Cat eye syndrome chromosome region, candidate 1 is a novel prognostic biomarker in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) exhibits great prognostic heterogeneity, necessitating the identification of high-risk patients for timely treatment. This study aimed to find novel prognostic biomarkers directly from diseased cardiac tissue to improve risk stratification of HCM. We utilized a myocardial transcriptome discovery cohort ( n = 246; median follow-up 6.8 years) alongside two independent plasma validation cohorts (Beijing, n = 1,238; follow-up 2.5 years; Xi’an, n = 402; follow-up 4.8 years). The primary and secondary endpoints were cardiovascular death and sudden cardiac death (SCD), respectively. In the discovery cohort, myocardial expression of CECR1 (cat eye syndrome chromosome region, candidate 1, also known as ADA2 , Adenosine Deaminase 2) demonstrated the strongest association with cardiovascular death ( P = 9.6 × 10 –5 ). Plasma CECR1 levels correlated modestly but significantly with myocardial expression. In the Beijing validation cohort, decreased plasma CECR1 predicted increased risks of cardiovascular death (adjusted hazard ratio (HR) 3.731, P < 0.001) and SCD (adjusted HR 7.398, P < 0.001), with areas under the curves (AUCs) of 0.720 and 0.798, respectively. These findings were replicated in the Xi’an validation cohort. Integrating plasma CECR1 into the HCM Risk-SCD model significantly enhanced its predictive performance, increasing the AUC from 0.723 to 0.845 ( P = 0.031) in the Beijing validation cohort and consistently improving it from 0.600 to 0.781 ( P = 0.018) in the Xi’an validation cohort. In conclusion, CECR1 represents a novel prognostic biomarker of HCM. Measurement of CECR1 may improve risk stratification by facilitating the identification of individuals at higher risk of cardiovascular mortality. CECR1 assessment may provide additional information for SCD risk evaluation and support clinical decision-making regarding implantable cardioverter-defibrillator therapy.