Abstract 314: Sensory Innervation of the Papillary Muscle: A Neural Link Between Mitral Valve Prolapse and Malignant Ventricular Arrhythmias?

Abstract

Background: Malignant mitral valve prolapse (MVP) identifies a subset of patients with MVP associated with ventricular arrhythmias (VAs), including sudden cardiac death (SCD). We hypothesized that papillary muscles, which see significant mechanical stress in MVP, are richly innervated with sensory nerves, which induce severe autonomic imbalance on the heart and may trigger malignant VAs. Methods and Results: Longitudinal sections of the anterior and posterior left ventricular papillary muscles, right ventricular outflow tract (RVOT), ventricular septum, and basolateral left ventricular wall (LV) of Yorkshire pigs (n=8) were excised, formalin-fixed, paraffin-embedded, and sectioned. Immuno-staining for protein gene product 9.5 (PGP9.5), a pan-neuronal marker, and calcitonin-gene related peptide (CGRP), a sensory afferent neuron marker, was performed. Areas of immunoreactivity (IR) for CGRP were verified by direct comparison to PGP9.5 IR. The density of CGRP was then compared across anatomical regions. The mean CGRP IR area was 1229.44 ± 116.65 μm 2 /nucleus in papillary muscles, while in the septum, basolateral LV, and RVOT, the CGRP stained areas were 699.36 ± 88.28 μm 2 /nucleus, 681.51 ± 81.90 μm 2 /nucleus, and 381.98 ± 31.14 μm 2 /nucleus, respectively (p<0.001). There was no significant difference between CGRP IR area in the anterior papillary muscle (1091.36 ± 189.82 μm 2 /nucleus) and the posterior papillary muscle (1347.79 ± 140.50 μm 2 /nucleus) (p>0.3). Conclusions: There is a significantly greater amount of afferent innervation in the papillary muscle compared to the septum, basolateral LV, and RVOT. This enrichment of afferent innervation warrants further study to understand how afferent neurotransmission during abnormal mitral valve function may impact ventricular electrophysiology.