In this paper, a novel framework to investigate the effect of external electrical signals on cardiac rhythm dynamics using the extended state observer-based control (ESOBC) is proposed. Heterogeneous coupled oscillator model (HCOM) is adopted for the generation of P, Ta, QRS, and T waves, and the realistic synthetic electrocardiogram (ECG) due to its capacity for simulating cardiac muscles response. Sinoatrial (SA) and atrioventricular (AV) nodes and His–Purkinje system are described by modified Van der Pol-type (MVDP) equations connected with time-delay velocity coupling. The electrical responses resulted from depolarization (De) and repolarization (Re) of cardiac muscles are separately presented by modified FitzHugh–Nagumo (MFHN) model. The SA and HP pacemakers are coupled with atrial (AT) and ventricles (VT) muscles, respectively, through the stimulation currents. To satisfy the integral chain form of ESO, and deal with the complex structure of the model, including the large number of parameters, and the coupling between the oscillators and interdependent states, three steps are considered. Firstly, a coordinate transformation is proposed for AT and VT responses described by MFHN model to handle mismatched condition. Following this, the nonlinearity of MFHN and the coupling between cardiac muscles and pacemakers are considered as lumped disturbances. Lastly, an extended state observer is designed to compensate the nonlinearity and estimate the unmeasured system states and handle the lumped disturbances. The stability of the closed-loop system is proved, and the effectiveness of the proposed framework for suppressing well-known rhythm disorder, i.e., sinus tachycardia is demonstrated. The framework presented in this work can be easily extended for a wide range of arrhythmia, and serve as an approach to investigate the effect of external stimulation to the heart muscles.