Inflammatory Mechanisms in Heart Failure
Summary
Heart failure is increasingly recognised as a syndrome driven not only by haemodynamic stress and neurohormonal dysregulation but also by chronic inflammation. In the injured myocardium, dead or stressed cells release damage-associated molecular patterns that activate resident immune cells and recruit circulating leukocytes. This sterile inflammation is characterised by an early neutrophilic response followed by monocyte-derived macrophages that can either promote repair or perpetuate injury through pro-inflammatory cytokine release. Meanwhile, systemic comorbidities such as obesity, diabetes and chronic kidney disease generate a low-grade inflammatory milieu that exacerbates cardiac dysfunction. In heart failure with reduced ejection fraction, pro-inflammatory mediators impair contractility and promote adverse remodelling, whereas in heart failure with preserved ejection fraction, microvascular inflammation and endothelial dysfunction drive diastolic impairment and myocardial stiffness. Key cytokines including tumour necrosis factor-α, interleukins-1 and ‑6 and C-reactive protein serve both as biomarkers and potential therapeutic targets. Despite promising preclinical data, clinical trials of broad anti-cytokine strategies have yielded mixed results, prompting a shift towards precision medicine approaches that aim to characterise individual immune profiles and harness resolution pathways to restore cardiac homeostasis.
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Inflammatory Mechanisms in Heart Failure publication trend
The graph below shows the total number of articles in inflammatory mechanisms in heart failure across all publications each year (not limited to Nature Index journals).
Technical terms
Cytokine: Small protein released by immune cells that modulates inflammation and cell signalling.
Damage-associated molecular pattern (DAMP): Endogenous molecules released by stressed or dying cells that trigger sterile inflammation.
HFpEF (Heart failure with preserved ejection fraction): Syndrome of heart failure characterised by normal systolic function and impaired diastolic filling.
HFrEF (Heart failure with reduced ejection fraction): Syndrome of heart failure defined by impaired systolic contraction and reduced ejection fraction.
Resolution pathways: Endogenous mechanisms that actively terminate inflammation and promote tissue repair.
References
- Adverse Outcomes Associated With Interleukin-6 in Patients Recently Hospitalized for Heart Failure With Preserved Ejection Fraction. Circulation Heart Failure (2023).
- Inflammation in Human Heart Failure: Major Mediators and Therapeutic Targets. Frontiers in Physiology (2021).
- Metabolism and Chronic Inflammation: The Links Between Chronic Heart Failure and Comorbidities. Frontiers in Cardiovascular Medicine (2021).
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