Cardiac Remodelling Patterns and Proteomics: The Keys to Move Beyond Ejection Fraction in Heart Failure?

Cardiac remodelling is recognized as a major determinant of disease progression and outcomes in heart failure (HF) and has played a central role in the discovery of disease-modifying treatments for HF with a reduced ejection fraction (HFrEF).1 The sacubitril/valsartan outcome studies in HFrEF2 and in HF with preserved ejection fraction (HFpEF)3 have recently illustrated the limitations of using left ventricular ejection fraction (LVEF) thresholds to examine the extent of treatment efficacy in HF. It is time to move beyond ejection fraction. The early evidence on the importance of cardiac remodelling came from ischaemic models4 and much of the mechanistic evidence is still derived from similar models, although other models (such as rapid pacing) are used. These generally lead to eccentric cardiac remodelling, with eventual reduction in LVEF. HF is now recognized as a multisystem disease involving a vast array of structural, functional, electrophysiological, cellular, and molecular mechanisms.5 The availability of proteomics provides tools to explore the mechanisms involved in HF beyond LVEF and even cardiac remodelling. Aetiologic factors are changing over time, with lower proportions of patients having primarily ischaemic HF. Still, cardiac remodelling phenotypes will remain related to the clinical phenotypes (triggering events, toxic exposures, cardiovascular risk factors, co-morbid conditions, etc.), as will molecular mechanisms underlying the development and progression of HF. Left ventricular (LV) concentric remodelling or hypertrophy are typically seen in the pressure-overload models, remodelling phenotypes frequently observed in HFpEF,6 where one of the dominant co-morbid conditions is hypertension. In a recently published report examining mechanisms involved in HFpEF, the Olink Proseek Multiplex CVD II and III proximity extension assays