This study demonstrates that the MPI for the RV and LV can be measured reliably in children with IPAH with acceptable reproducibility. We found that RV MPI is elevated in pediatric patients with IPAH compared with age-matched control subjects. Importantly, among patients with IPAH, RV MPI correlated with invasive measurements of MPAP and trends in RV MPI correlated with trends in MPAP. These findings support the value of MPI in the clinical monitoring of these patients. The advantages of MPI over TR velocity are 2-fold: (1) not all patients with pulmonary hypertension have sufficient TR for accurate measurement of the peak jet; and (2) MPI appears to correlate with MPAP, which was chosen to define this disease because it is more reliable than the peak instantaneous PA pressure derived from the TR jet velocity.1
In adults with IPAH, RV MPI has been shown to predict outcome.18,19
It is useful in assessing the effects of prostacyclin therapy.20
Our findings correspond to the experimental study by Sugiura et al21
who demonstrated a significant positive linear correlation between the RV MPI and changes in MPAP in neonatal piglets with hypoxic pulmonary hypertension. Other studies have shown that the MPI correlates with invasive measures of both RV and LV function22,23
and is useful in the follow-up of patients with cardiomyopathy.24,25
Studies in children with RV volume and pressure overload have demonstrated the feasibility of measuring this index in the pediatric age group.26,27
The use of time intervals to detect and monitor pulmonary hypertension is well established28
and particularly useful because they are not limited by the geometric shape of the ventricle, a fact that is important in these patients who usually have distorted ventricular geometry. Several studies have documented the use of the pre-ejection period, ET, and acceleration time for patients with pulmonary hypertension.29–31
The MPI also includes changes of the IVRT, a diastolic time interval. The systolic and diastolic time intervals are easily obtained by routine Doppler techniques during standard echocardiographic examination and are simple to measure, with excellent reproducibility. In addition, MPI is independent of heart rate.32
All patients in this study who had an improvement in MPAP of 20% or more in response to vasodilator therapy also had an improvement in RV MPI. One patient with severe elevation of PA pressure had a decrease in MPAP of 18% between initial and follow-up catheterization, without an improvement of the RV MPI. A possible explanation could be permanent loss of RV function secondary to the severe pulmonary hypertension and chronic high afterload. In this case, the reduction in MPAP could be the result of remodeling in the pulmonary vasculature whereas the MPI could reflect persistent RV dysfunction. Our data cannot answer the question of how right bundle branch block would affect this marker because none of the patients had significant RV conduction delay.
The relationship of RV MPI to ventricular loading conditions remains unclear. Eidem et al26
demonstrated that RV MPI was increased for patients with combined pressure and volume overload, and did not change after intervention to relieve the volume overload. In addition, data from a porcine model also supported relative load independence of this index.33
However, more recently, Cheung et al34
presented experimental data to suggest significant alterations of the MPI in response to acute changes of ventricular loading conditions. In light of these data, it is possible that the abnormal RV MPI in our children with pulmonary hypertension at least in part reflected altered RV afterload. It has been difficult to study the response of the RV to changes in loading conditions although it is clear that it is significantly different from that of the LV.35
In children, the noninvasive quantitation of RV function has been particularly difficult because magnetic resonance imaging often requires general anesthesia and radionuclide studies are hindered by the need for sedation, limited resolution, and radiation exposure.36–38
Our data support that the RV MPI is a sensitive tool to estimate MPAP in children with IPAH and to monitor response to therapy. No conclusions can be made regarding the role of RV dysfunction in our observations. Further studies with longer follow-up periods will be beneficial to further delineate the use of MPI in predicting prognosis in pediatric patients with IPAH.
The primary limitation of this study is the small size of the study group. However, the population is highly selected to patients with IPAH, without other disease. Another limitation is the fact that the follow-up catheterizations were performed at different times after initiation of vasodilator therapy. The RV MPI appears to agree well with changes in MPAP for both responders and nonresponders but, because the relatively short follow-up time and the small number of patients, no comment can be made regarding the possible role of ventricular remodeling on MPI measurements.
The MPI provides an easily obtainable and noninvasive tool for monitoring MPAP in pediatric IPAH. RV MPI is independent of quantity of TR and can be especially useful in those children without measurable TR. We propose that RV MPI may be a useful adjunct in the clinical assessment of pediatric patients with IPAH.