Podcasts about cardiovascular research foundation

In this episode of The Brave Enough Show, Dr. Sasha Shillcutt and Dr. Roxana Mehran discuss:  Stress and the physiological risks that is places on our bodies  How to process and remove the daily stress from your body  How to decrease stress, anxiety and poor sleep as risk factors for cardiovascular disease  How to reinvent yourself as a woman physician  Roxana Mehran, MD, is an internationally renowned interventional cardiologist and clinical research expert in the field of cardiovascular disease. She leads a globally-respected academic research center focused on designing and implementing randomized clinical trials, outcomes research projects, and high impact academic publications. She has served as principal investigator for numerous global studies, developed risk scores for bleeding and acute kidney injury, participates regularly in developing clinical guidelines, and has authored >1,500 peer-reviewed articles. Dr. Mehran currently serving as a member of the American College of Cardiology (ACC) Board of Trustees. She is a founder and Chief Scientific Officer of the Cardiovascular Research Foundation (CRF). Dr. Mehran is named Director of the Women Heart and Vascular Center at Mount Sinai Fuster Heart Hospital, spearheading a new program that represents a collaboration across multiple disciplines and designed to meet the unique needs of women's cardiovascular health. She has been included for the past seven consecutive years in Clarivate Analytics:  “Most Cited Researchers – Top 1%” as well as “The World's Most Influential Scientific Minds” (Thomson Reuters).   Dr. Mehran has spoken and attended over 400 presentations, leading the Lancet Commission on Women's Cardiovascular Diseases, which has brought together leading researchers from around the world to identify and bridge gaps in scientific discovery, clinical trials, and care for women with cardiovascular disease.  She was recently named Director of the Women Heart and Vascular Center at Mount Sinai Heart, spearheading a new program that represents a collaboration across multiple disciplines and designed to meet the unique needs of women's cardiovascular health. In 2019, she founded Women as One, dedicated to advancing opportunities for women in medicine.  Dr Mehran is a recipient of several awards including the 2016 American College of Cardiology Bernadine Healy Leadership in CV disease award, the 2018 Nanette Wenger Award from Women's Heart for excellence in research and education, the 2019 Ellis Island Medal of Honor, and the 2019 ESC Silver Medal and Andreas Grüntzig Lecture plaque. In 2022, she received The Terry Ann Krulwich Physician-Scientist Alumni Award at Mount Sinai; the Linda Joy Pollin Heart Health Leadership Award from Cedar Sinai Medical Center; Doctor Honoris Causa Degree at Università della Svizzera Italiana; Women in Cardiology Mentoring Award from American Heart Association; and the Pulse-Setter Champion Award from The Cardiovascular Research Foundation. Lastly, in 2023, Dr. Mehran was awarded the Bahr Award of Excellence by the American College of Cardiology.  Women as One Quote:  “We all need coaches to help us understand that if you are doing your best, whatever you accomplish in life is enough.” - Dr. Mehran  “Every time you are escalating and climbing the ladder as a woman, you have the responsibility to lift others in the process.” - Dr. Mehran  Episode Links:  BE24 Conference Invite Sasha to Speak Season 12 Sponsor - The Coach Firm The Coach Firm is a women-owned business that certifies life coaches in our signature method that focuses on mindset, coaching tools, and emotional regulation. Follow Brave Enough:   WEBSITE | INSTAGRAM | FACEBOOK | TWITTER | LINKEDIN Join The Table, Brave Enough's community. The ONLY professional membership group that meets both the professional and personal needs of high-achieving women.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/SPK865. CME/MOC/AAPA credit will be available until December 12, 2024.Addressing Unmet Needs in Anticoagulation for Thrombosis: Next-Generation Strategies for Improving Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from the Bristol Myers Squibb and Janssen Alliance.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerRoxana Mehran, MD, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Abbott; ABIOMED; Affluent Medical; Alleviant Medical; Amgen Inc.; AM-Pharma B.V.; Arena Pharmaceuticals, Inc.; AstraZeneca; AtriCure Inc.; Biosensors; BIOTRONIK SE & Co KG; Boston Scientific Corporation; Bristol Myers Squibb; CardiaWave; Celonova Biosciences Inc.; Chiesi USA, Inc.; Concept Medical; Cytosorbents Europe GmbH; Daiichi Sankyo Inc.; Duke; Element Science, Inc.; Faraday Pharmaceuticals; Humacyte, Inc.; Idorsia Pharmaceuticals Ltd; Janssen Pharmaceuticals, Inc.; Koninklijke Philips N.V.; Magenta Therapeutics; M.A. Med Alliance SA; MediaSphere Medical LLC; Medtelligence; Medtronic; MJH Life Sciences; Novartis Pharmaceuticals Corporation; OrbusNeich Medical Company Group Holdings Limited; Penumbra, Inc.; PhaseBio Pharmaceuticals, Inc.; Pi-Cardia; PLx Pharma Inc.; Protembis GmbH; RenalPro; RM Global Partners; Shockwave Medical Inc.; Vivasure Medical Limited; and ZOLL Medical Corporation.Honoraria from ACC (BOT Member, SC Member CTR Program) and JAMA Cardiology (Associate Editor).Stock Shareholder in Applied Therapeutics and Elixir Therapeutics, LLC.Other Financial or Material Support in the form of personal fees from Affluent Medical; Cardiovascular Research Foundation; Daiichi Sankyo Brasil; ER Squibb & Sons LLC; Esperion Therapeutics, Inc.; Europa Group/Boston Scientific Corporation; Gaffney Events Educational Trust; Ionis Pharmaceuticals; IQVIA Inc; J-CalC; McVeigh Global Meetings and Events; Novartis Pharmaceuticals Corporation; Novo Nordisk Inc.; Oversome; Primer Healthcare of New Jersey; Radcliffe Institute for Advanced Study; SL Solutions LLC; TARSUS Cardiology; Vectura Group Ltd; and Vox Media, LLC.Co-Chair/PlannerJeffrey Weitz, MD, FRCPC, FRSC, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alnylam Pharmaceuticals, Inc.; Bayer AG; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Daiichi Sankyo Co., Ltd.; Ionis Pharmaceuticals; Janssen Inc.; Merck & Co., Inc.; Pfizer; and Servier Canada.Honoraria from Ionis Pharmaceuticals; Janssen Inc.; Merck & Co., Inc.; Pfizer; and Servier Canada.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/SPK865. CME/MOC/AAPA credit will be available until December 12, 2024.Addressing Unmet Needs in Anticoagulation for Thrombosis: Next-Generation Strategies for Improving Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from the Bristol Myers Squibb and Janssen Alliance.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerRoxana Mehran, MD, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Abbott; ABIOMED; Affluent Medical; Alleviant Medical; Amgen Inc.; AM-Pharma B.V.; Arena Pharmaceuticals, Inc.; AstraZeneca; AtriCure Inc.; Biosensors; BIOTRONIK SE & Co KG; Boston Scientific Corporation; Bristol Myers Squibb; CardiaWave; Celonova Biosciences Inc.; Chiesi USA, Inc.; Concept Medical; Cytosorbents Europe GmbH; Daiichi Sankyo Inc.; Duke; Element Science, Inc.; Faraday Pharmaceuticals; Humacyte, Inc.; Idorsia Pharmaceuticals Ltd; Janssen Pharmaceuticals, Inc.; Koninklijke Philips N.V.; Magenta Therapeutics; M.A. Med Alliance SA; MediaSphere Medical LLC; Medtelligence; Medtronic; MJH Life Sciences; Novartis Pharmaceuticals Corporation; OrbusNeich Medical Company Group Holdings Limited; Penumbra, Inc.; PhaseBio Pharmaceuticals, Inc.; Pi-Cardia; PLx Pharma Inc.; Protembis GmbH; RenalPro; RM Global Partners; Shockwave Medical Inc.; Vivasure Medical Limited; and ZOLL Medical Corporation.Honoraria from ACC (BOT Member, SC Member CTR Program) and JAMA Cardiology (Associate Editor).Stock Shareholder in Applied Therapeutics and Elixir Therapeutics, LLC.Other Financial or Material Support in the form of personal fees from Affluent Medical; Cardiovascular Research Foundation; Daiichi Sankyo Brasil; ER Squibb & Sons LLC; Esperion Therapeutics, Inc.; Europa Group/Boston Scientific Corporation; Gaffney Events Educational Trust; Ionis Pharmaceuticals; IQVIA Inc; J-CalC; McVeigh Global Meetings and Events; Novartis Pharmaceuticals Corporation; Novo Nordisk Inc.; Oversome; Primer Healthcare of New Jersey; Radcliffe Institute for Advanced Study; SL Solutions LLC; TARSUS Cardiology; Vectura Group Ltd; and Vox Media, LLC.Co-Chair/PlannerJeffrey Weitz, MD, FRCPC, FRSC, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alnylam Pharmaceuticals, Inc.; Bayer AG; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Daiichi Sankyo Co., Ltd.; Ionis Pharmaceuticals; Janssen Inc.; Merck & Co., Inc.; Pfizer; and Servier Canada.Honoraria from Ionis Pharmaceuticals; Janssen Inc.; Merck & Co., Inc.; Pfizer; and Servier Canada.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/SPK865. CME/MOC/AAPA credit will be available until December 12, 2024.Addressing Unmet Needs in Anticoagulation for Thrombosis: Next-Generation Strategies for Improving Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from the Bristol Myers Squibb and Janssen Alliance.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerRoxana Mehran, MD, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Abbott; ABIOMED; Affluent Medical; Alleviant Medical; Amgen Inc.; AM-Pharma B.V.; Arena Pharmaceuticals, Inc.; AstraZeneca; AtriCure Inc.; Biosensors; BIOTRONIK SE & Co KG; Boston Scientific Corporation; Bristol Myers Squibb; CardiaWave; Celonova Biosciences Inc.; Chiesi USA, Inc.; Concept Medical; Cytosorbents Europe GmbH; Daiichi Sankyo Inc.; Duke; Element Science, Inc.; Faraday Pharmaceuticals; Humacyte, Inc.; Idorsia Pharmaceuticals Ltd; Janssen Pharmaceuticals, Inc.; Koninklijke Philips N.V.; Magenta Therapeutics; M.A. Med Alliance SA; MediaSphere Medical LLC; Medtelligence; Medtronic; MJH Life Sciences; Novartis Pharmaceuticals Corporation; OrbusNeich Medical Company Group Holdings Limited; Penumbra, Inc.; PhaseBio Pharmaceuticals, Inc.; Pi-Cardia; PLx Pharma Inc.; Protembis GmbH; RenalPro; RM Global Partners; Shockwave Medical Inc.; Vivasure Medical Limited; and ZOLL Medical Corporation.Honoraria from ACC (BOT Member, SC Member CTR Program) and JAMA Cardiology (Associate Editor).Stock Shareholder in Applied Therapeutics and Elixir Therapeutics, LLC.Other Financial or Material Support in the form of personal fees from Affluent Medical; Cardiovascular Research Foundation; Daiichi Sankyo Brasil; ER Squibb & Sons LLC; Esperion Therapeutics, Inc.; Europa Group/Boston Scientific Corporation; Gaffney Events Educational Trust; Ionis Pharmaceuticals; IQVIA Inc; J-CalC; McVeigh Global Meetings and Events; Novartis Pharmaceuticals Corporation; Novo Nordisk Inc.; Oversome; Primer Healthcare of New Jersey; Radcliffe Institute for Advanced Study; SL Solutions LLC; TARSUS Cardiology; Vectura Group Ltd; and Vox Media, LLC.Co-Chair/PlannerJeffrey Weitz, MD, FRCPC, FRSC, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alnylam Pharmaceuticals, Inc.; Bayer AG; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Daiichi Sankyo Co., Ltd.; Ionis Pharmaceuticals; Janssen Inc.; Merck & Co., Inc.; Pfizer; and Servier Canada.Honoraria from Ionis Pharmaceuticals; Janssen Inc.; Merck & Co., Inc.; Pfizer; and Servier Canada.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/SPK865. CME/MOC/AAPA credit will be available until December 12, 2024.Addressing Unmet Needs in Anticoagulation for Thrombosis: Next-Generation Strategies for Improving Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from the Bristol Myers Squibb and Janssen Alliance.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerRoxana Mehran, MD, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Abbott; ABIOMED; Affluent Medical; Alleviant Medical; Amgen Inc.; AM-Pharma B.V.; Arena Pharmaceuticals, Inc.; AstraZeneca; AtriCure Inc.; Biosensors; BIOTRONIK SE & Co KG; Boston Scientific Corporation; Bristol Myers Squibb; CardiaWave; Celonova Biosciences Inc.; Chiesi USA, Inc.; Concept Medical; Cytosorbents Europe GmbH; Daiichi Sankyo Inc.; Duke; Element Science, Inc.; Faraday Pharmaceuticals; Humacyte, Inc.; Idorsia Pharmaceuticals Ltd; Janssen Pharmaceuticals, Inc.; Koninklijke Philips N.V.; Magenta Therapeutics; M.A. Med Alliance SA; MediaSphere Medical LLC; Medtelligence; Medtronic; MJH Life Sciences; Novartis Pharmaceuticals Corporation; OrbusNeich Medical Company Group Holdings Limited; Penumbra, Inc.; PhaseBio Pharmaceuticals, Inc.; Pi-Cardia; PLx Pharma Inc.; Protembis GmbH; RenalPro; RM Global Partners; Shockwave Medical Inc.; Vivasure Medical Limited; and ZOLL Medical Corporation.Honoraria from ACC (BOT Member, SC Member CTR Program) and JAMA Cardiology (Associate Editor).Stock Shareholder in Applied Therapeutics and Elixir Therapeutics, LLC.Other Financial or Material Support in the form of personal fees from Affluent Medical; Cardiovascular Research Foundation; Daiichi Sankyo Brasil; ER Squibb & Sons LLC; Esperion Therapeutics, Inc.; Europa Group/Boston Scientific Corporation; Gaffney Events Educational Trust; Ionis Pharmaceuticals; IQVIA Inc; J-CalC; McVeigh Global Meetings and Events; Novartis Pharmaceuticals Corporation; Novo Nordisk Inc.; Oversome; Primer Healthcare of New Jersey; Radcliffe Institute for Advanced Study; SL Solutions LLC; TARSUS Cardiology; Vectura Group Ltd; and Vox Media, LLC.Co-Chair/PlannerJeffrey Weitz, MD, FRCPC, FRSC, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alnylam Pharmaceuticals, Inc.; Bayer AG; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Daiichi Sankyo Co., Ltd.; Ionis Pharmaceuticals; Janssen Inc.; Merck & Co., Inc.; Pfizer; and Servier Canada.Honoraria from Ionis Pharmaceuticals; Janssen Inc.; Merck & Co., Inc.; Pfizer; and Servier Canada.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/SPK865. CME/MOC/AAPA credit will be available until December 12, 2024.Addressing Unmet Needs in Anticoagulation for Thrombosis: Next-Generation Strategies for Improving Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from the Bristol Myers Squibb and Janssen Alliance.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerRoxana Mehran, MD, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Abbott; ABIOMED; Affluent Medical; Alleviant Medical; Amgen Inc.; AM-Pharma B.V.; Arena Pharmaceuticals, Inc.; AstraZeneca; AtriCure Inc.; Biosensors; BIOTRONIK SE & Co KG; Boston Scientific Corporation; Bristol Myers Squibb; CardiaWave; Celonova Biosciences Inc.; Chiesi USA, Inc.; Concept Medical; Cytosorbents Europe GmbH; Daiichi Sankyo Inc.; Duke; Element Science, Inc.; Faraday Pharmaceuticals; Humacyte, Inc.; Idorsia Pharmaceuticals Ltd; Janssen Pharmaceuticals, Inc.; Koninklijke Philips N.V.; Magenta Therapeutics; M.A. Med Alliance SA; MediaSphere Medical LLC; Medtelligence; Medtronic; MJH Life Sciences; Novartis Pharmaceuticals Corporation; OrbusNeich Medical Company Group Holdings Limited; Penumbra, Inc.; PhaseBio Pharmaceuticals, Inc.; Pi-Cardia; PLx Pharma Inc.; Protembis GmbH; RenalPro; RM Global Partners; Shockwave Medical Inc.; Vivasure Medical Limited; and ZOLL Medical Corporation.Honoraria from ACC (BOT Member, SC Member CTR Program) and JAMA Cardiology (Associate Editor).Stock Shareholder in Applied Therapeutics and Elixir Therapeutics, LLC.Other Financial or Material Support in the form of personal fees from Affluent Medical; Cardiovascular Research Foundation; Daiichi Sankyo Brasil; ER Squibb & Sons LLC; Esperion Therapeutics, Inc.; Europa Group/Boston Scientific Corporation; Gaffney Events Educational Trust; Ionis Pharmaceuticals; IQVIA Inc; J-CalC; McVeigh Global Meetings and Events; Novartis Pharmaceuticals Corporation; Novo Nordisk Inc.; Oversome; Primer Healthcare of New Jersey; Radcliffe Institute for Advanced Study; SL Solutions LLC; TARSUS Cardiology; Vectura Group Ltd; and Vox Media, LLC.Co-Chair/PlannerJeffrey Weitz, MD, FRCPC, FRSC, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alnylam Pharmaceuticals, Inc.; Bayer AG; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Daiichi Sankyo Co., Ltd.; Ionis Pharmaceuticals; Janssen Inc.; Merck & Co., Inc.; Pfizer; and Servier Canada.Honoraria from Ionis Pharmaceuticals; Janssen Inc.; Merck & Co., Inc.; Pfizer; and Servier Canada.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/SPK865. CME/MOC/AAPA credit will be available until December 12, 2024.Addressing Unmet Needs in Anticoagulation for Thrombosis: Next-Generation Strategies for Improving Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from the Bristol Myers Squibb and Janssen Alliance.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerRoxana Mehran, MD, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Abbott; ABIOMED; Affluent Medical; Alleviant Medical; Amgen Inc.; AM-Pharma B.V.; Arena Pharmaceuticals, Inc.; AstraZeneca; AtriCure Inc.; Biosensors; BIOTRONIK SE & Co KG; Boston Scientific Corporation; Bristol Myers Squibb; CardiaWave; Celonova Biosciences Inc.; Chiesi USA, Inc.; Concept Medical; Cytosorbents Europe GmbH; Daiichi Sankyo Inc.; Duke; Element Science, Inc.; Faraday Pharmaceuticals; Humacyte, Inc.; Idorsia Pharmaceuticals Ltd; Janssen Pharmaceuticals, Inc.; Koninklijke Philips N.V.; Magenta Therapeutics; M.A. Med Alliance SA; MediaSphere Medical LLC; Medtelligence; Medtronic; MJH Life Sciences; Novartis Pharmaceuticals Corporation; OrbusNeich Medical Company Group Holdings Limited; Penumbra, Inc.; PhaseBio Pharmaceuticals, Inc.; Pi-Cardia; PLx Pharma Inc.; Protembis GmbH; RenalPro; RM Global Partners; Shockwave Medical Inc.; Vivasure Medical Limited; and ZOLL Medical Corporation.Honoraria from ACC (BOT Member, SC Member CTR Program) and JAMA Cardiology (Associate Editor).Stock Shareholder in Applied Therapeutics and Elixir Therapeutics, LLC.Other Financial or Material Support in the form of personal fees from Affluent Medical; Cardiovascular Research Foundation; Daiichi Sankyo Brasil; ER Squibb & Sons LLC; Esperion Therapeutics, Inc.; Europa Group/Boston Scientific Corporation; Gaffney Events Educational Trust; Ionis Pharmaceuticals; IQVIA Inc; J-CalC; McVeigh Global Meetings and Events; Novartis Pharmaceuticals Corporation; Novo Nordisk Inc.; Oversome; Primer Healthcare of New Jersey; Radcliffe Institute for Advanced Study; SL Solutions LLC; TARSUS Cardiology; Vectura Group Ltd; and Vox Media, LLC.Co-Chair/PlannerJeffrey Weitz, MD, FRCPC, FRSC, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alnylam Pharmaceuticals, Inc.; Bayer AG; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Daiichi Sankyo Co., Ltd.; Ionis Pharmaceuticals; Janssen Inc.; Merck & Co., Inc.; Pfizer; and Servier Canada.Honoraria from Ionis Pharmaceuticals; Janssen Inc.; Merck & Co., Inc.; Pfizer; and Servier Canada.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/SPK865. CME/MOC/AAPA credit will be available until December 12, 2024.Addressing Unmet Needs in Anticoagulation for Thrombosis: Next-Generation Strategies for Improving Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from the Bristol Myers Squibb and Janssen Alliance.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerRoxana Mehran, MD, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Abbott; ABIOMED; Affluent Medical; Alleviant Medical; Amgen Inc.; AM-Pharma B.V.; Arena Pharmaceuticals, Inc.; AstraZeneca; AtriCure Inc.; Biosensors; BIOTRONIK SE & Co KG; Boston Scientific Corporation; Bristol Myers Squibb; CardiaWave; Celonova Biosciences Inc.; Chiesi USA, Inc.; Concept Medical; Cytosorbents Europe GmbH; Daiichi Sankyo Inc.; Duke; Element Science, Inc.; Faraday Pharmaceuticals; Humacyte, Inc.; Idorsia Pharmaceuticals Ltd; Janssen Pharmaceuticals, Inc.; Koninklijke Philips N.V.; Magenta Therapeutics; M.A. Med Alliance SA; MediaSphere Medical LLC; Medtelligence; Medtronic; MJH Life Sciences; Novartis Pharmaceuticals Corporation; OrbusNeich Medical Company Group Holdings Limited; Penumbra, Inc.; PhaseBio Pharmaceuticals, Inc.; Pi-Cardia; PLx Pharma Inc.; Protembis GmbH; RenalPro; RM Global Partners; Shockwave Medical Inc.; Vivasure Medical Limited; and ZOLL Medical Corporation.Honoraria from ACC (BOT Member, SC Member CTR Program) and JAMA Cardiology (Associate Editor).Stock Shareholder in Applied Therapeutics and Elixir Therapeutics, LLC.Other Financial or Material Support in the form of personal fees from Affluent Medical; Cardiovascular Research Foundation; Daiichi Sankyo Brasil; ER Squibb & Sons LLC; Esperion Therapeutics, Inc.; Europa Group/Boston Scientific Corporation; Gaffney Events Educational Trust; Ionis Pharmaceuticals; IQVIA Inc; J-CalC; McVeigh Global Meetings and Events; Novartis Pharmaceuticals Corporation; Novo Nordisk Inc.; Oversome; Primer Healthcare of New Jersey; Radcliffe Institute for Advanced Study; SL Solutions LLC; TARSUS Cardiology; Vectura Group Ltd; and Vox Media, LLC.Co-Chair/PlannerJeffrey Weitz, MD, FRCPC, FRSC, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alnylam Pharmaceuticals, Inc.; Bayer AG; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Daiichi Sankyo Co., Ltd.; Ionis Pharmaceuticals; Janssen Inc.; Merck & Co., Inc.; Pfizer; and Servier Canada.Honoraria from Ionis Pharmaceuticals; Janssen Inc.; Merck & Co., Inc.; Pfizer; and Servier Canada.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/SPK865. CME/MOC/AAPA credit will be available until December 12, 2024.Addressing Unmet Needs in Anticoagulation for Thrombosis: Next-Generation Strategies for Improving Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from the Bristol Myers Squibb and Janssen Alliance.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerRoxana Mehran, MD, has a financial interest/relationship or affiliation in the form of:Grant/Research Support from Abbott; ABIOMED; Affluent Medical; Alleviant Medical; Amgen Inc.; AM-Pharma B.V.; Arena Pharmaceuticals, Inc.; AstraZeneca; AtriCure Inc.; Biosensors; BIOTRONIK SE & Co KG; Boston Scientific Corporation; Bristol Myers Squibb; CardiaWave; Celonova Biosciences Inc.; Chiesi USA, Inc.; Concept Medical; Cytosorbents Europe GmbH; Daiichi Sankyo Inc.; Duke; Element Science, Inc.; Faraday Pharmaceuticals; Humacyte, Inc.; Idorsia Pharmaceuticals Ltd; Janssen Pharmaceuticals, Inc.; Koninklijke Philips N.V.; Magenta Therapeutics; M.A. Med Alliance SA; MediaSphere Medical LLC; Medtelligence; Medtronic; MJH Life Sciences; Novartis Pharmaceuticals Corporation; OrbusNeich Medical Company Group Holdings Limited; Penumbra, Inc.; PhaseBio Pharmaceuticals, Inc.; Pi-Cardia; PLx Pharma Inc.; Protembis GmbH; RenalPro; RM Global Partners; Shockwave Medical Inc.; Vivasure Medical Limited; and ZOLL Medical Corporation.Honoraria from ACC (BOT Member, SC Member CTR Program) and JAMA Cardiology (Associate Editor).Stock Shareholder in Applied Therapeutics and Elixir Therapeutics, LLC.Other Financial or Material Support in the form of personal fees from Affluent Medical; Cardiovascular Research Foundation; Daiichi Sankyo Brasil; ER Squibb & Sons LLC; Esperion Therapeutics, Inc.; Europa Group/Boston Scientific Corporation; Gaffney Events Educational Trust; Ionis Pharmaceuticals; IQVIA Inc; J-CalC; McVeigh Global Meetings and Events; Novartis Pharmaceuticals Corporation; Novo Nordisk Inc.; Oversome; Primer Healthcare of New Jersey; Radcliffe Institute for Advanced Study; SL Solutions LLC; TARSUS Cardiology; Vectura Group Ltd; and Vox Media, LLC.Co-Chair/PlannerJeffrey Weitz, MD, FRCPC, FRSC, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alnylam Pharmaceuticals, Inc.; Bayer AG; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Daiichi Sankyo Co., Ltd.; Ionis Pharmaceuticals; Janssen Inc.; Merck & Co., Inc.; Pfizer; and Servier Canada.Honoraria from Ionis Pharmaceuticals; Janssen Inc.; Merck & Co., Inc.; Pfizer; and Servier Canada.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

It's another session of CardioNerds Rounds! In these rounds, Dr. Karan Desai (Formerly FIT at University of Maryland Medical Center and currently faculty at Johns Hopkins School of Medicine) joins Dr. Dan Burkhoff (Director of Heart Failure, Hemodynamics and MCS Research at the Cardiovascular Research Foundation) to discuss mechanical circulatory support options through the lens of pressure-volume loops! Dr. Burkhoff is the author of Harvi, an interactive simulation-based application for teaching and researching many aspects of ventricular hemodynamics. Don't miss this wonderfully nerdy episode with a world-renowned expert in hemodynamics and MCS! Audio editing by CardioNerds Academy Intern, student doctor Chelsea Amo Tweneboah. This episode is supported with unrestricted funding from Zoll LifeVest. A special thank you to Mitzy Applegate and Ivan Chevere for their production skills that help make CardioNerds Rounds such an amazing success. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds. Case details are altered to protect patient health information. CardioNerds Rounds is co-chaired by Dr. Karan Desai and Dr. Natalie Stokes.  Challenging Cases - Atrial Fibrillation with Dr. Hugh Calkins CardioNerds Rounds PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Show notes - Hemodynamics and Mechanical Circulatory Support Case Synopsis: Case SynopsisWe focused on one case during these rounds. A man in his mid-50s presented to his local community hospital with 3 days of chest pain, nausea, and vomiting. He appeared ill in the emergency room with HR in the 150s, BP 90/70s and ECG demonstrating inferior ST elevations. He was taken emergently to the catheterization lab and received overlapping stents to his right coronary artery. Over the next 24 hours, he developed a new harsh systolic murmur heard throughout his precordium and progressed to cardiogenic shock. Echocardiogram demonstrated a large basal inferoseptum ventricular septal rupture. From this point, we discussed the hemodynamics of VSR and MCS options. Case Takeaways Dr. Burkhoff took us through the hemodynamics of VSR with pressure-volume loops to better understand the pathology and impact of various MCS options. Of note, there are no MCS devices specifically approved to treat acute ventricular septal rupture. In regards to the acute hemodynamic effects of a VSR (an abrupt left to right shunt), there are several aspects to note. First, the effective LV afterload is reduced; however, there is less “forward flow” as well and as a consequence, decreased left-sided cardiac output (“Qs”) and blood pressure. At the same time, flow through the pulmonary artery increases (the “Qp”). Additionally, due to the abrupt shunt flow, there is increased RV “loading” with increasing central venous pressure and pulmonary artery pressure. The hemodynamic priorities in treating patients with cardiogenic shock and VSR are to normalize blood pressure, cardiac output, and oxygen delivery, while attempting to minimize shunt flow to allow healing. However, medications and MCS are unlikely to completely normalize hemodynamics. For instance, if the patient was placed on peripheral VA ECMO, while total CO and BP may increase, flow across the VSR could also increase at high ECMO flows (e.g., by introducing more LV afterload). In patients with persistent cardiogenic shock and VSR, short-term MCS to divert flow away from the shunt can be an effective strategy. LV-to-aorta or LA-to-arterial MCS may provide the best single-device hemodynamic profiles by decreasing shunt flow, reducing pulmonary capillary wedge pressure, and improving blood pressure. Surgical and percutaneous VSD repair are the definitive treatment options. If able to stabilize patients and pursue delayed repair,

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 Interventional aspects of cardiogenic shock Diagnosis and management of tricuspid regurgitation Statistics Made Easy: Type I and Type II errors and their significance Host: Susanna Price Guests: Rebecca Hahn, Nicolle Kraenkel and Holger Thiele Want to watch that episode? Go to: https://esc365.escardio.org/event/898   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, Nicolle Kraenkel, Susanna Price and Holger Thiele 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, Alnylam, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, Lilly, Novartis, Pfizer, Sanofi, Servier, Tecnimede.  Davide Capodanno has declared to have potential conflicts of interest to report: Sanofi, Daiichi Sankyo, Terumo, Medtronic, Chiesi.  Rebecca Hahn has declared to have potential conflicts of interest to report: Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored tricuspid valve trials, for which she receives no direct industry compensation. 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.

This week, please join author Philipp Lurz and Editorialist Daniel Burkhoff as they discuss the article "Characteristics of Heart Failure With Preserved Ejection Fraction Across the Range of Left Ventricular Ejection Fraction" and the editorial "HF?EF: The Mysterious Relationship Between Heart Failure and Ejection Fraction Continues." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-host. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam: I just cannot wait to tell you about today's feature discussion, Greg. It's about heart failure with preserved ejection fraction and characteristics in the range of that ejection fraction that's above 50%. So, okay. I know, I know. It's like, "Oh my gosh. Wow. How much are we going to be talking about this ejection fraction thing?" But I'm telling you, everybody has to listen to this. It's really a big stride forward in our understanding of these patients with heart failure and a higher ejection fraction. Plus it includes one of my mentors from Mayo Clinic days, and I just can't wait for everyone to hear this. But before we go there, we've got really, really cool original papers in today's issue too. Would you like to start first? Dr. Greg Hundley: You bet Carolyn, and I can't wait for that feature discussion, especially this is a real area of your expertise. So listeners, hold on for that feature discussion. Well, my first paper, Carolyn, really pertains to physical activity. And Carolyn, the study is led by Dr. Don Hoon Lee from the Harvard T.H. Chan School of Public Health. And it evaluated a total of 116,000 adults from two large prospective US cohorts, the Nurse's Health Study and the Health Professional's Follow up Study that took place from 1988 to 2018. And they were examining self-reported leisure time physical activity and assessed the association between long term leisure time physical activity intensity and all cause and cause specific mortality. Dr. Greg Hundley: Now Carolyn, two types of physical activity were assessed. First, moderate physical activity and we're going to abbreviate that as MPA and that was 150 to 300 minutes per week, which is really recommended. Or second, vigorous physical activity for which it's really recommended that one performs 75 to 150 minutes per week. Now, Carolyn, as you know, some individuals accomplish both of these in their routine, some neither, some one or the other. And so it really remains unclear whether higher levels of long term vigorous or moderate are independently or perhaps jointly associated with lower mortality. Dr. Carolyn Lam: Oh, that's so interesting, Greg. Quick, quick, quick, tell us the results. Dr. Greg Hundley: Right Carolyn. So the nearly maximum association with lower mortality overall was achieved by performing approximately 150 to 300 minutes per week of long term leisure time vigorous physical activity or 300 to 600 minutes per week of long term leisure time moderate physical activity or an equivalent combination of both, so mixing those minutes. Also Carolyn, very interestingly, higher levels, suppose you go beyond those limits of either long term leisure time vigorous physical activity of more than 300 minutes per week or moderate physical activity of more than 600 minutes per week did not show clearly further lower all cause cardiovascular disease or non-cardiovascular disease mortality and nor did they show harm. So if you went above those thresholds, you really didn't experience greater harm. Dr. Carolyn Lam: Thanks, Greg. You know I'm going to be trying to apply that. That's so cool. All right. Well the next paper refers to the Cabana Trial, which I'll remind you is a trial in which catheter ablation did not significantly reduce the primary endpoint of death, disabling stroke, serious bleeding or cardiac arrest compared to drug therapy by intention to treat, but did improve quality of life and freedom from atrial fibrillation recurrence. In Cabana, the heart failure subgroup, ablation appeared to improve both survival and quality of life. The current paper led by Dr. Mark and colleagues from Duke Clinical Research Institute looked at the cost effectiveness of this ablation versus angio-rhythmic drug therapy in atrial fibrillation and which was a pre-specified Cabana secondary endpoint. Dr. Greg Hundley: Ah, Carolyn. So what did they find? Dr. Carolyn Lam: Well in this trial based economic evaluation, catheter ablation was estimated to cost $57,893 per QALY or Quality Adjusted Life Year gained compared to drug therapy in the overall cohort. And this was primarily driven by improvement in quality of life. It also cost $54,135 per QALY gained in the heart failure subgroup, driven by both gains in quality of life and survival. In summary, catheter ablation of atrial fibrillation was found to be economically attractive compared to drug therapy in the Cabana trial overall at present benchmarks of healthcare value in the US and based on projected incremental qualities, but not live years alone. Dr. Greg Hundley: Very nice Carolyn. Well, my next paper comes to us from the world of Preclinical Science and it's corresponding author is Dr. Swapnil Sonkusare from University of Virginia School of Medicine. So Carolyn, calcium signals in smooth muscle cells contribute to vascular resistance and control blood pressure. Now increased vascular resistance in hypertension has been attributed to impaired smooth muscle cell calcium signaling mechanisms. And in this regard, transient receptor potential vanilloid four or TRPV4 smooth muscle cell ion channels are crucial calcium entry pathways for smooth muscle cells. However, their role in blood pressure regulation has not been identified. Dr. Carolyn Lam: Wow. TRPV4 smooth muscle cells. Cool Greg. So what did they find? Dr. Greg Hundley: Right, Carolyn. So these authors provide the first evidence that TRPV4 smooth muscle cell channel activity elevates resting blood pressure in normal mice. A1AR stimulation activated TRPV4 smooth muscle cell channels through protein kinase calcium signaling, which contributed significantly to vasoconstriction and blood pressure elevation. Dr. Greg Hundley: Surprisingly, intraluminal pressure induced TRPV4 smooth muscle cell channel activity, opposed vasoconstriction through activation of calcium sensitive potassium channels indicating functionally opposite pools of TRPV4 smooth muscle cell channels. And so Carolyn, this team identified novel smooth muscle cell calcium signaling nano domains that regulate blood pressure and demonstrate impairment in hypertension. Dr. Carolyn Lam: Oh wow, Greg. Thank you so much for that. Well, let's cover the other articles in today's issue. There's a primer by Dr. Jaffe on High Sensitivity Cardiac Troponin and the 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR guidelines for the evaluation and diagnosis of acute chest pain. There's also Research [Letter] in there by Dr. Fordyce on the eligibility for non-invasive testing based on the 2021 American Heart Association and ACC guideline for the evaluation and diagnosis of chest pain, implications from the Promise trial. Dr. Greg Hundley: Great Carolyn. Well, I've also got an exchange of letters to the editor from Professors Benali and Professor Della Bella regarding a previously published article, “Does Timing of Ventricular Tachycardia Ablation Affect Prognosis in Patients with an Implantable Cardioverter Defibrillator, Results from the Multicenter Randomized Partita Trial.” And also there's a very nice Perspective piece from Dr. Udelson entitled “Glucose Insulin Potassium Therapy for Acute Myocardial Infarction, 50 years on and Time for a Relook.” Well, Carolyn, I can't wait to hear more of the discourse between you, the authors and editors on heart failure and preserved ejection fraction. Dr. Carolyn Lam: Yay. Here we go. I'm so excited about today's feature discussion. It's on my favorite topic, heart failure with preserved ejection fraction. Although thanks to one of the authors, Dr. Daniel Burkhoff of the editorial that accompanies it, I don't even know how to pronounce, it's Heart Failure question mark Ejection Fraction. I love it. How would you pronounce that? Dr. Daniel Burkhoff: Yeah, no, we debated how to pronounce it. HFQRef…a question mark? Dr. Carolyn Lam: HFQRef. Oh my goodness. What are we going to come up with next? Dr. Daniel Burkhoff: And we actually thought the editors would have a problem with that. Whenever we put something cute in the title, we always get knocked down. So we haven't yet got knocked down, so we'll see. Dr. Carolyn Lam: No, I'm not knocking you down. Dr. Daniel Burkhoff: But it just really emphasizes that we're in a very confusing time now as it comes to heart failure and ejection fraction, that we have to move on beyond ejection fraction. And although we have these strict buckets and upper and lower limits for each range, that maybe this is in a little bit of a way, doing us a disservice and doing the patients at disservice in terms of treatment. Dr. Carolyn Lam: That's really great. And everybody that was Dr. Daniel Burkhoff from the Cardiovascular Research Foundation in New York. He's the editorialist of today's feature paper. And I'm so excited that we have the corresponding author of today's feature paper as well, Dr. Philipp Lurz from Heart Center Leipzig in Germany. So first, I mean, or second, heartfelt congratulations on this beautiful paper, Philipp. If you could start with telling us all about what you did and what you looked at and what made Dr. Daniel Burkhoff call it now, Heart Failure, QREF? Dr. Philipp Lurz: Yeah. So thank you so much, first of all, obviously for having me for the kind introduction and your kind words about our work. The whole thing started with the observation that in recent drug trials, the response in HFpEF patients to drugs which were before proven to be quite successful in HFrEF actually showed a quite heterogeneous response in HFpEF patients. And that there were some patterns according to the range of ejection fractions. So it seemed that those HFpEF patients with the lower ejection fractions, they respond a little bit better to HFrEF medication than those with a higher ejection fraction. Dr. Philipp Lurz: And HFpEF studies, they included patients within and ejection fraction or 40 and above who normally would probably would consider HFpEF to start with 50 and above. But even in those truly HFpEF patients, so from 50 and anything above to 70, there was a suggestion that there might be differences. 50 to 60 might be something else and then 60 and above. And this is where we started to look into our cohort and to group them according to ejection fraction and see whether we can see some important and clinically meaningful differences in morphology, obviously in function, but then even also in terms of our biopsy results. Dr. Philipp Lurz: And that also implies that we did quite a deep phenotyping of our patients. So we use imaging, echo obviously. We use magnetic resonance imaging. We were able to acquire in a larger percentage of that cohort, by the way, it was 56 patients in total, we were able to get some left ventricular biopsies. And most importantly, when it comes to the functional properties of the left ventricle, we also acquired pressure volume loops. And that has the great advantage that we obviously we can look at low dependent parameters, but more important, also low independent in disease of both systolic and diastolic function. And that's pretty much what we did. Dr. Carolyn Lam: Oh my goodness. I mean, as an editor at Circulation, can I just first tell you that's what really, really stood out? It's the comprehensive, careful, in-depth characterization. It may be 56 patients, but MRI, echo, biopsies, exercise, PV loops. I mean, it was a lot, a lot that you did. Could you boil it down to what you found and maybe just to first clarify to the audience, how did you bend the ejection fraction? And then what you found? Dr. Philipp Lurz: We divided the cohort in two groups. One with an ejection fraction 50 to 60, and the other groups higher than 60% left ventricular ejection fraction. We ended up in lower group, 21 patients, in the higher group with 35 patients. And they were quite different. They had distinct features in terms of morphology, means that the lower injection fraction group, they had larger ventricles. That's probably what you would expect when you group them according to eject fractions. So not that surprising. Dr. Philipp Lurz: And at that point, and they had the same stroke volume. The low ejection fraction group, you could say that they had a certain degree of eccentric modeling, whereas those were the high ejection fraction group, that concentric modeling. When we then looked at the biopsies, the group with the low ejection fraction group, so 50 to 60, they had higher percentage of myocardial fibrosis at 15%. Dr. Philipp Lurz: And then on left ventricular biopsy, we saw that patients with a high ejection fraction group, they had less myocardial fibrosis, so more fibrosis in those with the lower ejection fraction group. And this is really interesting because when we then look at the real size of the pressure volume loop analysis, despite the fact that the high ejection fraction group had less fibrosis, they had the most stiff ventricles on pressure volume loop analysis. So that's already a very important point because it illustrates once again that we should not mistake fibrosis with stiffness, and also not the other way around. There are other parameters which can cause stiffness such as cellular stiffness, and it's not just the extracellular matrix. Dr. Philipp Lurz: So that's an important point. Those patients with high ejection fraction, they had the most stiff ventricles. They had the most relevant limitations in left ventricular filling, so the most marked diastolic dysfunction. We also looked at systolic parameters and there we found that they had a very high contractility. So this is the end systolic pressure volume relationship or also called elastics and that's a marker for contractility. So these ventricles with high ejection fraction, they can contract very well. They have high contractivity. But this is also a marker of systolic stiffness. So they stiff, both in terms of diastolic properties, but also systolic properties. And there, their most important limitation is the limitation in filling. Dr. Philipp Lurz: The other group, injection fraction 50 to 60, they do have some stiffness. Obviously we are talking about HFpEF. This is a disease of a diastolic dysfunction. So they have increased stiffness, but to a lesser extent. They can feel a little bit better, but what we see there is a reduction in contractility, so systolic properties. So you could argue that in some extent, that group 50 to 60, they behave a little bit more like HFrEF. Whereas those with high ejection fraction, they're completely different. Very stiff, both doing diastolically and sistolly. Dr. Carolyn Lam: Thank you so much. Now I really have to get the gurus insight into this. And of course by guru, I mean, Dr. Daniel Burkhoff. First, I'm going to take this opportunity to share a little private personal story that it's very hard for me to call Dr. Burkhoff, "Dan", although if you will allow me it's because I was a fellow when I first met Dr. Burkhoff. And one of my first papers was actually communicating with Dr. Burkhoff trying to draw these PV loops based on the noninvasive measurements that I was obtaining at the Mayo Clinic in the Olmsted County Cohort. And so this is just really making me smile. So Dan, if I may, what do you make of all this? And if you could give us what you think may be the clinical take home message. Dr. Daniel Burkhoff: Thank you so much, Carolyn. And also again, Philipp, congratulations on really a really important paper. I think as Carolyn was saying, one of the many things that impressed me was the multifaceted aspects of the thorough evaluation using multi modality characterization, which is in my mind, unprecedented, especially for this particular group of patients. And you summarized the main results very well. But to me, the thing that really struck me and that we really tried to emphasize in our editorial was the differential response to exercise, to hand grip exercise in this point. Dr. Daniel Burkhoff: As you already said, and I don't think this could be understated, that in the lower range, the 50 to 60, these patients were able to fill, the ventricle was able to fill more, the end diastolic pressure still went up significantly into an abnormal range, which is of course is one of the requirements for the diagnosis of HFpEF. But those patients, the end diastolic volume was able to increase and that helped them to increase their cardiac output. Dr. Daniel Burkhoff: In the higher EF group, the greater than 60, the end diastolic pressure went up, but the volume did not increase. So the end diastolic pressure volume relationship became higher elevated. And this of course, was reminiscent of what was identified in the early nineties by Dalane Kitzman. And really, he didn't make this distinction between the lower half and the higher half. And we had also in a paper that we did with David K and others, seen a similar finding a couple years ago. And I think this is really, to me, was the along with the apparently disparate findings on myocardial biopsies with fibrosis going the wrong way, if you will, as you already commented on. So this is at least for the higher EF group, is identifying what I would refer to as really true diastolic dysfunction. Dr. Daniel Burkhoff: That means that the patients can't fill, there really is some problem why the EDP can go up, but the volume does not increase. And this is obviously for future research, we have to understand what is the difference between these two groups. There are several speculations about why it might. For example, one thing that has been proposed in the literature is the pericardial restraints. If the heart is constrained in a tight pericardium, the volume is recruited from the venous system, which is another what I think is a very important part of this HFpEF phenotype, but the heart is already constrained. That would elevate both the CVP and the wedge pressure without concomitant increases in RV or LV volumes, and therefore limit the ability to increase the cardiac output. Dr. Daniel Burkhoff: Another alternative is delayed relaxation. That means a true abnormality of active relaxation. The tau if you will, but I believe in your study, if I remember correctly, the tau was not that abnormal and did not really change very much in either group. So it was harder to really pin it on an abnormality of active relaxation. So that was one really, I think, really important finding. Dr. Daniel Burkhoff: The second is now in the group 50 to 60 where they could fill, one of the limitations of the study that you pointed out was that there's no control group. So why this population, this HFpEF population, the EDP increased, but the EDV the end diastolic volume also increased, so what's different between those patients and normals? That we don't really have an answer for yet. So that would be one thing is to compliment these findings with results in a true control group that does not have HFpEF. Dr. Daniel Burkhoff: So we still have this mystery of why does EDP go up in this group? My perspective is not an abnormality of diastolly. It's not a diastolic dysfunction, even though it's a HFpEF. I've been trying to promote this idea for more than 20 years, that all HFpEF is not an abnormality of diastolic ventricular properties. There may be extra cardiac factors even beyond the pericardium in this group. So I think these results are just further telling us how complicated and individualized our approach to the pathophysiology of these patients should be. Dr. Daniel Burkhoff: And also just one final comment, making a strict cutoff at 60% or 57% as we saw from Valsartan Cuba trial, Valsartan study, is clearly also not going to do us justice. Let's say that we're dealing with anyway, patients with two different pathophysiologies. There's going to be a distribution of these different mechanisms and there's going to be an overlap of these distributions. So we need to start thinking about how we individualize and characterize the pathophysiology in individual patients. So maybe patients with EF of 55, certain patients with EF 55 will not respond to Sacubitril- Valsartan and maybe some patients with an EF of 62 will. So we need to go more deep into the clinical characterization. Dr. Daniel Burkhoff: And methods that you use in particular, the pressure volume loop, seem to separate, very nicely, these two different, at least two different subtypes. So I think it's very exciting, and I think people should really take notice of what you found and build on this as a foundation and understand that we need to go deeper on the clinical side to phenotype these patients. Dr. Carolyn Lam: Philip, what are your thoughts? Dr. Philipp Lurz: No, I think that the concept about stress and unstressed volume is extremely important and fascinating, but that's where it gets really complex because you could make the conclusion from our results that especially the high ejection fraction group, they are have a very high preload sensibility, which means that when we reduce pre-load too much in them, they drop the stroke volume very suddenly. So that's probably also the clinical question for the future. There are many patients, HFpEF patients in whom we should reduce stress volume and they can benefit from that. Dr. Philipp Lurz: But I also believe that there is a cord of patients, and those are probably more those with high ejection fraction. They actually, they could experience some harm if you reduce preload too much because of the severe filling restrictions, because of the inability to increase end diastolic volumes, especially as an adaptation to exercise. And I think if we find out ways to differentiate who will benefit from preload reduction and from decongestion and who actually might experience even harm from these interventions, then we are certainly one step further. Dr. Carolyn Lam: If I may, I just, I could go on forever, but I know that there's going to be this question that the audience is immediately thinking. Here we are going into the weeds, hemodynamics, we all love it. In fact, I think we're all kind of a little bit geeky about it, but then you've got, Emperor preserved, the Deliver Trial sort of being positive in heart failure with ejection fraction above 40. So, do we really need to understand the different hemodynamic? What do you think is happening that this sort of blanket benefit can occur? Dr. Philipp Lurz: I don't think that everyone will benefit. And I think that a better understanding of the underlying pathophysiology will help to even increase the rate of responders and dissect of those who will not respond or we need a different therapy. Obviously here we group patients according to ejection fraction. We just discussed that this is a very rough way to characterize patients. So the next step certainly would be to understand or to see distinct patterns in left ventricular functional behavior irrespective of ejection fraction. Because you might can skip ejection fraction at one day, but the conclusion is not, at least not in my opinion, that all heart failure is the same. Dr. Carolyn Lam: Nice. And Dan, what do you think? Dr. Daniel Burkhoff: Well, I think with STLT2 inhibitors, first of all, we're looking forward to actually seeing the results from Deliver what the details of it in terms of mortality versus hospitalizations and quality of life. But with regard to HSGL2 inhibitors, I don't think we know the mechanism. I mean, I've read about six papers that definitively talk about different mechanisms of action. I think we don't know. And even despite, let's say positive studies, there's still a significant residual risk that these patients have. So these are not the end of the story by any means. I think this is the beginning of the story and there's still going to be a lot to learn. Dr. Daniel Burkhoff: I think with SGLT2 inhibitors, I think it's difficult to identify who is or how do you define a responder on an individual patient basis? When we look at groups and you look at mortality and hospitalizations, yes, you can identify them. But that group does not overlap exactly with those who have an improvement in quality of life. So I think that we're just at the beginning, Dr. Daniel Burkhoff: I do think that a deeper phenotyping is going to be the way to go ultimately and I think we're going to need more therapies. Thanks again, Carolyn for inviting me to do the editorial and to participate in this. And I would really be remiss if I did not mention the extraordinary contributions for Mickey Brener and also Barry Borlaug who were equal contributors to this editorial and the evaluation of this paper. So I'm really indebted to both of them for this interpretations. And thank you again, Philipp, for just a wonderful paper. Dr. Carolyn Lam: Couldn't have said it better and I just want to thank you once again for providing that deeper phenotyping for opening the door. Many of us said it again and again, this is the beginning and we need more studies, frankly, in yours. I mean, I think Dr. Burkhoff wants you to send normal, healthy people for MRI biopsies, exercise, echo. I'm kidding, on PV loops, but it's true. We need that data. We need the same and the HFrEF and really just to understand the whole thing. I'm so excited about what this paper opens up. Dr. Carolyn Lam: I am thrilled to see your editorial, Dan. I'm sure it's going to be well received. Everyone who's listening to this, Pick up the paper, pick up the editorial. Thank you so much for joining us today. You've been listening to Circulation on the Run and from Greg and I, don't forget to tune in again next week, Dr. Greg Hundley: This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit hajournals.org.

Andrew Cleeland, CEO of Fogarty Innovation, welcomes back world-renowned cardiologist Dr. Marty Leon, a visionary leader who has shaped the worldwide practice of interventional medicine. Dr. Leon is professor of medicine at Columbia University Irving Medical Center (CUIMC), Director of Columbia Interventional Cardiovascular Care and of the Cardiac Catheterization Laboratories, founder and Chairman Emeritus of the Cardiovascular Research Foundation, and the driving force behind the Transcatheter Cardiovascular Therapeutics (TCT) conference. In this episode, Dr. Leon shares further insight into the later stages of his career and future aspirations.

There is virtually no aspect of the cardiovascular health ecosystem that hasn't been impacted by the work of Dr. Marty Leon, professor of medicine at Columbia University Irving Medical Center (CUIMC) and a legendary interventional cardiologist whose many roles and accomplishments have had an indelible effect on the practice of cardiology and the medtech industry. Dr. Leon's dedication is reflected by the many hats he wears, including Director of Columbia Interventional Cardiovascular Care and Director of the Cardiac Catheterization Laboratories. He is also the founder of the Cardiovascular Research Foundation and the Transcatheter Cardiovascular Therapeutics (TCT) conference. In this episode, Fogarty Innovation CEO Andrew Cleeland had the pleasure of chatting with Dr. Leon to learn more about the factors that shaped his life and career.

This week's episode features a panel discussion in regard to Covid-19. Please join authors Kathryn Larson, Christopher deFilippi, James de Lemos, and Biykem Bozkurt as they discuss their articles regarding temporary myocarditis and Covid-19 vaccination. Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts, I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, associate editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Greg Hundley: Carolyn, this week, oh my goodness. It's a forum, almost a triple or quadruple feature, and you know what we're going to be discussing? COVID-19 vaccinations and their relationship potentially to myocarditis. We're going to have our associate editors and our deputy editor involved, be really interesting. But before we get to that, how about we start in with the papers in the issue. Would you like to go first? Dr. Carolyn Lam: Absolutely. And my first paper is so interesting. It identified a novel underlying mechanism of graft arteriopathy, or otherwise known as coronary allograft vasculopathy, a devastating development of heart transplant in which arterial intimal thickening limits coronary blood flow and could lead to transplant failure. Dr. Greg Hundley: Oh wow, Carolyn. So, what did they find? Dr. Carolyn Lam: Well, this was Dr. Martin from Yale Cardiovascular Research Center and colleagues. What they did is they used both human coronary allograft vasculopathy and renal transplant samples as well as murine models, basically, and found that TET methylcytosine dioxygenase 2, or TET2, is a critical negative regulator of vascular smooth muscle cell apoptosis in graft arteriopathy and vascular injury. Enhancing smooth muscle TET2 activity with a high dose of ascorbic acid rescued donor vascular smooth muscle cells apoptosis and intimal thickening in murine transplant vasculopathy. Furthermore, TET2 expression and activity were repressed in arterial vascular smooth muscle cells in human and mouse graft arteriopathy compared to controls. Dr. Carolyn Lam: Interferon gamma signaling in vascular smooth muscle cells resulted in TET2 repression. Preventing donor vascular smooth muscle cell apoptosis with high dose ascorbic acid may therefore represent a safe and cost-effective therapeutic strategy for limiting graft arteriopathy in patients undergoing solid organ transplant. Neat, huh? Dr. Greg Hundley: You bet, Carolyn. Really an interesting article on limiting graft arteriopathy. Dr. Greg Hundley: Well, Carolyn, my next paper comes to us from Dr. Greg Stone and colleagues at the Cardiovascular Research Foundation. It involves the randomized COAPT trial. Remember that in the COAPT trial, there were 614 heart failure patients with 3+ or 4+ secondary mitral regurgitation and had trans-catheter mitral valve repair with the MitraClip, reduced mitral regurgitation, heart failure hospitalizations and mortality as well as improving quality of life compared with guideline directed medical therapy alone. So the authors here, Carolyn, sought to examine the prognostic relationship between mitral regurgitation reduction and outcomes in trans-catheter mitral valve repair versus guideline directed medical therapy alone. Dr. Carolyn Lam: Wow, okay. So, what did they find, Greg? Dr. Greg Hundley: Right, Carolyn. So, among patients with heart failure and severe, grade 3+ or 4+ secondary mitral regurgitation randomized to trans-catheter mitral valve repair with the MitraClip versus guideline directed medical therapy, the reduction of MR to 2+ was strongly associated with subsequent two year freedom from death and heart failure hospitalization and improved quality of life regardless of whether this reduction to 2+ MR was achieved by trans-catheter clip or guideline directed medical therapy alone. And the improvement in long term prognosis was similar after this mitral regurgitation reduction to grade 2+ compared with grade 0 or 1+ in both arms, although the mitral regurgitation reduction was a little more durable over time after the trans-catheter mitral clip. Dr. Greg Hundley: So Carolyn, the take-home message is that substantial benefits are realized even if mitral regurgitation is reduced to only 2+. Dr. Carolyn Lam: Nice, Greg. Thanks. Dr. Carolyn Lam: Now, this next paper, oh, close to my heart. We know that individuals of South Asian ancestry actually represent 23% of the global population, corresponding to 1.8 billion people, and that they have a substantially higher risk of atherosclerotic cardiovascular disease compared with most other ethnicities. However, what is the magnitude of that enhanced risk, the extent to which it is captured by existing risk estimators, and what are its potential mechanisms? Dr. Carolyn Lam: This was studied in this beautiful paper. Dr. Khera from Massachusetts General Hospital and colleagues used data from the large UK Biobank prospective cohort study to investigate the relationship between South Asian ancestry and incident atherosclerotic cardiovascular disease within the context of contemporary medical care. Their findings confirmed an approximate doubling of atherosclerotic cardiovascular disease risk among South Asian compared with European individuals that was not captured by the pooled cohort equations. The higher risk of atherosclerotic cardiovascular disease persisted despite adjustment for a broad range of potential clinical, anthropometric, and lifestyle mediators. Hypertension, diabetes, and central adiposity explain a greater proportion of risk of atherosclerotic cardiovascular disease in South Asian compared with European individuals. Dr. Greg Hundley: Wow, Carolyn. So, a lot of data here. How do we take all this and put it together clinically? Dr. Carolyn Lam: Well, the results confirm and extend the current guidelines that consider South Asian ancestry a risk-enhancing factor in assessing future risk for atherosclerotic cardiovascular disease. Residual risks that persisted after accounting for a range of potential mediators may relate to differences in social determinants of health, unmeasured risk factors and genetics and so on, that this warrants further investigation. Whether a targeted intervention can attenuate the outsized impact of diabetes or central adiposity among South Asian individuals also warrants further attention. Dr. Carolyn Lam: This is accompanied by a beautiful editorial entitled The South Asian Enigma: Solving a Puzzle of Global Importance, love that, from Drs. Kandula from Northwestern University Medical Center and Kanaya from University of California San Francisco. Dr. Greg Hundley: Very nice, Carolyn. I just want you to know, after being quizzed last week on phospholamban, I went and did a little bit of studying, okay? So I get to bring to you, Carolyn, this week, a paper on phospholamban. But I'm going to spare you from the quiz. Dr. Greg Hundley: All right. Dr. Carolyn Lam: Yay! Dr. Greg Hundley: This comes to us from Professor Fadi Akar from Yale University. Carolyn, arginine 14 deletion is the calcium regulatory protein phospholamban, so hPLN R14 deletion. It has been identified as a disease-causing mutation in patients with an inherited cardiomyopathy, and mechanisms underlying the early arrhythmogenic phenotype that predisposes carriers of this mutation to sudden death with no apparent structural remodeling really remain unclear. Dr. Carolyn Lam: Interesting, Greg. So, what did they find? Dr. Greg Hundley: Right, Carolyn. Adverse electrophysiological remodeling was evident in the absence of significant structural hemodynamic changes, and the R14 deletion hearts exhibited increased arrhythmia susceptibility compared to their wild-type counterparts. Underlying this susceptibility was preferential right ventricular action potential prolongation that was unresponsive to beta-adrenergic stimulation. A steep repolarization gradient at the LV/RV interface provided the substrate for inter-ventricular activation delays and ultimately local conduction block during rapid pacing. This was followed by the initiation of macroreentrant circuits supporting the onset of ventricular tachycardia. And then once sustained, these circuits evolved into high frequency rotors, which in their majority were pinned to the right ventricle. Importantly, these rotors exhibited unique spatio-temporal dynamics that promoted their increased stability in the R14 deletion compared to the wild-type hearts. Dr. Greg Hundley: So Carolyn, in summary, this research found the crucial role of primary electrical remodeling caused by the hPLN R14 deletion mutation. These inherently arrhythmogenic features form the substrate for adrenergic-mediated VT at early stages of the PLN R14 deletion induced a cardiomyopathy. Dr. Carolyn Lam: Oh, and ties up very nicely about how we mentioned that this dilated cardiomyopathy is associated with lots of ventricular arrhythmias that we discussed last week. Really cool. Dr. Carolyn Lam: Well, let's do a little tour around what else there is in today's issue. Tracy Hampton presents from the literature discussing how excessive exercise may damage mitochondria and impair glucose control in a publication from Cell Metabolism. Data on an oral antisense oligonucleotide for PCSK9 inhibition was published in Science Translational Medicine. Dr. Carolyn Lam: And there's a paper on structuring clinical text with AI. How very interesting, published in Patterns. There's an On My Mind paper by Dr. Berger on summoning strength to question the placebo in reducing. Dr. Greg Hundley: Right, Carolyn. Also in the mail bag, there is a reply to the Quintao and Cazita from Professor Brunham entitled High-Density Lipoprotein Cholesteryl Ester Transfer Protein and Sepsis. And then finally, from Dr. Goldstein, an ECG challenge. Does this ischemia pattern look right? Dr. Greg Hundley: Well, Carolyn, this is going to be a really interesting feature forum discussion today on COVID-19 vaccinations and myocarditis. How about we get on to that discussion? Dr. Carolyn Lam: Yep. A really important issue now. Yup, let's go. Dr. Greg Hundley: Welcome, listeners. We have a very exciting, really series, of feature discussions. We're going to call it a forum, and focusing on COVID-19 vaccine associated myocarditis. We really have four manuscripts to discuss today. We have Dr. Kathryn Larson from the Mayo Clinic in Rochester. We have another author, Dr. Chris deFilippi from Inova Health, really in the Washington DC metro area. We have our executive editor, Dr. James deLemos from UT Southwestern in Dallas, Texas. And then also one of our senior associate editors, Dr. Biykem Bozkurt from Baylor College of Medicine in Houston, Texas. Welcome to everyone. Dr. Greg Hundley: Well, first, listeners, we're going to start with Dr. Larson. So, Kathryn, can you tell us a little bit about the background and the hypothesis that you were testing in your research project, and then a little bit about your study design and what were the results of your study? Dr. Kathryn Larson: Absolutely. Well, first off, thank you so much for having me, Greg. It's a pleasure to be here and in such good company. My study really grew out of a clinical interest in a number of patients that had presented to our institution and other institutions that we had been in discussion with of really young male patients with no significant past medical history who were coming in two to three days after receiving their COVID vaccines, most often the second dose, and presenting with laboratory and clinical findings consistent with myocarditis. I think in a lot of arteriosity and what the course of their illness may be and what the best course of treatment may be, that really drove our hypothesis to try and describe other cases that were coming up and that we had heard about from a lot of our colleagues around the country and around the world. Dr. Kathryn Larson: Our paper really grew out of a case series of eight patients, and they're from the United States and from Italy, and they're of eight patients who were diagnosed with laboratory and clinical and imaging findings consistent with myocarditis after receiving their COVID-19 vaccines. Our patients had received either the Pfizer BioNTech or the Moderna vaccines, the mRNA vaccines. Really, only two of our patients had previously been infected with COVID at all, and so most of these patients were coming in with really no relevant medical history. They were really young in age, between 21 and 56 years old, and basically all patients except for one developed their symptoms after receiving the second dose of the vaccine. Dr. Kathryn Larson: The timeline was generally about two to three days after that dose and was often accompanied by other symptoms which we have seen and heard about things like myalgias, subjective fevers, chills, and kind of a general malaise. They presented really with very typical features of myocarditis, chest pain, one of the patients had a more pleuritic type of chest pain, and had ECG changes, troponin elevations, elevated inflammatory markers, and most importantly cardiac MRI findings that were significant and really diagnostic of myocarditis. Dr. Kathryn Larson: There was a good amount of investigation into other potential causes and none other identified in any of those eight patients. All thankfully had a relatively unremarkable course clinically and all are currently doing very well. There was mild reductions in LV function, no clinically significant heart failure, and at last known contact, those patients really had recovery of LV function and are essentially back to baseline. Dr. Greg Hundley: Excellent. Well, listeners, we're going to move to another part of the country, and again, Dr. Chris deFilippi is in the Washington metro area. Chris, you also have a case series. Can you describe for us what you were looking at with your study, and then what were your study results? Dr. Chris deFilippi: Greg, first, thank you for having me here today. As a regular listener to Circulation on the Run, it's really a privilege to actually be able to participate and contribute to it. First, I would have to say was a little bit of serendipity. We recognized one case out of the ordinary with respect to suspected myocarditis in early March, and given our location around Washington DC, some of our faculty were former active military and serve in the reserves and one returned and said, "The military is beginning to find a small series of cases." Dr. Chris deFilippi: We've worked hard within our academically oriented independent health system to develop a research clinical trials network, and we called upon our cardiologists and cases started coming forward actually fairly rapidly, drawing upon five hospitals in our network. Combining our efforts with UT Southwestern, we identified seven individuals. They were all men or young adults in their 20s and 30s. Six out of seven had received the mRNA vaccines. Most of them had developed symptoms between three to seven days after their second vaccination. Dr. Chris deFilippi: Very similar to Kathryn's presentation, we did an extensive evaluation, of course including advanced imaging with MRI using the Lake Louise criteria, but also did a lot of serologic measurements. I think it was remarkable that troponin values using still a conventional assay ranged from mild elevations, 0.34 to as high as 44 milligrams per milliliter. Dr. Chris deFilippi: All patients fortunately had resolution of symptoms within several days and returned back to normal life and then all return follow-ups seemed to remain symptom-free. Again, we looked for multiple other etiologies including autoimmune disease, other respiratory infections, and these were all effectively negative. Dr. Greg Hundley: Very nice. Well now, listeners, we're going to head south, down to Dallas, Texas and bring in Dr. James deLemos. James, you also have a case report and did some extensive study, I believe, in your patient in terms of investigating perhaps mechanisms. Could you share with us your study and some of your findings? Dr. James deLemos: Yeah. Thanks, Greg. Ours was like Kathryn and Chris's experience, purely serendipitous. I was on service in late January at our university hospital and we had a case that came in three days after receiving the Moderna vaccine with what appeared to be clearly myocarditis in temporal association with the vaccine. At that time, we reported it to the CDC, but there was really not much, if anything, and so what we decided to do was pull together a translational team. We brought together clinical pathologists, immunologists, infectious disease experts, and a panel of folks to think about how we might get at a potential mechanism, obviously in a highly exploratory fashion because this was one case and at this point we really didn't know whether this was a true causal association or just circumstance. Dr. James deLemos: What we did was really a broad exploratory analysis, comparing our index case with a number of vaccinated controls, COVID infected controls, and normal controls. We did autoantibody panels, cytokine panels. We looked at flow cytometry for cell fractions, and really tried to see if there was a signature for our case that distinguished it from these other control groups. Dr. James deLemos: I think one important thing we didn't see was an exuberant or over exuberant response in terms of the spike antibody. That was also not seen in several other cases from Chris and Kathryn. The antibody response seemed to be in the normal range of what would be expected after the vaccine. We also didn't see broad spread inflammation in our case compared to controls. There were several cytokines that were upregulated, some of which have been reported in myocarditis, and there were some natural killer cell subsets that would seem to be upregulated, and then several autoantibodies as well that have been reported in myocarditis. But interestingly, none of the poor prognosis autoantibodies that had been reported, which may in part, we think, explain why these cases seem to be doing quite well. Dr. James deLemos: I'd emphasize it's one case, so we recognize this is purely exploratory and hopefully will set the stage for other people as they try to investigate this in more depth. Dr. Greg Hundley: Thank you, James. Well, Biykem, you've been spending a large segment of time, the last year, really year and a half, trying to put together for us at the American Heart Association what may be operative in these patients receiving these vaccines, and also really studying COVID-19. It sounds like what we're hearing amongst all three of these, young men, really a myocarditis that develops after the second vaccine. We have typically elevated troponins, there's MRI findings. You've put together a review. Maybe you could start to share with us what have you learned over this past year and a half? Dr. Biykem Bozkurt: Thank you, Greg. As my colleagues have alluded to, the characterization of the presentation is pretty concordant. What I did in the review was to review all the case reports and case series published to date, which summed up to 61 cases. Additionally, I looked at what has been reported by the Vaccine Adverse Event Reporting System by the CDC and their internal analyses, and also looked at the reports that came from Israel as well as the US military, which is a large cohort and population base reporting. Dr. Biykem Bozkurt: The messages for the clinicians, number one, the presentation in most of these reports have been pretty unified in the sense that most patients presented day two or day three after the second dose of mRNA vaccination. Secondly, most if not all had cardiac troponin elevation along with chest pain on presentation. The majority of the patients, more than 90, 95 in the case series, had EKG abnormality, usually with ST elevation. When we're to examine the echo findings, about two thirds or sometimes in the case series about 40% of abnormalities and only a small percentage had LV systolic dysfunction with EF less than 50. Dr. Biykem Bozkurt: When done as was the case in all the case series and case reports, cardiac MRI was always abnormal. They were very self-limited. Important concepts are, these were very self-limited cases. All of them recovered and were discharged and had resolution of their symptoms, biomarker findings as well as imaging findings. Dr. Biykem Bozkurt: Now, let's look at the benefits versus risk concept that was examined at the CDC level. The current reporting in the VAERS system, the Vaccine Adverse Event Reporting System, is about 12.6 cases per million doses of vaccination. This is after 300 million doses being given in the US and about 170 million individuals being vaccinated in the US. Of those, when compared to what we have been expecting in the population, there appears to be a temporal association that the CDC has confirmed. If we were to look at the risk versus benefits ratios, it's very clear that COVID-19 is a deadly disease. It results in mortality even amongst the younger population, somewhere at the order of 0.1 to 1% per 100,000 people being infected. So for 12 to 39 years old, where the myocarditis risk is felt to be higher, still we need to keep in mind, that risk is very low. 12 per million doses, compared to about 0.1 to 1 death for about 100,000 infections. Dr. Biykem Bozkurt: And of course, if we were to add the number of hospitalizations, ICU stays, cardiac involvement, which we know is seen in about 12 to 20% of hospitalized patients by cardiac troponin elevation, as well as multisystem inflammatory syndrome that is seen in young populations, the benefits significantly outweigh the risks. In terms of mechanisms which James has alluded to, the things that are coming as potential signals or hypothesized mechanisms include the following. There could be molecular mimicry between the spike protein and the self-antigens. Currently, that experimental data, antibodies against spike protein have been reported to cross react with human proteins including alpha myogen. Other mechanisms could be vaccine and it making a response triggering a pre-existing dysregulated immunopathological pathway in predisposed patients. But mind you, we don't right now have a pattern of who's predisposed to myocarditis. It doesn't look like comorbidities as we have seen with COVID-19 infection. Dr. Biykem Bozkurt: And in James' case, there was no predisposition to cardiomyopathy identified by a gene variant that are known to be associated, so those were negative in the case reports that James had mentioned. There was increased frequency of autoantibodies in that case report that James had published. Again, this may be in reaction to the inflammation or injury rather than being the cause. It may be the outcome, but still it raises a concern whether autoantibody formation is one of the mechanisms. Dr. Biykem Bozkurt: Male predisposition is a known risk for myocarditis. We've known this even before the vaccine related myocarditis cases. In the experimental as well as population based studies in the past, young males have a higher predisposition than females or older age, and it's thought to be due to the differences related to sex hormones, especially testosterone, being pro-inflammatory. But of course, in the passive vaccine adverse event reporting, we also do know that the chest pain presentation did not appear to be as different among males compared to females and the imaging and studies were done in less frequency in females, so there may be also a bias toward work-up in females which needs to be further examined. Dr. Biykem Bozkurt: The most important message we'd like to put out there is the benefits highly outweigh the risks, but there needs to be recognition that there is such a risk for clinicians, and definitely do an appropriate work-up for patients presenting with chest pain to the emergency room or to the clinical setting for an appropriate work-up to be carried out including EKG, cardiac troponin in all patients, followed by imaging, such as cardiac MRI and/or other imaging as necessary depending on the symptomatology, the age, as well as the findings on the troponin and EKG. And cardiology moment is essential for those ones who are diagnosed with myocarditis. The treatment strategies in the case reports range all the way from non-steroidal colchicine to IV steroids to intravenous immunoglobulin. Probably the way to approach these cases is if it's very self-limited with resolution of symptoms and biomarkers within two or three days, they may not need to resort to very intensive therapy, but if the case is with unrelenting symptoms, persistent biomarker abnormality, an imaging finding higher level of intense geo-treatment with intravenous steroids or IV immunoglobulin may be considered. Dr. Biykem Bozkurt: So far in the published reports, there have not been any bad outcomes such as death and/or requirement for mechanical circulatory support, but again, further research is needed. Dr. Greg Hundley: Very nice, Biykem. Well, listeners, we're going to go back through our authors and just really quickly, Kathryn, Chris, James, Biykem, what study, maybe in 15 seconds, do you think might need to be performed next in this sphere of research? And then second, what's the one point that you think we ought to emphasize as we close out going forward? So, both questions for each author. Kathryn, we'll start with you. Dr. Kathryn Larson: Okay, cool. I think I'll bring a little bit of an imaging bias as that's my personal interest. I'd really like to see a lot of the data that's already out there from these patients both at their baseline studies, and I'd really like to see their follow-up studies in terms of what happens to things like LV function and in terms of their MRI findings. I think that could be really helpful given the amount of weight that imaging has in the diagnosis of these patients. Dr. Kathryn Larson: I think the biggest take-away for me in a lot of these discussions that we were having is, these are very rare issues and incidents when patients are presenting with these, and I think the vast majority of the information we have at hand is that these are self limited, there's good recovery of any decline in LV function, and that I think overall the clinical course is favorable. Dr. Greg Hundley: Very nice. Chris? Dr. Chris deFilippi: First, I shouldn't be promoting my colleague's work, but I've got to say that Biykem's review was terrific. I know I did a lot of background reading in this case presentation. I've gone through that review a couple times and it's clearly, I think, helped my thinking on this topic. As Biykem mentions in that review, the recording of myocarditis can have a number of biases either under or over reporting, basically what's available in the public and what sort of people are thinking about. I think looking at it from a population health standpoint, the risk benefits are so favorable for the benefits of vaccination. We knew that even a month ago, we know that even more today. But I think it would be great to get an understanding, recognizing that there may be cases of unrecognized myocarditis, myocardial fibrosis, at a population level in what we would assume would generally be very healthy, young adult males, do we see more cardiac related hospitalizations over time? Do we see more sudden death? I think we should just affirm that, hopefully we can affirm that isn't the case and keep moving forward. Dr. Chris deFilippi: That being said, I'm still really a big advocate for vaccination and the benefits of vaccination combined with these very small risks. Dr. Greg Hundley: Very nice. James? Dr. James deLemos: I'd say really two avenues for research. I'd echo Kathryn's point that we need longer term follow-up data for patients that have this syndrome. To do that we're going to have to collaborate, because each of us individually see very few cases, because fortunately this is rare, and we're going to need registries that look at longer term follow-up of patients with vaccine associated myocarditis. And then really getting to Chris' point on the front end, I think that's what's needed are prospective studies measuring high sensitivity troponin and cardiac MRI in younger individuals who get vaccinated, so we study them not once they get the disease, but trying to determine whether there might be even less severe versions of myocardial injury that are occurring after the vaccine and try to understand why that's the case, because mRNA vaccines are here to stay. They're remarkable advances. And let's understand what this apparently self limited myocarditis is all about. Dr. James deLemos: The take-home message I'd echo is that this is important and all of us even had angst about recording and talking about this, because we don't want this ever to be misconstrued to suggest that these vaccines, which are absolutely remarkable, don't have a favorable risk benefit, even for our cardiac patients. These data in no way affect the safety and efficacy of the vaccine, even in people with underlying cardiac disease, who are some of the ones that have the greatest priority to get vaccinated. Dr. Greg Hundley: And finally, Biykem. Dr. Biykem Bozkurt: I think I echo all my colleagues' sentiments in the necessity for prospective and imaging and biomarker. The way to do that, as James alluded to, is we should right now develop a consortium for a registry, and we should have a bioregistry. I would urge us to not solely consider it for vaccine related entity, but also COVID-19. So I think we need to straddle the whole concept of COVID-19 itself, the infection plus the vaccinated individuals and follow them in a prospective manner with the known biomarkers, the cardiac biomarkers as well as imaging, but also the thing that is lacking right now is to characterize them with a specific immune cell populations as to what is rising, what kind of response we've seen, with the changes that we're seeing in males and others, and capture further mechanistics, perhaps signaling. Quite a few of this phenotyping is needed in these individuals as well as perhaps a genotyping characterization and maybe a tissue characterization. Dr. Biykem Bozkurt: I think the consortium will need to entail pathologies as well as immunopathology along with biomarkers and imaging. And of course, prospectively following these individuals. As was done in certain other vaccines in the past may give us a totally different signal and prevalence. Dr. Biykem Bozkurt: Take-home message, I fully agree. Being able to get a message of the risk is low compared to benefit. While we're calling for, the necessity for further research is a delicate balance of what the scientists have to straddle. Yes, the vaccine is very safe. It's been shown in numerous, several randomized clinical trials. Current data actually validates that because it's a few cases in millions of doses of the safest vaccine. But for those very few cases, for those very few cases we need to be on the alert and treat them appropriately and not miss those diagnoses. Dr. Biykem Bozkurt: One other message I'm going to share is the rapidly evolving conceptualization of myocarditis. The lymphocytic myocarditis concept that historically was the gold standard characterization of myocarditis with other viruses is, I think, rapidly changing now with the recognition of what we saw with COVID-19 itself, as well as now with the vaccine. It does not seem to be the classical characterization of myocarditis, so again, understanding of myocardial injury, cardiomyocyte injury is now a continuum beyond what we used to call the path to MI and injury, now straddling all the way to a concept of injury that is much different than the lymphocytic myocarditis we've seen with other viruses, which we need to embrace. Dr. Greg Hundley: Very nice. Well, listeners, we want to thank Dr. Kathryn Lawson, Dr. Chris deFilippi, Dr. James deLemos, Dr. Biykem Bozkurt, for this wonderful forum discussion on COVID-19 vaccine associated myocarditis. Dr. Greg Hundley: Well, thank you so much and on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week On the Run. Dr. Greg Hundley: This program is copyright of the American Heart Association 2021. Dr. Greg Hundley: The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit AHAJournals.org.  

Dr. David Cohen is the Director of Clinical and Outcomes Research at the Cardiovascular Research Foundation in New York, NY. He is also a Professor of Medicine at Columbia University School of Medicine. In addition, he is a practicing interventional and structural cardiologist at St. Francis Hospital in Roslyn, NY as well as their Director of Academic Affairs. Dr. Cohen completed his MD at Harvard Medical School along with a Masters degree in Health Policy at the Harvard School of Public Health. From there, he completed his training in internal medicine at Brigham and Women's Hospital in Boston. Following that, he did his cardiology and interventional cardiology training at Beth Israel Hospital in Boston. In this podcast, Dr. Cohen talks about what it's like to be an interventional and structural cardiologist in addition to being a Director of Academic Affairs and Professor, his unique hobby that helps him relax, and his reasons for getting into cardiology. Dr. Cohen also describes in simple words what occurs during a minimally invasive heart catheterization and a coronary angioplasty procedure. White Coat Story is a podcast series for school students to gain first-person insights into the practice of medicine, and what it takes to get there.

This week's podcast features author Nicholas Mills and Guest Editor Allan Jaffe as they discuss the article "High-Sensitivity Cardiac Troponin on Presentation to Rule Out Myocardial Infarction: A Stepped-Wedge Cluster Randomized Controlled Trial." (https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.052380) Dr. Carolyn Lam: Welcome to Circulation On The Run, your weekly podcast summary, and backstage pass to the journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke-National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, Associate Editor/Director of the Pauley Heart Center and VCU Health in Richmond, Virginia. Well, Carolyn, this week's feature, we're going to examine cardiac troponin, high-sensitive cardiac troponin, and its association with myocardial infarction. But first, before we get to that, how about we grab a cup of coffee and start in and review some of the other articles in the issue? Would you like to go first? Dr. Carolyn Lam: I would love that. The first paper brings up the problem of stroke, remaining a devastating complication of transcatheter aortic valve replacement or TAVR. Now, this stroke risk has persisted despite refinements and the technique and increased operator experience, while cerebral embolic protection devices have been developed to mitigate this risk data regarding their impact on stroke and other outcomes after TAVR are limited. Dr. Carolyn Lam: Dr. David Cohen from Cardiovascular Research Foundation in New York and colleagues performed an observational study using data from the STS-ACC TVT registry, including more than 123,000 patients from almost 600 sites who underwent elective or urgent transfemoral TAVR between January 2018 and December 2019. Dr. Greg Hundley: Wow, Carolyn, this sounds like a really good use of the registry. What were the results? Dr. Carolyn Lam: Indeed, in this nationally representative observational study, the authors did not find an association between embolic protection device use for TAVR and in-hospital stroke in their primary instrumental variable analysis. And that's a technique designed to support causal inference from observational data with site-level preference for embolic protection device use within the same quarter of the procedure as the instrument. Dr. Carolyn Lam: However, they found a modestly lower risk of in-hospital stroke in their secondary propensity weighted analysis. These findings provide a strong basis for large-scale randomized control trials to really test whether embolic protection devices provide meaningful clinical benefit for patients undergoing TAVR. And this is discussed in a nice accompanying editorial by Dr. Tam and with Wijeysundera from University of Toronto. Dr. Greg Hundley: Very nice Carolyn. Well, my first paper comes to us from Professor Hua Zhang from Shanghai Children's Medical Center. Cyanotic congenital heart disease is a complex pathophysiological condition involving systemic chronic hypoxia and some cyanotic congenital heart disease patients are chronically hypoxic throughout their lives which heightens their risk of heart failure as they age. Dr. Greg Hundley: Hypoxia activates cellular metabolic adaptation to balance energy demands by accumulating hypoxia-inducible factor 1-Alpha. And Carolyn, this study aims to determine the effect of chronic hypoxia on cardiac metabolism and function in cyanotic congenital heart disease patients and its association with age. The authors investigated the role of hypoxia-inducible factor 1-Alpha in this process, and the potential therapeutic targets for this were explored. Dr. Carolyn Lam: What did they find Greg? Dr. Greg Hundley: In cyanotic congenital heart disease patients maladaptation of cardiac metabolism occurred during puberty, along with impaired cardiac function. In cardiomyocytes, specific HIF1-Alpha knockout mice, chronic hypoxia failed to initiate the switch of myocardial substrates from fatty acids to glucose, thereby inhibiting ATP production and impairing cardiac function. Increased insulin resistance during puberty suppressed myocardial HIF1-Alpha and was responsible for cardiac metabolic maladaptation in animals exposed to chronic hypoxia. Dr. Greg Hundley: Pioglitazone significantly reduced myocardial insulin resistance, restored glucose metabolism, and improved cardiac function in pubertal chronic hypoxia animals. And so, Carolyn, perhaps future studies could test whether pioglitazone administration during puberty might improve cardiac function in cyanotic congenital heart disease patients. And this article is nicely accompanied by an editorial from Professor Ghofrani. Dr. Carolyn Lam: That's really interesting. For the next paper we're going from cyanotic congenital heart disease to plain old hypertension asking the question, What is the association of blood pressure classification using the 2017 ACC/AHA blood pressure guideline with risk of heart failure and atrial fibrillation? Well, this question was addressed by Dr. Kaneko and colleagues from University of Tokyo who performed analysis using a nationwide health claims database collected in the JMDC claims database between 2005 and 2018. Now note, this was more than 2 million patients followed for a mean of more than a thousand days in whom more than 28,000 incident heart failure, and more than 7,700 incident atrial fibrillation events occurred. Dr. Greg Hundley: Carolyn, this is a really large cohort a lot of events. What did they find here? Dr. Carolyn Lam: Among adults not taking anti-hypertensive medications and with no prevalent history of cardiovascular disease, stage one and stage two hypertension, according to the 2017 ACC/AHA blood pressure guidelines was associated with a higher incidence of heart failure and atrial fibrillation. The population attributable fractions for heart failure associated with stage 1 and stage 2 hypertension were 23.2% and 51.2% respectively. The population attributable fractions for atrial fibrillation associated with stage 1 and 2 hypertension were 17.4% and 34.3% respectively. The categorization based on 2017, ATC/AHA blood pressure guidelines may improve risk stratification for identifying adults at high risk for heart failure and atrial fibrillation. Dr. Greg Hundley: Wow Carolyn. Really useful data and something I love about our journal, a transition from a large cohort study on hypertension, and now we're going to delve into the world of preclinical science and talk about myocardial hypertrophy. Carolyn, exercise can induce physiological myocardial hypertrophy and former athletes can live five to six years longer than non-athletic control suggesting a benefit after regression of physiological myocardial hypertrophy. Dr. Greg Hundley: Accordingly, these authors led by Professor Yulin Liao from Nanfang Hospital and Southern Medical University hypothesized that anti-hypertrophic memory exists after physiologic myocardial hypertrophy has regressed increasing myocardial resistance to subsequent pathological hypertrophic stress. In this study, C57BL, six mice were submitted to 21 days of swimming training to develop physiological myocardial hypertrophy. Then after termination of the swimming events and exercise, the physiological myocardial hypertrophy regressed within a week. And these physiological myocardial hypertrophy regression mice termed the exercise preconditioning group or HP, and then sedentary mice as a control group underwent transverse aortic constriction, or a sham operation and were observed for four weeks. Dr. Greg Hundley: Finally, in these two groups, cardiac remodeling and function were evaluated using echocardiography invasive left ventricular hemodynamic measurements and histological analysis. Dr. Carolyn Lam: Wow. Exercise induced and I hypertrophic memory in the heart. That is so cool. Greg, could you summarize what they found? Dr. Greg Hundley: Yeah. And how about that exercise stimulus? The mice were swimming. Carolyn, these authors found that exercise-induced physiological myocardial hypertrophy can produce cardioprotective effect. And this cardioprotective effect continues to exist after the physiological myocardial hypertrophy subsides. And it's termed a phenomenon exercise hypertrophy preconditioning. Dr. Greg Hundley: Now, mechanistically, the investigators found that exercise hypertrophy preconditioning up regulates the expression of the long noncoding RNA Mhrt779 by increasing the three methylation of histone 3 at the A4 promoter of Mhrt779. Dr. Greg Hundley: Carolyn, also cardiac overexpression are knocked down of Mhrt779 respectively enhanced or weakened the anti hypertrophy effect of exercise hypertrophy preconditioning. The clinical implications of this research are that these results will likely stimulate further research into the mechanisms of exercise hypertrophy preconditioning, and Mhrt779 may be a potential therapeutic target for myocardial heart hypertrophy and heart failure in clinical practice. Dr. Carolyn Lam: Wow. Thanks so much, Greg. That was an incredible summary. Dr. Carolyn Lam: Let me tell you what else is in today's issue. There's an exchange of letters amongst doctors Mehmood Donkor, and Westermann regarding the article “Left Ventricular Unloading is Associated with Lower Mortality in Cardiogenic Shock Patients Treated with Venal Arterial Extracorporeal Membrane Oxygenation.” There's an ECG Challenge by Dr. Bhasin regarding “A Young Woman with Palpitations. Is It a Poison or Is It a Reality?” Dr. Carolyn Lam: In Cardiology News by Tracy Hampton, she describes new research, revealing mechanisms behind exercise-induced heart damage, new details behind muscle injury repair, and new insights on plasma membrane rupture during cell death. Very interesting. A new section there. There's a Perspective piece by Dr. Passman on “'Pill in the Pocket?' Anticoagulation for Atrial Fibrillation. Is That Fiction, Fact, or Foolish?” Dr. Greg Hundley: Great, Carolyn. Well also in the mailbag, there's a Frontiers and medicine piece from Professor Rohatgi entitled “HDL in the 21st Century: A Multifunctional Roadmap for Future HDL Research.” And then finally, Carolyn, a Research Letter from Professor Felker, entitled Probabilistic Re-adjudication of Heart Failure Hospitalization: Events in the Paragon-HF Study.” Well, Carolyn, what a great group of articles summarized. How about now we proceed to that feature discussion? Dr. Carolyn Lam: Let's go Greg. Dr. Greg Hundley: Well, listeners. We are now to our featured discussion today and we have with us one of our associate editors who has submitted a paper, Dr. Nick Mills from Edinburgh, Scotland. And then we have a guest editor. Sometimes he's been a feature author, but now he's serving as a guest editor, Dr. Alan Jaffe from Rochester, Minnesota. Welcome gentlemen. Dr. Greg Hundley: Well, Nick, could you start us off first and describe for us the hypothesis that you wanted to test, and then maybe also provide a little bit of context or background around the study that you and your team have just performed. Dr. Nicholas Mills: Thanks, Greg. I've been working for about a decade trying to understand how we can get the value from high-sensitivity cardiac troponin in our clinical practice. We've tried a number of different approaches to implement them for the benefit of patient care that I'm particularly proud of this trial. What we'd recognized that I think with the rollout of these assays across Europe and more recently in America is that they're excellent tests, but they do generate some diagnostic uncertainty in clinical practice. Dr. Nicholas Mills: But as we've got used to using them, we've learned that actually their major strength is that the confidence that they bring in ruling out myocardial infarction rather than ruling it in. And they allow us to make really early decisions often with a single test at the point of arrival, where we can say with absolute confidence that a patient does not have acute coronary syndrome and it's unlikely to have a problem in the next 30 days or one year based on just how low that high sense of high-sensitivity cardiac troponin result is. And I've been a strong advocate for using these tests in that way for some time. But the limitation has been that much of the work in this field has been observational. And so the patients were actually managed accordingly because of uncertain pathways. And there's always been some uncertainty as just how effective they are when in clinical practice, whether using these approaches are safe. And so we designed the Historic Trial to address that definitively in our hospitals in Scotland. Dr. Greg Hundley: Very nice Nick. So what was the study population and what was the design for this Dr. Nicholas Mills: Thanks Greg. So we use an interesting study design set wage cluster, randomized controlled trial, where rather than randomizing individual patients and randomized hospitals in Scotland, in order to do a trial like this, you need very detailed infrastructure because we wanted to enroll every consecutive patient, attending our emergency departments with symptoms, suspicions of acute cardiac syndrome. We embed it so into our care path, which allows our clinicians to enroll patients for us. We were keen to enroll all consecutive patients because we wants to be confident that our findings were truly generalizable at any included patients with complex comorbidities presenting that of ours who were sick unwell, which is often not the case; they've been observational studies. We randomized hospitals and follow up patients with acute coronary syndrome up for a year in order to determine whether the implementation of already changed clinical care and that was safe and did not lead to recurrent and in the future. Dr. Greg Hundley: Very nice. So Nick, in this randomization of hospitals, how many total patients did you encounter and then what were your study results? Dr. Nicholas Mills: So we enrolled 31,492 consecutive patients. I've crossed all seven hospitals implementing our early relapse pathway, reduced length of stay overall in the hospital. By just over three hours, we increased the proportion of patients who are directly discharged home from the emergency department by more than 50%. So that overall 71% of patients attending hospital with possible acute coronary syndrome were able to be discharged from the emergency department rather than being admitted unnecessarily for further investigations. But the critical result was, was that major change in the care pathway safe. We had a non-inferiority design. We had a very small number of safety outcomes at 30 days, and it was difficult to prove non-inferiority, but the event rate favored the implementation there. Dr. Nicholas Mills: They will have pathway with the 0.4% of patients we attend within 30 days of heart attack or dying from heart disease for our implementing it and 0.3% in and crucially, we followed everyone up for a year and were able to demonstrate that the safety outcome was not increased in those that we are able to that pathway one year with absolute confidence. And furthermore, there was no difference in re attendance or an all-cause mortality. We the two different arms of the trial. So we concluded that the early relapse pathway was effective and safe, and that using this approach we'd have major benefits from patients who can avoid unnecessary for healthcare providers in terms of reducing actual cost limitations. Dr. Greg Hundley: Fantastic. Well listeners, we're now going to turn to our guest editor, Dr. Alan Jaffe, and Alan, could you help us put into perspective these new data regarding high sensitivity, proponent, and also comment what attracted you to this article so much so that you feel it's needs to be published and circulated worldwide in the literature? Dr. Allan Jaffe: One of the important areas in the field of biomarkers is the movement just finally occurring. And Nick has been the forefront of this, of starting to do randomized trials. Observational data is just that it's observational. The patients are not created based on the information that is by the biomarkers. Patients can be missed if you're missing a sample, you exclude those patients. In addition, most observational trials, try and get informed consent. And by getting informed consent often miss the sickest patients. So what's desperately needed by the field. And which is just now starting with two or three ongoing randomized trials is just that a randomized trial where the investigators are forced to use the data, to manage the patient. And by using the step wedge design that Nick and his group has used in other trials as well, they guarantee that they don't miss patients either. Dr. Allan Jaffe: So that it's comprehensive and takes all into account. This is terribly important to then validate things like in this instance, the rule-out pathway. And I think these data do substantially confirm the fact that a single sample rule-out strategy using the cutoff value that Nick had previously established as optimizing the percentage of the population that can be included works well. It is unfortunate that the way in which they design their trial mist and design their non-inferiority outcome for safety was such that they ended up not finding significance to that. But I agree with Dr. Mills in the sense that the outcome adverse effects were so low, that despite that I think there's very important and reasonable data that this strategy is also safe. Dr. Greg Hundley: Very good. Well, Nick, thinking forward, what do you feel is the next study that needs to really be performed in this area? Dr. Nicholas Mills: I completely agree with everything Alan said. I think there's lots of really interesting approaches to find a group diagnosis, risk stratification of this really common condition. We need trials that demonstrate these approaches actually influence care and outcomes. For me, the challenge remains how to really harness these great tests to route the ruler of my cognitive function. I run about ads of patients with elevated cardiac troponin added due to an underlying condition that is an acute coronary syndrome. And we're starting to think about ways in which we can individualize our decision-making a little bit moving to walk away from binary thresholds, because values are influenced by age, by sex, by comorbidities like renal disease and preexisting heart failure about heart disease. Dr. Nicholas Mills: And by incorporating some of these patient factors into the interpretation of cardiac troponin. I think we can give clinicians better guidance on who to treat early with antiplatelet therapies and who needs invasive investigation than just simply saying that the troponin concentration is all positive or negative. And it's our challenge, I think, is how to harness that information, make it workable in clinical practice, and then demonstrate that by doing so we actually target effective therapies better, and that it makes a difference for patient care. So this is where we're working on at the moment. And I hope that in due course, we'll be able to do randomized trials in this space and that will move things forward again. Dr. Greg Hundley: Alan, do you have anything you'd like to add to that? Dr. Allan Jaffe: Yes. I think we're in a new era. We are finally starting to see there are now two or three randomized trials. It is time that the biomarker diagnostic studies graduate to a higher level of evidence, meaning randomized controlled trials. Nick is leading the way in that regard and I suspect and hope that subsequent trials, although observational trials may help inform which ones we should do, but that subsequent trials will continue to be randomized and generate the more robust data that randomized trials are capable of generating. Dr. Greg Hundley: Well, thank you both. And Nick, thank you for bringing us this research and also Alan, for evaluating it and providing this commentary today. It's quite exciting to have really this new information produced from a randomized trial, which evaluated the utility of a low high sensitivity treponema value in patients presenting to hospitals with chest pain syndromes. Well, on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week on the run. This program is copyright of the American Heart Association 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association for more visit ahajournals.org.  

Larry and Mike interview Dr. Juan Granada, a world-renowned cardiologist and CEO of the Cardiovascular Research Foundation, an organization on the leading edge of the battle against heart disease. Heart disease is the leading cause of death among men and women over the age of 50, and Dr. Granada explains the additional risks posed by COVID-19. He also discusses the importance of mask-wearing and social distancing to reduce the risks of contracting the virus and suffering heart damage.

Dr Carolyn Lam:                Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the Journal and its editors. We're your cohosts. I'm Dr Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley:             I'm Greg Hundley, Associate Editor of Circulation, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr Carolyn Lam:                Greg, guess what? We are going to be talking later about non-inferiority trials. Now, you're going to go like, "Huh? What?," but then we see more and more non-inferiority cardiovascular trials. And do we really know the advantages and limitations of this type of trial design? Which is so important to understand, because we need to understand the factors that may impact our confidence and interpretation of these results. So, that's going to be a really important feature discussion, coming up right after our coffee chat. Greg, what are your papers? Dr Greg Hundley:             Thanks Carolyn. Boy, I can't really wait to get to that feature discussion. That's something that we deal with all the time, and I look forward to that explanation and that discussion. I'm going to talk a little bit of basic science, with two papers right in a row.                                                 And the first one involves catecholaminergic polymorphic ventricular tachycardia through inhibition of calcium/calmodulin-dependent kinase II. The lead author is Dr Vassilios Bezzerides from Boston Children's Hospital.                                                 Carolyn, this paper focuses on treatment of catecholaminergic polymorphic ventricular tachycardia, an underlying diagnosis in at least 12% of pediatric patients who present with unheralded cardiac arrest. ICDs, as you know, are frequently implanted, but are problematic because of increased complication rates in pediatric patients, failure to convert ventricular arrhythmias, and the risk of fatal ICD-induced electrical storm. Modulating CaM Kinase II within the heart shows promise to treat this, but CaM Kinase II is essential in other tissues, most notably the brain. Dr Carolyn Lam:                How interesting. So, what did the study show? Dr Greg Hundley:             Well, the investigator used adeno-associated viral gene therapy, which is proven to be a safe and efficient vector for sustained gene transfer into many cell types to selectively inhibit CaM Kinase II in cardiomyocytes. They were able to express the specific CaM kinase II inhibitory peptide AIP in cardiomyocytes without significant extra cardiac expression, and an inhibition of CaM Kinase II effectively suppressed ventricular arrhythmias in a murine model of catecholaminergic polymorphic ventricular tachycardia after a single therapeutic dose. So thus, in animal models, delivery of a CaM Kinase inhibitory peptide by AAV represents a novel single dose gene therapy for catecholaminergic polymorphic ventricular tachycardia. How about that? Dr Carolyn Lam:                Wow. You've got a second paper? Dr Greg Hundley:             I sure do. So now we're going to jump into, again, looking at polymorphic VT from engineered human heart tissue. And this article is from Kevin Parker at Harvard University, "Modeling of Human Arrhythmias Using Induced Pluripotent Stem Cell-Derived Cardiomyocytes has Focused on Single-Cell Phenotypes."                                                 With this said, it is important to realize that arrhythmias are emergent properties of cells assembled into tissues and the impact of inherited Arrhythmia mutations on tissue level properties of human heart tissue. And therefore, newer technologies are needed to develop more satisfactory therapeutic interventions. Ones that encompass all of the tissue, not just single cells. Dr Carolyn Lam:                Interesting. So, what did this particular study do? Dr Greg Hundley:             So, Carolyn, in this study, the investigators report on an optogenetically-based human-engineered tissue model of catecholaminergic polymorphic VT, which as we have discussed in the previous article is promoted by mutation of the cardiac ryanodine channel 2, which is promoted by mutation of cardiac ryanodine channel and triggered by exercise. They developed a human IPSC cardiomyocyte-based platform to study the tissue level properties and investigated pathogenic mechanisms in polymorphic VT by combining this novel platform with genome editing. The authors found that engineered heart tissue, fabricated from human pluripotent stem cell derived cardiomyocytes, effectively modeled catecholaminergic polymorphic VT caused by dominant mutations in the cardiac ryanodine receptor, including induction of arrhythmias by conditions that stimulate exercise. Using selective pharmacology and genome editing, the authors identified activation of calcium/calmodulin-dependent kinase II, or CaM Kinase II, and CaM Kinase II mediated phosphorylation of ryanodine at Serine 2814 as critical events that are required to unmask the latent arrhythmic potential of catecholaminergic polymorphic VT, causing ryanodine mutations, highlighting a molecular pathway that links beta adrenergic stimulation to arrhythmogenesis in this disease. Dr Carolyn Lam:                Wow Greg! So, two very interesting and important linked genetic papers. Well, we're going to switch tracks a little bit and talk about, well, my favorite topic: heart failure with preserved ejection fraction and the whole complex issue of the diagnosis of this syndrome. Now we know that the diagnosis is kind of complex and there is currently no consensus but several proposed definitions. So how do the clinical and hemodynamic profile of patients vary across the different definitions of HFpEF?                                                 So, this question was answered by Dr Jennifer Ho from Massachusetts General Hospital and her colleagues, who examined consecutive patients with chronic exertional dyspnea and an ejection fraction above 50% who are referred for comprehensive cardiopulmonary exercise testing with invasive hemodynamic monitoring. They applied societal and clinical trial HFpEF definitions and compared the clinical profiles, exercise responses, and cardiovascular outcomes by these different definitions. So, of 461 patients, 416 met the ACC/AHA definition, 205 met the ESC definition, and 55 met the HFSA criteria for HFpEF.                                                 The clinical profiles and exercise capacity varied vastly across the definitions, with peak oxygen uptake averaging 16.2 for those with the ACC/AHA definition and down to 12.7 in those satisfying the HFSA definition. Dr Greg Hundley:             Wow. What a difference from these societies. Dr Carolyn Lam:                Mm-hmm (affirmative). Dr Greg Hundley:             So Caroline, it sounds like they looked at all comers with exertional dyspnea. Now how about those that had hemodynamic evidence of heart failure with preserved ejection fraction? Dr Carolyn Lam:                Yeah, good question Greg. So, you caught me telling you that all these patients had hemodynamic cats as well, and a total of 243 had hemodynamic evidence of HFpEF, which was defined as an abnormal rest or exercise feeling pressure. Of these, 222 met the ACC/AHA criteria, 161 met the ESC criteria, and only 41 met the HFSA criteria. Over a mean follow-up of 3.8 years, the incidents of cardiovascular outcomes range from 75 for the ACC/AHA criteria to 298 events per thousand-person years for the HFSA criteria.                                                 The application of clinical trial definitions of HFpEF similarly resulted in distinct patient classification and prognostication. So in summary, the authors demonstrated significant diversity in the number of patients meeting HFpEF criteria. And using different HFpEF classifications variably enriched for future cardiovascular events, but at the expense of not including up to 85% of individuals with physiologic evidence of HFpEF. Comprehensive phenotyping of patients with suspected heart failure really highlighted the limitations and heterogeneity of current HFpEF definitions and may help to refine HFpEF sub-grouping to test therapeutic interventions. Now, these are all discussed in an important accompanying editorial by Michele Senni, Sergio Caravita, and Walter Paulus. Dr Greg Hundley:             Wow Carolyn. It appears, depending upon the definition, we could really classify patients drastically differently. Dr Carolyn Lam:                Yeah, an important paper indeed. And again, I would strongly encourage everyone to read that editorial as well. For my second pick, we're going to switch to CPR in children.                                                 So these authors, now led by Dr Rohan Khera from UT Southwestern, examined the prevalence and predictors of survival of children who progress from bradycardia to pulselessness in in-hospital cardiac arrest despite cardiopulmonary resuscitation. So they looked at almost 5,600 pediatric patients age more than 30 days to under 18 years of age, who received CPR at hospitals participating in the Get With The Guidelines - Resuscitation during 2000 to 2016 each CPR event was classified as bradycardia with pulse, bradycardia with subsequent pulselessness, and initial pulseless cardiac arrest. And the authors assessed for risk adjusted rates of survival to hospital discharge. Dr Greg Hundley:             So Carolyn, what did they find? This is really interesting. Dr Carolyn Lam:                Well, among hospitalized children in whom CPR was initiated, half had bradycardia with poor perfusion at the initiation of chest compressions and nearly one third of these progressed to pulseless in-hospital cardiac arrest despite CPR. Survival was significantly lower for children who progressed to pulselessness despite CPR compared to those who were initially pulseless. So, these findings suggest that pediatric patients who lose their pulse despite CPR are at particularly high risk and require a renewed focus on post resuscitation care. Dr Greg Hundley:             Very interesting, Carolyn. Dr Carolyn Lam:                Well, that wraps it up for our discussion. Let's go onto the featured discussion. Shall we, Greg? Dr Greg Hundley:             You bet. Dr Carolyn Lam:                Non-inferiority cardiovascular trials are increasingly being published and in the highest impact journals. Yet how much do we really know about these designs of the trial, of the non-inferiority trials? Well, I have to admit not much in my point of view, and I was so pleased to see our feature discussion paper really published in this week's journal, which really digs deep into non-inferiority trials and talks about time trends and perhaps some lessons that we should all bear in mind when we look at these. I'm so pleased to have the first author, Dr Behnood Bikdeli, to tell us about the study. And he is from Columbia University Medical Center, New York Presbyterian Hospital, Yale Center of Outcomes, Research and Evaluation Core, as well as the Cardiovascular Research Foundation in New York. We also have Dr Naveed Sattar, associate editor from the University of Glasgow. Behnood, could you tell us, so what made you look at this question and what did you find? Dr Behnood Bikdeli:        For a while we've been very interested in profiling the cardiovascular trials, trying to understand a little better, what are the specific characteristics of the major child that we rely upon for research but also for clinical practice? Years ago, we did some studies for surrogate outcome trials and this, let's just say subsequent piece, where we tried to look into a randomized cardiovascular trial that use a non-inferiority design. We had a series of features in terms of quality metrics and methodological metrics that we wanted to look into. The over eight almost 27-year period, we identified 111 of these trials. Reassuringly, most of these trials inherited several important quality and methodological metrics that we were looking into. However, we also saw a significant room for improvement. There were quite a few quality or methodological metrics that some of these trials were not adhering to and we think it's important because ultimately for the design reporting and last reading of these trials, knowing these pluses and minuses would help inform people. Dr Carolyn Lam:                That's great, Behnood. Now for those of us listening who don't think about this every day, could you give us some examples of the top errors perhaps to look out for? Dr Behnood Bikdeli:        For example, in the typical superiority trials, when we want to test an intervention a versus intervention B, all that matters is we do a very good and adequately sized trial and rest of it is up to the study and how it goes to see whether or not something panned out. There was a significant difference between the new intervention versus the older ones, but in non-inferiority trials we have something called the non-inferiority margin and that's very highly relevant when it comes to the outcome that you're assessing when it comes to the ultimate results of the trial.                                                 If the investigators choose a very lenient y non-inferiority margin, they may end up calling an intervention non-inferior. They may give it a pass. While in reality the intervention has quite a lot of a risk or harmful profile compared with standard of care. But in the other side, as a clinical example, we have several interventional tools at hand, like transcatheter aortic valve replacement. Most of the indications where it's currently used came from large bell designed non-inferiority trials. Where they showed that it was almost as good as surgery, in some cases better, but also it had a lot of ancillary advantages. Dr Carolyn Lam:                Thanks, Behnood. And you know here, I just want to call out to the readers. You have to look at this paper. Look at the tables and figures which are really so helpful. And Naveed, can I bring you in on this now? I mean, I just love this paper. It's such an important topic and I've never seen it addressed like this before. Could you tell us a little bit about what the editors discussed when we looked at this? Dr Naveed Sattar:            I've been involved in a few non-inferiority trials and some of the factors that many of us discuss and some of course associated, sort of our clinical trials, and I've been involved normally in superiority trials, but increasingly we have cut our teeth in non-inferiority trials. So, some of the points that the paper picks up resonated well with us in terms of, one of the examples was Behnood and his team found that around about 40% of trials didn't even justify what their non-inferiority margin was. And that's something I've actually had detailed discussions involved in various trials with. And that's a really important point, but it isn't a, you have to be able to justify why you choose particular margin and what that margin would mean to the community. Otherwise you potentially could just pick something out there which really doesn't allow you to make a really strong non-inferiority claim. And I think that's one of the factors that you found, Behnood. Is that correct? Behnood Bikdeli:              Absolutely. And that's a great point. Thank you. To us, there were two things about it. One was whether or not they provided any detailed justification for it exactly as you said, not that they're just picking up something because that's the sample size that they could achieve or that's the number that they felt comfortable with. But also the second piece of it, a respective of how they calculated or came up to the number, their readers have a right to know how this was calculated or were this came from, so it's the reporting part of it. Sometimes they reported both in the published paper and a study protocol or a design paper. Sometimes it was only in one of them. Sometimes as you mentioned, it was not mentioned in either, which puts the reader in a very difficult situation.                                                 So we think, and these were the best of the best trials in the highest impact journals. Probably if we look high and low elsewhere it's going to be even more challenging. So, we think there's a lot of room for improvement for the readers to expect cleaner, more comprehensive papers to come, but also for the trialist to report them with more clarity. Dr Naveed Sattar:            And going forward, issue a nice figure that shows that the trend is that we are going to see more of these trials probably because you've got lots of better treatments now. So, you know it's getting harder, in the sense, in many areas of cardiovascular medicine to show superiority. So, there is a need for more trials which actually show benefits beyond just perhaps the main outcome in ways that you've explained in the particular paper.                                                 Do you think the FDA does enough in this particular area in terms of this helping investigators decide what the non-inferiority margins are? Or is that something in terms of the quality of the trials that needs a bit more investigation? I think your papers partly are pushed to say, "Actually we need to do these better. We need to justify them better. We need to look at them better." Because actually they do have a greater influence going forward. Dr Behnood Bikdeli:        First, I cannot agree more. We are going to see a lot more of non-inferiority trials sort of, maybe because we have reached a ceiling effect when traditional intervention for superiority, but there's a lot of room to find interventions that are at least as safe or as good but have a lot of side advantages and ancillary benefits that's happened with some of the anticoagulants among other therapies available.                                                 In terms of the regulatory aspects, one of the things we were fortunate about was within our team, we had people with expertise on the trialist side while communicating with the regulatory bodies and also from people who were consulting to the FDA for assessment of non-inferiority trials. So, we were fortunate to look into several of the methodological or quality metrics that were being thought of and we consulted with the in-source guidelines and FDA guidelines. That said, I completely agree that, for example, the suggestions that you provided in one of the tables could hopefully help shape some of these trials in a more rigorous way. Or at least a reporting, which is also an important piece, would be more transparent ultimately for the readership. Dr Naveed Sattar:            Absolutely. And transparency is really pivotal so that the readers completely understand what was done, what was predefined, and what was found so that they can make a proper judgment. And probably the final question I have in terms of, you make a good point that actually if the trials are not done well and there's a bit of slippage either in terms of loss of data or methodological issues, that then really pushes a trial towards a "no", in a sense you get a false reassurance of non-inferiority, but partly because the methodology wasn't robust enough. And it's really very critical for these trials, perhaps at least as critical as they are in superiority trials, but perhaps even more so. Is that a fair judgment? Dr Behnood Bikdeli:        No, no, no. You're absolutely right. That's another very important point in the typical superiority trial, if any bias drives the results toward no difference. Investigators are naturally guarding against that because it's going to be very problematic in non-inferiority trials. Depending on the effect measure that they choose, it could actually falsely favor the intervention of interest because it might show a false assessment of non-inferiority, and there are ways to work around it. There are ways to correct for it, such as choosing both absolute and relative effect measures, which practically addresses this concern. Again, gets back to the importance of appropriate design and appropriate transparency to report the results in a robust way, both intentions to treat and has treated or per protocol, both relative effect measures and absolute effect measures. Dr Naveed Sattar:            My sense of and getting back to you, but I think this will be a really seminal paper for the community to look at and really help us as a community to improve our conduct of such trials in the future because there will be more of these coming forward. Dr Carolyn Lam:                And I couldn't have said that better, Naveed. I think the take home message is right there. Pick it up, have a look and especially have a look at those tables and figures. It's really going to help you read many, many journals.                                                 Thank you so much, Naveed and Behnood. Thank you audience for joining us on Circulation on the Run. Talk to you next week.                                                 This program is copyright American Heart Association 2019.  

"Blogging is like going to the word gym. I practice writing in the same I would go to a gym to get stronger muscles. Writing is a muscle and I try to stay fit for it. " Is it possible to strive to be a writer and make a living at it? Shelley knew she wanted to be a writer at a young age but how could she make a living doing it? Today is all about making dreams happen.   Shelley quit her job, moved to France for a short period and wrote a book. By the way, she had never written a book of fiction before and had no idea how to do it. She’s going to tell us how she got the idea eventually and how she made it happen.   Shelley's fiction, creative non-fiction, columns, and travel writing have appeared in a range of Canadian and international publications. She won the Fall 2015 Tethered by Letters fiction contest, the 2016 Frank McCourt Prize for Creative Nonfiction, the Winter 2016/2017 Nonfiction prize from Causeway Lit, and the 2017 Fiction prize from Freefall Magazine. The Quintland Sisters, her debut novel, will be published in Canada and the United States in March of 2019. You can order or pre-order depending on when you listen to this, at shelleywood.ca  Born and raised in Vancouver, Shelley divides her time between a full-time home in Kelowna, Canada, and a full-time job in New York, NY, where she is the Editorial Director at the Cardiovascular Research Foundation and Managing Editor at the cardiology news website, TCTMD.   With that, let’s listen in and gear up for what’s next.  Where to Find Shelley Instagram Her website BEFORE YOU LEAVE - If you are enjoying the shows, I hope you’ll subscribe, rate, review and share with your friends!  About Lisa Gerber: Lisa advises CEOs and senior level management on how to use the power of storytelling and effective communication to influence action and bring ideas to life.  She guides companies through the digital maze of constantly changing tools to build discovery, loyalty, and ultimately help them achieve their own big leaps.  When she is not in her office, she might be out skiing or trail running. This is where she does her best creative problem-solving. To learn more about booking Lisa for consulting, speaking or workshops, visit www.bigleapcreative.com.

  Carolyn: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore.     In just a moment, we are going to be discussing the feature paper on results of the RE-LY trial in patients with valvular heart disease. Yes, you heard me right, this means dabigatran versus warfarin in patients with atrial fibrillation and valvular heart disease. You need to listen to this discussion with first author Dr. Michael Ezekowitz, but first here is a summary of this week's issue.     In the first study, Dr. Norby and colleagues from the School of Public Heath University of Minnesota assessed trajectories of cardiovascular risk factors and the incidence of atrial fibrillation over 25 years in the ARIC study or the Atherosclerosis Risk in Communities Study. They first assessed the trajectories of cardiovascular risk factors in more than 2,400 individuals with incident atrial fibrillation and more than 6,400 matched controls. Next, they determined the association of those risk factor trajectories with the incidence of new atrial fibrillation among more than 10,500 individuals free of atrial fibrillation at baseline.     The main finding was that stroke, myocardial infarction and heart failure risk increase steeply during the time close to diagnosis of atrial fibrillation. All cardiovascular risk factors were elevated in atrial fibrillation cases compared to controls more than 15 years prior to the diagnosis. A trajectory analysis showed not only the presence of the risk factors such hypertension and obesity, but also their duration which was more informative in determining the risk of atrial fibrillation compared to a one time clinical measurement.     Finally, they identified diverse and distinct trajectories for the risk factors findings that carry implications for the different roles of different risk factors in the pathogenesis of atrial fibrillation. The findings of this very significant study also highlight the need to establish preventive strategies that address risk factors decades before atrial fibrillation diagnosis.     The next study is by first author Dr. van der Valk and corresponding author Dr. Strauss from the Academic Medical Center in Amsterdam. These authors aimed to better understand the underlying mechanisms responsible for atherogenicity of lipoprotein a or LPa. The authors achieved this aim by a combination of three approaches. First, in vivo magnetic resonance imaging using 18F-FDG PET/CT and SPECT to measure atherosclerotic burden, arterial wall inflammation and monocyte trafficking to the arterial wall. Secondly, ex vivo analysis of monocytes using facts analysis, inflammatory stimulation assays and trans endothelial migration assays. Third, in vitro studies on monocytes using an in vitro model for trained immunity.     Their main findings were that, firstly, individuals with elevated LPa had increased arterial wall inflammation in vivo. Secondly, that monocytes from these individual remain in a long lasting activated state ex vivo, and finally, that LPa elicited a pro-inflammatory response in healthy monocytes in vitro, an effect that was markedly attenuated by removing or inactivating oxidized phospholipids on LPa.     In summary, this study nicely shows that LPa induces monocyte trafficking to the arterial wall and mediates pro-inflammatory responses through its oxidized phospholipid content. The clinical implications are therefore, that oxidation's specific epitope targeted therapy using for example specific antibodies as single gene antibodies may bear clinical potential to modulate the arthrogenic impact of LPa.     The final study is from first author Dr. Mazen, and corresponding author Dr. Ouzounian from Toronto General Hospital and University of Toronto in Ontario, Canada. These authors sought to compare the long term outcomes of patients undergoing the Ross procedure compared to mechanical aortic valve replacement in a propensity match cohort study of 208 pairs followed for a mean of 14 years.     They found long term survival and freedom from re-intervention were comparable between the Ross procedure and mechanical aortic valve replacement. Of note however, the Ross procedure was associated with improved freedom from cardiac and valve related mortality, as well as a significant reduction in the incidence of stroke and major bleeding. This paper provides important evidence that supports continued used of the Ross procedure in properly selected young adult patients in specialized centers.     What this means is having experienced surgical teams dedicated to mastering the technique and committed to carefully following up the patients for possible late complications. This and more is discussed in a provocative editorial by Dr. Schaff from Mayo Clinic Rochester, Minnesota who provocatively entitled his editorial 'The Ross Procedure: Is it the Preferred Procedure or Double, Double Toil and Trouble?'     Those were all summaries, now for our featured paper.     I am so excited to be joined from all over the world to discuss the featured paper today, and that is on the comparison of dabigatran versus warfarin in patients with atrial fibrillation and valvular heart disease. To discuss this first we have, first and corresponding author, Dr. Michael Ezekowitz from the Sidney Kimmel Medical College at Thomas Jefferson University and Lankenau Medical Center in Philadelphia, as well as from the Cardiovascular Research Foundation in New York. Welcome Michael.   Michael: Thank you very much.   Carolyn: Michael, you're calling from South Africa aren't you?   Michael: I am indeed.   Carolyn: That's wonderful. We're very honored to have Dr. Shinya Goto Sensei, Associate Editor of Circulation from Tokai University Japan. Hello Shinya.   Shinya: Hello Carolyn, thank you very much for your invitation to such an excited podcast. I enjoy podcast every week.   Carolyn: I love this and it is extremely exciting and the most global discussion that we have had so far, with calling in Japan and Singapore and South Africa. Indeed it's because we're discussing a very important problem globally. Michael first, when we talk about the RE-LY trial and the NOAC trials, we're always associating them with non-valvular atrial fibrillation, and yet your topic is discussing valvular heart disease from RE-LY. Can you please start by clarifying that?   Michael: I think the reason we wrote this paper is that there is a misunderstanding of the patient populations that was studied in all the NOAC trials because they were characterized as having non-valvular atrial fibrillation. That's only partially true because in all the trials, patients with mechanical heart valve and hemodynamically significant mitral stenosis were excluded, and yet there were many patients with valvular disease that were included. In the RE-LY trial which is the focus of this particular paper, 25% of the patients had some form of valvular disease that were recruited into the study. So the term non-valvular is misleading.   Carolyn: That is such an important clarification, and it's an issue that I see a lot in Singapore. Frankly, lots of patients with atrial fibrillation have some valve disease even if you exclude prosthetic valves, significant mitral stenosis or valvular heart disease requiring intervention. We're very clear not that this is the patient population you're referring to. Shinya, I want to bring you into this. I see lots of these patients, how about you?   Shinya: The same. Majority of patients have valvular heart disease, small mitral regurgitation is very common. We are excluding only clinically overt mitral stenosis and basically mechanical heart valve in all the newest trials. As Michael pointed out, it is very important to correct misunderstanding. Non-valvular atrial fibrillation, we used in the clinical trial is all atrial fibrillation except clinical overt mitral stenosis and prosthetic for mechanical heart valve.   Carolyn: Exactly. A great foundation for us to get our understand right before we discuss the findings. Michael, could you please give us the top line result and tell us what do the results mean for your own clinical practice?   Michael: Basically, it means that the patients with valvular heart disease that were included in the trial, and these included patients with mitral regurgitation with was the most common lesion, mixed aortic valve disease, tricuspid regurgitation, and also it turned out that there were 192 patients that had mild mitral stenosis. Those with mitral stenosis were presumed to be rheumatic in ideology, and they did have a profile of having rheumatic heart disease, that there were more females, they were younger, there was a high incidence of heart failure and a high incidence of TIA and stroke.     The bottom line here is whether the patients had mild mitral stenosis or the other forms of valvular disease that I just mentioned, that they benefited in an identical fashion from the 150 milligram BID dose of dabigatran and the one 110 milligram BID dose of dabigatran as those patients without any valvular disease. The bottom line is that clinicians can use dabigatran with equal confidence in these patients with valvular disease as in patients without valvular disease.   Carolyn: Thank you Michael, that was very reassuring and something that is very clinically important. Shinya, I'm going to ask a different question. First, maybe your take on the findings, and secondly, what was it like handling this paper across the globe as the Associate Editor Managing this?   Shinya: That is a very important point. The past as Michael pointed out, this paper is very important to remind the clinician of non-valvular atrial fibrillation is not really non-valvular atrial fibrillation, and there is no difference between valvular atrial fibrillation except mitral stenosis and prosthetic valve. The result is similar to non-valvular atrial fibrillation in regard to the effect of dabigatran or by warfarin. That is the one point I have to assure. As a part, it is very important. We are now including many patients not limited in that North America, Europe. We are participating a huge number of patients from Asia. The results is applicable to the global level. We are now leading in that global evidence-based world and RE-LY is one of the good example for the global trial testing the hypothesis with [inaudible 00:13:58] over warfarin.     Michael made a very good summary of that, not only limited to RE-LY, he talked about as our trial like ARISTOTLE and the ROCKET trial. All of the NOAC trial include patient who is valvular heard disease, and the exclusion criteria is a little bit different. Michael beautifully summarized that difference in the table, in his paper.  There is a strong intention to publish this paper integration from all the editorial of old member. This is a very nice paper.   Michael: He's been very kind, that's very nice. That's true. In fact, the results in RE-LY were compared in an indirect fashion with the other trials, ROCKET and ARISTOTLE, through have published similar papers on patients with and without valvular heart disease. Just in summary, the bottom line is that this finding in RE-LY is highly reproducible in the other two trials so this is an important finding that is reproducible and true of the three novel agents that had looked at this in detail.     The other point that was raised is that there were differences in the exclusion criteria in these trials, but at the end of the day, the Europeans and the Americans in terms of guidelines, had fairly similar recommendation. For instance in the United States, it was felt that all patients with valvular disease could be anti-coagulated with the novel agent unless they had rheumatic mitral stenosis, mechanical or bioprosthetic heart valves, or patients that had undergone a prior mitral valve repair. The emphasis was that all other patients could be included.     The Europeans differed slightly and that they agreed that mechanical prosthetic valve and moderate to severe mitral stenosis should be excluded, but they were somewhat more global in recommending inclusions of all other valvular conditions. There is a slight difference then between the European and the American recommendations and guidelines.   Carolyn: On that note of looking across the world at the guidelines and what these results mean, it really leaves me to congratulate you Michael on such an excellent paper, and Shinya for just managing this paper so well.   Michael: Thank you.   Shinya: Thank you very much for your invitation. Bye-bye.   Carolyn: You've been listening to Circulation on the Run. Thank you for joining us today.    

Jack Lewin, MD CEO of Cardiovascular Research Foundation was Interviewed Live on 640WGST Talk Radio Atlanta's Health Tech Talk Live Hosted by Ben Chodor -- February 21, 2015 ARCHIVE Interview Aired at 3:30pm ET / 12:30pm PT / 2:30pm CT on Health Tech Talk Live Radio Show, Hosted by Ben Chodor. Show Broadcasts weekly on Talk Radio 640 WGST Atlanta. Public Relations and Marketing by http://1800publicrelations.com ("1800pr"), The Leader in Performance based PR and Marketing Services. To inquire about being a guest on this show or others: Matthew Bird 1800 Public Relations ("1800pr") 917-409-8211 matt.bird@1800pr.com Twitter: @1800pr http://www.640wgst.com/main.html http://www.640wgst.com/articles/health-tech-talk-490191/health-tech-talk-13092706/ http://healthtechtalk.com/ Twitter: @HealthTech_Talk

Host: Janet Wright, MD Guest: Gary Mintz, MD Acute coronary syndromes in patients who have undergone percutaneous coronary intervention is the subject of the conversation between guest Dr. Gary Mintz, chief medical officer of the Cardiovascular Research Foundation, an independent, academically focused nonprofit organization dedicated to improving the survival and quality of life for people with cardiovascular disease through research and education, and host Dr. Janet Wright. How often do patients who have an acute coronary syndrome have a recurrent event? Their discussion includes protocols, paramaters and outcomes of the PROSPECT trial. The use of ultrasound as well as angiography are also discussed in context to help identify unstable coronary plaques in order to prevent adverse coronary events.

Host: Janet Wright, MD Guest: Gary Mintz, MD Acute coronary syndromes in patients who have undergone percutaneous coronary intervention is the subject of the conversation between guest Dr. Gary Mintz, chief medical officer of the Cardiovascular Research Foundation, an independent, academically focused nonprofit organization dedicated to improving the survival and quality of life for people with cardiovascular disease through research and education, and host Dr. Janet Wright. How often do patients who have an acute coronary syndrome have a recurrent event? Their discussion includes protocols, paramaters and outcomes of the PROSPECT trial. The use of ultrasound as well as angiography are also discussed in context to help identify unstable coronary plaques in order to prevent adverse coronary events.

Host: Alfred Bove, MD Guest: Gregg Stone, MD Results of a recent study may change the standard of care for patients with acute coronary syndromes. Although clopidogrel is generally the antiplatelet therapy of choice for patients for whom an invasive strategy is planned for treating their acute coronary syndromes, bleeding can be of concern. Prasugrel often presents the same dilemma. Enter, ticagrelor. The PLATelet inhibition and patient Outcomes, or PLATO, trial compared ticagrelor and clopidogrel, which demonstrated promising results for ticagrelor. Dr. Gregg Stone, professor of medicine and director of research and education at the Center for Interventional Vascular Therapy at the Columbia University Medical Center, and director of medical research and education at the Cardiovascular Research Foundation in New York City, hails the PLATO findings as transformative to the standard of care for acute coronary syndromes. He joins host Dr. Alfred Bove to discuss the new place of ticagrelor among the antiplatelet therapy options.

Host: Alfred Bove, MD Guest: Gregg Stone, MD Results of a recent study may change the standard of care for patients with acute coronary syndromes. Although clopidogrel is generally the antiplatelet therapy of choice for patients for whom an invasive strategy is planned for treating their acute coronary syndromes, bleeding can be of concern. Prasugrel often presents the same dilemma. Enter, ticagrelor. The PLATelet inhibition and patient Outcomes, or PLATO, trial compared ticagrelor and clopidogrel, which demonstrated promising results for ticagrelor. Dr. Gregg Stone, professor of medicine and director of research and education at the Center for Interventional Vascular Therapy at the Columbia University Medical Center, and director of medical research and education at the Cardiovascular Research Foundation in New York City, hails the PLATO findings as transformative to the standard of care for acute coronary syndromes. He joins host Dr. Alfred Bove to discuss the new place of ticagrelor among the antiplatelet therapy options.