Heart Failure Classification in Clinical Practice: Time to Redefine?
Heart failure (HF) represents one of the major disease burdens worldwide, with congestive HF-related Medicare expenditures remaining high and posing a global challenge. Despite modern therapeutic strategies, patients with HF face significantly increased risks of recurrent hospitalizations, morbidity, and mortality after the initial manifestation of the disease. The complexity of HF necessitates a comprehensive and accurate classification system to improve diagnosis, risk stratification, and treatment outcomes.
Currently, the widely accepted definition of HF is based on the 2016 European Society of Cardiology (ESC) guidelines, which focus on left ventricular functional assessment and symptoms. Patients are classified according to left ventricular ejection fraction (LVEF) into three categories: HF with reduced ejection fraction (HFrEF) for LVEF ≤40%, HF with mid-range ejection fraction (HFmrEF) for LVEF between 41% and 49%, and HF with preserved ejection fraction (HFpEF) for LVEF ≥50%. The New York Heart Association (NYHA) classification further defines the severity of HF symptoms during exercise or at rest, providing additional therapeutic and prognostic insights.
A recent position paper proposed a universal definition and classification of HF, viewing it as a clinical syndrome caused by structural and/or functional cardiac abnormalities, corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. This classification stages HF into four categories: at-risk for HF (Stage A), pre-HF (Stage B), symptomatic HF (Stage C), and advanced HF (Stage D). Additionally, HF patients are grouped based on LVEF, including HFrEF, HFmrEF, HFpEF, and symptomatic HF with improved ejection fraction (HFimpEF), which is defined as a baseline LVEF ≤40% with a ≥10-point increase to a second measurement of LVEF >40%.
Despite these classifications, only HFrEF patients have consistently benefited from guideline-recommended therapies based on randomized controlled trials (RCTs). Recent RCTs have shown mixed results for HFpEF treatments. For instance, the PARAGON-HF trial found that sacubitril/valsartan did not significantly improve the outcome of total HF hospitalizations and cardiovascular death in HFpEF patients with LVEF ≥45%. However, subgroup analyses suggested potential benefits in women and patients with LVEF ≤57%. On the other hand, the EMPEROR-Preserved trial demonstrated significant risk reduction with empagliflozin for the composite of cardiovascular death or hospitalization for HF in adults with HFpEF, marking a breakthrough in HFpEF treatment.
The neutral results of many RCTs in HFpEF may be attributed to the multiple etiologies underlying the condition. Unlike HFrEF, where neurohormonal activation is prevalent, HFpEF patients exhibit diverse pathophysiological mechanisms, making neurohormonal inhibition-oriented medications less effective. This has led to discussions on an alternative etiology-oriented classification for HFpEF, which could guide more targeted therapies.
A proposed etiology-oriented classification divides HFpEF patients into five categories: HFpEF-1 (vascular-related HFpEF), HFpEF-2 (cardiomyopathy-related HFpEF), HFpEF-3 (right heart and pulmonary-related HFpEF), HFpEF-4 (valvular- and rhythm-related HFpEF), and HFpEF-5 (extracardiac disease-related HFpEF). This classification hypothesizes that HFpEF patients may particularly benefit from therapies tailored to their underlying disease, encouraging clinical studies to validate this approach.
To further enhance HF management, an extended etiology-oriented classification could be applied to the entire HF spectrum, combining LVEF, etiology, and symptom aspects into a multifaceted system. The proposed Etiology-Systolic function-NYHA classification Heart Failure (ESN-HF) coding system defines HF patients based on etiology (I–V), LVEF (A–D), and NYHA classification (1–4). This system aims to cover the entire spectrum of HF, including HFimpEF, which accounts for patients with improved LVEF during the disease course.
In summary, HF is an extremely complex systemic syndrome that is not yet fully reflected in current clinical definitions. The adoption of a superordinate multifaceted classification system could greatly improve diagnostic accuracy, simplify patient risk stratification, and enhance etiology- and stage-oriented therapeutic decision-making. Future studies are encouraged to validate the utility of this approach in improving HF patient care.
doi.org/10.1097/CM9.0000000000001823
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