- Clinical science
Acyanotic heart defects are congenital cardiac malformations that affect the atrial or ventricular walls, heart valves, or large blood vessels. Common causes include genetic defects (e.g., trisomies), maternal infections (e.g., rubella), or maternal use of drugs or alcohol during pregnancy. Acyanotic heart defects are pathophysiologically characterized by a left-to-right shunt, which causes pulmonary hypertension and right heart hypertrophy. The symptoms depend on the extent of the malformation and the resulting impairment of cardiac function. Infants may be asymptomatic or present with exercise intolerance, failure to thrive, and symptoms of heart failure. Characteristic heart murmurs are important clues for establishing the diagnosis, which is typically confirmed by visualizing the defect on echocardiography. Chest x-ray, MRI, or cardiac catheterization may also be required to determine indications for surgery and plan the procedure. Acyanotic heart defects requiring treatment are repaired via catheter procedures or surgery. Supportive medical therapy is required in cases of heart failure (e.g., diuretics, inotropic agents) or if surgery cannot be performed (e.g., prostaglandin). Common complications include arrhythmias, embolisms, and infective endocarditis, especially if treatment is delayed.
General pathophysiological processes 
- Congenital heart defects (CHDs) are caused by the disruption of the normal sequence of .
- CHDs may lead to the formation of pathological connections (shunts) between the right and left heart chambers, allowing blood to flow along the pressure gradient from high pressure to low pressure.
- The shunts are classified according to the direction of the blood flow as either left-to-right or right-to-left.
- Left-to-right shunt: oxygenated blood from the lungs is shunted back into the pulmonary circulation via an atrial septal defect (ASD), ventricular septal defect (VSD), or patent ductus arteriosus (PDA) → pulmonary hypertension and right ventricular pressure overload → right-sided heart hypertrophy (cardiomegaly on x-ray) and heart failure but no cyanosis
- Right-to-left shunt: blood flows from the right to the left heart via a shunt → deoxygenated blood entering the systemic circulation → cyanosis
Eisenmenger syndrome (can occur at any age, but usually develops during late stages of CHDs)
- Prolonged pulmonary hypertension due to a left-to-right shunt causes reactive constriction with permanent remodeling of pulmonary vessels → irreversible pulmonary hypertension
- Right ventricle hypertrophies to compensate for pulmonary hypertension → right ventricular pressure increasing and eventually exceeding left ventricular pressure → reversal of blood flow → onset of cyanosis (either at rest or during exercise), digital clubbing, and polycythemia
Pulmonary arterial hypertension (Eisenmenger syndrome) may cause untreated left-to-right shunts (acyanotic heart defects) to progress to right-to-left shunts (cyanotic defects) if right ventricular pressure exceeds left ventricular pressure.
General clinical features
For specific features, see “Clinical features” in the subsections below.
- Nonspecific findings
- Heart failure
- Differential cyanosis: cyanosis in the lower extremities if Eisenmenger syndrome occurs (seen in patients with )
General treatment considerations
- General measures: nutritional support and immunoprophylaxis
- Ductal-dependent CHDs: Infusion of prostaglandin (PGE1) to prevent closure of the ductus arteriosus (see “ ”).
- Heart failure
- Not generally recommended before procedures
- Used for 6 months after surgical correction procedures and if small defects remain following repair 
The “3 Ds” of acyanotic CHDs (in order of frequency): VSD, ASD, PDA
- The most common congenital heart defect (∼ 4/1,000 live births) 
- Occurs as an isolated heart defect or in combination with others (e.g., with , , TGA)
- Genetic syndromes
- Intrauterine infections (e.g., )
- Maternal risk factors: diabetes, obesity, smoking 
- Localization: most commonly in the membranous part of the ventricular septum (pars membranacea)
- Defect in ventricular septum → left-to-right shunt with the following consequences:
Clinical features 
- Small defects: usually asymptomatic
- Medium-sized or large defects
- Hyperdynamic precordium may be detected in hemodynamically relevant defects.
- Harsh holosystolic murmur over the left lower sternal border
- Mid-diastolic murmur over cardiac apex
- Systolic thrill
- Loud pulmonic S2 (if pulmonary hypertension develops)
Echocardiography (confirmatory test)
- To assess defect size and shunt volume
- Doppler ultrasound findings of pathological left-to-right blood flow can help diagnose minor ventricular defects.
- Small defects: normal ECG findings
Medium-sized or large defects
- Signs of LV hypertrophy (due to volume loading): ↑ QRS amplitude, left axis deviation, left atrial enlargement
- Signs of RV hypertrophy (due to pulmonary hypertension or obstruction of the pulmonary outflow tract): vertical or right axis deviation, P pulmonale, PR prolongation, complete or incomplete right bundle branch block
- Chest x-ray
- Small defects often heal spontaneously and rarely require surgical interventions (follow-up echocardiography is recommended)
Symptomatic and large defects
- See “General treatment considerations” in “Overview” above.
- Surgical (patch) repair
- If Eisenmenger syndrome has occurred: heart-lung transplant or lung transplant with concurrent VSD repair
- Second most common CHD (∼ 2/1,000 live births)
- Sex: ♀ > ♂
- Holt-Oram syndrome (hand-heart syndrome)
- Impaired growth or excessive resorption of the atrial septa in utero leads to atrial septal defects (absent atrial septa tissue).
- Typically a low-pressure, low-volume, minor (therefore, patients are asymptomatic)
- ASD → oxygenated blood shunting from LA to RA → ↑ O2 saturation in the RA → ↑ O2 saturation in RV and pulmonary artery
- In more severe defects, the shunts may lead to , , and/or .
- Depend on defect size and shunt volume
- Small defects: usually asymptomatic
Medium-sized to large defects
- Symptoms can vary from asymptomatic to heart failure.
- ASDs typically manifest with advancing age. 
- Systolic ejection murmur over the second left ICS sternal border
- Widely split second heart sound (S2) over the second left ICS, which is fixed (does not change with respiration )
- Soft mid-diastolic murmur over the lower left sternal border
- See “General clinical features” above.
- Echocardiography (confirmatory test): interatrial communication, best visualized in the apical four-chamber and subcostal views
- ECG: signs of RV hypertrophy (vertical or right axis deviation, P pulmonale, PR prolongation, complete or incomplete right bundle branch block)
- Enlarged right atrium, ventricle, and pulmonary arch
- Enhanced pulmonary vasculature
- In children with ASD, spontaneous closure may occur.
- Indicated in symptomatic children with a significant left-to-right shunt
- Surgical or via percutaneous transcatheter procedure
- ↑ risk of ischemic ) (: small blood portions from inferior vena cava bypass pulmonary circulation → direct emptying into left atrium → paradoxial embolism and stroke in the case of thromboembolism
- Heart failure
- Prevalence: 25–30% of the general population
- Associated with Loeys-Dietz syndrome
- Failure of the atrial septum primum to fuse with the septum secundum following birth → persistence of foramen ovale; → mild
- A shunt reversal may be induced by certain maneuvers that increase right atrial pressure (e.g., , coughing).
ASD = Septal tissue Deficiency. PFO = enough tissue, but Problems with Fusion.
- Affected individuals are usually asymptomatic until complications occur (see below).
- Often an incidental finding
- If ischemic stroke occurs
- Contrast echocardiography (best initial and confirmatory test): to evaluate defect size and shunt volume
- Transesophageal echocardiography: if contrast echocardiography findings are negative
- Asymptomatic PFO: Treatment is not usually required.
Ischemic infarction in patients with confirmed PFO
- Antiplatelet agents or anticoagulation
- Surgical or percutaneous closure of the defect
- Systemic embolisms (e.g., renal infarction)
- Failure of the ductus arteriosus to completely close postnatally
- Incidence: ∼ 5/10,000 full-term births
- In premature infants: 20–60% 
- Sex: ♀ > ♂ (2:1) 
- Isolated heart defect in 90% of cases
- Maternal exposure during pregnancy
- Respiratory distress syndrome
- Trisomies (e.g., Down syndrome)
- Ductus arteriosus enables the underdeveloped lungs to be bypassed by the fetal circulation (normal right-to-left shunt) and remains patent in utero via PGE and low O2 tension.
- After birth, pulmonary vascular resistance decreases and thus allows for the reversal of the shunt from right-to-left to left-to-right.
- Failure of the ductus arteriosus to close after birth → persistent communication between the aorta and the pulmonary artery → left-to-right shunt → volume overload of the pulmonary vessels → continuous RV (and/or LV) strain → heart failure (see also “Overview” above)
- may occur with shunt reversal and manifest with .
- Small PDA: asymptomatic with normal findings on physical examination
- Nonspecific symptoms (e.g., failure to thrive); and symptoms of heart failure in infancy (see the “Overview” above)
- Heaving, laterally displaced apical impulse
- Bounding peripheral pulses, wide pulse pressure 
- Machinery murmur: loud continuous murmur heard best in the left infraclavicular region and loudest at S2
PDA comes with Prolonged Deafening Auscultation findings.
- Echocardiography (confirmatory test)
- Chest x-ray
- Cardiac catheterization and angiography: only necessary prior to repair or in more complex CHDs
- Observation: regular heart and pulmonary vasculature evaluation in patients with small PDAs and no evidence of left-sided heart volume overload
Elective ductal closure
Indications for closure
- Symptomatic PDAs
- Left heart enlargement; or mild to moderate
- Pharmacological closure (in premature infants): infusion of indomethacin or ibuprofen
- In infants > 5 kg: percutaneous catheter occlusion or surgical ligation
- Indications for closure
- Administer prostaglandin (PGE1) to keep the PDA open if needed for survival (e.g., in , , ).
- Narrowing of the aorta at the aortic isthmus, which is a distal part of the aortic arch, close to the ductus arteriosus (juxtaductal) and left subclavian artery
- Rarely, the coarctation is located in the thoracic or abdominal aorta
- Prevalence: 4/10,000 live births
- Sex: ♂ > ♀
- The exact etiology is unclear
- Two etiological theories have been developed.
- Associated with (in 5–15% of female patients with coarctation) 
- Often accompanied by a bicuspid aortic valve , VSD, and/or PDA
- Acquired: e.g., atherosclerosis , severe
- Genetic defects and/or intrauterine ischemia → medial thickening and intimal hyperplasia forming a ridge encircling the aortic lumen → narrowing of the aorta → ↑ flow proximal to the narrowing and ↓ flow distal to the narrowing
- In cases of discrete stenosis: Left ventricular outflow obstruction → myocardial hypertrophy and increased collateral blood flow (e.g., intercostal vessels, scapular vessels).
- In long segment stenosis, compensatory mechanisms do not develop → closure of PDA after birth → left ventricular pressure and volume overload → hypoperfusion of organs and extremities distal to the stenosis 
Clinical features 
- Asymptomatic as long as PDA is present or if aortic narrowing is mild
- : cyanosis of the lower extremities (when the left subclavian artery outflow is involved, cyanosis might also be seen in the left arm)
- Brachial-femoral delay: weak femoral pulses
- ↑ Blood pressure (BP) in upper extremities and ↓ BP in lower extremities
- Cold feet and lower-extremity claudication upon physical exertion
- Systolic ejection murmur over left posterior hemithorax and/or continuous murmur below left clavicula and between the shoulder blades
- Strong apical impulse displaced to the left
- Headache, epistaxis, tinnitus
- In severe stenosis: See “Nonspecific findings” and “Heart failure” in “Overview” above.
- In severe stenosis: shock and multiorgan failure when ductus arteriosus closes
Blood pressure measurements
- Best initial test
- BP measurements for upper and lower extremities to check for brachial-femoral delay
- Pulse oximetry: ↓ SpO2
- Doppler echocardiography (confirmatory test): location and extent of stenosis; detection of concurrent anomalies (VSD, PDA, bicuspid aortic valve)
- Cardiomegaly and ↑ pulmonary vascular markings
- Figure of 3 sign: the result of an hourglass-like narrowing of the aorta caused by pre- and postdilatation of the aorta with an indentation at the site of coarctation
- Rib notching: a radiographic sign caused by collateral circulation between the internal thoracic and intercostal arteries.
MRI or CT
- In complicated cases and in adults
- To determine the length of coarctation and for intervention planning
- Genetic testing: for
- Initial management: infusion of prostaglandin (PGE1)
- Surgical correction; or balloon angioplasty: for most patients < 5 years of age. Older patients may have a transcatheter intervention with stent placement.
- Follow-up and monitor for restenosis, , and .
- Defect of atrioventricular valves (i.e., mitral and tricuspid valves) as well as the atrial and/or ventricular septum
- Strongly associated with 
- Association with maternal diabetes and obesity has been shown in some studies. 
- Complete form (ASD and VSD) → atrial and ventricular left-to-right shunt → excessive pulmonary blood flow and biventricular volume overload → and heart failure
- Partial form (ASD only) → atrial left-to-right shunt → symptoms that may remain minimal until adulthood
- In both forms: abnormal AV valve → AV valve regurgitation → in utero heart failure (nonimmune hydrops fetalis)
Clinical features 
- Complete form: See “Nonspecific findings” and “Heart failure” in “Overview” above.
- Partial form: See “Clinical features” in “ “ above.
- Antenatal echocardiography: findings of endocardial cushion defect in first trimester → screening for
- Echocardiography (confirmatory test): to assess defect size, shunt volume, and global cardiac function
- ECG: left axis deviation due to LVH
- Chest x-ray
- Relatively common in the general population (7–12% of all CHDs) 
- Usually congenital (rarely acquired )
- Pulmonary valve stenosis → right ventricular outflow obstruction → pressure overload → right ventricular hypertrophy
- Depending on the grade of stenosis, symptoms of heart failure may occur.
- Systolic murmur heard best over the second left ICS at the sternal border
- S2 wide splitting
- Echocardiography (confirmatory test): to assess the severity of stenosis
- Chest x-ray: Findings in adults with isolated pulmonary stenosis show a prominent pulmonary artery segment.
Transcatheter dilatation of the pulmonary valve
- Indication: prestenotic to poststenotic pressure gradient > 50 mm Hg
- Technique: balloon pulmonary valvuloplasty
- Surgery: commissurotomy if balloon dilatation is not possible