Frontiers in Cardiovascular Medicine · Oct 30, 2026
Clonal Haematopoiesis of Indeterminate Potential and Postoperative Neuroinflammation in Cardiac Surgery: A Hypothesis-Generating Review
By Igor Bryukhovetskiy, Oleg Pak, Iakov Samushia et al.
In today's cardiac surgical practice, the preservation of cognitive capacity has become a pivotal benchmark of successful outcome. Nonetheless, postoperative cognitive dysfunction (POCD) is observed in 30–80% of patients in the early postoperative phase, and a considerable fraction exhibit persistent deficits. Conventional risk determinants account for only a portion of this variability. Clonal haematopoiesis of indeterminate potential (CHIP) — somatic mutations within haematopoietic stem cells driving clonal outgrowth of mutant immune cells that overproduce IL-1β, IL-6, and TNFα — has emerged as a biologically plausible enhancer of perioperative inflammation. In the context of cardiopulmonary bypass, CHIP may amplify the systemic cytokine surge, theoretically setting the stage for neuroinflammation via compromise of the blood–brain barrier, microglial activation, and neuronal damage. The prevalence of CHIP reaches 10–20% in the general population over 70 years (at a variant allele frequency (VAF) threshold of ≥2%), and up to 44% in selected cardiac surgery cohorts using a VAF threshold of ≥1%; clones with VAF ≥2% are associated with a modestly increased risk of stroke (HR 1.20). Nevertheless, direct proof that CHIP contributes to POCD or delirium after cardiac surgery is presently unknown. This review puts forward an interpretive framework for cardiac surgery specifically, regarding CHIP-driven inflammation as a potential systemic contributor to neurological vulnerability, while underscoring that this remains a hypothesis necessitating prospective validation. We discuss molecular underpinnings, clinical epidemiology, and future investigative paths, encompassing targeted anti-cytokine regimens (IL-1β, IL-6, JAK2 inhibitors) and experimental cell-based strategies for rectifying the bone marrow microenvironment. We conclude that curbing CHIP-associated inflammation constitutes a promising research direction, but its clinical translation requires well-designed trials.