Sacubitril/valsartan is widely used in adults with heart failure with reduced ejection fraction, but paediatric experience, especially across ventricular dysfunction phenotypes, remains limited.

To evaluate the efficacy and tolerability of sacubitril/valsartan in children with cardiomyopathy and compare outcomes in patients with predominantly right or left ventricular dysfunction.

This single-centre retrospective study included 33 patients aged 1 month to 18 years who received sacubitril/valsartan between October 2020 and October 2024. Diagnoses included arrhythmogenic right ventricular cardiomyopathy, left ventricular non-compaction, and dilated cardiomyopathy. Patients were stratified by predominant ventricular dysfunction. Echocardiographic parameters, N-terminal pro B-type natriuretic peptide, six-minute walk test, NYHA class, blood pressure, creatinine, and potassium were recorded at baseline and at 1, 3, and 6 months, and at final follow-up. Clinical outcomes included rehospitalisation, death, and heart transplantation or listing.

The cohort included 21 male patients (63.6%), and the median age was 8.6 years. Arrhythmogenic right ventricular cardiomyopathy was present in 45.5%, left ventricular non-compaction in 15.2%, and dilated cardiomyopathy in 39.4%. Left ventricular ejection fraction >45% increased from 39.4% to 72.7%. Mean N-terminal pro B-type natriuretic peptide decreased from 6309 to 3137 pg/mL (p < 0.001). NYHA class improved or remained stable in 93.3% of patients, with greater improvement in left ventricular dysfunction. During a median 17.3-months follow-up, rehospitalisation occurred in 42.4%, and 5 patients died or underwent heart transplantation/listing. Hypotension occurred in 18.2% but was manageable.

Sacubitril/valsartan was generally well tolerated and associated with improved ventricular function, biomarkers, and functional status in paediatric cardiomyopathy, particularly in left ventricular dysfunction.

Schizophrenia (SZ) is a complex disorder characterized by a range of behavioral and cognitive symptoms as well as structural and functional alterations in multiple cortical and subcortical structures. SZ is associated with reduced functional network connectivity involving core regions such as the anterior cingulate cortex (ACC) and the thalamus. However, little is known whether effective coupling, the directed influence of one structure over the other, is altered during rest in the ACC–thalamus network.

We collected resting-state fMRI and diffusion-weighted MRI data from 18 patients and 20 healthy controls. We analyzed fronto-thalamic effective connectivity using dynamic causal modeling for cross-spectral densities in a network consisting of the ACC and the left and right medio-dorsal thalamic regions. We studied structural connectivity using fractional anisotropy (FA).

We found decreased coupling strength from the right thalamus to the ACC and from the right thalamus to the left thalamus, as well as increased inhibitory intrinsic connectivity in the right thalamus in patients relative to controls. ACC-to-left thalamus coupling strength correlated with the Positive and Negative Syndrome Scale (PANSS) total positive syndrome score and with delusion score. Whole-brain structural analysis revealed several tracts with reduced FA in patients, with a maximum decrease in white matter tracts containing fronto-thalamic and cingulo-thalamic fibers.

We found altered effective and structural connectivity within the ACC–thalamus network in SZ. Our results indicate that ACC–thalamus network activity at rest is characterized by reduced thalamus-to-ACC coupling. We suggest that positive symptoms may arise as a consequence of compensatory measures to imbalanced fronto-thalamic coupling.