Metabolic cardiomyopathy: A review and pooled analysis of pathophysiology, diagnosis and clinical management

Cardiomyopathies (CM) are potentially fatal heart muscle diseases and one of the leading causes of heart failure as well as indication for heart transplantation.Understanding their pathogenesis is clinically relevant to improve diagnosis, management and consequently minimize the current unacceptably high mortality rates.Metabolic storage diseases are an important aetiology of CM but the classical morphofunctional definition and classification relegates metabolic CM to simply an aetiology of dilated, hypertrophy or restrictive CMs thereby undermining dedicated research and a specific understanding of aetiologic-specific diagnosis and clinical management.However, over the past decade, the contribution of metabolic remodelling to the development of myocardial dysfunction has received substantial research attention.It is now appreciated that progressive pathologic changes in cardiac metabolism may precede myocardial dysfunction, indicating that metabolic remodelling is an important early event in the progression of CM.Consequently, research continues to identify metabolic storage diseases and critical metabolic pathways that may be able to prevent or ameliorate disease progression, and as a result, immensely improving our understanding of the pathophysiologic mechanisms of metabolic CM.This article aggregates current published evidence on metabolic storage disorders frequently implicated as an aetiology of CM with a particular focus on their pathophysiology, clinical presentation, diagnosis and clinical management approaches, as well as highlights grey areas that may benefit from additional research.