© 2014, Wiley Periodicals, Inc. DOI: 10.1111/echo.12676
Echocardiography
The Effect of Age on Right Ventricular Diastolic Function in Healthy Subjects Undergoing Treadmill Exercise Test Murat Celik, M.D., Emre Yalcinkaya, M.D., Uygar Cagdas Yuksel, M.D., Yalcin Gokoglan, M.D., Baris Bugan, M.D., Hasan Kutsi Kabul, M.D., and Cem Barcin, M.D. Department of Cardiology, School of Medicine, Gulhane Military Medical Academy, Ankara, Turkey
Objective: There is an increasing interest for the value of right ventricle (RV) in predicting exercise tolerance and prognosis in cardiovascular disease. However, there is relatively few data evaluating the effect of age on RV diastolic filling velocities during rest or exercise in healthy subjects. Methods: A total of 54 healthy subjects were enrolled in this study. Patients were divided into 2 groups according to their age: Group 1 (≤45-years-old) and Group 2 (>45-years-old). A treadmill exercise test was performed using modified Bruce protocol. Conventional pulsed-wave Doppler and tissue Doppler velocities were obtained both at rest and immediately after the end of exercise, respectively. Results: In the overall analysis, tricuspid flow Doppler analysis showed a significant increase in A-wave velocity, less marked rise in E-wave velocity, decreased E/A ratio and decreased E-wave deceleration time (EDT) with exercise. Tissue Doppler analysis revealed increased Aa velocity, decreased in Ea/Aa ratio and IVRT. No significant change was observed in Ea velocity and E/Ea ratio with exercise. Although diastolic velocities changed significantly with exercise, systolic velocities did not. Cardiac response to exercise differed slightly in the older subjects compared to younger ones. The older subjects were more likely to have a reduced mean rate of RV filling for the second half of diastole from baseline to peak exercise. Conclusion: To distinguish normal physiological changes due to aging from those of pathologic conditions may provide benefits while evaluating patients with known or suspected cardiovascular disease. (Echocardiography 2015;32:436–442) Key words: healthy subjects, treadmill exercise test, right ventricle, aging, pulsed-wave Doppler, Doppler tissue imaging
There is increasing evidence for the importance of evaluating right ventricular (RV) function for risk stratification and prognosis.1 RV dysfunction has been shown to correlate with exercise intolerance in patients with heart failure.2 However, the contribution of RV dysfunction to the symptoms of heart failure cannot be fully elucidated mainly because of its structural and functional complexity.3 Despite RV systolic dysfunction has been shown to correlate with exercise intolerance in various diseases, particularly in heart failure, little is known about RV diastolic function. Age is a well-known determinant of global and regional right ventricular function, as well as left ventricle.4 Tissue and conventional Doppler echocardiography parameters evaluating RV diastolic performance varies with patient’s age.5 Address for correspondence and reprint requests: Murat Celik, M.D., Department of Cardiology, Gulhane Military Medical Academy, 06018 Etlik-Ankara. Turkey. Fax: + 90 312 304 42 50; E-mail: [email protected]
436
Exercise-induced changes in RV diastolic function can be an early and sensitive indicator of RV dysfunction.6 As heart failure is more common with increasing age, it is imperative to distinguish normal physiological changes related to aging from those of pathological processes resulting in cardiovascular diseases. Data regarding the effect of age on diastolic indices during rest and exercise in healthy subjects are scarce, and normal agerelated physiological changes can be misdiagnosed. In this study, we aimed to evaluate the effect of treadmill exercise test on tricuspid inflow and tissue Doppler velocity of tricuspid annulus in healthy people in different age groups. Material and Methods: Study Population: Subjects with normal physical and echocardiographic examination and negative treadmill stress test were enrolled in this study. Coronary artery disease, diabetes mellitus, hypertension, atrial fibrillation, tricuspid valve regurgitation
Right Ventricular Function and Treadmill Exercise Test
and/or stenosis, pulmonary hypertension, congenital heart defects, heart failure, and poor echocardiographic visualization were regarded as exclusion criteria. To analyze the effects of exercise on RV filling patterns in different age groups, the subjects were divided into 2 groups: Group 1 consisted of younger subjects with ≤45-years-old and Group 2 consisted of older subjects with >45-year-old. The study was carried out in accordance with the guidelines of the Declaration of Helsinki and Good Clinical Practice/International Conference on Harmonization and approved by the local institutional ethics committee. Echocardiography: Transthoracic echocardiography was performed using a Philips iE33 6.0 ultrasound system (Philips Medical Systems, Andover, MA, USA) with a 2.5 MHz transducer. At rest, standard 2-dimensional (2D) measurements, pulsed-wave Doppler evaluation of tricuspid flow at the level of the tips of fully open tricuspid leaflets and pulsed-wave tissue Doppler imaging with a 5 mm sample volume placed at the lateral margin of the tricuspid annulus in apical four-chamber view at the end of expiration were obtained according to the standard criteria. Tricuspid inflow early (E) and late (A) diastolic flow velocities, tricuspid E-wave deceleration time (EDT), tissue Doppler velocities of peak early (Ea) and late (Aa) diastolic tricuspid annular velocities, peak systolic tricuspid annular velocity (TASV) and isovolumic relaxation time (IVRT) were analyzed. Immediate postexercise echocardiography including tricuspid inflow parameters and tissue Doppler velocity of tricuspid annulus was performed within 2 minutes of peak exercise. We tried to get optimal images to accurate assessment immediately after exercise. Increased heart rate has often caused merging of early and late diastolic waves and might be a major problem to make appropriate echocardiographic analyses. We waited a reasonable time not exceeding 1 minute for the separation of the 2 waves. If these criteria were not met for analysis, that particular patient was classified as “not suitable” and excluded. Poor echocardiographic visualization due to motion and respiratory artifacts were regarded as exclusion criteria as well. All data were digitally stored and all analyses were performed off line by 2 separate investigators blinded to each other’s results and subjects’ clinical data. Average of 3 consecutive beats was used for analyses. Treadmill Exercise Test: Treadmill exercise testing was performed with a Maquette Treadmill System (Maquette
Electronics, Milwaukee, WI, USA) using modified Bruce protocol. The duration of the exercise, age-predicted maximum heart rate (APMHR), peak heart rate achieved (PHRA), and the metabolic equivalent (MET) levels were identified as according to the recommendations of the American College of Sports Medicine.7 Eighty-five percentage of age-predicted maximal heart rate was accepted as test endpoint. Statistical Analysis: The distribution characteristics of the data were tested using the Kolmogorov–Smirnov test. Continuous variables are presented as means standard deviation (SD) and the categorical variables as percentages. Chi-square test was used to compare categorical data. Independent-Samples t-test and Mann–Whitney U test were used to compare continuous variables with normal distributions and nonnormal distributions, respectively. Spearman’s and Pearson’s correlation coefficients were used to perform univariate correlation. The percentage change rate of RV Doppler parameters were calculated by dividing the difference between pre- and postexercise values to preexercise values and then multiplying by 100. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS, Chicago, IL, USA) version 20. P < 0.05 was considered statistically significant. Results: A total of 54 healthy subjects (27 male) aged 20–72 years (mean age 41.2 17.0 years) were enrolled in this study. The mean age of subjects was 26.3 5.5 years in group 1 and 57.3 7.7 years in group 2 (P < 0.001). The baseline demographic data, clinical characteristics, echocardiographic findings, and exercise test results of the study population are shown in Table I. The duration of exercise, APMHR and PHRA were significantly lower in the older group. The achievement of 85% of APMHR has been considered as adequately “stressed” and all subjects in this study met this criterion. Some authors suggest that 85% of APMHR is not a valid endpoint for exercise and using this criterion may lead to an underestimation of inducible ischemia. Although older subjects had lower exercise duration at similar PHRA level, all subjects enrolled in this study reached PHRA levels those were obviously higher than the 85% of APMHR (97.48 5.66% in group 1 and 96.70 8.58% in group 2, P = 0.754). In the overall evaluation of the study subjects, tricuspid flow showed a significant increase in A-wave velocity (P < 0.001), less marked rise in E-wave velocitiy (P = 0.037), decrease in E/A ratio (P < 0.001) and significant decrease in EDT 437
Celik, et al.
TABLE I Baseline Demographic and Clinical Data of Study Group
Demographics Age (years) Male, n (%) Smoke, n (%) Height (cm) Weight (kg) Body mass index (kg/m2) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Exercise test Duration (min) METs APMHR (bpm) PHRA (bpm) Percentage of APMHR, (%) Echocardiography LVIDd, (mm) IVSd, (mm) LVPWd, (mm) LA, (mm) Ao, (mm) LVEF, (%) RVD1, (mm) RVD2, (mm) RVD3, (mm) RA, (mm) RV FAC, (%) TAPSE, (mm)
Group 1 (≤45 Years) (n = 28)
Group 2 (>45 years) (n = 26)
P
26.3 5.5 15 (53.6%) 8 (28.6%) 171.5 8.3 69.1 12.2 23.4 3.2 116.8 11.9 74.8 8.6
57.3 7.7 12 (46.2%) 6 (23.1%) 165.7 6.6 71.6 11.5 26.1 4.0 129.0 13.7 78.3 7.9
Echocardiography
The Effect of Age on Right Ventricular Diastolic Function in Healthy Subjects Undergoing Treadmill Exercise Test Murat Celik, M.D., Emre Yalcinkaya, M.D., Uygar Cagdas Yuksel, M.D., Yalcin Gokoglan, M.D., Baris Bugan, M.D., Hasan Kutsi Kabul, M.D., and Cem Barcin, M.D. Department of Cardiology, School of Medicine, Gulhane Military Medical Academy, Ankara, Turkey
Objective: There is an increasing interest for the value of right ventricle (RV) in predicting exercise tolerance and prognosis in cardiovascular disease. However, there is relatively few data evaluating the effect of age on RV diastolic filling velocities during rest or exercise in healthy subjects. Methods: A total of 54 healthy subjects were enrolled in this study. Patients were divided into 2 groups according to their age: Group 1 (≤45-years-old) and Group 2 (>45-years-old). A treadmill exercise test was performed using modified Bruce protocol. Conventional pulsed-wave Doppler and tissue Doppler velocities were obtained both at rest and immediately after the end of exercise, respectively. Results: In the overall analysis, tricuspid flow Doppler analysis showed a significant increase in A-wave velocity, less marked rise in E-wave velocity, decreased E/A ratio and decreased E-wave deceleration time (EDT) with exercise. Tissue Doppler analysis revealed increased Aa velocity, decreased in Ea/Aa ratio and IVRT. No significant change was observed in Ea velocity and E/Ea ratio with exercise. Although diastolic velocities changed significantly with exercise, systolic velocities did not. Cardiac response to exercise differed slightly in the older subjects compared to younger ones. The older subjects were more likely to have a reduced mean rate of RV filling for the second half of diastole from baseline to peak exercise. Conclusion: To distinguish normal physiological changes due to aging from those of pathologic conditions may provide benefits while evaluating patients with known or suspected cardiovascular disease. (Echocardiography 2015;32:436–442) Key words: healthy subjects, treadmill exercise test, right ventricle, aging, pulsed-wave Doppler, Doppler tissue imaging
There is increasing evidence for the importance of evaluating right ventricular (RV) function for risk stratification and prognosis.1 RV dysfunction has been shown to correlate with exercise intolerance in patients with heart failure.2 However, the contribution of RV dysfunction to the symptoms of heart failure cannot be fully elucidated mainly because of its structural and functional complexity.3 Despite RV systolic dysfunction has been shown to correlate with exercise intolerance in various diseases, particularly in heart failure, little is known about RV diastolic function. Age is a well-known determinant of global and regional right ventricular function, as well as left ventricle.4 Tissue and conventional Doppler echocardiography parameters evaluating RV diastolic performance varies with patient’s age.5 Address for correspondence and reprint requests: Murat Celik, M.D., Department of Cardiology, Gulhane Military Medical Academy, 06018 Etlik-Ankara. Turkey. Fax: + 90 312 304 42 50; E-mail: [email protected]
436
Exercise-induced changes in RV diastolic function can be an early and sensitive indicator of RV dysfunction.6 As heart failure is more common with increasing age, it is imperative to distinguish normal physiological changes related to aging from those of pathological processes resulting in cardiovascular diseases. Data regarding the effect of age on diastolic indices during rest and exercise in healthy subjects are scarce, and normal agerelated physiological changes can be misdiagnosed. In this study, we aimed to evaluate the effect of treadmill exercise test on tricuspid inflow and tissue Doppler velocity of tricuspid annulus in healthy people in different age groups. Material and Methods: Study Population: Subjects with normal physical and echocardiographic examination and negative treadmill stress test were enrolled in this study. Coronary artery disease, diabetes mellitus, hypertension, atrial fibrillation, tricuspid valve regurgitation
Right Ventricular Function and Treadmill Exercise Test
and/or stenosis, pulmonary hypertension, congenital heart defects, heart failure, and poor echocardiographic visualization were regarded as exclusion criteria. To analyze the effects of exercise on RV filling patterns in different age groups, the subjects were divided into 2 groups: Group 1 consisted of younger subjects with ≤45-years-old and Group 2 consisted of older subjects with >45-year-old. The study was carried out in accordance with the guidelines of the Declaration of Helsinki and Good Clinical Practice/International Conference on Harmonization and approved by the local institutional ethics committee. Echocardiography: Transthoracic echocardiography was performed using a Philips iE33 6.0 ultrasound system (Philips Medical Systems, Andover, MA, USA) with a 2.5 MHz transducer. At rest, standard 2-dimensional (2D) measurements, pulsed-wave Doppler evaluation of tricuspid flow at the level of the tips of fully open tricuspid leaflets and pulsed-wave tissue Doppler imaging with a 5 mm sample volume placed at the lateral margin of the tricuspid annulus in apical four-chamber view at the end of expiration were obtained according to the standard criteria. Tricuspid inflow early (E) and late (A) diastolic flow velocities, tricuspid E-wave deceleration time (EDT), tissue Doppler velocities of peak early (Ea) and late (Aa) diastolic tricuspid annular velocities, peak systolic tricuspid annular velocity (TASV) and isovolumic relaxation time (IVRT) were analyzed. Immediate postexercise echocardiography including tricuspid inflow parameters and tissue Doppler velocity of tricuspid annulus was performed within 2 minutes of peak exercise. We tried to get optimal images to accurate assessment immediately after exercise. Increased heart rate has often caused merging of early and late diastolic waves and might be a major problem to make appropriate echocardiographic analyses. We waited a reasonable time not exceeding 1 minute for the separation of the 2 waves. If these criteria were not met for analysis, that particular patient was classified as “not suitable” and excluded. Poor echocardiographic visualization due to motion and respiratory artifacts were regarded as exclusion criteria as well. All data were digitally stored and all analyses were performed off line by 2 separate investigators blinded to each other’s results and subjects’ clinical data. Average of 3 consecutive beats was used for analyses. Treadmill Exercise Test: Treadmill exercise testing was performed with a Maquette Treadmill System (Maquette
Electronics, Milwaukee, WI, USA) using modified Bruce protocol. The duration of the exercise, age-predicted maximum heart rate (APMHR), peak heart rate achieved (PHRA), and the metabolic equivalent (MET) levels were identified as according to the recommendations of the American College of Sports Medicine.7 Eighty-five percentage of age-predicted maximal heart rate was accepted as test endpoint. Statistical Analysis: The distribution characteristics of the data were tested using the Kolmogorov–Smirnov test. Continuous variables are presented as means standard deviation (SD) and the categorical variables as percentages. Chi-square test was used to compare categorical data. Independent-Samples t-test and Mann–Whitney U test were used to compare continuous variables with normal distributions and nonnormal distributions, respectively. Spearman’s and Pearson’s correlation coefficients were used to perform univariate correlation. The percentage change rate of RV Doppler parameters were calculated by dividing the difference between pre- and postexercise values to preexercise values and then multiplying by 100. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS, Chicago, IL, USA) version 20. P < 0.05 was considered statistically significant. Results: A total of 54 healthy subjects (27 male) aged 20–72 years (mean age 41.2 17.0 years) were enrolled in this study. The mean age of subjects was 26.3 5.5 years in group 1 and 57.3 7.7 years in group 2 (P < 0.001). The baseline demographic data, clinical characteristics, echocardiographic findings, and exercise test results of the study population are shown in Table I. The duration of exercise, APMHR and PHRA were significantly lower in the older group. The achievement of 85% of APMHR has been considered as adequately “stressed” and all subjects in this study met this criterion. Some authors suggest that 85% of APMHR is not a valid endpoint for exercise and using this criterion may lead to an underestimation of inducible ischemia. Although older subjects had lower exercise duration at similar PHRA level, all subjects enrolled in this study reached PHRA levels those were obviously higher than the 85% of APMHR (97.48 5.66% in group 1 and 96.70 8.58% in group 2, P = 0.754). In the overall evaluation of the study subjects, tricuspid flow showed a significant increase in A-wave velocity (P < 0.001), less marked rise in E-wave velocitiy (P = 0.037), decrease in E/A ratio (P < 0.001) and significant decrease in EDT 437
Celik, et al.
TABLE I Baseline Demographic and Clinical Data of Study Group
Demographics Age (years) Male, n (%) Smoke, n (%) Height (cm) Weight (kg) Body mass index (kg/m2) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Exercise test Duration (min) METs APMHR (bpm) PHRA (bpm) Percentage of APMHR, (%) Echocardiography LVIDd, (mm) IVSd, (mm) LVPWd, (mm) LA, (mm) Ao, (mm) LVEF, (%) RVD1, (mm) RVD2, (mm) RVD3, (mm) RA, (mm) RV FAC, (%) TAPSE, (mm)
Group 1 (≤45 Years) (n = 28)
Group 2 (>45 years) (n = 26)
P
26.3 5.5 15 (53.6%) 8 (28.6%) 171.5 8.3 69.1 12.2 23.4 3.2 116.8 11.9 74.8 8.6
57.3 7.7 12 (46.2%) 6 (23.1%) 165.7 6.6 71.6 11.5 26.1 4.0 129.0 13.7 78.3 7.9
