Heart Failure (HF)

Definition and ClassificationTop

Heart failure (HF) is a clinical syndrome caused by abnormal cardiac structure or function resulting in reduced cardiac output or elevated intracardiac pressures at rest or during exercise.

To support a diagnosis of HF, there must be a presence of symptoms (eg, dyspnea, orthopnea, bendopnea, ankle and/or abdominal swelling, fatigue) and/or signs (eg, elevated jugular venous pressure, pulmonary crackles) of pulmonary or systemic congestion.

In addition, these findings must be validated by elevated natriuretic peptide levels or objective evidence of pulmonary or systemic congestion through diagnostic modalities including imaging (eg, chest radiography, elevated filling pressures on echocardiography) or hemodynamic measurements (eg, right heart catheterization) at rest or during exercise.

The stages of HF can be classified as a continuum:

1) At risk of HF (stage A): Patients who are without structural heart disease, elevated biomarker levels, and signs and/or symptoms of HF but have significant risk factors for HF development. This group includes patients with hypertension, coronary artery disease, diabetes mellitus, obesity, family history of cardiomyopathy, and/or known exposure to cardiotoxins.

Importantly, not all patients with risk factors will go on to develop HF, but primary prevention through modifying risk factors may reduce the development of symptomatic HF. These interventions include regular physical activity, maintaining a healthy diet and weight, limiting alcohol intake, and managing existing comorbidities with evidence-based pharmacotherapies that prevent cardiovascular events including HF.

2) Pre-HF (stage B): Patients without previous or current symptoms/signs of HF and with the presence of one of the following: structural heart disease (eg, left ventricular hypertrophy, cardiac chamber enlargement), abnormal cardiac function (eg, reduced ventricular systolic function, increased filling pressures), or elevated levels of cardiac biomarkers (eg, natriuretic peptide levels, cardiac troponins).

3) Symptomatic HF (stage C): Patients with structural heart disease, functional heart abnormality, or both, with previous or current signs/symptoms of HF.

4) Advanced HF (stage D): Patients with HF refractory or intolerant to guideline-directed medical therapy, severe signs/symptoms of HF at rest, recurrent hospitalizations, requiring advanced interventions (including transplant, mechanical circulatory support, or palliative care).

For therapeutic and prognostic purposes, HF is also classified according to left ventricular ejection fraction (LVEF), which is defined as stroke volume (end-diastolic minus end-systolic volume) divided by the end-diastolic volume.

1) HF with reduced ejection fraction (HFrEF) is typically defined as clinical HF with LVEF ≤40%.

2) HF with mildly reduced ejection fraction (HFmrEF): The LVEF threshold for the diagnosis of HFrEF and heart failure with preserved ejection fraction (HFpEF) has varied across clinical trials and clinical practice guidelines. LVEF between 41% and 49% is considered to be in the gray zone, referred to as mildly reduced ejection fraction.

3) HFpEF is typically defined as clinical HF with LVEF ≥50%.

4) HF with improved ejection fraction (HFimpEF) is typically defined as HF with an LVEF baseline of ≤40%, followed by a ≥10-point increase from baseline, and a subsequent measurement of LVEF >40%.

Clinically, HF may also be classified as left ventricular, right ventricular, or biventricular failure, depending on whether the predominant symptoms of congestion are pulmonary, systemic, or both.

High-output HF refers to clinical HF occurring due to increased cardiac output and hyperdynamic states, which may not always be associated with an underlying structural heart disease.