The zebrafish (Dario rerio) has proven to be an excellent animal model for biological research owing to its small size, low cost for maintenance, short generation time, amenable genetics, and optical transparency. Zebrafish have been extensively used in cardiovascular studies in which mutant lines with cardiovascular defects were introduced and analyzed. Despite the small size, technological advances have paved the way to effectively assess cardiac functions of zebrafish. Here, we present a novel art for long-term simultaneous monitoring and analysis of electrocardiogram (ECG) in multiple zebrafish with controlled environment. The system helps minimize the effect of anesthetic drug and temperature to cardiac rhythm side effects as well as save time and efforts by 40-50 fold compared with the conventional approach. We further employed the system to study the Na+ sensitivity in the development of sinus arrest in Tg(SCN5A-D1275N) fish, a study model of the sick sinus syndrome, as well as the relationship between this variant and drug administration. The novel ECG system developed in this study holds promise to greatly accelerate other cardiovascular studies and drug screening using zebrafish.