Hypoxia-inducible factor (HIF) plays a crucial role in the response to hypoxia at the cellular, tissue, and organism level. New agents under development to pharmacologically manipulate HIF may provide new and exciting possibilities in the treatment of anemia of chronic kidney disease (CKD) as well as in multiple other disease states involving ischemia–reperfusion injury. This article provides an overview of recent studies describing current standards of care for patients with anemia in CKD and associated clinical issues, and those supporting the clinical potential for targeting HIF stabilization with HIF prolyl-hydroxylase inhibitors (HIF-PHI) in these patients. Additionally, articles reporting the clinical potential for HIF-PHIs in ‘other’ putative therapeutic areas, the tissue and intracellular distribution of HIF- and prolyl-hydroxylase domain (PHD) isoforms, and HIF isoforms targeted by the different PHDs, were identified. There is increasing uncertainty regarding the optimal treatment for anemia of CKD with poorer outcomes associated with treatment to higher hemoglobin targets, and the increasing use of iron and consequent risk of iron imbalance. Attainment and maintenance of more physiologic erythropoietin levels associated with HIF stabilization may improve the management of patients resistant to treatment with erythropoiesis-stimulating agents and improve outcomes at higher hemoglobin targets.

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Aims The value of additional ablation beyond pulmonary vein isolation for atrial fibrillation (AF) ablation is unclear, especially for persistent AF. The optimal target for substrate modification to improve outcomes is uncertain. We investigate the utility of low-voltage area (LVA) substrate modification in patients undergoing catheter ablation for AF. Methods This meta-analysis was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Medline, Scopus and Cochrane Central Register of Controlled Trials were systematically searched to identify relevant studies. Risk of bias was assessed using the Cochrane risk of bias tool. Only randomized studies were included. AF patients who underwent catheter ablation with voltage-guided substrate modification targeting LVA (LVA group) vs. conventional ablation approaches not targeting LVA (non-LVA group) were compared. Results Four studies comprising 539 patients were included (36% female). Freedom from arrhythmia (FFA) in patients with persistent AF was greater in the LVA group [risk ratio (RR) 1.30; 95% confidence interval (CI) 1.03–1.64]. There was no difference in FFA in patients with paroxysmal AF between groups (RR 1.30; 95% CI 0.89–1.91). There was no difference in total procedural time (mean difference −17.54 min; 95% CI −64.37 to 29.28 min) or total ablation time (mean difference −36.17 min; 95% CI −93.69 to 21.35 min) in all included patients regardless of AF type between groups. There was no difference in periprocedural complications between groups in all included patients regardless of AF type (RR 0.93; 95% CI 0.22–3.82). Conclusion This meta-analysis demonstrates improved FFA in persistent AF patients who underwent voltage-guided substrate modification targeting LVA.