Background/Objectives: Heart failure (HF) with reduced ejection fraction (EF) has, in more than 50% of cases, an ischemic etiology and continues to be associated with increased mortality and morbidity despite all the progress registered in the field of medical therapy and interventional revascularization. Myocardial revascularization is extensively used in clinical practice based on the traditional concept that it can improve myocardial function and outcome in ischemic HF. This review is aimed at presenting current knowledge regarding revascularization in patients with chronic ischemic HF and reduced EF. Methods: The impact of revascularization on symptomatology, left ventricle reverse remodeling, major adverse cardiac events (MACEs), and the role of complete revascularization and of percutaneous interventional revascularization in chronic total occlusion (PCI-CTO) were analyzed. The best therapeutic strategies, revascularization and/or optimal medical therapy (OMT), are debated in different categories of patients, in order to identify who will benefit more from revascularization strategies. Results: Based on the long-term results of the STICH trial incorporated in the guidelines with a class I-b recommendation, coronary artery bypass graft (CABG) remains the main modality of revascularization for prognostic improvement in ischemic HF with multivessel disease. But real-life patients are usually old with multiple comorbidities and high surgical risk. In this category, the Heart Team opinion is required to evaluate the probability of complete revascularization and to choose between percutaneous coronary intervention (PCI) and CABG according to clinical status and coronary anatomy. Conclusions: However, until further studies are available, the results of the REVIVED-BCIS2 trial encourage OMT over PCI in patients with ischemic cardiomyopathy. The available randomized controlled trials (RCTs) showed improved angina and quality of life in PCI-CTO versus OMT, but the effect on MACEs was not demonstrated.

Non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) often coexists with multivessel coronary artery disease (MVD), complicating treatment decisions. Current guidelines suggest complete revascularization (CR), yet robust evidence in hemodynamically stable patients remains insufficient. However, the comparative benefit of CR over incomplete revascularization (IR) in reducing ischemic events and improving cardiac function in this population is not well established. The aim of this study was to evaluate the impact of CR on all-cause mortality, cardiac death, and ischemic readmissions at 6 and 12 months, as the composite primary outcome, and to assess left ventricular ejection fraction (LVEF) improvement at discharge and hospital length of stay, as secondary outcomes. A total of 282 hemodynamically stable NSTE-ACS patients with MVD were included, of whom 218 (77.3%) underwent CR and 64 (22.7%) IR. The primary composite outcome occurred in 40.6% of IR patients versus 11.0% in the CR group at 6 months (p < 0.001), and 68.8% vs. 22.0% at 12 months (p < 0.001). CR was associated with significantly lower rates of all-cause and cardiac death, myocardial infarction, and unstable angina. Stroke incidence was similar. Event-free survival favored CR. Multivariable analysis identified CR and baseline LVEF as independent predictors of 12-month outcomes (HR for CR: 7.797; 95% CI: 3.961–15.348; p < 0.001; HR for LVEF: 0.959; CI: 0.926–0.994; p = 0.021). These findings strongly support CR as the preferred therapeutic strategy. Future prospective randomized studies are warranted to confirm the results.

Non-ST-segment elevation myocardial infarction (NSTEMI) has become the predominant form of acute coronary syndrome (ACS) and is frequently associated with multivessel coronary artery disease (MVD). Patients presenting with NSTEMI and MVD represent a particularly high-risk population characterized by advanced age, comorbidities, and an increased atherosclerotic burden. Although advances in pharmacological therapy and early invasive management have improved prognosis, the optimal revascularization strategy in this setting remains uncertain. In contrast to ST-segment elevation myocardial infarction (STEMI), where randomized controlled trials consistently support complete revascularization, evidence in NSTEMI with MVD is limited and is largely derived from observational studies and registry data. This has generated ongoing debate regarding whether complete revascularization offers superior outcomes compared with culprit-only percutaneous coronary intervention (PCI), and whether non-culprit lesions should be treated during the index procedure (immediate strategy) or in a staged manner. Current data suggest that complete PCI is generally associated with reduced recurrent ischemia, reinfarction, and repeat revascularization, with potential long-term survival benefits. However, patient comorbidities, lesion complexity, and procedural risk continue to influence outcomes, highlighting the importance of individualized decision-making. This narrative review synthesizes contemporary evidence on PCI-based revascularization strategies in NSTEMI with MVD, focusing on two central aspects: the extent of revascularization (complete versus incomplete) and the timing of intervention (single-stage versus staged). By integrating findings from registries, randomized trials and guideline recommendations, the review identifies areas of consensus, persisting uncertainties, and key evidence gaps. Ultimately, it underscores the need for large, dedicated trials to guide practice and optimize outcomes for NSTEMI patients with multivessel coronary disease.