artery disease (CAD).
Methods
We studied 451 diabetics and 451 nondiabetics without overt CAD and normal myocardial perfusion. Myocardial blood flow (MBF) was computed from the dynamic rest and stress imaging. Myocardial flow reserve (MFR) was defined as ratio of hyperemic to baseline MBF and was considered reduced when < 2.
Results
During a mean follow-up of 44 months 33 events occurred. Annualized event rate (AER) was higher in diabetic than nondiabetic patients (1.4% vs 0.3%, P < .001). Diabetic patients with reduced MFR had higher AER compared to those with preserved MFR (3.3% vs 0.4%, P  < .001). At Cox analysis, age, BMI and reduced MFR were independent predictors of events in diabetic patients. Patients with diabetes and reduced MFR had lower event-free survival compared to nondiabetic patients and MFR < 2 (P < .001). Event-free survival was similar in patients with diabetes and normal MFR and those without diabetes and reduced MFR.
Conclusions
Diabetic patients with reduced MFR had higher AER and lower event-free survival compared to those with preserved MFR and to nondiabetic patients.

© 2021. The Author(s).

J Nucl Cardiol: 30 Jul 2021; 28:1222-1233
Assante R, Mainolfi CG, Zampella E, Gaudieri V, ... Cuocolo A, Acampa W
J Nucl Cardiol: 30 Jul 2021; 28:1222-1233 | PMID: 33599942
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Impact:
Abstract

Feasibility and application of trimetazidine in F-FDG PET myocardial metabolic imaging of diabetic mellitus patients with severe coronary artery disease: A prospective, self-controlled study.

Shao X, Chen Y, Chen Y, Zhang F, ... Niu R, Wang Y
Background
18F-FDG PET myocardial metabolic imaging (MMI) is sometimes uninterpretable due to background activity from uncontrolled glucose homeostasis in diabetic mellitus (DM) patients. Trimetazidine is an oral medication that promotes the transformation of myocardial energy supply from free fatty acids to glucose. We aimed to investigate the feasibility and application of trimetazidine in 18F-FDG PET MMI of DM patients.
Methods
With DM patients exhibiting severe coronary artery disease (CAD) symptoms serving as self-controls, the effects of trimetazidine on PET MMI image quality, myocardial viability assessment, quantitative analytical parameters, and 18F-FDG uptake of different myocardial segments were elucidated.
Results
The image quality of 18F-FDG MMI was graded visually as good, moderate, and uninterpretable. After trimetazidine, grades of good, moderate, and uninterpretable were observed in 14 (60.9%), 8 (34.8%), and 1 (4.3%) patients, respectively, and in 4 (17.4%), 15 (65.2%), 4 (17.4%) patients without trimetazidine. The myocardial SUV and myocardial to blood pool SUV ratio (M/B ratio) were significantly higher after trimetazidine administration than those before (3.11 ± 1.07 vs 2.32 ± 1.00, 2.67 ± 1.41 vs 1.81 ± 0.75, P all < 0.01). 6 (3, 7) viable myocardium segments were detected with a mismatch score of 10 (6, 17) after trimetazidine, significantly higher than those before trimetazidine [5 (2, 7) and 8 (2, 17), P < 0.05]. Meanwhile, the 18F-FDG uptake in myocardial segments with decreased and normal perfusion showed different ranges of increase (by 15.30%-57.77%).
Conclusion
Trimetazidine is feasible and effective in DM patients with severe CAD before 18F-FDG PET MMI, which can significantly improve the image quality and increase the number of viable myocardium segments detected.
Trial registry
The study was registered in the Chinese Clinical Trial Registry (ChiCTR2000038559).

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 29 Jul 2021; epub ahead of print
Shao X, Chen Y, Chen Y, Zhang F, ... Niu R, Wang Y
J Nucl Cardiol: 29 Jul 2021; epub ahead of print | PMID: 34331217
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Impact:
Abstract

An optimized imaging protocol for [Tc]Tc-DPD scintigraphy and SPECT/CT quantification in cardiac transthyretin (ATTR) amyloidosis.

Schatka I, Bingel A, Schau F, Bluemel S, ... Rogasch JMM, Wetz C
Background
In [99mTc]Tc-DPD scintigraphy for myocardial ATTR amyloidosis, planar images 3 hour p.i. and SPECT/CT acquisition in L-mode are recommended. This study investigated if earlier planar images (1 hour p.i.) are beneficial and if SPECT/CT acquisition should be preferred in H-mode (180° detector angle) or L-mode (90°).
Methods
In SPECT/CT phantom measurements (NaI cameras, N = 2; CZT, N = 1), peak contrast recovery (CRpeak) was derived from sphere inserts or myocardial insert (cardiac phantom; signal-to-background ratio [SBR], 10:1 or 5:1). In 25 positive and 38 negative patients (reference: endomyocardial biopsy or clinical diagnosis), Perugini scores and heart-to-contralateral (H/CL) count ratios were derived from planar images 1 hour and 3 hour p.i.
Results
In phantom measurements, accuracy of myocardial CRpeak at SBR 10:1 (H-mode, 0.95-0.99) and reproducibility at 5:1 (H-mode, 1.02-1.14) was comparable for H-mode and L-mode. However, L-mode showed higher variability of background counts and sphere CRpeak throughout the field of view than H-mode. In patients, sensitivity/specificity were ≥ 95% for H/CL ratios at both time points and visual scoring 3 hour. At 1 hour, visual scores showed specificity of 89% and reduced reader\'s confidence.
Conclusions
Early DPD images provided no additional value for visual scoring or H/CL ratios. In SPECT/CT, H-mode is preferred over L-mode, especially if quantification is applied apart from the myocardium.

© 2021. The Author(s).

J Nucl Cardiol: 29 Jul 2021; epub ahead of print
Schatka I, Bingel A, Schau F, Bluemel S, ... Rogasch JMM, Wetz C
J Nucl Cardiol: 29 Jul 2021; epub ahead of print | PMID: 34331215
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Impact:
Abstract

Diagnostic challenges in primary cardiac lymphoma, the opportunity of F-FDG PET/CT integrated with contrast-enhanced CT.

Liu E, Huang J, Dong H, Chen Z, ... Wang S, Liu Z
Background
The purpose of this study was to retrospectively evaluate the value of 18F-FDG PET/CT integrated with contrast-enhanced CT (CECT) in the differential diagnosis of primary cardiac lymphomas (PCLs) and primary cardiac angiosarcomas (PCAs).
Methods
Clinical and imaging data of patients with PCLs and PCAs were collected. All patients underwent preoperative 18F-FDG PET/CT and thoracic CECT. The enhancement pattern and tumor morphology were analyzed using CECT images. The intensity- and volume-based PET parameters of cardiac lesions were analyzed. The performance characteristics of all parameters were assessed.
Results
Nine patients with PCL and eight patients with PCA were analyzed. There were significant differences in SUVmax (t = 3.790, P = .002), SUVmean (t = 4.273, P = .001), metabolic tumor volume (U = 13.00, P = .027), tumor-to-liver ratio (U = 10.00, P = .011), and total lesion glycolysis (U = 4.0, P = .001) between PCLs and PC18As. There were significant differences in the enhancement pattern of tumors (P = .002) and tumor morphology (P = .015). The combination of F-FDG PET/CT and CECT improved the diagnostic accuracy, and the combination cutoff (SUVmean > 5.17) could reach 100%, but the difference was not statistically significant (P > .05).
Conclusion
The intensity- and volume-based PET parameters of PCL were significantly higher than those of PCA. The enhancement pattern and tumor morphology were also different. According to these characteristics, the two most common types of primary cardiac malignancies can be differentiated.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 26 Jul 2021; epub ahead of print
Liu E, Huang J, Dong H, Chen Z, ... Wang S, Liu Z
J Nucl Cardiol: 26 Jul 2021; epub ahead of print | PMID: 34318397
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Impact:
Abstract

SPECT/CT imaging of inflammation and calcification in human carotid atherosclerosis to identify the plaque at risk of rupture.

Van der Heiden K, Barrett HE, Meester EJ, van Gaalen K, ... Bernsen MR, Gijsen FJH
Background
Calcification and inflammation are atherosclerotic plaque compositional biomarkers that have both been linked to stroke risk. The aim of this study was to evaluate their co-existing prevalence in human carotid plaques with respect to plaque phenotype to determine the value of hybrid imaging for the detection of these biomarkers.
Methods
Human carotid plaque segments, obtained from endarterectomy, were incubated in [111In]In-DOTA-butylamino-NorBIRT ([111In]In-Danbirt), targeting Leukocyte Function-associated Antigen-1 (LFA-1) on leukocytes. By performing SPECT/CT, both inflammation from DANBIRT uptake and calcification from CT imaging were assessed. Plaque phenotype was classified using histology.
Results
On a total plaque level, comparable levels of calcification volume existed with different degrees of inflammation and vice versa. On a segment level, an inverse relationship between calcification volume and inflammation was evident in highly calcified segments, which classify as fibrocalcific, stable plaque segments. In contrast, segments with little or no calcification presented with a moderate to high degree of inflammation, often coinciding with the more dangerous fibrous cap atheroma phenotype.
Conclusion
Calcification imaging alone can only accurately identify highly calcified, stable, fibrocalcific plaques. To identify high-risk plaques, with little or no calcification, hybrid imaging of calcification and inflammation could provide diagnostic benefit.

© 2021. The Author(s).

J Nucl Cardiol: 26 Jul 2021; epub ahead of print
Van der Heiden K, Barrett HE, Meester EJ, van Gaalen K, ... Bernsen MR, Gijsen FJH
J Nucl Cardiol: 26 Jul 2021; epub ahead of print | PMID: 34318395
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Impact:
Abstract

Hemiplegic migraine episode triggered by regadenoson.

Elsadany M, McMahon SR, Mehla S, Duvall WL
SPECT and PET myocardial perfusion imaging (MPI) are widely used to evaluate patients for coronary artery disease. Regadenoson (a selective A2A adenosine receptor agonist) is a commonly used vasodilator agent for stress MPI because of its safety profile and ease of use. Common adverse reactions such as headache, shortness of breath, flushing, and chest and abdominal discomfort are typically mild and can be effectively reversed using methylxanthines such as aminophylline and caffeine. Neurological adverse reactions such as seizure and stroke have rarely been reported with the use of regadenoson. The hemodynamic changes associated with regadenoson administration, such as an exaggerated hypotensive or hypertensive response, may be the cause for the reported cerebrovascular accidents. Activation of central nervous system A2A adenosine receptors is thought to be responsible for seizure episodes in patients with or without known histories of seizure. A2A adenosine receptors activation is also believed to play a role in headaches and migraine. This patient reported who has a history of hemiplegic migraine developed left side weakness and headache following the administration of regadenoson during a PET MPI study. Imaging work-up to rule out cerebrovascular accident was normal. After 1 hour from the onset of his symptoms, his weakness and headache significantly improved with complete resolution within 24 hours. We concluded that regadenoson triggered a hemiplegic migraine episode in this patient, which has not been previously reported in the literature. It may be prudent to avoid regadenoson and adenosine use in patients with a history of hemiplegic migraine.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 24 Jul 2021; epub ahead of print
Elsadany M, McMahon SR, Mehla S, Duvall WL
J Nucl Cardiol: 24 Jul 2021; epub ahead of print | PMID: 34308528
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Impact:
Abstract

Diagnosis of left ventricular hypertrophy using non-ECG-gated O-water PET.

Sörensen J, Nordström J, Baron T, Mörner S, ... Magnusson P, Harms HJ
Aim
To develop a method for diagnosing left ventricular (LV) hypertrophy from cardiac perfusion 15O-water positron emission tomography (PET).
Methods
We retrospectively pooled data from 139 subjects in four research cohorts. LV remodeling patterns ranged from normal to severe eccentric and concentric hypertrophy. 15O-water PET scans (n = 197) were performed with three different PET devices. A low-end scanner (66 scans) was used for method development, and remaining scans with newer devices for a blinded evaluation. Dynamic data were converted into parametric images of perfusable tissue fraction for semi-automatic delineation of the LV wall and calculation of LV mass (LVM) and septal wall thickness (WT). LVM and WT from PET were compared to cardiac magnetic resonance (CMR, n = 47) and WT to 2D-echocardiography (2DE, n = 36). PET accuracy was tested using linear regression, Bland-Altman plots, and ROC curves. Observer reproducibility were evaluated using intraclass correlation coefficients.
Results
High correlations were found in the blinded analyses (r ≥ 0.87, P < 0.0001 for all). AUC for detecting increased LVM and WT (> 12 mm and > 15 mm) was ≥ 0.95 (P < 0.0001 for all). Reproducibility was excellent (ICC ≥ 0.93, P < 0.0001).
Conclusion
15O-water PET might detect LV hypertrophy with high accuracy and precision.

© 2021. The Author(s).

J Nucl Cardiol: 19 Jul 2021; epub ahead of print
Sörensen J, Nordström J, Baron T, Mörner S, ... Magnusson P, Harms HJ
J Nucl Cardiol: 19 Jul 2021; epub ahead of print | PMID: 34286452
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Impact:
Abstract

Improving detection accuracy of perfusion defect in standard dose SPECT-myocardial perfusion imaging by deep-learning denoising.

Liu J, Yang Y, Wernick MN, Pretorius PH, Slomka PJ, King MA
Background
We previously developed a deep-learning (DL) network for image denoising in SPECT-myocardial perfusion imaging (MPI). Here we investigate whether this DL network can be utilized for improving detection of perfusion defects in standard-dose clinical acquisitions.
Methods
To quantify perfusion-defect detection accuracy, we conducted a receiver-operating characteristic (ROC) analysis on reconstructed images with and without processing by the DL network using a set of clinical SPECT-MPI data from 190 subjects. For perfusion-defect detection hybrid studies were used as ground truth, which were created from clinically normal studies with simulated realistic lesions inserted. We considered ordered-subset expectation-maximization (OSEM) reconstruction with corrections for attenuation, resolution, and scatter and with 3D Gaussian post-filtering. Total perfusion deficit (TPD) scores, computed by Quantitative Perfusion SPECT (QPS) software, were used to evaluate the reconstructed images.
Results
Compared to reconstruction with optimal Gaussian post-filtering (sigma = 1.2 voxels), further DL denoising increased the area under the ROC curve (AUC) from 0.80 to 0.88 (P-value < 10-4). For reconstruction with less Gaussian post-filtering (sigma = 0.8 voxels), thus better spatial resolution, DL denoising increased the AUC value from 0.78 to 0.86 (P-value < 10-4) and achieved better spatial resolution in reconstruction.
Conclusions
DL denoising can effectively improve the detection of abnormal defects in standard-dose SPECT-MPI images over conventional reconstruction.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 18 Jul 2021; epub ahead of print
Liu J, Yang Y, Wernick MN, Pretorius PH, Slomka PJ, King MA
J Nucl Cardiol: 18 Jul 2021; epub ahead of print | PMID: 34282538
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Impact:
Abstract

The assessment of left ventricular mechanical dyssynchrony from gated Tc-tetrofosmin SPECT and gated F-FDG PET by QGS: a comparative study.

Lehner S, Graner FP, Fischer M, Ilhan H, Bartenstein P, Todica A
Background
Due to partly conflicting studies, further research is warranted with the QGS software package, with regard to the performance of gated FDG PET phase analysis as compared to gated MPS as well as the establishment of possible cut-off values for FDG PET to define dyssynchrony.
Methods
Gated MPS and gated FDG PET datasets of 93 patients were analyzed with the QGS software. BW, Phase SD, and Entropy were calculated and compared between the methods. The performance of gated PET to identify dyssynchrony was measured against SPECT as reference standard. ROC analysis was performed to identify the best discriminator of dyssynchrony and to define cut-off values.
Results
BW and Phase SD differed significantly between the SPECT and PET. There was no significant difference in Entropy with a high linear correlation between methods. There was only moderate agreement between SPECT and PET to identify dyssynchrony. Entropy was the best single PET parameter to predict dyssynchrony with a cut-off point at 62%.
Conclusion
Gated MPS and gated FDG PET can assess LVMD. The methods cannot be used interchangeably. Establishing reference ranges and cut-off values is difficult due to the lack of an external gold standard. Further prospective research is necessary.

© 2021. The Author(s).

J Nucl Cardiol: 18 Jul 2021; epub ahead of print
Lehner S, Graner FP, Fischer M, Ilhan H, Bartenstein P, Todica A
J Nucl Cardiol: 18 Jul 2021; epub ahead of print | PMID: 34282536
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Impact:
Abstract

Effects of mineralocorticoid receptor antagonist eplerenone on cardiac sympathetic nerve activity and left ventricular remodeling after reperfusion therapy in patients with first ST-segment elevation myocardial infarction.

Toda K, Kasama S, Toyama T, Kasahara M, Kurabayashi M
Purpose
The activation of the renin-angiotensin-aldosterone system prevents the uptake of norepinephrine and promotes structural remodeling of the heart. The mineralocorticoid receptor antagonist (MRA) eplerenone prevents left ventricular (LV) remodeling in patients with acute myocardial infarction, but its influence on cardiac sympathetic nerve activity (CSNA) has not been determined.
Methods
We retrospectively evaluated the first ST-segment elevation myocardial infarction (STEMI) patients in our database who underwent 123I-metaiodobenzylguanidine (MIBG) scintigraphy 3 weeks after admission. Eighty-four STEMI patients after primary coronary angioplasty were selected, and used propensity score matching to compare patients who treated with MRA (N = 42), and those who did not (N = 42). The LV end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography, and plasma procollagen type III amino terminal peptide (PIIINP) was measured before and 3 weeks after treatment. The delayed total defect score (TDS), delayed heart/mediastinum count (H/M) ratio, and washout rate (WR) were determined using 123I-MIBG scintigraphy after 3 weeks.
Results
Following primary angioplasty, age, gender, risk factors, culprit coronary artery, peak serum creatine phosphokinase concentration, and recanalization time were similar in the two groups. However, the MRA group showed significantly lower TDS and WR values (TDS: 22.8 ± 8.1 vs 32.2 ± 11.5, P < 0.005; WR: 31.1 ± 9.0% vs 42.7 ± 9.9%, P < 0.001) and a significantly higher H/M ratio (2.23 ± 0.41 vs 2.03 ± 0.36, P < 0.05) than the non-MRA group. The degree of change in LV parameters, and PIIINP were more favorable in the MRA group than in the non-MRA group. Moreover, multiple linear regression analyses revealed that both WR and not MRA treatment were significant predictor for LV remodeling, along with PIIINP concentrations.
Conclusion
Administration of eplerenone improves CSNA and prevents LV remodeling in patients with a first STEMI.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 15 Jul 2021; epub ahead of print
Toda K, Kasama S, Toyama T, Kasahara M, Kurabayashi M
J Nucl Cardiol: 15 Jul 2021; epub ahead of print | PMID: 34272676
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Impact:
Abstract

Integration of quantitative absolute myocardial blood flow estimates from dynamic CZT-SPECT improves the detection of coronary artery disease.

Liu FS, Wang SY, Shiau YC, Wu YW
Background
Balanced ischemia with multi-vessel coronary artery disease (CAD) is difficult to diagnose with semiquantitative single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Dynamic cardiac SPECT provides quantitative estimations of stenosis severity and ischemic burden by assessing myocardial flow reserve (MFR) and myocardial blood flow (MBF). The aim of this study was to evaluate the incremental value of dynamic SPECT in multi-vessel coronary artery disease (CAD).
Methods
Patients with suspected CAD who underwent dynamic ECG-gated dipyridamole MPI and coronary angiography within 6 months were retrospectively reviewed. The performance of summed stress, rest and difference scores (SSS, SRS, SDS), post-stress and resting MBF (MBFs, MBFr) and MFR were compared at both patient level and vessel level.
Results
In 32 patients with 39 stenotic vessels, 12 had three-vessel disease (38%). Globally increased SSS and impaired MBF values were significantly associated with significant CAD at the patient level, but SDS and MFR were not. Regional increases in SSS and reductions in both MBFs and MBFr were significantly associated with stenotic vessels. The best cutoff value of global MBFs to predict CAD was 3.5 ml·g-1·min-1 (area under the curve, AUC = .84, P = .002). The best cutoff value of regional MBFs to detect significant stenosis was 3.6 ml·g-1·min-1 (AUC = .74, P < .001). However, the best possible cut-off values of MFR were not found. Sex-difference in both global and regional MBFr but MBFs was found, which might result in the non-significance in MFR.
Conclusions
This study validated a clinically available method to quantify MFR using dynamic CZT-SPECT. This method improved the detectability of multi-vessel CAD, and absolute MBFs was superior to MFR and other semiquantitative MPI parameters.



J Nucl Cardiol: 07 Jul 2021; epub ahead of print
Liu FS, Wang SY, Shiau YC, Wu YW
J Nucl Cardiol: 07 Jul 2021; epub ahead of print | PMID: 34240342
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Impact:
Abstract

Diagnostic safety of a machine learning-based automatic patient selection algorithm for stress-only myocardial perfusion SPECT.

Eisenberg E, Miller RJH, Hu LH, Rios R, ... Berman DS, Slomka PJ
Background
Stress-only myocardial perfusion imaging (MPI) markedly reduces radiation dose, scanning time, and cost. We developed an automated clinical algorithm to safely cancel unnecessary rest imaging with high sensitivity for obstructive coronary artery disease (CAD).
Methods and results
Patients without known CAD undergoing both MPI and invasive coronary angiography from REFINE SPECT were studied. A machine learning score (MLS) for prediction of obstructive CAD was generated using stress-only MPI and pre-test clinical variables. An MLS threshold with a pre-defined sensitivity of 95% was applied to the automated patient selection algorithm. Obstructive CAD was present in 1309/2079 (63%) patients. MLS had higher area under the receiver operator characteristic curve (AUC) for prediction of CAD than reader diagnosis and TPD (0.84 vs 0.70 vs 0.78, P < .01). An MLS threshold of 0.29 had superior sensitivity than reader diagnosis and TPD for obstructive CAD (95% vs 87% vs 87%, P < .01) and high-risk CAD, defined as stenosis of the left main, proximal left anterior descending, or triple-vessel CAD (sensitivity 96% vs 89% vs 90%, P < .01).
Conclusions
The MLS is highly sensitive for prediction of both obstructive and high-risk CAD from stress-only MPI and can be applied to a stress-first protocol for automatic cancellation of unnecessary rest imaging.



J Nucl Cardiol: 05 Jul 2021; epub ahead of print
Eisenberg E, Miller RJH, Hu LH, Rios R, ... Berman DS, Slomka PJ
J Nucl Cardiol: 05 Jul 2021; epub ahead of print | PMID: 34228341
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Impact:
Abstract

Localization of myocardial FDG uptake for prognostic risk stratification in corticosteroid-naïve cardiac sarcoidosis.

Bekki M, Tahara N, Tahara A, Sugiyama Y, ... Abe T, Fukumoto Y
Background
The localization of myocardial 18F-fluorodeoxyglucose (FDG) uptake affecting long-term clinical outcomes has not been elucidated in patients with corticosteroid-naïve cardiac sarcoidosis (CS).
Objectives
This study sought to investigate the localization of myocardial FDG uptake on positron emission tomography (PET) and myocardial perfusion abnormality to predict adverse events (AEs) for a long-term follow-up in patients with corticosteroid-naïve CS.
Methods
Consecutive 90 patients with clinical suspicion of CS who underwent FDG-PET imaging to assess for inflammation were enrolled. AEs were defined as a composite of sustained ventricular tachycardia (VT), heart transplantation, and all-cause death, which were ascertained by medical records, defibrillator interrogation, and telephone interviews.
Results
Of 90 patients, 42 patients (mean age 62.9 ± 12.0 years; 76.2% females) were confirmed active cardiac involvement. Over a median follow-up of 4.9 years, 15 patients with CS experienced AEs including 6 sustained ventricular tachycardias (VT) and 9 deaths. Cox proportional-hazards model after adjustment for left ventricular systolic dysfunction revealed that FDG uptake in the right ventricle (RV) or basal anterolateral area of the left ventricle (LV) with myocardial perfusion abnormality was predictive of AEs.
Conclusions
FDG uptake in the RV or basal anterolateral area of the LV with myocardial perfusion abnormality provides long-term prognostic risk stratification in patients with corticosteroid-naïve CS.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 05 Jul 2021; epub ahead of print
Bekki M, Tahara N, Tahara A, Sugiyama Y, ... Abe T, Fukumoto Y
J Nucl Cardiol: 05 Jul 2021; epub ahead of print | PMID: 34228338
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Impact:
Abstract

The prognostic role of cardiac positron emission tomography imaging in patients with sarcoidosis: A systematic review.

Ahmed AI, Abebe AT, Han Y, Alnabelsi T, ... Tleyjeh IM, Al-Mallah MH
Purpose
Sarcoidosis is a multi-systemic inflammatory disease of unknown etiology. Cardiac sarcoidosis (CS) has been reported in as much as 25% of patients with systemic involvement. 18Fluorodeoxyglucose (FDG) positron emission tomography (PET) has a high diagnostic sensitivity/specificity in the diagnosis of CS. The aim of this review is to summarize evidence on the prognostic role of FDG PET.
Methods
Studies were identified by searching MEDLINE from inception to October 2020. Medical subject headings (MeSH) terms for sarcoidosis; cardiac and FDG PET imaging were used. Studies of any design assessing the prognostic role of FDG PET in patients with either suspected or confirmed cardiac sarcoidosis imaging done at baseline were included. Abnormal PET was defined as abnormal metabolism (presence of focal or focal-on-diffuse uptake of FDG) OR abnormal metabolism and a perfusion defect. Studies reporting any outcome measure were included. Pooled risk ratio for the composite outcome of MACE was done.
Results
A total of 6 studies were selected for final inclusion (515 patients, 53.4% women, 19.8% racial minorities.) Studies were institution based, retrospective in design and enrolled consecutive patients. All were observational in nature and published in English. All studies used a qualitative assessment of PET scans (abnormal FDG uptake with or without abnormal perfusion). Two studies assessed quantitative metrics (summed stress score in segments with abnormal FDG uptake, standardized uptake value and cardiac metabolic activity.) All studies reported major adverse cardiovascular events (MACE) as a composite outcome. After a mean follow up ranging from 1.4 to 4.1 years, there were a total of 105 MACE. All studies included death (either all-cause death or sudden cardiac death) and ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation) as a component of MACE. Four of the six studies adjusted for several characteristics in their analysis. All four studies used left ventricular ejection fraction (LVEF). However, other adjustment variables were not consistent across studies. Five studies found a positive prognostic association with the primary outcome, two of which assessing right ventricular uptake.
Conclusion
Although available evidence indicates FDG PET can be used in the risk stratification of patients with CS, our findings show further studies are needed to quantify the effect in this patient group.



J Nucl Cardiol: 05 Jul 2021; epub ahead of print
Ahmed AI, Abebe AT, Han Y, Alnabelsi T, ... Tleyjeh IM, Al-Mallah MH
J Nucl Cardiol: 05 Jul 2021; epub ahead of print | PMID: 34228337
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Impact:
Abstract

Transient ischemic dilation or transient RV visualization in patients with normal SPECT stress myocardial perfusion imaging: Correlation with CT coronary artery calcium scoring and coronary angiography.

Naghshtabrizi B, Alvandi M, Shaghaghi Z, Hadei SK, ... Moradi M, Rabie MAS
Background
Ancillary findings on MPI, such as transient ischemic dilation (TID) and transient right ventricular visualization (TRV), are recognized as markers of extensive CAD and predictive of adverse outcomes. They usually occur in association with stress-induced regional MPI abnormalities. However, the clinical significance of these ancillary markers in the presence of normal stress MPI is incompletely understood.
Methods
From a cohort of 564 consecutive patients referred for clinical SPECT stress MPI, 44 patients had normal stress SPECT MPI and either TID (n = 28) or TRV (n = 16). These imaging findings were correlated with CT coronary calcium (CAC), CT coronary angiography (CTA), and invasive coronary angiography (ICA) in patients with severe CAC ≥ 1000 HU. TID and TRV were quantified as stress/rest ratios. Severe CAD was defined as > 70% luminal stenosis on CTA or ICA.
Results
The median TID ratio was 1.23, with a range of 1.13-1.48; the median TRV ratio was 1.30, with a range of 1.20-1.48. Of 44 patients with TID or TRV, only 9 patients (20.5%) had severe obstructive > 70% CAD by angiography (6 of 28 patients (21.5%) with TID and 3 of 16 patients (19%) with TRV). Severe multi-vessel CAD occurred in only 2 of 44 patients (4.5%). In contrast, of 9 patients with CAC > 1000 HU, 6 (67%) had severe obstructive CAD.
Conclusion
In patients with normal stress SPECT MPI and TID or TRV, the incidence of severe obstructive CAD was relatively low and predominantly single-vessel CAD. These findings do not support the concept that TID or TRV with normal stress MPI is predictive of high-risk CAD.



J Nucl Cardiol: 05 Jul 2021; epub ahead of print
Naghshtabrizi B, Alvandi M, Shaghaghi Z, Hadei SK, ... Moradi M, Rabie MAS
J Nucl Cardiol: 05 Jul 2021; epub ahead of print | PMID: 34228333
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Impact:
Abstract

MIBG cardiac imaging compared to ejection fraction in evaluation of cardiotoxicity: a systematic review.

Arrais TR, Cavalli GD, Dos Santos BT, Pereira GB, ... Grossman GB, Biolo A
Background
Advances in diagnosis and treatment of cancer has improved survival but resulted in increased cardiotoxic effects. The decrease in left ventricular ejection fraction (EF), one of the pillars of diagnosis of cardiotoxicity, seems to be a late process in the evolution of the disease, so 123I-metaiodobenzylguanidine (MIBG) cardiac imaging has been proposed to detect early cardiac impairment. The aim of this systematic review was to evaluate the performance of MIBG cardiac scan in this scenario.
Methods and results
A systematic search was conducted in five international databases comparing MIBG parameters with EF for evaluation of cardiotoxicity. Twelve studies were included and separated in three groups. First, studies evaluating patients with established cardiotoxicity, in which EF was reduced and MIBG parameters were abnormal. Second, studies analyzing patients during or after treatment compared to controls, with MIBG parameters significantly different between groups in most studies, even when EF remained normal. Finally, studies analyzing anthracycline (ATC) dose-related changes, with alteration in MIBG parameters occurring even when EF was preserved.
Conclusion
Although studies had high methodological variability, cardiac sympathetic innervation imaging seems to be a promising tool for assessing early cardiotoxicity. Further studies are needed to analyze its diagnostic value in this scenario.



J Nucl Cardiol: 05 Jul 2021; epub ahead of print
Arrais TR, Cavalli GD, Dos Santos BT, Pereira GB, ... Grossman GB, Biolo A
J Nucl Cardiol: 05 Jul 2021; epub ahead of print | PMID: 34228328
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Impact:
Abstract

Outcomes of patients with moderate-to-severe Ischemia excluded from the ischemia trial.

Al-Mallah MH, Ahmed AI, Nabi F, Chang SM, ... Zoghbi WA, Mahmarian JJ
Background
The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial showed no difference in outcomes between medical therapy vs coronary revascularization in the management of patients with stable coronary artery disease. We aimed to determine the percentage of patients with at least moderate ischemia that would have been eligible for enrollment and evaluate the outcomes of those who would not.
Methods
Consecutive patients who underwent cardiac single-photon emission computed tomography (SPECT) between April 2016 and September 2019 were identified and all-cause mortality was determined.
Results
There were a total of 1508 patients (mean age 67 ± 11.6 years, 69.5% males) with any perfusion defect on SPECT. Patients had a high prevalence of cardiac risk factors (73.4% with hypertension and 54.4% with diabetes mellitus.) Nearly half (709, 47%) had moderate-to-severe ischemia but over two-thirds (479/709, 66.3%) had at least one ISCHEMIA trial exclusion criteria. Patients meeting ISCHEMIA enrollment criteria had a significantly lower all-cause mortality than those who would have been excluded (3.91% vs. 11.3%, respectively, P < .001).
Conclusion
Our results show that ISCHEMIA selected a relatively small subset of lower risk patients among the larger higher risk group of patients with moderate-to-severe ischemia typical to most cardiology centers.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 05 Jul 2021; epub ahead of print
Al-Mallah MH, Ahmed AI, Nabi F, Chang SM, ... Zoghbi WA, Mahmarian JJ
J Nucl Cardiol: 05 Jul 2021; epub ahead of print | PMID: 34324083
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Impact:
Abstract

Reasons for discordance between positron emission tomography (PET) myocardial perfusion imaging (MPI) results and subsequent management.

Thomas M, Spertus JA, Kennedy KF, Thompson RC, ... Bateman TM, Patel KK
Background
Referral patterns to coronary angiography following positron emission tomography (PET) myocardial perfusion imaging (MPI) and reasons for non-referral following abnormal PET MPI are largely unknown.
Methods
Referral rates to coronary angiography within 90 days post PET MPI were determined. A random subset of 100 patients with severe (≥ 10%) ischemia on MPI between 2014-16 who were not referred for angiography were examined to better understand reasons as to why patients with high-risk MPI findings did not undergo coronary angiography.
Results
Among 19,282 unique patients, overall rate of 90-day coronary angiography was 18.5% (3574/19282). Among patients with severe ischemia, 64.1% (1930/3011) underwent angiography within 90 days; the rate was lower in those with mild-moderate (20.6% [1010/4898]) and no ischemia (5.6% [634/11373]). In the random sample of 100 patients, the most common physician reasons for non-referral were uncertainty regarding whether the test results were responsible for the patient\'s presenting symptoms, renal failure, and patient age, frailty, or cognitive status, while patient preference for medical management was by far the most common patient reason.
Conclusion
Referral rates for coronary angiography after PET correlate with severity of ischemia. However, there appear to be opportunities to reconsider testing for instances when results will not change clinical management.



J Nucl Cardiol: 23 Jun 2021; epub ahead of print
Thomas M, Spertus JA, Kennedy KF, Thompson RC, ... Bateman TM, Patel KK
J Nucl Cardiol: 23 Jun 2021; epub ahead of print | PMID: 34169476
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Impact:
Abstract

F-FDG PET/CT improves diagnostic certainty in native and prosthetic valve Infective Endocarditis over the modified Duke Criteria.

Primus CP, Clay TA, McCue MS, Wong K, ... Woldman S, Menezes LJ
Background
International guidance recognizes the shortcomings of the modified Duke Criteria (mDC) in diagnosing infective endocarditis (IE) when transoesophageal echocardiography (TOE) is equivocal. 18F-FDG PET/CT (PET) has proven benefit in prosthetic valve endocarditis (PVE), but is restricted to extracardiac manifestations in native disease (NVE). We investigated the incremental benefit of PET over the mDC in NVE.
Methods
Dual-center retrospective study (2010-2018) of patients undergoing myocardial suppression PET for NVE and PVE. Cases were classified by mDC pre- and post-PET, and evaluated against discharge diagnosis. Receiver Operating Characteristic (ROC) analysis and net reclassification index (NRI) assessed diagnostic performance. Valve standardized uptake value (SUV) was recorded.
Results
69/88 PET studies were evaluated across 668 patients. At discharge, 20/32 had confirmed NVE, 22/37 PVE, and 19/69 patients required surgery. PET accurately re-classified patients from possible, to definite or rejected (NRI: NVE 0.89; PVE 0.90), with significant incremental benefit in both NVE (AUC 0.883 vs 0.750) and PVE (0.877 vs 0.633). Sensitivity and specificity were 75% and 92% in NVE; 87% and 86% in PVE. Duration of antibiotics and C-reactive Protein level did not impact performance. No diagnostic SUV cut-off was identified.
Conclusion
PET improves diagnostic certainty when combined with mDC in NVE and PVE.



J Nucl Cardiol: 23 Jun 2021; epub ahead of print
Primus CP, Clay TA, McCue MS, Wong K, ... Woldman S, Menezes LJ
J Nucl Cardiol: 23 Jun 2021; epub ahead of print | PMID: 34169473
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Impact:
Abstract

N-ammonia positron emission tomography-derived endocardial strain for the assessment of ischemia using feature-tracking in high-resolution cine imaging.

Kawakubo M, Nagao M, Yamamoto A, Nakao R, ... Sasaki M, Sakai S
Background
Assessing endocardial strain using a single 13N-ammonia positron emission tomography (PET) scan would be clinically useful, given the association between ischemia and myocardial deformation. However, no software has been developed for strain analysis using PET. We evaluated the clinical potential of feature tracking-derived strain values measured using PET, based on associations with the myocardial flow reserve (MFR).
Methods and results
This retrospective study included 95 coronary artery disease patients who underwent myocardial 13N-ammonia PET. Semi-automatic measurements were made using a feature-tracking technique during myocardial cine imaging, and values were calculated using a 16-segment model. Adenosine-stressed global circumferential strain (CS) and global longitudinal strain (LS) values were compared with global MFR values. Stressed and resting global strain values were also compared. Global strain values were significantly lower in 39 patients with abnormal MFRs [< 2.0] than in 56 patients with normal MFRs [≥ 2.0]. The global CS values in the stressed state were significantly decreased than the resting state values in patients with abnormal MFRs.
Conclusions
This study applied endocardial feature-tracking to 13N-ammonia PET, and the results suggested that blood flow and myocardial motility could be clinically assessed in ischemic patients using a single PET scan.



J Nucl Cardiol: 10 Jun 2021; epub ahead of print
Kawakubo M, Nagao M, Yamamoto A, Nakao R, ... Sasaki M, Sakai S
J Nucl Cardiol: 10 Jun 2021; epub ahead of print | PMID: 34117615
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Impact:
Abstract

Utility of nuclear cardiovascular imaging in the cardiac intensive care unit.

Schenone AL, Hutt E, Cremer P, Jaber WA
The contemporary Cardiac Intensive Care Unit (CICU) has evolved into a complex unit that admits a heterogeneous mix of patients with a wide range of acute cardiovascular diseases often complicated by multi-organ failure. Although electrocardiography (ECG) and echocardiography are well-established as first-line diagnostic modalities for assessing patients in the CICU, nuclear cardiology imaging has emerged as a useful adjunctive diagnostic modality. The versatility, safety and accuracy of nuclear imaging (e.g., perfusion, metabolism, inflammation) for the assessment of patient with coronary artery disease, ventricular arrhythmias, infiltrative cardiomyopathies, infective endocarditis and inflammatory aortopathies has been proven useful and now often incorporated into the best practices for the management of critically ill cardiac patients. Thus, clinicians must familiarize themselves with the value and current and future applications of nuclear imaging in the management of the cardiac patient in the CICU.



J Nucl Cardiol: 08 Jun 2021; epub ahead of print
Schenone AL, Hutt E, Cremer P, Jaber WA
J Nucl Cardiol: 08 Jun 2021; epub ahead of print | PMID: 34109502
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Impact:
Abstract

Review of cardiovascular imaging in the Journal of Nuclear Cardiology 2020: positron emission tomography, computed tomography, and magnetic resonance.

AlJaroudi WA, Hage FG
Although the year 2020 was different from other years in many respects, the Journal of Nuclear Cardiology published excellent articles pertaining to imaging in patients with cardiovascular disease due to the dedication of the investigators in our field all over the world. In this review, we will summarize a selection of these articles to provide a concise review of the main advancements that have recently occurred in the field and provide the reader with an opportunity to review a wide selection of articles. We will focus on publications dealing with positron emission tomography, computed tomography, and magnetic resonance and hope that you will find this review helpful.



J Nucl Cardiol: 07 Jun 2021; epub ahead of print
AlJaroudi WA, Hage FG
J Nucl Cardiol: 07 Jun 2021; epub ahead of print | PMID: 34105040
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Impact:
Abstract

Myocardial perfusion recovery induced by an α-calcitonin gene-related peptide analogue.

Bentsen S, Sams A, Hasbak P, Edvinsson L, Kjaer A, Ripa RS
Background
Endogenous calcitonin gene-related peptide (CGRP) induces cardioprotective effects through coronary vasodilation. However, the systemic administration of CGRP induces peripheral vasodilation and positive chronotropic and inotropic effects. This study aims to examine the net effect on coronary perfusion of the systemically administered α-calcitonin gene-related peptide analogue, SAX, in rats during myocardial infarction.
Methods
Forty Sprague-Dawley rats underwent myocardial infarction. Following left anterior descending artery occlusion, [99mTc]Tc-sestamibi was administered to determine the myocardial perfusion before treatment. Twenty minutes, 24 and 48 h after [99mTc]Tc-sestamibi injection, the rats were treated with either SAX or placebo. Final infarct size was determined three weeks later by [99mTc]Tc-sestamibi SPECT/CT scan.
Results
Thirty-one rats survived the surgery and 20 completed the follow-up SPECT/CT scan (SAX n = 12; Placebo n = 8). At baseline, there was no difference in size of perfusion defect between the groups (P = .88), but at follow-up the SAX group had improved myocardial recovery compared to the placebo group (P = .04), corresponding to a relative perfusion recovery of 55% in SAX-treated rats.
Conclusion
The CGRP analogue, SAX, has a cardioprotective effect in this rat model of myocardial infarction, improving myocardial perfusion recovery after chronic occlusion of the coronary artery.



J Nucl Cardiol: 03 Jun 2021; epub ahead of print
Bentsen S, Sams A, Hasbak P, Edvinsson L, Kjaer A, Ripa RS
J Nucl Cardiol: 03 Jun 2021; epub ahead of print | PMID: 34089154
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Impact:
Abstract

CT-free attenuation correction for dedicated cardiac SPECT using a 3D dual squeeze-and-excitation residual dense network.

Chen X, Zhou B, Shi L, Liu H, ... Sinusas AJ, Liu C
Background
Attenuation correction (AC) using CT transmission scanning enables the accurate quantitative analysis of dedicated cardiac SPECT. However, AC is challenging for SPECT-only scanners. We developed a deep learning-based approach to generate synthetic AC images from SPECT images without AC.
Methods
CT-free AC was implemented using our customized Dual Squeeze-and-Excitation Residual Dense Network (DuRDN). 172 anonymized clinical hybrid SPECT/CT stress/rest myocardial perfusion studies were used in training, validation, and testing. Additional body mass index (BMI), gender, and scatter-window information were encoded as channel-wise input to further improve the network performance.
Results
Quantitative and qualitative analysis based on image voxels and 17-segment polar map showed the potential of our approach to generate consistent SPECT AC images. Our customized DuRDN showed superior performance to conventional network design such as U-Net. The averaged voxel-wise normalized mean square error (NMSE) between the predicted AC images by DuRDN and the ground-truth AC images was 2.01 ± 1.01%, as compared to 2.23 ± 1.20% by U-Net.
Conclusions
Our customized DuRDN facilitates dedicated cardiac SPECT AC without CT scanning. DuRDN can efficiently incorporate additional patient information and may achieve better performance compared to conventional U-Net.



J Nucl Cardiol: 02 Jun 2021; epub ahead of print
Chen X, Zhou B, Shi L, Liu H, ... Sinusas AJ, Liu C
J Nucl Cardiol: 02 Jun 2021; epub ahead of print | PMID: 34085168
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Impact:
Abstract

Diagnostic performance of White Blood Cell SPECT imaging against intra-operative findings in patients with a suspicion of prosthetic valve endocarditis.

Kooshki N, Grambow-Velilla J, Mahida B, Benali K, ... Rouzet F, Hyafil F
Aim
The objective of this study was to evaluate the diagnostic performance of white blood cells (WBC)-SPECT imaging in patients with suspicion of prosthetic valve endocarditis (PVE) against intra-operative findings.
Methods
36 consecutive patients who underwent cardiac surgery 30 days after WBC-SPECT imaging were identified retrospectively. Clinical, imaging, and biological results were collected from reports. WBC-SPECT results were classified as positive or negative and, if positive, the intensity of signal graded as intense or mild. Lesions observed during cardiac surgery were collected from surgeons\' reports.
Results
The 20 patients with positive WBC-SPECT study had confirmed PVE intra-operatively. Patients with intense signal on WBC-SPECT had high prevalence of abscesses (83%) compared to patients with only mild signal (12%). The three patients with negative WBC-SPECT but confirmed PVE had longer duration of antibiotic treatment before imaging and had no perivalvular abscess. Sensitivity, specificity, positive predictive and negative values, and accuracy of WBC-SPECT were measured at 87%, 100%, 100%, 81%, and 92%, respectively. Addition of WBC-SPECT results to the modified Duke score helped re-classify correctly 25% of patients from possible to definite PVE.
Conclusion
In patients with suspicion of PVE, WBC-SPECT imaging provides excellent diagnostic performance against intra-operative findings.



J Nucl Cardiol: 02 Jun 2021; epub ahead of print
Kooshki N, Grambow-Velilla J, Mahida B, Benali K, ... Rouzet F, Hyafil F
J Nucl Cardiol: 02 Jun 2021; epub ahead of print | PMID: 34085167
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Impact:
Abstract

Cardiac fibroblast activation detected by Ga-68 FAPI PET imaging as a potential novel biomarker of cardiac injury/remodeling.

Siebermair J, Köhler MI, Kupusovic J, Nekolla SG, ... Rassaf T, Rischpler C
Background
Fibroblast activation protein (FAP) as a specific marker of activated fibroblasts can be visualized by positron emission tomography (PET) using Ga-68-FAP inhibitors (FAPI). Gallium-68-labeled FAPI is increasingly used in the staging of various cancers. In addition, the first cases of theranostic approaches have been reported. In this work, we describe the phenomenon of myocardial FAPI uptake in patients who received a Ga-68 FAPI PET for tumor staging.
Method and results
Ga-68 FAPI PET examinations for cancer staging were retrospectively analyzed with respect to cardiac tracer uptake. Standardized uptake values (SUV) were correlated to clinical covariates in a univariate regression model. From 09/2018 to 11/2019 N = 32 patients underwent FAPI PET at our institution. Six out of 32 patients (18.8%) demonstrated increased localized myocardial tracer accumulation, with remote FAPI uptake being significantly higher in patients with vs without localized focal myocardial uptake (SUVmax 2.2 ± .6 vs 1.5 ± .4, P < .05 and SUVmean 1.6 ± .4 vs 1.2 ± .3, P < .05, respectively). Univariate regression demonstrated a significant correlation of coronary artery disease (CAD), age and left ventricular ejection fraction (LVEF) with remote SUVmean uptake, the latter with a very strong correlation with remote uptake (R2 = .74, P < .01).
Conclusion
Our study indicates an association of CAD, age, and LVEF with FAPI uptake. Further studies are warranted to assess if fibroblast activation can be reliably measured and may be used for risk stratification regarding early detection or progression of CAD and left ventricular remodeling.



J Nucl Cardiol: 30 May 2021; 28:812-821
Siebermair J, Köhler MI, Kupusovic J, Nekolla SG, ... Rassaf T, Rischpler C
J Nucl Cardiol: 30 May 2021; 28:812-821 | PMID: 32975729
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Impact:
Abstract

Diagnostic accuracy of SPECT and PET myocardial perfusion imaging in patients with left bundle branch block or ventricular-paced rhythm.

Vidula MK, Wiener P, Selvaraj S, Khan MS, ... Julien H, Bravo PE
Background
The difference in diagnostic accuracy of coronary artery disease (CAD) between vasodilator SPECT and PET myocardial perfusion imaging (MPI) in patients with left bundle branch block (LBBB) or ventricular-paced rhythm (VPR) is unknown.
Methods
We identified patients with LBBB or VPR who underwent either vasodilator SPECT or PET MPI and subsequent coronary angiography. LBBB/VPR-related septal and anteroseptal defects were defined as perfusion defects involving those regions in the absence of obstructive CAD in the left anterior descending artery or left main coronary artery.
Results
Of the 55 patients who underwent coronary angiography, 38 (69%) underwent SPECT and 17 patients (31%) underwent PET. PET compared to SPECT demonstrated higher sensitivity (88% vs 60%), specificity (56% vs 14%), positive predictive value (64% vs 20%), negative predictive value (83% vs 50%), and overall superior diagnostic accuracy (AUC .72 (95% CI .50-.93) vs .37 (95% CI .20-.54), P = .01) to detect obstructive CAD. LBBB/VPR-related septal and anteroseptal defects were more common with SPECT compared to PET (septal: 72% vs 17%, P = .001; anteroseptal: 47% vs 8%, P = .02).
Conclusions
PET has higher diagnostic accuracy when compared to SPECT for the detection of obstructive CAD in patients with LBBB or VPR.



J Nucl Cardiol: 30 May 2021; 28:981-988
Vidula MK, Wiener P, Selvaraj S, Khan MS, ... Julien H, Bravo PE
J Nucl Cardiol: 30 May 2021; 28:981-988 | PMID: 33083984
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Impact:
Abstract

Multimodality molecular imaging: Gaining insights into the mechanisms linking chronic stress to cardiovascular disease.

Osborne MT, Abohashem S, Zureigat H, Abbasi TA, Tawakol A
Positron emission tomography (PET) imaging can yield unique mechanistic insights into the pathophysiology of atherosclerosis. 18F-fluorodeoxyglucose (18F-FDG), a radiolabeled glucose analog, is retained by cells in proportion to their glycolytic activity. While 18F-FDG accumulates within several cell types in the arterial wall, its retention correlates with macrophage content, providing an index of arterial inflammation (ArtI) which predicts subsequent cardiovascular disease (CVD) events. Furthermore, 18F-FDG-PET imaging allows the simultaneous assessment of metabolic activity in several tissues (e.g., brain, bone marrow) and is performed in conjunction with cross-sectional imaging that enables multi-organ structural assessments. Accordingly, 18F-FDG-PET/computed tomography (CT) imaging facilitates evaluation of disease pathways that span multiple organ systems. Within this paradigm, 18F-FDG-PET/CT imaging has been implemented to study the mechanism linking chronic stress to CVD. To evaluate this, stress-associated neural activity can be quantified (as metabolic activity of the amygdala (AmygA)), while leukopoietic activity, ArtI, and coronary plaque burden are assessed concurrently. Such simultaneous quantification of tissue structures and activities enables the evaluation of multi-organ pathways with the aid of mediation analysis. Using this approach, multi-system 18F-FDG-PET/CT imaging studies have demonstrated that chronically heightened stress-associated neurobiological activity promotes leukopoietic activity and systemic inflammation. This in turn fuels more ArtI and greater non-calcified coronary plaque burden, which result in more CVD events. Subsequent studies have revealed that common stressors, such as chronic noise exposure and income disparities, drive the front end of this pathway to increase CVD risk. Hence, multi-tissue multimodality imaging serves as a powerful tool to uncover complex disease mechanisms.



J Nucl Cardiol: 30 May 2021; 28:955-966
Osborne MT, Abohashem S, Zureigat H, Abbasi TA, Tawakol A
J Nucl Cardiol: 30 May 2021; 28:955-966 | PMID: 33205328
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Impact:
Abstract

Internal validation of myocardial flow reserve PET imaging using stress/rest myocardial activity ratios with Rb-82 and N-13-ammonia.

Juneau D, Wu KY, Kaps N, Yao J, ... Ruddy TD, deKemp RA
Background
Myocardial flow reserve (MFR) measurement provides incremental diagnostic and prognostic information. The objective of the current study was to investigate the application of a simplified model for the estimation of MFR using only the stress/rest myocardial activity ratio (MAR) in patients undergoing rest-stress cardiac PET MPI.
Methods and results
Rest and dipyridamole stress dynamic PET imaging was performed in consecutive patients using 82Rb or 13NH3 (n = 250 each). Reference standard MFR was quantified using a standard one-tissue compartment model. Stress/rest myocardial activity ratio (MAR) was calculated using the LV-mean activity from 2 to 6 minutes post-injection. Simplified estimates of MFR (MFREST) were then calculated using an inverse power function. For 13NH3, there was good correlation between MFR and MFREST values (R = 0.63), with similar results for 82Rb (R = 0.73). There was no bias in the MFREST values with either tracer. The overall diagnostic performance of MFREST for detection of MFR < 2 was good with ROC area under the curve (AUC) = 83.2 ± 1.2% for 13NH3 and AUC = 90.4 ± 0.7% for 82Rb.
Conclusion
MFR was estimated with good accuracy using 82Rb and 13NH3 with a simplified method that relies only on stress/rest activity ratios. This novel approach does not require dynamic imaging or tracer kinetic modeling. It may be useful for routine quality assurance of PET MFR measurements, or in scanners where full dynamic imaging and tracer kinetic modeling is not feasible for technical or logistical reasons.



J Nucl Cardiol: 30 May 2021; 28:835-850
Juneau D, Wu KY, Kaps N, Yao J, ... Ruddy TD, deKemp RA
J Nucl Cardiol: 30 May 2021; 28:835-850 | PMID: 33389638
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Impact:
Abstract

Assessing myocardial perfusion in suspected coronary artery disease: rationale and design of the second phase 3, open-label multi-center study of flurpiridaz (F-18) injection for positron emission tomography (PET) imaging.

Bourque JM, Hanson CA, Agostini D, Bateman TM, ... Udelson JE, Maddahi J
Background
Positron emission tomography (PET) myocardial perfusion imaging (MPI) with the novel radiopharmaceutical Fluorine-18 Flurpiridaz has been shown in Phase 1, 2, and first Phase 3 clinical studies to be safe and effective in diagnosing coronary artery disease (CAD). We describe the methodology of the second FDA-mandated phase 3 prospective, open-label, international, multi-center trial of F-18 Flurpiridaz PET MPI.
Methods
The primary study end point is to assess the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD [≥ 50% by quantitative invasive coronary angiography (ICA)] in patients with suspected CAD. The secondary endpoints are to evaluate the diagnostic efficacy of F-18 Flurpiridaz PET MPI compared to Tc-99 m-labeled SPECT MPI in the detection of CAD in all patients and in the following subgroups: (1) females; (2) patients with body mass index ≥ 30 kg/m2; and (3) diabetic patients. This trial\'s design differs from the first phase 3 trial in that (1) comparison to SPECT is now a secondary end point; (2) patients with known CAD are excluded; and (3) both SPECT and PET MPI are performed before ICA.
Conclusions
This second phase 3 study will provide additional evidence on the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD.
Trial registration number
NCT03354273.



J Nucl Cardiol: 30 May 2021; 28:1105-1116
Bourque JM, Hanson CA, Agostini D, Bateman TM, ... Udelson JE, Maddahi J
J Nucl Cardiol: 30 May 2021; 28:1105-1116 | PMID: 33521873
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Impact:
Abstract

The prevalence of TTR cardiac amyloidosis among patients undergoing bone scintigraphy.

Bianco M, Parente A, Biolè C, Righetti C, ... Anselmino M, Montagna L
Background
Radiolabeled bisphosphonates bone scintigraphy is highly sensitive in detecting transthyretin (TTR) cardiac amyloidosis; data on the true prevalence of cardiac involvement in TTR amyloidosis are lacking.
Methods and results
This retrospective observational, monocentric study aims to estimate the prevalence of positive bone scan suspect for TTR cardiac amyloidosis among an all-comers population who underwent a bone scintigraphy. ECG, echocardiography and clinical status of patients with unexpected cardiac uptake (Perugini score 2-3) who underwent bone scintigraphy with [99mTc]-HDP or [99mTc]-DPD at San Luigi Gonzaga University Hospital between January 2015 and May 2020 have been collected. The prevalence of bone scintigraphy suspect for cardiac involvement was 0.54% (23/4,228). The bone scintigraphy was mainly performed using [99mTc]-HDP (82.9%) and the dominant indication for the test was oncology in the 47.9% of cases. 8 Subjects had a history of neuropathy (34.8%) and 5 of carpal tunnel syndrome (21.7%). 11 Patients suffered a previous episode of heart failure (48%) while 5 patients (21.7%) were totally asymptomatic, without any sign or symptom before the bone scintigraphy making the nuclear examination crucial for an early diagnosis of TTR amyloidosis.
Conclusion
Bone scintigraphy allows suspecting TTR amyloidosis in a pre-clinical stage of the disease in an all-comers population of patients undergoing bone scintigraphy mainly for oncology reasons.



J Nucl Cardiol: 30 May 2021; 28:825-830
Bianco M, Parente A, Biolè C, Righetti C, ... Anselmino M, Montagna L
J Nucl Cardiol: 30 May 2021; 28:825-830 | PMID: 33728572
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Impact:
Abstract

Prognosis and recurrence in cardiac sarcoidosis: Serial assessment of BMIPP SPECT and FDG-PET.

Yamamoto A, Nagao M, Watanabe E, Imamura Y, ... Sakai S, Hagiwara N
Background
We analyzed 18F-Fludeoxyglucose positron emission tomography (FDG-PET) and 123I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) performed for cardiac sarcoidosis (CS) patients taking prednisolone, identified recurrence by FDG-PET, and investigated BMIPP as a recurrence and prognostic factor in CS.
Methods and results
CS patients who underwent BMIPP and FDG-PET within 2 months were enrolled. The recurrence-free group included patients with standardized uptake value (SUVmax) < 4 in the myocardium consecutively for ≥ 2 years. The total BMIPP SPECT defect score (BDS) was used to estimate myocardial damage. The predictability of the initial BDS and SUVmax for major adverse cardiac events (MACE) was analyzed using Kaplan-Meier analysis. Overall, 73 patients and 250 BMIPP and FDG-PET sets were analyzed retrospectively (mean follow-up, 3.5 years). The BDS was significantly greater for the recurrence group (N = 21) vs recurrence-free group (20 ± 13 vs 14 ± 12, P = 0.041). Patients with BDS ≥16 had a significantly higher MACE rate than patients with BDS < 16 (log-rank test, P = 0.016). However, MACE occurrence was comparable between patients with SUVmax ≥ 4 and < 4.
Conclusions
BDS is a predictive marker of recurrence and MACE. SUV is not related to MACE. Recurrence, defined by prednisolone treatment-induced SUV variability, was observed in approximately 30% of CS patients.



J Nucl Cardiol: 30 May 2021; 28:919-929
Yamamoto A, Nagao M, Watanabe E, Imamura Y, ... Sakai S, Hagiwara N
J Nucl Cardiol: 30 May 2021; 28:919-929 | PMID: 33728571
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Impact:
Abstract

Scan-rescan measurement repeatability of F-FDG PET/MR imaging of vascular inflammation.

Robson PM, Kaufman A, Pruzan A, Dweck MR, ... Fayad ZA, Mani V
Non-invasive positron emission tomography (PET) of vascular inflammation and atherosclerotic plaque by identifying increased uptake of 18F-fluordeoxyglucose (18F-FDG) is a powerful tool for monitoring disease activity, progression, and its response to therapy. 18F-FDG PET/computed tomography (PET/CT) of the aorta and carotid arteries has become widely used to assess changes in inflammation in clinical trials. However, the recent advent of hybrid PET/magnetic resonance (PET/MR) scanners has advantages for vascular imaging due to the reduction in radiation exposure and improved soft tissue contrast of MR compared to CT. Important for research and clinical use is an understanding of the scan-rescan repeatability of the PET measurement. While this has been studied for PET/CT, no data is currently available for vascular PET/MR imaging. In this study, we determined the scan-rescan measurement repeatability of 18F-FDG PET/MR in the aorta and carotid arteries was less than 5%, comparable to similar findings for 18F-FDG PET/CT.



J Nucl Cardiol: 26 May 2021; epub ahead of print
Robson PM, Kaufman A, Pruzan A, Dweck MR, ... Fayad ZA, Mani V
J Nucl Cardiol: 26 May 2021; epub ahead of print | PMID: 34046803
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Impact:
Abstract

Cardiac I-mIBG scintigraphy for prediction of catheter ablation outcome in patients with atrial fibrillation.

Sazonova SI, Varlamova JV, Nikitin NA, Minin SM, ... Popov SV, Romanov AB
Background
Previous studies show inconsistent results on the role of innervation imaging (with 123I-mIBG) in predicting late atrial fibrillation (AF) recurrence after catheter ablation (CA). These studies included patients with paroxysmal AF and studied prognostic value of post-CA I-123-mIBG parameters. Current study investigated the ability of pre CA 123-I-mIBG imaging to predict late AF recurrence in patients with persistent AF.
Methods
123I-mIBG cardiac imaging was performed before CA in 82 patients with persistent AF. Patient was followed for 12 months.
Results
Multivariable analysis demonstrated that late heart-to-mediastinum ratio (H/Mlate) and washout rate (WR) were independent predictors of AF recurrence. ROC-curve analysis data showed that H/Mlate <1.6 (sensitivity 73.53%, specificity 81.3%, AUC 0.792, P < .001) and WR > 25.11 (sensitivity 70.6%, specificity 70.8.3%, AUC 0.712, P < .001) indicate high probability of AF relapses during 12 months after CA.
Conclusion
Pre-CA parameters of global cardiac sympathetic activity estimated by 123I-mIBG scintigraphy are associated with late AF relapses in persistent AF patients with normal LVEF and absence of significant CAD.



J Nucl Cardiol: 26 May 2021; epub ahead of print
Sazonova SI, Varlamova JV, Nikitin NA, Minin SM, ... Popov SV, Romanov AB
J Nucl Cardiol: 26 May 2021; epub ahead of print | PMID: 34046802
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Impact:
Abstract

Polarity status of trigger signal during ECG-gating affects parameters of LV function in gated myocardial perfusion SPECT.

Qutbi M, Soltanshahi M, FarokhiMoghadam F, Ramandi FL, Kaghazchi F, Ahmadi R
Introduction:
and background
The polarity status is one of the important items of specifications of trigger signal from cardiac trigger monitors with two options, either positive or negative. Some systems allow the user to set the polarity of trigger signal before imaging. Efforts should be made to set the polarity status according to the recommendations provided by the manufacturers. In case of inappropriate selection, changes in computation of end-systolic and end-diastolic volumes as well as ejection fraction may occur.
Objective
To investigate the effect of the polarity status of trigger signals in synchronization process during 8- and 16-frame gated SPECT imaging on the systolic and diastolic parameters of LV function.
Methods
Thirty-four patients referred for a myocardial perfusion SPECT were consecutively included in the study. The rest scan for each patient was performed with 8- and 16-frame gating simultaneously with positive trigger signal set by the operator in a cardiac trigger monitor and then repeated after manual selection of negative polarity. In total, the 4 imaging modes acquired were 8-frame/positive-trigger, 16-frame/positive-trigger, 8-frame/negative-trigger, and 16-frame/negative-trigger. All SPECT images were reconstructed and processed with the same values of parameters. Systolic and diastolic indices of LV function were derived in QGS of the Cedars-Sinai software and then were compared using various statistical tests, and a reliability analysis was also performed.
Results
The age of patients recruited in the study was 58.41 ± 8.94, and 16 (47.1%) males and 18 (52.9%) females. All the correlation coefficients between corresponding parameters in positive and negative trigger signals were statistically significant. The difference between the parameters of systolic function including EF, EDV, and ESV in positive and negative trigger signals was statistically significant in paired sample t test. Likewise, a statistically significant difference was also found between mean phase angle in scans with positive and negative trigger signals by a phase difference of 147.91 (41.0% of an average cardiac cycle) and 149 (41.3% of an average cardiac cycle) degrees in 8- and 16-frame gating modes, respectively. Strong agreement (according to high values of intra-class correlation coefficient) was found for all four pairs. According to Bland-Altman results, an offset of about 3 percentage units was found, both between imaging in 8-frame gating compared to 16-frame gating, higher value in favor of 16-frame gating, and also between imaging with positive polarity trigger compared to negative-polarity trigger, again higher value in favor of positive-polarity triggering.
Conclusion
The status of the polarity of trigger signals or similar CTM-camera delays in synchronization process during 8- and 16-frame gated SPECT imaging can be considered as one of the factors that may influence systolic and diastolic indices of LV function.



J Nucl Cardiol: 24 May 2021; epub ahead of print
Qutbi M, Soltanshahi M, FarokhiMoghadam F, Ramandi FL, Kaghazchi F, Ahmadi R
J Nucl Cardiol: 24 May 2021; epub ahead of print | PMID: 34036529
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Impact:
Abstract

Myocardial blood flows and reserves on solid state camera: Correlations with coronary history and cardiovascular risk factors.

Ferenczi P, Couffinhal T, Mamou A, Mamou Y, ... Coste P, Pinaquy JB
Objectives
Study designed to test association between stress-induced myocardial blood flow (sMBF), resting MBF (rMBF), and MBF reserve (MFR) and coronary artery disease (CAD) in a population of CAD and non-coronary patients. Secondary objectives were to confront visual analysis and dynamic analysis and to explore potential association between MBF and several cardiovascular risk factors
Methods:
A total of 155 patients who underwent dynamic myocardial perfusion imaging on a CZT camera were included. sMBF, rMBF, and MFR were evaluated, and cardiovascular risk was assessed.
Results
Significantly lower total sMBF and MFR were observed in CAD patient vs non-CAD patient. In comparison with visual analysis, lower sMBF were found in pathologic territory, lower rMBF in necrotic territory and lower MFR in necrotic ones. A significant correlation between total sMBF, rMBF and diabetes was found.
Conclusion
sMBF and MFR as assessed on CZT gamma-cameras can be used to determine the coronary state. Low total sMBF might be an independent risk factor of coronaropathy. An inverse correlation was suggested between total sMBF and rMBF with diabetes.



J Nucl Cardiol: 24 May 2021; epub ahead of print
Ferenczi P, Couffinhal T, Mamou A, Mamou Y, ... Coste P, Pinaquy JB
J Nucl Cardiol: 24 May 2021; epub ahead of print | PMID: 34036528
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Impact:
Abstract

New criteria for the diagnosis of infective endocarditis using 18F-FDG PET/CT imaging.

Gazzilli M, Albano D, Lucchini S, Peli A, ... Bertagna F, Giubbini R
Objectives
The purpose of this study was to examine a qualitative scoring system and a semi-quantitative method of FDG-PET/CT imaging in the diagnosis of infective endocarditis (IE).
Methods
We retrospectively included 108 patients who underwent 18F-FDG-PET/CT for suspected IE. PET/CT scans were interpreted using a 4-point score (0 = no uptake; 1 = cardiac uptake < blood-pool activity; 2 = blood-pool < uptake < liver activity; 3 = uptake > liver) and semi-quantitatively using SUVmax and SUVmean of the suspected valve lesion, liver, spleen, and of the bone marrow (BM). BM and spleen SUVmean were normalized to the liver, and hypermetabolism (HSBM) was defined as a BM or spleen-to-liver ratio > 1.
Results
Comparing the score criteria results with the clinical final diagnosis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of qualitative criteria were 93%, 81%, 84%, 91%, and 87%, respectively. A definite IE was documented in 83% of patients showing HSBM and abnormal cardiac uptake, 44% with abnormal cardiac uptake, 28% with HSBM, and 10% with neither one.
Conclusion
The qualitative scoring system is helpful in the diagnosis of IE. The HSBM is an additional, reliable indirect sign of IE.



J Nucl Cardiol: 24 May 2021; epub ahead of print
Gazzilli M, Albano D, Lucchini S, Peli A, ... Bertagna F, Giubbini R
J Nucl Cardiol: 24 May 2021; epub ahead of print | PMID: 34036525
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Impact:
Abstract

Determination of [N-13]-ammonia extraction fraction in patients with coronary artery disease by calibration to invasive coronary and fractional flow reserve.

Nye JA, Piccinelli M, Hwang D, Cooke CD, ... Koo BK, Garcia EV
Background
This study presents a new extraction fraction (EF) model based on physiological measures of invasive coronary flow reserve (CFR) and fractional flow reserve (FFR) in patients with suspected coronary artery disease (CAD) and normal index microcirculatory resistance (IMR). To ascertain the clinical relevance of the new EFs, flow measurements using the newly patient-determined EFs were compared to flow measurements using traditional animal-determined EFs.
Methods
39 patients were retrospectively selected that included a total of 91 vascular territories with invasive coronary angiography physiological measures. [N-13]-ammonia dynamic rest/adenosine-stress PET imaging was conducted in all patients and absolute myocardial flow was estimated using four published compartmental models. The extraction fraction during hyperemic flow was iteratively estimated by maximizing the agreement between invasive CFR and FFR with the non-invasive analogs myocardial flow reserve (MFR) and relative flow reserve (RFR) at similar physiological states, respectively.
Results
Using the new patient-determined EFs, agreement between CFR vs MFR for Model 1 and 2 was moderate and poor for Model 3 and 4. All models showed moderate agreement for FFR vs RFR. When using published models of animal-determined EFs, agreement between CFR vs MFR remained moderate for Model 1 and 2, and poor for Model 3 and 4. Similarly, all models showed moderate agreement for FFR vs RFR using animal-determined EF values. None of the observed differences were statistically significant.
Conclusions
Flow measurements using extraction fraction correction for [N-13]-ammonia based on calibration to invasive intracoronary angiography physiological measures in patients with CAD were not discordant from those reported in the literature. Either patient-determined or traditional animal-determined EF correction, when used with the appropriate flow model, yields moderate agreement with invasive measurements of coronary flow reserve and fractional flow reserve.



J Nucl Cardiol: 24 May 2021; epub ahead of print
Nye JA, Piccinelli M, Hwang D, Cooke CD, ... Koo BK, Garcia EV
J Nucl Cardiol: 24 May 2021; epub ahead of print | PMID: 34036523
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Impact:
Abstract

Comparison of Cadmium Zinc Telluride ECG-gated SPECT equilibrium radionuclide angiocardiography to magnetic resonance imaging to measure right ventricular volumes and ejection fraction in patients with cardiomyopathy.

Apert A, Canu M, Jankowski A, Riou L, ... Djaileb L, Barone-Rochette G
Aims
The objective of this study was to determine the accuracy of right ventricular function (RVF) assessed by Cadmium Zinc Telluride ECG-gated SPECT equilibrium radionuclide angiocardiography (CZT-ERNA).
Methods and results
Twenty-one consecutive patients with cardiomyopathy (aged 54 ± 19 years; 62% male) were included. RV ejection fraction (EF) and volumes were analyzed by CZT-ERNA and compared with values obtained by cardiac magnetic resonance imaging (CMR). Mean values were not different between CZT-ERNA and MRI for RVEF (48.1 ± 10.4% vs 50.8 ± 10.0%; P = .23). Significant correlations (P < .0001) were observed between CZT-ERNA and MRI for RVEF, RV end-diastolic volume, and end-systolic volume (r = 0.81, r = 0.93, and r = 0.96, respectively). Bland-Altman analysis showed a mean difference (bias) between CZT-ERNA and MRI for RVEF of -2.69% (95% CI - 5.35 to - 0.42) with good agreement between the 2 techniques (limits of agreement, -14.3 to 8.99). Intraobserver and interobserver reproducibility of RVF measured by CZT-ERNA was high.
Conclusion
CZT-ERNA provides accurate, reproducible assessment of RVF and appears as a good alternative to cardiac magnetic resonance for the evaluation of the magnitude of RVF in patients with cardiomyopathy.



J Nucl Cardiol: 13 May 2021; epub ahead of print
Apert A, Canu M, Jankowski A, Riou L, ... Djaileb L, Barone-Rochette G
J Nucl Cardiol: 13 May 2021; epub ahead of print | PMID: 33988809
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Impact:
Abstract

Aortic wall segmentation in F-sodium fluoride PET/CT scans: Head-to-head comparison of artificial intelligence-based versus manual segmentation.

Piri R, Edenbrandt L, Larsson M, Enqvist O, ... Gerke O, Høilund-Carlsen PF
Background
We aimed to establish and test an automated AI-based method for rapid segmentation of the aortic wall in positron emission tomography/computed tomography (PET/CT) scans.
Methods
For segmentation of the wall in three sections: the arch, thoracic, and abdominal aorta, we developed a tool based on a convolutional neural network (CNN), available on the Research Consortium for Medical Image Analysis (RECOMIA) platform, capable of segmenting 100 different labels in CT images. It was tested on 18F-sodium fluoride PET/CT scans of 49 subjects (29 healthy controls and 20 angina pectoris patients) and compared to data obtained by manual segmentation. The following derived parameters were compared using Bland-Altman Limits of Agreement: segmented volume, and maximal, mean, and total standardized uptake values (SUVmax, SUVmean, SUVtotal). The repeatability of the manual method was examined in 25 randomly selected scans.
Results
CNN-derived values for volume, SUVmax, and SUVtotal were all slightly, i.e., 13-17%, lower than the corresponding manually obtained ones, whereas SUVmean values for the three aortic sections were virtually identical for the two methods. Manual segmentation lasted typically 1-2 hours per scan compared to about one minute with the CNN-based approach. The maximal deviation at repeat manual segmentation was 6%.
Conclusions
The automated CNN-based approach was much faster and provided parameters that were about 15% lower than the manually obtained values, except for SUVmean values, which were comparable. AI-based segmentation of the aorta already now appears as a trustworthy and fast alternative to slow and cumbersome manual segmentation.



J Nucl Cardiol: 11 May 2021; epub ahead of print
Piri R, Edenbrandt L, Larsson M, Enqvist O, ... Gerke O, Høilund-Carlsen PF
J Nucl Cardiol: 11 May 2021; epub ahead of print | PMID: 33982202
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Impact:
Abstract

Prospect of positron emission tomography for abdominal aortic aneurysm risk stratification.

Gandhi R, Bell M, Bailey M, Tsoumpas C
Abdominal aortic aneurysm (AAA) disease is characterized by an asymptomatic, permanent, focal dilatation of the abdominal aorta progressing towards rupture, which confers significant mortality. Patient management and surgical decisions rely on aortic diameter measurements via abdominal ultrasound surveillance. However, AAA rupture can occur at small diameters or may never occur at large diameters, implying that anatomical size is not necessarily a sufficient indicator. Molecular imaging may help identify high-risk patients through AAA evaluation independent of aneurysm size, and there is the question of the potential role of positron emission tomography (PET) and emerging role of novel radiotracers for AAA. Therefore, this review summarizes PET studies conducted in the last 10 years and discusses the usefulness of PET radiotracers for AAA risk stratification. The most frequently reported radiotracer was [18F]fluorodeoxyglucose, indicating inflammatory activity and reflecting the biomechanical properties of AAA. Emerging radiotracers include [18F]-labeled sodium fluoride, a calcification marker, [64Cu]DOTA-ECL1i, an indicator of chemokine receptor type 2 expression, and [18F]fluorothymidine, a marker of cell proliferation. For novel radiotracers, preliminary trials in patients are warranted before their widespread clinical implementation. AAA rupture risk is challenging to evaluate; therefore, clinicians may benefit from PET-based risk assessment to guide patient management and surgical decisions.



J Nucl Cardiol: 10 May 2021; epub ahead of print
Gandhi R, Bell M, Bailey M, Tsoumpas C
J Nucl Cardiol: 10 May 2021; epub ahead of print | PMID: 33977372
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Impact:
Abstract

Transthyretin Cardiac Amyloidosis Scintigraphy Using Planar D-SPECT on Dedicated Cardiac CZT Camera.

Tshori S, Livschitz S, Volodarsky I, Goland S, ... Fabrikant J, George J
Background
Bone scintigraphy is a main diagnostic tool in suspected ATTR patients. Almost all literature is based on conventional whole body gamma cameras, and there is very sparse data evaluating the use of dedicated cardiac CZT cameras. The aim of this study was to evaluate the utility of bone scintigraphy in suspected transthyretin cardiac amyloidosis (ATTR-CA) patients on a dedicated cardiac CZT camera.
Methods
Seventy-three patients with suspected ATTR-CA underwent planar and SPECT Tc-99 m pyrophosphate scintigraphy using dedicated cardiac CZT camera between May and August 2019.
Results
Planar D-SPECT image quality was mostly good. Six patients were identified as ATTR-CA positive. Inter-observer agreement based on both Perugini score and on planar D-SPECT H/CL ratio was excellent.
Conclusions
ATTR-CA scintigraphy using dedicated cardiac CZT camera was feasible, and yielded planar D-SPECT images with excellent inter-observer agreement.



J Nucl Cardiol: 10 May 2021; epub ahead of print
Tshori S, Livschitz S, Volodarsky I, Goland S, ... Fabrikant J, George J
J Nucl Cardiol: 10 May 2021; epub ahead of print | PMID: 33977371
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Impact:
Abstract

N-Ammonia myocardial blood flow quantitation in patient with aneurismal coronary artery disease.

Plata-Corona JC, Carvajal-Juarez I, Espinola-Zavaleta N, Damas-De Los Santos F, Rivera-Bravo B, Alexanderson-Rosas E
Aneurysmal coronary artery disease includes coronary artery aneurysms and ectasia; this condition has been associated with poor long-term outcomes. Few studies have explored myocardial blood flow 13N-ammonia PET/CT MPI added value. We present a 45-year-old man who came to the emergency department with chest pain. After a physical examination and laboratory studies, he was diagnosed with very high-risk unstable angina and referred to the catheterization laboratory. Coronary angiography showed the culprit lesion in the LCx and was treated by angioplasty and stent. LAD was found with coronary artery ectasia (TIMI 2 flow grade) and the RCA with aneurysmal disease in the proximal and middle segments (TIMI 3 flow grade). Medical treatment was decided for these findings and the patient was discharged. Two weeks later, we performed a 13N-ammonia PET/CT MPI founding apical, inferior, and inferoseptal severe ischemia, and reduced hyperemic coronary blood flow and coronary flow reserve in the RCA territory. Flow was normal in the LAD territory. Although coronary angiography remains the gold standard for evaluating these coronary abnormalities, it does not show the physiological compromise. Therefore 13N-ammonia PET/CT MPI should be performed as a complementary noninvasive imaging approach.



J Nucl Cardiol: 05 May 2021; epub ahead of print
Plata-Corona JC, Carvajal-Juarez I, Espinola-Zavaleta N, Damas-De Los Santos F, Rivera-Bravo B, Alexanderson-Rosas E
J Nucl Cardiol: 05 May 2021; epub ahead of print | PMID: 33959843
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Impact:
Abstract

Intravenous insulin injection supplemented with subsequent milk consumption is a safer formulation for cardiac viability F-FDG imaging.

Chen YC, Pan MJ, Wang QQ, Wang YH, Zhuo HL, Dai RZ
Background
The safety and efficacy of intravenous insulin injection coupled with subsequent milk consumption was evaluated for high-quality cardiac viability F-18-fluorodeoxyglucose (18F-FDG) images.
Methods and results
A total of 328 patients with known/suspected coronary artery disease received intravenous insulin injection with or without subsequent milk consumption for cardiac 18F-FDG imaging. When blood glucose levels had decreased by ≥ 20%, 18F-FDG was injected. Patients were scored for hypoglycemic symptoms using a 10-point scale (discomfort: 0, none; 1 to 3, mild; 4 to 6, moderate; 7 to 9, severe). An insulin-related hypoglycemic event was defined as an increased symptomatic score following insulin injection. The number of hypoglycemic events was significantly lower in the milk consumption group than in the group that did not (24/164 vs. 51/164, P < .01). Maximal and averaged standardized uptake value of the left ventricular myocardium (MyoSUVmax and MyoSUVmean) were also measured. The milk and control groups had similar mean hypoglycemic symptom scores (4.2 ± 4.0 vs. 3.3 ± 3.1, respectively), MyoSUVmax, and MyoSUVmean (11.1 ± 4.8, 7.3 ± 3.2 vs. 11.4 ± 4.5, 7.4 ± 3.2, respectively).
Conclusion
Intravenous insulin injection supplemented with subsequent milk consumption is a safer formulation for cardiac viability 18F-FDG imaging without impairing image quality.



J Nucl Cardiol: 04 May 2021; epub ahead of print
Chen YC, Pan MJ, Wang QQ, Wang YH, Zhuo HL, Dai RZ
J Nucl Cardiol: 04 May 2021; epub ahead of print | PMID: 33954874
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Impact:
Abstract

Assessment of a digital and an analog PET/CT system for accurate myocardial perfusion imaging with a flow phantom.

Siekkinen R, Kirjavainen AK, Koskensalo K, Smith NAS, ... Teräs M, Teuho J
In Myocardial Perfusion Imaging (MPI) with Positron Emission Tomography/Computed Tomography (PET/CT) systems, accurate quantification is essential. We assessed flow quantification accuracy over various injected activities using a flow phantom.
Methods
The study was performed on the digital 4-ring Discovery MI (DMI-20) and analog Discovery 690 (D690) PET/CT systems, using 325-1257 MBq of [15O]H2O. PET performance and flow quantification accuracy were assessed in terms of count-rates, dead-time factors (DTF), scatter fractions (SF), time-activity curves (TACs), areas-under-the-curves (AUCs) and flow values.
Results
On DMI-20, prompts of 12.8 Mcps, DTF of 2.06 and SF of 46.1% were measured with 1257 MBq of activity. On the D690, prompts of 6.85 Mcps, DTF of 1.57 and SF of 32.5% were measured with 1230 MBq of activity. AUC values were linear over all activities. Mean wash-in flow error was - 9% for both systems whereas wash-out flow error was - 5% and - 6% for DMI-20 and D690. With the highest activity, wash-out flow error was - 12% and - 7% for the DMI-20 and D690.
Conclusion
DMI-20 and D690 preserved accurate flow quantification over all injected activities, with maximum error of - 12%. In the future, flow quantification accuracy over the activities and count-rates evaluated in this study should be assessed.



J Nucl Cardiol: 03 May 2021; epub ahead of print
Siekkinen R, Kirjavainen AK, Koskensalo K, Smith NAS, ... Teräs M, Teuho J
J Nucl Cardiol: 03 May 2021; epub ahead of print | PMID: 33948894
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Impact:
Abstract

Diagnostic accuracy of myocardial perfusion imaging in patients evaluated for kidney transplantation: A systematic review and meta-analysis.

Kelderman JR, Jolink FEJ, Benjamens S, Monroy-Gonzalez AG, Pol RA, Slart RHJA
Background
Cardiovascular disease is the most common cause of death after kidney transplantation. Coronary artery disease (CAD) assessment is therefore mandatory in patients evaluated for transplantation. We aimed to assess the diagnostic accuracy for CAD of single-photon emission computed tomography (SPECT) compared to the standards invasive coronary angiography (ICA) and coronary computed tomography angiography (CCTA) in patients evaluated for kidney transplantation.
Methods
We performed a systematic literature search in PubMed, EMBASE, Web of Science, OvidSP (Medline), The Cochrane Library and Google Scholar. Studies investigating the diagnostic accuracy of myocardial perfusion imaging (MPI) SPECT in patients evaluated for kidney transplantation were retrieved. After a risk of bias assessment using QUADAS-2, a meta-analysis was conducted.
Results
Out of 1459 records, 13 MPI SPECT studies were included in the meta-analysis with a total of 1245 MPI SPECT scans. There were no studies available with CCTA as reference. Pooled sensitivity of MPI SPECT for CAD was 0.66 (95% CI 0.53 to 0.77), pooled specificity was 0.75 (95% CI 0.63 to 0.84) and the area under the curve (AUC) was 0.76. Positive likelihood ratio was 2.50 (95% CI 1.78 to 3.51) and negative likelihood ratio was 0.41 (95% CI 0.28 to 0.61). Pooled positive predictive value was 64.9% and pooled negative predictive value was 74.1%. Significant heterogeneity existed across the included studies.
Conclusions
MPI SPECT had a moderate diagnostic accuracy in patients evaluated for kidney transplantation, with a high rate of false-negative findings. The use of an anatomical gold standard against a functional imaging test in the included studies is however suboptimal.



J Nucl Cardiol: 03 May 2021; epub ahead of print
Kelderman JR, Jolink FEJ, Benjamens S, Monroy-Gonzalez AG, Pol RA, Slart RHJA
J Nucl Cardiol: 03 May 2021; epub ahead of print | PMID: 33948891
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Impact:
Abstract

Visual patterns of breast attenuation artifacts in women and men with an upright and supine cadmiun-zinc-telluride camera.

Waqar F, Athar MW, Dwivedi AK, Ahmad S, ... Khan N, Gerson MC
Background
Breast attenuation artifacts occurring with upright cadmium-zinc-telluride (CZT) cardiac imaging systems have not been well characterized.
Methods
216 consecutive patients with Single Photon Emission Computerized Tomography myocardial perfusion imaging and no angiographically significant obstructive coronary artery disease were identified. All upright and supine SPECT images as well as coronary angiograms were reviewed and analyzed in blinded fashion.
Results
In women imaged upright, more visual false positive defects were noted in the inferior wall compared to the anterior wall (26 vs. 10 at rest, p = 0.006, and 33 vs. 13 at stress, p < 0.001). Visual inferior wall defects were more common in the upright than supine position at stress (33 vs. 23, p = 0.018) and rest (26 vs. 14, p = 0.011), and most apparent in non-obese women (13 vs. 8, at stress, p = 0.059 and 11 vs. 5, at rest, p = 0.014).
Conclusions
With upright CZT myocardial perfusion imaging, women often have visible inferior wall attenuation artifact defects, likely from pendant breast tissue. These inferior wall attenuation artifacts may be seen in non-obese female patients.



J Nucl Cardiol: 03 May 2021; epub ahead of print
Waqar F, Athar MW, Dwivedi AK, Ahmad S, ... Khan N, Gerson MC
J Nucl Cardiol: 03 May 2021; epub ahead of print | PMID: 33948890
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Impact:
Abstract

Subacute myocardial infarction detected by technetium-99m-labeled somatostatin analog scintigraphy.

Sazonova SI, Syrkina AG, Mochula OV, Anashbaev ZZ, Popov EV, Ryabov VV
Recently, the applicability of somatostatin receptor-targeted (SSTR-t) radiotracers for post-ischemic myocardial inflammation imaging has been shown using PET. Currently, there are no studies which demonstrate ability of SPECT and technetium-99m SSTR-t radiotracers to detect inflammation, which appears in response to acute myocardial infarction (AMI). A case of 51-year-old male with acute anterior myocardial infarction (AMI) with ST elevation has been presented. This patient on 7th day after AMI onset underwent SPECT/CT (by cardiac cadmium-zinc-telluride gamma-camera) with 99mTc-Tectrotide, cardiac MRI with gadolinium and, on 9th day after AMI, myocardial perfusion scintigraphy (MPS) at rest. Clear myocardial uptake of 99mTc-Tectrotide, predominantly in apical and intermediate anterior wall of left ventricle was detected. The uptake matched with areas of hypoperfusion (by SPECT) and myocardial injury (by MRI). This case demonstrated the applicability of technetium-99m-labeled SSTR-t radiotracers for post-infarction inflammation imaging. Currently assumed, that SSTR-t radiotracers reflect an increased number of activated macrophages infiltrating infarcted myocardium, which is not possible using any other imaging technique. Thus, potentially, SSTR scintigraphy may be useful for diagnosis and monitoring of myocardial post-infarction inflammation as well as for anti-inflammatory image-guide therapy assessment.



J Nucl Cardiol: 29 Apr 2021; epub ahead of print
Sazonova SI, Syrkina AG, Mochula OV, Anashbaev ZZ, Popov EV, Ryabov VV
J Nucl Cardiol: 29 Apr 2021; epub ahead of print | PMID: 33939163
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Impact:
Abstract

The current status of CZT SPECT myocardial blood flow and reserve assessment: Tips and tricks.

Zavadovsky KV, Mochula AV, Maltseva AN, Shipulin VV, ... Liga R, Gimelli A
Cardiac PET-derived measurements of myocardial blood flow (MBF) and myocardial flow reserve (MFR) are proven robust indexes of the severity of coronary artery disease (CAD). They facilitate the diagnosis of diffuse epicardial and microvascular disease and are also of prognostic significance. However, low availability and high cost have limited their wide clinical implementation. Over the last 15 years, cadmium zinc telluride (CZT)-based detectors have been implemented into SPECT imaging devices. Myocardial perfusion scintigraphy can be performed faster and with less radiation exposure as compared with standard gamma cameras. Rapid dynamic SPECT studies with higher count rates can be performed. This technological breakthrough has renewed the interest in SPECT MBF assessment in patients with CAD. Currently, two cardiac-centered CZT gamma cameras are available commercially-Discovery NM530c and D-SPECT. They differ in parameters such as collimator design, number of detectors, sensitivity, spatial resolution and image reconstruction. A number of publications have focused on the feasibility of dynamic CZT SPECT and on the correlation with cardiac PET and invasive coronary angiography measurements of fractional flow reserve. Current study reviews the present status of MBF and MFR assessment with CZT SPECT. It also aims to provide an overview of specific issues related to acquisition, processing and interpretation of quantitative studies in patients with CAD.



J Nucl Cardiol: 29 Apr 2021; epub ahead of print
Zavadovsky KV, Mochula AV, Maltseva AN, Shipulin VV, ... Liga R, Gimelli A
J Nucl Cardiol: 29 Apr 2021; epub ahead of print | PMID: 33939162
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Impact:
Abstract

Prediction of 2-year major adverse cardiac events from myocardial perfusion scintigraphy and clinical risk factors.

Leslie WD, Bryanton M, Goertzen A, Slomka P
Background
We developed CRAX2MACE, a new tool derived from clinical and SPECT myocardial perfusion imaging (MPI) variables, to predict 2-year probability of major adverse cardiac event (MACE) comprising death, hospitalized acute myocardial infarction or coronary revascularization.
Methods
Consecutive individuals with SPECT MPI 2001-2008 had two-year MACE determined from population-based health services data. CRAX2MACE included age, sex, diabetes, recent cardiac hospitalization, pharmacologic stress, stress total perfusion deficit (TPD), ischemic (stress-rest) TPD, left ventricular ejection fraction and transient ischemic dilation ratio. Two-year event rates were classified as low (< 5%), moderate (5.0-9.9%), high (10-19.9%) and very high (20% or greater).
Results
The study population comprised 3896 individuals for the development and 1946 for the validation subgroups with subsequent MACE in 589 (15.1%) and 272 (14.0%), respectively. CRAX2MACE, derived from the development subgroups, accurately stratified MACE risk in the validation subgroup (area under the receiver operating characteristics curve 0.79) with stepwise increase in the observed event rate with increasing predicted risk category (low, 2.3%; moderate, 5.5%; high, 18.8%; very high 33.2%; P-trend < 0.001).
Conclusions
A simple tool based upon clinical risk factors and MPI variables predicts 2-year cardiac events. Risk stratification between the low and very high groups was greater than tenfold.



J Nucl Cardiol: 27 Apr 2021; epub ahead of print
Leslie WD, Bryanton M, Goertzen A, Slomka P
J Nucl Cardiol: 27 Apr 2021; epub ahead of print | PMID: 33913097
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Impact:
Abstract

Stress testing and myocardial perfusion imaging for patients after recovery from severe COVID-19 infection requiring hospitalization: A single-center experience.

Hasnie UA, Hawi R, Andrikopoulou E, Iskandrian AE, Hage FG
Background
As the coronavirus pandemic progresses, patients that have recovered from COVID-19-related hospitalization require resumption of care for other medical issues. Thus far, the literature has not detailed the experience of stress testing in this patient population.
Methods
We retrospectively reviewed patients that recovered from COVID-19-related hospitalizations and underwent SPECT MPI studies at the University of Alabama at Birmingham Medical Center.
Results
15 patients (median age 60 years, 67% male) were identified with COVID-19-related hospitalization and then underwent SPECT MPI imaging after recovery. During COVID-19-related hospitalization (median length of stay 8 days), patients received various COVID-19 therapies; 3 required mechanical ventilation. Stress tests (4 Exercise, 11 Pharmacologic) were performed 65 days (interquartile range 31-94 days) after the diagnosis of COVID-19. None of the patients experienced serious adverse events during or after stress testing. One patient required regadenoson reversal using aminophylline due to chest pain.
Conclusion
Over time, more patients that recover from COVID-19 infection will require MPI testing for myocardial ischemia evaluation. Our study provides some information regarding performing stress testing in patients who have recently recovered from COVID-19 infections requiring hospitalization. Further studies are recommended to establish formal protocols for testing in this cohort.



J Nucl Cardiol: 25 Apr 2021; epub ahead of print
Hasnie UA, Hawi R, Andrikopoulou E, Iskandrian AE, Hage FG
J Nucl Cardiol: 25 Apr 2021; epub ahead of print | PMID: 33904148
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Impact:
Abstract

Reduced acquisition time for thallium myocardial perfusion imaging with large field cadmium-zinc-telluride SPECT/CT cameras: An equivalence study.

Bonnefoy PB, Janvier L, Arede C, Drouet C, ... Marque S, Ahond-Vionnet R
Background
Cadmium-zinc-telluride (CZT) SPECT/CT cameras with large field of view offer a higher sensitivity than conventional Anger cameras. This prospective study aimed to determine the equivalence between a conventional protocol and a reduced acquisition time protocol for 201-Thallium myocardial perfusion imaging (MPI) using a whole-body CZT SPECT camera.
Methods and results
Stress MPI was obtained for 103 consecutive patients on a DISCOVERY-CZT camera. Images were anonymized and post-processed to simulate a 25% (D75 dataset) and 50% (D50 dataset) decrease in total recorded counts. Concerning the number of segments displaying a tracer uptake < 70% of maximum intensity per patient, equivalence was demonstrated for both count-reduced datasets with a good inter-observer agreement (between 0.90 and 0.88). When comparing the full-vs-D75 datasets and full-vs-D50 datasets, mean difference was 0.06 segment (CI95: [- 0.15;0.27], P < 0.001) and 0.518 segment (CI95: [0.28;0.76], P < 0.001) respectively. Inter-observer agreement was also moderate to good concerning the number of pathological segments (between 0.6 and 0.7) and excellent for functional parameters.
Conclusion
Whole-body CZT SPECT/CT cameras allow to reduce 201-Thallium MPI injected activity or acquisition time by 50% with an equivalence in the number of segments displaying a tracer uptake < 70% of maximum intensity and with a good inter-observer agreement.



J Nucl Cardiol: 21 Apr 2021; epub ahead of print
Bonnefoy PB, Janvier L, Arede C, Drouet C, ... Marque S, Ahond-Vionnet R
J Nucl Cardiol: 21 Apr 2021; epub ahead of print | PMID: 33890184
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Impact:
Abstract

Cardiac amyloidosis characterization by kinetic model fitting on [18F]florbetaben PET images.

Santarelli MF, Genovesi D, Scipioni M, Positano V, ... Emdin M, Marzullo P
Objective
To evaluate the feasibility of kinetic modeling-based approaches from [18F]-Flobetaben dynamic PET images as a non-invasive diagnostic method for cardiac amyloidosis (CA) and to identify the two AL- and ATTR-subtypes.
Methods and results
Twenty-one patients with diagnoses of CA (11 patients with AL-subtype and 10 patients with ATTR-subtype of CA) and 15 Control patients with no-CA conditions underwent PET/CT imaging after [18F]Florbetaben bolus injection. A two-tissue-compartment (2TC) kinetic model was fitted to time-activity curves (TAC) obtained from left ventricle wall and left atrium cavity ROIs to estimate kinetic micro- and macro-parameters. Combinations of kinetic parameters were evaluated with the purpose of distinguishing Control subjects and CA patients, and to correctly label the last ones as AL- or ATTR-subtype. Resulting sensitivity, specificity, and accuracy for Control subjects were: 0.87, 0.9, 0.89; as far as CA patients, the sensitivity, specificity, and accuracy were respectively 0.9, 1, and 0.97 for AL-CA patients and 0.9, 0.92, 0.97 for ATTR-CA patients.
Conclusion
Pharmacokinetic analysis based on a 2TC model allows cardiac amyloidosis characterization from dynamic [18F]Florbetaben PET images. Estimated model parameters allows to not only distinguish between Control subjects and patients, but also between AL- and ATTR-amyloid patients.



J Nucl Cardiol: 15 Apr 2021; epub ahead of print
Santarelli MF, Genovesi D, Scipioni M, Positano V, ... Emdin M, Marzullo P
J Nucl Cardiol: 15 Apr 2021; epub ahead of print | PMID: 33864226
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Impact:
Abstract

Imaging of cardiac fibroblast activation in a patient after acute myocardial infarction using Ga-FAPI-04.

Notohamiprodjo S, Nekolla SG, Robu S, Villagran Asiares A, ... Weber WA, Varasteh Z
Our previous study has demonstrated the feasibility of noninvasive imaging of fibroblast activation protein (FAP)-expression after myocardial infarction (MI) in MI-territory in a rat model with 68Ga-FAPI-04-PET. In the current extended clinical case, we sought to delineate cardiac uptake of 68Ga-FAPI-04 in a patient after MI with clinical indication for the evidence of fibroblast activation. Carcinoma patients without cardiac disease underwent 68Ga-FAPI-04-PET/CT as control. The patient with one-vessel disease underwent dynamic 68Ga-FAPI-04-cardiac-PET/CMR for 60 minutes. Correlation of cardiac 68Ga-FAPI-04 uptake with clinical findings, ECG, echocardiography, coronary-arteriography and enhanced cardiac-MRI with T1 MOLLI and ECV mapping were performed. No uptake was found in normal myocardium and in mature scar. A focal intense 68Ga-FAPI-04 uptake with continuous wash-out in the infarct territory of coronary occlusion correlating with T1 and ECV mapping was observed. The uptake of 68Ga-FAPI-04 extends beyond the actual infarcted area and overestimates the infarct size as confirmed by follow-up CMR.



J Nucl Cardiol: 14 Apr 2021; epub ahead of print
Notohamiprodjo S, Nekolla SG, Robu S, Villagran Asiares A, ... Weber WA, Varasteh Z
J Nucl Cardiol: 14 Apr 2021; epub ahead of print | PMID: 33860458
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Impact:
Abstract

Predictive value of incidental right ventricular abnormalities identified on SPECT for mortality and pulmonary hypertension.

Jose A, Zhou C, Baker R, Walker J, ... Elwing JM, Gerson M
Background
The clinical significance of incidentally found RV abnormalities on low-risk SPECT studies is not well-defined. The objective of this study was to determine the predictive value of incidental right ventricular (RV) abnormalities identified on single photon emission computed tomography (SPECT) scans for mortality and pulmonary hypertension (PH).
Methods
We retrospectively analyzed all low-risk SPECT studies in patients without known coronary artery or pulmonary vascular disease, performed at our institution, from 2007-2020. Adjusted Cox proportional hazards models were used to evaluate the association between incidental RV abnormalities on low-risk SPECT studies and outcomes.
Results
Of the 4761 patients included in the analysis, mortality events were present in 494, and echocardiographic PH was present in 619. Incidental RV abnormalities on low-risk SPECT studies were significantly and independently associated with all-cause mortality (HR = 1.41, CI [1.07-1.86], P = 0.0152) and echocardiographic PH (HR = 2.06, CI [1.64-2.60], P < 0.0001).
Conclusions
These data suggest incidental RV abnormalities found on low-risk SPECT imaging studies are significantly and independently associated with increased mortality and risk of developing echocardiographic PH, and could identify high-risk patients for closer monitoring and additional diagnostic testing.



J Nucl Cardiol: 12 Apr 2021; epub ahead of print
Jose A, Zhou C, Baker R, Walker J, ... Elwing JM, Gerson M
J Nucl Cardiol: 12 Apr 2021; epub ahead of print | PMID: 33851355
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Impact:
Abstract

Clinical impact of quantitative [O] HO PET/CT myocardial perfusion imaging on decision-making regarding invasive management of coronary artery disease.

Promteangtrong C, Jantarato A, Kunawudhi A, Kiatkittikul P, ... Boonkawin N, Chotipanich C
Background
This study was performed to determine the impact of oxygen-15-labeled water ([15O] H2O) positron emission tomography/computed tomography (PET/CT) myocardial perfusion imaging (MPI) on referral for invasive coronary angiography (ICA) and revascularization.
Methods
This study involved 57 patients who underwent [15O] H2O PET/CT MPI for evaluation of coronary artery disease (CAD). Data of referral for ICA and revascularization, clinical symptoms, and cardiac events within 6 months after MPI were assessed. Logistic regression was used to determine the predictors for referral and revascularization. The diagnostic values of hyperemic myocardial blood flow (MBF) and coronary flow reserve (CFR) were calculated.
Results
Normal and abnormal MPI findings were observed in 18 (32%) and 39 (68%) patients, respectively. The referral rate was significantly different between the normal and abnormal MPI groups (5.6% and 48.7%, respectively; P = .002). Revascularization rate of abnormal MPI group was 40.0%. There were significant differences of hyperemic MBF and CFR between patients with and without referral. Hyperemic MBF was significant predictor for referral (OR 15.24, 95% CI 3.39-68.55, P < .005) and revascularization (OR 28.57, 95% CI 3.08-265.33, P < .005).
Conclusion
[15O] H2O PET/CT MPI showed a clinical impact on decision-making regarding invasive procedure for management of CAD.



J Nucl Cardiol: 05 Apr 2021; epub ahead of print
Promteangtrong C, Jantarato A, Kunawudhi A, Kiatkittikul P, ... Boonkawin N, Chotipanich C
J Nucl Cardiol: 05 Apr 2021; epub ahead of print | PMID: 33826128
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Impact:
Abstract

Cardiac microcalcification burden: Global assessment in high cardiovascular risk subjects with Na[F]F PET-CT.

Borges-Rosa J, Oliveira-Santos M, Silva R, da Silva NP, ... Gonçalves L, Ferreira MJ
Background
Fluorine-18 sodium fluoride (Na[18F]F) atherosclerotic plaque uptake in positron emission tomography with computed tomography (PET-CT) identifies active microcalcification. We aim to evaluate global cardiac microcalcification activity with Na[18F]F, as a measure of unstable microcalcification burden, in high cardiovascular (CV) risk patients.
Methods and results
Thirty-four high CV risk individuals without previous CV events were scanned with Na[18F]F PET-CT. Cardiac Na[18F]F uptake was assessed through the global molecular calcium score (GMCS), which was calculated by summing the product of the mean standardized uptake value times the area of the cardiac regions of interest times the slice thickness for all cardiac transaxial slices, divided by the total number of slices. Mean age is 63.5 ± 7.8 years and 62% male. Median GMCS is 320.9 (240.8-402.8). Individuals with more than five CV risk factors (50%) have increased GMCS [356.7 (321.0-409.6) vs. 261.1 (225.6-342.1), P = 0.01], which is positively correlated with predicted fatal CV risk by SCORE (rs = 0.32, P = 0.04). There is a positive correlation between GMCS and weight (rs = 0.61), body mass index (rs = 0.66), abdominal perimeter (rs = 0.74), thoracic fat volume (rs = 0.47), and epicardial adipose tissue (rs = 0.41), all with P ≤ 0.01. There is no correlation between GMCS and coronary calcium score nor coronary artery wall Na[18F]F uptake.
Conclusions
In a high CV risk group, the global cardiac microcalcification burden is related to CV risk factors, metabolic syndrome variables and cardiac fat. Cardiac GMCS is a promising risk stratification tool, combining a straightforward and objective methodology with a comprehensive analysis of both coronary and valvular microcalcification.



J Nucl Cardiol: 05 Apr 2021; epub ahead of print
Borges-Rosa J, Oliveira-Santos M, Silva R, da Silva NP, ... Gonçalves L, Ferreira MJ
J Nucl Cardiol: 05 Apr 2021; epub ahead of print | PMID: 33826127
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Impact:
Abstract

3D fusion between fluoroscopy angiograms and SPECT myocardial perfusion images to guide percutaneous coronary intervention.

Tang H, Bober RR, Zhao C, Zhang C, ... Xu Z, Zhou W
Background
Percutaneous coronary intervention (PCI) in stable coronary artery disease (CAD) is commonly triggered by abnormal myocardial perfusion imaging (MPI). However, due to the possibilities of multivessel disease, serial stenoses and variability of coronary artery perfusion distribution, an opportunity exists to better align anatomic stenosis with perfusion abnormalities to improve revascularization decisions. This study aims to develop a multi-modality fusion approach to assist decision-making for PCI.
Methods and results
Coronary arteries from fluoroscopic angiography (FA) were reconstructed into 3D artery anatomy. Left ventricular (LV) epicardial surface was extracted from SPECT. The artery anatomy and epicardial surface were non-rigidly fused. The accuracy of the 3D fusion was evaluated via both computer simulation and real patient data. Simulated FA and MPI were integrated and then compared with the ground truth from a digital phantom. The distance-based mismatch errors between simulated fluoroscopy and phantom arteries were 1.86 ± 1.43 mm for left coronary arteries (LCA) and 2.21 ± 2.50 mm for right coronary arteries (RCA). FA and SPECT images in 30 patients were integrated and then compared with the ground truth from CT angiograms. The distance-based mismatch errors between the fluoroscopy and CT arteries were 3.84 ± 3.15 mm for LCA and 5.55 ± 3.64 mm for RCA. The presence of the corresponding fluoroscopy and CT arteries in the AHA-17-segment model agreed well with a Kappa value of 0.91 (CI 0.89-0.93) for LCA and a Kappa value of 0.80 (CI 0.67-0.92) for RCA.
Conclusions
Our fusion approach is technically accurate to assist PCI decision-making and is clinically feasible to be used in the catheterization laboratory. Future studies are necessary to determine if fusion improves PCI-related outcomes.



J Nucl Cardiol: 05 Apr 2021; epub ahead of print
Tang H, Bober RR, Zhao C, Zhang C, ... Xu Z, Zhou W
J Nucl Cardiol: 05 Apr 2021; epub ahead of print | PMID: 33825145
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Abstract

Cardiac imaging for the assessment of patients being evaluated for liver transplantation.

Kassab K, Doukky R
Cardiac risk assessment prior to liver transplantation has become widely accepted. With the emergence of nonalcoholic steatohepatitis among the leading causes of end-stage liver disease and the steady rise of the age of liver transplant recipients, the burden of cardiovascular diseases has markedly increased in this population. Selecting appropriate liver transplant candidates is crucial due to the increasing demand for scarce donor organs. The use of noninvasive cardiac imaging for pre-operative assessment of the cardiovascular status of liver transplant recipients has been on the rise, yet the optimal assessment strategy remains an area of active debate. In this review, we examine the relevant literature pertaining to the diagnostic and prognostic applications of noninvasive cardiac imaging in this population. We also propose a simple literature-based evaluation algorithm for CAD surveillance in liver transplant candidates.



J Nucl Cardiol: 05 Apr 2021; epub ahead of print
Kassab K, Doukky R
J Nucl Cardiol: 05 Apr 2021; epub ahead of print | PMID: 33825142
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Abstract

The effect of Vitamin-K and Colchicine on Vascular Calcification Activity in subjects with Diabetes Mellitus (ViKCoVaC): A double-blind 2x2 factorial randomized controlled trial.

Bellinge JW, Francis RJ, Lee SC, Vickery A, ... Watts GF, Schultz CJ
Background
There is currently no treatment for attenuating progression of arterial calcification. 18F-sodium fluoride positron emission tomography (18F-NaF PET) locates regions of calcification activity. We tested whether vitamin-K1 or colchicine affected arterial calcification activity.
Methods
154 patients with diabetes mellitus and coronary calcification, as detected using computed tomography (CT), were randomized to one of four treatment groups (placebo/placebo, vitamin-K1 [10 mg/day]/placebo, colchicine [0.5 mg/day]/placebo, vitamin-K1 [10 mg/day]/ colchicine [0.5 mg/day]) in a double-blind, placebo-controlled 2x2 factorial trial of three months duration. Change in coronary calcification activity was estimated as a change in coronary maximum tissue-to-background ratio (TBRmax) on 18F-NaF PET.
Results
149 subjects completed follow-up (vitamin-K1: placebo = 73:76 and colchicine: placebo = 73:76). Neither vitamin-K1 nor colchicine had a statistically significant effect on the coronary TBRmax compared with placebo (mean difference for treatment groups 0·00 ± 0·16 and 0·01 ± 0·17, respectively, p > 0.05). There were no serious adverse effects reported with colchicine or vitamin-K1.
Conclusions
In patients with type 2 diabetes, neither vitamin-K1 nor colchicine significantly decreases coronary calcification activity, as estimated by 18F-NaF PET, over a period of 3 months.
Clinical trial registration
ACTRN12616000024448.



J Nucl Cardiol: 05 Apr 2021; epub ahead of print
Bellinge JW, Francis RJ, Lee SC, Vickery A, ... Watts GF, Schultz CJ
J Nucl Cardiol: 05 Apr 2021; epub ahead of print | PMID: 33825140
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Abstract

Impact of Gd-153 scanning line source attenuation correction on downstream invasive testing.

Singhvi A, Suacier S, Verma I, Felpel K, ... McMahon S, Duvall WL
Background
Attenuation correction (AC) using hardware and software solutions has been shown to increase the specificity of SPECT MPI by decreasing false positive results and improving prognostic ability. Theoretically this should reduce downstream testing and unnecessary costs. We sought to assess the consequences of the use of Gd-153 scanning line source attenuation correction during SPECT myocardial perfusion imaging (MPI) on downstream invasive testing.
Methods
All patients who underwent a clinically indicated Tc-99m stress SPECT MPI study from 2013 to 2015 at five hospitals (2 with AC and 3 without) were retrospectively reviewed. Patient demographics, results of testing, subsequent coronary angiography within 3 months, and revascularization were recorded. The results of the MPI studies, downstream angiogram utilization, and results of angiography were compared and a propensity matched subgroup analysis was performed.
Results
A total of 9968 patients underwent SPECT MPI during the study time period (6106 performed with AC and 3862 without). Out of 3928 patients included in the propensity matched cohort, there was no difference in the proportion of abnormal MPI results between the two groups (31.5% vs 30.4%, P = 0.47), however, more patients underwent coronary angiography within 90 days in the AC group (10.6% vs 8.7%, P = 0.05). There was no significant difference in the proportion of patients with angiographically significant obstructive disease (53.4% vs 56.1%, P = 0.19), however, fewer patients in the AC group with obstructive coronary disease were revascularized (36.1% vs 46.8%, P = 0.04). The findings remained consistent after sub-group analysis in patients without known coronary disease.
Conclusion
The use of scanning line source AC did not meaningfully influence the rate of abnormal MPI results or downstream invasive testing in this cohort. The clinical utility of scanning line source AC may be limited to facilitating stress-first imaging protocols.



J Nucl Cardiol: 05 Apr 2021; epub ahead of print
Singhvi A, Suacier S, Verma I, Felpel K, ... McMahon S, Duvall WL
J Nucl Cardiol: 05 Apr 2021; epub ahead of print | PMID: 33825139
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Abstract

Coronary artery disease in patients with human immunodeficiency virus infection.

Mondal P, Aljizeeri A, Small G, Malhotra S, ... Al-Mallah MH, Jain D
The life expectancy of people infected with human immunodeficiency virus (HIV) is rising due to better access to combination anti-retroviral therapy (ART). Although ART has reduced acquired immune deficiency syndrome (AIDS) related mortality and morbidity, there has been an increase in non-AIDS defining illnesses such as diabetes mellitus, hypercholesterolemia and coronary artery disease (CAD). HIV is a disease marked by inflammation which has been associated with specific biological vascular processes increasing the risk of premature atherosclerosis. The combination of pre-existing risk factors, atherosclerosis, ART, opportunistic infections and coagulopathy contributes to rising CAD incidence. The prevalence of CAD has emerged as a major contributor of morbidity in these patients due to longer life expectancy. However, ART has been associated with lipodystrophy, dyslipidemia, insulin resistance, diabetes mellitus and CAD. These adverse effects, along with drug-drug interactions when ART is combined with cardiovascular drugs, result in significant challenges in the care of this group of patients. Exercise tolerance testing, echocardiography, myocardial perfusion imaging, coronary computed tomography angiography and magnetic resonance imaging help in the diagnosis of CAD and heart failure and help predict cardiovascular outcomes in a manner similar to non-infected individuals. This review will highlight the pathogenesis and factors that link HIV to CAD, presentation and treatment of HIV-patients presenting with CAD and review briefly the cardiac imaging modalities used to identify this entity and help prognosticate future outcomes.



J Nucl Cardiol: 30 Mar 2021; 28:510-530
Mondal P, Aljizeeri A, Small G, Malhotra S, ... Al-Mallah MH, Jain D
J Nucl Cardiol: 30 Mar 2021; 28:510-530 | PMID: 32820424
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Abstract

The \"fixed\" SPECT MPI defect: Where are we and where should we be going?

Gewirtz H
This brief review focuses on reasons why myocardial perfusion imaging (MPI) SPECT defects may appear \"fixed\" (rest vs stress). A combination of technical and physiology factors are responsible in most cases and are discussed. Perhaps the major reason defects will appear fixed is that there is no absolute quantitative measurement of myocardial blood flow (MBF, rest and stress) with which to assess the magnitude and potential direction of change in the defect vs reference zone with stress. Cardiac PET MPI provides absolute measurements of MBF required to understand the clinical significance of the SPECT \"fixed\" defect and are highlighted. Emphasis is given to use of the actual MBF measurements though indexing stress MBF to that of truly normal subjects (RFR or FFRPET) will prove useful in recognition of multi-vessel CAD. The availability of 18F flurpiridaz for clinical use is likely to encourage more widespread adoption of cardiac PET MPI for evaluation of patients with known or suspected CAD.



J Nucl Cardiol: 30 Mar 2021; 28:730-734
Gewirtz H
J Nucl Cardiol: 30 Mar 2021; 28:730-734 | PMID: 33175302
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Abstract

Detecting native and bioprosthetic aortic valve disease using F-sodium fluoride: Clinical implications.

Fletcher AJ, Dweck MR
Calcific aortic valve disease is the most common valvular disease and confers significant morbidity and mortality. There are currently no medical therapies that successfully halt or reverse the disease progression, making surgical replacement the only treatment currently available. The majority of patients will receive a bioprosthetic valve, which themselves are prone to degeneration and may also need replaced, adding to the already substantial healthcare burden of aortic stenosis. Echocardiography and computed tomography can identify late-stage manifestations of the disease process affecting native and bioprosthetic aortic valves but cannot detect or quantify early molecular changes. 18F-fluoride positron emission tomography, on the other hand, can non-invasively and sensitively assess disease activity in the valves. The current review outlines the pivotal role this novel molecular imaging technique has played in improving our understanding of native and bioprosthetic aortic valve disease, as well as providing insights into its feasibility as an important future research and clinical tool.



J Nucl Cardiol: 30 Mar 2021; 28:481-491
Fletcher AJ, Dweck MR
J Nucl Cardiol: 30 Mar 2021; 28:481-491 | PMID: 33175301
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Abstract

Age- and sex-dependent changes of resting amygdalar activity in individuals free of clinical cardiovascular disease.

Haider A, Bengs S, Diggelmann F, Epprecht G, ... Gebhard C, Fiechter M
Purpose
Amygdalar metabolic activity was shown to independently predict cardiovascular outcomes. However, little is known about age- and sex-dependent variability in neuronal stress responses among individuals free of cardiac disease. This study sought to assess age- and sex-specific differences of resting amygdalar metabolic activity in the absence of clinical cardiovascular disease.
Methods
Amygdalar metabolic activity was assessed in 563 patients who underwent multimodality imaging by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography and echocardiography for the evaluation of cardiac function.
Results
After exclusion of 294 patients with structural or functional cardiovascular pathologies, 269 patients (128 women) remained in the final population. 18F-FDG amygdalar activity significantly decreased with age in men (r = - 0.278, P = 0.001), but not in women (r = 0.002, P = 0.983). Similarly, dichotomous analysis confirmed a lower amygdalar activity in men ≥ 50 years as compared to those < 50 years of age (0.79 ± 0.1 vs. 0.84 ± 0.1, P = 0.007), which was not observed in women (0.81 ± 0.1 vs. 0.82 ± 0.1, P = 0.549). Accordingly, a fully adjusted linear regression analysis identified age as an independent predictor of amygdalar activity only in men (B-coefficient - 0.278, P = 0.001).
Conclusion
Amygdalar activity decreases with age in men, but not in women. The use of amygdalar activity for cardiovascular risk stratification merits consideration of inherent age- and sex-dependent variability.



J Nucl Cardiol: 30 Mar 2021; 28:427-432
Haider A, Bengs S, Diggelmann F, Epprecht G, ... Gebhard C, Fiechter M
J Nucl Cardiol: 30 Mar 2021; 28:427-432 | PMID: 33442821
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