Cardiac magnetic resonance imaging shows inflammation after recovery from Covid-19

Relation

Puntmann VO, Carerj ML, Wieters I, et al. Cardiovascular magnetic resonance imaging results in patients recently recovered from coronavirus disease 2019 (COVID-19).JAMA Cardiol. 2020:e203557. doi:10.1001/jamacardio.2020.3557 [Epub ahead of print].

Study objective

To determine whether myocardial injury and/or inflammation is present after recovery from recent Covid-19

Draft

Prospective observational study comparing cardiac magnetic resonance (CMR) of unselected participants recovered from Covid-19 with healthy controls and with risk factor-matched controls

Participant

The study included 100 patients, 53% male and mean age 49 years, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription-polymerase chain reaction on 2 upper respiratory tract swab tests and who subsequently recovered underwent CMR. Patients with cardiac symptoms referred for CMR were excluded, as were those who had absolute contraindications to contrast-enhanced CMR. Researchers compared CMR results from 100 recovered patients with 50 age- and sex-matched healthy controls who were normotensive and not taking cardiac medications. Researchers also compared the recovered group with 57 volunteers matched for age, gender and cardiovascular risk factors. The median time interval from diagnosis of Covid-19 to CMR was 71 days.

Study parameters assessed

• CMR
• Bluttests:
• Hochempfindliches C-reaktives Protein (hs-CRP)
• Hochempfindliches Troponin T (hs-TnT)
• N-terminales natriuretisches Peptid vom Pro-b-Typ (NT-proBNP)

Key insights

Of the 100 participants who recovered from Covid-19, 78% had evidence of cardiac involvement on CMR imaging, while 60% had evidence of myocardial inflammation - statistically more CMR abnormalities than any comparison group. The recovered participants also had statistically significant ejection fraction in the lower left ventricle and higher troponin T levels than both control groups. The extent of cardiac involvement did not correlate with Covid-19 disease severity or symptoms; 67% of participants had recovered at home.

Practice implications

This paper has caused concern in both medical and lay circles. Evidence that cardiac inflammation and reduced left ventricular ejection fraction may be present 10 weeks after resolution of Covid-19 is of concern, particularly as the severity of infection did not correlate with the extent of cardiac sequelae. Heart inflammation was seen even in some with mild illness: 67% of participants recovered at home. The editorial in the same issue ofJAMA Cardiologytitled “Coronavirus disease 2019 (COVID-19) and the heart – is heart failure the next chapter?”¹caused a lot of unrest. The same issue also published the results of 39 consecutive autopsies of Covid-19-related deaths, which showed virus particles in the heart.²The articles received a lot of press and were cited by colleges when they canceled football programs.

Basing any suggestion of inevitable heart failure on a non-randomized CMR study of 100 unselected participants is premature and potentially frightening.

Almost immediately after publication, Professors Darrel Francis and Graham Cole from the United Kingdom noted in a Twitter feed that the data points and results in Table 1 of the paper were mathematically impossible.³Puntman et al. reanalyzed, added missing data and wrote an answer,⁴andJAMA Cardiologycorrected the original online version (errors in statistical figures and data). In the reanalysis, left ventricle mass was not statistically higher in the recovered group, but all other measurements retained statistical significance.

Since Covid-19 was first reported less than a year ago, much has been established about its relationship to heart disease. The presence of pre-existing cardiovascular disease and its risk factors high blood pressure, diabetes, smoking and obesity are associated with higher rates of Covid-19-related hospitalizations and deaths.⁵Up to 40% of patients hospitalized with Covid-19 have pre-existing cardiovascular disease.⁶Myocardial injury, as measured by troponin, is common in patients hospitalized with Covid-19. In a series of 3,000 patients hospitalized at Mount Sinai Medical Center in New York City, 36% had evidence of myocardial injury.⁷This was associated with a higher death rate. In the above-mentioned series of 39 consecutive autopsies of patients who died of Covid-19-related causes, 61% showed evidence of viruses in heart cells.²In an 11-year-old girl who died from multisystem inflammatory syndrome related to Covid-19, the virus was observed in cardiomyocytes, endothelial cells, mesenchymal cells and inflammatory cells.⁸The authors hypothesized that the virus directly caused myocarditis in this child.

These studies raise the following questions:

• Greift Covid-19 das Herz direkt an und schädigt es dauerhaft?
• Wie lange dauert eine Herzentzündung nach Covid-19?
• Sollten Entzündungsmarker als Screening-Instrumente bei Personen mit einer Vorgeschichte von Covid-19 verwendet werden?
• Werden sich Kardiomyopathie und Herzinsuffizienz aus einer Covid-19-bedingten Herzentzündung entwickeln?
• Obwohl CMR die Visualisierung von Herzentzündungen ermöglicht, wie sollten Ärzte sie in der klinischen Praxis einsetzen?

Basing any suggestion of inevitable heart failure on a non-randomized CMR study of 100 unselected participants is premature and potentially frightening. Additional research with long-term follow-up in selected populations is needed. Studies in Covid-19 survivors are underway to help answer these questions and include cardiac follow-up of Covid-19 pneumonia (ClinicalTrials.gov NCT04501822), participants with cardiomyopathy (ClinicalTrials.gov NCT04468256), and survivors with acute coronary syndrome (ClinicalTrials.gov NCt04333407). other.

What do we know and what can be done safely now to care for our patients? There are currently no proven herbal or supplement treatments for Covid-19, but measures known to reduce heart inflammation and pose little to no risk may be indicated.

Correlation studies suggest consideration of vitamin D, omega-3 fatty acids and melatonin. In a retrospective study of 489 patients who had vitamin D levels measured within a year before Covid-19 testing, 71 tested positive for Covid-19.⁹The authors concluded that vitamin D deficiency (25-hydroxycholecalciferol less than 20 ng/ml or 1,25-dihydroxycholecalciferol less than 18 pg/ml) was associated with a 21.6% absolute risk of Covid-19, in contrast to a 12.2% risk in the vitamin D sufficient group.

The anti-inflammatory omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have proven cardiovascular benefits.^10,11In a Cochrane review of 10 randomized trials involving 1,015 patients with acute respiratory distress syndrome (ARDS), EPA and DHA supplementation improved O2 saturation, shortened the length of hospital stay, and reduced mortality at 28 days.¹²

Melatonin is another candidate in the fight against Covid-19. Melatonin is a known antioxidant and anti-inflammatory agent with a good safety profile that is being evaluated in a double-blind, randomized, placebo-controlled trial in outpatients infected with COVID-19 (ClinicalTrials.gov NCT04474483).

Finally, there are 2 drug classes worth mentioning: statins and ACE inhibitors. In a meta-analysis that included 8,990 Covid-19 patients, statin use correlated with an approximately 30% reduced incidence of severe disease.¹³This is not surprising given the anti-inflammatory effects of statins. In the early months of the pandemic, there was concern that angiotensin-converting enzyme (ACE) inhibitors could increase infection because they lead to upregulation of ACE-2 receptors, the docking ligand of SARS-CoV-2. Current reviews¹⁴and a randomized trial^fifteenindicate that these medications can be safely continued in patients with Covid-19.

Both the mentioned drugs and the nutritional supplements have immunomodulatory effects that reduce several pathways involved in cardiac inflammation. There is no data on initiation of statins and ACE inhibitors during a Covid-19 diagnosis, but evidence suggests that these medications should not be stopped during the illness. Vitamin D, omega-3 fatty acids and melatonin are generally well tolerated and have a good safety profile. Their initiation and continuation during Covid-19 is likely safe and potentially beneficial.

In my opinion, the strongest anti-inflammatory is avoiding the inflammatory stimulus, in this case SARS-CoV-2. Prevention through masking, physical distancing and a healthy lifestyle are the most reliable means to avoid the possible cardiac consequences of infection.