Cardiomyopathy in DMD - what should we know?

A 10 year old child with Duchene muscular dystrophy came for follow up after 6 months, delayed because of the lockdown during the COVID pandemic.

The lockdown had deprived him of any regular physiotherapy and medications were also irregular because of erratic supplies in his village. He had stopped walking the last 2 months. He had some tachycardia.

We got an echocardiogram (ECHO) done. It revealed moderate LV dysfunction with an LV ejection fraction of 39%.

It was a good opportunity to review the literature on what is optimal therapy for cardiomyopathy in DMD today and what is new( https://doi.org/10.1542/peds.2018-0333I)

• As respiratory support for DMD patients has improved, cardiac contributions to morbidity and mortality are gaining supremacy.
• It is often difficult to pick up cardiac dysfunction clinically in patients with DMD due to their restricted ambulation.
• Early diagnosis and treatment results in improved cardiac remodelling.
• In the new DMD care guidelines, annual cardiac evaluations are recommended from the time of diagnosis. More frequent evaluations are required for those with established cardiomyopathy.
• Cardiac MRI (CMRI) is recommended over ECHO because of suboptimal acoustic windows and inaccurate estimation of systolic function with the latter.
• Subepicardial fibrosis on CMRI is picked up much earlier than changes in ejection fraction/fractional shortening on ECHO.
• The pattern of late gadolinium enhancement is an important biomarker for myocardial fibrosis.
• Strain imaging (on ECHO/CMRI) is a new tool to pick up regional wall abnormalities.
• In the future T1 mapping which evaluates extracellular volume will identify early diffuse fibrosis.
• The NIH working Group recommends starting ACE inhibitors or ARB's by age 10 (Perindopril was used in the trial by Duboc et al)
• For established cardiac involvement (on CMRI/ECHO) the combination of ACEi and aldosterone agonists may have an edge over ACEi alone.
• Decreased ejection fraction is closely linked to ventricular arrhythmias.
• ICD's are recommended for those with a sustained VT/ resuscitated cardiac arrest.
• However preemptive ICD's are still controversial in DMD patients with EF < 35% or ill sustained VT.
• Gene therapies like the exon skipping drugs ( eg Eteplirsen) are less efficacious in the cardiac muscle in animal studies vis a vis skeletal muscle.

Late gadolinium enhancement (LGE) of the inferolateral and anterolateral free wall of the left ventricle is very characteristic of DMD. It is hypothesised to be due to mechanical stress on a structurally damaged myocardium. Viral myocarditis bears an uncanny similarity to this. Interestingly in entero viral myocarditis, the myocardial damage was noted to be due to cleavage of dystrophin.

LGE is picked up before LV dysfunction on ECHO. Anti failure medications started after development of LGE has been shown to delay and probably reverse the remodelling process. (https://www.researchgate.net/deref/http%3A%2F%2Fdx.doi.org%2F10.4330%2Fwjc.v4.i5.173?_sg%5B0%5D=HFeIzFrptTM0CJRLths4NxFgooAeaoZwcCOrOXiu6aW91SJN3M7iAz2Z0tocRGRr6MVGZh4N5NMAeU5l8Qk0_BvyXQ.bHCd8lktPiMjY2ZB4Qnk0UFVzeruLtDHz0iBCXhXk8c4uer4noSbVPFL_ZRiC8H_i6iabfEulTJgx9OvcUBSJQ)

There appears to be a case for CMRI in DMD.