1350710 - Mitochondrial cardiomyopathy: distinctive cardiac phenotype detected by cardiovascular magnetic resonance

Left ventricular hypertrophy (LVH) in the absence of abnormal loading conditions has a broad differential diagnosis. Pathologic mitochondrial DNA variants are a rare cause of LVH, with a distinctive phenotype, mode of inheritance and often extra-cardiac manifestations. We describe the cardiac phenotype detected by CMR of 3 patients (all siblings, aged 21-39) with a near-homoplasmic pathogenic variant m.4300A >G in the MT-TI gene, which affects transfer RNA function.

Patient 1 is a 36-year-old female presenting at the age of 21. Her ECG was normal. TTE shows concentric LVH with mildly reduced EF and diastolic dysfunction. A primary prevention ICD was implanted due to frequent symptomatic PVC in addition to extensive LGE. Patient 2 is a 39-year-old patient presenting at the age of 24, his ECG shows LVH. TTE shows reduced EF with extensive LVH and diastolic dysfunction. A primary prevention ICD was implanted, and he is currently on the waiting list for heart transplantation. Patient 3 is a 21-year-old asymptomatic patient with a normal ECG. TTE shows concentric LVH with mildly reduced EF and diastolic dysfunction. No patient exhibits extra-cardiac involvement.

Diagnostic Techniques and Their Most Important Findings:

CMR did not correspond with the typical findings of sarcomere HCM, consisting of septal hypertrophy and patchy LGE in the hypertrophic segments and/or hinge points. P<strong style="mso-bidi-font-weight: normal;">atient 1 shows concentric LVH, dilatation and reduced EF 41%. Patient 2 shows asymmetrical LVH and reduced EF 38%. Patient 3 shows concentric LVH, dilatation and reduced EF 44%. With regard to the LGE images, CMR showed extensive patchy LGE in almost all segments of the LV. There are areas of intense mid-myocardial enhancement, especially in the inferoseptal segment, and also areas with almost transmural enhancement with relative wall thinning and wall motion abnormalities. This is consistent with prior descriptions of mitochondrial cardiomyopathies. T1 mapping showed increased values, particularly in the regions of LGE. Furthermore, all patients showed regional areas with an increased T2 signal, particularly in the inferoseptal region with LGE. This is not typical for sarcomeric HCM, and is suggestive of edema/inflammation. In figure 2, the progression of the disease during 9 years of follow-up is shown for patient 2. There is evident increase in LGE and increased T2 signal over time. Lastly, the right ventricle was unaffected in all patients.

Learning Points from this Case:

Pathologic mitochondrial DNA variants are a rare cause of isolated cardiomyopathy, presenting with LVH, dilatation and reduced LVEF with a maternal inheritance pattern. CMR can identify a distinctive phenotype that should raise the suspicion of an underlying mitochondrial DNA variant. Mitochondrial genotyping is not part of standard whole exome sequencing and should be requested and tested separately. Mitochondrial cardiomyopathy is associated with the progression towards end-stage heart failure and arrhythmias. Cascade screening should be carried out upon the confirmation of a mtDNA variant.