A. Introduction

1. Increasing numbers of adults in USA with congenital cardiac defects
2. Prevalence in USA is ~1 million
3. May be divided into acyanotic and cyanotic conditions
4. Acyanotic Conditions [9]
   1. Atrial Septal Defect (ASD)
   2. Ventricular Septal Defect (VSD)
   3. Patent Ductus Arteriosus (PDA)
   4. Aortic Stenosis
   5. Pulmonic Stenosis (PS)
   6. Aortic Coarctation
   7. Anomalous coronary arteries - may be associated with sudden cardiac death [4]
5. Cyanotic Conditions [10]
   1. Tetrology of Fallot
   2. Transposition of the Great Arteries
   3. Ebstein's Anomaly
   4. Eisenmenger's Syndrome
   5. Double Outlet Right Ventricle
6. Common findings in Congenital Heart Disease
   1. Hypoxia causes polycythemia
   2. Hepatomegaly due to congestive heart failure
   3. Symptoms of congestive heart failure
   4. Pulmonary hypertension (P-HTN, often after surgery for congenital heart disease)
7. Diagnostic Evaluation
   1. Electrocardiogram (ECG), echocardiogram, cardiac catheterization
   2. Most cardiac catheterization is guided by fluoroscopy
   3. Magnetic resonance imaging (MRI) guided catheterization is feasible in congenital disease [25]
8. Tri-iodothyronine (T3) Treatment and Heart Surgery [11]
   1. Treatment with T3 for children after cardiopulmonary bypass surgery evaluated
   2. Treatment on day of surgery, then up to 12 days after
   3. Improves myocardial function without adverse events
   4. Reduces need for postoperative intensive care
   5. Should be considered in children undergoing cardiopulmonary bypass operations
9. Some reports of increased risk of congenital heart disease with serotonin selective reuptake inhibitors (SSRI) have not been verified [31,32]
10. Congenital heart disease associated with abnormal brain development in newborns [5]

B. Ventricular Septal Defect (VSD) [20]
[Figure] "Blood Flow in VSD"

1. Most common type of congenital cardiac defect in infants and children
   1. About 20% of all cases of congenital heart defects
   2. About 10% of defects diagnosed in adults
   3. Up to 40% of cases of VSD close spontaneously
   4. Majority of closures occur by age 10
2. Connection between Right Ventrical (RV) and Left Ventrical (LV)
   1. 75% of VSD located in membranous portion of intraventricular septum
   2. 15% found in muscular or trabecular portion of septum
   3. Canal or inlet defects 8%, typically large, associated with Down Syndrome
   4. 5% just below the aortic valve (leading to aortic regurgitation)
   5. 5% near the junction of mitral and tricuspid valves
   6. 35% associated with ASD, 22% with PDA, <5% with pulmonary stenosis
3. Physiology
   1. Determined primarily by size and not by location of VSD
   2. LV blood is shunted into the RV initially
   3. Elevated right sided pressures and increased pulmonary blood flow
   4. Left Atrial (LA) and LV volume overload with dilation
   5. Increased risk of infective endocarditis
   6. Increased association with aortic insufficiency (AI), particularly in young men
   7. If PS and/or pulmonary HTN present, RV to LV shut can occur
4. Diagnosis
   1. Holosystolic murmer only heard with moderate or large defects
   2. Murmer loudest at lower left sternal border
   3. Echocardiography with Doppler flow is often diagnostic
   4. On ECG, high voltage T waves often seen
   5. Pulmonary pressures and blood flow should be assessed
   6. Small defects are often associated with little if any abnormalities
   7. In adults, presents as PS, pulmonary hypertension, or AR
   8. Prolonged VSD can lead to Eisenmenger Syndrome (usually by age 20-30) [7]
   9. Thus, pulmonary vascular disease must be monitored
   10. Pulmonary vascular resistance >70% of systemic resistance is very severe
   11. Frequent echocardiographic monitoring is required
5. Moderate or large anomalies should be repaired early in life
6. Pulmonary Hypertension (P-HTN) [15]
   1. Frequent complication following repair of septal defects (ventricular and some atrial)
   2. Inhaled nitric oxide after surgery for septal defects can lessen risk of P-HTN
   3. Inhaled nitric oxide also reduces postoperative course with no side effects
7. Ventriculoseptal defect repairs should be followed by lifelong endocarditis prophylaxis

C. Atrial Septal Defect (ASD) [9]
[Figure] "Blood Flow in ASD"

1. Epidemiology
   1. Overall, approximately 11% of congenital cardiac defects
   2. Accounts for about 30% of defects in adults
   3. About 70% of cases are found in women
   4. May present in adulthood
   5. Small ASD's require 10-20 years to become symptomatic
2. Types
   1. Ostium primum (~15%) - defect in lower part of atrial septum
   2. Ostium secundum (~75%)- defect in fossa ovalis
   3. Sinus venosus (~10%) - defect in upper part of atrial septum
3. Pathophysiology
   1. Diastolic overload RV
   2. Initial hypervolemia causes RV dilation leading to cardiomyopathy
   3. Many patients live into adulthood and develop severe symptoms at age over 40 years
   4. Long term ASD can lead to development of Eisenmenger Syndrome (see below) [7]
4. Symptoms and Signs
   1. May present with shortness of breath or dyspnea on exertion
   2. Peripheral edema or atrial arrhythmias
   3. Fixed splitting of S2 is common
   4. May have systolic ejection murmer (SEM), second intercostal space
   5. Atrial flutter and fibrillation are not uncommon, and are present in >60% after age 40
   6. These arrhythmias also occur after surgical repair, associated with P-HTN [8]
   7. Right to left shunt (Eisenmenger's Syndrome) can develop from P-HTN
5. Diagnosis
   1. Transthoracic or transesophageal echocardiography are generally confirmatory
   2. ECG shows incomplete right bundle branch block (RBBB)
   3. Right axis deviation, long QRS, delayed deflection, tripartite waves
   4. Primary atrioventricular block may occur
6. Indications for Treatment [1]
   1. Hemodynamically unimportant ASD (Qp/Qs < 1.5) do not generally need repair
   2. Small ASD with parodoxical emboli in patients with cryptogenic stroke should be repaired
   3. Large ASD or ASD with symptoms should generally be repaired
   4. Asymptomatic patients should have closure only with high risk of long term complications
7. Surgical Repair versus Medical Therapy [23]
   1. Key is to repair the defect before P-HTN and RV damage occurs
   2. New catheter-deployed umbrella devices can be used for most ASD's and are safe
   3. Surgery in adults >40 years of age shown to reduce mortality and complications [8]
   4. Earlier age and lower pulmonary pressures at surgery is associated with lower incidence of post-surgical atrial arrhythmias [8]
   5. No apparent reduction of incidence of atrial arrhythmias or their complications
   6. Inhaled nitric oxide after surgery for ASD can lessen risk of P-HTN [15]
   7. Does not require antibiotic prophylaxis because interatrial gradients are low

D. Pulmonic Stenosis (PS)

1. Approximately 10% of congenital defects
   1. May be associated with other abnormalities, especially VSD
   2. 90% of cases due to obstruction of RV outflow
2. Obstructive lesion causes increased RV afterload, leading to RVH
   1. Normal pulmonary valve orifice is 2.0cm2/m2 body area
   2. Normally no pressure gradient across the pulmonary valve
   3. Mild stenosis is >1.0cm2/m2
   4. Moderate stenosis is 0.5-1.0cm2/m2 or transvalvular gradient 75-100mmHg
   5. Severe stenosis is <0.5cm2/m2 or >80mm Hg or RV systolic pressure >100mg Hg
   6. Increased RV pressures, particularly with VSD, can lead to Eisenmenger Syndrome [7]
3. Diagnosis
   1. RV impulse may be palpated at left sternal border
   2. Second heart sound is widely split (A2-P2)
   3. ECG shows increased voltages, right axis deviation
   4. Thus, R>>S in V1; R<S in V6
   5. Echocardiogram used to monitor pressures, paradoxical septal motion
4. Peripheral pulmonic stenosis may be associated with maternal rubella infection
5. Treatment
   1. Percutaneous balloon valvuloplasty is first line treatment for children
   2. For patients who present as adolescents or adults, balloon valvuloplasty highly effective
6. Endocarditis prophylaxis is required

E. Patent Ductus Arteriosis (PDA)
[Figure] "Blood Flow in PDA"

1. Epidemiology
   1. PDA accounts for ~10% of congenital cardiac defects
   2. Increased incidence in pregnancies complicated by perinatal hypoxia
   3. Also increased in meternal rubella, premature infants, and high altitude births
2. Normal ductus arteriosis
   1. Connects descending aorta to left pulmonary artery
   2. Result is that blood bypasses nonfunctioning fetal lungs
   3. During first two months of life becomes ligamentum arteriosum (a fibrous cord)
   4. The ductus normally closes in response to decreased prostaglandins (PGE1) at birth
3. Patent Ductus
   1. Failure of ductus to involute
   2. Blood shunts from aorta to the pulmonary artery (left to right shunt)
   3. Causes pressure and volume overload of pulmonary artery
   4. Fatigue, dyspnea, or palpitations may develop during childhood or adulthood
   5. Eventually causes "high output" cardiac failure if left alone (~30%)
   6. In addition, LA and LV overload may ensue due to Eisenmenger Syndrome
   7. Right and/or Left sided congestive heart failure may occur
4. Pharmacologic Manipulation
   1. Maintain open ductus in some forms of congenital heart disease with PGE1 (alprostadil)
   2. Indomethacin and other prostaglandin inhibitors induces PDA closure in >65%
   3. Ibuprofen is better tolerated than and as effective as indomethacin in closing PDA [12]
   4. Three doses of ibuprofen given within 3 hours of birth in preterm infants reduces incidence of PDA from ~75% (placebo) to near 0% (ibuprofen)
   5. Prophylactic ibuprofen in premature infants (<28-31 weeks) incresases PDA closure and the need for surgical ligation but not mortality [27,28]
5. Repair of PDA [1]
   1. Repair of PDA recommended prior to development of pulmonary vascular disease
   2. Clinically detectable PDA should generally be closed unless irreversible P-HTN is present
   3. Closure reduces risk of infectious endocarditis
   4. Transcatheter devices are now available and result in ~85% PDA closure rates
   5. Surgical closure by ductal ligation or division usually for ducts >8mm

F. Persistent Patent Foramen Ovale (PFO) [33]

1. The foramen ovale is an opening between the right (R) and left (L) atria
2. During development in utero, provides a means of bypassing nonfunctional lungs
3. Normally, after birth, pressure in LA rises and the foramen ovale closes
   1. This closure prevents left-to-right (L to R) shunting of circulation
   2. The initial closure is called septum primum and is simply a pressure induced seal
   3. Over 1 year, fibrous adhesions form on the primary septum forming the septum secundum
4. Persistent PFO
   1. In some persons, the foramen ovale does not seal properly
   2. This leads to persistence of a PFO
   3. LA pressures greater than those in the right atrium (RA) maintain closed foramen
   4. Under conditions of elevated RA pressures, the foramen may open
   5. PFO may be responsible for "orthodexia", a reduction in O2 saturation from recumbent to erect position [30]
5. Complications of Persistent PFO
   1. Eisenmenger syndrome (R to L shunts with congestive heart failure) [33]
   2. Stroke due to paradoxical embolism: venous embolism through R to L shunt leads to arterial stroke [29]
   3. PFO is a risk for stroke in both younger (4.7X risk) and older (2.9X risk) patients [2]
   4. PFO diameter is an independent risk factor for all ischemic events, especially strokes [14]
   5. ~55% of patients with cryptogenic embolic stroke have PFO, versus 27% PFO overall
   6. PFO with atrial septal aneurysm is a high risk for cerebrovascular events [3]
   7. In PFO with atrial septal aneurysm, anticoagulation with agents stronger than aspirin should be considered [3]
   8. In young patients with PFO and stroke, warfarin for 3-6 months (then aspirin) in addition to closure of the PFO is recommended [29]
   9. Associated with migraine with aura, particularly when R to L shunt present [16]
   10. Increased risk of high-altitude pulmonary edema (HAPE, including "mountain sickness") and altitude-associated arterial hypoxemia in persons with persistent PFO [6]
   11. Scuba diving with PFO increases risk for decompression illness and ishemic brain lesions [17]
6. Diagnosis [33]
   1. Echocardiographic evidence on Doppler blood flow of continuous blood flow in PA bifurcation
   2. Right ventricular dilation with right atrial or biatrial dilation
   3. Cardiac catheterization is definitive
   4. Assessment of oxygen saturation across chambers of heart confirms diagnosis
7. Treatment
   1. Indicated for patients with any symptoms of PFO
   2. Also indicated for PFO and any evidence of cardiac dysfunction likely related to PFO
   3. Long term medical therapy with antiplatelet agents or anticoagulation has been used
   4. Transcatheter closure of PFO is now safe and very effective
   5. Transcatheter closure of PFO may prevent cryptogenic embolic strokes [24]

G. Aortic Stenosis

1. Epidemiology
   1. Bicuspid aortic valve is most common underlying abnormality
   2. Occurs in ~2.5% of population
   3. About 80% of cases are found in men
2. Abnormalities of medial layer of aorta are often found
3. Left alone, usually presents with syncope, angina or heart failure
4. Patients have LV hypertrophy and weak/delayed carotid pressures
5. Early Myocardial Infarction
   1. May occur due to LVH with poor coronary perfusion
   2. This can occur with or without obstructive coronary artery disease
6. Endocarditis prophylaxis is required following correction (highest rate of all CHD)
7. Repair [1]
   1. Presence of symptoms
   2. Severe aortic stenosis should generally be repaired prior to pregnancy
   3. Bicuspid aortic valve can be treated with valvuloplasty in age <30 and if valve not calcified
   4. Prophylactic repair for proximal aortic dilation >5.5cm recommended over waiting

H. Coarctation of Aorta (COA) [1]

1. Constriction in aorta due to congenitally developed tissue septum
   1. Can occur anywhere along thoracic aorta
   2. Most commonly occurs at ligamentum arteriosum (distal to left subclavian artery)
   3. Most common types lead to unequal pulses and hypertension in the arms
2. Hypoperfusion may occur in any branch of the aorta
   1. Carotid occlusions can lead to syncope
   2. Extensive arterial collaterals develop over time
   3. Hypertension in areas proximal to coarctation occurs
3. Symptoms and Signs
   1. Systolic hypertension, restricted to upper extremity (L > R blood pressure)
   2. Diastolic pressures are equal
   3. Systolic murmer may be heard in the back (due to collateral blood flow)
   4. Reduced femoral pulses - some patients will have underdeveloped lower limbs
   5. Left ventricular hypertrophy (LVH) develops early on
   6. LVH may lead to chest pain, early ischemia
4. ECG Changes
   1. Left Axis Deviation with high voltage QRS due to LVH
   2. ST-T changes consistent with abnormal repolarization
   3. V6 T wave inversion
5. Chest radiograph
   1. Shows rib notching (due to collateral vessels)
   2. Prominent vasculature
6. Repair
   1. Graft bypass surgery for patients with transcoarctation pressure gradient >30mm Hg
   2. 90% of patients who have correction in childhood have normal blood pressure at 5 years
   3. Dilation of segment - may cause aneurysm or other problems
7. Endocarditis prophylaxis is required following correction

I. Tetralogy of Fallot [10]

1. Most common cause of cyanosis in persons <1 year of age
2. Components
   1. Large VSD leads to systolic overload of RV leading to RVH
   2. Pulmonic stenosis
   3. Dextroposition of the aorta
   4. Right Ventricular Hypertrophy (RVH)
   5. Optional: right aortic arch, ASD, coronary abnormalities occur in 10-25% of cases as well
3. Symptoms are related to RV outflow obstruction
   1. Significant right to left shunting
   2. Reduced pulmonary blood flow
   3. Dyspnea, cyanosis and digital clubbing are common
   4. Polycythemia is prominent
   5. Children frequently squat to increase RA filling and pulmonary blood flow
4. Diagnosis
   1. Echocardiography with can be used to quantitate shunting
   2. ECGH shows right axis deviation and RVH
   3. S>R after V2 or V3 (due to RVH)
   4. Cardiac catheterization confims diagnosis and can be used to quantitate
   5. Magnetic resonance angiography may also be used
5. Surgical Correction
   1. Required or the condition is fatal
   2. Performed when very young has <3% mortality
   3. In adults, mortality is 2.5-8.5%
   4. Surgery greatly improves survival, but patients still have reduced expected lifespan
   5. Atrial arrhythmias and right bundle branch block common after surgery
   6. Increased risk over time for atrial fibrillation, atrial flutter, ventricular tachycardia
   7. Severe pulmonary regurgitation can occur, and valve replacement may be required
   8. Increased risk of sudden cardiac death, probably due to cardiac anomalies
6. Endocarditis prophylaxis following repair is recommended
7. Late Risk Factors [13]
   1. Ventricular arrhythmia and sudden cardiac death
   2. Heart failure
   3. Pulmonary valve abnormalities and P-HTN
   4. Patients with TOF and P-HTN have high risk of ventricular arryhtmias
   5. Preservation or restoration of pulmonary valve function may reduce risk

J. Eisenmenger Syndrome [7]

1. Components of Syndrome
   1. Elevated pulmonary vascular resistance
   2. Right to left shunting of blood through systemic to pulmonary circulation
   3. Secondary changes related to hypoxemia and overloaded heart failure
2. Causes
   1. Ventricular Septal Defect
   2. Atrial Septal Defect
   3. Tetrology of Fallot
   4. Patent Ductus Arteriosus
   5. Increased pulmonary vascular resistance with reversal of blood flow
   6. Eisenmenger syndrome can also occur in adults due to chronic lung disease
3. Progression of Pulmonary Vascular Disease
   1. Medial hypertrophy of pulmonary arterioles
   2. Intimal proliferation and fibrosis
   3. Occlusion of capillaries and small arterioles
   4. Plexiform lesions and necrotizing arteritis are late stage and irreversible
4. Symptoms
   1. Cyanosis appears as right to left shunting occurs
   2. Shortness of breath and/or dyspnea on exertion
   3. Digital clubbing
   4. Palpitations, commonly with atrial fibrillation
   5. Prominant V waves seen if tricuspid disease is present
   6. Arterial pulses are weak (small volume)
   7. Murmers, especially associated with underlying conditions, disappear
5. Complications
   1. Erythrocytosis (polycythemia) - may be associated with hyperviscosity
   2. Hyperviscosity syndrome - retinal effects, paresthesias, headaches
   3. Thromboembolic Events
   4. Others: hemoptysis, gout, cholelithiasis, hypertrophic cardiomyopathy (especially RV)
   5. Arrhythmias - initially atrial (associated with RA enlargement), then include ventricular
6. Therapy
   1. All patients should be followed at a referral (tertiary care) center
   2. Phlebotomy for hyperviscosity syndrome
   3. Endocarditis Prophylaxis
   4. Oxygen therapy as needed for patients with hypoxemia
   5. Avoid calcium blockers, antiplatelet agents, and anticoagulants
   6. Avoid volume depletion - iatrogenic and otherwise
   7. Heart-Lung Transplantation
   8. Surgery and pregnancy are very high risk in these patients
7. Survival 20-30 years without treatment

K. Ebstein's Anomaly [10]

1. Abnormal Tricuspid Valve
   1. Septal and often posterior leaflets diplaced into the RV
   2. Anterior leaflet usually malformed: excessively large, abnormally attached to RV
   3. Thus, the atrium extends into the RV, and the functional RV is small
   4. Valve is usually regurgitant, but may be stenotic
2. 80% of patients have atrial communication: ASD or PFO
3. Severity of disease depends on degree of valvular displacement and dysfunction
   1. Severe disease usually discovered as heart failure in a neonate
   2. Mild disease may be discovered incidentally as an adult
   3. Some adults will present as supraventricular arrhythmias
4. Neonates with severe disease have murmer, cyanosis and severe heart failure early on
5. Diagnosis
   1. Physical examination most notable for cyanosis and widely split S1 and S2
   2. A third or fourth heart sound is often present
   3. Hepatomegaly and V waves may be present
   4. ECG shows broad P waves and RBBB
   5. First degree atrioventricular block is common
   6. 20% of cases have ventricular preexcitation via accessory track (WPW Syndrome)
   7. These WPW cases often have delta wave on ECG
   8. Echocardiography used to evaluate RA size and other cardiac anomalies
6. Treatment
   1. Prevent and treat complications
   2. Endocarditis prophylaxis recommended
   3. Heart failure treated as usual, but with attention to maintaining preload
   4. Radiocatheter ablation of accessory tract is recommended
   5. Arterial shunt from systemic to pulmonary circulation may be created to increase flow to the pulmonary vasculature
   6. Repair is preferred to replacement of tricuspid valve
   7. Bioprosthesis is preferred over a metal valve

L. Transposition of the Great Arteries [10]

1. Complete and incomplete transpositions have been described
   1. In complete form, aorta arises in anterior position from the RV
   2. In complete form, pulmonary artery arises from the left ventricle
   3. Leads to complete separation of pulmonary and systemic circulation
2. Communication between right and left circulation must occur for infant to survive
   1. In ~35% of infants, an ASD, VSD, or PDA is present
   2. In ~65% of infants, no other cardiac defects are found
   3. In these infants, PDA and patent foramen ovale allow communication of blood
3. Symptoms and Signs
   1. Cyanosis with tachypnea
   2. Heart failure
   3. Second heart sound is single and loud (aorta is anterior)
   4. Chest radiograph shows cardiomegaly and increased pulmonary vascularity
4. Immediate management involves creating and/or increasing intracardiac mixing
   1. Prostaglandin E infusion maintains patent ductus arteriosus
   2. An ASD can be created with balloon atrial septostomy
   3. Oxygen decreases pulmonary vascular resistance and increases pulmonary blood flow
   4. Congestive heart failure (CHF) is treated as usual
   5. Benefits of ACE inhibitors in patients with right ventricular dysfunction being evaluated
5. Surgical Correction [18]
   1. Arterial switch operation is now done
   2. Pulmonary artery and ascending aorta transected above semilunar valves and coronaries
   3. Aorta is switched to the neoaortic (formerly pulmonary) valve
   4. Pulmonary artery is connected to neopulmonic valve
   5. Coronary arteries are relocated to the neoarta
   6. Excellent long term outcome: 94% 10 year survival
   7. 22% reoperation at 10 years

M. Pediatric Cardiomyopathy [21,22]

1. Incidence is ~1.1 per 100,000 per year
2. Highest risk is in infants <1 year (8/100,000 versus 0.70/100,000 for 1-13 years)
3. Classification [22]
   1. Dilated type: 51%
   2. Hypertrophic: 42%
   3. Restrictive
4. Lymphocytic myocarditis may be more prevalent in Australia [21]

N. Genetic Arrhythmic Syndromes [19]

1. Brugada Syndrome
   1. Type 1: SCN5a mutations, decreased Na+ current
   2. Type 2: mapped to chromosome 3p22-25, unknown ion channel dysfunction
2. Long QT Syndromes 1-6
3. Conduction System (Lenegre's) Disease: SCN5a mutations
4. Familial Atrial Fibrillation: mapped to chrom 10q22-24
5. Arrhythmogenic Right Ventricular Dysplasia (ARVD) [26]
   1. Autosomal dominant in most cases, multiple loci on chrom 1, 2, 3, and 14
   2. Chromsome 17q21 (Naxos): plakoglobin dysfunction
   3. Mutations in desmoplakin gene also implicated
   4. Result is Impaired function of myocytes and myocyte cell death
   5. Leads to fatty infiltration of myocardium
   6. Sudden arrhythmic death, syncope, CHF may develop
   7. ß-adrenergic blockers are first line
   8. Amiodarone or sotalol are used in patients with ventricular arrhythmias on ß-blockers
   9. Standard treatment for CHF in patients with symptoms

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