Common congenital cardiac anomalies with a L-R shunt Atrial septal defects (ASDs),Partial anomalous pulmonary venous return, Ventricular septal defects (VSDs), and Patent ductus arteriosus (PDA)

Common congenital anomalies with a left to right shunt: Atrial septal defects (ASDs),  Partial anomalous pulmonary venous return, Ventricular septal defects (VSDs), and Patent ductus arteriosus (PDA)

Atrial septum defect (ASD)

An atrial septal defect (ASD) is a congenital defect in the interatrial septum allowing a direct communication between the atria. It is common, about 10% of all congenital heart disease cases, more common in females. (male to female ratio of 1:2).
There are three main types of ASDs:
Secundum ASD, the most common type (70-75% of ASDs) is located in the central portion of the interatrial septum.
Primum ASD, about 20% of all ASDs, (or partial endocardial cushion defect ) is in the lower part of the septum, near the atrioventricular valves. This is the second most common type. 

Primum ASDs are a part of the spectrum of endocardial cushion defects. They are often accompanied by a cleft in the anterior leaflet of the mitral valve, causing mitral regurgitation. A complete endocardial cushion defect (complete atrioventricular canal defect) is a more complex congenital anomaly consisting of a primum ASD, a ventricular septal defect of the inlet type, and anomalies of the atrioventricular valves (a common atrioventricular valve). Endocardial cushion defects are commonly seen in patients with trisomy 21 (Down syndrome).
Sinus venosus defect is located near the entrance of the superior vena cava (SVC) or the inferior vena cava IVC to the right atrium and is a less common type (about 5-10% of all ASDs), commonly associated with a partial anomalous pulmonary venous return.

Pathophysiology of atrial septal defects ( ASDs)

An ASD causes an abnormal flow between the atria, called a left to right (L-R) shunt, i.e. flow of blood through the defect with a direction towards the right heart chambers. This results in a volume overload to the right atrium and right ventricle and an increase in blood flow through the pulmonary arterial circulation. The magnitude of the L-R shunt depends upon the size of the defect and also the relative pressures on the left and right sides of the heart.

Clinical, electrocardiographic and echocardiographic findings in atrial septal defects 

The patients are asymptomatic in the majority of cases but large defects can be associated with recurrent respiratory infections, shortness of breath on exertion (dyspnea), easy fatiguability, or atrial arrhythmias (palpitations). Patients with large defects, late in the course can develop complications, such as right heart failure, or pulmonary arterial hypertension PAH (see also chapter Pulmonary Hypertension). Another rare complication of an ASD is a stroke due to paradoxical embolism (caused by a thrombus reaching the right atrium from the venous circulation and then crossing the ASD and entering the left cardiac chambers and the arterial circulation).
In a moderate or large ASD, physical examination findings usually include a widely split and fixed second heart sound (S2) and a systolic ejection murmur of low intensity, (grade 2 to 3/6) at the upper left sternal border (at the area of the pulmonary artery due to the increased blood flow through the right heart and the pulmonary artery).
In case of a large ASD with a large L-R shunt, a mid-diastolic rumble may be audible at the left lower sternal border, i.e. at the tricuspid area due to the increased flow through the valve.
The typical auscultatory findings often are not present in infants and toddlers, even with a large defect, because at this age the right ventricle often is not compliant enough to allow a large L-R shunt.
The ECG usually shows a RBBB, or an incomplete RBBB with an rsR′ pattern in V1 (also see chapter The Electrocardiogram -ECG . In case of a moderate to large ASD, right QRS axis deviation (frontal axis between +90 to +180°) and/or other indications of right ventricular hypertrophy may be present, but in the case of an ostium primum defect, there is an RBBB pattern with a left QRS axis.
Chest radiographs if the shunt is moderate or large, show cardiomegaly (with right atrial and right ventricular enlargement), increased vascular markings in the lungs and a prominent main pulmonary artery (at the mid-left heart border).
Echocardiography in a patient with an atrial septal defect (ASD) shows the position and the size of the defect and the abnormal flow (shunt) through the interatrial septum. If the defect is moderate to large, echocardiography also shows a dilated right atrium, right ventricle, and pulmonary artery. The finding of dilated right heart chambers proves that the ASD is hemodynamically significant and is in favor of ASD closure.
Cardiac catheterization is not necessary for the diagnosis of an ASD, but it can be necessary in the case of significant pulmonary hypertension to decide if the defect should be closed.

An asymptomatic female 14 years old with a low -intensity systolic ejection murmur at the upper left sternal border This is a modified apical 4 chamber view. Are there any abnormalities? What do the numbers 1-5 show? What treatment do you propose? (ALSO SEE THE VIDEO (two paragraphs below).

1. Right atrium (enlarged -compare with the left one)
2. Right ventricle (enlarged-compare with the left one)
3.Left atrium
4.Left ventricle
5. A color jet passing through the midportion of the atrial septum with a direction from left to right. It is a left to right shunt of blood at the midportion of the atrial septum due to a secundum ASD. Closure of the defect is indicated because the L-R shunt is significant enough to result in right heart chamber enlargement. In this case, transcatheter device closure was successfully performed.

Natural history of atrial septal defects (ASDs)

Spontaneous closure of an ASD often occurs in patients with secundum ASDs with a diameter < 8mm before the age of 1.5 years, but an ASD >8 mm rarely closes spontaneously.
After the age of 4 years, spontaneous closure is not likely to occur.
Spontaneous closure may occur only in secundum defects. It does not occur in primum or sinus venosus ASDs. If a large ASD is left without closure, pulmonary hypertension and signs of right heart failure can develop in the third or fourth decade of life.

Management of atrial septal defects

 In a patient with an ASD exercise restriction is not required unless the patient has symptoms.
Children with a secundum atrial septal defect are usually observed without intervention for at least the first 3 years of life, due to the possibility of spontaneous closure.
Closure of an ASD in children or adults, is indicated when there is evidence of right ventricular volume overload (a dilated right ventricle) in the presence of an atrial septal defect with size > 5 mm and in the absence of irreversible pulmonary arterial hypertension. In this case measurement of the ratio of pulmonary to systemic flow (Qp/Qs) is not necessary to confirm that the ASD is hemodynamically significant. If the ratio Qp/Qs is used, then the defect is considered hemodynamically significant and closure is decided if Qp/Qs ≥ 1.5:1, in the absence of irreversible pulmonary arterial hypertension. Closure of an ASD can be surgical or with a catheter device. Device closure is the preferred method when feasible, but it is only feasible in patients with a secundun ASD with a diameter ≥5 mm but < 32 mm for Amplatzer device and <18 mm for Helex device, provided there is enough rim ( at least 4 mm) of septal tissue around the defect ( for the appropriate placement of the device). The rim around the ASD is measured with 2-D echocardiography in 4 directions. After device closure of an ASD antiplatelet treatment is given, with aspirin 80-100 mg per day for 6 months. In children, device closure can be performed preferably if they weigh >15 kg.In the rare case of an ASD with pulmonary hypertension, closure of the ASD is indicated if systolic pulmonary arterial pressure is <2/3 of systemic systolic blood pressure and pulmonary vascular resistance <2/3 of systemic vascular resistance. If systolic pulmonary artery pressure and pulmonary vascular resistance exceed the above limits, ASD closure can be decided only when there is a L-R shunt with a ratio of pulmonary to systemic flow Qp / Qs of at least 1.5: 1,  provided that pulmonary hypertension is reversible.

A case (Video) showing the ECG and echocardiographic features of this condition

Partial anomalous pulmonary venous return 

This is a congenital anomaly, causing a L-R shunt. One or more (but not all) pulmonary veins drain into the right atrium directly or indirectly by draining into a systemic vein (e.g. into the superior vena cava , inferior vena cava, left innominate vein). The right pulmonary veins are more often involved. They may drain into the right atrium, or into the superior vena cava (in this case, often there is also an associated ASD of the sinus venosus type), or into the inferior vena cava in association with an intact atrial septum.
When the left pulmonary veins are involved, they drain into the left innominate vein or into the coronary sinus. Partial anomalous pulmonary venous return has many of the physiologic characteristics of an atrial defect (ASD) and it is also often associated with an ASD. Therefore, this condition is usually discussed in the same chapter with the ASD. Most often, there is an associated ASD, but in some cases, partial anomalous pulmonary venous return is present without an ASD.
The hemodynamics are those of an atrial defect, i.e. this condition also causes volume overload of the right atrium and the right ventricle and increases flow through the pulmonary circulation.
On clinical examination, a difference of an isolated partial anomalous pulmonary venous return from an ASD is the following: In the absence of a concomitant ASD, although the second heart sound (S2) can be widely split, this wide split of S2 is not fixed relative to respiration.
Similar to an ASD, often a midsystolic murmur (grade 2/6-3/6) is heard at the upper left sternal border, due to the increased flow through the pulmonary artery. Occasionally, a mid-diastolic rumble may also be present, resulting from increased flow through the tricuspid valve.
When there is an isolated partial anomalous pulmonary venous return without an ASD, this condition only rarely causes symptoms and the development of pulmonary hypertension is extremely rare.
ECG and radiographic findings are similar to those of an ASD: The ECG is normal or with RBBB or indications of right ventricular hypertrophy. The chest X-ray may demonstrate mild to moderate cardiomegaly due to the enlargement of the right heart chambers, prominence of the main pulmonary artery and increased vascular markings in the lungs.
Echocardiography should lead to the suspicion of partial anomalous pulmonary venous return when there is an enlargement of the right ventricle and atrium, without any other obvious cause and inability to visualize all four pulmonary veins. In normal infants and children, the suprasternal coronal "crab" view typically demonstrates the connection of the four pulmonary veins to the left atrium. The absence of any normal pulmonary venous connection to the left atrium should raise a suspicion of an anomalous pulmonary venous return. Transthoracic echocardiography (TTE) can demonstrate the dilated right ventricle and right atrium and it can often also demonstrate anomalous cardiac connections, but extracardiac connections may be difficult to identify on TTE. The demonstration of anomalous pulmonary venous return with extracardiac connections typically requires magnetic resonance imaging (MRI) or computed tomography (CT).
Partial anomalous pulmonary venous return is often found in patients with an ASD. The ASD can be of any type, although a sinus venosus ASD is most commonly associated with anomalous pulmonary venous return. A sinus venosus ASD often is associated with abnormal drainage of the right upper pulmonary vein. In the presence of diagnostic difficulties, cardiac MRI can establish the diagnosis of partial anomalous pulmonary venous return.

Treatment of partial anomalous pulmonary venous return.

Surgery is indicated if there is a significant left-to-right shunt with a Qp/Qs ratio > 2:1. Surgery is also indicated if patients demonstrate evidence of right heart volume overload (dilated right heart chambers on echocardiography) or symptoms.  Surgery, when needed, is performed at an age of 2 -5 years. When there is only an anomaly of one pulmonary vein, without an ASD, surgery is not undertaken.

Ventricular septal defects (VSDs)

There are four anatomic types depending on the location of the defect.
Perimembranous or membranous VSD is the most common type (70%) and it involves the membranous septum, a small part of the septum immediately beneath the aortic valve. These defects usually also have an accompanying defect of the adjacent muscular septum and depending on the location of this defect they are further classified as perimembranous trabecular, perimembranous inlet or perimembranous outlet.
Another type of VSDs are inlet defects, which are located beneath the septal leaflet of the tricuspid valve.
Outlet VSDs, also called conal or supracristal, are located in close proximity to the annulus of the aortic valve and of the pulmonary valve. These two valve annuli form part of the defect's rim. A common complication of this defect involves herniation of the right coronary cusp of the aortic valve through the defect. This can cause a reduction of the shunt, but also it often causes progressive aortic regurgitation. It may also result in a degree of obstruction of the right ventricular outflow tract.
Trabecular (muscular) VSDs may be central or apical, depending on their location in the muscular interventricular septum.

Pathophysiology of ventricular septal defects (VSDs)

The main pathophysiologic feature of a VSD is a left to right (L-R) shunt. The magnitude of the shunt depends on the size of the defect and the pressure difference between the two ventricles, which in turn depends on the pulmonary arterial pressure and thus, on the level of the pulmonary arterial resistance. The larger the size of the defect and the lower the pulmonary vascular resistance, the larger the L-R shunt. 
A small defect does not cause any ventricular dilation or hypertrophy, a moderate-sized defect usually can cause left ventricular hypertrophy or dilation and a large defect can cause hypertrophy or dilation of both ventricles. Moreover, a small VSD, also called a restrictive VSD, has a large resistance and results in a significant pressure gradient between the two ventricles and a small shunt with Qp/Qs<1.5 :1 and pulmonary systolic pressure/systemic systolic pressure<0.3. 
On the contrary, a large nonrestrictive defect will cause a large shunt with Qp/Qs >2.2 and a small pressure gradient between the two ventricles. Pulmonary arterial systolic pressure/systemic systolic arterial pressure will be > 0.6. With a VSD of a moderate size these values will be intermediate, with a Qp/Qs between 1.5 and 2.2.
A large VSD if left untreated will cause over the years a progressive rise of the pulmonary vascular resistance, due to progressive obstructive changes of the pulmonary arterioles. This leads to an elevated pulmonary arterial and right ventricular systolic pressure resulting in a reduction in the magnitude of the L-R shunt. This condition has also effects on the ventricles with the left ventricle decreasing in dimensions, whereas the size of the right ventricle increases. When the obstructive changes in the pulmonary vasculature become serious and irreversible, bidirectional shunt develops across the VSD (or even net right to left R-L shunt) and this leads to the development of cyanosis because unoxygenated venous blood from the right ventricle enters the left ventricle and the systemic circulation.

Symptoms and signs of a VSD

In infants and children, a small restrictive defect does not cause any symptoms and is diagnosed because of the auscultation of a murmur. A large non-restrictive VSD can cause dyspnea, failure to thrive and signs of congestive heart failure early, even at the age of 2-3 months, or later. In adults a small restrictive defect will be asymptomatic (and the only sign will be the murmur), a defect of a moderate size may cause dyspnea on exertion and palpitations due to the development of atrial fibrillation, whereas a large non-restrictive VSD can cause symptoms and signs of right heart failure and central cyanosis (Eisenmenger syndrome). Apart from cyanosis patients with Eisenmenger syndrome often have edema (due to the right-sided heart failure) and clubbing.
The murmur of a VSD is pansystolic (holosystolic, i.e. it is present during the whole duration of systole), grade 2/6-5/6, best heard at the lower left sternal border. The murmur can be accompanied by a palpable systolic thrill (also at the lower sternal border). The murmur occasionally can be early systolic in patients with small muscular VSDs.
Murmurs of increased flow may be audible if the shunt is moderate to large, such as a systolic murmur due to increased flow through the pulmonary valve, or an apical diastolic rumble due to increased flow through the mitral valve (The L-R shunt causes not only increased flow through the pulmonary valve and the pulmonary circulation, but also an increased flow through the mitral valve which also leads to volume overload of the left ventricle. This happens because as a result of the increased flow through the pulmonary circulation, there is also an increased pulmonary venous return of blood to the left atrium).
If pulmonary hypertension develops, the pulmonic component (P2) of the second heart sound becomes loud (generally a loud P2 is a sign indicative of pulmonary hypertension, regardless of the etiology). With the development of pulmonary hypertension the systolic murmur of a VSD becomes less prominent and if severe pulmonary hypertension develops the murmur usually disappears. This happens because in the presence of pulmonary hypertension there is a smaller pressure difference between the left and right ventricle resulting in a reduction in the flow of blood through the defect from the left into the right ventricle.

The ECG and the chest X-ray in patients with a VSD

In patients with a small restrictive VSD both the ECG and the chest X-ray are usually normal. In patients with a defect of moderate size the ECG will usually show features of left ventricular and left atrial hypertrophy and enlargement respectively and in a large non-restrictive defect left atrial enlargement with combined ECG features of left and right ventricular hypertrophy. In the case of pulmonary vascular obstructive disease with pulmonary hypertension the ECG usually shows features of isolated right ventricular hypertrophy.
The chest X-ray in the case of a VSD with a moderate or large shunt will show enlargement of the cardiac silhouette (due to dilation of the left atrium and ventricle and occasionally also the right ventricle). A moderate to large shunt will also result in increased pulmonary vascular markings (to a degree that is in direct proportion to the magnitude of the L-R shunt). If pulmonary vascular obstructive disease with significant pulmonary arterial hypertension has developed, the main pulmonary artery and its main branches at the hila of the lungs are dilated, while there are markedly reduced pulmonary vascular markings at the lung fields (this is a typical chest X-ray pattern of pulmonary arterial hypertension of any cause).

Echocardiography in a patient with a ventricular septal defect

Transthoracic echocardiography can identify the presence of a VSD, from the turbulent jet of flow across the interventricular septum, and it can also demonstrate the location and size of the defect and it can provide information about its hemodynamic significance. An increased left ventricular and left atrial size (and also a Qp/Qs>1.5) indicates the presence of a significant (moderate or large) L-R shunt.
 With the exception of the trabecular VSDs, a useful marker for the identification of the type of the VSD is its location relative to the valves. A membranous defect is near the aortic valve, an infudibular defect near both the pulmonic and the aortic valve and an inlet defect near the tricuspid valve.

From the peak gradient across a VSD measured with continuous wave Doppler, by subtracting this gradient from the systolic arterial pressure, the right ventricular systolic pressure (RVSP) can be calculated. RVSP is equal to PASP (pulmonary artery systolic pressure) if there is no coexisting stenosis of the right ventricular outflow tract or the pulmonary valve.

A young woman with a harsh holosystolic murmur best heard at the mid-to lower left sternal border. Echocardiogram left parasternal long axis view. What is the cause of the patient's cardiac murmur ?

The cause of the murmur is a small perimebranous VSD.
1. The jet of turbulent high velocity flow originating from the left ventricle just proximal to the aortic valve and entering the right ventricle is shown (with color flow Doppler)  2. left ventricle, 3. aorta, 4. left atrium.

Cardiac catheterization

Cardiac catheterization is not needed for the diagnosis of a VSD, but only if there is pulmonary hypertension to calculate the pulmonary vascular resistance and in some cases where echocardiography does not fully clarify the anatomic diagnosis, or if there is a significant possibility of coronary artery disease. In a VSD with a L-R shunt cardiac catheterization will reveal an elevated oxygen saturation in the pulmonary artery, and this is also an indication that there is no severe pulmonary hypertension. In case that severe pulmonary hypertension has developed this will result in a significant reduction in the L-R shunt and so, much less oxygenated blood from the left ventricle will enter the right ventricle and the pulmonary artery. Therefore, in this case, the oxygen saturation in the pulmonary arterial blood will be low. In these cases, simultaneous comparison of the pulmonary arterial and systemic blood pressures is mandatory, as well as calculation of the pulmonary vascular resistance and assessment of its response to vasodilators. This assessment is necessary to demonstrate if pulmonary arterial hypertension is reversible or irreversible.

The natural history of ventricular septal defects (VSDs)

Membranous and muscular VSDs can decrease in size with time, or close spontaneously. Until the age of 6 months spontaneous closure occurs in about 30-40% of these defects. On the contrary, inlet or infudibular defects do not decrease in size and thus they also do not demonstrate spontaneous closure.
In infants with large VSDs congestive heart failure can occur but usually after the first 6-8 weeks of life, because at that time the pulmonary vascular resistance has fallen enough to allow a large L-R shunt which can cause severe volume overload of the left heart chambers due to the increased pulmonary venous return.
Large VSDs can cause a slowly progressive elevation of the pulmonary arterial pressure. This is the result of progressive obstructive changes in the pulmonary arterioles as a reaction of the pulmonary arterial circulation to the chronically increased blood flow. Although pulmonary vascular changes may begin early, even at an age of 6-12 months, severe pulmonary arterial hypertension leading to a R-L shunt and the appearance of cyanosis usually does not occur before the second decade of life.
Another complication that can develop in some infants with a large VSD is infudibular stenosis, i.e. stenosis of the right ventricular outflow tract just below the pulmonary valve. This reduces the L-R shunt and in some cases it may even cause the development of a R-L shunt with cyanosis, a condition similar to the tetralogy of Fallot.

Treatment of the patient with a VSD

In infants with large defects usually medical treatment is given initially (furosemide, ACE inhibitor) to control heart failure, while waiting for the gradual spontaneous decrease in the size of the defect, but if this does not happen or if there is inadequate control of the manifestations of congestive heart failure then closure of the defect is decided.
In children and adults indications for VSD closure are the following: A VSD of a hemodynamically significant size, i.e a defect causing symptoms or dilation of the left ventricle, or a gradual worsening in left ventricular function, or Qp/Qs> 1.5:1 or an elevation in pulmonary arterial pressure > 50 mmHg but in the last case with a pulmonary vascular resistance <7 Wood Units. If the pulmonary vascular resistance > 7 Woods then the defect is closed if there is a shunt with a Qp/Qs> 1.5 : 1 or reactivity of the pulmonary circulation to vasodilators has been demonstrated (a fall in pulmonary vascular resistance and pulmonary arterial pressure with vasodilators). If there is irreversible pulmonary arterial hypertension and Eisenmenger syndrome then closure of any pathologic communication between the left and right circulation (such as a VSD or an ASD) is contraindicated.
Another indication for the closure of a VSD is related to the development of aortic regurgitation as a complication of an outlet VSD, which can be progressive. There is an indication for closure if such a VSD causes more than mild AR.

A video. Echocardiogram of a woman (age 22) with a small perimebranous ventricular septal defect. From the you tube channel 
Julián Vega Adauy  LINK to the Video: perimembranous ventricular septal defect-echocardiogram

Patent ductus arteriosus (PDA)

The ductus arteriosus is a vessel of the fetal circulation which forms a communication between the proximal descending aorta, just distal to the origin of the left subclavian artery and the bifurcation of the pulmonary artery. This vessel is open in the fetus, but it normally closes immediately after birth. The closed ductus after birth will normally form the ligamentum arteriosum.
A patent ductus arteriosus (PDA) is a congenital anomaly occurring when the ductus fails to close after birth, occurring in 1:2000 live births. It is more common in females. Factors increasing the risk for a PDA are premature birth, maternal rubella, birth at a high altitude and genetic factors.
A PDA causes a left to right ( L-R) shunt with a direction from the aorta to the pulmonary artery, because the pressure in the aorta is higher than that of the pulmonary artery.  
A PDA (patent ductus arteriosus) is classified based on its size and the magnitude of the L-R shunt. A measure of the magnitude of the shunt is Qp/Qs (the ratio of pulmonary to systemic flow).
• A silent PDA: very small duct, no murmur on clinical examination, usually detected only on echocardiography
• A small PDA : A continuous murmur is present. Qp/Qs <1.5
• A moderate PDA: A continuous murmur is present. Qp/Qs between 1.5 and 2.2
• A large PDA: A continuous murmur is present. Qp/Qs > 2.2
• PDA with Eisenmenger syndrome: Significant pulmonary hypertension with reversal of the shunt direction (R-L, i.e., from the pulmonary artery to the aorta). This causes differential cyanosis (cyanosis in toes and not fingers). In this case, the murmur is only systolic or inaudible (not heard).

Pathophysiology of patent ductus arteriosus

A patent ductus arteriosus (PDA), when it is of a moderate or large size, pathophysiologically causes:
1) Increased flow in the pulmonary circulation. This happens because, in addition to the normal flow of blood from the right ventricle through the pulmonary artery to the lungs to get oxygenated, an additional amount of blood enters the pulmonary circulation through the ductus.

2) Left ventricular volume overload. This is an important consequence and occurs in a PDA of a large or at least moderate size. The left ventricle (LV)  is forced to accommodate and pump a larger volume of blood. This happens because the blood returning to the  LV through the pulmonary veins and the left atrium, includes not only the cardiac output of the systemic circulation, that is, the amount of blood returning from the tissues to the right heart cavities and then to the pulmonary circulation, but  also blood shunted into the pulmonary circulation through the PDA, which has bypassed the  systemic circulation. Therefore, the LV needs to pump more blood (both the amount of blood that will pass into the systemic circulation plus the shunt that bypasses the systemic circulation through the PDA.

LV volume overload, when large, may cause left heart failure. Increased blood flow through the pulmonary circulation, when there is a large shunt, can cause gradual changes in the pulmonary arterioles resulting in an elevated pulmonary vascular resistance and the occurrence of pulmonary arterial hypertension after some years.

If pulmonary arterial pressure increases to levels equal to or greater than the systemic blood pressure, then the shunt will reverse. That is, the shunt will have an opposite direction, from the pulmonary artery to the aorta (Eisenmenger syndrome). In case of a PDA, if Eisenmenger syndrome occurs, the murmur is only systolic or inaudible (the amount and velocity of the shunting blood is reduced due to a smaller pressure difference between the two communicating arteries). Moreover, the leakage of non-oxygenated blood from the pulmonary artery through the PDA to the descending aorta causes differential hypoxemia and differential cyanosis. This means that a low hemoglobin oxygen saturation and cyanosis are present in the lower extremities, but not in the face, nor in the upper extremities. The reason is that non-oxygenated blood enters the pulmonary artery into the aorta at the site of the PDA, i.e. distal to the origins of the arteries of the head and the upper limbs.

Clinical manifestations of a patent ductus arteriosus (PDA) 

Patients with a small PDA with an audible continuous murmur, do not have any clinical manifestations except from rare cases of infectious endarteritis (infective endocarditis at the site of the abnormal arterial communication). In a moderate or large-sized PDA, patients may have dyspnea (due to left ventricular volume overload and failure or due to pulmonary hypertension) or palpitations, resulting from atrial fibrillation or flutter (the left atrial dilation resulting from the increased pulmonary venous return is a predisposing factor for these arrhythmias).

Physical examination

Cardiac auscultation reveals a continuous murmur best heard on the first or second intercostal space at the left sternal border, with its maximum intensity at end-systole.
In cases of a PDA of a large or moderate size:

  • There are bounding peripheral arterial pulses and a wide pulse pressure (an elevated difference between the systolic and the diastolic pressure), due to runoff of blood into the pulmonary artery during diastole. 
  • The apical impulse of the left ventricle (LV) can be prominent and laterally displaced (due to LV enlargement/ LV volume overload). 
When moderate pulmonary hypertension occurs, the diastolic component of the murmur disappears and only a systolic murmur remains. In severe pulmonary hypertension with a shunt reversal (Eisenmenger's syndrome), differential cyanosis is observed. (Cyanosis of the lower extremities, but not the upper part of the body). 

Diagnostic testing

The ECG in PDA if the L-R shunt is small is normal. If the ductus is large, the ECG shows left ventricular or biventricular hypertrophy .
The chest X-ray in a large PDA shows a prominent
pulmonary artery with increased pulmonary vascular markings. When the shunt is large the chest X-ray usually shows enlargement of the left atrium and left ventricle. 
Εchocardiography in PDA will show in the basal parasternal short axis view, a jet of systolic and diastolic (usually both) retrograde turbulent flow in the pulmonary artery. Left atrial and left ventricular
enlargement will be present only if the shunt is large.

A video ( ECG and echocardiography of a woman with a patent ductus arteriosus)

A 30-year-old woman, who presented for cardiac evaluation, because of a continuous cardiac murmur (grade 3/6, best heard at the second left intercostal space). She was asymptomatic. Physical examination also revealed a wide pulse pressure. Echo showed patent ductus arteriosus of small to moderate size, and normal estimated pulmonary arterial pressure. The PDA was closed with a transcatheter closure device in a specialized center.

Treatment of a PDA

Duct closure is usually recommended, irrespective of the patient's age, if a duct is clinically detectable, i.e. there is a continuous murmur in the left subclavicular area. The reason is to avoid long-term complications, such as endarteritis (which is also possible with a small ductus), or if the 
ductus is of a moderate to large size, arrhythmias, left ventricular failure or pulmonary hypertension. Transcatheter device closure is usually preferred and feasible for ducts with a diameter up to 14 mm. If transcatheter closure is not feasible, then surgical closure is undertaken. Before repair of large ducts, the presence of severe pulmonary vascular disease should be excludedPulmonary hypertension is not a contraindication to surgical or transcatheter PDA closure at any age if cardiac catheterization demonstrates that shunt flow is still predominantly left to right and that severe pulmonary vascular disease is not present.

LINK: Cardiology book- Table of contents

Bibliography and links 

Deri A, English K. EDUCATIONAL SERIES IN CONGENITAL HEART DISEASE: Echocardiographic assessment of left to right shunts: atrial septal defect, ventricular septal defect, atrioventricular septal defect, patent arterial duct. Echo research and practice 2018;5(1):R1-R16.

Rao PS, Harris AD. Recent advances in managing septal defects: ventricular septal defects and atrioventricular septal defects  F1000Res 2018;7:498.

Savis A, Simpson J. Echocardiographic approach to catheter closure of atrial septal defects: patient selection, procedural guidance and post-procedural checks.

Lam JY, Lopushinsky SR, Ma IW, Dicke F, Brindle ME. Treatment Options for Pediatric Patent Ductus Arteriosus. Chest. 2015;148(3):784-793

Congenital heart disease. A concise introduction (overview)

Congenital heart disease. A concise overview

This chapter is a brief, general introduction to congenital heart disease. The diagnosis and treatment of specific congenital heart defects will be discussed in other chapters.

Definition and causes of congenital heart disease

Congenital heart disease includes cardiac lesions that are present from birth. The most common congenital defects in humans are congenital heart defects. The overall incidence of congenital heart disease is about 1 in 100 infants (live births). The incidence of moderate to severe congenital heart disease is approximately 6/1000 infants.
Remarkable improvement in outcomes for patients with congenital heart disease has occurred over the last 50 years, because of the progress in the early diagnosis and in the development of surgical or catheter-based treatment. This has resulted in a growing population of adults with congenital heart disease (approximately 85% of all newborns with congenital heart disease will reach adulthood). As a result, the number of adults with congenital heart disease is larger than the number of children with such disease.
Congenital heart disease usually results from the abnormal embryonic development of a normal cardiac structure or failure of a structure to progress beyond a certain stage of embryonic development.The causes of congenital heart disease are multiple, genetic and environmental factors affecting cardiac development in the uterus. Genetic causes include gene mutations and chromosomal anomalies. Environmental factors include viral infections in pregnancy (such as rubella), alcohol abuse during pregnancy, effects of certain drugs during pregnancy. In most cases, the cause of a congenital heart defect in a given patient is not known.
[The term " syndrome" will often be encountered in this chapter, and notably, although every doctor understands its meaning, some cannot give its exact definition. A definition of "syndrome" is a combination of symptoms, or abnormal clinical or laboratory findings that constitute a distinct clinical picture because they result from a single cause or because they very commonly occur together and have a linked etiology or pathophysiology.]

Some known causes of congenital heart disease include:

Fetal alcohol syndrome (resulting from alcohol abuse by a pregnant woman, it is associated with cardiac defects, but also non-cardiac defects, such as microcephaly, micrognathia, and growth retardation).
Maternal rubella [it can cause patent ductus arteriosus (PDA) and pulmonary stenosis and also non-cardiac lesions such as microcephaly, cataracts, and deafness]
Maternal systemic lupus erythematosus (it can cause fetal complete heart block).
Many genetic defects are associated with congenital heart disease, including:
Marfan syndrome caused by a gene mutation (it is associated with aortic dilatation and aortic regurgitation, mitral valve prolapse and regurgitation). 

Holt-Oram syndrome, also caused by a gene mutation (autosomal dominant), which is characterized by an atrial septal defect combined with skeletal anomalies of the upper extremities, such as a short thumb, or a thumb with 3 phalanges or a short antebrachium.
William's syndrome, a genetic disorder characterized by distinctive facial features ("elfin facies"), cardiovascular defects such as supravalvar aortic stenosis and other features such as neonatal hypocalcemia and later in life mild mental retardation is evident, usually with a friendly talkative personality. The inheritance is autosomal dominant.

Examples of chromosomal anomalies associated with congenital heart disease are: 
Turner syndrome (XO) is the condition in which a female is partly or completely missing an X chromosome. It is associated with coarctation of the aorta, congenital aortic stenosis and atrial septum defect (ASD).
Trisomy 21, also called Down syndrome (it is associated with endocardial cushion defects, atrial septal defect of the ostium primum type, ventricular septal defect).

General classification of congenital heart defects

Congenital heart lesions can be classified as acyanotic (defects that do not cause cyanosis) or cyanotic (defects that cause central cyanosis due to a right- to- left shunt). Cyanosis is a blue discoloration of the mucous membranes or the skin caused by an increased amount of reduced hemoglobin (hemoglobin not combined with oxygen). Central cyanosis occurs when the circulation is mixed as a result of a right-to-left shunt (pathologic flow of unoxygenated blood from a right-sided cardiac chamber to a left-sided one). 

Acyanotic congenital heart defects include:

Ventricular or atrial, or other cardiac communications with left-to-right shunting such as: ventricular septal defect [ An opening in the ventricular septum. The most common type of congenital heart disease encountered in children]
atrial septal defect [An opening in the atrial septum.The most common congenital heart defect encountered in adults, excluding mitral valve prolapse and bicuspid aortic valve]
partial anomalous pulmonary venous return, [ One or more of the pulmonary veins connect to the superior vena cava or to the right atrium.This condition has many of the physiologic characteristics of an atrial defect and it is also often associated with such a defect (in 80-90% of cases).]
patent ductus arteriosus (PDA) [PDA is the second most common congenital heart defect encountered in adults (after ASD) It is a persistent communication between the descending aorta and the left pulmonary artery at the level of the left subclavian artery. A characteristic sign usually present is a continuous murmur (heard in both systole and diastole) which is best heard on the area under the left clavicle]

Congenital abnormalities of the heart valves and great vessels, e.g:congenital aortic stenosis due to a congenital bicuspid aortic valve
[An aortic valve with two cusps instead of three. Studies have reported an incidence of about 0.5-2 % in the general population. In many- but not all- cases the valve may have a dysfunction, stenosis or regurgitation]coarctation of the aorta, [This is usually a narrowing of the descending aorta just distal to the origin of the left subclavian artery, caused by an indentation protruding in its lumen opposite to the entry of the ductus arteriosus, so-called juxtaductal aortic coarctation. Much less commonly there is an elongated, narrowed segment of the proximal descending thoracic aorta that can also involve the arch. Aortic coarctation is often associated with a bicuspid aortic valve and usually it is diagnosed in childhood because of hypertension or a heart murmur.]
congenital subvalvular aortic stenosis [This is a stenosis of the left ventricular outflow tract caused by a discrete fibrous or fibromuscular membrane, or a diffuse, fibromuscular, narrowing of the left ventricular outflow tract (like a narrow tunnel), or rarely accessory tissue on the basal anterior mitral leaflet, or an anomalous chordal attachment of the mitral valve]
 or supravalvular aortic stenosis  [A localized or diffuse narrowing of the ascending aorta distally to the superior margin of the sinuses of Valsalva, which may occur sporadically, as a manifestation of elastin arteriopathy, or as a manifestation of Williams syndrome]
pulmonary stenosis [This term is used for an obstruction (narrowing) to the right ventricular outflow, that may be located at the valvular, subvalvular, or supravalvular level. The most common form is valvular pulmonary stenosis]
congenital mitral stenosis [due to a parachute mitral valve where all chordae tendinae are connected to a single papillary muscle, congenitally dysplastic mitral valve with fused commissures, hypoplastic (small) mitral annulus or a double orifice mitral valve, or mitral stenosis due to the presence of a supravalvular ring].
 Other lesions such as 
Congenital abnormalities of the coronary arteries.
Congenitally corrected transposition of the great arteries [A rare congenital disorder, where the ventricles are in a reversed position, i.e. the right ventricle is in the position of the left ventricle, receiving blood from the left atrium and ejecting blood into the aorta, whereas the left ventricle is receiving blood from the right atrium and ejecting it into the pulmonary artery. This condition is usually diagnosed late in childhood or in early adult life, with the patient presenting with complete heart block or heart failure due to the decompensation of the right ventricle which is the systemic ventricle in this condition, supporting the systemic circulation]

Cyanotic congenital heart defects include :

The two most common in order of frequency are 
Tetralogy of Fallot (TOF) [ It is the constellation of four findings: right ventricular outflow obstruction, a large subaortic ventricular septal defect, an overriding aorta, and right ventricular hypertrophy. Frequently an atrial septum defect may coexist and then the condition is called pentalogy." Common manifestations of TOF include cyanosis, clubbing, dyspnea on exertion, hypoxic spells and squatting ]
Complete transposition of the great arteries (TGA) [ The reversal of the relation of the aorta and pulmonary artery to the ventricles, i.e the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. The common classic type of complete TGA is called d -transposition, with the aorta located anteriorly and to the right of the pulmonary artery. In cases of TGA where the aorta lies to the left of the pulmonary artery, the condition is called l -transposition.) Because in complete TGA the systemic and the pulmonary circulation are two separate circuits, defects that permit a communication of the two circulations always coexist, such as an atrial septum defect, a patent foramen ovale, a ventricular septum defect or a patent ductus arteriosus). The presence of such a communication is necessary for survival. ]
Less common malformations such as: 
Pulmonary atresia, 
Hypoplastic left heart, 
Ebstein anomaly with an ASD  [In Ebstein anomaly there is an inferior apical displacement of the septal and posterior leaflets of the tricuspid valve into the right ventricle. This results in an "atrialized" part of the right ventricle, i.e. a part of the ventricle which has become a portion of the right atrium because of the apical displacement of the tricuspid valve. The remaining right ventricle below that part is small and often dysplastic. The anterior leaflet of the tricuspid valve is large and has a sail-like appearance. Among the patients with Ebstein anomaly, 50% have a communication between the atria, i.e. a patent foramen ovale or a secundum atrial septal defect. Another abnormality that can coexist in patients with Ebstein's anomaly is Wolff-Parkinson-White syndrome since 25% of these patients have one or more accessory pathways of atrioventricular conduction].

Patients with congenital heart defects are divided into three categories according to the surgical status:
unoperated, surgically palliated (patients that have undergone operations that partially improve their condition without complete correction of their defect) or physiologically repaired (complete or near-complete surgical repair of the defect). 

General problems and complications in patients with congenital heart disease

Patients with congenital heart disease can develop various symptoms and complications. In adults with congenital heart disease, there are certain symptoms, particularly progressive dyspnea on exertion and syncope, that should prompt a thorough evaluation.
Arrhythmias present a common problem in adults with congenital heart disease. Arrhythmias in these patients often originate near the myocardial scars of previous surgical operations. The most common arrhythmias that occur, are supraventricular arrhythmias, such as atrial flutter or atrial fibrillation. 
Ventricular tachycardia (VT) may occur in adults with congenital heart disease as a late complication of prior ventriculotomy or patching of a ventricular septal defect. VT is an important arrhythmia because it can cause sudden death. In adults with corrected tetralogy of Fallot (TOF) the incidence of ventricular arrhythmias is  0.5% -5 %. Risk factors for the occurrence of ventricular arrhythmias in such patients include an older age at the time of surgical repair,  a significantly prolonged QRS interval (>180 ms) and significant dilation of the right ventricle.
Pulmonary hypertension is a common complication of certain congenital heart defects. There are two possible causes of pulmonary hypertension, depending on the type of congenital heart disease:
1. Pulmonary hypertension as a result of  pulmonary venous
hypertension due to elevated left-sided filling pressures, 
2. Pulmonary hypertension as the result of a left to right shunt, i.e an abnormal communication between the left and right heart chambers with blood flow from a left heart chamber towards a right heart chamber. This increases flow in the pulmonary arterial circulation and can result over the years in pulmonary arterial hypertension (PAH).
Shunts proximal to the tricuspid valve such as atrial septal defects or partial anomalous pulmonary venous return uncommonly result in pulmonary hypertension ( about 15 % of cases), whereas shunts distal to the tricus­pid valve, for example a large ventricular septal defect, more commonly cause pulmonary hypertension

Left to right (L-R) shunt lesions are common types of congenital heart disease. As a general rule, a significant L-R shunt is  characterized by a ratio of pulmonary flow to systemic flow 
1.5 : 1, but this rule may not apply to adults if pulmonary hypertension has developed. In such a case, the elevated pressures on the right side and the reduced right ventricular compliance gradually cause the reduction of the L-R shunt flow. When pulmonary arterial hypertension becomes severe, the L-R shunt may reverse, resulting in the development of a right to left (R-L) shunt, i.e. an abnormal flow of desaturated blood from a right heart chamber to a left heart chamber. This causes a reduction in the hemoglobin-oxygen saturation of the arterial blood (arterial desatura­tion) with the development of cyanosis, a condition called Eisenmenger syndrome.
Cyanosis in congenital heart disease occurs when persistent mixing of desaturated blood to arterial blood, due to a R-L shunt, results in hypoxemia (reduced oxygen content of the arterial blood and a fall in hemoglobin saturation with oxygen). In such cases, the body has some adaptive mechanisms to increase oxygen delivery to the tissues, such as a rightward shift in the oxyhemoglobin dissociation curve, a rise of the hematocrit (secondary erythrocytosis), and a rise in cardiac output. Chronic hypoxemia and erythrocytosis in patients with cyanotic congenital heart disease can cause the development of various complications, such as: 
 hematologic (hyperviscosity, iron deficiency, and bleeding diathesis)
 neurologic (possible complications include cerebral hemorrhage or paradoxical cerebral embolization from a venous thrombus entering the systemic circulation through a congenital heart defect)
renal (proteinuria, hyperuricemia, or renal failure)
pulmonary (pulmonary in situ arterial thrombosis, or pulmonary hemorrhage)
and rheumatologic complications (gout and hypertrophic osteoarthropathy causing arthralgias. Another musculoskeletal manifestation of cyanotic congenital heart disease is digital clubbing, which is an enlargement of the distal segments of the fingers. Clubbing is usually an indication of an underlying disease such as a cyanotic congenital heart disease, a chronic pulmonary disease or lung cancer, infective endocarditis, inflammatory bowel disease, cirrhosis of the liver. But there are also cases where clubbing is idiopathic or hereditary without any underlying disease.)
Symptoms of hyperviscosity include headaches, dizziness, visual disturbances, altered mentation, fatigue and paresthesias.
Another important issue related to congenital heart disease, is pregnancy in a woman with congenital heart disease. The presence of congenital heart disease is associated with an increased risk for peripartum complications. However, maternal congenital heart disease is not a contraindication to pregnancy unless certain high-risk features are present, such as pulmonary hypertension, cyanosis, decompensated heart failure, aortic aneurysm, severe valve disease.

LINK: Cardiology book- Table of contents

Bibliography and links 

Triedman JK, Newburger JW. Trends in Congenital Heart Disease.The Next Decade. Circulation. 2016;133:2716-2733

 ESC Guidelines for the management of grown-up congenital heart disease (new version 2010)  European Heart Journal (2010) 31, 2915–2957

Congenital Heart Disease in Children

Guidelines for Evaluation and Management of Common Congenital Cardiac Problems in Infants, Children, and Adolescents
A Statement for Healthcare Professionals From the Committee on Congenital Cardiac Defects of the Council on Cardiovascular Disease in the Young, American Heart Association

Canadian cardiovascular society guidelines on the management of adult congenital heart disease 2009

Prosthetic heart valves ( a concise overview)

Prosthetic heart valves

There are two main types of prosthetic heart valves, mechanical valves which are durable but require chronic anticoagulation
because of thrombogenicity and biological valves which are less durable, but also less thrombogenic. Biological valves do not require lifelong anticoagulation (unless there are other reasons for anticoagulation, such as atrial fibrillation).

The hemodynamic characteristics of a prosthetic heart valve (flow velocity, peak pressure gradient, mean pressure gradient) are influenced by the type of the valve and the diameter of the valve ring (smaller diameter entails a higher peak flow velocity and pressure gradient). An echocardiogram should be performed after the implantation of a prosthetic valve so that the findings can be used for future comparison.

Mechanical heart valves

Mechanical heart valves consist of a sewing ring and the occluder (the moving part of the valve which moves from the opening to the closing position at the appropriate phases of the cardiac cycle). Bileaflet mechanical valves, the type of mechanical valves currently used, have two occluders (leaflets), while single tilting disk and cage-ball valves have one occluder ( a disk, or a ball) respectively.
Tilting disk valves: They are classified in single and double tilting disk (bileaflet) valves. Nowadays mainly double disk (bileaflet) valves are used.

Single tilting disk valves (Medtronic-Hall, Omniscience, Bjork-Shiley, 
Lillehei-Kaster) consist of a ring and a disk, that shifts between the opening position and the closing position, supported by metal struts. In the opening position the disc forms with the plane of the ring an angle of 60-80 degrees.

For a single tilting disk mechanical valve at the aortic position, the peak blood velocity is usually in the range of 1.6-3.3 m /sec. At the mitral position, the peak velocity is usually 1.4-1.7 m /sec.

The bileaflet (double disk) valves (e.g. St Jude Medical, Carbomedics, Sorin Bicarbon, Medtronic Open Pivot, ATS valve, On-X) consist of two semi-circular pyrolytic carbon disks attached to the ring of the valve with special hinges. At the opening position, each disc forms an angle of 75-90 degrees. (This is a general description, but there are some differences in certain technical details between valve types).

The bileaflet valves are the mechanical valves currently used because they have better hemodynamic characteristics ( lower transvalvular gradients) and low thrombogenicity in comparison to other types of mechanical cardiac valves, such as cage ball or tilting single disk valves

 For a double disk mechanical valve in the aortic position the peak blood velocity is usually 2-3 m /sec (up to 3.3 m /sec for valves with a smaller diameter) and the peak pressure gradient 16-45 mm Hg.(Higher values apply to a small diameter valve ring: 19 or 21 mm). Of course, these limits are approximate and not absolute.

For a double-disk mechanical valve at the mitral position, the mean pressure gradient is usually 2.5-7 mm Hg and the peak velocity is 1.1-2 m /sec.

Small deviations may be observed from the above flow velocity measurements and pressure gradients. An echocardiogram should be performed after the implantation of a prosthetic valve so that the measurements can be used for future comparison.

What do these two images show?

The top image shows a 3 dimensional (3D) echocardiogram of a mechanical bileaflet prosthetic valve in the mitral position viewed from the left atrial side in diastole with the leaflets in the open position. Normal opening of the valve can be seen. The lower image shows the same valve in systole (closed position). 1. sewing ring of the prosthesis/ 2. leaflets

The Cage-Ball Valve (Starr-Edwards) is an old valve type, which had been in use for twenty-five years, but nowadays it is not being implanted. It consists of a ball of silicone, swinging in a cage of metal alloy (cobalt-chromium). On the valve base, there is a sewing ring that serves to secure the valve to its position. When the valve opens, the ball moves away from the ring and blood flows around it, while on closing the ball fits onto the ring, preventing blood regurgitation. This valve is bulky (unsuitable for patients with a small aortic annulus or small left ventricle). Turbulent flow also occurs around the sphere. Due to the above, a higher pressure gradient is generated compared to other valves. In addition, turbulent flow causes endothelial injury, so this valve is more thrombogenic.  On auscultation of the patient, multiple opening sounds are heard due to the impact of the ball on the cage supports. There is also a metallic closing sound.

Bioprosthetic heart valves (Biological tissue valves or bioprostheses) 

Bioprosthetic valves (bioprostheses) can be heterografts or xenografts (valves made of animal tissue), which are composed of
porcine, bovine, or equine tissue (valvular or pericardial), or homografts, which are preserved human aortic valves. In cardiac auscultation, normally functioning bioprosthetic (biological) valves do not differ from normal native valves. There are several types of bioprosthetic valves: .
Heterografts or XenograftsHeterografts include stented and stentless biological valves. In stented valves, the biological valve tissue is mounted on a rigid stent (plastic or metallic), also called sewing ring, covered with fabric. Conversely, stentless bioprostheses do not include a stent, thus they use the patient’s native aortic root as the valve stent. 
 Heterografts are: 1) Porcine valves properly suited to a suture ring made of synthetic material. Such valves are: Carpentier-Edwards, Hancock II and Mosaic (Medtronic). With echocardiography, for the Carpentier-Edwards valve at the mitral position, the expected peak velocity is about 1.5-2 m /sec and the expected mean pressure gradient of 5-9 mmHg. In the aortic position, the expected peak velocity is 2-3 m /sec and the expected mean pressure gradient  8-20 mmHg.

A more recent development is the introduction of stentless porcine valves. The absence of a stent enables implantation of a larger valve for a given native annulus size, resulting in a larger effective orifice area (EOA) and a lower transvalvular pressure gradient, which is an advantage of these valves. Such are: Edwards Prima Plus, Medtronic Freestyle, and Toronto SPV (St. Jude Medical.)

 2) Valves made of bovine pericardium. These include the following: Perimount series valves (Edwards LifeSciences). and Ionescu-Shiley, which is no longer produced.
Pericardial valves are also two valve types used in transcatheter aortic valve implantation (TAVI): SAPIEN XT (Edwards LifeSciences) made of bovine pericardium and CoreValve (Medtronic) made of porcine pericardium. The valves used for TAVI are trileaflet bioprosthetic valves mounted in a wire mesh stent. Delivery of the valve is performed over a catheter and the stent is expanded in the position of the aortic valve. TAVI can be performed with a catheter advanced from the femoral artery in retrograde fashion across the aortic valve, or from a small thoracotomy with the catheter passed through the apex of the left ventricle and advanced across the aortic valve. This procedure is used for calcific aortic stenosis with the native valve being compressed but remaining in place. TAVI is indicated in patients with severe symptomatic aortic stenosis who have a high risk of adverse surgical outcomes due to comorbidities. Possible complications include stroke, vascular complications (at the entrance site at the femoral artery), and paravalvular regurgitation

Homografts or allografts
Preserved aortic valves from human cadavers.
Usually taken 24 hours after the donor's death, they are sterilized by antibiotics and maintained at a temperature of -196 ° C. The recorded Doppler velocities are approximately the same as those of native aortic valves.
Autograft  (Ross operation)
Pulmonary autograft is the patient's own pulmonary valve implanted to replace a pathologic aortic valve, during a Ross operation. The pulmonary autograft consists of the pulmonary valve with its ring and a small part of the main pulmonary artery. The aortic valve and the aortic root are replaced with the autograft, to which the coronary arteries are then implanted. Subsequently, a pulmonary allograft (cadaveric graft) is implanted in place of the pulmonary valve. Advantages of this operation are that the autograft placed in the aortic position has a very good hemodynamic behavior and better durability than other biological valves. The disadvantage is that it is a technically difficult procedure that requires a long duration of extracorporeal circulation and is only performed in a few cardio-surgical centers with experience.

Stentless prosthetic valves

These are prostheses that do not contain a prosthetic ring and include stentless heterografts (e.g stentless porcine valves), aortic homografts, and the pulmonary autografts. These have lower transvalvular gradients that the other types of prosthetic heart valves.

Selection of the type of prosthetic heart valve

The patient should be informed about the advantages and disadvantages of each option and the desires of the well-informed patient are also taken into consideration, as well as the following important factors. Mechanical valves have greater durability, but need lifelong anticoagulation, whereas bioprostheses are less durable, but have the advantage of a lower thrombogenic potential and do not need lifelong anticoagulation.
In favor of a mechanical prosthetic valve are the following:
Age< 65 with a long life expectancy (> 10 years on the basis of age and the presence or absence of serious comorbidities), 
No contraindications for anticoagulation, or a patient already receiving anticoagulation treatment (a patient that already has a mechanical prosthesis and needs a second prosthetic heart valve).
In favor of a biological prosthetic valve are the following:
Age >65, (more specifically for a valve in the aortic position age> 65 and for a valve in the mitral position age > 70) or a limited life expectancy,
  a contraindication for anticoagulation, 
or a woman of childbearing age who desires pregnancy.
Age limits are not absolute and they can be further refined, depending on the position if the prosthetic valve:
In the mitral position, a mechanical valve should be generally preferred in patients of age <65, and both valve types (mechanical or bioprosthetic) are acceptable in patients between 65-70 years.
In the aortic positiona mechanical valve should be generally preferred in patients of age <60, and both valve types (mechanical or bioprosthetic) are acceptable in patients between 60-65 years.

Antithrombotic treatment in patients with prosthetic heart valves

Bioprosthetic valves:

Bioprosthetic (biological) valves are clearly less thrombogenic than mechanical ones, so they do not necessarily need anticoagulation. However, there is a risk of embolism during the initial postoperative period (mechanism: thrombus production on the prosthetic valve support ring). According to the guidelines in patients with a bioprosthetic valve in the mitral or tricuspid position, it is a good practice (with a category IIa-not absolute- indication) to administer anticoagulation with a vitamin K antagonist (acenocoumarol or warfarin) for the first 3 months after valve implantation. Postoperatively heparin (unfractionated or low molecular weight) is initially administered and treatment with a vitamin K antagonist (VKA) is also initiated. When the INR reaches therapeutic levels (2-3) heparin is discontinued and oral anticoagulant treatment is continued (with INR 2-3) for 3 months After 3 months, the risk of thromboembolism is much lower. (INR = international normalized ratio). Therefore, anticoagulation with VKA is discontinued, and permanent antithrombotic treatment with aspirin 80-100 mg (or clopidogrel 75 mg) per day is initiated.
Oral anticoagulation using a VKA should also be considered for the first 3 months after surgical mitral or tricuspid valve repair (a class IIa indication)
 After surgical implantation of a bioprosthetic valve at the aortic position, because at this position there are higher blood flow velocities resulting in less risk of thrombosis, guidelines recommend administering only low dose aspirin  (eg 80-100 mg daily) for the first 3 months after surgery. This has a Class IIa indication.
However, guidelines allow the option to give these patients (with an aortic bioprosthesis) in the first 3 months a VKA instead of aspirin but with a  class IIb indication ( a "weak" indication).
Exception: In patients with a bioprosthetic valve that also have other risk factors for thromboembolism (such as: a previous embolic episode, atrial fibrillation, or severe left ventricular systolic dysfunction with an ejection fraction  35% or a hypercoagulable state), anticoagulation with  INR 2-3 is administered lifelong (and not just for the first 3 months). This is an absolute (class I) indication for permanent anticoagulation.
After transcatheter aortic valve implantation (TAVI), dual antiplatelet therapy is administered for the first 3-6 months. This is followed by lifelong single antiplatelet therapy in patients who do not need oral anticoagulation for other reasons. In case of TAVI, where an additional thromboembolic risk factor (atrial fibrillation, left ventricular systolic dysfunction, hypercoagulability) is also present, a vitamin K antagonist (VKA) is permanently administered with target INR 2-3, while aspirin 80-100 mg, or clopidogrel 75 mg daily is given during the first year and then it is discontinued

Mechanical prosthetic heart valves

Lifelong oral anticoagulation with a vitamin K antagonist (VKA) is recommended for all patients with mechanical prosthetic valves (this is an absolute-class I-recommendation). Note that the new oral anticoagulants (NOACs) are not used in patients with mechanical cardiac valves. The target INR depends on the thrombogenicity of the type of the mechanical valve prosthesis and patient risk factors (such as mitral or tricuspid valve replacement, previous thromboembolism, atrial fibrillation, mitral stenosis of any degree, severe left ventricular systolic dysfunction with EF <35%).
Thrombosis and thromboembolism risks are greater with a mechanical valve in the mitral than in the aortic position.

If the patient has a mechanical valve prosthesis of low thrombogenicity and no other risk factors for thromboembolism the target INR is around 2.5, but if 1 or more of the other risk factors are present, then the target INR is around 3.

Mechanical heart valves with a low thrombogenicity are most bileaflet valves: St Jude Medical, Carbomedics, Sorin Bicarbon, Medtronic Open-Pivot, ATS, On-X (all these are mechanical bileaflet valves), and also Medtronic Hall (a single disk valve).

If the patient has a mechanical valve prosthesis of medium thrombogenicity and no other risk factors for thromboembolism the target INR is around 3, but in the presence of 1 or more of the other risk factors the target INR is around 3.5
Mechanical valves of medium thrombogenicity are some other bileaflet valves with insufficient data.

If the patient has a mechanical valve prosthesis of high thrombogenicity and no other risk factors for thromboembolism the target INR is around 3.5, but in the presence of 1 or more of the other risk factors, the target INR is around 4.
Mechanical valves of high thrombogenicity are: the ball-cage valve (Starr-Edwards) and most single disk valves (with the exception of Medtronic Hall) such as Lillehei-Kaster, Omniscience, Bjork-Shiley and other single tilting-disc valves.
Good management of anticoagulation is important since a high variability of the INR is a strong independent predictor of
reduced survival after heart valve replacement with a mechanical prosthesis.

The addition of low-dose aspirin (75-100mg/day) to VKA should be considered if thromboembolism occurs, despite an adequate INR (IIa C)

 In cases when VKA treatment should be interrupted, bridging with therapeutic doses of unfractionated heparin (UFH) or low molecular weight heparin (LMWH) is recommended.

Patients with mechanical heart valves undergoing a percutaneous coronary intervention (PCI) 

In patients with mechanical heart valves undergoing a percutaneous coronary intervention (PCI) with stenting, there is a need for a temporary combination of anticoagulant (VKA) and antiplatelet drugs( aspirin, clopidogrel), a situation that increases the risk of bleeding. Guideline recommendations for these patients can be summarized as follows:
Initially triple antithrombotic treatment (VKA+aspirin+clopidogrel) is administered for 1 month (it may be given for up to a maximum duration of  6 months if the patient is considered to have a high thrombotic risk and a low bleeding risk). After the period of triple antithrombotic treatment, dual therapy (VKA+clopidogrel, or VKA+aspirin) follows until up to 12 months after coronary stent implantation. Then antiplatelet treatment is discontinued and the patient continues only VKA (anticoagulation). 
In patients with a high bleeding risk (when bleeding risk is considered as more important than ischemic risk), triple antithrombotic treatment is not given. Then treatment after PCI includes only a period of dual antithrombotic therapy (VKA+ clopidogrel) which can last up to 12 months. After that antithrombotic therapy continues only with the VKA. A high ischemic risk ( a high risk for a subsequent myocardial infarction) is considered to be present in patients presenting with an acute coronary syndrome or having certain characteristics of the coronary lesion (e.g. presence of thrombus, a complex lesion), whereas the bleeding risk is estimated by using the HAS-BLED score.
HAS-BLED stands for:
Hypertension (systolic >160 mmHg) or
Abnormal renal function (creatinine >2.2 or dialysis or renal transplant)

Abnormal liver function (Cirrhosis or Bilirubin >2x Normal or AST/ALT/ALP >3x Normal)
Stroke (history of previous stroke)
Bleeding (
Prior major bleeding or predisposition to bleeding
Labile INR (unstable or high, remains in the therapeutic range for < 60% of the time)
Elderly (> 65 years)
Drugs (medication usage that predisposes to bleeding, such as NSAIDs or antiplatelet drugs)  or

 alcohol(≥ 8 drinks/week)
The presence of each of the above adds 1 point to the score.
A HAS-BLED score of ≥3 indicates high risk for major bleeding ( defined as intracranial hemorrhage, or bleeding requiring hospitalization, or hemoglobin decrease > 2 g/dL, and/or transfusion) 

Clinical and echocardiographic follow-up of a patient with a prosthetic heart valve

In general, emphasis should be placed on informing the patient about proper adherence to anticoagulation and endocarditis prophylaxis.
According to the guidelines of the European Society of Cardiology (ESC) a patient who undergoes a valve replacement requires after 6-12 weeks a complete follow-up examination, including clinical examination (history of possible symptoms, cardiac auscultation to check for the expected auscultatory findings for the type of prosthetic valve and also to check for a possible new cardiac murmur), ECG, chest X-ray, transthoracic echocardiography (TTE) and blood tests. 

Physical examination and cardiac auscultation of a patient with a prosthetic heart valve

Significant abnormal  findings from the physical examination of a patient with a prosthetic heart valve may include a new or changed murmur, muffled valve sounds, or signs indicative of an embolic event (e.g. a neurological deficit in a case of an embolic stroke).
The expected auscultatory findings in patients with a prosthetic valve depend on the type of the valve prosthesis. Normally functioning biological prosthetic valves have the same auscultatory findings as normal native valves. Among the mechanical valves, the bileaflet mechanical valves, which are the type of mechanical valves currently implanted, do not produce an opening sound but only a metallic closing sound. Single-tilting disc mechanical valves produce an opening sound and a closing sound, while the cage-ball valves produce multiple opening sounds, due to the impact of the ball on the cage. On auscultation of the heart, the absence of the expected sounds produced by the prosthetic valves is a pathological finding indicative of limited valve mobility due to thrombosis or tissue hyperplasia.
All mechanical valves in the aortic position additionally produce a characteristic mild systolic ejection murmur. In contrast, the small normal regurgitation of blood (small physiological insufficiency) present in the mechanical valves does not produce a murmur. Therefore, in a patient with a mechanical aortic valve, the finding of a diastolic murmur is a pathological finding, indicating a paravalvular leak (paravalvular regurgitation).

Echocardiography of prosthetic heart valves

The echocardiogram should include measurement of the transvalvular pressure gradient, color Doppler examination to search for a paravalvular regurgitation and assessment of ventricular function.
Echocardiographic findings and measurements within the first few weeks after surgery will serve as a reference for comparison with future findings. A basic parameter is the pressure gradient (pressure difference) across the valve when it is open. The measurement of the peak velocity and the calculation of the peak and mean transvalvular pressure gradient is performed with the continuous wave Doppler. All prosthetic valves have a peak transvalvular velocity which is higher than that of a normal, native valve. They also create a greater pressure gradient than a normal natural valve, given that the latter creates a negligible pressure gradient. As mentioned, depending on the type of prosthetic valve, there are some expected limits for the pressure gradient (some approximate limits have been given above).
Elevated transvalvular velocity and pressure gradient in a prosthetic valve, as compared to the expected values, is observed in cases of: 1) Valve malfunction causing stenosis (thrombus or pannus development, mechanical degeneration and stenosis due to degeneration and calcification of a bioprosthetic valve), 
2) In cases of increased flow through of the valve with no narrowing of the valve (conditions with an increased cardiac output such as hyperthyroidism, anemia or a significant valvular or paravalvular regurgitation). In the case of significant regurgitation at the valve, there is a volume overload of the ventricular cavity located proximally to the valve, resulting in a larger volume of blood passing through the valve when it opens and thus in a higher velocity and pressure gradient.
3) In prosthesis-patient mismatch (PPM), where there is no valve dysfunction, but the valve is small for the patient's body size and circulatory needs. 

Echocardiographic indications of prosthetic valve stenosis

In a prosthetic aortic valve (bioprosthetic or mechanical), indications of a significant stenosis are a peak flow velocity> 4 m / sec, a mean pressure gradient> 35 mmHg, an effective valve orifice <0.8 cm2, and an acceleration time > 100 msec. An indication for a possible stenosis or a moderate stenosis is a peak velocity between 3 and 4, a mean pressure gradient between 20 and 35, an effective orifice between 0.8 and 1.2 and an acceleration time between 80 and 100.  The acceleration time is the time interval between the onset of blood flow through the valve and the peak flow velocity. Apart from the adequacy of valve opening, it is also affected by the heart rate and contractility of the left ventricle. When the shape of the flow signal obtained with the continuous Doppler is triangular with the peak velocity occurring early, this is a sign of normal flow, whereas when it is symmetrical and rounded, this is indicative of stenosis.
In a prosthetic mitral valve (biological or mechanical), a sign of significant stenosis is a peak flow velocity> 2.5 m / sec, a mean pressure gradient ≥ 10 mmHg, 
an effective valve orifice<1 cm2  and a pressure half time (PHT) > 200 msec.
 An indication of a possible stenosis, or moderate stenosis of a prosthetic mitral valve is a peak velocity is between 1.9 and 2.5 / a mean pressure gradient between 6 and 10 / an effective orifice area between 1 and 2 and a PHT between 130 and 200. Apart from valvular function, the PHT is also influenced by left ventricular diastolic function (compliance).

Calculation of the functional orifice area or effective orifice area (EOA) of prosthetic valves 

The functional orifice area or effective orifice area (EOA) of prosthetic valves is calculated with the continuity equation, which is based on the principle that flow in a heartbeat is the same through all areas of the circulation. 
The EOA of a prosthetic aortic valve is calculated with the continuity equation as
CSA LVOT is the cross-sectional area of the LVOT, VTI LVOT the velocity-time integral measured by using pulse wave Doppler in the LVOT, VTI PrAV the velocity-time integral obtained by continuous wave (CW) Doppler through the prosthetic aortic valve. The cross-sectional area of the LVOT is obtained from diameter measurement just proximally to the prosthesis from the parasternal long-axis view.  CSA LVOT = πr= 3.14 x (d/2)2= 0.785 d2, where r is the radius and d is the diameter of the LVOT measured in the parasternal long axis echocardiographic view. Instead of measuring d, the diameter of the sewing ring of the prosthetic aortic valve can be used in this equation as the diameter of the LVOT.
The EOA of a prosthetic valve in the mitral position is calculated as EOA = (CSA LVOT xVTI LVOT )/VTI PrMV,
where VTIPrMV is the velocity-time integral obtained by CW Doppler through the prosthetic mitral valve. 
CSA LVOT = 0.785 d2, where d is the diameter of the LVOT measured in the parasternal long axis echocardiographic view, just proximal to the aortic valve.

Prosthetic valve regurgitation

For the detection and grading of prosthesis regurgitation, the echocardiographic methods and measured parameters used are similar to those used for native cardiac valves.
It is important to distinguish pathologic prosthesis regurgitation from the small physiologic regurgitation usually present in prosthetic valves. Mechanical prosthetic valves have a normal small amount of regurgitation called leakage backflow which has a washing effect against blood stasis and thrombus formation. In contrast to the jets of pathologic regurgitation, the normal leakage backflow jets are short in duration, narrow, symmetric and have a small size. Also in bioprosthetic heart valvesa minor degree of central transvalvular regurgitation is often present
In the case of pathologic regurgitation, the origin of the regurgitant jet should be located to distinguish paravalvular from transvalvular regurgitation. 
Causes of pathologic prosthesis regurgitation include paravalvular regurgitation or pannus both in mechanical and biological valves, calcific degeneration and tear of valve leaflets in bioprosthetic valves, thrombus in mechanical valves. Paravalvular regurgitation is caused by infective endocarditis, calcification or fibrosis of the native valve annulus with poor contact with the suture ring, or suture detachment.Thrombus and pannus can also cause valve stenosis (this is their most usual presentation). The stentless prosthetic valve substitutes can also develop functional central aortic regurgitation as a result of continued dilation of the aortic root.
For the evaluation of prosthetic valve regurgitation, with transthoracic echocardiography (TTE) as well as with transesophageal echocardiography (TEE), obtaining color Doppler images in multiple views and multiple planes is essential.
Acoustic shadowing can obscure regurgitant jets and this is more an issue for prosthetic valves in the mitral than for those in the aortic position.

Grading of a mechanical or bioprosthetic aortic valve regurgitation (central or paravalvular)

An indirect sign is left ventricular (LV) size which in the case of mild aortic regurgitation (AR) is expected to be normal, in moderate AR it will be either normal or mildly increased but in severe AR prominent LV dilation will be present.
Regurgitant color Doppler jet width at its origin expressed as % of the left ventricular outflow tract (LVOT) diameter: the wider the jet the more severe the regurgitation:  Mild regurgitation ≤30 %, moderate between 30 and 60%,  severe regurgitation >60%.
Vena contracta is another useful echocardiographic parameter used to grade valve regurgitation severity. Vena contracta is defined as the narrowest region of a flow jet that occurs at, or just downstream to, the regurgitant orifice (the orifice at the valve where regurgitation occurs).
Vena contracta width in mm: 
mild regurgitation <4,  moderate 4-6, severe regurgitation  >6
Vena contracta area (measured with 3D color Doppler in mm2): 
mild regurgitation <20 moderate 20-40, severe regurgitation  >40
The density of the regurgitant jet examined with continuous wave (CW) Doppler: in mild regurgitation, the jet is incomplete or faint, whereas in moderate or severe regurgitation it appears dense.
The pressure half time (PHT measured in ms) of the regurgitant jet This is the time from the onset of the regurgitant flow to the point the pressure gradient (=4xvelocity2between the aorta and the left ventricle becomes half of its initial value. It is calculated by the machine from the CW Doppler signal of the regurgitant flow when you trace the slope of the signal. The more severe the regurgitation the quicker the decline of the pressure difference (pressure gradient) between the two communicating cavities (aorta and left ventricle) and thus the smaller the value of the PHT: mild regurgitation PHT >500 ms, moderate regurgitation 200-500 ms, severe regurgitation <200 ms.
Another useful index is the diastolic flow reversal in the descending aorta, assessed with PW Doppler from the suprasternal echocardiographic view: In a mild regurgitation, this is absent or brief early-diastolic, whereas in severe regurgitation there is a prominent holodiastolic flow reversal with an end-diastolic velocity >20 cm/s. In moderate regurgitation, the findings are intermediate between those two situations.
Left ventricular outflow to right ventricular outflow ratio. This is calculated by obtaining the PW Doppler signal of the systolic flow in the left ventricular and right ventricular outflow tract and expressed as the ratio of the respective stroke volumes or velocity-time integrals. The greater the aortic regurgitation (AR), the greater the ratio of LV outflow/RV outflow. This happens because AR causes an increased stroke volume of the left ventricle due to volume overload of the ventricle, which has to eject not only the effective forward flow of blood that will reach the systemic circulation but also the volume of blood that regurgitates during diastole.
Thus in severe AR this ratio is increased (>1.8).

Grading of a mechanical or bioprosthetic mitral valve regurgitation (central or paravalvular)

Vena contracta width in mm (for the definition of vena contracta see above): mild regurgitation  < 3, moderate with a vena contracta width between 3 and 6 and severe regurgitation  ≥ 6 mm.
The color flow jet area can also provide an indication but it underestimates regurgitation severity when the jet is not central but eccentric, impringing on the interatrial septum or the wall of the left atrium. When we are dealing with a relatively central jet, mild regurgitation is characterized by a small jet size (usually < 4 cm2 or
<20% of left atrial area), whereas severe mitral regurgitation (MR) is characterized by a large jet (usually >8 cm2 or >40% of left atrial area) 
The size of the zone of flow convergence, which is viewed with color Doppler as a hemispheric area of blood at the left ventricular side, accelerating towards the regurgitant orifice: mild MR is characterized by a nonvisible or minimal zone of flow convergence, whereas severe MR is characterized by a large flow convergence zone.
MR jet density assessed with CW Doppler: mild MR is characterized by an incomplete or faint CW signal of the regurgitant jet, whereas severe MR by a dense CW signal.
MR Doppler signal contour assessed with CW Doppler: in mild MR it has a parabolic shape, whereas in severe MR the CW signal is triangular and early peaking.
The PW Doppler signal of pulmonary venous flow in mild MR demonstrates dominance of the systolic wave (versus the diastolic wave), in moderate MR there is systolic blunting (the height of the systolic wave is reduced), and in severe MR there is systolic flow reversal (a negative systolic flow wave).
A quantitative parameter is the effective regurgitant orifice area  EROA (mm2 ), which in moderate MR is between 20 and 40 and in severe MR ≥40 mm2 (0.4 cm2)
Another quantitative parameter is the regurgitant volume RV  (mL/beat) which in moderate MR is between 30 and 60 and in severe MR  >60. These two quantitative parameters of MR severity are calculated by using the proximal isovelocity surface area  (PISA) method (see chapter on mitral regurgitation, link Mitral regurgitation. Diagnosis, echocardiography and management.)
The regurgitant fraction= regugitant volume/stroke volume in moderate MR is 30-50 % and in severe MR >50 %
Indirect signs of the severity of MR that should not be neglected:
LV size : In mild MR it is expected to be normal, in moderate MR the LV is expected to be normal or mildly dilated and in severe MR it should be clearly dilated.
Left atrial (LA) size: in moderate MR it is usually normal or mildly dilated and in severe chronic MR left atrial dilation is prominent (but in cases of acute severe MR the LA size can be normal, because it did not have the time to enlarge).
Pulmonary hypertension is generally present in cases of severe MR 
( systolic pulmonary arterial pressure SPAP ≥50 mm Hg at rest and ≥60 mm Hg at exercise).

Useful videos !! (LINKS)
Assessment of Prostheses in Echocardiography 123sonography (Prof Thomas Binder)

Prosthetic Valve Assessment (William A. Zoghbi, MD) DeBakey Institute For Cardiovascular Education & Training

Prosthetic valve echocardiography 
(Dr. John Chambers, Youtube channel MEDICAL IMAGING)

A normally functioning bileaflet mechanical prosthetic valve in the mitral position (3D echo)
From you tube channel LondonCardioClinic

Prosthetic valve complications

Prosthetic valve thrombosis

There is an increased risk in case of inadequate anticoagulation in a patient with a mechanical prosthetic valve (INR significantly lower than target value) and mechanical prosthetic valves in the mitral position, or the older types of mechanical prosthetic valves (cage-ball, single leaflet). Clinical presentation can be with embolization, e.g. an embolic stroke, or acute limb ischemia, or acute valvular dysfunction causing acute pulmonary edema, or sudden death.
On physical examination diminished intensity of valve sounds may be present. On echocardiography or fluoroscopy, there is a reduced movement of the valve leaflets. There is also an increased transvalvular gradient on echocardiography.
Treatment: Anticoagulation with heparin. If the thrombus is <5 mm on echocardiography, then anticoagulation may suffice. If the thrombus is > 5 mm then apart from heparin, thrombolysis, thrombectomy or valve replacement will be required. Generally, for thrombosis of left-sided prosthetic heart valves, surgical treatment with valve replacement is indicated, unless there is a prohibitive surgical risk or a small thrombus. For thrombosis of a right-sided prosthetic valve, the treatment of choice is thrombolysis (fibrinolysis). Surgery is indicated if thrombolysis is unsuccessful 24 hours after discontinuation of the infusion.


An embolization in a patient with a prosthetic heart valve more commonly manifests as an ischemic stroke (cerebral infarction).
In patients with prosthetic valves presenting with peripheral embolization, endocarditis should also be considered.
Risk factors include: atrial fibrillation, left ventricular systolic dysfunction, age > 70 years, mitral prostheses, cage-ball valves, the presence of more than 1 prosthetic heart valve. If there are clinical findings suggesting a stroke, a brain computed tomography (CT) should be performed immediately to exclude an intracranial hemorrhage ( in case of an intracranial hemorrhage anticoagulation is withheld and specialist help from a neurologist or neurosurgeon is also needed).

Patient-prosthesis mismatch (PPM)

PPM is a situation where the problem is not prosthetic valve dysfunction, but a small prosthetic valve for patient needs. The effective orifice area (EOA) of the valve is indexed to body surface area (BSA), i.e. it is divided by the BSA. In a prosthetic valve in the aortic position when EOA / BSA0.85 cm2/m2, then there is only mild or no PPM. On the contrary, when EOA / BSA ≤ 0.65 cm2/mthen there is considerable PPM and significant stenotic phenomena. Intermediate values below 0.85 but over 0.65 cm2/m2  suggest a moderate degree of patient-prosthesis mismatch (PPM).
In a case of a prosthetic valve at the mitral position, when 
EOA / BSA >1.2 cm2/m2, there is only mild or no mismatch between prosthetic valve and patient. Conversely, when EOA / BSA ≤ 0.9 cm2/m2, then there is considerable PPM and significant stenosis. Intermediate values, below 1.2 but over 0.9 cm2/m2  indicate a moderate degree of PPM.
Several studies link PPM with a decreased postoperative cardiac index, a worse New York Heart Association (NYHA) functional class, a higher likelihood of late adverse events and shorter mean patient survival.

Haemolysis in patients with prosthetic heart valves

A mild haemolysis is common in patients with mechanical prostheses (even with normal prosthetic valve function). Severe haemolysis is not common and is usually a result of prosthetic valve dysfunction (regurgitation, dehiscence, infection).
Blood tests in case of haemolysis show anemia (decreased hemoglobin and hematocrit), increased levels of lactate dehydrogenase (LDH) and reticulocytosis.
Treatment: Administration of folic acid and ferrous sulphate may be needed to increase production of erythrocytes. In severe cases, blood transfusions will be required and identification and treatment of the underlying problem (including valve replacement for cases requiring frequent blood transfusions).

Prosthetic valve endocarditis

Early prosthetic heart valve endocarditis (≤ 2 months after implantation) is usually caused by staphylococcus epidermidis and often presents as acute endocarditis with a fulminant clinical course and high mortality rates (>20%). Late prosthetic valve endocarditis is usually caused by microorganisms that are the usual pathogens in native valve endocarditis, such as streptococci which are the most common causative agents, followed by gram negative bacteria and enterococci.
The imaging modality of choice is transesophageal echocardiography (TEE) which can detect vegetations, or complications of prosthetic valve endocarditis, such as valve dehiscence or an abscess.

Paravalvular leak or paravalvular regurgitation of prosthetic heart valves

It is the regurgitation of blood in an area just next to the sewing ring of the valve, due to a poor contact of the valve with adjacent tissues to which it has been sutured. Possible causes include an infection (endocarditis), calcification or fibrosis of the native valve annulus, resulting in poor contact with the suture ring, or suture detachment. In patients with a mild (small) paravalvular leak, the prognosis is good and only periodic follow-up is required. In a severe paravalvular leak that causes symptoms, significant hemolysis, or left ventricular dilation due to volume overload, surgical or transcatheter management is required. A paravalvular leak is more common with transcatheter aortic valve implantation (TAVI) than with surgical implantation of a prosthetic valve.

Prosthetic valve dehiscence

Dehiscence (detachment) of the prosthetic valve suture ring from the valve annulus may occur in the early postoperative period due to surgical errors, the presence of extensive calcification of the valve annulus, infection (endocarditis), fragile valve annular tissue due to previous surgery, or chronic corticosteroid use. Late dehiscence of a prosthetic valve is due to infectious endocarditis. An indication of valve dehiscence is an abnormal rocking motion of the prosthetic valve in echocardiography or fluoroscopic examination. Dehiscence is an indication for emergency surgery.

Prosthetic heart valve structural degeneration

Bioprosthetic valves, as opposed to mechanical valves, have the advantage of being less thrombogenic, but they also have the disadvantage that they develop degenerative lesions over the years (thickening and/or calcification with progressive stenosis or regurgitation). Factors associated with increased risk for a patient to develop degenerative lesions in a bioprosthetic valve are young, age, a bioprosthetic valve in the mitral position, renal failure, and hyperparathyroidism. The most common cause of malfunction of a bioprosthetic valve is the structural degeneration of the valve causing valve stenosis or regurgitation.
Reoperation is required once symptoms develop (class I), or even in asymptomatic patients with severe regurgitation, or severe stenosis of the bioprosthesis because reoperation at a stable stage reduces the risk of this second operation and thus may be justified. The risk associated with reoperation in a stable patient is only slightly higher than the risk of the first operation. Bioprosthetic aortic valve failure in patients with a high surgical risk can be treated by transcatheter valve‐in‐valve implantation. 

LINK: Cardiology book- Table of contents


Zoghbi, WA, et al. Recommendations for Evaluation of Prosthetic Valves With Echocardiography and Doppler Ultrasound. Journal of the American Society of Echocardiography 2009;22: 075-1014.

Baumgartner H, et al. 2017 ESC/EACTS Guidelines for the management of valvular heart disease: The Task Force for the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS), European Heart Journal, ehx391,

Chambers JB. Prosthetic heart valves. The International Journal of Clinical Practice 2014; 68:1227-1230 LINK

Bajaj RKarthikeyan G, et al.CSI consensus statement on prosthetic valve follow up. Indian Heart Journal 2012; 64: S3 -S11 LINK

Habets, J. et al. Diagnostic evaluation of left-sided prosthetic heart valve dysfunction Nat. Rev. Cardiol 2011;8: 466-478.

Huang G1, Schaff HV, et al. Treatment of obstructive thrombosed prosthetic heart valve.J Am Coll Cardiol. 2013 ;62:1731-1736.