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Table 3 Comparison of Myocarditis cases with and without Flu vaccination (FV)

From: Influenza vaccination and myocarditis among patients receiving immune checkpoint inhibitors

  FV (n = 25) No FV (n = 76) P Value
Age at start of ICI, yrs 69 ± 8 66 ± 20 0.60
Male 17 (68) 56 (74) 0.58
CV risk factors
 Current or prior smoking 10 (48) 30 (47) 0.95
 Hypertension 14 (58) 45 (60) 0.89
 Diabetes mellitus 7 (30) 15 (21) 0.36
 No CV risk factors 4 (16) 19 (25) 0.35
Coronary artery disease 3 (15) 9 (13) 0.73
Stroke 1 (5) 6 (8) 1.00
Heart failure 1 (5) 4 (6) 1.00
COPD 5 (28) 7 (10) 0.12
Obstructive sleep apnea 0 6 (9) 0.60
Chronic kidney diseasea 2 (11) 7 (10) 1.00
Body mass index, kg/m2 28 ± 5 28 ± 7 0.90
Primary cancer type
 Head and neck 0 5 (7) 0.33
 Hodgkin’s lymphoma 0 2 (3) 1.00
 Melanoma 12 (48) 32 (42) 0.61
 Lung cancer 6 (24) 11 (14) 0.35
 Pancreatic 2 (8) 0 0.06
 Renal cell carcinoma 2 (8) 4 (5) 0.64
 Glioblastoma 0 2 (3) 1.00
 Other 3 (12) 20 (26) 0.18
Prior chemotherapy or radiation
 Radiation 4 (16) 25 (33) 0.11
 Anthracyclines 1 (4) 5 (7) 1.00
 Cyclophosphamide 1 (4) 1 (1) 0.44
 Gemcitabine 2 (8) 3 (4) 0.60
 Taxanes 2 (8) 4 (5) 0.64
 Carboplatin 2 (8) 6 (8) 1.00
 VEGF Inhibitors 0 1 (1) 1.00
Single agent vs. combined ICI
 Combination 8 (32) 20 (26) 0.61
 Monotherapy 17 (68) 56 (74) 0.61
Combined ICI
 Ipilimumab + nivolumab 8 (32) 16 (21) 0.27
 Ipilimumab + pembrolizumab 0 1 (1) 1.00
 Tremelimumab + avelumab 0 1 (1) 1.00
 Tremelimumab + durvalumab 0 2 (3) 1.00
Monotherapy ICI b
 Pembrolizumab (anti-PD1) 7 (28) 28 (37) 0.42
 Nivolumab (anti-PD1) 7 (28) 18 (24) 0.66
 Ipilimumab (anti-CTLA4) 2 (8) 4 (5) 0.64
 Tremelimumab (anti-CTLA4) 1 (4) 0 0.25
 Atezolizumab (anti-PDL1) 0 6 (8) 0.33
 Avelumab (anti-PDL1) 0 0 1.00
 Durvalumab (anti-PDL1) 0 0 1.00
Overall types of ICI
 Any anti-PD1 22 (88) 63 (83) 0.75
 Any anti-CTLA4 11 (44) 24 (32) 0.33
 Any anti-PDL1 0 9 (12) 0.11
Days of follow-up [IQR] 223 [111, 324] 162 [86, 364] 0.32
Other immune side effects during treatment c
 No other immune side effects 16 (64) 34 (45) 0.10
 Hypophysitis/pituitary/adrenal 1 (4) 5 (7) 1.00
 Pneumonitis 3 (12) 26 (36) 0.03
 Hepatitis 1 (4) 7 (9) 0.68
 Colitis 2 (8) 7 (9) 1.00
 Dermatitis 0 6 (8) 0.33
 Neurological 1 (4) 10 (13) 0.28
 Gastritis 0 (0) 3 (4) 0.57
Myocarditis presentation c
 Chest pain 15 (60) 50 (66) 0.60
 Shortness of breath 6 (25) 21 (28) 0.75
 Orthopnea 6 (26) 18 (24) 0.86
 Paroxysmal nocturnal dyspnea 2 (9) 7 (9) 1.00
 Fatigue 8 (40) 27 (46) 0.65
Admission examination
 Jugular venous distension 8 (32) 24 (32) 1.00
 Crackles on lung exam 8 (32) 36 (47) 0.25
Admission vitals
 Heart rate, beats/min 92 ± 16 89 ± 24 0.67
 Systolic blood pressure, mmHg 126 ± 17 126 ± 21 0.89
 Diastolic blood pressure, mmHg 70 ± 10 72 ± 11 0.48
 Respiratory rate, rate, min 19 ± 2 22 ± 14 0.38
Oxygen requirement and delivery d
 Room air 13 (72) 51 (75) 0.61
 Nasal cannula 5 (28) 13 (19) 0.61
 Intubated 0 4 (6) 0.61
Echocardiography, myocarditis admission
 LVEFe, % 46 ± 15 50 ± 16 0.28
 LVIDD, mm 45 ± 11 48 ± 6 0.15
Admission cardiac enzymes
 Troponin T, ng/ml 0.12 [0.02,0.47] 0.40 [0.11,1.26] 0.02
 BNP or NT-pro BNP, pg/ml 568 [421,987] 600 [215,4275] 0.82
Outcomes: MACE f
 Cumulative MACE 6 (24) 45 (59) 0.002
 Complete heart block 2 (9) 14 (19) 0.35
 Cardiogenic shock 2 (9) 15 (20) 0.35
Cardiac arrest 2 (9) 13 (17) 0.51
Cardiovascular death 4 (36) 28 (72) 0.04
  1. Values are mean ± SD or n (%), or median [interquartile range]. aChronic kidney disease = glomerular filtration rate < 60 ml/min/1.73 m2. bIf most recent ICI therapy was monotherapy. cCan include more than 1. dOf available cases (18 vaccinated, 69 unvaccinated).eAll vaccinated cases [25] and 74 of the 76 unvaccinated cases had an admission echocardiogram. fCases may have had more than one MACE, but only first event encountered was included in analysis. CV cardiovascular, ICI immune checkpoint inhibitors, anti-CTLA4 anti-cytotoxic T-lymphocyte-associated protein 4, anti-PD1 anti-programmed cell death protein 1, anti-PDL1 anti-programmed death-ligand 1, LVEF left ventricular ejection fraction, LVIDD left ventricular internal dimension diameter, BNP brain natriuretic peptide, NT- pro BNP N-terminal pro BNP