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      Modeling arterial pulse waves in healthy aging: a database for in silico evaluation of hemodynamics and pulse wave indexes

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          Abstract

          The arterial pulse wave (PW) is a rich source of information on cardiovascular (CV) health. It is widely measured by both consumer and clinical devices. However, the physical determinants of the PW are not yet fully understood, and the development of PW analysis algorithms is limited by a lack of PW data sets containing reference CV measurements. Our aim was to create a database of PWs simulated by a computer to span a range of CV conditions, representative of a sample of healthy adults. The typical CV properties of 25–75 yr olds were identified through a literature review. These were used as inputs to a computational model to simulate PWs for subjects of each age decade. Pressure, flow velocity, luminal area, and photoplethysmographic PWs were simulated at common measurement sites, and PW indexes were extracted. The database, containing PWs from 4,374 virtual subjects, was verified by comparing the simulated PWs and derived indexes with corresponding in vivo data. Good agreement was observed, with well-reproduced age-related changes in hemodynamic parameters and PW morphology. The utility of the database was demonstrated through case studies providing novel hemodynamic insights, in silico assessment of PW algorithms, and pilot data to inform the design of clinical PW algorithm assessments. In conclusion, the publicly available PW database is a valuable resource for understanding CV determinants of PWs and for the development and preclinical assessment of PW analysis algorithms. It is particularly useful because the exact CV properties that generated each PW are known.

          NEW & NOTEWORTHY First, a comprehensive literature review of changes in cardiovascular properties with age was performed. Second, an approach for simulating pulse waves (PWs) at different ages was designed and verified against in vivo data. Third, a PW database was created, and its utility was illustrated through three case studies investigating the determinants of PW indexes. Fourth, the database and tools for creating the database, analyzing PWs, and replicating the case studies are freely available.

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          Mechanical factors in arterial aging: a clinical perspective.

          The human arterial system in youth is beautifully designed for its role of receiving spurts of blood from the left ventricle and distributing this as steady flow through peripheral capillaries. Central to such design is "tuning" of the heart to arterial tree; this minimizes aortic pressure fluctuations and confines flow pulsations to the larger arteries. With aging, repetitive pulsations (some 30 million/year) cause fatigue and fracture of elastin lamellae of central arteries, causing them to stiffen (and dilate), so that reflections return earlier to the heart; in consequence, aortic systolic pressure rises, diastolic pressure falls, and pulsations of flow extend further into smaller vessels of vasodilated organs (notably the brain and kidney). Stiffening leads to increased left ventricular (LV) load with hypertrophy, decreased capacity for myocardial perfusion, and increased stresses on small arterial vessels, particularly of brain and kidney. Clinical manifestations are a result of diastolic LV dysfunction with dyspnea, predisposition to angina, and heart failure, and small vessel degeneration in brain and kidney with intellectual deterioration and renal failure. While aortic stiffening is the principal cause of cardiovascular disease with age in persons who escape atherosclerotic complications, it is not a specific target for therapy. The principal target is the smooth muscle in distributing arteries, whose relaxation has little effect on peripheral resistance but causes substantial reduction in the magnitude of wave reflection. Such relaxation is achieved through regular exercise and with the vasodilating drugs that are used in modern treatment of hypertension and cardiac failure.
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            Reference ranges for cardiac structure and function using cardiovascular magnetic resonance (CMR) in Caucasians from the UK Biobank population cohort

            Background Cardiovascular magnetic resonance (CMR) is the gold standard method for the assessment of cardiac structure and function. Reference ranges permit differentiation between normal and pathological states. To date, this study is the largest to provide CMR specific reference ranges for left ventricular, right ventricular, left atrial and right atrial structure and function derived from truly healthy Caucasian adults aged 45–74. Methods Five thousand sixty-five UK Biobank participants underwent CMR using steady-state free precession imaging at 1.5 Tesla. Manual analysis was performed for all four cardiac chambers. Participants with non-Caucasian ethnicity, known cardiovascular disease and other conditions known to affect cardiac chamber size and function were excluded. Remaining participants formed the healthy reference cohort; reference ranges were calculated and were stratified by gender and age (45–54, 55–64, 65–74). Results After applying exclusion criteria, 804 (16.2%) participants were available for analysis. Left ventricular (LV) volumes were larger in males compared to females for absolute and indexed values. With advancing age, LV volumes were mostly smaller in both sexes. LV ejection fraction was significantly greater in females compared to males (mean ± standard deviation [SD] of 61 ± 5% vs 58 ± 5%) and remained static with age for both genders. In older age groups, LV mass was lower in men, but remained virtually unchanged in women. LV mass was significantly higher in males compared to females (mean ± SD of 53 ± 9 g/m2 vs 42 ± 7 g/m2). Right ventricular (RV) volumes were significantly larger in males compared to females for absolute and indexed values and were smaller with advancing age. RV ejection fraction was higher with increasing age in females only. Left atrial (LA) maximal volume and stroke volume were significantly larger in males compared to females for absolute values but not for indexed values. LA ejection fraction was similar for both sexes. Right atrial (RA) maximal volume was significantly larger in males for both absolute and indexed values, while RA ejection fraction was significantly higher in females. Conclusions We describe age- and sex-specific reference ranges for the left ventricle, right ventricle and atria in the largest validated normal Caucasian population. Electronic supplementary material The online version of this article (doi:10.1186/s12968-017-0327-9) contains supplementary material, which is available to authorized users.
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              Prospective evaluation of a method for estimating ascending aortic pressure from the radial artery pressure waveform.

              Pressure wave reflection in the upper limb causes amplification of the arterial pulse so that radial systolic and pulse pressures are greater than in the ascending aorta. Wave transmission properties in the upper limbs (in contrast to the descending aorta and lower limbs) change little with age, disease, and drug therapy in adult humans. Such consistency has led to use of a generalized transfer function to synthesize the ascending aortic pressure pulse from the radial pulse. Validity of this approach was tested for estimation of aortic systolic, diastolic, pulse, and mean pressures from the radial pressure waveform. Ascending aortic and radial pressure waveforms were recorded simultaneously at cardiac surgery, before initiation of cardiopulmonary bypass, with matched, fluid-filled manometer systems in 62 patients under control conditions and during nitroglycerin infusion. Aortic pressure pulse waves, generated from the radial pulse, showed agreement with the measured aortic pulse waves with respect to systolic, diastolic, pulse, and mean pressures, with mean differences <1 mm Hg. Control differences in Bland-Altman plots for mean+/-SD in mm Hg were systolic, 0.0+/-4.4; diastolic, 0.6+/-1.7; pulse, -0.7+/-4.2; and mean pressure, -0.5+/-2.0. For nitroglycerin infusion, differences respectively were systolic, -0.2+/-4.3; diastolic, 0.6+/-1.7; pulse, -0.8+/-4.1; and mean pressure, -0.4+/-1.8. Differences were within specified limits of the Association for the Advancement of Medical Instrumentation SP10 criteria. In contrast, differences between recorded radial and aortic systolic and pulse pressures were well outside the criteria (respectively, 15.7+/-8.4 and 16.3+/-8.5 for control and 14.5+/-7.3 and 15.1+/-7.3 mm Hg for nitroglycerin). Use of a generalized transfer function to synthesize radial artery pressure waveforms can provide substantially equivalent values of aortic systolic, pulse, mean, and diastolic pressures.
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                Author and article information

                Journal
                Am J Physiol Heart Circ Physiol
                Am. J. Physiol. Heart Circ. Physiol
                ajpheart
                Am J Physiol Heart Circ Physiol
                AJPHEART
                American Journal of Physiology - Heart and Circulatory Physiology
                American Physiological Society (Bethesda, MD )
                0363-6135
                1522-1539
                1 November 2019
                23 August 2019
                23 August 2019
                : 317
                : 5
                : H1062-H1085
                Affiliations
                [1] 1Department of Biomedical Engineering, School of Biomedical Engineering and Imaging Sciences, King’s College London, King’s Health Partners, London, United Kingdom
                [2] 2Department of Clinical Pharmacology, King’s College London, King’s Health Partners, London, United Kingdom
                [3] 3Institute of Personalized Medicine, Sechenov University , Moscow, Russia
                Author notes
                Address for reprint requests and other correspondence: P. H. Charlton, Dept. of Biomedical Engineering, 4th Fl. Lambeth Wing, St. Thomas’ Hospital, Westminster Bridge Rd., London, SE1 7EH, UK (e-mail: peter.charlton@ 123456kcl.ac.uk ).
                Author information
                https://orcid.org/0000-0003-3836-8655
                https://orcid.org/0000-0003-1507-8380
                https://orcid.org/0000-0003-3742-5259
                Article
                H-00218-2019 H-00218-2019
                10.1152/ajpheart.00218.2019
                6879924
                31442381
                f383dfcc-6de9-49d2-b177-fc0a50b8afc2
                Copyright © 2019 the American Physiological Society

                Licensed under Creative Commons Attribution CC-BY 4.0: © the American Physiological Society.

                History
                : 12 April 2019
                : 9 July 2019
                : 28 July 2019
                Funding
                Funded by: British Heart Foundation (BHF) 10.13039/501100000274
                Award ID: PG/15/104/31913
                Funded by: Wellcome Trust 10.13039/100004440
                Award ID: WT 203148/Z/16/Z
                Funded by: Engineering and Physical Sciences Research Council (EPSRC) 10.13039/501100000266
                Award ID: WT 203148/Z/16/Z
                Categories
                Research Article
                Vascular Biology and Microcirculation

                Cardiovascular Medicine
                aging,arteries,blood flow,database of virtual subjects,pulse wave
                Cardiovascular Medicine
                aging, arteries, blood flow, database of virtual subjects, pulse wave

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