Pulmonary blood volume measured by 82Rb-PET in patients with chronic obstructive pulmonary disease: a retrospective cohort study.

In patients with chronic obstructive pulmonary disease (COPD), pulmonary vascular dysfunction and destruction are observable before the onset of detectable emphysema, but it is unknown whether this is associated with central hypovolemia. We investigated if patients with COPD have reduced pulmonary blood volume (PBV) evaluated by 82Rb-positron emission tomography (PET) at rest and during adenosine-induced hyperemia. This single-center retrospective cohort study assessed 6,301 82Rb-PET myocardial perfusion imaging (MPI) examinations performed over a 6-yr period. We compared 77 patients with COPD with 44 healthy kidney donors (controls). Cardiac output ([Formula: see text]) and mean 82Rb bolus transit time (MBTT) were used to calculate PBV. [Formula: see text] was similar at rest (COPD: 3,649 ± 120 mL vs. control: 3,891 ± 160 mL, P = 0.368) but lower in patients with COPD compared with controls during adenosine infusion (COPD: 5,432 ± 124 mL vs. control: 6,185 ± 161 mL, P < 0.050). MBTT was shorter in patients with COPD compared with controls at rest (COPD: 8.7 ± 0.28 s vs. control: 11.4 ± 0.37 s, P < 0.001) and during adenosine infusion (COPD: 9.2 ± 0.28 s vs. control: 10.2 ± 0.37 s, P < 0.014). PBV was lower in patients with COPD, even after adjustment for body surface area, sex, and age at rest [COPD: 530 (29) mL vs. 708 (38) mL, P < 0.001] and during adenosine infusion [COPD: 826 (29) mL vs. 1,044 (38) mL, P < 0.001]. In conclusion, patients with COPD show evidence of central hypovolemia, but it remains to be determined whether this has any diagnostic or prognostic impact.NEW & NOTEWORTHY The present study demonstrated that patients with chronic obstructive pulmonary disease (COPD) exhibit central hypovolemia compared with healthy controls. Pulmonary blood volume may thus be a relevant physiological and/or clinical outcome measure in future COPD studies.

Comparing various AI approaches to traditional quantitative assessment of the myocardial perfusion in [82Rb] PET for MACE prediction.

Assessing the individual risk of Major Adverse Cardiac Events (MACE) is of major importance as cardiovascular diseases remain the leading cause of death worldwide. Quantitative Myocardial Perfusion Imaging (MPI) parameters such as stress Myocardial Blood Flow (sMBF) or Myocardial Flow Reserve (MFR) constitutes the gold standard for prognosis assessment. We propose a systematic investigation of the value of Artificial Intelligence (AI) to leverage [ 82 Rb] Silicon PhotoMultiplier (SiPM) PET MPI for MACE prediction. We establish a general pipeline for AI model validation to assess and compare the performance of global (i.e. average of the entire MPI signal), regional (17 segments), radiomics and Convolutional Neural Network (CNN) models leveraging various MPI signals on a dataset of 234 patients. Results showed that all regional AI models significantly outperformed the global model ( p < 0.001 ), where the best AUC of 73.9% (CI 72.5-75.3) was obtained with a CNN model. A regional AI model based on MBF averages from 17 segments fed to a Logistic Regression (LR) constituted an excellent trade-off between model simplicity and performance, achieving an AUC of 73.4% (CI 72.3-74.7). A radiomics model based on intensity features revealed that the global average was the least important feature when compared to other aggregations of the MPI signal over the myocardium. We conclude that AI models can allow better personalized prognosis assessment for MACE.

Role of serial 18F-fludeoxyglucose positron emission tomography in determining the therapeutic efficacy of immunosuppression and clinical outcome in patients with cardiac sarcoidosis.

BACKGROUND: Myocardial inflammation and perfusion defects detected by 18F-fludeoxyglucose (FDG) and Rubidium-82 positron emission tomography (PET) may be associated with ventricular arrhythmias (VAs) in cardiac sarcoidosis (CS). The role of serial quantitative PET in determining the effect of treatment on myocardial inflammation and clinical outcomes is yet to be defined. METHODS: Newly diagnosed CS patients with active myocardial inflammation (maximum standardised uptake value (SUVmax) ≥ 2.5) were treated with immunosuppression, then underwent repeat FDG-PET, Rubidium-82, and echocardiographic imaging 6-12 months later. Serial changes in SUVmax, SUVmean, inflammatory extent, perfusion defect (PD) extent, metabolism/perfusion mismatch extent, global cardiac metabolic activity, and left ventricular ejection fraction (LVEF) were assessed. The primary endpoint was a composite of all-cause mortality, serious VA and heart-failure (HF) hospitalisation. Event data were recorded from the date of the second FDG-PET. RESULTS: The study population consisted of 113 patients (66% male, age: 55 ± 11 years, LVEF: 54 ± 13%). SUVmax reduced from 4.5 (interquartile range: 3.3-7.1) to 2.7 (2.2-3.6). Overall, 94 (83%) patients saw serial reduction in SUVmax, with 42 (37%) demonstrating complete response (SUVmax <2.5). Following a median of 46 (25-57) months, 28 (25%) patients reached the endpoint (8 deaths, 17 VAs, and 3 HF hospitalisations). PD extent (Hazard ratio 1.03, 95% confidence interval: 1.01-1.05; p = 0.035) was a significant predictor of outcome following treatment, even after accounting for LVEF and change in SUVmean. The risk of adverse events was the greatest in those with a pre-treatment or post-treatment PD extent of >10%. CONCLUSION: In our cohort with active CS, following a treatment-induced reduction in myocardial inflammation, PD extent was the main predictor of adverse events.

82-rubidium positron emission tomography determined myocardial flow reserve and outcomes following cardiac revascularisation - A multicentre registry study.

BACKGROUND: Finding patients with chronic coronary syndromes (CCS) whom revascularization could benefit, is complicated. Myocardial flow reserve (MFR), a measurement of myocardial perfusion, has proven prognostic value on survival and risk of major adverse cardiac events (MACE). We investigated if MFR identifies who may benefit from revascularization. METHODS: Among 7462 patients from Danish hospitals examined with 82Rb PET between January 2018 and August 2020, patients with ≥5% reversible perfusion defects were followed for MACE and all-cause mortality. Associations between revascularisation (within 90 days) and outcomes according to MFR (< and ≥ 2) was assessed by Cox regression adjusted by inverse probability weighting for demographics, cardiovascular risk factors, comorbidities, and 82Rb PET variables. RESULTS: Of 1806 patients with ≥5% reversible perfusion defect, 893 (49%) had MFR < 2 and 491 underwent revascularisation (36.6% in MFR < 2 versus 17.9% MFR ≥ 2, p < 0.001). During a median follow-up of 37.0 [31.0-45.8 IQR] months, 251 experienced a MACE and 173 died. Revascularisation was associated with lower adjusted risk of all-cause mortality (hazard ratio [HR], 0.51 [95% CI, 0.30-0.88], p = 0.015) and MACE (HR, 0.54 [0.33-0.87], p = 0.012) in patients with MFR < 2 but not MFR ≥ 2 for all-cause mortality (HR 1.33 [0.52-3.40], p = 0.542) and MACE (HR 1.50 [0.79-2.84], p = 0.211). MFR significantly modified the association between revascularisation and MACE, but not all-cause mortality (interaction p-value 0.021 and 0.094, respectively). CONCLUSIONS: Revascularization was associated with improved prognosis among patients with impaired MFR. No association was seen in patients with normal MFR. In patients with regional ischemia, MFR may identify patients with a prognostic benefit from revascularization.

Downward myocardial creep during stress PET imaging is inversely associated with mortality.

PURPOSE: The myocardial creep is a phenomenon in which the heart moves from its original position during stress-dynamic PET myocardial perfusion imaging (MPI) that can confound myocardial blood flow measurements. Therefore, myocardial motion correction is important to obtain reliable myocardial flow quantification. However, the clinical importance of the magnitude of myocardial creep has not been explored. We aimed to explore the prognostic value of myocardial creep quantified by an automated motion correction algorithm beyond traditional PET-MPI imaging variables. METHODS: Consecutive patients undergoing regadenoson rest-stress [82Rb]Cl PET-MPI were included. A newly developed 3D motion correction algorithm quantified myocardial creep, the maximum motion at stress during the first pass (60 s), in each direction. All-cause mortality (ACM) served as the primary endpoint. RESULTS: A total of 4,276 patients (median age 71 years; 60% male) were analyzed, and 1,007 ACM events were documented during a 5-year median follow-up. Processing time for automatic motion correction was < 12 s per patient. Myocardial creep in the superior to inferior (downward) direction was greater than the other directions (median, 4.2 mm vs. 1.3-1.7 mm). Annual mortality rates adjusted for age and sex were reduced with a larger downward creep, with a 4.2-fold ratio between the first (0 mm motion) and 10th decile (11 mm motion) (mortality, 7.9% vs. 1.9%/year). Downward creep was associated with lower ACM after full adjustment for clinical and imaging parameters (adjusted hazard ratio, 0.93; 95%CI, 0.91-0.95; p < 0.001). Adding downward creep to the standard PET-MPI imaging model significantly improved ACM prediction (area under the receiver operating characteristics curve, 0.790 vs. 0.775; p < 0.001), but other directions did not (p > 0.5). CONCLUSIONS: Downward myocardial creep during regadenoson stress carries additional information for the prediction of ACM beyond conventional flow and perfusion PET-MPI. This novel imaging biomarker is quantified automatically and rapidly from stress dynamic PET-MPI.

Impact on cardiovascular outcome of coronary revascularization-induced changes in ischemic perfusion defect and myocardial flow reserve.

PURPOSE: We evaluated the impact on cardiovascular outcome of coronary revascularization-induced changes in ischemic total perfusion defect (ITPD) and myocardial flow reserve (MFR) as assessed by 82Rb positron emission tomography (PET)/computed tomography (CT) imaging. METHODS: The study included 102 patients referred to 82Rb PET/CT myocardial perfusion imaging before and after coronary revascularization. All patients were followed for the occurrence of cardiovascular events (cardiac death, nonfatal myocardial infarction, repeated revascularization, and heart failure) after the second imaging study. RESULTS: During a median follow-up of 20 months, 21 events occurred. The clinical characteristics were comparable between patients with and without events. In the overall study population, after revascularization, there was a significant reduction (P < 0.001) of ITPD, while hyperemic myocardial blood flow (MBF) (P < 0.01) and MFR (P < 0.05) significantly improved. Event rate was higher in patients with ITPD (P < 0.005) or MFR (P < 0.001) worsening compared to those with unchanged or improved ITPD or MFR. At Cox univariable analysis, ITPD and MFR worsening resulted in predictors of events (both P < 0.05). Patients with worsening of both ITPD and MFR had the worst event-free survival (log-rank 32.9, P for trend < 0.001). CONCLUSIONS: In patients with stable CAD, worsening of ITPD and MFR after revascularization procedures is associated with higher risk of cardiovascular events. Follow-up MPI with 82Rb PET/CT may improve risk stratification in patients submitted to coronary revascularization.

Quantitative and qualitative comparison of Rubidium-82 and Oxygen-15 water cardiac PET.

BACKGROUND: Differences in tracer characteristics may influence the interpretation of positron emission tomography myocardial perfusion imaging (MPI). We compare the reading of MPIs with a low-extraction retention tracer (82Rb) and a high-extraction non-retention tracer (15O-water) in a selected cohort of patients with known coronary artery disease (CAD). METHODS: Thirty-nine patients with known CAD referred to 82Rb MPI due to angina underwent rest and stress imaging with both tracers and experienced MPI readers provided blinded consensus reads of all studies. In addition, a comparison of regional and global quantitative measures of perfusion was performed. RESULTS: The results showed 74 % agreement in the reading of 82Rb and 15O-water MPI for regional reversible ischemia and global disease, and 82 % agreement for regional irreversible ischemia. The 15O-water MPI identified more cases of global disease (n = 12 (15O-water) vs n = 4 (82Rb), p = 0.03), whereas differences in reversible ischemia (n = 22 vs n = 16, p = 0.11) and, irreversible ischemia (n = 8 vs n = 11, p = 0.45) were not significant. The correlation between myocardial blood flow measured using the two tracers was similar to previous studies (R2 = 0.78) with wide limits of agreement (-0.93 to 0.84 ml/g/min). CONCLUSIONS: Agreement between consensus readings of 82Rb and 15O-water MPI was good in patients with known CAD. In this limited size study, no significant differences in the identification of reversible and irreversible ischemia found, whereas 15O-water MPI had a higher positive rate for suspected global disease.

Coronary flow capacity and survival prediction after revascularization: physiological basis and clinical implications.

BACKGROUND AND AIMS: Coronary flow capacity (CFC) is associated with an observed 10-year survival probability for individual patients before and after actual revascularization for comparison to virtual hypothetical ideal complete revascularization. METHODS: Stress myocardial perfusion (mL/min/g) and coronary flow reserve (CFR) per pixel were quantified in 6979 coronary artery disease (CAD) subjects using Rb-82 positron emission tomography (PET) for CFC maps of artery-specific size-severity abnormalities expressed as percent left ventricle with prospective follow-up to define survival probability per-decade as fraction of 1.0. RESULTS: Severely reduced CFC in 6979 subjects predicted low survival probability that improved by 42% after revascularization compared with no revascularization for comparable severity (P = .0015). For 283 pre-and-post-procedure PET pairs, severely reduced regional CFC-associated survival probability improved heterogeneously after revascularization (P < .001), more so after bypass surgery than percutaneous coronary interventions (P < .001) but normalized in only 5.7%; non-severe baseline CFC or survival probability did not improve compared with severe CFC (P = .00001). Observed CFC-associated survival probability after actual revascularization was lower than virtual ideal hypothetical complete post-revascularization survival probability due to residual CAD or failed revascularization (P < .001) unrelated to gender or microvascular dysfunction. Severely reduced CFC in 2552 post-revascularization subjects associated with low survival probability also improved after repeat revascularization compared with no repeat procedures (P = .025). CONCLUSIONS: Severely reduced CFC and associated observed survival probability improved after first and repeat revascularization compared with no revascularization for comparable CFC severity. Non-severe CFC showed no benefit. Discordance between observed actual and virtual hypothetical post-revascularization survival probability revealed residual CAD or failed revascularization.

Myocardial creep and cardiorespiratory motion correction improves diagnostic accuracy of Rubidium-82 cardiac positron emission tomography.

AIM: To evaluate the feasibility of retrospectively detecting and correcting periodical (cardiac and respiratory motion) and non-periodical shifts of the myocardial position (myocardial creep) using only the acquired Rubidium-82 positron emission tomography raw (listmode) data. METHODS: This study comprised 25 healthy participants (median age = 23 years) who underwent repeat rest/adenosine stress Rubidium-82 myocardial perfusion imaging (MPI) and 53 patients (median age = 64 years) considered for revascularization who underwent a single MPI session. All subjects were evaluated for myocardial creep during MPI by assessing the myocardial position every 200 ms. A proposed motion correction protocol, including corrections for cardiorespiratory and creep motion (3xMC), was compared to a guideline-recommended protocol (StandardRecon). For the volunteers, we report test-retest repeatability using standard error of measurements (SEM). For the patient cohort, we evaluated the area under the receiver operating curve (AUC) for both stress and ischemic total perfusion deficits (sTPD and iTPD, respectively) using myocardial ischemia defined as fractional flow reserve values < 0.8 in the relevant coronary segment as the gold standard. RESULTS: Test-retest repeatability was significantly improved following corrections for myocardial creep (SEM; sTPD: StandardRecon = 2.2, 3xMC = 1.8; iTPD: StandardRecon = 1.6, 3xMC = 1.2). AUC analysis of the ROC curves revealed significant improvements for iTPD measurements following 3xMC [sTPD: StandardRecon = 0.88, 3xMC = 0.92 (P = .21); iTPD: StandardRecon = 0.88, 3xMC = 0.95 (P = .039)]. CONCLUSION: 3xMC has the potential to improve the diagnostic accuracy of myocardial MPI obtained from positron emission tomography. Therefore, its use should be considered both in clinical routine and large-scale multicenter studies.

Pulmonary blood volume assessment from a standard cardiac rubidium-82 imaging protocol: impact of adenosine-induced hyperemia.

BACKGROUND: This study aimed to assess the feasibility of estimating the pulmonary blood volume noninvasively using standard Rubidium-82 myocardial perfusion imaging (MPI) and characterize the changes during adenosine-induced hyperemia. METHODS: This study comprised 33 healthy volunteers (15 female, median age = 23 years), of which 25 underwent serial rest/adenosine stress Rubidium-82 MPI sessions. Mean bolus transit times (MBTT) were obtained by calculating the time delay from the Rubidium-82 bolus arrival in the pulmonary trunk to the arrival in the left myocardial atrium. Using the MBTT, in combination with stroke volume (SV) and heart rate (HR), we estimated pulmonary blood volume (PBV = (SV × HR) × MBTT). We report the empirically measured MBTT, HR, SV, and PBV, all stratified by sex [male (M) vs female (F)] as mean (SD). In addition, we report grouped repeatability measures using the within-subject repeatability coefficient. RESULTS: Mean bolus transit times was shortened during adenosine stressing with sex-specific differences [(seconds); Rest: Female (F) = 12.4 (1.5), Male (M) = 14.8 (2.8); stress: F = 8.8 (1.7), M = 11.2 (3.0), all P ≤ 0.01]. HR and SV increased during stress MPI, with a concomitant increase in the PBV [mL]; Rest: F = 544 (98), M = 926 (105); Stress: F = 914 (182), M = 1458 (338), all P < 0.001. The following test-retest repeatability measures were observed for MBTT (Rest = 17.2%, Stress = 17.9%), HR (Rest = 9.1%, Stress = 7.5%), SV (Rest = 8.9%, Stress = 5.6%), and for PBV measures (Rest = 20.7%, Stress = 19.5%) CONCLUSION: Pulmonary blood volume can be extracted by cardiac rubidium-82 MPI with excellent test-retest reliability, both at rest and during adenosine-induced hyperemia.

4D display of CT LV endocardial and epicardial models morphed from PET Rb-82 perfusion studies accurately quantifies segmental myocardial thickening.

BACKGROUND: MPI-derived LV wall thickening assessments for diagnostic purposes has been part of clinical guidelines for two decades. It relies on visual evaluation of tomographic slices or regional quantification displayed in 2D polar maps. 4D displays have not entered clinical usage nor have they been validated on their potential to provide equivalent information. The purpose of this work was to validate a 4D realistic display recently designed to quantitatively represent the thickening information from gated MPI into CT-morphed endocardial and epicardial moving surfaces. METHODS: Forty patients who underwent 82Rb PET were selected based on LV perfusion quantification. CTA templates of heart anatomy were selected to represent the LV anatomy. Generic CT-derived LV endocardial and epicardial surfaces were modified to represent the end diastolic (ED) phase according to PET-derived ED LV dimensions and wall thickness. These CT myocardial surfaces were then morphed by means of thin plate spline (TPS) techniques, according to the gated PET slices count changes (WThPET) and LV wall motion (WMoPET). A geometric thickening (GeoTh) equivalent to LV WThPET was defined on epicardial and endocardial CT surfaces over the cardiac cycle and the two measures compared. WThPET and GeoTh correlations were performed on a case-by-case basis, by segment and by pooling all 17 segments. Pearson's correlation coefficients (PCC) were calculated to assess the equivalence of the two measures. RESULTS: Two cohorts of patients (normal and abnormal) were identified based on SSS. R coefficients were as follows: for all pooled segments PCCstress and PCCrest were respectively 0.91 and 0.89 (normal), and 0.9 and 0.91 (abnormal); when individual 17 segments were considered mean PCCstress = 0.92 [0.81-0.98] and mean PCCrest = 0.93 [0.83-0.98] for the abnormal perfusion group; mean PCCstress = 0.89 [0.78-0.97] and mean PCCrest = 0.89 [0.77-0.97] for the normal. When individual studies were considered, R was always > .70 with the exception of five abnormal studies. Inter-user analysis was also conducted. CONCLUSIONS: Our novel technique for the visualization of LV wall thickening by means of 4D CT endocardial and epicardial surface models accurately replicated 82Rb slice thickening results showing promise for its usage for diagnostic purposes.

Exponential dosing to standardize myocardial perfusion image quality with rubidium-82 PET.

BACKGROUND: 82Rb PET is commonly performed using the same injected activity in all patients, resulting in lower image quality in larger patients. This study compared 82Rb dosing with exponential vs proportional functions of body weight on the standardization of myocardial perfusion image (MPI) quality. METHODS: Two sequential cohorts of N = 60 patients were matched by patient weight. Rest and dipyridamole stress 82Rb PET was performed using 0.1 MBq·kg-2 exponential and 9 MBq·kg-1 proportional dosing. MPI scans were compared qualitatively with visual image quality scoring (IQS) and quantitatively using the myocardium-to-blood contrast-to-noise ratio (CNR) and blood background signal-to-noise ratio (SNR) as a function of body weight. RESULTS: Average (min-max) patient body weight was 81 ± 18 kg (46-137 kg). Proportional dosing resulted in decreasing CNR, SNR, and visual IQS with increasing body weight (P < 0.05). Exponential dosing eliminated the weight-dependent decreases in these image quality metrics that were observed in the proportional dosing group. CONCLUSION: 82Rb PET dosing as an exponential (squared) function of body weight produced consistent stress perfusion image quality over a wide range of patient weights. Dramatically lower doses can be used in lighter patients, with the equivalent population dose shifted toward the heavier patients to standardize diagnostic image quality.

Patient-tailored risk assessment of obstructive coronary artery disease using Rubidium-82 PET-based myocardial flow quantification with visual interpretation.

INTRODUCTION: Our aim was to estimate the probability of obstructive CAD (oCAD) for an individual patient as a function of the myocardial flow reserve (MFR) measured with Rubidium-82 (Rb-82) PET in patients with a visually normal or abnormal scan. MATERIALS AND METHODS: We included 1519 consecutive patients without a prior history of CAD referred for rest-stress Rb-82 PET/CT. All images were visually assessed by two experts and classified as normal or abnormal. We estimated the probability of oCAD for visually normal scans and scans with small (5%-10%) or larger defects (> 10%) as function of MFR. The primary endpoint was oCAD on invasive coronary angiography, when available. RESULTS: 1259 scans were classified as normal, 136 with a small defect and 136 with a larger defect. For the normal scans, the probability of oCAD increased exponentially from 1% to 10% when segmental MFR decreased from 2.1 to 1.3. For scans with small defects, the probability increased from 13% to 40% and for larger defects from 45% to > 70% when segmental MFR decreased from 2.1 to 0.7. CONCLUSION: Patients with > 10% risk of oCAD can be distinguished from patients with < 10% risk based on visual PET interpretation only. However, there is a strong dependence of MFR on patient's individual risk of oCAD. Hence, combining both visual interpretation and MFR results in a better individual risk assessment which may impact treatment strategy.

Splenic switch-off in regadenoson 82Rb-PET myocardial perfusion imaging: assessment of clinical utility.

BACKGROUND: Splenic switch-off (SSO) is a phenomenon describing a decrease in splenic radiotracer uptake after vasodilatory stress. We aimed to assess the diagnostic utility of regadenoson-induced SSO. METHODS: We included consecutive patients who had clinically indicated Regadenoson Rb-82 PET-MPI for suspected CAD. This derivation cohort (no perfusion defects and myocardial flow reserves (MFR) ≥ 2) was used to calculate the splenic response ratio (SRR). The validation cohort was defined as patients who underwent both PET-MPI studies and invasive coronary angiography (ICA). RESULTS: The derivation cohort (n = 100, 57.4 ± 11.6 years, 77% female) showed a decrease in splenic uptake from rest to stress (79.9 ± 16.8 kBq⋅mL vs 69.1 ± 16.2 kBq⋅mL, P < .001). From the validation cohort (n = 315, 66.3 ± 10.4 years, 67% male), 28% (via SRR = 0.88) and 15% (visually) were classified as splenic non-responders. MFR was lower in non-responders (SRR; 1.55 ± 0.65 vs 1.76 ± 0.78, P = .02 and visually; 1.18 ± 0.33 vs 1.79 ± 0.77, P < .001). Based on ICA, non-responders were more likely to note obstructive epicardial disease with normal PET scans especially in patients with MFR < 1.5 (SRR; 61% vs 34% P = .05 and visually; 68% vs 33%, P = .01). CONCLUSION: Lack of splenic response based on visual or quantitative assessment of SSO may be used to identify an inadequate vasodilatory response.

Negative Predictive Value and Prognostic Associations of Rb-82 PET/CT with Myocardial Blood Flow in CAV.

BACKGROUND: Invasive coronary angiography (ICA) is the traditional screening modality for cardiac allograft vasculopathy (CAV). Positron emission tomography/computed tomography (PET/CT) scan with myocardial blood flow (MBF) quantification has emerged as a potential noninvasive alternative. OBJECTIVES: The aim of the study was to validate the diagnostic and prognostic value of a previously published algorithm for diagnosing CAV via PET/CT scans with MBF in a larger population. The study also sought to assess the downstream use of ICA when using PET/CT scanning as a screening modality. METHODS: Patients with heart transplantation without prior revascularization who underwent PET/CT scans with MBF were identified retrospectively. The accuracy of the algorithm was assessed in patients who underwent PET/CT scanning within 1 year of ICA. The prognostic value was assessed via a composite outcome of heart failure hospitalization, myocardial infarction, retransplantation, and all-cause mortality. RESULTS: A total of 88 patients for the diagnostic portion and 401 patients for the prognostic portion were included. PET CAV 0 had high negative predictive value for moderate to severe CAV (97%) and PET CAV 2/3 had a high positive predictive value for moderate to severe CAV (68%) by ICA. The cohort was followed for a median of 1.2 (IQR: 1.0-1.8) years with 46 patients having an adverse event. The annualized event rates were 6.9%, 9.3%, and 30.8% for PET CAV 0, 1, and 2/3, respectively (P < 0.001). CONCLUSIONS: An algorithm using PET/CT scanning with MBF demonstrates high a negative predictive value for CAV. PET CAV 2/3 is associated with a higher risk of adverse events and need for revascularization. PET/CT scanning with MBF is a reasonable alternative to ICA for screening for CAV.

Comparison of the prognostic value of impaired stress myocardial blood flow, myocardial flow reserve, and myocardial flow capacity on low-dose Rubidium-82 SiPM PET/CT.

BACKGROUND: The most reliable quantitative variable on Rubidium-82 (82Rb) cardiac PET/CT for predicting major adverse cardiovascular events (MACE) has not been characterized with low-dose silicon photomultipliers (SiPM) technology, which allows halving injected activity and radiation dose delivering less than 1.0 mSv in a 70-kg individual. METHODS AND RESULTS: We prospectively enrolled 234 consecutive participants with suspected myocardial ischemia. Participants underwent 82Rb cardiac SiPM PET/CT (5 MBq/kg) and were followed up for MACE over 652 days (interquartile range 559-751 days). For each participant, global stress myocardial blood flow (stress MBF), global myocardial flow reserve (MFR), and regional severely reduced myocardial flow capacity (MFCsevere) were measured. The Youden index was used to select optimal thresholds. In multivariate analysis after adjustments for clinical risk factors, reduced global stress MBF < 1.94 ml/min/g, reduced global MFR < 1.98, and regional MFCsevere > 3.2% of left ventricle emerged all as independent predictors of MACE (HR 4.5, 3.1, and 3.67, respectively, p < 0.001). However, only reduced global stress MBF remained an independent prognostic factor for MACE after adjusting for clinical risk factors and the combined use of global stress MBF, global MFR, and regional MFCsevere impairments (HR 2.81, p = 0.027). CONCLUSION: Using the latest SiPM PET technology with low-dose 82Rb halving the standard activity to deliver < 1 mSv for a 70-kg patient, impaired global stress MBF, global MFR, and regional MFC were powerful predictors of cardiovascular events, outperforming traditional cardiovascular risk factors. However, only reduced global stress MBF independently predicted MACE, being superior to global MFR and regional MFC impairments.

Prognostic implications of myocardial perfusion imaging by 82-rubidium positron emission tomography in male and female patients with angina and no perfusion defects.

AIMS: Myocardial perfusion imaging with 82-rubidium positron emission tomography (82Rb-PET) is increasingly used to assess stable coronary artery disease (CAD). We aimed to evaluate the prognostic value of 82Rb-PET-derived parameters in patients with symptoms suggestive of CAD but no significant reversible or irreversible perfusion defects. METHODS AND RESULTS: Among 3726 consecutive patients suspected of stable CAD who underwent 82Rb-PET between January 2018 and August 2020, 2175 had no regional perfusion defects. Among these patients, we studied the association of 82Rb-PET-derived parameters with a composite endpoint of all-cause mortality, hospitalization for unstable angina pectoris, acute myocardial infarction, heart failure, or ischaemic stroke. During a median follow up of 1.7 years (interquartile range 1.1-2.5 years), there were 148 endpoints. Myocardial blood flow (MBF) reserve (MFR), MBF during stress, left ventricular ejection fraction (LVEF), LVEF-reserve, heart rate reserve, and Ca score were associated with adverse outcomes. In multivariable Cox model adjusted for patient and 82Rb-PET characteristics, MFR < 2 (hazard ratio (HR) 1.75, 95% confidence interval (CI) 1.24-2.48), LVEF (HR 1.38 per 10% decrease, 95% CI 1.24-1.54), and LVEF-reserve (HR 1.19 per 5% decrease, 95% CI 1.07-1.31) were significant predictors of endpoints. Results were consistent in subgroups defined by gender, history of ischaemic heart disease, low LVEF, and atrial fibrillation. CONCLUSION: MFR, LVEF, and LVEF-reserve derived from 82Rb-PET provide prognostic information on cardiovascular outcomes in patients with no perfusion defects. This may aid in identifying patients at risk and might provide an opportunity for preventive interventions.