International journal of cardiology · 2025
Clinical significance of mitochondrial dynamics-related miRNAs in the superacute phase of acute heart failure in patients presenting to the emergency department.
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Shirakabe Akihiro, Ikeda Yoshiyuki, Uchikado Yoshihiro, Okazaki Hirotake, Matsushita Masato, Sawatani Tomofumi, Shigihara Shota, Tani Kenichi, Morooka Masaki, Kobayashi Nobuaki, Ohishi Mitsuru, Sadoshima Junichi, Asai Kuniya
Аннотация
BACKGROUND: Mitochondria are dynamic organelles whose morphology can change through fusion and fission. The role of these mitochondrial dynamics in cardiomyocytes has not been evaluated in patients with acute heart failure (AHF).
METHODS AND RESULTS: Two hundred seventy-three AHF patients and 374 control patients who attended a cardiovascular outpatient clinic were prospectively analyzed. Blood samples were collected within 15 min of admission from AHF patients (AHF group) and control patients who visited a daily cardiovascular outpatient clinic (control group). Mitochondrial dynamics-related RNAs were compared between the two groups, and long-term prognosis (1000-day mortality) was evaluated across RNA quartiles. The miR-140-3p and miR-485-3p levels in the AHF group (median 6.73, range 2.75-14.55; median 0.45, range 0.13-1.86) were significantly (p = 0.002 and p = 0.049) lower than those in the control group (median 8.61, range 3.37-34.12; median 0.78, range 0.15-3.52), respectively. Cardiac biomarkers, including N-terminal pro-BNP, heart-type fatty acid-binding protein, and high-sensitivity troponin, were significantly higher in the low-miR-140-3p group than in the middle- and high-miR-140-3p groups. Kaplan-Meier curve analysis revealed that all-cause mortality within 1000 days was significantly higher in the low-140-3p group than in the middle- and high-miR-140-3p groups. Cox regression analysis revealed that the low-140-3p group was an independent predictor of 1000-day mortality (hazard ratio 1.567; 95 % confidence interval 1.004-2.444; p = 0.048).
CONCLUSION: Impaired mitochondrial dynamics were observed in the acute phase of AHF. In particular, a mitochondrial fission-related miRNA (miR-140-3p) was independently associated with adverse outcomes.
METHODS AND RESULTS: Two hundred seventy-three AHF patients and 374 control patients who attended a cardiovascular outpatient clinic were prospectively analyzed. Blood samples were collected within 15 min of admission from AHF patients (AHF group) and control patients who visited a daily cardiovascular outpatient clinic (control group). Mitochondrial dynamics-related RNAs were compared between the two groups, and long-term prognosis (1000-day mortality) was evaluated across RNA quartiles. The miR-140-3p and miR-485-3p levels in the AHF group (median 6.73, range 2.75-14.55; median 0.45, range 0.13-1.86) were significantly (p = 0.002 and p = 0.049) lower than those in the control group (median 8.61, range 3.37-34.12; median 0.78, range 0.15-3.52), respectively. Cardiac biomarkers, including N-terminal pro-BNP, heart-type fatty acid-binding protein, and high-sensitivity troponin, were significantly higher in the low-miR-140-3p group than in the middle- and high-miR-140-3p groups. Kaplan-Meier curve analysis revealed that all-cause mortality within 1000 days was significantly higher in the low-140-3p group than in the middle- and high-miR-140-3p groups. Cox regression analysis revealed that the low-140-3p group was an independent predictor of 1000-day mortality (hazard ratio 1.567; 95 % confidence interval 1.004-2.444; p = 0.048).
CONCLUSION: Impaired mitochondrial dynamics were observed in the acute phase of AHF. In particular, a mitochondrial fission-related miRNA (miR-140-3p) was independently associated with adverse outcomes.