Arrhythmic risk in rheumatoid arthritis: the driving role of systemic inflammation

Abstract

When compared to the general population, patients with rheumatoid arthritis (RA) have an overall standard mortality ratio of approximately two, with more than 50% of premature deaths attributable to cardiovascular disease (CVD). Moreover, RA patients were twice as likely to experience sudden cardiac death (SCD) compared with non-RA subjects, as a putative consequence of an increased incidence of malignant arrhythmias. Accordingly, mounting data indicate that in patients affected with RA the risk of developing rhythm disturbances, particularly tachyarrhythmias, is high.

Although a number of papers reviewing the problem of cardiovascular involvement in RA are currently available, the main focus is on the mechanisms of accelerated atherosclerosis and related ischemic consequences in the clinical setting. On the contrary, only little consideration has been specifically given to the arrhythmic risk so far. In the light of this concern, in the present paper we reviewed the topic with the aim to put together the apparently fragmentary existing information, with particular attention to the putative role of chronic systemic inflammation characterizing the disease. In fact, although the underlying mechanisms accounting the arrhythmogenic substrate in RA are probably intricate, the leading role seems to be played by inflammatory activation, able to promote arrhythmias either indirectly, by accelerating the development of structural CVD, and directly by affecting cardiac electrophysiology.

In this view, lowering inflammatory burden through an increasingly tight control of disease activity may represent the most effective intervention to reduce arrhythmic risk and prevent life-threatening complications in these patients.

Introduction

In the last years, a growing body of evidence indicates that patients with rheumatoid arthritis (RA) have an increased risk of death when compared to age- and sex-matched subjects in the general population, with an overall standard mortality ratio (SMR) of approximately two [1], [2]. Such an excess of mortality is mainly due to cardiovascular disease (CVD), responsible for about a half of premature deaths observed in these patients [1], [2]. The concomitant evidence that in RA the risk of sudden cardiac death (SCD) is two-times higher than it is in non-RA subjects [3], suggests that an increased incidence of malignant arrhythmias may explain, at least in part, the higher mortality observed in RA.

Although the mechanisms accounting for this arrhythmogenic substrate are not well known as yet, the fact that both ischemic heart disease (IHD) and heart failure (HF) are significantly more prevalent in RA patients than in the general population (about 1.5 to 2.0-fold) [4] largely contributing to RA mortality [5], [6], suggests that the structural modifications characterizing these heart diseases may promote arrhythmic risk in RA. Indeed, it is well established that IHD and HF are highly associated with the development of life threatening arrhythmias and SCD in the general population [7], [8]. Nevertheless, increasing evidence indicates that arrhythmogenicity in RA may be also the result of non-structural heart abnormalities of electrophysiological origin. These factors, by possibly amplifying the arrhythmic risk driven by IHD- and HF-associated structural damage, may help explain the finding that in RA the excess of deaths results not only from an increased CVD morbidity but also from a higher case fatality [2].