What does a donkey have in common with the pathophysiology and treatment of congestive heart failure? More than you might imagine actually. Here is how I like to explain how the medical treatment of systolic congestive heart failure works to my students. You can review all of congestive heart failure here.
The heart is simply a muscle and a pump. When it is weak for any reason (see causes of congestive heart failure) it just can't keep up with the demands of the body. It gives out just like any muscle does it you over use it. When the heart is not pumping enough, the pressures inside the heart increase, fluid backs up in the system, and symptoms of congestive heart failure occur including shortness of breath and edema.
The body has two natural hormonal reactions to a low cardiac output: Increasing the activity of the sympathetic nervous system (epinephrine/norepinephrine) and increasing the renin-angiotensin aldosterone system of the kidney/adrenals.
The epinephrine increases afterload by stimulating alpha receptors, increases the contractility (squeezing force of the heart or inotropy) and heart rate by stimulating beta receptors. Increased renin and aldosterone result in sodium and fluid reabsorbtion increasing preload. Increased angiotensin vasoconstricts also increasing afterload (remember "angio" means vessel and "tensin" means to tense).
This puts a lot of stress on the heart. The heart is like a poor donkey pulling a heavy load of sandbags. The high preload and afterload are represented by the sandbags:
The problem is that a diseased heart (such as after a myocardial infarction) does not like this increased stress of the sympathetic nervous system activation and the increased RAAS, so the heart eventually further weakens. Think of this poor donkey having to pull this heavy wagon full of sandbags for 10 miles. Eventually it will collapse with exhaustion. Another analogy would be taking a 10 pound weight in your arm and pump it up and down. Eventually your arm muscle gets weak and you have no choice but to stop. Well, the heart is just a muscle and eventually if it is working too hard and simply can't keep up, it will weaken and the cardiac output will go down.
The preload (force in the venous system driving blood into the right heart) is high in congestive heart failure due to all the fluid being retained which mostly accumulates in the veins. Eventually this fluid gets forced into the tissues under the skin resulting in edema. The edema happens in the legs most commonly simply because gravity pulls it down (most people's legs are near the ground most of the day). Ascites (fluid in the abdomen) and pleural effusions can also occur.
To make the poor donkey feel better, we have to remove some of those sandbags!
In decompensated congestive heart failure, we do this by giving diuretics such as furosemide (Lasix) to force the kidneys to make more urine and eliminate the extra fluid which lowers the preload (sandbags). We have the patient restrict fluid intake to about 2 liters daily and keep a low sodium diet.
Also ACE inhibitors (i.e. lisinopril) and angiotensin receptor blockers (i.e. losartan) work to block the renin-angiotensin-aldosterone system (RAAS) also lowering preload (blocking aldosterone) and lowering afterload (angiotensin). Spironolactone works in heart failure by inhibiting aldosterone.
Lastly, hydralazine (a direct arterial vasodilator) decreases afterload and nitrates (i.e. isosorbide mononitrate) venodilate decreasing preload. The combination of hydralazine and nitrates are used in systolic congestive heart failure when ACE inhibitors and ARBs are contraindicated (i.e. kidney disease or hyperkalemia).
Here is the donkey after some good diureses, and afterload/preload reduction. It is simply like taking a load off the wagon making the work of the donkey much easier:
How about that increased sympathetic nervous system activity?
We use beta-blockers (i.e. metoprolol succinate or carvedilol) to ease the attack of the sympathetic nervous system on the heart. I remember as a student asking "If beta-blockers decrease heart rate and contractility, then don't they also decrease cardiac output? Wouldn't that make congestive heart failure worse since this is just a state of low cardiac output?". Recall that cardiac output is calculated by heart rate multiplied by stroke volume...so whats up?
Well, when a beta-blocker is FIRST started in systolic congestive heart failure, it can indeed lessen the cardiac output in the short term. That is why it is nice to be sure the patient is clinically stable before you give it (somewhat diuresed and certainly no pulmonary edema). EVENTUALLY, as the strain of the sympathetic nervous system is taken away from the poor sick heart muscle by the beta-blockers, it actually ends up increasing the cardiac output in the long term as the heart heals and the ejection fraction improves.
Beta-blockers are like saying to the donkey "Slow down a bit and rest. Don't work so hard! Regain your strength!" Anyone can go further if they take their time...slow and steady wins the race!
How about if we give the donkey some incentive to work harder?
There are two types of drugs used in congestive heart failure that can do this by directly increasing the cardiac output: Digoxin and sympathomimetics (i.e. dobutamine and milrinone).
Digoxin is unique and is reviewed here. Digoxin blocks the Na/K ATPase pump eventually resulting in increased intracellular calcium and increased contractility. Through unknown mechanisms (perhaps heightened tone of the parasympathetic nervous system), digoxin actually decreases heart rate. Digoxin ends up increasing the overall cardiac output and relieving the symptoms of congestive heart failure, but has never been shown to reduce mortality and certainly has some risk of toxicity.
Dobutamine and milrinone are given intravenously and act to stimulate the sympathetic nervous system including beta receptors. This increases heart rate and contractility resulting in an increased cardiac output improving symptoms of congestive heart failure.
Wait a second!!! Didn't we say that sympathetic nervous system stimulation is bad in a pathologically diseased heart and makes things worse? Yes indeed we did say that. Yes indeed it does make things worse...in the long term. Using dobutamine and milrinone to treat congestive heart failure has never been shown to reduce mortality and in fact, may indeed increase mortality, but these drugs certainly relieve symptoms in the short term. These drugs are given as IV infusions intermittently (for a few days) in advanced heart failure and only rarely continuously (for weeks or months) to a patient with really advanced heart failure waiting for a heart transplant or for palliative care (hospice).
Digoxin, dobutamine and milrinone are like giving the donkey a carrot to chase after:
Thank you donkey!
You have helped us all understand congestive heart failure physiology and treatment!
One more important note though. When we start ACE inhibitors/ARBs or beta-blockers for systolic congestive heart failure, we start at a low dose. Eventually, the body's natural response to blocking the RAAS or the sympathetic nervous system is to further increase the RAAS or sympathetic activity. This can overcome the effects of the medications! Well...we just slowly increase the dose of the drugs to a specific target dose. We increase the dose every 2 weeks or so as long as the patient feels fine without side effects and no worsened heart failure symptoms. We try to reach our "target dose" (different from drug to drug), which is where most people's RAAS and sympathetic nervous system will be adequately calmed down. Sometimes hypotension occurs and the target dose is not able to be reached, but at least we give it a try!
Last note is that the above mostly applies for systolic congestive heart failure. We don't use ACE inhibitors and beta-blockers as aggressively for diastolic congestive heart failure which is similar, but still a bit different.
Below is a summary image. Be sure the think of the donkey when you see a congestive heart failure patient!
- by Steven Lome