Abstract
The changes in tricuspid regurgitation (TR) following transcatheter atrial septal defect (ASD) closure, in relation to preprocedural cardiac rhythms, remain unknown. This study aimed to assess sequential changes in TR after ASD closure based on cardiac rhythms. Patients were categorized as sinus rhythm (SR group, n = 89), SR after catheter ablation for atrial fibrillation (ABL group, n = 14), and permanent atrial fibrillation (AF group, n = 12). Echocardiography was performed at baseline, 1 day, 1 month, and 12 months after the procedure. There were significant differences in age (54.5 ± 17.5 years vs 63.9 ± 12.6 years vs 74.3 ± 8.4 years; p < 0.01) and prevalence of moderate ≥ TR at baseline (44.9% vs 78.6% vs 91.7%; p < 0.01) in the SR, ABL, and AF groups, respectively. The SR group showed significant improvement in TR as early as 1-day postclosure, which persisted at 12 months, whereas the ABL and AF groups exhibited no significant improvements in TR at any point postprocedure. Independent predictors of residual moderate ≥ TR at 12 months included being in the ABL or AF groups and having a higher right atrial volume index (RAVI) at baseline. In conclusion, persistent TR may remain after ASD closure, even for patients who achieve SR postablation and those with permanent AF. This persistence may reflect baseline atrial remodeling, as indicated by larger RAVI, beyond volume unloading after ASD closure. These findings highlight the importance of timely therapeutic interventions and careful monitoring for residual TR following ASD closure, especially in patients with a history of AF.
Graphical Abstract
The left-to-right shunt associated with secundum atrial septal defect (ASD) often results in volume overload of the right heart and pulmonary circulation, which can subsequently lead to tricuspid regurgitation (TR). Transcatheter ASD closure has been established as an effective treatment, with studies showing a reduction in TR severity postprocedure. , However, persistent TR has been reported in nearly half of patients following ASD closure, particularly in those with permanent atrial fibrillation (AF), which has been linked to residual moderate ≥ TR.
Additionally, patients with ASD tend to develop AF at a younger age compared to the general population, with its prevalence reaching up to 50% after the age of 60. Catheter ablation (CA) for AF in patients with unrepaired ASD has proven effective, and combining CA and transcatheter ASD closure may be a viable strategy for managing paroxysmal AF in this population, thereby potentially reducing the recurrence of AF. However, the impact of combining CA and ASD closure on the progression of TR remains unclear. Furthermore, there is limited data on the timeline for TR improvement following ASD closure, particularly in relation to preprocedural cardiac rhythms.
Given that TR severity is associated with poor survival outcomes, irrespective of left ventricular ejection fraction (LVEF) or pulmonary artery pressure, understanding the course of TR after ASD closure is critical for optimizing treatment strategies. Therefore, the aim of this study was to evaluate changes in TR following transcatheter ASD closure, stratified by the following cardiac rhythms at the time of the procedure: sinus rhythm (SR), maintained SR after CA for AF, and permanent AF.
Materials and Methods
Study population
This retrospective observational study screened 115 consecutive adult patients who underwent transcatheter ASD closure between July 2012 and December 2023 at Tokai University Hospital, Kanagawa, Japan. The indications for ASD closure included significant left-to-right shunt, right ventricular (RV) volume overload, and/or clinical symptoms of heart failure. The exclusion criterion was pulmonary arterial hypertension with pulmonary vascular resistance >5.0 Wood units, in accordance with the European Society of Cardiology guidelines. ASD closure was performed using either the Amplatzer Septal Occluder (St. Jude Medical, St. Paul, Minnesota) or the Figulla Flex II (Occlutech GmbH, Jena, Germany), depending on the morphology of the ASD.
Patients were categorized into 3 groups based on their baseline cardiac rhythms: (1) SR group, (2) maintained SR after CA for AF (ABL group), and (3) permanent AF (AF group). The decision to pursue ablation in the ABL group was made by a multidisciplinary heart team, including arrhythmia specialists, after considering factors such as AF duration, left atrial diameter, and patient age. All patients in the ABL group underwent ablation prior to ASD closure and were in SR at the time of the procedure. The study was approved by our institution’s ethical committee (reference number: 24R153), and written informed consent was obtained from all participants.
Data collection
Baseline characteristics and laboratory data were collected prior to transcatheter ASD closure. Transthoracic echocardiography (TTE) assessments were conducted at baseline (before ASD closure) and at follow-up intervals of 1 day, 1 month, and 12 months postprocedure. In particular, data related to the changes in TR and right atrial volume index (RAVI) after CA was collected for the ABL group.
Echocardiographic findings
All participants underwent comprehensive TTE evaluation, including standard 2-dimensional B-mode, M-mode, and Doppler imaging. Conventional echocardiographic parameters were measured in accordance with the American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines. , The left ventricular end-diastolic diameter (LVDd), left ventricular end-systolic diameter (LVDs), and left atrial diameter (LAD) were assessed using M-mode imaging. The LVEF was calculated using the modified Simpson’s method.
The severity of TR was graded using semiquantitative methods based on vena contracta width in the apical 4-chamber and parasternal inflow views as follows: trivial–mild (< 3.0 mm), moderate (3.0–6.9 mm), and severe (≥ 7.0 mm). Mitral regurgitation (MR) was graded using quantitative methods that assessed the proximal isovelocity surface area in the apical 4-chamber view.
Measurements for the tricuspid annulus diameter were obtained from the apical 4-chamber view at end-diastole, and the right atrial volume was measured from the RV-focused 4-chamber view at end-systole. RV dimensions, including basal (RVD1) and mid-level diameters (RVD2), were assessed in an RV-focused 4-chamber view at end-diastole. Doppler echocardiography was utilized to measure stroke volume at 2 locations, along with cross-sectional area measurements, to determine the pulmonary-to-systemic blood flow (Qp/Qs) ratio. The average of 3 beats was used for patients in SR, and a minimum of 5 beats was averaged for patients with AF.
Statistical analysis
Continuous variables with a normal distribution were expressed as mean ± standard deviation, while those with a skewed distribution were presented as median [interquartile range]. Comparisons of normally distributed continuous variables were conducted using Student’s t-test; for skewed data, the Wilcoxon rank-sum test was used for 2-group comparisons and the Kruskal–Wallis test for 3-group comparisons. The chi-squared test or Fisher’s exact test was utilized for comparisons of categorical variables.
Changes in continuous variables over time were analyzed using paired t-tests or 1-way analysis of variance, when appropriate. Factors associated with residual moderate ≥ TR following transcatheter ASD closure were identified through univariable and multivariable logistic regression analyses, with odds ratios (OR) reported alongside 95% confidence intervals. Multivariable analysis was performed to adjust for baseline differences and potential confounding factors. Only variables with p < 0.05 in univariable logistic regression were entered into the multivariable model. All statistical analyses were conducted using JMP software, version 16 (SAS Institute, Inc., Cary, NC, USA). A p-value < 0.05 was considered as statistically significant.
Results
Baseline characteristics
A total of 115 patients were enrolled in this study, as shown in the study flow chart in Figure 1 . At baseline, there were 89 patients (77.4%) in the SR group, 14 patients (12.2%) in the ABL group, and 12 patients (10.4%) in the AF group. Baseline clinical characteristics for these 3 groups are presented in Table 1 . Significant differences were observed in age (54.5 ± 17.5 years, 63.9 ± 12.6 years, 74.3 ± 8.4 years; p < 0.01), male gender distribution (43.8%, 50.0%, 83.3%; p = 0.04), and prevalence of hypertension (30.3%, 71.4%, 41.7%; p = 0.01) between SR, ABL, and AF groups, respectively. No significant differences were found in body surface area, the prevalence of diabetes mellitus, and dyslipidemia among the 3 groups. While there was a statistically significant difference in the history of hospitalization for heart failure, the rate was lower in the SR and AF groups compared to the ABL group (3.4% vs 28.6% vs 8.3%; p < 0.01). In addition, the use of diuretics differed significantly among the groups, with higher usage in the ABL and AF groups compared to the SR group (15.7% in SR vs 57.1% in ABL vs 66.7% in AF; p < 0.01). There were also significant differences in brain natriuretic peptide levels (31.8 [19.1–61.7] pg/mL vs 77.4 [62.9–190.2] pg/mL vs 175.9 [83.8–588.6] pg/mL, respectively; p < 0.01) and the estimated glomerular filtration rate (69.8 ± 18.7 mL/min/1.73m 2 vs 57.4 ± 18.2 mL/min/1.73m 2 vs 54.8 ± 14.4 mL/min/1.73m 2, respectively; p < 0.01) among the 3 groups.
Patient flow chart. ABL = catheter ablation; AF = atrial fibrillation; ASD = atrial septal defect; SR = sinus rhythm.
Table 1
Baseline characteristics
| Variable | All patients ( n = 115) | SR group ( n = 89) | ABL group ( n = 14) | AF group ( n = 12) | p-value |
|---|---|---|---|---|---|
| Age, years | 57.7 ± 17.4 | 54.5 ± 17.5 | 63.9 ± 12.6 | 74.3 ± 8.4 | < 0.01 |
| Males, n (%) | 56 (48.7%) | 39 (43.8%) | 7 (50.0%) | 10 (83.3%) | 0.04 |
| Body surface area, m 2 | 1.61 ± 0.11 | 1.61 ± 0.10 | 1.63 ± 0.22 | 1.62 ± 0.10 | 0.71 |
| Hypertension, n (%) | 42 (36.5%) | 27 (30.3%) | 10 (71.4%) | 5 (41.7%) | 0.01 |
| Diabetes mellitus, n (%) | 11 (9.6%) | 7 (7.9%) | 2 (14.3%) | 2 (16.7%) | 0.51 |
| Dyslipidemia, n (%) | 25 (21.7%) | 18 (20.2%) | 4 (28.6%) | 3 (25.0%) | 0.74 |
| History of HF hospitalization, n (%) | 8 (7.0%) | 3 (3.4%) | 4 (28.6%) | 1 (8.3%) | < 0.01 |
| Diuretics, n (%) | 30 (26.1%) | 14 (15.7%) | 8 (57.1%) | 8 (66.7%) | < 0.01 |
| Laboratory data | |||||
| BNP, pg/mL | 47.3 [20.0–93.2] | 31.8 [19.1–61.7] | 77.4 [62.9–190.2] | 175.9 [83.8–588.6] | < 0.01 |
| eGFR, mL/min/1.73m 2 | 66.7 ± 19.0 | 69.8 ± 18.7 | 57.4 ± 18.2 | 54.8 ± 14.4 | < 0.01 |
| Echocardiographic data | |||||
| Atrial septal defect diameter, mm | 16.8 ± 6.4 | 17.0 ± 6.4 | 15.9 ± 4.8 | 16.7 ± 1.8 | 0.82 |
| Device size, mm | 21.8 ± 6.7 | 22.2 ± 6.5 | 20.9 ± 7.3 | 20.0 ± 7.2 | 0.48 |
| Qp, mL | 102.0 ± 36.2 | 103.7 ± 37.1 | 105.3 ± 35.7 | 86.2 ± 28.9 | 0.27 |
| Qs, mL | 52.0 ± 13.8 | 53.7 ± 11.7 | 50.7 ± 18.0 | 41.8 ± 18.4 | 0.02 |
| Qp/Qs | 2.0 ± 0.8 | 2.0 ± 0.7 | 2.2 ± 0.9 | 2.3 ± 0.9 | 0.29 |
| Left ventricular ejection fraction, % | 66.0 ± 9.5 | 67.2 ± 8.3 | 61.1 ± 13.4 | 62.9 ± 11.5 | 0.04 |
| LVDd, mm | 40.5 ± 5.8 | 40.0 ± 5.0 | 42.6 ± 9.2 | 41.4 ± 6.6 | 0.25 |
| LVDs, mm | 25.6 ± 5.4 | 25.0 ± 4.5 | 28.4 ± 8.4 | 27.5 ± 6.8 | 0.05 |
| Left atrial diameter, mm | 37.0 ± 7.6 | 35.2 ± 6.0 | 40.5 ± 7.7 | 46.6 ± 9.9 | < 0.01 |
| LAVI, mL/m 2 | 41.4 [35.4–50.5] | 39.3 [32.7–47.5] | 51.9 [42.3–60.5] | 59.3 [40.8–82.9] | < 0.01 |
| RAVI, mL/m 2 | 49.4 [34.1–72.2] | 44.4 [31.5–67.9] | 61.5 [41.9–93.8] | 81.0 [56.7–122.4] | < 0.01 |
| RVD1, mm | 46.0 [41.0–51.7] | 45.0 [40.5–51.2] | 50.4 [44.5–52.1] | 50.0 [43.0–54.0] | 0.08 |
| RVD2, mm | 36.0 [31.0–42.0] | 35.1 [30.5–42.1] | 36.2 [34.8–42.0] | 40.5 [36.0–44.8] | 0.26 |
| Tricuspid annular diameter, mm | 36.0 [31.7–43.0] | 35.0 [31.0–43.0] | 36.5 [31.0–40.5] | 38.9 [34.5–46.0] | 0.12 |
| RVFAC, % | 41.7 ± 7.5 | 42.7 ± 7.2 | 40.6 ± 4.6 | 35.4 ± 9.6 | < 0.01 |
| TAPSE, mm | 22.1 ± 6.0 | 23.2 ± 5.2 | 21.1 ± 5.2 | 15.1 ± 7.8 | < 0.01 |
| E/e′ | 8.5 ± 3.0 | 8.3 ± 2.8 | 9.0 ± 3.4 | 9.5 ± 4.3 | 0.47 |
| TRPG, mmHg | 27.2 [22.3–35.0] | 26.2 [21.5–31.8] | 31.6 [25.5–35.9] | 35.1 [30.1–44.7] | < 0.01 |
| sPAP, mmHg | 32.2 [26.5–40.8] | 30.2 [25.7–37.7] | 34.6 [30.2–42.7] | 41.1 [36.3–51.2] | < 0.01 |
| TR ≥ moderate, n (%) | 62 (53.9) | 40 (44.9) | 11 (78.6) | 11 (91.7) | < 0.01 |
| MR ≥ moderate, n (%) | 10 (8.7) | 3 (3.4) | 1 (7.1) | 6 (50.0) | < 0.01 |
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