Home Cardiology Congenital Heart Disease: PFO, ASD & VSD

Congenital Heart Disease: PFO, ASD & VSD

📋 Key Information Summary

📋
  • Patent foramen ovale (PFO) is present in ~25% of the general population and is the most common right-to-left shunt; it is strongly implicated in cryptogenic stroke in patients <60 years.
  • PFO closure is indicated for cryptogenic stroke aged 18–60 years after multidisciplinary discussion; meta-analyses (RESPECT, REDUCE, CLOSE, DEFENSE-PFO) demonstrate absolute risk reduction of ~3–5% over medical therapy alone.
  • Atrial septal defects (ASDs) account for 10–15% of congenital heart defects; secundum ASD is most common (~75%) and often amenable to device closure.
  • Small ASDs with no right-heart volume overload may be observed; closure is indicated when right ventricular dilatation (Qp:Qs ≥ 1.5:1) or paradoxical embolism occurs.
  • Ventricular septal defects (VSDs) are the most common congenital heart defect at birth (~30%); 30–50% of small muscular VSDs close spontaneously by age 5.
  • Large VSDs cause pulmonary overcirculation and heart failure in infancy; surgical closure is recommended if symptoms persist despite optimal medical therapy or Qp:Qs ≥ 2:1.
  • Eisenmenger syndrome (irreversible pulmonary arterial hypertension with shunt reversal) is the most feared complication of unrepaired large shunts — once established, closure is contraindicated.
  • All patients require endocarditis prophylaxis education; lifelong endocarditis prophylaxis is indicated only for those with prior endocarditis, prosthetic material, or cyanotic CHD.
  • Echocardiography (TTE ± TOE with bubble study) is the primary diagnostic tool; cardiac MRI/catheterisation used for quantification and pre-intervention planning.
  • Aboriginal and Torres Strait Islander peoples have higher prevalence of rheumatic heart disease-related valve lesions and may present later with shunt-related complications — early echocardiographic screening is essential.

Introduction & Australian Epidemiology

Atrial and ventricular septal defects are the most common congenital heart defects encountered in both paediatric and adult cardiology practice. The patent foramen ovale (PFO), atrial septal defect (ASD), and ventricular septal defect (VSD) represent a spectrum of intracardiac shunts ranging from clinically insignificant communications to haemodynamically significant lesions requiring intervention.

In Australia, congenital heart disease affects approximately 8–10 per 1 000 live births, with isolated septal defects comprising a substantial proportion. Most small ASDs and many muscular VSDs close spontaneously during early childhood; however, larger defects with significant left-to-right shunting (Qp:Qs ≥ 1.5–2.0) lead to volume overload, ventricular remodelling, pulmonary arterial hypertension, and — if unrepaired — Eisenmenger syndrome.

The recognition of PFO as a causal mechanism in cryptogenic stroke has driven a paradigm shift in secondary stroke prevention, supported by landmark randomised trials. Simultaneously, advances in transcatheter device closure have expanded treatment options for secundum ASD and selected VSDs, reducing the need for open-heart surgery in many patients.

This guideline addresses the pathophysiology, diagnosis, risk stratification, and evidence-based management of PFO, ASD, and VSD in the Australian context, including special considerations for Aboriginal and Torres Strait Islander populations, pregnancy, and the transition from paediatric to adult congenital heart services.

Defect Prevalence Spontaneous Closure Key Risk
PFO ~25% of adults N/A (functional valve) Paradoxical embolism → cryptogenic stroke
Secundum ASD 1–2 per 1 000 live births Small defects may close <2 yrs RV volume overload, AF, paradoxical embolism
VSD ~3 per 1 000 live births 30–50% of muscular VSDs by age 5 LV failure, pulmonary hypertension, Eisenmenger
Congenital Heart Disease: PFO, ASD & VSD clinical infographic — pathophysiology, clinical clues, diagnosis, imaging, and management
Tap or click image to enlarge — Congenital Heart Disease: PFO, ASD & VSD: pathophysiology, clinical clues, diagnosis, imaging, and management.
Congenital Heart Disease: PFO, ASD & VSD infographic, full size

Patent Foramen Ovale (PFO) & Cryptogenic Stroke

Pathophysiology

The foramen ovale is a normal fetal structure that facilitates right-to-left shunting of blood. In approximately 25% of adults, the septum primum and secundum fail to fuse completely, leaving a flap-valve communication that opens transiently during increases in right atrial pressure (Valsalva manoeuvre, coughing, prolonged standing). This allows paradoxical embolisation of venous thrombi, fat, or air into the systemic arterial circulation.

Clinical Presentation & Diagnostic Criteria

PFO is usually asymptomatic and discovered incidentally. The clinical scenario requiring investigation is cryptogenic stroke — defined as ischaemic stroke where standard workup (including 24-hour Holter, carotid imaging, basic coagulation screen) does not reveal an aetiology. Cryptogenic stroke accounts for 25–40% of all ischaemic strokes.

⚠️
RoPE Score (Risk of Paradoxical Embolism): A validated tool to estimate the probability that a PFO is stroke-causal rather than incidental. High RoPE score (≥7) in a patient aged <60 with cryptogenic stroke strongly favours PFO as the mechanism. Absence of vascular risk factors (hypertension, diabetes, smoking) further increases PFO-attributable fraction.

Investigations

Essential
Transthoracic echocardiography (TTE) with agitated saline (bubble study)
Sensitivity ~60% for PFO detection; positive if ≥3 microbubbles cross to left atrium within 3 cardiac cycles. MBS item 55118.
Available
Transoesophageal echocardiography (TOE) with bubble study ± Valsalva
Gold standard; sensitivity >90%. Defines PFO size, tunnel length, and presence of atrial septal aneurysm (ASA). MBS item 55121.
Available
Transcranial Doppler (TCD) with bubble study
High sensitivity (>95%) but cannot differentiate PFO from intrapulmonary shunt. Useful screening when TOE not immediately available.
Available
Brain MRI with DWI
Confirms ischaemic stroke territory; small cortical or multi-territory infarcts favour embolic mechanism.
Referral
Prolonged cardiac monitoring (14–30 day patch or implantable loop recorder)
Essential to exclude occult atrial fibrillation before attributing stroke to PFO.

Risk Stratification — PFO-Associated Stroke

Low-risk features
Medical therapy likely sufficient
Age >60, RoPE <6, small PFO (<2 mm), no ASA, conventional vascular risk factors present, single small cortical infarct.
Setting: Outpatient neurology + cardiology
Intermediate features
MDC discussion recommended
Age 40–60, RoPE 6–7, moderate PFO, coexisting ASA, single episode, some vascular risk factors.
Setting: MDC — Adult Congenital Heart / Stroke service
High-risk features — favour closure
PFO closure strongly recommended
Age <60, RoPE ≥7, large PFO (≥2 mm), ASA, hypermobile septum, tunnel >10 mm, recurrent stroke on antiplatelet, cortical infarct in multiple territories, no conventional risk factors.
Setting: Tertiary cardiac centre — catheter lab

Management

Medical Therapy

💊
Aspirin
Aspro Clear® · Cardiprin® · Antiplatelet
Adult dose 100 mg PO daily
Paediatric dose 1–5 mg/kg/day PO (max 100 mg)
PBS status ✔ PBS General Benefit
💊
Clopidogrel
Plavix® · Iscover® · Antiplatelet
Adult dose 75 mg PO daily
PBS status ✔ PBS General Benefit

Percutaneous PFO Closure

Percutaneous PFO closure is performed via right femoral vein access using a nitinol double-disc device (e.g., Amplatzer™ PFO Occluder, Gore Cardioform™). The procedure is performed under TOE or intracardiac echocardiography (ICE) guidance, typically under general anaesthesia.

Indication for PFO closure (Australian context): Cryptogenic ischaemic stroke or systemic embolism in patients aged 18–60 years, with PFO confirmed on TOE, after exclusion of other causes (including AF on prolonged monitoring), and after multidisciplinary team discussion including neurologist, cardiologist, and adult congenital heart specialist.

Post-closure, dual antiplatelet therapy (aspirin 100 mg + clopidogrel 75 mg daily) is prescribed for 1–6 months, followed by aspirin monotherapy for at least 5 years. Device thrombosis risk is <1%. Endocarditis prophylaxis is not routinely required after isolated PFO closure.

Atrial Septal Defect (ASD): Types & Management

Types & Anatomy

Type % of ASDs Location Associated Features
Secundum ~75% Fossa ovalis region Most common; amenable to device closure
Primum ~15–20% Lower atrial septum, adjacent to AV valves Cleft mitral valve → MR; part of AVSD spectrum
Sinus venosus ~5–10% Superior (SVC junction) or inferior (IVC junction) Partial anomalous pulmonary venous drainage (PAPVD)
Coronary sinus <1% Roof of coronary sinus Often associated with persistent left SVC

Pathophysiology

ASDs create a left-to-right shunt at the atrial level. The magnitude depends on defect size, ventricular compliance differences, and pulmonary vascular resistance. Chronic right ventricular volume overload leads to RV dilatation, tricuspid regurgitation, atrial arrhythmias (particularly atrial flutter and fibrillation — prevalence rises sharply after age 40), and ultimately pulmonary arterial hypertension if the shunt is large and unrepaired.

Clinical Presentation

  • Children: Often asymptomatic; may present with murmur (systolic ejection murmur at left upper sternal border with wide, fixed splitting of S2), poor weight gain, or recurrent respiratory infections.
  • Adults: Exertional dyspnoea, fatigue, palpitations (atrial arrhythmias), paradoxical embolism/stroke, or right heart failure symptoms.
  • Elderly: Presentation with AF, heart failure, or pulmonary hypertension is common due to delayed diagnosis.

Investigations

Essential
Transthoracic echocardiography (TTE)
Defines ASD type, size, shunt direction; assesses RV size and function (TAPSE, fractional area change). MBS item 55118.
Available
Transoesophageal echocardiography (TOE)
Superior for sinus venosus and primum ASDs; mandatory pre-device closure to assess rims. MBS item 55121.
Available
Cardiac MRI
Accurate Qp:Qs quantification; identifies PAPVD in sinus venosus defects; useful when echo windows poor. MBS item 63001 series.
Available
Right heart catheterisation
Direct measurement of Qp:Qs and pulmonary artery pressures; required pre-intervention if PAH suspected or Qp:Qs borderline.
Available
12-lead ECG
Incomplete RBBB common; primum ASD shows left axis deviation; sinus venosus may show ectopic atrial rhythm.

Indications for Closure

⚠️
Closure is indicated when:
  • Right ventricular volume overload on echocardiography (RV dilatation), regardless of symptoms
  • Qp:Qs ≥ 1.5:1 with evidence of RV enlargement
  • Paradoxical embolism with haemodynamically significant ASD
  • Symptomatic patients (exertional dyspnoea, arrhythmias) attributable to the shunt
Closure is NOT indicated if: Eisenmenger physiology (irreversible pulmonary hypertension with pulmonary vascular resistance >2/3 systemic, or right-to-left shunt at rest).

Management

Transcatheter Device Closure (Secundum ASD)

Secundum ASDs with adequate rims (≥5 mm from mitral valve, aortic root, SVC, IVC, and right upper pulmonary vein) are suitable for percutaneous device closure using the Amplatzer™ Septal Occluder or similar nitinol double-disc device. Procedure success rate exceeds 95%. Day-case or overnight stay.

Post-closure: Aspirin 100 mg daily for 6 months. Echocardiography at 24 hours, 1 month, 6 months, and 12 months to assess device position and residual shunt. Endocarditis prophylaxis for 6 months post-device implantation only.

Surgical Closure

Indicated for primum ASD (with cleft mitral valve repair), sinus venosus ASD (with PAPVD rerouting), coronary sinus ASD, and secundum ASDs unsuitable for device closure (inadequate rims, very large defects >38 mm, or multiple defects). Performed via median sternotomy or right anterolateral minithoracotomy on cardiopulmonary bypass. Operative mortality <1% in experienced centres.

Medical Therapy (Non-closure Candidates)

💊
Diuretic therapy for RV failure
Frusamide® · Diurin® · Loop diuretic
Adult dose 20–80 mg PO/IV daily, titrate to symptoms
Renal adjustment No fixed dose reduction; monitor eGFR and electrolytes closely
PBS status ✔ PBS General Benefit
💊
Rate control for AF
Bisoprolol · Beta-blocker
Adult dose 2.5–10 mg PO daily
PBS status ✔ PBS General Benefit

Ventricular Septal Defect (VSD): Types & Management

Types & Anatomy

Type % of VSDs Location Closure Potential
Perimembranous (outlet) ~70–80% Membranous septum, adjacent to aortic valve Small defects may close via tricuspid tissue apposition; device closure possible but higher risk of conduction injury
Muscular ~5–20% Muscular septum (inlet, trabecular, or outlet) Highest spontaneous closure rate (30–50% by age 5)
Inlet ~5–8% Posterior septum near AV valves Associated with AVSD; requires surgical repair
Doubly-committed subarterial ~5–7% (higher in Asian populations) Outlet septum beneath both semilunar valves Spontaneous closure rare; risk of aortic valve prolapse and regurgitation

Pathophysiology

VSDs create a left-to-right shunt at the ventricular level. Shunt volume depends on defect size relative to the aortic root and systemic vascular resistance. Small restrictive VSDs (diameter < one-third of the aortic root) generate high-velocity jets and are usually well tolerated. Large non-restrictive VSDs equalise ventricular pressures, causing pulmonary overcirculation, biventricular volume overload, and — if unrepaired — progressive pulmonary vascular obstructive disease (Eisenmenger syndrome).

Clinical Presentation

  • Small VSD: Usually asymptomatic; loud pansystolic murmur at left lower sternal border (grade 3–4/6 with thrill). Often detected on neonatal or infant examination.
  • Moderate VSD: Failure to thrive, tachypnoea, diaphoresis with feeds in infancy; murmur with possible S3 gallop (volume-loaded LV).
  • Large VSD: Congestive heart failure from 4–6 weeks of age; tachycardia, tachypnoea, hepatomegaly, poor feeding. May progress to Eisenmenger if unrepaired — progressive cyanosis, clubbing, exercise limitation.

Investigations

Essential
Transthoracic echocardiography (TTE)
Defines VSD type, size, shunt velocity (CW Doppler), LV/RV pressures, and ventricular dimensions. MBS item 55118.
Available
Cardiac MRI
Accurate Qp:Qs and ventricular volumes; helpful for multiple or complex VSDs. MBS item 63001 series.
Referral
Cardiac catheterisation with oximetry run
Qp:Qs calculation and pulmonary vascular resistance assessment; mandatory before repair if PAH suspected or Qp:Qs borderline.
Available
Chest X-ray
Cardiomegaly, pulmonary plethora in large VSDs; may show pulmonary artery dilatation.

Indications for Closure

⚠️
Surgical VSD closure is indicated when:
  • Symptomatic heart failure refractory to medical therapy in infancy (most large VSDs repaired by 3–6 months)
  • Qp:Qs ≥ 2:1 regardless of symptoms
  • Evidence of progressive LV volume overload or pulmonary hypertension
  • Aortic valve prolapse or regurgitation associated with doubly-committed or perimembranous VSD
Percutaneous device closure is an option for selected muscular VSDs (post-MI VSD, congenital muscular VSD) and in some perimembranous VSDs — however, higher rates of complete heart block necessitate careful patient selection and procedural expertise.

Management

Medical Therapy (Bridge to Surgery or Palliative)

💊
Furosemide
Lasix® · Frusamide® · Loop diuretic
Paediatric dose 0.5–2 mg/kg/dose PO/IV BD–TDS
PBS status ✔ PBS General Benefit
💊
Captopril
Capoten® · ACE inhibitor
Paediatric dose 0.1–0.5 mg/kg/dose PO TDS (max 2 mg/kg/day)
Adult dose 12.5–50 mg PO TDS
PBS status ✔ PBS General Benefit
💊
Spironolactone
Aldactone® · Kaldium® · Aldosterone antagonist
Paediatric dose 1–3 mg/kg/day PO in divided doses
PBS status ✔ PBS General Benefit

Surgical VSD Closure

Open-heart surgical patch closure (using Dacron or pericardium) is the standard approach for most significant VSDs. Performed via median sternotomy on cardiopulmonary bypass. Operative mortality <1% in experienced paediatric cardiac centres. Risk of complete heart block is ~1% (highest with perimembranous VSDs). Post-operative endocarditis prophylaxis for 6 months only.

Transcatheter Device Closure

Percutaneous closure using the Amplatzer™ Muscular VSD Occluder is available for muscular VSDs and selected post-infarct VSDs. Perimembranous VSD device closure carries a ~3–5% risk of complete heart block and is only performed at select tertiary centres in Australia. Conduction complications may present months after the procedure — long-term follow-up is essential.

Haemodynamic Consequences (Qp:Qs)

Understanding the Pulmonary-to-Systemic Flow Ratio

The Qp:Qs ratio quantifies the magnitude of intracardiac shunting. It is calculated as the ratio of pulmonary blood flow (Qp) to systemic blood flow (Qs). A ratio of 1.0 indicates no shunt. A ratio >1.0 indicates left-to-right shunting; <1.0 indicates right-to-left shunting.

Qp:Qs = 1.0
No significant shunt
Haemodynamically insignificant. Small restrictive defects. Observation and follow-up appropriate.
Qp:Qs 1.0–1.5
Small shunt
Mild volume overload. Serial echocardiographic monitoring. Closure generally not indicated unless other risk factors (paradoxical embolism, arrhythmias).
Qp:Qs 1.5–2.0
Moderate shunt — closure threshold
Significant right or left ventricular volume overload. Closure indicated when RV or LV dilatation confirmed on echo or MRI.
Qp:Qs ≥ 2.0
Large shunt — strong indication for closure
Marked ventricular volume overload, risk of pulmonary hypertension progression. Surgical or device closure recommended. Eisenmenger risk if chronically unrepaired.
Qp:Qs < 1.0
Right-to-left shunt — Eisenmenger physiology
Pulmonary vascular resistance exceeds systemic. Cyanosis, right heart failure. Closure contraindicated. Pulmonary vasodilator therapy and transplant assessment indicated.

Eisenmenger Syndrome

🚨
Eisenmenger syndrome = closure contraindicated. If irreversible pulmonary hypertension develops with bidirectional or right-to-left shunting, closing the defect removes the "pop-off" mechanism and can precipitate acute right heart failure and death. Management shifts to pulmonary vasodilator therapy (bosentan — Tracleer® PBS Authority Required) and referral for heart-lung transplant assessment.

Methods for Qp:Qs Measurement

Essential
Echocardiographic estimation
LVOT and RVOT VTI-based calculation. Non-invasive but operator-dependent. MBS item 55118.
Available
Cardiac MRI flow quantification
Phase-contrast MRI at aorta and main pulmonary artery. Most accurate non-invasive method. MBS item 63001 series.
Referral
Cardiac catheterisation (oximetry run)
Invasive Qp:Qs and pulmonary vascular resistance calculation. Gold standard pre-surgical decision-making.

Special Populations

🤰 Pregnancy
PFO/ASD (repaired, no residual shunt): Low risk. Vaginal delivery appropriate. Endocarditis prophylaxis not required.
Unrepaired small ASD: Generally well tolerated. Monitor for atrial arrhythmias. Increased paradoxical embolism risk during labour.
Large unrepaired shunt or Eisenmenger: HIGH RISK — maternal mortality 30–50% in Eisenmenger. Avoid pregnancy or manage at tertiary centre with obstetric anaesthesia and adult CHD team. Pulmonary vasodilator therapy (sildenafil PBS Authority Required) may be continued.
VSD (repaired, no PAH): Low risk. Vaginal delivery appropriate.
👶 Paediatrics
Spontaneous closure monitoring: Small muscular VSDs and small ASDs may close by age 2–5 years. Serial echocardiography at 6–12 month intervals. Most secundum ASDs <8 mm close spontaneously.
Surgical timing: Large VSDs causing heart failure: repair at 3–6 months of age. Primum ASD: repair at 1–2 years. Doubly-committed VSD: repair before aortic valve damage occurs.
Transition to adult care: All patients with unrepaired or repaired CHD require lifelong adult congenital heart disease (ACHD) follow-up, even if "cured." Arrhythmia risk persists post-ASD/VSD repair.
👴 Elderly
Late ASD presentation: Undiagnosed ASD may present with AF, heart failure, or stroke in the 6th–8th decade. Closure in elderly has higher procedural risk but may improve functional capacity. Individualised MDC assessment essential.
PFO closure in >60 years: Benefit less established. Cryptogenic stroke in elderly more likely due to occult AF. Prolonged cardiac monitoring essential before PFO closure.
🫘 Renal Impairment
Diuretics: Reduced efficacy in CKD; may require higher doses. Monitor potassium with ACE inhibitors and spironolactone.
Contrast use: Cardiac catheterisation and device closure: minimise iodinated contrast in eGFR <30. Pre-hydration with sodium bicarbonate or normal saline.
🫁 Hepatic Impairment
Fontan circulation: Some adult CHD patients post-Fontan may have hepatic congestion/fibrosis. Clopidogrel requires caution in severe hepatic impairment. Seek specialist advice.
🛡️ Immunocompromised
Endocarditis risk: Immunocompromised patients (transplant, chemotherapy) with residual shunts or prosthetic material are at higher risk of infective endocarditis. Dental hygiene and regular dental review are essential.

Monitoring & Follow-up

Post-device closure
Echocardiography at 24 hours, 1 month, 6 months, 12 months, then annually for 5 years. Monitor for residual shunt, device thrombosis, device erosion (rare but life-threatening — ASD devices), and pericardial effusion.
Post-surgical closure
Echocardiography at discharge, 3 months, 12 months, then as per ACHD guidelines. ECG at each visit to monitor for arrhythmias and conduction abnormalities.
Unrepaired small defect
Clinical review and echocardiography every 1–2 years in children, every 2–5 years in stable adults. Assess for development of RV/LV enlargement, pulmonary hypertension, or arrhythmias.
Eisenmenger (non-closure)
6-monthly review at specialist pulmonary hypertension centre. Annual echocardiography, 6-minute walk test, BNP/NT-proBNP, and pulse oximetry. Assessment for transplant listing when functional capacity declines.

Endocarditis Prophylaxis

ℹ️
Current Australian guidelines (CSANZ / ESC aligned): Endocarditis prophylaxis is NOT recommended for unrepaired ASD, VSD, or PFO. It IS recommended for:
  • Prior infective endocarditis (any cause)
  • Prosthetic valves or prosthetic material (including device closures — for 6 months post-implantation only)
  • Cyanotic congenital heart disease (unrepaired or with palliative shunts)
  • Repaired congenital heart disease with residual defect at or adjacent to prosthetic patch/device
When indicated: amoxicillin 50 mg/kg (max 2 g) PO 1 hour pre-dental procedure, or clindamycin 20 mg/kg (max 600 mg) if penicillin-allergic.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health
Epidemiology
Congenital heart disease rates are comparable to the general population; however, rheumatic heart disease (RHD) prevalence is markedly higher, particularly in remote NT, QLD, and WA communities. RHD-related valve disease can coexist with or mimic septal defect pathophysiology.
Diagnostic access
Echocardiographic services are limited in many remote communities. Tele-echocardiography programmes and visiting specialist cardiac clinics (e.g., NT Cardiac) are essential pathways. AIHW data show lower rates of diagnostic imaging in Aboriginal and Torres Strait Islander peoples with heart disease.
Delayed presentation
Structural barriers — distance to tertiary centres, cultural factors, and systemic racism in healthcare — contribute to later presentation with established pulmonary hypertension or Eisenmenger physiology. Earlier community-based screening and culturally safe care pathways are needed.
Surgical access
Aboriginal and Torres Strait Islander children with CHD have longer waiting times for surgery in some jurisdictions. The National Agreement on Closing the Gap (2020) includes health system accountability measures. Transfer for surgery requires culturally appropriate support — family accommodation, interpreter services, and connection to country.
Infective endocarditis
Higher rates of skin infections, dental disease, and RHD in Aboriginal and Torres Strait Islander communities increase endocarditis risk in patients with septal defects. Dental health programmes and antibiotic prophylaxis education are vital components of care.
Medication access
PBS medicines may be inaccessible due to pharmacy remoteness. Closing the Gap PBS co-payment measure reduces out-of-pocket costs. Ensure CTG eligibility is flagged in patient records. Remote Area Aboriginal Health Workers play a key role in medication adherence and monitoring.

📚 References

  1. 1. Saver JL, Carroll JD, Thaler DE, et al. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med. 2017;377(11):1022–1032. (RESPECT trial long-term follow-up)
  2. 2. Søndergaard L, Kasner SE, Rhodes JF, et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med. 2017;377(11):1033–1042. (REDUCE trial)
  3. 3. Mas JL, Derumeaux G, Guillon B, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med. 2017;377(11):1011–1021. (CLOSE trial)
  4. 4. Lee PH, Song JK, Kim JS, et al. Cryptogenic stroke and high-risk patent foramen ovale: the DEFENSE-PFO trial. J Am Coll Cardiol. 2018;71(20):2335–2342.
  5. 5. Pristipino C, Sievert H, D'Ascenzo F, et al. European position paper on the management of patients with patent foramen ovale. EuroIntervention. 2019;14(14):1480–1496.
  6. 6. Stout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA/ACC guideline for the management of adults with congenital heart disease. Circulation. 2019;139(14):e698–e800.
  7. 7. Baumgartner H, De Backer J, Babu-Narayan SV, et al. 2020 ESC guidelines for the management of adult congenital heart disease. Eur Heart J. 2021;42(6):563–645.
  8. 8. Australian Institute of Health and Welfare (AIHW). Congenital Heart Disease in Australia. Cat. no. CDK 6. Canberra: AIHW; 2019.
  9. 9. RHDAustralia (RHD Australia). The 2020 Australian guideline for prevention, diagnosis, and management of acute rheumatic fever and rheumatic heart disease. 3rd ed. Darwin: Menzies School of Health Research; 2020.
  10. 10. Australian Commission on Safety and Quality in Health Care (ACSQHC). National Safety and Quality Health Service Standards. 2nd ed. Sydney: ACSQHC; 2021.
  11. 11. Cordina R, O'Meagher S, Gould P, et al. Comparison of congenital heart disease in Indigenous and non-Indigenous Australians. Intern Med J. 2014;44(11):1113–1119.
  12. 12. Australian Government Department of Health. Closing the Gap: National Agreement. Canberra: Commonwealth of Australia; 2020.
  13. 13. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease. J Am Coll Cardiol. 2008;52(23):e143–e263.
  14. 14. Butera G, Chessa M, Carminati M. Percutaneous closure of ventricular septal defects. Cardiol Young. 2014;24(1):6–15.