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The cosevast study outcome: Evidence of COVID-19 severity proportionate to surge in arterial stiffness
Indian Journal of Critical Care Medicine ; 25(SUPPL 1):S108-S111, 2021.
Article in English | EMBASE | ID: covidwho-1200284


It has been extensively highlighted that SARS-CoV-2 affects the RAS (renin-angiotensin system) and the angiotensinconverting enzyme-2 receptors play the most important role in the presentation of the COVID-19 disease.2-5 The ACE2 is type I membrane protein expressed on endothelial cells in the kidney, heart, gastrointestinal tract, blood vessels, and, importantly, lung AT2 alveolar epithelial cells, which are particularly prone to SARS-CoV-2 infection. As SARS-CoV-2 is a new coronavirus, and its cardiovascular complications and the underlying pathology is still emerging. However, it is accepted that the virus affects the total vasculature in the human body and this infection becomes a highly accelerated process for the target organ damage. In the case of acute cardiological manifestation, it is termed as Acute COVID-19 Cardiovascular Syndrome (ACovCS) by the American Heart Association's white paper.6 European Society of Cardiology (ESC) has published a detailed review paper 7 on the involvement of various cardiovascular target organs in COVID-19 disease. This review clearly establishes a close two-way relationship between COVID-19 disease and all cardiovascular diseases (CVD). The prognosis is even worse in patients with preexisting cardiovascular system involvement. Cardiovascular involvement in COVID-19 is seen as a key manifestation. The best way to assess endothelial dysfunction is an assessment of its clinical manifestation, i.e., an increase in arterial stiffness. There have been multiple in vitro and in vivo studies that have shown that the vascular endothelium is an important factor in setting the vascular tone and endothelial dysfunction leads to arterial stiffness.8 Arterial stiffness and enhanced wave reflections are markers of cardiovascular disease and independent predictors of cardiovascular risk.9-12 Stiffening of the large arteries and enhanced wave reflections lead to increased left ventricular (LV) afterload, disturbed coronary perfusion, and mechanical fatigue of the arterial wall.13 The relationship between systemic inflammation and arterial stiffness is well established in the literature.14 The cause-and-effect relationship that acute systemic inflammation leads to deterioration of large-artery stiffness. Findings in study15 on induced inflammation have shown that an acute inflammation caused a temporary increase in central blood pressure and arterial stiffness in terms of pulse wave velocity. This implies the increased risk of cardiovascular events associated with acute systemic inflammation in the COVID-19. COVID-19 diseaserelated worldwide research and proposed mechanisms pointed to pathophysiological involvement of endothelial dysfunction and arterial wall compromise. However, there was no empirical evidence of the functional compromise of arterial walls. Hence, a study was urgently needed to study an increase in arterial stiffness in COVID-19 patients due to systemic inflammation to stratify the risk and mitigate further cardiovascular damage with guided therapeutic treatment based on the severity of arterial stiffness. This pressing need is justified by a comprehensive review article16 published after the present study was envisaged. We hope that the findings from our study will fulfill the need to a large extent.




To study if the measurement of arterial stiffness using pulse wave velocity in mild-moderate and a severe group of COVID-19 patients can stratify cardiovascular risk. Secondary


To determine if initial measurements and subsequent changes in arterial stiffness can project the future course of the COVID-19 patient and hence predict the grade of clinical management a confirmed COVID-19 patient would require. Materials and


The present prospective nonrandomized observational study {titled - “To study the relationship of COVID-19 severity with arterial stiffness A prospective cross-sectional study” (“COSEVAST study”)} was conducted in the COVID-19 ICU, medical ICU, and various wards of dedicated COVID hospital at AIIMS, Patna, Bihar, India. The study protocol, informed consents, and other trial-related documents received the written approval of the Institutional Ethics Committee (IEC No. AIIMS/Pat/IEC/2020/595). The study design was registered with the Clinical Trials Registry of India (CTRI No. CTRI/2020/10/028489). All COVID-19 patients were subject to RT-PCR test and had a confirmed infection of the SARS-CoV-2 virus. Participants, after understanding the study protocol and procedures, gave their written informed consent for the study. The exclusion criteria were known history of any of these diseases - diabetes mellitus (DM), hypertension (HTN), CAD, stroke, neuropathy, PAD, nephropathy, MI, pregnancy, peripheral edema or inflammation, cardiac arrhythmia, and any preexisting cardiovascular disorder. Patient categorization The selected patients after fulfilling the inclusion criteria were grouped into three categories - mild, moderate, and severe category based on the latest NIH Guidelines 27 as follows •Mild category Individuals with mild signs and symptoms like fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, loss of taste and smell but who do not have shortness of breath, dyspnea, or abnormal chest imaging. •Moderate category Individuals who show evidence of lower respiratory disease during clinical assessment or imaging and who have a saturation of oxygen (SpO2) ≥ 94% on room air at sea level. •Severe category Individuals who have a saturation of oxygen (SpO2) < 94% on room air at sea level, a respiratory rate of >30 breaths/minute, PaO2/FiO2 <300 mm Hg, or lung infiltrates The range of treatment protocols followed in this study were based on our institutional standard operating procedure (SOP) for the management of COVID-19 patients based on their clinical severity category and it included antivirals (remdesivir), broad-spectrum antibiotics, low-molecular-weight heparin (enoxaparin) immunomodulators (steroids, tocilizumab) and supportive management (oxygen via nasal cannula, face mask, non-rebreathing face mask;noninvasive or invasive mechanical ventilation;awake proning). Measures of arterial stiffness Arterial stiffness assessed by PWV (pulse wave velocity) correlates to the number of treated and non-treated cardiovascular risk factors, atherosclerotic events, and cardiovascular risk as predicted by the Framingham risk equations.17 PWV is also positively correlated with carotid intima-media thickness, a marker of atherosclerotic burden in the coronary arteries.18 With the awareness of arterial stiffness during the non-COVID era, clinicians have started adding measurement and treatment of underlying arterial stiffness in their clinical practice.19 International healthcare societies like the European Society of Hypertension (ESH) and European Society of Cardiology (ESC) have included PWV measurement in their 2003 guidelines for the management of hypertension.20,21 Aortic and brachial PWV22 and AIx23 are independently related to the levels of inflammation, suggesting that inflammation plays a role in the regulation of arterial stiffening. In this study, Arterial stiffness is primarily measured in terms of pulse wave velocity, which is a recognized gold standard. Pulse wave velocity, which is a relevant indicator of arterial stiffness, can be measured noninvasively with a variety of devices. However, since COVID-19 is a highly contagious disease, a fully automatic device with minimal contact, less exposure time, and proximity with the patient need to be maintained. It would be always challenging for an observer to conducting the entire test by wearing full personal protection equipment (PPE) kit. So, a test device that avoids close proximity, long exposure, and holding a probe while testing, was needed for the study. We found that the medical device PeriScope- (Manufactured by M/s. Genesis Medical Systems Pvt. Ltd., Hyderabad, India) was suitable as it fulfilled all the above requirements. PeriScope is a clinically validated and tested noninvasive medical device used to m asure Brachial Ankle PWV (baPWV) and derives the Carotid Femoral PWV (cfPWV), which is equivalent to aortic PWV.24 A population-based study with 3,969 subjects using “PeriScope” has established the role of arterial stiffness in various cardiovascular diseases (CVD).25 Aortic pressure values also have been established as surrogate markers for arterial stiffness. PeriScope estimates the Aortic Pressures and the Systolic Pressure Augmentation (AugP) at the root of the Aorta due to the increased arterial stiffness. The Pressure Augmentation Index (AIx) values found by PeriScope were compared with other internationally accepted noninvasive devices and found to be very accurate and highly comparable.26 All the tests were conducted as per the standard procedure given in the operator's manual of PeriScope. Electrocardiogram (ECG) electrodes were placed on the ventral surface of both wrists and medial side of ankles, and BP cuffs were wrapped on both upper arm brachial artery and tibial artery above ankles. All the ECG and pressure recordings were done automatically and data were stored in the personal computer for analysis. The built invalidated proprietary algorithm within the PeriScope PC software calculated the following parameters from the waveforms, which were stored in the computer for analysis - systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP), heart rate (HR), carotid-femoral pulse wave velocity (cfPWV), Est. Aortic root values of Systolic, Diastolic, Pulse, Mean Arterial Pressures and Systolic Pressure Augmentation (AugP) with Augmentation Index (AIx).

Full text: Available Collection: Databases of international organizations Database: EMBASE Document Type: Article Type of study: Ethical aspects / Evidence synthesis / Prognostic study / Risk factors Language: English Journal: Indian Journal of Critical Care Medicine Clinical aspect: Etiology / Prediction / Prognosis Year: 2021





Full text: Available Collection: Databases of international organizations Database: EMBASE Document Type: Article Type of study: Ethical aspects / Evidence synthesis / Prognostic study / Risk factors Language: English Journal: Indian Journal of Critical Care Medicine Clinical aspect: Etiology / Prediction / Prognosis Year: 2021