Systematic review finds that manifest ventricular pre-excitation can cause left ventricular dysfunction via intra-LV dyssynchrony—especially with right-sided/septal accessory pathways—and that 2D strain imaging identifies dysfunction and catheter ablation largely restores function though…

This paper has minimal direct relevance to Parkinson's therapeutic discovery because it addresses cardiac electrophysiology and structural cardiomyopathy rather than neurodegenerative mechanisms (e.g., alpha-synuclein, mitochondria, inflammation) or actionable PD targets.

Cardiac dysfunction secondary to manifest ventricular pre-excitation via accessory pathways (AP) in the absence of tachyarrhythmias is rarely studied. To evaluate pathophysiology, AP location impact, diagnostic approach, and role of catheter ablation (CA) in pre-excitation-related cardiac dysfunction without tachyarrhythmias. Electronic databases were queried for WPW/pre-excitation and cardiac dysfunction-related studies without age restrictions. A total of 34 studies met inclusion criteria, including 27 case reports/series (42 patients, 62% female) and 7 observational studies (412 participants, 41% female). Pediatric patients age ranged from infancy to 21 years and adults from 20 to 59 years. Right septal and right free-wall APs were most commonly associated with cardiomyopathy. Heart failure predominated in pediatric presentations, whereas adults most often exhibited asymptomatic LV dysfunction. Intra-LV dyssynchrony, particularly when accompanied by septal dyskinesia, emerged as a consistent pathophysiologic feature. Two-dimensional strain echocardiography (2D-STE) reliably identified LV dysfunction, localized AP, and assessed response to CA. Although cardiac function mostly normalized after successful AP ablation, irreversible myocardial changes have been reported. Preexcitation-related cardiac dysfunction in the absence of tachyarrhythmias, appears to be mediated primarily by intra-LV dyssynchrony and is most commonly associated with right-sided and septal APs. 2D-strain imaging is a useful diagnostic tool. CA typically restores cardiac function, however, irreversible myocardial changes can occur. Therefore, close surveillance and consideration of early ablation in patients with evidence of dyssynchrony are warranted. Large prospective cohort studies can further validate these findings.