Definitional Challenges in Understanding Hypertrophic Cardiomyopathy

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiomyopathy. It is often caused by mutations of genes encoding for sarcomeric or sarcomere-associated proteins. Despite its clinical importance, divergent definitions are published by major cardiology societies. Some regard HCM as a specific genetic disease, whereas others define it as a broad 'spectrum of the thick heart'. The present narrative review aimed to assess both definitions from a pathoanatomical perspective. As a conjoint interdisciplinary and translational approach is needed to further increase knowledge and improve the understanding of HCM, the PubMed database was searched using several advanced search algorithms to explore the perspectives of the (forensic) pathologist, clinician, and basic researcher regarding the difference between the definitions of HCM. This discrepancy between definitions can impact critical data, such as prevalence and mortality rate, and complicate the understanding of the disease. For example, due to the different definitions, research findings regarding molecular changes from studies applying the narrow definition cannot be simply extended to the 'spectrum' of HCM.

Keywords: disease definition; hypertrophic cardiomyopathy; macroscopic pathoanatomy; myocardial structural alterations; obstructive hypertrophic cardiomyopathy.

Figure 1

Illustrated is a brief summary of the history of the HCM and how its definitions developed. Additionally, it shows which major classifications build the basis for the current HCM definitions provided by the AHA (orange) and the ESC (yellow). The outlined history follows the summary provided by Braunwald [2]. Other references underlying the figure: [1,3,4,5,6,7,8,10,11,16,18,19,23,24]. Abbreviations: AHA—American Heart Association; ESC—European Society of Cardiology; HCM—hypertrophic cardiomyopathy; RV—right ventricle.

Figure 2

A brief summary of pathoanatomical aspects of thickened myocardium and its differential diagnostic implications. The basic idea of the figure was inspired by the textbook Pathology of the Heart and Sudden Death in Forensic Medicine [83]. Other references underlying the present figure [26,27,37,38,60,72,73,74,84,85,86,87,88]. Abbreviations: AHA—American Heart Association; HCM—hypertrophic cardiomyopathy; IVS—interventricular septum.

Figure 3

Differences between the available major definitions of HCM provided by the ESC [8] and the AHA [7]. The term ‘umbrella diagnosis’ for the ESC definition of HCM was already introduced by Lillo et al. [19]. Abbreviations: AHA—American Heart Association; ESC—European Society of Cardiology; HCM—hypertrophic cardiomyopathy.