Abstract: Objective To evaluate the efficacy, safety of cardiac resynchronization therapy (CRT) with atrial septal or ventricular septal puncture implanted into the left ventricular endocardial electrode. Methods A retrospective analysis of 6 heart failure patients with coronary venous malformation or CRT nonresponse diagnosed at the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China from August 2014 to October 2018, with left ventricular endocardial electrodes implanted through atrial septal or ventricular septal puncture. Among them, 4 patients underwent atrial septal puncture and 2 patients' ventricular septal puncture. The QRS width was got before and after operation, and left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left atrial anterior and posterior diameter (LAD) and cardiac function grading were measured, and parameters of left ventricular electrode(threshold, impedance) were measured after 3, 6, 12 and 24 months. Results Six patients underwent successful implantation of left ventricular endocardial electrodes through atrial septal or ventricular septal puncture. There were no serious complications during operation. The QRS width was significantly narrower than before. LVEF was significantly increased and LVEDD was significantly reduced within 24 months; LVESD and LAD were unchanged, and parameters of left ventricular electrodes (threshold, impedance) were relatively stable, no obvious abnormal events such as diaphragmatic stimulation, thromboembolism, hemorrhage and ventricular arrhythmia, and the patient's heart function was significantly improved. None was deaths. Conclusion The left ventricular endocardial electrode is successfully inserted through the atrial septal or ventricular septal puncture, and certain clinical efficacy is obtained.