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Heart failure is when the heart doesn’t pump enough blood throughout the body. This doesn’t mean instant death, but the body starts wearing out around the edges. People with heart failure might feel short of breath and tired because there’s not enough oxygen reaching the brain and cells. Ankles and lower extremities might start swelling because the heart is unable to pull all of the blood up out of our legs. Sufferers understandably have trouble exercising. So what’s going on? Can anything be done about it?

Heart failure is an enormous problem. Tens of millions of people worldwide suffer from it, including at least 6 million Americans. It is the most common cause of hospitalization for adults over 65, and causes many repeat hospitalizations. Heart Failure severely reduces the quality of life, and comes with a high mortality rate. 

The causes of heart failure are numerous and can be difficult to identify; anything that impairs the heart’s ability to pump or deliver oxygen can be a contributing factor. Risk factors include:

• Coronary artery disease
• Smoking
• Obesity
• High blood pressure
• Diabetes
• Age
• Liver problems
• Kidney problems

To understand how these conditions may contribute to heart failure, we should first dive wholeheartedly into how the heart works. The heart is a muscle. It squeezes about once a second in a coordinated fashion. This squeezing pushes blood to and from the lungs, and to and from the body. We generally don’t get new heart muscle cells as adults. Instead, in order to react to changes in the needs of the body the heart cells themselves can grow (enlarge), as can the structure around and between the cells. A healthy heart may get stronger and more efficient in response to exercise or pregnancy A weakened heart, on the other hand, might change its structure by enlarging in response to stress, hormone changes, inflammation, and/or the risk factors listed above. These changes can result in a reduction of the amount of capillaries that supply the heart with blood, as well as fibrosis, chemical changes, and changes in the metabolism and organization of heart cells. But why would the heart do this? Is it rebelling against us? Is it something I said?

The heart loves us with its whole… self. It changes because it is trying its hardest and can’t manage to do it alone. When the heart senses it isn’t functioning properly, it may undergo cardiac hypertrophy. Cardiac is Greek (and Latin (and French)) for heart. Hyper- indicates an excessive amount, and -trophy is from the Greek word for nourishment, which in this case means growth. Cardiac hypertrophy is the excessive thickening or lengthening (or both) of the heart muscle. In pathological heart disease, scientists think this is initially an adaptive response. The heart attempts to compensate for dysfunction by increasing the size of the heart tissue. This works for a bit, right up until it doesn’t. Eventually, blood vessels can no longer reach all of the heart tissue. As a result, important chemicals like nitrous oxide are not produced and delivered to cells, connective tissue grows and stiffens, hormones get out of balance, and damaging inflammation occurs.

These maladaptive signs of heart failure give evidence as to why it’s so dangerous. Each of these responses to a stressed heart can also cause damage and restructuring of the heart. Inflammation is a great example. Consistent inflammatory chemicals in the body can spur the heart into a stress response that results in structural changes, which in turn may cause inflammation that spreads to other parts of the body. Similarly we can look at hormones like angiotensin, which regulate blood pressure by affecting how narrow your blood vessels are. An excess of angiotensin can narrow blood vessels and cause the heart to work harder, leading to thickening of the tissue. However, when the stiff tissue doesn’t pump blood efficiently the body responds by releasing more angiotensin in an attempt to help blood move through the body. Regardless of the initial cause, when the heart can’t keep up with the demands of the body, heart failure occurs.

So what can be done? Luckily, this problem has attracted some of the best minds on the planet (like our very own Dr. Michael Koren). Standard treatments aim to improve the quality of life and heart function in patients while reducing the incidence of hospitalization and mortality. Four classes of medications make up the standard of care (SOC) for heart failure:

• Those that affect angiotensin, such as

• • • Angiotensin converting enzyme inhibitor (ACE-inhibitor)
    • Angiotensin II receptor blocker (ARB)
    • Angiotensin receptor neprilysin inhibitor (ARNI)

• Beta blockers, which block stress hormones and help the heart relax

• Mineralocorticoid receptor antagonists (MRAs), which block the hormone aldosterone

• Sodium/glucose cotransporter 2 (SGLT2) inhibitors, which affect a host of cardiac functions

These SOC medications, though effective in many patients, are not perfect. While they tend to target and counteract the effects of wayward hormones,  they do not address underlying heart dysfunction or the changes to heart structure occurring beneath it all. There are many new medications that target a host of new mechanisms for fighting the scourge of heart failure. These include targeting the inflammation pathways or simulating the effects of relaxin. Relaxin is a natural hormone with many effects, including recycling extra structural material in the heart and increasing the efficiency of heart muscle at the tissue level. With luck (and the help of excellent, well-read volunteers like yourself), we can turn heart failure into heart success.

Staff Writer / Editor Benton Lowey-Ball, BS, BFA

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References:

Groenewegen, A., Rutten, F. H., Mosterd, A., & Hoes, A. W. (2020). Epidemiology of heart failure. European journal of heart failure, 22(8), 1342-1356. https://doi.org/10.1002/ejhf.1858

Lopaschuk, G. D., & Verma, S. (2020). Mechanisms of cardiovascular benefits of sodium glucose co-transporter 2 (SGLT2) inhibitors: a state-of-the-art review. Basic to Translational Science, 5(6), 632-644. https://doi.org/10.1016%2Fj.jacbts.2020.02.004

Murphy, S. P., Kakkar, R., McCarthy, C. P., & Januzzi Jr, J. L. (2020). Inflammation in heart failure: JACC state-of-the-art review. Journal of the American College of Cardiology, 75(11), 1324-1340. https://doi.org/10.1016/j.jacc.2020.01.014

Pandey, K. N. (2008). Emerging roles of natriuretic peptides and their receptors in pathophysiology of hypertension and cardiovascular regulation. Journal of the American Society of Hypertension, 2(4), 210-226. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739409/ 

Shimizu, I., & Minamino, T. (2016). Physiological and pathological cardiac hypertrophy. Journal of molecular and cellular cardiology, 97, 245-262. https://doi.org/10.1016/j.yjmcc.2016.06.001

Xie, Y., Wei, Y., Li, D., Pu, J., Ding, H., & Zhang, X. (2022). Mechanisms of SGLT2 inhibitors in heart failure and their clinical value. Journal of Cardiovascular Pharmacology, 10-1097. https://doi.org/10.1097/FJC.0000000000001380