PO:12:183 | Acute effect of anti-TNF therapy on atrioventricular conduction in chronic inflammatory arthritis: a prospective cohort study

Viola Salvini¹, Riccardo Accioli¹, Anna Cantore¹, Fabio Salvadori¹, Enrico Selvi², Virgina Berlengerio², Maurizio Acampa³, Alessandra Cartocci¹, Decoroso Verrengia¹, Kateryna Miedviedieva¹, Sciaila Bernardini¹, Michele Voglino¹, Maurizio Bicchi¹, Daniela Merlotti¹, Stefania Bisogno¹, Pier Leopoldo Capecchi¹, Pietro Enea Lazzerini¹ | ¹Division of Internal Medicine, Electroimmunology Unit, University Hospital of Siena, Italy; ²Division of Rheumatology, University Hospital of Siena, Italy; ³Stroke Unit, University Hospital of Siena, Italy

Background. Several cases of advanced atrioventricular block(AVB) following anti-TNF therapy have been reported, specifically after infliximab infusion, leading to permanent pacemaker implantation. Although underlying mechanisms are substantially unknown, a single-blind, placebo-controlled, crossover study demonstrated that infliximab acutely reduces cardiac sympathetic tone, likely resulting from an abrupt drug-induced inhibition of the inflammatory reflex. Such autonomic changes, albeit transient, could have a significant impact on AV conduction in chronic inflammatory arthritis (CIA) patients, particularly in those affected with spondyloarthritis (SpA). In fact, it is increasingly accepted and supported by recent population studies that these subjects have an increased risk of severe atrioventricular (AV)-block/pacemaker implantation. It has been hypothesized that this may due to structural and immunological similarities between enthesis and aortic root (“cardiac enthesis”), in turn anchored to the AV-node. The aim of the study was to evaluate the acute impact of infliximab infusion on atrioventricular conduction in CIA patients.

Methods. Thirty-nine consecutive patients (47% females, median 47 years) with CIA underwent 12-leads electrocardiogram (ECG) monitoring during 2 h-infliximab infusion to assess PR-interval, PR-segment, heart rate (HR), and HR-variability using a frequency-domain analysis (Low Frequency [LF]/High Frequency [HF]-ratio) The Rautaharju-Soliman formula was applied to calculate HR-corrected PR-interval (PRc-interval) and PR-segment (PRc-segment). In a subgroup of 8 CIA patients (50% females), infliximab administration was preceded by a 2 h-saline infusion (placebo) during which the same parameters were assessed as control.

Results. Acute infliximab infusion, but not saline administration, was associated with an evident decrease of sympathetic tone leading to a shift towards a relative vagal prevalence (LF/HF-ratio: -0.3, p=0.003), along with a significant slowing of atrioventricular conduction (PR-interval:+15ms; p<0.001; PR-segment: 20ms; p<0.001) which persisted even after HR-correction (PRc-interval:+3.9 ms, p=0.015; PRc-segment:+14.9ms, p<0.001). In 21% of patients, in most cases SpA with enthesitic involvement (87%), infliximab-associated PRc-interval prolongation exceeded 170 ms. Compared to those who did not develop PRc-interval prolongation>170 ms, these subjects showed the most evident changes (~8-times higher PRc-interval), in the presence of significantly longer AV conduction parameters at baseline (PRc-interval: 165.9 [160.1–173.2] vs. 131.7 [120.9–148.6] ms, p<0.001; PRc-segment: 79.7 [65.2–81.2] vs. 45.7 [31.1–56.7] ms, p<0.001).

Conclusions. Infliximab infusion acutely delays AV conduction in CIA patients, likely due to indirect effects on the cardiac autonomic balance. While transient, these alterations could precipitate severe AVB, as reported in several cases after infliximab infusion. Patients affected with SpA associated with enthesitic involvement and longer AV conduction parameters at baseline may present the highest risk, as a possible expression of a pre-existing disease-associated AV delay.