Tracking COVID-19 Acute, Persisting Effects on the Right Ventricle

May 27, 2020

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It may follow that the respiratory distress and myocarditis common in patients hospitalized with COVID-19 have an impact on the right ventricle (RV), but the acute effects and whether they create longer-lasting damage is less well understood.

A pair of recent reports in JACC: Cardiovascular Imaging looked at the utility of two different imaging windows on the heart for revealing RV dilation in such patients, which may help predict outcomes, and for showing ongoing postdischarge myocardial damage and RV dysfunction.

One of the reports describes a "focused, time-efficient" protocol for performing bedside echocardiography that aims to minimize sonographer and cardiologist contact with the patient and exposure to the SARS-CoV-2 virus. That could potentially make it safer to obtain echocardiograms more liberally in COVID-19 patients, researchers say.

In the retrospective study, 31% of more than 100 such patients with a clinical indication for echocardiography were found to have RV dilation, a feature that didn't track with myocardial inflammation or injury or with pulmonary embolism (PE). But it did independently predict more than a fourfold increase in in-hospital mortality.

The RV dilation wasn't continuous, typically. "From clinical experience and from reviewing all these echocardiograms myself, I can tell you that these changes are dynamic. We saw patients moving in either direction, going from normal ventricle to enlarged and going from enlarged to normalized," Edgar Argulian, MD, MPH, Icahn School of Medicine at Mount Sinai, New York City, told | Medscape Cardiology.

"All of the people who had RV enlargement underwent CT angiography to look for pulmonary embolisms, and only 50% of them had PE," which suggests the causes of RV dilation are more complex than often believed, said Argulian, who is lead author of the echocardiography study, which was published May 15.

The other report included findings on postdischarge MRI in 26 consecutive patients from one center in Wuhan, China, who had recovered from COVID-19 but later experienced cardiac symptoms, such as chest pain or palpitations; none had a pre-COVID-19 history of myocarditis or other heart disease.

Fifteen of the cohort, or 58%, showed MRI signatures for diffuse myocardial edema and for fibrosis by late-gadolinium enhancement (LGE), or for both along with impaired RV cardiac index and ejection fraction, despite preserved LV function. That was compared with 20 recent historical control subjects without documented cardiovascular or inflammatory disease who underwent the same MRI examinations.

"The presence of myocardial tissue abnormalities in otherwise healthy subjects suggests cardiac involvement as a lasting consequence of SARS-CoV-2 infection," findings that may be easily overlooked in patients with a mild form of the disease, write the authors, led by Lu Huang, MD, PhD, Tongji Medical College and Huazhong University of Science and Technology, Wuhan, in their report published May 11.

"The cardiac status of COVID-19 patients and survivors needs to be closely monitored; cardiac MRI can be a sensitive imaging tool in combination with laboratory tests for identifying cardiac involvement in COVID-19 patients," especially those with symptoms after apparent recovery, recommends the group of mostly radiologists.

However, the study looked at postdischarge myocardial changes on MRI without following up later, and "I would suspect that at 3 to 6 months, assuming the patient survives, you're not going to see much of them at all," proposed James A. Goldstein, MD, Beaumont Health System, Royal Oak, Michigan, for | Medscape Cardiology.

Moreover, it's unlikely the observed lesions would progress to severe RV failure, said Goldstein, who isn't associated with the report but has long studied RV function in different forms of heart disease. He cautioned that the study's few patients are "highly selected" and cautioned against drawing firm conclusions based on study.

The authors of the MRI report did not respond to requests for an interview.

Significant lung disease creates resistance that stresses the RV, "so it wouldn't be surprising if the RV enlarges and its pumping function goes down, which should be temporary as long as the lung recovers and as long as there has not been massive pulmonary emboli," Goldstein said.

"But the number of patients who suffer a big hit to the RV that really contributes, in a major way, to their outcome, I would think, is probably very small."

Still, he said, "doing an echo in someone with COVID makes sense. If there's any elevation in troponin, if there's any hemodynamic instability, and if the RV is a little large and a little bit sluggish, you note it — but all you're going to do is treat the lung disease."

The study from Argulian and colleagues involved 105 consecutive patients hospitalized with COVID-19 at a major center in March and April, who had evaluable echocardiograms obtained at bedside according to the streamlined, accelerated protocol designed to lessen clinician exposure to the virus. Echocardiograms from five other patients were excluded because they were of inadequate quality.

"We definitely didn't do all COVID patients who were hospitalized, we did only the ones where the team thought echocardiography would be clinically indicated and could change management," Argulian said in an interview.

"That would mean patients with quite significant symptoms: shortness of breath, chest pain, deterioration in hemodynamic status, and so on," he said. About 30% of the patients underwent echocardiography while on mechanical ventilation.

Imaging was performed by sonographers fully garbed in personal protective equipment who are trained in emergency echocardiography, "so they're very good at getting high-quality studies within a short time frame," Argulian said. Electrocardiography isn't part of the examination, to avoid lead placement and minimize contact with patient. Personnel leave the room before measurements are taken from the images.

The 32 patients with RV dilation didn't differ significantly from the remaining patients in major comorbidities, inflammatory biomarkers, troponins, or left ventricular size and function, but were significantly more likely to have renal dysfunction, the group reported.

They were also significantly more likely to have RV hypokinesis (66% vs 5%; P = .01) and moderate to severe tricuspid regurgitation (21% vs 7%; P = .05) than the patients without RV dilation. Five of the 10 patients who underwent thoracic CT angiography showed signs of PE.

Twenty-one and 13 patients, respectively (41% and 11%), died during hospitalization. In multivariate analysis, RV dilation was alone in independently predicting mortality (odds ratio, 4.5; 95% CI, 1.5 - 13.7; = .005).

Argulian noted that use of anticoagulation therapy tracked with a fast-growing appreciation of thrombotic risk associated with COVID-19 while these patients were accrued. The threshold for using it "became lower and lower. That was also partially driven by our findings, because as we saw a lot of our patients having RV enlargement, we speculated that thromboembolic events could be part of the cycle. So there was more liberal use of anticoagulation in these patients as we approached the study end."

It's possible, then, that growing use of anticoagulation will lead to less RV dilation, he said. "That's pure speculation, but you might think so."

But in the current series, he said, average anticoagulation use was similar in those with and without RV enlargement. "That was a bit surprising to me, because most of the RV enlargement events were thought due to thromboembolism."

So it's possible, he said, that RV dilation has multiple causes, including thromboembolic events but perhaps also hypoxemic pulmonary vasoconstriction, cytokine storm, coagulopathy, or direct effects from the virus.

"So I think this phenomenon is more complex than just simple PE," Argulian said. "I think it's a combination of things. The driving mechanism just needs to be further defined."

In any large series, Goldstein said, the number of patients on ventilation for COVID-19 who have "terrible RV function won't be zero, but it will be small." And it's patients with "terrible lung disease and big clots in the lungs" who will fare the worst.

"I suspect that in the vast majority with right ventricular dysfunction and dilatation, dysfunction is going to be temporary and recover, unless the patient ends up with end-stage lung disease," Goldstein said.

Taken together, the two current reports "show that the right ventricle may be affected probably in part by the increased afterload from lung disease, with or without clots, and partly in some patients by concomitant inflammation in not only the left ventricle but the right ventricle," he said.

"And if the right ventricle is impaired in terms of its function, that's not good, but whether there is long-term damage will require further studies."

Huang and colleagues had no disclosures. Argulian and all his coauthors disclose that they have no relevant conflicts. Goldstein is founder and has ownership interest in ECLS Inc, in relation to which he also holds intellectual property rights or patents.

JACC Cardiovasc Imaging. Published online May 11, 2020 and May 15, 2020.


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