What is the clinical evidence from this study?

Study design: Observational. Population: COVID-19 (n=77). Intervention: Cardiac fibrosis (assessed by left ventricular global longitudinal strain) vs. Patients without severe COVID-19. Primary outcome: Prediction of severe COVID-19 disease course using left ventricular global longitudinal strain (AUC 0.9167, 95% CI 0.7481-1.0, p=0.0225).

October 22, 2021Open Access

Cardiac Fibrosis Is a Risk Factor for Severe COVID-19

Key Result

Left ventricular global longitudinal strain, an echocardiographic marker of cardiac fibrosis, accurately predicted the development of severe COVID-19 in patients presenting to the emergency department (AUC 0.9167).

Study Design

Type

Observational (n=77)

Multicenter

Structured PICO

Does pre-existing cardiac fibrosis predict severe disease progression in COVID-19 patients?

Population

77 adults (age ≥18 years) presenting to the emergency department with signs of acute respiratory infection, including 36 with COVID-19 (23 moderate, 13 severe) and 41 controls with non-SARS-CoV-2 respiratory infections. The study also included left ventricular autopsy tissue from deceased COVID-19 patients.

Comparator

Patients with non-SARS-CoV-2 respiratory infections (controls) and patients with moderate COVID-19 disease

Outcome

COVID-19 disease severity (severe disease defined as need for mechanical ventilation, ICU admission, or death) and levels of cardiac fibrosis markers (TGF-β1 mRNA, left ventricular global longitudinal strain)surrogate

Pre-existing cardiac fibrosis, indicated by elevated blood TGF-β1 mRNA and abnormal left ventricular global longitudinal strain, is a risk factor for severe COVID-19 progression.

Main Result

Effect estimate: AUC 0.9167 (95% CI 0.7481-1.0)

p-value: p=0.0225

Limitations

Myocardial biopsies from patients with mild to moderate disease could not be included for ethical reasons.
Increased myocardial strain is only an indirect measure of cardiac fibrosis.
Financial expense of detecting fibrosis via cardiac MRI in patients with severe disease was a limiting factor.
Cannot completely exclude the presence of macroscopically invisible focal myocarditis.
Discrepancy between NRP-1 expression and absence of SARS-CoV-2 virus in cardiac samples.

Abstract

Increased left ventricular fibrosis has been reported in patients hospitalized with coronavirus disease 2019 (COVID-19). It is unclear whether this fibrosis is a consequence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection or a risk factor for severe disease progression. We observed increased fibrosis in the left ventricular myocardium of deceased COVID-19 patients, compared with matched controls. We also detected increased mRNA levels of soluble interleukin-1 receptor-like 1 (sIL1-RL1) and transforming growth factor β1 (TGF-β1) in the left ventricular myocardium of deceased COVID-19 patients. Biochemical analysis of blood sampled from patients admitted to the emergency department (ED) with COVID-19 revealed highly elevated levels of TGF-β1 mRNA in these patients compared to controls. Left ventricular strain measured by echocardiography as a marker of pre-existing cardiac fibrosis correlated strongly with blood TGF-β1 mRNA levels and predicted disease severity in COVID-19 patients. In the left ventricular myocardium and lungs of COVID-19 patients, we found increased neuropilin-1 (NRP-1) RNA levels, which correlated strongly with the prevalence of pulmonary SARS-CoV-2 nucleocapsid. Cardiac and pulmonary fibrosis may therefore predispose these patients to increased cellular viral entry in the lung, which may explain the worse clinical outcome observed in our cohort. Our study demonstrates that patients at risk of clinical deterioration can be identified early by echocardiographic strain analysis and quantification of blood TGF-β1 mRNA performed at the time of first medical contact.

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