State of the Art: Imaging for Myocardial Viability — AHA Scientific Statement

Authors, Journal, Affiliations, Type, DOI

• Garcia MJ (Montefiore/Albert Einstein), Kwong RY (Brigham and Women's), Scherrer-Crosbie M (Penn), Taub CC (Montefiore), Blankstein R (Brigham and Women's), Lima J (Johns Hopkins), Bonow RO (Northwestern), Eshtehardi P (Emory), Bois JP (Mayo Clinic)
• Circulation: Cardiovascular Imaging. 2020;13:e000053
• On behalf of the AHA Council on Cardiovascular Radiology and Intervention and Council on Clinical Cardiology; endorsed by the Society for Cardiovascular Magnetic Resonance
• Review / AHA Scientific Statement
• DOI: 10.1161/HCI.0000000000000053

Overview

This 2020 AHA Scientific Statement provides a comprehensive, modality-by-modality review of imaging tools for myocardial viability in ischemic cardiomyopathy. Despite the pathophysiological logic that identifying hibernating or stunned myocardium should guide coronary revascularization, the landmark STICH and PARR-2 randomised trials failed to demonstrate a survival benefit from viability-guided CABG over guideline-directed medical therapy. The document compiles comparative diagnostic performance data, presents clinical decision algorithms for chronic and subacute ischemic LV dysfunction, and argues that viability imaging retains a role in complex individual patient management even in the absence of definitive outcome-level evidence.

Keywords

AHA Scientific Statements; echocardiography, stress; fractional flow reserve, myocardial; hibernation; magnetic resonance imaging; myocardial perfusion imaging; myocardial stunning

Key Takeaways

Pathophysiology of Myocardial Viability

• Scope of ischemic heart disease: >110 million individuals affected worldwide; up to one-third of acute MI patients develop heart failure.
• Clinical definition of viability: Dysfunctional myocardium at rest with potential for functional recovery on restoration of normal blood supply — the clinically actionable definition distinct from cellular-level viability.
• Stunning: Decreased contractile function from transient hypoperfusion episodes with normal or near-normal resting flow; coronary flow reserve (CFR) is reduced. Repetitive stunning leads to cardiomyocyte structural changes: loss of sarcomeres, sarcoplasmic reticulum, and T-tubules; increased glycogen plaques.
• Hibernation: Originally conceived as adaptive downregulation of contractile function during sustained reduced resting flow. Experimental data now suggest hibernation may be a consequence of repetitive stunning (contractile dysfunction → reduced resting flow), not its cause. Both states share reduced CFR, impaired calcium handling, and reduced sarcoplasmic reticulum sensitivity.
• Continuum: Stunned → hibernating myocardium is a spectrum; structural changes eventually become irreversible, resulting in ischemic cardiomyopathy.
• SCD substrate: Extent of myocardial scar predicts LV remodeling and SCD risk; hibernating myocardium also creates a substrate for ventricular tachyarrhythmias.

Molecular and Histological Imaging

• Under ischemia, myocardial metabolism switches from beta-oxidation of fatty acids to glucose oxidation; glucose transporter 1 is upregulated. [18F]-FDG PET detects this metabolic switch as increased tracer uptake in viable tissue.
• Additional PET tracers: [11C]-palmitate (fatty acid metabolism), [11C]-acetate (myocardial oxygen consumption).
• CMR with gadolinium detects expanded extracellular space in infarcted/fibrotic myocardium via T1-weighted late gadolinium enhancement (LGE).

Echocardiography

• Resting wall thickness: LV end-diastolic wall thickness (EDWT) <6 mm was historically thought to exclude relevant viability. Shah et al. (JAMA 2013) challenged this: ~20% of thinned segments without LGE demonstrated function improvement after revascularization — wall thinning alone is insufficient to exclude viability.
• Dobutamine stress echocardiography (DSE): Low-dose dobutamine (2.5–10 µg/kg/min) increases contractility in viable myocardium. Continued infusion produces a biphasic response (initial improvement then deterioration at high dose) = pathognomonic for hibernating viable myocardium. Sensitivity 76%, specificity 81% for predicting post-revascularization recovery.
• Sustained contractile improvement during graded dobutamine also indicates viable ischemic myocardium but can be a normal response in non-ischemic DCM.
• Contrast echo perfusion: Highly sensitive but less specific than DSE for viability; use remains off-label; high inter- and intra-observer variability.
• Speckle tracking (STE): Layer-specific analysis can predict LV functional recovery and remodeling after acute MI; diagnostic accuracy similar to LGE-CMR in preliminary studies.
• LV remodeling: LV end-systolic volume >130 mL is associated with 38% higher cardiac events at 3 years after revascularization despite metabolic evidence of viability — extensive remodeling attenuates the functional benefit of revascularization.

Nuclear Scintigraphy

• Thallium-201 (201Tl): Potassium analog actively transported into viable myocytes via Na+/K+-ATPase; intact cell membrane required. Key property: redistribution (initial fixed defect improves on delayed imaging). Rest-redistribution protocol: ≥10% uptake increase in resting defect = viable. Sensitivity 87%, specificity 54%.
• 99mTc-sestamibi/tetrofosmin: Passive diffusion; no redistribution. Similar accuracy to 201Tl (both Class I agents) but better imaging characteristics (higher photon energy, lower radiation dose).
• PET [18F]-FDG viability study (gold standard metabolic imaging):
  • Three patterns: (1) hibernating myocardium = reduced perfusion + preserved FDG uptake (mismatch); (2) transmural scar = absent perfusion + absent FDG; (3) non-transmural scar = partially reduced perfusion + concordant FDG reduction.
  • PET-FDG has highest sensitivity (92%) among nuclear methods.
  • Patient preparation: 6-hour fast + oral glucose load (25–50 g) ± insulin to promote myocardial glucose uptake.
  • 25–30% of myocardial segments must demonstrate dysfunction and viability to achieve significant global LVEF improvement after revascularization.

CMR Imaging

• CMR characterizes hibernating myocardium via three complementary techniques: (1) LV EDWT, (2) inotropic reserve with low-dose dobutamine, and (3) transmural extent of LGE.
• LGE transmural extent — functional recovery prediction (Kim et al., NEJM 2000, n=50):
  • Akinetic segments with no or minimal subendocardial infarction: >90% probability of contractile recovery after successful revascularization.
  • 1–25% transmural LGE: high probability of recovery.
  • 26–75% transmural LGE: intermediate; benefits from combined LGE + dobutamine reserve assessment.

  • 50% transmural LGE: <10% probability of contractile recovery despite successful revascularization.

  • The stepwise relationship between transmural extent and recovery probability is the diagnostic backbone of CMR viability assessment.
• LGE sensitivity vs dobutamine CMR specificity: LGE-CMR has highest sensitivity (95%) for predicting segmental recovery; dobutamine CMR has highest specificity (91%) for ruling out non-viability. LGE has higher NPV (90%); dobutamine CMR has higher PPV (93%).
• Combined approach (meta-analysis, 24 CMR studies, Romero et al. 2012): LGE + dobutamine reserve complementary; combination improves overall accuracy.
• EDWT limitation: 5.5 mm EDWT cutoff: 94% sensitivity but only 52% specificity for functional recovery — wall thinning alone is insufficient.
• Dark-blood LGE technique: Increasingly used, especially at experienced centres, to improve detection of subendocardial MI where bright-blood LGE may miss thin layers of infarction due to suboptimal blood-to-scar contrast.

Cardiac Computed Tomography

• Contrast-enhanced multidetector CT can detect myocardial hyperenhancement and index extracellular volume expansion (replacement fibrosis), validated against histopathology.
• Key differences from CMR: CT contrast agent has smaller molecular size → optimal imaging at ~5 minutes (vs 10–15 minutes for CMR); direct x-ray attenuation effect rather than indirect T1 shortening.
• Major limitation: Lower contrast-to-noise ratio than LGE-CMR; emerging multi-energy CT systems may improve iodine mapping.

Modality Comparative Studies

Data from Romero et al. 2012 and Schinkel et al. 2007. Pooled data from 3034 patients in 105 studies.

• All modalities predict similar degree of LVEF improvement after revascularization (8–10% absolute), regardless of imaging method.
• Modalities interrogate different physiological surrogates (blood flow, metabolism, contractile reserve, extracellular volume) — results can be conflicting or complementary; no single dichotomized test captures the full complexity.

Clinical Scenarios

• Proposed algorithm (chronic ischemic LV dysfunction): Assess symptom status → if no angina, perform viability imaging → weigh revascularization probability, extent of remodeling, and surgical risk alongside imaging findings (Figure 11).
• Proposed algorithm (subacute ischemic LV dysfunction): Similar framework with consideration that early post-MI stunning confounds viability interpretation; 201Tl redistribution useful to document stunned but viable territory justifying revascularization risk (Figure 12).
• Clinical case examples illustrate intermediate transmural LGE (25–50%) + preserved metabolic activity on 201Tl → justifying PCI; large fixed 201Tl defect → recommending optimal medical therapy.

Lessons from Recent Clinical Trials

• STICH trial (10-year results, NEJM 2011/2019, n=1212, LVEF ≤35%): CABG + GDMT improved long-term all-cause and CV mortality vs GDMT alone — confirming survival benefit of surgical revascularization in ischemic cardiomyopathy. However, 30-day CABG mortality was higher.
• STICH viability substudy (n=618): Viability by SPECT or dobutamine echo defined by prespecified binary thresholds: patients with viable myocardium had lower 5-year mortality (33% vs 50%), but viability status did NOT discriminate patients who benefited from CABG vs GDMT. No significant interaction between viability and treatment arm for mortality, CV mortality, or composite endpoints.
• STICH interpretation: Improved GDMT adherence (especially beta-blockers) in the modern era may explain why the incremental benefit of revascularization guided by viability imaging over GDMT alone was eliminated. LVEF increased to a similar degree in GDMT-only and CABG patients with viable myocardium; 10-year survival was not related to whether LVEF increased.
• PARR-2 trial (n unspecified, PET-guided): Patients randomised to PET viability imaging did NOT demonstrate improved survival after revascularization vs standard care. Post-hoc analysis suggested benefit only when PET guidance was strictly adhered to.
• Orlandini et al. meta-analysis: PET not superior to SPECT or dobutamine echo in predicting survival after revascularization in LV dysfunction.

Future Directions

• Viability testing still argued to have clinical utility: (1) Ischemic cardiomyopathy carries high CV event risk; (2) selected high-risk patients with multivessel CAD + LV dysfunction may benefit from revascularization; (3) functional recovery more likely in viable segments regardless of imaging modality.
• No single viability test expressed dichotomously can fully characterize the physiological complexity of ischemic myocardium and coronary revascularization.
• Future trials should target patients where management decisions are genuinely uncertain; incorporate quantitative, not binary, viability measurements; and assess endpoints beyond LVEF change (functional class, diastolic relaxation, rhythm burden, QoL, polypharmacy reduction).

Limitations of the Document

• STICH and PARR-2 used SPECT and dobutamine echocardiography, not CMR-based viability assessment — whether CMR-guided viability testing would have a different outcome remains unanswered.
• Head-to-head comparisons between modalities are limited by study design heterogeneity (patient enrolment timing, revascularization completeness, follow-up duration).
• LV systolic function recovery as the gold standard is insufficient; patient-centred endpoints (QoL, diastolic function, arrhythmia burden) were not tested.
• Clinical algorithms presented in Figures 11–12 are consensus-based, not clinically validated.
• Quantitative absolute cutoffs (e.g., 25–30% viable segments required for global LVEF benefit) were derived from small historical cohorts.

Key Concepts Mentioned

• concepts/Myocardial-Viability — central concept of the document
• concepts/Late-Gadolinium-Enhancement — transmural extent used for viability stratification

Key Entities Mentioned

• entities/Heart-Failure — ischemic cardiomyopathy context; revascularization decision-making
• entities/Chronic-Coronary-Disease — CAD management background

Wiki Pages Updated

• wiki/sources/imaging-viability-aha-2020.md (created)
• wiki/concepts/Myocardial-Viability.md (created)
• wiki/concepts/Late-Gadolinium-Enhancement.md (updated — viability-specific LGE transmural extent data)
• wiki/entities/Heart-Failure.md (updated — viability imaging subsection in ischemic cardiomyopathy section)
• wiki/wikiindex.md (updated)
• wiki/sourceindex.md (updated)