Introduction
Materials and methods
Patient groups and CMR scheduling
CMR protocol
CMR data analysis
Myocardial strain analysis
Cancer therapy-related cardiac dysfunction
Statistical analysis
Results
Baseline demographics of both patient groups
Patients with epirubicin-based chemotherapy (n = 39) | Patients with left-sided radiotherapy (n = 27) | p value | |
---|---|---|---|
Demographics | |||
Age, yrs | 51 ± 11 | 56 ± 14 | 0.08 |
Weight, kg | 77 ± 15 | 69 ± 9 | 0.02 |
Height, m | 1.68 ± 0.07 | 1.68 ± 0.07 | 0.72 |
BMI, kg/m2 | 27 ± 5 | 25 ± 3 | 0.03 |
BSA, m2 | 1.86 ± 0.18 | 1.78 ± 0.13 | 0.04 |
Cancer stage | |||
DCIS, n (%) | 0 (0) | 4 (15) | 0.024 |
T1, n (%) | 8 (21) | 17 (63) | 0.028 |
T2, n (%) | 25 (64) | 6 (22) | 0.001 |
T3, n (%) | 2 (5) | 0 (0) | 0.51 |
T4, n (%) | 4 (10) | 0 (0) | 0.14 |
N0, n (%) | 18 (46) | 24 (89) | < 0.001 |
N1, n (%) | 21 (54) | 2 (7) | < 0.0001 |
N2, n (%) | 0 (0) | 1 (4) | 0.41 |
N3, n (%) | 0 (0) | 0 (0) | > 0.99 |
M0, n (%) | 39 (100) | 27 (100) | > 0.99 |
M1, n (%) | 0 (0) | 0 (0) | > 0.99 |
Cardiovascular risk factors | |||
Hypertension, n (%) | 6 (15) | 10 (37) | 0.08 |
Diabetes, n (%) | 0 (0) | 1 (4) | 0.41 |
Dyslipidemia, n (%) | 1 (3) | 2 (7) | 0.56 |
Current smoking, n (%) | 4 (10) | 1 (4) | 0.64 |
Family history of CAD, n (%) | 3 (8) | 2 (7) | > 0.99 |
Known CAD, n (%) | 1 (3) | 1 (4) | > 0.99 |
Cardiac medication | |||
Aspirin/clopidogrel, n (%) | 1 (3) | 3 (11) | 0.30 |
Statins, n (%) | 1 (3) | 2 (7) | 0.56 |
Beta-blockers, n (%) | 4 (10) | 3 (11) | > 0.99 |
ACEI or ARB, n (%) | 6 (15) | 6 (22) | 0.53 |
Laboratory tests | |||
HS TNT, pg/ml | 5 ± 4 | 5 ± 2 | 0.68 |
NT-proBNP, pg/ml | 121 ± 118 | 98 ± 85 | 0.40 |
Hematocrit, % | 37 ± 4 | 37 ± 3 | 0.96 |
Hb, mg/dl | 12.5 ± 1.1 | 12.7 ± 1.0 | 0.54 |
Creatinine, mg/dl | 0.82 ± 0.2 | 0.77 ± 0.12 | 0.20 |
Therapy-induced changes of laboratory and CMR parameters after chemotherapy
Baseline (n = 39) | FU1 (n = 39) | FU2 (n = 38) | p value for FU1 vs. FU2 | |
---|---|---|---|---|
Laboratory tests | ||||
HS TNT, pg/ml | 5 ± 4 | 8 ± 4* | 8 ± 11ll | 0.99 |
NT-proBNP, pg/ml | 121 ± 118 | 134 ± 274 | 142 ± 177 | 0.68 |
Hematocrit, % | 37 ± 4 | 35 ± 4‡ | 38 ± 3 | < 0.001 |
Hb, mg/dl | 12.5 ± 1.1 | 11.6 ± 1.2‡ | 12.6 ± 1.0 | < 0.001 |
Creatinine, mg/dl | 0.82 ± 0.2 | 0.76 ± 0.14 | 0.83 ± 0.12 | 0.01 |
Mapping parameters | ||||
T1, ms | 1244 ± 29 | 1293 ± 34‡ | 1250 ± 26 | < 0.001 |
T2, ms | 45 ± 3 | 48 ± 3‡ | 46 ± 3 | 0.007 |
Extracellular volume (%) | 28 ± 2 | 29 ± 2 | ||
Global LV strain | ||||
GLS, % | − 18 ± 2 | − 17 ± 2* | − 17 ± 2ll | 0.99 |
GCS, % | − 18 ± 2 | − 17 ± 3* | − 17 ± 3ll | 0.70 |
GRS, % | 36 ± 7 | 34 ± 8 | 34 ± 6 | 0.92 |
Left heart parameters | ||||
LVEF, % | 60 ± 5 | 60 ± 6 | 60 ± 6 | 0.51 |
LV mass index, g/m2 | 51 ± 5 | 51 ± 7 | 52 ± 7 | 0.49 |
LVEDVi, ml/m2 | 76 ± 10 | 72 ± 13† | 76 ± 12 | 0.003 |
LVESVi, ml/m2 | 30 ± 6 | 29 ± 7 | 31 ± 7 | 0.002 |
LVSVi, ml/m2 | 46 ± 7 | 43 ± 9* | 45 ± 8 | 0.09 |
LAESVi, ml/m2 | 34 ± 10 | 30 ± 9† | 34 ± 10 | < 0.001 |
LAEDVi, ml/m2 | 15 ± 6 | 14 ± 4 | 15 ± 6 | 0.09 |
Right heart parameters | ||||
RVEF, % | 56 ± 7 | 58 ± 8 | 58 ± 6 | 0.59 |
RVEDVi, ml/m2 | 77 ± 11 | 73 ± 14† | 74 ± 13 | 0.41 |
RVESVi, ml/m2 | 34 ± 8 | 31 ± 9† | 31 ± 6ll | 0.57 |
RVSVi, ml/ m2 | 43 ± 8 | 43 ± 9 | 43 ± 10 | 0.70 |
RAESVi, ml/m2 | 35 ± 9 | 30 ± 8‡ | 35 ± 10 | < 0.001 |
RAEDVi, ml/m2 | 20 ± 6 | 16 ± 5‡ | 17 ± 7¶ | 0.14 |
Presence of LGE, n (%) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
Therapy-induced changes of laboratory and CMR parameters after radiotherapy
Baseline (n = 27) | FU1 (n = 27) | FU2 (n = 27) | p value for FU1 vs. FU2 | |
---|---|---|---|---|
Laboratory tests | ||||
HS TNT, pg/ml | 5 ± 2 | 6 ± 3* | 5 ± 2 | 0.04 |
NT-proBNP, pg/ml | 98 ± 85 | 91 ± 73 | 107 ± 118 | 0.21 |
Hematocrit, % | 37 ± 3 | 38 ± 2 | 38 ± 2 | 0.62 |
Hb, mg/dl | 12.7 ± 1.0 | 12.9 ± 0.8 | 12.7 ± 0.8 | 0.63 |
Creatinine, mg/dl | 0.77 ± 0.12 | 0.77 ± 0.09 | 0.78 ± 0.11 | 0.56 |
Mapping | ||||
T1, ms | 1237 ± 29 | 1237 ± 42 | 1239 ± 39 | 0.80 |
T2, ms | 46 ± 3 | 47 ± 2 | 46 ± 3 | 0.30 |
Extracellular volume (%) | 30 ± 3 | 30 ± 3 | ||
Global LV strain | ||||
GLS, % | -18 ± 2 | -18 ± 2 | -18 ± 1 | 0.33 |
GCS, % | -18 ± 2 | -18 ± 2 | -19 ± 3 | 0.11 |
GRS, % | 39 ± 6 | 39 ± 9 | 39 ± 7 | 0.90 |
CMR – left heart | ||||
LVEF, % | 62 ± 5 | 64 ± 6 | 62 ± 5 | 0.19 |
LV mass index, g/m2 | 51 ± 5 | 52 ± 6 | 52 ± 6 | 0.59 |
LVEDVi, ml/m2 | 78 ± 10 | 75 ± 11* | 72 ± 11§ | 0.06 |
LVESVi, ml/m2 | 30 ± 6 | 29 ± 11 | 27 ± 6 | 0.34 |
LVSVi, ml/m2 | 48 ± 6 | 48 ± 10 | 45 ± 7‡ | 0.05 |
LAESVi, ml/m2 | 36 ± 10 | 34 ± 10 | 33 ± 10 | 0.54 |
LAEDVi, ml/m2 | 16 ± 7 | 15 ± 7 | 15 ± 6 | 0.89 |
CMR – right heart | ||||
RVEF, % | 57 ± 6 | 58 ± 7 | 60 ± 7 | 0.22 |
RVEDVi, ml/m2 | 81 ± 11 | 75 ± 14* | 75 ± 15‡ | 0.99 |
RVESVi, ml/m2 | 36 ± 7 | 32 ± 7† | 30 ± 8§ | 0.28 |
RVSVi, ml/ m2 | 45 ± 7 | 44 ± 10 | 45 ± 11 | 0.50 |
RAESVi, ml/m2 | 38 ± 12 | 37 ± 13 | 38 ± 15 | 0.61 |
RAEDVi, ml/m2 | 21 ± 7 | 19 ± 8 | 19 ± 11 | 0.94 |
LGE lesions, n (%) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
Patients with and without CTRCD
With CTRCD (n = 9) | Without CTRCD (n = 57) | |||||||
---|---|---|---|---|---|---|---|---|
Baseline | FU1 | FU2 | p | Baseline | FU1 | FU2 | p | |
HS Troponin T, pg/ml | 5 ± 3 | 8 ± 5 | 10 ± 16 | 0.60 | 5 ± 4 | 7 ± 4† | 6 ± 6 | 0.12 |
NTpro-BNP, pg/ml | 148 ± 159 | 225 ± 537 | 168 ± 254 | 0.60 | 102 ± 95 | 101 ± 107 | 121 ± 137 | 0.04 |
Hematocrit, % | 35 ± 4 | 34 ± 3 | 35 ± 4 | 0.34 | 38 ± 3 | 36 ± 4† | 38 ± 2 | < 0.001 |
Hb, mg/dl | 11 ± 1 | 11 ± 1 | 12 ± 1 | 0.19 | 13 ± 1 | 12 ± 1† | 13 ± 1 | 0.002 |
Creatinine, mg/dl | 0.87 ± 0.28 | 0.80 ± 0.14 | 0.86 ± 0.08 | 0.51 | 0.79 ± 0.16 | 0.76 ± 0.11 | 0.80 ± 0.12 | 0.04 |
T1, ms | 1246 ± 25 | 1299 ± 33‡ | 1246 ± 36 | < 0.001 | 1241 ± 29 | 1266 ± 47‡ | 1246 ± 32 | < 0.001 |
T2, ms | 46 ± 5 | 48 ± 2 | 46 ± 4 | 0.17 | 46 ± 3 | 47 ± 3‡ | 46 ± 3 | 0.02 |
ECV, % | 30 ± 2 | 29 ± 2 | 0.71 | 29 ± 3 | 29 ± 2 | 0.41 | ||
GLS, % | − 20 ± 1 | − 17 ± 3‡ | − 17 ± 1# | 0.91 | − 18 ± 2 | − 18 ± 2 | − 18 ± 2 | 0.29 |
GCS, % | − 19 ± 2 | − 16 ± 3† | − 16 ± 3¶ | 0.92 | − 18 ± 2 | − 18 ± 2 | − 18 ± 3 | 0.33 |
GRS, % | 40 ± 7 | 31 ± 9† | 32 ± 5¶ | 0.63 | 37 ± 7 | 37 ± 8 | 37 ± 7 | 0.90 |
LVEF, % | 61 ± 3 | 58 ± 6 | 55 ± 4ll | 0.20 | 61 ± 5 | 62 ± 6 | 62 ± 6 | 0.34 |
LV mass index, g/m2 | 50 ± 6 | 54 ± 9 | 54 ± 8 | 0.95 | 51 ± 5 | 51 ± 6 | 51 ± 6 | 0.73 |
LVEDVi, ml/m2 | 79 ± 9 | 73 ± 11 | 80 ± 13 | 0.09 | 76 ± 10 | 73 ± 12‡ | 74 ± 11ll | 0.31 |
LVESVi, ml/m2 | 31 ± 3 | 31 ± 7 | 36 ± 6ll | 0.03 | 30 ± 6 | 27 ± 7† | 28 ± 7 | 0.12 |
LVSVi, ml/m2 | 48 ± 7 | 43 ± 8 | 45 ± 8 | 0.49 | 47 ± 7 | 45 ± 9 | 45 ± 7 | 0.84 |
LAESVi, ml/m2 | 36 ± 12 | 29 ± 6 | 32 ± 9 | 0.45 | 35 ± 10 | 32 ± 10 | 34 ± 10 | 0.10 |
LAEDVi, ml/m2 | 15 ± 7 | 14 ± 3 | 15 ± 4 | 0.77 | 15 ± 6 | 15 ± 6 | 15 ± 6 | 0.22 |
RVEF, % | 57 ± 8 | 54 ± 12 | 57 ± 6 | 0.43 | 56 ± 7 | 59 ± 7* | 59 ± 7ll | 0.95 |
RVEDVi, ml/m2 | 78 ± 12 | 68 ± 15† | 72 ± 10 | 0.22 | 79 ± 11 | 75 ± 14† | 75 ± 15ll | 0.85 |
RVESVi, ml/m2 | 34 ± 10 | 32 ± 13 | 30 ± 5 | 0.61 | 35 ± 7 | 31 ± 7‡ | 31 ± 7# | 0.99 |
RVSVi, ml/ m2 | 44 ± 7 | 36 ± 8* | 41 ± 8 | 0.11 | 44 ± 8 | 44 ± 9 | 44 ± 11 | 0.82 |
RAESVi, ml/m2 | 32 ± 7 | 28 ± 6 | 32 ± 8 | 0.07 | 37 ± 11 | 34 ± 12* | 37 ± 13 | 0.02 |
RAEDVi, ml/m2 | 19 ± 6 | 15 ± 4* | 17 ± 7 | 0.25 | 21 ± 7 | 18 ± 7† | 18 ± 9ll | 0.50 |
Diagnostic accuracy of parameters at FU1 to predict later CTRCD at FU2
p vs T1 | CTRCD (n = 9) | No CTRCD (n = 57) | Total | Sensitivity | Specificity | Accuracy | PPV | NPV | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Parameter | AUC (95% CI) | Cutoff | TP | FN | FP | TN | (n = 66) | (%) | (%) | (%) | (%) | (%) | ||||||
T1 | 0.712 (0.587–0.816) | –- | > 1262 ms | 9 | 0 | 32 | 25 | 66 | 100 (66–100) | 44 (31–58) | 52 (40–63) | 22 (12–37) | 100 (84–100) | |||||
GCS | 0.712 (0.585–0.818) | 0.951 | > -17% | 6 | 3 | 14 | 41 | 64 | 67 (30–93) | 75 (61–85) | 73 (61–83) | 30 (14–52) | 93 (81–98) | |||||
LVEF | 0.706 (0.581–0.811) | 0.956 | ≤ 60% | 7 | 2 | 18 | 39 | 66 | 78 (40–97) | 68 (55–80) | 70 (58–80) | 28 (14–48) | 95 (83–100) | |||||
GRS | 0.671(0.542–0.783) | 0.651 | ≤ 39% | 9 | 0 | 35 | 20 | 64 | 100 (66–100) | 36 (24–50) | 45 (34–57) | 20 (11–35) | 100 (81–100) | |||||
GLS | 0.636 (0.507–0.753) | 0.518 | > -16% | 4 | 5 | 7 | 48 | 64 | 44 (14–79) | 87 (76–95) | 81 (70–89) | 36 (15–65) | 91 (79–96) | |||||
NT-proBNP | 0.625 (0.496–0.742) | 0.558 | ≤ 41 ng/l | 6 | 3 | 14 | 42 | 65 | 67 (35–88) | 75 (62–85) | 74 (62–83) | 30 (14–52) | 93 (81–98) | |||||
HS TNT | 0.527 (0.399–0.652) | 0.064 | > 5 pg/ml | 6 | 3 | 30 | 25 | 65 | 67 (35–88) | 46 (34–59) | 49 (37–61) | 17 (7–32) | 90 (73–97) | |||||
T2 | 0.513 (0.386–0.638) | 0.120 | > 45 ms | 9 | 0 | 44 | 13 | 66 | 100 (66–100) | 23 (13–36) | 33 (23–45) | 17 (9–29) | 100 (73–100) | |||||
Combined parameter | ||||||||||||||||||
T1 + LVEF | 0.810 (0.695–0.896) | 0.298 | > 1262 ms/ ≤ 60% | 7 | 2 | 9 | 48 | 66 | 78 (44–95) | 84 (72–92) | 83 (72–91) | 44 (23–67) | 96 (86/100) | |||||
T1 + GRS | 0.800 (0.681–0.890) | 0.258 | > 1262 ms/ ≤ 39% | 9 | 0 | 22 | 33 | 64 | 100 (66–100) | 60 (47–72) | 66 (53–76) | 29 (13–47) | 100 (88–100) | |||||
T1 + GCS | 0.762 (0.640–0.859) | 0.639 | > 1262 ms/ > -17% | 6 | 3 | 8 | 48 | 65 | 67 (35–88) | 86 (74–93) | 83 (72–90) | 43 (21–67) | 94 (83–99) | |||||
T1 + GLS | 0.686 (0.558–0.796) | 0.752 | > 1262 ms/ > 16% | 4 | 5 | 4 | 51 | 64 | 44 (19–73) | 93 (82–98) | 86 (75–93) | 50 (22–78) | 91 (80/97) | |||||
T1 + NT-proBNP | 0.690 (0.564–0.798) | 0.766 | > 1262 ms/ ≤ 41 pg/ml | 5 | 4 | 10 | 46 | 65 | 56 (27–81) | 82 (70–90) | 78 (67–87) | 33 (15–59) | 92 (81/97) |