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Multiphoton microscopy. (A) 3D images for convex and concave regions of 20-and 52-week-old Fbln5 −/− aortas, shown here for selected axial-circumferential slices at specimen-specific in vivo axial stretch and 80 mmHg. Collagen appeared as undulated bundles with a preferential orientation in the adventitia; elastin-based structures were irregular and scattered in all regions, as expected with the absence of fibulin-5. (B) Mean thickness of the wall and adventitia obtained from multiple 3D images (age groups merged) at three physiologic pressures and the sample-specific axial in vivo axial stretch (see fig. S5, age effects). Adventitial thicknesses were normalized by, and thus independent of, overall wall thickness, which was lower in convex than in concave regions, with a higher fraction of adventitia in convex compared to concave regions and, consequently, the opposite for the medial fraction. (C) Orientation dispersion of collagen fibers determined for concave and convex regions at three different physiologic pressures and the sample-specific axial in vivo stretch. Higher dispersion manifested in the convex region compared to the concave regions in 20-week Fbln5 −/− , while 52-week Fbln5 −/− had higher dispersion in concave regions. Aging increased the fiber orientation dispersion. Significance denoted by *P < 0.05.
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Arterial tortuosity manifests in many conditions, including hypertension, genetic mutations predisposing to thoracic aortopathy, and vascular aging. Despite evidence that tortuosity disrupts efficient blood flow and that it may be an important clinical biomarker, underlying mechanisms remain poorly understood but are widely appreciated to be largel...
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... (i.e., the normal aorta stores elastic energy during systole and uses this energy during diastole to work on the blood to augment flow), circumferential material stiffness appears to be highly mechanoregulated within the arterial wall (12). There was little correlation between tortuosity and either circumferential or axial material stiffness ( fig. S4), suggesting that the intramural cells were yet able to sense and regulate the stiffness of the matrix on average. Figure 3 contrasts calculated values of circumferential and axial stretch and similarly biaxial material stiffness within concave and convex regions of the tortuous aorta in Fbln5 −/− mice. Notwithstanding considerable ...
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... microscopy-both second-harmonic generation revealing fibrillar collagen and autofluorescence revealing elastinbased structures-provided complementary information on local microstructure. The medial layer appeared nonuniform and scattered in the Fbln5 −/− aorta due to agglomerations containing irregular-shaped elastin (Fig. 4A), not compact lamellar structures, Fig. 1. pDIC data collection and analysis. (A) Representative in situ image (photo credit: Dar Weiss, Yale University) of a tortuous descending thoracic aorta at zero blood pressure (arrow) in a 20-week-old Fbln5 −/− mouse, which was excised and (B) mounted on a custom triple-needle assembly for ...
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... well-organized elastic fiber networks as in normal vessels; there were, however, no apparent differences in smooth muscle cell density between the concave and convex regions ( fig. S5). Overall wall thickness was lower in convex compared with concave regions of the tortuous Fbln5 −/− aorta (Fig. 4B), with loaded thickness significantly less in 52-than 20-week-old samples ( fig. S5). Yet, the convex regions had a significantly (P < 0.05) thicker adventitia than did the concave regions, with adventitial fraction not different in 20-and 52-week-old Fbln5 −/− ...
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... adventitial layer in the tortuous Fbln5 −/− aortas consists of multiple layers of fibrillar collagen bundles inclined toward a primary orientation that corresponds, at the in vivo axial stretch and physiological distending pressures, with the overall axial direction of the vessel (Fig. 4A), consistent with previous observations (13). Although this primary orientation did not differ significantly, upon pressurization, between the convex and concave regions or between the 20-and 52-week Fbln5 −/− mice, the degree of dispersion of fiber orientation around the primary direction did vary (Fig. 4C), with collagen fibers ...
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... overall axial direction of the vessel (Fig. 4A), consistent with previous observations (13). Although this primary orientation did not differ significantly, upon pressurization, between the convex and concave regions or between the 20-and 52-week Fbln5 −/− mice, the degree of dispersion of fiber orientation around the primary direction did vary (Fig. 4C), with collagen fibers dispersed significantly more in convex compared to concave regions in the 20-week-old Fbln5 −/− samples, while this characteristic was inverted in 52-week-old Fbln5 −/− samples, with a higher dispersion of the fibers in concave regions. The orientation dispersion increased with pressure in most regions, indicating ...
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... once tortuosity has developed (see Fig. 5, top left), a responsive change in the maximal regional orientation of diagonal fibers from the convex toward the concave regions (left to right, simulating the inverted trend for the dispersion of collagen fibers observed for 52-week-old Fbln5 −/− samples relative to 20-week-old Fbln5 −/− samples; see Fig. 4C) cannot resolve the permanent tortuosity of this compromised, yet axially unloaded, computational aorta. This last finding suggests that arteries that have grown and remodeled into a marked tortuous pattern may be mechanobiologically and structurally stable against possible reverse remodeling, even if new spatial nonuniformities are ...
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... For scenarios in which the actomyosin or elastin networks were removed, the pressure-force effect persisted, indicating that the mechanical behavior of the tissue remains largely unaffected by the absence of these networks in this context. The no-elastin result is inconsistent with the observation that removal of elastin leads to greater vessel tortuosity (Weiss et al. 2020;Berman et al. 2022), suggesting something inaccurate or incomplete in the current model. Our cylinder model imposes a specific amount of axial stretch, assumes that the entire artery expands radially in the same way (i.e., the shape becomes a larger cylinder rather than bulging), and does not permit Fig. 7 Pressure-force relationship in the pressure-force test for a networks without actomyosin, b networks without elastin, and c networks with only half the original collagen content any deviation from the cylindrical shape (e.g., buckling (Lee et al. 2012)), so it cannot produce a tortuous vessel geometry. ...
The arterial wall is a structurally complex material, exhibiting both nonlinearity and anisotropy in its mechanics, with the compelling consequence that the end plate force in a pressure-stretch experiment can increase or decrease with pressure depending on the axial stretch of the vessel. Furthermore, it has long been observed that the axial stretch at which the ex vivo pressure-force curve is flat is close to the in vivo axial stretch, but the mechanism driving this phenomenon has remained unclear. By employing and modifying a custom plugin that represents tissue components as networks, we computationally tested the hypothesis that tensional homeostasis at the microscopic scale could lead to the macroscopic pressure-invariant axial force effect observed at in vivo axial stretch. Our findings suggest that remodeling events for individual fibers to achieve a target stress can, acting in aggregate, cause the vessel to exhibit a pressure-invariant axial force in the pressure-force experiment without any explicit sensing of the pressure-force behavior during remodeling. Computational isolation of tissue components suggested that remodeling of collagen fibers is a primary driver of this result. Further as long seen experimentally, the pressure-force curve plateau occurred at stretches close to the in vivo remodeling stretch.
... (both total arterioles and arterioles that extend into layer 6/corpus callosum) in aged brains compared to the young adult mice (Fig. 5D). However, we observed highly tortuous (twisted) vessels across the entire cortex ( Fig. 5E; highlighted with red arrowheads), which is consistent with prior observations in aged animals and humans 51,52 . Further analysis revealed that aged animals demonstrate increased arteriole tortuosity, as measured by the arc chord ratio (Fig. 5F) (see Methods for more details). ...
Aging is frequently associated with compromised cerebrovasculature and pericytes. However, we do not know how normal aging differentially impacts vascular structure and function in different brain areas. Here we utilize mesoscale microscopy methods and in vivo imaging to determine detailed changes in aged murine cerebrovascular networks. Whole-brain vascular tracing shows an overall ~10% decrease in vascular length and branching density with ~7% increase in vascular radii in aged brains. Light sheet imaging with 3D immunolabeling reveals increased arteriole tortuosity of aged brains. Notably, vasculature and pericyte densities show selective and significant reductions in the deep cortical layers, hippocampal network, and basal forebrain areas. We find increased blood extravasation, implying compromised blood-brain barrier function in aged brains. Moreover, in vivo imaging in awake mice demonstrates reduced baseline and on-demand blood oxygenation despite relatively intact neurovascular coupling. Collectively, we uncover regional vulnerabilities of cerebrovascular network and physiological changes that can mediate cognitive decline in normal aging.
... A thorough literature review discovered that this arterial variation closely resembled the arterial morphology observed in tortuous dilatation, characterised by tortuous, dilated, and elongated arteries, among other features. However, this condition is typically observed in the vertebral-basilar arteries and carotid arteries and is associated with hypertension, hyperlipaemia, atherosclerosis, and other related factors [6,21,23]. ...
BACKGROUND: The superficial palmar arch is a crucial blood supply to the palm. However, it exhibits significant variations, posing challenges in surgical procedures. Gaining a comprehensive understanding of the relationship between different types, physiological indices, and the clinical significance of the superficial palmar arch will enhance the accuracy of diagnosing and treating patients. MATERIALS AND METHODS: In this study, we dissected a total of 72 specimens, comprising 39 males and 33 females. We observed the type, length, and diameter of the superficial palmar arch and analysed its correlation with the disease. Additionally, we conducted Doppler ultrasound measurements on 20 healthy volunteers (10 males and 10 females) and 18 patients with superficial palmar arch injury (10 males and 8 females) to assess the classification, diameter, intimal thickness, and blood flow velocity of the superficial palmar arch. We collected information on 9 male patients with finger fractures and observed the classification of the superficial palmar arch, fracture healing time, and basic function recovery time. Lastly, we analysed rare variant specimens encountered during the anatomy process. RESULTS: In the exploration of human anatomy, there were 4 types of superficial palmar arch: ulnar artery arch type in 17 cases (23.61%), radial ulnar artery type in 46 cases (63.89%), ulnar artery without arch type in 6 cases (8.33%), and 3 cases (4.17%) of double arch type of radial and ulnar artery. One case of nonarched type was found in an imaging examination (5%). In one elderly male specimen, the hand’s superficial palmar arch artery was tortuous and dilated. In addition, there was a positive correlation between the diameter and length of the superficial palmar arch (except the second common palmar digital artery in women), among which the ulnar artery and the third common palmar digital artery had the strongest correlation. Compared to healthy volunteers, patients with ulnar injury in the radial-ulnar artery type exhibited a decrease in the diameter and blood flow velocity of the ulnar artery, as well as the second and third common palmar digital arteries. No such change was observed in patients with radial injury. Additionally, patients with ulnar injury in other types of radial-ulnar artery also experienced a decrease in the diameter and blood flow velocity of the ulnar artery. Finger fracture patients with ulnar artery with arch and ulnar artery without arch had shorter fracture healing time and basic function recovery time compared to those with radial-ulnar artery type. CONCLUSIONS: This study investigated the relationship between the classification, physiological index, and clinical significance of the superficial palmar arch at all levels. The results demonstrated that when the superficial palmar arch is damaged, it is important to consider both the classification and the site of damage, because this potentially results in improved therapeutic outcomes. These findings provide a basis for future clinical research.
... In a broader sense, capturing full-field soft tissue deformation is critical for a number of research applications ranging from inverse material characterization [54][55][56][57], to high-fidelity biomechanical modeling of in vivo mechanisms [58][59][60], and patient-specific modeling and We briefly note here that "Type 1" and "Type 3" represent 3D culture platforms while "Type 2" portrays a significantly thinner (almost 2D) platform. We elaborate more on each type in the "Experimental data" Section and in S2 Appendix. ...
Advancing human induced pluripotent stem cell derived cardiomyocyte (hiPSC-CM) technology will lead to significant progress ranging from disease modeling, to drug discovery, to regenerative tissue engineering. Yet, alongside these potential opportunities comes a critical challenge: attaining mature hiPSC-CM tissues. At present, there are multiple techniques to promote maturity of hiPSC-CMs including physical platforms and cell culture protocols. However, when it comes to making quantitative comparisons of functional behavior, there are limited options for reliably and reproducibly computing functional metrics that are suitable for direct cross-system comparison. In addition, the current standard functional metrics obtained from time-lapse images of cardiac microbundle contraction reported in the field (i.e., post forces, average tissue stress) do not take full advantage of the available information present in these data (i.e., full-field tissue displacements and strains). Thus, we present “MicroBundleCompute,” a computational framework for automatic quantification of morphology-based mechanical metrics from movies of cardiac microbundles. Briefly, this computational framework offers tools for automatic tissue segmentation, tracking, and analysis of brightfield and phase contrast movies of beating cardiac microbundles. It is straightforward to implement, runs without user intervention, requires minimal input parameter setting selection, and is computationally inexpensive. In this paper, we describe the methods underlying this computational framework, show the results of our extensive validation studies, and demonstrate the utility of exploring heterogeneous tissue deformations and strains as functional metrics. With this manuscript, we disseminate “MicroBundleCompute” as an open-source computational tool with the aim of making automated quantitative analysis of beating cardiac microbundles more accessible to the community.
... The description of viscous fluid motion in a curved channel is a complex problem in theoretical hydrodynamics [1] and has significant relevance in various applications, such as hemodynamics [2][3][4] and pipeline transport [5]. Channel curvature leads to a rearrangement of flow topology, the formation of vortex flows, and closed vortex zones. ...
This study explores the problem of describing viscous fluid motion for Navier–Stokes equations in curved channels, which is important in applications like hemodynamics and pipeline transport. Channel curvature leads to vortex flows and closed vortex zones. Asymptotic models of the flux problem are useful for describing viscous fluid motion in long pipes, thus considering geometric parameters like pipe diameter and characteristic length. This study provides a representation for the vorticity vector and energy dissipation in the flow problem for a curved channel, thereby determining the magnitude of vorticity and energy dissipation depending on the channel’s central line curvature and torsion. The accuracy of the asymptotic formulas are estimated in terms of small parameter powers. Numerical calculations for helical tubes demonstrate the effectiveness of the asymptotic formulas.
... Another advantage is that it can be applied to specimens with any surface shape (curved or planar) and offers the possibility to make accurate measurements on cylindrical structures such as blood vessels. It can be used to measure strains on specimens subjected to out-of-plane bending or twisting, which has been reported for aortas (Weiss et al., 2020). Last but not least, the technique can achieve a point-to-point strain accuracy of up to 0.001 and a full-field average strain accuracy on the order of 50 Â 10 À6 , allowing both small and large deformation responses to be studied in a single specimen. ...
... In a broader sense, capturing full-field soft tissue deformation is critical for a number of research applications ranging from inverse material characterization [54,55,56,57], to high-fidelity biomechanical modeling of in vivo mechanisms [58,59,60], and patient-specific modeling and procedure planning [61,62]. And recently, there has been keen interest in implementing image registration-based techniques widely used in the field of computer vision [54,63] for fullfield measurements, including digital image correlation (DIC) [64,65,66,67,68], 3D-DIC [69,70], digital volume correlation (DVC) [71,72,73,74], and optical flow algorithms [75,76,77]. ...
Advancing human induced pluripotent stem cell derived cardiomyocyte (hiPSC-CM) technology will lead to significant progress ranging from disease modeling, to drug discovery, to regenerative tissue engineering. Yet, alongside these potential opportunities comes a critical challenge: attaining mature hiPSC-CM tissues. At present, there are multiple techniques to promote maturity of hiPSC-CMs including physical platforms and cell culture protocols. However, when it comes to making quantitative comparisons of functional behavior, there are limited options for reliably and reproducibly computing functional metrics that are suitable for direct cross-system comparison. In addition, the current standard functional metrics obtained from time-lapse images of cardiac microbundle contraction reported in the field (i.e., post forces, average tissue stress) do not take full advantage of the available information present in these data (i.e., full-field tissue displacements and strains). Thus, we present "MicroBundleCompute," a computational framework for automatic quantification of morphology-based mechanical metrics from movies of cardiac microbundles. Briefly, this computational framework offers tools for automatic tissue segmentation, tracking, and analysis of brightfield and phase contrast movies of beating cardiac microbundles. It is straightforward to implement, requires little to no parameter tuning, and runs quickly on a personal computer. In this paper, we describe the methods underlying this computational framework, show the results of our extensive validation studies, and demonstrate the utility of exploring heterogeneous tissue deformations and strains as functional metrics. With this manuscript, we disseminate "MicroBundleCompute" as an open-source computational tool with the aim of making automated quantitative analysis of beating cardiac microbundles more accessible to the community.
... Figure S1 shows the sequence of histomechanical tests, which were necessarily limited to mice that survived a scheduled 4-week study. We used 2 custom ex vivo testing devices to independently quantify bulk 19 and regional 20,21 aortic segments were cannulated with custom glass micropipettes through the aortic valve (proximal end) and brachiocephalic artery (distal end), secured with 6-O sutures, and placed within a computer-controlled testing device in a Hanks' buffered salt solution at room temperature to ensure passive responses. The computer preconditioned the specimens cyclically from 10 to 120 mm Hg while maintaining fixed the energetically preferred (in vivo) axial stretch, λ iv z , then subjected the specimens to a sequence of 7 protocols: cyclic pressurization from 10 to 140 mm Hg at 3 fixed axial stretches (λ iv z and ±5% of this value) and cyclic axial loading from 0 to f max at 4 fixed luminal pressures (10, 60, 100, and 140 mm Hg), where f max (in mN) was the specimen-specific value at 140 mm Hg and 1.05 λ iv z . ...
... Local optical coherence tomography (OCT)-derived thicknesses collected at 100 cross-sections along the length of the vessel were mapped onto the pDIC-reconstructed geometry using an automatic coregistration pipeline. 22 Detailed information about our multimodality pDIC and OCT pipeline can be found elsewhere, 20,21,23 noting that collecting over 1000 data points at 42 mechanical states yields >42 000 data points per sample. Hence, the pDIC comparisons were based on over 42 000×23=966 000 data points, again exploiting the strategy of increasing the data collected per sample while reducing variability by using highly protocolized, high-resolution methods. ...
... 22 Once completed, the final set of identified parameters at each element was used to compute full-field distributions of the different mechanical metrics, as described previously. 21,22,26 To perform spatially local statistical analyses of group-wise differences in geometric and mechanical properties, we developed an automatic pipeline to parametrize and coregister all pDIC+OCT-derived data. Starting from each vessel-specific quadrilateral patch obtained from pDIC, we performed a principal component analysis of nodal coordinates and automatically identified 2 objective landmarks on the vessel ( Figure S3): the outermost point on the outer curvature and point of ligation on the distal end. ...
Background:
Transmural failure of the aorta is responsible for substantial morbidity and mortality; it occurs when mechanical stress exceeds strength. The aortic root and ascending aorta are susceptible to dissection and rupture in Marfan syndrome, a connective tissue disorder characterized by a progressive reduction in elastic fiber integrity. Whereas competent elastic fibers endow the aorta with compliance and resilience, cross-linked collagen fibers confer stiffness and strength. We hypothesized that postnatal reductions in matrix cross-linking increase aortopathy when turnover rates are high.
Methods:
We combined ex vivo biaxial mechanical testing with multimodality histological examinations to quantify expected age- and sex-dependent structural vulnerability of the ascending aorta in Fbn1C1041G/+ Marfan versus wild-type mice without and with 4-week exposures to β-aminopropionitrile, an inhibitor of lysyl oxidase-mediated cross-linking of newly synthesized elastic and collagen fibers.
Results:
We found a strong β-aminopropionitrile-associated sexual dimorphism in aortic dilatation in Marfan mice and aortic rupture in wild-type mice, with dilatation correlating with compromised elastic fiber integrity and rupture correlating with compromised collagen fibril organization. A lower incidence of rupture of β-aminopropionitrile-exposed Marfan aortas associated with increased lysyl oxidase, suggesting a compensatory remodeling of collagen that slows disease progression in the otherwise compromised Fbn1C1041G/+ aorta.
Conclusions:
Collagen fiber structure and function in the Marfan aorta are augmented, in part, by increased lysyl oxidase in female and especially male mice, which improves structural integrity, particularly via fibrils in the adventitia. Preserving or promoting collagen cross-linking may represent a therapeutic target for an otherwise vulnerable aorta.
... Our previous studies have demonstrated that arteries can also buckle and deform into curved shapes due to elevated pressure, reduced axial tension, or wall degeneration (Han 2007;Han 2012;Lee et al. 2012;Martinez and Han 2012;Zhang et al. 2014). Artery buckling is a possible mechanism for the development of tortuous arteries (Han 2009a;Goriely and Vandiver 2010;Liu and Han 2013;Zhang et al. 2014;Weiss et al. 2020). Similar to tortuosity, artery buckling could hinder the blood flow leading to ischemia to distal organs or trigger thrombosis (Chesnutt and Han 2011;Han 2012). ...
Artery buckling occurs due to hypertensive lumen pressure or reduced axial tension and other pathological conditions. Since arteries in vivo often experience axial twisting and the collagen fiber alignment in the arterial wall may become nonsymmetric, it is imperative to know how axial twisting and nonsymmetric collagen alignment would affect the buckling behavior of arteries. To this end, the objective of this study was to determine the effect of axial twisting and nonsymmetric collagen fiber distribution on the critical pressure of arterial bent buckling. The buckling model analysis was generalized to incorporate an axial twist angle and nonsymmetric fiber alignment. The effect of axial twisting on the critical pressure was simulated and experimentally tested in a group of porcine carotid arteries. Our results showed that axial twisting tends to reduce the critical pressure depending on the axial stretch ratio and twist angle. In addition, nonsymmetric fiber alignment reduces the critical pressure. Experimental results confirmed that a twist angle of 90° reduces the critical pressure significantly (p < 0.05). It was concluded that axial twisting and non-axisymmetric collagen fibers distribution could make arteries prone to bent buckling. These results enrich our understanding of artery buckling and vessel tortuosity. The model analysis and results could also be applicable to other fiber reinforced tubes under lumen pressure and axial twisting.
... Te study protocol was approved by the Ethics Committee of Nihon University Itabashi Hospital (RK-201121-01) and was in accordance with the ethical standards of the institutional research committee and the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. [14], and therefore, the angle of the left subclavian artery in the thorax was measured as an indicator of the tortuosity with the following method (Figures 2(a) and 2(b)). Te coronal plane image from the point where the bifurcation of the vertebral artery as a geographic landmark in the thorax was used for the measurement of the left subclavian artery. ...
... In the most recent study, the right subclavian artery tortuosity has been defned as experimental manipulation difculty [25]. Measurements at the points of angulation of the intracerebral vasculature from magnetic resonance angiography images can partly evaluate the arterial tortuosity [26], and an experimental computational model has indicated that the angles difer as a result of the tortuosity [14]. Because the tortuosity of an artery is difcult to assess with angiography, those prior reports [14,26] have shown that our new method that quantitatively assesses the left subclavian artery angle on CT imaging is an indicator of the artery tortuosity. ...
... Measurements at the points of angulation of the intracerebral vasculature from magnetic resonance angiography images can partly evaluate the arterial tortuosity [26], and an experimental computational model has indicated that the angles difer as a result of the tortuosity [14]. Because the tortuosity of an artery is difcult to assess with angiography, those prior reports [14,26] have shown that our new method that quantitatively assesses the left subclavian artery angle on CT imaging is an indicator of the artery tortuosity. We do not believe that CT scans prior to cardiac catheterization are necessary for all patients with ACS. ...
Background:
The effect of left subclavian artery tortuosity during percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) remains unclear.
Methods:
Of 245 ACS patients (from November 2019 and May 2021), 79 who underwent PCI via a left radial approach (LRA) were included. We measured the angle of the left subclavian artery in the coronal view on CT imaging as an indicator of the tortuosity and investigated the association between that angle and the clinical variables and procedural time.
Results:
Patients with a left subclavian artery angle of a median of <70 degrees (severe tortuosity) were older (75.4 ± 11.7 vs. 62.9 ± 12.3 years, P < 0.001) and had a higher prevalence of female sex (42.1% vs. 14.6%, P=0.007), hypertension (94.7% vs. 75.6%, P=0.02), and subclavian artery calcification (73.7% vs. 34.2%, P < 0.001) than those with that ≥70 degrees. The left subclavian artery angle correlated negatively with the sheath cannulation to the first balloon time (ρ = -0.51, P < 0.001) and total procedural time (ρ = -0.32, P=0.004). A multiple linear regression analysis revealed that the natural log transformation of the sheath insertion to first balloon time was associated with a subclavian artery angle of <70 degrees (β = 0.45, P < 0.001).
Conclusion:
Our study showed that lower left subclavian artery angles as a marker of the tortuosity via the LRA were strongly associated with a longer sheath insertion to balloon time and subsequent entire procedure time during the PCI.
