Optical Mapping of the Human Atrioventricular Junction

Fluorescent optical mapping of cardiac electrophysiology in animal models has produced a wealth of information about the function of the cardiac pacemaking and conduction system. However, expanding optical mapping studies to the human conduction system will significantly increase our understanding of clinically relevant phenomena, such as atrioventricular nodal reentrant tachycardia, that are difficult to fully reproduce in animal models. In this report, we present the first instance of optical mapping data recorded from the human atrioventricular junction, revealing its dual pathway electrophysiology, which is the basis of atrioventricular nodal reentrant tachycardia. Explanted human hearts (n 2) were obtained at the time of cardiac transplantation and perfused with cardioplegic solution. The atrioventricular junction was cannulated, isolated from the rest of the heart, immobilized with the excitation-contraction uncoupler blebbistatin (10 mol/L),1 and optically mapped using the voltage sensitive dye Di-4ANEPPS and a 16 16 photodiode array. In the first heart, explanted because of idiopathic cardiomyopathy, successful perfusion of the His bundle and ventricular septum, but not the atrioventricular (AV) node, was achieved. In this preparation, a junctional rhythm of 55 bpm originated from the His bundle (Figure 1). Optical action potentials (OAPs) from the His displayed diastolic depolarization and a slow upstroke with the maximum derivative of the fluorescent signal dF/ dtmax 2.8 0.5 U/s. Pacing the surrounding working ventricular myocardium produced a sharper upstroke (dF/ dtmax 37 11, P 0.001 versus His OAPs) and longer action potential duration (APD) than the His (APD80: 315 23 ms in His versus 410 3ms in ventricle, P 0.001). The activation map of the His junctional rhythm demonstrated slow conduction (7 cm/s) transversely along the His bundle (Figure 1). These data provide the first optical recordings of the human His bundle. In the second heart (with ischemic cardiomyopathy), the entire AV junction was perfused, enabling us to optically map AV nodal dual pathway characteristics for the first time in the human. We followed standard premature S1–S2 pacing protocols to unmask dual pathway electrophysiology: The S1–S2 interval was decreased until conduction block occurred in the fast pathway because of a long refractory period. The slow pathway then conducted the impulse to the His, as demonstrated by a longer interval between atrial and His activation. Previous rabbit studies demonstrated that slowversus fastpathway activation can be recognized optically2 and can be