Cardiovascular Disease, Myocardial Injury and Death in Patients with COVID-19

by Kat Hendrix

Evidence indicates that patients infected by the novel coronavirus and who have pre-existing cardiovascular conditions including heart failure, cardiovascular disease (CVD), cardiomyopathies and pulmonary hypertension experience a more severe COVID-19 course and worse outcomes.

A large case study of over 44,000 COVID-19 patients found an overall 2.3% fatality rate that reached 10.5% among those with underlying CVD. A review article found that, among people requiring hospitalization for COVID-19 infection, hypertension was the most common comorbid condition. That said, causal relationships are complex, and mechanisms of infection-related myocardial injury remain poorly understood. In some cases, it appears to be associated with overproduction of inflammatory cytokines which leads to multiple organ dysfunction including the cardiovascular system. However, other pathophysiological mechanisms may also contribute to myocardial injury.

While it may not be surprising that patients with pre-existing cardiovascular conditions have greater mortality, shorter times to death and longer times to recovery than patients without them, other findings raise more questions than they answer about the progress of COVID-19. For example, studies find that although infection-related myocardial injury is significantly associated with fatal outcomes, the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.

One study found myocardial injury, as demonstrated by elevated troponin T (TnT) levels, was observed in 27.8% of patients, and mortality was substantially higher in those with elevated TnT than in those with normal levels. The highest mortality rates were among patients with underlying CVD and elevated TnT; however, patients with underlying CVD and normal TnT levels experienced lower mortality rates than those with no underlying CVD but whose TnT levels were elevated during the course of their disease. Overall, patients with elevated TnT levels had substantially higher mortality than patients with normal TnT levels.

Other markers of myocardial injury, including dynamic escalation of N-terminal pro-brain natriuretic peptide and increased incidence of malignant arrhythmias were also seen in patients with elevated TnT levels. These findings highlight the role of myocardial injury in predicting outcomes in patients with COVID-19 and suggest that myocardial injury may play a greater role in fatal outcomes than the presence of underlying CVD in and of itself.

There are multiple potential causes for infection-related myocardial injury which can occur in the absence of respiratory symptoms. "We know that, in addition to respiratory failure, the mode of death can also be sudden myocardial insufficiency that is difficult to treat and resuscitate, says Jeffery Winterfield, M.D., associate professor of medicine, Hank & Laurel Greer endowed chair in electrophysiology, and director of the electrophysiology program at MUSC Health. “Essentially, patients die of cardiac arrest. But we don't yet know what causes this. It could be viral infection of the heart muscle cells. It could be that the body's immune reaction creates a cytokine storm and severe inflammation. Or it could be clots forming in the small blood vessels. It could very well be that, in some patients one thing is happening while in others, it's something else. The virus is still moving faster than the science."

Clarifying the association between CVD and outcomes in COVID-19 could be particularly important for populations with high prevalence of cardiovascular risk factors including hypertension, hypercholesterolemia and obesity, such as the southeastern Unites States.

"It's important to differentiate between the infection rate and disease severity," says Brian Houston, M.D., assistant professor of medicine in the division of cardiology at MUSC. "South Carolina is seeing exponential spread of the virus. We're just a little behind those areas that are the worst hot spots right now. It remains to be seen how the winter surge will play out in SC, and whether our higher prevalence of cardiovascular co-morbidities will result in a greater burden of severe cases.”

That said, we have learned that screening for underlying cardiovascular risk factors and markers of myocardial injury is useful in stratifying infected patients who need more intensive interventions. "We've had numerous discussions based on the rapidly evolving evidence on myocardial injury and infarction with COVID-19," says Winterfield. "The MUSC catheterization labs are well prepared, and we've developed a plan to mitigate the risks of performing procedures on infected patients. We're also prepared to evaluate patients who are admitted with cardiac symptoms based on their history and key clinical findings like an ECG along with, in some cases, biomarkers of myocardial injury. We use those factors to guide our decision-making, since we now know that if there's evidence of myocardial injury, the patient tends to get much sicker and has a worse prognosis."

Although a lot remains to be learned about the novel coronavirus, it is important for physicians and other trusted healthcare professionals to proactively dispel rumors and mistaken ideas that are circulating about the virus and its treatment.

"Young people are not free of risk of bad outcomes including pulmonary and cardiac complications if they become infected," says Houston. "Many patients in ICUs around the U.S. are younger than 50. We've all personally seen or taken care of young patients who are ventilated with organ dysfunction."

A U.S. study of outcomes in 3,222 young adults ages 18-34 who were hospitalized for COVID-19 found that 21% required intensive care, 10%) required mechanical ventilation, and 2.7% died. In addition, 3% of those who survived had to be discharged to a post-acute care facility for rehabilitation and further recovery.

It is important to communicate to everyone, particularly people with underlying cardiovascular risk factors, that it is imperative to follow recommendations for stopping viral spread by washing your hands, wearing a face covering and maintaining physical distance of at least 6 feet from other people. This is essential because, although vaccines are coming soon, they are not widely available yet. In addition, there is currently still no treatment for COVID-19.

"There is very limited trial data for medications. And we need to be clear that the role of hydroxychloroquine and azithromycin in treating COVID-19 is limited,” explains Winterfield. “One thing we do know is that this combination of medications has the potential to provoke dangerous and lethal arrhythmias because it reduces the heart's ability to re-polarize. We also know that, in some instances, the heart's capacity to reset and re-polarize is genetically determined. So, those two particular medications, which are known to disrupt the re-polarization process, are very dangerous in some patients."

The ability to measure and monitor patients' viral loads was an essential treatment guide during the HIV/AIDS pandemic. However, the novel coronavirus is moving faster than the discovery process that may eventually lead to development of viral assays and anti-viral medications.

"We do need to control viral loads, but the science isn't there yet. Currently, everything we’re doing is supportive and descriptive," says Winterfield. "We're all going back to school and learning this field together right now. A year ago, there was no literature at all about this–it didn't exist."

With all of the world's foremost scientists and researchers focused on this virus, vaccines have been developed and approved at record pace, but even with these and other treatment advances there is a great deal still to learn about how to optimize outcomes in infected patients.

"I want to point out that scientists are making heroic efforts to understand this virus and find treatments for it," says Houston. "Even though it may feel slow, the science on this is actually moving at breakneck pace. And, we have to remember that bad data is worse than no data–it's more dangerous than no data. So, we have to move fast, but only as fast as is safe. We want good data."