{"version":"1.0.0","segments":[{"startTime":0.17,"endTime":3.24,"body":"[intro music]"},{"startTime":3.24,"endTime":5.63,"body":"[Dr. Handy] Hi, welcome"},{"startTime":3.24,"endTime":5.63,"body":"to Harrison's Podclass"},{"startTime":5.63,"endTime":8.78,"body":"where we discuss important"},{"startTime":5.63,"endTime":8.78,"body":"concepts in internal medicine."},{"startTime":8.78,"endTime":9.92,"body":"I'm Cathy Handy."},{"startTime":9.92,"endTime":11.64,"body":"[Dr. Wiener] And I'm Charlie"},{"startTime":9.92,"endTime":11.64,"body":"Wiener, and we're coming to you"},{"startTime":11.64,"endTime":13.69,"body":"from the Johns Hopkins School of Medicine."},{"startTime":16.06,"endTime":17.53,"body":"[Dr. Handy] Welcome to today's episode,"},{"startTime":17.53,"endTime":20.27,"body":"a 57-year-old with chest discomfort."},{"startTime":20.27,"endTime":21.72,"body":"[Dr. Wiener] Great, Cathy,"},{"startTime":20.27,"endTime":21.72,"body":"well, we're going to have"},{"startTime":21.72,"endTime":23.53,"body":"another guest discussion today,"},{"startTime":23.53,"endTime":26.55,"body":"so looking forward to"},{"startTime":23.53,"endTime":26.55,"body":"that, but here's the case."},{"startTime":26.55,"endTime":27.936,"body":"You're in the emergency department"},{"startTime":27.936,"endTime":31.46,"body":"seeing a 57-year-old hockey"},{"startTime":27.936,"endTime":31.46,"body":"team coach with a prior history"},{"startTime":31.46,"endTime":34.86,"body":"of hypertension,"},{"startTime":31.46,"endTime":34.86,"body":"hyperlipidemia, and tobacco use."},{"startTime":34.86,"endTime":36.89,"body":"He presents to the emergency"},{"startTime":34.86,"endTime":36.89,"body":"department tonight after"},{"startTime":36.89,"endTime":39.66,"body":"experiencing chest"},{"startTime":36.89,"endTime":39.66,"body":"discomfort during a practice."},{"startTime":39.66,"endTime":42.4,"body":"He tells you that he first"},{"startTime":39.66,"endTime":42.4,"body":"began having similar symptoms"},{"startTime":42.4,"endTime":44.0,"body":"about three weeks ago when he was"},{"startTime":44.0,"endTime":46.29,"body":"skating vigorously during practice."},{"startTime":46.29,"endTime":48.6,"body":"The discomfort typically"},{"startTime":46.29,"endTime":48.6,"body":"lasts about 10 minutes,"},{"startTime":48.6,"endTime":50.69,"body":"but then it resolves every time with rest."},{"startTime":50.69,"endTime":52.16,"body":"However, over the last week,"},{"startTime":52.16,"endTime":54.79,"body":"it's taken less exertion"},{"startTime":52.16,"endTime":54.79,"body":"to initiate the discomfort"},{"startTime":54.79,"endTime":57.57,"body":"and a longer time for it to dissipate."},{"startTime":57.57,"endTime":60.17,"body":"Tonight, it occurred while he"},{"startTime":57.57,"endTime":60.17,"body":"was just sitting on the bench"},{"startTime":60.17,"endTime":61.71,"body":"and his assistant coach insisted"},{"startTime":61.71,"endTime":63.55,"body":"that he come to the emergency department."},{"startTime":63.55,"endTime":66.283,"body":"He describes the discomfort"},{"startTime":63.55,"endTime":66.283,"body":"as a pressure radiating"},{"startTime":66.283,"endTime":68.84,"body":"to his jaw, but since being"},{"startTime":66.283,"endTime":68.84,"body":"in the emergency department,"},{"startTime":68.84,"endTime":70.317,"body":"it has resolved also."},{"startTime":70.317,"endTime":72.02,"body":"[Dr. Handy] This is the"},{"startTime":70.317,"endTime":72.02,"body":"classic description of"},{"startTime":72.02,"endTime":74.43,"body":"cardiac chest pain, so I"},{"startTime":72.02,"endTime":74.43,"body":"would definitely begin workup"},{"startTime":74.43,"endTime":77.08,"body":"for that and starting with an EKG."},{"startTime":77.08,"endTime":79.26,"body":"[Dr. Wiener] Okay, well, it"},{"startTime":77.08,"endTime":79.26,"body":"turns out at triage on entry"},{"startTime":79.26,"endTime":81.6,"body":"they did that, and his"},{"startTime":79.26,"endTime":81.6,"body":"electrocardiogram shows"},{"startTime":81.6,"endTime":84.878,"body":"T wave inversions in leads"},{"startTime":81.6,"endTime":84.878,"body":"I, II, aVL, V5, and V6."},{"startTime":84.878,"endTime":87.552,"body":"T wave inversions in leads"},{"startTime":84.878,"endTime":87.552,"body":"I, II, aVL, V5, and V6."},{"startTime":87.552,"endTime":89.584,"body":"There are no ST elevations."},{"startTime":89.584,"endTime":92.25,"body":"[Dr. Handy] So not an ST"},{"startTime":89.584,"endTime":92.25,"body":"elevation MI or a STEMI,"},{"startTime":92.25,"endTime":94.295,"body":"but he could still be"},{"startTime":92.25,"endTime":94.295,"body":"having an acute event."},{"startTime":94.295,"endTime":95.87,"body":"He does have changes that you mentioned,"},{"startTime":95.87,"endTime":98.57,"body":"an old EKG would be essential to compare."},{"startTime":98.57,"endTime":101.075,"body":"[Dr. Wiener] So his last ECG"},{"startTime":98.57,"endTime":101.075,"body":"was two years ago on a routine"},{"startTime":101.075,"endTime":103.609,"body":"physical examination, and"},{"startTime":101.075,"endTime":103.609,"body":"these T wave inversions"},{"startTime":103.609,"endTime":104.783,"body":"are clearly new."},{"startTime":104.783,"endTime":106.55,"body":"[Dr. Handy] Anything"},{"startTime":104.783,"endTime":106.55,"body":"more from physical exam"},{"startTime":106.55,"endTime":108.03,"body":"or history that's noteworthy?"},{"startTime":108.03,"endTime":110.99,"body":"I'd want to make sure that"},{"startTime":108.03,"endTime":110.99,"body":"his vital signs are stable,"},{"startTime":110.99,"endTime":112.5,"body":"his pulses are symmetric,"},{"startTime":112.5,"endTime":115.25,"body":"and that he doesn't have any"},{"startTime":112.5,"endTime":115.25,"body":"localizing cardiac, respiratory"},{"startTime":115.25,"endTime":116.96,"body":"or any neurologic findings."},{"startTime":116.96,"endTime":119.5,"body":"[Dr. Wiener] Okay, good. Well,"},{"startTime":116.96,"endTime":119.5,"body":"he's awake and responsive."},{"startTime":119.5,"endTime":122.05,"body":"He's worried but in no apparent distress."},{"startTime":122.05,"endTime":124.73,"body":"He was placed on nasal oxygen at triage."},{"startTime":124.73,"endTime":127.46,"body":"His blood pressure is 140/90 in both arms,"},{"startTime":127.46,"endTime":128.75,"body":"his heart rate is 100,"},{"startTime":128.75,"endTime":131.36,"body":"his respiratory rate is 12,"},{"startTime":128.75,"endTime":131.36,"body":"and his oxygen saturation"},{"startTime":131.36,"endTime":133.89,"body":"is 100% on the nasal oxygen."},{"startTime":133.89,"endTime":136.15,"body":"His pulses are present in both legs."},{"startTime":136.15,"endTime":138.57,"body":"His jugular venous"},{"startTime":136.15,"endTime":138.57,"body":"pressure is not elevated,"},{"startTime":138.57,"endTime":140.31,"body":"his lungs have no crackles,"},{"startTime":140.31,"endTime":142.71,"body":"and the only abnormality"},{"startTime":140.31,"endTime":142.71,"body":"on cardiac examination"},{"startTime":142.71,"endTime":145.84,"body":"is a diffused PMI and a loud S4."},{"startTime":145.84,"endTime":148.34,"body":"He moves all of his"},{"startTime":145.84,"endTime":148.34,"body":"extremities symmetrically,"},{"startTime":148.34,"endTime":151.75,"body":"and he's alert and oriented"},{"startTime":148.34,"endTime":151.75,"body":"to person, place, and time."},{"startTime":151.75,"endTime":153.56,"body":"[Dr. Handy] So those are"},{"startTime":151.75,"endTime":153.56,"body":"all reassuring findings."},{"startTime":153.56,"endTime":156.43,"body":"He's clearly not in cardiogenic"},{"startTime":153.56,"endTime":156.43,"body":"shock and does not seem to"},{"startTime":156.43,"endTime":158.39,"body":"be having a stroke or a dissection,"},{"startTime":158.39,"endTime":160.09,"body":"let's tackle the question next."},{"startTime":160.09,"endTime":162.5,"body":"[Dr. Wiener] So the question"},{"startTime":160.09,"endTime":162.5,"body":"asks, which of the following"},{"startTime":162.5,"endTime":165.41,"body":"clinical entities is an"},{"startTime":162.5,"endTime":165.41,"body":"appropriate diagnosis"},{"startTime":165.41,"endTime":168.64,"body":"for this hockey coach?"},{"startTime":165.41,"endTime":168.64,"body":"And the options are,"},{"startTime":168.64,"endTime":172.798,"body":"A. more information is required"},{"startTime":168.64,"endTime":172.798,"body":"before making a diagnosis;"},{"startTime":172.798,"endTime":176.973,"body":"B. non-ST elevation myocardial infarction;"},{"startTime":176.973,"endTime":180.527,"body":"C. ST elevation myocardial infarction;"},{"startTime":180.527,"endTime":184.85,"body":"D. stable angina;"},{"startTime":180.527,"endTime":184.85,"body":"or E. unstable angina."},{"startTime":184.85,"endTime":186.83,"body":"[Dr. Handy] So of those"},{"startTime":184.85,"endTime":186.83,"body":"choices, the answer is A."},{"startTime":186.83,"endTime":189.58,"body":"more information is required"},{"startTime":186.83,"endTime":189.58,"body":"before we make a diagnosis,"},{"startTime":189.58,"endTime":192.41,"body":"and even before we would decide"},{"startTime":189.58,"endTime":192.41,"body":"on any of the other choices"},{"startTime":192.41,"endTime":193.45,"body":"that you mentioned."},{"startTime":193.45,"endTime":194.58,"body":"[Dr. Wiener] Why do you say that?"},{"startTime":194.58,"endTime":196.31,"body":"[Dr. Handy] Well, let's go"},{"startTime":194.58,"endTime":196.31,"body":"through each of the answers"},{"startTime":196.31,"endTime":198.26,"body":"and rule out some of them, so it's not C."},{"startTime":198.26,"endTime":201.37,"body":"I mentioned already, he's not"},{"startTime":198.26,"endTime":201.37,"body":"having an ST elevation MI,"},{"startTime":201.37,"endTime":203.41,"body":"and his ECG rules that out."},{"startTime":203.41,"endTime":206.46,"body":"He could still be having an"},{"startTime":203.41,"endTime":206.46,"body":"acute coronary syndrome or ACS"},{"startTime":206.46,"endTime":208.78,"body":"based on the clinical presentation alone."},{"startTime":208.78,"endTime":211.85,"body":"Typically, in an ACS, the"},{"startTime":208.78,"endTime":211.85,"body":"chest discomfort is severe,"},{"startTime":211.85,"endTime":213.95,"body":"and it has at least one of"},{"startTime":211.85,"endTime":213.95,"body":"the following three features."},{"startTime":213.95,"endTime":217.48,"body":"It occurs with rest or with"},{"startTime":213.95,"endTime":217.48,"body":"minimal exertion, lasting greater"},{"startTime":217.48,"endTime":220.94,"body":"than 10 minutes, it's a"},{"startTime":217.48,"endTime":220.94,"body":"relatively recent onset,"},{"startTime":220.94,"endTime":223.3,"body":"so within the past couple"},{"startTime":220.94,"endTime":223.3,"body":"of weeks, for example,"},{"startTime":223.3,"endTime":226.21,"body":"or it occurs with a crescendo"},{"startTime":223.3,"endTime":226.21,"body":"pattern where it's distinctly"},{"startTime":226.21,"endTime":227.39,"body":"more severe, prolonged,"},{"startTime":227.39,"endTime":229.71,"body":"or more frequent than previous episodes."},{"startTime":229.71,"endTime":232.11,"body":"[Dr. Wiener] So that certainly"},{"startTime":229.71,"endTime":232.11,"body":"sounds like our patient, right?"},{"startTime":232.11,"endTime":234.01,"body":"[Dr. Handy] Absolutely,"},{"startTime":232.11,"endTime":234.01,"body":"but the question was asking"},{"startTime":234.01,"endTime":235.13,"body":"for more specificity,"},{"startTime":235.13,"endTime":238.16,"body":"so the diagnosis of"},{"startTime":235.13,"endTime":238.16,"body":"non-ST segment elevation"},{"startTime":238.16,"endTime":241.07,"body":"myocardial infarction, or"},{"startTime":238.16,"endTime":241.07,"body":"an NSTEMI is established"},{"startTime":241.07,"endTime":243.31,"body":"if a patient with the clinical"},{"startTime":241.07,"endTime":243.31,"body":"features that we described"},{"startTime":243.31,"endTime":245.645,"body":"above of ACS also develops evidence"},{"startTime":245.645,"endTime":248.32,"body":"of myocardial necrosis,"},{"startTime":245.645,"endTime":248.32,"body":"and that means that"},{"startTime":248.32,"endTime":250.55,"body":"you would see abnormally elevated levels"},{"startTime":250.55,"endTime":252.88,"body":"of biomarkers of cardiac necrosis."},{"startTime":252.88,"endTime":254.39,"body":"In this case, we didn't hear anything"},{"startTime":254.39,"endTime":255.63,"body":"about laboratory values,"},{"startTime":255.63,"endTime":257.72,"body":"so we'd not be able to say this right now."},{"startTime":257.72,"endTime":260.3,"body":"[Dr. Wiener] So, he clearly"},{"startTime":257.72,"endTime":260.3,"body":"does not have stable angina"},{"startTime":260.3,"endTime":262.11,"body":"based on the worsening symptoms, right?"},{"startTime":262.11,"endTime":263.53,"body":"[Dr. Handy] Right, his"},{"startTime":262.11,"endTime":263.53,"body":"clinical presentation"},{"startTime":263.53,"endTime":264.67,"body":"is also consistent though"},{"startTime":264.67,"endTime":266.72,"body":"with accelerating or unstable angina,"},{"startTime":266.72,"endTime":269.67,"body":"but we can't distinguish between"},{"startTime":266.72,"endTime":269.67,"body":"NSTEMI or unstable angina"},{"startTime":269.67,"endTime":271.61,"body":"without the cardiac biomarkers."},{"startTime":271.61,"endTime":273.72,"body":"If we drew them and they were elevated,"},{"startTime":273.72,"endTime":275.49,"body":"then he would be having an NSTEMI."},{"startTime":275.49,"endTime":277.65,"body":"[Dr. Wiener] And I presume"},{"startTime":275.49,"endTime":277.65,"body":"if he had those symptoms,"},{"startTime":277.65,"endTime":279.06,"body":"but his biomarkers were negative,"},{"startTime":279.06,"endTime":280.637,"body":"then we'd say he has unstable angina."},{"startTime":280.637,"endTime":281.47,"body":"[Dr. Handy] That's right."},{"startTime":281.47,"endTime":283.36,"body":"[Dr. Wiener] Okay, well,"},{"startTime":281.47,"endTime":283.36,"body":"once again, as I mentioned,"},{"startTime":283.36,"endTime":285.88,"body":"we're thrilled to have a guest discussion,"},{"startTime":285.88,"endTime":287.81,"body":"Dr. Joseph Loscalzo here with us."},{"startTime":287.81,"endTime":290.26,"body":"So let's start the"},{"startTime":287.81,"endTime":290.26,"body":"discussion with Dr. Loscalzo."},{"startTime":290.26,"endTime":291.55,"body":"[Dr. Loscalzo] Well, thank"},{"startTime":290.26,"endTime":291.55,"body":"you, Charlie and Cathy,"},{"startTime":291.55,"endTime":293.07,"body":"it's wonderful to be back with you,"},{"startTime":293.07,"endTime":295.0,"body":"I really enjoy these sessions."},{"startTime":295.0,"endTime":297.325,"body":"[Dr. Handy] So making the"},{"startTime":295.0,"endTime":297.325,"body":"diagnosis of acute coronary"},{"startTime":297.325,"endTime":302.32,"body":"syndrome in 2021 still depends"},{"startTime":297.325,"endTime":302.32,"body":"on the history and the EKG."},{"startTime":302.32,"endTime":305.98,"body":"Biomarkers so far have really"},{"startTime":302.32,"endTime":305.98,"body":"not completely replaced that."},{"startTime":305.98,"endTime":309.15,"body":"So where are we with biomarkers"},{"startTime":305.98,"endTime":309.15,"body":"for coronary syndromes and"},{"startTime":309.15,"endTime":311.47,"body":"how do you see the diagnosis"},{"startTime":309.15,"endTime":311.47,"body":"of acute coronary syndrome"},{"startTime":311.47,"endTime":313.95,"body":"evolving in the next 5-10 years?"},{"startTime":313.95,"endTime":315.36,"body":"[Dr. Loscalzo] Thank you"},{"startTime":313.95,"endTime":315.36,"body":"for that question, Cathy,"},{"startTime":315.36,"endTime":317.43,"body":"I guess the first point"},{"startTime":315.36,"endTime":317.43,"body":"that I would make is that"},{"startTime":317.43,"endTime":320.1,"body":"it's fairly straightforward,"},{"startTime":317.43,"endTime":320.1,"body":"not invariably"},{"startTime":320.1,"endTime":324.03,"body":"but generally to distinguish"},{"startTime":320.1,"endTime":324.03,"body":"a STEMI from a non-STEMI,"},{"startTime":324.03,"endTime":327.82,"body":"which could either be an"},{"startTime":324.03,"endTime":327.82,"body":"NSTEMI or unstable angina."},{"startTime":327.82,"endTime":330.58,"body":"Distinguishing an NSTEMI"},{"startTime":327.82,"endTime":330.58,"body":"from unstable angina"},{"startTime":330.58,"endTime":333.44,"body":"on the other hand is more"},{"startTime":330.58,"endTime":333.44,"body":"challenging but it's important"},{"startTime":333.44,"endTime":336.36,"body":"because making that decision then leads to"},{"startTime":336.36,"endTime":339.32,"body":"direct management decisions"},{"startTime":336.36,"endTime":339.32,"body":"that are different for the two"},{"startTime":339.32,"endTime":341.73,"body":"causes of an acute coronary syndrome."},{"startTime":341.73,"endTime":343.82,"body":"Now, as you say, biomarkers have evolved,"},{"startTime":343.82,"endTime":345.35,"body":"but not gotten to the point that"},{"startTime":345.35,"endTime":347.65,"body":"we could consider them foolproof."},{"startTime":347.65,"endTime":350.09,"body":"The most useful biomarkers these days,"},{"startTime":350.09,"endTime":353.31,"body":"of course, are troponins, troponin T or I."},{"startTime":353.31,"endTime":356.71,"body":"Now we're in our fifth"},{"startTime":353.31,"endTime":356.71,"body":"generation of troponin assays,"},{"startTime":356.71,"endTime":358.7,"body":"they've become more and more sensitive,"},{"startTime":358.7,"endTime":361.89,"body":"and as a consequence, they've"},{"startTime":358.7,"endTime":361.89,"body":"lost a bit of specificity,"},{"startTime":361.89,"endTime":364.64,"body":"such that we can now detect"},{"startTime":361.89,"endTime":364.64,"body":"low levels of circulating"},{"startTime":364.64,"endTime":368.99,"body":"troponin in more than 50% of"},{"startTime":364.64,"endTime":368.99,"body":"normal healthy individuals."},{"startTime":368.99,"endTime":372.04,"body":"So as a consequence of"},{"startTime":368.99,"endTime":372.04,"body":"that improved sensitivity"},{"startTime":372.04,"endTime":374.65,"body":"with a potential for loss of specificity,"},{"startTime":374.65,"endTime":377.77,"body":"now the European Society of"},{"startTime":374.65,"endTime":377.77,"body":"Cardiology and other groups have"},{"startTime":377.77,"endTime":381.73,"body":"worked out cutoffs based on"},{"startTime":377.77,"endTime":381.73,"body":"measurements in populations with"},{"startTime":381.73,"endTime":385.55,"body":"definable diagnoses of"},{"startTime":381.73,"endTime":385.55,"body":"acute coronary syndromes."},{"startTime":385.55,"endTime":387.22,"body":"So in the initial measurement,"},{"startTime":387.22,"endTime":390.61,"body":"one can comfortably rule out"},{"startTime":387.22,"endTime":390.61,"body":"acute myocardial infarction"},{"startTime":390.61,"endTime":394.16,"body":"if the troponin is less than 5 ng/mL,"},{"startTime":394.16,"endTime":396.8,"body":"if it's greater than 52 ng/mL"},{"startTime":396.8,"endTime":398.88,"body":"with the latest generation assay,"},{"startTime":398.88,"endTime":402.49,"body":"one can rule in comfortably"},{"startTime":398.88,"endTime":402.49,"body":"myocardial infarction."},{"startTime":402.49,"endTime":405.41,"body":"After the first hour when"},{"startTime":402.49,"endTime":405.41,"body":"a second set is sent,"},{"startTime":405.41,"endTime":409.564,"body":"if the level of troponin"},{"startTime":405.41,"endTime":409.564,"body":"remains less than 3 ng/mL,"},{"startTime":409.564,"endTime":412.36,"body":"that's consistent with"},{"startTime":409.564,"endTime":412.36,"body":"a rule-out diagnosis,"},{"startTime":412.36,"endTime":416.57,"body":"but now if it is equal"},{"startTime":412.36,"endTime":416.57,"body":"to or exceeds 5 ng/mL,"},{"startTime":416.57,"endTime":417.92,"body":"the change in troponin,"},{"startTime":417.92,"endTime":420.71,"body":"that's consistent with"},{"startTime":417.92,"endTime":420.71,"body":"a rule-in diagnosis."},{"startTime":420.71,"endTime":423.24,"body":"So troponin is an invaluable biomarker,"},{"startTime":423.24,"endTime":424.97,"body":"but it comes with some provisos"},{"startTime":424.97,"endTime":427.55,"body":"not the least of which"},{"startTime":424.97,"endTime":427.55,"body":"is the sensitivity issue,"},{"startTime":427.55,"endTime":429.25,"body":"but also in context,"},{"startTime":429.25,"endTime":431.76,"body":"it's often difficult"},{"startTime":429.25,"endTime":431.76,"body":"to interpret troponins."},{"startTime":431.76,"endTime":434.27,"body":"So for example, in patients"},{"startTime":431.76,"endTime":434.27,"body":"with chronic kidney disease,"},{"startTime":434.27,"endTime":435.87,"body":"especially those in dialysis,"},{"startTime":435.87,"endTime":438.47,"body":"there is increased circulating levels"},{"startTime":438.47,"endTime":440.56,"body":"of troponin that persist,"},{"startTime":440.56,"endTime":443.428,"body":"and one needs to know what"},{"startTime":440.56,"endTime":443.428,"body":"the baseline level might be"},{"startTime":443.428,"endTime":446.773,"body":"in a patient before interpreting"},{"startTime":443.428,"endTime":446.773,"body":"a change in that level"},{"startTime":446.773,"endTime":450.24,"body":"in a patient with such"},{"startTime":446.773,"endTime":450.24,"body":"severe renal disease."},{"startTime":450.24,"endTime":452.89,"body":"But there are alternate biomarkers"},{"startTime":450.24,"endTime":452.89,"body":"that are now making their"},{"startTime":452.89,"endTime":456.22,"body":"way through evaluation,"},{"startTime":452.89,"endTime":456.22,"body":"one of course is NT-proBNP,"},{"startTime":456.22,"endTime":457.78,"body":"which has been used for a while."},{"startTime":457.78,"endTime":461.03,"body":"Of course, it is another"},{"startTime":457.78,"endTime":461.03,"body":"measure of stress,"},{"startTime":461.03,"endTime":465.29,"body":"BNP or NT-proBNP, its"},{"startTime":461.03,"endTime":465.29,"body":"precursor is released"},{"startTime":465.29,"endTime":467.93,"body":"from a stressed"},{"startTime":465.29,"endTime":467.93,"body":"cardiomyocyte as might occur"},{"startTime":467.93,"endTime":470.72,"body":"in patients with ischemic disease."},{"startTime":470.72,"endTime":474.52,"body":"Galectin-3 is a molecule"},{"startTime":470.72,"endTime":474.52,"body":"that's secreted by activated"},{"startTime":474.52,"endTime":477.07,"body":"macrophages, so with plaque activation"},{"startTime":477.07,"endTime":482.07,"body":"it may be a good marker for"},{"startTime":477.07,"endTime":482.07,"body":"an acute coronary event."},{"startTime":482.07,"endTime":486.75,"body":"GDF-15 which is growth or"},{"startTime":482.07,"endTime":486.75,"body":"differentiation factor 15"},{"startTime":486.75,"endTime":491.03,"body":"is another stress induced"},{"startTime":486.75,"endTime":491.03,"body":"cytokine that is being evaluated,"},{"startTime":491.03,"endTime":493.82,"body":"and copeptin, which together with troponin"},{"startTime":493.82,"endTime":495.75,"body":"can very clearly identify"},{"startTime":495.75,"endTime":498.64,"body":"high-risk individuals"},{"startTime":495.75,"endTime":498.64,"body":"with stress induced injury"},{"startTime":498.64,"endTime":502.37,"body":"like Takotsubo, is another"},{"startTime":498.64,"endTime":502.37,"body":"marker that's evolving."},{"startTime":502.37,"endTime":505.02,"body":"But I would say to answer"},{"startTime":502.37,"endTime":505.02,"body":"your question more succinctly,"},{"startTime":505.02,"endTime":508.19,"body":"I'm not always succinct,"},{"startTime":505.02,"endTime":508.19,"body":"I apologize, is that"},{"startTime":508.19,"endTime":511.71,"body":"to have a really meaningful"},{"startTime":508.19,"endTime":511.71,"body":"signature of biomarkers"},{"startTime":511.71,"endTime":515.09,"body":"in a sort of weighted equation"},{"startTime":511.71,"endTime":515.09,"body":"is really what we should move"},{"startTime":515.09,"endTime":517.87,"body":"toward and over time,"},{"startTime":515.09,"endTime":517.87,"body":"I believe, we'll get there."},{"startTime":517.87,"endTime":519.632,"body":"[Dr. Wiener] In light of that,"},{"startTime":517.87,"endTime":519.632,"body":"Joe, just the markers you"},{"startTime":519.632,"endTime":523.1,"body":"just mentioned, when do you"},{"startTime":519.632,"endTime":523.1,"body":"foresee that they may be ready"},{"startTime":523.1,"endTime":525.46,"body":"for prime time or common usage?"},{"startTime":525.46,"endTime":526.847,"body":"[Dr. Loscalzo] Well, I think"},{"startTime":525.46,"endTime":526.847,"body":"a couple of them are actually"},{"startTime":526.847,"endTime":529.01,"body":"making their way to"},{"startTime":526.847,"endTime":529.01,"body":"prime time pretty quickly"},{"startTime":529.01,"endTime":530.12,"body":"in the next couple of years,"},{"startTime":530.12,"endTime":533.76,"body":"like Galectin-3 or GDF-15 as an example."},{"startTime":533.76,"endTime":535.728,"body":"[Dr. Wiener] All right,"},{"startTime":533.76,"endTime":535.728,"body":"Cathy well that's going to be"},{"startTime":535.728,"endTime":538.04,"body":"a challenge for future podclass, I guess."},{"startTime":538.04,"endTime":540.253,"body":"Joe, assuming this"},{"startTime":538.04,"endTime":540.253,"body":"patient was on appropriate"},{"startTime":540.253,"endTime":543.197,"body":"medical therapy for his"},{"startTime":540.253,"endTime":543.197,"body":"hypertension and his hyperlipidemia,"},{"startTime":543.197,"endTime":545.323,"body":"what other preventive"},{"startTime":543.197,"endTime":545.323,"body":"measures can be taken?"},{"startTime":545.323,"endTime":548.33,"body":"It seems like we're always"},{"startTime":545.323,"endTime":548.33,"body":"counseling our patients on"},{"startTime":548.33,"endTime":551.69,"body":"lifestyle modification"},{"startTime":548.33,"endTime":551.69,"body":"and diet and exercise,"},{"startTime":551.69,"endTime":554.2,"body":"but success in achieving"},{"startTime":551.69,"endTime":554.2,"body":"those is really hard."},{"startTime":554.2,"endTime":556.79,"body":"Do you have any tips for us"},{"startTime":554.2,"endTime":556.79,"body":"or any other ancillary things"},{"startTime":556.79,"endTime":558.26,"body":"that we should be thinking about?"},{"startTime":558.26,"endTime":560.74,"body":"[Dr. Loscalzo] Well, I think"},{"startTime":558.26,"endTime":560.74,"body":"the key is not to give up."},{"startTime":560.74,"endTime":563.59,"body":"We shouldn't give up as the"},{"startTime":560.74,"endTime":563.59,"body":"patient's physician in bringing"},{"startTime":563.59,"endTime":566.16,"body":"these issues to the patient's"},{"startTime":563.59,"endTime":566.16,"body":"attention and the patients"},{"startTime":566.16,"endTime":568.68,"body":"shouldn't give up if"},{"startTime":566.16,"endTime":568.68,"body":"they attempt and fail."},{"startTime":568.68,"endTime":571.5,"body":"As you know, it takes on"},{"startTime":568.68,"endTime":571.5,"body":"average about seven times"},{"startTime":571.5,"endTime":573.64,"body":"before someone actually stops smoking"},{"startTime":573.64,"endTime":575.29,"body":"who has an intention to do so."},{"startTime":575.29,"endTime":577.36,"body":"It's a little easier with some"},{"startTime":575.29,"endTime":577.36,"body":"of the current medications,"},{"startTime":577.36,"endTime":579.83,"body":"but it still takes a number"},{"startTime":577.36,"endTime":579.83,"body":"of efforts before you get to"},{"startTime":579.83,"endTime":583.08,"body":"a real smoke-free lifestyle"},{"startTime":579.83,"endTime":583.08,"body":"in someone who smoked"},{"startTime":583.08,"endTime":585.61,"body":"for much of their adulthood."},{"startTime":585.61,"endTime":587.21,"body":"Similarly for weight management,"},{"startTime":587.21,"endTime":590.45,"body":"which seems literally"},{"startTime":587.21,"endTime":590.45,"body":"impossible in many cases,"},{"startTime":590.45,"endTime":594.2,"body":"one needs to encourage"},{"startTime":590.45,"endTime":594.2,"body":"patients, celebrate even modest"},{"startTime":594.2,"endTime":595.42,"body":"improvements in their weight,"},{"startTime":595.42,"endTime":598.56,"body":"continue to bring to their"},{"startTime":595.42,"endTime":598.56,"body":"attention ways to adjust their"},{"startTime":598.56,"endTime":601.67,"body":"eating habits and the stresses"},{"startTime":598.56,"endTime":601.67,"body":"that might lead to them."},{"startTime":601.67,"endTime":603.97,"body":"Again, there are new drugs on the horizon,"},{"startTime":603.97,"endTime":605.6,"body":"which really do seem to make a difference,"},{"startTime":605.6,"endTime":607.37,"body":"whether they will make a persistent,"},{"startTime":607.37,"endTime":610.18,"body":"durable difference or"},{"startTime":607.37,"endTime":610.18,"body":"not, remains to be seen."},{"startTime":610.18,"endTime":611.46,"body":"So from my perspective,"},{"startTime":611.46,"endTime":614.533,"body":"I always try to take as"},{"startTime":611.46,"endTime":614.533,"body":"positive an attitude as I can"},{"startTime":614.533,"endTime":617.57,"body":"in discussing these kinds"},{"startTime":614.533,"endTime":617.57,"body":"of issues with my patient."},{"startTime":617.57,"endTime":619.685,"body":"I also think that cardiac"},{"startTime":617.57,"endTime":619.685,"body":"rehabilitation is also"},{"startTime":619.685,"endTime":621.79,"body":"an important element post infarct,"},{"startTime":621.79,"endTime":624.64,"body":"or post acute coronary"},{"startTime":621.79,"endTime":624.64,"body":"syndrome or intervention."},{"startTime":624.64,"endTime":627.1,"body":"It may not always seem so to the patient,"},{"startTime":627.1,"endTime":628.69,"body":"especially if they feel reasonably well,"},{"startTime":628.69,"endTime":632.34,"body":"but they can begin to experience"},{"startTime":628.69,"endTime":632.34,"body":"through the rehabilitation"},{"startTime":632.34,"endTime":634.78,"body":"program and their"},{"startTime":632.34,"endTime":634.78,"body":"interactions with other folks"},{"startTime":634.78,"endTime":636.34,"body":"who are going through the same program,"},{"startTime":636.34,"endTime":640.05,"body":"begin to experience some of"},{"startTime":636.34,"endTime":640.05,"body":"the strategies that others have"},{"startTime":640.05,"endTime":644.1,"body":"used with some success at"},{"startTime":640.05,"endTime":644.1,"body":"improving these lifestyle issues."},{"startTime":644.1,"endTime":645.72,"body":"And of course, one can never say too much"},{"startTime":645.72,"endTime":647.36,"body":"about a regular exercise prescription,"},{"startTime":647.36,"endTime":650.09,"body":"even if it's just armchair stretching."},{"startTime":650.09,"endTime":651.82,"body":"[Dr. Handy] And as a vascular biologist,"},{"startTime":651.82,"endTime":653.84,"body":"do you have any thoughts on the mechanisms"},{"startTime":653.84,"endTime":655.42,"body":"that we'll be hearing about soon?"},{"startTime":655.42,"endTime":656.54,"body":"[Dr. Loscalzo] I have"},{"startTime":655.42,"endTime":656.54,"body":"lots of thoughts in that,"},{"startTime":656.54,"endTime":657.881,"body":"but I only have a minute or so-"},{"startTime":657.881,"endTime":658.998,"body":"[Dr. Handy and Dr. Wiener chuckle]"},{"startTime":658.998,"endTime":661.65,"body":"[Dr. Loscalzo] -so I'll"},{"startTime":658.998,"endTime":661.65,"body":"give you sort of a taste of"},{"startTime":661.65,"endTime":663.08,"body":"some of the things that interest me."},{"startTime":663.08,"endTime":665.01,"body":"The first is that we're"},{"startTime":663.08,"endTime":665.01,"body":"moving in a direction"},{"startTime":665.01,"endTime":667.5,"body":"of trying to define what people call"},{"startTime":667.5,"endTime":671.15,"body":"patient-based endotypes or endophenotypes,"},{"startTime":671.15,"endTime":674.49,"body":"and these are really"},{"startTime":671.15,"endTime":674.49,"body":"determinants of fundamental"},{"startTime":674.49,"endTime":677.28,"body":"pathological mechanisms"},{"startTime":674.49,"endTime":677.28,"body":"that underlie all diseases"},{"startTime":677.28,"endTime":680.6,"body":"such as inflammation,"},{"startTime":677.28,"endTime":680.6,"body":"thrombosis, fibrosis,"},{"startTime":680.6,"endTime":683.55,"body":"so that you can imagine a"},{"startTime":680.6,"endTime":683.55,"body":"day when one can identify"},{"startTime":683.55,"endTime":686.77,"body":"a patient as being very strongly"},{"startTime":683.55,"endTime":686.77,"body":"pro-inflammatory based on"},{"startTime":686.77,"endTime":690.54,"body":"some signature or"},{"startTime":686.77,"endTime":690.54,"body":"prothrombotic in which case,"},{"startTime":690.54,"endTime":691.89,"body":"based on those signatures,"},{"startTime":691.89,"endTime":694.83,"body":"one might approach a therapeutic strategy,"},{"startTime":694.83,"endTime":697.3,"body":"both acutely as well as preventively"},{"startTime":697.3,"endTime":699.57,"body":"from a more personalized basis."},{"startTime":699.57,"endTime":700.92,"body":"For example, in the case of"},{"startTime":700.92,"endTime":703.2,"body":"an enhanced inflammatory response,"},{"startTime":703.2,"endTime":706.64,"body":"one might explore with the"},{"startTime":703.2,"endTime":706.64,"body":"appropriate biomarker signatures"},{"startTime":706.64,"endTime":709.32,"body":"pathways that govern"},{"startTime":706.64,"endTime":709.32,"body":"inflammation in that patient,"},{"startTime":709.32,"endTime":713.22,"body":"such as senescence associated"},{"startTime":709.32,"endTime":713.22,"body":"secretory phenotypes,"},{"startTime":713.22,"endTime":716.48,"body":"and their downstream mediators"},{"startTime":713.22,"endTime":716.48,"body":"like interleukin-1 beta,"},{"startTime":716.48,"endTime":719.81,"body":"or alpha-7 nicotinic"},{"startTime":716.48,"endTime":719.81,"body":"acetylcholine receptor"},{"startTime":719.81,"endTime":723.77,"body":"dependent activation, or"},{"startTime":719.81,"endTime":723.77,"body":"the NLRP inflammasome,"},{"startTime":723.77,"endTime":725.67,"body":"or altered NAD metabolism"},{"startTime":725.67,"endTime":728.08,"body":"and its consequences for inflammation."},{"startTime":728.08,"endTime":730.09,"body":"Those are some of the"},{"startTime":728.08,"endTime":730.09,"body":"areas that are blossoming"},{"startTime":730.09,"endTime":734.29,"body":"as potential pathological"},{"startTime":730.09,"endTime":734.29,"body":"and pathobiological foci."},{"startTime":734.29,"endTime":737.09,"body":"And I'll just make one last"},{"startTime":734.29,"endTime":737.09,"body":"point to this question, Cathy,"},{"startTime":737.09,"endTime":739.81,"body":"that there's growing emphasis"},{"startTime":737.09,"endTime":739.81,"body":"and recognition of the links"},{"startTime":739.81,"endTime":743.7,"body":"between inflammation and"},{"startTime":739.81,"endTime":743.7,"body":"metabolism in the blood vessel wall"},{"startTime":743.7,"endTime":746.13,"body":"and its consequences for vascular function"},{"startTime":746.13,"endTime":747.89,"body":"and therapeutic intervention."},{"startTime":747.89,"endTime":749.71,"body":"For example, most people don't realize"},{"startTime":749.71,"endTime":752.58,"body":"that the healthy endothelium"},{"startTime":749.71,"endTime":752.58,"body":"gets most of its ATP"},{"startTime":752.58,"endTime":756.06,"body":"from glycolysis, not"},{"startTime":752.58,"endTime":756.06,"body":"oxidative phosphorylation,"},{"startTime":756.06,"endTime":759.06,"body":"even in a normal, healthy"},{"startTime":756.06,"endTime":759.06,"body":"oxygen rich environment."},{"startTime":759.06,"endTime":762.84,"body":"Endothelial dysfunction modulates"},{"startTime":759.06,"endTime":762.84,"body":"this glycolytic phenotype,"},{"startTime":762.84,"endTime":764.14,"body":"and that is associated with"},{"startTime":764.14,"endTime":766.58,"body":"enhanced endothelial inflammation,"},{"startTime":766.58,"endTime":769.22,"body":"adhesion molecule expression, for example."},{"startTime":769.22,"endTime":771.62,"body":"So that kind of pathobiology begins"},{"startTime":771.62,"endTime":773.47,"body":"to offer novel therapeutic targets"},{"startTime":773.47,"endTime":775.49,"body":"that we haven't thought about previously."},{"startTime":775.49,"endTime":777.72,"body":"[Dr. Wiener] Wow, that's"},{"startTime":775.49,"endTime":777.72,"body":"just another a great example"},{"startTime":777.72,"endTime":780.13,"body":"of how precision medicine"},{"startTime":777.72,"endTime":780.13,"body":"is going to become"},{"startTime":780.13,"endTime":782.22,"body":"more precise as we move forward"},{"startTime":782.22,"endTime":785.49,"body":"and our translational research"},{"startTime":782.22,"endTime":785.49,"body":"gets in from the bench"},{"startTime":785.49,"endTime":787.993,"body":"to the bedside, that's"},{"startTime":785.49,"endTime":787.993,"body":"great, that's really cool."},{"startTime":787.993,"endTime":789.09,"body":"[Dr. Loscalzo] Thank you."},{"startTime":789.09,"endTime":790.67,"body":"[Dr. Handy] Joe, it's always"},{"startTime":789.09,"endTime":790.67,"body":"a pleasure having you here,"},{"startTime":790.67,"endTime":793.32,"body":"thank you so much, and"},{"startTime":790.67,"endTime":793.32,"body":"for those listening,"},{"startTime":793.32,"endTime":794.22,"body":"if you want to learn more,"},{"startTime":794.22,"endTime":796.48,"body":"you can read about this"},{"startTime":794.22,"endTime":796.48,"body":"in Harrison's chapter"},{"startTime":796.48,"endTime":798.15,"body":"on acute coronary syndromes."},{"startTime":798.15,"endTime":802.4,"body":"[outro music]"},{"startTime":802.4,"endTime":805.24,"body":"[Mr. Shanahan] This is Jim"},{"startTime":802.4,"endTime":805.24,"body":"Shanahan, publisher at McGraw Hill."},{"startTime":805.24,"endTime":806.923,"body":"Harrison's Podclass is brought to you"},{"startTime":806.923,"endTime":808.86,"body":"by McGraw Hill's Access Medicine,"},{"startTime":808.86,"endTime":811.84,"body":"the online medical resource"},{"startTime":808.86,"endTime":811.84,"body":"that delivers the latest trusted"},{"startTime":811.84,"endTime":814.16,"body":"content from the best minds in medicine."},{"startTime":814.16,"endTime":816.723,"body":"Go to accessmedicine.com to learn more."}]}