Myocardial Viability Studies

ByM.Jawad,MD

Lecturer of Cardiothoracic SurgeryFaculty of medicine

Ain Shams University

Important Definitions and concepts

• There are two types of myocardial damage:1. Irreversible (Begins in the subendocardial tissue and

progresses towards the subepicardium.)2. Reversible• Reversible Damage is subsequently divided into :1. Stunning2. Hibernation

Stunning

• the phenomenon of delayed recovery of regional myocardial contractile function after reperfusion despite the absence of irreversible damage and despite restoration of normal flow.

Pathogenesis of stunning

Presently

There are 2 major hypotheses for myocardial stunning: (1)a oxygen-free radical hypothesis and (2)a calcium overload hypothesis

dysfunction may persist for hours or for as long as 6 weeks post-insult

time-course of myocardial stunning

both the duration and severity of ischemia determine the durationof post-ischemia/reperfusion dysfunction

Hibernation

• Hibernating myocardium is a state of persistently impaired myocardial and left ventricular function at rest due to reduced coronary blood flows.

• It can be defined as an exquisitely regulated tissue successfully adapting its activity to prevailing circumstances. (Smart Heart Theory)

• not adaptation !!! (Forced Degeneration Theory)

Smart heart theory: The process of adaptation is linked with a down-regulation in energy utilization, evidenced by a decrease in the expression of mitochondrial oxidative enzymes, and an upregulation of stress proteins . This counterbalances the effects of ischemia but at the cost of an attenuated level of contractile function.

forced degeneration theory : not adaptation, Supporting this is the finding that hibernating myocardium also contains apoptotic cells and cells with autophagosomes, lysosomes, and vacuoles.

Whatever the cause, structural remodeling would be essential to restore contractility, thus chronically impaired but viable myocardium may take weeks or months to recover once flow is restored . Interventions that bring back blood flow to the hibernating myocardium may return the myocytes to their physiologic function and reprogram the cells to normal expression of key proteins.

Stunning vs. Hibernating

• Main difference :resting myocardial perfusion is normal/near normal in stunning, but is reduced in hibernation

• Classically, hibernation was thought to occur with sustained hypoperfusion, especially during tachycardia but with adequate residual flow to allow survival of the tissue in the lack of contractile activity.

• In contrast to the extremely low flow states required to induce hibernation in animal studies, human studies suggest that hibernating tissue may have 70 to 80% of normal coronary flow. However, the normal or near-normal blood flow at rest in hibernating segments is associated with impaired coronary flow reserves.

• As a result, these segments may be subject to recurrent episodes of ischemia (caused by increased demand when the tissue has a loss of coronary flow reserve), which eventually lead to a state of persistent postischemic dysfunction

In other words, hibernation is the summation of repetitive and cumulative stunning, resulting in an apparent chronic reduction in left ventricular (LV) function

Important Definitions

• Reserve coronary flow: difference of coronary flow in rest and exercise.

• Reserve contractility: improvement of contractility after revascularization and can be simulated as much by inotropes.

Evaluation of Viable Myocardium

• The differentiation of viable from nonviable myocardium is highly relevant in patients who are being considered for revascularization.

• Many patients who demonstrate viability associated with severe LV dysfunction may still be candidates for revascularization rather than for cardiac transplantation

IDENTIFYING VIABLE MYOCARDIUM

The gold standard for the assessment of viability, in the clinical setting is limited…….Noninvasive techniques can only identify tissue that might benefit from revascularization.

Further we should know that the determination of viability is indirect and depends on a given region’s functional response to revascularization.

Key non invasive methods to identify viability

1.Echocardiography2.Single Photon Emission

Computed Tomography3.Positron Emission Tomography4.Magnetic Resonance

Modalities1. Electrocardiography (ECG)

2. Imaging Techniques

Electrocardiography (ECG)• Q waves on the ECG were originally thought to indicate full-thickness myocardial

infarction (MI), but in fact, there is no relationship between the presence and extent of Q waves after MI and infarct size assessed by myocardial perfusion imaging, and up to 60% of regions with Q waves have viable myocardium detected by imaging techniques

• Fragmented QRS complex has been suggested as a marker of scar but was not validated in other studies

• ST-segment elevation at rest in leads with Q waves is associated with more severe wall-motion abnormalities, less contractile reserve and greater end-systolic volume.

• ST elevation developing during exercise is a marker of maintained viability

Imaging Techniques

• Ventriculography is the oldest imaging technique and is rarely used clinically today

• Other techniques depend on different characteristics of dysfunctional but viable myocardium. The most established and clinically used techniques include the following

• nuclear imaging by Positron Emission Tomography (PET) (evaluating labeled FDG uptake)

• nuclear imaging by Single-photon emission-computed tomography (SPECT) (evaluating perfusion, cell membrane integrity, and intact mitochondria with thallium or technetium-labeled agents)

• echocardiography with dobutamine (to assess contractile reserve)

• echocardiography with intravenous contrast agents (to assess perfusion)

• MRI with dobutamine (to assess contractile reserve), and MRI or CT with intravenous contrast agents (to assess scar tissue)

Indications from surgical point of view:1) Poor LV functions2) Predominantly dyspnic symptoms3) Assessment of degree of MR and improvement

(not related to viability)

Cardiac Ventriculography:

• Is an imaging test used to determine a patient's cardiac function in the right, or more typically, left ventricle.

• Cardiac ventriculography involves injecting contrast media into the heart's ventricle(s) to measure the volume of blood pumped.

• Cardiac ventriculography can be performed with a radionuclide in radionuclide ventriculography or with an iodine-based contrast in cardiac chamber catheterization. 

The 3 major measurements obtained by cardiac ventriculography are: 1. Ejection Fraction2. Stroke Volume3. Cardiac Output

Conventional radionuclide (Scintigraphy)(Planar):

• A thallium stress test is a form of scintigraphy, where the amount of thallium-201 detected in cardiac tissues correlates with tissue blood supply.

• Viable cardiac cells have normal Na+/K+ ion exchange pumps. Thallium binds the K+ pumps and is transported into the cells.

• Exercise or dipyridamole induces vasodilation of normal coronary arteries. This produces coronary steal from areas of ischemia where arteries are already maximally dilated.

• Areas of infarct or ischemic tissue will remain "cold". Pre- and post-stress thallium may indicate areas that will benefit from myocardial revascularization. Redistribution indicates the existence of coronary steal and the presence of ischemic coronary artery disease.

Technetium-labelled tracers have advantages over thallium:1) shorter half-life with lower radiation exposure to the patient, 2) higher energy gamma emission that reduces soft-tissue attenuation,3) more flexibility in imaging times after stress4) the potential for ECG-gated acquisition

  However,

unlike thallium:5) technetium tracers have significant redistribution, which necessitates 2 injections

of the tracer (exercise and rest) for typical stress-rest protocols either on the same day or in two different days. This may carry disadvantages since uptake depends on both perfusion and viability, and viability may be underestimated in areas with reduced perfusion at rest. In contrast, thallium uptake is independent of perfusion once redistribution is complete.

Some studies have found the technetium agent, Tc-99 m-2-methoxyisobutylisonitrile (MIBI), to be inferior to thallium for identifying viability but others have found the two to be comparable.

Single-photon emission computed tomography (SPECT): a nuclear medicine tomographic imaging technique using gamma rays.It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information. This information is typically presented as cross-sectional slices through the patient, but can be freely reformatted or manipulated as required.Positron emission tomography (PET): is a nuclear medicine, functional imaging technique that is used to observe metabolic processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide (tracer), which is introduced into the body on a biologically active molecule. Three-dimensional images of tracer concentration within the body are then constructed by computer analysis. • If the biologically active molecule chosen for PET is fludeoxyglucose (FDG), an

analogue of glucose, the concentrations of tracer imaged will indicate tissue metabolic activity as it corresponds to the regional glucose uptake.

• Commonly used radiotracers are Rubidium-82, Nitrogen-13 ammonia and Oxygen-15 water.

• PET imaging is best performed using a dedicated PET scanner. However, it is possible to acquire PET images using a conventional dual-head gamma camera fitted with a coincidence detector. The quality of gamma-camera PET is considerably lower, and acquisition is slower.

Hybrid TechniquesEven when a PET camera is available, imaging may be restricted to FDG because the half lives of 13N and 15O are too short to allow imaging without an on-site cyclotron. Thus, FDG imaging for myocardial viability has been combined with SPECT tracers. This hybrid approach has proved successful. It is now also possible to image FDG using a conventional gamma camera, either using high-energy SPECT protocol or gamma camera PET protocol .

Cardiac MRI ,Functional MRI

Can Assess:1. myocardial viability (through measurement of end-diastolic wall thickness)2. contractile reserve (dobutamine stress)3. scar tissue(through contrast enhancement)4. accurate measurements of LV and RV volumes and ejection fraction

AKINETIC SEGMENTNO SCAR ON MRI

VIABLE

SEGMENT BECAME FUNCTIONAL POST REVASCULARISATIONREVERSIBLE DYSFUNCTIO

N

AKINETIC SEGMENT

SCAR ON MRI

NON VIABLE

SCAR AND AKINESIS WAS PERSISTENT POST REVASCULARISATIONIRREVERSIBLE DYSFUNCTION

Combination of PET with CT or MRI PET scans are increasingly read alongside CT or magnetic resonance imaging (MRI) scans, with the combination (called "co-registration") giving both anatomic and metabolic information (i.e., what the structure is, and what it is doing biochemically). Because PET imaging is most useful in combination with anatomical imaging, such as CT, modern PET scanners are now available with integrated high-end multi-detector-row CT scanners (so-called "PET-CT"). Because the two scans can be performed in immediate sequence during the same session, with the patient not changing position between the two types of scans, the two sets of images are more precisely registered, so that areas of abnormality on the PET imaging can be more perfectly correlated with anatomy on the CT images. This is very useful in showing detailed views of moving organs or structures with higher anatomical variation

PET•CT cardiac perfusion and viability mismatch study

Technique Emission Capturing  

Conventional :1) 201 Thalium2) 99m Technetium

(sestamibi/tetrofosmin)

γ rays Gamma Camera 2D

SPECT (Thalium/Technetium)

γ rays/photon 2 Gamma Cameras or SPECT/CT

3D

PET18FDG13N15O

γ rays/ Positron PET scanner or 2Gamma Cameras or PET/CT

3D

Hybrid PET/SPECT protocols

   

CMR    MRI  

Echocardiography

-Extremely useful tool-document the early and late functional changes at rest,Stress echocardiography with dobutamine has also been used to identify viable, yet chronically dysfunctional myocardium.

Multiple, step-wise doses of dobutamine is administeredBasally the hibernating tissue may be hypokinetic , akinetic or dyskinetic.With dobutamine infusion, it may demonstrate a biphasic response-

at lower doses(5–10mg/kg/min), an improvement in contractile

performance at higher doses (>15mg/kg/min)

Contractility regresses as the metabolic demand stimulated overwhelms the tissue’s capacity to respond

Value of Dobutamine stress echoReductions in blood flow that lead to hibernation likely do so across a significant range of flows, with a corresponding spectrum of metabolic reserve. Those regions with greater metabolic reserve will likely retain the ability to respond to an inotropic stimulus while those regions with profoundly reduced flow—just on the threshold of viability—will have no ability to respond. Such regions will therefore appear to be nonviable on a dobutamine-echocardiography challenge.Hence dobutamine-echocardiography may be considered an easily accessible tool however with sub-optimal sensitivity for the detection of residual tissue viability

Myocardial contrast echocardiographyMyocardial contrast echocardiography (MCE) using intracoronary contrast administration has emerged as a modality for assessing myocardial perfusion, and it has the potential to predict myocardial viability.Basis :-

Myocardial contrast enhancement depends on an intact microcirculation. The combination of intravenous MCE and destruction and replenishment contrast intensity curves have allowed for the noninvasive quantification of myocardial blood volume and velocity and, thus, myocardial blood flow.

Left ventricular opacification (LVO) obtained with microbubbles improves the definition of the LV border. This provides better quantitation of LV volume by the Simpson method. The correlation between LV volume measured with cardiac magnetic resonance (CMR) and that measured with echocardiography is better with the use of LVO. Regional wall motion analysis can also be better with LVO.

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