Following a Twitter takedown, they addressed study errors but still cite lingering cardiac damage. One expert disagrees.
Investigators who led a widely publicized cardiac magnetic resonance (CMR) study showing that COVID-19 may cause lingering cardiac damage have responded to questions raised on social media challenging their findings.
Eike Nagel, MD, and Valentina Puntmann, MD, PhD (both University Hospital Frankfurt, Germany), issued a correction this week in JAMA Cardiology, stating they reviewed and reanalyzed their data after TCTMD alerted to them Twitter discussions about their work. While they identified a few other errors as part of their reanalysis, once all the mistakes were accounted for and corrected, they say, the initial message of their CMR study still stands.
“We are pleased to confirm that reanalysis of the data has not led to a change in the main conclusions of the study,” write Nagel and Puntmann in a letter to the editor. On the group’s website, the researchers go on to say they “are reassured that the validity of the originally published results remains solid and the message unchanged.”
That message, as reported by TCTMD, is that COVID-19 may result in lasting cardiac damage even in nonhospitalized patients. In a study of 100 people who recovered from COVID-19, 78% had abnormal CMR findings 2 to 3 months after initially testing positive for the virus. Compared with healthy and risk factor-matched controls, patients who recovered from COVID-19 had lower LV ejection fractions, higher LV volumes, and elevated values of native T1 and T2 on CMR.
Recovered COVID-19 patients, in that first paper, also had a high LV mass index compared with healthy controls, but that association was no longer statistically significant after the researchers obtained missing data from the original CMR scans, the correction notes.
JAMA Cardiology editor Robert Bonow, MD, and deputy editor Clyde Yancy, MD (both Northwestern University Feinberg School of Medicine, Chicago, IL), also weighed in, issuing a brief letter accompanying the correction. They proceeded with a repeated statistical review—and requested reanalysis and revision by the original investigators—following questions raised after the study’s publication, they write. “A rigorous review has confirmed that the findings as originally reported remain valid.”
After the study was published on July 27, 2020, Darrel Francis, MD, and Graham Cole, MBBS, PhD (both Imperial College Healthcare NHS Trust, London, England), challenged some of its numbers, questioning whether key values were reported as medians instead of means. In another instance, Cole identified a patient with a high-sensitivity cardiac troponin T (hs-cTnT) of 17.8 pg/mL in Figure 1 but was unable to find that patient in Figure 3 that plotted hs-cTnT levels against the time since diagnosis.
In their letter to the editor, Nagel and Puntmann said some of the metrics for key values were not reported correctly and that they have since updated the paper to include the accurate means (standard deviations) or medians (interquartile ranges). They also acknowledge inconsistencies in key figures, stating that data for the time between COVID-19 diagnosis and the CMR images and hs-cTnT were not reported correctly—this, they say, led to problems with Figure 3. During their review, the researchers discovered other mistakes that they have now corrected.
“While reviewing the complete data set for any other potential errors, we also benefited from some additional data which had become available, as well as the journal’s statistical advice, and took the opportunity to improve the presentation of certain results,” write Nagel and Puntmann on their website. While some P values may have changed, the main message is consistent.
Speaking with TCTMD about the revisions, as well as the statement that the conclusions are unchanged, Francis had a completely different take, saying that, in his view, this study and specifically these new data do not raise any alarms about the lingering cardiac effects of COVID-19. He praised the researchers for their responsiveness in updating their tables and figures to reflect the most accurate data, but asserted that their reading of the study should be updated as well.
“I look at their interpretation being only correct for the out-of-date data, and I hope they agree that the new data is now fully reassuring,” he said. “I appreciate them for making it available so quickly.”
As he was on Twitter, Francis continues to remain critical of the group’s statistical analysis. While the researchers included P values showing significant differences in the blood test results and CMR findings between the three study groups, the P value for a three-arm comparison is unhelpful because it includes a healthy control group who’d be expected to have much better lab and CMR results than COVID-19 patients, he said. Instead, the most important comparator arm is the risk factor-matched control group, and when looking at those cohorts, the difference in abnormal CMR findings isn’t nearly so striking, Francis argued.
“The COVID-19 survivors have different heart scans than the healthy controls, but this is because of their preexisting risk factors and not because of COVID-19,” he said. In a two-arm comparison of the abnormal native T1 findings on CMR, Francis said there isn’t any significant difference between the COVID-19 patients and risk factor-matched controls.
Francis also focused on the blood test results, which included some values that were adjusted as part of the corrected publication. Unlike interpreting CMR images for evidence of cardiac damage, interpreting the laboratory values is rather “straightforward,” he said. When looking only at high-sensitivity C-reactive protein, hs-cTnT, and NT-proBNP values, Francis said there isn’t much evidence that patients with COVID-19 look any worse in follow-up than patients with similar cardiovascular risk factors.