Dr. Na Mee Kim summarizes different types of cardiomyopathies and the role gender and different hormones can play while discussing gender associated triggers, co-morbidities, and mortality rates.
So DR kim is one of my colleagues and also a good friend. She's a cardiologist here with specialty training in nuclear cardiology, echocardiography, vascular medicine. She's also board certified lip pathologist and hypertension hypertension specialist. Her clinical interests include gender differences in cardiovascular disease as we're discussing today. And of course she was also critical in the development of the scripts women's heart center. As I mentioned earlier, she received her bachelor's degree from john Hopkins and her medical degree at University of michigan. And then she and I actually did our residencies together at cedar Sinai, which is where we met over a decade ago. I can't believe I'm saying that. Um and her fellowship training here in heart failure as well as general cardiology at Scripps Clinic. So I'm lucky to call her a colleague. She doesn't want me to mention this, but she did also do a certification in hormones and we call her our menopause, boarded uh colleague. But I won't throw her under the bus for that. But she may she may know more than us about the progesterone and estrogen effect. So I'm going to turn it over to Dr kim now. I'm sure you'll enjoy her talk. Thank you dr even in for that very kind and generous introduction. Um I actually want to take a moment to thank our moderator today. Doctor who wouldn't she's been so busy introducing all of us. I don't believe she's been introduced herself. Um She is one of my career mentors um and um uh doctor who didn't actually trained as we mentioned, the Cedars Sinai Medical Center in West L. A. Veterans Affairs Hospital and served as chief resident there and subsequently to her cardiovascular training and her Integrative cardiology training here at scripts where she also served as chief fellow um Doctor who specializes risk stratification and management of coronary disease, heart failure, arrhythmias, valvular disease and of course management of pacemakers. She's one of her invasive cardiologists. Um um She has strong interest in incorporating integrated alternative therapies for the management of chronic conditions with emphasis and nutrition, exercise and stress management which reflects her training an integrated medicine. And um she's um uh and I'm very happy to say that um it's really great to be part of this first conference in Woman in arrhythmia. And um and she's of course our director of the Heart um Women's Heart Center. So um thank you doctor Ruden. All right so um We hear scripts are roughly 30 cardiology strong and we have specialists in many different um um um areas of cardiovascular disease. And today I wanted to share with you a practical um clinically relevant um Talk about um sex differences and um potpourri of um different cardiomyopathy um that I thought would be good to review. Um Big topics such as heart failure with preserved ejection fraction cardio oncology. Spare part um Card in my those are very broad topics and those are often covered by our wonderful colleagues over at the advanced heart failure um team. Um one of members who is our beloved dr Heywood whose will be speaking to us after. Um this talk. So. Yeah. Oh perfect. No thank you. All right so no woman and heart disease talk is complete with some picture of red dress and women heart logo and Susan lucci. Um These are often the images that we think about um when february comes around every year and we think about heart disease and a woman. But um as cardiovascular disease is very heterogeneous group of disease um it's really important to bear in mind that there's a lot more to women and heart disease and just atherosclerosis and hypertension for example. Um This is the latest data that I pulled from C. D. C. Recently spanning 2 2017. And yes just just confirms what dr Rogers already reviewed with us. That heart disease indeed is number one cause of death for men and women. And this map is the latest map that we have from C. D. C. Um Showing heart disease death rate um in a woman over 35 in the us. And um it's very striking um um as um when you look at the legend there um and how high the rate of death is from heart disease. So just to recap one in five women died from heart disease. That's a fact in US um Heart disease kills more women than breast cancer by far. And 64 of women in some studies who die suddenly of heart disease have no previous symptoms And despite growing awareness um um very um slightly above a mature, about 50 of women actually recognize um heart disease as being important for their health. Um And of course no reasonable woman and heart disease um talk will be complete with this graph. So this graph is a graph about how we really close to um The gap um when it comes to uh death from heart disease between men and women and that vertical line, you see right around approaching um 1997 8. That's around the time when we had the first woman director of NIH dr Bernadine Healy, who in the arm who started who started a study looking into women and heart disease. So um and now we are reaping the benefits of um Um the movement back in the 90s. So basically, what do we mean when we say when we talk about sex differences really in any disease and heart disease? Well, we're talking about diseases that are specific to one sex, like para part um Karam apathy. Well, men can get it. They are never peri partum. And then again there's a broad category of other conditions um where there are sex differences when it comes to incidents, prevalence ideology, Symptomology, treatment, response, calmer um morbidity and mortality in outcomes. And these diseases are, for example, microvascular coronary disease, much more common in women. A wild type T tr Kartik amyloid, much more common in men. Um And in all of these instances the sex differences really the combined expression of genetic and the hormonal difference between men and women. And there is a lot more to be learned about sex differences in various cardiovascular conditions and it's relevant for our patients get better care. So today I want to talk about the following group of conditions and how sex differences can help um improve our patient care. I want to talk about cardio hypertrophic cardiomyopathy and um we'll also briefly talk about cardiomyopathy is that are commonly associated with systemic lupus. Erythematosus. Also just you know, usually known as lupus. Um because it is a disease that affects women proportionally will briefly talk about peri partum left ventricular non compaction and particularly fusion because they generally seem to have a more benign course. Um And that is of interest. And then we'll talk briefly at the end also about um stress, some cardiomyopathy and outcomes as well. And as I mentioned earlier, we will forgo talking about these much broader um uh conditions that are well reviewed and some of our other scripts conferences. So hypertrophic cardiomyopathy. Um Well Fiona typically it can vary. Um I think most people are very familiar with approximate septal technique, but you can have the whole of the septum that um is hypertrophy. You can we are starting to pick up many more atypical variants. Um And of course you can have a concentric hypertrophy as well with hypertrophic cardiomyopathy. It is um The most common genetic cardiomyopathy, estimated conservatively a one in five adults. But actually true prevalence may be closer to one in 200 adults. That means any given large high school. You can have many, you know students who have this genetic condition um for example, in the Mesa Cohort study where they looked at patients who didn't have any based on cardiovascular disease um on based on cardigan. Re 1.4% of the patients were uh were noted to have unexplained hypertrophy of their left ventricle. So that's really interesting. Um They're more than 1004 100 mutations that are known. Um And most of the mutations um encode components and the sarcoma, which is the structural unit of the muscle of the heart. And what's interesting about hypertrophic cardiomyopathy is that you can have the same mutation, but the way you manifest the disease can be very different even within the same family. Um The time of onset the severity of the disease and even the disease itself. Um Not everybody made half a septal hypertrophy. one may have a pickle hypertrophy and the next generation have a different myopathy manifestation. Uh for the most part um the diagnostic criteria is unexplained maximum left ventricle wall thickness of 1.5 cm. And that's generally um accepted as a diagnostic criteria. So um so looking at sex differences and hypertrophic cardiomyopathy. So um here we see that prevalence is less than women, which is very odd because this is mostly an auto is almost dominant um Disease where it should affect male and females equally. So um that is a very odd that the prevalence is much less than women. Um second women tend to be older at time of diagnosis and initial evaluation than men as um uh noted here um in the Diagram label # two. Um Number three um women tend to be much sicker and have worse um heart disease at time of diagnosis and um approach um and um subsequently um at the time of surgery to correct the hypertrophy um uh my cardi um um uh the biopsy shows that women have uh much more advanced cellular remodeling and scarring. So why is this? Well. Mhm. One possibility is that there there may be a delay in diagnosis and women um uh and therefore treatment because there's a lack of diagnostic criteria that accounts for body size. So women, even when accounting for body surface area, still have smaller hearts than men. and to use a universal diagnosis of 1.5 cm as a diagnostic criteria for Hypertrophic cardiomyopathy may create a situation where women have much more advanced disease by the time they reached at 1.5 centim threshold than men. And certainly um this all leads to poor outcomes. So this study um can't study almost 1000 patients from Italy and two locations in the U. S. The Minneapolis Heart Institute in the Tufts New England Medical Center. And um it is notable, it's not in the charter, but it's notable that this cohort, a woman um were older by nine years um than men at time of diagnosis, and they were much more symptomatic um when engaged by the new york Art association class and women are more likely to have um left ventricular outflow tract obstruction at time of diagnosis. And in the mean you follow up here a little over six years, um woman has significantly higher rate of progression to severe heart failure and death um from heart attack or stroke. So this is um this is not a good news for woman with hypertrophic cardiomyopathy. Um here is data from another study. Um this looked at 3600 patients from Mayo Clinic Rochester between 1975 and 2012. And interestingly enough, again, 45 women um not 50% 45 Um and patients were followed for um approximately 11 years um on average. And women again it's shown to have worse survival at 10 years. Um Woman um uh survival for women was 70% versus 82 for men. Um So what does this teach us? It teaches us moving forward, um We we're going to need more aggressive diagnostic evaluation and lower threshold of suspicions when it comes to hypertrophic cardiomyopathy. Um in addition to the delay, the an atomic consideration of the 1.5 centimeter for diagnostic criteria. Um There is some thought that there may be a protective effect of sex hormones, especially estrogen, that maybe confounding some of the delay in um disease progression and diagnosis. Um But for the most part um um the uh increased awareness that this can happen to women a much smaller acceptable things or just generally ventricular thickness. Um um is I think the key point today when it comes to um um our treatment of women with hypertrophic cardiomyopathy. Um Okay, so moving forward here with cardiomyopathy is associated with lupus. Here's a question for people to think about which is following medications for treatment of lupus and rheumatoid arthritis is associated with cardio toxicity and cardiomyopathy. A is a dia print be hydroxychloroquine. See michael finally. D riTUXimab. Well, answer this question in a little bit. So lupus is a chronic inflammatory disease of unknown cause combination of genetic susceptibility, environmental triggers and maybe viral. Um It's a multi organ disease obviously as um as we know skin joints, kidneys, lungs um central nervous system and of course the heart um and the clinical course is very variable. Um There may be there may be periods of remission um there may be a cure relaxes and um generally the pattern or the organ involvement that that dominates during the first few years of illness tend to prevail subsequently. Um And of course um this condition is relevant in today's talk because it disproportionately affects women. Um In the childbearing age, um women are affected 7-1 or two. Some estimates 15-1 um over men. So that is a huge tendency to um a huge disparity between the sexes and when it comes to disease um uh problems. So why is it more common in women? Well, there's some thought that there is a potential role of estrogen um that, you know, early monarchy hormone replace um or contraceptives, hormone replacement therapy um increases risk of lupus. Um that's a thought. Um uh even however, it must be more than that because even in Children uh pre pre people Children, um there's a female predominance. Um And then, so there is a belief there is some data to suggest that there there may be a X chromosome um gene variants that's contributing and the gene dose effect, which means because women have two X. Chromosomes versus men who have one X chromosome. Um We are more susceptible to developing this, developing this disease interestingly. Um Men um uh men who have X. X. Y. Um genetics. Klinefelter syndrome are actually 14% more likely to develop lupus than men with xy chromosomes. Um So overall bottom line is the incident is rising, prevalence is rising and this is something that as cardiologist. Um Well we will be seeing more of the cardiac complications of lupus. Um So this is just to illustrate that um cardiac complications of cardiac complications of lupus is very important to note. So here the cardiovascular disease event um represents stroke heart attack um and heart failure hospitalization. Um And um certainly um the um the uh the lupus cohort had nearly doubled mortality and cardiovascular disease event um hazards compared to age matched and even sex much comparison. So um important to note cardiovascular manifestations of this of this disease. Um So there's a long list of primary cardiovascular manifestations of lupus by far, when it comes to coronary disease. Atherosclerosis um is far more common than coronary vasculitis, thrombosis, or emboli when it comes to dawn coronary disease. Uh there's you can develop inflammatory by a card itis. Pericardial disease is the most common carding manifestation of lupus. Um. Um But um overall does not lead to significant heart failure risk in the long run valvular disease. We always hear about the non infectious um, lips and sacks endocarditis. We um but these are also not um uh common finding in lupus patients. Um Ray knots, um up to 40% of patients have it, but right now it is a relatively non specific finding that many patients, even without lupus can develop. Um And what's interesting about pulmonary hypertension and lupus is that vast majority of patients with pulmonary hypertension and lupus have pulmonary hypertension due to um CTF or chronic grambo am bolic pulmonary hypertension and not primary pulmonary arterial hypertension. Um So kind of honing into a few of these um um conditions. Um I want to focus on the skinny cardiomyopathy, the maya card eyes to a certain extent and the anti malarial associated cardiomyopathy. So it's me cardamom empathy is um a huge cost for more mortality and morbidity in lupus patients. Um In young women there is a 55-fold greater risk of coronary artery ischemic disease uh than um um Then um age matched um um age matched controls and angina and heart attack are most commonly due to atherosclerosis, as I mentioned earlier, not necessarily vasculitis or m. Bleier thrown by. This is my angiogram of one of our patients. Um At the time of um uh this angiogram patients um Was barely 50 years old, had not been diagnosed with Lupus quite yet. And and she really didn't have any other cardio risk factors. Um no family history and this is what we found. Um She was very thin, athletic, um had very good lifestyle habits. Um So having a high suspicion for coronary disease even in younger patients with lupus is really important. Um Second um my card itis um my cardio cardio tend to be more subclinical than acute foreman and mike arthritis and lupus patients and the uh frequent or chronic inflammation and fibrosis can lead to eventually very irreversible cardiomyopathy um and often can't mirror um times of general lupus flare. Um One interesting condition that we can see with um lupus patients um is um antimalarial associated cardiomyopathy. This is exceedingly rare. We think nobody really knows the true prevalence. I think based on a systemic review that was published in 2019. Um there were only two Upwards of 50 and most cases in literature of course there may be a lot of other community cases that are not being reported. But plaque we know is the brand new for hydro hydroxychloroquine. Oh um it's an anti malarial that's how it was developed but it's used in many different autoimmune diseases. Um here's a little um C. D. C. Um Um pamphlet about malaria and of course um you know a lot of people have been thinking about plaque you know um you know several months ago because of COVID-19. So the reason it's important to know this conditional is exceedingly rare because after all platform is a great drug for the treatment of many autoimmune diseases is because it can potentially be reversible. So this is one of our patients, 55 year old woman at the time of this presentation have been on chloroquine for um for three years. Was diagnosed with non ischemic cardiomyopathy. And her critical presentation included complete heart block and VP of arrest. And she received the I. C. D. And presented the scripts for a second opinion. And the thing about this condition is that it's it can only be diagnosed biopsy. So this is this is a biopsy and this is very classic for this condition. The large empty areas of vacuums without any inflammation is classic for this condition. Um And here on the electron microscope. Um those um curvilinear bodies which basically represent liposome. Oh dysfunction. Um so rare condition but potentially reversible. So good to be aware that this condition exists. And um should be referred to a uh place like scripts here where we have advanced heart failure clinic who can do the uh the appropriate diagnostics. Um So kind of um will kind of quickly go through these slides as I'm coming to an end of my time here. But a pair part of left ventricular non compaction and pericardial effusion. I included this. Um There are many different um really truly the whole spectrum of heart disease um deserves mention when it comes to um when it comes to management of pregnant patients. But I wanted to discuss this to patients at these two conditions because actually um they can often have a very benign course. Um so quickly left ventricle non compaction. It's actually more common in men and is thought to be an embryo logic um um um derangement that leads to this um cardiomyopathy. And it can be seen a lot of other associated disease like dilated cardiomyopathy, Hokum. Um And such um And yeah but it can also be seen in athletes hard and even pregnancy. So here we are. This is how you diagnose it on echocardiogram. You're just looking for a certain ratio of um my kardian that is um normal and not. And what's interesting is as general cardiologist we often get console for palpitation, Disney a and pregnant women and I believe doctor wouldn't use the same image as I did um in her talk. And what do we do? We often do echocardiogram an event monitor. They usually turn out just fine. But what's important is that um there was this this study came out that they looked at consecutive uh pregnant woman who didn't really have any underlying comorbidities. And it was notable for this um progressive trade regulation they saw throughout the course of the pregnancy, the result after delivery. So I think the learning point here is that oh and they think it's preloaded pendant doctor wouldn't also went over the aerodynamics of pregnancy earlier. But and so the thought here is that if you do see this, yes, it should be further evaluated but we do not have to jump. Um We don't have to the anxious or very worried that the patients suddenly has a dangerous life threatening cardiomyopathy. Or at least not yet. Um and does deserve further evaluation um and follow up. Um And similarly, um I recently saw a patient who has significant lightheadedness um and um and she was in her third trimester pregnancy and we found this per um pericardial effusion. It was at least moderate by size and what was interesting is that she was induced um And it resolved and there are very old, limited studies and literature that say that throughout pregnancy, pericardial effusion becomes actually very increasingly more common and tends to be benign and tends to resolve after delivery. And of course they do not come with pericarditis symptoms. So this was her, there is a 37 weeks, a couple of days later, she delivers and um it's almost all resolved and there is she is a four weeks post parliament, it's resolved and she's um she's gonna be having uh another pregnancy sooner, she's planning and I think she's good to do that. So in the last 30 seconds here, so we'll just kind of go over the last um topic, stress cardiomyopathy and outcomes. So I'll just kind of um this is a question, you know, what is false regarding stress cardiomyopathy? Um it's more common in women, poor outcome in women, older age of diagnosis of women and associated with increased incidents of hyperthyroidism. And we've all probably we are all aware of taco super cardiomyopathy. There's an increasing incidence um um in the last decade or two and um more um um research is being done in this field is thought to be related to the catacomb in search and my cardio stunning and often within a week this defect resolves um um there's quite a bit of in page in hospital mortality estimated as um Um as much as high as 2-4%. Um and as I mentioned, this is important because it is predominantly diagnosed woman. Um so despite the higher prevalence of woman, the interesting thing about talking civil cardiomyopathy is that um the mortality is hiring men and there may be association with men being younger and having um um having stress can dramatically more related to drug use um that has been noted in prior research and um and um the hypothyroidism was actually more common in women as well in this course. So that's an interesting area of research why although men are less likely to be affected, they tend to have higher mortality um at a younger age of onset, so more research to be done. And so yeah, basically um uh I hope this was relevant for your practice. Um and there are a lot of other good um talks and conferences about other cardiomyopathy um that here scripts we offer. So um okay, Thank you. Dr Kim. It's a little bit unfair what we did to Dr Kim. We gave her one of the most expansive largest topics and then we only give her 30 minutes. So I apologize if you felt rushed during that time, but I really, really appreciate you touching on those topics.