Cardiac Function and Serum Biomarkers throughout Staged Fontan Palliation: A Prospective Observational Study
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Study Cohort
3.2. Echocardiography
3.3. Serum Biomarkers
4. Discussion
Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Total Study Population (n = 60) | PCPC Group (n = 32) | TCPC Group (n = 28) | p | |
---|---|---|---|---|
Age (years) | 1.1 [0.6–2.6] | 0.6 [0.4–0.9] | 2.7 [2.2–3.8] | <0.001 |
Male sex | 35 (58%) | 19 (59%) | 16 (57%) | 0.861 |
BSA (m2) | 0.46 [0.36–0.57] | 0.36 [0.34–0.39] | 0.57 [0.53–0.64] | <0.001 |
Dominant ventricle | 0.956 | |||
LV | 22 (37%) | 12 (38%) | 10 (36%) | |
RV | 31 (52%) | 16 (50%) | 15 (54%) | |
Indeterminate | 7 (12%) | 4 (13%) | 3 (11%) | |
Cardiac diagnosis | 0.879 | |||
HLHS | 17 (28%) | 8 (25%) | 9 (32%) | |
TA | 10 (17%) | 6 (19%) | 4 (14%) | |
DORV | 8 (13%) | 4 (13%) | 4 (14%) | |
PA + IVS | 5 (8%) | 2 (6%) | 3 (11%) | |
Other | 20 (33%) | 12 (38%) | 8 (29%) | |
Extracardiac defects | 0.419 | |||
-Heterotaxy syndrome | 8 (13%) | 6 (19%) | 2 (7%) | |
-Other | 2 (3%) | 1 (3%) | 1 (4%) | |
Previous surgeries | 2 [1–3] | 1 [1–2] | 2 [2–3] | 0.001 |
Previous catheter interventions | 0 [0–1] | 0 [0–1] | 0 [0–1] | 0.267 |
mBT | n = 18 | n = 14 | ||
Pulmonary artery banding | n = 10 | n = 11 | ||
Norwood procedure | n = 11 | n = 9 | ||
Rashkind | n = 7 | n = 8 | ||
Central shunt | n = 2 | n = 2 | ||
Ductal stenting | n = 2 | n = 3 | ||
PCPC | n = 0 | n = 28 | ||
Other | n = 9 | n = 2 | ||
Intervention time (min) | 299 [261–356] | 293 [256–311] | 311 [281–348] | 0.475 |
Perfusion time (min) | 96 [64–115] | 83 [57–113] | 99 [90–119] | 0.121 |
Crossclamp time (min) | 47 [0–64] | 0 [0–58] | 59 [7–67] | 0.023 |
Total hospital stay (days) | 16 [10–27] | 11 [7–38] | 20 [14–25] | 0.061 |
Total ICU stay (days) | 2 [1–4] | 2 [1–4] | 2 [1–4] | 0.549 |
PCPC | TCPC | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
T1 | T2 | T3 | p T1 vs. T2 | p T2 vs. T3 | p T1 vs. T3 | T1 | T2 | T3 | p T1 vs. T2 | p T2 vs. T3 | p T1 vs. T3 | |
AV valve regurgitation | 7 | 5 | 2 | 0.190 | 0.713 | 0.162 | 5 | 4 | 3 | 0.441 | 0.551 | 0.927 |
(Neo)aortic regurgitation | 0 | 1 | 0 | - | - | - | 0 | 0 | 0 | - | - | - |
Systolic function | ||||||||||||
SV GLS | −15.1 ± 5.6 | −13.5 ± 5.2 * | −17.3 ± 4.5 | 0.047 | 0.016 | 0.357 | −16.9 ± 4.6 | −16.2 ± 3.8 * | −18.4 ± 3.0 | 0.246 | 0.106 | 0.218 |
SV lateral wall LS | −17.7 ± 5.8 | −14.5 ± 4.9 | −17.7 ± 5.0 | 0.032 | 0.105 | 0.946 | −17.2 ± 3.9 | −17.9 ± 4.2 | −20.0 ± 3.7 | 0.906 | 0.348 | 0.169 |
TDI lateral AV S’ (cm/s) | 6.6 ± 2.6 | 4.1 ± 1.4 ** | 5.1 ± 1.3 | 0.004 | 0.203 | 0.043 | 5.3 ± 1.6 | 5.3 ± 1.5 ** | 5.2 ± 1.1 | 0.617 | 0.301 | 0.434 |
AV-APSE (mm) | 9.5 ± 3.8 | 7.1 ± 1.8 ** | 8.7 ± 0.59 | 0.051 | 0.105 | 0.425 | 9.0 ± 1.9 | 9.4 ± 2.6 ** | 8.6 ± 2.6 | 0.578 | 0.189 | 0.451 |
Diastolic function | ||||||||||||
PW AV valve E (m/s) | 1.0 ± 0.3 ** | 0.8 ± 0.2 | 0.7 ± 0.1 | 0.061 | 0.837 | 0.231 | 0.7 ± 0.2 ** | 0.7 ± 0.2 | 0.7 ± 0.2 | 0.930 | 0.012 | 0.051 |
PW AV valve A (m/s) | 1.0 ± 0.4 ** | 0.7 ± 0.3 | 0.7 ± 0.2 | 0.018 | 0.469 | 0.089 | 0.7 ± 0.2 ** | 0.8 ± 0.2 | 0.6 ± 0.2 | 0.578 | 0.804 | 0.393 |
PW E/A ratio | 1.0 [0.92–1.4] | 1.0 [0.8–1.6] | 0.9 [0.9–1.0] | 0.109 | 0.109 | 0.999 | 1.0 [0.9–1.1] | 0.9 [0.7–1.2] | 0.9 [0.9–1.4] | 0.424 | 0.734 | 0.547 |
Deceleration time (ms) | 91 [84–103] | 92 [69–131] | 114 [96–129] | 0.999 | 0.999 | 0.039 | 110 [96–128] | 102 [79–109] | 94 [79–113] | 0.109 | 0.844 | 0.625 |
TDI lateral AV E’ (cm/s) | 9.9 ± 3.9 | 6.5 ± 2.9 | 7.8 ± 3.6 | 0.022 | 0.250 | 0.096 | 8.5 ± 3.5 | 8.0 ± 4.0 | 8.9 ± 2.8 | 0.386 | 0.690 | 0.510 |
TDI lateral AV A’ (cm/s) | 7.8 ± 3.3 | 5.1 ± 2.3 | 4.1 ± 1.4 ** | 0.010 | 0.803 | 0.024 | 6.1 ± 2.3 | 5.5 ± 1.7 | 6.7 ± 2.5 ** | 0.570 | 0.712 | 0.456 |
E/E’ | 8.9 [7.0–11.8] | 11.0 [10.4–13.4] | 9.3 [7.5–15.0] | 0.240 | 0.313 | 0.844 | 8.6 [7.1–10.5] | 9.0 [6.9–14.1] | 7.9 [5.4–8.6] | 0.569 | 0.129 | 0.688 |
Nt proBNP (pmol/L) | 102 [36–124] *** | 87 [62–153] | 26 [17–46] * | 0.901 | 0.002 | 0.002 | 23 [11–33] *** | 49 [26–126] | 15 [8–27] * | <0.001 | 0.003 | 0.495 |
Panel biomarkers principal component | ||||||||||||
PC1 | −0.3 ± 7.1 | −2.2 ± 5.1 | 0.4 ± 5.9 | 0.606 | 0.133 | 0.745 | 2.5 ± 5.6 | 0.6 ± 6.2 | −2.3 ± 3.4 | 0.174 | 0.460 | 0.017 |
PC2 | 2.0 ± 2.2 *** | 7.8 ± 1.6 * | −1.0 ± 0.8 ** | 0.368 | 0.045 | <0.001 | −1.7 ± 0.9 *** | 2.4 ± 2.8 * | −2.0 ± 1.0 ** | 0.004 | 0.003 | 0.529 |
PC3 | 2.4 ± 1.8 *** | −0.8 ± 0.1 * | −0.2 ± 1.8 | 0.636 | 0.245 | <0.001 | −0.0 ± 1.6 *** | −3.5 ± 2.9 * | −0.9 ± 2.1 | 0.011 | 0.020 | 0.222 |
PC4 | −0.6 ± 2.4 | −0.0 ± 0.2 * | −0.4 ± 1.7 | 0.434 | 0.349 | 0.840 | −0.5 ± 2.4 | 2.1 ± 1.6 * | 0.6 ± 2.3 | 0.079 | 0.237 | 0.013 |
PC 1 | PC 2 | PC 3 | PC 4 | |
---|---|---|---|---|
% of total variance explained | 37% | 8% | 7% | 5% |
Contributing biomarkers | Urokinase receptor | ITGB1 | PLC | JAM-A |
AXL | GDF-15 | MB | CASP 3 | |
ICAM2 | EGFR | COL1A1 | GP6 | |
ALCAM | OPN | PDGF subunit A | PECAM 1 | |
TNF receptor 1 | PON3 | PAI | SELP | |
Biological functions | Cell surface | Regulation of superoxide anion generation | Extracellular matrix organization | Positive regulation of platelet activation |
Integral component of plasma membrane | Blood vessel development | Cellular extravasation | ||
Circulatory system development | Leukocyte cell–cell adhesion | |||
Leukocyte migration |
Total Cohort | PCPC | TCPC | |||||||
---|---|---|---|---|---|---|---|---|---|
T2 | T1 and T3 | p | T2 | T1 and T3 | p | T2 | T1 and T3 | p | |
ITGB1 | 4.6 ± 0.4 | 5.2 ± 0.7 | 0.001 | 4.2 ± 0.1 | 5.1 ± 0.9 | <0.001 | 4.7 ± 0.4 | 5.4 ± 0.4 | 0.002 |
GDF-15 | 4.5 ± 0.8 | 3.9 ± 0.7 | 0.048 | 5.3 ± 1.2 | 3.9 ± 0.8 | 0.341 | 4.3 ± 0.6 | 3.8 ± 0.5 | 0.072 |
EGFR | 1.9 ± 0.4 | 2.3 ± 0.6 | 0.018 | 1.9 ± 0.4 | 2.2 ± 0.7 | 0.487 | 1.9 ± 0.4 | 2.4 ± 0.4 | 0.012 |
OPN | 9.7 ± 0.7 | 9.0 ± 0.9 | 0.040 | 10.3 ± 0.4 | 9.1 ± 1.1 | 0.063 | 9.5 ± 0.7 | 9.0 ± 0.5 | 0.133 |
PON3 | 3.9 ± 0.6 | 4.8 ± 0.9 | 0.001 | 4.2 ± 0.5 | 4.7 ± 1.0 | 0.420 | 3.8 ± 0.6 | 5.0 ± 0.7 | <0.001 |
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van der Ven, J.P.G.; Kamphuis, V.P.; van den Bosch, E.; Gnanam, D.; Terol, C.; Bogers, A.J.J.C.; Breur, J.M.P.J.; Berger, R.M.F.; Blom, N.A.; ten Harkel, A.D.J.; et al. Cardiac Function and Serum Biomarkers throughout Staged Fontan Palliation: A Prospective Observational Study. J. Cardiovasc. Dev. Dis. 2023, 10, 289. https://doi.org/10.3390/jcdd10070289
van der Ven JPG, Kamphuis VP, van den Bosch E, Gnanam D, Terol C, Bogers AJJC, Breur JMPJ, Berger RMF, Blom NA, ten Harkel ADJ, et al. Cardiac Function and Serum Biomarkers throughout Staged Fontan Palliation: A Prospective Observational Study. Journal of Cardiovascular Development and Disease. 2023; 10(7):289. https://doi.org/10.3390/jcdd10070289
Chicago/Turabian Stylevan der Ven, J. P. G., V P. Kamphuis, E van den Bosch, D Gnanam, C Terol, A J. J. C. Bogers, J. M. P. J. Breur, R. M. F. Berger, N. A. Blom, A. D. J. ten Harkel, and et al. 2023. "Cardiac Function and Serum Biomarkers throughout Staged Fontan Palliation: A Prospective Observational Study" Journal of Cardiovascular Development and Disease 10, no. 7: 289. https://doi.org/10.3390/jcdd10070289