Effect of IL-1 Blockade With Anakinra on Heart Failure Outcomes in Patients With Anterior Versus Nonanterior ST Elevation Myocardial Infarction

Buono, Marco Giuseppe Del; Damonte, Juan Ignacio; Chiabrando, Juan Guido; Markley, Roshanak; Turlington, Jeremy; Trankle, Cory R.; Kang, Le; Biondi‐Zoccai, Giuseppe; Tassell, Benjamín W. Van; Abbate, Antonio

doi:10.1097/fjc.0000000000001240

Cited by 7 publications

(5 citation statements)

References 31 publications

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“…Treatment with anakinra prevented new heart failure events in experimental and randomized clinical trials ( 31 ). Since the outcome of infection in the constitutive absence of IL-1R reflect the role of IL-1β in the generation of CCC, which based on our results, seems to be of little relevance, we performed IL-1R blockade in infected WT mice.…”

Section: Resultsmentioning

confidence: 99%

“…Treatment with anakinra prevented new heart failure events in experimental and randomized clinical trials (31). Since the Though treatment with anakinra did not significantly alter survival (Figure 4A), weight gain (Figure 4B), or IL-1b plasma levels (Figure 4C) during the chronic stage, there was a visual clinical improvement, with less pronounced disease signals such as prostration, bald spots, ruffled fur, and hunched back (Figure 4D).…”

Section: Treatment With Anakinra Does Not Interfere Much With Ventric...mentioning

confidence: 98%

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IL-1β is not critical to chronic heart dysfunction in mice with Chagas disease

et al. 2022

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Long after Trypanosoma cruzi infection, 40% of individuals develop a progressive chronic chagasic cardiomyopathy (CCC), with systolic dysfunction and arrhythmias. Since we previously showed IL-1β mediates the development of systolic dysfunction and cardiac arrhythmias in diabetes mellitus and cardiorenal syndrome, and IL-1β remains elevated in Chagas disease patients, here we tested the role of IL-1β in CCC using a mouse model. Mice deficient in IL-1R expression (Il-1r−/−) survived acute T. cruzi infection with greater parasitemia than controls but did not lose weight as wild-type (WT) did. At the chronic stage, WT presented prolonged ventricular repolarization intervals (QJ), while Il-1r−/− presented intervals like noninfected controls. Infected Il-1r−/− and WT did not differ in stroke volume (SV), the incidence of cardiac arrhythmias on electrocardiography (EKG), whole heart action potential duration (APD), or the incidence of triggered activity after S1–S2 protocol, which is a measure of susceptibility to cardiac arrhythmias. We also treated chronically infected WT mice with an IL-1R antagonist, anakinra. Treatment shortened the QJ interval but did not improve the SV or the incidence of cardiac arrhythmias on EKG. Anakinra failed to reduce triggered activity following the electrical extra-stimulation protocol. In conclusion, the absence of functional IL-1β/IL-1R signaling did not prevent or reverse the decrease of SV or the incidence of cardiac arrhythmias induced by chronic T. cruzi infection, implying this is not a critical mechanism in generating or maintaining CCC. Since similar cardiac abnormalities were previously credited to IL-1β signaling, ruling out this mechanism is important to discourage further attempts of IL-1β blockade as a therapeutical measure.

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Section: Resultsmentioning

confidence: 99%

Section: Treatment With Anakinra Does Not Interfere Much With Ventric...mentioning

confidence: 98%

IL-1β is not critical to chronic heart dysfunction in mice with Chagas disease

et al. 2022

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“…Perhaps the clearest demonstration of the barriers between inflammatory disease-specific efficacy and broader application is with TNF-α antagonists: whereas observational studies of RA patients suggested a benefit of TNF-α antagonists in reducing rates of HF hospitalization [144], this HF-reducing benefit was not replicated when TNF-α antagonists were tested in the general HF population without RA [145,146]. Perhaps more promising are the results of a sub-analysis of the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS), in which treatment of post-MI patients with canakinumab, an IL-1β antagonist, led to a dose-dependent reduction in HF hospitalization and a composite of HF hospitalization and mortality [147 A separate, smaller trial of IL-1 receptor antagonist anakinra in post-MI patients likewise yielded a reduction in incident HF [148]. Effects of colchicine on HF are less clear, as randomized trials have focused largely on post-MI recurrence of athero-thrombotic CVD rather than HF and variably suggested benefit [149] or neutrality/possible harm [150].…”

Section: Leveraging Insights From Chronic Inflammatory and Infectious...mentioning

confidence: 99%

Heart Failure in Chronic Infectious and Inflammatory Conditions: Mechanistic Insights from Clinical Heterogeneity

Beydoun

Feinstein

2022

Curr Heart Fail Rep

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Purpose of ReviewThe balance between inflammation and its resolution plays an important and increasingly appreciated role in heart failure (HF) pathogenesis. In humans, different chronic inflammatory conditions and immune-inflammatory responses to infection can lead to diverse HF manifestations. Reviewing the phenotypic and mechanistic diversity of these HF presentations offers useful clinical and scientific insights. Recent Findings HF risk is increased in patients with chronic inflammatory and autoimmune disorders and relates to disease severity. Inflammatory condition-specific HF manifestations exist and underlying pathophysiologic causes may differ across conditions. Summary Although inflammatory disease-specific presentations of HF differ, chronic excess in inflammation and autoinflammation relative to resolution of this inflammation is a common underlying contributor to HF. Further studies are needed to phenotypically refine inflammatory condition-specific HF pathophysiologies and prognoses, as well as potential targets for intervention.

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“…We recently described that in patients with ST-segment elevation myocardial infarction (STEMI), anakinra leads to a significant reduction in leukocyte count with a relative reduction in neutrophils and an increase in eosinophils [ 7 ]. In patients with STEMI, anakinra was also associated with a reduction in HF-related events [ 8 , 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Change in Eosinophil Count in Patients with Heart Failure Treated with Anakinra

Golino

Moroni

Buono

et al. 2023

Cells

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Background: Interleukin-1 blockade with anakinra leads to a transient increase in eosinophil blood count (eosinophils) in patients with acute myocardial infarction. We aimed to investigate the effect of anakinra on changes in eosinophils in patients with heart failure (HF) and their correlation with cardiorespiratory fitness (CRF). Methods: We measured eosinophils in 64 patients with HF (50% females), 55 (51–63) years of age, before and after treatment, and, in a subset of 41 patients, also after treatment cessation. We also evaluated CRF, measuring peak oxygen consumption (VO2) with a treadmill test. Results: Treatment with anakinra significantly and transiently increased eosinophils, from 0.2 [0.1–0.3] to 0.3 [0.1–0.4] × 103 cells/µL (p < 0.001) and from 0.3 [0.2–0.5] to 0.2 [0.1–0.3] × 103 cells/µL, with suspension (p < 0.001). Changes in eosinophils correlated with the changes in peak VO2 (Spearman’s Rho = +0.228, p = 0.020). Eosinophils were higher in patients with injection site reactions (ISR) (n = 8, 13%; 0.5 [0.4–0.6] vs. 0.2 [0.1–0.4] × 103 cells/µL, p = 0.023), who also showed a greater increase in peak VO2 (3.0 [0.9–4.3] vs. 0.3 [−0.6–1.8] mLO2·kg−1·min−1, p = 0.015). Conclusion: Patients with HF treated with anakinra experience a transient increase in eosinophils, which is associated with ISR and a greater improvement in peak VO2.

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Effect of IL-1 Blockade With Anakinra on Heart Failure Outcomes in Patients With Anterior Versus Nonanterior ST Elevation Myocardial Infarction

Cited by 7 publications

References 31 publications

IL-1β is not critical to chronic heart dysfunction in mice with Chagas disease

IL-1β is not critical to chronic heart dysfunction in mice with Chagas disease

Heart Failure in Chronic Infectious and Inflammatory Conditions: Mechanistic Insights from Clinical Heterogeneity

Change in Eosinophil Count in Patients with Heart Failure Treated with Anakinra

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