Highlights
- •Virus-negative myocarditis(VNM) is an inflammatory disease with diverse etiologies.
- •A shared immune-mediated pathogenic process leads to inflammation and tissue damage.
- •Therapies effectively curbing myocardial inflammation can improve patient's outcome.
- •We reviewed current immune-modulatory opportunities to treat VNM.
- •Promising therapies could pave the way to future strategies for VNM.
Abstract
Virus-negative or autoimmune myocarditis(VNM) is an inflammatory disease affecting
the myocardium that may occur as a distinct disease with exclusive cardiac involvement,
or in the context of systemic autoimmune or inflammatory disorders. The pathogenesis
of VNM involves both innate and acquired immunity and is not completely elucidated:
an early immune-mediated pathogenic process lead to subacute and chronic stages and
eventually results in tissue remodeling, fibrosis, contractile dysfunction, dilated
cardiomyopathy and arrhythmic burden, accounting for a dismal prognosis. Treatment
interventions effectively curbing the acute inflammatory process at an early stage
can prevent late cardiac remodeling and improve patient's outcome. The mainstay of
treatment of VNM remains symptomatic therapy of heart failure and arrhythmia, while
the use of immunosuppressive treatments has long been considered controversial until
recently, and strategies effectively targeting the inflammatory and immune-mediated
substrate of the disease remain elusive. Only steroids and azathioprine have been
tested in clinical trials, and nowadays represent the therapy of choice. A substantial
proportion of patients are resistant to first line strategies, suggesting that some
critical inflammatory mechanisms are not responsive to conventional immunosuppression
with steroids and azathioprine, or experience drug-related adverse events. Thus, second-line
targeted therapeutic strategies to treat VNM are eagerly awaited.
Recent data on the pathogenic mechanisms underlying myocardial inflammation are paving
the way to novel, promising treatment strategies for myocarditis, which could reformulate
future treatment strategies for VNM.
In this review, we summarize the current therapeutic opportunities, beyond corticosteroids,
to treat VNM, including conventional and biologic immunosuppressive drugs and cytokine
blocking agents.
Keywords
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References
- Report of the 1995 World Health Organization/International Society and Federation of Cardiology task force on the definition and classification of cardiomyopathies.Circulation. 1996; 93 (Mar 1): 841-842https://doi.org/10.1161/01.CIR.93.5.841
- Dilated cardiomyopathy.Lancet. 2010; 375 (Feb 27): 752-762https://doi.org/10.1016/S0140-6736(09)62023-7
- Myocarditis. A histopathologic definition and classification.Am J Cardiovasc Pathol. 1987; 1 (Jan): 3-14
- Myocarditis: current trends in diagnosis and treatment.Circulation. 2006; 113 (Feb 14): 876-890https://doi.org/10.1161/CIRCULATIONAHA.105.584532
- Immune-mediated and autoimmune myocarditis: clinical presentation, diagnosis and management.Heart Fail Rev. 2013; 18 (Nov): 715-732https://doi.org/10.1007/s10741-012-9364-5
- Myocarditis: infection versus autoimmunity.J Clin Immunol. 2009; 29 (Nov): 730-737https://doi.org/10.1007/s10875-009-9339-z
- Myocarditis in auto-immune or auto-inflammatory diseases.Autoimmun Rev. 2017; 16 (Aug): 811-816https://doi.org/10.1016/j.autrev.2017.05.021
- Life-threatening arrhythmias in a scleroderma patient: the role of myocardial inflammation in arrhythmic outburst.Scand J Rheumatol. 2017; 46 (Jan): 78-80https://doi.org/10.3109/03009742.2016.1157626
- Unexpected acute lymphocytic virus-negative myocarditis in a patient with limited cutaneous systemic sclerosis: a case report.Scand J Rheumatol. 2019; 48 (Mar): 166-167https://doi.org/10.1080/03009742.2018.1493744
- Troponin in stable ischemic heart disease and diabetes.N Engl J Med. 2015; 373 (Nov 12): 1977-1978https://doi.org/10.1056/NEJMc1511645
- Recognizing and treating myocarditis in recent- onset systemic sclerosis heart disease: Potential utility of immunosuppressive therapy in cardiac damage progression.Semin Arthritis Rheum. 2014; 43 (Feb): 526-535https://doi.org/10.1016/j.semarthrit.2013.07.006
- Prognostic role of ventricular ectopic beats in systemic sclerosis: a prospective cohort study shows ECG indexes predicting the worse outcome.PLoS One. 2016; 11 (Apr 21)e0153012https://doi.org/10.1371/journal.pone.0153012
- Cardiac troponin T and NT-proBNP as diagnostic and prognostic biomarkers of primary cardiac involvement and disease severity in systemic sclerosis: a prospective study.Eur J Intern Med. 2019; 60 (Feb): 46-53https://doi.org/10.1016/j.ejim.2018.10.013
- QTc interval prolongation in Systemic Sclerosis: correlations with clinical variables and arrhythmic risk.Int J Cardiol. 2017; 239 (Jul 15): 33https://doi.org/10.1016/j.ijcard.2017.03.088
- Impact of systemic immune-mediated diseases on clinical features and prognosis of patients with biopsy-proved myocarditis.Int J Cardiol. 2019; 280 (Apr 1): 110-116https://doi.org/10.1016/j.ijcard.2018.11.104
- Successful use of sirolimus in a patient with cardiac microangiopathy in primary antiphospholipid syndrome.Scand J Rheumatol. 2019; (Feb 22): 1-2https://doi.org/10.1080/03009742.2019.1574022
- Efficacy and safety of mycophenolate mofetil in patients with virus-negative lymphocytic myocarditis: a prospective cohort study.J Autoimmun. 2020; 106 (Jan)102330https://doi.org/10.1016/j.jaut.2019.102330
- Anti-Ku syndrome with elevated CK: association with myocardial involvement in systemic sclerosis.Ann Rheum Dis. 2019; (annrheumdis-2019-216070)https://doi.org/10.1136/annrheumdis-2019-216070
- Systemic sclerosis myocarditis has unique clinical, histological and prognostic features: a comparative histological analysis.Rheumatology (Oxford). 2020; (kez658)https://doi.org/10.1093/rheumatology/kez658
- Myocarditis in patients treated with immune checkpoint inhibitors.J Am Coll Cardiol. 2018; 71: 1755-1764https://doi.org/10.1016/j.jacc.2018.02.037
- Letter by Campochiaro et al regarding article, "Clinical features, management, and outcomes of immune checkpoint inhibitor-related cardiotoxicity.Circulation. 2018; 137: 2421-2422https://doi.org/10.1161/CIRCULATIONAHA.117.033305
- Human parvovirus B19-associated myocarditis.N Engl J Med. 2010; 362 (Apr 1): 1248-1249https://doi.org/10.1056/NEJMc0911362
- Unresolved issues in theories of autoimmune disease using myocarditis as a framework.J Theor Biol. 2015; 375 (Jun 21): 101-123https://doi.org/10.1016/j.jtbi.2014.11.022
- European society of cardiology working group on myocardial and pericardial diseases. current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European society of cardiology working group on myocardial and pericardial diseases.Eur Heart J. 2013; 34 (Sep2648a-2648d): 2636-2648https://doi.org/10.1093/eurheartj/eht210
- Viral myocarditis – diagnosis, treatment options, and current controversies.Nat Rev Cardiol. 2015; 12 (Nov): 670-680https://doi.org/10.1038/nrcardio.2015.108
- Sudden adult death syndrome and other nonischaemic causes of sudden cardiac death.Heart. 2006; 92 (Mar): 316-320https://doi.org/10.1136/hrt.2004.045518
- Arrhythmias in myocarditis: state of the art.Heart Rhythm. 2019; 16 (May): 793-801https://doi.org/10.1016/j.hrthm.2018.11.024
- Ventricular arrhythmias in myocarditis: characterization and relationships with myocardial inflammation.J Am Coll Cardiol. 2020; 75: 1046-1057https://doi.org/10.1016/j.jacc.2020.01.036
- A clinical trial of immunosuppressive therapy for myocarditis. The myocarditis treatment trial investigators.N Engl J Med. 1995; 333 (Aug 3): 269-275https://doi.org/10.1056/NEJM199508033330501
- Necrotizing myocardial vasculitis in Churg-Strauss syndrome: clinicohistologic evaluation of steroids and immunosuppressive therapy.Chest. 1998; 114 (Nov): 1484-1489https://doi.org/10.1378/chest.114.5.1484
- Cardiac sarcoidosis.Am J Cardiol. 2019; 123 (Feb 1): 513-522https://doi.org/10.1016/j.amjcard.2018.10.021
- Idiopathic giant-cell myocarditis: natural history and treatment: multicenter giant cell myocardi- tis study group investigators.N Engl J Med. 1997; 336 (Jun 26): 1860-1866https://doi.org/10.1056/NEJM199706263362603
- Task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European society of cardiology (ESC). 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the european society of cardiology (ESC) endorsed by: association for european paediatric and congenital cardiology (AEPC).Europace. 2015; 17: 1601-1687https://doi.org/10.1093/europace/euv319
- ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European society of cardiology (ESC). Developed with the special contribution of the heart failure association (HFA) of the ESC.Eur J Heart Fail. 2016; 18 (2016 Aug): 891-975https://doi.org/10.1002/ejhf.592
- Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: the TIMIC study.Eur Heart J. 2009; 30 (Aug): 1995-2002https://doi.org/10.1093/eurheartj/ehp249
- Immunosuppressive therapy for active lymphocytic myocarditis: virological and immunologic profile of responders versus nonresponders.Circulation. 2003; 107 (Feb 18): 857-863
- Giant cell myocarditis treatment trial investigators. Usefulness of immunosuppression for giant cell myocarditis.Am J Cardiol. 2008; 102 (Dec 1): 1535-1539https://doi.org/10.1016/j.amjcard.2008.07.041
- Long-term outcome of patients with virus-negative chronic myocarditis or inflammatory cardiomyopathy after immunosuppressive therapy.Clin Res Cardiol. 2016; 105 (Dec): 1011-1020https://doi.org/10.1007/s00392-016-1011-z
- Myocarditis in patients with antisynthetase syndrome: prevalence, presentation, and outcomes.Medicine (Baltimore). 2015; 94 (Jul): e798https://doi.org/10.1097/MD.0000000000000798
- Lupus myocarditis receiving the rituximab therapy—a monocentric retrospective study.Clin Rheumatol. 2018; 37 (Jun): 1701-1707https://doi.org/10.1007/s10067-017-3971-4
- Lupus myocarditis: a single center experience and a comparative analysis of observational cohort studies.Lupus. 2018; 27 (Jul): 1296-1302https://doi.org/10.1177/0961203318770018
- Effects of methotrexate on plasma cytokines and cardiac remodeling and function in postmyocarditis rats.Mediators Inflamm. 2009; 2009389720https://doi.org/10.1155/2009/389720
- Understanding the mechanisms of action of methotrexate: implications for the treatment of rheumatoid arthritis.Bull NYU Hosp Jt Dis. 2007; 65: 168-173
- Pharmacological activation of AMPK prevents Drp1-mediated mitochondrial fission and alleviates endoplasmic reticulum stress-associated endothelial dysfunction.J Mol Cell Cardiol. 2015; 86 (Sep): 62-74https://doi.org/10.1016/j.yjmcc.2015.07.010
- Myocarditis in adult-onset still disease.Medicine (Baltimore). 2014; 93 (Oct): 280-289https://doi.org/10.1097/MD.0000000000000112
- Treatment of cardiac sarcoidosis: a comparative study of steroids and steroids plus immunosuppressive drugs.Int J Cardiol. 2019; 276 (Feb 1): 208-211https://doi.org/10.1016/j.ijcard.2018.11.131
- Efficacy and safety of methotrexate for the treatment of autoimmune virus-negative myocarditis: a case series.J Clin Rheumatol. 2018; (Sep 18)https://doi.org/10.1097/RHU.0000000000000897
- Lupus myocarditis: initial presentation and longterm outcomes in a multicentric series of 29 patients.J Rheumatol. 2017; 44 (Jan): 24-32https://doi.org/10.3899/jrheum.160493
- Targeting CD20+ B-lymphocytes in inflammatory dilated cardiomyopathy with rituximab improves clinical course: a case series.Eur Heart J Case Rep. 2019; 3 (Sep 1pii: ytz131)https://doi.org/10.1093/ehjcr/ytz131
- Cardiac autoimmunity: myocarditis.Adv Exp Med Biol. 2017; 1003: 187-221https://doi.org/10.1007/978-3-319-57613-8_10
- Intravenous immunoglobulin therapy for acute myocarditis in children and adults.Int Heart J. 2019; 60 (Mar 20): 359-365https://doi.org/10.1536/ihj.18-299
- Off-label use of intravenous immunoglobulin therapy in the treatment of lupus myocarditis: Two case reports and literature review.Rev Med Interne. 2017; 38 (Mar): 204-209https://doi.org/10.1016/j.revmed.2016.05.005
Cacciatore C, Riviere S, Cohen A, Gatfosse M, Ederhy S, Fain O, et al. Systemic sclerosis: Efficacy of intravenous immunoglobulins in severe cardiac involvement?. Rev Med Interne. 2018 Jul;39(7):594-6. 10.1016/j.revmed.2017.12.013.
- Intravenous immunoglobulin - indications and mechanisms in cardiovascular diseases.Autoimmun Rev. 2008; 7 (Jun): 445-452https://doi.org/10.1016/j.autrev.2008.04.001
- Successful control of scleroderma myocarditis using a combination of cyclophosphamide and methylprednisolone.Scand J Rheumatol. 2010; 39 (Aug): 349-350https://doi.org/10.3109/03009740903493741
- Cyclophosphamide restores heart function in a patient with lupus myocarditis.Isr Med Assoc J. 2005; 7 (Apr): 266-267
- Intravenous cyclophosphamide improves cardiac dysfunction in lupus myocarditis.Scand J Rheumatol. 2003; 32: 306-308https://doi.org/10.1080/03009740310003956
- Myocarditis of mixed connective tissue disease: favourable outcome after intravenous pulsed cyclophosphamide.Clin Rheumatol. 1999; 18: 85-87https://doi.org/10.1007/s100670050062
- Cardiac involvement of churg-strauss syndrome as a reversible cause of dilated cardiomyopathy.J Cardiovasc Ultrasound. 2015; 23 (Mar): 40-43https://doi.org/10.4250/jcu.2015.23.1.40
- A cohort study reveals myocarditis to be a rare and life-threatening presentation of large vessel vasculitis.Semin Arthritis Rheum. 2017; 47 (Oct): 241-246https://doi.org/10.1016/j.semarthrit.2017.03.023
- EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis.Ann Rheum Dis. 2016; 75 (SepErratum in: Ann Rheum Dis. 2017 Aug;76(8):1480): 1583-1594https://doi.org/10.1136/annrheumdis-2016-209133
- Role of metabolites of cyclophosphamide in cardiotoxicity.BMC Res Notes. 2017; 10 (Aug 14): 406https://doi.org/10.1186/s13104-017-2726-2
- Successful triple combination immunosuppressive therapy with prednisolone, cyclosporine, and mycophenolate mofetil to treat recurrent giant cell myocarditis.Intern Med. 2019; 58 (Jul 15): 2035-2039https://doi.org/10.2169/internalmedicine.2471-18
De Luca G, Cavalli G, Campochiaro C, Tresoldi M, Dagna L. Myocarditis: an interleukin-1- mediated disease?. Front. Immunol. 9:1335. 10.3389/fimmu.2018.01335.
- Formation of the inflammasome in acute myocarditis.Int J Cardiol. 2014; 171 (Feb 15): e119-e121https://doi.org/10.1016/j.ijcard.2013.12.137
- The heart on fire: inflammasome and cardiomyopathy.Exp Physiol. 2013; 98 (Feb): 385https://doi.org/10.1113/expphysiol.2012.069021
- Tumor necrosis factor alpha and interleukin 1beta are responsible for in vitro myocardial cell depression induced by human septic shock serum.J Exp Med. 1996; 183 (Mar 1): 949-958https://doi.org/10.1084/jem.183.3.949
- Targeting interleukin- 1 in heart disease.Circulation. 2013; 128 (Oct 22): 1910-1923https://doi.org/10.1161/CIRCULATIONAHA.113.003199
- Mechanism of cytokine inhibition of beta-adrenergic agonist stimulation of cyclic AMP in rat cardiacmyocytes. Impairment of signal transduction.Circ Res. 1990; 67 (Sep): 753-763https://doi.org/10.1161/01.RES.67.3.753
- Suppression of beta-adrenergic responsiveness of L-type Ca2+ current by IL-1beta in rat ventricular myocytes.Am J Physiol. 1999; 276 (Jan): H141-H148https://doi.org/10.1152/ajpheart.1999.276.1.H141
- Involvement of ceramide in inhibitory effect of IL-1 beta on L-type Ca2+ current in adult rat ventricular myocytes.Am J Physiol. 1997; 272 (Jun): H2591-H2598https://doi.org/10.1152/ajpheart.1997.272.6.H2591
- G protein-mediated suppression of L-type Ca2+ current by interleukin-1 beta in cultured rat ventricular myocytes.Am J Physiol. 1995; 268 (Feb): C339-C349https://doi.org/10.1152/ajpcell.1995.268.2.C339
- Chronic exposure to interleukin 1beta induces a delayed and reversible alteration in excitation-contraction coupling of cultured cardiomyocytes.Pflugers Arch. 2002; 445: 246-256
- Interleukin-1 blockade for the treatment of pericarditis.Eur Heart J Cardiovasc Pharmacother. 2018; 4 (Jan 1): 46-53https://doi.org/10.1093/ehjcvp/pvx018
- Enhanced interleukin-1 activity contributes to exercise intolerance in patients with systolic heart failure.PLoS One. 2012; 7: e33438https://doi.org/10.1371/journal.pone.0033438
- Effects of interleukin-1 blockade with anakinra on aerobic exercise capacity in patients with heart failure and preserved ejection fraction (from the D-HART pilot study).Am J Cardiol. 2014; 113 (Jan 15): 321-327https://doi.org/10.1016/j.amjcard.2013.08.047
- Interleukin-1 blockade in heart failure with preserved ejection fraction: rationale and design of the diastolic heart failure anakinra response trial 2 (D-HART2).Clin Cardiol. 2017; 40 (Sep): 626-632https://doi.org/10.1002/clc.22719
- Interleukin-1 blockade in acute decompensated heart failure: a randomized, double-blinded, placebo-controlled pilot study.J Cardiovasc Pharmacol. 2016; 67 (Jun): 544-551https://doi.org/10.1097/FJC.0000000000000378
- Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis.Circulation. 2008; 117 (May 20): 2662-2669https://doi.org/10.1161/CIRCULATIONAHA.107.731877
- Interleukin-1 receptor blockade rescues myocarditis-associated end-stage heart failure.Front Immunol. 2017; 8 (Feb 9): 131https://doi.org/10.3389/fimmu.2017.00131
- Treating life-threatening myocarditis by blocking interleukin-1.Crit Care Med. 2016; 44: e751-e754https://doi.org/10.1097/CCM.0000000000001654
- Refractory adult-onset Still disease complicated by macrophage activation syndrome and acute myocarditis: a case report treated with high doses (8 mg/kg/d) of anakinra.Medicine (Baltimore). 2017; 96 (Jun): e6656https://doi.org/10.1097/MD.0000000000006656
- Treating heart inflammation with interleukin-1 blockade in a case of erdheim–chester disease.Front Immunol. 2018; 9 (Jun 1): 1233https://doi.org/10.3389/fimmu.2018.01233
- Advances in potential targeted therapies for erdheim-chester disease.Expert Opin Orphan Drugs:. 2017; 5: 253-260https://doi.org/10.1080/21678707.2017.1285226
- Treatment of dilated cardiomyopathy with interleukin-1 inhibition.Ann Intern Med. 2018; 169 (Dec 4): 819-820https://doi.org/10.7326/L18-0315
- Canakinumab for the treatment of autoinflammatory recurrent fever syndromes.N Engl J Med. 2018; 378: 1908-1919https://doi.org/10.1056/NEJMoa1706314
- Efficacy of canakinumab as first-line biologic agent in adult-onset Still's disease.Arthritis Res Ther. 2019; 21 (Feb 13): 54https://doi.org/10.1186/s13075-019-1843-9
- Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions.Ann Rheum Dis. 2012; 71: 1839-1848https://doi.org/10.1136/annrheumdis-2011-200908
- Antiinflammatory therapy with canakinumab for atherosclerotic disease.N Engl J Med. 2017; 377: 1119-1131https://doi.org/10.1056/NEJMoa1707914
- Interleukin-6 spillover in the peripheral circulation increases with the severity of heart failure, and the high plasma level of interleukin-6 is an important prognostic predictor in patients with congestive heart failure.J Am Coll Cardiol. 1998; 31: 391-398https://doi.org/10.1016/S0735- 1097(97)00494-4
- Interleukin-6 and cardiovascular diseases.Jpn Heart J. 2004; 45 (Mar): 183-193https://doi.org/10.1536/jhj.45.183
- Interleukin-6 receptor inhibition modulates the immune reaction and restores titin phosphorylation in experimental myocarditis.Basic Res Cardiol. 2014; 109: 449https://doi.org/10.1007/s00395-014-0449-2
- Fulminant myocarditis and macrophage activation syndrome secondary to adult-onset Still's disease successfully treated with tocilizumab.Rheumatology (Oxford). 2014; 53 (Jul): 1352-1353https://doi.org/10.1093/rheumatology/keu019
- Macrophage-stimulated cardiac fibroblast production of IL-6 is essential for TGF β/Smad activation and cardiac fibrosis induced by angiotensin II.PLoS One. 2012; 7: e35144https://doi.org/10.1371/journal.pone.0035144
- Deletion of interleukin-6 alleviated interstitial fibrosis in streptozotocin-induced diabetic cardiomyopathy of mice through affecting TGFβ1 and miR-29 pathways.Sci Rep. 2016; 6 (Mar 14): 23010https://doi.org/10.1038/srep23010
- Tocilizumab for the treatment of myocardial inflammation shown by cardiac magnetic resonance: report of two cases and rationale for its therapeutic use.J Clin Rheumatol. 2019; (Nov 19)https://doi.org/10.1097/RHU.0000000000001194
- The benefits and prospects of interleukin-6 inhibitor systemic sclerosis.Mod Rheumatol. 2019; 29 (Mar): 294-301https://doi.org/10.1080/14397595.2018.1559909
- Serum interleukin-6 in systemic sclerosis and its correlation with disease parameters and cardiopulmonary involvement.Sarcoidosis Vasc Diffuse Lung Dis. 2016; 33 (Dec 23): 321-330
- Critical contribution of the interleukin-6/signal transducer and activator of transcription 3 axis to vasculopathy associated with systemic sclerosis.J Dermatol. 2017; 44 (Aug): 967-971https://doi.org/10.1111/1346-8138.13827
- Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial(faSScinate).Ann Rheum Dis. 2018; 77 (Feb): 212-220https://doi.org/10.1136/annrheumdis-2017-211682
- B cell depletion in diffuse progressive systemic sclerosis: safety, skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial.Arthritis Res Ther. 2010; 12: R54https://doi.org/10.1186/ar2965
- Tumour-associated antigens in systemic sclerosis patients with interstitial lung disease: association with lung involvement and cancer risk.Rheumatology (Oxford). 2015; 54: 1991-1999https://doi.org/10.1093/rheumatology/kev204
- Tocilizumab for the treatment of giant cell arteritis.Expert Rev Clin Immunol. 2018; 14 (May): 339-349https://doi.org/10.1080/1744666X.2018.1468251
- Tocilizumab in giant cell arteritis.Cardiol Rev. 2018; 26 (Nov/Dec): 321-330https://doi.org/10.1097/CRD.0000000000000204
- Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: american society of clinical oncology clinical practice guideline.J Clin Oncol. 2018; 36: 1714-1768https://doi.org/10.1200/JCO.2017.77.6385
- Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia [published online ahead of print, 2020 Mar 30].Nat Rev Cardiol. 2020; (10.1038/s41569-020-0348-1)https://doi.org/10.1038/s41569-020-0348-1
- Management of immunotherapy-related toxicities, version 1.2019.J Natl Compr Canc Netw. 2019; 17: 255-289https://doi.org/10.6004/jnccn.2019.0013
- Cardiotoxicity associated with CTLA4 and PD1 blocking immunotherapy.J Immunother Cancer. 2016; 4: 50https://doi.org/10.1186/s40425-016-0152-y
- Fulminant myocarditis with combination immune checkpoint blockade.N Engl J Med. 2016; 375: 1749-1755https://doi.org/10.1056/NEJMoa1609214
- Myasthenic crisis and polymyositis induced by one dose of nivolumab.Cancer Sci. 2016; 107: 1055-1058https://doi.org/10.1111/cas.12961
- Drug-induced myocarditis after nivolumab treatment in a patient with PDL1- negative squamous cell carcinoma of the lung.Lung Cancer. 2016; 99: 117-119https://doi.org/10.1016/j.lungcan.2016.06.025
- Acute lymphocytic myocarditis with anti-PD-1 antibody nivolumab.Circ Heart Fail. 2016; 9e003514https://doi.org/10.1161/CIRCHEARTFAILURE.116.003514
- Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2018; 29 (iv264–iv266)https://doi.org/10.1093/annonc/mdy162
- Clinical features, management, and outcomes of immune checkpoint inhibitor-related cardiotoxicity.Circulation. 2017; 136: 2085-2087https://doi.org/10.1161/CIRCULATIONAHA.117.030571
- Myocarditis in patients treated with immune checkpoint inhibitors.J Am Coll Cardiol. 2018; 71: 1755-1764https://doi.org/10.1016/j.jacc.2018.02.037
- Immune checkpoint inhibitors and cardiovascular toxicity.Lancet Oncol. 2018; 19: e447-e458https://doi.org/10.1016/S1470-2045(18)30457-1
- Smoldering myocarditis following immune checkpoint blockade.J Immunother Cancer. 2017; 5: 91https://doi.org/10.1186/s40425-017-0296-4
- Autoimmune myocarditis caused by immune checkpoint inhibitors treated with antithymocyte globulin.J Immunother. 2018; 41: 332-335https://doi.org/10.1097/CJI.0000000000000239
- Successful use of equine anti-thymocyte globulin (ATGAM) for fulminant myocarditis secondary to nivolumab therapy.Br J Cancer. 2017; 117: 921-924https://doi.org/10.1038/bjc.2017.253
- Progressive and reversible conduction disease with checkpoint inhibitors.Can J Cardiol. 2017; 33 (1335.e13–1335.e15)https://doi.org/10.1016/j.cjca.2017.05.026
- Cardiovascular toxicities associated with cancer immunotherapies.Curr Cardiol Rep. 2017; 19: 21https://doi.org/10.1007/s11886-017-0835-0
- Immune checkpoint inhibitor-associated myocarditis: a new challenge for cardiologists.Can J Cardiol. 2018; 34 (92.e1–92.e3)https://doi.org/10.1016/j.cjca.2017.09.025
- Cardiac toxicity associated with immune checkpoint inhibitors: case series and review of the literature.Case Rep Oncol. 2019; 12: 260-276https://doi.org/10.1159/000498985
- Abatacept for severe immune checkpoint inhibitor-associated myocarditis.N Engl J Med. 2019; 380: 2377-2379https://doi.org/10.1056/NEJMc1901677
- Alemtuzumab for immune-related myocarditis due to PD-1 therapy.N Engl J Med. 2019; 380: 2375-2376https://doi.org/10.1056/NEJMc1903064
Article info
Publication history
Published online: May 10, 2020
Accepted:
April 20,
2020
Received in revised form:
April 16,
2020
Received:
February 15,
2020
Identification
Copyright
© 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
