Aging is associated with an earlier arrival of reflected waves without a distal shift in reflection sites

Background-Despite pronounced increases in central pulse wave velocity (PWV) with aging, reflected wave transit time (RWTT), traditionally defined as the timing of the inflection point (T-INF) in the central pressure waveform, does not appreciably decrease, leading to the controversial proposition of a "distal-shift" of reflection sites. T-INF, however, is exceptionally prone to measurement error and is also affected by ejection pattern and not only by wave reflection. We assessed whether RWTT, assessed by advanced pressure-flow analysis, demonstrates the expected decline with aging. Methods and Results-We studied a sample of unselected adults without cardiovascular disease (n=48; median age 48 years) and a clinical population of older adults with suspected/established cardiovascular disease (n=164; 61 years). We measured central pressure and flow with carotid tonometry and phase-contrast MRI, respectively. We assessed RWTT using wave-separation analysis (RWTTWSA) and partially distributed tube-load (TL) modeling (RWTTTL). Consistent with previous reports, T-INF did not appreciably decrease with age despite pronounced increases in PWV in both populations. However, aging was associated with pronounced decreases in RWTTWSA (general population -15.0 ms/decade, P<0.001; clinical population -9.07 ms/decade, P=0.003) and RWTTTL (general -15.8 ms/decade, P<0.001; clinical -11.8 ms/decade, P<0.001). There was no evidence of an increased effective reflecting distance by either method. TINF was shown to reliably represent RWTT only under highly unrealistic assumptions about input impedance. Conclusions-RWTT declines with age in parallel with increased PWV, with earlier effects of wave reflections and without a distal shift in reflecting sites. These findings have important implications for our understanding of the role of wave reflections with aging

Cardiovascular instrumentation for spaceflight

The observation mechanisms dealing with pressure, flow, morphology, temperature, etc. are discussed. The approach taken in the performance of this study was to (1) review ground and space-flight data on cardiovascular function, including earlier related ground-based and space-flight animal studies, Mercury, Gemini, Apollo, Skylab, and recent bed-rest studies, (2) review cardiovascular measurement parameters required to assess individual performance and physiological alternations during space flight, (3) perform an instrumentation survey including a literature search as well as personal contact with the applicable investigators, (4) assess instrumentation applicability with respect to the established criteria, and (5) recommend future research and development activity. It is concluded that, for the most part, the required instrumentation technology is available but that mission-peculiar criteria will require modifications to adapt the applicable instrumentation to a space-flight configuration

The Noninvasive Measurement of Central Aortic Blood Pressure Waveform

Central aortic pressure (CAP) is a potential surrogate of brachial blood pressure in both clinical practice and routine health screening. It directly reflects the status of the central aorta. Noninvasive measurement of CAP becomes a crucial technique of great interest. There have been advances in recent years, including the proposal of novel methods and commercialization of several instruments. This chapter briefly introduces the clinical importance of CAP and the theoretical basis for the generation of CAP in the first and second sections. The third section describes and discusses the measurement of peripheral blood pressure waveforms, which is employed to estimate CAP. We then review the proposed methods for the measurement of CAP. The calibration of blood pressure waveforms is discussed in the fourth section. After a brief discussion of the technical limitations, we give suggestions for perspectives and future challenges

Development, Validation, and Clinical Application of a Numerical Model for Pulse Wave Velocity Propagation in a Cardiovascular System with Application to Noninvasive Blood Pressure Measurements

High blood pressure blood pressure is an important risk factor for cardiovascular disease and affects almost one-third of the U.S. adult population. Historical cuff-less non-invasive techniques used to monitor blood pressure are not accurate and highlight the need for first principal models. The first model is a one-dimensional model for pulse wave velocity (PWV) propagation in compliant arteries that accounts for nonlinear fluids in a linear elastic thin walled vessel. The results indicate an inverse quadratic relationship (R^2=.99) between ejection time and PWV, with ejection time dominating the PWV shifts (12%). The second model predicts the general relationship between PWV and blood pressure with a rigorous account of nonlinearities in the fluid dynamics, blood vessel elasticity, and finite dynamic deformation of a membrane type thin anisotropic wall. The nonlinear model achieves the best match with the experimental data. To retrieve individual vascular information of a patient, the inverse problem of hemodynamics is presented, calculating local orthotropic hyperelastic properties of the arterial wall. The final model examines the impact of the thick arterial wall with different material properties in the radial direction. For a hypertensive subject the thick wall model provides improved accuracy up to 8.4% in PWV prediction over its thin wall counterpart. This translates to nearly 20% improvement in blood pressure prediction based on a PWV measure. The models highlight flow velocity is additive to the classic pressure wave, suggesting flow velocity correction may be important for cuff-less, non-invasive blood pressure measures. Systolic flow correction of the measured PWV improves the R2 correlation to systolic blood pressure from 0.81 to 0.92 for the mongrel dog study, and 0.34 to 0.88 for the human subjects study. The algorithms and insight resulting from this work can enable the development of an integrated microsystem for cuff-less, non-invasive blood pressure monitoring

Methods and Algorithms for Cardiovascular Hemodynamics with Applications to Noninvasive Monitoring of Proximal Blood Pressure and Cardiac Output Using Pulse Transit Time

Advanced health monitoring and diagnostics technology are essential to reduce the unrivaled number of human fatalities due to cardiovascular diseases (CVDs). Traditionally, gold standard CVD diagnosis involves direct measurements of the aortic blood pressure (central BP) and flow by cardiac catheterization, which can lead to certain complications. Understanding the inner-workings of the cardiovascular system through patient-specific cardiovascular modeling can provide new means to CVD diagnosis and relating treatment. BP and flow waves propagate back and forth from heart to the peripheral sites, while carrying information about the properties of the arterial network. Their speed of propagation, magnitude and shape are directly related to the properties of blood and arterial vasculature. Obtaining functional and anatomical information about the arteries through clinical measurements and medical imaging, the digital twin of the arterial network of interest can be generated. The latter enables prediction of BP and flow waveforms along this network. Point of care devices (POCDs) can now conduct in-home measurements of cardiovascular signals, such as electrocardiogram (ECG), photoplethysmogram (PPG), ballistocardiogram (BCG) and even direct measurements of the pulse transit time (PTT). This vital information provides new opportunities for designing accurate patient-specific computational models eliminating, in many cases, the need for invasive measurements. One of the main efforts in this area is the development of noninvasive cuffless BP measurement using patient’s PTT. Commonly, BP prediction is carried out with regression models assuming direct or indirect relationships between BP and PTT. However, accounting for the nonlinear FSI mechanics of the arteries and the cardiac output is indispensable. In this work, a monotonicity-preserving quasi-1D FSI modeling platform is developed, capable of capturing the hyper-viscoelastic vessel wall deformation and nonlinear blood flow dynamics in arbitrary arterial networks. Special attention has been dedicated to the correct modeling of discontinuities, such as mechanical properties mismatch associated with the stent insertion, and the intertwining dynamics of multiscale 3D and 1D models when simulating the arterial network with an aneurysm. The developed platform, titled Cardiovascular Flow ANalysis (CardioFAN), is validated against well-known numerical, in vitro and in vivo arterial network measurements showing average prediction errors of 5.2%, 2.8% and 1.6% for blood flow, lumen cross-sectional area, and BP, respectively. CardioFAN evaluates the local PTT, which enables patient-specific calibration and its application to input signal reconstruction. The calibration is performed based on BP, stroke volume and PTT measured by POCDs. The calibrated model is then used in conjunction with noninvasively measured peripheral BP and PTT to inversely restore the cardiac output, proximal BP and aortic deformation in human subjects. The reconstructed results show average RMSEs of 1.4% for systolic and 4.6% for diastolic BPs, as well as 8.4% for cardiac output. This work is the first successful attempt in implementation of deterministic cardiovascular models as add-ons to wearable and smart POCD results, enabling continuous noninvasive monitoring of cardiovascular health to facilitate CVD diagnosis

Non-invasive evaluation of left ventricular afterload, part 2 : arterial pressure-flow and pressure-volume relations in humans

The mechanical load imposed by the systemic circulation to the left ventricle is an important determinant of normal and abnormal cardiovascular function. Left ventricular afterload is determined by complex time-varying phenomena, which affect pressure and flow patterns generated by the pumping ventricle. Left ventricular afterload is best described in terms of pressure-flow relations, allowing for quantification of various components of load using simplified biomechanical models of the circulation, with great potential for mechanistic understanding of the role of central hemodynamics in cardiovascular disease and the effects of therapeutic interventions. In the second part of this tutorial, we review analytic methods used to characterize left ventricular afterload, including analyses of central arterial pressure-flow relations and windkessel modeling (pressure-volume relations). Conceptual descriptions of various models and methods are emphasized over mathematical ones. Our review is aimed at helping researchers and clinicians obtain and interpret results from analyses of left ventricular afterload in clinical and epidemiological settings

Noninvasive cardiac output and central systolic pressure from cuff-pressure and pulse wave velocity

Goal: We introduce a novel approach to estimate cardiac output (CO) and central systolic blood pressure (cSBP) from noninvasive measurements of peripheral cuff-pressure and carotid-to-femoral pulse wave velocity (cf-PWV). Methods: The adjustment of a previously validated one-dimensional arterial tree model is achieved via an optimization process. In the optimization loop, compliance and resistance of the generic arterial tree model as well as aortic flow are adjusted so that simulated brachial systolic and diastolic pressures and cf-PWV converge towards the measured brachial systolic and diastolic pressures and cf-PWV. The process is repeated until full convergence in terms of both brachial pressures and cf-PWV is reached. To assess the accuracy of the proposed framework, we implemented the algorithm on in vivo anonymized data from 20 subjects and compared the method-derived estimates of CO and cSBP to patient-specific measurements obtained with Mobil-O-Graph apparatus (central pressure) and two-dimensional transthoracic echocardiography (aortic blood flow). Results: Both CO and cSBP estimates were found to be in good agreement with the reference values achieving an RMSE of 0.36 L/min and 2.46 mmHg, respectively. Low biases were reported, namely -0.04 +/- 0.36 L/min for CO predictions and -0.27 +/- 2.51 mmHg for cSBP predictions. Significance: Our one-dimensional model can be successfully "tuned" to partially patient-specific standards by using noninvasive, easily obtained peripheral measurement data. The in vivo evaluation demonstrated that this method can potentially be used to obtain central aortic hemodynamic parameters in a noninvasive and accurate way

Arterial Stiffness in the Young: Assessment, Determinants, and Implications

Arterial stiffness describes the rigidity of the arterial wall. Its significance owes to its relationship with the pulsatile afterload presented to the left ventricle and its implications on ventricular-arterial coupling. In adults, the contention that arterial stiffness as a marker and risk factor for cardiovascular morbidity and mortality is gaining support. Noninvasive methods have increasingly been adopted in both the research and clinical arena to determine local, segmental, and systemic arterial stiffness in the young. With adoption of these noninvasive techniques for use in children and adolescents, the phenomenon and significance of arterial stiffening in the young is beginning to be unveiled. The list of childhood factors and conditions found to be associated with arterial stiffening has expanded rapidly over the last decade; these include traditional cardiovascular risk factors, prenatal growth restriction, vasculitides, vasculopathies associated with various syndromes, congenital heart disease, and several systemic diseases. The findings of arterial stiffening have functional implications on energetic efficiency, structure, and function of the left ventricle. Early identification of arterial dysfunction in childhood may provide a window for early intervention, although longitudinal studies are required to determine whether improvement of arterial function in normal and at-risk paediatric populations will be translated into clinical benefits

An optimization study of estimating blood pressure models based on pulse arrival time for continuous monitoring

Continuous blood pressure (BP) monitoring has a significant meaning for the prevention and early diagnosis of cardiovascular disease. However, under different calibration methods, it is difficult to determine which model is better for estimating BP. This study was firstly designed to reveal a better BP estimation model by evaluating and optimizing different BP models under a justified and uniform criterion, i.e., the advanced point-to-point pairing method (PTP). Here, the physical trial in this study caused the BP increase largely. In addition, the PPG and ECG signals were collected while the cuff bps were measured for each subject. The validation was conducted on four popular vascular elasticity (VE) models (MK-EE, L-MK, MK-BH, and dMK-BH) and one representative elastic tube (ET) model, i.e., M-M. The results revealed that the VE models except for L-MK outperformed the ET model. The linear L-MK as a VE model had the largest estimated error, and the nonlinear M-M model had a weaker correlation between the estimated BP and the cuff BP than MK-EE, MK-BH, and dMK-BH models. Further, in contrast to L-MK, the dMK-BH model had the strongest correlation and the smallest difference between the estimated BP and the cuff BP including systolic blood pressure (SBP) and diastolic blood pressure (DBP) than others. In this study, the simple MK-EE model showed the best similarity to the dMK-BH model. There were no significant changes between MK-EE and dMK-BH models. These findings indicated that the nonlinear MK-EE model with low estimated error and simple mathematical expression was a good choice for application in wearable sensor devices for cuff-less BP monitoring compared to others

Short-Term Repeatability of Noninvasive Aortic Pulse Wave Velocity Assessment: Comparison between Methods and Devices

BACKGROUND Aortic pulse wave velocity (PWV) is an indirect index of arterial stiffness and an independent cardiovascular risk factor. Consistency of PWV assessment over time is thus an essential feature for its clinical application. However, studies providing a comparative estimate of the reproducibility of PWV across different noninvasive devices are lacking, especially in the elderly and in individuals at high cardiovascular risk. METHODS Aimed at filling this gap, short-term repeatability of PWV, estimated with 6 different devices (Complior Analyse, PulsePen-ETT, PulsePen-ET, SphygmoCor Px/Vx, BPLab, and Mobil-O-Graph), was evaluated in 102 high cardiovascular risk patients hospitalized for suspected coronary artery disease (72 males, 65 ± 13 years). PWV was measured in a single session twice, at 15-minute interval, and its reproducibility was assessed though coefficient of variation (CV), coefficient of repeatability, and intraclass correlation coefficient. RESULTS The CV of PWV, measured with any of these devices, was <10%. Repeatability was higher with cuff-based methods (BPLab: CV = 5.5% and Mobil-O-Graph: CV = 3.4%) than with devices measuring carotid-femoral PWV (Complior: CV = 8.2%; PulsePen-TT: CV = 8.0%; PulsePen-ETT: CV = 5.8%; and SphygmoCor: CV = 9.5%). In the latter group, PWV repeatability was lower in subjects with higher carotid-femoral PWV. The differences in PWV between repeated measurements, except for the Mobil-O-Graph, did not depend on short-term variations of mean blood pressure or heart rate. CONCLUSIONS Our study shows that the short-term repeatability of PWV measures is good but not homogenous across different devices and at different PWV values. These findings, obtained in patients at high cardiovascular risk, may be relevant when evaluating the prognostic importance of PW