COVID-19: Cardiovascular Complications

Cardiovascular complications are both a relatively common and clinically significant complication in provocations representing a substantial mortality risk. It is become very clear that serious pre existing conditions are a major complication, while with regard to the severity of COVID-19. Both hypertension and cardiovascular disease are pre existing conditions that are clearly put patients at a risk of mortality. And this is particularly true in patients greater than 65 years of age. Why are cardiologists so concerned about COVID-19? Well, you can see at first. As I mentioned, hypertension and coronary heart disease have present. Are both significant risk factors for mortality in COVID-19 patients? For example, 23% of survivors had hypertension as compared to 48% in non survivors. And 1% of survivors had coronary heart disease as compared to 24% in non survivors. Furthermore, an admission only 1% of survivors had proponent levels greater than the 99 percentile as compared to 48% in non survivals. The outcomes in these patients was also an issue. Cardiovascular complications, both heart failure and acute cardiac injury are common outcomes in COVID-19 patients. Sorry, Kobe to significantly finds through the transmembrane ace two receptor present on various tissue types, including lung, kidney, gut. An heart leading to information and multi organ failure. Infection of India. Filial cells in the Kappel Aries is of particular importance Becausw. It could lead to severe microvascular and macrovascular dysfunction. In addition, immune over reactivity can destabilize plaques. And in some cases even cause DIC and explain the development of acute coronary syndrome, including myocardial infarction. Infection of the respiratory tract is manifested by the progression of systemic and information, an immune cell overactivation leading to cytokine storm, resulting in increased levels of side effects. Subsequently, it is possible that activated T cells. And macrophages. May infiltrate infected myocardium resulting in the development of myocarditis and severe cardiac damage including heart failure. In a similar way, viral invasion may cause direct cardiac myocyte damage, leading tomorrow cardial dysfunction and contribute to the development of severe cardiac arrhythmia. There are several possible mechanisms for the elevations that are seen in COVID-19 patients. High levels of side clouds or satisfying storm appears to be a leading candidate for many of the serious complications seen in covid patients. Side accounts can cause myocarditis by direct cardiac injury resulting in elevated ropponen levels. Cytokinins can also cause endothelial dysfunction and micro energy opathy. Which can ultimately result in inflammation and plaque instability and rupture, which is a type one. Am I hypoxia? An infection can also cause an oxygen supply and demand imbalance, which of course is a Type 2 am I. Endothelial dysfunction and plaque instability put on only cause a mark cardial infarction but also lead to severe coagulations dysfunction with a high D dimer levels as seen in disseminated intravascular coagulations. Elevate your opponent levels during hospitalization. Have been shown to be associated with increased mortality. Higher mortality rates are clearly associated with higher trip onen levels, reaching over 91% mortality. One trip, onen levels greater than 0.78 are seen. In this particular study, the obvious entered proponent I Ultra assay was used. In a separate study, similar results were obtained on the left side. Mortality rates were very high in patients with pre existing cardiovascular disease and elevated component levels. On the right side, the data shows significantly higher to opponent levels among non survivors versus survivors. In addition, height ropponen levels were seen within the Non Survivor Group as the severity of disease increased. Trip onen levels are not only increased between survivors and non survivors, but showed a steady increase increase within the non Survivor Group during their disease progression. Grace is a murder analysis of eight studies with over 400 patients without cardiac injury, and over 1100 patients. With cardiac injury, the results clearly show. That overall, there was an 8 fold risk of mortality between these two groups. Here is a case study to illustrate that not all elevated proponent levels, even very high levels, necessarily means that the patient has or had amarra cardial infarction. On initial assessment, the patient was a 37 year old male presenting with chest pain, disneya, and diarrhea. For three days, the ECG showed an St elevation. With triponey greater than 10,000 out of grams per liter. Coronary angiography revealed no stenosis on further investigation by echocardiography showed an ejection fraction of 27%. X Ray showed no left sided cardiac enlargement and chest CT indicated pulmonary infection. Sputum was Cyrus Coby 2 positive by PCR. The diagnosis in his patient was determined to be COVID-19 infection with full minute mile cardio, myocarditis and cardiogenic shock. The patient was treated with glucocorticoids, an immunoglobulin. On follow up. One week later, the Chest X Ray was essentially normal with normal with a normal ejection fraction of 66% cardiac trip onen at that time was still elevated, but much lower had 229 of grams per liter. The previous slide was a case case study showing that not all STL elevations seen in patients necessarily mean myocardial infarction. In this small study, 18 COVID-19 patients. Who had St elevations? Wow, eight of the 18 had an MI or 45%. 10 of the 18 or 55% did not show in MI. And were diagnosed with non cardiac myocardial injury based upon either the lack of extre obstructive coronary artery disease on angiogram or the lack of regional wall motion abnormality on echocardiogram. There are a number of potential causes of myocardial injury in COVID-19 patients that may or may not be type one MI, but may have an elevated proponent. Here is a quote from an interventional cardiologist in New York City. We now we've now instituted a protocol where a fellow with an ultrasound is going down to the Ed and assessing for global dysfunction. To avoid bringing the patient into the Cath lab. And exposing the entire team only to find that he has pericarditis, mychart card, ritis, or something other than acute carrier coronary syndrome. So in summary, patients with COVID-19. Elevated and or rising cardiac component levels may be seen in some patients with fatal disease. Elevated trip onen levels may be a risk factor for COVID-19 mortality. A history of cardiovascular disease further adds to the mortality risk. There may be possible reasons for trip onen elevations in COVID-19 patients. It is not necessary necessarily a type 1M I. They have been case reports of patients presenting to the hospital with classic symptoms of St Elevated MI, who in fact have myocarditis likely caused by COVID-19. In one institution, serving a community with high prevalence of a COVID-19, patients presented with presenting with classic STEMI symptoms. Are screened with ultrasound to exclude myocarditis before cardiac Cath is considered. Thank you for your time.

Some underlying conditions in hospitalized SIEMENS Cardiac injury is associated with mortality, need for ICU care, Potential mechanisms of SARS-CoV-2 infection Elevated troponin levels may be a prognostic marker of Why are cardiologists concerned about COVID-19? ST-elevations in COVID-19 patients, do not necessarily Cardiac troponin elevations in severely ill COVID-19 patients: Case Report: Fulminant myocarditis secondary to COVID-19, COVID-19 patients with elevated cardiac troponin may be at Possible mechanisms explaining troponin elevation Hypotheses and best practice sharing regarding cTn elevations Section Summary Healthineers Healthineers • SIEMENS .. SIEMENS COVID-19 Patients and severity of disease in patients with COVID-19 on the cardiovascular system in patients with COVID-19 mortality high risk of mortality "disguised" as myocardial infarction irdicte myocardial infarction myocardial infarction. irdicate myocardial infarction Direicte myocardial inferction indicate myocardial infarction Potential prognostic factor Direct myocardial infection irdictue myocardial infarction in COVID-19 patients — may not be Type I MI "ndisgue myocardial infarction myocardial inferction. Mortality 8% Healthineers • Many non-survivors had increasing cTn Patients with elevated cTn, have higher mortality Cytokines DIC = Disseminated Intravascular Coagulation SARS-CoV-2 Initial assessment In patients with COVID-19, elevated and/or rising cardiac troponin (cTn) levels may be seen in some cTnI in hospitalized COVID-19 patients in Wuhan, China Elevated troponin I during hospitalization is associated with increased mortality Survivor (n=137) Non-survivor (n=54) Survivor Total (n: Total (n=18) 10 18) 11 15 Non-survivor (n=54) Myocarditis Myocardial Myocardials Non-coronary P-value Cardiac Injury (-) Cardiac Injury (+) myocardial injury Cardiac Injury (+) Risk Ratio Risk Ratio Type Ml: ARDS Acute Respiratory Distress Syndrome Viral Infection + Infection Viral Infection of We've had to be Rise favored by ACE2 suppression cause both direct and indirect myocardial injury over the course of hospitalization M 37y, chest pain, dyspnea, diarrhea for 3d regardless of CVD history insfarction dysfunction infarction + Infection Acute cardiay injury Acute cardiac injury Cardiac Injury myocardial injury M-H, Random, M-H, Random, patients with fatal disease. atherosclerotic plaque rupture Comorbidities Study or Subgroup Events Total Total Weight Events very careful about 10% 70 (n=10) ECG showed ST segment elevation High concentration in critical patients with COVID-19 95% Cl 95% due to cytokine storm / DIC 25.0 100 p .001 p = .001 <0.0001 choosing patients Mortality of patients at different troponin concentrations. of at different concentration' Hypertension 32 (23%) 26 (48%) 2/9 (22%) 32 (59%) 32 (123%) 4 (20%) 17 (31%) 4 (40%) 26 (48%) 4 (40%) 2/9 (22%) Non-survivors (n=54) cardiac troponin > 10,000 ng/L Son-survivors 91.3 11.3 109 2.3.1 Mortality Elevated cTn levels may be a risk factor for COVID-19 mortality. A history of cardiovascular disease further N=18 COVID-19 patients in New York were ST elevation 2.07 2.0 Vascular cellula- Vascular cellular Hypoxia causing for cath. lab related Cardiovascular disease is a risk 290.6 (n=137) P = .94 Direct vascular infection Direct myocardial infection Viral Infection ARDS Infection ARDS + Infection • Coronary angiography revealed no stenosis Coronary angiography revealed no stenosis Myocarditis p = .94 inflammation Inflarcation inflarcation oxygen supply Diabetes 6/9 (0%) 13 (24%) 4 (20%) 6/9 (67%) 17 (31%) 28 (52%) 1/95 (14%) 1/6 (12%) 16 (12%) 2/9 (22%) 19 (74%) 19 (14%) 17 (31%) 28 (52%) <0.0001 <0.0008 0.024 adds to the mortality risk. found to have ST-segment elevations on ECG. Chen T 2020 4.64[3.00, 7.18] 94 54 18 20.1% interventions... Higher mortality was accompanied by higher troponin factor for COVID-19 mortality Endothelial CVD + elevated cTn: No CVD + elevated cTn: Immunomediated Focal 14 (78%) 1/9 (14%) 28 (52%) 32 (79%) 17 (31%) 32 (23%) 27 (50%) 13 (74%) 6/8 (75%) 32 (73%) 19 (74%) 13 (12%) Endothelial dysfunction, 8 (100%) 16 (12%) 6 (60%) 28 (52%) 8 (100%) 4 (40%) 4 (20%) 16 (12%) 26 (48%) 12 3.0 (1.1 - 5.5) Coronary vessel microemboli: Cardiovascular dysfunction insfarction Mortality 69% concentrations. Coronary heart disease Chronic kidney disease 1/6 (12%) 4 (20%) 1/3 (24%) 13 (24%) 17 (31%) 16 (124%) 6/9 (27%) 13 (124%) 4 (40%) 16 (12%) 13 (74%) 28 (52%) 47 (20%) Myocarditis/ pericarditis: 1.5 1.0051 1.05 134.5 250 22 Further investigations Cytokine Storm injury Plaque rupture and oossible Plaque rupture and possible Involuntary cardiac 6.69[2.61, 17.7] plaque instability Li K 2020 (_9tokine Storm Cytokine storm 65 86 70 40 Oxygen demand Cytokine Storm due to disseminated intravascular Diffuse 4 (40%) 4 (22%) 4 (20%) 4 (40%) 2 (48%) 26 (48%) 4 (20%) Hyper coagulability Hypercoagulability stimulation <0.0001 P = .001 We've now instituted a protocol There may be many possible reasons for cTn elevations in COVID-19 patients it is not necessarily a Type I 10/18 (55%) were diagnosed as non-coronary • Echocardiography: Left ventricular EF 27% Echocardiography: Left ventricular EF 27% coagulation (DIC) COPD 10.94[6.83, 17.52] Luo XM 2020 20 65 303 HS cTnI > 99th percentile 1/95 (1%) No CVD + elevated cTn: No CVD + normal cTn: where a fellow with an ultrasound The thresholds of troponin I selected are based on the reference 200 myocardial infarction. myocardial injury "disgue myocardial infarction myocardial injary X-ray showed enlargement of the heart myocardial injury based on: N=165 N=36 Echocardiography Involuntary cardiac Cardiac cellular injury and Involuntary cardiac complications Mortality 69% Mortality 138% Mortality 38% Oxygen demand (28ng/L) Shi S 2020 11.40[6.66, 19.531 40 86 82 150 334 11.6% is going down to the ER and assessing Cancer value, <0.006 ng/mL is the lowest value in our hospital laboratory, 0.347 0.0247 0.024 9.3% stimulation stimulation necros•s Chest CT indicated pulmonary infection Myocardials Myocarditis p -.96 p: .96 36.2 134.5 Microangiopathy 350 13 Low ejection fraction 9/ 17 (53%) 7/8 (88%) 4 (40%) 26 (48%) 6/9 (27%) 4/9 (22%) 1/9 (12%) 1/9 (14%) 28 (52%) 13 (24%) 6/9 (67%) 2/9 (22%) 32 (29%) 26 (42%) 16 (123%) 1/9 (1%) 16 (12%) 6/9 (07%) Myocarditis for global dysfunction... to avoid 0.006-0.04 ng/mL is the biological reference interval, >0.04 ng/mL 5.25 [2.90, 9.501 • Sputum: SARS-CoV-2 positive Sputum: SARS-CoV-2 positive wu c 2020 60 82 22 15 18 126 17.2% There have been case reports of patients presenting to the hospital with classic symptoms of STEMI, Chronic kidney disease dysfunction + Infection 0.024 Hypoxia causing No CVD + normal cTn: CVD + normal No CVD + normal CTn: Right ventricular stress: Catecholamine-induced IRD._ Viral Infection + Infection Cytokine storm Cytokine Storm Cardiac output myocardial injury Cardiac Injury 10.0051 0.347 0.0571 bringing the patient to the cath. lab, indicating cardiac injury, and >0.78 ng/mL suggesting myocardial N=30 P = .81 .71 I. Lack of obstructive coronary artery disease oxygen supply Elevated cTn at admission may Mortality 83% who in fact have myocarditis likely caused by COVID-19. COVID-19 Zhang F 2020 6.08[1.93, 19.131 100% 150% 18 31 19.3% 0.37 19.5% 4.2% 9.3% due to severe pulmonary disease/ 100 150 1.05 myocardial damage: myocardial injury myocardial injur: 10% 10 12 Admission cTnl > 99th percentile 1/95 (14%) 1/95 (1%) 6/9 (0%) 17 (31%) 16 (12%) 0/9 (0%) 23/50 (46%) <0.0008 (and exposing the entire team), only infarction is possible. Diagnosis 6/17 (35%) 6/9 (27%) 0/3 (0%) 6/9 (67%) 1/9 (1%) 6/6 (100%) 28 (52%) 6/8 (75%) 32 (79%) 6 (60%) 2/9 (22%) 27 (50%) 6/9 (67%) 2/9 (52%) 6/17 (35%) 32 (22%) on angiogram Regional wall motion 22 predict higher risk of death 55.7 edema from adrenal stress response 57.6 55.7 11.1 81.19[11.38, 579.41] 81.19[11.38, 579.411 Zhou 2020 SARS-CoV-2 targets myocardial ACE2 72 31 54 Higher troponin levels in patients with 13 137 Favored by prothrombotic state • In one institution serving a community with a high prevalence of COVID-19, patients presenting to find that he has pericarditis, Direicte myocardial inferction myocardial inferction myocardial infarction. Direct myocardial infection • COVID-19, fulminant myocarditis, cardiogenic shock abnormality Note that increasing cTnl may not be Type I Ml: No CVD + normal cTn: No CVD + normal CTn: Outcomes 100 60 30 40 N=305 N=105 N=165 known CAD High levels Of D-dimer in patients with receptors 91.3 11.1 13 11.3 myocarditis, or something other ADVIA Centaur Tnl-Ultra was used for this study. with classic STEMI symptoms are screened with ultrasound to exclude myocarditis, before cardiac mortality Admission Hospitalization Impending Admission Hospitalization Impendching OR Cardiovascular Obesity Chronic lung disease Coronary heart disease Chronic kidney disease Diabetes Subtotal (95% Cl) Hypertension 424 4.24 4.2% 1126% 100% 109% 7.95[5.12, 12.34] 7.95[5.12, 12.341 • Treatment: glucocorticoid + immunoglobulin • Myocardial ischemia in COVID-19 may be secondary Only clinically suspected cases Inflammation and viral invasion cause plaque COVID-19 death discharge Heart failure 16 (12%) 4 (40%) 6 (0%) 26 (48%) 4 (20%) 28 (52%) 8 (10%) 13 (2%) 27 (50%) 4 (42%) 3.8 than Acute Coronary Syndrome. Cardiovascular complications Son-survivors Non-Survivors catheterization is considered. to hypoxemia/ tachycardia 13 100 2.0 100 60 100 80 80 60 20 .01 18-49 years 50-64 years 265 years NO histological diagnosis in patients with instability and rupture (Type 1 Ml) Disseminated Intravascular Coagulation Total events 259 250 73 <0.0001 < 0.006 0.006 - 0.04 0.04 - 0.78 > 0.78 May 2020 Obstructive coronary 6/9 (67%) 1/9 (1%) 27 (50%) 2/ (50%) 16 (2%) 6/6 (100%) 6/9 (07%) 16 (12%) 2/9 (02%) 6/9 (027%) 0/3 (0%) 6/9 (67%) 13 (24%) 28 (50%) 0/9 (0%) 1/3 (24%) 16 (12%) 1/9 (1%) 27 (50%) 1/9 (14%) 2. Lack of regional wall motion abnormality Type 11 Ml: Viral Infection of Viral infection of myocardial injury are common in non-survivors Follow-up Myocardial 80 13 19 22 myocardial injury Acute cardiac injury myocardiac injury Myocarditis Myocardials Myocardial damage in COVID-19 may be due to 28 (52%) 17 (31%) 32 (59%) 27 (50%) 26 (48%) <0.0008 <0.0001 <0.0051 COVID-19 reported so far Hypoxia and infection cause oxygen is frequently seen in COVID-19 patients Cardiac Troponin I (ng/mL) cardiac troponin > 10,000 ng/L t Heart Failure Risk artery disease on Heart Failure Risk Heart failure Arrhythmias Risk Time since onset Of symptoms to end-point events (days) Survivors Survivors oxygen supply (e.g. hypoxemia) myocardial cells: myocardial injur: Non-Survivors inflammation Infarction Risk Heterogeneity: 0.20; Chi2 17.10, df 6 (P 0.009); 65% Note: Based on data from the COVID-19-Associated Hospitalization Surveillance Network for patients hospitalized in 99 counties supply/demand (Type 2 Ml) • 1 week later: normal X-ray, LVEF 66% Days from Illness Onset Vasculitis-like mechanisms involved? 'cytokine storm'/ catecholamines angiogram anglogram leading to cell lysis/ death demand (e.g. tachycardia) Acute kirdney injury Acute cardiac injury Acute kidney injury Acute cardiay injury myocardial injury 6 (60%) 2/ (0%) 27 (20%) 0/9 (0%) Interventional Cardiologist in New York Test for overall effect: Z 9.24 (p < 0.00001) in 14 States from March 1-3, 2020. cardiac troponin > 10,000 ng/L • Cardiac troponin 220 ng/L N=187 hospitalized patients (Seventh Hospital Of Wuhan City) cTn: cardiac troponin Adapted from: JAMA Cardiol. Published online March 25, 2020. doi:IO.IOOI/jamacardio.2020.09SO CVD history included hypertension, Coronary heart disease and cardiomyopathy Zhou et al. Lancet. 2020. doi: CVD history included hypertension, coronary heart disease and cardiomyopathy Adapted from: JAMA Cardiol. Published online March 25, 2020. doi:IO.IOOI/jamacardio.2020.0950 Adapted from: JAMA Cardiol. Published online March 25, 2020. doi:IffIOOI/jamacardio.2020.09SO 10 100 11 16 12 20 19 13 1.3 50 Adapted from: JAMA Cardiol. doi:IO. 1001/jamacardio.2020.1286 Tersalvi G. et al. Elevated troponin in patients With Coronavirus Disease 2019 This information represents a potential novel clinical utility. Data have not been reviewed by FDA or any other regulatory agency Guo al. 'AMA cardiol. 2020. doi: Guo al. 'AMA cardiol. 2020. doi: 10.1001/jamacardio.2020.101/ Case series from 6 New York area hospitals Xiong et al. Eur Heart J. 2020. doi: 10.1093/eurheartj/ehaa231 Santoso,A, et al., Cardiac injury is associated With mortality and critically ill pneumonia in COVID-19: A meta-analysis, Xiong et al. Eur Heart J. 2020. doi: 10.1093/eurhearti/ehaa231 Guo et al. JAMA cardiol. 2020. doi: 10.1001/jamacardio.2020.1017 N=191 hospitalized patients (Jinyintan hospital and Wuhan Pulmonary hospital) (Modified from Servier Medical Art, licensed under a Creative Common Zhou et al. Lancet. 2020. doi: (COVID•19): possible mechanisms, Journal Of Cardiac Failure (2020), This information represents a potential novel clinical utility. Data have not been reviewed by FDA or any Other regulatory agency American Journal Of Emergency Medicine (2020) Association Of COVID•19 With Myocardial Injury and Mortality. httpsWedhub.ama•assn.orÜjn•learning/audio•player/18361843 source: MMWR. 2020 Apr (early release): 1.7 Association Of COVID-19 With Myocardial Injury and Mortality. Association Of COVID-19 With Myocardial Injury and Mortality. http$//edhub.ama•assn.orÜjn•learning/audio•player/18361843 (COVID-19): possible mechanisms, Journal Of Cardiac Failure (2020), Association Of COVID•19 With Myocardial Injury and Mortality. http$//edhub.ama•assn.orÜjn•learning/audio•player/18361843 source: MMWR. 2020 Apr 8:69 (early release): 1.7 ESC Guidance for the Diagnosis and Management Of CV Disease during the COVID•19 Pandemic •Last updated April 21st 2020 Hu et al. Eur Heart J. 2020 Bangalore al. N Engl J Med. 2020. doi: 10.1056/NEJMc2009020 Attribution 3.0 Generic License. http://smart.servier.com/). Unrestricted O Siemens Healthineers, 2019 Unrestricted O Siemens Healthineers, 2020 20 Unrestrict Healthineers, 2020 10