Hypertrophic cardiomyopathy

Overview

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant condition that alters the structure of the heart, affecting its function. Hypertrophy of the left ventricle produces left ventricular outflow blockage, diastolic dysfunction, myocardial ischemia, and mitral regurgitation.

Fatigue, dyspnea, chest discomfort, palpitations, and syncope might result. Sudden cardiac death is the most severe and deadly manifestation of HCM, and it is most commonly found in young athletes.

Hypertrophic cardiomyopathy definition

Hypertrophic cardiomyopathy (HCM) is a complicated kind of cardiac disease affecting the heart muscle. It causes heart muscle thickening (particularly in the ventricles, or lower heart chambers), left ventricular stiffness, mitral valve alterations, and cellular changes.

HCM is a hereditary (autosomal dominant) heart muscle disorder caused by a mutation in sarcomere protein genes, which encode parts of the heart's contractile mechanism. It is distinguished by an increase in the thickness of the left ventricular wall (hypertrophy), which results in left ventricular outflow blockage, diastolic dysfunction, myocardial ischemia, and mitral regurgitation.

Epidemiology

According to echocardiographic studies, the incidence of HCM in the general population worldwide is 0.2 percent (1 in 500 individuals). Morphologic evidence is discovered in roughly 25% of first-degree relatives of HCM patients. Newer genetic testing has been established that can be used to identify asymptomatic family members who share the same sarcomere mutation.

HCM is more frequent in men than in women; however, because the illness is autosomal dominant, genetic inheritance does not follow gender. The most typical age of onset is in the third decade of life, but it can occur at any age, from infants to the elderly.

HCM has a bimodal peak of incidence in general. The most typical age of onset is in the third decade of life, but it can occur at any age, from infants to the elderly.

In children, hereditary instances are seen from birth (ie, stillborn infants) until adulthood. In many circumstances, the highest incidence occurs in the second decade of life. The peak incidence in adults occurs in the third decade of life, with the great majority of cases occurring between the third and sixth decades of life.

Etiology

In roughly 50% of cases, familial hypertrophic cardiomyopathy is an autosomal dominant Mendelian-Inherited disease. A mutation in the sarcomere protein gene, which codes for contractile components of the heart, has been discovered, and 6 separate genes on at least 4 chromosomes have been linked to HCM. Over 50 distinct mutations have been discovered.

Abnormal calcium kinetics

Data show that aberrant myocardial calcium kinetics are the source of inappropriate cardiac enlargement and specific aspects of HCM, especially in individuals with diastolic functional problems. Aberrant cardiac calcium kinetics and abnormal calcium fluxes caused by an increase in the number of calcium channels result in a rise in intracellular calcium concentration, which may result in hypertrophy and cellular disarray.

Genetic causes

In roughly 50% of instances, familial HCM is an autosomal dominant Mendelian-inherited illness. Spontaneous mutations may be responsible for some, if not all, of the sporadic forms of the illness. HCM is linked to at least six distinct genes on at least four chromosomes, with more than 50 different mutations found thus far. Familial HCM is a genetically heterogeneous illness, meaning that it can be caused by genetic abnormalities at several loci.

Seidman and colleagues were the first to reveal the genetic basis for HCM in 1989. They discovered the presence of a disease gene on the long arm of chromosome 14. They later discovered that this was the gene encoding the beta cardiac myosin heavy chain.

The phenotypic manifestation of a specific mutation of a given gene varies greatly, as do clinical symptoms and the degree of hypertrophy displayed. Distinct mutations are connected with specific symptoms, the degree of hypertrophy, and the prognosis, with phenotypic variability due to genotype variations.

Other possible causes

Other possible causes of HCM include the following:

Abnormal sympathetic stimulation - HCM may be caused by the heart's increased reactivity to excessive catecholamine synthesis or decreased neuronal absorption of norepinephrine.
Intramural coronary arteries that are abnormally thickened - These do not dilate properly, resulting in myocardial ischemia; this proceeds to myocardial fibrosis and aberrant compensatory hypertrophy.
Subendocardial ischemia is caused by anomalies in the cardiac microcirculation that deplete the energy supplies required for calcium sequestration during diastole; subendocardial ischemia causes continuous interaction of the contractile components throughout diastole and increased diastolic stiffness.
Cardiac structural abnormalities include a catenoid septum shape, which causes myocardial cell enlargement and disarray.

Pathophysiology

Ventricular hypertrophy causes a dynamic pressure gradient across the left ventricular outflow tract (LVOT), resulting in additional constriction during systole. Several postulated processes drive the mitral valve towards the septum during the cardiac cycle: contraction of the papillary muscles, aberrant position in the outflow tract, and low pressure caused by blood expelled at high velocity via a narrower outflow tract (Venturi effect).

Hypertrophic cardiomyopathy symptoms

Dyspnea is the most prevalent symptom of hypertrophic cardiomyopathy. Syncope, palpitations, angina, orthopnea, paroxysmal nocturnal dyspnea, disorientation, congestive heart failure, and sudden cardiac death can also occur in patients. The latter is the most dangerous presenting sign.

Despite the existence of heart enlargement, people with HCM are frequently asymptomatic or have very minor symptoms. The most common symptoms are caused by four basic pathophysiologic conditions: diastolic ventricular dysfunction, restriction to left ventricular outflow, myocardial oxygen supply and demand imbalance, and cardiac arrhythmias.

Diastolic Dysfunction

As a result of this prevalent pathophysiologic expression in HCM (see above), the left ventricular end diastolic pressure rises, causing the left atrial, pulmonary venous, and pulmonary capillary pressures to rise as well. Exertion causes a significant rise in left ventricular diastolic pressure, resulting in exertional dyspnea, exercise intolerance, orthopnea, peripheral edema, and HFpEF.

LVOT Obstruction

At rest, approximately one-third of HCM patients develop LVOT, which is exacerbated by exercise. One-third have provokable obstruction (see below), whereas the other third have left ventricular hypertrophy without blockage at rest that is not provokable. Patients with severe blockage typically have increased ventricular diastolic pressure and exertional dyspnea, and some develop outright heart failure. Exertional or post-exercise syncope can be caused by significant blockage, with or without ventricular arrhythmia.

Chest pain

Patients with HCM frequently feel ischemic chest discomfort, which may or may not resemble angina pectoris. This symptom is caused by an imbalance in myocardial oxygen supply and demand. Myocardial hypoperfusion occurs as a result of decreased blood flow through the aforementioned thick-walled, intramural coronary arteries with luminal constriction and increased oxygen demand of the hypertrophied myocardium.

Arrhythmias

Palpitations, pre-syncope, and syncope are among the most common clinical symptoms, which are generally caused by repeated non-sustained ventricular tachycardia. Supra-ventricular and ventricular ectopic beats are rather common, and non-sustained ventricular tachycardia (NSVT) is found in 20 to 30% of individuals. NSVT is a key risk factor for SCD because such episodes can develop to ventricular fibrillation, which is the most common cause of SCD.

Severe LVOT blockage can also induce syncope. The processes driving ventricular arrhythmias in HCM are mainly unclear. Potential processes include ventricular remodeling due to cardiac hypertrophy, interstitial fibrosis, myocardial ischemia, and myocyte disarray.

Atrial fibrillation affects around a quarter of individuals with HCM with LVOT blockage, with an annual incidence of 2 to 3%. This arrhythmia is poorly tolerated because the lack of atrial contribution to ventricular filling, along with the high ventricular rate, results in subsequent elevations in left ventricular diastolic pressure and symptoms of heart failure. It's also a significant risk factor for thromboembolic stroke.

The size and function of the left atrium, as well as LVOT blockage, are key risk factors for atrial fibrillation. The mechanism(s) underlying atrial fibrillation in HCM have not been identified. Potential causes include diastolic dysfunction-induced atrial expansion and strain, atrial fibrosis, mutant protein expression, and altered gene expression.

Physical findings may include the following:

Double apical impulse or triple apical impulse (less common)
Normal first heart sound; second heart sound usually is normally split but is paradoxically split in some patients with severe outflow gradients; S3 gallop is common in children but signifies decompensated CHF in adults; S4 is frequently heard
Jugular venous pulse revealing a prominent a wave
Double carotid arterial pulse
Apical precordial impulse that is displaced laterally and usually is abnormally forceful and enlarged
Systolic ejection crescendo-decrescendo murmur
Holosystolic murmur at the apex and axilla of mitral regurgitation
A diastolic decrescendo murmur of aortic regurgitation (10% of patients)

A systolic ejection murmur is present in the following ways: decreased intensity with increasing preload (squatting) or afterload (handgrip), increased intensity with decreasing preload (Valsalva maneuver, standing), and any reduction in afterload (vasodilator administration).

Diagnosis

All patients should have a comprehensive cardiac history and physical examination. An electrocardiogram (ECG) and cardiac imaging to identify left ventricular hypertrophy should be performed in all patients.

ECG: the most accurate diagnostic test Localized or extensive repolarization alterations, significant Q waves in the inferior (II, III, and aVF) and lateral leads (I, aVL, and V4-V6), left atrial or biatrial hypertrophy, left axis deviation, and profoundly inverted T waves are all seen. The presence of both left ventricular hypertrophy (LVH) and right atrial enlargement strongly suggests HCM.
Transthoracic echocardiogram (TTE): Cardiac morphology, systolic and diastolic function, the existence and severity of any LVOT gradient, and the degree of mitral regurgitation are all demonstrated.
Ambulatory ECG monitoring: Should be performed for 24 to 48 hours in all patients diagnosed with HCM for risk assessment of ventricular arrhythmias and sudden death.
Exercise stress testing: For risk stratification and assessment of LV outflow tract (LVOT) gradient. Exercise stress is the preferred method.

Some patients may also require the following:

Cardiac catheterization: Determines cardiac hemodynamics, the degree of left ventricular outflow blockage, and coronary artery architecture.
Electrophysiological studies: Determine the origin of the arrhythmias.

Other imaging modalities that may be useful include the following:

Chest radiography
Radionuclide imaging
Cardiac magnetic resonance imaging: Particularly useful when echocardiography is questionable, particularly with apical hypertrophy

Electrocardiographic findings may include the following:

ST-T wave abnormalities and LVH (common)
Axis deviation (right or left)
Conduction abnormalities (P-R prolongation, bundle-branch block)
Sinus bradycardia with ectopic atrial rhythm
Atrial enlargement
Atypical and pronounced Q wave in the anterior precordial and lateral limb leads, a short P-R interval with QRS indicative of preexcitation, atrial fibrillation (bad prognosis), and a P-wave anomaly (all uncommon)

The following diagnostic modalities may also be useful:

Cardiac catheterization (to determine the degree of outflow obstruction, cardiac hemodynamics, the anatomy and diastolic characteristics of the left ventricle, and the coronary anatomy)
Electrophysiologic studies

Treatment for hypertrophic cardiomyopathy

Because no major randomized studies have been conducted, treatment methods for HCM are based on observational data and clinical experience. The first-line treatment for symptomatic HCH is pharmacological therapy. Negative inotropic medicines such as beta blockers, nondihydropyridine calcium channel blockers (verapamil), and disopyramide are the best first-line treatments.

Diuretics can be administered to individuals with volume overload who do not have LVOT blockage or refractory heart failure symptoms. Depletion of volume reduces stroke volume and worsens the LVOT gradient. This can result in hypotension, dizziness, and syncope.
Nonpharmacologic options include surgical myomectomy and alcohol septal ablation (if the NYHA III/IV class persists after appropriate medical therapy or syncope due to hemodynamic impairment from LVOT blockage, with an LVOT gradient greater than 50mmHg)
Alcohol septal ablation relieves symptoms, boosts exercise capacity, and may improve long-term survival by reducing LVOT blockage.

Surgical therapeutic options include the following:

A heart transplant is not the first treatment option and usually recommended only in patients who have failed all medical and surgical treatments.
Left ventricular myomectomy
Mitral valve replacement
Permanent pacemaker implantation
Placement of an implantable cardioverter defibrillator is an option in patients with ventricular fibrillation who do not want lifelong medical therapy.

Differential Diagnosis

Aortic stenosis
Athlete’s heart
Amyloidosis
Genetics of Fabry disease
Glycogen storage disease
Hypertensive heart disease
Mucopolysaccharide storage disease
Right ventricular hypertrophy
Restrictive cardiomyopathy
Sarcoidosis

Prognosis

Annual death rates in people with hypertrophic cardiomyopathy (HCM) have been reported to range from less than 1% to 3-6%, and studies indicate that they have greatly improved over the last 40 years.

According to a 2006 research, documented sudden death rates during the preceding ten years were lower than previously released statistics (median 1.0 percent ). Nonetheless, HCM is associated with a substantial risk of death and morbidity.

One study of 46 individuals indicated that those with midventricular blockage had an increased risk of apical aneurysm development, symptoms, and HCM-related mortality compared to those without; the increased risk of symptoms and death was comparable to that identified in patients with LV outflow obstruction.

The majority of HCM patients are asymptomatic. Unfortunately, in such cases, the initial clinical indication of the condition may be sudden death, most commonly due to ventricular tachycardia or fibrillation. Younger patients, particularly children, die at a substantially greater rate. Children have substantially higher ventricular hypertrophy and are much more symptomatic early in the illness course, most likely due to the presence of more malignant genotypes earlier in life.

In the pediatric population, the more benign mutations do not cause a clinical or echocardiographic phenotype or symptoms. Death is frequently abrupt and unexpected, and it is frequently related with sports or strenuous exercise. Early diagnosis is critical for prescribing an adequate degree of safe exercise.

Screening first-degree relatives can help detect further afflicted family members before major symptoms or abrupt death.

Arrhythmias such as atrial fibrillation, atrial flutter, ventricular ectopy, ventricular tachycardia, and ventricular fibrillation can occur in patients. These patients are among the most vulnerable to ventricular fibrillation and provide complex treatment options for risk reduction.

Patients are at significant risk of recurrent heart failure as a result of mitral regurgitation and severe diastolic dysfunction. If left untreated, HCM is a degenerative disorder that increases with time, as does the gradient throughout the LV outflow tract. Until the late stages of the illness, systolic function is typically adequately preserved. Angina is uncommon in children but prevalent in adults. Syncope and presyncope are widespread and can identify those who are at high risk of dying suddenly.

Conclusion

Hypertrophic cardiomyopathy (HCM) is a hereditary condition characterized by unexplained left ventricular hypertrophy and a nondilated left ventricle with preserved or increasing ejection fraction. The most extreme hypertrophy affects the basal interventricular septum and is usually asymmetrical. One-third of individuals have left ventricular outflow tract blockage at rest, and another third can be induced.

Myocyte enlargement and disarray, as well as interstitial fibrosis, are histological hallmarks of HCM. Hypertrophy is commonly related with diastolic dysfunction of the left ventricle. HCM has a very benign course in the vast majority of individuals.

Patients with hypertrophic cardiomyopathy are diagnosed and managed by an interprofessional team that includes a cardiologist, cardiac surgeon, electrophysiologist, internist, primary care provider, and nurse practitioner. The disease can be treated in a variety of ways. Some people may benefit from surgery in addition to pharmacological treatment.

Mitral valve replacement, left ventricular myomectomy, pacemaker or AICD installation, or heart transplant are among surgical alternatives. These patients' results are favorable as long as they comply with therapy. Unfortunately, many people continue to develop atrial and ventricular arrhythmias even after therapy. Sudden death may be the initial sign for people who are untreated.