Ahmad Qasem

Validation of a Generalized Transfer Function to Noninvasively Derive Central Blood Pressure During Exercise

Exercise brachial blood pressure (BP) predicts mortality, but because of wave reflection, central (ascending aortic) pressure differs from brachial pressure. Exercise central BP may be clinically important, and a noninvasive means to derive it would be useful. The purpose of this study was to test the validity of a noninvasive technique to derive exercise central BP. Ascending aortic pressure waveforms were recorded using a micromanometer-tipped 6F Millar catheter in 30 patients (56±9 years; 21 men) undergoing diagnostic coronary angiography. Simultaneous recordings of the derived central pressure waveform were acquired using servocontrolled radial tonometry at rest and during supine cycling. Pulse wave analysis of the direct and derived pressure signals was performed offline (SphygmoCor 7.01). From rest to exercise, mean arterial pressure and heart rate were increased by 20±10 mm Hg and 15±7 bpm, respectively, and central systolic BP ranged from 77 to 229 mm Hg. There was good agreement and high correlation between invasive and noninvasive techniques with a mean difference (±SD) for central systolic BP of −1.3±3.2 mm Hg at rest and −4.7±3.3 mm Hg at peak exercise (for both r=0.995; P<0.001). Conversely, systolic BP was significantly higher peripherally than centrally at rest (155±33 versus 138±32 mm Hg; mean difference, −16.3±9.4 mm Hg) and during exercise (180±34 versus 164±33 mm Hg; mean difference, −15.5±10.4 mm Hg; for both P<0.001). True myocardial afterload is not reliably estimated by peripheral systolic BP. Radial tonometry and pulse wave analysis is an accurate technique for the noninvasive determination of central BP at rest and during exercise.

Basal NO Locally Modulates Human Iliac Artery Function In Vivo

We demonstrated previously that endogenous NO influences large-artery distensibility in the ovine hindlimb. However, the role of basal NO in larger human conduit arteries is controversial. The aim of this study was to investigate whether basal production of NO, acting locally, influences iliac artery distensibility in humans. Distensibility was assessed by intra-arterial measurement of the pulse wave velocity. Eighteen subjects, free of significant coronary or iliac artery disease, were studied after diagnostic cardiac catheterization. Simultaneous pressure waveforms were recorded with a high-fidelity dual-pressure sensing catheter, placed in the common iliac artery during intra-arterial infusion of saline (baseline), glyceryl trinitrate (4 nmol/min), or NG-monomethyl-l-arginine (8 and 16 &mgr;mol/min). Drugs were infused proximally, via the catheter to perfuse the segment of artery under study, or distally, via the sheath, to control for any reflex changes in flow or sympathetic activation. Velocity was calculated using the foot-to-foot methodology. Six subjects received glyceryl trinitrate and 12 NG-monomethyl-l-arginine. There was no change in velocity after infusion of glyceryl trinitrate or NG-monomethyl-l-arginine via the sheath. However, infusion of glyceryl trinitrate via the catheter significantly reduced velocity by 31.43±5.80% (mean±SEM; P<0.01; P=0.02 for comparison). Likewise, infusion of the highest dose of NG-monomethyl-l-arginine via the catheter significantly increased velocity by 27.25±8.20% (P=0.001; P=0.02 for comparison). Importantly, there was no change in mean arterial blood pressure throughout the studies. These data indicate that under resting conditions, local NO production modulates human iliac artery distensibility and that exogenous NO increases arterial distensibility.

Nebivolol Increases Arterial Distensibility In Vivo

Arterial stiffness is a key determinant of cardiovascular risk in hypertensive patients. &bgr;-Blockers appear to be less effective than other drugs in improving outcome in hypertensive patients, and a potential explanation may be that &bgr;-blockers are less effective in reducing arterial stiffness. The aim of this study was to assess the direct effect of &bgr;-blockade on pulse wave velocity (PWV), a robust measure of arterial distensibility, using a local, ovine, hind-limb model. In addition, we hypothesized that the vasodilating &bgr;-blocker nebivolol, but not atenolol, would increase arterial distensibility in vivo. All studies were conducted in anesthetized sheep. PWV was recorded in vivo using a dual pressure-sensing catheter placed in the common iliac artery. Intraarterial infusion of nebivolol reduced PWV by 6±3% at the higher dose (P<0.001), but did not alter mean arterial pressure (change of −1±3 mm Hg, P=0.1). In contrast, atenolol had no effect on PWV (P=0.11) despite a small drop in mean pressure (change of −5±3 mm Hg, P<0.01). Infusion of glyceryl trinitrate led to a dose-dependent fall in PWV, and 2 nmol/min produced a similar reduction in PWV to the higher dose of nebivolol (500 nmol/min). The effect of nebivolol on PWV was significantly attenuated during coinfusion of NG-monomethyl-l-arginine (P=0.003) and also during coinfusion of butoxamine (P=0.02). These results demonstrate that nebivolol, but not atenolol, increases arterial distensibility. This effect of nebivolol is mediated through the release of NO via a &bgr;2 adrenoceptor–dependent mechanism. Thus, nebivolol may be of benefit in conditions of increased large artery stiffness, such as isolated systolic hypertension.

Peripheral “Oscillatory” Compliance Is Associated With Aortic Augmentation Index

The augmentation index (AIx) and “oscillatory” compliance (C2) are wave contour analysis parameters for the central aorta (Pao) and radial artery pressure wave (Prad), respectively. Both are sensitive to cardiovascular risk factors such as aging, hypertension, and diabetes and have been proposed as prognostic markers for cardiovascular disease. In this work, we studied the relation between both. We first calculated Prad corresponding to a typical aortic A-type (AIx >0.15) and C-type wave (AIx <0), taken from the literature, by using a generalized aorta-radial pressure transfer function. Prad corresponding to C-type waves yielded the highest C2 value. We further used simultaneously measured aortic and radial artery pressure in 45 human subjects age 34 to 84 years (63±12 [SD]) at baseline and after administration of nitroglycerin to calculate AIxmeas and C2, respectively. Transfer function was used to calculate reconstructed aortic pressure and AIxrec. AIxrec underestimates AIxmeas by 0.03±0.16, but both values correlate well (r =0.64;P <0.001). C2 and AIx were inversely correlated (r =−0.36;P <0.001 for AIxmeas;r =−0.30;P <0.01 for AIxrec). Both AIxmeas (0.06±0.17 versus 0.20±0.21;P <0.01) and AIxrec (0.04±0.12 versus 0.16±0.16;P <0.001) were lower after nitroglycerin, whereas C2 increased only nonsignificantly (0.080±0.036 versus 0.071±0.042). C2 is related to AIx and reflects, at least in part, hemodynamic changes affecting central aortic pressure. Nevertheless, given the model assumptions and computational steps associated with calculating C2, AIx could be a more appropriate parameter to use in the clinical setting because it is determined directly from the pressure wave contour.

Blood pressure waveform analysis by means of wavelet transform

The assessment of cardiovascular function by means of arterial pulse wave analysis (PWA) is well established in clinical practice. PWA is applied to study risk stratification in hypertension, with emphasis on the measurement of the augmentation index as a measure of aortic pressure wave reflections. Despite the fact that the prognostic power of PWA, in its current form, still remains to be demonstrated in the general population, there is general agreement that analysis and interpretation of the waveform might provide a deeper insight in cardiovascular pathophysiology. We propose here the use of wavelet analysis (WA) as a tool to quantify arterial pressure waveform features, with a twofold aim. First, we discuss a specific use of wavelet transform in the study of pressure waveform morphology, and its potential role in ascertaining the dynamics of temporal properties of arterial pressure waveforms. Second, we apply WA to evaluate a database of carotid artery pressure waveforms of healthy middle-aged women and men. Wavelet analysis has the potential to extract specific features (wavelet details), related to wave reflection and aortic valve closure, from a measured waveform. Analysis showed that the fifth detail, one of the waveform features extracted applying the wavelet decomposition, appeared to be the most appropriate for the analysis of carotid artery pressure waveforms. What remains to be assessed is how the information embedded in this detail can be further processed and transformed into quantitative data, and how it can be rendered useful for automated waveform classification and arterial function parameters with potential clinical applications.

Carotid-femoral pulse wave velocity assessment using novel cuff-based techniques: comparison with tonometric measurement.

Background: Carotid-femoral pulse wave velocity, a predictor of cardiovascular outcome, is conventionally measured using a tonometer sequentially placed upon the carotid and femoral arteries, gated using an electrocardiogram. Leg cuff detection of the femoral pulse removes the need for signal gating, reduces the time required for a single measurement, but gives different pulse wave velocity values to tonometric analysis. A novel algorithm to correct for the transit time and distance related to the additional femoral segment was applied to the cuff-based approach in this study. Method: Eighty-eight individuals were recruited across four centres and carotid-femoral pulse wave velocity measured in triplicate using two operators with both a tonometer-based device and a device using an inflated thigh cuff with and without the use of the novel algorithm. Comparison was made by Bland–Altman and regression analysis. Results: The unadjusted cuff-based approach gave lower pulse wave velocity values than the tonometer-based approach (6.11 ± 1.27 and 7.02 ± 1.88 m/s, P < 0.001). With application of the algorithm, the cuff-based device gave similar pulse wave velocity values (7.04 ± 1.72 m/s) as the tonometer-based approach (P = 0.86). Analysis of covariance with age showed a difference between the tonometer and cuff-based methods (P < 0.001), with a dependence upon age (P = 0.004). The adjusted cuff-based method gave similar results to the tonometer-based method (P = 0.94), with no dependence upon age (P = 0.46). Conclusion: This study provided validation of a cuff-based assessment of carotid-femoral pulse wave velocity against the universally accepted tonometric method. Adjusting the cuff-based method for the additional femoral segment measured gives results comparable to the tonometer-based method, for which the majority of population data exist to date.

Estimation of central aortic pressure waveform features derived from the brachial cuff volume displacement waveform

There is increasing interest in non-invasive estimation of central aortic waveform parameters in the clinical setting. However, controversy has arisen around radial tonometric based systems due to the requirement of a trained operator or lack of ease of use, especially in the clinical environment. A recently developed device utilizes a novel algorithm for brachial cuff based assessment of aortic pressure values and waveform (SphygmoCor XCEL, AtCor Medical). The cuff was inflated to 10 mmHg below an individuals diastolic blood pressure and the brachial volume displacement waveform recorded. The aortic waveform was derived using proprietary digital signal processing and transfer function applied to the recorded waveform. The aortic waveform was also estimated using a validated technique (radial tonometry based assessment, SphygmoCor, AtCor Medical). Measurements were taken in triplicate with each device in 30 people (17 female) aged 22 to 79 years of age. An average for each device for each individual was calculated, and the results from the two devices were compared using regression and Bland-Altman analysis. A high correlation was found between the devices for measures of aortic systolic (R2=0.99) and diastolic (R2=0.98) pressure. Augmentation index and subendocardial viability ratio both had a between device R2 value of 0.82. The difference between devices for measured aortic systolic pressure was 0.5±1.8 mmHg, and for augmentation index, 1.8±7.0%. The brachial cuff based approach, with an individualized sub-diastolic cuff pressure, provides an operator independent method of assessing not only systolic pressure, but also aortic waveform features, comparable to existing validated tonometric-based methods.

Radial pressure waveform dP/dt max is a poor indicator of left ventricular systolic function

Background  The first derivative of left ventricular (LV) pressure over time (dP/dt max) is a marker of LV systolic function that can be assessed during cardiac catheterization and echocardiography. Radial artery dP/dt max has been proposed as a possible marker of LV systolic function and we sought to test this hypothesis.

Clinical Assessment of Wave Reflection

To the Editor: In their paper on wave reflection, Millasseau et al1 questioned whether quantification of wave reflection phenomena required synthesis of the ascending aortic waveform from the radial pulse through use of a generalized transfer function, or whether similar information could be extracted directly from the radial pulse. We had introduced the SphygmoCor™ system, not only to study central hemodynamics, but also because we could not reliably or consistently identify evidence of wave reflection on the falling systolic limb of the radial waveform. Problems were most commonly encountered when augmentation was low, or wave reflection came late (young persons), or was reduced by vasodilator therapy, or when heart rate was fast and augmentation obscured by the cardiac incisura. By generating aortic pressure, we sought to eliminate the effects of wave reflection within the upper limb so that we could determine effects of reflection from all parts of the body on aortic pressure throughout systole and on left ventricular load. The validity of this system has been confirmed,2 as has its reproducibility.3 Absolute synthesized values are …

Large Artery Stiffness Assessment Using SphygmoCor Technology

Large artery stiffness assessment has been an integral part of the SphygmoCor technology since 1998. Aortic stiffness is approximated with non-invasive measurement of carotid-femoral pulse wave velocity, with improvements made with time to make the assessment procedure quicker and more user independent. Also standard in the devices is the ability to reliably calculate the central aortic waveform shape from a peripheral pressure waveform from either the brachial or radial artery. This waveform contains much information beyond peak and trough (systolic and diastolic pressure). Relative waveform features such as the augmentation index, wave reflection magnitude, reflection time index, and subendocardial viability ratio are parameters that are influenced by the stiffness of systemic arteries. This article briefly describes these parameters related to large artery stiffness and provides reference to validation and repeatability studies relative to the clinical use of the SphygmoCor devices. It is beyond the scope to review here the 424 original research articles that have employed SphygmoCor devices in measuring arterial stiffness. Instead, the method of measurement across the devices is described, including tonometry, volumetric displacement through cuff placement around limbs, and ambulatory monitoring. Key population and subpopulation studies are cited where the average stiffness parameter progression with age and gender, as measured by SphygmoCor devices, is quantified in the healthy and general population. Finally, with reference to guidelines from working groups on arterial stiffness and hypertension, the clinical utility of large artery stiffness measurement is discussed in the context of the arterial stiffness parameters provided by the SphygmoCor systems.