Skeletal Muscle Dysfunction in Adults with Congenital Heart Disease: Causes, Mechanisms and Rehabilitation

Background: The outstanding evolution in paediatric cardiac care have dramatically improved the prognosis for children with congenital heart disease. This has led to a continuous increase in the number of adults with congenital heart disease. In parallel with the improved longevity, the prevalence of long-term complications also increases.

Most patients have some degree of limitation in their physical capacity and where the skeletal muscles play a central role. As physical capacity is related both to symptoms and prognosis, improving muscle function may improve both general physical functioning and prognosis.

Aims: Our aims focus on skeletal muscle function and rehabilitation in the growing population of adults with congenital heart disease. These aims are to; A. Investigate factors associated with muscle dysfunction. B. Assess the impact of aging on muscle function. C. Clarify if the effect of conventional muscle exercise training is impaired.

D. Perform a randomised controlled muscle exercise training trial.

Work plan: The aims will be achieved by performing the following substudies, all in adults with congenital heart disease; 1. (Aim A) Skeletal muscle histopathology is assessed by immunohistochemistry on biopsies from m. vastus lateralis.

2. (Aim A) Skeletal muscle structure, volume, mass and fat content are investigated with peripheral quantitative computed tomography (pqCT).

3. (Aim A) The relation between maximal oxygen uptake and variables of skeletal muscle function (strength, endurance) are studied with cardio-pulmonary exercise tests, muscle function tests and assessment of skeletal muscle mass.

4. (Aim B) Study the relation between the frailty phenotype and skeletal muscle function and mass in patients > 40-years-of-age.

5. (Aim C) Clarify if the effect of skeletal muscle exercise training is blunted in adults with congenital heart disease. 6. (Aim D) Perform a controlled randomized skeletal muscle exercise training trial.

Significance: I consider this field of research as both new and understudied. The programme has its base in data from our previous studies and is an ongoing project. In short-term, this project establishes a new frontier of research in congenital heart disease. In long-term, rehabilitation targeting skeletal muscles can be introduced in the treatment of adults with congenital heart disease, based on translational studies, mechanistic studies and randomised, controlled trials.