From the Guidelines
Yes, there are non-genetic causes of hypertrophic cardiomyopathy (HCM), and identifying these causes is crucial for proper diagnosis and management, as treatment approaches may differ from genetic HCM cases and some forms may be reversible if the underlying cause is addressed. While most cases of HCM are caused by genetic mutations affecting cardiac muscle proteins, several non-genetic factors can lead to this condition. These include:
- Aging-related changes, where long-standing hypertension causes the heart muscle to thicken as a compensatory mechanism
- Chronic kidney disease, which can contribute to HCM through increased cardiac workload and metabolic disturbances
- Athletic training, particularly in elite athletes, can cause physiological cardiac hypertrophy that may mimic HCM but typically resolves with detraining
- Infiltrative disorders such as amyloidosis, Fabry disease, and glycogen storage diseases can cause wall thickening resembling HCM
- Hormonal disorders including acromegaly (excess growth hormone) and pheochromocytoma (excess catecholamines) may induce cardiac hypertrophy
- Newborns of diabetic mothers can develop transient hypertrophy due to fetal exposure to maternal hyperglycemia
According to the most recent guideline, approximately 50% of cases of HCM are genetically elusive, suggesting that non-genetic factors play a significant role in the development of HCM 1. The 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy also highlights the importance of considering non-genetic causes of LV hypertrophy, such as systemic disorders and secondary causes of LVH 1. The 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy provides further insight into the genetic and clinical diagnosis of HCM, but also acknowledges the existence of non-genetic causes of LV hypertrophy 1.
In clinical practice, it is essential to consider these non-genetic causes of HCM to provide accurate diagnosis and management, and to improve patient outcomes in terms of morbidity, mortality, and quality of life.
From the Research
Non-Genetic Causes of Hypertrophic Cardiomyopathy (HCM)
There is limited evidence to suggest non-genetic causes of Hypertrophic Cardiomyopathy (HCM). The majority of studies suggest that HCM is a genetic disorder caused by mutations in sarcomeric genes, leading to left ventricular hypertrophy and complex phenotypic heterogeneity 2, 3, 4, 5, 6.
Genetic Causes of HCM
- HCM is caused by mutations in genes encoding sarcomere-associated proteins, with MYH7 and MYBPC3 being the most common genes involved 2, 3, 6
- Mutations in these genes lead to altered biophysical properties of the cardiomyocyte, disturbed calcium handling, and abnormal cellular metabolism 3
- Genetic diagnosis allows for the identification of asymptomatic affected patients prior to clinical disease onset, and regular clinical follow-up, family counseling, and preventative treatment are required to minimize morbidity and mortality of affected patients 3, 6
Clinical Manifestations of HCM
- HCM can manifest as left ventricular hypertrophy in the absence of a secondary cause, with a diverse natural history ranging from asymptomatic to heart failure or sudden cardiac death 2, 5, 6
- Left ventricular outflow tract obstruction is present at rest in about one third of patients and can be provoked in another third 2
- The clinical course of the disease varies greatly, with some patients presenting during childhood while others remain asymptomatic until late in life 3