The concept of RVSWI
RVSWI is the product of measured mRAP, mPAP and SV derived from RHC. Consequently, RVWSI incorporates elements of RV preload, afterload as well as contractile performance [
8]. Previous studies have suggested that RVSWI could be used as a marker of clinical outcome since it reflects total RV workload [
19,
20]. In patients who have undergone lung transplantation, a higher RVSWI predicted worse outcomes [
19]. RVSWI has also been used in patients with severe left ventricular heart failure eligible for left ventricular assist device to determine if the RV is sufficiently strong to meet the demands of the left ventricle and if a supplementary RV assist-device is necessary [
20]. In this setting a cut-off value for RVSWI ≤ 250 mmHg x mL/m
2 is associated with a need of RV assist-device.
The role of RVSWI in patients with PAH is still an unexplored field. In children as well as in adults with PAH, RVSWI has, however, shown a prognostic value [
8‐
10] but data are sparse.
The interpretation of RVSWI is however complicated and general cut off values for RVSWI has not been established. Initially, a high RVSWI indicates an increased workload of the RV, required as it strives to overcome an increased pulmonary vascular stiffness [
21]. Clinically this is demonstrated in the early stages of PAH, whereas the RV can adapt physiologically with hypertrophy and increased contractility but without significant changes in size [
22]. In the progress of the disease, RV dilatation occurs as a compensatory mechanism to maintain an adequate SV [
22]. Theoretically, in this stage RVSWI reaches its plateau phase. Eventually, with a continuous rise in PVR, these compensatory mechanisms are inadequate resulting in progressive impairment in RV contractility and consequently a decrease in both SV and mPAP [
22]. In this scenario RVSWI decreases. However, in clinical practice, specific drug therapy is initiated in the majority of patients diagnosed with PAH [
11]. In this scenario, if the patient responds to treatment, RVSWI is affected due to a decrease in mPAP and an increase of SV. Nevertheless, since no reference values has been established, comparison of absolute RVSWI values between patients is challenging. Therefore, in clinical practice, the role of RVSWI may be best suited in follow-up assessments where the patients are their own reference. Even if the clinical use of RVSWI in this setting seems to be a promising tool it requires a RHC.
Echocardiographic calculated RVSWI
Finding new ways to noninvasively assess RV function in patients with PAH is of great importance. Although echocardiographic assessment of the RV has several limitations owing to its complex geometry, which challenges clinicians in daily practice, it is still the preferred imaging modality in daily routine. In this study we examined four different methods for non-invasive calculations of RVSWI using echocardiography-derived SV, pulmonary pressures and mRAP.
SV may be derived from either RVOT, or from LVOT. Unless there is intracardiac shunting or regurgitation of one or both semilunar valves present the SV may be considered equal. Since SV calculated from RVOT has several pitfalls, especially measuring the RVOT diameter [
23], we used measurements from LVOT. In our study none of the patients had intra cardiac shunts or an aortic- or pulmonary regurgitation. Consequently, SV calculated from LVOT was considered equal to SV calculated from RVOT in this study.
Using echocardiography, calculation of systolic and mean pulmonary arterial pressure can be estimated from the spectral doppler of an existing tricuspid regurgitation. In two of the methods (RVSWI
ECHO-1 and RVSWI
ECHO-2), the TR
maxPG was used since it is an established non-invasive method for estimation of systolic pulmonary arterial pressures. The advantage using TR
maxPG compared to the mean gradient is the accessibility since it is present in most PAH patients and easy to obtain. By echocardiography mPAP can be assessed in several ways [
4]. In this study the velocity integral was used in two of the methods (RVSWI
ECHO-3 and RVSWI
ECHO-4) since it has proven to exhibit a value closer to mPAP by RHC than the other methods [
24,
25]. For the echocardiographic measurements using TR
maxPG (RVSWI
ECHO-1 and RVSWI
ECHO-2) a strong correlation to RVSWI
RHC were demonstrated, but poor agreement to the absolute values with large biases to be addressed. Incorporation of mRAP (RVSWI
ECHO-2) did not change the results. This is in alignment with a study in children with PAH, where mRAP were not included, and a similar correlation was demonstrated [
7].
For the echocardiographic measurement using TR
meanPG, (RVSWI
ECHO-3 and RVSWI
ECHO-4, respectively) a moderate correlation to RVSWI
RHC were demonstrated. The method using only mPAP (RVSWI
ECHO-3) showed no difference in absolute values compared to RVSWI
RHC. Therefore, incorporation of echocardiographic estimated mRAP using IVC had no incremental value in non-invasive calculation of RVSWI
ECHO, probably due to its poor accuracy in the clinical settings [
26]. In comparison to RHC, none of the echocardiographically derived methods could demonstrate both good correlation and high agreement in absolute values. The differences between invasively and echocardiographic derived RVSWI could also be explained by errors from both modalities.
By echocardiography, potential sources or error consist of inaccuracy in calculating SV as well as the pulmonary pressures. Concerning SV, measuring the diameter from an outflow tract has well known limitations. Calculations of LVOT-flow and TR-gradient are Doppler-derived. Thus, they both are angle dependent which can lead to underestimation. Moreover, overestimation must be avoided by ensuring that measurements are performed only on well-defined spectral curve. Another source of bias in measurements of pulmonary pressures between the methods is estimation of mRAP by echocardiography which consequently could lead to disagreement. Concerning RHC, thermodilution can overestimate SV, especially in low cardiac output states. Moreover, pressure calculations by RHC are dependent on correct calibration and could be affected by respiration and arrhythmias.
However, the results suggest that either RVSWIECHO-1 could be the preferred method according to its level of correlation or RVSWIECHO-3 according to its better agreement with RHC. One major drawback of RVSWI is to identify if a decrease in RVSWI is due to treatment response (lower mPAP) or RV failure since both results in a decrease in TR pressure gradient. Additional clinical parameters, such as 6-min walk test, NT-proBNP, echocardiographic RV function parameters or changes in SVI, could be considered for differentiation.
Clinical implications
In our PAH-clinic, we routinely perform serial echocardiographic evaluations, right heart catheterizations and clinical assessments in combination with 6-min walk tests according to ESC:RRS risk stratification [
11]. Even if conventional echocardiographic parameters (i.e. TAPSE, RVFAC and RVFWS) have an established role in the clinical assessment of RV function, they have not been implemented in the risk assessment algorithm in PAH [
11]. In the clinical setting it is of great importance to early identify a failing RV in order to in a timely manner determine when the patient needs to be listed for lung transplantation. Consequently, an exploration to identify useful echocardiography-derived measurements besides RA area and the presence of pericardial effusion are warranted. RVSWI measured by echocardiography could be a new method for prognosis assessment in adult patients with PAH preferable for follow-up in selected cases where the patients are their own reference. However, it is highly unclear at present whether echocardiographically derived RVSWI have additive value in these patients. Certainly, more studies are needed to understand the clinical implication on how to interpret RVSWI
ECHO and its role in management of these patients.
Limitations
There are some limitations to our study. The use of invasively measured RVSWI for estimation of prognosis in PAH patients is not fully explored, which makes the utility of echocardiographically RVSWI also unclear. Consequently, the results of this study should merely be described as a proof of concept study.
The number of patients is furthermore relatively small. However, PAH is a rare disease and it is therefore difficult to obtain large study cohorts. Echocardiography and RHC were not performed simultaneously. However, most patients had examinations the same day or the following day with no medical changes. Even though the delay was minimal, this could have influenced the result.
Systemic blood pressure was only obtained invasively and not in conjunction to the echocardiographic examination that could to some extent have affected the results.
A concern is that our study estimated CO from the LVOT considering it equal to CO from the RVOT. However, in the presence of a severe tricuspid regurgitation, the RV-workload could increase. Thus, RVSWI would be inaccurate. Our study population comprised patients with mainly mild tricuspid regurgitation and none with more than moderate TR. Moreover, SVI calculated by echocardiography and by RHC were similar. This is despite the fact that moderate or severe tricuspid regurgitation is associated with underestimation of cardiac output measured by thermodilution [
27], further exacerbating any difference. We therefore conclude that this issue did not affect the present study, but feel that the validity of derived calculation will lose accuracy and validity in the presence of severe TR.
By echocardiography, CO derived from RVOT measurement is challenging in most patients and have well known limitations in clinical practice [
28].