What are the treatment options for Hypertrophic Cardiomyopathy (HCM) and associated complications?

From the Guidelines

The treatment for hypertrophic cardiomyopathy (HCM) should prioritize a multidisciplinary approach, incorporating medical therapy, surgical interventions, and lifestyle modifications to optimize symptom relief, reduce morbidity, and prevent sudden cardiac death, as recommended by the 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR guideline 1.

Medical Therapy

The primary goal of medical therapy is to alleviate symptoms and reduce outflow obstruction.

• First-line medical therapy typically involves beta-blockers (such as metoprolol 25-100 mg twice daily or atenolol 25-100 mg daily) or calcium channel blockers (verapamil 120-360 mg daily in divided doses) to reduce heart rate, improve diastolic filling, and decrease outflow obstruction, as outlined in the 2024 guideline 1.
• Non-dihydropyridine calcium channel blockers are preferred due to their ability to reduce outflow obstruction without causing vasodilation.
• For patients with persistent symptoms despite these medications, disopyramide (100-300 mg three times daily) may be added, or cardiac myosin inhibitors such as mavacamten can be considered, as they have been shown to decrease cardiac contractility and reduce left ventricular outflow tract obstruction 1.

Surgical Interventions

For severe obstructive HCM unresponsive to medications, septal reduction therapy is considered, either through:

• Surgical myectomy: a procedure that involves removing a portion of the thickened septal wall to reduce outflow obstruction.
• Alcohol septal ablation: a minimally invasive procedure that involves injecting alcohol into the septal artery to reduce the thickness of the septal wall. Both procedures can provide safe and effective symptomatic relief when performed by experienced HCM teams at dedicated centers, as highlighted in the 2024 guideline 1.

Lifestyle Modifications

Lifestyle modifications play a crucial role in managing HCM, including:

• Exercise stress testing to determine overall exercise tolerance and identify latent exercise-provoked left ventricular outflow tract obstruction, as recommended in the 2024 guideline 1.
• Healthy recreational exercise, such as light to moderate intensity activities, which has not been associated with increased risk of ventricular arrhythmia events in short-term studies 1.
• Avoiding rigorous exercise training for the purpose of performance or competition, especially in young patients, and engaging in careful planning to minimize risks.

Risk Stratification and Prevention

Assessing a patient's risk for sudden cardiac death is an essential component of management, and implantable cardioverter-defibrillators are recommended for patients at high risk, as outlined in the 2024 guideline 1.

• Patients with HCM and persistent or paroxysmal atrial fibrillation require oral anticoagulation with direct-acting oral anticoagulants or warfarin to reduce the risk of stroke, regardless of the CHA2DS2-VASc score, as recommended in the 2024 guideline 1. By prioritizing a multidisciplinary approach and individualizing treatment decisions based on symptom severity, degree of obstruction, and risk stratification for sudden cardiac death, patients with HCM can achieve optimal outcomes and improved quality of life, as supported by the 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR guideline 1.

From the FDA Drug Label

In 120 patients with hypertrophic cardiomyopathy (most of them refractory or intolerant to propranolol) who received therapy with verapamil at doses up to 720 mg/day, a variety of serious adverse effects were seen Three patients died in pulmonary edema; all had severe left ventricular outflow obstruction and a past history of left ventricular dysfunction. Eight other patients had pulmonary edema and/or severe hypotension; abnormally high (greater than 20 mmHg) pulmonary wedge pressure and a marked left ventricular outflow obstruction were present in most of these patients

The treatment options for Hypertrophic Cardiomyopathy (HCM) include:

• Verapamil: may be used in patients with HCM, but with caution, as it can cause serious adverse effects, such as pulmonary edema and severe hypotension, especially in patients with severe left ventricular outflow obstruction and a past history of left ventricular dysfunction 2
• Optimum doses of digitalis and/or diuretics: should be used to control milder ventricular dysfunction before verapamil treatment 2
• Alpha-adrenergic agents: such as phenylephrine HCl, metaraminol bitartrate, or methoxamine HCl, should be used to maintain blood pressure in patients with HCM, while isoproterenol and norepinephrine should be avoided 2
• Dopamine HCl or dobutamine HCl: may be administered if further support is necessary, depending on the severity of the clinical situation and the judgment and experience of the treating physician 2

From the Research

Treatment Options for Hypertrophic Cardiomyopathy (HCM)

• Medical management is the primary treatment approach for HCM, aiming to reduce symptoms and prevent sudden cardiac death (SCD) 3, 4.
• Pharmacologic treatment of symptoms in patients with HOCM consists of negative inotropic drugs, such as beta blockers and disopyramide, as well as non-dihydropyridine calcium channel blockers (CCBs), usually verapamil 3, 5.
• For patients with high left ventricular outflow tract (LVOT) gradients, the treatment of first choice is pharmacotherapy with nonvasodilating beta-blockers or non-dihydropyridine-type CCBs 5.
• Mavacamten, a myosin inhibitor, is a further option that lowers the LVOT gradient and improves quality of life 5.

Septal Reduction Therapy

• Septal reduction therapy, either surgical septal myectomy or alcohol septal ablation, can be considered for patients with severe symptoms unresponsive to medical therapy 3, 6.
• Surgical septal myectomy is highly effective, with a >90% relief of obstruction and improvement in symptoms, and a perioperative mortality rate of <1% 6.
• Alcohol septal ablation is a less invasive treatment, with comparable hemodynamic and clinical results to septal myectomy in many patients 6.

Management of Complications

• Attention must be paid to the management of sequelae such as atrial fibrillation, malignant arrhythmias, and mitral valve insufficiency 5.
• Patients with HCM have a near-normal life expectancy if the disease is diagnosed early and treated according to guidelines 5.
• Implantable cardioverter-defibrillators (ICDs) should be offered to patients at high risk of SCD 3.