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11 Articles in Volume 21, Issue #1
Advanced Practice Matters with Theresa & Jeremy: Mentorship
Ask the PharmD: What is a true opioid allergy?
Behavioral Medicine: How Clinicians Can Reduce the Stigma Attached to Chronic Pain
Chronic Headache: How to Conduct a Virtual Neurological Examination
COVID-19 Long Haulers: A Look at Cardiovascular Risk
How COVID Has Changed Pain Practice and Policies
How to Conduct a Pain Evaluation Using Telemedicine
Inside the Potential of Biologics for the Treatment of Rheumatoid Arthritis
Managing Pain in Parkinson’s Disease
Spinal Cord Stimulation Shown to Improve Pain and Movement in Parkinson’s Disease
TeleRheumatology Before and During the COVID-19 Pandemic

COVID-19 Long Haulers: A Look at Cardiovascular Risk

Cardiac diseases have been well documented in COVID-19 infections. Here, four cases demonstrate how long-range cardiac symptoms may emerge in patients with and without pre-existing CV disease even after COVID recovery.

COVID-19 infection may cause a number of clinically significant cardiovascular events in connection with what is being called Post-COVID Syndrome or Long COVID. An indirect effect is related to the delayed diagnosis of urgent non-COVID conditions, because of concern with going to a hospital. This has led to upticks in out-of-hospital heart attacks and strokes.1

This article will review the cardiovascular (CV) conditions directly attributed to the SAR-CoV-2 infection, including those related to hypercoagulability and acute cardiac injury, and explore potential long-range CV problems. A hypothetical COVID and/or COVID long hauler case leads each discussion. (See also, details on how to define long COVID).

COVID-19 infection may cause a number of clinically significant cardiovascular events in connection with what is being called Post COVID Syndrome or Long COVID. (Image: iStock)

 

 

#1: COVID-19 Infection and Deep Venous Thrombosis 

Case 1 Presentation: A 62-year-old female suddenly developed right calf pain and pleuritic left-sided chest pain. One week earlier she was seen in the ED for fever and a cough. At that time, her examination was unremarkable; a chest x-ray and laboratory tests were normal. A nasal swab was obtained, and she was told that she likely had COVID-19, to shelter-in-place at home but to return if her breathing became labored. Her COVID-19 test was positive.

Over the next week, the patient stayed in bed and her cough and fever gradually improved, but she felt persistently exhausted. Her past medical history is significant for obesity, hypertension, and type 2 diabetes. On follow-up examination, her lungs are clear, the cardiac examination is unremarkable, other than a resting tachycardia, and her right calf is tender.

What is the diagnosis and how would you proceed?

The most likely diagnosis is right extremity deep venous thrombosis (DVT) and possible pulmonary embolus. This patient should be immediately hospitalized and undergo both a lung scan and an extensive evaluation for potential pulmonary and cardiac abnormalities. She should be treated with full-dose anticoagulation.

Case 1 Discussion: Hypercoagulability and COVID-19

The rate of DVT in patients hospitalized with severe COVID-19 infection has ranged from 10% to 30% in most series.2 DVT most commonly occurs 4 to 10 days after hospitalization and about one-third of DVT cases are associated with pulmonary embolism.3 Clinical and/or laboratory evidence of hypercoagulability is associated with COVID-associated mortality. Laboratory tests include elevated D-dimer and fibrinogen levels, mild thrombocytopenia, and modest prolongations of prothrombin time (PT) or partial thromboplastin time (PTT). COVID-19 infection causes diffuse microangiopathy and widespread thrombosis, much more severe than other viral diseases, such as influenza.4

Thromboprophylaxis is being recommended for all hospitalized COVID-19 patients. Typical treatment involves daily low-molecular-weight heparins or twice-daily unfractionated heparin. Because there has been a high rate of thrombotic events despite thromboprophylaxis in critically ill patients, many investigators have recommended high doses of anticoagulants and extending the anticoagulation long after hospital discharge.

At the time of this writing (December 2020), the prevalence of DVT and/or pulmonary embolism in non-hospitalized patients is unknown. However, this Case 1 patient was at added risk of thrombotic events because of complete bed rest and her comorbid obesity and type 2 diabetes.

 

#2: Acute Cardiac Injury After COVID Recovery

Case 2 Presentation: A 40-year-old healthy, athletic male has recuperated from a moderate COVID-19 infection that began 3 weeks ago with fever, exhaustion, and a cough. He saw his primary care physician and a diagnostic test confirmed the clinical suspicion of COVID-19. He had a recurrent fever for the next 10 days and experienced loss of taste and smell but complained of only slight respiratory post-COVID symptoms. During the past week, he has gradually regained his strength and energy and went back to work a few days ago – after his follow-up COVID test was negative. An avid, long-distance runner who has completed three marathons, he began a 3-mile run and, after a few minutes, became very short of breath with dull, substernal chest pain.

How would you proceed?

Most likely, this man is simply attempting to exercise too quickly and needs to start much slower, beginning with short walks. Although there are no firm data on COVID recovery, many reports note that it takes weeks until people with even moderate infections are back to baseline.5 It is much less likely that his new post-COVID symptoms represent an acute coronary event, especially with his excellent health. However, COVID infection may cause acute cardiac injury and this patient should have an emergent cardiac evaluation. If the cardiac evaluation is unremarkable and he has no further cardiopulmonary symptoms, he can slowly resume exercise.

Current recommendations for resuming exercise after documented COVID infection in highly active people are:6

Asymptomatic COVID

  • no exercise for 2 weeks from positive test
  • close monitoring for symptoms
  • slow resumption of exercise

Mild Post-COVID symptoms, not hospitalized

  • rest for 2 weeks
  • medical professional evaluation, with consideration of echocardiogram, EKG, before returning to exercise

Hospitalized for severe COVID-19 infection

  • cardiac evaluation during hospitalization and 2 weeks after discharge
  • close monitoring and slow resumption of activity with close cardiac follow-up

Case 2 Discussion: Acute Cardiac Disease 

Approximately 20% of hospitalized COVID patients show evidence of acute cardiac disease, based primarily on biomarkers, such as elevated troponin, and/or cardiac imaging.7 In those patients, the elevation of cardiac biomarkers has correlated with disease severity and mortality. These COVID-related acute coronary events occur most often in patients with underlying coronary artery disease.

However, fulminant myocarditis and acute coronary syndrome have occurred in COVID-19 patients with no previous CCV disease, including in professional athletes. In most of these reports, the COVID-infection had been mild and the patients had not been hospitalized. Boston Red Sox pitcher Eduardo Rodriguez and Buffalo Bills tight end Tommy Sweeney, for example, have both been sidelined for the season after being diagnosed with COVID-related myocarditis.8 Four of 26 athletes from Ohio State University who had mild COVID-infections had cardiac MRI findings of myocarditis, although none of them were symptomatic.9

Although the finding of acute cardiac injury in 20% of patients with COVID infection is worrisome, it has not correlated with evidence of significant structural changes or a notable increase in cardiac diagnoses during hospitalization for severe COVID-infections. In a study out of the United Kingdom, three-quarters of hospitalized patients had elevated high-sensitivity troponin but even in those with abnormal cardiac MRIs, echocardiograms demonstrated normal systolic function and no regional wall motion abnormalities.10 An international patient registry of 3,000 hospitalized COVID-19 patients found that only 2% had congestive heart failure, 0.5% had acute coronary syndrome, and 0.1% had myocarditis.11

 

#3: Post-COVID Fatigue and Development of Cardiopulmonary Disease 

Case 3 Presentation. A 58-year-old previously healthy male had an episode of probable moderate COVID-19 infection in March 2020. He was febrile for 1 week and experienced myalgias and fatigue after COVID – for the next 3 weeks. At the time of his illness, there were no COVID tests available, but his PCP told him that he was quite certain that the patient had COVID-19. Gradually, he began to feel better but never regained his normal energy. His exercise tolerance continued to be poor, noting that he was short of breath after walking up one flight of stairs at home. His PCP ordered an EKG, a chest X-ray, and lung scan, all of which were normal.

How would you proceed?

Although many patients take weeks to return to normal following COVID-infection, this patient’s persistent shortness of breath are concerning for new cardiopulmonary disease. The normal chest X-ray and lung scan help exclude post-COVID lung disease and make a cardiac etiology more likely. This patient should undergo a comprehensive cardiac evaluation.

Case 3 Discussion: Chronic Cardiac Disease and COVID Infection

As discussed, evidence of acute cardiac injury is common during COVID-19 infection but the clinical significance of this is unclear. Most often the cardiac ejection fraction is normal during hospitalization for severe COVID infections, but echocardiographic studies have revealed right ventricle abnormalities and left ventricular diastolic dysfunction.12 These abnormalities and dysfunction are characteristic of heart failure with preserved ejection fraction. It has been postulated that viral-induced inflammation with subsequent hypoxemia and acute respiratory distress syndrome (ARDS) causes cardiac remodeling with right ventricular dilatation, pulmonary hypertension, and left ventricular diastolic dysfunction (see Figure 1).12

 

There has also been an increase in stress cardiomyopathy (also known as Takotsubo syndrome), with a four-fold rise from pre-pandemic levels in one report.13 It is too early to know whether COVID-19 infection will eventually lead to chronic cardiac disease, but Marc Pfeffer, MD, a cardiologist at Brigham and Women’s Hospital in Boston, has expressed worry, stating: “We knew that this virus, SARS-CoV-2, doesn’t spare the heart. We’re going to get a lot of people through the acute phase but I think there’s going to be a long-term price to pay.”14

In an autopsy series, patients who died of COVID often had viral fragments in cardiac tissue with inflammatory changes.15 One researcher cautioned, “We see signs of viral replication in those that are heavily infected. We don’t know the long-term consequences of the changes in gene expression yet. I know from other diseases that it’s obviously not good to have that increased level of inflammation. The question now is how long these changes persist. Are these going to become chronic effects upon the heart or are these −we hope − temporary effects on cardiac function that will gradually improve over time?”16

 

#4: Post-COVID Syndrome and COVID Long Haulers

Case 4 Presentation: A 35-year-old nurse was diagnosed with COVID-19 infection while working in an ICU. Her post-COVID symptoms were mild, and she was febrile for only a few days and thought that she had recovered fully. However, after returning to work 3 weeks later, she developed persistent headaches, nausea, diarrhea, and exhaustion. Intermittently, she has been short of breath and described that “my heart is racing out of control.” Her symptoms have persisted for the past 2 months and she has been unable to return to work. A repeat COVID test was negative, and her physical examination, as well as routine laboratory tests and a chest X-ray, were normal.

How would you proceed?
The multiple symptoms experienced by this patient 3 months after COVID-19 infection with normal laboratory tests and an unremarkable physical examination are suggestive of Post-COVID Syndrome or Long COVID. However, as noted in patient Cases 2 and 3, some young, healthy people with mild or moderate COVID infections may develop chronic cardiac disease. Therefore, this patient should undergo a comprehensive cardiac and pulmonary evaluation. If that is unremarkable, she should be referred to a multidisciplinary rehabilitation unit.

Case 4 Discussion: Post-COVID Syndrome Treatment

At least one-third of adults with mild COVID not requiring hospitalization have not returned to their normal health two to three weeks after positive testing.5   This patient population includes young, healthy adults. Another 13% are still symptomatic after 1 month, 5% at 2 months, and 2% at 3 months. These patients have been grouped together under the rubric of long COVID or COVID long haulers.17

Post-COVID Syndrome has been more common in females and older patients and in patients who had multiple post-COVID symptoms initially. COVID fatigue has been present in 98% and headache in 91% of COVID long haulers. Other than the universal symptoms of COVID fatigue and headaches, the other symptoms have largely clustered as either respiratory or multisystem, with multisystem including the GI, cardiac with palpitations or tachycardia, and neurologic systems (both cognitive and psychiatric).

Post-COVID Syndrome has many similarities to other post-viral syndromes including chronic fatigue syndrome (CFS) and fibromyalgia, as recently acknowledged by Anthony Fauci, MD.18

A number of physicians with long COVID have written about the uncertainty and lack of objective data to validate their own multiple symptoms, as described by Jeffrey Siegelman, MD, an emergency medicine doctor in Atlanta, “Now, after more than 3 months of living with coronavirus disease and the fatigue that has kept me couch-bound, I have had ample time to reflect on what it means to be a patient … the next time I care for someone with vague abdominal pain, or fatigue, or paresthesia, or any of the myriad conditions that are uncomfortable on the inside but look fine on the outside, I will remember that these symptoms are real and impactful for patients.”19

Medical centers across the US and the UK have established Long COVID centers to better evaluate and treat this perplexing condition.

 

Practical Takeaways

In the early stages of the COVID-19 pandemic, there was a dramatic increase in heart attacks and strokes happening in the community as a result of the public’s fear of visiting medical facilities. Even at this stage of a third wave, there still are many patients who are not keeping up with their routine healthcare and may ignore cardiopulmonary post-COVID symptoms. It also has become clear that pre-existing cardiovascular disease is a major risk factor for COVID-19 related disease severity and mortality. Hypercoagulability has been present in 10% to 30% of hospitalized patients leading to thromboprophylaxis as the standard of care in any patient with severe COVID-19 infection.

As the pandemic has gone on, there is also evidence that individuals with no pre-existing CV disease often have evidence of acute cardiac injury during COVID-19 infection. This may occur in healthy, athletic individuals who had mild or moderate infections. Whether this will result in chronic, cardiovascular disease has yet to be determined. There also must be careful follow-up over the ensuing months in patients with multiple, unrelated symptoms.

Last updated on: January 26, 2021
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