۲- Methods

۳- Results

۴- Discussion

۵- Conclusions

References

Introduction

Heart failure (HF) is becoming a tremendous burden on healthcare systems worldwide. Functional capacity is a crucial parameter correlated with outcomes [1–۴]. Currently, the gold standard for assessing the functional state is the cardiopulmonary gas exchange exercise test (CPET) [5, 6]. Because it requires instruments and is inconvenient to administer because it is time-consuming, the New York Heart Association functional classification (NYHA Fc) is widely used instead [7]. However, previous studies found that interobserver reproducibility of NYHA Fc when assessing class II and class III was only 56%, a result little better than chance [4]. A more precise assessment tool is needed. Functional assessment estimates the severity of imbalance between cardiac supply and whole body demand, which can represent the entire body’s metabolic status. Previously, we and others demonstrated that patients’ plasma-based metabolic profile provided valuable information about HFrelated metabolic disturbance [8–۱۰], diagnosis [11–۱۳], and prognosis [11, 14, 15]. We subsequently simplified the metabolomics assessment into an amino acid-based profile that includes histidine, ornithine, and phenylalanine (HOP score) [16, 17]. We found that the HOP score was wellcorrelated with functional capacity, as estimated by a sixminute walking distance. Although NYHA functional classes III and IV suggest poor outcomes, the largest group of outpatients is usually in the NYHA class II category, which is often overlooked by clinicians. However, results of recent clinical trials strongly recommend active intervention for all patients from classes II to IV [1, 2]. In this study, we would like to use CPET to investigate whether HOP scores could be an objective substitute for identifying HF outpatients in the functional class ≥ II. We also would like to see whether the HOPdefined worse functional classification represents higher risk of HF-related rehospitalization/death in 12 months among HF patients with reduced ejection fraction (HFrEF), mid-range EF (HFmrEF), and preserved EF (HFpEF) [18].