McDonald, William C.

Left ventricular recovery (LV) in patients with advanced heart failure (HF) supported by a durable left ventricular assist device (LVAD) is uncommon but clinically significant. There is limited understanding on the timing of LV recovery in relation to LVAD implantation. A total of 383 HF patients who underwent LVAD implantation were evaluated for LV functional improvement defined as an absolute increase in left ventricular ejection fraction (LVEF) of greater than or equal to 20% post-LVAD placement. Out of 383 LVAD patients, 39 (10.1%) demonstrated significant LV improvement. Among these, 25 (64%) patients had received LVAD less than or equal to 1 year of HF diagnosis, whereas 14 (36%) patients were implanted greater than 1 year from HF diagnosis. No significant differences in baseline imaging or hemodynamics were found between these two groups. The timing of LVAD implantation and time from LVAD to LVEF improvement was not associated with 5 year outcomes. Survival, free from HF relapse or transplant was 59% in the less than or equal to 1 year and 46% in greater than 1 year HF duration groups ( p = 0.83). Thus, LV functional improvement can occur across a broad spectrum of HF duration, suggesting that the potential for recovery is not limited to those with newly diagnosed disease.

Abstract Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are benign glioneuronal tumors that typically occur in infants, involve the superficial cerebral cortex, and have an excellent prognosis. DIA/DIG are a distinct molecular entity based on DNA methylation profiling. BRAF600 mutations are frequently reported in DIG/DIA. A recent comprehensive genetic analysis of infantile hemispheric gliomas identified 2 unique groups: group 1 harbored alterations in the receptor tyrosine kinase (RTK) genes ALK, ROS1, NTRK, and MET and group 2 harbored alterations in the RAS/MAPK pathway. We report a case of a 6.5-year-old girl who presented with seizures and right homonymous hemianopia. MRI of her brain demonstrated a large cystic/solid left hemispheric mass with remodelling of the overlying skull, consistent with a long-standing process. She underwent a gross total resection (GTR) and pathology demonstrated a DIG with a PPP1CB-ALK gene fusion (exon 5 to exon 20) identified by RNA sequencing. She remains disease free 12 months following GTR. A literature review identified 4 reported cases of pediatric brain tumors with PPP1CB-ALK gene fusions including: a 3-month-old with a hemispheric high-grade glioma which recurred 4 years later and pathology showed mature ganglioglioma, with both tumors showing the identical PPP1CB-ALK gene fusion; a 10-month-old infant with a hemispheric low-grade glioma; an infant with a “congenital” hemispheric high-grade glioma; and a child with an astrocytoma with no further clinical data. PPP1CB-ALK gene fusion appears to be a rare oncogenic driver in gliomas of infancy, including DIG.