Key result
RNF213 p.R4810K variant linked to ~2.2-fold higher odds of abnormal RVOT acceleration time.
Why the study?
RNF213 p.R4810K is an established risk factor for moyamoya disease and intracranial artery stenosis, but its association with insidious cardiac dysfunction in cerebrovascular disease patients was unclear.
Does RNF213 p.R4810K carriage affect right ventricular outflow tract acceleration time and other cardiac imaging parameters in patients with cerebrovascular diseases?
Cohort (n=1,312)
Yes
Does RNF213 p.R4810K carriage affect right ventricular outflow tract acceleration time and other cardiac imaging parameters in patients with cerebrovascular diseases?
Odds Ratio: 2.22 (95% CI 1.18–4.18)
p-value: p=0.014
In patients with cerebrovascular disease, carriage of the RNF213 p.R4810K variant is independently associated with prolonged right ventricular outflow tract acceleration time, suggesting subclinical pulmonary vascular changes associated with this genotype.
Supports subclinical pulmonary vascular screening in RNF213 carriers with cerebrovascular disease; hypothesis-generating and requires prospective validation before practice change.
Background RING finger protein 213 ( RNF213 ) p.R4810K is an established risk factor for moyamoya disease and intracranial artery stenosis in East Asian people. Recent evidence suggests its potential association with extracranial cardiovascular diseases, including pulmonary hypertension. We hypothesized that insidious abnormal cardiac functions are detected in RNF213 p.R4810K carriers with cerebrovascular diseases. Methods and Results We investigated patients registered in the National Cerebral and Cardiovascular Center Genome Registry between May 2017 and August 2021 who underwent echocardiography. All patients had cerebrovascular diseases. Patients with a medical history of chronic heart or pulmonary diseases were excluded. RNF213 p.R4810K was genotyped in all the patients. Of 2089 patients registered in the registry, 71 carriers and 1241 noncarriers were eligible for our analyses. The carriage of RNF213 p.R4810K emerged as a significant predictor for longer right ventricular outflow tract acceleration time in multivariable linear regression analysis (β=8.33 [95% CI, 0.92–15.74]; P =0.028). Additionally, the carriers showed increased odds of having right ventricular outflow tract acceleration time values ≥150 milliseconds (odds ratio, 2.22 [95% CI, 1.18–4.18]; P =0.014) in multivariable logistic regression analysis. Conclusions A longer right ventricular outflow tract acceleration time may reflect an increased pulmonary vascular bed induced by abnormal vascular collateral networks and dilation of capillary vessels in peripheral pulmonary arteries in the preclinical stage of RNF213 ‐related pulmonary hypertension. Thus, the right ventricular outflow tract acceleration time marker in RNF213 p.R4810K carriers suggests a biphasic course from the presymptomatic to symptomatic phase. Furthermore, vascular neurologists should carefully examine multiple organs because RNF213 ‐related vasculopathy covers systemic cardiovascular diseases. Registration URL: https://www.umin.ac.jp ; Unique identifier: UMIN000050750.
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Noda et al. (2025) conducted a cohort in Cerebrovascular diseases (n=1,312). RNF213 p.R4810K variant vs. Noncarriers was evaluated on Right ventricular outflow tract acceleration time ≥150 milliseconds (OR 2.22, 95% CI 1.18-4.18, p=0.014). Carriage of the RNF213 p.R4810K variant in patients with cerebrovascular diseases was significantly associated with increased odds of having an abnormal right ventricular outflow tract acceleration time ≥150 milliseconds (OR 2.22).
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