Cole Jensen, Mayo Clinic Cell and Regenerative Physiology Laboratory, US, winner of The Physiology Society prize draw at Experimental Biology 2022, Philadelphia, US
HFpEF is a condition that stiffens the heart making it difficult to fill with blood. Like the difference in effort required to fill a football with air requiring a pump, rather than easily blowing up a balloon with the mouth. A healthy heart should act like a balloon. Cole Jensen discusses the rise of this heart condition among an ageing population and the efforts being made to treat the global health problem.
I have always been amazed by how the human body functions and how it all just seems to “work”. From organs to cells to molecules, everything fits together in an intricate dance to keep us up and running. My appreciation for this dance ultimately inspired me to pursue a career in medicine.
Before I set out on that path, I wanted to explore some of the “why” behind our intricate physiology. That exploration led me to take on a post-baccalaureate research position at the Mayo Clinic, Minnesota, US. Here, at the intersection between groundbreaking research and world-renowned medicine, I have come to appreciate one simple yet profound fact. We are getting older.
Around the globe, humanity finds itself amid a profound demographic transition, with the proportion of individuals aged 65 and older increasing rapidly. This fact was emphasised when, for the first time in human history, this group outnumbered children younger than five in 2018 (1). Thanks to modern medicine’s incredible and ongoing efforts, these trends will undoubtedly continue. And as they do, the face of medicine will change with it.
Heart health and ageing
As we get a closer look at that face, we will see more diseases that predominantly affect older patients. Today, one of the starkest features is the rise in heart failure with preserved ejection fraction (HFpEF). HFpEF is a condition that reduces the amount of blood the heart can circulate by hindering its ability to fill up.
This means each contraction successfully pumps out more than half of the blood in the left ventricle, but the volume of blood circulated is insufficient to meet the whole body’s needs. HFpEF functions opposite to its better known cousin, heart failure with reduced ejection fraction. In this condition, the heart struggles to pump out blood instead of filling, ejecting less than half of the blood in the left ventricle (2).
Addressing an unmet healthcare need
The distinction between heart failure with preserved and reduced ejection fraction may seem trivial; however, they could not be more different from a treatment standpoint. Numerous treatments for HFrEF are available to patients, but there has yet to be a single treatment for HFpEF that has succeeded in reducing the risk of mortality (3).
The lack of effective therapies is not due to a lack of need. Close to half of the five million patients in the US with heart failure have preserved ejection fractions, and its prevalence is increasing relative to HFrEF. There is a substantial unmet need here and the prevalence will continue to grow for years to come.
Who is most at risk?
HFpEF overwhelmingly affects older patients, and advanced age is the most significant risk factor. It is also more common in females than males, and comorbidities like hypertension, obesity, and diabetes also increase the risk of developing the condition.
For those living with HFpEF and its comorbidities, quality of life is significantly reduced. Patients typically experience exercise intolerance and difficulty catching their breath, which significantly reduces activity. Other heart conditions like atrial fibrillation are common and further complicate patients’ health (5). The enormous burden of living with HFpEF results in high hospitalisation and mortality, with five-year survival rates of less than 50% (4).
The road ahead for effective medical therapies
Research into HFpEF has been steadily growing. The challenge is, just like an iceberg, there is much more going on under the surface than it appears. There is a complex combination of dysfunction in multiple organ systems throughout the body, in addition to the impaired cardiac output. Furthermore, few patients have the same combination and severity of these impairments, resulting in a patient population with significant variability (6).
These differences make it incredibly difficult to create animal models that replicate how the disease works in humans. The scarcity of animal models to study the condition stands as the most significant barrier to progress (7). It is not easy to create a working model either. For an animal model to have a chance to provide insight into effective treatments, they need to consider multiple levels of organ dysfunction, which becomes exponentially more challenging to develop.
Striving to overcome clinical obstacles
Despite the challenge, hard-earned progress is being made in understanding the mechanisms behind HFpEF. New animal models, even some from my own lab, are being used to tackle this problem (8,9). Continued research with current and future animal models will inevitably result in breakthroughs that lead to effective treatments. When exactly that will happen is unclear, but for the time being, I am excited to keep pushing.
References
- United Nations, Department of Economic and Social Affairs, Population Division (2019). World Population Prospects 2019: Data Booket. ST/ESA/SER. A/424
- Simmonds SJ, Cuijpers I, Heymans S, Jones EAV. Cellular and Molecular Differences between HFpEF and HFrEF: A Step Ahead in an Improved Pathological Understanding. Cells. 2020 Jan 18;9(1):242. doi: 10.3390/cells9010242
- Borlaug BA, Colucci WS. Treatment and prognosis of heart failure with preserved ejection fraction. UpToDate (pristupljeno 23.2. 2017.)
- Andersson C, Vasan RS. Epidemiology of heart failure with preserved ejection fraction. Heart Fail Clin. 2014 Jul;10(3):377-88. doi: 10.1016/j.hfc.2014.04.003
- Gazewood JD, Turner PL. Heart Failure with Preserved Ejection Fraction: Diagnosis and Management. Am Fam Physician. 2017 Nov 1;96(6):582-588
- Borlaug BA. Is HFpEF One Disease or Many? Am. Coll. Cardiol. 2016 Feb;67(6):671-673
- Roh J, Houstis N, Rosenzweig A. Why Don’t We Have Proven Treatments for HFpEF? Res. 2017 Apr 14;120:1243-1245
- Han YS, Arteaga GM, Sharain K, Sieck GC, Brozovich FV. Rat Model of Heart Failure With Preserved Ejection Fraction: Changes in Contractile Proteins Regulating Ca2+ Cycling and Vascular Reactivity. 2021 Oct 18;144:1355-1358
- Riehle C, Bauersachs J. Small animal models of heart failure. Res. 2019 Nov 1;115(13):1838-1849