Infiltration of conduction tissue is a major cause of electrical instability in cardiac amyloidosis

Abstract: Background: Pathology of conduction tissue (CT) and relative arrhythmias in living subjects with cardiac amyloid have never been reported. Aims: Reporting CT pathology and its arrhythmic correlations in human cardiac amyloidosis. Methods and Results: In 17 out of 45 cardiac amyloid patients, a left ventricular endomyocardial biopsy included conduction tissue sections. It was identified by Aschoff-Monckeberg histologic criteria and positive immunostaining for HCN4. The degree of conduction tissue infiltration was defined as mild when ≤ 30%, moderate when 30-70% and severe when > 70% cell area was replaced. Conduction tissue infiltration was correlated with ventricular arrhythmias, maximal wall thickness and type of amyloid protein. Mild involvement was observed in 5 cases, moderate in 3 and severe in 9. Involvement was associated with a parallel infiltration of conduction tissue artery. Conduction infiltration correlated with severity of arrhythmias (Spearman rho=0.8, p <0.001). In particular, major ventricular tachyarrhythmias requiring pharmacologic treatment or ICD implantation occurred in 7 patients with severe, 1 patient with moderate and none with mild conduction tissue infiltration. Pacemaker implantation was required in 3 patients with complete conduction section replacement. No significant correlation was observed between the degree of conduction infiltration and age, cardiac wall thickness or type of amyloid protein. Conclusion: Amyloid-associated cardiac arrhythmias correlate with extent of conduction tissue infiltration. Its involvement is independent from type and severity of amyloidosis, suggesting a variable affinity of amyloid protein to conduction tissue.