CHF is being described as the next epidemic. Five million Americans have heart failure and up to 700,000 new cases are diagnosed every year. This illness causes one million hospitalizations and has a part in 250,000 deaths every year in the USA alone. Heart failure is the only heart condition actually on the increase.
Medicare spends more on CHF than it does on all forms of cancer combined. The yearly direct cost of CHF care is anywhere from 10 to 38 billion dollars US. Most of this cost comes from hospital stays for acute, or decompensated CHF.
The most common cause of CHF these days is ischemic heart disease. Ischemia is reduced blood flow, usually caused by blocked arteries. It accounts for 70% of heart failure cases in the USA. The next most common cause is idiopathic DCM in about 13% of patients, followed by high blood pressure in about 7% of patients.
Heart failure is a complex condition. Many symptoms are caused by reduced blood flow from a weakened heart. Further heart enlargement and weakening are caused by chemical messengers in the body called neurohormones. In heart failure, hyper-activity of the nervous system produces too many of these neurohormones - but this effect can be reduced by beta-blockers.
Another neurohormone that is too active in CHF is angiotensin II. Hyper-activity of the RAS (renin-angiotensin system) has a bad effect on the heart - but this effect can be reduced by ACE inhibitors.
About 7000 patients have been studied long-term in proper ACE inhibitor trials. ACE inhibitor patients show improved heart function, improved symptoms, and better test results. These studies also show a lower death rate from all causes by 20% to 25% and a lower risk of death and hospitalization by 30% to 35%.
The two landmark studies are CONSENSUS and SOLVD. Trial results show that all CHFers should take an ACE inhibitor if at all possible.
Beta-blockers block beta-receptors, which are located on the outside of heart cells. There are different kinds of beta receptors on heart cells. If a drug blocks all the beta receptors it can find, it is called "non-selective." If a drug blocks mainly one certain kind of beta receptor, it is called "selective." Coreg is non-selective. Toprol-XL is selective.
There is now a huge amount of evidence supporting beta-blocker use for CHF. More than 10,000 patients have been studied (medium-term, not long-term) in proper trials. Beta-blocker patients show improved heart function and often see their symptoms improve - but not always.
Beta-blocker studies show death from all causes lowered by 30% to 35% and risk of death and hospitalization lowered by 35% to 40%. Read more about beta-blockers at Jon's beta-blocker page.
One very bad effect of CHF is the way it "remodels" the heart's main pumping chamber - the left ventricle or LV. Remodeling is a reshaping of the heart into a rounder, larger shape and size. This makes the heart a less efficient pump. Remodeling can usually be stopped or reversed with proper drug therapies.
When the enlarged heart returns to a more normal shape, it is called "reverse remodeling." Reverse remodeling improves heart valve function and takes strain off the the heart's electrical system. Remodeling is further explained at Heartbytes.
While ACE inhibitors slow or even stop heart remodeling, studies have shown that beta-blockers can reverse it. All patients with mild to moderate heart failure should take a beta-blocker. Even patients with severe CHF should take beta-blockers if possible. This is clearly stated in the most recent guidelines for CHF therapy.
How do we estimate life expectancy for people with CHF in general? If you know an incidence and a prevalence, you can figure an average life expectancy. Prevalence is a snapshot in time - how many people have heart failure right now. Incidence is the number of newly diagnosed cases per year.
Total number of cases divided by number of cases diagnosed per year = years of life expectancy, in general.
CHF incidence (rate of new cases per year) isn't changing much, but the number of patients is going up. This is because people with CHF are living longer after being diagnosed. Our best guess from death certificates and hospital discharge reports is 400,000 to 500,000 new heart failure patients each year.
Incidence increases with age. For people 45 to 55 years old, CHF incidence is 1% to 2% per year but it is 10% for people over age 84. (Jon's note: Younger and younger people are getting CHF much more often these days. I will be proven right on this in a few years, unfortunately)
Prevalence (number of patients) is harder to guess. The best guess right now is that 4 to 5 million patients have CHF in America. If this is true, then average life expectancy is 10 years, but this is all guesswork.
In 1983 the average number of days a heart failure patient stayed in the hospital was 25 days. It was 19 days in 1993. Average length of stay has now gone down to 8 days but has not gone down in several years now. We kick them out of the hospital faster but so many more patients are coming into the hospital that the average number of hospital days stays the same.
Etiology refers to the causes of a disease. Why do people get CHF? Many possible CHF causes are listed near the top of The Manual. We know that it's a lot easier to prevent CHF than to treat it once a person has it.
Aggressively treating high blood pressure and CAD are the best ways to prevent heart failure. Persuading patients to stop smoking is also critical. However, once you have had a heart attack, you have a very high risk of getting CHF.
After a heart attack, a patient must be put on a beta-blocker unless he absolutely cannot take one. Regardless of where the lipids (cholesterol) level starts out, patients who aggressively lower their cholesterol do better. The goal is to get LDL under 130 mg/dL. Most patients should take an aspirin a day after an MI. Also, everyone who has an MI should have their EF measured because this may affect their treatment.
Pathophysiology is the set of changes caused in a person by a disease. What follows is a brief tour of what happens - and why - in heart failure.
In the standard or "hemodynamic" model of heart failure, there are many causes of CHF but once the heart is damaged for any reason, the same series of events almost always takes place.
When the heart is damaged, it pumps out less blood, which fires up the nervous system. Lower blood flow through the kidneys causes release of chemicals called renin and angiotensin II. Angiotensin II is a very strong vasoconstrictor. It causes the body to retain salt and water, which causes the body to produce a substance called aldosterone. The extra aldosterone makes the body retain salt and water even more, which leads to edema.
At first these reactions by the body are actually a good thing. Retaining salt and water increases the pressure in the heart, allowing it to beat more strongly. Epinephrine (adrenaline) levels skyrocket, speeding up the heart. Again, this is good at first, since it helps the heart keep up with the body's demand for blood.
When these responses keep up for awhile though, it's not good at all. The heart is working much harder than it is designed to do, and it begins to wear out, getting weaker. This is the "standard" concept of CHF's vicious cycle.
Any number of things can cause the heart to weaken, and this leads to the steps explained above. Hyper-activity of chemical messengers called neurohormones wreaks havoc on the weakened heart.
The body tells the heart what to do by way of chemical messengers called neurohormones. These neurohormones travel through the blood stream until they find a receptor they are attracted to. These receptors are on the walls of cells, including heart cells. When a neurohormone finds a receptor it likes, it attaches to it. Each type of neurohormone has receptors designed just for it. When a neurohormone connects with a receptor, that's when it has an effect on the cell. When too many neurohormones that like receptors on heart cells get too lively, it can dramatically change heart function.
The heart cell activity caused by these hyper-active neurohormones makes the blood vessels more narrow, increasing pressure; places extra strain on the heart by speeding it up too much; reduces proper functioning of the cells lining your blood vessels; and tells your body to retain sodium instead of peeing it out. All this causes edema. We also know that one neurohormone called norepinephrine is directly toxic to heart cells.
This becomes a deadly cycle that wears out the weakened heart. The worse one effect gets, the more it triggers the next effect, and so on. Another result of all this is remodeling.
Remodeling is a change in the shape of the left ventricle - the heart's main pumping chamber. It becomes rounder and larger. Remodeling has direct effects on heart rhythm and on pumping strength. Most of us think of large muscles as making us stronger, like a body builder. The heart doesn't work that way. In the enlarged heart many things change, including changes in the chemicals produced by the body.
So back to neurohormones. <g> These chemical messengers can also cause the release of more messengers; through a process called "gene expression." The most common "expression" is ANP (atrial natriuretic peptide) - overexpression of genes like ANP in the heart during CHF is not good for us.
ANP causes the body to eliminate salt through the urine - it is one of the body's "natural" diuretics. Normally, ANP is made by cells in the heart's upper chambers (atriums). In heart failure patients, however, ANP is also made by cells in the heart's pumping chambers (ventricles). This is a process that is normal in unborn children but not in adults.
In CHF, heart enlargement stretches the heart's walls. Long-term over-stimulation of these stretched heart cells causes a lot of things to happen that usually only happen in unborn children. Substances that should not be seen in the adult human heart are produced and have an effect.
These substances - often proteins - are designed to operate before birth, and are not well-suited to the adult. Their effects lead to larger, weaker heart cells. This "hypertrophy" is devastating in the long-term. It results in heart cells that do not function properly, and in cell death.
So normally, ANP is a good thing. However, in heart failure too much of it is made and in the wrong places, and that is not good.
Back to neurohormones! Keep in mind that for those of us with heart failure, the neurohormone called angiotensin II is not a good thing. It is a neurohormone that partly controls the cardiovascular system - a vasoconstrictor.
Angiotensin 1 is floating around inside all of us, healthy or otherwise. Angiotensin 1 is converted into angiotensin II by a substance in your lungs called ACE - Angiotensin Converting Enzyme. ACE is the enzyme we block with ACE inhibitors; Doing so prevents angiotensin I from converting into angiotensin II. Reducing angiotensin II stops a lot of vasocontriction from happening - and that's good.
However, angiotensin II is also made at other places in the body. So ACE inhibitors don't completely stop angiotensin II from being made. After starting an ACE inhibitor, there is a period where angiotensin II is almost completely stopped. Over time, angiotensin II levels rise again, from these "other" production methods. In other words, the body does what it wants and it is hard to stop it.
ACE inhibitors reduce production of angiotensin II. So it seems like a good idea to also block angiotensin II at other places. This means blocking angiotensin II receptors on cell walls. Remember that neurohormones don't have an effect until they attach to a receptor on a cell. The most important receptor seems to be the AT-1 receptor, although there is also an AT-2 receptor.
It is not really proven that using ARBs (Angiotensin II Receptor Blockers) to block the AT-1 receptor is a big help. It may be, but it is also true that by blocking this receptor, we may just cause the pesky old human body to use AT-2 receptors more. We just don't know.
So improperly produced ANP levels go up with heart failure, which is not good. Angiotensin II levels skyrocket and that's not good either. We also see higher levels of norepinephrine in CHF patients; That's a kind of adrenaline. High levels are seen in heart failure patients whether they have symptoms or not.
Norepinephrine levels aren't the only monkey wrench the nervous system throws at us in CHF. The heart's beta-1, beta-2 and alpha-1 receptors are affected by CHF. Coreg works on both beta receptors - 1 and 2 - while other beta-blockers only block one or the other. Coreg also works on alpha-1 receptors, which other beta-blockers do not.
Another class of substances not good in CHF is inflammatory cytokines. The best known is TNF-alpha (tumor necrosis factor-alpha). These cytokines weaken the heart's pumping action. TNF-alpha may be what causes the wasting or cachexia seen in patients with some types of cancer and also in some heart failure patients. High levels of TNF-alpha usually mean a poor prognosis.
Why TNF-alpha is over-produced in CHF isn't understood. Jon's note -A major TNF blocker trial has been stopped because it didn't help CHF patients. See www.chfpatients.com/CHFmeds.htm#tnf_stopped.
Nitric oxide (NO) is made from L-arginine by an enzyme called NOS (nitric oxide synthetase). Nitric oxide causes blood vessels to relax and widen, which increases blood flow and lowers blood pressure. The cells lining our blood vessels contain a type of NOS. The question is, "Is any of this important?" We don't know. Some people who have written on the subject are Douglas Mann, Bill Colucci, and Josh Hare.
Endothelin is a potent vasoconstrictor released by cells lining the blood vessels. Endothelin increases afterload - the resistance against which the heart must pump - by narrowing blood vessels. It also reduces the heart's pumping strength. The worse the heart failure, the higher the endothelin level. Drugs to lower endothelin levels are in trials. See the New CHF Meds page and IV Drugs page for more.
Natriuretic peptides are released when the heart enlarges. They help the body get rid of sodium, reducing edema. Like endothelin, these levels are high in all CHF patients. See the ANP section above for more.
Heart cells die in every cardiomyopathy. This may be cell death from a chronically poor blood supply or it may be apoptosis.
Apoptosis is "programmed" cell death. It is an active process that is important in cell division. Apoptosis is the reason why humans don't have webbed fingers, or gills. Early in our development, apoptosis helps see to it that cells form to handle specific duties in the body. It keeps cells doing what they are supposed to do, and no more.
Cells dying of apoptosis sort of "blink out" as they are swept away by scavenger cells. There is no inflammation and unlike regular cell death, apoptotic cells here and there just blink out and disappear. Of course, this sort of continued cell loss, regardless of cause, is not good!
We think that heart failure often begins with an event like a heart attack, where blood flow to the heart is drastically reduced. Heart cells (myocytes) die as a result (necrosis). The body's first response is to highly activate the RAS (renin-angiotensin system) and the sympathetic nervous system. These systems become hyper-active causing a "cascade" of neurohormonal changes.
The hyper-active neurohormonal systems cause more cell death, including programmed cell death (apoptosis). This further weakens the heart and causes remodeling - heart cells enlarge and stretch out of shape trying to strengthen the weakened heart.
This leads to improper gene production (expression), which stimulates even more neurohormone hyper-activity, leading to more cell death, and on and on, often leading to the person's death through pump failure, meaning the heart simply gives out.
So we see that heart failure is not just a problem with blood flow. This is a complex disease and it includes things occurring at a genetic level.
Not only do patients die slowly of progressive heart failure but SCD (sudden cardiac death) happens a lot. Besides remodeling of the heart "structure," there is also electrical remodeling. The heart's electrical pathways get stretched out of shape and chemically damaged. This makes arrhythmias much more likely.
SCD may be caused by VT (ventricular tachycardia) or VF (ventricular fibrillation). There are other causes of sudden cardiac death but VT and VF seem most common.. To run the heart's electrical system, the body basically trades an electrolyte inside a cell for a different electrolyte outside the cell. Swapping electrical charges this way "fires" the heart. That's why electrolyte levels are so important.
We think the root of the "electrical remodeling" problem is changes in this system of electrolyte exchange. The heart's stretching as it enlarges may cause fibrosis, further messing up the electrical pathways. There are contributing factors like too-low potassium and too-low magnesium levels caused by diuretics, too-high digoxin level, and class I antiarrhythmic drugs, which cause certain arrhythmias.
On top of all this, there are time relationships, so there are certain times of the day when patients are more prone to arrhythmias. Sudden cardiac death is a very complex concept.
Risk factors for developing CHF include CAD, previous heart attack, congenital heart disease, heart valve disease, high blood pressure, diabetes, being fat, alcoholism and smoking
As doctors we are often challenged by trying to diagnose heart failure. Consider the 30 year old man who comes to you with a cough - a significant cough that is worsening - and a little shortness of breath. What is the diagnosis? Bronchitis first comes to mind and you give the patient antibiotics. Note that for this patient, bronchitis really is usually the right call.
However, other things can cause a cough, and heart failure can be one of those causes. Other signs that the cause may be CHF are shortness of breath on exertion, mild edema, or even just unusual fatigue.
Other tell-tale signs may include a "swollen" jugular vein in the neck, a third heart sound, ascites, or a loud P2 (part of the second heart sound). The heart may be beginning to enlarge. Don't just listen to the lungs - you must also check heart size in your physical exam. If you are uncomfortable doing such an exam with your hand, get a chest x-ray or an echocardiogram to check heart size (and heart function if getting an echo).
Besides looking for heart enlargement, check for heart "stiffness." In some patients, EF can be normal but the patient has CHF due to diastolic dysfunction - a "stiff heart."
To diagnose CHF for sure, the simplest and cheapest test to do if it's available is an echocardiogram. However, the doctor who reads and interprets the echo must be skilled and experienced. It is even better if he knows the patient's history. We often change the diagnosis of patients referred to us when we repeat the echo. A doctor who is inexperienced or insufficiently trained in reading echos can easily make a mistake.
Echocardiogram is not the most accurate way to measure ejection fraction. A better choice for accuracy is the MUGA but MUGA does not measure valve disease or heart wall motion. Keep in mind that patient EF may not be as regular as we like to think; It may change from day to day. Ejection fraction is only one measure used to evaluate CHF. An MRI can give both an accurate EF and other important information in CHF patients.
Some patients - but not all - will need a right heart cath and some patients may need a heart biopsy. We don't biopsy every patient because results are not often worth the risk of the procedure. However, we see a few patients with suspicion of diseases like eosinophilic or giant cell myocarditis. We biopsy them because they may respond to steroids and other immunosuppressive drugs.
Sometimes we use a Swan-Ganz cath (done through the neck). There is risk with this procedure and it is expensive, so we only use the Swan-Ganz cath when a patient is very ill and we need specific blood flow and pressures information to adjust meds.
There is a new implantable device being tested. It measures and records pulmonary artery pressures, heart rate, and patient activity level at the time of each measurement. This device may be useful for monitoring patients day by day. The real question is whether having such detailed information will really help us improve a patient's quality and length of life.
Signs like rales (crackling in the lungs) may mean that a patient's heart is too weak to "keep up" - called "volume overload." However, because the lungs can drain very quickly in patients with chronic CHF - 4 to 5 times faster than normal - a person may be in volume overload without rales. A normal person with wedge pressure of 25 to 30 would be frothing at the mouth with fluid, but a chronic CHF patient may have no signs or symptoms with the same "numbers." Numbers alone don't mean all that much.
Just because a patient has dry lungs, no rales, and no third heart sound (S3) doesn't mean there is no volume overload. Samuel Butman looked at presence or absence of S3 and then measured wedge pressure. He found that even without an S3, a patient can have volume overload as likely as not. If there is no S3, flip a coin - they still may be wet.
One should check the neck veins for right-sided volume. A swollen or raised jugular vein, especially if the liver feels swollen, usually means right-sided volume overload. Most patients can be placed into one of 4 categories if they have heart failure:
Volume is an essential part of each CHF patient exam. It is very important to track which patients have signs of congestion and volume overload. Those signs may include orthopnea (have to sleep on pillows) and PND. It doesn't matter if they have no rales and no S3. Almost always, if CHF patients have orthopnea and PND, they have high left ventricle filling pressure. If they have ischemic heart disease (from blocked arteries), they may not have raised neck veins and still have congestion.
It is important to look for a swollen, enlarged liver. You can check liver size by feel. I usually feel how far down the liver is, in relation to the ribs. You must look for edema in the legs and ankles of course, but it can often be absent in a CHF patient with congestion. If a patient has a slightly enlarged heart and liver; and when you push on the liver the neck veins go up, this is called abdominal jugular reflux - a good way to check for congestion.
If we cannot prevent CHF, we want to improve patients' quality of life and prolong their life. The major factors in quality of life are shortness of breath and fatigue. We can control these by reducing fluid retention. To do that, we must recognize when a patient has volume overload and when he has low cardiac output. Let's look at some of the trials that have helped lengthen CHF patients' lives.
The modern era of CHF treatment began with the SOLVD and CONSENSUS trials, which reported on more than 4000 CHF patients who took either enalapril (Vasotec) or placebo. They were followed for up to 4 years.
SOLVD actually had two parts - a prevention trial and a treatment trial. The prevention trial had patients with an EF under 36% and no symptoms. At enrollment, patients could be taking digoxin (Lanoxin) for a-fib and a diuretic. The SOLVD treatment trial studied class 2 to class 3 CHF patients.
CONSENSUS enrolled class 4 CHF patients taking diuretics and digoxin. They took either placebo or enalapril (Vasotec). Like the class 2 to class 3 patients in SOLVD, CONSENSUS showed a lowered death rate in CHF patients taking an ACE inhibitor.
These trials established ACE inhibitors as primary therapy for CHF patients. Following these trials, we saw more and more evidence that all CHF patients should be taking an ACE inhibitor because they reduce death and hospitalization.
Still, in the class 2 to class 3 CHF patients in SOLVD, at 4 years 30% of the patients had died. In the class 4 CHF patients in CONSENSUS, mortality at one year was 50%. This is the same risk of death seen in many cancers, so even with ACE inhibitor use, we are not doing well.
How many lives will we save? Another way to look at these results is to ask how many patients you have to treat to prevent one death in 3 years. For the very sick class 4 patients in the CONSENSUS trial, you would have to treat only 6 patients over one year to prevent one death. In the class 2 to class 3 CHF patients in the SOLVD treatment trial, you would have to treat only 20 patients to prevent one death. In the class one patients in the SOLVD prevention trial, you would have to treat 104 patients to prevent one death.
The SAVE (Survival and Ventricular Enlargement) trial studied 2231 post-MI patients, mostly men without symptoms. All patients had an EF less than 41%. They took either placebo or captopril within several days after their heart attack. Captopril patients had a 19% lower death rate, fewer hospitalizations for CHF, and fewer of them went into heart failure.
Two other such trials should be noted: AIRE (Acute Infarction Ramipril Efficacy) - which compared ramipril to placebo; and TRACE (Trandolapril Cardiac Evaluation) - which compared trandolapril to placebo. Both trials studied post-MI patients with evidence of heart failure. They found that with ACE inhibitor therapy, only 14 patients had to be treated to prevent one death in 3 years.
It is now clear that all patients with left ventricle problems should take an ACE inhibitor. ACE inhibitors are the foundation upon which all the rest of CHF treatment is built.
The major concern in CHF patients taking ACE inhibitors is usually kidney function. CHF patients often have poor blood flow to and through their kidneys. Patients with low blood pressure, taking high diuretic doses, or who have diabetes are prone to weakened kidneys and should be closely monitored when starting an ACE inhibitor.
Does it matter what ACE inhibitor dose we use? Can we use 6.25mg of captopril twice a day? Do we have to push it to the doses used in trials?
I turn to the ATLAS trial This trial studied 3,164 class 2 to class 4 CHF patients (77% were class 3, with average EF of 23%). They compared 30mg lisinopril a day to placebo. However, all patients took 2.5 to 5mg lisinopril per day in addition to the trial dose/placebo.
At 4 year follow-up, ATLAS showed no difference in risk of death between the two groups. However, the higher dose group had fewer hospitalizations for heart problems. The lesson of ATLAS is that it pays to raise the ACE inhibitor dose in heart failure patients. This means seeing the patient frequently, monitoring their potassium levels, and following their blood creatinine levels.
NSAIDS (nonsteroidal anti-inflammatory drugs) are a big problem. Patients are put on diuretics to get rid of edema, which drives up their uric acid, which then causes gout. They are then put on indomethacin and 3 days later they are in the hospital with a creatinine of 5mg/mL. So managing gout in these patients is very tricky business.
I would not use indomethacin at all and I hesitate to use any NSAID at all. I prefer to use colchicine. If you are going to use an NSAID, use one that should have fewer side effects on the kidneys, like sulindac; Monitor the patient closely. Probably a short course of prednisone (40mg per day for 3 days, followed by a 5mg or 10mg per day taper) is best. Then get them on meds to prevent this from happening again.
ACE in the body converts angiotensin I into angiotensin II, which shrinks blood vessels - not good for CHF patients. There are several receptors on cell surfaces for angiotensin II, mainly the AT-1 and AT-2 receptors. With ACE inhibitors, we block that conversion of angiotensin I to angiotensin II.
Maybe it would be better to block the angiotensin II receptors themselves. That way, no matter how much angiotensin II there was, it couldn't do any harm, since there would be no receptors for it to connect with. We now have ARBS (ACE Receptor Blockers) that block the AT-1 receptor. These include Cozaar, Avapro, Diovan and Atacand.
Bert Pitt did much of the research in this area, and he reported results of ELITE (Evaluation of Losartan in the Elderly). The idea was that maybe ARBs would be better tolerated. ELITE studied 722 elderly patients taking either 50 to 100mg per day Losartan (Cozaar) [352 patients] or 50mg captopril (Capoten) 3 times a day [370 patients].
ELITE found no difference in risk of kidney failure. Another finding was that only 18% of patients stopped taking Cozaar (losartan) due to ACE cough, compared to 30% stopping Capoten (captopril) for ACE cough. A surprise result was lowered risk of death and/or hospitalization in losartan patients.
Does this mean we should switch our patients from ACE inhibitors to ARBs? No! The evidence does not support that. I use an ARB for patients who cough when taking an ACE inhibitor or who cannot tolerate an ACE inhibitor for some other reason. The alternative is using isosorbide dinitrate with hydralazine, which many patients find hard to tolerate.
Diuretics are the major treatment for CHF congestion (edema). The important concept to remember is "sequential nephron blocking." This means using a loop diuretic to block the ascending limb of the loop of Henle (in the kidney).
If this isn't enough, add something else - maybe a thiazide such as Zaroxolyn (metolazone) - to block the distal convoluted tubule of the kidney.
Diuretic side effects are well known: low blood sodium level, low blood potassium level, racing heart rate, and low blood magnesium level, among others. Thiazide diuretics can cause increased cholesterol and blood sugar levels.
Our goal is to reduce filling pressure in the heart. For some reason, many doctors think CHFers need a little extra fluid to maintain preload. This is wrong.. A wedge pressure of 20mmHg is not necessary. A wedge pressure of 12mmHg is probably fine. Of course, there are exceptions to every rule so we must always be careful.
The only trial of diuretics in heart failure with mortality as an endpoint was RALES. This trial studied the effects of spironolactone on risk of death in class 3 to class 4 CHFers. Aldactone is an aldosterone antagonist (blocker). It was added to standard CHF therapy of ACE inhibitor and a loop diuretic like Lasix. Most of the patients were also taking digoxin (Lanoxin).
Results showed a 27% reduction in mortality and a 22% reduction in non-fatal hospitalization and total mortality. It seems that spironolactone is important for CHF treatment. The main side effect is painful and swollen breasts - in both men and women.
What about digoxin (Lanoxin)? The DIG (Digoxin Investigators Group) trial was a very large study that put 3000 patients on placebo and 3000 on digoxin, then watched all-cause mortality. The fact that there was no difference whatsoever between digoxin and placebo makes one ask why this trial is important.
The results are important because digoxin is the only drug that makes the heart beat more strongly which has been proven not to kill patients. Also, patients felt better and hospitalization for heart failure went down in the digoxin group.
There were 2 trials before the DIG trial, in which patients were stable on digoxin and other meds, then digoxin was either withdrawn or continued. Patients who had digoxin withdrawn were rehospitalized more often.
I prescribe digoxin. The DIG trial showed that mortality increased when digoxin levels were too high, so that level must be monitored. I use a rather simple method to figure proper dose. I look at the patient and if they are older or smaller than I am, they get 0.125 mg per day. If they are bigger and younger than I am, they get 0.25 mg per day. I check their digoxin level in about 7 to 10 days to make sure that their level is less than one microgram/mL and I try to keep it there.
There are things that cause ultra-sensitivity to digoxin. These include abnormal potassium, magnesium or calicum level; thyroid disease, kidney failure, lung disease, and some other drugs, especially amiodarone. When I start a patient on amiodarone, I drop the digoxin dose in half immediately, because amiodarone will cause a rise in digoxin levels. Again, I check the level in 7 to 10 days.
Digoxin is an important tool in heart failure treatment. Although dig level must be monitored, it may not be necessary to check digoxin levels every time you see a patient.
Some drugs increase risk of death. These include some inotropes such as milrinone, dobutamine, xamoterol and ibopamine. Basically every inotropic drug which has been studied - with the exception of digoxin - increases risk of death (mortality). There are also vasodilators that increase mortality: flosequinan is one which actually received FDA approval before it had to be withdrawn from the market.
Certain calcium channel blockers such as Covera (verapamil), Procardia (nifedipine), and Cardizem (diltiazem) should not be used in heart failure patients, even if the patient has CAD. If you just have to use one, use Norvasc (amlodipine) or Plendil (felodipine); these two do not increase hospitalization rate or mortality.
Beta receptors are a spot on cell walls designed to receive a beta-type chemical messenger called a neurohormone; Sort of like an electrical plug in a wall socket, with the wall socket being the beta receptor. Beta-blockers intentionally block that wall socket so your beta-receptors can no longer accept the chemical messengers they are designed to accept. There are 2 main kinds of beta receptors on cells: beta-1 and beta-2 receptors.
Some beta-blockers are "non-selective." These drugs block both kinds of beta receptors. Other beta-blockers are "selective." These drugs block only beta-1 or beta-2 receptors but not both. Coreg is non-selective and blocks both beta-1 and beta-2 receptors. Toprol XL is selective for beta-1 receptors and only blocks those. Both are good for heart failure. Which is better? I don't know. It depends who you ask.
Carvedilol Heart Failure Experience - In all 4 parts of this trial, patients had an EF under 35%, heart rate over 68 and systolic blood pressure over 85. Amost all were taking ACE inhibitors and diuretics, and most were also on digoxin. Patients were in 3 groups: mild, moderate, or severe heart failure.
All 3 groups had their dose raised, but the endpoints were different. In the mild heart failure trial, the endpoint was whether the disease got worse. In the moderate heart failure trial, the endpoint was exercise tolerance. In the severe heart failure trial, the endpoint was quality of life.
The trial was stopped early when it became apparent that whether you were class 2 or class 3, Coreg gave a survival advantage and reduced heart-related hospitalizations. However, this is not the complete story. The PDR (Physicians' Desk Reference) still says that beta-blocker use is, "contraindicated in heart failure." That's because when first started, beta-blockers cause a fall in heart function.
However, if you start with the smallest possible dose and raise it slowly and carefully, you will probably see patients' EF go up and their heart size go down - "reverse remodeling." Mortality is reduced.
CIBIS and MERIT-HF studied beta-1 blockade in a large number of CHF patients. The first CIBIS trial was small but showed a trend toward benefit.
The second CIBIS trial studied 2,647 mostly male, elderly, class 2 to class 3 CHF patients, who had an average EF of 26%. They took either bisoprolol (a beta-1 blocker) or placebo. Almost all patients were also taking an ACE inhibitor. The results showed lower all-cause mortality and fewer hospital admissions in bisoprolol patients.
MERIT-HF enrolled 3,991 mostly male, elderly, class 3 to class 4 CHF patients, who had an average EF of 28%. The results showed a 34% relative reduction in total mortality.
There are a number of CHF beta-blocker trials either recently ended or underway. These include BEST, COPERNICUS using Coreg in class 4 patients, and COMET (Carvedilol Or Metoprolol European Trial).
Since beta-blockers benefit CHF patients, which one should we use? We know that Coreg blocks both beta receptors and also blocks alpha receptors (which helps expand blood vessels); metoprolol (Toprol XL) and bisoprolol (Zebeta) block only beta-1 receptors.
It seems reasonable that blocking both beta receptors would be better. However, we really don't know this for sure; It is currently being tested in COMET. We have no real evidence saying one or the other is better. Both selective and non-selective beta-blockers drop blood pressure, drop wedge pressure, and raise heart output after about 3 months or so, but that's all we know for sure, comparison-wise.
The question is, which drugs should be used to treat whom, and when? For patients with decompensated heart failure (severe symptoms), the key may be edema, for which loop diuretics like Lasix are the main therapy. It makes sense to add digoxin at this point, and you may want to use an inotrope during the patient's hospital stay. An inotrope will improve quality of life and speed up fluid loss. You should also begin an ACE inhibitor. Beta-blockers should not be started in a patient while their symptoms are severe.
For patients whose symptoms are not bad, the main concern should be remodeling. We want to shrink the heart back down to its normal, healthy size. Such patients should already be taking an ACE inhibitor, and now is the time to add a beta-blocker. I start beta-blockers either at the very end of the first hospital stay or as an outpatient. Patients start on a very low dose and raise it slowly. Finally, you might want to think about adding spironolactone (Aldactone).
Due to the limited number of donor hearts, the therapy of last resort for the heart failure patient is heart transplant. Before we consider transplant for a CHF patient, we want to be sure that all other therapies have been considered.
It is important to remember that this is not a simple disease. I would stress the necessity of a complete exam and workup for all new heart failure patients. We should find the cause of CHF because this may alter your approach. For example, if blocked arteries are found, angioplasty may be one of the first treatments considered.
The first rule of heart therapy is to begin therapy based on a specific diagnosis, if at all possible. In addition to drug and non-drug therapies, invasive therapies may be needed. These may include:
In summary, I would recommend the following approach for a patient with heart failure:
We need to remember that at the root of all this talk is not a disease, but a patient - a person. This is crucial. I refer to Dr. Phil Tumulty, who wrote a book called The Effective Clinician. On page 3, he says: "A pair of kidneys or a heart will never come to the doctor for a diagnosis and treatment. They will be contained within an anxious, fearful, wondering person, who is asking puzzled questions about an obscure future weighed down by the responsibilities of a loved family, with a job to be held and with bills to be paid."
All information on this site is opinion only. All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor. Use the reference information at the end of each article to search MedLine for more complete and accurate information. All original copyrights apply. No information on this page should be used by any person to affect their medical, legal, educational, social, or psychological treatment in any way. I am not a doctor. This web site and all its pages, graphics, and content copyright © 1997, 1998, 1999, 2000, 2001, 2002, 2003, 2004 Jon C.