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Furthermore, the importance of ‘any myocardial infarction’ as an endpoint is complicated by a debate over the prognostic importance of procedural infarctions as well as how various MI definitions affect the prediction of long-term outcomes735,736 A more recent meta-analysis of RCTs that included the longest available follow-up showed that adding revascularization to GDMT reduced cardiac mortality compared with GDMT alone. The cardiac survival benefit improved with the duration of follow-up and was linearly related to a lower rate of spontaneous MI.55 In ISCHEMIA, patients randomized to initial medical therapy alone had significantly more spontaneous MIs during the 5-year follow-up, which were associated with subsequent cardiovascular death.737 An early invasive strategy was associated with lower long-term risks of cardiovascular events, mainly spontaneous MIs, compared with a conservative strategy, at the cost of a higher risk of procedural MIs.738 Extended follow-up of the ISCHEMIA trial population up to 7 years (ISCHEMIA-EXTEND) revealed a significant 2.2% absolute decrease in cardiovascular mortality (adjusted HR 0.78; 95% CI, 0.63–0.96) favouring the initial invasive strategy.56 The benefit was most marked in patients with multivessel CAD (≥70% diameter stenosis on CCTA; adjusted HR 0.68; 95% CI, 0.48–0.97) but was offset by a significant 1.2% absolute increase in non-cardiac mortality, without a significant difference (absolute decrease of −0.7%) in all-cause mortality.56 In a recent meta-analysis of 18 trials, on the other hand, non-cardiac mortality did not differ significantly by initial invasive or conservative strategy in CCS patients with preserved or slightly impaired LVEF.739 In a post hoc analysis of the ISCHEMIA trial, CAD severity was associated with a higher risk of all-cause death, MI, and the primary endpoint of the trial.317 This effect appeared to be most noticeable in patients with multivessel disease and/or proximal LAD stenosis (≥70% diameter stenosis on CCTA).

4.4.2 Additional considerations on reduced systolic

left ventricular function: myocardial viability, revascularization, and its modality Ischaemic cardiomyopathy is the leading cause of HFrEF, and new ischaemic events are the main drivers of worsening LV function, strongly impacting long-term survival.740 Ischaemic HFrEF is characterized by irreversibly damaged and scarred myocardium alternating with ‘viable’ myocardium that may be dysfunctional owing to repetitive ischaemic episodes (stunning) or chronic hypoperfusion (hibernation).741 According to classical concepts, revascularization combined with GDMT synergistically improves systolic LV function and overall prognosis in patients with ischaemic HFrEF by restoring sufficient perfusion to dysfunctional yet viable myocardial segments and preventing new ischaemic events.742 However, it carries increased periprocedural risk, especially in patients with severe LV dysfunction (LVEF ≤ 35%). A meta-analysis of 26 observational studies, including 4119 patients, showed that CABG can be performed with acceptable operative mortality (5.4%; 95% CI, 4.5%–6.4%) and 5-year actuarial survival (75%) in patients with severe LV dysfunction (mean pre-operative EF of 24.7%).743 In the 1990s, observational studies reported improved survival after revascularization in patients with severe CAD, significant LV dysfunction, and evidence of myocardial viability on imaging tests.744 The PARR-2 trial (PET and Recovery Following Revascularization) randomized 430 patients with suspected ischaemic cardiomyopathy to an F-18-fluorodeoxyglucose PET-assisted strategy or standard care. While there was a non-significant trend towards lower risk of cardiac events at 1 year with PET assistance,745 the 5-year follow-up showed no overall reduction in cardiac events.746 However, significant benefits were observed when adhering to PET recommendations (after excluding 25% protocol violations).746 Post hoc analyses and substudies confirmed the positive outcomes of a PET-guided strategy.747,748

The Surgical Treatment for Ischemic Heart Failure (STICH) trial randomized 1212 patients with CAD without left main diseases eligible for CABG and LVEF ≤35% to receive either CABG and GDMT, or GDMT alone. The trial failed to achieve its primary endpoint of all-cause mortality at a median follow-up of 4 years (HR with CABG, 0.86; 95% CI, 0.72–1.04; P = .12).53 However, at a median follow-up of 9.8 years, both all-cause and cardiovascular mortality were significantly reduced with CABG compared with GDMT alone (from 66.1% to 58.9%; HR 0.84; 95% CI, 0.73–0.97; P = .02; and from 49.3% to 40.5%; HR 0.79; 95% CI, 0.66–0.93; P = .006, respectively).54 The reduction of cardiovascular mortality by CABG was greater in patients with three-vessel disease54 and the reduction of all-cause mortality was greater in younger patients, in whom cardiovascular deaths accounted for a larger proportion of deaths vs. older patients (P = .004 for interaction).749 Viability was assessed by SPECT, dobutamine echocardiography, or both in 50% of STICH patients (298 randomized to CABG and 303 randomized to GDMT alone).750 There were no significant interactions between presence or absence of myocardial viability and improved LV function or long-term survival benefit for CABG above GDMT.747,748,750 There have been no RCTs directly comparing CABG and PCI in patients with ischaemic HF. A meta-analysis of 21 studies, mostly observational except three including STICH, published between 1983 and 2016, supported CABG and PCI on a background of GDMT in appropriate patients with multivessel disease and LV systolic dysfunction; revascularization with either CABG or PCI improved long-term survival compared with GDMT, but compared with PCI, CABG provided a survival benefit and a lower risk of MI or repeat revascularization, with a slightly higher incidence of stroke.751 PCI is increasingly used over CABG for treating patients with ischaemic HF and multivessel disease, as shown by two large registries.752,753 While these registries suggest that CABG is associated with a lower risk of longterm all-cause and cardiovascular mortality and lower MACE compared with PCI in patients with CAD and LVEF ≤35%,752,753 it is important to interpret these observational studies with great caution, given significant differences in baseline characteristics, including age, history of previous MI, severity of CAD, and completeness of revascularization.754 For the comparison of CABG with PCI in managing ischaemic HF with severely impaired LV dysfunction and multivessel CAD, the results of ongoing trials (NCT05427370 and NCT05329285) are awaited. The Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction (REVIVED-BCIS2) trial randomized 700 patients with impaired LV function (EF ≤ 35%), extensive CAD amenable to PCI, and evidence of myocardial viability in at least four dysfunctional myocardial segments to a strategy of PCI plus GDMT or GDMT alone.729 After a 3.4-year follow-up, PCI showed no significant reduction in the composite primary endpoint of all-cause death or HF rehospitalization (HR 0.99; 95% CI, 0.78–1.27; P = .96). Patients treated by PCI showed slight and temporary improvements in their symptoms and no incremental improvement of overall LV function compared with GDMT. A pre-specified secondary analysis of REVIVED-BCIS2, conducted in 87% of patients, failed to establish significant correlations between viability extent (assessed by CMR or dobutamine stress echocardiography) and outcomes, thereby challenging the traditional concept of myocardial hibernation, which can be reversed by revascularization.755 However, the analysis did find that larger amounts of non-viable myocardium were linked to an increased risk of the primary outcome, Downloaded from academic.oup.com/eurheartj/article/45/36/3415/7743115 by guest on 07 October 2026