Life-long tailoring of management for patients with hypertrophic cardiomyopathy

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, characterised by complex pathophysiology and extensive genetic and clinical heterogeneity. In most patients, HCM is caused by mutations in cardiac sarcomere protein genes and inherited as an autosomal dominant trait. The clinical phenotype ranges from severe presentations at a young age to lack of left ventricular hypertrophy in genotype-positive individuals. No preventative treatment is available as the sequence and causality of the pathomechanisms that initiate and exacerbate HCM are unknown. Sudden cardiac death and end-stage heart failure are devastating expressions of this disease. Contemporary management including surgical myectomy and implantable cardiac defibrillators has shown significant impact on long-term prognosis. However, timely recognition of specific scenarios – including transition to the end-stage phase – may be challenging due to limited awareness of the progression patterns of HCM. This in turn may lead to missed therapeutic opportunities. To illustrate these difficulties, we describe two HCM patients who progressed from the typical hyperdynamic stage of asymmetric septal thickening to end-stage heart failure with severely reduced ejection fraction. We highlight the different stages of this complex inherited cardiomyopathy based on the clinical staging proposed by Olivotto and colleagues. In this way, we aim to provide a practical guide for clinicians and hope to increase awareness for this common form of cardiac disease.

Sex-specific cardiac remodeling in early and advanced stages of hypertrophic cardiomyopathy

“…Stage IV patients show less hypertrophy of the IVS and increased dimensions of both LV and left atrium. [8] Both our patient groups showed a predominance of the male sex (stage II: 56% and stage IV: 60%) which is in line with earlier research (ranging from 55-72% in end-stage HCM). [25][26][27][28][29][30] As for stage II HCM patients, based on our recent study, we have proposed that women may be diagnosed too late because the cut-off value for IVS is not corrected by body surface area.…”

“…[6] To classify the different forms of HCM, Olivotto et al [7] described different stages in cardiac disease progression ranging from unaffected mutation carriers to end-stage failing HCM patients. [8] The majority of HCM patients develop a 'classic' (stage II) form of HCM with the characteristic septal thickening, LV outflow tract obstruction (LVOTO) and diastolic dysfunction. Approximately 5-10% of all HCM patients progress to the severe end-stage of HCM (stage IV), which is characterized by thinning of the IVS and LV wall, and left atrial dilation, extensive fibrosis and impaired systolic function.…”

Energetic drain driving hypertrophic cardiomyopathy

“…Clinical expression can be extremely diverse, ranging from symptomatic patients with severe hypertrophic remodeling accompanied by cellular disarray, fibrosis, and microvascular dysfunction, to asymptomatic mutation carriers with a structurally normal heart. Most patients display the classic form of HCM with asymmetric septal hypertrophy and left ventricle outflow tract obstruction at rest or during exercise . A small number of HCM individuals (~ 4%) progress to end‐stage HCM, defined by systolic dysfunction (ejection fraction <50%) and regression of hypertrophy and/or cavity dilation .…”

G3BP2 is involved in isoproterenol-induced cardiac hypertrophy through activating the NF-κB signaling pathway

“…Hypertrophy may initially be adaptive and help preserve systolic function, but sustained pathological hypertrophy will lead to a decompensated phase with deleterious consequences [1,2] . Epidemiological studies have revealed that cardiac hypertrophy is an independent risk factor for cardiac dysfunction and sudden death [3][4][5] . However, despite the great strides that have been made over the past decades in elucidating the pathogenesis of cardiac hypertrophy, the signaling pathways associated with this complex clinical syndrome are far from fully understood.…”