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 μmol/L),1 and optically mapped using the voltage sensitive dye Di-4-ANEPPS 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 slow- versus fast-pathway activation can be recognized optically2 and can be induced not only by premature stimuli but also by pacing the slow pathway directly.3 We found that both methods of inducing slow-pathway conduction worked in the human.
Figure 2A illustrates atrial pacing at 60 bpm, which depolarized the endocardial atrial layer with conduction velocities ranging from 30 cm/s to 60 cm/s (atrial APD80: 390±22 ms). After the AV nodal delay, His activation, seen in the optical recordings as a double-humped OAP, occurred at 126 ms.4 Activation between 33 ms and 114 ms was difficult to recognize in the fluorescent signals. However, nodal components of OAP upstrokes could be seen in some traces (Figure 2). Moving the pacing electrode ∼1-mm closer to the AV groove (still pacing at 60 bpm) produced conduction consistent with slow-pathway activation (Figure 2B). The pacing stimulus activated the atrial myocardium as before. However, His depolarization now occurred at 206 ms, and double-humped OAPs began slightly inferior and anterior to those in Figure 2A. Once the His was activated, longitudinal conduction was rapid (80 cm/s). S1–S2 intervals of 600 ms to 550 ms produced the same slow-pathway conduction seen in Figure 2B, and S1–S2 intervals of 530 ms to 510 ms induced an extra beat consistent with typical slow-fast AV nodal reentry (Figure 3). His electrogram morphology and amplitude also changed with the change in activating pathway (compare Figure 2A to 2B and Figures 3 to 4⇓) as shown previously in rabbits.3
Histology of the second heart is shown in Figure 4 at the locations indicated in Figures 2 and 3⇑. Activation of the large inferior nodal extension in this heart (Figure 4A), which is the possible substrate of the slow pathway, was difficult to recognize (perhaps because of its depth in the tissue).
Sources of Funding
Dr Efimov is supported by American Heart Association grant-in-aid 0750031Z.
Hucker WJ, Sharma V, Nikolski VP, Efimov IR. Atrioventricular conduction with and without AV nodal delay: two pathways to the bundle of His in the rabbit heart. Am J Physiol Heart Circ Physiol. 2007; 293: H1122–H1130.
Efimov IR, Mazgalev TN. High-resolution, three-dimensional fluorescent imaging reveals multilayer conduction pattern in the atrioventricular node. Circulation. 1998; 98: 54–57.