Mapping arrhythmias in the failing heart: from Langendorff to patient

Sudden cardiac death due to ventricular arrhythmias is a major cause of mortality in patients with heart failure (HF). As HF develops, a host of changes occur at multiple levels, spanning the spectrum from subcellular/molecular to organ-system levels. These changes, collectively referred to as “cardiac remodeling,” predispose to electrical disturbances via multiple mechanisms. In humans, most arrhythmias are reentrant by nature, involving circulatory wavefront(s) that excite the heart in rapid, irregular succession. Hence, by definition, reentrant excitation occurs at the multicellular intact tissue level, and therefore, a complete understanding of its dynamics and underlying mechanisms requires investigation of electrophysiological properties (such as action potentials and calcium transients) in intact tissue preparations where cells are electrically coupled to one another. While molecular and cellular studies are critical for identifying changes in individual myocytes, only recently have we begun to understand how these complex changes can create an environment ripe for arrhythmias. In particular, the integrative technique of optical action potential mapping was used in recent years to address key questions regarding changes in network electrical properties of the failing myocardium. In the present manuscript, we review recent findings from mapping studies in the experimental laboratory as they relate to the characterization of the arrhythmic substrate of the failing heart, followed by a discussion of clinical mapping approaches used to identify key characteristics of atrial and ventricular arrhythmias in patients with HF.