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CME

COVID-19 and Cardiovascular Disease Patients

Overview

  • coronavirus disease 2019 (COVID-19) disease is an acute respiratory disease caused by an infection with a novel coronavirus SARS-CoV-2 (CDC 2020 Mar 22)
  • PubMed32201335Journal of the American College of CardiologyJ Am Coll Cardiol20200318patients with preexisting cardiovascular disease may be more susceptible to COVID-19 infection, and may be at increased risk of death, especially when patients present with elevated troponin T levels, where mortality may be three-fold higher (69.4% vs. 23%) compared to those without cardiovascular disease
  • patients who have COVID-19 may be at risk of developing cardiac complications, especially acute cardiac injury and arrhythmias; acute myocardial injury may be more common in patients with preexisting cardiovascular disease and may be associated with increased morbidity and mortality
  • clinical presentation and diagnosis of COVID-19 in patients with preexisting cardiovascular disease or COVID-19-related myocardial injury
    • diagnosis of COVID-19 may be challenging in patients with atypical presentation or preexisting cardiovascular disease
      • patients may rarely initially present with cardiovascular symptoms such as palpitations and chest tightness instead of respiratory symptoms
      • typical presenting symptoms of COVID-19 such as fatigue, dyspnea, and cough are similar to clinical presentation of preexisting cardiovascular disease such as decompensated heart failure or arrhythmias
    • myocardial injury may be defined as elevated cardiac troponin levels, elevated cardiac biomarker levels to > 99th percentile of upper reference limit, or elevated cardiac biomarker levels plus electrocardiographic and echocardiographic abnormalities
    • dyspnea with or without chest pain, elevated cardiac biomarkers, electrocardiography abnormalities, and reduced cardiac function may be common in hospitalized patients with COVID-19-related myocarditis
    • American College of Cardiology guidance: perform echocardiography in patients who experience heart failure, arrhythmia, electrocardiography changes, or cardiomegaly
  • management considerations for patients with COVID-19-related acute cardiac complications
  • considerations for use of renin-angiotensin-aldosterone system (RAAS) antagonists
    • theoretical concerns on use of RAAS antagonists in COVID-19 have been raised, generally related to angiotensin-converting enzyme-2 (ACE2) functioning as a coreceptor for entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and limited evidence of upregulation of ACE2 by RAAS antagonists
    • guidance from professional organizations, including the American College of Cardiology and European Society of Cardiology, agree on continuing RAAS antagonists in patients without COVID-19 who have a current prescription, and to not start or discontinue RAAS antagonists in patients with SARS-CoV-2 infection
  • considerations for drugs potentially used for treatment of COVID-19
    • hydroxychloroquine and azithromycin may both provoke proarrhythmia and effect of combination therapy on QT or arrhythmia has not been studied
    • to minimize arrhythmia risk when using hydroxychloroquine and/or azithromycin, perform electrocardiogram (ECG)/QT interval monitoring, correct electrolyte imbalances (hypokalemia and/or hypomagnesemia), and avoid other QTc prolonging agents if possible
    • precautions in specific patient populations may include
      • if known congenital long QT syndrome, avoiding QT-prolonging medications or careful ECG monitoring may be required
      • if severe renal insufficiency present, reduce dose of hydroxychloroquine
      • if currently using QT-prolonging medication, consider ECG monitoring
      • if electrolyte abnormalities exist, imbalances should be corrected and patients should be monitored regularly
    • if evidence of QT prolongation and/or arrhythmic toxicity during treatment
      • consider temporarily stopping use of class III antiarrhythmic medication and using alternative
      • aggressive correction of electrolyte imbalance may mitigate toxicity

General Information

Description

  • Coronavirus Disease 2019 (COVID-19) disease is an acute respiratory disease caused by an infection with novel coronavirus SARS-CoV-2 (CDC 2020 Mar 22)
  • PubMed32201335Journal of the American College of CardiologyJ Am Coll Cardiol20200318patients with preexisting cardiovascular disease
    • may be more susceptible to COVID-19 infection
    • may be at increased risk of adverse outcomes due to direct and indirect effects of COVID-19 on cardiovascular disease
    • PubMed32201335Journal of the American College of CardiologyJ Am Coll Cardiol2020051275182352-23712352Reference - J Am Coll Cardiol 2020 May 12;75(18):2352full-text

Cardiovascular presentations

  • acute cardiovascular presentations associated with COVID-19 may include
    • acute myocardial injury without obstructive coronary artery disease which may present with elevated troponin with or without additional symptoms
    • arrhythmias such as
      • atrial arrhythmias
      • ventricular tachycardia
      • ventricular fibrillation
    • acute coronary syndrome (ST-segment elevation myocardial infraction [STEMI] or non-ST segment elevation myocardial infarction [NSTEMI]) with obstructive, nonobstructive, or no coronary artery disease, which may present with
      • chest pain
      • elevated troponin
      • wall motion abnormalities
      • ST segment elevation or depression
      • T-wave abnormalities
    • heart failure with or without cardiogenic shock, which may present as
      • de novo heart failure with reduced ejection fraction (HFrEF)
      • myocarditis/myopericarditis
      • stress-induced cardiomyopathy (such as Takotsubo syndrome)
      • acute on chronic decompensated HFrEF
      • heart failure with preserved left ventricular ejection fraction (HFpEF)
      • recurrent HFrEF after previous left ventricular ejection fraction recovery
      • cytokine-mediated cardiomyopathy
    • pericardial effusion with or without tamponade
    • thromboembolic complications such as deep vein thrombosis, intracardiac thrombus, pulmonary embolism, or stroke
    • PubMed32297796CirculationCirculation20200416Reference - Circulation 2020 Apr 16 early online
  • cardiovascular presentations of patients with COVID-19 vary in case reports
    • predominantly cardiac symptoms such as chest pain and ST-segment elevation, but no fever, cough, or other symptoms suggestive of COVID-19 in case report of 64-year old woman with history of hypertension and hyperlipidemia
    • cardiogenic shock and acute respiratory distress syndrome with severe hypoxia in case report of 38-year old man with history of type 2 diabetes
    • decompensated heart failure with recurrence of left ventricular systolic dysfunction in case report of 64-year old woman with underlying nonischemic cardiomyopathy
    • symptoms typical of non-immunosuppressed patients with COVID-19 (fever, dry cough, dyspnea) in case report of 51-year old man with prior heart and kidney transplant
    • PubMed32243205CirculationCirculation20200403Reference - Circulation 2020 Apr 3 early online
  • PubMed32275347European journal of heart failureEur J Heart Fail20200410typical Takotsubo syndrome triggered by SARS-CoV-2 infection in case report of 83-year old woman with chronic hypertension hospitalized for acute chest pain (Eur Heart J 2020 May 14;41(19):1860full-text)

Prevalence of cardiovascular comorbidities in patients with COVID-19

  • PubMed32219363JAMA cardiologyJAMA Cardiol20200327prevalence of preexisting cardiovascular disease in all infections (including mild infection) reported to be 4.2% (JAMA Cardiol 2020 Mar 27 early online)
  • Study Summary
    prevalence of preexisting hypertension 17%, cardiocerebrovascular disease 16%, and diabetes 10% in hospitalized patients with COVID-19
    Details
    studySummary
    • Systematic Review based on systematic review
    • systematic review of 6 studies evaluating prevalence of cardiovascular metabolic disease in 1,527 hospitalized patients with COVID-19 in China
    • median age 34-57 years across studies and 58% male
    • prevalence of preexisting cardiovascular metabolic disease
      • hypertension 17.1% (95% CI 9.9%-24%) in analysis of 4 studies with 1,415 patients
      • cardiocerebrovascular disease 16.4% (95% CI 6.6%-26.1%) in analysis of 5 studies with 1,514 patients
      • diabetes 9.7% (95% CI 6.9%-12.5%) in analysis of 5 studies with 1,514 patients
    • PubMed32161990Clinical research in cardiology : official journal of the German Cardiac SocietyClin Res Cardiol20200311Reference - Clin Res Cardiol 2020 May;109(5):531full-text
  • Study Summary
    prevalence of preexisting hypertension 18%, cardiovascular disease 11%, and diabetes 10% in patients with confirmed COVID-19 and pneumonia in China
    Details
    studySummary
    • Systematic Review based on systematic review
    • systematic review of 31 studies evaluating 46,959 patients with confirmed COVID-19 and pneumonia in China
    • mean age 46 years across studies (mean age range 8-72 years) and 56% male overall
    • preexisting comorbidities in 35.6% (95% CI 26.7%-44.4%) in analysis of 10 studies with 1,648 patients
    • prevalence of preexisting comorbidities
      • hypertension in 18.3% (95% CI 13%-23.6%) in analysis of 12 studies with 46,317 patients
      • cardiovascular disease in 11.2% (95% CI 7.8%-14.5%) in analysis of 11 studies with 46,381 patients
      • diabetes in 10.3% (95% CI 6.9%-13.6%) in analysis of 13 studies
      • COPD in 3.9% (95% CI 1.1%-6.7%) in analysis of 8 studies with 1,614 patients
      • chronic hepatonephropathy in 3% (95% CI 2.1%-3.9%) in analysis of 7 studies with 1,392 patients
      • phthisis in 2.1% (95% CI -0.5% to 4.7%) in analysis of 3 studies with 44,745 patients
      • tumor in 1.1% (95% CI 0.3%-2%) in analysis of 8 studies with 46,267 patients
    • PubMed32161990Clinical research in cardiology : official journal of the German Cardiac SocietyClin Res Cardiol20200311Reference - J Med Virol 2020 Apr 3 early onlinefull-text
  • Study Summary
    prevalence of preexisting hypertension 31%, cardiovascular disease 14.5% and cerebrovascular disease in 5% in hospitalized patients with COVID-19 pneumonia in Wuhan, China
    Details
    studySummary
    • Cohort Study based on retrospective cohort study
    • 138 adults (median age 56 years) hospitalized with confirmed COVID-19 pneumonia in Wuhan, China evaluated
    • prevalence of most common preexisting comorbidities
      • hypertension in 31.2%
      • cardiovascular disease in 14.5%
      • diabetes in 10.1%
      • malignancy in 7.2%
      • cerebrovascular disease in 5.1%
    • PubMed32031570JAMAJAMA20200207Reference - JAMA 2020 Feb 7 early onlinefull-text, commentary can be found in JAMA 2020 Feb 5 early online
  • Study Summary
    prevalence of preexisting hypertension 15%, coronary heart disease 2.5% and cerebrovascular disease in 1.4% in patients with laboratory-confirmed COVID-19 in China
    Details
    studySummary
    • Cohort Study based on retrospective cohort study
    • 1,099 adults (median age 47 years, 58% male) with laboratory-confirmed COVID-19 between December 11, 2019 and January 29, 2020 in China evaluated
    • 23.7% had preexisting comorbidity
    • prevalence of preexisting comorbidities
      • hypertension in 15%
      • diabetes in 7.4%
      • coronary heart disease in 2.5%
      • hepatitis B infection in 2.1%
      • cerebrovascular disease in 1.4%
      • COPD in 1.1%
      • malignancy in 0.9%
      • chronic kidney disease in 0.7%
      • immunodeficiency in 0.2%
    • PubMed32031570JAMAJAMA20200207Reference - N Engl J Med 2020 Apr 30;382(18):1708full-text

Pathogenesis associated with increased risk

  • proposed pathogenesis of increased risk of COVID-19 in patients with cardiovascular disease
    • PubMed32201335Journal of the American College of CardiologyJ Am Coll Cardiol2020051275182352-23712352higher expression of angiotensin-converting enzyme 2 (ACE2) in patients with hypertension and cardiovascular disease proposed to be responsible for increased risk of COVID-19 infection as ACE2 expression in lung may be primary method of COVID-19 entry, but mechanism not fully understood and treatment implications unknown (J Am Coll Cardiol 2020 May 12;75(18):2352full-text)
    • PubMed32200663CirculationCirculation20200321other proposed mechanisms include higher prevalence of impaired immune system and older age in patients with cardiovascular disease (Circulation 2020 May 19;141(20):1648)
  • proposed mechanism for cardiovascular involvement
    • myocardial injury (defined as elevated troponin levels) may be due to myocardial ischemia or nonischemic myocardial mechanisms, including myocarditis
    • myocardial ischemia and nonischemic myocardial processes may occur in patients with severe respiratory infection and hypoxia, especially if acute respiratory distress syndrome (ARDS)
    • elevated troponin levels can be present in patients with renal insufficiency due to delayed excretion, especially if advanced disease
    • PubMed32201335Journal of the American College of CardiologyJ Am Coll Cardiol2020051275182352-23712352Reference - J Am Coll Cardiol 2020 May 12;75(18):2352full-text
  • cardiovascular complications may occur due to various mechanisms including
    • direct myocardial injury resulting from binding of SARS-CoV-2 virus to angiotensin-converting enzyme 2 (ACE2)
    • systemic inflammation causing injury to multiple organs due to high levels of proinflammatory cytokines (cytokine storm)
    • acute myocardial injury due to altered myocardial oxygen supply-demand ratio resulting from combination of hypoxia caused by respiratory illness and increased cardiometabolic demand caused by systemic infection
    • plaque rupture and coronary thrombosis
      • prothrombotic environment due to systemic inflammation
      • increased shear stress due to increased coronary blood flow
    • adverse effects of medications (such as antiviral drugs, corticosteroids, and drugs used for COVID-19 treatment such as hydroxychloroquine and azithromycin)
    • electrolyte imbalances such as hypokalemia may occur as result of systemic illness and increase risk of arrhythmia
    • PubMed32247212Diabetes & metabolic syndromeDiabetes Metab Syndr20200325143247-250247Reference - Diabetes Metab Syndr 2020 Mar 25;14(3):247

Cardiac complications of COVID-19

  • cardiovascular complications in patients with COVID-19 may include
    • arrhythmia
    • acute myocardial injury (typically defined by elevated cardiac troponin I)
    • heart failure
    • rare cardiac complications
      • left ventricular systolic dysfunction
      • acute coronary events (such as ST-segment elevation myocardial infarction)
      • cardiogenic shock
    • long-term abnormalities in cardiovascular homeostasis and lipid and glucose metabolism
    • PubMed32247212Diabetes & metabolic syndromeDiabetes Metab Syndr20200325143247-250247Reference - Diabetes Metab Syndr 2020 Mar 25;14(3):247
  • Study Summary
    14.1% incidence of acute cardiac injury in patients with confirmed COVID-19 and pneumonia in China
    Details
    studySummary
    • Systematic Review based on systematic review
    • systematic review of 31 studies evaluating 46,959 patients with confirmed COVID-19 and pneumonia in China
    • mean age 46 years across studies (mean age range 8-72 years) and 56% male overall
    • prevalence of preexisting comorbidities
      • preexisting comorbidities in 35.6% (95% CI 26.7%-44.4%) in analysis of 10 studies with 1,648 patients
      • hypertension in 18.3% (95% CI 13%-23.6%) in analysis of 12 studies with 46,317 patients
      • cardiovascular disease in 11.2% (95% CI 7.8%-14.5%) in analysis of 11 studies with 46,381 patients
      • diabetes in 10.3% (95% CI 6.9%-13.6%) in analysis of 13 studies
      • COPD in 3.9% (95% CI 1.1%-6.7%) in analysis of 8 studies with 1,614 patients
      • chronic hepatonephropathy in 3% (95% CI 2.1%-3.9%) in analysis of 7 studies with 1,392 patients
      • phthisis in 2.1% (95% CI -0.5% to 4.7%) in analysis of 3 studies with 44,745 patients
      • tumor in 1.1% (95% CI 0.3%-2%) in analysis of 8 studies with 46,267 patients
    • admission to intensive care unit required in 29.3% (95% CI 19%-39.5%) in analysis of 9 studies with 46,185 patients
    • incidence of complications
      • acute respiratory distress syndrome in 28.8% (95% CI 14.7%-42.9%) in analysis of 8 studies with 1,530 patients
      • acute cardiac injury in 14.1% (95% CI 7.9%-20.4%) in analysis of 7 studies with 1,495 patients
      • multiple organ dysfunction in 8.5% (95% CI -0.8% to 17.9%) in analysis of 4 studies with 114 patients
      • acute kidney injury in 7.1% (95% CI 3.1%-11%) in analysis of 8 studies with 1,507 patients
      • shock in 4.7% (95% CI 0.9%-8.6%) in analysis of 5 studies with 1,389 patients
    • PubMed32161990Clinical research in cardiology : official journal of the German Cardiac SocietyClin Res Cardiol20200311Reference - J Med Virol 2020 Apr 3 early onlinefull-text
  • Study Summary
    incidence of arrhythmia about 17% and acute cardiac injury about 7% in hospitalized patients with COVID-19 pneumonia
    Details
    studySummary
    • Cohort Study based on retrospective cohort study
    • 138 adults (median age 56 years) hospitalized with confirmed COVID-19 pneumonia in Wuhan, China evaluated
    • prevalence of most common preexisting comorbidities
      • hypertension in 31.2%
      • cardiovascular disease in 14.5%
      • diabetes in 10.1%
      • malignancy in 7.2%
      • cerebrovascular disease in 5.1%
    • complications
      • acute respiratory distress syndrome in 19.6%
      • arrhythmia in 16.7%
      • shock in 8.7%
      • acute cardiac injury in 7.2%
      • acute kidney injury in 3.6%
    • PubMed32031570JAMAJAMA20200207Reference - JAMA 2020 Feb 7 early onlinefull-text, commentary can be found in JAMA 2020 Feb 5 early online

Guidance from Professional Organizations

General clinical guidance for cardiovascular care team

  • American College of Cardiology (ACC) clinical guidance for cardiovascular care team
    • for preparedness
      • establish protocols for diagnosis, triage, isolation, and management of patients with cardiovascular disease or cardiovascular complications
      • train cardiovascular care team in use of personal protective equipment (PPE) in accordance with CDC guidelines
      • develop protocols specific to acute myocardial infarction (AMI), particularly related to revascularization procedures (percutaneous coronary intervention and coronary artery bypass graft surgery), including
        • limiting catheterization lab and operating room personnel to minimum
        • predetermining needs for enhanced personal protection
        • evaluating postprocedural sterilization sufficiency
        • evaluating risk-benefit of AMI interventions vs. risk of nosocomial infection
    • for patients with underlying cardiovascular (CVD) disorders
      • plan for rapid identification and isolation of CVD patients with COVID-19 symptoms
      • advise all patients with CVD of potentially increased risk of COVID-19 infection
      • patients with CVD should be vaccinated against influenza
      • consider substituting in-person visits with telemedicine (telehealth) for patients with stable CVD in geographies with active COVID-19 outbreaks to avoid risk of nosocomial COVID-19 infection
      • consider triaging COVID-19 patients for prioritization according to underlying comorbidities, including cardiovascular
      • if patient has heart failure or volume overload condition, use caution with fluid administration for viral infection and monitor carefully
    • for acute cardiac complications in patients with COVID-19
      • perform echocardiography in patients who experience heart failure, arrhythmia, ECG changes, or cardiomegaly
      • critical care teams and cardiology teams should discuss guidance of venovenous vs. venoarterial extracorporeal membrane oxygenation in patients who need extracorporeal membrane oxygenation
    • Reference - ACC 2020 Mar 6 PDF
  • PubMed32216640CirculationCirculation20200327Chinese Society of Cardiology (CSC) expert consensus on clinical management of patients with severe emergent cardiovascular disease during COVID-19 pandemic can be found in Circulation 2020 May 19;141(20):e810

Guidance on medications

Renin-angiotensin-aldosterone system antagonists and statins

  • professional organization agree on continuing RAAS antagonists in patients without COVID-19 who have current prescription, and not starting or discontinuing RAAS antagonists in patients with SARS-CoV-2 infection
    • Heart Failure Society of America/American Heart Association/American College of Cardiology (HFSA/AHA/ACC) joint statement on use of renin-angiotensin-aldosterone system (RAAS) antagonists
      • continue RAAS antagonists in patients who have current prescription for indications in which they are beneficial, such as hypertension, heart failure, or ischemic heart disease
      • in patients with cardiovascular disease who have COVID-19, do not add or remove RAAS antagonists beyond standard practice and individualize treatment decisions based on hemodynamic status and clinical presentation
      • Reference - ACC 2020 Mar 17
    • Council on Hypertension of European Society of Cardiology (ESC) strongly recommends continuation of usual antihypertensive therapy due to lack of evidence on harmful effects of ACE inhibitors or angiotensin receptor blockers in relation to COVID-19 pandemic (ESC 2020 Mar 13)
    • Canadian Cardiovascular Society (CCS) guidance on RAAS antagonists
      • patients who use ACE inhibitors, angiotensin receptor blocker, or angiotensin receptor-neprilysin inhibitor (ARNI) for heart failure or hypertension should continue medications
      • in patients with confirmed or suspected COVID-19, do not stop ACE inhibitor, ARB, or ARNI unless indicated (such as in case of symptomatic hypotension, shock, acute kidney injury, or hyperkalemia)
      • Reference - CCS 2020 Mar 20 PDF
    • National Institutes of Health (NIH) guideline on treatment of COVID-19 with RAAS antagonists and statins
      • ACE inhibitors and ARBs
        • patients with COVID-19 taking ACE inhibitors or ARBs for cardiovascular disease or other indications should continue these medications (NIH Grade AIII)
        • for treatment of COVID-19, ACE inhibitors or ARBs not recommended outside of a clinical trial (NIH Grade AIII)
      • statins
        • patients with COVID-19 taking statins for treatment or prevention of cardiovascular disease should continue these medications (NIH Grade AIII)
        • for treatment of COVID-19, statins not recommended outside of clinical trials (NIH Grade AIII)
      • Reference - NIH COVID-19 Treatment Guideline (NIH 2020 Apr 21)

Acetaminophen and aspirin

  • Canadian Cardiovascular Society (CCS) guidance
    • in patients who take low-dose aspirin for heart disease
      • continue therapy
      • confirmation or suspicion of COVID-19 not considered indication to stop aspirin
    • consider acetaminophen instead of nonsteroidal anti-inflammatory drugs in patients with heart failure or hypertension who have or are at risk of COVID-19
    • Reference - CCS 2020 Mar 20 PDF

Investigational drugs (including QTc prolonging medications) for treatment of COVID-19

  • guidance on use of drugs investigated for treatment of COVID-19, including hydroxychloroquine and chloroquine
    • American College of Cardiology/American Heart Association/Heart Rhythm Society joint statement on considerations for drug interactions
      • hydroxychloroquine and azithromycin may both provoke proarrhythmia and effect of combination therapy on QT or arrhythmia has not been studied
      • other drugs repurposed for COVID-19 treatment with known or possible risk of arrhythmia and/or cardiac arrest include
        • chloroquine associated with known risk
        • lopinavir plus ritonavir associated with possible risk
      • to minimize arrhythmia risk when using hydroxychloroquine and/or azithromycin
        • perform ECG/QT interval monitoring
          • withhold drugs in patients with baseline QT prolongation such as QTc ≥ 500 milliseconds or with known congenital long QT syndrome
          • monitor cardiac rhythm and QT interval; withdraw drug if QTc ≥ 500 milliseconds
          • consider that optimal ECG interval and rhythm monitoring may not be possible in critically ill patients
        • correct hypokalemia to > 4 mEq/L
        • correct hypomagnesemia to > 2 mEq/dL
        • avoid other QTc prolonging agents if possible
      • PubMed32267732CirculationCirculation20200408Reference - Circulation 2020 Apr 8 early online
    • PubMed32247013Heart rhythmHeart Rhythm20200401Heart Rhythm Society/American College of Cardiology/American Heart Association (HRS/ACC/AHA) guidance for cardiac electrophysiology during COVID-19
      • unknown risk of arrhythmia in patients with less severe COVID-19 illness or patients recovering from acute phase of severe illness
      • if considering use of hydroxychloroquine
        • hydroxychloroquine may cause long QT
        • clinical arrhythmia toxicity (syncope and torsade de pointes) generally related to
          • chronic use
          • use of multiple medications known to prolong QT (such as when combining with azithromycin)
          • metabolic abnormalities
          • kidney failure
          • acute overdose
        • consider precautions in specific patient populations
          • in patients with known congenital long QT syndrome, avoiding QT-prolonging medication or careful ECG monitoring may be required
          • in patients with severe renal insufficiency, reduce dose of hydroxychloroquine
          • in patients currently using QT-prolonging medication, consider ECG monitoring
          • in patients with electrolyte abnormalities (such as hypokalemia and hypomagnesemia), imbalances should be corrected and patients should be monitored regularly
      • if evidence of QT prolongation and/or arrhythmic toxicity
        • consider temporarily stopping use of class III antiarrhythmic medication and using alternative
        • aggressive correction of electrolyte imbalance may mitigate toxicity
      • PubMed32228309CirculationCirculation2020052614121e823-e831e823Heart Rhythm 2020 Apr 1 early onlinefull-text and in Circulation 2020 May 26;141(21):e823
    • European Society of Cardiology (ESC) guidance for arrhythmia and anticoagulant management in patients treated for COVID-19
      • suggested algorithm for management of patients with COVID-19 possibly treated with medications known to prolong QTc
        • COVID-19 medication known to prolong QT may be started when modifiable risk factors corrected and ECG criteria met
          • correct all modifiable risk factors for QTc prolongation
            • stop concomitant QTc-prolonging medications unless needed
            • correct hypokalemia, hypomagnesemia, hypocalcemia
            • avoid bradycardia (< 50 beats per minute
          • ECG
            • consider not having ECG prior to start of COVID-19 therapy if all of
              • recent ECG with QTc < 500 milliseconds
              • no history of structural heart disease, arrhythmia, or syncope
              • no history of acquired or congenital long QT syndrome
              • no bradycardia (< 50 beats per minute)
            • if ECG performed
              • if QTc ≥ 500 milliseconds or QTc ≥ 550 milliseconds if QRS > 120 milliseconds
                • evaluate risk-benefit of using COVID-19 medication known to prolong QT
                • use telemetry if QT-prolonging therapy started
              • if QTc < 500 milliseconds or QTc < 550 milliseconds if QRS > 120 milliseconds: start COVID-19 medication
        • after starting COVID-19 medication
          • perform ECG after 1 day or 2 doses of COVID-19 medication
            • if QTc < 500 milliseconds or change in QTc < 60 milliseconds, no further ECG needed
            • if QTc ≥ 500 milliseconds, QTc ≥ 550 milliseconds if QRS > 120 milliseconds, change in QTc ≥ 60 milliseconds, or ventricular premature beats detected, consider switching medication, lowering dose of medication, or continuation of treatment while carefully monitoring QTc and electrolyte balance
      • Cardiovascular_Disorders Hospital_MedicineFDA issues emergency use authorization permitting use of G Medical VSMS ECG Patch for remote monitoring of QT interval by electrocardiogram (ECG) in non-critically ill patients taking QT interval prolonging drugs for COVID-19 (FDA Emergency Use Authorization 2020 May 14)05/18/2020 03:31:03 PMFDA issues emergency use authorization permitting use of G Medical VSMS ECG Patch for remote monitoring of QT interval by electrocardiogram (ECG) in non-critically ill patients taking QT interval prolonging drugs for COVID-19
        • indicated for use in hospitalized patients ≥ 18 years old with COVID-19 who are not in intensive care unit and who are taking QT interval prolonging drugs (such as hydroxychloroquine, particularly in combination with azithromycin)
        • G Medical VSMS Patch is a 2-lead ECG event monitor consisting of an adhesive patch with an attached reusable recorder that is applied to patient's upper left chest
        • noncontinuous ECG data are recorded and transmitted via smartphone to company calling center, where findings are analyzed and reported to clinician
        • QT interval should be measured by standard 12-lead ECG to establish baseline and screen for existing QT prolongation before initiation of corrected QT (QTc)-interval prolonging drug therapy
        • for important precautions with use, see fact sheet for healthcare providers
        • Reference - FDA Emergency Use Authorization 2020 May 14, FDA Fact Sheet for Healthcare Providers 2020 May 14
      • retrospective evaluation of cardiovascular toxicities associated with hydroxychloroquine and azithromycin use from World Health Organization pharmacovigilance database can be found in Circulation 2020 May 22 early online
      • guidance on patients on anticoagulant therapy
        • in patients with indication for anticoagulant therapy, consider kidney function, liver function, and drug interactions between anticoagulants and therapies for COVID-19 to minimize bleeding and thromboembolic risk
        • direct (new) oral anticoagulants preferred over vitamin K antagonists in patients who are eligible for direct oral anticoagulants
        • in patients with COVID-19 on oral anticoagulation, consider switching to parenteral anticoagulation with low-molecular weight heparin or unfractionated heparin
        • do not administer azithromycin together with unfractionated heparin
      • Reference - ESC 2020 Apr 21full-text PDF

Guidance on cardiovascular-specific evaluation in patients with COVID-19

  • American College of Cardiology (ACC) guidance for evaluation in patients with COVID-19 and acute cardiac complications
    • measure troponin in patients with COVID-19 infection only if suspected acute myocardial infarction (ACC 2020 Mar 18)
    • significance of elevated natriuretic peptides is uncertain in patients with COVID-19, and natriuretic peptides should only be measured if there is clinical suspicion of acute myocardial infarction or heart failure; evaluation or treatment for heart failure may only be needed if clinical evidence exists (ACC 2020 Mar 18)
    • perform echocardiography in patients who experience heart failure, arrhythmia, ECG changes, or cardiomegaly (ACC 2020 Mar 6 PDF)
    • in patients with COVID-19 and acute myocardial injury or elevated natriuretic peptides, restrict echocardiography and coronary angiography to patients in whom procedures are expected to affect outcome (ACC 2020 Mar 18)
  • European Society of Cardiology (ESC) guidance for diagnosis of cardiovascular conditions in patients with COVID-19
    • differential diagnosis
      • presence of COVID-19 should not preclude systematic search for cardiovascular events such as acute coronary syndrome
      • consider COVID-19 infection-related injury
      • ensure that manifestations and complications of COVID-19 that mimic heart disease have been ruled out
      • if patient has COVID-19 and clinical presentation suggesting cardiovascular disease, consider
        • cardiac events that may be part of COVID-19 infection or may be unrelated, such as acute coronary syndrome, heart failure, arrhythmias, thromboembolic events, cardiogenic shock, and cardiac arrests
        • COVID-19-related cardiac injury, which may result in presentation suggestive of cardiac event
        • COVID-19 infection without cardiac injury, which may present with symptoms resembling those related to cardiac event
    • clinical presentation
      • patients with COVID-19 often present with cough, dyspnea, chest pain, and/or acute respiratory distress syndrome
      • in patients with or at risk of cardiogenic shock
        • consider mixed etiology of septic and cardiogenic shock if sepsis present
        • potential causes include large acute myocardial infarction, acute heart failure, relative hypotension or tachycardia, or COVID-19 associated myocarditis
        • diagnostic testing should include ECG, echocardiography, and coronary angiography
      • arrhythmia symptoms may be present in patients with COVID-19 and do not differ from typical clinical presentation
      • acute cardiovascular events
        • healthcare providers should be alert for cardiovascular events such as acute coronary syndrome and thromboembolic events after pneumonia and especially in patients with preexisting cardiovascular disease
    • ECG: diagnostic criteria for patients with COVID-19 similar as in general population
    • biomarkers
      • mild elevations in troponin T or I and/or natriuretic peptides in patients with COVID-19 may be caused by preexisting cardiovascular disease or COVID-19 associated acute cardiac injury
      • in patients with COVID-19 measurement of cardiac troponins (I or T) suggested only in patients with clinical suspicion of type 1 myocardial infarction or with new onset left ventricular dysfunction
      • if mild elevations in troponins and/or natriuretic peptides (such as 2-3 times the upper limit of normal values) but chest pain and/or ischemic ECG changes absent, typical workup for myocardial infarction not required
      • d-dimer concentration suggested to only measure if clinical suspicion of pulmonary embolism
    • noninvasive imaging
      • do not perform routine cardiac imaging in patients with suspected or confirmed COVID-19, but only if results are likely to impact management
      • re-evaluate which imaging modality is best for patients in both diagnostic yield and infectious risk
      • transthoracic and transesophageal echocardiography
        • echocardiography (transesophageal, transthoracic, or stress) should be avoided if results are unlikely to impact management
        • critical care echocardiography, focused cardiac ultrasound (FOCUS) and point of care ultrasound (POCUS) considered effective for screening for cardiovascular complications
      • computed tomography (CT)
        • cardiac CT should be avoided if results are unlikely to impact management
        • coronary CT angiography may be preferred noninvasive modality for diagnosis of coronary artery disease (CAD)
        • cardiac CT may be preferred over transesophageal echocardiography to rule out left atrial appendage and intracardiac thrombus before cardioversion
        • chest CT recommended in patients with respiratory distress to evaluate for COVID-19 and differentiate from other causes such as heart failure and pulmonary embolism
        • if contrast needed, kidney function should be evaluated
      • nuclear cardiology should only be performed if no other modalities can be performed, and only in specific indications
      • cardiac magnetic resonance (CMR)
        • preferred modality if suspected myocarditis in patients with known or suspected COVID-19
        • shortened CMR protocols should be used
        • if contrast needed, kidney function should be evaluated
    • Reference - ESC 2020 Apr 21PDF

Guidance on management of patients with cardiovascular disease during COVID-19 pandemic

  • European Society of Cardiology (ESC) guidance for general strategies to manage cardiovascular conditions during COVID-19 pandemic
    • elective hospitalizations should be reduced to
      • increase capacity for patients with COVID-19
      • reduce exposure of patients needing elective procedures to hospital and surroundings
      • reduce exposure of health workers to possibly asymptomatic COVID-19 patients
    • suggested categorization of (conditions for) invasive cardiac procedures during COVID-19 pandemic
      • emergency procedures that should not be postponed
        • ischemic heart disease: ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction in patients at very high risk and high risk, cardiogenic shock
        • heart failure: mechanical circulatory support for cardiogenic shock if patients < 65 years old
        • arrhythmias: pacemaker implantation for symptomatic atrioventricular block or symptomatic sinus node dysfunction with asystolic pauses
        • valvular heart disease: valve repair or replacement for acute failing valve (native or prosthetic) causing shock, surgery for aortic dissection or cardiovascular trauma, surgical aortic valve replacement (SAVR) in selected decompensated patients, or balloon aortic valvuloplasty as bridge to transcatheter aortic valve implantation (TAVI)
        • pericardiocentesis in patients with cardiac tamponade
      • urgent procedures that should be performed within days
        • ischemic heart disease: NSTEMI in patients with intermediate risk, unstable angina, left main percutaneous coronary intervention (PCI), PCI of last remaining vessel, decompensated ischemic heart failure, class IV angina, or coronary artery bypass graft surgery (CABG) in patients with NSTEMI who are unsuitable for PCI
        • heart failure: urgent heart transplant
        • arrhythmias: implantable cardioverter defibrillator (ICD) implantation in cardiac arrest of ventricular tachycardia with syncope, catheter ablation for recurrent ventricular tachycardia/ventricular fibrillation refractory to therapy, catheter ablation for atrial fibrillation with Wolff-Parkinson-White syndrome plus rapid preexcited ventricular rates, lead extraction in infective endocarditis, or battery replacement for end-of-life pacing dependency
        • valvular heart disease: TAVI for decompensated aortic stenosis, transcatheter mitral valve repair (if unsuitable for surgery) or mitral valve surgery in hemodynamically unstable patients with acute mitral regurgitation, mitral or aortic regurgitation in patients with infective endocarditis, high risk of embolism in patients with infective endocarditis, or surgery for left atrial myxoma
      • lower priority procedures that should be performed in < 3 months
        • ischemic heart disease: advanced coronary artery disease with NYHA class III or angina class III symptoms, staged PCI of nonculprit lesions in STEMI, or PCI for proximal left coronary artery disease
        • heart failure: left ventricular assist device
        • arrhythmias: catheter ablation for treatment-resistant atrial fibrillation plus fast ventricular rate
        • valvular heart disease: TAVI/SAVR in patients with severe aortic stenosis with aortic valve area < 0.6 cm2 and mean transvalvular gradient > 60 mm Hg, TAVI/SAVR in symptomatic patients with low-flow low-gradient aortic stenosis (left ventricular ejection fraction < 50%), or transcatheter mitral valve repair or mitral valve surgery in patients with mitral regurgitation and congestive heart failure who cannot be stabilized
        • biopsies
      • elective procedures that may be postponed > 3 months
        • ischemic heart disease: interventions for chronic total occlusions, chronic coronary syndrome with class II angina ot NYHA
        • arrhythmias: elective ablation and cardiac device implantation
        • valvular heart disease: TAVI/SAVR for symptomatic severe aortic stenosis with aortic valve area < 1 cm2 and mean transvalvular gradient > 40 mm Hg, TAVI/SVAR for symptomatic paradoxical low-flow low-gradient aortic stenosis (left ventricular ejection fraction > 50%), or mitral valve surgery or transcatheter mitral valve repair for secondary mitral regurgitation with stable heart failure
        • left atrial appendage closure in stable patients
        • atrial septal defect closure
        • patent foramen ovale closure
        • right heart catheterization
        • invasive evaluation of dilated cardiomyopathy
        • alcohol septal ablation in hypertrophic cardiomyopathy
    • Reference - ESC 2020 Apr 21full-text PDF
  • ESC guidance for management of specific cardiovascular conditions during COVID-19 pandemic
    • for patients with non-ST-segment elevation myocardial infarction (NSTEMI) during COVID-19 pandemic, strategy depends on risk category
      • if considered very high risk
        • perform immediate invasive strategy following regular STEMI management pathway
        • very high risk defined as any of
          • hemodynamic instability or cardiogenic shock
          • recurrent or ongoing chest pain refractory to medical therapy
          • life-threatening arrhythmia or cardiac arrest
          • mechanical complications of myocardial infarction
          • acute heart failure
          • recurrent intermittent ST-segment elevation
      • if considered high risk, defined as established diagnosis of NSTEMI based on troponins plus either dynamic ST/T changes and/or recurrent symptoms
        • test for COVID-19 and transfer to COVID-19 equipped hospital for invasive strategy if positive
        • perform early invasive strategy < 24 hours after admission if possible
      • if considered intermediate risk, defined as established diagnosis of NSTEMI plus ≥ 1 of: diabetes or renal insufficiency, ejection fraction < 40% or congestive heart failure, and early post-infarction angina or prior percutaneous intervention of coronary artery bypass surgery
        • test for COVID-19 and transfer to COVID-19 equipped hospital for invasive strategy if positive
        • consider alternative diagnosis to type 1 myocardial infarction, such as type II myocardial infarction, myocarditis, or myocardial injury due to respiratory distress, multiorgan failure, or Takotsubo syndrome
        • consider noninvasive strategy, favoring use of cardiac computed tomography angiography if equipment and expertise available
      • if considered low risk, defined as not falling in other risk categories
        • test for COVID-19
        • use noninvasive strategy
      • see also acute coronary syndromes for general management of NSTEMI
    • for patients with ST-segment elevation myocardial infarction (STEMI)
      • consider all patients with STEMI as positive for COVID-19
      • test for COVID-19 as soon as possible after first medical contact and at latest upon admission to intensive care unit
      • consider immediate complete revascularization if indicated and appropriate to avoid staged procedures
      • see ST-elevation myocardial infarction (STEMI) for general management of STEMI
    • for patients with cardiogenic shock or cardiac arrest
      • invasive coronary angiography remains essential for treatment, but considerations needed to minimize risk of nosocomial infection
      • test for COVID-19 upon admission
      • consider all patients positive for COVID-19 until test results available
        • if negative for COVID-19, treat as usual, but retest for COVID-19 if fever develops or clinical signs of infection develop
        • if positive or suspected positive for COVID-19
          • consider being more restrictive with mechanical circulatory support (MCS) and consider risk of coagulopathy associated with COVID-19 infection
          • if MCS required, extracorporeal membrane oxygenation is preferred for temporary MCS
          • consider need for specific management for acute lung injury, such as prone positioning
      • see also topics on cardiogenic shock, cardiac arrest and mechanical circulatory support
    • for patients with suspected acute heart failure
      • acute heart failure may complicate course of COVID-19 and diagnosis is essential
      • underlying mechanisms of acute heart failure in patients with COVID-19 may include acute myocardial ischemia, infarction, or myocarditis, acute respiratory distress syndrome (ARDS), acute kidney injury and hypervolemia, stress-induced cardiomyopathy, or tachyarrhythmia
      • consider for diagnosis
        • clinical presentation
        • pre-existing cardiovascular comorbidities
        • chest imaging findings
        • elevated natriuretic peptide levels
        • transthoracic echocardiography, but consider potential risk of contamination
      • management of acute heart failure may proceed as usual irrespective of COVID-19 status
      • see also acute heart failure for general management
    • for patients with suspected myocarditis
      • should be suspected in patients with COVID-19 and
        • acute-onset chest pain, ST-segment changes, cardiac arrhythmia, and hemodynamic instability
        • acute heart failure and/or cardiogenic shock without pre-existing cardiovascular disorder
      • for evaluation, cardiac computed tomography angiography is preferred to rule out coronary artery disease, cardiac magnetic resonance may be used, and endomyocardial biopsy should not be used
      • no specific treatment of myocarditis recommended in patients with COVID-19
      • see also myocarditis for general treatment
    • for patients with hypertension
      • change in treatment with ACE inhibitors and/or angiotensin receptor blockers not indicated
      • management should follow existing guideline recommendations with no change during COVID-19 pandemic
      • for self-isolated patients on hypertension treatment
        • patients should continue monitoring of blood pressure at home if possible
        • routine clinical check-up at clinic not needed during COVID-19 pandemic
      • for patients with hypertension hospitalized for COVID-19
        • consider withdrawing antihypertensive medication temporarily in patients who develop hypotension or cute kidney injury
        • consider monitoring for arrhythmias and checking plasma potassium levels
        • if invasive ventilation required, parenteral administration of antihypertensive medication typically only needed if patient develops persistent severe hypertension
      • see also hypertension for general management
    • for pulmonary embolism (PE)
      • consider prophylactic anticoagulation in all patients hospitalized with COVID-19
      • PE may be considered in patients with COVID-19 if
        • unexpected respiratory worsening
        • new or unexplained tachycardia
        • fall in blood pressure that is not due to tachyarrhythmia
        • hypovolemia or sepsis
        • ECG changes are suggestive of PE
        • signs of deep vein thrombosis
      • if PE confirmed, manage according to current guidelines based on PE risk stratification irrespective of COVID-19 infection
      • see also pulmonary embolism for general management of PE
    • for patients with arrhythmias and cardiac implantable devices
      • consider remote monitoring and postpone elective procedures as much as possible
      • in hospitalized patients
        • with atrial fibrillation and/or atrial flutter without hemodynamic instability, consider discontinuation of antiarrhythmic drugs and initiating rate control therapy
        • who are critically ill, with hemodynamic instability due to ventricular tachycardia/ventricular fibrillation or atrial fibrillation/atrial flutter, IV amiodarone is preferred antiarrhythmic drug, but combined use with hydroxychloroquine and azithromycin should be avoided
        • consider risk of Torsades de Pointes if using QT-prolonging medications for treatment of COVID-19, especially when combined with antiarrhythmic drugs, electrolyte abnormalities, renal dysfunction, and/or bradycardia
        • if Torsades de Pointes occurs, withdraw all QT-prolonging medications, target potassium level > 4.5 mEq/L, administer IV magnesium, and increase heart rate
        • consider echocardiography to evaluate ventricular function and myocardial involvement in patients with new malignant ventricular arrhythmias that are not associated with QT prolongation
      • after recovery from COVID-19, re-evaluate management in patients with atrial flutter/atrial fibrillation, including medication for rate control, rhythm control, longterm anticoagulation based on CHA2DS2-VAC score, and need for permanent pacing, catheter ablation, and/or implantable cardiac defibrillator/wearable defibrillator
      • see also topics on ventricular tachycardia and supraventricular tachycardia
    • Reference - ESC 2020 Apr 21full-text PDF

Additional guidance on cardiovascular management

  • PubMed32247013Heart rhythmHeart Rhythm20200401Heart Rhythm Society/American College of Cardiology/American Heart Association (HRS/ACC/AHA) guidance for cardiac electrophysiology during COVID-19 pandemic can be found in Heart Rhythm 2020 Apr 1 early onlinefull-text and in Circulation 2020 May 26;141(21):e823
  • Spanish Society of Cardiology Interventional Cardiology and Heart Rhythm Association consensus document on invasive cardiac procedures during COVID-19 pandemic can be found at Rec Int Card 2020 Mar 20 early online
  • PubMed32242891European heart journal cardiovascular ImagingEur Heart J Cardiovasc Imaging20200403European Association of Cardiovascular Imaging (EACVI) recommendations for cardiac imaging on precautions, indications, prioritization, and protection for patients and healthcare personnel can be found in Eur Heart J Cardiovasc Imaging 2020 Jun 1;21(6):592full-text
  • cardiac computed tomography (CT) and nuclear medicine
    • PubMed26272851Journal of cardiovascular computed tomographyJ Cardiovasc Comput Tomogr2015110196475-92475Society of Cardiovascular Computed Tomography (SCCT) guidance for use of cardiac computed tomography (CT) during COVID-19 pandemic can be found in J Cardiovasc Comput Tomogr 2020 Mar;14(2):101full-text
    • PubMed32415626Journal of nuclear cardiology : official publication of the American Society of Nuclear CardiologyJ Nucl Cardiol20200515 American Society of Nuclear Cardiology/Society for Nuclear Medicine and Molecular Imaging (ASNC/SNMMI) information statement on guidance and best practices for
    • PubMed32296886European journal of nuclear medicine and molecular imagingEur J Nucl Med Mol Imaging20200415International Atomic Energy Agency (IAEA) international expert panel-based guidance for nuclear medicine departments during COVID-19 pandemic can be found in Eur J Nucl Med Mol Imaging 2020 Jul;47(7):1615full-text
  • echocardiography
    • American Society of Echocardiography (ASE) statement on protection of patients and echocardiography service providers during COVID-19 pandemic can be found at ASE 2020 Apr 1 PDF
    • British Society of Echocardiography (BSE) guidance on echocardiography during COVID-10 pandemic can be found at BSE 2020 Apr 2
  • cardiac catheterization
    • PubMed32199938Journal of the American College of CardiologyJ Am Coll Cardiol20200316American College of Cardiology/Society of Cardiovascular Angiography and Intervention (ACC/SCAI) guidance on catheterization laboratory considerations during COVID-19 pandemic can be found in J Am Coll Cardiol 2020 May 12;75(18):2372
    • PubMed32212409Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & InterventionsCatheter Cardiovasc Interv20200325Society of Cardiovascular Angiography and Intervention Emerging Leader Mentorship (SCAI ELM) members and graduates perspectives on cardiac catheterization during COVID-19 pandemic can be found in Catheter Cardiovasc Interv 2020 Mar 25 early online
    • PubMed32223063Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & InterventionsCatheter Cardiovasc Interv20200329Italian Society of Interventional Cardiology (GISE) position paper on cath lab-specific preparedness for healthcare providers can be found in Catheter Cardiovasc Interv 2020 Mar 29 early onlinefull-text
  • triage
    • American College of Surgeons (ACS) guidance for triage of cardiac surgery patients can be found at ACS 2020 Mar 24 PDF
    • PubMed32199938Journal of the American College of CardiologyJ Am Coll Cardiol20200316American College of Cardiology/Society of Cardiovascular Angiography and Intervention (ACC/SCAI) consensus statement on triage for patients referred for structural heart disease interventions during COVID-19 pandemic can be found in JACC Cardiovasc Interv 2020 Apr 3 early online
  • advanced support
    • PubMed32358232ASAIO journal (American Society for Artificial Internal Organs : 1992)ASAIO J20200430American Society for Artificial Internal Organs (ASAIO) recommendations on advanced pulmonary and cardiac support of COVID-19 patients can be found in ASAIO J 2020 Apr 30 early onlinefull-text
    • PubMed32270695CirculationCirculation20200409American Heart Association/American Academy of Pediatrics/American Association for Respiratory Care/American College of Emergency Physicians/Society of Critical Care Anesthesiologists/American Society of Anesthesiologists (AHA/AAP/AARC/ACEP/SCCA/ASA) interim guidance on basic and advanced life support in adults, children, and neonates with suspected or confirmed COVID-19 can be found in Circulation 2020 Apr 9 early online
  • PubMed32363905CirculationCirculation20200502American Heart Association (AHA) temporary emergency guidance on STEMI systems of care can be found in Circulation 2020 May 2 early online

Considerations for Patients Treated with ACE Inhibitors and ARBs

  • background for the clinical interest on use of renin-angiotensin-aldosterone (RAAS) antagonists (angiotensin-converting enzyme [ACE] inhibitors or angiotensin receptor blockers [ARBs]) in patients with COVID-19 (coronavirus disease 2019)
  • origins of theoretical concerns with using RAAS antagonists in COVID-19
    • ACE inhibitors reported to affect expression of ACE2 in kidney and heart tissue in animal model
    • some concern about use of ACE inhibitors might relate to confusion of ACE inhibitors with ACE2 inhibitors
      • ACE and ACE2 are distinctly separate enzymes with different active sites
      • overlapping effects (if any) would be limited to indirect effects relating to effects on substrates for these enzymes
      • these indirect effects considered unlikely to influence SARs-COV-2 binding
    • ARBs reported to upregulate ACE2 in some experimental studies; weaknesses and limitations of these studies include
      • variation in study findings, particularly by individual ARB and effects on different organ types
      • effects observed at generally high ARB doses
      • no clear evidence to support facilitation of SARS-CoV-2 entry in human cells by ARBs
    • PubMed32208987Hypertension (Dallas, Tex. : 1979)Hypertension202006017561382-13851382Reference - Hypertension 2020 Jun;75(6):1382
  • potential benefits of using ARBs in COVID-19
    • the SARS-CoV-2 virus is reported to down-regulate ACE2
    • since ACE2 degrades angiotensin II, down-regulation of ACE2 may result in increased angiotensin II levels
    • increased angiotensin II levels might contribute to lung injury by increasing alveolar permeability
    • increased ACE2 expression by ARB therapy might therefore exert protective effects by decreasing lung injury caused by angiotensin II
    • PubMed32227760The New England journal of medicineN Engl J Med20200423382171653-16591653References - N Engl J Med 2020 Apr 23;382(17):1653full-text, Hypertension 2020 Jun;75(6):1382
  • considerations for patients asking for changes in antihypertensive medications medication regimens
    • though there is an absence of clear evidence to support discontinuing (or initiating) ACE inhibitors and/or ARBs in the setting of COVID-19, some patients may request changes to their medication regimens
    • clinicians and patients must acknowledge that changes to medication regimens may require
      • dose titration and increased blood pressure monitoring
      • trips to pharmacy and/or trips for blood testing, which may increase exposure and risk for infection
    • risk considerations associated with withdrawal of RAAS antagonists
      • patients with cardiovascular disease may have particularly severe COVID-19 disease; myocardial stress, myocardial injury, and cardiomyopathy may develop in some patients
      • RAAS antagonists are known to protect myocardium and kidney in patients with cardiovascular disease, and RAAS antagonist withdrawal may result in clinical decompensation in some patients (particularly those at highest cardiovascular risk)
      • RAAS antagonist withdrawal
        • may be considered riskiest in patients with guideline-directed indications (such as ACE inhibitors for heart failure or acute myocardial infarction)
        • in patients without guideline directed indication (such as use in hypertension in otherwise healthy patient) could lead to blood pressure instability when transitioning to another drug and may be associated with increased cardiovascular risk
        • may be of concern since COVID-19 reported to be associated with increased RAAS activation
    • PubMed32227760The New England journal of medicineN Engl J Med20200423382171653-16591653Reference - N Engl J Med 2020 Apr 23;382(17):1653
    • clinicians should provide reassurance to patients of the absence of data to support changes in medication regimens involving ACE inhibitors or ARBs in the context of COVID-19 (JAMA 2020 Mar 24 early online)
  • clinical trials evaluating possible role of recombinant ACE2 or ARBs
    • randomized controlled trial evaluating use of recombinant human angiotensin converting enzyme 2 (rhACE2) in patients with COVID-19 (NCT04287686)
    • randomized controlled trial evaluating use of oral losartan in patients with COVID-19 requiring hospitalization (NCT04312009)
    • randomized controlled trial evaluating use of oral losartan in patients with COVID-19 not requiring hospitalization (NCT04311177)
  • see Guidance from Professional Organizations for recommendations on use of ACE inhibitors and ARBs in the context of COVID-19 disease
  • Study Summary
    use of ACE inhibitors or ARBs does not appear to be associated with risk of positive test for SARS-CoV-2 infection or severe COVID-19 disease
    DynaMed Level2
    Details
    Cardiovascular_Disordersuse of ACE inhibitors or ARBs does not appear to be associated with risk of positive test for SARS-CoV-2 infection or severe COVID-19 disease (Ann Intern Med 2020 May 15 early online)05/26/2020 11:09:19 AMstudySummary
    • Systematic Review based on systematic review of observational studies
    • systematic review of 19 observational studies assessing association between use of ACE inhibitors or ARBs and COVID-19 in > 23,000 adults with COVID-19
    • no meta-analyses performed
    • no significant associations found between use of ACE inhibitors or ARBs and
      • positive SARS-CoV-2 tests in 2 retrospective cohort studies (one summarized here) and 1 case-control study with 8,766 patients with COVID-19
      • severity of disease in 13 retrospective cohort studies and 1 case-control study with 23,656 patients with COVID-19
    • PubMed32422062Annals of internal medicineAnn Intern Med20200515Reference - Ann Intern Med 2020 May 15 early online
  • Study Summary
    use of ACE inhibitors or ARBs does not appear to increase risk of positive test for COVID-19 or severe disease
    Details
    Cardiovascular_Disorders Hospital_Medicine Internal_Medicineuse of ACE inhibitors or ARBs does not appear to increase risk of positive test for COVID-19 or severe disease (N Engl J Med 2020 May 1 early online)05/07/2020 09:16:43 AMstudySummary
    • Cohort Study based on retrospective population-based cohort study
    • 12,594 adults who had COVID-19 test at 1 center in New York, New York from March 1 to April 15, 2020, were assessed for use of antihypertensives
      • 18.4% were taking ACE inhibitor or ARBs
      • 34.6% had hypertension
    • propensity score for likelihood of treatment with antihypertensive medications was calculated for each patient based on clinical and demographic factors
    • comparing use of ACE inhibitors vs. no use in propensity-matched analysis of patients with hypertension
      • positive test for COVID-19 in 61.2% vs. 61.1% (not significant) in analysis of 1,908 patients
      • severe COVID-19 disease in 23.8% vs. 27.1% (not significant) in analysis of 1,167 patients
    • comparing use of ARBs vs. no use in propensity-matched analysis of patients with hypertension
      • positive test for COVID-19 in 59.5% vs. 57.9% (not significant) in analysis of 2,114 patients
      • severe COVID-19 disease in 25.6% vs. 25.5% (not significant) in analysis of 1,241 patients
    • consistent results comparing use of ACE inhibitors to no use and use of ARBs to no use in propensity-matched analyses including patients without hypertension
    • consistent results for use vs. no use of other antihypertensives (beta-blockers, calcium channel blockers, and thiazide diuretics)
    • PubMed32356628The New England journal of medicineN Engl J Med20200501Reference - N Engl J Med 2020 May 1 early online
  • Study Summary
    use of ACE inhibitors and ARBs may not be associated with increased rates of COVID-19
    Details
    Cardiovascular_Disorders Hospital_Medicine Internal_Medicineuse of ACE inhibitors and ARBs may not be associated with increased rates of COVID-19 (N Engl J Med 2020 May 1 early online)05/07/2020 09:17:36 AMstudySummary
    • Case-Control Study based on population-based case-control study
    • 6,272 adults (mean age 68 years) with COVID-19 and 30,759 matched controls (mean age 68 years) without COVID-19 in Italy were assessed for use of ACE inhibitors, ARBs, and other antihypertensives
      • cases were matched to controls by sex, age, and municipality of residence in Italy from February 21, 2020 to March 11, 2020
      • 23.9% of patients with COVID-19 and 21.4% of controls had ACE inhibitors
      • 22.2% of patients with COVID-19 and 19.2% of controls had ARBs
      • 30.1% of patients with COVID-19 and 21.7% of controls had cardiovascular disease
    • no significant association between COVID-19 and use of
      • ACE inhibitors (adjusted odds ratio 0.96, 95% CI 0.87-1.07)
      • ARBs (adjusted odds ratio 0.95, 95% CI 0.86-1.05)
    • consistent results in subgroups by severity of disease (mild-to-moderate and severe/fatal), age (< 60 years and ≥ 60 years), and sex
    • consistent results for use of other antihypertensives
    • Reference - N Engl J Med 2020 May 1 early online
  • Study Summary
    use of RAAS inhibitors does not appear to be associated with COVID-19 requiring hospitalization
    Details
    Cardiovascular_Disordersuse of RAAS inhibitors does not appear to be associated with COVID-19 requiring hospitalization (Lancet 2020 May 14 early online)05/26/2020 11:10:07 AMstudySummary
    • Cohort Study based on population-based case-control study
    • 1,139 adults (mean age 69 years) hospitalized with COVID-19 and 11,390 matched controls (mean age 69 years) who were hospitalized but did not have COVID-19 in Spain were assessed for use of RAAS inhibitors (ACE inhibitors and ARBs)
      • cases were matched to controls by age, sex, region, and date of hospital admission from March 1 to March 24, 2020
      • 44% of patients with COVID-19 and 34% of controls used any RAAS inhibitor
      • 21% of patients with COVID-19 and 19% of controls used ACE inhibitors
      • 21% of patients with COVID-19 and 14% of controls used ARBs
      • 27% of patients with COVID-19 and 21% of controls had cardiovascular disease
    • no significant associations between COVID-19 requiring hospital admission and use of
      • any RAAS inhibitor (adjusted odds ratio [OR] 0.94 (95% CI 0.77–1.15)
      • ACE inhibitors (adjusted OR 0.8, 95% CI 0.64–1)
      • ARBs (adjusted OR 1.1, 95% CI 0.88–1.37)
    • consistent results in subgroups by severity of disease, age (< 70 years and ≥ 70 years), sex, and cardiovascular comorbidities
    • PubMed32416785Lancet (London, England)Lancet20200514Reference - Lancet 2020 May 14 early online

Myocardial Injury

Definition and Incidence

  • myocardial injury may be defined across studies as any of the following
    • elevated troponin levels
    • elevated cardiac biomarker levels to > 99th percentile of upper reference limit
    • elevated cardiac biomarker levels plus electrocardiographic and echocardiographic abnormalities
    • Reference - J Am Coll Cardiol 2020 Mar 18 early online
  • PubMed32200663CirculationCirculation20200321incidence of fulminant myocarditis unknown (Circulation 2020 Mar 21 early online)
  • Study Summary
    8%-12% incidence of acute cardiac injury in hospitalized patients with COVID-19 in China
    Details
    studySummary
    • Systematic Review based on systematic review
    • systematic review of 6 cohort studies evaluating prevalence of cardiovascular metabolic disease in 1,527 hospitalized patients with COVID-19 in China
    • median age 34-57 years across studies and 58% male
    • prevalence of preexisting cardiovascular metabolic disease
      • hypertension 17.1% (95% CI 9.9%-24%) in analysis of 4 studies with 1,415 patients
      • cardiocerebrovascular disease 16.4% (95% CI 6.6%-26.1%) in analysis of 5 studies with 1,514 patients
      • diabetes 9.7% (95% CI 6.9%-12.5%) in analysis of 5 studies with 1,514 patients
    • acute cardiac injury on lab results
      • 8% (95% CI 4.1%-12%) in analysis of 2 studies with 179 patients and cardiac injury defined as elevated cardiac troponin I/T
      • 11.5% (95% CI 7.8%-15.2%) in analysis of 2 studies with 1,198 patients and cardiac injury defined as elevated creatinine kinase
    • PubMed32161990Clinical research in cardiology : official journal of the German Cardiac SocietyClin Res Cardiol20200311Reference - Clin Res Cardiol 2020 Mar 11 early online
  • Study Summary
    7% incidence of acute cardiac injury and 16.7% incidence of arrhythmias in hospitalized patients with COVID-19 pneumonia in China
    Details
    studySummary
    • Cohort Study based on retrospective cohort study
    • 138 adults aged 22-92 years (median age 56 years, 54% men) with confirmed COVID-19 pneumonia consecutively admitted to Zhongnan Hospital in Wuhan, China, from January 1, 2020 to January 28, 2020, were evaluated through February 3, 2020
    • 31% had preexisting hypertension and 14.5% had preexisting cardiovascular disease
    • incidence of cardiac complications
      • 7.2% acute cardiac injury (defined as cardiac biomarkers > 99th percentile upper reference limit or new abnormalities on electrocardiography or echocardiogram)
      • 16.7% arrhythmia
    • PubMed32031570JAMAJAMA20200207Reference - JAMA 2020 Feb 7 early online, commentary can be found in JAMA 2020 Feb 5 early online

Pathogenesis of myocardial injury

Clinical presentation of COVID-19 in patients with preexisting cardiovascular disease and in patients COVID-19-related myocardial injury

  • diagnostic and screening considerations
    • diagnosis of COVID-19 may be challenging in patients with atypical presentation or preexisting cardiovascular disease
      • patients may rarely initially present with cardiovascular symptoms such as palpitations and chest tightness instead of respiratory symptoms
      • typical presenting symptoms of COVID-19 such as fatigue, dyspnea, and cough are similar to clinical presentation of preexisting cardiovascular disease such as decompensated heart failure or arrhythmias
      • PubMed32270559Journal of cardiovascular electrophysiologyJ Cardiovasc Electrophysiol20200409Reference - J Cardiovasc Electrophysiol 2020 Apr 9 early online
    • Cardiovascular_Disorders Emergency_Medicine Hospital_Medicine Internal_MedicineFDA issues Emergency Use Authorization permitting use of Eko electrocardiogram Low Ejection Fraction Tool (ELEFT) for assessment of left ventricular ejection fraction as diagnostic aid to screen adults for potential cardiac complications of COVID-19 or for underlying cardiac conditions that may affect management of COVID-19 (FDA Emergency Use Authorization 2020 May 11)05/14/2020 04:15:41 PMFDA issues Emergency Use Authorization permitting use of Eko electrocardiogram Low Ejection Fraction Tool (ELEFT) for assessment of left ventricular ejection fraction as diagnostic aid to screen adults for potential cardiac complications of COVID-19 or for underlying cardiac conditions that may affect management of COVID-19
      • ELEFT software device utilizes a machine learning algorithm via cloud-based software to identify left ventricular ejection fraction (LVEF) ≤ 40% via analysis of 10 seconds of a 12-lead electrocardiogram on a smartphone, tablet, or personal computer
      • ELEFT is intended for use when echocardiography is not available or indicated and is not intended as sole means for low LVEF diagnosis
      • ELEFT may be most helpful as a screening tool to determine whether further assessment by echocardiogram may be warranted
      • although early findings provided by ELEFT may help to inform care (particularly during patient intake and triage), diagnosis of cardiac conditions should be confirmed with physical exam and echocardiogram prior to treatment
      • References - FDA Emergency Use Authorization 2020 May 11, FDA Fact Sheet for Healthcare Providers 2020 May 11
  • Study Summary
    elevated d-dimer levels in 100%, and noncoronary myocardial injury in 56%, of 18 patients with COVID-19 and ST-segment elevation in New York City
    Details
    Cardiovascular_Disorders Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disorderselevated d-dimer levels in 100%, and noncoronary myocardial injury in 56%, of 18 patients with COVID-19 and ST-segment elevation in New York City (N Engl J Med 2020 Apr 17 early online)04/23/2020 03:34:00 PMstudySummary
    • Cohort Study based on cohort study
    • 18 adults (median age 63 years, 83% male) with confirmed COVID-19 and ST-segment elevation on ECG from 6 New York City hospitals were included
      • 10 patients (56%) had ST-segment elevation upon presentation, 8 patients (44%) developed ST-segment elevation during hospitalization after median of 6 days
      • patients assumed to have noncoronary myocardial injury if nonobstructive disease on coronary angiography or normal wall motion on echocardiography
    • underlying conditions included hypertension in 11 patients, hypercholesterolemia in 7 patients, diabetes in 6 patients, and history of coronary artery disease in 3 patients
    • all patients had elevated D-dimer levels
    • 10 patients (56%) had noncoronary myocardial injury, 8 patients (44%) had ST-segment elevation myocardial infarction (STEMI)
    • signs and symptoms included
      • elevated d-dimer levels in 100%
      • in patients with noncoronary myocardial injury: focal ST elevation in 60%, diffuse ST elevation in 40%, and low left ventricular ejection fraction in 20%
      • in patients with STEMI: focal ST elevation in 100% and low left ventricular ejection fraction in 88%
    • management included
      • in patients with noncoronary myocardial injury: hydroxychloroquine with azithromycin in 9 patients (90%), statins in 6 patients (60%), and glucocorticoids in 4 patients (40%)
      • in patients with STEMI: percutaneous coronary intervention (PCI) in 5 (63%), hydroxychloroquine with azithromycin in 5 (63%), and statins in 5 (63%)
    • in-hospital mortality 90% in patients with noncoronary myocardial injury and 50% in patients with STEMI
    • PubMed32302081The New England journal of medicineN Engl J Med20200417Reference - N Engl J Med 2020 Apr 17 early online
  • Study Summary
    cardiac troponin I, D-dimer, lymphocyte, interleukin-6, ferritin, and lactate dehydrogenase levels may increase over time in patients who do not survive COVID-19 infection but not in patients who survive infection
    Details
    Cardiovascular_Disorders Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disorderscardiac troponin I, D-dimer, lymphocyte, interleukin-6, ferritin, and lactate dehydrogenase levels may increase over time in patients who do not survive COVID-19 infection but not in patients who survive infection (Lancet 2020 Mar 11 early online)04/23/2020 03:31:50 PMstudySummary
    • Cohort Study based on retrospective cohort study
    • 191 adults aged 18-87 years (median age 56 years, 62% men) with laboratory-confirmed COVID-19 admitted to 2 hospitals in Wuhan, China, and who died (28%) or were discharged by January 31, 2020, were included
      • most common symptoms on admission included fever (94%), cough (79%), sputum (23%), fatigue (23%), and myalgia (15%)
      • 48% had comorbidities
    • 95% received antibiotics, and 21% received antivirals (lopinavir/ritonavir)
    • increased in-hospital mortality associated with
      • older age (adjusted odds ratio [OR] 1.1 per year increase, 95% CI 1.03-1.17)
      • higher SOFA score (adjusted OR 5.65, 95% CI 2.61-12.23)
      • d-dimer > 1 mcg/mL on admission (adjusted OR 18.42, 95% CI 2.64-128.55) compared to ≤ 0.5 mcg/mL
    • temporal lab findings comparing nonsurvivors vs. survivors
      Table 1. Median Lab Findings Comparing Nonsurvivors vs. Survivors by Day of Onset from Illness
      Day from Illness OnsetMedian High-Sensitivity Cardiac Troponin I (picograms/mL)Median D-Dimer Levels (mcg/mL)Median Lymphocyte Count (× 109/L)Median Interleukin-6 Levels (pg/mL)Median Ferritin (mcg/L)Median Lactate Dehydrogenase (Units/L)
      48.8 for nonsurvivors vs. 2.5 for survivors (not significant)0.3 for nonsurvivors vs. 0.3 for survivors (not significant)1.08 for nonsurvivors vs. 0.6 for survivors (p < 0.05) 9.5 for nonsurvivors vs. 5.5 for survivors (not significant)1,025 for nonsurvivors vs. 393 for survivors (p < 0.05)332 for nonsurvivors vs. 236 for survivors (p < 0.05)
      724.7 for nonsurvivors vs. 3.3 for survivors (p < 0.05)2.6 for nonsurvivors vs. 0.5 for survivors (p < 0.05)0.91 for nonsurvivors vs. 0.67 for survivors (p < 0.05)12 for nonsurvivors vs. 6.8 for survivors (p < 0.05)1,646 for nonsurvivors vs. 531 for survivors (p < 0.05)390 for nonsurvivors vs. 302 for survivors (p < 0.05)
      1022 for nonsurvivors vs. 4.1 for survivors (p < 0.05)14.4 for nonsurvivors vs. 0.6 for survivors (p < 0.05)0.97 for nonsurvivors vs. 0.52 for survivors (p < 0.05)10.7 for nonsurvivors vs. 6.6 for survivors (p < 0.05)1,645 for nonsurvivors vs. 546 for survivors (p < 0.05)397 for nonsurvivors vs. 301 for survivors (p < 0.05)
      1355.7 for nonsurvivors vs. 4.4 for survivors (p < 0.05)16.7 for nonsurvivors vs. 0.6 for survivors (p < 0.05)1.18 for nonsurvivors vs. 0.54 for survivors (p < 0.05)11.7 for nonsurvivors vs. 6.1 for survivors (p < 0.05)1,698 for nonsurvivors vs. 546 for survivors (p < 0.05)388 for nonsurvivors vs. 240 for survivors ( p < 0.05)
      1657.6 for nonsurvivors vs. 2.5 for survivors (p < 0.05)23.8 for nonsurvivors vs. 0.7 for survivors (p < 0.05)1.2 for nonsurvivors vs. 0.49 for survivors (p < 0.05)17.2 for nonsurvivors vs. 6.3 for survivors (p < 0.05)2,000 for nonsurvivors vs. 447 for survivors (p < 0.05)413 for nonsurvivors vs. 217 for survivors (p < 0.05)
      19134.5 for nonsurvivors vs. 2.5 for survivors (p < 0.05)35.6 for nonsurvivors vs. 1 for survivors (p < 0.05)1.41 for nonsurvivors vs. 0.54 for survivors (p < 0.05)26.4 for nonsurvivors vs. 7 for survivors (p < 0.05)> 2,000 for nonsurvivors vs. 432 for nonsurvivors (p < 0.05)528 for nonsurvivors vs. 198 for survivors (p < 0.05)
      22290.6 for nonsurvivors vs. 3.8 for survivors (p < 0.05)42.4 for nonsurvivors vs. 0.5 for survivors (p < 0.05)1.42 for nonsurvivors vs. 0.42 for survivors (p < 0.05)N/AN/A590 for nonsurvivors vs. 200 for survivors (p < 0.05)
      25N/AN/A1.43 for nonsurvivors vs. 0.44 for survivors (p < 0.05)N/AN/AN/A
      Abbreviation: N/A, not applicable.
    • PubMed32171076Lancet (London, England)Lancet20200311Reference - Lancet 2020 Mar 11 early online

Clinical presentation of COVID-19-related myocarditis

  • Study Summary
    dyspnea with or without chest pain, elevated cardiac biomarkers, electrocardiography abnormalities, and reduced cardiac function may be common in hospitalized patients with COVID-19-related myocarditis
    Details
    studySummary
    • Case ReportCase ReportCase ReportCase ReportCase Report based on 5 case reports
    • 69-year old man hospitalized with COVID-19 developed myocarditis
      • symptoms upon hospitalization included worsening dyspnea, persistent cough, and weakness for 4 days
      • elevated cardiac biomarkers included
        • C-reactive protein 52.7 mg/L
        • high-sensitivity troponin I 4,332 ng/L
      • imaging findings included
        • dilated left ventricle, severe and diffuse left ventricular hypokinesia, and reduced left ventricular ejection fraction on echocardiography
        • unremarkable findings on coronary angiography
      • left ventricular ejection fraction and severe hypotension developed 3 hours after hospitalization
      • endomyocardial biopsy findings included
        • low-grade interstitial and endocardial inflammation
        • large (> 20 mcm), vacuolated, CD68-positive macrophages on immune-light microscopy
        • viral particles with dense round viral envelope and electron-dense-spike-like structures on surface consistent with coronavirus size (70-120 nm) in cytopathic, structurally damaged interstitial cells with membrane damage on ultrastructural study
      • PubMed32275347European journal of heart failureEur J Heart Fail20200410Reference - Eur J Heart Fail 2020 Apr 10 early online
    • 63-year old man hospitalized with COVID-19 developed fulminant myocarditis
      • signs and symptoms upon hospitalization included chest tightness, dyspnea, fever, and sputum
      • elevated cardiac biomarkers included
        • troponin I 11.37 g/L
        • N-terminal brain natriuretic peptide (NT-BNP) 22,600 pg/mL
        • myoglobin 390.97 ng/mL
      • sinus tachycardia on electrocardiography
      • enlarged left ventricular, diffuse myocardial dyskinesia, reduced left ventricular ejection fraction, pulmonary hypertension, and reduced right cardiac function on bedside echocardiography
      • PubMed32277408InfectionInfection20200410Reference - Infection 2020 Apr 10 early online
    • 53-year old woman hospitalized with COVID-19 developed myopericarditis
      • signs and symptoms upon hospitalization included severe fatigue for 2 days after fever and cough in previous week
      • blood pressure 90/50 mm Hg
      • elevated cardiac biomarkers included
        • high-sensitivity troponin T 0.24 ng/mL
        • creatinine kinase-MB 20.3 ng/mL
        • NT-pro-BNP 5,647 pg/mL
        • C-reactive protein 1.3 mg/dL
      • low voltage in limb leads, minimal diffuse ST-segment elevation in inferior and lateral leads, and ST-segment depression with T-wave inversion in leads V1 and aVR on electrocardiography
      • imaging findings included
        • normal left ventricular dimensions with increased wall thickness, diffuse echo-bright myocardium, diffuse hypokinesis, mid-range left ventricular ejection fraction (40%), mildly impaired mitral inflow patterns, and pericardial effusion on transthoracic echocardiography
        • no coronary obstruction on coronary angiography
        • increased wall thickness with diffuse biventricular hypokinesis, reduced left ventricular ejection fraction (35%), and biventricular myocardial interstitial edema on cardiac magnetic resonance imaging
      • PubMed32219357JAMA cardiologyJAMA Cardiol20200327Reference - JAMA Cardiol 2020 Mar 27 early online
    • 37-year old man hospitalized with COVID-19 developed fulminant myocarditis and cardiogenic shock
      • symptoms included chest pain, dyspnea, and diarrhea for 3 days before hospitalization
      • blood pressure 80/55 mm Hg
      • elevated cardiac biomarkers included
        • troponin T > 10,000 ng/L
        • creatinine kinase isoenzyme 112.9 ng/L
        • brain natriuretic peptide (BNP) 21,025 ng/L
      • ST-segment elevation in leads III and aVF on electrocardiography
      • imaging findings included
        • enlarged heart (cardiothoracic ratio 0.7) on chest x-ray
        • pulmonary infection, enlarged heart, and pleural effusion on chest computed tomography
        • no coronary stenosis on emergency cardiac computed tomography angiography
        • enlarged heart, reduced left ventricular systolic function (left ventricle end-diastolic size 58 mm, left atrium size 39 mm, right ventricle size 25 mm, right atrium size 48 mm, left ventricular ejection fraction 27%), and pericardial effusion on echocardiography
      • PubMed32176300European heart journalEur Heart J20200316Reference - Eur Heart J 2020 Mar 16 early online
    • 21-year old woman hospitalized with COVID-19 developed myocarditis
      • signs and symptoms upon hospitalization included fever, coughing, sputum, diarrhea, and dyspnea
      • PubMed32282027European heart journalEur Heart J20200413elevated cardiac biomarkers included
        • troponin I 1.26 ng/L
        • N-terminal pro-brain natriuretic peptide (NT-proBNP) 1,929 pg/mL
      • nonspecific intraventricular conduction delay and multiple premature ventricular contractions on electrocardiography
      • imaging findings included
        • multifocal consolidation and ground-glass opacities on both lungs in lower lobe in peripheral dominant distribution on chest computed tomography
        • normal coronary arteries and hypertrophied myocardium due to edema with subendocardiac perfusion defect on lateral left ventricle on cardiac computed tomography
        • severe left ventricular systolic dysfunction on echocardiography
        • diffuse high signal intensity in left ventricular myocardium and myocardial wall thickening on cardiac magnetic resonance imaging
      • PubMed32282027European heart journalEur Heart J20200413Reference - Eur Heart J 2020 Apr 13 early online

Prognosis

Prognosis in patients with preexisting cardiovascular disease

  • Study Summary
    11% mortality in patients with cardiovascular disease (CVD) and confirmed COVID-19 in China
    Details
    studySummary
    • Cohort Study based on retrospective cohort study
    • 72,314 patients (age range < 10 to ≥ 80 years old) with suspected COVID-19 in China were evaluated through February 11, 2020
    • 62% had confirmed COVID-19 infection
    • mortality among patients with confirmed infection
      • 2.3% overall
      • 10.5% in patients with cardiovascular disease
      • 7.3% in patients with diabetes
      • 6.3% in patients with chronic respiratory disease
      • 6% in patients with hypertension
      • 5.6% in patients with cancer
    • PubMed32091533JAMAJAMA20200224Reference - JAMA 2020 Feb 24 early online
  • Evidence Synopsis


    Preexisting cardiovascular disease is associated with increased mortality in hospitalized patients with COVID-19, especially when patients present with elevated troponin T levels where the mortality may be three-fold higher (69.4% vs. 23%) compared to those without cardiovascular disease.
    • Study Summary
      cardiovascular disease associated with increased risk of in-hospital mortality in adults with COVID-19
      Details
      Cardiovascular_Disorderscardiovascular disease associated with increased risk of in-hospital mortality in adults with COVID-19 (N Engl J Med 2020 May 1 early online)05/07/2020 08:54:49 AMstudySummary
      • Cohort Study based on retrospective cohort
      • 8,910 adults (mean age 49 years, 16.5% > 65 years old) from Surgical Outcomes Collaborative with COVID-19 admitted to 169 hospitals in Asia, Europe, and North America (Surgical Outcomes Collaborative registry) between December 20, 2019 and March 15, 2020, were evaluated through March 28, 2020
        • coronary artery disease in 11.3%
        • cardiac arrhythmia in 3.4%
        • heart failure in 2.1%
        • chronic obstructive pulmonary disease in 2.5%
      • in-hospital mortality 5.8%
      • factors associated with increased risk of in-hospital mortality
        • coronary artery disease (odds ratio [OR] 2.7, 95% CI 2.08-3.51)
        • cardiac arrhythmia (OR 1.95, 95% CI 1.33-2.86)
        • heart failure (OR 2.48, 95% CI 1.62-3.79)
        • chronic obstructive pulmonary disease (OR 2.96, 95% CI 2-4.4)
        • age > 65 years old (OR 1.93, 95% CI 1.6-2.41)
      • PubMed32356626The New England journal of medicineN Engl J Med20200501Reference - N Engl J Med 2020 May 1 early online, editorial can be found in N Engl J Med 2020 May 1 early online
    • Study Summary
      preexisting CVD may be associated with increased mortality in patients hospitalized with COVID-19, especially when patients have elevated troponin T levels
      Details
      studySummary
      • Cohort Study based on retrospective cohort study
      • 187 patients (mean age 58 years) hospitalized with COVID-19 in Wuhan, China included
        • prevalence of preexisting CVD 35.3% overall
          • hypertension in 32.6%
          • coronary heart disease in 11.2%
          • cardiomyopathy in 4.3%
        • history of angiotensin-converting enzyme (ACE) inhibitor and/or angiotensin receptor blocker (ARB) use in 10.1%
      • mortality 23% overall
      • mortality based on presence of preexisting CVD and troponin T levels (no p values reported)
        • 69.4% in patients with preexisting CVD plus elevated troponin T
        • 37.5% in patients without preexisting CVD but with elevated troponin T
        • 13.3% in patients with preexisting CVD but without elevated troponin T
        • 7.6% in patients without preexisting CVD and without elevated troponin T
      • comparing patients with elevated troponin T vs. normal troponin T
        • mortality 59.6% vs. 8.9% (p < 0.001)
        • mechanical ventilation required in 59.6% vs. 10.4% (p < 0.001)
        • acute respiratory distress syndrome (ARDS) in 57.7% vs. 11.9% (p < 0.001)
        • ventricular tachycardia/fibrillation in 17.3% vs. 1.5% (p < 0.001)
        • acute coagulopathy in 65.8% vs. 20% (p < 0.001)
        • acute kidney injury in 36.8% vs. 4.7% (p < 0.001)
      • mortality 36.8% in patients with history of ACE inhibitor and/or ARB use vs. 25.6% in patients without history of ACE inhibitor and/or ARB use (no p value reported)
      • Reference - JAMA Cardiol 2020 Mar 27 early onlinefull-text
    • Study Summary
      older age and preexisting CVD associated with increased mortality in patients hospitalized with COVID-19
      Details
      Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disordersolder age and preexisting cardiovascular disease associated with increased mortality in patients hospitalized with COVID-19 (Intensive Care Med 2020 Mar 3 early online)03/05/2020 01:34:23 PMstudySummary
      • Cohort Study based on retrospective cohort study
      • 150 patients with COVID-19 at 2 hospitals in Wuhan, China, were evaluated
      • 68 patients died, with cause of death
        • respiratory failure in 53%
        • respiratory failure plus circulatory failure in 33%
        • circulatory failure in 7%
        • unknown cause in 7%
      • comparing patients who died vs. patients discharged
        • median age 67 years vs. 50 years (p < 0.001)
        • preexisting CVD in 19% vs. 0% (p < 0.001)
        • clinical factors
          • dyspnea in 87% vs. 62% (p = 0.001)
          • respiratory failure in 85% vs. 16% (p < 0.001)
          • ARDS in 81% vs. 9% (p < 0.001)
          • acute kidney injury in 31% vs. 2% (p < 0.001)
          • secondary infection in 16% vs. 1% (p = 0.002)
        • laboratory findings
          • mean white blood cell count 10.6 × 109 cells/L vs. 6.8 × 109 cells/L (p < 0.001)
          • mean lymphocyte count 0.6 × 109 cells/L vs. 1.4 × 109 cells/L (p < 0.001)
          • mean platelet count 174 × 109 cells/L vs. 222 × 109 cells/L (p < 0.001)
          • mean albumin 28.8 g/L vs. 32.7 g/L (p < 0.001)
          • mean blood urea nitrogen 8.7 mmol/L vs. 5.1 mmol/L (p < 0.001)
          • mean cardiac troponin 30.3 pg/mL vs. 3.5 pg/mL (p < 0.001)
          • mean C-reactive protein 126.6 mg/L vs. 34.1 mg/L (p < 0.001)
          • mean interleukin-6 11.4 ng/mL vs. 6.8 ng/mL (p < 0.001)
          • mean total bilirubin 18.1 mcmol/L vs. 12.8 mcmol/L (p = 0.001)
          • mean creatinine 91.2 mmol/L vs. 72.1 mmol/L (p = 0.02)
      • PubMed32125452Intensive care medicineIntensive Care Med20200303Reference - Intensive Care Med 2020 Mar 3 early online
    • Study Summary
      preexisting cardiac disease associated with increased mortality and complications in patients hospitalized with COVID-19 pneumonia
      Details
      Cardiovascular_Disorderspreexisting cardiac disease associated with increased mortality and complications in patients hospitalized with COVID-19 pneumonia (Eur Heart J 2020 May 14)05/26/2020 10:47:04 AMstudySummary
      • Cohort Study based on cohort study
      • 99 patients (mean age 67 years, 81% men) with COVID-19 pneumonia admitted to single hospital in northern Italy between March 4 and March 25, 2020, were assessed
      • 53 patients had history of cardiac disease (heart failure, atrial fibrillation, or coronary artery disease); 15 of these patients also had chronic kidney disease
      • 77% discontinued antihypertensive agents (including 2 patients without history of cardiac disease) due to severe hypotension
      • comparing cardiac disease vs. no cardiac disease
        • in-hospital mortality 36% vs. 15% (p = 0.02)
        • intensive care unit admission in 19% vs. 0% (p < 0.001)
        • septic shock in 11% vs. 0% (p = 0.019)
        • venous thromboembolism in 17% vs. 6% (p = 0.11)
        • arterial thromboembolism in 6% vs. 0% (p = 0.1)
        • ARDS in 23% vs. 15% (not significant)
      • PubMed32383763European heart journalEur Heart J2020051441191821-18291821Reference - Eur Heart J 2020 May 14;41(19):1821
  • use of ACE inhibitors or angiotensin II receptor blockers (ARBs)
    • Study Summary
      in-hospital use of ACE inhibitors or ARBs associated with reduced mortality in adults with hypertension hospitalized with COVID-19
      Details
      Cardiovascular_Disorders Hospital_Medicine Internal_Medicinein-hospital use of ACE inhibitors or ARBs associated with reduced mortality in adults with hypertension hospitalized with COVID-19 (Circ Res 2020 Apr 17 early online)05/07/2020 08:56:03 AMstudySummary
      • Cohort Study based on retrospective cohort study
      • 1,128 adults ≤ 74 years old (median age 64 years) with hypertension and confirmed COVID-19 admitted to hospitals in Hubei Province, China, from December 31, 2019 to February 20, 2020, were followed
        • 188 patients (16.7%) were taking ACE inhibitors or ARBs during hospitalization (ARBs in 83.5% of this group)
          • 9 patients discontinued ACE inhibitor/ARB use during hospitalization
          • some patients were placed on ACE inhibitor/ARB upon admission (proportion not reported)
        • 83.3% did not receive ACE inhibitors or ARBs
      • all patients had systolic blood pressure ≥ 140 mm Hg (median 132 mm Hg) or diastolic blood pressure ≥ 90 mm Hg (median 80 mm Hg)
      • other antihypertensive treatments included calcium channel blockers, beta-blockers and alpha-blockers
      • at presentation, prevalence of fever, dyspnea, and bilateral lung lesions was lower in ACE inhibitor/ARB group
      • comparing use of ACE inhibitors or ARBs vs. no use
        • 28-day all-cause mortality 3.7% vs. 9.8% (adjusted hazard ratio [HR] for death 0.42, 95% CI 0.19-0.92)
        • septic shock in 3.2% vs. 8% (adjusted HR 0.36, 95% CI 0.16-0.84)
      • use of ACE inhibitors or ARBs associated with reduced risk of ARDS (adjusted HR 0.69, 95% CI 0.47-1.02)
      • consistent results in propensity score-matched analysis (adjusted HR for death 0.37, 95% CI 0.15-0.89)
      • in propensity score-matched subgroup analysis, use of ACE inhibitors or ARBs associated with reduced mortality vs. other antihypertensive treatments (adjusted HR 0.3, 95% CI 0.12-0.7)
      • PubMed32302265Circulation researchCirc Res20200417Reference - Circ Res 2020 Apr 17 early online
    • Study Summary
      use of ACE inhibitors may reduce in-hospital mortality and use of ARBs may not increase in-hospital mortality in patients with COVID-19
      Details
      Cardiovascular_Disorders Hospital_Medicine Internal_Medicineuse of ACE inhibitors may reduce in-hospital mortality and use of ARBs may not increase in-hospital mortality in patients with COVID-19 (N Engl J Med 2020 May 1 early online)05/07/2020 08:57:07 AMstudySummary
      • Cohort Study based on retrospective cohort
      • 8,910 adults (mean age 49 years, 16.5% > 65 years old) from Surgical Outcomes Collaborative with COVID-19 admitted to 169 hospitals in Asia, Europe, and North America (Surgical Outcomes Collaborative registry) between December 20, 2019 and March 15, 2020, were evaluated through March 28, 2020
        • at baseline, 8.6% were taking ACE inhibitors and 6.2% were taking ARBs (in-hospital use not reported)
        • 26.3% had hypertension
      • mean duration of hospitalization 10.7 days
      • in-hospital mortality
        • 5.8% overall
        • 2.1% with use of ACE inhibitors vs. 6.1% with no use (adjusted odds ratio 0.33, 95% CI 0.2-0.54)
        • 6.8% with use of ARBs vs. 5.7% with no use (adjusted odds ratio 1.23, 95% CI 0.87-1.74)
      • PubMed32356626The New England journal of medicineN Engl J Med20200501Reference - N Engl J Med 2020 May 1 early online, editorial can be found in N Engl J Med 2020 May 1 early online
    • Study Summary
      use of ACE inhibitors/ARBs associated with lower rates of critical disease and improved infection-related biomarkers than other antihypertensives in patients with preexisting hypertension and COVID-19
      Details
      Cardiovascular_Disordersuse of ACE inhibitors/ARBs associated with lower rates of critical disease and improved infection-related biomarkers than other antihypertensives in patients with preexisting hypertension and COVID-19 (Hypertension 2020 Apr 29 early online)05/26/2020 10:48:50 AMstudySummary
      • Cohort Study based on retrospective cohort study
      • 126 adults (mean age 66 years) with preexisting hypertension who were hospitalized with COVID-19 in 1 hospital in Wuhan, China, from January 5 to February 22, 2020, were evaluated
      • 34% were using ACE inhibitors or ARBs; other patients used other antihypertensive agents
      • comparing use of ACE inhibitors/ARBs to other antihypertensives
        • critical disease in 9.3% vs 22.9% (p = 0.061)
        • mortality 4.7% vs 13.3% (not significant)
        • mean procalcitonin concentration 0.061 ng/mL vs. 0.121 ng/mL (p = 0.008)
        • mean hypersensitive C-reactive protein concentration 11.5 mg/L vs. 33.9 mg/L (p = 0.049)
      • no significant differences in blood pressure between groups
      • PubMed32348166Hypertension (Dallas, Tex. : 1979)Hypertension20200429Reference - Hypertension 2020 Apr 29 early online
  • Study Summary
    older age, higher Sequential Organ Failure Assessment (SOFA) score, and d-dimer > 1 mcg/mL associated with increased in-hospital mortality in adults with COVID-19
    Details
    Critical_Care Infectious_Diseases Internal_Medicine Pulmonary_Disordersolder age, higher Sequential Organ Failure Assessment score, and d-dimer > 1 mcg/mL associated with increased in-hospital mortality in adults with COVID-19 (Lancet 2020 Mar 11 early online)03/18/2020 01:22:56 PMstudySummary
    • Cohort Study based on retrospective cohort study
    • 191 adults aged 18-87 years (median age 56 years, 62% men) with laboratory-confirmed COVID-19 admitted to 2 hospitals in Wuhan, China, and who died (28%) or were discharged by January 31, 2020, were assessed
      • most common symptoms on admission included fever (94%), cough (79%), sputum (23%), fatigue (23%), and myalgia (15%)
      • 48% had comorbidity
    • 95% received antibiotics, and 21% received antivirals (lopinavir/ritonavir)
    • increased in-hospital mortality associated with
      • older age (adjusted odds ratio [OR] 1.1 per year increase, 95% CI 1.03-1.17)
      • higher SOFA score (adjusted OR 5.65, 95% CI 2.61-12.23)
      • d-dimer > 1 mcg/mL on admission (adjusted OR 18.42, 95% CI 2.64-128.55) compared to ≤ 0.5 mcg/mL
    • comparing nonsurvivors vs. survivors (p < 0.0001 for each unless otherwise indicated)
      • median age 69 years vs. 52 years
      • SOFA score 4.5 points vs. 1 point
      • comorbidities
        • hypertension in 48% vs. 23% (p = 0.0008)
        • diabetes in 31% vs. 14% (p = 0.0051)
        • coronary heart disease in 24% vs. 1%
        • chronic obstructive lung disease in 7% vs. 1% (p = 0.047)
        • chronic kidney disease in 4% vs. 0% (p = 0.024)
      • laboratory findings
        • d-dimer ≥ 1 mcg/mL in 81% vs. 24%
        • median white blood cell count 9.8 × 109/L vs. 5.2 × 109/L
        • lymphocyte < 0.8 × 109/L in 76% vs. 26%
        • anemia in 26% vs. 11% (p = 0.0094)
        • platelet count < 100 × 109/L in 20% vs. 1%
        • high-sensitivity cardiac troponin I ≥ 28 pg/mL in 46% vs. 1%
      • thoracic imaging
        • consolidation in 74% vs. 53% (p = 0.0065)
        • ground glass opacity in 81% vs. 67% (p = 0.049)
        • bilateral pulmonary infiltration in 83% vs. 72% (p = 0.09)
      • outcomes
        • sepsis in 100% vs. 42%
        • respiratory failure in 98% vs. 36%
        • ARDS in 93% vs. 7%
        • septic shock in 70% vs. 0%
        • acute cardiac injury in 59% vs. 1%
        • acute kidney injury in 50% vs. 1%
        • heart failure in 52% vs. 12%
        • secondary infection in 50% vs. 1%
        • coagulopathy in 50% vs. 7%
      • treatments
        • invasive mechanical ventilation in 57% vs. 1%
        • noninvasive mechanical ventilation in 44% vs. 1%
        • extracorporeal membrane oxygenation in 6% vs. 0% (p = 0.0054)
        • renal replacement therapy in 19% vs. 0%
        • IV immunoglobulin in 67% vs. 7%
        • corticosteroid in 48% vs. 23% (p = 0.0005)
    • median time from illness onset to
      • discharge 22 days
      • death 18.5 days
      • invasive mechanical ventilation 14.5 days
      • stop viral shedding in survivors 20 days (range 8-37 days)
    • PubMed32171076Lancet (London, England)Lancet20200311Reference - Lancet 2020 Mar 28;395(10229):1054
  • risk factors for increased mortality in patients in Italy compared to patients in China in retrospective cohort study
    • underlying conditions
      • cancer (odds ratio [OR] 11.73, 95% CI 5.14-26.77)
      • hypertension (OR 3.46, 95% CI 2.68-4.46)
      • chronic respiratory disease (OR 2.3, 95% CI 1.54-3.44)
      • cardiovascular disease (OR 1.91, 95% CI 1.45-2.5)
      • diabetes (OR 1.82, 95% CI 1.22-2.15)
    • demographic factors
      • age > 60 years (OR 4.63, 95% CI 3.87-5.55)
      • male sex (OR 1.27, 95% CI 1.11-1.46)
    • PubMed32275075Journal of medical virologyJ Med Virol20200410Reference - J Med Virol 2020 Apr 10 early online

Prognosis with COVID-19-related elevated cardiac troponin levels in patients with or without preexisting cardiovascular disease

  • Study Summary
    acute myocardial injury may be more common in patients with preexisting cardiovascular disease and may be associated with increased morbidity and mortality in patients hospitalized with COVID-19
    Details
    studySummary
    • Cohort StudyCohort Study based on 2 retrospective cohort studies
    • 416 patients aged 21-95 years hospitalized with confirmed COVID-19 in Wuhan, China from January 20, 2020 to February 10, 2020 included
      • most common preexisting conditions included hypertension in 30.5%, diabetes in 14.4%, coronary artery disease in 10.6%, and cerebrovascular disease in 5.3%
      • prevalence of cardiac injury (defined as high-sensitivity troponin I > 99th percentile upper reference limit)
        • 19.7% overall
        • 59.8% in patients with hypertension (p < 0.001 compared to patients without hypertension)
        • 24.4% in patients with diabetes (p = 0.008 compared to patients without diabetes)
        • 29.3% in patients with coronary artery disease (p < 0.001 compared to patients without coronary artery disease)
        • 15.9% in patients with cerebrovascular disease (p < 0.001 compared to patients without cerebrovascular disease)
      • outcomes comparing patients with acute cardiac injury vs. without acute cardiac injury
        • mortality 51.2% vs. 4.5% (p < 0.001)
        • acute respiratory distress syndrome in 58.5% vs. 14.7% (p < 0.001)
        • invasive mechanical ventilation used in 22% vs. 4.2% (p < 0.001)
        • acute kidney injury in 8.5% vs. 0.3% (p < 0.001)
        • electrolyte disturbance in 15.9% vs. 5.1% (p = 0.003)
        • hypoproteinemia in 13.4% vs. 4.8% (p = 0.01)
        • coagulation disorders in 7.3% vs. 1.8% (p = 0.02)
        • noninvasive ventilation used in 46.3% vs. 3.9% (p < 0.001)
        • glucocorticoid used in 87.8% vs. 69.5% (p < 0.001)
      • PubMed32211816JAMA cardiologyJAMA Cardiol20200325Reference - JAMA Cardiol 2020 Mar 25 early online
    • 187 patients (mean age 58 years,) hospitalized with COVID-19 in Wuhan, China from January 23, 2020, to February 23, 2020 included
      • 35.3% prevalence of preexisting cardiovascular disease, including hypertension, coronary heart disease, and cardiomyopathy
      • acute myocardial injury (defined as elevated cardiac troponin T) in
        • 27.8% overall
        • 54.5% in patients with preexisting cardiovascular disease
        • 13.2% in patients without cardiovascular disease
      • 23% died and 77% were discharged
      • mortality by presence of preexisting cardiovascular disease and acute myocardial injury
        • 7.6% in patients without cardiovascular disease and no acute myocardial injury
        • 13.3% in patients with cardiovascular disease but no acute myocardial injury
        • 37.5% in patients without cardiovascular disease but with acute myocardial injury
        • 69.4% in patients with cardiovascular disease and with acute myocardial injury
      • outcomes comparing patients with acute myocardial injury vs. no acute myocardial injury
        • mortality 59.6% vs. 8.9% (p < 0.001)
        • ventricular tachycardia/fibrillation in 17.3% vs. 1.5% (p < 0.001)
        • acute respiratory distress syndrome in 57.7% vs. 11.9% (p < 0.001)
        • acute coagulopathy in 65.8% vs. 20% (p < 0.001)
        • kidney injury in 36.8% vs. 4.7% (p < 0.001)
        • mechanical ventilation used in 59.6% vs. 10.4% (p < 0.001)
        • glucocorticoid therapy used in 71.2% vs. 51.1% (p = 0.01)
      • PubMed32219356JAMA cardiologyJAMA Cardiol20200327Reference - JAMA Cardiol 2020 Mar 27 early onlinefull-text
  • Study Summary
    myocardial injury, CD3+CD8+ T cells, and age ≥ 65 years associated with increased mortality in hospitalized patients with confirmed COVID-19 pneumonia
    Details
    Cardiovascular_Disorders Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disordersmyocardial injury, CD3+CD8+ T cells, and age ≥ 65 years associated with increased mortality in hospitalized patients with confirmed COVID-19 pneumonia (Eur Respir J 2020 Apr 8 early online)04/23/2020 03:37:22 PMstudySummary
    • Cohort Study based on prospective cohort study
    • 179 patients (mean age 57 years, 54% male) with confirmed COVID-19 pneumonia hospitalized in Wuhan, China from December 25, 2019 to February 7, 2020 included
    • most common preexisting comorbidities included hypertension in 32.4%, diabetes in 18.4%, cardiovascular or cerebrovascular disease in 16.2%, and chronic digestive disorders in 11.7%
    • 11.7% mortality
    • factors associated with increased mortality included
      • cardiac troponin I ≥ 0.05 ng/mL (myocardial injury) (adjusted odds ratio [OR] 4.08, 95% CI 1.17-14.25)
      • CD3+CD8+ T cells ≤ 75 cells/mcL (adjusted OR 3.98, 95% CI 1.13-14)
      • age ≥ 65 years (adjusted OR 3.77, 95% CI 1.15-17.39)
    • PubMed32269088The European respiratory journalEur Respir J20200408Reference - Eur Respir J 2020 Apr 8 early onlinefull-text
  • Study Summary
    acute cardiac injury, cardiocerebrovascular disease, and hypertension associated with increased risk of intensive care unit (ICU) admission in patients hospitalized with COVID-19
    Details
    studySummary
    • Systematic Review based on systematic review
    • systematic review of 6 studies evaluating prevalence of cardiovascular metabolic disease in 1,527 hospitalized patients with COVID-19 in China
    • median age 34-57 years across studies and 58% male
    • prevalence of cardiovascular metabolic disease
      • preexisting hypertension 17.1% (95% CI 9.9%-24%) in analysis of 4 studies with 1,415 patients
      • preexisting cardiocerebrovascular disease 16.4% (95% CI 6.6%-26.1%) in analysis of 5 studies with 1,514 patients
      • preexisting diabetes 9.7% (95% CI 6.9%-12.5%) in analysis of 5 studies with 1,514 patients
      • acute cardiac injury on lab results
        • 8% (95% CI 4.1%-12%) in analysis of 2 studies with 179 patients and cardiac injury defined as elevated cardiac troponin I/T
        • 11.5% (95% CI 7.8%-15.2%) in analysis of 2 studies with 1,198 patients and cardiac injury defined as elevated creatinine kinase
    • prevalence of cardiovascular metabolic disease and cardiac injury comparing patients admitted to ICU vs. patients not admitted to ICU
      • acute cardiac injury (defined as elevated troponin I/T) 24.5% vs. 2.3% (risk ratio [RR] 13.48, 95% CI 3.6-50.47) in analysis of 2 studies with 179 patients
      • cardiocerebrovascular disease 16.7% vs. 6.2% (RR 3.3, 95% CI 2.03-5.36) in analysis of 3 studies with 1,278 patients
      • hypertension 28.8% vs. 14.1% (RR 2.03, 95% CI 1.54-2.68) in analysis of 3 studies with 1,278 patients
      • diabetes 11.7% vs. 4% (RR 2.21, 95% CI 0.88-5.57) in analysis of 3 studies with 1,278 patients, not significant but CI includes differences that may be clinically important and results limited by significant heterogeneity
    • PubMed32161990Clinical research in cardiology : official journal of the German Cardiac SocietyClin Res Cardiol20200311Reference - Clin Res Cardiol 2020 Mar 11 early online

Prognosis in patients with COVID-19 related myocarditis

  • high morbidity and mortality reported in patients with COVID-19-related myocarditis in case reports
    • 37-year-old man with fulminant myocarditis remained hospitalized but recovered from symptoms, elevated cardiac biomarkers, enlarged heart, and systolic function after 3 weeks and treatment with methylprednisone 200 mg/day for 4 days, immunoglobulin 20 g/day for 4 days, norepinephrine, diuretic, milrinone, piperacillin sulbactam, and pantoprazole in case report (Eur Heart J 2020 Mar 16 early online)
    • 63-year-old man with fulminant myocarditis and co-infection with Candida, human alpha-herpesvirus, and beta-herpesvirus died despite gradual recovery of elevated cardiac biomarkers and left ventricular ejection fraction after treatment with ventilation, high-flow oxygen, lopinavir-ritonavir antiviral therapy, interferon alpha-1b, methylprednisolone, immunoglobulin, piperacillin–tazobactam, continuous renal replacement therapy, and extracorporeal membrane oxygenation (ECMO) in case report (Infection 2020 Apr 10 early online)
    • 69-year-old man with myocarditis and gram-negative pneumonia co-infection died 12 days after weaning from ECMO despite progressive recovery of left ventricular function after ECMO and intra-aortic balloon pump in case report (Eur J Heart Fail 2020 Apr 10 early online)
    • PubMed32253449Intensive care medicineIntensive Care Med20200406fulminant myocarditis as cause of death in 5 of 68 patients who died in retrospective cohort study of 150 patients hospitalized with COVID-19 in China (Intensive Care Med 2020 Mar 3 early onlinefull-text)

Guidelines and Resources

Guidelines and Resources

Guidelines

International Guidelines

United States Guidelines

  • PubMed32330544Journal of the American College of CardiologyJ Am Coll Cardiol20200421Society for Cardiovascular Angiography and Interventions/American College of Cardiology/American College of Emergency Physicians (SCAI/ACC/ACEP) consensus statement on management of acute myocardial infarction during the COVID-19 pandemic can be found in J Am Coll Cardiol 2020 Apr 21 early onlinefull-text
  • PubMed32247013Heart rhythmHeart Rhythm20200401Heart Rhythm Society/American College of Cardiology/American Heart Association (HRS/ACC/AHA) guidance on cardiac electrophysiology during coronavirus (COVID-19) can be found in Heart Rhythm 2020 Apr 1 early onlinefull-text and in Circulation 2020 May 26;141(21):e823
  • PubMed32267732CirculationCirculation20200408American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) joint statement on considerations for drug interactions on QTc in exploratory COVID-19 treatment can be found in Circulation 2020 Apr 8 early online
  • American Heart Association (AHA) interim guidance on healthcare providers during COVID-19 outbreak: CPR and emergency cardiovascular care can be found at AHA 2020 Mar PDF
  • PubMed32317235Journal of cardiovascular computed tomographyJ Cardiovasc Comput Tomogr20200101142101-104101Society of Cardiovascular Computed Tomography (SCCT) guidance on use of cardiac computed tomography (CT) during COVID-19 pandemic can be found in J Cardiovasc Comput Tomogr 2020 Mar;14(2):101full-text
  • Heart Failure Society of America/American Heart Association/American College of Cardiology (HFSA/AHA/ACC) joint statement on use of renin-angiotensin-aldosterone system (RAAS) antagonists can be found at ACC 2020 Mar 17
  • American College of Cardiology (ACC) clinical guidance on
  • American Heart Association/American Academy of Pediatrics/American Association for Respiratory Care/American College of Emergency Physicians/Society of Critical Care Anesthesiologists/American Society of Anesthesiologists (AHA/AAP/AARC/ACEP/SCCA/ASA) interim guidance on basic and advanced life support in adults, children, and neonates with suspected or confirmed COVID-19 can be found in Circulation 2020 Apr 9 early online
  • American College of Surgeons (ACS) guidance on triage of cardiac surgery patients can be found at ACS 2020 Mar 24 PDF
  • PubMed32199938Journal of the American College of CardiologyJ Am Coll Cardiol20200316American College of Cardiology/Society of Cardiovascular Angiography and Intervention (ACC/SCAI) guidance on catheterization laboratory considerations during COVID-19 pandemic can be found in J Am Coll Cardiol 2020 May 12;75(18):2372
  • American Society of Echocardiography (ASE) statement on protection of patients and echocardiography service providers during COVID-19 pandemic can be found at ASE 2020 Apr 1 PDF
  • American Society of Nuclear Cardiology/International Atomic Energy Agency/Society for Nuclear Medicine and Molecular Imaging (ASNC/IAEA/SNMMI) information statement on guidance and best practices for reestablishment of non-emergent care in nuclear cardiology laboratories during the coronavirus disease 2019 (COVID-19) pandemic can be found at Zenodo 2020 May 14
  • PubMed32415626Journal of nuclear cardiology : official publication of the American Society of Nuclear CardiologyJ Nucl Cardiol20200515 American Society of Nuclear Cardiology/Society for Nuclear Medicine and Molecular Imaging (ASNC/SNMMI) information statement on guidance and best practices for nuclear cardiology laboratories during COVID-19 pandemic can be found in J Nucl Cardiol 2020 May 15 early onlinefull-text

United Kingdom Guidelines

  • National Institute for Health and Care Excellence (NICE) COVID-19 rapid guideline on acute myocardial injury can be found at NICE 2020 Apr:NG171PDF
  • British Society of Echocardiography (BSE) guidance on echocardiography during COVID-10 pandemic can be found at BSE 2020 Apr 2

Canadian Guidelines

  • Canadian Cardiovascular Society (CCS) guidance on COVID-19 and concerns regarding use of cardiovascular medications, including ACEi/ARB/ARNi, low-dose ASA and non-steroidal anti-inflammatory drugs (NSAIDS) can be found at CCS 2020 Mar 20 PDF

European Guidelines

  • European Society of Cardiology (ESC) guidance on diagnosis and management of CV disease during the COVID-19 pandemic can be found at ESC 2020 Apr 21
  • PubMed32242891European heart journal cardiovascular ImagingEur Heart J Cardiovasc Imaging20200403European Association of Cardiovascular Imaging (EACVI) recommendations on cardiac imaging: precautions, indications, prioritization, and protection for patients and healthcare personnel can be found in Eur Heart J Cardiovasc Imaging 2020 Jun 1;21(6):592full-text
  • European Society of Cardiology (ESC) Council on Hypertension position statement on hypertension on ACE-inhibitors and angiotensin receptor blockers can be found at ESC 2020 Mar 13
  • Spanish Society of Cardiology (Sociedad Española de Cardiología [SEC]) Interventional Cardiology and Heart Rhythm Associations consensus document on invasive cardiac procedures during COVID-19 pandemic can be found at Rec Int Card 2020 Mar 20 early online
  • PubMed32223063Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & InterventionsCatheter Cardiovasc Interv20200329Italian Society of Interventional Cardiology (Società Italiana di Cardiologia Interventistica [GISE]) position paper on cath lab-specific preparedness for healthcare providers can be found in Catheter Cardiovasc Interv 2020 Mar 29 early onlinefull-text

Asian Guidelines

  • PubMed32278018Indian pacing and electrophysiology journalIndian Pacing Electrophysiol J20200408Indian Heart Rhythm Society scientific statement on cardiovascular risks of hydroxychloroquine for treatment and prophylaxis of COVID-19 can be found in Indian Pacing Electrophysiol J 2020 May;20(3):117full-text
  • PubMed32216640CirculationCirculation20200327Chinese Society of Cardiology (CSC) expert consensus on clinical management of patients with severe emergent cardiovascular disease during COVID-19 pandemic can be found in Circulation 2020 May 19;141(20):e810

Australian and New Zealand Guidelines

  • Cardiac Society of Australia and New Zealand/National Heart Foundation/High Blood Pressure Research Council of Australia/Australian and New Zealand Society of Cardiac and Thoracic Surgeons (CSANZ/NHF/HBPRCA/ANZSCTS) consensus statement on cardiovascular disease and COVID-19 can be found at MJA 2020 Apr 3
  • Cardiac Society of Australia and New Zealand (CSANZ)
    • CSANZ position statement on evaluation of patients presenting with suspected acute coronary syndromes during the COVID-19 pandemic can be found at CSANZ 2020 Apr 21 PDF
    • CSANZ position statement on optimising secondary prevention and cardiac rehabilitation for atherosclerotic cardiovascular disease during the COVID-19 pandemic can be found at CSANZ 2020 Apr 20 PDF
    • CSANZ consensus statement on rural and remote cardiology during the COVID-19 pandemic can be found at CSANZ 2020 Apr 11 PDF
    • CSANZ position statement on COVID-19 and acute heart failure can be found at CSANZ 2020 Apr 10 PDF
    • CSANZ position statement on management of cardiac electrophysiology and cardiac implantable electronic devices in Australia during the COVID-19 pandemic can be found at CSANZ 2020 Apr 9 PDF
    • CSANZ consensus statement on patients with genetic heart disease and COVID-19 can be found at CSANZ 2020 Apr 7 PDF
    • CSANZ position statement on echocardiography services during the COVID-19 pandemic can be found at CSANZ 2020 Mar 30 PDF
    • CSANZ consensus guideline on interventional cardiology services delivery during COVID-19 pandemic can be found at CSANZ 2020 Mar 29 PDF

Other Guidelines

Review Articles

Patient Information

References

Recommendation grading systems used

  • National Institutes of Health (NIH) recommendation rating scheme
    • strength of recommendation
      • A - strong recommendation for the statement
      • B - moderate recommendation for the statement
      • C - optional recommendation for the statement
    • quality of evidence for recommendation
      • I - ≥ 1 randomized trials with clinical outcomes and/or validated laboratory endpoints
      • II - ≥ 1 more well-designed, nonrandomized trials or observational cohort studies
      • III - expert opinion
    • Reference - NIH COVID-19 treatment guideline (NIH 2020 Apr 21)

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