Clinical Non-Invasive Hemodynamics Core Facility

Debra I. Diz, PhD, Hossam Shaltout, PhD

The HVRC has a Clinical Research component consisting of an outpatient facility located in the Janeway Clinical Sciences building, staffed with a receptionist, exam rooms and a hemodynamics laboratory that is equipped with diagnostic tests for vascular compliance, central pressures, indices of autonomic function including continuous non-invasive blood pressure monitoring system and software for spectral and sequence evaluation of sympathetic and vagal contributions to blood pressure and heart rate, and 24-hour ambulatory blood pressure monitoring. We provide these services for both clinical testing and clinical research studies.

Our non-invasive testing capabilities include a variety of measures of vascular and autonomic function. The descriptions below highlight the main purpose of each test and citations for their use in the clinical setting are provided. Tests are available for both research studies and clinical patient diagnosis and management. Drs. Diz and Shaltout currently oversee this facility and work with investigators to coordinate access to all equipment needed for various studies. A complete list of the measured variables for each test is available by contacting Dr. Hossam Shaltout at:

Noninvasive Assessment of Vascular Function: as published by Smith 1

  • BioZ by CardioDynamics, San Diego, CA
  • Collins VP-2000 by Wave Nexus Corp., San Antonio, TX
  • HDI CR-2000 by Hypertension Diagnostics Inc., Egan, MN
  • SphygmoCor by AtCor Medical, Lisle, IL

Electrical impedance cardiography (ICG), the BioZ®, Model BZ 4110-101D, by Cardio Dynamics, San Diego, CA

This technique relies upon the minute current transmitted across the thorax by ICG seeking its path of least resistance. The impedance changes of the blood flow through the aortic arch are measured on a beat by beat sequence from which the stroke volume (SV), cardiac output (CO), systemic vascular resistance (SVR), thoracic fluid volume (TFC), and other hemodynamic variables are calculated. This is a simple procedure that allows the recording of twelve hemodynamic variables within minutes. Validity and reproducibility of the procedure has been established 2, 3. Applicable software is used to calculate cardiac output and systemic vascular resistance. Whereas the majority of clinical application and publication were related to cardiology, particularly congestive heart failure 4, clinical relevance to the treatment of hypertension is now apparent 5.

The SphygomoCor PX Pulse Wave Analysis System (Model SCOR-PX), by AtCor Medical, Lisle, IL

This device estimates the ascending aortic blood pressure wave by applanation tonometry and its specific transfer function. A pressure transducer records the pressure waveform from the radial or carotid artery and calculates the central aortic hemodynamic indices that have clinical use 6, 7. The accuracy for this transfer function to measure central aortic pressure and the augmentation and augmentation index of the pulse wave has been well validated 5, 8-11.

HDI/Pulse Wave CR-2000, Hypertension Diagnostics Inc, Eagan, MN

The HDI also utilizes applanation tonometry evaluation of the pulse wave form. However, it evaluates the diastolic portion of the wave form utilizing a modified Windkessel equation to derive its functions. Using an empirical formula derived from a multivariate analysis of subjects with normal heart function an estimate of the stroke volume and cardiac output are made. Validation and reliability of repetitive measurements has been accomplished 12, 13. Systemic vascular resistance and total vascular impedance are computed. Two other vascular compliance indices, generally not available from other devices, are derived by special equations. These are large artery and small artery elasticity indices, C1 and C2, stated to represent large arterial capacitive compliance and oscillatory arterial compliance, respectively 14.

Colin VP-2000/1000 Vascular Profiling System by Colin Corporation, San Antonio, TX

The significance of the pulse wave velocity has been recognized for nearly a century15. Arterial pulse wave velocity is measured simultaneously and bilaterally by the Colin system. Using its unique multihead pressure transducers PWV for carotid-heart, carotid-femoral (cf), brachial-heart, heart-femoral, femoral-ankle, and brachial-ankle (ba) are recorded and EKG-gated to a single heart beat. This device is possibly the easiest to utilize as it requires only the placing of the four blood pressure cuffs, each with its own transducer. All of the PWV data is then available in a minute. The blood pressure, a short lead II EKG tracing, each of the site pulse waves, the ankle/brachial index (ABI) and the carotid augmentation index are recorded simultaneously. Validity and reproducibility have been established 16-21.

Ambulatory Blood Pressure Monitoring, ABPM. SpaceLabs Medical, Model 90207, Issaquah, WA

Standard 24 hour monitoring certainly is the most readily available and commonly used device. It records sleeping and active blood pressures, blood pressure variance, and nocturnal changes. The accuracy of the ambulatory readings has been verified 22. Criteria have been established for appropriate interpretation using the values of <130/80 mmHg for day time and <120/70 mmHg for night time readings. Spacelabs Medical is validated by the U.S. Association for Advancement of Medical Instrumentation for clinical ambulatory blood pressure measurement.

Determination of Baroreflex Sensitivity (BRS) for Control of Heart Rate, Heart Rate Variability (HRV) and Blood Pressure Variability (BPV) using Spectral Analysis Software, Nevrokard, Medistar, Ljubljana, Slovenia

Continuous blood pressure, heart rate are acquired from noninvasive finger arterial pressure measurement via CNAP- Biopac system in addition to ECG for a minimum of 5 minutes. Systolic arterial pressure (SAP) and RR intervals (RRI) files generated via the data acquisition system  (BIOPAC acquisition software, Santa Barbara, CA) at 1000 HZ are analyzed using Nevrokard BRSsoftware (Nevrokard BRS, Medistar, Ljubljana, Slovenia) to obtain measures of BRS, HRV and BPV through frequency and sequence methods.

Time-Domain Analysis:  Three time-domain parameters are used to measure hemodynamic variability as in previous studies 26, 27. Heart rate variability determined by computing the standard deviation of beat-to-beat interval (SDRR) and the root mean square of successive beat-to-beat differences in R-R interval duration (rMSSD). The standard deviation of the mean arterial pressure (SDMAP) will be used as a measure for blood pressure variability.

Nevrokard BRS software has been validated in rats28, sheep29 and humans30


1.  Smith RD, Levy PJ. New Techniques for Assessment of Vascular Function. Therapeutic Advances in Cardiovascular Disease. 2008.
2.  Greenberg BH, Hermann DD, Pranulis MF, Lazio L, Cloutier D. Reproducibility of impedance cardiography hemodynamic measures in clinically stable heart failure patients. Congest Heart Fail. 2000;6:74-80.
3.   Belardinelli R, Ciampani N, Costantini C, Blandini A, Purcaro A. Comparison of impedance cardiography with thermodilution and direct Fick methods for noninvasive measurement of stroke volume and cardiac output during incremental exercise in patients with ischemic cardiomyopathy. Am J Cardiol. 1996;77:1293-1301.
4.   Drazner MH, Thompson B, Rosenberg PB, Kaiser PA, Boehrer JD, Baldwin BJ, Dries DL, Yancy CW. Comparison of impedance cardiography with invasive hemodynamic measurements in patients with heart failure secondary to ischemic or nonischemic cardiomyopathy. Am J Cardiol. 2002;89:993-995.
5.    Karamanoglu M, O'Rourke MF, Avolio AP, Kelly RP. An analysis of the relationship between central aortic and peripheral upper limb pressure waves in man. Eur Heart J. 1993;14:160-167.
6.    Kelly R, Hayward C, Winter D, Avolio A, Orourke M. Non-Invasive Registration of the Arterial-Pressure Pulse Waveform Using High-Fidelity Applanation Tonometry. Australian and New Zealand Journal of Medicine. 1988;18:374-374.
7.    Drzewiecki GM, Melbin J, Noordergraaf A. Arterial tonometry: review and analysis. J Biomech. 1983;16:141-152.
8.    Pauca AL, O'Rourke MF, Kon ND. Prospective evaluation of a method for estimating ascending aortic pressure from the radial artery pressure waveform. Hypertension. 2001;38:932-937.
9.    Fetics B, Nevo E, Chen CH, Kass DA. Parametric model derivation of transfer function for noninvasive estimation of aortic pressure by radial tonometry. IEEE Trans Biomed Eng. 1999;46:698-706.
10.  Chen CH, Nevo E, Fetics B, Pak PH, Yin FC, Maughan WL, Kass DA. Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure. Validation of generalized transfer function. Circulation. 1997;95:1827-1836.
11.   Smulyan H, Siddiqui DS, Carlson RJ, London GM, Safar ME. Clinical utility of aortic pulses and pressures calculated from applanated radial-artery pulses. Hypertension. 2003;42:150-155.
12.   Cohn JN, Finkelstein S, McVeigh G, Morgan D, LeMay L, Robinson J, Mock J. Noninvasive pulse wave analysis for the early detection of vascular disease. Hypertension. 1995;26:503-508.
13.   Zimlichman R, Shargorodsky M, Boaz M, Duprez D, Rahn KH, Rizzoni D, Payeras AC, Hamm C, McVeigh G. Determination of arterial compliance using blood pressure waveform analysis with the CR-2000 system: Reliability, repeatability, and establishment of normal values for healthy European population--the seven European sites study (SESS). Am J Hypertens. 2005;18:65-71.
14.   Abdelhamed AI, Levy P, SigmonSmith K, Barnes R, Smith R, Ferrario CM. Comparison of two non-invasive methods for office-based hemodynamic measurements. 2002;15:90A.
15.   Bramwell JC, Hill AV. The Velocity of the Pulse Wave in Man. Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character.93:298-306 CR  - Copyright &#169; 1922 The Royal Society.
16.   McVeigh GE, Bratteli CW, Morgan DJ, Alinder CM, Glasser SP, Finkelstein SM, Cohn JN. Age-related abnormalities in arterial compliance identified by pressure pulse contour analysis: aging and arterial compliance. Hypertension. 1999;33:1392-1398.
17.   Yambe M, Tomiyama H, Yamada J, Koji Y, Motobe K, Shiina K, Yamamoto Y, Yamashina A. Arterial stiffness and progression to hypertension in Japanese male subjects with high normal blood pressure. J Hypertens. 2007;25:87-93.
18.   Tomiyama H, Hashimoto H, Hirayama Y, Yambe M, Yamada J, Koji Y, Shiina K, Yamamoto Y, Yamashina A. Synergistic acceleration of arterial stiffening in the presence of raised blood pressure and raised plasma glucose. Hypertension. 2006;47:180-188.
19.   Tomiyama H, Arai T, Koji Y, Yambe M, Motobe K, Zaydun G, Yamamoto Y, Hori S, Yamashina A. The age-related increase in arterial stiffness is augmented in phases according to the severity of hypertension. Hypertens Res. 2004;27:465-470.
20.   Motobe K, Tomiyama H, Koji Y, Yambe M, Gulinisa Z, Arai T, Ichihashi H, Nagae T, Ishimaru S, Yamashina A. Cut-off value of the ankle-brachial pressure index at which the accuracy of brachial-ankle pulse wave velocity measurement is diminished. Circ J. 2005;69:55-60.
21.   Yamashina A, Tomiyama H, Arai T, Koji Y, Yambe M, Motobe H, Glunizia Z, Yamamoto Y, Hori S. Nomogram of the relation of brachial-ankle pulse wave velocity with blood pressure. Hypertens Res. 2003;26:801-806.
22.   O'Brien E, Mee F, Atkins N, O'Malley K. Accuracy of the SpaceLabs 90207 determined by the British Hypertension Society Protoco. Paper presented at: Journal of Hypertension, 1991.
23.    Parati G, Frattola A, Di Rienzo M, Castiglioni P, Pedotti A, Mancia G. Effects of aging on 24-h dynamic baroreceptor control of heart rate in ambulant subjects. Am J Physiol. 1995;268:H1606-1612.
24.    Laitinen T, Hartikainen J, Niskanen L, Geelen G, Lansimies E. Sympathovagal balance is major determinant of short-term blood pressure variability in healthy subjects. Am J Physiol. 1999;276:H1245-1252.
25.    Wang YP, Cheng YJ, Huang CL. Spontaneous baroreflex measurement in the assessment of cardiac vagal control. Clin Auton Res. 2004;14:189-193.
26.     Sgoifo A, de Boer SF, Westenbroek C, Maes FW, Beldhuis H, Suzuki T, Koolhaas JM. Incidence of arrhythmias and heart rate variability in wild-type rats exposed to social stress. Am J Physiol. 1997;273:H1754-1760.
27.     Stein PK, Bosner MS, Kleiger RE, Conger BM. Heart rate variability: a measure of cardiac autonomic tone. Am Heart J. 1994;127:1376-1381.
28.     Shaltout HA, Abdel-Rahman AA. Mechanism of fatty acids induced suppression of cardiovascular reflexes in rats. J Pharmacol Exp Ther. 2005;314:1328-1337.
29.    Shaltout HA, Figueroa JP, Rose JC, Chappell MC, Diz DI, Averill DB. Antenatal betamethasone causes angiotensin II-mediated impairment of baroreflex control of heart rate. Journal of Hypertension. 2006;24:159-159.
30.    Fortunato JE, Diz DI, Shaltout HA. 218.  Fludrocortisone acetate improves baroreflex sensitivity and heart rate variability during tilt in children with postural orthostatic tachycardia syndrome. Hypertension 58: e117, 2011

Quick Reference

Hypertension & Vascular Research Center
Debra I. Diz, PhD
Program Director

Phone: 336-716-2150
FAX: 336-716-2456

Janie Marshall

Phone: 336-716-1080

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Last Updated: 01-22-2014
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