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Background: Cardiac resynchronization therapy has become a ratified and established therapy for heart failure to reduce both the morbidity and mortality of the condition, but with a high rate of non-responders which rises up to 30%. In the majority of patients transvenous CRT device placement is preformed, however in some cases mini-thoracotomy is employed as an alternative approach. In this study we followed up and compared patients with CRT devices placed by the transvenous or mini-thoracotomy approach.Methods: Following current CRT guidelines criteria patients were selected and further qualified for device implantation based on the presence of markers of intraventricular (the septal flash) and/or atrio- and/or inter-ventricular dyssynchrony.Based on the CRT device implantation approach, patients were divided in two groups: 18 patients implanted transvenously (VENOUS: 9F/9M, 59±10 years) and 15 patients implanted via mini-thoracotomy (MINI: 6F/9M, 55±14 years). In the second group, echocardiographically guided LV lead placement was performed, seeking for the optimal lead position. Echocardiographic assesment including Doppler myocardial imaging was preformed pre-CRT implantation as well as 6-months after the procedure. Furthermore, echo guided CRT optimization was preformed in the second month post-implantation. Clinical response was defined as a reduction in NYHA class >1, while a reduction of LV end-systolic volume (LVESV) ≥10% defined volume response.Results: Clinical response was noted in all patients at 6-months follow-up. Echocardiographic data reveled volume response in all MINI patients, which was absent in 33% of the VENOUS group and in 24% of overall patients. A significant reduction in LVESV was measured in the MINI group (MINI pre/post: 202/139 ml, p=0.01; VENOUS pre/post: 226/189 ml, p=NS). The average change in LVESV was 18% and 33% in the VENOUS and MINI groups, respectively. In both groups EF increased significantly (MINI pre/post: 21/35%, p<0.0005; VENOUS pre/post: 23/29%, p=0.03).Conclusion: In our study group, clinical response was noted in all patients while volume response was considerably superior after CRT implantation via mini-thoracotomy. Notably, the overall rate of non-responders was smaller compared to previous studies. Thus, a detailed preoperative assessment of CRT candidates should lead to a better response rate. With the shortcomings of a more invasive approach, mini thoracotomy CRT implantation with selective LV lead placement provides significantly better LV reverse remodelling compared to the standard venous approach.