COVID-19 and the Heart: Insights From the Front Lines – TCTMD

As the number of COVID-19 casesand panicspreads throughout the globe, a picture is emerging as to what the direct cardiovascular effects of this particular coronavirus (SARS-CoV-2) might be and what the indirect impact will be on cardiologists and the patients in their care.

Clinicians on the front lines in the heaviest-hit areas of what has now been declared a pandemic by the World Health Organization (WHO) described to TCTMD what its like on the ground, and how they are coping.

It is a war that came completely unexpected and none of us would have ever imagined that Italy, and in particular Milan, would have been affected and that our healthcare system would have been facing almost a breakdown, Alaide Chieffo, MD (IRCCS San Raffaele Hospital, Milan, Italy), told TCTMD. We need to slow down the number of positives to be ableto take care of everyone. It is a war against time: increasing the number of beds, the intensive care units, supplies and equipment for assisted/mechanical ventilation, ECMO, but also masks to protect healthcare providers.

San Raffaele Hospital has been selected as a hub center for COVID-19, as well as for all cardiovascular emergencies, said Chieffo. As of March 9, 2020, atotal of82 COVID-19-positive patients had been admitted to the hospital, 19 in intensive care units, with a total possible capacity of 100 dedicated beds. Yesterday, she said in an email, all physicians from my hospital received the invitation on a voluntary basis to be reallocated to take care of COVID-19 patients.

It is a war that came completely unexpected and none of us would have ever imagined that Italy, and in particular Milan, would have been affected and that our healthcare system would have been facing almost a breakdown. Alaide Chieffo

Meanwhile, elective coronary procedures in the cath lab, where Chieffo is the research director and Matteo Montorfano, MD, is the clinical director, have been reduced by 80%. As a hub, San Raffaele is also the referral hospital for any patients with cardiovascular complications from the virus. We are looking to collect cardiac enzymes in order then to be able to detect the prevalence of cardiac injury, but so far it was referred to us only one 43-year-old female who came in to the emergency room for chest pain with ST changes but had a scan positive for pneumonia. She was found to be COVID-19-positive, but she had normal coronary arteries.

Meanwhile Junbo Ge, MD (Zhongshan Hospital, Fudan University, Shanghai, China), said things in China have turned a corner. He himself applied to travel to Wuhan City to help with patients there, but he ultimately stayed put in Shanghai where he has tele-consulted for physicians seeking help for patients with cardiac symptoms in Wuhan.

Late last week, he described for TCTMD the types of cardiovascular symptoms he and his colleagues are seeing. Despite early warnings that myocarditis might be one manifestation of COVID-19 infection, Ge said that an electron microscope specimen hed received from a pathologist in Wuhan showed no signs of direct virus infiltration of the myocardium.

We do see that a considerable proportion of patients with the coronavirus do have elevation of troponin, indicating myocardial injury, but this does not necessarily mean myocarditis, Ge said. When he spoke with TCTMD last week, hed tele-consulted on two patients, both of whom had blood tests indicating elevated C-reactive protein, CD4, CD8, and interleukin-6, pointing to an acute inflammatory response. This inflammation may cause multiorgan damage, not only myocardial damage, he stressed.

Ge also consulted on the case of a patient in Wuhan who developed myocardial infarction following contraction of coronavirus pneumonia. In this case, Ge said, he believes the patient likely had underlying atherosclerosis and ischemia conditions worsened secondary to viral hypoxemia.

Ges predictionso faris that patients, after recovering from COVID-19, will have normal heart function. There may be some evidence of lung fibrosis, but the myocardial injury were seeingthe troponin and pro-BNP elevationI believe they will normalize after discharge, he said.

During the peak of the epidemic in China, Ge told TCTMD, his hospital turned away all patients with chronic heart conditions, asking them to stay home, with some cardiac wards closed to allow for their use for COVID-19 admissions. As of last week, however, wards at Ges hospital had returned to normal function. He and others have been doing the majority of consultations by internet and telephone, Ge added, saying that one of advantage of being in China is the 5G network, which has facilitated these kinds of tele-consultations for patients with hypertension, stable coronary disease, and diabetes.

In the future, I think we will call this the cloud clinic or something like that, Ge said, saying it might be one of the few positives that could come out of this epidemic. That will play an important role in the future, especially for the follow-up of patients with chronic disease.

COVID-19 and the Heart

Late last week, the American College of Cardiology (ACC) released a clinical bulletin reviewing the cardiac complications of COVID-19 and the underlying comorbidities. Based on early case reports, the ACC is reminding physicians that the majority of patients hospitalized with the virus have cardiovascular, cerebrovascular, and diabetes-related comorbidities.

For example, in a single-center report on 99 patients in China, published in the Lancet, 40% of the cohort had cardiovascular or cerebrovascular disease and 12% had diabetes, noted the ACC. In a second series, also out of China and published last month in JAMA, nearly half of 138 hospitalized patients had at least one comorbid condition, with hypertension (31%), diabetes (10%), and cardiovascular disease (14.5%) being the three most common.

In a report from the Chinese Center for Disease Control and Prevention cited by the ACC in its bulletin, 10.5% of case fatalities occurred in patients with cardiovascular disease and 6% in patients with hypertension. Theres also a growing appreciation that patients who succumb to their infections are more likely to have underlying chronic conditions, including cardiovascular disease.

Mohammad Madjid, MD (UTHealth, Houston, TX), who has spent years researching the link between influenza viruses and cardiovascular disease, put it bluntly. Cardiologists need to be aware [that] a good proportion of their patients are going to get COVID-19 at some point, he predicted. They need to be vigilant.

Lessons From the Seasonal Flu

Speaking with TCTMD, Madjid stressed that any viral infection can be expected to impact the heart, and said ongoing research on the types of cardiac complications seen from seasonal flu outbreaks can shed light on the types of cardiovascular injuries expected from COVID-19. The first, as noted, is inflammation, which he stressed is systemic as well as localized at the arterial level. We know that influenza affects atherosclerosis in the arteries of animal models and it affects the myocardium. We also know from human and epidemiologic studies that, astonishingly, if you look at almost all epidemics and pandemics of influenza, more people die of cardiovascular causes than due to lung diseases or pneumonia-influenza mortality.

Cardiologists need to be aware [that] a good proportion of their patients are going to get COVID-19 at some point. They need to be vigilant. Mohammad Madjid

A second consideration in the setting of flu infection, which likely also extends to COVID-19, Madjid continued, is heart rhythm abnormalities secondary to viral infection. Our own research has shown that, for example, during flu season we have more ICD shocks in people who have an ICD.

The third important interaction between influenza and the heart to be on the lookout for is acute heart failure (HF), including cases caused by myocarditis, as well as HF exacerbation. Importantly, he stressedpartly in response to Ges reassurancesmyocarditis can be caused by direct infiltration of the virus, but can also be secondary to severe hypoxia and the cytokine storm mounted in response to the systemic infection. Madjid said hed spoken to colleagues in Tehran, the capital city of hard-hit Iran, whove told him anecdotally that they are seeing cases of fulminant myocarditis. Madjid noted, too, that a research letter published March 3, 2020, in Intensive Care Medicine comparing clinical features of COVID-19 survivors and nonsurvivors at two Wuhan city hospitals also concluded that some of the five patients who had died of circulatory failure secondary to myocardial damage in their 150-patient series had died of fulminant myocarditis.

Other preliminary, single-center series are trying to get a better handle on the extent of cardiac injury. A preprint study uploaded onto medRxiv.org (not yet peer-reviewed) describes clinical and radiographic features of myocardial injury in 41 consecutive COVID-19 patients admitted to Beijing Youan Hospital, China (two of whom died). Here, CT imaging of epicardial adipose tissue indicated cardiac injury in severe (four) and critical (three) cases, using the definitions set out by the National Health Commission in China. Patients in the critical group also experienced new-onset atrial fibrillation and high heart rates. Therefore, the monitoring of the heart functions of COVID-19 patients and applying potential interventions for those with abnormal cardiac injury-related characteristics is vital to prevent the fatality, the authors conclude.

Treatment and Care

A search of ClinicalTrials.gov indicates that are approximately 80 trials now recruiting patients for studies testing antiviral agents and vaccines or trying to understand different aspects of this disease process. For now, Madjid stressed, there are a number of other things cardiologists can be doing to protect patients that are clearly more vulnerable to this disease.

The most important thing to do, he said, is to make sure other guideline-directed medical therapy is optimized in CVD patients. We know that as the baseline risk goes down, the risk of the disease can be attenuated, and thats the key here.

Where indicated, judicious use of high-intensity statins is reasonable, he continued. You have to be careful because of the impact on liver function, but I would say maximally tolerated statins have a role to play, because we see a lot of inflammation here . . . and we know that statins reduce inflammation at the artery level, so that seems a reasonable approach.

Madjid pointed to speculation online and in the medical literature suggesting that angiotensin receptor blockers (ARBs) could potentially be used as COVID-19 therapeutics, based on a paper arguing that the angiotensin-converting enzyme 2 (ACE2) very likely serves as the binding site for SARS-CoV-2, the strain implicated in the current COVID-19 epidemic.

Madjid, however, dismissed this, calling it a flawed understanding of the virus. There is a lot of misinformation out there, he said. The ACE inhibitors and ARBs do not act on this receptor directly so they are not going to affect the activity of the virus for these cells. The proposed interactions of ACE inhibitors and ARBs with the virus is purely hypothetical with no reliable data to justify any deviation from current practice guidelines.

Patients should continue to receive these medications if indicated for their cardiovascular condition, but there is no evidence for extra benefit or extra harm in these patients, he said.

Last but not least, said Madjid, physicians should be reminding patients, particularly patients with chronic diseases, to get the seasonal flu vaccine, uptake of which hovers at 50% to 60% in the United States and is only slightly higher in people with cardiovascular disease. That should be more than 90%, he said, for patients with cardiovascular disease and other chronic diseases, as recommended by organizations like the US Centers for Disease Control and Prevention and the WHO.

We want to remind people that [COVID-19] is a disease for which we dont have a vaccine, we dont have a treatment for it, were very afraid of it, and rightfully so, Madjid said. We should be vigilant and maximize our use of guideline-directed medications. But influenza is rampant in the United States right now, it has killed more people in the United States so far than the whole of the people that have died of COVID-19 around the world, and yet we have a vaccine for it.

At a minimum, he said, the more people get the seasonal flu vaccine, the fewer people will come down with the seasonal flu, the less febrile disease that could lead to confusing and delayed diagnoses, and the more hospital beds that will remain open for people needing emergency care for novel coronavirus infection.

Chieffo added that she wanted to say a special thanks toall first-line healthcare providers, physicians, and nurses that are fighting this war against time. . . . I really wish that this nightmare will be over as soon as possible.

Photo Credit: A. Chieffo

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COVID-19 and the Heart: Insights From the Front Lines - TCTMD