This thesis addresses a critical challenge in heart failure (HF) management: non-responders to Cardiac Resynchronization Therapy (CRT) often face poor prognoses due to the lack of standardized success criteria. By reviewing updated guidelines, it redefines outdated "responder" and "non-responder" labels, introducing categories like "non-progressors" (who stabilize) and "progressors" (who worsen) for more accurate patient evaluation. The work explores multifactorial causes of inadequate CRT responses, including patient selection, technical factors related to implantation, programming details and device optimisation, CRT optimised by conduction system stimulation, appropriate management of comorbidities and optimisation of drug therapy. It emphasizes a multidisciplinary approach to improve outcomes, such as reducing hospitalizations, mortality rates and improving quality of life for HF patients with reduced ejection fraction.