The vestigial fold in humans: Characterization of a potential novel target for selective cardiac sympathetic denervation

Abstract

Background: The vestigial fold is an epicardial structure related to the posterior hilum of the heart, containing the remnant of the left superior vena cava. It is the superior continuation of the ligament/vein of Marshall. Although neural structures along the human ligament/vein of Marshall have been characterized, those within the human vestigial fold remain unexplored.

Objective: This study aimed to characterize the neural structures within the human vestigial fold.

Methods: Twelve human vestigial fold samples (67% men, 50.0 ± 12.7 years) were analyzed. Nerve fascicles ≥ 50 μm in diameter were counted and characterized by immunohistochemistry staining. Percentage area of sympathetic, parasympathetic, and sensory nerve fibers (axons) within individual nerve fascicles was measured.

Results: A total of 87 nerve fascicles were analyzed. The size of the vestigial fold averaged 12.7 ± 5.1 mm in length and 3.6 ± 1.7 mm in width. Each vestigial fold contained 7.3 ± 4.2 nerve fascicles (102.0 ± 51.8 μm in diameter). The minimum distance from the epicardium to nerve fascicles was 487.1 ± 440.2 μm. Immunohistochemistry showed sympathetic predominance (Percentage area within each fascicle; sympathetic 16.9 ± 12.7%, parasympathetic 1.6 ± 1.0%, and sensory 1.2 ± 1.0%, P < .001). Representative whole-mount staining of the tissue-cleared sample also confirmed 3-dimensional distribution of the predominant sympathetic nerve fascicles within the vestigial fold.

Conclusion: The vestigial fold predominantly contains sympathetic nerve fascicles. This epicardial structure is a potential novel target for selective human cardiac sympathetic denervation, especially in cases with uncontrollable ventricular arrhythmia arising from the inferior left ventricle.

Keywords: Anatomy; Cardiac innervation; Cardiac sympathetic denervation; Neuromodulation; Vein of Marshall; Vestigial fold.