REVIEW ARTICLE


https://doi.org/10.5005/jp-journals-11005-0021
Science, Art and Religion
Volume 1 | Issue 2-4 | Year 2022

COVID-19: Cardiovascular Disorders


Emir Fazlibegović

Dzemal Bijedic University of Mostar, Mostar, Bosnia and Herzegovina

Corresponding Author: Emir Fazlibegović, Dzemal Bijedic University of Mostar, Mostar, Bosnia and Herzegovina, Phone: +387036318838, e-mail: emir.fazlibegovic@gmail.com

ABSTRACT

The coronavirus disease of 2019 (COVID-19) infection has spread all over the world and caused a global health and economic crisis, so we will talk about the “time before COVID” and probably the “time after COVID.” Although the virus most often attacks the respiratory system, respiratory diseases, especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are the main cause of mortality in patients with COVID-19 infection, followed by damage to the myocardium and complete cardiovascular system, which is a common finding in patients. The association between COVID-19 and acute myocardial infarction (AMI) is interpreted as impaired immunity with enhanced inflammatory response and development of endothelium with procoagulant disorders such as thrombosis and thromboembolism with sequelae on the heart, brain, pulmonary and peripheral arteries. Endothelial dysfunction develops with myocardial damage with the instability of atherosclerotic plaque, its fissure and rupture, and AMI. Comorbid conditions such as hypertension, diabetes, hyperlipidemia, and kidney disease further exacerbate the severity and outcome of the disease. Air pollution also significantly contributes to the clinical picture of the disease and complicates COVID-19 infection with the development of cardiovascular complications of the AMI, with cardiac decompensation, malignant cardiac arrhythmias, myocarditis, and pericarditis that contribute to clinical severity and mortality. There was a lower influx of patients to cardiology departments and coronary units, and emergency services during the epidemic wave by 30–48% depending on the region-country in the world, but also an increase in the severity of the clinical picture and higher mortality from cardiovascular disease (CVD). The reasons for this phenomenon are mostly unknown. It is assumed that it is a matter of fear, “lockdown,” self-isolation, and delay in attending the doctor, which prolongs the time of ischemia and loses the “golden hour” to reperfusion of AMI patients, which is also contributed by antiepidemic measures with percutaneous coronary intervention (PCI) testing and personal protection measures. Staff in cat laboratories prolong the door-balloon time and thus cause more serious heart damage.

SAŽETAK

Zaraza COVID-19 proširila se po cijelom svijetu i izazvala globalnu zdravstvenu i ekonomsku krizu, pa ćemo govoriti o “vremenu prije covida” i vjerojatno “vremenu nakon covida.” Iako virus najčešće napada dišni sustav, respiratorne bolesti, posebice SARS-CoV-2, glavni su uzrok smrtnosti oboljelih od infekcije COVID-19, a zatim slijede oštećenja miokarda i kompletnog kardiovaskularnog sustava, što je čest nalaz kod oboljelih. Povezanost između COVID-19 i akutnog infarkta miokarda (AIM) tumači se kao oslabljen imunitet s pojačanim upalnim odgovorom i razvojem endotela s prokoagulacijskim poremećajima kao što su troboza i tromboembolija s posljedicama na srcu, mozgu, plućnim i perifernim arterijama. Endotelna disfunkcija nastaje kod oštećenja miokarda s nestabilnošću aterosklerotskog plaka, njegovom fisurom i rupturom te AIM. Komorbidna stanja poput hipertenzije, dijabetesa, hiperlipidemije i bolesti bubrega dodatno pogoršavaju težinu i ishod bolesti. Zagađenje zraka također značajno pridonosi kliničkoj slici bolesti i komplicira infekciju COVID-19 razvojem kardiovaskularnih komplikacija AIM, sa srčanom dekompenzacijom, malignim srčanim aritmijama, miokarditisom i perikarditisom koji doprinose kliničkoj težini i mortalitetu. Zabilježen je manji priljev pacijenata na kardiološke odjele i koronarne jedinice te hitne službe tijekom epidemijskog vala za 30-48% ovisno o regiji-zemlji u svijetu, ali i povećanje težine kliničke slike i većeg mortaliteta od kardiovaskularnih bolesti. Razlozi ove pojave uglavnom su nepoznati. Pretpostavlja se da je riječ o strahu, “lockdownu,” samoizolaciji i kašnjenju liječnika, čime se produljuje vrijeme ishemije i gubi “zlatni sat” za reperfuziju bolesnika s AIM-om, čemu pridonose i anti -epidemijske mjere uz PCI testiranje i mjere osobne zaštite. osoblja u kat- laboratorijima što produljuje vrijeme vrata-balona (DB) i time ozbiljnija oštećenja srca.

How to cite this article: Fazlibegović E. COVID-19: Cardiovascular Disorders. Sci Arts Relig 2022;1(2-4):221-228.

Source of support: Nil

Conflict of interest: None

Keywords: Acute myocardial infarction, Cardiovascular disorders, Comorbidities, Coronavirus disease 2019.

INTRODUCTION

Coronovirus disease of 2019 infection first appeared in Wuhan, China, in December 2019. It quickly spread around the world as a pandemic, declared by the World Health Organization (WHO) on 11th March 2020, affecting over 124 million people with 2.7 million deaths (data from 22nd March 2021). The pandemic has caused major disruptions not only in the health systems of all countries but also in numerous social and economic disruptions. Antiepidemic measures and vaccinations have not been implemented to the expected extent, which has led to the development of anti-vaccination movements and conspiracy theories, which as such complicate the problem even more. COVID-19 infection has the characteristics of a systemic disease with a significant impact on the cardiovascular system.1

The World Heart Federation (WHF) has launched a study to investigate the effects of COVID-19 infection on the cardiovascular system in hospitalized patients with COVID-19 and the effects of cardiovascular risk factors on the course of CVD. The study register included 48,271 patients from all continents (mostly from Europe 52.1% and North America 39.9%), including Bosnia and Herzegovina. Preliminary data from a study from February 2021 on over 2,400 patients published at our International Scientific Symposium on 7th April 2021 in Mostar dedicated to COVID-19, which includes 4% of patients from Bosnia and Herzegovina, shows that the patients are dominated by younger men with comorbid conditions: hypertension in 45%, diabetes in 35%, CVD in 15%, cerebrovascular disease in 15%, noncardiovascular comorbidity in about 20%, and total mortality of 17.7%, of which 38% is sudden death.2

To date, there are some specifics of CVD caused by corona infection associated with myocardial damage with arrhythmias, heart failure (HF), endothelial dysfunction, and thromboembolic disease.1

PATHOPHYSIOLOGY

Pathophysiological explanations for the increased mortality of patients with COVID-19 infection are mainly related to the direct effects of the virus on heart muscle followed by myocyte damage due to the interaction of S-protein of the virus with ACE-2 receptor myocytes resulting in systemic inflammation and cytokine storm oxygen due to pulmonary inflammation on the one hand and myocyte damage on the other, plaque rupture and coronary thrombosis affecting shear endothelial inflammation and creating prothrombotic milieu with additional effects of various drugs (hydroxychloroquine and azithromycin that give proarrhythmic effects, as well as lopinavir and remdesivir as virostatics) given to patients and electrolyte imbalance as a result of a number of factors. All these factors, in addition to existing comorbid conditions, age, and the presence of other risk factors, contribute to higher mortality, which in the presence of hypertension is 2× higher (6%), 2× higher in diabetics (7%), and 3× higher in those with coronary artery disease. Cerebrovascular disease (10%).

COVID-19 infection is known to cause the most common respiratory disorders, with SARS-CoV-2 leading to interstitial edema and respiratory failure indicating oxygen and respiratory therapy.

X-ray changes in the lungs, ECG changes, and an increase in cardiac biomarkers greatly help us assess the degree of damage to the cardiovascular system (CVS). Highly sensitive cardiac troponins (hsTrI/T), NT proBNP, d-dimers, and nonspecific inflammatory factors such as C-reactive protein (CRP), leukocytes - Ly, platelets, prothrombin-prothrombin time, cytokines, and others are especially important.3

COVID-induced Myocardial Damage

The most common types of myocardial damage are myocardial infarction (MI)—ST-elevated myocardial infarction (STEMI) and non-ST elevated myocardial infarction (NSTEMI), namely:

  • Type 1 is probably caused by the systemic inflammatory response with plaque rupture and coronary thrombus, and myocardial necrosis and dysfunction, and “cytokine storm” leads to T-helper lymphocyte imbalance (TH1/TH2) corresponds to the consequent development of disseminated intravascular coagulation (DIC) and consequent multiorgan failure;

  • Type 2 IM occurs due to an imbalance of myocardial oxygen demand (O2) due to septic hypoxemia and vasoconstriction;

  • Venous thromboembolism due to hypercoagulability, which, among other factors such as active inflammation, DIC, prolonged rest, oxidative stress, endothelial dysfunction, increased platelet activity, mechanical ventilation, liver dysfunction, central venous catheter, nutritional deficiency in such patients worsening of cardiac ischemia in patients with coronary heart disease (CAD) with an increase in D-dimer, fibrinogen, PE, deep vein thrombosis, and in-hospital mortality;

  • Acute myocarditis, directly caused by a virus that binds to ACE2 receptors of myocytes or indirectly through the cascade of immune response and cytokine release, causes myocardial degeneration and necrosis similar to STEMI;

  • Stress cardiomyopathy caused by infection with catecholamine induced by myocardial stunning or macro/microvascular spasm with Tako-tsubo syndrome.4,5,7

Heart Failure

All the mentioned pathophysiological mechanisms in patients with COVID-19 (increased need for O2, myocarditis, stress cardiomyopathy, ischemic infarction, cytokine syndrome, increased pulmonary pressure, and venous thromboembolism) lead to the development or worsening of existing HF with clinical signs of impaired ejection fraction (EF) of left ventricle.8

Survival of patients with HF and COVID-19 infection is significantly worse. This also applies to all forms of HF [left ventricular EF (LVEF), midrange EF, and reduced EF].9,10

Today, in the conditions of the COVID pandemic, it is recommended to use modern information technologies and telemedicine in monitoring patients with HF. Virtual visits can be organized with medical consultations, giving practical advice, measuring blood pressure, pulse, jugular pulse status, edema, determining electrolytes, international normalized ratio, and renal function, monitoring pulmonary arterial pressure, COVID-19 testing, with the assessment of necessary procedures (cardiac testing, echocardiography, ergometry, catheterization, and coronary angiography), the need for more intensive care, nutrition, phlebotomy, home medication, the need for intensive and palliative care, the installation of implantable cardioverter defibrillator and cardiac resynchronization therapy devices.8

Cardiac Arrest

Preliminary results of the COVID-19 and CVD WHF studies show a high percentage (38%) of sudden death, suggesting a number of causes that can cause cardiac arrest in COVID-19 patients. Acute myocarditis and Takotsubo cardiomyopathy, acute coronary syndrome (ACS), hypoxemia, high systemic inflammation, coagulation disorders (PE, coronary thrombosis, ND stroke), cardiac tamponade, tamponade, electrolyte imbalance, arrhythmogenesis (drugs inducted nondiagnostic canalopathies or direct effects of COVID-19) and genetic predisposition.3

ACS

The most dramatic event that can occur during COVID-19 infection is STEMI/NSTEMI, which has a specific clinical picture as in the case report that follows. In the first days of COVID-19, the infection most often affects the lung parenchyma with the rapid development of dyspnea, cough, and the appearance of specific infiltrates on the lungs seen as ground glass opacities on X-rays with the appearance of specific nodular changes that melt over the next 10 days and lead to pulmonary edema with the need for oxygen therapy and connection to a respirator (Figs 1A to C).11

Figs 1A to C: Chest X-ray images. Chest X-ray on: (A) day of admission, (B) day 6, (C) day 14 of hospitalization. Peribronchial ground glass opacities and nodular opacities in both lung fields were deteriorated7

Electrocardiogram changes are initially nonspecific at hospital admission, and already on the 14th day of stay, the newly formed ST elevation and T-wave inversion (Figs 2A and B)11 are registered, which indicates a coronary lesion, which indicates due to threatening cardiogenic shock coronarography with antiepidemic a measure to spread the infection and protect medical staff from infection (protective suits, masks, gloves, disinfection) which prolongs the intervention time significantly. During coronary angiography, the patient is diagnosed with multidirectional CAD (Figs 3A to C)11 and PCI intervention with drug-coated stent implantation in left anterior descending, right coronary artery (RCA), and left circumflex artery is performed, and successful reperfusion is achieved (Figs 4A to C). Further, the patient’s condition worsens with the development of cardiogenic shock and death.11

Figs 2A and B: Interval changes of ECG. ECG on: (A) day of admission and (B) day 14 of hospitalization. New onset ST-segment elevation in V1-V2 leads and T wave inversion in V3-V6 leads were observed. aVR, augmented vector right; aVL, augmented vector left; aVF, augmented vector foot; ECG, electrocardiogram7

Figs 3A to C: Baseline coronary angiogram. (A) Coronary angiogram showed severe stenosis in mid portion of left descending coronary artery, (B) proximal portion of left circumflex coronary artery, and (C) proximal portion of RCA. White arrows indicate coronary lesions in each vessel7

Figs 4A to C: Final coronary angiogram after PCI. (A) Drug eluting stents were implanted in mid portion of left descending coronary artery and (C) proximal portion of RCA. (B) Ballon angioplasty was done in proximal portion of left circumflex coronary artery7

Comparative studies were performed with meta-analysis of data showing that in all countries affected by COVID-19 infection, a significant prolongation of time from the onset of the first symptoms to the arrival of a doctor was registered, which differs in certain periods-COVID-19 waves.12,13

It was also noted that the hospital admission of patients with ACS and COVID-19 infection at the time of the “lockdown” was significantly lower. Explanations can be found in the workload of health workers during a pandemic with increased stress, anxiety, the priority of COVID patients, lockdown measures with isolation, loneliness, lifestyle modifications, increased depression, prolongation of ischemia, difficulty consulting a doctor with existing comorbid conditions such as are hypertension, diabetes, obesity, air pollution with dust particles-smoke, nitric dioxide, other pollutants, which with the use of cardiovascular therapy (angiotensin-converting enzyme (ACE) inhibitors, angiotensin II blockers, and drugs for COVID with their side effects, toxicity, interactions with cardiovascular drugs, etc.) with age and direct effects of SARS-CoV-2 on the body with inflammation and production of interleukin-6, prothrombotic effects with hypercoagulability, cardiac damage recorded by cardiac biomarkers (NT pro-BNP, troponin), immune response with cytokine response and unbalanced consumption/need for O2 leads to a poor outcome.4,12,13

The European Society of Cardiology (ESC) has included COVID-19 in its CVD Prevention Guidelines 2021 as a possible cause of CVD.

According to WHO records, Bosnia and Herzegovina are one of the countries with a high risk of cardiovascular mortality.14 Therefore, prevention and the fight to reduce risk factors for CVD is a priority, especially during the COVID-19 pandemic. The 2021 ESC Congress promoted that a 1-year dose of PCSK9 siRNA significantly reduced the lifetime risk for CV events,15 and influenza vaccination should be considered part of inpatient treatment after MI due to its beneficial effect on treatment outcomes and reduced mortality.16

Air Pollution and Climate Change in COVID-19

According to the reports of the ESC Congress in 2020, about 790,000 people die in Europe as a direct result of air pollution, of which ischemic heart disease accounts for 40%, stroke 8%, 32% for other noncommunicable diseases, while only 7% for pneumonia, 7% on lung cancers, and 6% on chronic obstructive pulmonary disease. A close link has been established between climate change, air pollution, and the covid pandemic and their detrimental effects on cardiovascular health. Decarbonization of the world with the abolition of fossil fuels in energy production and the transition to “healthy-green” sources through solar and wind power has become a goal of the UN and WHO, WHF, and ESC because it is also a fight for heart health. This was confirmed by the ESC Congress 2021. The effects of air pollution and SARS-CoV-2 infection can be triggers of acute cardiovascular events through the inflammatory response with increasing levels of CRP, fibrinogen, and cytokines with pronounced systemic inflammation and cytokine storm in COVID-19 infection. Then the autonomic nervous system is involved with a change in heart rate (higher/lower) due to pollution with COVID-19 myocardial damage with increased troponin, binding of COVID-19 to ACE2 receptors, antiviral drugs, corticosteroids, and others, with pollution-facilitated thrombosis/coagulability with inhibition of fibrinolytic capacity because the COVID-19 infection causes hypercoagulability with prothrombotic risk. Oxidative stress with myocyte telomere damage in pollution is presented in COVID-19 infection with higher body needs for O2, and the increase in cardiometabolic requirements due to systemic infection caused by respiratory weakness leads to pollution caused by vasoconstriction via endothelin with COVID-induced arrhythmia. Air pollution leads to the progression of atherosclerosis with increasing plaque vulnerability and the possibility of its rupture, which is emphasized by COVID-19. Decreased O2 saturation due to air pollution in COVID-19 potentiates endothelial dysfunction and oxidative stress that affect the clinical course of patients and their prognosis.4,17,18

Diagnostic Algorithm in COVID-19 caused by Acute Heart Damage

The ESC published the 2020 Guidelines to the diagnosis and treatment of patients with COVID-19 infection and CVD, in which it highlighted the most significant steps in the treatment of such patients. The algorithm is shown in Figure 5.4

Fig. 5: Algorithm for the diagnosis of COVID-induced acute myocardial injury optimizing the available imaging techniques. *hs-cTn > 99th percentile of its upper normal lipit, or >5 times the upper normal limit in COVID patients. ACS, acute coronary syndromes; AKI, acute kidney injury; BNP, brain natriuretic peptide; CMR, cardiac magnetic resonance; CT, cardiac tomography; DE, delayed enhancement; HF, heart failure; ICA, invasive coronary angiography; PCI, percutaneous coronary intervention4

In addition to cardiac biomarkers that indicate damage to the heart and blood vessels in COVID patients, the role of echocardiography is important.

In a Mostar study of 119 patients with COVID-19 infection and 96 patients without COVID, an echocardiographic assessment was performed, and LV dilatation, decreased EFLV, pseudoedema, focal changes, diffuse changes, elevated telediastolic pressure, mitral and tricuspid regurgitation, PE, thromboembolism in the heart, which indicates all the complexity of COVID infection and its systemic effects.19

Angiographic findings in STEMI patients before and during the COVID pandemic show statistically significant differences in time:

  • from symptoms onset to hospital admission (p < 0.001);

  • from hospital admission to reperfusion; (p = 0.001);

  • from symptoms onset to reperfusion (p < 0.001);

which is certainly caused by additional antiepidemic measures and protection of medical staff from infection.5,20

Clinical presentation and angiographic findings in STEMI patients before and during the COVID pandemic show a statistically significant increase in the degree of stenosis and multivessel CAD (p < 0.001). A larger number of patients with ventricular arrhythmias and congestive HF with an increase in in-hospital mortality.

Delay or failure to treat patients with ACS during a COVID pandemic causes:

  • Early complications such as sudden death due to cardiac arrest, acute HF, cardiac tamponade, cardiogenic shock, ventricular septal defect, acute functional mitral regurgitation, intravascular thrombosis, and acute pulmonary embolism (PE);

  • Late complications such as chronic HF, new abnormalities in LV motility, severe valvular heart disease, and pulmonary hypertension caused by right ventricular ischemia (RV), new STEMI, ventricular arrhythmias, and atrial fibrillation;

  • Organizational needs such as long-term intensive treatment with frequent mechanical ventilation, frequent and long-term examinations and an increase in indications for stress testing, an extension of the waiting list, and long-term waiting for examination.

All this requires better organization of transfers from home to the health institution, introduction of new diagnostic and treatment protocols, and compliance with antiepidemic measures to protect healthcare staff and patients with the use of modern technologies and telemedicine in monitoring patients.20

We can find that the number of hospitalizations during the COVID pandemic is significantly lower (−47%), and the number of deaths due to AMI is significantly higher (+12.5%), which shows a significant difference (p = 0.03) and this applies to both STEMI and for NSTEMI. Complications after AMI during the pandemic were also 11.3% higher (p = 0.02). Cardiac biomarkers during the COVID pandemic in AMI are higher, creatinine kinase-MB (p = 0.05), CK (p = 0.04), and NTproBNP (p = 0.03) with a decrease in EFLV (p = 0.01).5

In 2020, the American Society of Cardiology published recommendations as part of a strategy for the maximum safety of medical personnel and the appropriate use of personal protective equipment:

  • The US FDA has approved two on-site tests for COVID for rapid diagnosis, and the tests are widely available and routinely provided to all patients with STEMI in order to better diagnose and risk patients and optimize treatment plans and hospitalization. Laboratory and postcoronary treatment.

  • Appropriate protective equipment is needed by all health workers in emergency services, hospitals, emergency PCI departments, and the most critical floor laboratory team. A cap coat, gloves, full face mask, and N95 respirator mask are recommended for all floor laboratory staff during PCI and for all AMI patients during the COVID pandemic.

  • Primary PCI is the standard of care for patients with AMI who report within 90 minutes of the first medical contact.

  • This should be the standard for all STEMI patients during the COVID-19 pandemic, with a warning that depending on available staff and protective equipment and additional testing and determination of floor laboratory use with mandatory terminal cleaning after each procedure.

  • In the absence of these resources should be considered the first approach to fibrinolysis.

  • Additional time may be given to diagnose AMI with echocardiography to assess wall motility and COVID-19 status with potential respiratory-assisted treatment, further extending door-to-balloon time.

  • It is not recommended to transport the patient directly to the cat-laboratory due to logistical problems, time delay, and diagnosis of STEMI with COVID-19 infection, but it is recommended to go to the emergency room until complete diagnosis and treatment plan with consultation with an interventional cardiologist who then mobilizes the cardiology team. and a floor cat-laboratory for intervention.

  • It is emphasized that not all patients with COVID-19 and STEMI, with or without coronary occlusion, will benefit from any reperfusion strategy or mechanical support. Those with COVID-19 and severe pulmonary decompensation (acute respiratory distress-ARDS) or pneumonia and who have been intubated in the intensive care unit and who are considered to have excessive mortality are eligible for enhanced medical care.

  • Patients with NSTEMI and positive for COVID-19 should be treated with medication and taken for emergency coronary angiography and possible PCI only in case of high risk (GRACE score > 140) or in case of hemodynamic instability.

  • Adapt these recommendations individually to each PCI center in the health care system, STEMI referral hospitals, and emergency services, and to all cardiologists and emergency specialists in each hospital. The health system must recognize the competitive principles of timely reperfusion, safe regional transport, and treatment of potentially high-risk patients while emphasizing the protection and safety of all health personnel.21

VACCINATION

Vaccination against COVID-19, along with other antiepidemic measures, remains the only real preventive measure to prevent the occurrence and complications of damage to the heart and blood vessels. This is proven by the analysis of vaccinated and unvaccinated people and their mortality (Fig. 6).22

Fig. 6: Estimated U.S. seven-day rolling average of daily deaths with and without vaccination17

Therefore, a complete system of education, information, and work with patients and the population should be developed in order to get acquainted with the effects of human viruses, vaccination purposes, and the need to introduce not only two doses for successful vaccination but also booster doses to reduce the risk of reinfection and major disease consequences, and lowering mortality.

The entire population should be involved in the education program, as well as all health resources, medical and educational workers, the media, as well as patients who have survived the human disease, to promote vaccination as the only successful one in preventing the disease.23

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