Historically the origin of metabolic imaging dates back to the mid-1960s when Evans et al.[1] observed that the ventricular myocardium can be visualized by scintigraphy after intravenous injection of the fatty acid oleate labeled with iodine-131. However, the breakthrough in metabolic imaging was related to the advent of positron emission tomography (PET) in the 1970s. The availability of positron-emitting radionuclides such as carbon-11 opened the possibility of labeling metabolic substrates without altering their metabolic behavior.

Visualization of metabolism allowed insight to be gained into the cellular and molecular mechanisms that establish the link between myocardial perfusion and contractile function. 

Although this exciting tool contributed significantly to the understanding of the metabolic response of the myocardium to ischemia[2] and other conditions, metabolic imaging still awaits widespread application in clinical cardiology. This is largely due to the expenses involved in the logistics of PET, which for optimal exploitation requires an in-hospital or near-hospital cyclotron. In view of the increasing costs of health care, it seems legitimate that hospital administrators and politicians continue to ask: Is PET worth the price? Are there less expensive alternate methods which provide the same information for clinical decision making?

This issue of Heart and Metabolism provides a critical analysis of the current status of metabolic imaging, with or without PET, and of alternate methods for the assessment of myocardial viability in patients with coronary artery disease, which is the most widespread clinical application of the approach. 

Assessment of myocardial viability: Is it clinically relevant?
Although most akinetic segments of ventricular myocardium correspond to infarcted regions, a variable amount of myocytes survive the acute ischemic insult and remain ‘at risk’, because critical narrowing or occlusion of the infarct vessel in most cases persists without intervention. The ultimate fate of surviving myocardium will largely depend on residual perfusion, energy demands, and the metabolic and hormonal environment, among other factors. R. Ferrari traces in his article the different possible fates of myocytes that have suffered an ischemic insult. A major point emerging from the subsequent articles, by J.J. Bax et al., and F.C. Visser and M. Marber, is that detection of criteria of viability in a chronically akinetic region by metabolic imaging represents a strong argument in favor of revascularization, for a number of reasons: First, the region may recover contractile function, at least to some extent, and thereby not only improve symptoms of heart failure, but also reduce morbidity and mortality. Second, viable myocardium in a critically perfused region may represent a substrate for life-threatening arrhythmia. Third, residual viability in akinetic regions tends to disappear gradually, even without recurrence of an acute coronary event. Because operative mortality in coronary patients with poor ventricular function is lower in the presence of viable myocardium, timely intervention may reduce the risk. Finally, preservation of even a small layer of viable myocardium in an infarcted region may prevent progressive remodeling and failure.[3] 
Taken together, available information suggests that assessment of tissue viability is of clinical relevance, allowing better stratification of coronary patients with compromised left ventricular function and optimizing selection of high-risk patients for invasive procedures. 

Metabolic approach versus “standard” diagnostic methods 
A number of properties of intact myocytes, in addition to sustained metabolic activity, are currently used to assess myocardial viability by different imaging modalities. In their articles F.C. Visser and M. Marber, and U. Schricke and M. Schwaiger, compare metabolic imaging to other approaches that have been proposed for this purpose, including nuclear echocardiographic and MRI techniques. Only a few studies have directly compared different methods. The overall picture that emerges is that metabolic imaging has a high sensitivity for the detection of viable myocytes. This is not entirely surprising because (1) small amounts of viable myocardium may be sufficient to ‘light-up’ at metabolic imaging but insufficient to detectably improve contractile function in response to b-adrenergic stimulation; and (2) myocytes in chronically hibernating regions often exhibit profound changes in the phenotype with loss of myofibrils, and consequently the ability to contract. The question whether all metabolically active myocytes in hibernating myocardium bear the potential to recover contractile function remains to be answered. 

Is metabolic imaging necessary for patient management?
I am not aware of any clinical practice guideline on the management of patients with coronary artery disease which includes metabolic imaging as an obligatory step for decision making. The ‘state of the art 2000’ of metabolic imaging published in this issue of Heart and Metabolism strongly suggests that assessment of myocardial viability may provide incremental information relevant for optimal management of selected coronary artery disease patients, in particular those with compromised ventricular function. The prevalence of heart failure, which in most cases is a late complication of coronary artery disease, will appreciably increase during the next decades.[4] Improved identification of patients in which progressive remodeling can be slowed by revascularization procedures may not only enhance the risk/benefit ratio, but also lower the cost/benefit relationship of interventional strategies. Therefore the overall benefit may well outweigh the costs associated with metabolic imaging. 

References
1. Evans JR, Gunten RW, Baker RG, Beanlands DS, Spears JC. Use of radioiodinated fatty acid for photoscans of the heart. Circ Res 1965; 16: 1–10. 
 

 
Functional recovery of subepicardial myocardial tissue in transmural myocardial infarction after successful reperfusion: an important contribution to the improvement of regional and global left ventricular function.

Bogaert J, Maes A, Van de Werf F, Bosmans H, Herregods MC, Nuyts J, Desmet W, Mortelmans L, Marchal G, Rademakers FE.

Department of Radiology, Gasthuisberg University Hospital, Leuven, Belgium.

BACKGROUND: The transmural extent of myocardial necrosis after an acute coronary artery occlusion can vary considerably. The contribution of residual subepicardial viable myocardium to global left ventricular function is largely unknown. METHODS AND RESULTS: We studied 12 patients with single-vessel disease 1 week after successful reperfusion of a first transmural anterior myocardial infarction (MI). With PET, myocardial blood flow (MBF) and glucose metabolism were measured regionally, and the viability was graded as normal, mismatch, or match with severely (<50% of normal) or intermediately (50% to 80% of normal) impaired MBF. Magnetic resonance tagging was used to regionally quantify fiber strains, wall thickening, and ejection fraction in patients 1 week and 3 months after the MI and in age-matched healthy volunteers. From 1 week to 3 months, subepicardial fiber shortening improved significantly in the match region (MBF <50%, -5.1+/-7.0% to -9.9+/-8. 7%; MBF of 50% to 80%, -7.1+/-7.6% to -14.9+/-7.9%). This was associated with an improvement in regional ejection fraction in the infarcted myocardium (29.6+/-21.8% to 43.5+/-15.5%, P<0.0001) and in normal regions (54.3+/-15.1% to 56.5+/-13.1%, P=0.013), contributing to an increase in global ejection fraction from 44.2+/-22.2% to 49. 3+/-17.9% (P<0.0001). CONCLUSIONS: Functional recovery of viable subepicardial regions is a mechanism of late improvement in regional and global ejection fraction after a so-called transmural MI.

PMID: 9884377 [PubMed - indexed for MEDLINE]

 
Paul Dudley White International Lecture. Our future society. A global challenge.

Kelly DT.

Publication Types:

• Lectures

PMID: 9184571 [PubMed - indexed for MEDLINE]