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.