Genetic Risk of Peripartum Cardiomyopathy: An Updated Narrative Review of the Pre-Clinical and Clinical Literature

Peripartum cardiomyopathy (PPCM) is a form of heart failure that develops in the late stages of pregnancy or early postpartum. It accounts for 60% of deaths due to pregnancy-related cardiogenic shock, making it a significant cause of maternal mortality. Known risk factors include advanced maternal age, multiple gestation, African descent, preeclampsia, low socioeconomic status, and diabetes. Genetic factors, including truncating mutations in the TTN gene, have also been implicated in increasing susceptibility to PPCM. This narrative review synthesizes the literature from 2005 to 2025, examining both clinical and preclinical studies on genetic risk factors for PPCM. This review of 17 studies (13 clinical and 4 preclinical) reveals that genetic mutations, particularly in the TTN gene, play a significant role in PPCM risk. Additionally, alterations in genes related to sarcomere stability (filamin C), myosin function (MYH6, MYH7), heat shock proteins (BAG3, Hsp20, Hspb16), desmosome proteins, oxidative stress (signal transducer and activator of transcription 3, PGC-1α), immunity, and metabolism (CRTAM, SH2D1B, SBSPON, TNS3, PLN, SERCA) also contribute to an increased risk for PPCM. Many of these genes have been previously noted in dilated cardiomyopathy, suggesting that PPCM may be a form of dilated cardiomyopathy. This work expands on previous reviews by integrating both clinical and preclinical studies, while also addressing a gap in the literature with an updated synthesis of current findings on this topic. This work begins to lay the foundation for the potential implementation of genetic screening for PPCM, offering insights that could enable more proactive and personalized clinical care for at-risk individuals.