Lack of Relationship between Fibrosis-Related Biomarkers and Cardiac Magnetic Resonance-Assessed Replacement and Interstitial Fibrosis in Dilated Cardiomyopathy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Cardiac Magnetic Resonance
2.2.1. Assessment of Replacement Fibrosis
2.2.2. Assessment of Interstitial Fibrosis
2.3. Laboratory Measurements
2.4. Statistical Analysis
3. Results
3.1. Baseline Characteristics
3.2. Comparisons of Biomarkers between DCM Patients, Stratified According to LGE and ECV
3.3. Associations between LGE and Biomarkers
3.4. Associations between ECV and Biomarkers
4. Discussion
4.1. Rationale of Circulating Markers of Fibrosis
4.2. Invasive vs. Non-Invasive Assessments of Cardiac Fibrosis
4.3. Relationship between Circulating Fibrosis-Related Molecules and EMB-Assessed Cardiac Fibrosis
4.4. Relationship between Circulating Fibrosis-Related Molecules and CMR-Assessed Cardiac Fibrosis
4.5. Relationship between Cardiac-Specific Biomarkers and Replacement and Interstitial Fibrosis
4.6. Study 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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Without LGE (n = 56) | With LGE (n = 44) | p-Value | ECV ≤ Median (n = 50) | ECV > Median (n = 50) | p-Value | |
---|---|---|---|---|---|---|
Age (year) | 44.86 ± 11.28 | 45.42 ± 12.29 | 0.76 | 41.87 ± 11.13 | 50.06 ± 11.06 | 0.0015 |
Male (n, %) | 49 (87.5%) | 38 (86.4%) | 0.87 | 40 (80%) | 45 (90%) | 0.13 |
BMI (kg/m2) | 28.21 ± 5.58 | 28.88 ± 5.97 | 0.54 | 29.08 ± 5.75 | 28.2 ± 6.13 | 0.50 |
HF symptoms time (month) | 18.69 ± 24.73 | 12.84 ± 21.7 | 0.32 | 13.75 ± 19.15 | 16.07 ± 27.26 | 0.41 |
Diabetes mellitus (n, %) | 7 (12.5%) | 7 (15.9%) | 0.63 | 7 (14%) | 8 (16%) | 0.76 |
Hypercholesterolemia (n, %) | 31 (55.4%) | 30 (68.2%) | 0.19 | 31 (62%) | 28 (56%) | 0.66 |
Hypertension (n, %) | 5 (8.9%) | 15 (34.1%) | 0.002 | 9 (18%) | 11 (22%) | 0.60 |
COPD (n, %) | 1 (1.8%) | 5 (11.4%) | 0.045 | 1 (2%) | 6 (12%) | 0.09 |
Atrial fibrillation (n, %) | 12 (21.4%) | 14 (31.8%) | 0.24 | 7 (14%) | 22 (44%) | 0.02 |
NYHA class | 1.73 ± 0.6 | 1.88 ± 0.63 | 0.26 | 1.72 ± 0.56 | 1.97 ± 0.65 | 0.10 |
SBP (mmHg) | 118.9 ± 17.3 | 121.8 ± 21.8 | 0.46 | 121.2 ± 16.8 | 118.6 ± 22.1 | 0.53 |
DBP (mmHg) | 75.16 ± 12.35 | 80.3 ± 14.25 | 0.03 | 76.68 ± 11.89 | 78.52 ± 14.24 | 0.51 |
Heart rate (bpm) | 70.54 ± 12.69 | 72.72 ± 14.71 | 0.74 | 69.81 ± 15.11 | 74.58 ± 12.98 | 0.12 |
QRS (ms) | 95.64 ± 24.17 | 106.14 ± 29.9 | 0.02 | 100.23 ± 28.07 | 102.05 ± 28.58 | 0.63 |
Ventricular arrhythmia (n, %) | 17 (31.5%) | 14 (32.6%) | 0.91 | 7 (14%) | 26 (52%) | <0.001 |
6MWT—distance (m) | 451.6 ± 90.4 | 438.7 ± 94.5 | 0.49 | 464.6 ± 89.2 | 416.1 ± 92.5 | 0.01 |
LVEDd/BSA (mm/m2) | 32.03 ± 4.51 | 30.99 ± 5.16 | 0.16 | 31.26 ± 4.35 | 31.85 ± 5.6 | 0.58 |
IVS (mm) | 9.65 ± 1.92 | 10.52 ± 2.47 | 0.05 | 9.66 ± 1.84 | 10.43 ± 2.58 | 0.11 |
LVEF (%) | 30.88 ± 10.14 | 28.06 ± 9.98 | 0.17 | 31.22 ± 9.89 | 27.47 ± 11.15 | 0.10 |
RVd (mm/m2) | 39.3 ± 6.4 | 39.34 ± 7.21 | 0.90 | 38.48 ± 6.58 | 40.52 ± 7.25 | 0.17 |
LAA (cm2) | 26.24 ± 6.79 | 29.98 ± 9.62 | 0.05 | 25.81 ± 8.2 | 30.98 ± 8.01 | <0.001 |
RAA (cm2) | 20.16 ± 6.79 | 21.69 ± 6.24 | 0.10 | 19.07 ± 5.26 | 23.4 ± 7.44 | 0.001 |
E/e’ | 9.17 ± 5.69 | 12.23 ± 5.77 | 0.003 | 9.96 ± 5.9 | 11.54 ± 6.33 | 0.25 |
MR ≥ moderate (n, %) | 17 (30.4%) | 17 (38.6%) | 0.39 | 9 (18%) | 27 (54%) | <0.001 |
TR ≥ moderate (n, %) | 7 (12.5%) | 4 (9.1%) | 0.59 | 2 (4%) | 9 (18%) | 0.04 |
TRV (m/s) | 2.58 ± 1.39 | 2.32 ± 1.23 | 0.37 | 2.32 ± 1.23 | 2.74 ± 1.44 | 0.14 |
LV mass (g) | 165.4 ± 44.2 | 203.5 ± 53.2 | <0.001 | 172.7 ± 48.3 | 193.2 ± 55.3 | 0.13 |
% LGE (%) | 0 | 4.55 ± 5.02 | <0.001 | 1.88 ± 1.59 | 5.85 ± 5.67 | 0.01 |
T1 native (ms) | 1207 ± 188 | 1285.2 ± 64.2 | 0.009 | 1255.5 ± 104.9 | 1274.7 ± 145.1 | <0.001 |
T1 post contrast (ms) | 470.7 ± 53.6 | 471.3 ± 44.1 | 0.95 | 485.3 ± 49.4 | 458.2 ± 42.4 | 0.007 |
ECV (%) | 28.0 ± 5.4 | 29.8 ± 4.2 | 0.01 | 25.3 ± 1.8 | 32.4 ± 4.5 | <0.001 |
Hct (%) | 42.26 ± 3.73 | 44.43 ± 5 | 0.01 | 43.49 ± 4.57 | 42.91 ± 4.6 | 0.55 |
WBC (M/uL) | 6.96 ± 2.05 | 8.52 ± 1.99 | <0.001 | 7.25 ± 2.09 | 8.1 ± 2.27 | 0.07 |
Creatinine (umol/L) | 90.34 ± 41.34 | 92.7 ± 21.83 | 0.13 | 92.91 ± 46.57 | 90.77 ± 21 | 0.64 |
Uric acid (umol/L) | 400.4 ± 112.2 | 450.4 ± 114.6 | 0.04 | 386.11 ± 102.29 | 455.51 ± 126.41 | 0.01 |
Cholesterol LDL (mmol/L) | 3.14 ± 0.95 | 3 ± 0.85 | 0.45 | 3.29 ± 0.94 | 2.82 ± 0.81 | 0.01 |
BB (n, %) | 56 (100%) | 44 (100%) | 1.00 | 50 (100%) | 50 (100%) | 1.00 |
ARNI/ACEi (n, %) | 56 (100%) | 43 (97.7%) | 0.26 | 50 (100%) | 49 (98%) | 0.31 |
MRA (n, %) | 55 (98.2%) | 41 (93.2%) | 0.20 | 48 (96.0%) | 48 (96.0%) | 1.00 |
Diuretic dosage (mg/day) | 35.12 ± 73.31 | 46.5 ± 42.48 | 0.03 | 28.95 ± 34.98 | 58.69 ± 82.12 | 0.01 |
Without LGE (n = 56) | With LGE (n = 44) | p-Value | ECV ≤ Median (n = 50) | ECV > Median (n = 50) | p-Value | |
---|---|---|---|---|---|---|
NT-proBNP (pg/mL) | 345 (109.5–1047) | 972 (432–1818) | <0.001 | 389 (81- 793.5) | 1371 (750–2652) | <0.001 |
hsTnT (ng/mL) | 0.007 (0.005–0.014) | 0.013 (0.009–0.02) | <0.001 | 0.009 (0.007–0.018) | 0.013 (0.007–0.02) | <0.001 |
CT-1 (pg/mL) | 42.3 (6.1–169.2) | 81.9 (4.9–225.1) | 0.81 | 60.3 (6.1–189) | 37.1 (4.9–225.1) | 0.69 |
PDGF-BB (pg/mL) | 254.7 (139.3–334.3) | 215.4 (135–362) | 0.36 | 221.6 (133–334) | 216.8 (139–331) | 0.95 |
GDF-15 (pg/mL) | 26.5 (18.3–47.1) | 28.3 (20.3–60.9) | 0.67 | 24.9 (18.1–40.8) | 33.7 (23.3–60.3) | 0.08 |
PICP (ng/mL) | 95.5 (65.7–173.4) | 75.8 (68.4–204) | 0.72 | 97.7 (71.7–306) | 77.1 (65.7–146) | 0.09 |
PIIINP (ng/L) | 161.2 (127.9–350.5) | 163.9 (135–445) | 0.79 | 165.5 (129–571) | 157 (127.9–309) | 0.26 |
CTIP (ng/mL) | 0.32 (0.22–0.38) | 0.28 (0.22–0.34) | 0.91 | 0.28 (0.21–0.35) | 0.29 (0.23–0.35) | 0.41 |
Univariate | Multivariate | |||
---|---|---|---|---|
OR (95%CI) | p-Value | OR (95%CI) | p-Value | |
QRS (ms) | 1.015 (0.999–1.031) | 0.06 | ||
LAA (cm2) | 1.058 (1.005–1.115) | 0.03 | 0.973 (0.91–1.04) | 0.42 |
Hb (g/dL) | 1.322 (1.003–1.742) | 0.04 | 1.112 (0.799–1.548) | 0.52 |
WBC (M/uL) | 1.451 (1.168–1.801) | <0.001 | 1.288 (0.997–1.664) | 0.05 |
Uric acid (umol/L) | 1.004 (0.999–1.008) | 0.05 | ||
hsTnT (ng/mL) | 3 × 1011 (6 × 10−3–4 × 1033) | 0.10 | ||
log10 (NT-proBNP) | 3.343 (1.619–6.901) | 0.001 | 2.979 (1.216–7.296) | 0.02 |
LV mass (g) | 1.016 (1.007–1.026) | <0.001 | 1.016 (1.004–1.029) | 0.009 |
loop diuretics (mg/d) | 1.003 (0.996–1.010) | 0.38 | ||
QRS (ms) | 1.015 (0.999–1.031) | 0.06 |
Univariate | Multivariate | |||
---|---|---|---|---|
Standard Coefficient | p-Value | Standard Coefficient | p-Value | |
Age (years) | 0.13 ± 0.04 | 0.002 | 0.03 ± 0.04 | 0.45 |
NYHA class | 2.37 ± 0.81 | 0.005 | 0.47 ± 0.87 | 0.59 |
Atrial fibrillation | −1.47 ± 0.56 | 0.01 | −1.09 ± 0.55 | 0.05 |
Ventricular arrhythmias | −1.57 ± 0.53 | 0.004 | −0.73 ± 0.53 | 0.17 |
COPD | −1.03 ± 1.03 | 0.32 | ||
IVS (mm) | 0.43 ± 0.23 | 0.07 | ||
LAA (cm2) | 0.09 ± 0.06 | 0.13 | ||
Uric acid (umol/L) | 0.011 ± 0.004 | 0.02 | 0.004 ± 0.004 | 0.31 |
Cholesterol LDL (mmol/L) | −1.56 ± 0.57 | 0.008 | −0.97 ± 0.63 | 0.13 |
hsTnT (ng/mL) | 11.92 ± 4.31 | 0.007 | 8.31 ± 3.70 | 0.03 |
log10 (NT-proBNP) | 3.04 ± 0.67 | <0.001 | 1.78 ± 0.80 | 0.03 |
hsCRP (mg/dL) | 0.09 ± 0.06 | 0.13 | ||
Loop diuretics (mg/day) | 0.02 ± 0.01 | 0.06 |
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Rubiś, P.; Dziewięcka, E.; Szymańska, M.; Banyś, R.; Urbańczyk-Zawadzka, M.; Krupiński, M.; Mielnik, M.; Wiśniowska-Śmiałek, S.; Karabinowska, A.; Podolec, P.; et al. Lack of Relationship between Fibrosis-Related Biomarkers and Cardiac Magnetic Resonance-Assessed Replacement and Interstitial Fibrosis in Dilated Cardiomyopathy. Cells 2021, 10, 1295. https://doi.org/10.3390/cells10061295
Rubiś P, Dziewięcka E, Szymańska M, Banyś R, Urbańczyk-Zawadzka M, Krupiński M, Mielnik M, Wiśniowska-Śmiałek S, Karabinowska A, Podolec P, et al. Lack of Relationship between Fibrosis-Related Biomarkers and Cardiac Magnetic Resonance-Assessed Replacement and Interstitial Fibrosis in Dilated Cardiomyopathy. Cells. 2021; 10(6):1295. https://doi.org/10.3390/cells10061295
Chicago/Turabian StyleRubiś, Paweł, Ewa Dziewięcka, Magdalena Szymańska, Robert Banyś, Małgorzata Urbańczyk-Zawadzka, Maciej Krupiński, Małgorzata Mielnik, Sylwia Wiśniowska-Śmiałek, Aleksandra Karabinowska, Piotr Podolec, and et al. 2021. "Lack of Relationship between Fibrosis-Related Biomarkers and Cardiac Magnetic Resonance-Assessed Replacement and Interstitial Fibrosis in Dilated Cardiomyopathy" Cells 10, no. 6: 1295. https://doi.org/10.3390/cells10061295
APA StyleRubiś, P., Dziewięcka, E., Szymańska, M., Banyś, R., Urbańczyk-Zawadzka, M., Krupiński, M., Mielnik, M., Wiśniowska-Śmiałek, S., Karabinowska, A., Podolec, P., Winiarczyk, M., Gliniak, M., Kaciczak, M., Robak, J., Karapetyan, A., & Wypasek, E. (2021). Lack of Relationship between Fibrosis-Related Biomarkers and Cardiac Magnetic Resonance-Assessed Replacement and Interstitial Fibrosis in Dilated Cardiomyopathy. Cells, 10(6), 1295. https://doi.org/10.3390/cells10061295