PO40 An unusual family with familial peripartum cardiomyopathy and genetic dilated cardiomyopathy: the history of 3 sisters and their daughters

Abstract Introduction Some studies reported familial clustering of Peripartum Cardiomyopathy (PPCM), and also co-occurrence with Dilated Cardiomyopathy (DCM), a phenotypically similar disease. PPCM and DCM share a genetic predisposition, with truncating variants in the TTN gene accounting for 10% to 20% of cases in both conditions. Multifactorial etiopathogenesis is also described in both, and immunology may be part of it. History of the family A 65 year-old woman (index patient, fig.1A - III3) was admitted in 2022 with de novo severe heart failure (HF) and reduced LVEF-25% (fig.1B). She was previously healthy but due to a family history of PPCM in her two oldest sisters (who have died both with DCM and HF at 52 and 55 years (y)), she was regularly followed during the last 40 years. Eight months before admission, her ECG and echocardiogram were normal. Genetic testing identified a pathogenic heterozygous variant c.78009GA, p.(Trp26003*) in the TTN gene. After 11 months of optimised therapy, LVEF was 50% (fig.1C) and remained stable thereafter. Her 42-year-old daughter (fig.1A, IV3), who had PPCM immediately after a normal pregnancy and delivery at 38y, developed acute HF (LVEF-32%) with cardiogenic shock, and the LVEF recovered slowly to 56% after 1 year (fig.1E). She is a carrier of the same TTNtvs identified in her mother. Going back 40 years, the oldest sister of the index patient (fig.1A, III1) developed severe HF at 32 years, 20 days after a normal pregnancy and delivery. She had severe LV dilation and diffuse hypocontractility (fig.1D). Without any benefit from symptomatic therapy, immunosuppression (prednisolone and azathioprine) was decided, and a rapid clinical improvement occurred, returning to everyday life. However, severely reduced LV function persisted (fig.1F, G). Her daughter, 39 years old (fig.1A, IV1), has a normal heart and had three uneventful pregnancies. She refused a genetic test. A similar clinical history had the second sister (fig.1A, II-2) who developed PPCM when she was 30y. She was also treated with immunosuppressive therapy with a good clinical response, but the reduced LV function also persisted throughout life. Her only daughter chose not to be a mother. She has a normal heart and also refused a genetic test. Conclusion PPCM and DCM may occur as individual entities, or pregnancy can act as a modifier to unmask the latent phenotype of familial TTNtvs DCM. This family illustrates the concept that the genetic predisposition to PPCM and DCM may be the same. However, different evolutive profiles can be observed throughout life in affected patients within the same family, making genotype-phenotype correlations particularly difficult in DCM and PPCM.