Positron Emission Tomography Myocardial Perfusion Imaging Research Articles

Guiding early revascularization using [15O]H2O PET myocardial perfusion imaging - Impact of atrial fibrillation.

Myocardial perfusion imaging (MPI) using [15O]H2O positron emission tomography (PET) is used to guide the selection of patients with angina for invasive angiography and possible revascularization. Our study evaluated whether atrial fibrillation (AF): 1) reduces global hyperemic myocardial blood flow (MBF) and 2) whether [15O]H2O PET MPI effectively guides revascularization procedures for patients with ongoing AF. We prospectively recruited 346 patients with angina and persistent or paroxysmal AF referred for baseline/hyperemic [15O]H2O PET MPI. The primary outcome was revascularization within 3 months of MPI. In the analyses, patients were divided into four groups based on whether they had ongoing AF or sinus rhythm (SR) and whether they had previously documented coronary artery disease (CAD) or not. Thus, four groups were compared: SR-noCAD, AF-noCAD, SR-CAD and AF-CAD. Hyperemic MBF was affected by both ongoing AF and prior CAD [MBF (mL/min/g): 2.82 (SR-noCAD) vs. 2.12 (AF-noCAD) vs. 2.22 (SR-CAD) vs. 1.80 (AF-CAD), two-way ANOVA p<0.0001]. In multiple linear regression ongoing AF was independently associated with reduced hyperemic MBF. Every 0.1 mL/min/g decrease in hyperemic MBF was associated with a 23% increase in odds of early revascularization. ROC-analysis of vessel specific hyperemic MBF to predict early revascularization yielded the following areas under the ROC curve (AUC): SR-noCAD: 0.95 (p<0.0001); AF-noCAD: 0.79 (p<0.0001); SR-CAD: 0.78 (p<0.0001); AF-CAD: 0.88 (p<0.0001). Ongoing AF is associated with 19-25 % reduced global hyperemic MBF as measured by [15O]H2O MPI PET. Regardless, vessel specific hyperemic MBF still predicts early revascularization in patients with AF.

Phase I, first-in-human study of XTR004, a novel 18F-labeled tracer for myocardial perfusion PET: Biodistribution, radiation dosimetry, pharmacokinetics, and safety after a single injection at rest

ObjectivesThis study assessed the imaging characteristics, pharmacokinetics and safety of XTR004, a novel 18F-labeled Positron Emission Tomography (PET) myocardial perfusion imaging tracer, after a single injection at rest in humans. MethodsEleven healthy subjects (eight men and three women) received intravenous XTR004 (239–290 megabecquerel [MBq]). Safety profiles were monitored on the dosing day and three follow-up visits. Multiple whole-body PET scans were conducted over 4.7 h to evaluate biodistribution and radiation dosimetry. Blood and urine samples collected for 7.25 h were metabolically corrected to characterize pharmacokinetics. ResultsIn the first 0–12 min PET images of ten subjects, liver (26.81 ± 4.01), kidney (11.43 ± 2.49), lung (6.75 ± 1.76), myocardium (4.72 ± 0.67) and spleen (3.1 ± 0.84) exhibited the highest percentage of the injected dose (%ID). Myocardial uptake of XTR004 in the myocardium initially reached 4.72 %ID and 7.06 g/mL, and negligibly changed within an hour (Δ: 7.20%, 5.95%). The metabolically corrected plasma peaked at 2.5 min (0.0013896 %ID/g) and halved at 45.2 min. Whole-body effective dose was 0.0165 millisievert (mSv)/MBq. Cumulative urine excretion was 8.18%. Treatment-related adverse events occurred in seven out of eleven subjects (63.6%), but no severe adverse event was reported. ConclusionsXTR004 demonstrated a favorable safety profile, rapid, high, and stable myocardial uptake and excellent potential for PET myocardial perfusion imaging (MPI). Further exploration of XTR004 PET MPI for detecting myocardial ischemia is warranted.

Abstract 15719: Prognostic Interplay Between Myocardial Flow Reserve and Left Ventricular Ejection Fraction

Introduction: Myocardial flow reserve (MFR), measured using positron emission tomography (PET), has been shown to add incremental prognostic value in multiple patient populations. Whether this association is modified by left ventricular ejection fraction (LVEF) is not well studied. The aim of this analysis is to determine whether there is a prognostic interplay between myocardial flow reserve and LVEF. Methods: The study population included patients who had clinically indicated PET myocardial perfusion imaging and were prospectively followed for incident events. MFR was calculated as the ratio of stress to rest myocardial blood flow (MBF) (ml/min/g). Rest LVEF was calculated from end systolic and end diastolic LV volumes on gated images. Cox proportional hazards were used to study the association between MFR (&lt;2 vs ≥2) and incident cardiovascular events stratified by LVEF (&lt;50% vs ≥50%). Results: The study population included 5,523 patients (mean±SD age 67±12 years, 53% male), 16% of LVEF&lt;50% and 47% MFR &lt;2. Rest MBF was similar among patients with normal or reduced LVEF while stress MFR was lower with lower EF. In adjusted analysis, patients with impaired MFR had a higher incident event rate regardless of LVEF (Figure 1). Patients with MFR&lt;2 had a higher risk of incident outcomes in both LVEF ≥50% (HR=2.58, 95% CI:1.93 - 3.46, p&lt;0.001) and LVEF &lt;50% (HR=2.76, 95% CI: 1.62 - 4.70, p&lt;0.001); p-value for interaction= 0.045. Conclusions: Impaired MFR is associated with a higher risk of cardiovascular outcomes and death in patients with high or low LVEF.

Abstract 17801: Age-Specific Normal Values for Myocardial Blood Flow on 82rb Positron Emission Tomography

Introduction: Positron emission tomography (PET) myocardial perfusion imaging (MPI) is utilized to evaluate ischemia along with myocardial blood flow (MBF). The ability to adequately augment blood flow, measured by myocardial blood flow reserve (MBFR), is a measure of overall health of the coronary circulation and associated with lower major adverse cardiovascular events (MACE) and all-cause mortality. The age-specific ranges of MBFR in patients without demonstrable coronary artery disease (CAD) has not been well established. Hypothesis/Aim: To determine the effect of age on MBF and MBFR in a cohort of patients without demonstrable CAD. Methods: Patients who underwent PET MPI studies from 2012-2022 on Siemens PET/CT cameras were included if Summed Stress Score=0, coronary calcium score=0, and left ventricular ejection fraction ≥50%. Those with prior history of MI or coronary intervention, heart/kidney/liver transplant, cirrhosis, or CKD stage IV+ were excluded. MBF was calculated using a net retention model (ImagenQ, Cardiovascular Imaging Technologies, Kansas City, MO) and multivariable linear regression models were developed to predict MBF. Results: Among 3,235 patients (age 59.5+/-12.6 years, 24.2% male) with median rest MBF 0.74 [0.61-0.92] and stress MBF 1.71 [1.41-2.10], MBFR was 2.28 [1.93-2.72]. With increasing age, rest MBF remained fairly stable while stress MBF and MBFR decreased, such that for every 10 years of age, stress MBF decreased by 0.07 [95% CI 0.05-0.08] mL/min/g and MBFR decreased by 0.12 [95% CI 0.11-0.14] after multivariable adjustment. Age-specific predicted MBFR values are documented in the Table. Conclusions: In patients without demonstrable CAD, the MBFR decreases with age. Abnormal MBFR values under 2.0 may be seen in a significant number of older patients.

Reproducibility of Left Ventricular Function Derived From Cardiac Magnetic Resonance and Gated 13N-Ammonia Positron Emission Tomography Myocardial Perfusion Imaging: A Head-to-Head Comparison Using Hybrid Positron Emission Tomography/Magnetic Resonance

Cardiac magnetic resonance (CMR) and gated 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) offer accurate and highly comparable global left ventricular ejection fraction (LVEF) measurements. In addition to accuracy, however, reproducibility is crucial to avoid variations in LVEF assessment potentially negatively impacting treatment decisions. We performed a head-to-head comparison of the reproducibility of LVEF measurements derived from simultaneously acquired CMR and PET-MPI using different state-of-the-art commercially available software. 93 patients undergoing hybrid PET/MR were retrospectively included. LVEF was derived from CMR and PET-MPI at two separate core labs, using two state-of-the-art software packages for CMR (cvi42 and Medis Suite MR) and PET (QPET and CardIQ Physio). Intra- and inter-reader agreement was assessed using correlation and Bland-Altman (BA) analyses. While intra- and inter-reader reproducibility of LVEF was high among both modalities and all software packages (r≥0.87 and ICC≥0.91, all significant at p<0.0001), LVEF derived from PET-MPI and analyzed with QPET outperformed all other analyses (intra-reader reproducibility: r=0.99, ICC=0.99; inter-reader reproducibility: r=0.98, ICC=1.00; Pearson correlations significantly higher than all others at p≤0.0001). BA analyses showed smaller biases for LVEF derived from PET-MPI (-0.1% and +0.9% for intra-reader, -0.4% and -0.8% for inter-reader agreement) than those derived from CMR (+0.7% and +2.8% for intra-reader, -0.9% and -2.2% for inter-reader agreement) with similar results for BA limits of agreement. Gated 13N-ammonia PET-MPI provides equivalent reproducibility of LVEF compared to CMR. It may offer a valid alternative to CMR for patients requiring LV functional assessment.

Flurpiridaz F-18 PET Myocardial Perfusion Imaging in Patients With Suspected Coronary Artery Disease

BackgroundFlurpiridaz F-18 (flurpiridaz) is a novel positron emission tomography (PET) myocardial perfusion imaging tracer. ObjectivesThe purpose of this study was to further assess the diagnostic efficacy and safety of flurpiridaz for the detection and evaluation of coronary artery disease (CAD) defined as ≥50% stenosis by quantitative invasive coronary angiography (ICA). MethodsIn this second phase 3 prospective multicenter clinical study, 730 patients with suspected CAD from 48 clinical sites in the United States, Canada, and Europe were enrolled. Patients underwent 1-day rest/stress flurpiridaz PET and 1- or 2-day rest-stress Tc-99m–labeled single photon emission computed tomography (SPECT) before ICA. PET and SPECT images were read by 3 experts blinded to clinical and ICA data. ResultsA total of 578 patients (age 63.7 ± 9.5 years) were evaluable; 32.5% were women, 52.3% had body mass index ≥30 kg/m2, and 33.6% had diabetes. Flurpiridaz PET met the efficacy endpoints of the study; its sensitivity and specificity were significantly higher than the prespecified threshold value by 2 of the 3 readers. The sensitivity of flurpiridaz PET was higher than SPECT (80.3% vs 68.7%; P = 0.0003) and its specificity was noninferior to SPECT (63.8% vs 61.7%; P = 0.0004). PET area under the receiver-operating characteristic curves were higher than SPECT in the overall population (0.80 vs 0.68; P < 0.001), women, and obese patients (P < 0.001 for both). Flurpiridaz PET was superior to SPECT (P < 0.001) for perfusion defect size/severity evaluation, image quality, diagnostic certainty, and radiation exposure. Flurpiridaz PET was safe and well tolerated. ConclusionsThis second flurpiridaz PET myocardial perfusion imaging trial shows that flurpiridaz has utility as a new tracer for CAD detection, specifically in women and obese patients. (An International Study to Evaluate Diagnostic Efficacy of Flurpiridaz [18F] Injection PET MPI in the Detection of Coronary Artery Disease [CAD]; NCT03354273)

Incremental prognostic value of downstream positron emission tomography perfusion imaging after coronary computed tomography angiography: a study using machine learning.

To evaluate the incremental value of positron emission tomography (PET) myocardial perfusion imaging (MPI) over coronary computed tomography angiography (CCTA) in predicting short- and long-term outcome using machine learning (ML) approaches. A total of 2411 patients with clinically suspected coronary artery disease (CAD) underwent CCTA, out of whom 891 patients were admitted to downstream PET MPI for haemodynamic evaluation of obstructive coronary stenosis. Two sets of Extreme Gradient Boosting (XGBoost) ML models were trained, one with all the clinical and imaging variables (including PET) and the other with only clinical and CCTA-based variables. Difference in the performance of the two sets was analysed by means of area under the receiver operating characteristic curve (AUC). After the removal of incomplete data entries, 2284 patients remained for further analysis. During the 8-year follow-up, 210 adverse events occurred including 59 myocardial infarctions, 35 unstable angina pectoris, and 116 deaths. The PET MPI data improved the outcome prediction over CCTA during the first 4 years of the observation time and the highest AUC was at the observation time of Year 1 (0.82, 95% confidence interval 0.804-0.827). After that, there was no significant incremental prognostic value by PET MPI. PET MPI variables improve the prediction of adverse events beyond CCTA imaging alone for the first 4 years of follow-up. This illustrates the complementary nature of anatomic and functional information in predicting the outcome of patients with suspected CAD.

Incremental prognostic value of stress phase entropy over standard PET myocardial perfusion imaging variables.

Phase analysis can assess left ventricular dyssynchrony. The independent prognostic value of phase variables over positron emission tomography myocardial perfusion imaging (PET-MPI) variables including myocardial flow reserve (MFR) has not been studied. The aim of this study was to explore the prognostic value of phase variables for predicting mortality over standard PET-MPI variables. Consecutive patients who underwent pharmacological stress-rest 82Rb PET study were enrolled. All PET-MPI variables including phase variables (phase entropy, phase bandwidth, and phase standard deviation) were automatically obtained by QPET software (Cedars-Sinai, Los Angeles, CA). Cox proportional hazard analyses were used to assess associations with all-cause mortality (ACM). In a total of 3963 patients (median age 71years; 57% male), 923 patients (23%) died during a median follow-up of 5years. Annualized mortality rates increased with stress phase entropy, with a 4.6-fold difference between the lowest and highest decile groups of entropy (2.6 vs. 12.0%/year). Abnormal stress phase entropy (optimal cutoff value, 43.8%) stratified ACM risk in patients with normal and impaired MFR (both p < 0.001). Among three phase variables, only stress phase entropy was significantly associated with ACM after the adjustment of standard clinical and PET-MPI variables including MFR and stress-rest change of phase variables, whether modeled as binary variables (adjusted hazard ratio, 1.44 for abnormal entropy [> 43.8%]; 95%CI, 1.18-1.75; p < 0.001) or continuous variables (adjusted hazard ratio, 1.05 per 5% increase; 95%CI, 1.01-1.10; p = 0.030). The addition of stress phase entropy to the standard PET-MPI variables significantly improved the discriminatory power for ACM prediction (p < 0.001), but the other phase variables did not (p > 0.1). Stress phase entropy is independently and incrementally associated with ACM beyond standard PET-MPI variables including MFR. Phase entropy can be obtained automatically and included in clinical reporting of PET-MPI studies to improve patient risk prediction.

Long-term impact of myocardial inflammation on quantitative myocardial perfusion—a descriptive PET/MR myocarditis study

PurposeWhether myocardial inflammation causes long-term sequelae potentially affecting myocardial blood flow (MBF) is unknown. We aimed to assess the effect of myocardial inflammation on quantitative MBF parameters, as assessed by 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) late after myocarditis.MethodsFifty patients with a history of myocarditis underwent cardiac magnetic resonance (CMR) imaging at diagnosis and PET/MR imaging at follow-up at least 6 months later. Segmental MBF, myocardial flow reserve (MFR), and 13N-ammonia washout were obtained from PET, and segments with reduced 13N-ammonia retention, resembling scar, were recorded. Based on CMR, segments were classified as remote (n = 469), healed (inflammation at baseline but no late gadolinium enhancement [LGE] at follow-up, n = 118), and scarred (LGE at follow-up, n = 72). Additionally, apparently healed segments but with scar at PET were classified as PET discordant (n = 18).ResultsCompared to remote segments, healed segments showed higher stress MBF (2.71 mL*min−1*g−1 [IQR 2.18–3.08] vs. 2.20 mL*min−1*g−1 [1.75–2.68], p < 0.0001), MFR (3.78 [2.83–4.79] vs. 3.36 [2.60–4.03], p < 0.0001), and washout (rest 0.24/min [0.18–0.31] and stress 0.53/min [0.40–0.67] vs. 0.22/min [0.16–0.27] and 0.46/min [0.32–0.63], p = 0.010 and p = 0.021, respectively). While PET discordant segments did not differ from healed segments regarding MBF and MFR, washout was higher by ~ 30% (p < 0.014). Finally, 10 (20%) patients were diagnosed by PET-MPI as presenting with a myocardial scar but without a corresponding LGE.ConclusionIn patients with a history of myocarditis, quantitative measurements of myocardial perfusion as obtained from PET-MPI remain altered in areas initially affected by inflammation.Graphical abstractCMR = cardiac magnetic resonance; PET = positron emission tomography; LGE = late gadolinium enhancement

The incremental value of PET perfusion imaging over coronary CT angiography in predicting outcome. A study using machine learning

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Academy of Finland, Turku University Hospital Background Coronary computed tomography angiography (CTA) and myocardial perfusion imaging (MPI) are powerful non-invasive tools to evaluate the patients with suspected coronary artery disease (CAD). Purpose The goal of this study was to evaluate the incremental value of these imaging methods in predicting short- and long-term cardiac events using machine learning (ML) approaches. Methods 2411 patients with clinically suspected CAD underwent coronary CTA and subsequent positron emission tomography (PET) MPI. Following our local routine, if obstructive CAD cannot be ruled-out by coronary CTA, PET MPI using 15O-water is performed. The incremental prognostic value of PET imaging was tested using several ML models of which XGBoost models consistently outperformed others and were chosen for further analyses. XGBoost models were trained by using clinical data from medical records and coronary imaging findings: one set of models used all the available variables, while a second set of models used only clinical and CTA-based variables. Differences in the performances of the models were then used to assess the incremental value of PET perfusion variables in outcome prediction. Results After the removal of incomplete data entries, data from 2284 patients was retained for further analysis. During 8-year follow-up period 210 patients had a major cardiac event (these endpoints correspond to 59 myocardial infarctions, 35 unstable angina pectoris, and 116 deaths). The PET perfusion imaging data improved the predictive power of CTA during the first 4 years of observation time. After that, no significant difference in the predictive power was observed between the considered sets of XGBoost models, which either included or did not include PET perfusion data in the input variables. The highest area under the receiver operating characteristic curve (AUC) was at the observation time of 2 years (0.81, 95% CI 0.805–0.823) when PET data were included. The corresponding AUC when PET data were not included was at the observation time of 2 years (0.79, 95% CI 0.785–0.802). Conclusions Based on ML approach PET perfusion imaging improves the power in predicting cardiac events over anatomical CTA imaging for the first 4 years. The results illustrate the differences and complementary nature of anatomic and perfusion information in predicting outcome of patients with suspected CAD.

Impact of myocardial inflammation on quantitative myocardial perfusion at long-term follow-up - a descriptive hybrid PET/MR myocarditis study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation (SNSF). Background Whether myocardial inflammation causes long-term sequelae potentially affecting myocardial blood flow (MBF) is unknown. Objectives To assess the effect of myocardial inflammation on quantitative MBF parameters, as assessed by 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) late after myocarditis. Methods Fifty patients with a history of myocarditis underwent cardiac magnetic resonance (CMR) imaging at diagnosis and PET/MR imaging at follow-up at least 6 months later. Segmental MBF, myocardial flow reserve (MFR), and 13N-ammonia washout were obtained from PET, and segments with reduced 13N-ammonia retention, resembling scar, were recorded. Based on CMR, segments were classified as remote (n=469), healed (inflammation at baseline but no late gadolinium enhancement [LGE] at follow-up, n=118), and scarred (LGE at follow-up, n=72). Additionally, apparently healed segments but with scar at PET were classified as PET discordant (n=18). Results Compared to remote segments, healed segments showed higher stress MBF (2.71mL*min-1*g-1 [IQR 2.18–3.08] vs. 2.20 mL*min-1*g-1 [1.75–2.68], p&amp;lt;0.0001), MFR (3.78 [2.83–4.79] vs. 3.36 [2.60–4.03], p&amp;lt;0.0001) and washout (rest 0.24/min [0.18–0.31] and stress 0.53/min [0.40–0.67] vs. 0.22/min [0.16–0.27] and 0.46/min [0.32–0.63], p = 0.010 and p = 0.021, respectively). While PET discordant segments did not differ from healed segments regarding MBF and MFR, washout was higher by ∼30% (p&amp;lt;0.014). Finally, 10 (20%) patients were diagnosed by PET-MPI as presenting with myocardial scar but without corresponding LGE. Conclusions In patients with a history of myocarditis, quantitative measurements of myocardial perfusion as obtained from PET-MPI remain altered in areas initially affected by inflammation.

Hybrid CTA/PET imaging of coronary artery disease in non-diabetic, prediabetic and diabetic patients evaluated for chest pain

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Academy of Finland Finnish foundation for cardiovascular research. Background Patients with prediabetes or diabetes are at increased risk of developing cardiovascular disease and cardiac events. First-line coronary computed tomography angiography (CTA) followed by selective use of positron emission tomography (PET) myocardial perfusion imaging is a feasible strategy to diagnose and risk-stratify patients with suspected coronary artery disease (CAD). Purpose To study whether prediabetes or diabetes affects the relationship between imaging-defined CAD and patient outcome. Methods We retrospectively identified consecutive symptomatic patients who underwent coronary CTA for suspected CAD. In patients with suspected obstructive CAD on CTA, myocardial ischemia was routinely evaluated by 15O-water PET myocardial perfusion imaging. The relationship of CAD phenotype and long-term outcome was investigated according to patient’s diabetic status. A composite outcome included all-cause mortality, myocardial infarction (MI), and unstable angina pectoris. Results A total of 1743 patients were included: 1214 (70%) non-diabetic, 259 (15%) prediabetic, and 270 (16%) type 2 diabetic patients. During 6.43 years of follow-up, 164 (9%) adverse events occurred, including 106 deaths, 41 MIs and 17 episodes of unstable angina. The prevalence of normal coronary arteries on CTA was highest in the non-diabetic patients (39%). The prevalence of hemodynamically significant CAD (i.e., obstructive stenosis and abnormal perfusion) increased from 14% in non-diabetic patients to 20% in prediabetic and to 27% in diabetic patients. The lowest event rate was seen in patients with normal coronary arteries (annual event rate 0.2%) and highest in patients with concomitant type 2 diabetes and hemodynamically significant CAD (annual event rate 4.7%). However, neither prediabetes nor diabetes were independent predictors of the composite adverse outcome after adjustment for the clinical risk factors and imaging findings. Conclusions Coronary CTA followed by selective downstream use of PET myocardial perfusion imaging predicts long-term outcome similarly in type 2 diabetic, prediabetic, and non-diabetic patients.

Prognostic value of combined coronary CT angiography and myocardial perfusion imaging in women and men

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): State Research Funding for Turku University Hospital. Background Combined anatomical and functional imaging enables detection of non-obstructive and obstructive coronary artery disease (CAD) as well as myocardial ischemia, and also provides prognostic information. Purpose We evaluated sex differences in disease phenotype and adverse outcomes by using non-invasive combined anatomical and functional imaging in symptomatic patients with suspected CAD. Methods We retrospectively evaluated patients undergone coronary computed tomography angiography (CTA) for suspected CAD. According to local routine, patients with suspected obstructive stenosis on CTA were referred to downstream 15O-water positron emission tomography (PET) myocardial perfusion imaging to assess stress myocardial blood flow (MBF; ≤2.3 mL/g/min considered abnormal). A composite adverse endpoint was recorded, including all-cause death, myocardial infarction, and unstable angina pectoris. Results A total of 1948 patients (59% women) underwent coronary CTA of whom 657 (34%) patients underwent downstream PET perfusion imaging. During a mean follow-up of 6.8 years, 182 adverse events occurred. Women more often had normal coronary arteries (42% vs. 22%, p&amp;lt;0.001) and less often abnormal stress MBF (9% vs. 28%, p&amp;lt;0.001), as compared with men. The annual adverse event rate was lower in women versus men (1.2% vs. 1.7%, p = 0.02). Both in women and men, coronary calcification, non-obstructive CAD, and abnormal stress MBF were independent predictors of events. Abnormal stress MBF was associated with 5.0 and 5.6-fold adverse event rates in women and men, respectively. There was no statistical interaction between sex and coronary calcification, non-obstructive CAD, or abnormal stress MBF in terms of predicting adverse outcome. Conclusion Among patients evaluated for chronic chest pain, women have lower prevalence of ischemic CAD and lower rate of future adverse events. Combined coronary CTA and PET myocardial perfusion imaging predicts outcomes equally in women and men.

The impact of diabetes on the relationship of coronary artery disease and outcome: a study using multimodality imaging

BackgroundPatients with prediabetes or diabetes are at increased risk of developing cardiovascular disease and adverse outcomes. First-line coronary computed tomography angiography (CTA) followed by selective use of positron emission tomography (PET) myocardial perfusion imaging is a feasible strategy to diagnose and risk-stratify patients with suspected coronary artery disease (CAD). The aim of the present study was to study whether diabetes changes the relationship of CAD and long-term outcome.MethodsWe retrospectively identified consecutive symptomatic patients who underwent coronary CTA for suspected CAD. In patients with suspected obstructive CAD on CTA, myocardial ischemia was evaluated by 15O-water PET myocardial perfusion imaging. The relationship of the phenotype of CAD and long-term outcome in patients with no diabetes, prediabetes, or type 2 diabetes was investigated. A composite endpoint included all-cause mortality, myocardial infarction (MI), and unstable angina pectoris (UAP).ResultsA total of 1743 patients were included: 1214 (70%) non-diabetic, 259 (15%) prediabetic, and 270 (16%) type 2 diabetic patients. During 6.43 years of median follow-up, 164 adverse events occurred (106 deaths, 41 MIs, 17 UAPs). The prevalence of normal coronary arteries on CTA was highest in the non-diabetic patients (39%). The prevalence of hemodynamically significant CAD (abnormal perfusion) increased from 14% in non-diabetic patients to 20% in prediabetic and 27% in diabetic patients. The event rate was lowest in patients with normal coronary arteries and highest in patients with concomitant type 2 diabetes and hemodynamically significant CAD (annual event rate 0.2% vs. 4.7%). However, neither prediabetes nor diabetes were independent predictors of the composite adverse outcome after adjustment for the clinical risk factors and imaging findings.ConclusionsCoronary CTA followed by selective downstream use of PET myocardial perfusion imaging predicts long-term outcome similarly in non-diabetic and diabetic patients.

Characteristics and key differences between patient populations receiving imaging modalities for coronary artery disease diagnosis in the US

BackgroundThere are limited data on the impact of imaging modality selection for the assessment of coronary artery disease (CAD) risk on downstream resource utilisation. This study sought to identify differences between patient populations in the US undergoing stress echocardiography, single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), positron emission tomography (PET) MPI, and coronary computed tomography angiography (cCTA) for the assessment of CAD risk, and associated physician referral patterns.MethodsClaims and electronic health records data for 2.5 million US patients who received stress echocardiography, cCTA, SPECT MPI or PET MPI between January 2016 and March 2018, from the Decision Resources Group Real-World Evidence US Data Repository, were analysed. Patients were stratified into suspected and existing CAD cohorts, and further stratified by pre-test risk and presence and recency of interventions or acute cardiac events (within 1–2 years pre-index test). Linear and logistic regression were used to compare numeric and categorical variables.ResultsPhysicians were more likely to refer patients to standalone SPECT MPI (77%) and stress echocardiography (18%) than PET MPI (3%) and cCTA (2%). Overall, 43% of physicians referred more than 90% of their patients to standalone SPECT MPI. Just 3%, 1% and 1% of physicians referred more than 90% of their patients to stress echocardiography, PET MPI or cCTA. At the aggregated imaging level, patients who underwent stress echocardiography or cCTA had similar comorbidity profiles. Comorbidity profiles were also similar for patients who underwent SPECT MPI and PET MPI.ConclusionMost patients underwent SPECT MPI at the index date, with very few undergoing PET MPI or cCTA. Patients who underwent cCTA at the index date were more likely to undergo additional imaging tests compared with those who underwent other imaging modalities. Further evidence is needed to understand factors influencing imaging test selection across patient populations.

Myocardial perfusion imaging by 15O-H2O positron emission tomography predicts clinical revascularization procedures in symptomatic patients with previous coronary artery bypass graft.

We wanted to assess if 15O-H2O myocardial perfusion imaging (MPI) in a clinical setting can predict referral to coronary artery catheterization [coronary angiography (CAG)], execution of percutaneous coronary intervention (PCI), and post-PCI angina relief for patients with angina and previous coronary artery bypass graft (CABG). We analysed 172 symptomatic CABG patients referred for 15O-H2O positron emission tomography (PET) MPI at Aarhus University Hospital Department of Nuclear Medicine & PET Centre, of which five did not complete the scan. In total, 145 (87%) enrolled patients had an abnormal MPI. Of these, 86/145 (59%) underwent CAG within 3 months; however, no PET parameters predicted referral to CAG. During the CAG, 25/86 (29%) patients were revascularized by PCI. Relative flow reserve (RFR) (0.49 vs. 0.54 P = 0.03), vessel-specific myocardial blood flow (MBF) (1.53 vs. 1.88 mL/g/min, P < 0.01), and vessel-specific myocardial flow reserve (MFR) (1.73 vs. 2.13, P < 0.01) were significantly lower in patients revascularized by PCI. Receiver operating characteristic analysis of the vessel-specific parameters yielded optimal cutoffs of 1.36 mL/g/min (MBF) and 1.28 (MFR) to predict PCI. Angina relief was experienced by 18/24 (75%) of the patients who underwent PCI. Myocardial blood flow was an excellent predictor of angina relief on both a global [area under the curve (AUC) = 0.85, P < 0.01] and vessel-specific (AUC = 0.90, P < 0.01) level with optimal cutoff levels of 1.99 mL/g/min and 1.85 mL/g/min, respectively. For CABG patients, RFR, vessel-specific MBF, and vessel-specific MFR measured by 15O-H2O PET MPI predict whether subsequent CAG will result in PCI. Additionally, global and vessel-specific MBF values predict post-PCI angina relief.

Estimation of Microvascular Dysfunction by Using 13N-Ammonia Positron Emission Tomography with Quantitative Myocardial Blood Flow Analysis in Chronic Coronary Syndrome.

Although coronary artery disease (CAD) is characterized by epicardial atherosclerosis and microvascular disease, the importance of evaluating microvascular dysfunction has not been sufficiently recognized in clinical practice. We estimated microvascular disease severity by assessing hyperemic microvascular resistance (MVR), as determined by absolute quantification of myocardial blood flow (MBF) with 13N-ammonia positron emission tomography-myocardial perfusion imaging (PET-MPI). We retrospectively collected data for 23 CAD patients who underwent both stress/rest PET-MPI and invasive coronary angiography (CAG) with fractional flow reserve (FFR) measurement. Among 30 vessels for which FFR measurement was performed, 13 had a low FFR (FFR ≤0.75). For each patient, myocardial segments of a standard 17-segment model were assigned to the stenotic myocardial area perfused by the FFR-measured vessel and a reference normal-perfusion area based on PET-MPI and the coronary distribution on CAG. Hyperemic MVR was calculated by using the formula, hyperemic MVR = hyperemic mean blood pressure × FFR/hyperemic MBF of the stenotic vessel. A strong negative correlation was observed between hyperemic MVR and hyperemic MBF in the reference normal-perfusion area (R = -0.758, P<0.001). Microvascular disease severity in chronic CAD can be estimated by hyperemic MBF of the normal-perfusion area with 13N-ammonia PET-MPI.

Prognostic value of combined coronary CT angiography and myocardial perfusion imaging in women and men.

Combined anatomical and functional imaging enables detection of non-obstructive and obstructive coronary artery disease (CAD) as well as myocardial ischaemia. We evaluated sex differences in disease profile and outcomes after combined computed tomography angiography (CTA) and positron emission tomography (PET) perfusion imaging in patients with suspected obstructive CAD. We retrospectively evaluated 1948 patients (59% women) referred for coronary CTA due to suspected CAD during the years 2008-2016. Patients with a suspected obstructive lesion on coronary CTA (n = 657) underwent 15O-water PET to assess stress myocardial blood flow (MBF). During a mean follow-up of 6.8 years, 182 adverse events (all-cause death, myocardial infarction, or unstable angina) occurred. Women had more often normal coronary arteries (42% vs. 22%, P < 0.001) and less often abnormal stress MBF (9% vs. 28%, P < 0.001) than men. The annual adverse event rate was lower in women vs. men (1.2% vs. 1.7%, P = 0.02). Both in women and men, coronary calcification, non-obstructive CAD, and abnormal stress MBF were independent predictors of events. Abnormal stress MBF was associated with 5.0- and 5.6-fold adverse event rates in women and men, respectively. There was no interaction between sex and coronary calcification, non-obstructive CAD, or abnormal stress MBF in terms of predicting adverse events. Among patients evaluated for chronic chest pain, women have a lower prevalence of ischaemic CAD and a lower rate of adverse events. Combined coronary CTA and PET myocardial perfusion imaging predict outcomes equally in women and men.

Improved Performance of PET Myocardial Perfusion Imaging Compared to SPECT in the Evaluation of Suspected CAD.

Myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) has played a central role in the non-invasive evaluation of patients with obstructive coronary artery disease (CAD) for decades. In this review, we discuss the key differences and advantages of positron emission tomography (PET) MPI over SPECT MPI as it relates to the diagnosis, prognosis, as well as clinical decision-making in patients with suspected CAD. Stress-induced perfusion abnormalities on SPECT help estimate presence, extent, and location of ischemia and flow-limiting obstructive CAD, help with risk stratification, and serve as a gatekeeper to identify patients who will benefit from downstream revascularization versus medical management. Some of the major limitations of SPECT include soft-tissue attenuation artifacts, underestimation of ischemia due to reliance on relative perfusion assessment, and longer protocols with higher radiation dose when performed with traditional equipment. PET MPI addresses most of these limitations and offers better quality images, higher diagnostic accuracy along with shorter protocols and lower radiation dose to the patient. A special advantage of PET scanning lies in the ability to quantify absolute myocardial blood flow and assess true extent of epicardial involvement along with identifying non-obstructive phenotypes of CAD such as diffuse atherosclerosis and microvascular dysfunction. In addition, stress acquisition at/near peak stress with PET allows us to measure left ventricular ejection fraction reserve and myocardial blood flow reserve, which help with identifying patients at a higher risk of future cardiac events and optimally select candidates for revascularization. The several technical advantages of PET MPI position as a superior method to diagnose obstructive and non-obstructive phenotypes of ischemic heart disease affecting the entirety of the coronary circulation offer incremental value for risk stratification and guide post-test management strategy for patients with suspected CAD.

Advances in Digital PET Technology and Its Potential Impact on Myocardial Perfusion and Blood Flow Quantification.

In this review, we explore the development of digital PET scanners and describe the mechanism by which they work. We dive into some technical details on what differentiates a digital PET from a conventional PET scanner and how such differences lead to better imaging characteristics. Additionally, we summarize the available evidence on the improvements in the images acquired by digital PET as well as the remaining pitfalls. Finally, we report the comparative studies available on how digital PET compares to conventional PET, particularly in the quantification of coronary blood flow. The advent of digital PET offers high sensitivity and time-of-flight (TOF), which allow lower activity and scan times, with much less risk of detector saturation. This allows faster patient throughput, scanning more patients per generator, and acquiring more consistent image quality across patients. The higher sensitivity captures more of the potential artifacts, particularly motion-related ones, which presents a current challenge that still needs to be tackled. The digital silicon photomultiplier (SiPM) positron emission tomography (PET) machine has been an important development in the technological advancements of non-invasive nuclear cardiovascular imaging. It has enhanced the utility for PET myocardial perfusion imaging (MPI) and myocardial blood flow (MBF) quantification.