Atrial septal defect in adulthood: a new paradigm for congenital heart disease

Authors, Journal, Affiliations, Type, DOI

• Margarita Brida, Massimo Chessa, David Celermajer, Wei Li, Tal Geva, Paul Khairy, Massimo Griselli, Helmut Baumgartner, Michael A. Gatzoulis
• European Heart Journal, 2022; 43:2660–2671
• Royal Brompton & Harefield Hospitals / Imperial College London; Zagreb University Hospital; University of Sydney; Boston Children's Hospital / Harvard Medical School; Montreal Heart Institute; University of Minnesota; University Hospital Muenster
• State of the Art Review
• https://doi.org/10.1093/eurheartj/ehab646

Overview

Atrial septal defect (ASD) is the most common congenital heart defect diagnosed in adulthood, accounting for 25–30% of new CHD diagnoses, due to its slow clinical progression and frequent asymptomatic presentation in younger years. The review presents a new paradigm: proactive closure at the time of diagnosis — before overt symptoms — has normalized prognosis for young adults and improved quality of life across all age groups, irrespective of age. Key challenges remain in patients with pulmonary arterial hypertension (PVR thresholds), pre-existing atrial fibrillation (optimal sequencing of ablation and closure), and those with sinus venosus defects requiring surgical or emerging catheter techniques. Lifelong follow-up is warranted in most adult patients for late complications including arrhythmias, heart failure, and incomplete right ventricular remodelling.

Keywords

Atrial septal defect, congenital heart disease, pulmonary arterial hypertension, catheter closure, surgical closure, arrhythmia, cardiac remodelling

Key Takeaways

Cause and Anatomy

• Most ASDs are sporadic; genetic associations include Down syndrome (~80%), Holt-Oram (~65%), Ellis van Creveld (~60%), Noonan (~20%) syndromes; implicated genes include NKX2-5, GATA4, TBX5
• Maternal exposures associated with ASD: alcohol, smoking, antidepressants (SSRIs), diabetes
• Four ASD subtypes:
  • Secundum ASD (80%): fossa ovalis; most amenable to device closure
  • Primum ASD / partial AVSD (15%): adjacent to AV valves; always abnormal AV valve morphology; surgical repair required
  • Sinus venosus ASD (superior ~5%; inferior <1%): near SVC/IVC; often with anomalous pulmonary venous drainage; predominantly surgical; emerging catheter stent techniques
  • Coronary sinus defect (rarest): associated with persistent left SVC (Raghib syndrome)
• Small secundum ASD must be distinguished from patent foramen ovale (PFO), which is not a true atrial septal tissue deficiency

Pathophysiology

• Left-to-right shunt magnitude determined by defect size and relative ventricular compliance
• Small defects (<10 mm): minimal or no RV enlargement
• Large, long-standing shunts → right atrial and RV dilatation, myocardial stretch/injury, and increased pulmonary blood flow → shear stress → PAH (pulmonary vascular disease relatively rare)
• Rise in PAP with age is common; overt PAH is less common but more prevalent in sinus venosus defects and with advanced age

Natural History

• Untreated: three-quarters of patients died by age 50 (pre-surgical era data)
• Worst prognosis with primum ASDs (high death rates >30 yr)
• Contemporary series: closure in adulthood associated with normal mid-to-longer term survival irrespective of age (Brida 2019 Heart; Abrahamyan 2021 JACC CI)
• Closure before age 25 yr: excellent long-term prospects and normal survival
• Morbidity increases with advancing age at closure, but symptomatic benefits observed at all ages

Diagnostic Workup

• Typical presentation: heart murmur or abnormal ECG/CXR in young adults; later: breathlessness/palpitations
• ECG: incomplete RBBB, tall P-wave (right atrial enlargement), superior axis in primum ASD
• CXR: right heart enlargement, pulmonary plethora
• Echocardiography (first-line):
  • TTE: 2D + colour Doppler; RV enlargement with normal/hyperdynamic function = sign of significant ASD
  • TOE: essential for suboptimal TTE window, sinus venosus defect, intraprocedural guidance
  • 3DE: defect characterisation, rim assessment, device sizing
  • Fusion TOE + fluoroscopy: emerging intraprocedural tool
  • ICE: increasingly replaces TOE at some centres; no general anaesthesia required
• CMR: gold standard for ventricular volumes; phase contrast for Qp/Qs; essential for sinus venosus defects (especially inferior)
• CT: high-resolution anatomy with radiation <1 mSv; indicated when echocardiography insufficient
• Advanced imaging: 3D printing, computational modelling, holographic AR (HoloLens) for sinus venosus planning
• Cardiac catheterisation: NOT routinely required; mandatory when PH suspected (estimated sPAP >40 mmHg), LV dysfunction, or CAD evaluation in older patients

Catheterisation Thresholds for ASD Closure in PAH

• PVR <5 WU: closure safe; associated with reduced PAP and symptom improvement (extent inversely related to PVR)
• PVR ≥5 WU: unlikely to improve and may worsen after closure → avoid complete closure; consider PAH pharmacotherapy and re-evaluate
• PVR ≥5 WU after PAH therapy + significant L→R shunt (Qp/Qs >1.5): fenestrated closure may have merits (long-term impact unknown)
• PVR ≥5 WU despite PAH treatment: ASD closure contraindicated
• Vasoreactivity testing with inhaled NO is NOT recommended when deciding whether to close ASD in PAH
• Left ventricular impairment (systolic/diastolic): invasive haemodynamic assessment mandatory; balloon test occlusion before device deployment to assess PCWP increase; complete, fenestrated, or no closure based on haemodynamics

Treatment

Catheter Closure

• Treatment of choice for most secundum ASDs — excellent outcomes (low complications, shorter stay vs surgery)
• Guidance: fluoroscopy + TOE (or ICE); balloon sizing debated
• Anatomic contraindications to device closure: insufficient rims, very large defect, excessively bulging aneurysm; isolated absent aortic rim can often be overcome
• Devices: non-degradable shape memory alloy occluders (Amplatzer-type); biodegradable devices in development
• Sinus venosus ASD catheter closure (emerging): covered stent deployment (Cheatham-platinum); requires balloon test inflation to confirm unobstructed pulmonary venous drainage; no mortality but early stent embolisation/haemopericardium/PV occlusion described; surgical closure remains standard of care

Surgical Closure

• Indicated for sinus venosus, primum, coronary sinus defects, and secundum not amenable to device closure
• Traditional median sternotomy vs minimally invasive approaches (mini-sternotomy, thoracotomy, robotic-assisted endoscopic)
• Outcomes: mortality <1%; major complications <7%; most common complication is postoperative arrhythmia
• Hospital stay rarely >4–5 days

Medical Therapy

• PAH therapy: oral endothelin-receptor antagonist and/or PDE5 inhibitor when PVR ≥5 WU
• "Treat-and-repair" approach: limited evidence for long-term benefit
• For Eisenmenger syndrome: proactive advanced PAH therapy including prostacyclins; subcutaneous/inhaled preferred over parenteral (avoid paradoxical embolism risk)
• Antiarrhythmic drugs, anticoagulation, diuretics: standard measures per underlying complication
• AF thromboprophylaxis: CHA₂DS₂-VASc/HAS-BLED guided; DOACs may be considered (limited CHD-specific data)

Arrhythmias

• Atrial flutter and AF prevalence increases steeply with age: ~20% atrial flutter, >50% AF by age 60
• Right atrial electrophysiological alterations (reduced voltage, prolonged refractory periods, spatial conduction heterogeneity); Bachmann's bundle conduction disturbances implicated in AF substrate
• Impact of ASD closure on AF is controversial:
  • Meta-analysis (25 studies): percutaneous closure NOT associated with reduction in atrial arrhythmias
  • Some data suggest closure <40 yr protective; others report neutral or proarrhythmic effects
  • Persistent AF unlikely to be affected; paroxysmal AF may improve with a likelihood decreasing with age
  • No compelling rationale for AF to be an indication for closure, or to select one closure approach over another
• Key recommendation: for adults with AF + newly diagnosed ASD meeting closure criteria, catheter ablation BEFORE percutaneous closure whenever possible
  • Freedom from post-closure AF: 79% with pre-closure ablation vs 37% without
  • Closing ASD first increases complexity of trans-septal access (though still feasible in most cases; 90–98% success)
• Sinus node dysfunction more prevalent with superior sinus venosus defects
• AV block more frequent in primum defects (inferiorly displaced AV conduction system)

Cardiac Remodelling After Closure

• Haemodynamic and cardiac remodelling begins almost immediately but continues ≥1 year
• Extent of RV reverse remodelling inversely related to age at closure
• RVESVI >75 mL/m² at closure → persistent right heart dilatation, residual tricuspid regurgitation, elevated BNP, RV dysfunction
• Older patients with late closure: higher prevalence of persistent RV dilatation and functional TR

Heart Failure

• Right heart volume overload depends on defect size and relative LV:RV compliance (increases as LV stiffens with age, hypertension, CAD)
• Atrial tachyarrhythmias may accelerate chronic HF and precipitate decompensation
• PAH + volume-loaded RV → exaggerated RV dysfunction
• Primum ASD: left AV valve regurgitation can be a significant contributor requiring re-operation

Pulmonary Hypertension and Eisenmenger Syndrome

• PH complicating ASD: increases with advanced age; more common in sinus venosus defects; loosely correlates with larger defect size
• Contemporary series: PH in <3% of closed defects (reflects earlier diagnosis and proactive closure approach)
• Eisenmenger syndrome (severe pulmonary vascular disease): historically 5–10% of adults with untreated defects; more common in women; rare nowadays
• ASD closure in Eisenmenger syndrome: contraindicated

Stroke

• ASD patients: increased stroke risk (~4% with open defects; 1.4% with closed defects)
• Open ASD: paradoxical embolism primary mechanism
• Closed ASD: residual risk from AF and/or pulmonary venous remodelling
• Older patients: anticoagulation for 6–12 months post-closure considered irrespective of pre-procedural AF

Pregnancy

• Well tolerated in uncomplicated ASD; small risk of paradoxical embolus/stroke → advise closure before conception
• Uncomplicated ASD diagnosed during pregnancy: continue pregnancy, close electively post-partum
• Repaired ASD: pregnancy outcomes similar to general population
• ASD + PAH: pregnancy risks prohibitive; effective contraception and discussion of alternatives (surrogacy/adoption) required

Follow-Up Care

• Lifelong ACHD specialist follow-up needed, particularly for late closure patients (incomplete RV remodelling), primum ASD (AV valve problems), and small defects with surveillance for progression
• Transition from paediatric to adult CHD services essential; lapse of care → increased morbidity/mortality

Limitations of the Document

• State-of-the-art review (not systematic review/meta-analysis); no formal GRADE methodology
• Natural history data largely from pre-echocardiography era studies — some uncertainty about full spectrum of outcomes
• No randomised trial data on vasoreactivity testing in ASD-PAH decision-making
• Arrhythmia impact of closure data based on non-randomised, observational/meta-analytic evidence
• Sinus venosus catheter closure data very limited (small series, mostly case reports); surgical closure remains gold standard
• Treat-and-repair evidence for ASD-PAH is limited and long-term outcomes unknown

Key Concepts Mentioned

• concepts/Atrial-Septal-Defect — primary subject of review
• concepts/ACHD-AP-Classification — ASD classification (Class I Simple anatomically)
• concepts/Pulmonary-Hypertension — PVR thresholds for ASD closure
• concepts/Arrhythmogenic-Cardiomyopathy — contrast with ASD-related remodelling
• concepts/PAH-Risk-Stratification — PAH assessment in ASD
• concepts/SVT-Management — AF management in ASD context

Key Entities Mentioned

• entities/Atrial-Fibrillation — most common arrhythmia in ASD adults
• entities/CTEPH — differential for PH in ASD patients

Wiki Pages Updated

• wiki/sources/asd-ehj-2022.md — created (this file)
• wiki/concepts/Atrial-Septal-Defect.md — created new concept page
• wiki/concepts/ACHD-AP-Classification.md — added ASD source reference and closure thresholds
• wiki/concepts/Pulmonary-Hypertension.md — added ASD-PAH section
• wiki/wikiindex.md — new ASD entry added
• wiki/sourceindex.md — new source entry added