Proteomic profiling allows measurement of thousands of proteins simultaneously from blood or tissue samples in patients with cardiovascular disease which offers the promise of both improved risk prediction and identification of pathways instrumental in disease progression. In a multi-centre prospective cohort study of 389 patients with hypertrophic cardiomyopathy (HCM), Lumish and colleagues1 derived and validated an 11-protein proteomics-based model to predict worsening heart failure (HF) over a median follow-up of 2.8 years (IQR: 1.8–5.1) with 68 (17%) patients developing worsening HF symptoms. Based on the proteomics model, patients classified into high-risk (32 patients) vs low-risk (89 patients) groups had a significantly higher rate of worsening HF (HR=22.3; 95% CI, 5.1 to 97.7; p<0.0001). Analysis of the proteomics profile also showed that dysregulation of the Ras-MAPK and the upstream P13k-Akt pathway was present in patients with worsening HF (figure 1). Previously, this signalling pathway has been linked to HCM based on germline mutations, elevated mRNA levels, upregulations in more symptomatic patients, and prediction of late gadolinium enhancement on MRI but this is the first description of an association with progression of HF symptoms.

Pathway analysis of proteins that were differentially regulated between patients who developed worsening heart failure and those who did not. pathways with a false discovery rate (FDR)<0.001 with at least five associated proteins were considered positive (ie, dysregulated).Fcε RI, Fc-epsilon-RI; FoxO, …