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Both GDMT and CRT can reduce SMR severity. However, GDMT may not be tolerated in patients with HFrEF who develop hypotension and worsening kidney function following uptitration. On the other hand, a successful M-TEER can increase forward stroke volume and blood pressure and improve kidney perfusion so that GDMT may be better tolerated after rather than before this procedure. Thus, similarly to CRT, M-TEER may serve as enabling therapy for GDMT. Notably, catheter ablation for atrial fibrillation and coronary revascularization may have a role in very selected patients. Furthermore, these patients with HFrEF and SMR remain at high risk of clinical events even after successful transcatheter treatments (i.e. M-TEER). Careful follow-up and continuous implementation of GDMT remain a major priority both before and after any intervention. The aim of this state-of-the-art review is to summarize current knowledge about management of HFrEF and ventricular SMR including the entire patient pathway (i.e. diagnosis, treatment and follow-up) with a focus on the effects of GDMT and CRT on SMR as well as on the effects of successful M-TEER on GDMT tolerability.<\/jats:p>","DOI":"10.1093\/eurheartj\/ehaf480","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T07:54:44Z","timestamp":1750319684000},"page":"1294-1303","source":"Crossref","is-referenced-by-count":9,"title":["Heart failure with reduced ejection fraction and ventricular secondary mitral regurgitation: a holistic approach"],"prefix":"10.1093","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3855-1815","authenticated-orcid":false,"given":"Marianna","family":"Adamo","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, Cardiology and Cardiac 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