Impact of mobilization in patients with short-term mechanical circulatory support such as Levitronix® CentriMag as a bridge to heart transplantation.

INTRODUCTION: Despite the benefits of mobilisation in the critical patient, the evidence in patients with Levitronix® CentriMag as a bridge to heart transplantation (HT) is scarce. The objective of this study is to analyze the impact of mobility on these patients. METHODS: Retrospective observational study of patients who received a HT with Levitronix® CentriMag admitted between 2010 and 2019 to a tertiary hospital. Degree of mobility and nutritional status were assessed at the time of HT. Outcomes including infections, length of hospital admission and mortality were evaluated. RESULTS: 27 patients were included and divided in two groups according to degree of mobility (22 with low mobility and 5 with high mobility). 90-day survival after HT was 63.6% in patients with low mobility and 80% in high mobility group; no statistically significant differences were observed. No differences were observed regarding ICU discharge after HT at 30 days. Nevertheless, lower albumin levels were observed in low mobility group (24,5 g/L (IQR: 23-30) vs 33 g/L (IQR: 26-36); p = .029). Invasive mechanical ventilation (IMV) post HT was longer in patients with low mobility (p = .014). There were no significant differences in appearance of pressure ulcers, or post HT infections among mobility groups. CONCLUSIONS: Patients with high mobility had a shorter time of IMV and a better nutritional status. No complications were observed associated to mobility. No differences were observed between the degree of mobility and 90-day mortality, ICU stay or post HT adverse events.

Neurohormonal activation induces intracellular iron deficiency and mitochondrial dysfunction in cardiac cells.

BACKGROUND: Iron deficiency (ID) is common in patients with heart failure (HF) and is associated with poor outcomes, yet its role in the pathophysiology of HF is not well-defined. We sought to determine the consequences of HF neurohormonal activation in iron homeostasis and mitochondrial function in cardiac cells. METHODS: HF was induced in C57BL/6 mice by using isoproterenol osmotic pumps and embryonic rat heart-derived H9c2 cells were subsequently challenged with Angiotensin II and/or Norepinephrine. The expression of several genes and proteins related to intracellular iron metabolism were assessed by Real time-PCR and immunoblotting, respectively. The intracellular iron levels were also determined. Mitochondrial function was analyzed by studying the mitochondrial membrane potential, the accumulation of radical oxygen species (ROS) and the adenosine triphosphate (ATP) production. RESULTS: Hearts from isoproterenol-stimulated mice showed a decreased in both mRNA and protein levels of iron regulatory proteins, transferrin receptor 1, ferroportin 1 and hepcidin compared to control mice. Furthermore, mitoferrin 2 and mitochondrial ferritin were also downregulated in the hearts from HF mice. Similar data regarding these key iron regulatory molecules were found in the H9c2 cells challenged with neurohormonal stimuli. Accordingly, a depletion of intracellular iron levels was found in the stimulated cells compared to non-stimulated cells, as well as in the hearts from the isoproterenol-induced HF mice. Finally, neurohormonal activation impaired mitochondrial function as indicated by the accumulation of ROS, the impaired mitochondrial membrane potential and the decrease in the ATP levels in the cardiac cells. CONCLUSIONS: HF characteristic neurohormonal activation induced changes in the regulation of key molecules involved in iron homeostasis, reduced intracellular iron levels and impaired mitochondrial function. The current results suggest that iron could be involved in the pathophysiology of HF.

Familial evaluation reveals a distinct genetic cause in a large Spanish family with neurofibromatosis 1 and hypertrophic cardiomyopathy.

Neurofibromatosis 1 (NF1) is an autosomal dominant disorder characterized by café-au-lait spots, intertriginous freckling, and multiple neurofibromas. Classically, it has been described that hypertrophic cardiomyopathy (HCM) may be a cardiovascular manifestation of neurofibromatosis 1, although the relationship between these two entities has not been fully established. We report a large Spanish family carrying a pathogenic truncating variant in NF1 (p.Arg2258Ter) causing neurofibromatosis 1, and a pathogenic missense variant in MYH7 (p. Arg453Cys), causing hypertrophic cardiomyopathy independently. A complete penetrance was observed in both genetic diseases, reinforcing the notion of deleterious effects of both rare variants. According to our report, hypertrophic cardiomyopathy in patients with NF1 should not be considered as part of the clinical spectrum in all cases. A careful and comprehensive assessment, including family evaluation and genetic testing for HCM should be considered as part of the diagnostic work-up in individuals presenting with both phenotypes.