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Year : 2022  |  Volume : 32  |  Issue : 4  |  Page : 212-217

Association between right ventricle–Pulmonary artery coupling with in-hospital outcome after triple valve surgery in rheumatic heart disease

1 Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Indonesia, National Cardiovascular Center Harapan Kita, West Jakarta, Indonesia
2 Department of Cardiovascular and Thoracic Surgery, Faculty of Medicine, Universitas Indonesia, National Cardiovascular Center Harapan Kita, West Jakarta, Indonesia

Date of Submission14-Sep-2022
Date of Acceptance14-Sep-2022
Date of Web Publication23-Jan-2023

Correspondence Address:
Amiliana Mardiani Soesanto
Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Indonesia, National Cardiovascular Centre, Harapan Kita, Jl. Let. Jend. S. Parman Kav. 87, Slipi, Jakarta 11420
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcecho.jcecho_57_22

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Context: Triple valve surgery (TVS) is a relatively higher in-hospital mortality rate than any isolated valve surgery. In advanced-stage valvular heart disease, maladaptation may occur, creating RV-PA uncoupling. Aims To evaluate whether RV-PA coupling is associated with the in-hospital outcome of patients after TVS. Settings and Design: From the medical records, clinical and echocardiography data were collected and compared between the survived and patients with in-hospital mortality groups. Methods and Material: Patients with the rheumatic multivalvular disease who underwent triple valve surgery were included in the study. Statistical and analysis used Uni and bivariate analysis assessed any association between the RV-PA coupling using TAPSE/PASP and other clinical variables with the in-hospital mortality post TVS. Result: From 269 patients, the in-hospital mortality rate was 10 %. The median value of TAPSE/PASP ratio in all group is 0.41 (0.02-5.79). Impaired RV-PA coupling which value < 0.36 occurs in 38.3 % population. By multivariate analysis, independent predictors of in-hospital mortality were TAPSE/PASP < 0.36 (OR 3.46, 95 % CI 1.21 – 9.89; P 0.02), age (OR 1.04, 95 % CI 1.003-1.094; P 0.035), CPB duration, (OR 1.01, 95 % CI 1.003-1.017; P 0.005). Conclusion: RV-PA uncoupling assessed by TAPSE / PASP ratio < 0.36 is associated with the in-hospital mortality in patients post triple valve surgery. Other factors associated with the outcome were older age and longer CPB machine duration.

Keywords: In-hospital mortality, right ventricle–pulmonary artery uncoupling, triple valve surgery

How to cite this article:
Soesanto AM, Hendiperdana MR, Zahara R, Tjubandi A, Juzar D, Iryuza N, Siagian SN. Association between right ventricle–Pulmonary artery coupling with in-hospital outcome after triple valve surgery in rheumatic heart disease. J Cardiovasc Echography 2022;32:212-7

How to cite this URL:
Soesanto AM, Hendiperdana MR, Zahara R, Tjubandi A, Juzar D, Iryuza N, Siagian SN. Association between right ventricle–Pulmonary artery coupling with in-hospital outcome after triple valve surgery in rheumatic heart disease. J Cardiovasc Echography [serial online] 2022 [cited 2023 Apr 1];32:212-7. Available from: https://www.jcecho.org/text.asp?2022/32/4/212/368436

  Introduction Top

Multivalvular disease (MVD) occurs in 20.2% of all valvular heart diseases, with rheumatic heart disease (RHD) as the common etiology.[1],[2] Triple valve surgery (TVS) with several predictors carries a higher surgical risk than isolated valve surgery, including a mortality range from 2.5% to 25%.[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12]

Pulmonary hypertension (PH) as a complication of valvular heart disease may increase right ventricle (RV) afterload. The RV adaptation known as RV–pulmonary artery (PA) coupling is aimed at maintaining the cardiac output. As the disease progresses, the RV-PA uncoupling takes place, and then cardiac output is reduced. Tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) is a surrogate marker for the RV-PA uncoupling, a sign of the RV maladaptive process, which can be detected clinically as signs and symptoms of RHF. The late maladaptive stage of the disease may be used as a novel prognostic factor for in-hospital mortality in patients post-TVS.[13],[14]

This study aimed to determine whether RV-PA coupling presented by TAPSE/PASP ratio can predict the in-hospital outcome of the TVS procedure in rheumatic MVD.

  Subjects and Methods Top

We retrospectively observed patients with rheumatic MVD who underwent the TVS procedure at our center between January 2012 and April 2021. Any concomitant surgery, including coronary artery bypass graft, congenital heart disease repair, or valve surgery history, was excluded from the study. Clinical data, laboratory, and echocardiography were obtained from the medical record. The ethical committee from our center granted the ethical clearance.

For the aim of the study, we followed the patient during hospitalization and divided the group into the survival group and the mortality group. The clinical and echocardiography data were compared between both groups. We then specifically evaluated the association between TAPSE/PASP as a surrogate echocardiography marker of RV-PA coupling with the clinical outcome. The study's outcome was all-cause in-hospital mortality, obtained from the patient's medical record.

For the clinical variables, we included age, sex, preoperative right heart failure (RHF), heart failure (HF), New York Heart Association (NYHA) functional class, atrial fibrillation (AF), serum creatinine, and body surface area. Preoperative RHF is defined by the presence of any systemic venous congestion signs, including hepatomegaly, ascites, and peripheral edema. We obtained patient clinical data retrospectively from hospital electronic medical records before the TVS procedure.

Transthoracic echocardiography was done before surgery. The echocardiographic parameters were left ventricular (LV) ejection fraction, TAPSE, tricuspid regurgitation velocity max (TR Vmax), and LV end-diastolic dimension. An echocardiographic assessment was performed according to the American Society of Echocardiography guidelines.[15],[16],[17] TAPSE/PASP ratio as a surrogate marker of RV-PA uncoupling. A TAPSE/PASP ratio value <0.36 was used as the surrogate marker of RV-PA uncoupling.[18],[19]

Continuous variables were presented as mean ± standard deviation for normal data distribution or median (interquartile range) for abnormal ones. Categorical variables were presented as a percentage. We compared the two groups using the t-test and the Mann–Whitney U-test for parametric and nonparametric continuous. Categorical values were compared using the Chi-square test. Binary logistic regression analysis was used to analyze multivariate data to model the relationship between those variables that were significant in the bivariate analysis. Crude odds ratios (ORs) were obtained after considering the effect of significant variables in the bivariate analysis, and adjusted ORs were obtained after including all variables that showed significance in the crude OR analysis. The 95% confidence interval (CI) was used to estimate the precision of the odds. A P < 0.05 was considered statistically significant. The Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, version 20, IBM Corp. Armonk, N.Y., USA) was used for data analysis.

  Result Top

Two hundred and seventy-nine patients underwent the TVS procedure during the study, but only 269 patients met the inclusion criteria for final analysis. Therefore, 10 patients were excluded from the study, including four patients who had prior valve surgery, four who had concomitant surgery with congenital heart disease repair, and two who had concomitant surgery with coronary artery bypass surgery. The median age was 39 (17–65) years, and 148 (55%) were women. At baseline, 106 (39.4%) patients had Class IV NYHA functional class, 172 (63.9%) patients had AF, preoperative RHF was found in 80 (29.7%) patients, and 10 (3.7%) patients had active endocarditis before surgery.

Clinical and echocardiographic characteristics according to the absence or presence of outcome are provided in [Table 1]. In-hospital mortality was significantly higher in older patients (P = 0.002) and patients with a longer cardiopulmonary bypass (CPB) duration (P = 0.018). AF (P = 0.015) and preoperative RHF (P = 0.027) were also higher in the outcome group. However, echocardiographic variables showed no difference between the two groups except for the TAPSE/PASP ratio variable.
Table 1: Baseline clinical and echocardiographic characteristics according to the absence or presence of in-hospital mortality outcome

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Clinical outcome and predictor of all-cause in-hospital mortality

All patients were followed postoperatively until hospital discharge. In-hospital mortality occurred in 27 (10%) patients. Using bivariate analysis, in-hospital mortality was significantly higher in patients with older age (P = 0.002), longer CPB machine duration (P = 0.018), and lower value of TAPSE/PASP ratio (P = 0.014). Furthermore, the presence of AF (OR 3.58, 95% CI 1.2–10.7; P = 0.015), preoperative RHF (OR 2.42, 95% CI 1.08–5.42; P = 0.027), and TAPSE/PASP ratio < 0.36 (OR 3.69, 95% CI 1.59–8.57; P = 0.001) also associated with higher in-hospital mortality.

In multivariate logistic regression analysis, per unit increase of age (year) increased OR 1.04 (P = 0.035) and per unit increase CPB machine duration (minute) increased OR 1.01 (P = 0.005), and TAPSE/PASP ratio <0.36 remained significant independent predictors associated with in-hospital mortality [Table 2].
Table 2: Bivariate and multivariate logistic regression analysis of variables associated with in-hospital mortality event in rheumatic heart disease patient who underwent triple valve surgery

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Factors associated with right ventricle–pulmonary artery uncoupling

We then evaluated factors associated with RV-PA uncoupling marked by TAPSE/PASP ratio <0.36. [Table 3] shows a difference in characteristics between TAPSE/PASP ratio <0.36 and >0.36 group. There is no significant difference in baseline characteristics between impaired and preserved RV-PA coupling, except for AF and the echocardiographic component of RV-PA coupling (TAPSE and TR Vmax).
Table 3: Baseline clinical and echocardiographic characteristics according to tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio values

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  Discussion Top

We found that in-hospital mortality of this study was 10%, which was lower than the previous similar studies. Their studies reported that in-hospital mortality ranged from 12.6% to 16.1%.[3],[7],[9] Meanwhile, similar studies with a high prevalence of RHD reported lower in-hospital mortality rates. Fadel et al. from Saudi Arabia reported that in-hospital mortality from TVS was 11%, Davarphasand from Iran reported 6%, and Han from China reported 8% in-hospital mortality.[4],[10],[20]

In our study, the median age of our patients was 39 years old. A higher in-hospital mortality rate was found in older patients. In previous similar studies, the median age was between 58–70 years old.[3],[6],[7],[9] Perhaps, it could be explained by different etiologies of the MVD. Our patients were dominated by rheumatic etiology, whereas their studies were dominated by degenerative etiology. Meanwhile, similar studies from the high prevalence of RHD countries reported almost equal median age of patients. The mean ages of their study range from 34 years old[10] to 40 years old.[4],[20]

One of the hemodynamic consequences of MVD is PH, which leads to increased RV afterload.[14] An increase in pulmonary vein resistance contributes to Group 2 PH in MVD, and rises the pulmonary vascular resistance burden to 40%.[21] The RV will adapt to this burden by increasing wall thickness and contractility. The RV adapts to high pulmonary valve replacement (PVR) by increasing 4–5 folds of ventricular contractility and hypertrophy remodeling in the initial phase. This adaptation is aimed at maintaining the cardiac output and is called RV-PA coupling. As the disease progresses, the RV hypertrophic adaptation will discontinue in the later stage, and the wall stress increases. To further maintain the cardiac output, the RV dilates, the heart rate increases until the RV-PA uncoupling takes place, and then cardiac output is reduced.[13],[14],[22] TAPSE/PASP is a surrogate marker for the RV-PA uncoupling, a sign of the RV maladaptive process, which can be detected clinically as signs and symptoms of RHF.[14],[22] This variable might occur in the late adaptive stage of PH due to valvular heart disease. Therefore, it has been reported as a prognostic factor and can be used as a novel prognostic factor for in-hospital mortality in patients post-TVS.

In our study, we found TAPSE/PASP ratio <0.36 in 103 (38.3%) patients. In [Table 1], there was a significant difference in TAPSE/PASP ratio between the mortality and nonmortality groups. Further, we found that TAPSE/PASP <0.36 was an independent predictor for in-hospital mortality (adjusted OR 3.46, 95% CI 1.21–9.89; P = 0.02). It suggested that RV-PA uncoupling is an independent predictor of in-hospital mortality for TVS in addition to other conventional predictors such as older age and prolonged CPB machine duration. So far, no studies have reported an association between TAPSE/PASP with in-hospital mortality of the TVS. Guazzi et al. reported a cutoff value <0.36 associated with lower survival in 293 HF patients in a 20-month follow-up.[19] Ghio et al. also reported that the TAPSE/PASP ratio <0.36 was associated with higher mortality in 1163 patients with HF who followed up for 46 months.[18] Nakagawa et al. reported a higher TAPSE/PASP ratio with cutoff <0.48 as an independent prognostic factor composite endpoint in decompensated HF with preserved ejection fraction (HFpEF) (hazard ratio 1.77 [95% CI, 1.34–2.32], P < 0.0001).[23] Panaioli et al. reported RV-PA uncoupling in the postoperative repair of tetralogy of Fallot (rTOF) with significant pulmonary regurgitation. A lower TAPSE/PASP ratio value becomes a significant predictor of PVR indication.[24]

Further, we evaluated any factors associated with the RV-PA coupling by comparing the TAPSE/PASP ratio groups <0.36 and >0.36. There is no difference in characteristics between the two groups, except for the high prevalence of AF in the TAPSE/PASP <0.36 group (P = 0.015) [Table 3]. It suggests that AF may have a detrimental effect on RV-PA coupling. Several studies also reported the correlation between AF and RV-PA coupling. Omote et al. found that patients with HFpEF associated with AF showed more severe PH and pulmonary vascular disease than those without AF. Hence, the patients with AF had more pronounced RV-PA uncoupling.[25] Nakagawa et al. reported that AF rhythm is more common in the impaired RV-PA uncoupling group (55%; P < 0.0001).[23] In patients with Group 2 PH concomitant with AF, a higher mean PA, profound pulmonary vascular dysfunction, and impairment of RV function were detected compared to the one with sinus rhythm.[26] They suggested that the negative inotropic effect of AF might be a contributing factor to RV-PA uncoupling.[23],[26]

This study shows a significant proportion of preoperative RHF at 29.7%. Symptomatic RHF is a clinical manifestation that rises when RV encounters a high afterload burden due to Group 2 PH. The adaptive mechanism of RV to overcome the afterload is increasing hypertrophy for maintaining RV-PA coupling. RHF is the end spectrum of these RV maladaptive processes toward high PVR and marks the beginning of RV-PA uncoupling.[27],[28] Symptomatic RHF spectrum-like peripheral ascites edema was also reported by Han et al., whereas preoperative RHF was found in 38% of patients. Han et al. also reported that preoperative RHF was associated with early mortality after TVS with OR 10.7 (P < 0.0001).[4] However, after interaction with other variables, we did not find any significant correlation between RHF and the outcome. Perhaps, the RV-PA coupling is more representative of the RV maladaptive response.

Age and CPB duration variables incrementally increased mortality per one variable unit rise (year and minute, respectively). Previous studies reported a similar result of longer CPB time being an independent predictor of early mortality after TVS. Their studies also reported longer overall mean CPB time compared with our study, (164 ± 86 min), (193 ± 7 min), and (201 ± 70 min), respectively.[9],[20],[29]

Since this study is a retrospective study and data collection was from the medical record, it will inherit the nature of secondary data. Selection bias may occur since patients who underwent the TVS procedure were unlikely to have a very high surgical risk, as decided in our surgical conference before surgery. Another limitation is that our study is a single-center study; a further multicenter study is needed to generalize the finding of our study.

  Conclusion Top

Our study found that RV-PA uncoupling assessed by TAPSE/PASP ratio <0.36 is associated with in-hospital mortality in patients post-TVS. Other factors associated with the outcome were older age and longer CPB machine duration.


The authors would like to thank Iwan Dakota, MD, Ph.D. (Director of The National Cardiovascular Center Harapan Kita), Renan Sukmawan, MD, Ph.D. (Head of Cardiology and Vascular Medicine Department, Universitas Indonesia), and Fadhila Nafilah Azzahra (research assistant) for making this study possible.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Table 1], [Table 2], [Table 3]


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