ARTERIAL STIFFNESS IN PATIENTS WITH DUCHENNE MUSCULAR DYSTROPHY

Cardiomyopathy in Duchenne muscular dystrophy (DMD) is frequent and
characterized by progressive left ventricular (LV) fibrosis leading to
dysfunction and dilatation. Factors increasing LV afterload, such as aortic
stiffness, may promote LV wall stress and lead to worsening of LV function.

Little is known about the onset and course of arterial stiffness in DMD
patients over time, its relation with LV dysfunction and whether this is
influenced by treatment with an Angiotensin converting enzyme inhibitor (ACEi).
In DMD, ACEi are first-line treatment for cardiomyopathy as studies have shown
that early intervention with ACEi can favorably delay the onset and progression
of LV dysfunction. Whether these favorable results are a consequence of reduced
LV afterload is unknown. A meta-analysis in non-DMD patients showed that PWV is
reduced by treatment with ACEi, possibly independently of its ability to reduce
blood pressure.

Recently, Duchenne Care Considerations were published that propose the start of
ACEi at 10 years of age. This recommended age is largely based on expert
opinion and there is still debate about the optimal age for initiation of
treatment. A better understanding of the course of cardiovascular changes and
the influence of ACEi treatment could lead to refinement and a more
individualist ACEi treatment strategy for DMD patients.

We aim to investigate if aortic stiffness, measured by pulse wave velocity
(PWV), is present in patients with DMD and whether treatment with ACEi reduces
aortic stiffness.

This prospective observational study will be conducted at the LUMC.

The study has a cross sectional and longitudinal part.
• For the cross sectional part, patients will be included in the study during
their annual outpatient clinic visit. Only the PWV measurement will be
performed in research setting at this visit.
• The longitudinal part of this study will exist of patients that are starting
with ACEi therapy versus patients and their parents that choose not to start
(choice is independent of this protocol). Patients will be asked to join with
an additional informed consent form. The total duration for this part of the
study will be 1 year per patient. A detailed description about the procedures
of this study is stated in section 8 (protocol).

There are no risks associated with the measurements in this study. The PWV
measured by the Arteriograph is non-invasive and works like a regular blood
pressure measurement. DMD children are familiar with this measurements due to
their regular clinical care.
The entire study population will consist of children due to the manifestation
of (cardiomyopathy) in DMD at young age. The extent of burden is therefore low.

Subjects will not have direct personal benefit from participating in the study.
The data may however aid in detecting early manifestations of cardiomyopathy in
DMD. Identifying possible risk factors (i.e. arterial stiffness) for
accelerated progression may lead to new treatment strategies. These may include
an evidence based age for starting treatment with ACEi and, by identifying
possible non responders, a more personalized treatment strategy.