Incidence and exploratory analysis of cancer development after new on-set atrial fibrillation
Authors: Quesada Ocete FJ , Rodriguez Pellicer C , Quesada Ocete B , Jimenez Bello J , Cervero Rubio A , Paya Chaume A , Abdala Lizarraga J , Palanca Gil V , Caro Ortega A , Del Moral Ronda V , Rubini-Costa R , Herreros-Pomares A , Paya Serrano R , Vidal-Vanaclocha F , Quesada Dorador A 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Inflammation may play an important role in the development of atrial fibrillation (AF). Some studies have suggested that cancer through inflammatory mediators may promote the development of AF (1-2). Our hypothesis was that patients with a first episode of AF might be at increased risk of developing cancer. We set out to study the incidence of cancer in the 2 years following a first episode of AF and to investigate the differences between patients (pts) who develop malignancies and those who do not.

Methods
Clinical and analytical data were collected from pts presenting with an episode of AF, diagnosed electrocardiographically, to the Emergency Department of our hospital in Spain between 2010-2015 (n=2013). After selecting pts with a first episode and excluding pts with a history of AF or cancer and those with an identified precipitating factor, a sample of 712 pts was obtained (mean age 74.3±14.7; 61.9% female). The minimum follow-up was 2 years, registering cancer occurrence and type, total mortality, emergency department attendance and hospitalization for cardiovascular causes, AF recurrences as well as bleeding and embolic events. We compared data from those who developed cancer during the 2 years after AF debut with those who did not, as well as with the incidence and types of cancer in the general population in Spain (SP) in 2012 (3).

Results
Of the 712 patients, 35 patients (4.91%) were diagnosed with cancer during the 2-year follow-up (annual incidence: 2.45% (sample) vs 0.46% (SP); p&lt;0.01). The annual incidence in our &lt;65 years old sample was 0.28% vs 0.18% in SP; p&lt;0.05. In the &gt;65 years old group, annual incidence was 2.17% (sample) vs 0.28% (SP); p&lt;0.01. There were also differences between cancer types, with non-solid neoplasms being more frequent in our sample (34.28%), followed by colorectal and breast (14.28% both) (Figure 1).
In multivariate analysis comparing patients with and without cancer in our sample, occurrence of cancer was only associated with non-typical symptoms (absence of palpitations) : 33.38% vs 14.28%; p&lt;0.05, and lower creatinine levels in patients developing cancer. Multiple correspondence analysis (MCA) also found no variables associated with cancer development (Figure 2). The mortality rate was higher in the group that developed cancer (54.28% vs 36.02%, p&lt;0.05), with no significant differences in the remaining events.

Conclusions
There is a relatively high incidence of cancer in patients with a first episode of AF (annual incidence of 2.45% after AF debut is 6.1 times the risk in the general population), in particular in the group of age &gt; 65 years old. No relevant clinical or analytical variable was able to predict the patient who will develop cancer. Further studies and exploration of new variables are needed to better assess the association between AF and cancer occurrence.