Risk factors and diagnostic biomarkers for asymptomatic immune checkpoint inhibitor-related myocarditis in patients with esophageal cancer after immunotherapy

Table 1 Baseline characteristics of participants, mean ± SD/n (%)

Parameters	Non-occurrence group (n = 134)	Occurrence group (n = 68)	t/χ2 value	P value
Age (years)	62.36 ± 7.34	65.49 ± 8.96	2.654	0.009
Gender (male/female)	56 (41.79)/78 (58.21)	42 (61.76)/26 (38.24)	7.205	0.007
Body mass index (kg/m²)	21.36 ± 3.25	20.56 ± 3.44	1.622	0.106
Education level			0.782	0.676
Primary and below	24 (17.91)	9 (13.24)
Middle school	45 (33.58)	23 (33.82)
College and above	65 (48.51)	36 (52.94)
Marital status			0.640	0.726
Married	119 (88.81)	60 (88.24)
Divorced	11 (8.21)	7 (10.29)
Unmarried	4 (2.99)	1 (1.47)
Segmentation of lesions			3.179	0.365
Neck	42 (31.34)	16 (23.53)
Upper thoracic segment	35 (26.12)	25 (36.76)
Mid thoracic segment	36 (26.87)	19 (27.94)
Lower thoracic segment	21 (15.67)	8 (11.76)
Length of lesion			0.509	0.476
> 5 cm	78 (58.21)	36 (52.94)
≤ 5 cm	56 (41.79)	32 (47.06)
Tumor staging system staging			0.552	0.907
Phase I	12 (8.96)	6 (8.82)
Phase II	35 (26.12)	21 (30.88)
Phase III	41 (30.6)	20 (29.41)
Phase IV	46 (34.33)	21 (30.88)
Organizational classification			0.031	0.861
Squamous cell carcinoma	109 (81.34)	56 (82.35)
Adenocarcinoma	25 (18.66)	12 (17.65)
Hypertension	16 (11.94)	4 (5.88)	1.856	0.173
Diabetes	11 (8.21)	3 (4.41)	0.506	0.477
Coronary heart disease	14 (10.45)	4 (5.88)	1.158	0.282
ICI			5.195	0.023
ICI combination therapy	43 (32.09)	33 (48.53)
ICI monotherapy	91 (67.91)	35 (51.47)
Chemotherapy	52 (38.81)	26 (38.24)	0.006	0.937

ICI: Immune checkpoint inhibitor.

Table 2 Routine blood test, mean ± SD

Parameters	Non-occurrence group (n = 134)	Occurrence group (n = 68)	t value	P value
White blood cell (× 109/L)	4.65 ± 2.42	4.76 ± 2.35	0.307	0.759
Hemoglobin (g/L)	121.56 ± 22.34	127.06 ± 24.25	1.606	0.110
Platelet (× 109/L)	157.64 ± 55.27	149.46 ± 53.79	1.003	0.317
Neutrophil (× 109/L)	3.52 ± 1.96	3.49 ± 2.05	0.099	0.921
Lymphocyte (× 109/L)	1.52 ± 0.77	1.46 ± 0.48	0.711	0.478

Table 3 Cardiac biomarkers, mean ± SD

Parameters	Non-occurrence group (n = 134)	Occurrence group (n = 68)	t value	P value
Cardiac troponin I (ng/mL)	0.07 ± 0.03	0.07 ± 0.04	0.112	0.911
CK-MB (ng/mL)	3.05 ± 0.95	5.02 ± 1.49	25.032	< 0.001
CK (U/L	187.29 ± 58.25	212.25 ± 62.55	2.808	0.005
LDH (U/L)	210.35 ± 42.38	219.15 ± 41.94	1.400	0.163
Myoglobin (ng/mL)	60.58 ± 12.59	62.68 ± 13.96	1.082	0.280
NT-proBNP (pg/mL)	185.48 ± 36.89	194.13 ± 42.16	1.500	0.135

CK: Creatine kinase; LDH: Lactate dehydrogenase; NT-proBNP: N-terminal pro-B-type natriuretic peptide.

Table 4 Electrocardiogram, n (%)

Parameters	Non-occurrence group (n = 134)	Occurrence group (n = 68)	t value	P value
Premature atrial contractions	8 (5.97)	3 (4.41)	0.018	0.894
Premature ventricular contractions	5 (3.73)	2 (2.94)	0	1.000
Episodes of non-sustained supraventricular tachycardia	27 (17.91)	21 (30.88)	2.868	0.090
Episodes of non-sustained ventricular tachycardia	110 (82.09)	52 (69.12)	0.897	0.344
QRS duration			4.384	0.036
≥ 110 ms	24 (17.91)	21 (30.88)
< 110 ms	110 (82.09)	47 (69.12)

Table 5 Risk factor analysis

Parameters	Coefficient	SE	Wald	P value	OR	OR CI lower	OR CI upper
Age (years)	0.049	0.021	2.325	0.020	1.050	1.008	1.094
Gender (male/female)	0.787	0.343	2.290	0.022	2.196	1.120	4.305
ICI	0.485	0.350	1.386	0.166	1.624	0.818	3.223
CK-MB (μg/L)	0.133	0.053	2.499	0.012	1.142	1.029	1.267
CK (U/L)	0.024	0.009	2.681	0.007	1.025	1.007	1.043
QRS duration	0.707	0.388	1.820	0.069	2.028	0.947	4.342

OR: Odds ratio; CI: Confidence interval; CK: Creatine kinase; ICI: Immune checkpoint inhibitor.