Impaired Myocardial Blood Flow Research Articles

Fully automated quantitative stress perfusion cardiac MRI to assess myocardial perfusion in adult patients with convalescent Kawasaki disease and coronary aneurysms: an age and sex-matched analysis

Abstract Introduction Coronary aneurysms are a well-documented complication of childhood Kawasaki disease. They may persist into adulthood predisposing to impaired myocardial blood flow, symptoms, and adverse cardiovascular events. Preliminary reports suggest that Kawasaki disease may also be associated with coronary microvascular dysfunction. The effect of coronary involvement from Kawasaki disease on myocardial perfusion in convalescent asymptomatic adults has not been studied using fully automated inline quantitative perfusion MRI (CMR). Purpose To assess the effect of coronary artery abnormalities on quantitative myocardial perfusion in adult patients with convalescent Kawasaki disease compared to an age and sex-matched control cohort. Methods Retrospective single centre cohort analysis of adult patients with convalescent Kawasaki disease who have undergone fully automated inline quantitative myocardial stress perfusion CMR. All patients had coronary involvement during their acute childhood illness. An age and sex-matched group (n=14) with normal CMRs was selected for comparison. Rest MBF was corrected for heart rate by dividing by the scan heart rate and multiplying by the mean resting heart rate among all subjects. A per-vessel analysis was performed using a linear mixed effects model with pairwise comparisons to assess the effect of coronary abnormalities (normal, aneurysmal with or without thrombosis, revascularised) on myocardial perfusion reserve (MPR). Results 28 patients were included (14 Kawasaki; 14 controls). All patients in the Kawasaki cohort had assessment of coronary anatomy either by CT (93%) or invasive (7%) coronary angiography. A total of 84 vessels were analysed. Mean age and sex were well matched (Kawasaki: 27±6.2 years; 13 males : 1 female vs. controls: 27±6.4 years; 13 males : 1 female). In patients with Kawasaki disease, thrombosed aneurysmal arteries were associated with a significantly impaired MPR compared to normal (mean Δ: -0.817; P=0.003) and aneurysmal (mean Δ: -0.957; P<0.001) arteries. MPR in aneurysmal and revascularised arteries were not significantly different from normal arteries in patients with Kawasaki disease. There was no significant difference in MPR between normal coronary arteries in patients with Kawasaki compared to controls. Conclusions Thrombosis in coronary aneurysms was associated with a significant impairment of myocardial perfusion in adult patients with convalescent Kawasaki disease. There was no significant reduction in perfusion in territories supplied by normal or aneurysmal arteries which does not support coronary microvascular dysfunction in these patients. Further studies are needed to confirm these preliminary findings.

Abstract 13332: Assessment of Myocardial Oxygenation Response to Vasoactive Breathing Maneuvers in Patients With Repaired Dextro-Transposition of the Great Arteries an OS-CMR Study

Introduction: Long-term outcomes of patients with repaired Dextro-transposition of the great arteries (D-TGA) by arterial switch operation (ASO) are excellent. However, studies have suggested impaired myocardial blood flow reserve. Oxygen-sensitive cardiac magnetic resonance (OS-CMR) with vasoactive breathing maneuvers (BM) offers a contrast-free tool for evaluating myocardial oxygenation. Hypothesis: Evaluate myocardial oxygenation reserve and microvascular function in repaired D-TGA post-ASO using OS-CMR with BM. Methods: In this single-center study, we analyzed OS-CMR images (basal and mid-left ventricular slices) of 9 D-TGA post-ASO patients (mean age 29 ±6.52yrs, 33.3% females) and 10 healthy participants (mean age 33 ±8.9 yrs, 40% females) who completed the BM. The BM consisted of free breathing, then hyperventilation, causing vasoconstriction, then breath hold, causing vasodilatation. End-systolic OS-CMR signal intensity (SI) was measured at baseline, after hyperventilation (closest to 0 sec of breath hold), and at closest to 30 sec of breath hold. Changes in SI (ΔSI) in % were calculated in response to the different periods and compared using independent samples t-test. Results: In the D-TGA cohort, the coronary response to hyperventilation was abnormal compared to healthy subjects (5.8±19.9% vs -15.1±13.3%, p=0.01). No difference was observed in ΔSI% during breath hold (mean TGA:3.0±10.5% vs mean healthy:5.7±6%, p=0.5). No differences were observed in mid-slices for either period. Conclusions: Our findings suggest patients with D-TGA may have an impaired vasoconstrictor response to a hyperventilation maneuver. Further studies should explore the associated pathophysiology and potential impact on clinical management.

Morphologic characteristic of rat myocardium in comorbid pathology

Diabetic cardiomyopathy is a serious complication of diabetes mellitus (DM). Aim. Therefore, we aimed to study myocardial changes in adult rats with streptozotocin (STZ)-induced DM exposed to chronic immobilization stress (CIS). Materials and methods. A total of 26 adult albino male rats weighing 180–200 g were examined. All the animals were divided into three groups: Group I included 10 rats with STZ-induced DM exposed to CIS; Group II comprised 10 rats with STZ-induced DM; Group III included 6 intact animals. The samples were collected on the 14th and 56th days of the experiment. Histological, histochemical, electron microscopy, and biochemical methods were used. Results. On the 14th day of the experiment, in Group I and Group II, increased blood flow was observed in the capillaries, venules, and veins, while an arteriolar spasm in the microcirculation was found. In addition, cardiomyocyte surface area in different myocardial regions reduced due to low glycogen content as confirmed by histochemical and ultrastructural studies. On the 56th day of the experiment, in Group I and Group II, hyperemia occurred due to red blood cell aggregation and microthrombi. The surface area of all microcirculatory vessels increased as compared to that of intact animals, as evidenced by an increase in their wall surface area leading to an increase in their wall-to-lumen ratio. Such morphometric changes in the microcirculatory vessels were indicative of decreased vascular permeability and impaired myocardial blood flow. At the histological level, in Group I and Group II, focal cardiomyocyte lysis, moderate to diffuse stromal edema, lymphohistiocytic infiltration were seen. Such changes pointed to sterile inflammation, probably due to myocardial infraction secondary to diabetic microangiopathy. In cardiomyocytes, karyolysis, vacuolar degeneration, apical ballooning, subsarcolemmic edema, fibrosis and lysis of myofibrils, colliquative necrosis were observed. Conclusions. STZ-induced DM and stress resulted in pronounced destructive changes in the myocardium of rats, including interstitial edema, focal cardiosclerosis, myolysis. Such changes occurred on the background developing diabetic microangiopathy. The most pronounced myocardial changes were recorded in animals with a comorbidity.

Relationship between impaired myocardial blood flow by positron emission tomography and low-attenuation plaque burden and pericoronary adipose tissue attenuation from coronary computed tomography: From the prospective PACIFIC trial

BackgroundPositron emission tomography (PET) is the clinical gold standard for quantifying myocardial blood flow (MBF). Pericoronary adipose tissue (PCAT) attenuation may detect vascular inflammation indirectly. We examined the relationship between MBF by PET and plaque burden and PCAT on coronary CT angiography (CCTA). MethodsThis post hoc analysis of the PACIFIC trial included 208 patients with suspected coronary artery disease (CAD) who underwent [15O]H2O PET and CCTA. Low-attenuation plaque (LAP, < 30HU), non-calcified plaque (NCP), and PCAT attenuation were measured by CCTA. ResultsIn 582 vessels, 211 (36.3%) had impaired per-vessel hyperemic MBF (≤ 2.30 mL/min/g). In multivariable analysis, LAP burden was independently and consistently associated with impaired hyperemic MBF (P = 0.016); over NCP burden (P = 0.997). Addition of LAP burden improved predictive performance for impaired hyperemic MBF from a model with CAD severity and calcified plaque burden (P < 0.001). There was no correlation between PCAT attenuation and hyperemic MBF (r = − 0.11), and PCAT attenuation was not associated with impaired hyperemic MBF in univariable or multivariable analysis of all vessels (P > 0.1). ConclusionIn patients with stable CAD, LAP burden was independently associated with impaired hyperemic MBF and a stronger predictor of impaired hyperemic MBF than NCP burden. There was no association between PCAT attenuation and hyperemic MBF.

Comparison of the prognostic value of impaired stress myocardial blood flow, myocardial flow reserve, and myocardial flow capacity on low-dose Rubidium-82 SiPM PET/CT

BackgroundThe most reliable quantitative variable on Rubidium-82 (82Rb) cardiac PET/CT for predicting major adverse cardiovascular events (MACE) has not been characterized with low-dose silicon photomultipliers (SiPM) technology, which allows halving injected activity and radiation dose delivering less than 1.0 mSv in a 70-kg individual. Methods and ResultsWe prospectively enrolled 234 consecutive participants with suspected myocardial ischemia. Participants underwent 82Rb cardiac SiPM PET/CT (5 MBq/kg) and were followed up for MACE over 652 days (interquartile range 559-751 days). For each participant, global stress myocardial blood flow (stress MBF), global myocardial flow reserve (MFR), and regional severely reduced myocardial flow capacity (MFCsevere) were measured. The Youden index was used to select optimal thresholds.In multivariate analysis after adjustments for clinical risk factors, reduced global stress MBF < 1.94 ml/min/g, reduced global MFR < 1.98, and regional MFCsevere > 3.2% of left ventricle emerged all as independent predictors of MACE (HR 4.5, 3.1, and 3.67, respectively, p < 0.001). However, only reduced global stress MBF remained an independent prognostic factor for MACE after adjusting for clinical risk factors and the combined use of global stress MBF, global MFR, and regional MFCsevere impairments (HR 2.81, p = 0.027). ConclusionUsing the latest SiPM PET technology with low-dose 82Rb halving the standard activity to deliver < 1 mSv for a 70-kg patient, impaired global stress MBF, global MFR, and regional MFC were powerful predictors of cardiovascular events, outperforming traditional cardiovascular risk factors. However, only reduced global stress MBF independently predicted MACE, being superior to global MFR and regional MFC impairments. Graphical Abstract▪

Apical Ischemia Is a Universal Feature of Apical Hypertrophic Cardiomyopathy.

Apical hypertrophic cardiomyopathy (ApHCM) accounts for ≈10% of hypertrophic cardiomyopathy cases and is characterized by apical hypertrophy, apical cavity obliteration, and tall ECG R waves with ischemic-looking deep T-wave inversion. These may be present even with <15 mm apical hypertrophy (relative ApHCM). Microvascular dysfunction is well described in hypertrophic cardiomyopathy. We hypothesized that apical perfusion defects would be common in ApHCM. A 2-center study using cardiovascular magnetic resonance short- and long-axis quantitative adenosine vasodilator stress perfusion mapping. One hundred patients with ApHCM (68 overt hypertrophy [≥15 mm] and 32 relative ApHCM) were compared with 50 patients with asymmetrical septal hypertrophy hypertrophic cardiomyopathy and 40 healthy volunteer controls. Perfusion was assessed visually and quantitatively as myocardial blood flow and myocardial perfusion reserve. Apical perfusion defects were present in all overt ApHCM patients (100%), all relative ApHCM patients (100%), 36% of asymmetrical septal hypertrophy hypertrophic cardiomyopathy, and 0% of healthy volunteers (P<0.001). In 10% of patients with ApHCM, perfusion defects were sufficiently apical that conventional short-axis views missed them. In 29%, stress myocardial blood flow fell below rest values. Stress myocardial blood flow was most impaired subendocardially, with greater hypertrophy or scar, and with apical aneurysms. Impaired apical myocardial blood flow was most strongly predicted by thicker apical segments (β-coefficient, -0.031 mL/g per min [CI, -0.06 to -0.01]; P=0.013), higher ejection fraction (-0.025 mL/g per min [CI, -0.04 to -0.01]; P<0.005), and ECG maximum R-wave height (-0.023 mL/g per min [CI, -0.04 to -0.01]; P<0.005). Apical perfusion defects are universally present in ApHCM at all stages. Its ubiquitous presence along with characteristic ECG suggests ischemia may play a disease-defining role in ApHCM.

Integration of quantitative absolute myocardial blood flow estimates from dynamic CZT-SPECT improves the detection of coronary artery disease

BackgroundBalanced ischemia with multi-vessel coronary artery disease (CAD) is difficult to diagnose with semiquantitative single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Dynamic cardiac SPECT provides quantitative estimations of stenosis severity and ischemic burden by assessing myocardial flow reserve (MFR) and myocardial blood flow (MBF). The aim of this study was to evaluate the incremental value of dynamic SPECT in multi-vessel coronary artery disease (CAD). MethodsPatients with suspected CAD who underwent dynamic ECG-gated dipyridamole MPI and coronary angiography within 6 months were retrospectively reviewed. The performance of summed stress, rest and difference scores (SSS, SRS, SDS), post-stress and resting MBF (MBFs, MBFr) and MFR were compared at both patient level and vessel level. ResultsIn 32 patients with 39 stenotic vessels, 12 had three-vessel disease (38%). Globally increased SSS and impaired MBF values were significantly associated with significant CAD at the patient level, but SDS and MFR were not. Regional increases in SSS and reductions in both MBFs and MBFr were significantly associated with stenotic vessels. The best cutoff value of global MBFs to predict CAD was 3.5 ml·g−1·min−1 (area under the curve, AUC = .84, P = .002). The best cutoff value of regional MBFs to detect significant stenosis was 3.6 ml·g−1·min−1 (AUC = .74, P < .001). However, the best possible cut-off values of MFR were not found. Sex-difference in both global and regional MBFr but MBFs was found, which might result in the non-significance in MFR. ConclusionsThis study validated a clinically available method to quantify MFR using dynamic CZT-SPECT. This method improved the detectability of multi-vessel CAD, and absolute MBFs was superior to MFR and other semiquantitative MPI parameters.

Mental Stress and Cardiovascular Health-Part I.

Epidemiological studies have shown that a substantial proportion of acute coronary events occur in individuals who lack the traditional high-risk cardiovascular (CV) profile. Mental stress is an emerging risk and prognostic factor for coronary artery disease and stroke, independently of conventional risk factors. It is associated with an increased rate of CV events. Acute mental stress may develop as a result of anger, fear, or job strain, as well as consequence of earthquakes or hurricanes. Chronic stress may develop as a result of long-term or repetitive stress exposure, such as job-related stress, low socioeconomic status, financial problems, depression, and type A and type D personality. While the response to acute mental stress may result in acute coronary events, the relationship of chronic stress with increased risk of coronary artery disease (CAD) is mainly due to acceleration of atherosclerosis. Emotionally stressful stimuli are processed by a network of cortical and subcortical brain regions, including the prefrontal cortex, insula, amygdala, hypothalamus, and hippocampus. This system is involved in the interpretation of relevance of environmental stimuli, according to individual’s memory, past experience, and current context. The brain transduces the cognitive process of emotional stimuli into hemodynamic, neuroendocrine, and immune changes, called fight or flight response, through the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. These changes may induce transient myocardial ischemia, defined as mental stress-induced myocardial ischemia (MSIMI) in patients with and without significant coronary obstruction. The clinical consequences may be angina, myocardial infarction, arrhythmias, and left ventricular dysfunction. Although MSIMI is associated with a substantial increase in CV mortality, it is usually underestimated because it arises without pain in most cases. MSIMI occurs at lower levels of cardiac work than exercise-induced ischemia, suggesting that the impairment of myocardial blood flow is mainly due to paradoxical coronary vasoconstriction and microvascular dysfunction.

Machine learning from quantitative coronary computed tomography angiography predicts ischemia and impaired myocardial blood flow

Abstract Background Atherosclerotic plaque characteristics influence the hemodynamic consequences of coronary lesions. This study sought to assess the performance of a machine learning (ML) score integrating coronary computed tomography angiography (CCTA)-based quantitative plaque features for the prediction of ischemia by invasive fractional flow reserve (FFR) and impaired myocardial blood flow (MBF) by [15O]H2O positron emission tomography (PET). Methods This post-hoc analysis of the PACIFIC (Prospective Comparison of Cardiac PET/CT, SPECT/CT Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography) trial included 208 patients with suspected coronary artery disease who underwent CCTA, [15O]H2O PET, and 3-vessel invasive FFR. Plaque quantification from CCTA was performed using semiautomated software. A boosted ensemble ML algorithm (XGBoost) trained on data from the NXT (Analysis of Coronary Blood Flow using CT Angiography: Next Steps) trial was used to develop a ML score for the prediction of per-vessel ischemia (invasive FFR ≤0.80). The performance of the ML score was evaluated in 551 vessels from the PACIFIC trial for external validation. Thereafter, we assessed the discriminative ability of the ML score for per-vessel impaired hyperemic MBF (≤2.30 mL/min/g). Results In total, 138 (25.0%) vessels had ischemia and 195 (35.4%) vessels had impaired hyperemic MBF. CCTA-derived quantitative percent diameter stenosis and low-density noncalcified plaque (LDNCP) volume were higher in ischemic vessels compared with non-ischemic vessels (60.8% vs. 19.9%; and 42.3 mm3 vs. 9.1 mm3; both p&amp;lt;0.001). The ML score demonstrated a significantly higher area under the receiver-operating characteristic curve (AUC) for predicting ischemia (0.92, 95% confidence interval [CI] 0.89–0.94) compared with visual stenosis grade (0.84, 95% CI 0.80–0.87; p&amp;lt;0.001). Overall, quantitative percent diameter stenosis and LDNCP volume had greatest feature importance for ML, followed by percent area stenosis, minimum luminal diameter, and contrast density drop (Figure 1). An individualized explanation of ML ischemia prediction is shown in Figure 2. When applied for impaired MBF discrimination, the ML score exhibited an AUC of 0.82 (95% CI 0.78–0.85) and was superior to visual stenosis grade (AUC 0.76, 95% CI 0.72–0.80; p=0.03). Conclusions An externally validated ML score integrating CCTA-based quantitative plaque features accurately predicts FFR-defined ischemia and abnormal MBF by PET, outperforming standard visual CCTA interpretation. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung, and Blood Institute, United States Performance of the ML scoreIndividual explanation of ML prediction

Myocardial Perfusion Defects in Hypertrophic Cardiomyopathy Mutation Carriers.

BackgroundImpaired myocardial blood flow (MBF) in the absence of epicardial coronary disease is a feature of hypertrophic cardiomyopathy (HCM). Although most evident in hypertrophied or scarred segments, reduced MBF can occur in apparently normal segments. We hypothesized that impaired MBF and myocardial perfusion reserve, quantified using perfusion mapping cardiac magnetic resonance, might occur in the absence of overt left ventricular hypertrophy (LVH) and late gadolinium enhancement, in mutation carriers without LVH criteria for HCM (genotype‐positive, left ventricular hypertrophy‐negative).Methods and ResultsA single center, case‐control study investigated MBF and myocardial perfusion reserve (the ratio of MBF at stress:rest), along with other pre‐phenotypic features of HCM. Individuals with genotype‐positive, left ventricular hypertrophy‐negative (n=50) with likely pathogenic/pathogenic variants and no evidence of LVH, and matched controls (n=28) underwent cardiac magnetic resonance. Cardiac magnetic resonance identified LVH‐fulfilling criteria for HCM in 5 patients who were excluded. Individuals with genotype‐positive, left ventricular hypertrophy‐negative had longer indexed anterior mitral valve leaflet length (12.52±2.1 versus 11.55±1.6 mm/m2, P=0.03), lower left ventricular end‐systolic volume (21.0±6.9 versus 26.7±6.2 mm/m2, P≤0.005) and higher left ventricular ejection fraction (71.9±5.5 versus 65.8±4.4%, P≤0.005). Maximum wall thickness was not significantly different (9.03±1.95 versus 8.37±1.2 mm, P=0.075), and no subject had significant late gadolinium enhancement (minor right ventricle‒insertion point late gadolinium enhancement only). Perfusion mapping demonstrated visual perfusion defects in 9 (20%) carriers versus 0 controls (P=0.011). These were almost all septal or near right ventricle insertion points. Globally, myocardial perfusion reserve was lower in carriers (2.77±0.83 versus 3.24±0.63, P=0.009), with a subendocardial:subepicardial myocardial perfusion reserve gradient (2.55±0.75 versus 3.2±0.65, P=<0.005; 3.01±0.96 versus 3.47±0.75, P=0.026) but equivalent MBF (2.75±0.82 versus 2.65±0.69 mL/g per min, P=0.826).ConclusionsRegional and global impaired myocardial perfusion can occur in HCM mutation carriers, in the absence of significant hypertrophy or scarring.

Machine Learning From Quantitative Coronary Computed Tomography Angiography Predicts Ischemia And Impaired Myocardial Blood Flow

Introduction: Atherosclerotic plaque characteristics may influence the hemodynamic consequences of coronary lesions. This study sought to assess the performance of a machine learning (ML) score integrating coronary computed tomography angiography (CCTA)-based quantitative plaque features for the prediction of ischemia by invasive fractional flow reserve (FFR) and impaired myocardial blood flow (MBF) by [15O]H2O positron emission tomography (PET).

Prediction of impaired myocardial blood flow (MBF) with the use of machine learning techniques on CTCA based parameters

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported in part from European Regional Development Fund, Operational Programme “Competitiveness, Entrepreneurship and Innovation 2014-2020 (EPAnEK)”, titled: The Greek Research Infrastructure for Personalized Medicine (pMED-GR) , no. GR 5002802 ,and by Greece and the European Union (European Social Fund-ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning 2014-2020» in the context of the project “Assessment of coronary atherosclerosis: a new complete, anatomo-functional, morphological and biomechanical approach”, Project no. 504776 Background Computed Tomography Coronary Angiography (CTCA) is a non-invasive imaging modality, used effectively for anatomo-functional assessment of coronary artery disease (CAD). Machine learning (ML) processes can effectively allow the extraction of useful information from multidimensional feature spaces for evaluation of coronary lesions. Purpose To investigate the ability of ML for predicting impaired myocardial blood flow (MBF) by combining computational fluid dynamics (CFD) derived parameters with quantitative plaque burden, plaque morphology and anatomical characteristics obtained from CTCA. Methods 53 patients (31 male, mean age 64.7 ± 7.1 years) with intermediate pre-test likelihood of CAD who underwent CTCA and PET-MPI were included. PET was considered positive when &amp;gt; 1 contiguous segment demonstrated MBF ≤ 2.3 mL/g/min for 15O-water or ≤ 1.79 for 13N-ammonia respectively. CFD derived parameters such as a previously validated, virtual functional assessment index (vFAI), segmental endothelial shear stress (ESS), as well as anatomical and plaque characteristics were assessed. Seven classifiers were implemented and internally validated using 5-fold cross validation, repeated 1000 times. Using sequential forward selection (SFS), the highest rank features combination, based on appearances in the highest mean area under curve (AUC) classification scheme, was selected and features performance was evaluated following exhaustive search (ES). Results 92 coronary segments were analyzed and 34 features derived from CTCA were extracted. Classifiers performance are depicted in Figure A. k-NN was the best classifier with AUCmean = 0.791 (SENSmean= 0.622, SPECmean = 0.840, p &amp;lt; 0.05). Clusters of features and number of appearances are presented in Figure B. The combination of vFAI, stenosis severity and lumen area demonstrated the highest AUC (1473 times). ES results are depicted in Figure C. The combination of vFAI and lumen area was the best predictor among all the combinations (AUCmean = 0.830, SENSmean =0.61, SPECmean =0.83, p &amp;lt; 0.05) followed by vFAI and stenosis severity (AUCmean = 0.81, SENSmean =0.72, SPECmean = 0.87, p &amp;lt; 0.05) and vFAI alone (AUCmean = 0.806, SENSmean =0.61, SPECmean =0.87, p &amp;lt; 0.05). Conclusion ML analysis is feasible for predicting with reasonable specificity abnormal MBF by PET, using a combination of CFD derived parameters and anatomical features. vFAI as a single characteristic was a specific predictor of impaired MBF, whilst in combination with stenosis severity, maintained almost the same AUC and specificity values and resulted in improved sensitivity. On the other hand, addition of lumen area to vFAI, increases the AUC and provides a relatively good specificity but low sensitivity. Abstract Figure 1

Myocardial Perfusion Simulation for Coronary Artery Disease: A Coupled Patient-Specific Multiscale Model

Patient-specific models of blood flow are being used clinically to diagnose and plan treatment for coronary artery disease. A remaining challenge is bridging scales from flow in arteries to the micro-circulation supplying the myocardium. Previously proposed models are descriptive rather than predictive and have not been applied to human data. The goal here is to develop a multiscale patient-specific model enabling blood flow simulation from large coronary arteries to myocardial tissue. Patient vasculatures are segmented from coronary computed tomography angiography data and extended from the image-based model down to the arteriole level using a space-filling forest of synthetic trees. Blood flow is modeled by coupling a 1D model of the coronary arteries to a single-compartment Darcy myocardium model. Simulated results on five patients with non-obstructive coronary artery disease compare overall well to [^{15}O]text {H}_{{2}}O PET exam data for both resting and hyperemic conditions. Results on a patient with severe obstructive disease link coronary artery narrowing with impaired myocardial blood flow, demonstrating the model’s ability to predict myocardial regions with perfusion deficit. This is the first report of a computational model for simulating blood flow from the epicardial coronary arteries to the left ventricle myocardium applied to and validated on human data.

Prognostic value of unrecognized myocardial infarction and hyperemic coronary sinus flow in patients undergoing elective percutaneous coronary intervention

Abstract Background Cardiac magnetic resonance (CMR) imaging is a useful instrument for the assessment of pathological and functional conditions without the need for ionizing radiation, radioactive tracers, or intravascular catheterization. Both unrecognized myocardial infarction (UMI) and impaired global myocardial blood flow (g-MBF) have been reported to be strongly associated with worse outcome in patients with cardiovascular disease. However, their combined efficacy remains undetermined. Purpose We sought to assess the prognostic value of the presence of UMI and pre-procedural hyperemic g-MBF evaluated by phase-contrast cine magnetic resonance imaging (PC-CMR) in patients with chronic coronary syndrome who underwent elective percutaneous coronary intervention (PCI). Methods A total of 177 patients with de novo functionally significant stenosis who underwent pre-PCI CMR and PCI between September, 2016 and March, 2019 were retrospectively studied. UMI was defined as a scar detected by late gadolinium enhancement (LGE) without previously diagnosed MI. g-MBF was assessed by quantifying coronary sinus flow using PC-CMR at rest and hyperemic state. The predictors of major adverse cardiac events (MACE; cardiac death, nonfatal myocardial infarction, clinically driven unplanned revascularization, or hospitalization for congestive heart failure) during follow-up were investigated. Results UMI was detected in 40 (27.7%) patients and rest and maximal hyperemic g-MBF evaluated by the coronary sinus flow obtained by PC-CMR were 0.95 ml/min/g and 2.26 ml/min/g, respectively. During the median follow-up of 26 months, cardiovascular death occurred in 1 patient (0.6%), nonfatal myocardial infarction occurred in 4 patients (2.3%), and clinically driven revascularization and hospitalization due to congestive heart failure occurred in 25 patients (14.1%) and 3 patients (1.7%) patients, respectively. In patients with MACE, hyperemic g-MBF was significantly lower and the prevalence of UMI were significantly higher compared with those without MACE (1.94 ml/min/g vs 2.36 ml/min/g P=0.014; 48.3% vs 23.6%, P=0.011). Cox proportional hazards model indicated that impaired hyperemic g-MBF (&amp;lt;2.00 ml/min/g) and the presence of UMI were significant predictors of MACE (HR 2.22, 95% CI 1.060–4.640, P=0.034; HR 2.660, 95% CI 1.290–5.470, P=0.008). During follow-up, cardiac event-free survival was significantly worse in patients with impaired hyperemic g-MBF (&amp;lt;2.00 ml/min/g) and UMI (log-rank χ2=11.0, P=0.010). Conclusion In patients with chronic coronary syndrome undergoing elective PCI, the combined assessment of UMI and hyperemic g-MBF obtained by preprocedural noninvasive CMR may provide significant prognostic information. Funding Acknowledgement Type of funding source: None

Coronary microvascular dysfunction results in impaired coronary flow reserve and altered oxygen balance in a swine model of INOCA with multiple risk factors

Abstract Introduction Comorbidities of ischemic heart disease, including diabetes mellitus (DM), hypercholesterolemia and chronic kidney disease (CKD), are associated with coronary microvascular dysfunction (CMD) and may contribute to myocardial “Ischemia and No Obstructive Coronary Artery disease” (INOCA). Purpose We studied myocardial perfusion and oxygen delivery using a novel swine model with multiple comorbidities. Methods DM (streptozotocin), HFD (high fat diet) and CKD (renal embolization), were induced in 12 female swine (DM+HFD+CKD), while 12 healthy female swine on a normal diet served as controls (CON). After 6 months, in the absence of coronary atherosclerosis, myocardial perfusion and function were studied at rest and during treadmill exercise. Results DM+HFD+CKD animals showed hyperglycemia, hypercholesterolemia and impaired kidney function. During exercise, DM+HFD+CKD demonstrated impaired myocardial blood flow and oxygen delivery, necessitating higher myocardial oxygen extraction (despite reduced capillary density), resulting in lower coronary venous oxygen levels, (Fig. 1). These perturbations were associated with lower myocardial efficiency, requiring higher oxygen consumption for a given level of myocardial work (Fig. 1), lower myocardial lactate consumption, stroke volume and LVdP/dtmax, suggestive of myocardial ischemia and dysfunction. Furthermore DM+HFD+CKD showed a reduction in adenosine-recruitable coronary flow reserve (2.69±0.26 vs 3.64±0.2 in CON, p&amp;lt;0.05), which was exclusively the result of an increase in basal coronary blood flow, while maximal coronary flow per gram of myocardium was maintained. The latter was consistent with the unchanged arteriolar wall/lumen ratio, arteriolar density and peri-arteriolar collagen content. eNOS blockade indicated loss of NO bioavailability in DM+HFD+CKD swine in vivo (Fig. 1), which was supported by blunted endothelium-dependent vasodilation to bradykinin in isolated small arteries. These findings suggest that changes in coronary microvascular function rather than structure contributed to the perturbations in myocardial oxygen delivery. Conclusion Common comorbidities result in CMD and impaired NO bioavailability rather than structural alterations in the microvasculature in swine, in the absence of appreciable atherosclerosis. These alterations are severe enough to produce perturbations in myocardial oxygen balance and coronary metabolism and function, particularly during exercise, resembling key features of INOCA. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): This study was supported by grants from the European Commission FP7-Health-2010 grant MEDIA-261409, the Netherlands CardioVascular Research Initiative: an initiative with support of the Dutch Heart Foundation [CVON2014-11 (RECONNECT)].

P6181The association of coronary lumen volume to left ventricle mass ratio with myocardial blood flow and fractional flow reserve

Abstract Background A low coronary lumen volume to left ventricle mass ratio (V/M) derived from coronary computed tomography angiography (CCTA) has been proposed as a factor contributing to impaired myocardial blood flow (MBF) even in the absence of obstructive coronary artery disease (CAD). Objective To elucidate the association of V/M with non-invasively obtained MBF parameters by means of [15O]H2O positron emission tomography (PET), as well as its correlations with invasively measured fractional flow reserve (FFR), overall and specifically in vessel with non-obstructive CAD. Methods This is a substudy of the PACIFIC trial, in which 208 patients underwent CCTA, and [15O]H2O PET prior to invasive coronary angiography (ICA) in conjunction with 3 vessel FFR measurements. Patient specific V/M was calculated for 152 patients. Matched vessel specific hyperemic MBF (hMBF), coronary flow reserve (CFR), FFR, and patient specific V/M were available for 431 vessels. The median V/M (20.71 mm3/g) was used to divide the study population into a group with a low V/M (&lt;20.71 mm3/g) and a high V/M (≥20.71 mm3/g). Non-obstructive CAD was defined as a ≤50% stenosis grade on ICA. Results Overall, a higher percentage of vessels with an abnormal hMBF (34% vs. 19%, p=0.009), lower FFR values (0.93 [interquartile range: 0.85–0.97] vs. 0.95 [0.89–0.98], p=0.016), and a higher number of positive FFR values (20% vs. 9%, p=0.004) were observed among vessels in the low V/M group. Furthermore, a weak correlation between V/M, global hMBF (R=0.179, p=0.027), and global CFR (R=0.163, p=0.045) as well as a weak significant association with vessel specific hMBF (p=0.027), and FFR (p&lt;0.001) was observed (figure 1). V/M was not independently predictive of vessels specific MBF parameters or FFR. Among vessels with non-obstructive CAD (361 vessels), an abnormal hMBF tended to be more frequently observed in vessels with a low patient specific V/M (21% vs. 13%, p=0.056). Globally, there was no correlation between V/M and hMBF nor CFR. Patient specific V/M tended to be weakly associated with vessel specific hMBF (p=0.083) and was associated with FFR (p=0.027) (figure 1). Lastly, patient specific V/M tended to be independently predictive of FFR in this specific group. Conclusion Overall, vessels with an abnormal hMBF, and positive FFR measurements were more frequently observed in patients with a low V/M compared to those with a high V/M. Furthermore, V/M weakly correlated with global hMBF as well as with CFR and was associated with vessel specific hMBF and FFR. However, there was no correlation between V/M and global nor vessel specific blood flow parameters in the absence of obstructive CAD, notwithstanding a weak association of V/M with FFR within this group was noted.

The association of coronary lumen volume to left ventricle mass ratio with myocardial blood flow and fractional flow reserve

BackgroundA diminished coronary lumen volume to left ventricle mass ratio (V/M) derived from coronary computed tomography angiography (CCTA) has been proposed as factor contributing to impaired myocardial blood flow (MBF) even in the absence of obstructive disease on invasive coronary angiography (ICA). MethodsPatients underwent CCTA, and positron emission tomography (PET) prior to ICA. Matched global V/M, global, and vessel specific hyperaemic MBF (hMBF), coronary flow reserve (CFR), and, FFR were available for 431 vessels in 152 patients. The median V/M (20.71 mm3/g) was used to divide the population into patients with either a low V/M or a high V/M. ResultsOverall, a higher percentage of vessels with an abnormal hMBF and FFR (34% vs. 19%, p = 0.009 and 20% vs. 9%, p = 0.004), as well as a lower FFR (0.93 [interquartile range: 0.85–0.97] vs. 0.95 [0.89–0.98], p = 0.016) values were observed in the low V/M group. V/M was weakly associated with vessel specific hMBF (R = 0.148, p = 0.027), and FFR (R = 0.156, p < 0.001). Among vessels with non-obstructive CAD on ICA (361 vessels), no association between V/M and vessel specific hMBF nor CFR was noted. However, in the absence of obstructive CAD, V/M was associated with (R = 0.081, p = 0.027), and independently predictive for FFR (p = 0.047). ConclusionOverall, an abnormal vessel specific hMBF and FFR were more prevalent in patients with a low V/M compared to those with a high V/M. Furthermore, V/M was weakly associated with vessel specific hMBF and FFR. In the absence of obstructive CAD on ICA, V/M was weakly associated with notwithstanding independently predictive for FFR.

Cardiac Autonomic Function Is Associated With Myocardial Flow Reserve in Type 1 Diabetes.

The link between cardiac autonomic neuropathy and risk of cardiovascular disease is highlighted as an area in which research is needed. This study was undertaken to evaluate the association between measures of cardiac autonomic function and cardiac vascular function in type 1 diabetes using new and sensitive methods. This was a cross-sectional study in patients with type 1 diabetes, stratified by normoalbuminuria (n = 30) and macroalbuminuria (n = 30), and in healthy control subjects (n = 30). Cardiac autonomic function was evaluated using heart rate variability (HRV) indices, cardiovascular autonomic reflex tests (CARTs), and cardiac 123I-metaiodobenzylguanidine (MIBG) imaging. Cardiac vascular function was assessed as myocardial flow reserve (MFR) measured by cardiac 82Rb-positron emission tomography/computed tomography. The measures of cardiac autonomic function (except low frequency-to-high frequency ratio and the Valsalva test ratio) were positively correlated to MFR in unadjusted analysis. All the HRV indices lost significance after adjustment for age and heart rate. After further adjustment for relevant cardiovascular risk factors, the late heart-to-mediastinum ratio directly measuring the function of adrenergic receptors and sympathetic integrity (from the MIBG scintigraphy) and the 30-to-15 ratio (a CART), remained positively associated with MFR (P ≤ 0.04). Cardiac autonomic dysfunction, including loss of cardiac sympathetic integrity in type 1 diabetes, is associated with and may contribute to impaired myocardial blood flow regulation.

Assessment of Coronary Microcirculation During Cardiac Catheterization.

Functional tests used in the catheterization laboratory have emerged as a very important adjunctive tool to coronary angiography that can identify patients with myocardial blood flow impairment. Fractional Flow Reserve (FFR) measurement is highly recommended for detection of ischemia-related coronary lesion(s) when objective evidence of vessel-related ischemia is not available. Recently, the much simpler instantaneous wave free ratio (iFR) was proposed as an alternative to FFR without the requirement for administration of vasodilators. More user-friendly techniques like iFR might further contribute to value-based care in coronary interventions.

Non-contrast assessment of microvascular integrity using arterial spin labeled cardiovascular magnetic resonance in a porcine model of acute myocardial infarction

BackgroundFollowing acute myocardial infarction (AMI), microvascular integrity and function may be compromised as a result of microvascular obstruction (MVO) and vasodilator dysfunction. It has been observed that both infarcted and remote myocardial territories may exhibit impaired myocardial blood flow (MBF) patterns associated with an abnormal vasodilator response. Arterial spin labeled (ASL) CMR is a novel non-contrast technique that can quantitatively measure MBF. This study investigates the feasibility of ASL-CMR to assess MVO and vasodilator response in swine.MethodsThirty-one swine were included in this study. Resting ASL-CMR was performed on 24 healthy swine (baseline group). A subset of 13 swine from the baseline group underwent stress ASL-CMR to assess vasodilator response. Fifteen swine were subjected to a 90-min left anterior descending (LAD) coronary artery occlusion followed by reperfusion. Resting ASL-CMR was performed post-AMI at 1–2 days (N = 9, of which 6 were from the baseline group), 1–2 weeks (N = 8, of which 4 were from the day 1–2 group), and 4 weeks (N = 4, of which 2 were from the week 1–2 group). Resting first-pass CMR and late gadolinium enhancement (LGE) were performed post-AMI for reference.ResultsAt rest, regional MBF and physiological noise measured from ASL-CMR were 1.08 ± 0.62 and 0.15 ± 0.10 ml/g/min, respectively. Regional MBF increased to 1.47 ± 0.62 ml/g/min with dipyridamole vasodilation (P < 0.001). Significant reduction in MBF was found in the infarcted region 1–2 days, 1–2 weeks, and 4 weeks post-AMI compared to baseline (P < 0.03). This was consistent with perfusion deficit seen on first-pass CMR and with MVO seen on LGE. There were no significant differences between measured MBF in the remote regions pre and post-AMI (P > 0.60).ConclusionsASL-CMR can assess vasodilator response in healthy swine and detect significant reduction in regional MBF at rest following AMI. ASL-CMR is an alternative to gadolinium-based techniques for assessment of MVO and microvascular integrity within infarcted, as well as salvageable and remote myocardium. This has the potential to provide early indications of adverse remodeling processes post-ischemia.