Absolute Blood Flow Research Articles

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

THE CHANGES IN GLOBAL CORONARY BLOOD FLOW AFTER PCI EVALUATED BY CARDIOVASCULAR MAGNETIC RESONANCE IMAGING AND THEIR RELATIONSHIP WITH PHYSIOLOGICAL INDICES OBTAINED BY A PRESSURE WIRE

Few studies have documented changes in absolute coronary blood flow (CBF) after percutaneous revascularization (PCI). Phase contrast cine magnetic resonance imaging (PC-CMR) of coronary sinus (CS) is a promising approach to quantify global CBF. We aimed to assess the impact of elective PCI on global

Wide-field absolute transverse blood flow velocity mapping in vessel centerline.

We propose a wide-field absolute transverse blood flow velocity measurement method in vessel centerline based on absorption intensity fluctuation modulation effect. The difference between the light absorption capacities of red blood cells and background tissue under low-coherence illumination is utilized to realize the instantaneous and average wide-field optical angiography images. The absolute fuzzy connection algorithm is used for vessel centerline extraction from the average wide-field optical angiography. The absolute transverse velocity in the vessel centerline is then measured by a cross-correlation analysis according to instantaneous modulation depth signal. The proposed method promises to contribute to the treatment of diseases, such as those related to anemia or thrombosis.

Low-dose T1W DCE-MRI for early time points perfusion measurement in patients with intracranial tumors: A pilot study applying the microsphere model to measure absolute cerebral blood flow.

Previous studies have measured cerebral blood flow (CBF) with DSC-MRI using an "early time points" (ET) method based on microsphere theory. To develop and assess a new ET method for absolute CBF estimation using low-dose high-temporal (LDHT) T1W-DCE-MRI. Retrospective cohort study. Seven patients with sporadic vestibular schwannoma (VS) who underwent test-retest imaging; one patient with glioblastoma multiforme (GBM) imaged pretreatment; and 12 neurofibromatosis type 2 (NF2) patients undergoing bevacizumab treatment, imaged pre- and 90 days posttreatment. LDHT-DCE-MRI was performed at 1.5 and 3.0T, using 3D spoiled gradient echo with phase cycling. DSC-MRI performed in one patient, using 3D echo-shifted multi-shot echo-planar imaging (PRESTO) at 3T. Through Monte Carlo simulations, CBF estimation using three newly developed average contrast agent concentration (AC) -based methods (ACrPK, ACrMG, ACcomb), was compared against conventional maximum gradient (MG) approaches, at varying Rician noise levels. Reproducibility and applicability of the ACcomb method was assessed in our sporadic-VS/GBM/NF2 patient cohort, respectively. Reproducibility was measured using test-retest coefficient of variation (CoV). Pre- and posttreatment CBF values were compared using paired t-test with Bonferroni correction. Monte Carlo stimulations demonstrated that AC-based methods, particularly ACcomb, offered superior accuracy to conventional MG approaches. Overall test-retest CoV using the ACcomb method was 5.76 in normal-appearing white matter (NAWM). The new ACcomb method produced gray matter/white matter CBF estimates in the NF2 patient cohort of 55.9 ± 13.9/25.8 ± 3.5 on day 0; compared with 155.6 ± 17.2/128.4 ± 29.1 for the classical MG method. There was a moderate (10% using ACcomb and ACrPK) increase in CBF of NAWM 90 days post therapy (P = 0.03 and 0.005). Our new AC-based method of CBF estimation offers excellent reproducibility, and displays more accuracy in both Monte Carlo analysis and clinical data application, than conventional MG-based approaches. 1 Technical Efficacy: Stage 4 J. MAGN. RESON. IMAGING 2018;48:543-557.

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.

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.

The optimal intestinal segment length for experimental size-mismatched intestinal transplantation: Defining the maximum length with the lowest blood flow needs in a porcine model.

Transplanted Intestinal Segments (IS) must match the perfusion capacities of the recipient. This can be challenging during a size-mismatched SBTX. In this study, we defined the maximum IS length with lowest blood flow needs in a porcine model by evaluating the physiological perfusion rates of different IS lengths. Blood flow in the SMA, aorta segment four, and general circulatory parameters were monitored before and after sequential intestinal resection. IS lengths of 30cm, 60cm, 120cm, and 300cm (n=8 each) were compared. The IS blood flow requirements increased with IS length (30cm: 19.5±3.4mL/min; 60cm: 16.9±6.7mL/min; 120cm: 34.9±8.5mL/min; 300cm: 62.9±11.6mL/min). Absolute IS blood flow (P=.004), percentage IS blood flow uptake from the SMA (P=.001), and percentage IS blood flow uptake from the aorta (P=.005) increased significantly between 60cm and 120cm. We concluded that 60cm was the maximum IS length before blood flow demands significantly increased in a porcine model.

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.

Neuroprotection Mediated by Upregulation of Endothelial Nitric Oxide Synthase in Rho-Associated, Coiled-Coil-Containing Kinase 2 Deficient Mice.

Rho-associated kinases (ROCK1 and ROCK2) are important regulators of the actin cytoskeleton and endothelial nitric oxide synthase (eNOS). Because the phosphorylation of eukaryotic elongation factor-1A1 (eEF1A1) by ROCK2 is critical for eNOS expression, we hypothesized that this molecular pathway may play a critical role in neuroprotection following focal cerebral ischemia.Methods and Results:Adult male wild-type (WT) and mutant ROCK2 and eNOS-/-mice were subjected to middle cerebral artery occlusion (MCAO), and cerebral infarct size, neurological deficit and absolute cerebral blood flow were measured. In addition, aortic endothelium-dependent response to acetylcholine, NG-nitro-L-arginine methyl ester (L-NAME) and sodium nitroprusside were assessed ex vivo. Endothelial cells from mouse brain or heart were used to measure eNOS and eEF1A activity, as well as NO production and eNOS mRNA half-life. In global hemizygous ROCK2+/-and endothelial-specific EC-ROCK2-/-mice, eNOS mRNA stability and eNOS expression were increased, which correlated with enhanced endothelium-dependent relaxation and neuroprotection following focal cerebral ischemia. Indeed, when ROCK2+/-mice were place on an eNOS-/-background, the neuroprotective effects observed in ROCK2+/-mice were abolished. These findings indicate that the phosphorylation of eEF1A1 by ROCK2 is physiologically important for eNOS expression and NO-mediated neuroprotection, and suggest that targeting endothelial ROCK2 and eEF1A may have therapeutic benefits in ischemic stroke and cardiovascular disease.

Compact, multi-exposure speckle contrast optical spectroscopy (SCOS) device for measuring deep tissue blood flow.

Speckle contrast optical spectroscopy (SCOS) measures absolute blood flow in deep tissue, by taking advantage of multi-distance (previously reported in the literature) or multi-exposure (reported here) approach. This method promises to use inexpensive detectors to obtain good signal-to-noise ratio, but it has not yet been implemented in a suitable manner for a mass production. Here we present a new, compact, low power consumption, 32 by 2 single photon avalanche diode (SPAD) array that has no readout noise, low dead time and has high sensitivity in low light conditions, such as in vivo measurements. To demonstrate the capability to measure blood flow in deep tissue, healthy volunteers were measured, showing no significant differences from the diffuse correlation spectroscopy. In the future, this array can be miniaturized to a low-cost, robust, battery operated wireless device paving the way for measuring blood flow in a wide-range of applications from sport injury recovery and training to, on-field concussion detection to wearables.

Three-dimensional imaging of absolute blood flow velocity and blood vessel position under low blood flow velocity based on Doppler signal information included in scattered light from red blood cells

The development of a system for in vivo visualization of occluded distal blood vessels for diabetic patients is the main target of our research. We herein describe two-beam multipoint laser Doppler velocimetry (MLDV), which measures the instantaneous multipoint flow velocity and can be used to observe the blood flow velocity in peripheral blood vessels. By including a motorized stage to shift the measurement points horizontally and in the depth direction while measuring the velocity, the path of the blood vessel in the skin could be observed using blood flow velocity in three-dimensional space. The relationship of the signal power density between the blood vessel and the surrounding tissues was shown and helped us identify the position of the blood vessel. Two-beam MLDV can be used to simultaneously determine the absolute blood flow velocity distribution and identify the blood vessel position in skin.

Measurement of the absolute velocity of blood flow in early-stage chick embryos using spectral domain optical coherence tomography.

Doppler optical coherence tomography (OCT) is a noninvasive imaging modality that provides quantitative flow information with high spatial and temporal resolution. However, it is only sensitive to the flow velocity vector parallel to the incident beam. To calculate the absolute velocity, it is necessary to obtain the angle between the incident beam and flow field. In this paper, we describe a practical method to measure the Doppler angle based on the structural information of blood vessels extracted from spectral domain OCT images. In this method, a normal sectional scan of the vessel is performed where the probe beam is perpendicular to the vessel. Next, the axial diameter (Z direction) of the vessel (DA) was measured in the acquired image. For a certain scan in which the probe beam is oblique to the blood vessel, the axial diameter of the vessel (DA') can be measured. Thus, the Doppler angle can be calculated depending on the ratio of DA and DA', and absolute blood flow was determined. We validate this method in a capillary tube as well as in large blood vessels of early-stage chick embryos. This technique is suitable for early-stage embryo blood-flow measurement because most of the blood vessels are easily differentiated from the transparent surrounding structures during that time.

Skeletal muscle protein accretion rates and hindlimb growth are reduced in late gestation intrauterine growth-restricted fetal sheep.

Adults who were affected by intrauterine growth restriction (IUGR) suffer from reductions in muscle mass, which may contribute to insulin resistance and the development of diabetes. We demonstrate slower hindlimb linear growth and muscle protein synthesis rates that match the reduced hindlimb blood flow and oxygen consumption rates in IUGR fetal sheep. These adaptations resulted in hindlimb blood flow rates in IUGR that were similar to control fetuses on a weight-specific basis. Net hindlimb glucose uptake and lactate output rates were similar between groups, whereas amino acid uptake was significantly lower in IUGR fetal sheep. Among all fetuses, blood O2 saturation and plasma glucose, insulin and insulin-like growth factor-1 were positively associated and norepinephrine was negatively associated with hindlimb weight. These results further our understanding of the metabolic and hormonal adaptations to reduced oxygen and nutrient supply with placental insufficiency that develop to slow hindlimb growth and muscle protein accretion. Reduced skeletal muscle mass in the fetus with intrauterine growth restriction (IUGR) persists into adulthood and may contribute to increased metabolic disease risk. To determine how placental insufficiency with reduced oxygen and nutrient supply to the fetus affects hindlimb blood flow, substrate uptake and protein accretion rates in skeletal muscle, late gestation control (CON) (n=8) and IUGR (n=13) fetal sheep were catheterized with aortic and femoral catheters and a flow transducer around the external iliac artery. Muscle protein kinetic rates were measured using isotopic tracers. Hindlimb weight, linear growth rate, muscle protein accretion rate and fractional synthetic rate were lower in IUGR compared to CON (P<0.05). Absolute hindlimb blood flow was reduced in IUGR (IUGR: 32.9±5.6mlmin-1 ; CON: 60.9±6.5mlmin-1 ; P<0.005), although flow normalized to hindlimb weight was similar between groups. Hindlimb oxygen consumption rate was lower in IUGR (IUGR: 10.4±1.4μmolmin-1 100g-1 ; CON: 14.7±1.3μmolmin-1 100g-1 ; P<0.05). Hindlimb glucose uptake and lactate output rates were similar between groups, whereas amino acid uptake was lower in IUGR (IUGR: 1.3±0.5μmolmin-1 100g-1 ; CON: 2.9±0.2μmolmin-1 100g-1 ; P<0.05). Blood O2 saturation (r2 =0.80, P<0.0001) and plasma glucose (r2 =0.68, P<0.0001), insulin (r2 =0.40, P<0.005) and insulin-like growth factor (IGF)-1 (r2 =0.80, P<0.0001) were positively associated and norepinephrine (r2 =0.59, P<0.0001) was negatively associated with hindlimb weight. Slower hindlimb linear growth and muscle protein synthesis rates match reduced hindlimb blood flow and oxygen consumption rates in the IUGR fetus. Metabolic adaptations to slow hindlimb growth are probably hormonally-mediated by mechanisms that include increased fetal norepinephrine and reduced IGF-1 and insulin.

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.

The role of three-dimensional pseudo-continuous arterial spin labelling in grading and differentiating histological subgroups of meningiomas

To evaluate the usefulness of pseudo-continuous arterial spin labelling (pCASL) imaging in grading and differentiating histological subtypes of meningiomas. In this prospective study, conventional magnetic resonance imaging (MRI) with contrast-enhanced T1-weighted images and pCASL were acquired with a 3 T MRI system before surgery in 125 consecutive patients with suspected meningiomas. Finally, the perfusion parameters were collected from 84 grade I and 23 grade II meningiomas. On the pCASL perfusion map, the mean absolute cerebral blood flow (CBF) values from the meningioma (CBFtumour), peritumoural oedema (CBFPTO), white matter of contralateral centrum semi-ovale (CBFwm) and normal grey matter (CBFgm) were calculated. Additionally, the associations of these perfusion parameters with the value of ki-67 index were analysed. The CBFwm value correlated negatively with the largest diameter of the tumour, which limited its usage as a reference for ratio calculation. The CBFtumour values of grade II and grade I meningiomas did not differ significantly: 137.36±71.85 ml/min/100 g versus 123.58±135.80 ml/min/100 g (p=0.641). The CBFPTO value was higher for grade II meningioma as than for grade I meningiomas: 30.30±15.56 ml/min/100 g versus 22.33±9.87 ml/min/100 g (p=0.037). The CBFtumour value was highest in angiomatous meningioma and lowest in fibrous meningioma, thus enabling the differentiation of subtypes of meningioma. The CBFtumour value did not correlate with the ki-67 index of meningioma. The CBFPTO value, rather than the CBFtumour value, from pCASL imaging may serve as a key factor in distinguishing different grades of meningiomas. Moreover, angiomatous meningiomas and fibrous meningiomas can be identified by CBFtumour value.

Effect of Elective Percutaneous Coronary Intervention on Hyperemic Absolute Coronary Blood Flow Volume and Microvascular Resistance.

The hemodynamics involved in the relationship between absolute coronary blood flow (ABF) volume and myocardial resistance (MR) are complex, and the effect of percutaneous coronary intervention (PCI) on their changes remains unclear. The aim of this study was to investigate the differences in hyperemic ABF and MR before and after elective PCI using a thermodilution method. We investigated 28 vessels (right coronary artery, 9; left anterior descending coronary artery, 18; left circumflex coronary artery, 1) from 28 patients with stable angina pectoris undergoing elective PCI. ABF was measured pre- and post-PCI using a pressure-temperature sensor-equipped wire, based on a thermodilution method with a continuous saline infusion of 20 mL/min through a proximally located microcatheter with an end-hole in the target vessel. MR equals distal coronary perfusion pressure divided by ABF at maximal hyperemia. Conventional fractional flow reserve was also measured pre- and post-PCI. Fractional flow reserve increased significantly after PCI (from 0.70 [0.65-0.75] to 0.88 [0.85-0.95]) in all examined territories. ABF also increased significantly (from 137.8 mL/min [86.3-180.8 mL/min] to 173.3 mL/min [137.9-234.3 mL/min] ; increase: 52.8 mL/min [9.7-80.8 mL/min]) while MR decreased in 11 vessels and increased in 17. No significant relationship was detected between these increases in fractional flow reserve and ABF. Both pre- and post-PCI MR distributed in a wide range, and there was a significant relationship between pre-PCI MR and the increase in ABF (r=0.44; P=0.02) although no significant change in MR was observed between pre- and post-PCI (P=0.37). Direct measurement of ABF and MR using thermodilution method offers a feasible approach that could shed a light on previously unclear aspects of coronary hemodynamics.

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)