Esc, Covid p2

J_ID: Customer A_ID: EHAB697 Copyedited by: Manuscript Category: Special Article Cadmus Art: OP-EHEA21070
European Heart Journal (2021) 00, 1–45 SPECIAL ARTICLE

doi:10.1093/eurheartj/ehab697
ESC guidance for the diagnosis and

management of cardiovascular disease
during the COVID-19 pandemic: part 2—care
Downloaded from https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehab697/6429145 by guest on 05 January 2022

pathways, treatment, and follow-up
The Task Force for the management of COVID-19 of the European Society of
Cardiology
Received 23 April 2021; revised 8 July 2021; editorial decision 10 September 2021; accepted 13 September 2021
Aims Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus
disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe.
The aim of this two part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and
management of cardiovascular (CV) disease in association with COVID-19.
...................................................................................................................................................................................................
Methods A narrative literature review of the available evidence has been performed, and the resulting information has been
and results organized into two parts. The first, which was reported previously, focused on the epidemiology, pathophysiology,
and diagnosis of CV conditions that may be manifest in patients with COVID-19. This second part addresses the
topics of: care pathways and triage systems and management and treatment pathways, both of the most commonly
encountered CV conditions and of COVID-19; and information that may be considered useful to help patients
with CV disease (CVD) to avoid exposure to COVID-19.
...................................................................................................................................................................................................
Conclusion This comprehensive review is not a formal guideline but rather a document that provides a summary of current
knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommenda-
tions are mainly the result of observations and personal experience from healthcare providers. Therefore, the in-
formation provided here may be subject to change with increasing knowledge, evidence from prospective studies,
and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recom-
mendations provided by local and national healthcare authorities.
..
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..
* Corresponding authors. Tel: þ44 1865 743743, Fax: þ44 1865 743985, Email: colin.baigent@ndph.ox.ac.uk (C.B.); Tel: þ41 31 632 21 11, Fax: þ41 31 632 47 70, Email:
stephan.windecker@insel.ch (S.W.)
This article has been co-published with permission in the European Heart Journal and Cardiovascular Research. V C The European Society of Cardiology 2021. All rights reserved.
The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style. Either citation can be used when citing this article.
2 C. Baigent et al.
Graphical Abstract
ESC Guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic
Part 2 – Care pathways, treatment and follow-up
Protective measures for healthcare personnel

and patients in cardiology and triage systems

Risk categorization of invasive procedures
Management/treatment pathways
Treatment of SARS-CoV-2 infection
Patient information
...................................................................................................................................................................................................
Keywords ACE2 • Acute coronary syndromes • Arrhythmias • Biomarkers • Cardiogenic shock • COVID-19 •
Heart failure • Myocarditis • Venous thromboembolism • Pulmonary embolism • Thrombosis
..
Introduction .. (CAD), valvular heart disease (VHD), acute and chronic heart failure
.. (HF), and arrhythmic heart disease may be categorized. Management
..
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV- .. and treatment pathways for the most important CV disease (CVD)
2) causing coronavirus disease 2019 (COVID-19) reached pandemic
.. manifestations that may affect COVID-19 patients are summarized in
..
levels in March 2020 and has caused repeated waves of outbreaks .. detail in Section Management/treatment pathways, including acute
across the globe. COVID-19 shares many manifestations of a system-
.. coronary syndrome (ACS) and chronic coronary syndrome (CCS),
..
ic disease and has major implications for the cardiovascular (CV) sys- .. acute and chronic HF, VHD, hypertension, pulmonary embolism, and
tem, which are summarized in a two part review entitled European
.. arrhythmias. This is followed by an overview of various therapeutic
..
Society of Cardiology (ESC) Guidance for the Diagnosis and .. agents under evaluation to treat SARS-CoV-2 infections highlighting
Management of CV Disease during the COVID-19 Pandemic.
.. the important issue of drug–drug interactions, particularly as it relates
..
The second part of the document addresses the topics of protec- .. to proarrhythmic properties, such as QTc (corrected QT interval)
..
tion measures, triage systems, risk categorization of procedures, .. prolongation. Useful information for patients and updates on vaccina-
management and treatment pathways, therapeutic strategies for .. tions are summarized in the final chapter.
..
SARS-CoV-2 infections, and patient information. Owing to the highly .. While the document is comprehensive, it is not a guideline but ra-
contagious nature of the SARS-CoV-2 virus, appropriate protection .. ther a guidance document. The recommendations are the result of
..
of healthcare professionals (HCP) and patients in different encoun- .. observations and personal experience from healthcare providers.
ters, such as ambulatory care setting, hospital wards, emergency .. The present publication provides a summary of the guidance until
..
room visits, and intermediate and intensive care units, is of pivotal im- .. March 2021. Therefore, the information provided here may be sub-
portance. Depending on the extent of pandemic involvement in vari- .. ject to change with increasing knowledge, evidence from prospective
..
ous regions, prioritization of specialized procedures according to .. studies, and changes in the pandemic. Likewise, the guidance pro-
degree of urgency gains prominence, and this document provides .. vided in the document should in no way interfere with recommenda-
..
guidance on how invasive procedures for coronary artery disease . tions provided by local and national healthcare authorities.
ESC guidance for the diagnosis and management of CVD during COVID-19: Part 2 3
..
Management/treatment pathways .. scarcity. If resources available are insufficient to enable all patients to
.. receive the ideally required treatment, then fundamental principles
This section provides guidance on the specialist management of
..
.. should be applied in accordance with the following rules of
patients with CV conditions, while general guidance on protective .. precedence:
measures and care pathways for healthcare personnel and patients in
..
.. (1) Equity: Available resources are to be allocated without discrimin-
cardiology is provided as Supplementary material online. ..
.. ation (i.e. without unequal treatment on grounds of age, sex, resi-
.. dence, nationality, religious affiliation, social or insurance status, or
..
Cardiogenic shock .. chronic disability). The allocation procedure must be fair, objective-
.. ly justified, and transparent. With a fair allocation procedure, arbi-
..

.. trary decisions, in particular, can be avoided.
Key points .. (2) Preserving as many lives as possible: Under conditions of acute scar-
.. city, all measures are guided by the aim of minimizing the number of
• Management of cardiogenic shock (CS) and out-of-hospital ..
cardiac arrest (OHCA) is critically time-dependent, .. deaths. Decisions should be made in such a way as to ensure that as
requiring a dedicated network and multidisciplinary
.. few people as possible become severely ill or die.
expertise. ... (3) Protection of the professionals involved: Therefore, triage proto-
• .. cols are needed to maximize benefits and relieve HCP from impro-
Resource allocation should still try to deliver a standardized ..
team-based approach including availability and feasibility of .. vising decisions about whom to treat or making those decisions in
mechanical circulatory support (MCS). .. isolation.
• Invasive coronary angiography (ICA) remains the mainstay
..
.. Triage strategies, based on current evidence and a previously
of treatment. However, special considerations need to be ..
taken into account to minimize the risk of widespread .. established critical care triage protocol developed by working groups
nosocomial infections. .. for use during a worldwide influenza pandemic,10 are summarized in
•
..
In patients with concomitant COVID-19, escalation to MCS .. Table 1. Specific recommendations are provided for patients with and
should be carefully weighed against the development of .. without concomitant infection in Figure 1. Two scenarios will be
coagulopathy associated with COVID-19 and the need for ..
specific treatment (prone position) required for acute lung
.. considered:
..
injury. .. (1) Non-infected patients and
• In case of requirement for MCS, extracorporeal membrane ..
oxygenation should be the preferred temporary MCS .. (2) Possibly infected/COVID-19-positive patients.
..
because of the oxygenation capabilities. .. The infection should be suspected according to recently defined
• In case of acute renal failure, continuous renal replacement .. epidemiological and clinical criteria.11
should be used restrictively according to established ..
criteria.
..
..
• Daily sequential organ failure assessment and therapeutic ..
intervention scoring system scores should be assessed for .. ST-segment elevation myocardial
..
most critical patients, to improve decision-making. .. infarction
• The safety of HCP is of predominant importance to avoid .. The COVID-19 pandemic should not compromise timely reperfu-
any HCP infections ..
• SARS-Cov-2 infection should be excluded throughout two
.. sion of ST-segment elevation MI (STEMI) patients.12–14 In line with
.. current guidelines, reperfusion therapy remains indicated in patients
negative tests performed using a reverse transcriptase- ..
polymerase chain reaction (RT-PCR). For intubated .. with symptoms of ischaemia of <12 h duration and persistent ST-
patients, a tracheal aspirate would additionally be required .. segment elevation in at least two contiguous electrocardiogram
(see Supplementary material online, Section 1 and
..
.. (ECG) leads.5 Concurrently, the safety of HCP should be ensured.15
Supplementary material online, Section 2). .. To that purpose, and in the absence of previous SARS-CoV-2 testing,
• When the patient cannot be placed in the supine position, ..
it may be reasonable to provide cardiopulmonary
.. all STEMI patients should be managed as if they are COVID-19 posi-
.. tive. The main principles of STEMI management in the COVID-19
resuscitation with the patient in the prone position, ..
particularly in patients with advanced airway and circulatory .. pandemic are the following (Figure 2):
support.1,2 ..
.. (1) The maximum delay from STEMI diagnosis to the reperfusion of
..
.. 120 min should remain the goal for reperfusion therapy under the
.. following considerations:
.. a. Primary percutaneous coronary intervention (PCI) remains the
CS and OHCA are time-dependent diseases in need of relevant ..
resources, trained systems, and dedicated networks for optimal out- .. reperfusion therapy of choice, if feasible within this time frame
.. and performed in facilities approved for the treatment of
come. In general, treatment of CS and OHCA should follow current ..
guidelines and current evidence.3–9 However, it should be considered .. COVID-19 patients in a safe manner for healthcare providers
.. and other patients.
that in an overwhelmed critical care system stressed by the pandemic .. b. Primary PCI pathways may be delayed during the pandemic (up
COVID-19, it will not be possible for all patients to receive intensive ..
.. to 60 min in some networks experience) due to delays in the
care unit (ICU) treatment due to limited resources. This leads to diffi- .. delivery of care and the implementation of protective measures.
cult situations based also on the four widely recognized principles of ..
.. c. If the target time cannot be met and it is not contraindicated, fi-
medical ethics (beneficence, non-maleficence, respect for autonomy, .. brinolysis should be performed in accordance with ESC guide-
and equity), which are also crucial under conditions of resource
.. lines recommendations.5
4 C. Baigent et al.
Table 1 Detailed inclusion and exclusion criteria for triage in intensive care unit upon admission
Inclusion criteria:
• Requirement for invasive ventilator support.
• Requirement for hemodynamic support with vasoactive agents (noradrenaline-equivalent dose >0.1 lg/kg/min) or mechanical support.
• Requirement for renal replacement therapy.
If at least one criterion is fulfilled, check for exclusion criteria.

Exclusion criteria:
• Patients’ end of life decision preferences.

• Unwitnessed cardiac arrest, witnessed cardiac arrest, not responsive to electrical therapy, recurrent cardiac arrest.
• Metastatic malignant disease.
• End-stage neurodegenerative disease.
• Severe and irreversible neurological event or condition.
• Chronic condition:
• GOLD group D COPD,
• Cystic fibrosis or pulmonary fibrosis with baseline PaO2 <55 mmHg, and
• Cirrhosis, Child-Pugh score >7.
• End-stage kidney disease on dialysis with refractory symptoms despite active medical management treatment.
• Severe dementia.
• Estimated survival <12 months.
If not even one criterion is met and ICU beds are not available, check for additional exclusion criteria.
Additional exclusion criteria to be checked if no ICU beds are available:
• Severe trauma.
• Severe cerebral deficits after stroke.
• Moderate dementia (confirmed).
• Estimated survival <24 months.
• Chronic condition:
• home oxygen therapy and
• Cirrhosis with refractory ascites or encephalopathy > stage I.
• Age >80 years.

• Age >75 years and at least one criterion:
• Cirrhosis,
• Stage III chronic kidney disease KDIGO, and
• NYHA Class >II heart failure.
If neither of these criteria is fulfilled, consider to withdraw ICU support from patients who arrived earlier to save those with better prognoses.
Criteria for little or no likelihood of benefit with ICU treatment (occurrence of at least one criterion):
• Occurrence of two new significant organ failures not present on admission.
• No improvement in respiratory or hemodynamic status.
• Advanced multiple organ failure defined by an increase in SOFA score (>_25% compared to admission values after at least 10 days of treatment) associ-
ated with accumulated TISS >_500.
COPD, chronic obstructive pulmonary disease; FEV, forced expiratory volume in 1 s; FIO, fraction of inspired oxygen; GOLD, global Initiative for chronic obstructive lung disease;
ICU, intensive care unit; KDIGO, Kidney Disease: Improving Global Outcomes; NYHA, New York Heart Association; PaO2, partial pressure of arterial oxygen; SOFA, Sequential
Organ Failure Assessment; SpO2, oxygen saturation measured by pulse oximetry; TISS, therapeutic intervention scoring system; TLC, total lung capacity; VC, vital capacity.
(2) As SARS-CoV-2 test results are not immediately available in STEMI

.. should be taken to avoid potential infection of other patients and
..
patients, any STEMI patient should be considered potentially .. HCP.
infected. .. (4) Consider immediate complete revascularization if indicated and ap-
..
(3) All STEMI patients should undergo testing for SARS-CoV-2 as soon .. propriate to avoid staged procedures and reduce hospital stay.
as possible following first medical contact irrespective of reperfu- .. (5) All physicians involved in the management of patients with STEMI
sion strategy, at the latest upon admission to the ICU post primary
.. should be familiar with indications, contraindications, and dosage of
..
PCI. Until the result of the test is known, all precautionary measures . fibrinolysis and adhere to established administration protocols.5
Management of patients with cardiogenic shock/out-of-hospital cardiac arrest
Detection of SARS-CoV-2 in respiratory specimens upon admission

Consider patients as potentially infected until test results
SARS-CoV-2 results
Negative Positive or suspected
Treat as usual Dedicated network

Well-equipped and trained staff
Dedicated network Prioritize HCWs’ protection
Well-equipped and trained staff Be more restrictive with MCS,
consider ECMO if strictly needed
Fever or clinical sign of infection
Test for SARS-CoV-2
Figure 1 Management of patients with cardiogenic shock/out-of-hospital cardiac arrest during COVID-19 pandemic. COVID-19, coronavirus dis-
ease 2019; ECMO, extracorporeal membrane oxygenation; HCW, healthcare worker; MCS, mechanical circulatory support; SARS-CoV-2, severe
acute respiratory syndrome coronavirus 2.
..
Left ventriculography should be considered during catheterization .. in the epidemics.16 In geographic territories with significant pandemic
if echocardiography has not been performed before catheterization .. involvement, testing for SARS-CoV-2 should be performed as soon
..
laboratory admission or is not feasible soon after the procedure. .. as possible following first medical contact, irrespective of treatment
The treatment of the non-culprit lesions should be managed .. strategy, to allow HCP to implement adequate protective measures
..
according to patients’ clinical stability as well as angiographic features .. and management pathways (see Supplementary material online,
of those lesions. In the presence of persistent symptomatic evidence .. Section 1). Patients should be categorized into four risk groups (i.e.
..
of ischaemia, subocclusive stenoses, and/or angiographically unstable .. very high risk, high risk, intermediate risk, and low risk) and managed
non-culprit lesions, PCI during the same hospitalization should be .. accordingly (Figure 3).
..
considered. Treatment of other lesions should be delayed, planning a .. For patients at high risk, medical strategy aims at stabilization while
new hospitalization after the peak of the outbreak.5 .. planning an early (<24 h) invasive strategy. The time of the invasive
..
.. strategy may, however, be longer than 24 h according to the timing of
Non-ST-segment elevation acute .. testing results.
..
coronary syndromes .. Patients at intermediate risk should be carefully evaluated taking into
The management of patients with non-ST-segment elevation ACS
.. consideration alternative diagnoses to Type I myocardial infarction (MI),
..
should be guided by the risk stratification and intensity of involvement . such as Type II MI, myocarditis, or myocardial injury due to respiratory
6 C. Baigent et al.
Patients with STEMI during COVID-19 pandemic
Type to access to care

Self-presenting and/or
STEMI network
hospitalized patients
(ambulance)
with COVID-19
Transport to hospitals with At hospitals with At hospitals without

24/7 cath lab service 24/7 cath lab service 24/7 cath lab service
Timely primary Timely primary

Y Y
PCI possible PCI possible
N N
Fibrinolysis Primary PCI Fibrinolysis
General recommendations
Only hospitals equipped to manage patients with COVID-19 should maintain 24/7 cath lab service
for primary PCI
Any STEMI patient should be managed assuming positive COVID-19 status
Perform fibrinolysis if not contraindicated
Figure 2 Management of patients with STEMI during COVID-19 pandemic. COVID-19, coronavirus disease 2019; PCI, percutaneous coronary
intervention; STEMI, ST-segment elevation MI.
distress or multiorgan failure or Takotsubo. In the event any of the dif-

.. catheterization laboratories or operators, non-invasive conservative
..
ferential diagnoses seem plausible, a non-invasive strategy should be .. management might be considered with early discharge from the hos-
..
considered and coronary computed tomography angiography (CCTA) .. pital and planned clinical follow-up.
should be favoured, if equipment and expertise are available. .. Patients with troponin rise and no acute clinical signs of instability
..
When there is a positive SARS-CoV-2 test, patients should be .. (ECG changes, recurrence of pain) might be managed with a primarily
transferred for invasive management to a COVID-19 hospital .. conservative approach.17,18 Non-invasive imaging using CCTA may
..
equipped to manage COVID-19-positive patients. At times of high .. speed up the risk stratification and avoid an invasive approach allow-
demand on the infrastructure and reduced availability of .. ing for early discharge.19,20
..
Patients with NSTE-ACS during COVID-19 outbreak
Very high risk High risk Intermediate risk Low risk

Haemodynamic instability Established diagnosis of Established diagnosis of Any condition not listed
or cardiogenic shock NSTEMI based on cardiac NSTEMI based on cardiac in the other risk status

Recurrent/ongoing troponins troponins
chest pain refractory
And at least 1 of the And at least 1 of the
to medical therapy
following: following:
Life-threatening
arrhythmias or cardiac Dynamic ST/T changes Diabetes mellitus or
arrest (symptomatic or silent) renal insufficiencya
Mechanical complications Recurrent symptoms LVEF <40% or
of myocardial infarction congestive heart failure
Acute heart failure Early post-infarction
Recurrent intermittent angina or prior
ST-elevation PCI/CABG
Test for SARS-CoV-2

Test for SARS-CoV-2
If positive, transfer to COVID-19 equipped hospital
Immediate invasive Early invasive after

strategy (follow test result Non-invasive testingb Non-invasive testing
the STEMI pathway) (target <24 h)
Figure 3 Recommendations for the management of patients with NSTE-ACS in the context of COVID-19 outbreak. CABG, coronary artery by-
pass graft; COVID-19, coronavirus disease 2019; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NSTEMI, non-ST-segment-eleva-
tion MI; PCI, percutaneous coronary intervention; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. aEstimated glomerular filtration
rate <60 mL/min/1.73 m2. bCoronary computed tomography angiography should be favoured, if equipment and expertise are available. In low-risk
patients, other non-invasive testing might be favoured in order to shorten hospital stay. It is suggested to perform left ventriculography during cath-
eterization if echocardiography not performed before catheterization laboratory admission.
..
Chronic coronary syndromes .. infection.21 Potential impact of chronic aspirin therapy has been ques-
.. tioned. However, at the low dose administered in CCS, aspirin has
HCP managing patients with CCS in geographical areas heavily ..
affected by the COVID-19 pandemic should consider the following .. very limited anti-inflammatory effect. Therefore, CCS patients should
.. not withdraw aspirin for secondary prevention.
main points: ..
.. Statin therapy has been variably associated with favourable out-
• CCS patients are generally at low risk for CV events allowing the .. comes in patients admitted with influenza or pneumonia.22,23 On the
deferment of diagnostic and/or interventional procedures, in most
..
.. other hand, patients with COVID-19 have been reported to develop
cases. .. severe rhabdomyolysis or increased liver enzymes.24 In these latter
• Medical therapy should be optimized and/or intensified depending ..
.. cases, it may be prudent to temporarily withhold statin therapy.
on the clinical status. ..
• Remote clinical follow-up should be warranted to reassure .. For CCS patients treated with antihypertensive drugs please refer
patients and capture possible changes in clinical status that might .. to Section Hypertension.
..
require hospital admission in selected high-risk profile patients. ..
..
.. Non-invasive testing
..
Practical considerations of medical therapy .. Non-invasive testing in patients with CCS is tailored upon different
Nonsteroidal anti-inflammatory drugs have been identified as a po-
.. clinical presentations.25 In regions with a high rate of SARS-CoV-2 in-
..
tential risk factor for serious clinical presentation of SARS-CoV-2 . fection, evaluation of asymptomatic CCS patients with non-invasive
8 C. Baigent et al.
testing should be postponed in order not to expose these patients to

.. to patients). Physicians could therefore address most of the patients’
..
an unnecessary risk of infection or overload the healthcare systems. .. concerns related to continuation or changes in medical therapy.
For symptomatic patients with suspected CAD and a pre-test
.. Possible onset/recurrence of unstable symptoms should be estimated
..
probability of 5–15%, functional imaging for the detection of myocar- .. within the clinical history of the patient to weigh the need for hospi-
dial ischaemia or CCTA is normally recommended as initial tests to
.. talization and diagnostic testing.
..
diagnose CAD. In regions experiencing a critical situation and medical ..
..
systems overloaded by the COVID-19 pandemic, CAD screening, .. Invasive assessment and revascularization
even in symptomatic patients, should probably be postponed in the .. Symptomatic patients with very high clinical likelihood of obstructive
..
majority of patients. Yet, if necessary, depending upon local availabil- .. CAD are generally referred to ICA without prior non-invasive diag-
.. nostic testing.25 However, medical treatment should be attempted

ity and expertise, CTA should be preferred (see Guidance Part 1).
..
However, the increased workload of computed tomography (CT) .. first to reserve ICA with possible ad hoc revascularization only in
departments should be acknowledged; they have been heavily dis- .. case of clinical instability, especially in regions where healthcare sys-
..
rupted by the high request of pulmonary CT for patients with .. tems are heavily overloaded by patients with COVID-19.26
COVID-19. In addition, feasibility/accuracy of CCTA might be ham- .. Revascularization, either by PCI or by coronary artery bypass graft
..
pered in patients with COVID-19 for the common occurrence of .. (CABG), can be postponed in most CCS patients. Healthcare sys-
tachycardia and, at times, severe renal dysfunction. In case CCTA is ..
.. tems might identify COVID-19-free hospitals serving as hubs for
not suitable (e.g. inability of heart rate control) or available, non- .. selected CCS patients in whom invasive and surgical procedures can-
invasive testing should be postponed. Alternative imaging modalities ..
.. not be postponed. In selected patients, hybrid revascularization
should be discouraged during the acute pandemic phase unless se- .. CABG/PCI or even full-PCI can be considered by the heart
vere ischaemia is suspected, to minimize the access of the patients to ..
.. team based on the patient’s clinical condition and local situation (see
healthcare system (single photon emission computed tomography/ .. Table 2).
Positron emission tomography) or to prevent close contact between
..
..
patients and personnel (stress echocardiography). .. Heart failure: acute, myocarditis,
For known CCS patients, clinical follow-up should be done mostly
..
.. chronic, left ventricular assist device, and
via tele-health (a dedicated telephone line should be made available ..
.. transplantation
.. Patients with CV comorbidities, namely HF, are at increased risk of
..
.. the more severe presentation and complications of COVID-19.
Table 2 Management of chronic coronary syndromes .. Chronic HF is associated with a greater risk of hospitalization, re-
during COVID-19 pandemic
..
.. quirement of mechanical ventilation, and mortality. Acute HF may
..
Continuation of medications in CCS patients is recommended during .. occur as a major complication in patients hospitalized for COVID-19.
..
COVID-19 pandemic ..
Follow-up of CCS patients via tele-health is recommended .. Acute heart failure
..
Revascularization of CCS patients must be postponed in low- to ..
intermediate-risk patients ...
Postponing of non-invasive testing of CCS patients should be consid- .. Key points
..
ered during COVID-19 pandemic ..
CT angiography should be preferred to non-invasive functional testing .. • Acute HF may complicate the clinical course of COVID-19,
..
during COVID-19 pandemic .. • particularly in severe cases.
Underlying mechanisms of acute HF in COVID-19 may
Screening for SARS-CoV-2 infection should be considered before ..
.. include the following: acute myocardial injury due to
cardiac surgery with nasopharyngeal swab and CT scan .. ischaemia, infarction or inflammation (myocarditis), acute
Revascularization of high-riska CCS patients may be considered dur- .. respiratory distress syndrome (ARDS), acute kidney injury
..
ing COVID-19 pandemic .. and hypervolemia, stress-induced cardiomyopathy, and
PCI may be considered over CABG in selected patients during
.. tachyarrhythmia. Acute myocarditis with direct
.. demonstration of SARS-CoV-2, inflammatory infiltrate, and
COVID-19 pandemicb .. myocardial necrosis is, however, rare.27,28
..
Identification of COVID-19-free hospitals may be considered as ‘Hub’ .. • COVID-19 pneumonia may lead to the worsening
for cardiac surgery .. haemodynamic status due to hypoxaemia, dehydration, and
..
Invasive management of CCS in SARS-CoV-2-positive patients should .. • hypoperfusion.
be deferred until the patient has recovered, whenever possible .. Since symptoms of COVID-19 and acute/worsening chronic
.. HF can be similar, distinguishing these two entities is
CABG, coronary artery bypass graft; CCS, chronic coronary syndrome; COVID-
.. challenging. In addition, the two conditions may coexist.
.. Clinical presentation, pre-existing CV comorbidities, and
19, coronavirus disease 2019; CT, computed tomography; ICU, intensive care ..
unit; PCI, percutaneous coronary intervention; SARS-CoV-2, severe acute re- .. chest imaging findings suggestive of HF (e.g. cardiomegaly
spiratory syndrome coronavirus 2. .. and/or bilateral pleural effusion) are of utmost importance.
a
Patients with high-risk symptoms and/or coronary anatomy and/or large ischae- .. Significantly elevated B-type natriuretic peptide (BNP)/N-
mia as assessed by Heart team. .. terminal B-type natriuretic peptide (NT-proBNP) levels
b
To shorten hospital stay and keep ICU beds available for patients with COVID- ..
19.
.. also suggest acute HF, although increased levels of
.. natriuretic peptides may also be found in COVID-19
.
.. 25.6 ng/L) compared to those with non-severe course.42 In add-

patients in the absence of HF or left ventricular (LV) ..
systolic dysfunction. Prudent use of bedside point-of-care .. ition, troponin levels remained high in non-survivors throughout
or transthoracic echocardiography should be considered, .. the clinical course and increased with illness deterioration.31 A his-
keeping in mind the prevention of contamination of
..
.. tory of HF was more frequently noted in patients with, compared
personnel and/or equipment.29 ..
• The treatment of acute HF in patients with SARS-CoV-2 .. to those without, acute myocardial injury (14.6% vs. 1.5%).43
infection should be equivalent to those without COVID-19, .. Acute myocardial injury was also more frequently associated with
..
and attention should be given to early detection and .. significantly elevated NT-proBNP levels (median 1689 pg/mL).43 In
treatment of complications, including the need for non- .. a Spanish registry of 245 patients hospitalized for COVID-19, ele-
invasive or invasive ventilation, bleeding events, and cardiac ..
arrhythmias.29,30
.. vated troponin I levels were observed in 17.1%.44 On multivariate
.. analysis, elevated troponin I was associated with higher mortality

..
.. [odds ratio (OR), 4.93; 95% confidence interval (CI), 1.24–19.52;
.. P = 0.023], HF (OR, 4.28; 95% CI, 1.30–14.07; P = 0.017) and the
..
Data on acute HF in COVID-19 are still scarce. In an earlier report .. combined outcome of mortality or HF in patients without a his-
from China, 23% of all hospitalized patients developed HF, while HF .. tory of heart disease (OR, 7.09; 95% CI, 2.28–22.03; P = 0.001),
..
prevalence was significantly higher in fatal cases compared with survi- .. but not in patients with previous heart disease (P = 0.561,
vors (52% vs. 12%, P < 0.0001).31 In a cohort of 21 patients from the .. P = 0.337 and P = 0.992, respectively).44
..
USA admitted to an intensive care unit, 7 (33.3%) patients developed .. ARDS, hypoxaemia, acute kidney injury, hypervolemia, increased
dilated cardiomyopathy, characterized by globally decreased LV sys- .. adrenergic drive, stress-induced cardiomyopathy, fever, and a pro-
..
tolic function, clinical signs of CS, elevated creatine kinase, or tropo- .. found systemic inflammatory activation (‘cytokine storm’), character-
nin I levels, or hypoxaemia, without a history of systolic dysfunction.32 .. istic of severe infection and multiorgan dysfunction, could
..
An analysis of mortality causes in COVID-19 patients (150 hospital- .. also contribute to acute HF or exacerbation of chronic HF in
ized/68 dead) revealed that myocardial damage/HF and combined re- .. COVID-19.45
..
spiratory failure/myocardial damage/HF were responsible for 7% and .. Sustained/repetitive cardiac arrhythmia may also lead to deterior-
33% of fatal cases, respectively.33 These early reports require cau- .. ation in cardiac function. Apparently, cardiac arrhythmias have been
..
tious interpretation, because small sample size and inclusion of the .. described in 16.7% of all hospitalized COVID-19 patients and in
more severe cases may have resulted in an overestimation.
.. 44.4% of those requiring intensive care admission,41 and atrial
..
Recently, a meta-analysis of 30 studies (6389 patients) published .. tachyarrhythmias have been identified as a predictor of acute HF de-
..
between February and April 2020 including a broader spectrum of .. velopment.30 An ECG on admission should always be performed and
COVID-19 patients demonstrated that acute myocardial injury and .. serial ECGs are required in patients with myocardial injury and those
overt HF occur in 15.7% and 11.5% of patients, respectively.34 In a co-
..
.. receiving pro-arrhythmic drugs.
hort of 3080 confirmed cases in Spain, acute HF developed more fre- ..
quently in those with a history of chronic HF; however, 2.5%
..
.. Management of heart failure in
developed incident HF during SARS-CoV-2 infection.30 Similar results ..
.. individuals without COVID-19 during the
were reported in an Italian multicentre study.35 In addition to chronic ..
HF, advancing age, atrial tachyarrhythmias, and chronic obstructive .. COVID-19 outbreak
.. Internationally, several reports have suggested a decline in hospital-
pulmonary disease (COPD) were identified as independent predic- ..
tors of acute HF. Patients developing HF have significantly higher 30- .. ization rates for acute HF in individuals without SARS-CoV-2 infec-
.. tion during the peak of the COVID-19 pandemic compared with
day mortality rates compared to those without HF (46.8% vs. 19.7%, ..
P < 0.001), and withdrawal of standard HF medications increased in- .. 2019.46–48 Despite similar disposition and management, patients
.. admitted for acute HF in 2020 had more severe symptoms (e.g. New
hospital mortality.30 Recent studies show that COVID-19 also con- ..
fers greater risk of right ventricular dysfunction and dilation, which .. York Heart Association class III–IV in 96% vs. 77%, P = 0.03)49 and
.. higher in-hospital mortality (7.3% vs. 6.1%, P = 0.03) compared with
are predictors of poorer outcome.36 In a cohort of 510 COVID-19 ..
in-patients undergoing echocardiographic examinations, right ven- .. 2019.50 Also, a decline in the emergency department (ED) visits and
.. an increase in out-of-hospital CV mortality have been reported.51,52
tricular remodelling was associated with a more than two-fold in- ..
crease in mortality risk after adjustment for clinical variables and .. These findings call for further research into the causes and long-term
.. prognostic implications to inform strategic plans for the management
biomarkers.37,38 ..
There are several, not mutually exclusive, mechanisms of acute HF .. of chronic CV disorders during the COVID-19 crisis.
..
in COVID-19, such as: ..
acute myocardial injury (defined as serum high-sensitivity tropo-
..
.. Myocarditis
nin I elevation >99th percentile of the upper normal limit or new ..
abnormalities in electrocardiography or echocardiography) occurs
..
.
in 8–15% of COVID-19 patients.39 It may be caused by ischaemia, .. Key points
infarction, or inflammation (myocarditis). In patients with severe in-
..
.. • Acute myocarditis as traditionally defined by viral presence,
fection, evidence of acute myocardial injury is present in 22.2– .. inflammatory infiltrates, and myocardial injury is seldom
31%.31,40,41 A meta-analysis of four studies (n = 341) suggested that
.. demonstrated in COVID-19 patients with increased
..
in patients with severe infection, high-sensitivity troponin I was sig- .. interstitial myocardial macrophages shown in most of the
.. cases.53
nificantly higher at admission (mean standardized difference .
10 C. Baigent et al.
• Accumulating clinical experience indicates that myocarditis .. echocardiography and chest CT scan can be used for further
.. assessment, as indicated. In all instances, attention should be
can occur in SARS-CoV-2-infected individuals, even without ..
pulmonary involvement, with various clinical presentations, .. given to the prevention of viral transmission to healthcare
including fulminant myocarditis.53 .. providers and contamination of the equipment.
• COVID-19 myocarditis should be suspected in patients
.. • Patients with chronic HF should closely follow protective
..
with acute-onset chest pain, ST-segment changes and/or T .. measures to prevent infection.
wave inversion, cardiac arrhythmias, acute HF, and .. • Ambulatory HF patients (with no cardiac emergencies)
haemodynamic instability. Mild/moderate LV dilatation, .. should refrain from hospital visits.
.. •
global/multi-segmental LV hypocontractility, increased LV .. Guideline-directed medical therapy [including angiotensin-
wall thickness (suggestive of oedema), moderately elevated .. converting enzyme inhibitor (ACEI), angiotensin receptor
cardiac troponin, and increased NT-proBNP, without .. blocker (ARB) or sacubitril/valsartan, beta-blockers,

significant coronary artery disease, are also suggestive of
.. mineralocorticoid receptor antagonists, and other
..
myocarditis. In particular, suspicion of COVID-19 .. guideline-directed medications) should be continued in
myocarditis should be raised in patients with rapidly .. chronic HF patients, irrespective of COVID-19.
worsening acute HF/CS, without pre-existing CV disorders .. • Telemedicine should be considered whenever possible to
and acute coronary syndrome.
..
.. provide medical advice and follow-up of ambulatory HF
• Cardiac magnetic resonance, if available, is the preferred .. patients.
method for the diagnosis of acute myocarditis. ..
• Endomyocardial biopsy is not recommended for the
..
..
routine assessment of patients suspected of having COVID- . ..
19 myocarditis and should be limited to cases of severe or .. Prevention of SARS-CoV-2 infection
refractory HF where histological findings may guide .. During the COVID-19 outbreak, patients with chronic HF should be
therapeutic choices.
..
.. advised to closely follow protective measures aimed at preventing
• No clear recommendation could be given regarding the .. disease transmission (e.g. self-isolation, social distancing, frequent
treatment of patients with COVID-19 myocarditis. MCS, ..
inotropes and/or vasopressors, and mechanical ventilation
.. hand washing, use of hand sanitisers, and wearing a face mask in public
.. spaces). HF outpatients should avoid routine, non-urgent hospital vis-
may be needed in severe cases. There is no compelling ..
evidence to support the use of immunomodulatory .. its. Implementing remote monitoring may be an alternative.
therapy, including corticosteroids and intravenous ..
immunoglobulins. However, corticosteroids are indicated
..
.. Diagnostic hints
when there is respiratory involvement and have been .. Routine clinical methods, ECG (arrhythmias, myocardial injury, myo-
administered to patients who then had favourable clinical ..
outcomes.53–56 Tocilizumab and favipiravir are currently .. carditis), and chest X-ray (cardiomegaly, COVID-19 pneumonia) can
..
being tested in a randomized trial.57 .. provide a diagnostic clue. Due to the relatively low sensitivity of chest
.. X-ray to detect COVID-19 pneumonia, patients with a high degree
.. of clinical suspicion (tachypnoea, hypoxaemia), but with ambiguous
..
.. chest X-ray findings, should be referred to chest CT,61 which has
Incidence, underlying mechanisms and risk factors of COVID-19 .. high sensitivity and specificity to diagnose COVID-19-related pul-
myocarditis are currently unclear. Endomyocardial biopsies have ..
.. monary disease. Laboratory findings, such as increased erythrocyte
shown cardiotropism, including direct cardiomyocyte infection by .. sedimentation rate, fibrinogen and C-reactive protein, and lymphocy-
SARS-CoV-2, a high degree of interstitial macrophages in a majority ..
.. topenia, may suggest COVID-19 pneumonia. Transthoracic echocar-
of the cases, and multifocal lymphocytic myocarditis in a minority.27,58 ..
However, the mechanisms responsible for myocardial injury and dys- .. diography is useful, not only to evaluate the pre-existing LV
.. dysfunction in HF but also to assess patients suspected of having
function remain insufficiently understood. The clinical features vary. ..
Some patients present with fever, dyspnoea, and acute-onset chest
.. SARS-CoV-2-associated worsening cardiac function and/or myocar-
.. ditis.62 Prudent use of bedside point-of-care or transthoracic echo-
pain but without haemodynamic instability. Deterioration to acute ..
HF, hypotension, and CS may also occur.53 In the most severe cases,
.. cardiography should be considered when the result of an
.. examination is expected to provide a diagnosis and modify therapy.
fulminant myocarditis with CS has been described.59,60 ..
..
.. Chronic heart failure treatment
..
Chronic heart failure .. SARS-CoV-2 utilizes the angiotensin-converting enzyme-2 (ACE2)
.. receptors for cell entry and some data indicate that ACEIs and ARBs
Key points ..
.. may up-regulate ACE2,63 thus hypothetically increasing susceptibility
.. to the infection.
• The risk of COVID-19 may be higher in chronic HF ..
patients due to the advanced age and presence of several .. However, there is no clinical evidence of an association between
comorbidities. .. ACEI/ARB treatment and the susceptibility to infection, or the clinical
• Chronic HF patients with COVID-19 have a significantly
..
.. course. A recent study of 111 hospitalized patients with COVID-19
higher risk of adverse outcomes. .. in France treated with ACEI/ARB for CV disorders (9% with HF) has
• In HF patients suspected of COVID-19, routine clinical ..
.. demonstrated no association between exposure to ACEI/ARB and
assessment, temperature measurement, ECG (arrhythmias, .. the rate of complications or mortality in a propensity score-adjusted
ST-T wave changes), chest X-ray (cardiomegaly, COVID-19 ..
pneumonia), and laboratory findings (elevated sedimentation .. analysis.64 Similarly, in a cohort of 965 patients with COVID-19 from
rate, fibrinogen and C-reactive protein, and lymphocytopenia)
.. Spain (21.8% on ACEI/ARB), treatment with ACEI/ARB had a neutral
..
can provide a diagnostic clue. Transthoracic .. effect on mortality (OR, 0.62; 95% CI, 0.17–2.26; P = 0.486), HF (OR,
1.37; 95% CI, 0.39–4.77; P = 0.622), and other complications.44 .. and a favourable clinical course of COVID-19. However,
Furthermore, available data do not support discontinuation of ACEI/
.. variable clinical outcomes in solid organ recipients in earlier
..
ARB in HF patients with COVID-19, as this may increase the risk of .. coronavirus outbreaks [SARS and Middle East respiratory
.. syndrome (MERS)]71,72 suggest that hospitalization, close
death.30 Hence, it could be recommended that HF patients continue ..
.. monitoring, and appropriate treatment of COVID-19 heart
all prescribed guideline-directed medications (including ACEI, ARB, transplant patients should be recommended.
..
or sacubitril/valsartan), irrespective of COVID-19.65 ..
COVID-19 patients may become hypotensive due to dehydration, ..
..
septic shock, and haemodynamic deterioration; hence adjustment of ..
HF medication doses should be considered. .. LVAD patients are fragile, and every measure should be used to
.. prevent viral transmission. Cautious monitoring and management of
..

Chronic heart failure and outcomes in COVID-19
.. anticoagulation therapy is advised because both COVID-19 and anti-
.. viral medications can affect anticoagulant dosing. If technically feasible,
Worse clinical outcomes have been reported among COVID-19 ..
patients with a history of chronic HF. Along with an older age,
.. assessment of LVAD function by telemonitoring is preferable.
.. General recommendations for all LVAD patients should also be
arrhythmias, dementia, ischaemic heart disease, diabetes, obesity, and ..
hypertension, chronic HF has been associated with a higher risk of
.. applied, regardless of COVID-19.
.. Data on the susceptibility to infection and the clinical course of
hospitalization [hazard ratio (HR), 1.6, 95% CI, 1.2–2.1] and mortality ..
(HR, 2.3, 95% CI, 1.6–3.2) among 2653 COVID-19 patients in Italy.66
.. COVID-19 in heart transplant recipients are sparse. According to a
.. systematic review of four studies (one from China73 and three from
Similarly, in 9148 COVID-19 patients from South Korea, a history of ..
.. the USA74–76) on COVID-19-positive heart transplant recipients
chronic HF conferred a 3.17 higher odds ratio (95% CI, 1.88–5.34) .. (n = 33), the presenting symptoms were similar to those of immuno-
for mortality.67 Among 692 patients admitted for COVID-19 in 13 ..
.. competent individuals, including fever (81.8%), cough (94.8%), dys-
Italian cardiology centres, a history of HF has been associated with an .. pnoea (75.8%), and gastrointestinal complaints (48.5%).77 The
increased risk of death (adjusted HR, 2.25, 95% CI, 1.26–4.02), and in- ..
.. majority of patients (81.8%) were hospitalized, while 24.2% required
hospital complications, including acute HF (33.3% vs. 5.1%, P < 0.001), ..
acute renal failure (28.1% vs. 12.9%, P < 0.001), sepsis (18.4% vs. 8.9%, .. mechanical ventilation. The treatment included modification of main-
.. tenance immunosuppressive therapy (75.8%) and variable
P = 0.006), and multiorgan failure (15.9% vs. 5.8%, P = 0.004). 35 In a ..
cohort of 6439 hospitalized COVID-19 patients from the USA, a his- .. approaches with high-dose glucocorticoids, immunoglobulins, fluro-
.. quinolone antibiotics, tocilizumab, hydroxychloroquine, and antiviral
tory of HF conferred a 3.66 higher odds ratio (95% CI, 2.56–5.16, ..
P < 0.001) for mechanical ventilation and a 1.88 higher odds ratio .. medications. Of note, the overall mortality rate was 24.2%, while the
.. recovered patients remained rejection free.77 Yet another report of
(95% CI, 1.27–2.78, P = 0.02) for death, regardless of LV ejection frac- ..
tion or the use of ACEI.68 .. 87 heart transplant recipients from China indicated that high-degree
.. adherence to preventive measures (see above) resulted in a low rate
..
Telemedicine and home drug delivery
.. of infection and transition to manifest illness.78
..
Given the restraints to the usual care and high morbidity and mortal- .
ity among HF patients contracting COVID-19, the more widespread
... Valvular heart disease
..
use of telemedicine should be encouraged to minimize the risk of in- ..
.. Key points
fection, and to ensure continuity of care and timely optimisation of ..
medical treatment. Successful use of this technology has been ..
.. • Patients with VHD (particularly those with associated left
reported in providing medical advice, treatment adjustment, and .. or right ventricular impairment, or pulmonary
follow-up of ambulatory HF patients during the COVID-19 out- .. hypertension) may be at particular risk during the COVID-
..
break.69,70 If feasible (and necessary), home delivery and mailing of .. 19 pandemic
standard HF drugs may be a viable option, if permitted by local regu- .. • Coordinated allocation of resources at hospital and
.. regional level is essential to sustain ICU capacity
lations/laws. ..
.. • Maintained function of the Heart Team is paramount, even
.. if face-to-face meetings are not feasible.
..
Left ventricular assist device and heart transplantation ..
..
Key points .. VHD mainly affects the elderly and the symptoms of disease progres-
.. sion (mainly dyspnoea) may mimic those of lung infection or infiltra-
..
• Due to the nature of the device, left ventricular assist .. tion. In addition, VHD may aggravate the course of COVID-19 and
device (LVAD) patients have greater susceptibility to the .. complicate haemodynamic management of the systemic inflamma-
infection, and strict preventive measure should be applied ..
.. tory response (cytokine storm),79 ARDS, and any superimposed bac-
to avoid it. .. terial septicaemia (observed in up to one third of ICU patients).40 In
• Owing to the state of iatrogenic immunosuppression, heart ..
transplant recipients may be at a higher risk of severe .. early COVID-19 case series, up to 40% of patients admitted to the
COVID-19 disease or prolonged viral shedding; hence, tight
.. ICU had pre-existing congestive HF.32 Excess mortality was reported
..
adherence to preventive measures should be advised to .. in patients with VHD who were contaminated with COVID-19.
avoid infection. .. Among 136 elderly patients (mean age 80 years) with severe VHD
• Limited data suggest that heart transplant recipients may ..
.. [54% with aortic stenosis (AS)], 84.6% were treated conservatively
have a similar presentation as immunocompetent individuals .. and mortality at 30 days was as high as 41.8%.80
Elective surgical and transcatheter interventions for VHD con-

.. or no symptoms, provided close follow-up is organized using tele-
..
sume significant healthcare resources and many, or all, depending on .. medicine and face-to-face consultation in case of worsening symp-
circumstances, may be inappropriate during the pandemic given the
.. toms. TAVI (or balloon aortic valvuloplasty91) may be considered in
..
immense pressure on acute and intensive care facilities. During the .. haemodynamically unstable patients (COVID-19 positive/negative).92
first pandemic peak in England, a drastic reduction in valve surgery
.. However, the potential benefits of valve intervention in a critically ill
..
was observed, ranging from 73–76% for surgical aortic valve replace- .. COVID-19-positive patient should be carefully weighed against the
..
ment (SAVR) to 84–85% for surgical mitral valve replacement. .. likelihood of futility given the >60% mortality of COVID-19-positive
Transcatheter aortic valve implantation (TAVI) was less affected with .. patients admitted to ICU.93
..
a reduction of 35% and 18% during the months of April and May .. All cases should be discussed by the Heart Team and indications
..

2020, respectively.81 for TAVI extended to intermediate94,95 and selected low-risk
..
Patients with severe VHD must remain under close telephone sur- .. patients.96,97 Increased use of transfemoral TAVI, when feasible, may
veillance and be encouraged to report progressive symptoms. .. allow optimal utilization of resources by avoiding general anaesthesia
..
Concentration of resources on the treatment of pandemic victims .. and intubation, shortening or preventing an ICU stay, and accelerat-
guides decisions with the overall aim of avoiding shortages of ICU .. ing hospital discharge and recovery.98
..
beds and ventilators. Prioritization of valve interventions should ..
therefore balance the immediate and short-term prognosis of individ- ..
ual patients against available resources and the risk to patients and ... Management of mitral regurgitation
..
HCP of acquiring in-hospital infection. In this respect, use of less-inva- ..
sive procedures (particularly TAVI via transfemoral approach per- .. Key points
..
formed under conscious sedation and/or local anaesthesia), may .. • The majority of patients with mitral regurgitation (MR) is
present an opportunity to minimize the need for healthcare resour- ..
.. stable and surgical or transcatheter intervention can be
ces, including ICU and hospital stays. The need for clinical decision- .. deferred.
making by Heart Teams remains of paramount importance and the
.. • Priority should be given to the treatment of patients with
..
use of telemedicine or other means of virtual communication is es- .. acute MR complicating, e.g. acute myocardial infarction
sential if face-to-face meetings are difficult, or impossible, during the
.. (AMI) or infective endocarditis (IE), and those with severe
.. symptomatic primary MR or secondary MR (SMR) that is
acute phase of the pandemic. .. not responsive to guideline-directed medical and device
..
.. treatment and seems likely to require hospital admission.
Management of aortic stenosis .. The choice of intervention should be guided by the Heart
.. Team.
..
Key points ..
.. The management of MR differs according to its aetiology and presen-
..
• Priority should be given to patients with syncope and HF, .. tation. Chronic primary MR (e.g. flail leaflet and Barlow disease) is
and those with high (or very high) transvalvular gradients .. usually stable and well tolerated. In contrast, SMR is a more variable
and/or impaired LV function.
..
.. entity and while many patients remain stable under guideline-
• Non-urgent procedures should be deferred based on .. directed medical and device treatment (including sacubitril/valsartan
objective criteria assessed by the Heart Team. ..
.. and cardiac resynchronization therapy when indicated),99 others may
• Greater use of transfemoral TAVI (as judged appropriate by
the Heart Team) may allow optimal utilization of healthcare ... develop unstable HF syndromes that are refractory to medical treat-
resources.
.. ment, particularly in the context of acute infection.100
..
.. In the context of the COVID-19 pandemic, priority should be
.. given to the treatment of patients with acute primary MR complicat-
..
The prognosis of patients with severe AS depends on several factors, .. ing, e.g. AMI or IE, and those with severe primary or SMR who remain
including age, symptomatic status, peak aortic jet velocity/mean trans- .. symptomatic despite guideline-directed medical and device treat-
..
valvular gradient,82,83 left ventricular ejection fraction, pulmonary .. ment and seem likely to require hospital admission. All other patients
hypertension,84 and elevated biomarkers (natriuretic peptides or .. should be managed conservatively.99–102
..
troponin).85–87 Mortality of patients with severe symptomatic AS .. Transcatheter mitral edge-to-edge repair may be considered in
who are treated conservatively is high, reaching 50% at 1 year and
.. anatomically suitable high-risk or inoperable patients with acute MR
..
70–80% at 2 years.88 Deferring SAVR or TAVI was associated with an .. (excluding those with IE) or highly selected patients with highly symp-
increased risk of hospitalization for valve-related symptoms or wor-
.. tomatic (NYHA III–IV or congestive HF) primary MR or SMR refrac-
..
sening HF (19.6% within the first month).89 In another study, 10% of .. tory to guideline-directed medical and device treatment. Despite a
patients awaiting an intervention died or required urgent TAVI.90
.. low risk of complications requiring ICU admission,103 the procedure
..
In the context of the COVID-19 pandemic, the Heart Team should .. requires general anaesthesia (in distinction to transfemoral TAVI)
undertake systematic individual risk assessment based on objective
..
.. and prolonged transoesophageal echocardiographic guidance, there-
criteria that determine disease progression. Priority should be given .. by exposing echocardiographers and anaesthetists to the risk of
..
to patients with syncope or HF [New York Heart Association .. COVID-19 transmission. Use of temporary circulatory support
(NYHA) Class III/IV], high or very high transvalvular gradients, and .. (intra-aortic balloon pump or Impella) should be restricted to
..
those with reduced LV function (See Guidance Part 1), whereas a .. patients with a good prospect of recovery in the context of available
watchful waiting strategy is more appropriate in those with minimal .. ICU resources.
..
Hypertension .. expected in older patients with severe infection. Moreover, obesity
.. and diabetes are significant risk factors for poorer outcomes in
..
Key points .. patients with COVID-19 and hypertension commonly co-segregates
.. with these comorbidities. New evidence from a very large study
..
• The early reports of an association between hypertension .. involving over 20 million people and 10 000 COVID-19 deaths
and risk of severe complications or death from COVID-19 .. showed no independent association between hypertension and risk
..
were confounded by the lack of adjustment for age and .. of death from COVID-19.107
high-risk comorbidities such as obesity and diabetes that .. It now seems likely that the reported association between hyper-
commonly co-segregate with hypertension. There is ..
currently no evidence to suggest that hypertension, per se,
.. tension and risk of severe complications or death from COVID-19 is
..

is an independent risk factor for severe complications or .. substantially confounded by the lack of adjustment for age and other
death from COVID-19. .. unmeasured confounders.108 There is currently no evidence to sug-
• Despite much early speculation of a link between use of .. gest that hypertension, per se, is an independent risk factor for severe
..
ACEIs or ARBs and increased risk from COVID-19, .. complications or death from COVID-19.
evidence from a series of observational cohort studies from ..
across the world published in major journals has shown ..
that prior or current treatment with ACEIs or ARBs does ..
.. Antihypertensive treatment with angiotensin-converting
not increase the risk of COVID-19, or the risk of ..
developing severe complications or death from COVID-19, .. enzyme inhibitors or angiotensin receptor blockers
when compared to the risk in patients taking other ..
.. Renin–angiotensin system (RAS) blockade with ACEIs or ARBs is the
antihypertensive drugs. .. foundation of antihypertensive therapy in the current ESC–ESH
• Two randomized controlled trials have been published ..
Guidelines for the management of arterial hypertension (2018).109
(REPLACE COVID) (BRACE-CORONA), both addressing ... The recommended treatment of hypertension for most patients is a
whether ACEIs or ARBS should be continued or withdrawn ..
in patients admitted to hospital with COVID-19. In both .. combination of an ACEI or ARB with a calcium channel blocker
studies, there was no difference in major outcomes from .. (CCB) or thiazide/thiazide-like diuretic.109
COVID-19 whether or not the patients were randomized
..
.. Early in the pandemic, concern had been expressed that treatment
to continue or discontinue their treatment with ACEIs or ..
ARBs. .. with ACEIs or ARBs might increase the risk of infection, or of devel-
• Treatment of hypertension should follow existing
.. oping the severe consequences of infection with COVID-19.110–112
..
recommendations in the ESC-European Society of .. This concern originated from a hypothesis linking the observations
Hypertension (ESH) Guidelines. No change to these .. that COVID-19 invades cells by binding to the enzyme ACE2, which
treatment recommendations is necessary during the ..
COVID-19 pandemic.
.. is ubiquitous and expressed on the surface of alveolar cells in the
.. lung.113–115 In some animal studies, but not all, ACEIs or ARBs have
• Self-isolated patients with treated hypertension should not ..
need to attend hospital for routine review visits during this .. been shown to increase ACE2 levels, mainly in cardiac tissue.116–118
pandemic. Patients could make use of periodic home blood
.. There are no studies showing that RAS-blocking drugs increase
..
pressure (BP) monitoring, with videoconference or phone .. ACE2 levels in human tissues and no studies in animals or humans
consultations only if needed (Figure 4). .. showing that RAS-blocking drugs increase ACE2 levels in the lung, or
• Hypertensive patients may be at increased risk of cardiac ..
.. that the level of ACE2 expression in the lung is rate limiting for
arrhythmias due to underlying cardiac disease, or the ..
reported higher frequency of hypokalaemia in patients with .. COVID-19. A recent study of human tissues indicates that neither
severe COVID-19. .. hypertension nor antihypertensive treatment (including ACEI or
• .. ARBs) altered the expression of ACE2 in the human kidney but did
Antihypertensive therapy may need to be temporarily ..
withdrawn in acutely ill patients in hospital who develop .. show that ACE2 expression was increased in both lungs and kidneys
hypotension or acute kidney injury secondary to severe .. with ageing, which may be relevant to the striking increased risk of
COVID-19.
..
.. Covid-19 with ageing in SARS-CoV-2 infection.119
• In patients previously treated for hypertension who require ..
...
invasive ventilation, parenteral antihypertensive medication Series of observational cohort studies have been published in
is only indicated for those developing persistent severe .. major journals which consistently show that treatment with RAS
hypertension. .. blockers does not increase the risk of COVID-19 or increase the risk
.. of severe complications or death from COVID-19.120–125 In one
..
.. study, there was even a substantial reduction in the risk of severe
..
.. complications or death from COVID-19 in patients with diabetes
Hypertension and COVID-19 .. mellitus.121
Initial reports from China noted that hypertension was one of the
..
.. Two randomized controlled trials addressing concerns about
most common co-morbidities (20–30% of cases) associated with the .. ACEI and ARBs in patients hospitalized with COVID-19 have now
need for ventilatory support due to severe respiratory complications
..
.. been published. The first study (BRACE CORONA) showed that in
of COVID-19.40,41,104–106 These analyses did not adjust for age, which .. 659 patients from 29 sites in Brazil admitted to hospital with COVID-
is important because hypertension is very common in older people
..
.. 19 and currently treated with ACEIs or ARBs, there was no differ-
(50% in people over 60 are hypertensive) and hypertension preva- .. ence in outcomes (days alive and out of hospital at 30 days), whether
..
lence increases sharply in the very old. Older age is by far the most .. or not the patients were randomized to continue or discontinue their
important risk factor for severe complications and death due to .. treatment with ACEIs or ARBs.126 In the second randomized con-
..
COVID-19; thus, a high frequency of hypertension would be . trolled trial (REPLACE COVID), 152 participants were randomly
Self-isolated hypertensive patient
Continue treatment with antihypertensive medication according to

ESC-ESH guidelines 2018
No need to adjust medication or stop ACE-inhibitors or ARBs
because of COVID-19 pandemic

Continue to monitor blood pressure at home, if possible
No need for routine clinical review at clinical during the COVID-19
pandemic
Use video or phone consulation with patient, if required
Hospitalized hypertensive patient with COVID-19 infection
Unless hypotensive or there is acute kidney injury

Continue treatment with antihypertensive medication according to
ESC-ESH guidelines 2018
No need to adjust medication or stop ACE-inhibitors or ARBs
because of COVID-19 pandemic
Monitor for arrhythmias which may be more common in hypertensive

patients with cardiac disease
Check plasma potassium, as hypokalaemia is common in hospitalized
COVID-19 patients
Parenteral antihypertensive medications will only rarely be necessary
in ventilated patients
Figure 4 Hypertension management in the COVID-19 context. ACE, angiotensin-converting enzyme; ARBs, angiotensin II receptor blockers;
COVID-19, coronavirus disease 2019.
..
assigned to either continue or discontinue renin–angiotensin system .. reason why these drugs should be discontinued due to concern
inhibitor therapy and, irrespective of randomized group, there was .. about COVID-19. Treatment of hypertension, when indicated,
..
no difference in a global rank score of major outcomes.127 .. should continue to follow the existing ESC–ESH guideline
This series of large-scale observational studies and the first .. recommendations.134
..
randomized controlled trials provide a consistent message and re- ..
assurance to patients and their doctors that the prior speculation
..
..
about the safety of RAS blockers in the context of COVID-19 has .. Remote management of hypertension in the patient
not been proven.128
..
.. isolated at home
Indeed, studies in animal models of infection with influenza or .. Most patients with hypertension require only infrequent visits to the
coronaviruses have suggested that ACE2 is important in protecting
..
.. clinic to manage their hypertension. Many patients with treated
the lung against severe injury and that RAS-blocking drugs are also .. hypertension will be in self isolation to reduce the risk of COVID-19
protective against severe lung injury due to these viruses.129–131
..
.. and unable to attend their usual routine clinical review. When pos-
Human studies of RAS blockade or recombinant ACE2 to prevent .. sible, patients should monitor their own BP as frequently as they usu-
..
respiratory decompensation in COVID-19-infected patients have .. ally would, using a validated home BP monitor.109
been suggested, planned, or are ongoing.132,133 .. Videoconference or telephone consultation with patients, when
..
In summary, there is currently no evidence to suggest that ACEIs .. required, may facilitate urgent physician follow-up until normal clinic
or ARBs increase the risk associated with COVID-19 and there is no .. attendance resumes.
..
Hypertension and the hospitalized patient .. for all patients admitted to the hospital with COVID-19. It has been
with COVID-19 .. argued that more intensive anticoagulation [such as low molecular
..
Most patients who are hospitalized will have more severe infection .. weight heparin (LMWH) at intermediate dose or even full
and be hospitalized for respiratory support. They are likely to be .. therapeutic-dose anticoagulation] may be indicated in critically ill
..
older with comorbidities, such as hypertension, diabetes, and chronic .. patients with COVID-19 pneumonia, but such a practice is not sup-
kidney disease. Patients with severe disease may also develop multi- .. ported by current evidence. In fact, it remains unknown whether
..
organ complications in severe disease. .. bleeding rates on more intensive anticoagulation can be acceptably
Hypertensive patients may also have LV hypertrophy or heart dis- .. low, or if they outweigh the potential prevention of more thrombotic
..
ease and be at increased risk of developing arrhythmias, particularly .. complications. Of note, patients with COVID-19 pneumonia have
..

when hypoxic.135 Plasma potassium levels should be monitored be- .. been shown to develop acute PE even when they were on full-dose
cause arrhythmias may be exacerbated by the frequent occurrence .. anticoagulation.137–143
of low plasma potassium levels, which appears to be more prominent .. Patients with COVID-19 often present with respiratory symptoms
..
in hospitalized COVID-19-infected patients with more severe dis- .. and may also report chest pain and haemoptysis.104 These symptoms
ease.136 This is thought to be due to increased urinary loss of potas-
.. largely overlap with the presentation of acute PE, and this fact may re-
..
sium, which may be exacerbated by diuretic therapy. .. sult in underdiagnosis of this relevant complication.147 Unexpected
If patients are acutely unwell and become hypotensive or develop
.. respiratory worsening, new/unexplained tachycardia, a fall in BP
..
acute kidney injury due to their severe disease, antihypertensive ther- .. not attributable to tachyarrhythmia, hypovolaemia, or sepsis
apy may need to be withdrawn. Conversely, parenteral antihyperten-
.. (new-onset), ECG changes suggestive of PE, and signs of deep vein
..
sive drugs are rarely needed for hypertensive patients who are .. thrombosis of the extremities should trigger a suspicion of PE. It is
ventilated and have sustained any significant increases in BP after
.. recommended to order diagnostic tests for PE only when it is clinical-
..
withdrawal of their usual treatment (i.e. grade 2 hypertension, BP .. ly suspected, although the threshold of suspicion should be kept low.
..
>160/100 mmHg), but the objective in these acute situations is to .. The specificity of D-dimer tests may be lower in patients with
maintain BP below these levels and not aim for optimal BP control. .. COVID-19 compared to other clinical settings. Even so, it is still
..
.. advised to follow diagnostic algorithms starting with pre-test prob-
.. ability and D-dimer testing, especially when pre-test probability-de-
..
Acute pulmonary embolism—prevention .. pendent D-dimer thresholds are being used.148–150 This may help to
and diagnosis .. rationalize the deployment of resources and personnel for transport-
..
.. ing a patient to the radiology department with all the associated isola-
.. tion precautions. In the clinical scenario of a patient with COVID
Key points ..
.. who has just undergone computed tomography (CT) of the lungs but
• Prescribe anticoagulation at standard prophylactic doses in .. the findings cannot explain the severity of respiratory failure, CT pul-
..
all patients admitted with COVID-19. .. monary angiography should be considered before leaving the radi-
• Consider the presence of acute pulmonary embolism (PE) .. ology department.
in patients with COVID-19 in the setting of unexpected ..
respiratory worsening, new/unexplained tachycardia, a fall
.. When acute PE is confirmed, treatment should be guided by risk
.. stratification in accordance with the current ESC guidelines.151
in BP not attributable to tachyarrhythmia, hypovolaemia or ..
sepsis, (new-onset) ECG changes suggestive of PE, and signs .. Patients in shock should receive immediate reperfusion therapy.
of deep vein thrombosis of the extremities. ... Haemodynamically stable patients should be treated with unfractio-
• When acute PE is confirmed, treatment should be guided .. nated heparin (UFH), LMWH, or a non-vitamin K antagonist oral
by risk stratification in accordance with the current ESC
..
.. anticoagulant (NOAC), depending on the feasibility of oral treat-
guidelines. .. ment, renal function, and other circumstances. When choosing the
..
.. appropriate drug and regimen (parenteral vs. oral) for initial, in-
.. hospital anticoagulation, the possibility of rapid cardiorespiratory or
Observational studies in China, Europe, and the USA have reported ..
a high incidence of thrombotic and thromboembolic complications in .. renal deterioration due to COVID-19 should be taken into account.
..
patients with COVID-19 pneumonia.137–143 The wide range of .. Acute renal deterioration or failure precludes continuation of (the
described incidence rates is mostly caused by detection bias with .. same dose of) NOACs and should therefore be closely monitored.
..
variable thresholds for diagnostic testing and, occasionally, limited .. Because of the need for anticoagulation monitoring, which may con-
availability of radiological tests. Most of the studies have demon- .. tribute to spreading of the infection, vitamin K antagonists should
..
strated that acute PE is the most frequent thrombotic complica- .. only be considered in special clinical settings, such as the presence of
tion.137–143 It is debateable whether the contrast-filling defects seen .. mechanical prosthetic valves or the antiphospholipid syndrome.151
..
on computed tomography pulmonary angiography represent ‘con- .. Of note, several studies have described a high prevalence of antiphos-
ventional’ venous thromboembolism (VTE), or if they are induced by .. pholipid antibodies in patients with COVID-19.152–154 The clinical
..
in situ immunothrombosis involving, among others, neutrophil extra- .. relevance and implications of this finding are, at present, unknown.
cellular traps.144–146 Likely, VTE and immunothrombosis both con- .. Antiphospholipid antibodies are common during infections. Whether
..
tribute to the high incidence of PE in severe COVID-19 pneumonia. .. the type and titre of the antiphospholipid antibodies described in
Therefore, in view of COVID-19-associated local and systemic in-
.. COVID-19 patients, i.e. IgA isotype alone and low titres, may pro-
..
flammation, coagulation activation, hypoxaemia, and immobilization, .. voke thrombotic complications remains controversial. Based on cur-
anticoagulation at standard prophylactic doses should be considered
.. rent evidence, routine screening for antiphospholipid antibodies in
patients with COVID-19 cannot be recommended. However, if triple .. The general principles of management of patients with cardiac
..
positivity for antiphospholipid antibodies is demonstrated, i.e. lupus .. arrhythmias and cardiac implantable devices during the COVID-19
anticoagulant, positive anti-beta-2-glycoprotein antibodies, and posi-
.. pandemic are based on:
..
tive anti-cardiolipin antibodies, in patients with proven venous or ar- ..
.. • Continuing to provide emergency high-quality care safely to all
terial thrombosis, NOACs should be avoided. .. patients with life-threatening cardiac arrhythmias and implantable
.. devices.
..
.. • Preserving healthcare resources to allow the appropriate treat-
Arrhythmias .. ment of all patients with COVID-19.
.. • Minimizing the risk of nosocomial infection of non-infected
..
..

Key points .. patients and healthcare workers.
.. Several national and international societies and health services
• For monitoring and follow-up of patients with cardiac .. including the Heart Rhythm Society, National Health Service (UK)
implantable devices, remote monitoring should be utilized ..
as much as possible. .. and the Cardiac Society of Australia and New Zealand have issued
.. similar local recommendations to achieve these goals and guide the
• When healthcare resources are scarce, elective ablation ..
and cardiac device implantation procedures should be .. management of patients with cardiac arrhythmias and cardiac
postponed and urgent procedures should only be .. implantable devices during the COVID-19 pandemic.155–158
performed after careful consideration of all pharmacological
..
..
treatment options. ..
• In hospitalized patients with COVID-19, arrhythmias, .. Monitoring and follow-up of patients with cardiac
especially new-onset or recurrent atrial fibrillation (AF) and
.. implantable devices
..
atrial flutter (AFL), occur frequently. Occurrence of .. Transition to remote interrogation (patient-initiated or automatic
significant arrhythmias is a marker of COVID-19 severity .. prescheduled transmissions) or remote monitoring (i.e. automatic
and is associated with higher mortality. ..
• .. daily or alert-triggered transmissions) of cardiac implantable elec-
When treating arrhythmias, drug–drug interactions, .. tronic devices (CIEDs) during the COVID-19 pandemic was proven
including antiviral, antiarrhythmic, and anticoagulation ..
therapies, should be considered before co-administration. .. feasible in a small single-centre Italian study159 and has been reviewed
• In critically ill patients with hemodynamic instability due to
.. in detail in a recent worldwide document.158
..
recurrent ventricular tachycardia (VT)/ventricular .. • Remote interrogation and monitoring should be utilized as much
fibrillation (VF) or AF/AFL, intravenous (i.v.) amiodarone is ..
the choice for antiarrhythmic medication. .. as possible to replace routine device interrogation visits to hospi-
•
.. tals, clinics and practices. In-person office visits should be replaced
Therapy of TdP VT consists of withdrawal of all QT ..
prolonging drugs, targeting Kþ >_ 4.5 mEq/L, i.v. magnesium .. by remote contact by telephone or internet by the treating phys-
supplementation and increasing heart rate (by withdrawing .. ician, using the device information obtained through remote inter-
bradycardic agents and if needed by i.v. isoproterenol or
..
.. rogation or monitoring.
temporary pacing); i.v. lidocaine or oral mexiletine may be .. • For patients who are followed already through remote interroga-
considered for the treatment of refractory cases based on .. tion/monitoring, deferring in-office evaluation is usually possible.
limited clinical data. ..
•
.. This may have psychological implications, as patients may feel that
New-onset primary malignant ventricular arrhythmia and .. a delay of their regular check-up may prejudice the integrity of
sudden arrhythmic death seem to be relatively rare in ..
COVID-19. In critically ill patients, malignant ventricular .. their device. Reassurance on these issues therefore is important
arrhythmias are a marker of disease severity and occur
.. when patients are called to postpone their visit.
.. • For patients not already followed via remote interrogation/moni-
more frequently, especially in the terminal phase of the ..
disease. .. toring, activation requires registering the transmitter, obtaining
• New-onset malignant ventricular tachyarrhythmia or severe .. consent from the patient, and activating the feature in some cases.
..
bradyarrhythmia not explained by end-stage respiratory .. Initiating remote interrogation/monitoring without the patient
failure may be a marker of acute myocardial injury and .. coming to the office or hospital may be an option for Boston
should trigger diagnostic cardiac evaluation. Ischaemia and .. Scientific and Abbott devices [pacemaker (PM) and ICD] and for
hypoxaemia should be excluded, and inflammation and
..
.. newer Medtronic devices using BlueSync, since remote monitoring
cardiac biomarkers should be followed. Echocardiography .. is programmed ON as default on these CIEDs. Legacy Medtronic
should be considered to assess ventricular function and ..
.. devices can be initiated at home by the patient for remote interro-
myocardial involvement. In case myocarditis is suspected,
magnetic resonance imaging (MRI) may be considered (see ... gation, but alert-based monitoring of non-BlueSync Medtronic
Guidance Part 1), as the diagnosis may warrant more .. ICDs requires an in-office programming ON. Also, for Biotronik
aggressive immunosuppressive and antiviral treatment.
.. CIEDs, remote monitoring needs an in-office programming ON of
..
• After recovery from the COVID-19, in AF/AFL the .. the CIED, unless that has been done at the time of implant, as is
therapeutic choices of rate and rhythm control should be .. customary in some countries and centres. When the CIED is
re-assessed, and long-term anticoagulation should be
.. ready, for all manufacturers the patient only needs to plug in the
..
continued based on the CHA2DS2-VASc score. The need .. transmitter device at home, which then activates automatically
for permanent pacing in bradycardia and for catheter .. (Biotronik; Abbott) after a single push of a button (Boston
ablation, secondary prophylactic implantable cardiac ..
defibrillator (ICD) or wearable defibrillator in ventricular
.. Scientific or BlueSync Medtronic), or after a series of actions
.. with a removable wand (legacy Medtronic) that can be guided
tachyarrhythmia needs to be re-evaluated. .. over the phone. Manufacturers point to the restrictions by privacy
..
regulation (like General Data Protection Regulation) to directly .. in 13%, VT or VF in 2.6% (1.9% sustained VT or VF), and atrioven-
send transmitters to the patient’s home and should provide devi- .. tricular (AV) block in 0.4% of the patients. Age, male sex, and hypoxia
ces to the hospital from where they may be shipped to the
..
.. on presentation were independently associated with occurrence of
patient. .. arrhythmias. The presence of arrhythmias correlated with disease se-
• Remote interrogation/monitoring may require hospital re-organ- ..
.. verity, elevated markers of myocardial injury, inflammation, and fi-
ization, which can preclude large-scale transitioning from an .. brinolysis and was independently associated with 30-day mortality.
outpatient setting to a telemetry-based model during hectic ..
COVID-19 times when hospital operations are already stretched. .. Very similar results were recently reported in a large multicentre
.. Italian study with 21.7% incidence of sustained tachyarrhythmias in
• Device patients for whom a scheduled in-office visit needs to be ..
postponed can also be reassured that major alterations of device .. 414 hospitalized patients.161 Based on these studies, it seems that
.. tachyarrhythmias are a marker of COVID-19 severity occurring

integrity will be signalled by an auditory alarm. Patients should be ..
instructed to contact their centre if they notice such an alarm. .. more frequently in patients with more severe disease and are associ-
• Patients without new symptoms or alarms should be rescheduled .. ated with higher mortality.
..
for device follow-up after the pandemic. .. In general, the acute treatment of arrhythmias should not be signifi-
• Urgent in-hospital or ambulatory device interrogations may be .. cantly different from their management in non-COVID-19 patients
needed for patients with suspected new and severe lead dysfunc-
..
.. and should be in line with the current ESC, European Heart Rhythm
tion; battery depletion, especially in PM-dependent patients; malig- .. Association and related guidelines.162–168
nant arrhythmia detection; appropriate or inappropriate ICD ..
..
therapy delivery if this cannot be sufficiently managed by remote .. Tachyarrhythmias
interrogation/monitoring. ..
• All patients should be screened for symptoms or exposure to
..
.. Supraventricular tachycardia. In an Italian multicentre study of 414 hos-
confirmed COVID-19 prior to admission: .. pitalized patients, the incidence of non-AF/AFL type of supraventricu-
• In patients without suspected or confirmed COVID-19 ..
• Preferably, interrogation should use wireless communi-
.. lar tachycardia (SVT) was 1.2%.161 In theory, exacerbation of known
.. SVT or new-onset SVT may occur in patients with COVID-19.
cation to minimize direct contact while maintaining a ..
safe distance and using appropriate personal protective
.. Special considerations during the COVID-19 pandemic are necessary
.. in a resource-constrained environment considering the transient un-
equipment (PPE). ..
• Interrogation should be performed in separate designated .. availability of catheter ablation procedures for definitive treatment,
.. the risk of nosocomial infection during repeated ED visits, and the
non-infected areas (see Supplementary material online, ..
Section 1). .. possibility of therapy interactions with antiarrhythmic drugs (AADs)
• In patients with suspected or confirmed COVID-19: Local hos- .. (see Section Treatment of severe acute respiratory syndrome cor-
..
pital protocols for the use of a dedicated single set of pro- .. onavirus 2 infection).
grammers with appropriate storage in designated areas, ..
.. • Intravenous adenosine can probably be used safely for acute ter-
cleaning before and after use, single use wand protection and .. mination, but confirmatory data are lacking
the use of appropriate PPE (see Supplementary material online, ..
Section 1) are recommended. Preferably, interrogation should
.. • Maintenance therapy with beta-blockers (or CCBs if beta-blockers
.. are contraindicated) should be initiated with a low threshold.
use wireless communication, obviating direct contact. ..
.. Drug interaction with antiviral drugs should be evaluated, including
.. the avoidance of bradycardia to avoid excessive QT prolongation
.. (see the Treatment of severe acute respiratory syndrome corona-
Considerations for electrophysiological and implantable ..
device procedures
.. virus 2 infection)
.. • After the COVID-19 pandemic, the indication for catheter ablation
The categorization of electrophysiology procedures in the context of ..
COVID-19 is depicted in Table 3.
.. should be reassessed.
..
.. Atrial fibrillation and flutter. AF/AFL occur in 15–20% of patients hos-
..
Management of cardiac arrhythmias in patients with .. pitalized with COVID-19.160,161,169–173 New-onset AF occurs in
.. around 10% of the patients, accounting for up to 60% of COVID-19
COVID-19 ..
The incidence and type of cardiac arrhythmias in patients with .. patients with AF.169,171,172 The incidence of AF is higher, reaching up
.. to 40% in critically ill COVID-19 patients.169,171–173 Specific precipi-
COVID-19 depends on the patient population studied, the intensity ..
of monitoring, the definition of arrhythmias, and the length of follow- .. tating factors in this setting are hypokalaemia and hypomagnesemia
..
up. In an initial single-centre retrospective study including 138 hospi- .. (induced by nausea, anorexia, diarrhoea, and medications), metabolic
talized patients in Wuhan, China, cardiac arrhythmias occurred in .. acidosis, the use of inotropic agents (especially dobutamine and
..
16.7% of patients. Arrhythmias occurred more frequently in patients .. dopamine), ventilator dyssynchrony, volume overload, increased
who were transferred to the ICU (44% vs. 6.9%, P < 0.001, respect- .. sympathetic tone, inflammation, hypoxia, ischaemia, bacterial super-
..
ively).41 However, the type and duration of arrhythmias were not .. infection, and acute myocardial injury.162 Age, male sex, prior AF,
specified in this report. In a more recent large study of 1053 hospital- .. renal disease, and hypoxia on presentation have been independently
..
ized patients followed for a median of 7 days on telemetry, arrhyth- .. associated with the occurrence of AF.172 The incidence of AF in
mia was reported in 25.6% of patients.160 AF was the most frequent
.. COVID-19 is similar to other aetiologies of severe pneumonia,
..
arrhythmia occurring in 15.8% of patients, with 9.6% being newly .. ARDS, and sepsis. Reportedly, 23–33% of critically ill patients with
diagnosed, followed by frequent premature ventricular contractions
.. sepsis or ARDS have AF recurrence and 10% develop new-onset
Table 3 Categorization of electrophysiological procedures in the context of COVID-19
Urgent (perform within Lower priority (perform Elective (may be postponed Personal
days) within <3 months) 3 months) protection
level
....................................................................................................................................................................................................................
Catheter ablation • VT/VF ablation for electrical • VT ablation for medically refrac- • PVC ablation II/III
storm tory recurrent VT • PSVT ablation
• AF or A flutter ablation for • AF/A flutter ablation for medic- • AF/A flutter ablation
AF/A flutter causing tachycar- ally refractory AF/A flutter with • EP testing

diomyopathy or syncope repeated ER visits
• WPW syndrome with fast • Medically refractory SVT with
preexcited AF and or syncope repeated ER visits
and/or cardiac arrest
Cardiac implantable • Urgent PM implantation for • ICD/PM battery replacement for • Primary prevention ICD II/III
electronic device symptomatic high-degree AV ERI • CRT implantation
block or sinus node dysfunc- • Primary prevention ICD in very • CIED upgrade
tion with long asystolic pauses high-risk or life-threatening ven- • Lead extraction in patient
• Urgent secondary prevention tricular arrhythmias without infection
ICD implantation for cardiac • Lead revision for asymptomat-
arrest or VT ic malfunction
• ICD/PM battery replacement
for imminent or actual EOL in
PM-dependent patients
• Lead revision for symptomatic
malfunction
• Lead extraction for infection
Cardioversion/other • Highly symptomatic medically • Symptomatic medically refrac- • LAA closure II/III
EP procedures refractory new onset of AF/A tory AF/A flutter • ILR implantation
flutter • Tilt table testing
• Ambulatory rhythm
monitoring
A, atrial; AF, atrial fibrillation; AV, atrioventricular; CIED, cardiac implantable electronic device; CRT, cardiac resynchronization therapy; EOL, end of life; EP, electrophysiology;
ER, emergency room; ERI, elective replacement indicator; ICD, implantable cardioverter–defibrillator; ILR, implantable loop recorder; LAA, left atrial appendage; PM, pace-
maker; PSVT, paroxysmal supraventricular tachycardia; PVC, premature ventricular contraction; SVT, supraventricular tachycardia; VF, ventricular fibrillation; VT, ventricular
tachycardia; WPW, Wolff–Parkinson–White syndrome.
AF.162,174–176 New-onset AF in sepsis and ARDS has been associated

.. however, needs to be balanced vs. the need for more equip-
..
with higher short- and long-term mortality, very high long-term re- .. ment and personnel at the side of the patient, and the possible
currence rate, and increased risk of HF and stroke.162,174–176
.. need for intubation (with the risk of increased viral aerosol
..
Similarly, in COVID-19, AF has been independently associated in one .. creation).
.. • In critically ill patients with haemodynamic instability due to new-
large US study with significantly higher 30-day mortality (39.2% com- .. onset AF/AFL, IV amiodarone is the choice for antiarrhythmic
pared to 13.4% of patients without AF, P < 0.001).172 In this study, 6% ..
.. medication for rate and rhythm control. Its combination with
of patients with AF/AFL experienced stroke or TIA during their hos- .. hydroxychloroquine and/or azithromycin should be avoided, pref-
pitalization, 20% of them while under therapeutic anticoagulation.172 ..
.. erably (see Section Treatment of SARS-CoV-2 infection).
Long-term AF recurrence rate, HF, and mortality risks following re- .. Amiodarone may also interfere with cellular SARS-CoV-2 entry
covery from COVID-19 and AF are unknown but are expected to be .. and amplification and is being investigated in a study as a candidate
..
significant. .. antiviral drug in the early stage of the disease.177
As in all patients with AF, treatment goals have to consider ven- .. • In patients with severe acute respiratory insufficiency, cardiover-
..
tricular rate control, rhythm control, and thromboembolic prophy- .. sion is unlikely to provide sustained benefit without concomitant
laxis. Specifically, in the context of COVID-19, the following .. intensified treatment of the underlying hypoxaemia, inflammation,
.. and other reversible triggers, such as hypokalaemia and hypomag-
considerations should be made (Figure 5): ..
.. nesaemia, metabolic acidosis, catecholamine infusion, volume over-
• In patients with haemodynamic instability due to new-onset AF .. load, increased sympathetic tone, and bacterial superinfection. In
and AFL, electrical cardioversion should be considered. This,
..
. these patients, calcium antagonists may be preferred to beta-
Acute treatment of new atrial fibrillation or atrial flutter episode
Stable haemodynamic Synchronized

N
status DC shock AND

Rhythm control
Y Check interaction with
antiviral drugs
Class I AAD
Fast ventricular rate
Sotalol
and acute pulmonary
Amiodaronea
involvement
AND
Y
ANTICOAGULATION
Rate control CHA2DS2-VASc ≥ 1
Reasses rhythm after Check interaction with
recovery from antiviral drugs
COVID-19 infection Amiodaronea
Beta-blocker Still symptoms or
(Digoxin) haemodynamic
Diltiazem/Verapamil consequences
AND
AND
Reevaluate rate vs
ANTICOAGULATION
rhythm control and
CHA2DS2-VASc ≥ 1
anticoagulation strategy
Target for K+ ≥ 4.5 mEq/L and supplement with i.v. magnesium, correct hypoxia and acidosis
Adjust inotropic medication ( dopamine, dobatumine and epinephrine)
Consider transthoracic echocardiography if haemodynamic unstability or therapeutic consequences
If new LV dysfunction, consider myocardial injury and escalation of immunosuppressive therapy
Figure 5 Atrial tachyarrhythmias. CHA2DS2-VASc, congestive heart failure, hypertension, age >_75 years, diabetes mellitus, stroke, vascular dis-
ease, age 65–74 years, sex category (female); COVID-19, coronavirus disease 2019; DC, direct current. aThe benefit of intravenous amiodarone
treatment should be balanced against the proarrhythmic risk in patients taking QT-prolonging antiviral therapy.
..
blockers for rate control to avoid further worsening of the pul- .. currently insufficient evidence to recommend a different anticoa-
monary status. .. gulation scheme for patients with or without AF. Therapeutic anti-
• In hospitalized patients with new-onset AFL, rate control may be .. coagulation should be considered in male and female patients with
..
more challenging than AF. If the patient remains symptomatic or .. CHA2DS2-VASc score >_1 and >_2, respectively, and is indicated in
there are haemodynamic consequences, electrical cardioversion .. male and female patients with CHA2DS2-VASc score >_2 and >_3,
..
may be considered. .. respectively.
• Anticoagulation for the prevention of AF-related stroke or system- .. • The need for an echocardiogram should be balanced against the
ic embolism should be guided by the CHA2DS2-VASc score. In .. need for close contact between HCP and patient, and contamin-
..
spite of the thrombophilic environment in COVID-19, there is .. ation of equipment. Only when considered mandatory for
.
..
immediate therapeutic management, it can be used to assess LV .. likely low. In these rare cases, malignant ventricular arrhythmia may
function and pericardial and myocardial involvement. .. occur in the setting of underlying myocardial infarction, pulmonary
Transthoracic echocardiogram/echocardiography (TTE) is in gen- ..
.. embolism, stress cardiomyopathy, or acute myocarditis. In contrast,
eral preferred to transoesophageal echocardiography (TOE) to .. in critically ill patients, malignant ventricular arrhythmias are a marker
avoid aerosol generation. If possible, TTE should be deferred until ..
after convalescence.
.. of disease severity and occur more frequently in the terminal phase
.. of the disease, similar to the high incidence of ventricular arrhythmias
• Similarly, TOE should be obviated by early start of anticoagulation ..
.. in other aetiology ARDS and critical illnesses.182 In patients with a his-
in new-onset AF and in patients with a low CHA2DS2-VASc score .. tory of CVD and ventricular arrhythmias, exacerbation of the known
to allow safe electrical cardioversion, also >_48 h. ..
• Drug–drug interactions including antiviral, antiarrhythmic, and anti- .. VT/VF may occur due to COVID-19 as the trigger. Although reports
..

coagulation drugs should be considered before administration (see .. are not yet available for COVID-19, a correlation between influenza
Section Treatment of SARS-CoV-2 infection). .. epidemic and increased appropriate ICD therapies has been
• After recovery from the COVID-19, the therapeutic choices of .. shown.183
..
rate and rhythm control should be re-assessed, and long-term .. Special considerations for the treatment of ventricular arrhythmias
anticoagulation should be continued based on the CHA2DS2- .. during the COVID-19 pandemic are depicted in Figure 6 and summar-
VASc score.
..
.. ized below:
..
.. • In unresponsive, unbreathing patients, the local Basic and Advanced
Ventricular arrhythmias. An initial single-centre retrospective study ..
from Wuhan analysed the occurrence and significance of malignant .. Life Support protocol should be followed. During basic life support,
.. ventilation is not performed, only cardiac compressions, to avoid
ventricular arrythmias in 187 hospitalized patients with COVID-19. .. the risk of ingestion of aerosols. For Advanced Life Support, only
Among the 187 patients, 28% of patients had elevated troponin T lev- ..
.. HCP with full PPE are eligible to perform intubation
els and 23% died. During hospitalization, malignant ventricular .. • In patients with VF, asynchronous defibrillation, and in patients
arrhythmias (defined as sustained VT or VF) occurred in 5.9% of ..
.. with haemodynamically unstable VT, synchronized electrical cardi-
patients. VT/VF occurred more frequently in patients with elevated .. oversion should be performed;
troponin levels (17.3% vs. 1.5%, P < 0.001).178 In two more recent .. • In patients with sustained monomorphic VT:
..
larger studies, the reported incidence of sustained ventricular .. • Electrical cardioversion should be considered, especially if the
arrhythmias in hospitalized patients was lower at 1.9% and 3.4%, re-
.. patient is already ventilated.
.. • Intravenous procainamide (if available and with follow-up of
spectively.160,161 An anecdotal case series described critically ill ..
patients with ARDS in the setting of severe COVID-19 dying of re-
.. QT interval changes) or lidocaine could be considered in
.. patients taking QT prolonging combination antiviral drugs and if
fractory ventricular arrhythmias despite normal baseline cardiac func- ..
tion.179 In a recent study of 140 hospitalized patients reaching final
.. the haemodynamic status permits.
.. • Intravenous amiodarone should be considered in patients with
disposition of discharge or death in New York, acute malignant car- .. known structural heart disease and impaired LV function. Its ac-
diac arrhythmia defined as VT/VF or AV block with hemodynamic in-
..
.. tion is slow for conversion of VT. Its combination with antiviral
stability or cardiac arrest occurred in 9% of the study population; 5% .. drugs should be checked (see Section Treatment of severe
..
had malignant VT/VF; and 3.5% AV block. Patients who died had .. acute respiratory syndrome coronavirus 2 infection).
higher troponin levels and, more frequently, acute malignant arrhyth- .. • In critically ill patients with COVID-19 and recurrent sustained
.. VT and recurrent VF (‘VT storm’), i.v. amiodarone is the antiar-
mia with a difference driven by ventricular tachyarrhythmias (17% as ..
compared to 4% of patients who were discharged, P = 0.01). Fatal .. rhythmic medication of choice, though, its combination with
.. antiviral drugs should be checked (see Section Treatment of
ventricular tachyarrhythmias invariably occurred in the presence of ..
severe metabolic imbalance and hypoxia. Only 12% of all deaths .. SARS-CoV-2 infection).
..
were classified as CV death, and most (67%) of these deaths occurred .. • Intravenous lidocaine may be considered as a safer but less effect-
in the setting of ST-elevation myocardial infarction.180 In a similar .. ive alternative to amiodarone, especially if underlying myocardial
.. ischaemia is suspected:
study, also from New York, the last documented rhythm and circum- ..
stances of death were analysed in 133 patients who died during the .. • Addition of sympathetic blockade (e.g. esmolol) should be
.. considered.
index hospitalizations with COVID-19. Suspected or confirmed ar- .. • Intubation, sedation and ventilation may be considered to abort
rhythmic death occurred in only 8.3% of the study population and ..
.. VT storm.
was associated with younger age, ventricular ectopy, mechanical ven- .. • Temporary PM implantation for overdrive termination may be
tilation, vasopressor use, longer QTc and LBBB on admission.181 It ..
.. considered, balancing the possible therapeutic benefit against
should be noted that in all the above-mentioned studies, .. the invasiveness of the lead placement with risk for personnel.
between 11% and 100% of the patients received hydroxychloroquine
..
.. In the absence of a functional cardiac catheterization laboratory,
and in up to 100% of the patients in combination with azithromy- .. floatation-guided temporary wire insertion may be considered
cin.160,179–181
.. in case of emergency.
..
In summary, recent studies suggest that sudden cardiac death .. • In patients with severe acute respiratory insufficiency, correction
(SCD) due to primary ventricular arrhythmia is infrequent in hospital-
..
.. of underlying reversible triggers should be considered, such as
ized patients with COVID-19. The incidence of primary malignant .. hypoxia, hypovolaemia, electrolyte abnormalities as hypokalaemia
ventricular arrhythmias in asymptomatic or mildly symptomatic non-
..
.. and hypomagnesaemia, metabolic acidosis, catecholamine infusions,
hospitalized patients with COVID-19 is currently unknown but is .. volume overload, increased sympathetic tone, tamponade,
Acute treatment of new episodes of ventricular tachyarrhythmias (VT/VF)
Y Stable haemodynamic status N

Polymorphic Polymorphic
Monomorphic Monomorphic Polymorphic
VT/VF VT/TdPVT
VT VT/VF VT/VF
QTc not prolonged QTc prolonged
i.v. magnesium
i.v. beta-blocker
QTc prolonging Isoprenaline Synchronized
(Elmolol) Stop QT prolonging
Defibrillation
antiviral therapy DC shock
i.v. lidocaine antiviral medication
Recurrent TdP/
N Y Recurrent VT/VF Advance life support protocol
brachycardia
Synchronized
Temporary
a DC shock if pts
i.v. amiodarone i.v. amiodaronea transveneous
mechanically
pacing
ventilated
Recurrent or continuing VT
Target for K+ ≥ 4.5 mEq/L and supplement with i.v. magnesium, correct
i.v. beta-blocker (Elmolol) hypoxia and acidosis
i.v. lidocaine or procainamide Adjust inotropic medication ( dopamine, dobatumine and epinephrine)
If QTc ≥ 460 ms consider stopping all QT-prolonging medications
Recurrent or continuing VT Consider transthoracic echocardiography if haemodynamic unstability or
therapeutic consequences
If new LV dysfunction, consider myocardial injury and escalation of
Synchronized immunosuppressive therapy
i.v. amiodaronea
DC shock Rule out myocardial ischaemia
In therapy refractory VT/VT and respiratory insufficiency, consider ECMO
Figure 6 Ventricular tachyarrhythmias. DC, direct current; i.v., intravenous; QT, QT interval; QTc, corrected QT interval; TdP, torsade de pointes;
VF, ventricular fibrillation; VT, ventricular tachycardia. aThe benefit of i.v. amiodarone treatment should be balanced against the proarrhythmic risk in
patients taking QT-prolonging antiviral therapy.
.. • Normalizing potassium level (target >_4.5 mEq/L);

pneumothorax, ischaemia, bacterial superinfection, and proar- ..
rhythmic drugs. .. • Intravenous magnesium supplementation;
• Special attention should be paid to the prevention of TdP VT in .. • Increasing heart rate by withdrawing bradycardic agents and, if
..
the setting of COVID-19. .. needed, by i.v. isoproterenol or temporary pacing (balancing
• TdP is a polymorphic VT associated with QT prolongation and .. benefit against the invasiveness of the lead placement with risk
.. for personnel). Isoproterenol is contraindicated in the setting of
may be triggered by QT prolonging antiviral drugs, especially in ..
combination with AADs (mainly sotalol), electrolyte disturbances .. congenital long QT syndrome (LQTS); and
(in particular Kþ and Mg2þ), renal dysfunction, and/or bradycardia, .. • In therapy refractory cases, i.v. lidocaine184 or oral mexiletine185
..
especially in females and in patients with LV hypertrophy or dimin- .. may be considered, based on limited clinical data.
ished LV function. .. • New-onset malignant ventricular arrhythmias may be a marker of
• Therapy of TdP VT consists of: .. acute myocardial injury and should trigger diagnostic cardiac evalu-
..
• TdP withdrawal of all QT prolonging drugs; . ation. Polymorphic VT without QT prolongation is not TdP but
..
usually signals ischaemia or acute myocardial injury. Inflammation .. Bradyarrhythmias
and cardiac biomarkers should be followed. Echocardiography .. In a recent US study of 107 hospitalized patients, first degree AV
should be considered in all patients with new malignant ventricular
..
.. block was reported in 18.7% of the patients and 0.9% developed
arrhythmia, to assess ventricular function and myocardial involve- .. transient Mobitz II AV block. PR interval (regardless of medication
ment. In case myocarditis is suspected, MRI could be considered ..
.. use or troponin elevation), QRS duration, and QTc interval signifi-
(see Guidance Part 1), as the diagnosis may warrant more aggres- .. cantly prolonged in all patients during admission.197 In a study of 135
sive immunosuppressive and antiviral treatment. ..
• After recovery from COVID-19, the need for secondary prophy- .. hospitalized patients in Wuhan, 8.1% were reported to have sinus
.. bradycardia on the ECG, 3.7% first-degree AV block, 0.7% type I se-
lactic ICD, catheter ablation, or wearable defibrillator (in case of ..
suspected transient cardiomyopathy due to myocarditis) needs to .. cond-degree AV block, and 1.5% third-degree AV bock.198 In an-
..

be evaluated. .. other study from Wuhan of 319 hospitalized patients, 6% were
.. reported to have sinus bradycardia on the ECG, 3.4% first-degree
Channelopathies. COVID-19 may occur in patients with known con-
.. AV block, and 0.6% second-degree AV block.199 In a large US study
..
genital LQTS, Brugada syndrome (BrS), catecholaminergic poly- .. of 1053 hospitalized patients followed on telemetry, second-degree
morphic ventricular tachycardia (CPVT) and short QT syndrome,
.. or higher AV block was reported in 0.4% of the patients.160 In an-
..
with a risk of pro-arrhythmia. The specific interactions of these chan- .. other recent study of 140 hospitalized patients reaching final dispos-
nelopathies and COVID-19 has recently been reviewed.186
.. ition of discharge or death in New York, acute malignant AV block
..
In the initial phase of the pandemic, a combination of antiviral drugs .. defined as AV block with hemodynamic instability or cardiac arrest
including (hydroxy-) chloroquine and azithromycin was used exten-
.. occurred in 3.5% (five patients) of the study population.180 In two of
..
sively, with documented prolongation of the QTc and occurrence of .. the five patients, the AV block was associated with AMI, two other
..
related TdP.187,188 Recent randomized drug trials have demonstrated .. patients were critically ill and one patient had non-ST-segment eleva-
that (hydroxy-)chloroquine is not beneficial, so its use is largely aban- .. tion MI and newly depressed LV systolic function.180 Anecdotal
..
doned.189 Similarly, azithromycin has been shown not to confer .. reports have described additional cases of in the majority transient
benefit as compared to usual care.190 However, when used in isola- .. type II second degree or third-degree AV block in most cases associ-
..
tion as an antimicrobial among patients with COVID-19 azithromycin .. ated with troponin rise and myocarditis.200–203 In one of these cases,
may present a risk of QT prolongation.191 Azithromycin in isolation .. MRI was performed and revealed oedema of the interventricular
..
may still be used and is under ongoing evaluation, though it may still .. septum indicative of myocarditis.204 Interestingly, this patient was
present a risk of further QT prolongation.191 .. asymptomatic with COVID-19, had no troponin rise and, as the AV
..
A special consideration in congenital LQTS with COVID-19 is the .. block did not resolve, he underwent permanent PM implantation.
observation that in COVID-19 patients the QTc is consistently pro- .. Another anecdotal report described two patients with severe
..
longed.192 A combination of factors, including hypoxia, electrolyte .. COVID-19 and moderate new-onset sinus node dysfunction not
disorders, high interleukin (IL)-1, and IL-6 levels, is probably respon- .. resolving during 2 weeks of follow-up but not requiring PM implant-
..
sible.192 LQTS patients may, therefore, be at increased risk for ven- .. ation at last follow-up.205
tricular arrhythmias. The QTc should be monitored as closely as is
.. In summary, exacerbation of known conduction system or sinus
..
safe and practicable. All unnecessary QT prolonging drugs should be .. node disease or severe new-onset AV conduction or sinus node dys-
stopped, and if QTc is >500 ms or if QTc increases by >_60 ms from
.. function may occur in approximately up to 3% of patients with
..
baseline, then the safety of QT prolonging antiviral drugs, if still used, .. COVID-19. Mild-to-moderate AV conduction or sinus node dysfunc-
should be reviewed and serum potassium levels should be kept at
.. tion may occur in up to 10–20% of patients with COVID-19 and may
..
>4.5 mEq/L (Section Treatment of SARS-CoV-2 infection). .. be transient. In critically ill patients in the ICU, transient bradycardia
In BrS with COVID-19, the main concern is fever-triggered malig-
.. and asystole may occur due to patient turning for prone respiration,
..
nant ventricular arrhythmia. As shown in recently published case .. intubation, or trachea suction and is probably due to transient in-
.. crease in vagal tone.162 Severe new-onset bradyarrhythmia may be a
reports, COVID-19-induced fever may uncover the type 1 Brugada ..
pattern193 and lead to symptomatic BrS in previously unsuspected .. marker of acute myocardial injury due to ischaemia, hypoxia or myo-
..
cases.194,195 It has also been reported to cause electrical storm in a .. carditis and, if unexplained by the respiratory status, it should trigger
known BrS patient with an ICD implant.196 Therefore, in all COVID- .. diagnostic cardiac evaluation. Long-term outcomes of new-onset bra-
..
19 patients with BrS, fever should be aggressively treated with para- .. dyarrhythmia are unknown.
cetamol. ECG monitoring should be considered if antipyretic therapy .. Special considerations for permanent PM implantation in
..
is ineffective, and the temperature remains >38.5 C in higher-risk .. patients with COVID-19 include the poor prognosis of patients
BrS patients (Figure 7). .. requiring mechanical ventilation, increased risk of bacterial super-
..
In patients with CPVT and COVID-19, beta-blockers and flecainide .. infection and device infection in the critically ill patients, risk of
should be continued with monitoring of drug interactions with anti- .. nosocomial infection during device implantation in COVID-19
..
viral drugs (see Section Treatment of SARS-CoV-2 infection) and in .. negative patients, the possibly transient character of the bradyar-
critically ill patients, catecholamine infusions should be administered .. rhythmia in myocarditis, and transient bradyarrhythmic side effects
..
with great caution, as they require continuous monitoring. .. of antiviral therapy.
..
.
Patients with Brudaga syndrome Brugada syndrome

Confirmed/suspected COVID-19 and fever type 1 pattern

Immediate self-treatment with paracetamol/acetaminophen
Y ICD present
Low-risk group High-risk group

Drug-induced type 1 BrS Sodium channel mutation carrier
No cardiac syncope at any time < 26-years old
N > 70-years old
No spontaneous type 1 at any time
Spontaneous and/or known fever
induced type-1 ECG pattern
Cardiac syncope (NOT a simple faint)
N Fever ≥ 38.5 °C after treatment
Contact hospital, admission advised

N
Record ECG for type 1 BrS patterna
Monitor for arrhythmia
Follow public health protocol
+/- Self-isolation at home
Attend hospital only if other emergencies
require treatment e.g. syncope, shocks, Fever settles and/or type I BrS ECG
Y
breathlessness absent or resolves
Figure 7 Channelopathies. BrS, Brugada syndrome; COVID-19, coronavirus disease 2019; CPVT, catecholaminergic polymorphic ventricular
tachycardia; ECG, electrocardiogram; ICD, implantable cardiac defibrillator. aIdeally ECG recordings with V1 and V2 in the fourth, third, and second
intercostal spaces.
• Some treatments used for COVID-19 might increase the likeli- .. medications should be alerted to symptoms of dizziness, presyn-
..
hood for conduction disturbances (see Section Treatment of .. cope or syncope, and be instructed to contact medical care if
SARS-CoV-2 infection). Some of these effects might become ap- .. these occur.
.. •
parent only after several weeks. .. To avoid bradycardia as the result of drug–drug interactions, mon-
• Recovered COVID-19 patients with mild-to-moderate conduction .. itoring drug levels and dose adjustment may be required (see
disturbances or bradyarrhythmic side effects from antiviral
.. Section Treatment of SARS-CoV-2 infection).
..
.
• In case of persistent severe symptomatic bradycardia due to AV severely ill COVID-19 patients may be switched to
block or recurrent sinus node dysfunction with pauses: parenteral anticoagulation, which has no clinically relevant
• All medication causing bradycardia should be stopped. drug–drug interactions with COVID-19 therapies (with the
• Isoprenaline and atropine should be administered. exception of azithromycin, which should not be co-
• Temporary PM implantation should be considered. administered with UFH).
• New-onset severe symptomatic AV conduction or sinus node • Acute renal deterioriation or failure precludes continuation
dysfunction not explained by respiratory status should trigger of (the same dose of) NOACs and should therefore be
closely surveilled.
diagnostic cardiac evaluation. Ischaemia and hypoxaemia should
be excluded. Echocardiography should be considered to assess
ventricular function and myocardial involvement. In case myo-

carditis is suspected, MRI could be considered (see Guidance ..
Part 1) as the diagnosis may warrant more aggressive immuno- .. Medical treatment of COVID-19
suppressive and antiviral treatment. .. Despite the lack of definitive evidence on their efficacy, several drugs
• After recovery from the COVID-19, the need for permanent
..
.. with antiviral, anti-inflammatory or immunomodulatory properties
PM implantation should be reassessed. .. have been used ‘off-label’ to treat SARS-CoV-2 infection. Large
..
.. randomized trials have now identified several therapies, which in
.. combination can approximately halve mortality for patients hospital-
..
.. ized with COVID-19.
..
Treatment of SARS-CoV-2 ..
.. Anti-viral therapies
infection .. Several agents have been tested as repurposed antiviral agents.
..
.. Chloroquine, and its analogue hydroxychloroquine, has been
.. widely used as an antimalarial drug and in the treatment of rheumato-
..
Key points .. logical diseases like systemic lupus erythematosus and rheumatoid
..
• The evidence regarding the efficacy and risk of different .. arthritis. Following the observations of in vitro suppression of SARS-
.. CoV-2 growth,207–209 and in preliminary studies with reduced SARS-
treatment strategies in patients with COVID-19 is extensive ..
and continuously evolving; the current and regularly .. CoV-2 positivity in nasopharyngeal secretions,207 these drugs were
updated version of the World Health Organization (WHO)
.. initially used to treat COVID-19. However, randomized trials have
..
‘living guidelines’ is online available.206 .. not confirmed that hydroxycholoroquine is beneficial for the treat-
• Recent randomized clinical trials suggest that, with the .. ment of patients hospitalized with COVID-19.189,210–214 Hence,
exception of glucocorticoids (especially dexamethasone) in ..
.. chloroquine and hydroxychloroquine have no indication anymore in
hospitalized patients with severe and critical COVID-19, .. the treatment of COVID-19, although trials are ongoing of their role
the majority of the initially used antiviral, anti-inflammatory, ..
or immunomodulatory experimental drugs have no or .. in prophylaxis.215
limited effect on the natural history of COVID-19.
.. The protease inhibitor lopinavir–ritonavir was shown to be effect-
..
• In all patients undergoing antiviral treatment, it is of major .. ive against SARS coronavirus and MERS coronavirus in vitro and in ani-
importance to correct modifiable predisposing factors to .. mal models,216–218 but these findings have not been confirmed in
QTc prolongation: electrolyte imbalances, concomitant ..
.. randomized controlled trials of hospitalized patients with severe
drugs, and bradycardia. .. COVID-19.214,219,220
• Baseline ECG may not be needed in all before starting ..
treatment, especially if recent prior ECGs are available and .. In vitro and animal studies suggest that remdesivir (GS-5734) is ef-
there are no clinical signs suggesting CVD (e.g. unexplained
.. fective against zoonotic and epidemic SARS coronavirus and MERS
..
syncope). .. coronavirus.221–224 In vitro studies suggest that remdesivir compared
• Resource allocation will need to be adjusted locally .. to lopinavir–ritonavir.224 Preliminary studies suggested that remdesi-
depending on availability and demand. According to the
..
.. vir shortened the recovery time in hospitalized patients with
context, it is worth exploring alternative ECG monitoring .. COVID-19.225 However, larger randomized trials have reported lit-
methods (e.g. single lead and telemonitoring, smartphone- ..
enabled mobile ECG, handheld devices). .. tle or no effect on key outcomes such as or mortality, initiation of
• .. ventilation, and duration of hospital stay among hospitalized
In COVID-19 patients with an indication for oral ..
anticoagulant therapy, renal and liver function and drug– .. patients.214
drug interactions between oral anticoagulant and COVID- ..
19 therapies should be considered to minimize the risk of ..
.. Antibody-based therapies
bleeding or thromboembolic complications. ..
• In NOAC-eligible patients (i.e. those without mechanical .. Convalescent plasma obtained from people who have recovered
prosthetic heart valves, moderate to severe mitral stenosis .. from COVID-19 is also being used. Preliminary results from a large
or antiphospholipid syndrome), NOACs are preferred over
..
.. expanded-access program in the USA suggested that higher titres of
vitamin K antagonists (VKAs), owing to their better safety .. antibody had a larger impact on mortality as well as better outcomes
and fixed dosing without the need for laboratory ..
monitoring of anticoagulant effect, notwithstanding the .. when administered within the first 3 days after diagnosis.226
.. Importantly, this study did not have an untreated control group, so
importance of proper NOAC dosing and adherence to ..
treatment. .. findings should be considered with caution. The RECOVERY
• Whereas apixaban, rivaroxaban, or edoxaban can be given .. (Randomized Evaluation of COVID-19 Therapy) trial assessed high-
as oral solutions or crushed tablets (via enteral tubes),
..
. titre convalescent plasma among 11 558 patients hospitalized with
COVID-19 and found no benefit on major clinical outcomes.227 It ... Antithrombotic therapies
..
remains possible that convalescent plasma may have a role in earlier .. Antiplatelet agents had been proposed as a potential therapy, in part
disease, but this hypothesis needs to be tested. .. because of the high rate of venous and arterial thrombosis observed
..
More recently, synthetic monoclonal antibodies directed against .. in severe COVID-19. Among 14 892 patients in the RECOVERY trial,
the SARS-CoV-2 spike protein have been assessed in randomized .. aspirin did not improve clinical outcomes.
..
trials. In the USA, Emergency Use Authorization has been given for .. Trials of heparin-based anticoagulation have shown different
the use of bamlanivimab with etesevimab, REGEN-COV, and .. results by severity of disease. Among critically ill patients, no benefit
..
sotrovimab in non-hospitalized patients with mild-to-moderate .. of therapeutic anticoagulation compared to usual care was seen in
COVID-19, based on their ability to reduce viral load more quickly .. three trials. By contrast, these trials have separately reported that
..

and prevent need for hospitalization.228–230 Although small studies .. among non-critically ill hospitalized patients therapeutic anticoagula-
of these agents among hospitalized patients were terminated early .. tion increased organ support-free days.
..
for futility,231,232 REGEN-COV was assessed among 9785 partici- .. In summary, the current version (as of 31 March 2021) of the
pants hospitalized with COVID-19 in the RECOVERY trial.233 .. WHO living guidelines recommends not to use ivermectin in patients
..
Among seronegative participants (i.e. those without a detectable .. with COVID-19 except in the context of a clinical trial; strongly rec-
humoral response to SARS-CoV-2), allocation to REGEN-COV ... ommends against the use of hydroxychloroquine and lopinavir/ri-
reduced mortality at 28 days by 20% (24% vs. 30%: rate ratio 0.80,
.. tonavir in patients with COVID-19 of any severity; conditionally
..
95% CI 0.70–0.91). .. recommends against the use of remdesivir in hospitalized patients
.. and systemic corticosteroids in patients with non-severe COVID-19;
..
.. and strongly recommends for systemic corticosteroids use in patients
.. with severe and critical COVID-19.206
Immunomodulatory therapies ..
In the RECOVERY trial, dexamethasone reduced mortality in hos- ..
..
pitalized COVID-19 patients receiving oxygen, with the largest ef- ..
fect among patients receiving mechanical ventilation.54 This benefit .. Arrhythmologic consideration of COVID-19 therapies
.. One major concern with drugs used in COVID-19 is the very rare
was confirmed in a meta-analysis by the WHO REACT working ..
group of seven randomized clinical trials of critically ill patients .. risk of QTc prolongation and TdP/sudden death or the potential oc-
.. currence of conduction disturbances. A recent meta-analysis on
with COVID-19. The administration of systemic corticosteroids ..
(dexamethasone, hydrocortisone, or methylpredinisolone), com- .. arrhythmogenic cardiotoxicity of the quinolines and structurally
.. related antimalarial drugs suggested that this risk is minimal (no
pared with usual care or placebo, was associated with lower ..
28-day all-cause mortality.56 Benefits were also observed on pro- .. events of SCD or documented VF of TdP in 35 448 individuals, 1207
..
gression to invasive mechanical ventilation and need for renal re- .. of whom were taking chloroquine).222 During COVID-19, the
placement therapy. .. QT-related risk may be amplified by concomitant use of other
..
In vitro, azithromycin has shown to be active against the SARS- .. QTc-prolonging drugs and/or electrolyte imbalances (hypokalaemia,
CoV-2 virus.234 However, the COALITION I and II and
.. hypomagnesaemia, and/or hypocalcaemia). Furthermore, important
..
RECOVERY randomized trials did not show any benefit of adding .. drug–drug interactions have been described [mainly because these
azithromycin therapy in either mild-to-moderate or severe
.. potent CYP3A4 inhibitors interfere with (hydroxy)chloroquine me-
..
COVID-19.211,235 .. tabolism] that should be taken into consideration. In some combina-
In COVID-19 patients, IL-6 level is associated with viral load, dis-
.. tions, dose adjustments or changes may be needed (Table 4).
..
ease severity, and prognosis.236 Tocilizumab, an IL-6 receptor mono- .. For a detailed overview of all known direct or indirect (through
clonal antibody, has been proposed to treat severe COVID-19. The
.. drug–drug interactions) pro-arrhythmic effects of experimental
..
largest trial to date is RECOVERY, which demonstrated that among .. pharmacological therapies in COVID-19 patients, see Table 4.
..
patients with hypoxia and inflammation (CRP >_75 mg/L), tocilizumab ..
reduced the risk of death by 15% (rate ratio 0.85, 95% CI 0.76– ..
.. Corrected QT interval evaluation to prevent drug-
0.94).237 A WHO-led meta-analysis of all trials of IL-6 antagonists ..
confirms this benefit.238 .. induced arrhythmia
.. QTc prolongation by some drugs can theoretically lead to poly-
Colchicine has been proposed as an oral anti-inflammatory medi- ..
cation for the treatment of COVID-19 and several small studies, .. morphic VT (TdP). This is, however, a very rare complication, and its
.. risk has to be balanced against the anticipated benefit of therapy for
including the GRECCO-19 trial in 105 hospitalized patients,239 ..
yielded promising findings. In the COLCORONA randomized .. the COVID-19 patient. Figure 8 provides a practical flow chart for the
.. management of patients to prevent TdP, guidance on the timing and
placebo-controlled trial in community-treated patients including ..
those with suspected but with diagnostic test not confirmed COVID- .. repetition of ECG recordings, and QTc measurements that would
.. alter therapy. Other guidance flowcharts have been published.186,291
19, the effect of colchicine on COVID-19-related clinical events was ..
not statistically significant, although an analysis just among patients .. Briefly, the following steps are required to reduce the risk of drug-
.. induced TdP:
with PCR-confirmed COVID-19 did suggest that there may be a re- ..
duction in the composite of death or hospital admission in such ..
.. (1) Identify risk factors associated with QTc prolongation:
patients.240 However, a much larger randomized trial among patients .. • Non-modifiable risk factors: congenital LQTS, QT prolonga-
with more severe illness who had been hospitalized with COVID-19
.. tion on known QT prolonging drugs, female sex, age >65
..
found no benefit of colchicine.241 . years, structural heart disease (ACS, uncompensated HF,
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26
Table 4 Pro-arrhythmic considerations of novel experimental pharmacological therapies in COVID-19
Heart rate AV conduction QRS interval QTc interval TdP risk AAD drugs Comments
interactions242
..............................................................................................................................................................................................................................................................................................................
Chloroquine Mild # Mild " Mild " Moderate–severe " Very low risk of TdP (2 VT Severea • Very low risk of cardi-
DPR = 14.8 ms243 DQRS = 9.9 ms243 DQTc = 33–35 ms243–249 cases with high dosage and Amiodarone, flecainide, otoxicity during chron-
QTc > 500 ms or DQTc > 1 case report of TdP in mexiletine ic therapy is
60 ms in 15–23% of COVID patients)188,250,251 Moderateb reported252,253
patients244,246–248 Disopyramide, digoxin, • In a study in SLE, it was
dofetilide, propafenone, negatively associated
quinidine with AVB (P = 0.01) as
Mildc was its longer use
Metoprolol, nebivolol, (6.1 ± 6.9 vs.
propranolol, timolol, 1.0 ± 2.5 years,
verapamil P = 0.018)247
• Proarrhythmia occurs
mostly with overdos-
age or in chronic ther-
apy (> years)254
• Proemetic effect is
EHAB697 Copyedited by: Manuscript Category: Special Article Cadmus Art: OP-EHEA21070
common
• Risk of retinopathy,
myo/neuropathy dur-
ing chronic therapy is
reported
Hydroxychloroquine Mild # No changes in Mild " Moderate " Very low risk of TdP See chloroquine • Very low risk of cardi-
DHR = COVID patients256 DQRS = 0–3.7 ms251,259 DQTc= 5.5–16 ms (3 cases of TdP in COVID otoxicity during chron-
-5 ms254–258 QTc > 500 ms or DQTc > patients)187,189,210,211,261,265 ic therapy is
60 ms in 1–19% of reported250,253
patients187,244,251,256,259–264 • Proarrhythmia occurs
When associated with mostly with overdos-
azithromycine age or in chronic ther-
Moderate–severe " apy (> years)250
DQTc = 11–35 ms • Less cardiotoxicity
QTc > 500 ms or DQTc > reported than with
60 ms in 1–36% of chloroquine250
187,244,251,256,259–264 •
patients In a study of pregnant
women with Ro/La
antibodies, AVB was
more frequent in those
C. Baigent et al.
Continued

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Table 4 Continued
interactions242
..............................................................................................................................................................................................................................................................................................................
not using
hydroxychloroquine211
• Risk factors for severe
QTC prolonging in
COVID patients are
the use of loop diu-
retics, history of myo-
cardial infarction,
CKD, and heart failure,
prolonged QTc at
baseline187,189,210,
211,251,254,256,259–265
Azithromycin Mild #266 Mild "266 Mild "266 Moderate–severe " Low risk of TdP Severea In a study during treat-
DQTc = 0.5–25 ms Cumulative incidence SCD = Amiodarone, dofetilide, ment days 1–5,
QTc >500 ms or DQTc 64.6/1 million267 dysopiramide, flecainide, patients receiving

>60 ms in 19% of ROR for TdP = 4.76 com- propafenone, sotalol azithromycin had sig-
patients187,189,210,211,235, pared to other medication Moderateb nificantly increased
ESC guidance for the diagnosis and management of CVD during COVID-19: Part 2
244,251,256,259–266
(2.81–7.98)268 Beta-blockers, digoxin risk of serious arrhyth-
RR for SCD or VT = 3.40 mia (hazard ratio =
compared to no macrolide 1.77; 95% CI, 1.20–
use267,269,270 2.62) compared with
patients receiving
amoxicillin271,272
273 a
Lopinavir/ritonavir Moderate # Moderate " Mild " Moderate–severe " Low risk of TdP (1 case of Severe 5 cases of bradycardia
DPR = 33.5 ms243 DQRS = 7 ms274 (1 case DQTc = 14–20 ms TdP reported in COVID Amiodarone, disopyra- and one bundle
of bundle branch block QTc >500 ms in 21% of patients)219,273,275 mide, dofetilide, drone- branch block
reported in COVID patients273,275 darone, flecainide regressed upon drug
patients)273 Moderateb discontinuation273
2þ
All beta-blockers, Ca
blockers, digoxin, lido-
caine mexiletine, propa-
fenone, quinidine
Continued
27

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Table 4 Continued
interactions242
..............................................................................................................................................................................................................................................................................................................
Tocilizumab No ECG changes No ECG changes No ECG changes No ECG changes Clinical data showed Mildc
described276 described276 described276 described276 safety277–279 Amiodarone, quinidine
Fingolimod Moderate– Mild–moderate " Unknown Mild " Unknown Moderateb Reported risk of rare,
severe # Amiodarone, beta-block- transient and benign
DHR = -23 ers, Ca2þ blockers, fle- bradycardia and AV
bpm280 cainide, ivabradine, conduction
propafenone abnormalities:281
• In a study of 3591
patients, 31 patients
(0.8%) developed
bradycardia (<45
b.p.m.), 62 patients
(1.6%) had second-de-
gree Mobitz Type I,
and/or 2:1 AV
blocks282
patients, new-onset
first-degree AVB was
experienced by 132
(2.4%) in-home and 74
(0.5%) in-clinic
patients, and
Wenckebach (Mobitz
Type I) second-degree
AVB by four (0.07%)
and nine (0.1%)
patients, with no cases
of third-degree
AVB.283
patients with MS, fin-
golimod lead to an in-
crease of vagal
activation, which per-
sisted even after
Continued
C. Baigent et al.

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Table 4 Continued
interactions242
..............................................................................................................................................................................................................................................................................................................
14 months of
treatment.280
Remdesivir No ECG changes described284 Clinical data showed Unknown

safety285,286
Corticosteroids No ECG changes described287,288 Clinical data showed NR • May cause electrolyte
safety286,287 disturbance
• High-dose intravenous
prednisolone might
cause acute sinus
bradycardia289,290 or,
in MS patients, sinus
tachycardia, bradycar-
dia, and rarely AF and
VT289
Interferon alfacon-1 Unknown Unknown Unknown Unknown Unknown Unknown Limited data: cases of
hypotension, arrhyth-
mia, and cardiomyop-
athy reported
ESC guidance for the diagnosis and management of CVD during COVID-19: Part 2
Ribavirin Unknown Unknown Unknown Unknown Unknown Unknown No cardiac side effect
AF, atrial fibrillation; AV, atrio-ventricular; AVB, AV block; AAD, antiarrhythmic drugs; CI, confidence interval; CKD, chronic kidney disease; COVID-19, coronavirus disease 2019; HR, heart rate; LAFB, left-anterior fascicle block; LQTS, long QT syn-
drome; MS, multiple sclerosis; NR, not reported; OR, odd Ratio; QTc, corrected QC interval; RBBB, right-bundle branch block; ROR, reporting odd ratio; RR, risk rate; SCD, sudden cardiac death; SLE, systemic lupus erythematosus; TdP, torsade de
pointes; VT, ventricular tachycardia.
a
These drugs should not be co-administered.
b
Potential interaction (need dose adjustments/close monitoring).
c
Weak intensity interaction (need dose adjustments/close monitoring unlikely to be required).
29

Prevention of torsades de pointes for COVID-19 patients under antiviral therapy
Patient with known
Congenital long QT syndrome

N Acquired LQTsa Y
Use of QT-prolonging medication
Structural heart disease
Bradycardia < 50 bpm
ECG or monitor strip

with lead I or II
QTc ≥ 500 ms Y
Start antiviral treatment Start antiviral treatment

for 1 day for 4 hours
ECG ECG
QTc ≥ 500 ms
QTc ≥ 500 ms or
Continuation
or N N QTc increase > 25%
therapyb
ventricular ectopy or
ventricular ectopy
Y Y
Consult
cardiology
Figure 8 QTc management. COVID-19, coronavirus disease 2019; ECG, electrocardiogram; LQTS, long QT syndrome; QTc, corrected QC inter-
val. aAs long as the patient is clinically stable (e.g. no pronounced vomiting, diarrhoea, signs/symptoms of heart failure or deterioration of respiratory,
or other organ function).
..
hypertrophic cardiomyopathy), renal impairment, and liver .. of developing TdP or sudden death. The risk-benefit ratio of treat-
impairment. .. ment in this group should be carefully assessed. In some patients
• Modifiable risk factors: hypocalcaemia, hypokalaemia, hypo- .. with a recent ECG showing normal QTc and no evidence of major
..
magnesaemia, concomitant use of QTc-prolonging medica- .. CV alterations due to COVID-19, one may consider not taking a
tions, and bradycardia. .. baseline ECG to avoid exposure to HCP and contamination of
..
.. equipment.
(2) Identify and correct modifiable risk factors in all patients. Serum po- .. (4) Perform ECG once on treatment. If the patient has a QTc >_500 ms
tassium should be kept in the higher range (>_ 4.5 mEq/L).292
.. or shows a DQTc >_60 ms, switching to a drug with lower risk of
..
(3) Perform a baseline ECG (12-lead or single strip, depending on re- .. QTc prolongation, reduction of the administered dose, or continu-
source availability). Patients with a baseline QTc >_500 ms are at risk .. ing treatment plan are the options to consider. Close surveillance of
..
QTc interval (preferably including telemetry for arrhythmia moni- .. therapies with VKAs, NOACs, LMWHs, and UFH. The table includes
toring) and electrolyte balance are mandatory. .. information that was derived from several drug interaction sites,
..
.. which have been referenced. Drug summary of product characteris-
Bradycardia prolongs QT and facilitates TdP. While some COVID- .. tics often do not contain information for older drugs and/or drugs
..
19 drugs have a weak bradycardic effect, the concomitant use of .. with a narrow spectrum of indications (like chloroquine).
beta-blockers, CCBs, ivabradine and digoxin should also be eval- .. Antimalarial drugs have a P-glycoprotein inhibiting effect, which may
..
uated. If digoxin is considered mandatory for the patient, plasma level .. affect NOAC plasma levels. COVID-19 patients on oral anticoagula-
monitoring should be considered (with ensuing dose reduction if .. tion may be switched over to parenteral anticoagulation with LMWH
..
needed). .. and UFH when admitted to an ICU with a severe clinical
..

.. presentation.
Technical aspects of QT measurements
.. We would like to reiterate here also that the conventional dose
.. reduction criteria for NOACs for AF patients on oral treatment for
For patients with wide QRS complex (>_120 ms) due to bundle ..
.. stroke prevention can be continued. For more details, including the
branch block or ventricular pacing, QTc adjustment is needed. ..
Formulae are available, but a simpler approach may be to use a QTc .. assessment of renal and liver function and other considerations in
.. patients taking an NOAC, please see the 2021 EHRA Practical Guide
cut-off of 550 ms instead of 500 ms. Others propose to calculate ..
adjusted QT interval by subtracting QRS width and adding 100 ms. .. on the use of NOACs in patients with AF.302 Of note, none of the
.. NOACs is recommended in patients with a creatinine clearance
A standard 12-lead ECG may not always be feasible to obtain, es- ..
pecially in times of sudden outbreak and scarce healthcare resources. .. (CrCl) <15 mL/min according to the EU label.
..
As an alternative, enhanced use of handheld ECG devices should be .. • Apixaban: the standard dose (2 x 5 mg) should be reduced to 2 x
encouraged to reduce traditional ECG recording to preserve resour- .. 2.5 mg if two out of three criteria are met [body weight <_60 kg,
..
ces and limit virus spread. In a recent study, the QTc in lead-I and .. age >_80 years, serum creatinine >_133 mmol/L (1.5 mg/dL)], or if
lead-II derived from a standard 12-lead ECG was compared with the .. the CrCl is 15–29 mL/min.
.. • Dabigatran: the standard doses 2 x 150 and 2 x 110 mg. No pre-
QTc measured from a rhythm strip from a handheld ECG device in ..
99 healthy volunteers and 20 hospitalized patients in sinus rhythm .. specified dose reduction criteria but, per the drug label, 2 x 110
.. mg should be used if age >80 years, concomitant verapamil,
treated with dofetilide or sotalol.293 QT on the handheld device had ..
an excellent agreement with standard 12-lead ECG both in the nor- .. increased risk of gastrointestinal bleeding.
.. • Edoxaban: the standard dose (1 x 60 mg) should be reduced to 1
mal range and in patients with QT prolongation.293 This handheld .. x 30 mg if weight <60 kg, CrCl <50 mL/min, concomitant therapy
ECG device (KardiaMobile 6L Alivecor) had a high specificity for
..
.. with a strong P-gp inhibitor.
detecting a QTc >450 ms and should thus be considered as an effect- .. • Rivaroxaban: the standard dose (1 x 20 mg) should be reduced to
ive outpatient tool for monitoring patients with prolonged QTc.
..
.. 1 x 15 mg if CrCl <50 mL/min.
Recently, KardiaMobile 6L received expedited approval from the ..
FDA for QT monitoring and can thus be used in COVID-19 patients
..
.. For patients with impaired swallowing, NOACs can be adminis-
treated with QT prolonging drugs. .. tered in the following ways:
..
.. • Administration in a crushed form (e.g. via a nasogastric tube) does
..
Considerations on the use of .. not alter the bioavailability of apixaban, edoxaban and rivaroxa-
anticoagulants in COVID-19 patients .. ban.303–305
..
Recent studies confirm that COVID-19 is associated with increased .. • Apixaban can be given as oral solution or via nasogastric or gastric
risk of venous, arterial, and microvascular thrombotic and thrombo-
.. tube on an empty stomach (food impairs bioavailability of the
..
embolic disease, including disseminated intravascular coagulation .. crushed tablets).306
.. • Rivaroxaban tablet can either be crushed and mixed in water or
(see Guidance Part 1 and Section Acute pulmonary embolism—pre- .. apple puree and taken orally, or suspended in water and given via
vention and diagnosis).294–297 In general, the risk of thrombotic com- ..
.. nasogastric tube (enteral tubes must not be distal to the stomach)
plications and bleeding should be assessed in all patients with .. followed by food.304
COVID-19, and current guidelines for the prevention and treatment .. • Dabigatran capsules must not be opened, as it would result in a
..
of thrombotic and thromboembolic diseases should be fol- .. 75% increase in the drug bioavailability.306
lowed.151,298 Specific in COVID-19, in two recent studies, the use of ..
..
reduced and therapeutic-dose anticoagulation has been associated ..
with improved outcomes and mortality in hospitalized patients.295,296 ..
.. Patient information
The indications and details of venous and pulmonary embolism ..
prophylaxis and treatment of thrombotic complications of COVID- .. While there remain unknown features of COVID-19,307 it is clear
..
19 are discussed in Section Acute pulmonary embolism—prevention .. that transparent patient-centred information is an essential compo-
and diagnosis and have been reviewed in several recent consensus .. nent to support patients to reduce risk of transmission, maintain a
..
documents.294,297 .. healthy lifestyle and manage their CVD (Figure 9). What is the full
Many patients with CV history have an indication for anticoagula-
.. spectrum of disease severity? What is the transmissibility? What is
..
tion and are already under anticoagulation therapy when affected by .. the role of asymptomatic/pre-symptomatic infected persons? How
COVID-19. Table 5 lists the possible interactions of COVID-19
.. long is the virus present? What are the risk factors for severe illness?
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Table 5 Interactions of anticoagulant drugs with experimental COVID-19 therapies
COVID-19 therapies NOACs Comments VKAs LMWH, UFH

anticoagulants
............................................................................... ................................................... .....................................................................
Dabigatran Apixaban Edoxaban Rivaroxaban Warfarin Aceno- Phenpro- Enoxaparn Fonda- Dalteparin Heparin
etexilate coumarol coumon parinux
................................................................................................................................................................................................................................................................................................
Chloroquine242,299,300 " " " " Any NOAC may be
Hydroxychloroquine242,299,300 " " " " used (with caution)
Azithromycine20,70,272 " " If CrCl <30 mL/min dabi- " "a
gatran should be
avoided.
If renal function is
impaired (CrCl
<50 mL/min), rivarox-
aban should be used
with caution.
Atazanavir242,300,301 "b "b "c "b Reduced-dose edoxaban " "
d d
" " "d (30 mg o.d.) may be
used with caution
Lopinavir/ritonavir242,299–301 $or# "e "b " Dabigatran may be used # # #"
Darunavir/cobicistat with caution (should be
avoided if CrCl
<30 mL/min)
Ribavirin242,299–301 Any NOAC may be used #
Remdesivir242,299,300 (with caution)
Favipiravir300
Bevacizumab300
Eculizumab300
Tocilizumab242,299,300 # # # # #
Fingolimod299,300
Interferon299,300
Pirfenidone299,300
Methylprednisolone299,300 # #
Nitazoxanide242,300 " " "
Light grey colour: no information found. Green colour: no clinically significant interaction is expected, or potential interaction is likely to be of weak intensity, not requiring additional action/monitoring or dose adjustment. Yellow colour:
potential interaction which may require additional monitoring (e.g. more frequent INR monitoring if on VKAs). Orange colour: potential interaction which may require a dose adjustment. Red colour: the drugs should not be co-adminis-
tered. ", potential increased exposure to the anticoagulant drug; #, potential decreased exposure to the anticoagulant drug; $, no significant effect on the exposure to the drug.
COVID-19, coronavirus disease 2019; CrCl, creatinine clearance; LMWH, low molecular weight heparin; NOACs, non-vitamin K antagonist oral anticoagulants; o.d., once daily; UFH, unfractionated heparin; VKAs, vitamin K antagonists.
a
Azithromycin increases the effect of heparin by decreasing its metabolism.300
b
There is an overall agreement that the use of NOACs is not recommended when atazanavir is given in combination with its enhancers, ritonavir or cobicistat.
c
The EMA product label for edoxaban advises the consideration of dose reduction from 60 mg once daily to 30 mg once daily with concomitant use of strong P-glycoprotein inhibitors.
d
No data on the safety/efficacy of use of NOACs when co-administered with atazanavir are known; if their use is deemed indicated, one should consider monitoring plasma level of the NOACs in this unknown condition, in line with the
recommendation that was made in the last EHRA Practical Guide.298
e
C. Baigent et al.
The US product label for apixaban proposes the use of apixaban at reduced dose (2.5 mg twice daily) if needed.

Drink plenty of water

or enjoy a cup of tea or
coffee in a quiet place
Spend time escaping Exercise - walk

with a recreational around the garden,

activity like reading or try an online class
Focus on your
Advice for patients Use virtual methods
breathing from the ESC of socializing
patient forum
Eat well, regularly Avoid excessive

and healthily negative messaging
Stay busy with chores,

such as gardening
and cleaning
Figure 9 Advice for patients from the European Society of Cardiology patient forum.
Knowledge is being accumulated very fast and our task is to deliver ..

key information for patients with CVD.
.. Table 6 Concomitant conditions that may be associ-
.. ated with a more severe course of SARS-CoV-2
.. infectiona
..
Key points ..
.. Chronic pulmonary disease
..
• Patient-centred information is of paramount importance .. History of heart failure
during the COVID-19 pandemic when the allocation of .. Waiting list for cardiac surgery
medical resources is a matter of debate.308
..
.. Immunodeficiency or prior organ transplantation
• Pre-existing CVD has a direct impact on the risk of SARS- .. Hypertension
CoV-2, severity of COVID-19 disease, and survival.112 ..

• The occurrence of SARS-CoV-2 may lead to CV .. Coronary artery disease
.. Cerebrovascular disease
complications as well as treatments used to cure the ..
COVID-19 disease. .. Diabetes
• Unambiguous information to the population and patients is .. Severe overweight (BMI >40 kg/m2)
..
key for better control of the disease and the rapid .. Arrhythmias
development of specific treatment strategies, including ..
vaccines. .. BMI, body mass index.
.. a
Many of these features are confounded by age.
..
..
..
Who is at risk for severe SARS-CoV-2? ..
.. continue or discontinue their treatment with ACEIs or ARBs (see
There are several clinical features associated with a worse short- ..
.. Section Hypertension).126,127
term outcome of SARS-CoV-2 manifestations (see Guidance Part 1). .. • There are some treatments that may need to be adjusted when
These include: age >65-year old with a least one comorbidity, or age ..
.. concomitant specific therapy for the COVID-19 disease is initiated.
>70-year old, with the risk being highest in age >80-year old; COPD, .. These treatments are initiated during hospital admission and po-
asthma, chronic HF, certain cardiac arrythmias, recent unstable cor- .. tential drug–drug interactions are summarized inTables 6 and 7.
..
onary artery disease or coronary revascularization (<3 months), BMI ..
>35 kg/m2 or BMI >30 kg/m2 plus one or more comorbidities, sickle ..
..
cell anaemia, transplant <6 months, hypertrophic cardiomyopathy ..
with obstruction, chronic kidney disease (eGFR <15 mL/min), and .. Interactions with others, healthy
..
dysregulated diabetes.309 The effect of social background and .. lifestyle, and medical advice during
ethnicity on survival remains controversial, but it appears that ..
.. COVID-19 pandemic
long-standing disparities in nutrition and obesity play a crucial role in .. The following information is important for individuals with CVD
the health inequities unfolding during the pandemic (see Guidance ..
.. (Figures 9 and 10):
Part 1).310–313 A cause-and-effect relationship between drug therapy ..
and survival should not be inferred given the lack of ongoing random-
.. • Interaction with others:
.. • Avoid people who are sick.
ized trials. Patients should be informed and take appropriate precau- ..
.. • Keep a two-metre distance from other individuals whenever
tions with emphasis on measures for social distancing when the .. possible.
potential risk is high and medical resources are scarce. .. • Wash hands thoroughly with soap and warm water for at least
..
.. 20 s.
.. • Cover the mouth or nose with a tissue or use the inside of the
My treatment during the COVID-19 ..
.. elbow when you cough or sneeze.
pandemic .. • Avoid touching the eyes, nose and mouth when you are with
..
• COVID-19 disease may trigger destabilization of chronic CVD. .. other people.
This may also be favoured by chronic oral treatment interruption,
.. • To remove the virus, clean surfaces like doorknobs or handles
.. often with a disinfectant.
and patients should be informed to seek medical guidance prior to ..
any treatment modifications. .. • Self-isolate in case of symptoms of fever, cough or a chest infec-
• Aspirin dosage given for the secondary prevention of athero-
.. tion and look for medical assistance.
.. • Limit/avoid situations with high risk of becoming infected.
thrombosis has no anti-inflammatory potential and should not be ..
interrupted in COVID-19 patients without any other relevant rea-
.. • Stay at home as much as possible.
.. • Maintain physical activity to avoid VTE and maintain well-being.
sons, such as ongoing bleeding complication or the need for an ..
unplanned invasive procedure. ..
• Many patients at potential risk for SARS-CoV-2 are treated with
..
.. In addition, individuals should be encouraged to follow the instruc-
inhibitors of the RAS, including ACEIs. ACE2 facilitates coronavirus .. tion of the Department of Health and local authorities in the resident
entry into cells, but it is not inhibited by ACEIs or Ang II type 1 re-
..
.. countries, as these may differ.
ceptor blockers or upregulated by these treatments. For these ..
reasons, patients should not discontinue their treatments without .. • Healthy lifestyle:
.. • Maintain a healthy lifestyle (e.g. eat healthy, quit smoking, re-
medical guidance.134,314 Two randomized controlled trials have ..
shown that there was no difference in major outcomes from .. strict alcohol intake, get adequate sleep and keep physically
COVID-19 whether or not the patients were randomized to
.. active).315
Table 7 Potential interactions of drugs to treat COVID-19a
Drugs used to treat COVID-19 Interactions Action

....................................................................................................................................................................................................................
Dexamethasone Warfarin Monitor INR
Methylprednisolone Warfarin Monitor INR
Antiretroviral drugs Antiarrhythmics Use QT prolonging or low-dose digoxin with caution
NOACs Avoid apixaban and rivaroxaban
Statins Start with low-dose rosuvastatin or atorvastatin

Warfarin Monitor INR
Colchicine Statins Consider reducing dose of statin therapy
CYP3A4 inhibitor Consider reducing dose of colchicine
Chloroquine or hydroxychloroquine Beta-blockers and QT prolonging drugs Monitor ECG
COVID-19, coronavirus disease 2019; ECG, electrocardiogram; INR, international normalized ratio; NOACs, non-vitamin K antagonist oral anticoagulants.
a
These medications will be administered during hospital admission.
Supplying physical
help with online and
digital resources
Ensuring
Ensuring access
reimbursement for
to medications
telehealth is secured
Build a connected home
Telehealth during COVID-19

for people with CVD
Appropriate and Preparing staff to
timely access to deliver effective
emergency care telehealth solutions
Supporting mental
Access to healthy food
health with online and
and other vital supplies
digital resources
Figure 10 Telehealth during COVID-19 for people with cardiovascular disease.

..
• Isolation and physical restrictions may lead to inactivity, .. (European Society of Cardiology) coordinated the development of
increased risk of VTE, and loss of functional autonomy, especial- .. the article.
..
ly among elderly with co-morbidities. ..
• Physical activity should be strongly encouraged, either in a .. Conflict of interest: C.B. reports grants or contracts as follow:
home setting or outdoor areas with social space, and will also .. Medical Research Council: Population Health Research Unit
..
improve well-being. .. (Director) 2019–24, Medical Research Council: PHRU capital award
• Attending cardiac rehabilitation (in person or virtual) should be .. 2019–20, Medical Research Council: Therapy Acceleration
encouraged for those with an indication.
..
.. Laboratory Award 2021; BHF: Project Grant no. PG/18/16/33570
• Maintaining a social network (virtually if required) should be .. Cholesterol Treatment Trialists’ (CTT) Collaboration: Meta-analyses
encouraged. ..
.. of individual participant adverse event data from randomized con-

• Stay mentally active. Undertake enjoyable activities, which re- ..
.. trolled trials of statin therapy (co-applicant) 2018–20; Boehringer-
quire concentration (e.g. read books, listen to music, paint) and
take breaks from watching news on COVID-19.
.. Ingelheim: EMPA-KIDNEY trial (study co-chair) 2018–22; NIHR HTA
.. 17/140/02: Cost-effectiveness of statin therapies evaluated using indi-
• Physical activity trackers significantly increase physical activity ..
and may be a useful adjunct to promote a healthy lifestyle .. vidual participant data from large randomized clinical trials (co-appli-
.. cant) 2018–22. C.B. reports unpaid roles as chair of the European
remotely.316 ..
.. Society of Cardiology Clinical Practice Guidelines Committee and as
• Medical advice: ..
.. vice-chair of the British Heart Foundation Clinical Studies
• Continue with prescribed medications for CVD.
• Seek medical help immediately if experiencing symptoms such
.. Committee. S.W. reports research and educational grants via his in-
.. stitution from Abbott, Amgen, Astra Zeneca, BMS, Bayer, Biotronik,
as chest pain. Do not neglect symptoms. ..
• Do not interrupt cardiac follow-up. Seek advice of a cardiolo- .. Boston Scientific, Cardinal Health, CardioValve, CSL Behring, Daiichi
.. Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Johnson&Johnson,
gist promptly in case of deterioration of the CV condition. ..
.. Medicure, Novartis, Polares, OrPha Suisse, Pfizer, Regeneron, Sanofi
..
.. Aventis, Sinomed, Terumo, and V-Wave. S.W. is an unpaid member
.. of the Pfizer Research Award selection committee in Switzerland and
SARS-CoV-2 vaccines ..
Patients with prior CVD should be informed that:
.. of the Women as One Awards Committee. He is a member of the
.. Clinical Study Group of the Deutsches Zentrum für Herz Kreislauf-
..
• Vaccines are very effective therapies to prevent severe SARS- .. Forschung and of the Advisory Board of the Australian Victorian
CoV-2 infection and have been tested in large-scale randomized .. Heart Institute. He is a chairperson of the ESC Congress Program
..
trials. .. Committee and a former chairperson of the ESC Clinical Practice
• There are very few contraindications to vaccines and CVD are .. Guidelines Committee. S.W. serves as unpaid advisory board mem-
not a contraindication per se.
..
.. ber and/or unpaid member of the steering/executive group of trials
• A time delay is needed prior to vaccine therapy after a recent .. funded by Abbott, Abiomed, Amgen, Astra Zeneca, Bayer, BMS,
SARS-CoV-2 infection. ..
• The ones deemed at the highest risk should be treated first, .. Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences,
.. MedAlliance, Medtronic, Novartis, Polares, Sinomed, V-Wave, and
according to local policies. ..
.. Xeltis but has not received personal payments by pharmaceutical
.. companies or device manufacturers. He is also member of the steer-
..
.. ing/executive committee group of several investigator-initiated trials
..
Supplementary material .. that receive funding by industry without impact on his personal re-
.. muneration. E.A. reports honoraria for lectures Biosense Webster.
Supplementary material is available at European Heart Journal online. .. D.C. reports personal consulting fees from Amgen, AstraZeneca,
..
.. Bayer, Boehringer Ingelheim, and Daiichi Sankyo. J.-P.C. reports grants
Acknowledgements .. or contracts from Medtronic, BMS-Pfizer for the ATLANTIS trial;
..
The following people reviewed the document: Victor Aboyans .. payment or honoraria for lectures, presentations, speakers’ bureaus,
.. manuscript writing or educational events from BMS-Pfizer, Webmed,
(France), Stefan D. Anker (Germany), Robert A. Byrne (Ireland), A. ..
John Camm (Italy), Andrew J.S. Coats (Italy), Rudolf A. de Boer (The .. AstraZeneca, and Sanofi. T.C. reports consulting fees from Boston
..
Netherlands), Stefanie Dimmeler (Germany), Donna Fitzimons (UK), .. Scientific, Medtronic, Edwards; payment or honoraria for lectures,
Christoph Gräni (Switzerland), Christian Hamm (Germany), Richard .. presentations, speakers’ bureaus, manuscript writing or educational
..
Haynes (UK), Bernard Iung (France), Adnan Kastrati (Germany), .. events from Boston Scientific, Medtronic, Edwards; and participation
Patrizio Lancellotti (Belgium), Julinda Mehilli (Germany), Béla Merkely ... on a Data Safety Monitoring Board or Advisory Board for CERC.
(Hungary), Lis Neubeck (UK), Katja E. Odening (Switzerland), .. J.R.G.-J. receives payment or honoraria for lectures, presentations,
..
Raffaele Piccolo (Italy), Lorenz Räber (Switzerland), Tobias Reichlin .. speakers’ bureaus, manuscript writing, or educational events from
(Switzerland), Manel Sabate (Spain), P. Christian Schulze (Germany), .. Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli
..
Iain A. Simpson (UK), Lars Sondergaard (Denmark), Miguel Sousa- .. Lilly, Ferrer International, Menarini, MSD, Novartis, Novo Nordisk,
Uva (Portugal), Stefan Stortecky (Switzerland), Didier Tchétché .. Pfizer, Sanofi Aventis, and Servier outside the submitted work. T.J.G.
..
(France), and Katja Zeppenfeld (The Netherlands). Support for title .. is the editor-in-chief from the Cardiovascular Research journal. T.J.G.
page creation and format was provided by AuthorArranger, a tool
.. reports speaker fees from Merck and participation to the steering
..
developed at the National Cancer Institute. Matthieu Depuydt . committee of the COMPASS trial from the Public Health Research
Institute. H.H. reports unconditional Research Grants for University .. and Polares Medical. P.P. reports direct consulting fees from
..
of Antwerp and/or University of Hasselt from Bracco Imaging .. Boehringer Ingelheim, Pfizer, and Bayer AG and direct honoraria for
Europe, Daiichi-Sankyo, Boehringer-Ingelheim, Abbott, Medtronic,
.. lectures from Bayer AG, Bristol-Myers Squibb, Boehringer Ingelheim,
..
Biotronik, St. Jude Medical, and Fibricheck/Qompium. As EHRA presi- .. Pfizer, Sanofi, Roche, and Boston Scientific. M.R. reports research
dent 2018–2020, H.H. reports no personal honorarium for any
.. grant via his institution from Medtronic, Boston Scientific, Terumo,
..
industry-related speaker or advisory role between March 2017 and .. Biotronik, and GE Healthcare. S.R. reports research grant via his insti-
September 2020. After September 2020, H.H. reports payment or
.. tution from Actelion, AstraZeneca, Bayer, Janssen, and Novartis and
..
honoraria for lectures, presentations, speakers’ bureaus, manuscript .. remunerations for lectures from Abbott, Acceleron, Actelion, Arena,
writing, or educational events. B.I. reports other financial or non-
.. Bayer, Ferrer, Janssen, MSD, Novartis, Pfizer, United Therapeutics,
..
.. and Vifor. G.S. reports research grant via his institution from Boston

financial interests as leader for a small single-centre phase 2 RCT
..
testing the benefits of i.v. metoprolol in critically ill COVID19 .. Scientific and speaker fees from Abbott Vascular and Boston
patients. Funds from his laboratory were used, and there was no rela- .. Scientific. H.T. is the president-elect of the German Cardiac Society
..
tionship with any third party. Metoprolol is not approved for ARDS .. and is a chair of the 2020 ESC NSTE ACS Guideline. B.W. reports
(COVID or non-COVID related) and thus this trial was an initial step .. lecture fees for symposia on hypertension, unrelated to the content
..
for its repurposing. Metoprolol is out of patent and has no commer- .. of those manuscripts from Pfizer, Boehringer, Servier, and Daichi
cial interest. F.A.K. reports research grants via his institution from .. Sankyo; travel/accommodation fees to conference from Pfizer,
..
Bayer, Bristol-Myers Squibb, Boehringer-Ingelheim, MSD, Daiichi- .. Boehringer, Servier, and Daichi Sankyo. B.W. is the chair of the most
Sankyo, Actelion, the Dutch thrombosis association, The .. recent 2018 ESC–ESH Hypertension Guideline. The other authors
..
Netherlands Organisation for Health Research and Development, .. declare that there is no conflict of interest.
and the Dutch Heart foundation, all outside the current work. F.A.K. ..
.. Data availability
is a member of the Dutch guideline committee on antithrombotic ..
therapy, and the ASH guideline on thromboprophylaxis in COVID- .. No new data were generated or analysed in support of this research.
..
19 patients. F.A.K. is a member of the nucleus of the ESC Working ..
Group on RV function and pulmonary circulation. S.V.K. reports
..
..
grants or contracts via his institution from Bayer AG, Boston .. Appendix
Scientific, Servier, Actelion-Janssen, Daiichi-Sankyo; consulting fees
..
.. The Task Force for the management of COVID-19 of the
from Bayer AG, Pfizer–Bristol-Myers Squibb, Daiichi-Sankyo, and ..
Boston Scientific; payment or honoraria for lectures, presentations
.. European Society of Cardiology (ESC)
.. Writing Committee: Colin Baigent* (MRC Population Health
from Bayer AG, Pfizer–Bristol-Myers Squibb, Daiichi-Sankyo Boston ..
Scientific, and MSD Novartis. U.L. reports grants or contracts from
.. Research Unit, Nuffield Department of Population Health, Oxford,
.. UK); Stephan Windecker* (Department of Cardiology, Inselspital, Bern
Bayer and Novartis, Amgen; consulting fees from Bayer, Novartis, ..
.. University Hospital, Bern, Switzerland); Daniele Andreini (Centro
Amgen, Sanofi, and Pfizer; payment or honoraria for lectures, presen- .. Cardiologico Monzino, IRCCS, Milan, Italy and Department of
tations, speakers’ bureaus, manuscript writing or educational events ..
.. Clinical Sciences and Community Health, Cardiovascular Section,
from Bayer, Novartis, Amgen, Sanofi, and Pfizer. C.L. reports grants .. University of Milan, Milan, Italy); Elena Arbelo (Arrhythmia Section,
or contracts from Biotronik, Medtronic, Boston Scientific, Microport, ..
.. Cardiology Department, Hospital Clı́nic, Universitat de Barcelona,
and Abbott; support for attending meetings and/or travel from .. Barcelona, Spain and Institut d’Investigacions Biomèdiques August Pi i
Biotronik, Medtronic, Boston Scientific, Microport, and Abbott. M.L. ..
.. Sunyer, Barcelona, Spain and Centro de Investigación Biomédica en
reports honoraria for the role of faculty member of two webinars on .. Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
COVID-19 from a private society committed to educational initia- ..
.. and ECGen, the Cardiogenetics Focus Group of EHRA); Emanuele
tives and the Italian Association of Hospital Cardiologists. N.M. ..
reports a research grant from Getinge Global US; payment or hono- .. Barbato (Department of Advanced Biomedical Sciences, Federico II
.. University, Naples, Italy and Cardiovascular Center Aalst, OLV
raria for lectures, presentations, speakers’ bureaus, manuscript writ- ..
ing, or educational events from Bristol Myers Squibb. C.M. reports .. Hospital, Aalst, Belgium); Antonio L. Bartorelli (Centro Cardiologico
.. Monzino, IRCCS, Milan, Italy and Department of Clinical Sciences and
research support payments via his institution from Research support ..
from several diagnostic companies, the Swiss National Science .. Community Health, University of Milan, Milan, Italy and Department
.. of Biomedical and Clinical Sciences “Luigi Sacco”, University of Milan,
Foundation, the Swiss Heart Foundation; consulting fees from Idorsia; ... Milan, Italy); Andreas Baumbach (Centre for Cardiovascular Medicine
payment via his institution for his participation on a Data Safety ..
Monitoring Board or Advisory Board from Roche and from Osler.
.. and Devices, William Harvey Research Institute, Queen Mary
.. University of London and Barts Heart Centre, London, UK and Yale
A.S.P. reports consulting and proctoring payment via her institution ..
from Medtronic; consulting and proctoring payment from Boston
.. University School of Medicine, New Haven, CT, USA); Elijah R. Behr
.. (ECGen, the Cardiogenetics Focus Group of EHRA, Cardiology
Scientific; payment or honoraria for lectures, presentations, speakers’ ..
bureaus, manuscript writing, or educational events from Medtronic,
.. Clinical Academic Group, Institute of Molecular and Clinical Sciences,
.. St George’s, University of London, London, UK and St George’s
Abbott, and Boston Scientific; payment for expert testimony via her ..
.. University Hospitals NHS Foundation Trust, London, UK and
institution from Medtronic, Boston Scientific, and Abbott; and partici- .. European Reference Network for Rare and Low Prevalence
pation to the steering committee for the ongoing SMART trial. F.P. ..
.. Complex Diseases of the Heart (ERN GUARDHEART; http://guard
reports travel expenses from Abbott Vascular, Edwards Lifesciences, .. heart.ern-net.eu); Sergio Berti (U.O.C. Cardiologia Diagnostica e
..
Interventistica, Dipartimento Cardiotoracico, Fondazione Toscana G. .. Netherlands); Stavros V. Konstantinides (Center for Thrombosis and
Monasterio – Ospedale del Cuore G. Pasquinucci, Massa, Italy); .. Hemostasis, Johannes Gutenberg University Mainz, Mainz, Germany
..
Héctor Bueno (Centro Nacional de Investigaciones Cardiovasculares .. and Department of Cardiology, Democritus University of Thrace,
(CNIC), Madrid, Spain and Cardiology Department, Hospital .. Alexandroupolis, Greece); Ulf Landmesser (Department of
..
Universitario 12 de Octubre and Instituto de Investigación Sanitaria .. Cardiology, Charite University Medicine Berlin, Berlin, Germany and
Hospital 12 de Octubre (imas12), Madrid, Spain and Centro de .. Berlin Institute of Health (BIH), German Center of Cardiovascular
..
Investigación Biomédica en Red de Enfermedades Cardiovasculares .. Research (DZHK), Partner Site Berlin, Berlin, Germany); Christophe
(CIBERCV), Madrid, Spain); Davide Capodanno (Division of .. Leclercq (University of Rennes, CHU Rennes, INSERM, LTSI – UMR
..
Cardiology, A.O.U. Policlinico “G. Rodolico-San Marco” University of .. 1099, Rennes, France); Sergio Leonardi (University of Pavia, Pavia, Italy
..

Catania, Catania, Italy); Riccardo Cappato (Arrhythmia & .. and Fondazione IRCCS Policlinico S.Matteo, Pavia, Italy); Maddalena
Electrophysiology Center, IRCCS Gruppo MultiMedica, Sesto San .. Lettino (Cardio-Thoracic and Vascular Department, San Gerardo
Giovanni, Milan, Italy); Alaide Chieffo (San Raffaele Scientific Institute, .. Hospital, ASST-Monza, Monza, Italy); Giancarlo Marenzi (Centro
..
Milan, Italy); Jean-Philippe Collet (Sorbonne Université, ACTION study .. Cardiologico Monzino, IRCCS, Milan, Italy); Josepa Mauri (Institut del
group, Institut de Cardiologie, Pitié Salpêtrière Hospital (AP-HP), .. Cor, Hospital Universitari Germans Trias i Pujol, Badalona, Spain and
..
Paris, France); Thomas Cuisset (Département de Cardiologie, CHU .. Health Department of the Government of Catalonia, Barcelona,
Timone, Marseille, France and INSERM, UMR1062, Nutrition,
.. Spain); Marco Metra (Institute of Cardiology, ASST Spedali Civili di
..
Obesity and Risk of Thrombosis, Marseille, France and Faculté de .. Brescia; Department of Medical and Surgical Specialities, Radiological
Médecine, Aix-Marseille Université, Marseille, France); Giovanni de
.. Sciences and Public Health, University of Brescia, Brescia, Italy);
..
Simone (Department of Advanced Biomedical Sciences, Federico II .. Nuccia Morici (Unità di Cure Intensive Cardiologiche e De Gasperis
University, Naples, Italy and Hypertension Research Center, Federico
.. Cardio Center, ASST Grande Ospedale Metropolitano Niguarda,
..
II University Hospital, Naples, Italy); Victoria Delgado (Heart Lung .. Milan, Italy and Dipartimento di Scienze Cliniche e di Comunità,
..
Centrum, Leiden University Medical Center, Leiden, The .. Università degli Studi, Milan, Italy); Christian Mueller (Cardiovascular
Netherlands); Paul Dendale (Heart Centre Hasselt, Jessa Hospital, .. Research Institute Basel (CRIB), University Hospital Basel, Basel,
..
Hasselt, Belgium and Faculty of Medicine and Life Sciences, Uhasselt, .. Switzerland and University of Basel, Basel, Switzerland); Anna Sonia
Diepenbeek, Belgium); Dariusz Dudek (Institute of Cardiology, .. Petronio (Cardiothoracic and Vascular Department, University of Pisa,
..
Jagiellonian University Medical College, Kraków, Poland and Maria .. Ospedale cisanello, Pisa, Italy); Marija M. Polovina (Faculty of Medicine,
Cecilia Hospital, GVM Care&Research, Cotignola (RA), Ravenna, .. Belgrade University, Belgrade, Serbia and Department of Cardiology,
..
Italy); Thor Edvardsen (Department of Cardiology Oslo University .. Clinical Centre of Serbia, Belgrade, Serbia); Tatjana Potpara (School of
Hospital, Rikshospitalet, Oslo, Norway); Arif Elvan (Isala Heart .. Medicine, University of Belgrade, Belgrade, Serbia and Department
..
Center, Zwolle, The Netherlands); José R. González-Juanatey .. for Intensive Arrhythmia Care, Cardiology Clinic, Clinical Centre of
(Cardiology Department, University Hospital, IDIS, CIBERCV, .. Serbia, Belgrade, Serbia); Fabien Praz (Department of Cardiology,
..
University of Santiago de Compostela, Santiago de Compostela, .. University Hospital Bern, Bern, Switzerland); Bernard Prendergast (St
Spain); Mauro Gori (Cardiovascular Department & Cardiology Unit, .. Thomas’ Hospital and Cleveland Clinic London, London, UK); Eva
..
Papa Giovanni XXIII Hospital-Bergamo, Bergamo, Italy); Diederick .. Prescott (Department of Cardiology, Bispebjerg University Hospital,
Grobbee (Julius Global Health, the Julius Center for Health Sciences .. Copenhagen, Denmark); Susanna Price (Royal Brompton Hospital,
..
and Primary Care, University Medical Center Utrecht, Utrecht, The .. London, UK and National Heart & Lung Institute, Imperial College,
Netherlands); Tomasz J. Guzik (Institute of Cardiovascular and Medical ... London, UK); Piotr Pruszczyk (Department of Internal Medicine &
Sciences, University of Glasgow, Glasgow, UK and Department of
.. Cardiology, Medical University of Warsaw, Warsaw, Poland); Oriol
..
Medicine, Jagiellonian University College of Medicine, Kraków, .. Rodrı́guez-Leor (Centro de Investigación Biomédica en Red de
Poland); Sigrun Halvorsen (Department of Cardiology, Oslo University
.. Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain and
..
Hospital Ulleval, Oslo,Norway and University of Oslo, Oslo, .. Institut del Cor, Hospital Universitari Germans Trias i Pujol,
Norway); Michael Haude (Medical Clinic I, Städtische Kliniken Neuss,
.. Badalona, Spain); Marco Roffi (Department of Cardiology, Geneva
..
Lukaskrankenhaus GmbH, Neuss, Germany); Hein Heidbuchel .. University Hospitals, Geneva, Switzerland); Rafael Romaguera
(Department of Cardiology, University Hospital Antwerp and
.. (Servicio de Cardiologı́a, Hospital Universitario de Bellvitge-IDIBELL,
..
University of Antwerp, Antwerp, Belgium); Gerhard Hindricks .. L’Hospitalet de Llobregat, Barcelona, Spain); Stephan Rosenkranz
..
(Department of Internal Medicine/Cardiology/Electrophysiology, .. (Clinic III for Internal Medicine (Cardiology) and Cologne
Heart Center Leipzig, University Hospital Leipzig, Leipzig, Germany .. Cardiovascular Research Center (CCRC), Heart Center at the
..
and Leipzig Heart Institute (LHI), Leipzig, Germany); Borja Ibanez .. University of Cologne, Cologne, Germany and Center for Molecular
(Centro de Investigación Biomédica en Red de Enfermedades .. Medicine Cologne (CMMC), University of Cologne, Cologne,
..
Cardiovasculares (CIBERCV), Madrid, Spain and Centro Nacional de .. Germany); Andrea Sarkozy (Department of Cardiology, University
Investigaciones Cardiovasculares (CNIC), Madrid, Spain and IIS- .. Hospital Antwerp and University of Antwerp, Antwerp, Belgium);
..
Fundación Jiménez Dı́az Hospital, Madrid, Spain); Nicole Karam .. Martijn Scherrenberg (Heart Centre Hasselt, Jessa Hospital, Hasselt,
(Université de Paris, PARCC, INSERM, Paris, France and European .. Belgium and Faculty of Medicine and Life Sciences, Uhasselt,
..
Hospital Georges Pompidou, Paris, France); Hugo Katus (Department .. Diepenbeek, Belgium); Petar Seferovic (Faculty of Medicine, Belgrade
of Internal Medicine, University Hospital of Heidelberg, Heidelberg, .. University, Belgrade, Serbia and Serbian Academy of Sciences and
..
Germany); Fredrikus A. Klok (Department of Thrombosis and .. Arts, Belgrade, Serbia); Michele Senni (Cardiovascular Department &
Hemostasis, Leiden University Medical Center, Leiden, The .. Cardiology Unit, Papa Giovanni XXIII Hospital-Bergamo, Bergamo,
.. 14. Rodriguez-Leor O, Cid Alvarez AB, de Prado AP et al. In-hospital outcomes of

Italy); Francesco R. Spera (Department of Cardiology, University ..
Hospital Antwerp and University of Antwerp, Antwerp, Belgium); .. patients with ST-segment elevation myocardial infarction and COVID-19.
.. EuroIntervention 2021;16:1426–1433.
Giulio Stefanini (Department of Biomedical Sciences, Humanitas .. 15. Stefanini GG, Azzolini E, Condorelli G. Critical organizational issues for cardiol-
University, Pieve Emanuele – Milan, Italy and Humanitas Research .. ogists in the COVID-19 outbreak: a frontline experience from Milan, Italy.
.. Circulation 2020;141:1597–1599.
Hospital IRCCS, Rozzano – Milan, Italy); Holger Thiele (Leipzig Heart .. 16. Roffi M, Patrono C, Collet JP et al.; ESC Scientific Document Group. 2015 ESC
Institute (LHI), Leipzig, Germany and Department of Internal .. Guidelines for the management of acute coronary syndromes in patients pre-
..
Medicine/Cardiology, Heart Center Leipzig at University of Leipzig, .. senting without persistent ST-segment elevation: Task Force for the
Leipzig, Germany); Daniela Tomasoni (Institute of Cardiology, ASST .. Management of Acute Coronary Syndromes in Patients Presenting without
.. Persistent ST-Segment Elevation of the European Society of Cardiology (ESC).
Spedali Civili di Brescia; Department of Medical and Surgical .. Eur Heart J 2016;37:267–315.
..

Specialities, Radiological Sciences and Public Health, University of 17. Imazio M, Klingel K, Kindermann I et al. COVID-19 pandemic and troponin: in-
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.. 18. Stefanini GG, Chiarito M, Ferrante G et al.; Humanitas COVID-19 Task Force.
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M. Touyz (Institute of Cardiovascular and Medical Sciences, University .. patients with COVID-19. Heart 2020;106:1512–1518.
.. 19. Kucharski AJ, Russell TW, Diamond C et al.; Centre for Mathematical
of Glasgow, Glasgow, UK); Arthur A. Wilde (ECGen, the .. Modelling of Infectious Diseases C-wg. Early dynamics of transmission and con-
Cardiogenetics Focus Group of EHRA and European Reference
.. trol of COVID-19: a mathematical modelling study. Lancet Infect Dis 2020;20:
.. 553–558.
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Heart (ERN GUARDHEART; http://guardheart.ern-net.eu) and
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.. 21. Basille D, Plouvier N, Trouve C, Duhaut P, Andrejak C, Jounieaux V. Non-ster-
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J_ID: Customer A_ID: EHAB697 Copyedited by: Manuscript Category: Special Article Cadmus Art: OP-EHEA21070

European Heart Journal (2021) 00, 1–45 SPECIAL ARTICLE

ESC guidance for the diagnosis and

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Protective measures for healthcare personnel

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Treatment of SARS-CoV-2 infection

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If at least one criterion is fulfilled, check for exclusion criteria.

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• Age >80 years.

(2) As SARS-CoV-2 test results are not immediately available in STEMI

Management of patients with cardiogenic shock/out-of-hospital cardiac arrest

Detection of SARS-CoV-2 in respiratory specimens upon admission

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Negative Positive or suspected

Treat as usual Dedicated network

Fever or clinical sign of infection

Test for SARS-CoV-2

Patients with STEMI during COVID-19 pandemic

Type to access to care

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Transport to hospitals with At hospitals with At hospitals without

Timely primary Timely primary

Fibrinolysis Primary PCI Fibrinolysis

distress or multiorgan failure or Takotsubo. In the event any of the dif-

Patients with NSTE-ACS during COVID-19 outbreak

Very high risk High risk Intermediate risk Low risk

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Test for SARS-CoV-2

Immediate invasive Early invasive after

testing should be postponed in order not to expose these patients to

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.. 25.6 ng/L) compared to those with non-severe course.42 In add-

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Elective surgical and transcatheter interventions for VHD con-

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Self-isolated hypertensive patient

Continue treatment with antihypertensive medication according to

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Hospitalized hypertensive patient with COVID-19 infection

Unless hypotensive or there is acute kidney injury

Monitor for arrhythmias which may be more common in hypertensive

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Table 3 Categorization of electrophysiological procedures in the context of COVID-19

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AF.162,174–176 New-onset AF in sepsis and ARDS has been associated

Acute treatment of new atrial fibrillation or atrial flutter episode

Stable haemodynamic Synchronized

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Acute treatment of new episodes of ventricular tachyarrhythmias (VT/VF)

Y Stable haemodynamic status N

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.. • Normalizing potassium level (target >_4.5 mEq/L);