Key findings of our study: (1) Compared with TR Vmax and its derived parameters, sPAPECHO showed better sensitivity for predicting PH while maintaining similar specificity. (2) The accuracy of sPAPECHO could be affected by TR signal quality, PAWP and sPAPRHC level.
Performance of sPAPECHO in PH screening
In our study, sPAPECHO exhibited best correlation with sPAPRHC and was superior to TR Vmax and its derived methods in PH screening. sPAPECHO didn’t amplify measurement errors in assessing pulmonary artery pressure as a derived variables of TR Vmax as mentioned in the currents guideline, on the contrary, it showed better sensitivity while maintaining similar specificity. Moreover, sPAPECHO and mPAPECHO contain more information from RAP relative to TR-PG and TR-mPG which may accounts for their better accuracy and lower bias. In this cohort, the RAP was appropriately evaluated in 66.2% of cases (defined as RAP estimated by echocardiography was in the same range of RAP measured by RHC) ,13.9% were underestimated and 19.9% were overestimated. In addition, 76.2% (16/25) of cases whose RAP was overestimated make up for the underestimation of sPAPECHO to varying degrees. In 72.2% (57/79) of patients, sPAPECHO was overestimated not because of RAP, but the overrated TR-PG. This phenomenon demonstrated that RAP estimated by echocardiography is reliable and could add additional value in evaluating PAP. Hellenkamp’s study on mPAPECHO also supported RAP is of additional diagnostic value in predicting PH. But Venkateshvaran’s research suggested recommendation based RAP demonstrated poor precision and may not necessarily contribute to greater accuracy of pulmonary artery pressure estimates . Until now, there is no consensus on the role of RAP, but we can’t deny that elevated RAP is an important sign for PH. So further studies are needed to figure out those uncertainties and make RAP a more valuable parameter to evaluate PH.
Reasons for inaccuracy of sPAPECHO estimation
First, our finding confirmed previous reports that the TR signal quality is vital for accurate assessment of sPAPECHO. But previous studies also reported the accuracy of sPAPECHO would be affected by TR severity[5, 12]. So the relationship between TR severity and TR signal quality was further analyzed. In our cohort, the difference in TR signal quality between different TR severity was statistically significant (P＜0.05). For patients with severe TR, 81.2% of them had type A signal quality and sPAPECHO were evaluated appropriately in 61.9% of them. While for patients with mild or moderate TR, 54.8% of them obtained type A signal quality and 37.1% of them estimated sPAPECHO accurately. In this study, patients with severe TR seem to have a better chance to get complete signal quality and assess sPAPECHO properly. But TR severity didn’t include in the final equation. The possible explanations might be what truly determined the accuracy of sPAPECHO assessment is TR signal quality. Even with mild or moderate TR, as long as signal envelope is complete, accurate assessment could be achieved. Moreover, 9.6% of patients in our cohort had severe TR which is in line with the actual clinical situation that severe TR only appears in the minority of the total patients. On the whole, the impact of TR severity on the accuracy of sPAPECHO evaluation is not as significant as TR signal quality.
Thus, in order to avoid underestimation of sPAPRHC in clinical practice, it is necessary to perform multi-section and multi-angle measurement of echocardiographic images to obtain a more complete signal envelope, especially for patients with mild TR. And for patients without TR, mPAP estimated by pulmonary regurgitation is also a useful alternative for screening PH.
Second, our data also suggested patients with higher PAWP tended to underestimate sPAPRHC by DE. Finkelhor et al also found PAWP had a strong inverse correlation with the difference between sPAPRHC and sPAPECHO. They speculated that elevated left atrial pressure can be transmitted to the right atrium via the shared inter-atrial septum as well as through pericardial constraint and limit TR velocities, thus the accuracy of sPAPECHO will be affected. Even though the mechanism of how PAWP affects pulmonary artery pressure is still unclear, interestingly, more and more studies are beginning to notice this phenomenon. Amsallem et al found patients with higher PAWP is assosiated with lower sPAPECHO thresholds for PH diagnosis. Our results also supported this view, the optimal cut-off value of our cohort for determining PH was 55mmHg, which is much higher than previous studies. Patients with pre-capillary PH (85.8%) accounted for the majority of our population may explain this discrepancy. Patients with left heart diseases (post-capillary) PH took up for 84% and 76% in these two researches, respectively[1, 15]. This finding suggests that the best threshold of pre-capillary PH might be higher than post-capillary PH and PAWP may play an important role in it. Therefore, a higher threshold of sPAPECHO for determining pre-capillary PH is more appropriate.
Third, for the effect of sPAPRHC level on the accuracy of pulmonary artery pressure estimated by TR, Groh et al found DE inaccurately estimated right ventricular pressure in children with elevated right heart pressure. Our results provided further evidence that DE tended to overestimate sPAPRHC at low sPAPRHC level and increasingly underestimated the sPAPRHC with the advance of sPAPRHC level. We speculated that the coupling mechanism between RV contractility and its load may account for this phenomenon. sPAPRHC is mildly elevated during the initial phase of PH, RV coupling is maintained by a 4- to 5-fold increase in contractility through muscle hypertrophy as well as changes in muscle properties. The compensatory enhancement of RV contractility would make TR Vmax become higher, sPAPRHC will be overestimated by DE, while the PAP is still in the normal range due to the natural vascular elasticity. As sPAPRHC increased moderately, the compensatory contractility of RV would halt and the stroke volume (SV) would decrease, but CO is maintained by increasing heart rate. At this stage of PH, the estimation of sPAPRHC by DE is relatively reliable. However, sPAPRHC would become higher with the development of PH, when RV uncoupling occurs, CO would reduce which will result in increasing of RV preload. The elevated RV preload and RAP would lead to a decreased right atrial-ventricular pressure gradience, thus DE would underestimate the sPAPRHC. sPAPRHC level may affect the accuracy of sPAPECHO through coupling mechanism between RV contractility and its load, but studies with larger sample sizes are needed test this hypothesis.
As our result indicated that DE tends to overestimate the pressure at low sPAPRHC level. So a diagnostic threshold higher than the empirical formula is more suitable for assigning the likelihood of PH during the initial stage of disease to avoid excessive invasive examination. For patients with high sPAPRHC level, attention should be paid to comprehensively assess RV contractility, TR severity and other signs to avoid underestimation of pressure and wrong evaluation of condition. At last, we didn’t find RV systolic parameters and heart function index (6M WT and WHO functional class) have significant impact on the accuracy of sPAPECHO neither. Theoretically, RV systolic function will gradually decrease , but the RV can remain coupled for the large increase in load by increasing contractility until heart failure. Therefore, RV systolic parameters are relatively stable before the end stage of PH. In addition, the heart movement and measurement angle dependence also affect the accuracy of the relevant parameters. While the evaluation of heart function index is closely related to the coordination of patients and the subjectivity of physician which may bring uncertainties. Although RV systolic parameters and heart function index had clinical significance for the assessment of PH, they didn’t have significant effect on the accuracy of sPAPECHO estimation.