Cardiovascular magnetic resonance findings in patients with PRKAG2 gene mutations

Pauli Pöyhönen, Anita Hiippala, Laura Ollila, Touko Kaasalainen, Helena Hänninen, Tiina Heliö, Jonna Tallila, Catalina Vasilescu, Sari Kivistö, Tiina Ojala, Miia Holmström

Autosomal dominantly inherited PRKAG2 cardiac syndrome is due to a unique defect of the cardiac cell metabolism and has a distinctive histopathology with excess intracellular glycogen, and prognosis different from sarcomeric hypertrophic cardiomyopathy. We aimed to define the distinct characteristics of PRKAG2 using cardiovascular magnetic resonance (CMR). CMR (1.5 T) and genetic testing were performed in two families harboring PRKAG2 mutations. On CMR, segmental analysis of left ventricular (LV) hypertrophy (LVH), function, native T1 mapping, and late gadolinium enhancement (LGE) were performed. Six individuals (median age 23 years, range 16-48; two females) had a PRKAG2 mutation: five with an R302Q mutation (family 1), and one with a novel H344P mutation (family 2). Three of six mutation carriers had LV mass above age and gender limits (203 g/m2, 157 g/m2 and 68 g/m2) and others (with R302Q mutation) normal LV masses. All mutation carriers had LVH in at least one segment, with the median maximal wall thickness of 13 mm (range 11-37 mm). Two R302Q mutation carriers with markedly increased LV mass (203 g/m2 and 157 g/m2) showed a diffuse pattern of hypertrophy but predominantly in the interventricular septum, while other mutation carriers exhibited a non-symmetric mid-infero-lateral pattern of hypertrophy. In family 1, the mutation negative male had a mean T1 value of 963 ms, three males with the R302Q mutation, LVH and no LGE a mean value of 918 ± 11 ms, and the oldest male with the R302Q mutation, extensive hypertrophy and LGE a mean value of 973 ms. Of six mutations carriers, two with advanced disease had LGE with 11 and 22 % enhancement of total LV volume. PRKAG2 cardiac syndrome may present with eccentric distribution of LVH, involving focal mid-infero-lateral pattern in the early disease stage, and more diffuse pattern but focusing on interventricular septum in advanced cases. In patients at earlier stages of disease, without LGE, T1 values may be reduced, while in the advanced disease stage T1 mapping may result in higher values caused by fibrosis. CMR is a valuable tool in detecting diffuse and focal myocardial abnormalities in PRKAG2 cardiomyopathy.