POST-COVID CARDIOVASCULAR EFFECTS
Post-COVID symptoms and prolonged impact on health are now surfacing as a major point of attention for both physicians and patients. Among these, effects on the heart and blood vessels, and their possible sequelae are concerning, needing awareness and care. Below are some possible cardiovascular effects based on a few limited studies.
MYOCARDIAL EFFECTS
Myocardium is the middle muscular layer of the heart enabling pumping action. Myocardial injury and inflammation is often seen in COVID patients, which when significant enough to affect heart functioning is called myocarditis. The term cardiomyopathy means any disease of the cardiac muscles or myocardial layer of the heart. So, myocarditis is also called inflammatory cardiomyopathy. The inflammation in such cases can also lead to scarring (fibrosis) that can decrease the pumping capacity of the heart, as well as disturb heart rhythm. This can manifest with symptoms such as chest pain, chest heaviness, tiredness, decreased work capacity, feeling breathless, and getting palpitations. Serious risks include heart failure and cardiac arrest (sudden death).
Chest pain was reported in up to ~20% of COVID-19 survivors at 2 months follow-up.
Palpitations and chest pain were ongoing in 9% and 5%, respectively, at 6 months follow-up in a post-acute COVID study.
Stress cardiomyopathy, a condition in which intense emotional or physical stress can cause rapid and severe heart muscle weakness, has been noted to be higher during the COVID pandemic time compared with pre-pandemic periods (7.8 versus 1.5–1.8%, respectively), although mortality and re-hospitalization rates in these patients were similar.
Myocardial inflammation may be present at rates as high as 60% at more than 2 months after a diagnosis of COVID (seen with preliminary data from MRI at a COVID-testing center), although the reproducibility and consistency of these data have been debated.
Myocarditis in 15% and previous myocardial injury in 30.8% was seen among participants in a study of 26 competitive college athletes with mild or asymptomatic SARS-CoV-2 infection, revealed by cardiac MRI.
HEART RHYTHM EFFECTS
These can include tachycardia (increased heart rate), bradycardia (decreased heart rate) and other arrhythmias (irregular heart rhythm and conduction defects). The normal heart rate is 60-100 beats/minute.
Arrhythmias (heart rhythm disturbances) can be seen as ‘re-entrant arrhythmias’ arising due to myocardial fibrosis or scarring, resulting from the inflammatory cardiomyopathy induced by the COVID virus. COVID may also perpetuate arrhythmias due to increased inflammatory mediators (cytokines- IL-6, IL-1 and TNF-α) affecting ‘ion channels’ on the cardiac muscle cells.
Postural orthostatic tachycardia syndrome (POTS) refers to symptoms like lightheadedness, fainting with rapid heartbeat (tachycardia) on standing up, which are relieved by lying down again. It occurs due to autonomic dysfunction and the release of adrenaline.
Transient sinus bradycardia is a possible manifestation of COVID and is important for close cardiovascular surveillance. It could be due to oxygen deficiency (hypoxia), inflammatory damage of cardiac pacemaker cells, and exaggerated response to medications. High levels of pro-inflammatory cytokines may act directly on the cardiac pacemaker also called the sinoatrial (SA) node, contributing to the development of bradycardia. This may be a warning sign of the onset of a serious cytokine storm.
Bradycardia due to medicines may also occur. Increased awareness of possible exaggerated bradycardia response is important to consider with the use of empiric medications that have ‘arrhythmogenic’ effects. Some patients may develop bradycardia with the use of favipiravir and remdesivir.
Relative bradycardia is a frequent clinical feature of COVID, which occurred in 56% of hospitalized patients with fever (febrile patients) in one study. This fact should be taken into account while evaluating febrile patients in the context of a possible SARS-CoV-2 infection. Relative bradycardia in non–critically ill patients does not appear to be associated with a worse clinical outcome.
VASCULAR EFFECTS
These occur due to the COVID virus itself and the resulting inflammation in the body causing micro-injury to the inner walls (endothelium) of the blood vessels (arteries and veins), and increasing the risk of thrombosis (clots). This can have a significant impact on those who already have risk factors like diabetes, high BP, high cholesterol/triglycerides and history of cardiovascular disease (including past history of heart attack, stroke or tests showing blockages/plaques in important blood vessels). Clots in arteries can cause stroke or angina/heart attack post-COVID.
A clot in veins is called venous thromboembolism (VTE) which can manifest as thrombosis of veins, or parts of the clot detaching loose (embolus) and lodging in the lung (pulmonary embolism) which can even be fatal. People who have had a long hospital stay or been immobilized for prolonged periods are at higher risk. Retrospective data on post-acute thromboembolic events, (although limited by small sample size, variability in outcome ascertainment and inadequate systematic follow-up), suggest the rate of venous thromboembolism (VTE) in the post-acute COVID-19 setting to be <5%, and commonly seen 3-6 weeks after discharge from hospital.
CAUSES OF IMPACT
- Direct effects of viral invasion
- Downregulation (suppression) of key receptors (like ACE2)
- Inflammation and body’s immunological reaction
- Myocardial scarring (fibrosis)
- Increased cardiometabolic demand, lower cardiac reserve and dysregulation of renin–angiotensin– aldosterone system (RAAS), a hormonal system that regulates BP, and fluid/electrolyte balance, and keeps up the proper functioning of the cardiovascular system.
- Dysfunction of autonomic nervous system and modulation of adrenaline release. (Autonomic nervous system is a component of the peripheral nervous system that regulates involuntary activities like heart rate, blood pressure, respiration, digestion, and sexual arousal. It has 2 divisions with often opposing effects: sympathetic, regulated by adrenaline and noradrenaline – increases heart rate, BP etc. and parasympathetic.)
- Thrombosis due to endothelial injury, activation of platelets and complement proteins, interaction of platelets with white blood cells, release of pro-inflammatory cytokines, disruption of normal coagulation pathways, and hypoxia.
Autopsy studies in 39 cases of COVID-19 detected virus in the heart tissue of 62.5% of patients. The subsequent inflammatory response may lead to death of cardiac muscle cells and the replacement of important cell-cell adherence proteins (desmosomal proteins) by fibrous-fatty substances.
MANAGEMENT CONSIDERATIONS
- Serial clinical and imaging evaluation with electrocardiogram (ECG) and echocardiogram (2D-Echo) at 4–12 weeks may be considered in those with cardiovascular complications during acute infection, or having persistent cardiac symptoms. Current evidence does not support the routine utilization of advanced cardiac imaging, and this should be considered on a case-by-case basis.
- Recommendations for competitive athletes with cardiovascular complications related to COVID-19 include abstinence from competitive sports or aerobic activity for 3–6 months until resolution of myocardial inflammation by cardiac MRI or blood cardiac troponin normalization.
- Despite initial theoretical concerns regarding increased levels of ACE2 and the risk of acute COVID with the use of RAAS inhibitors drugs (ACE inhibitors like enalapril, ramipril, and AR blockers like telmisartan, olmesartan), they have been shown to be safe and should be continued in those with stable cardiovascular disease. In fact, abrupt cessation of RAAS inhibitors may be potentially harmful. In patients with ventricular dysfunction, guideline-directed medical therapy should be initiated and optimized as tolerated. (Withdrawal of guideline-directed medical therapy was associated with higher mortality in the acute to post-acute phase in a retrospective study of 3,080 patients with COVID).
- Patients with postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia may benefit from a low-dose beta blocker for heart rate management and reducing adrenergic activity. Attention and consideration is warranted for the use of anti-arrhythmic medicines (like amiodarone) in patients with lung fibrosis post-COVID.
- Thromboprophylaxis extended to post-hospital discharge (up to 6weeks) and prolonged (up to 45 days) in those managed as outpatients may have a more favorable risk-benefit ratio in COVID given the noted increase in thrombotic complications during the acute phase. However, this is still an area of active investigation awaiting conclusive evidence. Elevated D-dimer levels (> twice the upper limit of normal), in addition to comorbidities such as cancer and immobility, may help to risk-stratify patients at the highest risk of post-acute thrombosis, however, individual patient-level considerations for risk versus benefit should dictate recommendations at this time. Direct oral anticoagulants (DOAC) and low-molecular-weight heparin (LMWH) are preferred anticoagulation agents. The role of antiplatelet agents such as aspirin as an alternative (or in conjunction with anticoagulation agents) for thromboprophylaxis in COVID has not yet been defined and is currently being investigated. Physical activity and ambulation should be recommended to all patients when appropriate. Therapeutic anticoagulation for those with imaging-confirmed VTE is recommended for ≥ 3months.
References:
Dr Samir Kubba, MD, DNB (Medicine), MNAMS, DM (Cardiology) is a Fellow of the American College of Cardiology (FACC), Society for Coronary Angiography and Interventions (FSCAI), and the European Society of Cardiology (FESC). He is Associate Director for Clinical and Interventional Cardiology at Max Super Specialty Hospital, Vaishali, Delhi and NCR.
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Inflammation of Heart Layers (Carditis) – Pericarditis, Myocarditis, Endocarditis