Ventricular arrhythmias and contractile dysfunction are the main causes of death in human heart failure (HF). In a rabbit HF model reproducing these same aspects of human HF, we demonstrate that a 2-fold functional upregulation of Na+-Ca2+ exchange (NaCaX) unloads sarcoplasmic reticulum (SR) Ca2+ stores, reducing Ca2+ transients and contractile function. Whereas β-adrenergic receptors (β-ARs) are progressively downregulated in HF, residual β-AR responsiveness at this critical HF stage allows SR Ca2+ load to increase, causing spontaneous SR Ca2+ release and transient inward current carried by NaCaX. A given Ca2+ release produces greater arrhythmogenic inward current in HF (as a result of NaCaX upregulation), and ≈50% less Ca2+ release is required to trigger an action potential in HF. The inward rectifier potassium current (IK1 is reduced by 49% in HF, and this allows greater depolarization for a given NaCaX current. Partially blocking IK1 in control cells with barium mimics the greater depolarization for a given current injection seen in HF. Thus, we present data to support a novel paradigm in which changes in NaCaX and IK1, and residual β-AR responsiveness, conspire to greatly increase the propensity for triggered arrhythmias in HF. In addition, NaCaX upregulation appears to be a critical link between contractile dysfunction and arrhythmogenesis.