Effects of Transcatheter Atrial Septal Defect Closure in Elderly Patients with Long-Standing Persistent Atrial Fibrillation

Effects of Transcatheter Atrial Septal Defect Closure in Elderly Patients with Long-Standing Persistent Atrial Fibrillation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effects of Transcatheter Atrial Septal Defect Closure in Elderly Patients with Long-Standing Persistent Atrial Fibrillation Yuki Matsubara, Michiyo Yamano, Tetsuhiro Yamano, Takeshi Nakamura, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4794373/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Although the safety and efficacy of transcatheter atrial septal defect (ASD) closure has been reported in elderly patients, postprocedural outcomes in elderly patients with long-standing persistent atrial fibrillation (AF) have not been fully assessed. The aim of this study was to elucidate the cardiac remodeling process and symptom improvement after transcatheter ASD closure in elderly patients with AF (AF-ASD) compared to those in sinus rhythm (SR-ASD). Methods We enrolled 52 patients aged > 70 years out of 253 consecutive patients who underwent transcatheter ASD closure. We retrospectively analyzed serial echocardiograms, New York Heart Association (NYHA) functional classification, and plasma brain natriuretic peptide (BNP) levels from baseline to 1 year after the procedure. Results With respect to the right-sided chambers, significant reverse remodeling began immediately after the procedure and continued in both groups up to 1 year after the procedure. Left ventricular augmentation was comparable in both groups. Left atrial volume increase was prominent in the AF-ASD group, with a statistically significant difference compared with the SR-ASD group from 2 days to 1 year after the procedure (all p < 0.05). NYHA functional classification improved in both groups. Plasma BNP levels decreased only in the AF-ASD group from baseline to 1 year (median value [interquartile range], 336.2 pg/mL [145.1–491.4] to 173.8 pg/mL [73.6–261.7], p = 0.032). Conclusion Transcatheter ASD closure is an effective treatment for heart failure in elderly patients with ASD and long-standing persistent AF. atrial septal defect atrial fibrillation elderly patients heart failure Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Atrial septal defect (ASD) is one of the most common congenital heart diseases diagnosed in adulthood because many children and young adults have no obvious symptoms [ 1 , 2 ]. Transcatheter ASD closure is an effective procedure for most patients with secundum ASD. It is well known that cardiac structural changes and hemodynamic improvement occur immediately after the procedure in both pediatric and adult patients [ 3 – 5 ]. However, some elderly patients have developed heart failure after the procedure because the increased left ventricular preload after device closure exacerbates underlying left ventricular diastolic dysfunction [ 6 – 9 ]. The incidence of long-standing persistent atrial fibrillation (AF) is increasing with societal aging. These patients are included at a certain rate among patients with ASD [ 10 , 11 ]. Few studies have reported cardiac remodeling after transcatheter ASD closure in patients with long-standing persistent AF compared with those in sinus rhythm (SR) [ 12 , 13 ]. We aimed to elucidate the structural and hemodynamic changes and clinical outcomes after transcatheter ASD closure in patients with long-standing persistent AF. Methods Subjects We enrolled 64 patients aged > 70 years out of 253 consecutive patients who underwent transcatheter ASD closure and had successful device implantation at our institution from September 2011 to February 2020. Study participants underwent transthoracic echocardiography (TTE) prior to transcatheter closure and up to 1 year after the procedure. Twelve patients were excluded: three had undergone pulmonary vein isolation for AF, eight could not be followed due to the distance from their home to our institution, and one had died of other diseases. A total of 52 patients (median age, 76 years; 30 women) were included in our study. These patients were divided into two groups: those with long-standing persistent AF (AF-ASD) and those with SR (SR-ASD). All study subjects gave written informed consent. Transcatheter ASD device closure Prior to transcatheter closure, all patients underwent transesophageal echocardiography (TEE) to determine the appropriateness of the procedure by assessing all relevant anatomic features such as maximum defect diameter, surrounding rims, and number of defects [ 14 ]. Right heart catheterization was performed to rule out other comorbid structural abnormalities and to measure pulmonary vascular resistance. Transcatheter defect closure was performed under TEE, intracardiac echocardiography, or both TEE and intracardiac echocardiography guidance, as previously reported [ 15 ]. Amplatzer™ Septal Occluder (Abbott Medical, Plymouth, MN, USA) or Figulla Flex II ASD Occluder (Occlutech, Jena, Germany) was implanted in 36 and 16 patients, respectively. Echocardiographic assessment TTE was performed four times: before transcatheter ASD closure, 2 days after closure, 6 months after closure, and 1 year afterward. Comprehensive echocardiograms that included two-dimensional, pulsed-wave, color, and tissue Doppler images were obtained in all patients using a commercially available system (Vivid E9 or Vivid E95; GE HealthCare, Milwaukee, WI, USA). Although the calculation of left atrial (LA) volume in patients undergoing transcatheter ASD closure might have been affected by the area where the implanted device protrudes into the left atrium, the effect varies based on implant shape. Therefore, we avoided the device when we traced the LA border. Left ventricular (LV) end-diastolic diameter, LA volume index, and LV ejection fraction were analyzed for left-sided chambers. For the right-sided chambers, right ventricular (RV) end diastolic area, right atrial (RA) area, and percent fractional area change were assessed [ 16 ]. The severity of atrioventricular valve regurgitation was assessed based on vena contracta width [ 17 ]. The ratio of early diastolic velocity to early diastolic annular velocity (E/e') and tricuspid regurgitation (TR) pressure gradient were used as indices of LV diastolic function and pulmonary hypertension, respectively [ 18 ]. Furthermore, lateral E/e' was used to exclude the direct effect of the implanted ASD device on mitral annular motion [ 6 , 9 ]. The authors affirm that human research participants provided informed consent for publication of the images in Figs. 3 a and 3 b. Assessment of heart failure New York Heart Association (NYHA) functional classification and plasma brain natriuretic peptide (BNP) levels were assessed at baseline and 1 year after the procedure. Plasma BNP levels were measured using a specific immunoradiometric assay (architect BNP-JP, Abbott Japan, Tokyo, Japan). Statistical analysis All normally distributed values are expressed as means ± standard deviation. Non-normally distributed values are expressed as medians and interquartile range. The chi-squared test was performed for categorical variables. Repeated measures analysis of variance followed by post hoc analysis was used for continuous variables. A two-tailed p value < 0.05 was considered statistically significant. The percentage of values at each time point compared to baseline was calculated and compared between the two groups using the unpaired t-test. All statistical analyses were performed using JMP software (version 16, SAS Institute Inc, Cary, NC, USA). Results Patient characteristics and baseline echocardiographic parameters Although there were no significant differences in age, the incidence of symptomatic heart failure and proportion of patients prescribed diuretics were significantly higher in the AF-ASD group than in the SR-ASD group (Table 1 ). Mean pulmonary artery pressure was significantly higher in patients with AF-ASD. Baseline echocardiographic parameters are shown in Table 2 . Although right-sided chambers and LA volume were significantly larger in patients with AF-ASD, biventricular systolic function did not differ between the two groups. The difference of severity in MR and TR were statistically significant. All the etiologies of atrioventricular valve regurgitation equal or more than moderate degree were annular dilatation. Table 1 Baseline Characteristics Variable AF-ASD (n = 17) SR-ASD (n = 35) p-value Age, years * 78 .5 [74.0–82.0] 74.5 [71.8–80.0] 0.207 Female, n (%) 10 (59%) 20 (57%) 0.908 Body surface area, m 2 1.52 ± 0.17 1.49 ± 0.19 0.578 NYHA functional classification ≥ 2, n (%) 17 (100%) 20 (57%) 0.001 Hypertension, n (%) 9 (53%) 15 (43%) 0.494 Dyslipidemia, n (%) 5 (29%) 15 (43%) 0.345 Coronary artery disease, n (%) 1 (6%) 2 (6%) 0.980 Diabetes mellitus, n (%) 3 (18%) 4 (11%) 0.670 Smoking, n (%) 2 (12%) 2 (6%) 0.591 Calcium antagonist, n (%) 6 (35%) 11 (31%) 0.780 Beta-blocker, n (%) 6 (35%) 4 (11%) 0.041 ACE-I/ARB, n (%) 6 (35%) 8 (23%) 0.343 Diuretic, n (%) 13 (76%) 8 (23%) < 0.001 Cardiac catheterization data Qp/Qs * 2.2 [1.8–3.0] 2.5 [2.0–2.8] 0.904 PVR, Wood units * 2.5 [1.5–2.7] 1.6 [1.3–2.1] 0.024 Mean PAP, mmHg * 30 [ 24 – 38 ] 20 [ 17 – 23 ] < 0.001 Maximum ASD size on TEE, mm * 18.5 [13.3–20.8] 17.0 [14.4–20.5] 0.984 Device size, mm * 20.0 [16.3–25.5] 21.0 [18.0–24.0] 0.687 * Values are medians [interquartile range]. ACE-I, angiotensin-converting enzyme inhibitor; AF, atrial fibrillation; ARB, angiotensin receptor blocker; ASD, atrial septal defect; NYHA, New York Heart Association; PAP, pulmonary arterial pressure; PVR, pulmonary vascular resistance; Qp/Qs, ratio of pulmonary blood flow to systemic blood flow; SR, sinus rhythm; TEE, transesophageal echocardiography. Table 2 Baseline Transthoracic Echocardiographic Parameters Variable AF-ASD SR-ASD p-value RV end diastolic area, cm 2 30.5 ± 7.2 25.4 ± 7.1 0.046 RV fraction area change, % 39.9 ± 9.0 41.3 ± 5.6 0.790 RA area, cm 2 32.0 ± 7.1 21.0 ± 1.1 < 0.001 TR pressure gradient, mmHg 35.5 ± 8.9 31.7 ± 12.4 0.148 LV end diastolic diameter, mm 40.6 ± 5.9 37.6 ± 5.3 0.087 LV ejection fraction, % 62.2 ± 5.8 64.6 ± 7.6 0.201 LA volume index, mL/m 2 66.9 ± 10.0 43.5 ± 12.3 < 0.001 E, m/s 0.92 ± 0.21 0.59 ± 0.14 < 0.001 E/e‘ 14.7 ± 4.3 11.8 ± 4.6 0.011 TR vena contracta width, mm 6.9 ± 2.5 5.2 ± 1.9 0.027 MR vena contracta width, mm 3.7 ± 1.3 2.7 ± 0.8 0.002 * Values are presented as mean + SD. AF, atrial fibrillation; ASD, atrial septal defect; E, early diastolic velocity; E/e′, ratio of E to early diastolic annular velocity; LA, left atrial; LV, left ventricular; MR, mitral regurgitation; RA, right atrial; RV, right ventricular; SR, sinus rhythm; TR, tricuspid regurgitation. Remodeling after transcatheter ASD closure Longitudinal changes in the parameters assessed with TTE from baseline to 1 year after the procedure are shown in Figs. 1 and 2 . With respect to the right-sided chambers, significant reverse remodeling began immediately after the procedure and continued in both groups up to 1 year after the procedure (Fig. 1 ). The percentage values of RV and RA areas were not significantly different between patients with AF-ASD and SR-ASD. RV fractional area change did not change significantly over time in the either group. TR pressure gradient decreased significantly in both groups immediately after the procedure; percentage value at 1 year was comparable between the two groups. TR vena contracta width showed comparable improvement in the two groups. The increase in LA volume and LV end-diastolic diameter persisted up to 1 year after the procedure in both groups (Fig. 2 ). In addition, the percentage value of LA volume index was significantly different between the two groups during the follow-up period. The percentage value of LV ejection fraction did not differ between the two groups over time. There were no significant changes in E/e' over the 1-year follow-up period in either group, but there was a transient increase in the SR-ASD group at 2 days after the procedure. Changes in mitral regurgitation vena contracta width at 6 months and 1 year were statistically significant in both groups; these changes were comparable between the two groups. Figure 3 shows representative cases in both groups with a comparable maximum defect size. Although reductions in right-sided chamber parameters were similar in both patients, LA enlargement was more pronounced in a patient with AF-ASD. Heart failure after transcatheter ASD closure Improvement in NYHA functional classification was seen in almost all symptomatic patients in both groups, except for one patient in the AF-ASD group (Fig. 4 ). There were no significant changes in plasma BNP levels over time in patients with SR-ASD (median [interquartile range], 61.6 pg/mL [37.3–99.8] at baseline to 62.6 pg/mL [35.3–93.8] at 1 year, p = 0.371). In contrast, patients with AF-ASD had a significant decrease after ASD closure (336.2 pg/mL [145.1–491.4] to 173.8 pg/mL [73.6–261.7], p = 0.032). Two patients with AF-ASD were hospitalized for decompensated heart failure during the follow-up period. Discussion We investigated the cardiac chamber remodeling process after transcatheter ASD closure in elderly patients with long-standing persistent AF compared with those in SR. Although remodeling of the right-sided chambers and TR improvement were observed in patients with AF-ASD as well as in those with SR-ASD, LA enlargement was prominent only in patients with AF-ASD. Symptoms of heart failure lessened and plasma BNP levels decreased in patients with AF-ASD at 1 year after the procedure. Remodeling of cardiac chambers Chronic volume overload of the right-sided chambers caused by the existence of ASD leads to RV enlargement, RV dysfunction, and might eventually cause chronic heart failure. In addition, chronic RV volume overload in patients with ASD has been reported to cause LV systolic and diastolic dysfunction due to multiple complex factors such as worsening ventricular interdependence [ 20 – 23 ]. Thus, restoration of right-to-left volume balance is the expected goal of ASD closure. Transcatheter ASD closure produces early and pronounced cardiac structural changes that almost completely restore the volume balance between the right and left cardiac chambers [ 3 , 24 , 25 ], i.e., the right heart shrinks and the left heart expands. Remodeling of cardiac chambers began immediately after the procedure and changes continued for 6 months or 1 year after the procedure, but the rate of the process slowed [ 4 , 5 , 26 ]. The sizes of the right-sided chambers at 1 year follow-up compared to normal controls differ depending on the published report [ 26 – 28 ]. Although a reduction in RV size has been reported in all age groups, the degree of reduction was smaller in elderly patients [ 4 ]. Although the changes in ventricular size 2 days after the procedure were not statistically significant except for RV end-diastolic area in SR-ASD, remodeling was observed up to 1 year after the procedure in both our AF-ASD and SR-ASD patients. ASD closure for elderly patients Transcatheter ASD closure is considered an effective alternative to surgery even in elderly patients with multiple comorbidities due to its low complication rate and short hospital stay [ 29 – 31 ]. However, heart failure due to elevated LV filling pressure after transcatheter ASD closure should be considered a complication unique to elderly patients [ 8 , 9 ]. Although the left ventricle is unloaded by interatrial shunt flow and the increase in LV filling pressure is masked before closure in patients with LV diastolic dysfunction, it might become clinically evident after the procedure [ 8 ]. We assessed LV filling pressure prior to the procedure to after the procedure by lateral E/e’. Lateral E/e’ increased 2 days after the procedure in patients with SR-ASD, whereas the changes in the value in patients with AF-ASD during the follow-up period were not statistically significant (Fig. 2 ). Its change was consistent with the change in plasma BNP level in patients with SR-ASD, though the changes from before the procedure to 1 year after the procedure were not statistically significant (Supplementary Table 1). Preprocedural assessment of high-risk patients is important and early initiation of anti-congestive conditioning therapy might be useful [ 9 ]. The number of elderly patients who experience heart failure after the procedure is limited; most patients experience a decrease in their symptoms [ 6 , 29 – 31 ]. Exercise capacity, usually assessed based on NYHA functional classification or maximal oxygen consumption, improved after transcatheter ASD closure even in patients with no or mild symptoms [ 32 ]. Prochownik et al. [ 33 ] reported changes in symptoms from prior to the procedure up to 1 year after the procedure in adult patients. The number of symptomatic patients decreased at 1 month after the procedure and continued to decrease up to 1 year after the procedure. Maximal oxygen consumption increased significantly from baseline to 1 year after the procedure, but the degree of improvement was lower in patients aged > 40 years than in those aged ≤ 40 years. Some authors have reported the efficacy of transcatheter ASD closure in patients with an average age greater than 65 years [ 29 – 31 ]. All of these studies showed significant improvements in physical activity observed approximately 1 year after the procedure compared to baseline, even though the method of assessment differed depending on the study: 6-minute walk test, cardiopulmonary exercise test, or NYHA functional classification. Improvement in mental scores after the procedure has also been reported in elderly patients [ 29 , 31 ]. Transcatheter ASD closure in elderly patients with long-standing persistent AF Compared with age- and gender-matched controls, patients with ASD have a higher incidence of AF, whether or not closure is performed [ 11 ]. Furthermore, the incidence increases with age both before and after the intervention [ 10 , 34 ]. Although the advisability of catheter-based treatment for AF prior to ASD closure has often been discussed [ 35 , 36 ], the consensus opinion on how to proceed or the background of optimal candidates for catheter ablation in ASD patients with AF has not been published [ 35 , 37 ]. In addition, the choice of catheter ablation before transcatheter ASD closure is not always recommended for patients with long duration of AF or prominent left atrial enlargement who are unlikely to benefit from catheter intervention [ 38 – 40 ]. The efficacy of transcatheter ASD closure in patients with long-standing persistent AF without intervention for arrhythmia has rarely been reported. Taniguchi et al. [ 12 ] reported outcomes after transcatheter ASD closure in elderly patients with long-standing persistent AF. Nine patients who underwent transcatheter ASD closure were followed from before the procedure to more than 6 months after the procedure. RV remodeling, assessed based the ratio of RV to LV diameter, improved. NYHA functional classification and plasma BNP levels improved. Another study analyzed chamber remodeling in patients with long-standing persistent AF before and 6 months after the procedure compared to patients in SR [ 13 ]. Patients with AF had a smaller degree of change in right-sided chambers than patients in SR, whereas symptom relief was comparable in both groups during the follow-up period. The patients with AF in their study were significantly older than those in SR (mean age, 68.3 ± 15.4 vs. 47.4 ± 13.9 years), so the effect of age on the remodeling process cannot be excluded [ 4 ]. As in these previous studies, right heart remodeling and relief of heart failure symptoms in our study were also achieved in patients with AF-ASD and were comparable to those with SR-ASD of the same age. The improvement in TR and TR pressure gradient is also favorable, as reported previously [ 12 , 41 , 42 ]. Although LA volume of patients with AF in our study increased after the procedure, the remodeling of the left atrium after transcatheter ASD closure in elderly patients differs across studies [ 30 , 31 , 41 , 43 ]. This might be due to the fact that most studies partially included patients with AF and the number of studies focusing on patients with AF is limited [ 12 , 13 ]. Although LA remodeling might occur after the procedure, transcatheter ASD closure is a useful and acceptable treatment for heart failure in patients who have difficulty maintaining SR. Limitations This study has some limitations. First, this is a retrospective, single-center study with a small number of patients. Further study with a large number of patients is needed. Second, we only estimated the severity of atrioventricular valve regurgitation using a semi-quantitative method. Atrioventricular valve regurgitation was mild, especially mitral regurgitation in the SR-ASD group, so it was difficult to compare severity based on a quantitative method. Finally, we used two-dimensional echocardiographic parameters to assess the right ventricle, which has a complex geometry. However, we used the chamber quantification methods recommended in the guidelines [ 16 ]. Conclusions Transcatheter ASD closure is an effective treatment for heart failure in elderly ASD patients with long-standing persistent AF in terms of reversal of right heart remodeling and lessening of heart failure symptoms. Abbreviations AF, atrial fibrillation ASD, atrial septal defect BNP, brain natriuretic peptide E/e¢, ratio of early diastolic velocity to early diastolic annular velocity LA, left atrial LV, left ventricular NYHA, New York Heart Association RA, right atrial RV, right ventricular SR, sinus rhythm TEE, transesophageal echocardiography TR, tricuspid regurgitation TTE, transthoracic echocardiography Declarations The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests The authors have no relevant financial or non-financial interests to disclose. Ethics approval The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki, as reflected in the prior approval by the ethics committee of Kyoto Prefectural University of Medicine (ERB-C-835-4). Author Contribution Yuki Matsubara: Conceptualization, Methodology, Formal analysis, Investigation, and Writing-Original Draft. 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Jpn Circ J 1996;60(10):758-766. https://doi.org/10.1253/jcj.60.758 Miki T, Yamano T, Yamano M, Nakamura T, Takamatsu K, Ma C, Wakana N, Nakanishi N, Zen K, Shiraishi H, Shirayama T, Matoba S. Favorable changes of left ventricular function in the circumferential direction following transcatheter atrial septal defect closure: a strain imaging study. Int J Cardiovasc Imaging 2021;37(3):903-912. https://doi.org/10.1007/s10554-020-02064-4 Pascotto M, Santoro G, Cerrato F, Caputo S, Bigazzi MC, Iacono C, Carrozza M, Russo MG, Caianiello G, Calabrò R. Time-course of cardiac remodeling following transcatheter closure of atrial septal defect. Int J Cardiol 2006;112(3):348-352. https://doi.org/10.1016/j.ijcard.2005.10.008 Monfredi O, Luckie M, Mirjafari H, Willard T, Buckley H, Griffiths L, Clarke B, Mahadevan VS. Percutaneous device closure of atrial septal defect results in very early and sustained changes of right and left heart function. 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The benefit of atrial septal defect closure in elderly patients. Clin Interv Aging 2014;9:1101-1107. https://doi.org/10.2147/CIA.S62313 Nakagawa K, Akagi T, Taniguchi M, Kijima Y, Goto K, Kusano KF, Itoh H, Sano S. Transcatheter closure of atrial septal defect in a geriatric population. Catheter Cardiovasc Interv 2012;80(1):84-90. https://doi.org/10.1002/ccd.23457 Khan AA, Tan JL, Li W, Dimopoulos K, Spence MS, Chow P, Mullen MJ. The impact of transcatheter atrial septal defect closure in the older population: a prospective study. JACC Cardiovasc Interv 2010;3(3):276-281. https://doi.org/10.1016/j.jcin.2009.12.011 Brochu MC, Baril JF, Dore A, Juneau M, De Guise P, Mercier LA. Improvement in exercise capacity in asymptomatic and mildly symptomatic adults after atrial septal defect percutaneous closure. Circulation 2002;106(14):1821-1826. https://doi.org/10.1161/01.cir.0000029924.90823.e0 Prochownik P, Przewlocki T, Podolec P, Wilkolek P, Sobien B, Gancarczyk U, Podolec N, Komar M. Improvement of physical capacity in patients undergoing transcatheter closure of atrial septal defects. Postepy Kardiol Interwencyjnej 2018;14(1):90-94. https://doi.org/10.5114/aic.2018.74360 Ghosh S, Chatterjee S, Black E, Firmin RK. Surgical closure of atrial septal defects in adults: effect of age at operation on outcome. Heart 2002;88(5):485-487. https://doi.org/10.1136/heart.88.5.485 Wu SJ, Fan YF, Chien CY. Surgical or interventional treatment for adult patients with atrial septal defect and atrial fibrillation: A systemic review and meta-analysis. Asian J Surg 2022;45(1):62-67. https://doi.org/10.1016/j.asjsur.2021.06.021 Evertz R, Reinders M, Houck C, Cate Tt, Duijnhouwer AL, Beukema R, Westra S, Vernooy K, de Groot NMS. Atrial fibrillation in patients with an atrial septal defect in a single centre cohort during a long clinical follow-up: its association with closure and outcome of therapy. Open Heart 2020;7(2):e001298. https://doi.org/10.1136/openhrt-2020-001298 Nie JG, Dong JZ, Salim M, Li SN, Wu XY, Chen YW, Bai R, Liu N, Du X, Ma CS. Catheter ablation of atrial fibrillation in patients with atrial septal defect: long-term follow-up results. J Interv Card Electrophysiol 2015;42(1):43-49. https://doi.org/10.1007/s10840-014-9958-z Balk EM, Garlitski AC, Alsheikh-Ali AA, Terasawa T, Chung M, Ip S. Predictors of atrial fibrillation recurrence after radiofrequency catheter ablation: a systematic review. J Cardiovasc Electrophysiol 2010;21(11):1208-1216. https://doi.org/10.1111/j.1540-8167.2010.01798.x Berruezo A, Tamborero D, Mont L, Benito B, Tolosana JM, Sitges M, Vidal B, Arriagada G, Méndez F, Matiello M, Molina I, Brugada J. Pre-procedural predictors of atrial fibrillation recurrence after circumferential pulmonary vein ablation. Eur Heart J 2007;28(7):836-841. https://doi.org/10.1093/eurheartj/ehm027 Mont L, Bisbal F, Hernandez-Madrid A, Perez-Castellano N, Vinolas X, Arenal A, Arribas F, Fernández-Lozano I, Bodegas A, Cobos A, Matía R, Pérez-Villacastín J, Guerra JM, Ávila P, López-Gil M, Castro V, Arana JI, Brugada J; SARA investigators. Catheter ablation vs. antiarrhythmic drug treatment of persistent atrial fibrillation: a multicentre, randomized, controlled trial (SARA study). Eur Heart J 2014;35(8):501-507. https://doi.org/10.1093/eurheartj/eht457 Chen L, Shen J, Shan X, Wang F, Kan T, Tang X, Zhao X, Qin Y. Improvement of tricuspid regurgitation after transcatheter ASD closure in older patients. Herz 2018;43(6):529-534. https://doi.org/10.1007/s00059-017-4594-x Yalonetsky S, Lorber A. Comparative changes of pulmonary artery pressure values and tricuspid valve regurgitation following transcatheter atrial septal defect closure in adults and the elderly. Congenit Heart Dis 2009;4(1):17-20. https://doi.org/10.1111/j.1747-0803.2008.00245.x Tashiro H, Suda K, Iemura M, Teramachi Y. Intergenerational differences in the effects of transcatheter closure of atrial septal defects on cardiac function. J Cardiol 2017;70(6):620-626. https://doi.org/10.1016/j.jjcc.2017.03.014 Additional Declarations No competing interests reported. Supplementary Files Supplementarytable.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4794373","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":341695795,"identity":"f6d5aa60-80a5-4be0-9c05-2f80c53feb0b","order_by":0,"name":"Yuki Matsubara","email":"","orcid":"","institution":"Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yuki","middleName":"","lastName":"Matsubara","suffix":""},{"id":341695796,"identity":"15af2562-c072-4229-9048-78e7b3ae94c4","order_by":1,"name":"Michiyo Yamano","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIiWNgGAWjYDADfvb2gw+ANA8f0Voke84kG4C0sBGtxeBGgpkEiEFQi24Dj+GnGzV35CQbEtIqv+bYybAxMD98dAOPFrMDPMbSOceeGfMzHDx2W3ZbMtBhbMbGOfi1GEjnsB1OnNnYkHZbchszUAsPmzQBLca/c/4dTtxwmMGsWHJbPVFazKRz24BajjGYMX7cdpgILYfZyqxz+w4bS/bwJEszbjvOw8ZMyC/Hmzffzvl2WI5f/vnBjz+3Vdvzszc/fIxPCwMzhwGCzQMm8SkHA/YHcCbjD4KqR8EoGAWjYCQCAKoNR6TPyOwJAAAAAElFTkSuQmCC","orcid":"","institution":"Kyoto Prefectural University of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Michiyo","middleName":"","lastName":"Yamano","suffix":""},{"id":341695797,"identity":"22d30415-33be-4c4f-ac64-892d86e6af86","order_by":2,"name":"Tetsuhiro Yamano","email":"","orcid":"","institution":"Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Tetsuhiro","middleName":"","lastName":"Yamano","suffix":""},{"id":341695798,"identity":"e9bba5ab-7a56-4cbf-8ea3-ff8c9ce3d3f5","order_by":3,"name":"Takeshi Nakamura","email":"","orcid":"","institution":"Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Takeshi","middleName":"","lastName":"Nakamura","suffix":""},{"id":341695799,"identity":"b40f8c17-6382-4384-9be5-8dd8531b9489","order_by":4,"name":"Naohiko Nakanishi","email":"","orcid":"","institution":"Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Naohiko","middleName":"","lastName":"Nakanishi","suffix":""},{"id":341695800,"identity":"4ded876c-6855-4d6c-8ae6-0e4a2e75305b","order_by":5,"name":"Kan Zen","email":"","orcid":"","institution":"Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kan","middleName":"","lastName":"Zen","suffix":""},{"id":341695801,"identity":"c37b49b2-f031-4a01-b33b-5e8854ac4e47","order_by":6,"name":"Hirokazu Shiraishi","email":"","orcid":"","institution":"Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hirokazu","middleName":"","lastName":"Shiraishi","suffix":""},{"id":341695802,"identity":"e6f5d38b-2a23-4c58-ab32-d192f3676eea","order_by":7,"name":"Satoaki Matoba","email":"","orcid":"","institution":"Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Satoaki","middleName":"","lastName":"Matoba","suffix":""}],"badges":[],"createdAt":"2024-07-24 10:01:46","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4794373/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4794373/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63312582,"identity":"0ccd9c5c-9ad3-417d-b204-858582e417bf","added_by":"auto","created_at":"2024-08-26 20:42:25","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":125632,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChanges in right-sided echocardiographic parameters\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData are presented as means ± SD. * p \u0026lt; 0.05 vs. baseline; † p \u0026lt; 0.05 vs. day 2.\u003c/p\u003e\n\u003cp\u003eThe percentage value is the value compared to the baseline value.\u003c/p\u003e\n\u003cp\u003eAF, atrial fibrillation; ASD, atrial septal defect; SR, sinus rhythm; RA, right atrial; RV, right ventricular; TR, tricuspid regurgitation.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4794373/v1/fadf368295a0ce91da2ebb7e.png"},{"id":63313186,"identity":"5d2fd901-805d-46e7-ae2f-7c3dd842c919","added_by":"auto","created_at":"2024-08-26 20:50:25","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":123850,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChange in left-sided echocardiographic parameters\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData are presented as means ± SD. * p \u0026lt; 0.05 vs. baseline; † p \u0026lt; 0.05 vs. day 2.\u003c/p\u003e\n\u003cp\u003eThe percentage value is the value compared to the baseline value.\u003c/p\u003e\n\u003cp\u003eAF, atrial fibrillation; ASD, atrial septal defect; E/e¢, ratio of early diastolic velocity to early diastolic annular velocity; LA, left atrial; LV, left ventricular; MR, mitral regurgitation; SR, sinus rhythm.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4794373/v1/8d88c7fbe78e97885ac2bf44.png"},{"id":63312591,"identity":"45745a5d-446e-46c2-a0f2-c9c994721f90","added_by":"auto","created_at":"2024-08-26 20:42:28","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":390852,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRepresentative cases of cardiac remodeling after atrial septal detect closure in both groups\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMaximum defect size by transesophageal echocardiography is 22.3 mm in a patient in the SR-ASD group (a-1). At baseline, end-diastolic right ventricular (RV) area was 29.6 cm\u003csup\u003e2\u003c/sup\u003e and left atrial (LA) volume index was 37.0 mL/m\u003csup\u003e2\u003c/sup\u003e (a-2). One year later, these values were 15.2 cm\u003csup\u003e2\u003c/sup\u003e and 39.5 mL/m\u003csup\u003e2\u003c/sup\u003e, respectively (a-3).\u003c/p\u003e\n\u003cp\u003eA patient in the AF-ASD group with a maximum defect size of 24.4 mm (b-1). At baseline, end-diastolic RV area was 28.2 cm\u003csup\u003e2\u003c/sup\u003e and LA volume index was 75.8 mL/m\u003csup\u003e2\u003c/sup\u003e (b-2). One year later, these values were 16.3 cm\u003csup\u003e2\u003c/sup\u003e and 105.2 mL/m\u003csup\u003e2\u003c/sup\u003e, respectively (b-3).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4794373/v1/19ee0c8be2b18f8b2bb3c5e5.png"},{"id":63312592,"identity":"9f48011a-fa2b-4cba-ae6c-54d20069d83c","added_by":"auto","created_at":"2024-08-26 20:42:28","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":42439,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChange in New York Heart Association functional classification from baseline to 1 year after the procedure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAF, atrial fibrillation; ASD, atrial septal defect; SR, sinus rhythm.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4794373/v1/39cc46a8921564f5267df0cd.png"},{"id":75091960,"identity":"1b34314c-9b95-4a76-a88f-f0bc01ff6d85","added_by":"auto","created_at":"2025-01-30 11:08:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1684185,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4794373/v1/5cb43719-3bec-49f6-9872-9bfa9aa8a446.pdf"},{"id":63312587,"identity":"a8d153ae-ba84-4a13-9fc5-5e4a6b113d8e","added_by":"auto","created_at":"2024-08-26 20:42:25","extension":"docx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":14629,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarytable.docx","url":"https://assets-eu.researchsquare.com/files/rs-4794373/v1/cb5f1563fbcda5d9d81aa18d.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effects of Transcatheter Atrial Septal Defect Closure in Elderly Patients with Long-Standing Persistent Atrial Fibrillation","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAtrial septal defect (ASD) is one of the most common congenital heart diseases diagnosed in adulthood because many children and young adults have no obvious symptoms [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Transcatheter ASD closure is an effective procedure for most patients with secundum ASD. It is well known that cardiac structural changes and hemodynamic improvement occur immediately after the procedure in both pediatric and adult patients [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, some elderly patients have developed heart failure after the procedure because the increased left ventricular preload after device closure exacerbates underlying left ventricular diastolic dysfunction [\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The incidence of long-standing persistent atrial fibrillation (AF) is increasing with societal aging. These patients are included at a certain rate among patients with ASD [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Few studies have reported cardiac remodeling after transcatheter ASD closure in patients with long-standing persistent AF compared with those in sinus rhythm (SR) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. We aimed to elucidate the structural and hemodynamic changes and clinical outcomes after transcatheter ASD closure in patients with long-standing persistent AF.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eSubjects\u003c/h2\u003e\u003cp\u003eWe enrolled 64 patients aged\u0026thinsp;\u0026gt;\u0026thinsp;70 years out of 253 consecutive patients who underwent transcatheter ASD closure and had successful device implantation at our institution from September 2011 to February 2020. Study participants underwent transthoracic echocardiography (TTE) prior to transcatheter closure and up to 1 year after the procedure. Twelve patients were excluded: three had undergone pulmonary vein isolation for AF, eight could not be followed due to the distance from their home to our institution, and one had died of other diseases. A total of 52 patients (median age, 76 years; 30 women) were included in our study. These patients were divided into two groups: those with long-standing persistent AF (AF-ASD) and those with SR (SR-ASD). All study subjects gave written informed consent.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003eTranscatheter ASD device closure\u003c/h2\u003e\u003cp\u003ePrior to transcatheter closure, all patients underwent transesophageal echocardiography (TEE) to determine the appropriateness of the procedure by assessing all relevant anatomic features such as maximum defect diameter, surrounding rims, and number of defects [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Right heart catheterization was performed to rule out other comorbid structural abnormalities and to measure pulmonary vascular resistance. Transcatheter defect closure was performed under TEE, intracardiac echocardiography, or both TEE and intracardiac echocardiography guidance, as previously reported [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Amplatzer\u0026trade; Septal Occluder (Abbott Medical, Plymouth, MN, USA) or Figulla Flex II ASD Occluder (Occlutech, Jena, Germany) was implanted in 36 and 16 patients, respectively.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eEchocardiographic assessment\u003c/h2\u003e\u003cp\u003eTTE was performed four times: before transcatheter ASD closure, 2 days after closure, 6 months after closure, and 1 year afterward. Comprehensive echocardiograms that included two-dimensional, pulsed-wave, color, and tissue Doppler images were obtained in all patients using a commercially available system (Vivid E9 or Vivid E95; GE HealthCare, Milwaukee, WI, USA). Although the calculation of left atrial (LA) volume in patients undergoing transcatheter ASD closure might have been affected by the area where the implanted device protrudes into the left atrium, the effect varies based on implant shape. Therefore, we avoided the device when we traced the LA border. Left ventricular (LV) end-diastolic diameter, LA volume index, and LV ejection fraction were analyzed for left-sided chambers. For the right-sided chambers, right ventricular (RV) end diastolic area, right atrial (RA) area, and percent fractional area change were assessed [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The severity of atrioventricular valve regurgitation was assessed based on vena contracta width [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The ratio of early diastolic velocity to early diastolic annular velocity (E/e') and tricuspid regurgitation (TR) pressure gradient were used as indices of LV diastolic function and pulmonary hypertension, respectively [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Furthermore, lateral E/e' was used to exclude the direct effect of the implanted ASD device on mitral annular motion [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The authors affirm that human research participants provided informed consent for publication of the images in Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e3\u003c/span\u003ea and \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e3\u003c/span\u003eb.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eAssessment of heart failure\u003c/h2\u003e\u003cp\u003eNew York Heart Association (NYHA) functional classification and plasma brain natriuretic peptide (BNP) levels were assessed at baseline and 1 year after the procedure. Plasma BNP levels were measured using a specific immunoradiometric assay (architect BNP-JP, Abbott Japan, Tokyo, Japan).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eAll normally distributed values are expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Non-normally distributed values are expressed as medians and interquartile range. The chi-squared test was performed for categorical variables. Repeated measures analysis of variance followed by post hoc analysis was used for continuous variables. A two-tailed p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. The percentage of values at each time point compared to baseline was calculated and compared between the two groups using the unpaired t-test. All statistical analyses were performed using JMP software (version 16, SAS Institute Inc, Cary, NC, USA).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003ePatient characteristics and baseline echocardiographic parameters\u003c/h2\u003e\u003cp\u003eAlthough there were no significant differences in age, the incidence of symptomatic heart failure and proportion of patients prescribed diuretics were significantly higher in the AF-ASD group than in the SR-ASD group (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Mean pulmonary artery pressure was significantly higher in patients with AF-ASD. Baseline echocardiographic parameters are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Although right-sided chambers and LA volume were significantly larger in patients with AF-ASD, biventricular systolic function did not differ between the two groups. The difference of severity in MR and TR were statistically significant. All the etiologies of atrioventricular valve regurgitation equal or more than moderate degree were annular dilatation.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline Characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAF-ASD\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSR-ASD\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e78 .5 [74.0\u0026ndash;82.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e74.5 [71.8\u0026ndash;80.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.207\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (59%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (57%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.908\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBody surface area, m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.578\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNYHA functional classification\u0026thinsp;\u0026ge;\u0026thinsp;2, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (100%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (57%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (53%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15 (43%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.494\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDyslipidemia, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (29%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15 (43%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.345\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCoronary artery disease, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.980\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (18%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (11%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.670\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (12%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.591\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalcium antagonist, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (35%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (31%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.780\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBeta-blocker, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (35%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (11%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.041\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eACE-I/ARB, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (35%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (23%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.343\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiuretic, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (76%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (23%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiac catheterization data\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eQp/Qs\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.2 [1.8\u0026ndash;3.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.5 [2.0\u0026ndash;2.8]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.904\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePVR, Wood units\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.5 [1.5\u0026ndash;2.7]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.6 [1.3\u0026ndash;2.1]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.024\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean PAP, mmHg\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30 [\u003cspan additionalcitationids=\"CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32 CR33 CR34 CR35 CR36 CR37\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 [\u003cspan additionalcitationids=\"CR18 CR19 CR20 CR21 CR22\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaximum ASD size on TEE, mm\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18.5 [13.3\u0026ndash;20.8]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17.0 [14.4\u0026ndash;20.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.984\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDevice size, mm\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20.0 [16.3\u0026ndash;25.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21.0 [18.0\u0026ndash;24.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.687\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003e*\u003c/sup\u003eValues are medians [interquartile range].\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eACE-I, angiotensin-converting enzyme inhibitor; AF, atrial fibrillation; ARB, angiotensin receptor blocker; ASD, atrial septal defect; NYHA, New York Heart Association; PAP, pulmonary arterial pressure; PVR, pulmonary vascular resistance; Qp/Qs, ratio of pulmonary blood flow to systemic blood flow; SR, sinus rhythm; TEE, transesophageal echocardiography.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline Transthoracic Echocardiographic Parameters\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAF-ASD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSR-ASD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRV end diastolic area, cm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e30.5\u0026thinsp;\u0026plusmn;\u0026thinsp;7.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e25.4\u0026thinsp;\u0026plusmn;\u0026thinsp;7.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.046\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRV fraction area change, %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e39.9\u0026thinsp;\u0026plusmn;\u0026thinsp;9.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e41.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.790\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRA area, cm\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e32.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e21.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTR pressure gradient, mmHg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e35.5\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e31.7\u0026thinsp;\u0026plusmn;\u0026thinsp;12.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.148\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLV end diastolic diameter, mm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e40.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e37.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.087\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLV ejection fraction, %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e62.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e64.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.201\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLA volume index, mL/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e66.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e43.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eE, m/s\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e0.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e0.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eE/e\u0026lsquo;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e14.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e11.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.011\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTR vena contracta width, mm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e5.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.027\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMR vena contracta width, mm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003e*\u003c/sup\u003eValues are presented as mean\u0026thinsp;+\u0026thinsp;SD.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eAF, atrial fibrillation; ASD, atrial septal defect; E, early diastolic velocity; E/e\u0026prime;, ratio of E to early diastolic annular velocity; LA, left atrial; LV, left ventricular; MR, mitral regurgitation; RA, right atrial; RV, right ventricular; SR, sinus rhythm; TR, tricuspid regurgitation.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003eRemodeling after transcatheter ASD closure\u003c/h2\u003e\u003cp\u003eLongitudinal changes in the parameters assessed with TTE from baseline to 1 year after the procedure are shown in Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e. With respect to the right-sided chambers, significant reverse remodeling began immediately after the procedure and continued in both groups up to 1 year after the procedure (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The percentage values of RV and RA areas were not significantly different between patients with AF-ASD and SR-ASD. RV fractional area change did not change significantly over time in the either group. TR pressure gradient decreased significantly in both groups immediately after the procedure; percentage value at 1 year was comparable between the two groups. TR vena contracta width showed comparable improvement in the two groups. The increase in LA volume and LV end-diastolic diameter persisted up to 1 year after the procedure in both groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In addition, the percentage value of LA volume index was significantly different between the two groups during the follow-up period. The percentage value of LV ejection fraction did not differ between the two groups over time. There were no significant changes in E/e' over the 1-year follow-up period in either group, but there was a transient increase in the SR-ASD group at 2 days after the procedure. Changes in mitral regurgitation vena contracta width at 6 months and 1 year were statistically significant in both groups; these changes were comparable between the two groups. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows representative cases in both groups with a comparable maximum defect size. Although reductions in right-sided chamber parameters were similar in both patients, LA enlargement was more pronounced in a patient with AF-ASD.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eHeart failure after transcatheter ASD closure\u003c/h2\u003e\u003cp\u003eImprovement in NYHA functional classification was seen in almost all symptomatic patients in both groups, except for one patient in the AF-ASD group (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). There were no significant changes in plasma BNP levels over time in patients with SR-ASD (median [interquartile range], 61.6 pg/mL [37.3\u0026ndash;99.8] at baseline to 62.6 pg/mL [35.3\u0026ndash;93.8] at 1 year, p\u0026thinsp;=\u0026thinsp;0.371). In contrast, patients with AF-ASD had a significant decrease after ASD closure (336.2 pg/mL [145.1\u0026ndash;491.4] to 173.8 pg/mL [73.6\u0026ndash;261.7], p\u0026thinsp;=\u0026thinsp;0.032). Two patients with AF-ASD were hospitalized for decompensated heart failure during the follow-up period.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe investigated the cardiac chamber remodeling process after transcatheter ASD closure in elderly patients with long-standing persistent AF compared with those in SR. Although remodeling of the right-sided chambers and TR improvement were observed in patients with AF-ASD as well as in those with SR-ASD, LA enlargement was prominent only in patients with AF-ASD. Symptoms of heart failure lessened and plasma BNP levels decreased in patients with AF-ASD at 1 year after the procedure.\u003c/p\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eRemodeling of cardiac chambers\u003c/h2\u003e\u003cp\u003eChronic volume overload of the right-sided chambers caused by the existence of ASD leads to RV enlargement, RV dysfunction, and might eventually cause chronic heart failure. In addition, chronic RV volume overload in patients with ASD has been reported to cause LV systolic and diastolic dysfunction due to multiple complex factors such as worsening ventricular interdependence [\u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Thus, restoration of right-to-left volume balance is the expected goal of ASD closure. Transcatheter ASD closure produces early and pronounced cardiac structural changes that almost completely restore the volume balance between the right and left cardiac chambers [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], i.e., the right heart shrinks and the left heart expands. Remodeling of cardiac chambers began immediately after the procedure and changes continued for 6 months or 1 year after the procedure, but the rate of the process slowed [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The sizes of the right-sided chambers at 1 year follow-up compared to normal controls differ depending on the published report [\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Although a reduction in RV size has been reported in all age groups, the degree of reduction was smaller in elderly patients [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Although the changes in ventricular size 2 days after the procedure were not statistically significant except for RV end-diastolic area in SR-ASD, remodeling was observed up to 1 year after the procedure in both our AF-ASD and SR-ASD patients.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eASD closure for elderly patients\u003c/h2\u003e\u003cp\u003eTranscatheter ASD closure is considered an effective alternative to surgery even in elderly patients with multiple comorbidities due to its low complication rate and short hospital stay [\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. However, heart failure due to elevated LV filling pressure after transcatheter ASD closure should be considered a complication unique to elderly patients [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Although the left ventricle is unloaded by interatrial shunt flow and the increase in LV filling pressure is masked before closure in patients with LV diastolic dysfunction, it might become clinically evident after the procedure [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. We assessed LV filling pressure prior to the procedure to after the procedure by lateral E/e\u0026rsquo;. Lateral E/e\u0026rsquo; increased 2 days after the procedure in patients with SR-ASD, whereas the changes in the value in patients with AF-ASD during the follow-up period were not statistically significant (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Its change was consistent with the change in plasma BNP level in patients with SR-ASD, though the changes from before the procedure to 1 year after the procedure were not statistically significant (Supplementary Table\u0026nbsp;1). Preprocedural assessment of high-risk patients is important and early initiation of anti-congestive conditioning therapy might be useful [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The number of elderly patients who experience heart failure after the procedure is limited; most patients experience a decrease in their symptoms [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Exercise capacity, usually assessed based on NYHA functional classification or maximal oxygen consumption, improved after transcatheter ASD closure even in patients with no or mild symptoms [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Prochownik et al. [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] reported changes in symptoms from prior to the procedure up to 1 year after the procedure in adult patients. The number of symptomatic patients decreased at 1 month after the procedure and continued to decrease up to 1 year after the procedure. Maximal oxygen consumption increased significantly from baseline to 1 year after the procedure, but the degree of improvement was lower in patients aged\u0026thinsp;\u0026gt;\u0026thinsp;40 years than in those aged\u0026thinsp;\u0026le;\u0026thinsp;40 years. Some authors have reported the efficacy of transcatheter ASD closure in patients with an average age greater than 65 years [\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. All of these studies showed significant improvements in physical activity observed approximately 1 year after the procedure compared to baseline, even though the method of assessment differed depending on the study: 6-minute walk test, cardiopulmonary exercise test, or NYHA functional classification. Improvement in mental scores after the procedure has also been reported in elderly patients [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eTranscatheter ASD closure in elderly patients with long-standing persistent AF\u003c/h2\u003e\u003cp\u003eCompared with age- and gender-matched controls, patients with ASD have a higher incidence of AF, whether or not closure is performed [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Furthermore, the incidence increases with age both before and after the intervention [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Although the advisability of catheter-based treatment for AF prior to ASD closure has often been discussed [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], the consensus opinion on how to proceed or the background of optimal candidates for catheter ablation in ASD patients with AF has not been published [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. In addition, the choice of catheter ablation before transcatheter ASD closure is not always recommended for patients with long duration of AF or prominent left atrial enlargement who are unlikely to benefit from catheter intervention [\u003cspan additionalcitationids=\"CR39\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. The efficacy of transcatheter ASD closure in patients with long-standing persistent AF without intervention for arrhythmia has rarely been reported. Taniguchi et al. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] reported outcomes after transcatheter ASD closure in elderly patients with long-standing persistent AF. Nine patients who underwent transcatheter ASD closure were followed from before the procedure to more than 6 months after the procedure. RV remodeling, assessed based the ratio of RV to LV diameter, improved. NYHA functional classification and plasma BNP levels improved. Another study analyzed chamber remodeling in patients with long-standing persistent AF before and 6 months after the procedure compared to patients in SR [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Patients with AF had a smaller degree of change in right-sided chambers than patients in SR, whereas symptom relief was comparable in both groups during the follow-up period. The patients with AF in their study were significantly older than those in SR (mean age, 68.3\u0026thinsp;\u0026plusmn;\u0026thinsp;15.4 vs. 47.4\u0026thinsp;\u0026plusmn;\u0026thinsp;13.9 years), so the effect of age on the remodeling process cannot be excluded [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. As in these previous studies, right heart remodeling and relief of heart failure symptoms in our study were also achieved in patients with AF-ASD and were comparable to those with SR-ASD of the same age. The improvement in TR and TR pressure gradient is also favorable, as reported previously [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Although LA volume of patients with AF in our study increased after the procedure, the remodeling of the left atrium after transcatheter ASD closure in elderly patients differs across studies [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. This might be due to the fact that most studies partially included patients with AF and the number of studies focusing on patients with AF is limited [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Although LA remodeling might occur after the procedure, transcatheter ASD closure is a useful and acceptable treatment for heart failure in patients who have difficulty maintaining SR.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eLimitations\u003c/h2\u003e\u003cp\u003eThis study has some limitations. First, this is a retrospective, single-center study with a small number of patients. Further study with a large number of patients is needed. Second, we only estimated the severity of atrioventricular valve regurgitation using a semi-quantitative method. Atrioventricular valve regurgitation was mild, especially mitral regurgitation in the SR-ASD group, so it was difficult to compare severity based on a quantitative method. Finally, we used two-dimensional echocardiographic parameters to assess the right ventricle, which has a complex geometry. However, we used the chamber quantification methods recommended in the guidelines [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eTranscatheter ASD closure is an effective treatment for heart failure in elderly ASD patients with long-standing persistent AF in terms of reversal of right heart remodeling and lessening of heart failure symptoms.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAF, atrial fibrillation\u003c/p\u003e\n\u003cp\u003eASD, atrial septal defect\u003c/p\u003e\n\u003cp\u003eBNP, brain natriuretic peptide\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eE/e\u0026cent;, ratio of early diastolic velocity to early diastolic annular velocity\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLA, left atrial\u003c/p\u003e\n\u003cp\u003eLV, left ventricular\u003c/p\u003e\n\u003cp\u003eNYHA,\u0026nbsp;New York Heart Association\u003c/p\u003e\n\u003cp\u003eRA, right atrial\u003c/p\u003e\n\u003cp\u003eRV, right ventricular\u003c/p\u003e\n\u003cp\u003eSR, sinus rhythm\u003c/p\u003e\n\u003cp\u003eTEE, transesophageal echocardiography\u003c/p\u003e\n\u003cp\u003eTR, tricuspid regurgitation\u003c/p\u003e\n\u003cp\u003eTTE, transthoracic echocardiography\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki, as reflected in the prior approval by the ethics committee of Kyoto Prefectural University of Medicine (ERB-C-835-4).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eYuki Matsubara: Conceptualization, Methodology, Formal analysis, Investigation, and Writing-Original Draft. Michiyo Yamano: Conceptualization, Methodology, Formal analysis, Investigation, Writing-Original Draft, Writing-Review and Editing, Visualization, Supervision, and Project administration. Tetsuhiro Yamano: Resources and Writing-Review and Editing. Takeshi Nakamura: Resources, Data Curation, and Writing-Review and Editing. Naohiko Nakanishi: Resources and Writing-Review and Editing. Kan Zen: Resources and Writing-Review and Editing. Hirokazu Shiraishi: Resources and Writing-Review and Editing. Satoaki Matoba: Resources, Writing-Review and Editing, and Supervision.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eNone\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLindsey JB, Hillis LD. Clinical update: atrial septal defect in adults. Lancet 2007;369(9569):1244-1246. https://doi.org/10.1016/S0140-6736(07)60576-5\u003c/li\u003e\n\u003cli\u003eSamanek M, Slavik Z, Zborilova B, Hrobonova V, Voriskova M, Skovranek J. 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J Cardiol 2017;70(6):620-626. https://doi.org/10.1016/j.jjcc.2017.03.014\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"atrial septal defect, atrial fibrillation, elderly patients, heart failure","lastPublishedDoi":"10.21203/rs.3.rs-4794373/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4794373/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eAlthough the safety and efficacy of transcatheter atrial septal defect (ASD) closure has been reported in elderly patients, postprocedural outcomes in elderly patients with long-standing persistent atrial fibrillation (AF) have not been fully assessed. The aim of this study was to elucidate the cardiac remodeling process and symptom improvement after transcatheter ASD closure in elderly patients with AF (AF-ASD) compared to those in sinus rhythm (SR-ASD). \u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe enrolled 52 patients aged\u0026thinsp;\u0026gt;\u0026thinsp;70 years out of 253 consecutive patients who underwent transcatheter ASD closure. We retrospectively analyzed serial echocardiograms, New York Heart Association (NYHA) functional classification, and plasma brain natriuretic peptide (BNP) levels from baseline to 1 year after the procedure.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eWith respect to the right-sided chambers, significant reverse remodeling began immediately after the procedure and continued in both groups up to 1 year after the procedure. Left ventricular augmentation was comparable in both groups. Left atrial volume increase was prominent in the AF-ASD group, with a statistically significant difference compared with the SR-ASD group from 2 days to 1 year after the procedure (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). NYHA functional classification improved in both groups. Plasma BNP levels decreased only in the AF-ASD group from baseline to 1 year (median value [interquartile range], 336.2 pg/mL [145.1\u0026ndash;491.4] to 173.8 pg/mL [73.6\u0026ndash;261.7], p\u0026thinsp;=\u0026thinsp;0.032).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eTranscatheter ASD closure is an effective treatment for heart failure in elderly patients with ASD and long-standing persistent AF.\u003c/p\u003e","manuscriptTitle":"Effects of Transcatheter Atrial Septal Defect Closure in Elderly Patients with Long-Standing Persistent Atrial Fibrillation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-26 20:42:19","doi":"10.21203/rs.3.rs-4794373/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"214e5e82-8972-4804-887b-662546c6c29f","owner":[],"postedDate":"August 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-30T11:08:16+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-26 20:42:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4794373","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4794373","identity":"rs-4794373","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}