key: cord-0837655-8nv1a76u
authors: Dhakal, Bishnu P.; Sweitzer, Nancy K.; Indik, Julia H.; Acharya, Deepak; William, Preethi
title: SARS-CoV-2 Infection and Cardiovascular Disease: COVID-19 Heart
date: 2020-06-05
journal: Heart Lung Circ
DOI: 10.1016/j.hlc.2020.05.101
sha: 67c7fc6032aebcf1734def33ff923c43a9ab97a5
doc_id: 837655
cord_uid: 8nv1a76u

Coronavirus disease (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The symptoms of the disease range from asymptomatic to mild respiratory symptoms and even potentially life-threatening cardiovascular and pulmonary complications. Cardiac complications include acute myocardial injury, arrhythmias, cardiogenic shock and even sudden death. Furthermore, drug interactions with COVID-19 therapies may place the patient at risk for arrhythmias, cardiomyopathy and sudden death. In this review, we summarise the cardiac manifestations of COVID-19 infection and propose a simplified algorithm for patient management during the COVID-19 pandemic.

Coronavirus disease originated in the Wuhan province of China in late 2019 and is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is genetically related to the coronavirus responsible for the SARS outbreak in 2002 [1] . The infection has spread globally and was declared a pandemic by the World Health Organization (WHO) on March 11, 2020 . The number of confirmed cases and deaths continue to rise daily.

The clinical manifestations of COVID-19 may range from asymptomatic or mild respiratory symptoms to severe life threating respiratory and cardiac failure (Tables 1 and 2, Figure 1 ) [2] [3] [4] [5] [6] . Among 72,314 patients with COVID-19 in China, the clinical severity was reported as mild in 81.4%, severe in 13 .9% and critical in 4.7% of patients [2] . In a recent study from New York, the most common presenting symptoms were cough (79.4%), fever (77.1%), dyspnoea (56.5%), myalgias (23.8%), diarrhoea (23.7%), and nausea and vomiting (19.1%) [7] . The primary cause of death in COVID-19 infection is respiratory failure but cardiac manifestations may contribute to overall mortality and even be the primary cause of death in these patients (Table 3 ) [3, [7] [8] [9] [10] [11] . Concomitant cardiovascular (CV) conditions are present in 8-25% of overall COVID-19 infected population and in a higher proportion of those who die [7, 10, [12] [13] [14] [15] [16] . A meta-analysis of eight studies from China (46,248 patients) showed a higher prevalence of hypertension (17±7%) and diabetes mellitus (8±6%) followed by cardiovascular disease (5±4%) in COVID-19 patients [10] . In another analysis of 44,672 cases from Chinese Center for Disease Control and Prevention, a higher case fatality rate was noted among patients with preexisting comorbid conditions (10.5% for CV disease, 7.3% for diabetes, 6.3% for chronic respiratory disease, 6% for hypertension, and 5.6% for cancer) compared to the overall case-fatality rate of 2.3% in the entire cohort [2] . Medications used for the treatment of COVID-19 infection can also increase overall cardiovascular risk [12] .

SARS-CoV-2 contains four structural proteins, namely spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of which S protein mediates the viral entry into host cells [17, 18] . The virus exhibits strong binding to cell-associated and soluble angiotensin converting enzyme (ACE) 2 receptors expressed in many organs such as the heart, kidneys, intestine, lung, brain and liver [19, 20] . infected patients thus present with a spectrum of atypical gastrointestinal manifestations, cardiac and renal injury, neurological and acute respiratory symptoms [16, 19, 21] . In the lungs, the virus leads to endothelial and microvascular dysfunction, alveolar exudative inflammation, interstitial inflammation and fibrosis, and focal bleeding which causes severe respiratory manifestation of the disease [22] [23] [24] . Coronavirus particles has been observed in the ciliated columnar epithelial cells of bronchiolar mucosa [23] .

After gaining entry into the cells via ACE2 receptors, SARS-CoV-2 down-regulates the ACE2 expression such that the enzyme is unable to exert organ protective effects [25] . ACE inhibitors (ACEI) and angiotensin receptor blockers (ARB) upregulate the number of ACE2 receptors on the surface of myocardial, alveolar and gastrointestinal cells which has raised the concern of ACEI and ARB induced increase in COVID-19 acquisition into the myocardial and alveolar cells [19, 22, 26, 27] . However, renin angiotensin aldosterone system (RAAS) blockade has been shown to reduce the exposure to SARS-CoV-1 spike protein induced acute lung injury in experimental mouse models [19, [28] [29] [30] [31] . Similarly, a recent study showed that patients on ACEI or ARB therapy had a lower rate of severe COVID-19 disease and a trend toward a lower level of interleukin-6 (IL-6), and increased CD3 and CD8 T cell counts in the peripheral blood and a decreased peak viral load [32] . ACEI and ARB therapy may therefore be protective in low level viraemia and trials of losartan on COVID-19 patients are ongoing [9, 25, 33, 34] .

COVID-19 related immune response may be multiphasic as illustrated by Siddiqi et al. (Table 1) [4].

Similar to an influenza outbreak, myocardial injury due to COVID-19 may be related to increased viscosity, heightened coagulation cascade, pro-inflammatory effects or endothelial cell dysfunction caused by SARS-CoV-2 virus [35, 36] . In a recent study of COVID-19 patients, there was cardiomyocyte hypertrophy, degeneration and necrosis of cardiomyocytes, mild interstitial hyperaemia and oedema along with infiltration of lymphocytes, monocytes and neutrophils but no virus component in the myocardial tissue [23, 37] . In another autopsy report, there was scattered individual cell myocyte necrosis with lymphocytes adjacent to, but not surrounding, degenerating myocytes, which may represent an early manifestation of a viral myocarditis [24] . The pericytes may be infected by the SARS-CoV-2 virus and cause capillary endothelial cell or microvascular dysfunction leading to individual cell necrosis [22] [23] [24] . Myocardial injury in COVID-19 patients could be due to coronary spasm, cholesterol plaque rupture, hypoxic injury, microthrombi, or direct endothelial or vascular injury [38] . Myocardial injury and fulminant myocarditis can occur from direct viraemic effect on the myocardial cells and secondary effects from the body's hyperimmune response to the virus and overall systemic inflammatory response [9] .

Increasing levels of inflammatory markers such as C-reactive protein, D-dimer, ferritin, IL-6 and lactate dehydrogenase (LDH) has been associated with higher mortality in COVID-19 patients, possibly due to cytokine storm or secondary haemophagocytic lymphohistiocytosis [11, [39] [40] [41] [42] . SARS-CoV-2 can activate the coagulation cascade leading to thrombocytopaenia and sometimes severe hypercoagulability and its sequelae such as ischaemia of the finger and toes [10, 43, 44] . The higher incidence of venous and arterial thromboembolism despite prophylactic anticoagulation in these patients is likely due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation, and some physicians have even used tissue plasminogen activator (tPA) with some improvement in ARDS [45, 46] .

Myocardial injury, defined as elevation in cardiac troponin concentration above the 99 th percentile of upper reference limit, has been observed in 7-17% of hospitalised COVID-19 patients [10, 39, 40, [47] [48] [49] [50] . Furthermore, the incidence of myocardial injury as reported from China increases with the severity of illness, rising to 22.2% of patients needing ICU care and 59% of patients that died [10, 51] .

Acute coronary syndrome (ACS) can be one of the initial presentations of COVID-19 infection which may range from ST elevation myocardial infarction (STEMI) to Takotsubo cardiomyopathy [10, 42, 52] .

Myocardial ischaemia and infarction could be secondary to plaque rupture triggered by a virus-induced stress response or from thrombosis secondary to hypercoagulability [10, 36] . Myocardial supply-demand mismatch can cause Type 2 MI [47] . In a recent series of 18 COVID patients from New York, who had STEMI during initial presentation (n=10) or during hospitalisation (n=8), there was variability in presentation, a high prevalence of nonobstructive disease (33% of those who underwent cardiac catheterisation), and a poor prognosis (72% mortality) [42] . Acute virus-negative lymphocytic myocarditis has been associated with SARS-CoV-2 respiratory infection, with some reports showing improvement in cardiac biomarkers after treatment with lopinavir/ritonavir and hydroxycholoroquine [53, 54] . Any rise in serum troponin level should be interpreted in the context of the clinical scenario and results of further evaluation by invasive angiography or coronary computed tomography (CT) angiogram [55] . High risk patients may need admission to the hospital for further management as per clinical practice guidelines but low risk patients can be discharged from the emergency department after discussing the appropriate follow-up plan in case of recurrent symptoms [56] .

Elevated cytokine levels can lead to a systemic inflammatory response and myocardial injury, both of which can predispose to atrial and ventricular arrhythmias. New onset malignant tachyarrhythmias, such as sustained monomorphic ventricular tachycardia (VT) and polymorphic VT in the setting of elevated cardiac biomarkers, should raise the suspicion for myocarditis. In 137 patients admitted for COVID-19 disease in Hubei province, heart palpitations were noted as one of the presenting symptoms in 7.3% of patients [15, 57] . In another study of 138 hospitalised COVID-19 patients, arrhythmia was noted in 16.7% of patients and was more common in those patients admitted to intensive care unit (ICU) compared to non-ICU patients (44.4% vs. 6.9%, p <0.001) [51] . There have been reports of complete heart block and atrial fibrillation in patients with COVID-19 infection [58, 59] .

Increased inflammatory cytokines and respiratory distress can cause exacerbation of pre-existing left ventricular (LV) dysfunction or lead to a new onset cardiomyopathy. New onset LV dysfunction may represent myocarditis, stress cardiomyopathy or myocardial ischaemia, all of which increase the risk of death [10] . In a study by Zhou et al., the incidence of heart failure was significantly higher in non survivors from the infection compared to survivors (52% vs 12%, p≤0·0001) [10] . Right heart failure is likely to occur due to elevated pulmonary artery pressure from pulmonary complications [16] . In early stages, exacerbation of heart failure with preserved ejection fraction can occur due to aggressive fluid resuscitation attempts, and in the later stages of disease when cytokine levels rise, acute systolic heart failure leading to cardiogenic shock has been reported [10] .

The clinical manifestations of COVID-19 infection and medication side effects pose challenges to physicians taking care of these patients. Various antivirals, antimalarial and immunomodulating medications, glucocorticoids and convalescent plasma from recovered patients have been used for the treatment of COVID-19 with variable results (Table 5) (Table 6 ) [68] . Chloroquine and hydroxychloroquine cause alkalinisation of the intracellular phagolysosome and thus cause underglycosylation of ACE2 receptors required for cellular entry of COVID-19, which prevents virion fusion and uncoating [60, 61] . Hydroxychloroquine with or without azithromycin has been shown to decrease viral carriage in recent small studies [60] . However, there was no evidence of clinical efficacy of hydroxychloroquine in patients hospitalised for COVID-19 infection with oxygen requirement in a recent French study of 181 patients [69] . Chloroquine and hydroxychloroquine, which have been used in small studies of COVID-19 patients with variable clinical outcomes, carry a risk of prolonging the QTc interval and torsade de pointes due to blockade of the KCNH2-encoded hERG/Kv11.1 potassium channel [60, 61, 70, 71] . Electrolyte abnormalities and concomitant use of QT prolonging agents may further increase the risk of fatal arrhythmias in these high risk patients [70] . Chloroquine can also inhibit CYP2D6 which will, in turn, raise the levels of beta blockers (metoprolol and carvedilol) and thus necessitate close monitoring of blood pressure and heart rate [72] . Antiviral medications used in the treatment of COVID-19 also have side effects.

Lopinavir/ritonavir may cause bradycardia, QT and PR interval prolongation [63, 70, 73, 74] and ribavirin can affect warfarin dosing [75] . Similarly lopinavir/ritonavir can increase levels of rivaroxaban, apixaban and ticagrelor, and decrease levels of clopidogrel and prasugrel due to the interaction with cytochrome P450 enzymes [76] [77] [78] [79] . Tocilizumab and sarilumab, IL-6 receptor blockers, have shown some promising results for the treatment of cytokine release syndrome or secondary haemophagocytic lymphohistiocytosis [80] . In a recent cohort of patients hospitalised for severe COVID-19 who were treated with compassionate-use remdesivir, clinical improvement in respiratory status was observed in 68% of patients [59] . A National Institutes of Health (NIH) clinical trial also showed 31% faster recovery from advanced COVID-19 infection when treated with remdesivir [81] . When a 5-day course of remdesivir was compared with a 10-day course in phase 3 SIMPLE trial, there was similar improvement in clinical status and the side effects were nausea, elevated liver enzymes and respiratory failure [82] .

However, in another study of adult patients with severe COVID-19 infections admitted to Chinese hospitals, remdesivir was not associated with a statistically significant difference in time to clinical improvement [83] . Based on these findings, the Food and Drug Administration (FDA) has issued Emergency Use Authorization (EUA) for emergency use of remdesivir for the treatment of hospitalised COVID-19 patients. Many of the side effects of newer investigational medications are still to be evaluated [84, 85] .

The highly infectious nature of the COVID-19 infection and transmission risk to health care workers makes it challenging to manage patients with suspected or confirmed infection. Tables 2 and 3 and Figure 2 summarise a proposed diagnostic approach to a patient suspected of COVID-19 infection and management of their cardiovascular conditions. Sequential Organ Failure Assessment (SOFA) and a quick SOFA score may be helpful to assess the severity of the illness and some hospitals have used this as an initial triage tool [10, 86, 87] . There should be emphasis on minimising exposure of the health care professionals to the viral infection by performing limited bedside testing such as echocardiogram and telemetry to assess QT interval rather than a formal complete echocardiogram and electrocardiograph (ECG) [88] .

Supplemental oxygen to maintain oxygen saturation above 90%, early intubation and use of low tidal volume and high positive end expiratory pressure (PEEP) are recommended in the management of respiratory distress (Table 2, Figure 2 ) [89, 90] . Patients with COVID-19 infection require close monitoring of respiratory status with a low threshold for intubation to minimise the risk of aerosolised respiratory secretions, and prevent high-risk emergency intubations [89] . Early stages of respiratory infection can be challenging to differentiate from cardiogenic pulmonary oedema in patients with a prior diagnosis of heart failure and a serum brain natriuretic peptide (BNP) level and myocardial imaging may be helpful.

Routine right heart catheterisation should be avoided due to the potential exposure risk to health care workers (Table 3) .

Patients with COVID-19 infection are prone to fluid overload from aggressive resuscitation attempts, acute kidney injury in critically ill patients and treatment with steroids in those with chronic lung disease, and therefore require close monitoring of fluid balance and electrolytes. This is critical in very ill patients, many of whom may have new onset or worsening heart failure [89, 91] and are prone to rapid fluctuations in blood pressure and heart rate. Norepinephrine is recommended as the first line vasoactive drug in shock and vasopressin can be added if hypotension persists, although currently there is no data about their use in these patients ( (Table 3) . Hydroxychloroquine and azithromycin have a high risk of QT prolongation and drug interactions [85, 92] , and the risk associated with this combination must be reassessed. Avoiding unnecessary QT prolonging agents, monitoring electrolytes and use of isoproterenol or dopamine infusion to increase heart rate in patients with bradycardia can prevent arrhythmic complications (Table 5, Figure 3 ) [70, 92] . Tisdale and colleagues have developed a scoring system for predicting QTc prolongation in hospitalised patients which may be a useful tool to assess the risk of QTc prolongation [93] . Recent guidance from Mayo Clinic authors is that if there is QTc prolongation >500 msec or increase in QTc >60 msec after initiation of COVID-19 treatment, consideration has to be given to stop medications or reverse QTc prolonging effect [70, 94] . In another recent case report, late sodium channel blocking agents like lidocaine bolus infusion improved QTc interval in a patient with COVID-19 infection to enable treatment with hydroxychloroquine and azithromycin [92] .

infection but using caution with drug interactions and QTc prolongation [95] [96] [97] . There have been some anecdotal reports of sudden death, sinus node dysfunction and atrioventricular nodal disease in COVID-19 patients. The aetiology of such sudden death is still unclear but given the possibility of ventricular arrhythmias, prolonged ambulatory monitoring may be needed. Electrophysiology procedures such as ablation of atrial and ventricular arrhythmia should be postponed until recovery from acute illness to prevent virus transmission, unless the procedure is deemed to be lifesaving or has haemodynamic consequences as recommended by groups including the CSANZ Heart Rhythm Council COVID-19

Pandemic working group [98, 99] .

Ischaemic heart disease Primary percutaneous coronary intervention (PCI) is the recommended treatment strategy for STelevation myocardial infarction (STEMI) (Table 3, Figure 2 ) [55, 100] . Alternative therapeutic options such as systemic fibrinolytic therapy was used in China and there has been discussion among the interventional cardiology community, Society for Cardiovascular Angiography and Interventions Emerging Leader Mentorship (SCAI ELM) Members and Graduates, regarding consideration for fibrinolytic therapy in low risk STEMI patients (e.g. inferior STEMI without right ventricular involvement or lateral myocardial infarction without haemodynamic compromise) [100] . It is important for regional centres to have equitable access to thrombolytics and stock rotation systems are imperative to ensure supply [101] . Patient transfer to a higher level of care should be limited but should be performed in a timely manner when required [101] . Patients with high risk non ST-elevation MI (NSTEMI) also need urgent invasive evaluation but in low risk NSTEMI patients or in those where serum troponin level elevation is not clearly suggestive of Type 1 MI, obtaining a coronary CT angiogram can stratify the extent of coronary artery disease (CAD) and help with the decision regarding invasive coronary angiography [55] . Echocardiography and advanced imaging (e.g. magnetic resonance [MRI]) can differentiate myocarditis with diffuse myocardial dysfunction from acute coronary syndromes where a focal wall motion abnormality in the distribution of a specific coronary artery is observed (Table 3) .

Stable patients with symptoms suggestive of COVID-19 should be tested for infection prior to the procedure due to the risk of aerosol transmission to procedural staff. In patients with diagnosed COVID-19 infection, invasive procedures (e.g. intra-aortic balloon pump, pericardiocentesis, extracorporeal membrane oxygenation, temporary transvenous pacemaker, etc.) can be performed at the bedside rather than in the cardiac catheterisation laboratory to minimise the infection risk to health care workers [100, 102] . The elevation in serum troponin or BNP levels could be nonspecific in patients with COVID-19 infection, and clinicians should use their medical judgement in suspected cases of acute MI or heart failure and follow the latest recommendations from the guiding societies [16, 55] . It is also important to be mindful of delayed presentations of common cardiovascular pathology during COVID-19 pandemic as there has been a significantly reduced number of STEMI cases in the hospital and increase in out of hospital cardiac arrest [103, 104] .

Shock in COVID-19 infection could be primarily cardiogenic from acute heart failure or myocarditis but may be multifactorial, as cardiac involvement often complicates respiratory failure and sepsis [10, 49] .

Serum BNP, echocardiography and troponin level can help clarify the degree of cardiac involvement ( Figure 2 ) [105] . Routine endomyocardial biopsy and cardiac MRI to evaluate malignant arrhythmia or myocarditis should not be performed [105] . The utility of extracorporeal membrane oxygenation (ECMO) in the management of shock in COVID-19 patients is unclear [106] . Most patients with cardiogenic shock complicating COVID-19 illness die despite aggressive treatment, as one case series from China reported 83% mortality despite ECMO use [107] . It is therefore important to identify the contribution of cardiac, pulmonary and systemic causes of shock when considering mechanical respiratory and circulatory support with ECMO [108] . Evaluation by a multidisciplinary shock team consisting of an interventional cardiologist, heart failure specialist and cardiac surgeon is recommended to evaluate risks and benefits of ECMO in the individual patient [106] . Lack of sufficient health care resources during this pandemic raises ethical concerns around ECMO use and these calculations may change if effective therapies emerge [108] .

COVID-19 infection has caused a negative impact on both the physical and mental health of health workers, and many health care workers and frontline workers including firefighters have been infected with the virus [109] . Implementation of stringent infection prevention protocols may have caused delayed care in many patients and have put health care workers into difficult clinical decision making situations [109] . However, a high level of compliance (>90%) with these protocols may be required to effectively control the spread of COVID-19 infection [110] .

In a recent editorial, Allahwalla and colleagues have elegantly pointed out the long-term consequences of the COVID-19 related delay in care of chronic cardiovascular conditions and a possible second tsunami of acute cardiac conditions [104] . Therefore, there is a need for strategies to minimise, and prepare for, an impending second wave of acute medical conditions which may overwhelm the health care system and physicians [104] . Patients with cardiovascular conditions should continue to receive the health care services including preventive health services and efforts should be made to take advantage of telehealth services [101, 111] . The psychological impact of the pandemic should be taken into consideration while evaluating patients [111] . • Avoid aerosolisation. Do not disconnect from ventilator without following the precautionary steps even during code. • Avoid unnecessary transportation; encourage bedside procedure when feasible with full PPE. Abbreviation: CBC, complete blood count; CMP, complete metabolic profile; NTpBNP, N terminal pro brain natriuretic peptide; ESR, drythrocyte sedimentation rate; ICU, intensive care unit; SOFA, Sequential Organ Failure Assessment; PE, pulmonary embolism; PPE, personal protective equipment; LDH, lactate dehydrogenase; ECG, electrocardiograph; CT, computed tomography; INO, inhaled nitric oxide arrhythmia; thromboembolism and risk factor modification.

• Echocardiogram to assess LV function • Troponin trend to differentiate from Type I MI and assess prognosis along with BNP • Monitor for arrhythmia, consider EP consult if malignant arrhythmia • Inotropes and vasopressor support if haemodynamic instability with LV dysfunction.

• Discuss antiviral and anti-inflammatory therapies approved to use. • Guideline directed medical therapy for cardiomyopathy • Exercise limitation for 3-6 months to prevent sudden cardiac death.

• Address goals of care early and periodically in all patients 

• SBP<90 for >15 mins with impaired organ perfusion, Urine output <30 m/hr.

• Recognise delayed presentation of mechanical complications of myocardial infarction or peritonitis from bowel ischaemia related to low perfusion state. • Check mixed venous saturation to differentiate different types of shock.

• Conservative fluid resuscitation, crystalloid preferred over colloid.

• Norepinephrine to stabilise shock; transition to inotrope when clinically indicated.

• Inhaled pulmonary vasodilators (INO preferred) should only be administered through a closed system to prevent risk from aerosolisation.

• Evaluate alternate aetiologies of shock if haemodynamics not improving.

• Discuss with interventional cardiology regarding activating shock team.

• ECMO and mechanical circulatory support device in highly selected cases.

• Discuss with heart transplant or cardiology team regarding reducing immunosuppression especially anti metabolites due to risk of infections. • Discuss with cardiology if QTc>450 ms on a QT prolonging drug or QTc>500 ms or QTc increase after started on a QT prolonging drug.

• Assess interaction of oral anticoagulant with antivirals.

• Follow standard bradycardia guidelines (AHA, ACLS) if patient unstable.

• Discontinue AV nodal blocking agents.

• Assess interaction with antivirals (table 5) .

Abbreviations: PC, percutaneous coronary intervention; LV, left ventricle; HF, heart failure; SVT, supraventricular tachycardia; AF, atrial fibrillation; AFL, atrial flutter; EP, electrophysiology; ACLS, advanced cardiac life support; AKI, acute kidney injury; SBP, systolic blood pressure; BBB, bundle branch block; ms, milliseconds; ECMO, extracorporeal membrane oxygenation; VT, ventricular tachycardia; AHA, American Heart Association; AV, atrioventricular 

• Unnecessary, non-urgent procedures pose high risk to healthcare providers.

• Consider bedside procedures when feasible to minimize risk.

• Coronary angiogram for STEMI and high-risk NSTEMI

• Right heart catheterisation: Avoid unless necessary, e.g., HF diagnosis uncertain and clinical suspicion of mixed or refractory shock where information will change management. • No routine endomyocardial biopsy in stable patients.

• Urgent procedures only, e.g, pacemakers, ICD for secondary prevention, ablation for haemodynamically significant arrhythmia not controlled with medications or cardioversion, cardioversion for symptomatic arrhythmia, lead revision for a pacemaker dependent patient, generator change for battery at end of life for a pacemaker dependent patient. • Defer non-urgent procedures, SVT, VT ablation, AF ablation in the stable patient.

Abbreviation: MRI, magnetic resonance imaging; ICD, implantable cardioverter defibrillator; VT, ventricular tachycardia; SVT, supraventricular tachycardia; ICD, implantable cardioverter defibrillator; AF, atrial fibrillation; HF, heart failure; STEMI, ST-elevation myocardial infarction; NSTEMI, non ST-elevation myocardial infarction; CT, computed tomography; ACS, acute coronary syndrome; TTE, transthoracic echocardiogram; Abbreviations: BBB, bundle branch block; COPD, chronic obstructive pulmonary disease

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Characteristics of and important lessons from the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention

Covid-19 in critically ill patients in the Seattle Region -Case Series

COVID-19 Illness in native and immunosuppressed states: a Clinical-Therapeutic Staging Proposal J Heart Lung Transplant

Risk factors associated with Acute Respiratory Distress Syndrome and death in patients With Coronavirus Disease

Covid-19 in South Korea -challenges of subclinical manifestations

Clinical characteristics of Covid-19 in New York City

Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China

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Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China

Clinical Characteristics of Coronavirus Pneumonia 2019 (COVID-19): An Updated Systematic Review

Clinical Characteristics of Coronavirus Disease 2019 in China

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COVID-19) and cardiovascular disease

Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine

SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes. GeroScience

Trilogy of ACE2: a peptidase in the reninangiotensin system, a SARS receptor, and a partner for amino acid transporters

COVID-19, ACE2 and the cCardiovascular consequences

Neurologic features in severe SARS-CoV-2 infection

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Vander Heide RS. Pulmonary and cardiac pathology in Covid-19: the first autopsy series from New Orleans

Reninangiotensin-aldosterone system inhibitors in patients with Covid-19

Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2

Cell type-specific expression of the putative SARS-CoV-2 receptor ACE2 in human hearts

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody

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SARS-CoV2: should inhibitors of the renin-angiotensin system be withdrawn in patients with COVID-19?

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HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis

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Tissue plasminogen activator (tPA) treatment for COVID-19 associated Acute Respiratory Distress Syndrome (ARDS): A Case Series

Fourth Universal Definition of Myocardial Infarction

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Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China

Sanchis-Gomar F. Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence from a meta-analysis

Clinical characteristics of 138 hospitalized patients With 2019 novel coronavirus-infected pneumonia in Wuhan

Typical takotsubo syndrome triggered by SARS-CoV-2 infection

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Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province

Transient complete heart block in a patient with critical COVID-19

Compassionate Use of Remdesivir for Patients with Severe Covid-19

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial

In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

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A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19

Ribavirin, remdesivir, sofosbuvir, galidesivir, and tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study

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Pharmacologic treatments for Coronavirus Disease 2019 (COVID-19): A Review

Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19

No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial

Urgent guidance for navigating and circumventing the QTc prolonging and torsadogenic potential of possible pharmacotherapies for COVID-19

Hydroxychloroquine in the management of critically ill patients with COVID-19: the need for an evidence base

Influence of hydroxychloroquine on the bioavailability of oral metoprolol

Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings

Transfemoral aortic valve replacement with the repositionable Lotus Valve System in high surgical risk patients: the REPRISE I study

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Clopidogrel increases dasabuvir exposure with or without ritonavir, and ritonavir inhibits the bioactivation of clopidogrel

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Co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects

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Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial

Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase

Controversial treatments: an updated understanding of the Coronavirus Disease

Sequential organ failure assessment score is an excellent operationalization of disease severity of adult patients with hospitalized community acquired pneumonia -results from the prospective observational PROGRESS study

The Sequential Organ Failure Assessment score for predicting outcome in patients with severe sepsis and evidence of hypoperfusion at the time of emergency department presentation*. Read Online: Critical Care Medicine | Society of

CSANZ Imaging Council Position Statement on Echocardiography Services During the COVID-19 Pandemic

Management of critically ill adults with COVID-19

Formal guidelines: management of acute respiratory distress syndrome

ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America

An algorithm for managing QT prolongation in Coronavirus Disease 2019 (COVID-19) patients treated with either chloroquine or hydroxychloroquine in conjunction with azithromycin: Possible benefits of intravenous lidocaine

Development and validation of a risk score to predict QT interval prolongation in hospitalized patients

Guidance On minimizing risk of drug-induced ventricular arrhythmia during treatment of COVID-19: A Statement from the Canadian Heart Rhythm Society

AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society

ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society

AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society

Guidance for Cardiac Electrophysiology During the Coronavirus (COVID-19) Pandemic from the Heart Rhythm Society COVID-19 Task Force; Electrophysiology Section of the American College of Cardiology; and the Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology

for the Heart Rhythm Council COVID-19 Pandemic working group. Position statement on the management of cardiac electrophysiology and cardiac implantable electronic devices in australia during the COVID-19 pandemic: a living document

Considerations for Cardiac Catheterization Laboratory Procedures During the COVID-19 Pandemic Perspectives from the Society for Cardiovascular Angiography and Interventions Emerging Leader Mentorship (SCAI ELM) Members and Graduates

Rural and remote cardiology during the COVID-19 pandemic: CSANZ consensus statement

Life-threatening cardiac tamponade complicating myopericarditis in COVID-19

Elevation Myocardial Infarction Care in Hong Kong

Cardiovascular disease in the post-COVID-19 Era & the Impending Tsunami? Heart, Lung Circ

COVID-19 and acute heart failure: screening thecritically ill

Planning and provision of ECMO services for severe ARDS during the COVID-19 pandemic and other outbreaks of emerging infectious diseases

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

Preparing for the most critically ill patients with COVID-19: the potential role of extracorporeal membrane oxygenation

Cardiovascular and logistic issues associated with COVID-19 pandemic

Modelling transmission and control of the COVID-19 pandemic in Australia