Podcasts about stemis

In this standout episode of Next Steps 4 Seniors: Conversations on Aging, we’re bringing back an audience favorite: our eye-opening interview with Nurse Practitioner Liz Jackson from Henry Ford Hospital. Liz breaks down the B.E.F.A.S.T. method for spotting stroke symptoms early, dives into the different types of strokes, and explains why timing is everything when it comes to treatment. We also tackle the red flags of heart attacks, the sneaky signs of vascular disease (yes, even leg cramping!), and how managing conditions like high blood pressure and diabetes can be game-changers. Early detection = lives saved. This episode is packed with info that could protect you or someone you love. Listen now on your favorite podcast platform! Follow us on Facebook and Instagram @ConversationsOnAging Visit nextsteps4seniors.com and our foundation at nextsteps4seniorsfoundation.org Questions or ideas? Call 248-651-5010 or email hello@nextsteps4seniors.com Sponsorship inquiries: marketing@nextsteps4seniors.com Sponsored by Aeroflow Urology: You could qualify to receive incontinence supplies at no cost through insurance—discreetly delivered to your door. Visit aeroflowurology.com/ns4s to check eligibility. (*Some exclusions apply.)Learn more : https://nextsteps4seniors.com/See omnystudio.com/listener for privacy information.

In this episode of Next Steps 4 Seniors: Conversations on Aging, we sit down with Nurse Practitioner Liz Jackson from Henry Ford Hospital to discuss life-saving information on strokes, heart attacks, and vascular health. We break down the B.E.F.A.S.T. method for identifying stroke symptoms early, explore the different types of strokes, and highlight the urgency of seeking immediate medical attention. Elizabeth also shares insights on recognizing heart attack warning signs, managing key risk factors like high blood pressure and diabetes, and understanding how leg cramping may indicate vascular disease. Early detection and fast action can save lives—tune in to learn how you can protect yourself and your loved ones.

The JournalFeed podcast for the week of Sept 9-13, 2024.These are summaries from just 2 of the 5 articles we cover every week! For access to more, please visit JournalFeed.org for details about becoming a member.Monday Spoon Feed:There are an increasing number of water bead related injuries in children, with the majority occurring in children less than five. While most cases can be treated and released from the ED, water bead injury can be serious and even deadly.Friday Spoon Feed:These researchers developed and trained a deep ensemble artificial intelligence (AI) model to classify ECGs as STEMI versus non-STEMI. The AI performed well in both accuracy and in improving sensitivity.

Matt and Will continue discussing the use of fibrinolytics with several other disease processes we commonly see in emergency medicine. This includes STEMIs and pulmonary emboli. As we go through the uses and dosing Will and Matt talk about some of the indications and thought processes that go into using these medications and when to pull the tirgger on utilization.  This is part 2 of 2 with fibrinolytic use.  As always, please feel free to email us at MCESEducation@umc.edu for any questions, comments, or concerns with our podcast.

CardioNerds co-founder Dan Ambinder joins Dr. Lefan He, Dr. Sina Salehi Omran, and Dr. Neil Gupta from the University of Rochester Cardiovascular Disease Fellowship Program for a day sailing on Lake Ontario. Expert commentary is provided by Dr. Jeffrey Bruckel, and CV Fellowship Program Director Dr. Burr Hall shares insights on the University of Rochester fellowship. The episode audio was edited by CardioNerds intern Dr. Atefeh Ghorbanzadeh. They discuss the following case involving a patient with papillary muscle rupture. This is a 63-year-old man with hypertension, hyperlipidemia, and active tobacco smoking who presented with acute dyspnea. He was tachycardic but otherwise initially hemodynamically stable. The physical exam demonstrated warm extremities with no murmurs or peripheral edema. Chest X-ray revealed diffuse pulmonary edema, and the ECG showed sinus tachycardia with T-wave inversions in the inferior leads. A bedside echocardiogram revealed a flail anterior mitral valve leaflet. The patient was taken for cardiac catheterization that revealed nonobstructive mid-RCA atheroma with a distal RCA occlusion, which was felt to reflect embolic occlusion from recanalized plaque. PCI was not performed. Right heart catheterization then demonstrated a low cardiac index as well as elevated PCWP and PA pressures. An intra-aortic balloon pump was placed at that time. A TEE was performed soon after which showed the posteromedial papillary muscle was ruptured with flail segments of the anterior mitral leaflet as well as severe posteriorly directed mitral regurgitation. The patient ultimately underwent a successful tissue mitral valve replacement and CABG. US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! case Media Pearls - A Case of Papillary Muscle Rupture Most cases of papillary muscle rupture demonstrate only small areas of ischemia with preserved ventricular function, thus causing high shear force on the ischemic papillary muscle. The posteromedial papillary muscle has a single blood supply from the posterior descending artery, while the anterolateral papillary muscle has a dual blood supply from the LAD and the circumflex. Therefore, the posteromedial papillary muscle is more vulnerable to ischemia and, hence, rupture. A murmur may be absent in cases of papillary muscle rupture due to the rapid equalization of left atrial and left ventricular pressures caused by the acuteness of the severe MR. Papillary muscle rupture should always be on the differential for acute dyspnea when ACS is suspected. While mostly associated with STEMIs, mechanical complications of acute myocardial infarctions can also occur after NSTEMIs. Always auscultate patients carefully after a myocardial infarction! When evaluating patients with chest pain presenting with acute or rapidly progressive heart failure and a hypercontractile LVEF should raise suspicion for mechanical complications of MI. Once a papillary muscle rupture is diagnosed, cardiac surgery should be immediately contacted. Temporizing measures prior to surgery include positive pressure ventilation, IV nitroglycerin/nitroprusside, and temporary mechanical circulatory support. Notes - A Case of Papillary Muscle Rupture What is the clinical presentation of acute mitral regurgitation from papillary muscle rupture? Patients typically present 3-5 days after a transmural infarct. Roughly half of these patients present with pulmonary edema that may quickly progress to cardiogenic shock. Most cases are associated with STEMIs, but papillary muscle rupture is also possible with an NSTEMI.

Note to readers: Since going live with Cardiology Trials Substack in January of 2024 we have been exclusively covering trials that we have categorized as belonging to the major subject heading “Acute Coronary Syndrome” belonging to the subsection “Medicines”. Our indexing scheme was described in one of our original posts and we encourage our audience to read it if you have not already. This is pertinent because the next several trials being presented may seem to come out of the blue but we assure you there is a method.N Engl J Med 2007;357:2011-15.Background Up to now we have presented trials involving major foundational medical therapies for acute coronary syndrome which include aspirin, thrombolytic agents and anticoagulation, but not those involving percutaneous coronary intervention (PCI) as they are reserved for another section. But, by the turn of the 21st century, PCI had become the dominant up-front strategy for revascularization in many countries around the world. Clinical trials demonstrated it improved outcomes, the main one being re-infarction, compared to thrombolysis in patients with STEMIs, and there was an evolving evidence for it in non-ST-segment elevation acute coronary syndrome (STEACS) as well, where thrombolysis had not demonstrated any significant benefits.As PCI became dominant, antithrombotic strategies for optimizing outcomes following PCI evolved along with it. These early trials generally involved a mixture of patient phenotypes (acute vs elective PCI) and were relatively small and of limited quality by comparison to many of the seminal trials presented thus far. Instead of presenting each of these smaller studies, we direct readers to a narrative review that nicely describes the evolution of dual-antiplatelet therapy for PCI and other indications.Briefly: dual-antiplatelet therapy with aspirin and ticlopidine, an antiplatelet agent belonging to the drug class of thienopyridines, which inhibits platelet aggregation induced by ADP, was found superior to aspirin alone or aspirin plus anticoagulation when PCI was performed; however, there were concerns about its safety. Clopidogrel was developed after ticlopidine; it had a similar mechanism of action but less safety concerns and could be given as a loading dose to produce more rapid effects. Despite limited evidence from clinical trials comparing it head-to-head with ticlopidine it became the dominant thienopyridine agent on the market and still has a prominent role in the management of cardiovascular diseases today.Following PCI and dual-antiplatelet therapy with aspirin and clopidogrel, patients continue to have an elevated risk of coronary events, in general, and in-stent related coronary events, in particular. Some of this risk has been attributed to limitations of clopidogrel itself. Clopidogrel has modest antiplatelet effects (compared to other thienopyridines) with substantial interpatient variability due to genetic polymorphisms that impact clopidogrel metabolism and antiplatelet efficacy. Clopidogrel also has a delayed onset of action, which is especially relevant regarding its ability to protect against the dreaded adverse event of early in-stent thrombosis.Prasugrel is a thienopyridine—developed after clopidogrel—that inhibits platelet aggregation more rapidly, consistently and to a greater extent. The Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction (TRITON–TIMI) 38 trial sought to test the hypothesis that prasugrel would reduce major cardiovascular events compared to clopidogrel in patients with acute coronary syndrome undergoing PCI.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients Eligible patients had either moderate-to-high risk unstable angina (UA) or NSTEMI or STEMI. UA and NSTEMI were defined by ischemic symptoms lasting 10 minutes or more and occurring within 72 hours before randomization, a TIMI risk score of 3 or more, and either ST-segment deviation of 1 mm or more or elevated levels of a cardiac biomarker of necrosis. STEMI was traditionally defined. Key exclusion criteria included an increased risk of bleeding, anemia, thrombocytopenia, a history of pathologic intracranial findings, or the use of any thienopyridine within 5 days before enrollment.Baseline characteristics The median age of patients was 61 years with 13% being ≥75 years and 74% were men; over 90% were white. The index event was UA or NSTEMI in 74% and STEMI in 26%.  PCI was performed in 99% of patients and split evenly between those receiving bare metal or drug eluting stent(s).  18% of patients had a prior MI, 23% had diabetes, 64% had hypertension and 38% were tobacco users. Only 11% of patients had CKD defined as a creatinine clearance ≤60 ml/min.Procedures A loading dose of prasugrel 60 mg or clopidogrel 300 mg was given in a double blind manner anytime between randomization up to 1 hour after leaving the catheterization laboratory. In order to be randomized, the plan for PCI had to be known. This could occur before going to the cath lab for planned PCI, if the anatomy was already known or occur in the cath lab during the case where anatomy was determined and PCI was performed. If PCI was planned, patients were eligible to undergo pretreatment with the study drug for up to 24 hours prior to PCI.Treating physicians determined the vessels treated, devices used, and adjunctive medication administered to support PCI. After PCI, patients received maintenance doses of either prasugrel 10 mg daily or clopidogrel 75 mg daily. Use of aspirin at a dose of 75 to 162 mg daily was recommended. Study visits were conducted at hospital discharge, 30 days, 90 days, and 3-month intervals thereafter, for a total of 6 to 15 months.Endpoints The primary efficacy endpoint was a composite of cardiovascular death, nonfatal MI or stroke during the follow up period. A prespecified “landmark” analysis was undertaken to compare the primary endpoint event rate up to 3 days following randomization and from day 3 to the end of the study. The sample size calculation was event-driven and it was determined that 875 primary endpoint events would provide 90% power to detect a relative risk reduction of 20%. A prespecified analysis performed after 650 events revealed a lower than anticipated event rate and the investigators increased the sample size accordingly.Results A total of 13,608 patients (10,074 with UA or NSTEMI and 3534 with STEMI), from 707 sites in 30 countries were enrolled. There were 6,813 patients assigned to the prasugrel group and 6,795 assigned to clopidogrel. The median duration of therapy was 14.5 months. Prasugrel significantly reduced the primary composite endpoint compared to clopidogrel (9.9% vs 12.1%; HR 0.81; 95% CI 0.73-0.90; P

Lancet 1996;347:561-68.Background In most of the prior AMI trials presented here, patients with non_ST-segment myocardial infarction (NSTEMI) and/or unstable angina were included with patients with ST-segment myocardial infarction (STEMI). Patients with NSTEMI usually represented about 1/3 of trial participants. It had become clear based on subgroup analyses from the previous trials that NSTEMI patients did not benefit from thrombolysis. So, while intravenous anticoagulation with heparin was not found to be beneficial in GISSI-2 or ISIS-3, where thrombolysis was also used, there remained the possibility that it may benefit patients with unstable coronary syndromes who were not candidates for thrombolytic therapy. This smaller trial represents a departure from the general eligibility criteria for the AMI trials that we have already reviewed. The Fragmin During Instability in Coronary Artery Disease (FRISC) study group sought to test the hypothesis that subcutaneous low-molecular-weight heparin, in combination with aspirin, reduces death and new cardiac events in patients with unstable CAD. For the purposes of this study, unstable CAD represents unstable angina and NSTEMI.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients Patients had to be men older than 40 years and women at least 1 year after menopause admitted to the hospital for chest pain within the previous 72 hours. All patients had to have either newly developed or increased angina symptoms during the previous 2 months or persisting chest pain with suspicion for AMI and at least one of the following ECG criteria: transient or persistent ST depression of ≥ 0.1 mV or T-wave inversion of ≥ 0.1 mV in at least 2 adjacent leads without pathological Q waves in the ischemic leads. Essentially, the authors were selecting patients with unstable angina or NSTEMIs and not STEMIs or completed infarcts. There were many exclusion criteria for the trial including the presence of conditions with an increased risk of bleeding, known renal or liver insufficiency, indications for thrombolysis, suspected myocarditis and many others; however, it is worth noting there was no upper age limit.Baseline characteristics There were 5,137 patients who met eligibility criteria and 1,506 (29%) were randomized. The 3 most common reasons for exclusion were risk of bleeding (20%), compliance problems (15%), and Q waves or bundle branch block (14%). Patients with other severe disease accounted for 4% of exclusions and those with renal or liver insufficiency accounted for 2%.The median age of participants was 69 years and approximately 65% were men. 20% of participants were active smokers, 13% had diabetes and nearly 30% had a previous heart attack. Patients with NSTEMI accounted for close to 40% of participants and the remainder had unstable angina.Procedures Treatment was started as soon as possible after admission. During the first 6 days (acute phase), 120 IU per kg bodyweight (maximum dose of 10,000 IU) of dalteparin or placebo was injected every 12 hr. There was then a home treatment phase. For the next 35-45 days—at home— 7,500 IU of dalteparin or placebo was injected once daily. Patients stayed in the hospital during the acute phase for at least 5 days and on day 5-8 were discharged with the lower home dose. On day 40-50, the treatment was stopped and the final follow-up visit was scheduled 5-7 months after trial enrollment.Endpoints The primary endpoint was the rate of death and new myocardial infarction during the first 6 days. Secondary endpoints were the rates of death and new MI after 40 and 150 days, the frequency of revascularization procedures and need for heparin infusion, and a composite endpoint. Cause of death and myocardial infarction were verified by the independent endpoint committee who had to differentiate a new event from an inclusion event. Safety endpoints included major and minor bleeding. Major bleeding was defined by a drop of ≥2 g/dL in hemoglobin with associated signs or symptoms of bleeding, and minor bleeding was any other bleeding not meeting the former criteria. A sample size of 1,500 was based on a power of 0.80 to detect a reduction in the primary composite endpoint from 6% to 3% at a 2-sided alpha of 5%. Subgroup analyses were prespecified and a “high-risk group” was defined by the presence of at least 2 of the following variables: age >70, previous MI, medically treated heart failure, or diabetes.Results 1,506 patients were included in the final analysis; 757 in the placebo group and 741 in the dalteparin group. At 6 days, dalteparin significantly reduced the occurrence of the primary endpoint (RR 0.37; 1.8% vs 4.8%; 95% CI 0.20-0.68), which was driven by myocardial infarction (RR 0.33; 1.4% vs 4.4%; 95% CI 0.16-0.60). There was no difference in death between groups (RR 0.88; 0.9% vs 1.1%; 95% CI 0.32-2.48) and minor bleeding events were much more common in the dalteparin group (8.2% vs 0.3%).At 40 (8.0% vs 10.7%) and 150 (14.0% vs 15.5%) days, differences between groups were less pronounced for the primary endpoint and the results, in favor of dalteparin, were not statistically significant. Bleeding events, driven by minor bleeding, continued to be much higher for the dalteparin group.Subgroup analyses are presented at 6 and 40 days and are generally concordant across subgroups, meaning the treatment effect goes in the same direction, but these analyses should be viewed skeptically as they represent small sample sizes, particularly compared to subgroups in the earlier mega trials. Subgroup data suggests concordant results for patients less than or greater than 70 years of age and for patients meeting high risk criterion compared to those not meeting it.Conclusions In patients with unstable angina and NSTEMI, dalteparin reduced the primary endpoint of death or nonfatal MI compared to placebo at 6 days and was associated with a NNT of 33 patients. This was driven by a reduction in nonfatal MI. The results were no longer significant at 40 or 150 days. This trial is limited by small sample size and highly selected patient population.Thank you for reading Cardiology Trial's Substack. This post is public so feel free to share it. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Our two guests, Dr. Greg Stefano Interventional Cardiologist and Geoffrey Patty, Chest Pain Coordinator, with the UH Harrington Heart and Vascular Institute, are still with us talking about patients experiencing out-of-hospital STEMI situations.  STEMIs can be confusing but, taking the assessment one step at a time and not being shy about activating a STEMI team is crucial.

Lancet 1992;339:753-770.Background Results from the GISSI and ISIS-2 trials demonstrated a clear benefit for the early opening of acutely blocked arteries with fibrinolytic treatment in patients presenting with STEMIs. ISIS-2 also demonstrated the benefit of aspirin in the acute and subacute phases of MI. However, after opening a blocked artery, concern for re-occlusion persisted, especially in the first several days to week, and experts postulated that antithrombotic therapy with heparin could improve outcomes compared to use of aspirin alone. The 3rd study from the ISIS group sought to test the hypothesis that therapeutic heparin plus aspirin reduced mortality compared to aspirin alone in patients treated with early fibrinolytic therapy. The investigators also sought to test whether different fibrinolytic regimens were safer and more effective compared to each other. *Since treatment with fibrinolytic therapy is no longer standard practice in most places and no significant differences in fibrinolytic regimens were ultimately reported, we will focus only on the heparin plus aspirin versus aspirin alone portion of the study.Patients Patients were eligible for ISIS 3 if they were thought to be within 24 hours of the onset of symptoms of suspected or definite acute MI (with or without ECG changes) and if they had no definite contraindications to fibrinolytic therapy. Contraindications were not specified by protocol but by the responsible physician; standard contraindications to fibrinolysis were suggested. Patients were eligible even if aspirin or heparin was thought to be clearly contraindicated or if it was thought that aspirin alone was not enough (i.e., that some anticoagulant was clearly indicated). In such cases, patients were still to be randomized and the allocated antithrombotic regimen was then modified as thought appropriate for the particular patient.Baseline characteristics The majority of patients were men (73%) and under the age of 70 years who presented within 6 hours from the onset of pain (78%). Enrolled patients appeared to be generally stable as only 6% had SBP

Pharmacist, Kevin Kaucher, joins us to discuss the ins and outs of nitro in acute coronary syndrome. Does it work? Is sublingual better than paste? Can it be dangerous? Come learn the latest on nitroglycerin.  For more info and to see the EKGs from the case: https://emspodcast.com/the-truth-about-nitro-separating-fact-from-fiction/  

We recognise that psychological safety, namely our ability to trust, communicate and create, is vital for enhanced team working and decision-making in the complex world of modern healthcare delivery. However, how we develop such a high-performing culture remains a challenge. In today's episode, we're going develop a deeper understanding of the role of simulation training, and the challenges and opportunities that exist in utilising this educational tool in improving psychological safety. FURTHER LEARNING If you're a member of Medical Protection join us for an upcoming Virtual Workshop: Beating Burnout https://protection.pub/3fipeuj Recommended sources by Dr Eve Purdy Establishing a Safe Container for Learning in Simulation https://journals.lww.com/simulationinhealthcare/fulltext/2014/12000/establishing_a_safe_container_for_learning_in.2.aspx The Culture Code https://danielcoyle.com/the-culture-code/ Timing, Tribes and STEMIs https://vimeo.com/418712820 CERTIFICATE A certificate of learning for listening is available on PRISM https://protection.pub/3WtX54j SPEAKERS Our host today was Dr Najeeb Rahman https://www.linkedin.com/in/najeeb-rahman-6634b42 Our guest speaker today was Dr Eve Purdy https://twitter.com/purdy_eve For more information about Medical Protection please visit www.medicalprotection.org

In this high yield episode, we review the clinical presentation, up front investigations, immediate and long-term management of patients who present with STEMIs - one of the 5 causes of life-threatening chest pain. Our medicine minute reviews the PLATO trial, which supports the use of ticagrelor over clopidogrel as the second agent in dual anti-platelet therapy in patients with ACS. Written by: Drs. Varun Srivatsav and William Kennedy (Internal Medicine Residents)Reviewed by: Dr. Jonathan Dean (GIM) and Dr. Andrea Lavoie (Cardiology)Sound Editing by: Nathan Doupnik (Medical Student)Infographic by: Drs. Varun Srivatsav and William Kennedy (Internal Medicine Residents)Infographic edited by: Vincent Li (Medical Student)This episode was supported by Spatula Foods. Enjoy elevated cuisine every day with high-quality dishes you can cook yourself in just 10 minutes. Go to https://www.spatulafoods.com and use promo code INTERN for $40 off your first box- this will help support our podcast! Support the show

This year we are very fortunate to have Dr. Amal Mattu, EKG Jedi, as teaching faculty for our 39th Maine Medical Center/Maine ACEP Winter Symposium. In this lecture, he helps us differentiate septal STEMIs from other potentially life threatening mimics. Click here for show notes To check out our virtual 39th Winter Symposium, check out the conference website at www.mmcwintersymposium.com     Jeff Holmes, MD

This week features two Feature Discussions. In our first feature discussion, Nikkil Sudharsanan and Associate Editor Ntobeko Ntusi as they discuss the article "Variation in the Proportion of Adults in Need of BP-Lowering Medications by Hypertension Care Guideline in Low- and Middle-Income Countries: A Cross-Sectional Study of 1,037,215 Individuals from 50 Nationally Representative Surveys." Then in our second feature discussion, join author Aloke Finn and Associate Editor Jeffrey Saffitz as they discuss the article "Microthrombi As A Major Cause of Cardiac Injury in COVID-19: A Pathologic Study." One addendum to the Feature Discussion with Drs. Sudharsanan and Ntusi: ·       Dr. Sudharsanan wanted to clarify that treatment needs were determined for each country based on multiple blood pressure measurements taken on the day of the survey; however, all the estimates were based on BP measured on just one day, rather than over several weeks as is done in clinical practice. This is related the final question posed in the first Feature Discussion. TRANSCRIPT BELOW 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 Greg Hundley Associate Editor for the Pauley Heart Center in Richmond, Virginia at VCU Health. Dr. Carolyn Lam: Guess what, Greg, it's another issue with a double feature. We are going to be discussing microthrombi as a major cause of cardiac injury in COVID-19. Dr. Greg Hundley: Yes, Carolyn and our second discussion will be centered on blood pressure lowering in low and middle-income countries. But how about you and I both grab a cup of coffee and jump into the other articles in this issue. Dr. Carolyn Lam: Sure thing. I got my coffee and let's start with gestational diabetes. Now, we know that leads to an earlier onset and heightened risk of type 2 diabetes, which is a strong risk factor for cardiovascular disease. But Greg, do you think that attaining normal glycemia following gestational diabetes can ameliorate the access risk? Dr. Greg Hundley: Carolyn, that's a really great question. I would think so but how about you tell me what these authors found. Dr. Carolyn Lam: Yep. This next paper it's from Dr. Gunderson from Kaiser Permanente, North California and colleagues. They exactly sought to answer the question and realize that it was unclear whether attaining normal glycemia can ameliorate the excess cardiovascular disease risk that's associated with gestational diabetes. So they evaluated gestational diabetes history and glucose tolerance after pregnancy and found out whether or not it was associated with coronary artery calcification in women. The obtained data from the CARDIA study which is a US multicenter community-based perspective cord of young black and white adults age 18 to 30 years at baseline. Dr. Carolyn Lam: This is what they found. Women without previous gestational diabetes showed a greater increase in the risk of coronary artery calcification associated with worsening glucose tolerance. However, women with a history of gestational diabetes had a twofold higher risk of coronary artery calcification across all subsequent levels of glucose tolerance. Midlife atherosclerotic cardiovascular disease risk among women with previous gestational diabetes is therefore not diminished by attaining normal glycemia. And this is discussed in an accompanying editorial by Dr. Jennifer Green from DCRI entitled Cardiovascular Consequences of Gestational Diabetes. Dr. Greg Hundley: Carolyn, well, sounds like I was wrong but our next paper, it's going to review for us a little bit about IgE. Remember that immunoglobulin associated with itching. So Carolyn immunoglobulin E or IgE belongs to a class of immunoglobulins involved in immune response to specific allergens. However, the roles of IgE and IgE receptor in pathological cardiac remodeling and heart failure or a non. So in this study, the investigative team measured serum IgE levels and cardiac IgE receptor expression in diseased hearts from humans and mice. Dr. Carolyn Lam: Oh, Greg, I'm itching to find out what this study showed. Dr. Greg Hundley: Yes, Carolyn, going from the quizmaster now to is it comedy now? Serum IgE levels were significantly elevated in patients with heart failure as well as in two mouse cardiac disease models induced by chronic pressure overload via transverse aortic constriction and chronic angiotensin two infusion. Now, interestingly Carolyn, IgE receptor expression levels were also significantly up-regulated and failing hearts from human and the mouse model. Dr. Greg Hundley: Carolyn, the authors found that IgE induction plays a causative role in pathological cardiac remodeling at least partially via the activation of IgE receptor signaling in cardiac myocytes and cardiac fibroblasts. So future studies are needed to determine if therapeutic strategies targeting the IgE receptor axis and as to whether they may be effective for managing IgE mediated cardiac remodeling. Dr. Carolyn Lam: Fascinating. I never thought of IgE involved in cardiac remodeling. Now, this next paper really interesting. Regulators are always evaluating the use of non-interventional real-world evidence studies to assess the effectiveness of medical products. The RCT DUPLICATE Initiative was formed to use a structured process to design real-world evidence studies to emulate randomized control trials and compare results. Now, this paper represents the first 10 trials emulations in RCT DUPLICATE, and it's from Dr. Jessica Franklin from Brigham and Women's Hospital and Harvard Medical School in Boston and her colleagues. And they did this to evaluate cardiovascular outcomes of antidiabetic and antiplatelet medications. Dr. Greg Hundley: Wow, Carolyn. So how does they do this? Dr. Carolyn Lam: So they use patient level claims data from US Commercial and Medicare-PEERS and implemented inclusion exclusion criteria of the trial selected primary endpoints and compare the populations to emulate those of each of the corresponding randomized controlled trials within the trial mimicking populations, they then conducted propensity score matching to control for more than 120 pre-exposure con founders. Dr. Greg Hundley: So Carolyn, were they able to emulate their randomized clinical trial results? Dr. Carolyn Lam: Now, despite the attempts to emulate the trial design as close as possible, there were still differences between the randomized control trial and the corresponding real-world evidence study population. The regulatory conclusions were equivalent in six of 10 studies. The real-world evidence emulations achieved a hazards ratio estimate that was within the 95% confidence interval from the corresponding trial in 8 of 10 studies. Agreement between the trial and real-world evidence findings varied depending on which agreement metric was used. Dr. Carolyn Lam: Interim findings indicated that selection of active comparative therapies with similar indications and use patterns enhance the validity of the real-world evidence. And so, even in the context of active comparators concordance between trial and real-world evidence findings was not guaranteed partially because trials were not emulated exactly. More trial emulations are needed to understand how often and in what context real-world evidence findings will match the trials. And yet these initial findings of RCT DUPLICATE really indicate circumstances when real-world evidence may offer causal insights where trial data is either not available or cannot be quickly or feasibly generated Dr. Greg Hundley: Well, Carolyn, that is really interesting findings there because we're all trying to decide what to do with these large data sets and combining the results of millions and millions of data points and very interesting findings in this study. How about we see what else is in the issue? Dr. Carolyn Lam: Absolutely. Well, let me start. There's an exchange of letters among doctors Villarreal, Cárdenas Suri, [and] Navarro-Castellanos regarding the Multi-system inflammatory syndrome in children. The ECMO needs and Kawasaki disease likeness. There's also an ECG challenge by Dr. Pillai entitled "A Tale of Two Blocks". Dr. Greg Hundley: Well, Carolyn, I've got a very nice In-Depth review from Dr. Van Belle regarding transcatheter aortic valve replacement in bicuspid aortic valve stenosis. And there's a Research Letter from Dr. Lew entitled “Short-Chain Enoyl-CoA Hydratase Mediates Histone Crotonylation and Contributes to Cardiac Homeostasis.” And then finally, Dr. Nordin Hanson from Amsterdam has a very nice piece on the Clinical Implications of Basic Science Research entitled “DAMPening Mortality in COVID19: Therapeutic Insights from Basic Cardiometabolic Studies on S100A8/A9.” Well, Carolyn, how about we check out the double feature. Dr. Carolyn Lam: Definitely let's go, Greg. Dr. Greg Hundley: Well listeners, we are here for our first feature discussion on this March 9th issue and we have with us Nikkil Sudharsanan from Heidelberg and also our own Associate Editor Ntobeko Ntusi from Cape Town. Welcome gentlemen. Nikkil, could you please describe for us the hypothesis that you wanted to test your study population and your study design? Dr. Nikkil Sudharsanan: Yeah, so for our hypothesis, we really wanted to know, depending on which hypertension treatment guideline you chose, what implications does it have at the population level for the number of people in low and middle-income countries that would require treatment or that you would want to place on treatment. And we were really looking at not just one country, but a whole range of 50 low and middle-income countries. And so our study population is actually from this pretty remarkable data source that combines the World Health Organization surveillance data for many countries with other sources of data, to try to create a comparable almost low and middle-income country super dataset that's specifically designed to answer questions around cardiovascular disease. So our study population was really based on population representative samples for each of the 50 countries we considered. And in most of the countries we focused on the adult population. So those ages 30 and above. Dr. Greg Hundley: And your total sample was over a million participants, correct? Dr. Nikkil Sudharsanan: Yeah, it's a really huge sample. And I think it's a testing to some of these data sources, especially the ones in India and Brazil, but collected just really large sample sizes that contributed to this huge global population. Dr. Greg Hundley: Very nice Nikkil. And what did you find? Dr. Nikkil Sudharsanan: So the big finding is we actually went into it not knowing how the choice or how strong the choice of a blood pressure treatment guideline would be on the number of people that required treatment and were really surprised to see that we took more treatment guidelines, the 2018 American College of Cardiology, American Heart Association guidelines, the kind of typical 140 by 90 blood systolic diastolic blood pressure threshold that you see as part of a lot of guidelines. The UKs NICE guideline and then the WHO Hearts guideline, which is based on their pen and package of essential non-communicable disease interventions. Dr. Nikkil Sudharsanan: And we started a really, really pronounced difference in the proportion and size of the adult population that you would recommend or place under hypertension treatment, depending on which of these guidelines used to decide who gets treatment across these countries. So at the top, we found the American College of Cardiology, American Heart Association guidelines, and for the countries we were considering it put about 27% of women and a really high 35% of men as recommended for blood pressure treatment. Dr. Nikkil Sudharsanan: And then very closely followed to that was the 140, 90 threshold. So it was still high, but not as high, I would think it was around 26% of women and 31%. And then between these two guidelines and the UK NICE and WHO Hearts, there was a really big drop-off in how many people would actually be recommended for blood pressure treatment. Dr. Nikkil Sudharsanan: The NICE guideline, for example, only have 12% of women and about 16% of men and the WHO Hearts is by far the lowest, which only about 10% of women and 11% of men. So I think our first really striking finding was that this choice is not trivial. And depending on which guideline you actually choose to decide who gets treatment in that country, it has really big implications for how many people in that country are going to need treatment. Dr. Greg Hundley: Very good. And Ntobeko, how do you put the results of this study in the context with other research perform to study hypertension? Dr. Ntobeko Ntusi: Thank you, Greg. So we know that although more than 80% of the global battle of Cardiovascular Disease, okay. As in low and middle-income countries, the data around respecters for cardiovascular disease has largely come from high-income countries. And the INTERHEART study was really the first publication about 15 years ago to try and address this question. And it was very apparent both in the INTERHEART study as well as the INTERHEART Africa study of hypertension was one of the key respecters not only for my myocardial infraction, but for cardiovascular disease in general. Dr. Ntobeko Ntusi: In the INTERHEART study hypertension having a hazard ratio of two and the population attributable risk of 17%. And then the INTERHEART Africa study having a hazard ratio of over six. And this paper is really an important application in my view, showing that in a comparison of over a million individuals from 50 countries, there is great variation in the proportion of individuals that need to be treated for hypertension, based on the choice of guideline and definition of hypertension. And if you look at figure one, this is variable from anywhere from 9% to 35%. Dr. Ntobeko Ntusi: The other important contribution of this paper is that the proportion of the population that needs to be treated for hypertension increases with age, which is something that we know but strikingly more than 60% in those over the age of 60 years. And for me, they are really great core key messages that I think are important contributions from this publication. The first one being that the choice of hypertension treatment guideline significantly influences the denominator of what you consider to be hypertensives in your population. The second one is that many people in low and middle-income countries are still unaware of their status of elevated blood pressure and the need for treatment. And I think this is a key point to emphasize. Dr. Ntobeko Ntusi: The third important message is that these first two points I've made have got huge implications for the scale-up costs and healthcare system capacity and that countries need to choose definitions for diseases. And this needs to be aligned with national health policy as well as available resources. And then finally, a key part of the discussion, which I asked the author to address was really around our understanding of the barriers to optimal management of blood pressure in low and middle-income countries and how these gaps can be oppressed. And they speak to the economic and human resources, the health policy, the importance of population screening and importantly education at every level. Dr. Greg Hundley: Very good. Nikkil I'd like to come back to you and then maybe 20 seconds or so, what do you think is the next study that needs to be performed really in this area of research? Dr. Nikkil Sudharsanan: I think there may be two, one is to really build on this in terms of what we showed this is the proportion of people that would require treatment and that's how it varies across these guidelines. I think it's important to also tie that to the resource implications directly, like Dr.Ntusi said, to actually show this guideline would require this many resources versus this many for that guideline. I think that will really help countries in deciding what's actually feasible guideline to implement. Dr. Nikkil Sudharsanan: And the second one, which is I think a much more challenging study to do is just a study of all these guidelines are based on mostly data from high-income countries. And even among these high income countries, there's these discussions on what the appropriate level for treatment is and what point you should initiate treatment. And it seems like this really has not been done with low and middle-income country populations. So we're arguing about four different guidelines that were built for high-income country populations. And I think it would be really important to see some sort of trial or long-term observational study actually in terms of averting cardiovascular disease events which guidelines actually makes the most sense for these countries. Dr. Greg Hundley: Very good. Ntobeko, anything to add to that? Dr. Ntobeko Ntusi: I think I agree completely with Nkkil and I think this paper has a number of really important strengths, and I think those strengths and key contributions have to be taken in the context of one significant limitation and how we interpret these results. And that's the fact that when we normally see a patient in the clinic to diagnose hypertension, we would take two or three blood pressure measurements. In this study, they only took a single blood pressure measurement and that's the basis for the conclusions and for me a key limitation, but nonetheless, I think a very important contribution. Dr. Greg Hundley: Very nice. Well listeners, we want to thank Nikkil Sudharsanan from Heidelberg and Ntobeko Ntusi from Cape town for bringing us this important study, indicating that worldwide there's substantial variation really in the proportion of adults in need a blood pressure lowering medication, depending on which hypertension guideline is used. Well, let's move on now to our second feature discussion.   Dr. Greg Hundley: Listeners, we are now to our second feature discussion and we have with us Dr. Aloke Finn from the Cardiovascular Path Institute in Gaithersburg, Maryland and our content editor expert for pathology, Dr. Jeff Saffitz from Beth Israel Deaconess. Welcome gentlemen. Aloke, could you describe for us, what was the question you wanted to address with this researching? What was your study design and your study population? Dr. Aloke Finn: Great. Greg, thanks for your interest in our article and for highlighting it. We were really interested in understanding what the pathologic causes for cardiac injury were in people hospitalized with COVID-19, as you know, it's been reported in the literature that people with COVID-19 with cardiac injury do worse than those without cardiac injury, but the mechanism is not still well understood. So the study design was really based upon a collaboration with a group from Italy in the Lombardy region, where they had had a terrible outbreak in 2020, as you remember in February. And they had a number of hospitalized. People die from COVID-19 infection, and they too were interested in understanding the pathologic causes of chronic injury. We got IRB approval and those hearts were sent to us during the middle of this pandemic in the February, March time. And we were able to examine 40 of those hearts and report our pathologic findings. And these were unselected cases of hospitalized patients dying of COVID-19. Dr. Greg Hundley: That was great. And tell us a little bit what were your study results? Dr. Aloke Finn: So we, first of all, did an analysis based upon the presence of myocardial necrosis. So that was the sort of the selection factor, which hearts had myocardial necrosis which parts didn't have myocardial necrosis. We found that 35% of the hearts in this 40 cases had myocardial necrosis. Now, we divided those into the type or pattern of myocardial necrosis. Was it acute myocardial infarction? Was there a large area of infarction greater than one centimeter squared or was there focal myocardial necrosis less than one centimeter squared. It's small areas of focal myocardial necrosis. We've found that most cases of patients dying of COVID-19 with myocardial necrosis had focal myocyte necrosis. Not large areas but small areas of myocyte necrosis. And we looked for the cause of those necrosis, majority of those cases with focal myocyte necrosis had microthrombi as the cause of that necrosis. So that suggests the major mechanism of myocardial injury in COVID-19 patients is microthrombi. Dr. Greg Hundley: Very nice. Well, Jeff, let's turn to you. How do we put the results of this study in the context with perhaps other pathologic studies that have been obtained from hearts of individuals that succumb to COVID-19? Dr. Jeffrey Saffitz: It's a very important question. And I want to say that at the outset, there have been many papers published focused on the pathologic findings of COVID-19 patients who have come to autopsy. And I have to say that the quality of these papers has been quite variable. In many cases, the pathology being shown is actually post-mortem artifact. In other cases, the interpretation of the pathology is incorrect. And so I think we have to be very careful in a study like this to make sure that what is being reported is actually valid and meaningful in the context of the important clinical questions being posed. And in this case, I can say the pathology was really extremely impressive and very convincing. Dr. Jeffrey Saffitz: Another important aspect of this study has to do with the comparison of the composition of the microthrombi that were identified in patients dying from COVID-19 versus patients who have other types of coronary thrombosis, but in a different setting. And here, there were some interesting observations that provide insights, not only into mechanism of thrombosis, but also potential information about how one might want to target antithrombotic therapy in these patients. So I would really like to hear more from Dr. Finn on this interesting aspect of this study. Dr. Aloke Finn: Jeff, thanks for your comment and your question. I think I agree with you, this was another interesting aspect of the study. What was done was that were able to examine the constituents of thrombi, different types of thrombi both in the setting of patients who had COVID-19 and non COVID-19 STEMIs as well as microvascular thrombi described in the COVID-19 patients, as well as embolized thrombi that embolized a small microvascular within the heart. And what we essentially found was that these thrombi, that are COVID microthrombi are distinct in their constituents. Distinct in that they had more fibrin and more compliment activation than the other types of thrombi that we're studied. So I do think this begins to unravel the question about how are these thrombi forming and are they different from the type of thrombi we normally treat? And the answer is, yes. Dr. Greg Hundley: Very nice, Aloke. What study do you think needs to be performed next in this space? And after you, I'll ask Jeff the same question. Dr. Aloke Finn: Greg, I would like to know whether or not therapies like anticoagulant, anti-compliment, antiplatelet therapies can decrease the risk or the effect of the COVID-19 on myocardial injury. Is will we see a benefit to anticoagulant or antithrombotic strategies in the study? I think that is the natural next question to ask. Dr. Greg Hundley: Very nice. And Jeff, anything to add? Dr. Jeffrey Saffitz: Yeah, well, I'm an experimental pathologist, so I'm always interested in disease mechanisms. And I would like to understand more about how these microthrombi form, the role of endothelial cell injury, the role of cytokine storm and other factors which we know are contributing. I think in the end having a more fundamental understanding of these mechanisms will provide important insights, not only in trying to manage heart disease, but in fact, other organ system disease, which is likely being mediated by a similar mechanism in the kidney and potentially in the brain and other organs as well. So I think this is a great example about how autopsy can provide really critically important information in a new human disease and set the stage for subsequent studies that will really provide important dew information. Dr. Greg Hundley: Excellent. Well listeners, we want to thank Dr. Aloke Finn from Gaithersburg, Maryland, Dr. Jeff Savitz from Boston, Massachusetts for this excellent discussion and revealing the pathologic results of 40 hospitalized patients from Italy that expired after COVID-19 highlighting the cause of myocardial necrosis and how it was related to the presence of microthrombi. Dr. Greg Hundley: 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.  

Let’s talk about tribes. Some could say that healthcare is a bit like a tribal jungle. The multiple professions, specialties, departments, tribal language, tribal dress.  On one hand, feeling like you belong to a tribe is fulfilling and encouraging.  But, there is a dark side to tribalism and some of Vic Brazil's toughest days at work is when this dark side comes out.  For more head to: codachange.org/podcasts

Contributor: Jared Scott, MD Educational Pearls: EKGs look at different angles, or vectors, of the heart’s electrical conduction as it travels through the heart. Knowing how to read these vectors is essential in diagnosing locations of cardiac pathologies  Leads II, III, and aVF follow an inferior path, so ST elevation in those leads indicates inferior involvement Major complications more common with inferior STEMIs can include:  hypotension which can be made worse by nitroglycerin Severe bradycardia due to SA/AV node involvement Inferior STEMI, barring no hypotension or bradycardia, have better mortality than other types  References Warner MJ, Tivakaran VS. Inferior Myocardial Infarction. 2020 Aug 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan–. PMID: 29262146. Summarized by Jackson Roos, MS4 | Edited by Erik Verzemnieks, MD The Emergency Medical Minute is excited to announce that we are now offering AMA PRA Category 1 credits™ via online course modules. To access these and for more information, visit our website at www.emergencymedicalminute.com/cme-courses/ and create an account. 

On today's episode we discuss: —Epidemiology: A meta-analysis of 15 peer-reviewed articles found recurrent COVID-19 infections (confirmed via RT-PCR) were reported at a mean of 34 ± 10.5 days after full clinical recovery from an initial infection, but these patients also had persistent positive RT-PCR tests for a mean of 39 ± 9 days following their initial infection. Furthermore, a persistent positive test could be detected in patients without clinical relapse for 54 ± 24 days following initial infection. —Understanding the Pathology: Investigators describe post-mortem neuropathological findings in 2 patients with COVID-19 and neurological decompensation. Case 1 showed widespread multi-focal cortical infarcts, and case 2 showed brainstem encephalitis. Since viral RNA was not detected in the post mortem brain tissue in either case, these pathologies may not be a direct consequence of viral invasion. —Transmission & Prevention: Researchers argue that hurricane protection measures, such as evacuation and sheltering, cause people to gather together and is the paramount reason for the 3.7x increase in COVID-19 cases between May 1 and July 24, 2020. They suggest that during hurricanes, 1) people at risk should social distance, 2) officials should provide better communications for guidance on safe evacuation and sheltering, and that 3) we should "learn from each 2020 storm and refine operations." —Adjusting Practice During COVID-19: Pharmacists and epidemiologists in Denmark conducted a population-based cohort study of 9,236 patients who tested positive for SARS-CoV-2 via PCR and found no significant difference between NSAID users (n=248) and non-NSAID users (n=8,988) regarding 30-day mortality, hospitalization, ICU admission, mechanical ventilation, or renal replacement therapy. Authors suggest NSAID use during COVID-19 infection may have minimal effect on risk of mortality or adverse outcomes. · A survey of 414 interventional cardiologists and cardiac catheterization laboratory (CCL) directors in the United States found a 55% decrease in percutaneous coronary interventions (PCI) and a 64% decrease in transcatheter aortic valve replacements during March 15 to April 15, 2020 compared to 2019. Additionally, procedure deferral for angiogram/PCI for unstable angina, NSTEMI, and STEMI increased with greater inpatient COVID-19 burden and 40% of CCL directors reported increased cases of late presenting STEMIs. These findings suggest that patient fears due to the pandemic may be influencing their decisions to delay seeking urgent cardiac care. —R&D: Diagnosis & Treatments: Editors from the New England Journal of Medicine had an audio discussion to discuss guidelines for deployment of a COVID-19 vaccine. --- Support this podcast: https://anchor.fm/covid19lst/support

COVID-19 causes STEMI’s, arrhythmias and myocarditis?!? Emergency medicine and cardiology guru Amal Mattu, MD chats with Mizuho Morrison, DO on the cardiovascular effects of COVID-19. They discuss: the known pathophysiology of how viral infections affect the heart; Review the new consensus statement from the Society of Cardiovascular Angiography and interventions (SCAI), American College of Cardiology (ACC), and the American College of Emergency Physicians (ACEP) on how to manage STEMIs; and lastly discuss how cardiac arrest management differs in this COVID era.    To view the references and show notes from this podcast Click here

COVID-19 causes STEMI’s, arrhythmias and myocarditis?!? Emergency medicine and cardiology guru Amal Mattu, MD chats with Mizuho Morrison, DO on the cardiovascular effects of COVID-19. They discuss: the known pathophysiology of how viral infections affect the heart; Review the new consensus statement from the Society of Cardiovascular Angiography and interventions (SCAI), American College of Cardiology (ACC), and the American College of Emergency Physicians (ACEP) on how to manage STEMIs; and lastly discuss how cardiac arrest management differs in this COVID era.    To view the references and show notes from this podcast Click here

COVID-19 causes STEMI’s, arrhythmias and myocarditis?!? Emergency medicine and cardiology guru Amal Mattu, MD chats with Mizuho Morrison, DO on the cardiovascular effects of COVID-19. They discuss: the known pathophysiology of how viral infections affect the heart; Review the new consensus statement from the Society of Cardiovascular Angiography and interventions (SCAI), American College of Cardiology (ACC), and the American College of Emergency Physicians (ACEP) on how to manage STEMIs; and lastly discuss how cardiac arrest management differs in this COVID era.    To view the references and show notes from this podcast Click here

COVID-19 causes STEMI’s, arrhythmias and myocarditis?!? Emergency medicine and cardiology guru Amal Mattu, MD chats with Mizuho Morrison, DO on the cardiovascular effects of COVID-19. They discuss: the known pathophysiology of how viral infections affect the heart; Review the new consensus statement from the Society of Cardiovascular Angiography and interventions (SCAI), American College of Cardiology (ACC), and the American College of Emergency Physicians (ACEP) on how to manage STEMIs; and lastly discuss how cardiac arrest management differs in this COVID era.      Promo code for 3 month trial of ERcast in intro segment Hippo education COVID resource site: Link   References:  Mahjid, M. Payam, S. et al. Potential Effects of Coronaviruses on the Cardiovascular System: A Review [published online ahead of print, 2020 Mar 27]. JAMA Cardiol. PMID 32219363 Mahmud E, Dauerman HL, et al.  Management of Acute Myocardial Infarction During the COVID-19 Pandemic,CONSENSUS STATEMENT from the Society of cardiovascular angiography and interventions (SCAI), American College of Cardiology (ACC), and the American College of Emergency Physicians (ACEP). Journal of the American College of Cardiology (2020), doi https://doi.org/10.1016/j.jacc.2020.04.039. PMID:32330544 Edelson D, Sasson C. et al. Interim Guidance for Basic and Advanced Life support in Adults, Children and Neonates with suspected or confirmed COVID-19. Circulation AHA April 2020. PMID: 32270695 Stefanini GG, Azzolini E, et al. Critical Organizational Issues for Cardiologists in the COVID-19 Outbreak: A Frontline Experience From Milan, Italy [published online ahead of print, 2020 Mar 24]. Circulation 2020. PMID: 32207994

Perseverance, or more simply stated, Grit, is a common trait amongst EMS providers.  It grants us the ability to endure in the face of hardship when others may consider quitting or failing.  In regards to COVID 19, we are all playing the long game, it is a marathon (unfortunately) rather than a sprint.  We must stay united as a group and stay true to our mission of supporting and protecting our communities despite the pandemic.  That is not to say that we are not human ourselves.  While perseverance is one of the characteristics I value most in EMS providers, another virtue I’d care to juxtapose it to is vulnerability. In any situation that presents a threat — be it physical or emotional — our natural instinct is to protect ourselves. That's just basic survival. We try to defend, hide or deny our own insecurities and weaknesses. Being vulnerable involves letting yourself feel all things — the good, the bad and the not-so-pretty — and then also letting someone else see it all. Trying to be invulnerable can be exhausting, as much as we’d like to be super heroes protecting the population from medical maladies we must also acknowledge our own humanity.  This is not easy and it’s okay to express that and seek support.  When we numb feelings like fear, embarrassment and pain, we also numb excitement, hope, gratitude and happiness. Allowing vulnerability into our lives can rejuvenate our senses and actually foster, build and restore our community and make us more connected. I’m including the link to Brene Brown’s TED talk on vulnerability that has nearly 50 million views. Thank you all again for always being in service and a very happy EMS Week.   https://www.ted.com/talks/brene_brown_the_power_of_vulnerability   Today’s episode brings us 2 EMS physicians from Stanford on the topic, “Where have all the STEMIs gone?” where we dive into the literature and statistics on cardiac arrest, dying at home, emergency department volume and numerous other items related to COVID19. Interestingly both domestically and abroad there has been a dramatic reduction in heart attacks, strokes and traumas that have been presenting via EMS to the ED.  We discuss potential hypotheses into this phenomenon and also explore other salient details related to COVID.    Bryan David Sloane, MD – Is the current EMS fellow at Stanford University.  He did his residency at Harbor UCLA where he lived out his EMERGENCY! Dreams.  He was an EMT in LA for 6 years before medical school and considers himself an EMT first and a physician second.  He hopes to take an attending position at Kaiser South Sacramento where he will also be working on many local EMS initiatives.   Gregory H. Gilbert, MD - Clinical associate Professor of Emergency Medicine at Stanford University. Medical Director of San Mateo County and EMS Fellowship Director at Stanford University. He grew up in New York State and received his MD, from SUNY Downstate with distinction for investigative scholarship. He completed his emergency medicine training in Atlanta, Georgia at Emory University and is dual boarded in EM and EMS.  Please leave us your thoughts and comments, we'd love to dig further into this topic.  Make sure to leave @EMS_Nation a 5 star review wherever you listen to podcasts and to share the episode with friends and colleagues to pass along this #FOAMed resource.  Checkout the blog at EMSNation.org and say hello to Dr. Faizan H. Arshad on Twitter and Instagram @emscritcare. Wishing everyone a safe tour and a "happy" EMS Week!     

We interrupt our normal FOAMcast episodes to bring you updates from COVID-19, as literature develops. *Things change frequently and this may be out of date in days/weeks. So, check back for updates/fact check what you hear* This episode is a literature potpourri  Outcomes in pregnancy (Knight et al - pre-print). Are EMS calls for strokes and STEMIs down during the pandemic? Holmes et al More pediatric hyperinflammatory /Kawasaki-esque cases from Italy Verdoni et al More Kawasaki Disease in Paris. (Toubiana et al) Aerosol boxes for intubation (Begley et al) Genomic sequencing reveals healthcare associated clusters (Meredith et al) Show notes: FOAMcast.org Thanks for listening, Lauren Westafer and Jeremy Faust *Recorded May 15, 2020

In our inaugural episode we discuss the importance of STEMI recognition, how STEMIs are QA'd by the county and what metrics are tracked. We also take a look at common 12-lead mistakes and those things that can mimic a STEMI on a 12-lead.  

Dr. Berberian joins EMRA*Cast with Alex Kaminsky to delve deeper into the pathophysiology and electrical findings associated with diagnoses such as WPW, Brugada and ARVD in part 1 of this series. Lumps and Bumps: Can’t-Miss Diagnoses in Syncope (Part 1) Host: Alex Kaminsky Guest: Jeremy Berberian, MD Associate Director of Resident Education: Christiana Health System Editor-in-chief: EMRA EKG Guide Author EM Resident Monthly ECG Challenge. Overview: Residents are well programmed to recognize cardiovascular emergencies such as STEMIs at a glance. However, during a busy shift it can be easy to overlook dysrhythmias and other electrophysiologic urgencies and emergencies. Syncope is a prime example of a chief complaint that may be uncovered with an EKG alone -- however syncopal emergencies are often subtle and nuanced. Dr. Berberian joins EMRA*Cast with Alex Kaminsky to delve deeper into the pathophysiology and electrical findings associated with diagnoses such as WPW, Brugada and ARVD in part 1 of this series. Key Points: Wolff-Parkinson-White (WPW) Prevalence: 0.7 to 1.7 per 10000 Overview: Accessory Pathway Connecting the atria to the ventricle. In some instances, this can cause the accessory pathway to travel FASTER than through the AV node. Orthodromic (Narrow): Travels down the AV node (can bypass) Antidromic (Wide): Bypasses AV node and UP the his-purkinje system.   Courtesy of CardioNetworks: Free use image Key Features:  Image: Courtesy of EMRA EKG Guide Short PR (less than 120ms) “Delta” wave -- which is a “slurring” of the QRS complex QRS might be “a little” wide (still 2mm with a negatively deflected T in right precordial leads (V1-V3) Potentially diagnostic as isolated EKG finding. Type 2: ST elevation in right precordial leads (V1-V3) with a “saddleback.” Within the STE.   Not completely diagnostic but concerning fr workup.   Clinical Criteria (EKG Findings PLUS one or more): SYNCOPE Nocturnal Agonal Respirations Brugada gets WORSE with parasympathetic stimuli. Family member with known Type 1 Observed/Documented VT/VF Sudden cardiac death in family member 55ms (in 95% of patients) Slightly prolonged QRS >110ms (Right precordial leads) VT looks more like a Left-bundle morphology -- Appreciate that AFTER the patient is out of VT.   Key Resources: *If needed and/or different than references* EMRA EKG Guide Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department with Syncope: Huff J.S., Decker W.W., Quinn J.V., Perron A.D., Napoli A.M., Peeters S., Jagoda A.S.( 2007)  Annals of Emergency Medicine,  49 (4) , pp. 431-444. Epidemiological profile of Wolff-Parkinson-White syndrome in a general population younger than 50 years of age in an era of radiofrequency catheter ablation. Lu C.-W., Wu M.-H., Chen H.-C., Kao F.-Y., Huang S.-K. (2014)  International Journal of Cardiology,  174  (3) , pp. 530-534. Reference, G. (2019). Brugada syndrome. [online] Genetics Home Reference. Available at: https://ghr.nlm.nih.gov/condition/brugada-syndrome#statistics [Accessed 14 Feb. 2019]. McNally E, MacLeod H, Dellefave-Castillo L. Arrhythmogenic Right Ventricular Cardiomyopathy. 2005 Apr 18 [Updated 2017 May 25]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1131/

There is only one corner of the universe you can be certain of improving, and that’s your own self. –Aldous Huxley Welcome back to RoshCast for Episode 45! Let’s start out with a review of rabies before getting to core content Q&A. The most common wild reservoirs of rabies are raccoons, skunks, bats, foxes, and read more... The post Podcast Ep 45: ARDS, Dental Fractures, STEMIs, Pericarditis, & More appeared first on RoshReview.com.

Show Notes Disclaimer: This is the unedited transcript of the podcast. Please excuse any typos. Jeff:  Welcome back to Emplify, the podcast corollary to EB Medicine’s Emergency Medicine Practice. I’m Jeff Nusbaum, and I’m back with my co-host, Nachi Gupta and we’ll be taking you through the August 2018 issue of Emergency Medicine Practice. Nachi: This month’s topic is one that Jeff has significant personal experience with from his college days. We’re reviewing Cannabinoids -- and emerging evidence in their use and abuse. Jeff: Um… that is definitely not true. I was actually a varsity rower in college... Are we still reviewing talking points together before we start recording these episodes? Nachi: Sometimes… Jeff: This month’s issue was authored by Mollie Williams, who is the EM residency program director at the Brooklyn Hospital Center. It was peer-reviewed by Joseph Habboushe, assistant professor at NYU and Nadia Maria Shaukat, director of the emergency and critical care ultrasound at Coney Island Hospital in Brooklyn, New York. Nachi: We’re going to be talking about the pathophysiology of cannabinoids, clinical findings in abuse, best practice management, differences between natural and synthetic cannabinoids, and treatment for cannabinoid hyperemesis syndrome. So buckle up and get ready. Jeff: As you’re listening through this episode, remember that the means that we are about to answer one of the CME questions from the end of the print issue. If you’re not driving while listening, be sure to jot down these answers and get your CME credit when we’re going through this issue.. Nachi: As of June 2018, there are 31 states, the District of Columbia, and 2 US territories that possess state and local-level laws allowing the use of cannabis medicinally or in recreational formulations. Marijuana actually maintains the highest lifetime use of an illicit drug used within the US. Jeff: There are a shocking 22 million past-month users of marijuana in the US, followed by pain relievers at 3.8 million, and cocaine at 1.9 million. Clearly, an important topic worth discussion, especially as synthetic products have become more widely available. Nachi: And worth noting -- Colorado, where medicinal and recreational marijuana use has been decriminalized and later legalized, has shown a nearly 2-fold increase in the prevalence of ED visits, which may be related to marijuana exposure. Jeff: Medicinally, cannabinoids are currently used in the treatment of chronic pain syndromes, complications of multiple sclerosis and paraplegia, weight loss due to appetite suppression in HIV/aids, chemotherapy-induced nausea and vomiting, seizures, and many other neuropsychiatric disorders. In fact, cannabis use has been documented for medical use dating as far back as 600 BC in West and Central Asia. Nachi: All of that being said though, there is an absence of high-quality reviews and evidence to support the use of cannabinoids for any of the indications you just mentioned. And the US DEA maintains cannabis as a Schedule I substance. Jeff: This DEA designation limits the ability to do research and obtain federal funding for such research. General lack of federal regulations on chemical content also leads to product variation, which may be a cause of increased incidences of accidental overdoses. Nachi: To attain the most up to date information for this article, Dr. Williams searched the PubMed and Cochrane Databases from 1950 to 2018. This produced predominantly case reports and retrospective studies. There were just a few randomized prospective studies -- not surprising. Jeff: Let’s get started with the pathophysiology. There are 3 cannabis species to be aware of: Cannabis sativa, cannabis indica, and cannabis ruderalis. Within these species, over 545 active cannabis-derived components have been described. Nachi: There are ten main constituents of cannabis sativa. Of these, 9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD) are found in the greatest quantities. The neuropsychiatric and addictive properties of cannabis are due primarily to the delta-9-THC. Jeff: THC and other cannabis derivatives work through the endocannabinoid system and other neuroregulators. The endogenous cannabinoid system has 4 components: (1) endogenous endocannabinoids, (2) receptors, (3) degradation enzymes, and (4) transport mechanisms. Nachi: There are two endogenous endocannabinoids to know about: anandamide (AEA) and 2-arachidonoyl-glycerol. Jeff: Cannabinoid receptors are broadly dispersed through the central nervous system, and to a lesser degree, also to other organ systems. Nachi: Because CB receptors are concentrated within the central nervous system, they exert the majority of their effects on the neuropsychiatric systems. And   -- yes that’s a double ding -- the cannabinoid 1 (or CB1) receptor is most responsible for cannabis-induced neuropsychiatric effects. Jeff: Interestingly, the anti-emetic effects and possible palliative properties of cannabis derivatives are thought to be secondary to the inhibitory effects on serotonin receptors and the excitatory effects on the transient receptor potential vanilloid 1 (or TRPV1).  More on TRPV1 later... Nachi: So far we have been talking about cannabinoids from the cannabis plant, but with cannabis being illegal in many states, there has been a growing emergence of synthetic cannabinoids. Synthetics were initially developed in the 1980s largely for research purposes. Jeff: Because the current DEA controlled substances schedule designations are based on original chemical names, synthetics have gained popularity as manufacturers are able to produce newer compounds and circumvent DEA designation as well as routine urine drug screening tests. Nachi: You may be familiar with some of the street names for synthetics -- like spice, K2, scooby snacks, black mamba, kush, and kronic. These can often be purchased over the internet or through specialty smoke shops. Jeff: Scooby Snacks, what a fantastic name, mooovingggg on… Synthetic cannabinoids often have greater affinity for the CB1 receptor than naturally occurring cannabinoids -- and synthetics can produce 100 times the effect. As a result, the presenting symptoms with synthetic intoxication can be difficult to differentiate from crystal meth or bath salt abuse. Nachi: Manufacturers sometimes use solvents and other contaminants. Clusters of toxic ingestions and deaths have occurred. Emergency clinicians need to be aware of this and should report suspicious events immediately. Jeff: For more on synthetic intoxications in the ED, be sure to take a look at the recent May 2018 issue of Pediatric Emergency Medicine Practice on Synthetic Drug Intoxication in Children if you haven’t already read it. Also, just a quick FYI - If you’re not a current subscriber to Pediatric Emergency Medicine Practice, we’re giving away a free copy of the issue specifically for our listeners. Just head over to ebmedicine.net/drugs for the PDF of the issue. Nachi: A free issue for our listeners, that’s nice! Let’s move on to a discussion about current indications for cannabinoids. So, there is no clear consensus on these indications, but there is some research of varying quality that supports the treatment of some chronically debilitating diseases with cannabinoids. Jeff: A systematic review and meta-analysis from 2015 found low-quality evidence to support cannabis therapy for appetite suppression in HIV and aids patients; moderate-quality evidence for treatment of chronic pain and spasticity; and also moderate quality evidence for some chronic debilitating diseases. Nachi: While talking about evidence-based medicine here, another review by the National Academies of Science, Engineering, and Medicine on possible associations between cannabis and cancers arising in the lungs, head, and neck, or testicles -- showed no statistically significant associations exist. Jeff: So in case that wasn’t clear - the overall evidence to support cannabis therapy, in general, is weak. Also, be aware that there are various formulations of cannabis that allow for different routes of administration. We’re talking oils, tinctures, teas, extracts, edibles like candies and baked goods, parenteral formulations, eye solutions, intranasal, sublingual, transmucosal, tablets, sprays, skin patches, topical creams, rectal suppositories, and capsules -- just to name, a few. Nachi: A few! That seems pretty complete to me. Basically, any way you can imagine, it seems like a route of administration has been explored. But of importance, these formulations have different absorption times -- as you might expect. The shortest duration to peak plasma levels of delta-9-THC is through the inhalation route, which can produce effects within 3 minutes. On the longer end, rectal cannabis administration can take up to 8 hours to reach peak plasma concentrations. Jeff: Let’s talk about some of the clinical findings and systemic effects associated with cannabis use. First up is the link between cannabis use and stroke or TIA. Cannabis users who smoked at least once weekly had a 3.3 times higher risk of stroke or TIA. Nachi: And there is moderate quality evidence that this link may be dose-dependent. Larger amounts of cannabis use lead to cerebral vasospasm and a reduction in cerebral blood flow. Jeff: In terms of psychiatric effects, several low-to-moderate quality studies have shown statistically significant associations between psychosis and self-reported cannabis use. Some association between high potency cannabis or synthetic cannabinoid use with new-onset psychosis or relapse in previous psychiatric disorders has also been found. Lastly, there is weak data supporting a correlation between cannabis use and depression. Nachi: From a cardiovascular standpoint, cannabis use is associated with increased resting heart rate, hypertension, and decreases in the anginal threshold for patients with chronic stable angina. A 2001 study described an augmented risk of myocardial infarction within the first hour of cannabis use and found an almost 5-fold increase in those who reported smoking cannabis at least weekly when compared to those who smoked monthly or less. Jeff: Dysrhythmias, qt prolongation, av blocks, myocarditis, and sudden death have all been reported with cannabinoids. Nachi: In terms of pulmonary effects, these are not really related to cannabis use directly, but rather the smoke inhalation and combustion materials of synthetic cannabinoids. Effects from chronic use can be seen. Jeff: Renally speaking, acute kidney injury and rhabdomyolysis are associated with synthetic cannabinoids and have been observed in several case reports. The rhabdo is believed to be due, in part, to associated seizures, muscle tremors, and agitation. Nachi: Among metabolic abnormalities, patients can present with hyperthermia, hypoglycemia, hypokalemia, hyponatremia, and metabolic acidosis. Jeff: Orally and dentally, dry mouth is the most common finding in acute cannabis toxicity. Chronic use has also been linked to severe periodontitis. Nachi: And ophthalmologically, there is, of course, the commonly seen conjunctival injection. Cannabis has also been found to decrease intraocular pressure when used topically -- and of note, there have also been rare reports of acute angle closure glaucoma and central retinal vein occlusion. Jeff: While talking about clinical findings and systemic effects of cannabis use, we certainly need to go over cannabinoid hyperemesis syndrome (or CHS), which is -- quite simply put -- associated with frequent visits to the ED in chronic users. It presents with nausea, vomiting, and abdominal pain. Nachi: CHS is commonly misdiagnosed as cyclical vomiting syndrome. After the legalization of marijuana in Colorado, it was reported that nearly twice as many patients had presented for what was thought to be cyclical vomiting syndrome. And ironically, though cannabis has been used as an anti-emetic, chronic use can cause the opposite reaction, leading to CHS, which is typically refractory to traditional anti-emetics. Jeff: And the etiology of CHS is not well understood. Similarly, the exact criteria for CHS are poorly defined. It presents as a recurrent and relapsing disorder that can be divided into 3 phases: prodromal, hyperemetic, and recovery. Nachi: In the prodromal phase, patients complain of early morning nausea without vomiting, and they can have mild abdominal discomfort. This can last from months to years. In the hyperemetic phase, patients complain of severe, unremitting abdominal pain with repeated episodes of vomiting and retching. This is often associated with an inability to tolerate po. Jeff: The hyperemetic phase lasts 24-48 hours and can lead to dehydration, electrolyte abnormalities, and weight loss. Patients may learn to relieve symptoms by compulsively bathing in hot water. Nachi: Resolution of symptoms is seen when the patient stops using cannabis. This is during the recovery phase, which can last from days to months. But this can be short-lived if the patients begin using cannabis again. Jeff: On that note, we should also touch on cannabis withdrawal. Termination of heavy and habitual use can lead to withdrawal syndromes within 48 hours. Symptoms here include irritability, anxiety, restlessness, sleep difficulty, seizures, and aggression. Medications that can be helpful include benzodiazepines, neuroleptic agents, and quetiapine in refractory cases. Nachi: Moving on to the next sections in the article, let’s talk about differential diagnosis and prehospital care. The differential for acute cannabinoid intoxication, as you might suspect, is broad, and it includes some life-threatening processes. We won’t list them here, but be sure to think broadly before deciding on cannabis as the cause of your patient’s symptoms. Jeff: For the prehospital providers -- care here is mainly supportive. Provide airway protection as needed - gather information from the patient’s environment, looking for empty pill bottles or another empty packaging. Nachi: Let’s move on to care once in the ED. All patients who are in distress and suspected of drug ingestion should be disrobed completely and placed on a cardiac monitor. Fully assess for trauma and place an IV in the patient. Search the patient’s clothing for drugs and paraphernalia, which may help in making the diagnosis. Jeff: When getting a complete history from the patient, it may also be worthwhile to talk with any persons accompanying the patient to the ER for more information. In your history, be sure to ask about a pattern of use and possible co-ingestions. Nachi: When considering cannabis hyperemesis syndrome, a detailed history and physical exam are crucial for making the diagnosis. To differentiate between other etiologies of abdominal pain and vomiting, be sure to ask about the use of hot baths for relief, resolution of symptoms after stopping cannabis use, and the predominance of symptoms in the morning hours. Jeff: On physical exam, for cannabis intoxication, there isn’t a particular toxidrome to look for. Monitor vital signs closely, looking out for alterations in blood pressure and heart rate. A complete neurologic and mental status examination will be the key here. Nachi: Decisions for lab testing should be dependent on the patient’s presentation. Possible tests include CBC, BMP, LFT’s, lipase, cpk, ckmb, troponin, urinalysis, urine drug screening, serum tox screens (for alcohol, aspirin, and acetaminophen), and any other drug levels for medications that the patient is taking for medicinal purposes, like phenytoin or lithium levels. Jeff: One study supported point of care urine drug testing in the ED. However, know that acute cannabis intoxication can be difficult in the chronic user, as delta-9-THC will be present in urine for up to 24 days. Testing for synthetically derived cannabinoids is difficult due to changes in synthetic compounds. Nachi: Interestingly, there are a number of medications that are associated with false positive cannabinoid screenings. These include ibuprofen, pantoprazole, efavirenz, and lamotrigine. Jeff: For any patient arriving with suspected cannabis or synthetic abuse, consider checking an EKG. You’re looking for signs of ischemia, arrhythmia, and interval abnormalities. Serum and urine tox tests are not particularly helpful in the acute chest pain patient who is using synthetic marijuana. Nachi: Not surprisingly, there are no specific diagnostic imaging modalities to help diagnose cannabis or synthetic cannabinoid intoxication. But imaging may help with assessing other disease states on a patient’s differential, so stay mindful of that. Jeff: Now that we’ve talked about history, physical exam, and useful testing modalities, let’s talk about treatment for cannabis and synthetic cannabinoid toxicity… therapy is primarily focused on supportive care. Most ED visits only require a short stay. Nachi: That’s right, there are no antidotes to give for treatment here. Be sure to look for and treat dehydration, acute renal failure, and rhabdo though. In severe cases of neuropsychotropic effect, give benzodiazepines, like lorazepam, to help with control. Jeff: For GI effects, first-line treatment is traditional anti-emetics like ondansetron or metoclopramide. Recent literature and case reports have shown significant improvement with butyrophenones like haloperidol as a second-line treatment. Nachi: While talking about treating the gastrointestinal effects of cannabis toxicity, let’s also discuss methods to control cannabinoid hyperemesis syndrome. The mainstays for treatment here are actually supportive therapy and cessation of cannabis use. Jeff: And can you tell us more about why these patients crave hot showers and improve after? Is there a pathophysiology or mechanism to know about there? Nachi: There is a well-studied theory here and it relates to the TRPV1 receptor that we talked about earlier. Temperatures in excess of 109 degrees Fahrenheit, acidic conditions, and compounds found in certain foods and plants (like cannabis) activate this receptor. It’s believed that intermittent and repetitive exposure to agonists of the TRPV1 receptor leads to a persistent state of nausea and vomiting. Desensitization of the receptor happens after repeated stimulation, and repetitive topical capsaicin or hot water is believed to function as an exogenous agonist. Jeff: In any case of repetitive emesis, be sure to consider electrolyte replacement if needed. In many cases, hydration or repletion will need to happen through an IV. Proton pump inhibitors can also help in some cases where GI symptoms are a dominating complaint of the patient. Nachi: Recent literature supporting the use of haloperidol for nausea and vomiting has found that symptoms improve approx 1hr after administration. This can decrease the need for observation or admission. Jeff: Haloperidol works via dopamine 2 receptor antagonism. D2 receptors are found in high concentrations throughout the nervous system and bind with high affinity to haloperidol. The suggested starting dose is 2.5mg IV with a repeat dose of 5mg IV if needed. An RCT is underway in Canada on the use of ondansetron versus haloperidol with an estimated completion of July 2019. Nachi: Capsaicin has similarly shown promise in cannabis hyperemesis syndrome through the TRPV1 receptor as we discussed already. Currently, there are no dosing recommendations or application instructions for capsaicin. There is some evidence supporting relief within 30 to 45 minutes, and capsaicin can be applied topically to any nonmucosal surface like the abdomen, chest, or back. Jeff: So to recap -for cannabis hyperemesis syndrome, treat with anti-emetics, PPI’s, electrolyte repletion, and IV hydration as needed. As a second line treatment, consider haloperidol and topical capsaicin applied to the chest, abdomen, or back. Nachi: Let’s talk about some special populations next -- starting with Pediatrics. According to data from 2012, of the 130 million people reporting illicit drug use within their lifetime, 25% were children between 12 and 17 years of age. Jeff: And according to the national poison data system, states with marijuana use laws have seen a 30% increase in calls related to marijuana use by children. From 2010 to 2011, the number of ED visits by children aged 12 to 17 years old due to synthetic cannabinoid use also has doubled. Nachi: Many children and adults believe that synthetic cannabinoids don’t pose serious health risks, as these are not illegal to purchase. And this class of drugs is particularly attractive to adolescents since it will not readily test positive on urine drug tests. All of this is very concerning for emergency clinicians. Jeff: There have been several recent reports of myocarditis in association with marijuana use. One case resulted in death due to myocyte necrosis after an unknown amount of edible marijuana was consumed by a toddler. Nachi: Horrific! Jeff: And the exact mechanism through which the myocardial necrosis happens isn’t known. Nachi: For all children and adolescents who present to the ED with alteration in mental status, psychosis, or chest pain -- be sure to screen for cannabis or synthetic cannabinoid use.  There are case reports in the pediatric literature of STEMIs seen in patients without pre-existing cardiac disease or risk factors. Jeff: Keep in mind that urine drug screens can be falsely positive from certain proton pump inhibitors, so if possible, assess a urine drug screen prior to starting a PPI in these patients. Nachi: Moving on to our next special population… pregnant women. Know that it can be difficult to the differential between hyperemesis gravidarum and cannabis hyperemesis syndrome in pregnant patients. Ask specific questions regarding marijuana use before and during the pregnancy. Jeff: It’s also worth noting that cannabis is known to cause adverse outcomes on babies such as low birth weight and more frequent perinatal ICU placement. Nachi: Let’s move on to the final major section of the article, which is on the legal status of cannabis and cannabinoids. Much of the controversy surrounding cannabis for medicinal use relates to the absence of quality evidence. More research is needed to evaluate potential public health risks posed by variations in quality and potency, potential impact to our healthcare system, and ability to legislate for synthetic cannabinoids. Jeff: Though marijuana and all whole-plant derivatives are schedules I controlled substances, there are a few cannabinoid-based drugs approved by the FDA for medicinal purposes -- with lower schedule designations. Dronabinol is a schedule III drug derived synthetically from delta-9-THC. It’s used in chemotherapy-induced nausea/vomiting, as well as anorexia and weight loss from AIDS/cancer. Nachi: Nabilone, a schedule II synthetic variant of THC, has been approved in the treatment of aids-related anorexia and chemotherapy-induced nausea also. Jeff: Nabiximols, a plant-derived cannabinoid, has been approved in Europe and Canada for multiple sclerosis induced spasticity and cancer-related pain. Nabiximols are not yet approved in the US. Nachi: And lastly, we should mention cannabidiol, which is a schedule I controlled substance approved for treatment of seizures with 2 rare diseases -- Lennox-gastaut syndrome and dravet syndrome. Compared with placebo alone cannabidiol and other medications have shown efficacy in lowering the rate of seizures for these diseases. Jeff:  Lots of interesting stuff to look out for there in cannabinoid-related medications. Alright, on to disposition - Nachi: Most patients who present with uncomplicated acute cannabis or synthetic cannabinoid intoxication can be observed until clinically sober. Discharge home should be in the care of a sober family member or friend. Make sure that the patient knows not to operate vehicles or heavy machinery under the influence of drugs. Counsel them on drug abuse also. Jeff:   In more rare situations, patients will require admission. Consider this particularly for patients who have end-organ damage, rhabdomyolysis, acute renal failure -- evidence of cardiovascular, cerebrovascular, or ophthalmologic insults -- intractable vomiting, or acute psychosis. Nachi: And for cannabinoid hyperemesis syndrome, patients may require admission for IV hydration and electrolyte correction. Once the patient is tolerating PO and lab derangements have been corrected, they can be discharged. Jeff: Let’s wrap up the episode with key points and clinical pearls… N: Marijuana is the most commonly used illicit substance in the US. States that have legalized marijuana for medical and recreational purposes are showing increased rates of marijuana abuse and dependence. J: When concerned with drug intoxication, search your patient’s clothing for drugs and paraphernalia on arrival. N: The neuropsychiatric and addictive properties of cannabis are due primarily to delta-9-THC. J: Synthetic cannabinoids have gained popularity as manufacturers are able to produce newer compounds and circumvent DEA designations as well as routine urine drug screening tests. N: Manufacturers of synthetic cannabinoids sometimes use solvents and other contaminants, which have caused clusters of toxic ingestions and death. J: The shortest duration to peak plasma levels of delta-9-THC is through the inhalational route. Effects can be seen within 3 minutes. N: Cannabis users who smoke at least once weekly can have a 3.3 times higher risk of stroke or TIA. J: The risk of myocardial infarction is increased within the first hour of use, and there is an almost 5-fold increase for individuals who smoke at least once per week. N: Acute kidney injury and rhabdomyolysis have been noted with synthetic cannabinoid use in several case reports. J: Cannabis intoxication is associated with many metabolic abnormalities like hyperthermia, hypoglycemia, hypokalemia, hyponatremia, and metabolic acidosis. N: Cannabis hyperemesis syndrome, which presents with abdominal pain and vomiting, is associated with frequent visits to the ED in chronic users. J: The mainstay for treatment of cannabis hyperemesis syndrome is supportive therapies and cessation of cannabis use. N: Patients with cannabis hyperemesis syndrome crave hot showers because of activation of the TRPV1 receptor. J: Topical capsaicin may also help in the treatment of cannabis hyperemesis syndrome through activation of the TRPV1 receptors. N: Haloperidol at 2.5mg IV may help in refractory vomiting associated with cannabis hyperemesis syndrome. J: Many children and adults do not believe synthetic cannabinoids pose serious health issues as the they are not illegal to purchase. This is incorrect. N: Most patients with acute uncomplicated cannabis intoxication can be observed and discharged. Admit if there are any signs of end organ damage, intractable vomiting, or acute psychosis. Jeff: So that wraps up the August 2018 episode of Emplify. Nachi: For those of you looking for CME - the address for this months credit is ebmedicine.net/E0818, so head over there right away to get the credit you deserve.  Remember that the you heard throughout the episode corresponds to the answers to the CME questions. Jeff: And don’t forget to grab your free issue of Synthetic Drug Intoxication in Children at ebmedicine.net/drugs specifically for emplify listeners. Feel free to share the link with your colleagues or through social media too. See you next time! Most Important References 5. * Kim HS, Monte AA. Colorado cannabis legalization and its effect on emergency care. Ann Emerg Med. 2016;68(1):71-75. (Literature review; 21 studies)7. * Baron EP. Comprehensive review of medicinal marijuana, cannabinoids, and therapeutic implications in medicine and headache: What a long strange trip it’s been …. Headache. 2015;55(6):885-916. (Review)9. * Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015;313(24):2456-2473. (Retrospective chart review; 4 cases)64. * Tournebize J, Gibaja V, Kahn JP. Acute effects of synthetic cannabinoids: update 2015. Subst Abus. 2016:1-23. (Systematic review; 46 articles, 114 patients)83. * Wallace EA, Andrews SE, Garmany CL, et al. Cannabinoid hyperemesis syndrome: literature review and proposed diagnosis and treatment algorithm. South Med J. 2011;104(9):659-664. (Review)

In this episode we focus on the presentation, diagnosis and treatment of acute coronary syndromes. From unstable angina to STEMIs, we have it covered! 

Author: Don Stader, M.D. Educational Pearls While we usually associate the coronary vasculature with STEMIs, there are other pathologies that can affect the heart’s blood supply. Kounis syndrome: an allergic vasospasm of the coronary arteries. This can happen post anaphylaxis or be caused by a stent allergy. It is best treated with aggressive management of the allergic reaction. Kawasaki disease: An autoimmune condition that presents in kids as conjunctivitis, lymphadenopathy, hand/foot swelling, rash, and fever. It can also cause coronary aneurysms, which can rupture and be rapidly fatal.   Prinzmetal angina: Caused by coronary vasospasm. Presents with transient chest pain at rest. Treat with CCBs. Cocaine: Causes coronary vasospasm. Cocaine-induced vasospasm is best treated with BZDs. Coronary artery dissection: increased risk in pregnant women and those with connective tissue disorders. References:  Memon S, Chhabra L, Masrur S, Parker MW. Allergic acute coronary syndrome (Kounis syndrome). Proceedings (Baylor University Medical Center). 2015;28(3):358-362.

Dr. Carolyn Lam:               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.                                                 Today's issue features striking results from the ASSERT 2 trial of the prevalence of subclinical atrial fibrillation detected with implantable monitors in a group of high-risk older individuals. Much more soon, right after these summaries.                                                 The first original paper in this weeks' journal shows for the first time that myocardial edema, in the week after STEMI in humans, is a bimodal phenomenon. First off, there is Dr. Fernandez Jimenez and Barreiro-Perez, corresponding author Dr. Ibañez, and colleagues from CNIC in Madrid, Spain, evaluate that the time course of edema reaction in 16 patients with anterior STEMIs successfully treated by primary angioplasty compared to 16 matched controls using cardiac magnetic resonance and assessing its implications for myocardium at risk quantification. The STEMI patients were scanned serially within the first three hours after reperfusion and at, one, four, seven and 40 days, while controls were scanned once. Furthermore, they performed an experimental study of 20 pigs undergoing 40 minute ischemia reperfusion, followed by serial cardiac magnetic residence exams at 120 minutes, one, four and seven days after reperfusion.                                                 The authors found that am initial wave of edema appeared abruptly at reperfusion, but it was significantly attenuated by 24 hours. The initial wave of edema was followed by a second or differed healing related wave of edema several days after reperfusion, reaching a plateau around four to seven days after myocardial infarction. Of note, cardiac magnetic resonance myocardium at risk quantification at 24 hours post-reperfusion severely underestimated the infarct size.                                                 In summary, post-MI edema in patients follows a bimodal pattern, which affects cardiac magnetic resonance in estimates of myocardium at risk. The dynamic changes in post-STEMI edema, highlight the need for standardization of cardiac magnetic resonance timing to retrospectively delineate myocardium at risk and quantify myocardial salvage. According to the present clinical and experimental data, a time window between day four and seven, post-MI, seems a good compromise for standardization. However, further studies are needed to study the effect of other factors on these variables.                                                 The next paper sheds light on molecular mechanisms underline the progression of atherosclerosis, involving multiple inflammatory events, as well as the counteraction by inflammatory responses in cells such as the endothelium, circulating monocytes and resident macrophages in the arterial wall.                                                 Co-first authors, Dr. Li and Martin, corresponding author Dr. Shyy from Xi'an Jiaotong University Health Science Center and University Health Science Center and University of California, San Diego and colleagues, analyzed RNA seek data to identify cholesterol oxidation and e-flux genes regulated by Kruppel-like factor 4, which is a key anti-inflammatory transcription factor. They found that Kruppel-like factor 4 upregulates cholesterol 25 hydroxylase and liver X receptor in vascular endothelial cells and macrophages. In further in vitro and in vivo experiments, they show that access enhanced reverse cholesterol transport from the vascular wall, mitigated inflammation through suppression of sterile regulatory binding protein two and NOD-like receptor family hiring pyrin domain containing protein three inflammasome in endothelial cells and also promoted cholesterol e-flux in M1 to M2 transition in macrophages.                                                 In summary, Kruppel-like factor 4 trans-activates cholesterol 25 hydroxylase and liver X receptor, promoting the synergistic effects between individual cells and macrophages to protect against atherosclerosis susceptibility, and this may therefore be a therapeutic target for cardiovascular disease.                                                 The next study provides data on the safety and efficacy of a novel cobalt alloy-based coronary stent eluting the antiproliferative agent, ridaforolimus, for treatment of patients with coronary artery disease.                                                 Dr. Kandzari from Piedmont Heart Institute in Atlanta, Georgia and colleagues, reported the primary results of the bionics trial, which was a prospective international, one-to-one randomized trial conducted to evaluate in a noninferiority design, the relative safety and efficacy of ridaforolimus-eluting stents compared to slow release zotarolimus-eluting stents among 1,919 patients at 76 centers undergoing PCI. At 12 months, the primary endpoint of target lesion failure was 5.4% for both devices, thus meeting the prespecified criteria of noninferiority of ridaforolimus stent compared to the zotarolimus stent.                                                 Angiographic and intravascular ultrasound measures of restenosis, late lumen loss and nepintimal hyperplasia measured at 13 months, were similar in both devices. Treatment with the ridaforolimus-eluting stent resulted in low rates of myocardial infarction, repeat revascularization and stent thrombosis, and results were consistent in predefined patients and lesion groups. The authors therefore concluded that these results support the safety and efficacy of ridaforolimus-eluting stents in patients representative of every day clinical practice.                                                 Well, that wraps it up for your summaries. Now, for our future discussion.                                                 Today for our future discussion, we are going to talk about a true global public health problem. It's a condition that affects 33 million people worldwide, a number that is expected to double by 2050, and what we're talking about is atrial fibrillation. Those are the numbers of just what we know of detected atrial fibrillation, but today's paper deals with silent subclinical atrial fibrillation and the results of the ASSERT 2 trial. I'm so pleased I have the first and corresponding author with us today, Dr. Jeff Healey from Population Health Research Institute at McMaster University in Hamilton, Ontario. Welcome, Jeff. Dr. Jeff Healey:                 Good morning. Dr. Carolyn Lam:               Also on the show today is Dr. Sami Viskin, associate editor from Tel Aviv Medical Center. Hi, Sami. Dr. Sami Viskin:                 Hi. Hello, everybody. Dr. Carolyn Lam:               Jeff, from ASSERT to ASSERT 2, could you give us a bit of the picture of what made you do ASSERT 2 and what have we learned? Dr. Jeff Healey:                 The ASSERT trial was a large 2,500 patient trial in patients in with pacemakers and also implantable defibrillators and it was really an easy first place to study this entity of sub-clinical atrial fibrillation because, of course all of these patient had implanted devices with electrodes in their atrial where they could report all of the internal activity continuously for many years at a time. This was done with really no incremental costs or inconvenience to the patient, the data were already being collected, so in ASSERT we asked the question, how common is atrial fibrillation as it is not detected clinically and is it associated with stroke? What we found was that over time, somewhere between 30% and 40% of patients with an implemented device developed atrial fibrillation, which we termed subclinical atrial fibrillation, because this was not detected by the usual clinical mean. Great results, very interesting, but begged the question, is this a unique entity that we see only in pacemaker patients or if you just took older individuals in the more general population, would you see subclinical atrial fibrillation as well? That was really the impetus for doing that ASSERT 2 trial in patients who are over the age of 65, had cardiovascular condition, placed them at increased risk or stroke in atrial fibrillation, but did not have implanted devices. Dr. Carolyn Lam:               Indeed, Jeff. That's a beautiful set up. The ASSERT was really quite a landmark study suggesting that what we know as clinical may be just the tip of the iceberg, isn't it? Now you've extended it, and I think it'd be really important for the audience to understand that ASSERT 2 was really a high risk cohort. Could you maybe tell us a little bit more of what you did and what more we learned? Dr. Jeff Healey:                 Sure. These were typical patients who might be attending a cardiology clinic, an outpatient general medicine clinic who did not have pacemakers and did not have any history of atrial arrhythmias, but you're right, they were high-risk. These were patients over 65 who have had clinical risk factors, things like hypertension, or diabetes, but also some other marker of increased risk such as a BNP that was elevated or left atrial enlargement. Dr. Carolyn Lam:               Yeah and your findings were so striking. Tell us. Dr. Jeff Healey:                 What was quite was surprising was, indeed, we found that in the non-pacemaker, non-defibrillator population from ASSERT 2, we also found high prevalence of subclinical atrial fibrillation. This was really quite surprising. In fact, it was many times higher than we had predicted. We found that over time, the annual risk of developing atrial fibrillation in this cohort was 34.4% per year, which is truly astounding number of patients who developed atrial fibrillation. Dr. Carolyn Lam:               That's like one in three of such patients experiencing at least one of these episodes lasting at least five minutes? That's really impressive. Dr. Jeff Healey:                 It was high.  You could look into that study and find groups where the risk was even higher, so we chose to cut off left atrial volume of 58 millimeters and not correspondent with the median volume of the population series of Olmstead County for people over the age of 65 who came in for an echocardiogram, and that was the minimum left atrial size to get into the trial. If you then looked at within the ASSERT 2 trial and looked at the volumes within the trial, somewhere around 72 1/2 milliliters, if you looked at the patients who had the top of atrial size, that risk was as high 50% per year, so one in two. Dr. Carolyn Lam:               Another thing I noticed though about your results is that the frequency of these episodes, it's not that frequent, and so what we would do typically in a 24-hour monitoring or even a seven-day monitoring would have captured only a small proportion of these. Isn't that the case, Jeff? Could you give us some numbers there? Dr. Jeff Healey:                 Yes, of course. The episodes that qualified were at last five minutes in duration, we then do longer episodes in course, but these were much less frequent in the single digit percent risk, and what we found was there were, as you say, quite infrequent. So with the standard 24-hour halter monitor, for example, you would have had a very low pickup. It really goes to show that the longer you monitor, the more you will find. I think that's the key message out of this study and other studies like it.                                                 I think conversely, you also have to realize that the more you look, or the harder you look, you may be uncovering atrial fibrillation that behaves differently than atrial fibrillation you find, for example, in the single 12 lead ECG. We have found, and others have found, that the risk of stroke we find when we would have short episode picked up only with long term continuous monitoring is real but it's much lower than we see with atrial fibrillation that was picked up by ECB where patients are presenting in emergency rooms stroke with symptoms. Dr. Carolyn Lam:               That's such relevant points, and it really brings up the unanswered questions perhaps, exactly what is the correlation with stroke risk? What should we do about it? Sami, I'm sure you have other questions when you handle this paper and we had so many discussions among the editor, would you like to just start the ball rolling in some of these considerations? Dr. Sami Viskin:                 Well, actually, we understood from the beginning of the study was not powered to show any difference in outcome by intervention, by treating any of these patients that had discovered atrial fibrillation with anticoagulation, so we took this paper as what it is, a paper that shows the unexpectedly high privileges of atrial fibrillation in patients who have neither symptoms nor electrocardiographic documentation of atrial fibrillation when they undergo implantation of our recording device. So we took this paper for what it is, a very interesting finding that opens the door for new studies, testing perhaps the value of intervention with anticoagulation at an earlier stage. Dr. Carolyn Lam:               Yeah, I agree. I'd love to hear Jeff's thoughts on what those next steps may be, but just to point out to the audience, I mean, at the moment, our decisions on whether to anti-coagulate, like the CHADSVASC score and so on, doesn't really take into account the type of atrial fibrillation or the duration of atrial fibrillation? Does it? What do we do now? What do we do in the context of the fact that results, like the COMPASS trial, that maybe just based on the presence of vascular disease, we should anti-coagulate, right? Jeff, how about your thoughts? What are the next steps? Dr. Jeff Healey:                 You're right. I mean, is there a value for empirically anticoagulating individuals. That's really going to boil down to the individuals with an absolute risk of stroke and how well they do on anticoagulants. Good question.                                                 In the post-stroke world or post-cryptogenic stroke, which we now report to as [inaudible 00:16:48], these individuals are being evaluated with two large clinical trials, looking at this idea of just empiric anticoagulation with low dose, NOAC in comparison to aspirin.  These trials are ongoing, and they expect to report findings by the end of 2018.                                                 In the general population, no such large scale trial is ongoing at the present time. You mentioned COMPASS and the big COMPASS results were clearly a big result at the European Society meeting, but it must be clarified that the dose of NOAC or rivaroxaban used in COMPASS was not the typical dose that we would use in the treatment of patients with atrial fibrillation, so much lower. I think we have to be careful when we're talking about doses that may be different 5 to 10 fold and what is then coagulating a patient and what is not. I think, certainly, I would not consider the COMPASS tests right now to be an effective atrial fibrillation dose, but as we've discussed, subclinical atrial fibrillation is different and we may have further data in the future.                                                 Now, how do we get there? I think many people are aware of two ongoing trials, the ARTESIA trial, which is run by our group, the NOAH-AF Trial run by Kirchof and the group from Birmingham and the AF-NET organization, and these two ongoing trials have taken this question back again, so the pacemaker population that we are enrolling thousands of patients with pacemakers and defibrillators who have these short episodes, and they're being randomized treatment with a full dose new oral anticoagulant vs aspirin. These trials are ongoing, and I think these trials and the pacemaker population will actually give us the answer to what is the risk benefit for treating, so interesting course of event. We started in the pacemaker population to show there was risk for these short episodes, that this was hotly debated 10 - 15 years ago, and now we take ASSERT 2 and other trials into the non-pacemaker population to show that this is actually a problem for older individuals in general, and now the third step, go back into the pacemaker clinic again and to do trials to study the effectiveness in therapy. Dr. Carolyn Lam:               Great point and great takeaways. How about, Sami? What do you think would be the take-home message for clinicians at this moment based on what we know now and based on this new data? Dr. Sami Viskin:                 Well, the message is clear, the message is that atrial fibrillation is far more prevalent than what we think it is, the message is that for every event of atrial fibrillation that we feel we probably have many events that we don't feel we should be distrustful about judging the decision to anti-coagulate or not based on symptoms, and I'm referring now to patients who already have one event documented of atrial fibrillation and are waiting until they feel the next one, before they start taking anti-coagulations. This is another warning about how we should be careful about trusting symptoms when deciding to treat and when not to treat. I just said this opens a new door for a new line of studies, looking at how early to intervene with anticoagulation, what dosage should be used for these patients who probably have lower burden of atrial fibrillation. If you can see that the patients who have atrial fibrillation documented on the electric cardiogram, as patients who simply have a higher burden and therefore they are more likely to come up with documentation on a regular ACG, so perhaps those only have subclinical atrial fibrillation have a lower burden, perhaps they can benefit from lower doses of anticoagulation, but these are all fit, that need to be proven by trials. Dr. Jeff Healey:                 It is not only an issue for implanted devices but with the implantable cardiac monitors, this is now relevant for many other patients who have these devices implanted for things like syncope, but also there's been a lot of progress in the last 5 to 10 years on surface-attached based monitors or other types of monitors that can be with patients for days, weeks and even months, and we're all grappling with this in clinical medicine, what to do with a person with 25 beats of an atrial tachycardia or 37 seconds on a 30-day monitor? It's all an issue of the density, the burden of arrhythmia, and we do believe there is some gradience in the risk of stroke ... You're right, the treatment is not obvious, but we should take our treatment for patients who are in atrial fibrillation a lot or all the time, and simply apply it upstream like, that we may have very different treatment or approaches that are more tailored to individual patient risk. Dr. Carolyn Lam:               Thanks, Jeff, and thank you so much, Sami. Congratulations, Jeff. We discussed a lot of other questions that need to be answered, but you've really opened the door to look at some of these questions with your paper today and we're really very proud to be publishing your paper in this week's journal.                                                 Thank you very much, listeners for joining us this week. Don't forget to tune in again next week.  

Dr. Carolyn Lam:               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. Today's feature paper looks at the early use of N-Acetyl Cysteine with nitrate therapy in patients undergoing primary PCI for STEMI. More soon right after this week's summary of original articles.                                                 The first paper identifies a novel association between Phosphatidyl Choline Transfer Protein, or PCTP expression, in the blood, and death or myocardial infarction in patients with cardiovascular disease. Now, PCTP regulates intermembrane transfer for phosphatidyl choline. Platelet PCTP expression has been shown to be associated with increased platelet responses upon activation of protease-activated receptor four thrombin receptors. In today's paper, first authors Dr. Mao and Songdej, corresponding author Doctor Rao, and colleagues from the Temple University School of Medicine in Philadelphia used DNA protein binding studies and human erythroleukemia cells, as well as luciferase reporter studies to show that PCTP is a direct transcriptional target of RUNX1, a major hematopoietic transcription factor that regulates platelet production and function. Furthermore, in 587 patients with cardiovascular disease, the authors showed that PCTP expression in the blood correlated with RUNX1 expression and was independently associated with future death or myocardial infarction. Thus, regulation of PCTP by transcription factor RUNX1 may play a role in the pathogenesis of platelet-mediated cardiovascular events.                                                 The next paper provides molecular insights into cardiac fibrosis and shows that bone marrow cells are involved in cardiac fibrosis during pathological stress. Drs. Kishore, Verma and colleagues from Lewis Katz School of Medicine and Temple University of Philadelphia hypothesize that interleukin-10 inhibits pressure overload-induced homing of bone marrow fibroblast progenitor cells to the heart, and inhibits their trans-differentiation to myofibroblasts, thus attenuating cardiac fibrosis. To test this hypothesis, the authors used pressure-overload in wild-type and interleukin-10 knockout mice by transverse aortic constriction, and used chimeric mice to determine bone marrow origin. They further isolated fibroblast progenitor cells from mouse bone marrow for mechanistic studies.                                                 They found that, in addition to resident cardiac fibroblasts, bone marrow-derived fibroblasts significantly contributed to progression of pathological cardiac fibrosis, and that pliotropic antiinflammatory interleukin-10 inhibited the recruitment and trans-differentiation of bone marrow fibroblast progenitor cells in the pressure-overloaded myocardium. At a molecular level, they showed that interleukin-10 inhibited TGFβ SMAD2-3 signaling in activated bone marrow fibroblast progenitor cells. Furthermore, inhibition of TGFβ SMAD2-3 signaling mediated micro-RNA21 maturation was a novel mechanism by which interleukin-10 inhibited bone marrow progenitor cells-mediated cardiac fibrosis. Thus, selective inhibition of bone marrow cells homing to the heart and of fibrotic signaling using interleukin-10 or selective RNAs might inhibit the transition of physiological hypertrophy to heart failure, and may be a potential therapeutic target to treat or prevent the development of hypertrophic remodeling.                                                 The next study looks at the risk of major bleeding in patients receiving ticagrelor compared to Aspirin after a TIA or Acute Ischemic Stroke in the SOCRATES study. As a reminder, the SOCRATES trial was the first outcome study with ticagrelor in patients with Acute Ischemic Stroke or TIA, who were given ninety days of monotherapy with ticagrelor, 90 milligrams, twice daily and compared with those given aspirin 100 milligrams daily. The trial found that ticagrelor was not superior to aspirin in reducing the primary composite endpoint of stroke myocardial infarction or death. In today's study, Dr. Easton and colleagues from University of California San Francisco aimed to describe the bleeding profile of monotherapy with ticagrelor versus aspirin in this population of patients with Acute Ischemic Stroke and TIA, to characterize major bleeding based on the PLATO, TIMI and GUSTO bleeding definitions, and to identify factors associated with major bleeding.                                                 They found that PLATO major bleeds occurred in 0.5% of patients on ticagrelor and 0.6% of patients on aspirin. The most common locations of major bleeds were intracranial and gastrointestinal. Intracranial hemorrhage was reported in 12 patients, or 0.2%, on ticagrelor and 18 patients, or 0.3%, in aspirin. Independent of bleeding classification, PLATO, TIMI or GUSTO, the relative difference between treatments for major or severe bleedings was similar. However, non-major bleeds were more common on ticagrelor. Thus, this paper contributes important data on the bleeding profile of ticagrelor in patients with acute cerebral ischemia, provides some reassurance that there's no increased risk of major bleedings with ticagrelor compared to aspirin, including intracranial bleeds, however, a numerical increase in minor bleedings with ticagrelor.                                                 The next paper tells us that single 24-hour urine collections may be useful for estimation of average sodium intake in populations. However, for a reliable estimation of cardiovascular and renal risk, multiple 24-hour urine collections may be needed. First author, Dr. Olde Engberink, corresponding author, Dr. Vogt and colleagues from Academic Medical Center Amsterdam selected 574 adults with EGFR above 60, an outpatient 24-hour urine sample, and at least one collection during a seventeen year follow-up. Sodium intake was estimated using a single baseline collection, and the average of samples that were collected during a one, five, and fifteen year follow-up.                                                 They found that estimates of daily sodium intake changed more than 0.8 grams in half of the subjects when using multiple follow-up collections instead of a single baseline collection. The way of estimating sodium intake significantly affected the observed relationship between sodium intake and long-term outcome. Hazard ratios for cardiovascular and renal outcomes changed up to 85% when multiple follow-up 24-hour urine collections were used, instead of a single baseline collection. Thus, in summary, relative to a single baseline, the use of subsequent 24-hour urine samples resulted in different estimations of an individual's sodium intake, while population averages remained similar. This had significant consequences for the association between sodium intake and long-term cardiovascular and renal outcome.                                                 That wraps it up for your summaries this week. Now to our featured discussion.                                                 Today for our featured discussion, we are talking about approaches to cardio protection. Now, we all know that the mortality rates in STEMI has improved over the last few years, because we've gotten better at reperfusion therapy with primary PCI, as well as effective secondary prevention therapy. However, the incidents and severity of heart failure following STEMI has been rising and thus, cario-protective therapies are of great interest to prevent heart failure and improve overall clinical outcomes following STEMI, following primary PCI. Over the years, a number of cardio-protective therapies have been tried, but have either been unable to reduce MI size or improve clinical outcomes following STEMI, but in this week's journal, we have an exciting trial, very interestingly of two old cardio-protective therapies showing a lot of promise in this area. And to do discuss this, I am so pleased to have the corresponding author, Dr. John Beltrame from University of Adelaide in Australia, as well as associate editor from Brigham and Women's Hospital in Boston, Massachusetts, Dr. Laura Mauri.                                                 John, you know, in my introduction I said this is very interesting. You're actually combining two old therapies, N-acetylcysteine and nitroglycerin in your approach in this trial. Now, both these drugs have been around for a long time. Please share with us what led you to think that a combination would work, what made you test the combination, and what makes your trial different from the other reperfusion studies before. Dr. John Beltrame:           So, nitroglycerin, of course, has been utilized to treat myocardial infarctions for many years, has been shown to reduce the chest pain in that scenario, but little reward in perhaps reducing infarct size. And one of the main benefits of that people don't know is the vasodilation effect that it has on the coronary arteries, as well as reducing the wall stress. So, what we thought to combine it with N-acetylcysteine, which potentiates nitroglycerin effects, but also is a free radical scavenger. So therefore it would actually also work on reperfusion injuries. So these have a very synergistic effect, and therefore we expected to have good benefits.                                                 The ... because we're also looking at an anti-ischemic therapy with a reperfusion protective therapy, we wanted to introduce it as soon as possible. And so this drug was initiated in the emergency department as patients arrived, and then taken off to the cath lab where it was continued. We also began to ensure that we had adequate N-acetylcysteine, which I'll probably refer to as NHC from now on, as much on board as possible before we actually opened the artery. We gave high dose N-acetylcysteine at 20 milligrams in the first thirty minutes, and then at a slower rate for the next twenty-four hours. So for the first hour we gave it at 20 milligrams a minute, and then thereafter 10 milligrams a minute. And then, the actual study. We had patients randomized and double-blind placebo control trial, multiple sites here within South Australia with the primary endpoint being myocardial infarct size on early cardiac MRIs.                                                 So they got to see the opportunity to have a smaller sample size than many of the conventional infarct studies, and the key finding was in that early MRI, we saw an absolute 5% reduction in infarct size, which was an exciting find for us and this we expect to translate to a significant reduction in cardiovascular events and that's where I guess we're going in the future, is that we need to now undertake a study where we show that the combination of these two drugs also impacts on cardiac events. Dr. Carolyn Lam:               How beautifully summarized, John. And really, congratulations on such an impactful and elegantly done study. I like the way you highlight it, though. Basically, you gave this drug earlier than most other trials of reperfusion therapies, because you gave it even before the primary PCI procedure as most cardio-protective strategies were tried within the cath lab. Would that be accurate? Dr. John Beltrame:           Exactly right. So, whereas a number of the studies would take the patient with the STEMI to the cath lab, undertake the diagnostic angiogram and the diagnostic angiogram would then confirm that this was occluded, then they would introduce the cardio-protective agent and then proceed on to open up the artery. Whereas we had an opportunity for sort of ... at least twenty to thirty minutes before the artery was opened to actually have those drugs on board. And so, in a number of cases, we improved the patency of the vessel when we got to the diagnostic angiogram. So it's a two-point strategy, one anti-ischemic and one cardio-protective in terms of reperfusion injury. And we think that future trials in this area need to address both those conditions. Dr. Carolyn Lam:               I can think of no better person to comment on being able to do these trials and the future of these trials than Laura. Laura, what are your thoughts? Dr. Laura Mauri:               Thanks Carolyn. John, that was a great summary and I think you're really to be commended, because this is just such a challenging area to be doing trials in, but that's really what we need. And you know, most of the trials have focused on early procedure success for therapies that we currently use, rather than showing documented benefit in longer-term endpoints. But as you mentioned earlier, Carolyn, we really do still have patients who would benefit from therapies that may reduce infarct size. I think it's really remarkable, John, that your study was able to intervene early in the emergency room, as we know as clinicians that's not easy to do, not only to activate the quick pathways of care that we need for STEMI, but then on top of that to lay on a randomized trial, but I think it's incredibly important.                                                 What are you foreseeing as the challenges? As you think about your next steps in rolling this out to a ... potentially a larger trial and implementing such a study? Dr. John Beltrame:           As with many trials, it's ways of recruitment, because a study like this is not gonna be funded by industry, you need to be looking at ... here within Australia, be looking at government authorities to put in an application for funding and then, it's a matter of recruiting. That's one of challenges we came across in doing this particular study, and this relates particularly, I guess, to the MRI endpoint, is the number of patients that were claustrophobic and therefore we couldn't actually perform the cardiac MRI, and so your primary endpoint ... you missed out. And so again, there's going to be frustrations like that and a much larger trial, which will need to involve even more centers. But funding that's ... for much of the research, I guess, it will be the challenge, because we've got two agents as Carolyn mentioned in the beginning that have been around for a long time and are certainly unlikely to attract any industry funding. Dr. Carolyn Lam:               John, I have a question about the design as well. Of the current and maybe a future trial, because I'm left with the question, was it your early intervention? Was it the outcome you chose? Or was it one drug or the combination? And so, you did not do a factorial design in this trial. Are there plans to look at that, or do you the combination ... it's so obvious that two separate drugs don't need to be tested? Dr. John Beltrame:           Very good question. So, you're quite correct, we can't be absolutely confident in terms of the mechanism, because we had one opportunity, I guess, to do the study and so we wanted to keep a simplified design, and that's what we gave everyone; a background of nitroglycerin and then just randomized the N-acetylcysteine. But we think it's actually the combination of the two that makes the benefits, because as you would be aware, the synergistic benefits is that the N-acetylcysteine potentiates the effect of the nitrates, potentiates the vasodilating properties, potentiates it's anti-platelet properties also. And so we think it's a combination of the two. Dr. Laura Mauri:               John, it's interesting ... the use of the cardiac MRI endpoint, as we've all seen, it's being used more and more frequently, but at the same time, it's new for us, right? So you've raised some of the challenges and the practical execution of getting patients who can tolerate it, especially after an acute hospitalization. But the classical endpoint has been SPECT imaging as a surrogate endpoint for mortality in myocardial infarction. Of course, that's based on very large trials showing correlation, but the MRI should really give much better resolution, so I think that's really a very logical next step. But I think the more data that we get across multiple different trials, the better we can validate that endpoint and see how it might differ from the classical surrogate endpoints that we've had for myocardial infarction.                                                 Other than the efficiency of looking at MRIs, do you have other observations when you look at MRIs at endpoint compared with some of the traditional endpoints like SPECT? Dr. John Beltrame:           Not SPECT so much, but to follow on exactly what she was saying, we all also measured serum creatine kinase, so CK, values. And because of the larger spread of the data and therefore the need to have a larger sample size, although we certainly saw a trend of improvement in CKs as a marker of infarct size, we didn't achieve statistical significance, but with the MRI because we had more precise measurements, that gave us a smaller margin of error and therefore, we were able to see a difference between the two treatments. So certainly I think in the future, the MRI is certainly a very good way to evaluate agents in this particular area. Dr. Laura Mauri:               It's nice to see the consistency that you saw across the different endpoints. Dr. Carolyn Lam:               That's true, but I do have a question though, as an Echo cardiologist here, your three-month assessment of the ventricular remodeling, if I read it right, there was no change detected at three months. Would you like to comment on that? Dr. John Beltrame:           What we saw in terms of the infarct size, we still saw a difference. I think what you might be referring to, the infarct size was a little bit smaller, so that's just ... over time the we feel like the scar contracts down. But I'm not sure if you're also referring to the ... Dr. Carolyn Lam:               LV dimensions and injection fraction. Dr. John Beltrame:           The injection fraction's interesting, because when we looked at that ... because we found no difference in the injection fraction. Now, if you take a look at the actual values, they're almost normal and I think that says something to where we are in terms of the management of acute STEMIs, because we preserved the left ventricular function, because there were normal ejection fractions, so we couldn't make them better than what we had in placebo, so that is something to primary PCI, I think. Dr. Carolyn Lam:               That's a great answer. Thank you, John. And Laura? Dr. Laura Mauri:               John, your group is really to be commended for conducting such a high-quality trial in this very challenging area. We've been victims of our own success, I think, in this space because the mortality rates have obviously declined after MI, infarct size is on the decline with early reperfusion. Getting in there with attempted therapies is a race when you're also trying to achieve fast door-to-ballon times, but it's still an important area and one we can only address with careful, randomized trials with important therapies. So I want to congratulate you and your group, it's really a step in the right direction. Dr. Carolyn Lam:               You've been listening to "Circulation On The Run", thank you so much for joining us, and don't forget to tune in next week!  

 A recent study in Academic Emergency Medicine by Hughes and colleagues, looks at the potential clinical relevance of having emergency physicians sign ECGs read "normal" by the computer software.  FOAM reviews of this article can be found here: Dr. Smith's ECG blog Emergency Medicine Literature of Note REBEL EM Then we review ischemia on ECGs, including STEMIs as well as a dive into ischemic T waves Check out FOAMcast.org for more show notes and images. Thanks for listening! Lauren Westafer and Jeremy Faust

Dr. Carolyn Lam:               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. We have such a special issue today. You see, it's entirely focused on resuscitation and I am delighted to have with me today, Associate Editor, Dr. Mark Lane from Puffs Medical Center, who really put this issue together. Welcome, Mark. Dr. Mark Lane:                  Thank you Carolyn. Dr. Carolyn Lam:               Mark, maybe you could start by telling us why the focus on resuscitation? I do believe this is the first time we've done this at Circulation. Dr. Mark Lane:                  Yes, this is the first time we've done this at Circulation. It really was a confluence of a couple things coming together. Once is that over the spring and summer, we had a very high volume of high quality resuscitation papers come to Circ. This was not something that we actually asked for but we noted that there were a number of these. Also, it's an important time in resuscitation because a number of the resuscitation counsels across the world have called for improvements in the survival rate, noting that we already have the tools that we need to increase survival and we have to better apply these tools. The HA has provided a goal of doubling resuscitation and resuscitation counsels in Europe, New Zealand and Australia have also echoed that call. Dr. Carolyn Lam:               That's great, so this is a really important issue. I just echo your words about their being a remarkable number of original papers. We have seven and they're just such high quality. Let's chat through them, shall we? I'm going to go by pre-hospital setting to the out of hospital setting and finally end up in the in-hospital setting. Shall we do that? Dr. Mark Lane:                  That sounds great. Dr. Carolyn Lam:               The first paper is really about identifying patients at risk for pre-hospital sudden cardiac death at the early phase of myocardial infarction. You want to tell us a bit about that one? Dr. Mark Lane:                  This is a study coming from the emergency medical services in the greater Paris area, where they looked at their cardiac arrest and STEMIs over the last seven or eight years. What they were specifically looking at is, can you identify STEMI patients who are at risk for having a cardiac arrest, because if you could identify those patients, you'd want to get there very quickly because if you know they're going to arrest or they're going to have a cardiac arrest, then having a defibrillator there would be very important.                                                 What they found, is that you can actually identify STEMI patients who are higher likelihood of arrest and those STEMI patients are those with younger age, they're not obese, they don't have diabetes. They have shortness of breath in addition to their chest pain and they have a very short delay from the time of chest pain to their call EMS. That is they're very concerned about their chest pain. You could use these characteristics to predict which STEMI patients, which chest pain patients were at highly likelihood of having a cardiac arrest. There was as much as a 19-fold difference between individuals without any of these factors and individuals with several of these factors. Dr. Carolyn Lam:               What I like about this, is that simplicity of that score. Age, symptoms and kind of the absence of diabetes, absence of obesity and that short time frame. It's something that could be asked on a routine questionnaire by EMS dispatchers, for example. Dr. Mark Lane:                  Right. It highlights the importance of the dispatch system. That simple questions, you can really stratify risk and it's not just getting an ambulance out there. Truly stratifying risk in order to get there quicker. Dr. Carolyn Lam:               There are two papers that deal with out of hospital cardiac arrest. One of them interestingly focusing on the neuro-protective effects of Glucagon-Like Peptide-1 analog Exenatide. Thoughts about that one? Dr. Mark Lane:                  This is a randomized study from Denmark. Notable that there are very low number of randomized trials in resuscitation so the fact that they did this is remarkable. What they did, is this glucagon-like peptide analog is a type II diabetic medicine and there is some reason to believe that that may protect the brain after resuscitation and ROSP. They had two goals in this trial. One was to see if it was feasible to administer a drug within six hours of a cardiac arrest and the other was to get any sort of outcome measure of whether this could provide some benefit. They randomly assigned 120 comatose patients and half of them got the peptide analog and the other half did not. What they showed, it is feasible to give IV administration of a drug within six hours of a cardiac arrest. Unfortunately, the drug they used did not appear to have any clinical benefit and this was both a composite end-point of death in neurologic function but also an evaluation of a brain neuron specific amylase, which was actually brain damage so they didn't see any biological or clinical neuro-protective effects of this drug. Dr. Carolyn Lam:               I didn't realize it until you said it, it is very difficult to do a randomized control trial. This is very significant just for that. The next study about the out of hospital arrest, really talks about bystander CPR and I think seeks to answer to what degree bystander CPR remains positively associated with survival with increasing time to potential defibrillation. Important question, what do you think of that? Dr. Mark Lane:                  It's an important question that surprisingly has not been evaluated that closely. Most either studies either look at bystander CPR or EMS arrival times but don't look at the interaction between the two. This study looks at the interaction between bystander CPR and EMS response time and that's the critical thing in this paper that's very interesting.                                                 What they did is, they split bystander CPR with or without and then EMS response times five minutes, 10 minutes and longer. If EMS responds within five minutes and you had bystander CPR, the survival rates with good neurological outcome were 14.5%, which is really a remarkable number. If there was no bystander CPR and the EMS arrived within five minutes, it dropped to 6.3%. There was 2.3-fold higher likelihood of good neurologic survival with bystander CPR with EMS within five minutes.                                                 They also looked at the 10 minute response time of EMS and if you had bystander CPR and EMS arrived within 10 minutes, the survival rate was 6.7% and without bystander CPR, it was 2.2%. With bystander CPR and EMS arrival within 10 minutes, there was a three-fold higher likelihood of survival with bystander CPR. It's interesting that by 13 minutes, there really was essentially no difference in those individuals who had bystander CPR or not, suggesting that at that point it's taken so long for EMS to arrive, it really doesn't make really much difference between whether you have bystander CPR.                                                 A really important paper showing that bystander CPR is critical, but so is EMS arrival within five minutes especially, but even 10 minutes. Dr. Carolyn Lam:               I like that paper and I really like the way you crystallized the findings so clearly like that. What I'm also liking is the way, even though these papers weren't invited or anything, there is this nice flow because from bystander CPR we now talk about duration of resuscitation. There's one regarding adults and followed by one in pediatric population so very nice set of papers. Could we start by maybe talking about the adult one? The one looking at the association between duration of resuscitation and favorable outcomes after out of hospital cardiac arrest from North America. Dr. Mark Lane:                  The reason that these two papers are important is really the futility issue. When is it futile to continue a CPR and that's a very important question. This adult paper is from the ROC Consortium. The ROC is a North American Seer NIH Sponsored consortium that's been going on over the last 10 or so years. What they looked at was outpatients and they had a very large number of greater than 11,000 subjects and of those 8% survived with a good outcome. That's 8% of those 11,000. If you looked at those 8% that survived, 90% of those had return of spontaneous circulation with 20 minutes. You really wanted to get their blood pressure back within 20 minutes.                                                 If you went beyond 20 minutes to the return of spontaneous circulation, you still could get good outcome. It was less likely but it was more likely if you had initial shockable rhythm, you had a witnessed cardiac arrest or you had bystander CPR. If you had some of those features, then you would argue to continue CPR for a longer time period. Actually a very nice important paper that if you had those other three features, you could still get good neurologic functioning, even with resuscitation attempts up to 40 minutes. Dr. Carolyn Lam:               Exactly. I thought I saw 47 minutes somewhere, but it gives us a bit of a guidance when we're making these really tough decisions and talking about tough decisions and futility, I think it's even more amplified in the pediatric population, isn't it? This next paper from Japan talks about the duration of pre-hospital CPR in the pediatric population. What are your thoughts on that one? Dr. Mark Lane:                  This was a study from Japan, using their nation-wide Japanese data base. Actually, in many ways mirrored the adult experience. The number of patients analyzed with roughly the same. This was nearly 13,000. They looked at 30 day survival both overall and 30 day survival with good neurologic function and 30 day survival overall were 9% so similar to the 8% in adults and good neurologic function were 2.5%, which wasn't quite as good as in the adults and that the duration of CPR also was very important. Once CPR went out to 42 minutes there was less than 1% chance that that individual was going to survive with any significant neurologic outcome. If you had bystander CPR you could increase that time by four to five minutes but again showing very similar numbers to the adult population that once you start hitting that 40 to 45 minute time frame, if there's no return of spontaneous circulation then the odds of survival are really quite low.                                                 The time frame may be extended a bit by CPR, maybe be extended by a bit if you had a shockable rhythm. Again, very similar features to what were found in the adult study. Dr. Carolyn Lam:               What a nice pair of papers. You know, the pediatric paper was paired by yet another, wasn't it? This one now addresses very importantly conventional versus compression only CPR in the pediatric population. Again, from Japan. I know both the pediatric papers were of great interest because you invited an editorial on this as well. You want to comment on those? Dr. Mark Lane:                  This issue of compression only CPR versus standard CPR, which includes compression and ventilation is a very hot one because we know that if you can do compression only CPR, the individuals willing to do that type of CPR are much greater than the individuals willing to do mouth to mouth. In the adult population, there's been a number of very good retrospective registries and also randomized trials that showed that compression only CPR may be very similar ... In fact some studies better, some studies a little worse than compression-ventilation CPR.                                                 Whether this applies to the pediatric population is not clear. There is more asphyxial arrest in the pediatric population whereas in the adult it's more cardiac so there is concern that compression only CPR will not be as good in children. This group of investigators used the same registry. A little shorter time-frame. They looked at it for two years and thus only had 2,000 patients in this registry. Of these 2,000 patients 400 received conventional CPR, 700 received compression only CPR and 1,000 did not receive any CPR. The important findings in this study was that any CPR increases survival so if you did not get any CPR, your survival was 3.7%. If you got conventional CPR your survival was 25.9% and if you got compression only CPR your survival was 9.3%.                                                 When you compared unadjusted survival with compression only versus the standard CPR, the odds ratio were 3.42 that standard CPR was better than compression only CPR. However when you did multi-variable adjustment, that big difference decreased and was no longer statistically significant between conventional CPR and compression only CPR. The same was true when you did propensity score matching which is an attempt to randomize to match groups. There was really no difference between conventional CPR and and compression only CPR.                                                 From this study, it's clear that any CPR is better than no CPR. There was a hint here that standard CPR was better than compression only CPR but because that improvement disappeared with multi-variable adjustment and propensity score matching both the authors and the editorialists have called that it's time for a randomized trial of compression CPR in kids. Dr. Carolyn Lam:               Very nice. That brings us already, to the last original paper. Into the in-hospital setting and it talks about time to epinephrine. That's nice. We've got time to balloon and time to door and and now we've got time to epinephrine. Tell us about this one. Dr. Mark Lane:                  This was a very nice study from the guidelines database. This is a data base that the HA is using to evaluate resuscitation in hospitals. In this database, the investigators looked at times to the epinephrine administration and then overall patient survival for the hospitals. What they found is that there was wide variability in the time to first epinephrine dose. The HA and other counsels have recommended that it be given as soon as possible or early-on in resuscitation and in this database 12.7% of patients had delays greater than five minutes to epinephrine.                                                 What importantly they showed, when you looked at the hospital's overall time to epinephrine administration and the hospital's overall resuscitation survival rates, they were inversely proportional. That is, the longer that hospitals took to give the first dose of epinephrine, the lower their survival rate. This really leads to a very important question, is it the delay in epinephrine administration that makes the difference between these good functioning hospitals and poor functioning hospitals, or is it that the delay to epinephrine administration is really a surrogate for poor CPR performance. I suspect that both of them could be true, although I suspect the second one is probably a higher likelihood. Dr. Carolyn Lam:               Congratulations again on this amazing issue with extremely important take-home messages just from the original papers. Were there other papers you wanted to highlight in this issue? Dr. Mark Lane:                  Yeah, there were three research letters and this is a newer type thing for SERP. These are original manuscripts but in a very succinct fashion in that they're making a single point. I actually thought these three research papers were very interesting also. One was on the mechanical CPR in the cares database and in this paper they actually showed that mechanical CPR was associated with poor outcomes in resuscitation so a paper well worth reading. In another paper from France looked at pulmonary embolism related to sudden cardiac death and what they found is that PEs were present in a significant percentage of people who had sudden cardiac arrest and again if you had a non-shockable rhythm, female, prior thromboembolism or absence of heart disease you were more likely to have a pulmonary embolism.                                                 The final research letter looked at ticagrelor versus clopidogrel in comatose patients undergoing PCI, a randomized study. Succinct paper well worth reading. In addition to those three research letters, there were four frames of reference. These are more a personal perspective on resuscitation and resuscitation signs over time and interesting reading, all four of them. Dr. Carolyn Lam:               Mark, that was a beautiful summary and I am sure you've whet the appetites of all the listeners to just grab hold of this issue. Thank you so much for joining me today. Thank you listeners for tuning in and don't forget to tune in next week.

FOAMcast will be back shortly with regular core content-cutting edge mash ups; however, we wanted to take a moment to focus on a conference that inadvertently created FOAMcast...and is coming to Chicago in June 2015.  SMACC - Chicago (#smaccUS) June 23-26, 2015. Registration begins Nov 5, 2014 There are too many core content lectures to choose from and they're available on iTunes. Our favorites are listed on FOAMcast.org and here we review: Dr. Haney Mallemat - The Art and Science of Fluid Responsiveness Dr. Scott Weingart - Sepsis in New York: Our First 15,000 Patients Dr. Cliff Reid - Resuscitation Dogmalysis Dr. Rob Mac Sweeney - ARDS: An Evidence Based Update Timing, Tribes, and STEMIs  

Vic Brazil opens smaccGOLD with a powerful insight into how conflict between "tribes" in our everyday working environment can adversely impact upon patient care.