BEST PRACTICES :: CARDIAC BIOMARKERS
could explain why d-dimer is higher in COVID pneumonia than other historically seen forms of pneumonia.7
Similar to
the findings reported for cardiac troponin, in patients with COVID-19 the D-dimer values increase progressively in non- survivors whereas values remain around the upper limits of normal in survivors
In hospitalized patients with COVID, monitoring of co- agulation parameters can aid to predict deterioration and potentially to guide therapeutic measures including the in- tensity of anticoagulation. Pharmacologic prophylaxis of venous thromboembolism (VTE) is recommended for all hospitalized patients with COVID (Kim). If VTE is suspected and detected, the patient’s anticoagulation should advance from prophylactic to therapeutic dosing. In summary, d-dimer testing sheds light on important pathophysiological aspects of COVID-19 disease as well as contributes to more effective early risk assessment, on guidance on intensity of anticoagulation.
Cardiovascular issues in long-COVID Post-acute sequelae of SARS-CoV-2 infection (PASC) colloqui- ally understood as “long-COVD” is currently defined by the U.S. CDC as “Broad range of symptoms (physical and mental) that develop during or after COVID-19, continue for ≥2 months (i.e., three months from the onset), and are not explained by an alternative diagnosis.”8
Cardiovascular complaints are common
in long-COVID patients. Chest discomfort/pain is frequent and appears to resolve slowly. Chest discomfort persists in 12 to 22 percent of patients approximately two to three months after acute COVID-19 infection. There are a large number of diagnostic and therapeutic modalities being investigated in cardiovascular long-COVID.9
Suspected myocarditis and/or
an unexplained troponin uncovered in a patient’s evaluation should lead to a cardiac MRI. In persistently dyspneic patients, natriuretic peptides should be part of the initial workup to investigate for superimposed heart failure on top of any pul- monary disease. Hypercoagulability states typically manifest during acute-COVID and not long-COVID. However, monitoring for persistent, refractory, or recurrent disease should be done when clinically indicated and this evaluation is usually initiated with a d-dimer. We are also seeing a significant number of patients who are not suffering directly from COVID but have developed car- diovascular issues due to delaying care during the COVID-19 pandemic. Fear of being exposed to COVID-19 in healthcare settings has kept many patients from seeking care in Emergency Departments for potentially life-threatening issues. Also, many routine primary care and specialty care clinic visits have un- fortunately been cancelled, postponed, or converted to video visits where important physical exam findings may not get properly discovered. One example of a direct risk would be a patient moving into a more severe stage of heart failure due to delayed diagnosis. Indirect risks are patients that have increased risk factors of COVID-19 complications such as advanced age, coronary heart disease, high blood pressure, stroke survivors, congenital heart defects, and compromised immune systems not getting the care they need in a timely manner. Cardiovascular experts from across the globe have weighed in on the delays to care and the backlog of potentially life-saving interventions and procedures, with a concerning impact on health for many members of society.4 While the detailed epidemiologic future of the COVID-19
pandemic remains unfinalized at this writing, this fearsome disease has changed many features of acute cardiovascular
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care. This has included important new understanding of pathological mechanisms, diagnostics, and therapeutics. For- tunately, a number of excellent cardiopulmonary biomarkers had been developed pre-pandemic; and their performance characteristics have been readily deployed by clinicians and researchers to optimize the identification and risk stratifi- cation of the more vulnerable subsets of COVID patients. Many have critiqued our preparedness and our tools used in the course of this pandemic. I would argue that laboratory medicine was better poised to handle the challenges of this pandemic than at any time in the last century. For instance, it is sobering to consider that, if this pandemic had occurred 30 years ago, many of the biomarkers and nucleic acid tests effectively deployed in our current arsenal, including the tests discussed in this article, would not have existed. An unprecedented amount of inflammation and thrombosis accompany this particular viral disease, which may account for much of its ferocious nature. Cardiac troponin, natriuretic peptides and d-dimer testing are three highly useful tools for the clinician to discern the extent of these pathologic processes and intervene as early as possible during the patient’s presentation. A “second punch” from COVID has come with the unusual features and complications of disease convalescence that we see in the group of patients suffer- ing from long-COVID. Finally, access-to-care issues during the recent broad societal shutdowns have created a perfect storm of patients with brewing, advancing cardiovascular conditions for whom more rapid assessment and diagnostic evaluation will be essential in addressing these delayed, unad- dressed health issues. Fortunately, there is a solid collection of cardiovascular tools already readily available to initiate the investigation and develop personalized treatment plans.
REFERENCES:
1. Kaufman HW, Meyer III WA. The long-term health consequences of COVID- 19. Medical Laboratory Observer. 2022;54(3):8-16.
2. Giacca, M., Shah, A.M. The pathological maelstrom of COVID-19 and car- diovascular disease. Nat Cardiovasc Res (2022) 1, 200–210.
doi.org/10.1038/ s44161-022-00029-5.
3. Bozkurt, B., Kamat, I., Hotez, PJ. (2021). Myocarditis with COVID-19 mRNA vaccines. Circulation, 2021 144(6), 471-484. doi: 10.1161/circulationaha.121.056135.
4. Nicholls, M., The ongoing impact of COVID-19 on cardiovascular care. Euro- pean Heart Journal (2021) 00, 1–3. doi: 10.1093/eurheartj/ehab244.
5. Kim, AY, Gandhi, RJ In: Post TW, ed. UpToDate. UpToDate; 2022. Accessed March 22,2022.
https://www.uptodate.com/contents/ covid-19-management-in-hospitalized-adults
6. Mueller, C., Giannitsis, E., Jaffe, A.S. et al. Cardiovascular biomarkers in patients with COVID-19. European Heart Journal Acute Cardiovascular Care, 2021 10(3), pp.310-319. doi: 10.1093/ehjacc/zuab009.
7. Chen AT, Wang CY, Zhu WL et al. Coagulation Disorders and Thrombosis in COVID-19 Patients and a Possible Mechanism Involving Endothelial Cells: A Review. Aging and Disease. 2022 Feb;13(1):144. doi: 10.14336/AD.2021.0704.
8. Mikkelson ME, Abramoff B In: Post TW, ed. UpToDate. UpToDate; 2022. Accessed March 22,2022
https://www.uptodate.com/contents/ covid-19-evaluation-and-management-of-adults-following-acute-viral-illness
9. Raman B, Bluemke DA, Lüscher TF, et al. Long COVID: post-acute sequelae of COVID-19 with a cardiovascular focus. European heart journal. 2022 Mar 14;43(11):1157-72. doi: 10.1093/eurheartj/ehac031.
Sean-Xavier Neath, M.D., Ph.D., Associate Physician, Emergency Medical Services Medical Affairs and Clinical Development University of California, San Diego
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