Podcasts about mitral valve prolapse

Today, we're going to talk about the #1 nutrient deficiency involved with mitral valve prolapse syndrome. If you have mitral valve prolapse, your heart valves are not opening and closing correctly. Mitral valve prolapse causes floppy, leaky valves that are large and bulging. This bulging, displaced tissue is called prolapse, which leads to inefficient heart pumping. Mitral valve prolapse symptoms include weakness, fatigue, palpitations, anxiety, and shortness of breath. It's often described as idiopathic, which means it has no known cause. Mitral valve prolapse is generally treated with beta-blockers or a calcium channel blocker. In a double-blind study, 141 subjects with mitral valve prolapse were compared to 40 healthy subjects. Sixty percent of the mitral valve prolapse group had magnesium deficiency compared to only 5% of the healthy subjects. Low magnesium leads to high adrenaline. It also accelerates the aging of the fibroblast cell, which helps you make collagen, elastin, and hyaluronic acid. As we age, the fibroblast cell is very important for our skin, ligaments, tendons, and valves. One of the first signs of magnesium deficiency is tetany. Surprisingly, 85% of people with mitral valve prolapse have tetany! Don't just rely on the RDA if you're deficient in magnesium. Try taking 400 mg 2 to 3 times a day, working up to this amount slowly. Also, ensure you're getting enough vitamin D. Magnesium won't work without vitamin D! Avoid sugar and refined carbs because they significantly decrease magnesium. It takes years for a magnesium deficiency to show up and it can take up to a year to correct. Try magnesium glycinate to increase your magnesium levels over time. DATA: https://www.ajconline.org/article/S00... https://pubmed.ncbi.nlm.nih.gov/3014234/ https://pubmed.ncbi.nlm.nih.gov/15945...

With David Duncker, Hannover Medical School, Hannover - Germany & Avi Sabbag, Chaim Sheba Medical Center, Ramat Gan - Israel. 

ESC TV Today brings you concise analysis from the world's leading experts, so you can stay on top of what's happening in your field quickly. This episode covers: Cardiology This Week: A concise summary of recent studies Peripartum cardiomyopathy Arrhythmogenic mitral valve prolapse Statistics Made Easy: The ‘Win Ratio' Host: Perry Elliott Guests: Carlos Aguiar, Johann Bauersachs and Kristina Haugaa Want to watch that episode? Go to: https://esc365.escardio.org/event/1138 Disclaimer This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC.   Declarations of interests Stephan Achenbach, Kristina Haugaa and Nicolle Kraenkel have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, AbbVie, Alnylam, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, Lilly, Novartis, Pfizer, Sanofi, Servier, Tecnimede. Johann Bauersachs has declared to have potential conflicts of interest to report: direct personal payment from healthcare industry: speaker fees, honoraria, consultancy, advisory board fees, investigator, committee member, etc. by Roche Diagnostics (Acute Heart Failure), Pfizer (Atrial Fibrillation), Bristol Myers Squibb (Atrial Fibrillation), Bayer (Chronic Heart Failure), Boehringer-Ingelheim (Chronic Heart Failure), Novartis (Chronic Heart Failure), CVRx (Chronic Heart Failure), AstraZeneca (Chronic Heart Failure), Cardior (Chronic Heart Failure), Norgine (Chronic Heart Failure). Research funding from healthcare industry under your direct/personal responsibility (to department or institution): Roche Diagnostics (Atrial fibrillation, co-investigator), Norgine (heart failure / iron deficiency, principal investigator), Zoll Medical (heart failure, co-investigator), CVRx (heart failure, investigator). Davide Capodanno has declared to have potential conflicts of interest to report: Sanofi, Novo Nordisk, Terumo, Medtronic. Perry Elliott has declared to have potential conflicts of interest to report: consultancies for Pfizer, BMS, Cytokinetics.  Emma Svennberg has declared to have potential conflicts of interest to report: institutional research grants from Bayer, Bristol-Myers, Squibb-Pfizer, Boehringer-Ingelheim, Johnson & Johnson, Merck Sharp & Dohme.

Commentary by Dr. Candice Silversides

Today's Episode Dr. Ravi Rao reviews case 34 from Medicine Morning Report: Beyond The Pearls. A 31-year-old female comes to your office to establish care. Her physical exam is normal with the exception of a midsystolic click that occurs just prior to a nonradiating grade 2 systolic murmur best heard over the apex. Today's Host Dr. Ravi Rao is a Cardiology Fellow at the University of California Riverside. About Dr. Raj Dr Raj is a quadruple board certified physician and associate professor at the University of Southern California. He was a co-host on the TNT series Chasing the Cure with Ann Curry, a regular on the TV Show The Doctors for the past 7 seasons and has a weekly medical segment on ABC news Los Angeles. More from Dr. Raj www.BeyondThePearls.net The Dr. Raj Podcast Dr. Raj on Twitter Dr. Raj on Instagram Want more board review content? Physiology by Physeo Step 1 Success Stories The InsideTheBoards Study Smarter Podcast The InsideTheBoards Podcast Study on the go for free! Download the Audio QBank by InsideTheBoards for free on iOS or Android. If you want to upgrade, you can save money on a premium subscription by customizing your plan until your test date on our website! Produced by Ars Longa Media To learn more about us and this podcast, visit arslonga.media. You can leave feedback or suggestions at arslonga.media/contact or by emailing info@arslonga.media. Produced by: Christopher Breitigan Executive Producer: Patrick C. Beeman, MD Legal Stuff InsideTheBoards is not affiliated with the NBME, USMLE, COMLEX, or any professional licensing body. InsideTheBoards and its partners fully adhere to the policies on irregular conduct outlined by the aforementioned credentialing bodies. The information presented in this podcast is intended for educational purposes only and should not be construed as professional or medical advice. Learn more about your ad choices. Visit megaphone.fm/adchoices

In this episode, we review the high-yield topic of Mitral Valve Prolapse from the Orthopedics section. Follow ⁠⁠⁠Medbullets⁠⁠⁠ on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbullets

#10 Paul Fasse shares his miracle story with Boots where he overcame hypertrophic obstructive cardiomyopathy, mitral valve prolapse, and myocardial bridging corrected in TWO open-heart surgeries at the Cleveland Clinic. The main theme in this episode is the importance of patient advocacy. Website: The Heart Chamber (theheartchamberpodcast.com)Transcript: Joyful Beat | The Heart Chamber (theheartchamberpodcast.com)The Heart Chamber (@theheartchamberpodcast)Thanks to Michael Moeri for being my right hand man. Michael Moeri - Audio Editor, Podcast Producer and Marketing Director

Take advantage of an exclusive podcast offer today by visiting http://www.invitehealth.com/podcast. For more information on the products or studies mentioned in this episode, as well as a complete transcript of the audio, click here.

Meet warrior, Tracy Riggs Frontz. Tracy is a professional, award-winning photographer and writer, mom, and newly married. As a child and teen, Tracy experienced many health issues such as reactive hypoglycemia, anxiety, depression, Mitral Valve Prolapse, and dysautonomia. In adulthood, she began to suffer with polycystic ovarian syndrome, restless leg syndrome, sleep apnea, fibromyalgia, bipolar type II, Sjogren's syndrome, type 2 diabetes, complex regional pain syndrome, hypermobility syndrome, major obesity, acid reflux, serotonin toxicity syndrome, osteoarthritis, PTSD, and high blood pressure. Tracy understands living with chronic illness and the stigmas that inevitably follow. She even created a blog to raise awareness called Spotlight on Stigma. Listen as Tracy discusses the positive or negative impact of these chronic illness stigmas and phrases. To learn more about Tracy including her writing or photography, you can visit www.NovelPhotos.com. To access her blog, go to her website and click on the Spotlight on Stigma header.

Thanksgiving is a day of mourning, consider: *learning about the tribes you land you live on- https://native-land.ca *donating to preserve Native American Heritage- https://www.naha-inc.org/donate/ It's time to continue the Chart of Fortune tradition of dedicating an episode to a dysfunctional family of reality tv. And this year it's time to pass the potatoes and stuffing and celebrate the Gotti-otti-otti-otti-otti-otti-otti-otti. Gotti family, blonde bangs, spiky hair, mob thangs. Yes, the 2004 A&E reality show Growing Up Gotti is getting an astrological recap. Did this show pave the way for RHONJ and Mob Wives? Does Victoria Gotti still have blond extensions (Ok, these are hypothetical questions but the answers are all yes). I'll also look at Victoria's chart and tell you how Randall Emmet, Lindsay Lohan and Mitral Valve Prolapse are related to this mob heiress and her children! Sources used in this episode https://www.youtube.com/watch?v=HrHpZ9NJd0M https://en.wikipedia.org/wiki/Victoria_Gotti https://en.wikipedia.org/wiki/Growing_Up_Gotti#Season_1_(2004) https://en.wikipedia.org/wiki/Carmine_Agnello https://theislandnow.com/uncategorized/gotti-house-in-old-westbury-raided-by-federal-agents/ https://thecinemaholic.com/victoria-gotti/ https://www.eonline.com/news/1013210/a-notorious-father-a-marriage-gone-wrong-and-a-whole-lot-of-loss-inside-victoria-gotti-s-life-in-her-own-words?query=gotti https://www.imdb.com/title/tt1801552/?ref_=tt_sims_tt_i_2 https://www.imdb.com/title/tt1801552/?ref_=tt_sims_tt_i_2 Podcast about outer planets and venus: https://theastrologypodcast.com/2016/02/28/the-outer-planets-and-relationships/ Gotti house tour 2016: https://www.youtube.com/watch?v=4I3VlAlZ6KQ

CardioNerds (Amit Goyal & Daniel Ambinder) join Oregon Health & Science University cardiology fellows (Miranda Merrill, Timothy Simpson, Kris Kumar, and Stacey Howell) for a riverside chat at the Portland waterfront! They discuss a case of cardiac arrest associated with mitral valve prolapse (MVP) with mitral annular disjunction (MAD). Dr. Punag Divanji provides the E-CPR and program director Dr. Hind Rahmouni provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident, Eunice Dugan, with mentorship from University of Maryland cardiology fellow Karan Desai.   Jump to: Patient summary - Case media - Case teaching - References Episode graphic by Dr. Carine Hamo The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary Coming soon! Case Media ABCDEFGClick to Enlarge A. CXRB. Rhythm Strips - ventricular fibrillationC. ECG: 1st degree AVB (PR ~ 215), borderline RAD, Qtc ~460 msec, slight ant. convexity with inferior terminal T waveD: TTE E: TTE with Pickelhaube Spike seen in mitral valve prolapse F-G: Cardiac MRI TTE 1 TTE 2 TTE 3 Cardiac MRI Episode Schematics & Teaching Coming soon! The CardioNerds 5! – 5 major takeaways from the #CNCR case Coming soon! References Coming soon! CardioNerds Case Reports: Recruitment Edition Series Production Team Bibin Varghese, MDRick Ferraro, MDTommy Das, MDEunice Dugan, MDEvelyn Song, MDColin Blumenthal, MDKaran Desai, MDAmit Goyal, MDDaniel Ambinder, MD

It’s the most common heart valve condition in the U.S., affecting around 8 million people: mitral valve prolapse. It’s also known as click-murmur syndrome or floppy valve syndrome. What are the symptoms? How serious is it? And how is it diagnosed? In this episode, Dr. Jonathan Fialkow explores this condition with cardiologist Socrates Kakoulides, M.D., medical director of the ambulatory diagnostic center at Miami Cardiac & Vascular Institute, part of Baptist Health South Florida.

This month on Episode 14 of the Discover CircRes podcast, host Cindy St. Hilaire highlights four featured articles from the July 3 and July 17 issues of Circulation Research. This episode also features an in-depth conversation with Dr. Brenda Ogle and Drs. Molly Kupfer and Wei-Han Lin regarding their study, In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid.     Article highlights:   Wei, et al. Palmitoylation Cycling and Endothelial Maturity   van Ouwerkerk, et al. Functional Variant Elements in Atrial Fibrillation Models   Ibarrola, et al.  Aldosterone in MVP   Sharma, et al. Atherosclerosis Regression Requires Regulatory T Cells   Cynthia St. Hilaire: Hi, welcome to Discover CircRes, the podcast of the American Heart Association's Journal, Circulation Research. I'm your host, Dr. Cindy St. Hilaire, from the Vascular Medicine Institute at the University of Pittsburgh. Today I'm going to share with you four articles selected from our July issues of Circulation Research, as well as have a discussion with Dr. Brenda Ogle and the first authors, Molly Kupfer and Wei-Han Lin, regarding their study, In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid. So first, the highlights. The first article I want to share with you is titled, "Endothelial Palmitoylation Cycling Coordinates Vessel Remodeling in Peripheral Artery Disease." The first author is Xiaochao Wei, and the corresponding author is Clay Semenkovich from Washington University, St. Louis. Peripheral artery disease, or PAD for short, is a vascular occlusive disease of the lower extremities. It affects more than 2 million individuals globally, and its prevalence is ever increasing as our population ages. While statin therapy can be useful for combating coronary artery disease in peripheral artery disease patients, it does not prevent or reduce PAD patients' rates of lower extremity amputation. So looking to gain insights into the mechanisms underlying PAD, this team focused on the findings that circulating fibronectin and the dietary saturated fatty acid, palmitate, are associated with peripheral artery disease. They found this interesting as lipid modification proteins has been implicated in infections, premature aging, cancer and diabetes. One such protein modification is palmitoylation, which is the formation of a thioester bond between palmitate sand cysteine. Acyl-protein thioesterase 1, or APT1, is a depalmitoylase enzyme, which removes the fatty acid palmitate from protein. Using mouse models with inactivated endothelial APT1, as well as cell systems in arterial samples from humans with end stage peripheral artery disease, they tested whether deficiencies in palmitoylation cycling promotes endothelial instability, which is a hallmark of chronic arterial occlusive diseases. They discovered that as many as 10% of all proteins are palmitoylated. They found deficiency of APT1 in endothelial cells disrupts vascular homeostasis, in part by altering the intracellular trafficking of the small GTPase R-Ras. Impaired R-Ras membrane trafficking was rescued by modifying the palmitoylated R-Ras molecule to promote dissociation from membranes. These observations identify palmitoylation cycling as a potential therapeutic target in the treatment of peripheral vascular disease. The second article I want to highlight is titled, "Identification of Functional Variant Enhancers Associated with Atrial Fibrillation." The first author is Antoinette van Ouwerkerk, and the corresponding authors are Antoine de Vries and Vincent Christoffels, And they're from UMC Amsterdam. As we heard in our podcast last month with our interview with Dr. David McManus, atrial fibrillation, or AFib, is the most common form of arrhythmia, and is a major risk for heart failure, dementia, and stroke, and sudden death. Genome-wide association studies have revealed more than a hundred genetic loci linked to this condition, and many of these loci are found in non-coding regions, which are enriched for transcription factor binding sites and epigenetic modification sites, suggesting that these loci could potentially have gene regulatory roles. To test this idea, they use the method called self-transcribing active regulatory region sequencing, or STARR-seq, which is a method used to identify the sequences that act as transcriptional enhancers in a direct quantitative and genome-wide manner. They use STARR-seq to screen 12 of the strongest AFib linked regions of the genome, which contain more than 1600 individual aphid linked genetic variance, and they did this in cultured rat atrial monocytes. From this screen, they found approximately 400 regulatory elements, of which 24 exhibited variant-specific differences in regulatory activity. For one of these elements, upstream of the gene HCN4, deletion of the orthologous element in mice caused diminished transcriptional activity of the gene. Moreover, these variant-containing mice had brachycardia and sinus node dysfunction, both components of arrhythmia. This proof of principle study confirms that such a regulatory element screen could provide insight into the consequences of variants associated with AFib, or for that matter, many other diseases. The next article I want to share with you is titled, "A New Role for the Aldosterone/Mineralocorticoid Receptor Pathway in the Development of Mitral Valve Prolapse." The first author is Jaime Ibarrola, and the corresponding author is Natalia López-Andrés, and their work was completed at Sanitaria de Navarra in Pamplona, Spain. Mitral valve prolapse is a condition where blood leaks back into the left atrium of the heart, and it is the most common form of heart valve defects. The underlying pathology includes an overabundance of cells in the valve leaflet, so-called valve interstitial cells, or VICs. These activated VICs overproduce extracellular matrix protein, and the combination of increased numbers of VICs and increased amounts of extracellular matrix proteins contributes to the impairment of the structural integrity of the valve leaflet. The increase in VICs is due to excess proliferation, but also transformation of valve endothelial cells, so the cells that line the leaflet, valve endothelial cells, into mesenchymal like VICs. As a driver of endothelial to mesenchymal transition, aldosterone was suspected to play a role. Aldoesterone increased expression of VIC activation markers in cultured valve endothelial cells and increased production of certain extracellular matrix protein components. Spironolactone, an aldosterone inhibitor, prevented these effects, and importantly, prevented valve remodeling in a mouse model of mitral valve prolapse. The team showed that valve tissue from mitral valve prolapse patients taking aldosterone receptor inhibitors displayed less evidence of VIC activation and lower production of disease-regulated extracellular matrix components, than those not taking the drugs. These exciting results suggest aldosterone antagonists, already used for certain patients with heart failure or high blood pressure, may also benefit those with mitral valve prolapse. The last article I want to share before we switch to our interview, is titled, " Regulatory T Cells License Macrophage Pro-Resolving Functions During Atherosclerosis Regression." The first author is Monika Sharma, and the corresponding author is Kathryn Moore, and they're from New York University. Atherosclerosis is a chronic inflammatory condition characterized by the buildup of fatty deposits in the artery walls, and monocytes and macrophages can infiltrate into these fatty deposits and contribute to the formation of plaque. Cholesterol-lowering drugs, like statins, promote the reduction of low-density lipoproteins in the blood, which can help to slow plaque growth, but they do not reverse disease progression. One possibility for changing the course of the disease is to develop therapies that can reduce plaque inflammation, and therefore, progression. With that goal in mind, this team investigated how the immunosuppressive activity of regulatory T cells, or Tregs, may influence the functions of plaque monocytes and macrophages. Using mouse models in which the disease can be reversed through aggressive lipid lowering, they found that depletion of the Treg population caused an increase in the numbers of monocytes and macrophages in the plaques, and resulted in poorer plaque regression. Indeed, these monocytes and macrophages proliferated more, remained in the plaques longer, and were less likely to adopt an anti-inflammatory pro-plaque resolving M2-like phenotype than plaque macrophages in mice with normal Treg numbers. Together, these results highlight the importance of Tregs for promoting plaque regression, and suggest future therapies aimed at boosting these cells, or indeed, M2 macrophages may enable atherosclerosis remission. Okay, so now we're going to switch over to the interview portion of our podcast. I have with me Dr. Brenda Ogle, who is a professor of biomedical engineering, and first authors Molly Kupfer and Wei-Han Lin, and they're from the University of Minnesota. And today we're going to be discussing their manuscript titled, "In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid." So thank you all for joining me today.   Brenda Ogle: Thank you. Molly Kupfer: Thanks for having us. Wei-Han Lin: Thank you. Cynthia St. Hilaire: Great. I'm glad we can all do this remotely and nice and safe for COVID. So Dr. Ogle, you're the PI of the group, but Molly and Wei-Han, what stages of career are you at? Molly Kupfer: I just recently completed my PhD, so this work is sort of the culmination of that. Cynthia St. Hilaire: Oh, congratulations! Molly Kupfer: Yeah. Thank you. Cynthia St. Hilaire: Well done. Circ Research is a great thesis publication. Congratulations. Molly Kupfer: Thank you. Cynthia St. Hilaire: Wei-Han, how about you? Wei-Han Lin: So I'm a BME PhD student at the University of Minnesota. And I got my master degree in chemical engineering, but in Taiwan, and now I'm working with professor Brenda Ogle on cardiac tissue engineering stuff. Cynthia St. Hilaire: Excellent. So this is a beautiful paper. It's stunning. It has all sorts of wonderful parts, biological, biomechanical, great imaging, and essentially you created a 3D bio-ink that can be used to print and make a living pump, kind of a heart in a dish. And it's something that you're calling this human chambered muscle pump, or ChaMP, which I think is a great name. Can you please describe exactly what that is and why did you want to go about trying to make it? Molly Kupfer: Yeah, it might help if I give a little bit of context to this. So since the beginning, one of the central questions that the lab has been exploring is how do the cells of the heart interact with their environment, or the extracellular matrix, as we call it? We know that these interactions that occur at the cellular level are absolutely critical for cardiac function, both at the tissue and the organ level. And based on years of research studying how the extracellular environment modulates cellular function, we have now sought to apply what we've learned in order to engineer functional human cardiac tissues by recapitulating those very critical interactions in vitro. And actually, back in 2017, we published another study in Circulation Research, where we generated these contractile patches of cardiac tissue using a form of light-based 3D printing that allowed us to fabricate scaffolds with really high resolution micron-level features that were distributed in a way that mimics the native extracellular environment. And what we found is that by organizing the extracellular matrix in that way, we enabled the cells to organize themselves in the scaffold and form connections with each other and with the scaffold itself. And this was critical to achieving synchronous electromechanical function of the tissue as a whole. But these were very small millimeter scale tissues, and so for this new study, we sought to create something on a larger scale where you could incorporate some new geometric features such as chambers and the capacity for perfusion. And as you mentioned, using our knowledge of the interactions between cells and the extracellular matrix, we developed this unique bio-ink that could be used as a vehicle to 3D print these centimeter scale chambered tissue structures that are based on the geometry of the human heart. And so the tissues that resulted from this, the human chambered muscle pumps, or hChaMPs, exhibit thick, contiguous muscularization. They demonstrate electrical connectivity and pump function. And notably, this is the first time that this level of function and muscularization has been achieved in an engineered cardiac tissue of this level of geometric complexity. Cynthia St. Hilaire: So can you maybe talk a little bit about what do you mean by an ink, exactly? Is it actually printed? Is this like a printer that I could buy on Amazon? Obviously there's a huge biological component, but what are the actual technical things that you had to develop to make this chamber happen?  Molly Kupfer: Yes. So we did use an extrusion-based 3D printing, which is similar to probably what people normally think about with 3D printing. Traditionally, it's been with plastics. In this case, we're printing with a bio-ink, which is essentially a formulation of proteins and other materials that we encapsulate the cells in, and then after that, we extrude it from a nozzle in a specific formulation or shape in order to create the structure. Cynthia St. Hilaire: So that's interesting. So in this mix, the cells are already in there as opposed to, I guess, some other things that people tend to call scaffolds where you kind of print that and then seed it?  Molly Kupfer: Mm-hmm (affirmative). And in the example of the paper I discussed from 2017, that was an example where we printed a scaffold and put the cells in. But in this case, for such a large and complex structure, we actually mix the cells in prior to printing, and then we create the structure. Cynthia St. Hilaire: Wow. What's the timeframe of that? Like the cells, you got to digest them and mix things up and then print it. The cells, are they happy?  Molly Kupfer: Yeah, that's a good question. So the actual printing process is quite fast, maybe a couple of minutes for this particular scale. We have to prepare, culture, the cells in advance and we're working with human-induced, pluripotent stem cells, so it takes time to grow them up, and then yes, we do detach them and singularize them, and we then mix them with the components. But overall, the actual printing process is relatively quick. Then it's a matter of maintaining the structure and culturing it and doing the differentiation as we did. And that takes weeks to do over time. But the actual process of making it, initially, is quite quick. Brenda Ogle: Challenging thing about this project was the fact that mature cardiac muscle does not transfer well. Meaning when you move it from a dish to an ink and then print it and ask it to start beating again, it doesn't typically happen. And that is because cardiomyocytes don't proliferate well, or make more of each other, and they also don't move well, or migrate. And so the premise on which most of this paper relies is on printing the stem cells first, letting them expand, sort of like they do with development, and then encouraging them to specify into cardiac cell types. Cynthia St. Hilaire: What's the bigger good that can come out of this? Why do we want to be able to do this in vitro, or even ex vivo heart in a dish? Brenda Ogle: The value is pretty tremendous because, suddenly we have a human model system in which we can perfuse volume, so volume can go in and come out, in which the cells experience those volume metric and fluid-induced forces that we haven't been able to study human cells in this way ever before. In the context of human disease, this is the first time we'll be able to look at onset of a particular disease, what was happening with onset, and then progression. And I think that is what is going to transform this field. Cynthia St. Hilaire: So what was the first one like? I'm thinking back to my graduate school and also my postdoc where I was involved in some disease discovery and I have a very vivid memory of the Western blot that proved the mutation that we found. And I literally ran down the hall holding the film. I'm imagining, maybe I'm projecting too much, but what was seeing that first one beat like? Molly Kupfer: You're not projecting. I feel like that well describes my experience. We had some early experiences where we would start to see beating areas under the microscope, but I think the moment, for me, was, I think there was one night I was working in the lab and I had some plates out, I was looking at stuff under the microscope going through just the mundane lab tasks, and I think I sort of saw it at the corner of my eye in the dish, something was moving. And that was the first time. Like I had watched parts of these things beat under a microscope all the time. I spent years looking at cardiomyocytes under a microscope, but that was the first time, for these hChaMPs, where I could actually see it moving just by my eye. Cynthia St. Hilaire: Wow. Molly Kupfer: And that was a really cool moment. Wei-Han Lin: Yeah. I was mostly working on the printing side, so the first time I realized the heart started beating, it's more like a shock to me, because I'm always printing the models or just the mold. But then really seeing those cells, or the whole structure, start to beat, was quite amazing.   Cynthia St. Hilaire: Could you please tell me a bit about the 3D printing aspect of it? Is it like a shell like the outside of a balloon, or does it have an interior structure that helps dictates where the cell go? Can you explain what the printing is? Wei-Han Lin: So the structure we are printing is derived from MRI image stacks on a real human heart. And the image stack was segmented and reduce the size by 10 times, and then we convert the stack into the STL file, which is the standard operating format. And then we modify the model a little bit to make it into two chambers and with two vessels, and two connected chambers with two openings. And this is the heart we are using for the study. Cynthia St. Hilaire: Got it. So it's got kind of the big picture items of the heart. It's got two tubes going in and it's got two chambers and the fluid can flow between all of those aspects in a specific flow pattern. Wei-Han Lin: Exactly. Cynthia St. Hilaire: You said you have to differentiate them in a dish and you're adding different factors to do that. Do the cells like being in that scaffold, or do they want to seep out of that structure or is there something about the bio-ink that they're happy there? Molly Kupfer: You know, I think this bio-ink was, to a certain extent, optimized or designed such that the cells would be able to continue to attach and grow and remodel. So basically, for the most part, these components are biological materials. Some of them are just proteins. Some of them are proteins that have been modified with photo cross-linkable elements, but they still have these moieties that the cells can attach to. And over time we do see some remodeling and some extracellular matrix gets degraded and some gets deposited. Cynthia St. Hilaire: So have you gone to the next steps of something like single cell seq and trying to see what kind of cells you're getting in this? Or even maybe inputting different, the scaffold is getting one differentiation protocol, but are you possibly able to prime IPS cells such that they're maybe halfway to a vascular cell, or halfway to a cardiomyocyte cell, and then put them in the bio-ink? Brenda Ogle: That's a really interesting idea. I'm going to take that one. Cynthia St. Hilaire: Give me an acknowledgment. Brenda Ogle: So we've been thinking about that, the context of if expansion of IPS cells is the best way, for many cell types, how do we get multiple cell types and organize them? And you can imagine even just printing in specific areas, different cell types. Cynthia St. Hilaire: Oh, sure. Brenda Ogle: But the other thing we've thought about is delivering differentiation factor spatially. So almost printing a cell, but then printing that. depot of a factor, in the area that we wanted or in an arrangement that we want, and then releasing it when we want. And it's challenging for stem cell differentiation, because you really need no release, and then basically zero order release for two or three days, and then no release again. Cynthia St. Hilaire: Right. Brenda Ogle: So it's a challenging drug delivery problem, but we've been thinking a lot about it. Now priming the cells beforehand is another interesting approach. Cynthia St. Hilaire: Well, that's wonderful. I just want to congratulate you all again. Brenda Ogle: Thank you so much for having us. Cynthia St. Hilaire: Yeah, thank you so much. Wei-Han Lin: Thank you so much. Cynthia St. Hilaire:  That's it for our highlights from the July issues of Circulation Research. Thank you so much for listening. Please check out the Circulation Research Facebook page and follow us on Twitter and on Instagram with the handle @CircRes and #discovercircres. Thank you to our guests, Dr. Brenda Ogle, Dr. Molly Kupfer and Wei-Han Lin. This podcast is produced by Rebecca McTavish and Ishara Ratnayake, edited by Melissa Stoner and supported by the editorial team of Circulation Research. Some of the copy texts for highlighted articles was provided by Ruth Williams. I'm your host Dr. Cindy St. Hilaire, and this is Discover CircRes, you're on the go source for the most up-to-date and exciting discoveries in basic cardiovascular research.  

Interview with Lakshmi Muthukumar, MD, and Arshad Jahangir, MD, authors of Association Between Malignant Mitral Valve Prolapse and Sudden Cardiac Death: A Review, and Marc Andrew Miller, MD, and David Adams, MD, authors of Hybrid Positron Emission Tomography/Magnetic Resonance Imaging in Arrhythmic Mitral Valve Prolapse

Interview with Lakshmi Muthukumar, MD, and Arshad Jahangir, MD, authors of Association Between Malignant Mitral Valve Prolapse and Sudden Cardiac Death: A Review, and Marc Andrew Miller, MD, and David Adams, MD, authors of Hybrid Positron Emission Tomography/Magnetic Resonance Imaging in Arrhythmic Mitral Valve Prolapse

Listen as Dr. London Smith (.com) and his producer Cameron discuss Mitral Valve Prolapse with special guest Pilgrim. Not so boring! Hosts: London Smith, Cameron Clark Guest: Aaron Minton. Produced by: Dylan Walker Created by: London Smith

Jane Ferguson:  Hi, everyone. Welcome to Getting Personal: Omics of the Heart, the podcast from Circulation: Genomic and Precision Medicine. It's May 2019, and this is episode 28. So let's see what papers we have in the journal this month.                              First up, a paper from Mengyao Yu, Nabila Bouatia-Naji and colleagues from the Inserm Cardiovascular Research Center in Paris, entitled GWAS-Driven Gene-set Analyses, Genetic and Functional Follow-Up Suggest Glis1 as a Susceptibility Gene for Mitral Valve Prolapse.                              In this paper, they set out to characterize the genetic contributions to mitral valve prolapse, or MVP, to better understand the biological mechanisms underlying disease. They applied the gene-set enrichment analysis for QWAS tool and the pathway enrichment tool DEPICT to existing GWAS for MVP in a French sample to identify gene sets associated with MVP. They find significant enrichment of genes involved in pathways of relevance to valve biology and enrichment for gene expression in tissues of relevance to cardiovascular disease.                              They zeroed in a Glis family zinc finger gene Glis1 with consistently strong pattern of evidence across the GWAS enrichment and transcription analyses. They replicated the association between Glis1 and MVP in a UK biobank sample. They found that Glis1 is expressed in valvular cells during embryonic development in mice, but is mostly absent at later times. They targeted two Glis1 orthologs in zebrafish and found that knockdown of Glis1 B was associated with a significant increase in the incidence of severe atrioventricular regurgitation. These data highlight Glis1 as a potential regulator of cardiac valve development with relevance for risk of mitral valve prolapse.                              Next up is a paper from Gina Peloso, Akihiro Namuro, Sek Kathiresan and colleagues from Boston University, Kanazawa University, and Mass General Hospital. In their paper, Rare Protein Truncating Variance in APOB, Lower LDL-C, and Protection Against Coronary Heart Disease, the team was interested in understanding whether protein truncating variance in APOB underlying familial hypobetalipoproteinemia confer any protection against coronary heart disease.                              They sequenced the APOB gene in 29 Japanese families with hypobetalipoproteinemia as well as in over 57,000 individuals, some with early onset CHD and some without CHD. They found that presence of an APOB truncating variant was associated with lower LDL cholesterol and lower triglycerides, and also with significantly lower risk for coronary heart disease. This study confirms that variance in APOB, leading to reduced LDL and triglycerides are also protective against coronary heart disease. :                            The next paper entitled Mortality Risk Associated with Truncating Founder Mutations in Titin comes to us from Mark Jansen, Dennis Dooijes, and colleagues from University Medical Center Utrecht. They analyzed the effect of titin truncating variance on mortality in Dutch families. Titin truncating variants are associated with dilated cardiomyopathy, but have a very variable penetrance.                              In this study, the authors looked at three titin truncating variants, established to be founder mutations, and traced the pedigrees back to 18th century ancestors. They looked at 61 individuals on the transmission line and 360 of their first-degree relatives. They find no evidence for excess mortality in variant carriers overall. However, when they restrict it to individuals over 60 years of age, they did find a significant difference in mortality, which was also observed in individuals born after 1965. What these data tell us is that these titin truncating variants have a relatively mild phenotype with effects on mortality only manifesting later in life in many carriers. Given increases in life expectancy over the past several decades, the prevalence of morbidity and mortality attributable to titin truncating variants may increase. Genetic screening may identify genotype-positive, phenotype-negative individuals who would benefit from preventative interventions.                              Continuing on the theme of genetic variance, we have a paper from John Giudicessi, Michael Ackerman, and colleagues from the Mayo Clinic, Assessment and Validation of a Phenotype-Enhanced Variant Classification Framework to Promote or Demote RYR2 Missense Variants of Uncertain Significance. In this paper, they aim to find a better way to classify variants of unknown significance, of VUS, in the RYR2 gene. Variants in this gene are commonly associated with catecholaminergic polymorphic ventricular tachycardia, or CPVT.                              They examined 72 distinct variants in 84 Mayo Clinic cases and find that 48% were classified as VUS under ACMG guidelines. The rate was similar in a second sample from the Netherlands, with 42% of variants originally classified as VUS. They developed a diagnostic scorecard to incorporate a pretest clinical probability of CPVT, which included various clinical criteria, including symptoms and stress test results. Application of the phenotype enhanced ACMG criteria brought the VUS rate down to 7% in Mayo Clinic and 9% in the Dutch samples. The majority of VUS were reclassified as likely pathogenic.                              This study highlights how incorporation of disease-specific phenotype information can help to improve variant classification and reduce the ambiguity of reporting variants of unknown significance.                              We also have a number of research letters in the journal this month. From Karine Ngoyen, Gilbert Habib, and coauthors from Marseilles, we have a paper entitled Whole Exome Sequencing Reveals a Large Genetic Heterogeneity and Revisits the Causes of Hypertrophic Cardiomyopathy, Experience of a Multicentric study of 200 French Patients. In this study, they examined the genetic contributions to hypertrophic cardiomyopathy, or HCM, in 200 individuals as part of the HYPERGEN study and compared the benefits of whole exome sequencing compared with targeted sequencing of candidates' sarcomeric genes. All subjects had HCM documented by echocardiography.                              In the whole exome sequencing data, they first looked for mutations within 167 genes known to be involved in cardiomyopathies or other hereditary diseases. Of these 167 virtual panel genes, they find variants in 101 genes. Following whole exome sequencing, over 87% of the patients had an identified pathogenic, or likely pathogenic, mutation compared with only 35% of patients who only had targeted sequencing of sarcomeric genes.                              This highlights the generic heterogeneity of HCM and suggests that whole exome sequencing has utility in identifying variants not covered by sarcomeric gene panels.                              The next letter is from Wouter Te Rijdt, Martin [Vandenberg] and colleagues from University Medical Center Groningen and states that [dissynchronopathy] can be a manifestation of heritable cardiomyopathy. They hypothesized that left bundle branch block, also designated as dissynchronopathy, may be a manifestation of familial cardiomyopathy.                              They analyzed patients from a database of cardiac resynchronization therapy and identified super-responders whose left ventricular dysfunction was normalized by therapy. They carried out targeted sequencing in 60 known cardiomyopathy genes in 16 of these super-responder individuals and identified several variants, including a pathogenic variant in troponin T in one individual and variants of unknown significance in nine individuals. Pedigree analysis identified multiple family members with dilated cardiomyopathy.                              This study highlights that dissynchronopathy can be a manifestation of DCM, but that affected individuals may still benefit from cardiac resynchronization therapy.                              The next letter entitled Targeted Long-Read RNA Sequencing Demonstrates Transcriptional Diversity Driven by Splice-Site Variation in MYBPC3 comes from Alexandra Dainis, Euan Ashley, and colleagues from Stanford University. They set out to understand whether transcriptome sequencing could improve the diagnostic yield over genome sequencing in patients with hypertrophic cardiomyopathy. In particular, they hypothesized that long-read sequencing would allow for identification of alternative splicing linked to disease variance. They used long-read RNA and DNA sequencing to target the MYBPC3 gene in an individual with severe HCM who carried a putative splice-site altering variant in the gene. They were able to obtain heart tissue for sequencing and included several HCM and control subjects in addition to the patient with the MYBPC3 variant.                              They identified several novel isoforms that were only present in the patient sample, as well as some additional isoforms, including retained introns, extended exons, and an additional cryptic exon, which would not have been predicted based on the DNA variant. While the effects on protein function is not known, the transcripts are predicted to be translated.                              This analysis highlights the effect of a rare variant on transcription of MYBPC3 and provides additional evidence to link the variant to disease. This is a really nice approach, which could be used to probe causality and mechanisms, not only for cardiovascular disease, but for other rare variants in many disease settings.                              We finish with a perspective piece from Nosheen Reza, Anjali Owens, and coauthors from the University of Pennsylvania entitled Good Intentions Gone Bad, The Dangers of Sponsored Personalized Genomics. They present a case of a 23-year-old woman who presented for genetic counseling and evaluation after discovering she carried a likely pathogenic MYH7 variant associated with cardiomyopathy. She had no significant medical history, but had participated in employer-sponsored genetic testing motivated to identify potential variants related to cancer given a family history of cancer.                              After receiving her results, she experienced considerable anxiety and stopped exercising out of fear of cardiac complications. She visited an ER after experiencing chest pain, something she had not experienced previously. There was no appropriate counseling available at her institution for her genetic test results, leading her to seek out the additional counseling. Thus, while she was initially motivated to complete genetic testing because her employer offered it free of change, she ended up incurring costs related to the followup evaluation and counseling. Ultimately, she had no significant clinical findings. Although the variant had been listed as likely pathogenic, other sources consider it to be of unknown significance.                              This story highlights the psychological and financial impact that genetic testing can have on individuals, particularly when carried out without any pretest counseling or accessible post-test support when variants are identified.                              Despite the considerable promise of personalized medicine, there are many complexities to be considered, particularly with direct-to-consumer testing and employer-sponsored testing. This perspective highlights the ethical considerations and urges caution to maintain the best interests of patients.                              That's all for this month. Thanks for listening. I look forward to bringing you more next month.                              This podcast was brought to you by Circulation Genomic and Precision Medicine and the American Heart Association Council on Genomic and Precision Medicine. This program is copyright American Heart Association 2019.  

In this episode 26, I talk about how and why HSPs are more sensitive to caffeine than others. I also touch on the effects of other drugs as well as a possible connection to Mitral Valve Prolapse and HSP. I know--crazy. If you like the podcast, please leave a positive review on iTunes! Sign up for the weekly newsletter to be notified of the latest blog posts, podcast episodes, and HSP news. Resources mentioned in this episode: Dr. Elaine Aron "Coping Corner: Strengthening Your Decisions Through "Cardiac Exercise" Caffeine and Anxiety from stressbusting.co.uk Caffeine and shaking hands from Livestrong Mitral valve prolapse information Related posts on highlysensitiveperson.net: A connection between caffeine, Mitral Valve Prolapse, and high sensitivity? Sensitive to Caffeine: It’s my Kryptonite  Podcast music attribution: By the Coast (2004) (Antony Raijekov) / CC BY-NC 2.5

Mitral Valve Prolapse - Integrative Medial Approaches

Should most of the power of governance be with the States or the Federal government? What did our founding fathers intend when they wrote the US Constitution? Does the Federal government have too much power today? This week’s show will discuss these topics and will also include the second half of our interview with Wes King; a young conservative … Read more about this episode...

An examination of the heart sounds associated with midsystolic click. Midsystolic click is virtually synonymous with prolapse of the mitral valve toward the left atrium during systole.

Guest: Matthew Sorrentino, MD Host: Larry Kaskel, MD Did mitral valve prolapse kill the marathon runner in Chicago? In this segment Dr. Larry Kaskel talks to Dr. Matthew Sorrentino about Mitral Valve Prolapse. Is it life threatening on its own? What about when mixed with dehydration? What should physicians inform their patients about living with mitral valve prolapse?