Number 20, 2003
Hibernation preconditioning

Cardiovascular magnetic resonance imaging of dysfunctional myocardial tissue in ischemic heart disease

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Anna S. John, Dudley J. Pennell
CMR Unit, Royal Brompton Hospital and National Heart and Lung Institute, London, UK
Correspondence: Dr Anna John, CMR Unit, Royal Brompton Hospital and
National Heart and Lung Institute, London, UK.
Tel: +44 7351 8800, fax: +44 7351 8816, e-mail: a.john@rbh.nthames.nhs.uk

Introduction
Dysfunctional myocardial tissue is characterized by wall motion abnormality. If significant amounts of myocardium are dysfunctional it may result in clinical heart failure. In the context of ischemic heart disease, dysfunction can be due to acute or chronic ischemia, or infarction. To optimize treatment it is of crucial importance to differentiate between viable and nonviable myocardium.

Ischemia

Stunning
Myocardial stunning is defined as reversible contractile dysfunction that occurs after a period of myocardial ischemia. It persists for a period of time after myocardial perfusion has returned to normal. Stunning has been associated with thrombolysis for acute myocardial infarction, or coronary artery bypass surgery [1, 2].

Hibernation
Hibernating myocardium is defined as persistently dysfunctional but viable resting myocardium. Rahimtoola [3] postulated that myocardial function can be partially or completely restored if the myocardial oxygen supply-demand relationship is favorably altered by improving blood flow and/or reducing demand. The mechanisms responsible for hibernation are not fully understood, but it has been shown that prolonged coronary hypoperfusion due to hemodynamically relevant coronary artery disease and repetitive stunning lead to hibernation [4, 5]. Two stages of hibernation have been postulated: functional hibernation is characterized by myocardial dysfunction without structural changes within the cardiomyocyte, while structurally hibernating cardiomyocytes show loss of contractile proteins and therefore may not respond to contractile stimuli such as dobutamine despite being viable [6].

Infarction
Myocardial infarction results in irreversible contractile dysfunction due to permanent loss of myocytes and scar formation. Acutely, there is tissue edema and cell necrosis, whilst in chronic infarction scar formation occurs with an increase in extracellular matrix. Infarct size and transmural extent are important parameters to predict outcome and functional recovery after revascularization [7].

Magnetic resonance imaging of dysfunctional myocardium

Functional assessment
The first step in imaging dysfunctional myocardium is to identify the extent of dysfunction. This can be done using short-axis cines sequences spanning the entire left ventricle as well as four-chamber and two-chamber cines. Myocardial regions can be reproducibly labeled using a 17-segment model as suggested by the Cardiac Imaging Committee of the American Heart Association [8]. This divides the left ventricle into six basal, six midventricular, and four apical segments, as well as one segment covering the apical cap, which is assessed in long-axis views such as four-chamber or two-chamber views. At the same time, the short-axis cine stack can be used to calculate left ventricular volumes and function [9]. Cine imaging of the left ventricle allows accurate assessment not only of functional parameters but also of ventricular geometry. This is of particular relevance in the presence of unusual nonellipsoid ventricular shapes, for example in left ventricular aneurysm formation. Ventricular models commonly used in echocardiography do not account for deviations from the usual ellipsoid shape of the left ventricle.
Cine imaging can also help to distinguish between viable and nonviable myocardium by estimating the end-diastolic wall thickness as shown by Baer et al [10], who demonstrated that an end-diastolic wall thickness below 5.5 mm suggests nonviable myocardium.
The use of low-dose dobutamine (up to 10 mg/kg per min) as an inotropic stimulus can be used to predict functional recovery after revascularization; however, viable myocardium which has lost contractile proteins due to longstanding ischemia, ie, structurally hibernating myocardium, will not respond to inotropic stimulation.

Tissue characterization
The use of late gadolinium enhancement has become the state-of-the-art method of differentiating viable from nonviable myocardium. As shown by Kim et al [11], nonviable myocardium shows delayed enhancement with gadolinium DTPA. Using an inversion recovery sequence with an adjustable inversion time to suppress the signal of viable myocardium, nonviable myocardium appears bright in contrast with viable myocardium, which is black. Gadolinium DTPA is an extravascular contrast agent which cannot penetrate the cell membrane of viable cardiomyocytes. Therefore, viable but dysfunctional myocardium does not show late enhancement with gadolinium DTPA.
Acute myocardial infarction is associated with tissue edema, ie, an increase in the extracellular space. Gadolinium DTPA accumulates in the extracellular space and persists after it has been washed out from the surrounding viable myocardium. In some cases, in the centre of the bright infarcted area, a dark core can be found which corresponds to an area of no-reflow. This phenomenon can be explained by microvascular obstruction which occurs in acute myocardial infarction (Figure 1) [12].

Figure 1. Late enhancement in acute myocardial infarction with dark core corresponding to microvascular obstruction.

In chronic myocardial infarction, there is scar formation with an increased extracellular matrix mainly consisting of collagenous fibers. In this case, gadolinium DTPA accumulates between the collagenous fibers in the extracellular space and takes longer to clear from scar tissue than from viable myocardium [13]. This mechanism is responsible for late enhancement in chronic myocardial infarction (Figure 2).

Figure 2. Late enhancement in chronic myocardial infarction: LAD and RCA territories.

This technique allows exact quantification of the transmural extent of nonviable as well as viable tissue on a segment by segment basis, which is an important advantage over other nuclear techniques. The transmural extent of infarction has been used as a predictor of recovery after revascularization: Kim et al [7] demonstrated a direct correlation between the amount of late gadolinium enhancement and the recovery of function after revascularization. Planimetry of the hyperenhanced areas multiplied by the slice thickness and the specific weight of myocardium allows quantification of nonviable tissue in grams. Subtracted from the entire left ventricular mass, the percentage of nonviable tissue in relation to the left ventricular mass can be calculated.

Myocardial perfusion
Perfusion imaging can be used to further characterize dysfunctional myocardium. It can determine the presence of a fixed defect as it occurs in myocardial infarction, or of ischemia characterized by a reversible perfusion defect. Resting perfusion imaging is performed during injection of a bolus of gadolinium DTPA. For stress perfusion imaging, hyperemia is generated by infusion of adenosine, dipyridamole, or other vasodilating agents. Quantitative perfusion measurement is possible by calculating signal intensity time curves and deriving myocardial perfusion indices. The difference in resting and hyperemic perfusion indices is called myocardial perfusion reserve, which can demonstrate ischemia and detect the presence of hemodynamically significant coronary artery disease (Figure 3) [14].

Summary
A combination of functional imaging using cine sequences, tissue characterization using late gadolinium enhancement and inversion recovery techniques, and perfusion imaging can adequately characterize dysfunctional tissue. It can differentiate viable from nonviable and ischemic from nonischemic myocardium. This is of paramount importance in planning treatment strategies.

Acknowledgments
Thanks to Dr James C.C. Moon and Dr Andrew G.F. Elkington for contributing microvascular obstruction and perfusion images, respectively.

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REFERENCES

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