Fetal cardiac function: Feasibility in obtaining the right modified myocardial performance index in a single Doppler waveform

Abstract

Objective

We aimed to assess the feasibility of assessing the fetal right Myocardial Performance Index (RMPI) using single waveform and to compare absolute values with dual technique.

Methods

We studied 145 morphologically normal appropriately grown fetuses at 16–28 weeks’ gestation with local Ethics Committee approval using fixed machine settings: Doppler sweep velocity at 15 cm/s; angle of insonation <15⁰; wall motion filter 300 Hz. Doppler gate was 3 mm, increased to 4–5 mm if needed. RMPI was obtained twice in the same fetus; using ‘dual‐image’ and ‘single‐image’ techniques. Dual images were acquired as previously described. Single images were taken from the tip or just below the tricuspid valve towards the ventricular septum in the apical four‐chamber view. RMPI was calculated using two‐value (a–b/b) or three‐value (ICT+IRT/ET) formulae where ‘a’, ‘b’ or (ET) represent the isovolumetric and ejection times, and ICT and IRT represent the isovolumetric contraction and relaxation times.

Results

Dual image was accessible in 100% of fetuses. Single‐image acquisition was 100%, 92.3% and 76.5% at 16⁺⁰–24⁺⁰, 24⁺¹–27⁺⁰, and 27⁺¹–28⁺⁰ weeks respectively (95.2% overall). Doppler gate increased in 23 cases (16.6%); 8/17 (47%) at 27⁺¹–28⁺⁰ weeks’ gestation. Mean and standard deviation for ‘dual image’ and ‘single image’ were: RMPI 0.46 ± 0.09 and 0.49 ± 0.07; ‘a’ 249.06 ± 11.50 and 249.11 ± 11.93; ‘b’ 170.85 ± 8.95 and 167.62 ± 8.39.

Conclusions

Single‐image acquisition RMPI is highly feasible from 16 to 26 weeks gestation. Difference in mean values may represent overestimation of ejection time in the ‘dual‐image’ technique.

Introduction

The Myocardial Performance Index (MPI) was initially proposed for adult cardiology as a non‐invasive Doppler derived index of global cardiac function,1, 2 subsequently extrapolated to fetal cardiology using the same methodology as described by Tei et al. and then later modified by Hernandez‐Andrade et al. (Mod‐MPI).3 For the left MPI (LMPI), both inflow and outflow can be recorded in one Doppler waveform by placing the Doppler sample volume in the left ventricle at the junction of the anterior leaflet of the mitral valve and the left ventricular outflow tract in the apical five chamber view of the heart.4 Anterior displacement of the pulmonary valve (PV) means that measurement of the right MPI has been assumed to require two separate Doppler waveforms for measurement; tricuspid inflow and pulmonary outflow waveforms.3

The time period ‘a’ is measured from the end of the A‐wave to the beginning of the next E‐wave during the ventricular filling phase of the tricuspid waveform. The ejection time ‘b’ is the duration of ventricular outflow from the pulmonary waveform. The sum of ICT and IRT can be calculated by subtracting this ejection time from the interval between cessation and onset of tricuspid inflow, that is, ‘a’ time period. For the right ventricle, the isovolumetric times (ICT and IRT) cannot be measured individually, the RMPI being calculated as (a–b)/b.

Following the introduction of Mod‐MPI, it has been applied to a number of pathologies in the second and third trimester including diabetes,5, 6, 7, 8 twin‐twin transfusion syndrome,9, 10, 11, 12 fetal cardiac abnormalities,13, 14 pre‐eclampsia,15, 16 intrauterine growth retardation17, 18, 19 and other fetal conditions,20, 21, 22 although most work has focused on the LMPI.

Given the potential for inaccuracies introduced to the RMPI by the need for 2 unrelated waveforms, we aimed in this study to assess feasibility of acquisition, repeatability and absolute values of the RMPI with both single and dual Doppler waveforms at 16–28 completed weeks of gestation.

Methods

A prospective cross sectional study of 148 normal fetuses at 16–28 completed weeks of gestation was performed with local ethics committee approval (SESIAHS HREC Ref 8/168). Examinations were performed using a Voluson 8 Expert ultrasound machine (GE Medical Systems, Sydney, Australia), using linear or curved array transducers (3.5–7 MHz). Images were stored to the ultrasound hard drive for calculation of time intervals using the inbuilt fetal cardiology settings on the machine. Mechanical index (MI) and thermal index (TI) were kept below 1. Informed consent was obtained at the time of recruitment. The gestational age was calculated based on the last menstrual period and confirmed by measurements taken at dating or first trimester scan. Mothers with medical conditions and/or taking medication were not excluded from the study providing no structural fetal abnormality was detected in the morphology scan and the fetus had normal growth for gestation. Mothers underwent a single ultrasound scan for this study and the images were taken in triplicate at each scan for each studied parameter. Doppler waveforms were obtained in the absence of fetal body movements and with the mother in voluntary suspended respiration.

The RMPI images were taken by single examiner using two techniques based on variation in placement of the Doppler gate that used the tricuspid and pulmonary valve clicks as reference points to calculate time intervals. The ‘dual image’ was taken as previously described23 using two separate waveforms from two different anatomical planes, as shown in Figures 1 and 2.24 The Doppler gate was initially placed at the tips of the tricuspid valve leaflets in the apical four‐chamber view (tricuspid inflow). It was then placed at the pulmonary valve in the short‐axis view or in a sagittal plane, where the main pulmonary artery and its continuation into the descending aorta is seen (right ventricular outflow). The ‘single image’ was obtained by placement of Doppler gate at the tips or just below TV medially towards the ventricular septum in the apical four‐chamber view including both tricuspid inflow and pulmonary outflow as shown in Figure 3. This created a Doppler waveform similar to the LMPI. For visual consistency, the tricuspid inflow was kept below and the pulmonary outflow above the Doppler base line.

Figure 1.

Right modified Myocardial Performance Index (RMPI) anatomical planes: a) The tricuspid inflow, with the Doppler gate at the tips of the tricuspid valve leaflets in the apical four‐chamber view; b) The pulmonary outflow, with the Doppler gate at the level of the pulmonary valve in the short‐axis view; c) The pulmonary outflow in a sagittal plane, with the Doppler gate at the level of the pulmonary valve.

Figure 2.

The two constituent waveforms of the two‐waveform right modified Myocardial Performance Index (RMPI): a) The tricuspid inflow waveform and ‘a’ interval; b) The pulmonary outflow wave form and ‘b’ interval.

Figure 3.

a) ‘Single‐image’ right modified Myocardial Performance Index (RMPI) anatomical plane: placing the Doppler gate at the tips or just below TV medially towards the ventricular septum in the apical four‐chamber view aiming for including tricuspid inflow and pulmonary outflow in a single Doppler waveform. b) Doppler trace of ‘single‐image’ RMPI.

Fixed machine settings were set for all waveforms: Doppler sweep velocity at 15 cm/s; angle of insonation <15⁰; minimal gain; wall motion filter 300 Hz. Doppler gate was set at 3 mm and increased to 4–5 mm if needed. Three cardiac cycles were evaluated for each fetus in each technique.

Time interval ‘a’ was measured from the tricuspid valve closure to the tricuspid valve opening and ‘b’ was measured from the pulmonary valve opening to the pulmonary valve closure. All time intervals were measured in milliseconds at the peak of the corresponding valve clicks. The RMPI was calculated using two‐value formula as (a–b)/b for both techniques to allow a fair comparison. In addition, the RMPI in the ‘single image’ was calculated once again using the three‐value formula (ICT+IRT/ET) in order to evaluate the effect of two‐value measurement error on calculated RMPI.

Statistical analysis was performed using SPSS version 22 (SPSS Inc., Chicago, IL, USA). RMPI values were expressed as mean ± standard deviation. Data were analysed using two‐way mixed model correlation coefficients (ICCs) and 95% confidence intervals (95% CI) for absolute agreement. Comparison between the two techniques was performed by Bland‐Altman method of agreement. The right ventricular heart rate (HR) in the ‘dual method’ was calculated as the mean of (‘a'HR) and (‘b'HR) heart rates. Paired t‐test was used for comparison of heart rate in ‘dual‐image’ and ‘single‐image’ techniques.

Results

148 mothers were recruited for this study. Three cases were excluded; two cases for fetal anomalies and one case for fetal tachycardia. All studied fetuses were appropriately grown, with fetal weight calculated using Hadlock formula using head circumference, biparietal diameter, abdominal circumference and femur length measurements. They had normal morphologic findings and were in normal sinus rhythm. ‘Single‐image’ acquisition rate was 100% (n = 89); 92.3% (n = 39); 76.5 (n = 17) at 16⁺⁰–24⁺⁰, 24⁺¹–27⁺⁰, and 27⁺¹–28⁺⁰ weeks respectively as shown in Figure 4. The RMPI was accessible in all fetuses using ‘dual image’, whereas it could be obtained in 138 cases (95.2%) in ‘single‐image’ technique. The Doppler gate was maintained at 3 mm in all cases of ‘dual image’. However, it needed to be increased to 4–5 mm (in order to obtain a clear Doppler waveform) in 23 cases (16.6%) of ‘single‐image’ technique predominantly at 27⁺¹–28⁺⁰ weeks’ gestation (8/17; 47%).

Figure 4.

The acquisition rate of right Myocardial Performance Index (RMPI) using ‘single‐image’ technique from 16 to 28 weeks’ gestation.

Comparison between ‘dual‐image’ and ‘single‐image’ techniques was performed for 138 fetuses where both were successfully obtained. For ‘dual‐image’ and ‘single‐image’ techniques, mean and standard deviation for RMPI using (a–b)/b was 0.46 ± 0.09 and 0.49 ± 0.07; for ‘a’ was 249.06 ± 11.50 and 249.11 ± 11.93; for ‘b’ was 170.85 ± 8.95 and 167.62 ± 8.39. Intra‐observer repeatability of RMP showed ICC (95% CI) of 0.94 (0.93–0.96) and 0.91 (0.88–0.93) for ‘dual image’ and ‘single image’ respectively. The repeatability of constituent time intervals for both ‘dual image’ and ‘single image’ were comparable and showed good repeatability as shown in Table 1. The mean ± SD of ‘single image’ using three‐value formula was 0.49 ± 0.07.

Table 1.

Intra‐class correlation coefficients (ICCs) and 95% confidence intervals (95% CI) for the right Myocardial Performance Index (RMPI) and its constituent time intervals

RMPI	Factor	ICC	95% CI
‘Double‐image’	‘a’	0.948	0.932–0.961
	‘b’	0.962	0.952–0.973
	MPI	0.943	0.925–0.957
‘Single‐image’	‘a’	0.929	0.907–0.946
	‘b’	0.953	0.938–0.965
	MPI	0.905	0.876–0.928

Agreement between ‘dual image’ and ‘single image’ in the same fetus showed a mean difference of 0.03 (95% LA, −0.13 to 0.18), 0.05 (95% LA, −15.48 to 15.58), and −3.23 (95% LA, −21.85 to 15.40) for RMPI, ‘a’ and ‘b’ respectively as shown in Figure 5. The 95% limits of agreement showed no statistically significant difference in measurements between two‐value and three‐value formula of RMPI in the ‘single‐image’ technique as shown in Figure 6. There was no statistically significant difference in heart rates measured from tricuspid and pulmonary waveforms in ‘dual image’ (P = 1.0) with mean difference of 5.3 bpm (95% CI 4.6–5.9). Similarly, there was no statistically significant difference between heart rate measured in ‘dual‐image’ and ‘single‐image’ techniques (P = 0.47) with mean difference of 3.4 (95% CI 2.9–3.9).

Figure 5.

Bland Altman Method of agreement between two techniques; ‘double image’ and ‘single image’ for right Modified Myocardial Index (RMPI), ‘a’ time interval, and ‘b’ time interval. The mean of the differences and 95% limits of agreement are quoted.

Figure 6.

Bland Altman Method of agreement between two methods of calculation of ‘single‐image’ right Modified Myocardial Index (RMPI); the two‐value (a–b/b) and three‐value (ICT+IRT/ET)formulas. The mean of the differences and 95% limits of agreement are quoted. ‘a’, tricuspid cessation to onset of flow; ‘b’ or (ET) intervals, the ejection (pulmonary) time; ICT, isovolumetric contraction time; IRT, isovolumetric relaxation time.

Discussion

The fetus is right heart dominant, thus the earliest signs of myocardial dysfunction may be observed in the right side of the heart.25, 26 However, the majority of fetal MPI publications have focused on the LMPI, most likely due to its assumed relative ease of acquisition. The rationale behind having RMPI measured in two Doppler waveforms was the anatomical location of tricuspid and pulmonary valves. It has previously been stated that RMPI could only be obtained in one Doppler wave form up to 20 weeks of gestation27 although this was not supported by other studies. A growing body of publications is now evaluating the RMPI, although most have used two waveforms, removing a proposed benefit of the MPI of concordant time intervals. Both single and dual Doppler waveforms have been used in early gestation.28, 29, 30 Turan et al. reported measuring RMPI in single Doppler waveform without difficulty in the studied fetuses at 11–14 weeks’ gestation.30 This is the first study demonstrating the feasibility of obtaining RMPI in a single Doppler waveform in the second and early third trimester, with acquisition rate only dropping significantly from 90% at 26 weeks’ to 76.5% at 27 weeks’ gestation.

The gestational period of 16–28 weeks was selected because it includes the gestational window where fetal surveillance may be particularly indicated in cases of twin‐twin transfusion syndrome31 where fetal cardiac dysfunction in the recipient twin incorporated in some staging system.32 The single‐image technique (ICT+IRT/ET) may reduce the time required for data acquisition, and gives valuable information on the separate related contraction and relaxation components. The observed limits of agreement of RMPI in Bland Altman plots between the ‘dual image’ and ‘single image’ (95% LA, −0.13 to 0.18) is probably not clinically acceptable if we expect subtle alterations (e.g. ±10–20%) in pathology.33

The almost identical repeatability of time intervals and calculated RMPI do not support the superiority of one technique over the other, although it is logical that ‘single image’ is more appropriate to use because it has been taken from a single cardiac cycle, and additionally reflects the established method of measuring the LMPI. The difference in mean values may represent overestimation of ejection time in the ‘dual‐image’ technique, which should be taken into consideration clinically if only this can be obtained. In this study, we eliminated two important factors in the calculation of right MPI; the effect of heart rate in measuring two different cardiac cycles and the possible effect of measurement error when three‐value formula is used. The observed overestimation of ejection time in the ‘dual‐image’ technique, in the presence of fixed machine settings, may highlight the effect of angle of insonation as this is the only machine setting that altered between these methods, and has previously been reported to alter the value of calculated MPI.34

Conclusion

Translation of the MPI into clinical practice has been limited by methodological inconsistencies.33, 34 As techniques move towards automation of the MPI,35 a single system to automate both single waveform LMPI and RMPI may further improve reproducibility. We have recently developed and reported an automation system for LMPI with perfect reproducibility (ICC 1.00),36 and the potential for comparable results using the single‐image RMPI is encouraging. The two image technique for RMPI was simply introduced to overcome a deficiency that we do not believe to be present during the gestational window of surveillance for TTTS (16–26 weeks). We recommend that where possible the single‐image technique should be used in order to improve consistency, and for comparison with the LMPI. If the dual‐image technique is used for the reason that the single image cannot be acquired it is important to note that this may generate different results, and different reference ranges may need to be generated accordingly.