What’s the connection between elevated troponins and Covid-19?

Elevated cardiac troponins or myocardial injury (defined as troponin levels above the 99th percentile upper reference range) are not uncommon in Covid-19, having been reported in ~10-30% of hospitalized patient and usually observed in the absence of acute coronary syndrome (ACS) (1-4).

 
Elevated troponins have been associated with increased risk of in-hospital mortality in Covid-19. The prevalence of elevated troponins among patients who died was 76% compared to 10% among survivors in 1 Chinese study (3). Another study from China found increasing troponin levels over a 22 day period among those who died while troponin levels remained low in those who survived (5).

 
Risk factors for elevated troponins in Covid-19 include older age, cardiovascular comorbidities (eg, hypertension, coronary heart disease, heart failure), diabetes, chronic obstructive pulmonary disease, chronic renal failure, and the presence of a high inflammatory state, as indicated by elevated inflammatory markers such as C-reactive protein (CRP) (3).

 
Several mechanisms have been proposed to explain elevated troponins in Covid-19, including cytokine-induced myocardial injury, microangiopathy due to prothrombotic state, myocardial infarction (type I due to plaque rupture or type II due to oxygen supply/demand imbalance), and myocarditis either due to direct viral invasion or indirectly through immune-mediated mechanisms (1,2).

 
Patients with Covid-19 and modest troponin elevation with rapid fall in the absence of signs or symptoms of ACS, may have type II myocardial infarction due to demand ischemia, particularly in the setting of coronary disease. In contrast, more protracted elevation of troponins associated with high inflammatory markers such as CRP is suggestive of hyperinflammatory myocardial injury (1).

 

It will be interesting to see if trials of anti-inflammatory agents, such as colchicine and anti-interleukin-I, will have an impact on the troponin levels in Covid-19 patients (1).

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References
1. Cremer PC. SARS-CoV-2 and myocardial injury: few answers, many questions. Clev Clin J Med. Posted April 8, 2020. Doi:10.3949/ccjm.87a.ccc001 https://www.ccjm.org/content/early/2020/05/12/ccjm.87a.ccc001
2. Tersalvi G, Vicenzi M, Calabretta D, et al. Elevated troponin in patients with coronavirus disease 2019:possible mechanisms. J Card Failure 2020; https://pubmed.ncbi.nlm.nih.gov/32315733/
3. Shi S, Qin M, Cai Y, et al. Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019. Eur Heart J 2020. https://pubmed.ncbi.nlm.nih.gov/32391877/
4. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 2020;323:2052-59. https://jamanetwork.com/journals/jama/fullarticle/2765184
5. Zhou F, YU T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-62. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30566-3/fulltext

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

What’s the connection between elevated troponins and Covid-19?

My patient with brain tumor suffered a myocardial infarction (MI) just before having a diagnostic brain surgery. Could the tumor have placed him at higher risk of a coronary event?

Yes! Arterial thromboembolism—just as venous thromboembolism— is more common in patients with cancer.

In a large 2017 epidemiologic study involving patients 66 years of age or older, the 6-month cumulative incidence of MI was nearly 3-fold higher in newly-diagnosed cancer patients compared to controls, with the excess risk resolving by 1 year. 1 These findings were similar to a previous report involving patients with newly-diagnosed cancer, although in that study the overall coronary heart disease risk remained slightly elevated even after 10 years. 2

In addition, the incidence of coronary events and unstable ischemic heart disease during the 2 year period prior to the diagnosis of cancer is 2-fold higher among cancer patients suggesting that ischemic heart disease may be precipitated by occult cancer. 3

The association of cancer and thromboembolic coronary events may be explained through several mechanisms, including development of a prothrombotic or hypercoagulable state through acute phase reactants, abnormal fibrinolytic activity and increased activation of platelets which are also significantly involved in the pathophysiology of acute coronary syndrome (ACS). 4 Coronary artery embolism from cancer-related marantic endocarditis may also occur.5

More specific to our case, primary brain tumors may be associated with a hypercoagulable state through expression of potent procoagulants such as tissue factor and tissue factor containing microparticles, with a subset producing carbon monoxide, another procoagulant. 6

So our patient’s MI prior to his surgery for brain tumor diagnosis might have been more than a pure coincidence!

Bonus Pearl: Did you know that cancer-related prothrombotic state, also known as  “Trousseau’s syndrome” was first described in 1865 by Armand Trousseau, a French physician who diagnosed the same in himself and died of gastric cancer with thrombotic complications just 2 years later? 7,8

References

  1. Navi BB, Reinder AS, Kamel H, et al. Risk of arterial thromboembolism in patients with cancer. JACC 2017;70:926-38. https://www.ncbi.nlm.nih.gov/pubmed/28818202
  2. Zoller B, Ji Jianguang, Sundquist J, et al. Risk of coronary heart disease in patients with cancer: A nationwide follow-up study from Sweden. Eur J Cancer 2012;48:121-128. https://www.ncbi.nlm.nih.gov/pubmed/22023886
  3. Naschitz JE, Yeshurun D, Abrahamson J, et al. Ischemic heart disease precipitated by occult cancer. Cancer 1992;69:2712-20. https://www.ncbi.nlm.nih.gov/pubmed/1571902
  4. Lee EC, Cameron SJ. Cancer and thrombotic risk: the platelet paradigm. Frontiers in Cardiovascular Medicine 2017;4:1-6. https://www.ncbi.nlm.nih.gov/pubmed/29164134
  5. Lee V, Gilbert JD, Byard RW. Marantic endocarditis-A not so benign entity. Journal of Forensic and Legal Medicine 2012;19:312-15. https://www.ncbi.nlm.nih.gov/pubmed/22847046
  6. Nielsen VG, Lemole GM, Matika RW, et al. Brain tumors enhance plasmatic coagulation: the role of hemeoxygenase-1. Anesth Analg 2014;118919-24. https://www.ncbi.nlm.nih.gov/pubmed/24413553
  7. Thalin C, Blomgren B, Mobarrez F, et al. Trousseau’s syndrome, a previously unrecognized condition in acute ischemic stroke associated with myocardial injury. Journal of Investigative Medicine High Impact Case Reports.2014. DOI:10.1177/2324709614539283. https://www.ncbi.nlm.nih.gov/pubmed/26425612
  8. Samuels MA, King MA, Balis U. CPC, Case 31-2002. N Engl J Med 2002;347:1187-94. https://www.nejm.org/doi/pdf/10.1056/NEJMcpc020117?articleTools=true

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My patient with brain tumor suffered a myocardial infarction (MI) just before having a diagnostic brain surgery. Could the tumor have placed him at higher risk of a coronary event?

Why should I pay attention to the augmented vector right (aVR) EKG lead in my patient with chest pain?

Lead aVR is often “neglected” because of its non-adjacent location to other EKG leads (Fig 1) and poor awareness of its potential utility in detecting myocardial ischemia.

In acute coronary syndrome (ACS), ST-elevation (STE) in aVR (≥1mm) with diffuse ST depression in other leads (Fig 2) is usually a sign of severe left main coronary artery (LMCA), proximal left anterior descending (LAD), or 3-vessel coronary disease, and is associated with poor prognosis1-3.  In some patients with LMCA thrombosis, the EKG changes may be non-specific but STE in aVR should still raise suspicion for ischemia1.  Possible mechanisms for STE in aVR include diffuse anterolateral subendocardial ischemia or transmural infarction of the basal portion of the heart. 

The possibility of an anatomical variant of the Purkinje fibers leading to the absence of STE in the anterior leads in some patients with transmural anterior infarction is another reason to pay attention to aVR.

 

Fig 1. Standard EKG limb leads. Note that aVR is “in the fringes”.

ekggreatwork

Fig 2. 35 year old female with ACS due to LMCA spasm. Note STE in aVR with ST segment depression in leads V3-6, I, aVL, II, and aVF  (Courtesy National Library of Medicine)

ekgavr

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References

  1. Kossaify A. ST segment elevation in aVR: clinical syndrome in acute coronary syndrome. Clin Med Insights: Case Reports 2013:6.
  2. Kireyev D, Arkhipov MV, Zador ST. Clinical utility of aVR-the neglected electrocardiographic lead. Ann Noninvasive Electrocardiol 2010;15:175-180.
  3. Wong –CK, Gao W, Stewart RAH, et al. aVR ST elevation: an important but neglected sign in ST elevation acute myocardial infarction. Eur Heart J 2010;31:1845-1853.
  4. De Winter RJ, Verouden NJ, Wellens HJ, et al. A new ECG sign of proximal LAD occlusion. N Engl J Med 2008;359:2071-3.

 

Why should I pay attention to the augmented vector right (aVR) EKG lead in my patient with chest pain?

Which patients outside of ICU setting should be placed on telemetry monitoring in the hospital?

Telemetry monitoring should be used in patients at increased risk of arrhythmias during hospitalization (1). While the American Heart Association provides expert opinion on telemetry for a variety of cardiac conditions (1), a more recent review (2) makes suggestions for common cardiac and non-cardiac diagnoses based on arrhythmia risk.

Telemetry is recommended for patients admitted for implantable cardioverter- defibrillator firing, second or third degree AV block, prolonged QT interval with ventricular arrhythmia, acute heart failure, acute cerebrovascular event,  acute coronary syndrome and massive blood transfusion.

Telemetry may be beneficial in syncope with arrhythmia as a suspected cause, gastrointestinal hemorrhage after endoscopy, atrial arrhythmias on rate or rhythm control therapy, electrolyte imbalance and subacute congestive heart failure.

Telemetry is not generally indicated in chest pain with normal EKG and cardiac markers, COPD exacerbation, PE if the patient is stable and on anticoagulation, and cases requiring minor blood transfusion. 

Contributed by Joome Suh, MD, Boston, MA

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References 

(1) Drew BJ, Califf RM, Funk M, et al. Practice standards for electrocardiographic monitoring in hospital settings: an American Heart Association scientific statement from the Councils on Cardiovascular Nursing, Clinical Cardiology, and Cardiovascular Disease in the Young: endorsed by the International Society of Computerized Electrocardiology and the American Association of Critical-Care Nurses. Circulation 2004;110:2721–46. 

(2) Chen EH and Hollander JE. When do patients need admission to a telemetry bed? The Journal of Emergency Medicine 2007:33(1):53-60.

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Which patients outside of ICU setting should be placed on telemetry monitoring in the hospital?