Digoxin did not reduce overall mortality, but it reduced the rate of hospitalization both overall and for worsening heart failure. These findings define more precisely the role of digoxin in the management of chronic heart failure.

Lysine acetyltransferase 6A (KAT6A) and its paralog KAT6B form stoichiometric complexes with bromodomain- and PHD finger-containing protein 1 (BRPF1) for acetylation of histone H3 at lysine 23 (H3K23). We report that these complexes also catalyze H3K23 propionylation in vitro and in vivo. Immunofluorescence microscopy and ATAC-See revealed the association of this modification with active chromatin. Brpf1 deletion obliterates the acylation in mouse embryos and fibroblasts. Moreover, we identify BRPF1 variants in 12 previously unidentified cases of syndromic intellectual disability and demonstrate that these cases and known BRPF1 variants impair H3K23 propionylation. Cardiac anomalies are present in a subset of the cases. H3K23 acylation is also impaired by cancer-derived somatic BRPF1 mutations. Valproate, vorinostat, propionate and butyrate promote H3K23 acylation. These results reveal the dual functionality of BRPF1-KAT6 complexes, shed light on mechanisms underlying related developmental disorders and various cancers, and suggest mutation-based therapy for medical conditions with deficient histone acylation.

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Adult patient series have shown hand-held echocardiography (echo) units (HHE) to be accurate for rapid diagnosis and triage. This is the first study to evaluate the ability of HHE to inform decision making in outpatient pediatric cardiology. New pediatric cardiology patients in outpatient clinics staffed by six pediatric cardiologists (experience 1-17 years) were prospectively enrolled if an echocardiogram (echo) was ordered during their initial visit. After history and physical examination and before a standard echo, the cardiologists performed a bedside HHE examination (GE Vscan 1.7-3.8 MHz), documented findings, and made a clinical decision. Diagnoses and decisions based on HHE were compared with final management after the standard echo. The study enrolled 101 subjects (ages 9 days to 19 years). The cardiologists considered HHE imaging adequate for decision making for 80 of the 101 subjects. For 77 of the 80 subjects with acceptable HHE imaging (68/68 normal and 9/12 abnormal standard echoes), the HHE-based primary diagnoses and decisions agreed with the final management. The sensitivity of HHE was 75 % (95 % confidence interval [CI] 43-94 %) and the positive predictive value 100 % (95 % CI 66-100 %) for pediatric heart disease. The agreement between standard echocardiography and HHE imaging was substantial (κ = 0.82). Excluding one of the least experienced cardiologists, HHE provided the basis for correct cardiac diagnoses and management for all the subjects with acceptable HHE imaging (58/58 normal and 9/9 abnormal echoes). In outpatient pediatric cardiology, HHE has potential as a tool to complement physical examination. Further investigation is needed to evaluate how value improves with clinical experience.