Coronary Hemodynamics Research Articles

RESPONSE: Coronary Anatomy, Hemodynamics, and Racism: The New Cardiology Training Curriculum?

RESPONSE: Coronary Anatomy, Hemodynamics, and Racism: The New Cardiology Training Curriculum?

Abstract 12505: Clinical Characteristics of Patients With Vasospastic Angina Subjected to the Spasm Provocation Test Involving the Unavoidable Use of Nitroglycerin

Introduction: Multivessel spasm (MVS) has a prognostic impact in patients with vasospastic angina (VSA). Thus, assessing for the presence of MVS in both left coronary artery and right coronary artery is preferable in the spasm provocation test (SPT). The use of nitroglycerin is necessary to avoid the complications related to SPT; however, this unavoidable use of NTG (U-NTG) may decrease the detection of MVS. Hypothesis: We investigated the frequency of U-NTG during SPT and clarified the clinical characteristics in VSA patients, with U-NTG during STP. Methods: Total 142 patients with positive SPT were evaluated. A positive SPT was defined as >90% constriction in coronary arteries, accompanied by the chest symptoms and/or ischemic ST-T changes. When a coronary spasm occurred, we usually waited for the spontaneous relief of the coronary spasm. However, if a prolonged coronary spasm or unstable hemodynamics occurred, NTG was administered to relieve the coronary spasm promptly (U-NTG). Even when U-NTG was administered in one coronary artery, an additional SPT was performed on another coronary artery. The patients were divided into two groups according to U-NTG: U-NTG(+) (n = 42) and U-NTG(-), (n = 100). The clinical characteristics and frequencies of MVS and complications (unstable hemodynamics) during the SPT were compared between the groups. Results: Except for smoking status, all other clinical characteristics status did not differ significantly between the groups. More current smokers were observed in the U-NTG(+) group (29%) compared with that in the U-NTG(-) group (12%, p = 0.03). The frequency of MVD did not vary significantly between the groups, with 64% in the U-NTG(+) and 52% in the U-NTG(-). No significant difference was found between the groups in the frequency of severe complications during SPT, with 5% in U-NTG(+) and 3% in U-NTG(-). In U-NTG(+), the positive induction of coronary spasm in another coronary artery was 40% (17/42). Conclusions: Our results show that U-NTG occurred in ~30% of VSA patients, especially in current smokers, and that it did not decrease the detection of MVS and prevented severe complications during SPT. Therefore, U-NTG is acceptable during SPT, after which, another test may be performed to assess the presence of MVS.

Abstract 10176: Absolute Perfusion Increase in Remote Myocardium Following Chronic Total Coronary Occlusion Percutaneous Coronary Intervention

Introduction: Successful revascularization of a chronic total coronary occlusion (CTO) impacts coronary physiology of the remote myocardial territory. This study evaluated the impact of CTO percutaneous coronary intervention (PCI) on absolute perfusion in remote myocardium. Methods: A total of 164 patients underwent serial [ 15 O]H 2 O positron emission tomography (PET) perfusion imaging at baseline and 3 months after successful CTO PCI to evaluate changes in hyperemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) in remote myocardium subtended by non-target collateral donor coronary arteries. Results: Absolute perfusion indices in the CTO and remote myocardium showed a positive linear correlation before (hMBF: r=0.75, p<0.01; CFR: r=0.77, p<0.01) and after (hMBF: r=0.87, p<0.01; CFR: r=0.81, p<0.01) CTO PCI. An increase in absolute myocardial perfusion (hMBF: 2.29±0.67 to 2.48±0.75 mL·min -1 ·g -1 , p<0.01; CFR: 2.48±0.76 to 2.74±0.85, p<0.01) was observed in the remote myocardial territory between baseline and follow-up. Improvements in remote myocardial perfusion were largest in patients with higher increases in hMBF (β 0.55, 95% CI: 0.46-0.64, p<0.01) and CFR (β 0.52, 95% CI: 0.43-0.61, p<0.01) in the CTO territory, independent of clinical, angiographic and procedural characteristics. Furthermore, lower baseline (hMBF: p<0.01; CFR: p<0.01) and higher post-PCI perfusion (hMBF: p<0.01; CFR: p<0.01) in both the remote and CTO territory were associated with larger perfusion increases in remote myocardium. Conclusions: Baseline and post-PCI perfusion indices in remote and CTO myocardium were positively correlated. An overall increase in remote myocardial perfusion was observed following CTO PCI and the absolute perfusion increase in the CTO territory was an independent predictor of remote myocardial perfusion improvement. Successful CTO PCI impacts coronary hemodynamics in the closely interlinked CTO and remote myocardium.

Moving shear stress towards the clinic: preclinical comparison of optical coherence tomography-based versus angiography-based time-averaged wall shear stress estimations

Abstract Introduction Identification of coronary atherosclerotic plaques at risk of causing future acute coronary syndromes remains a major unmet clinical challenge. The addition of vessel biomechanics to intracoronary imaging derived evaluation of plaque morphology, improves identification of plaques likely to develop high risk features. We and others have developed a framework for intracoronary imaging (optical coherence tomography [OCT]) based 3D reconstructions of coronary arteries for computational fluid dynamics (CFD) simulations of shear stress, which are considered the current gold standard approach for quantification of coronary arterial haemodynamics. However, these approaches are time consuming and computationally intensive, resulting in a barrier to clinical uptake. Purpose Determination of time averaged wall shear stress (TAWSS) based on 3D coronary geometries from non-invasive 3D Quantitative Coronary Angiography (3D-QCA) has recently been developed (Pie Medical Imaging, Netherlands), which enables results of shear stress simulations to be available within 30 minutes. We sought to compare TAWSS determined from 3D-QCA with gold standard OCT-based CFD simulations in both normal and stenotic arteries in minipigs. Methods 15 normal and 5 stenotic minipig coronary arteries were studied. Anatomically matched 3D arterial geometries were reconstructed from 3D-QCA and OCT using common centrelines. Boundary conditions for simulations included directly measured inlet blood velocities; parabolic inlet flow profiles, zero pressure outlet; no-slip arterial walls; blood density: 1.05 g/ml; blood dynamic viscosity: 0.035 g/cm.s. Blood was modelled as Newtonian. 3D-QCA TAWSS was obtained with a Kratos Multi-Physics CFD solver. OCT-based simulations were performed using Abaqus/CFD v6.14. TAWSS was calculated for 80 axially matched segments for both methods (1200 and 400 paired comparisons for normal and stenotic arteries, respectively). Data were analysed using Bland-Altman and Wilcoxon matched-pairs signed ranked tests. Results Computation times for 3D-QCA and OCT-based CFD were approximately 30 minutes and 2 hours respectively. Axial profiles of TAWSS were similar between the two methods and there was agreement in TAWSS magnitudes and narrow 95% limits of agreement (Figure 1 and Figure 2). Using co-registered TAWSS maps generated by each method, we find similar spatial regional distributions of TAWSS in both normal and stenotic arteries. Conclusions Our data suggest that 3D-QCA based TAWSS is feasible in both normal and stenotic arteries. Spatial TAWSS distributions between the two methods are similar with agreement in matched TAWSS comparisons, though there are some small systematic differences in the absolute values of TAWSS, due to different resultant arterial geometries. These encouraging data suggest that further clinical evaluation of rapid TAWSS from 3D-QCA is warranted, which may facilitate clinical adoption of TAWSS assessment. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Medical Research Council

Coronary haemodynamics associated with left ventricular hypertrophy in aortic stenosis and hypertension

Abstract Background Left ventricular hypertrophy (LVH) occurs in both aortic stenosis (AS) and hypertension (HT) due to an increase in afterload. However, in AS there is an increase in resting coronary flow (per gram of LV) while in HT it is reduced. Wave intensity analysis (WIA) is a well-established method of characterising and quantifying the energies that drive coronary flow. Energies propagating from the proximal vessel (aorta and systemic arteries) interact with energies travelling from the distal end (myocardial microcirculation). WIA allows the separation of these energies into the waves that drive cyclic changes in coronary flow. Purpose We aimed to compare coronary flow patterns in LVH secondary to AS with coronary flow patterns in LVH secondary to HT. Methods Thirty-one participants were recruited (mean age 63, 18 female), 10 with LVH and severe AS, 11 with LVH and HT, and 10 with no LVH and no AS. Participants underwent invasive pressure and Doppler velocity measurements in each of the left coronary arteries and echocardiography. We applied WIA. Results Mean resting coronary flow per gram of LV tissue (Fig. 1) was increased in participants with LVH secondary to AS (1.62±0.60 ml/min/g) and reduced in participants with LVH secondary to HT (0.49±0.27 ml/min/g), compared to participants with no LVH and no AS (1.47±0.73 ml/min/g). We observed marked differences between the magnitudes of the waves driving coronary flow in the three groups (Fig. 2). Forward and backward travelling waves are shown above and below the line respectively. Waves causing acceleration of coronary forward flow are shown as black and waves causing deceleration are shown in white. Wave 6, the backwards decompression wave (BDW), is particularly important for myocardial perfusion. The BDW corresponds to the diastolic 'suction' of blood down the coronary arteries during myocardial relaxation. The energy of the BDW was increased in LVH secondary to AS (31.1x103 W m–2 s–2) but was reduced in LVH secondary to HT (12.3x103 W m–2 s–2) (p<0.05), compared to participants with no LVH and no AS (14.3x103 W m–2 s–2). The energy of the BDW correlated with LV cavity pressure (r=0.84, p<0.001) and diastolic time (r=−0.62, p<0.001) only in LVH secondary to AS participants. In contrast, the BDW correlated with LV mass (r=−0.49, p=0.03) in participants with LVH secondary to HT and with no LVH and no AS, but not in participants with LVH secondary to AS. Conclusions In hypertension, LVH is associated with reduced mean coronary flow and reduced myocardial “suction” during diastole, presumably by the reduction in myocardial compliance associated with diastolic dysfunction. However, in AS the large pressure gradient between the LV cavity and the aorta results in a large contractile force which is generated in systole and then released in diastole. This large diastolic force overwhelms any local impairment caused by the hypertrophied myocardium and contributes to high resting coronary flow in AS. Funding Acknowledgement Type of funding sources: None.

Whole cycle non-hyperaemic pressure ratios have better stability than diastolic ratios after percutaneous coronary intervention due to changes in diastolic coronary haemodynamics

Abstract Background Post percutaneous intervention (PCI) fractional flow reserve (FFR) value of ≥0.90 is an accepted marker of procedural success, and similarly, a cut-off of ≥0.95 has recently been proposed for post-PCI instantaneous wave free ratio (iFR). However, the stability of non-hyperaemic pressure ratios (NHPRs) and microcirculatory resistance post-PCI, is not well characterised. as submaximal hyperaemia post-PCI may affect them. Purpose We performed this study to assess stability and reproducibility of NHPRs measured immediately post-PCI and repeated at 30 minutes post-PCI. Methods Seventy-seven patients undergoing pressure wire guided PCI (age 63.77±10.67 years, male 71%,) had haemodynamic assessment done immediately post-PCI and after a recovery period 30 minutes (Figure A, B). Manual offline analysis was performed to derive resting pressure ratios during whole cycle: average ratio of distal coronary pressure to proximal aortic pressure at rest (Pd/Pa) and resting full cycle ratio (RFR); and during diastolic phase: average diastolic pressure ratio (dPR) and mathematically calculated iFRmat, measured by average Pd/Pa during wave free period (WFP) (from 25% into diastole until 5 msec before the end of diastole). We also measured coronary flow velocity by thermo-dilution time (Tmn) and basal microvascular resistance (BMR = Pa × Tmn × [(Pd − Pw) / (Pa − Pw)] baseline) corrected for coronary wedge pressure (Pw). Test-retest statistics was performed between NHPRs values immediately post-PCI and at 30 minutes. Moreover, crossover of NHPRs across the cut-off value of 0.95 was analysed to assess clinical utility of these indices for procedural success. p value of <0.05 was deemed statistically significant. Results There were no differences in the baseline characteristics of the study patients. Sub-maximal hyperaemia was demonstrated by Tmn of 0.54 sec (0.32, 0.75) immediately post-PCI which settled by 30 minutes, Tmn of 0.67 sec (0.43, 0.91), p=0.01 (Figure C). The median BMR increased from 49.25 mmHg sec (32.74, 61.61) to 59.60 mmHg sec (39.24, 76.91) at 30 minutes, p=0.04 (Figure D). Despite this, there were no significant differences in the values of resting whole cycle ratios (Pd/Pa and RFR) as well as diastolic ratios (dPR and iFRmat), with whole cardiac cycle NHPRs having best stability post-PCI (Table). Furthermore, crossover above or below the cut-off value of 0.95 occurred in approximately 1 in 5 diastolic NHPRs measurements but was three-fold lower for whole cycle NHPRs. Conclusion NHPRs remain stable post-PCI, despite submaximal hyperaemia being detected and may legitimately be used immediately post-PCI to determine procedural success. However, the test-retest reproducibility and clinical utility of diastolic NHPRs (dPR and iFR) was inferior to whole cycle NHPRs (Pd/Pa and RFR). Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): NIHR

A 1D–3D Hybrid Model of Patient-Specific Coronary Hemodynamics

Coronary flow is affected by evolving events such as atherosclerotic plaque formation, rupture, and thrombosis, resulting in myocardial ischemia and infarction. Highly resolved 3D hemodynamic data at the stenosis is essential to model shear-sensitive thrombotic events in coronary artery disease. We developed a hybrid 1D-3D simulation framework to compute patient-specific coronary hemodynamics efficiently. A 1D model of the coronary flow is coupled to an image-based 3D model of the region of interest. This framework affords the advantages of reduced-order modeling, decreasing the global computational cost, without sacrificing the accuracy of the quantities of interest. We validated our 1D-3D model against full 3D coronary simulations in healthy and diseased conditions. Our results showed good agreement between the 3D and the 1D-3D models while reducing the computational cost by 40-fold compared to the 3D simulation. The 1D-3D model predicted left/right coronary flow distribution within 3% and provided an accurate estimation of fractional flow reserve and wall shear stress distribution at the stenosis comparable to the 3D simulation. Savings in computational cost may be significant in situations with changing geometry, such as growing thrombosis. Also, this approach would allow quantifying the time-dependent effect of thrombotic growth and occlusion on the global coronary circulation.

Computational modeling of blood component transport related to coronary artery thrombosis in Kawasaki disease.

Coronary artery thrombosis is the major risk associated with Kawasaki disease (KD). Long-term management of KD patients with persistent aneurysms requires a thrombotic risk assessment and clinical decisions regarding the administration of anticoagulation therapy. Computational fluid dynamics has demonstrated that abnormal KD coronary artery hemodynamics can be associated with thrombosis. However, the underlying mechanisms of clot formation are not yet fully understood. Here we present a new model incorporating data from patient-specific simulated velocity fields to track platelet activation and accumulation. We use a system of Reaction-Advection-Diffusion equations solved with a stabilized finite element method to describe the evolution of non-activated platelets and activated platelet concentrations [AP], local concentrations of adenosine diphosphate (ADP) and poly-phosphate (PolyP). The activation of platelets is modeled as a function of shear-rate exposure and local concentration of agonists. We compared the distribution of activated platelets in a healthy coronary case and six cases with coronary artery aneurysms caused by KD, including three with confirmed thrombosis. Results show spatial correlation between regions of higher concentration of activated platelets and the reported location of the clot, suggesting predictive capabilities of this model towards identifying regions at high risk for thrombosis. Also, the concentration levels of ADP and PolyP in cases with confirmed thrombosis are higher than the reported critical values associated with platelet aggregation (ADP) and activation of the intrinsic coagulation pathway (PolyP). These findings suggest the potential initiation of a coagulation pathway even in the absence of an extrinsic factor. Finally, computational simulations show that in regions of flow stagnation, biochemical activation, as a result of local agonist concentration, is dominant. Identifying the leading factors to a pro-coagulant environment in each case—mechanical or biochemical—could help define improved strategies for thrombosis prevention tailored for each patient.

Computed Tomography Coronary Angiography and Computational Fluid Dynamics Based Fractional Flow Reserve Before and After Percutaneous Coronary Intervention.

Invasive fractional flow reserve (FFR) is recommended to guide stent deployment. We previously introduced a non-invasive FFR calculation (FFRB) based on computed tomography coronary angiography (CTCA) with reduced-order computational fluid dynamics (CFD) and resistance boundary conditions. Current study aimed to assess the feasibility and accuracy of FFRB for predicting coronary hemodynamics before and after stenting, with invasive FFR as the reference. Twenty-five patients who had undergone CTCA were prospectively enrolled before invasive coronary angiography (ICA) and FFR-guided percutaneous coronary intervention (PCI) on 30 coronary vessels. Using reduced-order CFD with novel boundary conditions on three-dimensional (3D) patient-specific anatomic models reconstructed from CTCA, we calculated FFRB before and after virtual stenting. The latter simulated PCI by clipping stenotic segments from the 3D coronary models and replacing them with segments to mimic the deployed coronary stents. Pre- and post-virtual stenting FFRB were compared with FFR measured pre- and post-PCI by investigators blinded to FFRB results. Among 30 coronary lesions, pre-stenting FFRB (mean 0.69 ± 0.12) and FFR (mean 0.67 ± 0.13) exhibited good correlation (r = 0.86, p < 0.001) and agreement [mean difference 0.024, 95% limits of agreement (LoA): −0.11, 0.15]. Similarly, post-stenting FFRB (mean 0.84 ± 0.10) and FFR (mean 0.86 ± 0.08) exhibited fair correlation (r = 0.50, p < 0.001) and good agreement (mean difference 0.024, 95% LoA: −0.20, 0.16). The accuracy of FFRB for identifying post-stenting ischemic lesions (FFR ≤ 0.8) (residual ischemia) was 87% (sensitivity 80%, specificity 88%). Our novel FFRB, based on CTCA with reduced-order CFD and resistance boundary conditions, accurately predicts the hemodynamic effects of stenting which may serve as a tool in PCI planning.

The Use of Maximum Entropy to Enhance Wave Intensity Analysis: An Application to Coronary Arteries in Hypertrophic Obstructive Cardiomyopathy.

Background: Wave intensity analysis is useful for analyzing coronary hemodynamics. Much of its clinical application involves the identification of waves indicated by peaks in the wave intensity and relating their presence or absence to different cardiovascular events. However, the analysis of wave intensity peaks can be problematic because of the associated noise in the measurements. This study shows how wave intensity analysis can be enhanced by using a Maximum Entropy Method (MEM).Methods: We introduce a MEM to differentiate between “peaks” and “background” in wave intensity waveforms. We apply the method to the wave intensity waveforms measured in the left anterior descending coronary artery from 10 Hypertrophic Obstructive Cardiomyopathy (HOCM) and 11 Controls with normal cardiac function. We propose a naming convention for the significant waves and compare them across the cohorts.Results: Using a MEM enhances wave intensity analysis by identifying twice as many significant waves as previous studies. The results are robust when MEM is applied to the log transformed wave intensity data and when all of the measured data are used. Comparing waves across cohorts, we suggest that the absence of a forward expansion wave in HOCM can be taken as an indication of HOCM. Our results also indicate that the backward compression waves in HOCM are significantly larger than in Controls; unlike the forward compression waves where the wave energy in Controls is significantly higher than in HOCM. Comparing the smaller secondary waves revealed by MEM, we find some waves that are present in the majority of Controls and absent in almost all HOCM, and other waves that are present in some HOCM patients but entirely absent in Controls. This suggests some diagnostic utility in the clinical measurement of these waves, which can be a positive sign of HOCM or a subgroup with a particular pathology.Conclusion: The MEM enhances wave intensity analysis by identifying many more significant waves. The method is novel and can be applied to wave intensity analysis in all arteries. As an example, we show how it can be useful in the clinical study of hemodynamics in the coronary arteries in HOCM.

Comparing invasive hemodynamic responses in adenosine hyperemia versus physical exercise stress in chronic coronary syndromes

ObjectivesAdenosine hyperemia is an integral component of the physiological assessment of obstructive coronary artery disease in patients with chronic coronary syndrome (CCS). The aim of this study was to compare systemic, coronary and microcirculatory hemodynamics between intravenous (IV) adenosine hyperemia versus physical exercise stress in patients with CCS and coronary stenosis. MethodsTwenty-three patients (mean age, 60.6 ± 8.1 years) with CCS and single-vessel coronary stenosis underwent cardiac catheterization. Continuous trans-stenotic coronary pressure-flow measurements were performed during: i) IV adenosine hyperemia, and ii) physical exercise using a catheter-table-mounted supine ergometer. Systemic, coronary and microcirculatory hemodynamic responses were compared between IV adenosine and exercise stimuli. ResultsMean stenosis diameter was 74.6% ± 10.4. Median (interquartile range) FFR was 0.54 (0.44–0.72). At adenosine hyperemia versus exercise stress, mean aortic pressure (Pa, 91 ± 16 mmHg vs 99 ± 15 mmHg, p < 0.0001), distal coronary pressure (Pd, 58 ± 21 mmHg vs 69 ± 24 mmHg, p < 0.0001), trans-stenotic pressure ratio (Pd/Pa, 0.63 ± 0.18 vs 0.69 ± 0.19, p < 0.0001), microvascular resistance (MR, 2.9 ± 2.2 mmHg.cm−1.sec−1 vs 4.2 ± 1.7 mmHg.cm−1.sec−1, p = 0.001), heart rate (HR, 80 ± 15 bpm vs 85 ± 21 bpm, p = 0.02) and rate-pressure product (RPP, 7522 ± 2335 vs 9077 ± 3200, p = 0.0001) were all lower. Conversely, coronary flow velocity (APV, 23.7 ± 9.5 cm/s vs 18.5 ± 6.8 cm/s, p = 0.02) was higher. Additionally, temporal changes in Pa, Pd, Pd/Pa, MR, HR, RPP and APV during IV adenosine hyperemia versus exercise were all significantly different (p < 0.05 for all). ConclusionsIn patients with CCS and coronary stenosis, invasive hemodynamic responses differed markedly between IV adenosine hyperemia versus physical exercise stress. These differences were observed across systemic, coronary and microcirculatory hemodynamics.

Comparison of Swine and Human Computational Hemodynamics Models for the Study of Coronary Atherosclerosis

Coronary atherosclerosis is a leading cause of illness and death in Western World and its mechanisms are still non completely understood. Several animal models have been used to 1) study coronary atherosclerosis natural history and 2) propose predictive tools for this disease, that is asymptomatic for a long time, aiming for a direct translation of their findings to human coronary arteries. Among them, swine models are largely used due to the observed anatomical and pathophysiological similarities to humans. However, a direct comparison between swine and human models in terms of coronary hemodynamics, known to influence atherosclerotic onset/development, is still lacking. In this context, we performed a detailed comparative analysis between swine- and human-specific computational hemodynamic models of coronary arteries. The analysis involved several near-wall and intravascular flow descriptors, previously emerged as markers of coronary atherosclerosis initiation/progression, as well as anatomical features. To do that, non-culprit coronary arteries (18 right–RCA, 18 left anterior descending–LAD, 13 left circumflex–LCX coronary artery) from patients presenting with acute coronary syndrome were imaged by intravascular ultrasound and coronary computed tomography angiography. Similarly, the three main coronary arteries of ten adult mini-pigs were also imaged (10 RCA, 10 LAD, 10 LCX). The geometries of the imaged coronary arteries were reconstructed (49 human, 30 swine), and computational fluid dynamic simulations were performed by imposing individualized boundary conditions. Overall, no relevant differences in 1) wall shear stress-based quantities, 2) intravascular hemodynamics (in terms of helical flow features), and 3) anatomical features emerged between human- and swine-specific models. The findings of this study strongly support the use of swine-specific computational models to study and characterize the hemodynamic features linked to coronary atherosclerosis, sustaining the reliability of their translation to human vascular disease.

Variation of computed tomographic angiography-based fractional flow reserve after transcatheter aortic valve implantation.

We sought to identify the impact of transcatheter aortic valve implantation (TAVI) on changes of fractional flow reserve computed tomography (FFRCT) values and the associated clinical impact. A retrospective analysis was done with CT obtained pre-TAVI, prior to hospital discharge and at 1-year follow-up, which provided imaging sources for the calculation of FFRCT values based on an online platform. A total of 190 patients were enrolled. Patients with pre-procedural FFRCT value > 0.80 (i.e., negative) and ≤ 0.80 (i.e., positive) demonstrated a significantly opposite change in the value after TAVI (0.8798 vs. 0.8718, p < 0.001 and 0.7634 vs. 0.8222, p < 0.001, respectively). The history of coronary artery disease (CAD) was identified as an independent predictor for FFRCT changing from negative to positive after TAVI (odds ratio [OR] 2.927, 95% confidence interval [CI] 1.130-7.587, p = 0.027), with lesions more severely stenosed (OR 1.039, 95% CI 1.003-1.076, p = 0.034) and in left anterior descending coronary artery (LAD) (OR 3.939, 95% CI 1.060-14.637, p = 0.041) being prone to change. TAVI directly brings improvement in FFRCT values in patients with compromised coronary flow. Patients with a history of CAD, especially with lesions more severely stenosed and in LAD, were under risk of FFRCT changing from negative to positive after TAVI. •The effect of TAVI on coronary hemodynamics might be influenced by different ischemic severity and coronary territories reflected by FFRCT values. •As different FFRCT variations did not impact outcomes of TAVI patients, AS, but not coronary issues, may be the primary problem to affect, which needs further validation.

Optical Coherence Tomography-Based Patient-Specific Residual Multi-Thrombus Coronary Plaque Models With Fluid-Structure Interaction for Better Treatment Decisions: A Biomechanical Modeling Case Study.

Intracoronary thrombus from plaque erosion could cause fatal acute coronary syndrome (ACS). A conservative antithrombotic therapy has been proposed to treat ACS patients in lieu of stenting. It is speculated that the residual thrombus after aspiration thrombectomy would influence the prognosis of this treatment. However, biomechanical mechanisms affecting intracoronary thrombus remodeling and clinical outcome remain largely unknown. in vivo optical coherence tomography (OCT) data of a coronary plaque with two residual thrombi after antithrombotic therapy were acquired from an ACS patient with consent obtained. Three OCT-based fluid-structure interaction (FSI) models with different thrombus volumes, fluid-only, and structure-only models were constructed to simulate and compare the biomechanical interplay among blood flow, residual thrombus, and vessel wall mimicking different clinical situations. Our results showed that residual thrombus would decrease coronary volumetric flow rate by 9.3%, but elevate wall shear stress (WSS) by 29.4% and 75.5% at thrombi 1 and 2, respectively. WSS variations in a cardiac cycle from structure-only model were 12.1% and 13.5% higher at the two thrombus surfaces than those from FSI model. Intracoronary thrombi were subjected to compressive forces indicated by negative thrombus stress. Tandem intracoronary thrombus might influence coronary hemodynamics and solid mechanics differently. Computational modeling could be used to quantify biomechanical conditions under which patients could receive patient-specific treatment plan with optimized outcome after antithrombotic therapy. More patient studies with follow-up data are needed to continue the investigation and better understand mechanisms governing thrombus remodeling process.

A Spatiotemporal Analysis of a Fluid Structure Interaction Model of the Left Coronary Artery

Coronary artery disease is the second leading cause of death in the United States. Models of coronary arteries have been widely used to understand the hemodynamic drivers of the disease. Fluid-Structure Interaction (FSI) modeling of the coronary arteries provides information on both the forces that are created by the blood and the forces distributed into the artery wall. A better understanding of the artery health and markers of disease progression may be discernable by performing a spatiotemporal analysis of the coronary artery hemodynamics and solid mechanics. The goals of this investigation were: 1) to create a three-dimensional (3D) FSI model of the left anterior descending coronary artery and 2) to evaluate disease progression using multiple mechanical descriptors in both space and time domains using COMSOL Multiphysics. The 3D geometry reconstruction was based on a patient's computer tomography angiography (CTA) data. The fluid domain representing the blood volume and solid domain representing the artery wall were fully coupled. The artery wall was modeled using a 5-parameter hyperelastic Mooney-Rivlin material model. We assessed time averaged wall shear stress, wall shear stress gradient, and oscillatory shear index (OSI) along the fluid-structure interface. Artery wall strain (along the three principal directions) and Von-Mises stress were assessed within regions of the solid (i.e., the vascular wall). A virtual calculation of the Fractional Flow Reserve (vFFR), which is used for clinical diagnosis of cardiac ischemia, was performed. These analyses were collected from three different regions along the artery, proximal to, at, and distal to an area of narrowing in the artery throughout the cardiac cycle. Clear differences were observed between the regions. The distal region to the narrowing had variable OSI and high time averaged wall shear stress, but the lowest average Von-Mises stress. The vFFR was 0.96 which is comparable to the average FFR in the left anterior descending artery. This type of model reconstruction and analysis can be used to evaluate plaque vulnerabilities. It may also have clinical implications when assessing the patient's specific coronary artery mechanical environment that may lead to plaque development and instability.

Physiological Impact of Afterload Reduction on Cardiac Mechanics and Coronary Hemodynamics Following Isosorbide Dinitrate Administration in Ischemic Heart Disease

Understanding the cardiac-coronary interaction is fundamental to developing treatment strategies for ischemic heart disease. We sought to examine the impact of afterload reduction following isosorbide dinitrate (ISDN) administration on LV properties and coronary hemodynamics to further our understanding of the cardiac-coronary interaction. Novel methodology enabled real-time simultaneous acquisition and analysis of coronary and LV hemodynamics in vivo using coronary pressure-flow wires (used to derive coronary wave energies) and LV pressure-volume loop assessment. ISDN administration resulted in afterload reduction, reduced myocardial demand, and increased mechanical efficiency (all P<0.01). Correlations were demonstrated between the forward compression wave (FCW) and arterial elastance (r=0.6) following ISDN. In the presence of minimal microvascular resistance, coronary blood flow velocity exhibited an inverse relationship with LV elastance. In summary this study demonstrated a reduction in myocardial demand with ISDN, an inverse relationship between coronary blood flow velocity and LV contraction-relaxation and a direct correlation between FCW and arterial elastance.Graphical abstractThe pressure volume-loop and corresponding parameters b The pressure volume loop before (solid line) and after (broken line) Isosorbide dintrate

Liraglutide to Improve corONary haemodynamics during Exercise streSS (LIONESS): a double-blind randomised placebo-controlled crossover trial

BackgroundGlucagon-like peptide-1 receptor (GLP-1R) activation may improve myocardial performance in the context of ischaemia, independent of glycaemic control, in individuals with and without type 2 diabetes mellitus.MethodsThe LIONESS trial was a single-centre randomised double-blind placebo-controlled crossover study to determine whether prolonged GLP-1R activation could improve exercise haemodynamics in chronic stable angina patients. Eligibility criteria comprised angiographic evidence of obstructive coronary artery disease (CAD) and an abnormal baseline exercise tolerance test (ETT) demonstrating > 0.1 mV of planar or downsloping ST-segment depression (STD). Those randomised to active agent started with a 1-week run-in phase of 0.6 mg liraglutide daily, an established injectable GLP-1R agonist, followed by 1 week of 1.2 mg liraglutide, after which patients performed a week 2 ETT. Patients then self-administered 1.8 mg liraglutide for a week before completing a week 3 ETT. The placebo arm received visually and temporally matched daily saline injections. Participants then crossed over to a 3-week course of saline injections interspersed with a week 5 ETT and week 6 ETT and vice versa. Co-primary endpoints were rate pressure product (RPP) at 0.1 mV STD and magnitude of STD at peak exercise.ResultsTwenty-two patients (21 without diabetes) were randomised. There was no significant difference between saline versus liraglutide in the co-primary endpoints of RPP achieved at 0.1 mV STD (saline vs. liraglutide 1.2 mg p = 0.097; saline vs. liraglutide 1.8 mg p = 0.48) or the degree of STD at peak exercise (saline vs. liraglutide 1.2 mg p = 0.68; saline vs. liraglutide 1.8 mg p = 0.57). Liraglutide did not cause symptomatic hypoglycaemia, renal dysfunction, acute pancreatitis or provoke early withdrawal from the trial. Liraglutide significantly reduced weight (baseline 88.75 ± 16.5 kg vs. after liraglutide 87.78 ± 16.9 kg; p = 0.0008) and improved the lipid profile (mean total cholesterol: at baseline 3.97 ± 0.88 vs. after liraglutide 3.56 ± 0.71 mmol/L; p < 0.0001).ConclusionLiraglutide did not enhance exercise tolerance or haemodynamics compared with saline placebo during serial treadmill testing in patients with established obstructive CAD. It did, however, significantly reduce weight and improve the lipid profile.Trial Registration ClinicalTrials.gov Identifier NCT02315001. Retrospectively registered on 11th December 2014.

On the relevance of boundary conditions and viscosity models in blood flow simulations in patient-specific aorto-coronary bypass models.

Physiologically realistic results are the aim of every blood flow simulation. This is not different in aorto-coronary bypasses where the properties of the coronary circulation may significantly affect the relevance of the performed simulations. By considering three patient-specific bypass geometries, the present article focuses on two aspects of the coronary blood flow - its phasic flow pattern and its behaviour affected by blood rheology. For the phasic flow property, a multiscale modelling approach is chosen as a means to assess the ability of five different types of coronary boundary conditions (mean arterial pressure, Windkessel model and three lumped parameter models) to attain realistic coronary haemodynamics. From the analysed variants of boundary conditions, the best option in terms of physiological characteristics and its potential for use in patient-based simulations, is utilised to account for the effect of shear-dependent viscosity on the resulting haemodynamics and wall shear stress stimulation. Aside from the Newtonian model, the blood rheology is approximated by two non-Newtonian models in order to determine whether the choice of a viscosity model is important in simulations involving coronary circulation. A comprehensive analysis of obtained results demonstrated notable superiority of all lumped parameter models, especially in comparison to the constant outlet pressure, which regardless of bypass type gave overestimated and physiologically misleading results. In terms of rheology, it was noted that blood in undamaged coronary arteries behaves as a Newtonian fluid, whereas in vessels with atypical lumen geometry, such as that of anastomosis or stenosis, its shear-thinning behaviour should not be ignored.

Mechanisms of gradual pressure drop in angiographically normal left anterior descending and right coronary artery: Insights from wave intensity analysis

BackgroundThis study evaluated the mechanism of decline in coronary pressure from the proximal to the distal part of the coronary arteries in the left anterior descending (LAD) versus the right coronary artery (RCA) from the insight of coronary hemodynamics using wave intensity analysis (WIA). MethodsTwelve patients with angiographically normal LAD and RCA were prospectively enrolled. Distal coronary pressure, mean aortic pressure, and average peak velocity were measured at 4 different positions: 9, 6, 3, and 0 cm distal from each coronary ostium. ResultsThe distal-to-proximal coronary pressure ratio during maximum hyperemia gradually decreased in proportion to the distance from the ostium (0.92±0.03 and 0.98±0.03 at 9 cm distal to the LAD and RCA ostium). WIA showed the dominant forward-traveling compression wave gradually decreased and the backward-traveling suction wave gradually decreased in proportion to the decrease in coronary pressure through the length of the non-diseased LAD but not the RCA. ConclusionsThe pushing wave and suction wave intensities on WIA were diminished in proportion to the distance from the ostium of the LAD despite the wave intensity not changing across the length of the RCA, which may lead to gradual intracoronary pressure drop in the angiographically normal LAD.

A Hemodynamic Comparison of Myocardial Bridging and Coronary Atherosclerotic Stenosis: A Computational Model With Experimental Evaluation.

Myocardial bridging (MB) and coronary atherosclerotic stenosis can impair coronary blood flow and may cause myocardial ischemia or even heart attack. It remains unclear how MB and stenosis are similar or different regarding their impacts on coronary hemodynamics. The purpose of this study was to compare the hemodynamic effects of coronary stenosis and MB using experimental and computational fluid dynamics (CFD) approaches. For CFD modeling, three MB patients with different levels of lumen obstruction, mild, moderate, and severe were selected. Patient-specific left anterior descending (LAD) coronary artery models were reconstructed from biplane angiograms. For each MB patient, the virtually healthy and stenotic models were also simulated for comparison. In addition, an in vitro flow-loop was developed, and the pressure drop was measured for comparison. The CFD simulations results demonstrated that the difference between MB and stenosis increased with increasing MB/stenosis severity and flowrate. Experimental results showed that increasing the MB length (by 140%) only had significant impact on the pressure drop in the severe MB (39% increase at the exercise), but increasing the stenosis length dramatically increased the pressure drop in both moderate and severe stenoses at all flow rates (31% and 93% increase at the exercise, respectively). Both CFD and experimental results confirmed that the MB had a higher maximum and a lower mean pressure drop in comparison with the stenosis, regardless of the degree of lumen obstruction. A better understanding of MB and atherosclerotic stenosis may improve the therapeutic strategies in coronary disease patients and prevent acute coronary syndromes.