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Estimation of Left Ventricular Filling Pressure with Exercise by Doppler Echocardiography in Patients with Normal Systolic Function: A Simultaneous Echocardiographic–Cardiac Catheterization Study
Estimation of Left Ventricular Filling Pressure with Exercise by Doppler Echocardiography in Patients with Normal Systolic Function: A Simultaneous Echocardiographic–Cardiac Catheterization Study Deepak R. Talreja, MD, Rick A. Nishimura, MD, and Jae K. Oh, MD, Virginia Beach, Virginia, and Rochester, Minnesota
Background: Doppler echocardiography is now used to evaluate left ventricular filling pressures in patients at rest. However, the clinical use of Doppler echocardiography in the determination of filling pressures with exercise has been less well studied. Objective: The aim of this prospective study was to confirm the validity of an accepted Doppler parameter (ratio of transmitral E velocity to Doppler tissue annular e’ velocity [E/e’]) as a measure of filling pressure in patients with normal systolic function during rest and exercise. Methods: Twelve patients who presented with symptoms of dyspnea and ejection fraction greater than 50% underwent an exercise right heart catheterization during a symptom-limited bicycle exercise test. Simultaneous Doppler assessment of transmitral flow and tissue Doppler annulus motion was recorded.
It is essential to determine left ventricular (LV)
filling pressures in patients with known or suggested cardiac disease, as diastolic function plays an integral role in the pathophysiology of cardiac symptoms.1,2 Noninvasive Doppler techniques are now used to assess LV filling pressures at rest1,3-5 and there is growing evidence to show that these same parameters can be used to measure changes in filling pressures, which may occur with exercise.6 This is of particular importance in patients presenting with exertional symptoms with no known structural heart disease, in whom the cause of the symptoms From the Sentara Virginia Beach General Hospital/Eastern Virginia Medical School (D.R.T.), and Division of Cardiovascular Diseases, Mayo Clinic College of Medicine. Supported by a postdoctoral fellowship grant from the American Heart Association. Reprint requests: Rick A. Nishimura, MD, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (E-mail: [email protected]). 0894-7317/$32.00 Copyright 2007 by the American Society of Echocardiography. doi:10.1016/j.echo.2006.10.005
Results: The transmitral E velocity increased from 0.88 ⴞ 0.2 to 1.29 ⴞ 0.4 cm/s whereas the mitral annular e’ velocity increased from 0.08 ⴞ 0.02 to 0.11 ⴞ 0.06 with exercise. The E/e’ ratio increased from 11.7 ⴞ 0.5 to 14.4 ⴞ 0.6. Pulmonary artery wedge pressure (PAWP) increased from 14 ⴞ 4 to 23 ⴞ 10 mm Hg at peak exercise. The sensitivity of an E/e’ of 15 or less as a predictor for a normal PAWP during exercise was 89%. Conversely, in all cases where the E/e’ was greater than 15, the PAWP was elevated during exercise. Conclusion: Noninvasively obtained Doppler of mitral and mitral annulus velocities provides a reliable estimation of PAWP not only at baseline, but also with exercise. Specifically, an E/e’ ratio of greater than 15 during exercise is associated with a significantly elevated PAWP of greater than 20 mm Hg. (J Am Soc Echocardiogr 2007;20:477-479.)
may be unclear. The aim of this prospective study was to confirm the validity of on accepted Doppler parameter (ratio of transmitral E velocity to Doppler tissue annular e’ velocity [E/e’]) as a measure of filling pressure not only at rest, but also with exercise. We specifically studied patients with normal systolic function and no other known cardiac disease, correlating the Doppler findings with simultaneously determined pulmonary artery wedge pressure (PAWP) in the cardiac catheterization laboratory.
METHODS From May 2002 through June 2004, 12 patients with ejection fraction greater than 50% and exertional dyspnea (New York Heart Association class II-III) were prospectively recruited. The inclusion criteria were: (1) age 40 years or older; (2) clinically indicated right heart catheterization; and (3) LV ejection fraction greater than 50%. The exclusion criteria were: (1) more than moderate valvular heart disease or a mitral prosthesis; (2) chronic obstruc-
477
Journal of the American Society of Echocardiography May 2007
478 Talreja, Nishimura, Oh
Table Echocardiographic data and pulmonary capillary wedge pressure measured at baseline and peak exercise Baseline
Blood pressure, mm Hg Heart rate, beats/min E velocity, m/s e’ velocity, m/s E/e’ velocity Deceleration time, ms PAWP
140 68 0.84 0.08 11.7 202 14
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
18 10 0.2 0.02 0.5 40 4
Peak exercise
179 117 1.25 0.10 14.5 181 22
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
20 30 0.4 0.06 0.6 29 10
P values
P P P P P P P
⬍ ⬍ ⬍ ⬍ ⬍ ⬍ ⬍
.0001 .0001 .0007 .08 .0016 .006 .001
E, Transmitral initial peak diastolic velocity; e’, Doppler tissue annular initial peak diastolic velocity.
tive lung disease (forced expiratory volume in 1 second ⬍ 70% predicted); and (3) known or suggested primary pulmonary hypertension or pulmonary embolism. These patients were specifically sent to the catheterization laboratory to determine the cause of exertional dyspnea after a full evaluation revealed no confirmed origin of the symptoms. The study protocol was approved by our institutional review board. The study population consisted of 10 women and 2 men with a mean age of 58 ⫾ 9 years. Their mean ejection fraction was 66 ⫾ 5%. All patients of the study underwent a symptom-limited exercise test on a supine bicycle with right heart catheterization performed from the internal jugular access. Rest measurements were taken after equilibration of the feet up in the bicycle stirrups for 3 minutes. The exercise protocol consisted of pedaling at 60 to 80 rpm for an initial workload of 25 W, increasing by 25 W every 3 minutes until the patient became symptomatic. A simultaneous transthoracic echocardiogram was performed with transmitral Doppler and Doppler tissue imaging of the medial annulus as previously described.3,4 At each stage blood pressure, heart rate, pulmonary artery pressure, PAWP, transmitral Doppler E velocity, deceleration time, and tissue Doppler annular velocity (e’) were recorded.
RESULTS The clinical, echocardiographic, and catheterization parameters are summarized in Table. The transmitral E velocity increased from 0.88 ⫾ 0.2 to 1.29 ⫾ 0.4 cm/s whereas the mitral annular e’ velocity increased from 0.08 ⫾ 0.02 to 0.11 ⫾ 0.06 with exercise. The E/e’ ratio increased from 11.7 ⫾ 0.5 to 14.4 ⫾ 0.6. The PAWP increased from 14 ⫾ 4 to 23 ⫾ 10 mm Hg at peak exercise. The noninvasively derived E/e’ versus PAWP for all patients at baseline and peak exercise measurements is shown in Figure. Based on the invasive hemodynamic data, the diastolic function was classified as normal (PAWP ⱕ 20 mm Hg) or abnormal (PAWP ⬎ 20 mm Hg). The sensitivity of an E/e’ of 15
Figure Plot of pulmonary capillary wedge pressure (PCWP) versus E/e’ with baseline and peak exercise values for each patient.
or less as a predictor for a normal PAWP was 89%. Conversely, in all cases where the E/e’ was greater than 15, the PAWP was elevated. At baseline, E/e’ was 15 or less in 10 patients and greater than 15 in 2 patients. Of 10 patients who had E/e’ less than or equal to baseline, E/e’ remained 15 or less in 7 patients and increased to greater than 15 in 3 patients. All patients who had an E/e’ greater than 15 during exercise developed an elevated PAWP greater than 20 mm Hg. E/e’ remained greater than 15 with exercise in the two patients who had an elevated E/e’ at baseline. In these two patients, PAWP was greater than 20 mm Hg at baseline and increased with exercise.
DISCUSSION Patients with normal systolic function and hypertension or LV hypertrophy may have limiting symptoms of dyspnea with exertion as a result of diastolic dysfunction.7-9 Their diastolic filling can be compensated in the baseline state, without rest symptoms. However, during exercise, they are unable to increase cardiac output without an abnormal elevation in left atrial pressure because of the inability of the LV to enhance its diastolic filling. Invasive catheterization studies have demonstrated an increase in PAWP in patients with a history of heart failure with normal systolic function, confirming the existence of exercise-induced diastolic dysfunction.10 Up until recently, however, an invasive approach was required to determine LV filling abnormalities at rest and exercise.10,11 For widespread clinical application, a less invasive surrogate that correlates well to these invasive hemodynamic parameters is necessary to assess the diastolic functional reserve capacity. In this study, we have shown that noninvasively obtained Doppler of mitral and mitral annulus velocities provides a reliable estimation of PAWP not only
Journal of the American Society of Echocardiography Volume 20 Number 5
at baseline, but also with exercise. Specifically, an E/e’ ratio of greater than 15 during exercise was associated with a significantly elevated PAWP of greater than 20 mm Hg. This finding is consistent with prior studies that examined simultaneous correlation of Doppler and invasive filling pressures in the resting state,3-5,12 but now extends the correlation to its use during exercise. The results of this study add to our understanding of the use of noninvasive Doppler evaluation of filling pressures during exercise. Our group has previously shown that both the transmitral E velocity and the Doppler tissue e’ increases but the E/e’ ratio does not change during exercise in healthy individuals without known heart disease.13 This is consistent with our understanding of the normal physiologic response to exercise with a faster myocardial relaxation rate (evidenced by an increase in e’ velocity) causing an exaggerated suction effect of the LV (shown by a higher transmitral E velocity). This allows the left atrium to fully empty because the early diastolic portion of the LV pressure-volume curve is shifted downward, increasing early diastolic filling without an increase in filling pressure. Patients who were referred with symptoms of dyspnea and a limited exercise tolerance had an increase in E/e’ ratio with exercise.14 In these patients, it was postulated that ventricular filling was impaired as a result of the lack of the suction effect. Thus, an elevated left atrial pressure must be tolerated to increase cardiac output to meet the demands of the body during exercise. The definitive confirmation of using these noninvasive techniques for assessment of filling pressures requires correlation with invasive pressure measurements, as was done in this study. Burgess et al6 recently showed a similar correlation of the ratio of E/e’ and LV diastolic pressure during exercise. They used a submaximal single leg exercise and had a more heterogeneous population (75% had concomitant coronary artery disease and the systolic function was variable). Our protocol used a symptomlimited bicycle exercise protocol and consisted of a very select group of patients with normal systolic function who were specifically referred to the catheterization laboratory to determine the cause of exertional dyspnea. Nonetheless, the findings of an elevated E/e’ with exercise indicating an elevation of filling pressures was found in both studies and supports the clinical use of these Doppler parameters during exercise. There are limitations to this study. Our patient population was small but highly selected and does represent the group of patients who pose the greatest diagnostic dilemma to the clinician. We only used patients in sinus rhythm and it is not known whether this can be applied to patients with other rhythms such as atrial fibrillation. The number of
Talreja, Nishimura, Oh 479
patients was too small to provide analysis of receiver operator curves or true predictive value of certain parameters. This was an initial study to determine the feasibility of the hypothesis that filling pressures can be determined noninvasively during exercise. Further studies with larger numbers of patients will be required to determine whether this methodology can be applied to larger groups of patients with different disease entities and to determine clinically relevant values that can be applied in clinical practice. REFERENCES 1. Oh JK, Hatle L, Tajik AJ, Little WC. Diastolic heart failure can be diagnosed by comprehensive two-dimensional and Doppler echocardiography. J Am Coll Cardiol 2006;47:500-6. 2. Nishimura RA, Tajik AJ. Evaluation of diastolic filling of left ventricle in health and disease: Doppler echocardiography is the clinician’s Rosetta stone. J Am Coll Cardiol 1997;30:8-18. 3. Ommen SR, Nishimura RA. A clinical approach to the assessment of left ventricular diastolic function by Doppler echocardiography: update 2003. Heart 2003;89:iii18-23. 4. Ommen SR, Nishimura RA, Appleton CP, et al. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation 2000;102:1788-94. 5. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol 1997;30:1527-33. 6. Burgess MI, Jenkins C, Sharman JE, Marwick TH. Diastolic stress echocardiography: hemodynamic validation and clinical significance of estimation of ventricular filling pressures with exercise. J Am Coll Cardiol 2006;47:1891-900. 7. Vasan RS, Benjamin EJ, Levy D. Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol 1995;26:1565-74. 8. Nishimura RA, Housmans PR, Hatle LK, Tajik AJ. Assessment of diastolic function of the heart: background and current applications of Doppler echocardiography, part I–physiologic and pathophysiologic features. Mayo Clin Proc 1989;64:71-81. 9. Packer M. Abnormalities of diastolic function as a potential cause of exercise intolerance in chronic heart failure. Circulation 1990;81:III78-86. 10. Kitzman DW, Higginbotham MB, Cobb FR, Sheikh KH, Sullivan MJ. Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the FrankStarling mechanism. J Am Coll Cardiol 1991;17:1065-72. 11. Kass DA. Assessment of diastolic dysfunction: invasive modalities. Cardiol Clin 2000;18:571-86. 12. Nagueh SF, Sun H, Kopelen HA, Middleton KJ, Khoury DS. Hemodynamic determinants of the mitral annulus diastolic velocities by tissue Doppler. J Am Coll Cardiol 2001;37:278-85. 13. Ha JW, Lulic F, Bailey KR, et al. Effects of treadmill exercise on mitral inflow and annular velocities in healthy adults. Am J Cardiol 2003;91:114-5. 14. Ha JW, Oh JK, Pellikka PA, et al. Diastolic stress echocardiography: a novel noninvasive diagnostic test for diastolic dysfunction using supine bicycle exercise Doppler echocardiography. J Am Soc Echocardiogr 2005;18:63-8.
Background: Doppler echocardiography is now used to evaluate left ventricular filling pressures in patients at rest. However, the clinical use of Doppler echocardiography in the determination of filling pressures with exercise has been less well studied. Objective: The aim of this prospective study was to confirm the validity of an accepted Doppler parameter (ratio of transmitral E velocity to Doppler tissue annular e’ velocity [E/e’]) as a measure of filling pressure in patients with normal systolic function during rest and exercise. Methods: Twelve patients who presented with symptoms of dyspnea and ejection fraction greater than 50% underwent an exercise right heart catheterization during a symptom-limited bicycle exercise test. Simultaneous Doppler assessment of transmitral flow and tissue Doppler annulus motion was recorded.
It is essential to determine left ventricular (LV)
filling pressures in patients with known or suggested cardiac disease, as diastolic function plays an integral role in the pathophysiology of cardiac symptoms.1,2 Noninvasive Doppler techniques are now used to assess LV filling pressures at rest1,3-5 and there is growing evidence to show that these same parameters can be used to measure changes in filling pressures, which may occur with exercise.6 This is of particular importance in patients presenting with exertional symptoms with no known structural heart disease, in whom the cause of the symptoms From the Sentara Virginia Beach General Hospital/Eastern Virginia Medical School (D.R.T.), and Division of Cardiovascular Diseases, Mayo Clinic College of Medicine. Supported by a postdoctoral fellowship grant from the American Heart Association. Reprint requests: Rick A. Nishimura, MD, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (E-mail: [email protected]). 0894-7317/$32.00 Copyright 2007 by the American Society of Echocardiography. doi:10.1016/j.echo.2006.10.005
Results: The transmitral E velocity increased from 0.88 ⴞ 0.2 to 1.29 ⴞ 0.4 cm/s whereas the mitral annular e’ velocity increased from 0.08 ⴞ 0.02 to 0.11 ⴞ 0.06 with exercise. The E/e’ ratio increased from 11.7 ⴞ 0.5 to 14.4 ⴞ 0.6. Pulmonary artery wedge pressure (PAWP) increased from 14 ⴞ 4 to 23 ⴞ 10 mm Hg at peak exercise. The sensitivity of an E/e’ of 15 or less as a predictor for a normal PAWP during exercise was 89%. Conversely, in all cases where the E/e’ was greater than 15, the PAWP was elevated during exercise. Conclusion: Noninvasively obtained Doppler of mitral and mitral annulus velocities provides a reliable estimation of PAWP not only at baseline, but also with exercise. Specifically, an E/e’ ratio of greater than 15 during exercise is associated with a significantly elevated PAWP of greater than 20 mm Hg. (J Am Soc Echocardiogr 2007;20:477-479.)
may be unclear. The aim of this prospective study was to confirm the validity of on accepted Doppler parameter (ratio of transmitral E velocity to Doppler tissue annular e’ velocity [E/e’]) as a measure of filling pressure not only at rest, but also with exercise. We specifically studied patients with normal systolic function and no other known cardiac disease, correlating the Doppler findings with simultaneously determined pulmonary artery wedge pressure (PAWP) in the cardiac catheterization laboratory.
METHODS From May 2002 through June 2004, 12 patients with ejection fraction greater than 50% and exertional dyspnea (New York Heart Association class II-III) were prospectively recruited. The inclusion criteria were: (1) age 40 years or older; (2) clinically indicated right heart catheterization; and (3) LV ejection fraction greater than 50%. The exclusion criteria were: (1) more than moderate valvular heart disease or a mitral prosthesis; (2) chronic obstruc-
477
Journal of the American Society of Echocardiography May 2007
478 Talreja, Nishimura, Oh
Table Echocardiographic data and pulmonary capillary wedge pressure measured at baseline and peak exercise Baseline
Blood pressure, mm Hg Heart rate, beats/min E velocity, m/s e’ velocity, m/s E/e’ velocity Deceleration time, ms PAWP
140 68 0.84 0.08 11.7 202 14
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
18 10 0.2 0.02 0.5 40 4
Peak exercise
179 117 1.25 0.10 14.5 181 22
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
20 30 0.4 0.06 0.6 29 10
P values
P P P P P P P
⬍ ⬍ ⬍ ⬍ ⬍ ⬍ ⬍
.0001 .0001 .0007 .08 .0016 .006 .001
E, Transmitral initial peak diastolic velocity; e’, Doppler tissue annular initial peak diastolic velocity.
tive lung disease (forced expiratory volume in 1 second ⬍ 70% predicted); and (3) known or suggested primary pulmonary hypertension or pulmonary embolism. These patients were specifically sent to the catheterization laboratory to determine the cause of exertional dyspnea after a full evaluation revealed no confirmed origin of the symptoms. The study protocol was approved by our institutional review board. The study population consisted of 10 women and 2 men with a mean age of 58 ⫾ 9 years. Their mean ejection fraction was 66 ⫾ 5%. All patients of the study underwent a symptom-limited exercise test on a supine bicycle with right heart catheterization performed from the internal jugular access. Rest measurements were taken after equilibration of the feet up in the bicycle stirrups for 3 minutes. The exercise protocol consisted of pedaling at 60 to 80 rpm for an initial workload of 25 W, increasing by 25 W every 3 minutes until the patient became symptomatic. A simultaneous transthoracic echocardiogram was performed with transmitral Doppler and Doppler tissue imaging of the medial annulus as previously described.3,4 At each stage blood pressure, heart rate, pulmonary artery pressure, PAWP, transmitral Doppler E velocity, deceleration time, and tissue Doppler annular velocity (e’) were recorded.
RESULTS The clinical, echocardiographic, and catheterization parameters are summarized in Table. The transmitral E velocity increased from 0.88 ⫾ 0.2 to 1.29 ⫾ 0.4 cm/s whereas the mitral annular e’ velocity increased from 0.08 ⫾ 0.02 to 0.11 ⫾ 0.06 with exercise. The E/e’ ratio increased from 11.7 ⫾ 0.5 to 14.4 ⫾ 0.6. The PAWP increased from 14 ⫾ 4 to 23 ⫾ 10 mm Hg at peak exercise. The noninvasively derived E/e’ versus PAWP for all patients at baseline and peak exercise measurements is shown in Figure. Based on the invasive hemodynamic data, the diastolic function was classified as normal (PAWP ⱕ 20 mm Hg) or abnormal (PAWP ⬎ 20 mm Hg). The sensitivity of an E/e’ of 15
Figure Plot of pulmonary capillary wedge pressure (PCWP) versus E/e’ with baseline and peak exercise values for each patient.
or less as a predictor for a normal PAWP was 89%. Conversely, in all cases where the E/e’ was greater than 15, the PAWP was elevated. At baseline, E/e’ was 15 or less in 10 patients and greater than 15 in 2 patients. Of 10 patients who had E/e’ less than or equal to baseline, E/e’ remained 15 or less in 7 patients and increased to greater than 15 in 3 patients. All patients who had an E/e’ greater than 15 during exercise developed an elevated PAWP greater than 20 mm Hg. E/e’ remained greater than 15 with exercise in the two patients who had an elevated E/e’ at baseline. In these two patients, PAWP was greater than 20 mm Hg at baseline and increased with exercise.
DISCUSSION Patients with normal systolic function and hypertension or LV hypertrophy may have limiting symptoms of dyspnea with exertion as a result of diastolic dysfunction.7-9 Their diastolic filling can be compensated in the baseline state, without rest symptoms. However, during exercise, they are unable to increase cardiac output without an abnormal elevation in left atrial pressure because of the inability of the LV to enhance its diastolic filling. Invasive catheterization studies have demonstrated an increase in PAWP in patients with a history of heart failure with normal systolic function, confirming the existence of exercise-induced diastolic dysfunction.10 Up until recently, however, an invasive approach was required to determine LV filling abnormalities at rest and exercise.10,11 For widespread clinical application, a less invasive surrogate that correlates well to these invasive hemodynamic parameters is necessary to assess the diastolic functional reserve capacity. In this study, we have shown that noninvasively obtained Doppler of mitral and mitral annulus velocities provides a reliable estimation of PAWP not only
Journal of the American Society of Echocardiography Volume 20 Number 5
at baseline, but also with exercise. Specifically, an E/e’ ratio of greater than 15 during exercise was associated with a significantly elevated PAWP of greater than 20 mm Hg. This finding is consistent with prior studies that examined simultaneous correlation of Doppler and invasive filling pressures in the resting state,3-5,12 but now extends the correlation to its use during exercise. The results of this study add to our understanding of the use of noninvasive Doppler evaluation of filling pressures during exercise. Our group has previously shown that both the transmitral E velocity and the Doppler tissue e’ increases but the E/e’ ratio does not change during exercise in healthy individuals without known heart disease.13 This is consistent with our understanding of the normal physiologic response to exercise with a faster myocardial relaxation rate (evidenced by an increase in e’ velocity) causing an exaggerated suction effect of the LV (shown by a higher transmitral E velocity). This allows the left atrium to fully empty because the early diastolic portion of the LV pressure-volume curve is shifted downward, increasing early diastolic filling without an increase in filling pressure. Patients who were referred with symptoms of dyspnea and a limited exercise tolerance had an increase in E/e’ ratio with exercise.14 In these patients, it was postulated that ventricular filling was impaired as a result of the lack of the suction effect. Thus, an elevated left atrial pressure must be tolerated to increase cardiac output to meet the demands of the body during exercise. The definitive confirmation of using these noninvasive techniques for assessment of filling pressures requires correlation with invasive pressure measurements, as was done in this study. Burgess et al6 recently showed a similar correlation of the ratio of E/e’ and LV diastolic pressure during exercise. They used a submaximal single leg exercise and had a more heterogeneous population (75% had concomitant coronary artery disease and the systolic function was variable). Our protocol used a symptomlimited bicycle exercise protocol and consisted of a very select group of patients with normal systolic function who were specifically referred to the catheterization laboratory to determine the cause of exertional dyspnea. Nonetheless, the findings of an elevated E/e’ with exercise indicating an elevation of filling pressures was found in both studies and supports the clinical use of these Doppler parameters during exercise. There are limitations to this study. Our patient population was small but highly selected and does represent the group of patients who pose the greatest diagnostic dilemma to the clinician. We only used patients in sinus rhythm and it is not known whether this can be applied to patients with other rhythms such as atrial fibrillation. The number of
Talreja, Nishimura, Oh 479
patients was too small to provide analysis of receiver operator curves or true predictive value of certain parameters. This was an initial study to determine the feasibility of the hypothesis that filling pressures can be determined noninvasively during exercise. Further studies with larger numbers of patients will be required to determine whether this methodology can be applied to larger groups of patients with different disease entities and to determine clinically relevant values that can be applied in clinical practice. REFERENCES 1. Oh JK, Hatle L, Tajik AJ, Little WC. Diastolic heart failure can be diagnosed by comprehensive two-dimensional and Doppler echocardiography. J Am Coll Cardiol 2006;47:500-6. 2. Nishimura RA, Tajik AJ. Evaluation of diastolic filling of left ventricle in health and disease: Doppler echocardiography is the clinician’s Rosetta stone. J Am Coll Cardiol 1997;30:8-18. 3. Ommen SR, Nishimura RA. A clinical approach to the assessment of left ventricular diastolic function by Doppler echocardiography: update 2003. Heart 2003;89:iii18-23. 4. Ommen SR, Nishimura RA, Appleton CP, et al. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation 2000;102:1788-94. 5. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol 1997;30:1527-33. 6. Burgess MI, Jenkins C, Sharman JE, Marwick TH. Diastolic stress echocardiography: hemodynamic validation and clinical significance of estimation of ventricular filling pressures with exercise. J Am Coll Cardiol 2006;47:1891-900. 7. Vasan RS, Benjamin EJ, Levy D. Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol 1995;26:1565-74. 8. Nishimura RA, Housmans PR, Hatle LK, Tajik AJ. Assessment of diastolic function of the heart: background and current applications of Doppler echocardiography, part I–physiologic and pathophysiologic features. Mayo Clin Proc 1989;64:71-81. 9. Packer M. Abnormalities of diastolic function as a potential cause of exercise intolerance in chronic heart failure. Circulation 1990;81:III78-86. 10. Kitzman DW, Higginbotham MB, Cobb FR, Sheikh KH, Sullivan MJ. Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the FrankStarling mechanism. J Am Coll Cardiol 1991;17:1065-72. 11. Kass DA. Assessment of diastolic dysfunction: invasive modalities. Cardiol Clin 2000;18:571-86. 12. Nagueh SF, Sun H, Kopelen HA, Middleton KJ, Khoury DS. Hemodynamic determinants of the mitral annulus diastolic velocities by tissue Doppler. J Am Coll Cardiol 2001;37:278-85. 13. Ha JW, Lulic F, Bailey KR, et al. Effects of treadmill exercise on mitral inflow and annular velocities in healthy adults. Am J Cardiol 2003;91:114-5. 14. Ha JW, Oh JK, Pellikka PA, et al. Diastolic stress echocardiography: a novel noninvasive diagnostic test for diastolic dysfunction using supine bicycle exercise Doppler echocardiography. J Am Soc Echocardiogr 2005;18:63-8.