The relationship between systolic notch duration of right ventricular outflow tract Doppler flow spectrum and gestational age and pulmonary blood flow

Introduction

Right ventricular outflow tract (RVOT) systolic notch of Doppler flow pattern (spike and dome morphology) can be seen in adult patients with pulmonary hypertension or/pulmonary embolism (1,2); however, it is common in normal fetuses (3). Up to now, the relationship between RVOT systolic notch parameter and gestational age (GA) has remained unknown.

Fetal pulmonary vessels are in the process of continuous development and not yet mature, and fetal pulmonary resistance and pulmonary artery pressure are also constantly changing throughout pregnancy (4-6). Clarifying the relationship between RVOT systolic notch parameter and pulmonary hemodynamics in fetuses may help to improve the evaluation of lung development.

In the present study, we evaluated the changes in RVOT pulsed-wave Doppler envelope characteristics (including systolic notch) with GA, and their correlation with pulmonary hemodynamics, in order to find a new, simple, and useful ultrasonic biological indicator for the assessment of fetal pulmonary vascular bed development. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-450/rc).

Methods

Study population

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Human Research Ethics Committee of Yangpu Hospital, School of Medicine, Tongji University (No. LL-2024-ZRKX-025). Written informed consent was provided by all participants prior to enrollment. Between January 2024 and December 2024, 131 fetuses of singleton pregnancy were prospectively enrolled in antenatal care centers. GA was calculated from the first date of the last menstrual period and confirmed by sonography. These fetuses were evaluated by clinical and physical assessments, chromosome examinations, and sonographic examinations. The pregnant women (mean age, 30.7±5.2 years; range, 21–42 years) were evaluated by clinical and physical assessments, laboratory data, electrocardiography, and sonographic examination. The inclusion criterion for the fetuses and pregnant women was the absence of any focal or diffuse disease at any of the examined organs. Pregnant women with risk factors, such as diabetes mellitus, hypertension, congenital heart diseases, pulmonary diseases, cardiomyopathy, and endocrine diseases, and fetuses with poor two-dimensional (2D) echo imaging quality, were excluded from the study.

Echocardiographic measurements

A complete fetal echocardiogram was performed by an experienced ultrasound expert (with 20 years of clinical experience in fetal echocardiography), using a commercially available ultrasound system (EPIQ 7C; Philips, Andover, MA, USA) equipped with a C5-1 transducer. Poor image quality was defined as the inability to clearly visualize endocardial borders for accurate Doppler sampling by two experienced sonographers. During the screening for structural heart diseases, each fetus underwent a series of measurements of right ventricular (RV) function and pulmonary hemodynamics. Right ventricular fractional area changes (RVFACs), main pulmonary artery diameters (PADs), and ductus arteriosus diameters (DADs) were obtained by real time 2D echo method. Tricuspid annular plane systolic excursions (TAPSEs) were obtained by M-mode echo method. Heart rate (HR), pulmonary artery flow acceleration times (PAATs), velocities (PAVs), and velocity-time integrals (PAVTIs), as well as ductus arteriosus velocities (DAVs) and VTIs (DAVTIs) were obtained by Doppler echo method. R-R interval was calculated according to the following formulas: R-R interval (milliseconds, ms) = 60/HR ×1,000. All the values were measured from 5 consecutive beats and averaged. Right ventricular cardiac output (RVCO) (milliliters per minute, mL/min) and ductus arteriosus shunt (DAS, mL/min) were calculated respectively according to the following formulas: blood flow per minute (mL/min) = π × D²/4 × VTI × HR (7-10), where π is the ratio of the circumference of a circle to its diameter, D is the abbreviation for diameter, referring to PADs and DADs, respectively, and VTI is the abbreviation of the velocity-time integral, referring to PAVTI and DAVTI, respectively. Pulmonary blood flow (PBF, mL/min) was obtained using the following formula: PBF = RVCO − DAS (8,9).

For acquiring RVOT pulsed-wave Doppler flow spectra, the parasternal short-axis view at the level of the aortic valve was found by adjusting the position of the pregnant women or/and the position of the transducer, so that RVOT could be clearly displayed. The gain was adjusted in order to obtain a high contrast to eliminate the presence of artifacts. A pulsed-wave Doppler sample volume of 1–2 mm was placed at the RVOT distal end just below the pulmonary valves (about 1–2 mm), with a fast scanning speed (132 mm/s). The scale was set at 40–80 cm/s to keep low-speed blood flow signal from being missed, and adjusted if necessary. The pulsed-wave Doppler flow spectrum of RVOT showed a typical ‘spike and dome’ morphology, and the ‘systolic notch’ pattern was visible (Figure 1). All the pregnant women were encouraged to hold their breath at the end of expiration in order to reduce the artifacts of their abdominal wall movements as far as possible. The Doppler spectra of at least five cardiac cycles were stored digitally for subsequent analysis. Quantitative measurements were performed on the Doppler spectra as follows (Figure 1): the peak spike and dome velocities measured at the peak of respective wave forms in centimeters per second (cm/s) were defined as spike and dome velocities, and the lowest velocities measured in cm/s at the bottom between spike and dome (nadir of notch) were defined as notch velocities. The duration times of the total flow pulsed Doppler spectrum of RVOT (total durations), the duration times of spike (spike durations) and dome (dome durations) were measured in ms from the beginning to the end of each corresponding wave forms, respectively. The times between the moments of peak spike velocities and peak dome velocities were defined as notch durations. The acceleration times of spike were measured in ms as the times from the beginning of RV ejection to the moments of the peak velocities of spike, and the acceleration times of dome were measured in ms as the time from the moments of notch nadir velocity to the moments of the peak velocity of dome. The deceleration times of spike were measured in ms as the times from the moments of the peak velocities of spike to the moments of notch nadir velocities, and the deceleration times of dome were measured in ms as the times from the moments of the peak velocities of dome to the moments of the end of RV ejection. Acceleration and deceleration slopes of spike and dome were calculated by the built-in software package using the same time points described for respective time measurements mentioned above. The VTIs of the total RVOT flow pulsed Doppler spectra (total VTIs) and the VTIs of spike and dome were calculated by the built-in software package after manually tracing their respective Doppler envelope. All the values were measured from 5 consecutive beats and averaged. Finally, the ratios of spike duration to R-R interval, notch duration to R-R interval, dome duration to R-R interval, total duration to R-R interval, spike to dome duration, spike to total duration, dome to total duration, notch to spike duration, notch to dome duration and notch to total duration, the ratios of spike to dome velocity, notch to spike velocity, notch to dome velocity, the ratios of spike to dome VTI, spike to total VTI, and dome to total VTI, were calculated sequentially.

Figure 1 Right ventricular outflow tract Doppler tracing in a normal fetus at 26 weeks of gestation, illustrating the characteristic systolic notch pattern and the measurement methodology of all waveforms.

Statistical analysis

All continuous data were confirmed to be normally distributed by the Shapiro-Wilk test (P>0.05 for all variables) and are presented as mean ± standard deviation. Comparisons between groups were performed using the independent samples t-test. Pearson correlation analysis was performed to compare the relationship between RVOT systolic notch parameters of Doppler flow pattern and GA and PBF. Nonlinear regression analysis used to deduce the regression equation for the optimal parameter of RVOT systolic notch and GA regression equation. A receiver operating characteristic (ROC) curve analysis of RVOT systolic notch parameters was used to differentiate between second- and third-trimester and determine the optimal cut-off points and validity parameters. A value of P<0.05 was considered statistically significant. Statistical analyses were processed using the statistical software SPSS 19.0 (IBM Corp., Armonk, NY, USA) and MedCalc 16.8.4 (MedCalc Software, Ostend, Belgium; http://www.medcalc.org).

Results

Baseline characteristics

Of the 131 fetuses, 6 were excluded due to poor 2D echo imaging quality, 1 was excluded due to congenital heart disease, and 124 fetuses [second-trimester group: n=64; GA: 176.34±13.27 days; estimated fetal weight (EFW): 792.39±123.87 g; third-trimester group: n=60; GA: 242.62±22.43 days; EFW: 2,257.19±451.52 g] were eventually included in the study. As shown in Table 1, there was no significant change in HR and RVFAC from the second trimester to the third trimester (P>0.05). The third-trimester group had greater TAPSE, PA AT, more RV output, and higher PBF than the second-trimester group (P<0.05). Although the DAS increased with GA, the ratios of PBF to RVCO were still increased.

RVOT pulsed-wave Doppler envelope characteristics

The RVOT systolic notch of Doppler flow pattern was observed in all the fetuses. As shown in Table 2, notch duration, notch duration to R-R interval ratio, and notch velocity were significantly greater in the third-trimester group than they were in the second-trimester group (P<0.01), whereas spike duration, dome duration, total duration, spike velocity, and dome velocity did not differ between the second- and third-trimester groups (P>0.05), and therefore notch to spike duration ratio, notch to dome duration ratio and notch to total duration ratio, as well as notch to spike velocity ratio and notch to dome velocity ratio increased significantly from the second to third trimesters (P<0.05). Spike deceleration time and dome acceleration time were all significantly greater in the third-trimester group than in the second-trimester group (P<0.05), whereas there was no difference in spike deceleration and dome acceleration between the second- and third-trimester groups (P>0.05). In addition, spike VTI, dome VTI, total VTI, and the VTI ratio of spike to dome were increased from the second trimester to the third trimester (P<0.05).

Relationship between RVOT Doppler flow parameters and GA

As shown in Table 3, multiple time, velocity, and VTI parameters were positively correlated with GA. The same was true of spike acceleration, spike deceleration time, dome acceleration time and dome deceleration. Only spike to dome VTI ratio had a negative correlation with GA. Among all the parameters which correlated with GA, the correlation coefficient of notch duration (r=0.726, P<0.0001), notch duration to R-R interval ratio (r=0.644, P<0.0001), and notch to dome duration ratio (r=0.628, P<0.0001) ranked in the top three. The nonlinear regression equation for notch duration and GA was:

y=220.5918−1.3552x+0.004322x2(R2=0.527;P<0.001)[1]

where x and y represent GA (days) and notch duration, respectively.

Relationship between RVOT Doppler flow parameters and PBF

As shown in Table 4, multiple RVOT Doppler flow parameters exhibited significant correlations with PBF. Among them, notch to spike duration ratio (r=0.652, P<0.0001), notch duration (r=0.624, P<0.0001), and notch duration to R-R interval ratio (r=0.586, P<0.0001) showed the strongest correlations with PBF.

Performance of RVOT Doppler flow parameters on differentiating between second- and third trimesters

ROC analysis was performed to evaluate the ability of notch duration, notch duration to R-R interval ratio, notch to dome duration ratio, and notch to spike duration ratio to differentiate between the second and third trimesters. As shown in Figure 2, the area under the ROC curve (AUC) was highest for notch duration [0.872; 95% confidence interval (CI): 0.798–0.927], followed by the notch duration to R-R interval ratio (0.824; 95% CI: 0.723–0.900). Both were higher than the AUC values for the notch to dome duration ratio (0.808; 95% CI: 0.701–0.889) and the notch to spike duration ratio (0.694; 95% CI: 0.579–0.794). The optimal cutoff value for notch duration was 132 ms, yielding a sensitivity of 82.50%, a specificity of 91.46%, and an accuracy of 88.52%.

Figure 2 Receiver operating characteristic curve showing the performance of right ventricular outflow tract Doppler flow parameters on differentiating between second and third trimesters. AUC, area under the curve.

Discussion

To our knowledge, this study is the first to systematically report and measure the parameter ‘notch duration’ in the fetal RVOT Doppler spectrum. In this study, we explored the relationships of notch duration and other Doppler flow parameters of RVOT with GA, and tried to elucidate the possible hemodynamic mechanism underlying them. We believe this study has important value in evaluating fetal pulmonary vascular bed development.

Midsystolic semiclosure and other abnormal echo patterns of the pulmonary valve have been reported to be useful in assessing pulmonary hypertension in adult humans (2), and the hemodynamic determinants of pulmonary valve motion during systole has been clarified in a dog model of experimental pulmonary hypertension (11). Systolic notch pattern (‘spike and dome’ morphology) of RVOT pulsed Doppler flow spectra can be explained by the changes in pulmonary artery-right ventricular (PA-RV) pressure gradient during the cardiac cycle. Normally, the PA pressure is less than the RV pressure, and PA-RV pressure gradient is always negative in systole. When in a pulmonary hypertension state, the PA-RV pressure gradient is negative in early systole, with rapid opening of the pulmonary valves and a sharp rise of flow. In midsystole, due to rapid filling of the pulmonary vascular bed and lower compliance, pulmonary arterial pressure increases sharply, PA-RV pressure gradient becomes positive, and pulmonary valves close partially, with a sharp decline of flow. So far, the ascending branch and descending branch of spike (i.e., notch left slope) and notch foot are formed. Next, with pulmonary blood flowing slowly into the left atrium, the PA-RV pressure gradient gradually becomes negative again, the orifice of the pulmonary valves gradually enlarge from semiclosure to full opening, and blood flow speeds up again until it reaches its peak velocity. At this time, a complete systolic notch (left slope, notch nadir, and right slope) is formed. In end-systole, due to a gradually decreased RV contractility, the PA pressure is greater than the RV pressure, and the PA-RV pressure gradient is positive again, with a slow closure and then rapid closure of the pulmonary valves and a slow decrease followed by a rapid decrease of flow. At this time, the ascending branch (i.e., right slope of notch) and descending branch of dome are formed. From the process mentioned above, we know that the systolic notch is caused by the midsystolic semiclosure of the pulmonary valves in a pulmonary hypertension state. It is well known that fetal pulmonary blood vessels continue to differentiate. They are in a state of contraction, and the pulmonary arterial pressure is relatively high. The formation mechanism of fetal systolic notch (i.e., ‘spike and dome’ morphology) can be explained with the help of determinants of RVOT Doppler flow spectral characteristics in adults with pulmonary hypertension.

In our study, PBF was significantly increased (>2 times) in the third trimester compared to the second trimester, which is one of the main hemodynamic parameters that change during fetal lung development. This finding had been confirmed by the study of Hislop et al. on fetal lung anatomy in humans (12) and the study of Levin et al. on fetal lung anatomy in lambs (13).

An increase in the total number of vessels, an increase in PADs and increased vasomotor reactivity, we think, can account for increased PBF with GA. Under the condition of pulmonary hypertension, increased PBF (stretched pulmonary vascular bed) during fetal life resulted in a prolonged positive PA-RV pressure gradient and a continuous midsystolic semiclosure of the pulmonary valves, and therefore resulted in a prolonged notch duration. In addition, the prolonged spike deceleration time and dome acceleration time, and the increase of notch velocities from second trimester to third trimester, also indicated the increase of PBF.

Our results can also be supported by another study on pulmonary embolism (1). The RVOT systolic notch of Doppler flow pattern was located within the initial 50% of ejection (early systolic notch) in patients with submassive pulmonary embolism extending into main pulmonary artery or branch pulmonary arteries, but it located within the second half of the systolic ejection period (midsystolic notch) in patients with subsegmental pulmonary embolism and thrombi in branches of the right and left main pulmonary arteries. The times between the moments of peak spike and dome velocities, namely, notch durations, in the latter were longer than the former. These findings indicate that the length of notch duration is related to the effective pulmonary vascular bed capacity. For the fetus, it is related to the development of fetal pulmonary vascular bed.

In our study, we found there were no differences between second- and third-trimester according to HR, spike duration, dome duration, and total duration. However, the shape of systolic notch (‘spike and dome’ morphology) was in dynamic change, that is, the time when the peak velocity of spike and dome appeared, and their slope of rising and falling were constantly changing. The corresponding parameters were mainly notch duration, notch velocities, spike deceleration time/deceleration, and dome acceleration time/acceleration. These findings were consistent with the physiological changes in fetal pulmonary hemodynamics mentioned above. Through statistical analysis, we concluded that the correlation coefficient of notch duration, notch duration to R-R interval ratio, and notch to dome duration ratio ranked in the top three among the Doppler flow parameters of RVOT which correlated with GA. They all correlated well with PBF. Reasonably, notch duration had the highest performance among these parameters on differentiating between second- and third-trimesters.

Limitations

Our study was inevitably affected by several factors. First, the sample size was small and the single-center design may limit generalizability. It is hard to avoid the deviation of statistical results. Studies based on larger populations would be more persuasive. Second, due to the limited position of fetuses in the third-trimester group, Doppler angle was affected, which might result in deviations in the measurement values of blood flow velocity and VTI. In addition, longitudinal studies are needed to verify the prognostic value of RVOT hemodynamic parameters and confounding factors that may affect fetal hemodynamics, such as maternal conditions, still require further study.

Conclusions

The measurement of RVOT systolic notch parameters of Doppler flow patterns is simple and convenient. Despite certain limitations, notch duration—one of these parameters—shows a statistically significant correlation with both GA and PBF. Thus, it appears to be a promising ultrasonic biological indicator for evaluating the development of the fetal pulmonary vascular bed.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-450/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-450/dss

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-450/coif).The authors have no conflicts of interest to disclose.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Human Research Ethics Committee of Yangpu Hospital, School of Medicine, Tongji University (No. LL-2024-ZRKX-025). Written informed consent was provided by all participants prior to enrollment.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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