Hypertrophic cardiomyopathy: A complex disease
ABSTRACT
Hypertrophic cardiomyopathy (HCM) is a complex cardiovascular disease with wide phenotypic variations. Despite significant advances in imaging and genetic testing, more information is needed about the roles and implications of these resources in clinical practice. Patients with suspected or established HCM should be evaluated at an expert referral center to allow for the best multidisciplinary care. Research is needed to better predict the risk of sudden cardiac death in those judged to be at low risk by current risk-stratification methods.
KEY POINTS
- Obstruction of the left ventricular outflow tract is a key pathophysiologic mechanism in HCM.
- Because most of the genetic variants that contribute to HCM are autosomal dominant, genetic counseling and testing are suggested for patients and their first-degree relatives.
- Transthoracic echocardiography is the first-line imaging test, followed by magnetic resonance imaging.
- Beta-blockers are the first-line drugs for treating symptoms of HCM.
- An implantable cardioverter-defibrillator can be considered for patients at risk of sudden cardiac death.
- When medical therapy fails or is not tolerated in patients with severe symptoms of obstructive HCM, surgery to reduce the size of the ventricular septum can be considered. Alcohol septal ablation is an alternative.
Medical management: Beta-blockers, then calcium channel blockers
Beta-blockers are the first-line therapy for symptomatic HCM related to left ventricular outflow tract obstruction. Their negative inotropic effect reduces the contractile force of the ventricle, effectively reducing the pressure gradient across the outflow tract. Reduced contractility also means that the overall myocardial workload is less, which ultimately translates to a reduced oxygen demand. With their negative chronotropic effect, beta-blockers lower the heart rate and thereby lengthen the diastolic filling phase, allowing for optimization of preload conditions to help prevent increasing the left ventricular outflow tract gradient.37,38
Beta-blockers can be titrated according to the patient’s symptoms and tolerance. Fatigue and loss of libido are among the most common side effects.
Nondihydropyridine calcium channel blockers can be a second-line therapy in patients who cannot tolerate beta-blockers. Several studies have shown improvement in surrogate outcomes such as estimated left ventricular mass and QRS amplitude on electrocardiography, but currently no available data show that these drugs improve symptoms.28,39,40 They should be avoided in those with severe left ventricular outflow tract obstruction (gradient ≥ 100 mm Hg), as they can lead to critical outflow tract obstruction owing to their peripheral vasodilatory effect.
Dihydropyridine calcium channel blockers should be avoided altogether, as they produce even more peripheral vasodilation and afterload reduction than nondihydropyridine calcium channel blockers.
Disopyramide, a class IA antiarrhythmic, has been shown to effectively reduce outflow gradients and relieve symptoms. However, in view of its adverse effects, it is a third-line therapy, given to those for whom beta-blockers and calcium channel blockers have failed. Its most worrisome adverse effect is QT prolongation, and the QT interval should therefore be closely monitored at the start of treatment. Anticholinergic effects are common and include dry eyes and mouth, urinary retention, and drowsiness.
Disopyramide is usually used in combination with beta-blockers for symptom control as a bridge to a planned invasive intervention.41
Use with caution
Any medication that causes afterload reduction, peripheral vasodilation, intravascular volume depletion, or positive inotropy can worsen the dynamic left ventricular outflow tract obstruction in a patient with HCM and should be avoided.
Angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and nitrates must be used with extreme caution in these patients.
Diuretics. Even restrained use of diuretics can cause significant hemodynamic compromise in patients with obstructive physiology. Therefore, diuretics should be used sparingly in these patients.
Digoxin should not be used for managing atrial fibrillation in these patients, as its positive inotropic effect increases contractility and increases the left ventricular outflow tract gradient.
Norepinephrine and inotropic agents such as dobutamine and dopamine should be avoided for the same reason as digoxin. In patients with circulatory shock requiring vasopressor support, pure alpha-agonists such as phenylephrine are preferred, as they increase peripheral resistance without an inotropic effect.
Anticoagulation for atrial tachyarrhythmias
The risk of systemic thromboembolic events is significantly increased in HCM patients with atrial fibrillation or flutter, regardless of their estimated risk using conventional risk-stratification tools such as the CHADS2 score.42–44 In accordance with current American Heart Association and American College of Cardiology guidelines, we recommend anticoagulation therapy for all HCM patients with a history of atrial fibrillation or flutter. Warfarin is the preferred anticoagulant; direct oral anticoagulants can be considered, but there are currently no data on their use in HCM.9
Standard heart failure treatments
End-stage systolic heart failure is a consequence of HCM but affects only 3% to 4% of patients.45 While most randomized controlled trials of heart failure treatment have excluded HCM patients, current guidelines recommend the same evidence-based medical therapies used in other patients who have heart failure with reduced ejection fraction. This includes ACE inhibitors, ARBs, beta-blockers, and aldosterone antagonists if indicated.9,21
Heart transplant should be considered in patients with class III or IV New York Heart Association functional status despite optimization of their HCM treatment regimen. Heart transplant outcomes for HCM patients are comparable to outcomes for patients who receive a transplant for non-HCM cardiovascular disease.45,46
