ACC/AHA heart failure staging

Clinical background

Heart failure develops along a continuum from exposure to risk factors, through asymptomatic structural heart disease, to symptomatic and finally refractory failure. The decision the tool serves is where on this continuum a patient lies, since this determines which preventive and therapeutic measures are indicated. Without a structured classification, the clinician tends to focus on patients with already manifest failure and to overlook the large group with risk factors or preclinical heart disease in whom progression can be delayed or prevented.

The ACC/AHA staging was introduced in 2001 and revised in the 2013 and 2022 guidelines. The most recent revision added raised biomarkers (natriuretic peptides and troponins) as a criterion for stage B and changed the terminology to "at risk" (stage A) and "pre-HF" (stage B) [1].

Applying the ACC/AHA staging of heart failure

The classification is hierarchical and unidirectional. The highest applicable stage is assigned according to the following algorithm:

$$\text{Stage} = \begin{cases} A & \text{if risk factors are present, but no structural abnormality and no symptoms} \ B & \text{if structural heart disease, a reduced EF or raised biomarkers/filling pressures are present, without symptoms} \ C & \text{if current or previous symptoms/signs of heart failure are present} \ D & \text{if advanced/refractory heart failure requiring specialised measures is present} \end{cases}$$

Risk factors for heart failure include hypertension, diabetes, coronary artery disease, obesity, exposure to cardiotoxic agents and a family history of cardiomyopathy. A structural/functional abnormality in stage B includes a reduced ejection fraction (EF <50%), left ventricular hypertrophy, atrial enlargement, raised filling pressures or raised natriuretic peptides (BNP $\geq$ 35 ng/L, NT-proBNP $\geq$ 125 ng/L) or a high-sensitivity troponin above the 99th percentile [2]. Stage C requires current or previous symptoms or signs of heart failure. Stage D is defined by refractory failure requiring inotropes, mechanical circulatory support, transplantation or palliative care [1].

The evidence base is not a single cohort study but a consensus-based guideline. The 2022 guideline summarised evidence from a systematic literature search in MEDLINE, EMBASE, Cochrane and other databases, covering May 2020 to December 2020 with a supplementary search up to September 2021 [1]. The staging system itself was originally derived in the 2001 guideline and has since been updated iteratively on the basis of accumulating evidence about biomarkers and imaging findings.

Interpretation in practice

The stage determines the treatment goal and the level of care. Since the stages are cumulative and unidirectional, a patient who has at any time had symptoms always remains at least stage C, even if she is later compensated and becomes asymptomatic.

Validation and performance

Unlike a scoring scale with a continuous risk calculation, the staging system has no traditional measures such as a c-statistic or calibration in a derivation cohort. Its performance has instead been evaluated in population-based cohorts by studying how well the stages discriminate future risk.

The most comprehensive external evaluation was carried out by Mohebi et al., who analysed 11,618 participants from three longitudinal cohorts (MESA, CHS and the Framingham Heart Study) [2]. Using the 2022 criteria, 16.7% were classified as healthy, 37.4% as stage A, 43.2% as stage B and 2.7% as stage C/D. Compared with the 2013 criteria, the 2022 definition produced a substantial shift from stage A to stage B, from 15.9% to 43.2%, driven by the addition of raised natriuretic peptides and troponins as criteria for stage B.

Despite this shift, the relative risk of progression to symptomatic heart failure for stage B was maintained: HR 10.61 (95% CI 9.00 to 12.51) compared with healthy individuals [2]. The incidence of heart failure, cardiovascular death and all-cause mortality rose stepwise across the stages with both classification systems. The most important difference was that the 2022 criteria identified a considerably larger proportion of women and of Hispanic and Black individuals as stage B, which partly reflects higher biomarker levels in these groups.

In a German cohort (n = 2,496) from three studies within the Competence Network Heart Failure, patients were distributed across the stages with an increasing prevalence of chronic kidney disease and anaemia from stage A to D [5]. At five-year follow-up, all-cause mortality was associated with both kidney disease (HR 2.1) and anaemia (HR 1.7), with an additive effect when both were present (HR 3.6), independently of stage.

Limitations

The staging system is unidirectional: a patient who has at any time had symptoms remains at least stage C even when fully compensated. This is a design principle, not a flaw, but it means that the stage does not reflect the current symptom burden and cannot be used to monitor the response to treatment. The NYHA classification or patient-reported measures are needed for that purpose.

The biomarker criteria for stage B (BNP $\geq$ 35 ng/L, NT-proBNP $\geq$ 125 ng/L) are taken from diagnostic thresholds for heart failure and have not been validated as screening cut-offs in the general population. The Mohebi study showed that including biomarkers almost tripled the proportion of stage B patients, from 15.9% to 43.2% [2]. It is unclear whether all those now classified as stage B carry a level of risk that warrants specific pharmacological intervention beyond risk factor treatment, particularly those who meet the biomarker criterion alone without a structural abnormality.

The system applies to adult patients and is not validated for children with congenital heart disease. It does not take account of the mechanism of the heart failure (for example valvular disease, hypertrophic cardiomyopathy, amyloidosis), which can affect both the rate of progression and the choice of treatment independently of stage. Patients with valve-mediated heart failure may pass through the stages more rapidly and require specific valve intervention, which the system does not capture.

SGLT2 inhibitors, which now have demonstrated efficacy in delaying progression from stage A to B in patients with diabetes, were added as a recommendation in the 2022 guideline, but the treatment algorithm attached to the stages has not been updated in proportion to this evidence [4].

References

1. Heidenreich PA, Bozkurt B, Aguilar D et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. Circulation 2022. PMID: 35363499
2. Mohebi R, Wang D, Lau ES et al. Effect of 2022 ACC/AHA/HFSA Criteria on Stages of Heart Failure in a Pooled Community Cohort. J Am Coll Cardiol 2023. PMID: 37286252
3. Danelich IM, Reed BN, Sueta CA. Stage A: Can Heart Failure Be Prevented? Curr Cardiol Rev 2015. PMID: 24251457
4. Patel R, Peesay T, Krishnan V et al. Prioritizing the Primary Prevention of Heart Failure: Measuring, Modifying and Monitoring Risk. Prog Cardiovasc Dis 2024. PMID: 38272339
5. Gerhardt LMS, Kordsmeyer M, Sehner S et al. Prevalence and prognostic impact of chronic kidney disease and anaemia across ACC/AHA precursor and symptomatic heart failure stages. Clin Res Cardiol 2023. PMID: 35648270