Mitochondrial Dysfunction and Symptoms of Heart Failure

Globally, approximately 64.3 million people living with heart failure which is why understanding the symptoms of heart failure and their relationship with mitochondrial dysfunction are crucial.¹ The most significant number of people (2% of adults) with heart failure are in developed countries like North America and the UK.¹

An important sign of heart failure is a decrease in one’s ability to engage in physical activity – this is referred to as exercise intolerance.² A factor that contributes to exercise intolerance is mitochondrial dysfunction.² Complications occur in the heart when the mitochondria don’t function as well as they should.  But why are the mitochondria so crucial in relation to heart failure?

Heart failure risk factors and symptoms

Heart failure is the chronic stage of any underlying disease that prevents the heart from pumping enough blood to meet the body’s needs.¹ The primary risk factors for heart failure are coronary heart disease, hypertension, type 2 diabetes, and obesity.¹ This means that an individual is more likely to experience heart failure if they have one of the previously mentioned conditions.¹ 

Symptoms of heart failure include shortness of breath, fatigue, and chest discomfort.³ Heart failure is a complex condition that multiple factors can cause over time.² As a result, there can be differences in the symptoms and signs that individuals with heart failure experience.² However, exercise intolerance is shown to be common in all cases of heart failure.²

The mitochondria

What are mitochondria? Mitochondria are small yet mighty organelles in mammalian (human) cells.⁴ Mitochondria are commonly referred to as the powerhouses of a cell due to their role in producing energy.⁴ The currency of energy used by the body is adenosine triphosphate (ATP).⁴ The ATP made in mitochondria powers all of the jobs that cells are required to perform.⁴ In the heart, the mitochondria are necessary for heart contraction and relaxation.⁴ 

What do mitochondria do during exercise?

When a healthy person exercises, inhaled oxygen travels to mitochondria in the heart and skeletal muscle cells.² This disbursement of oxygen increases the size and number of mitochondria, leading to the production of more ATP.² Through this process, the body can account for the extra energy needed during physical activity.² 

Unfortunately, if mitochondria can’t produce enough ATP, the heart can have serious complications.^2,4 In someone with heart failure, mitochondria are unable to produce enough ATP to keep up with the body’s energy demands during exercise.²  As a result, heart-related complications can occur.²

Targeting mitochondria for heart failure therapies

Thanks to advances in medical science and technology, people with heart failure live longer.¹ The survival rate for those diagnosed with heart failure is 20% greater than in the 1950s at the one-year and five-year follow-up but has remained steady since the 1990s.¹ Evidently, there is a need to develop more effective therapies for heart failure to increase the survival rate.¹ This is where treatments that target the mitochondria come into play.²

Research indicates that mitochondrial dysfunction has negative consequences for heart function.² A study published in the scientific journal Circulation suggests that directly targeting the mitochondria to improve their function may benefit individuals with heart failure.² In fact, this is the focus of new early-phase clinical trials hoping to further advance the survival statistics of heart failure.²

Why mitochondria impact heart health

As the site of energy production in cells, mitochondria play important roles in bodily processes such as pumping blood by the heart throughout the body.⁴ In the case of heart failure, mitochondrial size and number are reduced.² If mitochondria aren’t working correctly or there aren’t enough to cover the body’s needs, the essential chemicals and nutrients of life can’t be communicated. This lack of communication with the tissues like the heart, can lead to heart failure.^2,4 

Since mitochondrial function is impaired in those with heart failure, exercise intolerance can occur due to reduced oxygen use.² Exercise intolerance is the primary cause of complications. It can lead to a significant reduction in the quality of life for individuals with heart failure.² To improve heart failure symptoms and survival in patients, new treatments for heart failure are focused on targeting mitochondrial dysfunction.² 

References

1. Groenewegen A, Rutten FH, Mosterd A, Hoes AW. Epidemiology of heart failure. Eur J Heart Fail. 2020;22(8):1342-1356. doi:10.1002/ejhf.1858
2. Kumar AA, Kelly DP, Chirinos JA. Mitochondrial dysfunction in heart failure with preserved ejection fraction. Circulation. 2019;139(11):1435-1450. doi:10.1161/CIRCULATIONAHA.118.036259
3. Arrigo M, Jessup M, Mullens W, et al. Acute heart failure. Nat Rev Dis Primers. 2020;6(1):16. Published 2020 Mar 5. doi:10.1038/s41572-020-0151-7
4. Annesley SJ, Fisher PR. Mitochondria in health and disease. Cells. 2019;8(7):680. Published 2019 Jul 5. doi:10.3390/cells8070680