Heart failure: Pathology review

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Case Study0:00–0:50

On the cardiology ward, two patients had been admitted multiple times. The first is Lydia, a 70-year-old woman with a history of myocardial infarction about 3 years ago.
Now, she reports fatigue and shortness of breath. Lydia often wakes up at night gasping for air, but using extra pillows offers some relief.
On examination, she has pitting edema in her legs, and on auscultation, an S3 sound is heard. The second patient is an 81-year-old man, Richard, with a history of tobacco consumption for the past 50 years.
He also reports fatigue and has pitting edema. But in his case, the physical exam reveals jugular venous distention and hepatomegaly.
Both Lydia and Richard are dealing with heart failure. Heart failure is a clinical syndrome that describes the heart's inability to pump enough blood to meet the body's metabolic demands, or being able to do so only at abnormally high filling pressures.

Pathology0:50–1:31

Now, heart failure can happen in two main ways. If the heart can't pump out enough blood with each contraction, we call it heart failure with reduced ejection fraction, or HFF.
This used to be known as systolic heart failure. On the flip side, if the heart contracts normally but doesn't relax well enough to fill, as it normally should, it's called heart failure with preserved ejection fraction, or HFF.
This type was known as diastolic heart failure. In both cases, blood backs up into the circulation, causing congestion or fluid build-up.

Systolic Heart Failure1:31–3:43

That's why heart failure is often referred to as congestive heart failure, or CHF. Let's start with heart failure with reduced ejection fraction.
To understand what's going on here, it helps to start with the bigger picture, which is cardiac output. Cardiac output is the total amount of blood the heart pumps in one minute.
To calculate it, you simply multiply heart rate by stroke volume. Heart rate is how many times the heart BPM, and stroke volume is the amount of blood that the heart pumps out into the circulation with each beat.
But not all of the blood from the ventricles enters the circulation with each contraction. Suppose there are 110 mL of blood in the ventricle before contraction, which represents the end diastolic volume.
If the ventricle pumps 70 mL into the circulation, the stroke volume is 70 mL. The volume left in the ventricle after contraction is 40 mL and represents the end systolic volume.
This brings us back to ejection fraction. To calculate this, we divide stroke volume by the end diastolic volume multiplied by 100.
This is the percentage of total blood in the ventricles that's ejected with each contraction. In our case, the ejection fraction is 70 mL divided by 110 mL, which is approximately 64%.
This is considered normal, because the typical range varies from 50% to 70%. Now in heart failure with reduced ejection fraction, the heart muscle is weak, and can't contract effectively.
As a result, ejection fraction decreases, causing stroke volume to drop, subsequently reducing cardiac output. With less blood being pumped out, more blood remains in the ventricle after each beat.

Diastolic Heart Failure3:43–5:09

Over time, this increases the end diastolic volume, and as the volume rises, so does the end diastolic pressure. The most common causes of heart failure with reduced ejection fraction include conditions that reduce contractility, such as myocardial infarction, where a part of the cardiac tissue is damaged and won't contract properly.
Another cause is dilated cardiomyopathy, where the ventricle becomes enlarged and weakened. Now, let's switch gears and talk about heart failure with preserved ejection fraction.
In this case, the heart muscle is not weak, and the heart's ability to contract remains intact. The issue is that the heart is stiff or non-compliant, meaning it doesn't relax properly during diastole.
Early on, the end diastolic volume might still appear normal because the atria can compensate by squeezing more blood into the ventricle.
However, this compensation doesn't last forever. Over time, less blood enters the stiff ventricle, causing a decrease in end diastolic volume.
But since the ventricle walls don't stretch well, even this limited volume of blood creates higher than normal pressure, eventually increasing the end diastolic pressure.
In other words, the end diastolic volume is low, but the end diastolic pressure is high. With less blood filling the ventricle, stroke volume eventually drops.

Left Heart Failure5:09–9:37

However, the ejection fraction remains normal, because the percentage of blood pumped out relative to what was inside the ventricle is still within the normal range.
For example, suppose the stroke volume is 44 mL, and N diastolic volume is 69 mL. Dividing 44 by 69 gives an ejection fraction of about 64%, which falls within the normal range of 50 to 70%.
One common cause of heart failure with preserved ejection fraction is ventricular hypertrophy. Where the ventricular myocardium gets thicker.
This reduces the ventricular ability to stretch during diastole, making it harder to fill properly. Heart failure can occur with either reduced or preserved ejection fraction, and can affect the right, left, or both ventricles, a condition called biventricular heart failure.
The terms primarily describe the initial site of dysfunction. But, because the right and left ventricles work in series, dysfunction in one eventually impacts the other.
In left heart failure, less blood enters the aorta, so the blood backs up into the left atrium and pulmonary veins. As blood backs up, pressure in pulmonary capillaries rises, pushing fluid first into the interstitial space, and in more severe cases, into the alveoli.
This is called pulmonary edema. Pulmonary edema impairs oxygen and carbon dioxide exchange, causing shortness of breath, or dyspnea.
Another symptom is difficulty breathing when lying flat, or orthopnea. This is because there's more venous return from the legs and the gut to the heart, which increases the amount of blood backing up into the pulmonary circulation.
This also explains why these individuals experience paroxysmal nocturnal dyspnea, or the sensation of shortness of breath during the night.
Many will use extra pillows to keep their upper body elevated, reducing venous return and easing lung congestion. On auscultation, the extra fluid in the lungs causes crackles or rales.
If enough fluid fills the capillaries in the lungs, they can rupture, causing blood to leak into the alveoli. Alveolar macrophages then eat up these red blood cells, which causes them to take on this brownish color from iron build-up.
These cells are called hemosiderin-laden macrophages, or heart failure cells. In left heart failure, decreased cardiac output can cause non-specific symptoms, like fatigue and exercise intolerance.
With less blood reaching vital organs, the kidneys sense reduced perfusion, and respond by activating the renin angiotensin aldosterone system, or RASS for short.
This triggers sodium and water retention in renal tubules, which increases intravascular volume and venous return, effectively increasing preload, or the stretch of the ventricles before contraction.
In other words, the body increases end diastolic volume. At first, this helps, because based on the Frank Starling mechanism, More stretch means stronger contractility.
But RAS also induces vasoconstriction of small blood vessels, thereby increasing afterload, which is the resistance the left ventricle must overcome to eject blood into systemic circulation.
So, something that's supposed to help, ends up hurting the heart, by making it work even harder, and pushing it closer to failure.
Unfortunately, in the long-term, large portions of this extra fluid will end up leaking into the tissues, which worsens the pulmonary edema, and it will also lead to peripheral edema.
This is sometimes called pitting edema, because the tissue is visibly swollen, and when you apply pressure to it, it leaves a pit.
Apart from this, the low cardiac output triggers the sympathetic nervous system, which increases heart rate and contractility in an attempt to maintain perfusion.

Right Heart Failure9:37–11:31

At the same time, this raises the heart's oxygen demand and accelerates myocyte stress and damage. Over time, this chronic strain promotes ventricular remodeling, causing the heart to become larger, stiffer, and less efficient.
Finally, an important thing to remember is that in heart failure, you might hear an extra heart sound on auscultation. Normally, the heart makes two sounds.
S1 occurs when the mitral and tricuspid valves close, marking the start of systole, while S2 occurs when the aortic and pulmonary valves close, marking the start of diastole.
Together, these two create that classic sound, lubdub, lubdub. Now, in long-standing heart failure with reduced ejection fraction, which is associated with ventricular dilation, you might hear an S3 sound.
S3 occurs right after the S2 sounds, when the blood rushes into the dilated ventricle, creating a low pitch sound known as an S3 gallop, or ventricular gallop.
On the other hand, in heart failure with preserved ejection fraction, you might hear an S4 sound just before S1. S4 occurs when the atrium contracts forcefully to push blood into a stiff ventricle.
When the blood hits stiff ventricular walls, it produces an audible vibration, called S4 gallop, also known as atrial gallop.
Now, let's switch gears and talk about right-sided heart failure. Remember, the most common cause of heart failure is left heart failure.
When the left heart fails, blood backs up into the lungs, subsequently increasing pressure in the pulmonary artery. Now, the right ventricle must pump against higher pressure.

Treatment11:31–12:54

This extra strain initially causes right ventricular hypertrophy, which is a compensatory response. But, if the pulmonary pressure remains elevated, the right ventricle eventually decompensates and dilates.
That's when right-sided heart failure develops. Another important cause of right heart failure is lung conditions that impair oxygen exchange, like emphysema or pulmonary embolism.
Low oxygen levels cause small pulmonary arterials to constrict, raising pressure in the pulmonary artery. Again, this forces the right side of the heart to work harder to pump blood into the lungs.
Over time, this extra strain can lead to right ventricular hypertrophy, dilation, and eventually, right heart failure. In right-sided heart failure, blood gets backed up to the body, and so individuals will have congestion in the veins of the systemic circulation.
One common manifestation of this is jugular venous distention, where the jugular vein that's relatively close to the heart, becomes enlarged and distended.
Also, in the body, when blood backs up to the liver, it causes venous congestion there, and eventually, fluid can move into its interstitial spaces, causing the liver to become enlarged, which is called hepatomegaly.

Review12:54–14:22

There's a special name for this particular type of hepatopathy called congestive hepatopathy. On pathology, there's a so-called nutmeg liver, because you can see the congested hepatic venules and veins as dark spots, and it actually looks like a grated nutmeg.
If the liver is congested for long periods of time, patients can eventually develop cirrhosis and liver failure, which is called cardiac cirrhosis.
Finally, fluid that backs up into the interstitial space in the soft tissues of the legs causes pitting edema. In terms of treatment, let's start with heart failure with reduced ejection fraction.
An important point to remember here is that certain medications can reduce mortality in patients with this type of heart failure.
These include angiotensin converting enzyme, or ACE inhibitors, angiotensin receptor blockers, or ARBs, aldosterone receptor antagonists like spironolactone, And certain beta blockers, specifically carvedilol, bisoprolol, and metoprolol.
Keep in mind though, that beta-blockers must be used with caution in decompensated heart failure, because they decrease heart rate and have a negative inotropic effect, meaning they reduce the strength of the heart's contraction.

Summary14:22–18:12

Next, we have vasodilators, such as hydralazine, combined with nitrates, which can also reduce mortality. Finally, there are two additional types of mortality-decreasing medications for HEFREF.
Neprolysin inhibitors, like sacubitril, work by inhibiting neprolysin, an enzyme that breaks down the peptides that promote urine sodium excretion and vasodilation.
But, because neprolysin also breaks down vasoconstrictors like angiotensin 2, inhibiting it alone can increase levels of angiotensin 2, and raise BP, making heart failure worse.
To prevent this, and make the drug helpful in treating heart failure, neprolysin inhibitors are combined with angiotensin receptor blockers, which block the effects of angiotensin 2.
The other group includes sodium glucose co-transporter too. SGLT2 inhibitors, which cause the kidneys to excrete more glucose and sodium, pulling water along with them, and therefore producing a diuretic effect.
This reduction in fluid leads to less work for the heart. SGLT2 inhibitors also appear to improve cardiac energy metabolism and reduce inflammation, among other mechanisms that help with heart failure.
Now, the key here is that while other medications help reduce mortality only in Hef-REF, SGLT2s on the other hand, help reduce mortality in Hef-PF as well.
Beyond that, treatment of Hef-PF mainly focuses on symptom relief through diuresis. Loop and thiazide diuretics are used in both types of heart failure to relieve symptoms by reducing the overall fluid build-up in the body, but they do not influence mortality.
Alright, as a quick recap. Heart failure is a clinical syndrome where the heart is unable to pump enough blood to meet the body's metabolic demands, or it can only do so at abnormally high filling pressure.
Now heart failure can happen in two main ways. If the heart can't pump out enough blood with each contraction, we call it heart failure with reduced ejection fraction.
On the flip side, if the heart contracts normally, but doesn't relax well enough to fill as it normally should, it's called heart failure with preserved ejection fraction.
Heart failure can affect the right ventricle, the left ventricle, or both. The most important clinical features include dyspnea, orthopnea, rails, fatigue, jugular venous distention, and pitting edema.
On auscultation, common findings include an S3 or occasionally an S4. Now, back to our cases, 70 year old Lydia came in with a history of myocardial infarction.
She's now experiencing fatigue and shortness of breath. While the exam reveals pitting edema and an S3 sound, her echocardiogram showed a low ejection fraction, indicating heart failure with reduced ejection fraction.
Her other symptoms like dyspnea, paroxysmal nocturnal dyspnea, and orthopnia, point towards left-sided heart failure. On the other hand, 81 year old Richard presents with fatigue, pitting edema, jugular venous distention, and hepatomegaly.
His echocardiogram shows a normal ejection fraction, but right ventricular hypertrophy. These findings, along with his symptoms, suggest right-sided heart failure from a pulmonary cause.
Since he has a 50-year history of smoking, emphysema is a likely cause. Next step is to get a chest X-ray and spirometry.