TABLE 3.
Comparison of Myocarditis Cases With and Without MACE
| No MACE (n = 19) |
MACE (n = 16) | p Value | |
|---|---|---|---|
| Age at start of ICI, yrs | 66.0 ± 13.2 | 63.0 ± 13.6 | 0.44 |
| Female | 6 (32.0) | 4 (25.0) | 0.72 |
| ICI to onset of myocarditis | 57 (6–235) | 31 (4–151) | 0.135 |
| Number of ICI doses | 5.2 ± 8 | 3 ± 3 | 0.40 |
| CV risk factors | |||
| Current or prior smoking | 7 (37.0) | 8 (50.0) | 0.51 |
| Hypertension | 14 (74.0) | 11 (69.0) | 1.00 |
| Diabetes mellitus | 7 (37.0) | 5 (31.0) | 1.00 |
| Single agent vs. combined | |||
| Combination (current regiment) | 9 (47.0) | 3 (19.0) | 0.08 |
| Monotherapy (current regiment) | 10 (53.0) | 13 (81.0) | |
| Type of combined ICI | |||
| Ipilimumab + Nivolumab | 6 (32.0) | 3 (19.0) | 0.46 |
| Ipilimumab + Pembrolizumab | 1 (5.3) | 0 (0.0) | 1.00 |
| Tremelimumab + Avelumab | 1 (5.3) | 0 (0.0) | 1.00 |
| Tremelimumab + Durvalumab | 1 (5.3) | 0 (0.0) | 1.00 |
| Type of monotherapy ICI* | |||
| Pembrolizumab | 9 (47.0) | 2 (13.0) | 0.035 |
| Nivolumab | 0 (0.0) | 7 (44.0) | 0.002 |
| Ipilimumab | 1 (5.3) | 1 (6.3) | 1.00 |
| Tremelimumab | 0 (0.0) | 1 (6.3) | 0.46 |
| Atezolizumab | 0 (0.0) | 2 (13.0) | 0.20 |
| Avelumab | 0 (0.0) | 0 (0.0) | – |
| Durvalumab | 0 (0.0) | 0 (0.0) | – |
| Overall types of ICI | |||
| Any anti-PD1 | 16 (84.0) | 12 (75.0) | 0.68 |
| Any anti-CTLA4 | 12 (63.0) | 6 (38.0) | 0.19 |
| Any anti-PDL1 | 2 (11.0) | 2 (13.0) | 1.00 |
| Pembrolizumab | 11 (58.0) | 5 (31.0) | 0.18 |
| Nivolumab | 6 (32.0) | 10 (63.0) | 0.07 |
| Ipilimumab | 10 (53.0) | 5 (31.0) | 0.31 |
| Tremelimumab | 2 (10.5) | 1 (6.3) | 1.00 |
| Atezolizumab | 0 (0.0) | 2 (13.0) | 0.20 |
| Durvalumab | 1 (5.3) | 0 (0.0) | 1.00 |
| Avelumab | 1 (5.3) | 0 (0.0) | 1.00 |
| Myocarditis presentation | |||
| Chest pain | 7 (37.0) | 5 (31.0) | 1.00 |
| Shortness of breath | 11 (58.0) | 14 (88.0) | 0.07 |
| Orthopnea | 3 (16.0) | 7 (44.0) | 0.13 |
| Paroxysmal nocturnal dyspnea | 3 (16.0) | 3 (19.0) | 1.00 |
| Fatigue | 4 (21.0) | 6 (38.0) | 0.45 |
| Admission examination | |||
| Jugular venous distention | 7 (37.0) | 6 (38.0) | 1.00 |
| Crackles on lung examination | 10 (53.0) | 8 (50.0) | 1.00 |
| Admission vitals | |||
| Heart rate, beats/min | 87 ± 20 | 98 ± 27 | 0.21 |
| Systolic blood pressure, mm Hg | 130 ± 22 | 117 ± 25 | 0.14 |
| Diastolic blood pressure, mm Hg | 75 ± 10 | 66 ± 11 | 0.007 |
| Respiratory rate, rate/min | 23 ± 8 | 21 ± 5.6 | 0.69 |
| Oxygen requirement and delivery | |||
| Room air | 15 (79.0) | 6 (38.0) | 0.037 |
| Nasal cannula | 4 (21.0) | 4 (25.0) | |
| Intubated | 0 (0.0) | 4 (25.0) | |
| ECG, myocarditis admission | |||
| Sinus rhythm | 17 (90.0) | 10 (63.0) | 0.10 |
| QRS interval, ms | 102 ± 19 | 103 ± 20 | 0.83 |
| QTc interval, ms | 457 ± 28 | 457 ± 44 | 0.98 |
| Echocardiography, myocarditis admission | |||
| New LVEF, % | 49 ± 17 | 41 ± 18 | 0.25 |
| Change in LVEF from baseline | 16 ± 16 | 19 ± 11 | 0.66 |
| Left ventricular internal dimensions in diastole, mm | 49 ± 6 | 47 ± 14 | 0.41 |
| Pericardial effusion | 5 (26.0) | 1 (7.7) | 0.19 |
| Late gadolinium enhancement on a cardiac magnetic resonance study† | |||
| None | 6 (33.0) | 2 (15.0) | 0.41 |
| Subepicardial | 3 (16.0) | 3 (23.0) | 1.00 |
| Mid-myocardial | 4 (21.0) | 8 (62.0) | 0.06 |
| Diffuse | 5 (26.0) | 4 (31.0) | 1.00 |
| Elevated troponin | 17 (90.0) | 16 (100.0) | 0.48 |
| Troponin T, ng/ml‡ | |||
| Admission | 0.54 (0.01–1.55) | 1.18 (0.19–5.90) | 0.01 |
| Peak | 1.33 (0.01–3.5) | 2.68 (0.24–7.63) | 0.01 |
| Final/discharge | 0.14 (0.01–1.55) | 1.45 (0.03–6.41) | 0.002 |
| BNP or NT-proBNP | 12 (63.0) | 11 (69.0) | 1.00 |
| Serum sodium (admission), mEq/l | 137.0 ± 3.9 | 135.0 ± 4.1 | 0.144 |
| Serum creatinine (admission), mg/dl | 1.1 (0.5–2.6) | 1.1 (0.5–3.9) | 0.84 |
| White cell count (admission), cells/ml3 | 8.4 (4.4–14.5) | 11.6 (3.1–35.7) | 0.133 |
| Hemoglobin (admission), g/dl | 12.0 ± 1.9 | 12.8 ± 2.9 | 0.31 |
| Number of patient on steroids before myocarditis | 4 (21.0) | 3 (19.0) | 1.00 |
| Initial steroid dose, mg | 160.0 (0.0–1,000.0) | 72.5 (0.0–1,000.0) | 0.055 |
| Initial steroid dose/body weight, (mg/kg) | 2.06 (0.00–20.20) | 0.84 (0.00–14.40) | 0.041 |
| Time from admission to steroid administration, h | 18.3 ± 12.8 | 27.2 ± 17.5 | 0.12 |
Values are mean ± SD, n (%), or median (interquartile range).
*
If most recent ICI therapy was monotherapy.
†
Patients could have more than 1 pattern of late gadolinium enhancement; 18 of the patients without MACE and 13 of the patients with MACE had a cardiac magnetic resonance study.
‡
Admission troponin was the first measured serum troponin; peak troponin was the maximum measured troponin, and discharge/final troponin was defined as the troponin measured at discharge from index hospitalization or the troponin before an event if that event occurred on the index admission.
BNP = B-type natriuretic peptide; MACE = major adverse cardiac events; NT-proBNP = N-terminal pro–B-type natriuretic peptide; other abbreviations as in Table 1.