Table 4.

Clinical characteristics, investigations, and treatments of 13 patients with grade ≥2 CV–irAEs.

Case no.	Age Sex	Stage	ECOG PS	Histological type	Type of ICIs	Pre-ICI LVEF, %	ECG Pre-ICI/during ICI	G 1 days to onset	G 1	Resolution of G 1	G ≥2 days to onset
1	80M	IV	0	Adeno	P	73	Normal/normal	565	BNP elevation	No	593
2	62M	IV	0	Sq	N	82	Normal/Af				583
3	71M	IV	0	Adeno	N	82	Normal/normal	141	BNP elevation	No	442
4	75F	IV	1	Sq	N	58	Normal/normal	128	BNP elevation	No	419/419
5	69M	III	0	Sq	N	70	Normal/Af	3	BNP elevation	No	246/321
6	79M	IV	0	Sq	P	59	Negative T-wave/Af				230/231
7	62M	IV	0	Sq	N	63	Normal/Af				175
8	71F	IV	0	Sq	N	57	Normal/negative T-wave				147
9	81M	III	0	Sq	P	83	Normal/normal	118	Troponin T conversion	No	139
10	79M	IV	3	Adeno	N	77	Negative T-wave/CAVB	59	BNP elevation	No	92
11	74M	IV	1	Adeno	N	78	Normal/Af				79
12	65M	III	0	Sq	A	77	Normal/Af				49
13	66M	IV	0	Adeno	P	75	Normal/Af				36

Case no.	G ≥2	Intervalsa, days	TnT during ICI treatmentb Pre-ICI/peak BNP level (pg/mL)	Advanced diagnostics: CAG/CMR/EMBx	Management	ICI discontinuationc
1	ADHF	28	TnT: negative BNP: 134/689	None	Diuretics Fluid restriction	No
2	Paf		TnT: negative BNP: 34/92	None	Follow-upd	No
3	ADHF	301	TnT: negative BNP: 90/880	None	Diuretics	No
4	ADHF/acute myocarditise	291	TnT: negative BNP: 123/490	CAG and EMBx	Diuretics β-blocker	Yes
5	Paf/VTe	243	TnT: negative BNP: 70/713	None	β-blocker	No
6	ADHF/Paf	168	TnT: negative BNP: 189/808	None	Diuretics	No
7	Paf		TnT: negative BNP: 12/129	None	Follow-upd	No
8	ADHF		TnT: negative BNP: 38/668	CAG and EMBx	Bed rest Fluid restriction	No
9	ADHF	21	TnT: positive BNP: 15/56	None	Diuretics	No
10	CAVBe	33	TnT: negative BNP: 54/249	CAG and EMBx	PMI	No
11	Paf		TnT: negative BNP: 4/124	None	Electrical cardioversion	No
12	Paf		TnT: negative BNP: 43/107	None	Pharmacological cardioversion	No
13	Paf		TnT: negative BNP: 25/ 99	None	β-blocker	No

Time intervals between the onset of the first grade 1 event and the first development of grade ≥2 event.

A cutoff of 0.1 ng/mL (TropT, Roche Diagnostics, Mannheim, Germany).

ICI treatment discontinuation exclusively due to cardiovascular immune-related adverse events.

The symptoms of atrial fibrillation were very mild, and therefore clinical follow-up was chosen without rate or rhythm control.

Grade 4 CV–irAE.

BNP elevation was defined as a BNP level below 200 pg/mL at baseline that subsequently increased to 200 pg/mL or more after ICI treatment initiation. Cardiac troponin T conversion was defined as a negative troponin T-test result at baseline that subsequently turned positive at least once after ICI treatment initiation.

Abbreviations: A: atezolizumab; Adeno: adenocarcinoma; ADHF: acute decompensated heart failure; Af: atrial fibrillation; BNP: B-type natriuretic peptide; CAG: coronary angiography; CAVB: complete atrioventricular block; CMR: cardiac magnetic resonance imaging; CV–irAEs: cardiovascular immune-related adverse events; ECG: electrocardiography; ECOG PS: Eastern Cooperative Oncology Group Performance Status Scale; EMBx: endomyocardial biopsy; G 1: grade 1 cardiovascular immune-related adverse events; G ≥2: grade ≥2 cardiovascular immune-related adverse events; ICI:immune checkpoint inhibitor; LVEF: left ventricular ejection fraction; N: nivolumab; P: pembrolizumab; Paf: paroxysmal atrial fibrillation; PMI: permanent pacemaker implantation; Sq: squamous cell carcinoma; TnT: troponin T; TTE: transthoracic echocardiography; VT: ventricular tachycardia.