Abstract 16811: Phospholamban Immunostaining is a Highly Sensitive and Specific Method for Diagnosing Phospholamban p.Arg14del Cardiomyopathy
Introduction: The pathogenic p.Arg14del phospholamban (PLN) mutation causes dilated and/or arrhythmogenic cardiomyopathy and is associated with increased risk of malignant ventricular arrhythmias and severe heart failure. Recently, we showed that PLN p.Arg14del cardiomyopathy may be diagnosed in whole heart specimens by PLN immunohistochemistry which allowed microscopic detection of PLN-containing aggregates in cardiomyocytes in dense perinuclear aggresomes.
Objective: To determine the accuracy (sensitivity and specificity) of PLN immunohistochemistry in apical left ventricular myocardial specimens, harvested during left ventricular assist device (LVAD) implantation, to diagnose PLN p.Arg14del cardiomyopathy.
Methods: Included were myocardial LVAD specimens from 26 diverse genetic cardiomyopathy cases with known gene mutations (5 PLN p.Arg14del cases and 21 cases with other pathogenic cardiomyopathy mutations). Immunohistochemistry (IHC) with monoclonal phospolamban antibody 2D12 (1:10000, Abcam, Cambridge, MA, USA) was used to visualize PLN protein aggregation. Blinded histological assesment of PLN aggregates in LVAD samples was performed by 2 independent observers (AJHS and WPtR).
Results: IHC analysis revealed typical dense perinuclear globular PLN-positive aggregates (representing aggresomes) in all 5 PLN p.Arg14del cases. In 20 non-PLN cases no IHC staining was found and in one non-PLN case we observed a staining artifact.
Conclusions: In this genetic cardiomyopathy cohort, PLN IHC analysis in LVAD biopsies was found to have very high sensitivity (100%) and specificity (95%) for demonstration of PLN protein aggregates in PLN p.Arg14del cardiomyopathy. In clinical practice PLN IHC analysis can be very helpful in the diagnostic workup of this cardiomyopathy, even more so if genetic analysis cannot be performed.
Author Disclosures: W. te Rijdt: None. Z. van der Klooster: None. J. van Tintelen: None. D. Dooijes: None. F. Asselbergs: None. M. van den Berg: None. A. Vink: None. A. Suurmeijer: None.
- © 2016 by American Heart Association, Inc.