Heart Failure Inflammation: Can Targeted Treatment Help?

How Common Is Inflammation in Heart Failure?

Inflammation is attracting attention as a possible contributor to the continuing burden of heart failure. An analysis published in JACC: Heart Failure examined participants from SELECT, SOUL and FLOW. Elevated high-sensitivity C-reactive protein, or hsCRP, occurred in 52.5% of participants with preserved or mildly reduced ejection fraction and 49.4% with reduced ejection fraction. Ejection fraction measures the proportion of blood the left ventricle pumps out with each contraction. [Published analysis](https://pubmed.ncbi.nlm.nih.gov/41099689/).

Higher hsCRP was associated with obesity, diabetes and poorer kidney function. These associations cannot establish whether inflammation caused worsening heart failure or whether suppressing it would help. Participants came from selected trial populations, limiting how confidently the percentages can be applied to every person with heart failure. [Study findings and limitations](https://pubmed.ncbi.nlm.nih.gov/41099689/).

Why Does Lowering Inflammation Not Always Improve Heart Failure?

CRP is produced by the liver in response to inflammation. Its concentration can rise because of infection, inflammatory disease and other conditions, so a high result cannot identify where inflammation is occurring or what caused it. The high-sensitivity test detects smaller increases in the same protein. For an individual patient, clinicians interpret the result alongside symptoms, medical history and other investigations. [MedlinePlus explanation of CRP testing](https://medlineplus.gov/lab-tests/c-reactive-protein-crp-test/).

The ATTACH trial illustrates why biological plausibility needs clinical testing. Published in Circulation in 2003, it evaluated infliximab, which blocks the inflammatory messenger tumor necrosis factor, in 150 people with moderate-to-severe heart failure. Treatment suppressed inflammatory markers but did not improve the trial's primary measure of clinical status. The higher-dose group experienced an increased combined risk of death or hospitalization for heart failure. [ATTACH randomized trial](https://pubmed.ncbi.nlm.nih.gov/12796126/).

This result applies to the treatment, doses and population studied; it does not establish that every approach to inflammation will fail. Its practical implication is that researchers must demonstrate meaningful patient benefits and acceptable safety. Improvements in symptoms, physical function, hospitalization rates and survival provide the evidence needed to judge a proposed treatment.

What Can Patients With Heart Failure Do Now?

For heart failure with reduced ejection fraction, guideline-directed treatment includes four foundational medicine classes: a renin-angiotensin system medicine, preferably an angiotensin receptor-neprilysin inhibitor when appropriate; an evidence-based beta-blocker; a mineralocorticoid receptor antagonist; and an SGLT2 inhibitor. Selection and dosing depend on factors including blood pressure, kidney function and potassium. Treatment recommendations differ for preserved ejection fraction, making an accurate diagnosis essential. [AHA/ACC/HFSA heart failure guideline](https://www.ahajournals.org/doi/abs/10.1161/cir.0000000000001063).

Over-the-counter anti-inflammatory painkillers are not a treatment for inflammatory risk in heart failure. Nonsteroidal anti-inflammatory drugs, including ibuprofen and naproxen, can promote sodium and water retention and worsen heart failure. Patients should check pain-relief choices with their clinician or pharmacist. The guideline specifically recommends avoiding or withdrawing NSAIDs whenever possible in reduced-ejection-fraction heart failure. [Guideline recommendations on potentially harmful medicines](https://www.heart.org/-/media/832EA0F4E73948848612F228F7FA2D35.pdf).

A medication review should also include supplements and herbal products. The American Heart Association advises patients to understand the purpose and schedule of each medicine and to discuss changes with their care team. A laboratory result is a reason for an informed review, rather than an instruction to change treatment independently. [American Heart Association medication guidance](https://www.heart.org/en/health-topics/heart-failure/treatment-options-for-heart-failure/medications-used-to-treat-heart-failure).