New Concepts and Therapies of Hypertrophic Cardiomyopathy View PDF

The prevalence of HCM in the general population is 1:500, making it the most common form of inherited heart disease. It is caused by pathogenic genetic variants in the heart muscle proteins of the sarcomere and is inherited autosomal dominantly, with a heterogeneous clinical presentation. LVOT obstruction (LVOTO) and diastolic dysfunction can cause progressive, life-limiting symptoms, atrial arrhythmias (atrial fibrillation and flutter), which can cause thromboembolic strokes, HF associated with systolic dysfunction and ventricular arrhythmias, which are the most common cause of sudden cardiac death [1]. In addition to pharmacological agents, invasive therapies include myectomy, alcohol septal ablation, and right ventricular pacemakers [2]. The conventional medical treatment for symptomatic patients consists of betablockers and non-dihydropyridine calcium channel blockers, which reduce myocardial energy demand. Other alternatives have been used, such as perhexiline, trimetazidine, and ranolazine which affect myocardial energy metabolism at different levels or inhibit the production of aldosterone [3]. In patients with persistent symptoms of LVOTO, invasive treatments include surgical myectomy, alcohol septal ablation, or right ventricular pacing. Recent cardio selective drugs have shown promising results in reducing obstruction and improving function, such as mavacamten, which inhibits myosin binding to actin [4]. The main modifiable cardiovascular risk factors can be reduced and prevented through physical conditioning, improving functional capacity, and reducing morbidity and mortality. Studies show that physical conditioning can benefit HCM patients and be safe, good tolerable, and beneficial, contradicting the sedentary lifestyle typically prescribed to them. It is the first systematic review and meta-analysis to evaluate how current therapies for HCM affect functional capacity and echocardiographic data [5-9]. As a hereditary condition characterized by LVH, HCM, cannot be fully explained by abnormal loading conditions [10]. Traditional treatment options for controlling the risks of dangerous disease progression and malignant ventricular arrhythmias have been limited [11]. A common inheritable cardiac disorder, HCM usually follows an autosomal dominant inheritance pattern. As a consequence of genetic and clinical diagnoses combined, the prevalence of LVH in the general population is approximately 1:500 subjects without cardiovascular diseases. Sarcomeric proteins are affected by multiple mutations in at least 14 genes [12]. There are over 1400 variants in at least 11 genes that contribute to HCM; however, nearly 70% occur either in the MYH7 gene, which encodes for the myosin heavy chain, or in the MYBPC3 gene, which encodes for the myosin binding protein C [13]. In addition to sarcomeric mutations, HCM can also occur as a part of a syndrome. Since targeted therapies are available for these conditions, it is essential that they are identified. HCM manifests LVH without any abnormal loading conditions. Clinical manifestations of HCM include a variety of pathological features, resulting from both the direct functional impact of the mutation and the secondary changes in function the affected myocardium undergoes as a result [14]. Variations in genetic makeup explain a significant part of the difference in outcomes among HCM patients. Despite similar outcomes, several researchers found that MYBPC3-related HCM has a higher long-term prevalence of systolic dysfunction than MYH7. Based on these observations, it may be possible to understand genotypephenotype correlations in HCM by analyzing the pathophysiology of clinical progression differently between the two subsets [15-17]. The clinical features of relatives with the same genetic mutation may also differ. It is therefore essential to tailor and individualize treatment approaches for patients with HCM. It is stated that Obstructive HCM (oHCM) has LVOTO, defined by continuous wave Doppler echocardiography with a peak LVOT gradient of 30 mmHg, and that a gradient of 50 mmHg at rest or stimulated is generally considered the threshold for septal reduction therapy in patients who are drug-resistant [18]. Patients with HCM are more likely to experience LVOTO at rest, as well as during exercise, Valsalva maneuver, and drug use. LVOT obstruction is a dynamic consequence of HCM, dependent on preload conditions and anatomy, that typically affects around 50% of patients. Furthermore, people with oHCM often experience symptoms of HF, such as shortness of breath, difficulty exercising, and angina. It is also possible for them to experience syncope or pre-syncope, particularly when exerting themselves or lifting something heavy [19-21]. HCM has been transformed from a rare and dangerous disease to a relatively common disorder with generally stable progression through clinical and preclinical research findings. The morbidity and mortality of HCM (including sudden death) are lower than those of other inherited heart muscle disorders. There are some individuals with HCM who may have a typical lifespan, but LVOTO, atrial fibrillation, or ventricular arrhythmias can greatly affect their prognosis and quality of life [22].