Indices of cardiac structure and function, such as left ventricular (LV) mass and ejection fraction, have been associated with risk of incident heart failure (HF), but the clinical relevance of data-driven grouping of a comprehensive set of cardiac parameters is unclear. In Multi-Ethnic Study of Atherosclerosis participants, latent class analysis was applied in the sample stratified by gender to define phenogroups on the basis of cardiovascular magnetic resonance imaging parameters of right ventricular and LV structure and function at baseline. Cox proportional hazard models in gender-stratified analyses were used to assess the association between phenogroup membership and risk of HF subtypes adjusting for potential confounders. In the 4,204 participants (mean age 61 ± 10 years, 53% women), the mean follow-up time was 14 ± 4 years for men and 15 ± 4 years for women. For both genders, 4 distinct phenogroups were identified: (1) ideal cardiac mechanics; (2) higher output/hypertrophied LV; (3) impaired ejection fraction/dilated LV; and (4) higher output/hyperdynamic (LV). Men in phenogroups 4 (hazard ratio [HR] 2.91, 95% confidence interval [CI] 1.60 to 5.31, p = 0.0005), 3 (HR 3.52, 95% CI 1.90 to 6.53, p <0.0001), and 2 (HR 3.49, 95% CI 1.94 to 6.28, p <0.0001) had higher rates of incident HF than did men in phenogroup 1, in fully adjusted models. No significant associations were found between phenogroup membership and incident HF in women. In conclusion, phenogroup membership based on cardiac structure and function in men was significantly associated with incident HF. Integration of cardiac magnetic resonance imaging variables may help identify differential risk for HF in men.
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http://dx.doi.org/10.1016/j.amjcard.2022.10.003 | DOI Listing |
Curr Opin Struct Biol
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School of Life Sciences, Westlake University, Institute of Biology, Westlake Institute for Advanced Study, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, Zhejiang, China. Electronic address:
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Allina Health, Courage Kenny Rehabilitation Institute, Minneapolis, MN.
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Children's Hospital of Philadelphia & University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States.
Robust genetic characterization of paediatric AML has demonstrated that fusion oncogenes are highly prevalent drivers of AML leukemogenesis in young children. Identification of fusion oncogenes associated with adverse outcomes has facilitated risk stratification of patients, although successful development of precision medicine approaches for most fusion-driven AML subtypes have been historically challenging. This knowledge gap has been in part due to difficulties in targeting structural alterations involving transcription factors and in identification of a therapeutic window for selective inhibition of the oncofusion without deleterious effects upon essential wild-type proteins.
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Key Laboratory of Colloid and Interface Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, State Key Laboratory of Crystal Material, Shandong University, Jinan 250100, China.
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