Frequently Asked Questions
Link to the Paper
Main Messages
- There is a considerable ongoing myocardial inflammation in the heart muscle weeks-months after the recovery from the acute COVID19 illness. This finding is important because it may herald a considerable burden of heart failure in a few years from now.
- Early diagnosis is important because there is a good chance that early treatment could reduce the relentless course of inflammatory damage or even halt it. To prove this, we need clinical trials most urgently.
- It matters to use cardiac MRI as the diagnostic test of choice, because it is very sensitive to detect myocardial inflammation. However, we need to use standardised and validated cardiac MRI tools (like the Goethe-CVI® Approaches), not any routine CMR can deliver that. Also, scans must be humane (i.e. short, our scans are designed to deliver the maximal clinical information in the shortest amount of scanning time, lasting only about 20 min).
- We need to make the efforts to make MRI machines available for cardiac indications, because it prognostically matters most what happens with the heart.
- We need to give the heart time to heal, even if there is a paucity of symptoms. We recommend avoiding strenuous sports for at least 6 months after the acute illness, even if patients have no symptoms at all. We also guide our patients with imaging evidence of an ongoing inflammation.
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Cardiac magnetic resonance is the diagnostic test of choice for inflammatory cardiomyopathies, as it is very sensitive to detect inflammation directly within the tissue of the heart. In the video below, Dr Puntmann explains the typical findings in the heart in a young patient with Long COVID symptoms.
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Why are the findings important?Our findings are important because they may herald a considerable burden of heart failure in a few years from now. Cardiac involvement may not be the most visible part of the acute illness, however, it is detectable in a considerable proportion of patients a few weeks later. While we do not yet have any direct evidence for any late consequences yet, such as development of the heart failure, which can be directly attributed to COVID19, it may be possible that in a few years, this burden will be considerable, based on what we know from other viral conditions that similarly affect the heart (cardiotropic vira, swine flu, etc).
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Cardiac Symptoms and Long COVIDPatients with long COVID often develop symptoms that relate to cardiac involvement, including resting tachycardia or even POTS; or shortness of breath, especially when attempting the inclines. These two reflect stiffer heart muscle due to myocardial inflammation. Some patients also have mildly reduced pumping function. Patients also report burning chest pains or deep chest discomfort, often migrating towards the back or getting worse on inspiration. These symptoms relate to the inflammation of the heart's lining, the pericarditis.
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Do patients with myocarditis have cardiac symptoms?Cardiologists often assume that myocarditis is a very severe disease and expect it to present either with symptoms of heart failure or cardiogenic shock. In fact most patients have much milder versions of myocardial inflammation and not much in a way of typical heart-specific symptoms in myocarditis. It is also believed that most patients will heal swiftly and with no residual damage to the heart. Yet, our serial observations in viral myocarditis patients reveal that the healing process takes several months to a year to really complete. In a considerable proportion of patients there is a silent or subclinical (ie. under the threshold of our current classification of cardiac symptoms) ongoing myocardial inflammation and build-up of diffuse fibrosis, whereas the areas of necrosis noted in the acute stages, often heal with a residual scar. In some patients, these structural changes of the heart eventually give away some symptoms, such as reduced fitness or shortness of breath on exertion. Finally, the heart may become so damaged, which is when patients develop heart failure.
Do we need early diagnosis?Early diagnosis is important because there is a good chance that early treatment could reduce the relentless course of inflammatory damage or even halt it. However, myocarditis - as also shown in our patients - is prevalently a silent pathology (i.e. subclinical). In myocarditis heart problem does not present with classical heart chest pain, such as angina. Early diagnosis helps to clarify why patients are not fully recovering, possibly reduce high-level activity for some time and to guide therapy (see below).
Should we use regular imaging or blood tests?Given the subclinical course and evolution, the severity of this condition cannot be judged based on the symptoms. Thus, establishing an accurate way to objectivising the heart involvement would be invaluable, so we can proactively look for the evidence of cardiac inflammation in patients with recovering from the acute COVID19 illness. However, it matters profoundly how to go about this. One way to detect cardiac damage is a troponin blood test. However, troponin is a test to diagnose acute complications of coronary artery disease such as the 'heart attack’. The established cut-off values have been trained on the population of patients with suspected heart attack. It has never been validated for the use in myocarditis, meaning, the current cut-off values cannot be used to detect or exclude myocarditis. If we use the same cut-off values, we would likely send home a lot of patients that actually have a serious heart inflammation. Similarly, echocardiography, although widely available, is not a sensitive test for myocardial inflammation, because it simply cannot see inside the heart muscle tissue. In myocarditis, more often than not, pumping function remains normal in early stages (as also shown in our patients). If impaired, how would can you tell that this is not due to an old damage? We perform echo in parallel to cardiac MRI in all of our patients, so we know that there is a huge diagnostic gap between echo and MRI. Finally, in some countries, doctors would only rely on the biopsies of the heart muscle to confirm the heart inflammation, which is an invasive test, performed in a catheter lab. It is expensive, not widely available, not standardised (no clear cut-offs that relate to prognosis) and, most importantly, not without complications. The evidence that biopsies help to improve treatment is also missing. Clearly, myocardial biopsy cannot be rolled out as a scalable test for everyone.
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Did you expect such a high cardiac involvement?Once the first reports of severe autoimmune disease, the 'cytokine storm' and similar, were mentioned, we understood that the heart would have also been involved, because myocarditis is essentially an autoimmune problem. The high prevalence and extent, however, surprised us. However, our methods are very sensitive and especially suited for diffuse inflammation and fibrosis. We do not use Lake Louise Criteria due to the many limitations. This explains the higher capture in our study compared to others published more recently.
How generalizable are your findings?Our patients were the ‘common people’ who got themselves tested due to typical COVID symptoms (we identified them through our testing center, not through hospital admission). These were not patients with known heart disease or presenting due to cardiac symptoms, such as heart failure.
Did the patients have any preexisting conditions or cardiac involvement?Overall only a paucity of risk factors, a few had asthma and hypertension. They were generally fit and well and sporty – many of them caught the infection while on skiing vacation.
Can you recommend any postCOVID therapies? Currently we have not a lot of evidence for treatment of long COVID symptoms. The standard heart failure therapy can be initiated in those with reduced ejection fraction. For those with pericarditis, low dose colchicine treatment for 4 months can help. In those with severe resting tachycardia, beta-blockers and ivabradine can offer some relief. We urgently need clinical studies to inform us about any potential therapies that could offer cardio protection and prevent development of the heart failure.
It is important to note that doctors may not be very experienced at taking proactive therapeutic action prior to the development of heart failure symptoms (also known as the cardio-protection). Many would also not know that cardiac MRI can help with that. Not many will have an easy access to cardiac MRI, and even less, will have the training to make a good use of CMR findings. We are working hard to change this, so that the patients can finally benefit from the deeper insights offered by CMR. What drugs could be tested in clinical trials?In clinical trials, we could test a number of existing medications as well as test a number of potential candidates. However, for all this to be implemented in practice, we need further studies most urgently and we are inviting any interested parties to join us in our efforts to get this done. In a few years’ time, we might be overwhelmed not only by seriousness of the acute illness, but also with its chronic complications, ie. heart failure.
Is there an active virus replication in myocardium?In our biopsies we found no evidence of viral particles. This means that the infection likely acts as the initial trigger of myocardial injury which leads to the antigen-presentation, which is most commonly the myoglobin. Cardiac inflammation post COVID is most likely perpetuated through an autoimmune process. In some people, this is self-limiting, in others, this may potentially lead to permanent inflammation -> inflammatory cardiomyopathy -> heart failure. Virus particles have been demonstrated only in a paucity of patients that died during the acute disease.
How about the athletes ?This is indeed an area of a great uncertainty. We cannot really comment on it from the perspective of our study, because we did not look into athletes specifically. However, we would like to refer you to a recent paper in JAMA Cardiology, which provides some cautious guidance till we all learn more.
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Correction of the original article
The correction of the original article is a result of two inconsistencies highlighted by our colleagues Prof Darrel Francis and Dr Graham Cole, for which we have thanked them sincerely. While reviewing the complete dataset, we benefited from some additional data which had become available. We were also provided with the journal' statistical advice. As such, we took the opportunity to improve the presentation of certain results, for example a change from two-group comparisons vs the main COVID group to the three group comparisons. Consequently, many p-values have changed as a result of the test used, but not due to the change of its content. Further details are provided in our Letter to the editor.
We are reassured that the validity of the originally published results remains solid and the message unchanged. We most sincerely apologize for any confusion and appreciate the opportunity to correct the original publication. We thank the editors for support throughout this process and the readership for their understanding.
We are reassured that the validity of the originally published results remains solid and the message unchanged. We most sincerely apologize for any confusion and appreciate the opportunity to correct the original publication. We thank the editors for support throughout this process and the readership for their understanding.
