[0:00]Hello, I'm Dr. Stephen Hiles and welcome to our podcast on the 2023 ESC guidelines for the management of cardiopathy. I'm delighted to be joined by Professor James Burton, who's a consultant cardiologist at St. George's Hospital in London and professor of cardiovascular medicine at St. George's University of London. James, thanks for joining me. Thanks very much, Stephen. Nice to be here. So James, this is a a very important set of guidelines. The previous ones were 2013. So it's been a decade since the last ones and I thought we could perhaps start by thinking about what's really new. What are the the headline changes in these new guidelines? Yes, it's interesting, isn't it? Because cardiopathies are a diverse group of conditions that are actually relatively rare, but really important. They're really important because they often affect young people and they're often inherited, so they affect whole families.
[1:01:00]And the impact of a diagnosis of cardiomyopathy, particularly if it's inherited, can really be life-changing for patients and families.
[1:10:00]And you know, we have made huge progress, particularly in the understanding of the genetic basis of these conditions in the last 10 years.
[1:20:00]And so these new guidelines reflect a lot of that new understanding.
[1:25:00]I think the key new things are this emphasis on an integrated approach to diagnosing and managing cardiopathies and thinking particularly about the family context.
[1:39:00]So that means, you know, when you see a patient with cardiomyopathy, you're not just thinking about that patient, but you're thinking about their first degree relatives.
[1:48:00]And so there's a huge emphasis in the guidelines on genetic testing and on family screening.
[1:56:00]And then beyond that, I think the other new thing that that is important in the guidelines is a more refined approach to assessing risk of sudden cardiac death.
[2:07:00]So in some of the cardiomyopathies, we've had calculators that we've used for a number of years, but there are new risk factors that are brought in.
[2:17:00]And then in addition to that, I think some of the new therapeutics are really emphasized for conditions such as hypertrophic cardiomyopathy and for cardiac amyloidosis.
[2:29:00]So James, one of the interesting things, I think, about the new guidelines is the change in the definition of cardiopathy.
[2:37:00]And this perhaps goes back to what you were saying about the genetics and the understanding of the genetics that has has shifted the definition a little.
[2:47:00]And I think you were telling me earlier about the the shift to a sort of more precise anatomical, morphological diagnosis plus ideology.
[2:57:00]Yes, absolutely.
[2:58:00]So I think the old definition of cardiomyopathy was that it was a disease of the myocardium in the absence of other cardiac conditions.
[3:08:00]So in the absence of coronary artery disease, valvular disease, or hypertension that was sufficient to cause the myocardial abnormality.
[3:17:00]But the new definition really is more comprehensive and more accurate because it recognizes that there are situations where you can have myocardial disease,
[3:28:00]but also have other conditions and it still represents a primary cardiomyopathy.
[3:35:00]So for example, in some patients with dilated cardiomyopathy, they may have an element of ischemic heart disease.
[3:43:00]And in the past, that would have immediately been classified as ischemic cardiomyopathy.
[3:50:00]But if there's a genetic cause to it, then we'd now recognize that actually the primary problem is a dilated cardiomyopathy with a genetic basis.
[4:00:00]So I think it's a useful shift to think of it that way.
[4:04:00]And then as you mentioned, the key thing is that the guidelines say that you should make a diagnosis based on morphology and function.
[4:13:00]So is it hypertrophic? Is it dilated? Is it restrictive? Is it arrhythmogenic?
[4:20:00]And then you should add an etiological diagnosis onto that.
[4:25:00]And that etiological diagnosis is usually genetic, but it can be other things such as inflammatory or infiltrative.
[4:35:00]And that's important because the etiology then drives a lot of the subsequent management.
[4:41:00]And you were talking about how important genetics is now for diagnosing these conditions.
[4:47:00]I mean, how much of a shift has there been in the thinking about how we diagnose cardiopathy and the role of genetics in that?
[4:56:00]Well, there's been a massive shift in the last 10 years, and that's mainly because of the availability of next generation sequencing for genetic testing.
[5:06:00]So it's much cheaper and much more available, and it's something that can now be performed routinely.
[5:12:00]And I think in the guidelines, there's a really strong emphasis on considering genetic testing in all patients with cardiomyopathy.
[5:22:00]So for example, in hypertrophic cardiomyopathy, that's a class 1 indication to offer genetic testing to patients.
[5:31:00]And then for those that have a pathogenic or likely pathogenic variant identified, then you offer family screening to their first degree relatives.
[5:42:00]For other cardiopathies, for example, dilated cardiomyopathy, it's slightly less strong an indication because there's a slightly lower yield of a genetic cause.
[5:53:00]But still, in any patient with a dilated cardiomyopathy, you would want to consider genetic testing, particularly if there's a family history.
[6:03:00]But even in the absence of a family history, because, you know, we recognize that up to 30% of cases are due to denovo mutations.
[6:12:00]And so even in the absence of a family history, you can identify a genetic cause.
[6:18:00]I think it's fair to say that that's a big change, isn't it? Previously, we'd have only considered genetic testing where there was a family history.
[6:28:00]Yes, I think that's definitely a big change and that's largely because the yield of genetic testing has got higher and the cost has got lower.
[6:38:00]And so, you know, it means that even if you don't find a genetic cause, that's useful information to know.
[6:45:00]And if you do, then that really helps with the counseling of the patient, the prognostication, and also the family screening.
[6:55:00]And what about the other sorts of causes? So non-genetic causes of cardiopathy?
[7:01:00]How do these guidelines consider those?
[7:04:00]Yes, so the guidelines are quite detailed actually in going through the different etiologies.
[7:11:00]So they classify them into genetic causes, into inflammatory causes, infiltrative causes, and other causes.
[7:21:00]And it goes through, for example, inflammatory causes quite well, considering things like myocarditis and sarcoidosis.
[7:31:00]And so it really provides guidance on how to investigate and manage patients with those conditions.
[7:39:00]For example, it talks about the role of cardiac MRI and endomyocardial biopsy for diagnosing myocarditis.
[7:48:00]And for sarcoid, it emphasizes the importance of PET scanning in making a diagnosis.
[7:56:00]So it's quite detailed actually in going through the different etiologies and the recommended investigations and therapies for those.
[8:06:00]You also mentioned the risk stratification for sudden cardiac death.
[8:11:00]What are the new insights there?
[8:14:00]Yes, this is an important area because sudden cardiac death is what we really want to prevent in patients with cardiomyopathy.
[8:24:00]And so this is where an ICD can be life-saving.
[8:28:00]And so the guidelines are quite detailed actually in going through each of the different cardiomyopathies and saying what the criteria are for implanting an ICD.
[8:39:00]And I think in some of the conditions, the risk factors are a bit more refined now.
[8:45:00]So for example, in hypertrophic cardiomyopathy, we've had a risk calculator for a number of years now.
[8:53:00]That's still the recommended approach, but there are some additional risk factors now that are included.
[9:01:00]So for example, a hypertrophic cardiomyopathy patients who have a very high left ventricular outflow tract gradient.
[9:11:00]So a dynamic gradient of more than 100 millimeters of mercury, they're considered higher risk.
[9:20:00]And there's also an emphasis now on more risk factors that are associated with fibrosis on cardiac MRI.
[9:30:00]So for example, two small myocardial scars and patients with very high T1 values, which indicate diffuse fibrosis.
[9:41:00]So those are some of the additional risk factors that are now included in the guidelines for hypertrophic cardiomyopathy.
[9:50:00]And then in addition, they emphasize the importance of genetic testing.
[9:55:00]Because if you have a patient with hypertrophic cardiomyopathy who has a pathogenic variant in certain genes, for example, myC or actin, then those patients are also considered higher risk.
[10:10:00]So it's a more nuanced approach, I think, to risk stratification for sudden cardiac death.
[10:17:00]And you also mentioned new therapeutics.
[10:20:00]Perhaps we could pick up on those.
[10:23:00]Absolutely.
[10:24:00]So I think this is a really exciting area for patients and for cardiologists because there are new therapies now becoming available for conditions that previously we just didn't have specific therapies for.
[10:37:00]So for example, in hypertrophic cardiomyopathy, there's a new class of drugs called cardiac myosin inhibitors.
[10:46:00]And there's one called Mavacamten, which is now approved in the US and the UK for hypertrophic cardiomyopathy.
[10:55:00]And this is for patients who have an obstructive form of hypertrophic cardiomyopathy, so those with a left ventricular outflow tract gradient.
[11:05:00]And this drug works by reducing the contractility of the myocardium and therefore reducing the obstruction.
[11:14:00]And so for selected patients, it can be a really helpful treatment to improve their symptoms and improve their exercise capacity.
[11:24:00]So that's a big new drug in hypertrophic cardiomyopathy.
[11:28:00]And then for cardiac amyloidosis, which previously was a condition that we just didn't really have any therapies for.
[11:38:00]And it was very rapidly progressive.
[11:41:00]But now we have therapies that are targeting the amyloid process and are really modifying the natural history of the disease.
[11:51:00]And the guidelines really emphasize the importance of early diagnosis of amyloidosis so that you can then instigate these therapies.
[12:00:00]So it's particularly important to think about amyloidosis in patients who present with heart failure with preserved ejection fraction and also patients with atrial fibrillation or carpal tunnel syndrome.
[12:14:00]And then once you've diagnosed the amyloidosis, then there are new therapies that are available.
[12:21:00]So for patients with ATTR amyloidosis, there's a drug called Tafamadis that is now available that reduces hospitalizations and improves survival.
[12:33:00]And then there are other drugs as well that are also available for ATTR amyloidosis.
[12:40:00]So there's a drug called Patisiran and Inotersen, which reduce the production of the amyloid precursor protein.
[12:49:00]And then there are also some exciting new therapies that are in clinical trials that are called amyloid removers, which actively remove the amyloid from the myocardium.
[13:01:00]So it's a really exciting time for amyloidosis, which previously was a really difficult condition to manage.
[13:09:00]And now we have effective therapies that really change the outlook for patients.
[13:15:00]And I guess you're seeing more cases, aren't you, now that you're looking for it more aggressively and there are treatments that are more effective.
[13:24:00]Yes, I think that's definitely the case.
[13:27:00]I think there's a higher index of suspicion amongst cardiologists and other doctors for these conditions.
[13:35:00]And so, you know, we are picking them up more often and earlier in the disease process, which is important for these new therapies.
[13:44:00]And then in addition, there's been a lot of progress in the non-invasive diagnosis of cardiac amyloidosis.
[13:53:00]So now using cardiac MRI and bone scintigraphy, we can really make a diagnosis without resorting to endomyocardial biopsy in many patients.
[14:05:00]So that makes it a lot easier for clinicians to make the diagnosis.
[14:11:00]And I noticed that a lot of the guidelines, not just for cardiopathy, but other conditions are emphasizing shared decision making.
[14:20:00]And there's a strong emphasis on that here as well, isn't there?
[14:24:00]Yes, absolutely.
[14:26:00]And I think that's particularly important for conditions such as cardiomyopathy because as I mentioned before,
[14:34:00]they're often inherited and they often affect young people.
[14:38:00]And so the impact of the diagnosis, the impact of interventions such as ICDs and the impact of the counseling of family members,
[14:50:00]it's really important that patients are involved in all of those discussions.
[14:57:00]And the guidelines really emphasize that you should use a heart team approach and you should discuss with patients the various options and try and take into account their preferences.
[15:09:00]And that includes genetic counseling as well, doesn't it?
[15:13:00]Absolutely.
[15:14:00]I mean, genetic counseling is really important for patients, particularly when you identify a genetic variant.
[15:23:00]You're not just telling them about a condition, you're telling them about a genetic condition that may affect their siblings, may affect their children.
[15:33:00]And so it's a huge burden on patients and on families.
[15:39:00]And so the guidelines emphasize the importance of specialist genetic counselors in that process.
[15:48:00]And the guidelines also talk about the importance of registry-based research, don't they?
[15:55:00]Yes, this is also a really important area.
[15:59:00]Because as I mentioned, these are relatively rare conditions, and so it's quite difficult to do clinical trials of them.
[16:08:00]But if we have national and international registries, then we can collate data from large numbers of patients and really understand the natural history of these conditions better.
[16:21:00]And also understand what the optimal treatments are.
[16:25:00]So that's an important recommendation that is made in the guidelines.
[16:31:00]And I guess you're doing that locally, aren't you?
[16:34:00]Yes, absolutely.
[16:36:00]We have a number of different registries, particularly for conditions such as hypertrophic cardiomyopathy and amyloidosis, where we're tracking large numbers of patients.
[16:48:00]And that information then feeds into national and international registries.
[16:54:00]Well, James, thank you very much.
[16:57:00]That's been a really helpful overview of the new ESC guidelines for the management of cardiomyopathy.
[17:05:00]Thank you, Stephen.
