Hyperemic Myocardial Blood Flow Research Articles

The association of coronary lumen volume to left ventricle mass ratio with myocardial blood flow and fractional flow reserve

BackgroundA diminished coronary lumen volume to left ventricle mass ratio (V/M) derived from coronary computed tomography angiography (CCTA) has been proposed as factor contributing to impaired myocardial blood flow (MBF) even in the absence of obstructive disease on invasive coronary angiography (ICA). MethodsPatients underwent CCTA, and positron emission tomography (PET) prior to ICA. Matched global V/M, global, and vessel specific hyperaemic MBF (hMBF), coronary flow reserve (CFR), and, FFR were available for 431 vessels in 152 patients. The median V/M (20.71 mm3/g) was used to divide the population into patients with either a low V/M or a high V/M. ResultsOverall, a higher percentage of vessels with an abnormal hMBF and FFR (34% vs. 19%, p = 0.009 and 20% vs. 9%, p = 0.004), as well as a lower FFR (0.93 [interquartile range: 0.85–0.97] vs. 0.95 [0.89–0.98], p = 0.016) values were observed in the low V/M group. V/M was weakly associated with vessel specific hMBF (R = 0.148, p = 0.027), and FFR (R = 0.156, p < 0.001). Among vessels with non-obstructive CAD on ICA (361 vessels), no association between V/M and vessel specific hMBF nor CFR was noted. However, in the absence of obstructive CAD, V/M was associated with (R = 0.081, p = 0.027), and independently predictive for FFR (p = 0.047). ConclusionOverall, an abnormal vessel specific hMBF and FFR were more prevalent in patients with a low V/M compared to those with a high V/M. Furthermore, V/M was weakly associated with vessel specific hMBF and FFR. In the absence of obstructive CAD on ICA, V/M was weakly associated with notwithstanding independently predictive for FFR.

P599Relationship between coronary artery calcium and hyperaemic myocardial blood flow in asymptomatic adults with type 2 diabetes

P599Relationship between coronary artery calcium and hyperaemic myocardial blood flow in asymptomatic adults with type 2 diabetes

Myocardial Blood Flow and Coronary Flow Reserve During 3 Years Following Bioresorbable Vascular Scaffold Versus Metallic Drug-Eluting Stent Implantation: The VANISH Trial

ObjectivesThe randomized clinical VANISH (Impact of Vascular Reparative Therapy on Vasomotor Function and Myocardial Perfusion: A Randomized [15O]H2O PET/CT Study) trial was conducted to assess quantitative myocardial blood flow (MBF) during resting, hyperemia, and cold pressor testing (CPT) with positron emission tomographic perfusion imaging after the implantation of a bioresorbable everolimus-eluting scaffold compared with a drug-eluting stent. BackgroundLong-term resorption of the bioresorbable everolimus-eluting scaffold reinstates normal vessel geometry, allowing natural regeneration of the newly formed endothelium with revival of vasomotor function. MethodsSixty patients (18 to 65 years of age) with single-vessel disease and type A or B1 lesions were randomized in a 1-to-1 fashion. Approximately 1 month, 1 year, and 3 years after device implantation, patients underwent [15O]H2O cardiac positron emission tomography. The primary endpoint was the interaction of device type and evolution over time of hyperemic MBF, coronary flow reserve, or CPT reserve. At 3-year follow-up, control invasive coronary angiography with optical coherence tomography was performed. ResultsFifty-nine (98%), 56 (93%), and 51 (85%) patients successfully completed 1-month, 1-year, and 3-year follow-up positron emission tomography, respectively, and no culprit vessel events were registered during follow-up time. The primary study endpoint (i.e., interaction between device type and time) was nonsignificant for hyperemic MBF, CPT reserve, and coronary flow reserve (p > 0.05 for all). In all patients, hyperemic MBF decreased from 1 to 3 years (p = 0.02), while coronary flow reserve was lower at 3-year follow-up compared with 1-month and 1-year follow-up (p = 0.03 for both). After 3 years, percentage area stenosis measured with optical coherence tomography was higher within the bioresorbable everolimus-eluting scaffold compared with the drug-eluting stent (p = 0.03). ConclusionsThe hypothesized beneficial effects of scaffold resorption did not translate to improved MBF during maximal hyperemia or endothelium-dependent vasodilation by CPT.

Quantification of PET Myocardial Blood Flow.

The aim of this review is to provide an update on quantification of myocardial blood flow (MBF) with positron emission tomography (PET) imaging. Technical and clinical aspects of flow quantification with PET are reviewed. The diagnostic and prognostic values of myocardial flow quantification have been established in numerous studies and in various populations. MBF quantification has also shown itself to be particularly useful in the assessment of coronary microvascular dysfunction and in evaluation of cardiac allograft vasculopathy. Overall, myocardial flow reserve (MFR) and hyperemic MBF can lead to improved risk stratification by providing information complementary to that of other markers of disease severity, such as fractional flow reserve. Flow quantification enhances MPI's ability to detect both significant epicardial disease and microvascular dysfunction. With recent technological and methodological advances, flow quantification with PET is no longer restricted to cyclotron-equipped academic centers.

Coronary vascular function in patients with resistant hypertension and normal myocardial perfusion: a propensity score analysis.

Impaired myocardial perfusion reserve (MPR) may occur earlier than coronary atherosclerosis and it may be an early manifestation of developing coronary artery disease (CAD) in patients with resistant hypertension (RH). We evaluated the relationship between RH and MPR in patients with systemic arterial hypertension after balancing for coronary risk factors. We studied 360 subjects without overt CAD and normal myocardial perfusion at stress-rest 82Rb positron emission tomography/computed tomography. To account for differences in baseline characteristics between patients with resistant and controlled hypertension, we created a propensity score-matched cohort considering clinical variables and coronary risk factors. Before matching, patients with RH were significantly older, had higher prevalence of male gender and hypercholesterolaemia, and showed significantly lower global hyperaemic myocardial blood flow (MBF) and MPR compared with those with controlled hypertension, while baseline MBF and coronary artery calcium (CAC) content were similar in both groups. After matching, there were no significant differences in clinical variables and coronary risk factors between patients with resistant and controlled hypertension, but patients with RH still had lower hyperaemic MBF and MPR (both P < 0.001). At univariable and multivariable linear regression analyses, age, RH, and CAC resulted significant predictors of lower MPR values (all P < 0.05). After balancing clinical characteristic by propensity score analysis, patients with RH had a blunted hyperaemic MBF and MPR compared with patients with controlled hypertension. The identification of impaired MPR could help to identify early structural alterations of the arterial walls in patients with RH.

Comparison of maximal hyperemic myocardial blood flow response between regadenoson and adenosine: A quantitative positron emission tomography 13n-ammonia study

Comparison of maximal hyperemic myocardial blood flow response between regadenoson and adenosine: A quantitative positron emission tomography 13n-ammonia study

Impact of individualized segmentation on diagnostic performance of quantitative positron emission tomography for haemodynamically significant coronary artery disease.

Despite high variability in coronary anatomy, quantitative positron emission tomography (PET) perfusion in coronary territories is traditionally calculated according to the American Heart Association (AHA) 17-segments model. This study aimed to assess the impact of individualized segmentation of myocardial segments on the diagnostic accuracy of hyperaemic myocardial blood flow (MBF) values for haemodynamically significant coronary artery disease (CAD). Patients with suspected CAD (n = 204) underwent coronary computed tomography angiography (CCTA) and [15O]H2O PET followed by invasive coronary angiography with fractional flow reserve assessment of all major coronary arteries. Hyperaemic MBF per vascular territory was calculated using both standard segmentation according to the AHA model and individualized segmentation, in which CCTA was used to assign coronary arteries to PET perfusion territories. In 122 (59.8%) patients, one or more segments were redistributed after individualized segmentation. No differences in mean MBF values were seen between segmentation methods, except for a minor difference in hyperaemic MBF in the LCX territory (P = 0.001). These minor changes resulted in discordant PET-defined haemodynamically significant CAD between the two methods in only 5 (0.8%) vessels. The diagnostic value for detecting haemodynamically significant CAD did not differ between individualized and standard segmentation, with area under the curves of 0.79 and 0.78, respectively (P = 0.34). Individualized segmentation using CCTA-derived coronary anatomy led to redistribution of standard myocardial segments in 60% of patients. However, this had little impact on [15O]H2O PET MBF values and diagnostic value for detecting haemodynamically significant CAD did not change. Therefore, clinical impact of individualized segmentation seems limited.

Abstract 16649: Recovery of Myocardial Perfusion After Percutaneous Coronary Intervention of Chronic Total Occlusions is Comparable to Non-Occlusive Lesions

Background: The benefits of chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI) are being questioned. The aim of this study was to assess the effects of CTO PCI on absolute myocardial perfusion, as compared to PCI of hemodynamically significant non-occlusive lesions. Methods: Consecutive patients with a preserved left ventricular ejection fraction (≥50%) and a CTO or non-CTO lesion, in whom [ 15 O]H 2 O positron emission tomography was performed prior and after successful PCI, were included. Change in quantitative (hyperemic) myocardial blood flow (MBF), coronary flow reserve (CFR) and perfusion defect size (in myocardial segments) were compared between CTOs and non-occlusive lesions. Results: Ninety-two patients with a CTO and 31 patients with a non-occlusive lesion were included. CTOs induced larger perfusion defect sizes (4.51±1.69 vs. 3.23±2.38 segments, p&lt;0.01) with lower hyperemic MBF (1.30±0.37 vs. 1.58±0.62 mL·min -1 ·g -1 , p&lt;0.01) and similarly impaired CFR (1.66±0.75 vs. 1.89±0.77, p=0.17) compared with non-occlusive lesions. After PCI both hyperemic MBF and CFR increased similarly between groups (p=0.57 and p=0.35) to normal ranges with higher hyperemic MBF values in non-CTO compared to CTO (2.89±0.94 vs. 2.48±0.73 mL·min -1 ·g -1 , p=0.03). Perfusion defect sizes decreased similarly after CTO PCI and non-CTO PCI (p=0.14), leading to small residual defect sizes in both groups (1.15±1.44 vs. 0.61±1.45 segments, p=0.054). Conclusions: Percutaneous revascularization of CTOs improves absolute myocardial perfusion similarly to PCI of hemodynamically significant non-occlusive lesions, leading to satisfying results. Myocardial perfusion findings are less favorable in patients with a CTO before and after PCI, suggesting a more advanced stage of coronary artery disease.

Diagnostic value of longitudinal flow gradient for the presence of haemodynamically significant coronary artery disease.

The longitudinal myocardial blood flow (MBF) gradient derived from positron emission tomography (PET) has been proposed as an emerging non-invasive index of haemodynamically significant coronary artery disease (CAD). This study aimed to investigate the diagnostic value of longitudinal MBF gradient for the presence of haemodynamically significant CAD. A total of 204 patients (603 vessels) with suspected CAD underwent [15O]H2O PET followed by invasive coronary angiography with fractional flow reserve (FFR) of all major coronary arteries. Longitudinal base-to-apex MBF gradients were assessed by two methods, using MBF in apical and mid (Method 1) or in apical and basal (Method 2) myocardial segments to calculate the gradient. The hyperaemic longitudinal MBF gradient was only weakly correlated with FFR (Method 1: r = 0.12, P = 0.02; Method 2: r = 0.22, P < 0.001). The hyperaemic longitudinal MBF gradient (by both methods), had lower diagnostic value when compared with hyperaemic MBF for the presence of haemodynamically significant CAD, defined as an FFR ≤ 0.80. No significant correlations between longitudinal MBF gradients and FFR were noted in proximal lesions, whereas longitudinal MBF gradients and FFR were significantly correlated in non-proximal lesions (r = 0.57, P < 0.001). PET measured longitudinal flow parameters had lower diagnostic value when compared with hyperaemic MBF for the presence of haemodynamically significant CAD. Since lesion location was found to affect the correlation of PET measured longitudinal flow parameters and FFR, presence of a longitudinal flow gradient may be partly caused by normalization to a relatively normal perfused areas.

Diagnostic value of quantitative coronary flow reserve and myocardial blood flow estimated by dynamic 320 MDCT scanning in patients with obstructive coronary artery disease.

We have developed the method for dynamic 320-row multidetector computed tomography (MDCT)-derived quantitative coronary flow reserve (CFRCT) and hyperemic myocardial blood flow (MBFCT). We evaluated diagnostic value of CFRCT and hyperemic MBFCT for detecting obstructive coronary artery disease (CAD) in per-patient and per-vessel analysis, and their relations with the severity of CAD burden.Adenosine stressed and rest dynamic myocardial perfusion MDCT were prospectively performed in patients with known or suspected CAD. Per-patient and per-vessel MBFCT were estimated from dynamic perfusion images in rest and hyperemic phases, and per-patient and per-vessel CFRCT were calculated from the ratio of rest and hyperemic MBFCT. Degree of stenosis was evaluated by coronary CT angiography (CTA) and invasive coronary angiography (ICA). Obstructive stenosis was defined as ≥70% stenosis in ICA. CAD burden with MDCT was calculated by logarithm transformed coronary artery calcium (CAC) score and the CTA-adapted Leaman risk score (CT-LeSc). A logistic regression analysis was used to measure the receiver-operating characteristic curve and corresponding area under the curve (AUC) for the detection of obstructive CAD.Twenty-seven patients and 81 vessels were eligible for this study. Sixteen patients had obstructive CAD, and 31 vessels had obstructive stenosis. Using an optimal cutoff, the CFRCT and hyperemic MBFCT had the moderate diagnostic values in per-patient (AUC = 0.89 and 0.86, respectively) and per-vessel (AUC = 0.79 and 0.76, respectively). Per-patient CFRCT and hyperemic MBFCT exhibited a moderate inverse correlation with CAC score and the CT-LeSc.Per-patient and per-vessel CFRCT as well as hyperemic MBFCT had moderate diagnostic value for detecting obstructive CAD. These per-patient values exhibited a moderate inverse correlation with CAD burden. CFRCT and hyperemic MBFCT might add quantitative functional information for evaluating patients with CAD.

Absolute Myocardial Blood Flow After Elective Percutaneous Coronary Intervention Evaluated on Phase-Contrast Cine Cardiovascular Magnetic Resonance Imaging.

Few studies have documented changes in myocardial blood flow (MBF) after percutaneous coronary intervention (PCI). Phase-contrast cine cardiovascular MRI (PC-CCMR) of the coronary sinus (CS) is a promising approach to quantify MBF. The aim of this study was to quantify CS flow (CSF) on PC-CCMR as a measure of volumetric MBF before and after elective PCI.Methods and Results:We prospectively studied 34 patients with stable angina undergoing elective PCI for a single de novo lesion. Breath-hold PC-CCMR of CS was acquired to assess CSF and coronary flow reserve (CFR) at rest and during maximum hyperemia both before and after PCI (median, 3 days before PCI and 10 days after PCI, respectively). In total, hyperemic CSF increased significantly after PCI (before PCI, median, 2.3 mL/min/g [IQR, 1.5-3.2 mL/min/g] after PCI, 3.0 [1.8-3.7] mL/min/g), although 13 patients (38.2%) had a decrease despite successful PCI and fractional flow reserve (FFR) improvement. Global CFR also significantly increased from a median of 2.5 (IQR, 1.5-3.5) to 3.4 (IQR, 2.1-4.2), whereas 12 patients had decreased CFR after PCI. Pre-PCI hyperemic CSF was the only independent factor of change in CSF following PCI. Serial PC-CCMR of CS as a measure of change in absolute MBF is feasible. Uncomplicated PCI does not necessarily increase hyperemic global MBF, despite regional FFR improvement.

Effect of Plaque Burden and Morphology on Myocardial Blood Flow and Fractional Flow Reserve

BackgroundAtherosclerotic plaque characteristics may affect downstream myocardial perfusion, as well as coronary lesion severity. ObjectivesThis study sought to evaluate the association between quantitative plaque burden and plaque morphology obtained using coronary computed tomography angiography (CTA) and quantitative myocardial perfusion obtained using [15O]H2O positron emission tomography (PET), as well as fractional flow reserve (FFR) derived invasively. MethodsTwo hundred eight patients (63% men; age 58 ± 8.7 years) with suspected coronary artery disease were prospectively included. All patients underwent 256-slice coronary CTA, [15O]H2O PET, and invasive FFR measurements. Coronary CTA-derived plaque burden and morphology were assessed using commercially available software and compared with PET perfusion and FFR. ResultsAtherosclerotic plaques were present in 179 patients (86%) and 415 of 610 (68%) evaluable coronary arteries. On a per-vessel basis, traditional coronary plaque burden indexes, such as plaque length and volume, minimal lumen area, and stenosis percentage, were significantly associated with impaired hyperemic myocardial blood flow (MBF) and FFR. In addition, morphological features, such as partially calcified plaques, positive remodeling (PR), and low attenuation plaque, displayed a negative impact on hyperemic MBF and FFR. Multivariable analysis revealed that the morphological feature of PR was independently related to impaired hyperemic MBF as well as an unfavorable FFR (p = 0.004 and p = 0.007, respectively), next to stenosis percentage (p = 0.001 and p < 0.001, respectively) and noncalcified plaque volume (p < 0.001 and p = 0.010, respectively). ConclusionsPR and noncalcified plaque volume are associated with detrimental downstream hyperemic myocardial perfusion and FFR, independent of lesion severity.

Combined evaluation of regional coronary artery calcium and myocardial perfusion by 82Rb PET/CT in the identification of obstructive coronary artery disease.

Cardiac imaging with PET/CT allows measurement of coronary artery calcium (CAC), myocardial perfusion and coronary vascular function. We investigated whether the combined assessment of regional CAC score, ischemic total perfusion deficit (ITPD) and quantitative coronary vascular function would further improve the diagnostic accuracy of PET/CT in predicting obstructive coronary artery disease (CAD). We analyzed 113 patients with suspected CAD referred to 82Rb PET/CT myocardial perfusion imaging with available coronary angiographic data. Obstructive CAD was defined as ≥75% stenosis. The receiver operating characteristic area under curve (AUC) was applied to evaluate the ability of CAC score, ITPD, hyperemic myocardial blood flow (MBF) and coronary flow reserve (CFR) to identify CAD. Vessels with obstructive CAD (71 vessels) had higher ITPD (4.6 ± 6.2 vs. 0.6 ± 1.3) and lower hyperemic MBF (1.01 ± 0.5 vs. 1.75 ± 0.6ml/min/g) and CFR (1.56 ± 0.6 vs. 2.38 ± 0.7; all p < 0.001) than those without. In prediction of per-vessel CAD, the AUCs for the models including CAC/ITPD/hyperemic MBF (0.869) and CAC/ITPD/CFR (0.875) were higher (both p < 0.01) than for the model including CAC/ITPD (0.790). Compared with CAC/ITPD, continuous net reclassification improvement was 0.69 (95% bootstrap confidence interval, CI, 0.365-1.088) for the CAC/ITPD/hyperemic MBF model and 0.99 (95% bootstrap CI 0.64-1.26) for the CAC/ITPD/CFR model. Hyperemic MBF and CFR provide incremental information about the presence of CAD over CAC score and perfusion imaging parameters. The combined use of CAC, myocardial perfusion imaging and quantitative coronary vascular function in may help predict more accurately the presence of obstructive CAD.

Diagnostic Value of Transluminal Attenuation Gradient for the Presence of Ischemia as Defined by Fractional Flow Reserve and Quantitative Positron Emission Tomography

ObjectivesThe aim of this study was to investigate the incremental diagnostic value of transluminal attenuation gradient (TAG), TAG with corrected contrast opacification (TAG-CCO), and transluminal diameter gradient (TDG) over coronary computed tomography angiography (CTA)–derived diameter stenosis alone for the identification of ischemia as defined by both the invasive reference standard fractional flow reserve (FFR) and the noninvasive reference standard quantitative positron emission tomography (PET). BackgroundIn addition to anatomic information obtained by coronary CTA, several functional CT parameters have been proposed to identify hemodynamically significant lesions more accurately, such as TAG, TAG-CCO, and more recently TDG. However, clinical validation studies have reported conflicting results, and a recent study has suggested that TAG may be affected by changes in vessel diameter. MethodsPatients with suspected coronary artery disease underwent coronary CTA and [15O]H2O PET followed by invasive coronary angiography with FFR of all major coronary arteries. TAG, TAG-CCO, and TDG were assessed, and the incremental diagnostic value of these parameters over coronary CTA–derived diameter stenosis alone for ischemia as defined by PET (hyperemic myocardial blood flow ≤2.30 ml/min/g) and FFR (≤0.80) was determined. ResultsA total of 557 (91.9%) coronary arteries of 201 patients were included for analysis. TAG, TAG-CCO, and TDG did not discriminate between vessels with or without ischemia as defined by either PET or FFR. Furthermore, these parameters did not have incremental diagnostic accuracy over coronary CTA alone for the presence of ischemia as defined by PET and FFR. There was a significant correlation between TDG and TAG (r = 0.47; p < 0.001) and between TDG and TAG-CCO (r = 0.37; p < 0.001). ConclusionsTAG, TAG-CCO, and TDG do not provide incremental diagnostic value over coronary CTA alone for the presence of ischemia as defined by [15O]H2O PET and/or FFR. The lack of diagnostic value of contrast enhancement–based flow estimations appears related to coronary luminal dimension variability.

Similarity and Difference of Resting Distal to Aortic Coronary Pressure and Instantaneous Wave-Free Ratio

BackgroundInstantaneous wave-free ratio (iFR) has been used in clinical practice to identify functionally significant stenosis and to guide treatment strategy. However, there are limited clinical data regarding another resting pressure-derived index, resting distal to aortic coronary pressure (Pd/Pa), and similarities and differences between resting Pd/Pa and iFR. ObjectivesThe authors investigated the changes in resting Pd/Pa and iFR according to anatomic and hemodynamic stenosis severity and their prognostic implications. MethodsFrom the 3V FFR-FRIENDS (Clinical Implication of 3-vessel Fractional Flow Reserve) and the IRIS-FFR (Study of the Natural History of FFR Guided Percutaneous Coronary Intervention) studies, 1,024 vessels (n = 435) with available pre-intervention resting Pd/Pa and iFR were used to explore the changes in resting physiological indices according to percent diameter stenosis. Among 115 patients who underwent 13N-ammonia positron emission tomography, the changes in those indices according to basal and hyperemic stenosis resistance and absolute hyperemic myocardial blood flow were compared. The association between physiological indices and the risk of 2-year major adverse cardiac events (MACE) (a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization) were analyzed among 375 deferred patients. ResultsThere was a significant linear correlation between resting Pd/Pa and iFR (R = 0.970; p < 0.001, iFR = 1.370 × resting Pd/Pa − 0.370). Both resting Pd/Pa and iFR changed significantly according to percent diameter stenosis, basal and hyperemic stenosis resistance, and hyperemic absolute myocardial blood flow (all p values <0.001). Percent difference of iFR according to the increase in anatomic and hemodynamic severity was higher than that of resting Pd/Pa. Both resting Pd/Pa and iFR showed a significant association with the risk of 2-year MACE (resting Pd/Pa hazard ratio [per 0.10 increase]: 0.480; 95% confidence interval: 0.250 to 0.923; p = 0.027; iFR hazard ratio [per 0.1 increase]: 0.586; 95% confidence interval: 0.373 to 0.919; p = 0.020) in deferred patients. However, the difference between the upper- and lower-bound estimated MACE rates according to the approximate measurement variability of each index was significantly higher with resting Pd/Pa compared with iFR (resting Pd/Pa 3.85 ± 4.00% and iFR 3.27 ± 3.39%; p < 0.001). ConclusionsBoth resting Pd/Pa and iFR showed similar associations with anatomic and hemodynamic stenosis severity and the risk of MACE. However, iFR was more sensitive to the difference in stenosis severity and showed a lower maximum difference in estimated MACE risk influenced by the measurement variability compared with resting Pd/Pa. (Clinical Implication of 3-Vessel Fractional Flow Reserve [3V FFR-FRIENDS]; NCT01621438; and Study of the Natural History of FFR Guided Percutaneous Coronary Intervention [IRIS-FFR]; NCT01366404)

Clinical Usefulness of Coronary Flow Reserve Ratio for the Detection of Significant Coronary Artery Disease on &lt;sup&gt;13&lt;/sup&gt;N-Ammonia Positron Emission Tomography

This study aimed to evaluate the diagnostic performance of coronary flow reserve (CFR), hyperemic myocardial blood flow (hMBF), and CFR ratio for detecting significant coronary artery disease (CAD) on 13N-ammonia positron emission tomography (PET).Methods and Results:We analyzed 63 patients (mean age, 71±9 years; 43 males) with suspected CAD who underwent both pharmacological stress/rest 13N-ammonia PET and coronary angiography. CFR and hMBF for PET were calculated automatically using quantitative PET software, and the CFR ratio was defined as the ratio of per-vessel CFR to maximum CFR in a standard 17-segment model. We compared the diagnostic performance among the 3 quantitative values. In the per-vessel analysis, 55 vessels were diagnosed as significant CAD (≥70% stenosis and/or fraction flow reserve ≤0.8). CFR, hMBF, and CFR ratio of significant CAD were significantly lower than for non-significant CAD (1.85±0.69 vs. 2.38±0.69; P<0.01, 1.67±0.54 vs. 2.19±0.52 mL·min-1·g-1; P<0.01, and 0.66±0.15 vs. 0.82±0.09; P<0.01, respectively). In the receiver-operating characteristic curve analysis, CFR, hMBF, and CFR ratio had areas under the curve of 0.71, 0.75, and 0.85 respectively, and the CFR ratio was significantly higher than CFR and hMBF (P<0.05). The sensitivity, specificity, and accuracy of the CFR ratio with an optimal cutoff value of 0.75 were 75%, 85%, and 82%, respectively. Clinically, the CFR ratio in 13N-ammonia PET was more effective in detecting significant CAD.

Single-scan rest/stress imaging with 99mTc-Sestamibi and cadmium zinc telluride-based SPECT for hyperemic flow quantification: A feasibility study evaluated with cardiac magnetic resonance imaging.

IntroductionWe aimed to evaluate whether the hyperemic myocardial blood flow (MBF) can be estimated using cadmium zinc telluride (CZT)-based single-photon emission computed tomography (SPECT) cameras with a single, rapid rest/stress dynamic scan. Dynamic contrast-enhanced (DCE) cardiac magnetic resonance imaging (MRI) was used as a reference modality for flow measurement.Materials and methodsThe proposed protocol included both the rest and stress acquisitions within a 24-min scan. Patients were first injected with 99mTc-Sestamibi at the resting state. Sixty minutes after the first injection, the subject was positioned via scintigraphy, after which the list-mode data acquisition was initiated and continued for 24 minutes. Five minutes after data acquisition was initiated, a stressed state was induced via dipyridamole infusion, after which a second dose of 99mTc-Sestamibi was injected. Dynamic SPECT images were reconstructed for all subjects, who also underwent T1-weighted cardiac DCE-MRI performed on days other than those of the SPECT studies. MBF values were estimated for the rest and stress MRI studies, and for the stress portion of the SPECT study. The SPECT-measured hyperemic MBF was compared with the MR-measured hyperemic MBF and coronary flow reserve (CFR), based on the regions of interest.ResultsA total of 30 subjects were included in this study. The hyperemic MBF estimated from SPECT showed a strong correlation with the MR-measured hyperemic MBF (r2 = 0.76) and a modest correlation with the MR-measured CFR (r2 = 0.56). Using MR-measured CFR <1.3 as a cutoff for coronary stenosis, we found that the SPECT-measured hyperemic MBF served as a useful clinical index with 94% sensitivity, 90% specificity, and 93% accuracy.ConclusionsHyperemic MBF can be measured with a rapid, single-scan rest/stress study with CZT-based SPECT cameras.

Noninvasive PET quantitative myocardial blood flow with regadenoson for assessing cardiac allograft vasculopathy in orthotopic heart transplantation patients

BackgroundRisk stratification and early detection of cardiac allograft vasculopathy (CAV) is essential in orthotopic heart transplantation (OHT) patients. This study assesses the changes in myocardial blood flow (MBF) noninvasively in OHT patients using quantitative cardiac PET with regadenoson. MethodsTwelve patients (Group 1) (8 males, 4 females, mean age 55 ± 7 years) with no history of post OHT myocardial ischemia were enrolled 5.4 ± 2.0 years after OHT. Fifteen patients (Group 2) (9 males, 6 females, mean age 71 ± 9 years) with intermediate pretest probability but not documented evidence for coronary artery disease (CAD) were also included to serve as control. Global and regional MBFs were assessed using dynamic 13N-NH3 PET at rest and during regadenoson-induced hyperemia. The coronary flow reserve (CFR) was also calculated as the ratio of hyperemic to resting MBF. ResultsMean regadenoson-induced rate-pressure products were similar in both groups, while there was an increase in resting rate-pressure product in Group 1 patients. Both mean and median values of resting MBF were higher in Group 1 than Group 2 patients (1.33 ± 0.31 and 1.01 ± 0.21 mL/min/g for Groups 1 and 2, respectively, P < .001), while mean hyperemic MBF values were similar in both Groups (2.68 ± 0.84 and 2.64 ± 0.94 mL/min/g, P = NS) but median hyperemic MBF values were lower in Group 1 than Group 2 patients (2.0 vs. 2.60 mL/min/g, P = .018). Both mean and median CFR values demonstrated a significant reduction for Group 1 compared to Group 2 patients (2.07 ± 0.74 vs 2.63 ± 0.48, P = .025). ConclusionsThis study suggests that the MBF in OHT patients may be abnormal at resting state with diminished CFR. This hints that the epicardial and microvascular coronary subsystem may be exacerbated after OHT leading to the gradual progression of CAV.

Positron Emission Tomography-Determined Hyperemic Flow, Myocardial Flow Reserve, and Flow Gradient-Quo Vadis?

Positron emission tomography/computed tomography (PET/CT) applied with positron-emitting flow tracers such as 13N-ammonia and 82Rubidium enables the quantification of both myocardial perfusion and myocardial blood flow (MBF) in milliliters per gram per minute for coronary artery disease (CAD) detection and characterization. The detection of a regional myocardial perfusion defect during vasomotor stress commonly identifies the culprit lesion or most severe epicardial narrowing, whereas adding regional hyperemic MBFs, myocardial flow reserve (MFR), and/or longitudinal flow decrease may also signify less severe but flow-limiting stenosis in multivessel CAD. The addition of regional hyperemic flow parameters, therefore, may afford a comprehensive identification and characterization of flow-limiting effects of multivessel CAD. The non-specific origin of decreases in hyperemic MBFs and MFR, however, prompts an evaluation and interpretation of regional flow in the appropriate context with the presence of obstructive CAD. Conversely, initial results of the assessment of a longitudinal hyperemic flow gradient suggest this novel flow parameter to be specifically related to increases in CAD caused epicardial resistance. The concurrent assessment of myocardial perfusion and several hyperemic flow parameters with PET/CT may indeed open novel avenues of precision medicine to guide coronary revascularization procedures that may potentially lead to a further improvement in cardiovascular outcomes in CAD patients.

Reproducible Computer-Assisted Quantification of Myocardial Perfusion with Contrast-Enhanced Ultrasound

Myocardial perfusion can be quantified by myocardial contrast echocardiography (MCE) and is used for the diagnosis of coronary artery disease (CAD). However, existing MCE quantification software is highly operator dependent and has poor reproducibility and ease of usage. The aim of this study was to develop robust and easy-to-use software that can perform MCE quantification accurately, reproducibly and rapidly. The developed software has the following features: (i) semi-automatic segmentation of the myocardium; (ii) automatic rejection of MCE data with poor image quality; (iii) automatic computation of perfusion parameters such as myocardial blood flow (MBF). MCE sequences of 18 individuals (9 normal, 9 with CAD) undergoing vasodilator stress with dipyridamole were analysed quantitatively using the software. When evaluated against coronary angiography, the software achieved a sensitivity of 71% and a specificity of 91% for hyperemic MBF. With the automatic rejection algorithm, the sensitivity and specificity further improved to 77% and 94%, respectively. For MBF reproducibility, the percentage agreement is 85% (κ = 0.65) for inter-observer variability and 88% (κ = 0.72) for intra-observer variability. The intra-class correlation coefficients are 0.94 (inter-observer) and 0.96 (intra-observer). The time taken to analyse one MCE sequence using the software is about 3 min on a PC. The software has exhibited good diagnostic performance and reproducibility for CAD detection and is rapid and user-friendly.