Introduction
Methods
Study group
Echocardiography
Invasive studies
Endomyocardial biopsy (EMB)
Laboratory measurements
Control group
Parameter | Healthy controls (n = 20) | Manufactures’ reference values |
---|---|---|
PICP (ng/ml) | 0.23 (0.06–0.32) | 0.064–0.186 |
PINP (pg/ml) | 129.9 (75.6–448.1) | 30.2–55.1 |
PIIICP (pg/ml) | 187.2 (88.1–390.3) | 5.2–35.5 |
PIIINP (ng/ml) | 3.32 (1.69–5.02) | 2.69–63.56 |
Col-1 (pg/ml) | 159.4 (31.2–512.9) | 46.7–178.9 |
TGF-β1 (ng/ml) | 2.22 (0.97–4.74) | 4.639–14.757 |
CTGF (ng/ml) | 2.37 (0.51–25.32) | 2.3–42.5 |
MMP-2 (ng/ml) | 4.43 (2.27–7.4) | Up to 400 |
MMP-9 (ng/ml) | 1.01 (0.29–3.59) | 2.0–139.4 |
TIMP-1 (ng/ml) | 2.61 (1.65–24.09) | Up to 400 |
Statistical analysis
Results
Patients characteristics
Parameter | Group 1 (n = 35) | Group 2 (n = 35) |
p value |
---|---|---|---|
Age (years) | 48.5 ± 12 | 47.5 ± 12.3 | 0.73 |
Sex (male/female) | 32 (91.4 %)/3 (8.6 %) | 31 (88.6 %)/4 (11.4 %) | 0.7 |
BMI (kg/m2) | 27.7 ± 5 | 26.7 ± 5.7 | 0.4 |
NYHA class | 2.49 ± 0.7 | 2.66 ± 0.76 | 0.33 |
Duration (months) | 2.34 ± 1.4 | 46.3 ± 39.7 | <0.001 |
LBBB (n, %) | 10 (28.6 %) | 8 (22.8 %) | 0.3 |
LVESd/BSA (mm/m2) | 28.3 ± 5.8 | 31.8 ± 7.9 | 0.04 |
LVEDd/BSA (mm/m2) | 34.2 ± 5.3 | 37.1 ± 8.2 | 0.08 |
LVESvol/BSA (ml/m2) | 91.9 ± 40.7 | 100.3 ± 56.2 | 0.48 |
LVEDvol/BSA (ml/m2) | 122.7 ± 55.2 | 130.7 ± 64.5 | 0.59 |
EF (%) | 24.5 ± 6.7 | 24.3 ± 8 | 0.91 |
E/E’ (average sep + lat) | 21.3 ± 12.6 | 20.5 ± 10.5 | 0.78 |
ECM fibrosis (n, %) | 7 (20 %) | 17 (48.6 %) | 0.01 |
PA mean (mmHg) | 22.6 ± 10.1 | 23.6 ± 11.7 | 0.69 |
pH (n, %) | 11 (33.3 %) | 16 (45.7 %) | 0.3 |
VO2peak (ml/kg/min) | 18.3 ± 6.5 | 15.5 ± 5.7 | 0.14 |
Hb (g/dl) | 14.54 ± 1.38 | 13.46 ± 1.74 | 0.006 |
CK-MB (U/l) | 11 (8–28) | 12 (8–29) | 0.08 |
hs-troponin T (ng/ml) | 0.0197 ± 0.0123 | 0.0251 ± 0.0223 | 0.2 |
hs-CRP (mg/dl) | 4.22 (0.15–141) | 1.89 (0.17–96) | 0.18 |
NT-proBNP (pg/ml) | 1505 (69–27,012) | 2088.5 (73–33,530) | 0.36 |
Beta-blocker (n, %) | 34 (97 %) | 35 (100 %) | 0.3 |
ACE-I (n, %) | 34 (97 %) | 32 (91.5 %) | 0.3 |
ARB (n, %) | 1 (3 %) | 1 (3 %) | 1 |
MRA (n, %) | 33 (94 %) | 33 (94 %) | 1 |
Furosemide (n, %) | 18 (51.4 %) | 24 (68.6 %) | 0.14 |
CRT/ICD (n, %) | 9 (25.7 %) | 18 (51.4 %) | 0.03 |
Comparison with controls
Parameter | DCM (n = 70) | Control (n = 20) |
p value |
---|---|---|---|
Age (years) | 48.04 ± 12.1 | 35.8 ± 7.9 | <0.001 |
LVEDd (mm) | 71.4 ± 11.5 | 49.3 ± 3.4 | <0.001 |
EF (%) | 24.4 ± 7.4 | 63.8 ± 4.7 | <0.001 |
PICP (ng/ml) | 0.17 (0.06–0.46) | 0.23 (0.06–0.32) | 0.56 |
PINP (pg/ml) | 129.9 (25.2–1050.2) | 129.9 (75.6–448.1) | 0.89 |
PIIICP (pg/ml) | 211.8 (70.3–1165.1) | 187.2 (88.1–390.3) | 0.47 |
PIIINP (ng/ml) | 4.41 (2.17–6.08) | 3.32 (1.69–5.02) | 0.001 |
Col-1 (pg/ml) | 57.7 (23.1–233.4) | 159.4 (31.2–512.9) | 0.001 |
TGF-β1 (ng/ml) | 2.26 (0.65–6.97) | 2.22 (0.97–4.74) | 0.81 |
CTGF (ng/ml) | 3.82 (0.48–23.87) | 2.37 (0.51–25.32) | 0.01 |
MMP-2 (ng/ml) | 6.06 (2.72–14.8) | 4.43 (2.27–7.4) | 0.001 |
MMP-9 (ng/ml) | 1.98 (0.28–9.25) | 1.01 (0.29–3.59) | 0.002 |
TIMP-1 (ng/ml) | 15.29 (1.8–36.17) | 2.61 (1.65–24.09) | 0.004 |
Comparison between early and chronic DCM
Parameter | Group 1 (n = 35) | Group 2 (n = 35) |
p value |
---|---|---|---|
PICP (ng/ml) | 0.18 (0.06–0.29) | 0.15 (0.06–0.46) | 0.52 |
PINP (pg/ml) | 132.1 (31.2–625.2) | 129.9 (25.2–1050.2) | 0.43 |
PIIICP (ng/ml) | 209.9 (77.2–1165.1) | 213.7 (70.3–717.7) | 0.79 |
PIIINP (ng/ml) | 4.3 (2.4–5.37) | 4.4 (2.17–6.08) | 0.51 |
Col-1 (pg/ml) | 67.44 (23.1–206.5) | 55.96 (31.2–233.4) | 0.42 |
TGF-β1 (pg/ml) | 2.21 (1.21–6.31) | 2.24 (0.65–6.9) | 0.86 |
CTGF (ng/ml) | 3.3 (0.48–12.4) | 4.99 (0.65–23.9) | 0.14 |
MMP-2 (ng/ml) | 5.99 (2.7–12.89) | 6.14 (2.97–14.83) | 0.58 |
MMP-9 (ng/ml) | 1.94 (0.28–9.25) | 1.99 (0.29–6.96) | 0.89 |
TIMP-1 (ng/ml) | 15.79 (1.8–35.16) | 14.88 (2.4–36.17) | 0.74 |
Comparison between fibrosis positive and negative DCM
Parameter | ECM fibrosis negative (n = 46, 65.7 %) | ECM fibrosis positive (n = 24, 34.3 %) |
p value |
---|---|---|---|
PICP (ng/ml) | 0.18 (0.06–0.46) | 0.16 (0.06–0.44) | 0.88 |
PINP (pg/ml) | 129.92 (25.2–625.2) | 128.75 (31.2–1050.2) | 0.7 |
PIIICP (ng/ml) | 241.1 (83.51–165.1) | 151.84 (70.3–717.7) | 0.12 |
PIIINP (ng/ml) | 4.41 (2.17–5.78) | 4.21 (2.9–6.08) | 0.94 |
Col-1 (pg/ml) | 56.89 (23.1–206.5) | 58.69 (27.9–233.4) | 0.96 |
TGF-β1 (pg/ml) | 2.18 (0.65–6.97) | 2.24 (1.21–5.89) | 0.32 |
CTGF (ng/ml) | 3.39 (0.48–12.4) | 4.3 (0.65–23.87) | 0.44 |
MMP-2 (ng/ml) | 6.06 (2.7–14.8) | 6.06 (2.97–8.43) | 0.99 |
MMP-9 (pg/ml) | 2.03 (0.28–9.25) | 1.59 (0.29–6.96) | 0.45 |
TIMP-1 (pg/ml) | 14.88 (1.8–35.16) | 15.31 (2.1–36.17) | 0.83 |
Parameter | Early DCM without fibrosis (n = 28) | Early DCM with fibrosis (n = 7) | Chronic DCM without fibrosis (n = 18) | Chronic DCM with fibrosis (n = 17) |
p value |
---|---|---|---|---|---|
PICP (ng/ml) | 0.19 (0.06–0.29) | 0.15 (0.06–0.28) | 0.15 (0.06–0.46) | 0.17 (0.08–0.44) | 0.89 |
PINP (pg/ml) | 138.7 (44.7–625.2) | 116.2 (31.2–221) | 128.8 (25.2–594.9) | 134.3 (48.1–1050.2) | 0.56 |
PIIICP (ng/ml) | 205.6 (83.5–1165) | 209.9 (77.2–648) | 258.5 (107.5–627.7) | 147.5 (70.3–717.7) | 0.49 |
PIIINP (ng/ml) | 4.4 (2.4–5.4) | 3.9 (3.1–5.01) | 4.42 (2.17–5.78) | 4.49 (2.92–6.08) | 0.75 |
Col-1 (pg/ml) | 72.3 (23.1–206.5) | 57.7 (27.9–107.6) | 47.8 (31.2–129.8) | 59.7 (31.2–233.4) | 0.48 |
TGF-β1 (ng/ml) | 2.2 (1.36–6.31) | 2.15 (1.2–5.88) | 1.85 (0.65–6.97) | 2.24 (1.49–5.73) | 0.66 |
CTGF (ng/ml) | 3.39 (0.48–12.4) | 2.92 (1.2–11.98) | 4 (1.44–11.75) | 5.15 (0.65–23.8) | 0.38 |
MMP-2 (ng/ml) | 5.99 (2.7–12.9) | 6.83 (4.56–7.24) | 6.21 (3.5–14.8) | 5.99 (2.97–8.43) | 0.83 |
MMP-9 (ng/ml) | 2.1 (0.28–9.24) | 1.34 (0.34–5.9) | 2.01 (0.58–5.77) | 1.72 (0.29–6.9) | 0.86 |
TIMP-1 (ng/ml) | 16.3 (1.8–35.2) | 15.3 (2.1–30.5) | 14.39 (2.4–29.8) | 15.9 (4.05–36.17) | 0.96 |
No correlations between serum fibrosis markers and ECM fibrosis
Probability of fibrosis
Parameter | Model 1 | Model 2 | Model 3 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
OR | 95 % CI |
p
| OR | 95 % CI |
p
| OR | 95 % CI |
p
| ||||
PICP (ng/ml) | 1.6 | 0.005 | >100 | 0.87 | 0.99 | 0.003 | >100 | 0.99 | 8.12 | 0.009 | >100 | 0.54 |
PINP (pg/ml) | 1.001 | 0.998 | 1.003 | 0.98 | 0.997 | 0.996 | 1.0031 | 0.88 | 0.999 | 0.996 | 1.003 | 0.72 |
PIIICP (ng/ml) | 0.999 | 0.996 | 1.001 | 0.302 | 0.999 | 0.996 | 1.001 | 0.348 | 0.999 | 0.996 | 1.002 | 0.38 |
PIIINP (ng/ml) | 1.001 | 0.999 | 1.005 | 0.9 | 0.998 | 0.999 | 1.004 | 0.76 | 0.998 | 0.999 | 1.0004 | 0.49 |
Col-1 (pg/ml) | 1.002 | 0.99 | 1.01 | 0.65 | 1.001 | 0.99 | 1.01 | 0.85 | 0.99 | 0.98 | 1.01 | 0.72 |
TGF1-beta (pg/ml) | 1.001 | 0.999 | 1.005 | 0.45 | 1.0024 | 0.9981 | 1.0068 | 0.27 | 1.0033 | 0.999 | 1.0081 | 0.17 |
CTGF (ng/ml) | 1.072 | 0.937 | 1.227 | 0.309 | 1.057 | 0.922 | 1.211 | 0.429 | 1.067 | 0.929 | 1.226 | 0.35 |
MMP-2 (ng/ml) | 0.925 | 0.731 | 1.171 | 0.517 | 0.878 | 0.684 | 1.128 | 0.309 | 0.861 | 0.663 | 1.119 | 0.26 |
MMP-9 (pg/ml) | 0.9991 | 0.999 | 1.0002 | 0.525 | 0.9998 | 0.9995 | 1.0002 | 0.454 | 0.9999 | 0.999 | 1.0002 | 0.5 |
TIMP-1 (pg/ml) | 1.0001 | 0.999 | 1.0006 | 0.67 | 1 | 0.9994 | 1.0005 | 0.922 | 0.9999 | 0.993 | 1.0005 | 0.7 |