Leukemia (Blood Cancer)

Congestive Heart Failure 

Heart failure’s used to describe a point at which the heart can’t supply enough blood to meet the body’s demands. This can happen in two ways, either the heart’s ventricles can’t pump blood hard enough during systole, called systolic heart failure, or not enough blood fills the ventricles during diastole, called diastolic heart failure.

In both cases, blood backs up into the lungs, causing congestion or fluid buildup, which is why it’s also often known as congestive heart failure, or just CHF. Congestive heart failure affects millions of people around the world and since it means that the body’s needs are not being met, it can ultimately lead to death. Part of the reason why so many people are affected by heart failure is that there are a wide variety of heart diseases like ischemia and valvular disease that can impair the heart’s ability to pump out blood and—over time—can ultimately cause the heart to fail.

Alright, first up is systolic heart failure, kind of a mathematical way to think of this one is that the heart needs to squeeze out a certain volume of blood each minute, called cardiac output, which can be rephrased as the heart rate (or the number of beats in a minute) multiplied by the stroke volume (the volume of blood squeezed out with each heartbeat). The heart rate is pretty intuitive, but the stroke volume’s a little tricky. For example, in an adult, the heart might beat 70 times per minute and the left ventricle might squeeze out 70ml per beat, so 70 x 70 equals a cardiac output of 4900ml per minute, which is almost 5 liters per minute. So notice that not all the blood was pumped outright? And the stroke volume is a fraction of the total volume. The total volume may be closer to 110 ml, and 70ml is the fraction that got ejected out with each beat, the other 40ml kind of lingers in the left ventricle until the next beat, right?

In this example, the ejection fraction would be 70ml divided by 110ml or about 64%, a normal ejection fraction is around 50-70%, between 40-50% would be borderline, and anything about 40% or less would indicate systolic heart failure because the heart is only squeezing out a little blood each beat. So in our example, if the total volume of the left ventricle was 110ml, but only 44ml was pumped out with each beat (then you have 44ml divided by 110 ml which is 40%), we would say that this person is in systolic heart failure. Now in addition to systolic heart failure, you’ve also got diastolic heart failure, which is where the heart squeezing hard enough but not filling quite enough. In this case, again the stroke volume is low, but the ejection fraction’s normal...how’s that?

Well, it’s not filling enough so there’s a low total volume, which says about 69ml, and well even though both are low, 44ml divided by 69ml is still 64%. In this situation, the failure’s caused by the abnormal filling of the ventricle so that the chamber doesn’t get fully loaded or stretched out in the first place. Another term for this is having a reduced “preload” which is the volume of blood that’s in the ventricle right before the ventricular muscle contracts. An important relationship between systolic and diastolic function is the Frank-Starling mechanism, which basically shows that loading up the ventricle with blood during diastole and stretching out the cardiac muscle makes it contract with more force, which increases stroke volume during systole.

This is kind of like how stretching out a rubber band makes it snap back even harder, except that cardiac muscle is actively contracting whereas the rubber band is passively going back to its relaxed state. Heart failure can affect the right ventricle, the left ventricle, or both ventricles, so someone might have, right-sided heart failure, left-sided heart failure, or both (which is called biventricular heart failure), each of which can have systolic or diastolic failure. Having said that, if less blood exits either ventricle it’ll affect the other since they work in series, so left-sided could cause right-sided, and vice versa, so these terms really refer to the primary problem affecting the heart, basically which one was first.

Usually, left-sided heart failure is caused by systolic (or pumping) dysfunction. This is typically due to some kind of damage to the myocardium—or the heart muscle—which means it can’t contract as forcefully and pump blood as efficiently. Ischemic heart disease caused by coronary artery atherosclerosis, or plaque buildup, is the most common cause. In this case, less blood and oxygen gets through the coronary artery to the heart tissue, which damages the myocardium? Sometimes, if the coronary’s blocked completely and the person has a heart attack, they might be left with scar tissue that doesn’t contract at all, which again means the heart can’t contract as forcefully. Longstanding hypertension is another common cause of heart failure. This is because as arterial pressure increases in the systemic circulation, it gets harder for the left ventricle to pump blood out into that hypertensive systemic circulation.

To compensate, the left ventricle actually bulks up, and its muscles hypertrophy or grow so that the ventricle can contract with more force. The increase in muscle mass also means that there is a greater demand for oxygen, and, to make things even worse, the coronaries get squeezed down by this extra muscle so that even less blood’s delivered to the tissue. More demand and reduced supply mean that some of the ventricular muscle starts have weaker contractions—leading to systolic failure. Another potential cause would be dilated cardio-myopathy, where the heart chamber dilates or grows in size in an attempt to fill up the ventricle with larger and larger volumes of blood, or preload, and stretch out the muscle walls and increase contraction strength, via the Frank-Starling mechanism.

Even though this can work for a little while, over time, the muscle walls get thinner and weaker, eventually leading to muscles that are so thinned out that it causes systolic left-sided heart failure. Ultimately the ventricle walls need to be the right size relative to the size of the chamber in order for the heart to work effectively. Any major deviation from that can lead to heart failure. Even though systolic failure is most common in left-sided heart failure, diastolic heart failure or filling dysfunction can also happen. In hypertension, remember how the left ventricular hypertrophied? Well, that hypertrophy is concentric, which means that the new sarcomeres are generated in parallel with existing ones.

This means that as the heart muscle wall enlarges, it crowds into the ventricular chamber space, resulting in less room for blood, meaning that in addition to contributing to systolic dysfunction, hypertension also can cause diastolic heart failure. Concentric hypertrophy leading to diastolic failure can also be caused by aortic stenosis, which is a narrowing of the aortic valve opening, as well as hypertrophic cardiomyopathy, an abnormal ventricular wall thickening often from a genetic cause. Restrictive cardio-myopathies are yet another cause. In this case, the heart muscle gets stiffer and less compliant, and therefore the left ventricle can’t easily stretch out and fill with as much blood, which leads to diastolic heart failure.

When the heart doesn’t pump out as much blood, there’s decreased blood flow to the kidneys, which activates the renin-angiotensin-aldosterone system, ultimately causing fluid retention. Which fills the heart a bit more during diastole and increases preload, which increases contraction strength again by the Frank-Starling mechanism? Unfortunately, just like the other strategies, in the long term, retaining fluid so that more fluid remains in the blood vessels typically leads to a large portion of it leaking into the tissues and can contribute to fluid buildup in the lungs and other parts of the body, which can worsen the symptoms of heart failure.

Alright, so a major, major clinical sign of the heart not being able to pump enough blood forward to the body is that blood starts to back up into the lungs. A backup of blood in the pulmonary veins and capillary beds can increase the pressure in the pulmonary artery and can also result in fluid moving from the blood vessels to the interstitial space causing pulmonary edema, or congestion. In the alveoli of the lungs, all this extra fluid makes oxygen and carbon dioxide exchange a lot harder, since a wider layer of fluid takes more time for oxygen and carbon dioxide to diffuse through, and therefore patients have dyspnea—trouble breathing, as well as orthopnea - which is difficulty breathing when lying down flat since that allows venous blood to more easily flow back from the legs and the gut to the heart and eventually into the pulmonary circulation.

This extra fluid in the lungs causes crackles or rales to be heard during auscultation while the patient breathes. If enough fluid fills some of these capillaries in the lungs, they can rupture, leaking blood 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. And then they’re then called “hemosiderin-laden macrophages”, also known as “heart failure cells”. For left-sided heart failure, certain medications can be prescribed to help improve blood flow, like ACE inhibitors which help dilate blood vessels, as well as diuretics to help reduce the overall fluid buildup in the body which helps prevent hypertension from worsening the heart failure.

Now let’s switch gears and think about right-sided heart failure, which is actually often caused by left-sided heart failure. K remember how fluid buildup increased pressure in the pulmonary artery? Well, this increased pulmonary blood pressure makes it harder for the right side to pump blood into. In this case, the heart failure would be biventricular since both ventricles are affected. Someone can also have isolated right-sided heart failure, though, and an example of this would be a left-to-right cardiac shunt. In these cases, there might be a cardiac shunt like an atrial septal defect or a ventricular septal defect, that allows blood to flow from the higher-pressure left side to the lower-pressure right side, which increases the fluid volume on the right side and can eventually lead to concentric hypertrophy of the right ventricle, making it more prone to ischemia—which is a systolic dysfunction, and have a smaller volume and become less compliant—which is diastolic dysfunction.

Another potential cause of isolated right-sided failure is a chronic lung disease. Lung diseases often make it harder to exchange oxygen. Well in response to low oxygen levels or hypoxia, the pulmonary arterioles constrict, which raises the pulmonary blood pressure. This, just like before, makes it harder for the right side of the heart to pump against and can lead to right-sided hypertrophy and heart failure. When chronic lung disease leads to right-sided hypertrophy and failure, it’s known as cor-pulmonale. With left-sided failure, blood gets backed up into the lungs. With right-sided failure, blood gets backed up to the body, and so patients have congestion in the veins of the systemic circulation. One common manifestation of this is jugular venous distention, where the jugular vein that brings blood back to the heart takes on more blood and becomes enlarged and distended in the neck.

Also in the body, when blood backs up to the liver and spleen, fluid can move into the interstitial spaces within those organs and they can both become enlarged, called hepatosplenomegaly, which can be painful, and if the liver is congested for long periods of time, patients can eventually develop cirrhosis and liver failure, which would be called cardiac cirrhosis. Excess interstitial fluid near the surface of the liver and spleen can also move right out into the peritoneal space as well, and since that cavity can take a lot of fluid before there is an increase in pressure, a lot of fluid can build up in the peritoneal space which is called ascites.

Finally, fluid that backs up into the interstitial space in the soft tissues in the legs causes pitting edema, where the tissue is visibly swollen and when you apply pressure to it leaves a “pit” and takes a while to come back to its original place. This generally affects the legs in most people, because gravity generally causes the majority of fluid to “pool” in the dependent parts of the body, which are the legs when you’re standing and the sacrum, essentially the lower back, when you’re lying down. Right-sided heart failure will be treated similarly to left-sided heart failure, especially because it’s often a result of left-sided heart failure. Therefore, medications like ACE inhibitors and diuretics may be prescribed. With heart failure, we saw that sometimes the muscle wall can stretch and thin out, or sometimes it can sometimes thicken and become ischemic.

In either case, those heart cells get irritated, in both scenarios the cells get irritated, and this can lead to heart arrhythmias. With an arrhythmia, the ventricles don’t contract in sync anymore making them less able to pump out blood and worsening the whole situation. In some cases, patients might be treated with cardiac resynchronization therapy pacemakers, which can stimulate the ventricles to contract at the same time and potentially improve the blood pumped out. Alternatively, for heart failure in general, some people might have ventricular assist devices implanted, or VADs, which literally assist or help the heart pump blood may also be implanted. In end-stage situations where other forms of treatment have failed, patients might have a heart transplant.