Within the clinical spectrum of chronic coronary syndrome (CCS), the presence of coronary artery disease (CAD) alongside ventricular dysfunction has long been a focal point due to the lower survival rates seen in this population. Improving survival in CCS patients, whether through medications or interventions, has been a key concern for clinical cardiologists for over 40 years. The concept of stunned and hibernating myocardium, which refers to dysfunctional myocardium capable of recovering contractile function following myocardial revascularization, has long driven efforts to improve prognosis in affected patients. The search for imaging modalities that could identify dysfunctional yet recoverable myocardium, guiding decisions on revascularization, defined a generation of cardiologists. Initially, observational studies suggested that the presence or absence of myocardial viability (MV), as determined by imaging, could significantly impact the success of revascularization surgery.
However, recent randomized studies have challenged this notion, pointing to a reduction in mortality with coronary artery bypass graft surgery (CABG) in long-term follow-up, irrespective of documented viability and even in cases where there was no immediate recovery of left ventricular ejection fraction (LVEF).
Part of the controversy regarding the assessment of viability for decision-making in patients with CCS and ventricular dysfunction is due to its complex definition. What is viability, after all?
From a pathophysiological standpoint, viable myocytes are those that have not undergone irreversible damage, retaining their mitochondrial function and membrane integrity. In clinical terms, on the other hand, viability refers to a myocardium with systolic dysfunction at rest that can potentially recover contractile function following revascularization. These definitions are distinct, with the latter being rooted in the concepts of stunned and hibernating myocardium.
In 1912, Herrick conducted physiological research on myocardial ischemia, demonstrating that permanent coronary occlusion leads to acute myocardial infarction (AMI).
Viability research can be simplified into a dichotomous scenario: either we look for evidence of cell death, translated as fibrosis; or signs of life, such as membrane integrity, glycolytic metabolism, and contractile reserve.
At the beginning of the investigation, we usually have a Transthoracic Doppler Echocardiogram (TTECO) of the patient at rest, an examination that demonstrates akinetic segments and motivates the viability research. Two-dimensional assessment, based on hyperechogenic myocardium and thinning of the ventricular wall (end-diastolic thickness < 6 mm), indicates significant fibrosis and lack of viability. However, this method has low specificity, as demonstrated in a study comparing it with the current gold standard, cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE).
Using these same two methods, TTECO and CMR, contractile reserve can be assessed. In low doses (2.5 – 10 mcg/kg/min), dobutamine has an inotropic effect on dysfunctional cells. At higher doses, its chronotropic effect becomes more prominent, increasing myocardial oxygen consumption. This can lead to ischemia if there is a significant lesion in the coronary artery supplying this territory. Enhanced contractile function when using low dobutamine doses, followed by declined function at higher doses, known as a biphasic response, presents the greatest specificity for recovery of contractile function.
Nuclear medicine techniques combine myocardial perfusion and cellular metabolism to assess MV. In myocardial scintigraphy, the uptake and retention of radiotracers such as Thallium-201 (201Tl) and technetium (99mTc)-sestamibi depend on the integrity of the cell or mitochondrial membrane, respectively. The first, a potassium analogue, has Na+/K+/ATPase channel-dependent transport. The uptake of 99mTc-sestamibi, a lipophilic compound that enters the cell passively, depends on mitochondrial transmembrane potentials. Hibernation initially compromises the uptake of radiotracers. This image is then compared with the acquisition after late redistribution (in the case of 201Tl, which has a long half-life) or after the use of nitrate, in which uptake is expected to define the territory as viable.
In addition to evaluating perfusion at rest, proton emission tomography (PET-CT) is based on the use of glucose by the cell. In states of ischemia, myocardial metabolism transitions from the preferential oxidation of fatty acids to glucose, given their greater energy production.
Thus, we can appreciate that various imaging modalities possess differing sensitivities and specificities in detecting MV, partly due to their assessment of MV from distinct perspectives, as illustrated in
| Method | Principle used | Sensitivity |
Specificity |
Relevant points |
|---|---|---|---|---|
| LGE | Fibrosis quantification | 84% | 63% | The combination of LGE with dobutamine in low doses increases the specificity of the method. |
| TTECO under pharmacological stress | Contractile reserve | 80% | 78% | Widely available method, but dependent on the examiner and the patient's acoustic window. |
| Scintigraphy with 201Tl | Cell membrane integrity | 87% | 54% | Higher radiation rate, prolonged examination time. |
| Scintigraphy with 99mTc-sestamibi | Mitochondrial membrane integrity | 83% | 65% | Required use of nitrate or pharmacological stress. |
| PET with 18F-FDG | Glycolytic metabolism | 92% | 63% | Less available, high cost. |
LGE: late gadolinium enhancement; TTECO: Transthoracic Doppler Echocardiogram; PET: proton emission tomography; 18F-FDG: fluorodeoxyglucose.
As previously mentioned, the use of MV in patient selection for myocardial revascularization was initially justified by a well-established pathophysiological rationale, with observational studies indicating that only patients with a substantial amount of viable myocardium benefited from myocardial revascularization.