Chronic heart failure develops mostly slowly in humans, which leads to a slow transition of adaptive hypertrophy to maladaptive decompensation. This also affects peripheral organs in patients. As a consequence, exercise intolerance is a cardinal symptom in right ventricular (RV) and left ventricular (LV) failure. The underlying skeletal muscles contribute to an increased morbidity in diseased patients. So far, differences in the development of left and right heart failure and their effects on peripheral organs are insufficiently understood. In this study we aimed to generate a novel two-stage model of RV failure and compare RV failure in this model to an established model of LV failure, as well as the effects on skeletal muscle sarcopenia. Therefore, pulmonary artery banding (PAB) or aortic banding (AOB) were performed in weanling rats, with a non-constricting clip at the time of surgery inducing a slow transition from compensated cardiac hypertrophy (7 weeks after banding) to heart failure (22-26 weeks after banding). Subsequently, cardiac function was characterized by echocardiography. Plasma parameters were analysed by the use of ELISA assays and the differential effects of RV and LV failure onto the skeletal muscles were investigated. Metabolic balance and energy metabolism were analysed within three different skeletal muscles, soleus and gastrocnemius muscle as well as the diaphragm, were analysed by histological staining, mitochondrial function analysis (enzymatic activity and oxygen consumption), real-time qPCR and western blot. Echocardiographic analyses and blood parameters (BNP) revealed two clearly distinguishable stages of left and right heart disease with a comparable severity. Compensatory hypertrophy results only in minor changes, at the stage of decompensation instead soleus and gastrocnemius muscle of AOB rats demonstrated a significant impairment. They showed a reduced weight as well as a reduced fibre diameter, higher proteasome activity and expression of the muscle-specific ubiquitin E3 ligase “muscle-specific RING finger 1“. Furthermore, an increased expression of the atrophy marker myostatin, increased autophagy activation, impaired mitochondrial function, and impaired respiratory chain gene expression could be observed. In PAB animals soleus and gastrocnemius muscle did not show these significant changes, only minor effects could be observed. The diaphragm did not show any differences in both models and disease stages except the myostatin expression, which was altered at the stage of decompensation in both models. In both models the results confirmed that animals reached a comparable stage of heart failure, therefore they could be used to study the gradual transition from compensatory hypertrophy to heart failure. Alterations regarding skeletal muscle impairment are more pronounced in left heart failure than in right heart failure. Generally, heart failure induced significant muscle atrophy, which was indicated by an impaired protein metabolism as well as mitochondrial dysfunction. The reason for these changes within the peripheral muscles after AOB is most probably the observed activation of the RAAS. Most changes appeared within the soleus and gastrocnemius muscle while the diaphragm was not impaired. The earliest signs of skeletal muscle impairment are the mitochondrial dysfunction and the upregulation of myostatin, which inhibits muscle growth. Differences regarding the diaphragm compared with the soleus und gastrocnemius are likely due to compensatory mechanisms as a result of increased muscle activity.