We present, to our knowledge, the first study of TA and TV morphology assessed by CMR combined with additional invasive hemodynamic assessment in patients with severe PH due to chronic pulmonary thromboembolism during 12 months follow-up after PEA. We also provide CMR data on TA and TV morphology in normal subjects.
The main findings were as follows: Firstly, significant changes of TV morphology, noted as leaflet area, tenting volume and tenting height in systole, were significantly reduced but TV parameters were comparable to control subjects after 12 months following PEA; secondly the TA size by circumference and area were without significant changes and were comparable to control subjects. However, the shape of the TA did change significantly as the annulus circularity index (SL/AP-ratio) decreased; thirdly, the TA height in systole decreased significantly and reached comparable values as compared to control subjects; fourthly, the changes to TV morphology expressed by leaflet area, tenting volume and tenting height in systole was significantly and negatively correlated to the changes in RV-PA coupling; finally, as expected significant RV and RA remodeling and improvement of RV systolic function were noted after PEA but the changes to RV and RA dimensions or volumes did not correlate to the changes of the TV morphology observed.
Preoperatively 40 % of our patients demonstrated a moderate-severe functional TR in accordance with observations in PH in which severe TR varies between 10–30 % of cases [2, 17]. As expected we also noted a significant reduction of moderate-severe TR with the presence of only 10 % after 12 months following PEA in accordance with a previous study [8]. Tenting height is reported to be increased in TR with different etiology of PH as demonstrated by Topilsky et al. who reported a tenting height of 8.0 mm assessed by transthoracic 2D echocardiography [18]. The preoperative tenting height was significantly increased to an average of 11.4 mm by CMR (average normal subjects 7.0 mm) which normalized with a height of 7.0 mm after 12 months following PEA. In the present study, the tenting volume of the TV was increased nearly 3-fold preoperatively compared to controls (1.5 cm3) but normalized at follow-up. Increased tenting volume has been reported in patients with functional TR in two previous 3D echocardiographic studies showing a tenting volume of 4.2 cm3 in 17 chronic PH patients with significant TR and of 3.2 cm3 among 53 patients with severe TR and PH of different etiology, respectively [19, 20]. Despite different imaging techniques the tenting volume seems consistently to increase considerably in PH patients with functional TR independent of etiology. Preoperatively, we noted that the leaflet area was increased in systole to the same extent as demonstrated by Afilalo et al. in a study with patients with severe functional TR and PH. In the present study, the leaflet area was significantly decreased and normalized during follow-up17. The coaptation height did increase but insignificantly and remained lower than controls at follow-up. The changes in TV morphological parameters were significantly correlated to the changes of RV-PA coupling but was not directly correlated to changes of the annulus, shape nor RV volume or even the sphericity index. The tricuspid leaflet closure depends mainly on leaflet adaptation, tethering forces and annular morphology. Leaflet adaptation is abnormal before PEA but the adaptation seems to reverse to near normal conditions at follow-up. A dramatic RV remodeling was shown after PEA as RV volume, and the sphericity index normalized during follow-up. Dilatation and changes of RV geometry are known to affect the position and function of the papillary muscles (PM) resulting in increased tethering of the TV [21]. Distortion of the spatial relationships between the RV, PM and TV is likely to influence the presence of TR and the demonstrated changes of the TV morphology and function. However, the major determinants of TR severity have previously been investigated by 3D echocardiography showing that leaflet area, tenting volume and leaflet closure are independent predictors of TR whereas RV dilatation or echocardiographic Doppler estimated systolic pulmonary artery pressure was not [20]. In accordance with the present findings a previous study has shown that regression of TR in PH patients is associated to the changes of TV tethering with reduction in tenting height and area as the major determinants [6].
Previous two- and three-dimensional echocardiographic studies of functional TR in PH patients have reported various degree of TA dilation depending on the severity of the regurgitation [19–21].
Among the present patients no significant increase in annular area or circumference were noted and the annulus size was comparable to control subjects. One important reason for this finding could be that the TR severity of the present population was preoperatively only moderate and thereby contributing less to RA volume overload with subsequent dilatation of the RA as well as the annulus. The potential pathophysiological mechanism in the present patient population is likely to be initiated by the remodeling of the RV and tethering of the TV as seen in other etiologies of PH [19, 22]. In the PH population with TR the TA is often less dilated as compared to patients with secondary functional TR and chronic atrial fibrillation [23, 24]. Despite that the size of the TA seems to be less affected in the present study. Minor but significant changes were noted regarding the annular shape as annular circularity index was increased preoperatively as compared to controls. The minor changes observed in the TA in terms of base area and septal-lateral dimension were modest but significantly correlated to changes in systolic PAP, RV-PA coupling, RV end systolic volume and RA volume. Based on the present data a conservative approach with respect to tricuspid annuloplasty in CTEPH undergoing PEA even with a significant TR seems to be advisory. In patients undergoing left valve disease surgery - in particular mitral valve repair or replacement – tricuspid annuloplasty is recommended when the TA diameter ≥ 40 mm [25].
Preoperatively, our CMR data demonstrated classic RV remodeling as seen in PH with increased RV mass, severe RV dilatation, increased sphericity and impairment of systolic function in terms of reduced ejection fraction and stroke volume. During follow-up, extensive reverse remodeling was noted as RV mass and size were significantly reduced and normalized. However, the RV systolic function remained mildly impaired as compared to controls.
Beyond reporting serial data on RV volume and systolic function, we were able to measure and characterize the TA and TV morphology in CTEPH patients and normal subjects by CMR. The CMR technique seems promising for TV evaluation. The benefit of CMR in the initial diagnosis of CTEPH is probably limited. However, in terms of RV characterization CMR provides very accurate estimates of RV volumes, RV function and TV regurgitant volumes. In addition, LGE and T1-mapping will probably provide insights on RV damage among CTEPH patients in the near future.
In terms of medical treatment for CTEPH there is no clear support for treatment with specific PH active drugs before PEA. Furthermore, the only approved drug in CTEPH, riociguat, is only registered for use in inoperable cases or in persistent PH after PEA [26].
Some limitations have to be considered in the present study. First of all, the number of patients studied is small but the examinations were performed prospectively and consecutively combining CMR techniques with invasively assessed hemodynamic parameters during a complete one year of follow-up. Despite the small number of patients studied as compared to other observational studies of TR and TV in PH patients, we had the opportunity to study the valve morphology in a situation where the hemodynamic conditions were reversed and thereby being able to study the associations between RV remodeling, hemodynamic and morphological TV changes.
The number of PH patients with severe TR varies considerably in line with the present findings which limits the possibility to study to what extent the observed changes in TA and TV has on the patients with severe TR.