Regional Myocardial Blood Flow Research Articles

Going beyond summed stress scores: Correlating global and territorial coronary flow reserve by single photon emission tomography with routine myocardial perfusion imaging

(a) BackgroundTechnological advancement in the recent years has enabled the application of single photon emission tomography (SPECT) to evaluate myocardial blood flow (MBF). This method offers increased sensitivity in the assessment of coronary health, quantifiable through non-invasive imaging beyond the more conventional methods such as with myocardial perfusion imaging (MPI). (b) AimsTo correlate MBF, derived by dynamic SPECT, both global and by coronary territories to the summed stress scores (SSS) on conventional MPI. (c) MethodsImages obtained from dipyridamole-gated SPECT MPI stress and rest studies performed on recruited subjects were examined. We calculated the global and regional coronary flow reserve (CFR) via a standard software package, taken as the ratio of stress MBF to rest MBF, using CFR<2.5 as the cut off. (d) ResultsAmongst the 90 recruited subjects (mean age 67 ± 8 years; of which 76% were males), 49% had MPI within normal limits (summed stress score (SSS) 0–3; Left ventricular ejection fraction (LVEF) > 50%). We observed a progressive reduction in global and regional CFR across the normal SSS category to that of severely abnormal (SSS >13). Reduced global CFR with correspondent lower CFR across the regional arteries were detected in scans within normal limits of MPI scans in subjects who were older (69 ± 7 vs. 62 ± 9 years, p = 0.034). Decreasing CFR was significantly associated with increasing age across the regional arteries. (e) ConclusionIn our study we depict the global and regional MBF values obtained via SPECT MPI in correlation to the respective SSS categories. Our data proposes that dynamic SPECT has a part in refining cardiac risk stratification, particularly in the older adult population, who are at greater risk.

The Influence of Kinetic Models and Attenuation Correction on Cadmium-Zinc-Telluride Single-Photon Emission Computed Tomography (CZT SPECT)-Derived Myocardial Blood Flow and Reserve: Correlation with Invasive Angiography Data.

(1) Background: The objective of this study was to determine the optimal post-processing model for dynamic cadmium-zinc-telluride single-photon emission computed tomography (CZT-SPECT). (2) Methods: A total of 235 patients who underwent diagnostic invasive coronary angiography within three months of the SPECT and those who had coronary computed tomography angiography (CCTA) before SPECT (within 3 months) were enrolled in this study. Each SPECT study was processed to obtain global and regional stress myocardial blood flow (sMBF), rest-MBF (rMBF), myocardial flow reserve (MFR) and flow difference (FD) estimates obtained with 1-tissue-compartment (1TCM) and net retention (NR) modes, both with and without attenuation correction. (3) Results: The use of AC led to significantly higher sMBF, rMBF and DF values obtained by 1TCM compared those values derived by 1TCM with NAC; the lowest values of stress MBF and rest MBF were obtained by 1TCM_NAC. The resting flow, MFR and DF were significantly (p < 0.005) higher in the AC model than in NAC. All quantitative variables were significantly (p < 0.05) higher in NR_NAC than in the 1TC_NAC model. Finally, sMBF, rMBF and FD showed significantly (p < 0.05) higher values by using 1TMC_AC compared to NR_AC. (4) Conclusions: We suggested that 1-compartment and net retention models correctly reflect coronary microcirculation and can be used for clinical practice for evaluating quantitative myocardial perfusion by dynamic SPECT. Attenuation correction is an important step in post-processing dynamic SPECT data, which increases the consistency and diagnostic accuracy of models.

Feasibility of myocardial blood flow quantification to detect flow-limited coronary artery disease with a one-day rest/stress continuous rapid imaging protocol on cardiac-dedicated cadmium zinc telluride single photon emission computed tomography

BackgroundIt is clinically needed to explore a more efficient imaging protocol for single photon emission computed tomography (SPECT) myocardial blood flow (MBF) quantitation derived from cadmium zinc telluride (CZT) SPECT camera for the routine clinical utilization. MethodsOne hundred and twenty patients with matched clinical characteristics and angiographic findings who completed one-day rest/stress SPECT imaging with either the intermittently sequential imaging (ISI) protocol (two dynamic and two electrocardiography (ECG)-gated scans) or the continuous rapid imaging (CRI) protocol (two dynamic/ECG-gated scans) were included. MBF quantitation adopted residual activity correction (RAC) to correct for rest residual activity (RRA) in the stress dynamic SPECT scan for the detection of flow-limited coronary artery disease. ResultsThe CRI protocol reduced about 6.2 times shorter than the ISI protocol (25.5 min vs 157.6 min), but slightly higher than the RRA (26.7% ± 3.6% vs 22.3% ± 4.9%). With RAC, both protocols demonstrated close stress MBF (2.18 ± 1.13 vs 2.05 ± 1.10, P > 0.05) and myocardial flow reserve (MFR) (2.42 ± 1.05 vs 2.48 ± 1.11, P > 0.05) to deliver comparable diagnostic performance (sensitivity = 82.1%–92.3%, specificity = 81.2%–91.2%). Myocardial perfusion and left ventricular function overall showed no significant difference (all P > 0.26). ConclusionOne-day rest/stress SPECT with the CRI protocol and rest RAC is feasible to warrant the diagnostic performance of MBF quantitation with a shortened examination time and enhanced patient comfort. Further evaluation on the impact of extracardiac activity to regional MBF and perfusion pattern is required. Additional evaluation is needed in a patient population that is typical of those referred for SPECT MPI, including those with known or suspected coronary microvascular disease.

Validation of resting full-cycle ratio and diastolic pressure ratio with [15O]H2O positron emission tomography myocardial perfusion

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. The aim of this study was to validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of resting and hyperemic myocardial perfusion. Within a 2 week period, coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. PET derived regional hyperemic myocardial blood flow (hMBF) and myocardial perfusion reserve (MPR) served as reference standards. In coronary arteries with stenoses (43%, 136 of 320), the overall diagnostic accuracies of RFR, dPR, and FFR did not differ when PET hyperemic MBF < 2.3 ml min−1 (69.9%, 70.6%, and 77.1%, respectively) and PET MPR < 2.5 (70.6%, 71.3%, and 66.9%, respectively) were considered as the reference for myocardial ischemia. Non-significant differences between the areas under the receiver operating characteristic (ROC) curve were found between the different indices. Furthermore, the integration of FFR with RFR (or dPR) does not enhance the diagnostic information already achieved by FFR in the characterization of ischemia via PET perfusion. In conclusion, the novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance comparable to FFR in assessing regional myocardial ischemia. These findings suggest that RFR and dPR may be considered as an FFR alternative for invasively guiding revascularization treatment in symptomatic patients with CAD.

PET-determined myocardial perfusion and flow in coronary artery disease characterization

Positron emission tomography (PET) myocardial perfusion imaging in conjunction with tracer-kinetic modeling enables the concurrent assessment of myocardial perfusion and regional myocardial blood flow (MBF) of the left ventricle in absolute terms in milliliters per gram per minute (mL/g/min). The non-invasive quantification of MBF during pharmacologically induced hyperemia, at rest, and corresponding myocardial flow reserve (MFR) opens a new avenue for the identification and characterization of classical or endogen type of coronary microvascular dysfunction (CMD) as functional substrate for microvascular angina in patients with non-obstructive coronary artery disease (CAD) and/or no CAD at all. Further, PET-MBF quantification expands the scope of conventional myocardial perfusion imaging from the identification of advanced, and flow-limiting, epicardial CAD to early stages of atherosclerosis and/or CMD. Adding MBF assessment to myocardial perfusion may also reliably unravel diffuse ischemia owing to significant left main stenosis and/or multivessel CAD, confirmed by peak stress transient ischemic cavity dilation of the left ventricle during maximal vasomotor stress on gated PET images. Owing to high spatial and contrast resolution in conjunction with photon-attenuation free myocardial perfusion PET images, PET is preferentially used for CAD in advanced obesity and women with pronounced breast habitus. With increasing clinical use of cardiac PET perfusion and MBF assessment, individualized, and image-guided cardiovascular treatment decisions in CAD patients is likely to ensue, while its translation into improved cardiovascular outcome remains to be investigated.

Changes in myocardial perfusion after coronary sinus reducer implantation for refractory angina - assessment using fully automated quantitative stress perfusion cardiac MRI

Abstract Introduction Previous reports show angina improvement after Coronary Sinus Reducer (CSR) implantation [1,2]. However, the mechanistic basis remains unconfirmed. Preliminary studies using semi-quantitative metrics derived from stress perfusion cardiac MRI (CMR), have suggested improved myocardial perfusion particularly in ischaemic segments [3]. To date, assessment by fully automated quantitative myocardial perfusion CMR has not been reported. Purpose To assess the effect of CSR implantation on quantitative regional myocardial blood flow in patients with refractory angina and advanced coronary artery disease (CAD). Methods Prospective cohort study of patients undergoing CSR implantation. CMR was performed at baseline and median 7 months follow-up. Automated segmentation into a 16-segment American Heart Association model was performed to quantify segmental rest and stress myocardial blood flow (MBF, ml/min/g) and myocardial perfusion reserve (MPR). Rest MBF was corrected for heart rate by dividing by the scan heart rate and multiplying by the mean resting heart rate among all subjects. Wilcoxon matched-pairs sign rank tests were used to compare paired global and segmental perfusion values. A linear mixed-effects model with random slopes and intercepts was used to assess the relationship between baseline segmental MPR and associated change in MPR (ΔMPR) after CSR implantation. Results 12 patients (10M:2F; mean age 67) were included. Median Canadian Cardiovascular Society class was 3. Globally, there was no change in rest (P=0.90), stress MBF (P=0.34) or MPR (P=0.72) from baseline to follow-up. However, ΔMPR was related to the degree of baseline ischaemia (panel A). Segments with baseline MPR&amp;lt;2.45 increased in MPR whereas segments with baseline MPR ≥2.45 experienced a decrease (P=0.003, conditional R2: 0.81). In segments with MPR&amp;lt;2.45 (n=138), median ΔMPR was +0.18 (15.4%; P&amp;lt;0.0001); whereas with MPR≥2.45 (n=52) it was -0.41 (-12.7%; P=0.03; panel B). When assessed by myocardial layer, significant increases in MPR were observed in both subendocardial (+0.19 [15.6%]; P&amp;lt;0.0001) and subepicardial (+0.19 [12.3%]; P&amp;lt;0.0002) segments with baseline MPR&amp;lt; 2.45 (panel C). Conversely, in segments with baseline MPR≥2.45, there was a significant reduction in MPR in the subendocardium (-0.43 [-15.9%]; P=0.04) but not in the subepicardium (-0.36 [-9.90%]; P=0.08; panel D). Conclusion To our knowledge, this is the first study showing changes in quantitative myocardial perfusion after CSR implantation by fully automated inline quantitative perfusion CMR. Our analysis shows a relationship between baseline MPR and change in MPR after CSR implantation, supporting redistribution of perfusion into both subendocardial and subepicardial layers as potential mechanisms of action of CSR. Further studies are needed to confirm these preliminary results.

Assessment of resting myocardial blood flow in regions of known transmural scar to confirm accuracy and precision of 3D cardiac positron emission tomography

BackgroundComposite invasive and non-invasive data consistently demonstrate that resting myocardial blood flow (rMBF) in regions of known transmural myocardial scar (TMS) converge on a value of ~ 0.30 mL/min/g or lower. This value has been confirmed using the 3 most common myocardial perfusion agents (13N, 15O-H2O and 82Rb) incorporating various kinetic models on older 2D positron emission tomography (PET) systems. Thus, rMBF in regions of TMS can serve as a reference “truth” to evaluate low-end accuracy of various PET systems and software packages (SWPs). Using 82Rb on a contemporary 3D-PET-CT system, we sought to determine whether currently available SWP can accurately and precisely measure rMBF in regions of known TMS.ResultsMedian rMBF (in mL/min/g) and COV in regions of TMS were 0.71 [IQR 0.52–1.02] and 0.16 with 4DM; 0.41 [0.34–0.54] and 0.10 with 4DM-FVD; 0.66 [0.51–0.85] and 0.11 with Cedars; 0.51 [0.43–0.61] and 0.08 with Emory-Votaw; 0.37 [0.30–0.42], 0.07 with Emory-Ottawa, and 0.26 [0.23–0.32], COV 0.07 with HeartSee.ConclusionsSWPs varied widely in low end accuracy based on measurement of rMBF in regions of known TMS. 3D PET using 82Rb and HeartSee software accurately (0.26 mL/min/g, consistent with established values) and precisely (COV = 0.07) quantified rMBF in regions of TMS. The Emory-Ottawa software yielded the next-best accuracy (0.37 mL/min/g), though rMBF was higher than established gold-standard values in ~ 5% of the resting scans. 4DM, 4DM-FDV, Cedars and Emory-Votaw SWP consistently resulted values higher than the established gold standard (0.71, 0.41, 0.66, 0.51 mL/min/g, respectively), with higher interscan variability (0.16, 0.11, 0.11, and 0.09, respectively).Trial registration: clinicaltrial.gov, NCT05286593, Registered December 28, 2021, https://clinicaltrials.gov/ct2/show/NCT05286593.

Multiaxial pressure-strain analysis of regional myocardial work in the setting of graded coronary stenoses and dobutamine stress.

We present a detailed analysis of regional myocardial blood flow and work to better understand the effects of coronary stenoses and low-dose dobutamine stress. Our analysis is based on a unique open-chest model in anesthetized canines that features invasive hemodynamic monitoring, microsphere-based blood flow analysis, and an extensive three-dimensional (3-D) sonomicrometer array that provides multiaxial deformational assessments in the ischemic, border, and remote vascular territories. We use this model to construct regional pressure-strain loops for each territory and quantify the loop subcomponent areas that reflect myocardial work contributing to the ejection of blood and wasted work that does not. We demonstrate that reductions in coronary blood flow markedly alter the shapes and temporal relationships of pressure-strain loops, as well as the magnitudes of their total and subcomponent areas. Specifically, we show that moderate stenoses in the mid-left anterior descending coronary artery decrease regional midventricle myocardial work indices and substantially increase indices of wasted work. In the midventricle, these effects are most pronounced along the radial and longitudinal axes, with more modest effects along the circumferential axis. We further demonstrate that low-dose dobutamine can help to restore or even improve function, but often at the cost of increased wasted work. This detailed, multiaxial analysis provides unique insight into the physiology and mechanics of the heart in the presence of ischemia and low-dose dobutamine, with potential implications in many areas, including the detection and characterization of ischemic heart disease and the use of inotropic support for low cardiac output.NEW & NOTEWORTHY Our unique experimental model assesses cardiac pressure-strain relationships along multiple axes in multiple regions. We demonstrate that moderate coronary stenoses decrease regional myocardial work and increase wasted work and that low-dose dobutamine can help to restore myocardial function, but often with further increases in wasted work. Our findings highlight the significant directional variation of cardiac mechanics and demonstrate potential advantages of pressure-strain analyses over traditional, purely deformational measures, especially in characterizing physiological changes related to dobutamine.

Canagliflozin improves coronary microvascular vasodilation and increases absolute blood flow to the myocardium independent of angiogenesis

ObjectivesSodium-glucose cotransporter-2 inhibitor, canagliflozin, improves myocardial perfusion to ischemic territory without accompanying changes in vascular density. We aimed to (1) characterize effects on angiogenic pathways, (2) use multiomics to identify gene expression and metabolite profiles relevant to regulation of myocardial blood flow, and (3) investigate drug effect on coronary microvascular reactivity. MethodsA nondiabetic swine model of chronic myocardial ischemia and nondiabetic rat model were used to study functional and molecular effects of canagliflozin on myocardium and in vitro microvascular reactivity. ResultsCanagliflozin resulted in increased coronary microvascular vasodilation and decreased vasoconstriction (P < .05) without changes in microvascular density (P > .3). Expression of the angiogenic modulator, endostatin, increased (P = .008), along with its precursor, collagen 18 (P < .001), and factors that increase its production, including cathepsin L (P = .004). Endostatin and collagen 18 levels trended toward an inverse correlation with blood flow to ischemic territory at rest. Proangiogenic fibroblast growth factor receptor was increased (P = .03) and matrix metalloproteinase-9 was decreased (P < .001) with canagliflozin treatment. Proangiogenic vascular endothelial growth factor A (P = .13), Tie-2 (P = .10), and Ras (P = .18) were not significantly altered. Gene expression related to the cardiac renin-angiotensin system was significantly decreased. ConclusionsIn chronic myocardial ischemia, canagliflozin increased absolute blood flow to the myocardium without robustly increasing vascular density or proangiogenic signaling. Canagliflozin resulted in altered coronary microvascular reactivity to favor vasodilation, likely through direct effect on vascular smooth muscle. Downregulation of cardiac renin-angiotensin system demonstrated local regulation of perfusion. Video Abstract [Display omitted]

Impact of Motion Correction tools on reliability and agreement of three software packages for dynamic- perfusion PET/CT processing

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): University of Groningen/University Medical Centre Groningen. Background PET/CT plays an important role in the evaluation of patients with CAD. It allows for non-invasive assessment of coronary function, by means of software based estimations of regional and global myocardial blood flow (MBF) and coronary flow reserve (CFR). However, measurements can differ between software vendors. Also, motion artifacts can impact their reliability. Literature stands that motion can lead to differences up to 500%. In-software motion correction (ISMC) tools are available in some processing software packages, however they rely on different algorithms and their specific role is yet unknown. Recently, an innovative data driven motion correction (DDMC) algorithm was developed, that specifically tracks and corrects for motion prior the reconstruction process. This opens up the possibility of an standardized MC technique. Purpose This study aims to determine the impact of ISMC and DDMC on the reproducibility and agreement of MBF/CFR values between three software packages for dynamic PET processing. It was hypothesized that the use of MC techniques improves agreement/reproducibility in these parameters between vendors. Methods Twenty-three patients categorized as normal after a 13N-ammonia PET/CT examination acquired between July-December 2020 were retrospectively included. Inclusion criteria: no history of CAD, no perfusion defects, normal LV-function and no MACEs and/or relapse at follow up. These criteria were used to prevent possible interference to MBF/CFR values by concomitant CAD. Reconstructions were made without motion correction (NMC), with ISMC and with DDMC. These reconstructions were analyzed in three different software: Corridor 4DM [4DM], Cedars-Sinai QPET [QPET], and SyngoMBF [Syngo]. Clinical data, as well as regional and global values of MBF in rest and stress and CFR were acquired for the final analysis. Paired T-tests, Bland Altman plots and intraclass correlation coefficients were used for statistical analysis. Results Study population consisted of 15(65%) woman, all patients &amp;gt;60 yo, and 21(91%) of adenosine stress (9% regadenoson). The impact of the MC techniques varied between technique, software and region. Differences ranged from −0.12 (QPET DDMC in RCA stress-MBF) to +0.81 (Syngo ISMC in RCA CFR) ml/g/min. QPET proved to be more sensitive to MC, as significant changes in all regional and global stress-MBF and CFR were detected after applying any MC technique (p&amp;lt;0.001). Bland-Altman plots showed heterogeneous results after the use of MC, with some territories improving the Bias and LoA but the opposite in others. Finally, absolute agrement by ICC was predominantly better when using DDMC compared to NMC and ISMC. Only DDMC achieved an ICC &amp;gt;0.9 (excellent) in the RCA CFR. Conclusions The use of DDMC improves the reliability of regional and global stress MBF and CFR in all packages when compared to the use of ISMC or NMC, however, the impact of DDMC is heterogeneous between the packages.

Diagnostic accuracy of dynamic stress myocardial ct perfusion as compared with invasive coronary physiology assessment in patients with suspected ISR or CAD progression: results of ADVANTAGE II study

Abstract Funding Acknowledgements Type of funding sources: None. Objectives To compare the diagnostic performance of regadenosone-stress dynamic myocardial perfusion assessed by CT (CTP) as compared with that of coronary CT angiography (CCTA) alone by using invasive fractional flow reserve (FFR) and index of microvascular resistance (IMR) as standard of reference. Background Diagnostic performance of CCTA for in-stent restenosis (ISR) detection is still challenging. Recently, CTP demonstrated additional specificity and diagnostic accuracy over CCTA alone in patients with previous stent implantation and suspected IRS or progression of coronary artery disease (CAD). However, no data are available in this clinical setting on the performance of CTP by using a new technique allowing for a non-invasive adjudication of regional myocardial blood flow (Dynamic CTP) and to assess both macrovascular and microvascular disease status. Methods We enrolled consecutive stable patients with previous coronary stenting referred for invasive quantitative coronary angiography (QCA) for clinical indication. All patients underwent dynamic stress myocardial CTP and rest CTP+CCTA by using a last generation scanner characterized by a 16-cm Z-axis coverage and fast (0.28 sec) gantry rotation time. Invasive FFR and IMR were performed during QCA according to the standard practice. The diagnostic rate and diagnostic accuracy of CCTA and CTP were evaluated in a territory-based analyses vs. FFR, IMR (primary endpoint of the study) and QCA (secundary endpoint). Results In 156 enrolled patients (126 men, mean age 63.1±8.2 years), the diagnostic rate (number of territories interpretable/number of territories evaluated) of CTP was significantly higher than that of CCTA (789/799=98.7% vs. 764/799=95.6%; p = 0.0002). The mean absolute MBF values for ischemic territories (pathological FFR and/or IMR) was significantly lower as compared with those for normal territories (96 ± 32 ml/100 g/min vs. 130 ± 46 ml/100 g/min; p&amp;lt; 0.0001). When FFR was used as gold standard, sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of CTP were higher than those of CCTA (89%, 82.8%, 69.2%, 94.6% and 84.7% vs. 60%, 61.9%, 31.9%, 83.8% and 61.5%, p&amp;lt;0.001, respectively). When IMR was used as gold standard, sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of CTP were higher than those of CCTA (76.5%, 85.9%, 72.2%, 88.4% and 82.9% vs. 48.2%, 63.5%, 33.3%, 76.4% and 59.3%, p&amp;lt;0.01, respectively). When the presence of at least one abnormal physiological parameter among FFR and IMR was used as gold standard, the diagnostic accuracy of CTP was higher than that of CCTA (90.8% vs. 68.1%, p&amp;lt;0.001). The mean ED of the total CCTA/rest CTP/stress CTP was 5.63±4.2 mSv. Conclusion In patients with coronary stents, dynamic CTP significantly improves diagnostic rate and accuracy of CCTA alone in comparison with both FFR and IMR.

No robust reduction of infarct size and no-reflow by metoprolol pretreatment in adult Göttingen minipigs

Whereas prior experiments in juvenile pigs had reported infarct size reduction by intravenous metoprolol early during myocardial ischaemia, two major clinical trials in patients with reperfused acute myocardial infarction were equivocal. We, therefore, went back and tested the translational robustness of infarct size reduction by metoprolol in minipigs. Using a power analysis-based prospective design, we pretreated 20 anaesthetised adult Göttingen minipigs with 1 mg kg−1 metoprolol or placebo and subjected them to 60-min coronary occlusion and 180-min reperfusion. Primary endpoint was infarct size (triphenyl tetrazolium chloride staining) as a fraction of area at risk; no-reflow area (thioflavin-S staining) was a secondary endpoint. There was no significant reduction in infarct size (46 ± 8% of area at risk with metoprolol vs. 42 ± 8% with placebo) or area of no-reflow (19 ± 21% of infarct size with metoprolol vs. 15 ± 23% with placebo). However, the inverse relationship between infarct size and ischaemic regional myocardial blood flow was modestly, but significantly shifted downwards with metoprolol, whereas ischaemic blood flow tended to be reduced by metoprolol. With an additional dose of 1 mg kg−1 metoprolol after 30-min ischaemia in 4 additional pigs, infarct size was also not reduced (54 ± 9% vs. 46 ± 8% in 3 contemporary placebo, n.s.), and area of no-reflow tended to be increased (59 ± 20% vs. 29 ± 12%, n.s.).Infarct size reduction by metoprolol in pigs is not robust, and this result reflects the equivocal clinical trials. The lack of infarct size reduction may be the result of opposite effects of reduced infarct size at any given blood flow and reduced blood flow, possibly through unopposed alpha-adrenergic coronary vasoconstriction.

Influence of image reconstruction on quantitative cardiac 15O-water positron emission tomography

BackgroundThe impact on quantitative 15O-water PET/CT of a wide range of different reconstruction settings, including regularized reconstruction by block-sequential regularized expectation maximization (BSREM), was investigated. MethodsTwenty clinical stress scans from patients referred for assessment of myocardial ischemia were included. Patients underwent a 4-min dynamic stress PET scan with 15O-water on a digital PET/CT scanner. Twenty-two reconstructions were generated from each scan and a clinical reconstruction was used as reference. Varied parameters were number of iterations, filter, exclusion of time-of-flight and point-spread function, and regularization parameter with BSREM. Analyses were performed in aQuant utilizing two different methods and resulting regional myocardial blood flow (MBF), perfusable tissue fraction (PTF), and transmural MBF (MBFt) values were evaluated. ResultsAcross the two analyses, correlations toward the reference reconstruction were strong for all parameters (ρ ≥ 0.83). Using automated analysis and the diagnostic threshold of hyperemic MBF at 2.3 mL⋅g−1⋅min−1, diagnosis was unchanged irrespective of reconstruction method in all patients except for one, where only four of the most extreme reconstruction methods resulted in a change of diagnosis. ConclusionThe low sensitivity of MBF values to reconstruction method and, as previously shown, scanner type and PET/CT misalignment, confirms that diagnostic hyperemic MBF cutoff values can be consistently used for 15O-water.

RB-82 PET DERIVED REGIONAL MYOCARDIAL BLOOD FLOW IS ASSOCIATED WITH ALL-CAUSE MORTALITY IN PATIENTS PRESENTING WITH ACUTE CHEST PAIN

RB-82 PET DERIVED REGIONAL MYOCARDIAL BLOOD FLOW IS ASSOCIATED WITH ALL-CAUSE MORTALITY IN PATIENTS PRESENTING WITH ACUTE CHEST PAIN

Abstract 10128: Recombinant Human Placental Growth Factor-2 Treatment in Porcine Ischemic Cardiomyopathy

Background: Placental growth factor (PlGF)-2 induces neovascularization and improves myocardial function in atherosclerotic rodent myocardial ischemia models without stimulating plaque angiogenesis. This promising therapeutic profile of PlGF-2 warrants a double blind, randomized, and placebo-controlled feasibility and efficacy study in a large animal model, representative of human disease. Methods: We induced myocardial infarction (MI) in domestic pigs using a 75 min balloon occlusion of the mid-LAD followed by reperfusion. After 4 w, we randomized pigs with marked LV dysfunction (LVEF&lt;40%) to continuous IV infusion of 5, 15, 45 μg/kg/day rhPlGF-2 or PBS (CON) for 2 w using osmotic pumps. We evaluated treatment effect 8 w after MI using comprehensive MRI analysis of LV function and structure and performed postmortem histological analyses of LV vascularization and fibrotic remodeling. Results: In the pilot study (3 pigs/dose), PIGF plasma concentrations showed stable and sustained dose-dependent increases for 28 days without organ-specific side effects or systemic toxicity. Myocardial Ischemia/reperfusion induced LV dysfunction at 4 w (infarct size, 16±4 % of LV mass, n=42; LVEF, 34±4 %, range 19%-40%). In the dose escalation study using 5 (n=10), 15 or 45 μg/kg/day PlGF (n=11 per group), global LV function, and regional myocardial blood flow at rest or during stress, and infarct size did not differ between CON (n=10) and PlGF (Figure 1). Capillary densities and extent of LV interstitial fibrosis in infarct core and border zone were comparable between CON and PlGF. Conclusions: In this blinded randomized controlled trial, rhPIGF-2 did not improve global cardiac function in a porcine model of chronic ischemic cardiomyopathy, and failed to recapitulate therapeutic neovascularization reported in rodents. Our data emphasize the critical need for robust double blind, placebo controlled trials in representative large animal models before clinical translation.

Diagnostic value of computed tomography myocardial perfusion to detect coexisting microvascular dysfunction in patients with obstructive epicardial coronary disease

Abstract Background The usefulness of computed tomography myocardial perfusion (CTP) to assess hemodynamically significant epicardial coronary artery lesions has been previously reported. However, the diagnostic value of quantitative evaluation of absolute coronary flow by CTP to detect microvascular dysfunction remains unknown. Purpose The aim of study is to assess the diagnostic value of CTP to evaluate coronary microvascular dysfunction (CMD) in patients with significant epicardial coronary stenosis, and to analyze the predicting factors for lesions with CMD. Methods Sixty-eight chronic coronary syndrome patients with de novo single functionally significant stenosis (Fractional flow reserve [FFR] &amp;lt;0.80) were investigated. CMD was defined by the index of microcirculatory resistance (IMR) ≥25. Clinical characteristics and CTP findings were compared between the two groups with and without CMD (CMD, n=29, non-CMD, n=39, respectively). The computed tomography angiography (CCTA) assessment included CTP findings and quantitative and qualitative assessment of plaques. Results In wire-based analysis, FFR, coronary flow reserve (CFRwire) and IMR were 0.68 (0.59–0.74), 1.71 (1.24–2.88), and 22.6 (15.1–34.5), respectively. In CTP analysis, culprit territory regional absolute myocardial blood flow (MBF) at rest (rest-MBF) and hyperemia (hyperemic-MBF) were evaluated semi-automatically. CTP-derived CFR (CFRCTP) was calculated as hyperemic-MBF divided by rest-MBF. Rest and hyperemic-MBF and CFRCTP were 0.83 (0.64–1.03) ml/min/g, 2.14 (1.30–2.92) ml/min/g, and 2.19 (1.44–3.37). In the lesions with CMD, hyperemic-MBF was significantly lower than those without CMD (1.68 [0.84–2.44] vs 2.31 [1.67–3.34] ml/min/g, p=0.015) and the prevalence of CFRCTP&amp;lt;2.0 was higher in the lesions with CMD than those without CMD (62.1% vs 28.2%, p=0.007). CCTA analysis showed that fibrofatty and necrotic core component (FFNC) volume was greater in the lesions with CMD than in the lesions without CMD (31.8 [19.0–48.9] vs 25.1 [17.2–32.1] mm3, p=0.045). The multivariable logistic regression analysis, hyperemic-MBF and FFNC volume were independent predictors for lesions with CMD (Odds ratio [OR] 0.583 [0.355–0.958], p=0.033 and OR 1.040 [1.010–1.070], p=0.018). Conclusion Quantitative assessment of absolute coronary flow by CTP and comprehensive plaque analysis by CCTA may help detect coexisting subtended microvascular dysfunction in patients with functionally significant epicardial coronary lesions. Further studies are needed to elucidate the clinical significance of coexisting CMD in CCS patients. Funding Acknowledgement Type of funding sources: None.

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.

Myocardial Blood Flow and Flow Reserve in Patients With Acute Myocardial Infarction and Obstructive and Non-Obstructive Coronary Arteries: CZT SPECT Study

BackgroundTo assess single-photon emission computed tomography cadmium-zinc-telluride (SPECT CZT)-derived myocardial blood flow (MBF) flow reserve (MFR) and flow difference (FD) in patients with acute myocardial infarction (AMI) and to compare this data with serum cardiac troponin and cardiac magnetic resonance (CMR) findings.MethodsA total of 31 patients with AMI underwent invasive coronary angiography (ICA), serial high-sensitivity serum cardiac troponin I (cTnI) measurement, and CZT SPECT with visual and quantitative (MBF, MFR, and FD) perfusion parameters, and contrast-enhanced CMR. All patients with AMI were divided into two groups: (1) with non-obstructive coronary arteries (MINOCA), n = 10; (2) with obstructive coronary artery disease (MICAD), n = 21.ResultsThe values of SSS and SRS were significantly (p &amp;lt; 0.01) higher whereas global stress MBF, MFR significantly lower in patients with MICAD as compared to MINOCA – 5.0 (3.0; 5.0) vs. 9.0 (5.0; 13.0); 2.0 (1.0; 3.0) vs. 6.0 (3.0; 11.0); 2.02 (1.71; 2.37) vs. 0.86 (0.72; 1.02) ml/min/g; and 2.61 (2.23; 3.14) vs. 1.67 (1.1; 1.9), respectively. Stress MBF correlated with cTnI at 24 h and day 4: ρ = −0.39; p = 0.03 and ρ = −0.47; p = 0.007, respectively. FD correlated with cTnI at 24 h and day 4: ρ = −0.39; p = 0.03 and ρ = −0.46; p = 0.009. CMR analysis showed that infarct size, MVO and myocardial edema in patients with MICAD were significantly (&amp;lt; 0.05) higher as compared to MINOCA: 19.4 (10.4; 29.7) vs. 1.8 (0.0; 6.9); 0.1 (0.0; 0.7) vs. 0.0 (0.0; 0.0) and 19.5 (12.0;30.0) vs. 3.0 (0.0; 12.0), respectively. According to vessel-based analysis of CMR data, acute myocardial injury (defined as late gadolinium enhancement and myocardial edema) was observed more frequently in patients with MICAD compared to MINOCA: 34(37%) vs. 5(5%) p = 0.005, respectively. The values of regional stress MBF, MFR and FD were significantly decreased in LV territories characterized by myocardial injury compared to those without: 0.98 (0.73; 1.79) vs. 1.33 (0.94; 2.08) p &amp;lt; 0.01, 1.64 (1.0; 2.36) vs. 2.0 (1.53; 2.89) p &amp;lt; 0.01 and 0.33 (0.05; 0.57) vs. 0.56 (0.36; 1.32) p&amp;gt; 0.01, respectively.ConclusionIn patients with AMI, SPECT CZT-derived flow measures were associated with the high-sensitivity troponin I as well as the extent of edema, microvascular obstruction, and infarct size detected by CMR. On the regional level, quantitative SPECT CZT measures were significantly lower in vessel territories characterized by myocardial injury.

Highlights From the Circulation Family of Journals

Highlights From the <i>Circulation</i> Family of Journals

Quantitative myocardial perfusion 82Rb-PET assessed by hybrid PET/coronary-CT: Normal values and diagnostic performance

PurposeWe aimed to assess normal values for quantified myocardial blood flow (MBF) on a hybrid PET/coronary-CT scanner and to test their diagnostic performance in patients with suspected CAD. Materials and MethodsPatients underwent 82Rb-PET/CT and integrated CT-based coronary angiography (CCTA) and were classified as normal (no stenosis), with non-obstructive stenosis (< 50%) and with CAD (≥ 50%). Global and regional stress MBF (sMBF), rest MBF and myocardial flow reserve (MFR) were calculated. Ischemia was defined as SDS ≥ 2, severe ischemia as SDS ≥ 7. Results357 consecutive patients were included. Global sMBF and MFR were higher in normal patients than in patients with CAD (3.61 ± 0.71 vs 3.04 ± 0.77, P < 0.0001; 3.08 ± 0.84 vs 2.68 ± 0.79, P = 0.0001), but not different compared to patients with non-obstructive stenosis (3.61 ± 0.71 vs 3.43 ± 0.69, P = 0.052; 3.08 ± 0.84 vs 2.99 ± 0.82, P = 0.45). sMBF yielded superior accuracy over MFR in identifying both ischemia (AUC 0.74 vs 0.62, P = 0.003) and severe ischemia (AUC 0.88 vs 0.78, P = 0.012). Optimal threshold for global sMBF to rule out myocardial ischemia was 3.5 mL g−1 min−1. ConclusionsNormal quantitative values are provided. Global sMBF provided higher diagnostic accuracy than MFR. Using sMBF-threshold of 3.5 mL·g−1·min−1 on 82Rb-PET/CT yielded similar NPV (96%) as CCTA to rule out CAD. Hence, resting scan could be omitted in patients with sMBF values above reference.