Absolute Myocardial Blood Flow Research Articles

Emerging Techniques for Cardiovascular PET.

The application of positron emission tomography (PET) to cardiac disease has yielded tremendous developments in the evaluation of coronary artery, myocardial, and valvular heart disease over the past several decades. These advances have included development of new radiotracers, incremental technological improvements, and coupling of PET with other non-invasive cardiac imaging modalities. The current era has seen rapid, successive and wide-ranging advances in PET myocardial perfusion and metabolic imaging. This review will address emerging techniques in cardiovascular PET imaging, including the measurement of absolute myocardial blood flow (MBF), use of novel tracers, and other advances in heart failure, infection imaging, and valvular disease.

Acute Microvascular Impairment Post-Reperfused STEMI Is Reversible and Has Additional Clinical Predictive Value: A CMR OxAMI Study

ObjectivesThis study sought to investigate the clinical utility and the predictive relevance of absolute rest myocardial blood flow (MBF) by cardiac magnetic resonance (CMR) in acute myocardial infarction. BackgroundMicrovascular obstruction (MVO) remains one of the worst prognostic factors in patients with reperfused ST-segment elevation myocardial infarction (STEMI). Clinical trials have focused on cardioprotective strategies to maintain microvascular functionality, but there is a need for a noninvasive test to determine their efficacy. MethodsA total of 64 STEMI patients post–primary percutaneous coronary intervention underwent 3-T CMR scans acutely and at 6 months (6M). The protocol included cine function, T2-weighted edema imaging, pre-contrast T1 mapping, rest first-pass perfusion, and late gadolinium enhancement imaging. Segmental MBF, corrected for rate pressure product (MBFcor), was quantified in remote, edematous, and infarcted myocardium. ResultsAcute MBFcor was significantly reduced in infarcted myocardium compared with remote MBF (MBFinfarct 0.76 ± 0.20 ml/min/g vs. MBFremote 1.02 ± 0.21 ml/min/g, p < 0.001), but it significantly increased at 6M (MBFinfarct 0.76 ± 0.20 ml/min/g acute vs. 0.85 ± 0.22 ml/min/g at 6M, p < 0.001). On a segmental basis, acute MBFcor had incremental prognostic value for infarct size at 6M (odds of no LGE at 6M increased by 1.4:1 [p < 0.001] for each 0.1 ml/min/g increase of acute MBFcor) and functional recovery (odds of wall thickening >45% at 6M increased by 1.38:1 [p < 0.001] for each 0.1 ml/min/g increase of acute MBFcor). In subjects with coronary flow reserve >2 or index of myocardial resistance <40, acute MBF was associated with long-term functional recovery and was an independent predictor of infarct size reduction. ConclusionsAcute MBF by CMR could represent a novel quantitative imaging biomarker of microvascular reversibility, and it could be used to identify patients who may benefit from more intensive or novel therapies.

The Optimal Start Timing of Helical Scan for Coronary CT Angiography and CT Myocardial Perfusion Scan Using 64-MDCT

Ichihara et al. (Fujita Med J 2015; 1(1): 9-14) developed a method to simultaneously obtain both coronary computed tomography (CT) angiography and CT myocardial perfusion (CTP) using 64-multi detector CT (MDCT). An input-function (time enhancement curve, TEC) of the ascending aorta (Ao) and myocardial CT density are necessary to calculate absolute myocardial blood flow (ml/g/min) using a two-compartment model. Helical scan starting timing is important to capture the peak (P) of Ao time enhancement curve (TEC). The purpose is to search the optimal timing of starting helical scan to capture the P. We performed 14 CTPs using Definition AS+ (SIEMENS). A dynamic scan at the Ao level was started at 7 s after contrast injection and helical scan was started at various trigger on bolus tracking. Definition AS+ needs 2 s (other scanner may need 4 s) for changing from a dynamic to helical scan mode. We created TECs of pulmonary artery (PA) and Ao using the fifth function fitting. We measured the time from trigger point to the P (t200, t250, t300 and tCP). Mean t200, t250, t300 and tCP were 9.1±1.9, 7.9±2.0, 6.6±1.9 and 3.9±1.2 s, respectively. In additional other 16 CTP studies using the cross point method, we can capture the P in all (100%) examinations. Scan starting at the cross point is best for Definition AS+, and the Ao=300 HU may be best for other scanner that needs 4 s for changing scan mode to obtain a fine input function for calculating absolute myocardial blood flow.

Myocardial Perfusion Imaging for the Evaluation of Ischemic Heart Disease in Women

To review the value of myocardial blood flow and coronary flow reserve (CFR) measurements, as assessed by positron emission tomography (PET), in women with suspected ischemic heart disease. CFR is a noninvasive measure of coronary vasomotor function that integrates the hemodynamic effects of epicardial coronary stenosis, diffuse atherosclerosis, and microvascular dysfunction on myocardial tissue perfusion and has emerged as an imaging marker of cardiovascular risk, independently of the degree of obstructive coronary artery disease (CAD). Normal coronary arteries or nonobstructive CAD is a common finding in women with ischemia. Thus, assessment of risk based on a coronary stenosis approach may fail in women. PET is able to quantify absolute myocardial blood flow and CFR which may help to elucidate other mechanisms involved such as microvascular dysfunction and diffuse epicardial CAD, responsible for the disease in women.

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.

Coronary circulation: Pressure/flow parameters for assessment of ischemic heart disease

Both invasive and non-invasive parameters have been reported for assessment of the physiological status of the coronary circulation. Fractional flow reserve and coronary (or myocardial) flow reserve may be obtained by invasive or non-invasive means. These metrics of coronary stenosis severity have achieved wide clinical acceptance for guiding revascularization decisions and risk stratification. Other indices are obtained invasively (e.g., instantaneous wave-free ratio, iFR; hyperemic stenosis resistance) or non-invasively (e.g., PET absolute myocardial blood flow (mL/min/g)) and have been used for the same purposes. Both iFR, and whole-cycle distal coronary to aortic mean pressure (Pd/Pa) are measured under basal condition and used for assessment of hemodynamic stenosis severity as is index of basal stenosis resistance (BSR). These metrics typically are dichotomized at an empirically derived cut point into “normal” and “abnormal” categories for purposes of clinical decision making and data analysis. Once dichotomized the indices do not always point in the same direction and so confusion may arise. This review, therefore, will present basic principles relevant to understanding commonly employed metrics of the physiological status of the coronary circulation, potential strengths and weaknesses, and hopefully an improved appreciation of the clinical information provided by each.

Matrix Metalloproteinase-2 Impairs Homing of Intracoronary Delivered Mesenchymal Stem Cells in a Porcine Reperfused Myocardial Infarction: Comparison With Intramyocardial Cell Delivery.

Intracoronary (IC) injection of mesenchymal stem cells (MSCs) results in a prompt decrease of absolute myocardial blood flow (AMF) with late and incomplete recovery of myocardial tissue perfusion. Here, we investigated the effect of decreased AMF on oxidative stress marker matrix metalloproteinase-2 (MMP-2) and its influence on the fate and homing and paracrine character of MSCs after IC or intramyocardial cell delivery in a closed-chest reperfused myocardial infarction (MI) model in pigs. Porcine MSCs were transiently transfected with Ad-Luc and Ad-green fluorescent protein (GFP). One week after MI, the GFP-Luc-MSCs were injected either IC (group IC, 11.00 ± 1.07 × 106) or intramyocardially (group IM, 9.88 ± 1.44 × 106). AMF was measured before, immediately after, and 24 h post GFP-Luc-MSC delivery. In vitro bioluminescence signal was used to identify tissue samples containing GFP-Luc-MSCs. Myocardial tissue MMP-2 and CXCR4 receptor expression (index of homing signal) were measured in bioluminescence positive and negative infarcted and border, and non-ischemic myocardial areas 1-day post cell transfer. At 7-day follow-up, myocardial homing (cadherin, CXCR4, and stromal derived factor-1alpha) and angiogenic [fibroblast growth factor 2 (FGF2) and VEGF] were quantified by ELISA of homogenized myocardial tissues from the bioluminescence positive and negative infarcted and border, and non-ischemic myocardium. Biodistribution of the implanted cells was quantified by using Luciferase assay and confirmed by fluorescence immunochemistry. Global left ventricular ejection fraction (LVEF) was measured at baseline and 1-month post cell therapy using magnet resonance image. AMF decreased immediately after IC cell delivery, while no change in tissue perfusion was found in the IM group (42.6 ± 11.7 vs. 56.9 ± 16.7 ml/min, p = 0.018). IC delivery led to a significant increase in myocardial MMP-2 64 kD expression (448 ± 88 vs. 315 ± 54 intensity × mm2, p = 0.021), and decreased expression of CXCR4 (592 ± 50 vs. 714 ± 54 pg/tissue/ml, p = 0.006), with significant exponential decay between MMP-2 and CXCR4 (r = 0.679, p < 0.001). FGF2 and VEGF of the bioluminescence infarcted and border zone of homogenized tissues were significantly elevated in the IM goups as compared to IC group. LVEF increase was significantly higher in IM group (0.8 ± 8.4 vs 5.3 ± 5.2%, p = 0.046) at the 1-month follow up. Intracoronary stem cell delivery decreased AMF, with consequent increase in myocardial expression of MMP-2 and reduced CXCR4 expression with lower level of myocardial homing and angiogenic factor release as compared to IM cell delivery.

PET Assessment of Epicardial Intimal Disease and Microvascular Dysfunction in Cardiac Allograft Vasculopathy

BackgroundCardiac allograft vasculopathy (CAV) is a leading cause of graft failure and death after heart transplantation. Absolute myocardial blood flow (MBF) quantification using rubidium 82 (Rb-82) positron emission tomography (PET) could enable evaluation of diagnostically challenging diffuse epicardial and microvascular disease in CAV. ObjectivesThe authors aimed to evaluate Rb-82 PET detection of CAV. MethodsConsecutive transplant recipients undergoing coronary angiography were prospectively evaluated with PET, multivessel intravascular ultrasound (IVUS), and intracoronary hemodynamics. CAV was defined as International Society of Heart and Lung Transplantation CAV1–3 on angiography and maximal intimal thickness ≥0.5 mm on IVUS. ResultsForty patients (mean age 56 years, 4.8 years post-transplant) completed evaluation. CAV was detected in 32 patients (80%) by IVUS and 14 (35%) by angiography. PET correlated significantly with invasive coronary flow indices: r = 0.29, rate-pressure product–adjusted myocardial flow reserve (cMFR) versus coronary flow reserve; r = 0.28, relative flow reserve versus fractional flow reserve; and r = 0.37, coronary vascular resistance (CVR) versus index of microcirculatory resistance. Patients with CAV or microvascular dysfunction had reduced cMFR and stress MBF and increased CVR. Receiver operator characteristic curves demonstrated good accuracy of PET for CAV on IVUS (area under the curve 0.77 to 0.81) and optimal diagnostic cutoffs of cMFR <2.9, stress MBF <2.3, and CVR >55. Combined PET assessment for CAV yielded excellent >93% sensitivity (>65% specificity) for 1 abnormal parameter and >96% specificity (>55% sensitivity) for 2 abnormal parameters. ConclusionsRb-82 PET flow quantification has high diagnostic accuracy for CAV, with potential for noninvasive evaluation after heart transplantation.

Technical aspects of acquiring and measuring myocardial blood flow: Method, technique, and QA

Measuring absolute myocardial blood flow (MBF) is becoming a common aid for diagnosing patients suspected to have coronary artery disease. An MBF study, however, requires a scanner with high count rate capability, is more susceptible to artifacts, and is much more technically involved than static imaging, which leads to a greater risk of artifactual results contaminating the final result. This technical note gives the reader an introductory understanding of the method for calculating MBF. It then describes the scanning protocol, potential pitfalls and how to recognize them, and quality control steps that should be taken to avoid basing a clinical decision on possibly inaccurate flow information.

Motion Correction and Its Impact on Absolute Myocardial Blood Flow Measures with PET.

Motion artifacts, due to cardiac and respiratory cycles, myocardial cardiac creep, or gross patient movements, have been extensively investigated in the context of relative myocardial perfusion imaging with SPECT and PET. These movements have been identified as a major source of errors in image quantification and diagnosis. Recently, as dynamic PET quantification for myocardial blood flow assessment has entered clinical practice, similar questions have arisen on the impact of motion on final blood flow values. While preliminary investigations have underlined the potential impact of these motions on MBF quantification, their correction on dynamic acquisition remains challenging and limited to research studies. Gross patient's body movements occur in a consistent number of cases, particularly during stress acquisition, typically involving a limited number of image frames. If undetected, these movements can lead to great differences in flow values and consequently misdiagnosis. Quality control routines can be applied to automatically inspect the shape of time activity curves and to help identify motion artifacts. Cyclic cardiac and respiratory motion may have a considerable impact on final flow values. Correction of gross body motion represents a priority in the context of optimizing absolute flow clinical routine utilization and protocol standardization.

RELATIONSHIP BETWEEN GLOBAL MYOCARDIAL BLOOD FLOW EVALUATED BY PHASE CONTRAST CINE-MAGNETIC RESONANCE IMAGING AND REGIONAL PRESSURE WIRE-DERIVED PHYSIOLOGICAL INDICES

Recent studies proposed the integral of absolute regional peak stress myocardial flow and coronary flow reserve (CFR) for the assessment of ischemia and coronary physiology. However, few studies have documented the relationship between global absolute myocardial blood flow (MBF) and the regional

Diagnostic Performance of Fully Automated Pixel-Wise Quantitative Myocardial Perfusion Imaging by Cardiovascular Magnetic Resonance

ObjectivesThe authors developed a fully automated framework to quantify myocardial blood flow (MBF) from contrast-enhanced cardiac magnetic resonance (CMR) perfusion imaging and evaluated its diagnostic performance in patients. BackgroundFully quantitative CMR perfusion pixel maps were previously validated with microsphere MBF measurements and showed potential in clinical applications, but the methods required laborious manual processes and were excessively time-consuming. MethodsCMR perfusion imaging was performed on 80 patients with known or suspected coronary artery disease (CAD) and 17 healthy volunteers. Significant CAD was defined by quantitative coronary angiography (QCA) as ≥70% stenosis. Nonsignificant CAD was defined by: 1) QCA as <70% stenosis; or 2) coronary computed tomography angiography as <30% stenosis and a calcium score of 0 in all vessels. Automatically generated MBF maps were compared with manual quantification on healthy volunteers. Diagnostic performance of the automated MBF pixel maps was analyzed on patients using absolute MBF, myocardial perfusion reserve (MPR), and relative measurements of MBF and MPR. ResultsThe correlation between automated and manual quantification was excellent (r = 0.96). Stress MBF and MPR in the ischemic zone were lower than those in the remote myocardium in patients with significant CAD (both p < 0.001). Stress MBF and MPR in the remote zone of the patients were lower than those in the normal volunteers (both p < 0.001). All quantitative metrics had good area under the curve (0.864 to 0.926), sensitivity (82.9% to 91.4%), and specificity (75.6% to 91.1%) on per-patient analysis. On a per-vessel analysis of the quantitative metrics, area under the curve (0.837 to 0.864), sensitivity (75.0% to 82.7%), and specificity (71.8% to 80.9%) were good. ConclusionsFully quantitative CMR MBF pixel maps can be generated automatically, and the results agree well with manual quantification. These methods can discriminate regional perfusion variations and have high diagnostic performance for detecting significant CAD. (Technical Development of Cardiovascular Magnetic Resonance Imaging; NCT00027170)

Assessment of coronary vascular function with cardiac PET in relation to serum uric acid

BackgroundElevated serum uric acid (SUA) levels have been independently associated with cardiovascular disease. Stress myocardial perfusion positron emission tomography (PET) allows for measurement of absolute myocardial blood flow (MBF) and quantification of global left ventricular coronary flow reserve (CFR). A CFR <2.0 is considered impaired coronary vascular function, and it is associated with increased cardiovascular risk. We evaluated the relationship between SUA and PET-measured markers of coronary vascular function.MethodsWe studied adults undergoing a stress myocardial perfusion PET on clinical grounds (1/2006-3/2014) who also had ≥1 SUA measurement within 180 days from the PET date. Multivariable linear regression estimated the association between SUA and PET-derived MBF and CFR. We also stratified analyses by diabetes status.ResultsWe included 382 patients with mean (SD) age of 68.4 (12.4) years and mean (SD) SUA level of 7.2 (2.6) mg/dl. 36% were female and 29% had gout. Median [IQR] CFR was reduced at 1.6 [1.2, 2.0] and median [IQR] stress MBF was 1.5 [1.1, 2.1] ml/min/g. In the adjusted analysis, SUA was inversely associated with stress MBF (β = -0.14, p = 0.01) but not with CFR. Among patients without diabetes (n = 215), SUA had a negative association with CFR (β = -0.15, p = 0.02) and stress MBF (β = -0.19, p = 0.01) adjusting for age, sex, extent of myocardial scar and ischemia, serum creatinine and gout. In diabetic patients (n = 167), SUA was not associated with either CFR or MBF.ConclusionsIn this cross-sectional study, higher SUA is modestly associated with worse CFR and stress MBF among patients without diabetes.

Fully quantitative pixel-wise analysis of cardiovascular magnetic resonance perfusion improves discrimination of dark rim artifact from perfusion defects associated with epicardial coronary stenosis

BackgroundDark rim artifacts in first-pass cardiovascular magnetic resonance (CMR) perfusion images can mimic perfusion defects and affect diagnostic accuracy for coronary artery disease (CAD). We evaluated whether quantitative myocardial blood flow (MBF) can differentiate dark rim artifacts from true perfusion defects in CMR perfusion.MethodsRegadenoson perfusion CMR was performed at 1.5 T in 76 patients. Significant CAD was defined by quantitative invasive coronary angiography (QCA) ≥ 50% diameter stenosis. Non-significant CAD (NonCAD) was defined as stenosis by QCA < 50% diameter stenosis or computed tomographic coronary angiography (CTA) < 30% in all major epicardial arteries. Dark rim artifacts had study specific and guideline-based definitions for comparison purposes. MBF was quantified at the pixel-level and sector-level.ResultsIn a NonCAD subgroup with dark rim artifacts, stress MBF was lower in the subendocardial than midmyocardial and epicardial layers (2.17 ± 0.61 vs. 3.06 ± 0.75 vs. 3.24 ± 0.80 mL/min/g, both p < 0.001) and was also 30% lower than in remote regions (2.17 ± 0.61 vs. 2.83 ± 0.67 mL/min/g, p < 0.001). However, subendocardial stress MBF in dark rim artifacts was 37–56% higher than in true perfusion defects (2.17 ± 0.61 vs. 0.95 ± 0.43 mL/min/g, p < 0.001). Absolute stress MBF differentiated CAD from NonCAD with an accuracy ranging from 86 to 89% (all p < 0.001) using pixel-level analyses. Similar results were seen at a sector level.ConclusionQuantitative stress MBF is lower in dark rim artifacts than remote myocardium but significantly higher than in true perfusion defects. If confirmed in larger series, this approach may aid the interpretation of clinical stress perfusion exams.Trial registrationClinicalTrials.gov Identifier: NCT00027170; first posted 11/28/2001; updated 11/27/2017.

Quantitative myocardial first-pass cardiovascular magnetic resonance perfusion imaging using hyperpolarized [1-13C] pyruvate

BackgroundThe feasibility of absolute myocardial blood flow quantification and suitability of hyperpolarized [1-13C] pyruvate as contrast agent for first-pass cardiovascular magnetic resonance (CMR) perfusion measurements are investigated with simulations and demonstrated in vivo in a swine model.MethodsA versatile simulation framework for hyperpolarized CMR subject to physical, physiological and technical constraints was developed and applied to investigate experimental conditions for accurate perfusion CMR with hyperpolarized [1-13C] pyruvate. Absolute and semi-quantitative perfusion indices were analyzed with respect to experimental parameter variations and different signal-to-noise ratio (SNR) levels. Absolute myocardial blood flow quantification was implemented with an iterative deconvolution approach based on Fermi functions. To demonstrate in vivo feasibility, velocity-selective excitation with an echo-planar imaging readout was used to acquire dynamic myocardial stress perfusion images in four healthy swine. Arterial input functions were extracted from an additional image slice with conventional excitation that was acquired within the same heartbeat.ResultsSimulations suggest that obtainable SNR and B0 inhomogeneity in vivo are sufficient for the determination of absolute and semi-quantitative perfusion with ≤25% error. It is shown that for expected metabolic conversion rates, metabolic conversion of pyruvate can be neglected over the short duration of acquisition in first-pass perfusion CMR. In vivo measurements suggest that absolute myocardial blood flow quantification using hyperpolarized [1-13C] pyruvate is feasible with an intra-myocardial variability comparable to semi-quantitative perfusion indices.ConclusionThe feasibility of quantitative hyperpolarized first-pass perfusion CMR using [1-13C] pyruvate has been investigated in simulations and demonstrated in swine. Using an approved and metabolically active compound is envisioned to increase the value of hyperpolarized perfusion CMR in patients.

Multimodality Image Fusion for Coronary Artery Disease Detection: Concepts and Latest Developments.

The debate on the role of anatomy and function in the assessment of coronary artery disease has been progressing for decades. While each imaging modality brings its own strengths and weaknesses, a multimodality image fusion approach combining an anatomical acquisition with a functional one has the potential of providing all the complementary information necessary to select the proper treatment. The technology has been available to physicians for a decade, but the recent introduction of positron emission tomography-derived absolute myocardial blood flow has further advanced the case for an image fusion diagnostic approach.

Coronary flow reserve is predictive of the risk of cardiovascular death regardless of chronic kidney disease stage

Microvascular rarefaction is found in experimental uremia, but data from patients with chronic kidney disease (CKD) are limited. We therefore quantified absolute myocardial blood flow and coronary flow reserve (the ratio of peak to resting flow) from myocardial perfusion positron emission tomography scans at a single institution. Individuals were classified into standard CKD categories based on the estimated glomerular filtration rate. Associations of coronary flow reserve with CKD stage and cardiovascular mortality were analyzed in models adjusted for cardiovascular risk factors. The coronary flow reserve was significantly associated with CKD stage, declining in early CKD, but it did not differ significantly among individuals with stage 4, 5, and dialysis-dependent CKD. Flow reserve with preserved kidney function was 2.01, 2.06 in stage 1 CKD, 1.91 in stage 2, 1.68 in stage 3, 1.54 in stage 4, 1.66 in stage 5, and 1.55 in dialysis-dependent CKD. Coronary flow reserve was significantly associated with cardiovascular mortality in adjusted models (hazard ratio 0.76, 95% confidence interval: 0.63-0.92 per tertile of coronary flow reserve) without evidence of effect modification by CKD. Thus, coronary flow reserve is strongly associated with cardiovascular risk regardless of CKD severity and is low in early stage CKD without further decrement in stage 5 or dialysis-dependent CKD. This suggests that CKD physiology rather than the effects of dialysis is the primary driver of microvascular disease. Our findings highlight the potential contribution of microvascular dysfunction to cardiovascular risk in CKD and the need to define mechanisms linking low coronary flow reserve to mortality.

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)

Quantitative Assessment of Coronary Microvascular Function: Dynamic Single-Photon Emission Computed Tomography, Positron Emission Tomography, Ultrasound, Computed Tomography, and Magnetic Resonance Imaging.

A healthy, functional microcirculation in combination with nonobstructed epicardial coronary arteries is the prerequisite of normal myocardial perfusion. Quantitative assessment in myocardial perfusion and determination of absolute myocardial blood flow can be achieved noninvasively using dynamic imaging with multiple imaging modalities. Extensive evidence supports the clinical value of noninvasively assessing indices of coronary flow for diagnosing coronary microvascular dysfunction; in certain diseases, the degree of coronary microvascular impairment carries important prognostic relevance. Although, currently positron emission tomography is the most commonly used tool for the quantification of myocardial blood flow, other modalities, including single-photon emission computed tomography, computed tomography, magnetic resonance imaging, and myocardial contrast echocardiography, have emerged as techniques with great promise for determination of coronary microvascular dysfunction. The following review will describe basic concepts of coronary and microvascular physiology, review available modalities for dynamic imaging for quantitative assessment of coronary perfusion and myocardial blood flow, and discuss their application in distinct forms of coronary microvascular dysfunction.

Frequency and angiographic characteristics of coronary microvascular dysfunction in stable angina: a hybrid imaging study.

Coronary microvascular dysfunction (CMD) can cause angina in the absence of obstructive coronary artery disease (CAD). We studied the frequency and angiographic characteristics of CMD in symptomatic patients with suspected stable CAD and identified CMD as diffusely abnormal coronary vasodilator capacity by positron emission tomography (PET) perfusion imaging. We recruited prospectively 189 patients with intermediate pre-test probability of CAD who underwent coronary computed tomography angiography and quantitative 15O-water PET perfusion imaging followed by invasive coronary angiography, and assessment of fractional flow reserve when feasible. Prevalence of obstructive epicardial CAD was 37%. Absolute myocardial blood flow was diffusely reduced (<2.4 mL/g/min) within the left ventricle during adenosine stress in 32 (17%) patients. In 15 (8%) patients, this was explained by three-vessel obstructive CAD, whereas the remaining 17 (9%) were diagnosed with CMD. Of these, 2 (1% of all patients) had no coronary atherosclerosis, 5 (3% of all patients) had non-obstructive atherosclerosis, and in 10 (5% of all patients) CMD co-existed with obstructive CAD. Atypical angina or non-anginal chest pain (53%) was the most common presentation. Older age and male sex were associated with CMD, but other risk factors of CAD were equally common in patients with or without CMD. Coronary microvascular dysfunction exists in 9% of symptomatic stable patients with suspected CAD. However, the prevalence of microvascular dysfunction without any coronary atherosclerosis is low (1%) in this population.