I think that guidelines in general wait many years to include new data. No doubts and many studies are necessary to include data as guideline. This fact not invalidate the importance of LGE.

There is already very good evidence for a predictive value for combined endpoints and heart failure, and borderline values for sudden death (Bruder et al. J Am Coll Cardiol. 2010; 56:875–887.; O'Hanlon et al. J Am Coll Cardiol. 2010; 56:867–874.; Editorial: Salerno et al. J Am Coll Cardiol. 2010; 56:888–889. Green et al. JACC: Cardiovasc Img. 2012; 5:370–377.), yet for definitive answers a larger multi-center trial will have to be implemented. Such initiatives are underway.

I think that MRI adds prognostic information, however the cost of the examination is a practical issue regarding inclusion in the guidelines.

Hi Guillermo

Regarding quantification - Quantification of LGE is tricky and remains a challenge - although full width half maximum has been proposed as probably the most reproducible method (see Flett AS et al, JACC Cardiovasc Imaging. 2011 Feb;4(2):150-6), a lack of consensus on how this is best done persists and anyone that has tried quantifying LGE will tell you it is not an exact science! As an example, when assessing myocardial viability (or lack thereof), there is a reason almost everyone uses the >50% or

This is a fascinating debate and very topical.

The first problem we have with the data so far is that the studies are too small. We are good at managing these patients and so actually sudden death in centres that do alot of HCM work (ie the sort of centres that do research into it!) is rare. I must have been involved with 100's of patients with HCM in the last 3 years and am only aware of one sudden death to put it into context. So sample sizes of n=200 is just too small.

Hence, what is firstly required is large multicentre trials - I know Barry Marron's group have presented a large study (I think n=1500 sort of size) at a US conference and I hope they will be presenting at SCMR at the end of the month as I have yet to see their data. I know a couple of other large multicentee trials are being set up.

The next issue is that the presence or abcsence of LGE is not going to be any good as risk factor. In most studies around 50 - 70% of patients have LGE and most will do well. So quantification is important and an understanding of what LGE actually is...

In essence, LGE is a reflection of focal extracellular volume expansion. In general, you need to have some "normal" myocardium on view with which to see the focal ECV expansion against (this is the genreral teaching although it is not entirely true in my view - you can see cirumferential full thickness LGE for example in apical HCM in short axis - personally I think there is a cut off value of ECV in which if you are above it, you can see the LGE even without normal comparator). Hence LGE shows ECV exapnsion mostly in focal areas. This does not tell you what type of fibrosis you are studying nor that it is fibrosis at all. For example, Dr Freidrich's group above have shown increased T2 siganl in HCM thick septums, something I have seen too. This might suggest some oedema present, although I dont think we really know why we see this (Dr Friedrich will I am sure have views here). So it maybe that LGE itself is too simplistic a way of doing this.

Next issue was made by Benoy above - how do we quantify LGE? Dr Marons group last published that using a cut off of 4-6SD above normal is more predicitve of NSVT than > 6SD. As Benoy wrote, Andy Flett in our group suggested the reproducability of many methods for this is poor, with the FWHM the best. But the problem is that whatever you do is arbitrary and that can never be ideal in my view. I hope that this is where T1 mapping based assessment of ECV might be helpful to get around this arbrtary problem in HCM and many other diseases, but this is my research interest and so I am biased! I will look forward to presenting at SCMR and those who are coming can see what they think of what I have found!!

Lastly, I would argue that some "conventional" risk factors are also problematic... I spend every tuesday morning presenting CMR studies to a meeting of inherited CV disease Consultants - they want to know if the septum is > 3cm thick. But this number is based on very old echo data and we know now that even with better echo imaging this sort of measure is not very reproducable between operators. Even on CMR where you can see the anatomy beautifully, the question is what do you measure. How much septomarginal trabeculation do we include? I sometimes present a measure of 27mm but say that you can make it 30mm if you want me too (ie include more SM trabeculation). This is a ridiculous thing to sayI I believe that this and LVOT obstuction really need be revisited too for example.

Current ACCF/AHA guidelines (2011) now recommend the use of DE-CMR in selected patients with known HCM when sudden death risk stratification is inconclusive after documentation of the conventional risk factors (Class: IIb; level of Evidence: C)

Two small things: Regarding quantification, I agree that currently used methods trying to be better than eye-balling are limited, although new approaches may allow to reduce user bias (Vermes et al. J Magn Reson Imaging. 2012).

Edema in HCM: I think this may represent repeated ischemic stunning in hypertrophied myocardium with relative coronary insufficiency. This is supported by observationns from Sipola et al. showing significant regional perfusion deficits in such regions (Sipola et al. Radiology. 2003; 226:129–137).

Cheers

I'm not so sure how much T1 mapping will add to DE in HCM. T1 mapping is still an evolving technique with a lot of limitations, imho. Coronary flow reserve is likely a much better test that T1 mapping. Unfortunately, there is only 1 study out there evaluating the clinical outcome of HCM patients with different degrees of microvascular dysfunction. By the way, I don't think there is a good correlation between edema by T1 and ischemia by any modality.

Dear Dr Bravo! I have carefully read the ACC/AHA (2011) guidelines. Just for it I make this question. As you know LGE is proposed as an "other potencial SCD risk modifiers" like LVOT obstruction, LV apical aneurysm and genetic mutations. Some features currently limit the role of LGE as an independent risk marker. Obviously, when you find a HCM patient with prior cardiac arrest, Sustained VT, family history of SCD (1st degree), LV wall thickness more than 3 cm or recent unexplained syncope, ICD is recommended. Doubt appears when you have a HCM patient with NSVT or abnormal BP response in the exercise test. In this case, indication for ICD is uncertain (class IIb) and last guidelines recommend ICD if other SCD risk modifiers are present (as LGE). My practical question is, would you recommend an ICD to a HCM patient with NSVT or abnormal BP response and LGE on CMR? And the second question is, when we get a consensus on the appropiate imaging protocols or mainly a threshold for detection of LGE, do you think LGE on CMR will become an independent SCD risk factor? Thanks to everyone for your expert opinion! This discussion is becoming more and more interesting!!

I think LGE may potentially become in an independent risk factor, however, I have my reserves regarding the real utility of it. First of all, it seems that LGE is a fairly common findings in HCM. The prevalence of LGE varies from study to study, but it seems to be around 50% in most reports. Therefore, the question I have is how come such a prevalent finding can be considered a risk factor. I obviously don't know the answer, but I think that the location and extent of DE may be additional clues that haven't been eluciated very well. I certainly don't think that T1 mapping will do better than LGE for risk-stratification. In summary, in my opinion LGE is important, but it should not be considered alone yet, during the decision-making process for ICD placement for primary prevention.

Ok, here goes with my thoughts. A fascinating discussion from all. I would echo the thoughts of some of the contributors here. From my perspective- 60+ % of patients with HCM have evidence of LGE. The annual incidence of SCD (depending on whether its from a tertiary referral centre or community) is between 1-3%- hence there is a discrepancy between the two. We have shown that it is the amount of scar that is more relevent rather than the presence or absence. LGE studies in IHD reflect this also- where the more scar you have the worse the outcome, with scar volume being a stronger predictor of outcome incl approp ICD therapies than EF alone. While there may be continued debate on how best to quantify scar, I think in general any ROC cut off for scar % is likley to be inaccurate and not physiological. We know that risk increases with increasing scar volumes and while there may be a sens/spec issue with an arbitrary ROC cut off, I suspect this would not enter clinical practice. The risk based on peak wall thickness shows a cut off of 30mm but this is based on an ROC cut off-. Clearly we woudl not suggest that someone with a wall thickness of 28mm is not at risk vs he/she with a wall thickness of 31mm. The risk rises we can agree. The same should apply to LGE and quantification- perhaps we can guide risk based on visual severity but we dont as yet have that information. I believe LGE will be an independent risk factor- but I suspect its main clincial role will be the presence of at least moderate LGE plus another risk factor to guide device therapy. Furthermore, I think the risk of AF/CVA and HF is a more considerable issue in HCM management, and LGE has an important role to play here- it may be that we opt for anticoagulation before AF develops based in LAVI and LGE %, and we will also need more studies on the role of current and novel antifibrotic agents based on T1 mapping, and LGE- perhaps altering the "natural hx" of fibrosis may reduce SCD risk, reduce HF, and AF. James Moon's group have also published recently on serial changes in LGE over time in HCM and this is of major importance- this is why I serially scan my HCM patients, perhaps not every year, to see if they are a subset of individuals at greater risk of HF development, especially if LGE is progressive. Hope that helps.

A very interesting discussion, just to echo a few points.

LGE is nearly ubiquitous in patients with HCM, the amount of LGE can vary and can increase over time. Increasing LGE is associated with worse cardiovascular outcomes.

However the amount of LGE varies with the quantification technique used. Also, in HCM, the boundary between normal and abnormal tissue is more difficult to quantify than in the case of myocardial infarction, as would be expected for a more diffuse disease.

This is where T1 mapping/ECV should be able to play a role; a quantitative technique would be able to give a global burden of fibrosis, and I feel would complement LGE. Changes in T1/ECV could be tracked over time per patient. Finally, it presents a treatment target.

Finally, T1 quantification has much potential for the quantification of oedema, for example, Ugander and colleagues found that myocardial oedema as detected by T1 (or T2) mapping correlated nearly perfectly with the ischemic area as measured by microspheres (JACC. Cardiovascular imaging. 2012;5:596-603)

I agree wit Rory that the large gap between the incidence of LGE vs events requires us to think about combined criteria.

T1 mapping sure will have its role or even replace LGE. that will also allow for assessing the myocardium for diffuse fibrosis. Especially for sudden death (where the LGE data are not very convincing) this may be relevant, since the grey zone data in MI indicate that the inhomogeneity of tissue with speckled fibrosis may actually be more relevant than the absolute mass of scarring.

Good discussion.

Well, already it is.

DOI: 10.1093/ehjci/jeaa423