Hypertrophic cardiomyopathy (HCM, or HOCM when obstructive) is a condition in which muscle tissues of the heart become thickened without an obvious cause. The parts of the heart most commonly affected are the interventricular septum and the ventricles. This results in the heart being less able to pump blood effectively and also may cause electrical conduction problems. Specifically affected are the bundle branches that conduct impulses through the interventricular septum and into the Purkinje fibers, as these are responsible for the depolarization of contractile cells of both ventricles.
People who have hypertrophic cardiomyopathy may have a range of symptoms. People may be asymptomatic, or may have fatigue, leg swelling, and shortness of breath. It may also result in chest pain or fainting. Being dehydrated may aggravate the symptoms. Complications may include heart failure, an irregular heartbeat, and sudden cardiac death.
Hypertrophic cardiomyopathy is most commonly inherited in an autosomal dominant pattern. It is often due to mutations in certain genes involved with making heart muscle proteins. Other inherited causes of left ventricular hypertrophy include Fabry disease and Friedreich's ataxia. Other considerations for causes of an enlarged heart are athlete's heart and hypertension (high blood pressure). Making the diagnosis of hypertrophic cardiomyopathy often involves a family history or pedigree, an electrocardiogram, echocardiogram, and stress testing. Genetic testing is recommended for affected people and their family members. Hypertrophic cardiomyopathy can be distinguished from other inherited causes of cardiomyopathy by its autosomal dominant pattern, whereas Fabry disease is X-linked, and Friedreich's ataxia is inherited in an autosomal recessive pattern.
Treatment depends on symptoms and other risk factors. Medications may include beta blockers, verapamil, disopyramide, mavacamten or aficamten. An implantable cardiac defibrillator may be recommended in those with certain types of irregular heartbeat. Surgery, in the form of a septal myectomy or heart transplant, may be done in those who do not improve with other measures. With treatment, the risk of death from the disease is less than one percent per year.
Hypertrophic cardiomyopathy affects up to one in 500 people. People of all ages may be affected. The first modern description of the disease was by Donald Teare in 1958.
Signs and symptoms Many people with hypertrophic cardiomyopathy are asymptomatic or mildly symptomatic, and many of those carrying disease genes for hypertrophic cardiomyopathy do not have clinically detectable disease. The symptoms of hypertrophic cardiomyopathy include shortness of breath due to stiffening and decreased blood filling of the ventricles, exertional chest pain (also known as angina) due to reduced blood flow to the coronary arteries, uncomfortable awareness of the heart beat (palpitations), lightheadedness, weakness, fainting, and sudden cardiac death.
Shortness of breath is largely due to increased thickness of the left ventricle (LV) wall and interventricular septal wall, which impairs the filling of the ventricles, but also leads to elevated pressure in the left ventricle and left atrium as a result of increased thickness. This impaired heart filling can cause blood to back up in the lungs' circulation, causing further symptoms. Often, symptoms of hypertrophic cardiomyopathy are due to congestive heart failure (especially activity intolerance and dyspnea), but also lower extremity edema.
Major risk factors for sudden death in individuals with hypertrophic cardiomyopathy include prior history of cardiac arrest or ventricular fibrillation, spontaneous sustained ventricular tachycardia, abnormal exercise blood pressure and non-sustained ventricular tachycardia, unexplained syncope, family history of premature sudden death, and left ventricular wall thickness greater than 15 mm to 30 mm, on echocardiogram.
Hypertrophic cardiomyopathy also presents with a systolic ejection murmur that increases in intensity with decreased preload (as in the Valsalva maneuver or standing), or with decreased afterload (as in vasodilator administration). On the other hand, the murmur decreases in intensity with increased preload (as in squatting) or increased afterload (as in the handgrip maneuver). "Spike and dome" pulse and "triple ripple apical impulse" are two other signs that can be discovered in physical examination. Pulsus bisferiens may also be found during examination.
Genetics +Genetic basis Gene Locus Type MYH7 14q12 CMH1 () TNNT2 1q32 CMH2 () TPM1 15q22.1 CMH3 () MYBPC3 11p11.2 CMH4 () ? ? CMH5 PRKAG2 7q36 CMH6 () TNNI3 19q13.4 CMH7 () MYL3 3p CMH8 () TTN 2q24.3 CMH9 () MYL2 12q23-q24 CMH10 () ACTC1 15q14 CMH11 () CSRP3 11p15.1 CMH12 () Familial hypertrophic cardiomyopathy is inherited as an autosomal dominant trait which is attributed to mutations in one of several genes that encode for the sarcomere proteins, and most diagnosed individuals will have an affected parent. Occasionally, both copies of the gene will be defective, a condition that may lead to a more severe manifestation of the disease.
Currently, about 40–60% of people with hypertrophic cardiomyopathy will have a mutation identified in at least one of nine sarcomeric genes. Approximately 40% of these mutations occur in the β-myosin heavy chain gene on chromosome 14 q11.2-3, and approximately 40% involve the cardiac myosin-binding protein C gene. Since hypertrophic cardiomyopathy is typically an autosomal dominant trait, children of a single hypertrophic cardiomyopathy parent have a 50% chance of inheriting the disease-causing mutation. Whenever such a mutation is identified, family-specific genetic testing can be used to identify relatives at risk for the disease, although clinical severity and age of onset cannot be predicted.An insertion/deletion polymorphism in the gene encoding for angiotensin converting enzyme (ACE) alters the clinical phenotype of the disease. The D/D (deletion/deletion) genotype of ACE is associated with more marked hypertrophy of the left ventricle and may be associated with a higher risk of adverse outcomes.
Over 1400 mutations have been identified in genes known to lead to hypertrophic cardiomyopathy. Some mutations could have more harmful potential compared to others (β-myosin heavy chain). For example, troponin T mutations were originally associated with a 50% mortality before the age of 40. However, a more recent and larger study found a similar risk to other sarcomeric protein mutations. The age at disease onset of hypertrophic cardiomyopathy with MYH7 mutations is earlier and leads to more severe symptoms. Moreover, mutations on troponin C can alter Ca+2 sensibility on force development in cardiac muscle, these mutations are named after the amino acid that was changed after the location in which it happened, such as A8V, A31S, C84Y and D145E.
Pathophysiology Ventricular hypertrophy causes a dynamic pressure gradient across the left ventricular outflow tract (LVOT), which is associated with further narrowing of the outflow during systole. Pulling of the mitral valve leaflets towards the septum contributes to the outflow obstruction. This pulling is thought to occur by several proposed mechanisms, including the flow of blood through the narrowed outflow tract resulting in a higher velocity, and less pressure via the Venturi effect. This low pressure then causes the anterior leaflet of the mitral valve to be pulled into the outflow tract, resulting in further obstruction.
The hypertrophied (thickened) left ventricular wall in hypertrophic cardiomyopathy requires a greater oxygen demand. This increased oxygen demand of the enlarged heart muscle, combined with fibrosis (scarring) of the heart muscle and a reduced flow through thick-walled coronary arteries results in an oxygen deficit to the heart muscle. These pathophysiological changes result in the anginal (exertional chest pain) symptoms sometimes seen in hypertrophic cardiomyopathy.
Diagnosis
A diagnosis of hypertrophic cardiomyopathy is based upon several features of the disease process. While there is use of echocardiography, cardiac catheterization, or cardiac MRI in the diagnosis of the disease, other important considerations include ECG and genetic testing. Genetic testing is recommended for those affected by hypertrophic cardiomyopathy and their family members. In about 60 to 70% of the cases, cardiac MRI shows thickening of more than 15 mm of the lower part of the ventricular septum. T1-weighted imaging may identify scarring of cardiac tissues while T2-weighted imaging may identify edema and inflammation of cardiac tissue which is associated with acute clinical signs of chest pain and fainting episodes.
ECG is the most sensitive diagnostic test.
Differentiating obstructive from non-obstructive HCM is important for choosing effective therapy. A confusing aspect of HCM is that obstruction may be latent at rest, and only revealed by provocations. Exercise echocardiography, performing an echocardiogram after treadmill or bicycle exercise, may reveal obstruction when it is not present at rest or after the Valsalva maneuver. Even a more potent provocation of latent obstruction is the postprandial exercise echocardiogram (PPXSE) that is the strongest physiologic provocation of obstruction. The PPXSE reproduces the situation that many patients with obstruction experience, that of enhanced symptoms with even mild exertion after eating. When a patient cannot exercise, resting echocardiography performed 30–60 minutes after eating may similarly demonstrate obstruction, not shown at rest. With postprandial provocation, patients who previously were diagnosed as non-obstructive now are diagnosed as obstructed and thus may be candidates for treatments geared to obstruction.
Variants Depending on whether the distortion of normal heart anatomy causes an obstruction of the outflow of blood from the left ventricle of the heart, hypertrophic cardiomyopathy can be classified as obstructive or non-obstructive. The obstructive variant of hypertrophic cardiomyopathy is hypertrophic obstructive cardiomyopathy (HOCM). The diagnosis of left ventricular outflow tract obstruction is usually made by echocardiographic assessment and is defined as a peak left ventricular outflow tract gradient of ≥ 30 mmHg.
Another, non-obstructive variant of hypertrophic cardiomyopathy is apical hypertrophic cardiomyopathy (AHCM or ApHCM), also called Yamaguchi syndrome. It was first described in individuals of Japanese descent. Sakamoto was the first to report the condition's ECG pattern in 1976. Yamaguchi was the first to characterize the syndrome and its ventriculargrophic feature in 1979.Yamaguchi H, Ishimura T, Nishiyama S, Nagasaki F, Nakanishi S, Takatsu F, Nishijo T, Umeda T, Machii K. Hypertrophic nonobstructive cardiomyopathy with giant negative T waves (apical hypertrophy): ventriculographic and echocardiographic features in 30 patients. Am J Cardiol. 1979 Sep;44(3):401-12. doi: 10.1016/0002-9149(79)90388-6. PMID 573056. Yamaguchi syndrome is an infrequent variant of hypertrophic cardiomyopathy in the European population. ApHCM is thought to be autosomal dominant, with the majority of mutations occurring in the genes encoding for the sarcomere. ECG findings in Yamaguchi syndrome may mimic those of a heart attack. Yamaguchi syndrome has a more favorable prognosis than classic hypertrophic cardiomyopathy, and it is more common in Asian populations.
Cardiac catheterization