Vascular/perivascular inflammation in IgG4-related disease.

Imai S, Tahara N, Igata S, Tahara A, ... Fukumoto Y, Tayama E
Background
Immunoglobulin G4-related disease (IgG4-RD) is characterized by the infiltration of IgG4-positive plasma cells and fibrosclerotic inflammation in multiple organs. Although vascular complications are present in some patients with IgG4-RD, vascular and/or perivascular inflammatory activity compared to control subjects remains unknown. This study sought to investigate vascular/perivascular inflammation in IgG4-RD patients compared to control subjects using 18F-fluorodeoxyglucose-positron emission tomography combined with computed tomography (FDG-PET/CT).
Methods
We examined 37 consecutive patients diagnosed as IgG4-RD (29 males, mean age of 64.3 ± 8.3 years old), who underwent FDG-PET/CT. Thirty-seven age- and gender-matched subjects without IgG4-RD were employed as controls. Vascular/perivascular inflammation was quantified by blood-normalized standardized uptake value, known as a target-to-background ratio (TBR).
Results
All IgG4-RD patients presented with multiple region involvements. Twelve (32.4%) of the IgG4-RD patients had vascular complications, all of which appeared in the abdominal aorta. IgG4-RD patients had significantly higher TBR values in the descending aorta, abdominal aorta, and common iliac artery than control subjects. Also, IgG4-RD patients with vascular complication exhibited higher TBR values in the infra-renal aorta and common iliac artery than those without vascular complication.
Conclusions
We found that vascular FDG activity is significantly elevated in IgG4-RD patients regardless of vascular complication than control subjects. FDG-PET/CT is a useful modality for assessing vascular/perivascular inflammation, which may contribute vascular complication in IgG4-RD patients.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 25 Oct 2021; epub ahead of print

Effect of left ventricular mechanical dyssynchrony assessed pre-renal transplantation on cardiovascular death post transplantation.

Morgan WS, Ives CW, Farag AA, Kumar V, ... Iskandrian AE, Hage FG
Background
SPECT myocardial perfusion imaging (MPI) provides an assessment of LV mechanical dyssynchrony (LVMD) which correlates with CVD outcomes in diverse populations including those awaiting renal transplant (RT). The current study examines the association of LVMD on pre-transplant MPI with long-term CVD mortality post RT.
Methods
We identified consecutive patients who underwent RT at the University of Alabama at Birmingham between 2008 and 2012 from our prospectively collected database. 675 patients in the database underwent MPI and had images amenable for phase analysis. A blinded investigator retrieved the studies and derived LVMD indices including histogram bandwidth (BW), standard deviation (SD), phase peak, phase skewness, and phase kurtosis. The primary outcome was CVD death after RT.
Results
The study cohort had a median age of 54 years, 56% were men, 43% had diabetes, and 7% had prior myocardial infarction. Patients were on dialysis for a median of 3.4 years prior to RT and 34% received living donor transplants. During a median follow-up time after RT of 4.7 years (IQR 3.5 to 6.3 years) 59 patients (9%) succumbed to CVD death. Patients with wider BW, wider SD, lower skewness, and lower kurtosis had an increased risk of CVD death. On multivariate adjustment, BW and skewness remained as independent predictors of CVD deaths.
Conclusions
LVMD by phase analysis of gated SPECT MPI is associated with increased risk of CVD death after RT. This association is independent of demographics, comorbidities, and traditional findings on MPI and added incremental prognostic information. Assessment of LVMD should be considered for risk stratification in these patients.

© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

J Nucl Cardiol: 21 Oct 2021; epub ahead of print

Post-reconstruction attenuation correction for SPECT myocardium perfusion imaging facilitated by deep learning-based attenuation map generation.

Liu H, Wu J, Shi L, Liu Y, ... Liu YH, Liu C
Background
Attenuation correction can improve the quantitative accuracy of single-photon emission computed tomography (SPECT) images. Existing SPECT-only systems normally can only provide non-attenuation corrected (NC) images which are susceptible to attenuation artifacts. In this work, we developed a post-reconstruction attenuation correction (PRAC) approach facilitated by a deep learning-based attenuation map for myocardial perfusion SPECT imaging.
Methods
In the PRAC method, new projection data were estimated via forwardly projecting the scanner-generated NC image. Then an attenuation map, generated from NC image using a pretrained deep learning (DL) convolutional neural network, was incorporated into an offline reconstruction algorithm to obtain the attenuation-corrected images from the forwardly projected projections. We evaluated the PRAC method using 30 subjects with a DL network trained with 40 subjects, using the vendor-generated AC images and CT-based attenuation maps as the ground truth.
Results
The PRAC methods using DL-generated and CT-based attenuation maps were both highly consistent with the scanner-generated AC image. The globally normalized mean absolute errors were 1.1% ± .6% and .7% ± .4% and the localized absolute percentage errors were 8.9% ± 13.4% and 7.8% ± 11.4% in the left ventricular (LV) blood pool, respectively, and - 1.3% ± 8.0% and - 3.8% ± 4.5% in the LV myocardium for PRAC methods using DL-generated and CT-based attenuation maps, respectively. The summed stress scores after PRAC using both attenuation maps were more consistent with the ground truth than those of the NC images.
Conclusion
We developed a PRAC approach facilitated by deep learning-based attenuation maps for SPECT myocardial perfusion imaging. It may be feasible for this approach to provide AC images for SPECT-only scanner data.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 19 Oct 2021; epub ahead of print

Hybrid imaging of neuroendocrine tumors in the heart: Union is strength.

Marketou ME, Kapsoritakis N, Bourogianni O, Patrianakos A, ... Parthenakis F, Koukouraki S
Cardiac neuroendocrine tumors (NETs) are particularly rare tumors that can lead to a very poor clinical outcome, partly because of metastases but mainly because of manifestations of the hormonal activity they exhibit. Prompt diagnosis is important in order to start the most effective treatment for their removal or management, with the fewest complications. They are often difficult to diagnose, especially in their early stages. One of the reasons for this is that the heart is an organ with a high rate of metabolism and is located in close proximity to other high-metabolism organs. In addition, the anatomic location and their small size render their diagnosis extremely challenging. In recent years, hybrid imaging methods have revolutionized the diagnostic approach to oncology patients and have established a place in the diagnosis of cardiac NETs, because they provide both anatomical and functional information at the same time. Positron emission tomography/computed tomography (PET/CT), PET/magnetic resonance imaging (PET/MRI) and single-photon emission computed tomography/CT (SPECT/CT) are widely used in clinical practice because of the very important metabolic information, the high sensitivity and specificity. However, prospective studies are needed to confirm the true clinical and prognostic value of various hybrid imaging diagnostic techniques in cardiac NETs.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 06 Oct 2021; epub ahead of print

Amiodarone attenuates cardiac Rubidium-82 in consecutive PET/CT scans in a rodent model.

Bentsen S, Bang LE, Hasbak P, Kjaer A, Ripa RS
Background
Risk stratification and diagnosis using Rubidium-82 (⁸²Rb) positron emission tomography (PET) is a routine clinical approach in coronary artery disease (CAD). Various drugs are used to treat CAD; however, whether any of them change the uptake of ⁸²Rb in the heart has not been investigated. The aim of this study is to determine whether drugs used in treatment of CAD affect the uptake of ⁸²Rb in the heart in healthy rats.
Methods
Seventy-seven Sprague-Dawley rats were included in the cross-sectional study. All rats underwent baseline ⁸²Rb PET/CT and divided into eleven groups treated with different drugs. One group was control group (no treatment), eight groups were treated with monotherapy (amiodarone, acetylsalicylic acid (ASA), clopidogrel, ticagrelor, atorvastatin, enalapril, amlodipine, metoprolol succinate), and two groups were treated with polypharmacy (ASA, ticagrelor, atorvastatin, amlodipine or ASA, clopidogrel, atorvastatin, amlodipine). Once a day, they were administered pharmacological therapy through oral gavage, and on day seven, follow-up scanned with ⁸²Rb PET/CT.
Results
In the control group without pharmacological treatment, no difference in the standard uptake value (SUV) ratio between heart and muscle from baseline to follow-up (5.8 vs 7.0, P = .3) was found. The group treated with amiodarone had a significantly reduced SUV ratio from baseline to follow-up (5.8 vs 5.1, P = .008). All other drugs investigated had no difference in SUV ratio from baseline to follow-up.
Conclusion
In this study, we showed that drugs normally used to treat CAD do not affect the uptake of ⁸²Rb. However, amiodarone result in a significantly lowered ⁸²Rb uptake, compared to control. This information about amiodarone would probably not change the size assessment of a myocardial perfusion defect in a clinical setting. However, it could change the kinetic parameters when assessing absolute myocardial blood flow in patients treated with amiodarone.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 04 Oct 2021; epub ahead of print

The prevalence and predictors of inducible myocardial ischemia among patients referred for radionuclide stress testing.

Rozanski A, Miller RJH, Han D, Gransar H, ... Thomson LB, Berman DS
Background
The frequency of inducible myocardial ischemia has declined in contemporary stress test cohorts, suggesting a need to re-evaluate its optimal use. To-date, however, a comprehensive analysis of the most potent predictors of myocardial ischemia among cardiac stress test patients has not been conducted.
Methods
We assessed 27,615 patients referred for stress-rest SPECT myocardial perfusion imaging between January 1, 2004 and December 31, 2017. Chi-square analysis was used to ascertain the most potent predictors of ischemia.
Results
Among our cohort, CAD status (presence/absence of known CAD), rest left ventricular ejection fraction (LVEF), and typical angina were the most potent predictors of ischemia. The frequency of ischemia was only 6.6% among patients with an LVEF > 55% but 38.1% for patients with LVEF < 45% (P < 0.001). The frequency of myocardial ischemia was fourfold higher among patients with known CAD vs no known CAD (28.0% vs 6.5%, P < 0.001) and approximately threefold higher among patients with typical angina vs patients with atypical symptoms (P < 0.001).
Conclusions
The frequency of myocardial ischemia varies markedly according to the common clinical parameters and is particularly high among patients with known CAD, low LVEF, and typical angina. These observations may be used to develop more cost-effective strategies for referring patients for cardiac stress testing.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 03 Oct 2021; epub ahead of print

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

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

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 02 Oct 2021; epub ahead of print

Serial changes in cardiac sympathetic nervous function after transcatheter aortic valve replacement: A prospective observational study using I-meta-iodobenzylguanidine imaging.

Kadoya Y, Zen K, Tamaki N, Nakamura S, ... Yaku H, Matoba S
Background
Transcatheter aortic valve replacement (TAVR) can rapidly improve cardiac sympathetic nervous function (CSNF) within 2 weeks in patients with aortic stenosis (AS). However, whether such short-term improvements will be sustained thereafter remains unclear.
Methods
Patients with severe AS who underwent TAVR between October 2017 and June 2019 were enrolled in this single-center, prospective, observational study. ¹²³I-meta-iodobenzylguanidine imaging was performed at baseline, within 2 weeks after TAVR, and at 6 to 12 months post-TAVR to evaluate the heart-mediastinum ratio (H/M) and washout rate.
Results
Of 183 consecutive patients, 75 (19 men; median age: 86 years) were evaluated. The late H/M significantly improved within 2 weeks after TAVR (P = .041) and further improved over 6 to 12 months after TAVR (P = .041). Multivariate analysis revealed that the baseline mean aortic valve pressure gradient (mPG) was an independent predictor of mid-term improvement in the late H/M (> 0.1) (P = .037). Patients with a high baseline mPG (≥ 58 mmHg) exhibited a significantly greater increase in the late H/M than those with a low baseline mPG (< 42 mmHg) (0.24 vs 0.01; P = .029).
Conclusion
CSNF demonstrated sustained improvement from within 2 weeks after TAVR until 6 to 12 months later. Such improvement was related to baseline hemodynamic AS severity.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 23 Sep 2021; epub ahead of print

ASNC Imaging Indications (ASNC-I): Multisocietal indications for radionuclide imaging in the multimodality context-Series rationale and methodology.

Bourque JM, Einstein AJ, Dorbala S
Background
Appropriate use criteria (AUC) enhance application of cardiovascular imaging techniques but have been applied in limited settings, primarily in common cardiovascular disease processes. There are several complex systemic diseases with cardiovascular implications and special populations with unique cardiovascular considerations that could benefit from appropriateness analysis. Moreover, the high medical complexity of these topics indicate they would benefit from high-yield expert consensus recommendations of the available imaging options. The ASNC Imaging Indications (ASNC-I²) Series will provide a concise overview of relevant disease processes and their multimodality evaluation and will provide consensus clinical indications, diagnostic criteria, and clinical algorithms with representative clinical cases.
Methods
For each ASNC-I² document, a diverse writing group and rating panel will be composed of experts from societies pertinent to the topic, including relevant imaging societies and clinical societies that manage the disease under evaluation. The rating panel will follow robust modified Delphi methodology and commonly-accepted appropriateness methods to create consensus diagnostic criteria, clinical algorithms, and clinical indications that they will then rate with level of agreement recorded. The clinical and imaging experts will provide concise, high-yield clinical summaries of the disease process, the non-imaging evaluation, and multimodality imaging. Relevant cases will be provided highlighting application of the diagnostic criteria and clinical algorithms.
Conclusion
The ASNC Imaging Indications (ASNC-I²) Series will complement the diverse portfolio of documents from ASNC. It will use a multisocietal approach with robust appropriateness methodology to guide use of radionuclide imaging in the multimodality imaging context for the cardiovascular care of patients.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 23 Sep 2021; epub ahead of print

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

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

[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 (SUV_max) of ten arteries by SUV_mean 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

\"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

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

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

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

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

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

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

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. SUV_max, SUV_peak, and SUV_mean were compared between Q_INT and Q_EXT SPECT datasets. Global SUV_max and SUV_peak 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. SUV_max, SUV_peak, and SUV_mean showed an excellent correlation between Q_INT and Q_EXT SPECT datasets, though mean SUV_mean differed significantly between the two groups. Global SUV_max and SUV_peak 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

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

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.

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 30 Jul 2021; 28:1545-1552

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

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