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Congenital heart disease
Original research article
Atrial septal defect closure in adulthood is associated with normal survival in the mid to longer term
  1. Margarita Brida1,2,3,
  2. Gerhard-Paul Diller1,2,4,
  3. Aleksander Kempny1,
  4. Maria Drakopoulou1,
  5. Darryl Shore1,
  6. Michael A Gatzoulis1,2,
  7. Anselm Uebing1,5
  1. 1 Adult Congenital Heart Centre and Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK
  2. 2 National Heart and Lung Institute, Imperial College London, London, UK
  3. 3 Division of Adult Congenital Heart Disease, Department of Cardiovascular Disease, University Hospital Centre Zagreb, Zagreb, Croatia
  4. 4 Division of Adult Congenital and Valvular Heart Disease, Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany
  5. 5 Division of Paediatric Cardiology, University Hospital Muenster, Muenster, Germany
  1. Correspondence to Dr Margarita Brida, Adult Congenital Heart Centre and Centre for Pulmonary Hypertension, Royal Brompton Hospital, London SW3 6NP, UK; margarita.brida{at}icloud.com

Abstract

Objective The prognostic benefit of atrial septal defect (ASD) closure in adulthood, particularly in advanced age, remains uncertain. The aim of our study was to examine the impact of ASD closure in a contemporary adult cohort on mid to longer term survival as compared with expected survival in the general population.

Methods We study herewith all consecutive patients (≥16 years of age) who underwent ASD closure, catheter or surgical, at our tertiary centre between 2001 and 2012. Furthermore, we compare survival of our ASD closure cohort with expected survival in age and gender-matched general population and standardised mortality ratios (SMR) were calculated.

Results A total of 608 patients (mean age 45.4±16.7 years) underwent ASD closure (catheter 433(71.2%), surgical 175(28.8%)). There was no 30-day mortality and periprocedural complications were low (n=40, 6.6%). During a median follow-up of 6.7 (IQR 4.2–9.3) years 16 (2.6%) patients died; survival was similar to the general population (p=0.80) including patients >40 or >60 years of age at ASD closure (p=0.58 and p=0.64, respectively). There was no survival difference between gender (male: SMR 0.93; 95% CI 0.52 to 1.64, p=0.76; female: SMR 0.99; 95% CI 0.58 to 1.66, p=0.95) or mode of closure compared with general population (catheter: SMR 1.03; 95% CI 0.68 to 1.55, p=0.89; surgical: SMR 0.65; 95% CI 0.22 to 1.88, p=0.38).

Conclusion Perioperative mortality and morbidity in a large contemporary adult cohort undergoing ASD closure, catheter or surgical, is extremely low. Mid to longer term survival is excellent irrespective of age, gender and mode of closure, and similar to matched general population.

  • atrial septal defect
  • survival
  • catheter ASD closure
  • surgical ASD closure

http://dx.doi.org/10.1136/heartjnl-2018-314380

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    Introduction

    Atrial septal defect (ASD) is the most common congenital heart defect diagnosed in adulthood accounting for 25%–30% of new diagnoses.1 A distinct feature of ASD accounting for late diagnosis is its slow clinical progression, usually not leading to debilitating symptoms, until or after the fourth or fifth decade of life.2 Despite being considered a ‘simple’ defect, if untreated, ASD is associated with significant late morbidity and mortality.3 This has resulted to a more proactive approach, whereas once an ASD is diagnosed in adulthood, patients with evidence of right ventricle (RV) overload are advised to ASD closure irrespective of symptoms, provided that significant pulmonary arterial hypertension is not present.4 Secundum-type ASDs can often be closed percutaneously, whereas primum and sinus venosus defects require surgical closure.5 Early closure during childhood, adolescence and early adulthood has been shown to convey excellent long-term results with normal survival.6 7 Uncertainty, however, exists regarding the survival benefits of ASD closure in adulthood, particularly in advanced age. There are conflicting data, suggesting that surgical ASD closure after the age of 40 may have increased late mortality compared with healthy, matched controls,7 8 whereas others have suggested both symptomatic and survival benefits even when ASD closure takes place after the age of 40.9 10 Moreover, there is scarcity of data on long-term survival of patients undergoing catheter closure.11–14 Finally, the most recent cohort study based on a Danish national registry indicated higher mortality among patients with ASD in comparison to the general population over a follow-up of 18 years.15

    The aim of our study was to determine contemporary mid to longer term survival of adult patients after catheter or surgical closure of ASD at a high-volume single tertiary centre practising a proactive approach towards closure. Furthermore, we examined the relation of age, gender, type of ASD and mode of closure on outcome and compared survival after closure with age and gender-matched general population survival data from the UK.

    Methods

    Study patients

    We retrospectively enrolled all consecutive patients (≥16 years of age) who underwent catheter or surgical closure of ostium secundum or sinus venosus ASD at a single tertiary centre (Royal Brompton Hospital, London, UK) between January 2001 and December 2012. As this was a retrospective analysis based on data collected for routine clinical care and administrative purposes (UK National Research Ethics Service guidance), individual informed consent was not required.

    Patients’ data including age, gender, type and size of ASD, comorbidities, New York Heart Association (NYHA) functional class, right ventricular systolic pressure and right ventricular size were obtained from medical records. Patients with comorbidities such as previous myocardial infarction, diabetes mellitus, arterial hypertension and dyslipidaemia were included in the study. Exclusion criteria were concomitant cardiac structural abnormalities, partial atrioventricular septal defect (because of important additional pathology such as left atrioventricular valve abnormality and predisposition to heart block) and established pulmonary vascular disease.

    Indication for closure was significant left-to-right shunt via an unrestricted ASD with evidence of right ventricular volume overload irrespective of the presence of symptoms. The postprocedural mid to longer term survival was compared with that of an age and gender-matched population of England and Wales. Data on overall mortality were retrieved from the Office for National Statistics, which registers all UK deaths. The cause of death was established from medical records and death certificates, available for all patients.

    Echocardiography

    A comprehensive transthoracic echocardiographic study was performed in all patients before ASD closure. Right ventricular systolic pressure was measured from tricuspid regurgitation peak Doppler gradient and used to estimate systolic pulmonary arterial pressure. Quantitative measures on RV size measured from 2D and M-mode echocardiography were taken into consideration to grade ventricular size as normal, mildly, moderately or severely dilated.16

    Right heart catheterisation

    Right heart catheterisation was performed prior to ASD closure in selected patients when echocardiography finding where either non-conclusive (inadequate Doppler trace), suggested systolic pulmonary arterial pressure more than 50% of systemic, or when absolute values were more than 60 mm Hg. Pulmonary vascular resistance (PVR) was assessed in all patients studied. Patients remained candidates for ASD closure when PVR index is ≤4 Wood units×m2 with no evidence of resting or exercise-induced desaturation.

    Catheter ASD closure

    All catheter ASD closures were performed under general anaesthesia with endotracheal intubation, guided by fluoroscopy and transoesophageal echocardiography. The type of the device implanted, fluoroscopy time, total procedural time, length of hospital stay and periprocedural complications were recorded in all patients. Patients received antiplatelet therapy for 6 months after ASD catheter closure and were advised to receive antibiotic prophylaxis for endocarditis during this period.

    Surgical ASD closure

    Patients with secundum ASD not suitable for catheter closure (very large ASD or ASD with inadequate septal rims) and patients with sinus venosus ASD underwent surgical repair under cardiopulmonary bypass. Bypass time, cross-clamp time, length of hospital stay and periprocedural complications were recorded in all patients.

    Statistical analysis

    Data are presented as mean±SD or median and IQR for continuous variables, while categorical variables are presented as numbers (percentages). Comparison between groups was performed for continuous variables using Mann-Whitney test, while distribution of categorical variables was assessed using Χ2 test. To estimate standardised mortality ratios (SMR) compared with an age and gender-matched sample of the general UK population, the method reported by Finkelstein et al was used.17 Survival was compared with that predicted for an age and gender-matched healthy cohort of UK residents using life table data (2007–2009 interim life tables) published by the Government Actuary’s Department (http://www.gad.gov.uk).17 Differences in survival were assessed using log-rank test. Statistical analyses were performed using R package V.3.0.218 A two-sided p value <0.05 was considered indicative of statistical significance.

    Results

    Baseline characteristics

    A total of 608 consecutive patients who underwent ASD closure at a mean age of 45.4±16.7 (range 16–92) years (female 388, 63.8%) were enrolled in the study. Patients were followed for a median of 6.7 (IQR 4.2–9.3) years. The majority of patients had an ostium secundum ASD (552, 90.8%), the remainder a sinus venosus ASD (56, 9.2%). The mean defect size was 22.3±8.8 mm. Comorbidity conditions were relatively uncommon and included systemic hypertension (9.0%), dyslipidaemia (8.1%), prior stroke (4.8%), ischaemic heart disease (4.4%) and diabetes mellitus (2.8%). Previous arrhythmia was evident in approximately a fifth of patients (atrial fibrillation in 14.5%, atrial flutter in 4.4%). The majority of patients were asymptomatic in NYHA functional class I (401, 66.0%); 32.2% of patients were mildly symptomatic NYHA functional class II, with only 1.8% in class III. Four hundred and thirty-three (71.2%) patients had catheter ASD closure; the remainder had 175 (28.8%) surgical closure. There was no in-hospital or early (30-day) mortality. Baseline demographics and clinical characteristics are summarised in table 1.

    View this table:
    Table 1

    Patient demographics and clinical characteristics

    Catheter versus surgical ASD closure

    The majority of patients with a secundum-type ASD underwent catheter closure (catheter 78.4% vs surgical 21.6%), which represents the treatment of choice. Patients undergoing catheter ASD closure were older than patients undergoing surgery (46.7±17.2 vs 42.1±15.0 years, p<0.01). As expected, the length of hospital stay was significantly shorter in the ASD catheter closure subgroup. Discharge from hospital was at a median of 1 (IQR 1–1) day after catheter closure and a median of 6 (IQR 5–9) days after surgical closure. Procedural time for the catheter closure group and bypass and cross-clamp times for the surgical group are given in table 1. The Amplatzer Septal Occluder device was used in the vast majority of 398 (91.9%) patients undergoing catheter closure. There were overall 40 (6.6%) cases of periprocedural complications (4.6% for catheter and 11.4% for surgical closure); arrhythmia was the most common among them (19, 3.1%) (table 2).

    View this table:
    Table 2

    Periprocedural complications

    Follow-up

    There was no in-hospital or early (30-day) mortality in our study. During a median follow-up of 6.7 (IQR 4.2–9.3) years 16 patients died. Cause of death was in majority malignant disease (7) or pneumonia and/or sepsis (5), followed by coronary artery disease (1), cerebral haemorrhage (1), trauma injury (1) and chronic heart failure (1). There was no significant difference in mortality between the ASD cohort in comparison to the expected mortality in an age and gender-matched UK population, SMR 0.96 (95% CI 0.65 to 1.41; p=0.80) (figure 1). Interestingly, survival of patients who underwent ASD closure aged older than 40 years, and even older than 60 years, was similar to the expected mortality in matched population with SMR 0.90 (95% CI 0.60 to 1.36; p=0.58) and SMR 0.91 (95% CI 0.58 to 1.43; p=0.64), respectively (figure 2). Moreover, survival patterns did not differ when mode of closure was examined separately; survival after catheter SMR 1.03 (95% CI 0.68 to 1.55; p=0.89) or surgical closure SMR 0.65 (95% CI 0.22 to 1.88; p=0.38) was not different compared with the reference general population (figure 3). The same was true when gender was analysed separately; there was no difference in relative survival between male patients (SMR 0.93 (95% CI 0.52 to 1.64; p=0.76)) or female patients (SMR 0.99 (95% CI 0.58 to 1.66; p=0.95)) compared with the general population (figure 4).

    Figure 1
    Figure 1

    Survival of 608 adult patients after ASD closure compared with age and gender-matched general population. No differences during a median follow-up of 6.7 years were observed. Dashed lines represent 95% CIs. P values refer to differences between groups. ASD, atrial septal defect; SMR, standardised mortality ratio.

    Figure 2
    Figure 2

    Survival of patients older than 40 or 60 years of age at the time of ASD closure compared with age and gender-matched general population. No differences during follow-up were observed. Dashed lines represent the 95% CIs. P values refer to differences between groups. ASD, atrial septal defect; SMR, standardised mortality ratio.

    Figure 3
    Figure 3

    Survival of patients after catheter or surgical ASD closure compared with age and gender-matched general population. No differences in survival during follow-up were observed. Dashed lines represent 95% CIs. P values refer to differences between groups. ASD, atrial septal defect; SMR, standardised mortality ratio.

    Figure 4
    Figure 4

    Survival after ASD closure in male and female patients compared with age and gender-matched general population. No differences were observed. Dashed lines represent 95% CIs. P values refer to differences between groups. ASD, atrial septal defect; SMR, standardised mortality ratio.

    Freedom from cardiovascular events (stroke, pulmonary embolism, atrioventricular heart block with need for pacemaker implantation, pulmonary vascular disease) after 6 weeks, 1, 5 and 10 years was 97.9%, 96.7%, 89.1% and 73.2%, respectively. Freedom from new-onset atrial tachyarrhythmia in the subgroup of patients with no history of atrial arrhythmia prior to ASD closure was 98.1%, 96.7%, 88.6% and 77.3% at 6 weeks, 1, 5 and 10 years, respectively (figure 5). There were no differences in freedom from cardiovascular events and new-onset atrial tachyarrhythmia between the catheter and surgical ASD closure subgroups (log-rank p=0.22 and p=0.53, respectively).

    Figure 5
    Figure 5

    Freedom from cardiovascular events (A) and atrial tachyarrhythmia (B) after atrial septal defect (ASD) closure in adulthood. (A) Freedom from cardiovascular events (stroke, pulmonary embolism, atrioventricular heart block with need for pacemaker implantation and pulmonary vascular disease) after ASD closure. (B) Freedom from atrial tachyarrhythmia after ASD closure among patients who were in sinus rhythm at the time of closure.

    Discussion

    Our data show no perioperative mortality and low periprocedural morbidity in a large, contemporary, single tertiary centre adult cohort undergoing ASD closure, catheter or surgical, between 2001 and 2012. Patients received a proactive approach and advice to ASD closure in the presence of right heart dilatation and a non-restricted ASD. Indeed, all patients had right heart dilatation with the majority being asymptomatic or mildly symptomatic at the time of the closure. Over a median follow-up of 6.7 years survival was excellent irrespective of age at the time of ASD closure, gender and mode of ASD closure, and not different from the expected survival in a matched UK general population.

    ASD closure and survival

    While overall reduction in morbidity and consequently improvement in quality of life has been shown after closure of ASD irrespective of age,19–21 life expectancy of patients with ASD closure in adulthood is nevertheless considered to be impaired when compared with healthy controls.15 Our contemporary data show that a proactive ASD closure approach in adulthood is associated with normal survival compared with that expected in the general population matched for gender and age in the mid to longer term follow-up. This novel and important finding from our study was independent of age at the time of closure, gender and mode of ASD closure. Several reasons may account for this, including better patient selection in a tertiary centre, excluding, for example, patients with important pulmonary hypertension4 22 and/or patients with left ventricular disease. Awareness that ASD closure in patients with pulmonary arterial hypertension carries a poor prognosis23 has led to more thorough evaluation of borderline patients within the ‘grey area’ for pulmonary vascular disease (when PVR index is between 4 and 8 Wood units×m2).4 22 We submit, however, that the excellent outcome reported herewith largely reflects our proactive approach of offering ASD closure mainly for prognostic reasons before cardiac decompensation and overt symptoms ensue. This contrasts to historical studies of pioneering era of cardiac surgery7 and reports of registries span over a long period of intervention with a different and more ‘reactive’ approach and also longer periods of follow-up, both relevant to the different outcomes reported in these studies, compared with the present study.15 We have clearly come a long way in ASD closure. We have better myocardial protection (surface vs deep hypothermia) and shorter cardiopulmonary bypass and cross-clamp time for surgical ASD closure. Equally important has been the introduction and establishment of catheter device closure as the treatment of choice for most patients with secundum ASD, thus avoiding sternotomy and cardiac ischaemia altogether. These advances, in turn, minimise myocardial injury and ameliorate right ventricular remodelling, as recently demonstrated even in elderly patients after catheter closure.19 Finally, follow-up care has improved, especially in tertiary centres such as ours, with better awareness, timely detection and prompt therapy of complications following ASD closure in adulthood. Arrhythmias, for example, whether pre-existing or new onset after ASD closure, are relatively common, especially in older patients.24 Preoperative, intraoperative or postoperative arrhythmia targeting interventions (catheter or surgical ablation), thromboprophylaxis to prevent stroke and thrombosis (in the current era also with non-vitamin K antagonist anticoagulation drugs) and antiarrhythmic drug therapy are all part of routine care leading to improved superior outcomes compared with earlier reports of ASD closure in adulthood.

    All in all, we submit that earlier diagnosis and timely management of adults with ASD, before clinical decompensation ensues, meticulous patient selection for those in the grey area at tertiary centres and improved therapies have all contributed to the excellent mid to longer term survival reported herewith. Furthermore, there were no periprocedural deaths in our 608 consecutive patients, whether catheter or surgical, which reinforces that ASD closure is a very safe procedure with also low rate of complications.

    Mode of ASD closure and gender

    More than two-thirds of our patients underwent catheter closure of ASD, reflective of contemporary practice. They had, as expected, much shorter hospital stay and lower rates of periprocedural complications compared with the more invasive nature of surgical ASD closure. Survival outcomes were, however, similar between catheter and surgical ASD closure subgroups compared with age and gender-matched general population (figure 3). Furthermore, we show no gender effect on survival in our study, which is in contrast to a study published from a Dutch registry where male gender was associated with worse survival than a gender-matched general population.25 Whether social or other risk factors are contributory, or differences in healthcare systems may be in part responsible for this discrepancy is speculative. Our data are reassuring, and we cannot ascertain reasons for worse survival among male patients with ASD versus female counterparts given their relatively young age and no differences in their baseline characteristics (figure 4).

    Cardiovascular complications and arrhythmia after ASD closure

    Freedom from cardiovascular complications at 5 and 10 years after ASD closure was 89% and 73%, respectively, with similar rates of new-onset atrial tachyarrhythmia among patients who were in sinus rhythm at the time of closure (figure 5). Interestingly, occurrence of new-onset arrhythmia after ASD closure was similar between catheter and surgical groups. This suggests that chronic right atrial (and pulmonary venous) dilatation and stretch rather than surgical scars are the main pathophysiologic substrate for arrhythmia genesis in our contemporary cohort. Our finding of ongoing cardiovascular morbidity during follow-up despite successful ASD closure in adulthood reinforces the need for timely closure when the diagnosis is made; to achieve maximum right heart reverse remodelling that is age dependent. Furthermore, it underscores the need for long-term follow-up, especially among older patients to identify and timely manage late complications.26

    Study limitations

    Our study is limited by its retrospective design. Furthermore, the length of follow-up was relatively modest. Previously shown incomplete reverse right ventricular/right atrial remodelling in older patients with ASD26 may have a negative impact on survival in the longer term in our cohort. Moreover, we cannot exclude the possibility that late complications, such as arrhythmia, may have been underestimated in the study. The majority of our patients, however, remain under periodic follow-up. We also operate a policy whereas patients are encouraged to contact and inform us of any concerns or complications if and when they may arise.

    Comparing survival of our adult patients with ASD after closure with an age and gender-matched general population from England and Wales was also a relative weakness of our study. However, randomising patients with ASD to a closure group versus following natural history of living with an ASD would not be in line with established good clinical practice. Finally, in our study, SMR was higher in women in comparison to men, although statistically not significant. Clinical relevance of this finding is unclear at present. Prospective future studies with larger cohort and longer period of observation, incorporating data on right heart reverse remodelling and the potential effect of adjunct therapies to ASD closure such as ablation may shed additional light on the optimal management of this common congenital heart lesion.

    Conclusion

    Perioperative mortality and morbidity in a large contemporary adult cohort undergoing ASD closure, catheter or surgical, is extremely low. Mid to longer term survival is excellent irrespective of age at the time of ASD closure, gender and mode of closure, and similar to expected survival in matched general population.

    Key messages

    What is already known on this subject?

    • Atrial septal defect (ASD) is the most common congenital heart defect diagnosed in adulthood. Although it is considered a ‘simple’ defect, if untreated, ASD is associated with significant late morbidity and mortality. However, uncertainty exists regarding the survival benefits of ASD closure in adulthood, particularly in advanced age.

    What might this study add?

    • Contemporary closure of ASD, whether catheter or surgical, in a large, single tertiary centre is associated with low perioperative morbidity and no early mortality. Furthermore, our study shows excellent mid to longer term survival (over a median follow-up of 6.7 years) irrespective of age, gender and mode of closure, which is similar to expected survival of a matched general population.

    How might this impact on clinical practice?

    • Our data suggest that ASD closure should be considered irrespective of age, gender and required mode of closure. This study adds to previous evidence indicating safety of the ASD closure procedure, whether catheter or surgical, and of the potential survival benefits.

    Acknowledgments

    MB was a recipient of research grant from the EMAH Stiftung Karla Voellm, Krefeld, Germany. GPD, AK, MAG, AU, DS and the Adult Congenital Heart Centre and Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK, have received support from Actelion UK, Pfizer UK, GSK UK, the British Heart Foundation and the NIHR Cardiovascular and Respiratory Biomedical Research Units.

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    Footnotes

    • Contributors AU and GPD planned and conducted the study. MB, AK, MD, DS and MAG made substantial contributions to conception and design, analysis and interpretation of data. MB and MAG made substantial contribution to analysis, drafting the article and revising it critically for important intellectual content. All authors gave final approval of the version to be submitted and any revised version.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient consent Not required.

    • Ethics approval The study was approved by the Research and Governance Committee at our institution.

    • Provenance and peer review Not commissioned; externally peer reviewed.