Management of patients with ischaemic cardiomyopathy: is there still a role for ischaemia-guided revascularization? 

This editorial refers to ‘Impact of revascularization guided by functional testing in ischaemic cardiomyopathy’, by E. Ródenas-Alesina et al., https://doi.org/10.1093/ehjci/jeac125.

Ischaemic cardiomyopathy (ICM) is generally defined in the presence of significant left ventricular (LV) systolic dysfunction—i.e. LV ejection fraction (EF) <40%—associating with and related to the presence of significant and diffuse coronary artery disease (CAD) or secondary to an (extensive) acute myocardial infarction (AMI).¹ As a general rule, if compared with patients with non-ICM, patients with ICM have a significantly worse long-term prognosis (≈30% higher mortality at 5-year follow-up according to classical appraisals),² justifying the need for devising dedicated treatment strategies for this high-risk category of subjects. However, patients with ICM have been rarely included in trials on stable CAD, with most of the available evidence on their management coming from a ‘handful’ of prospective randomized studies. Above all, the prognostic benefit of ‘complete’ (surgical) coronary revascularization in ICM comes from the long-term results of ‘The Surgical Treatment for Ischemic Heart Failure (STICH) extension study’, showing significantly lower all-cause [hazard ratio (HR) 0.84; 95% confidence interval (CI), 0.73–0.97; P = 0.02] and cardiovascular mortality (HR 0.79; 95% CI, 0.66–0.93; P = 0.006) in revascularized patients at a median follow-up of 9.8 years.³ However, despite these overall positive results, the predictors of a favourable response to coronary revascularization in patients with ICM are still debated. For example, in STICH, no significant interaction was observed between either the presence or the extent of myocardial viability—evaluated through either single-photon computed tomography (SPECT) or stress echocardiography—and the beneficial effect of coronary revascularization over medical therapy (MT).⁴ Better results in favour of viability-guided revascularization came from the Positron Emission Tomography and Recovery Following Revascularisation (PARR-2 trial), also enrolling patients with ICM, in whom a management adherent to fluorodeoxyglucose-positron emission tomography results led to a lower event rate (≈27% relative risk reduction at 5-year follow-up, although largely guided by a significantly lower rehospitalization rate), particularly in the presence of extensive hibernating myocardium (>7% of the LV).^5,6 Due to these conflicting results, the operative role of viability assessment in patients with ICM is still a matter of debate.⁷ On the contrary, the presence of a large area of LV-inducible ischaemia (i.e. encompassing >10% of the LV) still represents a Class I indication for coronary revascularization in patients with CAD, independent of the degree of the underlying LV functional impairment.⁸ However, as in patients with CAD at large, the evidence in favour of ischaemia-guided revascularization in the setting of ICM is still quite insecure. In this regard, classical data from Hachamovitch et al.,⁹ including retrospective data from >13k patients submitted to SPECT imaging, did not support any significant prognostic relevance of inducible myocardial ischaemia in patients with myocardial scar involving >10% of the LV myocardium, a condition that is typically encountered in patients with ICM. On the same lines, a recent dedicated subanalysis of the STICH trial seemed to exclude any beneficial impact of ischaemia-guided coronary revascularization in patients with ICM.¹⁰ These results are at odds with recent data emanating from a subanalysis of the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial, possibly suggesting a benefit of revascularization in patients with heart failure (HF) and a moderately depressed LVEF (35–45%),¹¹ placing new emphasis on dedicated studies evaluating the role of ischaemia-guided revascularization in ICM.

Ródenas-Alesina et al.¹² evaluated retrospectively whether the presence and burden of inducible myocardial ischaemia—as evaluated by SPECT myocardial perfusion imaging (MPI) on a conventional camera—had an appreciable effect on the possible prognostic impact of early coronary revascularization (ECR; within 6 months from enrolment) in patients with ICM. Among the entire cohort of >12k patients submitted to MPI between 2010 and 2018 in a single institution, a final population of 109 patients with ICM undergoing ECR was compared with the same number of subjects not receiving ECR, selected through propensity score matching that considered major clinical, functional, and imaging variables. The final population consisted almost exclusively of male subjects (89%) with a mean age of 67.2 years (±10.5), most of whom having a history of AMI (61%). On imaging, the mean LVEF was 31.5% (±6.7), with roughly half of the patients showing significant inducible ischaemia on MPI (>10% of the LV), while 39% had evidence of ‘extensive’ fixed perfusion defects (involving more than three myocardial segments). Percutaneous coronary revascularization was performed in the outmost majority of patients, with only 10% of them undergoing coronary artery bypass graft. During a median follow-up of 4.1 years, 102 patients experienced a major adverse cardiac event (MACE), involving either cardiovascular death, non-fatal AMI, or HF hospitalization. The main result of the study was that a significant prognostic interaction existed between the presence of significant inducible ischaemia and ECR (P for interaction = 0.22), so that revascularization of patients with >10% LV ischaemia was associated with a lower event rate than initial MT (HR 0.59, 95% CI, 0.30–1.18; P = 0.13), while the opposite seemed true in the presence of a more limited ischaemic burden (<10% of the LV; HR 1.67, 95% CI, 0.94–2.96; P = 0.08). Of note, the risk of MACE in patients with >10% of ischaemia submitted to ECR was similar to that observed in patients with <10% of ischaemia and no ECR. While the authors should be commended for their attempt of providing evidence in favour of ischaemia-guided revascularization in a relevant clinical scenario such as ICM, a number of limitations of the study should also be acknowledged. The retrospective nature of the study, coupled with the limited patient population, makes the conclusions only hypothesis-generating. Moreover, the lack of a systematic assessment of myocardial viability and the absence of any information on the impact of ECM on LV function at follow-up—a parameter whose prognostic relevance has been reinforced by recent appraisals¹³—point to the need for dedicated well-powered prospective studies further evaluating the role of imaging-guided management of patients with ICM. Similarly, no information on the completeness of revascularization is provided, nor on the MT prescribed, an aspect of considerable relevance, given the tremendous improvements in HF treatments that have been witnessed lately. Despite these limitations, studies such as those of Ródenas-Alesina et al.¹² breathe new life into the role of ischaemia assessment in patients with CAD at large, a highly relevant topic after the release of the main results of the ISCHEMIA trial that somewhat downplayed the impact of ischaemia-guided management in this category of patients.¹⁴ In this respect, quite recent evidence seems to support ‘again’ the benefit of revascularizing ischaemic myocardium, provided that a ‘severe’ burden of ischaemia is present (i.e. >15% of the LV more than the usual 10%),¹⁵ possibly pointing to the need for ‘hardening’ current indications for coronary revascularization. Moreover, the results provided by Ródenas-Alesina et al. are also in line with evidence supporting the prognostic benefit of ‘management appropriateness’ in patients with stable CAD, with targeted (complete) coronary revascularization in the presence of ischaemia-causing lesions and MT only otherwise.¹⁶ In fact, in the study by Ródenas-Alesina et al.,¹² the group of patients with the worst prognosis seemed to be represented by those in whom ECR was performed despite the absence of significant ischaemia,¹² as a possible sign of the deleterious effect of ‘inappropriate’ coronary revascularization.

Taken together, present and previous results may revive the role of ischaemia-guided revascularization in patients with ICM, suggesting how a careful selection of patients—centred on an accurate quantification of the ischaemic burden—might individuate those who could benefit from an early treatment aiming at the complete revascularization of all haemodynamically significant coronary lesions.

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Author notes