Author + information
- Luca Baldetti, MD∗ (, )
- Guglielmo Gallone, MD,
- Francesco Melillo, MD,
- Matteo Pagnesi, MD and
- Alessandro Beneduce, MD
- ↵∗San Raffaele Hospital, Via Olgettina 60, Milan, 20132, Italy
We read with great interest the work by Pascual-Figal et al. (1). Findings of this study add perspective to the “inflammatory hypothesis,” furnishing rationale for a new treatment target in the strive to treat heart failure (HF) successfully.
This study once again reinforces the central role of interleukin (IL)-1β in cardiovascular diseases by linking its circulating concentrations to 1-year outcome in patients with HF.
Surprisingly, ischemic HF etiology (despite being commonly encountered in clinical settings) was relatively underrepresented (33%), as was the prevalence of previous myocardial infarction (MI; 24%). Pascual-Figal et al. (1) did not address whether an interaction between HF etiology and study findings was present. Although this may somewhat limit extrapolation of these results to general HF patients, it also shapes 2 conceptual interpretative frameworks for the study findings. Could IL-1β levels have been markers of nonischemic inflammatory cardiomyopathy disease activity in these patients? In such cases, higher cytokine levels could likely represent ongoing inflammation leading to myocardial damage (as reinforced by the association of IL-1β levels with troponin and N-terminal pro–B-type natriuretic peptide concentrations in this study). Beyond clinical relevance, given that higher levels of both IL-1β and NLRP3 portend worse prognosis in patients with nonischemic dilated cardiomyopathy (2), this finding may suggest profound pathophysiologic implications for this HF subset.
Conversely, could inclusion of a greater proportion of patients with coronary artery disease and, especially, post-MI patients have been able to show an even stronger association between IL-1β levels and patient prognosis? Inflammatory residual risk is common among such conditions, as hinted at by the nominally higher coronary artery disease prevalence in the higher IL-1β quartiles. In addition, reduction of the inflammatory burden by targeting IL-1β early after MI and in the chronic setting reduces infarct size and prevents subsequent HF in preclinical experiments, thereby reinforcing inflammation as a prognosis diver (3). From bench to bedside, canakinumab reduced HF-related events in post-MI CANTOS (Canakinumab Antiinflammatory Thrombosis Outcome Study) (4) patients.
Inflammation and IL-1β are promising therapeutic targets in both scenarios. Better characterization of the relationship between causative HF etiology and inflammatory activity is warranted and may add insight into this interesting study.
In conclusion, this work adds robustness to the HF-inflammation association and, hopefully, may prompt further research addressing inflammation across the whole clinical spectrum of HF, encompassing acute decompensated HF, chronic stable HF, and post-MI HF prevention.
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2019 American College of Cardiology Foundation
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