Cardiovascular imaging is a rapidly growing area, where technological development combined with clinicians’ demand for optimal visualisation of the heart might lead us to a situation where costs are high and evidence is sparse. Applying the correct imaging modality is thus an important task in clinical practice. The aim of this article is to discuss the present and future potential of deformation imaging by echocardiography and scar imaging by magnetic resonance imaging (MRI) in two common clinical cases of coronary artery disease (CAD).
Case Studies Description
Case 1
A 55-year-old woman with a history of type 2 diabetes and hypertension is admitted two hours after the onset of severe chest pain with radiation to the neck, nausea and vomiting. The electrocardiogram (ECG) shows ST-elevation of 2–3 mm in the inferior leads, and the patient is taken directly to the catheterisation lab to undergo primary percutaneous coronary intervention (PCI) of a proximally occluded right coronary artery. No other significant lesions are found. After the procedure, she has significant dyspnoea, and an echocardiogram is performed. The left ventricle is not dilated, but ejection fraction (EF) is reduced to 35 %, with increased filling pressures. There is akinesia in the basal inferior and inferoseptal walls, with an average end-systolic longitudinal strain of 11 % in the left ventricle.
Case 2
A 73-year-old previously healthy man with a history of progressive dyspnoea over the last six months is admitted with moderate-intensity chest pain relieved by sublingual nitroglycerine and oxygen. The ECG shows ST-depression in the lateral pre-cordial leads, and troponin T is slightly elevated to 800 ng/l.
Coronary angiography shows three-vessel disease. Echocardiography shows a slightly dilated left ventricle with an end-diastolic diameter of 69 mm, an EF of 25–30 % and an average end-systolic longitudinal strain of 8 %. There is hypo- to akinesia in the lateral and anterior walls and akinesia in the apex.
Initial Assessment
These two cases illustrate two common presentations of CAD. In case 1, echocardiography can give a quick bedside answer to the clinical problem, excluding serious complications to the infarction or procedure, and guide further treatment. Final infarct size can be reliably estimated after one week, when most of the stunning will be gone.1 This could be done by visual evaluation. In case 2, the patient should undergo evaluation for revascularisation by coronary artery bypass grafting (CABG).2
In these two cases, what would be the benefit of additional imaging, and which modality should be chosen?
Myocardial Deformation Imaging by Echocardiography
Visual evaluation of wall motion is a robust and quick way to evaluate regional myocardial function, but it is semi-quantitative. With the introduction of tissue Doppler echocardiography in the 1990s, it became possible to quantify regional myocardial deformation as strain and strain rate, mainly along the long-axis of the left ventricle.3 Strain means relative deformation, with negative values indicating shortening, and strain rate means deformation rate – i.e., the velocity of deformation. Experimental studies have shown that end-systolic strain is highly influenced by afterload, while peak systolic strain rate, most often occurring during the early third of systole, is more closely linked to regional contractile function.4 However, the clinical usefulness of these methods has been limited due to problems with noise and artefacts.5 Speckle tracking echocardiography has gained more widespread acceptance, as it has been implemented with a more user-friendly interface.6 However, definite proof of added diagnostic value over conventional wall motion score (WMS) is still lacking. After being applied in 2D, the method has now been extended to 3D echocardiography.7
What Would Be the Benefit of the Method?
In case 1, myocardial deformation imaging by echocardiography can guide therapy. Angiotensin-converting enzyme inhibitors are indicated in ST-elevation myocardial infarction (STEMI) patients with EF <40 % or signs of heart failure.8 Deformation measurements are not incorporated in the guidelines, but measurements such as average left-ventricular (LV) longitudinal end-systolic strain by 2D echocardiography seem to yield prognostic value beyond EF and WMS Index (WMSI) score,9 and may give better guidance for therapy. This has also been shown for other echocardiographic measures of LV long-axis function, such as atrioventricular plane excursion and velocity.10 For the prediction of final infarct size, deformation measurements made in the acute phase have predictive value both in ST-elevation and non-ST-elevation infarctions.11,12 Interestingly, it seems that deformation measurements may predict recovery in myocardial infarction already during the first couple of days, when WMS is still altered.1 Deformation measurements also seem to have potential for selecting non-STEMI patients who might benefit from an early invasive strategy.13
In case 2, the main aim of a further imaging procedure, apart from looking for valve disease, would be to determine the extent of scar and viable myocardium in the left ventricle. Although data on hard endpoints from randomised trials are scarce, patients with depressed LV function and large proportions of viable but ischaemic myocardium are thought to benefit the most from revascularisation.14
Low-dose dobutamine stress echocardiography has been used for that purpose for many years, with visually assessed improvement in regional wall motion during dobutamine stress being regarded as a marker of viable tissue that will benefit from revascularisation.15 Interestingly, data from a recent study suggest that regional myocardial deformation measured at rest by speckle tracking echocardiography can also be used to predict the response to revascularisation.16
Late Enhancement Magnetic Resonance Imaging
MRI is an attractive imaging modality due to its non-radiation nature, its high image quality and the possibility to acquire images in any orientation. The method has gained popularity after the development of late enhancement (LE) imaging, offering the opportunity to characterise myocardial tissue in an entirely new way. By using the extracellular contrast agent gadolinium, LE MRI takes advantage of the delayed wash-in and wash-out of contrast in areas with increased extracellular volume – i.e., scar or fibrosis. In addition, an inversion-recovery sequence magnifies the difference between healthy and infarcted tissue. This gives a method with high accuracy and reproducibility.17,18
What Would Be the Benefit of the Method?
In case 1, LE MRI would be able to give similar information as echocardiography, but it would be less applicable in the acute setting. However, when applied slightly later in the acute phase, LE MRI can visualise microvascular obstruction, which is still an unsolved complication during primary PCI and a marker of increased risk of LV remodelling and heart failure.19 LE MRI can obviously also quantify infarct size – that size being significantly larger when measured during the acute phase compared with a few weeks later.17
In case 2, LE MRI would be able to visualise the presence and extent of scar and the thickness of viable myocardium in the left ventricle. The segmental extent of scar correlates to the likelihood of functional recovery after revascularisation.20
The method has gained wide acceptance, including in the latest European Society of Cardiology guidelines for revascularisation in CAD.2 In patients with substantial dysfunction, LE MRI can visualise ventricular thrombi that might be missed by echocardiography.
Which Method to Choose?
In a setting such as case 1, there is no doubt that the vast majority of STEMI patients will be adequately imaged by echocardiography. MRI might provide additional diagnostic information in selected cases, e.g., when clinical signs, symptoms and ECG suggest a STEMI but the coronary angiogram is normal.21
In a setting such as case 2, the recent substudy of the STICH (Surgical treatment for ischemic heart failure) trial questioned whether there is a benefit of viability imaging at all,22 the main question being whether surgery would be refused on the grounds of imaging alone. Although viability evaluation before revascularisation is an appealing concept pathophysiologically, there is a lack of prospective studies on hard endpoints, and most evidence comes from retrospective studies using a variety of different definitions and methods. Importantly, most of these studies were conducted before the decisive recent advances in medical therapy of heart failure. When choosing an imaging modality, the evidence is in favour of the assessment of myocardial function (using echocardiography or MRI) rather than the assessment of scar.16,23
Methodological Possibilities and Limitations
Myocardial Deformation Imaging by Echocardiography
Categorising wall motion visually is a robust and quick way of assessing regional myocardial function; it requires some experience but no post-processing. For most cardiologists, the step to quantitative deformation measurements is a large one. As computational power increases, the algorithms for calculation of strain and strain rate are increasingly complex, and the pitfalls and limitations are more difficult to understand for both clinicians and sonographers. In addition, inter-vendor differences are substantial and standardisation is difficult, probably due to technical and financial reasons.
Although strain and strain rate measurements by tissue Doppler are one-dimensional and angle-dependent, they can give important pathophysiological, diagnostic and prognostic information,24,25 especially about timing, as tissue Doppler has a high frame rate and timing is an angle-independent measurement. With speckle tracking, the different deformation components can be approximated, and this has led to a search for ‘the most sensitive direction’. From basic studies in ischaemia, we know that the different myocardial layers are tightly connected. This suggests that the accuracy of the measurement is more important than the direction in which we measure.26
In a recent paper, Becker et al.16 suggested that endocardial circumferential strain was more powerful than subepicardial measurements for predicting recovery of function after revascularisation. In a review of their experimental work with ultrasonic crystals and ischaemia, Hexeberg et al. explain why deformation in one myocardial layer can not be interpreted as representative of function in that layer.26
LV geometry can explain why endocardial deformation is larger than epicardial deformation, and consequently that endocardial changes will be numerically larger in states of reduced function in any wall layer. In light of this, one alternative interpretation of the results from Becker et al. is that inward endocardial motion can be evaluated precisely in short-axis recordings using a speckle-tracking algorithm.
Two-dimensional deformation measurements are sensitive to image positioning, and apical foreshortening is a major source of error. Three-dimensional recordings could eliminate this and should theoretically improve reproducibility. The development of 3D echocardiography has been followed by new methods of quantifying myocardial strain in such recordings. However, as the resolution, both spatially and temporally, is significantly lower in 3D compared with 2D, the need for mathematical models and smoothing has increased, as has the gap between the developing technologist and the applying cardiologist. Furthermore, patients in which the assessment of regional function and viability might be important tend to have large left ventricles, requiring large scanning sectors. This will further reduce spatial resolution and the likelihood of adequate deformation measurements. We can expect technological improvements, but a close collaboration between technologists and cardiologists is necessary to ensure that developments are going in the right direction.
Although deformation measurements by 3D echocardiography have clear limitations, the development of scanners and probes for 3D imaging has yielded technical advances that also benefit other applications. We have recently shown that frame rate in 2D tissue Doppler imaging can approach 1,000 images/second when applying 3D scanning technology, and this might allow us to resolve myocardial deformation patterns even better.27 Additionally, miniaturisation has resulted in new tools that are highly applicable and informative in a bedside setting.28
Late Enhancement Magnetic Resonance Imaging
Although the sensitivity and reproducibility of LE MRI seem superior to those of echocardiography, LE MRI has some important limitations. First, the cut-off value for prediction of viability, defined as functional response to revascularisation, is not defined. The initial landmark study by Kim et al. showed a gradual decreasing likelihood of response to revascularisation with increasing segmental infarct transmurality.20 In the large group of segments with 25–75 % infarction, the prediction of recovery was not very accurate. Second, although image quality is very good in general, the grading of segmental infarction can be challenging, especially in short-axis slices near the apex, due to partial volume effects.
Assessment using both short- and long-axis images is an advantage. Third, as mentioned above, the infarct size relative to LV mass decreases with time after an infarction. This suggests that cut-off values for viability might need adjustment over time. Finally, there is no consensus on pixel intensity cut-off for defining infarction relative to normal myocardium.29
In clinical practice, LE MRI should always be evaluated in combination with the MRI cine images. Wall thickness, which is also a well-known predictor of response to revascularisation, can be accurately measured, but wall thickening can be difficult to quantify due to the effects of trabeculae that are merging in end-systole. More advanced methods for quantifying deformation, such as tagging and strain encoded MRI (SENC) have been available for quite some time and seem promising, but temporal resolution is still somewhat lower than in echocardiography.30
Future Perspectives
Echocardiography, with its versatility of methods and high applicability, will continue to be the workhorse in cardiac imaging of patients with CAD. We should be aware of the additional information we could get from deformation methods, especially due to the high temporal resolution in tissue Doppler. Deformation measurements in 3D images are still limited by the lower resolution compared with 2D but will continue to improve. The standardisation of image analysis and the collaboration within the echocardiographic community to conduct larger studies will be important tasks in the attempt to establish evidence for the new methods. LE MRI is a method with unique properties and will continue to be an important alternative in selected patients and settings, as well as an invaluable research tool.