Hypertrophic cardiomyopathy is a common genetic heart disease characterized by left ventricular hypertrophy in the absence of a valvular, systemic, or metabolic cause. In addition to its hemodynamic consequences, hypertrophic cardiomyopathy predisposes to arrhythmias, including bradyarrhythmias, atrial and ventricular tachyarrhythmias, and sudden death, and eventually end-stage dilated cardiomyopathy. Arrhythmias may cause palpitations, syncope, and/or cardiac arrest. Diagnosis includes ECG, cardiac imaging, and genetic testing. Treatment is usually an implantable cardioverter-defibrillator (ICD), antiarrhythmic pharmacotherapy, and measures for heart failure.
(See also Overview of Arrhythmogenic Cardiomyopathies and Overview of Arrhythmias.)
Hypertrophic cardiomyopathy in general is reviewed elsewhere in THE MANUAL. This topic focuses on its arrhythmogenic features.
Hypertrophic cardiomyopathy is a congenital or acquired disorder characterized by marked ventricular hypertrophy with diastolic dysfunction in the absence of increased afterload (eg, not due to valvular aortic stenosis, coarctation of the aorta, systemic hypertension).
Inherited hypertrophic cardiomyopathy is a common (1/500) cardiac disorder (1), usually autosomal dominant with variable penetrance. The underlying etiology is one of more than 1500 reported mutations in genes encoding myofilament proteins of the sarcomere. Genetic testing is positive in 40 to 60% of patients with hypertrophic cardiomyopathy (2).
The phenotype is very diverse but typically is characterized by left ventricular hypertrophy (LVH) often accompanied by left ventricular outflow tract obstruction, atrial tachyarrhythmias, ventricular tachyarrhythmias, sudden death, and end-stage dilated cardiomyopathy (3). The LVH is typically asymmetrical, in which the anterior septum and anterior free wall are hypertrophied much more than is the posterior wall. Nevertheless, subtypes with concentric left ventricular hypertrophy or isolated left ventricular apical hypertrophy are recognized. Cardiac function is compromised because hypertrophy results in a stiff, noncompliant left ventricle that resists diastolic filling, elevating end-diastolic pressure and thus increasing pulmonary venous pressure. As resistance to filling increases, cardiac output decreases, an effect worsened by any outflow tract gradient present. Because tachycardia allows less time for filling, symptoms tend to appear (or worsen) mainly during exercise or tachyarrhythmias. (See also Heart failure with preserved ejection fraction.)
In regards to arrhythmias, the hypertrophy is associated with myofibril disarray, microvasculopathy, microvascular insufficiency, ischemia, and myocardial scarring, all of which predispose to ventricular tachyarrhythmias and sudden death. Atrial fibrillation is also very frequent and may be particularly poorly tolerated secondary to aggravation of ventricular diastolic dysfunction by rapid ventricular rates.
Symptoms and signs often are exertional and include dyspnea, chest pain (usually resembling typical angina), palpitations, and syncope. The syncope may be caused by arrhythmia or outflow tract obstruction.
Довідкові матеріали загального характеру
1. McKenna WJ, Judge DP: Epidemiology of the inherited cardiomyopathies. Nat Rev Cardiol 18(1):22–36, 2021. doi:10.1038/s41569-020-0428-2
2. Girolami F, Gozzini A, Pálinkás ED, et al: Genetic Testing and Counselling in Hypertrophic Cardiomyopathy: Frequently Asked Questions. J Clin Med 12(7):2489, 2023. doi:10.3390/jcm12072489
3. Ottaviani A, Mansour D, Molinari LV, et al: Revisiting Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Current Practice and Novel Perspectives. J Clin Med 12(17):5710, 2023. doi: 10.3390/jcm12175710.
Diagnosis of Hypertrophic Cardiomyopathy Arrhythmias
ECG, echocardiography, and often cardiac MRI
Often ambulatory cardiac monitoring
Genetic testing
Screening of first-degree family members
The diagnosis of hypertrophic cardiomyopathy is suggested by an ECG showing left ventricular hypertrophy and by characteristic clinical findings on physical examination. Diagnosis is confirmed by cardiac imaging, usually transthoracic echocardiography showing left ventricular hypertrophy, particularly asymmetrical left ventricular hypertrophy. A cardiac magnetic resonance examination using gadolinium is done if required to establish the diagnosis or to quantify left ventricular scarring when needed to further assess risk of sudden cardiac death.
Arrhythmia evaluation usually includes ambulatory cardiac rhythm monitoring and exercise testing.
Patients also should have regular (eg, annual) clinical follow-ups, including ECG, echocardiography, ambulatory cardiac rhythm monitoring, and exercise testing.
Although genetic testing has a low sensitivity, it is still recommended to allow cascade screening of family members. Nevertheless, whether genetic findings predict future life-threatening arrhythmias remains unclear. Family members also should have clinical evaluation (ie, to detect symptoms suggestive of arrhythmia and/or heart failure), ECG, and echocardiography.
The diagnosis of hypertrophic cardiomyopathy includes considering, and ruling out, other disorders that produce similar cardiac findings (phenocopies), including hypertensive heart disease, athlete's heart, cardiac amyloid, and Anderson-Fabry disease (1).
Довідковий матеріал щодо діагностики
1. Ottaviani A, Mansour D, Molinari LV, et al. Revisiting Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Current Practice and Novel Perspectives. J Clin Med 12(17):5710, 2023. doi: 10.3390/jcm12175710.
Treatment of Hypertrophic Cardiomyopathy Arrhythmias
Moderation of physical activity
For atrial fibrillation, antiarrhythmic pharmacotherapy and anticoagulation for stroke prevention
For ventricular arrhythmias, often an implantable cardioverter-defibrillator (ICD)
Heart failure therapy (including transplantation) as required
Outflow tract obstruction therapy as required (usually a beta-blocker but sometimes septal myomectomy, septal alcohol ablation, or cardiac myosin inhibitor therapy)
Patients with hypertrophic cardiomyopathy have typically been advised to avoid athletic exertion because such activities foster life-threatening arrhythmias and may hasten disease progression. However, current guidelines recommend that patients may continue to pursue recreational athletic activity after a comprehensive evaluation and shared discussion with an expert specialist in hypertrophic cardiomyopathy of potential risk (and the understanding that individual exercise risk cannot be precisely predicted [1]).
Standard measures for treatment of hypertrophic cardiomyopathy include beta-blockers and heart rate-limiting calcium channel blockers. On occasion, right ventricular pacing is used to treat outflow tract obstruction by purposefully inducing interventricular dyssynchrony. Cardiac resynchronization pacing therapy may be required in patients who have progressed to a dilated cardiomyopathy.
For atrial tachyarrhythmias, standard treatment is used: rate-control with negative dromotropic medications (usually a beta-blocker), rhythm control (usually with amiodarone), and thromboembolic risk reduction (usually with warfarin or a direct acting oral anticoagulant).
For ventricular arrhythmias, prevention of sudden death is with an ICD, which is recommended for patients with dilated cardiomyopathy and left ventricular ejection fraction of ≤ 35% and for patients with sustained ventricular tachycardia/ventricular fibrillation or resuscitated cardiac arrest. Because of the higher risk of sudden death in patients with hypertrophic cardiomyopathy, guidelines also that an ICD can be useful for patients with one or more of the following: sudden cardiac death in a close relative at age ≤ 50 years, left ventricular wall thickness ≥ 30 mm, syncope considered to be due to an arrhythmia, left ventricular apical aneurysm, or left ventricular ejection fraction < 50% (class IIa recommendation) and may be considered for patients with extensive late gadolinium enhancement (LGE) on cardiac MRI (a marker of ventricular scarring) or documented nonsustained ventricular tachycardia. (Class IIb recommendation) (1) (see table Indications for Implantable Cardioverter-Defibrillators). Antiarrhythmic medications, usually amiodarone, are used to control frequently recurrent ventricular tachyarrhythmias leading to frequent ICD interventions, particularly ICD shocks. Transcatheter ablation of the arrhythmogenic substrate may also be used (1).
Outflow tract obstruction also may be helped by beta-blockers and sometimes septal reduction therapy (surgical or by alcohol ablation) or cardiac myosin adenosine triphosphatase inhibition with mavacamten.
Довідковий матеріал щодо лікування
1. Ommen SR, Mital S, Burke MA, et al: 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 142(25):e533–e557, 2020. doi: 10.1161/CIR.0000000000000937
Ключові моменти
Hypertrophic cardiomyopathy is arrhythmogenic, predisposing to atrial and/or ventricular tachyarrhythmias and sudden death.
Cases may be inherited or acquired.
Diagnosis is by ECG, echocardiography, and often cardiac MRI.
Atrial tachyarrhythmias are treated with medications and ventricular dysrhythmias with an implantable cardioverter-defibrillator (ICD).
Exercise is not strictly prohibited provided appropriate evaluation and shared decision-making are done.
