Heart failure develops when cardiac muscle becomes weakened.
The term heart failure covers a broad array of causes and symptoms, with the common denominator being reduced capacity of the heart to deliver the necessary amount of blood to the rest of the body to enable normal physiological function. The most common symptom of heart failure is the accumulation of fluid in the lungs, so the term congestive heart failure has become almost synonymous with heart failure.
Heart failure reduces exercise capacity, which in turn leads to progressive muscle weakness and a vicious cycle of sedentary behavior and weight gain, with subsequent development of metabolic abnormalities such as diabetes. Loss of muscle mass and function is prominent in heart failure patients.
Most individuals over the age of 65 have some degree of heart failure, or stage 1 heart failure, which is characterized by shortness of breath during recreational exercise activities. Stage 1 heart disease is not usually diagnosed as a significant clinical problem. Stages 2, 3, and 4, however, are much more serious and may significantly impair the ability to perform activities of daily living, and ultimately cause death.
Two Principal Forms of Heart Failure
There are two principal forms of heart failure.
Systolic heart failure (or heart failure with reduced ejection fraction (HFrEF)) is caused by a lowered ability of the heart to pump out blood because the strength of contraction of the heart muscle declines.
Surprisingly, more often the contractile capacity of the heart is not affected or is only slightly impaired. In this case, heart failure is caused by an inability of the heart muscle to relax after contraction. The ability of the heart muscle to relax after contraction is important so that the heart can fill up with blood before the next contraction. This form of heart failure is termed heart failure with preserved ejection fraction (HFPEF), and it is the predominant form of heart failure worldwide. Not only are there different types of heart failure, but there is also a wide range of potential causes of heart failure, including the natural process of aging.
Pharmaceuticals for Heart Failure Treatment
Treatment of the underlying cause of heart failure is, of course, optimal. Pharmacological treatment of heart failure predominantly targets the ability of the heart to contract. A variety of drugs may be used for the purpose, with varying degrees of success. However, treating heart failure pharmacologically may be quite complex, particularly in the elderly, who most commonly suffer from heart failure. More than 50% of individuals over age 65 with heart failure have at least four other significant health problems that may also require pharmacological therapy. These additional conditions and therapies may complicate heart failure therapy. Adverse responses to pharmacological heart failure therapy are not uncommon, including the fact that the most common drugs for heart failure treatment (ACE inhibitors and beta blockers) can adversely affect muscle function.
FACT: Despite the expenditure of millions of dollars and years of time and effort, not one large-scale clinical study of a single drug therapy has demonstrated a substantial beneficial outcome for the most common form of heart failure in which the principle problem is the failure of the heart to relax after contraction.
This disappointing reality may reflect the difficulty of treating a syndrome with diverse causes, pathological responses, and multiple chronic diseases using an entirely drug-oriented approach.
Skeletal Muscle Function and Heart Failure
There are multiple reasons for impaired physical functional capacity in heart failure. Most attention has focused on the inability of the heart to pump an adequate amount of blood, with a consequent limitation in the delivery of nutrients and oxygen to the skeletal muscles. Most heart failure treatments are aimed at improving cardiac function. Unfortunately, drugs that target cardiovascular function have often failed to influence exercise capacity.
Heart failure also induces adverse responses in skeletal muscle that go on to negatively impact physical function. Science has shown that physical training in individuals with heart failure can improve exercise tolerance by improving skeletal muscle function, even if heart function is not improved. Testosterone treatment, which enhances skeletal muscle function but does not affect heart function, has also been shown to improve exercise capacity in heart failure patients. Therefore, it is evident that while impaired pumping action of the heart plays a central role in heart failure, so, too, does impaired skeletal muscle function.
Deficiencies in skeletal muscle function are common to all forms of heart failure, and it is becoming clear that these deficiencies play an important role in pathophysiological responses.
Three aspects of skeletal muscle function are altered in heart failure:
- Muscle protein breakdown is accelerated, which results in a loss of muscle mass. Heart failure induces a loss of muscle mass and strength. The loss of muscle mass is often not evident since many heart failure patients are overweight or obese, although in end-stage heart failure the loss of muscle becomes painfully obvious. The loss of muscle mass and strength in heart failure occurs in large part because the body’s normal response to dietary protein is altered. In healthy individuals, dietary protein stimulates the production of new muscle protein. In heart failure patients, conventional dietary intake has little or no beneficial effect on muscle protein. This is called anabolic resistance.
- The organelles in muscle where energy is produced (mitochondria) don’t function normally. The capacity of skeletal muscle mitochondria to produce the energy needed to perform physical activity is impaired in heart failure—specifically, the ability to oxidize fatty acids for energy. This is in large part due to a deficiency in the ability of fatty acids to enter the mitochondria. Incomplete oxidation of fatty acids leads to the accumulation of products in muscle that impair normal metabolic function.
- The normal regulation of the amount of blood flow to muscles is disrupted. The amount of blood that is supplied to muscle tissue is normally tightly tied to the metabolic demand of muscle. When the demand for oxygen and energy substrates increases with exercise, blood flow to muscle increases proportionately. The normal increase in muscle blood flow that occurs during exercise is reduced in heart failure. The diminished ability to appropriately regulate muscle blood flow in heart failure is due to the decreased production of nitric oxide (NO), the principal vasodilator in skeletal muscle that helps to widen blood vessels and increase blood flow.
Thus, whereas decreased capacity of the heart to deliver adequate blood to peripheral tissues clinically defines heart failure, diminished skeletal muscle mass, strength, and oxidative capacity play important roles in the impairment in physical function.
Amino Acids and Heart Failure
We’ve seen how heart failure can send patients into an anabolic resistant state. A balanced mixture of essential amino acids (EAAs) can help overcome anabolic resistance in heart failure.
Many studies have led to this discovery. Let’s highlight the key findings.
- It was first shown that only essential amino acids (EAAs) are necessary to promote muscle protein synthesis (the building of muscle protein). Check out this study my colleagues and I published in the American Journal of Clinical Nutrition.
- In a study we published in the American Journal of Physiology-Endocrinology and Metabolism, it was then shown that a formulation of concentrated EAAs overcame anabolic resistance and stimulated muscle protein synthesis. The action of any one or sub-group of EAAs was not effective. For example, neither the three branched-chain amino acids (leucine, isoleucine, and valine) nor leucine alone is ineffective, as evidenced by a 2017 study published in the Journal of the International Society of Sports Nutrition.
- Finally, a balanced mixture of EAAs effectively stimulated muscle protein synthesis in heart failure patients who were completely resistant to any beneficial effect of a popular meal replacement beverage designed and marketed specifically for support of heart failure patients.
Specific Amino Acids for Heart Failure
Although not an essential amino acid, citrulline is an amino acid that, when added to a mixture of EAAs, targets the impaired regulation of blood flow to the muscle in heart failure. Consumption of the amino acid citrulline is the most effective way to promote nitric oxide production, the key to increasing blood flow to the muscle during activity.
Dietary supplementation with arginine can also be an effective approach to increasing nitric oxide production. However, there are limitations in the use of supplemental arginine. Because of rapid uptake and the metabolism of arginine in the liver, a large dose of arginine is necessary to significantly increase nitric oxide production, and this can cause significant gastric distress. In contrast to arginine, citrulline is well-tolerated and has been shown to stimulate nitric oxide production effectively in individuals with heart failure.
We’ve discussed how the limited capacity of skeletal muscle mitochondria to produce energy in heart failure directly impacts the ability to perform physical activity. The deficiency in fatty acid oxidation is particularly problematic, because the oxidation of fatty acids provides the energy for the performance of low-intensity exercise that corresponds to the activities of daily living. Amino acid consumption can address several aspects of mitochondrial function. EAAs stimulate the production of enzymes in mitochondria that are involved in the metabolic reactions that produce energy. In addition, the EAA leucine stimulates the production of new mitochondria, and the amino acid carnitine can improve the transport of fatty acids into the mitochondria.
In summary, consuming specific amino acids as dietary supplements can address the three major ways that heart failure impairs muscle function: (1) accelerated breakdown of muscle protein, (2) poor regulation of muscle blood flow, and (3) impaired production of energy.