Background
Methods
Study design
Patients & setting
Ethics statement
Cardiac MRI
CMR image analysis
Biochemistry
Blood pressure
Electrocardiogram
Statistical analysis
Results
Patient | Age | Gender | Ethnicity | BMI | ALMS | Protein | ALMS | Protein | Infantile CM |
---|---|---|---|---|---|---|---|---|---|
mutation | change | mutation | change | ||||||
1 | 21 | Male | White British | 32.6 | c.6526C > T | p.Gln2176X | c.11101C > T | p.Arg3701X | Yes |
2 | 19 | Male | White British | 27.1 | c.6526C > T | p.Gln2176X | c.11101C > T | p.Arg3701X | No |
3 | 18 | Male | White British | 32.3 | c.8932C > T | p.GLN2978X | c.5356A > G | p.ASN1786Asp | Yes |
4 | 17 | Male | White British | 26.4 | c.10769delC | p.Thr3590LysfsX6 | c.5356A > G | p.Asn1786Asp | Yes |
5 | 20 | Male | White British | 31.5 | c6526C > T | p.Gln217X | c11101C > T | pArg3701X | No |
6 | 49 | Male | White British | 31.9 | c.10483C > T | p.Gln3495X | c.10775delC | P.Threo3592LysfsX6 | No |
7 | 40 | Male | White British | 38.4 | c.1729delA | p.Arg577Glyfsx17 | c.10477C > T | p.Gln3493X | No |
8 | 25 | Female | Mixed race | 30.0 | c.2218dupA | p.ThreoAsnfsX2 | c.1069C > T | p.Arg3657X | No |
9 | 45 | Male | White British | 35.3 | c.1874A > G | p.His623Arg | No | ||
10# | 44 | Male | White British | 28.2 | c.10769delC | p.Thr3590LysfsX6 | c.11410C > T | p.Arg38404X | Yes |
11 | 21 | Female | White British | 26.4 | c6584delA | p.Lys2195SerfX10 | C1008_1009delT | pCys336fsX1 | Yes |
12 | 22 | Female | White British | 27.6 | c.6823C > T | p.Arg2275X | c.9535C > T | P.Arg3179X | No |
13 | 26 | Male | White British | 22.7 | c.6823C > T | p.Arg2275X | c.9535C > T | P.Arg3179X | No |
14 | 29 | Male | White British | 31.6 | c.6895delG | p.val2299TrpsX43 | c.11443C > T | p.Gln3815X | No |
15 | 43 | Male | White British | 35.2 | c.8995C > T | p.Gln3493X | c>9001C > T | Gln3001 | No |
16 | 29 | Female | White British | 27.0 | c.8002C > T | p.arg2668X | c.10879C > T | pArg3627x | No |
17 | 18 | Male | BritishPakistani | 27.8 | c.4937C > A | p.Ser1646X | No | ||
18 | 20 | Male | BritishPakistani | 36.6 | c.7544-200_767 + 1110del | No | |||
19 | 19 | Male | BritishPakistani | 26.8 | c.7544-200_767 + 1110del | Yes | |||
20 | 21 | Female | BritishPakistani | 29.6 | c.5075delC | p.Pro1692LeufsX39 | c.5075delC | p.Pro1692LeufsX39 | Yes |
21 | 24 | Female | White British | 26.5 | Result awaited* | - | - | - | No |
22 | 20 | Male | BritishPakistani | 25.9 | c.4937C > A | p.Ser2646STOP | Yes | ||
23 | 19 | Female | British Indian | 19.4 | c.2041C > T | p.Arg681X | c.2041C > T | p.Arg681X | Yes |
24 | 23 | Male | British Indian | 28.9 | c.2041C > T | p.Arg681X | c.2041C > T | p.Arg681X | No |
25 | 32 | Female | White British | 25.7 | C11101C > T | p.R3701X | No | ||
26 | 20 | Female | White Australian | 37.7 | c.7911dupC | p.Asn2638Glnfs24 | No |
Controls | ALMS | |
---|---|---|
Number n
| 26 | 26 |
Age years | 27 ± 6 | 27 ± 9 |
Male n (%) | 17 (65 %) | 17 (65 %) |
Height (m) | 1.74 ± 0.09 | 1.61 ± 0.09** |
Weight (Kg) | 76 ± 16 | 77 ± 16 |
Body Mass Index | 25 ± 4 | 30 ± 5** |
Haemoglobin (g/dL) | 14.3 ± 1.2 | 14.0 ± 2.2 |
eGFR (ml/min/1.73 m2) | 87 ± 8 | 73 ± 25* |
Renin (pg/ml) a
| - | 41 (18–153) |
Aldosterone (pg/ml) a
| - | 97 (67–220) |
NT-pro BNP (ng/L) a
| 38 (4–75) | 37 (17–89) |
Cholesterol (mmol/L) | 4.6 (0.8) | 5.1 ± 1.3 |
Triglycerides (mmol/L) a
| 1.0 (0.6–1.4) | 2.5 (1.5–4.1)** |
High Density Lipoprotein (mmol/L) | 1.4 (0.3) | 0.9 ± 0.3** |
Glucose (mmol/L) a
| 4.7 (4.2–5.0) | 6.1 (4.6–15.0)* |
HbA1c (%) | - | 7.9 ± 2.7 |
Insulin (pmol/L) a
| - | 858 (239–1760) |
C-peptide:Glucose ratio (ng/ml:mg/dl) a
| - | 4.2 (2.2–6.2) |
ACR (mg/mmol) a
| 0.1 (0.05–0.2) | 1.5 (0.25–34) |
Urate (mmol/L) | 286 ± 67 | 409 ± 111* |
24 h daytime SBP (mmHg) | 119 ± 9 | 130 ± 14* |
24 h daytime DBP (mmHg) | 72 ± 7 | 77 ± 9* |
Cardiovascular structure, function & tissue characterization
Ventricular volumes and function
Controls | ALMS | ALMS | |||
---|---|---|---|---|---|
ECV < ULN | ECV > ULN | ECV > ULN | |||
NO LGE | LGE | ||||
Number n
| 26 | 26 | 12 | 5 | 9 |
Mean global ECV | 0.25 ± 0.01 | 0.30 ± 0.05* | 0.25 ± 0.02 | 0.31 ± 0.03a
| 0.34 ± 0.05b
|
Global pre contrast T1 (ms) | 970 ± 11 | 949 ± 35 | 934 ± 34 | 952 ± 33 | 972 ± 35 |
Global post contrast T1 (ms) | 522 ± 58 | 465 ± 61* | 472 ± 54 | 440 ± 47 | 437 ± 43 |
Diffuse LGE n
| 0 | 9 | 0 | 0 | 9 |
LVEDV (ml) | 133 ± 29 | 105 ± 23** | 107 ± 31 | 100 ± 13 | 108 ± 25 |
LVEDV index (ml/m2) | 69 ± 12 | 57 ± 11** | 57 ± 13 | 56 ± 11 | 58 ± 13 |
LVESV(ml) | 43 ± 13 | 38 ± 15 | 37 ± 15 | 32 ± 8 | 43 ± 19 |
LVESV index (ml/m2) | 22 ± 6 | 20 ± 8 | 20 ± 7 | 18 ± 5 | 23 ± 10 |
LVEF (%) | 68 ± 5 | 66 ± 8 | 67 ± 7 | 69 ± 5 | 62 ± 11 |
LV mass (g) | 115 ± 31 | 104 ± 27 | 106 ± 27 | 87 ± 13 | 112 ± 34 |
LV mass index (g/m2) | 60 ± 14 | 56 ± 12 | 56 ± 10 | 48 ± 8 | 60 ± 16 |
LV mass/ Height2.7 (g/m2.7) | 25 ± 6 | 29 ± 7* | 28 ± 6 | 24 ± 6 | 32 ± 9 |
LA volume (ml/m2) | 33 ± 8 | 35 ± 15 | 29 ± 8 | 40 ± 14 | 39 ± 15 |
MAPSE (mm) | 17 ± 2 | 12 ± 2* | 13 ± 2 | 13 ± 3 | 11 ± 3 |
Global long SS (%) | 14.7 ± 2.3 | 11.2 ± 2.6** | 12.9 ± 1.0 | 10.9 ± 2.0a
| 9.6 ± 1.9b
|
Global long SSR (s−1) | 0.83 ± 0.15 | 0.57 ± 0.11** | 0.63 ± 0.16 | 0.53 ± 0.11a
| 0.52. ± 0.15b
|
Global long ESR (s−1) | 0.62 ± 0.15 | 0.49 ± 0.18* | 0.54 ± 0.15 | 0.44 ± 0.19 | 0.41 ± 0.19 |