The Struggle Towards a Universal Definition of Heart Failure—How to Proceed?

Johann Bauersachs


Eur Heart J. 2021;42(24):2331-2343. 

Definitions and classifications are crucial in medicine and provide the basis for proper and timely diagnosis to enable prompt, precise, and efficient therapies. The diagnosis of heart failure (HF) currently relies on signs (pulmonary crackles, peripheral oedema) and symptoms (dyspnoea on exertion, fatigue) that are not always objective, and neither sensitive nor specific.[1,2] Many patients are not diagnosed with HF before they get hospitalized for a decompensation. Although there are several evidence-based treatments for HF with reduced ejection fraction (HFrEF) and even for asymptomatic left ventricular (LV) dysfunction (ejection fraction <40%), the diagnosis is often made late, and valuable time has passed before effective treatments are initiated. Even in patients with symptoms, frequently it takes many months or even years until the diagnosis is made. Especially HF without significant reduction in LV ejection fraction may be mistaken even by cardiologists.

Against this background, the current debate articles, one of the first of this newly introduced format in the European Heart Journal, appraise the value of a universal definition of HF based on the determination of circulating natriuretic peptide (NP) levels.[3] The enormous theoretical advantage of NPs as central diagnostic markers for HF is that they would allow an objective diagnostic standard and that NPs are generally elevated before symptoms or signs of HF develop. Production of NPs—exclusively synthesized in myocardial tissue—depends on intra-cardiac volumes and filling pressures, which determine wall stress. Increased NP levels do not only reflect LV systolic function but may be secondary to other cardiac abnormalities such as diastolic dysfunction, valvular heart disease, right HF or atrial fibrillation.[3] Nevertheless, almost all of these culminate in elevations of plasma volume and dilatation of the left atrium, early events in HF development that precede clinical signs/symptoms. Thus, it is tempting to use NPs instead of non-specific signs/symptoms to set a new universal definition of HF. Despite concerns about sensitivity and specificity in some patients, NPs are already a crucial component for the diagnosis or exclusion of both acute HF and HF with preserved ejection fraction (HFpEF).[2,4] Given the difficulties in diagnosing and treating HFpEF, the endeavours of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) to better define this complex entity have led to the definition of a new subcategory of HFpEF in the 2016 ESC guidelines, i.e. HF with mid-range ejection fraction (HFmrEF), the diagnosis of which requires an ejection fraction of 40–49%, elevated NP levels and either relevant structural heart disease or diastolic dysfunction on echocardiography.[2] Albeit criticized by some, the introduction of this new subcategory has stimulated considerable research efforts, e.g. showing that neurohormonal modulators such as beta-blockers, candesartan, and spironolactone, are almost equally effective in reducing hard clinical outcomes in HFmrEF compared to HFrEF, which prompted respective HFA recommendations for the treatment of HFmrEF.[5,6] This example reiterates the importance of setting better definitions for complex diseases to stimulate research and pave the way to better diagnosis, treatment, and ultimately patient outcomes.

The concept for a universal definition of HF proposed by Cleland et al. provides an excellent basis for the current efforts of different HF societies and associations, including the HFA of the ESC, to develop a universal definition of HF that is accepted worldwide with the goal of improving diagnosis and treatment of (early stages of) HF globally. The authors compare their suggestion with the universal definition of myocardial infarction based on troponin levels. While troponins clearly have revolutionized diagnostic and treatment strategies for acute coronary syndromes (ACS), in most cases HF is undoubtedly a chronic disease with subtle onset lacking the acute symptom of chest pain that triggers troponin determination in suspected ACS. However, also in ACS, it took decades until the current 1-h rule-in/rule-out algorithm using high-sensitivity troponin was firmly established.[7] In their counterstatement, Pfeffer and Teerlink point out several important caveats precluding the simple introduction of NP elevation for HF diagnosis. More evidence is necessary before NPs can be used as the central diagnostic tool for HF in the broad, mostly asymptomatic population. These two excellent articles will clearly stimulate further discussion regarding a universal definition of HF that hopefully will lead to improved patient outcomes.