Introduction
Steroid use has prolonged ambulation in Duchenne muscular dystrophy (DMD) and combined with advances in respiratory care overall management has improved such that cardiac manifestations have become the major cause of death. Unfortunately, there is no consensus for DMD-associated cardiac disease management.
Purpose
To assess effects of steroid use alone or in combination with angiotensin converting enzyme inhibitors (ACEI) or angiotension receptor blocker (ARB) on cardiac magnetic resonance imaging (CMR) derived circumferential strain (εcc).
Methods
We reviewed our DMD CMR database and medical records from February 2006 to 2010. The study cohort was divided into patients receiving steroids alone (Group A) or steroids plus ACEI or ARB (Group B). Analysis of covariance was used to assess the effect of medication on heart rate (HR), left ventricular ejection fraction (LVEF), mass (LVM), end diastolic volume (LVEDV) and εcc with age as a continuous covariate.
Results
A total of 206 studies from 136 DMD subjects were included in the analysis. Group A (114 studies) was younger than Group B (92 studies)(10±2.4 vs. 12.4±3.2 years, p< 0.0001). However, HR, LVEF, LVEDV and LVM were not different between the two groups (Table 1). εcc magnitude was significantly lower in Group B (-13.8±1.9 vs -12.8±2.0, p= 0.0004), but age correction using covariance analysis eliminated this effect (Table 2). After mean follow-up of 15 months, εcc of neither group improved compared with baseline (Table 3).
Table 1.
DMD Patients characteristics
| Parameter | Steroid Only (A) (n=114) | Steroid plus ACEI_ARB (B) (n=92) | P-value |
|---|---|---|---|
| Age (yrs) | 10.0 ± 2.4 | 12.4 ± 3.2 | <0.0001 |
| Heart Rate (bpm) | 101 ± 19 | 104 ± 15 | 0.2498 |
| LVEDV (mL) | 82.5 ± 21.8 | 86.7 ± 24.8 | 0.2023 |
| LVM (g) | 58.6 ± 19.4 | 62.1 ± 19.8 | 0.1031 |
| EF (%) | 64.2 ± 6.1 | 62.8 ± 7.5 | 0.1414 |
| εcc (%) | -13.8 ± 1.9 | -12.8 ± 2.0 | 0.0004 |
| Steroid dose (gram/kg/day) | 0.7 ± 0.29 | 0.6 ± 0.22 | 0.4838 |
| ACE-I dose (gram/kg/day) | N/A | 0.16 ± 0.08 | N/A |
| ARB dose (gram/kg/day) | N/A | 0.73 ± 0.29 | N/A |
Abbreviations: ACE-I = Angiotension Converting Enzyme Inhibitor, ARB = Angiotension Receptor Block, bpm = beat per minute, Clinic Prior to CMR = Previous Clinic Visiting Documenting Medication and Dose Prior to Cardiac Magnetic Resonance Imaging Study, DMD = Duchenne Muscular Dystrophy, εcc = Circumferential Strain, EF = Ejection Fraction, LVEDV = Left Ventricular Endiastolic Volume, LVM = Left Ventricular Mass.
Table 2.
Analysis of covariance summary results: Comparisons between steroid only vs. steroid plus ACEI_ARB (medication) adjusted for age as continuous variable.
| Medication | Age | |||
|---|---|---|---|---|
| Response Variable | F-statistics | P-value | F-statistics | P-value |
| Heart Rate (bpm) | 1.11 | 0.2930 | 0.00 | 0.9979 |
| LVEDV (mL) | 1.33 | 0.2503 | 37.01 | <0.0001 |
| LVM (g) | 2.19 | 0.1405 | 64.38 | <0.0001 |
| EF (%) | 0.03 | 0.8594 | 9.10 | 0.0029 |
| εcc (%) | 1.74 | 0.1885 | 30.85 | <0.0001 |
Abbreviations: ACE-I = Angiotension Converting Enzyme Inhibitor, ARB = Angiotension Receptor Block, bpm = beat per minute, εcc = Circumferential Strain, EF = Ejection Fraction, LVEDV = Left Ventricular Endiastolic Volume, LVM = Left Ventricular Mass.
Table 3.
DMD Serial Study Characteristics
| Group | Group A (Steroids) | Group B (Steroids plus) | Group A to B | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Number of patients | n=28 | n=31 | n=11 | ||||||
| Time Interval (mo) | Mean=14.9 ± 5.6; range = 8.5-29.7 | Mean = 15.1 ± 5.9; range 8.4-35.8 | Mean = 15.6 ± 5.9; range = 5.8-25.5 | ||||||
| CMR Study | Study 1 | Study 2 | P-value | Study 1 | Study 2 | P-value | Study 1 | Study 2 | P-value |
| Age (yrs) | 9.30 ± 1.5 | 10.5 ± 1.6 | <0.005 | 11.7 ± 3.4 | 12.97 ± 3.4 | 0.148 | 10.8 ± 2.5 | 12.0 ± 2.2 | 0.252 |
| HR (bpm) | 101 ± 21 | 99 ± 16 | 0.762 | 105 ± 14 | 105 ± 15 | 0.996 | 100 ± 14 | 102 ± 18 | 0.682 |
| LVEDV (mL) | 82.7 ± 19.3 | 86.5 ± 21.6 | 0.494 | 84.9 ± 29.2 | 90.0 ± 30.8 | 0.499 | 85.6 ± 18.6 | 81.2 ± 15.6 | 0.556 |
| LVM (g) | 57.1 ± 15.1 | 57.7 ± 16.9 | 0.890 | 60.9 ± 21.4 | 65.0 ± 21.4 | 0.478 | 61.3 ± 32.2 | 60.1 ± 14.0 | 0.909 |
| EF (%) | 64.6 ± 6.3 | 64.4 ± 5.8 | 0.906 | 64.9 ± 6.7 | 62.2 ± 9.1 | 0.194 | 61.2 ± 5.0 | 63.8 ± 5.8 | 0.261 |
| εcc (%) | -14.3 ± 1.6 | -13.7 ± 1.5 | 0.135 | -13.4 ± 1.7 | -12.1 ± 1.6 | 0.007 | -13.2 ± 1.8 | -11.9 ± 2.7 | 0.179 |
Conclusions
In a large consecutive database of DMD patients, serial CMR studies demonstrate that current and standard treatment strategy at our institution has little effect on DMD-associated cardiac disease. The failure of current regimens supports the need for rigorous prospective clinical trials to identify effective treatment regimens.