Congenital Heart Disease in Adults

Mechanistic groupings (embryology drives the lesion)

• Neural crest migration failure → conotruncal defects: truncus arteriosus, tetralogy of Fallot, interrupted aortic arch, and 22q11.2 deletion syndrome (DiGeorge/velocardiofacial) — the highest-yield genetic association with outflow tract disease.
• Endocardial cushion (AV canal) failure: ostium primum ASD, inlet VSD, complete atrioventricular septal defect — the signature lesion of trisomy 21.
• Looping and laterality errors: D- and L-transposition of the great arteries, heterotaxy syndromes with associated asplenia/polysplenia.
• Flow-dependent lesions: reduced intrauterine flow across a structure arrests its growth, explaining hypoplastic left heart and the coarctation–bicuspid aortic valve–*Turner syndrome (45,X)* cluster.
• Failure of postnatal circulatory transition: PDA persists when prostaglandin-mediated ductal patency is not withdrawn — prematurity and high-altitude birth are the classic settings.

Non-modifiable risk factors

• Aneuploidy and single-gene disorders: trisomy 21, 22q11.2 deletion, Turner syndrome; Holt–Oram (TBX5) with secundum ASD plus radial ray anomaly; Noonan (RAS–MAPK) with dysplastic pulmonary valve stenosis; Williams (elastin) with supravalvular aortic stenosis; Marfan (FBN1) with aortic root dilation; Alagille (JAG1) with peripheral pulmonic stenosis.
• Family history: a first-degree relative with CHD raises recurrence risk, and the 2018 AHA/ACC Adult Congenital Heart Disease guideline supports fetal echocardiography when a parent has CHD.
• Advanced maternal age (aneuploidy risk) and male sex for coarctation and TGA.

Modifiable/exposure risk factors examiners plant in the stem

• Pregestational diabetes: hyperglycemic teratogenesis linked to TGA, VSD, and truncus arteriosus; the ADA Standards of Care target near-normal preconception A1c to reduce anomalies.
• Teratogens: alcohol (fetal alcohol syndrome with VSD/ASD), lithium (Ebstein anomaly), retinoids, valproate and other anticonvulsants, warfarin.
• Maternal infection: congenital rubella → PDA plus peripheral pulmonary artery stenosis, cataracts, deafness.
• Untreated maternal phenylketonuria and maternal obesity.

General Mechanisms of CHD Development

• Abnormal embryogenesis during weeks 3-8 of gestation affecting neural crest cell migration, endocardial cushion development, and truncus arteriosus septation
• Environmental teratogens (maternal diabetes, alcohol, rubella, anticonvulsants, warfarin) and genetic factors (chromosomal abnormalities, single-gene mutations) disrupt normal cardiogenesis
• Genetic syndromes (22q11 deletion, Marfan, Ehlers-Danlos, Down syndrome) carry high CHD prevalence

Hemodynamic Consequences by Lesion Type

• Left-to-right shunts (ASD, VSD, PDA) cause volume overload of receiving chamber, increased pulmonary blood flow, and progressive ventricular dysfunction over decades
• Right-to-left shunts (Tetralogy of Fallot, transposition) cause cyanosis, polycythemia, and paradoxical embolism risk through patent foramen ovale
• Obstructive lesions (coarctation, bicuspid aortic valve, pulmonary stenosis) create pressure gradients leading to left or right ventricular hypertrophy and eventual systolic/diastolic dysfunction
• Pulmonary vascular disease progression in chronic left-to-right shunts eventually reverses shunt direction (Eisenmenger syndrome), creating irreversible cyanosis and right heart failure

Common Adult Presentations by Lesion Type

• Atrial Septal Defect (ASD) — often asymptomatic in childhood but presents in adulthood with exertional dyspnea, palpitations, or atrial fibrillation; frequently diagnosed incidentally on echocardiography; secundum ASD most common type (70%)

• Ventricular Septal Defect (VSD) — small restrictive VSDs may be clinically silent; larger defects present with dyspnea, exercise intolerance, and signs of left heart failure; murmur characteristics depend on defect size and shunt magnitude

• Patent Ductus Arteriosus (PDA) — produces continuous "machinery" murmur; presents with wide pulse pressure, bounding pulses, and volume overload symptoms

• Tetralogy of Fallot (TOF) — cyanosis (blue baby), squatting position to increase systemic vascular resistance and decrease right-to-left shunt; clubbing, polycythemia, and stroke risk; may present with cyanotic "Tet spells" (acute hypercyanotic episodes)

• Transposition of the Great Arteries (TGA) — if not detected neonatally, presents with severe cyanosis and metabolic acidosis in infancy; adults post-Mustard/Senning repair present with systemic right ventricular dysfunction, arrhythmias

• Coarctation of the Aorta — hypertension in upper extremities with hypotension in lower extremities, reduced femoral pulses; exercise-induced headache; associated with bicuspid aortic valve, Turner syndrome, and aortic dissection risk

• Eisenmenger Syndrome — paradoxical cyanosis, dyspnea on exertion, syncope, hemoptysis; represents irreversible pulmonary hypertension and right-to-left shunt; carries high mortality risk

Important Clinical Pearls

• Many ASDs and VSDs remain undiagnosed until adulthood when atrial fibrillation or heart failure develops
• Adult CHD patients often develop "gray cyanosis" (less obvious than pediatric cyanosis) due to polycythemia compensation
• Exercise intolerance is frequently the initial presenting symptom in previously undiagnosed CHD

Clinical Assessment

• History and physical exam — document cyanosis, clubbing, squatting behavior, exercise tolerance, syncope history; auscultate for characteristic murmurs and assess femoral pulses
• Electrocardiography — may show chamber enlargement (atrial/ventricular hypertrophy), conduction abnormalities, or arrhythmias; specific patterns for ASD (right axis deviation), TOF (right ventricular hypertrophy)

Imaging Studies

• Transthoracic echocardiography (TTE) — first-line imaging; assess anatomy, chamber dimensions, wall thickness, valve function, calculate shunt ratios (Qp:Qs), and estimate pulmonary pressures
• Transesophageal echocardiography (TEE) — superior for imaging secundum ASDs, endocarditis, and thrombus; used for procedural guidance during device closure
• Chest X-ray — assess cardiac silhouette (cardiomegaly suggests volume overload), pulmonary vascularity (increased in left-to-right shunts), and bone structure (rib notching from aortic collaterals in coarctation)
• Cardiac MRI — excellent for complex anatomy, ventricular function assessment, and quantifying shunt flow; increasingly used for pre-intervention planning
• Cardiac catheterization — indicated for hemodynamic assessment (calculate pulmonary vascular resistance, measure oxygen saturation step-up), coronary evaluation in older patients, and intervention (balloon dilation, device closure)

Specific Diagnostic Criteria

• ASD diagnosis — secundum ASD requires septal defect >1 cm on imaging with Qp:Qs >1.2:1
• VSD diagnosis — spectral Doppler shows continuous left-to-right flow; size classified as restrictive (<1 cm) or non-restrictive (≥1 cm)
• Eisenmenger syndrome — diagnosis requires pulmonary vascular resistance >3 Wood units with reversed or bidirectional shunt

Important Diagnostic Consideration

• A normal electrocardiogram does NOT exclude significant CHD; many patients have preserved conduction despite structural disease
• Echocardiographic screening is indicated in any adult with unexplained dyspnea, arrhythmia, or heart murmur

Medical Management (All CHD Types)

• Endocarditis prophylaxis — antibiotics before dental/invasive procedures for high-risk lesions (complex cyanotic CHD, prosthetic valves, previous endocarditis); NOT routinely recommended for isolated ASD or simple lesions post-complete repair
• Anticoagulation — warfarin (target INR 2-3) for mechanical prosthetic valves or history of thromboembolism; consider antiplatelet therapy for cyanotic lesions to reduce stroke risk
• Beta-blockers — first-line for arrhythmia management (atrial fibrillation common in ASD); also benefit patients with ventricular dysfunction
• ACE inhibitors and diuretics — for systemic ventricular dysfunction or left heart failure; titrate carefully in cyanotic patients who may be volume-dependent

Lesion-Specific Interventions

ASD

• Observation — small (<1 cm) secundum ASDs without hemodynamic significance require only endocarditis precautions and antibiotic prophylaxis
• Percutaneous device closure — first-line for secundum ASD with adequate septal anatomy; perform if Qp:Qs >1.5:1 or signs of right ventricular volume overload
• Surgical closure — indicated for primum or sinus venosus ASDs (require surgical repair), large secundum ASDs not amenable to device closure, or ASD with associated cardiac surgery need

VSD

• Observation — small restrictive VSDs may close spontaneously (60% by age 5) or remain hemodynamically insignificant throughout life
• Percutaneous or surgical closure — indicated for non-restrictive VSDs with Qp:Qs >1.5:1, signs of left ven

Shunt-related

• Eisenmenger physiology: sustained high-flow, high-pressure pulmonary circulation remodels arterioles until PVR exceeds SVR and the shunt reverses — cyanosis, loud P2, clubbing, erythrocytosis. Differential cyanosis (cyanotic/clubbed toes, pink fingers) marks a reversed PDA shunt; reversed differential cyanosis suggests TGA with PDA.
• Paradoxical embolism: venous thrombus crosses a right-to-left shunt. Cryptogenic stroke in a young adult and brain abscess (loss of pulmonary filtration of bacteria) are both emergencies — new headache, fever, and focal deficit in a cyanotic patient means urgent neuroimaging.
• Hyperviscosity and iron deficiency: hypoxemia drives secondary erythrocytosis; iron-deficient microcytes are poorly deformable and worsen symptoms. Treat iron deficiency; the 2018 AHA/ACC ACHD guideline discourages routine phlebotomy.
• Massive hemoptysis from dilated, fragile pulmonary arteries in Eisenmenger — an emergency and a leading cause of death.

Obstructive and valvular

• Coarctation: persistent hypertension even after successful repair, recoarctation, aneurysm at the repair site, aortic dissection, and rupture of an associated berry aneurysm causing subarachnoid hemorrhage — all emergencies when acute.
• Bicuspid aortic valve: accelerated stenosis/regurgitation plus independent aortopathy requiring serial aortic imaging.

Rhythm and ventricular

• Atrial arrhythmias (intra-atrial reentrant tachycardia, flutter, fibrillation) arising from atriotomy scars and chronic atrial stretch; poorly tolerated when the systemic ventricle is a right ventricle (post-Mustard/Senning).
• Sudden cardiac death in repaired tetralogy with severe pulmonary regurgitation, RV dilation, and marked QRS prolongation.

Treatment-related

• Infective endocarditis — highest risk in unrepaired cyanotic CHD, prosthetic material within 6 months of placement, and residual shunt adjacent to a patch (AHA prophylaxis criteria).
• Device closure: embolization, erosion, residual shunt; complete heart block after perimembranous VSD device or surgical closure.
• Surgical legacies: transannular patch → free pulmonary regurgitation; baffle leak/obstruction and sinus node dysfunction after atrial switch; Fontan circulation → protein-losing enteropathy, plastic bronchitis, and Fontan-associated liver disease.
• Pregnancy in Eisenmenger or severe pulmonary hypertension carries prohibitive maternal mortality and is a contraindication.

• Fixed splitting of S2 is ASD until proven otherwise: the shunt equalizes right-sided filling across the respiratory cycle. The murmur heard is a pulmonic flow murmur, not flow through the defect. Secundum ASD gives right axis deviation with incomplete RBBB; ostium primum gives left/superior axis deviation — that axis is the single most tested discriminator.
• Smaller VSD = louder murmur: a high-velocity restrictive jet produces a harsh holosystolic murmur with thrill (maladie de Roger), whereas a large non-restrictive defect may be nearly silent. Loudness never equals severity here.
• Continuous "machinery" murmur + wide pulse pressure and bounding pulses = PDA. In an adult with Eisenmenger PDA, look for differential cyanosis — clubbed cyanotic toes with pink fingers, because the shunt enters distal to the left subclavian.
• Coarctation: measure blood pressure in all four extremities and palpate femoral pulses in every young hypertensive. Rib notching and the "3 sign" on chest film are the buzzwords; association to know is bicuspid aortic valve and Turner syndrome, and the feared complication is berry-aneurysm subarachnoid hemorrhage.
• Once Eisenmenger physiology is established, do not close the shunt. The defect is the pop-off valve for a suprasystemic right ventricle; closure precipitates RV failure and death. The best next step is referral to an adult CHD center with catheterization to assess pulmonary vascular reactivity — per the 2018 AHA/ACC ACHD guideline. Avoid abrupt systemic vasodilation, dehydration, and air in IV lines (use air filters).
• Cryptogenic nonlacunar stroke in a patient under 60 plus a positive agitated-saline bubble study should prompt evaluation for PFO closure, which the 2021 AHA/ASA secondary stroke prevention guideline supports in selected patients.
• Endocarditis prophylaxis is narrow, not universal: AHA restricts it to unrepaired cyanotic CHD, prosthetic material within 6 months, and residual defects adjacent to prosthetic patches.
• Common distractor: phlebotomy for a high hematocrit in cyanotic CHD. Erythrocytosis is appropriate compensation — correct iron deficiency instead.