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The global coronavirus pandemic has widespread implications for cardiovascular health. Since early in the course of the SARS-Cov-2/Covid-19 pandemic it was recognised that the clinical picture associated with the disease involved systemic illness and multisystem dysfunction. Cardiac complications in particular are relatively frequent. Moreover, patients with pre-existing heart disease appear to be at heightened risk of a severe clinical course if they develop Covid-19. In addition, some of the medications that were used for the treatment of patients with severe Covid-19 illness have cardiac side-effects, including QT-interval prolongation and cardiac arrhythmias.
More recently, observational data suggests that a high proportion of patients who have recovered from Covid-19 had changes on cardiac MRI during follow-up. In a broader sense, the coronavirus pandemic has had most wide-reaching consequences in relation to service provision in patients without Covid-19 infection. Many studies documented a dramatic decline not just in elective cardiac procedures – which would not have been unexpected – but also in presentations with acute coronary syndrome and number of patients undergoing diagnostic and interventional catheter procedures for this indication.
Myocardial injury seems to occur in about 20-to-30 per cent of patients with severe Covid-19 who require admission to hospital. Importantly, adverse outcomes – in terms of proportion of patients with acute respiratory distress syndrome (ARDS) and death – are higher in patients whose illness is complicated by myocardial injury. The pathogenesis of myocardial injury in severe Covid-19 is multifactorial and includes injury due to: (i) type 1 myocardial infarction (classical plaque rupture); type 2 myocardial infarction (including coronary artery supply/demand mismatch due to sepsis and shock, and microvascular dysfunction and thrombosis); (ii) viral myocarditis and myopericarditis; (iii) systemic inflammatory response syndrome or cytokine storm; (iv) right heart strain due to pulmonary embolism; and (v) stress (Takotsubo cardiomyopathy).
The management of patients with acute coronary syndrome (ACS) in the clinical circumstances pertaining during the first wave of Covid-19 proved extremely challenging, particularly in the worst hit regions. In certain areas, emergency systems were overwhelmed by large numbers of patients with advanced respiratory distress and patients had difficulties accessing care for other emergent conditions like myocardial infarction. As hospitals became significant amplifiers of the pandemic, triage protocols for ACS and care pathways had to be rapidly amended.
Complicating this, evidence emerged to suggest that a proportion of patients with undiagnosed Covid-19 presented initially with ACS with atypical features. Data from the Milan region in Italy showed that a high proportion of patients (>60 per cent) who were admitted to the cath lab with ACS and subsequently testing positive for Covid-19 had no evidence of obstructive coronary artery disease despite extensive changes on ECG. This suggested that acute Covid-19 could masquerade as ACS.
With the passage of time, some explanations for this latter phenomenon have emerged. Firstly, it has become clear that Covid-19 illness that is severe is associated with a significant prothrombotic state. This seems to be dependent on the severity of the clinical illness. Heightened thrombotic risk is explained by a constellation of clinical risk factors including acute illness, reduced mobility, volume depletion, liver and kidney dysfunction and haemodynamic compromise. Amplifying this risk is the systemic inflammatory response associated with the illness which seems to contribute to pronounced diffuse endothelial dysfunction.
Together these two factors can result in increased risk of venous thromboembolism (VTE) (including major pulmonary embolism), arterial thrombosis and/or embolism (including myocardial infarction), and disseminated intravascular coagulopathy. In fact, this double hit of intravascular thrombosis and microvascular dysfunction is likely a final common pathway for myocardial injury in a significant proportion of cases. Supportive evidence for this is emerging from autopsy studies. Although autopsy data has been somewhat slow to emerge due to logistical considerations associated with disease control, studies in selected patients reveal evidence of diffuse myocardial injury on macroscopic examination and microvascular thrombosis on light microscopy.
On the other hand, myocarditis with viral infiltration of cardiomyocytes has been somewhat less frequent than clinically suspected. Heightened thrombotic risk may also manifest as stent thrombosis in patients with a recent or remote history of coronary stenting.
Optimal management strategies for patients with cardiac complications of Covid-19 are a matter of debate. Patients with ACS and heightened risk remain best served by urgent diagnostic angiography with percutaneous intervention as required. Whether more intense or prolonged antithrombotic therapy is beneficial remains to be demonstrated (eg, longer periods of therapeutic anticoagulation, use of more potent antiplatelet agents, more frequent use of intravenous glycoprotein receptor antagonists). In view of the pathogenic considerations discussed, however, such approaches appear clinically reasonable though dedicated trials are lacking. Observational studies suggest an association between anticoagulation and improved clinical outcome.
Several large-scale trials investigating therapeutic anticoagulation in acutely unwell patients with Covid-19 in comparison with standard care conventional thromboprophylaxis are ongoing. Although primarily focused on prevention of VTE, they will likely be informative also in relation to arterial thrombotic events. Interestingly, clinical experience suggests that major bleeding is not a dominant feature of the clinical picture of severe Covid-19 infection.
Finally, interaction between investigational therapies for Covid-19 and anticoagulants including NOACs, vitamin K antagonists, and heparin, may be clinically relevant and must be considered in decision making.
In relation to chronic complications in patients who recover from Covid-19, recent interest has centered on myocardial abnormalities seen in a high proportion of patients undergoing cardiac MRI in a study conducted in Germany. Interestingly, most of the patients had a mild clinical course and did not require hospital admission. Analysis of signal intensity on cardiac MRI showed that 78 per cent of patients had abnormalities detected. Moreover, some evidence of reduced ejection fraction was seen in comparison with matched controls.
Although the findings are intriguing and somewhat concerning, additional data to replicate these findings is awaited. Moreover, the clinical implications of changes that might be regarded as rather subtle remain unclear. In fact, our research institute is investigating the feasibility of a trial to confirm or refute these findings in an Irish population of Covid-19 recovered patients.
Finally, the impact of the coronavirus pandemic on heart disease is likely to be greatest in how it affects patients not suffering from Covid-19. Surveys of cardiologists across Europe and worldwide indicated a significant reduction in hospital admissions for myocardial infarction and a relative increase in patients presenting later with advanced complications of heart attack, less frequently seen in the contemporary era of reperfusion therapy. An analysis from the UK showed a 40 per cent reduction in ACS admissions in the initial phase of the pandemic, with a subsequent rebound in Q2 2020 albeit to a level that remained 16 per cent lower year-on-year when compared with historical data.
Disruptions in upstream healthcare provision, including risk factor identification and management, opportunistic screening for uncontrolled risk factors, and referral for investigation and therapy of heart disease represents a significant clinical risk at a population level. It may well be that the impact of missed opportunities for care will be felt in a delayed wave of heart disease and heart failure in the months and years to come. One thing is sure, in relation to heart disease, in line with other areas of medicine and society, the impact of the Covid-19 pandemic will be indelible.
References on request
Q&A with Dr Angie Brown, Consultant Cardiologist and Medical Director of the Irish Heart Foundation (IHF)
Priscilla Lynch: Are you/the IHF concerned about growing reports of cardiac issues such as myocarditis presenting in younger, healthier people related to Covid-19?
Dr Angie Brown: The Irish Heart Foundation are concerned about any patients who develop a significant illness from Covid-19, so the reports of patients being seriously unwell from direct cardiac involvement from Covid-19 is particularly worrying, especially as there seems to be a preponderance of young people affected. Whilst the primary focus of management for patients with Covid-19 remains close monitoring of respiratory function, there have been high levels of cardiac dysfunction in emerging cross-sectional and observational analyses, suggesting the need for heightened awareness in patients who may require cardiac input as part of a multidisciplinary approach.
Are you aware of such cases in Ireland?
Yes, I am aware of some cases in Ireland occurring in younger people in their 20s and 30s.
What are the issues being experienced?
Severe forms of myocarditis can lead to heart failure (impair the heart’s ability to pump blood) and arrhythmias. The presentation can be with chest pain and dyspnoea (breathlessness). Some of the people affected by this have needed treating on ITU and some have required ventilation and other forms of heart support. Other people may have milder forms of cardiac involvement with relatively few symptoms.
According to one study out of the University of Frankfurt in Germany, more than half of patients studied who had Covid-19 were found to have ongoing cardiac inflammation. Researchers noted that more than two-thirds of the patients who participated in the study had a mild illness and recovered at home from Covid-19.
We know that other viruses can affect the heart [but] the concern now is that even with a mild case of Covid-19, there’s a possibility that there could be inflammation and damage to the heart.
Do young people need to be more aware of the cardiac risks associated with the Coronavirus?
We all need to continue to be careful and continue to follow the recommendations about hand hygiene, physical distancing, etc, and it is important for younger people to realise that though the vast majority will recover from Covid-19 should they contract it, that a small percentage of younger people will be seriously ill and may have a protracted recovery.
Do you have further comments on this issue?
There are a couple of studies that suggest that being infected with Covid-19 carries quite a high likelihood of having some involvement of the heart. We need further information so we know how long these changes persist.
Since the pandemic began, people with underlying cardiovascular problems such as high blood pressure, coronary artery disease, or heart failure have been known to be at higher risk for infection and death.
The connection between Covid-19 and blood clots emerged later, after doctors began connecting the pulmonary embolisms, strokes, and heart attacks they were seeing to the virus.
Taken together these findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of Covid-19.