The 4A  classification for prognostic stratification of patients with tricuspid regurgitation. A multicenter study

Tricuspid regurgitation (TR) is a prevalent valve disease associated with increased morbidity and mortality. Identifying symptomatic patients can be challenging, as early symptoms are often insidious. The 4A classification, based on the presence of Asthenia, Ankle swelling, Abdominal pain/distention, and Anorexia, was recently proposed as a clinical tool for TR patients. 4A classification ranges from A0 (no A) to A3 (three or four A's present). This study aimed to validate the prognostic impact of the 4A classification in a multicentric cohort of patients with significant TR.

We included 640 consecutive patients with at least moderate TR diagnosed by echocardiography from nine hospitals. Baseline functional status was assessed using NYHA classification and the 4A classification. Clinical outcomes, including hospitalization due to heart failure (HF) and cardiovascular mortality, were recorded.

During a mean follow-up of 20.6 ± 16.0 months, 122 patients (19 %) reached the combined endpoint (101 HF admissions and 21 cardiovascular deaths). Higher 4A classification (A2 or A3) was significantly associated with increased adverse events. In multivariate analysis, after exclusion of patients with left valve disease ≥ moderate, pre-capillary pulmonary hypertension patients and those with TR in the context of RV disease, only the 4A classification, A2 (HR 8.91), A3 (HR 9.20) and the presence of chronic kidney disease (HR 2.10) were independent markers of HF and cardiovascular mortality.

The 4A classification is a simple yet powerful clinical tool for risk stratification in patients with significant TR. This study validates its prognostic utility in a multicenter cohort, highlighting its role in identifying patients at higher risk of adverse outcomes, particularly when TR is the predominant valve disease and NYHA classification may not fully capture the burden of the disease.