Valvular heart disease: Pathology review

Definitions & Key takeaways

Valvular heart disease refers to a group of conditions that affect the heart's valves. The valves within the heart include the mitral, aortic, tricuspid, and pulmonary valves. Some examples of valvular heart disease include aortic stenosis, which is the narrowing of the aortic valve; aortic regurgitation in which blood leaks back through the aortic valve; mitral regurgitation in which there is a narrowing of the mitral valve; mitral stenosis characterized by blood leaking back through the mitral valve tricuspid regurgitation in which blood leaks back through the tricuspid valve; pulmonary stenosis that's characterized by the narrowing of the pulmonary valve; and finally; pulmonary regurgitation in which blood leaks back through the pulmonary valve.

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Case Study0:00–0:44

On the Cardiology ward, there are two individuals. One of them is 75 year old Antonia, who’s complaining of chest pain and says she hardly catches her breath after walking.
On clinical examination, her pulse feels pretty weak and on auscultation, a systolic murmur is heard. The murmur was louder just after S1 and got quieter and quieter by the end of S2.The other individual is 38 year old Mark who has a history of rheumatic fever and is complaining of not being able to swallow properly.
On clinical examination, his voice sounds raspy and on auscultation, a snap is heard after S2 along with a diastolic rumble.
Based on auscultation, both individuals were sent for echocardiography.Okay, so based on auscultation and symptoms, both individuals seem to have valvular heart disease.

Pathology0:44–1:04

Valvular heart disease involves damage or a defect in one or more of the four valves of the heart, so the aortic and mitral valves on the left side of the heart, and the pulmonary and tricuspid valves on the right side of the heart.
Okay, now, before talking specifics about valvular disease, we’ll first talk about rheumatic fever, which can affect multiple valves.

Rheumatic Fever 1:04–5:00

Rheumatic fever can develop after streptococcal infection like strep throat, which is caused by Streptococcus pyogenes. This particular group of streptococcus has an antigen that lumps it into a group called “group A”, and they also produce an enzyme called streptolysin, which causes hemolysis.
Some of these strep bacteria have a protein on their cell wall called “M protein”, and this particular protein is highly antigenic, meaning that the immune system sees it and recognizes it as a foreign molecule and produces antibodies against it.
Now, this becomes a problem when these antigens cause a phenomenon called molecular mimicry. M proteins can be structurally similar to human proteins, which means the antibodies that target them will also target our own tissue.
In this case, they are similar to proteins found in the myocardium and heart valves. Once bound to cardiac tissue, the antibodies activate nearby immune cells, which causes a cytokine-mediated inflammatory response and tissue destruction.
This is also an example of what’s called a type 2 hypersensitivity reaction. All right, so not everyone that gets strep throat gets rheumatic fever, and it’s actually only a small minority that get it.
However, the individuals that do get rheumatic fever from strep infections will have a variety of clinical findings. These make up the Jones criteria which is divided into 5 major criteria that you have to remember, and 5 minor criteria that are also good to keep in mind.
Let’s go over the major criteria first.The most common is migratory polyarthritis of the joints, where multiple large joints become inflamed, swollen and painful, then the inflammation resolves and spreads to other joints.
Secondly, some patients have carditis. The inflammation can affect the endo, myo, and pericardium.
Since the endocardium includes the valves, they too are affected. A high yield fact to remember is that the mitral valve is most commonly affected, although the aortic and tricuspid valve can also be affected.
In the acute phase of the illness, mitral regurgitation is most common. Later on, fibrosis around the valve causes its leaflets to fuse together, giving it a fish-mouth-like appearance.
This fusion narrows the valve opening, and so we get mitral stenosis.Now, although not a part of the Jones criteria, a high yield fact is that in histology, there will be Aschoff bodies in the heart.
These are granulomas with giant cells consisting of areas of fibrinoid necrosis and lymphocytic infiltration. Within Aschoff bodies, there are characteristic Anitschkow cells which are enlarged macrophages that have a characteristic caterpillar-looking nucleus.
Now for the rest of the Jones criteria, the hypersensitivity reaction in rheumatic fever can affect the skin. So the next criteria is subcutaneous nodules, which are these firm lumps under the skin made up of collagen.
The fourth is erythema marginatum, a reddish rash that shows up as rings on the arms or trunk. And finally, there’s Sydenham’s chorea, which is a set of rapid movements of the face and the arms, caused by an autoimmune reaction against the basal ganglia of the brain.For the minor criteria, there’s polyarthralgia, fever greater or equal to 38.5 degrees celsius, blood tests showing an ESR greater or equal to 60 mm/h, or a CRP greater or equal to 3 mg/dl, prolonged P-R interval, and a blood test that shows evidence of previous streptococcal infection, such as high titers of anti-streptolysin-O, or ASO.
Treatment and prophylaxis of rheumatic fever is done using penicillin.Okay, now let’s look at the specific valvular heart diseases.

Murmurs 5:00–6:01

They can be divided into stenosis, where there’s narrowing of the valvular orifice that prevents adequate outflow of blood, and insufficiency or regurgitation, where the valvular leaflets fail to close correctly and are unable to prevent backflow of blood.
In order to make things easier to remember, we’ll classify valvular disease based on what type of murmurs you hear on auscultation.
Remember there are two normal heart sounds; S1, caused by the mitral and tricuspid valves closing at the beginning of systole, and S2, caused by the aortic and pulmonary valves closing at the beginning of diastole.So first, there are systolic murmurs, which you can hear right after S1 and these happen with aortic stenosis, mitral and tricuspid valve regurgitation.
Then there are diastolic murmurs, which come right after S2 and these happen with aortic regurgitation and mitral stenosis.Let’s start with systolic murmurs and look at aortic stenosis.

Aortic Stenosis 6:01–9:26

The aortic valve is typically made up of three leaflets: the right, left, and posterior leaflet and it opens during systole to allow blood to be ejected to the body.
During diastole, it closes to allow the heart to fill with blood and get ready for the next systole. Aortic stenosis is when the aortic valve doesn’t open all the way and it gets harder to pump blood into the aorta.Aortic stenosis is usually caused by chronic mechanical stress that damages endothelial cells around the valves, causing fibrosis and calcification, which hardens the valve and makes it more difficult to open completely.
This type usually shows up in late adulthood, so for your exams, remember that this is more common in individuals over 60 years old.
Now, if there’s aortic stenosis in a younger individual, the cause could be due to a bicuspid valve. These abnormal valves are more at risk of fibrosis and calcification since the mechanical stress is now being split by just two leaflets.Okay, let’s go over auscultation now.
With aortic stenosis, since blood has to flow through a narrow aortic valve, there’s turbulence which creates noise, or a murmur.
This initially gets louder as more blood flows past the opening and then quieter as the amount of blood flowing subsides.
This is called a crescendo-decrescendo murmur and you can hear this right after S1. This sound is best heard in the aortic area and typically radiates in the carotids.
The intensity of the murmur increases as the pressure gradient between the left ventricle and the aorta increases. So, the narrower the stenosis, the louder the murmur.
Now, normally, S2 has two components: the aortic component and the pulmonary component since the valves don’t close at the same time.
Typically, the aortic valve closes first and then the pulmonary valve. But with aortic stenosis, the aortic valve closes later than expected and so it may close at the same time with the pulmonary valve, in which case you’ll hear a soft S2.
Another important clue that will likely show up on your exam is the ejection click, since the valve fuses together or hardens, it doesn’t open as easily.
And so as the left ventricle contracts, it creates this high pressure that eventually pushes on the valve until it finally snaps open, causing a clicking sound.
In aortic stenosis, the pulse is described as being “parvus and tardus”. That’s because the valve doesn’t fully open so there’s less blood flow and the pulse is weak, or “parvus”, and there’s a delay in the opening of the valve that occurs a bit later than expected, so, the pulse is also late, or “tardus”.
Even though the ventricle tries to pump out more blood, the heart still might struggle to get enough blood through the narrowed opening and then to the rest of the body.For example, if there’s a reduction in blood flow to the brain, it could lead to syncope, and a reduction in blood flow through the coronary arteries to the heart’s own myocardium could cause chest pain and angina.
Individuals might not initially experience symptoms at rest, and problems only occur during exercise or exertion because there’s an increase in the demand for oxygen.
So, during exercise, they can also experience dyspnea. The next systolic murmur is caused by mitral regurgitation.

Mitral Regurgitation9:26–12:41

The mitral valve has two leaflets, the anterior and posterior leaflet, and together they separate the left atrium from the left ventricle.
During systole, the valve closes, which means blood has just one option, to be ejected out through the aortic valve and into circulation.
Mitral regurgitation is when the mitral valve doesn’t shut all the way, therefore blood can leak back into the left atrium.
The leading cause of mitral valve regurgitation in the United States, and the most common of all valvular conditions, is mitral valve prolapse.
Normally, when the left ventricle contracts during systole, a ton of pressure is generated to pump blood out through the aortic valve.
This also means a lot of pressure pushes on that closed mitral valve. Normally, the papillary muscles and connective tissue called chordae tendineae keep the valve from prolapsing or falling back into the atrium.However, sometimes there’s myxomatous degeneration where connective tissue of the leaflets and surrounding tissue are weakened.
Why this happens isn’t well understood, but it is sometimes associated with connective tissue disorders like Marfan syndrome and Ehlers-Danlos syndrome.
Mitral valve prolapse can also be caused by rheumatic fever or by chordae rupture during trauma. Regarding auscultation, mitral valve prolapse often has a classic heart murmur that you have to know for your tests.
This includes a mid-systolic click, meaning it appears between S1 and S2. This click is a result of the leaflet folding into the atrium and being suddenly stopped by the chordae tendineae.
If there’s mitral regurgitation, the mid-systolic click is sometimes followed by a crescendo systolic murmur that’s loudest just before S2 and is best heard over the apex.
Mitral valve prolapse is often asymptomatic, but it can predispose individuals to infective endocarditis.In addition to mitral valve prolapse, other causes of mitral regurgitation include damage to the papillary muscles from a myocardial infarction.
If these papillary muscles die, they can’t anchor the chordae tendineae, which then allows the mitral valve to flop back and allow blood to go from the left ventricle to the left atrium.
Also, left-sided heart failure that leads to ventricular dilation can lead to mitral regurgitation as well, because as the left ventricle dilates, it stretches the mitral valve annulus, or ring, wider and let's blood leak into the left atrium.
Mitral regurgitation can also be caused by rheumatic fever or by infective endocarditis without mitral prolapse. Here, chronic inflammation can cause leaflet fibrosis, which makes it so that they don’t form a nice seal and instead let blood leak through.
Now, the typical auscultation of mitral regurgitation is a holosystolic murmur, meaning it lasts for the duration of systole, so it’s heard between S1 and S2.
You may hear this, because with mitral regurgitation, blood is flowing back into the left atrium during systole. The sound is a high-pitched, blowing murmur that is loudest at the apex and radiates towards the axilla.Finally, there’s tricuspid regurgitation.

Tricuspid Regurgitation 12:41–13:42

The tricuspid valve has three leaflets: the anterior, posterior and medial or septal leaflets, and together they separate the right atrium from the right ventricle.
During systole, the tricuspid valve closes, and during diastole, the tricuspid valve opens and blood fills the right ventricle.
Tricuspid regurgitation happens when the tricuspid valve doesn’t close completely and blood leaks back from the right ventricle into the right atrium during systole.
Tricuspid regurgitation is most commonly caused by right ventricle dilatation, which in turn can be caused by pulmonary hypertension.
Other causes include rheumatic fever. The typical auscultation of tricuspid regurgitation is also a holosystolic, high-pitched blowing murmur like with mitral regurgitation, but this time is best heard in the tricuspid area.
You may hear this, because with tricuspid regurgitation, blood flows back into the right atrium during systole.Let’s now move on and talk about diastolic murmurs, specifically aortic regurgitation.

Aortic Regurgitation 13:42–15:57

Normally, right after the ventricle pumps blood out through the aortic valve, the valve shuts and remains shut until the ventricle fills again.
With aortic regurgitation, blood flows back from the aorta into the left ventricle during diastole. About half of the cases are caused by aortic root dilation where the leaflets are also pulled apart, making it harder for the valves to fit together and close all the way so some blood ends up flowing backwards.
Besides aortic root dilation, regurgitation can also happen due to valvular damage from something like rheumatic fever, infective endocarditis, or from a bicuspid aortic valve which doesn’t close properly.The typical auscultation in aortic regurgitation is a high-pitched early decrescendo diastolic murmur, which you can hear right after S2.
It’s caused by the blood flowing back through the valve. Now, since blood is leaking back from the aorta into the left ventricle, the left ventricular end diastolic volume increases.
Because there is a volume overload, the left ventricle responds by undergoing eccentric hypertrophy, which increases the stroke volume, or the amount of blood that the left ventricle pumps out during systole.
More blood pumped out of the heart per squeeze requires more pressure, so systolic blood pressure increases. However, during diastole, there’s less blood volume in the aorta since some has leaked back into the ventricle, which means that diastolic blood pressure decreases.A higher systolic pressure and lower diastolic pressure means an increase in pulse pressure, which is just systolic pressure minus diastolic pressure.
A large pulse pressure is referred to as a hyperdynamic circulation. People with hyperdynamic circulation have bounding pulses, or water-hammer pulses because the blood slams like a hammer against the walls of the arteries with each heartbeat.
In chronic and severe cases, these bounding pulses can be dramatic enough that they cause head bobbing that’s in tune with the heartbeat.
Over time, aortic regurgitation can progress to left heart failure.Finally, there’s mitral stenosis, which happens when the mitral valve doesn’t open enough.

Mitral Stenosis 15:57–18:01

This is highly specific and most often caused by rheumatic fever. In this case, the leaflets can fuse together, which is called commissural fusion.
The narrow mitral valve makes it a lot harder for blood to flow from the left atrium to the left ventricle and so the volume of blood in the left atrium increases, leading to higher pressures in the left atrium.
The pressure in the left atrium can be higher than that of the left ventricle.On auscultation, the pressure against the fibrotic mitral valve makes a “snap” sound when it opens, which you can hear milliseconds after S2.
A high yield concept is that the most reliable indicator of the severity of mitral stenosis is the interval between S2 and the opening snap.
The shorter the interval, the more severe the stenosis because when the pressure in the left atrium gets higher, the snap will happen earlier.
Finally, this opening snap sound is followed by a diastolic rumble as blood is forced through the smaller opening. This rumble intensifies just before systole because that’s when the left atrium contracts against the stenosed mitral valve.
In mitral stenosis, the left atrial pressure is increased and we can measure this by inserting a catheter through the right side of the heart, up the pulmonary artery and towards the end of it.
The catheter then reaches a point at which it cannot cross further. The pressure at this point is called the pulmonary capillary wedge pressure, or PCWP, because the catheter is “wedged” there.
The PCWP closely reflects the left atrial pressure, so in mitral stenosis, the PCWP is increased. Over time, a constant elevation in both blood volume and pressure in the left atrium causes it to dilate.
As a consequence, it can compress the esophagus, and patients might have difficulty swallowing solid foods, which is called dysphagia.
The dilated left atrium can also compress the left recurrent laryngeal nerve, leading to hoarseness of the voice.All right, as a quick recap… Rheumatic fever is caused by group A beta hemolytic streptococcus.

Review18:01–20:27

After the initial strep throat infection, some individuals will develop rheumatic fever. The Jones criteria for diagnosing rheumatic fever includes migratory polyarthritis, subcutaneous nodules, erythema marginatum, Sydenham’s chorea and last, but not least, carditis.
Specifically, rheumatic fever mostly affects the mitral valve, causing stenosis, but can also affect the aortic and tricuspid valves.
For the diagnosis, high titers of ASO are also needed.Now, valvular disease can be classified according to the type of murmurs heard on auscultation: systolic and diastolic murmurs.
Aortic stenosis, mitral and tricuspid regurgitation cause systolic murmurs, while aortic regurgitation and mitral stenosis cause diastolic murmurs.
Aortic stenosis happens when the endothelial cells around the valves undergo fibrosis and calcification. Aortic stenosis has a specific crescendo-decrescendo murmur heard just after S1 and sometimes, an ejection click can be heard.Next, there’s mitral regurgitation which is mostly caused by mitral valve prolapse, which is when the connective tissue of the leaflets and surrounding tissue are weakened.
On auscultation, mitral valve prolapse often has a mid-systolic click, followed by a crescendo systolic murmur. Mitral regurgitation can also be caused by damage after a myocardial infarction, ventricular dilation, rheumatic fever or infective endocarditis.
On auscultation, mitral regurgitation has a holosystolic murmur best heard over the apex. Now, tricuspid regurgitation is mostly caused by right ventricle dilation and also causes a holosystolic murmur, but this time it’s best heard over the tricuspid area.
For diastolic murmurs, there’s aortic regurgitation, which is mostly caused by aortic root dilation, but can also be caused by infective endocarditis, bicuspid aortic valve or rheumatic fever.
On auscultation, there’s a high-pitched early decrescendo diastolic murmur. There’s also an increase in pulse pressure, as well as hyperdynamic circulation.
Finally, there’s mitral stenosis, where on auscultation, there’s a snap sound after S2, as well as a diastolic rumble as blood is forced through the smaller opening.Okay, back to our cases!

Summary20:27–21:45

Antonia came in with angina and dyspnea and on the clinical examination, her pulse was weak and on auscultation, there was a systolic murmur that was louder after S1 and got quieter and quieter by the end of S2.
This systolic murmur that was heard sounds like a crescendo-decrescendo murmur that’s seen in aortic stenosis.Now, based on the symptoms, angina and dyspnea, her age and the clinical examination, weak pulses and systolic crescendo-decrescendo murmur, we can assume that Antonia suffers from aortic stenosis that’s caused by calcification and fibrosis around the aortic valve.
Echocardiography showed stenosis of the aortic valve.Now, Mark has a history of rheumatic fever and is complaining of dysphagia.
On the clinical examination, his voice was hoarse and on auscultation, a snap is heard after S2 with a diastolic rumble after the snap.
Based on his history of rheumatic fever, his symptoms of dysphagia and hoarseness, and auscultation, we can assume that Mark suffers from mitral stenosis and his left atrium might be really dilated, compressing the esophagus and the left recurrent laryngeal nerve.
Echocardiography confirmed mitral stenosis and a dilated left atrium and