Current and emerging pharmacotherapy for the management of hypertrophic cardiomyopathy

by Selleckchem | Sep 03 2023

Introduction: Hypertrophic cardiomyopathy (HCM) is one of the most common genetic causes of heart disease. Since the initial description of HCM, there have been minimal strides in management options. Obstructive HCM constitutes a larger subset of patients with increased left ventricular outflow tract gradients causing symptoms. Septal reduction therapy (SRT) has been successful, but it is not the answer for all patients and is not disease modifying.

Areas covered: Current guideline recommendations include beta-blockers, calcium channel blockers, or disopyramides for medical management, but there lacks evidence of much benefit with these drugs. In recent years, there has been the emergence of cardiac myosin inhibitors (CMI) which have demonstrated positive results in patients with both obstructive and non-obstructive HCM. In addition to CMIs, other drugs have been investigated as we have learned more about HCM's pathological mechanisms. Drugs targeting sodium channels and myocardial energetics, as well as repurposed drugs that have demonstrated positive remodeling are being investigated as potential therapeutic targets. Gene therapy is being explored with vast potential for the treatment of HCM.

Expert opinion: The armamentarium of therapeutic options for HCM is continuously increasing with the emergence of CMIs as mainstays of treatment. The future of HCM treatment is promising.

Comments:

Hypertrophic cardiomyopathy (HCM) is a prevalent genetic heart disease, and its management has seen limited advancements since its initial description. Obstructive HCM, which is characterized by increased left ventricular outflow tract gradients causing symptoms, is a significant subset of patients. Septal reduction therapy (SRT) has been successful for some patients but is not universally effective and does not modify the underlying disease process.

Current guideline recommendations for medical management of HCM include beta-blockers, calcium channel blockers, or disopyramide, but the evidence for their effectiveness is limited. However, in recent years, there has been an emergence of cardiac myosin inhibitors (CMIs) that have shown positive results in both obstructive and non-obstructive HCM patients. These CMIs directly target the dysfunctional sarcomeric protein responsible for the disease, offering a novel therapeutic approach.

Furthermore, as our understanding of the pathological mechanisms of HCM has improved, other drugs targeting sodium channels and myocardial energetics have been investigated. These drugs aim to address the abnormalities in ion channel function and energy metabolism seen in HCM. Additionally, repurposed drugs that have shown positive remodeling effects in HCM are also being explored as potential therapeutic options.

Gene therapy holds immense promise for the treatment of HCM. By targeting the underlying genetic defects responsible for HCM, gene therapy has the potential to provide disease-modifying effects. Although gene therapy is still in the early stages of research and development, it represents a promising avenue for future treatment options.

Overall, the therapeutic options for HCM are continuously expanding, with CMIs emerging as mainstays of treatment. As our understanding of the disease improves, targeted therapies addressing specific pathophysiological mechanisms offer new hope for more effective management of HCM. The future of HCM treatment appears promising, with the potential for personalized medicine approaches and disease-modifying interventions on the horizon.