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Viable: Yes, No, or Somewhere in the Middle?^_*

Division of Cardiovascular Medicine, University of Virginia Health System, Charlottesville, Virginia

Key Words: viability • revascularization • left ventricular dysfunction • PARR-2 • positron emission tomography (PET) • F-18-fluorodeoxyglucose (FDG) • cardiac magnetic resonance (CMR)

In this issue of iJACC, D'Egidio et al. (5) present a post hoc substudy of the PARR-2 trial, looking only at those patients in the parent trial who underwent PET-FDG imaging. They found that increasing amounts of perfusion-metabolism mismatch correlated significantly with increasing benefit from revascularization. Although the composite outcome was driven in large measure by repeat hospital stays for angina and was not powered to look at individual end points such as death or MI, this study does support a growing body of evidence that viability testing is a powerful predictor of cardiovascular outcome after revascularization. The authors in this study also found that worsened kidney function significantly and independently predicted poorer outcomes after revascularization.

One of the contributions of this report is that it illustrates that viability can (and probably should) be viewed as a continuous rather than dichotomous variable. All of the leading imaging modalities used to assess viability (PET-FDG, single-photon emission computed tomography, and cardiac magnetic resonance [CMR]) are able to fairly easily identify viability or the lack thereof at either end of the spectrum. Patients with either clear-cut viability or transmural infarction fairly reliably respond to revascularization as their viability scores would predict, independent of ejection fraction (6). But each modality also has a grey zone where the presence or absence of viability is more difficult to determine and is often decided by a somewhat arbitrary cut point. These cut points are usually statistically derived and lie in the middle of a continuum rather than falling on a natural step-up or step-down of outcomes (7). The treating physicians in the PARR-2 trial who did not follow the PET-FDG–guided recommendations for revascularization most often did so in this middle zone of "moderate viability." What should we do when a patient is in this middle ground? Although viability cut points are necessary for research applications, their clinical benefit is probably more modest. Even if the 7% cutoff found in this trial is validated in future studies, it might not be correct to assume that someone with mismatch close to the cut point will respond in the same way as someone at the far end of the spectrum. It is also difficult to know how to apply cut points to individual patients, many of whom do not reliably respond as their mid-range viability score would predict. Perhaps we need to recognize that the question of viability might not always have a black or white answer. When patients are in this grey zone, other factors affecting their outcome also need to be considered.

Some important factors that need to be taken into account along with a patient's viability results are kidney function, mitral regurgitation, left ventricular end-diastolic volume, and the presence of angina. Poor kidney function has repeatedly been shown to be one of the most potent independent risk factors for mortality after coronary artery bypass grafting (CABG) (8), a finding that was confirmed in the present study (5). The risk of death after revascularization increases incrementally as kidney function worsens (9) and should increase our threshold for intervention accordingly. Adding mitral valve repair or replacement (MVR) to CABG also significantly increases the risk of short- and long-term mortality. Absence of viability in the presence of severe mitral regurgitation portends a poor prognosis after revascularization. It has been shown, however, that the presence of viability is a particularly strong predictor of survival in patients with significant ischemic mitral regurgitation referred for surgical revascularization with consideration of MVR (10,11). Therefore, in this subgroup of patients it might be especially useful to heed the results of viability testing. Another independent predictor of mortality was demonstrated by Santana et al. (12), who showed that increased end-diastolic volume (260 ml) and elevated end-systolic volumes (200 ml) portended poorer event-free survival 2 years after revascularization, independent of PET-FDG mismatch, revealing that a remodeled left ventricle—even in the absence of scar—is less likely to regain function after revascularization. Finally, patients' symptoms should also affect our threshold for intervention. A patient with low-moderate viability but persistent angina despite medical therapy might be a more reasonable candidate for intervention than an asymptomatic patient with a viability score just above the cut point. These and other comorbidities proven to affect revascularization outcomes should inform our decision of whether or not to intervene, especially when viability testing is in the moderate range.

Two valuable imaging modalities used to assess viability include PET-FDG and CMR imaging. PET-FDG offers excellent sensitivity due to its ability to image both perfusion and the metabolic derangements found in ischemic myocardium. Reported positive and negative predictive values and diagnostic accuracy for PET-FDG in predicting functional recovery after revascularization are 86%, 100%, and 90%, respectively (13). In contrast, the spatial and temporal resolution of CMR make it the gold standard for assessing left ventricular function and volumes as well as the presence, size, and transmural extent of scar formation and microvascular obstruction. It has been shown that the transmurality of an infarct seen on delayed gadolinium enhanced images accurately predicts long-term remodeling and improvement in left ventricular function after revascularization (14), with the presence of microvascular obstruction adding additional prognostic value (15). Accuracy is further improved with CMR assessment of functional recovery with low-dose dobutamine, especially in areas of nontransmural infarction (16). Current data suggest that PET-FDG is probably more sensitive and CMR more specific in defining areas of myocardium that are likely to improve with revascularization (13,17). Ongoing improvement of imaging protocols and the development of hybrid imaging modalities such as PET-CMR might serve to reduce the size of the grey zone and improve our ability to predict who will respond well to invasive therapies.

Ongoing studies that will shed further light on this subject include the STICH (Surgical Treatment for Ischemic Heart Failure) trial (18), which has randomized over 1,200 patients with severely decreased left ventricular function to either medical management or bypass surgery, many of whom had viability testing with CMR performed as part of their initial evaluation. Future randomized studies similar to PARR-2 but that take into account physician and patient discretion in cases of moderate viability are needed to conclusively demonstrate that viability testing can lead to improved outcomes.

In summary, viability testing is an extremely useful tool for predicting outcomes after revascularization in patients with ischemic cardiomyopathy. Patients who are in the mid-range of viability will likely benefit from a thoughtful approach taking into account kidney function, symptoms, and other comorbidities to obtain the best possible outcome. Future studies and improved imaging techniques will likely serve to narrow the grey zone and allow for even more accurate predictions of who will benefit from revascularization.

	Footnotes

 
^_* Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.

^_* Reprint requests and correspondence: Dr. George A. Beller, University of Virginia, Private Clinics Building, Room 5593, P.O. Box 800158, Charlottesville, Virginia 22908-0158 (Email: GAB4C{at}hscmail.mcc.virginia.edu).

	REFERENCES

Top REFERENCES

 

1. Allman KC, Shaw L, Hachamovitch R, Udelson J. Myocardial viability testing and impact of revascularization on prognosis in patients with coronary artery disease and left ventricular dysfunction: a meta-analysis J Am Coll Cardiol 2002;39:1151-1158.[Abstract/Free Full Text]
2. Schinkel AFL, Bax JJ, Poldermans D, Elhendy A, Ferrari R, Rahimtoola SH. Hibernating myocardium: diagnosis and patient outcomes Curr Probl Cardiol 2007;32:375-410.[CrossRef][Web of Science][Medline]
3. Bax JJ, Poldermans D, Elhendy A, Boersma E, Rahimtoola SH. Sensitivity, specificity, and predictive accuracies of various noninvasive techniques for detecting hibernating myocardium Curr Probl Cardiol 2001;26:147-186.[Medline]
4. Beanlands R, Nichol G, Huszti E, et al. F-18-Fluorodeoxyglucose positron emission tomography imaging-assisted management of patients with severe left ventricular dysfunction and suspected coronary disease (PARR-2) J Am Coll Cardiol 2007;50:2002-2012.[Abstract/Free Full Text]
5. D'Egidio G, Nichol G, Williams KA, et al. PARR-2 Investigators Increasing benefit from revascularization is associated with increasing amounts of myocardial hibernation: a substudy of the PARR-2 trial J Am Coll Cardiol Img 2009;2:1060-1068.[Abstract/Free Full Text]
6. Pagley PR, Beller GA, Watson DD, Gimple LW, Ragosta M. Improved outcome after coronary bypass surgery in patients with ischemic cardiomyopathy and residual myocardial viability Circulation 1997;96:793-800.[Abstract/Free Full Text]
7. Dilsizian V. Cardiac magnetic resonance versus SPECT: are all noninfarct myocardial regions created equal? J Nucl Cardiol 2007;14:9-14.[CrossRef][Web of Science][Medline]
8. Hillis GS, Croal BL, Buchan KG, et al. Renal function and outcome from coronary artery bypass grafting: impact on mortality after a 2.3-year follow-up Circulation 2006;113:1056-1062.[Abstract/Free Full Text]
9. Cooper WA, O'Brien SM, Thourani VH, et al. Impact of renal dysfunction on outcomes of coronary artery bypass surgery Circulation 2006;113:1063-1070.[Abstract/Free Full Text]
10. de Waroux JB, Pouleur AC, Vancraeynest D, et al. Early hazards of mitral ring annuloplasty in patients with moderate to severe ischemic mitral regurgitation undergoing coronary revascularization: the importance of preoperative myocardial viability J Heart Valve Dis 2009;18:35-43.[Web of Science][Medline]
11. Pu M, Thomas JD, Gillinov MA, Griffin BP, Brunken RC. Importance of ischemic and viable myocardium for patients with chronic ischemic mitral regurgitation and left ventricular dysfunction Am J Cardiol 2003;92:862-864.[CrossRef][Web of Science][Medline]
12. Santana CA, Shaw LJ, Garcia EV, et al. Incremental prognostic value of left ventricular function by myocardial ECG-gated FDG PET imaging in patients with ischemic cardiomyopathy J Nucl Cardiol 2004;11:542-550.[CrossRef][Web of Science][Medline]
13. Schmidt M, Voth E, Schneider CA, et al. F-18-FDG uptake is a reliable predictory of functional recovery of akinetic but viable infarct regions as defined by magnetic resonance imaging before and after revascularization Magn Reson Imaging 2004;22:229-236.[CrossRef][Web of Science][Medline]
14. Baks T, van Geuns RJ, Biagini E, et al. Recovery of left ventricular function after primary angioplasty for acute myocardial infarction Eur Heart J 2005;26:1070-1077.[Abstract/Free Full Text]
15. Nijveldt R, Hofman MB, Hirsch A, et al. Assessment of microvascular obstruction and prediction of short-term remodeling after acute myocardial infarction: cardiac MR imaging study Radiology 2009;250:363-370.[Abstract/Free Full Text]
16. Baer FM, Theissen P, Schneider CA, et al. Dobutamine magnetic resonance imaging predicts contractile recovery of chronically dysfunctional myocardium after successful revascularization J Am Coll Cardiol 1998;31:1040-1048.[Abstract/Free Full Text]
17. Kuhl HP, Lipke CS, Krombach GA, et al. Assessment of reversible myocardial dysfunction in chronic ischaemic heart disease: comparison of contrast-enhanced cardiovascular magnetic resonance and a combined positron emission tomography-single photon emission computed tomography imaging protocol Eur Heart J 2006;27:846-853.[Abstract/Free Full Text]
18. Joyce D, Loebe M, Noon GP, et al. Revascularization and ventricular restoration in patients with ischemic heart failure: the STICH trial Curr Opin Cardiol 2003;18:454-457.[CrossRef][Web of Science][Medline]

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