This study represents the first attempt to assess human fetal systolic electromechanics using simultaneous fMCG and pulsed Doppler ultrasound. fMCG is a promising new technique for assessing fetal rhythm [15
]; however, no prior studies have utilized fMCG to evaluate human fetal electromechanical physiology, despite the fact that these cardiac parameters are routinely evaluated in the neonate, child, and adult with heart disease. The high signal-to-noise ratio of fMCG allowed us to study subjects over a much wider range of gestational ages, compared to most prior studies. The high precision afforded by pulsed Doppler ultrasound in combination with fMCG allowed us to obtain serial measurements with good session-to-session consistency and in many cases to resolve beat-to-beat correlations.
Although the mean PEP obtained from flow onset and valve clicks were in excellent agreement, valve clicks can be detected with greater temporal precision than flow velocity onset, evidenced by standard deviations of 4.5 and 6.3 ms, respectively. Valve clicks, therefore, may provide more precise estimates of mechanical, as well as electromechanical, intervals. This is notable because typically valve clicks are not utilized in routine clinical echocardiographic scanning nor in tissue Doppler.
Our measurement of PEP/ET (0.36 ± 0.01) in the fetus is in excellent agreement with that of the neonate and adult. In the adult, this ratio was found to be 0.345 by Garrard et al. [17
], and in newborns a value of 0.350 has been calculated [18
]. The correlation between this ratio and gestational age is also stronger than that of PEP and gestational age. According to Levy et al. [18
], PEP/ET has been found to be an excellent index of function by virtue of its correlation with ejection fraction and its inherent characteristics of partially nullifying heart rate variability; thus it may have greater clinical utility than PEP alone.
Positive correlations between PEP and gestational age, and PEP and QRS width, were seen here, consistent with several earlier studies [9
]. These trends were apparent within individual subjects, demonstrating the precision of our measurements. A proposed explanation for the increasing PEP with gestational age is the increase in myocardial mass and the concomitant prolongation of ventricular depolarization (fig. ) [9
While most systolic time intervals increase with gestational age, it is notable that ejection time did not increase and in fact showed a decrease that was not statistically significant (fig. ). In particular, while onset of ventricular ejection is progressively delayed, reflected in the lengthening of PEP, ejection time stays the same or decreases, comprising a smaller fraction of the cardiac cycle, despite the fact that stroke volume continually increases during gestation.
Across sessions, PEP was found to correlate positively with RR [7
]. On a beat-to-beat basis, however, an inverse relationship between PEP and the preceding RR was seen. The observed beat-to-beat correlations between PEP and RR, and between ejection time and RR (fig. ), are compatible with the influence of ventricular filling on stroke volume and contractility predicted by the Frank-Starling mechanism. Although stroke volume was not measured in this study, it has been shown to correlate positively with ejection time [20
]. Enhanced contractility also implies that ventricular pressure develops more rapidly, implying a negative correlation between PEP and RR interval, as observed here. The positive correlation between PEP and RR, seen in 2 subjects with higher heart rates and/or reduced ejection time, may have reflected a change in autonomic or blood flow state.
Study of fetuses with abnormal heart rates, arrhythmia, and ion-channel defects are currently underway. We are optimistic that assessment of fetal systolic electromechanical function via fMCG and echocardiography will provide a better understanding of the underlying processes that lead to poor systolic cardiac function and heart failure in the at-risk human fetus.