Description

Familial dilated cardiomyopathy (FDCM) is a diffuse, degenerative disease associated with loss of myocardial function and left ventricular dilatation.1 In contrast, ischaemic dilated cardiomyopathy involves specific myocardial segments, leading to fibrosis of the affected segment and subsequently impaired ventricular function.2 Nonetheless, Gulati et al reported reduced myocardial perfusion due to microvascular dysfunction in a cohort of dilated cardiomyopathy patients.3 That study did not show a patchy ischaemic pattern but rather a diffuse reduction in myocardial perfusion.

Here, we report the important finding of basal and mid-septal hypokinesia in a case of FDCM. The details of this case can revolutionise our understanding of this degenerative disorder.

A previously healthy toddler presented with respiratory distress associated with gallop heart rhythm. An echocardiogram showed a dilated left ventricle with severe systolic dysfunction and an ejection fraction (EF) of 25%, which was consistent with dilated cardiomyopathy. Genetic testing was positive for autosomal recessive nebulin-related anchoring protein (NRAP) gene-related cardiomyopathy. Her course was complicated by respiratory failure, cardiogenic shock and acute kidney injury. Subsequently, she stabilised and had mild improvement of her EF to 40% and was discharged on oral heart failure medications. Within 1 week of her discharge, she was readmitted with cardiogenic shock. At this stage, her echocardiogram showed increasing evidence for an echogenic basal and mid-septum that mimicked the picture of an ischaemic myocardium. Speckle tracking echocardiography (STE) was performed to determine if the function of this specific area was impaired compared with the rest of the myocardium. STE showed near-normal strain in four segments of the left ventricle in the four-chamber view and demonstrated that the driving force of myocardial hypokinesia in this patient was basal and mid-septal, with preserved function in the remainder of the segments (videos 1 and 2).

NRAP is a protein mainly expressed in skeletal muscles and cardiac intercalated discs.4 5 Given the specific distribution of NRAP in cardiac tissue and the specific histology of the interventricular septum (IVS), the observed pattern of septal hypokinesia cannot be explained solely by the role of NRAP in the myocardium. Intercalated discs, which harbour NRAP, are very scarce in the IVS, accounting for 8% of its whole myocardial content.6 This distribution should have given priority to lateral wall involvement over the septum. We propose that nebulin and NRAP might have other roles and different cellular distributions. In our case, two-dimensional echocardiography showed an abnormally echogenic basal septum, which is commonly encountered in ischaemic heart disease. STE showed significantly reduced strain in the echogenic segment, consistent with a patchy process. This patchy process might have been triggered by a macrovascular or microvascular event, leading to progressive fibrosis of the basal and mid-septal segments. Notably, cardiac MRI evaluation may offer additional insight due to its ability to better diagnose perfusion abnormalities. However, it could not be performed on our patient due to clinical instability. The role of NRAP in the induction of endothelial dysfunction has not yet been studied; however, similar exclusive myocardial proteins, such as MYH 6,7 8 accelerate ischaemic cardiomyopathy.

Further investigations are needed to determine if the affected segment is truly ischaemic and whether NRAP has a role in this potential ischaemia.