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Clinical Impact of Viability Imaging | CMR as a Prognostic Tool in Ischemic Heart Disease: Part 2
Clinical Impact of Viability Imaging | CMR as a Prognostic Tool in Ischemic Heart Disease: Part 2
2012cmrcoronarydemonstrateddiffuselydysfunctiondysfunctionalenhancementgadoliniuminfarctinfarctioninfarctionsischemicmyocardialmyocardiumocclusionpatientspercutaneousportionpreoperativeprognosticationrecoveryrevascularizationscarringsegmentsegmentalsubendocardialtransmuralUHNventricularwall
Dobutamine Stress MR  | CMR as a Prognostic Tool in Ischemic Heart Disease: Part 2
Dobutamine Stress MR | CMR as a Prognostic Tool in Ischemic Heart Disease: Part 2
2012dobutamineimprovementmodalityMRIpatientsrecoversegmentaltransmuralUHN
Hibernation Predicted by CMR and PET | CMR as a Prognostic Tool in Ischemic Heart Disease: Part 2
Hibernation Predicted by CMR and PET | CMR as a Prognostic Tool in Ischemic Heart Disease: Part 2
2012apicalappearsenhancementflowfunctionmetabolicallyMRImyocardialmyocardiumpanelperfusionpositronrecoverrestoredscarringsegmentseptalseptumstaticsystolicthickeningtomographyUHN
Patient with Impairment of Left Ventricular Function | CMR as a Prognostic Tool in Ischemic Heart Disease: Part 2
Patient with Impairment of Left Ventricular Function | CMR as a Prognostic Tool in Ischemic Heart Disease: Part 2
2012angiographicbasalbypasscontractingcoronarydemonstratesfunctionhypokineticimagesleftmyocardialmyocardiumnormalizationostialpanelpatientpreoperativeproximalseptumsurgerysystolicUHNventricleventricular
Stress Perfusion CMR | CMR as a Prognostic Tool in Ischemic Heart Disease: Part 2
Stress Perfusion CMR | CMR as a Prognostic Tool in Ischemic Heart Disease: Part 2
2012adenosineattenuationcircumflexcmrdepicteddipyridamolegadoliniuminferolateralinjectmultiplemyocardiumnuclearocclusionperfusionstresssubendocardialtechniqueUHNvasodilatorventricleventricular
Meta Analysis of Stress CMR Diagnostic Performance | CMR as a Prognostic Tool in Ischemic Heart Disease: Part 2
Meta Analysis of Stress CMR Diagnostic Performance | CMR as a Prognostic Tool in Ischemic Heart Disease: Part 2
2012angiogramangiographycenterdiagnosticlargermetasensitivitysingletrialsUHN
Paper Validation of Stress Perfusion MR Against Coronary FFR | CMR as a Prognostic Tool in Ischemic Heart Disease: Part 2
Paper Validation of Stress Perfusion MR Against Coronary FFR | CMR as a Prognostic Tool in Ischemic Heart Disease: Part 2
2012accurateassessingcoronarycutoffffrflowfractional flowinterventionalmethodperfusionreservesignificancestresstechniqueUHN
MR IMPACT Trial | CMR as a Prognostic Tool in Ischemic Heart Disease: Part 2
MR IMPACT Trial | CMR as a Prognostic Tool in Ischemic Heart Disease: Part 2
2012angiographycmrdiseasemulticenterpatientsrandomizedspectUHN
Value of Stress CMR in Ruling Out Disease | CMR as a Prognostic Tool in Ischemic Heart Disease: Part 2
Value of Stress CMR in Ruling Out Disease | CMR as a Prognostic Tool in Ischemic Heart Disease: Part 2
2012abnormaladenosineadversecardiaccmrcontractilecoronarydobutamineechoeventgadoliniumidentifyingimaginginfusedlowmibimultiplemyocardialnormalpatientsperfusionprotocolratereliablyremodelingrestingstenosisstressUHNunderwentundifferentiatedvasodilatedvasodilator
Transcript

Hello again. Welcome back to this discussion of the utility of CMR for prognostication in the ischemic disease. In the first section, we talked extensively about the use of CMR following the setting of acute myocardial infarction. But in this part of the talk, I would like to turn and talk instead about how CMR can be used to make clinically relevant decisions in patients who may have had infarctions at some point in the past, or patients who present de novo with chest pain of

uncertain etiology. Let's talk a little bit about how late gadolinium enhancement can be a useful clinical tool to identify which patients with myocardial scarring and left ventricular dysfunction are most likely to benefit in terms of recovery of function following intervention either by surgery or percutaneous coronary techniques. The classic work in this area was done over ten years ago by Ray Kimmon

and Bob Judd who performed a simple but elegant study which looked at the effect of revascularization on dysfunctional myocardium. I'd like to draw your attention to the image on the top right of this slide which is a single myocardial slice demonstrated using late enhancement techniques. You can see that most of the myocardium is diffusely black indicating that it's normal, healthy myocardium

and you can see an area in the lateral portion of the wall where there's a subendocardial scar with a superimposed portion of normal black epicardium. As part of their study, what Kim and Judd did was simply examine every portion, every segment of the myocardium prior to surgery. And then look again at function in the myocardium a number of months following surgery. In that preoperative cardiac MRI they

scored every segment according to the transmural extent of the myocardium and by that I mean some patients when they infarct have only a very small degree of infarction which is effectively confined to the the subendocardium. But many patients of the subject prolonged coronary occlusion as we discussed in part one, are likely to develop progressive and more extensive infarct within the wall. So if we go back

to the top right hand image and look at the representation here, we can see that roughly 50% of the myocardium in this segment is white and roughly 50 % is black. And so every segment in this study was coded and graded according to this segmental scheme, from 0 to 25, 25 to 50, 50 to 75% of the infarction, and 75% to transmural scar. And then in the follow up study, wall motion was assessed

for grades of improvement. And what Ray Kim demonstrated really very clearly, is that those patients who had little or no infarction in a segment that was not moving properly, had a very high chance that that segment would improve significantly in function, six months or more down the line. Conversely however, those patients

who had significant scarring, and by significant I mean 50% of the wall or more was composed of scar. Those patients actually had a very low chance of recovery of function. And so this was really the first important paper that suggested to us that we could use late gadolinium enhancement as a technique to help the surgeons decide which patients they should take forward for surgery in the setting

of LV dysfunction which is often regarded as a relatively high-risk surgery. Now of course the problem with the paper that I've demonstrated

in whom the benefit of surgery for improvement of function is uncertain. So if you have little or no scar there's a high chance of recovery on the the other hand if you have a lot of scaring there's very

little chance of recovery. But what about the patients in the middle? What about the patients with perhaps 25 to 50% transmural extent of scar? That's a very relevant clinical group that makes up a large number of patients. And late enhancement alone doesn't really seem to tell us which patients in that group are likely to recover function, if they're

revascularized. So we learned something from the stress eco-community in this regard. It's long been known lotus dobutamine is actually very sensitive and specific for predicting which segments are likely to recover and in this particular study this work was simply replicated using MRI as the imaging modality rather than Echo. And not surprisingly as is seen in the Echo literature, those patients who improved

their wall motion by at least one grade during the infusion of dobutamine were also those patients who are likely to experience a significant improvement in segmental function following coronary revascularization. So what we're really talking about in many cases,

and

we are not able to go into this in great detail today but in many cases, the clinical question that faces us as imagers, is whether myocardium is alive or dead or in some kind of intermediate down regulated state in which it does not appear to function well but perhaps if flow is improved to that portion of muscle will regain function with time. And there are a number of techniques

that can be used to predict hibernation and Positron Emission Tomography or PET is probably the best known. But I would suggest to you that MRI is also equally good in many cases, and it has the same prognostic ability. And I would like to illustrate that with two cases both taken from the literature with the references as provided. Here is a patient who appears to have a large segment of dead muscle.

If you look at panel C, bottom left , this is a standard maybe perfusion study which clearly shows an arid area where there's very little perfusion. And when you contrast that with the MR perfusion in panel A, you again see an area that clearly is darker and appears hypo-perfused compared to the lateral wall. However, when we look at panel B which is the late enhancement

image, in fact we don't see any evidence at all of myocardial scarring in this region, and furthermore, when we look at the PET image which looks at myocardial viability in terms of energetics, we can see that in panel D the area that appears to be dead in panel C in fact lights up, suggesting that this is not an area that is dead, but is an area which is chronically hypoperfused,

and has effectively metabolically down regulated, gone to sleep or hibernated. And therefore this is an area which should recover if flow is adequately restored by bypass surgery. And then if you look at panel E and F which are static CT-frames prior to surgery, you can see in F that the septum is not really thickening normally. So there is an abnormal area

of wall motion which co-relates with the area of poor perfusion. However, when coronary flow is restored and the images are reacquired six months later, after surgery, you can see in panel H, that that area of the septum is now thickening entirely normally. So this is a very good example where both PET and cardiac MRI were in brilliant complete agreement, that this was not a segment that was dead,

but was a segment that was hibernating, and was highly likely to recover following revascularization. Here's another example from the same publication. Again in A we can see there's a perfusion defect by MRI in the septum, and yet in B we can see there's no evidence of scar that may account for such a perfusion defect. Panel C show us the MIBI, where there's obviously a large

apical septal defect. Yet in the PET image in panel D, there's a lot of metabolic activity. So again, both MR and PET are suggesting that the apical septum in particular, is not dead, but is not contracting normally because myocardial flow is inadequate. And the absence of late enhancement would suggest that this is is an area of myocardium that will actually recover normal function if flow can be restored.

So again, if you look at the static CT-images in panels E and F in the top right, you can see that the apical septum fails to thicken up normally during systole. However, six months later following bypass surgery, that area has entirely recovered with normal systolic thickness. So again, not an area of the heart that was actually dead, but an area that was hibernating, and

correctly predicted by MRI. So now here is an example from my own institution where a patient was found to have significant impairment

of left ventricular function with symptoms of heart failure. And when you look at the CT image and the top left panel, you can see actually that there is very poor function in much of the heart. On this four chamber view we can see that the right

ventricle is contracting normally, but the left ventricle is really only contracting normally in the lateral basal segment. And the rest of the myocardium is either severely hypokinetic or in fact in the case of the septum itself, entirely akinetic. When we look at the late enhancement panel underneath, you can see the myocardium actually appears entirely black suggesting there is no evidence

of myocardial scar at all. And so, the question arises why is there such severe impairment of systolic function. The answer can be seen on the angiographic views on the right hand side. And it maybe more difficult for you than it is for me to see this on the screen. But in fact the top panel demonstrates a tight left main ostial stenosis, and the right coronary injection on bottom panel

shows a fairly significant, and tight proximal right coronary lesion. So in other words there are lesions which are quite likely to be causing a significant disturbance of flow and a significant reduction in flow. If we look at the same patient six months following coronary artery bypass surgery you can see in the bottom panel there has been almost entirely normalization

of function and compared to the preoperative images on the top and this is really a very striking example but not an entirely uncommon example and I think this particular case demonstrates better than anything else the prognostic power of MRI. Because when the surgeon is shown the images of the patient in the top panel, he is likely to say this is a very high risk operation and I want you to really

convince me that if I put this patient through the risk of bypass surgery that they stand to get a real benefit. And that's exactly what happened in this case. So now in the last five or ten minutes of this presentation, I would like to turn to talk to you

a little bit about stress perfusion cardiac MRI. This is a technique that's been around for at least 10 years

but has only really filtered its way into CMR consciousness over the last five or six years. It's a technique that can be considered to be analogous in many ways to that of maybe perfusion imaging. And I'd just like to talk to you through the technique which is fairly straightforward. We perform vasodilator stress on patients using either dipyridamole or adenosine just as we do in the nuclear lab.

And then we inject a bolus of gadolinium. And the difference between this technique and nuclear imaging is that we use effectively time resolved imaging, a bit like having a shutter on a camera and taking multiple shots in rapid succession. We acquire multiple pictures at every time point every heart beat in fact, after injection of gadolinium. And you see this depicted in the panel on the left,

where you can see we inject gadolinium as it appears first in the right ventricle. It then goes through the lungs and appears in the left ventricle and then subsequently causes a diffuse splash at the left ventricular myocardium or at least it should do. In this case what we see in the inferolateral wall is a subendocardial

dark region. A perfusion defect, that does not enhance at the same point in time as the normal myocardium. So this is visually what a perfusion defect looks like by stress MRI. And this was a patient who had a large occlusion of a circumflex artery. We can also look at perfusion somewhat semi quantitatively using a region of interest in both normal and abnormal areas of the myocardium, and plot

time signal attenuation curves as depicted on the right which allows us to look at various parameters such as time to peak enhancement and maximum up slope. This is more of a research tool generally. It does not tend to be used in clinical practice. So there have been a number of studies of the efficacy and diagnostic capability

of stress MR over the last 10 years and I have grouped them together

here in this image from a publication which performed a meta analysis of overall accuracy. And on the left hand side, you can see accuracy results from a number of single center trials. And I think that the message to take away here is that single center trials generally have relatively low numbers and they generally report, actually, very high diagnostic sensitivity and specificity.

And then when you move to the right hand side of this slide, and you look at some of the larger multi center trials, what you see is that a trade off between larger numbers which, presumably ought to make the data more reliable and perhaps not surprisingly a more real world diagnostic accuracy, sensitivity and specificity with overall slightly lower diagnostic capability compared to that demonstrated

in a single center studies. I'd also emphasize that many of this trials use a visual assessment and not a semi quantitative assessment. I actually think that's entirely appropriate because that's what we do in clinical routine. Perhaps more of a problem is that most if not all of the of these trials have used standard X-Ray angiography as the gold

standard, and we already know that the X-Ray angiogram in multiple studies turns out to be a poor predictor of the actual physiological significance of the coronary stenosis. Now this was an important paper that was published two or three years ago by my colleague,

Stewart Watkins, when he was working in Glasgow. And he sought to validate stress perfusion MR against not simply coronary angiography,

but a more accurate method of assessing the significance of coronary stenosis, using a technique called coronary Fractional Flow Reserve. And whilst we don't have time to go into the method in detail, it suffices to say that Fractional Flow Reserve or FFR is generally regarded by the interventional community and the imaging community as probably the most accurate assessment or the most accurate way of assessing

the significance of a coronary narrowing compared to any other technique that we have. So it's generally regarded in clinical trials, for example, as the reference standard for assessing severity of stenosis. So every patient in Dr. Watkins study underwent both stress perfusion MR, and separately, and in blinded fashion measurement of Fractional Flows Reserve. And using

Fractional Flow Reserve with a cutoff of less than 0.75, again generally accepted in the literature as being the cutoff for significance. He was able to show a very impressive sensitivity and specificity for stress MR in over 100 patients. And this I think to date is probably the best validation we have of stress MR in terms of its diagnostic potential. So then I would like to mention the most

This is the MR impact study senior authorJuerg Schwitter from Zurich who conducted a nice, multicenter and importantly multivendor trial using all three major vendors magnets. In a randomized study where patients underwent both SPECT imaging

and stress MR and coronary angiography and then they were able to look at head to head comparisons of the two techniques in several hundred patients. And actually the main message to take out from this, is that, there was a non-significant trend towards better diagnostic performance for cardiac MR on a head-to-head comparison basis and it didn't matter whether patients had single-vessel disease

or multi-vessel disease CMR was certainly not inferior to SPECT and in many cases, appeared to be superior, although with a non-significant statistical trend. Here's an example from the paper of good agreement, between CMR and SPECT, and confirmed by angiography. In the top

panels A, B, and C, you see static images from the CMR stress part of the study, you can see there's

a low intensity perfusion defect in the lateral wall. If you compare that to the appearances of the lateral wall in the SPECT on rows F and H, you can again see that it does appear to be diminished activity in the lateral wall which reverses to normal when you look at the rest images from the SPECT in rows G and J. Finally when you look at the invasive coronary angiogram,

there's evidence of a significant stenosis in the left circumflex artery in the lateral wall territory with a normal right coronary. So here an example of good agreement between CMR and SPECT in a circumflex lesion. So, finally I would like to end the presentation today,

by just discussing the value of stress CMR in not only ruling out disease, but ruling out subsequent events. So, MRI is competing for business

in the real world, with MIBI and with Stress Echo. We know both Stress Echo and Stress MIBI if normal, come with a very good warranty period. In other words, if you have a normal stress Echo, or stress MIBI, it's highly unlikely that you'll have a significant coronary event in the next three years. So a stress CMR is really to be a comparative

imaging modality, it also needs to be able to provide us with the same reassurance that a normal study means there is a very low likelihood of a cardiac event in the coming years. Now this question has fairly recently been addressed in a moderately large, single center study, where 513 patients were put into a protocol that was interesting, in imaging terms because it was a relatively

aggressive protocol, in that it used two different types of stress at one sitting, which isn't something that we commonly do. And I'd just like to go through the protocol with you in the next minute or two. First of all, patients underwent resting CT imaging. Then they were subject to four minute

adenosine infusion, to induce maximum coronary vasodilatation. And this was done in just the same way we would normally do in the nuclear laboratory. At peak vasodilatation, they were inject with gadolinium and multiple slices were required for the stress images. There was in a period of 10 to 15 minutes to allow for wash out of gadolinium. And then the patients underwent resting perfusion imaging. Following that,

patients were subjected to dobutamine stress. Now this is a different sort of stress to vasodilated stress in that works by increasing inotropy not only the rate of contaction but the force of contaction. So dobutamine was infused in stages from 10 to 40 micrograms per kilogram per minute. In just the same way as you would do if you were performing a stress Echo. And the end point here is not profusion,

but changes in inducable wall motion, or wall motion abnormalities. So every patient had both forms of stress imaging. And what was Important from this is that if you had a normal dobutamine stress, or you had a normal perfusion stress. You're adverse event rate over four to five years was actually very low. Conversely, if your dobutamine stress was abnormal, or your fusion stress was abnormal,

you had a significant increase in adverse events over a five years follow up period. Furthermore if you had both a normal dobutamine stress and a normal perfusion stress which is indicated on the third blue line here you actually had a very low event rate after three years 0.8% adverse event rate cumulative adverse rate at three years. So really a very, very low event rate comparable to

anything that has been shown by maybe perfusion or stress echo. And of course the converse was also true in that if you look at the third red line here if you have both an abnormal stress perfusion and abnormal wall motion with dobutamine you had a very high event rate at three years of almost 17%. So really although these are relatively small numbers when compared

to the very large studies that we've had over 20, 25 years from both the nuclear world and the Echo world. These are the first data that suggest reliably that whether you use dobutamine stress or vasodilator stress, if you have normal study you can save your patient with a pretty high degree of confidence the chance of you having an abnormal cardiac event in the next three years is actually

very low. So in summary in part one and part two of this talk, I hope I've been able to show you that CMR is able to reveal multiple tissue properties following acute myocardial infarction, which are actually of importance, prognostic importance in as much as they tell as something about the adverse remodeling that may occur following an infarct. I think I've been able to show you

that CMR is able to suggest which candidates are most likely to get functional contractile recovery improvement following revascularization. We've been talking in the latter half of the second talk about how stress MR is capable of reliably identifying significant that is to say flow limitings stenosis which is the stenosis of course upon which we want to intervene. And finally

I hope in the last few slides I've convinced you that stress MR whether it is dobutamine of stress perfusion stress is actually capable of identifying other low risk group of patients from among those who present with undifferentiated chest pain. I would like to thank you very much for joining me for both parts of this talk and I hope you've enjoyed it.

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