Myocardial viability testing: all STICHed up, or about to be REVIVED?

Matthew Ryan, Holly Morgan, Amedeo Chiribiri, Eike Nagel, John Cleland, Divaka Perera, Matthew Ryan, Holly Morgan, Amedeo Chiribiri, Eike Nagel, John Cleland, Divaka Perera

Abstract

Patients with ischaemic left ventricular dysfunction frequently undergo myocardial viability testing. The historical model presumes that those who have extensive areas of dysfunctional-yet-viable myocardium derive particular benefit from revascularization, whilst those without extensive viability do not. These suppositions rely on the theory of hibernation and are based on data of low quality: taking a dogmatic approach may therefore lead to patients being refused appropriate, prognostically important treatment. Recent data from a sub-study of the randomized STICH trial challenges these historical concepts, as the volume of viable myocardium failed to predict the effectiveness of coronary artery bypass grafting. Should the Heart Team now abandon viability testing, or are new paradigms needed in the way we interpret viability? This state-of-the-art review critically examines the evidence base for viability testing, focusing in particular on the presumed interactions between viability, functional recovery, revascularization and prognosis which underly the traditional model. We consider whether viability should relate solely to dysfunctional myocardium or be considered more broadly and explore wider uses of viability testingoutside of revascularization decision-making. Finally, we look forward to ongoing and future randomized trials, which will shape evidence-based clinical practice in the future.

Keywords: Ischaemic cardiomyopathy; Ischaemic left ventricular dysfunction; Myocardial hibernation; Myocardial viability.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Figures

Graphical Abstract
Graphical Abstract
Evidence for the relationship between viability testing and clinical outcomes. Viability and prognosis: the STICH viability sub-study showed viability had no impact on prognosis after adjustment for baseline variables. Viability and prognostic benefit of revascularization: no association shown in the STICH viability sub-study, however, has been shown in PARR-2 substudy and observational data;  ,   * will be further explored in the ongoing REVIVED trial. Viability and functional recovery: a relationship has been demonstrated for medical therapy. Viability to functional recovery via revascularization—no association shown in randomised controlled trials (RCTs), but extensive observational data. A link between functional recovery and prognosis is suggested from long-term STICH follow-up data. A link between revascularization and prognosis was shown for CABG in the STICH trial (long-term follow-up, not seen in HEART trial).
Figure 1
Figure 1
A conceptual construct for the stages of hibernation. After a short period of ischaemia, which is alleviated before irreversible damage has taken place, contractile dysfunction can persist for hours to days; this is termed stunning. If the cell is exposed to repeated episodes of hypoperfusion, it can enter early- or ‘short-term’ hibernation with metabolic adaptation and early histological changes becoming apparent: at this point, function remains persistently abnormal between episodes of ischaemia, unless the stimulus is withdrawn for an extended period. Over a longer duration, more extensive histological change occurs, some myocytes are lost with fibrotic replacement, whilst others enter advanced hibernation with cellular adaptations and remodelling. Conversely, infarction, usually caused by a single prolonged period of ischaemia, results in complete cellular necrosis and replacement of normal tissue with fibrous scar.
Figure 2
Figure 2
Viability testing. The four key methods used to assess myocardial viability. Single-photon emission computed tomography (SPECT) measures thallium or technetium uptake to assess myocyte membrane integrity; positron emission tomography (PET) measures the uptake of fluorodeoxyglucose as a marker of glucose metabolism; dobutamine stress echocardiography (DSE) using inotropic stimulation to measure contractile reserve and cardiac magnetic resonance (CMR) using late gadolinium enhancement to highlight regions with increased extracellular volume as an indication of infarction.
Figure 3
Figure 3
The STICH viability sub-study: 10-year outcome data.

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