Congenital Heart Disease

Chapter 18
Congenital Heart Disease


I. Atrial septal defect (ASD)

A. Embryology (see Figure 18.1)

The interatrial septum has two parts:

  • A lower part connected to the endocardial cushions at the valvular level and called septum primum. The septum primum is thin and membranous.
  • An upper part called septum secundum. The septum secundum is thick and muscular.

These two septa meet and overlap. The overlap area is called fossa ovalis.1,2

In the fetus, the overlap area is not sealed, leaving a tunnel that allows blood to flow from right to left. This tunnel is called foramen ovale. In the fetus, oxygenated blood flowing from the IVC is directed towards the left heart through the septum secundum and foramen ovale, and is ejected into the ascending aorta, the brain, and upper body. Deoxygenated blood flowing from the SVC continues into the RV and is ejected into the high-resistance pulmonary circulation, then the descending aorta through the ductus arteriosus. Overall, the RV provides ~55% of the systemic cardiac output (lower body), while the LV provides ~45% of the systemic output (upper body). The pulmonary vascular resistance is elevated in the fetus, as a reaction to the poorly oxygenated lung, and the pulmonary arterial pressure is higher than the systemic pressure; at birth, the pulmonary resistance and pressure dramatically drop.

Schematic illustration of interatrial septum.

Figure 18.1 Interatrial septum. Embryologically, blood coming from the IVC is directed into the LA by the right-sided, septum secundum flap. The septum primum acts like a one-way door that opens when the RA pressure rises, and closes when the LA pressure supersedes the RA pressure, closing the foramen ovale. The prominent, septum secundum boundary of the fossa ovalis is called limbus (on the side of the RA).

Embryologically, The septum primum was initially localized at the upper portion of the RA. It grew down and touched the endocardial cushions, then developed a defect in its middle and top portions (ostium secundum) to allow blood shunting. This defect got covered by a growing muscular septum secundum, which eventually met the septum primum.

Schematic illustration of bicaval TEE view showing a PFO between the septum primum (thin, at bottom) and the septum secundum (thick, on top).

Figure 18.2 Bicaval TEE view showing a PFO between the septum primum (thin, at bottom) and the septum secundum (thick, on top). EV, Eustachian valve.

B. Pathology (see Figures 18.2, 18.3, 18.4)

  1. At birth, the PA pressure significantly drops and the pulmonary arterial and venous flow significantly increase. As a result, the LA pressure rises and pushes the septum primum to seal the overlap area.1 If it does not seal, a patent foramen ovale (PFO) persists. PFO is a persistent tunnel or flap; this is different from the gap of an ASD.2
  2. If the two septa do not meet and overlap, a wide, open gap will exist between the two septa in the middle of the interatrial septum: this is called ostium secundum ASD (70% of ASDs).
  3. If the septum primum does not connect with the endocardial cushions, a gap will be present at the lower level of the interatrial septum: this is ostium primum ASD (15–20% of ASDs). No atrial septal tissue is seen above the base of the atrioventricular valves.

    Ostium primum ASD may be continuous with a defect of the membranous ventricular septum, in which case the defect is called complete atrioventricular (AV) canal defect, or endocardial cushion defect. The endocardial cushions are central embryonic structures that develop into the AV valves and the membranous ventricular septum. In complete AV canal defect, no tissue separates the AV valves; the AV valves are actually one valve at one horizontal plane, with an atrial and ventricular septal defect in the middle.

    An ostium primum ASD without VSD is called partial AV canal defect. In the partial AV defect, the ventricular septum is closed by the endocardial cushions or by the septal tricuspid leaflet early in life, so that only a primum ASD is present. In another form called transitional AV canal defect, most of the ventricular defect is closed by the septal leaflets of the AV valve, so that only a small residual inlet VSD is seen and two AV valves are present. Thirty-five percent of patients with AV canal defect have Down syndrome, especially those with complete AV canal defects.

    Whereas normally the tricuspid valve is a bit lower (more apical) than the mitral valve, the tricuspid and mitral valves are at the same level in AV canal defect, as the mitral valve plane is pulled down. The down-pulling of the mitral valve elongates the LVOT, creating a “goose neck” narrowing of the LVOT with potential LVOT obstruction (Figure 18.5). Mitral valve defects (cleft valve) are frequently seen and result in eccentric MR; tricuspid defects may also be seen.

  4. Sinus venosus defect is a gap at the upper posterior part of the septum at the SVC–RA connection. It is almost always associated with some degree of anomalous pulmonary venous return, in which the right upper pulmonary vein, and sometimes a right middle or inferior pulmonary vein, drain into the RA.
Schematic illustration of types of ASD.

Figure 18.3 Types of ASD. Secundum ASD results from excessive involution of the top portion of the septum primum (→ does not meet the septum secundum). Primum ASD results from failure of the septum primum to reach the endocardial cushions. Thus, beside primum ASD, secundum ASD is also a defect of the septum primum. Septum primum is the thinner septum, marked by 1; septum secundum is marked by 2.

Schematic illustration of en face view of the interatrial septum.

Figure 18.4 En face view of the interatrial septum. Occasionally, both a PFO and a small ASD may be present: ASD in one plane where the septum primum has excessively involuted, PFO in the other planes where the two septa continue to overlap. Alternatively, PFO may be present with multiple small ASD holes.

Schematic illustration of goose-neck deformity of the LVOT in primum ASD.

Figure 18.5 Goose-neck deformity of the LVOT in primum ASD.

Partial anomalous pulmonary venous return may also be seen with secundum ASD. A right upper pulmonary vein draining into the RA or SVC is the most common anomaly, accounting for >90% of the anomalous venous return; a left pulmonary vein draining into the innominate vein may also be seen. If only one pulmonary vein is involved, the amount of shunting induced by the anomalous vein is, per se, mild. However, in conjunction with an ASD, the anomalous vein may significantly add to the shunt burden.

C. Consequences

  1. A significant ASD is an ASD with a prominent left-to-right shunt leading to a pulmonary flow (Qp) 1.5 times larger than the systemic flow (Qs): Qp/Qs ≥1.5/1.0.

    A large ASD is characterized by a Qp/Qs ≥2.

  2. A significant ASD causes RA/RV volume overload, dilatation, and failure. This may, rarely, occur in childhood if the ASD is large. Most patients are minimally symptomatic in the first three decades; exercise intolerance and hemodynamic compromise occur later in adulthood (30s to 40s), and most patients are symptomatic by the age of 50. AF and right heart failure develop by the age of 40 in ~10% of patients, then become more prevalent with age. In fact, for the same ASD size, left-to-right shunting may become more severe with age, as LV diastolic dysfunction occurs and LA pressure rises. Also, LA enlargement that occurs with age stretches and widens the ASD. ASD does not, by itself, lead to LA enlargement unless AF occurs.

    A complete AV canal defect, on the other hand, leads to a severe shunt and Eisenmenger syndrome early in infancy if not corrected.

    Paradoxical embolism may be seen.

  3. Pulmonary hypertension (PH) may occur but is rarely severe, because the RV usually fails before severe PH develops. In a way, the failing RV constitutes a barrier that protects the pulmonary arteries from volume overload. If PH is severe and ASD is <2 cm, a second causative diagnosis should be considered. Under 10% of ASDs develop significant pulmonary vascular disease with PVR >5 Wood units.3,4 Cyanosis and reversal of the shunt to a right-to-left shunt often result from RV failure and the consequent rise of RA pressure, even without any PH.

D. Diagnosis

  1. Exam:

    • Fixed split S2
    • Scratchy systolic ejectional murmur at the pulmonic area (left upper sternal border) due to the increased right-sided flow. The murmur may mimic pulmonic stenosis. P2 allows the distinction: P2 is attenuated in PS but part of a loud split S2 in ASD. Systolic TR murmur may also be heard.
    • RV heave
    • Increased JVP with a large V wave indicative of RV failure ± TR

  2. ECG:

    • Ostium secundum ASD: RBBB (usually incomplete), right axis deviation, R-wave notching in the inferior leads (crochetage), right atrial enlargement
    • Ostium primum ASD: RBBB + left axis deviation ± prolonged PR interval (primum ASD damages the infra-Hisian conduction system)
    • Sinus venosus ASD: ectopic atrial rhythm (non-sinus P waves)
    • AF or atrial flutter may be present

  3. CXR features: enlarged RV, enlarged central PA knob, and pulmonary plethora from increased flow.
  4. Echo:

    • TTE often establishes the diagnosis by visualizing the defect and the Doppler flow across it. The defect is usually >8 mm, as smaller defects usually close spontaneously in infancy and do not usually cause hemodynamic compromise. TTE can calculate Qp/Qs ratio (pulmonary to systemic flow ratio), which is equal to:

      • (velocity [VTI] × diameter) at the RVOT, divided by (velocity [VTI] × diameter) at the LVOT

      TTE also shows RA and RV enlargement, consequences of any significant ASD.

    • The subcostal view is orthogonal to the interatrial septum and is the best diagnostic view for ASD. Over 90% of secundum ASDs are seen in this view, which is also the best view for the sinus venosus defect and for assessment of shunt direction by spectral Doppler. However, the sinus venosus defect, or, rarely, other defects, may be missed by TTE. SVC view (right parasternal view) or superior angulation in a subcostal view may allow the diagnosis of sinus venosus defect. TEE permits better visualization if the diagnosis is suspected but not clearly established in a patient with RA/RV enlargement. Also, intravenous bubble injection may suggest the diagnosis of ASD in these patients. In PFO or secundum ASD, the bubbles fill the RA then the LA; in sinus venosus ASD, the bubbles simultaneously fill both the RA and LA.

  5. Right heart catheterization: catheterization permits the hemodynamic diagnosis of ASD (O2 saturation step-up ≥8% between SVC and RA), and permits Qp/Qs quantification.

E. Treatment

  1. Up to 62% of secundum ASDs may spontaneously close in the first year of life, especially ASD < 3–8 mm.
  2. Closure of ASD is indicated when ASD is anatomically large >10 mm with one of the following hemodynamic features:

    • Qp/Qs ≥1.5 in patients older than 1 year, including asymptomatic patients, as soon as possible. In infants < 1 year old, wait to see if spontaneous closure occurs.
    • Right-sided enlargement or failure. The calculation of Qp/Qs is particularly needed when ASD seems anatomically small and needs to be confirmed as the cause of RV failure, or when the shunt is bidirectional.

    In case of pulmonary hypertension, ASD closure remains indicated if there is still a net left-to-right shunt (Qp/Qs ≥1.5) and PVR is <1/3 SVR and <5 Wood units.5 ACC gives closure a class IIb when PVR is 1/3-2/3 SVR, and contraindicates it when PVR>2/3 SVR. ESC contraindicates closure when PVR ≥5 Wood units. However, ESC allows a trial of PAH therapy followed by re-evaluation of PVR (goal <5) and Qp/Qs (goal>1.5)

    Schematic illustration of interatrial septum viewed from the side.

    Figure 18.6 Interatrial septum viewed from the side. Various rims are identified. The three best TEE views to visualize the interatrial septum are:

    • 0° four-chamber view with a clockwise torque to the right (mitral and posterior rims)
    • 30–50° aortic view with a clockwise torque to the right (aortic and posterior rims)
    • Bicaval 90° view: from the 0° view torqued towards the right-sided structures, a 90° rotation allows visualization of the SVC and IVC (bicaval view) (SVC and IVC rims).

    The mitral and IVC rims are septum primum, while the aortic and SVC rims are septum secundum; the two septa meet in the middle. An ostium primum ASD is characterized by an absent mitral rim, while a sinus venosus ASD is characterized by an absent SVC rim.

  3. Note that ASD <10 mm in a patient older than 50–60 is often innocuous and unlikely to explain right heart failure or dyspnea (ESC). To the contrary, this small ASD may relieve RV failure or primary pulmonary hypertension via a pop-off right-to-left shunt. It may also relieve LV diastolic dysfunction, allowing the LA to decompress into the RA and reduce pulmonary edema. In fact, creating an 8-mm interatrial communication has been investigated as a therapy for HFpEF and has not shown RV or PA harm (induces a Qp/Qs of 1.27 only, despite the high LA pressure).6
  4. Closure is performed percutaneously or surgically (direct surgical closure or patch closure). Percutaneous closure can be used for secundum ASD that is ≤ 38 mm in diameter with 5 mm rims and without severe TR or anomalous pulmonary venous return (Figure 18.6). TEE or CT/MRI assessment of the rims and of the pulmonary veins, especially the right upper pulmonary vein, is critical in determining if the patient qualifies for percutaneous closure.

    Primum ASD and sinus venosus ASD are only treated surgically, as the lack of rims prevents device apposition.

  5. ASD closure improves survival and functional status, especially when performed at an early age. Closure before the age of 25 establishes a normal longevity (Mayo registry).3 Closure after the age of 40 in patients with right heart failure or Qp/Qs >1.5 does not re-establish normal longevity but still reduces long-term mortality by 70% and improves functional status.4 The reduction of right heart volume starts early after closure, within 24 hours, and may continue for over a year. This reverse remodeling is more complete in younger patients.

    While improving survival and functional status, closure in patients >40 years of age does not prevent AF or stroke.

  6. Secundum ASD does not require endocarditis prophylaxis. After correction and in the absence of a residual shunt, patients require endocarditis prophylaxis for 6 months only (i.e., until the surgical site endothelializes). If a residual defect persists, endocarditis prophylaxis is indicated lifelong.

II. Patent foramen ovale (PFO)

A cryptogenic stroke is a stroke that is unexplained by carotid disease, cardiac disease such as AF or LV thrombus, or prothrombotic coagulopathies (mainly antiphospholipid syndrome). Moreover, to make the diagnosis of a cryptogenic stroke, a lacunar stroke must be excluded (lacunar stroke being a small, deep white-matter stroke < 15 mm in a patient with HTN, diabetes, or age >50). There is an association between PFO and cryptogenic stroke, patients with cryptogenic stroke having a higher prevalence of PFO than the normal population (~40–50% prevalence). This association is particularly established in patients < 55 years old and is uncertain in older patients.7,8 PFO patients may have paradoxical embolization of a DVT or an in situ thrombosis formed at the PFO level, especially if the interatrial septum is hypermobile and ejects it.

PFO is common in the normal population (prevalence ~25%), and thus a causal relationship with a stroke is, at best, a diagnosis of exclusion. In some, but not all studies, a large shunt or the coexistence of an atrial septal aneurysm had a clearer association with stroke.7,8 A large shunt is defined as >10–30 microbubbles or PFO tunnel width ≥2–4 mm, meaning that the separation between secundum septum and primum septum is ≥2–4 mm. An atrial septal aneurysm, defined as hypermobility of the thin septum primum >1 cm from midline, is less clearly associated with an increased stroke risk when isolated.8 The combination of the following three patient characteristics increases the probability that the stroke is PFO-related: age < 55, cortical location of the stroke (as opposed to deep white matter or periventricular), and the lack of uncontrolled HTN, uncontrolled diabetes, and smoking.

PFO is diagnosed by TTE or TEE performed with microbubbles/agitated saline injected during Valsalva (bubble study). In case of PFO, these bubbles will go from the RA to the LA within 3–5 cardiac cycles during the Valsalva release phase. Even the shunting of one bubble to the LA indicates the presence of a right-to-left shunt. If it takes >3–5 cycles for the bubbles to appear on the left side, the shunt is at the pulmonary level (e.g., AV malformation). Normally, during quiet breathing, the LA pressure is larger than the RA pressure, thereby closing the septum primum towards the septum secundum and preventing any significant shunting, except very briefly. A physiologic right-to-left shunt occurs when the RA volume suddenly and largely increases at a time when the LA volume does not, which reverses the LA–RA pressure differential; this is seen during deep inspiration or during the release phase of the Valsalva maneuver. Conversely, the strain phase of Valsalva may reduce right venous return and right-to-left shunting. Of note, bubble injection via a lower extremity vein (into the IVC) is more likely to be shunted through the PFO.

Treatment of a cryptogenic stroke presumably due to PFO

  • Aspirin or warfarin. The PICSS trial, a large trial that compared aspirin to warfarin in patients with cryptogenic stroke, did not find any difference in stroke recurrence between the two therapies in patients with PFO.7
  • In patients who had one or more cryptogenic strokes/TIAs, PFO closure is superior to medical therapy in reducing stroke recurrence, according to three randomized trials.9–11 The risk of stroke recurrence after a cryptogenic stroke is relatively low, 5–6% at 5 years under antiplatelet therapy (as seen in all three PFO trials).811 While low, this risk is cumulative over time and is particularly consequential in young patients over the long term. PFO closure reduces stroke risk by ~0.5% per year, which becomes significant upon long-term follow-up. PFO closure is indicated in young patients <55 years with cortical stroke and no smoking, diabetes, or HTN, and no AF on rhythm monitoring. In 2 of the 3 major trials and in a meta-analysis, the benefit appeared limited to patients with either a large PFO or an associated atrial septal aneurysm.9,10

III. Ventricular septal defect (VSD)

A. Types (see Figure 18.7)

The interventricular septum has a small membranous portion and a large muscular portion. The muscular portion is divided into three zones (inlet between the atrioventricular valves, outlet beneath the great arteries, and trabecular). A VSD is either perimembranous or muscular:13

  1. Perimembranous VSD is the most common VSD (70–80% of VSDs). It involves the membranous septum and extends a bit into one of the three muscular regions (inlet, trabecular, or outlet). An entirely membranous VSD is rare, as the membranous septum is a small fibrous center.
  2. Muscular trabecular VSD is the next most common VSD.
  3. Inlet VSD. The inlet septum separates the septal cusps of the mitral and tricuspid valves. Inlet VSD is mainly a defect of the muscular inlet septum, but the membranous septum is frequently involved. A gross deficiency of the inlet septum is associated with AV canal defect. Conversely, a small inlet VSD is not usually associated with AV canal defect.13
  4. Outlet VSD (subarterial or infundibular VSD). Outlet VSD is mainly a defect of the muscular outlet septum, but the membranous septum is frequently involved. When outlet VSD is very high and abuts both arterial valves, it is called supracristal VSD or doubly committed VSD (the crista supraventricularis being a muscular ridge in the RV outflow).

B. Consequences and associations

  • A large VSD leads to a left-to-right shunt, with progressive pulmonary hypertension and progressively large volume circulating back to the LV and leading to LV failure from volume overload. As pulmonary hypertension becomes more severe, Eisenmenger syndrome and cyanosis occur.
  • A VSD, especially an outlet VSD, may be associated with aortic insufficiency. This results from high-velocity jet lesions, similarly to what occurs with subaortic membranous stenosis; also, the outlet defect diminishes the cuspal support and may lead to aortic cusp(s) prolapse. Outlet VSD may be associated with subpulmonic or subaortic stenosis; the subpulmonic stenosis may lead to a right-to-left shunt but protects from Eisenmenger syndrome.

    Any VSD may also be associated with a bicuspid aortic valve and coarctation of the aorta.

  • The membranous septum has an interventricular portion but also a more proximal (posterior) portion that separates the LV from the RA. A Gerbode defect is a perimembranous VSD extending more proximal to the tricuspid insertion, leading to a high-velocity LV-to-RA shunt and RV failure, in addition to the LV-to-RV shunt (Figure 18.8).

C. Exam and natural history

With the exception of bicuspid aortic valve, VSD is the most common congenital defect in children. A small VSD leads to a loud, harsh pansystolic murmur at the left lower sternal border, sometimes with a thrill, whereas a large VSD has a softer murmur. Thus, a loud murmur implies a more benign VSD than a soft murmur. Small VSDs are called restrictive because they allow only limited shunting.

Schematic illustration of anatomic and echocardiographic localization of VSD.

Figure 18.7 Anatomic and echocardiographic localization of VSD. The membranous septum is bordered by the septal tricuspid leaflet on the right and the subaortic area on the left; it is superior to the mitral valve. Perimembranous VSD is actually a superior/anterior form of VSD, and therefore it is seen on the long-axis echo view. Inlet VSD is bordered by the tricuspid valve on the right and the mitral valve on the left and is the one that continues with an atrial septal defect to form the AV canal defect.

Note that the pulmonic valve (PV) is higher and more anterior than the aortic valve (AoV), and the outlet septum is larger on the right than the left side. An outlet VSD that extends all the way to the PV is called supracristal VSD.

Schematic illustration of gerbode defect on an apical five-chamber view.

Figure 18.8 Gerbode defect on an apical five-chamber view. Perimembranous VSD extends more proximal to the tricuspid valve and leads to LV–RA shunt, in addition to the LV–RV shunt. Being a perimembranous defect, it may not be seen on the four-chamber view. The defect may have an inlet extension.

Small perimembranous or trabecular VSDs have a high closure rate (50–80%) by 2–10 years of age. A perimembranous VSD may close by the apposition of the septal tricuspid leaflet, which sometimes forms a pouch at the level of the sealed defect.15 A small VSD is hemodynamically insignificant, and remains so as the patient ages, but is associated with a risk of endocarditis.

Large VSDs (non-restrictive, Qp/Qs >2) have a low spontaneous closure rate and lead to left HF, then Eisenmenger syndrome in infancy or childhood. They are typically corrected early on, before 1 year of age. Moderately large VSDs (Qp/Qs 1.4–2) may be tolerated for years before leading to hemodynamic compromise later on, in adulthood, as LV systolic and diastolic pressures rise and increase L-R shunting.

Adults presenting with VSD usually have a small VSD that did not close spontaneously and is not leading to any hemodynamic compromise. Other possibilities are: patch leak of a surgically repaired VSD; moderate VSD that is leading to hemodynamic compromise in adulthood (unusual); or large, non-corrected VSD that led to Eisenmenger syndrome long before adulthood. Also, infective endocarditis and AI may be seen later in life with a small, seemingly insignificant adult VSD.

D. Diagnosis, location, and shunt fraction Qp/Qs are established by TTE

TTE allows estimation of the VSD size: a small VSD has a diameter smaller than 1/3 of the aortic root diameter, a large VSD is a VSD larger than the aortic root. A large VSD typically has a large Qp/Qs ratio (>2), a small velocity, and a small pressure gradient across it because of the high RV systolic pressure (non-restrictive VSD).

TTE may miss a small trabecular VSD but very rarely misses other types of VSD.

E. Treatment

Surgical closure (direct closure or patch closure) is indicated as soon as possible for:

  • Significant VSD (moderately restrictive or large non-restrictive) with a Qp/Qs ≥1.5 and without severe pulmonary vascular disease (as under ASD treatment).
  • Large VSD with LV or LA dilatation or LV dysfunction.
  • Outlet VSD with progressive AI, regardless of its size.

Perform the surgery soon in infancy if needed (at the age of 3–6 months). Postoperative patch leaks may be seen but rarely require reoperation. Occasionally, if VSD closure cannot be immediately performed, PA banding is performed to reduce the pulmonary flow and the risk of Eisenmenger syndrome before definitive surgery.

IV. Patent ductus arteriosus (PDA)

A. Definition and consequences

PDA is a persistent communication between the left pulmonary artery and the descending aorta just distal (~1 cm) to the left subclavian artery. It leads to left-to-right shunt and massive LV volume overload from the shunt volume that circulates back to the LV. LV failure, which is initially a high-output failure, subsequently ensues (left HF being the most common complication).

It can also lead to progressive pulmonary hypertension and Eisenmenger syndrome with shunt reversal to a right-to-left shunt. In this case, a differential rather than a generalized cyanosis is seen (cyanosis of the feet only). The right-to-left shunt occurs distal to the innominate artery, so that the O2 saturation in the upper extremities is preserved whereas the O2 saturation in the lower extremities is low, explaining the differential cyanosis and clubbing, i.e., cyanosis that is much more prominent in the lower extremities. The origin of the left subclavian artery may be close enough to the ductus to receive unoxygenated blood, and therefore cyanosis and clubbing of the left hand may be seen. The right hand remains normal until a severely reduced cardiac output leads to generalized cyanosis.

Infectious endarteritis at the shunt level may also be seen.

B. Severity and presentation

Spontaneous closure of a PDA is unlikely in term infants older than 3 months or pre-term infants older than 12 months. A large shunt (Qp/Qs >2) is symptomatic in infancy and leads to Eisenmenger syndrome early on, as early as 8 months, if untreated.

A moderate shunt (Qp/Qs 1.5–2) may lead to hemodynamic compromise at a later age (childhood or adulthood, up to the third decade). A small shunt (Qp/Qs <1.5) presents as an isolated murmur.

A loud, continuous “machinery” murmur is heard at the first or second left intercostal space. As a result of the large stroke volume, the pulse pressure is wide with bounding pulses.

Nov 27, 2022 | Posted by in CARDIOLOGY | Comments Off on Congenital Heart Disease

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