Prognostic significance of right ventricular-pulmonary artery coupling in patients undergoing tricuspid valve surgery

Introduction

The tricuspid valve, often referred to as the “forgotten valve”, has been gaining increasing attention with the emergence of new treatment strategies. Despite surgical and medical improvements, perioperative morbidity and mortality remain significant (1). Particularly, the accurate preoperative assessment of right ventricular (RV) function and its response to the correction of tricuspid pathology and associated changes in flow and pressure is challenging. Unlike the left ventricle, the RV function is highly load dependent, making conventional indices of RV function, such as tricuspid annular plane systolic excursion (TAPSE), less reliable (2-4).

A promising parameter in this context is right ventricular-pulmonary artery (RV-PA) coupling, which quantifies the efficiency of RV systolic function relative to its afterload. Conceptually, RV-PA coupling reflects the matching of contractile performance to vascular load, and is typically assessed invasively by the ratio of end-systolic to arterial elastance (Ees/Ea) (5). However, noninvasive surrogates—such as the ratio of TAPSE to pulmonary artery systolic pressure (PASP)—have shown clinical utility and strong prognostic value in various cardiac populations, including those with pulmonary hypertension, valvular disease, heart failure, and transcatheter valve interventions (5-10). Physiological values of echocardiographically-assessed RV-PA coupling have been described in the range of 0.5–0.7 mm/mmHg (11).

Despite its theoretical and practical appeal, the role of RV-PA coupling in the context of tricuspid valve surgery remains poorly defined. This gap is particularly relevant as RV dysfunction and uncoupling have been shown to predict morbidity and mortality independently (10,12). The prognostic value of RV-PA coupling in patients undergoing tricuspid valve surgery has not been evaluated.

In this study, we aimed to investigate the prognostic utility of RV-PA coupling in patients undergoing tricuspid valve surgery. We hypothesize that impaired RV-PA coupling is associated with worse clinical outcomes and may serve as a more sensitive predictor of RV function than conventional echocardiographic markers.

Methods

Ethical approval

This study was approved by the local ethics committee. Being a retrospective study, informed consent from individual patients was waived (IRB: 2022P001627; approved: 9/13/2022).

Study design and definitions

The institutional database, which includes all patients undergoing cardiac surgery, was queried for patients who underwent either isolated tricuspid valve surgery or combined with left-sided valve surgery from January 2013 to June 2024. Most patients had undergone combined surgery for left-sided and right-sided valvular pathology. Given the retrospective observational design of the study, no sample size calculations were performed. For our analysis, all patients age 18 years or older, with adequate baseline transthoracic echocardiographic images for RV strain function measurements and valve assessment, were included in this study. Patients who underwent surgery for congenital pathologies were excluded from the study. Right ventricular free wall strain (RVFWS) analysis was performed using 2D speckle-tracking imaging software (TomTec, Chicago, IL, USA). All measurements were retrospectively performed using a semiautomated tracing of endocardial borders in the apical four-chamber view and border tracings were visually assessed and adjusted for adequate tracing. Tricuspid regurgitation severity was graded with a combination of semiquantitative (measuring the vena contracta) and qualitative (by assessing color flow Doppler signal) parameters in preoperative echocardiograms (13). For our primary analysis, RV-PA coupling (unit: mm/mmHg) was characterized by the ratio of TAPSE and echocardiographically estimated PA systolic pressure. TAPSE was measured using the M-mode tracings obtained in the apical 4-chamber position. The PASP was measured using the peak TR gradient calculated from the transvalvular velocity and an assumed right atrial pressure of 5 mmHg was added to the calculated value (11). The right atrial pressure was assumed to be 5 mmHg in all patients to ensure consistency of PASP calculation, due to the unreliable estimation of right atrial pressures. In addition, we calculated RV-PA coupling by dividing RVFWS by the peak gradient TR gradients to compare strain-based RV-PA coupling (unit: %/mmHg) as a postoperative predictor in an observational analysis.

Study outcomes

The primary study outcome was mid-term survival. Secondary study outcomes were in-hospital mortality, intensive care unit (ICU) stay, hospital length of stay (LOS), and prolonged inotropic support (longer than 24 hours postoperatively).

Statistical analysis

Categorical variables were expressed as frequencies and percentages and compared using the chi-squared or Fisher’s exact test. Continuous normally distributed variables were expressed as mean and standard deviation, and non-normally distributed variables as median and interquartile range (IQR) and were compared by Student’s t-test or Mann-Whitney U test. For all analyses, P values <0.05 were considered statistically significant.

A maximally selected rank statistics analysis was performed to detect the optimal cut-off value for RV-PA coupling for mortality risk stratification. The study cohort was divided into two groups based on this optimal value. Survival analysis was performed using the Kaplan-Meier method and differences were analyzed using the log-rank test. A Cox proportional hazards analysis including TAPSE, RVFWS and RV-PA ratio adjusted for left ventricular ejection fraction (LVEF), atrial fibrillation, diabetes and glomerular filtration rate (GFR) was performed, analyzing the relationship between RV function parameters and mortality. To compare the prognostic accuracy of RV-PA coupling indices as predictors of mortality [RVFWS/systolic pulmonary artery pressure (sPAP) vs. TAPSE/sPAP], we used time-dependent receiver operating characteristic (ROC) analysis at 12 months. The area under the curve (AUC) was estimated using the timeROC package in R. To assess the difference in AUCs between the two predictors, we performed nonparametric bootstrap resampling with 1,000 iterations. In each iteration, paired AUCs were calculated on bootstrap samples, and the distribution of AUC differences was used to estimate the 95% confidence interval and P value. Additionally, we analyzed time-dependent AUC values to compare the discriminative performance at varying time points. All analyses were performed using R statistical Software (v.4.4.1; R Core Team 2025; packages: ggplot2, maxstat, rms, survival, tableone).

Results

Patient characteristics

A total of 264 patients were included in our analysis, with a mean age of 67.4±13.5 years, and 64.5% (n=144) were female. The baseline patient characteristics are shown in Table 1. The majority of patients had preoperative atrial fibrillation (86.4%, n=228) and the mean STS risk score was 4.97%.

The patient cohort was stratified into two groups based on our calculated optimal RV-PA cut-off value of 0.339 mm/mmHg. The distribution of RV-PA ratios is illustrated in Figure 1, with a median ratio of 0.25 mm/mmHg (IQR, 0.20–0.29 mm/mmHg) in the lower group and a median ratio of 0.48 mm/mmHg (IQR, 0.40–0.56 mm/mmHg) in the higher coupling group. The rate of diabetes (36.2%, n=34 vs. 15.3%, n=26, P<0.001) was higher in the lower RV-PA group, and GFR (55.6±25.6 vs. 67.0±23.5 mL/min, P<0.001) was lower. Other baseline characteristics were comparable between the two groups.

Figure 1 Boxplot of the distribution of RV-PA coupling, measured by the TAPSE/PASP ratio, stratified by a calculated optimal cutoff value of 0.339 mm/mmHg. Two groups were defined: “Lower” (blue) and “Higher” (yellow) TAPSE/PASP based on this threshold. ****, P<0.0001. PASP, pulmonary artery systolic pressure; RV-PA, right ventricular-pulmonary artery; TAPSE, tricuspid annular plane systolic excursion.

Echocardiographic measurements and perioperative details

Preoperative echocardiographic measurements are shown in Table 2. The mean LVEF was 61.3% with no difference between the groups. RV function parameters were impaired in the lower RV-PA group in comparison to the higher RV-PA group (TAPSE: 15.3±3.6 vs. 20.7±4.3 mm, P<0.001; RVFWS: −19.1%±9% vs. −21.5%±5.7%, P<0.001). The PASP was significantly higher in the lower RV-PA group (64.2±14.9 vs. 43.2±10.3 mmHg). Overall, 93.9% (n=248) of patients had at least moderate TR, with a slightly higher number in the lower RV-PA group. However, there was no difference in mean vena contracta between both groups (8.0±2.2 vs. 7.7±2.8 mm, P=0.37). The perioperative details are summarized in Table 3. The majority of patients underwent tricuspid valve repair (95.5%, n=252) with no difference between the two groups. There was a higher rate of mitral valve repair in the higher RV-PA group compared to the lower RV-PA group (41.8% vs. 23.4%, P=0.004).

Survival analysis and in-hospital outcomes

The overall all-cause mortality was higher in the lower RV-PA group compared to the higher RV-PA group (25.5% vs. 10.0%; P<0.002). The median follow-up was 23 months (IQR, 7–48 months). The Kaplan-Meier analysis showed significantly lower survival rates in patients with lower RV-PA coupling compared to those with higher RV-PA coupling (72.5% vs. 83.3%, log-rank P=0.0038) (Figure 2). In-hospital mortality (10.6%, n=10 vs. 2.9%, n=5, P<0.001), ICU stay [4 (IQR, 3–8) vs. 3 (IQR, 1.25–5) days, P<0.001], hospital stay (11.5 (IQR, 8–17) vs. 9 (IQR, 7–13) days, P<0.001) and postoperative prolonged need for pressors (45.7%, n=43 vs. 21.8%, n=37, P<0.001) was higher in the lower RV-PA coupling group.

Figure 2 Kaplan-Meier survival curves for all-cause mortality stratified by RV-PA coupling defined as TAPSE/PASP ratio. CI, confidence interval; PA, pulmonary artery; PASP, pulmonary artery systolic pressure; RV, right ventricular; sPAP, systolic pulmonary artery pressure; TAPSE, tricuspid annular plane systolic excursion.

We constructed multiple multivariable Cox regression models using different echocardiography-based RV function parameters to assess the association with mortality. All models were adjusted for LVEF, preoperative atrial fibrillation, diabetes and GFR. The covariates were selected based on prior clinical knowledge.

Higher TAPSE-based RV-PA coupling [hazard ratio (HR): 0.09, 95% confidence interval (CI): 0.008–0.95, P=0.04] and RV-strain-based RV-PA coupling (HR: 0.08, 95% CI: 0.015–0.47, P=0.005) showed decreased risk of mortality. In contrast, the isolated RV function parameters TAPSE (HR: 0.96, 95% CI: 0.96–1.04, P=0.31) and RVFWS (HR: 0.96, 95% CI: 0.96–1.12, P=0.34) showed no association with mortality. In all models, higher GFR was significantly associated with decreased mortality (HR: 0.98, 95% CI: 0.96–0.99, P<0.05).

To compare the TAPSE-based and RV strain-based models, we performed a time-dependent ROC analysis. The optimal cut-off value for RVFWS/TAPSE was −0.490%/mmHg. The time-dependent AUC at 12 months was 0.695 for the strain-based RV-PA and 0.690 for the TAPSE-based RV-PA, indicating comparable discriminatory performance between both parameters (Figure 3). The difference in AUC between the two parameters was small and statistically insignificant, verified by bootstrap resampling (mean DAUC =0.004, 95% CI: −0.11 to 0.12, P=0.97). The discriminatory performance of both parameters remained stable for up to 36 months of survival and then decreased (Figure 4).

Figure 3 Time dependent AUC for 12-month survival comparing strain based and TAPSE based RV-PA coupling. AUC, area under the curve; PA, pulmonary artery; RV, right ventricular; sPAP, systolic pulmonary artery pressure; TAPSE, tricuspid annular plane systolic excursion.

Figure 4 Time dependent AUC for strain and TAPSE based RV-PA coupling. AUC, area under the curve; PA, pulmonary artery; RV, right ventricular; sPAP, systolic pulmonary artery pressure; TAPSE, tricuspid annular plane systolic excursion.

Discussion

This study demonstrates that impaired preoperative RV-PA coupling, assessed by the ratio of TAPSE and PASP, is an independent predictor of postoperative morbidity and mid-term mortality in patients undergoing isolated or combined tricuspid valve surgery. Patients with lower RV-PA coupling ratios had significantly lower 5-year survival, higher in-hospital mortality, required prolonged inotropic support, and had longer intensive care and hospital stays. These findings underscore the importance of RV-PA coupling as a non-invasive, easily accessible metric that offers superior prognostic value to isolated RV function parameters. In a sub-analysis, the RVFWS-based RV-PA coupling assessment showed comparable discriminatory value for risk prediction in our study cohort. However, TAPSE/PASP and RVFWS/PASP represent distinct surrogates of RV-PA coupling derived from different physiological assumptions and are not interchangeable.

RV-PA coupling serves as a surrogate for the interplay between RV contractility and pulmonary arterial afterload. In contrast to conventional RV functional parameters, such as TAPSE, RV fractional change, or RV-PA coupling, it integrates the measurement of RV functional reserve against its afterload. Higher RV-PA coupling ratios indicate a higher afterload reserve and preserved RV contractility. In the setting of tricuspid regurgitation, the RV is exposed to chronic volume overload, often with preserved TAPSE and RV dimensions (14). The correction of the tricuspid pathology leads to a decrease in volume overload and can improve RV performance (15,16). However, predicting the ability of the RV to recover after tricuspid valve surgery is challenging and RV-PA coupling could be a valuable clinical parameter for the assessment of RV recovery.

The association between RV-PA uncoupling and adverse outcomes has previously been established in various patient populations. Tello et al. showed in patients with pulmonary hypertension that patients with a TAPSE/PASP <0.31 mm/mmHg had a significantly worse prognosis compared to a higher TAPSE/PASP ratio (5). In the field of transcatheter valve therapies, studies by Brener et al. have shown an association between RV-PA ratios and mortality in patients undergoing mitral valve transcatheter therapy for secondary mitral regurgitation and patients undergoing tricuspid transcatheter therapy in the TriValve registry, with an optimal cut-off value in the TriValve registry of 0.406 mm/mmHg (8,9). Chehab et al. analyzed the predictive value of the TAPSE/PASP ratio in patients undergoing mitral valve surgery and identified that a ratio ≤0.35 is an independent predictor of all-cause mortality and prolonged hospital stay (17).

In an analysis of patients with secondary tricuspid regurgitation, Fortuni et al. (10) showed that a lower TAPSE/PASP ratio is associated with a higher hazard of all-cause mortality. In their cohort, a TAPSE/PASP ratio of 0.31 mm/mmHg was a suitable threshold for risk stratification. Our study verifies the previously published findings of the association between TAPSE/PASP ratios and all-cause mortality and expands the findings to the field of tricuspid valve surgery. Our optimal cut-off value of 0.339 aligns with other published thresholds. However, a generally applicable cut-off value for all patients has not yet been established and varies between 0.3 and 0.4 mm/mmHg (11).

The association of RV dysfunction with adverse outcomes in TV surgery has previously been established and was consequently implemented in risk assessment, as in the TRI-SCORE (18-20). The RV dysfunction assessment in these studies is performed using either TAPSE, doppler tissue imaging peak systolic annular velocity (S'), or by visual assessment. Our findings suggest that RV-PA coupling is a more sensitive and specific prognostic marker in this patient population and should be considered as an additional parameter in preoperative risk assessment. The routine clinical implementation could direct patients to therapy earlier before RV dysfunction develops, or identify patients who require more aggressive treatment of RV dysfunction, or could benefit from staged interventions or transcatheter therapies. Ultimately, it could add accuracy in patient risk prognostication and help inform patients. Future studies are required to analyze the added value of RV-PA coupling to existing risk scores.

Limitations

The present study, being retrospective, is susceptible to all the inherent weaknesses of such analyses. Unmeasured differences between the two groups could introduce bias and influence our results. In 56 patients, insufficient images for echocardiographic analysis were available and had to be excluded. The echocardiography-based measurement of PASP approximates the exact values and becomes challenging in higher degrees of TR. Due to the missing invasive PASP values, we were unable to cross-validate our echocardiographic findings. The right atrial pressure was assumed to be 5 mmHg in all patients which may underestimate true PASP. This limitation may affect absolute PASP and RV-PA coupling values. The majority of patients had left-sided valvular pathology in addition to tricuspid regurgitation, which leads to a limited generalizability in the setting of isolated surgical TVR. Although our findings align with previously published results in other cohorts, the generalizability of our results may be limited due to the single-center study setting at an academic institution. External validation in a separate cohort should be performed to verify our findings.

Conclusions

Echocardiography-derived RV-PA coupling is a robust, independent predictor of adverse outcomes in patients undergoing tricuspid valve surgery, particularly in those undergoing combined procedures. It captures a critical dimension of RV physiology not fully appreciated by standard measures and may serve as a powerful tool in surgical risk stratification and patient selection.

Acknowledgments

None.

Footnote

Funding: None.

Conflicts of Interest: The authors have no conflicts of interest to declare.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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