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Arterio-venous gradient of active interleukin-18 is associated with diastolic dysfunction: a cross-sectional study
Hirofumi Makino1, Yu Yasuda2, Yusuke Morita2
1Internal Medicine 1, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan.
Insights
Local interleukin-18 (IL-18) gradients are associated with diastolic dysfunction in heart failure patients. Higher arterio-venous ratios of active IL-18 correlate with impaired myocardial relaxation, especially in those with elevated filling pressures.
Area of Science:
- Cardiology
- Immunology
- Biochemistry
Background:
- Diastolic dysfunction is a major factor in heart failure (HF) symptoms and prognosis.
- Interleukin-18 (IL-18) and IL-6 are key inflammatory cytokines in HF, but their local roles are unclear.
- This study explores the link between arterio-venous (A/V) cytokine gradients and diastolic dysfunction.
Purpose of the Study:
- To investigate the association between A/V gradients of active IL-18 (aIL-18) and active IL-6 (aIL-6) and diastolic dysfunction.
- To evaluate the relationship between these cytokine gradients and echocardiographic and clinical parameters of diastolic dysfunction.
- To assess the in vitro effects of aIL-18 on cardiac fibroblasts.
Main Methods:
- Eighty-seven heart failure patients undergoing cardiac catheterization were enrolled.
- Paired arterial and venous blood samples were analyzed for aIL-18 and aIL-6 concentrations.
- Associations with echocardiographic measures (e.g., E/e'), clinical scores (HFA-PEFF), and in vitro fibroblast responses were evaluated.
Main Results:
- The cohort had impaired myocardial relaxation with preserved ejection fraction.
- The aIL-18 A/V ratio correlated with markers of diastolic dysfunction, including average E/e', tricuspid regurgitation pressure gradient, and HFA-PEFF score.
- These correlations were stronger in non-diabetic patients and those with elevated LV filling pressure; aIL-18 stimulated fibroblast proliferation and collagen synthesis in vitro.
Conclusions:
- Local IL-18 gradients, indicated by the aIL-18 A/V ratio, are associated with diastolic dysfunction in heart failure.
- The findings suggest a role for local IL-18 in diastolic dysfunction, particularly in patients with increased filling pressures.
- Further research is warranted to confirm these exploratory findings and elucidate the mechanisms involved.
Introduction:
Diastolic dysfunction is a key determinant of symptoms and prognosis in heart failure (HF). Interleukin (IL)-18 and IL-6 are key inflammatory cytokines in HF; however, their local activation within the cardiopulmonary circulation and relevance to diastolic dysfunction remain unclear. This exploratory study investigated associations between arterio-venous (A/V) cytokine gradients and diastolic dysfunction.
Methods:
Eighty-seven patients undergoing diagnostic cardiac catheterization were enrolled. Paired arterial samples from the left ventricle (LV) or ascending aorta and peripheral venous samples were obtained simultaneously or within 24 h of the procedure. Active IL-18 (aIL-18) and IL-6 concentrations were measured, and associations with echocardiographic and clinical parameters were evaluated. Active interleukin-18-induced fibrotic responses were evaluated in human cardiac fibroblasts.
Results:
The cohort exhibited impaired myocardial relaxation (septal e': 5.3 ± 2.0 cm/s) and preserved ejection fraction (57.4 ±11.8%). The aIL-18 A/V ratio correlated with average E/e' (r = 0.31, P < .01), tricuspid regurgitation pressure gradient (r = 0.29, P = .015), and Heart Failure Association-Pre-test assessment, Echocardiography & natriuretic peptide, Functional testing, Final aetiology (HFA-PEFF) score (r = 0.23, P = .034). Correlations between the aIL-18 A/V ratio and E/e' were more pronounced in non-diabetic patients and in those with elevated LV filling pressure (average E/e' ≥ 15). Interleukin-6 correlated with albuminuria and pulmonary function; however, no synergistic interaction with aIL-18 was observed. In vitro, aIL-18 stimulated fibroblast proliferation and collagen synthesis.
Conclusion:
The aIL-18 A/V ratio correlated with markers of diastolic dysfunction, particularly in patients with increased filling pressure. These exploratory findings indicate an association between local IL-18 gradients and diastolic dysfunction, warranting further investigation.
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