Diagnostic yield of hypertrophic cardiomyopathy in first-degree relatives of decedents with idiopathic left ventricular hypertrophy

Former CRY Research Fellow Dr Gherado Finocchiaro completed a study into hypertrophic cardiomyopathy (HCM), aiming to determine the incidence of HCM in first-degree relatives of decedents from sudden death with idiopathic left ventricular hypertrophy.

The paper, entitled “Diagnostic yield of hypertrophic cardiomyopathy in first-degree relatives of decedents with idiopathic left ventricular hypertrophy” (Finocchiaro G et al. Europace) was published in August 2020, and Dr Finocchiaro provided us with an explanation of what the study involved and some of the key takeaways:

“Sudden cardiac death (SCD) in apparently healthy individuals is commonly due to a diverse spectrum of inherited cardiac diseases including cardiomyopathies and channelopathies. Autopsy is an essential preliminary diagnostic step to steer the clinical evaluation of surviving relatives towards inherited structural diseases or primary arrhythmogenic syndromes. The interpretation of the autopsy results, however, is often a complex task and uncertainty may exist about the precise significance of some pathological findings and their causal relationship with SCD.

“Idiopathic LVH is an increasingly recognized finding at autopsy of young decedents from SCD. The entity is used to describe unexplained LVH in the absence of myocardial disarray or secondary causes. Idiopathic LVH may be interpreted as HCM and targeted screening of first-degree relatives is recommended to detect others with quiescent disease. The significance and causal relationship of this entity with SCD is uncertain. Importantly, it is unclear whether idiopathic LVH represents the disease spectrum of HCM. Consequently, there are concerns that families of decedents with idiopathic LVH may be falsely reassured after limited evaluation with a 12-lead ECG and echocardiogram, which would be expected to identify the majority of individuals with HCM.

“With this CRY funded study, we aimed to investigate the significance of idiopathic LVH in decedents who experienced SCD through comprehensive clinical evaluation of their first-degree relatives and by conducting molecular autopsy in the decedents.

“Clinical evaluation of 125 first-degree relatives of 46 decedents with idiopathic LVH did not reveal a single case of HCM despite comprehensive clinical evaluation, including cardiovascular magnetic resonance (CMR) imaging, exercise testing, and prolonged ECG monitoring, which would be expected to identify even milder phenotypes of HCM. In contrast with none of the first-degree relatives being diagnosed with HCM, we found a 24% clinical diagnostic yield of inherited arrhythmia syndromes in family members of decedents with idiopathic LVH and a 14% yield of pathogenic variants in genes encoding cardiac myocyte ion channels at molecular autopsy. Specifically, Brugada syndrome was the most common diagnosis, followed by long QT syndrome.

“In summary, in this study, none of the family members of decedents with idiopathic LVH showed phenotypic features of HCM following comprehensive cardiovascular evaluation. Similarly, molecular autopsy in 14 decedents failed to reveal pathogenic variants in genes encoding sarcomeric proteins, which are commonly implicated in HCM. Therefore, idiopathic LVH and HCM are likely to represent two distinct pathological entities. The familial diagnosis of other cardiomyopathies and channelopathies in some families suggests that the presence of idiopathic LVH should prompt comprehensive assessment of families to encompass the broader spectrum of inherited structural heart disease and channelopathies.”

For more information, you can find this paper by clicking here.