Brian Martin, PhD

 and other cardiovascular diseases, were introduced as major contributors to mortality each year in the US. Heart failure occurs when the heart can no longer meet the demands of the rest of the body, and is often associated with, and occurs alongside, other cardiovascular diseases such as coronary heart disease, heart attack, hypertension, overweight, obesity and diabetes.

Of the predominating risk factors or comorbidities

 that occur alongside HF, hypertension appears to be the most prevalent, followed by coronary heart disease and stroke.

Importantly, it appears that certain conditions can worsen comorbidities, such as overweight and obesity increasing the risk of developing hypertension, thus increasing risk of HF. Further, comorbidities such as hypertension 

This occurs as increased pressure requires extra effort by the heart to pump blood to the body, resulting in compensatory hypertrophy and dilated cardiac chambers that can no longer relax or contract effectively, 

. Similarly, coronary heart disease can result in myocardial infarction, damaging the heart and killing cardiomyocytes, which cannot regenerate, resulting in scarring and replacement fibrosis, leading again to reduced ability of the heart to relax or contract, ultimately leading to HF.

These insights indicate that preventative measures are needed early on to halt the progression of risk factors to full on cardiovascular disease leading to HF. As such, for certain HF conditions (e.g. HF with preserved ejection fraction, or HFpEF), 

 that the best way to treat the condition is to focus treatment on comorbidities, as no effective therapy exists for HFpEF.

In many patients with HFpEF, non-cardiovascular related deaths are often more common that HF deaths, and thus treatment of comorbidities including smoking, diabetes and pulmonary diseases, should be used as therapy.

As mentioned above, hypertension is a common comorbidity of, and primary driver for, HF development, and thus provides one avenue of early treatment for HF prevention. In sum, treatment of conditions which progress to HF exhibit compelling starting points for HF prevention.

At least as early at 2011, researchers have predicted increased HF and cardiovascular disease occurrence and rising health care costs associated with cardiovascular diseases, estimating that at least 40% of Americans will suffer from some form of cardiovascular disease by the year 2030. The total, direct medical costs of cardiovascular diseases is expected to increase by 200% to $818 billion dollars, while indirect costs (those associated with missed labor, etc.) are expected to rise by 61% to $275 billion dollars.

A primary cause of increased costs associated with cardiovascular disease is an aging population, which marks an improvement in patient survival and longevity, even if those extra years alive are not disease free. An increase in longevity but not health may be partly explained by a healthcare system designed to treat symptoms of HF as they present, and not treating underlying causes of the disease, thus prolonging life, but not curing the disease.

Further, a large and rapid increase of diabetes, overweight and obesity in the population is thought to contribute to rising cardiovascular disease occurrence and costs, which may increase medical costs more than predicted.

Considering these dramatic predicted increases in cardiovascular disease and associated diseases including hypertension, diabetes, overweight and obesity, and increasing medical costs and lost labor, the next article will discuss preventative measures to aid in reduction of cardiovascular diseases among those at high risk, both young and aged.

Brian Martin is a post-doctoral research fellow at Baylor College of Medicine studying heart failure and atrial fibrillation. The opinions expressed in the piece here are solely those of the author, and do not reflect those of the publication.

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Of the predominating risk factors or comorbidities that occur with HF, hypertension appears to be the most prevalent.

Risk Factors, Comorbidities, and Costs of Heart Failure

 published by the National Institutes of Health (NIH) shows 

 as the no. 1 killer, as of 2015, with an associated 1.4 million deaths in the US. Cancer, the next most lethal field of diseases, was the cause of death in approximately 650,000 individuals in the same year, less than half of that linked to cardiovascular disease.

, or the inability of the heart to provide the body with enough blood and oxygen for the body to function properly, is the common end-stage condition of many cardiovascular disease. The Centers for Disease Control and Prevention (CDC) report that 5.7 million patients are afflicted with HF and of those, 50% will die within 5 years of diagnosis.

In addition, HF increase patient morbidity and treatment costs upward of $30.7 billion total annually.

Though it contributes the majority of deaths in the US, reduces patient quality of life, and increases health costs, cardiovascular disease actually does not rank in the top 25 (no. 27) in funding dollars allocated to its research. And despite best efforts of researchers and clinicians, a five-year, 50% mortality rate is too high.

But what exactly is HF, and what makes treating it so difficult?

Heart failure is broadly characterized by the inability of the heart to meet the demands of the body, which may result in congestion, chest pain, reduced ability to perform daily function without fatiguing, and death as the heart muscle fails.

More specifically, there are different classifications of HF.  Is the patient’s HF chronic or acute? Is it compensated or decompensated? Has the patients’ HF reduced the fraction of blood ejected from the heart during each contraction (HF with reduced ejection fraction [HFrEF]) or is the ejection fraction preserved (HFpEF)?

Finally, does the patient have comorbidities, such as hypertension or coronary artery disease, which can further weaken the heart?

Different classifications of HF can be treated with varying degrees of efficacy. HFrEF, resulting from weakened cardiac contraction, is more readily treated compared to HFpEF, which results from a reduced ability of the heart to relax and fill with blood, 

and for which no clinical therapy exists.

Further, in-hospital worsening and post-discharge death of acute HF patients 

Multiple clinical trials have been performed to test drug therapies on acute HF patients—yet even those drugs showing positive benefits in moderately-sized phase 2 trials have largely failed to show those same benefits in more extensive phase 3 clinical trials.

 is reinforced by the recent phase 3 trial failure of the drug Serelaxin to replicate the reduction in cardiovascular mortality shown in a phase 2 trial. But why do these trials keep failing?

One reason may be that HF is not an acute phenomenon, though its symptoms may come about acutely. Despite being labeled ‘acute HF’, which defines a sudden episode of worsening HF requiring hospitalization, McCullough (2017) and Parker (2019) suggest it is probable that long-term, underlying cardiovascular damage results in symptomatic HF once a tipping point is reached, and that this damage is not reversed effectively during 48-hour therapy.

In addition, treating HF symptoms without treating the underlying causes will not be an effective long-term therapy.

What is to be done and why is more not being done in the prevention and treatment of HF? Is it enough to divert more funding to understand the differences between HF classifications, and the best treatment options for each? Or should we place more emphasis on the physician and individual to become educated about the best ways to prevent HF development or progression?

While the answer may lie somewhere in the middle, Parker concluded that, “A focus on intensive out patientcare (rather than an obsession with inpatient therapy) is needed to reduce the burden of heart failure.”

Metra (2017) summarized: “Disease-management programs must provide adequate education for the patient and their family, home support (particularly in the post-discharge phase), assessment of adherence to treatment, dietary advice, early detection of signs of decompensation, and readily available access to healthcare services.”

Metra added that, in the context of increasing disease burden and continued high morbidity and mortality, new acute HF and HFpEF therapies are “desperately needed.”

Future articles in this series will discuss differences in HF classification, progression and comorbidities, while further articles will discuss the failure of HF clinical trials, education-based approaches to prevent HF occurrence, and steps to enact more efficient development of HF drug therapies.

Far and away, cardiovascular disease is the greatest killer of people in the US. At the crux of it is heart failure, an often misunderstood condition in need of improved options.

Brian Martin, PhD

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