Background
Methods
Study population
Blood sampling in MD patients and controls
miRNA extraction and quantification
CMR data acquisition
CMR data analysis
Statistical analysis
Results
Patient characteristics
MD | Controls |
p value | |
---|---|---|---|
N = 63 |
N = 26 | ||
Male, n (%) | 63 (100) | 26 (100) | 1.00 |
Age, years | 31 ± 15 | 36 ± 13 | 0.09 |
BMI, kg/m2
| 24 ± 4 | 25 ± 3 | 0.36 |
Skeletal muscle status 0/1/2/3, n (%) | 2 (3)/43 (68)/13 (21)/5 (8) | 26 (100)/0 (0)/0 (0)/0 (0) |
<0.0001
|
Hypertension, n (%) | 3 (5) | 0 (0) | 0.55 |
Diabetes, n (%) | 0 (0) | 0 (0) | 1.00 |
ACE inhibitor, n (%) | 16 (25) | 0 (0) |
0.005
|
Beta-blocker, n (%) | 14 (22) | 0 (0) |
0.008
|
CK, U/L | 1226 (653–2424) | 120 (99–169) |
<0.0001
|
Elevated hs-Trop, n (%) | 30 (48) | 0 (0) |
<0.0001
|
Elevated NT-proBNP, n (%) | 3 (5) | 0 (0) | 0.55 |
Major CMR findings
MD | Controls |
p value | |
---|---|---|---|
N = 63 |
N = 26 | ||
LV-EDVi, ml/m2
| 85 ± 30 | 86 ± 16 | 0.80 |
LV-ESVi, ml/m2
| 41 ± 21 | 31 ± 9 |
0.003
|
LV-massi, g/m2
| 60 ± 16 | 58 ± 10 | 0.69 |
LV-EF, % | 53 ± 12 | 64 ± 6 |
<0.0001
|
RV-EF, % | 53 ± 9 | 55 ± 8 | 0.47 |
LV-EF <55 %, n (%) | 29 (46) | 0 (0) |
<0.0001
|
RV-EF <45 %, n (%) | 10 (16) | 0 (0) |
0.031
|
LGE presence, n (%) | 48 (76) | 0 (0) |
<0.0001
|
LGE extent, % | 7 (1-17) | - | - |
Abnormal CMR, n (%) | 49 (78) | 0 (0) |
<0.0001
|
miRNA findings in MD patients vs. controls
miRNA plasma levelsa (/103) | MD | Controls |
p value |
---|---|---|---|
N = 63 |
N = 26 | ||
-206 | 17.20 (4.29–63.96) | 0.19 (0.12–0.64) |
<0.0001
|
-144-5p | 9.85 (0.00–169.32) | 13.16 (6.53–19.63) | 0.81 |
-146b | 62.55 (0.00–176.97) | 16.64 (6.86–33.02) | 0.16 |
-15b | 0.00 (0.00–19.61) | 2.46 (0.81–3.93) | 0.64 |
-195 | 9.01 (0.52–21.73) | 13.63 (10.46–16.81) | 0.053 |
-20b | 61.74 (21.70–85.10) | 35.95 (27.39–51.02) |
0.048
|
-21 | 30.61 (0.00–110.97) | 9.58 (5.86–18.33) | 0.48 |
-221 | 0.00 (0.00–20.44) | 10.61 (7.73–17.12) |
0.001
|
-222 | 1923.17 (881.56–5111.93) | 79.22 (43.34–169.52) |
<0.0001
|
-26a | 293.34 (121.00–554.69) | 49.40 (26.58–63.10) |
<0.0001
|
-29a | 0.00 (0.00–0.00) | 0.07 (0.00–1.11) |
0.002
|
-29c | 0.00 (0.00–1.43) | 0.56 (0.27–2.72) |
0.001
|
-342 | 2427.02 (1198.59–4185.82) | 73.89 (45.30–171.19) |
<0.0001
|
-378a-3p | 30 (5.07–268.79) | 0.00 (0.00–0.23) |
<0.0001
|
-378a-5p | 27.57 (8.84–81.04) | 0.58 (0.30–1.79) |
<0.0001
|
-451 | 184.13 (73.28–343.07) | 144.45 (107.74–169.24) | 0.19 |
-93 | 26.82 (0.00–66.29) | 35.37 (25.60–49.70) | 0.24 |
Assessment of CMR and miRNA findings considering all CMR results
MD | Normal CMR | Abnormal CMR |
p value | |
---|---|---|---|---|
N = 63 |
N = 14 |
N = 49 | ||
Male, n (%) | 63 (100) | 14 (100) | 49 (100) | 1.00 |
Age, years | 31 ± 15 | 25 ± 18 | 32 ± 14 | 0.11 |
BMD, n (%) | 51 (81) | 13 (93) | 38 (78) | 0.27 |
BMI, kg/m2
| 24 ± 4 | 23 ± 6 | 24 ± 4 | 0.75 |
Skeletal muscle status 0/1/2/3, n (%) | 2 (3)/43 (68)/13 (21)/5 (8) | 2 (14)/10 (71)/1 (7)/1 (7) | 33 (67)/12 (25)/4 (8)/0 (0) | 0.07 |
ACE inhibitor, n (%) | 16 (25) | 1 (7) | 15 (31) | 0.09 |
Beta-blocker, n (%) | 14 (22) | 1 (7) | 13 (27) | 0.16 |
CK, U/L | 1226 (653-2424) | 764 (596-2411) | 1344 (783-2463) | 0.24 |
Elevated hs-Trop, n (%)a
| 30 (48) | 2 (14) | 28 (57) |
0.006
|
Elevated NT-proBNP, n (%)b
| 3 (5) | 0 (0) | 3 (6) | 1.00 |
MD | Normal CMR | Abnormal CMR |
p value | |
---|---|---|---|---|
N = 63 |
N = 14 |
N = 49 | ||
LV-EDVi, ml/m2
| 85 ± 30 | 72 ± 19 | 88 ± 32 | 0.08 |
LV-ESVi, ml/m2
| 41 ± 21 | 24 ± 7 | 46 ± 21 |
<0.0001
|
LV-mass, g/m2
| 60 ± 16 | 52 ± 11 | 62 ± 17 |
0.037
|
LV-EF, % | 53 ± 12 | 67 ± 6 | 50 ± 11 |
<0.0001
|
RV-EF, % | 53 ± 9 | 58 ± 7 | 52 ± 9 |
0.023
|
LV-EF <55 %, n (%) | 29 (46) | 0 (0) | 29 (59) | NA |
RV-EF <45 %, n (%) | 10 (16) | 0 (0) | 10 (20) | NA |
LGE presence, n (%) | 48 (76) | 0 (0) | 48 (98) | NA |
LGE extent, % | 7 (1–17) | - | 10 (4–24) | NA |
miRNA plasma levelsa (/103) | Normal CMR | Abnormal CMR |
p value |
---|---|---|---|
N = 14 |
N = 49 | ||
-206 | 14.36 (3.07–49.46) | 21.76 (4.82–72.71) | 0.68 |
-144-5p | 8.94 (0.00–163.41) | 9.85 (0.00–171.21) | 0.97 |
-146b | 84.15 (40.30–169.65) | 38.75 (0.00–177.31) | 0.25 |
-15b | 7.44 (0.00–21.87) | 0.00 (0.00–18.78) | 0.43 |
-195 | 9.76 (1.53–19.84) | 8.31 (0.57–21.25) | 0.86 |
-20b | 49.38 (29.88–79.03) | 65.38 (19.43–86.37) | 0.66 |
-21 | 71.91 (2.89–107.05) | 11.48 (0.00–113.69) | 0.61 |
-221 | 0.00 (0.00–35.26) | 0.00 (0.00–11.27) | 0.87 |
-222 | 1367.66 (689.45–1764.90) | 2230.30 (964.52–5884.91) | 0.09 |
-26a | 173.94 (47.45–324.42) | 326.81 (126.07–602.29) | 0.63 |
-29a | 0.00 (0.00–0.00) | 0.00 (0.00–0.00) | 0.94 |
-29c | 0.00 (0.00–2.24) | 0.00 (0.00–0.56) | 0.93 |
-342 | 1987.68 (808.31–2723.93) | 2639.34 (1333.85–5106.77) | 0.16 |
-378a-3p | 14.15 (0.00–273.74) | 39.74 (5.89–290.67) | 0.39 |
-378a-5p | 17.32 (2.66–40.41) | 39.29 (13.24–101.0) | 0.06 |
-451 | 104.66 (57.69–312.21) | 206.41 (110.79–338.52) | 0.27 |
-93 | 24.46 (0.38–55.52) | 26.95 (0.00–69.92) | 0.93 |
Assessment of CMR and miRNA findings according to “functional” CMR results
MD | Normal LV and RV function | Impaired LV and/or RV function |
p value | |
---|---|---|---|---|
N = 63 |
N = 31 |
N = 32 | ||
Male, n (%) | 63 (100) | 31 (100) | 32 (100) | 1.00 |
Age, years | 31 ± 15 | 27 ± 15 | 34 ± 15 | 0.11 |
BMD, n (%) | 51 (81) | 26 (84) | 25 (78) | 0.75 |
BMI, kg/m2
| 24 ± 4 | 24 ± 5 | 24 ± 3 | 0.72 |
Skeletal muscle status 0/1/2/3, n (%) | 2 (3)/43 (68)/13 (21)/5 (8) | 2 (7)/23 (74)/5 (16)/1 (3) | 20 (63)/8 (25)/4 (13)/0 (0) | 0.20 |
ACE inhibitor, n (%) | 16 (25) | 2 (7) | 14 (44) |
0.001
|
Beta-blocker, n (%) | 14 (22) | 4 (13) | 10 (31) | 0.13 |
CK, U/L | 1226 (653–2424) | 1250 (652–3043) | 1221 (727–2291) | 0.86 |
Elevated hs-Trop, n (%)a
| 30 (48) | 8 (26) | 22 (67) |
0.001
|
Elevated NT-proBNP, n (%)b
| 3 (5) | 0 (0) | 3 (9) | 0.24 |
MD | Normal LV and RV function | Impaired LV and/or RV function |
p value | |
---|---|---|---|---|
N = 63 |
N = 31 |
N = 32 | ||
LV-EDVi, ml/m2
| 85 ± 30 | 73 ± 18 | 96 ± 35 |
0.003
|
LV-ESVi, ml/m2
| 41 ± 21 | 27 ± 9 | 54 ± 21 |
<0.0001
|
LV-mass, g/m2
| 60 ± 16 | 53 ± 11 | 66 ± 18 |
0.001
|
LV-EF, % | 53 ± 12 | 63 ± 6 | 44 ± 9 | NA |
RV-EF, % | 53 ± 9 | 58 ± 7 | 49 ± 9 | NA |
LV-EF <55 %, n (%) | 29 (46) | 0 (0) | 29 (91) | NA |
RV-EF <45 %, n (%) | 10 (16) | 0 (0) | 10 (31) | NA |
LGE presence, n (%) | 48 (76) | 17 (55) | 31 (97) |
<0.0001
|
LGE extent, % | 7 (1–17) | 1 (0–6) | 16 (8–32) |
<0.0001
|
Abnormal CMR, n (%) | 49 (78) | 17 (55) | 32 (100) | NA |
miRNA plasma levelsa (/103) | Normal LV and RV function | Impaired LV and/or RV function |
p value |
---|---|---|---|
N = 31 |
N = 32 | ||
-206 | 31.77 (4.83–79.62) | 11.27(3.52–50.27) | 0.58 |
-144-5p | 33.14 (0.00–525.08) | 0.00 (0.00–98.72) | 0.29 |
-146b | 74.79 (0.00–173.85) | 29.92 (0.00–177.79) | 0.60 |
-15b | 0.00 (0.00–18.15) | 0.18 (0.00–21.81) | 0.77 |
-195 | 9.01 (0.35–18.62) | 8.93 (1.90–22.0) | 0.66 |
-20b | 53.99 (25.84–83.60) | 65.45 (19.35–87.12) | 0.66 |
-21 | 42.09 (0.00–102.71) | 13.65 (0.00–150.01) | 0.41 |
-221 | 0.00 (0.00–18.27) | 0.00 (0.00–18.55) | 0.36 |
-222 | 1801.09 (1215.81–3491.60) | 2006.29 (638.43–6059.36) | 0.79 |
-26a | 283.14 (110.62–512.14) | 362.31 (121.25–622.72) | 0.36 |
-29a | 0.00 (0.00–0.00) | 0.00 (0.00–0.05) | 0.39 |
-29c | 0.00 (0.00–0.47) | 0.00 (0.00–2.16) | 0.27 |
-342 | 2249.28 (1294.10–3353.27) | 2570.15 (888.62–5565.11) | 0.54 |
-378a-3p | 28.84 (6.04–155.98) | 32.92 (1.76–301.61) | 0.98 |
-378a-5p | 27.57 (12.50–56.49) | 26.02 (7.00–84.56) | 0.78 |
−451 | 184.13 (100.07–349.44) | 171.93 (22.68–307.38) | 0.77 |
−93 | 26.19 (0.00–70.81) | 27.17 (0.00–53.75) | 0.81 |
Assessment of CMR and miRNA findings according to “structural” CMR results
MD | LGE-negative | LGE-positive |
p value | |
---|---|---|---|---|
N = 63 |
N = 15 |
N = 48 | ||
Male, n (%) | 63 (100) | 15 (100) | 48 (100) | 1.00 |
Age, years | 31 ± 15 | 25 ± 17 | 32 ± 14 | 0.13 |
BMD, n (%) | 51 (81) | 14 (93) | 37 (77) | 0.26 |
BMI, kg/m2
| 24 ± 4 | 23 ± 5 | 24 ± 4 | 0.38 |
Skeletal muscle status 0/1/2/3, n (%) | 2 (3)/43 (68)/13 (21)/5 (8) | 2 (13)/11 (73)/1 (7)/1 (7) | 32 (67)/12 (25)/4 (8)/0 (0) | 0.06 |
ACE inhibitor, n (%) | 16 (25) | 1 (7) | 15 (31) | 0.09 |
Beta-blocker, n (%) | 14 (22) | 1 (7) | 13 (27) | 0.16 |
CK, U/L | 1226 (653–2424) | 773 (607–2187) | 1358 (797-2481) | 0.18 |
Elevated hs-trop, n (%)a
| 30 (48) | 2 (13) | 28 (58) |
0.003
|
Elevated NT-proBNP, n (%)b
| 3 (5) | 0 (0) | 3 (6) | 1.00 |
MD | LGE-negative | LGE-positive |
p value | |
---|---|---|---|---|
N = 63 |
N = 15 |
N = 48 | ||
LV-EDVi, ml/m2
| 85 ± 30 | 72 ± 18 | 89 ± 32 | 0.06 |
LV-ESVi, ml/m2
| 41 ± 21 | 25 ± 7 | 46 ± 22 |
<0.0001
|
LV-mass, g/m2
| 60 ± 16 | 51 ± 11 | 62 ± 17 |
0.018
|
LV-EF, % | 53 ± 12 | 66 ± 6 | 50 ± 11 |
<0.0001
|
RV-EF, % | 53 ± 9 | 56 ± 10 | 52 ± 9 | 0.15 |
LV-EF <55 %, n (%) | 29 (46) | 1 (7) | 28 (58) |
0.001
|
RV-EF <45 %, n (%) | 10 (16) | 1 (7) | 9 (19) | 0.43 |
LGE extent, % | 7 (1–17) | - | 10 (5–24) | NA |
Abnormal CMR, n (%) | 49 (78) | 1 (7) | 48 (100) | NA |
miRNA plasma levelsa (/103) | LGE-negative | LGE-positive |
p value |
---|---|---|---|
N = 15 |
N = 48 | ||
-206 | 13.18 (3.69–43.72) | 22.85 (4.56–74.83) | 0.54 |
-144-5p | 15.70 (0.00–159.39) | 4.93 (0.00–191.57) | 0.95 |
-146b | 81.86 (32.74–162.66) | 44.23 (0.00–177.79) | 0.32 |
-15b | 7.42 (0.00–21.10) | 0.00 (0.00–19.01) | 0.41 |
-195 | 10.50 (2.70–17.48) | 8.19 (0.54–21.93) | 0.75 |
-20b | 46.56 (31.69–74.64) | 65.45 (19.35–86.58) | 0.58 |
-21 | 67.48 (5.74–106.23) | 11.82 (0.00–115.78) | 0.65 |
-221 | 0.00 (0.00–32.92) | 0.00 (0.00–10.03) | 0.66 |
-222 | 1288.92 (355.69–1728.72) | 2303.59 (1102.54–6059.36) |
0.035
|
-26a | 165.39 (36.75–291.31) | 345.01 (139.78–616.20) |
0.030
|
-29a | 0.00 (0.00–.09) | 0.00 (0.00–0.00) | 0.61 |
-29c | 0.00 (0.00–2.14) | 0.00 (0.00–.65) | 0.89 |
-342 | 1906.24 (491.08–2603.63) | 2668.49 (1512.77–5205.06) | 0.07 |
-378a-3p | 13.18 (0.00–155.98) | 40.31 (8.05–301.61) | 0.26 |
-378a-5p | 16.99 (1.04–36.13) | 41.23 (14.62–102.03) |
0.026
|
-451 | 106.88 (64.56–273.40) | 207.05 (100.16–340.80) | 0.29 |
-93 | 23.85 (0.77–52.24) | 27.17 (0.00–70.37) | 0.89 |
Assessment of possible predictors of LGE presence
Variable (N = 63) | OR (95 % CI) |
p value |
---|---|---|
Age, years | 1.03 (0.99–1.08) | 0.13 |
BMD, n (%) | 4.16 (0.49–35.28) | 0.19 |
Skeletal muscle status 0/1/2/3, n (%) | 2.83 (0.84–9.50) | 0.09 |
Log10 CK, U/L | 1.69 (0.39–7.36) | 0.48 |
LV-EDVi, ml/m2
| 1.02 (0.99–1.05) | 0.06 |
LV-ESVi, ml/m2
| 1.11 (1.04–1.19) |
0.003
|
LV-mass, g/m2
| 1.06 (1.01–1.11) |
0.024
|
LV-EF, % | 0.81 (0.71–0.91) |
0.001
|
Elevated hs-Trop, n (%)a
| 9.1 (1.85–44.87) |
0.007
|
miR-222 (/103)c,d
| 2.51 (1.01–6.21) |
0.047
|
miR-378a-5p (/103)c,d
| 1.00 (0.99–1.01) | 0.86 |
miR-26a (/103)c
| 12.86 (1.07–154.34) |
0.044
|