Introduction Left-sided heart failure (HF) is mainly the result of hypertension and coronary disease, whereas isolated right-sided HF results from a different set of conditions, including pulmonary arterial hypertension (PAH) and congenital heart disease. However, pump failure and arrhythmias are common in both types of HF. The aim of this study is to determine if inflammation, fibrosis and apoptosis are involved. Methods To induce PAH, monocrotaline (MCT, 60 mg/ml/kg) was injected subcutaneously into 200 g male Wistar rats. Weight-matched saline injected rats were used as controls. The rats were sacrificed ≤ 28 days later. To induce left-sided HF, rabbits underwent two surgical steps. First, volume overload was caused by aortic valve destruction, followed 3 weeks later by pressure overload by partial constriction of the abdominal aorta. Heart samples were frozen for qPCR analysis, histology and immunohistochemistry. Results qPCR analysis revealed a significant increase in mRNA levels of inflammatory cytokines, IL1β and TGFβ1, in the sinoatrial node (SAN), right atrium (RA), right ventricle (RV) and right Purkinje fibres (RPF) of the MCT-injected rats. There was an increase in mRNA levels of fibrosis markers, collagen1, elastin, fibronectin, CTGF and TIMP1, in the same tissues. There was an increase in collagen3 mRNA in the RA, RV and RPF. Vimentin mRNA increased in the SAN, RA and RV. In contrast, only modest changes were seen in the left side of the heart and a significant reduction in mRNA levels of collagens1 and 3, elastin, fibronectin and CTGF in the left ventricle (LV). Histology demonstrated proliferation of non-myocyte nuclei in the RV, but not the LV, in the MCT-injected rats. Immunohistochemisty revealed that these cells express vimentin and CD68, demonstrating they are macrophages and possibly fibroblasts. In the rabbit model, the RA demonstrated significant increases in mRNA levels of IL1β, TNF, NFκB and angiotensin II receptor 1 (AT1R). There was an increase in levels of the fibrosis markers MMP2 and TIMPs 1 and 2. The SAN demonstrated a significant increase in collagen3 and fibronectin, and a reduction in AT1R and TIMP3. There was an increase in fibronectin and TIMP1 in the RV, with no change in the LV. Fibronectin mRNA increased in the RPF, while AT1R and TIMP4 were reduced in the left Purkinje fibres (LPF). Conclusion In the rat model of right-sided HF, there was increased expression of inflammatory and fibrosis genes in the right side of the heart, including the SAN. This could contribute to dysfunction and predispose to arrhythmias in PAH. Unexpectedly, few changes were found in the LV and LPF in the rabbit left-sided HF model, the majority of changes occuring in the RA. The thin walled chambers of the heart, namely the RA and RV, could possibly be more susceptible to stretch as they mount an inflammatory response to HF triggers.