1540 JACC Vol. 13, No. 7 June 1989:1540-5

Pulsed and Continuous Wave Doppler Echocardiographic Assessment of Valvular Regurgitation in Normal Subjects

MARVIN BERGER, MD, FACC, SUSAN R. HECHT, MD, FACC, ANDREW VAN TOSH, MD, FACC, UMADEVI LINGAM, BS New York, New York

To assess the prevalence and flow characteristics of valvular regurgitation detected by Doppler echocardiography in normal subjects, pulsed and continuous wave Doppler studies were performed in 100 adult volunteers without evidence of heart disease. Evidence of valvular regurgita- tion was present in 73% of subjects. There were 46 subjects with regurgitation of one valve, 24 with regurgitation of two valves and 3 with regurgitation of three valves. Right-sided regurgitation was significantly more common than was left-sided regurgitation (81 versus 22 valves, p < 0.01). Regurgitant flow was never detected farther than 1 cm from the valve by pulsed Doppler study.

Tricuspid regurgitation was detected in 50 subjects and was characterized by a halosystolic velocity signal; a com- plete spectral envelope was recorded in 32 subjects. The peak velocity of the regurgitant jet for this group was 1.7 to 2.3 m/s (mean 2.0 f 0.2). Thirty-one subjects were found to

Doppler echocardiography is currently the most reliable noninvasive technique for diagnosing valvular regurgitation and is comparable in sensitivity and specificity to cineangi- ography (l-8). Recent studies (5,9-12) have also shown it to be more sensitive than cardiac auscultation, particularly in those cases where valvular regurgitation is mild. Somewhat unexpected has been the observation that Doppler echocar- diography can frequently detect mild degrees of valvular regurgitation in normal subjects (12-14). This finding has been a matter of great concern to echocardiographers be- cause no standard method exists for reporting these findings. Although reports describing valvular regurgitation in normal subjects have appeared (13-B), the study groups have been

From the Division of Cardiology, Department of Medicine. Beth Israel Medical Center, New York, New York and the Department of Medicine, the Mount Sinai School of Medicine of the City University of New York, New York.

Manuscript received August 1, 1988; revised manuscript received Decem- ber 13, 1988, accepted January 6, 1989.

Address: Marvin Berger, MD, Beth Israel Medical Center, First Avenue at 16th Street, New York, New York 10003.

have pulmonary regurgitation with a peak velocity of 1.2 to 1.9 m/s (mean 1.5 f 0.2); no subject demonstrated regur- gitant flow in early diastole. There were 21 subjects with mitral regurgitation; continuous wave Doppler signals were always of low intensity with a poorly defined spectral envelope and an absence of high velocities. Peak velocities ranged from 1.1 to 4.4 m/s (mean 2.3 + 0.9) and in 19 subjects were C3.5 m/s. The mean age of subjects with mitral regurgitation was significantly higher than that of subjects without mitral regurgitation (p = 0.01). Aortic regurgitation was detected in only one subject.

This study provides further evidence that valvular re- gurgitation is frequently detected by Doppler echocardiog raphy in normal subjects. Knowledge of these findings is important to avoid the potentially serious consequences resulting from an erroneous diagnosis of heart disease.

(J Am Co11 Cardiol1989;13:1540-5)

small and the age range of the subjects has been narrow. Moreover, the reported prevalence of valvular regurgitation has varied widely (12-17).

We therefore undertook this study with the following objectives: 1) to determine the prevalence of valvular regur- gitation detected by pulsed and continuous wave Doppler echocardiography in a large series of normal subjects; 2) to describe the patterns of regurgitant flow in this population; 3) to determine whether aging affects the prevalence of valvular regurgitation; and 4) to attempt to establish guidelines that might be helpful in distinguishing between “normal” and pathologic regurgitation.

Methods Study subjects. The study group consisted of 100 healthy

adult volunteers who were free of symptoms or history of cardiac or pulmonary disease. There were 52 men and 48 women, ranging in age from 23 to 89 years (mean 45 2 16). Results of physical examination of the cardiovascular sys- tem were normal in all subjects; five individuals who had a

01989 by the American College of Cardiology 0735-1097/89/$3.50

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BERGER ET AL. 1.541 DOPPLE:R ECHOCARDIOGRAPHY IN NORMAL SUBJECTS

soft early systolic murmur at the left sternal border, charac- teristic of an innocent flow murmur, were included in the study population.

Echocardiography. M-mode and two-dimensional echo- cardiograms were performed in all subjects and were ana- lyzed for chamber enlargement, ventricular hypertrophy, segmental wall motion abnormalities and ventricular func- tion. Careful attention was paid to valve leaflet morphology. All study participants had normal M-mode and two- dimensional echocardiograms. Subjects were excluded for even minor degrees of valve thickening or mitral annular calcification.

Doppler instrumentation. Doppler studies were performed with use of a phased array echocardiographic system (Irex Meridian). The system is equipped with a dual frequency transducer that operates at a frequency of 3.5 MHz for two-dimensional echocardiography and 2 MHz for the Dopp- ler examination. Blood flow velocities were graphically dis- played by means of spectral analysis and recorded at a paper speed of 50 mm/s. An audio signal was used in conjunction with the spectral display and two-dimensional image to align the ultrasound beam with flow and to position the sample volume in the desired area. A sample volume of 4 mm was used for the pulsed Doppler examination.

Doppler examination. The examination was performed with the subjects supine or in the left lateral decubitus position. Each valve was evaluated by pulsed and continu- ous wave Doppler echocardiography. The apical four cham- ber and parasternal long-axis views were used to detect mitral regurgitation. With use of pulsed Doppler ultrasound. the sample volume was placed in the left atrium just behind the mitral valve and carefully moved back and forth to detect the presence of mitral regurgitation, which was defined as a systolic velocity signal beginning with mitral closure and occupying ~50% of the duration of systole. If evidence of mitral regurgitation was found, the sample volume was moved posteriorly into the left atrium to assess the extent of the regurgitant flow. Continuous wave Doppler ultrasound was then utilized to confirm the presence of mitral regurgi- tation and to measure the maximal velocity of the regurgitant jet. This procedure was accomplished by gradually tilting the ultrasound beam from side to side and anteroposteriorly until the highest frequency audio signals were identified and the highest maximal velocity was recorded on the spectral display.

For evaluation of tricuspid regurgitation, the apical four chamber view and the parasternal short-axis and right ven- tricular inflow views were utilized. The approach was similar to that for mitral regurgitation. Tricuspid regurgitation was defined as systolic flow starting with tricuspid valve closure and lasting >50% of systole.

For detection of aortic regurgitation, the apical five chamber and long-axis views and the parasternal long-axis view were used. The sample volume was placed in the left

ventricular outflow tract just proximal to the aortic valve. Aortic regurgitation was defined as a diastolic flow distur- bance in the left ventricular outflow tract. If aortic regurgi- tation was detected, the sample volume was carefully moved into the outflow tract to determine the extent of the regur- gitant jet. Continuous wave Doppler ultrasound was then used to verify the presence of aortic regurgitation and to measure the maximal velocity of the regurgitant jet.

For detection ofpulmonary regurgitation, the parasternal short-axis view was used. Pulmonary regurgitation was defined as a diastolic flow disturbance in the right ventricular outflow tract. Recordings were obtained with the same technique described for aortic regurgitation.

Statistical analysis. Data are expressed as mean t SD. The chi-square test was utilized to compare the prevalence of right- and left-sided regurgitation and to determine whether there was any relation between gender or age and the prevalence of valvular regurgitation. The t test was used to assess the relation between valvular regurgitation and age.

Results Detection of valvular regurgitation. Valvular regurgita-

tion was detected with equal frequency by pulsed or contin- uous wave Doppler ultrasound and was present in 73 of 100 subjects. There were 46 subjects with regurgitation of one valve. 24 with regurgitation of two valves and 3 with regurgitation of three valves. Tricuspid regurgitation was detected most commonly and was present in 50 subjects. Pulmonary, mitral and aortic regurgitation were found in 3 I and 21 subjects and 1 subject, respectively. Right-sided regurgitation was significantly more frequent than left-sided regurgitation (81 versus 22 valves, p < 0.01).

Valvular regurgitation was detected with similar fre- quency in men and women. There were 5 1 regurgitant valves in 52 men and 52 regurgitant valves in 48 women (p = NS). Tricuspid regurgitation was significantly more common in women (65%) than in men (37%) (p <: 0.01). The prevalence of mitral, aortic and pulmonary regurgitation was compara- ble in male and female subjects.

There was no relation between age and the total number of regurgitant valves per subject. However. mitral regurgi- tation was detected more frequently in older individuals and was present in 13 (33%) of 40 subjects >50 years of age compared with 8 (13%) of 60 subjects ~50 years (p = 0.04). Subjects with mitral regurgitation also had a significantly higher mean age (55 t 18 years) than did those without mitral regurgitation (43 ? 15 years) (p = 0.01). No relation was found between age and tricuspid, pulmonary or aortic regurgitation.

Mitral regurgitation (Fig. 1). Doppler velocity signals in the left atrium compatible with mitral regurgitation were recorded in 2 1 subjects. The best signals were recorded from the apex in 20 subjects and from the parasternal position in

1542 BERGER ET AL. DOPPLER ECHOCARDIOGRAPHY IN NORMAL SUBJECTS

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Figure 1. Continuous wave Doppler recording obtained from the apical window in a subject with mitral regurgitation. The Doppler velocity signal is holosystolic with a poorly defined spectral enve- lope and an absence of high velocities. The peak velocity of the regurgitant jet is 2 m/s.

Figure 2. Continuous wave Doppler recording obtained from the apical window in a subject with tricuspid regurgitation. The spectral display reveals a holosystolic velocity signal of good quality with well defined borders. The peak velocity of the regurgitation jet is 2.2 m/s.

1 subject. Regurgitant flow in the left atrium was never detected > 1 cm from the mitral leaflets and in seven subjects could be recorded only at the level of the leaflets. The Doppler signal was holosystolic in 1 I subjects and had a duration (expressed as a percentage of the duration of systole) of 66% to 89% in the remaining 10 subjects. The mean duration for all subjects with mitral regurgitation was 90 2 11%. Continuous wave Doppler recordings had a similar appearance in all subjects. Doppler signals were always of low intensity with a poorly defined spectral envelope and an absence of high velocities. The peak veloc- ities ranged from 1.1 to 4.4 m/s (mean 2.3 2 0.9) and in 19 (90%) of 21 subjects were ~3.5 m/s.

Aortic regurgitation. Aortic regurgitation was detected in one subject and was characterized by a holodiastolic veloc- ity signal recorded only at the level of the aortic leaflets. Continuous wave Doppler ultrasound revealed a poorly defined spectral envelope with a dropout of high velocities and a peak velocity of 2.2 m/s.

Tricuspid regurgitation (Fig. 2). Tricuspid regurgitant flow patterns were detected in 50 subjects. The best Doppler signals were recorded from the parasternal window in 27 subjects and from the apical window in 23. Regurgitant flow in the right atrium was never recorded farther than 1 cm from the tricuspid leaflets. In 31 subjects it was detected only at the level of the leaflets. The duration of regurgitant flow ranged from 78% to 100% of the duration of systole (mean 98 -t 5%). In 41 subjects regurgitant flow was holosystolic. In contrast to mitral regurgitation, in which a complete velocity profile could never be recorded, continuous wave Doppler ultrasound (Fig. 2) revealed a complete spectral envelope with well defined borders in 32 subjects (64%) with tricuspid regurgitation. The peak velocity recorded by con-

tinuous wave Doppler ultrasound ranged from 0.8 to 2.3 m/s (mean 1.8 ? 0.4). For the 32 subjects in whom a complete velocity profile was recorded, the peak velocity ranged from 1.7 to 2.3 m/s (mean 2.0 ? 0.2).

Pulmonary regurgitation (Fig. 3). Pulmonary regurgita- tion was present in 31 subjects; the pulmonary valve was clearly visualized during diastole in 24 of these 3 1. In none of the 24 was regurgitant flow detected farther than 1 cm from the valve and in 18 subjects it was present only at the level of the leaflets. Doppler signals covered from 63% to 95% (mean 81 ? 8%) of diastole. Regurgitant flow was not recorded in early diastole in any subject. The interval from pulmonary closure to the onset of regurgitant flow varied from 20 to 120 ms (mean 70 t- 27). In 10 of the 31 subjects, there was a fall in velocity during late diastole. This decrease was attributed to an increase in right ventricular end- diastolic pressure resulting from right atria1 contraction. Peak velocity recorded by continuous wave Doppler ultra- sound (Fig. 3, left) ranged from 1.2 to 1.9 m/s (mean 1.5 2 0.2).

Discussion Detection of valvular regurgitation in normal subjects.

The reported prevalence of valvular regurgitation detected by Doppler echocardiography in normal individuals has shown marked variability (12-17). In the present study of 100 normal subjects, 50 had tricuspid regurgitation, 31 had pulmonary regurgitation, 21 had mitral regurgitation and 1 had aortic regurgitation. We found pulsed and continuous wave ultrasound techniques to be equally sensitive in detect- ing the presence of regurgitant flow. Although Doppler color flow mapping was not employed, use of this technique might have increased the observed prevalence even further (18).

JACC Vol. 13, No. 7 BERGER ET AL. 1543 June 1989: 1540-j DOPPLER ECHOCARDIOGRAPHY IN NORMAL SUBJECTS

Figure 3. Doppler recordings obtained from the parastemal window in two subjects with pulmonary regurgitation. Left panel, Continuous wave record- ing. Note the absence of flow signals in early diastole and the delayed onset of regurgitant flow (small arrows); the peak velocity is 1.4 m/s. Right panel, Example of a pulsed Doppler recording from another subject. Again, no flow is recorded in early diastole. Note the decrease in velocity (large arrows) in late diastole, which is due to an in- . . . . . . . . . crease in right ventncular end-dlastolK pressure resulting from right atria1 con- traction. The peak velocity is 1.5 m/s. PC = pulmonary closure.

Prevalence of left-sided regurgitation. One reason for differences in the reported prevalence of Doppler-detected mitral regurgitation has been the lack of uniform diagnostic criteria. In a recent study, Kostucki et al. (14) found evi- dence of mitral regurgitation in 40% of their study popula- tion. However, they included subjects with regurgitant flow limited to early systole. Dang et al. (19) found that patients with an early systolic flow pattern did not have angiographic evidence of mitral regurgitation. Abbasi (20) noted early systolic flow in normal subjects especially when the sample volume was positioned close to the mitral valve. It has been suggested that movement of blood caused by closure of the mitral leaflets might be responsible for this finding. In our study, mitral regurgitation was present in 21% of the study group and flow was holosystolic or almost holosystolic in all subjects. Comparable findings were noted by Yock et al. (13), who found mitral regurgitation in 10% of normal subjects. In the study reported by Kostucki et al. (14), regurgitant flow persisting for >50% of systole was present in 16% of subjects. Thus, when similar diagnostic criteria are used, differences in the reported prevalence of mitral regur- gitation are small.

Aortic regurgitation has rarely been noted in normal individuals. In our study we detected it in only one subject. Similar findings have been reported by other investigators (2,13,17).

Prevalence of right-sided valvular regurgitation. Most studies have shown a preponderance of right-sided regurgi- tant flow in normal subjects; the prevalence has ranged from 11% to 95% for tricuspid regurgitation (13,14,17) and 18% to 92% for pulmonary regurgitation (12-14,16,17). There are several reasons for these discrepancies. Pollak et al. (21), utilizing color Doppler flow mapping as well as conventional pulsed Doppler ultrasound, found that trained female run- ners had a much higher prevalence of right-sided regurgita- tion than did sedentary control subjects. The frequency of right-sided regurgitation appeared to correlate with the de- gree of physical conditioning. Others (22) have suggested

that some cases of pulmonary regurgitation may actually represent coronary blood flow. However, Fusejima (23) analyzed coronary blood flow with pulsed Doppler echocar- diography and found an average peak velocity in the left anterior descending coronary artery of 0.34 m/s. This value is significantly lower than the usual peak velocity of pulmo- nary regurgitant flow. Thus, differentiation from coronary blood flow should be possible on the basis of peak velocity measurements. Body habitus may also affect the ability to detect right-sided regurgitation. In individuals with a narrow anteroposterior chest diameter, the transducer can be posi- tioned closer to the right side of the heart, thereby increasing the likelihood that regurgitant flow will be detected.

Thus, it is likely that no single factor is responsible for the marked variability in the reported prevalence of right-sided regurgitation in normal subjects. Rather, it appears related to certain differences in the characteristics of the study group. In addition, differences in sensitivity of Doppler equipment and the technical skills of the echocardiographer may be contributory factors.

Characteristics of mitral regurgitant flow. Mitral regurgi- tation characteristically produced a holosystolic or almost holosystolic velocity signal of weak intensity with a poorly defined spectral envelope and a poor representation of the highest velocities. As noted by Hatle and Angelsen (24), the intensity of the Doppler signal is related to the severity of the regurgitation and, when the Doppler signal is weak, the highest velocities may be difficult to record. Similar Doppler recordings may also be obtained when the ultrasound beam is not adequately aligned with the regurgitant jet. However, this result was unlikely in our study because multiple trans- ducer positions were utilized in an attempt to record the best velocity signals. In addition, this pattern was consistently seen in all subjects with mitral regurgitation, suggesting that it was related not to inadequate alignment of the ultrasound beam but to a weak regurgitant Doppler signal.

The peak velocity of the regurgitant jet in mitral regurgi- tation is related to the pressure difference between the left

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ventricle and the left atrium during systole. Normal systolic pressure in the left ventricle generally is >lOO mm Hg, whereas left atria1 pressure is ~12 mm Hg. Based on the modified Bernoulli equation, this pressure difference should result in a peak regurgitant velocity >4 m/s. Despite this expectation, peak velocities were <4 m/s in most subjects. One explanation is that the highest velocities were not recorded because of a weak Doppler signal. It is also possible that the modified Bernoulli equation may not apply to the small regurgitant orifices present in normal subjects. As shown by Holen et al. (25), when the orifice diameter is < 1.5 mm, viscous friction may result in a peak velocity that is lower than expected. Regardless of the mechanism, peak velocities were ~3.5 m/s in 19 of 21 subjects with mitral regurgitation. Therefore, if continuous wave Doppler echo- cardiography reveals a well defined spectral envelope with a peak velocity >4 m/s or if regurgitant flow can be recorded farther than 1 cm from the valve by pulsed Doppler ultra- sound, the findings may indicate abnormal regurgitation and should be carefully correlated with the clinical status of the patient.

Characteristics of tricuspid regurgitant flow. The contin- uous wave Doppler recordings in tricuspid regurgitation were characterized by a well defined spectral envelope. It has been suggested (21) that the relative ease with which tricuspid regurgitation can be recorded in normal individuals is related to the proximity of the Doppler transducer to the right side of the heart, especially when the parasternal window is utilized. Our findings do not support this concept. We detected tricuspid regurgitation with almost equal fre- quency from the apical and parasternal windows. Other investigators (26,27) have described similar findings.

There is no dejnitive method for distinguishing normal from pathologic tricuspid regurgitation. Nevertheless, pulsed Doppler detection of regurgitant flow farther than 1 cm from the tricuspid valve or elevated peak velocities suggesting right ventricular systolic hypertension may be indicative of an abnormality (28). It should also be recog- nized that pathologic tricuspid regurgitation may be detected with normal peak velocities when pulmonary artery pressure is normal.

Characteristics of pulmonary regurgitant flow. A distinc- tive finding in subjects with pulmonary regurgitation was the absence of regurgitant flow in early diastole; others (14,29) have also noted this flow pattern in normal individuals. Interestingly, the diastolic murmur of pulmonary regurgita- tion in patients with normal pulmonary artery pressures may also have a delayed onset (30-32). This possibility has been attributed to the lack of a significant pressure gradient between the pulmonary artery and the right ventricle during early diastole (33). It is unclear whether a comparable mechanism is also responsible for the absence of early diastolic flow observed in the present study.

Age and valvular regurgitation. Aging has been reported to affect the prevalence of valvular regurgitation. Akasaka et al. (15) studied healthy volunteers >40 years of age with pulsed Doppler echocardiography and found that valvular regurgitation increased progressively with age, especially with regard to aortic regurgitation. Our findings differed in that aortic regurgitation was detected in only one subject. In addition, we found no relation between right-sided regurgi- tation and age. We did find that the mean age of those subjects with mitral regurgitation was significantly higher than that of subjects in whom mitral regurgitation was not detected. These discrepancies may in part be related to differences in the mean age of our study population (45 years) compared with that of Akasaka et al. (69 years) (15).

Clinical implications. This study provides additional evi- dence that mild valvular regurgitation is frequently detected by Doppler echocardiography in normal individuals. Al- though the precise cause of these flow patterns has not been identified, recent reports (12,13,15,18,34) suggest that they represent true valvular regurgitation.

This study also helps define the characteristics of valvular regurgitant flow patterns that may be recorded in normal subjects. In our study population, tricuspid and pulmonary regurgitation typically did not extend farther than 1 cm from the valve, and peak velocities were within normal range. Mitral regurgitation was characterized by a low intensity Doppler signal with a poorly defined spectral envelope and was never detected farther than 1 cm from the valve. Aortic regurgitation was rarely found in our normal subjects.

Therefore, Doppler-detected mitral, tricuspid and pulmo- nary regurgitation with these characteristics can be a nor- mal or physiologicjnding. Aortic regurgitation, on the other hand, is rarely found in normal individuals and its presence should always raise the suspicion of valvular heart disease. Awareness of these findings is essential to avoid the poten- tial consequences resulting from an erroneous diagnosis of heart disease. It is important that no clinical decision be based solely on the detection of regurgitant flow by Doppler examination. Rather, the Doppler findings should be corre- lated with other clinical factors before arriving at a conclu- sion.

We thank Rubie Senie, PhD for assistance with the statistical analysis and Helen Wegsman for preparation of the manuscript.

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