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Right Ventricular Abnormality in Patients Hospitalized With COVID-19 Infection During Omicron Variant Surge

      Echocardiographic changes in the acute phase of COVID-19 infection have been extensively reported during the COVID-19 pandemic. Measures of right ventricular (RV) performance during acute infection have been associated with mortality.
      • Omar A
      • De La Cruz
      • Tejada A
      • Ronderos D
      • Hernandez N
      • Miranda J
      • Rehmani A
      • Nicu M
      • Chilimuri S
      • Bella JN.
      Echocardiography derived predictors of worse outcomes in the acute phase of COVID-19 patients compared to matched controls.
      • Argulian E
      • Sud K
      • Vogel B
      • Bohra C
      • Garg VP
      • Talebi S
      • Lerakis S
      • Narula J.
      Right ventricular dilation in hospitalized patients with COVID-19 infection.
      • Diaz-Arocutipa C
      • Saucedo-Chinchay J
      • Argulian E.
      Association between right ventricular dysfunction and mortality in COVID-19 patients: a systematic review and meta-analysis.
      We aimed at studying the association of in-hospital mortality with echocardiographic measures of RV performance during the COVID-19 infection surge in New York City attributed to the spread of the Omicron variant.
      • Argulian E
      • Sud K
      • Vogel B
      • Bohra C
      • Garg VP
      • Talebi S
      • Lerakis S
      • Narula J.
      Right ventricular dilation in hospitalized patients with COVID-19 infection.
      In this retrospective study, we enrolled consecutive patients hospitalized with COVID-19 infection who underwent clinically indicated echocardiograms from December 15, 2021, to January 26, 2022. Omicron became the predominant strain in the United States in December 2021 and accounted for >99% of COVID-19 cases. Echocardiograms were performed adhering to a focused, time-efficient protocol with appropriate use of personal protective equipment and limited viral exposure time. Portable ultrasound machines were used: CX50 (Philips Medical Systems, Bothell, Washington) and Vivid S70 (GE Healthcare Systems, Milwaukee, Wisconsin). Echocardiographic studies were interpreted by experienced echocardiography attending physicians. RV abnormality was defined as basal RV diastolic diameter >4.1 cm in the RV-focused apical view and/or tricuspid annular plane systolic excursion <1.7 cm from the apical 4-chamber view. The primary end point was in-hospital mortality. Kaplan-Meier curves and Cox regression analysis were used to explore the associations of clinical and echocardiographic predictors with in-hospital mortality. The study protocol was approved by the Institutional Review Board.
      Echocardiograms of 122 consecutive patients were reviewed. The mean age was 69 ± 14.5 years, and 62 patients (51%) were women. Thirty-seven patients (30%) were admitted to the intensive care unit, and 25 (21%) were intubated and mechanically ventilated at the time of the echocardiographic examination. The mean RV diastolic diameter was 3.5 ± 0.78 cm, with >4.1 cm in 27 patients (22%). The mean tricuspid annular plane systolic excursion was 2.1 ± 0.5 cm with <1.7 cm in 22 patients (18%). Despite consideration of the Omicron strain as a milder variant, 41 patients (34%) had RV dysfunction, comparable with previous reports of COVID-19 infections with earlier strains. Patients with and without RV abnormality did not differ significantly in age, gender, body mass index, major cardiovascular co-morbidities, and COVID-19 vaccination status. There were also no significant differences in the admission values of white blood cell count, C-reactive protein, serum creatinine, d-dimer levels, or serum lactate levels. However, patients with RV abnormality had higher serum troponin I levels (1.5 ± 5.5 vs 0.25±0.8 ng/mL, p=0.048). There were no differences between groups in the use of therapeutic anticoagulation (68% vs 71%, p = 0.8) or corticosteroid therapy (61% vs 53%, p = 0.38). Patients with RV abnormality had lower left ventricular ejection fraction (52 ± 14 vs 58 ± 10%, p = 0.012; 29% vs 14% with EF <50%, p = 0.046), and greater left atrial volume index (40 ± 22 vs 32 ± 15 ml/m2, p = 0.03) and tricuspid regurgitation velocity (2.5 ± 0.7 vs 2.2 ± 0.7 m/s, p = 0.019). By the end of study, 19 patients (16%) had died; 11 (27%) with RV abnormality and 8 (10%) without RV dysfunction, p = 0.019 (Figure 1). Univariate Cox regression analysis showed that age (hazards ratio [HR] 1.04, p = 0.037, 95% confidence interval [CI] 1.003 to 1.1), admission troponin I level (HR 1.2, p <0.001, 95% CI 1.08 to 1.28), and mechanical ventilation (HR 16.1, p <0.001, 95% CI 5.34 to 48.7) were clinical variables associated with in-hospital mortality. The mean e' velocity (HR 0.76, p = 0.008, 95% CI 0.62 to 0.931), tricuspid regurgitation velocity >2.8 m/s (HR 3.1, p = 0.024, 95% CI 1.16 to 8.04), and RV abnormality (HR 2.51, p = 0.047, 95% CI 1.01 to 6.25) were echocardiographic variables associated with in-hospital mortality, although left ventricular ejection fraction was not associated with the outcome. After adjusting for the clinical variables (age, troponin I level, and mechanical ventilation), only RV abnormality remained associated with in-hospital mortality (HR 3.1, p = 0.032, 95% CI 1.1 to 8.8).
      Figure 1
      Figure 1Echocardiographic predictors of in-hospital mortality. (A) Kaplan-Meier curve showing worse in-hospital mortality in patients with RV abnormality compared with patients without RV dysfunction. (B) Hazard ratios for echocardiographic predictors of mortality adjusted for age, mechanical ventilation, and admission troponin I levels. TRV = tricuspid regurgitation velocity.
      This study confirms that RV abnormality remained prevalent in hospitalized patients with COVID-19 infection during the Omicron surge in New York City. RV abnormality was strongly and independently associated with in-hospital mortality. Prospective studies should elucidate the role of therapeutic interventions on the measures of RV performance in these patients.

      Disclosures

      The Adolfo García-Sastre laboratory has received research support from Pfizer, Senhwa Biosciences, Kenall Manufacturing, Avimex, Johnson & Johnson, Dynavax, 7 Hills Pharma, Pharmamar, ImmunityBio, Accurius, nanoComposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharmaceuticals and Merck, outside of the reported work. Dr. García-Sastre has consulting agreements for the following companies involving cash and/or stock: Vivaldi Biosciences, Contrafect Corporation, 7 Hills Pharma, Avimex, Vaxalto, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, Paratus, CureLab Oncology, CureLab Veterinary, Synairgen, and Pfizer, outside of the reported work. Dr. García-Sastre is the inventor of patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. The other authors have no conflicts of interest to declare.

      Acknowledgments

      This work was partly supported by CRIPT (Center for Research on Influenza Pathogenesis and Transmission), a National Institute of Allergy and Infectious Diseases (NIAID)-funded Center of Excellence for Influenza Research and Response (CEIRR, contract No. 75N93021C00014), and by an NCI (National Cancer Institute) grant U54CA260560 (to AG-S).

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