Update: Understanding emerging risk factors for heart failure

By Naveed Saleh, MD, MS | Medically reviewed by Yasmine S. Ali, MD, MSCI, FACC, FACP
Published February 6, 2024

Key Takeaways

  • Heart failure continues to be a major cause of morbidity and mortality, with the proportion of cases involving preserved ejection fraction increasing.

  • Emerging risk factors that warrant attention include inflammation, fibrosis, and other factors identified via multiomic analysis.

  • A  better understanding of emerging heart failure risk factors could pave the way for improved management.

A closer look at heart failure indicates a disease of disturbing trends. Although the prevalence of heart failure is increasing, mortality and hospitalization have remained unchanged. Furthermore, the disease is now increasingly shifting toward cases involving heart failure with preserved ejection fraction (HFpEF), for which effective treatment is elusive. HFpEF is an active area of ongoing research, and it is also a disease of substantial disparities, as it disproportionately impacts younger Black populations.

The recognition of emerging risk factors and holistic management of disease burden are important to physicians and their patients. Emerging research may hold the key to more effective management.


Fibrosis and inflammation are causal risk factors in heart failure. They also play a role in post-MI ventricular remodeling, which precedes overt heart failure. 

Inflammation and fibrosis underlie the mechanisms of heart failure with either preserved or reduced ejection fraction. Furthermore, C-reactive protein (CRP), ST2, and galectin are all heart-failure biomarkers being researched.


Multiomics is a type of biological analysis in which multiple “-omes” (ie,  genome, proteome, microbiome, and epigenome) comprise sets of data that may shed more light on heart failure risk factors.

Genetic contributions to HF should reflect precursor manifestations of heart disease such as dilated cardiomyopathy, according to the authors of a review published in Circulation Research.

Genetic testing can identify between 15% and 40% of dilated cardiomyopathy variants depending on whether the disease is familial or sporadic.

Guidelines currently recommend such testing for familial dilated cardiomyopathy.

However, proteomics—the large-scale study of proteins—can further define risk for heart failure. This emerging field offers a link between proteomic signatures and mechanisms of HF including stage, progression, and death. 

Electronic health records

Electronic health records (EHRs) offer longitudinal data sets without rival, and the data can be used for precision phenotyping in heart failure. They can recognize differences in presentations and outcomes, as well as new drug targets.

“Capturing all clinically collected data can enable the identification of previously unrecognized relationships underpinning the HF syndrome and the delineation of mechanistically coherent phenotypes,” according to the authors of the aforementioned review. “The clinical applicability of EHR-based approaches is particularly appealing for risk prediction as EHRs constitute comprehensive repositories of the clinical experience of patients and can integrate a vast amount of complex data that oversubscribed clinicians caring for complex patients could not easily integrate.”

Related: MACE: Clinical implications and recommendations for cardiac care

Machine learning

The elusive nature of HFpEF could be tackled with machine learning, according to FDA, the Centers for Medicare and Medicaid Services, and industry interests. 

Machine learning could result in the discovery of biologically distinct phenotypes and elucidate various responses to treatments. Nevertheless, machine learning requires robust data points, which means the pathophysiologic markers that represent HFpEF need to be adequately represented. 

Advising your patients

The holistic management of heart failure should make prevention an important aspect of care.

Lifestyle interventions such as smoking cessation, healthy eating, weight loss, and management of comorbid cardiovascular conditions are all of cardinal importance.

Statins can help prevent heart attacks and coronary events that lead to heart failure.

Johns Hopkins Medicine offers advice on coping with heart failure that can guide counseling efforts:

  • Patients should monitor symptoms, including swelling of the legs/feet and daily weight measurements to gauge fluid retention. Blood pressure should also be tracked.

  • Patients should receive flu shots and try to avoid contracting respiratory infections that could further decompensate lung function.

  • Encourage patients to remain positive and receive treatment for comorbid depression and anxiety, as well as help with stress management.

  • Patients should feel free to ask questions about work, exercise, and sex, which all vary based on stage of disease.

COVID and heart failure

A special note should be made about patients with heart failure who are hospitalized with COVID-19. Results of a population-based study published in JACC: Heart Failure indicated that about 1 of 4 patients with chronic heart failure who were hospitalized with COVID-19 died. These cases depleted the health care system of resources and variables including advanced age, morbid obesity, and diabetes were related to worse inpatient outcomes. 

“Dedicated and innovative efforts surrounding education and infection control are needed for this high-risk population as the pandemic continues to evolve,” concluded the authors.

What this means for you

Effective treatments for HFpEF remain an area of active research. A better understanding of emerging risk factors could pave the way for improved management. In the interim, patients should be advised on the importance of mitigating risk factors.


  1. Roger VL. Epidemiology of Heart Failure. Circulation Research. 2021;128(10):1421-1434.

  2. Congestive Heart Failure: Prevention, Research and Treatment. Johns Hopkins Medicine.

  3. Bhatt JS. Clinical Outcomes in Patients With Heart Failure Hospitalized With COVID-19. JACC: Heart Failure. 2021;9(1):65-73.

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