Atrial septal defects

Authors, Journal, Affiliations, Type, DOI

• Tal Geva, Jose D Martins, Rachel M Wald
• The Lancet, 2014; 383:1921–1932
• Department of Cardiology, Boston Children's Hospital / Harvard Medical School, Boston MA USA; Hospital de Santa Marta, Centro Hospitalar Lisboa Central, Lisbon Portugal; Toronto Congenital Cardiac Centre for Adults, Peter Munk Cardiac Centre, University of Toronto, Canada
• Seminar (comprehensive review)
• https://doi.org/10.1016/S0140-6736(13)62145-5

Overview

This 2014 Lancet Seminar provides comprehensive foundational coverage of ASD pathophysiology, anatomy, natural history, and treatment across the lifespan, with particular depth on developmental embryology, pediatric natural history (spontaneous closure rates), and quantitative long-term surgical outcomes. ASD is identified as the third most common type of congenital heart disease (incidence 56/100,000 livebirths; recent echocardiographic estimates ~100/100,000). The review covers all ASD subtypes including the rare common atrium variant, provides granular spontaneous closure data by defect size, and reports 32-year surgical survival data stratified by age at repair. A key difference from later guidelines is the PVR threshold for closure: this review cites PVR <2/3 SVR (with PVR >8 WU generally precluding closure) based on ACC/AHA 2008 and ESC 2010 guidelines, compared to the more recent 5 WU threshold.

Keywords

Atrial septal defect, congenital heart disease, secundum, primum, sinus venosus, catheter closure, surgery, natural history, pulmonary hypertension, pregnancy

Key Takeaways

Incidence and Causes

• ASD: third most common type of CHD; estimated incidence 56/100,000 livebirths (traditional); ~100/100,000 with modern echocardiographic recognition of silent defects (sources/asd-lancet-2014 — high)
• Sex distribution by type: ~65–70% of secundum, ~50% of primum, ~40–50% of sinus venosus defects are female
• Most ASDs are sporadic; modes of inheritance in familial cases: primarily autosomal dominant
• Gene associations: NKX2-5, GATA4, TBX5, MYH6 (chromosome 14q12); NKX2-5 mutations specifically linked to secundum defects AND AV block
• Genetic syndromes: Holt-Oram (ASD in 66%), Down syndrome (secundum 42% + primum 39% of major CHD), Ellis van Creveld, Noonan, Budd-Chiari, Jarcho-Levine
• Maternal risk factors: fetal alcohol syndrome, first-trimester smoking, antidepressants (SSRIs, venlafaxine, paroxetine), diabetes, high dietary glycaemic index, advanced maternal age ≥35 years

Developmental Anatomy

• Atrial septation involves septum primum, septum secundum, and atrioventricular canal septum
• Fossa ovalis formed by: muscular boundaries from septum secundum + valve of fossa ovalis (septum primum)
• PFO = space between valve-competent septum primum and normally formed septum secundum; present in all newborns; complete anatomical closure in 70–75% of adults
• Sinus venosus septum: tissue separating right pulmonary veins from SVC and posterior/inferior right atrial free wall
• Coronary sinus septum: tissue separating coronary sinus from left atrium

Anatomy — ASD Subtypes

• Secundum ASD: defect within fossa ovalis (one or more defects in septum primum); septum secundum usually well-formed; size 2–3 cm range; not confluent with venae cavae, pulmonary veins, coronary sinus, or AV valves
• Primum ASD (partial AVSD): between anterior-inferior fossa ovalis margin and AV valves; common AV orifice with two distinct annuli; AV valves almost always abnormal (cleft anterior mitral leaflet); conduction axis displaced inferiorly (same as complete AVSD)
• Sinus venosus defect (~4–11% of ASDs): SVC type (87% of sinus venosus) between right upper pulmonary vein and SVC; less frequent involvement of posterior/inferior right atrium with right lower/middle pulmonary veins
• Coronary sinus defect: unroofing of coronary sinus–LA septum; associated persistent left SVC = Raghib syndrome
• Common atrium: absent septum primum + septum secundum + AV canal septum; often with heterotaxy syndrome; remnant septal tissue sometimes visible

Pathophysiology

• Left-to-right shunt direction and magnitude: defect size + relative ventricular compliance (both change with time)
• Haemodynamic pattern in secundum: shunt mostly during late ventricular systole and early diastole, increasing with atrial contraction and expiration
• Small defects (<10 mm): fairly small shunt, minimum/no right heart enlargement
• Large defects (Qp/Qs >1.5): volume overload → RV dilatation + diastolic septal shift towards LV → adverse interventricular interaction → decreased LV compliance + D-shaped short-axis geometry → decreased LV diastolic filling + increased Qp/Qs (self-reinforcing cycle)
• Late: LV systolic dysfunction can develop; impaired right atrial reservoir/pump function; RV myocardial cell hypertrophy, fibrosis, troponin-I elevation
• Pulmonary vascular bed: myointimal proliferation + increased medial smooth muscle + increased collagen → arteriolar narrowing and PH
• 6–19% of (mostly female) patients with large ASD develop pulmonary vascular disease over time

Natural History — Secundum Defect

• Spontaneous closure data (Hanslik 2006, n=200, median age 5 months, median follow-up 4.5 years):
  • 4–5 mm: 56% spontaneous closure
  • 6–7 mm: 30% spontaneous closure
  • 8–10 mm: 12% spontaneous closure

  • 10 mm: 0% spontaneous closure

  • Diagnosed <1 year: 39% closed vs 19% diagnosed later
• Change in defect size over time:
  • Initially ≤4 mm: 70% decrease, 12% unchanged, 18% increase
  • Initially >8–12 mm: 9% decrease, 15% unchanged, 76% increase
• Sinus venosus and primum defects: do not decrease in size; almost always require surgical closure
• Life expectancy (Campbell, untreated large secundum): annualised mortality 0.6–0.7%/yr in first two decades; rising to 4.5%/yr in 4th decade; 7.5%/yr in 6th decade
• ASD accounts for 25–30% of CHD diagnosed in adulthood

Clinical Presentation

• Most children asymptomatic through childhood; even large shunts may be asymptomatic until adulthood
• Incidental detection by murmur/ECG/CXR most common
• Second decade: subtle breathlessness on exertion or palpitations
• Adult patients with large defects: fatigue, exercise intolerance, palpitations, syncope, dyspnoea, oedema, thromboembolism, cyanosis
• Exercise capacity at 50–60% of predicted in adults with unrepaired secundum
• Arrhythmias: major arrhythmias uncommon in children; AF/flutter increase with age (atrial flutter 15% aged 40–60 yr; flutter 16% + AF 19% aged >60 yr); AV block associated with NKX2-5 mutations
• PH: uncommon in children with isolated ASD; mild–moderate PH common in adults with large defects; increases with age and altitude; Eisenmenger 5–10% of adults with untreated ASD; female:male ratio ~2; median age at severe PH diagnosis: 51 years (decades later than VSD)

Diagnosis

• Clinical: Wide fixed splitting of S2; soft systolic ejection murmur (pulmonary area); diastolic rumble (tricuspid flow); holosystolic murmur suggests primum or MVP
• ECG: tall P-wave, incomplete RBBB, right axis deviation; left axis deviation suggests primum
• CXR: right heart/PA enlargement; pulmonary plethora; central PA enlargement with peripheral paucity = pulmonary vascular obstructive disease
• TTE: primary diagnostic method; 2D + colour Doppler; 3DE for en-face defect views; limitations in restricted acoustic windows (obesity, large habitus, previous thoracic surgery) → TOE
• Contrast echo: agitated saline; coronary sinus defect with persistent left SVC → contrast appears in LA first when injected via left arm vein
• CMR: gold standard for ventricular volumes/function; phase velocity mapping for Qp/Qs; MR angiography for anomalous veins; seldom needed for isolated secundum/primum; important for sinus venosus defects (posterior location hampers TTE in adults)
• CT: high-resolution anatomy; cancer risk of ionising radiation limits use to carefully selected patients
• Catheterisation: rarely for diagnosis alone; usually combined with device closure intention; diagnostic in selected adults (CAD risk, PH); angiography for associated anomalies

Treatment — Indications for Closure

• Class I indication: haemodynamically significant shunt causing right heart enlargement, irrespective of symptoms (Class I/B)
• Class IIa: suspicion of paradoxical embolism without other cause
• Class IIa: orthodeoxia-platypnoea (dyspnoea/hypoxaemia on sitting/standing from recumbent position) irrespective of shunt size
• Small defect without RV volume overload: follow expectantly; shunt may increase with age
• PAH — closure thresholds (per ACC/AHA 2008 and ESC 2010):
  • Closure permitted if PVR <2/3 SVR (at baseline or after pulmonary vasodilator acute challenge or pretreated course) + Qp/Qs >1.5 (Class IIb/C)
  • PVR >8 WU generally precludes closure
  • Resting right-to-left shunt (Eisenmenger syndrome): closure contraindicated
  • Pop-off valve situations (severe obstructive/restrictive RV/LV lesions): closure may be contraindicated
  • PH patients: careful evaluation in experienced centre including balloon occlusion test
• Timing: electively once diagnosed; many clinicians refer asymptomatic children at age 3–5 years; closure is safe and improves symptoms even in elderly patients
• Defect type and closure route: sinus venosus, primum, coronary sinus → surgical; secundum → surgery or transcatheter

Transcatheter Device Closure — Outcomes and Complications

• King et al. 1976: first transcatheter device closure reported
• Current contraindications: >36–40 mm maximum diameter, inadequate margins, interference with AV valves or venous drainage; small infants
• Guidance: fluoroscopy + echocardiography (TOE 2D/3D, ICE, or TTE); femoral vein approach
• Amplatzer septal occluder results (multicenter, n=478, median age 6 yr): technical success 96%; occlusion at 24h 99.6%
• Adult cohort (n=650, mean age 45 yr): similarly good early results
• HELEX device (multicenter prospective): procedural success 93%; closure rate 98.1%
• Complications inversely related to institutional procedural volume
• Meta-analysis (28,142 patients, 203 studies): Major periprocedural complications 1.6% (95% CI 1.4–1.8); device embolisation requiring surgery 0.7%; pericardial tamponade 0.1%
• Minor complications: atrial arrhythmias, vascular complications, transient heart block
• Late complications: atrial arrhythmias 1.5%, stroke 0.4%, device thrombosis 0.2%, cardiac erosion through atrial wall or aortic root 0.1%, device embolisation 0.1%, death 0.1%
• Cardiac erosion by device: subject of multiple reports and FDA review
• Nickel allergy: new-onset/worsening migraine in some patients; clopidogrel may help
• Antiplatelet drugs routinely prescribed post-device implantation but supporting data lacking
• No prospective RCT comparing transcatheter vs surgical closure for secundum ASD

Surgical Closure — Outcomes

• Near-zero mortality for isolated defect closure in modern era
• Surgical approach options: median sternotomy, submammary incision, lateral thoracotomy, transxiphoid, video-assisted thoracoscopic
• Murphy et al. long-term follow-up (27–32 years) — survival vs general population:
  • Operated <12 yr: 98% vs 99% (excellent; near-normal)
  • Operated 12–24 yr: 93% vs 97% (slightly reduced)
  • Operated 25–41 yr: 84% vs 91% (meaningfully reduced)
  • Operated >41 yr: 40% vs 59% (substantially reduced)
• Morbidities (arrhythmias, bleeding, pneumothorax, pericardial/pleural effusions) usually transient
• Arrhythmia and prolonged ICU stay (>3 days) more common in adults/elderly

Clinical and Haemodynamic Results of Closure

• Subjective symptom improvement common post-closure
• Somatic growth rate can increase in young children
• Exercise capacity: improved in adults (especially those >40 yr with initial reduction); minimum change in asymptomatic children
• RV remodelling: most of the decrease occurs immediately, with further remodelling 1–2 years later
• Younger age at closure + lesser pre-repair chamber enlargement → higher likelihood of RV size normalisation
• Persistent RV enlargement: up to 1/3 of patients (mostly adults with severely dilated chambers)
• LV filling improves in children and young adults; risk of worsening LA/PV hypertension in adults with decreased LV compliance post-closure
• PA pressure: decreases to normal except in some patients with moderate–severe PH
• Arrhythmia meta-analysis (26 studies, 1841 surgical + 945 transcatheter closures): OR 0.66 (0.57–0.77) in short term; beneficial effect LOST when only studies with ≥5 years follow-up considered
• Persistent rhythm/conduction abnormalities with delayed closure: Maze procedure considered in selected adults (AHA/ESC)

Adults with Repaired Defects

• Closure after age 40 confers morbidity/mortality benefits vs medical therapy alone
• Benefits less pronounced after age 60; QoL improvement and 6MWD increase with low procedural risk justify closure in elderly
• Risk of atrial tachyarrhythmias remains HIGH after adult closure; risk factors: pre-closure AF/flutter; age at closure >40 years

Pregnancy

• Maternal complications uncommon in ASD without PH: arrhythmias 4%; TIA 1%; no stroke/HF/endocarditis in 98 women with 188 pregnancies (Yap/ZAHARA)
• Pre-pregnancy arrhythmia history and age >30 years: risk factors for maternal cardiac complications
• Unrepaired ASD: increased risk of pre-eclampsia, fetal loss, and low birthweight vs general population
• Repaired ASD: offspring outcomes similar to general population
• ASD + PH: pregnancy associated with 28% maternal mortality despite pulmonary vasodilator therapy in >50%; deaths peripartum from HF, thromboembolism, pulmonary hypertensive crisis, SCD

Limitations of the Document

• Literature search covers only Jan 2003 – April 2013; does not include evidence from 2014 onwards
• PVR thresholds cited (>8 WU precluding closure) reflect ACC/AHA 2008 and ESC 2010 guidelines — these differ from more recent ESC 2020 guideline thresholds (≥5 WU contraindication)
• No randomised trials comparing transcatheter vs surgical closure for secundum ASD existed at time of writing
• Natural history data (Campbell; Murphy) pre-date modern GDMT, contemporary device closure, and contemporary surgical techniques
• Spontaneous closure data (Hanslik) from a single centre cohort in predominantly young children; may not generalise to all populations

Key Concepts Mentioned

• concepts/Atrial-Septal-Defect — primary subject; spontaneous closure rates, PVR thresholds, surgical survival, device complication data added
• concepts/ACHD-AP-Classification — ASD classification context
• concepts/Pulmonary-Hypertension — PVR threshold for closure (different from Brida 2022)

Key Entities Mentioned

• entities/Atrial-Fibrillation — arrhythmia outcome data post-closure

Wiki Pages Updated

• wiki/sources/asd-lancet-2014.md — created (this file)
• wiki/concepts/Atrial-Septal-Defect.md — updated with spontaneous closure data, surgical survival, device complication rates, PVR contradiction
• wiki/wikiindex.md — source entry updated
• wiki/sourceindex.md — new source entry added