Frequently Asked Questions
Link to the Paper
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Main Messages
- There is a considerable ongoing myocardial inflammation in the heart muscle weeks after 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 CMR approaches (like the Goethe-CVI® Approaches), not any routine CMR can deliver that. Also, scans must be humane (i.e. short, ours last 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.
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. 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 is quite 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).
Did you expect such a high cardiac involvement?Once the first reports of severe autoimmune disease, the 'cytokine storm' and similar, were mentioned, we immediately understood that the heart would have also been involved, because myocarditis is essentially an autoimmune problem. The high prevalence and extent, however, surprised us.
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 lab 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 go about this. One way could be a troponin blood test. However, troponin is a test to diagnose acute complications of coronary artery disease such as the 'heart attack’. It has never been validated for the use in myocarditis, meaning, that the cut-off values for heart attack cannot be used for 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 one know 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.
How generalizable are your findings (how characteristic was your population)?Our patients were the ‘common people’ who got themselves tested (we identified them through our testing center, not through hospital admission). These were not patients with known heart disease or presenting due to ongoing cardiac symptoms.
Did the patients have any risk factors for cardiac involvement of the virus?An overall 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.
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Do patients have cardiac symptoms?The absence of typical heart-specific symptoms in myocarditis is very important. We cardiologists assume the symptoms of a heart attack as the 'one-type fits-all textbook cardiac symptoms' and expect that every heart condition will present like that. On the contrary, myocardial inflammation has a completely different pathophysiological pathway (evolution of disease) than heart attack. First, there is to an injury to the heart muscle (likely during the acute COVID illness and it is still unclear if necessarily by the virus itself). This triggers slow evolution of diffuse muscular inflammation, which takes a few weeks - months. This is in most cases silent or subclinical (ie. under the threshold of our current classification of cardiac symptoms) for many years. Eventually, structural changes of the heart happen, giving away non-specific symptoms, such as reduced fitness or shortness of breath on exertion. Finally, the heart has accumulated a lot of damage and large amounts of fibrosis. This is when patients develop heart failure. In our view, the relatively 'clear onset of COVID19 illness’ provides an opportunity - which we often do not have with other conditions - to take a proactive action and to look for heart involvement early, i.e. within a few weeks from recovery.
Is there an active virus replication in myocardium?In our biopsies we found no evidence of viral particles. I.e. infection is the initial trigger the antigen-presentation, which is most commonly myoglobin. Cardiac inflammation is likely perpetuated through an autoimmune process. In some people, this is self-limiting, in others, this may lead to permanent inflammation -> inflammatory cardiomyopathy -> heart failure. Virus particles have been demonstrated in acute cases and postmortem examinations, i.e. very severe cases.
Can you recommend post-recovery therapies?Currently we have no evidence that CMR could guide us in terms of treatment. The standard heart failure therapy cannot be recommended as most patients will have normal - preserved ejection fraction. In short, 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 are currently not very good at taking proactive therapeutic action prior to the development of heart failure (also known as cardio-protection), simply because they do not know how to look for signs early enough. Many would also not know that cardiac MRI can help with that. The reason for this is that not many will have an easy access to cardiac MRI, and even less, would have the training to make a good use of its findings. 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.
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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.
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 for any other potential errors, we have also benefited from some additional data which had become available. We were also provided by 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.
