COVID-19-associated pulmonary hypertension: Difference between revisions
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OR | OR | ||
Cardiac MRI is one of the most accurate method in the diagnosis of pulmonary hypertension . Findings on MRI suggestive of pulmonary hypertension include : | |||
assessment the anatomy of the pulmonary arteries | |||
assessment of pulmonary blood flow | |||
assessment of right ventricular size, morphology and function | |||
OR | OR | ||
There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3]. | There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication | ||
Cardiac MR imaging is one of the most accurate methods for assessing right ventricular size, morphology, and function (4,9,11). It can also be used to assess the anatomy of the pulmonary arteries and pulmonary blood flow (7). In our practice, cardiac MR imaging is often used to evaluate the effectiveness of treatment for PH (surgery or medication) (12). In other words, cardiac MR imaging is used to make sure that the right ventricle is not showing signs of failure (eg, dilatation or reduced ejection fraction) that would warrant additional intervention or medication. | |||
3]. | |||
===Other Imaging Findings=== | ===Other Imaging Findings=== |
Revision as of 07:33, 3 July 2020
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Zand,MD
Synonyms and keywords:
Overview
Pulmonary hypertention (PH) is determined as an increase in mean pulmonary arterial pressure(mPAP) of 25 mm Hg or greater at rest.Pulmonary arterial remodeling and vasoconstriction prompting to increase pulmonary artery pressure and finally right heart failure..Few cases of covid 19 with PH were found and it seems due to keeping social distance and quarantine the number of cases are understimated. PH is a rare disease and Studies about PH during SARS -COV disease in 2003 implied the role of inflammation in this process.
Historical Perspective
The association between COVID infection and pulmonary hypertension was made in 2004 during eidemic SARS-COVID
Classification
- Pulmonary hypertension in covid19 may be classified into two subtype:
- Pulmonary hypertension due to lung disease or hypoxia
- Microvascular thromboembolic pulmonary hypertension
Pathophysiology
- .The SARS-CoV-2 and SARS-CoV virus genomes are highly similar, and patients infected with these viruses have common pathological features.(8)
- The pathogenesis of PH in covid19 is characterized by lack of angiotensin converting enzyme 2( ACE2 )and local endothelial cell dysfunction .(lancet rheumatology ,dennis mc ganagle)
- Renin angiotensin system (RAS) is responsible for hemeostasis of blood pressure and electrolyte balance and inflammatory response. Renin is a protease which is produced in kidney and cleaves angiotensinogen to angiotensin 1.Then angiotensin convertase enzyme(ACE) cleaves angiotensin 1 to angiotensin 2. Angiotensin2 is a key factor of RAS and has two receptors including type1 and type2 [1].
- angiotensin-converting enzyme 2 (ACE2), and neprilysin hydrolyze angiotensin 2 to vasodilatory agents including Ang1–7, Ang III, Ang IV, and Ang A .[2]
- Angiotensin-converting enzyme 2 (ACE2) was a receptor of spike protein on SARS corona virus in epithelial cell and after attaching virus the activity of enzyme(ACE2) was decreased and then virus spread quickly[3](12)
- Lack of ACE2 causes elevation in angiotensin2 level causing vascular permeability and lung edema and neutrophil infiltration and further lung deterioration.
- ACE2 has anti inflammation effect and protected the lung from acute lung injury.(4)
- Phosphorilized ACE2 is much more stable form in which converts angiotensin 2 to angiotensin 1-7 and increases endothelial nitric oxide synthase-derived NO bioavailability ,
- then lack of phosphorilized ACE2 caused vasoconstriction and pulmonary hypertension (5)
- Nitric oxide inhalation for SARS-corona patients was correlated with vasodilation and relaxation of pulmonary artery, reduction in pulmonary artery pressure and improvement in arterial oxygenation. (6)
- Endothelin-1 caused downregulated ACE2 expression in lung epithelial cells and pulmonary vasoconstriction.(7)
- On histopathological analysis ,pulmonary wall edema,hyalin thrombosis , inflammatory cell infiltration of pulmonary microvasculature,pulmonary infarction , vessle thrombosis due to diffuse alveolar damage and septal inflammation were characteristic findings of PH in SARS-COV and covid19.(9)
Causes
Factors contributing to constriction and microthrombotic formation in pulmonary artery in covid 19 include:
- Diffuse alveolar and interestitial inflammation causing hypoxia . Hypoxia(14) may induce endothelial dysfunction and activation of coagulation cascade in small vessles
- ACE2 receptor expression downregulation after attaching the sparkle site of covid19 to pneumocytes type2
- Activation of innate coagulation cascade with older age
- (15)Mechanical ventilation may induce immune micro thrombosis in small arteries
- Bacterial super infection
Differentiating COVID-19-associated pulmonary hypertension from other Diseases
- Pulmonary intravascular coagulopathy causing pulmonary hypertention in covid19 must be differentiated from disseminated intravascular coagulation(DIC) based on clinical features and lab data :(lancet rheumatology)
Disseminated intravascular coagulopathy | Pulmonary intravascular coagulopathy | |
Onset | Acute | Subacute |
Pulmonary involvement (%) | 50% | 100% |
Thrombosis | Multi-organ clotting | Mainly lung (occasional CNS and peripheral thrombosis reported; related to DIC evolution?) |
Bleeding | Generalised | Intrapulmonary microhaemorrhage |
Liver function | Decreased synthetic function including fibrinogen and other clotting factors; raised transaminase +++ | Preservation of liver synthetic function; +/− |
Anaemia | +++ | − |
Thrombocytopenia | +++ | Normal or low |
Immune cell cytopenia | ++ | No but lymphopenia is a feature of COVID-19 in general |
Creatine kinase | + (skeletal and cardiac origin) | + (worse prognosis) |
Troponin T | + | ++ with high levels associated with worse outcome |
Elevated prothrombin time or activated partial thromboplastin time | +++/+++ | + or normal |
Fibrinogen levels | Decreased | Normal or slight increase |
Fibrin degradation products or D-dimer | Increased | Increased |
C-reactive protein | Elevated | Elevated |
Ferritin elevation | +++ | Elevated |
Hypercytokinaemia | +++ | ++ |
Epidemiology and Demographics
- Pulmonary hypertension in covid19 commonly was seen in older age individuals.
- There is no racial predilection to pulmonary hypertension in covid19.
- male are more commonly affected by covid19 than female ,therefore, the prevalence of pulmonary hypertension induced by covid19 in higher in male gender.
Risk Factors
Common risk factors in the development of pulmonary hypertention in covid 19 are male sex, hypertension, obesity, and diabetes (lancet rheumato)
Screening
There is insufficient evidence to recommend routine screening for pulmonary hypertension in covid19.
Natural History, Complications, and Prognosis
- Severe COVID-19 sepsis increase inflammatory markers including (IL)-1,(IL) -6 and tumor necrosis factor and ferritin concentration which cause pulmonary endothelial dysfunction and thromboinflammatory process.(16)
- Hypoxia in COVID-19 pneumonia will cause endothelial dysfunction and expression of active tissue factor on endothelium , macrophage , neutrophils, and finally activation of coagulation cascade
- Prognosis is generally poor in older patients and high level of fibrin degeredated factors, including, D-dimer and cardiac troponinT due to right ventricular failure.(11)
Additionally, the MAS-like picture associated with COVID-19 pneumonia will trigger expression of active tissue factor, both on endothelial cells and on activated infiltrating macrophages and neutrophils.
50
The net effect will be local presentation of blood-borne tissue factor within the lungs, which will further amplify activation of the coagulation cascade. Importantly, endothelial cell disruption, tissue factor expression, and activation of the coagulation cascade will all be progressively exacerbated by development of local hypoxia,
51
establishing a deleterious positive thromboinflammatory feedback loop within the small vessels of the lungs with thrombosis and haemorrhage (figure 3). Beyond the coagulopathic changes occurring within the pulmonary vasculature, a study of bronchoalveolar lavage showed that both severe pneumonia and ARDS are associated with enhanced thrombin generation and fibrin deposition within the bronchoalveolar
a study of bronchoalveolar lavage showed that both severe pneumonia and ARDS are associated with enhanced thrombin generation and fibrin deposition within the bronchoalveolar system.
52
These changes correlate with severity of inflammation
53
and are primarily driven by upregulation of tissue factor expression within the alveoli, coupled with a reduction in fibrinolysis induced by plasminogen activation inhibitor 1.
54
The biological mechanisms responsible for the extremely elevated plasma D-dimer concentrations in patients with severe COVID-19, together with the marked variations observed between individuals, are unclear. Nonetheless, these data clearly suggest hyperactive fibrinolysis with increased plasmin generation. Collectively, these findings have led to the suggestion that elevated plasmin (and plasminogen) concentrations might represent a risk factor for COVID-19 susceptibility.
55
Diagnosis
Diagnostic Study of Choice
The diagnosis of pulmonary hypertension is made when at least three of the following diagnostic criteria are met:
In right heart catheterization(RHC) mPAP≥25 mmHg,pulmonary artery wedge pressure≤15 mmHg, Pulmonary vascular resistance ≥3 wood units
History and Symptoms
The most common symptoms of pulmonary hypertension include exertional dyspnea , chest pain,fatigue,light headness.Less common symptoms include syncope, abdominal distention,lower extremity edema which are seen in advanced disease and right ventricular failure.
Physical Examination
- Physical examination in PH may be remarkable for:
- Rale,dulness or decreased breath sound due to pulmonary congestion or effusion
- central cyanosis due to hypoxia
- Holosystolic murmur increased with inspiration due to tricuspid regurgitation (TR)
- Diastolic murmur due to pulmonary regurgitation
- Hepatojugular reflux
- Right ventricular S3 due to RV dysfunction
- Distention of jugular veins due to RV dysfunction and TR
- Peripheral edema and ascites
- Low blood Pressure , diminished pulse pressure , cool extremities due to reduced cardiac out put ,prepheral vasoconstriction
Laboratory Findings
- laboratory findings consistent with the diagnosis of pulmonary hypertension in covid19 include:(lancet rheumato)
- Increased D-dimer(due to pulmonary vascular bed thrombosis with fibrinolysis)
- Elevated cardiac enzyme concentration due to right ventriclular strain induced by pulmonary hypertention
- Normal fibrinigen and platelet level
Electrocardiogram
An ECG may be helpful in the diagnosis of pulmonary hypertension. Findings on an ECG suggestive pulmonary hypertension include right atrial enlargement, right axis deviation,right ventricular enlargement with strain pattern
X-ray
An x-ray may be helpful in the diagnosis of pulmonary hypertension in covid 19. Findings on an x-ray suggestive of pulmonary hypertension include
- Enlarged main pulmonary artery,
- Prunning or attenuation of peripheral vasculture and
- Right ventricular enlargement specially in lateral view
- With other evidence of lung involvement in covid19
Echocardiography or Ultrasound
Echocardiography is helpful in the diagnosis of pulmonary hypertension . Findings on an echocardiography suggestive of pulmonary hypertension include:
- right atrial enlargement,
- right ventricular enlargement and dysfunction,
- small left side chambers,
- interventricular setal flattening,
- tricuspid regurgitation
CT scan
There are no CT scan findings associated with [disease name].
OR
[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
MRI
There are no MRI findings associated with [disease name].
OR
Cardiac MRI is one of the most accurate method in the diagnosis of pulmonary hypertension . Findings on MRI suggestive of pulmonary hypertension include :
assessment the anatomy of the pulmonary arteries
assessment of pulmonary blood flow
assessment of right ventricular size, morphology and function
OR
There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication
Cardiac MR imaging is one of the most accurate methods for assessing right ventricular size, morphology, and function (4,9,11). It can also be used to assess the anatomy of the pulmonary arteries and pulmonary blood flow (7). In our practice, cardiac MR imaging is often used to evaluate the effectiveness of treatment for PH (surgery or medication) (12). In other words, cardiac MR imaging is used to make sure that the right ventricle is not showing signs of failure (eg, dilatation or reduced ejection fraction) that would warrant additional intervention or medication.
3].
Other Imaging Findings
There are no other imaging findings associated with [disease name].
OR
[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
Other Diagnostic Studies
There are no other diagnostic studies associated with [disease name].
OR
[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].
Treatment
Medical Therapy
- The mainstay of therapy for pulmonary hypertension in covid19 is(10)(13)
- Pulmonary vasodilator
- Supplement oxygen for correction of hypoxia to maintain oxygen saturation above %90 ,
- Correction of hypotension with fluild and inotropic agents to avoid decreased RV coronary perfusion and RV ejection.
- Correction of acidosis, hypercarbia,hypothermia, hypervolemia
- Intubation is not recommended due to effect of positive pressure ventilation on increased RV preload and vasodilatory effect of sedation agents impending systemic hypotension and hemodynamic collapse.
- If intubation is indicated , vasoactive agent should be given before anesthesia. Etomidate is recommended for general anesthesia due to little effect on cardiac contractiliy and vascular tone.
- Ventilator should be set with low tidal volumes and moderate positive end expiratory pressure for minimum air way pressure and sufficient oxygenation and ventilation.
Surgery
Surgical intervention is not recommended for the management of pulmonary hypertension in covid 19
Primary Prevention
Effective measures for the primary prevention of PH and covid19 include keeping social distancing and maintaning the medication which was used for pulmonary hypertension.
Secondary Prevention
There are no established measures for the secondary prevention of pulmonary hypertension in covid19
References
4.Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, Yang P, Sarao R, Wada T, Leong-Poi H, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 2005; 436:112–116
5.Zhang J, Dong J, Martin M, et al. AMP-activated Protein Kinase Phosphorylation of Angiotensin-Converting Enzyme 2 in Endothelium Mitigates Pulmonary Hypertension. Am J Respir Crit Care Med. 2018;198(4):509-520. doi:10.1164/rccm.201712-2570OC.
6.Chen L, Liu P, Gao H, et al. Inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: a rescue trial in Beijing. Clin Infect Dis. 2004;39(10):1531-1535. doi:10.1086/425357
7.Zhang, Hongliang, et al. "Endothelin-1 downregulates angiotensin-converting enzyme-2 expression in human bronchial epithelial cells." Pharmacology 91.5-6 (2013): 297-304.
8.Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-733. doi:10.1056/NEJMoa2001017
9.Fox SE Pulmonary and cardiac pathology in Covid-19: the first autopsy series from New Orleans. medRxiv. 2020; (published online April 10.) (preprint).DOI: 10.1101/2020.04.06.20050575
10.APA Gordon, Clairea; Collard, Charles Da,b; Pan, Weia,b Intraoperative management of pulmonary hypertension and associated right heart failure, Current Opinion in Anaesthesiology: February 2010 - Volume 23 - Issue 1 - p 49-56
doi: 10.1097/ACO.0b013e3283346c51
11.Zhou F Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; 395: 1054-1062
12.Li W, Moore MJ, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450-454. doi:10.1038/nature02145
13.Pritts CD, Pearl RG. Anesthesia for patients with pulmonary hypertension. Curr Opin Anaesthesiol. 2010;23(3):411-416. doi:10.1097/ACO.0b013e32833953fb
14.Ten VS Endothelial response to hypoxia: physiologic adaptation and pathologic dysfunction.Curr Opin Crit Care. 2002; 8: 242-250
15.Engelmann BThrombosis as an intravascular effector of innate immunity.Nat Rev Immunol. 2013; 13: 34-45
16.Levi M Coagulation and sepsis.Thromb Res. 2017; 149: 38-44