The utility of myocardial viability imaging hinges on the premise that recovery of left ventricular (LV) function in ischemic heart disease can be achieved through coronary revascularization and results in improved outcomes and quality of life. Rahimtoola first characterized that chronic impaired coronary perfusion resulted in impaired contractility, which he termed hibernation.¹ He suggested that a heart with reduced LVEF from hibernation could be improved by revascularization. The challenge since that time has been for viability imaging to identify those patients whose hearts will recover function and who will subsequently experience improvement in quality of life. It is a challenge that remains valid and alive 30 years after those early descriptions.

Emerging data from ischemic heart failure statistics have highlighted the plight of these patients. Mortality rates remain disconcerting high; all-cause mortality at 10 years is approximately 70% of medically managed and 60% of surgically treated individuals in the younger population and even higher in older patients.² Mortality can also be high early in the course of the condition, depending on the treatment chosen. Mortality at surgical revascularization can be as high as 8% within 30 days even with modern operative techniques.² The need, therefore, remains to accurately, thoroughly, and thoughtfully evaluate patients with ischemic heart failure to optimize management decisions.

In this chapter, cardiac PET viability assessment is described and five areas of emerging data are covered:

1. 
   

   The STICH trial and STICH viability substudy

   
   
2. 
   

   PARR-2 and Ottawa Five: has time altered the figures?

   
   
3. 
   

   Quality of life outcomes: cardiac PET viability assessment can help

   
   
4. 
   

   Combination of PET and MRI to refine and redefine viability definition

Two types of dysfunctional but viable myocardial segments are described: stunned and hibernating. Stunned myocardium is the result of short episodes of ischemic insults that cause a temporarily depressed contractility in the corresponding area with no infarction. This phenomenon is generally associated with normal resting coronary blood flow. In contrast, hibernating myocardium reflects reduced resting perfusion and down regulation of coronary blood flow that is thought to be the result of repetitive ischemia with retained glucose metabolic activity.³ The net result in terms of a reduction in LV contractility is observed with both stunning and hibernation. Stunning may recover spontaneously, while the persistent dysfunction of hibernating myocardium has the potential for LV functional recovery following adequate revascularization. These pathways are described in Figure 9-1.

Scarred myocardium from previous myocardial infarction or chronic ischemia is to be distinguished from viable (stunned or hibernating) areas. Some myocardial segments may contain both scar and viable proportions, typically referred to as nontransmural scar. At a segmental level, the ratio of scar to viable myocardium will determine whether revascularization of that area may restore normal contractile function. The net balance of scarred versus viable myocardium from each LV segment determines whether global improvement in LV ejection fraction is likely to be observed following revascularization.

Generally the assessment of viability is reserved for patients with low-ejection fraction, often considered as 35% LVEF or less. The evaluation of myocardial viability can begin by an assessment of perfusion, either with SPECT or PET. Ischemia detected on stress/rest imaging in an area of hypokinesis indicates viable myocardium. Impaired resting perfusion may also be detected on perfusion imaging. Characteristically this is described as reduced tracer uptake on resting perfusion imaging, which does not deteriorate on stress imaging. Such abnormalities may represent transmural scar, nontransmural scar, or viable myocardium.

In order to differentiate between scar (nonviable) or viable myocardium, cardiac PET utilizes the metabolic adaptation of cardiomyocytes that have been exposed to chronic poor perfusion. Chronically ischemic cardiomyocytes shift from using free fatty acids (FFA) to glucose as their primary energy substrate.⁴ The change in energy substrate can be detected by an F-18 tracer labeled with glucose, F-18 fluorodeoxyglucose PET imaging (¹⁸FDG). Myocardial segments with preserved FDG uptake and markedly reduced perfusion is considered hibernating and viable while those with absent FDG uptake and reduced perfusion tracer uptake are considered nonviable scar.

Figure 9-2 demonstrates a cardiac PET viability study of a 66-year-old female patient with progressive dyspnea and a severely reduced LV systolic function with an LVEF of 25%. In this figure the N-13 ammonia (¹³NH₃) perfusion and the corresponding ¹⁸FDG uptake images are in Panel A. On the perfusion images there is a moderate reduction in tracer uptake in the entire lateral inferior-lateral, anterior-lateral segments, and apex. In contrast there is >50% uptake of ¹⁸FDG in these areas.

These regions of mismatch between resting ¹³NH₃ uptake and ¹⁸FDG uptake are considered to represent areas of viable myocardium. In contrast matched defects with reduced ¹³NH₃ and ¹⁸FDG uptake would be representative of scar. In a case such as Figure 9-2, with a relatively large amount of viable myocardium and minimal scar volume the patient may well benefit from revascularization, and a recommendation was made for further evaluation of the coronary anatomy. Coronary angiography in this patient demonstrated 2-vessel coronary disease with a mid-LAD 90% stenosis and an occluded RCA with left-sided collaterals to the distal branches. Two 2-vessel CABG was performed to the distal RCA and LAD and postsurgical revascularization the LVEF improved to 55%.

The utility of identifying viable myocardium in an era of contemporary surgical and medical practice was recently considered in the STICH and PARR 2 studies.^5,6 In 2011, the STICH trial (surgical treatment for ischemic heart failure) was published.⁵ The trial determined to identify the role of surgical revascularization versus medical management in patients with ischemic heart disease, impaired LV ejection fraction (/=35%), and suitable coronary artery surgical targets. The trial recruited 1212 patients and randomized them to optimal medical care versus optimal medical care plus coronary artery bypass surgery (CABG). A trend was seen at 12 months for an improvement in cardiovascular mortality with CABG versus medical therapy (P = 0.05).

An investigator-selected nonrandomized subpopulation (601 patients) of the trial underwent viability imaging.⁷ Viability in these individuals was defined as 5 or more segments of abnormal resting segments but manifesting contractile reserve during dobutamine stress echo or having 11 or more viable segments on the basis of relative tracer uptake at SPECT imaging. In this nonrandomized population of patients the substudy determined that preoperative viability assessment did not predict cardiovascular or total mortality.

Unfortunately, this substudy inadvertently gave rise to the controversial notion that viability assessment was not useful in the evaluation of patients with ischemic heart failure. This conclusion, however, does not reflect the many limitations and details of the STICH substudy.

Of considerable importance, viability assessment in the STICH trial was not randomly allocated. While randomization may have afforded some balance this would have been complicated and impractical. Nevertheless, without randomization it is possible that selection bias may have impacted the use of viability imaging. An additional important limitation to the substudy was that only a small percentage of patients that underwent CABG (19%) were deemed negative for myocardial viability. This limited the power of the analysis, and rendered a nonsignificant difference likely. Other limitations of the study included the fact that sensitive standard viability assessment with ¹⁸FDG PET was not performed nor were there any management recommendations made following viability assessment that might have optimized outcomes in the study.

The STICH viability paper should be acknowledged as an observational study imbedded in a randomized trial. It observed that nonrandomized stress/rest SPECT imaging or stress echocardiography assessment was not useful in determining cardiovascular outcomes in a population of patients with ischemic heart failure. It helped to generate a hypothesis that stress/echo or SPECT imaging may not be superior to physician gestalt, but in the setting of extreme study-design limitations. In future studies it is hoped that, if possible and practical, the limitations of STICH viability paper can be avoided.

The 10-year follow-up data from STICH were published in 2016.² An absolute 10% improvement in total mortality with surgical revascularization in comparison to medical management was seen (79% versus 68% for patients >67 years of age and 60% versus 48% for those <54 years of age for medical versus surgical management respectively P < 0.005) (Figure 9-3). The long-term data also established the high incidence of postoperative mortality in patients with ischemic heart failure (2%-8% at 30 days, depending on the patient’s age). The STICH study has, therefore, taught much in terms of outcomes in ischemic heart failure. It has highlighted the difficulties clinicians and their patients face in weighing up whether the risks of adverse perioperative events can be mitigated by potential long-term survival benefits. Whether the STICH viability paper helped clinicians formulate decisions in ischemic heart failure patients is worth considering. Firm conclusions as to the utility of stress echo or SPECT imaging to guide management strategy cannot be gleaned from these data and it remains to be determined whether evaluation with other imaging modalities might have been more useful. In leaving these questions unanswered, the STICH viability paper has perhaps highlighted, paradoxically, the critical importance of a thorough and systematic evaluation of these complex cases by accurate imaging methods. At the outset, the primary objective of STICH was to investigate the benefit of CABG versus medical therapy and the results of STICH point out that this assessment remains important for decision making.