Cardiovascular · PANCE / PANRE

Atrial Septal Defect (ASD)

Opening in the interatrial septum producing left-to-right shunt, fixed split S2, and risk of paradoxical embolism.

Also known as: ASD, atrial septal defect, secundum ASD, primum ASD, sinus venosus defect

Overview

Congenital communication between the left and right atria allowing left-to-right shunting of oxygenated blood, with progressive right heart volume overload. Anatomical subtypes include ostium secundum (most common, ~75%), ostium primum (associated with AV canal defects and Down syndrome), sinus venosus (often with anomalous pulmonary venous drainage), and unroofed coronary sinus.

Epidemiology

Accounts for ~10% of congenital heart disease; female predominance ~2:1. Most common congenital heart defect diagnosed in adulthood. Patent foramen ovale (a flap-valve, not a true ASD) is present in 25-30% of the general population and is implicated in cryptogenic stroke.

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Risk factors

  • Family history of congenital heart disease
  • Down syndrome (primum ASD/AV canal defect)
  • Holt-Oram syndrome (autosomal dominant TBX5 mutation; ASD + upper limb anomalies)
  • Maternal exposures: rubella, alcohol, smoking
  • Female sex

Pathophysiology

Left atrial pressure exceeds right atrial pressure in normal physiology, producing left-to-right shunting through the defect with right-sided volume overload, RA and RV dilation, and increased pulmonary blood flow. Compliance of the RV (greater than LV in adults) further drives shunt magnitude. Over decades, sustained pulmonary overcirculation can lead to pulmonary vascular remodeling and shunt reversal (Eisenmenger syndrome), though this is now uncommon with modern care. PFOs allow transient right-to-left shunting during Valsalva or coughing, enabling paradoxical embolism.

Clinical presentation

Symptoms

  • Often asymptomatic in childhood; diagnosed in adulthood after decades of right heart volume overload
  • Exertional dyspnea, fatigue, palpitations (atrial arrhythmias)
  • Recurrent respiratory infections in larger defects
  • Cryptogenic stroke or TIA (especially PFO with paradoxical embolism)
  • Migraine with aura — associated with PFO, though closure does not consistently improve symptoms

Signs / physical exam

  • Wide and fixed splitting of S2 — pathognomonic (the RV ejection time stays prolonged regardless of respiration because the RA volume is augmented from both venous return and the shunt)
  • Soft mid-systolic flow murmur at upper left sternal border (pulmonic outflow)
  • Mid-diastolic rumble at lower left sternal border in large shunts (increased tricuspid flow)
  • Right ventricular heave at the lower left sternal border
  • Loud P2 if pulmonary hypertension develops

Classic findings

Wide and fixed split S2 with pulmonic flow murmur in an otherwise asymptomatic adult.

Differential diagnosis

  • VSD — Holosystolic murmur at LLSB, no fixed split S2; pulmonary congestion and HF in infancy if large
  • PDA — Continuous machinery murmur, wide pulse pressure, bounding pulses
  • Innocent flow murmur — Soft, mid-systolic, no fixed split, no chamber enlargement on echo
  • Anomalous pulmonary venous return (partial or total) — Often coexists with sinus venosus ASD; right heart dilation out of proportion to ASD size
  • Pulmonic stenosis — Systolic ejection murmur at ULSB, click, no fixed split; isolated lesion on echo
  • Pulmonary embolism (in adult with new RV dilation) — Acute onset, hypoxia, D-dimer elevation, CTPA confirms

Diagnostic workup

Diagnostic criteria

Hemodynamically significant ASD warranting closure: right heart enlargement on imaging and Qp/Qs ≥1.5, OR documented paradoxical embolism, OR platypnea-orthodeoxia. Closure is generally contraindicated if pulmonary vascular resistance is severely elevated and irreversible.

Labs

  • Basic labs typically unremarkable
  • BNP may be elevated if symptomatic HF

Imaging

  • Transthoracic echocardiography with agitated saline (bubble study) and color Doppler — visualizes defect, direction and magnitude of shunt, RA/RV size, RV function, and estimates pulmonary pressures
  • Transesophageal echocardiography for better characterization of sinus venosus and sinus coronarius defects and to evaluate suitability for percutaneous closure
  • ECG: incomplete or complete right bundle branch block (RBBB), right axis deviation in secundum ASD; LEFT axis deviation is characteristic of primum ASD due to abnormal AV node anatomy; atrial arrhythmias
  • CXR: cardiomegaly with prominent RA and RV, increased pulmonary vascular markings, prominent main pulmonary artery
  • Cardiac MRI or CT: defining anatomy, anomalous pulmonary venous return, Qp/Qs quantification
  • Cardiac catheterization with shunt run (Qp/Qs) and pulmonary vascular resistance assessment if pulmonary hypertension or closure decision is uncertain

Diagnostic algorithm

ASD SubtypeFrequencyLocationECG AxisClosure Strategy
Secundum~75%Mid-septum (fossa ovalis)Right axis deviation, RBBB patternTranscatheter device (preferred) or surgical
Primum~15-20%Inferior septum, near AV valvesLEFT axis deviationSurgical (often with AV valve repair)
Sinus venosus~5-10%Superior or inferior septum near vena cavaeVariable, often abnormal P-wave axisSurgical (often with PAPVR repair)
Coronary sinus<1%Unroofed coronary sinusVariableSurgical
Anatomic subtypes of ASD and key distinguishing features.

Treatment

First-line

  • Secundum ASD: percutaneous transcatheter device closure (e.g., Amplatzer septal occluder) is the preferred approach when anatomy is suitable (adequate rims, defect <38 mm)
  • Primum, sinus venosus, and unroofed coronary sinus defects, as well as secundum defects with inadequate rims: surgical patch closure
  • Dual antiplatelet therapy (aspirin + clopidogrel) for 6 months following device closure, then aspirin alone for at least 6 additional months

Second-line / adjunct

  • Symptom-directed management of atrial arrhythmias (rate or rhythm control, anticoagulation per CHA2DS2-VASc)
  • PFO closure in patients <60 with cryptogenic stroke and high-risk features (atrial septal aneurysm or large shunt) — supported by RESPECT, CLOSE, REDUCE trials
  • Diuretics and pulmonary vasodilators (sildenafil, bosentan) for ASDs with Eisenmenger physiology
  • Endocarditis prophylaxis NOT routinely required for isolated ASD per AHA guidelines (only for first 6 months after device closure or repair, or if a residual defect remains adjacent to prosthetic material)

Complications

  • Atrial arrhythmias (atrial fibrillation, atrial flutter)
  • Pulmonary hypertension and Eisenmenger syndrome
  • Right heart failure
  • Paradoxical embolism: stroke, TIA, peripheral arterial embolism
  • Endocarditis (rare in isolated ASD)
  • Platypnea-orthodeoxia syndrome: dyspnea and hypoxemia upright that improves supine, due to positional right-to-left shunting

PANCE pearls

  • Wide and fixed split S2 is the auscultatory hallmark — does NOT vary with respiration.
  • Primum ASDs (associated with Down syndrome and AV canal defects) classically have LEFT axis deviation on ECG, while secundum ASDs cause RIGHT axis deviation.
  • Holt-Oram syndrome: ASD + upper limb defects (especially thumb anomalies) — TBX5 mutation, autosomal dominant.
  • PFO closure for cryptogenic stroke is supported in patients <60 with high-risk features (large shunt or atrial septal aneurysm). Closure is not routinely indicated for migraine alone.
  • ASD frequently presents in middle-aged women with new-onset atrial fibrillation or unexplained right heart enlargement — keep on the differential.

References

  • AHA/ACC 2018 — 2018 AHA/ACC Guideline for the Management of Adults with Congenital Heart Disease (Stout et al., Circulation 2019)
  • RESPECT Trial — Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke (Saver et al., NEJM 2017)
  • CLOSE Trial — PFO Closure or Anticoagulants versus Antiplatelet Therapy after Stroke (Mas et al., NEJM 2017)
  • REDUCE Trial — PFO Closure or Antiplatelet Therapy for Cryptogenic Stroke (Søndergaard et al., NEJM 2017)

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