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

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

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 16 Sep 2021; epub ahead of print

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

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

© 2021. American Society of Nuclear Cardiology.

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

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

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

© 2021. The Author(s).

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

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

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

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 08 Sep 2021; epub ahead of print

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

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

© 2021. The Author(s).

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

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

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

© 2021. The Author(s).

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

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

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

© 2021. American Society of Nuclear Cardiology.

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

Multimodality imaging to distinguish between benign and malignant cardiac masses.

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

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 01 Sep 2021; epub ahead of print

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

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

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 01 Sep 2021; epub ahead of print

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

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

© 2021. American Society of Nuclear Cardiology.

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

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

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

© 2021. The Author(s).

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

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

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

© 2021. American Society of Nuclear Cardiology.

J Nucl Cardiol: 22 Aug 2021; epub ahead of print