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Back to Journal »International Journal of General Medicine» Volume 14

Hemodynamic characteristics of myocardial injury and cardiogenic shock caused by severe COVID-19-related pneumonia

Author Liu Y, Chen Y, Chen J, Kuan Y, Tan N, Jiang K, Peng S, Hu C

Published on December 14, 2021, the 2021 volume: 14 pages 9647-9655

DOI https://doi.org/10.2147/IJGM.S334442

Single anonymous peer review

Editor approved for publication: Dr. Scott Fraser

Liu Yongjun,1,* Chen Yue'e,2,* Chen Jie,3 Yukung Kuang,4 Niandi Tan,5 Kejiang,6 Shuihui Peng,7 Chunlin Hu2 1Department of Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong Province, China People's Republic of China; 2Department of Emergency Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong; 3 Department of Critical Care Medicine, Dongguan People's Hospital, Dongguan, Guangdong Province, 523059; 4Department of Pulmonary Disease and Critical Care Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong 5 Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080; 6 Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022; 7 Department of Pharmacy, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080 This article has equal contributions. Corresponding author: Hu Chunlin, Department of Emergency, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080 Email [email protected] Peng Shuihui, Intravenous Admixture Service Department, Department of Pharmacy, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, Guangdong, People's Republic of China Email [email protected] Purpose: To observe the hemodynamic characteristics of a series of patients with myocardial injury caused by COVID-19-related pneumonia. Materials and methods: We successively collected clinical data of patients with severe COVID-19 pneumonia in the West District of Wuhan Union Hospital and Dongguan People's Hospital of Dongguan City to explore the prevalence and hemodynamic characteristics of myocardial injury after circulatory failure. Doppler ultrasound and PiCCO2 were used to evaluate the hemodynamics of each patient, and arterial blood gas analysis was performed at the same time. Pearson correlation analysis is used to clarify the relationship between parameters. Results: A total of 376 patients were observed during the study. 87 patients developed myocardial injury after admission. The average time of myocardial injury after admission was 6 (2, 30) days. Among them, 16 patients developed hemodynamic instability, and 15 died of cardiogenic shock or combined with MODS. Cardiac ultrasound revealed that all patients had LVEF within the normal range, and diastolic function was slightly to moderately impaired. PiCCO2 data showed that GEF was significantly reduced in all patients. dpmx is within the normal range. EVLWI, SVRI and GEDI are significantly increased in most patients. Pearson correlation analysis showed that cTNI was significantly correlated with BNP when hemodynamics was unstable (r=0.662, p=0.005); GEF was correlated with EVLWI (r = − 0.572, p = 0.021) and LAC (r = 0.692, p = 0.003) Correlation; EVLWI is affected by LVEF (r = − 0.564, p = 0.023), LVDF (r = − 0.734, p = 0.001) and PVPI (r = − 0.524, p = 0.037). Conclusion: Severe COVID-19-related pneumonia causes myocardial damage and cardiogenic shock. The hemodynamic status after cardiac shock is characterized by increased cardiac preload and EVLWI, accompanied by a decrease in GEF. Keywords: COVID-19, PiCCO2, myocardial injury, hemodynamic instability

Coronavirus disease 2019 (COVID-19) is a global pandemic. Although most patients will recover, patients with severe diseases, especially elderly patients, have a higher mortality rate. 1,2 COVID-19 is a systemic disease that damages various systems throughout the body. Elderly patients have many underlying diseases. Since the emergence of the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 combined with basic conditions has led to aggravation of the disease and increased mortality. SARS-CoV-2 infects host cells through the angiotensin-converting enzyme 2 (ACE2) receptor, leading to COVID-19-related pneumonia, as well as acute myocardial injury and chronic cardiovascular system damage. 3 Myocardial damage associated with SARS-CoV-2 cases occurred in 5 of the first 41 patients diagnosed with COVID-19 in Wuhan, China, mainly manifested by elevated levels of high-sensitivity cardiac troponin I (hs-TnI) ( >28 pg/mL). 4 In another report, among the 138 COVID-19 patients in Wuhan, 36 patients with severe symptoms were receiving treatment in the intensive care unit (ICU). 5 The levels of biomarkers of myocardial injury in patients receiving treatment in the ICU were significantly higher than those in the ICU of patients not receiving treatment in the intensive care unit, suggesting that patients with severe symptoms are often accompanied by complications such as acute myocardial injury. 4 However, the impact of myocardial injury on the hemodynamics of patients is still unclear.

Pulse-indicated continuous cardiac output (PiCCO) monitoring technology is a combination of pulse contour continuous cardiac output measurement and transpulmonary temperature dilution cardiac output measurement technology, which can systematically monitor the patient's hemodynamic status. 6,7 This study uses PiCCO to monitor the hemodynamic changes of a series of severe coronavirus disease-related pneumonia patients after myocardial injury, which will help doctors make treatment decisions.

All patients were confirmed to be infected with SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) and were sent to designated hospitals (West campus of Union Hospital of Huazhong University of Science and Technology in Wuhan, and ICU ward of Dongguan People's Hospital). We prospectively collected and analyzed data obtained from electronic medical records from February 8 to April 7, 2020, including clinical charts, nursing records, laboratory examination results, and chest X-rays.

If the serum level of the cardiac biomarker hs-TnI is >28 pg/ml4 or the ECG and echocardiogram show new abnormalities, the diagnosis is cardiac injury. COVID-19-related myocardial injury shows non-characteristic ECG changes, such as ST segment shift, pre-systole, atrioventricular block, or sinus tachycardia. All patients were screened for clinical chest pain symptoms and ECG changes to rule out acute myocardial infarction (AMI). AMI electrocardiogram is mainly characterized by ST-segment changes, with localization features, mainly ST-segment elevation, followed by T-wave peak and inversion, and finally a pathological Q wave. ST-segment changes are divided into ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI).

As previously reported, ejection fraction is measured by a quantitative 2-D method. 8 Diastolic function is assessed by pulse wave Doppler examination of mitral valve blood flow, pulmonary venous blood flow, and Doppler imaging of the medial mitral annulus. 8 Diastolic dysfunction is graded as 4-point ordinal number: 1) Normal; 2) Mild diastolic dysfunction = abnormal diastole, LV end-diastolic filling pressure does not increase (E/A ratio decrease <0.75); 3) Moderate or " Pseudo-diastolic dysfunction = abnormal diastole accompanied by increased LV end-diastolic filling pressure (E/A 0.75 to 1.5, deceleration time >140 ms, plus the other 2 Doppler indices for increased end-diastolic filling pressure); 4 ) Or severe diastolic dysfunction = advanced reduction in compliance, (ie, a significant increase in stiffness), restrictive filling (E/A ratio>1.5, deceleration time <140 milliseconds, and a much higher LV end-diastolic filling pressure Puller Index).

The patient is placed in a supine position. The right femoral artery was dissected and a 6F arterial catheter was inserted to measure blood pressure and cardiac output through the femoral artery thermodilution system (PiCCO2, Pulse Medical Systems, Munich, Germany). PiCCO2 is a pulse-indicating continuous cardiac output (PiCCO) technology that combines pulse contour analysis and thermodilution, which can comprehensively evaluate the patient's hemodynamic status. PiCCO2 can monitor the following indicators: 1. Cardiac output indicators, such as cardiac output (CO) and stroke volume (SV); 2. Blood volume indicators, such as total end diastolic volume (GEDV), intrathoracic blood volume (ITBV) ), stroke volume variability (SVV), pulse pressure variability (PPV), etc.; 3. Organ function indicators, such as extravascular lung water (EVLW) and pulmonary vascular permeability index (PVPI); 4. Vascular resistance indicators , Such as systemic peripheral vascular resistance (SVR) and arterial blood pressure (AP); 5. Heart function indicators, such as cardiac function index (CFI), global ejection fraction (GEF), left ventricular contraction index (dPmx), etc.

Use arterial pulse contour analysis and pulmonary thermodilution calibration to start continuous hemodynamic monitoring. At least 3 boluses of iced (<8 °C) 0.9% saline into the right internal jugular vein through a central venous catheter, and use a thermodilution curve to estimate hemodynamic variables. Perform three consecutive injections for calibration during setup, repeating every eight hours, or more frequently if special conditions change.

Continuous variables are expressed as the median (interquartile range [IQR]) and compared using the Mann-Whitney U test. Pearson correlation analysis is used to analyze the relationship between different variables. Use SPSS software version 13.0 (IBM Corporation, Armonk, NY, USA) for statistical analysis.

A total of 376 patients were observed during the study, and all patients met the diagnostic criteria for severe COVID-19. According to the seventh edition of the COVID-19 pneumonia diagnosis and treatment plan, patients with severe COVID-19 need to inhale oxygen to maintain SpO2>93% (Figure 1). Twenty-five patients with myocardial injury at the time of admission were excluded, and 3 patients with myocardial injury during hospitalization were determined by the research team as acute myocardial infarction and were also excluded. 87 patients had myocardial injury after admission. The average time of myocardial injury after admission was 6 (2, 30) days, and the average time of discharge was 21 (11, 60) days, of which 16 cases developed hemodynamic instability. Vasoactive drugs are required to maintain the average arterial pressure above 70 mmHg. Only 1 of these 16 patients survived and was discharged, and the remaining 15 died of cardiogenic shock or combined with MODS (Table 1). Three of the 15 patients who died received ECMO to support cardiopulmonary failure. Table 1 Basic information of patients Figure 1 Flow chart of patient recruitment.

Table 1 General information of patients

Myocardial injury continued to progress, and the levels of cTNI, Myo, CK-MB, and pro-BNP gradually increased, significantly higher than those at admission (Table 2). Table 2 Myocardial injury time and hemodynamic instability after admission

Table 2 Myocardial injury time and hemodynamic instability after admission

After hemodynamic instability, we used bedside echocardiography to assess the patient's cardiac function (Table 1). The LVEF of all patients was within the normal range, and the diastolic function was slightly to moderately impaired. All patients had a history of hypertension and mild ventricular septal hypertrophy (9-11 mm). Almost at the same time, we use PiCCO2 to monitor the patient's hemodynamics. PiCCO2 data are shown in Table 3, and the results of arterial blood analysis are shown in Table 4. The results showed that the GEF (reflecting the entire systolic function of the heart) of all patients was significantly reduced. Dpmx (reflecting left ventricular contractility) is close to the normal range, SVRI (reflecting cardiac afterload) is significantly increased, which may be related to the use of vasoactive drugs, and GEDI (reflecting volume load) is significantly increased in most cases. patience. The ELWI (reference value 3–7 mL/kg) of all patients increased significantly. Table 3 Parameters monitored by PiCCO when hemodynamics are unstable

Table 3 Parameters monitored by PiCCO when hemodynamics are unstable

Table 4 GEM Premier 3500's arterial blood gas analysis of patients when hemodynamics is unstable

Pearson correlation analysis is used to analyze the relationship between all variables. cTNI is significantly correlated with BNP when hemodynamics is unstable (r=0.662, p=0.005). GEF is related to ELWI (r=-0.572, p=0.021) and LAC (r=0.692, p=0.003). ELWI is affected by LVEF (r=-0.564, p=0.023), LVDF (r=-0.734, p=0.001) and PVPI (r=-0.524, p=0.037). For related analysis of other parameters, please refer to the supplementary materials.

In this study, we conducted continuous observations on 376 severely ill patients. 87 of the 376 patients (23.1%) developed myocardial injury after admission, 16 of the 87 patients (18.4%) developed circulatory failure and required the use of vasoactive drugs, and 3 patients received ECMO due to cardiopulmonary failure. At the same time, we also use bedside ultrasound and PiCCO2 to evaluate the patient's hemodynamics. We found that the EVLWI of the patient increased significantly.

ELWI is one of the indicators reflecting the severity of extravascular pulmonary hydrops in patients with severe sepsis, and is closely related to the prognosis of patients. The factors affecting EVLWI are pulmonary and cardiogenic. Early autopsy studies found that in patients with severe COVID-19-related pneumonia, alveolar capillary congestion, capillary leakage caused fibrin exudation and fibrin precipitation to form a hyaline membrane, accumulation of monocytes in the alveolar cavity, and accumulation of squamous epithelial metaplasia. 9 Pearson correlation analysis showed that ELWI was significantly correlated with LVEF (r=-0.564, p=0.023), LVDF (r=-0.734, p=0.001) and PVPI (r=-0.524, p=0.037)). Metaplastic alveolar epithelial cells may also be one of the sources of EVLWI, which is different from the phenomenon previously observed in patients with severe ARDS. 10-12 Whether EVLWI can predict the prognosis of patients with COVID-19-related pneumonia remains to be confirmed through further studies. The increase in ELWI is related to a decrease in left ventricular diastolic function or an increase in non-vascular water sources in the lungs. The increase of ELWI will inevitably affect the gas exchange in the lungs, leading to the occurrence of hypoxemia. Blood gas analysis showed that the difference between alveolar air and arterial oxygen partial pressure increased significantly, indicating that oxygen diffusion is obstructed.

Although the heart is not the main organ affected by COVID-19, the incidence of myocardial injury in severely ill patients with COVID-19-related pneumonia is still high, and the mortality rate of patients with myocardial injury has increased significantly. 13-15 Viral infection sepsis can also cause MODS, autopsy reports 9,16 myocardial edema, weight gain, and epicardial lymphocyte infiltration. The central CMC showed vacuolar degenerative changes without inflammatory cell infiltration. 9 Studies have shown that myocardial edema affects the efficiency of myocardial energy metabolism and impairs the systolic and diastolic functions of the heart. 17,18 Septic myocardial damage caused by bacterial infection also affects myocardial remodeling, 18,19 and whether myocardial damage caused by COVID-19 also leads to myocardial remodeling remains to be confirmed by future studies.

In this study, we observed that in most patients with impaired diastolic function, ventricular diastolic dysfunction can impair myocardial response to fluid load by increasing diastolic filling pressure and ventricular wall tension, while impairing microvascular flow and aggravating the myocardium damage. Left ventricular diastolic dysfunction can lead to an increase in pulmonary capillary hydrostatic pressure, which often leads to an increase in EVLWI. In addition, most patients suffer from diseases that may impair ventricular diastolic function, such as hypertension and coronary heart disease.

Therefore, the hemodynamics of COVID-19-related pneumonia is not exactly the same as that of sepsis, showing its particularity: (1) The permeability of pulmonary capillaries is not as good as that of sepsis. Pulmonary interstitial edema is not entirely water; it also includes changes in alveolar exudate tissue and pulmonary interstitial fibrosis, which has been confirmed by autopsy. (2) PiCCO2 monitoring showed that the patient's cardiac preload and ELWI increased, pulmonary artery spasm caused by hypoxia, increased pulmonary artery resistance, and right heart dysfunction were induced, which was consistent with the results of cardiac ultrasound. Therefore, the patient does not lose a large amount of effective circulating blood volume, so shock cannot be corrected by fluid replacement. On the contrary, it may cause an increase in pulmonary hydrostatic pressure and extravascular lung water, thereby further aggravating the symptoms of hypoxia. A recent study compared the difference between ARDS caused by COVID-19 and non-COVID-19; Shi et al. 20 studies found that the EVLWi and PVPI values ​​of patients with COVID-19 ARDS increased significantly after the onset The severe alveolar damage caused by COVID-19 is consistent and thus related to the results of this study. The difference is that the 16 patients in this study were seriously ill, and the GEF decreased significantly.

The current research has the following limitations. First, in this study, patients with myocardial injury were monitored by PiCCO after hemodynamic instability. Whether EVLWI increases after lung injury or when hemodynamic instability occurs after myocardial injury is uncertain. Secondly, PiCCO is a very useful hemodynamic monitoring method, usually used for hemodynamic monitoring of critically ill patients; for patients with severe COVID-19 related pneumonia, if there is no hemodynamic instability, it is not necessary to use PiCCO is monitored, so in non-critically ill patients, it is not clear whether they have elevated EVLWI. In future research, we should improve the method for accurately assessing right ventricular function in patients with COVID-19 ARDS. More clinical evidence is needed to confirm whether the impairment of right ventricular function and the increase in EVLWI can reflect the severity of ARDS in COVID-19 patients?

The myocardial damage caused by severe COVID-19-related pneumonia and the hemodynamic status after cardiogenic shock is characterized by increased cardiac preload and EVLWI, while GEF decreased.

The patient or the patient’s close relatives provided written informed consent to participate in this study. This data is anonymous or confidential. The publication of this study complies with the Declaration of Helsinki. According to the local legislation and institutional requirements of the National Health Commission of China and the Ethics Committee of Wuhan Union Medical College Hospital, observational research on human participants does not require ethical review and approval. The research is exempt from approval by the institutional review board.

My sincere thanks to the West Campus of Union Hospital of Huazhong University of Science and Technology, the First Affiliated Hospital of Sun Yat-Sen University and all patients who participated in this study. This research was funded by the Shenzhen Science and Technology Research and Development Fund (JCYJ20160608142215491) and the Guangdong Basic and Applied Basic Research Fund (2020A1515010120 and 2020A1515110919). Funders have no role in research design, data collection, analysis, publication decisions, or manuscript preparation.

The authors declare that they have no conflicts of interest.

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