Entire Coronary Vasculature Research Articles

Effects of Coronary Stenosis on Coronary Vascular Impedance

Introduction: The impedance analysis for circulation system is a powerful tool to comprehensively measure the afterload of the entire circulation system. The spectrum of vascular mechanical parameters derived from the impedance analysis can reveal the compliance and resistance changes in proximal and distal vessels, as well as the wave reflections. However, the similar investigation in the opposition of the coronary circulation is limited, and it is unknown how coronary stenosis affects the vascular impedance of the coronary circulation. In this study, we aimed to quantify and compare the changes in the vascular impedance of coronary circulation from the dynamic pressure and flow relations in healthy and patients with stenosis. Method: The pressure and flow rate waveforms from the main coronary artery were obtained from a lumped-parameter computational model that coupled the systemic circulation with the coronary perfusion within a closed system. Both healthy and diseased (coronary stenosis) pressure-flow relations were examined. A Fourier transform was performed to analyze the pressure and flow data, and the resistance (Z0), characteristic impedance (ZC), wave reflections (RW), total arterial compliance (C), and other hemodynamic parameters were derived. Results: Compared to the healthy subject, the diseased subject presented an increased resistance (Z0 was elevated from 0.44 mmHg ▪ min/ml to 0.59 mmHg ▪ min/ml), increased characteristic impedance (ZC was elevated from 0.07 mmHg ▪ min/ml to 0.14 mmHg ▪ min/ml), and reduced wave reflection (RW was decreased from 0.72 to 0.6). These changes indicate elevated distal arteries and arterioles narrowing and proximal artery stiffening in the entire coronary vasculature. Moreover, the coronary flow and the total arterial compliance (stroke volume divided by pulse pressure) were reduced with the disease progression. These data suggest a reduced coronary perfusion and stiffening of the artery in the coronary circulation. Discussion: The impedance analysis has been widely used for systemic and pulmonary circulations previously to quantify the total afterload of the left and right ventricles, respectively. The distribution of the impedance in different frequencies reflects the anatomical and mechanical properties of the vasculature in the circulation system. This study originally found that the coronary artery impedance is altered by coronary stenosis. The key characteristics include the narrowing of distal coronary arteries and stiffening of proximal coronary arteries. However, since both proximal and distal arteries are altered, the wave reflection was reduced, and this may explain a reduced pulse pressure observed in the diseased subject. The reduction in overall coronary perfusion indicates an impaired blood supply to the ventricle and may be responsible for the dysfunction of the heart. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A preliminary coronary computed tomography angiography-based study of perivascular fat attenuation index: relation with epicardial adipose tissue and its distribution over the entire coronary vasculature.

To investigate the perivascular fat attenuation index (FAI) in association with epicardial adipose tissue (EAT) parameters and its distribution over the entire coronary vasculature in patients with known or suspected coronary artery disease (CAD). Patients with known or suspected CAD who underwent coronary computed tomography angiography from January 1, 2019, to June 1, 2019, were retrospectively included. The perivascular FAI was quantified on four main epicardial coronary arteries and seven coronary segments. Moreover, EAT density and volume were measured. We included 192 consecutive patients (55 without coronary plaque [mean age 46.4 ± 13.2 years, 69.1% male] and 137 with coronary plaque [mean age 57.9 ± 13.0 years, 84.7% male]). EAT density was lower than perivascular FAI in both groups, but they exhibited substantial correlation (- 83.33 ± 4.54 vs. - 78.22 ± 6.52 HU, p < 0.001; r = 0.667 in plaque- patients and - 83.11 ± 4.48 vs. - 77.81 ± 5.63 HU, p < 0.001; r = 0.778 in plaque+ patients). The left main coronary artery had the highest perivascular FAI, followed by the left circumflex artery. The perivascular FAI in proximal segments was significantly higher compared to that in distal segments (all p < 0.05). Furthermore, the presence of plaque did not alter perivascular FAI on the patient or segmental level. The perivascular FAI was significantly higher than EAT density and correlated substantially with EAT density. The perivascular FAI distribution over the entire coronary tree varied and prompted for vessel-specific or segment-specific thresholds to determine abnormal perivascular FAI in practice. • The perivascular FAI correlated well with EAT density and had higher values than EAT density. • The distributions of perivascular FAI differ between coronary vessels or segments; considering segment and vessel confounding factors while conducting a perivascular FAI study is necessary. • No significant difference of perivascular FAI was observed between patients without and with coronary plaque, nor between coronary segments without plaque and those with plaque.

Enhancing cardiovascular research with whole-organ imaging.

There have been tremendous advances in the tools available for surveying blood vessels within whole organs and tissues. Here, we summarize some of the recent developments in methods for immunolabeling and imaging whole organs and provide a protocol optimized for the heart. Multiple protocols have been established for chemically clearing large organs and variations are compatible with cell type-specific labeling. Heart tissue can be successfully cleared to reveal the three-dimensional structure of the entire coronary vasculature in neonatal and adult mice. Obtaining vascular reconstructions requires exceptionally large imaging files and new computational methods to process the data for accurate vascular quantifications. This is a continually advancing field that has revolutionized our ability to acquire data on larger samples as a faster rate. Historically, cardiovascular research has relied heavily on histological analyses that use tissue sections, which usually sample cellular phenotypes in small regions and lack information on whole tissue-level organization. This approach can be modified to survey whole organs but image acquisition and analysis time can become unreasonable. In recent years, whole-organ immunolabeling and clearing methods have emerged as a workable solution, and new microscopy modalities, such as light-sheet microscopy, significantly improve image acquisition times. These innovations make studying the vasculature in the context of the whole organ widely available and promise to reveal fascinating new cellular behaviors in adult tissues and during repair.

Advances in Quantitative Analysis of 18F-Sodium Fluoride Coronary Imaging.

18F-sodium fluoride (18F-NaF) positron emission tomography (PET) has emerged as a promising noninvasive imaging tool for the assessment of active calcification processes in coronary artery disease. 18F-NaF uptake colocalizes to high-risk and ruptured atherosclerotic plaques. Most recently, 18F-NaF coronary uptake was shown to be a robust and independent predictor of myocardial infarction in patients with advanced coronary artery disease. In this review, we provide an overview of the advances in coronary 18F-NaF imaging. In particular, we discuss the recently developed and validated motion correction techniques which address heart contractions, tidal breathing, and patient repositioning during the prolonged PET acquisitions. Additionally, we discuss a novel quantification approach—the coronary microcalcification activity (which has been inspired by the widely employed method in oncology total active tumor volume measurement). This new method provides a single number encompassing 18F-NaF activity within the entire coronary vasculature rather than just information regarding a single area of most intense tracer uptake.

Whole-vessel coronary 18F-sodium fluoride PET for assessment of the global coronary microcalcification burden.

18F-sodium fluoride (18F-NaF) has shown promise in assessing disease activity in coronary arteries, but currently used measures of activity - such as maximum target to background ratio (TBRmax) - are defined by single pixel count values. We aimed to develop a novel coronary-specific measure of 18F-NaF PET reflecting activity throughout the entire coronary vasculature (coronary microcalcification activity [CMA]). Patients with recent myocardial infarction and multi-vessel coronary artery disease underwent 18F-NaF PET and coronary CT angiography. We assessed the association between coronary 18F-NaF uptake (both TBRmax and CMA) and coronary artery calcium scores (CACS) as well as low attenuation plaque (LAP, attenuation < 30 Hounsfield units) volume. In 50 patients (64% males, 63 ± 7years), CMA and TBRmax were higher in vessels with LAP compared to those without LAP (1.09 [0.02, 2.34] versus 0.0 [0.0, 0.0], p < 0.001 and 1.23 [1.16, 1.37] versus 1.04 [0.93, 1.11], p < 0.001). Compared to a TBRmax threshold of 1.25, CMA > 0 had a higher diagnostic accuracy for detection of LAP: sensitivity of 93.1 (83.3-98.1)% versus 58.6 (44.9-71.4)% and a specificity of 95.7 (88.0-99.1)% versus 80.0 (68.7-88.6)% (both p < 0.001). 18F-NaF uptake assessed by CMA correlated more closely with LAP (r = 0.86, p < 0.001) than the CT calcium score (r = 0.39, p < 0.001), with these associations outperforming those observed for TBRmax values (LAP r = 0.63, p < 0.001; CT calcium score r = 0.30, p < 0.001). Automated assessment of disease activity across the entire coronary vasculature is feasible using 18F-NaF CMA, providing a single measurement that has closer agreement with CT markers of plaque vulnerability than more traditional measures of plaque activity.

Effects of coronary revascularization on global coronary flow reserve in stable coronary artery disease.

AimsCoronary flow reserve (CFR) is an integrated measure of the entire coronary vasculature, and is a powerful prognostic marker in coronary artery disease (CAD). The extent to which coronary revascularization can improve CFR is unclear. This study aimed to evaluate the impact of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) on CFR in patients with stable CAD.Methods and resultsIn a prospective, multicentre observational study, CFR was measured by 15O-water positron emission tomography as the ratio of stress to rest myocardial blood flow at baseline and 6 months after optimal medical therapy (OMT) alone, PCI, or CABG. Changes in the SYNTAX and Leaman scores were angiographically evaluated as indicators of completeness of revascularization. Follow-up was completed by 75 (25 OMT alone, 28 PCI, and 22 CABG) out of 82 patients. The median SYNTAX and Leaman scores, and baseline CFR were 14.5 [interquartile range (IQR): 8–24.5], 5.5 (IQR: 2.5–12.5), and 1.94 (IQR: 1.67–2.66), respectively. Baseline CFR was negatively correlated with the SYNTAX (ρ = −0.40, P < 0.001) and Leaman scores (ρ = −0.33, P = 0.004). Overall, only CABG was associated with a significant increase in CFR [1.67 (IQR: 1.14–1.96) vs. 1.98 (IQR: 1.60–2.39), P < 0.001]. Among patients with CFR <2.0 (n = 41), CFR significantly increased in the PCI [1.70 (IQR: 1.42–1.79) vs. 2.21 (IQR: 1.78–2.49), P = 0.002, P < 0.001 for interaction between time and CFR] and CABG groups [1.28 (IQR: 1.13–1.80) vs. 1.86 (IQR: 1.57–2.22), P < 0.001]. The reduction in SYNTAX or Leaman scores after PCI or CABG was independently associated with the percent increase in CFR after adjusting for baseline characteristics (P = 0.012 and P = 0.011, respectively).ConclusionCoronary revascularization ameliorated reduced CFR in patients with obstructive CAD. The degree of improvement in angiographic CAD burden by revascularization was correlated with magnitude of improvement in CFR.

Coronary Plaque Burden at Coronary CT Angiography in Asymptomatic Men and Women.

Purpose To assess the relationship between total, calcified, and noncalcified coronary plaque burdens throughout the entire coronary vasculature at coronary computed tomographic (CT) angiography in relationship to cardiovascular risk factors in asymptomatic individuals with low-to-moderate risk. Materials and Methods This HIPAA-compliant study had institutional review board approval, and written informed consent was obtained. Two hundred two subjects were recruited to an ongoing prospective study designed to evaluate the effect of HMG-CoA reductase inhibitors on atherosclerosis. Eligible subjects were asymptomatic individuals older than 55 years who were eligible for statin therapy. Coronary CT angiography was performed by using a 320-detector row scanner. Coronary wall thickness and plaque were evaluated in all epicardial coronary arteries greater than 2 mm in diameter. Images were analyzed by using dedicated software involving an adaptive lumen attenuation algorithm. Total plaque index (calcified plus noncalcified plaque) was defined as plaque volume divided by vessel length. Multivariable regression analysis was performed to determine the relationship between risk factors and plaque indexes. Results The mean age of the subjects was 65.5 years ± 6.9 (standard deviation) (36% women), and the median coronary artery calcium (CAC) score was 73 (interquartile range, 1-434). The total coronary plaque index was higher in men than in women (42.06 mm(2) ± 9.22 vs 34.33 mm(2) ± 8.35; P < .001). In multivariable analysis controlling for all risk factors, total plaque index remained higher in men than in women (by 5.01 mm(2); P = .03) and in those with higher simvastatin doses (by 0.44 mm(2)/10 mg simvastatin dose equivalent; P = .02). Noncalcified plaque index was positively correlated with systolic blood pressure (β = 0.80 mm(2)/10 mm Hg; P = .03), diabetes (β = 4.47 mm(2); P = .03), and low-density lipoprotein (LDL) cholesterol level (β = 0.04 mm(2)/mg/dL; P = .02); the association with LDL cholesterol level remained significant (P = .02) after additional adjustment for the CAC score. Conclusion LDL cholesterol level, systolic blood pressure, and diabetes were associated with noncalcified plaque burden at coronary CT angiography in asymptomatic individuals with low-to-moderate risk. (©) RSNA, 2015 Online supplemental material is available for this article.

A full 3-D reconstruction of the entire porcine coronary vasculature.

We have previously reconstructed the entire coronary arterial tree of the porcine heart down to the first segment of capillaries. Here, we extend the vascular model through the capillary bed and the entire coronary venous system. The reconstruction was based on comprehensive morphometric data previously measured in the porcine heart. The reconstruction was formulated as a large-scale optimization process, subject to both global constraints relating to the location of the larger veins and to local constraints of measured morphological features. The venous network was partitioned into epicardial, transmural, and perfusion functional subnetworks. The epicardial portion was generated by a simulated annealing search for the optimal coverage of the area perfused by the arterial epicardial vessels. The epicardial subnetwork and coronary arterial capillary network served as boundary conditions for the reconstruction of the in-between transmural and perfusion networks, which were generated to optimize vascular homogeneity. Five sets of full coronary trees, which spanned the entire network down to the capillary level, were reconstructed. The total number of reconstructed venous segments was 17,148,946 ± 1,049,498 (n = 5), which spanned the coronary sinus (order -12) to the first segment of the venous capillary (order 0v). Combined with the reconstructed arterial network, the number of vessel segments for the entire coronary network added up to 27,307,376 ± 1,155,359 (n = 5). The reconstructed full coronary vascular network agreed with the gross anatomy of coronary networks in terms of structure, location of major vessels, and measured morphometric statistics of native coronary networks. This is the first full model of the entire coronary vasculature, which can serve as a foundation for realistic large-scale coronary flow analysis.

The Role of Serum Response Factor in Early Coronary Vasculogenesis

Defects in vascular development are a major cause of fetal demise and congenital cardiovascular disease. Knowledge is scarce concerning both embryonic vascular cell progenitors and the underlying regulatory mechanisms that determine their commitment to various vessel cell lineages. During early cardiovascular development, the proepicardium (PE) is the major source of vascular progenitors. The PE is a transient embryonic structure found at stages 16 and 17 in the chick, at 9.5 days postcoitum (dpc) in the mouse, and at approximately 5 weeks in the human that consists of mesothelial and mesenchymal cells overlying the septum transversum (ST). Cells within the PE undergo a complex process of development and differentiation that involves at least two directed waves of migration and epithelial-to-mesenchymal transitions (EMT). The PE cells make contact with the inferior surface of the developing myocardium, migrate over the surface of the heart forming the epicardium, and penetrate into the myocardium and give rise to subepicardial mesenchymal cells (SEMCs). The SEMCs subsequently migrate throughout the developing heart giving rise to the entire coronary vasculature consisting of fibroblasts as well as endothelial and smooth muscle cells [32]. Serum response factor (SRF) is essential for mesoderm formation during embryonic development [2]. A necessary role for SRF in the development of vascular smooth muscle from yet to be characterized PE-derived coronary vascular precursor cells has been demonstrated in avian explant models [15]. The role of SRF in vivo during some of the earliest steps in mammalian PE-mediated vascular development, however, is less well studied, and our recent observations suggest that it likely is more complex. This brief review aims to discuss the role of SRF during early coronary vasculogenesis as it relates to development of the PE.

Extensive Cardiac Allograft Vasculitis and Concurrent Fat Necrosis 6 Years After Orthotopic Heart Transplantation

Coronary artery vasculitis has been described as a rare lesion in the spectrum of transplant vasculopathy or as an extension of severe acute cellular rejection. We describe a patient, 6 years after orthotopic cardiac transplantation, who developed rapid heart failure and died despite aggressive treatment, minimal cardiac rejection (ISHLT Grade 1R), and no known transplant vasculopathy. Autopsy showed a diffuse and essentially complete necrotizing vasculitis of the entire coronary vasculature involving small, medium and large vessels, with extensive fat necrosis within the pericardial space. Macrophages of the M2 phenotype were found lining the major coronary vascular lumens and infiltrating their walls. The presence of the M2 macrophage phenotype supports transplant vasculitis as part of the chronic transplant vasculopathy continuum.

A Novel Method for Visualization of Entire Coronary Arterial Tree

The complexity of the coronary circulation especially in the deep layers largely evades experimental investigations. Hence, virtual/computational models depicting structure-function relation of the entire coronary vasculature including the deep layer are imperative. In order to interpret such anatomically based models, fast and efficient visualization algorithms are essential. The complexity of such models, which include vessels from the large proximal coronary arteries and veins down to the capillary level (3 orders of magnitude difference in diameter), is a challenging visualization problem since the resulting geometrical representation consists of millions of vessel segments. In this study, a novel method for rendering the entire porcine coronary arterial tree down to the first segments of capillaries interactively is described which employs geometry reduction and occlusion culling techniques. Due to the tree-shaped nature of the vasculature, these techniques exploit the geometrical topology of the object to achieve a faster rendering speed while still handling the full complexity of the data. We found a significant increase in performance combined with a more accurate, gap-less representation of the vessel segments resulting in a more interactive visualization and analysis tool for the entire coronary arterial tree. The proposed techniques can also be applied to similar data structures, such as neuronal trees, airway structures, bile ducts, and other tree-like structures. The utility and future applications of the proposed algorithms are explored.

Bifurcation asymmetry of the porcine coronary vasculature and its implications on coronary flow heterogeneity

The branching pattern of the coronary arteries and veins is asymmetric, i.e., many small vessels branch off of a large trunk such that the two daughter vessels at a bifurcation are of unequal diameters and lengths. One important implication of the geometric vascular asymmetry is the dispersion of blood flow at a bifurcation, which leads to large spatial heterogeneity of myocardial blood flow. To document the asymmetric branching pattern of the coronary vessels, we computed an asymmetry ratio for the diameters and lengths of all vessels, defined as the ratio of the daughter diameters and lengths, respectively. Previous data from silicone elastomer cast of the entire coronary vasculature including arteries, arterioles, venules, and veins were analyzed. Data on smaller vessels were obtained from histological specimens by optical sectioning, whereas data on larger vessels were obtained from vascular casts. Asymmetry ratios for vascular areas, volumes, resistances, and flows of the various daughter vessels were computed from the asymmetry ratios of diameters and lengths for every order of mother vessel. The results show that the largest orders of arterial and venous vessels are most asymmetric and the degree of asymmetry decreases toward the smaller vessels. Furthermore, the diameter asymmetry at a bifurcation is significantly larger for the coronary veins (1.7-6.8 for sinus veins) than the corresponding arteries (1.5-5.8 for left anterior descending coronary artery) for orders 2-10, respectively. The reported diameter asymmetry at a bifurcation leads to significant heterogeneity of blood flow at a bifurcation. Hence, the present data quantify the dispersion of blood flow at a bifurcation and are essential for understanding flow heterogeneity in the coronary circulation.

Long-term prevention of premature coronary atherosclerosis in homozygous familial hypercholesterolemia

Homozygous familial hypercholesterolemia (FHH) leads to severe premature atherosclerosis. A 22-year-old woman with FHH has been treated with a combination of H.E.L.P. apheresis (heparin-mediated extracorporeal LDL precipitation) and statins for 15 years. The combined treatment maintained a plasma LDL-cholesterol reduction from baseline of 840 to 122 mg/dL (85% reduction). In addition, H.E.L.P. apheresis reduced the elevated lipoprotein(a) and fibrinogen levels by 60% to 70%. All xanthomata disappeared. There is no evidence of premature atherosclerosis studied by means of electron beam computed tomography and 13N-ammonia positron emission tomography: The entire coronary vasculature is free of calcifications. Her myocardial blood flow at rest (87 mL/100 g/min) and during stress (308 mL/100 g/min) and the coronary flow reserve (3.5) are normal after H.E.L.P. treatment. This case demonstrates the efficacy and safety of the combined treatment of H.E.L.P. apheresis and statins even in serious cases of FHH. (J Pediatr 2002;141:125-8)

The coronary vasculature and its reconstruction.

Recently, we have developed several new innovations in the morphometry of vascular trees. These innovations have been used to study the anatomy of the coronary circulation in the pig and have yielded a complete set of morphometric data on the entire coronary vasculature. Since, the innovations are applicable to any organ that has a tree-like vasculature, their utility in describing the quantitative anatomy of intraorgan vasculature is evident. These advancements in morphometry along with the automation of vascular tree reconstruction, data analysis, and hemodynamic applications should make the data base on intraorgan vasculature more abundant and more useful. The morphometric data will contribute to the Circulatory Network Physiome that will serve as an anatomical basis for the Physiome Project. This article covers several topics: (1) intraorgan vascular trees in terms of their anatomy, mechanical properties, physiological behavior, and adaptation, (2) reconstruction of the coronary vasculature, and (3) some of the shortcomings of the present morphometric data base and some proposed remedies. Finally, a discussion of the constitution of the circulatory network physiome in terms of the available morphometric data on intraorgan vasculature will be presented.