TNNI3 and heart failure: In the heart, the positive inotropic effect of β-adrenergic signaling is accompanied by reduced myofilament Ca2+ sensitivity via PKA phosphorylation of cTnI (Ser23/24) (Zhang et al. 1995; Kentish et al. 2001). β-Adrenergic receptor antagonists (β-blockers) have been used for decades to treat a variety of cardiac diseases, including hypertension, heart failure, cardiac arrhythmias, and myocardial infarction.