Causal Relationship: Association Between Atrial Fibrillation and Zoledronic Acid in the Setting of Humoral Hypercalcemia of Malignancy

Atrial Fibrillation (AF) is the most common sustained arrhythmia, and its incidence and prevalence are increasing both in the United States and globally [1,2]. The prevalence of AF in the United States was estimated to be 5.2 million in 2010, with an expected rise to 12.1 million by 2030 [1]. Corresponding estimates for the incidence of AF in the U.S. were 1.2 million cases in 2010, projected to increase to 2.6 million cases by 2030 [1]. The rate of AF diagnosis varies according to factors such as education, income [3], clinical presentation [4,5], and genetic predisposition [4]. AF is associated with a 1.5- to 2-fold increased risk of mortality [6,7]; studies suggest that this risk may be higher in women than in men [6]. Meta-analyses have also shown that AF is linked to an increased risk of several adverse outcomes, including a 2.4-fold risk of stroke [7], a 1.5-fold risk of cognitive impairment or dementia [8], a 1.5-fold risk of Myocardial Infarction (MI) [9], a 2-fold risk of sudden cardiac death [10], a 5-fold risk of Heart Failure (HF) [7], a 1.6-fold risk of Chronic Kidney Disease (CKD) [7], and a 1.3-fold risk of Peripheral Artery Disease (PAD) [7].