Heart failure was a major risk factors for secondary sinus node dysfunction, the mechanism of which may be related to gene mutation in HCN4, a Na + /K + hyperpolarization-activated cyclic nucleotide-gated (HCN) channels that was a molecular marker of functional sinus node cell activity and played a key role in the pacemaker potential (38, 39). The gene discussed is HCN4; the disease is heart failure.