Right ventricular (RV) abnormalities are the most common echocardiographic findings in acute COVID-19.1 , 2 While RV dysfunction is associated with in-hospital mortality in acute COVID-19,3 , 4 the prognostic implications of RV dilation alone are less clear. Similarly, little is known about the clinical significance of RV dilation and dysfunction among patients hospitalized with acute COVID-19 compared with other respiratory illnesses, such as bacterial pneumonia. We studied the association of RV dilation and dysfunction with in-hospital mortality in acute COVID-19 compared with bacterial pneumonia.
A retrospective cohort study design was utilized to compare 225 consecutive adults admitted for acute COVID-19 between March 2020 and February 2021 at UCSF Health and Zuckerberg San Francisco General Hospital with 257 control hospitalizations for bacterial pneumonia. To be included, all patients had to have a clinically ordered transthoracic echocardiogram (TTE) during hospitalization. COVID-19 was diagnosed by polymerase chain reaction, while cases of bacterial pneumonia were included based on International Classification of Diseases codes. Qualitative measurements of RV size and function were extracted from the echo report of the first TTE performed after admission. We constructed logistic regression models to estimate associations between RV dilation, RV dysfunction, and in-hospital mortality while adjusting for age, sex, body mass index (BMI), medical history, admission estimated glomerular filtration rate, hemoglobin, and presence of mechanical ventilation and used postestimation to estimate adjusted relative risks. Fine and Gray competing-risks regression models treating discharged alive as a competing risk were implemented to estimate the effect of RV dilation on mortality.
Individuals in the COVID-19 cohort were younger, and more identified as Hispanic compared with the bacterial pneumonia group (Table 1 ). Body mass index was higher in the COVID-19 group, and there was a higher prevalence of cancer, chronic obstructive pulmonary disease, and atrial fibrillation in the bacterial pneumonia group. Compared with those hospitalized with bacterial pneumonia, patients with acute COVID-19 were more likely to be managed in the intensive care unit, require mechanical ventilation, be initiated on renal replacement therapy, develop a venous thromboembolism, and have a longer length of stay.
Table 1.
Baseline characteristics of individuals hospitalized with COVID-19 or bacterial pneumonia who underwent a clinically indicated TTE
| Variable | COVID | Bacterial pneumonia | P value |
|---|---|---|---|
| N | 225 | 257 | |
| Age, years, mean ± SD | 62.9 ± 16.7 (n = 225) | 67.5 ± 17.4 (n = 257) | .003 |
| Sex: | .07 | ||
| Male | 148 (65.8) | 148 (57.6) | |
| Female | 77 (34.2) | 109 (42.4) | |
| Race/ethnicity: | <.001 | ||
| Hispanic/Latinx | 85 (38.1) | 29 (11.3) | |
| Native American/Alaska native | 3 (1.3) | 1 (0.4) | |
| Non-Hispanic Black/African American | 22 (9.9) | 25 (9.7) | |
| Non-Hispanic White | 42 (18.8) | 110 (42.8) | |
| Asian | 44 (19.7) | 79 (30.7) | |
| Native Hawaiian or Pacific Islander | 7 (3.1) | 2 (0.8) | |
| Other Non-Hispanic | 20 (9.0) | 11 (4.3) | |
| BMI, mean ± SD | 29.4 ± 8.1 | 26.7 ± 7.8 | <.001 |
| Hypertension | 100 (44.4) | 107 (41.6) | .53 |
| Diabetes | 53 (23.6) | 52 (20.2) | .38 |
| Dyslipidemia | 40 (17.8) | 55 (21.4) | .32 |
| Heart failure prior to admission | 14 (6.2) | 23 (8.9) | .26 |
| Prior coronary artery bypass graft | 1 (0.4) | 1 (0.4) | .92 |
| Prior heart attack | 4 (1.8) | 2 (0.8) | .32 |
| Prior percutaneous coronary intervention | 5 (2.3) | 1 (0.4) | .07 |
| Prior atrial fibrillation | 12 (5.3) | 31 (12.1) | .01 |
| Prior stroke/transient ischemic attack | 18 (8.0) | 17 (6.6) | .56 |
| Cancer | 37 (16.4) | 82 (31.9) | <.001 |
| Prior deep vein thrombosis | 5 (2.2) | 11 (4.3) | .21 |
| Prior pulmonary embolism | 4 (1.8) | 17 (6.6) | .009 |
| Chronic kidney disease | 25 (11.1) | 30 (11.7) | .89 |
| On dialysis prior to admission | 5 (2.2) | 3 (1.2) | .37 |
| Solid organ transplant | 9 (4.0) | 8 (3.1) | .6 |
| HIV | 4 (1.8) | 3 (1.2) | .71 |
| Chronic obstructive pulmonary disease | 8 (3.6) | 33 (12.8) | <.001 |
| Asthma | 13 (5.8) | 24 (9.3) | .14 |
| Patient managed in intensive care unit | 170 (75.6) | 97 (37.7) | <.001 |
| Mechanical ventilation during hospitalization | 121 (53.8) | 38 (14.8) | <.001 |
| Initiation of hemodialysis/continuous renal replacement therapy | 21 (9.3) | 3 (1.2) | <.001 |
| Deep vein thrombosis or pulmonary embolism during hospitalization | 57 (25.3) | 29 (11.3) | <.001 |
| Length of stay in days, median (interquartile range) | 20.0 (10.0, 34.0) | 8.0 (5.0, 13.0) | <.001 |
| Days to echo, median (interquartile range) | 2.0 (1.0, 5.0) | 2.0 (1.0, 3.0) | .50 |
| Intubated at echo | 70 (31.1) | 22 (8.6) | <.001 |
| LV ejection fraction, mean ± SD | 60.4 ± 12.7 (n = 203) | 59.7 ± 12.2 (n = 232) | .56 |
| Reduced LV function (<50%) | 30 (14.8) | 36 (15.5) | .83 |
| LV longitudinal strain, mean ± SD | −18.2 ± 4.0 (n = 30) | −17.7 ± 4.1 (n = 21) | .66 |
| RV volume: | .99 | ||
| Normal | 164 (77.7) | 183 (77.2) | |
| Borderline | 9 (4.3) | 9 (3.8) | |
| Mildly reduced | 19 (9.0) | 25 (10.5) | |
| Mild to moderately reduced | 5 (2.4) | 6 (2.5) | |
| Moderately reduced | 9 (4.3) | 8 (3.4) | |
| Moderate to severely reduced | 1 (0.5) | 1 (0.4) | |
| Severely reduced | 4 (1.9) | 5 (2.1) | |
| RV dilated: | .91 | ||
| Normal RV size | 165 (77.8) | 183 (77.2) | |
| Dilated RV | 47 (22.2) | 54 (22.8) | |
| RV function: | .078 | ||
| Normal | 187 (87.4) | 200 (87.0) | |
| Borderline | 3 (1.4) | 0 (0.0) | |
| Mildly reduced | 17 (7.9) | 23 (10.0) | |
| Mild to moderately reduced | 3 (1.4) | 7 (3.0) | |
| Moderately reduced | 3 (1.4) | 0 (0.0) | |
| Moderate to severely reduced | 1 (0.5) | 0 (0.0) | |
| Reduced RV function: | 1 | ||
| Normal RV function | 187 (87.4) | 200 (87.0) | |
| Reduced RV function | 27 (12.6) | 30 (13.0) | |
| Tricuspid annular plane systolic excursion, cm, mean ± SD | 2.3 ± 1.0 (n = 199) | 2.3 ± 1.4 (n = 251) | .74 |
| RV S’ velocity, mean ± SD | 14.3 ± 4.2 (n = 92) | 13.6 ± 3.8 (n = 121) | .2 |
| TR peak gradient, mean ± SD | 31.5 ± 13.5 (n = 103) | 35.3 ± 15.5 (n = 164) | .020 |
| TR peak gradient elevated | 32 (35.2) | 85 (51.8) | .01 |
| Estimated RV systolic pressure, mm Hg, mean ± SD | 35.7 ± 14.4 (n = 89) | 40.6 ± 16.3 (n = 164) | .02 |
| Estimated right atrial pressure, mm Hg, mean ± SD | 4.6 ± 3.6 (n = 119) | 5.3 ± 4.1 (n = 192) | .09 |
Data in parentheses are percentages unless otherwise specified. T tests were used for normally distributed continuous variables, chi-squared for categorical, and Wilcoxon rank-sum for skewed continuous data. LV = Left ventricular.
There was a similar prevalence of qualitative RV dilation (22.2% vs 22.8%, P = .91) and RV dysfunction (12.6% vs 13.0%, P = 1.00) in both groups. Similarly, the mean tricuspid annular plane systolic excursion and RV s’ were comparable between the 2 groups. Peak tricuspid regurgitation (TR) gradient and estimated RV systolic pressure were higher among those with bacterial pneumonia, despite higher use of mechanical ventilation among those with COVID-19.
Those hospitalized with COVID-19 had a higher risk of inpatient mortality compared with the bacterial pneumonia group (adjusted relative risk = 2.00; 95% CI, 1.28-3.14). Compared with those with bacterial pneumonia and normal RV size (Figure 1 ), the adjusted relative risk for in-hospital mortality among those with bacterial pneumonia and RV dilation was 1.09 (95% CI, 0.47-2.57; P = .84); COVID-19 and normal RV size, 1.88 (1.05-3.37; P = .03); and COVID-19 with RV dilation, 3.02 (95% CI, 1.52-6.01; P = .002).
Figure 1.
Fine and Gray competing-risks regression model adjusted for age, sex, BMI, medical history, admission estimated glomerular filtration rate, hemoglobin, and presence of mechanical ventilation. The reference group used was those with bacterial pneumonia with normal RV size.
To our knowledge, this study is one of the first to compare the clinical significance of RV dilation in acute COVID-19 compared with other respiratory illnesses. We found that RV dilation was associated with in-hospital mortality among patients hospitalized with acute COVID-19 but not among those hospitalized with bacterial pneumonia. Consistent with our findings, in prior studies of adults admitted for H1N1 influenza, RV dilation and dysfunction were common echo findings, but neither was associated with mortality.5 , 6 Our finding that RV dysfunction is not associated with mortality is discordant with the literature.7
Right ventricular dilation may be associated with mortality in COVID-19 due to the severity of the pulmonary pathology or due to SARS-CoV-2 infection independent of its effects in the lungs. Although the COVID-19 group had a higher mortality rate than the bacterial pneumonia group, there was a similar prevalence of RV dilation and RV dysfunction in both groups, which points toward an unidentified culprit for higher mortality beyond acute RV stress from hypoxic vasoconstriction. Interestingly, those with bacterial pneumonia had a higher TR peak gradient and estimated RV systolic pressure despite lower rates of pulmonary emboli and mechanical ventilation compared with the COVID-19 group, suggesting that the etiology of RV dilation may not correlate directly to elevated pulmonary artery pressures in hypoxic pulmonary disease. Differences in the inflammatory response to SARS-CoV-2 resulting in shunt physiology could increase RV volume overload, or perhaps the RV is more sensitive to microvascular dysfunction from coronary endotheliitis.
Limitations of this largely retrospective study include using electronic health records, which carries a risk of misclassification and confounding. Sampling bias likely occurred as we only included patients who received a clinically indicated echo; thus a sicker patient population may have been selected. While we mainly focused on qualitative measurements of RV size and function, manual measurement of RV was technically limited in clinical echocardiograms obtained in the critically ill. We did not classify the severity of illness in either group. Finally, this cohort reflects the inpatient experience of earlier variants among largely unvaccinated individuals.
Acknowledgments
We thank the UCSF Clinical and Translational Science Institute for assistance in the collection of clinical patient data, including laboratory and imaging results.
Footnotes
Conflicts of Interest: None.
This publication was supported by the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through UCSF-CTSI grant no. UL1 TR001872. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. This study and Dr. Durstenfeld were supported by NIH/National Heart, Lung, and Blood Institute grant no. K12 HL143961. Dr. Parikh was supported by a UC Office of the President grant (R00RG2986).
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