Table 5.

Echocardiographic parameters involved in chimeric antigen receptor T-Cell therapy-associated cardiac dysfunction.

	Echocardiographic Parameters Linked to Cardiac Dysfunction	Value (Baseline vs. Dysfunction)
Maude et al. (ELIANA), 2018 (n = 75; Pediatric) [31]	LVSF < 28% by echocardiogram LVEF < 45% by echocardiogram or MUGA	NR
Burstein et al., 2018 (n = 98; Pediatric) [27]	LVEF decrease of ≥10% or LVSF decrease of ≥5% compared with baseline or LVEF < 55% or LVSF < 28% in those with previously normal systolic function.	NR
Alvi et al., 2019 (n = 137; Adult) [21]	LVEF decrease > 10% to a value below 50%.	LVEF on the pre-CAR-T echocardiogram was 62 ± 7%, and the LVEDd was 46 ± 6 mm. Twenty nine patients had echocardiographic data pre- and post-CAR-T; of these, eight (28%) had a new reduction in LVEF. A decrease in LVEF from 60% to 19% and from 52% to 32% was described in two patients who died for cardiovascular causes.
Shalabi et al., 2020 (n = 52; Pediatric) [34]	LVEF > 10% absolute decrease compared to baseline or new-onset left ventricle systolic dysfunction (grade 2, LVEF < 50%). Severe cardiac dysfunction was defined by new-onset LV systolic dysfunction > grade 3 or LVEF < 40%) [23]. GLS was measured retrospectively from previously performed echocardiograms using specific strain software [24].	A total of 6% had an abnormal baseline EF. In contrast, baseline LV GLS was 16.8% (range: 14.1–23.5%, n = 37), with 78% (29/37) of patients having a reduced GLS pre-CAR-T-cell infusion (<19%). Six (12%) patients developed cardiac dysfunction (mean range 59% to 30%) including four patients with grade 3–4 CRS. They had concurrent abnormal myocardial strain, with a median LV GLS of 10.1% (range 5.3–14.1%). Four of the six patients had resolution of cardiac dysfunction by day 28 after CAR T-cell infusion. Two patients had persistent cardiac dysfunction with decreased LVEF at day 28 (they received the highest anthracycline exposure before starting CAR-T-cell infusion). One of these patients had the lowest LVEF (10%) during CRS and the other had a slight decrease in LVEF from baseline (50–40%); however, both patients recovered to baseline by the 3-month time point.
Ganatra et al.,2020 (n = 187, Adult) [20]	LVEF decrease >10% from baseline to <50% during the index hospitalization [25]. Other echo parameters analyzed were: LVEDd (mm); LVESd (mm); LA antero-posterior (mm); and their deviation from baseline.	A total of 12 patients developed new (n = 11) or worsening cardiomyopathy (n = 1), with a decrease in mean LVEF from 58% to 37% after a mean duration of 12.5 (range, 2–24) days from CAR T-cell infusion. LVEF improved in 9 of 12 patients over a median follow-up of 168.5 days, with normalization to ≥50% in 6 patients and partial recovery in 3 others. All 3 patients in whom LVEF did not recover died: 1 during the index hospitalization from refractory shock and 2 at 189 and 200 days after CAR-T-cell infusion.

CAR: chimeric antigen receptor; GLS: global longitudinal strain; IVS: interventricular septum; LA: left atrium; LVEF: left ventricle ejection fraction; LVEDd: left ventricle end-diastolic diameter; LVESd: left ventricle end-systolic diameter; LVSF: left ventricle shortening fraction; NR: not reported; MUGA: multigated acquisition scan; RVSP: right ventricle systolic pressure.