Very low tidal volume, high-frequency ventilation in atrial fibrillation ablation: a systematic review.

BACKGROUND: Ventilation strategies in atrial fibrillation ablation affect procedure outcomes by influencing catheter stability. Studies have highlighted favorable atrial fibrillation (AF) ablation outcomes with the use of high-frequency jet ventilation (HFJV) which has been shown to improve lesion durability, energy delivery, and tissue contact. However, this mode of ventilation is not readily available. In this systematic review, we highlight the available data on the use of very low tidal volume, high-frequency ventilation using standard ventilators that aim to provide settings similar to HFJV during AF ablations. METHODS: Using a combination of search terms in databases and manual searches in bibliographies of identified articles, we reviewed all published data reported in the English language on the use of very low tidal volume with high-frequency ventilation during atrial fibrillation ablation. RESULTS: A total of 4 manuscripts were identified; 3 cohort studies and 1 case report. The utilization of standard ventilators with a high-frequency, very low tidal volume ventilation strategy appears to closely mimic the catheter stability benefits that HFJV ventilators provide. Across the 3 cohort identified studies, the use of this ventilation strategy was associated with improved catheter stability, tissue contact, and a decrease in radiofrequency time. No increased risk was identified compared to standard ventilation. CONCLUSION: With a purpose of limiting thoracic excursion and cardiac movement, limited and sparse studies have shown improved outcomes with a very low tidal volume, high-frequency ventilation strategy. Additional studies are needed to solidify this easily accessible and widely available mode of ventilation.

Distinct deregulation of the hypoxia inducible factor by PHD2 mutants identified in germline DNA of patients with polycythemia.

BACKGROUND: Congenital secondary erythrocytoses are due to deregulation of hypoxia inducible factor resulting in overproduction of erythropoietin. The most common germline mutation identified in the hypoxia signaling pathway is the Arginine 200-Tryptophan mutant of the von Hippel-Lindau tumor suppressor gene, resulting in Chuvash polycythemia. This mutant displays a weak deficiency in hypoxia inducible factor α regulation and does not promote tumorigenesis. Other von Hippel-Lindau mutants with more deleterious effects are responsible for von Hippel-Lindau disease, which is characterized by the development of multiple tumors. Recently, a few mutations in gene for the prolyl hydroxylase domain 2 protein (PHD2) have been reported in cases of congenital erythrocytosis not associated with tumor formation with the exception of one patient with a recurrent extra-adrenal paraganglioma. DESIGN AND METHODS: Five PHD2 variants, four of which were novel, were identified in patients with erythrocytosis. These PHD2 variants were functionally analyzed and compared with the PHD2 mutant previously identified in a patient with polycythemia and paraganglioma. The capacity of PHD2 to regulate the activity, stability and hydroxylation of hypoxia inducible factor α was assessed using hypoxia-inducible reporter gene, one-hybrid and in vitro hydroxylation assays, respectively. RESULTS: This functional comparative study showed that two categories of PHD2 mutants could be distinguished: one category with a weak deficiency in hypoxia inducible factor α regulation and a second one with a deleterious effect; the mutant implicated in tumor occurrence belongs to the second category. CONCLUSIONS: As observed with germline von Hippel-Lindau mutations, there are functional differences between the PHD2 mutants with regards to hypoxia inducible factor regulation. PHD2 mutation carriers do, therefore, need careful medical follow-up, since some mutations must be considered as potential candidates for tumor predisposition.