Association of Clonal Hematopoiesis of Indeterminate Potential with Incident Heart Failure with Preserved Ejection Fraction

BackgroundClonal hematopoiesis of indeterminate potential (CHIP) was recently identified as a risk factor for incident heart failure (HF). Whether CHIP is associated selectively with risk of heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) subtypes is unknown ObjectivesTo evaluate whether CHIP is associated with incident HF subtypes, HFrEF versus HFpEF. MethodsWe obtained CHIP status from whole genome sequencing of blood DNA in participants without prevalent HF from a multi-ethnic sample of post-menopausal women without prevalent HF (N=5,214) from the Womens Health Initiative (WHI). Cox proportional hazards models were performed, adjusting for demographic and clinical risk factors. ResultsCHIP was significantly associated with a 42% (95%CI 6%, 91%) increased risk of HFpEF (P=0.02). In contrast, there was no evidence of association between CHIP and risk of incident HFrEF. When the three most common CHIP subtypes were assessed individually, the risk of HFpEF was more strongly associated with TET2 (HR=2.5; 95%CI 1.54, 4.06; P<0.001), than DNMT3A or ASXL1. ConclusionCHIP, particularly mutations in TET2, represents a potential new risk factor for incident HFpEF.