Outcomes in patients with anthracycline-induced cardiomyopathy undergoing left ventricular assist devices implantation.

AIMS: Improved cancer survivorship has led to a higher number of anthracycline-induced cardiomyopathy patients with end-stage heart failure. We hypothesize that outcomes following continuous-flow LVAD (CF-LVAD) implantation in those with anthracycline-induced cardiomyopathy are comparable with other aetiologies of cardiomyopathy. METHODS AND RESULTS: Using the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) from 2008 to 2017, we identified patients with anthracycline-induced cardiomyopathy who received a CF-LVAD and compared them with those with idiopathic dilated (IDM) and ischaemic cardiomyopathies (ICM). Mortality was studied using the Cox proportional hazards model. Other adverse events were evaluated using competing risk models. Overall, 248 anthracycline-induced cardiomyopathy patients underwent CF-LVAD implantation, with a median survival of 48 months, an improvement compared with those before 2012 [adjusted hazards ratio (aHR): 0.53; confidence interval (CI): 0.33-0.86]. At 12 months, 85.1% of anthracycline-induced cardiomyopathy, 86.0% of IDM, and 80.2% of ICM patients were alive (anthracycline-induced cardiomyopathy vs. IDM: aHR: 1.12; CI: 0.88-1.43 and anthracycline-induced cardiomyopathy vs. ICM: aHR: 0.98; CI: 0.76-1.28). Anthracycline-induced cardiomyopathy patients had a higher major bleeding risk compared with IDM patients (aHR: 1.23; CI: 1.01-1.50), and a lower risk of stroke and prolonged respiratory support compared to ICM patients (aHR: 0.31 and 0.67 respectively; both P < 0.05). There was no difference in the risk of major infection, acute kidney injury, and venous thromboembolism. CONCLUSIONS: After receiving a CF-LVAD, survival in patients with anthracycline-induced cardiomyopathy is similar to those with ICM or IDM. Further research into differential secondary endpoints-related disparities is warranted.

Cyanylated Cysteine: A Covalently Attached Vibrational Probe of Protein-Lipid Contacts.

Cyanylated cysteine, or beta-thiocyanatoalanine, is an artificial amino acid that can be introduced into peptides and proteins by post-translational chemical modification of solvent-exposed cysteine side chains, and thus it can be used in any protein with a suitable expression and mutagenesis system. In this study, cyanylated cysteine is introduced at selected sites in two model peptides that have been shown to bind to membrane interfaces: a membrane-binding sequence of the human myelin basic protein and the antimicrobial peptide CM15. Far-UV circular dichroism indicates that the secondary structures of the bound peptides are not influenced by introduction of the artificial side chain. Infrared spectra of both systems in buffer and exposed to dodecylphosphocholine micelles indicate that the CN stretching absorption band of cyanylated cysteine can clearly distinguish between membrane burial and solvent exposure of the artificial side chain. Since infrared spectroscopy can be applied in a wide variety of lipid systems, and since cyanylated cysteine can be introduced into proteins of arbitrary size via mutagenesis and post-translational modification, this new probe could see wide use in characterizing the protein-lipid interactions of membrane proteins.