Rest Flow Research Articles

Endogen microvascular dysfunction is associated with worse outcomes in heart transplantation

Abstract Background Cardiac allograft vasculopathy (CAV) affects the health of both epicardial and microvascular blood vessels in heart transplants. Coronary microvascular dysfunction (CMD) has been associated with poor outcomes in the non-transplant population. Two patterns of microvascular dysfunction have been characterized, classical (low stress flow) and endogen (high rest flow). Whether these patterns of microvascular dysfunction are associated with outcomes in the transplant population has not been thoroughly evaluated. Purpose The purpose of the study was to assess the relationship between microvascular dysfunction and adverse outcomes in patients with heart transplants. Methods Patients with no history of angiographic CAV who underwent positron emission tomography myocardial perfusion imaging and were found to have normal perfusion (summed stress score = 0) were included in the study. Patients were then classified by microvascular dysfunction: normal (flow reserve ≥ 2.0) versus abnormal (flow reserve <2.0). Patients were further subclassified based on pattern of microvascular dysfunction, classical (stress myocardial flow <1.7 mL/min/g) and endogen (stress myocardial flow ≥1.7 mL/min/g). The two primary outcomes were all-cause mortality and a composite of death, heart failure hospitalization, acute coronary syndrome, and revascularization. Kaplan-Meier survival and Cox proportional regression were used to assess the relationship between microvascular function and outcomes. Results In total, 359 patients were enrolled in the study, of which 29 (8%) had classical CMD and 78 (22%) had endogen CMD. Patients with endogen CMD were more likely to be women (46%) compared to 31% for normal microvascular function and 24% for classical CMD. During a median follow up period of 2.0 years (Q1 1.7, Q3 2.3), 36 patients had an adverse event and 19 patients died. Endogen CMD was associated with a significantly higher risk of both the composite outcome, HR 2.30 (1.15 – 4.61), and all-cause mortality, 4.19 (1.64 – 10.73). Classical CMD was not associated with either the composite outcome, HR 0.88 (0.20 – 3.84) or death, HR 1.02 (0.12 – 8.33), however assessment of classical CMD was limited by small sample size. Conclusions Endogen-type CMD is associated with worse intermediate-term outcomes in transplant patients compared to normal microvascular function and classical-type CMD, although comparison to classical-type CMD was limited by small sample size.Table 1:DemographicsFigure 1:KM Survival Curves

Effect of active and passive techniques used in thromboembolic prophylaxis on venous flow velocity in the post-procedure period.

Studies have shown that using mechanical thromboembolic prophylaxis methods speeds up venous flow and decreases stasis. These studies examine the post-intervention period of 1-10min. The length of the effect of procedures to raise venous flow velocity cannot be determined by clinical trials. To apply mathematical techniques to estimate how long mechanical thromboembolism prophylaxis procedures will increase venous flow rate. In the survey, we examined 25 persons (poststroke patients), with an average age of 57.2 ± 6.3 years. Regarding the proportion of genders, 13 (52%) participants were male and 12 (48%) female. The peak venous blood flow velocity was measured with a HADECO BIDOP ES-100V II type Doppler ultrasound device, using an 8MHz head, in the femoral vein, at the level of the hip joint. We estimated the change of the venous blood flow velocity from the available sampled data using the method of least squares. For the calculations, we used Microsoft Excel, version Mac Excel 2019. The decrease in peak venous flow velocity can be approximated by a logarithm function. Mathematical calculations show that after active thromboembolic prophylaxis interventions, resting venous flow velocity is restored at 26.8min on the intact limb and 85.1min on the hemiparetic side. Resting flow velocity is restored in 131.9min after passive mobilization of the hemiparetic side and in 137.7min after the consensual effect. An elementary mathematical function can be used to estimate the time to recovery of peak venous flow velocity to resting state from measurements taken 15min after the intervention. Active and passive mechanical thromboembolic prophylaxis after the intervention has a longer-term effect on venous flow velocity.

Abstract 14679: Microcirculatory Flow and Resistance at Rest and Hyperemia in Relation to Major Adverse Cardiovascular Events in Chronic Coronary Syndrome

Background: The prognostic implications of coronary microvascular dysfunction in an all-comer cohort with chronic coronary syndrome (CCS) are not known. Aim: To investigate the association of baseline resistance index (BRI), index of microcirculatory resistance (IMR), and thermodilution-derived resting- and hyperemic flow velocities (RFV and HFV) with the primary composite endpoint consisting of all-cause mortality, incident myocardial infarction (MI) or hospitalization due to congestive heart failure (CHF) in CCS. Methods: CCS patients undergoing elective coronary angiography (CA) were included. Measurements of corrected IMR, BRI and mean transit time at baseline (Tmn base ) and during hyperemia (Tmn hyp ) were obtained in the LAD. RFV and HFV were calculated as 1/Tmn base and 1/Tmn hyp , respectively. Cox-regression was performed and Kaplan-Meier plots were constructed. Results: We included 503 patients before the coronary anatomy was known and thermodilution measurements in the LAD were obtained in 413 patients. Median age was 68 (IQR 61-74), 127 (25%) were women and 151 (37%) had a flow-limiting epicardial lesion in the LAD. Median follow-up was 5.3 years (IQR 3.0-6.6) and there were 57 events. Log 10 BRI was inversely associated with the primary endpoint before and after fractional flow reserve (FFR) adjustments (HR 0.64 [95% CI 0.42 - 0.97]; Figure 1A). Log 10 IMR was not associated with the primary endpoint (HR 0.94 [95% CI 0.61 - 1.5]; Figure 1B). Log 10 RFV was associated with the primary endpoint before and after FFR- adjustment (HR 1.8 [95% CI 1.2 - 2.7]) whereas log 10 HFV was not (HR 1.2 [95% CI 0.75-1.8]). Conclusion: Low microcirculatory resting resistance and high coronary resting flow velocity in the LAD, indicating impaired autoregulation, were associated with all-cause death, MI and/or CHF in CCS whereas hyperemic microcirculatory resistance and flow were not. Resting flow indices can be used for risk evaluation in patients with CCS undergoing CA. .

Flow Behaviour and Wall Shear Stress Derivatives in Abdominal Aortic Aneurysm Models: A Detailed CFD Analysis into Asymmetry Effect

Assessing the risk of rupture is extremely important to reduce the mortality of the abdominal aortic aneurysm (AAA). Current clinical guidelines suggest considering the maximum diameter as a criterion for planning and surgical intervention; however, this approach is too simplistic and overlooks other morphological parameters that are associated with the risk of rupture. The aim of this paper is to study the thrombogenicity and to predict the risk of AAA rupture by taking into consideration the geometrical asymmetry of the aneurysm, studying its effect on blood flow behaviour and vortical structure, spatiotemporal distribution of wall shear stresses (WSS), and their related parameters. To show the effect of asymmetry on blood flow dynamics and hemodynamic forces, five virtual models were constructed using five values of geometrical asymmetry ratio β ranging from β=0.2 (asymmetric model; AM) to β=1 (symmetric model; SM). Simulations were run for each geometry under transient physiological flow conditions using finite volume discretization. Resting flow rate was investigated in these models and our results demonstrate that the asymmetry of the aneurysm has a clear effect on the flow behaviour, and consequently on WSS distribution, oscillatory shear index (OSI) and time averaged wall shear stress (TAWSS). Furthermore, these preliminary findings suggest that thrombus formation and rupture risk are more probable in an asymmetric abdominal aortic aneurysm.

Smart Sharing Plan: The Key to the Water Crisis

Over the years, the Colorado River has become inadequate for development due to natural factors and human activities. The hydroelectric facilities in Lake Mead and Lake Powell are also not fully utilized. Downstream, Mexico is also involved in the competition for water. The resulting allocation of water and electricity resources and sustainable development are hanging over our heads and waiting to be solved. In this work, a simplified Penstock Dam model and a Distance Decay model are designed based on publicly available data, and a Multi-attribute Decision model for hydropower based on the Novel Technique for Order Preference by Similarity to an Ideal Solution method is proposed. In addition, an Improved Particle Swarm Optimization model is proposed by adding oscillation parameters. The Mexican equity problem is also explored. The theoretical results show that the average error of the Penstock Dam model is 3.2%. The minimum water elevation requirements for Lake Mead and Lake Powell are 950 ft and 3460 ft, respectively; they will not meet demand in 2026 and 2027 without action, and they will require the introduction of 3.69×1010 m3 and 2.08×109 m3 water in 2027 and 2028, respectively. The solution shows that the net profit for the United States is greatest when 38.6% of the additional water is used for general purposes, 47.5% is used for power generation, and the rest flows to Mexico. A final outlook on the sustainability of the Colorado River is provided.

Laser Doppler flowmetry evaluation of skin microvascular endothelial function in patients with metabolic syndrome.

Metabolic syndrome (MetS) is associated with high cardiovascular morbidity and mortality, and endothelial dysfunction is an early pathogenetic event in the MetS. Lifestyle changes and pharmacological intervention might partly restore endothelial function in MetS. Whereas an optimal non-invasive test for endothelial dysfunction is still being sought, the aim of this study was to assess the relationship between changes in skin microvascular endothelial function, detected by Laser Doppler flowmetry, and cardiovascular risk factors (CVRFs) of patients with MetS. 3081 patients (1865 women and 1216 men, mean age 53±6years) with MetS were enrolled in the study, which was conducted during the period of 2010-2014 at Vilnius University Hospital Santaros Klinikos. Skin microvascular endothelial function was evaluated using the Laser Doppler flowmetry in combination with the post-occlusive reactive hyperaemia test. The percentage change of flow from peak to the rest flow (PF-RF) was calculated and used as the main measure of endothelial function. The study showed that decrease in flow-mediated dilatation reflected by PF-RF was associated with increased triglycerides (p=0.002), male sex (p<0.001), and diabetes (p=0.002). Patients with quite a few CVRFs (body mass index ≥25kg/m2, smoking, diabetes, arterial hypertension, a positive history of dyslipidaemia) had significantly lower PF-RF score than patients only with one of these risk factors (p<0.001). Changes in skin microvascular endothelial function are significantly associated with most CVRFs and depend on the number of CVRFs.

Effects of regular physical exercise on skin blood flow and cardiovascular risk factors in overweight and obese subjects

Objective: it is well known that low omentin levels and reduced bioavailability of nitric oxide (NO) are outgrowth of obesity. Besides, in obese subjects, microvascular dysfunction can be an initial stage of cardiovascular diseases. This situation can be evaluated with skin laser–Doppler flowmetry (LDF).Methods: in this study we investigated the effects of 12 weeks moderate physical exercise on microvascular reactivity and plasma levels of omentin and NO in 25 overweight and obese subjects. Control group was composed of 28 sedentary participants who were neither obese nor overweight. Microvascular reactivity was handled by measurement of skin blood flow from the ring finger of the right hand with LDF, which is a non–invasive method for evaluation. With this method, it was aimed to examine the post–occlusive reactive hyperemia response of the patients. None of the participants in both groups have never followed a regular exercise schedule in their life span.Results: with regular exercise, there was a statistically significant decrease in glucose (p=0.008), cholesterol (p=0.05), and triglyceride (p=0.048) levels, while body mass index, high–density lipoprotein, and low–density lipoprotein levels did not change significantly in overweight/obese group. Also, the omentin level significantly increased (p=0.01), but NO level did not change significantly. Moreover, the amount of change in omentin and NO levels measured before and after the physical exercise were significantly correlated (r=0.57). Considering the microcirculation, rest flow (p=0.001) and peak flow value of LDF (p=0.001) increased after the physical exercise.Conclusion: our study shows that moderate physical exercise affects microvascular reactivity and plasma levels of omentin in overweight and obese subjects.

Clinically viable myocardial CCTA segmentation for measuring vessel-specific myocardial blood flow from dynamic PET/CCTA hybrid fusion

BackgroundPositron emission tomography (PET)-derived LV MBF quantification is usually measured in standard anatomical vascular territories potentially averaging flow from normally perfused tissue with those from areas with abnormal flow supply. Previously we reported on an image-based tool to noninvasively measure absolute myocardial blood flow at locations just below individual epicardial vessel to help guide revascularization. The aim of this work is to determine the robustness of vessel-specific flow measurements (MBFvs) extracted from the fusion of dynamic PET (dPET) with coronary computed tomography angiography (CCTA) myocardial segmentations, using flow measured from the fusion with CCTA manual segmentation as the reference standard.MethodsForty-three patients’ 13NH3 dPET, CCTA image datasets were used to measure the agreement of the MBFvs profiles after the fusion of dPET data with three CCTA anatomical models: (1) a manual model, (2) a fully automated segmented model and (3) a corrected model, where major inaccuracies in the automated segmentation were briefly edited. Pairwise accuracy of the normality/abnormality agreement of flow values along differently extracted vessels was determined by comparing, on a point-by-point basis, each vessel’s flow to corresponding vessels’ normal limits using Dice coefficients (DC) as the metric.ResultsOf the 43 patients CCTA fully automated mask models, 27 patients’ borders required manual correction before dPET/CCTA image fusion, but this editing process was brief (2–3 min) allowing a 100% success rate of extracting MBFvs in clinically acceptable times. In total, 124 vessels were analyzed after dPET fusion with the manual and corrected CCTA mask models yielding 2225 stress and 2122 rest flow values. Forty-seven vessels were analyzed after fusion with the fully automatic masks producing 840 stress and 825 rest flow samples. All DC coefficients computed globally or by territory were ≥ 0.93. No statistical differences were found in the normal/abnormal flow classifications between manual and corrected or manual and fully automated CCTA masks.ConclusionFully automated and manually corrected myocardial CCTA segmentation provides anatomical masks in clinically acceptable times for vessel-specific myocardial blood flow measurements using dynamic PET/CCTA image fusion which are not significantly different in flow accuracy and within clinically acceptable processing times compared to fully manually segmented CCTA myocardial masks.

Effects of high oxygen tension on healthy volunteer microcirculation.

Previous studies have highlighted hyperoxia-induced microcirculation modifications, but few have focused on hyperbaric oxygen (HBO) effects. Our primary objective was to explore hyperbaric hyperoxia effects on the microcirculation of healthy volunteers and investigate whether these modifications are adaptative or not. This single centre, open-label study included 15 healthy volunteers. Measurements were performed under five conditions: T0) baseline value (normobaric normoxia); T1) hyperbaric normoxia; T2) hyperbaric hyperoxia; T3) normobaric hyperoxia; T4) return to normobaric normoxia. Microcirculatory data were gathered via laser Doppler, near-infrared spectroscopy and transcutaneous oximetry (PtcO₂). Vascular-occlusion tests were performed at each step. We used transthoracic echocardiography and standard monitoring for haemodynamic investigation. Maximal alterations were observed under hyperbaric hyperoxia which led, in comparison with baseline, to arterial hypertension (mean arterial pressure 105 (SD 12) mmHg vs 95 (11), P < 0.001) and bradycardia (55 (7) beats·min⁻¹ vs 66 (8), P < 0.001) while cardiac output remained unchanged. Hyperbaric hyperoxia also led to microcirculatory vasoconstriction (rest flow 63 (74) vs 143 (73) perfusion units, P < 0.05) in response to increased PtcO₂ (104.0 (45.9) kPa vs 6.3 (2.4), P < 0.0001); and a decrease in laser Doppler parameters indicating vascular reserve (peak flow 125 (89) vs 233 (79) perfusion units, P < 0.05). Microvascular reactivity was preserved in every condition. Hyperoxia significantly modifies healthy volunteer microcirculation especially during HBO exposure. The rise in PtcO₂ promotes an adaptative vasoconstrictive response to protect cellular integrity. Microvascular reactivity remains unaltered and vascular reserve is mobilised in proportion to the extent of the ischaemic stimulus.

Abstract 11515: Noninvasive Quantitation of Coronary Collateral Flow Capacity in Patients with Chronic Total Occlusion Treated with External Counter Pulsation: Dobutamine Compared with Vasodilator Stress Pet Identifies Collaterogenesis

Introduction: FDA approved external counterpulsation (ECP) improves coronary collateral flow index measured invasively, using intracoronary wedge pressure beyond a severe stenosis. However, there is presently no noninvasive method to measure coronary collateral flow capacity (CCFC), in patients with total coronary occlusion (CTO). Hypothesis: CCFC can be measured noninvasively by comparing the improvement in flow in the ischemic bed beyond CTO, using dobutamine stress (DBT), which supports supply side pressure, compared with vasodilator stress (DIP), which lowers supply side pressure, causing coronary steal. Methods: Seven patients with CTO were treated with 35 sessions of ECP, and studied with both DIP and DOB stress PET myocardial perfusion imaging. Coronary flow capacity (CFC), which integrates absolute rest and stress flow with coronary flow reserve on a per pixel basis, was measured objectively with FDA approved HeartSee software. Results: As shown in the Table, all patients demonstrated a decrease in the size of the ischemic zone at risk, defined as moderate or severely reduced CFC, when CFC with DIP was compared with DOB: 28% LV mass vs. 5%; p &amp;lt 0.01. Five of 7 patients also demonstrated significant improvement in global CFC by Kolmogorov-Smirnoff analysis. Absolute stress flow into the ischemic zone improved significantly in all ECP treated patients during demand ischemia compared with vasodilator stress (1.9 vs. 1 ml/min/g; p &amp;lt 0.01). One of the two patients who did not improve global CFC, despite ECP treatment, underwent coronary arteriography demonstrating a new flow limiting stenosis in the supply side vessel, which was successfully stented. Conclusion: ECP treatment is associated with improved coronary collateralization in patients with CTO, which can be identified noninvasively with quantitative PET myocardial perfusion imaging.

Visualization of two-phase refrigerant flow in the inlet header of brazed plate heat exchangers and its effect on distribution

• Two-phase flow visualization is achieved by a clear window on the inlet header. • Flow regime in the inlet header is periodic and one cycle has two or three stages. • Flow regime in the inlet header significantly affects the two-phase distribution. • Effects of mass flux, inlet vapor quality, and the number of plates are examined. This paper presents an experimental study of two-phase R134a flow in the inlet header of brazed plate heat exchangers and its effect on flow distribution among the channels. Visualization of the two-phase flow is accomplished through a 3-D printed transparent window on the inlet header of the heat exchangers. The two-phase flow distribution among channels is quantified based on infrared images of the heat exchanger sidewalls. At the test conditions, the observed flow regimes in the inlet header are periodic and two or three stages are identified in one cycle: top corner vapor flow, vapor jet flow, and (conditional) liquid blockage flow. Among them, the top corner vapor flow affects the distribution most, in which the vapor refrigerant is mainly present at the top corner of the header and branches out through the first several channels, leaving the liquid refrigerant to occupy the rest flow area of the inlet header and present a single-phase like distribution profile. When the inlet vapor quality increases, the distribution of the liquid refrigerant is improved since the vapor refrigerant can reach more downstream channels to help balance the total pressure drop. With the mass flux increases, the maldistribution caused by the header induced pressure drop is more significant, which compromises the benefit brought by the higher vapor momentum. When the number of plates is increased, the liquid refrigerant distribution is worse due to an increased pressure drop in the headers.

Pore-Scale Investigation of the Effect of Micro-Porous Layer on Water Transport in Proton Exchange Membrane Fuel Cell

A 3D lattice Boltzmann model is developed to simulate the pore-scale two-phase flow in the porous transport layer (PTL). The PTL, composed of the gas diffusion layer (GDL) and the micro porous layer (MPL), is stochastically reconstructed and validated by comparing the pore size distribution (PSD) with experimental data. This work focuses on the effect of MPL on liquid water transport in terms of hydrophobicity, PSD and structure. It is found that more hydrophobic material and smaller pore size apply higher local capillary force against the water transport. Water can only break through the crack-free MPL under an extremely high inlet pressure (about 400 kPa). Under the real operating conditions of a fuel cell, the PTL with single GDL suffers flooding with a low fraction of dry pore. With the presence of cracked MPL, the fraction of dry pore increases significantly since a large amount of water is constrained in the electrode and only the rest flows into the GDL through the cracks, which can keep the membrane hydrated and avoid flooding. Finally, a systematically designed PTL is proposed with uniformly distributed perforations, which can automatically balance the water content and further optimize the proton conductivity and reactant transport, simultaneously.

Micro- and macrocirculatory, and biohumoral changes after a month of physical exercise in patients with intermittent claudication

We studied 15 subjects with intermittent claudication, classed as stage II according to Leriche-Fontaine. The patients were subjected to laser Doppler flowmetry, strain gauge plethysmography, Doppler velocimetry, and blood sampling, in basal conditions and after one month of physical training. Symptom-free walking distance at the end of the training period showed a significant increase, while there was no major change in maximal walking distance or the Windsor index. Laser Doppler flowmetry showed no significant change in cutaneous blood flow at rest, after the month of physical training. On the other hand, strain gauge plethysmography showed a significant decrease in rest flow at the end of the training period, while peak flow of postischemic hyperemia did not change appreciably. Biohumoral evaluations showed a significant decrease of white blood cell count, triglycerides and uric acid. Platelet count, prothrombin time, aPTT and plasminogen were unchanged. On the other hand, we recorded a small, but significant, rise of fibrinogen. Our study confirmed the importance of scheduled physical activity in the patient with intermittent claudication, showing that clinical improvement is not accompanied by an increase in the circulatory reserve. The unchanged levels of plasminogen suggest that the fibrinolytic activity does not vary significantly after a course of physical exercise.

Reproducibility of Novel Indices of Reactive Hyperemia Using Laser Speckle Contrast Imaging

Post‐occlusive reactive hyperemia (PORH) is an indicator of microvascular function, but lack of standardization and reliability of measurement have limited its use clinically. The purpose of this study was to assess the intra‐ and inter‐day reliability of conventional and novel parameters of PORH using laser speckle contrast imaging (LSCI). Seventeen healthy adults (age = 24±3 years) completed three PORH bouts over two randomly assigned lab visits that were interspaced by 4–14 days. LSCI region of interest was a standardized 10 cm region below the antecubital fossa on the dominant ventral forearm. A 5‐min brachial artery occlusion period induced by inflating an arm cuff to 200 mmHg, preceded a 4‐min hyperemic period. LSCI flux was expressed as cutaneous vascular conductance (CVC; flux/mean arterial pressure). Reliability and reproducibility were assessed using intraclass correlation (ICC) and coefficient of variation (CV). Maximal flow (peak) and area under the curve (AUC) normalized to zero perfusion showed intra‐ and inter‐day reliability of ICC &gt; 0.70. Inter‐day ICC was lower when AUC was expressed as a function of resting flow (ICC=0.50) or biological zero (ICC=0.66). Time to maximal flow (TMF) had lower intra‐day (CV=12%) and inter‐day (CV=18%) reproducibility. When representing velocity (overshoot rate of change, ORC) within defined time ranges (5s, 10s, 15s, and 20s into hyperemia) as a piecewise function, the inter‐day reproducibility was &lt;11%. Thus, depending on data normalization, PORH using LSCI is a reliable method to assess microvascular function. TMF should be interpreted with caution, but an alternative temporal index may be the ORC.Support or Funding InformationThis research did not receive any specific grant from funding agencies in the public, commercial, or non‐profit sectors.Commonly examined post‐occlusive reactive hyperemia parameters are illustrated. Resting flow (RF), maximal flow (MF), time to maximal flow (TMF), amplitude of the MF normalized to RF and BZ (AMPRF and AMPBZ) and 4‐min post cuff‐deflation area under hyperemic curve (4‐min AUC) normalized to zero perfusion are shown. Time = 0 corresponds to cuff deflation. Magnified tracing at the top right shows the hyperemic response 30s post‐cuff deflation.Figure 1 Statistics for the PORH parameters are shown as mean ± SD, ICC, 95% limits of agreement, and coefficient of variation for the three PORH responses (VA, VB1, VB2). ICC values less than 0.5, between 0.5–0.75, between 0.75–0.9, and above 0.9 are classified as having poor, moderate, good, and excellent reliability. CV values less than 10%, between 10–25%, and above 25% are considered having good, moderate, and poor reproducibility. Descriptive Statistics (CVC) Reproducibility Statistics (CVC) Mean ± SD INTRADAY (VB1 &amp; VB2) INTERDAY (VA &amp; VB1) VA VB1 VB2 ICC (LOA) CV (%) ICC (LOA) CV (%) RF 0.62 ± 0.17 0.62 ± 0.14 0.60 ± 0.15 0.89 (0.73, 0.96) 6.47 0.89 (0.72, 0.96) 6.72 MF 2.41 ± 0.70 2.32 ± 0.56 2.35 ± 0.73 0.88 (0.70 0.95) 5.13 0.77 (0.48,0.91) 9.49 TMF 19.3 ± 5.68 19.0 ± 6.82 18.9 ± 5.11 0.65 (0.25, 0.86) 11.71 0.52 (0.06, 0.80) 17.75 4‐min AUC 282 ± 88.5 274 ± 70.4 262 ± 67.2 0.93 (0.79, 0.97) 4.88 0.73 (0.39, 0.89) 9.33 PI 300 ± 74.0 282 ± 62.6 285 ± 53.2 0.70 (0.34, 0.88) 10.74 0.51 (0.07, 0.79) 12.65 AMPRF 1.81 ± 0.60 1.71 ±0.46 1.75 ± 0.60 0.85 (0.64, 0.94) 6.65 0.66 (0.28, 0.86) 12.61 AMPBZ 2.18 ± 0.67 2.10 ± 0.51 2.13 ± 0.67 0.86 (0.66, 0.95) 5.53 0.75 (0.45, 0.90) 10.27 AUCRF 134 ± 60.1 125 ± 48.8 117 ± 40 0.88 (0.70, 0.95) 10.63 0.50 (0.04, 0.79) 16.64 AUCBZ 231 ±83.3 219 ± 63.2 207 ± 55.8 0.91 (0.74, 0.97) 6.46 0.66 (0.27, 0.86) 11.97 1‐min AUC 114 ± 34.0 112 ± 30.9 111 ± 32.2 0.94 (0.83, 0.98) 4.83 0.77 (0.47, 0.91) 9.70 AUC index 3.15 ± 0.53 3.06 ± 0.54 3.04 ± 0.39 0.84 (0.62, 0.94) 4.82 0.33 (−0.18, 0.69) 9.35 ORC5 0.37 ± 0.10 0.36 ± 0.10 0.35 ± 0.10 0.89 (0.72, 0.96) 6.95 0.73 (0.4, 0.89) 9.52 ORC10 0.21 ± 0.05 0.20 ± 0.04 0.20 ± 0.06 0.83 (0.58, 0.93) 6.33 0.71 (0.38, 0.89) 8.39 ORC15 0.15 ± 0.04 0.14 ± 0.03 0.15 ± 0.04 0.85 (0.64, 0.94) 5.13 0.74 (0.43, 0.90) 8.65 ORC20 0.11 ± 0.03 0.11 ± 0.03 0.11 ± 0.04 0.87 (0.69, 0.95) 4.83 0.69 (0.34, 0.88) 10.70 ORCMF 0.12 ± 0.05 0.12 ± 0.04 0.12 ± 0.05 0.74 (0.41, 0.90) 15.27 0.22 (−0.31, 0.63) 22.90

Myocardial Flow Reserve by N13 Ammonia Positron Emission Tomography Predicts Post-Heart Transplant Outcomes

Cardiac allograft vasculopathy (CAV) is a pan-arterial disease, characterized by intimal thickening, fibrosis, and decreased coronary blood flow. It is common (50-65% 10 years post-HT) and is among the leading causes of death following heart transplantation (HT). Screening has traditionally evaluated the epicardial coronary arteries and microvascular dysfunction has been largely overlooked. Recent data suggests poor outcomes among HT patients with low myocardial flow reserve (MFR), a parameter capable of assessing microvascular function. We sought to identify the impact of MFR on death, retransplantation (ReTx), or cardiovascular (CV) hospitalization. This prospective study enrolled 181 (206 screened, 3 studies were technically limited, 22 had high rest flows) patients who underwent 13N ammonia PET with CT attenuation correction between 2016-2017. Patients were followed for clinical outcomes including rejection (cellular or antibody mediated rejection [AMR]), graft function, and CAV. The optimal MFR cut off was determined by a receiver operator characteristic curve. Among the cohort, MFR was highly predictive of the combined endpoint (HR 7.58, p<0.001). The ideal MFR cut point was 1.96 (AUC 0.76, 65.2% Sensitivity, 75.2 Specificity, 93.3 NPV). The group with a MFR<1.96 was more predominantly male, older (mean 5 years), further post-HT (mean 1.5 years), with more DM2, more CKD, fewer received ASA, had more prior cellular & AMR, and more had ≥ISHLT CAV 1. Groups had similar cardiac index, EF, and immunosuppression. Those with a MFR<1.96 had an 11% absolute increase in events at 2 years (Figure, HR 10.75, p=0.002). This was consistent for death/ReTx (HR 9.8, p=0.003) and CV hospitalization (HR 11.5, p=0.001). After adjusting for time post-transplant, AMR, and ISHLT CAV, a MFR<1.96 remained the greatest predictor (HR 6.84, p=0.0006). Decreased MFR following heart transplant is associated with an increased risk of death, ReTx, or CV hospitalization.

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

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

Long-Term Effects of Transcatheter Aortic Valve Implantation on Coronary Hemodynamics in Patients With Concomitant Coronary Artery Disease and Severe Aortic Stenosis.

BackgroundAs younger patients are being considered for transcatheter aortic valve implantation (TAVI), the assessment and treatment of concomitant coronary artery disease is taking on increased importance.Methods and ResultsThirteen contemporary lower‐risk patients with TAVI with severe aortic stenosis (AS) and moderate‐severe coronary lesions were included. Patients underwent assessment of coronary hemodynamics in the presence of severe AS (pre‐TAVI), in the absence of severe AS (immediately post‐TAVI), and at longer‐term follow‐up (6 months post‐TAVI). Fractional flow reserve decreased from 0.85 (0.76–0.88) pre‐TAVI to 0.79 (0.74–0.83) post‐TAVI, and then to 0.71 (0.65–0.77) at 6‐month follow‐up (P<0.001 for all comparisons). Conversely, instantaneous wave‐free ratio was not significantly different: 0.82 (0.80–0.90) pre‐TAVI, 0.83 (0.77–0.88) post‐TAVI, and 0.83 (0.73–0.89) at 6 months (P=0.735). These changes are explained by the underlying coronary flow. Hyperemic whole‐cycle coronary flow (fractional flow reserve flow) increased from 26.36 cm/s (23.82–31.82 cm/s) pre‐TAVI to 30.78 cm/s (29.70–34.68 cm/s) post‐TAVI (P=0.012), to 40.20 cm/s (32.14–50.00 cm/s) at 6‐month follow‐up (P<0.001 for both comparisons). Resting flow during the wave‐free period of diastole was not significantly different: 25.48 cm/s (21.12–33.65 cm/s) pre‐TAVI, 24.54 cm/s (20.74–27.88 cm/s) post‐TAVI, and 25.89 cm/s (22.57–28.96 cm/s) at 6 months (P=0.500).Conclusions TAVI acutely improves whole‐cycle hyperemic coronary flow, with ongoing sustained improvements at longer‐term follow‐up. This enhanced response to hyperemic stimuli appears to make fractional flow reserve assessment less suitable for patients with severe AS. Conversely, resting diastolic flow is not significantly influenced by the presence of severe AS. Resting indices of coronary stenosis severity, therefore, appear to be more appropriate for this patient population, although large‐scale prospective randomized trials will be required to determine the role of coronary physiology in patients with severe AS.

Relation of cardiac adipose tissue to coronary calcification and myocardial microvascular function in type 1 and type 2 diabetes

BackgroundCardiac adipose tissue may have local paracrine effects on epicardial arteries and the underlying myocardium, promoting calcification and affecting myocardial microcirculation. We explored whether the total amount of cardiac adipose tissue was associated with coronary artery calcium score (CAC) and myocardial flow reserve in persons with type 1 or type 2 diabetes and healthy controls.MethodsWe studied three groups: (1) 30 controls, (2) 60 persons with type 1 diabetes and (3) 60 persons with type 2 diabetes. The three groups were matched for sex and age. The three groups derived from retrospective analysis of two clinical studies. All underwent cardiac 82Rb positron emission tomography/computed tomography (PET/CT) scanning. Cardiac adipose tissue volume (the sum of epicardial and pericardial fat), CAC, and myocardial flow reserve (ratio of pharmacological stress flow and rest flow) were evaluated using semiautomatic software. We applied linear regression to assess the association between cardiac adipose tissue, CAC and myocardial flow reserve.ResultsMean (SD) cardiac adipose tissue volume was 99 (61) mL in the control group, 106 (78) mL in the type 1 diabetes group and 228 (97) mL in the type 2 diabetes group. Cardiac adipose tissue was positively associated with body mass index in all three groups (p ≤ 0.02). In the controls, cardiac adipose tissue was positively associated with CAC score (p = 0.008) and negatively associated with myocardial flow reserve (p = 0.005). However, cardiac adipose tissue was not associated with CAC or myocardial flow reserve in the groups including persons with type 1 or type 2 diabetes (p ≥ 0.50).ConclusionsIn contrast to what was found in healthy controls, we could not establish a relation between cardiac adipose tissue and coronary calcification or myocardial microvascular function in person with type 1 or type 2 diabetes. The role of cardiac adipose tissue in cardiovascular disease in diabetes remains unclear.

Calculation of railway tunnels ventilation

"As a result of aerodynamics calculation the total stream of air flow from piston effect of moving train and effect after movement has been determined ('effect after movement' - The residual movement of air due to the inertia of the moving air mass, when the train has already left the tunnel and the piston effect is no longer directly in effect. So residual motion adds some air stream to the main air flow) in the railway tunnel of the Marabda-Akhalkalaki. It has been determined that for the condition of those tunnels, approximately 2/3 of air flow arisen from piston effect moves in the same direction as the train moves, while the rest flows to the opposite direction into the gap the perimeters of tunnel and train. This causes air turbulence and represents component of the general aerodynamic resistance. Despite of that, all galleries of the mentioned rail highway can be aired with natural draught resulted from piston effect. For the better use of draught, caused by the piston effect ventilation gaps should be arranged in each camera and niche, on both sides of the tunnel. The area of wide section in each air hole should be 5.6 m2. This activity will decrease aerodynamic resistance caused by the airflow in the gap of the tunnel and will guarantee air supply in the tunnel using piston effect. Thermo-physical calculation of tunnels ventilation has been performed and the work project for ventilation has been prepared. The present article sets out the results of the longest tunnel calculation. The presented results may be adjusted to shorter tunnels as well, because corresponding parameters for their conditions are milder and thus, appropriate to the norms. According to the calculation, the heat produced by the moving train can be neutralized with air flow of 4.8 m3/s in winter and 8.4 m3/s in summer. These air flows make sure to satisfy requirements for the maximum temperature so the temperature of airflow coming from the tunnel shall not exceed 35 ° C. 0 for any season. "

P3359Myocardial flow reserve using 13N ammonia PET for detection of cardiac allograft vasculopathy in heart transplant patients

Abstract Purpose Risk stratification and early detection of cardiac allograft vasculopathy (CAV) are essential in heart transplantation patients. CAV is associated with poor outcome in the chronic phase after heart transplantation. CAV presents a diffuse vascular involvement and has been difficult to noninvasively diagnose by the lack of a sensitive method to detect developing vascular pathology in the allograft. The present study investigates the ability of 13N-ammonia PET for detection of CAV in heart transplant patients. Methods Data of adenosine-stress 13N-ammonia PET imaging for thirty-one patients (mean age, 39 years-old) after 11 + 7 years from transplant was analyzed. Five patients had undergone percutaneous coronary intervention (PCI), and the remaining 26 patients had no history of definite myocardial ischemia. Myocardial flow was generated from the time activity curve of left ventricle input and myocardial uptake using 3-compartment model and the first 2 minutes' dataset of list-mode acquisition. Global - myocardial flow reserve (MFR) was calculated by stress to rest flow ratio. Patient with global-MFR &lt;2.0 was defined as significant decrease. Summed difference score (SDS) was used as an estimate for the extent of ischemia, and the patient showing SDS &gt;2 was identified as those having significant ischemia. Results The mean Global-MFR of our subjects were 2.3 (1.2 to 3.9). MFR using 13N-ammonia PET significantly decreases in one third of heart transplant patients in chronic stage. Eleven patients with Global-MFR &lt;2.0 (35%) were observed, and eight of them had no history of clinical myocardial ischemia. The proportion of patients with a history of PCI is 18% in patients with Global-MFR &lt;2.0 (vs 5%, p=0.210). Moreover, there were eight patients with SDS &gt;2 (26%) including three patients having a history of PCI. The proportion of patients with a history of PCI tends to be high with SDS &gt;2 (38% vs 9%, p=0.056). Conclusion This modality using 13N ammonia PET is useful for easily detection of CAV before manifestation of symptomatic myocardial ischemia in heart transplant patients.