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European Journal of Heart Failure 2007 9(5):477-483; doi:10.1016/j.ejheart.2006.11.005
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© 2006 European Society of Cardiology

Non-invasive radial pulse wave assessment for the evaluation of left ventricular systolic performance in heart failure

Jean-Michel Tartierea,*, Damien Logeartb, Florence Beauvaisb, Christophe Chavelasb, Lamia Kesrib, Jean-Yves Tabetb and Alain Cohen-solalb

a Department of Physiology, Lariboisière Hospital, Assistance Publique Paris, France
b Department of Cardiology, Lariboisière Hospital, Assistance Publique Paris, France

* Corresponding author. Lariboisière Hospital — Department of Physiology, 2 rue Ambroise Paré, 75475, Paris, France. Tel.: +33 1 49 95 80 88; fax: +33 1 49 95 86 71. E-mail address: jean-michel.tartiere{at}lrb.ap-hop-paris.fr


   Abstract
Top
 Abstract
1. Introduction
 2. Methodology
 3. Results
 4. Discussion
 References
 
Introduction: Left ventricular (LV) developed pressure (dP/dt) is a classical index of myocardial contractility related to prognosis during heart failure. We sought to assess the reproducibility and feasibility of use of the maximal first derivative of the radial pulse, Rad dP/dt, as a peripheral criterion of ventricular contractility in patients with heart failure.

Methods: We assessed 50 consecutive, patients with heart failure using aplanation tonometry to record the radial pulse wave and calculate Rad dP/dt. Echocardiography, Doppler flow and tissue Doppler imaging were used to record classical parameters of LV function: LV ejection fraction (LVEF), Tei index, dP/dt on mitral regurgitation (MR dP/dt) and peak systolic velocity (S'). Total systemic vascular resistance (TSVR) was calculated by use of the Doppler calculated cardiac output. Preload was assessed by the E/Ea ratio. Feasibility was tested in an ongoing prospective mortality study (n=310).

Results: The Bland and Altman representation of repeated measurements of the Rad dP/dt showed good agreement. Feasibility was greater than 99% for a successful assessment on the right arm during the first attempt. The Rad dP/dt correlated with the LVEF, S' or Tei index as usual parameters of impaired contractility but not preload (E/Ea) or afterload (TSVR) parameters. MR dP/dt and Rad dP/dt were closely related (r=0.75, p<0.001). The ability of the arterial dP/dt to characterize LVEF was not modified by adjustment for arterial viscoelastic properties.

Conclusion: The maximal dP/dt of the radial pulse appears to be a valuable and reproducible peripheral criterion of LV systolic performance.

Key Words: Ejection fraction • Tonometry • Contractility • Heart failure • Arterial stiffness • Pulse wave

Received February 27, 2006; Revised July 28, 2006; Accepted November 27, 2006


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methodology
 3. Results
 4. Discussion
 References
 
The non-invasive assessment of left ventricular (LV) systolic function and/or contractility has long been an important issue in heart failure. Various non-invasive parameters have been evaluated, principally by echocardiography or Doppler methods and have been associated with prognosis, especially in LV systolic dysfunction [1-5]. However, all these parameters are either imprecise, or, if accurate, time-consuming and complex to assess, which implies the need for trained operators and devices that involve great cost for the medical community. Moreover, such assessment is generally underused because availability and technical or methodological limitations are generally more frequent in the general population [6,7] than in clinical studies.

The maximal value of the first derivative of the radial pulse wave (Rad dP/dt) is a possible target for assessing LV performance [8,9]. The aim of this study was to determine the feasibility, repeatability and correlation of Rad dP/dt with usual echocardiographic and Doppler parameters reflecting LV systolic performance.


   2. Methodology
Top
 Abstract
 1. Introduction
 2. Methodology
3. Results
 4. Discussion
 References
 
To be eligible for the study, patients had to have a history of acute decompensated congestive heart failure; be treated for chronic heart failure, regardless of LVEF level; and be in a stable condition at the time of examination. The diagnosis of heart failure was based on criteria defined by the European Society of Cardiology [10] and serial measurements of Brain Natriuretic Peptide [11]. All patients in the validation population (n=50) underwent complete echocardiographic assessment; the Doppler echocardiographic parameters used to demonstrate diastolic abnormality were Ea<8 cm/s or Vp<35 cm/s, with an LVEF>40%. Patients with severe mitral or aortic valvular disease or abnormal septal or lateral wall motion were excluded. All patients were followed in the Department of Cardiology of Beaujon Hospital (Clichy, France), and gave informed consent. The study was approved by the institutional review boards of the Beaujon Hospital.

Information compiled from a questionnaire completed at inclusion included sex, age, New York Heart Association (NYHA) classification and ischaemic aetiology.

Feasibility of the Rad dP/dt assessment was also tested in 310 patients participating in an ongoing prospective mortality study.

2.1. Blood pressure measurement
Brachial systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured on the right arm using an automatic sphygmomanometer (Press-Mate® 8800 C, Colin Corporation, Komaki, Japan) after 10 min of rest, with a patient lying in the supine position. Pulse pressure (PP) was defined as SBP minus DBP. Three measurements were averaged.

Radial pulse wave was recorded by aplanation tonometry on the right radial artery and calibration involved use of brachial SBP and DBP. The Rad dP/dt was found by an iterative 5-point central difference algorithm [12] that was applied over a region from the minimum point of pressure of the radial pulse to 175 ms after. Rad dP/dt was calculated automatically using the SphygmoCor® Px Pulse Wave Analysis System (AtCor Medical, West Ryde, Australia). Six measurements were averaged for statistical analysis and reproducibility was tested between 1, 2 and 3 consecutive measurements.

2.2. Echocardiographic and doppler measurements
Images were taken using a commercially available machine (Vivid 7® Vingmed-General Electrics, Horten, Norway), and data analysis was performed offline using the Echopac system. Peak velocities of the E wave and aortic flow were derived from pulsed Doppler recordings of the mitral inflow and aortic outflow. Tei index and cardiac output (CO, l/min) were calculated as described previously [2,4,13,14]. Total systemic vascular resistance (TSVR, dyne s cm–5) was calculated from mean radial blood pressure (MBP) using the formula (MBPx79.9)/CO. For tissue Doppler imaging recordings, from the apical window the sample volume was located at the septal and lateral site of the mitral annulus in the 4-chamber view. Peak systolic velocity (S') and peak early diastolic velocity (Ea) were obtained at each site [15,16] and the averaged values were used in statistical analysis. The E/Ea ratio was used as a marker of LV filling pressure regardless of LVEF [17,18] or atrial fibrillation [19]. LVEF was calculated by the Simpson method according to the recommendations for quantification of the left ventricle by 2-D echocardiography, as LV end diastolic diameter (LVEDD) [20]. LV rate of pressure increase as an approximation of the true LV dP/dt was assessed using mitral regurgitation (MR dP/dt) as described [21], when possible for 35 patients (19 with low LVEF and 16 with preserved LVEF).

All echocardiographic and Doppler measurements were taken at least 4 times and averaged. Echocardiographic and Doppler measurements and Rad dP/dt values were assessed by the same observer who was blinded to the Rad dP/dt values at the time of examination.

2.3. Assessment of arterial properties
In the ongoing prospective mortality study (n=310), a subgroup of 46 patients was analysed, in whom Rad dP/dt and the dP/dt using the carotid pulse wave (Car dP/dt) were available at the time of the analysis. We analysed the relation between these 2 measurements and the carotido femoral pulse wave velocity (CF-PWV), the carotido radial PWV (CR-PWV), the carotid augmentation index (Car AIx) and the carotid time from the foot of the carotid pulse wave and the first peak (Car Tr), representing the time from the beginning of systolic wave to the beginning of the reflected pulse wave in order to understand the possible modifications of the pulse wave shape by the arterial viscoelastic properties and the wave reflection. Measurements of these parameters were performed double blind and as described previously with the SphygmoCor® Px Pulse Wave Analysis System and Pulse Wave Velocity System (AtCor Medical, West Ryde, Australia) [22-25].

In the validation population (n=50) who underwent a complete echocardiographic assessment, viscoelastic arterial properties were assessed using the estimated aortic Tr and AIx by use of a transfer function [24] and by calculation of total arterial compliance, estimated by use of the stroke volume to estimated aortic pulse pressure (SV/PPaortic) ratio as previously described [26,27].

2.4. Statistical analysis
Statistical analysis was performed using NCSS 6.0.21 software. A p value<0.05 was considered significant for a two-tailed comparison. The agreement level between Rad dP/dt measurements was assessed by the Bland and Altman method and by plotting the difference against the mean value and its 95% confidence interval (95% CI) [28]. Spearman-rank test was used for calculating correlation. Continuous data were expressed as means±standard deviation. The Wilcoxon rank-sum and Fisher exact tests were used to compare groups with a LVEF below (≤40%) and within (>40%) the normal range. A general linear model of ANOVA was used in term to compare the adjusted dP/dt values between groups of LVEF levels after adjustment for arterial viscoelastic properties. Sensitivity, specificity, and positive and negative predictive values for the Rad dP/dt to predict an LVEF ≤40% were assessed using the receiver-operating characteristic (ROC) curve method and the maximum likelihood ratio.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methodology
 3. Results
4. Discussion
 References
 
3.1. Characteristics of the populations
Table 1 shows clinical characteristics of the validation population (n=50) according to LVEF. Patients with preserved LVEF were older. A low LVEF was associated with low CO and high TSVR, low SBP and PP, and signs of impaired contractility as assessed by S', Tei index, Rad dP/dt and MR dP/dt. LV pressure was not statistically different, as judged by E/Ea ratio, and corresponded to NYHA class. As expected, LVEDD was greater in the low LVEF group. There were no differences between groups for Tr, AIx or SV/PPaortic ratio.


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  		Table 1 Clinical haemodynamic, Doppler and echocardiographic characteristics of the validation population according to left ventricular ejection fraction (LVEF)

 
Characteristics of patients in the ongoing mortality study (n=310) were: age 68±14 years, 30% male, mean NYHA class 2.3±0.9, 44% had ischaemic heart failure aetiology, 10% non-sinus rhythm, and mean LVEF was 37±17%. Mean Rad dP/dt was 710±370 mm Hg/s, CF-PWV 9.85±3.14 m/s, CR-PWV 10.10±1.67 m/s, Car Tr 124±24 ms, and Car AIx 104±24%. CR-PWV and Car Tr were significantly higher and CF-PWV and Car AIx significantly lower for LVEF ≤40% (p<0.01 for all).

In the ongoing mortality study population, drug use was: beta blockers (76%), angiotensin-converting enzyme inhibitors and/or angiotensin 2 receptor blockers (85%), diuretics (80%), spironolactone (30%), digoxin (7%), amiodarone (23%), statins (48%) and aspirin (50%), respectively.

3.2. Reproducibility of the method
In the validation population (n=50) correlation coefficients and mean absolute differences between 1, 2 and 3 repeated measurements were: r=0.973, p<0.001; r=0.994, p<0.001; and r=0.993, p<0.001; 36±36 mm Hg/s, 22±25 mm Hg/s, 22±23 mm Hg/s, respectively. The Bland and Altman representation of the mean difference between the 3 first and the 3 last measurements are shown in Fig. 1, showing good agreement with no major outliers.


Figure 01
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  		Fig. 1 Bland and Altman representation of the reproducibility of the average of 3 Rad dP/dt measurements in the validation population. SD: standard deviation.

 
In the prospective mortality study (n=310), correlation coefficients and mean absolute difference between the first and the second measurements were: r=0.975, p<0.001 and 49±65 mm Hg/s, respectively.

3.3. Feasibility of the method
Feasibility was good in the prospective mortality study (n=310) with only one measurement being impossible to take in the right arm because of a right subclavian arterial stenosis; however, measurement was possible in the left arm. Two measurements were not recorded at the first attempt because of very low blood pressure, but were successfully recorded a few days later. Therefore, feasibility was greater than 99% for a successful assessment on the right arm on the first attempt.

3.4. Relation between Rad dP/dt and Doppler parameters
In the validation population, Rad dP/dt related strongly with the markers of LV contractility MR dP/dt (r=0.75, p<0.001, equation of linear regression y=0.6355+235.8956x, Fig. 2). Bland and Altman representation of the differences between Rad dP/dt and MR dP/dt (Fig. 3) showed moderate agreement with no major outliers, but with moderate dispersion of differences. The same correlation remained highly significant after adjustment for age and sex (r=0.73, p<0.001, Table 2). This correlation remain highly significant after adjustment for SV/PPaortic (r=0.74, p<0.001), or Tr (r=0.72, p<0.001), or AIx (r=0.73, p<0.001) or for the three parameters (r=0.61, p<0.001).


Figure 02
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  		Fig. 2 Scatterplot of Rad dP/dt and MR dP/dt values in the validation population. White circles: patients with reduced left ventricular ejection fraction (≤40%). Grey squares: patients with preserved left ventricular ejection fraction (>40%).

 


Figure 03
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  		Fig. 3 Bland and Altman representation of the accuracy of the Rad dP/dt measurement compared to the MR dP/dt in the validation population. SD: standard deviation.

 


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  		Table 2 Correlation coefficients between echocardiographic and Doppler parameters in the validation population and according to left ventricular ejection fraction (LVEF)

 
In the same population Rad dP/dt related with S', LVEF (Fig. 4) and Tei index but not preload or after load markers as assessed by the E/Ea ratio (r=–0.11, p>0.1) and TSVR (r=–0.26, p>0.05, Fig. 5). These correlations were not significantly modified after adjustment for age and sex (Table 2). The correlation between MR dP/dt and one measurement of Rad dP/dt or the average of two or three measurements was 0.65, 0.65 and 0.64, respectively (p<0.001 for all). A positive correlation was found between Rad dP/dt and impaired LV relaxation as assessed by Ea. Comparatively, MR dP/dt and S' were correlated with LVEF and Tei index to the same extent, but both parameters were correlated with the preload parameter E/Ea (r=0.33, p<0.05; and r=–0.54, p<0.001, respectively), and with the after load parameter TSVR only for S' (r=–0.42, p<0.01). These correlations were not significantly modified after adjustment for age and sex, except for E/Ea and MR dP/dt, and TSVR and S' (Table 2).


Figure 04
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  		Fig. 4 Scatterplot of Rad dP/dt and left ventricular ejection fraction (LVEF) values in the validation population. White circles: patients with reduced left ventricular ejection fraction (≤40%). Grey squares: patients with preserved left ventricular ejection fraction (>40%).

 


Figure 05
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  		Fig. 5 Scatterplot of Rad dP/dt and total systemic vascular resistance (TSVR) values in the validation population. White circles: patients with reduced left ventricular ejection fraction (≤40%). Grey squares: patients with preserved left ventricular ejection fraction (>40%).

 
In the low LVEF subgroup, Rad dP/dt and parameters of contractility were correlated with MR dP/dt and Tei but not with S' (r=0.09, p>0.1) and LVEF (r=0.39, p<0.1) and not with pre-or after load parameters. Correlation was again seen between MR dP/dt and S' but with lower significance. After adjustment for age and sex Rad dP/dt related significantly with MR dP/dt (Table 2).

In the subgroup with a preserved LVEF, Rad dP/dt was correlated with MR dP/dt and S', but not LVEF, Tei index, and with pre-or after load parameters. The MR dP/dt and S' tended to be associated, as in the total validation population, with increased E/Ea ratio (p<0.1 and p<0.01, respectively). Correlations with other parameters of contractility were less significant as for Rad dP/dt. After adjustment for age and sex Rad dP/dt related significantly with MR dP/dt (Table 2).

Sensitivity, specificity, and the positive and negative predictive value of the technique to predict a LVEF ≤ or >40% were 96%, 38%, 59% and 91%, respectively, for a threshold of 916 mm Hg/s. The ability of the brachial PP and the radial dP/dt to characterize LVEF were similar. Areas under the ROC curve were 0.83±0.18 and 0.81±0.18, respectively.

3.5. Relationship between Rad dP/dt and arterial properties
In the subgroup of 46 patients from the mortality study, with 2 Rad dP/dt and 2 Car dP/dt available, the mean±SD of Rad dP/dt and Car dP/dt, the coefficient correlation between both methods, and the mean difference were 696±291 mm Hg/s, 539±227 mm Hg/s, r=0.83, p<0.001 and 157±151, p<0.001, respectively. The increase in dP/dt between the carotid artery and radial artery was not correlated with CF-PWV, CR-PWV, Car Tr, or Car AIx (r=–0.05, r=0.08, r=0.03 and r=0.13, respectively [p>0.38 for each]). Rad dP/dt and Car dP/dt were correlated with CF-PWV (r=0.34, p=0.02 and r=0.38, p=0.008, respectively) but not with CR-PWV or Car Tr. Car dP/dt was correlated with Car AIx (–0.29, p=0.05) but not Rad dP/dt. Rad dP/dt and Car dP/dt were higher for patients with a LVEF >40% than others (846±345 versus 630±269 mm Hg/s, p=0.03; 657±296 versus 480±187 mm Hg/s, p=0.02) and this difference remained highly significant after adjustment for viscoelastic properties (p<0.05 for all) excepted concerning Rad dP/dt and Car Tr (p=0.06) or full adjustment (p=0.07).

In the mortality study (n=310) correlations between Rad dP/dt and CF-PWV, CR-PWV, Car Tr and Car AIx were: r=0.53, p<0.001; r=–0.06, p=0.3; r=–0.29, p<0.001; r=0.23, p<0.001, respectively. Rad dP/dt was higher for patients with a LVEF >40% than for those with LVEF ≤40% (900±296 versus 580±386 mm Hg/s, p<0.001) and this difference remained highly significant after adjustment for CF-PWV or CR-PWV or Car Tr or Car AIx or all (p<0.001 for each test).

In the group of 50 patients with a complete echocardiographic assessment (validation population), the Rad dP/dt was significantly different between groups before (p<0.001) or after adjustment for AIx, Tr or SV/PPaortic (p<0.001 for all) or after adjustment for all (p=0.01).


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methodology
 3. Results
 4. Discussion
References
 
The present study demonstrates that the non-invasive assessment of Rad dP/dt is a good peripheral criterion of LV systolic performance, whatever the LVEF, without major influence of the loading conditions. This parameter appears to be reproducible and easily recordable, which should ensure extensive use in general practice if clinical interest is confirmed.

During early systole, the left ventricle acts predominantly as a pressure generator to control the maximal rate of increase in LV pressure. With no aortic stenosis and if the pressure gradient due to the inertia of the blood during acceleration is ignored, this maximal rate of increase is approximately equal to the rate of increase in the ascending aortic pressure during early ejection [29]. Previous studies have used as a haemodynamic index the wave intensity index, defined as (dP/dt) (dU/dt) at any site of the circulation, where dP/dt and dU/dt are the derivatives of blood pressure and velocity, respectively, with respect to time [8,9]. The magnitude of the first peak of this wave intensity index could be derived as (dP/dt)2/{rho}c, where {rho} is blood density and c pulse wave velocity. This first peak, using Car dP/dt, has been shown to be closely related to the actual LV dP/dt (r=0.74, p<0.001) in patients with suspected coronary disease [9]. However, c is a marker of aortic stiffness independent of LV contractility, and {rho} can reasonably be assumed as a constant, which implies that the major element of this relation should be the arterial dP/dt. This relation is confirmed in the present study by the correlation between Rad dP/dt and MR dP/dt (r=0.75, p<0.001). Nevertheless, the Rad dP/dt and the MR dP/dt are not equal as it is shown by the Bland and Altman representation: firstly, because the Rad dP/dt occurred after the aortic valve opening and not the MR dP/dt, and secondly because the Rad dP/dt is potentially modified by the arterial properties. However, we have shown a significant correlation between Rad dP/dt and different markers of LV contractility related to cardiovascular prognosis [1-5] and the ability to characterise the LVEF level remains significant after adjustment for arterial properties. Moreover, it is interesting to note that Rad dP/dt and LVEF were correlated only in the validation population, whereas correlations with MR dP/dt remained significant whatever the LVEF. This result confirms the possible coexistence of impaired myocardial contractility with preserved LVEF [3].

As the pressure pulse travels along the arterial tree, its morphology is continuously being modified by the local viscoelastic properties and by the addition of the reflected waves. These modifications are associated with a modification of the place of the first derivative of the radial pulse [25] with a systematic error and underestimation of the time delay between 2 measurement points when used for PWV assessment. However, this study confirms a systematic error in the determination of the arterial dP/dt, despite a maintained correlation (r=0.83, p<0.001) between Car and Rad dP/dt. Without direct comparison, the differences between the Rad dP/dt and MR dP/dt seem to be less important than differences between the Rad dP/dt and Car dP/dt. In this study, the modification of the dP/dt value along the brachial artery was not related to viscoelastic properties, wave reflection amplitude, or time delay. Brinton et al. [30] have studied how pulsations in a blood pressure cuff can be used to produce information on vascular compliance. In their equation, the dP/dt max of the brachial artery is included in the denominator as an estimator of vascular compliance. Our results are consistent with these authors, showing a significant correlation between arterial dP/dt and the stroke volume to central pulse pressure ratio or the CF-PWV or the Tr. However, in the present study differences in dP/dt between low LVEF and preserved LVEF patients are maintained even after adjustment for arterial properties and especially for the CR-PWV. Moreover, Kawaguchi et al. [31] have shown that LV end-systolic elastance is inversely related to arterial compliance as a witness of combined ventricular arterial stiffening. Because the increase of the dP/dt value along the arterial tree is not related to arterial properties and the correlation between Car dP/dt and Rad dP/dt appears to be strictly linear our data are consistent with previous studies showing that linear transformation of the arterial pulse shape from the radial artery permits a good estimation of the central pulse wave [24]. Therefore, if the value of the first derivative of the arterial pulse is clearly amplified during travel in the arterial tree, the ability of the radial dP/dt to characterize LV contractility is probably not affected. However, this possible bias should be analysed in a prospective study.

Since MR dP/dt is always calculated between 1 and 3 m/s, it is always determined at a constant developed pressure almost invariably prior to the opening of the aortic valve. Thus, the technique may have an advantage over assessing the Rad dP/dt, which occurs after the opening of the aortic valve and may be more affected by after load variables. However, the present study shows only a non-significant correlation between Rad dP/dt and total systemic vascular resistance regardless of LVEF. This limitation is of major importance and should be confirmed by further studies involving invasive assessment of systemic vascular resistance. This study also shows that Rad dP/dt is independent of LV filling pressure as defined by the E/Ea ratio [17-19].

In conclusion, the maximal dP/dt of the radial pulse appears to be a good and reproducible peripheral criterion of LV systolic performance. Ultimately, the technique should be judged on its ability to contribute to the clinical management of the patient, and our study suggests that this method has potential to do so. The ongoing mortality study should provide additional data on the feasibility of this assessment method.


   Acknowledgement
 
This study was supported by a grant from the French Society of Cardiology.


   References
Top
 Abstract
 1. Introduction
 2. Methodology
 3. Results
 4. Discussion
 References
 

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