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Introduction: Obesity and imbalance in lipid homeostasis contribute greatly to heart failure with preserved ejection fraction (HFpEF), the dominant form of heart failure. Few effective therapies exist to control metabolic alterations and lipid homeostasis., Objectives: We aimed to investigate the cardioprotective roles of AdipoRon, the adiponectin receptor agonist, in regulating lipid accumulation in the two-hit HFpEF model., Methods: HFpEF mouse model was induced using 60 % high-fat diet plus L-NAME drinking water. Then, AdipoRon (50 mg/kg) or vehicle were administered by gavage to the two-hit HFpEF mouse model once daily for 4 weeks. Cardiac function was evaluated using echocardiography, and Postmortem analysis included RNA-sequencing, untargeted metabolomics, transmission electron microscopy and molecular biology methods., Results: Our study presents the pioneering evidence that AdipoR was downregulated and impaired fatty acid oxidation in the myocardia of HFpEF mice, which was associated with lipid metabolism as indicated by untargeted metabolomics. AdipoRon, orally active synthetic adiponectin receptor agonist, could upregulate AdipoR1/2 (independently of adiponectin) and reduce lipid droplet accumulation, and alleviate fibrosis to restore HFpEF phenotypes. Finally, AdipoRon primarily exerted its effects through restoring the balance of myocardial fatty acid intake, transport, and oxidation via the downstream AMPKα or PPARα signaling pathways. The protective effects of AdipoRon in HFpEF mice were reversed by compound C and GW6471, inhibitors of AMPKα and PPARα, respectively., Conclusions: AdipoRon ameliorated the HFpEF phenotype by promoting myocardial fatty acid oxidation, decreasing fatty acid transport, and inhibiting fibrosis via the upregulation of AdipoR and the activation of AdipoR1/AMPKα and AdipoR2/PPARα-related downstream pathways. These findings underscore the therapeutic potential of AdipoRon in HFpEF. Importantly, all these parameters get restored in the context of continued mechanical and metabolic stressors associated with HFpEF., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Background: The advantages of multimodal digitally transformed mobile health management for patients diagnosed with mild to moderate hypertension are not yet established., Objective: We aim to evaluate the therapeutic benefits of a novel WeChat-based multimodal digital transforming management model in mobile health blood pressure (BP) management., Methods: This randomized controlled clinical trial included 175 individuals with new-onset mild to moderate hypertension who were admitted to our center between September and October 2022. The patients were randomly assigned to either the multimodal intervention group (n=88) or the usual care group (n=87). The primary composite outcome was home and office BP differences after 6 months. The major secondary outcomes were 6-month quality-of-life scores, including the self-rating anxiety scale, self-rating depression scale, and Pittsburgh Sleep Quality Index., Results: The mean home BP decreased from 151.74 (SD 8.02)/94.22 (SD 9.32) to 126.19 (SD 8.45)/82.28 (SD 9.26) mm Hg in the multimodal intervention group and from 150.78 (SD 7.87)/91.53 (SD 9.78) to 133.48 (SD 10.86)/84.45 (SD 9.19) mm Hg in the usual care group, with a mean difference in systolic blood pressure and diastolic blood pressure of -8.25 mm Hg (95% CI -11.71 to -4.78 mm Hg; P<.001) and -4.85 mm Hg (95% CI -8.41 to -1.30 mm Hg; P=.008), respectively. The mean office BP decreased from 153.64 (SD 8.39)/93.56 (SD 8.45) to 127.81 (SD 8.04)/ 82.16 (SD 8.06) mm Hg in the multimodal intervention group and from 151.48 (SD 7.14)/(91.31 (SD 9.61) to 134.92 (SD 10.11)/85.09 (SD 8.26) mm Hg in the usual care group, with a mean difference in systolic blood pressure and diastolic blood pressure of -9.27 mm Hg (95% CI -12.62 to -5.91 mm Hg; P<.001) and -5.18 mm Hg (95% CI -8.47 to -1.89 mm Hg; P=.002), respectively. From baseline to 6 months, home BP control <140/90 mm Hg was achieved in 64 (72.7%) patients in the multimodal intervention group and 46 (52.9%) patients in the usual care group (P=.007). Meanwhile, home BP control <130/80 mm Hg was achieved in 32 (36.4%) patients in the multimodal intervention group and 16 (18.4%) patients in the usual care group (P=.008). After 6 months, there were significant differences in the quality-of-life total and graded scores, including self-rating anxiety scale scores (P=.04), self-rating depression scale scores (P=.03), and Pittsburgh Sleep Quality Index scores (P<.001), in the multimodal intervention group compared with the usual care group., Conclusions: The WeChat-based multimodal intervention model improved the BP control rates and lowered the BP levels more than the usual care approach. The multimodal digital transforming management model for hypertension represents an emerging medical practice that utilizes the individual's various risk factor profiles for primary care and personalized therapy decision-making in patients with hypertension., Trial Registration: Chinese Clinical Trial Registry ChiCTR2200063550; https://www.chictr.org.cn/showproj.html?proj=175816., (©Yijun Wang, Fuding Guo, Jun Wang, Zeyan Li, Wuping Tan, Mengjie Xie, Xiaomeng Yang, Shoupeng Duan, Lingpeng Song, Siyi Cheng, Zhihao Liu, Hengyang Liu, Jiaming Qiao, Yueyi Wang, Liping Zhou, Xiaoya Zhou, Hong Jiang, Lilei Yu. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 04.12.2023.)

Background: Cardiac autonomic nerve imbalance has been well documented to provide a critical foundation for the development of acute coronary syndrome (ACS) but is not included in the postdischarge GRACE score. We investigated whether capturing cardiac autonomic nervous system (ANS)-related modulations by 24-h deceleration capacity (DC) could improve the capability of existing prognostic models, including the postdischarge Global Registry of Acute Coronary Events (GRACE) score, to predict prognosis after ACS., Method: Patients with ACS were assessed with 24-h Holter monitoring in our department from June 2017 through June 2019. The GRACE score was calculated for postdischarge 6-month mortality. The patients were followed longitudinally for the incidence of major adverse cardiac events (MACEs), set as a composite of non-fatal myocardial infarction and death. To evaluate the improvement in its discriminative and reclassification capabilities, the GRACE score with DC model was compared with a model using the GRACE score only, using area under the receiver-operator characteristic curve (AUC), Akaike's information criteria, the likelihood ratio test, category-free integrated discrimination index (IDI) and continuous net reclassification improvement (NRI)., Results: Overall, 323 patients were enrolled consecutively. After the follow-up period (mean, 43.78 months), 41 patients were found to have developed MACEs, which were more frequent among patients with DC <2.5 ms. DC adjusted for the GRACE score independently predicted the occurrence of MACEs with an adjusted hazard ratio (HR) of 0.885 and 95% CI of 0.831-0.943 ( p < 0.001). Moreover, adding DC to the GRACE score only model increased the discriminatory ability for MACEs, as indicated by the likelihood ratio test (χ 2 = 9.277, 1 df; p < 0.001). The model including the GRACE score combined with DC yielded a lower corrected Akaike's information criterion compared to that with the GRACE score alone. Incorporation of the DC into the existing model that uses the GRACE score enriched the net reclassification indices (NRIe >0 7.3%, NRIne >0 12.8%, NRI >0 0.200; p = 0.003). Entering the DC into the GRACE score model enhanced discrimination (IDI of 1.04%, p < 0.001)., Conclusion: DC serves as an independent and effective predictor of long-term adverse outcomes after ACS. Integration of DC and the postdischarge GRACE score significantly enhanced the discriminatory capability and precision in the prediction of poor long-term follow-up prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Duan, Wang, Yu, Song, Liu, Sun, Deng, Wang, Zhou, Guo, Zhou, Wang, Tan, Jiang and Yu.)