key: cord-0993283-1f2lxr6q
authors: Kahyaoglu, Muzaffer; Guney, MuratCan; Deniz, Derya; Kilic, Ertugrul
title: Right ventricle early inflow‐outflow index may inform about the severity of pneumonia in patients with COVID‐19
date: 2021-10-28
journal: J Clin Ultrasound
DOI: 10.1002/jcu.23066
sha: c3711dc9a88775441075c0f5f4890c23278d9fc8
doc_id: 993283
cord_uid: 1f2lxr6q

BACKGROUND: Echocardiography is generally used in our daily practice to detect cardiovascular complications in COVID‐19 patients and for etiological research in the case of worsened clinical status. Many echocardiographic parameters have been the subject of investigation in previous studies on COVID‐19. Recently, the right ventricle early inflow‐outflow (RVEIO) index has been identified as a possible and indirect marker of the severity of tricuspid regurgitation and right ventricular dysfunction in pulmonary embolism. In this study, we aimed to investigate the relationship between the severity of pneumonia in COVID‐19 patients and the RVEIO index. METHODS: A total of 54 patients diagnosed with COVID‐19 pneumonia were enrolled in this study. Our study population was separated into two groups as severe pneumonia and nonsevere pneumonia based on computed tomography imaging. RESULTS: Saturation O(2), C‐reactive protein, D‐dimer, deceleration time, tricuspid annular plane systolic excursion, tricuspid lateral annular systolic velocity, and RVEIO index values were found to be significantly different between severe and nonsevere pneumonia groups. The result of the multivariate logistic regression test revealed that saturation O2, D‐dimer, Sm, and RVEIO index were the independent predictive parameters for severe pneumonia. Receiver operating characteristic curve analysis demonstrated that RVEIO index >4.2 predicted severe pneumonia with 77% sensitivity and 79% specificity. CONCLUSION: The RVEIO index can be used as a bedside, noninvasive, easily accessible, and useful marker to identify the COVID‐19 patient group with widespread pneumonia and, therefore high risk of complications, morbidity, and mortality.

COVID-19 disease continues to affect the whole world as a pandemic health crisis characterized by a wide spectrum of clinical manifestations varying from asymptomatic infection to multi-organ dysfunction. 1 Although initially it has been thought to be a disease presenting with viral pneumonia, it may also occur with clinical manifestations affecting multiple organ systems. 1 The cardiovascular system is one of the most frequently affected systems, and there is an increasing prevalence of cardiovascular complications, including new or worsening heart failure, arrhythmia, acute myocarditis, and myocardial infarction, particularly in severely and critically ill patients. 2, 3 However, in some patients, cardiac test abnormalities can be the only finding with the absence of the clinical signs of heart disease. 4 The cardiovascular system can be affected by COVID-19 due to the direct damage to cardiomyocytes, or it may be affected due to the heart-lung interaction. 2, 3 The right ventricle (RV) is often indirectly involved during the course of COVID-19 disease. 5 Right cardiac functions may be affected as a result of various pathophysiological mechanisms such as lung parenchymal damage, altered pulmonary hemodynamics, pulmonary vasoconstriction secondary to hypoxia, and thrombotic process. 6 Echocardiography is generally used in our daily practice to detect cardiovascular complications in COVID-19 patients and for etiological research in the case of worsened clinical status. 7 In previous studies, many echocardiographic parameters, including tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), pulmonary artery systolic pressure and RV strain have been associated with poor outcomes and mortality. 7 It has been observed that these parameters further deteriorated as the severity of the disease increased. Recently, the RV early inflow-outflow (RVEIO) index has been identified as a possible and indirect marker of the severity of tricuspid regurgitation and RV dysfunction in pulmonary embolism. 8, 9 Previous studies have emphasized that ultrasonographic examinations, especially lung ultrasound (LUS), can provide information about the lung involvement and the severity of pneumonia in COVID-19 patients. 10, 11 However, no study was found in the literature investigating the relationship between echocardiographic parameters and the severity of pneumonia. Based on this information, in this study we aimed to investigate the relationship between the severity of pneumonia in COVID-19 patients and the newly defined RVEIO index as an indirect indicator of RV dysfunction based on the heart-lung interaction.

A total of 54 patients diagnosed with COVID-19 pneumonia between November 2020 and January 2021 were prospectively enrolled in this study. The patients were consecutively enrolled in the study. According to the interim guidance of the World Health Organization, COVID-19 diagnosis was established via reverse transcriptase-polymerase chain reaction test of the nasopharyngeal swab. Patients having pneumonia from COVID-19 diagnosed with chest computed tomography (CT) imaging were examined. Patients with known pulmonary hypertension, chronic lung pathologies, previous or current pulmonary embolism, severe renal failure, severe valvular disease, heart failure, atrial fibrillation, or poor echocardiographic images were excluded from the study. This study was approved by the local ethics committee (Decision number: 2020/20/03) and the our ministry of health.

Patients' demographics, clinical characteristics, and laboratory findings were collected from our hospital's medical records. All blood samples were obtained from the patients at the time of admission.

The severity of pneumonia was studied in the previous research, and three categories were described as mild, moderate, and severe according to the CT findings. 12, 13 In mild pneumonia, the pulmonary parenchyma was normal or near normal. In moderate pneumonia, ground-glass opacities, typically with a peripheral and subpleural distribution, were the main CT findings. In the presence of severe pneumonia, consolidation, linear opacities, and crazy-paving patterns were demonstrated. 12, 13 Our study population was separated into two groups as severe pneumonia and nonsevere pneumonia (mild and moderate) based on CT imaging.

Echocardiographic assessment was performed in all patients at the time of intensive care unit admission by the same echocardiographer who was blinded to the study design and patients' clinical data, using a commercially available system (Affiniti 50; Philips Healthcare, Andover, Massachusetts, USA) equipped with a 2.5-4 MHz transducer.

Echocardiography was performed before starting mechanical ventilation in order to avoid impairment of the right ventricular filling hemo- (RVOT) on the parasternal short-axis view. RVEIO index was obtained using the following equation: RVEIO index = Early trans-tricuspid filling wave velocity (E-wave velocity [cm/s]∕RVOT VTI) ( Figure 1 ). Other clinical and demographic characteristics and laboratory findings were similar between the two groups.

The echocardiographic parameters of the nonsevere and severe pneumonia groups are presented in 1.304-5.785; p = .008) were the independent predictive parameters for severe pneumonia (Table 3) .

Our results provide information about the severity of pneumonia in patients hospitalized in the intensive care unit for COVID-19 and the principal findings of our study are as follows: (i) RVEIO index values were higher in the severe group compared to the nonsevere group;

(ii) saturation O2, D-dimer levels, Sm, and RVEIO index were found to be independent predictors of severe pneumonia through multivariate analysis.

COVID-19 affects the heart both directly or indirectly in as much as half of patients, and cardiovascular involvement is associated with a poor prognosis. 2, 3 In the clinical course of COVID-19, myocardial injury, myocarditis, myocardial infarction, stress cardiomyopathy, and arrhythmias could be observed. 2, 3 And also, COVID-19 causes disturbances in heart functions, especially as a result of the heart-lung interaction. 2, 3 The RV appears to be one of the most affected cardiac chambers. 16 Direct myocardial damage, increased vasoactive mediators, vascular remodeling, vascular thrombosis, and vascular compression secondary to atelectasis and edema contribute to RV dysfunction. 17 In previous studies, many RV parameters have been reported as predictors of in-hospital and short-term mortality and morbidity in patients with COVID-19. 7 Obvious and subtle changes in the RV are often detected with echocardiography. 7 In COVID-19

patients, echocardiography has become a useful clinical tool both in medical wards and in critical care settings since it can provide information on concomitant clinical conditions (i.e., heart failure, myocardial infarction), current hemodynamic status, and the heart-lung interactions. 2, 3 In previous studies, it has been determined that the right heart functions are significantly impaired especially in the critically severe disease group in COVID-19 patients, and are related to the prognosis. 18, 19 Previous studies have emphasized that RV dysfunction is related to the severity of COVID-19 pneumonia and acute respiratory distress syndrome. 18, 19 These studies have mostly focused on parameters such as TAPSE, Sm, FAC, and RV speckle tracking parameters, which show RV dysfunction. 7, 18, 19 In this study, we emphasized that RVEIO index studied in determining the severity of tricuspid regurgitation and evaluating right ventricular dysfunction in pulmonary embolism may be related to the severity of COVID-19 pneumonia, and as a result of our study, we determined it as an independent predictive parameter for severe pneumonia. Regarding the mechanism, association between RVEIO index and severe pneumonia, that has been observed in our study, may stem from compensatory adaptation to increased RV afterload and pulmonary vascular resistance (PVR).

The main factor in right ventricular failure in COVID-19 pneumonia is considered to be an increase in PVR. 18 As the severity of pneumonia increases, it will create a more serious burden on the RV with factors such as lung edema, thickening of alveolar septa, inflammatory F I G U R E 2 Receiver operating characteristic curve analysis of the right ventricle early inflow-outflow (RVEIO) index to predict the severe pneumonia (AUC: Area under the curve) showing the severity of pneumonia could identify patients who needed aggressive treatment and close monitoring. 23, 24 In this study, we showed that the RVEIO index is a surrogate marker for severe pneumonia, a disease with possibly high mortality and morbidity, requiring close follow-up.

Ultrasonography is used with increasing frequency in our daily practice. Point-of-Care Ultrasound emerges as a powerful tool that is frequently used in patient approach in the emergency room or intensive care unit. Previous studies showed that LUS has been often used for disease identification, lung involvement severity classification, or treatment allocation in the emergency department during the COVID-19 pandemic. 22, 25 It has also been shown that LUS can reduce the use of chest X-rays and CT. 26 Echocardiography is usually used in emergency services or intensive care units for hemodynamic disorders, detection of complications, and cardiovascular evaluation. 5, 7 In addition to detecting cardiac involvement, echocardiography may speed up the identification of high-risk patients during the COVID-19 pandemic. It should be kept in mind that bedside echocardiography can also be used in this area. As a result of our study, the RVEIO index as an echocardiographic parameter may provide information about the degree of COVID-19 lung involvement.

There are several limitations in the present study. It was a singlecenter study with a relatively limited number of patients. Our findings must be supported by further large prospective studies. Since only COVID-19 patients admitted to the intensive care unit were included, our findings may not apply to the entire COVID-19 population. The intra-observer correlation was not analyzed in our study. In addition, TTE examinations were performed by a single researcher; thus, the inter-observer correlation could not be analyzed. RVEIO index and the other echocardiographic measurements have the disadvantage of being relatively angle-dependent. And the RVEIO index is, however, like all echocardiographic methods, dependent on image quality. Furthermore, intensive care unit patients may be unable to cooperate in adjusting positions, which affect image quality.

RVEIO index can be used as a bedside, noninvasive, easily accessible, and useful marker to identify the COVID-19 patient group with widespread pneumonia and therefore the high risk of complications, morbidity, and mortality.

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No potential conflict of interest was reported by the authors.

Research data are not shared.

https://orcid.org/0000-0002-8572-1725