COVID-19-associated myocardial injury
Main article: COVID-19
For COVID-19 frequently asked inpatient questions, click here
For COVID-19 frequently asked outpatient questions, click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed rizvi, M.B.B.S[[2]]
Synonyms and Keywords: Novel coronavirus, COVID-19, Wuhan coronavirus, coronavirus disease-19, coronavirus disease 2019, SARS-CoV-2, COVID-19, COVID-19, 2019-nCoV, 2019 novel coronavirus, cardiovascular finding in COVID-19, myocardial injury in COVID-19, COVID-19-associated myocardial injury, SARS-CoV2-associated myocardial injury, COVID-19 myocardial injury.
Overview
Coronavirus disease 2019 (COVID-19) is a rapidly expanding global pandemic which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Myocardial injury presented by high level of cardiac troponin is a common manifestation in COVID-19. The exact pathogenesis of myocardial injury is not clear yet. However, systemic inflammation, hypoxemia, vasopressor requirement, thrombophilia have been proposed as the underlying mechanisms of myocardial injury. Factors associated with myocardial injury including age creatinine, multisystem organ failure]] were similar in both COVID-19 and non COVID-19 patients. Myocardial injury was associated with poor outcome in critically ill COVID-19 patients. Myocardial injury in COVID-19 can be the manifestation of underlying critically illness and multisystem organ dysfunction, especially concomitant renal dysfunction, as well as thrombotic complications.
Historical Perspective
- COVID-19 (SARS-CoV-2) outbreak initiated and was discovered in December, 2019 in Wuhan, Hubei Province, China.[1]
- January 30, 2020 - World Health Organization(WHO) declared the outbreak as a Public Health Emergency of International Concern.[2]
- March 12, 2020 - WHO declared the COVID-19 outbreak a pandemic.[3]
- January 2, 2020 - first observational study of 41 patients with COVID-19 pneumonia showed that 5 (12%) of the 41 patients had elevated hs-TnI ( high sensitivity troponin) level above the defined threshold (28 pg/ml) [4]
- To view the full historical perspective of COVID-19, click here.
Classification
Following careful clinical evaluation, patients with cTn increases indicative of myocardial injury, including those with COVID-19, should be classified as [5]
- Chronic myocardial injury
- Acute non-ischemic myocardial injury
- Acute myocardial infarction (MI).
Chronic myocardial injury:[6]
- Chronic myocardial injury, a term that applies to patients with chronic stable (<20% change) cTn increases, can be frequently encountered in patients with COVID-19 as the patients are of older age and they have high prevalence of chronic cardiovascular disease.
Acute non-ischemic myocardial injury:[7]
- Acute non-ischemic myocardial injury, a term that applies to patients with dynamic rising and/or falling cTn concentration without clinical evidence of myocardial ischemia, is probably the predominant mechanism for cTn increases in patients with COVID-19.
Acute myocardial infarction (MI): [8]
- Symptoms of acute myocardial ischemia;
- New ischemic electrocardiographic (ECG) changes;
- Development of pathological Q waves;
- Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology;
- Identification of a coronary thrombus by angiography including intracoronary imaging or by autopsy
- To view the classification of COVID-19, click here.
Pathophysiology
The pathophysiology of COVID-19 acute myocardial injury depends on the underlying cause of myocardial tissue death. However, the overall trigger is an exaggerated inflammatory response (hyperinflammation) in response to viral infiltration into cells. SARS-CoV-2 virus gains entry via the ACE-2 (Angiotensin Converting Enzyme 2) receptor that is found abundantly in myocardial tissue and endothelium of blood vessels.
Proposed pathophysiological mechanisms of COVID-19 associated myocardial injury:
- SARS-CoV-2 downregulates ACE-2 expression and subsequent protective signaling pathways in cardiac myocytes
- Hyperinflammation and cytokine storm mediated through pathologic T-cells and monocytes leading to myocarditis[9]
- Respiratory failure and hypoxemia resulting in damage to cardiac myocytes[10]
- Hypercoagulability and development of coronary microvascular thrombosis[11]
- Diffuse endothelial injury and ‘endothelitis’ from direct cell invasion of SARS-CoV-2 and/or resulting from host inflammatory response.[12]
- Inflammation and/or stress causing coronary plaque rupture or supply-demand mismatch leading to myocardial ischemia/infarction.[13]
- Direct invasion of the cardiac tissue by COVID-19.[14]
Hyperinflammation and cytokine storm:
- Immune dysregulation, including T cell and immune signaling dysfunction, recognized as an important factor in the pathogenesis of vascular disease, may also adversely affect the body's response to SARS-CoV-2 infection[15]
- CD4(+) CD25(+) FOXP3(+) regulatory T (TREG) cells have played a role in inflammation. TREG cells { T regulatory cells}) plays a vital role in the induction and maintenance of immune homeostasis and tolerance, any dysregulation in the function or regenaration of TREG cells{ Regulatory T cells}) can trigger abnormal immune responses, that can lead to pathology.
- Naive T lymphocytes can be primed for viral antigens via antigen-presenting cells.[16]
- The primed CD8+ T lymphocytes migrate to the cardiomyocytes and through cell-mediated cytotoxicity, cause myocardial inflammation and cardio-tropism by heart-produced Hepatocyte Growth Factor (HGF) which interacts with c-Met, an HGF receptor on naïve T lymphocytes.[17]
- In the cytokine storm syndrome, proinflammatory cytokines such as Interleukin-6 (IL-6) are released into the circulation, which further augments T-lymphocyte activation and causes the release of more cytokines.[18]
- Cytokine storms result in increased vascular wall permeabilityand myocardial edema.[19]
- A positive feedback loop of immune activation and myocardial damage is established.
- Thus cytokine storm activated by T helper cells (Th1 and Th2) and a systemic hyperinflammatory response is triggered.[20]
Role of ACE-2 Receptor :
- ACE-2 is a membrane-bound aminopeptidate receptor expressed on the epithelial cells of the lungs, intestines, kidneys and blood vessels. It has important immune and cardiovascular roles. Angiotensin-converting enzyme (ACE) cleaves angiotensin I to generate angiotensin II (Ang II), which binds to and activates AT1R, thus promoting vasoconstriction.[21]
- ACE-2 cleaves angiotensin II and generates angiotensin 1–7, a powerful vasodilator acting through Mas receptors
- SARS-CoV-2 has a spike protein receptor-binding domain, similar to SARS-CoV, which interacts with the ACE-2 receptor and acts as the primary functional receptor for pathogenicity and human-to-human transmission. Furthermore, SARS-CoV-2 binding to ACE-2 leads to its down regulation and increases angiotensin II,a pro-inflammatory factor in the lung.[22] [23]
- This subsequently leads to lower amount of angiotensin 1–7. Thus loss of protective signaling pathway in cardiac myocytes. The detrimental effect of ACE-2 downregulation would impede cardioprotective effects of angiotensin 1–7 leading to increased TNFα production, other cytokines release that can result in acute respiratory distress syndrome, acute cardiac injury and multiorgan dysfunction.[24]
- To view the pathophysiology of COVID-19, click here
Causes
- Common causes of high troponin level in COVID-19 are:[25]
- Thrombotic , plaque rupture events
- Supply-demand mismatch
- Direct cardiac viral toxicity
- Older age
- Acute renal dysfunction
- Chronic renal dysfunction
- High serum lactate level
- Inflammation, prothrombothic state in COVID-19
- High level of ferritin as a marker of inflammation
- Low level of fibrinogen as a marker of consumption]], microvascular thrombi, endothelial dysfunction[26]
- Hypoxemia induced by Acute respiratory distress syndrome (ARDS)[27]
- Hypercoagulability and plaque rupture[28]
- Hyperinflammation and cytokine storm[29]
- Direct invasion of the cardiac tissue by SARS-CoV-2[30]
- To view causes of COVID-19, click here.
Differentiating COVID-19 associated Acute myocardial injury from other Diseases
- COVID-19 associated acute myocardial injury must be differentiated from other causes of myocardial injury not related to COVID-19 infection.
- The signs and symptoms of acute coronary syndrome, acute heart failure and myocarditis induced by COVID-19 cannot be differentiated from non-COVID-19 acute cardiac disease. Laboratory evaluation with hs-TnI, CK and LDH as well as EKG changes are similar and cannot differentiate between the two disease states
- All patients with COVID-19 induced myocardial injury must be PCR positive for SARS-CoV-2
- The majority of patients have other features of COVID-19, primarily fever, pneumonia and/or ARDS at initial presentation [31]
- A small number of patients have been reported to present primarily with COVID-19 associated myocardial injury and minimal to no other pulmonary/systemic symptom
- For chest pain differential diagnosis Click here
- For ACS differential diagnosis Click here
- For heart failure differential diagnosis Click here
- For myocarditis differential diagnosis Click here
- For the differential diagnosis of COVID-19, click here.
| COVID-19 associated AMI vs non COVID-19 AMI | ||
| Causes | Similar features | Features specific to COVID-19 |
| Acute coronary syndrome
- Type I & II MI |
Chest pain
Shortness of breath Elevated troponin I level Evidence of coronary occlusion by imaging/PCI |
Clinical evidence of SARS-CoV2 infection[33]
- Fever - Cough - Dyspnea - Bilateral ground glass opacities on chest imaging (Patients may have nonspecific symptoms such as fatigue and malaise without specific symptoms of cardiac disease) |
| Acute Heart failure[34] | Chest pain/pressure
Shortness of breath Elevated BNP Depressed ventricular function on echocardiography | |
| Myocarditis[35] | Chest pain
Fatigue S3,S4 or summation gallop Elevated troponin I EKG abnormalities Absence of coronary occlusion | |
| AMI- acute myocardial injury; BNP – Brain Natriuretic peptide; MI – myocardial infarction; NSTEMI - non ST Elevation Myocardial Infarction; PCI – percutaneous intervention; STEMI - ST elevation Myocardial Infarction | ||
Epidemiology and Demographics
| Study | Site/
Location |
Sample size (n) | Age (years) | Pre-existing cardiac disease | Definition of myocardial injury used in study | Percent with myocardial injury |
| Huang et al [36] | Wuhan, China | 41 | Median 49.0 | 15% cardiovascular disease
15% hypertension |
Cardiac injury=troponin I above 99th percentile upper reference limit or new abnormalities on electrocardiography or echocardiography | 12 |
| Shi et al[37] | Wuhan, China | 416 | Median 64.0 (range 21.0–95.0) | 4% chronic heart failure
11% coronary heart disease 31% hypertension |
Cardiac injury=troponin I above 99th percentile upper reference limit, regardless of new abnormalities on electrocardiography or echocardiography | 19.7 |
| Zhou et al [38] | Wuhan, China | 191 | Median 56.0 | 8% coronary heart disease
30% hypertension |
Cardiac injury=high-sensitivity troponin I above 99th percentile upper reference limit or new abnormalities on electrocardiography or echocardiography | 17 |
| Guo et al[39] | Wuhan, China | 187 | Mean 58.5±14.7 | 4% cardiomyopathy
11% coronary heart disease 33% hypertension |
Myocardial injury=troponin T above 99th percentile upper reference limit | 27.8 |
| Wang et al [40] | Wuhan, China | 138 | Median 56.0 | 15% cardiovascular disease
31% hypertension |
Cardiac injury=troponin I above 99th percentile upper reference limit or new abnormalities on electrocardiography or echocardiography | 7.2 |
Incidence
- The incidence of COVID-19 associated myocardial injury has not been established yet.
Prevalence
- The prevalence of myocardial injury (as reflected by elevation in cardiac troponin levels) is variable among hospitalized patients with COVID-19 and is known to be approximately 5,000-38,000 per 100,000 hospitalized individuals worldwide.[41]
- Reported frequencies range from 5% to 38%[42] [43] [44]
- In a series of 416 patients with COVID-19 who were hospitalized in Wuhan, China, 19.7 percent had high-sensitivity troponin I (hs-TnI) above the 99th percentile upper reference limit on admission.[45]
Case-fatality rate/Mortality rate
- A summary of 44,672 COVID-19 cases documented by the Chinese Center for Disease Control and Prevention demonstrated a case fatality rate of 10.5% with comorbid CVD (cardiovascular disease) compared to a 2.4% overall case fatality rate[46]
- The mortality rate was also higher in those with myocardial injury (51.2% versus 4.5%).[46]
Age
- Patients with this marker of myocardial injury were older and had more comorbidities (including chronic heart failure in 14.6% versus 1.5%), greater laboratory abnormalities (including higher levels of C-reactive protein, procalcitonin, and aspartate aminotransferase), more lung radiographic abnormalities, and more complications compared with those without myocardial injury.
Race
- As of June 12, 2020, age-adjusted hospitalization rates are highest among non-Hispanic American Indian or Alaska Native and non-Hispanic black persons, followed by Hispanic or Latino persons. CDC
- Non-Hispanic American Indian or Alaska Native persons have a rate approximately 5 times that of non-Hispanic white persons,
- Non-Hispanic black persons have a rate approximately 5 times that of non-Hispanic white persons,
- Hispanic or Latino persons have a rate approximately 4 times that of non-Hispanic white persons
Gender
- There is no data on gender predilection to acute myocardial injury in COVID-19.
Region
- COVID-19 is a pandemic.
Risk Factors
- A meta-analysis of 6 studies of 1,527 total patients with COVID-19 examined the prevalence of cardiovascular disease (CVD) and reported the prevalence of hypertension, cardiac and cerebrovascular disease, and diabetes to be 17.1%, 16.4%, and 9.7%, respectively [47]
- To view the risk factors of COVID-19, click here.
Screening
- There is insufficient evidence to recommend routine screening for acute myocardial injury in COVID-19 patients.
- To view screening for COVID-19, click here.
Natural History, Complications, and Prognosis
- Myocardial injury in severe COVID-19 was associated with underlying comorbidities, older age, multisystem organ dysfunction similar to non COVID-19 critically ill patients.[25]
Complications
- The disease also contributes to cardiovascular complications including [48]
Prognosis
- Prognosis of COVID-19 myocardial injury patients is generally poor and was associated with multisystem organ involvement and critical illness.[25][49]
- A retrospective analysis of the cause of death in Chinese patients infected with COVID-19 revealed that 40% of patients died at least in part because of myocardial injury and circulatory collapse.[50]
- In another study, patients hospitalized for COVID-19 infection developed cardiac injury in roughly 20% of cases; thus leading to greater than 50% mortality.[51]
- Older patients with preexisting cardiovascular comorbidities and diabetes are prone to develop a higher acuity of illness after contracting SARS-CoV-2 associated with higher risk of myocardial injury and a markedly higher short-term mortality rate.[52]
Diagnosis
| Initial Evaluation of Suspected Acute Myocardial Injury in COVID-19 |
| History [53] |
|
| Physical exam |
|
| EKG changes |
| Laboratory evaluation |
|
| Imaging studies |
| [53] |
For chest pain diagnostics click here
History and Symptoms
- Patients with COVID-19 present with the typical symptoms and signs of SARS-CoV-2 infection such as fever, cough, dyspnea. Acute myocardial injury in COVID-19 presents similar to non COVID-19 related ACS and heart failure. [55] [56]
- For ACS sign and symptoms please Click here
- For Heart failure sign and symptoms please Click here
- To view the history and symptoms of COVID-19, click here.
Physical Examination
- To view the complete physical examination in COVID-19, click here.
- To view physical exam of ACS Click here
- To view physical exam of Heart failure Click here
Laboratory Findings
- Cardiac Biomarkers:
- The upper reference limit for the high-sensitivity troponin I (hs-TnI) test (0.04ng/mL), is based on the 99th percentile of measurements reported in healthy population without the occlusion of coronary arteries.[57][58]
- In the recently published retrospective study of 191 COVID-19 patients from two separate hospitals in China, the incidence of elevation in high-sensitivity cardiac troponin I (cTnI) (>28 pg/ml) was 17%, and it was significantly higher among non-survivors (46% versus 1%, p<0.001).
- Furthermore, elevation of this biomarker was noted to be a predictor of in-hospital death (univariable OR 80.07, 95% CI [10.34–620.36], p<0.0001). The most abrupt increase in cTnI in non-survivors was noted beyond day 16 after the onset of disease. In the same study, the incidence of acute cardiac injury was 17% among all-comers, but significantly higher among non-survivors (59% versus 1%, p<0.0001).[59]
- CK-MB >2.2 ng/mL
- Guo et al11 provide additional novel insights that TnT levels are significantly associated with levels of C-reactive protein and N-terminal pro-B-type natriuretic peptide (NT-proBNP), thus linking myocardial injury to severity of inflammation and ventricular dysfunction[60]
Inflammatory biomarkers:
- Elevated levels of inflammatory markers including erythrocyte sedimentation rate, C reactive protein, and procalcitonin are usually seen in myocarditis but they are non-specific and do not confirm the diagnosis. Increases levels of Interleukin-6 (IL-6), d-dimer, serum ferritin, prothrombin time were seen in COVID-19 patients.
- To view the laboratory findings on COVID-19, click here.
Electrocardiogram
- The electrocardiogram (ECG) can demonstrate a range of findings[61]
- In some cases mimicking acute coronary syndrome (ACS).
- The ECG abnormalities result from myocardial inflammation and include non-specific ST segment-T wave abnormalities.
- T wave inversion.
- PR segment and ST segment deviations (depression and elevation)
- An ECG can help to find previous cardiac abnormalities and triggering factors, such as acute myocardial infarction, and arrhythmias.
- To view the electrocardiogram findings of ACS Click here
- To view the electrocardiogram findings heart failure Click here
- To view the electrocardiogram findings on COVID-19, click here.
X-ray
- There are no specific X-ray findings in COVID-19 associated myocardial injury.
- To view the x-ray findings on COVID-19, click here.
Ultrasound/Echocardiography
- There are no specific ultrasound/ echocardiographic findings related to COVID-19-associated acute myocardial injury
- To view the echocardiographic findings on COVID-19, click here.
CT Scan
- There are no specific CT scan findings related to COVID-19-associated acute myocardial injury.
- To view the CT scan findings on COVID-19, click here.
MRI
- There are no specific MRI findings related to COVID-19-associated acute myocardial injury.
- To view the MRI findings on COVID-19, click here.
Other Imaging Findings
- There are no other imaging findings related to COVID-19-associated acute myocardial injury.
- To view other imaging findings on COVID-19, click here.
Other Diagnostic Findings
- There are no other diagnostic studies related to COVID-19-associated acute myocardial injury.
- To view other diagnostic studies for COVID-19, click here.
Treatment
Medical Therapy
- There are no specific treatments, and treatment varies depending upon presentation, please click on the conditions to see the management.[62]
- (COVID-19-associated myocarditis
- COVID-19-associated myocardial infarction
- COVID-19-associated heart failure
- COVID-19-associated arrhythmia and conduction system disease
- COVID-19-associated cardiogenic shock
- COVID-19-associated cardiac arrest
- COVID-19-associated pericarditis
- COVID-19-associated spontaneous coronary artery dissection
- To view medical treatment for COVID-19, click here.
Surgery
- There is no established surgical intervention for the treatment of COVID-19-associated acute myocardial injury.
Primary Prevention
- There are no available vaccines against COVID-19 and studies are going on for finding an effective vaccine.
- Other primary prevention strategies include measures to reduce the occurrence of myocardial injury among COVID-19 patients. Recent studies have suggested the use of medications improving microcirculation, especially for the high-risk group such as males, smokers, diabetic patients, and patients with established cardiovascular disease comorbidities.[63]
- For Risk factors associated with COVID-19 please click here
Secondary Prevention
- There are no established measures for the secondary prevention of COVID-19-associated myocardial injury.
References
- ↑ Khan AA (March 1980). "Preliminary in vitro study of diazepam and droperidol on oestrus rat uterus". Br J Anaesth. 52 (3): 349–54. doi:10.1093/bja/52.3.349. PMID 7189403.
- ↑ Khan AA (March 1980). "Preliminary in vitro study of diazepam and droperidol on oestrus rat uterus". Br J Anaesth. 52 (3): 349–54. doi:10.1093/bja/52.3.349. PMID 7189403.
- ↑ "www.cdc.gov" (PDF).
- ↑ Huang, Chaolin; Wang, Yeming; Li, Xingwang; Ren, Lili; Zhao, Jianping; Hu, Yi; Zhang, Li; Fan, Guohui; Xu, Jiuyang; Gu, Xiaoying; Cheng, Zhenshun; Yu, Ting; Xia, Jiaan; Wei, Yuan; Wu, Wenjuan; Xie, Xuelei; Yin, Wen; Li, Hui; Liu, Min; Xiao, Yan; Gao, Hong; Guo, Li; Xie, Jungang; Wang, Guangfa; Jiang, Rongmeng; Gao, Zhancheng; Jin, Qi; Wang, Jianwei; Cao, Bin (2020). "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China". The Lancet. 395 (10223): 497–506. doi:10.1016/S0140-6736(20)30183-5. ISSN 0140-6736.
- ↑ "Key Points About Myocardial Injury and Cardiac Troponin in COVID-19 - American College of Cardiology".
- ↑ "Key Points About Myocardial Injury and Cardiac Troponin in COVID-19 - American College of Cardiology".
- ↑ "Key Points About Myocardial Injury and Cardiac Troponin in COVID-19 - American College of Cardiology".
- ↑ "Fourth Universal Definition of Myocardial Infarction - American College of Cardiology".
- ↑ Wei, Haiming; Xu, Xiaoling; Tian, Zhigang; Sun, Rui; Qi, Yingjie; Zhao, Changcheng; Wang, Dongsheng; Zheng, Xiaohu; Fu, Binqing; Zhou, Yonggang (2020). "Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients". National Science Review. 7 (6): 998–1002. doi:10.1093/nsr/nwaa041. ISSN 2095-5138.
- ↑ Kubasiak, L. A.; Hernandez, O. M.; Bishopric, N. H.; Webster, K. A. (2002). "Hypoxia and acidosis activate cardiac myocyte death through the Bcl-2 family protein BNIP3". Proceedings of the National Academy of Sciences. 99 (20): 12825–12830. doi:10.1073/pnas.202474099. ISSN 0027-8424.
- ↑ Han, Huan; Yang, Lan; Liu, Rui; Liu, Fang; Wu, Kai-lang; Li, Jie; Liu, Xing-hui; Zhu, Cheng-liang (2020). "Prominent changes in blood coagulation of patients with SARS-CoV-2 infection". Clinical Chemistry and Laboratory Medicine (CCLM). 58 (7): 1116–1120. doi:10.1515/cclm-2020-0188. ISSN 1437-4331.
- ↑ Tavazzi, Guido; Pellegrini, Carlo; Maurelli, Marco; Belliato, Mirko; Sciutti, Fabio; Bottazzi, Andrea; Sepe, Paola Alessandra; Resasco, Tullia; Camporotondo, Rita; Bruno, Raffaele; Baldanti, Fausto; Paolucci, Stefania; Pelenghi, Stefano; Iotti, Giorgio Antonio; Mojoli, Francesco; Arbustini, Eloisa (2020). "Myocardial localization of coronavirus in COVID‐19 cardiogenic shock". European Journal of Heart Failure. 22 (5): 911–915. doi:10.1002/ejhf.1828. ISSN 1388-9842.
- ↑ Zhou, Fei; Yu, Ting; Du, Ronghui; Fan, Guohui; Liu, Ying; Liu, Zhibo; Xiang, Jie; Wang, Yeming; Song, Bin; Gu, Xiaoying; Guan, Lulu; Wei, Yuan; Li, Hui; Wu, Xudong; Xu, Jiuyang; Tu, Shengjin; Zhang, Yi; Chen, Hua; Cao, Bin (2020). "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study". The Lancet. 395 (10229): 1054–1062. doi:10.1016/S0140-6736(20)30566-3. ISSN 0140-6736.
- ↑ Tavazzi, Guido; Pellegrini, Carlo; Maurelli, Marco; Belliato, Mirko; Sciutti, Fabio; Bottazzi, Andrea; Sepe, Paola Alessandra; Resasco, Tullia; Camporotondo, Rita; Bruno, Raffaele; Baldanti, Fausto; Paolucci, Stefania; Pelenghi, Stefano; Iotti, Giorgio Antonio; Mojoli, Francesco; Arbustini, Eloisa (2020). "Myocardial localization of coronavirus in COVID‐19 cardiogenic shock". European Journal of Heart Failure. 22 (5): 911–915. doi:10.1002/ejhf.1828. ISSN 1388-9842.
- ↑ Meng, Xiao; Yang, Jianmin; Dong, Mei; Zhang, Kai; Tu, Eric; Gao, Qi; Chen, Wanjun; Zhang, Cheng; Zhang, Yun (2015). "Regulatory T cells in cardiovascular diseases". Nature Reviews Cardiology. 13 (3): 167–179. doi:10.1038/nrcardio.2015.169. ISSN 1759-5002.
- ↑ Komarowska, Izabela; Coe, David; Wang, Guosu; Haas, Robert; Mauro, Claudio; Kishore, Madhav; Cooper, Dianne; Nadkarni, Suchita; Fu, Hongmei; Steinbruchel, Daniel A.; Pitzalis, Costantino; Anderson, Graham; Bucy, Pat; Lombardi, Giovanna; Breckenridge, Ross; Marelli-Berg, Federica M. (2015). "Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release". Immunity. 42 (6): 1087–1099. doi:10.1016/j.immuni.2015.05.014. ISSN 1074-7613.
- ↑ Komarowska, Izabela; Coe, David; Wang, Guosu; Haas, Robert; Mauro, Claudio; Kishore, Madhav; Cooper, Dianne; Nadkarni, Suchita; Fu, Hongmei; Steinbruchel, Daniel A.; Pitzalis, Costantino; Anderson, Graham; Bucy, Pat; Lombardi, Giovanna; Breckenridge, Ross; Marelli-Berg, Federica M. (2015). "Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release". Immunity. 42 (6): 1087–1099. doi:10.1016/j.immuni.2015.05.014. ISSN 1074-7613.
- ↑ Zhou, Fei; Yu, Ting; Du, Ronghui; Fan, Guohui; Liu, Ying; Liu, Zhibo; Xiang, Jie; Wang, Yeming; Song, Bin; Gu, Xiaoying; Guan, Lulu; Wei, Yuan; Li, Hui; Wu, Xudong; Xu, Jiuyang; Tu, Shengjin; Zhang, Yi; Chen, Hua; Cao, Bin (2020). "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study". The Lancet. 395 (10229): 1054–1062. doi:10.1016/S0140-6736(20)30566-3. ISSN 0140-6736.
- ↑ Han, Seongwook; Kim, Hyun Ah; Kim, Jin Young; Kim, In-Cheol (2020). "COVID-19-related myocarditis in a 21-year-old female patient". European Heart Journal. 41 (19): 1859–1859. doi:10.1093/eurheartj/ehaa288. ISSN 0195-668X.
- ↑ Mehta, Puja; McAuley, Daniel F; Brown, Michael; Sanchez, Emilie; Tattersall, Rachel S; Manson, Jessica J (2020). "COVID-19: consider cytokine storm syndromes and immunosuppression". The Lancet. 395 (10229): 1033–1034. doi:10.1016/S0140-6736(20)30628-0. ISSN 0140-6736.
- ↑ Zhou, Peng; Yang, Xing-Lou; Wang, Xian-Guang; Hu, Ben; Zhang, Lei; Zhang, Wei; Si, Hao-Rui; Zhu, Yan; Li, Bei; Huang, Chao-Lin; Chen, Hui-Dong; Chen, Jing; Luo, Yun; Guo, Hua; Jiang, Ren-Di; Liu, Mei-Qin; Chen, Ying; Shen, Xu-Rui; Wang, Xi; Zheng, Xiao-Shuang; Zhao, Kai; Chen, Quan-Jiao; Deng, Fei; Liu, Lin-Lin; Yan, Bing; Zhan, Fa-Xian; Wang, Yan-Yi; Xiao, Geng-Fu; Shi, Zheng-Li (2020). "A pneumonia outbreak associated with a new coronavirus of probable bat origin". Nature. 579 (7798): 270–273. doi:10.1038/s41586-020-2012-7. ISSN 0028-0836.
- ↑ Wan, Yushun; Shang, Jian; Graham, Rachel; Baric, Ralph S.; Li, Fang; Gallagher, Tom (2020). "Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus". Journal of Virology. 94 (7). doi:10.1128/JVI.00127-20. ISSN 0022-538X.
- ↑ Zhou, Peng; Yang, Xing-Lou; Wang, Xian-Guang; Hu, Ben; Zhang, Lei; Zhang, Wei; Si, Hao-Rui; Zhu, Yan; Li, Bei; Huang, Chao-Lin; Chen, Hui-Dong; Chen, Jing; Luo, Yun; Guo, Hua; Jiang, Ren-Di; Liu, Mei-Qin; Chen, Ying; Shen, Xu-Rui; Wang, Xi; Zheng, Xiao-Shuang; Zhao, Kai; Chen, Quan-Jiao; Deng, Fei; Liu, Lin-Lin; Yan, Bing; Zhan, Fa-Xian; Wang, Yan-Yi; Xiao, Geng-Fu; Shi, Zheng-Li (2020). "A pneumonia outbreak associated with a new coronavirus of probable bat origin". Nature. 579 (7798): 270–273. doi:10.1038/s41586-020-2012-7. ISSN 0028-0836.
- ↑ Zhou, Peng; Yang, Xing-Lou; Wang, Xian-Guang; Hu, Ben; Zhang, Lei; Zhang, Wei; Si, Hao-Rui; Zhu, Yan; Li, Bei; Huang, Chao-Lin; Chen, Hui-Dong; Chen, Jing; Luo, Yun; Guo, Hua; Jiang, Ren-Di; Liu, Mei-Qin; Chen, Ying; Shen, Xu-Rui; Wang, Xi; Zheng, Xiao-Shuang; Zhao, Kai; Chen, Quan-Jiao; Deng, Fei; Liu, Lin-Lin; Yan, Bing; Zhan, Fa-Xian; Wang, Yan-Yi; Xiao, Geng-Fu; Shi, Zheng-Li (2020). "A pneumonia outbreak associated with a new coronavirus of probable bat origin". Nature. 579 (7798): 270–273. doi:10.1038/s41586-020-2012-7. ISSN 0028-0836.
- ↑ 25.0 25.1 25.2 Metkus TS, Sokoll LJ, Barth AS, Czarny MJ, Hays AG, Lowenstein CJ, Michos ED, Nolley EP, Post WS, Resar JR, Thiemann DR, Trost JC, Hasan RK (February 2021). "Myocardial Injury in Severe COVID-19 Compared With Non-COVID-19 Acute Respiratory Distress Syndrome". Circulation. 143 (6): 553–565. doi:10.1161/CIRCULATIONAHA.120.050543. PMC 7864609 Check
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|pmc=value (help). PMID 32512122 Check|pmid=value (help). - ↑ Bavishi C, Bonow RO, Trivedi V, Abbott JD, Messerli FH, Bhatt DL (June 2020). "Acute myocardial injury in patients hospitalized with COVID-19 infection: A review". Prog Cardiovasc Dis. doi:10.1016/j.pcad.2020.05.013. PMC 7274977 Check
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|pmc=value (help). PMID 32211816 Check|pmid=value (help). - ↑ Lippi G, Lavie CJ, Sanchis-Gomar F (March 2020). "Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence from a meta-analysis". Prog Cardiovasc Dis. doi:10.1016/j.pcad.2020.03.001. PMC 7127395 Check
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|pmc=value (help). PMID 32211816 Check|pmid=value (help). - ↑ 46.0 46.1 Bodini G, Demarzo MG, Casagrande E, De Maria C, Kayali S, Ziola S, Giannini EG (May 2020). "Concerns related to COVID-19 pandemic among patients with inflammatory bowel disease and its influence on patient management". Eur. J. Clin. Invest. 50 (5): e13233. doi:10.1111/eci.13233. PMC 7235524 Check
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|pmc=value (help). PMID 32317203 Check|pmid=value (help). - ↑ Guzik TJ, Mohiddin SA, Dimarco A, Patel V, Savvatis K, Marelli-Berg FM, Madhur MS, Tomaszewski M, Maffia P, D'Acquisto F, Nicklin SA, Marian AJ, Nosalski R, Murray EC, Guzik B, Berry C, Touyz RM, Kreutz R, Wang DW, Bhella D, Sagliocco O, Crea F, Thomson EC, McInnes IB (April 2020). "COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options". Cardiovasc. Res. doi:10.1093/cvr/cvaa106. PMC 7197627 Check
|pmc=value (help). PMID 32352535 Check|pmid=value (help). - ↑ Guo, Tao; Fan, Yongzhen; Chen, Ming; Wu, Xiaoyan; Zhang, Lin; He, Tao; Wang, Hairong; Wan, Jing; Wang, Xinghuan; Lu, Zhibing (2020). "Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19)". JAMA Cardiology. 5 (7): 811. doi:10.1001/jamacardio.2020.1017. ISSN 2380-6583.
- ↑ Bonow, Robert O.; Fonarow, Gregg C.; O’Gara, Patrick T.; Yancy, Clyde W. (2020). "Association of Coronavirus Disease 2019 (COVID-19) With Myocardial Injury and Mortality". JAMA Cardiology. 5 (7): 751. doi:10.1001/jamacardio.2020.1105. ISSN 2380-6583.
- ↑ Guo, Tao; Fan, Yongzhen; Chen, Ming; Wu, Xiaoyan; Zhang, Lin; He, Tao; Wang, Hairong; Wan, Jing; Wang, Xinghuan; Lu, Zhibing (2020). "Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19)". JAMA Cardiology. doi:10.1001/jamacardio.2020.1017. ISSN 2380-6583.
- ↑ 53.0 53.1 Bavishi C, Bonow RO, Trivedi V, Abbott JD, Messerli FH, Bhatt DL (June 2020). "Acute myocardial injury in patients hospitalized with COVID-19 infection: A review". Prog Cardiovasc Dis. doi:10.1016/j.pcad.2020.05.013. PMC 7274977 Check
|pmc=value (help). PMID 32512122 Check|pmid=value (help). - ↑ Bavishi C, Bonow RO, Trivedi V, Abbott JD, Messerli FH, Bhatt DL (June 2020). "Acute myocardial injury in patients hospitalized with COVID-19 infection: A review". Prog Cardiovasc Dis. doi:10.1016/j.pcad.2020.05.013. PMC 7274977 Check
|pmc=value (help). PMID 32512122 Check|pmid=value (help). - ↑ Wu, Zunyou; McGoogan, Jennifer M. (2020). "Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China". JAMA. 323 (13): 1239. doi:10.1001/jama.2020.2648. ISSN 0098-7484.
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- ↑ Guo, Tao; Fan, Yongzhen; Chen, Ming; Wu, Xiaoyan; Zhang, Lin; He, Tao; Wang, Hairong; Wan, Jing; Wang, Xinghuan; Lu, Zhibing (2020). "Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19)". JAMA Cardiology. doi:10.1001/jamacardio.2020.1017. ISSN 2380-6583.
- ↑ Bavishi C, Bonow RO, Trivedi V, Abbott JD, Messerli FH, Bhatt DL (June 2020). "Acute myocardial injury in patients hospitalized with COVID-19 infection: A review". Prog Cardiovasc Dis. doi:10.1016/j.pcad.2020.05.013. PMC 7274977 Check
|pmc=value (help). PMID 32512122 Check|pmid=value (help). - ↑ "Key Points About Myocardial Injury and Cardiac Troponin in COVID-19 - American College of Cardiology".
- ↑ Montone, Rocco A; Iannaccone, Giulia; Meucci, Maria Chiara; Gurgoglione, Filippo; Niccoli, Giampaolo (2020). "Myocardial and Microvascular Injury Due to Coronavirus Disease 2019". European Cardiology Review. 15. doi:10.15420/ecr.2020.22. ISSN 1758-3764.
COVID 19