Methods: Protein lysates and RNA prepared from cardiac muscle from colon 26 (C26) carcinoma bearing mice at day 14 post-tumour inoculation (i.e. 15-20% total body weight loss = overt cachexia) was used in this study. Gene and protein expression studies using quantitative Real Time Polymerase Chain Reaction (qRT-PCR) and Western blotting were performed on novel candidate markers of CC in heart, which may potentially be underpinning this process.Results: There was a significant up-regulation of RNA for Similar to Mother against Decapentaplegic homolog 4 (Smad4), Gata4 and B-cell lymphoma 2 (Bcl 2 ). Concurrently, a significant increase in protein expression of Smad4, Vitamin D receptor, and phosphorylated Extracellular Signalling Kinase 1 (p-Erk1); and significant decrease in protein expression of Gata4 and p-Erk2 was found.Conclusions: Our results suggest that cardiomyopathy resulting from cancer cachexia may be due to a series of maladaptive responses where alterations in molecular pathways regulated by Smad4, Gata4 and VDR occur simultaneously. Thus, these molecular targets may be potential biomarkers, which could be targeted for diagnosis and therapy.
BackgroundThe 2018 Australian Heart Failure (HF) guidelines strongly recommended commencing sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2is) in HF patients with type 2 diabetes mellitus (T2DM). The uptake of SGLT‐2is for HF patients with T2DM in our health service is unknown.AimsTo determine the adoption of the 2018 HF guidelines by assessing the temporal trends of SGLT‐2is' usage in HF patients with T2DM at Metro South Health (MSH) hospitals, in South‐East Queensland.MethodsRetrospective analysis of all HF patients (ejection fraction (EF) < 50%) with T2DM who were managed within MSH hospitals between June 2018 and June 2021.ResultsA total of 666 patients met the inclusion criteria with 918 HF encounters. Mean age was 72 years and 71% were male (473/666). Mean EF was 30% (SD ± 11%), and mean estimated glomerular filtration rate was 48 mL/min/1.73 m2 (SD ± 25). Fifty‐four per cent (362/666) had contraindications to SGLT‐2is. Among those without contraindications, there was a five‐fold increase in the utility of SGLT‐2is, 7% (2/29) before versus 38% (103/275) after implementation of the HF guidelines (P < 0.001). Patients on SGLT‐2is were younger (64 years vs 69 years, P = 0.002) and had a lower number of HF hospitalisations (1.1 vs 2.1, P = 0.01).ConclusionsDuring the study period, 54% of our HF patients with T2DM were not on SGLT‐2is due to prescribing guidelines/limitations in the Australian context. We observed a five‐fold significant increase in the uptake of SGLT‐2is before and after implementation of HF guidelines among patients without contraindications to SGLT‐2is. There were significantly fewer HF hospitalisations among patients on SGLT‐2is compared to those without.
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