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Objectives: We aimed to investigate the correlation between an overall cerebral small vessel disease (CSVD) burden and outcomes after endovascular treatment (EVT) for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Methods: In a multicenter registry study, we enrolled patients with EVT for anterior-circulation LVO-stroke. In 3.0-T MR imaging, we assessed 4 CSVD imaging markers, lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular spaces, each assigned a score of 0 or 1 and summed up to an overall CSVD burden score of 0–4. We dichotomized the overall CSVD severity as none to mild (score 0–2) and moderate to severe (3–4). Primary outcome was 90-day functional dependence or death (modified Rankin Scale (mRS) 3–6). Secondary outcomes included increase in NIH Stroke Scale ≥ 4 within 24 h (early neurological deterioration (END)) and within 7 days, symptomatic intracranial hemorrhage, 90-day mRS 2–6, and 90-day mortality. Results: Among 311 patients (63.0% male; mean age 65.1 ± 12.7 years), 260 (83.6%) had none-to-mild and 51 (16.4%) had moderate-to-severe overall CSVD burden. Moderate-to-severe CSVD burden was not significantly associated with the primary outcome (47.1% versus 45.4%; p > 0.05 in univariate and multivariate logistic regression), or the secondary outcomes except for a higher risk of END (11.8% versus 3.1%; p < 0.05 in multivariate analyses). Sensitivity analyses with 0–1 versus 2–4 of the CSVD burden score, and the score as an ordinal variable, showed similar results. Conclusions: An overall moderate-to-severe CSVD burden was not associated with 90-day functional dependence or death, after EVT for anterior-circulation LVO. Trial registration: ChiCTR1900022154 Key Points: • Moderate-to-severe cerebral small vessel disease burden on MRI should not be an exclusion indicator in determining the eligibility of an acute ischemic stroke patient for endovascular treatment. [ABSTRACT FROM AUTHOR]

We aimed to investigate the roles of antegrade residual flow and leptomeningeal collateral flow in sustaining cerebral perfusion distal to an intracranial atherosclerotic stenosis (ICAS). Patients with apparently normal cerebral perfusion distal to a symptomatic middle cerebral artery (MCA)-M1 stenosis were enrolled. Computational fluid dynamics models were built based on CT angiography to obtain a translesional pressure ratio (PR) to gauge the residual antegrade flow. Leptomeningeal collaterals (LMCs) were scaled on CT angiography. Cerebral perfusion metrics were obtained in CT perfusion maps. Among 83 patients, linear regression analyses revealed that both translesional PR and LMC scale were independently associated with relative ipsilesional mean transit time (rMTT). Subgroup analyses showed that ipsilesional rMTT was significantly associated with translesional PR (p < 0.001) rather than LMC scale in those with a moderate (50–69%) MCA stenosis, which, however, was only significantly associated with LMC scale (p = 0.051) in those with a severe (70–99%) stenosis. Antegrade residual flow and leptomeningeal collateral flow have complementary effects in sustaining cerebral perfusion distal to an ICAS, while cerebral perfusion may rely more on the collateral circulation in those with a severe stenosis. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether hemodynamic features of symptomatic intracranial atherosclerotic stenosis (sICAS) might correlate with the risk of stroke relapse, using a computational fluid dynamics (CFD) model.Methods: In a cohort study, we recruited patients with acute ischemic stroke attributed to 50 to 99% ICAS confirmed by computed tomographic angiography (CTA). With CTA-based CFD models, translesional pressure ratio (PR = pressurepoststenotic /pressureprestenotic ) and translesional wall shear stress ratio (WSSR = WSSstenotic - throat /WSSprestenotic ) were obtained in each sICAS lesion. Translesional PR ≤ median was defined as low PR and WSSR ≥4th quartile as high WSSR. All patients received standard medical treatment. The primary outcome was recurrent ischemic stroke in the same territory (SIT) within 1 year.Results: Overall, 245 patients (median age = 61 years, 63.7% males) were analyzed. Median translesional PR was 0.94 (interquartile range [IQR] = 0.87-0.97); median translesional WSSR was 13.3 (IQR = 7.0-26.7). SIT occurred in 20 (8.2%) patients, mostly with multiple infarcts in the border zone and/or cortical regions. In multivariate Cox regression, low PR (adjusted hazard ratio [HR] = 3.16, p = 0.026) and high WSSR (adjusted HR = 3.05, p = 0.014) were independently associated with SIT. Patients with both low PR and high WSSR had significantly higher risk of SIT than those with normal PR and WSSR (risk = 17.5% vs 3.0%, adjusted HR = 7.52, p = 0.004).Interpretation: This work represents a step forward in utilizing computational flow simulation techniques in studying intracranial atherosclerotic disease. It reveals a hemodynamic pattern of sICAS that is more prone to stroke relapse, and supports hypoperfusion and artery-to-artery embolism as common mechanisms of ischemic stroke in such patients. Ann Neurol 2019;85:752-764. [ABSTRACT FROM AUTHOR]

Background: Intracranial arterial stenosis (ICAS) is a predominant cause of ischemic stroke in Asia. Changes in the signal intensities (SIs) across ICAS lesions on time-of-flight magnetic resonance angiography (TOF-MRA) have been indicated to partially reflect the hemodynamic significance of the lesions, which we aimed to verify by correlating it with cerebral perfusion features provided by CT perfusion (CTP) imaging. Methods: Ischemic stroke or transient ischemic attack patients with unilateral symptomatic stenosis ( ≥ 50%) of intracranial internal carotid artery or middle cerebral artery (MCA) were included in this study. Change of SIs across an ICAS lesion on TOF-MRA was calculated by the distal and proximal SI ratio (SIR). Cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) within the MCA territory of ipsilateral and contralateral hemispheres were evaluated on the CTP images at the basal ganglia level. Relative CBV, CBF and MTT were defined as ratios of the values obtained from ipsilateral and contralateral hemispheres. The relationships between SIR and CTP parameters were analyzed. Results: Fifty subjects (74% male, mean age 62) were recruited. Overall, the mean SIR was 0.77 ± 0.17. SIR of ICAS was significantly, linearly and negatively correlated with ipsilateral CBV (r = -0.335, p = 0.017), ipsilateral MTT (r = -0.301, p = 0.034), and ipsilateral/contralateral MTT ratio (r = -0.443, p = 0.001). Conclusions: Diminished SIs distal to ICAS on TOF-MRA might be associated with delayed ipsilateral cerebral perfusion. Changes of the SIs across ICAS lesions on TOFMRA may be a simple marker to reflect cerebral perfusion changes in patients with symptomatic ICAS. [ABSTRACT FROM AUTHOR]

Background: Pre-treatment collateral status may be associated with the rates of successful revascularization in acute ischemic stroke patients receiving endovascular treatment (EVT). We conducted a systematic review and meta-analysis to synthesize relevant evidence currently available. Methods: Relevant full-text articles published in English since January 1, 2000, reporting associations between collateral status and successful reperfusion and/or recanalization in acute ischemic stroke patients receiving EVT in cohort or case-control studies, or randomized clinical trials, were retrieved through search of PubMed. Study selection, data extraction and study quality assessment were carried out by 2 investigators. Risk ratios (RR) were pooled for good vs. poor collaterals for the outcomes of successful reperfusion and recanalization, based on random-effects models. Subgroup analyses were conducted to explore for potential factors that might interfere with the effects of pre-treatment collateral status on reperfusion by EVT. Results: In total, 27 studies (2,366 subjects) were included in qualitative analysis, among which 24 studies (2,239 subjects) were quantitatively analyzed. Overall, good pre-treatment collaterals significantly increased the rate of both successful reperfusion (RR 1.28, 95% CI 1.17-1.40; p < 0.001) and recanalization (RR 1.23, 95% CI 1.06-1.42; p = 0.006), as compared with poor collaterals. Subgroup analyses revealed that the effects of collateral status on successful reperfusion by EVT might be different between populations with different ethnicities. Conclusions: Good pre-treatment collaterals may enhance the rates of successful reperfusion and recanalization in EVT for acute ischemic stroke. This may partly explain the favorable effects of good pre-treatment collaterals on clinical outcomes of stroke patients receiving EVT. Thus, it would be valuable to assess the collateral status prior to EVT in acute ischemic stroke. But studies are needed to further verify if the positive effects of good collaterals on revascularization by EVT are restricted to certain subgroups of patients. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Patients with symptomatic intracranial atherosclerosis (ICAS) of ≥70% luminal stenosis are at high risk of stroke recurrence. We aimed to evaluate the relationships between hemodynamics of ICAS revealed by computational fluid dynamics (CFD) models and risk of stroke recurrence in this patient subset. Methods: Patients with a symptomatic ICAS lesion of 70–99% luminal stenosis were screened and enrolled in this study. CFD models were reconstructed based on baseline computed tomographic angiography (CTA) source images, to reveal hemodynamics of the qualifying symptomatic ICAS lesions. Change of pressures across a lesion was represented by the ratio of post- and pre-stenotic pressures. Change of shear strain rates (SSR) across a lesion was represented by the ratio of SSRs at the stenotic throat and proximal normal vessel segment, similar for the change of flow velocities. Patients were followed up for 1 year. Results: Overall, 32 patients (median age 65; 59.4% males) were recruited. The median pressure, SSR and velocity ratios for the ICAS lesions were 0.40 (−2.46–0.79), 4.5 (2.2–20.6), and 7.4 (5.2–12.5), respectively. SSR ratio (hazard ratio [HR] 1.027; 95% confidence interval [CI], 1.004–1.051; P = 0.023) and velocity ratio (HR 1.029; 95% CI, 1.002–1.056; P = 0.035) were significantly related to recurrent territorial ischemic stroke within 1 year by univariate Cox regression, respectively with the c-statistics of 0.776 (95% CI, 0.594–0.903; P = 0.014) and 0.776 (95% CI, 0.594–0.903; P = 0.002) in receiver operating characteristic analysis. Conclusions: Hemodynamics of ICAS on CFD models reconstructed from routinely obtained CTA images may predict subsequent stroke recurrence in patients with a symptomatic ICAS lesion of 70–99% luminal stenosis. [ABSTRACT FROM AUTHOR]

Background: Intracranial arterial stenosis (ICAS) is the predominant cause of ischemic stroke and transient ischemic attack in Asia. Change of signal intensities (SI) across an ICAS on magnetic resonance angiography (MRA) may reflect its hemodynamic severity. Methods: In-patients with a symptomatic single ICAS detected on 3D time-of-flight MRA were recruited from 2 hospitals. Baseline and 1-year follow-up data were collected. Signal intensity ratio (SIR) [ =  (mean post-stenotic SI -mean background SI)/(mean pre-stenotic SI - mean background SI)] was evaluated on baseline MRA to represent change of SIs across an ICAS. Acute infarct volume was measured on baseline diffusion-weighted images (DWI). Relationships between SIR and baseline characteristics as well as 1y outcomes were evaluated. Results: Thirty-six subjects (86.1% males, mean age 55.0) were recruited. Overall, mean SIR was 0.84±0.23. Mean SIRs were not significantly different between the 23 (63.9%) anatomically severe stenoses and the 13 (36.1%) anatomically moderate stenoses (0.80±0.23 versus 0.92±0.21, p = 0.126). SIR was significantly, linearly and negatively correlated to acute infarct volume on DWI (Spearman correlation coefficient −0.471, p = 0.011). Two patients (5.6%) had recurrent ischemic strokes at 1y, not related to SIR values. Conclusions: Change of signal intensities across an ICAS on MRA may reflect its hemodynamic and functional severity. Future studies are warranted to further verify the relationships between this index and prognosis of patients with symptomatic ICAS. [ABSTRACT FROM AUTHOR]

Aims: The relationship between heme oxygenase‐1 (HO‐1) and human ischemic stroke outcome remains unclear, which was investigated in this study. Methods: Acute ischemic stroke patients admitted within 24 h were enrolled. Serum HO‐1 levels at baseline were measured via ELISA. Poor 3‐month functional outcome was defined as modified Rankin Scale (mRS) score 3–6. Multivariable‐adjusted binary logistic regression and restricted cubic spline models were employed to examine association between serum HO‐1 and functional outcome. HO‐1's additive prognostic utility was assessed by net reclassification index (NRI) and integrated discrimination improvement (IDI). Results: Of 194 eligible patients, 79 (40.7%) developed poor functional outcomes at 3‐month follow‐up. The highest quartile of serum HO‐1 was independently associated with a lower risk of poor functional outcome (adjusted OR 0.13, 95% CI 0.04–0.45; p = 0.001) compared with the lowest HO‐1 category. The relationship between higher HO‐1 levels and reduced risk of poor functional outcome was linear and dose responsive (p = 0.002 for linearity). Incorporating HO‐1 into the analysis with conventional factors significantly improved reclassification for poor functional outcomes (NRI = 41.2%, p = 0.004; IDI = 5.0%, p = 0.004). Conclusions: Elevated serum HO‐1 levels at baseline were independently associated with improved 3‐month functional outcomes post‐ischemic stroke. Serum HO‐1 measurement may enhance outcome prediction beyond conventional clinical factors. [ABSTRACT FROM AUTHOR]

Background: Stroke caused by acute basilar artery occlusion (BAO) is devastating with high dependency and mortality. Recent trials have demonstrated the efficacy of endovascular treatment (EVT) for acute BAO, while pretreatment collaterals may be a valuable prognostic indicator for post-EVT outcomes. Aims: To systematically review and synthesize evidence on the associations between pretreatment collateral status and outcomes after EVT in acute BAO. Methods: We retrieved relevant full-text articles published in English since 1 January 2010, reporting associations between pretreatment collateral status and outcomes after EVT for BAO, by searching MEDLINE and Embase. The primary outcome was favorable or good 90-day functional outcome (modified Rankin Scale [mRS] 0–2 or 0–3); secondary outcomes included successful recanalization, symptomatic intracranial hemorrhage, final infarct volume, and 90-day mortality. Risk ratios (RRs) with 95% confidence intervals (CIs) for good versus poor collaterals on the outcomes were synthesized using random-effects models. Subgroup and sensitivity analyses were conducted for the primary outcome. Results: Overall, 29 primary studies (2995 participants) were included in qualitative review, among which 16 studies (1447 participants) were meta-analyzed. With different imaging modalities and methods to grade the collateral status, good collaterals were found in 33–85% of patients in the individual primary studies (I2 = 95.2%, p < 0.001), with a pooled proportion of 51% (95% CI: 40–62%) across all studies. Good pretreatment collaterals were associated with a doubled rate of favorable/good 90-day functional outcome (RR = 2.03, 95% CI: 1.63–2.51, p < 0.001), a higher rate of successful recanalization (RR = 1.23, 95% CI: 1.04–1.45, p = 0.015), and reduced 90-day mortality (RR = 0.59, 95% CI: 0.43–0.81, p = 0.001) after EVT for BAO. None of the primary studies reported the associations of good collaterals with the other secondary outcomes. Subgroup analyses revealed possibly more prominent protective effect of good pretreatment collaterals over the primary outcome, in studies with longer time windows in patient eligibility criteria for EVT (p = 0.028 for between-subgroup heterogeneity). Conclusions: In patients with BAO receiving EVT, good pretreatment collateral status was associated with a higher chance of favorable 90-day functional outcome, despite the various methods in grading the collateral circulation. Efforts are needed for more standardized collateral assessment in BAO, for more reliable and generalizable investigations of its clinical implications. [ABSTRACT FROM AUTHOR]

A letter to the editor related to a study concerning the hemodynamic role and importance of intracranial arterial stenosis (ICAS) in diagnosing the risk of stroke in patients with symptomatic ICAS is presented.

Background and Objective: Drug–drug interactions between direct oral anticoagulants (DOAC) and antiseizure medications via the cytochrome P450 (CYP) or the P-glycoprotein (P-gp) systems may lead to under-anticoagulation. The clinical relevance of these interactions is unclear. We aimed to elucidate the risk of thromboembolism with concurrent DOAC and CYP/P-gp modulating antiseizure medications. Methods: In this propensity score-weighted population-based retrospective cohort study, we used competing risk regression analyses to determine the risks of ischemic stroke, venous thromboembolism, and death in DOAC recipients taking CYP/P-gp-modulating antiseizure medications (phenytoin, valproate, levetiracetam, carbamazepine, or phenobarbital) versus those taking CYP/P-gp-neutral antiseizure medications (pregabalin, gabapentin, or clobazam). We also performed secondary analyses for the epilepsy and atrial fibrillation subgroups. Results: Among DOAC users, CYP/P-gp-modulating antiseizure medications were collectively associated with an increased risk of ischemic stroke (adjusted hazard ratio 1.28, 95% confidence interval 1.05–1.57, p = 0.017). In addition, phenytoin (adjusted hazard ratio 1.34, 95% confidence interval 1.07–1.68, p = 0.011) and valproate (adjusted hazard ratio 1.38, 95% confidence interval 1.10–1.74, p = 0.006) were associated with increased mortality. In the epilepsy subgroup, the risk of ischemic stroke and venous thromboembolism did not differ between CYP/P-gp-modulating and CYP/P-gp-neutral antiseizure medications. Conclusions: Although CYP/P-gp-modulating antiseizure medications were associated with an increased risk of ischemic stroke when paired with DOAC in the primary analysis, such a phenomenon was not found among patients with epilepsy who took phenytoin, valproate, or levetiracetam with DOAC. Therefore, these antiseizure medication options among patients with epilepsy with concurrent DOAC should not be restricted solely based on their potential drug–drug interactions. Yet, the increased mortality during concurrent use of DOAC with phenytoin or valproate might call for caution. [ABSTRACT FROM AUTHOR]

Objective: Success in clinical trials of intracranial atherosclerosis (ICAS) is related to accurate identification of high-risk patients. Noninvasive computational fluid dynamics (CFD) of stenotic lesions may enhance therapeutic decision-making. We determined whether physiologic parameters change downstream cerebral hemodynamics in patients with ICAS.Methods: Consecutive ICAS patients who underwent both CT angiography (CTA) and digital subtraction angiography were enrolled. CFD models were made using CTA source images. Inlet boundary conditions were defined using three ranges of systolic blood pressure (BP) (109.2, 158, and 225 mmHg) and hematocrit (27.3, 40.2, and 48.8). Ratios of pressure, shear strain rates (SSR), and flow velocity across the lesion were calculated using CFD simulations. A linear mixed model was used for the statistical analysis of repeated simulations.Results: Among the 56 patients, 32 had moderate stenosis (50-69%) and 24 had severe stenosis (70-99%). A linear mixed model revealed that the ratio of pressure was predicted by systolic BP and stenosis group interaction (P = .036). These pressure decreases were associated with systolic BP (P < .001) and stenosis group (P < .001), but not with hematocrit (P = .337). Post-hoc analysis revealed that pressure decreases were more profound in the severe stenosis than the moderate stenosis group when comparing high and low systolic BP (P = .0108). Ratios of SSR and velocity were only associated in the stenosis group.Conclusions: Our study showed that systolic BP along with the degree of stenosis was associated with pressure decreases across stenotic lesions. Physiologic conditions may superimpose further changes in post-stenotic or downstream blood flow. [ABSTRACT FROM AUTHOR]

Background: Depicting the time trends of ischemic stroke subtypes may inform healthcare resource allocation on etiology-based stroke prevention and treatment. Aim: To reveal the evolving ischemic stroke subtypes from 2004 to 2018. Methods: We determined the stroke etiologies of consecutive first-ever transient ischemic attack or ischemic stroke patients admitted to a regional hospital in Hong Kong from 2004 to 2018. We analyzed the age-standardized incidences and the two-year recurrence rate of major ischemic stroke subtypes. Results: Among 6940 patients admitted from 2004 to 2018, age-standardized incidence of ischemic stroke declined from 187.0 to 127.4 per 100,000 population (p < 0.001), driven by the decrease in large artery disease (43.0–9.67 per 100,000 population (p < 0.001)), and small vessel disease (71.9–45.7 per 100,000 population (p < 0.001)). Age-standardized incidence of cardioembolic stroke did not change significantly (p = 0.2). Proportion of cardioembolic stroke increased from 20.4% in 2004–2006 to 29.3% in 2016–2018 (p < 0.001). Two-year recurrence rate of intracranial atherothrombotic stroke reduced from 19.3% to 5.1% (p < 0.001) with increased prescriptions of statin (p < 0.001) and dual antiplatelet therapy (p < 0.001). In parallel with increased anticoagulation use across the study period (p < 0.001), the two-year recurrence of AF-related stroke reduced from 18.9% to 6% (p < 0.001). Conclusion: Etiology-based risk factor control might have led to the diminishing stroke incidences related to atherosclerosis. To tackle the surge of AF-related strokes, arrhythmia screening, anticoagulation usage, and mechanical thrombectomy service should be reinforced. Comparable preventive strategies might alleviate the enormous stroke burden in mainland China. [ABSTRACT FROM AUTHOR]

Background: Emerging studies suggest that early administration of dual antiplatelet therapy may be better than monotherapy for prevention of early recurrent stroke and cardiovascular outcomes in acute ischemic stroke and transient ischemic attack (TIA). We performed a meta-analysis of randomized, controlled trials evaluating dual versus mono antiplatelet therapy for acute noncardioembolic ischemic stroke or TIA.Methods and Results: We assessed randomized, controlled trials investigating dual versus mono antiplatelet therapy published up to November 2012 and the CHANCE trial (Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events), for efficacy and safety outcomes in adult patients with acute noncardioembolic ischemic stroke or TIA with treatment initiated within 3 days of ictus. In total, 14 studies of 9012 patients were included in the systematic review and meta-analysis. Dual antiplatelet therapy significantly reduced risk of stroke recurrence (risk ratio, 0.69; 95% confidence interval, 0.60-0.80; P<0.001) and the composite outcome of stroke, TIA, acute coronary syndrome, and all death (risk ratio, 0.71; 95% confidence interval, 0.63-0.81; P<0.001) when compared with monotherapy, and nonsignificantly increased risk of major bleeding (risk ratio, 1.35; 95% confidence interval, 0.70-2.59, P=0.37). Analyses restricted to the CHANCE Trial or the 7 double-blind randomized, controlled trials showed similar results.Conclusions: For patients with acute noncardioembolic ischemic stroke or TIA, dual therapy was more effective than monotherapy in reducing risks of early recurrent stroke. The results of the CHANCE study are consistent with previous studies done in other parts of the world. [ABSTRACT FROM AUTHOR]

Objective. Hematoma expansion is closely associated with adverse functional outcomes in patients with intracerebral hemorrhage (ICH). Prediction of hematoma expansion would therefore be of great clinical significance. We therefore attempted to predict hematoma expansion using a dual-modal machine learning (ML) strategy which combines information from non-contrast computed tomography (NCCT) images and multiple clinical variables. Approach. We retrospectively identified 140 ICH patients (57 with hematoma expansion) with 5616 NCCT images of hematoma (2635 with hematoma expansion) and 10 clinical variables. The dual-modal ML strategy consists of two steps. The first step is to derive a mono-modal predictor from a deep convolutional neural network using solely NCCT images. The second step is to achieve a dual-modal predictor by combining the mono-modal predictor with 10 clinical variables to predict hematoma growth using a multi-layer perception network. Main results. For the mono-modal predictor, the best performance was merely 69.5% in accuracy with solely the NCCT images, whereas the dual-modal predictor could boost the accuracy greatly to be 86.5% by combining clinical variables. Significance. To our knowledge, this is the best performance from using ML to predict hematoma expansion. It could be potentially useful as a screening tool for high-risk patients with ICH, though further clinical tests would be necessary to show its performance on a larger cohort of patients. [ABSTRACT FROM AUTHOR]

• Coronary microcirculatory dysfunction could be simulated using computational fluid dynamics. • MR variations in a branch with mild stenosis has limited hemodynamic effects on other branches. • Increased MR in a highly stenosed branch increases the blood flow and iFR of its cognate branches. The instantaneous wave-free ratio (iFR) has been proposed to estimate the hemodynamic severity of atherosclerotic stenosis in coronary arteries. The atherosclerotic stenosis in a proximal coronary artery could change its distal microcirculatory resistance (MR). However, there is a lack of investigation about the effect of MR variation on the blood flow and iFR of stenotic coronary arteries. We aim to investigate the changes of blood flow and iFR caused by distal MR variation. Four three-dimensional models of coronary arteries were reconstructed from the computed tomography images of two normal cases and two cases with 74.9% and 96.4% (in area) stenoses in a large branch of left anterior descending artery (LAD). Computational fluid dynamics simulation was performed on each model under 6 MR situations: hyperemia as the reference situation, resting when MR was multiplied by 8/3 in all outlet branches, h-one-1.5 and h-one-2 when MR was multiplied by 1.5 and 2.0 in one branch (the stenotic, or the corresponding branch in normal case) of LAD, h-branches-1.5 and h-branches-2 when MR was multiplied by 1.5 and 2.0 in the stenotic/corresponding and its cognate branches. Flow rate and iFR of each outlet branch were then calculated and compared between different MR situations to investigate the effect of MR variation on flow rate and iFR. In the 74.9% stenosed and normal cases, referring to the hyperemia situation, the increase of MR in any branch significantly decreased its flow rate and increased its iFR, with limited effect on the flow rate (<3%) and iFR (<0.01) of other branches. However, in the 96.4% stenosed case, the doubled MR in the stenosed branch (h-one-2) significantly increased the flow rate (>10%) and iFR (>0.05) of its cognate branches. The increase of MR in a normal or mildly stenosed branch of coronary artery decreases its blood flow and increases its iFR, with limited effect on other branches. Whereas, the increase of MR in a severely stenotic large branch could significantly increase the flow velocity and iFR of its cognate branches. [ABSTRACT FROM AUTHOR]