The sooner heart failure is detected, the better. Suspect heart failure in patients with poorly-controlled or long-standing hypertension, valvular disease, or coronary artery disease. An echocardiogram can give an early indication of heart failure even in patients who don’t have symptoms. The diagnosis can often be confirmed with further testing, such as an exercise test.¹²³¹⁶

Heart failure develops with a snowball effect. Symptoms beget more symptoms. When the heart starts to fail, the body tries to compensate. As cardiac output decreases, the adrenergic system kicks in and norepinephrine levels increase. At first, the increased adrenergic stimulation helps maintain cardiac output. Over time the adrenergic stimulation starts to work against the heart. Norepinephrine increases arterial pressure. Eventually the heart must contract more forcefully to overcome increased arterial pressure. The increased norepinephrine also stimulates production of renin in the kidney. Renin is important in the conversion of angiotensinogen to angiotensin I. And angiotensin I is converted by angiotensin-converting enzyme (ACE) to angiotensin II. Angiotensin II further increases arterial pressure and causes structural changes in the heart. The structural changes are known as “cardiac remodeling.” Ultimately, these effects put additional stress on the heart, increase cardiac cell death, and cause disease progression.¹²³¹⁸

Many of the treatments used for heart failure target these processes…and ultimately slow the snowball effect. The goal of treatment is to slow the progression of the disease.

Only a few conventional treatments are actually proven to slow disease progression and improve survival. They fall into two categories: 1.) renin-angiotensin-aldosterone system (RAAS) blockers; and 2.) adrenergic system blockers.

To read more about heart failure guidelines see Pharmacist’s Letter / Prescriber’s Letter Detail-Document #180109.

• Angiotensin-converting enzyme (ACE) inhibitors
• Angiotensin II receptor blockers (ARBs)
• Spironolactone and eplerenone (Inspra)

People used to think ACE inhibitors (e.g., Monopril, Vasotec, etc) worked because they cause vasodilation and decrease arterial pressure. We now know that ACE inhibitors do more. They block production of angiotensin II, and that helps prevent cardiac remodeling. Treatment with ACE inhibitors improves symptoms and can decrease death rate by up to 23%.¹²³¹⁸

An angiotensin II receptor blocker (e.g., Atacand, Avapro, Cozaar, Diovan, etc) can be substituted for patients who can’t tolerate an ACE inhibitor. There’s growing evidence that these drugs also improve survival.¹²³²⁰

Spironolactone (Aldactone) is a potassium-sparing diuretic. It causes diuresis, but works in a unique way that also seems to interrupt one of the “snowball effects” of heart failure. Spironolactone blocks aldosterone. Aldosterone levels increase in patients with heart failure, which leads to fluid retention, fluid overload, and worsening of symptoms. Adding spironolactone to heart failure patients already on an ACE inhibitor and other diuretics can reduce symptoms and mortality by about 30%.¹²³²¹

An alternative to spironolactone is the newer drug eplerenone (Inspra). It works like spironolactone, but is more selective for aldosterone receptors…and therefore causes fewer side effects.

To read more about eplerenone see Pharmacist’s Letter / Prescriber’s Letter Detail-Document #191104.

Several natural medicines are promoted and used for cardiovascular conditions such as heart failure. Some of these products affect the renin-angiotensin-aldosterone system.

L-arginine is one of the best known natural medicines used for cardiovascular disease. The most common explanation for its cardiovascular benefits has to do with L-arginine’s affect on nitric oxide. L-arginine is a substrate for the enzyme nitric oxide synthase (NOS). The enzyme converts L-arginine to nitric oxide. This leads to vasodilation, improved coronary endothelial function, and increased coronary blood flow.^{110,116,1362,1363,3330}

In addition to increasing nitric oxide, there is some evidence that L-arginine decreases the activity of the angiotensin-converting enzyme (ACE).⁷⁸²⁰ Theoretically, this could have benefits in interrupting the snowball effect of congestive heart failure.

Despite these promising pharmacological effects, the clinical benefits of L-arginine are limited. When L-arginine is added to conventional treatment, heart failure patients seem to have improved kidney function and increase fluid elimination.³⁵⁹⁶ Some patients also have improved functional status, exercise tolerance, and quality of life, but these benefits have not been found consistently in clinical trials.^{3595,6028,7813,8014}

L-arginine seems promising, but there’s not much known about it’s long-term benefits…or if L-arginine can improve ultimate outcomes. For now, don’t recommend it for most patients. But if patients decide to try it, don’t worry too much, L-arginine is usually safe for most patients. Advise patients who use L-arginine that high doses are usually needed… 6-20 grams per day. Explain that adding L-arginine might cause a decrease in blood pressure. This could lead to hypotension in some patients, especially if they are taking other antihypertensives.

Pomegranate (Punica granatum) doesn’t sound all that appetizing to many of us. But pomegranate juice is now becoming a popular healthy drink. Products like POM Wonderful are being promoted by the fact that pomegranate juice has lots of polyphenols that work as antioxidants. There are more of these healthy polyphenols in pomegranate juice than in green tea, orange juice, or red wine.

But the evidence for cardiovascular benefits in humans is still just ramping up. There is preliminary evidence that it can decrease angiotensin-converting enzyme (ACE) activity. Some evidence also suggests that drinking pomegranate juice 50 mL/day might help decrease blood pressure by about 5% in patients with hypertension.⁸³¹⁰

Since pomegranate juice decreases ACE, there is potential for its use in heart failure. But so far this hasn’t been studied. If heart failure patients want to drink the juice, no problem. There’s no question that it’s a healthy drink. Just advise them not to rely on it for improved heart failure symptoms.

Beta-blockers are now considered essential in heart failure. We used to think beta-blockers would worsen heart failure, so clinicians weren’t using them. Now there’s proof that at least some beta-blockers (Coreg, Toprol XL, Zebeta) can save lives. Beta-blockers block the adrenergic system that revs up in patients with heart failure and can often lead to serious arrhythmias. Adding a beta-blocker can reduce mortality by up to 34%.¹²³¹⁸

Most patients should be started on an ACE inhibitor, even when they are asymptomatic. Beta-blockers should be added for improved prevention of disease progression and improved survival benefits.¹²³¹⁹ But don’t add beta-blockers in “decompensated” patients…those with pulmonary edema, etc. Beta-blockers can initially worsen these symptoms.

Some patients also turn to natural medicines to help with fluid retention. Several natural medicines are reported to have diuretic effects. Dandelion (Taraxacum officinale) is one of the most common herbal diuretics recommended for edema. Others include corn silk (Zea mays) and stinging nettle (Urtica dioica).

While tradition suggests that these herbs have diuretic properties, there is no reliable evidence that they reduce edema in patients with heart failure. Advise patients not to use them.

Thiamine and magnesium are sometimes recommended for heart failure patients who take conventional diuretics. That’s because diuretics can deplete levels of these nutrients.

Thiamine (vitamin B1) deficiency can worsen heart failure.^{1284,1285,1286,10507} This deficiency is most common in the elderly.¹⁰⁵⁰⁶ Elderly patients taking loop diuretics who continue to have symptoms despite adequate treatment might benefit from thiamine supplements.^{1284,1286,10508} Consider adding thiamine in these patients… 50-200 mg per day.

Magnesium deficiency is particularly concerning in heart failure patients who are also taking digoxin. Low magnesium levels can increase the risk of digoxin toxicity.^9613,9614 Consider checking magnesium levels in elderly patients who have been taking diuretics chronically. Also, make sure magnesium levels are checked in heart failure patients who have had arrhythmias…low magnesium levels could be a contributing factor. Add a magnesium supplement for patients who are deficient… 20-130 mg daily.⁶⁴³⁰

To read more about gender difference related to digoxin see Pharmacist’s Letter / Prescriber’s Letter Detail-Document #181203.

Several other plants contain cardiac glycosides…oleander, pheasant’s eye, squill, star of Bethlehem and others. Anecdotally, they may help,^15331,15332 but none of these have been studied in clinical trials…and none are appropriate for self-treatment of heart failure. Due to the lack of stringent manufacturing standards, these herbal products would likely contain an inconsistent amount of the active cardiac glycosides and produce inconsistent results. Fortunately, formulations of these plants are almost never found in supplements sold on store shelves.

Carnitine seems to have a positive inotropic effect, but it’s much different than the cardiac glycosides. Carnitine is an amino acid-like cofactor in skeletal muscles and the heart. It is involved in generating energy within the cells. Carnitine helps move long-chain fatty acids into mitochondria where they are converted to energy.

Patients with heart failure and other cardiovascular conditions seem to have decreased levels of this cofactor in heart tissue.¹⁵⁷² Some researchers think carnitine levels might be a disease marker for heart failure…lower levels usually indicate more severe heart failure.¹²³²³

The clinical evidence looks promising. Carnitine seems to improve symptoms, ejection fraction, and exercise tolerance. Carnitine seems to increase ejection fraction by up to 14% and exercise tolerance by as much as 21% in some patients.^{1575,1582,1583,3626} In some patients carnitine also seems to decrease cardiac remodeling.¹⁵⁷⁵

There’s even some preliminary evidence that carnitine might slow the disease process and improve survival.³⁶²⁵

The body of evidence supporting carnitine is growing, but it’s still fairly preliminary. There’s not enough support to recommend it across the board. But it might be worth a try in patients who are not improving on standard therapy. Some clinicians are using 1.5-2 grams, usually divided and given 2-3 times daily. Two different formulations are being used…L-carnitine and propionyl-L-carnitine. Both have been used in studies, but there’s some speculation that propionyl-L-carnitine might deliver carnitine to the cells more efficiently.¹⁴³⁹

Tell patients who take carnitine that it might take 2 weeks to a month for significant symptom improvement. Maximum improvement can take up to 6 months.

Creatine is a very popular sports supplement. Athletes often use it to bulk up or improve athletic performance. Now some people are using it in patients with heart failure…to improve exercise tolerance. There’s some evidence that it can help improve strength and endurance in heart failure patients.^4562,4563

But there are safety concerns with creatine and some unanswered questions. Creatine is probably not a good choice for patients with heart failure. Taking creatine requires drinking extra fluids to prevent dehydration and cramping. Fluid overload is a problem with heart failure patients. So increasing fluid intake is usually avoided. Also, people with heart failure are prone to renal disease. There is some concern that creatine might contribute to worsening renal function.^184,2118 Advise heart failure patients to avoid creatine.

Hawthorn (Crataegus monogyna) is an herb with a long history of use in Europe. Many clinicians in Europe consider hawthorn a preferred alternative to digoxin. Hawthorn seems to have many of the same benefits as digoxin. It increases cardiac output and exercise tolerance and reduces symptoms. Specific extracts of hawthorn (Crataegutt and Faros 300) seem to be helpful in the early stages of heart failure.^{8279,8280,10144,11449} But it might not offer much benefit in patients with more severe disease.

Hawthorn contains constituents that increase heart contraction and coronary blood flow, and cause vasodilation.^{406,10144,11450} Some people claim that hawthorn is actually better than digoxin. They say it’s less likely to induce arrhythmias, safer in renal dysfunction, and better tolerated overall. But there’s no solid evidence this is true.

You can think of hawthorn as a “milder digoxin.” It’s not appropriate for self-treatment. If you consider using it for your patients, hawthorn should only be considered early on in the disease, when symptoms aren’t too severe and BEFORE patients require digoxin. There’s no benefit to adding it in patients already taking digoxin. Doses of hawthorn extract are typically 200-500 mg three times daily. Keep in mind that it can take 6-8 weeks before there is maximal benefit. Tell patients that as symptoms get worse, they’ll eventually need to be switched to digoxin.

You might see patients trying another herb for heart failure…terminalia (Terminalia arjuna), also known as arjuna. There is some evidence it can improve heart function and decrease symptoms.²⁵⁰⁴ Some researchers think it might increase heart rate and cardiac output. Terminalia looks promising, but don’t recommend it yet. More evidence is needed about long-term safety and effectiveness.

THANKS TO THE NATURAL DATABASE.COM FOR THIS INFORMATION

To read more about using hydralazine plus isosorbide dinitrate for heart failure see Pharmacist’s Letter / Prescriber’s Letter Detail-Document #210105.

There is a lot of controversy about the effectiveness of coenzyme Q-10. Many cardiologists are skeptical. The reason is that some research findings are inconsistent. Early clinical studies are mostly positive. But recent studies are more negative. Most studies show that coenzyme Q-10 does NOT improve ejection fraction or exercise tolerance.^{5090,6037,6038}

But coenzyme Q-10 does seem to consistently improve SYMPTOMS…dyspnea, edema, etc. There’s even some evidence that coenzyme Q-10 can improve quality of life and reduce hospital admission rates.^{6407,6408,6409,8909,12170}

There isn’t enough strong evidence to recommend coenzyme Q-10 for all heart failure patients. But coenzyme Q-10 might be worth a try in some patients with heart failure, especially those with persistent symptoms. Consider adding it in patients who still have symptoms despite adequate treatment with conventional meds. Most clinicians use 100-200 mg, divided, and given 2-3 times daily.

There’s a good chance patients will ask about taurine. Taurine is an amino acid that is actually increased in the left ventricle of heart failure patients.⁹⁹⁰⁰ Researchers are finding that giving taurine supplements can help some patients. Taurine can improve cardiac output and decrease symptoms of heart failure when used for up to a year.^{5248,5271,5306,8221}

Researchers are still trying to figure out exactly how taurine works. But it seems to help regulate calcium movement in cardiac muscle cells. There is also evidence that it might have antioxidant effects, lower adrenergic stimulation, and decrease blood pressure.^{3467,8219,8221,8222} Each of these effects could help heart failure patients.

Most studies have been small and preliminary. As more evidence develops, taurine may become an important option for heart failure patients. But for now, there isn’t enough evidence to recommend it.

It’s true; natural medicines are NOT appropriate as primary treatment of heart failure. But some natural medicines may end up with a place in therapy…as adjunctive treatments.

There are a surprising number of beneficial natural medicines for heart failure. Several could be worth considering as add-on therapy in select patients…coenzyme Q-10, carnitine, and L-arginine.

There is growing evidence that some natural medicines may have a real role in therapy. But they are no substitute for standard treatments. Make sure patients are not attempting to self-treat heart failure. Ensure they are getting treatments proven to improve survival…ACE inhibitors, beta-blockers, etc. Patients adding on natural meds as adjunctive treatment should be monitored closely for signs of improvement or deterioration. These patients should also be watched for potential interactions.