Editors' ChoiceARRHYTHMIA

Lost Rhythms and the Failing Heart

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Science Translational Medicine  05 Nov 2014:
Vol. 6, Issue 261, pp. 261ec192
DOI: 10.1126/scitranslmed.aaa1558

Heart failure affects more than 5 million Americans and can be more lethal than many cancers. Arrhythmias often occur in heart failure, but the mechanisms behind them are poorly understood. Now, in an in vitro investigation, Grand et al. explain that some heart failure arrhythmias may occur because of the strain placed on the heart’s myofibroblasts, which in turn negatively affect their neighboring cells, the beating cardiomyocytes.

The investigators cultured neonatal rat cardiomyocytes and myofibroblasts on a collagen-containing matrix that could be stretched. When different strains were applied, conduction velocities (measured with voltage-dependent dye and high-speed optical mapping) and cellular electrophysiology (assessed by using patch clamp) could be recorded. The authors created conditions that simulated both normal tissue and myocardial scar, which is commonly found in patients with heart failure. Grand et al. found that in contrast to healthy tissue, fibrotic myocardium demonstrated substantial electrophysiologic changes in response to stretching, including significant slowing of conduction velocities. This conduction-slowing effect was attributed to mechanoreceptor channels on the cultured myofibroblasts, which influenced local cardiomyocytes through gap junction coupling. This in vitro study adds insight into intra- and intercellular mechanisms that make scarred myocardium more prone to arrhythmia when subjected to stretching forces—a common scenario in the setting of acute heart failure. Translational research building on these findings could lead to new ideas to restore the heart’s rhythm and prevent death for patients with heart failure. In the future, high-risk patients could be identified by using biomarker imaging of high-risk myocardial scars, or new drug treatments could be developed to target mechanoreceptors in new ways.

T. Grand et al., Aggravation of cardiac myofibroblast arrhythmogeneicity by mechanical stress. Cardiovasc. Res. 10.1093/cvr/cvu227 (2014). [Abstract]

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