In COVID-19 Without HF, High NT-proBNP Predicts Mortality

October 14, 2020

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Mortality goes up in tandem with admission natriuretic peptide levels in patients with severe COVID-19 pneumonia but no history of heart failure (HF), perhaps signaling a need for careful fluid management and other cardioprotective measures, researchers propose, on the basis of their single-center study.

The findings, which highlight the biomarker's value in COVID-19 outside its usual realm of HF diagnosis and risk assessment, suggest it might have a potential role in determining treatment goals. Elevated levels, for example, might help in identifying whether a patient's dyspnea or other symptoms are a temporary part of the acute viral syndrome, or rather the result of actual myocardial injury from SARS-CoV-2, they speculate.

One-month mortality was about 38% for patients with admission levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) at the median or higher, and about 10% for those with below-median levels. Risk climbed continuously with rising levels of the biomarker (< .001). The likelihood of death or mechanical ventilation also went up with higher NT-proBNP levels, but the effect was less strongly significant.

Although the physiologic cause or causes of NT-proBNP elevation in such patients is unclear, it could reflect viral injury to the heart or, perhaps, a transient vulnerability to volume overload that leads to symptoms, Andreas P. Kalogeropoulos, MD, MPH, PhD, told | Medscape Cardiology. "There may be two different phenotypes."

It's common to administer large amounts of fluids to admitted patients who are febrile with an apparent respiratory infection, Kalogeropoulos observed. But, he speculated, in some such patients — their heart, kidneys, and lungs weakened from the infection — even slight volume overload "that most people would handle nicely may be causing an exaggeration of symptoms and the actual pathology," he said.

Elevated NT-proBNP, he said, "may be an indicator that these patients need to be rehydrated really carefully, with monitoring of their status clinically," and followed with repeat NT-proBNP assays to see whether levels go up or down with management. "That's our hypothesis."

Kalogeropoulos is senior author on the study presented October 3 at the Heart Failure Society of America (HFSA) Virtual Annual Scientific Meeting 2020 by lead author Jeanwoo Yoo, MD. Both are from Renaissance School of Medicine at Stony Brook University, New York.

"Because elevated NT-proBNP may be an underlying indicator of patients more prone to developing volume overload and congestion," Yoo told | Medscape Cardiology, "we're looking at whether it can predict how much diuretics a patient might need throughout their admission."

It's unclear whether elevated natriuretic peptides in patients with COVID-19 necessarily reflect cardiac dysfunction and congestion, agreed James L. Januzzi Jr, MD, Harvard University and Massachusetts General Hospital, Boston, who isn't connected to the current study. Elevated levels aren't necessarily caused only by myocardial "stretch" from overload, as often depicted in the literature. They can signal any of a wide range of cardiac conditions, including exposure to "the cytokine storm that occurs in somebody with severe critical illness," he told | Medscape Cardiology.

But the study's association of elevated NT-proBNP with mortality isn't a surprise, Januzzi said. From the very first reports from Asia to the present day, "cardiac biomarkers, including natriuretic peptides, have been significantly associated with poor outcomes in patients with SARS-CoV-2 infection."

Also, the current study with only about 300 patients is underpowered for any definitive conclusions, he said. "Another limitation is that they don't have serial measurements. Some studies have shown that the value for NT-proBNP on admission is far less informative than if you measure it each day and look for a trend. Rising values are strongly associated with risk for adverse outcome."

It's increasingly common for centers to measure both natriuretic peptides and troponins in their patients with COVID-19, "but the question ultimately gets down to, what do you do with the results? Does this change what we do for our patients?" asked Januzzi, referring to the larger issue addressed by Kalogeropoulos and Yoo.

"I think that it does, but it requires some out-of-the-box thinking. If NT-proBNP is elevated, it's important for clinicians not to jump at a diagnosis of heart failure," he said. Understanding that elevated NT-proBNP in COVID-19 "does not equal heart failure" is important for management decisions.

For example, treatment aimed at HF in patients like those in the current study "might be appropriate if the clinical picture is that of heart failure. But importantly, it could also create troubles if you're treating a patient with diuretic who actually does not have heart failure," Januzzi said.

The current analysis looked at 303 adults without a history of HF who were admitted for severe COVID-19 pneumonia from March 1 through April 15; it excluded those who were intubated or died within the first 24 hours, the group reports.

Those with admission NT-proBNP levels of at least 156 ng/L, the median, were older and had more atrial fibrillation (AF) and a lower body mass index (BMI) (P < .001 for all three differences).

Overall mortality after a median of 12 days was 24.3%, and 19.4% were intubated and survived to hospital discharge.

Outcomes by Admission NT-proBNP Level, ≥156 ng/L vs <156 ng/L)
End Point NT-proBNP ≥156 ng/L (n = 151) NT-proBNP <156 ng/L (n = 152) P Value
28-d mortality* (%) 38.4 10.5 <.001
28-d death or mechanical ventilation (%) 50.3 37.5 .040
Non-ICU hospital days (d) 7 9 .027
Length of hospitalization (d) 13 12 .59
*Primary end point

The mortality hazard ratio (HR) for every doubling of admission NT-proBNP level was 1.29 (95% CI, 1.17 - 1.43; P < .001), after adjustment for demographics, diabetes, coronary artery disease, AF, BMI, and baseline O2 saturation. The HR was 1.09 (95% CI, 1.01 - 1.18; P = .025) for the composite secondary end point of death or mechanical ventilation.

Kalogeropoulos said the findings were largely confirmed in a much larger cohort of such patients from his center, about 900 adults; those results are under submission for publication.

Levels of cardiac biomarkers, including NT-proBNP, in patients with severe COVID-19 can help in deciding whether to perform imaging in individual patients, Januzzi noted. If they are normal, "and there's no other clear indication of cardiac dysfunction, referring that patient for cardiac imaging is probably not fruitful."

But if the clinical picture "is consistent with the need for further evaluation" — for example, if the patient is showing signs of shock — elevated NT-proBNP levels, especially if they are markedly elevated, "may help to direct one toward some type of next-step imaging," such as point-of-care ultrasound.

Kalogeropoulos and Yoo had no disclosures. Januzzi discloses receiving grant support from Novartis, Applied Therapeutics, and Innolife; consulting for Abbott Diagnostics, Janssen, Novartis, Quidel, and Roche Diagnostics; and serving on end point committees or data safety monitoring boards for trials supported by Abbott, AbbVie, Amgen, CVRx, Janssen, MyoKardia, and Takeda.

Heart Failure Society of America Virtual Annual Scientific Meeting 2020: Abstract 202. Presented October 3, 2020.

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