New information regarding COVID-19 continues to emerge daily. This content was based on the sources available at the time of writing.
By Dr. Payal Kohli, MD, FACC
Cardiovascular disease (CVD) has been the number one killer of men and women in the United States and worldwide for decades—our biggest foe by far! However, more recently, heart disease has had an evil sidekick: COVID-19. Even though it's a respiratory virus, the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2) virus (which causes the COVID-19 illness) has cardiovascular implications for those with preexisting heart disease and associated co-morbidities, as well as possible implications for patients who may develop heart disease in the future as a result of vascular and myocardial inflammation.
These two most formidable nemeses, heart disease and COVID-19, teamed up to directly and indirectly increase heart disease morbidity and mortality, a phenomenon whose impact will play out over the next several years to decades. Some experts are calling this the "prevention" curve of the pandemic which will manifest itself through neglected chronic conditions and possibly direct vascular and metabolic effects of COVID-19 on survivors.1
Since the discovery of this virus in late 2019, the SARS-CoV-2 virus (COVID-19) has caused confirmed infections in more than 410 million people and is responsible for an estimated 5,812,463 deaths worldwide as of February 12, 2022, resulting in a 1.42% mortality rate overall.2 However, the mortality in patients with CVD is estimated to be much higher, highlighting the central role of the cardiovascular system in COVID-19-related mortality.
Although estimates are variable, studies suggest mortality in 10.5% of patients with CVD, with rates going as high as 52% in those with certain types of cardiac conditions, such as heart failure.3 Not surprisingly, the concomitant presence of elevated troponin in patients infected with SARS-CoV 2, which suggests direct or indirect myocardial injury, occurred more frequently in those with CVD and conferred a worse prognosis and higher risk of death.
Elevations of cardiac enzymes afforded a significantly worse prognosis, even in those without preexisting heart disease, suggesting that the mechanisms of cardiac damage are critical to the pathogenesis of the disease and its adverse consequences. In one study, the mortality rate in patients without CVD and normal troponin was 7.6%, with an increase to 13.3% for those with CVD and normal troponin. Troponin elevation in the absence of CVD raised mortality to 37.5%, with a mortality rate of 69.4% among patients with CVD and troponin elevation.3
Mechanisms of Cardiac Damage
In its early phase, which is the viral replication phase, COVID-19 viral loads increase exponentially, causing direct organ damage through infection of cardiac myocytes and endothelial cells, both of which express the ACE2 receptor, which the virus uses to gain entry into host cells. Although direct viral myocarditis can occur, it's thought to take place in fewer cases and not be the primary mechanism of troponin excursion.
As the immune response progresses to phase 2 with severe systemic inflammation, multiple other mechanisms of cardiac injury are activated, primarily a cytokine storm with release of IL-2, IL-10, IL-6, IL-8, and TNF-alpha, as well as a supply-demand mismatch from increased cardiometabolic demand in the setting of possible ongoing hypoxia, which can be a result of severe pneumonia or acute respiratory distress syndrome (ARDS).4 Endothelial activation can lead to thrombotic phenomenon and the possibility of coronary plaque rupture from the systemic inflammation and catecholamine surge, causing an acute coronary syndrome. Additionally, research published in the Journal of the American College of Cardiology shows that as many as 16.7% of patients develop abnormal arrhythmias as a result of infection. These complications roughly equal those associated with other coronaviruses, such as SARS and Middle East respiratory syndrome (MERS).5
Interplay of Comorbid Conditions
The presence of comorbid conditions such as diabetes, obesity, or hypertension are associated with significantly worse COVID-19-related prognosis, possibly through modification of the immune response, exacerbating the degree of viral replication, and immune bystander damage, as well as other mechanisms.
Diabetes
A large-scale French study revealed a case fatality rate of 10.6% in patients with diabetes who were hospitalized for COVID-19 during March 2020.6 Interestingly, in a multivariate model, only body mass index (BMI), and not long-term glycemic control (as reflected by the HBA1c and diabetic medication use), age, or type of diabetes (Type 1 or Type 2), appeared to predict risk of tracheal intubation and/or death within seven days.
Obesity
Studies have found that obese patients who became infected with SARS-CoV2 were 113% more likely to get hospitalized and 48% more likely to die compared to patients with a healthy weight.7 Given that many Americans are either overweight or obese, the impact of this is profound. Mechanisms of this increased risk are multiple: mechanical challenges due to pannus (increased abdominal adiposity makes ventilation more challenging), increased thrombophilia, compromised immunity and function of immune cells, and adverse inflammatory pathways being activated, among others.
Hypertension
Similarly, hypertension, which has both direct and indirect effects on the endothelium, was significantly associated with higher severity and mortality from COVID-19, with adjusted OR of severe illness being 2.4-2.9X higher and the adjusted HR for mortality being twice as high as those without hypertension, after accounting for age, sex, location, demographic factors, and comorbidities.8 The mechanisms of these effects are under study, but increased expression of the ACE2 receptor, which facilitates viral entry into host cells, as well as use of medications to treat hypertension, have been implicated.
Cancer
Early in the pandemic, the Centers for Disease Control and Prevention (CDC) indicated that COVID-19 posed greater risks to patients with cancer. However, a JAMA Oncology study found that, after adjustment, patients with no recent cancer treatments had similar or better outcomes than patients without cancer (mortality OR 0.93). This was not true for patients who had received recent cancer treatment, which was associated with a significantly higher risk of death (OR 1.74, CI, 1.54-1.96), ICU stay (OR 1.69), and hospitalization (OR 1.19).9
There were also prognostic differences with worse prognosis in patients who had hematologic malignant neoplasms rather than metastatic solid tumors. These outcomes likely reflect the status and function of the immune system in these patients, rather than the presence or absence of a cancer diagnosis.
Lung Disease
Surprisingly, although asthma was initially thought to be a high-risk condition in relation to COVID-19, and was listed as such by the CDC, patients with well-controlled asthma did not appear to be at higher risk of contracting COVID-19, facing severe COVID-19-related illness, or death. However, there was a signal for increased COVID-19-related death in patients who had recently needed oral corticosteroids for their asthma.10 This was in stark contrast to those with COPD, in whom COVID-19 was twice as likely to be fatal.11
Fighting the Enemy: Vaccines, Boosters, and Treatments
As the pandemic evolved, and the virus change epidemiologically, scientists across the world utilized every tool in their toolbox to minimize morbidity and mortality from COVID-19 infection.
The most important of these was undoubtedly the advent of not one but multiple safe and effective COVID-19 vaccines that reduced infection, asymptomatic transmission, and, importantly, risk of severe COVID-19 illness requiring hospitalization. Despite newer variants with immune escape characteristics (such as Omicron), the vaccines augmented with a booster several months later allowed for a high level of protection against severe illness and death. Although the messenger RNA vaccines were associated with a rare but higher risk of myocarditis, especially in young men, the risk of myocarditis associated with COVID-19 infection remained much higher, and the American Heart Association and American College of Cardiology continued to recommend widespread vaccination and boosting for all Americans, especially those with preexisting CVD.12
In addition, during the course of the pandemic, multiple evidence-based treatments for COVID-19 evolved, including the advent of monoclonal antibodies and antiviral medications given early in the course of illness for infected high-risk patients who were not yet hospitalized but were at risk for progression to hospitalization.
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What Can Cardiologists Do?
In the face of two of our worst pathological enemies teaming up to impact human lives, cardiologists are among the most important specialists in the fight against COVID-19. Staying up to date on the latest guidance, which continues to evolve at lightning speed, is perhaps the most important first step for all cardiologists. Encouraging widespread masking, mitigation, and testing will be critical in the transition from pandemic to endemic.
We must also emphasize prevention through widespread vaccination and boosting, as well as adherence to plans for chronic disease management, including diabetes control, lipid lowering therapy, hypertension control, obesity and weight loss education, and maintaining a healthy diet and lifestyle. After all, loss of access to care has been one of the biggest impacts of the pandemic — one that will last long after the disease has become endemic.
For survivors of the SARS-CoV2 infection, regardless of the variant, long COVID and the cardiovascular implications of the disease are significant. Cardiologists should utilize ECG screening followed by echocardiographic or MRI assessments to diagnose and treat long COVID patients early.
One thing is certain: The epidemiology, diagnosis, prognosis, and management of this rapidly evolving virus will continue to advance as more data emerges. Staying abreast of the latest guidelines and treatment recommendations will be of utmost importance, both to our understanding of the virus and in providing optimal care for patients with preexisting conditions or elevated risk of cardiovascular disease.
References:
1. Kohli P, Virani SS. Surfing the waves of the COVID-19 pandemic as a cardiovascular clinician. Circulation. 2020;141:1733–1735(22). Published online May 5, 2020. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.047901.
2. John Hopkins University of Medicine. John Hopkins University of Medicine Coronavirus Resource Center. https://coronavirus.jhu.edu/. Accessed February 12, 2022.
3. Dan S, Pant M, Upadhyay SK. The case fatality rate in COVID-19 patients with cardiovascular disease: Global health challenge and paradigm in the current pandemic. Current Pharmacology Reports. Published online September 15, 2020. doi: 10.1007/s40495-020-00239-0 .
4. Basu-Ray I, Almaddah Nk, Adedayo A, et al. Cardiac manifestations of coronavirus (COVID-19). https://www.ncbi.nlm.nih.gov/books/NBK556152/
5. Dherange P, Lang J, Qian P, et al. Arrhythmias and COVID-19: A Review. Journal of American College of Cardiology: Clinical Electrophysiology. 2020;September, 6 (9) 1193–1204. https://www.jacc.org/doi/full/10.1016/j.jacep.2020.08.002.
6. Cariou B, Hadjadj S, Wargny M. Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: The CORONADO study. Diabetologia. 2020 63(10223). https://link.springer.com/article/10.1007/s00125-020-05180-x.
7. Wadman M. Why COVID-19 is more deadly in people with obesity—even if they're young. Science. https://www.science.org/content/article/why-covid-19-more-deadly-people-obesity-even-if-theyre-young#. Accessed February 12, 2022.
8. Mubarik S, Liu X, Eshak ES, et al. The association of hypertension with the severity of and mortality from the COVID-19 in the early stage of the epidemic in Wuhan, China: A multicenter retrospective cohort study. Frontiers in Medicine. Published online May 12, 2021. https://www.frontiersin.org/articles/10.3389/fmed.2021.623608/full. Accessed February 12, 2022.
9. Chavez-MacGregor M, Lei X, Zhao H, et al. Evaluation of COVID-19 mortality and adverse outcomes in US patients with or without cancer. JAMA Oncology. 2022;8(1):69-78. https://jamanetwork.com/journals/jamaoncology/fullarticle/2785677.
10. GINA Global Strategy for Asthma Management and Prevention. GINA guidance about COVID-19 and asthma. Ginasthma.org (https://ginasthma.org/wp-content/uploads/2021/03/21_03_30-GINA-COVID-19-and-asthma.pdf). Accessed February 12, 2022.
11. Meza D, Basil Khuder B, Bailey JI. Mortality from COVID-19 in patients with COPD: A US study in the N3C data enclave. International Journal of Chronic Obstructive Pulmonary Disease. August 2021:16 (2323—2326). doi.org/10.2147/COPD.S318000
12. American Heart Association. Additional COVID-19 vaccine recommended for all adults, especially in light of Omicron variant. Heart.org. https://newsroom.heart.org/news/additional-covid-19-vaccine-recommended-for-all-adults-especially-in-light-of-omicron-variant. Accessed February 12, 2022.
Dr. Payal Kohli, MD, FACC is a top graduate of MIT and Harvard Medical School (magna cum laude) and, as a practicing noninvasive cardiologist, is the managing partner of Cherry Creek Heart in Denver, Colorado.
The opinions, beliefs, and viewpoints expressed in this article are solely those of the author and do not necessarily reflect the opinions, beliefs, and viewpoints of GE Healthcare. The author is a paid consultant for GE Healthcare and was compensated for creation of this article.
