Life-long tailoring of management for patients with hypertrophic cardiomyopathy : Awareness and decision-making in changing scenarios

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.

Keywords: Diagnosis; Hypertrophic cardiomyopathy; Imaging.

Fig. 1

a Stages of hypertrophic cardiomyopathy (adapted from [4]) and clinical characteristics. Mutation carriers (genotype positive/phenotype negative, G+/Ph−) may develop HCM (i. e. move to stage II) or remain without cardiac symptoms throughout their life (i. e. stable G+/Ph−). b Studies in mouse models and human cardiac samples revealed cellular changes which may be target for therapy to prevent onset of HCM (LVOTO Left ventricular outflow obstruction, LVEF LV ejection fraction, LA Left atrial, LGE Late gadolinium enhancement, AF Atrial fibrillation, NSVT Non-sustained ventricular tachyarrhythmias, SCD Sudden cardiac death)

Fig. 2

Progression of disease in patient case 1. a Progressive increase in cardiac dimensions, b a rise and subsequent decline in LVOTO, c a gradual decrease in MWT and d LV ejection fraction, e the different disease stages of the patient (LA Left atrium, LVESD Left ventricular end-systolic dimensions, LVEDD Left ventricular end-diastolic dimensions, LVOTO LV outflow tract obstruction, MWT Maximal wall thickness, LVEF LV ejection fraction [LVEF])

Fig. 3

Echocardiographic follow-up of case 1. Transthoracic echocardiogram of case 1 in 2005 (a–c) and 2015 (d–f). During 10 years of follow-up there was a gradual decrease of septal (*) and left ventricular posterior wall (▪) thickness and an increase of left ventricular dimension (●)

Fig. 4

Progression of disease in patient case 1. a Progressive increase in cardiac dimensions (LA Left atrium, LVESD and LVEDD Left ventricular end-systolic and end-diastolic dimensions), b decline in maximal wall thickness (MWT) and c a decline in LV ejection fraction (LVEF). d The different disease stages of the patient. e Cardio magnetic imaging at stage IV of the disease showing a dilated heart and extensive late gadolinium enhancement (arrow)