Table 2.
Comparison of clinical presentation and outcomes in patients with and without late gadolinium enhancement
| With CMR (N = 103) | LGE present (N = 49) | LGE absent (N = 54) | Relative ratio or difference (95% CI)a | P-valueb | |
|---|---|---|---|---|---|
| Time from starting ICI to admission for myocarditis (days) | 64 (33–133) | 68 (32–97.5) | 74 (29–162) | NA | 0.44 |
| Myocarditis presentation | |||||
| Chest pain | 29 (28.2) | 14 (28.6) | 15 (27.8) | 1.0 (−0.2 to 0.2) | 0.93 |
| Shortness of breath | 57 (55.3) | 26 (53.1) | 31 (57.4) | 0.9 (0.7–1.3) | 0.66 |
| Orthopnoea | 22 (21.8) | 9 (19.2) | 13 (24.1) | 0.7 (0.3–1.4) | 0.31 |
| Paroxysmal nocturnal dyspnoea | 20 (19.6) | 8 (16.7) | 12 (22.2) | 0.6 (0.3–1.4) | 0.26 |
| Fatigue | 35 (38.0) | 13 (32.5) | 22 (42.3) | 0.8 (0.5–1.3) | 0.31 |
| Syncope | 9 (9.6) | 5 (11.9) | 4 (7.7) | 1.7 (0.8–3.8) | 0.20 |
| Sudden cardiac death | 1 (1.1) | 1 (2.4) | 0 (0) | 2.1 (0.7–6.6) | 0.20 |
| Palpitation | 26 (25.5) | 11 (22.9) | 15 (27.8) | 0.8 (0.4–1.5) | 0.47 |
| Physical exam | |||||
| Jugular vein distention | 30 (29.4) | 14 (29.2) | 16 (29.6) | 1.3 (0.8–2.2) | 0.28 |
| Crackles | 39 (38.6) | 18 (37.5) | 21 (39.6) | 1.1 (0.7–1.7) | 0.84 |
| Lower extremity oedema | 35 (34.3) | 16 (33.3) | 19 (35.2) | 1.2 (0.7–1.9) | 0.49 |
| SBP (mmHg) | 126.6 ± 20.2 | 124.7 ± 22.8 | 128.3 ± 17.6 | 3.6 (−4.9 to 12.0) | 0.40 |
| DBP (mmHg) | 72.9 ± 11.3 | 72.3 ± 12.8 | 73.5 ± 9.7 | 1.2 (−3.6 to 5.9) | 0.62 |
| Electrocardiogram at presentation | |||||
| Sinus rhythm | 82 (80.4) | 39 (79.6) | 43 (81.1) | 1.0 (0.8–1.2) | 0.85 |
| ST-segment or T-wave changes | 55 (54.5) | 25 (53.2) | 30 (55.6) | 1.0 (0.7–1.4) | 0.81 |
| Heart rate (beats/min) | 87.0 ± 22.4 | 87.8 ± 25.1 | 86.4 ± 20.5 | −1.4 (−11.5 to 8.6) | 0.78 |
| Biomarkers | |||||
| Initial troponin T (ng/mL) | 0.5 (0.1–1.7) | 1.0 (0.2–6.8) | 0.4 (0.1–1.1) | NA | 0.021 |
| Peak troponin T (ng/mL) | 1.0 (0.1–2.1) | 1.0 (0.2–4.5) | 0.9 (0.1–1.9) | NA | 0.22 |
| Initial BNP (pg/mL) (n = 84) | 589 (194–2413) | 838 (405–4592) | 478.5 (146.5–1350) | NA | 0.09 |
| Peak BNP (pg/mL) (n = 49) | 1088 (242–4873) | 1553.5 (734.5–6542.5) | 922 (194–2567) | NA | 0.16 |
| Echocardiogram | |||||
| Pre-ICI LVEF (%) (n = 66) | 61.1 ± 5.7 | 60.6 ± 5.4 | 61.6 ± 5.9 | 1.0 (−1.8 to 3.8) | 0.48 |
| Lowest LVEF at presentation (%) | 49.8 ± 16.6 | 47.7 ± 16.3 | 51.8 ± 16.8 | 4.2 (−2.3 to 10.7) | 0.20 |
| Change of LVEF (%) (n = 66) | 12.6±14.3 | 12.3 ± 12.9 | 12.9 ± 15.7 | 0.6 (−7.5 to 7.7) | 0.88 |
| LVEF<50% at presentation | 40 (38.8) | 22 (44.9) | 18 (33.3) | 0.8 (0.6–1.1) | 0.23 |
| LVIDD (mm) | 47.8 ± 6.1 | 48.3 ± 6.1 | 47.4 ± 6.1 | −0.8 (−3.6 to 1.9) | 0.53 |
| LVIDS (mm) | 35.0 ± 8.8 | 36.5 ± 8.7 | 33.5 ± 8.8 | −3.0 (−7.3 to 1.4) | 0.18 |
| LA size (mm) | 38.9 ± 7.6 | 39.9 ± 8.1 | 38.1 ± 7.3 | −1.8 (−5.8 to 2.2) | 0.38 |
| Pericardial effusion | 19 (23.5) | 8 (22.2) | 11 (24.4) | 0.9 (0.4–2.0) | 0.82 |
| Global longitudinal strain by echo (%) (n = 79) | −14.3 ± 2.9 | −13.8 ± 3.0 | −14.8 ± 2.8 | −1.1 (−2.4 to 0.2) | 0.099 |
| CMR | |||||
| 1.5 T | 81 (78.6) | 40 (81.6) | 41 (75.9) | 0.8 (0.4–1.6) | 0.48 |
| 3 T | 22 (21.4) | 9 (18.4) | 13 (24.1) | 0.8 (0.4–1.6) | 0.48 |
| LVEDV (mL) | 147.0 ± 39.7 | 149.1 ± 40.8 | 145.0 ± 38.9 | −4.0 (−19.8 to 11.7) | 0.61 |
| LV mass index (g/m2) | 72.4 ± 23.9 | 75.7 ± 26.8 | 69.3 ± 20.5 | −6.4 (−16.0 to 3.1) | 0.18 |
| LVEF by CMR (%) | 49.1 ± 15.1 | 47.5 ± 15.9 | 50.6 ± 14.4 | 3.1 (−2.8 to 9.0) | 0.30 |
| Oedema by T2-weighted STIR | 28 (27.5) | 18 (36.7) | 10 (18.9) | 2.0 (1.0–3.9) | 0.037 |
| Predominant LGE pattern | |||||
| Sub-endocardial/transmural | NA | 3 (6.1) | NA | NA | NA |
| Sub-epicardial | NA | 13 (26.5) | NA | NA | NA |
| Mid-myocardial | NA | 24 (49.0) | NA | NA | NA |
| Diffuse | NA | 9 (18.4) | NA | NA | NA |
| Native T1 value (ms) (n = 15) | 1167.2 ± 32.9 | 1174.3 ± 34.1 | 1162.4 ± 33.2 | −11.9 (−50.1 to 26.3) | 0.51 |
| Extracellular volume (%) (n = 8) | 34.3 ± 2.1 | 34.5 ± 1.9 | 34.0 ± 2.6 | −0.01 (−0.04 to 0.03) | 0.77 |
| Early gadolinium enhancement ratio (n = 15) | 2.8 ± 0.6 | 2.8 ± 0.6 | 2.9 ± 0.6 | 0.1 (−0.5 to 0.8) | 0.72 |
| Histopathology (n = 56) | |||||
| Fibrosis | 31 (55.4) | 11 (50.0) | 20 (58.8) | 0.9 (0.5–1.4) | 0.52 |
| Lymphocytes (T cell) | 55 (98.2) | 21 (95.5) | 34 (100.0) | 1.0 (0.9–1.1) | 0.21 |
| Histiocytes | 4 (7.1) | 1 (4.6) | 3 (8.8) | 0.5 (0.1–4.6) | 0.54 |
| Eosinophils | 4 (7.1) | 2 (9.1) | 2 (5.9) | 1.5 (0.2–10.2) | 0.65 |
| Outcomes | |||||
| Follow-up time for MACEc (days) | 148.5 (62–304) | 136 (63–259) | 162 (62–379) | NA | 0.33 |
| MACE (cumulative incidence)d | 41 (39.8) | 19 (38.8) | 22 (40.7) | 1.0 (0.6–1.5) | 0.84 |
| MACE (incidence rate, per person-year) | 0.63 | 0.68 | 0.59 | 1.2 (0.6–2.2) | 0.32 |
| Complete heart block (cumulative incidence) | 16 (15.8) | 7 (14.6) | 9 (17.0) | 0.9 (0.3–2.1) | 0.74 |
| Complete heart block (incidence rate, per person-year) | 0.25 | 0.26 | 0.25 | 1.0 (0.3–3.1) | 0.47 |
| Cardiogenic shock (cumulative incidence) | 15 (15.2) | 8 (17.0) | 7 (13.5) | 1.3 (0.5–3.2) | 0.62 |
| Cardiogenic shock (incidence rate, per person-year) | 0.24 | 0.29 | 0.20 | 1.5 (0.5–4.9) | 0.22 |
| Cardiac arrest (cumulative incidence) | 15 (15.2) | 7 (14.9) | 8 (15.4) | 0.9 (0.3–2.1) | 0.75 |
| Cardiac arrest (incidence rate, per person-year) | 0.27 | 0.26 | 0.28 | 0.9 (0.3–2.7) | 0.43 |
| CV death (cumulative incidence) | 17 (16.5) | 6 (12.2) | 11 (20.4) | 0.6 (0.2–1.5) | 0.27 |
| CV death (incidence rate, per person-year) | 0.26 | 0.22 | 0.30 | 0.7 (0.2–2.2) | 0.28 |
Values are mean ± SD, n (%), or median (interquartile range).
BNP, B-type natriuretic peptide; CMR, cardiovascular magnetic resonance; CV, cardiovascular; DBP, diastolic blood pressure; ICI, immune checkpoint inhibitors; LA, left atrium; LGE, late gadolinium enhancement; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; LVIDD, left ventricular internal diameter end diastole; LVIDS, left ventricular internal diameter end systole; LV mass, left ventricular mass; MACE, major adverse cardiovascular events; NA, not applicable; SBP, systolic blood pressure; SD, standard deviation; STIR, short tau inversion recovery.
Relative ratios and 95% CI for categorical variables and difference and 95% CI for normally distributed continuous variables. Cumulative incidence ratio (95% CI) and incidence rate ratio (95% CI) for MACE and individual MACE categories.
Comparison between patients with and without LGE using the Student’s t-tests or Wilcoxon Rank Sum tests for continuous variables, as appropriate based on their normality and the χ 2 test for categorical variables.
Time of the MACE was defined by the date of the earliest event when multiple MACE happened.
Patients may have multiple MACE.