Hemodynamic Theory Research Articles

The site-specific distribution of atheromatous plaques in the coronary arteries.

The etiology of atherosclerosis is still unknown, but there are several hypotheses trying to explain this complex disease. Most consider atherosclerosis as a cholesterol storage disease. However, hypercholesterolemia is not a cause but a risk factor. Besides, like other well-known systemic risk factors, it does not explain the uneven distribution of atheromatous plaques in the vasculature. Atherosclerotic lesions develop mainly at vulnerable "risk points" of the arterial wall such as curvatures and near side branches, and predominantly in the left anterior descending (LAD), while the left circumflex (LCx) artery is relatively spared. Furthermore, atheromatous plaques are present mainly in the proximal segments in the LAD and LCx, in contrast to the right coronary artery (RCA), where plaques are more evenly distributed. The hemodynamic theory explains to some extent the distribution of atherosclerotic lesions and considers atherosclerosis as a reactive biological response of endothelial cells to wall shear stress. In this review, we discuss the interplay of concentration of low-density lipoproteins at the luminal surface and local hemodynamic forces (disturbed flow) that reduce wall shear stress in the process of plaque formation. Moreover, we present the distribution of atheromatous plaques in the coronary arteries in autopsy studies and imaging methods such as cardiac computed tomography angiography and invasive coronary angiography.

Electromagnetism, Blood Flow and Coagulation

There is a lot of uncertainty in the theory of hemodynamics. The amount of work need to displace the blood in the systemic circulation, exceeds the work done by the left ventricle. With this, blood recovers increased flow resistance between the heartbeats with the Womersley number alterations in the rhythm of the accompanying electrocardiogram (ECG). Viscoelastic transformation is heavily expressed in coagulation. There must be a relationship between the ECG and blood transient flow resistance. The influence of the electromagnetic field on blood coagulation was studied. Venous blood was affected by the oscillated electromagnetic field (500 - 5000 Hz), with the square wave input signal in 25 healthy individuals (15 males, 10 females in the age 18 - 57 years). Electromagnetic irradiation (EMI) time of the sample 3 - 10 min. Hypocoagulation in normal blood samples was revealed (decreased quantity of Platelets up to 10 - 23 × 109/L, Prothrombin index up to 9% - 10%, Fibrinogen concentration up to 0.20 - 0.21 g/L) and thrombolysis after the blood stasis. Ac electric field from the myocardial depolarization initiates electroacoustic phenomena. An emerging repulsing electromagnetic force acts on the red blood cells (RBC) and in addition to the pulse pressure from the heart, promotes blood motion and viscoelastic changes. The alterations of the blood inertial and elasticity, in addition to hemodynamics, are facilitated by the magnetic features of the hemoglobin. The external electromagnetic signal can manage the blood coagulation process, including thrombolysis.

Does the Leaflet Fusion Subtype Affect Pattern and Rate of Growth in BAV Aortopathy?: A Study of 102 BAV Aortopathy Cases With A Literature Review

Bicuspid aortic valves (BAV) and related aortopathy remain an intriguing topic. Not all BAVs get diseased and around 40% would develop aortic dilatation in their lifetime. If haemodynamic theory is to be believed, then leaflet fusion pattern should have an impact. This study sought to compare the association of aortic morphologies and rate of growth in a set of 102 BAV acropathies operated at a single centre, based on the fusion patterns. Data on aortic valve replacements over a 10-year period was analysed from a prospectively maintained database. Of the 198 BAV undergoing surgery, 102 had aortic dilatation above 40 mm on echocardiogram. These underwent computed tomography (CT) aortograms and were followed up as a part of a database. The impact of leaflet fusion patterns on aortic dilatation pattern and rate was analysed. Of the 102, two patients had type 0 pathology and one had left-noncoronary (LN) leaflet fusion. Seventy-four (74) had type 1A or left-right (RL) fusion and 25 had type 1B right-noncoronary (RN) fusion. RL fusion had more males, were taller, bigger and had more proportion of aortic stenosis (AS). Aortic diameters, angles and growth rates at root, ascending/descending aorta and arch were not different. Regression analyses for size or growth did not show any significant impact of fusion pattern. Left-right fusion pattern comprised three-quarters of BAV in this cohort and these patients were bigger, taller and had a greater proportion of males with increased rate of aortic stenosis. Despite these differences, there was no significant impact of fusion pattern on aortic size or rate of growth.

Acute Effects of Different Intensities of Cycling Acute Exercise on Carotid Arterial Apparent Elasticity and Hemodynamic Variables.

Background Cardiovascular disease (CVD) is closely related to arterial elasticity and hemodynamics. Exercises have been reported to immediately decrease arterial apparent elasticity and regulate hemodynamic variables. However, the relationship between them and exercise intensity remains elusive. The purpose of this study was to determine the acute effects of different intensities of acute cycling exercise on carotid arterial apparent elasticity and hemodynamics. Methods 32 healthy men (age: 19.4 ± 0.6 years) attended the laboratory on five occasions and completed cycling acute exercise for 20 minutes at five intensities (40%, 50%, 60%, 70%, and 80% heart rate reserve (HRR)). At the right carotid artery, center-line velocity and arterial inner diameter waveforms were examined before and immediately after exercise. Based upon the measured data, the classical hemodynamic theory was used to calculate the apparent elasticity and the local hemodynamic variables. Results The arterial apparent stiffness and the apparent elastic modulus following acute cycling exercise at 60% to 80% HRR were significantly higher than baseline. The mean center-line velocity accelerated from 50% to 80% HRR, but no intensity of intervention altered mean blood flow. Immediately after intervention, the mean wall shear stress and oscillatory shear index increased. Conclusions Aerobic cycling intervention, with intensity from 40% to 80% HRR, did not change the brain blood supply. A bout of cycling intervention decreased apparent elasticity, and there was an intensity-dependent effect on apparent elasticity and hemodynamic variables. This study would provide referable data for the further study on the effects of aerobic exercise on arterial hemodynamics and elasticity and underlying physiological mechanisms.

Physiologic blood flow is turbulent

Contemporary paradigm of peripheral and intracranial vascular hemodynamics considers physiologic blood flow to be laminar. Transition to turbulence is considered as a driving factor for numerous diseases such as atherosclerosis, stenosis and aneurysm. Recently, turbulent flow patterns were detected in intracranial aneurysm at Reynolds number below 400 both in vitro and in silico. Blood flow is multiharmonic with considerable frequency spectra and its transition to turbulence cannot be characterized by the current transition theory of monoharmonic pulsatile flow. Thus, we decided to explore the origins of such long-standing assumption of physiologic blood flow laminarity. Here, we hypothesize that the inherited dynamics of blood flow in main arteries dictate the existence of turbulence in physiologic conditions. To illustrate our hypothesis, we have used methods and tools from chaos theory, hydrodynamic stability theory and fluid dynamics to explore the existence of turbulence in physiologic blood flow. Our investigation shows that blood flow, both as described by the Navier–Stokes equation and in vivo, exhibits three major characteristics of turbulence. Womersley’s exact solution of the Navier–Stokes equation has been used with the flow waveforms from HaeMod database, to offer reproducible evidence for our findings, as well as evidence from Doppler ultrasound measurements from healthy volunteers who are some of the authors. We evidently show that physiologic blood flow is: (1) sensitive to initial conditions, (2) in global hydrodynamic instability and (3) undergoes kinetic energy cascade of non-Kolmogorov type. We propose a novel modification of the theory of vascular hemodynamics that calls for rethinking the hemodynamic–biologic links that govern physiologic and pathologic processes.

Spontaneous appearance of de novo intracranial arteriovenous malformation in hepatic cirrhosis

BackgroundIntracranial arteriovenous malformations (AVMs) are rare lesions that can be congenital or acquired in early childhood, with fatal outcome in approximately 30% of cases. De novo formation during adulthood without established predisposing vascular pathology or previous brain insult is even less frequent. Case DescriptionWe present a case of de novo brain AVM in an alcoholic Child-B cirrhosis setting. Thirty previously reported cases presented de novo AVM in patients of all ages that had another previous brain pathology or insult, such as AVM resection. Seventeen of those cases occurred in adult patients, with only 2 showing no significant predisposing factor. The present pathophysiological review covers and completes Mullan's hemodynamic “two-hit” model, associating probable thrombotic predisposition to AVM with brain insult triggering a later stage based on angiogenic stimuli. ConclusionsThis case report and literature review renews previously discussed hemodynamic theories and contributes to a fuller understanding of the pathogenesis and progression of AVM. We postulate a causal link between hepatopathy and de novo AVM, which should be strengthened and interpreted based on recent genetic data and future prospective studies.

Comment on "Radial and longitudinal motion of the arterial wall: Their relation to pulsatile pressure and flow in the artery".

Most researchers derived the arterial pressure-wave equation by taking the axial blood flow as the major mechanism and assumed the flow motion was governed by the Navier-Stokes equation. However, only realistic hemodynamic theory can help to develop method for future healthcare. Here, we pointed out a different rigorous hemodynamic model that explained many physiological facts. Our previous work started directly from Newton's law by deriving the radial and the axial momentum equations of the elastic arterial wall system and of the enclosed blood system, with the contact forces between the two systems being counted explicitly. Our model has some important applications in future healthcare, such as providing a basis for studying the collective behavior of the cardiovascular system and developing quantitative methods for disease prevention and diagnosis.

Did you know developing quantitative pulse diagnosis with realistic haemodynamic theory can pave a way for future personalized health care

Did you know developing quantitative pulse diagnosis with realistic haemodynamic theory can pave a way for future personalized health care

A Research Based on Hemodynamic Model for Heart-Mural Coronary Artery-Myocardial Bridge

An experimental model for heart-mural coronary artery-myocardial bridge was established based on the theory of hemodynamics. The application of the model demonstrated that it can repeat to great extent the phenomenon of myocardial bridge compressing mural coronary artery that results in abnormal hemodynamic characteristic. The in vitro simulation experiment indicates that the anomaly of normal stress, circumferential stress and wall shear stress mainly occurs in the proximal end. As the oppression level increases, the mean proximal stress and the oscillatory value (maximum-minimum) increase obviously. The experimental model for heart-mural coronary artery-myocardial bridge provides a method to study relationship between myocardial bridge and atherosclerosis.

Haemodynamic assessment of bicuspid aortic valve aortopathy: a systematic review of the current literature.

Both genetic and haemodynamic theories explain the aetiology, progression and optimal management of bicuspid aortic valve aortopathy. In recent years, the haemodynamic theory has been explored with the help of magnetic resonance imaging and computational fluid dynamics. The objective of this review was to summarize the findings of these investigations with focus on the blood flow pattern and associated variables, including flow eccentricity, helicity, flow displacement, cusp opening angle, systolic flow angle, wall shear stress (WSS) and oscillatory shear index. A structured literature review was performed from January 1990 to January 2018 and revealed the following 3 main findings: (i) the bicuspid aortic valve is associated with flow eccentricity and helicity in the ascending aorta compared to healthy and diseased tricuspid aortic valve, (ii) flow displacement is easier to obtain than WSS and has been shown to correlate with valve morphology and type of aortopathy and (iii) the stenotic bicuspid aortic valve is associated with elevated WSS along the greater curvature of the ascending aorta, where aortic dilatation and aortic wall thinning are commonly found. We conclude that new haemodynamic variables should complement ascending aorta diameter as an indicator for disease progression and the type and timing of intervention. WSS describes the force that blood flow exerts on the vessel wall as a function of viscosity and geometry of the vessel, making it a potentially more reliable marker of disease progression.

Enlightening the Association between Bicuspid Aortic Valve and Aortopathy.

Bicuspid aortic valve (BAV) patients have an increased incidence of developing aortic dilation. Despite its importance, the pathogenesis of aortopathy in BAV is still largely undetermined. Nowadays, intense focus falls both on BAV morphology and progression of valvular dysfunction and on the development of aortic dilation. However, less is known about the relationship between aortic valve morphology and aortic dilation. A better understanding of the molecular pathways involved in the homeostasis of the aortic wall, including the extracellular matrix, the plasticity of the vascular smooth cells, TGFβ signaling, and epigenetic dysregulation, is key to enlighten the mechanisms underpinning BAV-aortopathy development and progression. To date, there are two main theories on this subject, i.e., the genetic and the hemodynamic theory, with an ongoing debate over the pathogenesis of BAV-aortopathy. Furthermore, the lack of early detection biomarkers leads to challenges in the management of patients affected by BAV-aortopathy. Here, we critically review the current knowledge on the driving mechanisms of BAV-aortopathy together with the current clinical management and lack of available biomarkers allowing for early detection and better treatment optimization.

Characteristic impedance: frequency or time domain approach?

Objective: Characteristic impedance (Zc) is an important component in the theory of hemodynamics. It is a commonly used metric of proximal arterial stiffness and pulse wave velocity. Calculated using simultaneously measured dynamic pressure and flow data, estimates of characteristic impedance can be obtained using methods based on frequency or time domain analysis. Applications of these methods under different physiological and pathological conditions in species with different body sizes and heart rates show that the two approaches do not always agree. In this study, we have investigated the discrepancies between frequency and time domain estimates accounting for uncertainties associated with experimental processes and physiological conditions. Approach: We have used published data measured in different species including humans, dogs, and mice to investigate: (a) the effects of time delay and signal noise in the pressure-flow data, (b) uncertainties about the blood flow conditions, (c) periodicity of the cardiac cycle versus the breathing cycle, on the frequency and time domain estimates of Zc, and (d) if discrepancies observed under different hemodynamic conditions can be eliminated. Main results and Significance: We have shown that the frequency and time domain estimates are not equally sensitive to certain characteristics of hemodynamic signals including phase lag between pressure and flow, signal to noise ratio and the end of systole retrograde flow. The discrepancies between two types of estimates are inherent due to their intrinsically different mathematical expressions and therefore it is impossible to define a criterion to resolve such discrepancies. Considering the interpretation and role of Zc as an important hemodynamic parameter, we suggest that the frequency and time domain estimates should be further assessed as two different hemodynamic parameters in a future study.

Discussion on the strategy of standardized resident training model of vascular ultrasonography

Resident doctor is the beginning period of a doctor career. Resident standardization training is the basement period for the clinical ability training and is the important part for medical students after graduation education. Vascular ultrasonography belongs to ultrasound medicine and has its own discipline characteristics. The diagnosis accuracy of vascular ultrasonography largely depends on the accumulation of basic knowledge of multiple clinical sciences, standardization of operation techniques and especially the accurate application of hemodynamic theory. According to the discipline characteristics of vascular ultrasonography, we train the residents from the following five aspects: basic theory knowledge, operation techniques, clinic thinking ability, sciences research ability, communica-tion and team work ability. On the basis of practice, we explore the establishment of standardized training mode for medical professionals of vascular ultrasnography in China, training practical, innova-tive and independent talents, to provide reference for improving the professional level of vascular ultra-sound in our country. Key words: Resident doctor; Standardization training; Vascular ultrasonography; Spe-cialist ability

Three-dimensional macro-scale assessment of regional and temporal wall shear stress characteristics on aortic valve leaflets

The aortic valve (AV) achieves unidirectional blood flow between the left ventricle and the aorta. Although hemodynamic stresses have been shown to regulate valvular biology, the native wall shear stress (WSS) experienced by AV leaflets remains largely unknown. The objective of this study was to quantify computationally the macro-scale leaflet WSS environment using fluid–structure interaction modeling. An arbitrary Lagrangian–Eulerian approach was implemented to predict valvular flow and leaflet dynamics in a three-dimensional AV geometry subjected to physiologic transvalvular pressure. Local WSS characteristics were quantified in terms of temporal shear magnitude (TSM), oscillatory shear index (OSI) and temporal shear gradient (TSG). The dominant radial WSS predicted on the leaflets exhibited high amplitude and unidirectionality on the ventricularis (TSM>7.50 dyn/cm2, OSI < 0.17, TSG>325.54 dyn/cm2 s) but low amplitude and bidirectionality on the fibrosa (TSM < 2.73 dyn/cm2, OSI>0.38, TSG < 191.17 dyn/cm2 s). The radial WSS component computed in the leaflet base, belly and tip demonstrated strong regional variability (ventricularis TSM: 7.50–22.32 dyn/cm2, fibrosa TSM: 1.26–2.73 dyn/cm2). While the circumferential WSS exhibited similar spatially dependent magnitude (ventricularis TSM: 1.41–3.40 dyn/cm2, fibrosa TSM: 0.42–0.76 dyn/cm2) and side-specific amplitude (ventricularis TSG: 101.73–184.43 dyn/cm2 s, fibrosa TSG: 41.92–54.10 dyn/cm2 s), its temporal variations were consistently bidirectional (OSI>0.25). This study provides new insights into the role played by leaflet–blood flow interactions in valvular function and critical hemodynamic stress data for the assessment of the hemodynamic theory of AV disease.

A Rare Presentation of a Patient with Limb-Shaking TIA due to Severe Carotid Artery Stenosis

Background: A limb-shaking Transient Ischemic Attack (TIA) is a rare neurological symptom of hemodynamic origin caused by severe carotid artery disease. Physicians should be aware of its presence because it has a non-typical presentation and is cured by endarterectomy or stent- ing of the stenosed carotid artery. The aim of the present study was to describe a rare case of limb-shaking TIA. Description of case: A 76 year-old man with a 80% right internal carotid artery stenosis pre- sented with numerous episodes of involuntary jerky movements of his left arm and leg, associ- ated with episodes of brief weakness of the left leg, caused by preoperative optimization of his hypertension. No stroke ensued despite the daily appearance of symptoms for several months. Limb-shaking TIA was diagnosed and all symptoms disappeared immediately after an uncom- plicated carotid endarterectomy was performed. Conclusion: The clinical presentation of this limb-shaking TIA case, the first to our knowledge to appear during treatment of hypertension, supports further the hemodynamic theory of limb- shaking TIAs.

Cardiometry: new options in cardiology

Cardiometry as a new fundamental field of cardiology is described in the paper. The laws of cardiometry are identified herein. Cardiometry is based on an adequate mathematical model of hemodynamics that is described by the PoyedintsevVoronova equations. The mode of elevated blood fluidity was first described by the mathematics. This allows both to properly interpret the mechanism of the heart performance and to calculate phase-related volumes of blood in each cardiac cycle. The new interpretation of the SA and AV nodes functioning as baroreceptors is provided by the authors. A new classification for all of the varieties of ECG curve shapes has been proposed [1 - 13]. Clearly identified boundaries in each phase are provided according to the new theory of hemodynamics, and some new symbols for newly defined ECG points has been proposed. Point L which denotes the beginning of the rapid ejection phase has been introduced. The exact location of point j that is the end of the rapid ejection phase has been given by the authors [5, 13-16]. The existing ECG recording methods has been revised, and an original single-lead ECG of the ascending aorta has been developed. A rheogram is recorded in synchronism with obtaining the original single-lead ECG. Phase synchronization of the ECG and Rheo curves supplies us with a new source of data on all phase-related changes in arterial pressure. A new diagnostic device CARDIOCODE has been developed on the basis of the new theoretical basis. CARDIOCODE delivers non-invasively data on 7 phase-related volumes of blood in every cardiac cycle that was absolutely incredible in the past [1 - 11].

Etiology of bicuspid aortic valve disease: Focus on hemodynamics

The bicuspid aortic valve (BAV) is the most common form of inheritable cardiac defect. Although this abnormality may still achieve normal valvular function, it is often associated with secondary valvular and aortic complications such as calcific aortic valve disease and aortic dilation. The clinical significance and economic burden of BAV disease justify the need for improved clinical guidelines and more robust therapeutic modalities, which address the root-cause of those pathologies. Unfortunately, the etiology of BAV valvulopathy and aortopathy is still a debated issue. While the BAV anatomy and its secondary complications have been linked historically to a common genetic root, recent advances in medical imaging have demonstrated the existence of altered hemodynamics near BAV leaflets prone to calcification and BAV aortic regions vulnerable to dilation. The abnormal mechanical stresses imposed by the BAV on its leaflets and on the aortic wall could be transduced into cell-mediated processes, leading ultimately to valvular calcification and aortic medial degeneration. Despite increasing evidence for this hemodynamic etiology, the demonstration of the involvement of mechanical abnormalities in the pathogenesis of BAV disease requires the investigation of causality between the blood flow environment imposed on the leaflets and the aortic wall and the local biology, which has been lacking to date. This editorial discusses the different hypothetical etiologies of BAV disease with a particular focus on the most recent advances in cardiovascular imaging, flow characterization techniques and tissue culture methodologies that have provided new evidence in support of the hemodynamic theory.

Oral varix: a review

Ageing produces several changes on the oral cavity, and oral varix (OV) is among the most common, and they are related with some medical diseases; however, this association is not clear. The aim of this article is to offer a review of OV, regarding aetiology, clinical and histological features, associated factors, treatment and its clinical significance. Except for a higher incidence of OV in elder individuals, there is limited evidence that supports its relationship with medical conditions such us cardiovascular diseases or portal hypertension. Also, there is no consensus regarding its pathogenesis, but the hemodynamic theory embodies the most comprehensive approach. The high prevalence in elderly people stresses the need for regular oral examination, but more detailed studies regarding OV in relation to systemic diseases are needed.

Simulation of the Blood Pressure Estimation Using the Artery Compliance Model and Pulsation Waveform Model

In this study, the artery's compliance model and the pulsation waveform model was proposed to estimate blood pressure without applying HPF (High Pass Filter) on signal measured by the oscillometric method. The method proposed in the study considered two ways of estimating blood pressure. The first method of estimating blood pressure is by comparing and analyzing changes in pulsation waveform's dicrotic notch region during each cardiac period. The second method is by comparing and analyzing morphological changes in the pulsation waveform during each cardiac period, which occur in response to the change in pressure applied on the cuff. To implement these methods, we proposed the compliance model and the pulsation waveform model of the artery based on hemodynamic theory, and then conducted various simulations. The artery model presented in this study only took artery's compliance into account. Then, a pulsation waveform model was suggested, which uses characteristic changes in the pulsation waveform to estimate blood pressure. In addition, characteristic changes were observed in arterial volume by applying artery's pulsation waveform to the compliance model. The pulsation waveform model was suggested to estimate blood pressure using characteristic changes of the pulsation waveform in the arteries. This model was composed of the sum of sine waves and a Fourier's series in combination form up to 10th harmonics components of the sinusoidal waveform. Then characteristic of arterial volume change was observed by inputting pulsation waveform into the compliance model. The characteristic changes were also observed in the pulsation waveform by mapping the arterial volume change in accordance with applied cuff's pressure change to the pulsation waveform's change according to applied pressure changes by cuff. The systolic and diastolic blood pressures were estimated by applying positional change of pulsation waveform's dicrotic notch region.

Abstract 141: Bicuspid Aortic Valve Hemodynamic Abnormalities Promote Early Development of Calcific Aortic Valve Disease

INTRODUCTION: The bicuspid aortic valve (BAV) is the most common congenital cardiac anomaly and is frequently associated with calcific aortic valve disease (CAVD). Although CAVD also develops in the normal tricuspid aortic valve (TAV), its progression in the BAV is more rapid. While the accelerated calcification of BAV leaflets has been linked to genetic and atherogenic predispositions, hemodynamic abnormalities are increasingly pointed as potential pathogenic contributors. HYPOTHESIS: Supported by our previous work, which demonstrated the sensitivity of valve leaflets to the surrounding blood flow and associated wall-shear stress (WSS), we hypothesize that the abnormal WSS experienced by BAV leaflets contribute to CAVD development by promoting valvular inflammation, remodeling and osteogenic differentiation. OBJECTIVE: This study aims at comparing ex vivo the effects of TAV and BAV leaflet WSS on valvular pathogenesis. METHODS: The native, side-specific WSS experienced by TAV and type-I (i.e., fused and non-coronary) BAV leaflets were obtained computationally using fluid-structure interaction simulations. Fresh porcine leaflets were subjected for 48 hours to each of the three WSS conditions using a novel double-sided shear stress bioreactor. Tissue response was characterized via Western blot and immunohistochemistry in terms of markers of endothelial activation (VCAM-1, ICAM-1), paracrine expression (BMP-4), TGF-β/Wnt signaling pathways (TGF-β1, β-catenin), extracellular matrix remodeling (cathepsin L, MMP-2, MMP-9) and osteogenic differentiation (α-SMA, osteocalcin). RESULTS: No significant differences in VCAM-1 and ICAM-1 expressions were detected between tissue exposed to TAV and BAV WSS. While the native WSS experienced by the TAV and non-coronary BAV leaflets maintained tissue homeostasis, tissue exposure to the fused BAV leaflet WSS resulted in a significant pathological response marked by the upregulations of BMP-4, β-catenin, MMP-2 and osteocalcin expressions. CONCLUSION: This study demonstrates the pathological nature of the native BAV hemodynamics and confirms the higher susceptibility of the fused BAV leaflet to calcify. The results provide new insights into the hemodynamic theory of BAV calcification.