Myocardial Flow Reserve Values Research Articles

Prognostic Value of Simultaneous Analysis with Myocardial Flow Reserve and Right Ventricular Strain by Hybrid 13N-Ammonia Positron Emission Tomography/Magnetic Resonance Imaging in Coronary Artery Disease.

Myocardial flow reserve (MFR) derived from 13N-ammonia positron emission tomography (PET) is used to predict adverse cardiac events in patients with coronary artery disease (CAD). Right ventricular global longitudinal strain (RVGLS) measured by magnetic resonance imaging (MRI) is used to evaluate RV function and predict cardiac events. This study aimed to evaluate the prognostic value of MFR and RVGLS measured by hybrid 13N-ammonia PET/MRI in patients with CAD.Sixty-one patients who underwent 13N-ammonia PET/MRI were analyzed. The end points were defined as a composite of all-cause death, myocardial infarction, sustained ventricular arrhythmia, hospitalization due to decompensated heart failure, and revascularization. At a follow-up of 2.8 ± 1.9 years, 21 events had occurred. Kaplan-Meier analysis showed that the event-free rate was significantly lower in the group with MFR < 1.80 than in that with MFR ≥ 1.80 (P < 0.001). Additionally, the event-free rate was significantly lower in the group with RVGLS > -18.22% than in that with RVGLS ≤ -18.22% (P = 0.025). After dividing the patients into 4 groups by the median MFR and the median RVGLS, the event-free rate was lowest in the combined group of MFR < 1.80 and RVGLS > -18.22% than any other groups (P < 0.001). In a Cox proportional hazard analysis, MFR and RVGLS were independent predictors of cardiac adverse events in the patients with CAD.The simultaneous assessment of MFR and RVGLS by 13N-ammonia PET/MRI revealed the feasibility of precise risk stratification for cardiac events in patients with CAD.

Abstract 9916: Prognostic Value of Simultaneous Analysis With Myocardial Flow Reserve and Right Ventricular Strain by Hybrid 13 N-ammonia Positron Emission Tomography/Magnetic Resonance Imaging in Coronary Artery Disease

Introduction: Myocardial flow reserve (MFR) derived from 13 N-ammonia positron emission tomography (PET) is used to predict adverse cardiac events in the patients with coronary artery disease (CAD). Right ventricular (RV) strain measured by magnetic resonance imaging (MRI) is used to evaluate RV function. This study aimed to evaluate the prognostic value of combined MFR and RV strain measured by hybrid 13 N-ammonia PET/MRI in patients with CAD. Methods: Sixty-one patients who underwent 13 N-ammonia PET/MRI were enrolled. MFR was calculated from dynamic acquisition of 13 N-ammonia PET under vasodilator stress with intravenous injection of adenosine. RV global longitudinal strain (GLS) was measured by wall motion tracking techniques in cine-mode MRI. The end points were defined as a composite of all-cause death, myocardial infarction, sustained ventricular arrhythmia, hospitalization due to decompensated heart failure, and revascularization. Results: At a follow-up of 2.8 ± 1.9 years, 21 events occurred. Kaplan-Meier analysis showed that the event-free rate was significantly lower in the group with MFR &lt; 1.80 than that with MFR ≥ 1.80 (P &lt; 0.001, Figure a). Additionally, the event-free rate was significantly lower in the group with RVGLS &gt; –18.22% than that with RVGLS ≤ –18.22% (P = 0.025, Figure b). After dividing the patients into four groups by the median MFR and the median RVGLS, the event-free rate was lowest in the combined group of MFR &lt; 1.80 and RVGLS &gt; -18.22% than any other groups (P &lt; 0.001, Figure c). In the Cox proportional hazard analysis, MFR and RVGLS were independent predictors of cardiac adverse events in the patients with CAD. Conclusion: The simultaneous assessment of MFR and RV strain by 13 N-ammonia PET/MRI revealed the feasibility of precise risk stratification for cardiac events in patients with CAD.

Prognostic value of myocardial flow reserve obtained by 82-rubidium positron emission tomography in long-term follow-up after heart transplantation

BackgroundCardiac allograft vasculopathy (CAV) is a leading cause of death following heart transplantation (HTx) and non-invasive prognostic methods in long-term CAV surveillance are needed. We evaluated the prognostic value of myocardial flow reserve (MFR) obtained by 82-rubidium (82Rb) positron emission tomography (PET). MethodsRecipients undergoing dynamic rest-stress 82Rb PET between April 2013 and June 2017 were retrospectively evaluated in a single-center study. Evaluation by PET included quantitative myocardial blood flow and semiquantitative myocardial perfusion imaging. Patients were grouped by MFR (MFR ≤ 2.0 vs MFR > 2.0) and the primary outcome was all-cause mortality. ResultsA total of 50 patients (68% men, median age 57 [IQR: 43 to 68]) were included. Median time from HTx to PET was 10.0 (6.7 to 16.0) years. In 58% of patients CAV was documented prior to PET. During a median follow-up of 3.6 (2.3 to 4.3) years 12 events occurred. Survival probability by Kaplan–Meier method was significantly higher in the high-MFR group (log-rank P = .02). Revascularization (n = 1), new CAV diagnosis (n = 1), and graft failure (n = 4) were more frequent in low-MFR patients. No retransplantation occurred. ConclusionsMyocardial flow reserve appears to offer prognostic value in selected long-term HTx recipients and holds promise as a non-invasive method for CAV surveillance possibly guiding management strategy.

Integration of quantitative absolute myocardial blood flow estimates from dynamic CZT-SPECT improves the detection of coronary artery disease

BackgroundBalanced ischemia with multi-vessel coronary artery disease (CAD) is difficult to diagnose with semiquantitative single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Dynamic cardiac SPECT provides quantitative estimations of stenosis severity and ischemic burden by assessing myocardial flow reserve (MFR) and myocardial blood flow (MBF). The aim of this study was to evaluate the incremental value of dynamic SPECT in multi-vessel coronary artery disease (CAD). MethodsPatients with suspected CAD who underwent dynamic ECG-gated dipyridamole MPI and coronary angiography within 6 months were retrospectively reviewed. The performance of summed stress, rest and difference scores (SSS, SRS, SDS), post-stress and resting MBF (MBFs, MBFr) and MFR were compared at both patient level and vessel level. ResultsIn 32 patients with 39 stenotic vessels, 12 had three-vessel disease (38%). Globally increased SSS and impaired MBF values were significantly associated with significant CAD at the patient level, but SDS and MFR were not. Regional increases in SSS and reductions in both MBFs and MBFr were significantly associated with stenotic vessels. The best cutoff value of global MBFs to predict CAD was 3.5 ml·g−1·min−1 (area under the curve, AUC = .84, P = .002). The best cutoff value of regional MBFs to detect significant stenosis was 3.6 ml·g−1·min−1 (AUC = .74, P < .001). However, the best possible cut-off values of MFR were not found. Sex-difference in both global and regional MBFr but MBFs was found, which might result in the non-significance in MFR. ConclusionsThis study validated a clinically available method to quantify MFR using dynamic CZT-SPECT. This method improved the detectability of multi-vessel CAD, and absolute MBFs was superior to MFR and other semiquantitative MPI parameters.

13N-ammonia positron emission tomography-derived endocardial strain for the assessment of ischemia using feature-tracking in high-resolution cine imaging

BackgroundAssessing endocardial strain using a single 13N-ammonia positron emission tomography (PET) scan would be clinically useful, given the association between ischemia and myocardial deformation. However, no software has been developed for strain analysis using PET. We evaluated the clinical potential of feature tracking-derived strain values measured using PET, based on associations with the myocardial flow reserve (MFR). Methods and ResultsThis retrospective study included 95 coronary artery disease patients who underwent myocardial 13N-ammonia PET. Semi-automatic measurements were made using a feature-tracking technique during myocardial cine imaging, and values were calculated using a 16-segment model. Adenosine-stressed global circumferential strain (CS) and global longitudinal strain (LS) values were compared with global MFR values. Stressed and resting global strain values were also compared. Global strain values were significantly lower in 39 patients with abnormal MFRs [< 2.0] than in 56 patients with normal MFRs [≥ 2.0]. The global CS values in the stressed state were significantly decreased than the resting state values in patients with abnormal MFRs. ConclusionsThis study applied endocardial feature-tracking to 13N-ammonia PET, and the results suggested that blood flow and myocardial motility could be clinically assessed in ischemic patients using a single PET scan.

Myocardial flow reserve estimation with contemporary CZT-SPECT and 99mTc-tracers lacks precision for routine clinical application

BackgroundPET 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. MethodsValidation 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. ResultsBased 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. ConclusionsCurrent SPECT-derived estimates of MFR lack precision and require further optimization for clinical risk stratification.

Incremental prognostic value of digital positron emission tomography derived myocardial flow reserve: A prospective cohort study

BackgroundPositron Emission Tomography (PET) Myocardial Perfusion Imaging (MPI) is a robust diagnostic and prognostic test in patients with suspected or known coronary artery disease (CAD). We aimed to assess the incremental prognostic value of myocardial flow reserve (MFR) using the latest generation of digital PET scanners. MethodsConsecutive patients with clinically indicated PET MPI for suspected or known CAD were included. Myocardial blood flow (MBF) in ml/min/g was obtained from dynamic images at rest and peak hyperemia, and the myocardial flow reserve (MFR) was calculated as the ratio of stress to rest MBF. Patients were followed from the date of PET imaging for the occurrence of the primary outcome (composite of all-cause death, myocardial infarction, and Percutaneous Coronary Intervention or Coronary Artery Bypass Graft occurring >90 days after imaging). Nested multivariable Cox regression models were used to assess the incremental prognostic role of MFR over traditional risk factors and PET relative perfusion parameters. ResultsThe final cohort consisted of 3534 patients (mean age 67 ± 12 years, 48% female, 67% Caucasian, 53% obese, 55% hypertension, 32% diabetes, 42% dyslipidemia). During a median follow-up of 8.5 (3.0–15.4) months, 229 patients (6.5%, 6.4 per 1000 person-years) experienced the primary outcome. In nested multivariable Cox models, impaired MFR (MFR < 2) was significantly associated with the primary outcome (HR 2.9, 95% CI 2.0–4.1, p < 0.001) and significantly improved discrimination (Harrell's C 0.77, p = 0.002). ConclusionMFR derived from digital PET scanners has an independent and incremental prognostic role in patients with suspected or known CAD.

The myocardial flow reserve in patients with heart failure with preserved ejection fraction.

To evaluate the myocardial flow reserve (MFR) and myocardial blood flow (MBF) parameters in patients with heart failure with preserved ejection fraction (HFpEF) and to assess their relationship with the severity of HF and the levels of soluble ST2 (sST2). A total of 59 consecutive patients (median age of 65.0 (58.0; 69.0) years) with non-obstructive coronary artery disease (CAD) and preserved EF were enrolled. Serum levels biomarkers were measured by enzyme immunoassay. MBF and MFR parameters were evaluated by dynamic CZT-SPECT. All patients were divided into two groups: group 1 comprised patients (n = 41) with HFpEF, and group 2 comprised those (n = 18) without HFpEF. In group 1 global MFR (gMFR) values were lower by 27.8% (p = 0.003) than in group 2. The values of gMFR correlated with NT-proBNP (r = -0.290) and sST2 (r = -0.331) levels. Based on ROC-analysis, gMFR ≤ 2.27 (AUC = 0.746; p < 0.001) were associated with the presence of HFpEF. In patients with HFpEF (n = 41) the values of gMFR were related to NYHA classes (p < 0.001) and the parameters of diastolic dysfunction (p < 0.001). The values of gMFR ≤ 2.27 may be used for the evaluation of microvascular changes in patients with HFpEF and non-obstructive CAD.

Quantification of myocardial blood flow and myocardial flow reserve by 13N-NH3 PET/CT is not significantly affected by pixel size.

Myocardial blood flow (MBF) and myocardial flow reserve (MFR) are measurable by 13N-NH3 positron emission tomography (PET). MFR, which is the ratio of MBF under adenosine stress to MBF at rest, is prognostically valuable. The ASNC imaging guidelines/SNMMI procedure standards recommend using 2-3mm pixels, and pixel size does differ between institutions. We sought to evaluate the effects of pixel sizes on the quantitative values calculated from 13N-NH3 PET images. Thirty consecutive patients with ischemic heart disease who underwent 13N-NH3 PET were retrospectively enrolled. Dynamic images were quantified using PMOD's cardiac PET analysis tool (pixel sizes: 3.18, 2.03, and 1.59mm). MBF under adenosine stress, MBF at rest, and MFR for the right coronary artery (RCA) region, left anterior descending artery region, and left circumflex coronary artery branch region innervation regions were calculated at each pixel size and compared. Quantitative values did not significantly differ according to pixel size in any of the regions. However, MFR values for the RCA fluctuated the most. Ischemic and non-ischemic regions remained visually discernible in qualitative images, with no variation in quantitative values, regardless of pixel size. Quantitative values were not significantly affected by pixel sizes within the recommended range of 2-3mm. Values for the RCA region may have been overestimated, but this was true for all pixel sizes.

CORONARY ATHEROSCLEROSIS ASSESSMENT: A NEW ANATOMICAL, FUNCTIONAL, MORPHOLOGICAL AND BIO-MECHANICAL APPROACH

The aims of this work are to investigate and compare two different flow dynamics techniques (steady state - pulsatile flow) for endothelial shear stress calculation, compare lesion specific smartFFR and ESS values, as well as total vessel smartFFR and ESS values, and investigate the relationship between smartFFR and ESS to stress MBF (myocardial blood flow) and MFR (myocardial flow reserve). A total of 10 coronary vessels of 6 patients with intermediate pre-test likelihood for coronary artery disease, who have undergone both CTCA and PET-MPI with 15O-water or 13N-ammonia, were included in the study. Seven (7) cases had normal stress MBF and MFR values and three (3) had abnormal ones. PET was considered abnormal when &gt; 1 contiguous segments showed both stress MBF ≤2.3mL/g/min and MFR ≤2.5 for 15O-water or 1.79 mL/g/min and ≤2.0 for 13N-ammonia, respectively. The ESS at the luminal surface of the artery was calculated as the product of viscosity and the gradient of blood velocity near the vessel wall. To calculate the smartFFR, we performed a transient simulation for each case. We used a pressure of 100 mmHg as a boundary condition at the inlet (i.e. mean human aortic pressure). At the outlet, a flow profile of 4 timesteps with a timestep duration of 0.25 sec was used. In each timestep, a volumetric flow rate of 1, 2, 3 and 4 ml/s are applied as outlet boundary conditions. The cut-off value for a pathological smartFFR is 0.83. There is a difference in total vessel calculated smartFFR results compared to the corresponding values of lesion specific smartFFR (0.88 vs 0.97, p=0.01). For ESS there is a negligible difference between lesion specific and total vessel values (2.22 vs 2.74, p = 0.9). There is a moderate negative correlation between both lesions specific (r = -0.543) and total vessel smartFFR and ESS (r = -0.915). ESS values were higher in vessels where vessel smartFFR was considered abnormal (1.97 vs 5.52, p = 0.01). Total vessel length smartFFR was lower in vessels with abnormal PET-MPI compared to the normal vessels (0.75 vs 0.93, p = 0.01). ESS is higher in vessels with pathological stress MBF and CFR (5.5 vs 2.0, p = 0.02). The total vessel length smartFFR and lesion ESS appear to assess the functional significance of the vessel well, when compared to the PET-MPI measurements.

13N-ammonia PET-derived right ventricular longitudinal strain and myocardial flow reserve in right coronary artery disease.

We developed a feature-tracking algorithm for use with electrocardiography-gated high-resolution 13N-ammonia positron emission tomography (PET) imaging, and we hypothesized it could be used to clarify the association between right ventricular (RV) longitudinal strain (LS) and right coronary artery (RCA) ischemia. The aim of this study was to investigate the association between the reduction of regional myocardial flow reserve (MFR) in RCA territories and PET-derived LS of the RV free wall. Ninety-three patients with coronary artery stenosis > 50%, diagnosed by coronary computed tomography angiography, and 10 controls were retrospectively analyzed. RV-LS in the free wall was measured by a feature-tracking technique on the resting and stressed 13N-ammonia PET images of horizontal long axis slices. The patients were sub-grouped according to regional MFR values at the territories of RCA, left anterior descending artery (LAD), and left circumflex coronary artery (LCx): RCA-MFR < 2.0 [n = 34], RCA-MFR ≥ 2.0 but MFR < 2.0 at LAD or LCx territories [n = 11], and MFR ≥ 2.0 for all territories [n = 48]. Stress and resting RV-LS were compared in each of the four groups. Multiple comparisons of RV-LS among the four groups were performed in the stress and resting state. Decreased stress RV-LS in patients with an RCA-MFR < 2.0 was observed. In the patients with MFR ≥ 2.0 for all territories, the stressed RV-LS was significantly increased compared to that in the resting state. Significantly decreased RV free wall LS during adenosine stress in patients with RCA-MFR < 2.0 was observed in the other three groups. We measured RV myocardial LS using feature tracking in cine imaging of 13N-ammonia PET. The results of this study suggest that PET-derived stressed RV-LS is useful for detecting reduced RV myocardial motion due to ischemia in the RCA territory.

PROGNOSTIC VALUE OF PET MPI MYOCARDIAL FLOW RESERVE IN CABG PATIENTS

<h3>BACKGROUND</h3> Positron emission tomography (PET) myocardial perfusion imaging (MPI) is a well-validated non-invasive imaging technique for the assessment of coronary artery disease (CAD). Amongst its many advantage, it permits quantitative, non-invasive assessment of myocardial blood flow (MBF) and myocardial flow reserve (MFR). While the diagnostic and prognostic value of MFR has been extensively validated in the general CAD population, only limited data is available when it comes to its prognostic value in patients with prior coronary artery bypass grafting (CABG). Our study aim was to evaluate if diminished MFR on 13N-Ammonia PET MPI is associated with increased risk of major adverse cardiovascular events (MACE) amongst patients with prior CABG. <h3>METHODS AND RESULTS</h3> A retrospective study was performed at the Montréal University Hospital Centre (CHUM) between February 2018 and September 2020. Patients (n=62) with prior CABG (at least 3 months) who had an 13N-Ammonia PET/CT scan performed were included. The main endpoint was to evaluate if myocardial perfusion values were associated with increased risk of MACE. MACE was defined as death, re-infarction, repeat revascularization or hospitalization for heart failure. In patients with multiple MACE, only the first event was considered for analysis. Our cohort was subdivided in two groups: patients with MACE and patients without MACE. The main indications for performing PET MPI are displayed in the figure. Baseline characteristics (table) were comparable between both groups except for the number of graft (3.0 [2.0,3.0] vs. 3.0 [3.0,4.0], p=0.005). Risk factors were similar between both groups except for presence of chronic kidney disease (CKD) (11 (55%) vs. 10 (23.8%), p=0.02). There was no difference between both groups regarding drug regimen. In patients with MACE as compared to no-MACE, both global MFR (1.8 ± 0.5 vs. 2.1 ± 0.5, p=0.03, respectively) and the global stress MBF (1.2 [0.9,1.4] vs. 1.4 [1.1,1.8] mL/min/g, p=0.049, respectively) were significantly lower. Sum Stress Score was higher in the MACE group (2.5 [1.0,10.0] vs. 0.0 [0.0,3.5], p=0.04). Low left ventricular ejection fraction (LVEF) reserve had no prognostic value in our study (p=0.20). <h3>CONCLUSION</h3> In patients with prior CABG, both reduced global MFR and global stress MBF were associated with increased risk of MACE. Therefore, PET MPI with flow quantification can help identifying patients at risk of MACE after CABG. Our findings need to be confirmed in a larger cohort of patients.

Functional Assessment of Coronary Artery Disease by Myocardial Flow Reserve Versus Pressure-wire Based Assessment: A Systematic Review.

Positron emission tomography (PET) permits the noninvasive quantification of myocardial blood flow (MBF). Myocardial flow reserve (MFR), calculated by dividing stress MBF by rest MBF is a reliable index for the functional information of coronary artery disease. A pressure-derived physiological index, such as fractional flow reserve (FFR) is also an important measurement. Both MFR and FFR values are used to evaluate coronary physiology; however, but they are not interchangeable because each test has certain discrepancies. In this systematic review, we provide an overview of coronary physiology with PET compared to pressure-derived physiological indices.

Value of regional myocardial flow measurements using Rubidium-82 PET

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The combination of myocardial blood flow (MBF) measurements using Rubidium-82 (Rb-82) PET and visual assessment of the PET images is increasingly used due to its high diagnostic and prognostic value. Typically, flow measurements are calculated and used for the myocardium as a whole (global). However, small regional flow deficits may go unnoticed when only looking at global flow values. Purpose To compare the diagnostic value of regional and global myocardial flow measurements using Rb-82 PET in the detection of obstructive CAD. Methods We retrospectively included 1034 patients with no history of coronary artery disease (CAD) referred for rest and regadenoson-induced stress Rb-82 PET/CT. MBFs were calculated using Lortie’s one-tissue compartment model. Myocardial flow reserve (MFR) was calculated as the ratio of MBF during stress and rest. Regional flow was determined per vessel and per segment. Vessel MFR was defined as the lowest flow reserve of LAD, LCX and RCA territories and segmental MFR as the lowest flow reserve in all 17 segments. Follow-up data were obtained from medical records. Patients were classified to have obstructive CAD if follow-up included a positive invasive coronary angiography (ICA), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or all cause death. Receiver-operating characteristic (ROC) analyses were constructed to compare the diagnostic value of global and regional flow values. Results Follow-up was obtained in all 1034 patients and the median follow-up time was 2.1 years. Myocardial flow reserve values were significantly lower (p &amp;lt; 0.001) in the 128 patients classified with obstructive CAD than in the 906 patients without obstructive CAD: global MFR (median 1.9 [interquartile range 1.6-2.4] vs. 2.5 [2.1-2.9]); vessel MFR (1.6 [1.3-2.1] vs. 2.3 [1.9-2.6]); Segmental MFR (1.3 [0.9-1.7] vs. 1.9 [1.6-2.2]). The area under the curve of vessel MFR (0.79 ± 0.02) and segmental MFR (0.81 ± 0.02) were similar but significantly (p &amp;lt; 0.001) larger than the area of global MFR (0.75 ± 0.03), as shown in the Figure. Conclusion The diagnostic value improved with the use of regional MFR instead of global MFR measurements in the detection of obstructive CAD. Therefore, it seems that visual assessment of PET images can best be combined with regional flow measurements either on a per vessel or a per segment basis in Rubidium-82 PET myocardial perfusion imaging.

Risk stratification in coronary artery disease using NH3-PET myocardial flow reserve and CAD-RADS on coronary CT angiography.

Myocardial flow reserve (MFR) derived from 13N-ammonia positron emission tomography (NH3-PET) can predict the prognosis of patients with various heart diseases. Coronary computed tomography angiography (CCTA) is a non-invasive investigation for ischemic heart disease. The coronary artery disease reporting and data system (CAD-RADS) was established to standardize and facilitate the reporting of CCTA data regarding CAD. This study aimed to investigate the prognostic value of CAD-RADS and MFR. A total of 133 patients who underwent NH3-PET and CCTA within 3months were enrolled. Patients were divided into groups with CAD-RADS 0-2 and ≥ 3 and into groups with MFR ≥ 2.0 and < 2.0. The endpoint was major adverse cardiac events (MACE) comprising all-cause death, acute coronary syndrome, hospitalization due to heart failure, and cerebrovascular disease. The ability of CAD-RADS and MFR to predict MACE was analyzed using Kaplan-Meier analysis. There was no significant difference in MFR between patients with CAD-RADS 0-2 and ≥ 3 (2.3 ± 0.9 vs. 2.2 ± 0.7, p = 0.50). The MACE rate for patients with CAD-RADS 0-2 and ≥ 3 was equivalent (log-rank test, p = 0.64). Patients with MFR < 2.0 had a significantly higher MACE rate than those with MFR ≥ 2.0 (p = 0.017). In patients with CAD-RADS ≥ 3, patients with MFR < 2.0 had a significantly higher MACE rate than those with MFR ≥ 2.0 (p = 0.034). CAD-RADS did not contribute to MACE prediction. Conversely, MFR was useful in predicting MACE, allowing for further risk stratification in addition to CAD-RADS.

Myocardial Flow Reserve and Coronary Calcification in Prognosis of Patients With Suspected Coronary Artery Disease

ObjectivesThe aim of this analysis is to examine the incremental prognostic value of coronary artery calcium (CAC) score and myocardial flow reserve (MFR) in patients with suspected coronary artery disease (CAD) undergoing positron emission tomography (PET) myocardial perfusion imaging (MPI). BackgroundAdvances in cardiac PET and computed tomography imaging enabled the simultaneous acquisition of anatomic and physiological data for patients suspected of CAD. MethodsConsecutive patients who underwent PET MPI and CAC score calculation at King Abdulaziz Cardiac Center, Riyadh, Saudi Arabia, between May 2011 and May 2018 were included in the study. MPI and CAC images were obtained in the same setting. The primary endpoint of the study was a composite of cardiac death and nonfatal myocardial infarction. Cox proportional hazard regression was used to assess the incremental prognostic value of CAC and MFR by sequentially adding the variables to a model that included clinical and PET variables. ResultsA total of 4,008 patients (mean age 59.7 ± 11.6 years, 55% women) were included in the analysis. Risk factors were prevalent (77.6% hypertension, 58.1% diabetes). In total, 35.9% of the cohort had CAC of 0, 16.5% had CAC ≥400, and 43.9% had MFR <2. Over a median follow up of 1.9 years, 130 (3.2%) patients had cardiac death/nonfatal myocardial infarction. CAC and MFR score added incremental prognostic value over clinical and perfusion variables (base model: c-index 0.8137; Akaike information criterion [AIC]: 1,865.877; p = 0.0011; CAC model: c-index = 0.8330; AIC: 1,850.810; p = 0.045 vs. base model; MFR model: c-index = 0.8279; AIC: 1,859.235; p = 0.024). Combining CAC and MFR did not enhance risk prediction (c-index = 0.8435; AIC: 1,846.334; p = 0.074 vs. MFR model; p = 0.21 vs. CAC model.) ConclusionsIn this large cohort of patients referred for PET MPI, both CAC and MFR independently added incremental prognostic value over clinical and MPI variables. Although combining both may have synergetic prognostic effect, this relation was not shown in multivariable model of this analysis.

The usage CZT SPECT to assess myocardial blood flow and flow reserve in myocardial infarction with non-obstructive coronary arteries patients

Abstract Funding Acknowledgements Type of funding sources: None. Background. Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) is currently of interest in terms of a small amount of data related to myocardial perfusion, myocardial blood flow (MBF) and myocardial flow reserve (MFR). Purpose. To assess the severity of myocardial perfusion, MBF and MFR impairment in MINOCA patients in comparison to those with MI with obstructive coronary artery disease (MICAD) and non-obstructive stable coronary artery disease (SCAD). Methods. The study group comprised 40 patients (29 men, mean age 62.9 ± 10.7 years). 28 patients were admitted to the hospital due to the acute coronary syndrome. At admission all patients underwent invasive coronary angiography (ICA) and cardiac biomarkers – Creatine phosphokinase-MB (CPK-MB) and Troponin I (TnI) measurement. Two groups of patients were created based on ICA results: 1) MINOCA: with coronary artery stenosis &amp;lt;50%, n = 11; 2) MICAD: with coronary artery stenosis ≥50%, n = 17. SCAD patients group without obstructive atherosclerosis was retrospectively selected from the hospital database. All patients underwent dynamic SPECT on Cadmium-Zinc-Telluride (CZT) gamma camera with the assessment of semi-quantitative indexes of myocardial perfusion (SSS, SRS, SDS) and quantitative parameters (rest MBF (rMBF), stress MBF (sMBF) and MFR). Results. After 24 hours cardiospecific biomarkers levels in MINOCA group were significantly (p &amp;lt; 0.05) lower compared to MICAD group: CPK-MB 21.5 (13.7;45.0) vs. 94.4 (53.1;217.0) U/L; TnI 0.5 (0.1;3.3) vs. 9.8 (2.0;23.0) ng/ml. Standard myocardial perfusion indexes differed significantly (p &amp;lt; 0.05) among all three groups (except SDS between the first and second groups): MINOCA: SSS 5.0 (3.0;6.0), SDS 2.0 (1.0;3.0); MICAD: SSS 9.0 (5.0;13.0), SDS 3.0 (2,0;5.0); SCAD: SSS 1.5 (0.5;2.0), SDS 0.0 (0.0;2.0). Moreover, sMBF and MFR differed significantly in all three groups of patients: MINOCA: sMBF 1.2 (0.8;1.7) ml/min/g, MFR 2.0 (1.2;2.4); MICAD: sMBF 0.7 (0.6;1.0) ml/min/g, MFR 1.2 (1.1;1.5); control group: sMBF 2.2 (2.1;2.3) ml/min/g, MFR 2.6 (2.5;2.8). In 7/11 (64%) of MINOCA patients the value of sMBF was ≤1.5 ml/min/g. In the MICAD group 16/17 (94%) had sMBF ≤1.5 ml/min/g and all SCAD patients had sMBF &amp;gt;1.5 ml/min/g. In 4/11 (36%) of MINOCA patients MFR values were less than 2; in MICAD group MFR &amp;lt; 2 was observed in 15/17 (88%) patients. Conclusion. MINOCA patients have more severe myocardial perfusion abnormalities, lower MBF and MFR compared to those with stable CAD. It means that MINOCA patients may have other reasons for reduced myocardial blood flow, such as endothelial dysfunction, thrombophilia, etc., despite the absence of obstructive coronary artery lesion. Further studies are needed to assess added diagnostic and prognostic value of CZT SPECT derived myocardial flow indexes in MINOCA patients.

Impact of Time Post-Heart Transplant on Myocardial Flow Reserve and Outcomes

Myocardial flow reserve (MFR) compares hyperemic to resting myocardial blood flow to evaluate the effects of coronary stenosis or microvascular disease on myocardial blood flow (MBF). Positron emission tomography (PET) is the most accurate noninvasive modality for assessing MBF and diagnosing coronary disease. Impaired MFR by PET is also predictive of adverse events, including mortality, for both atherosclerosis and cardiac allograft vasculopathy (CAV). Prior studies assessing MFR in CAV included patients an average of 10 years post heart transplant (HT). We sought to assess whether the prognostic effect of MFR was consistent both early and late after HT. From 2016-2017 206 patients underwent rest/stress 13N ammonia PET with CT attenuation correction. The cohort was divided into quartiles: 0-4y, 4-7y, 7-11y, >11y post-HT. MFR data were compared over time. 181 patients (Exclusions: 3 technically limited, 22 had high rest flows) were enrolled in the study. Overall MFR values (median, IQR) were consistent among the first three quartiles, but were lower for the >11y quartile (2.16 [1.82-2.66], 2.11 [1.75-2.77], 2.19 [1.82-2.77], 2.01 [1.52-2.76] p<0.001). MFR was less than 1.96 in 37.6% of the overall cohort and was similar across the quartiles (29.8% vs 40% vs 34.8% vs 46.5%, p=0.4). MFR was associated with an increased risk of the combined endpoint of death, retransplantation, or CV hospitalization (HR 7.58, p<0.001) in the entire cohort during a median follow-up of 2.3y. When stratified by the median time post-HT, MFR remained predictive of adverse events. Early post-HT there was a 3.84 fold increased risk of combined endpoint for those with a MFR<1.96 (Figure, p<0.05). This effect was significantly greater during the late period (HR 26.3, p<0.001). Decreased MFR is associated with an increased risk of death, retransplantation, or cardiovascular hospitalization following HT. This effect is seen both early and late after transplant, with a dramatically increased risk after 7 years.

15-O-water myocardial flow reserve PET and CT angiography by full hybrid PET/CT as a potential alternative to invasive angiography

Combined myocardial flow reserve (MFR) by PET and CT coronary angiography (CTA) is a promising tool for assessment of coronary artery disease. Prior analyses of MFR/CTA has been performed as side-by-side interpretation, not as volume rendered, full hybrid analysis, with fused MFR/CTA. We aimed to: (i) establish a method for full hybrid analysis of MFR/CTA, (ii) validate the inter- and intra-observer reproducibility of MFR values, and (iii) determine the diagnostic value of side-by-side versus full hybrid MFR/CTA with 15-O-water PET. Forty-four outpatients scheduled for invasive coronary angiography (ICA) were enrolled prospectively. All underwent rest/stress 15-O-water PET/CTA with ICA as reference. Within two observers of different experience, the Pearson r at global and territorial level exceeded 0.953 for rest, stress, and MFR values, as determined by Carimas software. Within and between observers, the mean differences between rest, stress, and MFR values were close to zero and the confidence intervals for 95% limits of agreement were narrow. The diagnostic performance of full hybrid PET/CTA did not outperform the side-by-side approach, but performed better than MFR without CTA at vessel level: specificity 93% (95% confidence limits: 89-97%) versus 76% (64-88%), p = 0.0004; positive predictive value 71% (55-86%) versus 51% (37-65%), p = 0.0001; accuracy 90% (84-95%) versus 77% (69-84%), p = 0.0009. MFR showed high reproducibility within and between observers of different experience. The full hybrid model was not superior to side-by-side interpretation of MFR/CTA, but proved better than MFR alone at vessel level with regard to specificity, positive predictive value, and accuracy.

Comparison of two software systems for quantification of myocardial blood flow in patients with hypertrophic cardiomyopathy

BackgorundQuantification of myocardial blood flow (MBF) by positron emission tomography (PET) is important for investigation of angina in hypertrophic cardiomyopathy (HCM). Several software programs exist for MBF quantification, but they have been mostly evaluated in patients (with normal cardiac geometry), referred for evaluation of coronary artery disease (CAD). Software performance has not been evaluated in HCM patients who frequently have hyperdynamic LV function, LV outflow tract (LVOT) obstruction, small LV cavity size, and variation in the degree/location of LV hypertrophy. AimWe compared results of MBF obtained using PMod, which permits manual segmentation, to those obtained by FDA-approved QPET software which has an automated segmentation algorithm. Methods13N-ammonia PET perfusion data were acquired in list mode at rest and during pharmacologic vasodilation, in 76 HCM patients and 10 non-HCM patients referred for evaluation of CAD (CAD group.) Data were resampled to create static, ECG-gated and 36-frame-dynamic images. Myocardial flow reserve (MFR) and MBF (in ml/min/g) were calculated using QPET and PMod softwares. ResultsAll HCM patients had asymmetric septal hypertrophy, and 50% had evidence of LVOT obstruction, whereas non-HCM patients (CAD group) had normal wall thickness and ejection fraction. PMod yielded significantly higher values for global and regional stress-MBF and MFR than for QPET in HCM. Reasonably fair correlation was observed for global rest-MBF, stress-MBF, and MFR using these two softwares (rest-MBF: r = 0.78; stress-MBF: r = 0.66.; MFR: r = 0.7) in HCM patients. Agreement between global MBF and MFR values improved when HCM patients with high spillover fractions (> 0.65) were excluded from the analysis (rest-MBF: r = 0.84; stress-MBF: r = 0.72; MFR: r = 0.8.) Regionally, the highest agreement between PMod and QPET was observed in the LAD territory (rest-MBF: r = 0.82, Stress-MBF: r = 0.68) where spillover fraction was the lowest. Unlike HCM patients, the non-HCM patients (CAD group) demonstrated excellent agreement in MBF/MFR values, obtained by the two softwares, when patients with high spillover fractions were excluded (rest-MBF: r = 0.95; stress-MBF: r = 0.92; MFR: r = 0.95). ConclusionsAnatomic characteristics specific to HCM hearts contribute to lower correlations between MBF/MFR values obtained by PMod and QPET, compared with non-HCM patients. These differences indicate that PMod and QPET cannot be used interchangeably for MBF/MFR analyses in HCM patients.