|Year : 2020 | Volume
| Issue : 2 | Page : 98-113
Nigerian cardiac society recommendations on the management of cardiovascular diseases in the coronavirus disease 2019 (COVID-19) era
Mahmoud U Sani1, Funso A Adesanya2, Abiodun Adeoye3, Akinyemi Aje3, Adaobi Ikemeh4, Jameel I Ahmad5, Shehu A Kana6, Dike B Ojji7, John A Okeniyi8, Uvie U Onakpoya9, Sandra Ofori10, Elvis E Osobaye11, Ejiroghene M Umuerri12, Christopher S Yigwan13, Okechukwu S Ogah3
1 Department of Medicine, Bayero University Kano & Aminu Kano Teaching Hospital, Kano, Nigeria
2 Department of Nursing Services, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria
3 Department of Medicine, University College Hospital/University of Ibadan, Ituku/Ozalla, Enugu, Nigeria
4 Department of Internal Medicine, University of Nigeria Teaching Hospital, Ituku/Ozalla, Enugu, Nigeria
5 Department of Surgery, Bayero university Kano & Aminu kano Teaching Hospital, Kano, Nigeria
6 Depertment of Medicine, Aminu Kano Teaching Hospital, Kano, Nigeria
7 Department of Medicine, Faculty of Clinical Sciences, University of Abuja, and Cardiology Unit, Department of Medicine, University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria
8 Department of Paediatrics, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria
9 Department of Surgery, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria
10 Department of Internal Medicine, University of Port Harcourt and University of Port Harcourt Teaching Hospital, Choba, Rivers State, Nigeria
11 Department of Cardiology, Reddington Multi-Specialist Hospital, Victoria Island, Lagos, Nigeria
12 Department of Medicine, Delta State University Teaching Hospital, Oghara, Nigeria
13 Department of Paediatrics, University of Jos & Jos University Teaching Hospital, Jos, Nigeria
|Date of Submission||03-Jun-2020|
|Date of Decision||25-Jun-2020|
|Date of Acceptance||16-Aug-2020|
|Date of Web Publication||13-Nov-2021|
Prof. Mahmoud U Sani
Department of Medicine, Bayero University Kano and Aminu Kano Teaching Hospital, Kano
Source of Support: None, Conflict of Interest: None
The global COVID-19 pandemic has created in its wake an urgent need for a clear guide for managing cardiovascular diseases and the complications it causes on the cardiovascular system. In this regard, the Executive Council of the Nigerian Cardiac Society constituted a committee to develop guidelines on management of Coronavirus Disease 2019 (COVID 19) and Cardiovascular Diseases. These guidelines have been written to provide a simple approach to managing cardiovascular diseases among COVID 19 patients in Nigeria. It will also provide information about potential cardiac implications of COVID 19 based on evidence and offer early clinical guidance on the management, given the current uncertainty of COVID 19. We have intended that this brief write up and set of recommendations be useful not only for primary care physicians, residents and medical students, but also for all professionals who work as hands-on practitioners.
Keywords: Cardiovascular, COVID-19, guidelines, Nigeria, severe acute respiratory syndrome coronavirus 2
|How to cite this article:|
Sani MU, Adesanya FA, Adeoye A, Aje A, Ikemeh A, Ahmad JI, Kana SA, Ojji DB, Okeniyi JA, Onakpoya UU, Ofori S, Osobaye EE, Umuerri EM, Yigwan CS, Ogah OS. Nigerian cardiac society recommendations on the management of cardiovascular diseases in the coronavirus disease 2019 (COVID-19) era. Nig J Cardiol 2020;17:98-113
|How to cite this URL:|
Sani MU, Adesanya FA, Adeoye A, Aje A, Ikemeh A, Ahmad JI, Kana SA, Ojji DB, Okeniyi JA, Onakpoya UU, Ofori S, Osobaye EE, Umuerri EM, Yigwan CS, Ogah OS. Nigerian cardiac society recommendations on the management of cardiovascular diseases in the coronavirus disease 2019 (COVID-19) era. Nig J Cardiol [serial online] 2020 [cited 2022 May 23];17:98-113. Available from: https://www.nigjcardiol.org/text.asp?2020/17/2/98/330418
| Introduction|| |
COVID-19 is defined as an illness caused by a novel coronavirus now called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, formerly called 2019-nCoV), which was first identified amidst an outbreak of respiratory illness cases in Wuhan City, Hubei Province, China. On January 30, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a global health emergency. As such, it is imperative that health-care workers (HCW) and researchers across all disciplines be aware of the potential impact that this disease can have on their respective fields and the medical community at large.
It is known that viral infections such as influenza can destabilize and worsen cardiac conditions, and COVID-19 is not an exception. Reports have shown that over 40% of patients with COVID-19 have underlying cardiovascular (CV) or cerebrovascular disease., It has also been shown that COVID-19 infection can involve the CVS in many ways with different presentations. In an observational study from Wuhan, China, cardiac injury was present in 19.7% of patients with confirmed COVID-19 and was an independent predictor of in-hospital mortality (51% among patients with cardiac injury versus 4.5% among those without cardiac injury, P < 0.001). Cox regression also revealed more than a fourfold increased risk of death among patients with cardiac injury versus those without cardiac injury (hazard ratio, 4.26; 95% confidence interval [CI]: 1.92–9.49).
| Epidemiology|| |
The emergence of SARS-CoV-2, causing COVID-19 pandemic, has a significant impact on global healthcare. Since the beginning of the pandemic to date, COVID-19 has spread to over 212 countries and territories across the world. As at June 3, 2020, 11:32 h, there have been a total of 6,399, 876 COVID-19-confirmed cases reported globally (157,322 in Africa and 10,819 in Nigeria), with associated 380,662 deaths (4493 in Africa and 314 in Nigeria), giving crude case-fatality rates of 5.95% globally, 2.86% in Africa, and 2.90% in Nigeria. Johns Hopkins University is making current data available: https://www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6. It has also been noted that the mortality rates associated with COVID-19 is much higher than the most recent WHO estimate of seasonal influenza mortality rate of <0.1%, and may reach higher rates than what is currently being observed, especially in the elderly patients, those with comorbidities, and those with absent efficient medical care support.
In the phase of inadequate widespread testing, national surveillance, standardized data collection, and a possible sampling bias of sick hospitalized patients with comorbidities, it is very difficult to accurately estimate the prevalence of CVD in patients with COVID-19, especially because of marked variation in testing by country. A number of studies in the available literature suggest an association between preexisting CVD and severe COVID-19. For example, a meta-analysis of six studies of 1527 patients with COVID-19 reported the prevalence of hypertension, cardiac and cerebrovascular disease, and diabetes to be 17.1%, 16.4%, and 9.7%, respectively. In addition, the case fatality rate of 2.3% for the general population is much lower than that for patients with CVD: 10.5%; hypertension: 6.0%; and diabetes mellitus: 7.3%. Furthermore, data from the Chinese Centers for Disease Control indicate patients with underlying comorbid conditions have a heightened risk for contracting COVID-19. In addition, they also seem to have worse prognosis.,
While more than 80% of infected patients with COVID-19 experience mild symptoms and recover without intensive medical intervention, morbidity and mortality increase significantly with age, rising to 8.0% among patients aged 70–79 years and 14.8% in patients over 80 years. This cannot be overemphasized as age is the strongest risk factor for CVD.
| Pathophysiology|| |
The mechanism of COVID-19-associated CV injury is not well understood; however, one of the mechanisms is believed to be direct myocardial injury, whereby the virus enters myocardial cells via angiotensin-converting enzyme 2 (ACE2) receptors which are upregulated in people with CVD. This is supported by the report of viral genome found in myocardium. ACE-2 is a type I integral membrane protein which serves many important physiologic functions and is widely expressed in the lungs and CVS and plays a vital role in the immune system., It is thought to play a critical role in the cardioprotective arm of the renin-angiotensin aldosterone pathway. Studies have shown that coronaviruses including SARS-CoV-2, the causative agent of COVID-19 uses the ACE2 protein for cell entry. Its high expression in lung alveolar cells and CVS makes it the main entry site for the virus into human hosts and provides potential for respiratory and CV damage. After ligand binding, SARS-CoV-2 enters cells via receptor-mediated endocytosis in a manner akin to human immunodeficiency virus. ACE2 also serves a role in lung protection and therefore viral binding to this receptor deregulates a lung protective pathway, contributing to viral pathogenicity. In addition to the heart and lung, ACE2 is expressed in the intestinal epithelium, vascular endothelium, and the kidneys, providing a mechanism for the multiorgan dysfunction that is seen with SARS-CoV-2 infection. Other possible mechanisms of CV injury include excessive cytokine release triggered by an imbalanced response by type 1 and type 2 T-helper-cells, and hypoxemia secondary to respiratory dysfunction caused by COVID-19. The greatly increased metabolic demands that occurs in the presence of respiratory infection and hypoxia is also believed to impair myocardial function.
| Clinical Context|| |
COVID-19 has significant implications for the CV care of patients. First, those with COVID-19 and preexisting CVD have an increased risk of severe disease and increased mortality. These patients need to be quickly identified and isolated even in the outpatient settings where they should be properly triaged and their treatment prioritized.
Second, coronavirus infection has been associated with multiple direct and indirect CV complications including acute myocardial injury, myocarditis, arrhythmias, venous thromboembolism, acute coronary syndromes and heart failure. Reports have also suggested that acute cardiac injury characterized by elevation of cardiac biomarkers, electrocardiographic and echocardiographic abnormalities, is highly prevalent in patients with COVID-19 and is associated with more severe disease and worse prognosis. In addition, it is important to note potential overlapping symptomatology between ACS and COVID-19. While the predominant presenting symptoms of COVID-19 are respiratory, a case was reported of a patient in Italy who presented with chest pain and electrocardiographic changes of acute myocardial infarction, but was later found to be free of obstructive coronary artery disease after coronary angiography, but subsequently tested positive for COVID-19. There is, therefore, the need to develop patient care pathways and protocols for COVID-19 patients with ACS.
Third, therapies under investigation for COVID-19 may have CV side effects. Although there are no specific effective therapies approved for COVID-19 currently, a number of pharmacologic agents are being studied. As these drugs are being investigated, it is important to review their potential for CV side effects as well as interactions with other CV medications.
Finally, the provision of CV care may place HCWs in a position of vulnerability. Because CV HCWs are on the front-lines treating COVID-19-infected patients, all possible measures should be implemented to reduce the risk of exposure.
In these guidelines, we present a summary of CV complications of COVID-19 based on available data, various precautions and recommendations needed to be followed for carrying out cardiac procedures and surgeries, management of specific cardiac conditions, current concepts in the use of cardiac drugs in COVID-19, and lastly cardiac complications of potential drugs to be used in managing COVID-19.
| Cardiac Complications of COVID-19|| |
Evidence of CV complications of coronavirus infections has been documented in past epidemics, and are also documented in the ongoing COVID-19 pandemic. However, these cardiac complications are not as frequent nor as prominent as the respiratory manifestations of the novel disease. Cardiac complications are mainly seen in adults and are rare in children aged <17 years. Available published data are mostly from case reports and retrospective studies. To date, there are no published prospective studies on the cardiac complications of COVID-19 and currently, there are no published reports on the cardiac manifestations of COVID-19 from sub-Saharan Africa.
The cardiac complications of COVID-19 may be due to several mechanisms. These include direct myocardial damage, systemic inflammation, imbalance in myocardial cardiometabolic demand, plaque rupture and coronary thrombosis, adverse effects of various therapies, and electrolyte imbalance. There are unambiguous reports of worsened prognosis in COVID-19 patients with CV comorbidities.
| Acute Myocardial Injury|| |
Acute myocardial injury is a common CV manifestation in SARS-CoV-2 infection. In the context of COVID-19, it is defined as elevation of cardiac troponin above the 99th percentile of the upper reference value, new global or regional left ventricular wall motion abnormalities on echocardiography and unexplained arrhythmia or ST changes on electrocardiography., The causes of acute myocardial injury include myocarditis, stress cardiomyopathy, hypoxic injury, ischemic injury caused by cardiac microvascular damage or epicardial coronary artery disease (with plaque rupture or demand ischemia), and systemic inflammatory response syndrome (cytokine storm). In a study by Wang et al., 7.2% had acute cardiac injury out of 138 hospitalized COVID-19 patients. Guo et al. in a cohort of 416 hospitalized COVID-19 patients, reported that myocardial injury occurred in 82 (19.7%) which was determined by elevated high-sensitivity troponin I (TnI). Hospital mortality rate (42 of 82 [51.2%]) was higher in patients with myocardial injury compared with those without myocardial injury (15 of 335 [4.5%]). Furthermore, mortality rate also increased with higher TnI. Similar observations were reported by Shi et al., where myocardial injury in COVID-19 was associated with a fatal outcome., In another study, Huang et al. reported that of the 41 patients with confirmed COVID-19 pneumonic infection, five (12.2%) had elevated levels of high-sensitivity cardiac TnI level.
The patients with acute myocardial injury usually manifest with cough, fever, breathlessness, fatigue, chest pain, and palpitations, though sometimes can be nonspecific. In addition, they may also present with heart failure de novo or worsening chronic decompensated heart failure, thus the need for high index of suspicion. Laboratory investigations may show elevated TnI and T or HsTnT, HsTnI (markers of myocardial injury) as well as B-type natriuretic peptide/N-terminal B-type natriuretic peptide BNP/NT-proBNP (markers of hemodynamic myocardial stress) may be elevated. Electrocardiogram (ECG) may show sinus tachycardia, prolonged QTc, ST-T wave changes, and arrhythmias such as atrial fibrillation or flutter. Echocardiographic findings could include chamber dilatation, regional wall motion abnormalities and impaired peaked global longitudinal systolic strain. Early or late gadolinium enhancement may be seen on cardiac MRI. Treatment include standard COVID-19 treatment protocol for supportive care, ACE inhibitors (ACEI)/angiotensin receptor blockers (ARBs), oxygen therapy, and anti-arrhythmic agents.
| Myocarditis|| |
Viral myocarditis from COVID-19 is a plausible consequence of direct myocardial damage. However, thus far, there is no biopsy-proven viral myocarditis linked to COVID-19 in the few clinically suspected cases that have been reported.,, In Daegu, South Korea, a case of a 21-year old female with COVID-19-related myocarditis was reported. The diagnosis was based on her symptoms, elevated TnI and NT-proBNP levels, and multimodal cardiac images (echocardiography, cardiac computerized tomographic scan and cardiac magnetic resonance imaging [MRI]). In another case report, the histologic findings of endomyocardial biopsy of a 69-year-old with COVID-19 infection in cardiogenic shock showed low-grade myocardial inflammation suggestive of either a viremic phase or migration of infected macrophages from the lungs. Cases of fulminant myocarditis and myopericarditis with cardiac tamponade have also been described.
| Cardiac Arrythmias|| |
There have been few reports of cardiac arrhythmias in the context of COVID-19. In a case series of 138 patients infected with SARS-CoV2 in China, Wang et al. documented that (unspecified) arrhythmia occurring in 23 (16.7%). He went further to show that those who had arrhythmia were more likely to require care in the intensive care unit (ICU). Another report among 187 patients showed that malignant arrhythmia (ventricular tachycardia/ventricular fibrillation [VT/VF]) occurred in 11 (5.9%) of patients with COVID-19.
Patients with Brady or tachyarrhythmias present with the usual symptoms of palpitations, dyspnea, chest pain, fatigue, diaphoresis, presyncope or syncope. In patients with COVID-19, especially those with preexisting hypertension or CVD, a baseline ECG is warranted. Troponin monitoring can identify myocardial injury which increases the risk of malignant arrhythmias. Nonmodifiable factors that prolong QTc should be identified and modifiable ones like electrolyte abnormalities should be corrected. In addition, drugs which affect the QTc interval should be avoided as much as possible or carefully considered when absolutely needed. Management of the arrhythmia (atrial fibrillation, VT/VF, bradycardia) should follow the usual guidelines with careful consideration of the need for anticoagulation. Electrical cardioversion when hemodynamically stable should be performed with full personal protective equipment (PPE) to reduce aerosol transmission to the providing HCWs. In COVID-19 patients treated with antimalarials and/or antiviral agents daily ECGs are warranted for early identification of abnormalities.
| Acute Myocardial Infarction|| |
The potential mechanisms of acute myocardial infarction include plaque rupture following inflammation/increased shear stress as well as aggravation of preexisting coronary artery disease. In a case series of 18 patients from six hospitals in New York City, ST-segment elevation suggestive of acute myocardial infarction was reported. There were variations in the clinical characteristics, echocardiographic and angiographic profile of these patients. Ten (56%) of them had noncoronary myocardial damage. In addition to elevated troponins, all the patients had elevated D-dimer levels. Furthermore, 13 (72%) had in-hospital mortality giving credence to poor prognosis in patients with COVID-19 and CV complications. Cardiac catheterization, coronary angiography with or without Percutaneous coronary intervention (PCI) when indicated should be performed with full PPE and modification of the setting (“specific additional recommendations for cardiac catheterization services during COVID-19 pandemic”). Treatment for acute myocardial infarction should be done according to standard guidelines.
| Heart Failure|| |
Any of the mechanisms of myocardial dysfunction can lead to acute heart failure. Increased metabolic demand of a systemic disease can cause acute decompensation of preexisting stable heart failure. Myocarditis is speculated to be the most frequent cause of heart failure in SARS-COV-2 patients with CV complications., While fulminant myocarditis has been described to occur in COVID-19, other workers have documented postmortem samples (death being due to pulmonary complications and cardiac arrest) with few interstitial mononuclear inflammatory infiltrates without substantial damage., This observation led to a hypothesis that underlying structural cardiac disease is probably needed for emergence of a heart failure phenotype. This heart failure phenotype may range from a classical heart failure with preserved ejection fraction in the more earlier stages COVID-19 in the context of pulmonary complications and later in the form of acute systolic heart failure as a response to the cytokine phase of COVID-19. There is therefore a need for more understanding of the late stages of COVID-19 and development of heart failure. Until then, heart failure specialists must develop a structured approach to the care of such patients and be included early in protocols for care of these patients. Discontinuation of ACEIs or ARBs should be avoided, as has been stated by concerned societies.
In the elderly patients with COVID-19, physicians should avoid excessive fluid use and drugs that may alter salt and water balance such as NSAIDs. Elderly patients with underlying structural cardiac disease should be given adequate attention and be screened with appropriate biomarkers.
| Venous Thromboembolism|| |
Venous thromboembolism has been reported frequently in patients with COVID-19 infection.
The actual incidence of VTE in the novel coronavirus infection is currently not known. The majority of people with SARS CoV-2 infection develop a mild or uncomplicated illness while about 14% develop severe disease requiring hospitalization and oxygen support. Approximately, 5% require admission to an ICU. Those with severe disease are prone to developing hospital associated venous thromboembolism (HA-VTE) which includes VTE occurring in hospital and for up to 90 days post discharge. However, few studies have suggested a higher risk of coagulopathy in COVID-19 patients when compared to other medical patients who have chest infections and elevated D-dimer values. Pulmonary thrombosis was found at postmortem and was commonest among those with severe diseases that required ICU care. Cui et al. found 20 (25%) out of 81 COVID-19 patients developed deep vein thrombosis. The VTE group were older with higher D-dimmer, prolonged APTT, and low lymphocytes. Similarly, Klok et al., discovered 31% of 184 COVID-19 patients admitted in two Dutch ICU centers developed thrombotic complications with pulmonary embolism predominating (n = 25; 81%). There is a need for high index of suspicion for pulmonary thromboembolism (PTE) in patients with sudden worsening respiratory symptoms and oxygen desaturation. All COVID-19 patients requiring admission for isolation and treatment will benefit from pharmacological thrombo-prophylaxis.
The traditional risks for VTE also apply to patients with COVID-19, though there are other novel risks peculiar to them. These include immobility, acute inflammatory state leading to a hypercoagulable state, endothelial cell activation/damage due to binding of the virus to ACE2 receptor, hyperfibrinogenemia, low antithrombin, and pulmonary congestion with microvascular occlusion.
The optimal VTE prophylaxis is not known. Guidelines may be adapted for each locality based on pieces of evidence available for management of VTE. Low-molecular-weight heparins (LMWHs) or unfractionated heparins with or without mechanical prophylaxis is the preferred choice for anticoagulant in the management of COVID-19-related thrombosis. It is also agreed that those on thromboprophylaxis for a background chronic disease such as atrial fibrillation in the preventions of stroke should continue with their doses. However, because of possible drug-drug interactions between antiviral treatments and direct oral anticoagulants (DOACs), and difficulty in maintaining stable INRs in patients taking Vitamin K antagonists while unwell, these group of patients are advised to shift to enoxaparin or unfractionated heparin in severe renal impairment. Also, studies have suggested LMW heparin has an anti-inflammatory effect which can help in the management of the inflammatory processes associated with novel coronavirus infection. There has been another insinuation that FXa and FIIb cleave the spike protein of the virus thereby promoting the multiplication and infectivity of the virus. By inference, anticoagulation might inhibit SARS-CoV-2 replication.
Prevention and early management of VTE in COVID-19 patients may reduce morbidity and mortality, hence the following considerations may be helpful.
- Pharmacological thromboprophylaxis should be given to all immobilized and severely ill patients with COVID-19 infections unless otherwise contraindicated. For creatine clearance (CrCl) >30: Give LMWH while when CrCl <30 or acute kidney injury: Unfractionated heparin 5000 units SC BD or TDS or dose-reduced LMWH are recommended
- All completely immobilized patients would benefit from intermittent pneumatic compression in addition to pharmacological thromboprophylaxis. Mechanical thromboprophylaxis should be used alone if platelets <50,000 or bleeding
- PTE should be considered in patients with sudden onset of oxygenation deterioration, respiratory distress, and reduced blood pressure (BP).
- Patients taking DOACs or Vitamin K antagonist (e.g., warfarin) for stroke prevention in atrial fibrillation or previous VTE should be switched to LMWHs.
| Angiotensin-Converting Enzyme Inhibitors and Angiogtensin Receptor Blockers in COVID-19 Patients|| |
The renin–angiotensin–aldosterone system (RAAS) is very central in maintaining normal CV physiology, and in the spectrum of CVDs such as coronary heart disease, hypertension, heart failure and myocarditis. On the whole, the RAAS comprises renin, angiotensinogen, angiotensin II (Ang II), Ang II receptors (AT1 and AT2 receptors) and ACE., ACE as an enzyme plays a role in the generation of Ang II by catalyzing the extracellular conversion of Ang I.
ACE2, a homologue of the ACE enzyme was discovered 20 years ago. It can convert Ang II to Ang 1–7 or convert Ang I to Ang 1–9., While Ang II increases BP, Ang (1–7) is a vasodilator, and therefore the ACE2/Ang (1–7) axis has been suggested to act as a counter regulatory mechanism for the activation of the classical RAAS.
As the ACE2 receptor is the mechanism of entry for SARS-CoV2, some data have suggested that ACEI and ARBs may upregulate ACE2, thereby increasing susceptibility to the virus. In contrast other studies show that ACEI/ARBs may potentiate the lung protective function of ACE2, which is an angiotensin II inhibitor.,,
Therefore, the therapeutic implications for ACEIs/ARBs therapy during COVID-19 infection are unclear. Overall, there is insufficient data to suggest any mechanistic connections between ACEIs/ARBs therapy with contracting COVID-19 or with severity illness once infected.
In addition, COVID-19 is particularly severe in patients with underlying CVDs, and in many of these patients, active myocardial injury, myocardial stress and cardiomyopathy develop during the course of illness., RAAS inhibitors have established benefits in protecting the kidney and myocardium, and their withdrawal may risk clinical decompensation in high-risk patients. Furthermore, switching from a RAAS inhibitor to another antihypertensive therapy in stable patients may require careful follow-up to avoid rebound increases in BP levels. Also, selection of dose-equivalent antihypertensive therapies may be challenging in practice and may be patient-dependent. And small and short-lived periods of BP instability after a therapeutic change are not innocuous as they have been associated with excess CV risk, which may be quite important in patients with COVID-19.,
Based on the available evidence RAAS inhibitors should be continued in patients in otherwise stable condition who are at risk for, currently being evaluated for, or have COVID-19. This position is now supported by multiple specialty societies. Pending the availability of additional data on the treatment of high-risk patients with COVID-19, it might be unethical and dangerous for clinicians to prematurely discontinue proven therapies in response to hypothetical concerns that are not experimentally proven.
| Medications for COVID-19 in Patients With Cardiovascular Disease|| |
Although no definitive therapy has been established for the treatment of COVID-19, several trial therapies and re-purposed drugs are being used for symptomatic management of the disease state. Some of these medications have been found to interact with CV medication while others have been noticed to have cardiac side effects. A knowledge of these medications is, therefore, very important for the CV physician.
Nucleotide analogues – inhibitors of nonstructural proteins (remdesivir, favipiravir, emtricitabine, tenofovir, and ribavirin)
No CV toxicities or drug–drug interactions have been reported with remdesivir. Ribavirin, however, has the potential to affect anticoagulant dosing due to its variable effects on warfarin dosing.
Protease inhibitors – inhibitors of nonstructural proteins (lopinavir and ritonavir)
Both lopinavir and ritonavir have the potential to affect anticoagulant dosing. They may require dose reductions or avoidance of CYP3A mediated drugs such as rivaroxaban and apixaban., Lopinavir and ritonavir can also influence the activity of P2Y12 inhibitors through CYP3A4 inhibition, which results in decreased serum concentrations of the active metabolites of clopidogrel and prasugrel and increased serum concentrations of ticagrelor. They can also increase digoxin levels.
Chloroquine and hydroxychloroquine
Both chloroquine (CQ) and hydroxychloroquine (HCQ) are known to prolong QT interval with a propensity to cause arrhythmias especially drug-induced torsades de pointes or in worse case scenarios, drug-induced sudden cardiac death in at-risk individuals. These side effects are worsened when they are co-administered with other medications that cause QTc prolongation especially in the setting of COVID-19, such as azithromycin and/or lopinavir/ritonavir. CQ has the potential to cause intermediate-to-delayed myocardial toxicity with increased risk in those receiving higher doses and may present as restrictive or dilated cardiomyopathy or conduction system abnormalities. CQ may also potentiate the effects of β-blockers., It is recommended that both CQ and HCQ be withheld in patients with baseline QT prolongation (QTc ≥500 ms) or with known congenital long QT syndrome, and other QTc prolonging agents should be avoided whenever feasible.
They can lead to fluid retention, electrolyte abnormalities, and hypertension and may interact with warfarin.
It can lead to QTc prolongation with concomitant use of CQ and HCQ and azithromycin increasing the likelihood of QTc prolongation and possible arrhythmias.
The rationale for their use is because of their anti-inflammatory properties and plaque stabilization through HMG-CoA reductase inhibition. Concomitant use with lopinavir/ritonavir can increase the statin level and increase the risk for myopathy. It is recommended that statins should be continued in patients with known atherosclerotic CVD (ASCVD), diabetes or high-risk ASCVD if previously on statin unless in patients with active rhabdomyolysis. Dose adjustment may be necessary in patients receiving concomitant antiviral agents like lopinavir and ritonavir.
| General Precautions in The Management Ofcardiovascular Conditions in COVID-19|| |
HCWs who are involved in the management of patients with CVDs are at high risk of contracting COVID-19. This is because HCWs come in close proximity with their patients in the course of CV examination or performing procedures. Hence, if the patient is COVID-19 infected, HCWs are at increased risk as the burden of viral load in respiratory droplets during acts of coughing or sneezing can be enormous. In order to prevent the spread of COVID-19 amongst HCWs, it is important to have established protocols/guidelines on specific precautions during CV care.
The level of precautions of HCWs involved in the care of patients with CVD depends on the patient risk status, setting and the CV procedure performed.
Specific precautions in managing patients with CVD include the following:,
- Ambulatory settings: all outpatients and CV health care givers should have surgical masks. They should also do appropriate triaging of patients to assess their risk status (stratify into low risk and high risk for COVID-19) and act appropriately
- Emergency room (ER) settings: There should be local protocols to rapidly triage patients with respiratory symptoms. These protocols should be made available at the ER reception. All patients gaining access to the ER should wear face masks while HCWs should use N95 masks. HCWs should use surgical hand gloves, goggles, face shield, boots and the other components of PPE (with proper training on donning and doffing of PPE) when consulting high risk patients. Personnel should have their white coats on, shirts rolled up, and frequent use of soap-based hand wash or alcohol-based hand wash. Frequent cleaning of equipment that can serve as fomites such as stethoscope, sphygmomanometer, and thermometers after use must be done. Dedicated cardiac care holding rooms should be identified, sitting arrangements during cardiac consultation should uphold the social/physical distancing rule, patients should be educated on cough etiquette, personal hygiene, and so on, as much as possible
- Ward setting: All patients with provisional diagnosis of myocarditis or other CV condition should undergo swab test for COVID-19. Confirmed cases should be managed in a separate isolation/case management center and managed by use of dedicated medical equipment (BP apparatus, stethoscopes, thermometers). Full PPE should be used in managing suspected and confirmed cases
- Coronary care/ICUs: Since the patients admitted into the CCU/ICU are critical, there is high probability of performing aerosol producing procedures and use of devices. In this setting, a high threshold of protection should be applied to patients and a high sense of precautions on the part of HCWs applying all the WHO recommended general safety measures
- Patients who may need any elective procedure or intervention, which are unlikely to affect the management, should have the procedure/intervention postponed to minimize transmission.
| Minimal Precautions for Noninvasive Diagnostic Cardiology Procedures|| |
The provision of continuous cardiologic services is particularly crucial in this difficult time of COVID-19 pandemic. However, careful considerations about “Whom,” “Where” and “How” will potentially minimize the risks of transmission of the coronavirus to HCWs, the patients and the public.
- Whom: There should be cautious prioritization of indications for all investigative and interventional procedures on a case-by-case basis. ECGs, transthoracic echocardiograms (TTE), stress echocardiograms and transesophageal echocardiograms (TOE), cardiac MRI, cardiac computed tomograms (CT) and angiograms should only be performed if they are expected to provide clinical benefit and influence management.
- All studies and procedures determined as “elective” should be postponed and rescheduled [Figure 1]
|Figure 1: Suggested algorithm for determining indication and precautions before and during echocardiography., ED: Emergency department; EP: Electrophysiology; ICU: Intensive care unit; TEE: Transesophageal echocardiography; TTE: Transthoracic echocardiography; STRESS: Stress echocardiography|
Click here to view
- All studies and procedures identified as “non-elective” (urgent/emergent), the patients should be categorized based on their COVID-19 statuses as (minimal risk = not suspected, moderate risk = suspected, high risk = confirmed).
- Where to image: ECGs and ECHOs should be done at bedsides with the use of hand-held and portable devices to minimize patient transportation. Where feasible, equipment and rooms may be dedicated to COVID-19-confirmed cases.
- Personnel: some institutions may face a crisis state with reduced availability of trained staff and/or equipment. The performance and interpretation of ECG, ECHOs and other studies, especially those in suspected or confirmed COVID-19 cases, should be limited to essential personnel. Additionally, staff who may be particularly susceptible to severe complications of COVID-19 such as those aged 60 years and above, those with chronic health conditions such as asthma, diabetes and hypertension or are immunocompromised or are pregnant should be given due considerations to limit their exposure with patients suspected or confirmed to have COVID-19
- Trainees: elective rotations should be suspended, and restrictions should be placed on trainees who are not essential to clinical care
- Telemedicine: Telephony and telemedicine may be deployed to facilitate remote clinical review and opinions. Training and education can be moved “on-line” such as webinars and lectures
- Personal Protection: Prior knowledge of patients COVID-19 status will allow for the appropriate application of PPE and its conservation when not needed, in addition to reducing the exposure risk to personnel.
- Standard care for patients with minimal risks should involve handwashing or hand sanitization and use of latex gloves, surgical face mask, scrubs or clinical coats
- Droplet precautions include wearing of gown, gloves, head cover, facemask and eye shield
- Airborne precautions should involve (in addition to droplet precautions) wearing special masks (e.g., FFP2/N-95 or FFP3/N-99 respirator masks, or powered air-purifying respirator [PAPR] systems), and shoe covers.
- Ultrasound assisted physical examinations, point of care cardiac ultrasound, critical care echocardiography, limited and comprehensive traditional TTE should remain the focus of cardiac imaging during this period
- TOEs particularly have a heightened risk of spread of the SARS-CoV-2 as aerosolization of a large amount of virus due to coughing or gagging may be provoked. Thus, TOEs should be postponed or cancelled if an alternative imaging modality can provide the necessary information required. A cautious consideration of the benefit of a TOE examination should be weighed against the risk of exposure of healthcare personnel to aerosolization in a patient with suspected or confirmed SARS-CoV-2 and the use of PPE
- Similarly, treadmill or bicycle stress echo tests on patients with COVID-19 may lead to exposure due to deep breathing and/or coughing during exercise. These tests should generally be deferred or converted to a pharmacological stress echo
- The use of computed tomography, CT or MRI, MRI scanner to avoid an aerosolizing procedure should be balanced against the risk of transporting a patient through the hospital to the CT or MRI scanner, risk of staff infection, the need to disinfect the CT or MRI scanner and room, and iodinated contrast and radiation for CT, long scan times for MRI; and should only be performed if the expected information is critical for clinical management as against the above considerations
- Prolonged procedure times should be avoided to limit expose and risks of coronavirus transmission.
- Equipment: equipment care is critical in the prevention of coronavirus transmission. Echocardiogram machines, probes and ECG cable should be thoroughly cleaned, ideally in the patient's room and again in the hallway. Probes and machine consoles may be covered with disposable plastic and the use of ECG stickers may be waived. However, the advantage of use of these protective covers and waiver must be balanced against the potential for suboptimal images and prolongation of procedure time. Where feasible, dedicated equipment may be reserved for use of patients with COVID-19. Hand-held or smaller laptop-based scanners may have an advantage as they are easier to cover, clean, and disinfect than larger machines with higher capability, but use of these machines should be balanced against potential trade-offs in image quality and functionality. TEE probes should undergo cleaning in the room (including the handle and chord), then be transferred in a closed container to be immediately disinfected according to the manufacturer's recommendations
- Environment: Efforts must be stepped up to mitigate risks of coronavirus transmission in procedure and reading rooms. Operating, view and reading rooms should be well ventilated with only critical staff in attendance to avoid overcrowding. All equipment, probes and surfaces such as keyboards, monitors, mice, chairs, phones, desktops, and door knobs should be frequently cleaned, and decontaminated as per institutional and manufacturer protocols
- Movement of patients' relatives into the hospital/wards should be limited. Each patient relative, according to individual institutional policies, must follow infection control guidelines like meticulous and frequent handwashing or hand sanitization and use of appropriate PPE before entering into the hospital/wards.
| Specific Additional Recommendations for Echocardiography Services During COVID-19 Pandemic|| |
The provision of echocardiographic services remains crucial for the care of patients with suspected or confirmed COVID-19. Risk of contracting the disease can be minimized by carefully adopting measures to reduce the potential risks of transmission.
Echocardiographic exams should be planned ahead, based on indications, clinical information, laboratory data and other imaging findings to allow for a focused sequence of images – focused cardiac ultrasound study (FoCUS) – that help with management decisions.,
Scan times should be minimized by excluding students or novice practitioners from performing imaging. The aim is to reduce the time of exposure with the patient and to decrease the risk of contamination.,
At a minimum, focus in patients with verified or suspected COVID-19 should include the following:
- Left ventricle: Systolic global function (ejection fraction), signs of regional dysfunction, end-diastolic cavity dimension
- Right ventricle: Global function (right ventricular fractional area change or tricuspid annular plane systolic excursion), end-diastolic cavity dimension, tricuspid regurgitation pressure gradient (if possible)
- Valves: Gross signs of valvar disease, but only in cases of critical clinical importance should an in-depth evaluation be considered
- Pericardium: Thickening or effusion.
Imaging team should ensure rapid review and reporting of key findings in the patient's record and communicating them with the primary care team. Review of echo images in the echo lab by other clinical practitioners should be preferably done remotely while speaking with the cardiac physiologist or cardiologist by phone (audio/visual), or review images together via a webinar.
A face mask is recommended for infected patients undergoing echo examination provided institutional resources allow this strategy for source control.,
Appropriate application of PPE should be considered alike for both suspected and confirmed SARS-CoV-2 patients, and its conservation when not needed, in order to reduce the exposure risk to cardiac HCWs.
| Specific Additional Recommendations for Cardiac Catheterization Services During COVID-19 Pandemic|| |
The true prevalence of ACS in this COVID-19 pandemic may be underreported given the logistical challenges associated with limited testing, Cath lab availability, and the current campaigns consistently recommending individuals to “stay at home.” Patients are afraid to go to the hospital and become infected, so they prefer to stay at home, even with chest pain. Patients should be reassured about the safety of hospitals with areas for COVID-19 patients separated from the others. The message should be clear for patients to present to the hospital if they have chest pain. The risk of mortality for MI outweighs that of COVID-19 infection., The recommendations for the care and management of COVID-19 patients in the Cath Lab are as follows:
Ideally, a dedicated Cath lab should be located in a COVID-19 area of the hospital, but this may not always be possible. In the latter case, a “temporary” COVID-19 lab and procedure with a protected team needs to be set up for each patient. This might require a longer time.
For suspected or confirmed COVID-19 STEMI patients, there are two options: fibrinolytic therapy, or primary PCI [Figure 2]. Fibrinolysis is favored in China for local conditions and for risks of staff contamination. The same is not true in Europe and United States, where the superiority of PCI over thrombolysis is well established and where efficient networks between the hub and spoke Cath Lab centers are active., Fibrinolysis can be considered an option in Nigeria for STEMI patients who present within the window period and have no contraindication. This is further supported by the fact that access to rapid COVID-19 testing is limited, very few Cath Labs are available in Nigeria and staffing for the Cath Lab is inadequate. Overall, in the patient with known COVID-19 and STEMI, the balance of staff exposure and patient benefit will need to be weighed carefully.
|Figure 2: Patient flowchart for Cath Lab procedures in the COVID-19 pandemic. ??ACS: Queried acute coronary syndrome; STEMI: ST-segment elevation myocardial infarction; NSTEMI: Non ST-segment elevation myocardial infarction; PCI: Percutaneous coronary intervention; OMT: Optimal medical therapy; ICU: Intensive care unit; CCU: Cardiac/coronary care unit|
Click here to view
For non-ST elevation myocardial infarction (NSTEMI) patients, timing should allow diagnostic testing for COVID-19 infection (by either positive swab samples or lung CT scan) and for a more informed decision regarding infection control prior to cardiac catheterization.,
It has been suggested that in appropriately selected cases with known COVID-19 and NSTEMI (particularly for patients with Type 2 MI), conservative therapy may be sufficient based on the patient's risk. Similar protocol should be followed as for COVID-19 positive STEMI patients, if they cannot be managed by optimal medical therapy.,
Rapid discharge of primary NSTEMI (COVID-19 negative) patients following revascularization is recommended to maximize bed availability and to reduce exposure within the hospital. Follow-up of these patients via telemedicine could be satisfactory in most cases.,
Unstable NSTEMI patients whose instability is due to the acute coronary syndrome (rather than other factors) may be considered under the NSTEMI guideline outlined above.
For infection control and prevention, the COVID-19 status of every cardiac patient should be determined prior to admission into the Cath Lab. However, if a patient must go into the Cath Lab before the patient's COVID-19 test result is out, the patient's status must be known before moving the patient out of the Cath Lab. There should be safe and separate flow pathways to and from the Cath Lab for suspected and/or confirmed COVID-19 patients, and for COVID-19-negative patients.
Transportation of suspected or positive COVID-19 patients to the Cath Lab and from the Cath Lab to the appropriate area of the hospital (or a dedicated facility) should occur with protected staff following predetermined pathways and safe corridors.
In patients with active COVID-19 in whom primary PCI is to be performed, appropriate PPE should be worn as mentioned above. The use of PAPR systems may also be reasonable, especially for patients who may be vomiting (e.g., inferior STEMI), or those who may require CPR and/or intubation.
Importantly, the vast number of Cath Labs have either normal or positive ventilation systems and are not designed for infection isolation. Therefore, Cath Labs (except after a confirmed negative patient) will require a terminal cleaning following each procedure leading to delays for subsequent procedures.
At the end of each procedure, the necessary cleaning time for the Cath Lab should be allowed. Whenever possible, suspected or positive COVID-19 cases should be scheduled at the end of the working day, not to compromise the procedures which follow.
Dedicated room(s) should be prepared in the Cath Lab Suite, where all consumables and “unnecessary” equipment can be moved into to reduce contamination risk and make the cleaning of the procedure room as easy as possible.
Suspected or confirmed COVID-19 patients requiring intubation should be intubated prior to arrival to the catheterization laboratory. Furthermore, the threshold to consider intubation in a patient with borderline respiratory status may need to be lowered in order to avoid emergent intubation in the catheterization laboratory.
One measure which may help protect HCWs in the setting of cardiac arrest and chest compressions is the use of external mechanical compression devices to minimize direct contact with infected patients.,
| Precautions for Cardiac Surgeries in The COVID-19 Era in Nigeria|| |
The Coronavirus Disease 2019 (COVID-19) pandemic continues to portend unprecedented acute on chronic challenges to the Nigerian health care system in general and presents unique problems to the CV surgeon in Nigeria. With worldwide depletion of hospital resources, infection of health care personnel and critical shortages of vital resources including PPE, ventilators, and ICU beds. Capacity has also become limited to provide care for patients with serious comorbid conditions in need of urgent care not related to COVID-19. COVID-19 patients could be complicated by acute surgical emergencies such as cardiac tamponade or may be patients with preexisting structural heart disease requiring urgent surgical intervention who secondarily become affected by COVID-19.
There is at present no national guideline on elective and emergency surgeries, so these decisions are made by individual institutions. For the CV surgeon, the definition of an elective procedure needs to be elucidated in the following table [Table 1] which is adapted from the document produced by the Royal Colleges of surgeons in the England, Ireland and Edinburg and The Royal College of Physicians and surgeons of Glasgow.
| Specific Precautions for Cardiovascular Surgeons in Nigeria During COVID-19 Pandemic|| |
- As the head of the surgical team, the responsibility for adequate protection of the team lies squarely on the CV surgeon
- In the absence of widespread COVID-19 testing, consider every patient as COVID-19 positive
- Consider nonoperative management whenever it is clinically appropriate for the patient
- Consider waiting on results of COVID-19 testing in patients who may be infected, who live or have travelled through states with high burden of coronavirus cases
- Avoid emergency surgical procedures at night when possible due to limited team staffing
- The most senior member of the cardiac surgical team (but <60 years of age and without comorbidities such as hypertension, diabetes or immune compromise) should perform the procedures until the pandemic is over to minimize operating room time and maximize safety for both patients and healthcare staff. Training of the more junior staff members should be suspended until the peak is over
- Aerosol generating procedures (AGPs) increase risk to the HCW but may not be avoidable. For patients who are or may be infected, AGPs should only be performed while wearing full PPE including an N95 mask or PAPR that has been designed for the OR as well as face shields, elbow-length gloves and impervious disposable surgical gowns. Examples of known and possible AGPs include:
- Intubation, extubation, bag masking, bronchoscopy, chest tubes
- Electrocautery of blood, gastrointestinal tissue, any body fluids.
There should be no compromise in ensuring use of these PPEs for the surgeon, anesthetists, perioperative nurses, intensive care and ward nurses. If supply cannot be guaranteed for all the levels of care the patient will receive before discharge home from the hospital, consider postponing surgery or refer to an institution with good availability of PPEs.
It is important to reiterate that the type of PPE to be used on specific cases will depend on local institutional policy and resources. Adherence to guidelines on how to adequately don and doff PPEs is crucial in reducing spread of contamination.
Donning of personal protective equipment
- Surgical scrubs to be worn. These will need to be changed with each case if a COVID-positive case is treated or there is any concern about soiling
- No jewelry to be worn
- Scrub top to be tucked into scrub pants
- Thorough washing of hands for at least 20 s prior to initiating the donning process
- Shoe covers to be initially donned. Thereafter, prior to scrubbing, don the N95 respirator mask with the surgical scrub cap over the N95 mask
- Disposable face shields may also be used. Surgical safety goggles can be used as an alternative but will need to be sterilized after each case.
In addition to the above,
- HCWs should ideally have N95 respirator masks fit-tested and the correct size respirator mask should be used
- The scrub cap should cover both ears
- Prescription glasses/lead glasses on their own are not enough for protection
- The visor should adequately cover both eyes and provide some protection to the side of the face
- Put on usual radiation protection equipment as used.
- Thoroughly scrub hands to the level of the elbows using an anti-bacterial surgical scrub and warm water and prepare to gown
- For the disposable surgical gown to be worn, take care to ensure that gown sleeves do not go beyond wrists as it is put on and ensure that the top of the gown covers as much of the exposed neck area as possible
- We recommend a two-glove technique (closed and opened methods). Put on two pairs of gloves ensuring that both gloves fit snugly and cover the sleeves of the gown.
Doffing of personal protective equipment
- There is a very high risk of contamination and therefore another individual (Such as a circulating nurse) should watch you doffing the PPE and alert you to any possibility of contamination
- Remove the outer pair without touching the outside surface of the inner pair of gloves, and discard into a medical waste bin
- Remove shoe-covers and discard (performed more easily if sitting on a chair)
- Clean hands between every step of the procedure
- Remove the disposable gown by grasping the inside surface of the gown at the collar and rolling the gown away from you without touching the exposed surface of the gown
- Clean internal pair of gloves with alcohol
- Remove scrub cap
- Clean internal pair of gloves with alcohol and then remove
- Clean hands with alcohol
- Remove N95 respirator mask by pulling the elastics over one's head and discard the mask without touching the exposed surface of the mask. The respirator is removed last to reduce the likelihood of exposure to aerosolized droplets during doffing
- Wash hands with soap and warm water
- Radiation protection should be cleaned with an alcohol scrub, surgical scrubs should be washed, and the chair used during doffing of overshoes should be cleaned with an alcohol scrub
- There is a recommendation that you then take a shower, but one can aim to shower only before leaving the hospital.
| Telemedicine Program for Care of Cardiac Patients|| |
Due to the epidemiological necessity for distancing, medical centers are increasingly using telemedicine to care for new and established patients. This is recommended and is already being done by a number of institutions in Nigeria. The use of telemedicine can help to prevent transmission of COVID-19 as the patients are triaged while minimizing exposure of patients and HCWs to potential infection., Cardiac Outpatient Clinics can be performed via telemedicine through the telephone and/or online video platforms (provided proper documentation and medico-legal rules governing telemedicine are strictly applied).,,
Cardiologists and Cardiac Surgeons should ensure to manage their patient psychologically as so many factors, such as economic challenges, health issues, COVID-19 pandemic related social changes, may tend to affect patients' psychology and ultimately their overall health.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Biondi Zoccai G, Landoni G, Carnevale R, Cavarretta E, Sciarretta S, Frati G. SARS-CoV-2 and COVID-19: Facing the pandemic together as citizens and cardiovascular practitioners. Minerva Cardioangiol 2020;68:61-4.
Fried JA, Ramasubbu K, Bhatt R, Topkara VK, Clerkin KJ, Horn E, et al
. The variety of cardiovascular presentations of COVID-19. Circulation 2020;141:1930-6.
Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al
. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol 2020 Mar 25;5(7):802-810. doi: 10.1001/jamacardio.2020.0950.
Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis 2020;20:533-4.
Li B, Yang J, Zhao F, Zhi L, Wang X, Liu L, et al
. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol 2020;109:531-8.
The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Disease (COVID-19). China CDC Weekly 2020;2(8): 113-22.
Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al
. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020;395:507-13.
Ge XY, Li JL, Yang XL, Chmura AA, Zhu G, Epstein JH, et al
. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature 2013;503:535-8.
Wang H, Yang P, Liu K, Guo F, Zhang Y, Zhang G, et al
. SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway. Cell Res 2008;18:290-301.
Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: Molecular mechanisms and potential therapeutic target. Intensive Care Med 2020;46:586-90.
Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol 2020;17:259-60.
Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential effects of coronaviruses on the cardiovascular system: A review. JAMA Cardiol 2020;5(7):831-840. doi:10.1001/jamacardio.2020.1286.
Bansal M. Cardiovascular disease and COVID-19. Diabetes Metab Syndr 2020;14:247-50.
Qiu H, Wu J, Hong L, Luo Y, Song Q, Chen D. Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: An observational cohort study. Lancet Infect Dis 2020;20:689-96.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al
. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-1069. doi:10.1001/jama.2020.1585.
Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al
. Fourth universal definition of myocardial infarction (2018). Euro Heart J 2019;40:237-69.
Guo T, Fan Y, Chen M,Wu X, Zhang L, He T, et al. Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19) [published online ahead of print, 2020 Mar 27]. JAMA Cardiol. 2020;5(7):1-8. doi:10.1001/jamacardio.2020.1017.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al
. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.
Kim IC, Kim JY, Kim HA, Han S. COVID-19-related myocarditis in a 21-year-old female patient. Eur Heart J 2020;41:1859.
Inciardi RM, Lupi L, Zaccone G, Italia L, Raffo M, Tomasoni D, et al
. Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(7):819-824. doi:10.1001/jamacardio.2020.1096.
Kochi AN, Tagliari AP, Forleo GB, Fassini GM, Tondo C. Cardiac and arrhythmic complications in patients with COVID-19. J Cardiovasc Electrophysiol 2020;31:1003-8.
Hua A, O'Gallagher K, Sado D, Byrne J. Life-threatening cardiac tamponade complicating myo-pericarditis in COVID-19. Eur Heart J 2020;41:2130.
Bangalore S, Sharma A, Slotwiner A, Yatskar L, Harari R, Shah B, et al
. ST-segment elevation in patients with Covid-19 – A case series. N Engl J Med 2020;382:2478-80.
Zeng JH, Liu Y, Yuan J, Wang FX, Wu WB, Li JX, et al
. First case of COVID-19 infection with fulminant myocarditis complication. Case Report and Insights. Preprints 2020, 20200301 Preprints 2020, 20200301. [doi: 10.20944/ preprints202003.0180.v1].
Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al
. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020;8:420-2.
Mehra MR, Ruschitzka F. COVID-19 illness and heart failure: A missing link? JACC Heart Failure 2020 Jun;8(6):512-514. doi: 10.1016/j.jchf.2020.03.004.
Obe BH, Retter A, McClintock C. Practical guidance for the prevention of thrombosis and management of coagulopathy and disseminated intravascular coagulation of patients infected with COVID-19. Available from: https://thrombosisuk.org/downloads/T&H%20and%20COVID.pdf
. [Last Accessed 2020 April 20].
Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost 2020;18:1421-4.
Klok FA, Kruip MJ, van der Meer NJ, Arbous MS, Gommers DA, Kant KM, et al
. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 2020;191:145-7.
Tian X, Li C, Huang A, Xia S, Lu S, Shi Z, et al
. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg Microbes Infect 2020;9:382-5.
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al
. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181:271-80.e8.
Vasilieva N, Farzan M, Li W, Zhang C, He Y, Huang I, et al
. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J 2005;24:1634-43.
Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al
. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 2020;367:1260-3.
Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 2020;8:e21.
Sommerstein RG. Preventing a COVID-19 pandemic: ACE inhibitors as a potential risk factor for fatal COVID-19. BMJ 2020;368:M810.
Esler M, Esler D. Can angiotensin receptor-blocking drugs perhaps be harmful in the COVID-19 pandemic? J Hypertens 2020;38:781-2.
Udell JA, Zawi R, Bhatt DL, Keshtkar-Jahromi M, Gaughran F, Phrommintikul A, et al
. Association between influenza vaccination and cardiovascular outcomes in high-risk patients: A meta-analysis. JAMA 2013;310:1711-20.
Clar C, Oseni Z, Flowers N, Keshtkar-Jahromi M, Rees K. Influenza vaccines for preventing cardiovascular disease. Cochrane Database Syst Rev 2015;5:CD005050.
Rodrigues BS, David C, Costa J, Ferreira JJ, Pinto FJ, Caldeira D. Influenza vaccination in patients with heart failure: A systematic review and meta-analysis of observational studies. Heart 2020;106:350-7.
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al
. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al
. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020;395:1054-62.
Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo FX, Chong M, et al
. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington state. JAMA 2020;323:1612-4.
Wang Z, Chen Z, Zhang L, Wang X, Hao G, Zhang Z, et al
. Status of hypertension in China: Results from the china hypertension survey, 2012-2015. Circulation 2018;137:2344-56.
Lu J, Lu Y, Wang X, Li X, Linderman GC, Wu C, et al
. Prevalence, awareness, treatment, and control of hypertension in China: Data from 17 million adults in a population-based screening study (China PEACE Million Persons Project). Lancet 2017;390:2549.
Nielsen SF, Nordestgaard BG. Negative statin-related news stories decrease statin persistence and increase myocardial infarction and cardiovascular mortality: A nationwide prospective cohort study. Eur Heart J 2016;37:908-16.
DeCarolis DD, Westanmo AD, Chen YC, Boese AL, Walquist MA, Rector TS. Evaluation of a potential interaction between new regimens to treat hepatitis c and warfarin. Ann Pharmacother 2016;50:909-17.
Frost CE, Byon W, Song Y, Wang J, Schuster AE, Boyd RA, et al
. Effect of ketoconazole and diltiazem on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor. Br J Clin Pharmacol 2015;79:838-46.
Mueck W, Kubitza D, Becka M. Co-administration of rivaroxaban with drugs that share its elimination pathways: Pharmacokinetic effects in healthy subjects. Br J Clin Pharmacol 2013;76:455-66.
A scientific statement from the American Heart Association. Circulation 2016;134:E32-69.
Tönnesmann E, Kandolf R, Lewalter T. Chloroquine cardiomyopathy – A review of the literature. Immunopharmacol Immunotoxicol 2013;35:434-42.
KALETRA (R) Oral Film Coated Tablets, Oral Solution, Lopinavir Ritonavir Oral Film Coated Tablets, Oral Solution. Product Insert. AbbVie Inc. (per FDA), North Chicago, IL; 2013.
Kirkpatrick JN, Mitchell C, Taub C, Kort S, Hung J, Swaminathan M. ASE Statement on protection of patients and echocardiography service providers during the 2019 novel coronavirus outbreak. J Am Coll Cardiol 2020 Jun 23;75(24):3078-84.
British Society of Echocardiology. Clinical Guidance Regarding Provision of Echocardiography During the COVID-19 Pandemic; 2020. Available from: https://bsecho.org/covid19
. [Last accessed on 2020 Apr 20].
American Society of Echocardiology. ASE Statement on Protection of Patients and Echocardiography Service Providers During the 2019 Novel Coronavirus Outbreak; 2020. Available from: https://www.asecho.org/ase-statement-covid-19/
. [Last accessed 2020 Apr 20].
AIUM. Guidelines for Cleaning and Preparing External- and Internal-Use Ultrasound Transducers Between Patients and Safe Handling and Use of Ultrasound Coupling Gel; 2018; Available from: https://www.aium.org/officialStatements/57
. [Last accessed on 2020 Apr 20].
Skulstad H, Cosyns B, Popescu BA, Galderisi M, Salvo GD, Donal E, et al
. COVID-19 pandemic and cardiac imaging: EACVI recommendations on precautions, indications, prioritization, and protection for patients and healthcare personnel. Eur Heart J Cardiovasc Imaging 2020;21(6):592-598. doi: 10.1093/ehjci/jeaa072.
Driggin E, Madhavan MV, Bikdeli B, Chuich T, Laracy J, Bondi-Zoccai G, et al
. Cardiovascular considerations for patients, health care workers, and health systems during the coronavirus disease 2019 (COVID-19) pandemic. J Am Coll Cardiol 2020;75(18):2352-2371. doi: 10.1016/j.jacc.2020.03.031. Epub 2020 Mar 19.
Campo G, Rapezzi C, Tavazzi L, Ferrari R. Priorities for Cath labs in the COVID-19 tsunami. Eur Heart J 2020;41:1784-5.
Welt FG, Shah PB, Aronow HD, Bortnick AE, Henry TD, Sherwood MW, et al
. Catheterization laboratory considerations during the coronavirus (COVID-19) pandemic: From ACC's Interventional Council and SCAI. J Am Coll Cardiol 2020 May 12;75(18):2372-5. doi: 10.1016/j.jacc.2020.03.021. Epub 2020 Mar 19.
Shah PB, Welt FG, Mahmud E, Phillips A, Kleiman NS, Young MN, et al
. Triage Considerations for Patients Referred for Structural Heart Disease Intervention During the Coronavirus Disease 2019 (COVID-19) Pandemic: An ACC/SCAI Consensus Statement. Catheterization and cardiovascular interventions: Official journal of the Society for Cardiac Angiography & Interventions; 2020.
Stephens EH, Dearani JA, Guleserian KJ, Overman DM, Tweddell JS, Backer CL, et al.
COVID-19: Crisis management in congenital heart surgery. Ann Thorac Surg 2020;110(2):701-6.
John TJ, Hassan K, Weich H. Donning and doffing of personal protective equipment (PPE) for angiography during the COVID-19 crisis. Eur Heart J 2020;41:1786-7.
DeFilippis EM, Stefanescu Schmidt AC, Reza N. Adapting the educational environment for cardiovascular fellows-in-training during the COVID-19 pandemic. J Am Coll Cardiol 2020;75:2630-4.
Ferrari R, Di Pasquale G, Rapezzi C. 2019 CORONAVIRUS: What are the implications for cardiology? Euro J Prev Cardiol 2020. pii: 204748732091810-2047487320918102.
[Figure 1], [Figure 2]