NOX4 and heart failure: It is also noteworthy that NOX2 and NOX4 contribute to atrial oxidative stress and susceptibility to atrial fibrillation [54,105,106,107,108,109,110,111,112], a comorbidity that is present in roughly one third of patients with HFpEF that can result in chronic arrhythmogenicity that precipitates the progression of cardiac failure [113,114,115,116,117].