Patient perspectives on gene therapies and gene editing for familial cardiomyopathies

Gene replacement and gene editing therapies for cardiomyopathies are in early-phase clinical trials. However, limited data exist on patient perspectives. We assessed adult familial cardiomyopathy patient perspectives towards the clinical implementation of somatic genetic therapies. Patients completed a demographic survey and semi-structured interview. A codebook was developed deductively and inductively, and thematic analysis was performed. Twenty-one participants with genetic and clinical diagnoses of either hypertrophic cardiomyopathy (17) or dilated cardiomyopathy (4) completed interviews. Participants ranged from age 38 to 80 (mean 57) and were 57% female. Four main themes influence participants’ decision-making for hypothetical pursuit of genetic therapies: (1) perceived clinical severity (2) impact on condition and familial benefit (3) treatment safety, mechanism, and delivery (4) ethical and social considerations. Those who described a severe clinical presentation expressed increased interest in genetic therapies and an increased willingness to accept risks, particularly if the therapy targeted the root cause or halted condition progression. Participants voiced uncertainties about the safety and long-term consequences of these therapies. Many believed that clinical severity should be prioritized for genetic therapies regardless of age; some felt younger individuals benefit more, avoiding lifelong treatment. Family members’ negative experiences with cardiomyopathies also influenced the decision-making process. When comparing genetic therapies to existing treatment options, genetic therapies were the most preferred treatment while ICDs were the least preferred. Around one-third of participants expressed hypothetical interest in participating in clinical trials or early adoption post-FDA approval. Ethical and social concerns included misuse of these therapies, their egalitarian distribution, and loss of beneficial genetic traits. Patients’ support for and concerns about genetic therapies for cardiomyopathies highlight the need for clear communication of benefits, risks, uncertainties, and comparison with other existing treatment options. Including patients in discussions about the ethical and social impacts of these therapies is essential.