Comparison of the early and late CAE cases from three cardio-oncology units
| Early CAE cases | Late CAE cases | P value | ||||
| n avail | Value | n avail | Value | Proportion (95% CI) | ||
| Number of cases | 19 | 19 | ||||
| Male | 15 | 10 (66.7) | 19 | 15 (78.9) | (56.1% to 92.0%) | 0.68 |
| Age (years) | 15 | 71 (67–76) | 19 | 70 (65–74) | – | 0.33 |
| Previous cardiovascular disease | 15 | 5 (33.3) | 19 | 7 (36.8) | (19% to 59.1%) | 1 |
| Cardiovascular risk factors | 15 | 9 (60.0) | 19 | 19 (100.0) | (80.2% to 100%) | 0.01 |
| Dyslipidemia | 15 | 3 (20.0) | 19 | 10 (52.6) | (31.7% to 72.7%) | 0.11 |
| Hypertension | 15 | 6 (40.0) | 19 | 11 (57.9) | (36.2% to 76.9%) | 0.49 |
| Tobacco | 15 | 3 (20.0) | 19 | 13 (68.4) | (45.8% to 84.8%) | 0.01 |
| Type 2 diabetes | 15 | 1 (6.7) | 19 | 4 (21.1) | (8.0% to 43.9%) | 0.49 |
| Cancer | 19 | 19 | 0.01 | |||
| Melanoma | 3 (15.8) | 1 (5.3) | (0% to 26.5%) | |||
| Non-small cell lung cancer | 8 (42.1) | 17 (89.5) | (67.4% to 98.3%) | |||
| Renal cancer | 2 (10.5) | 1 (5.3) | (0% to 26.5%) | |||
| Other cancers | 6 (31.6) | 0 (0.0) | (0% to 19.8%) | |||
| ICI therapy | 15 | 19 | 0.16 | |||
| Atezolizumab | 2 (13.3) | 0 (0.0) | (0% to 19.8%) | |||
| Nivolumab | 8 (53.3) | 16 (84.2) | (61.6% to 95.3%) | |||
| Pembrolizumab | 2 (13.3) | 1 (5.3) | (0% to 26.5%) | |||
| Nivolumab+ipilimumab | 3 (20.0) | 1 (5.3) | (0% to 26.5%) | |||
| Anti-PD-1 or anti-PD-L1 | 15 | 15 (100.0) | 19 | 19 (100.0) | (80.2% to 100%) | NA |
| Anti-CTLA-4 | 15 | 3 (20.0) | 19 | 1 (5.3) | (0% to 26.5%) | 0.43 |
| Combination therapy | 15 | 3 (20.0) | 19 | 1 (5.3) | (73.5% to 100%) | 0.43 |
| Time to onset after initiation of ICI (days) | 15 | 14 (8–62) | 19 | 304 (180–422) | – | <0.001 |
| Total number of infusions before cardiotoxicity, n | 15 | 1 (1–3) | 17 | 11 (7–17) | – | <0.001 |
| Initial clinical cardiovascular manifestations | ||||||
| Cardiopulmonary failure | 15 | 0 (0.0) | 19 | 1 (5.3) | (0% to 26.5%) | 1 |
| Chest pain | 15 | 2 (13.3) | 19 | 0 (0.0) | (0% to 19.8%) | 0.36 |
| HF symptoms | 15 | 8 (53.3) | 19 | 13 (68.4) | (45.8% to 84.8%) | 0.59 |
| Cough | 15 | 1 (6.7) | 19 | 1 (5.3) | (0% to 26.5%) | 1 |
| Dyspnea | 15 | 8 (53.3) | 19 | 13 (68.4) | (45.8% to 84.8%) | 0.59 |
| Left HF | 15 | 8 (53.3) | 19 | 12 (63.2) | (40.9% to 81%) | 0.82 |
| Orthopnea | 15 | 0 (0.0) | 19 | 1 (5.3) | (0% to 26.5%) | 1 |
| Right HF | 15 | 0 (0.0) | 19 | 3 (15.8) | (4.7% to 38.4%) | 0.32 |
| Palpitations | 15 | 5 (33.3) | 19 | 1 (5.3) | (0% to 26.5%) | 0.09 |
| ECG | ||||||
| Abnormal ECG | 14 | 7 (50.0) | 18 | 8 (44.4) | (24.5% to 66.3%) | 1 |
| Conduction disorder | 14 | 2 (14.3) | 18 | 3 (16.7) | (5% to 40%) | 1 |
| Prolonged PR interval | 14 | 0 (0.0) | 18 | 1 (5.6) | (0% to 27.6%) | 1 |
| Left anterior fascicular block | 14 | 1 (7.1) | 18 | 0 (0.0) | (0% to 20.7%) | 0.9 |
| BBB or non-specific intraventricular block | 14 | 2 (14.3) | 18 | 2 (11.1) | (1.9% to 34%) | 1 |
| Repolarization disorder | 14 | 5 (35.7) | 18 | 4 (22.2) | (8.5% to 45.7%) | 0.66 |
| Premature ventricular contractions | 14 | 0 (0.0) | 18 | 1 (5.6) | (0% to 27.6%) | 1 |
| Associated immune-related adverse events | 15 | 1 (6.7) | 19 | 7 (36.8) | (19% to 59.1%) | 0.1 |
| Type of cardiotoxicity | ||||||
| Acute coronary syndrome | 19 | 1 (5.3) | 19 | 0 (0.0) | (0% to 19.8%) | 1 |
| Atrial flutter or atrial fibrillation | 19 | 9 (47.4) | 19 | 2 (10.5) | (1.7% to 32.6%) | 0.03 |
| Cardiac arrest | 19 | 1 (5.3) | 19 | 1 (5.3) | (0% to 26.5%) | 1 |
| Cardiogenic shock | 19 | 0 (0.0) | 19 | 1 (5.3) | (0% to 26.5%) | 1 |
| Ejection fraction decreased | 19 | 7 (36.8) | 19 | 14 (73.7) | (50.9% to 88.5%) | 0.05 |
| HF | 19 | 1 (5.3) | 19 | 9 (47.4) | (27.3% to 68.3%) | 0.01 |
| Isolated right BBB | 19 | 0 (0.0) | 19 | 1 (5.3) | (0% to 26.5%) | 1 |
| Myocarditis | 19 | 8 (42.1) | 19 | 2 (10.5) | (1.7% to 32.6%) | 0.06 |
| Pericardial effusion | 19 | 2 (10.5) | 19 | 2 (10.5) | (1.7% to 32.6%) | 1 |
| Takotsubo like syndrome | 19 | 3 (15.8) | 19 | 0 (0.0) | (0% to 19.8%) | 0.23 |
| Increased brain natriuretic peptide level | 13 | 7 (53.8) | 17 | 11 (64.7) | (41.2% to 82.8%) | 0.82 |
| Increased troponin | 19 | 12 (63.2) | 18 | 9 (50.0) | (29% to 71%) | 0.63 |
| Echocardiogram | ||||||
| Normal LVEF at baseline | 12 | 11 (91.7) | 11 | 11 (100.0) | (70% to 100%) | 1 |
| Diastolic dysfunction | 15 | 1 (6.7) | 18 | 3 (16.7) | (5% to 40%) | 0.73 |
| Dilated left ventricle | 15 | 0 (0.0) | 18 | 1 (5.6) | (0% to 27.6%) | 1 |
| Dilated right atrium | 7 | 0 (0.0) | 11 | 2 (18.2) | (4% to 48.8%) | 0.67 |
| Dilated right ventricle | 15 | 0 (0.0) | 18 | 1 (5.6) | (0% to 27.6%) | 1 |
| Dys-synchrony of the left ventricle | 15 | 0 (0.0) | 18 | 1 (5.6) | (0% to 27.6%) | 1 |
| Ejection fraction decreased | 19 | 7 (36.8) | 19 | 14 (73.7) | (50.9% to 88.5%) | 0.05 |
| Global longitudinal strain | 5 | −13 (−13 to −12) | 5 | −12 (−14 to −12) | – | 0.92 |
| Right ventricle dysfunction | 15 | 0 (0.0) | 18 | 1 (5.6) | (0% to 27.6%) | 1 |
| Systolic pulmonary artery pressure increased | 15 | 0 (0.0) | 18 | 9 (50.0) | (29% to 71%) | 0.005 |
| Thickened interventricular septum | 15 | 1 (6.7) | 18 | 0 (0.0) | (0% to 20.7%) | 0.93 |
| Coronary angiogram ruling out ischemic event | 7 | 6 (85.7) | 14 | 14 (100.0) | (74.9% to 100%) | 0.72 |
| Non-invasive perfusion test normal | 0 | – | 1 | 1 (100.0) | (16.7% to 100%) | NA |
| MRI | ||||||
| Infarction scar | 9 | 0 (0.0) | 14 | 1 (7.1) | (0% to 33.5%) | 1 |
| Late gadolinium enhancement | 9 | 4 (44.4) | 14 | 1 (7.1) | (0% to 25.1%) | 0.11 |
| Myocardial edema | 9 | 4 (44.4) | 14 | 0 (0.0) | (0% to 33.5%) | 0.03 |
| MRI suggestive of myocarditis | 9 | 6 (66.7%) | 14 | 1 (7.1%) | (0% to 33.5%) | 0.01 |
| Treatment and follow-up | 15 | 19 | (80.2% to 100%) | |||
| Anti-inflammatory therapies | ||||||
| Corticosteroids | 15 | 6 (40.0) | 19 | 10 (52.6) | (31.7% to 72.7%) | 0.7 |
| Cardiac medications | ||||||
| Amiodarone | 15 | 4 (26.7) | 19 | 1 (5.3) | (0% to 26.5%) | 0.21 |
| ACE inhibitors | 15 | 5 (33.3) | 19 | 10 (52.6) | (31.7% to 72.7%) | 0.44 |
| Aspirin | 15 | 1 (6.7) | 19 | 0 (0.0) | (0% to 19.8%) | 0.9 |
| Beta blockers | 15 | 7 (46.7) | 19 | 11 (57.9) | (36.2% to 76.9%) | 0.76 |
| Flecainide | 15 | 1 (6.7) | 19 | 0 (0.0) | (0% to 19.8%) | 0.9 |
| Ivabradine | 15 | 0 (0.0) | 19 | 1 (5.3) | (0% to 26.5%) | 1 |
| Statins | 15 | 1 (6.7) | 19 | 0 (0.0) | (0% to 19.8%) | 0.9 |
| LVSD completely reversible | 8 | 3 (37.5) | 14 | 2 (14.3) | (2.8% to 41.2%) | 0.47 |
| Interruption of ICI therapy | 14 | 9 (64.3) | 18 | 15 (83.3) | (60% to 95%) | 0.41 |
| Cardiovascular death | 15 | 1 (6.7) | 19 | 2 (10.5) | (1.7% to 32.6%) | 1 |
| All-cause death | 15 | 6 (40.0) | 19 | 8 (42.1) | (23.1% to 63.8%) | 1 |
Data are n (%) or median (IQR).
BBB, bundle branch block; CAE, cardiac adverse event; CTLA-4, cytotoxic T-lymphocyte antigen 4; HF, heart failure; ICI, immune checkpoint inhibitor; LVEF, left ventricular ejection fraction; LVSD, left ventricular systolic dysfunction; NA, test is not applicable; n avail, number of cases with available data; PD-1, programmed death 1; PD-L1, programmed death ligand 1.