Table 1.
Case reports published from 2021–2022—ICI-related myocarditis.
| Study | Patient Characteristics | Medical History | Symptoms | Diagnosis | CV Side Effect | ICI | Type of Cancer | Myocarditis Onset | Myocarditis Treatment | Evolution |
|---|---|---|---|---|---|---|---|---|---|---|
| Ida, 2022 | ♀, 81 | HBP dyslipidemia |
high-grade fever whole-body rash altered consciousness |
↑CK; ↑CKMB, troponin I, C-reactive protein, ECG, TTE CMR endomyocardial biopsy |
Myocarditis | PD-L1i + PD-1i | advanced melanoma, | 1 week | Methylprednisolone followed by prednisolone IGIV |
favorable |
| Nguyen, 2022 | ♂, 25 | N/A | chest pain, subtle myalgia | Coronary angiography cardiac MRI endomyocardial biopsy Troponin-T creatine-kinase |
Myocarditis myositis |
PD-1i | hymoma | 2 weeks | Methylprednisolone mycophenolate-mofetil loading dose of intravenous abatacept oral ruxolitinib |
cardiogenic shock VT extracorporeal life support On day 40, the patient fully recovered clinically |
| Okauchi, 2022 | ♂, 60 | Smoking history | Cough, dyspnea | Chest RX BNP TTE |
Myocarditis | PD-1i | Squamous cell carcinoma | 130 weeks from initiation | Diuretics, beta-blocker | Favorable |
| Zhou, 2022 | ♂, 67 | N/A | fever, chest pain and dyspnea | Chest computed tomography, TTE, ECG, BNP, troponin T, CK | myocarditis | PD-L1i | lung squamous cell carcinoma stage IV |
days after lastcycle | methylprednisolone | favorable |
| Zhao, 2022 | ♂, 60 | N/A | fever, tachycardia, hypotension, fatigue, dyspnea | ECG, TTE |
Myocarditis + hypothyroidism | PD-1i | soft tissue sarcoma | 8 weeks | IV mPSL | favorable |
| Lorente-Ros, 2022 | ♂, 70 | nephrectomy | 2 episodes in the previous 12 h of severe dizziness, dyspnea, and profuse sweating. | ECG troponin I,C- reactive protein, TTE ECG- 3rd AVB, coronary angiography, brain CT autoimmunity lab tests, brain, MRI, lumbar puncture, EEG |
Myocarditis + Encephalitis | PD-1i + CTLA-4i | renal cell carcinoma | 19 days | Temporary pacemaker high-dose iv corticosteroids intravenous immunoglobulins |
delirium deterioration in his level of consciousness, intubation. Extubate -> reintubation discharged |
| Saishu 2022 | ♀, 55 | N/A | quadrantanopia, ocular motility disorder, diplopia, dysphagia, ocular motility disorder, muscle weakness of the extremities, bilateral ptosis muscle weakness. |
↑CK; ECG, TTE; anti-AchR ab. |
Myocarditis, myositis/MG | PD-1i | mela- noma |
2 weeks | IGIV, prednisolone Intubation for MV, mPSL plasma exchange Tracheostomy |
favorable |
| Yang, 2022 | ♀, 51 | contrast agent allergy | high fever, mild dyspnea, and systemic rash. |
Liver function indexes cardiac markers CT examination |
myocarditis hepatitis |
PD-1i | breast cancer (TNBC) | 3 days | Iv methylprednisolone Antibiotics hepatic protectors |
favorable |
| Ederhy, 2021 | ♀, 60–70 approx. | N/A | diplopia | ↑TnI; ECG; CMR, coronary angiography, EMB |
Myocarditis (subclinical) | PD-1i | Lung cancer (unmentioned type, metastatic) | 3 infusions + 10 days | steroids, plasmapheresis | favorable |
| Tsuruda, 2021 | ♂, 75 | N/A | asymptomatic | ↑cTnT, CK, CK-MB; ECG, Echocardiogram, CMR, EMB | Myocarditis (subclinical), TTS | PD-1i | NSCLS (squamous, recurrent) | 3 weeks | mPSL | fatal |
| ♂, 47 | N/A | asymptomatic | ↑cTnT, CK, CK-MB; CMR | Myocarditis (subclinical) | PD-1i | Ethmoid sinus cancer | 3 infusions + 16 days | mPSL; IVIG (progressive thrombocytopenia); cyclosporine (hemophagocytic syndrome) | favorable | |
| ♂, 63 | N/A | hypotension (84/42 mmHg), tachycardia (132 bpm), tachypnea (22 rpm); high fever, decreased appetite, | ↑cTnT, CK, AST, ALT, CRP, Cr; ↓WBC, Hb, PLT; ECG, Echocardiogram |
cardiac complication of cytokine-releasing syndrome | PD-1i | Hypopharyngeal cancer | 5 infusions + 32 days | cardioversion, extracorporeal hemoperfusion with polymyxin B + continuous hemodiafiltration, catechocardiographylamines, broad-spectrum antibiotics, recombinant thrombomodulin, IVIG, high-dose corticosteroids | favorable | |
| Tanabe, 2021 | ♂, 75 | N/A | posterior neck pain, neck drop | ↑TnI, CK, CK-MB; ↑Eo (834/μL), ↓eRFG; DLST (+); Echocardiogram, coronary angiography, CMR, | Myocarditis (subclinical) | PD-1i + CTLA-4i | RCC (clear cell, metastatic) | 53 days | prednisolone | favorable |
| Barham, 2021 | ♀, 79 | N/A | dizziness, abdominal bloating, hypoxic | ↑LDH; ECG; EMB |
Myocarditis (grade 4); hyperprogression | PD-1i + CTLA-4i | Melanoma (vaginal, metastatic) | 23 days | steroids; carboplatin + paclitaxel (salvage therapy), atropine, pacemaker (for AVB III) | fatal |
| Xie, 2021 | ♂, 67 | N/A | exertional dyspnea, ptosis, blurred vision, quadriparesis | ↑TnI, CK, CK-MB, AST, ALT, BNP, Mb; ECG; Echocardiogram; coronary angiography |
Myocarditis (fulminant), MG crisis, hepatic dysfunction; delayed ir pneumonitis | PD-1i + pemetrexed + carboplatin | LCNEC (metastatic) | 2 weeks | mPSL; pacemaker (temporary permanent); ganciclovir/cefmetazole | favorable |
| Hu, 2021 | ♂, 63 | N/A | chest tightness, limb weakness, dorsal myasthenia, diplopia, dysphagia |
↑Hs-TnI, CK-MB, NT-proBNP, CK; Echocardiogram, CMR; anti-β1AR ab, CC ab, anti-myosin heavy chain ab, ribonucleoprotein ab |
Myocarditis + MG | PD-1i | ureteral urothelial cancer IV | 3 weeks | mPSL IVIG |
favorable |
| Wintersperger, 2021 | ♂, 52 | N/A | fatigue dyspnea | ↑hsTnI, CK, BNP; ECG, Chest CT, Echocardiogram, CMR, EMB |
Myocarditis | PD-L1i + investigational ICI | melanoma | 3 weeks | mPSL prednisone infliximab IV MMF |
favorable |
| ♀, 60 | N/A | general- ized weakness muscle pain fatigue fever |
↑CK, hsTnI; ECG, Coronary angiography, CMR, EMB |
Myocarditis | PD-L1i | gynecological cancer | 2 weeks | mPSL prednisone |
favorable | |
| ♀, 49 | N/A | fever cough | ↑hsTnI, BNP; chest CT, ECG, CMR |
Myocarditis | PD-L1i | triple-negative breast cance | 2 weeks | MMF prednisone |
favorable | |
| ♀, 74 | N/A | general pain, progressive muscle weakness diplopia | ↑hsTnI, BNP, ECG, Coronary angiography, CMR |
Myocarditis | PD-L1i | gynecological cancer | 2 weeks | mPSL prednisone MMF |
favorable | |
| Stein-Merlob, 2021 | ♀, 60 | N/A | palpitations reduced exercise tolerance, cool extremities altered mental status |
↑Tn, BNP; ECG, Echocardiogram, Coronary angiography, CMR |
Myocarditis Ocular myasthenia, Colitis hepatitis |
PD-1i | Colon cancer | Metoprolol succinate, lisinopril Continued immunosuppression spironolactone, Oral amiodarone, wearable defibrillator.dopamine Nitroprusside milrinone, VA-ECMO |
favorable | |
| Shen, 2021 | ♀, 53 | N/A | cough chest congestion, muscle weakness fatigability drooping eyelids, |
↑CK, CK-MB; ECG |
Myocarditis, hepatitis, renal dysfunction, hypothyroidism | PD-1i + paclitaxel + platinum |
type B3 thymoma | 3 weeks | Magnesium isoglycyrrhizinate reduced glutathione injections, prednisone mPSL euthyrox pyridostigmine |
favorable |
| Miyauchi, 2021 | ♂, 71 | hypertension, DM2, hyperuricemia | Asymptomatic, chest tightness, shortness of breath, cardiogenic shock |
↑CK, CM-MB, TnI, NT-proBNP; ECG, catheterization, EMB, CMR |
Myocarditis | CTLA-4i + PD-1i | RCC | 8 weeks | dopamine, dobutamine, noradrenaline intra-aortic balloon pump was inserted, adaptive servo ventilation mPSL prednisolone |
favorable |
| Luo, 2021 | ♀, 47 | N/A | diplopia, myalgia, limb weakness, dysphagia, dyspnea | ↑TnI, CK, ECG, EMG; RyR-ab, AChR-ab, anti-fibrillarin ab, anti-NOR-90 ab anti-Ro-52 ab |
Myocarditis, myositis, MG | PD-1i | thymoma | 3 weeks | neostigmine IVIG mPSL prednisolone pacemaker |
favorable |
| Li, 2021 | ♂, 62 | hypertension, coronary heart disease | fever lethargy, cognitive dysfunction tachypnea hypoxia hypotension oliguria |
↑Mb, Tn, CK-MB; ECG | cardiotoxicity kidney toxicity. | PD-1i | lung adenocarcinoma | 48 weeks | mPSL continuous renal replacement therapy |
favorable |
| Jespersen, 2021 | ♂, 57 | N/A | headache myalgia, palpitations binocular diplopia, ptosis, muscle weakness |
↑TnI, CK-MB, Mb, CK; ECG, EMG, Echocardiogram, CMR, AChR-ab, |
Myocarditis + myositis | CTLA-4i + PD-1i | RCC | 2 weeks | temporary pacemaker. mPSL abatacept MMF implantable cardio-defibrilator |
favorable |
| Iwasaki, 2021 | ♀, 70 | hypertension, aortic stenosis, chronic renal failure |
shortness of breath fatigue | ↑CK, CK-MB, TnT, NT-proBNP; ECG, Echocardiogram, CMR, Cardiac catheterization, EBMCoronary angiography |
Myocarditis + myositis | PD-L1i | HCC | <1 week | cariperitide, furosemide, mPSL prednisolone |
favorable |
| Hernández, 2021 | ♀, 48 | N/A | shortness of breath, dyspnea, bilateral ptosis blurred vision |
↑Hs-TnI, NT-proBNP, CRP, CK; ECG, Echocardiogram, Coronary angiography, EMB; AChR-ab |
Myocarditis + myositis (MG) | PD-1i | thymoma | <2 weeks | IV isoproterenol drip mPSL Infliximab temporary pacemaker, dual-chamber pacemaker. intravenous amiodarone, noradrenaline dobutamine, intravenous anti-thymocyte globuline, pyridostigmine, ECMO |
fatal |
| Giblin, 2021 | ♀, 47 | N/A | dermatitisdiarrhea, palpitations | ↑hS-TnI, BNP, Echocardiogram, CMR, Coronary angiography, EMB |
Myocarditis (subclinical) | CTLA-4i + PD-1i | melanoma | 1 week | mPSL prednisolon, IVIG |
favorable |
| Cao, 2021 | ♂, 69 | N/A | ptosis, diplopia, shortness of breath, | ↑CK, CK-MB, Mb, hs-TnT, NT-proBNP, LDH, ECG; Echocardiogram, EMG |
Myositis, Myocarditis SJS/TEN |
PD-1i | esophagogastric junction carcinoma |
2 weeks | mPSL IVIG plasmapheresis |
favorable |
| Ai, 2021 | ♂, 72 | N/A | asymptomatic | ECG; CMR | Myocarditis (DRESS) | PD-1i | gastric adenocarcinoma | 3 weeks | SCS (for DRESS) |
Abbreviations: ↑, increase; ↓, decrease; Ab, antibody; ACEi, angiotensin-converting-enzyme inhibitors, AchR, acetylcholine receptor, AF, atrial fibrillation; ALT, alanine transaminase, ANA, antinuclear antibodies, ARB, angiotensin receptor blockers; AST, aspartate aminotransferase, AVB, atrioventricular block; β1AR, beta-1-adrenergic receptor; BB, beta-blocker; BiPAP, bilevel positive airway pressure; BNP, brain natriuretic peptide; CAD, coronary artery disease; CC, calcium channel; CK, creatine kinase; CK-MB, creatine kinase—muscle/brain; CMR, cardiovascular magnetic resonance imaging; cN1A, cytosolic 5’-nucleotidase 1A; Cr, serum creatinine; CRP, C-reactive protein; CT, computer tomography; CTLA-4i, cytotoxic T-lymphocyte-associated protein 4 inhibitor; DLST, drug lymphocyte stimulation test; DM2, diabetes mellitus type 2; ECG, electrocardiography; eGFR, estimated glomerular filtration rate; EMB, endomyocardial biopsy; Eo, eosinophils; ESC, esophageal squamous cell carcinoma; GFAP, glial fibrillary acidic protein, Hb, hemoglobin; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HCQ, hydroxychloroquine; HMGCR, HMG-CoA reductase; HF, heart failure; HfpEF, heart failure with preserved ejection fraction; IABP, intra-aortic balloon pump; ICD, implantable cardioverter-defibrillator; IV, intravenous; IVIG, intravenous immune globulin; LCNEC, large cell neuroendocrine carcinoma; LDH, lactate dehydrogenasem; LyT, T lymphocytes; Mb, myoglobin; MPM, malignant pleural mesothelioma; mPSL, methylprednisolone; MG, myasthenia gravis; MMF, mycophenolate mofetil; MuSK, muscle-specific kinase; MV, mechanical ventilation; NC, nasal cannula; NG, nasogastric; NIPPV, nasal intermittent positive pressure ventilation; NOR90, nucleolus organizer region; NSCLC, non-small cell lung cancer; NT-pro-BNP, N-terminal pro hormone BNP; PO, per oral; PD-1i, programmed cell death 1 inhibitor; PD-L1i, programmed cell death ligand 1 inhibitor; PLEX, plasmapheresis; PLT, platelet count; PM/SCL, polymyositis/scleroderma; RCC, renal cell carcinoma; RYR, ryanodine receptor; SCS, systemic corticosteroid therapy; SJS, Stevens-Johnson syndrome; SRP, signal recognition particle; TEN, toxic epidermal necrolysis; Tn, troponin; TTS, Takotsubo syndrome, VA ECMO, veno-arterial extracorporeal membrane oxygenation, VT, ventricular tachicardia, WBC, white blood cells count.