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Objective: This study aimed to assess biventricular function and mechanics in patients with the chronic high-altitude disease (CHAD) using cardiovascular MRI and explore the possible risk factors associated with ventricular remodeling. Methods: In this prospective study, consecutive CHAD patients and healthy controls at high-altitude (HA) and at sea level (SL) underwent cardiovascular MRI. Right ventricular (RV) and left ventricular (LV) function and global strain parameters were compared. To identify risk factors associated with ventricular remodeling, multiple linear regression analyses were used. Results: A total of 33 patients with CHAD (42.97 years ± 11.80; 23 men), 33 HA (41.18 years ± 8.58; 21 men), and 33 SL healthy controls (43.48 years ± 13.40; 21 men) were included. A Significantly decreased biventricular ejection fraction was observed in patients (all p < 0.05). Additionally, the HA group displayed lower magnitudes of biventricular longitudinal peak strain (PS) (RV, − 13.67% ± 4.05 vs. − 16.22% ± 3.03; LV, − 14.68% ± 2.20 vs. − 16.19% ± 2.51; both p < 0.05), but a higher LV circumferential PS (− 20.74% ± 2.02 vs. − 19.17% ± 2.34, p < 0.05) than the SL group. Moreover, multiple linear regression analyses revealed that HGB (β = 0.548) was related to the LV remodeling index, whereas BUN (β = 0.570) was associated with the RV remodeling index. Conclusions: With the deterioration of RV function in patients with CHAD, LV function was also impaired concomitantly. Hypoxia-induced erythrocytosis may contribute to LV impairment, while BUN was considered an independent risk factor for RV remodeling. Key Points: • A significantly lower biventricular ejection fraction was observed in patients, with a decreased magnitude of left ventricular (LV) peak systolic strain rate (radial and circumferential) and peak diastolic strain rate (all p < 0.05). • High-altitude healthy natives showed a lower biventricular longitudinal peak strain (all p < 0.05). • Hemoglobin was related to LV remodeling (β = 0.548), while BUN (β = 0.570) was independently associated with RV remodeling in CHAD patients. [ABSTRACT FROM AUTHOR]