Defined as myocardial hypertrophy in the absence of another cause.
It is characterized by hypertrophy of any portion of the left ventricular wall.
It frequently involves the basal interventricular septum, and HCM is not explained by abnormal loading conditions or myocardial infiltration.
Has significant genotypic, phenotypic and clinical heterogeneity.
Among the leading causes of identifiable sudden cardiac death in the young.
The most common inherited cardiac disease in the general population.
It has an estimated prevalence between one in 200 and one in 500 persons, with varying phenotypic characteristics.
Autosomal dominant process with hypertrophy of the left ventricle and sometimes the right, and often with predominate involvement of the intraventricular septum.
HCM occurs in both sexes, among all races, and in all age groups.
Dynamic left ventricular outflow track obstruction is present in approximately 50 to 70% of patients and causes lifestyle limiting symptoms.
The obstruction is dynamic and varies inversely with left ventricular volume, and increases when the patient is upright, and with the strain of a Valsalva maneuver, exercise, and the administration of inotropic agents.
The obstruction is usually caused by a combination of an hypertrophy, basal ventricular septum, and the systolic interior motion of the anterior leaflet of the mitral valve.
Some patients present with left ventricular outflow tract obstruction without septal hypertrophy, but with mitral valve or papillary muscle abnormalities.
Diastolic dysfunction is caused by slow filling of the thickened, fibrotic left ventricle which may result in enlargement of the left atrium and elevation of the left ventricular and diastolic, pulmonary capillary wedge and pulmonary arterial pressures.
Patients with HC M may be asymptomatic, experience fatigue, exertional dyspnea, angina, arrhythmias, syncope, heart failure, or have sudden cardiac death.
Angina may be be caused by increased oxygen requirements of the hypertrophied dysfunctional ventricle, the reduced lumina of the thickened walled intramural coronary arteries, and in myocardial fibrosis.
Affects men and women equally, and is present in persons of diverse ethnic backgrounds.
The left ventricular outflow tract obstruction is present or develops over time in 70% of patients with hypertrophic cardio myopathy.
The left ventricular cavity is usually small with increased contractility and abnormally elevated ejection fraction.
Histological findings include myocytes that are enlarged and in disarray and the presence of interstitial fibrosis and thick walled intramural coronary arteries.
One of the major determinant of exercise intolerance and limiting symptoms among patients with HCM is an elevated intracardiac pressure that results from left ventricular outflow tract obstruction.
Hypertrophy or displacement of the papillary muscles, anomalous insertion of the papillary muscles, and elongation of the mitral valve leaflets with systolic anterior motion and posterior directed mitral regurgitation are common ECHO features.
It is characterized by a thickened, non-dilated left ventricle, and is associated with exertional dyspnea, reduced exercise capacity, all of which can impair the quality of life.
The left ventricular outflow tract obstruction results from contact of the mitral valve with the ventricular septumduring systole is the one of the principal determinants of HCM related complications.
Caused by mutations in suPAR or Eric proteins.
Cardiac hypercontractility results from excessive numbers of actin-myosin cross bridges within the cardiac sarcomere.
Additionally, elongation of the mitral valve leaflets, apical displacement of the papillary. muscles and protrusion of the hypertrophied ventricular septum into the left ventricular outflow tract promote outflow obstruction.
The impedance to blood flow generates a left ventricular outflow tract pressure gradient, which can be quantified by echocardiography.
HCM is often a genetic disease of autosomal dominant inheritance.
Associated with more than 1000 mutations in 11 genes.
Most variance in code components of the sarcomere.
Genetic tests are negative and approximately 50% of all unrelated patients with HCM.
Gene abnormalities encode components of the contractile apparatus of heart muscle and the genes encoding sarcomeric proteins cause hypertrophic cardiomyopathy.
Prevalence of 1 per 200-500 in the U.S. population and higher in blacks.
Can affect individuals of all ages.
Inheriteded primarily as an autosomal dominant, although sporadic mutations occur.
Significant proportion of cases occur in a familial pattern.
Mutations in any one of the genes involved are found in up to two thirds of patients with hypertrophic cardiomyopathy.
Familial hypertrophic cardiomyopathy inherited as an autosomal dominant pattern.
Doppler velocities of the mitral annulus correlate with global systolic and diastolic left ventricular performance and can predict prehypertrophy sarcomere dysfunction.
Hallmark features Includes myocyte fibrosis and disarray.
Myocardial fibrosis is a prominent pathophysiologic component of this complex genetic disease, related to the risk of sudden death and heart failure.
Many cases associated with a mutation in the genes that codes for the proteins of the cardiac sarcomere.
At present, pathogenic variants in at least eight genes encoding sarcomeric proteins and are considered cause of HCM.
Mutations in MYH7, encoding the β -myosin heavy chain, and in MYBPC3, encoding cardiac myosin-biding protein are the most common, with each accounting for one quarter to one third of all cases of the disease, and the remaining genes each account for less than 1-5% of cases (Richard P et al).
Beta-myosin heavy chain mutations provide the pathogenic basis of this disease with disease of the myofilament.
Pathogenic variants modify, encoded sarcomeric proteins, and may alter the calcium sensitivity actomyosin control mechanisms, energy metabolism, and mitochondrial function of cardiomyocytes.
Patients with clinical or functional changes of HCM are said to be phenotype positive.
Gene positive HCM is seen in approximately 40% of patients.
Owing to the variability of genetic penetration and genetic expressivity, not all patients who are gene positive are phenotype positive.
Patients who are gene positive and phenotype positive have more serious clinical manifestations, with earlier onset of disease, more frequent arrhythmias and heart failure than persons who are gene negative and phenotype positive.
In gene positive patients, the most frequent pathogenic variants are detected with the use of multigenic panels in the gene that encode beta myosin binding protein, and the beta myosin heavy chain which are present in approximately 45 and 35%, respectively of people who are gene positive.
A family history, genetic testing should be conducted with the use of multigenic panels in person who are gene positive, and this holds for family members.
Myocyte dysfunction precedes hypertrophy.
Left ventricular replacement fibrosis and scarring has been implicated in triggering life-threatening arrhythmias, ventricular fibrillation and a marker for sudden death.
Heterogenous disorder associated with myofibril disarray and asymmetric myocardial hypertrophy of the ventricular septum or apex.
Mitral valve incompetence is almost invariably present with left ventricular outflow obstruction.
Congestive heart failure is 5 times more likely than in an unaffected population.
With the development of ICD‘s, the resultant reduction in the incidence of sudden cardiac death, heart failure has become an increasing concern.
Excessive sarcomeric contractility is reflected in a super normal LVEF, often 70 to 75%.
A LVEF of less than 50% in patients with HCM represents serious left ventricular dysfunction comparable to LVEF of 35 to 40% in patients with systolic heart failure without HCM.
Most patients have left ventricular outlet tract obstruction (LVOT), which is typically due to systolic anterior motion of the mitral valve leaflets.
Most patients are asymptomatic.
LVOT obstruction may occur at rest or be latent being manifest, by activity.
Most common monogenic heart disorder and cause of death from cardiac causes in children and adolescents.
If pressure gradients of >30 mm Hg are present at rest, the potential for further hypertrophy and deterioration is highly likely.
Ventricular arrhythmias may precipitate sudden death.
Most common cause of sudden death in young people.
Symptoms can be caused by diastolic dysfunction, mitral regurgitation and myocardial ischemia.
Diagnostic suspicion related to symptoms, physical exam findings, family history, or LVH on EKG,
Symptoms include:dyspnea on exertion, dizziness, presyncope, syncope, anginal or non-anginal chest pains, and palpitations.
Clinical exam findings include sustained LV impulse, sytolic murmur, S4 sound, bifid carotid carotid upstroke and spike and dome arterial pulse.
EKG demonstrates giant negative T waves associated with high QRS voltage in the lateral precordial leads despite the absence of hypertension and coronary artery disease.
Coronary artery disease is present in up to 20% of patients with hypertrophic cardio myopathy and severe coronary disease is associated with disproportionately increased risk of death in hypertrophic cardiomyopathy.
Relationship between the depth of inverted T waves and the apex/midwall thickness ratio suggest that the abnormal repolarization of the hypertrophied apical musculature causes these giant T wave inversions.
Systolic murmur due to LVOT obstruction and or mitral regurgitation, usually at the left sternal border.
The murmur of obstructive hypertrophic cardiomyopathy increases with decreased preload or decreased after load and it decreases on the opposite conditions.
The murmur of obstructive hypertrophic cardiomyopathy increases with squat to stand and Valsalva maneuvers and decreases with stand to squat or handgrip maneuvers.
Late gadolinium enhancement may identify patients who can benefit from a primary prevention of sudden death with implantable cardioverter-defibrillators, or who evolve to the end stage of this disease with systolic dysfunction and consideration for heart transplant.
Primary prevention with an ICD use risk markers, including a family history of sudden cardiac death, left ventricular wall thickness of at least 30 mm, left ventricular apical aneurysm, unexplained syncope, multiple prolonged episodes of non-sustained ventricular tachycardia, extensive late gadolinium enhancement, and left ventricular ejection fraction of less than 50%.
The application of ICD’s in patients with HCM, who are high risk reduced the incidence of sudden cardiac death in the population to less than 0.5% per year.
Treatment:
Treatment guidelines dichotomized symptom management on the basis of the presence or absence of left ventricular outflow tract obstruction.
For patients with obstruction first line pharmacologic agents, including beta blockers or non-dihydropyridine calcium channel blockers are used.
Patients with obstructive HCM and refractory symptoms could be also treated with disopyramide or septal reduction therapies such as surgical myomectomy or alcohol septal ablation.
Pharmacologic myosin inhibitors are additional treatment options.
Mavacamten and and aficamten improve left ventricular outflow tract gradients, peak oxygen update, and decrease symptoms.
In HCM without a left ventricular outflow tract obstruction there is high symptom burden, and fewer treatment options:myosin inhibitors are not effective and may increase adverse events.
Invasive therapies for obstructive HCM include surgical myectomy and percutaneous alcohol septal ablation are effective in relieving left ventricular outflow tract gradients and favorably affect the clinical course and relief of symptoms.
Surgical mortality ranges from <2% to 5% for myectomy.
In elderly patients diagnosed in the fifth or sixth decades of life have a morphological subtype of disease characterized as a sigmoid ventricular septum compared with patients diagnosed at a young age.
Older populations of patients have fewer symptoms and fewer sudden deaths.
Beta-myosin heavy chain mutations provide the pathogenic basis of this disease with disease of the myofilament.
Myocyte dysfunction precedes hypertrophy.
Heterogenous disorder associated with myofibril disarray and asymmetric myocardial hypertrophy of the ventricular septum or apex.
Mitral valve incompetence is almost invariably present with left ventricular outflow obstruction.
Congestive heart failure is 5 times more likely than in an unaffected population.
Most patients have left ventricular outlet tract obstruction (LVOT), which is typically due to systolic anterior motion of the mitral valve leaflets.
LVOT obstruction may occur at rest or be latent being manifest, by activity.
Most common monogenic heart disorder and cause of death from cardiac causes in children and adolescents.
If pressure gradients of >30 mm Hg are present at rest, the potential for further hypertrophy and deterioration is highly likely.
Ventricular arrhythmias may precipitate sudden death.
Most common cause of sudden death in young people.
Symptoms can be caused by diadtolic dysfunction, mitral regurgitation and myocardial ischemia.
Diagnostic suspicion related to symptoms, physical exam findings, family history, or LVH on EKG,
Symptoms include:dyspnea on exertion, dizziness, presyncope, syncope, anginal or non-anginal chest pains, and palpitations.
Clinical exam findings include sustained LV impulse, sytolic murmur, S4 sound, bifid carotid carotid upstroke and spike and dome arterial pulse.
Systolic murmur due to LVOT obstruction and or mitral regurgitation, usually at the left sternal border.
Transthoracic echocardiogram findings in hypertrophic cardiomyopathy include asymmetric LVH, an LV wall thickness of a 15 mm or greater in patients without another cardiac or systemic causes and left ventricular outflow tract obstruction on Doppler ultrasound.
Echocardiography is usually decisive for screening and for establishing or excluding the diagnosis.
Cardiac MRI provides greatest spatial resolution than echocardiography, and is regarded as the standard for non-invasive imaging.
Cardiac MRI can detect the presence and extent of late gadolinium enhancement and provides more accurate measurement of ventricular wall and interventricular, septal thickness, variables that help in the assessment of the risk of sudden cardiac death.
cardiac CT can determine the presence or absence of obstructive epicardial, coronary artery disease and myocardial bridging, can provide accurate ventricular volumes, ventricular wall thickness, ejection fraction, and fibrosis evaluation in patients with contraindications to cardiac MRI.
Asymmetric LVH is most commonly associated with hypertrophic cardiomyopathy, however symmetrical LVH does not exclude the diagnosis.
Surgical mortality ranges from <2% to 5% for myectomy.
Transaortic septal myectomy has been the initial therapy for this type procedure, removing obstructive segments of the interventricular septum, reducing mitral regurgitation.
This procedure permits, the addition of other techniques, including coronary artery bypass, and the Maze procedure inpatient with atrial fibrillation.
Nonsurgical myocardial reduction with dessicated alcohol infused into the first major septal perforator of the left anterior descending coronary artery associated with a hospital mortality between 0 and 4%.
Alcohol septal ablation as a higher rate of causing complete heart block than transaortic myectomy myectomy, but it has a much shorter recovery time.
Septal reduction therapy is considered in patients with obstructive HCM NYHA classes III or IV despite first line therapy and treatment with a cardiac myosin inhibitor.
For both septal reduction techniques the 30 day mortality is 0.4%, and an annual mortality of 0.6% and an incidence of heart failure of 1.9%.
In elderly patients diagnosed in the fifth or sixth decades of life have a morphological subtype of disease characterized as a sigmoid ventricular septum compared with patients diagnosed at a young age.
Older populations of patients have fewer symptoms and fewer sudden deaths.
Apical hypertrophic cardiomyopathy, also known as Yamaguchi syndrome, is a variant of hypertrophic cardiomyopathy and is relatively common in Japan.
Apical hypertrophic cardiomyopathy is rare in non-Japanese populations.
Apical hypertrophic cardiomyopathy predominately involves the apex of the left ventricle without the typical septal predominance seen hypertrophic obstructive cardiomyopathy.
Apical hypertrophic cardiomyopathy, in the absence of left ventricular outflow tract obstruction, most patients do not have a heart murmur.
Apical hypertrophic cardiomyopathy prognosis is relatively benign with a follow up with 13 1/2 years, all cause mortality 10.5% and cardiovascular mortality 1.9% (Eriksson MJ et al).
There is a pure apical form and a distal dominant form of apical hypertrophic cardiomyopathy.
With the distal dominant form of apical hypertrophic cardiomyopathy patients are more symptomatic and more likely to experience cardiovascular events.
Apical hypertrophic cardiomyopathy may be associated atrial fibrillation, myocardial infarction, apical aneurysm, ventricular arrhythmias, and sudden cardiac death.
Majority of patients with apical hypertrophic myopathy have maintained functional status, and approximately half are asymptomatic on follow up.