Association of clonal haematopoiesis with heart failure incidence and outcomes: A systematic review and meta-analysis

Abstract

Aims: Clonal haematopoiesis (CH) is recognized as a significant risk factor for various non-haematologic conditions, including cardiovascular diseases. However, recent studies examining its relationship with heart failure (HF) have reported conflicting findings. To address these inconsistencies, the present meta-analysis aimed to evaluate the association of CH with the incidence and clinical outcomes of HF.

Methods and results: MEDLINE, Cochrane Library and Scopus were searched until 12 December 2024. Triple-independent study selection, data extraction and quality assessment were performed. Evidence was pooled using three-level mixed-effects meta-analyses. Participants (n = 57 755) with CH had significantly greater risk of new-onset HF compared to the non-CH group (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.12-1.35, p < 0.0001; I² = 0%), irrespective of a prior history of coronary artery disease. CH was also correlated with a higher risk of the composite outcome of all-cause mortality and hospitalization for HF (HHF) compared to the non-CH group in patients with established HF (HR 1.84, 95% CI 1.25-2.70, p = 0.002; I² = 0%). Specifically, CH was associated with a 95% higher risk of all-cause mortality (HR 1.95, 95% CI 1.54-2.47, p < 0.0001; I² = 0%), with a 3% increase in risk for every 1% increase in variant allele fraction. Participants with concomitant HF and CH had a 56% higher risk of HHF compared to non-CH HF patients (HR 1.56, 95% CI 1.05-2.33, p = 0.029; I² = 19%).

Conclusion: Clonal haematopoiesis is associated with an increased risk of incident HF and worse prognosis in individuals affected by HF. These findings highlight the potential of CH to contribute to a deeper understanding of HF, improve risk stratification, and support more personalized approaches to its management.

Keywords: All‐cause mortality; Clonal haematopoiesis; HFpEF; HFrEF; Heart failure; Hospitalization.

Figure 1

Forest plots of the impact of clonal haematopoiesis (CH) on the risk of incident heart failure (HF): main analysis (A), sensitivity analysis for clonal expansion of haematopoietic stem cells with a high variant allele frequency (VAF) (B); and sensitivity analysis excluding participants with established coronary artery disease (CAD) at baseline (C). ARIC, Atherosclerosis Risk In Communities; CHS, Cardiovascular Health Study; CI, confidence interval; JHS, Jackson Heart Study; HR, hazard ratio; PREVEND, Prevention of Renal and Vascular End‐stage Disease; SE, standard error; UKBB, United Kingdom Biobank; WHI, Women's Health Initiative.

Figure 2

Forest plot of the impact of clonal haematopoiesis (CH) on the risk of incident heart failure (HF) subgrouped by gene‐specific CH. ARIC, Atherosclerosis Risk In Communities; CHS, Cardiovascular Health Study; CI, confidence interval; JHS, Jackson Heart Study; HR, hazard ratio; PREVEND, Prevention of Renal and Vascular End‐stage Disease; SE, standard error; UKBB, United Kingdom Biobank; WHI, Women's Health Initiative.

Figure 3

Forest plots of the impact of clonal haematopoiesis (CH) on the composite of all‐cause mortality/hospitalization for heart failure (HHF) (A), all‐cause mortality and cardiac death (B), HHF (C); and all‐cause mortality per 1% increase in variant allele frequency (VAF) (D). CI, confidence interval; HR, hazard ratio; SE, standard error.