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Abstract

 
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OBJECTIVES

The clinical significance of persistent end-diastolic forward flow (EDFF) after pulmonary valve replacement (PVR) remains unclear in patients with repaired tetralogy of Fallot. This study aimed to identify the characteristics of these patients and the impact of persistent EDFF on outcomes.

METHODS

Of 46 consecutive patients who underwent PVR for moderate to severe pulmonary regurgitation between 2003 and 2019, 23 (50%) did not show EDFF before PVR [group (−)]. In the remaining 23 patients with EDFF before PVR, EDFF was diminished after PVR in 13 (28%) [group (+, −)] and persisted in 10 (22%) [group (+, +)]. The following variables were compared between these 3 groups: (i) preoperative right ventricular (RV) and right atrial volumes measured by magnetic resonance imaging, haemodynamic parameters measured by cardiac catheterization and the degree of RV myocardial fibrosis measured by RV biopsy obtained at PVR and (ii) the post-PVR course, development of atrial arrhythmia and need for intervention.

RESULTS

A high RV end-diastolic pressure, a greater right atrial volume index and a greater RV end-systolic volume index before PVR and a high degree of RV fibrosis were significantly associated with persistent EDFF 1 year after PVR. Persistent EDFF was a significant risk factor for postoperative atrial tachyarrhythmia, and catheter ablation and pacemaker implantation were required more frequently in these patients.

CONCLUSIONS

Persistent EDFF after PVR could predict a worse prognosis, especially an increased risk of arrhythmia. Close follow-up is required in patients with persistent EDFF for early detection of arrhythmia and prompt reintervention if necessary.

Clinical trial registration number

Institutional review board of Osaka University Hospital, number 16105

Pulmonary end-diastolic forward flow, Tetralogy of Fallot, Pulmonary valve replacement, Atrial tachyarrhythmia, Restrictive right ventricle

INTRODUCTION

Progressive damage to the myocardium of right ventricle (RV) from chronic volume load results in remodelling of the RV in patients with chronic pulmonary valve insufficiency (PI) late after repair of tetralogy of Fallot (TOF) [1, 2]. Pulmonary valve replacement (PVR) has been reported to be effective for reduction of RV volume, improvement of RV function and decreasing the risk of adverse events, including arrhythmia and death [3–5]. Although knowledge about how to improve the long-term outcomes of PVR is gradually accumulating, further investigations of diastolic dysfunction before and after PVR are required in patients with repaired TOF [5–7].

End-diastolic forward flow (EDFF) in the main pulmonary artery reportedly occurs in 31–80% of patients with repaired TOF and has long been regarded as a manifestation of restrictive RV physiology, which is a phenomenon of diastolic dysfunction in a poorly compliant RV [8–15].

However, recent studies have shown that EDFF is a more complex phenomenon associated with not only decreased RV compliance but also the grade of pulmonary regurgitation, the size of the RV and the contractile efficiency of the atrium [14–16]. Furthermore, a prospective study showed that the EDFF was diminished in 85% of patients after PVR [13]. These studies suggest that patients with persistent EDFF after insertion of a pulmonary valve have the restrictive nature of the RV itself, that is, adverse RV remodelling. Few studies have included long-term follow-up of patients with EDFF after PVR, and persistent EDFF has never been investigated in these patients. Examination of the characteristics of patients with persistent EDFF may elucidate the features of restrictive RV physiology resulting from adverse RV remodelling. Furthermore, the clinical significance of persistent EDFF and its impact on the long-term prognosis after PVR remains unclear. The aim of the present study was to identify (i) the characteristics of patients with repaired TOF who have persistent EDFF after PVR and (ii) the impact of persistent EDFF after PVR on their clinical outcomes.

MATERIALS AND METHODS

Patients

This retrospective study was approved by our Institutional Review Board (approval number 16105) and written informed consent for use of patient records was obtained from the legal guardian of each patient. Between January 2003 and December 2019, 51 patients underwent PVR for moderate to severe pulmonary regurgitation and examination for EDFF both before and after PVR at our institution. Five patients were excluded because of chronic atrial fibrillation before PVR due to inadequate evaluation of EDFF. Finally, 46 consecutive patients were included in the study (22 male; median age at PVR, 36.5 years; Table 1). The cohort was divided into 3 groups according to the presence of EDFF before or after PVR: group (−), which showed no EDFF before PVR; group (+, −), which showed EDFF before PVR that diminished after PVR; and group (+, +), which showed persistent EDFF before and after PVR (Fig. 1). The haemodynamic data, RV and right atrial (RA) volumes and histological findings in the RV myocardium obtained at PVR were compared between the 3 groups.

Patients selection process. Patients were divided into 3 groups according to the presence of pulmonary end-diastolic forward flow before and after pulmonary valve replacement. EDFF: pulmonary end-diastolic forward flow; PVR: pulmonary valve replacement.
Figure 1:

Patients selection process. Patients were divided into 3 groups according to the presence of pulmonary end-diastolic forward flow before and after pulmonary valve replacement. EDFF: pulmonary end-diastolic forward flow; PVR: pulmonary valve replacement.

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Table 1:
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Study population: demographics and surgical characteristics

Patientsn = 46
Male sex22 (48%)
Age at PVR (years)37 [26–45]
End-diastolic forward flow before PVR23 (50%)
Atrial tachyarrhythmia before PVR16 (35%)
 Paroxysmal atrial fibrillation12 (26%)
 Atrial tachycardia2 (4%)
 Atrial flutter2 (4%)
Catheter ablation before PVR5 (11%)
Previous shunt palliation10 (22%)
Age at primary repair (years)3 [2–5.4]
Type of primary RVOT repair
 Transannular patch17 (37%)
 Commissurotomy + RV patch17 (37%)
 Commissurotomy12 (26%)
Follow-up from correction (years)31 (10)
Patientsn = 46
Male sex22 (48%)
Age at PVR (years)37 [26–45]
End-diastolic forward flow before PVR23 (50%)
Atrial tachyarrhythmia before PVR16 (35%)
 Paroxysmal atrial fibrillation12 (26%)
 Atrial tachycardia2 (4%)
 Atrial flutter2 (4%)
Catheter ablation before PVR5 (11%)
Previous shunt palliation10 (22%)
Age at primary repair (years)3 [2–5.4]
Type of primary RVOT repair
 Transannular patch17 (37%)
 Commissurotomy + RV patch17 (37%)
 Commissurotomy12 (26%)
Follow-up from correction (years)31 (10)

Continuous data are presented as mean (standard deviation) or median [interquartile range], while categorical data are shown as the number (percentage) of observations.

PVR: pulmonary valve replacement; RV: right ventricular; RVOT: right ventricular outflow tract.

Table 1:
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Study population: demographics and surgical characteristics

Patientsn = 46
Male sex22 (48%)
Age at PVR (years)37 [26–45]
End-diastolic forward flow before PVR23 (50%)
Atrial tachyarrhythmia before PVR16 (35%)
 Paroxysmal atrial fibrillation12 (26%)
 Atrial tachycardia2 (4%)
 Atrial flutter2 (4%)
Catheter ablation before PVR5 (11%)
Previous shunt palliation10 (22%)
Age at primary repair (years)3 [2–5.4]
Type of primary RVOT repair
 Transannular patch17 (37%)
 Commissurotomy + RV patch17 (37%)
 Commissurotomy12 (26%)
Follow-up from correction (years)31 (10)
Patientsn = 46
Male sex22 (48%)
Age at PVR (years)37 [26–45]
End-diastolic forward flow before PVR23 (50%)
Atrial tachyarrhythmia before PVR16 (35%)
 Paroxysmal atrial fibrillation12 (26%)
 Atrial tachycardia2 (4%)
 Atrial flutter2 (4%)
Catheter ablation before PVR5 (11%)
Previous shunt palliation10 (22%)
Age at primary repair (years)3 [2–5.4]
Type of primary RVOT repair
 Transannular patch17 (37%)
 Commissurotomy + RV patch17 (37%)
 Commissurotomy12 (26%)
Follow-up from correction (years)31 (10)

Continuous data are presented as mean (standard deviation) or median [interquartile range], while categorical data are shown as the number (percentage) of observations.

PVR: pulmonary valve replacement; RV: right ventricular; RVOT: right ventricular outflow tract.

Definition of end-diastolic forward flow and evaluation

EDFF was defined as antegrade flow of >30 cm/s in the main pulmonary artery with atrial contraction, interrogated by pulsed-wave Doppler and considered present during at least 3 consecutive beats according to the definition proposed by Gatzoulis et al. (Fig. 2) [8]. EDFF was examined by echocardiography before PVR and at a median of 1 year after PVR.

Representative example of pulmonary end-diastolic forward flow detected by Doppler echocardiography. Arrows point to pulmonary end-diastolic forward flow. EDFF: pulmonary end-diastolic forward flow.
Figure 2:

Representative example of pulmonary end-diastolic forward flow detected by Doppler echocardiography. Arrows point to pulmonary end-diastolic forward flow. EDFF: pulmonary end-diastolic forward flow.

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Surgical procedure

The indication for PVR during the study period was the presence of symptoms or signs of RV failure, including palpitation, pedal oedema and atrial arrhythmia. For asymptomatic patients, we scheduled PVR when the RV end-diastolic volume index approached 150 ml/m2 and the RV end-systolic volume index (RVESVI) approached 80 ml/m2 as assessed by cardiac magnetic resonance imaging (MRI) or cardiac computed tomography (CT).

PVR was performed through a median sternotomy using cardiopulmonary bypass with mild hypothermia. Cardiac arrest was performed in 26 patients. A longitudinal incision was made in the pulmonary trunk or in a previously placed patch. Reduction plasty of the infundibulum and complete removal of a previously placed patch was performed if necessary as previously described [17, 18]. PVR was performed using a bioprosthetic valve in 41 patients and a decellularized homograft in 5 patients.

In 14 patients with atrial arrhythmia, the Maze procedure was concomitantly performed at the time of PVR, as per the recent recommendations on management of arrhythmias in adult congenital heart disease [19]. The ablation lines were as previously described [7]. A bipolar radiofrequency system (AtriCure Inc., Mason, OH, USA) and a Frigitronics cryoablation device (CooperSurgical, Trumbull, CT, USA) were used for ablation. Tricuspid annuloplasty and valvuloplasty were performed concomitantly in 29 patients with greater than moderate tricuspid regurgitation or a dysplastic valve cusp. A pacemaker was implanted for sinus node dysfunction at the same time in 4 patients.

Haemodynamic and volume study

Cardiac catheterization was performed before PVR. Echocardiography, cardiac MRI and enhanced CT were performed before PVR, 1 year after PVR, and as part of serial follow-up in all patients.

The RV end-diastolic and end-systolic volumes were evaluated by cardiac MRI in 38 patients. In 8 patients with contraindications for cardiac MRI, the RV volume was evaluated by CT. The methods used for assessment of RV volume have been described previously [18]. All images were analysed by the same expert observer (S. Hamada) who was not otherwise involved in this study and was blinded to the patient characteristics. In 46 patients, the postoperative RV volume was evaluated at a median of 1.1 years after PVR.

The RA volume was evaluated by enhanced CT and MRI [7]. Multidetector cardiac CT examinations were performed using a 64-slice CT system (Discovery CT750 HD; GE Healthcare, Milwaukee, WI, USA). After the reformatted images were transferred to a workstation, contiguous multiphase short-axis images were generated using semi-automated interactive software (Advantage Workstation 4.6, CardIQ Xpress function; GE Healthcare, Buckinghamshire, UK). The RA volume was calculated at the end-diastolic phase, which was identified at 40% of the R–R interval. In each slice, the RA endocardial borders were detected by visual inspection using a combination of volume rendering and multiplanar two-dimensional images. In 7 patients with contraindications to enhanced CT imaging, the RA volume was measured by MRI and calculated using the method devised by Maceira et al. [20].

Histological analysis

The RV myocardial biopsy was obtained from the RV free wall at the time of PVR in 33 patients. The samples were embedded in paraffin, cut into 5-μm-thick sections and stained with Masson’s trichrome stain. The percentage of myocardium that was fibrosed was assessed using MetaMorph 6.2 imaging software (Universal Imaging Corp, Downingtown, PA, USA). Five fields of the mid-layers of the RV wall per slide were analysed, and the average of these fibrotic areas was calculated.

Study design

First, the preoperative characteristics and haemodynamic parameters were compared between the 3 study groups. Pre-PVR atrial arrhythmia included paroxysmal atrial fibrillation, atrial tachycardia and atrial flutter. Patients identified to have chronic atrial fibrillation before surgery were excluded due to inadequate evaluation of EDFF. Second, the post-PVR course, including the status of atrial arrhythmia, was compared between the 3 groups to evaluate the characteristics of patients with persistent EDFF. Atrial arrhythmia after PVR included cases requiring hospitalization or medication. Third, the risk factors for relapse or development of atrial tachyarrhythmia de novo after PVR were analysed.

Statistical analysis

The data are presented as the mean and standard deviation or as the median and interquartile range. Categorical variables were examined using the Cochran–Armitage trend test. Differences between the 3 groups were assessed by one-factor analysis of variance with a post hoc comparison using the Tukey–Kramer method for data that were normally distributed or the Kruskal–Wallis test with a post hoc comparison using the Steel–Dwass test for data that had a skewed distribution.

The incidence of atrial tachyarrhythmia was estimated using Kaplan–Meier curves and compared across groups using the log-rank test. Cox regression hazard models were used to adjust for the effects of preoperative variables on the incidence of atrial tachyarrhythmia post-PVR. In multivariate analysis, persistent EDFF and preoperative right ventricular end-diastolic pressure (RVEDP) were considered for Cox hazard modelling to identify the risk factors for incidence of atrial tachyarrhythmia.

The statistical analysis was performed using JMP Pro version 14 (SAS Institute Inc., Cary, NC, USA). Statistical significance was set at a probability value of P < 0.05.

RESULTS

Baseline and intraoperative characteristics

Follow-up was completed in all patients, with a median follow-up period of 6.0 years (interquartile range 3.8–9.5) after PVR. Group (−) included 23 patients (50%), group (+, −) included 13 patients (28%) and group (+, +) included 10 patients (22%). Group comparisons of baseline and intraoperative characteristics are displayed in Table 2. There was no significant difference between the 3 study groups in terms of the age at initial repair and PVR, the population of patients who underwent modified Blalock–Taussig shunt placement and RV outflow reconstruction with a transannular patch, or history of atrial tachyarrhythmia pre-PVR, including paroxysmal atrial fibrillation, atrial tachycardia or atrial flutter. There was also no significant difference in the proportions of patients who underwent tricuspid valve surgery or a Maze procedure.

Table 2:
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Patient baseline characteristics and intraoperative characteristics

Group (−) [n = 23]Group (+, −) [n = 13]Group (+, +) [n = 10]P-value
Baseline characteristics
 Male to female ratio13:107:62:80.15
 Age at PVR (years)35 (10)37 (13)40 (16)0.51
 Age at initial repair (years)2.5 [2–5]3 [2–5.4]3.1 [2.1–10]0.75
 Interval from initial repair to PVR (years)30 (8)33 (11)33 (11)0.6
 Previous shunt palpitation (n)5 (22%)4 (31%)1 (10%)0.67
 Type of RVOT repair at ICR
  Transannular patch (n)9 (39%)5 (38%)3 (30%)0.45
  Commissurotomy + RV patch (n)6 (26%)5 (38%)6 (60%)
  Commissurotomy (n)8 (35%)3 (23%)1 (10%)
  Catheter ablation before PVR (n)1 (4%)1 (8%)3 (30%)0.073
  Atrial tachyarrhythmia (PAT, PAF, AFL) (n)8 (35%)3 (23%)5 (50%)0.7
  Sick sinus syndrome (n)2 (9%)1 (8%)1 (10%)1.0
Intraoperative characteristics
 ECC time at PVR (min)164 (53)146 (43)160 (55)0.61
 Ao XCl at PVR (n)15 (65%)5 (38%)5 (50%)0.36
 Ao XCl time at PVR (min)86 (36)90 (38)97 (32)0.82
 Type of valve

Bovine: 19 (83%)

Porcine: 2 (8.7%)

DC: 2 (8.7%)

Bovine: 6 (46%)

Porcine: 4 (31%)

DC: 3 (23%)

Bovine: 7 (70%)

Porcine 3 (30%)

0.10
 Valve size (mm)23 [23–25]23 [23–25.5]22 [21–23]0.074
 Concomitant procedure
 TV surgery (n)16 (70%)6 (46%)7 (70%)0.37
 Maze procedure (n)8 (34%)2 (15%)4 (40%)0.46
 Pacemaker implantation (n)2 (9%)1 (8%)1 (10%)1
Group (−) [n = 23]Group (+, −) [n = 13]Group (+, +) [n = 10]P-value
Baseline characteristics
 Male to female ratio13:107:62:80.15
 Age at PVR (years)35 (10)37 (13)40 (16)0.51
 Age at initial repair (years)2.5 [2–5]3 [2–5.4]3.1 [2.1–10]0.75
 Interval from initial repair to PVR (years)30 (8)33 (11)33 (11)0.6
 Previous shunt palpitation (n)5 (22%)4 (31%)1 (10%)0.67
 Type of RVOT repair at ICR
  Transannular patch (n)9 (39%)5 (38%)3 (30%)0.45
  Commissurotomy + RV patch (n)6 (26%)5 (38%)6 (60%)
  Commissurotomy (n)8 (35%)3 (23%)1 (10%)
  Catheter ablation before PVR (n)1 (4%)1 (8%)3 (30%)0.073
  Atrial tachyarrhythmia (PAT, PAF, AFL) (n)8 (35%)3 (23%)5 (50%)0.7
  Sick sinus syndrome (n)2 (9%)1 (8%)1 (10%)1.0
Intraoperative characteristics
 ECC time at PVR (min)164 (53)146 (43)160 (55)0.61
 Ao XCl at PVR (n)15 (65%)5 (38%)5 (50%)0.36
 Ao XCl time at PVR (min)86 (36)90 (38)97 (32)0.82
 Type of valve

Bovine: 19 (83%)

Porcine: 2 (8.7%)

DC: 2 (8.7%)

Bovine: 6 (46%)

Porcine: 4 (31%)

DC: 3 (23%)

Bovine: 7 (70%)

Porcine 3 (30%)

0.10
 Valve size (mm)23 [23–25]23 [23–25.5]22 [21–23]0.074
 Concomitant procedure
 TV surgery (n)16 (70%)6 (46%)7 (70%)0.37
 Maze procedure (n)8 (34%)2 (15%)4 (40%)0.46
 Pacemaker implantation (n)2 (9%)1 (8%)1 (10%)1

Continuous data are presented as mean (standard deviation) or median [interquartile range], while categorical data are shown as the number (percentage) of observations. The statistical analysis was performed using one-way analysis of variance followed by the Tukey–Kramer or the Kruskal–Wallis test with a post hoc comparison using the Dwass post hoc test for multiple comparisons, or the Cochran–Armitage trend test.

AFL: atrial flutter; Ao XCl: aortic cross-clamping; Bovine: bovine pericardial valve; DC: decellularized homograft; ECC: extracorporeal circulation; ICR: intracardiac repair; PAF: paroxysmal atrial fibrillation; PAT: paroxysmal atrial tachycardia; Porcine: porcine valve; PVR: pulmonary valve replacement; RV: right ventricle; RVOT: right ventricular outflow tract; TV: tricuspid valve.

Table 2:
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Patient baseline characteristics and intraoperative characteristics

Group (−) [n = 23]Group (+, −) [n = 13]Group (+, +) [n = 10]P-value
Baseline characteristics
 Male to female ratio13:107:62:80.15
 Age at PVR (years)35 (10)37 (13)40 (16)0.51
 Age at initial repair (years)2.5 [2–5]3 [2–5.4]3.1 [2.1–10]0.75
 Interval from initial repair to PVR (years)30 (8)33 (11)33 (11)0.6
 Previous shunt palpitation (n)5 (22%)4 (31%)1 (10%)0.67
 Type of RVOT repair at ICR
  Transannular patch (n)9 (39%)5 (38%)3 (30%)0.45
  Commissurotomy + RV patch (n)6 (26%)5 (38%)6 (60%)
  Commissurotomy (n)8 (35%)3 (23%)1 (10%)
  Catheter ablation before PVR (n)1 (4%)1 (8%)3 (30%)0.073
  Atrial tachyarrhythmia (PAT, PAF, AFL) (n)8 (35%)3 (23%)5 (50%)0.7
  Sick sinus syndrome (n)2 (9%)1 (8%)1 (10%)1.0
Intraoperative characteristics
 ECC time at PVR (min)164 (53)146 (43)160 (55)0.61
 Ao XCl at PVR (n)15 (65%)5 (38%)5 (50%)0.36
 Ao XCl time at PVR (min)86 (36)90 (38)97 (32)0.82
 Type of valve

Bovine: 19 (83%)

Porcine: 2 (8.7%)

DC: 2 (8.7%)

Bovine: 6 (46%)

Porcine: 4 (31%)

DC: 3 (23%)

Bovine: 7 (70%)

Porcine 3 (30%)

0.10
 Valve size (mm)23 [23–25]23 [23–25.5]22 [21–23]0.074
 Concomitant procedure
 TV surgery (n)16 (70%)6 (46%)7 (70%)0.37
 Maze procedure (n)8 (34%)2 (15%)4 (40%)0.46
 Pacemaker implantation (n)2 (9%)1 (8%)1 (10%)1
Group (−) [n = 23]Group (+, −) [n = 13]Group (+, +) [n = 10]P-value
Baseline characteristics
 Male to female ratio13:107:62:80.15
 Age at PVR (years)35 (10)37 (13)40 (16)0.51
 Age at initial repair (years)2.5 [2–5]3 [2–5.4]3.1 [2.1–10]0.75
 Interval from initial repair to PVR (years)30 (8)33 (11)33 (11)0.6
 Previous shunt palpitation (n)5 (22%)4 (31%)1 (10%)0.67
 Type of RVOT repair at ICR
  Transannular patch (n)9 (39%)5 (38%)3 (30%)0.45
  Commissurotomy + RV patch (n)6 (26%)5 (38%)6 (60%)
  Commissurotomy (n)8 (35%)3 (23%)1 (10%)
  Catheter ablation before PVR (n)1 (4%)1 (8%)3 (30%)0.073
  Atrial tachyarrhythmia (PAT, PAF, AFL) (n)8 (35%)3 (23%)5 (50%)0.7
  Sick sinus syndrome (n)2 (9%)1 (8%)1 (10%)1.0
Intraoperative characteristics
 ECC time at PVR (min)164 (53)146 (43)160 (55)0.61
 Ao XCl at PVR (n)15 (65%)5 (38%)5 (50%)0.36
 Ao XCl time at PVR (min)86 (36)90 (38)97 (32)0.82
 Type of valve

Bovine: 19 (83%)

Porcine: 2 (8.7%)

DC: 2 (8.7%)

Bovine: 6 (46%)

Porcine: 4 (31%)

DC: 3 (23%)

Bovine: 7 (70%)

Porcine 3 (30%)

0.10
 Valve size (mm)23 [23–25]23 [23–25.5]22 [21–23]0.074
 Concomitant procedure
 TV surgery (n)16 (70%)6 (46%)7 (70%)0.37
 Maze procedure (n)8 (34%)2 (15%)4 (40%)0.46
 Pacemaker implantation (n)2 (9%)1 (8%)1 (10%)1

Continuous data are presented as mean (standard deviation) or median [interquartile range], while categorical data are shown as the number (percentage) of observations. The statistical analysis was performed using one-way analysis of variance followed by the Tukey–Kramer or the Kruskal–Wallis test with a post hoc comparison using the Dwass post hoc test for multiple comparisons, or the Cochran–Armitage trend test.

AFL: atrial flutter; Ao XCl: aortic cross-clamping; Bovine: bovine pericardial valve; DC: decellularized homograft; ECC: extracorporeal circulation; ICR: intracardiac repair; PAF: paroxysmal atrial fibrillation; PAT: paroxysmal atrial tachycardia; Porcine: porcine valve; PVR: pulmonary valve replacement; RV: right ventricle; RVOT: right ventricular outflow tract; TV: tricuspid valve.

Comparison of preoperative haemodynamic parameters and volume between the study groups

There was no significant between-group difference in RV end-diastolic volume index. However, the RVESVI and right atrial volume index were greater in group (+, +) than in group (−). Furthermore, the RVEDP and % RV fibrosis in group (+, +) were greater than in the other 2 groups [8.0 (standard deviation 2.7) in group (−) vs 7.9 (3.0) in group (+, −) vs 11 (2.0) mmHg in group (+, +), P = 0.003 and 13 (5.2) vs 11 (3.0) vs 21 (4.4), P = 0.001, respectively; Table 3].

Table 3:
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The comparison of preoperative patient characteristics

Group (−) (n = 23)Group (+, −) (n = 13)Group (+, +) (n = 10)P-value
RVEDVI (ml/m2)156 (44)153 (30)181 (33)0.18
RVESVI (ml/m2)86 (28)94 (19)112 (27)*0.038
RVEF (%)45 (10)38 (8.1)37 (12)0.097
RVSP (mmHg)44 (13)46 (14)48 (18)0.67
RVEDP (mmHg)8.0 (2.7)7.9 (3.0)11 (2.0)*†0.003
PG (PA-RV) (mmHg)11 [5–25]10 [5–15]4 [2–36]0.91
Mean PAP (mmHg)15 (3.2)16 (3.6)16 (3.2)0.58
PVRI (unit/m2)2.1 (1.1)2.0 (1.1)2.3 (0.9)0.81
RAVI (ml/m2)70 (20)77 (17)92 (20)*0.018
RAP (mmHg)7.3 (2.2)7.6 (3.2)9.5 (2.4)0.078
%fibrosis of RV13 (5.2) (n = 17)11 (3.0) (n = 9)21 (4.4)*† (n = 7)0.001
TR ≥ mild (n)14 (61%)7 (54%)7 (70%)0.85
LVEF (%)49 (7)51 (8)48 (11)0.55
PCWP (mmHg)9.6 (2.1)9.8 (2.5)11 (2.8)0.12
QRS duration (ms)145 (29)155 (24)150 (19)0.56
Group (−) (n = 23)Group (+, −) (n = 13)Group (+, +) (n = 10)P-value
RVEDVI (ml/m2)156 (44)153 (30)181 (33)0.18
RVESVI (ml/m2)86 (28)94 (19)112 (27)*0.038
RVEF (%)45 (10)38 (8.1)37 (12)0.097
RVSP (mmHg)44 (13)46 (14)48 (18)0.67
RVEDP (mmHg)8.0 (2.7)7.9 (3.0)11 (2.0)*†0.003
PG (PA-RV) (mmHg)11 [5–25]10 [5–15]4 [2–36]0.91
Mean PAP (mmHg)15 (3.2)16 (3.6)16 (3.2)0.58
PVRI (unit/m2)2.1 (1.1)2.0 (1.1)2.3 (0.9)0.81
RAVI (ml/m2)70 (20)77 (17)92 (20)*0.018
RAP (mmHg)7.3 (2.2)7.6 (3.2)9.5 (2.4)0.078
%fibrosis of RV13 (5.2) (n = 17)11 (3.0) (n = 9)21 (4.4)*† (n = 7)0.001
TR ≥ mild (n)14 (61%)7 (54%)7 (70%)0.85
LVEF (%)49 (7)51 (8)48 (11)0.55
PCWP (mmHg)9.6 (2.1)9.8 (2.5)11 (2.8)0.12
QRS duration (ms)145 (29)155 (24)150 (19)0.56

Continuous data are presented as mean (standard deviation) or median [interquartile range], while categorical data are shown as the number (percentage) of observations. The statistical analysis was performed using one-way analysis of variance followed by the Tukey–Kramer or the Kruskal–Wallis test with a post hoc comparison using the Dwass post hoc test for multiple comparisons, or using the Cochran–Armitage trend test.

*

P < 0.05: group (−) vs group (+/+),

†

P < 0.05: group (+/−) vs group (+/+).

LVEF: left ventricular ejection fraction; PAP: pulmonary artery pressure; PCWP: pulmonary capillary wedge pressure; PG (PA-RV): pressure gradient between pulmonary artery and right ventricle; PVRI; pulmonary vascular resistance index; RAP: right atrial pressure; RAVI: right atrial volume index; RV: right ventricle; RVEDP: right ventricular end-diastolic pressure; RVEDVI: right ventricular end-diastolic volume index; RVEF: right ventricular ejection fraction; RVESVI: right ventricular end-systolic volume index; RVSP: right ventricular systolic pressure; TR: tricuspid regurgitation.

Table 3:
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The comparison of preoperative patient characteristics

Group (−) (n = 23)Group (+, −) (n = 13)Group (+, +) (n = 10)P-value
RVEDVI (ml/m2)156 (44)153 (30)181 (33)0.18
RVESVI (ml/m2)86 (28)94 (19)112 (27)*0.038
RVEF (%)45 (10)38 (8.1)37 (12)0.097
RVSP (mmHg)44 (13)46 (14)48 (18)0.67
RVEDP (mmHg)8.0 (2.7)7.9 (3.0)11 (2.0)*†0.003
PG (PA-RV) (mmHg)11 [5–25]10 [5–15]4 [2–36]0.91
Mean PAP (mmHg)15 (3.2)16 (3.6)16 (3.2)0.58
PVRI (unit/m2)2.1 (1.1)2.0 (1.1)2.3 (0.9)0.81
RAVI (ml/m2)70 (20)77 (17)92 (20)*0.018
RAP (mmHg)7.3 (2.2)7.6 (3.2)9.5 (2.4)0.078
%fibrosis of RV13 (5.2) (n = 17)11 (3.0) (n = 9)21 (4.4)*† (n = 7)0.001
TR ≥ mild (n)14 (61%)7 (54%)7 (70%)0.85
LVEF (%)49 (7)51 (8)48 (11)0.55
PCWP (mmHg)9.6 (2.1)9.8 (2.5)11 (2.8)0.12
QRS duration (ms)145 (29)155 (24)150 (19)0.56
Group (−) (n = 23)Group (+, −) (n = 13)Group (+, +) (n = 10)P-value
RVEDVI (ml/m2)156 (44)153 (30)181 (33)0.18
RVESVI (ml/m2)86 (28)94 (19)112 (27)*0.038
RVEF (%)45 (10)38 (8.1)37 (12)0.097
RVSP (mmHg)44 (13)46 (14)48 (18)0.67
RVEDP (mmHg)8.0 (2.7)7.9 (3.0)11 (2.0)*†0.003
PG (PA-RV) (mmHg)11 [5–25]10 [5–15]4 [2–36]0.91
Mean PAP (mmHg)15 (3.2)16 (3.6)16 (3.2)0.58
PVRI (unit/m2)2.1 (1.1)2.0 (1.1)2.3 (0.9)0.81
RAVI (ml/m2)70 (20)77 (17)92 (20)*0.018
RAP (mmHg)7.3 (2.2)7.6 (3.2)9.5 (2.4)0.078
%fibrosis of RV13 (5.2) (n = 17)11 (3.0) (n = 9)21 (4.4)*† (n = 7)0.001
TR ≥ mild (n)14 (61%)7 (54%)7 (70%)0.85
LVEF (%)49 (7)51 (8)48 (11)0.55
PCWP (mmHg)9.6 (2.1)9.8 (2.5)11 (2.8)0.12
QRS duration (ms)145 (29)155 (24)150 (19)0.56

Continuous data are presented as mean (standard deviation) or median [interquartile range], while categorical data are shown as the number (percentage) of observations. The statistical analysis was performed using one-way analysis of variance followed by the Tukey–Kramer or the Kruskal–Wallis test with a post hoc comparison using the Dwass post hoc test for multiple comparisons, or using the Cochran–Armitage trend test.

*

P < 0.05: group (−) vs group (+/+),

†

P < 0.05: group (+/−) vs group (+/+).

LVEF: left ventricular ejection fraction; PAP: pulmonary artery pressure; PCWP: pulmonary capillary wedge pressure; PG (PA-RV): pressure gradient between pulmonary artery and right ventricle; PVRI; pulmonary vascular resistance index; RAP: right atrial pressure; RAVI: right atrial volume index; RV: right ventricle; RVEDP: right ventricular end-diastolic pressure; RVEDVI: right ventricular end-diastolic volume index; RVEF: right ventricular ejection fraction; RVESVI: right ventricular end-systolic volume index; RVSP: right ventricular systolic pressure; TR: tricuspid regurgitation.

Comparison of post-pulmonary valve replacement course

The course post-PVR is shown in Table 4. During follow-up, one patient in group (−) died due to thyroid crisis and one in group (+, +) died as a result of hepatic cirrhosis. Although concomitant redo-PVR were performed in 2 patients due to severe aortic regurgitation, there was no prosthetic valve dysfunction that included greater than moderate pulmonary regurgitation or pulmonary stenosis with a peak transvalvular velocity of more than 3.0 m/s. Post-PVR atrial tachyarrhythmia, development of sick sinus syndrome de novo or atrioventricular block more than grade II, pacemaker implantation after PVR and the incidence of hospitalization associated with cardiac lesions were most common in group (+, +). Five patients had recurrent atrial tachyarrhythmia and 3 patients developed this arrhythmia de novo (Fig. 3). At 1 year after PVR, the RV end-diastolic volume index was greater in group (+, +) than in the other 2 groups and the RVESVI was greater in group (+, +) than in group (−).

Freedom from atrial tachyarrhythmia. Red line showed group (−), green line showed group (+, −) and blue line showed group (+, +).
Figure 3:

Freedom from atrial tachyarrhythmia. Red line showed group (−), green line showed group (+, −) and blue line showed group (+, +).

Open in new tabDownload slide
Table 4:
Open in new tab

The comparison of postoperative patient characteristics

Group (−) (n = 23)Group (+, −) (n = 13)Group (+, +) (n = 10)P-value
Post-PVR follow-up period (year)7.6 (3.4)5.9 (4.0)5.1 (1.9)0.09
Death (n)1 (non-cardiac death)01 (non-cardiac death)
Redo PVR (n)1 (concomitant PVR)01 (concomitant PVR)
Post-PVR atrial tachyarrhythmia (n)1 (4%, relapse 1)1 (8%, relapse 1)8 (80%, relapse 5, de novo 3)*†<0.001
Post-PVR ablation (n)1 (4%)1 (8%)3 (30%)0.073
Novel SSS or AVB≧Ⅱ (n)4 (17%)2 (15%)6 (60%)*†0.023
Pacemaker implantation after PVR (n)3 (13%)1 (8%)5 (50%)*0.040
Hospitalization (event/5 years)0 [0–0]0 [0–0.17]1.4 [0–2.1]*0.009
RVEDVI 1 y after PVR (ml/m2)100 (24)105 (23)131 (25)*†0.004
 ΔRVEDVI (pre-1 year) (ml/m2)57 (37)48 (24)49 (39)0.73
RVESVI 1 year after PVR (ml/m2)55 (16)67 (16)77 (29)*0.011
 ΔRVESVI (pre-1 year) (ml/m2)31 (22)27 (19)34 (28)0.72
LVEF 1 year after PVR (ml/m2)56 (7.5)56 (7.4)57 (8.7)0.96
Group (−) (n = 23)Group (+, −) (n = 13)Group (+, +) (n = 10)P-value
Post-PVR follow-up period (year)7.6 (3.4)5.9 (4.0)5.1 (1.9)0.09
Death (n)1 (non-cardiac death)01 (non-cardiac death)
Redo PVR (n)1 (concomitant PVR)01 (concomitant PVR)
Post-PVR atrial tachyarrhythmia (n)1 (4%, relapse 1)1 (8%, relapse 1)8 (80%, relapse 5, de novo 3)*†<0.001
Post-PVR ablation (n)1 (4%)1 (8%)3 (30%)0.073
Novel SSS or AVB≧Ⅱ (n)4 (17%)2 (15%)6 (60%)*†0.023
Pacemaker implantation after PVR (n)3 (13%)1 (8%)5 (50%)*0.040
Hospitalization (event/5 years)0 [0–0]0 [0–0.17]1.4 [0–2.1]*0.009
RVEDVI 1 y after PVR (ml/m2)100 (24)105 (23)131 (25)*†0.004
 ΔRVEDVI (pre-1 year) (ml/m2)57 (37)48 (24)49 (39)0.73
RVESVI 1 year after PVR (ml/m2)55 (16)67 (16)77 (29)*0.011
 ΔRVESVI (pre-1 year) (ml/m2)31 (22)27 (19)34 (28)0.72
LVEF 1 year after PVR (ml/m2)56 (7.5)56 (7.4)57 (8.7)0.96

Continuous data are presented as mean (standard deviation) or median [interquartile range], while categorical data are shown as the number (percentage) of observations. Two patients underwent concomitant PVR at AVR for severe AR. The statistical analysis was performed using one-way analysis of variance followed by the Tukey–Kramer or the Kruskal–Wallis test with a post hoc comparison using the Dwass post hoc test for multiple comparisons, or using the Cochran–Armitage trend test.

*

P < 0.05: group (−) vs group (+/+),

†

P < 0.05: group (+/−) vs group (+/+).

AR: aortic regurgitation; AVB: atrioventricular block; AVR: aortic valve replacement; LVEF: left ventricular ejection fraction; PVR: pulmonary valve replacement; RAVI: right atrial volume index; RVEDVI: right ventricular end-diastolic volume index; RVESVI: right ventricular end-systolic volume index; SSS: sick sinus syndrome.

Table 4:
Open in new tab

The comparison of postoperative patient characteristics

Group (−) (n = 23)Group (+, −) (n = 13)Group (+, +) (n = 10)P-value
Post-PVR follow-up period (year)7.6 (3.4)5.9 (4.0)5.1 (1.9)0.09
Death (n)1 (non-cardiac death)01 (non-cardiac death)
Redo PVR (n)1 (concomitant PVR)01 (concomitant PVR)
Post-PVR atrial tachyarrhythmia (n)1 (4%, relapse 1)1 (8%, relapse 1)8 (80%, relapse 5, de novo 3)*†<0.001
Post-PVR ablation (n)1 (4%)1 (8%)3 (30%)0.073
Novel SSS or AVB≧Ⅱ (n)4 (17%)2 (15%)6 (60%)*†0.023
Pacemaker implantation after PVR (n)3 (13%)1 (8%)5 (50%)*0.040
Hospitalization (event/5 years)0 [0–0]0 [0–0.17]1.4 [0–2.1]*0.009
RVEDVI 1 y after PVR (ml/m2)100 (24)105 (23)131 (25)*†0.004
 ΔRVEDVI (pre-1 year) (ml/m2)57 (37)48 (24)49 (39)0.73
RVESVI 1 year after PVR (ml/m2)55 (16)67 (16)77 (29)*0.011
 ΔRVESVI (pre-1 year) (ml/m2)31 (22)27 (19)34 (28)0.72
LVEF 1 year after PVR (ml/m2)56 (7.5)56 (7.4)57 (8.7)0.96
Group (−) (n = 23)Group (+, −) (n = 13)Group (+, +) (n = 10)P-value
Post-PVR follow-up period (year)7.6 (3.4)5.9 (4.0)5.1 (1.9)0.09
Death (n)1 (non-cardiac death)01 (non-cardiac death)
Redo PVR (n)1 (concomitant PVR)01 (concomitant PVR)
Post-PVR atrial tachyarrhythmia (n)1 (4%, relapse 1)1 (8%, relapse 1)8 (80%, relapse 5, de novo 3)*†<0.001
Post-PVR ablation (n)1 (4%)1 (8%)3 (30%)0.073
Novel SSS or AVB≧Ⅱ (n)4 (17%)2 (15%)6 (60%)*†0.023
Pacemaker implantation after PVR (n)3 (13%)1 (8%)5 (50%)*0.040
Hospitalization (event/5 years)0 [0–0]0 [0–0.17]1.4 [0–2.1]*0.009
RVEDVI 1 y after PVR (ml/m2)100 (24)105 (23)131 (25)*†0.004
 ΔRVEDVI (pre-1 year) (ml/m2)57 (37)48 (24)49 (39)0.73
RVESVI 1 year after PVR (ml/m2)55 (16)67 (16)77 (29)*0.011
 ΔRVESVI (pre-1 year) (ml/m2)31 (22)27 (19)34 (28)0.72
LVEF 1 year after PVR (ml/m2)56 (7.5)56 (7.4)57 (8.7)0.96

Continuous data are presented as mean (standard deviation) or median [interquartile range], while categorical data are shown as the number (percentage) of observations. Two patients underwent concomitant PVR at AVR for severe AR. The statistical analysis was performed using one-way analysis of variance followed by the Tukey–Kramer or the Kruskal–Wallis test with a post hoc comparison using the Dwass post hoc test for multiple comparisons, or using the Cochran–Armitage trend test.

*

P < 0.05: group (−) vs group (+/+),

†

P < 0.05: group (+/−) vs group (+/+).

AR: aortic regurgitation; AVB: atrioventricular block; AVR: aortic valve replacement; LVEF: left ventricular ejection fraction; PVR: pulmonary valve replacement; RAVI: right atrial volume index; RVEDVI: right ventricular end-diastolic volume index; RVESVI: right ventricular end-systolic volume index; SSS: sick sinus syndrome.

Risk factors for development of atrial tachyarrhythmia

A multivariate Cox regression model identified the risk factors for atrial tachyarrhythmia after PVR to be persistent EDFF (hazard ratio 29, 95% confidence interval 4.7–560; P < 0.001) and RVEDP (hazard ratio 1.7, 95% confidence interval 1.1–2.8; P = 0.010; Table 5).

Table 5:
Open in new tab

Risk analysis for atrial tachyarrhythmia after PVR

Univariate
Multivariate
HR (95% CI)P-valueHR (95% CI)P-value
Persistent EDFFa45 (7.9–858)<0.00129 (4.7–560)<0.001
RVEDP (mmHg)1.8 (1.3–2.7)0.0021.7 (1.1–2.8)0.010
RAVI (ml/m2)1.05 (1.0–1.09)0.004
Univariate
Multivariate
HR (95% CI)P-valueHR (95% CI)P-value
Persistent EDFFa45 (7.9–858)<0.00129 (4.7–560)<0.001
RVEDP (mmHg)1.8 (1.3–2.7)0.0021.7 (1.1–2.8)0.010
RAVI (ml/m2)1.05 (1.0–1.09)0.004
a

The number at risk of persistent EDFF was 10 and the incidence of atrial tachyarrhythmia was 8.

CI: confidence interval; EDFF: pulmonary end-diastolic forward flow; HR: hazard ratio; RAVI: right atrial volume index; RVEDP: right ventricular end-diastolic pressure.

Table 5:
Open in new tab

Risk analysis for atrial tachyarrhythmia after PVR

Univariate
Multivariate
HR (95% CI)P-valueHR (95% CI)P-value
Persistent EDFFa45 (7.9–858)<0.00129 (4.7–560)<0.001
RVEDP (mmHg)1.8 (1.3–2.7)0.0021.7 (1.1–2.8)0.010
RAVI (ml/m2)1.05 (1.0–1.09)0.004
Univariate
Multivariate
HR (95% CI)P-valueHR (95% CI)P-value
Persistent EDFFa45 (7.9–858)<0.00129 (4.7–560)<0.001
RVEDP (mmHg)1.8 (1.3–2.7)0.0021.7 (1.1–2.8)0.010
RAVI (ml/m2)1.05 (1.0–1.09)0.004
a

The number at risk of persistent EDFF was 10 and the incidence of atrial tachyarrhythmia was 8.

CI: confidence interval; EDFF: pulmonary end-diastolic forward flow; HR: hazard ratio; RAVI: right atrial volume index; RVEDP: right ventricular end-diastolic pressure.

DISCUSSION

The main findings of this study were as follows. First, a higher preoperative RVEDP, a larger right atrial volume index and greater % RV fibrosis were observed in patients with persistent EDFF. Second, these patients had a higher incidence of postoperative atrial tachyarrhythmia, sick sinus syndrome de novo, atrioventricular block more than grade II, a greater likelihood of needing pacemaker implantation after PVR and a higher hospitalization rate. Third, a multivariate Cox regression model showed that persistent EDFF was a risk factor for development of atrial tachyarrhythmia after PVR.

The observation of EDFF in the main pulmonary artery in patients with repaired TOF has been regarded as a complex phenomenon associated with decreased RV compliance, the grade of pulmonary regurgitation, the size of the RV and the contractile efficiency of the RA [8, 14–16]. This finding has been postulated to be a manifestation of unfavourable haemodynamics in repaired TOF and proposed as a marker of a potential adverse functional outcome and a risk factor for mortality or cardiac transplantation [10, 21]. However, the association between EDFF and the prognosis late after PVR in patients with repaired TOF remains unclear. The previous studies included patients who underwent cardiac MRI or catheterization that was not associated with the timing of PVR [11, 12, 14–16, 22]. Most of those studies of EDFF evaluated cardiac function in patients with pulmonary valve incompetence, which made it difficult to assess the function of the RV itself. In our study, the data were also analysed after PVR, when the impact of pulmonary regurgitation did not affect the presence of EDFF.

In our study, there was no difference in major adverse outcomes, including death or need for redo PVR, between the 3 groups. However, patients with persistent EDFF had a high incidence of arrhythmic events. Our results suggest that EDFF with restrictive signs such as a high RVEDP, a large RVESVI, a large right atrial volume index and high grade of RV fibrosis predisposes to the development of atrial arrhythmic events. The pathophysiological cause of RV restriction is an increase in RVEDP due to increased myocardial fibrosis and decreased RV compliance [1, 2]. This restriction in RV results in a high RA burden. Several reports have shown that patients with a high RA pressure, a large RA volume, a high RVEDP or a high RV extracellular matrix volume have adverse clinical outcomes, including supraventricular arrhythmia [1, 7, 23]. Post-PVR atrial tachyarrhythmia has been reported to be a risk factor for an adverse clinical outcome, including sustained ventricular tachycardia or heart failure [24, 25]. It can be presumed from our findings and previous reports that patients with persistent EDFF have a poor prognosis.

Our results suggest that persistent EDFF can potentially be used for risk stratification and prognostication after PVR in patients with repaired TOF and can complement the current risk stratification based primarily on RV volumes. In patients who are late after repaired TOF, examination for EDFF by Doppler echocardiography is non-invasive. EDFF could be a useful guide for the decision to performing more detailed examinations, such as cardiac MRI, cardiac catheterization and Holter electrocardiography. Moreover, persistent EDFF after PVR is effective for identification of the patient population with repaired TOF and preoperative EDFF who have a poor prognosis after PVR. Close follow-up of patients with persistent EDFF and early detection of adverse events using persistent EDFF as one of the markers of an adverse clinical outcome after PVR are important.

Furthermore, our patients with EDFF preoperatively that resolved after PVR had a prognosis that was as good as that of their counterparts without EDFF. Although the previous reports have suggested that patients with EDFF can be divided into 2 populations according to RV compliance, they did not refer to the prognosis in these 2 groups or define the threshold for division of the groups [14, 16]. We have also identified the characteristics of patients with EDFF who showed restrictive RV physiology by examining the characteristics of those with persistent EDFF. Our results suggest that RVEDP and grade of RV fibrosis could be the threshold for dividing patients with EDFF into those with a good prognosis and those with a poor prognosis in terms of arrhythmia.

Residual PI and tricuspid regurgitation should be considered when evaluating the impact of persistent EDFF on the prognosis after PVR. There was no significant paravalvular leak in any of our 46 patients during the study period. Residual PI gradually developed when transvalvular leak was present. Although no patient showed evidence of severe PI, 5 patients had moderate PI [2 in EDFF group (−), one in EDFF group (+/−) and 2 in EDFF group (+/+), P = 0.57] during the study period. The number of patients with more than moderate PI was so small that we could not find a significant relationship between residual PI, EDFF/atrial fibrillation and RV reverse remodelling. Moreover, no patient showed more than moderate TR after PVR during the study period. In this study, residual PI and TR had little influence on the incidence of atrial tachyarrhythmia after PVR.

Limitations

This study has several limitations, in particular a small sample size and a retrospective, long-term, single-centre design. Therefore, it may have lacked sufficient statistical power to be able to draw firm conclusions. Second, the histological findings on RV myocardial biopsy were based on data from 33 patients. Third, we could not assess the EDFF in patients with permanent AF and had to exclude them from the study. Fourth, because patients with a pacemaker in this cohort could not undergo cardiac MRI, we could not fully examine the correlation between the analysis of EDFF using echocardiography and that obtained by cardiac MRI.

CONCLUSION

Persistent EDFF after PVR could herald a worse prognosis, especially in terms of atrial tachyarrhythmia, in patients with repaired TOF. Close outpatient follow-up is required for early detection of arrhythmia and a prompt decision regarding the need for reintervention.

Presented at the 34th Annual Meeting of the European Association for Cardio-Thoracic Surgery, Barcelona, Spain, 8–10 October 2020.

ACKNOWLEDGEMENTS

The authors would like to thank Editage (www.editage.jp) for English language editing.

Conflict of interest: none declared.

Author contributions

Yuji Tominaga: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Project administration; Writing—original draft. Masaki Taira: Supervision; Writing—review & editing. Takashi Kido: Conceptualization; Data curation; Formal analysis; Project administration; Writing—review & editing. Tomomitsu Kanaya: Data curation; Methodology. Kanta Araki: Conceptualization; Methodology. Takuji Watanabe: Conceptualization; Data curation. Ryoto Sakaniwa: Formal analysis. Koichi Toda: Supervision. Toru Kuratani: Supervision. Takayoshi Ueno: Supervision; Validation. Yoshiki Sawa: Supervision.

Reviewer information

European Journal of Cardio-Thoracic Surgery thanks Krishnasamy Arunkumar, Keiichi Itatani, Shahab Nozohoor and the other anonymous reviewers for their contribution to the peer review process of this article.

REFERENCES

1

Chen
CA
,
Dusenbery
SM
,
Valente
AM
,
Powell
AJ
,
Geva
T.
Myocardial ECV fraction assessed by CMR is associated with type of hemodynamic load and arrhythmia in repaired tetralogy of Fallot
.
JACC Cardiovasc Imaging
2016
;
9
:
1
–
10
.

Google Scholar

Crossref
Search ADS
PubMed

 
2

Yamamura
K
,
Yuen
D
,
Hickey
EJ
,
He
X
,
Chaturvedi
RR
,
Friedberg
MK
 et al.
Right ventricular fibrosis is associated with cardiac remodelling after pulmonary valve replacement
.
Heart
2019
;
105
:
855
–
63
.

Google Scholar

Crossref
Search ADS
PubMed

 
3

Oosterhof
T
,
van Straten
A
,
Vliegen
HW
,
Meijboom
FJ
,
van Dijk
APJ
,
Spijkerboer
AM
 et al.
Preoperative thresholds for pulmonary valve replacement in patients with corrected tetralogy of Fallot using cardiovascular magnetic resonance
.
Circulation
2007
;
116
:
545
–
51
.

Google Scholar

Crossref
Search ADS
PubMed

 
4

Heng
EL
,
Gatzoulis
MA
,
Uebing
A
,
Sethia
B
,
Uemura
H
,
Smith
GC
 et al.
Immediate and midterm cardiac remodeling after surgical pulmonary valve replacement in adults with repaired tetralogy of Fallot: a prospective cardiovascular magnetic resonance and clinical study
.
Circulation
2017
;
136
:
1703
–
13
.

Google Scholar

Crossref
Search ADS
PubMed

 
5

Stout
KK
,
Daniels
CJ
,
Aboulhosn
JA
,
Bozkurt
B
,
Broberg
CS
,
Colman
JM
 et al.
2018 AHA/ACC guideline for the management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines
.
Circulation
2019
;
139
:
e698
–
800
.

Google Scholar

PubMed
OpenURL Placeholder Text

 
6

Egbe
AC
,
Pellikka
PA
,
Miranda
WR
,
Bonnichsen
C
,
Reddy
YNV
,
Borlaug
BA
 et al.
Echocardiographic predictors of severe right ventricular diastolic dysfunction in tetralogy of Fallot: relations to patient outcomes
.
Int J Cardiol
2020
;
306
:
49
–
55
.

Google Scholar

Crossref
Search ADS
PubMed

 
7

Kido
T
,
Ueno
T
,
Taira
M
,
Kanaya
T
,
Okuda
N
,
Toda
K
 et al.
Clinical significance of right atrial volume in patients with repaired tetralogy of Fallot
.
Interact CardioVasc Thorac Surg
2020
;
30
:
296
–
302
.

Google Scholar

PubMed
OpenURL Placeholder Text

 
8

Gatzoulis
MA
,
Clark
AL
,
Cullen
S
,
Newman
CG
,
Redington
AN.
Right ventricular diastolic function 15 to 35 years after repair of tetralogy of Fallot. Restrictive physiology predicts superior exercise performance
.
Circulation
1995
;
91
:
1775
–
81
.

Google Scholar

Crossref
Search ADS
PubMed

 
9

Apitz
C
,
Latus
H
,
Binder
W
,
Uebing
A
,
Seeger
A
,
Bretschneider
C
 et al.
Impact of restrictive physiology on intrinsic diastolic right ventricular function and lusitropy in children and adolescents after repair of tetralogy of Fallot
.
Heart
2010
;
96
:
1837
–
41
.

Google Scholar

Crossref
Search ADS
PubMed

 
10

Lu
JC
,
Cotts
TB
,
Agarwal
PP
,
Attili
AK
,
Dorfman
AL.
Relation of right ventricular dilation, age of repair, and restrictive right ventricular physiology with patient-reported quality of life in adolescents and adults with repaired tetralogy of Fallot
.
Am J Cardiol
2010
;
106
:
1798
–
802
.

Google Scholar

Crossref
Search ADS
PubMed

 
11

Lee
W
,
Yoo
SJ
,
Roche
SL
,
Kantor
P
,
Van Arsdell
G
,
Park
EA
 et al.
Determinants and functional impact of restrictive physiology after repair of tetralogy of Fallot: new insights from magnetic resonance imaging
.
Int J Cardiol
2013
;
167
:
1347
–
53
.

Google Scholar

Crossref
Search ADS
PubMed

 
12

Luijnenburg
SE
,
Peters
RE
,
van der Geest
RJ
,
Moelker
A
,
Roos-Hesselink
JW
,
de Rijke
YB
 et al.
Abnormal right atrial and right ventricular diastolic function relate to impaired clinical condition in patients operated for tetralogy of Fallot
.
Int J Cardiol
2013
;
167
:
833
–
9
.

Google Scholar

Crossref
Search ADS
PubMed

 
13

Pijuan-Domenech
A
,
Pineda
V
,
Castro
MA
,
Sureda-Barbosa
C
,
Ribera
A
,
Cruz
LM
 et al.
"Pulmonary valve replacement diminishes the presence of restrictive physiology and reduces atrial volumes": a prospective study in Tetralogy of Fallot patients
.
Int J Cardiol
2014
;
177
:
261
–
5
.

Google Scholar

Crossref
Search ADS
PubMed

 
14

Mori
Y
,
Murakami
T
,
Inoue
N
,
Kaneko
S
,
Nakashima
Y
,
Koide
M.
Is the presence of end-diastolic forward flow specific for restrictive right ventricular physiology in repaired tetralogy of Fallot?
Int J Cardiol
2017
;
240
:
187
–
93
.

Google Scholar

Crossref
Search ADS
PubMed

 
15

Mercer-Rosa
L
,
Fogel
MA
,
Paridon
SM
,
Rychik
J
,
Yang
W
,
Goldmuntz
E.
Revisiting the end-diastolic forward flow (restrictive physiology) in tetralogy of Fallot: an exercise, echocardiographic, and magnetic resonance study
.
JACC Cardiovasc Imaging
2018
;
11
:
1547
–
8
.

Google Scholar

Crossref
Search ADS
PubMed

 
16

Kutty
S
,
Valente
AM
,
White
MT
,
Hickey
K
,
Danford
DA
,
Powell
AJ
 et al.
Usefulness of pulmonary arterial end-diastolic forward flow late after tetralogy of Fallot repair to predict a "restrictive" right ventricle
.
Am J Cardiol
2018
;
121
:
1380
–
6
.

Google Scholar

Crossref
Search ADS
PubMed

 
17

Kido
T
,
Ueno
T
,
Taira
M
,
Ozawa
H
,
Kanaya
T
,
Okuda
N
 et al.
Stroke volume ratio predicts redilatation of the right ventricle after pulmonary valve replacement
.
Ann Thorac Surg
2017
;
104
:
698
–
703
.

Google Scholar

Crossref
Search ADS
PubMed

 
18

Kido
T
,
Ueno
T
,
Taira
M
,
Ozawa
H
,
Toda
K
,
Kuratani
T
 et al.
Clinical predictors of right ventricular myocardial fibrosis in patients with repaired tetralogy of Fallot
.
Circ J
2018
;
82
:
1149
–
54
.

Google Scholar

Crossref
Search ADS
PubMed

 
19

Khairy
P
,
Van Hare
GF
,
Balaji
S
,
Berul
CI
,
Cecchin
F
,
Cohen
MI
 et al.
PACES/HRS expert consensus statement on the recognition and management of arrhythmias in adult congenital heart disease
.
Can J Cardiol
2014
;
30
:
e1–63
.

Google Scholar

Crossref
Search ADS

 
20

Maceira
AM
,
Cosín-Sales
J
,
Roughton
M
,
Prasad
SK
,
Pennell
DJ.
Reference right atrial dimensions and volume estimation by steady state free precession cardiovascular magnetic resonance
.
J Cardiovasc Magn Reson
2013
;
15
:
29
.

Google Scholar

Crossref
Search ADS
PubMed

 
21

Samyn
MM
,
Kwon
EN
,
Gorentz
JS
,
Yan
K
,
Danduran
MJ
,
Cava
JR
 et al.
Restrictive versus nonrestrictive physiology following repair of tetralogy of Fallot: is there a difference?
J Am Soc Echocardiogr
2013
;
26
:
746
–
55
.

Google Scholar

Crossref
Search ADS
PubMed

 
22

Munkhammar
P
,
Carlsson
M
,
Arheden
H
,
Pesonen
E.
Restrictive right ventricular physiology after tetralogy of Fallot repair is associated with fibrosis of the right ventricular outflow tract visualized on cardiac magnetic resonance imaging
.
Eur Heart J Cardiovasc Imaging
2013
;
14
:
978
–
85
.

Google Scholar

Crossref
Search ADS
PubMed

 
23

Egbe
AC
,
Bonnichsen
C
,
Reddy
YNV
,
Anderson
JH
,
Borlaug
BA.
Pathophysiologic and prognostic implications of right atrial hypertension in adults with tetralogy of Fallot
.
J Am Heart Assoc
2019
;
8
:
e014148
.

Google Scholar

PubMed
OpenURL Placeholder Text

 
24

Egbe
AC
,
Miranda
WR
,
Ammash
NM
,
Ananthaneni
S
,
Sandhyavenu
H
,
Abdelsamid
MF
 et al.
Atrial fibrillation therapy and heart failure hospitalization in adults with tetralogy of Fallot
.
JACC Clin Electrophysiol
2019
;
5
:
618
–
25
.

Google Scholar

Crossref
Search ADS
PubMed

 
25

Pastor
TA
,
Geva
T
,
Lu
M
,
Duarte
VE
,
Drakeley
S
,
Sleeper
LA
 et al.
Relation of right ventricular dilation after pulmonary valve replacement to outcomes in patients with repaired tetralogy of Fallot
.
Am J Cardiol
2020
;
125
:
977
–
81
.

Google Scholar

Crossref
Search ADS
PubMed

 

ABBREVIATIONS

     
  • CT

    Computed tomography

    •  
  • EDFF

    End-diastolic forward flow

    •  
  • MRI

    Magnetic resonance imaging

    •  
  • PI

    Pulmonary valve insufficiency

    •  
  • PVR

    Pulmonary valve replacement

    •  
  • RA

    Right atrial

    •  
  • RV

    Right ventricular

    •  
  • RVESVI

    Right ventricular end-systolic volume index

    •  
  • TOF

    Tetralogy of Fallot

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://dbpia.nl.go.kr/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
Topic:
Subject
Arrhythmias Grown-up Congenital Heart Disease Tetralogy of Fallot
Issue Section:
CONGENITAL
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