Myocarditis presentation and clinical course
| IIST (n=36) | No IIST (n=24) | P value | |
| Time from beginning ICI to onset myocarditis, days* | 18 (12–30) | 60 (20–101) | 0.002 |
| Clinical presentation | |||
| Chest pain | 4 (11) | 3 (13) | 1.0 |
| Shortness of breath | 22 (61) | 11 (46) | 0.24 |
| Palpitations | 5 (14) | 1 (4) | 0.39 |
| Pericardial effusion | 1 (3) | 0 (0) | 1.0 |
| Asymptomatic troponin elevation | 7 (19) | 8 (33) | 0.22 |
| ECG on admission | |||
| Atrial fibrillation | 8 (22) | 3 (13) | 0.50 |
| Ventricular tachycardia | 4 (11) | 1 (4) | 0.64 |
| Complete atrioventricular block† | 12 (34) | 0 (0) | 0.002 |
| Complete left bundle branch block† | 3 (9) | 2 (8) | 1.0 |
| Complete right bundle branch block† | 8 (23) | 2 (8) | 0.29 |
| T wave or ST segment abnormality† | 8 (23) | 3 (13) | 0.51 |
| LVEF on admission, %‡ | 50±14 | 55±12 | 0.12 |
| CMR | |||
| Performed | 20 (56) | 20 (83) | 0.03 |
| Myocarditis-CMR diagnosis | 18 (90) | 19 (95) | 1.0 |
| Elevated troponin‡ | 32 (89) | 17 (71) | 0.02 |
| Endomyocardial biopsy | |||
| Performed | 10 (28) | 0 (0) | 0.004 |
| Positive for myocarditis | 9 (90) | – | – |
| Myocarditis diagnosis | |||
| Definite | 25 (69) | 14 (58) | 0.35 |
| Probable | 6 (17) | 3 (13) | |
| Possible | 5 (14) | 7 (29) | |
| Myocarditis grade§ | |||
| Grade 1 | 0 (0) | 0 (0) | 0.017 |
| Grade 2 | 0 (0) | 4 (17) | |
| Grade 3 | 0 (0) | 1 (4) | |
| Grade 4 | 36 (100) | 19 (79) | |
| Myocarditis-related complications | |||
| Cardiogenic shock | 7 (19) | 0 (0) | 0.03 |
| Ventricular tachycardia or complete atrioventricular block | 15 (42) | 1 (4) | 0.001 |
| Sustained ventricular arrhythmia | 8 (22) | 1 (4) | 0.04 |
| Complete atrioventricular block | 15 (42) | 1 (4) | 0.002 |
| Other irAEs | |||
| Any irAEs | 29 (81) | 6 (25) | <0.0001 |
| Myositis | 24 (67) | 4 (17) | 0.0002 |
| Myasthenia gravis | 12 (33) | 1 (4) | 0.009 |
| Dermatitis | 4 (11) | 0 (0) | 0.14 |
| Thyroiditis | 3 (8) | 1 (4) | 1.0 |
| Polyradiculoneuritis | 2 (6) | 0 (0) | 0.51 |
| Arthritis | 0 (0) | 1 (4) | 0.40 |
| Uveitis | 1 (3) | 0 (0) | 1.0 |
| Corticosteroids | 33 (92) | 21 (88) | 0.60 |
| Time from first irAEs to corticosteroids, days¶ | 1 (1–2) | 1 (1–1) | 0.71 |
| Initial supportive therapy | |||
| Mechanical ventilation | 12 (33) | 2 (8) | 0.03 |
| Diuretics** | 4 (13) | 6 (25) | 0.31 |
| Beta-blockers‡ | 6 (19) | 7 (29) | 0.16 |
| Angiotensin-converting enzyme inhibitors* | 3 (9) | 8 (33) | 0.04 |
| Inotropic agents or vasopressors | 7 (19) | 0 (0) | 0.04 |
| Mechanical assist device | 3 (8) | 0 (0) | 0.27 |
| Pacing | 12 (33) | 0 (0) | 0.0008 |
| Study outcomes | |||
| Death from any cause | 18 (50) | 5 (21) | 0.02 |
| Death from cardiovascular cause | 7 (19) | 1 (4) | 0.13 |
Values are mean±SD, median (IQR), or n (%).
*Thirty-three of the 36 IIST patients had this information.
†Thirty-five of the 36 IIST patients had this information.
‡Thirty-two of the 36 IIST patients had this information.
§According to the ASCO guidelines.13
¶Seventeen of the 36 IIST patients had this information.
**Thirty of the 36 IIST patients had this information.
ASCO, American Society of Clinical Oncology; CMR, cardiovascular MR; ICI, immune checkpoint inhibitor; IIST, intensified immunosuppressive therapy; irAEs, immune-related adverse events; LVEF, left ventricular ejection fraction.