**3. Pathophysiology of arrhythmias encountered in patients with ventricular assist devices**

Pediatric patients with decompensated heart failure are at increased risk for tachyarrhythmias. Patients requiring VAD therapy are at high risk for atrial and ventricular arrhythmias. In one cohort, over 70% of children with VADs experienced an arrhythmia with nearly 20% developing new arrhythmia while on VAD therapy [11]. Ventricular tachycardia is consistently the most common arrhythmia reported post VAD implantation, with documentation of monomorphic and polymorphic ventricular tachycardia. The presence of ventricular arrhythmia prior to VAD therapy has been found to be predictive of ventricular arrhythmia post VAD implantation [17]. More than half of pediatric patients with arrhythmia prior to VAD therapy continue to experience arrhythmia while on VAD [11].

One main mechanism by which heart failure increases the risk of atrial fibrillation is through increased left atrial pressures [18]. Anisotropy and reduced atrial conduction velocity develop from scar secondary to the chronic increased left atrial pressure, promoting atrial tachyarrhythmia. Structural remodeling, atrial myopathy, and maladaptive gene expression are other mechanisms by which heart failure can facilitate the development of atrial fibrillation. Heart failure results in a proinflammatory state that leads to structural remodeling mediated by diffuse fibrosis, the consequence of which includes electrophysiologic heterogeneity and slowed conduction [19]. Associated left ventricular diastolic dysfunction transfers increased left ventricular filling pressure to the left atrium. Prolonged elevated left atrial pressure can result in dispersion of refractoriness. Studies have demonstrated prolongation in atrial refractoriness, P-wave duration, and conduction time in patients with atrial fibrillation [20]. Increased left

atrial pressure results in decrease in cardiac calcium ion channels, leading to calcium overload, increased diastolic calcium lead, and prolonged action potential duration. Increased calcium content has been demonstrated to portend afterdepolarizations from the pulmonary veins that serve as triggers for atrial fibrillation [21, 22].

There are several factors related to the underlying heart failure that may stimulate development of ventricular arrhythmia. Ventricular dysfunction has been found to be an independent risk factor for arrhythmia associated with VAD therapy [11, 23]. This is not unexpected as severe ventricular dysfunction itself can promote arrhythmia. The development of chamber enlargement, myocardial scar, and subendocardial ischemia can result in myocardial injury and become arrhythmogenic. Focal areas of scar result in a heterogenous area of healthy and infarcted myocardium with different conduction properties and refractoriness in close proximity [24]. This leads to anisotropy and areas of slow conduction, which is prime for reentry. Neurohormonal activation, enhanced catecholamines, electrolyte abnormalities, and altered calcium handling can also contribute to an environment prone to arrhythmia.

VAD implantation has been associated with electrophysiologic changes. Prolongation of the QT and corrected QT interval have been observed post VAD implantation and associated with tachyarrhythmia [25, 26]. Changes in channel regulation including upregulation of the Na+/Ca2+ exchange and downregulation of the voltage-gated K+ channel, may contribute to increase in action potential duration and development of delayed afterdepolarizations [27]. The VAD implantation process and presence of the device itself can prompt arrhythmia. Apical scar at the site of VAD inflow cannula insertion can contribute to reentrant ventricular tachyarrhythmias. Suction events where the VAD inflow cannula engages the ventricular wall result in decreased device output, reducing cardiac function support and increasing the risk for ventricular arrhythmia [28]. High VAD pump speed, VAD inflow cannula position, and low patient intravascular volume are contributing factors that increase the risk of suction events [13].
