COVID-19 and the Implications of Deferred Cardiovascular Care

RELEASE DATE

February 1, 2022

EXPIRATION DATE

February 29, 2024

FACULTY

Amy Wu, PharmD
Ambulatory Care Pharmacist
Sterling, Virginia

FACULTY DISCLOSURE STATEMENTS

Dr. Wu has no conflicts of interest in relation to this activity.

Postgraduate Healthcare Education, LLC does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.

ACCREDITATION STATEMENT

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Postgraduate Healthcare Education, LLC is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

UAN: 0430-0000-22-019-H01-P
Credits: 2.0 hours (0.20 ceu)
Type of Activity: Knowledge

TARGET AUDIENCE

This accredited activity is targeted to pharmacists. Estimated time to complete this activity is 120 minutes.

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DISCLAIMER

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

GOAL

To provide pharmacists with an overview of the cardiovascular manifestations resulting from coronavirus disease 2019 (COVID-19) infection, impact on public health, and opportunities for pharmacists’ involvement in patient education and assistance in cardiovascular disease management.

OBJECTIVES

After completing this activity, the participant should be able to:

  1. Describe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19.
  2. Identify the cardiovascular manifestations due to COVID-19.
  3. Summarize the cardiovascular sequelae of COVID-19.
  4. Review the pharmacist’s role and potential interventions to educate and assist patients in cardiovascular disease management.

ABSTRACT: Acute cardiovascular impairment caused by SARS-CoV-2 infection manifests in a variety of ways, including acute myocardial injury, stroke, arrhythmias, venous thromboembolism, pulmonary embolism, and acute coronary syndromes. The COVID-19 pandemic has caused patients to fear adhering to preventive cardiovascular care and seeking immediate care for critically illness, thereby delaying cardiovascular disease care. Pharmacists can help to discuss cardiovascular care maintenance and health preservation for those at high risk of cardiovascular disease. Additionally, pharmacists can provide medication counseling, engage in remote patient monitoring with the patient and healthcare provider, and recommend lifestyle modifications, such as physical activities, nutrition, and vaccines.

SARS-CoV-2, a novel coronavirus, was first reported in Wuhan, province Hubei, China, in December 2019. This is the third reported animal-to-human coronavirus transmission in the past 2 decades, all of which have resulted in a worldwide pandemic.1 The three coronaviruses that have resulted in disease outbreaks include the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002, the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, and the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus belongs to the family Coronaviridae and derives its name from the word “corona,” which is the Latin word for crown. Under an electron microscope the appearance of the virus presents as unique spherical particles with a rim of projections that resembles the solar corona. The size of the virus was found to be 60 nm to 140 nm in diameter, with characteristic spikes of 9 nm to 12 nm, which is similar to the Coronaviridae family. The novel coronavirus was discovered to be phylo-genetically more similar to two bat-derived coronavirus strains (88% similarity) than coronaviruses that infect people, such as SARS-CoV (79% similarity) and MERS-CoV (50% similarity).2

Coronaviruses are single-stranded, enclosed, positive-sense RNA viruses that were originally discovered in humans in 1965. On February 11, 2020, the Coronaviridae study group of the International Committee on Taxonomy of Viruses called the virus SARS-CoV-2 based on phylogeny and taxonomy. As a result, the World Health Organization named it the coronavirus disease (COVID-19), and on March 11, 2020, it declared COVID-19 as a pandemic due to the global spread.2

Viral infections have a direct impact on the cardiovascular system, according to clinical observations of disease patterns. They can cause inflammation to the heart, leading to injury to the cardiovascular system. Scientists from the CDC Response Team found that patients who had COVID-19 had a 16-fold increased chance of having the inflammatory diseases myocarditis and pericarditis. Individuals are more prone to a poor prognosis if they present with cardiovascular and metabolic comorbidities.

CLINICAL PRESENTATION

Transmission of the coronavirus from human to human is similar to other respiratory viruses that can be spread through respiratory deposits from sneezing, coughing, breathing, or talking with close contacts. In most cases, the incubation period is between 3 and 5 days, with an interval range from 2 days to 2 weeks. From 4 to 7 days, symptomatic patients can experience fever, malaise, nasal congestion, dyspnea, and cough. Anosmia, sore throat, muscle weakness, weariness, headache, and diarrhea are further clinical manifestations. From Day 5 to the second or third week, viral pneumonia develops with ground glass appearance of the lungs, alveolar exudates, interlobular involvement, and bilateral patchy consolidation accompanied by hypoxemia, depending on clinical progression. Due to the evolving variants of the virus, the clinical presentation also continues to evolve.

Severe acute respiratory syndrome, multiorgan failure, and death can occur in instances where the patient continues to worsen. The cytokine storm, in which an unscaled and disproportionately strong immune response suddenly emerges in response to an external stimulus such as COVID-19, has a particularly dangerous clinical course with high mortality. Laboratory tests may reveal leukopenia, thrombocytopenia, lymphocytopenia, increased C-reactive protein levels, D-dimers, liver enzymes, or signs of myocardial lesion.3

ROLE OF ANGIOTENSIN-CONVERTING ENZYME 2 AND SARS-COV-2

The membrane-bound aminopeptidase angiotensin-converting enzyme 2 (ACE2) plays a critical function in the cardiovascular and immunological systems. ACE2 is involved in cardiac function, hypertension, and diabetes mellitus development.4 ACE2 is a renin-angiotensin-aldosterone system (RAAS) counter-regulatory enzyme that degrades angiotensin II to angiotensin-(1-7), reducing its effects on vasoconstriction, fibrosis, sodium retention, and fibrosis.5 It has been found that ACE2 is a functional receptor for both SARS-CoV and SARS-CoV-2. The virus’ spike protein binds to ACE2, which is abundantly expressed in the heart and lungs, causing SARS-CoV-2 infection. SARS-CoV-2 mostly infects alveolar epithelial cells and causes respiratory symptoms. These symptoms are more severe in patients with cardiovascular disease, which can be linked to higher ACE2 secretion in these patients compared with healthy people.

The use of RAAS inhibitors can elevate ACE2 levels. Given that ACE2 is a functional receptor for SARS-CoV-2, antihypertensive medication with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) should be carefully examined in patients with COVID-19. It is controversial whether patients who are taking ACEIs or ARBs should switch to a different antihypertensive medication.4

In Northern Italy, the study of a large population with cardiovascular disease did not find that the use of ACEIs and ARBs contributed to the risk of COVID-19.5 Similarly, Reynolds et al did not discover any significant connection between five frequently used antihypertensive medication classes and the risk of a positive COVID-19 test or severe COVID-19 presentations. Those antihypertensive drug classes include ACEIs, ARBs, calcium channel blockers, beta-blockers, and thiazide diuretics. This provides support that discontinuing ACEIs and ARBs could actually lead to an increase in mortality due to an exacerbation of cardiovascular and renal dysfunction.6

CARDIOVASCULAR MANIFESTATIONS OF COVID-19

Although respiratory symptoms are the most common COVID-19 symptoms, some patients experience severe cardiovascular damage. Furthermore, some patients with underlying cardiovascular diseases may be at a higher risk of dying. Understanding the damage caused by SARS-CoV-2 to the cardiovascular system, as well as the underlying mechanisms, is critical for quick and successful treatment of these patients as well as a reduction in mortality.4

Myocardial Injury

An elevated troponin level indicates myocardial injury, which can be caused by myocardial ischemia or nonischemic myocardial injury, such as myocarditis. One potential mechanism of SARS-CoV-2 infection–induced acute myocardial injury is its affinity for ACE2, which is extensively expressed in the heart and can cause direct myocardial damage.

A cytokine storm induced by anemia, an unbalanced response by type 1 and type 2 T-helper cells, sympathetic hyperactivity, and hypoxemic myocardial cell injury caused by respiratory failure are some of the other possible routes.7

In China, it is estimated that myocardial injury is prevalent in 7% to 20% of those hospitalized with COVID-19. Five of the very first 41 COVID-19 patients in Wuhan had elevated cardiac troponin I levels >28 pg/mL. Eighty percent of the patients with myocardial injury were hospitalized in the ICU. This suggests serious clinical implications of myocardial injury due to COVID-19.8

Heart Failure

New onset of heart failure was seen in up to a quarter of COVID-19 patients admitted and as many as one-third of those admitted to the ICU at Wuhan Jin Yin-tan Hospital between late December 2019 and January 26, 2020, even without a previous history of heart failure. This can be the direct result of systemic inflammation on the heart caused by the virus.9 Heart failure in COVID-19 could be due to a worsening of existing cardiovascular illness or the emergence of cardiomyopathy related to myocarditis or stress cardiomyopathy. In the setting of severe acute respiratory distress syndrome (ARDS) or pulmonary embolism (PE), isolated right-heart failure can be seen in the presence of pulmonary hypertension. Elevation of B-type natriuretic peptides is linked to a poor prognosis in individuals with ARDS.7

Left-ventricular hypertrophy and diastolic dysfunction are common in elderly persons with cardiovascular disease. As a result, when these patients are given large amounts of IV fluids to maintain blood pressure or as a vehicle for parenteral drug infusion, they may develop pulmonary edema. However, pulmonary edema seen in the presence of COVID-19 could be a symptom of pulmonary vascular damage caused by an excess of local ACE2. The increase in ACE2 causes significant vasoconstriction and microvascular dysfunction, as well as initiating the inflammatory process.7

Stroke

The majority of COVID-19 patients who have acute ischemic stroke have previous cardiovascular risk factors, large vessel atherosclerosis, small vessel disease, and cardioembolism—similar to acute ischemic stroke patients without COVID-19. In one report, five young patients who presented with major intracranial vessel occlusion had severe strokes during acute COVID-19 disease. One of the patients had a previous stroke, and three had atherosclerotic risk factors. Three patients had elevated D-dimer levels. This points to a complicated link between common risk factors, infection, and stroke, raising concerns about relatively younger individuals suffering a stroke during the ongoing pandemic. Nonetheless, the cause-and-effect relationship between COVID-19 and stroke is still not clear.10

Venous Thromboembolism and Pulmonary Embolism

In patients with COVID-19, a variety of studies have found varied rates of venous thromboembolism (VTE). VTE is more commonly seen in ICU patients and in cases of serious illness in general. Several case series and studies have established the value of various biomarkers, such as D-dimer, for individuals with COVID-19 who are at risk of developing VTE. D-dimer levels rise in COVID-19 patients, and they are also linked to a poor prognosis. D-Dimer levels more than 1 ug/mL on admission were found to be an independent risk factor for in-hospital death in a study involving 191 patients from China. However, there is no information about the anticoagulant therapy dose given to the participants in this study. D-dimer levels are known to be elevated in a variety of situations, including sepsis, immobility, and infection. As a result, a raised D-dimer level in COVID-19 patients is not recommended as a diagnostic bio-marker for VTE.11

When patients with COVID-19 developed a PE, the exact timing is unknown. The question is whether the condition manifests during the initial phase or during the follow-up period. It appears that patients were found to have been diagnosed with PE at the time of admission, during hospitalization, and after release.11

Arrhythmias and Atrial Fibrillation

In earlier reports of COVID-19 patients in Wuhan, it was noted that cardiac arrhythmias were the most common complication in 138 COVID-19 hospitalized patients (19.6%), and they were more common in those who needed ICU hospitalization.12

Arrhythmias may be caused by any one of the following mechanisms in the presence of COVID-19: 1) direct viral damage to myocardial cells and/or the conduction system; 2) worsening of pre-existing myocardial conditions or conduction disturbances; 3) adrenergic stress leading to electrical instability; 4) electrolytic derangements; or 5) acute coronary syndrome with ongoing ischemia. COVID-19’s high-grade systemic inflammatory state is another potentially relevant proarrhythmic component that should not be overlooked. According to Guo et al, in 187 COVID-19–positive patients, they found that malignant ventricular arrhythmias were twice as frequent in the presence of elevated troponin levels, 11.5% versus 5.2%. Ventricular arrhythmias could be the first clinical manifestation of SARS-CoV-2 infection.13

There is no direct evidence of a link between COVID-19 and new-onset atrial fibrillation (AFib). Multiple causes, such as hypoxia and catecholamine overload, can result in occurrences of AFib in patients who have a predisposition to AFib, as with any severe illness. Some COVID-19 patients develop myocarditis, which can lead to AFib. AFib patients taking antiarrhythmic agents, such as dofetilide, sotalol, amiodarone, and dronedarone, need careful monitoring of the QT inter val. It is recommended that discontinuing antiarrhythmic medications is reasonable if there is significant QT prolongation and COVID treatment is warranted.14

Acute Coronary Syndromes

The potential underlying mechanisms of acute coronary syndrome (ACS) in COVID-19 may be multiple and, to date, are not fully understood. Direct viral cellular damage, systemic inflammatory response with cytokine-mediated injury, microvascular thrombosis, endothelial dysfunction, and oxygen supply/demand imbalance leading to severe hypoxia have all been proposed as possible pathways contributing to the development of ACS. The immune and inflammatory responses play a strong role in the pathogenesis of atherosclerosis. By activating platelets and driving endothelial dysfunction, inflammation during viral infection can disrupt normal homeostasis and create a prothrombotic condition. Infections can also enhance sympathetic activity, resulting in coronary artery vasoconstriction. All of these biological and mechanical factors can cause atheromatous plaque erosion or rupture, which can lead to coronary thrombosis and ACS.15

IMPLICATIONS OF DEFERRED CARDIOVASCULAR DISEASE MANAGEMENT DUE TO COVID-19

Due to the pandemic, patients with cardiovascular concerns have delayed seeking preventive and acute care. Many patients delayed receiving care for cardiovascular conditions due to concerns of being infected by COVID-19. At the start of the pandemic, hospital emergency rooms saw a sharp decline in cardiovascular patients. Many patients skipped “nonessential” appointments and procedures in the early weeks of the pandemic as healthcare providers followed state and national guidelines aimed at pre-serving personal protective equipment, expanding ICU capacity, and protecting workers and patients from contracting the virus.16

Routine maintenance and preventive cardiology visits can be scheduled virtually through a telephone consult or a virtual visit to minimize COVID-19 exposure to both healthcare providers and patients. Virtual visits are preferred rather than avoiding or delaying care. Additional targeted virtual visits to those most vulnerable and at highest cardiovascular disease risk can be made using the health system’s information technology infrastructure. Preventive cardiology services are an excellent fit for telehealth since visits are less focused on in-office testing and a thorough physical examination and more on counseling. Increased visit frequency is required for lifestyle modifications, which can be supported by shorter, more frequent telemedicine encounters. Patients should be advised at each visit to report any new or troubling cardiac symptoms to their healthcare provider as soon as possible and not to delay getting treatment for any severe symptoms due to concerns about COVID-19.17

Several strategies can be employed to help ensure patients have access to their medications during the pandemic. The FDA is closely monitoring drug supply chain issues. Barriers to appropriate purchase of these medications, including time-consuming prior authorization processes, are recommended to be removed during this emergency. While certain higher tier medications may not be considered necessary medications, they can be lifesaving for people with the highest cardiovascular risk.17

REMDESIVIR

Remdesivir is FDA approved for use to treat COVID-19 in hospitalized patients. The effect of remdesivir on the QT interval is unknown since drug interactions have not been studied in clinical trials. However, per the manufacturer’s prescribing information, coadministration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended due to an antagonistic effect of chloroquine based on cell culture data demonstrating an antagonistic effect of chloroquine on the intracellular metabolic activation and antiviral activity of remdesivir.18

THE PHARMACIST’S ROLE

Pharmacists see patients much more frequently than other healthcare providers since they are easily accessible in the community setting. Many patients deferred appointments and procedures in the early weeks of the pandemic as healthcare providers followed state and national guidelines aimed at preserving personal protective equipment, expanding the ICU capacity, and protecting workers and patients from contracting the virus.

Remote patient monitoring is a method of collecting patients’ physiologic data outside of the traditional healthcare clinic setting. The data that can be collected include blood pressure, weight, blood sugar, heart rhythm, and heart rate. Clinically relevant data can be sent to the clinician, and patients can be monitored remotely by using a variety of wired and wireless devices. Being able to monitor patients remotely with the objective information can help providers to better manage patients more conveniently during the COVID-19 pandemic. For example, pharmacists can help patients by ensuring they are using their blood pressure monitor correctly and recommend using an upper-arm cuff versus the wrist or finger monitors. Patients need to be given the empowerment to actively engage in their care.17

Pharmacists can help to maximize the chances of successful smoking cessation, and a mix of counseling and pharmacotherapy is recommended. Techniques for regulating and reevaluating emotions during stressful periods may aid in the reduction of smoking impulses. Pharmacists can also counsel and encourage a lifestyle of healthy eating. For example, counsel patients to choose low-sodium and low-fat food choices for cardiovascular protection. It is essential to overemphasize the importance of other healthier coping mechanisms for stress management, such as meditation and exercise, in addition to stress eating.

CONCLUSION

Acute cardiovascular impairment caused by SARS-CoV-2 infection manifests in a variety of ways including acute myocardial injury, stroke, arrhythmias, VTE, PE, and ACS. The COVID-19 pandemic has resulted in deferred preventive and acute cardiovascular care. Pharmacists play a crucial role in educating the public about the importance of adhering to medical appointments for follow up visits, self-advocating their own health through remote patient monitoring programs, or recommending immediate medical attention for emergency or life-threatening cardiovascular situations such as a myocardial infarction or stroke when necessary. They can also emphasize the importance of lifestyle changes for better cardiovascular outcomes. Pharmacists can also educate patients about the importance of obtaining the vaccine to prevent the transmission of COVID-19. Community pharmacists are in a unique position where accessibility for the public is easier compared with other healthcare professionals, and they should provide as much guidance and counseling as feasible.

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