Depression Associated with Reduced Heart Rate Variability Predicts Outcome in Adult Congenital Heart Disease.

In adult congenital heart disease (ACHD), major depressive disorder (MDD) represents a frequent comorbidity. In non-CHD, adverse outcome is predicted by MDD and heart rate variability (HRV), whereas in ACHD their prognostic relevance is unknown. We prospectively evaluated 171 patients (age 35.6 ± 11.4 years; male 42.7%, mean observation time 54.7 ± 14.9 months). Binary regression analysis calculated the association between MDD and HRV. Cox proportional survival analysis estimated their impact on decompensated heart failure and all-cause mortality (HF/death), supraventricular and ventricular tachycardia (SVT/VT), and hospitalization due to unexpected cardiac causes. Exclusively MDD with moderate/severe symptoms showed significantly lower HRV as derived from frequency-domain analysis (Symindex) (p = 0.013). In multivariate Cox regression analysis, patients stratified according to the lower quartile of the Symindex comorbid with MDD (n = 16) exhibited poorer prognosis regarding HF/death (Hazard Ratio (HR): 7.04 (95%CI:(1.87-26.5)), SVT/VT (HR: 4.90 (95%CI:1.74-9.25)) and hospitalization (HR: 3.80 (95%CI:1.36-10.6)). An additional independent predictor was N-terminal pro-B-type natriuretic peptide elevation (p < 0.001), indicating advanced HF and heart disease complexity (p < 0.001). Autonomic nervous system dysfunction measured by altered HRV is considered to be one of the pathways linking MDD and adverse outcomes in cardiac diseases. Our results exceed the existing literature by demonstrating that MDD with decreased HRV is associated with poorer prognosis in ACHD.

Infratentorial IDH-mutant astrocytoma is a distinct subtype.

Diffuse IDH-mutant astrocytic tumors are rarely diagnosed in the cerebellum or brainstem. In this multi-institutional study, we characterized a series of primary infratentorial IDH-mutant astrocytic tumors with respect to clinical and molecular parameters. We report that about 80% of IDH mutations in these tumors are of non-IDH1-R132H variants which are rare in supratentorial astrocytomas. Most frequently, IDH1-R132C/G and IDH2-R172S/G mutations were present. Moreover, the frequencies of ATRX-loss and MGMT promoter methylation, which are typically associated with IDH mutations in supratentorial astrocytic tumors, were significantly lower in the infratentorial compartment. Gene panel sequencing revealed two samples with IDH1-R132C/H3F3A-K27M co-mutations. Genome-wide DNA methylation as well as chromosomal copy number profiling provided further evidence for a molecular distinctiveness of infratentorial IDH-mutant astrocytomas. Clinical outcome of patients with infratentorial IDH-mutant astrocytomas is significantly better than that of patients with diffuse midline gliomas, H3K27M-mutant (p < 0.005) and significantly worse than that of patients with supratentorial IDH-mutant astrocytomas (p = 0.028). The presented data highlight the very existence and distinctiveness of infratentorial IDH-mutant astrocytomas that have important implications for diagnostics and prognostication. They imply that molecular testing is critical for detection of these tumors, since many of these tumors cannot be identified by immunohistochemistry applied for the mutated IDH1-R132H protein or loss of ATRX.