Role of F-FDG PET/CT imaging in cardiac and pericardial masses.

Yin H, Mao W, Tan H, Zhu N, ... Yu H, Shi H
Background
Considering the few reported cardiac masses, PET/CT in the imaging workup of cardiac masses is not well established. This retrospective study analyzed the role of F-FDG PET/CT imaging in cardiac/pericardial masses.
Methods and results
Fifty-nine patients with newly diagnosed cardiac/pericardial masses who underwent PET/CT and transthoracic echocardiography (TTE) were recruited. Echocardiographic and PET/CT characteristics were evaluated for predictive value in differentiating malignant and non-malignant lesions using histologic confirmation as the gold standard. The McNemar test was used to test the differences in sensitivity between PET/CT and TTE. F-FDG PET/CT had higher sensitivity in determining the malignancy of cardiac/pericardial masses compared to TTE (sensitivity, 96.6% vs 72.4%, P = .039). However, when pericardial masses were excluded from the analysis, the difference in sensitivity between the two was not statistically significant (sensitivity, 95.6% vs 78.3%, P = .219). F-FDG PET/CT identified two malignant pericardial masses missed on TTE, changed the diagnostic orientation of TTE in 15 patients, and found seven patients with extracardiac lesions in 29 malignant patients.
Conclusions
PET/CT was an effective additional image modality in patients with suspected malignant cardiac mass for further confirmation and to screen for potential metastasis.



J Nucl Cardiol: 17 Jan 2021; epub ahead of print

Evaluation of non-stenotic carotid atherosclerotic plaques with combined FDG-PET imaging and CT angiography in patients with ischemic stroke of unknown origin.

Mikail N, Meseguer E, Lavallée P, Klein I, ... Amarenco P, Hyafil F
Objectives
Non-stenotic plaques are an underestimated cause of ischemic stroke. Imaging aspects of high-risk carotid plaques can be identified on CT angiography (CTA) and 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET) imaging. We evaluated in patients with cryptogenic ischemic stroke the usefulness of FDG-PET-CTA.
Methods
44 patients imaged with CTA and FDG-PET were identified retrospectively. Morphological features were identified on CTA. Intensity of FDG uptake in carotid arteries was quantified on PET.
Results
Patients were imaged 7 ± 8 days after stroke. 44 non-stenotic plaques with increased 18F-FDG uptake were identified in the carotid artery ipsilateral to stroke and 7 contralateral. Most-diseased-segment TBR on FDG-PET was higher in artery ipsilateral vs. contralateral to stroke (2.24 ± 0.80 vs. 1.84 ± 0.50; p < .05). In the carotid region with high FDG uptake, prevalence of hypodense plaques and extent of hypodensity on CTA were higher in artery ipsilateral vs. contralateral to stroke (41% vs. 11%; 0.72 ± 1.2 mm vs. 0.13 ± 0.43 mm; p < .05).
Conclusions
In patients with ischemic stroke of unknown origin and non-stenotic plaques, we found an increased prevalence of high-risk plaques features ipsilateral vs. contralateral to stroke on FDG-PET-CTA imaging suggesting a causal role for these plaques.



J Nucl Cardiol: 17 Jan 2021; epub ahead of print

Health economics-based verification of functional myocardial ischemia evaluation of stable coronary artery disease in Japan: A long-term longitudinal study using propensity score matching.

Takura T, Yokoi H, Tanaka N, Matsumoto N, ... Nakata T, J-CONCIOUS Investigators
Background
The procedural numbers and medical costs of percutaneous coronary intervention (PCI), mainly elective PCI, have been increasing in Japan. Owing to increased interest in the appropriateness of coronary revascularization, we conducted this medical economics-based evaluation of testing and diagnosis of stable coronary artery disease (CAD).
Methods and results
We reviewed patients\' medical insurance data to identify stable CAD patients who underwent coronary computed tomography angiography, cardiac single-photon emission computed tomography, coronary angiography, or fractional flow reserve. Subjects were divided into anatomical and functional evaluation groups according to the modality of testing, and background factors were matched by propensity score. The endpoints were major adverse cardiovascular events (MACE), life years (LYs), medical costs, and cost-effectiveness analysis (CEA). The observations were performed for 36 months. MACE, medical costs, and CEA of the functional group in the overall category were trending to be better than the anatomical group (MACE, P = .051; medical costs: 3,105 US$ vs 4,430 US$, P = .007; CEA: 2,431 US$/LY vs 2,902 US$/LY, P = .043).
Conclusions
The functional evaluation approach improved long-term clinical outcomes and reduced cumulative medical costs. As a result, the modality composition of functional myocardial ischemia evaluation was demonstrated to offer superior cost-effectiveness in stable CAD.



J Nucl Cardiol: 17 Jan 2021; epub ahead of print

Tracking the progress of inflammation with PET/MRI in a canine model of myocardial infarction.

Wilk B, Smailovic H, Wisenberg G, Sykes J, ... Thiessen JD, Prato FS
Background
Following myocardial infarction, tissue undergoes pathophysiological changes involving inflammation and scar tissue formation. However, little is known about the pathophysiology and prognostic significance of any corresponding changes in remote myocardium. The aim of this study was to investigate the potential application of a combined constant infusion of F-FDG and Gd-DTPA to quantitate inflammation and extracellular volume (ECV) from 3 to 40 days after myocardial infarction.
Methods
Eight canine subjects were imaged at multiple time points following induction of an MI with a 60-minute concurrent constant infusion of Gd-DTPA and F-FDG using a hybrid PET/MRI scanner.
Results
There was a significant increase in ECV in remote myocardium on day 14 post-MI (P = .034) and day 21 (P = .021) compared to the baseline. ECV was significantly elevated in the infarcted myocardium compared to remote myocardium at all time points post-MI (days 3, 7, 14, 21, and 40) (P < .001) while glucose uptake was also increased within the infarct on days 3, 7, 14, and 21 but not 40.
Conclusions
The significant increase in ECV in remote tissue may be due to an ongoing inflammatory process in the early weeks post-infarct.



J Nucl Cardiol: 17 Jan 2021; epub ahead of print

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 F-fluorodeoxyglucose (F-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. F-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: 12 Jan 2021; epub ahead of print

The prognostic value of I-mIBG SPECT cardiac imaging in heart failure patients: a systematic review.

Pontico M, Brunotti G, Conte M, Corica F, ... Farcomeni A, De Vincentis G

This systematic review aimed to evaluate the prognostic value of Iodine123 Metaiodobenzylguanidine (I-mIBG) SPECT myocardial imaging in patients with heart failure (HF) and to assess whether semi-quantitative SPECT scores can be useful for accurate risk stratification concerning arrhythmic event (AE) and sudden cardiac death (SCD) in this cohort. A systematic literature search of studies published until November 2020 regarding the application of I-mIBG SPECT in HF patients was performed, in Pubmed, Scopus, Medline, Central (Cochrane Library) and Web Of Science databases, including the words \"MIBG\", \"metaiodobenzylguanidine\", \"heart\", \"spect\", and \"tomographic\". The included studies had to correlate I-mIBG SPECT scores with endpoints such as overall survival and prevention of AE and SCD in HF patients. According to the sixteen studies included, the analysis showed that 123I-mIBG SPECT scores, such as summed defect score (SDS), regional wash-out (rWO), and regional myocardial tracer uptake, could have a reliable prognostic value in patients with HF. An increased SDS or rWO, as well as a reduced I-mIBG myocardial uptake, have proven to be effective in predicting AE- and SCD-specific risk in HF patients. Despite achieved results being promising, a more reproducible standardized method for semi-quantitative analysis and further studies with larger cohort are needed for I-mIBG SPECT myocardial imaging to be as reliable and, thus, accepted as the conventional I-mIBG planar myocardial imaging.



J Nucl Cardiol: 12 Jan 2021; epub ahead of print

Assessment of myocardial sympathetic innervation with 18F-FDOPA-PET/CT in patients with autonomic dysfunction: feasibility study in IPD patients.

Goyal H, Sharma A, Patel C, Deepak KK, ... Bal CS, Goyal V
Background
Dysfunction and denervation of myocardial nor-adrenergic sympathetic neurons has been documented in IPD patients with dysautonomia. The aim of this study was to evaluate the feasibility of single tracer imaging of myocardial sympathetic and cerebral striatal involvement in these patients.
Methods
Twenty-two controls (mean-age 59.09 ± 12.39 years, 15 men) with no clinical autonomic-dysfunction and normal striatal-uptake in 18F-FDOPA-PET/CT; and 28 patients (mean-age 58.18 ± 8.25 years, 18 men) with autonomic-dysfunction (in Autonomic Function Tests) and striatal dopaminergic-dysfunction were enrolled. Both cardiac-PET/CT (40 minutes post IV-injection of 185-259MBq 18F-FDOPA) and Brain-PET/CT (60 minutes post-IV) were acquired in same session. ROIs were drawn over the entire left ventricular myocardium, individual walls and mediastinum for quantification. Patients and controls were followed-up for 26.93 ± 5.43 months and 37.91 ± 8.63 months, respectively.
Results
Striatal and myocardial-parameters were significantly lower in patients compared to controls; with Myocardium/mediastinal ratio (MwMR) yielding the area-under-the-curve of .941 (P < .001). MwMR correlated negatively with the drop in systolic blood pressure (SBP) during AFTs {Pearson-coefficient (-).565, P = .002}. Mean MwMR in patients with abnormal-AFTs was significantly lower than patients with borderline-AFTs (1.39 ± .12 vs 1.55 ± .10; P = .002). 9/20 patients with abnormal-AFTs showed functional worsening during follow-up, compared to 2/8 with borderline-AFTs.
Conclusion
Single tracer, single session imaging of striatal and cardiac sympathetic dysfunction in patients with advanced IPD is feasible with use of 18F-FDOPA. Significantly reduced 18F-FDOPA uptake is seen in the myocardium of the IPD patients with sympathetic dysfunction.



J Nucl Cardiol: 09 Jan 2021; epub ahead of print

Divergence of acetate uptake in proinflammatory and inflammation-resolving macrophages: implications for imaging atherosclerosis.

Demirdelen S, Mannes PZ, Aral AM, Haddad J, ... Gomez D, Tavakoli S
Background
Metabolic divergence of macrophages polarized into different phenotypes represents a mechanistically relevant target for non-invasive characterization of atherosclerotic plaques using positron emission tomography (PET). Carbon-11 (C)-labeled acetate is a clinically available tracer which accumulates in atherosclerotic plaques, but its biological and clinical correlates in atherosclerosis are undefined.
Methods and results
Histological correlates of C-acetate uptake were determined in brachiocephalic arteries of western diet-fed apoE mice. The effect of polarizing stimuli on C-acetate uptake was determined by proinflammatory (interferon-γ + lipopolysaccharide) vs inflammation-resolving (interleukin-4) stimulation of murine macrophages and human carotid endarterectomy specimens over 2 days. C-acetate accumulated in atherosclerotic regions of arteries. CD68-positive monocytes/macrophages vs smooth muscle actin-positive smooth muscle cells were the dominant cells in regions with high vs low C-acetate uptake. C-acetate uptake progressively decreased in proinflammatory macrophages to 25.9 ± 4.5% of baseline (P < .001). A delayed increase in C-acetate uptake was induced in inflammation-resolving macrophages, reaching to 164.1 ± 21.4% (P < .01) of baseline. Consistently, stimulation of endarterectomy specimens with interferon-γ + lipopolysaccharide decreased C-acetate uptake to 66.5 ± 14.5%, while interleukin-4 increased C-acetate uptake to 151.5 ± 25.8% compared to non-stimulated plaques (P < .05).
Conclusions
Acetate uptake by macrophages diverges upon proinflammatory and inflammation-resolving stimulation, which may be exploited for immunometabolic characterization of atherosclerosis.



J Nucl Cardiol: 07 Jan 2021; epub ahead of print

Cardiopulmonary transit time: A novel PET imaging biomarker of in vivo physiology for risk stratification of heart transplant recipients.

Harms HJ, Bravo PE, Bajaj NS, Zhou W, ... Givertz MM, Di Carli MF
Background
Myocardial blood flow (MBF) can be quantified using dynamic PET studies. These studies also inherently contain tomographic images of early bolus displacement, which can provide cardiopulmonary transit times (CPTT) as measure of cardiopulmonary physiology. The aim of this study was to assess the incremental prognostic value of CPTT in heart transplant (OHT) recipients.
Methods
94 patients (age 56 ± 16 years, 78% male) undergoing dynamic N-ammonia stress/rest studies were included, of which 68 underwent right-heart catherization. A recently validated cardiac allograft vasculopathy (CAV) score based on PET measures of regional perfusion, peak MBF and left-ventricular (LV) ejection fraction (LVEF) was used to identify patients with no, mild or moderate-severe CAV. Time-activity curves of the LV and right ventricular (RV) cavities were obtained and used to calculate the difference between the LV and RV bolus midpoint times, which represents the CPTT and is expressed in heartbeats. Patients were followed for a median of 2.5 years for the occurrence of major adverse cardiac events (MACE), including cardiovascular death, hospitalization for heart failure or acute coronary syndrome, or re-transplantation.
Results
CPTT was significantly correlated with cardiac filling pressures (r = .434, P = .0002 and r = .439, P = .0002 for right atrial and pulmonary wedge pressure), cardiac output (r = - .315, P = .01) and LVEF (r = - .513, P < .0001). CPTT was prolonged in patients with MACE (19.4 ± 6.0 vs 14.5 ± 3.0 heartbeats, P < .001, N = 15) with CPTT ≥ 17.75 beats showing optimal discriminatory value in ROC analysis. CPTT ≥ 17.75 heartbeats was associated with a 10.1-fold increased risk (P < .001) of MACE and a 7.3-fold increased risk (P < .001) after adjusting for PET-CAV, age, sex and time since transplant.
Conclusion
Measurements of cardiopulmonary transit time provide incremental risk stratification in OHT recipients and enhance the value of multiparametric dynamic PET imaging, particularly in identifying high-risk patients.



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

Comparison of left ventricle mechanical dyssynchrony parameters in ischemic and non-ischemic patients using N-NH PET/CT.

Mazzoletti A, Albano D, Bertagna F, Mesquita CT, Giubbini R
Background-aim
The relationship between perfusion pattern and stress-induced changes in Left Ventricular Mechanical Dyssynchrony (LVMD) has been previously described with controversial results using stress-rest perfusion imaging studies. The aim of this study was to assess the relationship between perfusion pattern and stress-induced changes in LVMD usingo regadenoson/rest13N-NH3 PET/CT.
Methods
There were 74 patients who underwent stress-rest 13N-NH PET/CT from January 2014 to October 2018 excluding patients with left bundle branch block, ventricular pacing and myocardial necrosis. The patients were divided into those with reversible perfusion defects at stress (Ischemic group, n = 18) and patients without reversible perfusion defects (non-ischemic group, n = 56). The LVMD parameters included: phase standard deviation (PSD) and phase histogram bandwidth (PHB), after stress and at rest. The ΔPSD (post-stressPSD-restPSD) and ΔPHB (post-stressPHB-restPHB) were calculated to measure stress-induced changes in LVMD.
Results
There were no significant differences in LVMD parameters between post-stress and at rest in both groups. The PSD post-stress, ΔPSD and PHB post-stress were significantly higher in the ischemic group.
Conclusions
Using a vasodilator as a stress, the PSD and PHB post-stress and ΔPSD were significantly higher in the ischemic patients than the non-ischemic group, while there were no significant differences in each cohort between stress and rest indices.



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

Prognostic value of early left ventricular ejection fraction reserve during regadenoson stress solid-state SPECT-MPI.

Otaki Y, Fish MB, Miller RJH, Lemley M, Slomka PJ
Background
We hypothesized early post-stress left ventricular ejection fraction reserve (EFR) on solid-state-SPECT is associated with major cardiac adverse events (MACE).
Methods
151 patients (70 ± 12 years, male 50%) undergoing same-day rest/regadenoson stress Tc-sestamibi solid-state SPECT were followed for MACE. Rest imaging was performed in the upright and supine positions. Early stress imaging was started 2 minutes after the regadenoson injection in the supine position and followed by late stress acquisition in the upright position. Total perfusion deficit (TPD) and functional parameters were quantified automatically. EFR, ∆end-diastolic volume (EDV), and end-systolic volume (ESV) were calculated as the difference between stress and rest values in the same position. EFR < 0%, ∆EDV ≥ 5 ml, or ∆ESV ≥ 5 ml was defined as abnormal.
Results
During the follow-up (mean 3.2 years), 28 MACE occurred (19%). In Kaplan-Meier analysis, there was a significantly decreased event-free survival in patients with early EFR < 0% (P = 0.004). Similarly, there was a decreased event-free survival in patients with ∆ESV ≥ 5 ml at early stress (P = 0.003). However, EFR, ∆EDV, and ∆ESV at late stress were not associated with MACE-free survival. Cox proportional hazards model adjusting for clinical information and stress TPD demonstrated that EFR, ∆EDV, and ∆ESV at early stress were significantly associated with MACE (P < 0.05 for all).
Conclusions
Reduced early post-stress EFR on vasodilator stress solid-state SPECT is associated with MACE.



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

Assessment of atherosclerosis in multiple myeloma and smoldering myeloma patients using F- sodium fluoride PET/CT.

Arani LS, Zirakchian Zadeh M, Saboury B, Revheim ME, ... Høilund-Carlsen PF, Alavi A
Background
To compare the NaF uptake in the thoracic aorta and whole heart, as an early indicator of atherosclerosis, in multiple myeloma (MM) and smoldering multiple myeloma (SMM) patients with a healthy control (HC) group.
Methods
Forty-four untreated myeloma patients (35 MM and nine SMM) and twenty-six age and gender-matched HC subjects were collected. Each individual\'s NaF uptake in three parts of the aorta (AA: ascending aorta, AR: aortic arch, DA: descending aorta) and the whole heart was segmented. Average global standardized uptake value means were derived by sum of the product of each slice area divided by the sum of those slice areas. Results were reported as target to background ratio (TBR).
Results
There was a significant difference between the NaF uptake in the thoracic aorta of myeloma and HC groups [AA (myeloma = 1.82 ± 0.21, HC = 1.24 ± 0.02), AR (myeloma = 1.71 ± 0.19, HC = 1.28 ± 0.03) and DA (myeloma = 1.96 ± 0.28, HC = 1.38 ± 0.03); P-values < 0.001]. The difference in the whole heart NaF uptake between two groups was also significant (P < 0.001).
Conclusions
We observed a higher uptake of NaF in the thoracic aorta and whole heart of myeloma patients in comparison to the matched control group.



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

Tc-99m HMDP bone scintigraphy for cardiac amyloidosis diagnosis: A false positive case.

Lades G, Carpenet H, Benoit U, Aboyans V, Monteil J

A 68-year-old man with heart failure (left ventricular ejection fraction = 30%) and normal coronary angiography underwent bone scintigraphy for suspected transthyretin-related cardiac amyloidosis (CA).1 He received 532 MBq (14.3 mCi) Tc-99m hydroxy-methyl-diphosphonate (HMDP) and data were acquired 2 hours after injection. On anterior and posterior whole-body scans (Figure 1 A and B), diffuse cardiac, hepatic, and soft-tissue uptake of the radiotracer was seen, in association with low skeletal uptake. It was established that the patient had recently been hospitalized for heart failure exacerbation and had received an intravenous iron injection, which is a recommended treatment for heart failure.2 In consultation with our hospital\'s cardiology team, it was decided to repeat the bone scan at a time when the patient had received no recent iron infusion. Two months after the first bone scan, the patient received 556 MBq (15 mCi) of 99m-Tc HMDP, and no cardiac, hepatic, or soft-tissue uptake was detected (Figure 1C and D).



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

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 Rb or NH (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 (MFR) were then calculated using an inverse power function. For NH, there was good correlation between MFR and MFR values (R = 0.63), with similar results for Rb (R = 0.73). There was no bias in the MFR values with either tracer. The overall diagnostic performance of MFR for detection of MFR < 2 was good with ROC area under the curve (AUC) = 83.2 ± 1.2% for NH and AUC = 90.4 ± 0.7% for Rb.
Conclusion
MFR was estimated with good accuracy using Rb and NH 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: 02 Jan 2021; epub ahead of print

Evaluation of cardiac allograft vasculopathy by positron emission tomography.

Feher A, Sinusas AJ

Cardiac allograft vasculopathy (CAV) remains one of the most important late occurring complications in heart transplant (HT) recipients significantly effecting graft survival. Recently, there has been tremendous focus on the development of effective and safe non-invasive diagnostic strategies for the diagnosis of CAV employing a wide range of imaging technologies. During the past decade multiple studies have been published using positron emission tomography (PET) myocardial perfusion imaging, establishing the value of PET myocardial blood flow quantification for the evaluation of CAV. These independent investigations demonstrate that PET can be successfully used to establish the diagnosis of CAV, can be utilized for prognostication and may be used for serial monitoring of HT recipients. In addition, molecular imaging techniques have started to emerge as new tools to enhance our knowledge to better understand the pathophysiology of CAV.



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

Prognostic value of myocardial perfusion imaging in patients with chronic kidney disease: A systematic review and meta-analysis.

Cantoni V, Green R, Acampa W, Assante R, ... Petretta M, Cuocolo A
Background
We performed a systematic review and meta-analysis to investigate the prognostic value of stress myocardial perfusion single-photon emission computed tomography (MPS) in predicting adverse cardiovascular events in patients with chronic kidney disease (CKD).
Methods
Studies published from inception until July 2020 were identified by PubMed and Embase databases search. Studies were included if they evaluated CKD patients referred for stress MPS, providing data on adjusted hazard ratio (HR) for the occurrence of adverse events. For studies providing only non-adjusted HR, the univariable risk estimate was included in the analysis. Pooled HR and 95% confidence interval (CI) were estimated using a random effects model to compare patients with abnormal and normal MPS. Whenever possible, incidence rate ratio (IRR) was also calculated and pooled.
Results
Sixteen eligible studies were identified including 7834 patients with a follow-up range from 1 to 4.4 years. Eleven articles included patients with end-stage renal disease (IV-V CKD stage), 3 articles with III-V CKD stage and 2 articles with I-V CKD stage. The pooled HR for the occurrence of adverse events was 2.02 (95% CI 1.68-2.42) and heterogeneity was 34%. Among the included studies, 5 reported the HR for the occurrence of hard events, with a pooled HR of 2.36 (95% CI 1.77-3.13). A total of 8 studies reported data useful to calculate the IRR in patients with normal and abnormal perfusion. The pooled IRR was 2.37 (95% CI 1.63-3.47) and heterogeneity was 60%. At meta-regression analysis, we found an association between HR for adverse events and age, hypertension and smoking, while no significant association was found between HR for hard events and demographic and clinical variables.
Conclusions
In patients with CKD an abnormal myocardial perfusion at stress MPS is associated with adverse cardiovascular events.



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

Abnormal vasodilator stress electrocardiogram with normal myocardial perfusion: Clinical decision-making and review of literature.

Kassab K, Al-Ogaili A, Malhotra S

Ischemic electrocardiographic (ECG) changes during vasodilator stress testing in the presence of abnormal myocardial perfusion imaging (MPI) are associated with more severe coronary artery disease (CAD). However, significance of ECG changes during vasodilator stress test with normal MPI has been controversial. Here, we discuss two cases of significant ischemic ECG changes with vasodilator stress and normal MPI, whose subsequent workup revealed severe obstructive CAD. We also review the available literature on the occurrence and mechanism of these discrepant findings and propose recommendations for management.



J Nucl Cardiol: 31 Dec 2020; epub ahead of print

Splenic switch-off as a novel marker for adenosine response in nitrogen-13 ammonia PET myocardial perfusion imaging: Cross-validation against CMR using a hybrid PET/MR device.

Bakula A, Patriki D, von Felten E, Benetos G, ... Buechel RR, Fuchs TA
Background
No methodology is available to distinguish truly reduced myocardial flow reserve (MFR) in positron emission tomography myocardial perfusion imaging (PET MPI) from seemingly impaired MFR due to inadequate adenosine response. The adenosine-induced splenic switch-off (SSO) sign has been proposed as a potential marker for adequate adenosine response in cardiac magnetic resonance (CMR). We assessed the feasibility of detecting SSO in nitrogen-13 ammonia PET MPI using SSO in CMR as the standard of reference.
Methods and results
Fifty patients underwent simultaneous CMR and PET MPI on a hybrid PET/MR device with co-injection of a gadolinium-based contrast agent and nitrogen-13 ammonia during rest and adenosine-induced stress. In CMR, SSO was assessed visually (positive vs negative SSO) and quantitatively by calculating the ratio of the peak signal intensity of the spleen during stress over rest (SIR). In PET MPI, the splenic signal activity ratio (SAR) was calculated as the maximal standard uptake value of the spleen during stress over rest. The median SIR was significantly lower in patients with positive versus negative SSO in CMR (0.57 [IQR 0.49 to 0.62] vs 0.89 [IQR 0.76 to 0.98]; P < .001). Similarly, median SAR in PET MPI was significantly lower in patients with positive versus negative SSO (0.40 [IQR 0.32 to 0.45] vs 0.80 [IQR 0.47 to 0.98]; P < .001).
Conclusion
Similarly to CMR, SSO can be detected in nitrogen-13 ammonia PET MPI. This might help distinguish adenosine non-responders from patients with truly impaired MFR due to microvascular dysfunction or multivessel coronary artery disease.



J Nucl Cardiol: 21 Dec 2020; epub ahead of print

Diagnostic value of FDG PET/CT imaging in patients with surgically managed infective endocarditis: results of a retrospective analysis at a tertiary center.

Sag SJM, Menhart K, Grosse J, Hitzenbichler F, ... Maier LS, Sag CM
Background
We assessed the diagnostic value of FDG PET/CT in a real-world cohort of patients with surgically managed infective endocarditis (IE).
Methods
We performed a retrospective analysis of all patients hospitalized in a tertiary IE referral medical center from January 2014 to October 2018 fulfilling the following criteria: ICD-10 code for IE and OPS code for both, heart surgery and FDG PET/CT.
Results
Final analysis included 29 patients, whereof 28 patients had surgically proven IE. FDG PET/CT scan was true-positive in 15 patients (sensitivity (SEN) 56%) and false-negative in 12 patients. Combination of Duke criteria (DC) with FDG PET/CT scan resulted in gain of SEN for all patients with confirmed IE (SEN of DC 79% vs SEN of combination DC and FDG PET/CT 89%), driven by a relevant gain in PVE patients only (SEN of DC 78% vs SEN of combination DC and FDG PET/CT 94%). Interestingly, higher prosthesis age was observed in patients with false-negative scans.
Conclusions
We found a SEN of 56% for FDG PET/CT in a real-world cohort of patients with surgically proven IE which was associated with a 16% gain of IE diagnosis in patients with PVE when combined with DC.



J Nucl Cardiol: 21 Dec 2020; epub ahead of print

It\'s a small world after all: A Canadian resident\'s perspective on COVID-19.

Sutherland DEK

COVID-19 has infected millions of people, with an estimated total dead in the hundreds of thousands. This has significantly impacted health care, including who is delivering it, how it is delivered, and how it is taught. This article describes challenges of the COVID-19 pandemic from the perspective of a Canadian nuclear medicine resident, including new risks with nuclear imaging, navigating new and sometimes challenging guidelines, as well as working and living within the confines of social distancing.



J Nucl Cardiol: 29 Nov 2020; 27:2283-2286

Molecular imaging in nuclear cardiology: Pathways to individual precision medicine.

Glasenapp A, Hess A, Thackeray JT

Growth of molecular imaging bears potential to transform nuclear cardiology from a primarily diagnostic method to a precision medicine tool. Molecular targets amenable for imaging and therapeutic intervention are particularly promising to facilitate risk stratification, patient selection and exquisite guidance of novel therapies, and interrogation of systems-based interorgan communication. Non-invasive visualization of pathobiology provides valuable insights into the progression of disease and response to treatment. Specifically, inflammation, fibrosis, and neurohormonal signaling, central to the progression of cardiovascular disease and emerging therapeutic strategies, have been investigated by molecular imaging. As the number of radioligands grows, careful investigation of the binding properties and added-value of imaging should be prioritized to identify high-potential probes and facilitate translation to clinical applications. In this review, we discuss the current state of molecular imaging in cardiovascular medicine, and the challenges and opportunities ahead for cardiovascular molecular imaging to navigate the path from diagnosis to prognosis to personalized medicine.



J Nucl Cardiol: 29 Nov 2020; 27:2195-2201

The application of molecular imaging to advance translational research in chronic inflammation.

Zhou W, Dey A, Manyak G, Teklu M, ... Teague H, Mehta NN

Over the past several decades, molecular imaging techniques to assess cellular processes in vivo have been integral in advancing our understanding of disease pathogenesis. F-fluorodeoxyglucose (18-FDG) positron emission tomography (PET) imaging in particular has shaped the field of atherosclerosis research by highlighting the importance of underlying inflammatory processes that are responsible for driving disease progression. The ability to assess physiology using molecular imaging, combining it with anatomic delineation using cardiac coronary angiography (CCTA) and magnetic resonance imaging (MRI) and lab-based techniques, provides a powerful combination to advance both research and ultimately clinical care. In this review, we demonstrate how molecular imaging studies, specifically using 18-FDG PET, have revealed that early vascular disease is a systemic process with multiple, concurrent biological mechanisms using inflammatory diseases as a basis to understand early atherosclerotic mechanisms in humans.



J Nucl Cardiol: 25 Nov 2020; epub ahead of print

Single-photon cardiac imaging in patients with cardiac implantable electrical devices.

Valzania C, Bonfiglioli R, Fallani F, Martignani C, ... Fanti S, Galiè N

Nuclear imaging techniques like single-photon emission computed tomography (SPECT) and radionuclide angiography have wide applications in patients receiving a cardiac implantable electrical device (CIED), who cannot usually undergo cardiac magnetic resonance. Our aim was to provide an update of single-photon imaging clinical applications, with a specific focus on CIED recipients. SPECT imaging is commonly used in CIED patients to assess myocardial perfusion, but it can also be used to evaluate myocardial viability, which is an important predictor of LV function improvement by cardiac resynchronization therapy (CRT). Radionuclide angiography has shown higher temporal resolution and reproducibility than SPECT in the evaluation of cardiac function and dyssynchrony. Left ventricular dyssynchrony as assessed by radionuclide angiography with phase analysis may be reliably used for CRT patient selection and evaluation of CRT response. SPECT imaging with meta-iodo-benzyl-guanidine allows for cardiac sympathetic innervation examination, which may be used for prognostic stratification of heart failure patients and prediction of ventricular tachyarrhythmias. Finally, promising results in CIED infection diagnosis have been shown by SPECT with radiolabeled autologous white blood cells.



J Nucl Cardiol: 24 Nov 2020; epub ahead of print

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. F-fluorodeoxyglucose (F-FDG), a radiolabeled glucose analog, is retained by cells in proportion to their glycolytic activity. While F-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, F-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, F-FDG-PET/computed tomography (CT) imaging facilitates evaluation of disease pathways that span multiple organ systems. Within this paradigm, F-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 F-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: 16 Nov 2020; epub ahead of print

Gating failure can result in underestimation of cardiac function in myocardial perfusion scintigraphy.

Villagran Asiares A, Yakushev I, Nekolla SG

Here, we present a case with a pacemaker due to an atrioventricular (AV) block 2 Mobitz type, in whom a gating failure resulted in a relevant underestimation of cardiac function in myocardial perfusion scintigraphy. A set of quality control steps for gating errors is proposed.



J Nucl Cardiol: 10 Nov 2020; epub ahead of print

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 FFR) 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: 10 Nov 2020; epub ahead of print

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. F-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: 10 Nov 2020; epub ahead of print

Clinical and gated SPECT MPI parameters associated with super-response to cardiac resynchronization therapy.

Mesquita CT, Peix A, de Amorim Fernandes F, Giubbini R, ... Paez D, Garcia EV
Purpose
We sought to evaluate the behavior of cardiac mechanical synchrony as measured by phase SD (PSD) derived from gated MPI SPECT (gSPECT) in patients with super-response after CRT and to evaluate the clinical and imaging characteristics associated with super-response.
Methods
158 subjects were evaluated with gSPECT before and 6 months after CRT. Patients with an improvement of LVEF > 15% and NYHA class I/II or reduction in LV end-systolic volume > 30% and NYHA class I/II were labeled as super-responders (SR).
Results
34 patients were classified as super-responders (22%) and had lower PSD (32° ± 17°) at 6 months after CRT compared to responders (45° ± 24°) and non-responders 46° ± 28° (P = .02 for both comparisons). Regression analysis identified predictors independently associated with super-response to CRT: absence of previous history of CAD (odds ratio 18.7; P = .002), absence of diabetes mellitus (odds ratio 13; P = .03), and history of hypertension (odds ratio .2; P = .01).
Conclusion
LV dyssynchrony after CRT implantation, but not at baseline, was significantly better among super-responders compared to non-super-responders. The absence of diabetes, absence of CAD, and history of hypertension were independently associated with super-response after CRT.



J Nucl Cardiol: 04 Nov 2020; epub ahead of print

Non-traditional factors affecting referral for coronary angiography following SPECT myocardial perfusion imaging.

Gowdar S, Hussain N, Ahlberg AW, Elsadany M, ... Silverman D, Duvall WL
Background
The use of myocardial perfusion imaging (MPI) in the management of coronary artery disease (CAD) is well established. Although prior studies have shown disparities in the use of invasive angiography in patients with acute MI, data on factors affecting referral to angiography post-MPI are lacking. We sought to evaluate the primary determinants of referral to invasive angiography post-MPI and specifically assess the role of non-traditional non-clinical factors such as race/ethnicity, socioeconomic factors, insurance status, and marital status.
Methods
All patients without known CAD who underwent stress SPECT MPI over 15 years were reviewed and the performance of coronary angiography within 90 days of their MPI was recorded. Multiple factors were analyzed for an association with referral to angiography, including exercise and MPI results, baseline demographics, traditional cardiac risk factors, and non-traditional factors such as ethnicity, insurance, marital and socioeconomic status. In a secondary analysis, these factors were assessed with regard to abnormal MPI results.
Results
Out of 27,895 total patients, 2,150 (7.7%) underwent invasive coronary angiography. On multivariate analysis, inpatient location, positive ECG response, and abnormal MPI results were the strongest predictors of angiography. Non-traditional factors such as race/ethnicity and insurance status had a significant association with referral to angiography with Caucasians (OR 1.42, 95% CI 1.18-1.71, P < .0001) and those with private insurance (OR 1.35, 95% CI 1.13-1.62, P = .001) or Medicare (OR 1.30, 95% CI 1.08-1.56, P = .006) having higher rates of angiography despite controlling for traditional risk factors and test results.
Conclusion
Our study results indicate that non-traditional factors such as race/ethnicity and insurance status influence patient management decisions and impact the performance of downstream cardiac invasive testing after stress MPI. Higher rates of angiography in Caucasians, privately insured and Medicare patients were seen despite controlling for traditional risk factors and abnormal test results. Further research is needed to better understand these disparities, especially in the current healthcare environment.



J Nucl Cardiol: 04 Nov 2020; epub ahead of print

Automated abstraction of myocardial perfusion imaging reports using natural language processing.

Zheng C, Sun BC, Wu YL, Ferencik M, ... Musigdilok VV, Sharp AL
Background
Findings and interpretations of myocardial perfusion imaging (MPI) studies are documented in free-text MPI reports. MPI results are essential for research, but manual review is prohibitively time consuming. This study aimed to develop and validate an automated method to abstract MPI reports.
Methods
We developed a natural language processing (NLP) algorithm to abstract MPI reports. Randomly selected reports were double-blindly reviewed by two cardiologists to validate the NLP algorithm. Secondary analyses were performed to describe patient outcomes based on abstracted-MPI results on 16,957 MPI tests from adult patients evaluated for suspected ACS.
Results
The NLP algorithm achieved high sensitivity (96.7%) and specificity (98.9%) on the MPI categorical results and had a similar degree of agreement compared to the physician reviewers. Patients with abnormal MPI results had higher rates of 30-day acute myocardial infarction or death compared to patients with normal results. We identified issues related to the quality of the reports that not only affect communication with referring physicians but also challenges for automated abstraction.
Conclusion
NLP is an accurate and efficient strategy to abstract results from the free-text MPI reports. Our findings will facilitate future research to understand the benefits of MPI studies but requires validation in other settings.



J Nucl Cardiol: 04 Nov 2020; epub ahead of print

Effect of PET-CT misalignment on the quantitative accuracy of cardiac O-water PET.

Nordström J, Harms HJ, Kero T, Ebrahimi M, Sörensen J, Lubberink M
Background
Quantification of myocardial blood flow (MBF) with PET requires accurate attenuation correction, which is performed using a separate CT. Misalignment between PET and CT scans has been reported to be a common problem. The purpose of the present study was to assess the effect of PET CT misalignment on the quantitative accuracy of cardiac O-water PET.
Methods
Ten clinical patients referred for evaluation of ischemia and assessment of MBF with O-water were included in the study. Eleven different misalignments between PET and CT were induced in 6 different directions with 10 and 20 mm amplitudes: caudal (+Z), cranial (- Z), lateral (±X), anterior (+Y), and anterior combined with cranial (+ Y and - Z). Blood flow was quantified from rates of washout (MBF) and uptake (transmural MBF, MBFt) for the whole left ventricle and the three coronary territories. The results from all misalignments were compared to the original scan without misalignment.
Results
MBF was only minorly affected by misalignments, but larger effects were seen in MBFt. On the global level, average absolute deviation across all misalignments for MBF was 1.7% ± 1.4% and for MBFt 5.4% ± 3.2 Largest deviation for MBF was - 4.8% ± 5.8% (LCX, X + 20) and for MBFt - 19.3% ± 9.6% (LCX, X + 20). In general, larger effects were seen in LAD and LCX compared to in RCA.
Conclusion
The quantitative accuracy of MBF from O-water PET, based on the washout of the tracer, is only to a minor extent affected by misalignment between PET and CT.



J Nucl Cardiol: 03 Nov 2020; epub ahead of print

Comparison of 18F-sodium fluoride positron emission tomography imaging and 99mTc-pyrophosphate in cardiac amyloidosis.

Zhang LX, Martineau P, Finnerty V, Giraldeau G, ... Harel F, Pelletier-Galarneau M
Background
Pyrophosphate (PYP) scintigraphy provides high diagnostic accuracy for the detection of transthyretin (ATTR) cardiac amyloidosis (CA). There has recently been emerging interest in using 18F-sodium fluoride (NaF) for this application, yet its sensitivity has never been directly compared to that of PYP, the current molecular gold standard
Methods:
Twelve subjects with ATTR-CA and 5 controls referred for PYP-SPECT were prospectively enrolled. 18F-NaF PET/CT scans were performed at 1 and 3 hours. Qualitative and quantitative analyses of the images were performed, and the sensitivity of 18F-NaF PET/CT and PYP-SPECT were compared
Results:
Visual interpretation of NaF PET/CT yielded a sensitivity of 0.25 (95% CI 0.089 to 0.53) for the detection of ATTR-CA, which is significantly inferior to that of PYP-SPECT/CT (100%, P = .016). Visual interpretation at 3 hours yielded a similar sensitivity of 0.30 (95% CI 0.11 to 0.60, P  = 1.00). There were no false-positive NaF PET studies. Mean target-to-background ratio (TBRmean) at 1h did not differ significantly (P = .21) in ATTR-CA subjects (0.83 ± 0.15) compared to controls (0.72 ± 0.15). Receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.69 ± 0.16 (95% CI 0.37 to 1.00, P = .23).
Conclusion
With qualitative and quantitative analyses, sensitivity of NaF PET/CT is significantly inferior to that of PYP-SPECT for the diagnosis of ATTR-CA.



J Nucl Cardiol: 03 Nov 2020; epub ahead of print

Prognostic value of integrative analysis of electrical and mechanical dyssynchrony in patients with acute heart failure.

Zhou Y, He Z, Liao S, Liu Y, ... Li X, Zhou W
Background
Left ventricular mechanical dyssynchrony has been shown to provide significant clinical values for chronic heart failure (HF) and cardiac resynchronization therapy (CRT). The purpose of this study was to evaluate whether electrical dyssynchrony combined with mechanical dyssynchrony has an incremental benefit over electrical dyssynchrony or mechanical dyssynchrony alone to predict clinical events in patients with acute heart failure (AHF).
Methods
Ninety-six AHF patients who received standard 12-lead ECG, gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), and echocardiography were enrolled. Thirty-two normal subjects were collected as the control group to get the normal database of mechanical dyssynchrony. The end point is the composite of all-cause death and heart transplantation. Electrical dyssynchrony was defined as QRS duration > 120 ms. Mechanical dyssynchrony was defined as > mean + 2 × SD phase standard deviation (PSD) or phase bandwidth (PBW) based on our normal database.
Results
During the follow-up of 28 ± 10 months, complete data were obtained in 92 patients. 26 (28.3%) Patients who reached the end point were classified into the event group. There were no significant differences in PSD or PBW between the event and non-event groups. However, PBW > 77.76° was independently associated with the end point in the univariate and multivariate analysis (hazard ratio 2.92, 95% confidence interval 1.00-8.47, P = .049; hazard ratio 3.89, 95% confidence interval 1.01-14.97, P = .048). The Kaplan-Meier curve with a log-rank test showed that the end point rate was significantly higher in the patients with PBW > 77.76° (log-rank P = .039). Moreover, the ROC curve analysis showed that the area under the curve (AUC) for predicting end point events by the integrative analysis of QRS > 120 ms and PBW > 77.76° was significantly improved compared to QRS duration > 120 ms (AUC: 0.75 vs 0.68, P = .001) or PBW > 77.76° (AUC: 0.75 vs 0.62, P = .049), respectively. The model of combined electrical and mechanical dyssynchrony yielded a further significantly improved risk prediction for adverse events in the global χ.
Conclusions
The combination of QRS duration > 120 ms and PBW > 77.76° was an independent predictor of all-cause death and heart transplantation in AHF patients. The integrative analysis of electrical and mechanical dyssynchrony provides incremental prognostic value for clinical use.



J Nucl Cardiol: 03 Nov 2020; epub ahead of print

Investigating the genetic characteristics of CAD: Is there a role for myocardial perfusion imaging techniques?

Angelidis G, Valotassiou V, Satra M, Psimadas D, ... Kollia P, Georgoulias P

Several environmental and genetic factors have been found to influence the development and progression of coronary artery disease (CAD). Although the effects of the environmental hazards on CAD pathophysiology are well documented, the genetic architecture of the disease remains quite unclear. A number of single-nucleotide polymorphisms have been identified based on the results of the genome-wide association studies. However, there is a lack of strong evidence regarding molecular causality. The minority of the reported predisposing variants can be related to the conventional risk factors of CAD, while most of the polymorphisms occur in non-protein-coding regions of the DNA. However, independently of the specific underlying mechanisms, genetic information could lead to the identification of a population at higher genetic risk for the long-term development of CAD. Myocardial single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are functional imaging techniques that can evaluate directly myocardial perfusion, and detect vascular and/or endothelial dysfunction. Therefore, these techniques could have a role in the investigation of the underlying mechanisms associated with the identified predisposing variants, advancing our understanding regarding molecular causality. In the population at higher genetic risk, myocardial SPECT or PET could provide important evidence through the early depiction of sub-clinical dysfunctions, well before any atherosclerosis marker could be identified. Notably, SPECT and PET techniques have been already used for the investigation of the functional consequences of several CAD-related polymorphisms, as well as the response to certain treatments (statins). Furthermore, therefore, in the clinical setting, the combination of genetic evidence with the findings of myocardial SPECT, or PET, functional imaging techniques could lead to more efficient screening methods and may improve decision making with regard to the diagnostic investigation and patients\' management.



J Nucl Cardiol: 02 Nov 2020; epub ahead of print

Simultaneous assessment of microcalcifications and morphological criteria of vulnerability in carotid artery plaque using hybrid F-NaF PET/MRI.

Mechtouff L, Sigovan M, Douek P, Costes N, ... Berthezene Y, Nighoghossian N
Background
Previous studies have suggested the role of microcalcifications in plaque vulnerability. This exploratory study sought to assess the potential of hybrid positron-emission tomography (PET)/magnetic resonance imaging (MRI) using F-sodium fluoride (F-NaF) to check simultaneously F-NaF uptake, a marker of microcalcifications, and morphological criteria of vulnerability.
Methods and results
We included 12 patients with either recently symptomatic or asymptomatic carotid stenosis. All patients underwent F-NaF PET/MRI. F-NaF target-to-background ratio (TBR) was measured in culprit and nonculprit (including contralateral plaques of symptomatic patients) plaques as well as in other arterial walls. Morphological criteria of vulnerability were assessed on MRI. Mineral metabolism markers were also collected. F-NaF uptake was higher in culprit compared to nonculprit plaques (median TBR 2.6 [2.2-2.8] vs 1.7 [1.3-2.2]; P = 0.03) but was not associated with morphological criteria of vulnerability on MRI. We found a positive correlation between F-NaF uptake and calcium plaque volume and ratio but not with circulating tissue-nonspecific alkaline phosphatase (TNAP) activity and inorganic pyrophosphate (PPi) levels. F-NaF uptake in the other arterial walls did not differ between symptomatic and asymptomatic patients.
Conclusions
F-NaF PET/MRI may be a promising tool for providing additional insights into the plaque vulnerability.



J Nucl Cardiol: 02 Nov 2020; epub ahead of print

The diagnostic value of SPECT CZT quantitative myocardial blood flow in high-risk patients.

Zavadovsky KV, Mochula AV, Maltseva AN, Boshchenko AA, ... Liga R, Gimelli A
Background
The objective of this study was to evaluate the accuracy of global MBF and MFR quantitation performed by myocardial perfusion scintigraphy (MPS) for the detection of multivessel coronary artery disease (CAD).
Methods
52 CAD patients underwent CZT MPS, with the evaluation of MBF and MFR, followed by invasive coronary angiography (ICA). According to MPS and ICA results, all patients were divided into three groups: (1) non-obstructive CAD and normal MPS scan (control group) (n = 7), (2) one vessel disease (1VD) (n = 16), (3) multivessel disease (MVD) (n = 29).
Results
Global absolute MBF and MFR were significantly reduced in MVD patients as compared to those with 1VD [0.93 (IQR 0.76; 1.39) vs 1.94 (1.37; 2.21) mL·min·g, P = .00012] and [1.4 (IQR 1.02; 1.85) vs 2.3 (1.8; 2.67), P = . 0 004], respectively. The Syntax score correlated with global stress MBF (ρ = - 0.64; P < .0001) and MFR (ρ = - 0.53; P = .0003). ROC analysis showed higher sensitivity and specificity for stress MBF and MFR compared with semiquantitative MPS stress evaluation. Multivariate regression analysis showed that only stress MBF [OR (95% CI) 0.59 (0.42-0.82); P < .0003] was an independent predictor of MVD.
Conclusions
Quantitative myocardial blood flow values assessed with the use of CZT camera may identify high-risk patients, such as those with multivessel disease.



J Nucl Cardiol: 22 Oct 2020; epub ahead of print

Prognostic significance of incidental suspected transthyretin amyloidosis on routine bone scintigraphy.

Suomalainen O, Pilv J, Loimaala A, Mätzke S, Heliö T, Uusitalo V
Background
Transthyretin amyloidosis (ATTR) is an occasional incidental finding on bone scintigraphy. We studied its prognostic impact in elderly patients.
Methods
The study population consisted of 2000 patients aged over 70 years who underwent bone scintigraphies with clinical indications in three nuclear medicine departments (Kymenlaakso, Jorvi and Meilahti hospitals) in Finland. All studies were performed using Technetium labeled hydroxymethylene diphosphonate (HMDP). ATTR was suspected in patients with ≥grade 2 Perugini grade uptake (grade 0-3). Heart-to-contralateral ratio (H/CL) of ≥ 1.30 was considered positive for ATTR. The overall and cardiovascular mortality were obtained from the Finnish National Statistical Service.
Results
There were a total of 1014 deaths (51%) and 177 cardiovascular deaths (9%) during median follow-up of 4 ± 2 years. ATTR was suspected in 69 patients (3.6%) of which 54 (2.7%) had grade 2 and 15 (.8%) had grade 3 uptake and in 47 patients (2.4%) by H/CL ratio. In multivariate analyses age, bone metastasis, H/CL ratio and grade 3 uptake were independent predictors of overall and cardiovascular mortality. Grade 2 uptake was a predictor of cardiovascular mortality.
Conclusions
A suspected ATTR as an incidental finding on bone scintigraphy predicts elevated overall and cardiovascular mortality in elderly patients.



J Nucl Cardiol: 21 Oct 2020; epub ahead of print

Spectrum of radionuclide perfusion study abnormalities in takotsubo cardiomyopathy.

Anderson JL, Horne BD, Le VT, Bair TL, ... Muhlestein JB, Knowlton KU
Background
Takotsubo (stress) cardiomyopathy (TCM) is characterized by transient apical left ventricular dysfunction precipitated by emotional or physical stress. Its presentation makes it difficult to differentiate from an acute coronary syndrome. A suggestive echocardiogram plus normal coronary angiography most often are used for diagnosis. Radionuclide perfusion study (RPS) findings in TCM, including by positron emission tomography (PET), have been poorly characterized.
Methods and results
Intermountain Healthcare electronic medical records were searched from 2009 to 2019 for patients with a discharge diagnosis of TCM, stress CM, or takotsubo syndrome. 16 TCM patients with an RPS, including by PET in 8, were identified: 13 (81%) were women; age averaged 72 years (50-89 years); 14 had an identified stressor. TCM diagnosis was definite in 11 and probable/possible in 5. RPS was abnormal in 11, with 9 showing an apical perfusion deficit, whereas angiography in 14 showed normal coronaries in 12 and non-obstructive disease in 2. Echo ejection fraction averaged 41% (29%-60%); an apical wall motion abnormality was present in 14 (88%). Troponin elevations were noted in 14/15. The presenting ECG was abnormal is 14, frequently showing ST-T-wave abnormalities. 13 patients were discharged on a beta-blocker. Follow-up echo (in 12) showed recovered ejection fraction in 9 and recovered apical wall motion in 11.
Conclusions
Despite having normal or non-obstructive epicardial coronary arteries on angiography, TCM patients frequently present with apical wall motion abnormalities and matching RPS perfusion defects. These findings suggest microvascular abnormalities, whose pathophysiology, temporal course, and clinical implications should be the subject of further investigation.



J Nucl Cardiol: 21 Oct 2020; epub ahead of print

Assessment of left and right ventricular functional parameters using dynamic dual-tracer [N]NH3 and [F]FDG PET/MRI.

Rasul S, Beitzke D, Wollenweber T, Rausch I, ... Loewe C, Hacker M
Background
Cardiac positron emission tomography/magnetic resonance imaging (PET/MRI) can assess various cardiovascular diseases. In this study, we intra-individually compared right (RV) and left ventricular (LV) parameters obtained from dual-tracer PET/MRI scan.
Methods
In 22 patients with coronary heart disease (69 ± 9 years) dynamic [N]NH (NH) and [F]FDG (FDG) PET scans were acquired. The first 2 minutes were used to calculate LV and RV first-pass ejection fraction (FPEF). Additionally, LV end-systolic (LVESV) and end-diastolic (LVEDV) volume and ejection fraction (LVEF) were calculated from the early (EP) and late-myocardial phases (LP). MRI served as a reference.
Results
RVFPEF and LVFPEF from FDG and NH as well as RVEF and LVEF from MRI were (28 ± 11%, 32 ± 15%), (32 ± 11%, 41 ± 14%) and (42 ± 16%, 45 ± 19%), respectively. LVESV, LVEDV and LVEF from EP FDG and NH in 8 and 16 gates were [71 (15 to 213 mL), 98 (16 to 241 mL), 32 ± 17%] and [50 (17 to 206 mL), 93 (13 to 219 mL), 36 ± 17%] as well as [60 (19 to 360 mL), 109 (56 to 384 mL), 41 ± 22%] and [54 (16 to 371 mL), 116 (57 to 431 mL), 46 ± 24%], respectively. Moreover, LVESV, LVEDV and LVEF acquired from LP FDG and NH were (85 ± 63 mL, 138 ± 63 mL, 47 ± 19%) and (79 ± 56 mL, 137 ± 63 mL, 47 ± 20%), respectively. The LVESV, LVEDV from MRI were 93 ± 66 mL and 153 ± 71 mL, respectively. Significant correlations were observed for RVFPEF and LVFPEF between FDG and MRI (R = .51, P = .01; R = .64, P = .001), respectively. LVESV, LVEDV, and LVEF revealed moderate to strong correlations to MRI when they acquired from EP FDG and NH in 16 gates (all R > .7, P = .000). Similarly, all LV parameters from LP FDG and NH correlated good to strongly positive with MRI (all R > .7, and P < .001), except EDV from NH3 weakly correlated to EDV of MRI (R = .54, P < .05). Generally, Bland-Altman plots showed good agreements between PET and MRI.
Conclusions
Deriving LV and RV functional values from various phases of dynamic NH and FDG PET is feasible. These results could open a new perspective for further clinical applications of the PET examinations.



J Nucl Cardiol: 21 Oct 2020; epub ahead of print

Absolute Resting N-Ammonia PET Myocardial Blood Flow for Predicting Myocardial Viability and Recovery of Ventricular Function after Coronary Artery Bypass Grafting.

Wang J, Li JM, Li S, Hsu B
Objective
We aimed to evaluate the feasibility of resting myocardial blood flow (rMBF), quantified with dynamic 13 N-Ammonia (NH) PET, for identifying myocardial viability and predicting improvement of left ventricular ejection fraction (LVEF) after coronary artery bypass grafting (CABG).
Methods
Ninety-three patients with coronary artery disease (CAD) and chronic LVEF < 45%, scheduled for CABG, had dynamic NH PET and F-FDG PET imaging. The perfusion/metabolism polar maps were categorized in four patterns: normal (N), mismatch (M1), match (M2) and reverse mismatch (RM). The value of rMBF for identifying viable myocardium (M1, RM) and post CABG improvement of LVEF≥8% was analyzed by receiver operating characteristic (ROC) curves. Correlations of rMBF in segments to ΔLVEF post CABG were verified.
Results
Mean rMBFs were significantly different (N=0.60±0.14; M1=0.44±0.07, M2=0.34±0.08, RM=0.53±0.09 ml/min/g, P<0.001). The optimal rMBF cutoff to identify viable myocardium was 0.42 ml/min/g (sensitivity=88.3%, specificity=82.0%) and 0.43 ml/min/g for predicting improvement of LVEF ≥8% (74.6%, 80.0%). The extent and rMBF of combined M1/RM demonstrated a moderate to high correlation to improved LVEF (r=0.78, 0.71, P<0.001).
Conclusion
Resting MBF, derived by dynamic NH PET, may be positioned as a supplement to F-FDG PET imaging for assessing the presence of viable myocardium and predicting potential improvement of LVEF after CABG.



J Nucl Cardiol: 20 Oct 2020; epub ahead of print

Prognostic value of absent left ventricular ejection fraction reserve with regadenoson SPECT MPI.

Smith P, Farag A, Bhambhvani P, Iskandrian A, Hage FG
Background
An absent left ventricular ejection fraction (LVEF) reserve with vasodilator stress with PET cardiac imaging has been shown to provide significant independent and incremental value to the perfusion images for prediction of future cardiovascular adverse events. However, the prognostic value of LVEF reserve has not been well characterized with SPECT myocardial perfusion imaging (MPI).
Methods
We studied 858 consecutive patients with normal and abnormal perfusion pattern with regadenoson SPECT MPI. Change in LVEF was calculated as post-stress LVEF-rest LVEF. Absent LVEF reserve was defined as a drop in LVEF by 5% or more on the post-stress images. The primary outcome was a composite of cardiac death, non-fatal myocardial infarction and late coronary revascularization.
Results
An absent LVEF reserve was more common in patients with abnormal vs normal MPI (31% vs 19%, P = .001). During a median follow-up of 32 months, the primary outcome was experienced by 31% of the study population. An absent LVEF reserve was not associated with an increased risk of the primary outcome in patients with normal (hazard ratio 1.1, 95% CI .4-2.7, P = .8) or abnormal (.75, .56-1.00, P = .05) MPI. There was no significant correlation between extent of ischemia and post-stress change in LVEF (Pearson r = - .072, P = .07).
Conclusions
In patients undergoing regadenoson SPECT MPI, absent LVEF reserve is not associated with worse cardiac outcomes. Thus, routine reporting of both post-stress and rest LVEF measurements in this setting may not be necessary.



J Nucl Cardiol: 20 Oct 2020; epub ahead of print