Coronary Resistance Research Articles

Absolute coronary flow and microvascular resistance reserve in patients with severe aortic stenosis

BackgroundDevelopment of left ventricle (LV) hypertrophy in aortic stenosis (AS) is accompanied by adaptive coronary flow regulation. We aimed to assess absolute coronary flow, microvascular resistance, coronary flow reverse (CFR)...

Haemodynamic characterisation of different endotypes in coronary artery vasospasm in reaction to acetylcholine.

Vasoreactivity testing with high-dose acetylcholine is considered vasospasm provocation and low-dose as endothelial function testing. To assess the changes in reaction to low- and high-dose acetylcholine in the endotypes of CAS as defined by the Coronary Vasomotor Disorders International Study Group (COVADIS) working group. Changes in coronary epicardial diameter, coronary blood flow (CBF) and vascular resistance were determined at low-dose acetylcholine. A total of 88 ANOCA patients were included in this analysis. In the negative group (n=14) incremental infusion of acetylcholine produced a progressive increase in CBF (p=0.008). In reaction to low-dose acetylcholine, the epicardial vasospasm group (n=30) is characterised by epicardial vasoconstriction that is significantly more severe compared to the microvascular vasospasm group (p=0.004)(n=23). The equivocal group (n=21) is characterised by an increase in CBF and reduction in vascular resistance that are both significantly different compared to the epicardial vasospasm group (p=0.036 and p=0.007, respectively). High-dose acetylcholine decreased epicardial diameter and CBF significantly in the epicardial vasospasm, microvascular vasospasm and in the equivocal group (all p<0.05. Vascular resistance increased significantly in the epicardial vasospasm group (p<0.001) and equivocal group (p=0.009). In reaction to low-dose acetylcholine the negative and equivocal endotype has haemodynamic changes that suggest intact endothelium. In reaction to high-dose acetylcholine the epicardial vasospasm, microvascular vasospasm and equivocal endotype have hemodynamic changes that suggest VSMC-hyperreactivity. These results suggest that the equivocal endotype is a positive test comparable to microvascular vasospasm in the presence of normal endothelial function.

Simulating Stenotic Conditions of the Coronary Artery in a Lumped Parameter Model of the Cardiovascular System.

Coronary flow control mechanisms maintain the average coronary blood flow (CBF) at 4% of the cardiac output (CO) in normal adults, with no prior diagnosis of coronary artery disease (CAD), under resting conditions. This paper explores a pulsatile sixth order lumped parameter (LP) model of the cardiovascular system (CVS) which utilizes the average CBF approximated from CO along with arterial blood pressure (ABP) waveform to estimate the coronary microvascular resistance using non-linear least square optimization technique. The CVS model includes a third order model of the coronary vascular bed and is shown to achieve phasic coronary flow. The coronary epicardial resistance is varied to emulate different degrees of stenosis and achieve realistic behavior of coronary microvascular resistance under these conditions.

The Complementary Value of Absolute Coronary Flow in the Assessment of Patients with Ischaemic Heart Disease

Fractional flow reserve (FFR) is the current gold standard invasive assessment of coronary artery disease (CAD). FFR reports coronary blood flow (CBF) as a fraction of a hypothetical and unknown normal value. Although used routinely to diagnose CAD and guide treatment, how accurately FFR predicts actual CBF changes remains unknown. In this study, we compared fractional CBF with absolute CBF (aCBF, in ml min−1), measured with a computational method during standard angiography and pressure wire assessment, on 203 diseased arteries (143 patients). We found a substantial correlation between the two measurements (r = 0.89 and Cohen’s kappa = 0.71). Concordance between fractional and absolute CBF reduction was high when FFR was >0.80 (91%) but reduced when FFR was ≤0.80 (81%), 0.70–0.80 (68%) and, particularly, 0.75–0.80 (62%). Discordance was associated with coronary microvascular resistance, vessel diameter and mass of myocardium subtended, all factors to which FFR is agnostic. Assessment of aCBF complements FFR and may be valuable to assess CBF, particularly in cases within the FFR ‘gray zone’.

Coronary Flow Evaluation in Heart Transplant Patients Compared to Healthy Controls Documents the Superiority of Coronary Flow Velocity Reserve Companion as Diagnostic and Prognostic Tool.

BackgroundDistinct contributions by functional or structural alterations of coronary microcirculation in heart transplantation (HT) and their prognostic role have not been fully elucidated. We aimed to identify the mechanisms of coronary microvascular dysfunction (CMD) in HT and their prognostic implications.Methods134 patients, surviving at least 5 years after HT, without evidence of angiographic vasculopathy or symptoms/signs of rejection were included. 50 healthy volunteers served as controls. All underwent the assessment of rest and hyperemic coronary diastolic peak flow velocity (DPVr and DPVh) and coronary flow velocity reserve (CFVR) and its inherent companion that is based on the adjusted quadratic mean: CCFVR = √{(DPVr)2 + (DPVh)2}. Additionally, basal and hyperemic coronary microvascular resistance (BMR and HMR) were estimated.ResultsBased on CFVR and DPVh, HT patients can be assigned to four endotypes: endotype 1, discordant with preserved CFVR (3.1 ± 0.4); endotype 2, concordant with preserved CFVR (3.4 ± 0.5); endotype 3, concordant with impaired CFVR (1.8 ± 0.3) and endotype 4, discordant with impaired CFVR (2.0 ± 0.2). Intriguingly, endotype 1 showed lower DPVr (p < 0.0001) and lower DPVh (p < 0.0001) than controls with lower CFVR (p < 0.0001) and lower CCFVR (p < 0.0001) than controls. Moreover, both BMR and HMR were higher in endotype 1 than in controls (p = 0.001 and p < 0.0001, respectively), suggesting structural microvascular remodeling. Conversely, endotype 2 was comparable to controls. A 13/32 (41%) patients in endotype 1 died in a follow up of 28 years and mortality rate was comparable to endotype 3 (14/31, 45%). However, CCFVR was < 80 cm/s in all 13 deaths of endotype 1 (characterized by preserved CFVR). At multivariable analysis, CMD, DPVh < 75 cm/s and CCFVR < 80 cm/s were independent predictors of mortality. The inclusion of CCFVR < 80 cm/s to models with clinical indicators of mortality better predicted survival, compared to only adding CMD or DPVh < 75 cm/s (p < 0.0001 and p = 0.03, respectively).ConclusionA normal CFVR could hide detection of microvasculopathy with high flow resistance and low flow velocities at rest. This microvasculopathy seems to be secondary to factors unrelated to HT (less rejections and more often diabetes). The combined use of CFVR and CCFVR provides more complete clinical and prognostic information on coronary microvasculopathy in HT.

Automation of intracoronary continuous thermodilution for absolute coronary flow and microvascular resistance measurements.

Microvascular resistance reserve (MRR) as derived from continuous intracoronary thermodilution specifically quantifies microvasculature function. As originally described, the technique necessitates reinstrumentation of the artery and manual reprogramming of the infusion pump when performing resting and hyperemic measurements. To simplify and to render this procedure operator-independent, we developed a fully automated method. The aim of the present study is to validate the automated procedure against the originally described one. For the automated procedure, an infusion pump was preprogrammed to allow paired resting-hyperemic thermodilution assessment without interruption. To validate the accuracy of this new approach, 20automated measurements were compared to those obtained in the same vessels with conventional paired resting-hyperemic thermodilution measurements (i.e., with a sensor pullback at each infusion rate and manual reprogramming of the infusion pump). A close correlation between the conventional and the automated measuring technique was found for resting flow (Qrest : r = 0.89, mean bias = 2.52; SD = 15.47), hyperemic flow (Qhyper : r = 0.88, mean bias = -2.65; SD = 27.96), resting microvascular resistance (Rμ-rest : r = 0.90, mean bias = 52.14; SD = 228.29), hyperemic microvascular resistance Rμ-hyper : r = 0.92, mean bias = 12.95; SD = 57.80), and MRR (MRR: r = 0.89, mean bias = 0.04, SD = 0.59). Procedural time was significantly shorter with the automated method (5'25″ ± 1'23″vs. 4'36″ ± 0'33″, p = 0.013). Continuous intracoronary thermodilution-derived measurements of absolute flow, absolute resistance, and MRR can be fully automated. This further shortens and simplifies the procedure when performing paired resting-hyperemic measurements.

CARD18: Successful Transplantation of Porcine Hearts after 24 hr of Cold Ischemia Following Resuscitation using Ex Vivo Normothermic Perfusion

Background: Cold storage of hearts is limited to 6 hr prior to transplant. Extending preservation time may impact transplant coordination and potentially increase the organ pool, as marginal organs can be evaluated during ex vivo preservation. This study employs normothermic ex vivo heart perfusion (NEVHP) for the resuscitation and evaluation of hearts after 24 hr of cold static storage followed by transplantation. Methods: Porcine hearts (n=8) were recovered using standard techniques with antegrade hypothermic cardioplegic arrest. A catheter was placed in the LV to assess function. Inflow and outflow catheters were placed into the aorta and PA, respectively. Hearts were then placed in cold static storage in CoStorSol™ solution at 5 degrees Celsius for 24 hr. Following cold storage, hearts were supported by NEVHP for 8 hr with in-parallel hemofiltration. Coronary perfusion was maintained at 1 mL/min/g cardiac tissue. After NEVHP, 3 hearts were transplanted into 3 recipient pigs and 5 hearts were electively terminated. Results: Using NEVHP, all hearts were successfully resuscitated, as defined by resumption of sinus rhythm and preserved LV function. During NEVHP, mean values for LV systolic pressure = 51.2 ± 4.1 mmHg; coronary resistance = 0.49 ± 0.05 mmHg/mL/min; oxygen consumption = 1.1 ± 0.1 mL/min; and serum lactate = 3.08 ± 0.2 mmol/L (Fig 1A-D). No statistical differences were identified at endpoint compared to hour one. Average weight gain was 4.4 ± 1.0 g. Following transplantation, time to full bypass wean after aortic cross clamp removal was 120 ± 14 min. Animals were supported off bypass for 90 min prior to elective euthanasia. Conclusions: Hearts that underwent cold static storage for 24 hr can be routinely resuscitated to viable function using NEVHP. In addition, ex vivo perfusion allows for assessment of organ function prior to transplantation. Successful transplantation of these hearts corroborates adequate resuscitation and confirms viability after NEVHP.

ADDITIVE DAMAGE IN THE CONTRACTILITY OF INTRAMURAL CORONARY ARTERIOLES IN A RAT MODEL OF ANDROPAUSAL HYPERTENSION

Objective: Hypertension accelerates vascular aging, and changes associated with vascular aging play a role in hypertension. Andropause also contributes to age – related vascular damage and increases cardiovascular risk. Our aim is to investigate the combined effect of hypertension and androgen deficiency on the contractility of intramural coronary resistance arteries. Design and method: Male Sprague-Dawley rats were distributed into 4 groups: control (Co, n = 10); orchidectomized (OCT, n = 13), angiotensin II infused (AII, n = 10) and AII infused plus orchidectomized (AII+OCT, n = 8). Early hypertension was established using osmotic minipumps containing angiotensin II (100 ng / min / kg), while testosterone deficiency achieved via orchidectomy. After 4 weeks, spontaneous, thromboxane- and bradykinin-induced tones of intramural coronary resistance arterioles were investigated by in vitro pressure microarteriography. Results: Inner radius was reduced in the AII+OCT group compared to all other groups. Spontaneous tone was significantly higher in AII and AII+OCT groups than in Co and OCT groups. U46619-induced vasoconstriction was significantly smaller in OCT and AII+OCT groups compared to Co and AII rats. Bradykinin-induced relaxation was also significantly reduced in orchidectomized rats (OCT and AII+OCT groups) to a greater extent than in Co and AII animals. Conclusions: Spontaneous vascular tone is increased in AII hypertension. As a result of orchidectomy, adaptation range of the blood vessels narrows both regarding vasoconstriction and vasodilation. Therefore, the reactivity of the coronary arterioles deteriorates due to testosterone deficiency. In case of parallel manifestation of hypertension and testosterone deficiency, these two effects add up, which may increase age-related cardiovascular risk significantly in men.

The quantitative relationship between coronary microcirculatory resistance and myocardial ischemia in patients with coronary artery disease

It was hypothesized that the microcirculatory resistance of resting state (Rm-res) might be a good predictor for ischemia. In this study, the quantitative relationship between Rm-res and myocardial ischemia in different stenosed degrees was explored and verified through retrospective analysis, and the diagnostic performance was evaluated. 136 patients were screened and divided into a training set (90 patients) and a validation set (46 patients). In the training set, Rm-res was calculated, and thresholds were determined by exploring the relationship between Rm-res and myocardial ischemia in different stenosed degrees. In the validation set, the diagnostic performance of the thresholds was verified. It was found that the 90 data mean difference (95%CI) of Rm-res between the ischemic group and the non-ischemic group was 63.03 (95 %CI: 25.72–100.34), p < 0.05. In the training set with stenosed degree 41–60%, 61–70%, 71–80%, and >81%, the average of Rm-res in the ischemic and non-ischemic groups were (80.79, 136.87), (96.41, 172.62), (128.99, 198.94) and (175.95, 310.79) mmHg/s/ml. The Rm-res thresholds were 87.18, 118.96, 142.35, and 177.39 mmHg/s/ml. In the validation set, the overall sensitivity, specificity, PPV, NPV, and accuracy were 73.3%, 77.4%, 61.1%, 85.7%, and 76.1%. In conclusion, Rm-res had a significant predictor on myocardial ischemia. As a smaller Rm-res represents greater myocardial mass perfusion, it is more likely that a stenosis will have a functional impact. Threshold analysis showed that Rm-res of different stenosed degrees was a quantitative predictor of myocardial ischemia, which could assist physicians with clinical treatment strategies.

Remote ischemic preconditioning promotes cardioprotection through a central nervous system dependent mechanism

Remote ischemic preconditioning (rIPC) is the phenomenon of brief periods of ischemia and reperfusion applied to a distant organ promote cardioprotection against a subsequent ischemia/reperfusion injury (I/R). Although a neurohumoral hypothesis has been proposed, the cardioprotective mechanisms of rIPC have not been fully elucidated. We investigated whether rIPC could induce cardioprotection in a pithed Wistar rat model hypothesizing that the absence of central nervous system (CNS) structures would prevent its cardioprotective effect. rIPC protocol consisting of 3 cycles of 4 minutes of ischemia and 4 minutes of reperfusion was applied to the left posterior extremity of male Wistar rats. I/R was induced surgically by left coronary descending artery ligation for 30 minutes followed by 2h of reperfusion. Isolated rat hearts were perfused in a Langendorff system to measure coronary vascular resistance (CVR). Finally, the infarct size was evaluated by Evans blue and triphenyltetrazolium staining. rIPC reduced the infarct size of the ischemic hearts; however, this effect was abolished in pithed rats. rIPC also prevented the rise of CVR of ischemic hearts while there was no difference compared to pithed rats. We concluded that rIPC reduces the infarct size of hearts during I/R preserving the coronary artery tone through a CNS‐dependent mechanism.

Exercise Training Attenuates Radiation‐Induced Impairments in Endothelium‐Dependent Vasodilation of Coronary Arterioles in Rats

BackgroundRadiation is an important and effective anti‐cancer therapy, but is associated with many side effects. Radiation exposure may cause damage to the heart and coronary vasculature. Exercise training is currently being investigated in cancer research as a treatment or adjuvant to anti‐cancer therapies, and has been shown to mitigate deleterious changes in coronary vascular function, such as with aging. We hypothesized that impairments in endothelium‐dependent vasodilation of coronary resistance arterioles that occur in response to radiation exposure would be mitigated with exercise training.Methods12 male Fischer 344 rats (3‐4 months old) were randomly assigned to one of four groups: control (CON; n=3), exercise (EX; n=3), control radiated (RAD; n=3), or exercise radiated (EX RAD; n=3). After increasing intensity over the first 3 weeks, EX and EX RAD animals ran on a motorized treadmill 5 days/week for 60 minutes/day, at an intensity of 15 m/min and 15° incline for the remainder of 12 weeks of training. After the conclusion of exercise training, all groups of animals were subjected 2 Gy whole body radiation by X‐Rad 350 x‐ray irradiator and euthanized within 8 hours. Hearts were harvested and left anterior descending (LAD) arteriole sections were isolated and fixed on glass pipets. Vessels were pressurized at 60 cm H2O. Once a minimum of 20% tone was developed, vessels were exposed to cumulative doses of bradykinin (10‐13‐10‐7 M), an endothelium‐dependent vasodilator, and vessel diameter was recorded at each dose.ResultsNo differences were detected for CON vs. EX or CON vs. EX RAD. Vasodilation for RAD was significantly reduced vs. CON (p = 0.007). EX RAD was significantly increased vs. RAD (p = 0.025).ConclusionsThere were no differences between CON and EX; however, vasodilation was impaired for radiated animals, suggesting even one dose of 2 Gy radiation can cause significant impairment in endothelium‐dependent vasodilation of coronary arterioles. Exercise training attenuated this impairment and restored endothelium‐dependent vasodilation to levels not different from control animals. These findings are significant, given that exercise training may be used as a simple and safe method to preserve coronary arteriole function in patients receiving radiation therapy.

Substrate Stiffness Modulates Normal and Diabetic Coronary Smooth Muscle Cell Stiffness

We have previously reported that coronary resistance microvessels (CRMs) from 16‐week‐old type 2 diabetic (db/db) mice were less stiff compared to normal heterozygous Db/db controls, a finding that was driven by less stiff coronary vascular smooth muscle cells (VSMCs). Because the surrounding extracellular matrix (ECM) substrates in vivo may impact cellular properties such as elastic modulus (a measure of stiffness), the aim of this study was to test the hypothesis that modulating substrate stiffness correspondingly modulates the elastic modulus of normal and diabetic coronary VSMCs in vitro. In this study, we plated low‐passage coronary VSMCs isolated from Db/db and db/db mice onto 60 mm polyacrylamide dishes (Matrigen) that were of varying stiffnesses – 4 kPa, 25 kPa, and 50 kPa (n=4 per group). Cells were serum starved for 24 hours, and then cell stiffness was measured by atomic force microscopy (AFM). We observed a stepwise increase in cellular elastic modulus with each increase in polyacrylamide substrate stiffness in both the normal and diabetic coronary VSMCs (Db/db 4 kPa = 3.39±0.48 kPa, Db/db 25 kPa = 5.46±0.78 kPa, Db/db 50 kPa = 7.13±0.29 kPa; db/db 4 kPa = 2.49±0.23, db/db 25 kPa = 5.00±0.52 kPa, db/db 50 kPa = 5.58±0.16 kPa, p&lt;0.0001). Similar to what we have previously reported on cells grown on plastic, diabetic coronary VSMCs were consistently less stiff compared to normal at each substrate stiffness. We did not observe statistically significant differences in cellular filamentous (F) actin, globular (G) actin, or the F/G actin ratio on the varying polyacrylamide substrate stiffness for neither Db/db nor db/db coronary VSMCs. However, there was a preliminary trend for lower F actin (Db/db: 1141.00 ± 472.20 AU vs. db/db: 422.50 ± 240.30 AU at 4 kPa, p=0.24, n=2 per group) and F/G actin ratio (Db/db: 4.01 ± 0.92 AU vs. db/db: 2.55 ± 0.35 AU at 4 kPa, p=0.21, n=2 per group) in the db/db VSMCs, corroborating our past data demonstrating that db/db coronary VSMCs are less stiff compared to normal Db/db coronary VSMCs. Overall, these data show that substrate stiffness correspondingly modulates normal and diabetic coronary VSMC stiffness.

Microcirculatory Function in Nonhypertrophic and Hypertrophic Myocardium in Patients With Aortic Valve Stenosis.

BackgroundLeft ventricular hypertrophy (LVH) has often been supposed to be associated with abnormal myocardial blood flow and resistance. The aim of this study was to evaluate and quantify the physiological and pathological changes in myocardial blood flow and microcirculatory resistance in patients with and without LVH attributable to severe aortic stenosis.Methods and ResultsAbsolute coronary blood flow and microvascular resistance were measured using a novel technique with continuous thermodilution and infusion of saline. In addition, myocardial mass was assessed with cardiac magnetic resonance imaging. Fifty‐three patients with aortic valve stenosis were enrolled in the study. In 32 patients with LVH, hyperemic blood flow per gram of tissue was significantly decreased compared with 21 patients without LVH (1.26±0.48 versus 1.66±0.65 mL·min−1·g−1; P=0.018), whereas minimal resistance indexed for left ventricular mass was significantly increased in patients with LVH (63 [47–82] versus 43 [35–63] Wood Units·kg; P=0.014).ConclusionsPatients with LVH attributable to severe aortic stenosis had lower hyperemic blood flow per gram of myocardium and higher minimal myocardial resistance compared with patients without LVH.

Comparison of fluid dynamics changes due to physical activity in 3D printed patient specific coronary phantoms with the Windkessel equivalent model of coronary flow

Background3D printing (3DP) used to replicate the geometry of normal and abnormal vascular pathologies has been demonstrated in many publications; however, reproduction of hemodynamic changes due to physical activities, such as rest versus moderate exercise, need to be investigated. We developed a new design for patient specific coronary phantoms, which allow adjustable physiological variables such as coronary distal resistance and coronary compliance in patients with coronary artery disease. The new design was tested in precise benchtop experiments and compared with a theoretical Windkessel electrical circuit equivalent, that models coronary flow and pressure using arterial resistance and compliance.MethodsFive phantoms from patients who underwent clinically indicated elective invasive coronary angiography were built from CCTA scans using multi-material 3D printing. Each phantom was used in a controlled flow system where patient specific flow conditions were simulated by a programmable cardiac pump. To simulate the arteriole and capillary beds flow resistance and the compliance for various physical activities, we designed a three-chamber outlet system which controls the outflow dynamics of each coronary tree. Benchtop pressure measurements were recorded using sensors embedded in each of the main coronary arteries. Using the Windkessel model, patient specific flow equivalent electrical circuit models were designed for each coronary tree branch, and flow in each artery was determined for known inflow conditions. Local flow resistances were calculated through Poiseuille’s Law derived from the radii and lengths of the coronary arteries using CT angiography based multi-planar reconstructions. The coronary stenosis flow rates from the benchtop and the electrical models were compared to the localized flow rates calculated from invasive pressure measurements recorded in the angio-suites.ResultsThe average Pearson correlations of the localized flow rates at the location of the stenosis between each of the models (Benchtop/Electrical, Benchtop/Angio, Electrical/Angio) are 0.970, 0.981, and 0.958 respectively.Conclusions3D printed coronary phantoms can be used to replicate the human arterial anatomy as well as blood flow conditions. It displays high levels of correlation when compared to hemodynamics calculated in electrically-equivalent coronary Windkessel models as well as invasive angio-suite pressure measurements.

Control of coronary vascular resistance by eicosanoids via a novel GPCR.

Arachidonic acid metabolites epoxyeicosatrienoates (EETs) and hydroxyeicosatetraenoates (HETEs) are important regulators of myocardial blood flow and coronary vascular resistance (CVR), but their mechanisms of action are not fully understood. We applied a chemoproteomics strategy using a clickable photoaffinity probe to identify G protein-coupled receptor 39 (GPR39) as a microvascular smooth muscle cell (mVSMC) receptor selective for two endogenous eicosanoids, 15-HETE and 14,15-EET, which act on the receptor to oppose each other's activity. The former increases mVSMC intracellular calcium via GPR39 and augments coronary microvascular resistance, and the latter inhibits these actions. Furthermore, we find that the efficacy of both ligands is potentiated by zinc acting as an allosteric modulator. Measurements of coronary perfusion pressure (CPP) in GPR39-null hearts using the Langendorff preparation indicate the receptor senses these eicosanoids to regulate microvascular tone. These results implicate GPR39 as an eicosanoid receptor and key regulator of myocardial tissue perfusion. Our findings will have a major impact on understanding the roles of eicosanoids in cardiovascular physiology and disease and provide an opportunity for the development of novel GPR39-targeting therapies for cardiovascular disease.

Is it all about age? Clinical characteristics of kawasaki disease in the extremely young: PeRA research group experience

ABSTRACT Objectives In the evaluation of children with Kawasaki disease (KD), the age of onset is important and complications may occur if the distinctive features are not assessed accordingly. The objective of the study is to define the clinical and laboratory presentations and treatment outcomes of KD in infants ≤6 months of age compared to those >6 months multicentrically. Methods This retrospective study reviewed the medical records of the patients diagnosed with KD and followed up between January 2009 and January 2019. Results A total of 204 KD patients were enrolled and grouped according to age as Group I (≤6 months, n = 31) and Group II (>6 months, n = 173). Except for cervical adenopathy (19.3% vs. 47.4%, p = 0.03), the major clinical manifestations of KD were similar between groups I and II. However, the frequency of incomplete and atypical KD was higher in Group I (38.7% vs. 24.8%, p = 0.04, 38.7% vs. 8.1% p < 0.001, respectively). Clinical features such as vomiting/diarrhea (19.3% vs. 1.1% p < 0.001), aseptic meningitis (19.3% vs. 2.3%, p = 0.001) were more common in Group I. Percentage of neutrophils (45.5 vs. 36, p = 0.004) and hemoglobin levels (8 vs. 10.5 gr/dL, p = 0.02) were statistically lower and platelet count (737,000 vs 400,000/mm3, p = 0.004) was statistically higher in group I. Coronary artery lesions (CALs) were more common in Group I (48% vs. 20%, p < 0.001). Harada and Kobayashi scores appear to be effective in predicting coronary artery lesions (CALs) and IVIG resistance in the entire cohort. There was no diagnostic delay in group I (5.5 vs 6.5 days, p = 0.88). Conclusions Since clinical presentations and laboratory features of KD may vary with age, and the frequency of atypical and incomplete presentations is high, awareness of KD in young children should be raised among pediatricians.

Refining Our Understanding of the Flow Through Coronary Artery Branches; Revisiting Murray's Law in Human Epicardial Coronary Arteries.

Background: Quantification of coronary blood flow is used to evaluate coronary artery disease, but our understanding of flow through branched systems is poor. Murray’s law defines coronary morphometric scaling, the relationship between flow (Q) and vessel diameter (D) and is the basis for minimum lumen area targets when intervening on bifurcation lesions. Murray’s original law (Q α DP) dictates that the exponent (P) is 3.0, whilst constant blood velocity throughout the system would suggest an exponent of 2.0. In human coronary arteries, the value of Murray’s exponent remains unknown. Aim: To establish the exponent in Murray’s power law relationship that best reproduces coronary blood flows (Q) and microvascular resistances (Rmicro) in a bifurcating coronary tree. Methods and Results: We screened 48 cases, and were able to evaluate inlet Q and Rmicro in 27 branched coronary arteries, taken from 20 patients, using a novel computational fluid dynamics (CFD) model which reconstructs 3D coronary anatomy from angiography and uses pressure-wire measurements to compute Q and Rmicro distribution in the main- and side-branches. Outputs were validated against invasive measurements using a Rayflow™ catheter. A Murray’s power law exponent of 2.15 produced the strongest correlation and closest agreement with inlet Q (zero bias, r = 0.47, p = 0.006) and an exponent of 2.38 produced the strongest correlation and closest agreement with Rmicro (zero bias, r = 0.66, p = 0.0001). Conclusions: The optimal power law exponents for Q and Rmicro were not 3.0, as dictated by Murray’s Law, but 2.15 and 2.38 respectively. These data will be useful in assessing patient-specific coronary physiology and tailoring revascularisation decisions.

Lactic Acid and Metabolic Analysis of Human Donor Hearts Preserved with Organ Care System

<h3>Purpose</h3> Primary graft dysfunction (PGD) is the most common cause of early death in patients of heart transplantation (HTx) and the requirement of ECMO is one of the definitive criteria of PGD. The Organ Care System (OCS) offers ex-vivo donor heart perfusion and currently, the decision to use the OCS preserved donor heart for HTx depends upon the lactate trend and the ventricular contractility. We performed a metabolic analysis of the OCS perfusate samples to predict donor hearts that may develop PGD following HTx. <h3>Methods</h3> Between February 2013 and September 2019, 204 donor hearts procured from the donation after brain death was assessed using OCS. 53 hearts were declined for HTx based on lactate trend and ventricular contractility (No Tx); whereas in the remaining 152 hearts that were transplanted, 42 recipients required ECMO following HTx (Tx with ECMO) while 109 recipients did not require ECMO (Tx without ECMO). <h3>Results</h3> The proportion of unfavourable lactate trend and high ‘end lactate' was significantly higher in the hearts declined for the HTx (no Tx group); however, there was no difference between ‘Tx with ECMO' and ‘Tx without ECMO' groups. The rate of fall of lactate was higher in the ‘Tx without ECMO' compared to the ‘Tx with ECMO'; however, did not reach statistical significance. Coronary blood flow was significantly low in the ‘No Tx' group compared to the other two groups. O2 content, O2 delivery and O2 return were significantly low in the No Tx group and these markers were higher in ‘Tx without ECMO' compared to ‘Tx with ECMO', although not statistically significant. The diastolic pressure and the coronary vascular resistance fell after 30 minutes of OCS perfusion in the donor hearts that did not suffer PGD whereas it remained high in the donor hearts that suffered PGD. <h3>Conclusion</h3> The rate of fall of arterial lactate offered more valuable information compared to the overall lactate trend and end lactate in the prediction of PGD after HTx. Hearts declined for the HTx based on the unfavourable lactate trend, high-end lactate and suboptimal ventricular contractility are justified by the metabolic analysis that showed significantly low CaO2, DO2 and Oxygen return in the declined hearts. Hearts procured from donors after brain death and preserved with OCS that show consistently high coronary vascular resistance may develop PGD requiring ECMO.

Prognostic value of microvascular resistance and its association to fractional flow reserve: a DEFINE-FLOW substudy

ObjectiveThis study aimed to evaluate the prognostic value of hyperemic microvascular resistance (HMR) and its relationship with hyperemic stenosis resistance (HSR) index and fractional flow reserve (FFR) in stable coronary...

PET Scan for CAV Screening in Heart Transplant Patients: A Real World Experience

<h3>Purpose</h3> Cardiac allograft vasculopathy (CAV) is a major cause of late morbidity and mortality after heart transplantation (HT). Positron emission tomography (PET) has emerged as a non-invasive screening modality, associated with invasive hemodynamic flow indices and outcomes in several small-scale studies. Our aim was to assess the real-world performance of 13N-Ammonia PET scan (PET) for the development of CAV. <h3>Methods</h3> Single center retrospective analysis of all HT patients who had an angiogram within one year before and after PET scan for CAV screening. CAV was defined as International Society of Heart and Lung Transplantation CAV_1-3. PET indices indicative of CAV were defined as any of: myocardial flow reserve (MFR) < 2.9, stress blood flow (SBF) < 2.3, or coronary vascular resistance (CVR) > 55. <h3>Results</h3> A total of 112 patients met study criteria, 13 were excluded for having CAV on pre-PET angiogram. Of the remaining 99 patients, Mean age was 52±14, 67 (68%) were males, 28 (28%) had ischemic cardiomyopathy, 35 (35%) had diabetes and 26 (26%) were hypertensive. PET was abnormal in 53 pts (54%). Repeat LHC demonstrated new CAV in 9 of these, all of whom had non-obstructive coronary artery disease (NCAD) on LHC. Overall PET had a 100% sensitivity and 51% specificity for identifying CAV. Two or more abnormal PET parameters showed 78% specificity (67% sensitivity) for the prediction of CAV. <h3>Conclusion</h3> Implementing a strategy of 13N-Ammonia PET scan performed a year after a negative LHC for CAV screening, resulted in excellent sensitivity but low specificity. Epicardial CAV was strongly associated with microvascular dysfunction evident by increased CVR and NCAD. Optimal PET thresholds for CAV screening need further refinement.