 Hi, I'm George Eunice. I do not wear stockings. I don't know if that makes me less cool than the last two people I'm in charge of the STEMI and PCI programs here And I'm going to talk a little about ACS and acute MI syndromes particularly in women and how that differs from the presentations we normally Think about in men and some statistics and data in that regard In a case presentation too, so ACS affects 390,000 women a year Worldwide outcomes in women are worse than they are in men the mechanisms behind this disparity are kind of unclear But it's been shown time and time again Women are underrepresented in clinical trials, and I'll get to that a little bit later And I want to start off with a case This is you know when I started making this presentation a couple weeks ago I was trying to think of a case that I would present and then this woman just showed up that day and She just sent me one-year-old African-American woman who I've known for many years who has who's on dialysis And she has hypertension hyperlipidemia Diabetes hypothyroidism and a recent UTI as well as a history of prior bypass and a PCI With a Stengen-Olimax LED at the anastomosis, which was done at bentob two years ago She presented to the ER with nausea and vomiting all night long abdominal pain and her adjuvant was painful and tender depalpation During dialysis the day before she had a little chest pain her blood pressure Blood pressure was up in the 210s over 90s at that time She had recently been evaluated in this hospital for atypical chest pain just in February and had a normal stress test and normal Like many of you may I get texts with consults. This is the actual consult that I received called it into your office ESRDCED chest pain and chronically elevated troponin. So I was okay. Well, I told my fellow to go check it out Let me know what's going on So here's her labs These are old from July and this is when she came in here's your chronically elevated troponin And it's a little higher But you know a dialysis patient is hard to interpret what to make of that the CK is a little higher But it's not dramatic either the MB is a little higher, but it's not dramatic And she's denying any chest pain saying she just has abdominal pain Here's her EKG from August that was in our system really not much to speak of there and Here's the EKG at 2 a.m. When she hit the ER. She started to develop T wave inversions as you can see Kind of diffusely This is a 653 in the morning. She's developing more pronounced T wave inversions as well as ST changes But she feels fine. You saw her enzymes. She just has abdominal tenderness no chest pain I mean reproducible you touch your abdomen it hurts So the broad differential diagnosis here includes ACS Mulligan hypertension elevated troponin from that or chronically elevated troponin from vomiting Abdominal pain and and the dialysis patient who knows So what we do next to calf echo just kind of watch her Psycholar enzymes Just treat the abdominal pain and see what happens I'll get back to her and tell you what happened. So different types of ACS We're going to go through an ACS. What does that exactly mean? It's any spectrum of pathological events that leads to ischemia or myocardial injury So that of course includes STEMI meaning complete thrombosis, which leads to myocardial necrosis non-STEMI where there's partial thrombosis with myocardial necrosis and unstable angina where there's a partially included vessel, but there's not Objective necrosis yet and then some overlaps and germs in between The presentation of coronary disease in women as you well know is often different than it is in men and the media is aware of this and has been trying to promote awareness of this issue and You know when you look at the medical facts women are more likely to have unstable angina than they are STEMI in Gusto to be STEMIs were shown in 37% of the men only 27% of the women and this was confirmed in the gap with the guidelines coronary registry Baseline risk factors in women women are generally older and sicker when they present with ACS Compil compared with their male counterparts Again in the same guest of TV trial they had more diabetes more hypertension more CHF and this has been confirmed in multiple studies and registries worldwide Sicker the definition of sicker here kind of varies by age Younger women are more likely to have diabetes and CHF and stroke But as women as the eight patients age women over 70 the differences are less pronounced than they are in younger women Diabetes however appears to impact women more than than in men in one study the inner heart study looking at 27,000 patients Diabetic women were 4.3 times more likely to have an LI than women who do not have diabetes Whereas the risk is 2.7 and men There is elevated risk of coronary disease and female diabetics in multiples trials and the reason for the discrepancy here is really unclear Lifestyle factors play a role for everybody But obesity seems to play a more common a more pronounced role in women under 55 who present with acute coronary syndromes, but not so much in older women Smoking as well a stronger risk factor for MI in women than in men and Particularly in younger women with a relative risk of 7.1 versus 2.3 in men Smoking is thought to be the biggest risk factor for coronary plaque erosion Which is a common mechanism of ACS that we'll get into which is different than plaque rupture, which is what we typically think of In addition, there are psychosocial factors to be aware of depression among patients with MI Depression is more common in women than in men and this is particularly more pronounced again in younger women under 55 Who are twice as likely to have depression compared with younger men Other comorbidities including chronic kidney disease are two times more frequent in women who present with STEMI And that's associated with worse outcomes Menopause is an important risk factor with menopause. You have the loss of circulating endogenous estrogen Which is thought to have a protective mechanism and the incidence of acute MI sharply rises in women after menopause However exogenous estrogen replacement therapy as we know precipitates acute events Oral contraceptives have long been associated with the risk of venous thromboembolic events Looking at whether that influences ACS there's a 15-year Danish cohort showed that the absolute risk of MI in women on OCPs was rather low But the relative risk increased with larger doses of estrogen while it was unaffected by progestin This slide sort of summarizes a lot of the things that we've talked about includes it in terms of Issues specific to women in ACS Age depression hypertension smoking diabetes obesity chronic kidney disease all these are more common in women And then there's other specific factors pregnancy which you've heard about today And I'll talk about a little bit as a risk factor for MI particularly with spontaneous coronary dissection menopause and oral contraceptive therapy So symptoms that women present with Often a little different than with men or a view of nine studies showed that the absence of any chest pain was more common with women than in men And men are sorry women are more likely to have upper back pain neck pain arm jaw dyspnea weakness and sense of dread And again, this is you know been made it into the media and particularly online Women's health.gov has a campaign to educate women on you know Don't miss your heart attack and be aware of the symptoms that that may happen And you know facts that just women often seek long you know way longer before seeking care in heart attack situations than men do This is from CMS really which is a campaign showing a lot of different ads Really or just just pictorials on what it heart attack feels like to a woman. This one is chest pain lightheadedness or sudden dizziness Swordness of breath. I like her facial expression on this one Breaking the ad into a cold sweat nausea Left upper upper body pain Discomfort in one or both arms back shoulder neck jaw and upper part of the stomach Unusual fatigue pathophysiology As I mentioned before plaque erosion is sometimes is Seeing more often in women than it is in men as opposed to plaque rupture that we normally think around think about On ibis plaque rupture may be observed and up to a third of women who have ACS and have no angiographic stenosis at heart angiography This is a result thought to be a result of endothelial dysfunction as well as leukocyte activation and inflammation But the details of why this happens particularly why more often women is not really clear And there's been some postulation of being related to coronary spasm, which we do know is more frequent in women This is a little pictorial that just shows the same sort of principles, you know plaque rupture There's a big lipid laden core which then has a lot of inflammatory cells and there's rupture in a thrombus forms that includes the whole Lumen, there is no such lipid laden core in this plaque here where plaque erosion has occurred in a thrombus has formed That's at least partially including the lumen You heard a little bit today about Prtomatinia's coronary dissection, so I won't belabor this but it Deserves a mention in this kind of a talk where the layers of the coronary or the coronary's spontaneously separate and intramural hematoma forms and compresses the true lumen and impairs intergrade flow 70% of reported cases of SCAD as they call it are in women This is what it looks like on angiography. This is what it looks like on OCT And is often associated with other diseases that affect arterial beds such as fibromuscular dysplasia lupus Connective tissue disorders, and of course is very strongly associated with pregnancy SCAD accounts for 11% of STEMIs in women and 9% of all ACS in females under age 50 So definitely to think about in young women with ACS There's no randomized data on how to best manage these patients, stents, medical therapy, bypass, everything's been done Mortality is 1 to 5% with postpartum women or sorry peripartum women having the worst prognosis These are OCT images of the pathophysiologies. I just mentioned the plaque rupture plaque erosion and SCAD over here Takasubu, I know Dr. Costello had talked about earlier today stress related cardiomyopathy are also known as apical ballooning syndrome which is often triggered by an acute emotional stress and They a pronounced LV dysfunction, which is reversible and that accounts for up to 3% of all ACS cases And it's also more common in women And up to 6% of all ACS in postmenopausal women and may take weeks to resolve or sometimes days So evaluation and management of women pretending with acute coronary syndromes If we look at the guidelines, it all it says is it's pretty much the same as for men They should be managed with the same pharmacology as men and attention to weight or renal based doses I mean, it's all the same stuff women with high risk features should have an early invasive strategy Pregnant women it's reasonable to pursue revascularization if an ischemia guided strategy is ineffective for managing life-threatening complications in a pregnant woman So no real difference in terms of the guidelines Diagnosis troponin levels ACS and women on average tend to be lower than they are in men and Probably partially from that for that reason the ACS diagnosis is missed more often in women than it is in men Women under 60 with ACS are given an admission diagnosis other than ACS more frequently than men So it's totally missed when they come in frequently There's these new higher sensitivity troponin assays that are coming out Which may allow us to detect MI much earlier than waiting four to six hours with our current troponin assays And they may have gender cut-offs, which may help improve detection of MI and women particularly in the early hours As I mentioned earlier the women have a delay to present in presentation for ACS compared with men In the Cadillac trial there was a 2.6 hour delay to presentation for men versus three hours for women since the onset of symptoms I saw one study from Hong Kong where it was pretty marked with 53 hour delay for women compared to 15 hours for men It seems like everybody was delayed in that trial This delay of course may contribute to poor outcomes that are seen in women And you know there's many factors that may play a role here including awareness misinterpretation of symptoms which may be atypical Barriers to accessing care fear of what may happen if they do go to the doctor or go seek care and embarrassment for what they may be feeling The medications in terms of treatment now and procedures that are used are similarly effective in men as there are in women There's no sex-based differences that have really been detected all in terms of effectiveness But despite this women tend to receive fewer evidence-based medications and be less likely to have invasive interventions than men are Women are less likely to have PCI and heart cath at all in STEMI patients fear women receive reperfusion with primary PCI or Litics compared with men and this persisted after adjusting for other clinical factors Adortable needle time less than 30 minutes was only achieved in 28 percent of women Whereas 35 percent of men and door to balloon less than 90 minutes and only 39 percent of women versus about 45 percent of men Women also receive less aggressive medical therapies studies have shown there's less use of aspirin 2v3a Thenopyridines heparin beta blockers and even statins the absolute differences are frequently small, but the trend is consistently seen The benefit as I mentioned for all these therapies the oral therapies is all the same as it is in men Women do have a higher bleeding risk than men with ACS and this may be from differences in body surface area and drug Metabolism form of co-kinetics, but there's no difference in efficacy What about outcomes? Women have increased bleeding and vascular access complications compared with men Particularly younger women have a much higher risk of vascular access complications compared to men as well as higher in hospital Mortality post PCI young women have twice a two-fold greater risk of early death after MI A higher risk of 30-day readmission a higher two-year mortality Women over 70 however have improved survival and lower mortality than men do Access like complications. This is a meta analysis of a lot of trials Which all show the same thing which is that women have higher access like complications and men do Where the highest risk patients are the elderly those with low BMI chronic kidney disease and congestive heart failure An analysis of some big bleeding trials replaced to acuity and horizons Nearly 14,000 women showed major bleeding at 7.6 percent of women versus 3.8 percent of men So just being a woman increased your risk of bleeding by 80 percent and women had a higher one-year mortality 3.7 versus 2.7 percent the use of bivalorudin rather than heparin Reduce bleeding as well as mortality in the in the women who were studying these trials No talk by me would be in be complete without a radial approach plug because this is something near and dear to my heart The radial approach may decrease bleeding risk in women the safe PCI trial compared access sites in women only and It was in elective patients as well as STEMI and non STEMI patients Now in the study as a whole they terminated earlier because the overall risk of bleeding was rather small in all of the patients And there was no difference in PCI access site complication rates radial versus femoral But there was a significant decrease in bleeding or vascular complications among all cats that were done in the radial or femoral approach In the rival trial women were twice as likely to cross over to femoral meaning they couldn't complete the case Radially and had to switch the growing approach. There was a higher incidence of encountering radial spasm The rate of PCI was equally successful Major vascular complications in general was higher in women, but was reduced in the radial approach Where the number needed number of radials needed to treat a complication in women was 33 versus 49 in men If you look at data from the large national database the ncdr The same trends are seen women are twice as Risk twice as much risk of having a vascular complications with a diagnostic or a PCI Vascular complications are a strong predictor of mace including a 75% higher risk of death and am I in a stroke and By the same, you know as I said before women were less likely to undergo radial procedures compared to men Smaller arteries smaller body size increased tortuosity. Those may all be factors Bleeding post PCI was higher in women than men using bleeding avoidance strategies did reduce the absolute risk of bleeding and With the highest risk being in using radial and bivalor and and that produced the greatest production and bleeding risk in women. I Worryed about women in clinical trials The FDA has Been aware that the women are underrepresented in trials and have a campaign also which you can find online Trying to recruit women to participate in clinical trials Early major trials didn't really include many women at all and they were need not even any subgroup analysis by sex So in the early 90s the NIH and FDA had a mandate to include women in more trials So if you try to look at how that works in the years before that from 1966 to 1990 Women were 20% of ACS trials whereas after that 1991 to 2000 it was 25% So I guess that's better But it's not exactly representative because over that time period women accounted for 43% of ACS patients Who presented so you know despite these efforts women are still underrepresented and it's not really clear why? In all of these mixed-sex trials particularly with ACS You know maybe there's been postulation about concerns of safety for women of child brain potential who are pregnant etc But that doesn't really explain the absence of older women in the trials People have pointed to general unwillingness of women to volunteer or higher tendency to withdraw But that hasn't been seen in hypertension trials or in single-sex trials So it's not really clear what are the barriers to enrollment of women in these situations So in summary women and men present with similar symptoms in many cases though at different rates and Women often have alternative mechanisms such as SCAD, vasospasm, plaque erosion in addition to plaque rupture that is usually seen in men Women tend to receive less aggressive invasive and pharmacologic care than men despite similar efficacy Sex-related outcomes vary by age and young women have a worse short and long-term outcomes in young men But older women have similar outcomes to older men and Representation of women in clinical trials needs the increase in order to understand these sex-related differences And so I think that the take-home is we have to have kind of a heightened suspicion for ACS when women come in with atypical chest pain Then we do in men because a lot of these patients are being missed So getting back to the initial patient that I had shown you here's her next proponent It's actually coming down from 1.66 to 1.24 her CKs are not that exciting and her MBs a little higher But again, nothing nothing that dramatic It's four o'clock now and here's her EKG at this point. Remember, you know started out looking Similar to this but but not quite as dramatically. So so again, what do we do a cart calf echo just kind of watch her what I did is I ordered an echo and you can see here that there is a I don't know if it projects well up there as it does on my screen But you know the whole answer wall on apex do not appear to be moving too well The base is kind of hyper kinetic similar to on the two-chamber view see similar findings So this is another Takasubo case which had a lot of confounders But she's a coronary patient with prior bypass and stenting and she's elderly on dialysis and wasn't a typical patient you might think of for Takasubo and Here's the UKG the next morning her EKGs are just amazing I Felt like I needed to catheter anyway, even though I was pretty certain of the diagnosis because she does have a Lima with a stent in it and you know this, you know, I thought it was probably the right thing to do You know, I thought it was probably the right thing to do So the first thing I did was an LV angiogram and this is 48 hours after presentation and she's already better So the whole apical Stunning that was present 48 hours ago has already resolved And her coronaries were fine This over here is the Lima with the stent in it the right coronary and here you can see the sirk circulation Her coronaries were fine. So just sort of highlighting some of the issues we talked about. Thank you