Heart Damage Even After COVID-19 'Recovery' Evokes Specter of Later Heart Failure

July 29, 2020

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Evidence that the heart can take a major hit in patients hospitalized with COVID-19, especially those already with cardiovascular disease (CV) or its risk factors, has been sadly apparent from the pandemic's earliest days.

Less clear from case studies and small series to date has been whether SARS-CoV-2 directly attacks the heart, and whether acute cardiac effects of the illness may lead to some kind of lingering cardiomyopathy.

The field's grasp of those issues advanced a bit in two new reports published July 27 in JAMA Cardiology that seem to validate concerns the virus can infect the myocardium, without necessarily causing myocarditis, and the possibility that some "recovered" patients may be left with persisting myocardial injury and inflammation that potentially could later manifest as heart failure.

Persisting Inflammation by CMR

A prospective cohort study with 100 patients recovered from a recent bout of the disease showed evidence of ventricular dysfunction, greater ventricular mass and, in 78% of the cohort, signs of myocardial inflammation by cardiac magnetic resonance (CMR) imaging. The CMR findings correlated with elevations in troponin T by high-sensitivity assay (hs-TnT).

Two-thirds of the cohort, whose acute COVID-19 severity had "ranged from asymptomatic to minor-to-moderate symptoms," had recovered at home, whereas the remaining "severely unwell patients" had been hospitalized, write the authors, led by Valentina O. Püntmann, MD, PhD, University Hospital Frankfurt, Germany.

None of the patients had a history of heart failure or cardiomyopathy, although some had hypertension, diabetes, or evidence of coronary disease.

"Our findings demonstrate that participants with a relative paucity of preexisting cardiovascular condition and with mostly home-based recovery had frequent cardiac inflammatory involvement, which was similar to the hospitalized subgroup with regards to severity and extent," the group notes.

"There is a considerable ongoing myocardial inflammation in the heart muscle weeks after recovery from COVID-19 illness. This finding is important because it may herald a considerable burden of heart failure in a few years down the line," Püntmann told theheart.org | Medscape Cardiology.

Early diagnosis would offer "a good chance that early treatment could reduce the relentless course of inflammatory damage or even halt it," she said.

"The relatively clear onset of COVID-19 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, within a few weeks of recovery."

The study's CMR evidence of inflammation edema, scarring, and pericardial effusion are among "the major diagnostic criteria for inflammatory and viral myocarditis," observed Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, who wasn't part of either new study.

The findings suggest — consistent with previous evidence — that some patients with recent COVID-19 may be left with ongoing myocardial inflammation, and this study further adds that it could potentially become subacute or even chronic, and in some may not be totally reversible, she told theheart.org | Medscape Cardiology. How long the effects are likely to persist "remains to be determined. We need longer-term outcomes data."

Viral Presence Without Myocarditis

The accompanying report featured a postmortem analysis of hearts from 39 patients with mostly severe COVID-19 that pointed to a significant SARS-CoV-2 presence and signs that the virus vigorously replicated in the myocardium.

But there was no evidence that the infection led to fulminant myocarditis. Rather, the virus had apparently infiltrated the heart by localizing in interstitial cells or in macrophages that took up in the myocardium without actually entering myocytes, conclude the report's authors, led by Diana Lindner, PhD, University Heart and Vascular Centre, Hamburg, Germany.

The findings suggest "that the presence of SARS-CoV-2 in cardiac tissue does not necessarily cause an inflammatory reaction consistent with clinical myocarditis," the group writes.

Previously in the literature, in "cases in which myocardial inflammation was present, there was also evidence of clinical myocarditis, and therefore the current cases underlie a different pathophysiology," they conclude.

No evidence of the virus was seen in 15 cases, about 61% of the group. In 16 of the remaining 24 hearts, the viral load exceeded 1000 copies per μg of RNA, a substantial presence. Those 16 showed increased expression of inflammatory cytokines but no inflammatory cell infiltrates or changes in leukocyte counts, the researchers note.

"Findings of suggested viral replication in the cases with a very high viral load are showing that we need to do more studies to find out long-term consequences, which we do not know right now," senior author Dirk Westermann, MD, also from the University Heart and Vascular Centre, Hamburg, said for theheart.org | Medscape Cardiology.

Implications for Heart Failure

The postmortem findings from Lindner and associates "provide intriguing evidence that COVID-19 is associated with at least some component of myocardial injury, perhaps as the result of direct viral infection of the heart," write Clyde W. Yancy, MD, MSc, Northwestern University, Chicago, and Gregg C. Fonarow, MD, University of California, Los Angeles, in an editorial accompanying both reports.

The CMR study from Puntmann and colleagues — on the backdrop of earlier COVID-19 observations — suggests the potential for "residual left ventricular dysfunction and ongoing inflammation" in the months following a COVID-19 diagnosis. Both developments may be "of sufficient concern to represent a nidus for new-onset heart failure and other cardiovascular complications," contend Yancy and Fonarow.

"When added to the postmortem pathological findings from Lindner et al, we see the plot thickening and we are inclined to raise a new and very evident concern that cardiomyopathy and heart failure related to COVID-19 may potentially evolve as the natural history of this infection becomes clearer," they write.

Some patients, having recovered from the acute illness, may be left with a chronic inflammatory state that probably puts them at increased risk for future heart failure, agreed Bozkurt when interviewed. "They could show further decline in cardiac function, and their recovery might take longer than with the usual viral illnesses that we see," she said.

"There could also be a risk of sudden death. Inflammation sometimes gives rise to sudden death and ventricular arrhythmia, which I would be very worried about, especially if the myocardium is stressed," Bozkurt said. "So competitive sports in those patients potentially could be risky."

COVID-19 Cohort vs Matched Control Subjects

The CMR study from Püntmann and colleagues prospectively entered 100 patients recently recovered from an acute bout of COVID-19, either at home or at a hospital, who were followed in a registry based at University Hospital Frankfurt. Their median age was 49 years; 47% were female.

They were compared with 50 age- and sex-matched control patients and 50 apparently healthy volunteers matched for risk factors, the group notes.

On the same day as the CMR assessment, the recently recovered patients, compared with the healthy control subjects and risk-factor matched control subjects, respectively (P ≤ .001 in each case), showed a:

  • reduced left ventricular (LV) ejection fraction: 56% vs 60% and 61%

  • higher LV end-diastolic volume index: 86 mL/m2 vs 80 mL/m2 and 75 mL/m2

  • greater LV mass index: 51 g/m2 vs 47 g/m2 and 53 g/m2

  • higher hs-TnT level: 5.6 pg/mL vs 3.2 pg/mL and 3.9 pg/mL

  • greater prevalence of hs-TnT levels 3 pg/mL or more: 71% vs 11% and 31%

At CMR, 78% of the recovered COVID-19 patients showed abnormalities that included raised myocardial native T1 and T2 mapping, suggestive of fibrosis and edema from inflammation, compared with the two control groups (P < .001 for all differences), "independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis," the group writes. Native T1 and T2 mapping correlated significantly with hs-TnT.

"We now have the diagnostic means to detect cardiac inflammation early, and we need make every effort to apply them in every day practice," Püntmann told theheart.org | Medscape Cardiology.

"Using cardiac MRI will allow us to raise our game against COVID-19 and proactively develop efficient cardioprotective treatments," she said. "Until we have effective means of protecting from the infection, that is vaccination, we must act swiftly and within the means at hand."

The analysis evokes several other ways patients with COVID-19 might be screened for significant myocardial involvement.

"Strategies could include checking troponins, not only at admission but maybe at discharge and perhaps even those individuals who are at home and are not necessarily requiring care," Bozkurt said.

"Biomarker profiling and screening for ongoing inflammation probably are going to be important components of COVID-19, especially for those with subclinical risk and disease."

Westermann proposed that troponin elevations at discharge "might be a good starting point" for selecting COVID-19 patients for functional testing or imaging to screen for cardiac sequelae. Performing such tests routinely now "would be overwhelming given the massive increase in patients we still see today."

Püntmann had no disclosures; statements of potential conflict for the other authors are in the report. Bozkurt has previously disclosed receiving consultant fees or honoraria from Bayer Healthcare, Bristol-Myers Squibb, Lantheus Medical Imaging, and Respicardia; serving on a data safety monitoring board for LivaNova  USA ; and having unspecified relationships with Abbott Laboratories. Lindner had no disclosures; Westermann reports receiving personal fees from AstraZeneca, Bayer, Novartis, and Medtronic. Yancy is a deputy editor and Fonarow a section editor for JAMA Cardiology. Yancy had no other disclosures. Fonarow reports receiving personal fees from Abbott Laboratories, Amgen, AstraZeneca, Bayer, CHF Solutions, Edwards Lifesciences, Janssen, Medtronic, Merck, and Novartis.

JAMA Cardiol. Published online July 27, 2020. Full text, Püntmann et al. Full text, Lindner et al. Editorial

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