Abstract
BackgroundInflammation is one of the principal triggering mechanisms for left ventricular fibrosis and remodeling in heart failure, leading to adverse clinical outcomes. Soluble suppression of tumorigenicity 2 (sST2), a member of the interleukin-1 receptor family, is assumed to play a significant role in the fibrotic response to inflammation. Left ventricular mass index (LVMI) is a parameter of the prefibrotic inflammatory phase of heart failure preceding remodeling. The present study aimed to investigate the prognostic value of the sST2/LVMI ratio in heart failure with reduced ejection fraction.MethodsThis was a prospective cohort study. A total of 45 consecutive patients with heart failure with reduced ejection fraction, treated between September 2015 and December 2016, were enrolled. The sST2/LVMI ratio was measured at baseline. The primary endpoint was a composite of cardiovascular mortality and readmission for heart failure. The prognostic impact of the sST2/LVMI ratio was evaluated using a multivariable Cox proportional hazards regression model.ResultsForty-five patients were enrolled in this study. Their average age was 48 ± 14 years, and approximately 20% of them were men. Patients were followed for 9 months, during which the primary outcome occurred in 15 patients. Kaplan–Meier analysis showed that patients with a high sST2/LVMI ratio (≥ 0.39) had shorter event-free survival than those with intermediate (between 0.39 and 0.24) and low ratios (< 0.24) (log-rank, P = 0.022). The fully adjusted multivariable Cox regression analysis showed that the sST2/LVMI ratio was positively associated with the composite outcome in patients with heart failure with reduced ejection fraction after adjusting for confounders (hazard ratio 1.64, 95% confidence interval 1.06 to 2.54). By subgroup analysis, a stronger association was found with age between 40 and 55 years, systolic blood pressure < 115 or ≥ 129 mmHg, diastolic blood pressure < 74 mmHg, hematocrit < 44.5%, and interventricular septum thickness ≥ 8.5 mm.ConclusionIn patients with heart failure with reduced ejection fraction, the relationship between the sST2/LVMI ratio and the composite outcome was linear. A higher baseline ratio of sST2/LVMI was associated with an increased risk of cardiovascular mortality and heart failure rehospitalization in the short-term follow-up.
Highlights
Inflammation is one of the principal triggering mechanisms for left ventricular fibrosis and remodeling in heart failure, leading to adverse clinical outcomes
In the Framingham Heart Study, suppression of tumorigenicity 2 (sST2) was not associated with echocardiographic findings of remodeling [9] and there was no correlation between sST2 levels and cardiac fibrosis, as detected by late gadolinium enhancement on cardiac magnetic resonance imaging (CMRI), in myocarditis patients [10]
The present study demonstrated that the sST2/Left ventricular mass index (LVMI) ratio, which adjusts for the cardiac-remodeling effect of circulating sST2, was positively associated with the composite endpoint of cardiovascular mortality and heart failure (HF) readmission in Chinese patients with HF with reduced ejection fraction (HFrEF)
Summary
Inflammation is one of the principal triggering mechanisms for left ventricular fibrosis and remodeling in heart failure, leading to adverse clinical outcomes. Soluble suppression of tumorigenicity 2 (sST2), a powerful independent predictor of mortality in patients with HF [5], is reported to possess two different functions: antiinflammatory activity [6] and pro-fibrotic activity promoting pathological cardiac remodeling [4, 7] by acting as a nonfunctional decoy IL‐33 receptor. The latter mechanism renders IL-33 unavailable to bind membrane-bound ST2 receptors (ST2L), limiting IL‐33/ST2L signaling [8]. The sST2 level in the circulation was reported to not correlate with cardiac fibrosis in patients with HF [11]
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