Study population

During the study period, a total of 206 patients met the inclusion criteria and were entered in the analysis. The mean age was 78.5 ± 7.1 years, and 58.3% were female. The study participants were at a high risk for surgery (EuroSCORE II: 9.0 ± 6.5%), and massive/torrential TR was observed in 100 (48.5%) of these patients. The majority of patients presented with atrial fibrillation (94.2%), preserved left ventricular ejection fraction (55.2 ± 10.1%), and a secondary etiology of TR (96.1%). All patients were treated either with transcatheter edge-to-edge repair (n = 185: 89.8%) or transcatheter annuloplasty (n = 21: 10.2%). No periprocedural death was observed. TTVR reduced the severity of TR (p < 0.001), with 78.0% of patients having TR 2+ or less at discharge.

RV–PA coupling parameters

Variables regarding echocardiography and right heart catheterization are listed in Table 1. The median values of TAPSE, ePASP, and TAPSE/ePASP were 17.0 mm (IQR 15.0, 20.0 mm), 45.0 mmHg (IQR 36.3, 53.0 mmHg), and 0.392 mm/mmHg (IQR 0.287, 0.514 mm/mmHg). The median time from baseline echocardiography to invasive right heart catheterization was one day (IQR − 1, 5 days). The invasively-measured PASP (i.e., iPASP) was 42.0 mmHg (IQR 35.0, 52.0 mmHg), and the median of TAPSE/iPASP was 0.408 mm/mmHg (IQR 0.316, 0.526 mm/mmHg).

Table 1 Baseline characteristicsPrediction for outcomes according to RV–PA coupling parameters

With the median follow-up duration of 201 days (IQR 98–424 days), 29 patients had died, and 40 patients had experienced rehospitalization due to heart failure, resulting in 57 cases of the primary outcome. The associations of right heart parameters with the primary outcome are listed in Supplemental Table 1. Compared to TAPSE/ePASP, TAPSE/iPASP showed better predictability for the primary outcome (Fig. 1A): the c-statistics was 0.565 (95% CI 0.488–0.643) for TAPSE/ePASP and increased to 0.695 (95% CI 0.631–0.759) when iPASP was applied to the formula (i.e., TAPSE/iPASP) (p < 0.001). The trend was consistent for RV–PA coupling using RVFAC (Fig. 1B). RVFAC itself was not associated with the primary outcome (Supplemental Table 1). Similarly, RVFAC/ePASP was not predictive for the outcome, while RVFAC/iPASP predicted the primary endpoint. As shown in Fig. 1, integrating the iPASP measurement led to a better prediction for the outcome (c-statistics: 0.495 for RVFAC/ePASP [95% CI 0.411–0.578]; c-statistics for RVFAC/iPASP: 0.643 [95% CI 0.566–0.719]).

Fig. 1

Receiver operating characteristics curves of RV–PA coupling. Shown are the receiver operating characteristics curves for each method of RV–PA coupling for predicting the outcome. Predictability was improved by measuring PA pressure invasively before applying the formulas

In addition, we separately conducted ROC analyses in patients with severe and those with massive/torrential TR. TAPSE/iPASP showed a better discrimination irrespective of the TR severity, whereas the difference in Harrell’s C was numerically higher in patients with more advanced TR (delta c-statistics: 0.102 ± 0.035 in severe TR, p = 0.003; delta c-statistics: 0.179 ± 0.056 in massive/torrential TR, p = 0.001).

Correlation between echocardiographic and invasive PA pressures

There was a significant correlation between ePASP and iPASP in the total cohort (correlation coefficient 0.50, p < 0.001), whereas the correlation was attenuated in patients with massive to torrential TR (severe TR: correlation coefficient 0.588, p < 0.001; massive to torrential TR: correlation coefficient 0.337, p = 0.001; interaction p = 0.01) (Fig. 2). A similar trend was observed in the correlation between TR pressure gradient and iPASP (severe TR: correlation coefficient 0.546, p < 0.001; massive to torrential TR: correlation coefficient 0.331, p = 0.001; interaction p = 0.035).

Fig. 2

Correlation between echocardiographic estimated and invasively measured PASP. There was a significant interaction between TR severity and the accuracy of ePASP. The correlation between ePASP and iPASP was attenuated in patients with massive/torrential TR compared to patients with severe TR

In addition, the echocardiographic RA pressure (median 15 mmHg [IQR 8–15 mmHg]) was modestly correlated with the invasive measurement (median 13 mmHg [IQR 9–18 mmHg]) (correlation coefficient 0.165, p value = 0.023) (Fig. 3). The RA pressure was likely to be underestimated in patients with the echocardiographic measurement of 3 and 8 mmHg. The miscalculation was also observed in patients with the echocardiographic RA pressure of 15 mmHg: a quarter of patients showed less than 10 mmHg of the invasive measurement, whereas another quarter showed more than 20 mmHg of the invasively-measured RA pressure.

Fig. 3

Correlation between echocardiographic and invasively measured RA pressure. The RA pressure assessed by echocardiography was weakly correlated with the invasive measurement (median 13 mmHg [IQR 9–18 mmHg]) (correlation coefficient 0.165, p value = 0.023). The median of the invasively-measured RA pressure was 12 mmHg (IQR 9–19 mmHg) in patients with echocardiographic RA pressure of 3 mmHg, 12 mmHg (IQR 8–16 mmHg) in those with echocardiographic RA pressure of 8 mmHg, and 15 mmHg (IQR 10–20 mmHg) in those with 15 mmHg of echocardiographic RA pressure

Clinical implication of TAPSE/iPASP

We divided the study participants according to TAPSE/iPASP (quartile 1: ≤ 0.316; quartile 2: 0.317–0.407, quartile 3: 0.408–0.526, quartile 4: ≥ 0.527). The baseline characteristics are listed in Table 1. Patients with lower TAPSE/iPASP were more likely to be male, having prior coronary artery bypass graft surgery, higher PA resistance and RA pressure, compared to patients with higher TAPSE/iPASP mm/mmHg. TR reduction to ≤ 2+ at discharge was consistently observed regardless of TAPSE/iPASP (Supplemental Table 2).

The spline curve depicts the linear association of TAPSE/iPASP with the primary endpoint (Fig. 4). TAPSE/iPASP was inversely associated with the primary outcome (per 0.1-point increase: adjusted-HR 0.67, 95% CI 0.56–0.82, p < 0.001) in the multivariable Cox proportional model (Table 2). Other parameters associated with the outcome were sex (male: adjusted-HR 2.26, 95% CI 1.21–4.20, p = 0.01) and eGFR (per 1 ml/min/1.73 m2 increase: adjusted-HR 0.98, 95% CI 0.97–0.99, p = 0.008).

Fig. 4

Smooth spline curve for association of TAPSE/iPASP with primary outcome. The spline curve depicts the linear association of TAPSE/iPASP with the primary endpoint

Table 2 Cox proportional hazard model for primary endpoint

The association of TAPSE/iPASP with the outcome remained significant after adjusting for the TR reduction (Table 2). Also, the observed association was consistent among the predefined subgroups, including NYHA functional class, LV ejection fraction, the severity of TR at baseline, and the reduction in TR at discharge (Supplemental Fig. 1).

Event-free survival curves were estimated and depicted using a Kaplan–Meier method (Fig. 5). According to the TAPSE/iPASP quarters (i.e., ≤ 0.316; 0.317–0.407; 0.408–0.526; ≥ 0.527), the event-free survivals were 43.4%, 48.3%, 77.9%, and 85.4% at one year after TTVR. Similar findings were observed for each outcome. The event-free survival from heart failure rehospitalization were 52.0%, 61.8%, 86.4%, and 87.3%, whereas survival from death were 65.0%, 82.1%, 85.9%, and 90.6% at one-year follow-up after TTVR.

Fig. 5

Survival analysis according to TAPSE/iPASP. According to the TAPSE/iPASP quartile (i.e., 1st quartile: ≤ 0.316; 2nd quartile: 0.317–0.407, 3rd quartile: 0.408–0.526, 4th quartile: ≥ 0.527), the event-free survivals were 43.4%, 48.3%, 77.9%, and 85.4% at one year after TTVR, respectively. Similar findings were observed for each outcome