Abstract 16699: Histopathological Characterization of Phospholamban p.Arg14del Mutation-Related Cardiomyopathy in Relation to Clinical Presentation
Background: Recently the nondesmosomal phospholamban (PLN) c.40_42delAGA (p.Arg14del) mutation has been identified in about 15% of patients with idiopathic dilated cardiomyopathy (DCM) and about 10% of patients diagnosed with arrhythmogenic right ventricular cardiomyopathy (ARVC).
Objectives: To characterize the gross and microscopic pathologic features of 16 heart specimens from patients with an identical c.40_42delAGA (p.Arg14del) mutation in the PLN-gene in relation to clinical characteristics.
Methods/Results: Complete hearts from 16 patients were collected (8 male and 8 female; mean age 46 years [range 22-71]). Ten hearts were from autopsies and six were explants. Six (6/10) autopsy cases were from patients with sudden unexpected death. The other 10 patients were evaluated by widely accepted (task force) criteria for ARVC and DCM.
A variable clinical presentation was observed, with a combination of ARVC and DCM in 4/10, only ARVC in 1/10 and only DCM in 2/10 patients.
By gross and microscopic histopathologic examination, all 16 hearts showed a predominant ARVC phenotype with fibrofatty replacement of the RV wall. LV involvement was more heterogeneous, with interstitial fibrosis and myocyte hypertrophy in 15/16 hearts, fibrofatty replacement in 8/16 hearts, most pronounced in the posterolateral and anterolateral wall, and LV dilatation in 8/16 patients.
Conclusion: Histopathologic examination of 16 cases of PLN p.Arg14del mutation-related cardiomyopathy revealed that this cardiomyopathy very often represents a combination of ARVC, defined by fibrofatty replacement of the RV wall, with involvement of the left ventricle, characterized by myocyte hypertrophy, interstitial fibrosis, variable fibrofatty replacement and sometimes LV dilatation. These pathological features were in concordance with clinical presentation since patients presented with arrhythmias, sudden death and/or left ventricular dysfunction.
- © 2013 by American Heart Association, Inc.