Nuclear Envelope Lamin-Related Dilated Cardiomyopathy: Case Series Including Histopathology

Lamin A/C mutations cause myocardial fibrosis manifesting as arrhythmogenic, noncompaction, or dilated cardiomyopathies. Fibrofatty replacement largely involves the conduction system and conduction disease commonly occurs prior to contractile dysfunction. Two young, Caucasian males, aged 34 and 25, were referred to our center for treatment of advanced heart failure. Both patients had family history of heart failure and sudden cardiac death in first degree relatives, were diagnosed with lamin A/C mutations, but had not been screened prior to disease onset. Though initial phenotypes were dilated cardiomyopathy and left ventricular-noncompaction cardiomyopathy, both patient’s disease progressed rapidly to include ventricular arrhythmias, severe global left ventricular hypokinesis, and dependence on outpatient milrinone to complete activities of daily living. Both patients received heart transplantation within 2 years of initial disease onset. Surgical pathology of the explanted hearts revealed characteristic findings of fibro-fatty degeneration of conduction system, and using light microscopy, were found to have nuclear membrane thinning, bubbling, and convolution throughout all areas sampled. Lamin A/C-related cardiomyopathy is associated with sudden cardiac death early in the disease course, warranting early consideration of implantable cardioverter defibrillator implantation, and rapid progression to end stage cardiomyopathy refractory to standard medical therapies, necessitating early referral to an advanced heart failure center. We report a newly observed and recorded finding of morphologic nuclear alterations in late-stage disease using high-power light microscopy. These alterations underscore the pathophysiology of lamin A/C-related cardiomyopathy and provide a basis for future research into disease-specific therapies.