ESC 2026 | Common pitfalls in the diagnosis and management of ATTR-CM and how to overcome them

The biggest pitfalls are in the diagnosis. So the biggest pitfall is not thinking about the diagnosis at all. And unfortunately, that’s the most common. And this is the sort of thing that once a cardiologist or internist diagnoses one patient, they start diagnosing a lot more because they know what to look for. The truth is this is not that rare a disease if you look in the right demographics. And so this is a disease predominantly of older individuals. And there is a male predominance for reasons we don’t know, but that is clearly true. So if you look at older men, an older man with a thick heart should be screened for this disease. Once you get just that, you’re going to have a high enough prevalence that it makes sense to look for the disease. Certainly, when you start adding things on top of that, like overt heart failure signs, elevated cardiac biomarkers, or extracardiac manifestations, of which the most common are the orthopedic manifestations, things like carpal tunnel syndrome, biceps tendon rupture, lumbar spinal stenosis, trigger finger, all of which are from ligament and tendon involvement. You start seeing those, and it should even set off more alarms and bells and whistles. But the point is you don’t even need that. Older patient, particularly older man, thick heart, you should think about it. Now, the good news is it’s actually very easy to do the diagnostic screening. There’s really just two steps. The first, and this is the next big pitfall, is doing monoclonal protein screening. And unfortunately, monoclonal protein screening is not something that cardiologists are that used to doing. Hematologists, oncologists are, cardiologists are not. And so trying to educate them that you really need to look for a monoclonal protein on a serum and urine protein electrophoresis with immunofixation, and then do a serum-free light chain assay, and then trying to educate how to interpret a serum-free light chain assay, and that it’s okay to have a mild kappa predominance with worsening kidney function, but it’s not okay to have a mild lambda predominance. So all of these subtleties are where some of these pitfalls happen, but the biggest one is people just not doing the monoclonal protein testing. The second step is to do imaging, assuming there’s no monoclonal protein, and that is imaging with what we call bone scintigraphy, which in the United States is mainly with PYP scans, technetium-99m magnesium pyrophosphate. In some other parts of the world, including Europe, there’s a tracer called DPD that’s very similar. This takes advantage of the surprising but true fact that hearts with amyloid deposits, and particularly ATTR amyloid deposits, take up bone tracers. And so if you give a bone tracer to somebody with ATTR amyloid, you will see at least as much uptake of that tracer in the heart as in the bones, and we usually compare it to the ribs, and often more uptake. And so if you see that and there’s no monoclonal protein, you’re done, you’ve made the diagnosis. The challenge is in AL amyloidosis, you can have a positive bone scan and you can have a negative bone scan. So what it means is that if there’s a monoclonal protein, that test is worthless. And all of us who care for these patients have seen tragic cases where AL patients were missed and either told they didn’t have amyloid at all because their bone scintigraphy was negative, or were told they did because their bone scintigraphy was positive, but it was actually AL all along and they were treated for the wrong disease. So those are the big pitfalls. I would say therapy pitfalls. Again, disease-modifying therapy, it’s not that hard. We have three good options. I think there’s almost never a reason not to offer a patient one of those three options. I think sometimes the therapy pitfalls come from the other managements of the patients. So it’s pretty clear that SGLT2 inhibitors make a big difference for patients. They should probably just about all be on one. Mineralocorticoid antagonists almost certainly help as well. And then an evolving space has been the management of atrial fibrillation, which is so common in this disease. And as ablation techniques have gotten better, I would say from my experience, I now send many more patients for ablation, and I think it clearly makes a positive difference for them. So I think there’s some gaps that can improve the overall care around some of those areas. The disease-modifying therapy, it’s crucial, but I think it’s pretty straightforward once a diagnosis is made. The last point I will make for diagnosis is that all patients should be offered genetic testing because there is an inherited form of the disease. And of course, if it’s a 90-year-old, it’s pretty unlikely they have it, but you never know, and we still recommend the testing. But in a younger patient, it’s really critical, among other reasons, because it has implications for family members.

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