 Thank you. Again, my name is Janice Guzman-Clark. I'm a nurse scientist at the VA trained as a gerontological nurse practitioner. I'll be presenting our next speaker who you're familiar with already. Santosh Dev is the cardiologist at the Southern Arizona VA health care system. He's also the director of cardiovascular disease at the Institute of Future Health and I actually met him I think a year and a half ago when we started doing a project. That's now a VA funded project using implementation science to improve treatment or optimal treatment of patients with heart failure into VA. So welcome, Santosh. Thank you, Janice. All right, so I'm tasked with getting us back on track. So I'm gonna sort of give you the high-level items from my talk. And just to remind the speakers, we have a timer here for 15 minutes so you can watch that when you see the red light you can wrap up. So I'm excited today to talk to you about epidemiology and population health. This is an area that I'm very interested in as far as implementing strategies to screen patients and really bring the research into practice. So if you have any interest in that, please let me know. And in fact, we are looking for a couple of participants for a focus group research study. If you have a background in primary care or general cardiology, talk to me at the break. So I'm gonna sort of go rapidly and skip some of my slides. So these are some of the abbreviations I'm gonna be using. It'll be on your CME quiz at the end. So I'm really gonna focus on what are the high-risk groups for this disease. And I think these are sort of the current state of where people are really looking right now. I'm also gonna talk about a screening tool to help identify high-risk patients. So really we want to move the needle from looking at patients who are already symptomatic to patients with early symptoms or even pre-symptomatic. So some of the cost data suggests that 4% of patients with heart failure and preserved ejection fraction have amyloid. And this paper I think is probably where that data came from. It was a relatively small retrospective series of autopsies at the Mayo Clinic comparing patients with heff-puff to those that were controlled without any heart failure. And overall four patients had significant or severe interstitial wild type ATTR deposition. So to my knowledge, this is probably where that data comes from. So, you know, what's the overall rate of amyloidosis in the general population? And I don't think we have a perfect answer to that, but in this series from Italy about 12,000 patients had already received bone, excuse me, scintigraphy for a non-cardiovascular indication. So oncology or rheumatology. And so they went back and looked at what was the uptake in the heart. And about 1 in 277 patients had incidental DPD positive scintigraphy. So that's less than half a percent. But you can see that there's a high association with increasing age and gender. So it was about 1.2 percent in men over 80. And then what's the, you know, current trends in cardiac amyloidosis? So this was probably the most contemporary series, and this is from Germany looking at a large health insurance population inpatient and outpatient. And they looked at any sort of code for amyloidosis accompanied by heart failure. So these are presumed cases of cardiac amyloidosis with age greater than 60. And they saw a three-fold increase in prevalence and two and a half-fold increase in incidence over a roughly 10-year period. And the greatest increases were in men 80 years of age and older. So this suggests that ATTR is increasingly being diagnosed. And also, it was very interesting, they looked at the outcomes and the median survival was only 2.5 years. Now they did not distinguish between ATTR and AL amyloid. However, the, you know, the population characteristics suggest that it was mostly ATTR patients. So this survival is lower than, you know, typical smaller studies of ATTR patients. So this is somewhat eye-opening. And the the one-year survival overall was 70 percent. And even in 2018, the most recent year of the study, one in four were dead after one year. And there's a high burden of disease. In the year after diagnosis, the median number of outpatient doctor contacts was 40. So that's almost once a week. There's also some evidence of geographic variation. So this study from 2000 to 2012 looked at cardiac amyloid heart failure hospitalization. And you can see in the panel A that there was a high hospitalization rate in red around Rochester, Minnesota, as well as in northeast from Boston to roughly Washington. And these are most likely areas that are associated with amyloid centers. But it also suggests a disparity where you have very low rates of prevalence cases, for example, southeastern Arizona and New Mexico. And if you look at the incidence panel B, there's a similar trend, although it's not quite as striking, where newer cases are still being diagnosed in those large centers. And the increase in incidence was also seen similar to Germany, where you had a multiple increase in prevalence rate and incidence rate, predominantly in men aged greater than 75 and in the black population. Again, suggesting that ATTR is what is responsible for these trends. Similar findings were associated when we looked at death rates from cardiac amyloidosis. And the panel A, the red and orange are the total percent black population. And so you would expect to see a very high rate of cardiac amyloidosis in those states. And despite that, they had the lowest death rate in panel B. So suggesting that there's a huge discrepancy and under diagnosis of cardiac amyloidosis in those states. So the question is, well, what is the population prevalence of ATTR in sort of the most common patient population, which is heart failure? And so this study looked at 1,200 consecutive heart failure patients in several counties in Minnesota, aged greater than 60 with left ventricular hypertrophy, with preserved or mildly decreased ejection fraction. And so all patients were offered systematic screening starting off with a PYP scan. And one-third of the patients agreed to screening. The median age was 78. Only a quarter had been hospitalized. So this was large in the ambulatory population. And impressively, you can see in panel A, systematic screening was associated with a five-fold increase in detection of ATTR. And when you break it down by gender, there was a 10% prevalence in men compared to a much lower prevalence of about 2% in women. But interestingly, none of the women were detected unless there was systematic screening approach. So the sort of usual care or clinical diagnosis did not lead to any cases diagnosed in women. And again, there was a striking prevalence with age. And you really start to see things take off in 70 to 79 and going up to 889. And in greater than age 90, 20% of subjects had ATTR diagnosed, which is really amazing. So overall, one in 20 patients that was screened had ATTR. And the highest yield was in men older than age 80. So patients who are undergoing evaluation for transcatheter eridic valve replacement, this is another high-risk population. In this study, looked at three different centers, approximately 400 patients who were evaluated for TAVR. And they wanted to see what was the outcome in patients with cardiac amyloidosis. And they found that, first of all, many of the patients with amyloidosis were denied surgery. There was a two-to-one higher likelihood of receiving surgery if you had lone eridic stenosis. But that being said, one out of eight patients who was referred for TAVR had a diagnosis of cardiac amyloidosis. So that's written as ASCA, so 12%. And most of those were high-grade. And if the patient had been selected for TAVR, then the outcomes were technically not different between the lone AS versus the ASCA patients. So if they were healthy enough to undergo surgery, they had a reasonable survival, suggesting that these patients should not be denied surgery. And the authors developed a risk score. And if you had a score of two points, there was a very high sensitivity of 94% with a specificity of 52%. So you can detect most cases of cardiac amyloidosis in using the score. And I think this is a great model for centers and clinicians who are evaluating these patients. So a couple other populations are carpal tunnel and spinal stenosis. And there's a really intriguing article showing that 10% of patients undergoing carpal tunnel release surgery had amyloid deposits. But interestingly, not that many of them actually had active cardiac amyloidosis at the time. And so the Cleveland Clinic is using this protocol. So if a patient is a male greater than age 50 or a female greater than age 60 and they have bilateral carpal tunnel, they are getting a biopsy at the time of carpal tunnel release. And if they have just one of those Tier 1 factors or if any of the Tier 2 factors, that combination also leads to a tissue biopsy. And if the patient is congo red positive, then they undergo further screening for cardiac amyloidosis. And this was a nice case example in which they showed that a patient that had congo red positive at the time of carpal tunnel release had normal scintigraphy and was essentially asymptomatic. However, four years later, they had a positive PYP scan, although they didn't have any evidence of LVH. Suggesting that these patients, you know, may be pre, you know, have a early detection of future cardiac amyloidosis. And this was a nice study that retrospectively looked at patients that had already undergone bilateral carpal tunnel surgery, looking back five to 15 years. And 5% of the entire sample had evidence of cardiomyopathy. This was nearly 10% of men. And if you're a man greater than age 70 with a normal BMI, it was a 21% rate of amyloidosis. So that was really a good example of how to find these patients. And Dr. Maurer is probably going to speak on this, but as far as spinal stenosis, similar findings where there's a fairly high uptake of congo red at the time of spinal stenosis surgery. However, a very few of the patients in this series, for example, actually were PYP positive and received treatment. So black patients because of the high rate of the V142I mutation are at roughly twice the risk of heart failure. And so this is another high risk population. So I'll leave you with this risk score. The Mayo Clinic looked at population of patients had been referred for cardiac amyloidosis referral into cardiology clinic. And they developed this risk score using available variables. So they excluded some variables that were not available, such as biomarkers, ECG, or there was some missing data. So they settled on this score, which combines age, gender, presence of hypertension, ejection fraction, posterior wall thickness, and relative wall thickness, which is the sum of septum posterior wall divided by the dimension, LV dimensions. And if you have a score of six or greater, there's a 93% sensitivity and a specificity of 62%. And interestingly, biomarker, addition of biomarkers did not help the model. So one of the nice things about this is that it has a good performance at different prevalence of the disease. So even in low prevalence states, it has a good performance. It is specific for ATTR. And it uses widely available data that is available to any clinician doing an HMP and an echocardiogram. So I hope you can see that there's some really, I'd say, primetime populations that are ready for screening. And I think the question is, you know, are we doing enough with what we already know?