†These authors contributed equally.
To investigate the right heart function in coronavirus disease 2019 (COVID-19)
patients with acute respiratory distress syndrome (ARDS), a retrospective
analysis of 49 COVID-19 patients with ARDS was performed. Patients were divided
into severe group and critically-severe group according to the severity of
illness. Age-matched healthy volunteers were recruited as a control group. The
cardiac cavity diameters, tricuspid annular plane systolic excursion (TAPSE),
tricuspid valve regurgitation pressure gradient biggest (TRPG), pulmonary
arterial systolic pressure (PASP), maximum inferior vena cava diameter (IVCmax)
and minimum diameter (IVCmin), and inferior vena cava collapse index (ICV-CI)
were measured using echocardiography. We found that the TAPSE was significantly
decreased in pneumonia patients compared to healthy subjects (P
Coronavirus disease 2019 (COVID-19) pneumonia, caused by the SARS coronavirus 2 (SARS-CoV-2), has spread rapidly all over the world (Q. Li et al., 2020; WHO, 2020). This disease can induce systemic multiple organ damage, especially in the lungs (Wu and McGoogan, 2020). Yang et al. (2020) reported that 26.1% of patients required admission to an intensive care unit (ICU) and 61.1% developed acute respiratory distress syndrome (ARDS). Moreover, 81% of patients who died from COVID-19 developed ARDS, compared to 45% in those who survived COVID-19 (D. Wang et al., 2020).
Previous research shows that ARDS is often accompanied by right ventricular (RV) dysfunction and the incidence is between 20-30% (Boissier et al., 2013; Mekontso Dessap et al., 2016; Repesse et al., 2016). RV dysfunction is an important determinant of mortality in ARDS patients. However, the incidence of RV dysfunction in patients with ARDS caused by COVID-19 pneumonia is unclear. At present, echocardiography is the preferred choice for evaluating RV function of patients with ARDS, because it is delivered at the bedside, and it is non-invasive and convenient. Tricuspid annular plane systolic excursion (TAPSE) is widely used as a quantitative index to evaluate RV function, which is highly correlated with the mortality of ARDS patients, thus providing a good parameter for to interpret RV function in COVID-19 patients (Wadia et al., 2016).
In this study, we sought to determine the incidence of RV dysfunction using echocardiography in a cohort of patients with ARDS caused by COVID-19 pneumonia.
Healthy (n = 25) | Severe patients (n = 35) | critically-severe (n = 14) | |
Male | 12 (48.0%) | 19 (54.3%) | 6 (42.9%) |
Age | 62.2 |
64.3 |
65.6 |
HR | 72.5 |
77.4 |
88.0 |
MAP | 76.5 |
90.7 |
78.1 |
APACHE II | - | 6.2 |
15.1 |
Mechanical ventilation | - | - | 11 (78.6%) |
Invasive ventilation | - | 0 | 14 (100%) |
Non-invasive ventilation | - | 26 (74.3%) | 0 |
PEEP (cmH |
- | 5.8 |
13.1 |
Vasoactive agent | - | - | 8 (57.1%) |
PaO |
- | 189.1 |
92.3 |
ARDS | |||
Mild | - | 22 (62.9%) | - |
Moderate | - | 13 (37.1%) | 4 (28.6%) |
Severe | - | - | 10 (71.4%) |
Co-morbidities | |||
Hypertension | - | 12 (34.3%) | 5 (35.7%) |
Diabetes | - | 8 (22.9%) | 5 (35.7%) |
Cardiovascular disease | - | 6 (17.1%) | 2 (14.3%) |
Note: HR: heart rate; MAP: mean arterial pressure; APACHE II:
Acute Physiology and Chronic Health Evaluation II; ARDS: acute respiratory
distress syndrome. *P |
We retrospectively analyzed 49 patients (age
Values of TAPSE (A), PASP (B), PAD (C) and ICV-CI (D) for
individual patients with COVID-19 pneumonia and healthy subjects. The dotted
line in (A) indicates 17 mm of TAPSE. TAPSE: tricuspid annular plane
systolic excursion; PASP: pulmonary arterial systolic pressure; PAD: pulmonary
artery diameter; ICV-CI: inferior vena cava collapse index. *P
Echocardiography assessment was performed in all patients within 48 h of ICU admission by the same echocardiographer using a commercially available system (Vivid E9, GE, Inc.) equipped with a 2.5-4 MHz transducer (M5S probe). All patients were examined in a calm or sedated state. All echocardiographic parameters were evaluated according to the guidelines of American Society of Echocardiography (ASE) (Lang et al., 2015).
TAPSE was defined as the peak excursion of tricuspid annulus from end-diastole to end-systole and was measured from the apical four-chamber view by placing a M-mode cursor through the lateral tricuspid annulus. The TAPSE less than 17 mm indicates RV dysfunction (Lang et al., 2015).
The diameter changes of inferior vena cava (IVC) during the respiratory cycle
were measured from the IVC long axis view by M-mode. When breathing
spontaneously, the minimum diameter of the inferior vena cava (IVCmin) was
measured in the inspiratory phase and the maximum diameter of the inferior vena
cava (IVCmax) was measured in the expiratory phase. The inferior vena cava
collapse index (ICV-CI) was calculated by the formula of (IVCmax-IVCmin) / IVCmax
The diameter of pulmonary artery (PAD) was measured from parasternal short-axis view by two-dimensional echocardiography. Tricuspid valve regurgitation pressure gradient biggest (TRPG) was measured and pulmonary arterial systolic pressure (PASP) was estimated indirectly by tricuspid regurgitation velocity with the addition of right atrial pressure, assuming no significant right ventricular outflow tract (RVOT) obstruction.
By two-dimensional echocardiography, left ventricular end-diastolic dimension (LVEDD) was measured from the parasternal long-axis view, while the right atrial diameter (RAD) and right ventricular diameter (RVD) were measured from the apical four-chamber view. The sampling volume was placed above the aortic valve orifice to obtain the aortic valve blood flow spectrum and measure the aortic valve velocity (AV) from the apical five-chamber view. A modified Simpson’s method was used to measure left ventricular end-diastolic volume (EDV) and end-systolic volume (ESV). Left ventricular ejection fraction (LVEF) was calculated as followed: LVEF = (EDV-ESV) / EDV.
The statistical analysis was performed using GraphPad Prism 6. Categorical
variables are reported as frequencies and percentages. Continuous variables were
reported as mean
Among all patients enrolled, 35 (71.4%) were classified under the severe type of COVID-19 pneumonia and 14 (28.6%) were classified under the critically-severe type. There were 22 (62.9%) patients with mild and 13 (37.1%) with moderate ARDS in the severe patients, four (28.6%) with moderate, and 10 (71.4%) with severe ARDS in critically-severe patients. The clinical characteristics of patients are shown in (Table 1).
There was no significant difference in age and biological sex between COVID-19
pneumonia patients and healthy donors (P
Healthy (n = 25) | Severe patients (n = 35) | critically-severe (n = 14) | |
PAD (mm) | 20.2 |
23.7 |
25.3 |
TRPG (mmHg) | - | 25.3 |
28.8 |
PASP (mmHg) | - | 29.8 |
35.9 |
TAPSE (mm) | 23.8 |
20.4 |
17.6 |
IVCmax (mm) | 14.4 |
14.0 |
17.6 |
IVCmin (mm) | 7.7 |
6.2 |
12.1 |
ICV-CI (%) | 50.4 |
55.9 |
34.1 |
Note: PAD: pulmonary artery diameter; TRPG: tricuspid valve
regurgitation pressure gradientbiggest; PASP: pulmonary arterial systolic
pressure; TAPSE: tricuspid annular plane systolic excursion; IVCmax: maximum
diameter of the inferior vena cava; IVCmin: minimum diameter of the inferior vena
cava; ICV-CI: inferior vena cava collapse index. *P |
Values of TAPSE for individual subjects are shown in (Fig. 1A). A normal TAPSE
was recorded in all healthy subjects, and the TAPSE was significantly decreased
in patients with COVID-19 pneumonia. Further, the TAPSE was significantly lower
in critically-severe patients than in severe patients (P = 0.0128).
Three (8.6%) severe and five (35.7%) critically-severe patients had a reduced
TAPSE (
The echocardiographic parameters of RV function in patients with COVID-19
pneumonia are shown in (Table 2) and (Fig. 1B-D). Tricuspid regurgitation
was present in 21 (60.0%) severe and 13 (92.9%) critically-severe patients, and
there were no statistically significant differences in PASP and TRPG between the
two groups (P
Healthy (n = 25) | Severe patients (n = 35) | critically-severe (n = 14) | |
LVEDD (mm) | 43.6 |
45.6 |
44.3 |
RVD (mm) | 17.6 |
34.7 |
34.6 |
RAD (mm) | 30.4 |
32.7 |
34.1 |
LVEF (%) | 64.8 |
63.9 |
59.4 |
AV (cm/s) | 117.4 |
112.7 |
112.1 |
Note: LVEDD: left ventricular end-diastolic dimension; RVD:
right ventricular diameter; RAD: right atrial diameter; LVEF: left ventricular
ejection fraction; AV: aortic valve velocity. *P |
The diameters of cardiac cavity and other echocardiographic parameters are shown
in (Table 3). Patients with COVID-19 pneumonia had significantly larger right
atrium and right ventricle than healthy subjects (P
There were 22 patients with mild, 17 with moderate and 10 with severe ARDS in the selected COVID-19 pneumonia population. The clinical characteristics and echocardiographic parameters in COVID-19 pneumonia patients being classified by ARDS severity are shown in (Table 4).
Severe ARDS patients had significantly higher APACHE II score and lower
PaO
Healthy (n = 25) | Mild (n = 22) | Moderate (n = 17) | Severe (n = 10) | |
Male | 12 (48.0%) | 12 (54.5%) | 9 (52.9%) | 4 (40.0%) |
Age | 62.2 |
67.1 |
60.2 |
66.8 |
HR | 72.5 |
79.0 |
74.8 |
93.00 |
MAP | 76.5 |
93.6 |
84.6 |
77.0 |
APACHE II | - | 6.2 |
6.9 |
17.4 |
Mechanical ventilation | ||||
Invasive ventilation | - | 0 | 4 (23.5%) | 10 (100%) |
Non-invasive ventilation | - | 13 (59.1%) | 13 (76.5%) | 0 |
PEEP (cmH |
4.8 |
7. 5 |
14.4 | |
PaO |
- | 214.7 |
143.1 |
75.7 |
Co-morbidities | ||||
Hypertension | - | 7 (31.8%) | 6 (35.3%) | 4 (40.0%) |
Diabetes | - | 4 (18.2%) | 4 (23.5%) | 5 (50.0%) |
Cardiovascular disease | - | 4 (18.2%) | 3 (17.6%) | 1 (10.0%) |
Echocardiographic data | ||||
TAPSE (mm) | 23.8 |
20.2 |
19.8 |
16.8 |
PAD (mm) | 20.2 |
23.8 |
23.6 |
25.4 |
TRPG (mmHg) | - | 25.5 |
27.2 |
30.8 |
PASP (mmHg) | - | 29.6 |
32.5 |
36.6 |
IVCmax (mm) | 14.4 |
13.9 |
15.2 |
17.3 |
IVCmin (mm) | 7.7 |
6.0 |
8.7 |
10.6 |
ICV-CI (%) | 50.4 |
57.1 |
44.4 |
42.3 |
LVEDD (mm) | 43.6 |
45.2 |
45.4 |
44.9 |
RVD (mm) | 17.6 |
34.5 |
34.4 |
34.7 |
RAD (mm) | 30.4 |
32.6 |
32.8 |
34.7 |
LVEF (%) | 64.8 |
64.9 |
61.5 |
59.6 |
AV (cm/s) | 117.4 |
113.3 |
110.4 |
114.7 |
Note: ARDS: acute respiratory distress syndrome; HR: heart rate;
MAP: mean arterial pressure; APACHE II: Acute Physiology and Chronic Health
Evaluation II; PAD: pulmonary artery diameter; TRPG: tricuspid valve
regurgitation pressure gradientbiggest; PASP: pulmonary arterial systolic
pressure; TAPSE: tricuspid annular plane systolic excursion; IVCmax: maximum
diameter of the inferior vena cava; IVCmin: minimum diameter of the inferior vena
cava; ICV-CI: inferior vena cava collapse index; LVEDD: left ventricular
end-diastolic dimension; RVD: right ventricular diameter; RAD: right atrial
diameter; LVEF: left ventricular ejection fraction; AV: aortic valve velocity.
|
Our results demonstrated that RV dysfunction is an important clinical feature in COVID-19 pneumonia patients with ARDS, which is related to the severity of COVID-19 pneumonia and ARDS. Bedside echocardiography allows for an early integrated assessment of the RV function through the evaluation of TAPSE. The echocardiographic parameters of RV function and cardiac cavity in COVID-19 pneumonia patients show abnormity to different extents compared to healthy subjects.
Viral pneumonia is the one of the most common causes for ARDS and is associated with high morbidity and mortality worldwide, such as in SARS, and H1N1 (Brown et al., 2011; S. Li et al., 2020; Viasus et al., 2011). RV dysfunction is frequently presented in these patients, and contributes to left-right asymmetry of the heart, which can worsen hemodynamic stability and is associated with a poorer prognosis (Arrigo et al., 2019; Biswas, 2015; Repesse et al., 2016). In our study, a higher incidence of RV dysfunction was found in critically-severe group of COVID-19 pneumonia who had more severe ARDS, which is a finding similar to that in the severe ARDS population caused by SARS and H1N1 viruses (Shorr et al., 2017; Viasus et al., 2011; Yin and Wunderink, 2018). Thus, RV dysfunction is common in viral pneumonia patients, especially in patients with severe ARDS.
TAPSE is the most commonly used index for evaluating RV function. This index has
been used in patients with ARDS and other clinical conditions, e.g. in patients
with cardiac surgery (Wranne et al., 1991), pulmonary embolism (Deng and Peng, 2010), and RV myocardial infarction (Alam et al., 2000). A TAPSE less
than 17 mm was recommended as a major parameter of RV dysfunction by ASE
guidelines. In present study, we found the TAPSE in patients with COVID-19
pneumonia was significantly decreased compared to healthy people, and the
proportion of patients with TAPSE
The function of the RV is to keep proper pulmonary perfusion pressure and systemic venous pressure to maintain normal blood flow (Zochios and Jones, 2014). The main factors affecting the RV function in patients with ARDS include impaired RV contraction and increased pulmonary vascular resistance. Previous research has indicated that an increase of pulmonary vascular resistance may be induced by higher PEEP, vasoconstrictor, hypoxemia, hypercapnia, and acidosis, which can deteriorate right heart structure and function (Price et al., 2010, 2012). In our study, we found that decreased TAPSE was associated with higher PEEP. Recent studies have shown that the clinical characteristics of severe and critically-severe COVID-19 pneumonia patients include severe hypoxemia, hypercapnia and microthrombosis, which may lead to higher pulmonary vascular resistance (Lazzeri et al., 2020; D. Wang et al., 2020; Wu and McGoogan, 2020; Yang et al., 2020).
In our study, the values of TRPG and PASP were higher than normal ranges and increased in COVID-19 pneumonia patients. Although the majority of patients in the critically-severe group received mechanical ventilation, there were no significant differences in TRPG and PASP between severe and critically-severe patients. This finding might be explained by the fact that pulmonary vascular resistance does not significantly increase by positive pressure mechanical ventilation and is not seriously deteriorated in the early stages of the disease (Paternot et al., 2016). The right heart had a poor ability to regulate pressure load (Mekontso Dessap et al., 2016). In this study, the right heart cavity and pulmonary artery were enlarged soon after the increase of pulmonary vascular resistance in patients with COVID-19 pneumonia.
Patients with critically-severe COVID-19 pneumonia are often accompanied by organ dysfunction and shock. The results of the present study have shown that both RV and left ventricular systolic function in critically-severe patients with COVID-19 pneumonia are impaired. The hemodynamic instability of decreased LVEF and MAP is associated with more severe RV dysfunction, which present significantly decreased TAPSE, enhanced diameters of IVC and reduced ICV-CI. Therefore, the monitoring and protection of right ventricular function need to be strengthened in the management of patients with COVID-19 pneumonia.
There are limitations in the present study. This is a retrospective study with limited sample size. Unfortunately, the representative TAPSE ultrasound images were not saved and some parameters were not routinely measured in all selected patients, such as RV fraction area change, cardiac output, left ventricular fraction shortening. The results need to be further confirmed by prospective clinical studies. ARDS often causes right heart dysfunction rather than left heart dysfunction. A recent study suggested that left ventricular systolic function is preserved in the majority of patients with COVID-19 infection, but RV function is impaired (Szekely et al., 2020). Thus, we paid more attention to the echocardiographic data of right heart. It is unknown whether RV dysfunction is worst in ARDS caused by the COVID-19 infection compared with other etiologies. Future studies may be required to investigate RV function in different medical conditions. In addition, although echocardiography was performed by ultrasonologist, it became more challenging than usual to obtain parameters since three-level isolation and protection measures must be taken when contacting patients with COVID-19 pneumonia. Although Speckle tracking echocardiography was reported as a novel echocardiographic technique to assess RV function, it is not routinely used in ARDS patients, especially for critically-ill patients (Bonizzoli et al., 2018). In this case, transthoracic echocardiography is the most important bedside examination method for evaluating patients with COVID-19 pneumonia.
RV dysfunction is relatively common in patients with severe and critically-severe COVID-19 pneumonia, which is related to the severity of illness. Early monitoring of RV function is very important for these patients. It is suggested that bedside echocardiography might be used as an objective test in the assessment of RV function in COVID-19 pneumonia patients with ARDS. TAPSE may serve as a quantitative indicator of early detection of RV dysfunction. These findings are helpful to further improve the clinical diagnosis and treatment strategies for patients with COVID-19 pneumonia.
ASE: American society of echocardiography; ARDS: Acute respiratory distress syndrome; AV: Aortic valve velocity; COVID-19: Coronavirus disease 2019; EDV: End-diastolic volume; ESV: End-systolic volume; HR: Heart rate; ICU: Intensive care unit; ICV-CI: Inferior vena cava collapse index; IVC: Inferior vena cava; IVCmax: Maximum diameter of the inferior vena cava; IVCmin: Minimum diameter of the inferior vena cava; LVEDD: Left ventricular end-diastolic dimension; LVEF: Left ventricular ejection fraction; MAP: Mean arterial pressure; PAD: Diameter of pulmonary artery; PASP: Pulmonary arterial systolic pressure; RAD: Right atrial diameter; RV: Right ventricular; RVD: Right ventricular diameter; RVOT: Right ventricular outflow tract; SARS-CoV-2: SARS coronavirus 2; SD: Standard deviation; TAPSE: Tricuspid annular plane systolic excursion; TRPG: Tricuspid valve regurgitation pressure gradient biggest.
Yunlong Li, Ming Li, Rong Tang collected the epidemiological and clinical data. Ming Ye, Hongliang Wang guided the study design. Yunlong Li, Junbo Zheng, Yu Jin, and Chunhong Xiu summarized all data. Yunlong Li, Junbo Zheng and Chunhong Xiu drafted the manuscript. Kaijing Yu, Ming Ye and Mingyan Zhao revised the final manuscript. All authors read and approved the final manuscript.
The study was approved by the ethics committee of the Second Affiliated Hospital of Harbin Medical University (KY2020-015).
We thank all patients and healthy volunteers involved in the study.
The authors declare no conflict of interest.