A 70 year old man presents to your Emergency Department (ED) with a three week history of cough and mild shortness of breath, but this is improving. Over the last two days he has had several discrete episodes of epigastric pain, not associated with food, that have self resolved.
On examination he is comfortable at rest, with no epigastric tenderness. Vital signs are normal. His ECG shows left bundle branch block and a “zero hour” high sensitivity cardiac troponin (hs-cTn) is 170ng/l. When this is repeated three hours later it is now 350ng/l.
You reach for the phone to contact the on call cardiologist, and start writing up medications for acute coronary syndrome when a new guideline entitled “Summary and guidelines for COVID-19 myocardial injury” is thrust your way…..
High Sensitivity Troponin (hs-cTn) in the ED
Anyone who has read St Emlyn’s for any period of time will know that we are big proponents of High Sensitivity Troponin, when used correctly. This is in no small part influenced by Rick Body being one of the world’s leading researchers in the field.
For anyone who feels they need a refresher on high sensitivity troponin you can read Rick’s posts here or listen to this series of podcasts.
High sensitivity cardiac troponin is released whenever there is myocardial injury. Usually in the ED we are using a negative result or results to try to rule out if a patient presenting with chest pain has acute coronary syndrome (ACS).
A “rise and/or fall in high sensitivity troponin” forms part of the “Universal Definition of Type 1 Myocardial Infarction(1)” when accompanied by signs of acute myocardial ischaemia. However, we also know that there are many reasons for an elevated troponin in patients admitted to hospital, with one series stating that 1 in 20 of all admissions(2) had a higher level than the accepted 99th percentile. Acute coronary syndrome is not the only reason for a raised hs-cTn, in fact the list of other possible causes is extensive(1).
Potential causes of a raised hs-cTn
The Heart, Troponin and COVID-19
There have been several mechanisms postulated for the acute myocardial injury, and subsequent rise in hs-cTn with concurrent COVID-19 infection.(3) that may not be due to an imbalance between oxygen demand and supply.
Angiotensin Converting Enzyme 2 receptors, is the proposed viral entry mechanism into cells. ACE2 is widely expressed not only in the lungs but also in the cardiovascular system and, therefore, ACE2-related signalling pathways might also have a role in direct cardiac injury. Other proposed mechanisms of myocardial injury include a cytokine storm triggered by an imbalanced type 1 and type 2 T helper cell response, respiratory dysfunction and hypoxaemia, resulting in damage to myocardial cells and stress cardiomyopathy (worsened also by adrenergic stimulation).
Although acute myocardial injury and heart failure are seen in a proportion of patients with COVID-19 the origin of this is not always clear. Some of these may indeed be due to myocarditis, but, as stated above, troponin elevation in critically ill patient groups is not uncommon and whether heart failure cases are due to exacerbation of pre-existing left ventricular dysfunction versus new cardiomyopathy (either due to myocarditis or stress cardiomyopathy) remains uncertain.
In one retrospective cohort study of 191 patients with COVID-19, 17% had raised hs-cTn, or new abnormalities on electrocardiography and/or echocardiography. New, or worsening heart failure was common, affecting 23% in the same study(4).
We also are now recognising that COVID-19 patients with significantly raised hs-cTn have more severe disease and it is associated with a poorer prognosis.(5)
Myocarditis – A Refresher
One of the causes of a raised troponin in patients with COVID-19 is myocarditis: an inflammatory cardiomyopathy. It presents in a wide variety of ways, from mild chest pain to life threatening cardiogenic shock and ventricular arrthymias. It can be found at post mortem in up to 42% cases of sudden cardiac death(6). We perhaps shouldn’t be surprised that COVID-19 can cause myocarditis, as the most common previously described causes are other RNA viruses such as Coxsackieviruses A and B.
The ECG in patients with myocarditis is usually abnormal, but the changes are neither sensitive nor specific. Generally the changes are diffuse and concave (rather than convex as seen in ischaemia) and without reciprocal changes(7).
Prior to COVID-19 an Echocardiogram was recommended for all patients with suspected myocarditis. It helps to rule out other non inflammatory cardiac disease and to monitor changes in cardiac chamber size, wall thickness, ventricular function, and pericardial effusions.(8)
Treatment is generally supportive and the prognosis good. For the unfortunate few who have fulminant cases mechanical cardio-pulmonary assist devices and ultimately transplantation may be the only options, with extracorporal membrane oxygenation (ECMO) used as a bridge until this is available.
Due to the pro arrthymogenic nature of the inflammation exercise should be restricted after the acute phase has settled and in some an implantable cardioverter defibrillator may be necessary.
The COVID-19 Cardiac Clinical Dilemma in the ED
It should probably come as no surprise to us that patients with COVID-19 may also have raised hsTrop, beyond the 99th centile, after all these patients are often profoundly hypoxic.
Many of us have seen a huge decrease in the number of patients attending the ED during the first few weeks of the Corona Shutdown, but there must, surely(!), still be patients having acute coronary syndrome (ACS), or even myocardial infarctions? In the same way that all raised troponins aren’t ACS, we must also remember that all shortness of breath isn’t just COVID-19.
So how do we tell the difference between a hs-cTn rise due to acute coronary syndrome and one secondary to COVID-19 and cardiac inflammation. The last thing we want to do is admit a patient who is having a heart attack, and may benefit from urgent coronary angiography, to a respiratory isolation ward.
The first thing we must always do (pandemic or not) is consider the clinical situation in which we have got our raised troponin. Does the patient have ischaemic sounding pain? Are there ECG changes consistent with a regional ischaemic insult? Are there other indications that this could be COVID-19 (chest X ray changes, profound type 1 respiratory failure, etc) or another condition.
The ECG may or may not be helpful – as stated above the changes are often non specific, but for many of us this (plus a raised hs-cTn) would have been more than enough to warrant a CCU admission in the not so recent past.
A bedside echo could be useful, but we have to remember that we do not want to expose healthcare staff to coronavirus unnecessarily (and in proven or suspected cases of COVID-19 the use of valuable PPE would also be mandated). Any investigations that we perform have to make a difference to the patient’s treatment course.
A suggested ED approach to raised hsTrop during the COVID-19 pandemic.
The following is adapted from local guidance produced at University Hopsital Southampton.
1, Could this be ischaemia? Is there a convincing clinical picture? Are any of the following present along with a rise and/or fall of hs-cTn values with at least one value above the 99th percentile and with at least one of the following:
- Symptoms of acute myocardial ischaemia;
- New ischaemic ECG changes; especially if they are related to a particular coronary artery and accompanied by reciprocal change.
- Development of pathological Q waves;
2, Likely COVID-19 patients with myocardial injury as evidenced by an elevated troponin and any of the following could be considered for focused echocardiography for assessment of left ventricular systolic function if it is felt likely to inform patient management:
- Haemodynamic instability (hypotension & tachycardia not responsive to fluid challenge)
- Clinical symptoms or signs of myocarditis/heart failure – chest pain, elevated JVP, development of pulmonary congestion / effusions or significant peripheral oedema
- Arrhythmia – clinical judgement should be exercised in the context of new atrial fibrillation. ECG changes – New ST depression / elevation or T-wave inversion
3, In cases of COVID related myocardial damage the degree of troponin elevation correlates with the severity of myocardial injury. In cases with significantly elevated troponin (>1000ng/l) a lower index of suspicion for clinically important cardiac dysfunction secondary to COVID-19 infection should be adopted. (We use the Beckman Coulter Access AccuTnI+3 assay at UHS).
4, Management of cardiac involvement in COVID-19 infection is generally supportive and it is anticipated that most cases will be self-limiting.
5, In rare cases, myocarditis can progress to severe LV dysfunction causing refractory cardiogenic shock. In the absence of any contraindication, consideration may be given to mechanical circulatory support (ECMO).
6, Patients with myocarditis should be advised to avoid exercise, NSAIDS and alcohol for 3 months.
Not everything is COVID-19, but as our knowledge grows we are beginning to understand that this virus seems to affect more than just the respiratory system.
A raised troponin in the context of symptoms suggestive of COVID-19 may be due to myocarditis, many cases of which are mild, do not need specialist cardiology input and will resolve with supportive treatment.
Fulminant myocarditis is a potential cause of mortality in patients with COVID-19
Be sure to always consider other diagnoses, before assuming anything is purely down to coronavirus. Some of these patients may well be having myocardial infarctions and this should be actively ruled out.
1, Curzon et al. True 99th centile of high sensitivity cardiac troponin for hospital patients: prospective, observational cohort study. BMJ 2019;364:l729
2, Kristian Thygesen et al, Fourth universal definition of myocardial infarction (2018) European Heart Journal, Volume 40, Issue 3, 14 January 2019, 237–269
3, Chapman et al, High-Sensitivity Cardiac Troponin Can Be An Ally in the Fight Against COVID-19. Circulation 2020; 6th April epub ahead of print
4, Zhou F, Yu T. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020. Published online March 9.
5, Guo T et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disesase 2019 (COVID-19). JAMA Cardiol 2020 Mar 27: (e-pub)
6, Basso C et al. Postmortem diagnosis of sudden cardiac death victims. Cardiovasc Res 2001; 50: 290-300
7, Myocarditis ECG changes. Life in the Fast Lane. https://litfl.com/myocarditis-ecg-library/ (accessed 12th April 2020)
8, Caforio A et al. Current state of knowledge on the aetiology, diagnosis, managament and therapy of myocarditis:a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. European Heart Journal (2013) 34, 2636-2648
After publication Dr Stephen Smith, ECG guru and all round nice chap got in touch with this message:
A couple things:
1) Wall motion abnormality is present in both MI and myocarditis.
2) Focal ECG findings (including reciprocal ST depression) is present in myocarditis
3) Probably best ECG predictors are: MI has larger T-waves (higher T/ST ratio) and myocarditis more PR depression. Differentiation in COVID seems to be difficult but there is very little data. Gold standard is of course MRI or biopsy, both difficult to obtain in COVID patients. –Steve