Abstract
Subaortic hypertrophic cardiomyopathy (HCM) is a genetic disease characterized by unexplained hypertrophy of the left ventricle that blocks blood flow from the heart. HCM has been linked with heart failure and an increased propensity for sudden cardiac death. The disease arises from a genetic mutation that affects the sarcomere protein, altering the myocardium’s structure and function by modifying the cardiomyocyte’s biophysical properties and causing irregular cellular metabolism. This implies that the disease is inherited from parents to their children, necessitating regular screening for individuals whose first-degree relatives are affected by the illness. HCM is increasingly asymptomatic; some individuals present signs of the disorder during early childhood, while others only exhibit the symptoms later in life.
Nevertheless, the common HCM symptoms include chest pain, dyspnea, dizziness, heart murmur, and sudden cardiac death. HCM progresses in distinct stages, each with its unique signs. The first stage is characterized by intermittent chest pain and increased fatigue following physical exercise.
In the second stage, patients experience acute diastolic dysfunction, atrial fibrillation, and microvascular malfunction. High morbidity and mortality cases mark the final phase. Its symptoms include severe left ventricular fibrosis, hemodynamic decompensation, and atrial dilation.
The diagnosis of HCM is typically conducted using various imaging techniques, including echocardiography, cardiac magnetic resonance imaging, and electrocardiography. The treatment approaches involve the use of diuretics, beta-blockers, disopyramide, and calcium channel blockers. Nevertheless, acute symptoms can be treated using septal reduction therapies, mainly surgical myomectomy or alcohol septal ablation, which reduces the blockage of the left ventricular outflow tract. Individuals with a genetic predisposition to HCM need regular screening to enable early diagnosis and treatment of the disease.
Keywords: left ventricular hypertrophy, gene mutation, obstruction, asymptomatic.
Introduction
Subaortic hypertrophic cardiomyopathy (HCM) is the most prevalent genetic heart disease. The disorder results from increased left ventricular hypertrophy, which blocks or reduces blood flow to the aorta. HCM affects one in every 500 individuals and has been linked to heart failure (Wolf, 2019). Although rare, it has also been established as the leading cause of sudden cardiac deaths among young people and exceptionally competitive athletes (Wolf, 2019). HCM is more prevalent in men than women, and by the time women are diagnosed with the disorder, they are older than men by an average of six years (Siontis et al., 2019).
Nevertheless, there are increased incidences of obstructive phenotype, severe diastolic function, and acute heart failure among women compared to men (Siontis et al., 2019). Thus, women may have a worse survival rate than men due to the late diagnosis and treatment. Subaortic HCM is caused by the gene mutation of the sarcomere protein, which alters the structure and functioning of the myocardium.
Causes and Risk Factors
Subaortic HCM is mainly inherited and can occur at any age. The condition results from a mutation in the gene responsible for the sarcomere protein, characterized by increased thickening of the left ventricular wall, which obstructs blood flow from the heart (Trongtorsak et al., 2021). Gene mutations alter the biophysical characteristics of cardiomyocytes, leading to irregular cellular metabolism. Research indicates that over 450 mutations in 20 myofilament and sarcomeric-related proteins have been connected to HCM (Wolf, 2019).
Nevertheless, many mutations affect the genes encoding myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) of the sarcomere (Wolf, 2019). Since HCM is hereditary, the risk factors include having a parent with the disorder. Individuals whose one of the parents has the condition have a 50% likelihood of experiencing the genetic mutation for HCM (Lafreniere-Roula et al., 2019). This implies that individuals whose first-degree relatives, including a parent, child, or sibling, have the disorder should be screened regularly for the ailment.
Symptoms
HCM is among the most underdiagnosed ailments due to its asymptomatic nature. Some individuals may present signs of the disorder in their childhood, while others may remain asymptomatic until the late stages of their lives (Wolf, 2019). Nevertheless, the common symptoms of HCM include chest pain (angina), fatigue, and shortness of breath during exercise (Wolf, 2019).
Similarly, the condition is characterized by dizziness, fainting, a heart murmur, and signs of heart failure. In some cases, the initial characteristic of the disorder may be sudden cardiac death resulting from malignant ventricular arrhythmias (Wolf, 2019). Therefore, patients with HCM are minimally asymptomatic, which may result in further progression of the condition.
Stages of Hypertrophic Cardiomyopathy
A pathogenic HCM mutation in the human body triggers a lifelong alteration process within the myocardium, progressing through distinct stages. The process begins with non-hypertrophic HCM, where individuals with HCM-causing mutations do not exhibit signs of thickening in their left ventricular muscle (Wolf, 2019). This may be classified as stage 0, mainly detected during genetic screening. At this stage, affected persons are considered “genotype-positive/phenotype-negative” (Wolf, 2019, p. S394).
The first stage of HCM is marked by the development of left ventricular hypertrophy (LVH), which causes obstruction and is characterized by mild signs, including irregular chest pain and low exercise tolerance (Wolf, 2019). Stage two of HCM is marked by severe myocardial restructuring with increased LVH and fibrotic alterations. It is also characterized by moderate to severe diastolic dysfunction, microvascular dysfunction, atrial dilatation, thin left ventricular (LV) walls, and the onset of atrial fibrillation (Wolf, 2019). Hence, each stage has its unique characteristics, which require specialized management.
The symptoms become more severe as the disorder progresses to its final stage. The third stage presents the irreversible end-stage of HCM with increased morbidity and mortality. Its symptoms include acute LV fibrosis, atrial dilation, increased LV dilation, and systolic and diastolic malfunction concomitant with heart failure, hemodynamic decompensation, or death (Wolf, 2019). It is crucial to note that the onset of HCM typically occurs between 20 and 50 years of age, although some individuals may present symptoms in childhood, while others may experience them later in life (Wolf, 2019). Therefore, regular screening is recommended for individuals predisposed to the illness to enable early detection and management of the disorder and avert incidences of mortality.
Diagnosis
Since the disorder is primarily inherited, an individual’s family history is crucial in determining their predisposition. Additionally, if a physician’s examination of a patient’s lungs and heart reveals a murmur, it could indicate a problem with blood flow through the heart, suggesting HCM. Nevertheless, HCM diagnosis is usually conducted using an echocardiogram, which examines the thickness of the heart’s muscles and blood flow through the heart (Wolf, 2019). In some scenarios, the transthoracic echocardiogram (TTE) may be used (Wolf, 2019). TTE analyzes cardiac morphology, diastolic, and systolic functions to assess the presence and severity of any left ventricular outflow tract (LVOT) gradient and the intensity of mitral regurgitation.
HCM can also be diagnosed using various other tests. These may include cardiac magnetic resonance imaging (MRI), genetic testing, and electrocardiogram (ECG) (Mestres et al., 2018). Genetic testing is mainly used for family screening and to confirm phenocopies. Additionally, ambulatory ECG monitoring needs to be conducted for 24 to 48 hours for all patients with HCM to assess the risk of ventricular arrhythmias and sudden death. Similarly, Holter and event monitors can identify abnormal heart rhythms (Carrington et al., 2022).
Moreover, stress tests are critical for risk stratification and to assess the LVOT gradient. Furthermore, some patients may also require a cardiac catheterization to assess the structure of the coronary vessels, cardiac hemodynamics, and the extent of left ventricular outflow blockage (Wolf, 2019). In some cases, electrophysiological studies may be performed to identify the origin of the arrhythmias.
Nevertheless, some diseases may present similar symptoms to those of HCM. Therefore, secondary causes of left ventricular hypertrophy, including drug toxicity, arterial hypertension, and structural heart disorder, should be ruled out before making an HCM diagnosis (Wolf, 2019). Other multisystem complications, such as neuromuscular, metabolic, neurologic, endocrinologic, or autoimmune diseases, as well as genetic disorders, can mimic HCM. They should be assessed since they require unique management depending on their etiology (Wolf, 2019). Thus, the diagnosis of HCM is determined by linking the increased hypertrophy of the heart muscle to mutations in the cardiac sarcomere.
Treatment
Several approaches are used to treat HCM based on a patient’s symptoms. Beta-blockers are used as first-line agents, effectively reducing exercise-induced obstruction in this case (Argirò et al., 2021). In addition, calcium channel blockers, such as Verapamil or Diltiazem, may be used as an alternative to beta blockers if a patient exhibits signs of intolerance or if beta blockers are proven to be inefficient (Argirò et al., 2021). Similarly, a combination of beta-blockers or calcium channel blockers with disopyramide is required for patients with refractory symptoms. Disopyramide effectively lessens the LV contractibility and subaortic gradient (Argirò et al., 2021). It also decelerates LV ejection and lowers resting and provokable gradient.
Nevertheless, using disopyramide has several side effects, including constipation, blurred vision, dry mouth, and urinary retention, which may deter patient compliance (Argirò et al., 2021). Furthermore, diuretics may be used to ease the symptoms of HCM, although they are recommended in small doses to prevent hypovolaemia (Wolf, 2019). Thus, various treatment plans may help ameliorate the symptoms of HCM.
Acute health complications linked to HCM may necessitate more rigorous treatment methods. In this case, a septal reduction therapy may be recommended for patients with adverse HCM symptoms and an LV outflow gradient of greater than 50 mmHg (Mestres et al., 2018). This therapy involves surgical septal myomectomy or alcohol septal ablation (ASA).
When conducted by experienced professionals, surgical myomectomy is more effective in reducing obstruction and improving symptoms of HCM. This procedure has low mortality and a high survival rate (Mestres et al., 2018). Alternatively, ASA is less invasive and reduces the blockage of the LVOT, but may still present residual obstruction (Mestres et al., 2018). Hence, the treatment approach used for HCM patients depends on the intensity of the symptoms.
Conclusion
In conclusion, subaortic HCM is a common genetic disorder characterized by unexplained left ventricular hypertrophy that blocks blood flow from the aorta. It is provoked by a gene mutation in the sarcomere protein, which impacts the myocardium. HCM is highly asymptomatic, but its common symptoms include chest pain, dizziness, shortness of breath, and a heart murmur. The disorder can be diagnosed using an echocardiogram, ECG, MRI, and genetic testing.
The treatment approaches include diuretics, beta-blockers, disopyramide, and calcium channel blockers. However, septal reduction therapies may be required for patients with advanced symptoms. In this case, surgical myomectomy and alcohol septal ablation have proven effective in lessening the blockage in the LVOT and easing the signs of the disease. Therefore, individuals predisposed to HCM should undergo regular screening to help detect the disorder at an early stage to facilitate effective treatment.
References
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