This study has quantified the longitudinal, septal and lateral contribution to SV in patients with PH. We found decreased longitudinal contribution to SV in the left ventricle and unchanged contribution in the right ventricle. The LV lateral contribution to SV was increased, possibly as a compensatory mechanism to the decreased longitudinal function. Septal contribution to LVSV showed a tendency to be lower in patients compared to healthy controls. These changes in patients with a pressure loaded RV differ from previous findings in patients with volume loaded RV. Therefore, volume and pressure load of the right side of the heart yield different pumping physiology in both the right as well as the left ventricle.
The results indicate that in the pressure loaded RV, there is not only an interventricular dependency, but also an intraventricular compensatory mechanism, that is changed compared to healthy controls. We might therefore be able to detect a more subtle deterioration of the RV function and this may be used to follow patients on an individual basis.
This study has hereby shown that LV regional pumping modes are affected in patients with PH, even when global systolic LV function is unaffected.
Relation to earlier studies
With the principle of the muscle mass being constant throughout the heart cycle, both epicardial and endocardial contours have been validated to be applicable for SV calculations using CMR [
7]. Since the outer contour of the whole heart changes minimally through the heart cycle, the lateral contribution to SV has been distinguished by the measurement of the epicardial and not the endocardial volume change from CMR [
7,
10]. The wall thickening from the longitudinal displacement will affect the measurement of the lateral contribution, if measured from the endocardium wall or from the midwall. Endocardial change is therefore not equal to lateral function, but to a high extent a result of the AVPD and hence thickening of the wall. The myocardium has to thicken in the shorter ventricle, even without any radial squeezing movement [
7,
10]. In other words, even with no radial contribution to SV, there will still be an inward motion of the endocardium. This explains why we use the epicardial contour of the ventricle to calculate the longitudinal and lateral contributions to SV [
7,
10].
The AVPD, and thus longitudinal function, were in absolute numbers smaller in PH patients on both the right and left side compared to the control group. As previously shown using speckle-tracking strain from echocardiography, deterioration of the longitudinal RV function is associated with poor outcome [
18]. Similarly, a decrease in tricuspid annular plane systolic excursion has been shown with echocardiography in PH patients as having prognostic value [
19,
20]. Our findings are in concordance with these previous studies and also a recent study by Swift et al. on longitudinal and transverse RV function in PH with CMR [
21]. Swift et al. showed, that tricuspid annular plane systolic excursion was lower in patients with elevated pulmonary pressure [
21]. When the right ventricle dilates and the septum protrudes into the LV cavity, the LV cavity becomes small and compressed by the large right ventricle [
22]. The RV gets a more spherical appearance, resembling that of a normal left ventricle and the longitudinal muscle fibers change direction to a more circumferential direction [
23].
Interestingly, the decreased absolute AV-plane displacement in PH patients did not cause a decrease in longitudinal contribution to RVSV (RVSV
long%), as would have been expected. This was due to the increased RV area caused by RV dilatation and the decreased SV. Similar mechanisms have been shown in patients with LV heart failure, where AVPD is decreased and LV short-axis area increased, thereby preserving longitudinal pump function [
8].
LVSV
long% was lower in the PH population compared to healthy subjects, and an increased LVSV
lat% compensated for the decreased LV AVPD. This is in line with the reduced longitudinal speckle-tracking strain values with echocardiography in PH patients with normal systolic function [
12].
Septal movement contributed mainly to LVSV in systole (positive value of SV
sept%) in both PH patients and controls, though with a large range in the PH patients. Where the septum is convex in the healthy subjects, it is flattened or even concave into the LV in the PH patients, giving the RV a more spherical appearance, resembling a left ventricle [
21,
23]. These studies by Swift et al. and Grapsa et al. [
21,
23] as well as the study by Mauritz et al. [
24] have reported that changes in regional diameter, sphericity index from diameter or other two-dimensional regional measurements carry prognostic information of poor outcome. They suggest that the contributions to transverse and longitudinal motion using three-dimensional imaging may improve accuracy. Structures can translate out of plane, giving rise to risk of false shortening or lengthening, which is a challenge to take into account for in two-dimensional images. Swift et al. proposed that longitudinal and transverse motion in one plane may therefore not fully represent the relative contributions to RV function [
21]. In our study, we have used a three-dimensional approach to calculate regional contributions to SV and do not approximate regional function from two-dimensional image planes.
Comparison between pressure and volume loaded right ventricles
In patients with pulmonary regurgitation and volume loaded right ventricles, the septum moves paradoxically to the right in systole contributing to RVSV [
25]. In diastole the septal shape is flattened [
11,
13,
26]. Patients with PH, on the other hand, have pressure loaded right ventricles resulting in RV hypertrophy, paradoxical septal movement and a “flattening” of the septal shape in systole [
23,
25].
In our population of PH patients, the septum moved mainly towards the left ventricle in systole, though interestingly, with an impaired LVSV
long% and there is increased LVSV
lat%. The septal contribution differs from patients with volume loaded RV such as patients with pulmonary regurgitation or atrial septal defects where the septum moves towards the right side in systole [
11,
13,
25,
26]. The movement of septum towards the left in our study is in concordance with earlier studies with pressure loaded RV [
16,
27‐
29]. SV
long% was decreased on the left side in patients with PH compared to controls, but did not differ on the right side between patients and controls (Table
3; Fig.
4). This result also differs from the volume loaded RV due to pulmonary regurgitation where the LVSV
long% is mainly unchanged [
11] but the contribution of the LV lateral wall even more increased (58 ± 13 %) to compensate for the paradoxical septal movement [
11]. The RVSV
long% is on the other hand lower in volume loaded RV, due to pulmonary regurgitation, compared to healthy subjects and is compensated with an increased RVSV
lat%.
There could be several mechanisms to explain these differences. One explanation could be that the LV is volume depleted in PH patients and cannot be “filled out”, especially when the pressure is severely raised on the right side [
30]. Several studies have shown that the LV function is impaired despite preserved LVEF in PH patients [
12,
15,
16,
31,
32] and some studies have suggested that this could be caused by impaired LV filling rather than a “true” diastolic dysfunction [
15,
30,
32]. The contractile function and the cross sectional area of LV cardiomyocytes is substantially reduced in PH patients, which would support a true regional dysfunction [
33]. In that relation, the lack of prestretch of the LV due to volume depletion could be a contributing factor to the contractile function of the myocytes. Also, LV afterload can have an impact on the LV longitudinal and diastolic function, yet in our material the systemic blood pressures did not differ substantially between the groups. The decreased cardiac index and preserved LVEF in our study support the hypothesis of LV volume depletion. Of note, the cardiac index was lower in the PH patients compared to the previously studied patients with volume loaded RVs [
11]. Another reason could be the RV hypertrophy in patients with PH [right ventricular mass index (RVMI), 32 ± 16 g/m
2] compared to healthy subjects and to patients with volume loaded RVs (RVMI, 22 ± 15 g/m
2, previously unpublished data) [
11]. The RV hypertrophy in our study is in concordance with earlier studies [
6,
34]. This suggests, that the remodeling of the RV in PH patients may differ compared to patients with volume loaded RVs. We have included a regression analysis between RV ventricular mass and the regional contributions to SV on both sides. We found no correlations, neither linear nor non-linear but this needs to be further tested in larger patient cohorts.
RV intraventricular compensation
In the PH patients the range of both RVSV
long% and SV
sept% are wide and encompasses extremes such as e.g. RVSV
long% of 114 % compensating for a SV
sept% of 19 % (septal movement towards the left) in one patient (Table
3). When the septum contributes the most to the LV, the septum is bulging concave into the left ventricle in systole in patients with PH. To compensate for the negative contribution to RVSV, RVSV
long% can be even greater than the total RVSV. On the other hand, when RVSV
long% decreases in PH patients, RVSV
lat% increases, and exceeds the lateral contribution in healthy controls (Fig.
6). As such, when one part of the RV function is altered another takes over. This could indicate that in the pressure loaded RV there is not only an interventricular dependency but also an intricate intraventricular compensatory mechanism. Since this shift can be quantified instead of approximated, it is now possible to follow patients on an individual basis and thus we might be able to detect more subtle deterioration of the RV function. If there are prognostic implications of these measures of ventricular function remains to be investigated.
Limitations
The genesis of PH is, in our study, somewhat heterogeneous with a variation of different levels of pulmonary arterial pressure, RV hypertrophy and RVSV. Yet all patients had precapillary PH. It has been suggested that the genesis of PH may lead to diverse remodeling of RV [
27,
35]. Our study was not designed to accommodate a differentiation of these factors.
The age difference between controls and patients may be considered a limitation in the study. In a posthoc analysis of the healthy control group, we found an inverse correlation between RV AVPD and age (r = −0.39, p = 0.02), but no correlation between LV AVPD and age (p = 0.15). On the other hand, when correlating the different regional contributions to SV to age, there was no significance in any of the measures. Furthermore, we found no difference in regional contributions in healthy controls >50 years compared to those <50 years. Therefore, age does not appear to influence the results of the regional contribution to SV. The sample size of this proof of concept study is small and inclusion was retrospective. Therefore, the new findings of this study need to be tested in larger patient cohorts to show the relationship with clinical outcome measures.