CMR, a Proven Tool for Assessing DMD-CM
The increased use of CMR in DMD patients in the last 15 years have
demonstrated occult cardiovascular disease before 10 years of age with
strain abnormalities and presence of LGE as young as 7.6 years of age.
There continues to be strain magnitude decline and LGE progression with
age despite normal ejection. The increase burden of LGE beyond a certain
threshold ultimately results in decrease LVEF and despite severe decline
in LVEF, HF symptoms remain absence or vague33,
79. What is most alarming is that DMD-CM
continue to progress in the setting of standard HF therapy with
angiotensin-converting enzyme inhibitors (ACE-I) on top of
steroid152. As such,
one of the major causes of mortality in the second to third decade of
life remains from DMD-CM29. Novel therapy
targeting a major cause of DMD-CM with the anti-fibrotic property of an
aldosterone inhibitor has shown some promise, though only attenuation of
disease progression compared to placebo153. These studies
have contributed to increase understanding of the natural history of
DMD-associated cardiomyopathy and resulted in increased used of CMR as
the modality of choice for assessing DMD-CM and has impacted on timing
of treatment at our institution. Newer CMR techniques with spatial
mapping of longitudinal time constant (T1 mapping) used to detect
diffuse myocardial fibrosis has been shown to be abnormal prior to
development of LGE and can provide further insight into DMD-CM natural
history 154,
155. Kierney et al., suggested that
there is increase prevalence of cardiac cause of death with improved
respiratory care 29.
However, hard outcomes measures including hospitalization and death are
challenging in pediatrics and worse in DMD as both occur as a result of
multiple factors and teasing out a primary cardiac cause is frequently
not feasible 156. As
such, surrogate biomarkers of cardiovascular disease using LVEF, LGE,
myocardial strain and potentially T1 mapping as well as ECV may overcome
the limitations of HF symptoms in DMD-CM patients. The ability to detect
DMD-CM at an earlier stage with good sensitivity and specificity by CMR
should be use as a suitable surrogate endpoint of DMD-CM to assess
therapeutic efficacy both clinically and in therapeutic trials. Unlike
this patient, our current standard of practice is to utilized CMR early
when sedation is no longer needed and when LGE is present cardiac
medication is initial and visit interval decrease. Increased in LGE
results in increase therapy even if LVEF remains normal and the patient
is younger than 10 years of age.