Definition, Etiology, PathogenesisTop
Hypertrophic cardiomyopathy (HCM) is a disease of the myocardium that is characterized by an increased left ventricular (LV) wall thickness (>15 mm in any myocardial segment) not explained by conditions that augment LV afterload. HCM is an autosomal dominant disease typically due to genetic mutation(s) of the sarcomeric proteins causing myocardial disarray.
Patterns of hypertrophy seen in HCM include:
1) Asymmetric hypertrophy of the interventricular septum, defined as a septal to posterior wall thickness ratio >1.3 in normotensive individuals or >1.5 in hypertensive individuals. This may result in systolic anterior motion (SAM) of the mitral valve and dynamic obstruction of the left ventricular outflow tract (LVOT).
2) Concentric (symmetric) hypertrophy, defined as an increase in LV wall thickness of all walls not explained by LV loading conditions or infiltrative disease.
3) Midventricular hypertrophy, which can give a “dumbbell” appearance to the LV and cause midcavitary obstruction, sometimes resulting in LV apical dilatation and aneurysm.
4) Apical hypertrophy, defined as apical wall thickness >15 mm or an apical to basal wall thickness ratio >1.3, can give a “spade” appearance to the LV.
Clinical Features and Natural HistoryTop
1. Symptoms: Exertional dyspnea, angina, palpitations, dizziness, syncope or presyncope (particularly in patients with LVOT obstruction).
2. Signs: In hypertrophic obstructive cardiomyopathy (HOCM) a systolic murmur may be heard over the left sternal border with radiation towards the right upper sternal border and the apex. The murmur can intensify with a decrease in preload (eg, during the Valsalva maneuver; after standing from a sitting, lying, or squatting position; or following the administration of nitroglycerin/amyl nitrite) and soften with an increase in afterload (passive elevation of a lower extremity, sitting, squatting, or clenching both fists).
3. Natural history depends on the type and severity of myocardial hypertrophy, LVOT gradient, and propensity for ventricular arrhythmia. Most patients have a good prognosis and do not experience complications. Those who do develop complications generally fall into one of 3 pathways: sudden cardiac death/ventricular arrhythmias, heart failure, or paroxysmal/chronic atrial fibrillation.
4. Risk factors for sudden cardiac death: Younger age at diagnosis, nonsustained ventricular tachycardia, LV myocardial thickness ≥30 mm, a family history of sudden cardiac death at a young age (<40 years), unexplained syncope, enlarged left atrial diameter, LVOT gradient >50 mm Hg, abnormal blood pressure response (drop) to exercise (in individuals aged ≤40 years). A calculator for the assessment of the risk of sudden cardiac death in the next 5 years, HCM Risk-SCD Calculator, can be found at www.doc2do.com/hcm/webHCM.html.
HCM is diagnosed morphologically on the basis of results of echocardiography or magnetic resonance imaging (MRI) showing features of myocardial hypertrophy ≥15 mm in a segment of a nondilated LV that cannot be explained only by an increased cardiac load. Genetic testing can be used to confirm the diagnosis and to assess for the presence of HCM in family members.
1. Electrocardiography (ECG): Nonspecific changes; pathologic Q waves, especially in inferior and lateral leads; left axis deviation; abnormal P waves (indicative of enlargement of the left atrium or both atria); in some patients, deep T-wave inversions in V2 to V4; features of LV hypertrophy; ventricular and supraventricular arrhythmias.
2. Holter ECG monitoring is performed to detect ventricular tachycardia, supraventricular tachycardia, and atrial fibrillation (particularly in patients with enlargement of the left atrium). It is also used to establish the need for an implantable cardioverter-defibrillator (ICD) in patients with symptoms of palpitations, dizziness, or unexplained syncope.
3. Echocardiography reveals myocardial hypertrophy, which may either be asymmetric involving the septum, concentric, midventricular, or apical. It should be noted that genotype-positive individuals, including those experiencing sudden cardiac death, may not have significant hypertrophy on imaging. In patients with asymmetric septal hypertrophy (ASH), there may be elongation of the mitral leaflets, SAM of the mitral apparatus, and LVOT gradient. HCM is considered obstructive when the peak gradient across the LVOT at rest or with provocation (eg, Valsalva maneuver, amyl nitrite) is >30 mm Hg. While there is typically impairment in systolic longitudinal function (detected using Doppler imaging or strain), the overall LV ejection fraction (LVEF) may be preserved. LV diastolic function is typically abnormal.
Echocardiography is recommended not only for an initial assessment of every patient suspected of having HCM but also—with ECG—as a screening study in relatives of patients with HCM. A stress echocardiogram may be undertaken to assess LVOT gradients in patients who do not have significant obstruction at rest and after the Valsalva maneuver or administration of amyl nitrite.
4. ECG stress test can be performed in patients with unexplained syncope or with symptoms of heart failure particularly to assess for systolic blood pressure decrease during exercise.
5. MRI is recommended when echocardiography results are equivocal. MRI can evaluate the morphology of the LV, LV size, diastolic impairment, and degree of myocardial fibrosis.
6. Computed tomography (CT) is recommended when echocardiography results are equivocal in patients with contraindications to MRI.
7. Coronary angiography is recommended in patients with a history of cardiac arrest, with sustained ventricular tachycardia, and in all patients ≥40 years of age in whom invasive treatment of hypertrophy of the interventricular septum is planned.
8. Genetic testing is recommended in all patients with HCM as well as in first-degree relatives of patients with HCM.
HCM should be differentiated from hypertensive heart disease and athletic heart. Differential diagnosis includes also infiltrative cardiomyopathies (eg, amyloidosis), iron overload, metabolic disorders (eg, Fabry disease, mitochondrial cytopathies, glycogen or lysosomal storage diseases), neuromuscular disease (eg, Friedreich ataxia), or syndromic disorders (eg, Noonan syndrome, LEOPARD syndrome).
1. Asymptomatic patients: Follow-up.
2. Symptomatic patients: Cardioselective beta-blockers in maximum tolerated doses, especially in patients with a postexercise LVOT gradient. The doses should be titrated on the basis of the observed efficacy and treatment tolerance. If beta-blockers are not tolerated or contraindicated, use verapamil in a dose gradually titrated up to a maximum tolerated dose. If symptoms persist with target-dose beta-blockers or verapamil, consider adding disopyramide at the maximum tolerated dose (while monitoring the QTc interval).Evidence 1Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of data. Sherrid MV, Shetty A, Winson G, et al. Treatment of obstructive hypertrophic cardiomyopathy symptoms and gradient resistant to first-line therapy with β-blockade or verapamil. Circ Heart Fail. 2013 Jul;6(4):694-702. doi: 10.1161/CIRCHEARTFAILURE.112.000122. Epub 2013 May 23. PubMed PMID: 23704138. Do not use vasodilators (including nitrates and phosphodiesterase inhibitors) and digitalis in patients with LVOT obstruction.
3. Patients with heart failure and LVEF >50% without LVOT obstruction: Consider a beta-blocker, verapamil, or diltiazem.
4. Patients with heart failure and LVEF <50%: Consider an angiotensin-converting enzyme inhibitor in combination with a beta-blocker. If symptoms and LVEF <50% persist, consider adding a mineralocorticoid-receptor antagonist.
5. Patients with concomitant atrial fibrillation: This may be poorly tolerated hemodynamically and restoration and maintenance of normal sinus rhythm using electrical or chemical cardioversion may be necessary. For chemical cardioversion, amiodarone is the treatment of choice. Management of anticoagulation in those patients follows the usual principles, although newer agents have not been studied in this specific population.
1. Septal myectomy: This is performed to relieve LVOT outflow obstruction. Indications include patients with severe symptoms who have a resting or postexercise peak LVOT gradient ≥50 mm Hg despite receiving maximal tolerated medical therapy. In patients with indications for a simultaneous valve repair (eg, mitral valve repair), septal myectomy is preferred.
2. Percutaneous alcohol septal ablation: This is performed by injecting absolute alcohol into a septal perforating arterial branch to induce infarction in a portion of the interventricular septum. Indications are the same as in septal myectomy, and clinical efficacy is similar.
3. Dual-chamber pacing (to facilitate cardiac synchrony) may be considered in patients who have refractory symptoms despite maximal medical therapy and in whom myectomy or alcohol septal ablation cannot be performed.Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness and imprecise (sparse) data. Qintar M, Morad A, Alhawasli H, et al. Pacing for drug-refractory or drug-intolerant hypertrophic cardiomyopathy. Cochrane Database Syst Rev. 2012 May 16;(5):CD008523. doi: 10.1002/14651858.CD008523.pub2. Review. PubMed PMID: 22592731.
4. ICD implantation is recommended in patients at high risk of sudden cardiac death (see Clinical Features and Natural History, above) and in patients who have survived cardiac arrest or have recurrent sustained ventricular tachycardia.Evidence 3Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to observational data but increased because of the effect size. Maron BJ, Shen WK, Link MS, et al. Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death in patients with hypertrophic cardiomyopathy. N Engl J Med. 2000 Feb 10;342(6):365-73. PubMed PMID: 10666426.
5. Heart transplantation is indicated in patients with end-stage heart failure or ventricular arrhythmia that does not respond to treatment.
1. In stable patients perform ECG, echocardiography, and 48-hour Holter monitoring every 12 to 24 months.
2. In patients with sinus rhythm with left atrial dimension ≥45 mm or new palpitations, perform 48-hour Holter monitoring every 6 to 12 months.
3. In patients with progressive symptoms, consider a symptom-limited ECG stress test yearly or every 2 to 3 years in those who are stable.
4. In asymptomatic patients with a gene mutation, perform evaluation (including ECG and transthoracic echocardiography) every 2 to 5 years in adults and every 1 to 2 years in children.