The 3S-AF scheme, rather than the 4S-AF scheme, predicts progression in patients with paroxysmal atrial fibrillation: data from RACE V study
Authors: Artola V , Geelhoed B , Van Lande M , Khalilian Ekrami N , De With R , Weberndorfer V , Linz D , Ten Cate H , Spronk H , Koldenhof T , Tieleman RG , Schotten U , Crijns HJG , Van Gelder I , Rienstra M 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): support from the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation, CVON 2014-9: Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electrical remodelling, and Vascular destabilisation in the progression of AF (RACE V).

Purpose
To assess whether the 4S-AF scheme predicts AF progression, cardiovascular hospitalizations and mortality in patients with self-terminating paroxysmal AF.

Methods
We analysed well-phenotyped patients with paroxysmal AF from the Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilisation in the Progression of AF (RACE V study). From the 417 patients included in RACE V, 341 (82%) had echocardiography available. Patient had continuous monitoring with implantable loop recorders or pacemakers. Primary endpoint of RACE V was AF progression, defined as (1) progression to persistent or permanent AF, or (2) progression of PAF with &gt;3% burden increase. Median follow-up was 2.2 (1.6-2.8) years. Patients were given a score based on the components of the 4S-AF scheme (St, stroke=1; Sy, symptoms=2; Sb, Severity of burden=2; Su, Substrate=5) to a total maximum of 10 points (table 1). Left atrial fibrosis was not evaluated in our patients and therefore not included into the score. A score of zero (0) in the AF burden domain was given to all patients due to the presence of paroxysmal AF in all. A modified 4S-AF scheme was designed by eliminating the symptom domain, resulting in a 3S-AF scheme. Logistic regression was performed to assess AF progression and the composite endpoint of cardiovascular hospitalizations and mortality, C-statistic to assess prediction of the score, for both using the 4S-AF and the modified 3S-AF scheme.

Results
Mean age was 65 (IQR 58-71) years, 149 (44%) were women, 103 (48%) had heart failure (HFrEF 6 [2%]; HFpEF 97 [46%]), 276 (81%) had hypertension, 38(11%) had coronary artery disease and 162(48%) atherosclerosis (Table 2, Panel A). Based on the 4S-AF scheme, patients had an average score of 4.5±1.3, the majority had a score under 5 (n=272, 80%), 20% of the score was explained by the S1 domain (stroke), 16% of the score was explained by the Sy domain (symptoms), and 64% of the score was explained by the Su domain (substrate). The score points from the 4S-AF scheme did not predict the risk of AF progression (OR 1.08 95%CI 0.84 – 1.39, C-statistic 0.53) nor the composite endpoint (OR 0.79 95%CI 0.53 – 1.20, C-statistic 0.42, Table 2, Panel B). However, when excluding the Sy domain (symptoms) from the scheme, the 3S-AF scheme, it predicted the risk of progression (OR 1.54 95%CI 1.12 – 2.18, C-statistic 0.61, Table 2, Panel B).

Conclusion
In paroxysmal AF patients the 4S-AF scheme does not predict AF progression nor the composite endpoint cardiovascular hospitalizations and mortality. Although symptoms are important for choosing the treatment strategy, they may be less relevant to determine AF progression, cardiovascular hospitalization and mortality. To assess progression, the 3S-AF scheme may be more appropriate.