Since conventional echocardiography explores mainly the longitudinal component of RV systolic function, there was no comprehensive method to evaluate the relative contribution of the different components of RV wall motion (e.g. longitudinal, radial and anteroposterior) to global RVEF. Thus, to our knowledge, this is the first study to assess 3DTE-derived global and regional RV mechanics in rToF patients with severe pulmonary regurgitation and their relations with RV pump function. According to our results: i) rToF patients had lower global RVEF compared to age- and sex-matched controls; ii) in terms of the relative contribution to global RVEF, only the longitudinal component of RV wall motion was reduced in rToF, whereas the radial and antero-posterior components were similar between rToF and controls; iii) rToF patients had similar RV septum, free-wall apical and mid segment 3D circumferential strain values, but significantly lower circumferential strain in the basal RV free wall segment; iv) RV 3D longitudinal strain values were reduced in the RV free wall segments in rToF, but they were similar to controls in the septum.
RV function and mechanics in rToF patients
Recent studies demonstrated that longitudinal RV deformation is decreased in rToF with pulmonary regurgitation as a sequel [3, 20]. In addition, the deterioration of RV longitudinal strain has been found in rToF patients with maintained RVEF [3], suggesting that probably other wall motion components maintain the global RV function. However, despite the notable amount of circumferentially oriented myofibers in the subepicardial layer of the RV myocardium [21] and the complex RV contraction pattern[7], data about the non-longitudinal shortening of the chamber in rToF patients are scarce. Similar to the findings of Stephensen et al. [22], we found that in rToF patients with RV volume overload the longitudinal component of RV wall motion is impaired more than the radial one. According to our results, in comparison with the controls, the rToF patients had preserved the relative contribution of the radial (the so-called “bellows effect”) and anteroposterior motions to global RVEF, but significantly lower longitudinal shortening contribution to RVEF. Considering the decreased global RVEF in rTof patients, we can conclude that the radial and anteroposterior RV wall motion components have a higher impact to global RVEF in these patients. Thus, this could explain the phenomenon in clinical practice why some rToF patients with reduced TAPSE still have maintained global RVEF.
Furthermore, we demonstrated, that in rToF patients, the radial and anteroposterior components of ejection fraction showed better correlation with global 3D RVEF than the longitudinal one. These findings also emphasize that parameters measuring the longitudinal contraction offer only a partial assessment of the global RV pump function in rToF patients. This is very important because, due to the large surface of RV free wall, even a small amplitude of inward movement of the RV free wall may have a significant effect on the global RV function [4]. However, despite the evidences of the importance of the radial RV motion in physiological conditions and in patients with different cardiovascular diseases [4, 18, 23, 24], there is no 2D RV functional parameter, which allows to selectively and sensitively assess the relative importance of the radial contraction of the RV. Parameters used in everyday clinical practice refer predominantly to the longitudinal shortening of the RV wall (TAPSE, RV free-wall s′ velocity by tissue Doppler imaging). Moreover, the widely used TAPSE is a one-dimensional and angle-dependent parameter [25], which measures the excursion of the tricuspid annulus towards a reference external to the heart and ignores the outlet portion and the septal contribution to RV ejection. Selly et al. also confirmed that TAPSE is not sensitive enough to evaluate RV systolic function in rToF patients, whereas FAC, which incorporates longitudinal and (partly) radial components of RV contraction, and of course, 3D RVEF seems to correlate well with cardiac magnetic resonance imaging-derived measurements [26]. However, FAC still represents the RV function in only a single 2D cut plane exploring a very limited amount of the RV myocardium. Moreover, suboptimal RV endocardial definition, especially in dilated and heavily trabeculated RVs, can further reduce its accuracy. Of note, FAC does not include the contribution of the RV outflow tract to ejection, which is very important in patients with surgically repaired ToF, and can result in an overestimation of the global RV function in this subset of patients [5].
Speckle-tracking echocardiography has been shown to be more sensitive than conventional measures in detecting changes in myocardial function in rToF [27]. However, although 2D longitudinal strain is less load-dependent than conventional measures of RV function, it still explores the deformation of the myocardium in one direction only. In rToF patients, RV 2D longitudinal strain (measured from the apical four-chamber view) showed only a weak correlation with RVEF [28]. Accordingly, in our rToF patients, RV 2D global and septal LS had a weak to moderate correlation with RVEF, but RV free wall LS did not show a significant correlation with RVEF. This is probably related to measuring only the inlet and trabecular parts of the RV, and also the fact that radial/anteroposterior RV shortening is not taken into account. Estimating the RV circumferential strain in 2D requires a short axis view, which is difficult to obtain in adults. 3DTE allows us to encompass the entire RV in a single pyramidal dataset and perform a detailed quantitative analysis of its size and function providing a good correlation with RV volumes and ejection fraction measured by cardiac magnetic resonance [8]. Compared with 2D strains, 3D analysis is not slice-plane limited, delivers vectored data in 3 orthogonal planes from one single dataset and given the complex anatomy of the RV, may better reflect the true pattern of RV contraction. Recently, Moceri et al. [29] demonstrated that rToF patients with chronic RV volume overload had lower RV 3D global longitudinal (the inlet septum and superior part of the free wall were preserved) and circumferential (the infundibular, membranous and inlet septum were preserved) strain compared with controls. Accordingly, we also found that in rToF patients with severe pulmonary regurgitation RV 3D global longitudinal and circumferential (summation of radial and anteroposterior motions) strain were reduced compared with controls. However, according to our data, looking at the regional RV deformation, rToF patients had similar RV septum, free wall apical and mid segment CS values, and lower CS only in the basal RV free-wall segment. We hypothesize that these findings may explain the preserved RVEF in the apical region demonstrated by Van Der Hulst et al [30]. Moreover, we found that RV LS was reduced in the RV free wall segments in rToF, but it was similar to controls in the septum. Finally, we showed that 3D LS had better correlation with the LEF and global RVEF compared with 2D strain, in rToF patients.
The RV anteroposterior shortening is even more neglected in daily clinical practice, thus, data about this component of global RVEF are highly limited. We hypothesize that RV anteroposterior shortening may reflect the left ventricular contraction’s contribution to overall RV function by stretching the RV free wall insertion lines over the interventricular septum. Recently, Lakatos et al. demonstrated comparable RV AEF values between heart transplant recipients and healthy control subjects, and also between elite athletes and sedentary individuals [18, 19]. According to our results, the relative contribution of AEF to global RVEF in rToF was similar to controls. The common feature of both rToF and controls is that the left ventricular function was preserved, which could be related to the maintained anteroposterior RV shortening.
There are several underlying mechanisms which may explain the RV mechanical remodeling we observed in rToF patients with severe pulmonary regurgitation. First, according to the Frank-Starling law, when preload increases and the RV dilates, the contractile function increases and, for some time, effectively compensates the altered hemodynamic conditions. However, long-term chronic RV volume overload leads to stretching of myofibers with subsequent distorted meshwork, more spherical architecture and re-alignment of myocardial fibers that might modify the contraction pattern to a greater radial contribution [22, 31]. Previous studies also suggest another possible explanation for mechanical remodeling in rToF patients. Compared to healthy individuals, ToF patients have a prominent middle layer with circumferentially oriented myofibers, which resembles the left ventricular architecture [32]. Moreover, it was shown that global and regional RV myocardial deformation was affected differently by chronic volume loading in patients with atrial septal defect compared to ToF patients [29, 33]. Data exist on the improvement of longitudinal strain after percutaneous pulmonary valve replacement in ToF patients [27, 34]. Thus, future studies are needed to determine whether these changes in myofiber architecture and subsequently in the mechanical pattern are inherited or just consequences of chronic volume overload of the chamber.
Limitations
The application of the ReVISION method relies on accurately generated 3D endocardial surface model and therefore, it is dependent on the quality of the 3DTE images. Moreover, in rToF, the acquisition of good 3D datasets could be hampered by a markedly dilated RV. However, experience in 3D acquisition and analysis might minimize this limitation. Nevertheless, ReVISION method assess RV mechanics in a fully automated manner and does not add further variability to that associated with 3D RV volumetric and functional evaluation.
Strain measurements based on 3D analysis cannot be compared with measurements performed using commercially available 2D methods. Moreover, the absence of a true reference method to test the accuracy of our measurements could be considered as a limitation of this study, and only prospective outcome studies can assess the clinical value of our approach.