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Am J Physiol Heart Circ Physiol 289: H2081-H2088, 2005. First published June 3, 2005; doi:10.1152/ajpheart.00951.2004
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Relationship of diastolic intraventricular pressure gradients and aerobic capacity in patients with diastolic heart failure

Aleksandr Rovner,1 Neil L. Greenberg,2 James D. Thomas,2 and Mario J. Garcia2

1Department of Cardiology, Barnes Jewish Hospital, St. Louis, Missouri; and 2Department of Cardiovascular Imaging, Cleveland Clinic Foundation, Cleveland, Ohio

Submitted 10 September 2004 ; accepted in final form 25 May 2005


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
We sought to elucidate the relationship between diastolic intraventricular pressure gradients (IVPG) and exercise tolerance in patients with heart failure using color M-mode Doppler. Diastolic dysfunction has been implicated as a cause of low aerobic potential in patients with heart failure. We previously validated a novel method to evaluate diastolic function that involves noninvasive measurement of IVPG using color M-mode Doppler data. Thirty-one patients with heart failure and 15 normal subjects were recruited. Echocardiograms were performed before and after metabolic treadmill stress testing. Color M-mode Doppler was used to determine the diastolic propagation velocity (Vp) and IVPG off-line. Resting diastolic function indexes including myocardial relaxation velocity, Vp, and E/Vp correlated well with O2 max (r = 0.8, 0.5, and –0.5, respectively, P < 0.001 for all). There was a statistically significant increase in Vp and IVPG in both groups after exercise, but the change in IVPG was higher in normal subjects compared with patients with heart failure (2.6 ± 0.8 vs. 1.1 ± 0.8 mmHg, P < 0.05). Increase in IVPG correlated with peak O2 max (r = 0.8, P < 0.001) and was the strongest predictor of exercise capacity. Myocardial relaxation is an important determinant of exercise aerobic capacity. In heart failure patients, impaired myocardial relaxation is associated with reduced diastolic suction force during exercise.

metabolic stress test; cardiovascular system; oxygen metabolism

WHILE A GREAT DEAL IS KNOWN about the causes that lead to the development of cardiac failure, the specific hemodynamic alterations that lead to the appearance of symptoms are less well understood (4, 28). Several factors are known to determine exercise aerobic capacity. In most normal individuals, the limiting factors that influence O2 max are the skeletal muscle mass and the capacity of the cardiovascular system (49). In patients with heart failure, the exercise capacity may be limited by the number of frequently coexisting factors such as decreased contractility, diastolic dysfunction, chronotropic incompetence, oxygen metabolism, or skeletal muscle mass (13). During peak exercise, the duration of diastasis is greatly diminished to account for the increase in heart rate (HR). Yet, for the heart to increase the cardiac output, the diastolic mechanics must adjust to the decrease in time to fill (48). The ability to accommodate high volume loads has been demonstrated in athletes (31). This is done at low filling pressures; rather, the early relaxation is increased to provide for a "suction" force and high left ventricular (LV) compliance. The notion that the LV functions as a suction pump was demonstrated by Katz (21). Attempts have been made to identify the structures that provide the spring for the LV to develop negative pressure in early diastole (44). However, patients with heart failure may not be able to achieve this necessary increase in diastolic relaxation to accommodate the preload increase (3, 18, 24).

Until recently, the echocardiographic assessment of diastolic function was limited to standard pulsed Doppler indexes. Because these indexes are confounded by filling pressures and HR, they have limited utility in determining specific alterations in any individual physiological parameter, particularly in heart failure patients where compensatory preload augmentation results in pseudonormalization of many flow-based indexes (46). Newer Doppler indexes of diastolic function, including tissue Doppler-derived relaxation velocity (Ea) and color M-mode Doppler early filling propagation velocity (Vp), have been shown to be less sensitive to preload alterations and to provide an accurate assessment of LV relaxation. We recently demonstrated that diastolic intraventricular pressure gradients (IVPG), a marker of LV suction, can be accurately estimated from quantitative analysis of the spatiotemporal distribution of color M-mode Doppler data (15). In addition, these indexes may be combined with transmitral pulsed Doppler indexes to estimate LV filling pressures (10, 39).

In accordance, the aims of the present study were to 1) determine the relationship between myocardial relaxation at rest and the ability to increase IVPG during exercise, 2) establish whether the ability to increase IVPG during exercise is a determinant of aerobic capacity and whether this mechanism is impaired in patients with heart failure, and 3) determine whether the increase in IVPG acts to prevent an increase in LV filling pressures during exercise.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Study design. This study was designed as a prospective cohort evaluation and was approved by the institutional review board for human research. All participants signed an informed consent. All procedures followed institutional guidelines. Consecutive patients with a diagnosis of heart failure with LV systolic dysfunction undergoing metabolic stress testing at the Cleveland Clinic Foundation between September 14 and November 14, 2001 were recruited. Exclusion criteria were mitral valve replacement, atrial fibrillation, and inability to give informed consent. Normal volunteers between the ages of 18 and 65 years were recruited to define the normal response of diastolic indexes during metabolic exercise stress test.

Metabolic stress testing. All patients with heart failure underwent a graded treadmill exercise test using the modified Naughton protocol (40). Electrocardiogram (ECG) tracings and blood pressure were monitored during the stress test and the recovery period. The stress test was terminated when subjects indicated fatigue or if the ECG indicated an abnormal rhythm or ischemia. The metabolic component of the stress test was evaluated with a metabolic cart (MedGraphics CardiO2 combined VO2/ECG Exercise System, St. Paul, MN). Full calibration was performed daily, and autocalibration was performed before each test. Each subject was given a mouthpiece that directed samples of the inspired and expired gases to the analyzer. A nasal clip was used to prevent unaccounted air leak. The analyzer was connected to a PC computer running BreezeEx software (MedGraphics, St. Paul, MN, 1996). Metabolic parameters including the O2 max, CO2, anaerobic threshold, and tidal volume were acquired during the stress test continuously and then averaged in 30-s increments.

Normal subjects underwent a treadmill exercise test using a modified Bruce protocol where advances between stages were made in 2-min intervals. The stress test was stopped when 85% predicted HR was achieved. The metabolic part of the stress test was done in the same fashion as for the subjects with heart failure.

Echocardiographic study. Each subject underwent an echocardiographic study before the metabolic stress test and immediately after the treadmill was stopped. An ATL-HDI 5000 ultrasound machine (Advanced Technology Laboratories) equipped with a multifrequency (2.5–3.5 MHz) harmonic imaging transducer and digital storage capabilities was used. LV volumes and ejection fraction were assessed from the apical four- and two-chamber views using Simpson’s biplane method. Wall thickness and chamber diameter were measured from parasternal long axis view. Pulsed Doppler examination at the mitral valve leaflet tips was performed in the standard fashion. Peak early (E) and peak atrial contraction (A) velocities were recorded; the E/A ratio was calculated. Pulsed Doppler recording of the pulmonary venous flow was used to measure the peak systolic (S) and diastolic (D) velocities and to calculate S/D ratio. Tissue Doppler velocities were obtained from the basal segment of the interventricular septum at the four-chamber view and the early diastolic (Ea) velocity was recorded (12). Color M-mode Doppler was obtained by positioning the scan line through the mitral valve, and the sweep speed was increased to 200 mm/s to optimize the temporal resolution. Subsequently, the Nyquist limit and the color baseline were adjusted to obtain the best spatial resolution. Flow propagation velocity (Vp) was measured as the slope of the first color aliasing starting at the mitral valve leaflets and moving 4 cm into the ventricular cavity (10). The index E/Vp was used to assess LV filling pressures as previously reported by our group (10). LV outflow tract (LVOT) diameter was measured from the parasternal long view and LVOT velocity time integral (VTI) was obtained from the five-chamber view. Cardiac output was calculated as follows:

Echocardiographic images after stress test were obtained in the following order: 1) color M-mode Doppler, 2) mitral valve pulsed Doppler, 3) tissue Doppler, and 4) pulmonary venous pulsed Doppler. The postexercise acquisition was completed within 3.7 ± 2.4 min from termination of exercise. All variables were measured before and after the stress test for comparison.

Calculation of IVPG. The theoretical basis for noninvasive determination of the IVPG has been described elsewhere (16, 47). Briefly, the Navier-Stokes differential equation describes the three-dimensional blood flow from the left atrium (LA) into the LV through the mitral valve. To simplify it, we can assume negligible blood viscosity and a lack of turbulent flow. Because we are interested in blood velocities through the mitral valve, blood flow is assumed to be in one dimension along the scan line. Solving for the pressure, the Euler equation (1) is obtained:

(1)
Integrating the Euler equation along the mitral valve inflow from the LV base to the LV apex yields a simplified unsteady-state Bernoulli equation for incompressible fluids (2):

(2)

A custom-written software package (LabView, National Instruments) enables us to extract the color pixels from the color M-mode Doppler image, convert them into true velocities with a dealiasing algorithm using the stored Nyquist limit, calculate the derivatives, and perform noise filtering to finally arrive at the intraventricular pressure gradient between the LV base and apex during early diastole. Manual measurement of Vp data depends on the specific method used (45). In this paper, we used the methodology that was validated in our laboratory (10). However, measurement of IVPG relies on automated processing of all velocities from the color M-mode Doppler map; the actual Vp measurement is not used in the IVPG calculation.

Intra- and interobserver variability was assessed by measuring the IVPG from a randomly selected sample of 20 images by two experienced investigators (AR and NG).

Statistical analysis. Data are presented as means ± SD. All statistical calculations were done using SPSS version 10.0 for Windows (SPSS, Chicago, IL). To test the hypothesis that IVPG increase postexercise, Student’s t-test was used to compare the means. To test the hypothesis that clinical and echocardiographic variables are predictive of aerobic capacity, a stepwise multivariable regression analysis was used. Pearson correlation statistics were used to describe the relationship between normally distributed variables. Intra- and interobserver differences are reported as absolute true difference ± SD; simple linear regression was used to compare data between two readers. A P value of <0.05 was used to infer statistical significance.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 GRANTS
 REFERENCES
 
Thirty-one consecutive patients referred to the metabolic stress lab as part of their evaluation for cardiac transplant were recruited. The mean age for patients with heart failure was 53 ± 11 yr (range 37 to 74 yr), 21 (68%) were males. Table 1 presents the medication classes that patients were receiving at the time of the study. Twenty-nine patients were taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (94%) and diuretics (94%), 20 patients were taking a {beta}-blocker (65%). Clinically, all 31 patients were in New York Heart Association class II to III at the time of the metabolic stress test.


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  		Table 1. Medications taken by the CHF group

 
There were 15 normal subjects that participated in this study. The control group was somewhat younger than the heart failure group with more men present in the heart failure cohort. The mean age was 35 ± 8 yr (range 23 to 52 yr), seven (47%) were males. These subjects were not taking any medications at baseline and were free from diagnoses of heart failure, hypertension, and valvular disease. Even though no specific attempt was made to recruit athletically trained subjects, eight (53%) were engaged in aerobic exercise training.

As expected, there were significant differences between normal subjects and heart failure subjects in baseline ejection fraction, end-diastolic diameter, and LV mass (Table 2). The HR increase was more pronounced in normal subjects compared with patients with heart failure (delta HR in normal subjects was 97 ± 32 vs. 54 ± 26% in patients with heart failure, P < 0.001; Table 3). Calculated cardiac output increased to a higher magnitude in normal subjects compared with that of heart failure (151 ± 50 vs. 80 ± 60%, respectively, P < 0.001).


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  		Table 2. LV dimensions in heart failure and normal subjects

 

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  		Table 3. Diastolic characteristics before and after metabolic stress test

 
Diastolic variables at rest and after exercise. Figure 1 demonstrates the representative images on which the diastolic measurements were performed. Table 3 represents diastolic characteristics of patients with heart failure and normal subjects before and after the metabolic stress test. The peak E velocity increased with exercise in both heart failure and in normal subjects; however, the absolute increase was higher in normals. The E/A ratio increased in patients with heart failure, but in normal subjects the ratio decreased with exercise. The deceleration time (DT) had a smaller dispersion in normal subjects, in both groups the DT decreased with exercise to a statistically significant extent (from 215 ± 29 to 169 ± 42 ms for the normal subjects compared with 210 ± 102 to 152 ± 53 ms in patients with heart failure).



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  		Fig. 1. A: echocardiographic parameters of diastolic function for a patient with heart failure with stage 1 (abnormal relaxation) diastolic dysfunction. The baseline intraventricular pressure gradient (IVPG) was 1.2 mmHg and the peak exercise IVPG was 3.3 mmHg with delta IVPG = 2.1 and O2 max = 18.7. B: echocardiographic parameters of diastolic function for a patient with heart failure with stage 4 diastolic dysfunction (irreversible restriction pattern). The baseline IVPG was 2.7 mmHg and the peak exercise IVPG was 1.9 mmHg with delta IVPG = –0.8 and O2 max = 8.9. E and A, peak early and atrial contraction transmitral flow velocities, respectively. S and D, peak pulmonary venous systolic and diastolic velocities, respectively.

 
Tissue Ea velocity and Vp were significantly lower in patients with heart failure compared with normal subjects at baseline (Table 3). The magnitude of the change for tissue Ea velocity and Vp was higher after exercise in normal subjects compared with patients with heart failure, indicative of better adapted ventricular relaxation (3.6 ± 1.7 vs. 1.9 ± 2.0 cm/s and 21.0 ± 7.3 vs. 5.3 ± 6.3 cm/s, respectively, P < 0.001).

IVPG were not statistically different between heart failure patients and normal subjects at baseline (Table 3) and increased after exercise in both groups. However, normal volunteers had a significantly greater increase in IVPG compared with patients with heart failure (2.6 ± 0.8 vs. 1.1 ± 0.8 mmHg, P < 0.05), indicating greater increase in diastolic suction force.

Metabolic variables after exercise. As expected, patients with heart failure achieved a lower O2 max compared with normal subjects (16.9 ± 5 vs. 32.7 ± 8 ml·kg–1·min–1, P < 0.001). Exercise capacity as measured by metabolic equivalents was higher in normal subjects (9.4 ± 2.5 vs. 4.8 ± 1.4, P < 0.05). Both groups achieved similar respiratory exchange ratio (1.1 ± 0.12 vs. 1.1 ± 0.09, P = 0.27), indicating an adequate test performance.

Determinants of aerobic capacity. Baseline diastolic variables that correlated well with achieved O2 max included tissue Ea velocity (r = 0.8, P < 0.001), Vp (r = 0.5, P < 0.001), and E/Vp (r = –0.5, P < 0.001). Baseline E/A ratio had a direct correlation with O2 max in patients with stage 1 diastolic dysfunction (abnormal relaxation) and normal subjects (r = 0.8, P < 0.001). When baseline E/A ratio was correlated with O2 max for patients with pseudonormal pattern and restrictive (deceleration time <150 ms) diastolic physiology, an inverse correlation was observed (r = –0.6, P < 0.001), as expected.

Baseline IVPG did not correlate with achieved O2 max. However, the change in IVPG (delta IVPG), indicating the ability of the LV to increase the vigor of active relaxation and increase the ventricular suction in diastole, correlated well with O2 max (r = 0.8, P < 0.001) as demonstrated in Fig. 2. Change in calculated cardiac output also correlated with O2 max (r = 0.62, P < 0.01) and with delta IVPG (r = 0.6, P < 0.01).



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  		Fig. 2. Relationship between the change in IVPG during the metabolic stress test and the achieved O2 max.

 
Table 4 demonstrates the results of the univariate and multivariate regression between the echocardiographic variables and the aerobic capacity. Diastolic variables (delta IVPG, in particular) demonstrate an independent relationship to O2 max when combined with systolic and other diastolic data in a multivariate regression analysis.


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  		Table 4. Univariate and multivariate regression analysis between the echocardiographic variables and the aerobic capacity

 
Filling pressures at rest and after exercise. The E/Vp ratio and E/Ea ratio are closely related to the LV filling pressures as shown by Garcia et al. (10) and Nagueh et al. (37). The relationship between E/Ea and left ventricular end-diastolic pressure has also been mathematically determined and validated using simultaneous echocardiographic and invasive methods (26). Patients with heart failure had higher E/Vp and E/Ea ratios at baseline (Table 3), indicating high filling pressures.

Estimated pulmonary capillary wedge pressure in normal volunteers was 11.9 ± 1.5 mmHg at baseline as compared with 20.0 ± 3.9 mmHg in patients with heart failure (P < 0.01). The increase in filling pressures postexercise was more pronounced in patients with heart failure compared with normal subjects (29.6 ± 18.6 vs. 9.6 ± 8.9%, respectively, P < 0.01). Figure 3 demonstrates the relationship between the delta IVPG and the change in LV filling pressures (estimated from E/Vp) after the exercise test. There is a negative correlation between these two variables (r = –0.4, P < 0.01) signifying that the change in LV filling pressure and the ability to accommodate the increase in volume is closely related to the relaxation capacity of the ventricle during diastole. A similar negative correlation was elucidated between the baseline E/Ea ratio and the delta IVPG (r = –0.5, P < 0.001).



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  		Fig. 3. Relationship between the change in left ventricular (LV) filling pressures (estimated from E/Vp) and the active LV relaxation during diastole (represented by delta IVPG). PCWP, pulmonary capillary wedge pressure.

 
LV stiffness at rest and after exercise. Little and colleagues (30) developed and validated a noninvasive method of calculating the LV operating stiffness (KLV) using the DT that can be obtained from the mitral inflow Doppler. We used their method to calculate the KLV in our groups using the following equation:

As expected, the normal subjects had a less stiff heart compared with the heart failure group (0.15 ± 0.04 vs. 0.24 ± 0.2 mmHg, respectively, P < 0.05). In both groups, the KLV increased after exercise to a similar degree (normal group: from 0.15 ± 0.04 to 0.25 ± 0.1 mmHg, heart failure group: from 0.24 ± 0.2 to 0.38 ± 0.2 mmHg). The IVPG had a negative correlation with the KLV that was more pronounced after exercise in the heart failure group (r = –0.4, P < 0.05).

Intra- and interobserver variability. Twenty randomly selected color M-mode Doppler images were used to assess intra- and interobserver variability in measuring the IVPG.

The absolute true difference in measurements for intraobserver variability was 0.03 ± 0.01 mmHg, with the Pearson correlation coefficient being 0.9 (P < 0.01). The variability of measurement acquisition was less when analyzed for the subgroup of images recorded preexercise (7 cases): the absolute true difference was 0.02 ± 0.02 mmHg, and the Pearson correlation coefficient was 0.9 (P < 0.01). The analysis of data recorded postexercise (13 cases) revealed a somewhat larger data dispersion: the absolute true difference was 0.03 ± 0.01 mmHg.

The agreement for interobserver variability was equally good. Overall, the absolute true difference in measurements was 0.03 ± 0.02 mmHg, and the Pearson correlation coefficient was 0.9 (P < 0.01). As expected, there was less variability in measurements between the two readers for the preexercise data compared with the postexercise data: the absolute true difference was 0.02 ± 0.02 mmHg. The postexercise data analysis revealed more variability between the two readers: the absolute true difference was 0.03 ± 0.01 mmHg.


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
Our study demonstrated an increase in LV relaxation during diastole (inferred from the absolute increase in IVPG) with exercise in both normal subjects and in patients with heart failure. However, this mechanism was significantly impaired in the heart failure group compared with normal subjects. We provided evidence for a strong relationship between the ability to augment the diastolic LV relaxation (represented by the delta IVPG) with exercise and the O2 max. Our study also demonstrated that in patients with heart failure, the decreased ability to augment the diastolic relaxation is responsible for the inability to accommodate the increase in estimated preload during exercise, resulting in higher filling pressures.

Regional diastolic pressure differences have been identified in the left ventricle only recently and their importance in determining diastolic function now becomes evident. Ling and colleagues (25) described the suction effect that develops secondary to a pressure drop between the LV base and apex in the canine model; this suction effect aids ventricular filling. The change in these regional pressure gradients with positive and negative inotropic agents was subsequently demonstrated (5, 8). Nonuniformity of the LV and the shape change during active relaxation may account for the formation of these IVPG (38, 51). Loss of this suction effect that contributes to the rapid filling stage has been observed after experimental ischemia is produced (6). The ability to measure these gradients was cumbersome, requiring invasive high fidelity pressure monitoring. With the advent of ultrasound technology and computer programming, we can now use the color M-mode velocity information to determine the diastolic IVPG not only during resting conditions but also during exercise.

Heart failure is a multifactorial entity that combines derangements in both the systolic and diastolic function (1, 7, 24, 28, 50). As the LV remodels and preload increases, diastolic function worsens. Unfortunately, there is a parabolic relationship between the indexes based on pulsed Doppler recordings and the diastolic function due to confounding effects of preload and relaxation (7). Newer diastolic indexes that are less preload dependent include Ea velocity obtained from tissue Doppler and Vp obtained from color M-mode Doppler (11). The ability to use these newer indexes of diastolic function in patients with heart failure and abnormal preload would provide more objective information in the clinical setting. We go further by using the full spectrum of data presented in the color M-mode Doppler image by using a true quantitative approach to extract the pressure gradient from the velocity data in a noninvasive fashion.

In our study population, we clearly demonstrated the importance of LV relaxation as one of the determinants of O2 max. We showed that heart failure patients had a smaller augmentation in IVPG with exercise. Overall, the larger the delta IVPG, the higher the O2 achieved. The delta IVPG was the strongest predictor for the aerobic capacity as demonstrated in a multivariate linear regression model. This relationship held true after adjustments for ejection fraction and HR.

Interestingly, there was no significant difference in IVPG between patients and controls at rest, and one may speculate that normal subjects produce only enough diastolic suction force to serve their metabolic needs at any given time. Clearly, the ability to increase diastolic suction is a more important determinant of aerobic potential than baseline IVPG. As a check on our methodology, it should be noted that the baseline values of IVPG in our study population were similar to the ones observed invasively by others in resting patients with coronary heart disease (9).

Other determinants of the O2 max based on the stepwise regression model were baseline tissue Ea velocity and the baseline E/Vp ratio, again signifying the importance of a preserved LV relaxation and low filling pressures to have high aerobic exercise tolerance. Resting tissue Ea velocity may thus be a useful marker for the capability of the ventricle to enhance its IVPG with exercise. Similar findings that implicate diastolic function as a determining factor in exercise tolerance have been reported with the use of pulsed Doppler measurements (17, 41).

The noninvasively calculated KLV supported our findings in that the patients with heart failure have a stiffer heart with inability to relax and accept the large volume of blood in a shorter period of diastole at high HR (27, 30, 36). In both groups, the DT became shorter with exercise by ~20%. However, the increase in HR was significantly higher in the heart failure group. To reconcile this finding, one must realize that the HR has a weak effect on the DT (2).

During exercise, LV preload acutely increases, the HR rises with decrease in the timing of the diastolic stage, and the stroke volume increases; all of these physiological changes have one end result: increase in cardiac output (34). We demonstrated in this study that the cardiac output increased postexercise in both groups; however, in the heart failure group this response was blunted. Our study demonstrates that the normal ventricle has the ability to augment its relaxation potential and increase the suction of the blood from the LA. This adaptation may help to accommodate the increase in the filling rate at low filling pressures at a higher HR. It is interesting to note that in our population of normals, the resting HR was somewhat elevated, likely reflecting lack of physical fitness in this group. In patients with heart failure, this augmentation is diminished secondary to abnormal LV diastolic function (23, 29, 32, 35, 42), thus producing symptoms of dyspnea with exercise and providing for poor aerobic capacity. Kitzman and colleagues (22) demonstrated the importance of high pulmonary wedge pressures and exercise intolerance in patients with heart failure. Our data are similar to their results, although we used only noninvasive echocardiographic estimates.

The age difference between the two groups could in theory contribute to some of the results seen. As one gets older, the exercise capacity and the O2 max achieved do decrease; however, the derangements that were observed in the heart failure groups cannot be explained based on the age factor alone.

Limitations. Given the small size of our study population, further studies are needed to validate our conclusions. Our observed correlation between poor relaxation and low O2 max achieved as well as the negative correlation between increase in preload and ability to relax the ventricle reflect the true physiological state in patients with heart failure. However, we did not consider peripheral determinants of O2 max such as derangements in oxygen transport (20) or skeletal muscle deconditioning (19).

As expected, there was more variability in detecting the IVPG postexercise. Most of this variability comes from the increase in respiratory variation and increase in aliasing velocity noise that is present on the color M-mode image and is difficult to remove during analysis.

The critical assumption in obtaining the IVPG is that the M-mode scanline is aligned with the "true" velocities of the blood traveling into the LV through the mitral valve. Given the complex three-dimensional geometrical shape of the LV inflow, this assumption may not necessarily be true. However, Greenberg and colleagues (14) previously demonstrated using computer modeling that lateral displacement of the scan line by ±1.0 cm or angular misalignment by ±20° still resulted in an accurate reproduction of the pressure curve with r > 0.9.

A good quality color M-mode Doppler image is necessary in order for IVPG analysis to be valid. Sonographer expertise, changing the Nyquist limits to increase aliasing, and changing the baseline shift to provide a sharp border of the color map were important factors in optimizing the image quality. After exercise, the color M-mode Doppler data were acquired first so that the HR recovery was minimal.

The metabolic stress tests were performed on patients and normal subjects while they were standing, but the echocardiographic parameters of diastolic function were obtained in the supine position with their heads slightly elevated. Even though the LV preload is affected with positional changes, these effects are not very prominent in normal subjects (33). Patients with heart failure have a more profound effect on the ventricular preload when changing body position; however, when positioned with their head tilted upwards, ventricular filling indexes are minimally different from the upright position (43). Further studies using bicycle ergometers with echocardiographic capacity can be used to validate our findings.


   GRANTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
A. Rovner was supported by the Postdoctoral Fellowship Grant (0120418B) from the American Heart Association Ohio Valley Affiliate. This work was also supported in part by National Heart, Lung, and Blood Institute Grant 1-R01-HL-56688-01A1 and a grant from the National Space Biomedical Research Institute through National Aeronautics and Space Administration NCC 9-58.


   FOOTNOTES
 

Address for reprint requests and other correspondence: N. L. Greenberg, The Cleveland Clinic Foundation, 9500 Euclid Ave., Desk F15, Cleveland, OH 44195 (e-mail: greenbn{at}ccf.org)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
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 DISCUSSION
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 REFERENCES
 

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