Infiltration of Conduction Tissue Is a Major Cause of Electrical Instability in Cardiac Amyloidosis.

BACKGROUND: The pathology of conduction tissue (CT) and relative arrhythmias in living subjects with cardiac amyloid have never been reported. AIMS: To report 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 five cases, moderate in three and severe in nine. Involvement was associated with a parallel infiltration of conduction tissue artery. Conduction infiltration correlated with the severity of arrhythmias (Spearman rho = 0.8, p < 0.001). In particular, major ventricular tachyarrhythmias requiring pharmacologic treatment or ICD implantation occurred in seven patients with severe, one patient with moderate and none with mild conduction tissue infiltration. Pacemaker implantation was required in three 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. CONCLUSIONS: Amyloid-associated cardiac arrhythmias correlate with the 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.

Myocarditis in hypertrophic cardiomyopathy patients presenting acute clinical deterioration.

AIM: We sought to determine whether myocarditis can be a major cause of acute electrical instability or clinical deterioration in HCM patients. METHODS AND RESULTS: A total of 119 HCM patients (69 M/50F, mean age 41 +/- 8), 42 with acute clinical deterioration and 77 clinically stable, underwent cardiac catheterization with left ventricular endomyocardial biopsy and gene analysis of major sarcomeric proteins. Endomyocardial tissue was processed for histology, immunohistochemistry, and polymerase chain reaction for the most common cardiotropic viruses. Controls were surgical samples from 50 patients with mitral stenosis. All 119 patients showed histological findings suggestive of HCM. In addition, CD45RO+ lymphocytes (> or =14/mm(2)) with focal necrosis of the adjacent severely hypertrophied and often disorganized myocytes, consistent with an overlapping active myocarditis, were observed in 28 of 42 unstable and none of 77 stable HCM patients. A viral genome was detected in 14 of 28 patients with myocarditis and in none of HCM patients without and in none of controls. No correlation between sarcomeric protein gene mutations and HCM clinical profile was observed. CONCLUSION: Myocarditis, often viral, represents a common cause of acute clinical deterioration in HCM. Its recognition can potentially affect disease prognosis and treatment.