Automated quantitative analysis of CZT SPECT stratifies cardiovascular risk in the obese population: Analysis of the REFINE SPECT registry.

Klein E, Miller RJH, Sharir T, Einstein AJ, ... Berman DS, Slomka PJ
Background
Obese patients constitute a substantial proportion of patients referred for SPECT myocardial perfusion imaging (MPI), presenting a challenge of increased soft tissue attenuation. We investigated whether automated quantitative perfusion analysis can stratify risk among different obesity categories and whether two-view acquisition adds to prognostic assessment.
Methods
Participants were categorized according to body mass index (BMI). SPECT MPI was assessed visually and quantified automatically; combined total perfusion deficit (TPD) was evaluated. Kaplan-Meier and Cox proportional hazard analyses were used to assess major adverse cardiac event (MACE) risk. Prognostic accuracy for MACE was also compared.
Results
Patients were classified according to BMI: BMI < 30, 30 ≤ BMI < 35, BMI ≥ 35. In adjusted analysis, each category of increasing stress TPD was associated with increased MACE risk, except for 1% ≤ TPD < 5% and 5% ≤ TPD < 10% in patients with BMI ≥ 35. Compared to visual analysis, single-position stress TPD had higher prognostic accuracy in patients with BMI < 30 (AUC .652 vs .631, P < .001) and 30 ≤ BMI < 35 (AUC .660 vs .636, P = .027). Combined TPD had better discrimination than visual analysis in patients with BMI ≥ 35 (AUC .662 vs .615, P = .003).
Conclusions
Automated quantitative methods for SPECT MPI interpretation provide robust risk stratification in the obese population. Combined stress TPD provides additional prognostic accuracy in patients with more significant obesity.



J Nucl Cardiol: 13 Sep 2020; epub ahead of print

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

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



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

Diagnostic utility of fusion F-fluorodeoxyglucose positron emission tomography/cardiac magnetic resonance imaging in cardiac sarcoidosis.

Okune M, Yasuda M, Soejima N, Kagioka Y, ... Miyazaki S, Iwanaga Y
Background
Although each F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE) has been used to diagnose cardiac sarcoidosis (CS), active CS is still misdiagnosed.
Methods
Active CS, diagnosed by PET alone, was defined as focal or focal on diffuse FDG uptake pattern. In fusion PET/CMR imaging, using a regional analysis with AHA 17-segment model, the patients were categorized into four groups: (1) PET-/LGE-, (2) PET+/LGE-, (3) PET+/LGE+, and (4) PET-/LGE+. PET+/LGE+ was defined as active CS.
Results
74 Patients with suspected CS were enrolled. Between PET alone and fusion PET/CMR imaging, 20 cases had mismatch evaluations of active CS, and most had diffuse or focal on diffuse FDG uptake pattern on PET alone imaging. 40 Patients fulfilled the 2016 the Japanese Circulation Society diagnostic criteria for CS. The interobserver diagnostic agreement was excellent (κ statistics 0.89) and the overall accuracy for diagnosing CS was 87.8% in fusion PET/CMR imaging, which were superior to those in PET alone imaging (0.57 and 82.4%, respectively). In a sub-analysis of diffuse and focal on diffuse patterns, the agreement (κ statistics 0.86) and overall accuracy (81.8%) in fusion PET/CMR imaging were still better.
Conclusions
Fusion PET/CMR imaging with regional analysis offered reliable and accurate diagnosis of CS, covering low diagnostic area by FDG-PET alone.



J Nucl Cardiol: 30 Sep 2020; epub ahead of print

18F-fluoride PET/MR in cardiac amyloid: A comparison study with aortic stenosis and age- and sex-matched controls.

Andrews JPM, Trivieri MG, Everett R, Spath N, ... Fayad ZA, Dweck MR
Objectives
Cardiac MR is widely used to diagnose cardiac amyloid, but cannot differentiate AL and ATTR subtypes: an important distinction given their differing treatments and prognoses. We used PET/MR imaging to quantify myocardial uptake of 18F-fluoride in ATTR and AL amyloid patients, as well as participants with aortic stenosis and age/sex-matched controls.
Methods
In this prospective multicenter study, patients were recruited in Edinburgh and New York and underwent 18F-fluoride PET/MR imaging. Standardized volumes of interest were drawn in the septum and areas of late gadolinium enhancement to derive myocardial standardized uptake values (SUV) and tissue-to-background ratio (TBR) after correction for blood pool activity in the right atrium.
Results
53 patients were scanned: 18 with cardiac amyloid (10 ATTR and 8 AL), 13 controls, and 22 with aortic stenosis. No differences in myocardial TBR values were observed between participants scanned in Edinburgh and New York. Mean myocardial TBR values in ATTR amyloid (1.13 ± 0.16) were higher than controls (0.84 ± 0.11, P = .0006), aortic stenosis (0.73 ± 0.12, P < .0001), and those with AL amyloid (0.96 ± 0.08, P = .01). TBR values within areas of late gadolinium enhancement provided discrimination between patients with ATTR (1.36 ± 0.23) and all other groups (e.g., AL [1.06 ± 0.07, P = .003]). A TBR threshold >1.14 in areas of LGE demonstrated 100% sensitivity (CI 72.25 to 100%) and 100% specificity (CI 67.56 to 100%) for ATTR compared to AL amyloid (AUC 1, P = .0004).
Conclusion
Quantitative 18F-fluoride PET/MR imaging can distinguish ATTR amyloid from other similar phenotypes and holds promise in improving the diagnosis of this condition.



J Nucl Cardiol: 29 Sep 2020; epub ahead of print

Prognostic value of myocardial perfusion imaging with D-SPECT camera in patients with ischemia and no obstructive coronary artery disease (INOCA).

Liu L, Abdu FA, Yin G, Xu B, ... Xu Y, Che W
Background
Myocardial perfusion imaging (MPI) with a novel D-SPECT camera maintains excellent prognostic value compared to conventional SPECT. However, information about the relationship between D-SPECT MPI and the prognosis in patients with ischemia and no obstructive coronary artery disease (INOCA) is limited. The objective of this study was to evaluate the prognostic value of MPI with D-SPECT in INOCA and obstructive coronary artery disease (CAD) patients.
Methods
All consecutive patients with suspected CAD and without prior CAD who underwent D-SPECT MPI and invasive coronary angiography within 3 months were considered. INOCA and obstructive CAD were defined as < 50% and ≥ 50% coronary stenosis, respectively. Patients were followed-up for the occurrence of major adverse cardiac events (MACE: cardiovascular death, nonfatal myocardial infarction, revascularization, stroke, heart failure and angina-related rehospitalization).
Results
Among 506 patients, 232 (45.8%) were INOCA patients. A total of 33.2% of the INOCA patients had abnormal D-SPECT MPI, whereas 77.7% of the obstructive CAD patients had abnormal D-SPECT MPI. In both groups, patients with abnormal D-SPECT MPI demonstrated higher MACE rates and lower survival free of MACE. In addition, patients with INOCA and abnormal D-SPECT MPI had a poor prognosis similar to that of the obstructive CAD patients. Cox regression analysis showed that the risk-adjusted hazard ratios for abnormal D-SPECT MPI were 2.55 [1.11-5.87] and 2.06 [1.03-4.10] in the INOCA and obstructive CAD patients, respectively.
Conclusions
D-SPECT MPI provides excellent prognostic information, with a more severe prognosis in patients with abnormal D-SPECT MPI. INOCA patients with abnormal D-SPECT MPI experience a poor prognosis similar to that of patients with obstructive CAD.



J Nucl Cardiol: 29 Sep 2020; epub ahead of print

The indications and utility of adjunctive imaging modalities for chronic total occlusion (CTO) intervention.

Allahwala UK, Brilakis ES, Kiat H, Ayesa S, ... Weaver JC, Bhindi R

Coronary chronic total occlusions (CTO) are common in patients undergoing coronary angiography, yet the optimal management strategy remains uncertain, with conflicting results from randomized trials. Appropriate patient selection and careful periprocedural planning are imperative for successful patient management. We review the role of adjunctive imaging modalities including myocardial perfusion imaging (MPI), cardiac magnetic resonance imaging (CMR), echocardiography and computed tomography coronary angiography (CTCA) in myocardial ischemic quantification, myocardial viability assessment, as well as procedural planning for CTO revascularization. An appreciation of the value, indications and limitations of these modalities prior to planned intervention are essential for optimal management.



J Nucl Cardiol: 05 Oct 2020; epub ahead of print

Normal myocardial perfusion despite a very high coronary calcium score.

Castro-Villacorta H, Ortiz-Velázquez JF, Preciado-Gutiérrez OU, Paz-Gómez R, Alemán-Villalobos R, Preciado-Anaya A

An exceptionally high coronary calcium score, greater than 10,000 UA, superior to any other found in the literature reviewed, was reported in an asymptomatic, adult man with hypertension, obesity and dyslipidemia, without myocardial ischemia and no significative coronary stenosis, associated to Glagov\'s phenomenon in the left coronary artery and an abdominal aortic aneurysm.



J Nucl Cardiol: 11 Oct 2020; epub ahead of print

Diagnostic performance of prone-only myocardial perfusion imaging versus coronary angiography in the detection of coronary artery disease: A systematic review and meta-analysis.

Mirshahvalad SA, Chavoshi M, Hekmat S
Study design
Although prone position is considered as a complementary protocol in myocardial perfusion imaging (MPI), there is no consensus on its capability to find coronary artery disease (CAD), independently. The primary aim of this review was to report pooled sensitivity and specificity for prone position MPI in detection of CAD. In addition, the results were compared to the supine position\'s performance.
Methods
Electronic bibliographic databases, The Cochrane Library, Web of Science (Science and Social Science Citation Index), Scopus, PubMed, and EMBASE until the end of June 2020 were searched. Studies were included based on the inclusion criteria of (1) evaluated the prone position MPI, (2) defined CAD with coronary angiography (CAG), using the threshold of ≥ 50% stenosis, (3) Adequate data were provided to extract the diagnostic performance. QUADAS-2 tool was utilized to assess the quality of included studies. Pooled sensitivity and specificity were calculated for prone and supine positions, separately. The hierarchical summary ROC curves were also drawn.
Results
Ten individual studies with the data of the 1490 patients for the prone position and 1138 patients for the supine position were included. Pooled sensitivity and specificity for the prone position were 83% and 79%, respectively. These results were calculated for the supine position as the sensitivity of 86% and specificity of 67%. The pooled sensitivity and specificity of the prone position in detecting the right coronary artery territory defects were 70% and 84%, in turn.
Conclusion
In the suspicion for the CAD, prone position with comparable sensitivity and higher specificity can be an acceptable alternative to the supine position as the standard method. Also, in the cases of possible defects in the RCA territory, prone position showed to be a superior standard.



J Nucl Cardiol: 05 Oct 2020; epub ahead of print

Psychological factors of suspect coronary microvascular dysfunction in patients undergoing SPECT imaging.

Bekendam MT, Vermeltfoort IAC, Kop WJ, Widdershoven JW, Mommersteeg PMC
Background
Patients with myocardial ischemia in the absence of obstructive coronary artery disease (CAD) often experience anginal complaints and are at risk of cardiac events. Stress-related psychological factors and acute negative emotions might play a role in these patients with suspect coronary microvascular dysfunction (CMD).
Methods and results
295 Patients (66.9 ± 8.7 years, 46% women) undergoing myocardial perfusion single-photon-emission computed tomography (MPI-SPECT), were divided as follows: (1) a non-ischemic reference group (n = 136); (2) patients without inducible ischemia, but with a history of CAD (n = 62); (3) ischemia and documented CAD (n = 52); and (4) ischemia and suspect CMD (n = 45). These four groups were compared with regard to psychological factors and acute emotions. Results revealed no differences between the groups in psychological factors (all P > .646, all effect sizes d < .015). State sadness was higher for patients with suspect CMD (16%) versus the other groups (P = .029). The groups did not differ in the association of psychological factors or emotions with anginal complaints (all P values > .448).
Conclusion
Suspect CMD was not associated with more negative psychological factors compared to other groups. State sadness was significantly higher for patients with suspect CMD, whereas no differences in state anxiety and other psychological factors were found.



J Nucl Cardiol: 05 Oct 2020; epub ahead of print

F-flutemetamol positron emission tomography in cardiac amyloidosis.

Papathanasiou M, Kessler L, Carpinteiro A, Hagenacker T, ... Luedike P, Rischpler C
Purpose
Bone-tracer scintigraphy has an established role in diagnosis of cardiac amyloidosis (CA) as it detects transthyretin amyloidosis (ATTR). Positron emission tomography (PET) with amyloid tracers has shown high sensitivity for detection of both ATTR and light-chain (AL) CA. We aimed to investigate the accuracy of F-flutemetamol in CA.
Methods
We enrolled patients with CA or non-amyloid heart failure (NA-HF), who underwent cardiac F-flutemetamol PET/MRI or PET/CT. Myocardial and blood pool standardized tracer uptake values (SUV) were estimated. Late gadolinium enhancement (LGE) and T1 mapping/ extracellular volume (ECV) estimation were performed.
Results
We included 17 patients (12 with CA, 5 with NA-HF). PET/MRI was conducted in 13 patients, while PET/CT was conducted in 4. LGE was detected in 8 of 9 CA patients. Global relaxation time and ECV were higher in CA (1448 vs. 1326, P = 0.02 and 58.9 vs. 33.7%, P = 0.006, respectively). Positive PET studies were demonstrated in 2 of 12 patients with CA (AL and ATTR). Maximal and mean SUV did not differ between groups (2.21 vs. 1.69, P = 0.18 and 1.73 vs. 1.30, P = 0.13).
Conclusion
Although protein-independent binding is supported by our results, the diagnostic yield of PET was low. We demonstrate here for the first time the low sensitivity of PET for CA.



J Nucl Cardiol: 05 Oct 2020; epub ahead of print

The diagnostic and prognostic value of near-normal perfusion or borderline ischemia on stress myocardial perfusion imaging.

Kassab K, Hussain K, Torres A, Iskander F, ... Khan R, Doukky R
Background
Data on the diagnostic and prognostic value of subtle abnormalities on myocardial perfusion imaging (MPI) are limited.
Methods and results
In a retrospective single-center cohort of patients who underwent regadenoson SPECT-MPI, near-normal MPI was defined as normal left ventricular ejection fraction (LVEF ≥ 50%) and a summed stress score (SSS) of 1-3 vs SSS = 0 in normal MPI. Borderline ischemia was defined as normal LVEF, SSS = 1-3, and a summed difference score (SDS) of 1 vs SDS = 0 in the absence of ischemia. Coronary angiography data within 6 months from MPI were tabulated. Patients were followed for cardiac death (CD), myocardial infarction (MI), coronary revascularization (CR), and Late CR (LCR) [> 90 days post MPI]. Among 6,802 patients (mean age, 62 ± 13 years; 42% men), followed for a mean of 2.5 ± 2.1 years, 4,398 had normal MPI, 2,404 had near-normal MPI, and 972 had borderline ischemia. Among patients who underwent angiography within 6 months, obstructive (≥ 70% or left main ≥ 50%) CAD was observed at higher rates among subjects with near-normal MPI (33.5% vs 25.5%; P = .049) and those with borderline ischemia (40.5% vs 25.8%; P = .004). During follow-up, 158 (2.3%) CD/MI, 246 (3.6%) CR, and 150 (2.2%) LCR were observed. Near-normal MPI (SSS = 1-3), compared to normal MPI (SSS = 0), was not associated with a significant difference in the risk of the composite endpoint of CD/MI (Hazard ratio [HR], 1.21; 95% confidence interval [CI], .88-1.66; P = .243) or LCR (HR 1.28; CI .93-1.78; P = .130), but was associated with a significant increase in the risk of CR (HR 1.91; CI 1.49-2.46; P < .001). Borderline ischemia (SDS = 1), compared to no ischemia (SDS = 0), was not associated with a significant difference in the risk of CD/MI [HR 1.09; CI .70-1.69; P = .693], but was associated with a significant increase in the risk of CR (HR 5.62; CI 3.08-10.25; P < .001) and LCR (HR 2.98; CI 1.36-6.53; P = .006).
Conclusion
Near-normal MPI and borderline ischemia on SPECT-MPI provide no significant prognostic information in predicting hard cardiac events but are associated with higher rates of obstructive angiographic CAD and coronary revascularizations.



J Nucl Cardiol: 08 Oct 2020; epub ahead of print

The prognostic implications of ST-segment and T-wave abnormalities in patients undergoing regadenoson stress SPECT myocardial perfusion imaging.

Khan MS, Arif AW, Doukky R
Background
The prognostic implications of ST-segment and T-wave (ST/T) abnormalities in patients undergoing stress SPECT-myocardial perfusion imaging (MPI) are not well defined.
Methods and results
This was a single-center, retrospective cohort study of consecutive patients who underwent regadenoson stress SPECT-MPI. Patients with baseline electrocardiogram (ECG) abnormalities that impede ST/T analysis or those with known coronary artery disease were excluded. Patients were categorized as having primary ST abnormalities, secondary ST/T abnormalities due to ventricular hypertrophy or right bundle branch block, T-wave abnormalities, or normal ECG. The primary outcome was major adverse cardiovascular events (MACE) defined as the composite of cardiac death or myocardial infarction. Among 6,059 subjects, 1912 (32%) had baseline ST/T abnormalities. During a mean follow-up of 2.3 ± 1.9 years, the incidence of MACE was significantly higher among patients with secondary ST/T abnormalities compared to those with normal ECG (HR 2.05; 95% confidence interval [CI], 1.04-4.05; P = 0.039). No significant difference in MACE was observed among patients with primary ST abnormalities (HR 1.64; CI 0.87-3.06; P = 0.124) or T-wave abnormalities (HR 1.15; CI 0.62-2.16; P = 0.658) compared with patients who had normal ECG. Among patients with secondary ST/T changes, abnormal MPI was not associated with a significant increase in MACE rates compared to normal MPI (HR 1.18; CI 0.31-4.58; P = 0.808). However, abnormal MPI was associated with higher MACE rates among patients with primary ST abnormalities (HR 4.50; CI 1.44-14.10; P = 0.005) and T-wave abnormalities (HR 3.74; CI 1.20-11.68; P = 0.015). Similarly, myocardial ischemia on regadenoson stress SPECT-MPI was not associated with a significant increase in MACE rates in patients with secondary ST/T abnormalities (HR 1.45; CI 0.38-5.61; P = 0.588), while it was associated with a higher incidence of MACE in patients with primary ST abnormalities (HR 3.012; CI 0.95-9.53; P = 0.049) and T-wave abnormalities (HR 5.06; CI 1.60-15.96; P = 0.002).
Conclusion
While patients with secondary ST/T abnormalities had significantly higher MACE risk, abnormal MPI or presence of myocardial ischemia on regadenoson SPECT-MPI in this group does not add prognostic information. Patients with primary ST abnormalities and T-wave abnormalities do not seem to have a significantly higher MACE risk compared to those with normal ECG; however, abnormal MPI or presence of myocardial ischemia, in these groups, correlates with higher MACE rates.



J Nucl Cardiol: 07 Oct 2020; epub ahead of print

Anger recall mental stress decreases I-metaiodobenzylguanidine (I-MIBG) uptake and increases heterogeneity of cardiac sympathetic activity in the myocardium in patients with ischemic cardiomyopathy.

Avendaño R, Hashemi-Zonouz T, Sandoval V, Liu C, ... Lampert R, Liu YH
Background
Acute psychological stressors such as anger can precipitate ventricular arrhythmias, but the mechanism is incompletely understood. Quantification of regional myocardial sympathetic activity with I-metaiodobenzylguanidine (I-mIBG) SPECT imaging in conjunction with perfusion imaging during mental stress may identify a mismatch between perfusion and sympathetic activity that may exacerbate a mismatch between perfusion and sympathetic activity that could create a milieu of increased vulnerability to ventricular arrhythmia.
Methods
Five men with ischemic cardiomyopathy (ICM), and five age-matched healthy male controls underwent serial I-mIBG and Tc-Tetrofosmin SPECT/CT imaging during an anger recall mental stress task and dual isotope imaging was repeated approximately 1 week later during rest. Images were reconstructed using an iterative reconstruction algorithm with CT-based attenuation correction. The mismatch of left ventricular myocardial I-mIBG and Tc-Tetrofosmin was assessed along with radiotracer heterogeneity and the I-mIBG heart-to-mediastinal ratios (HMR) were calculated using custom software developed at Yale.
Results
The hemodynamic response to mental stress was similar in both groups. The resting-HMR was greater in healthy control subjects (3.67 ± 0.95) than those with ICM (3.18 ± 0.68, P = .04). Anger recall significantly decreased the HMR in ICM patients (2.62 ± 0.3, P = .04), but not in normal subjects. The heterogeneity of I-mIBG uptake in the myocardium was significantly increased in ICM patients during mental stress (26% ± 8.23% vs. rest: 19.62% ± 9.56%; P = .01), whereas the Tc-Tetrofosmin uptake pattern was unchanged.
Conclusion
Mental stress decreased the I-mIBG HMR, increased mismatch between sympathetic activity and myocardial perfusion, and increased the heterogeneity of I-mIBG uptake in ICM patients, while there was no significant change in myocardial defect size or the heterogeneity of Tc-Tetrofosmin perfusion. The changes observed in this proof-of-concept study may provide valuable information about the trigger-substrate interaction and the potential vulnerability for ventricular arrhythmias.



J Nucl Cardiol: 07 Oct 2020; epub ahead of print

Mortality risk among patients undergoing exercise versus pharmacologic myocardial perfusion imaging: A propensity-based comparison.

Rozanski A, Gransar H, Hayes SW, Friedman JD, Thomson L, Berman DS
Background
The increased risk associated with pharmacologic versus exercise testing is obscured by the higher prevalence of clinical risk factors among pharmacologic patients. Thus, we assessed comparative mortality in a large risk factor-matched group of exercise versus pharmacologic patients undergoing stress/rest SPECT myocardial perfusion imaging (MPI).
Methods
39,179 patients undergoing stress/rest SPECT-MPI were followed for 13.3 ± 5.0 years for all-cause mortality (ACM). We applied propensity-matching to create pharmacologic and exercise groups with similar risk profiles.
Results
In comparison to exercise patients, pharmacologic patients had an increased risk-adjusted hazard ratio for ACM for each level of ischemia: increased by 3.8-fold (95%CI 3.5-4.1) among nonischemic patients, 2.5-fold (95%CI 2.0-3.2) among mildly ischemic patients, and 2.6-fold (95%CI 2.1-3.3) among moderate/severe ischemic patients. Similar findings were observed among a propensity-matched cohort of 10,113 exercise and 10,113 pharmacologic patients as well as in an additional cohort that also excluded patients with noncardiac co-morbidities.
Conclusions
Patients requiring pharmacologic stress testing manifest substantially heightened clinical risk at each level of myocardial ischemia and even when myocardial ischemia is absent. These findings suggest the need to study the pathophysiological drivers of increased risk in association with pharmacologic testing and to convey this risk in clinical reports.



J Nucl Cardiol: 11 Oct 2020; epub ahead of print

Feasibility of exercise treadmill N-ammonia positron emission tomography myocardial perfusion imaging using an off-site cyclotron.

Harland DR, Galazka PZ, Rasmussen J, Mahlum D, Falk J, Port SC
Background
Myocardial perfusion imaging with treadmill exercise nitrogen-13 (N)-ammonia positron emission tomography (PET) presents a logistical challenge. We investigated the feasibility of exercise treadmill (GXT) N-ammonia PET MPI using an off-site cyclotron for production of N-ammonia.
Methods
Thirty-three patients underwent GXT N-ammonia PET MPI over 23 months. N-ammonia doses were prepared at an off-site cyclotron. Patients underwent N-ammonia resting and N-ammonia GXT emission and transmission scans at our facility. Image quality, perfusion data, and clinical variables were evaluated.
Results
We analyzed 33 patients (7/26 female/male). Mean age was 63 ± 12 years and mean BMI was 33.7 ± 6.9. GXT PET was feasible in all patients. Image quality was good in 29 patients, adequate in 3, and severely compromised in 1 patient. Summed stress score was 4.5 ± 5.7. Resting and GXT left ventricular ejection fractions were 63.7 ± 10.9% and 66.3 ± 13.1%. TID ratio was 1.0 ± 0.1.
Conclusions
Treadmill exercise N-ammonia PET is feasible in a large medical center without access to an on-site cyclotron. This technique requires close coordination with an off-site cyclotron but expands the role of PET to patients for whom exercise is more appropriate than pharmacologic stress imaging.



J Nucl Cardiol: 17 Oct 2020; epub ahead of print

Quantitative clinical nuclear cardiology, part 2: Evolving/emerging applications.

Slomka PJ, Moody JB, Miller RJH, Renaud JM, Ficaro EP, Garcia EV

Quantitative analysis has been applied extensively to image processing and interpretation in nuclear cardiology to improve disease diagnosis and risk stratification. This is Part 2 of a two-part continuing medical education article, which will review the potential clinical role for emerging quantitative analysis tools. The article will describe advanced methods for quantifying dyssynchrony, ventricular function and perfusion, and hybrid imaging analysis. This article discusses evolving methods to measure myocardial blood flow with positron emission tomography and single-photon emission computed tomography. Novel quantitative assessments of myocardial viability, microcalcification and in patients with cardiac sarcoidosis and cardiac amyloidosis will also be described. Lastly, we will review the potential role for artificial intelligence to improve image analysis, disease diagnosis, and risk prediction. The potential clinical role for all these novel techniques will be highlighted as well as methods to optimize their implementation.



J Nucl Cardiol: 15 Oct 2020; epub ahead of print

Novel dietary protocol prior to 18F-fluorodeoxyglucose positron emission tomography to evaluate for cardiac sarcoidosis.

Hutt E, Jaber WA, Jellis C, Mountis MM, Cremer PC

The diagnosis of cardiac sarcoidosis (CS) is challenging. Recently, guidelines incorporated cardiac positron emission tomography (PET) with 18F-Fluorodeoxyglucose (F18-FDG) as a non-invasive diagnostic modality for the detection and follow-up of CS. However, this technique is dependent of patient dietary preparation to suppress physiological myocardial F18-FDG uptake. We present a case of possible CS which highlights a novel preparation protocol that facilitated appropriate myocardial suppression.



J Nucl Cardiol: 13 Oct 2020; epub ahead of print

Correction to: Performance of Tc-aprotinin scintigraphy for diagnosing light chain (AL) cardiac amyloidosis confirmed by endomyocardial biopsy.

Awaya T, Minamimoto R, Iwama K, Kubota S, ... Hiroe M, Moroi M

This prospective study was conducted according to the principles outlined within the Declaration of Helsinki, and approved by the Ethics Review Board of National Center for Global Health and Medicine (NCGM-G-00839-01, NCGM-G-00839-02).



J Nucl Cardiol: 30 Jul 2020; 27:1154

Cardiac uptake patterns in routine 18F-FDG PET-CT scans: A pictorial review.

Gupta K, Jadhav R, Prasad R, Virmani S

Broad variability of 18F-Fluoro-2-deoxyglucose (FDG) uptake is noted in myocardium while performing FDG PET-CT scans for viability, infection, or oncologic purposes. While most of the uptakes are considered non-specific, presence of underlying cardiac disease is seldom encountered. With this presentation, our intent is to pictorially highlight the variable FDG uptake patterns associated with the normal variations, benign, and malignant disease.



J Nucl Cardiol: 30 Jul 2020; 27:1296-1305

Could myocardial viability be related to left ventricular dyssynchrony? Simultaneous evaluation by gated SPECT-MPI.

Padrón K, Peix A, Cabrera L, Garcia J, ... Mena E, Fernandez Y
Background
Left ventricular contraction dyssynchrony (LVCD) has been related to induced ischemia and transmural scar but the interplay of myocardial viability and dyssynchrony is unknown. The aim of the present study was to establish the role of dyssynchrony in the context of a viability study performed with nitrate augmentation gated single photon emission computed tomography (GSPECT) myocardial perfusion imaging (MPI).
Methods
Fifty-four consecutive patients with ischemic dilated cardiomyopathy (IDC) and depressed left ventricular ejection fraction (LVEF) were included. They underwent a two-day rest/nitroglycerine (NTG) study GSPECT MPI to determine the myocardial viability. Patients with a nitrate-induced uptake increase of > 10% vs baseline, in at least, two consecutive dysfunctional segments were considered viable as well as those who showed no improvement in the uptake but the uptake was > 50% on post NTG study. Patients with no nitrate-induced uptake increase of > 10% and the uptake of < 50% were considered non-viable. Perfusion, function and LVCD were compared in 25 viable patients vs 29 non-viable patients at baseline and after NTG administration.
Results
After NTG administration, in the viable group, the LVEF increased (36.44 ± 6.64% vs 39.84 ± 6.39%) and the end-systolic volume decreased significantly (119.28 ± 31.77 mL vs 109.08 ± 33.17 mL) (P < 0.01). These patients also experienced a significant reduction in the LVCD variables: phase standard deviation was reduced in the post NTG study (57.77° ± 19.47° vs 52.02° ± 17.09°) as well as the phase histogram bandwidth (190.20° ± 78.83° vs 178.0° ± 76.14°) (P < 0.05). Functional and LVCD variables remained similar in the non-viable patients (P > 0.05).
Conclusion
In patients with IDC and depressed LVEF, the myocardial viability detected by rest/ NTG GSPECT MPI, might determine LVCD improvement.



J Nucl Cardiol: 30 Jul 2020; 27:1158-1167

Review of cardiovascular imaging in the Journal of Nuclear Cardiology 2019: Single-photon emission computed tomography.

Hage FG, AlJaroudi WA

In 2019, the Journal of Nuclear Cardiology published excellent articles pertaining to imaging in patients with cardiovascular disease. In this review, we will summarize a selection of these articles to provide a concise review of the main advancements that have recently occurred in the field and provide the reader with an opportunity to review a wide selection of articles. In the first article of this 2-part series, we focused on publications dealing with positron emission tomography, computed tomography, and magnetic resonance. This review will place emphasis on myocardial perfusion imaging using single-photon emission computed tomography summarizing advances in the field including in diagnosis and prognosis, non-perfusion variables, safety of testing, imaging in patients with heart failure and renal disease.



J Nucl Cardiol: 30 Jul 2020; 27:1171-1179

Quantitation of myocardial Tc-HMDP uptake with new SPECT/CT cadmium zinc telluride (CZT) camera in patients with transthyretin-related cardiac amyloidosis: Ready for clinical use?

Bellevre D, Bailliez A, Delelis F, Blaire T, ... Maréchaux S, Manrique A
Background
The aim of this study was to investigate the feasibility of assessing absolute myocardial 99mTc-HMDP uptake in patients with suspected cardiac ATTR using SUV with a whole-body CZT SPECT-CT camera (DNM670CZT).
Methods
Fifteen patients with suspected cardiac ATTR (Perugini ≥ 2) underwent a conventional 99mTc-HMDP planar imaging and a thoracic SPECT/CT using a DNM 670CZT. A control group consisted of 15 patients with negative scintigraphy (Perugini < 2). SUVmax (mg·L) and percentage of injected dose (%ID) were calculated in a cardiac volume of interest (VOI) encompassing the left ventricle. VOIs were also placed in the lung, the right pectoris major, and the sternum. A heart-to-lung SUVmax ratio (HLR) was calculated.
Results
All ATTR patients demonstrated an increased cardiac HMDP SUVmax (12.2 ± 3.7 mg·L) vs controls (3.5 ± 1.2, P < .0001). Percentage of ID, pectoral uptake and HLR were significantly higher in the ATTR group (1.1 ± 0.3 vs 0.15 ± 0.8, P < .0001; 1.5 ± 0.3 vs 0.9 ± 0.3, P < .0001; 9.7 ± 3 vs 4.3 ± 2.2, P < .0001). Bone uptake was not statistically different between the two groups.
Conclusion
This study demonstrated the feasibility of quantitative 99mTc-HMDP SUVmax measurement using a whole-body SPECT/CT CZT camera in patients with suspected cardiac ATTR.



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

Quantification of myocardial blood flow (MBF) and reserve (MFR) incorporated with a novel segmentation approach: Assessments of quantitative precision and the lower limit of normal MBF and MFR in patients.

Liu H, Thorn S, Wu J, Fazzone-Chettiar R, ... Sinusas AJ, Liu YH
Background
Quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) has shown diagnostic and prognostic values for the assessment of coronary artery disease (CAD). This study aimed to evaluate in patients a highly automatic Yale-MQ (myocardial blood flow quantification) software incorporated with a novel image segmentation approach for quantification of global and regional MBF and MFR from dynamic Rb cardiac positron emission tomography (PET).
Methods
Global and regional MBFs and MFRs were quantified in 80 patients (18 normal and 62 CAD subjects) by two different observers using the Yale-MQ software. Lower limits of normal (LLN) values and intra- and inter-observer variabilities of MBFs and MFRs were calculated for the assessment of quantitative precision. The Yale-MQ was compared with a commercially available software (Corridor 4DM) being used as a reference.
Results
The Yale-MQ method provided precise assessments of LLNs of MBF and MFR. The global and regional MBFs and MFR quantified via Yale-MQ were correlated strongly with those via Corridor4DM (R ≥ 0.867). The intra- and inter-observer variabilities of MBFs and MFRs quantified via Yale-MQ were small (≤ 7.7% for MBFs and ≤ 10.0% for MFRs) with excellent correlations (R ≥ 0.980 for MBFs and R ≥ 0.976 for MFRs).
Conclusions
The new Yale-MQ software associated with the automatic processing scheme provides a highly reproducible clinical tool for precise quantification of MBF and MFR in patients with reliable LLN values.



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

F-NaF PET uptake characteristics of coronary artery culprit lesions in a cohort of patients of acute coronary syndrome with ST-elevation myocardial infarction and chronic stable angina: A hybrid fluoride PET/CTCA study.

Ashwathanarayana AG, Singhal M, Satapathy S, Sood A, ... Krishnappa D, Rana N
Background
F-NaF PET/CT identifies high-risk plaques due to active calcification in coronary arteries with potential to characterize plaques in ST-elevation myocardial infarction (MI) and chronic stable angina (CSA) patients.
Methods
Twenty-four MI and 17 CSA patients were evaluated with F-NaF PET/CTCA for SUV and TBR values of culprit and non-culprit plaques in both groups (inter-group and intra-group comparison), and pre- and post-interventional MI plaques sub-analysis.
Results
Culprit plaques in MI patients had significantly higher SUV (1.6; IQR 0.6 vs 1.3; IQR 0.3, P = 0.03) and TBR (1.4; IQR 0.6 vs 1.1; IQR 0.4, P = 0.006) than culprit plaques of CSA. Pre-interventional culprit plaques of MI group (n = 11) revealed higher SUV (P = 0.007) and TBR (P = 0.008) values than culprit CSA plaques. Culprit plaques showed significantly higher SUV (P = 0.006) and TBR (P = 0.0003) than non-culprit plaques in MI group, but without significant difference between culprit and non-culprit plaques in CSA group. With median TBR cutoff value of 1.4 in MI culprit plaques, 6/7 plaques (85.7%) among the event prone non-culprit lesions had TBR values > 1.4 in CSA group.
Conclusion
The study shows higher SUV and TBR values in MI culprit plaques and comparable TBR values for event prone plaques of CSA group in identifying high-risk plaques.



J Nucl Cardiol: 26 Jul 2020; epub ahead of print

Optimal Tc activity ratio in the single-day stress-rest myocardial perfusion imaging protocol: A multi-SPECT phantom study.

Zoccarato O, Matheoud R, Lecchi M, Scabbio C, Claudio M, Brambilla M
Background
This investigation used image data generated by an anthropomorphic phantom to determine the minimal Tc rest-stress activity concentration ratio (R) able to minimize the ghosting effect in the single-day stress-first myocardial perfusion imaging, using different positions of the perfusion defect (PD), scanners and reconstruction protocols.
Methods
A cardiac phantom with a simulated PD was imaged under different R using different gamma cameras and reconstruction algorithms. The residual activity from precedent stress administration was simulated by modeling effective half-times in each compartment of the phantom and assuming a delay of 3 hours between the stress and rest studies. The net contrast (NC) of the PD in the rest study was assessed for different R, PD positions and scanner/software combinations. The optimal R will be the one that minimize the NC in the rest images Results: The activity concentration ratio R, the position of the PD and the scanner/software combinations were all main effects with a statistically significant impact on the NC, in decreasing order of relevance. The NC diminished significantly only for R values up to 2. No further improvement was observed for NC for R values above 2 and up to 3. NC was significantly higher in anteroseptal than in posterolateral positions of the PD and higher for solid-state cameras.
Conclusions
A rest-stress activity concentration ratio R of 2 in single-day stress-first myocardial perfusion imaging is enough to achieve the maximum net contrast in the PD. This ratio should be used to optimize patient\'s radiation exposure.



J Nucl Cardiol: 26 Jul 2020; epub ahead of print

Coexistent transthyretin amyloid cardiomyopathy and monoclonal gammopathy: Diagnostic challenges and prognostic implications.

Lee Chuy K, Gomez J, Malhotra S

Establishing an accurate diagnosis of amyloid subtype in patients with coexistent cardiac amyloidosis and monoclonal gammopathy is crucial due to treatment and prognostic implications. Here, we discuss a case of coexistent diagnoses of transthyretin amyloid cardiomyopathy and smoldering multiple myeloma, highlighting the challenges associated with the possibility of several disease combinations and the limitations of diagnostic testing. In addition, the importance of clinical clues such as disease course and progression, patient preference, and multidisciplinary collaboration should not be discounted in the diagnostic and management approach of these patients.



J Nucl Cardiol: 26 Jul 2020; epub ahead of print

F-FDG positron emission tomography/computed tomography of cardiac implantable electronic device infections.

Salomäki SP, Saraste A, Kemppainen J, Hurme S, ... Pirilä L, Hohenthal U
Background
The diagnosis of cardiac implantable electronic device (CIED) infection is challenging because of its variable presentations. We studied the value of 2-[F]fluoro-2-deoxy-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT) in the detection of CIED infection.
Methods and results
Thirty patients with suspected CIED infection underwent F-FDG-PET/CT. The control group was ten patients with asymptomatic CIED who underwent cancer-related F-FDG-PET/CT. F-FDG-PET/CT was evaluated visually, semiquantitatively as maximum standardized uptake value (SUV) and target-to-background ratio (TBR). Final diagnosis of CIED infection was based on clinical and bacteriological data. F-FDG-PET/CT was visually positive in all 9 patients with recent (≤ 8 weeks) implantation of CIED, but only 4 had confirmed CIED infection. F-FDG-PET/CT was true positive in 9 out of 21 cases with remote implantation of CIED and false positive in 3 (14.3%) cases. F-FDG-PET/CT was also false positive in 3 (30%) cases of control group. The SUV of the pocket area was significantly higher in patients with CIED infection than in the control group (4.8 ± 2.4 vs 2.0 ± .8, P < .001). By using the cut-off value of TBR ≥ 1.8, sensitivity of F-FDG-PET/CT for the diagnosis of CIED infection in patients with remote implantation was 90% and specificity 73%, PPV 75%, and NPV 89%.
Conclusions
F-FDG-PET/CT is a sensitive but nonspecific method in the diagnosis of CIED infection.



J Nucl Cardiol: 30 Jul 2020; epub ahead of print

Safety measures and clinical outcome of Nuclear Cardiology Department during Covid-19 lockdown pandemic: Northern Italy experience.

Scrima G, D\'Amico M, Bertuccio G, Canavese G, De Sanctis P
Background
The Covid-19 pandemic led to a complete renewal of clinical activities of Italian hospitals. During the lockdown, all hospitals in Italy had to suspend non-urgent clinical activities. The prolonged suspension of elective activities could have caused a series of problems.
Methods
A new ad hoc protocol was designed. Single-day fast-imaging protocol with regadenoson-stress 99mTc-tetrofosmin imaging was preferred. Patients were contacted by phone 4 days before the test and answered to a questionnaire which will be repeated on the day of the exam. Body temperature <37.5 degrees C and no Covid-19 symptoms were necessary to enter the unit. Patients wore surgical mask and gloves. Social distancing was maintained throughout the examination. Healthcare professionals wore a personal protective equipment.
Results
A total of 46 patients were studied from April 7 to May 15, 2020, before the publication of the recommendations from ASNC and SNMMI. None of the patients experienced complications. Follow-up of patients discharged was carried by phone. No Covid-19 infection symptoms were reported. On May 18, 2020 all the healthcare providers of nuclear cardiology department underwent serological testing IgG and IgM and none were positive.
Conclusion
Strict ad hoc hygiene protocol for Covid-19 pandemic avoids diagnostic-therapeutic delay and lengthening of waiting lists. Our experience confirms that pursuing WHO recommendations and recent indication of ASNC and SNMMI is safe for both health providers and patients. Moreover, the incidence of significant inducible ischemia rises when correct stratification of patients is performed.



J Nucl Cardiol: 30 Jul 2020; epub ahead of print

A preliminary study of relationship among the degree of internal carotid artery stenosis, wall shear stress on MR angiography and F-FDG uptake on PET/CT.

Takami Y, Norikane T, Yamamoto Y, Fujimoto K, ... Kawanishi M, Nishiyama Y
Background
This preliminary study was undertaken to evaluate relationship among the degree of internal carotid artery (ICA) stenosis, wall shear stress (WSS) by computational fluid dynamics (CFD) on magnetic resonance angiography (MRA) and F-FDG uptake of ICA on PET/CT.
Methods
A total of 40 carotid arteries in 20 patients with carotid atherosclerotic disease were examined with MRA and F-FDG PET/CT. Atherosclerotic risk factors were assessed in all patients. Degree of ICA stenosis was calculated according to NASCET method. CFD analysis was performed and maximum WSS (WSSmax) was measured. F-FDG uptake in ICA was quantified using maximum target-to-blood pool ratio (TBRmax).
Results
Atherosclerotic risk factors did not affect imaging findings. There were significant correlations between WSSmax and degree of ICA stenosis (ρ = .81, P < .001), WSSmax and TBRmax (ρ = .64, P < .001), and TBRmax and degree of ICA stenosis (ρ = .50, P = .001).
Conclusions
These preliminary results indicate that there may be significant correlations among the degree of ICA stenosis, WSSmax and TBRmax in patients with carotid artery stenosis.



J Nucl Cardiol: 01 Aug 2020; epub ahead of print

Radionuclide ventriculography phase analysis for risk stratification of patients undergoing cardiotoxic cancer therapy.

Jones KA, Small AD, Ray S, Hamilton DJ, ... Goodfield NER, Paterson CA
Background
Accurate diagnostic tools to identify patients at risk of cancer therapy-related cardiac dysfunction (CTRCD) are critical. For patients undergoing cardiotoxic cancer therapy, ejection fraction assessment using radionuclide ventriculography (RNVG) is commonly used for serial assessment of left ventricular (LV) function.
Methods
In this retrospective study, approximate entropy (ApEn), synchrony, entropy, and standard deviation from the phase histogram (phase SD) were investigated as potential early markers of LV dysfunction to predict CTRCD. These phase parameters were calculated from the baseline RNVG phase image for 177 breast cancer patients before commencing cardiotoxic therapy.
Results
Of the 177 patients, 11 had a decline in left ventricular ejection fraction (LVEF) of over 10% to an LVEF below 50% after treatment had commenced. This patient group had a significantly higher ApEn at baseline to those who maintained a normal LVEF throughout treatment. Of the parameters investigated, ApEn was superior for predicting the risk of CTRCD. Combining ApEn with the baseline LVEF further improved the discrimination between the groups.
Conclusions
The results suggest that RNVG phase analysis using approximate entropy may aid in the detection of sub-clinical LV contraction abnormalities, not detectable by baseline LVEF measurement, predicting a subsequent decline in LVEF.



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

Accuracy of F-FDG PET/CT in patients with the suspicion of cardiac implantable electronic device infections.

Jerónimo A, Olmos C, Vilacosta I, Ortega-Candil A, ... Ferrera C, Carreras JL
Background
Utility of F-FDG PET/CT in diagnosing infective endocarditis (IE) associated with cardiac implantable electronic devices (CIEDs) is not well established. Current ESC guidelines recommend the use of FDG-PET imaging in patients with CIEDs and positive blood cultures, but the number of studies evaluating the diagnostic performance of FDG-PET imaging in these patients remain limited. Our objective was to assess the diagnostic yield of F-FDG PET/CT in patients with suspected CIED infections, differentiating between pocket infection (PI) and lead infection (CIED-IE).
Methods and results
From 2013 to 2018, all patients (n = 63) admitted to a hospital with suspected CIED infection were prospectively recruited, undergoing a diagnostic work-up including a PET/CT. Explanted devices and material from the pocket were cultured. 14 cases corresponded to isolated PI and 13 were categorized as CIED-IE. Considering radionuclide uptake in the intracardiac portion of the lead, sensitivity and specificity of PET/CT for CIED-IE were 38.5% and 98.0%, respectively. Positive (19.2) and negative (0.6) likelihood ratio values, suggest that a positive PET/CT is much more probable to correspond to a patient with CIED-IE, whereas it is not possible to exclude this diagnosis when negative. For PI, sensitivity and specificity were 72.2% and 95.6%, respectively.
Conclusions
The yield of F-FDG PET/CT for suspected CIED infections differs depending on the site of infection. Due to very high specificity but poor sensitivity, negative studies must be interpreted with caution if the suspicion of CIED-IE is high.



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

Evolution of symptoms in patients with stable angina after normal regadenoson myocardial perfusion imaging: The Radionuclide Imaging and Symptomatic Evolution study (RISE).

McRee CW, Brice LR, Farag AA, Iskandrian AE, Hage FG
Background
Assessment of quality of life in patients with stable angina and normal gated single-photon emission computed tomography myocardial perfusion imaging (MPI) remains undefined. Symptom evolution in response to imaging findings has important implications on further diagnostic testing and therapeutic interventions.
Methods
Prospective cohort study was conducted at the University of Alabama at Birmingham enrolling 87 adult participants with stable chest pain from the emergency room, hospital setting, and outpatient clinics. Patients underwent MPI with technetium-99m Sestamibi and had a normal study. Participants filled out Seattle Angina Questionnaires initially and at 3-month follow-up.
Results
Among the 87 participants (60 ± 12 years; 40% African American, 70% women, 29% diabetes), the mean score increased by an absolute value of 14.2 [95% CI 10.4-18.7, P < .001] in physical limitation, 23.2 [95% CI 17.1-29.4, P < .001] in angina stability, 10.9 [95% CI 7.6-14.1, P < .001] in angina frequency, and 20.6 [95% CI 16.5-24.7, P < .001] in disease perception. There was no significant change in the mean score of treatment satisfaction [- 1.4, 95% CI - 4.7 to 1.8, P = .38]. At 3-month follow-up, 28 of 87 participants (32%) were angina free.
Conclusions
Patients with stable chest pain and normal MPI experience significant improvement in functional status, quality of life, and disease perception in the short term.



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

Functional significance of intermediate coronary stenosis in patients with single-vessel coronary artery disease: A comparison of dynamic SPECT coronary flow reserve with intracoronary pressure-derived fractional flow reserve (FFR).

Li C, Xu R, Yao K, Zhang J, ... Shi H, Ge J
Background
The aim of this study was to investigate the correlation of coronary flow reserve (CFR) assessed by rest/stress myocardial perfusion imaging with dynamic single-photon emission computed tomography (SPECT) with intracoronary pressure-derived fractional flow reserve (FFR) in patients with single-vessel coronary artery disease (CAD).
Methods
Patients with suspected or known stable CAD who were referred for invasive coronary angiography were prospectively enrolled. Both invasive FFR and SPECT were performed in subjects with single-vessel intermediate coronary stenosis. A cutoff value of < 0.8 was used to define abnormal FFR.
Results
A total of 34 patients were enrolled. The mean age of the subjects was 62.1 ± 6.7 years, and 79.4% were male. SPECT-derived CFR showed a significantly moderate correlation with FFR (r = 0.505, P = .003). The diagnostic performance for the identification of abnormal FFR in terms of sensitivity, specificity, and accuracy was 88.9%, 83.3%, and 87.9%, respectively, for CFR, with an optimized cutoff value of 1.73.
Conclusion
In patients with single-vessel CAD, SPECT CFR was useful for the detection of functionally significant stenosis. Our data support the use of this technique as an optional method for hemodynamic assessment, especially when FFR results are in normal range.



J Nucl Cardiol: 06 Aug 2020; epub ahead of print

Autonomic disorders and myocardial 123I-metaiodobenzylguanidine scintigraphy in Huntington\'s disease.

Assante R, Salvatore E, Nappi C, Peluso S, ... Pappatà S, De Rosa A
Background
Huntington\'s disease (HD) patients often present with abnormal modulation of blood pressure and heart rate. We investigated whether cardiac autonomic innervation assessed by 123I-metaiodobenzylguanidine (MIBG) imaging is impaired in HD patients, in comparison with controls (Ctrl).
Methods
Fifteen patients (6 F and 9 M) were assessed by the motor section of the Unified HD Rating Scale, the Total Function Capacity, and the scale for outcomes in Parkinson\'s disease-autonomic (SCOPA-AUT) questionnaire. All patients and 10 Ctrl (5 F and 5 M) underwent 123I-MIBG imaging. From planar images, the early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates (WR) were calculated.
Results
We did not find significant differences in early and late H/M ratios and WR between the two groups. At individual level, three patients showed reduced early and/or late H/M ratios. The most common autonomic complaints were gastrointestinal and genitourinary disorders. SCOPA-AUT questionnaire score results positively correlated with the disease duration and WR.
Conclusions
Our study indicates that myocardial postganglionic sympathetic innervation is essentially preserved or only minimally involved in HD. These findings suggest that the cardiovascular dysfunction might be mainly due to the impairment of brain areas associated with the regulation and modulation of the heart function.



J Nucl Cardiol: 15 Aug 2020; epub ahead of print

Coronary artery disease in patients with human immunodeficiency virus infection.

Mondal P, Aljizeeri A, Small G, Malhotra S, ... Al-Mallah MH, Jain D

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



J Nucl Cardiol: 19 Aug 2020; epub ahead of print

Prototype device for endoventricular beta-emitting radiotracer detection and molecularly-guided intervention.

Stendahl JC, Liu Z, Boutagy NE, Nataneli E, Daghighian F, Sinusas AJ
Background
We have set out to develop a catheter-based theranostic system that: (a) identifies diseased and at-risk myocardium via endocardial detection of systemically delivered β-emitting radiotracers and (b) utilizes molecular signals to guide delivery of therapeutics to appropriate tissue via direct intramyocardial injection.
Methods
Our prototype device consists of a miniature β-radiation detector contained within the tip of a flexible intravascular catheter. The catheter can be adapted to incorporate an injection port and retractable needle for therapeutic delivery. The performance of the β-detection catheter was assessed in vitro with various β-emitting radionuclides and ex vivo in hearts of pigs following systemic injection of F-fluorodeoxyglucose (F-FDG) at 1-week post-myocardial infarction. Regional catheter-based endocardial measurements of F activity were compared to regional tissue activity from PET/CT images and gamma counting.
Results
The β-detection catheter demonstrated sensitive in vitro detection of β-radiation from Na (β), F (β), and Tl (β), with minimal sensitivity to γ-radiation. For F, the catheter demonstrated a sensitivity of 4067 counts/s/μCi in contact and a spatial resolution of 1.1 mm FWHM. Ex vivo measurements of endocardial F activity with the β-detection catheter in the chronic pig infarct model demonstrated good qualitative and quantitative correlation with regional tissue activity from PET/CT images and gamma counting.
Conclusion
The prototype β-detection catheter demonstrates sensitive and selective detection of β and β emissions over a wide range of energies and enables high-fidelity ex vivo characterization of endocardial activity from systemically delivered F-FDG.



J Nucl Cardiol: 19 Aug 2020; epub ahead of print

Inter-observer reproducibility and intra-observer repeatability in Tc-pyrophosphate scan interpretation for diagnosis of transthyretin cardiac amyloidosis.

Singh V, Cuddy S, Kijewski MF, Park MA, ... Di Carli MF, Dorbala S
Aim
The purpose of this study was to determine the inter- and intra-observer variability in technetium-pyrophosphate (Tc-PYP) scan interpretation for diagnosis of transthyretin cardiac amyloidosis (ATTR).
Methods and results
Our study cohort comprised 100 consecutive subjects referred for Tc-PYP imaging based on clinical suspicion of ATTR cardiac amyloidosis. Myocardial Tc-PYP uptake was assessed by both visual (comparison of myocardial to rib uptake) and semi-quantitative (heart-to-contralateral lung uptake ratio, H:CL) methods. Twenty scans were analyzed twice, at least 48 hours apart, by each of two independent observers. Patients with visual scores of ≥ 2 on planar imaging as well as myocardial uptake on SPECT/CT were classified as ATTR positive. Diagnosis of ATTR by visual Tc-PYP grade was perfectly reproducible [concordance: positive and negative scans 100% (53/53 and 47/47, respectively). Both inter- and intra-observer correlations for H:CL ratio (r = 0.90, 0.99 (Observer 1) and 0.98 (Observer 2), respectively) and repeatability values on Bland-Altman plots were excellent. The coefficient of variation (%) for Observers 1 and 2 was 3.21 (2.14 to 4.29) and 7.49 (4.95 to 10.09), respectively. In addition, there was 100% concordance in positive and negative scan interpretation by visual grading between novice CV imagers (< 3 years\' experience) and an experienced CV imager (10 years\' experience).
Conclusions
This study showed excellent inter-observer reproducibility and intra-observer repeatability of Tc-PYP visual scan interpretation and H:CL ratio for diagnosis of cardiac ATTR amyloidosis. Cardiac ATTR amyloidosis can be diagnosed reliably using Tc-PYP SPECT/CT by novice and experienced CV imagers.



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

Prediction of appropriate ICD therapy in patients with ischemic heart failure.

Sazonova SI, Atabekov TA, Batalov RE, Mishkina AI, ... Zavadovsky KV, Popov SV
Background
Previous studies show inconsistent results on the role of innervation imaging (with I-123-mIBG) and perfusion imaging in predicting appropriate ICD therapy (aICDth). These studies included patients with both dilated and ischemic cardiomyopathy. This study compared the ability of I-mIBG imaging along with perfusion imaging (using thallium-199) to predict aICDth in patients with ischemic heart failure (IHF) in relation to indication for ICD implantation (primary vs. secondary prevention of sudden cardiac death (SCD)).
Methods
mIBG/thallium SPECT imaging were performed before ICD implantation in 80 patients with IHF: 49 candidates for primary and 31 for secondary SCD prevention.
Results
During a mean follow-up of 18 months, the imaging results could not predict patients with appropriate ICD therapy among patients with ICD implants for primary SCD prevention. While in the secondary SCD prevention group, those who received a ICDth had significantly larger summed scores of regional perfusion and innervation impairment, but not higher heart-to-mediastinal mIBG ratio. The best results to predict aICDth were using mIBG summed score (cut-off point > 34%, sensitivity 72%, specificity 100%, AUC 0.909, P < 0.0001).
Conclusion
The prognostic value of innervation and perfusion imaging in patients with IHF differ based on indication for ICD implantation (primary vs. secondary prevention of SCD).



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

Myocardial ischemia and previous infarction contribute to left ventricular dyssynchrony in patients with coronary artery disease.

Hämäläinen H, Corovai A, Laitinen J, Laitinen TM, ... Kivelä A, Laitinen TP
Aims
The aim of this study was to characterize determinants of left ventricular mechanical dyssynchrony (LVMD) in patients with coronary artery disease (CAD).
Methods
Medical records and results of myocardial perfusion SPECT/CT studies were evaluated in 326 patients with previously diagnosed CAD. LVMD was assessed with the phase analysis of ECG-gated myocardial SPECT. Dyssynchrony was described with phase histogram bandwidth (PHBW), standard deviation (PHSD) or entropy (PHE) values above limit of the highest normal.
Results
Prevalence of LVMD was 29% in CAD patients. Size of the infarction scar and ischemia extent correlated significantly with PHBW, PHSD and PHE (P < 0.001 for all). Independent predictors of LVMD were myocardial infarction scar (P = 0.004), ischemia extent (P = 0.003), and QRS duration (P = 0.003). Previous percutaneous coronary intervention and coronary artery bypass grafting did not independently predict dyssynchrony.
Conclusions
Almost one-third of CAD patients had significant LVMD. Dyssynchrony was associated with earlier myocardial infarction and presence of myocardial ischemia. Previous percutaneous coronary intervention and coronary artery bypass grafting did not independently predict dyssynchrony.



J Nucl Cardiol: 30 Aug 2020; epub ahead of print

Comparison of planar with tomographic pyrophosphate scintigraphy for transthyretin cardiac amyloidosis: Perils and pitfalls.

Asif T, Gomez J, Singh V, Doukky R, Nedeltcheva A, Malhotra S
Background
Tc-99m pyrophosphate (PYP) SPECT is recommended for indeterminate findings on planar imaging. We aimed to compare the findings on planar PYP scintigraphy alone to that of routinely performed PYP SPECT.
Methods
PYP scintigraphy data of 133 patients (53% men; mean age 76 years) were evaluated. SPECT was routinely performed following 1-hour planar imaging, in all cases. Semiquantitative visual score and heart-to-contralateral (H/CL) ratio were determined in all patients as recommended.
Results
PYP images from 35 patients (26%) were considered to be positive based on SPECT myocardial uptake. Among them, 20 (57%) had a H/CL ratio ≥1.5 and 34 had a visual score ≥ 2. SPECT identified myocardial uptake in one patient with a visual score < 2 and refuted the presence of myocardial uptake in two patients with a visual score ≥ 2. Visual score correlated well with SPECT (r = 0.94; P < .0001) and had an accuracy of 98% for tomographic myocardial uptake. Addition of H/CL ratio reduced the diagnostic performance of visual score.
Conclusions
Planar-derived visual score has an excellent accuracy for tomographic myocardial uptake, though it misclassifies a small proportion of patients. H/CL ratio decreases the diagnostic certainty of planar imaging. Tomographic imaging prevents misdiagnoses and should always be performed.



J Nucl Cardiol: 07 Sep 2020; epub ahead of print

Development, diagnostic performance, and interobserver agreement of a F-flurpiridaz PET automated perfusion quantitation system.

Packard RRS, Cooke CD, Van Train KF, Votaw JR, ... Garcia EV, Maddahi J
Background
Computerized methodologies standardize the myocardial perfusion imaging (MPI) interpretation process.
Methods
To develop an automated relative perfusion quantitation approach for F-flurpiridaz, PET MPI studies from all phase III trial participants of F-flurpiridaz were divided into 3 groups. Count distributions were obtained in N = 40 normal patients undergoing pharmacological or exercise stress. Then, N = 90 additional studies were selected in a derivation group. Following receiver operating characteristic curve analysis, various standard deviations below the mean normal were used as cutoffs for significant CAD, and interobserver variability determined. Finally, diagnostic performance was compared between blinded visual readers and blinded derivations of automated relative quantitation in the remaining N = 548 validation patients.
Results
Both approaches yielded comparable accuracies for the detection of global CAD, reaching 71% and 72% by visual reads, and 72% and 68% by automated relative quantitation, when using CAD ≥ 70% or ≥ 50% stenosis for significance, respectively. Similar results were observed when analyzing individual coronary territories. In both pharmacological and exercise stress, automated relative quantitation demonstrated significantly more interobserver agreement than visual reads.
Conclusions
Our automated method of F-flurpiridaz relative perfusion analysis provides a quantitative, objective, and highly reproducible assessment of PET MPI in normal and CAD subjects undergoing either pharmacological or exercise stress.



J Nucl Cardiol: 06 Sep 2020; epub ahead of print

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: 05 Sep 2020; epub ahead of print

Prognostic value of ventricular mechanical dyssynchrony in patients with left ventricular aneurysm: A comparative study of medical and surgical treatment.

Lu X, Zhao M, Tian C, Wei H, ... Zhang X, Li X
Background
The prognostic value of left ventricular (LV) mechanical dyssynchrony (MD) in patients with LV aneurysm (LVA) is unclear. This study aimed to investigate the long-term prognostic value of LVMD in LVA patients.
Methods
92 consecutive patients who underwent Tc-sestamibi-gated SPECT myocardial perfusion imaging (GSPECT) were retrospectively analyzed and followed-up for a median of 63 months (range, 1-73 months). LV function and histogram bandwidth (BW) were analyzed by QGS software. LVMD was defined by ROC analysis. Cardiac death was defined as the primary endpoint, and the composite of cardiac deaths and severe or acute heart failure (MACE) as the secondary endpoint.
Results
The annual cardiac mortality rate of LVA patients with LVMD and treated by surgical therapy was significantly lower than those treated by medical therapy (2.40% vs. 6.40%, P < .05) but not annual MACE rate (6.61% vs. 10.06%, P > .05). In patients without LVMD, no significant difference in survival and MACE-free survival between medical and surgical treatment. In addition, the occurrence of LVMD is related to the worsen cardiac outcome in terms of MACE and cardiac death, independent of the treatment methods. BW was an independent predictor for MACE (HR 1.010, P < .01) and LVEF (HR .928, P < .05) was an independent predictor for cardiac death in all LVA patients.
Conclusions
LVA patients with LVMD might be associated with high risk for cardiac death and surgical treatment might improve cardiac survival compared to medical therapy in these patients.



J Nucl Cardiol: 08 Sep 2020; epub ahead of print

First-in-human imaging and kinetic analysis of vesicular acetylcholine transporter density in the heart using [F]FEOBV PET.

Saint-Georges Z, Zayed VK, Dinelle K, Cassidy C, ... deKemp R, Tuominen L

In contrast to cardiac sympathetic activity which can be assessed with established PET tracers, there are currently no suitable radioligands to measure cardiac parasympathetic (cholinergic) activity. A radioligand able to measure cardiac cholinergic activity would be an invaluable clinical and research tool since cholinergic dysfunction has been associated with a wide array of pathologies (e.g., chronic heart failure, myocardial infarction, arrythmias). [F]Fluoroethoxybenzovesamicol (FEOBV) is a cholinergic radiotracer that has been extensively validated in the brain. Whether FEOBV PET can be used to assess cholinergic activity in the heart is not known. Hence, this study aimed to evaluate the properties of FEOBV for cardiac PET imaging and cholinergic activity mapping. PET data were collected for 40 minutes after injection of 230 ± 50 MBq of FEOBV in four healthy participants (1 female; Age: 37 ± 10; BMI: 25 ± 2). Dynamic LV time activity curves were fitted with Logan graphical, 1-tissue compartment, and 2-tissue compartment models, yielding similar distribution volume estimates for each participant. Our initial data show that FEOBV PET has favorable tracer kinetics for quantification of cholinergic activity and is a promising new method for assessing parasympathetic function in the heart.



J Nucl Cardiol: 08 Sep 2020; epub ahead of print

Prognostic utility of longitudinal quantification of PET myocardial blood flow early post heart transplantation.

Wiefels C, Almufleh A, Yao J, deKemp RA, ... Beanlands RS, Chih S
Background
Myocardial blood flow (MBF) quantification by Rubidium-82 positron emission tomography (PET) has shown promise for cardiac allograft vasculopathy (CAV) surveillance and risk stratification post heart transplantation. The objective was to determine the prognostic value of serial PET performed early post transplantation.
Methods and result
Heart transplant (HT) recipients at the University of Ottawa Heart Institute with 2 PET examinations (PET1 = baseline, PET2 = follow-up) within 6 years of transplant were included in the study. Evaluation of PET flow quantification included stress MBF, coronary vascular resistance (CVR), and myocardial flow reserve (MFR). The primary composite outcome was all-cause death, re-transplant, myocardial infarction, revascularization, allograft dysfunction, cardiac allograft vasculopathy (CAV), or heart failure hospitalization. A total of 121 patients were evaluated (79% male, mean age 56 ± 11 years) with consecutive scans performed at mean 1.4 ± 0.7 and 2.6 ± 1.0 years post HT for PET1 and PET2, respectively. Over a mean follow-up of 3.0 (IQR 1.8, 4.6) years, 26 (22%) patients developed the primary outcome: 1 death, 11 new or progressive angiographic CAV, 2 percutaneous coronary interventions, 12 allograft dysfunction. Unadjusted Cox analysis showed a significant reduction in event-free survival in patients with PET1 stress MBF < 2.1 (HR: 2.43, 95% CI 1.11-5.29 P = 0.047) and persistent abnormal PET1 to PET2 CVR > 76 (HR: 2.19, 95% CI 0.87-5.51 P = 0.045). There was no association between MFR and outcomes.
Conclusion
Low-stress MBF and persistent increased CVR on serial PET imaging early post HT are associated with adverse cardiovascular outcomes. Early post-transplant and longitudinal assessment by PET may identify at-risk patients for increased surveillance post HT.



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

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

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



J Nucl Cardiol: 19 Oct 2020; epub ahead of print

Reproducibility of global LV function and dyssynchrony parameters derived from phase analysis of gated myocardial perfusion SPECT: A multicenter comparison with core laboratory setting.

de Amorim Fernandes F, Peix A, Giubbini R, Karthikeyan G, ... Mesquita CT, Garcia EV
Background
Gated myocardial perfusion scintigraphy (GMPS) phase analysis is an important tool to investigate the physiology of left ventricular (LV) dyssynchrony. We aimed to test the performance of GMPS LV function and phase analysis in different clinical settings and on a diverse population.
Methods
This is a post hoc analysis of a prospective, non-randomized, multinational, multicenter cohort study. Clinical evaluation and GMPS prior to cardiac resynchronization therapy (CRT)(baseline) and 6-month post CRT (follow-up) were done. LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), LV ejection fraction (LVEF), LV phase standard deviation (LVPSD), and percentage of left ventricle non-viable (PLVNV) were obtained by 10 centers and compared to the core lab.
Results
276 GMPS studies had all data available from individual sites and from core lab. There were no statistically significant differences between all variables except for LVPSD. When subjects with no mechanical dyssynchrony were excluded, LVPSD difference became non-significant. LVESV, LVEF, LVPSD and PLVNV had strong correlation in site against core lab comparison. Bland-Altman plots demonstrated good agreement.
Conclusions
The presented correlation and agreement of LV function and dyssynchrony analysis over different sites with a diverse sample corroborate the strength of GMPS in the management of heart failure in clinical practice.



J Nucl Cardiol: 19 Oct 2020; epub ahead of print

Prognostic value of left ventricular mechanical dyssynchrony induced by exercise stress in patients with normal myocardial perfusion single-photon emission computed tomography.

Sakatani T, Kasahara T, Irie D, Tsubakimoto Y, ... Fujita H, Inoue K
Background
Left ventricular mechanical dyssynchrony (LVMD) induced by exercise stress was reported to be clinically useful in detecting multivessel coronary artery diseases. The aim of this study was to compare the prognostic value of LVMD induced by pharmacological stress with that induced by exercise stress.
Methods
We retrospectively examined 918 consecutive patients who underwent exercise (N = 310) or pharmacological stress (N = 608) Tc-tetrofosmin single-photon emission computed tomography (SPECT) with normal myocardial perfusion. LVMD was evaluated by phase analysis as the indices of phase bandwidth and phase standard deviation (PSD).
Results
During the follow-up period (2.2 ± 1.9 years), 74 major cardiac events (MCEs) occurred (7 cases of cardiac death, 17 cases of heart failure, and 50 cases of coronary intervention). In global patients, the indices of LVMD on rest images were significantly greater in patients with MCEs (bandwidth (°): 51 ± 31 vs 37 ± 21, P = .001, PSD: 14 ± 9 vs 10 ± 6, P = .001). The exercise stress bandwidth was significantly higher in patients with MCEs (62 ± 37° vs 42 ± 21°, P = .026), as was the pharmacological stress bandwidth (57 ± 35° vs 43 ± 24°, P = .006). Multivariate analysis demonstrated the exercise stress bandwidth to be an independent predictor of MCEs (HR 1.017, CI 1.003 to 1.032, P = .019), but the pharmacological stress bandwidth had no influence on MCEs.
Conclusions
LVMD induced by exercise stress was an independent predictor of MCEs in patients with normal perfusion SPECT, whereas that induced by pharmacological stress had no association with further events.



J Nucl Cardiol: 19 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

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