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The Cardiomyopathies

The Cardiomyopathies

Definition: Cardiomyopathy is a disease of the heart muscle (myocardium) causing structural and functional abnormalities, which does not result from coronary artery disease, hypertension, valvular disease, or congenital heart disease.
The term "ischemic cardiomyopathy" continues to be in use for left ventricular systolic dysfunction caused by myocardial scar and left ventricular remodeling after myocardial infarction, although according to this definition it is not exactly a cardiomyopathy, but a secondary myocardial disease.
Most (but not all) cardiomyopathies are familial. Thus family screening is often mandatory to identify people with undiagnosed or subclinical disease. In familial cardiomyopathies, the inheritance is most often autosomal dominant and less often X- linked recessive, or autosomal recessive.
Cardiomyopathies are a heterogeneous group of diseases. Recently the MOGES classification system has been adopted, which describes the morphological and functional (morphofunctional) phenotype (M), organ involvement (O), genetic inheritance pattern (G), etiology (E), functional status (S).
Another classification of cardiomyopathies includes primary cardiomyopathies characterized by disease involving predominantly the myocardium and secondary cardiomyopathies, i.e. myocardial disease associated with a known specific etiology.
Primary cardiomyopathies include: 
Cardiomyopathies of genetic etiology
Hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, myocardial noncompaction, glycogen storage disease (such as Danon's disease), mitochondrial myopathies and genetic ion channel disorders (channelopathies such as Brugada syndrome, congenital long QT syndrome, congenital short QT syndrome, catecholaminergic polymorphic ventricular tachycardia).
Cardiomyopathies of mixed (genetic or acquired) etiology:
 This category includes dilated cardiomyopathy and restrictive cardiomyopathy
Acquired cardiomyopathies such as:
 inflammatory cardiomyopathy (caused by myocarditis), alcoholic cardiomyopathy, peripartum cardiomyopathy, tachycardiomyopathy (cardiomyopathy due to a persistent tachyarrhythmia), stress-induced cardiomyopathy also known as Tako-tsubo cardiomyopathy, cardiac sarcoidosis.


Hypertrophic cardiomyopathy (HCM) 
It is the most common inherited cardiac disorder with a prevalence in the general population of approximately 1 per 500. 

There is hypertrophy of left (usually), right, or both ventricles
with 
preserved or reduced contractile function. Hypertrophy (increased cardiac muscle thickness) is inappropriate (is not expected as a result of an etiologic condition, such as hypertension, aortic stenosis, etc) may be generalized or regional and it almost always presents by the age of 30 years. Histologically HCM is characterized by left ventricular hypertrophy with malalignment of the myocardial fibers (myofibril disarray) and myocardial fibrosis. The hypertrophy may be generalized or confined largely to the interventricular septum (asymmetric septal hypertrophy) or other regions (e.g. apical hypertrophic cardiomyopathy).
Causes of HCM
HCM is a genetic disorder, caused by mutations of genes encoding proteins involved in the contractile apparatus of the myocardial cells. The most common mutation involves beta-myosin heavy chains. There are also other mutations involving troponin T, tropomyosin, and other proteins. The mode of genetic transmission is usually autosomal dominant, with a high degree of penetrance and variable expression.
Clinical presentation: most patients with HCM are asymptomatic, but some present with dyspnea, effort angina palpitations (due to arrhythmias), syncope, or sudden death. In summary, hypertrophic cardiomyopathy (HCM) can be asymptomatic or it can result in heart failure with preserved ejection fraction (EF), in sudden cardiac death, or rarely in heart failure with reduced EF.
 Heart failure with preserved ejection fraction (EF), usually manifested by effort dyspnea (breathlessness during physical activity) can occur in HCM because myocardial hypertrophy can produce a stiff ventricle with reduced compliance. This results in an elevation of the diastolic filling pressure. 
Angina, when present, in HCM usually results from increased myocardial oxygen demand due to the hypertrophy.
In hypertrophic obstructive cardiomyopathy (HOCM), a form of HCM characterized by the presence of dynamic left ventricular outflow tract (LVOT) obstruction, the systolic pressure gradient in the LVOT contributes to the development of symptoms.  In HOCM the dynamic LVOT obstruction is caused by the hypertrophy of the interventricular septum and the abnormal systolic anterior motion (SAM) of the mitral valve. SAM can also cause mitral regurgitation.
Physical examination in HCM can be normal or reveal only a fourth (presystolic) heart sound S4 when there is no LVOT obstruction. The S4 is caused by LV diastolic dysfunction resulting in a forceful left atrial contraction against a stiff ventricle. The apical impulse is often forceful and diffuse. A double impulse can be present because of a presystolic impulse due to the forceful atrial contraction as a consequence of the reduced LV compliance.
In hypertrophic obstructive cardiomyopathy (HOCM) :
 >The carotid pulse typically rises sharply and then falls sharply in mid systole (because of the LVOT obstruction in mid systole) followed by a second rise
> There is a midsystolic crescendo-decrescendo murmur best heard at the left sternal border and at the area between the apex and the left sternal border. This murmur of dynamic LVOT obstruction is accentuated by maneuvers that decrease preload (abruptly standing up, which reduces venous return to the heart) or decrease afterload (vasodilation by administering sublingual nitrate) and does not radiate to the neck. These features help distinguish the murmur of HOCM from the murmur of valvular aortic stenosis (also see the chapter on aortic stenosis).
> A pansystolic murmur is often heard at the apex due to mitral regurgitation.
The ECG is abnormal in the majority of patients with hypertrophic cardiomyopathy (HCM). The commonest abnormalities are ST and T wave abnormalities followed by signs of left ventricular hypertrophy ( Tall R waves especially in mid-precordial leads and also in left precordial leads). Prominent  Q waves may be present in the inferior and/or precordial leads, caused by septal hypertrophy. Giant negative T waves in the precordial leads occur in apical HCM. 
The chest X-ray may demonstrate a normal heart size or cardiac enlargement due to LV hypertrophy and left atrial dilatation. 
Echocardiography in HCM 
There are some characteristic features that strongly indicate HCM:
1) Hypertrophy of any segment of the LV with wall thickness > 1,5 cm.
2) Asymmetric septal hypertrophy (the interventricular septum is much thicker than other segments of LV wall) with a ratio of wall thickness septum/posterior wall > 1.3 in normotensive and > 1.5 in hypertensive individuals. This is the commonest form of HCM.
3) In HOCM (a common type of HCM): Asymmetric hypertrophy of the interventricular septum with SAM of the anterior mitral leaflet, increased velocity of flow in the left ventricular outflow tract (LVOT) and a systolic pressure gradient in the LVOT. The latter two findings are evidence of LV dynamic obstruction. Obstruction is dynamic, meaning that it changes at different times at the same patient and especially with changes in preload, afterload or contractility. Some patients have an obstruction at rest, whereas others only during exercise.  Obstruction is present when the peak intraventricular systolic gradient is ≥ 30 mmHg. Severe obstruction is present when the peak gradient is > 50 mmHg.   Mitral regurgitation is often present. 
4) Concentric hypertrophy of the LV without any identifiable cause, especially with a wall thickness ≥ 1.5 cm.
5) Apical hypertrophy of the LV (this is a rare form of HCM, about 1 % of cases)
6) Mid-ventricular hypertrophy of the LV with signs of systolic obstruction at the level of the papillary muscles (such signs are a turbulent high-velocity systolic flow at the midventricular level, demonstrated with color flow doppler and a systolic intraventricular gradient at this level, demonstrated with pulse wave spectral doppler.) The LV apex is usually aneurysmatic. This is a rare form of HCM.
7) In some cases of HCM hypertrophy of the right ventricle (RV) can also be present (RV wall thickness > 5 mm).
Differential diagnosis of HCM includes other causes of increased ventricular wall thickness: e.g. hypertensive heart disease, aortic stenosis, infiltrative and storage diseases (amyloidosis, Fabry disease).
Treatment of HCM
In patients without an LVOT gradient pharmacologic therapy is administered if there are symptoms (dyspnea or chest pain): Beta-blockers (starting at a dose equivalent to propranolol 80-120 mg/day and titrated to achieve a heart rate of 50-70 beats per minute at rest ) or alternatively nondihydropyridine calcium antagonists (verapamil starting at a dose of 120 mg/day, or diltiazem starting at a dose of 180 mg/day).

In patients with HOCM who have symptoms, treatment to reduce the LVOT gradient is indicated. Such treatment includes
beta-blockers, usually in high doses. If this fails, combined treatment with a beta-blocker (in a small to moderate dose) plus disopyramide  (an antiarrhythmic drug with potent negative inotropic properties) is an option. Disopyramide is usually given at a dose of 400-600 mg/day and can often cause side effects due to its anticholinergic action (dry mouth and eyes, urinary retention).
Surgical myectomy, alcohol septal ablation or DDD pacing are treatment options (that act by reducing the LVOT gradient) selected in cases of HOCM with symptoms refractory to medical therapy, or who cannot tolerate medical therapy and a significant LVOT pressure gradient (i.e. a pressure gradient > 50 mmHg in the LVOT, in LV systole). DDD pacing generally is less effective than the other two treatments (surgery, or septal ablation). Both surgical myectomy and alcohol septal ablation are effective procedures, associated with low rates of complications and high success rates when performed in centers with experience. There is a debate regarding which procedure is best. Two basic concerns with percutaneous septal ablation are the following: There is a potential for the creation of an arrhythmogenic focus (since the procedure causes a myocardial infarct at the proximal interventricular septum) and there is also an increased risk of complete heart block, as a procedural complication.
In summary, in HCM either with or without intraventricular obstruction, treatment is needed in patients who have symptoms and not in asymptomatic people. Evaluation of risk factors for sudden cardiac death is needed in all patients. 

Important: Risk factors for sudden death in HCM  are as follows:
The most powerful, but also very obvious, risk factor is a personal history of resuscitated cardiac arrest, or sustained ventricular tachycardia. This is an indication for an implantable defibrillator (ICD). 
Massive left ventricular hypertrophy (>30 mm on echocardiography)
Family history of sudden cardiac death (that has occured before the age of 50 in one or more first-degree relatives with or without a diagnosis of HCM, or sudden death in one or more first-degree relatives irrespective of age, with an established diagnosis of HCM).
Non-sustained ventricular tachycardia on 24-hour Holter monitoring
Prior unexplained syncope
Abnormal blood pressure (BP) response on exercise (failure of BP to rise, or a fall in BP with exercise).
 ICD insertion should be seriously considered in patients with 2 or more of these risk factors.  When the risk is less, amiodarone is an appropriate alternative.

A VIDEO :  Hypertrophic Cardiomyopathy: The ECG, echocardiography and treatment





Dilated cardiomyopathy (DCM):
There is impaired systolic function and dilatation of one or both ventricles. It more often affects the left ventricle and then it is characterized by left ventricular dilatation associated with decreased contractile function (left ventricular EF <45%) in the absence of coronary artery disease sufficient to cause global systolic dysfunction and in the absence of abnormal ventricular loading conditions (hypertension, valvular heart disease, congenital heart disease). DCM can result in heart failure with reduced ejection fraction (EF). Right ventricular dilation and dysfunction may also be present but are not necessary for the diagnosis.
Causes of DCM 
 The most common causes are idiopathic and inherited (familial DCM, due to genetic defects).
Idiopathic DCM includes cases with no clearly identified cause and is considered to result from an interplay of unclear familial, immune-mediated, toxic, or infectious mechanisms that ultimately result in myocardial systolic dysfunction. Some cases are due to a previous episode of subclinical viral myocarditis. Viral components present in the myocardial tissue may serve as antigens that can direct the immune system to attack the myocardium.
An abnormality of immune regulation may play a role in DCM, as suggested by the association of DCM with some HLA antigens (HLA DR4).
Familial DCM accounts for about 30-50 % of cases and is due to mutations of genes that result in myocardial dysfunction and reduced contractile force. Most cases of familial DCM demonstrate an autosomal dominant mode of inheritance, although autosomal recessive and X-linked forms also exist. They are the result of mutations of genes encoding cytoskeletal, contractile or nuclear membrane proteins (dystrophin, desmin, actin, troponin, a-tropomyosin, beta-myosin heavy chain, lamin, vinculin).  
Some neuromuscular diseases of genetic origin also cause DCM (Duchenne muscular dystrophy).

Other causes of DCM are due to myocardial inflammation and cell damage via infective, immunologic or toxic mechanisms.
Such causes are:
 Infections (viral myocarditis, Chagas disease)
Drugs and toxins (
Alcohol, cocaine, doxorubicin, cyclophosphamide,)
Peripartum cardiomyopathy
Systemic vasculitis (systemic lupus erythematosus)
Other causes of DCM include various systemic diseases such as uremia, thyroid disease, pheochromocytoma, glycogen storage disease.
Whereas coronary artery disease (CAD) is the most common cause of left ventricular (LV) systolic dysfunction and dilatation, this condition (often called ischemic cardiomyopathy) is not classified as dilated cardiomyopathy.
Clinical presentation of DCM 
DCM usually presents with signs and symptoms of congestive heart failure. Thus the major presenting symptoms are effort dyspnea or paroxysmal nocturnal dyspnea, fatigue and effort intolerance and edema. Other presentations include systemic emboli (from LV wall thrombus), syncope, angina, cardiac arrhythmias, conduction defects or sudden death (from ventricular arrhythmias). Chest pain, including typical angina, may be present in some patients with DCM (even though it is not considered one of the main symptoms) and should not be used as a proof of coronary artery disease as the etiology of myocardial systolic dysfunction. It may indicate a more limited coronary vascular reserve in these patients, despite normal epicardial coronary arteries.
Physical examination in DCM can show:
An apical impulse which is laterally displaced, because of left ventricular (LV) enlargement.
 A narrow pulse pressure (this is a sign of a diminished stroke volume)
Pulsus alternans (in cases of severe LV dysfunction).
In auscultation a fourth (presystolic) heart sound (S4) is common and in case of decompensated heart failure, there is often a third (early diastolic) heart sound -S3. Systolic murmurs of mitral or tricuspid regurgitation are also common because dilated cardiomyopathy (DCM) is often associated with functional atrioventricular valve regurgitation.
The ECG in DCM often shows poor R wave progression (or even Q waves) in the precordial leads, because of myocardial fibrosis and P wave morphology indicative of left atrial dilatation. ST and T wave abnormalities frequently occur.
   Another common finding is an intraventricular conduction defect (for example a LBBB) causing an increased QRS duration. Atrial or ventricular arrhythmias are also common. 
The chest X-ray usually demonstrates a generalized enlargement of the cardiac silhouette due to the dilatation of the cardiac chambers (cardiomegaly= enlargement of the heart).
Echocardiography is valuable for the diagnosis since it can assess ventricular size and function. Usually, in DCM there is a diffuse reduction of LV contractility (hypokinesis) with LV dilation (often the best contracting LV segment is the basal posterior and /or the basal lateral). In ischemic cardiomyopathy, diffuse hypokinesis and LV dilatation can also be present, but there is akinesis and reduced thickness of the infarcted segments. This is a useful distinguishing feature between these two entities. 
In some cases of mild DCM, or at an early stage of the disease echocardiography can show a mild diffuse hypokinesis of the left ventricle (LV) without LV dilatation and with an ejection fraction (EF) being at the lower normal limits or mildly abnormal.
Ventricular size and function can also be assessed very accurately with magnetic resonance imaging (MRI).
Cardiac catheterization and coronary angiography is often necessary to exclude coronary artery disease as the cause of LV dysfunction. Usual hemodynamic findings in cardiac catheterization include an elevated left ventricular end-diastolic pressure and pulmonary capillary wedge pressure and often modest pulmonary hypertension. Left ventriculography demonstrates diffuse contractile dysfunction of a dilated LV.

Treatment of DCM
Standard treatment for heart failure with reduced EF (systolic heart failure) which usually includes an ACE inhibitor, a beta-blocker, a diuretic (usually furosemide) and an aldosterone antagonist (MRA=mineralocorticoid receptor antagonist). Digoxin can be added if there is atrial fibrillation with a relatively rapid ventricular response, or in patients with sinus rhythm but persistent symptoms of heart failure despite the above standard treatment.
Regular exercise (as tolerated) is beneficial. 
Cardiac resynchronization or an  ICD (implantable cardioverter-defibrillator) may be needed in patients with an indication (see the chapter on heart failure for the indications).
For patients with end-stage heart failure, treatment options include ventricular assist devices and heart transplantation.
Video
A case of DCM (left parasternal long-axis view)



Restrictive cardiomyopathy (RCM)
Restrictive cardiomyopathy (RCM) is a rare type of cardiac muscle disease, in which symptoms and signs of congestive heart failure occur in a patient with normal or decreased volume of both ventricles and bi-atrial enlargement (dilatation of both atria). The ventricles have a normal or near-normal systolic function as assessed visually with 2-dimensional imaging or with the ejection fraction, despite the manifestations of heart failure. (More sensitive echocardiographic techniques such as tissue doppler or myocardial strain and strain rate show an impairment of the systolic function, that is not apparent on visual estimation with 2-dimensional imaging or M-mode measurements).  Ventricular wall thickness can be normal or increased (depending on the etiology) and cardiac valves have no significant dysfunction.
 It should be emphasized that the predominant abnormality in these patients is a severely impaired ventricular filling with restrictive physiology, which produces symptoms and signs of heart failure.
The restrictive physiology is caused by severely reduced compliance (elasticity) of the ventricular walls and can be demonstrated by Doppler echocardiography, or cardiac catheterization.
Causes of RCM
The most common cause is amyloidosis.
Other causes: Sarcoidosis, hemochromatosis, Loeffler's endocarditis,  endomyocardial fibrosis, radiation, metastatic cancer, diabetic cardiomyopathy, systemic scleroderma, idiopathic restrictive cardiomyopathy (it can be familial). 
In Loeffler's endocarditis and endomyocardial fibrosis, there is myocardial and endocardial fibrosis apparent in imaging tests (echocardiography or magnetic resonance imaging) and blood tests (complete blood count-CBC) show eosinophilia.
Investigations in RCM
 A chest X-ray may show pulmonary venous congestion. The cardiac silhouette can be normal or mildly enlarged (because of atrial enlargement).
The ECG may show low QRS voltage and nonspecific ST-segment and T-wave abnormalities.
 Echocardiogram demonstrates a normal or near-normal ejection fraction (EF), dilatation of both atria and impaired ventricular filling.
The severely impaired ventricular filling (restrictive physiology) is characterized by the following findings :
Significant dilatation of the atria
Mitral inflow pattern (obtained with the pulse wave doppler at the tips of the mitral valve) with
E wave peak velocity/ A wave peak velocity >1.5
(E wave is the early diastolic velocity of the blood moving through the mitral valve and A wave is an end-diastolic velocity at the time of atrial contraction-absent in atrial fibrillation). The deceleration time (DT) of the E wave (the time from peak velocity of blood flow to zero velocity) is reduced: DT ≤ 150 msec.
( Isovolumic relaxation time is also reduced: IVRT < 60 msec).
Pulse wave Doppler examination of blood flow in a pulmonary vein (performed in the apical 4 chamber view) will show a marked predominance of the D wave (of early diastolic flow through the pulmonary veins) over the S wave (of systolic flow) with
peak S velocity/peak D velocity <0.5  The S and D waves are both positive waves (over the baseline) because they represent flow with direction into the left atrium and towards the transducer (which is at the apex of the heart). The peak velocity of the AR wave (a negative wave of reverse flow from the atrium into the pulmonary vein at end-diastole during atrial systole, in sinus rhythm) is elevated 
(> 35 cm/s). 
Tissue Doppler measurements of the velocity at the mitral annulus demonstrate reduced early diastolic peak velocity (E'): E'< 8 cm/s and E/E' > 15 (this indicates an elevated LV end-diastolic pressure). In this ratio E=the peak velocity of early diastolic blood flow through the mitral valve and E'=the peak early diastolic velocity of the mitral annulus. The first is measured with pulse wave flow doppler through the tips of the mitral valve (in the apical 4 chamber view) and the latter with the pulse wave tissue doppler at the mitral annulus.
In contrast, in constrictive pericarditis peak velocity E' of the septal mitral annulus  > 8 cm/s. The differential diagnosis between restrictive cardiomyopathy and constrictive pericarditis is a classic problem because both conditions produce a clinical picture of heart failure caused by severe diastolic dysfunction.  Another difference between these two entities is the following. In constrictive pericarditis, there is a marked respiratory variation (by more than 30%) of the peak E (early diastolic) blood flow velocity both in mitral and tricuspid flow, with mitral E velocity decreasing in inspiration and tricuspid E velocity increasing in inspiration. This is due to the phenomenon of the ventricular interdependence (for an explanation of this term see the chapter on constrictive pericarditis). This phenomenon of ventricular interdependence does not exist in restrictive cardiomyopathy (RCM), therefore in RCM the respiratory variation in the transmitral and transtricuspid flow is not augmented. In fact, in RCM respiratory variation in flow velocities through the atrioventricular valves is diminished or absent. 
Cardiac catheterization in RCM shows an elevation of filling pressures (diastolic pressures) in both ventricles, and a dip-and-plateau ventricular diastolic pressure tracing (a pattern like the symbol of a square root) is often seen. These are also features of constrictive pericarditis (CP). A difference is that in CP there is an equalization of diastolic pressures of both ventricles (the difference of end-diastolic pressure between the two ventricles is <5 mmHg in CP). On the contrary, in RCM this difference is usually > 5mmHg.  Therefore, careful evaluation of simultaneously recorded LV and RV pressures helps in distinguishing between the two.

 A very useful parameter is the change in these simultaneously recorded ventricular pressures during respiration.
This pressure recording in CP demonstrates discordant changes in systolic pressures with respiration 
(inspiratory increase in RV systolic pressure with a simultaneous decrease in LV systolic pressure/ the opposite in expiration). In contrast, in RCM the change in the systolic pressure of the RV and the LV with respiration is concordant ( they increase or diminish concomitantly and their respiratory changes are small). 
Treatment of RCM
Diuretics are administered for heart failure symptoms, but cautiously (elevations in dosage must be cautious and gradual in order to relieve congestive symptoms, without reducing left ventricular filling pressures to the point of causing hypotension). Beta-blockers are commonly administered, especially if the heart rate is rapid but any reduction in heart rate should be moderate. These patients do not need a slow heart rate because diastolic filling occurs only at the beginning of diastole, so there is no point in increasing the duration of diastole. A slow heart rate in patients with RCM will usually decrease cardiac output and this results in worsening of symptoms. In patients with secondary restrictive cardiomyopathies, specific treatment of the underlying systemic disease is often indicated. In many cases, referral for transplant assessment should be considered early because severe pulmonary hypertension may develop.


Video : A case of RCM due to cardiac amyloidosis 


Cardiac sarcoidosis 


Sarcoidosis is a rare systemic (multisystem) inflammatory disease (age-adjusted incidence of 11 cases per 100,000 population in whites but 34 cases per 100,000 in African Americans. Sarcoidosis most commonly involves the lungs and intrathoracic lymph nodes but it may also involve other organs such as the skin, the liver, the eyes, and the heart (the heart is affected in about 5% of the cases). Its pathologic hallmark is the formation of noncaseating granulomas ( clusters of inflammatory cells without central necrosis).
Cardiac manifestations may include bundle branch block, atrioventricular block (which may manifest with syncope), ventricular arrhythmias/ and or sudden death, atrial arrhythmias, manifestations of heart failure due to diastolic or systolic dysfunction. Echocardiography may show akinesis and thinning, or aneurysm of the basal interventricular septum and/or the basal lateral, inferolateral (posterior) or inferior wall. Other common echocardiographic findings of cardiac sarcoidosis include left ventricular diastolic dysfunction (grade II or III), increased thickness of the right ventricular free wall ( > 5mm at end-diastole in the subcostal view), or increased thickness of the left ventricular wall, systolic dysfunction of either the left ventricle or the right ventricle with non-coronary distribution wall motion abnormalities and aneurysms, mitral regurgitation, or tricuspid regurgitation. Cardiac magnetic resonance imaging with late gadolinium enhancement provides important clues for the diagnosis.
The blood tests in sarcoidosis may show elevated levels of angiotensin converting enzyme, elevated calcium levels, and/ or elevated alkaline phosphatase ( ALP). The chest -X-ray often shows bilateral hilar adenopathy (enlarged hilar lymph nodes) and it may also show indications of interstitial pulmonary disease with a reticulonodular pattern.
The mainstay of medical therapy for cardiac sarcoidosis, as with other organ involvement, is immunosuppression, mostly in the form of corticosteroids. A number of different immunosuppressive agents may be used to avoid the side effects of chronic corticosteroid use.

Arrhythmogenic right ventricular cardiomyopathy (AVRC)

It is also known as arrhythmogenic right ventricular dysplasia. In this condition, inherited as an autosomal dominant trait, patches of the right ventricular myocardium are replaced with fibrous and fatty tissue. Fibrofatty replacement can also occur in the left ventricle. It has a prevalence of approximately 1 per 10000 to 1 per 5000 in the general adult population. The dominant clinical problems are ventricular arrhythmias (ventricular tachycardia-VT, monomorphic with an LBBB pattern, or polymorphic VT), syncope, sudden death, and right-sided heart failure. Common presenting symptoms are palpitations and syncope. Sudden cardiac death due to fatal ventricular arrhythmias is also a common first manifestation (in over 20% of ARVC patients). Right ventricular or biventricular failure occurs in advanced stages of the disease, whereas sudden cardiac death can also occur at an early stage.
The ECG typically shows a slightly broadened QRS complex often with incomplete or complete RBBB  and inverted T waves in the right precordial leads (V1-V3, which are the leads related to the right ventricle). Aepsilon wave can be present i.e. a terminal notch of the QRS (a small wave at the end of the QRS), as a result of slowed intraventricular conduction in an area of the right ventricle.  Often in arrhythmogenic cardiomyopathy, there is low QRS voltage and also right QRS axis deviation is present in many cases, although these findings are less common than T wave inversion. In some cases, the ECG can be normal.  Holter monitoring may demonstrate frequent extrasystoles of right ventricular origin or runs of non-sustained ventricular tachycardia.
 Echocardiography is frequently normal at an early stage, but in more advanced cases it often demonstrates right ventricular dilatation and/or aneurysm of a segment of the RV wall. There may be left ventricular dilatation and dysfunction.
Treatment of ARVC 
Beta-blockers are first-line treatment for patients with non-life-threatening arrhythmias. Amiodarone or sotalol can be used for symptomatic arrhythmias. In cases of life-threatening arrhythmias, or indications of high risk for sudden cardiac death an implanted cardioverter defibrillator (ICD) is required. Obviously, there is an indication for an ICD in patients who had a previous episode of cardiac arrest (aborted SCD) or of hemodynamically unstable sustained ventricular tachycardia (VT), but ICD implantation should also be seriously considered in patients with an episode of hemodynamically stable VT.
 Cardiac transplantation is indicated in some severe cases for end-stage heart failure or for intractable arrhythmia. 
Clinical risk factors that predict an increased risk of sudden cardiac death (SCD) in patients with arrhythmogenic right ventricular cardiomyopathy are the following:
Hemodynamically stable sustained VT

Non-sustained VT
History of unexplained syncope
Severe dilatation and/or dysfunction of the right or the left ventricle, or both
Early-onset  (age < 35 years) of severe structural disease (with prominent ventricular dilatation or dysfunction)
Left heart failure 
Family of history of SCD
An ICD is recommended for patients with ARVC for primary
prevention of SCD if such risk factors are present, as well as for secondary prevention of SCD (i.e. in patients who have been resuscitated and have survived an episode of cardiac arrest or sustained VT) regardless of risk factors.



VIDEO Arrhythmogenic right ventricular cardiomyopathy (or dysplasia)-ARVC or ARVD. A cardiology case is presented in this Video. The findings with ECG and echocardiography and the diagnostic criteria of ARVC (Taskforce-2010) are shown and analyzed. Also, a concise review of the evaluation of the right ventricle (RV function) with echocardiography is presented. ( To watch the video full screen, start the video and click on the symbol [] at the lower right corner).





Another patient ( a male- age 41) with a different myocardial disorder... Describe each view (what kind of view it is what are the interesting findings and which diagnosis could be considered) 
The following images are courtesy of Dr. Vladyslav Kavalerchyk (used with permission).



Image 1
Image 2




Image 3
Image 4
Image 1 is an echocardiographic 2-dimensional apical 4-chamber view. Images 2 and 3 are 3 -dimensional (3D) echocardiographic views (apical 4-chamber) and Image 4 is a frame derived from the cardiac magnetic resonance imaging (MRI) examination of the same patient. All these views show large trabeculations and deep recesses in the apical and lateral segments of the left ventricle, a pattern that strongly suggests left ventricular non-compaction cardiomyopathy with a sponge-like appearance of an area of the left ventricle. Note: There is also a small proportion of the general population with an echocardiographic pattern of prominent left ventricular trabeculations and recesses but without any other abnormalities in left ventricular systolic and diastolic function and in the ECG. Therefore, the presence of recesses and trabeculations is not the only criterion that should be taken into account to make the diagnosis of this cardiomyopathy. Apart from the two characteristic myocardial layers in cardiac imaging, a thick noncompacted internal layer and a thinner compacted external layer, the patient should also have one or more of the following findings in order to be diagnosed with the cardiomyopathy: Symptoms (e.g. palpitations, syncope, exertional dyspnea), a positive family history for cardiomyopathy or sudden death, abnormalities of the ECG (eg. inverted T waves or LBBB), documented arrhythmias (in Holter monitoring or in an exercise ECG test), a reduced left ventricular ejection fraction (EF <50%), or left ventricular wall motion abnormalities, or left ventricular dilation or left ventricular diastolic dysfunction.   For a description of this cardiomyopathy, also see the paragraph below. (The case is courtesy of Dr. Vladyslav Kavalerchyk (used with permission). Also, see the Video : link Left Ventricular Non-Compaction Cardiomyopathy (LVNC)  from Dr. Kavalerchyk's YouTube channel Echocardiography step by step)



Left ventricular non-compaction
Left ventricular non-compaction is a sponge-like appearance of an area of the left ventricle (LV). It results from an arrest of
myocardial maturation during embryogenesis. Familial and spontaneous cases have been described. In patients with LV noncompaction mutations in several genes encoding proteins of the
cytoskeleton, sarcomere, and mitochondria have been implicated.  
The condition predominantly affects the apical segments of the LV and also the mid-inferior and mid-lateral wall. LV non-compaction can be isolated, or it may be associated with congenital heart abnormalities (such as an atrial or ventricular septum defect, or coarctation of the aorta).  
The condition is diagnosed by echocardiography, cardiac MRI (magnetic resonance imaging) or left ventriculography (injection of contrast medium into the LV during cardiac catheterization). On these imaging studies, affected areas have a thick myocardium consisting of a thin compacted outer layer and a thicker noncompacted inner layer. The noncompacted myocardial layer has prominent trabeculations and deep endomyocardial recesses, that communicate with the left ventricular cavity.
 Useful diagnostic criteria are the following:
 The thickness of the noncompacted endocardial layer is > 2 times the thickness of the compacted epicardial layer at end-systole.
The presence of blood flow should be demonstrated (with color flow doppler or contrast echocardiography) in the recesses between the myocardial trabeculations.
The presence of > 3 trabeculations visible in a single image, protruding from the left ventricular wall, apically to the papillary muscles, with intertrabecular spaces connected with the ventricular cavity.
Evidence of systolic and/or diastolic LV dysfunction should be present.
Cardiovascular magnetic resonance imaging (CMR)  permits even better visualization of trabeculations and recesses of the LV myocardium, therefore it is a useful diagnostic test for LV noncompaction.
Important note: There is also a small proportion of the general population with an echocardiographic pattern of prominent left ventricular trabeculations and recesses but without any other abnormalities in left ventricular systolic and diastolic function and in the ECG. Therefore, the presence of recesses and trabeculations and the ratio of the thickness of the noncompacted and the compacted myocardial layer is not the only criterion that should be taken into account to make the diagnosis of this cardiomyopathy. Apart from the two characteristic myocardial layers identified in cardiac imaging, a thick noncompacted endocardial layer and a thinner compacted epicardial layer, the patient should also have one or more of the following findings in order to be diagnosed with the cardiomyopathy: Symptoms (e.g. palpitations, syncope, exertional dyspnea), a positive family history for cardiomyopathy or sudden death, abnormalities of the ECG (eg. inverted T waves, or a left bundle branch block-LBBB, which is a usual finding in these patients), documented arrhythmias (in Holter monitoring or in an exercise ECG test), a reduced left ventricular ejection fraction (EF <50%), or left ventricular wall motion abnormalities of the noncompacted segments, or left ventricular dilation, or left ventricular diastolic dysfunction.
The cardiomyopathy, when present, often leads to the development of heart failure due to systolic and/or diastolic dysfunction. LV non-compaction, especially if it involves an extensive area of the myocardium, can result in congestive cardiac failure, thromboembolism, cardiac arrhythmias, and sudden death. Manifestations can appear in adult age, or in childhood.
Treatment, when necessary, is for associated heart failure (the standard treatment for HF with reduced EF, see chapter on heart failure),  arrhythmias (beta-blockers, amiodarone, or an ICD may be needed depending on the clinical scenario and according to their standard indications), and the risk of emboli (anticoagulation may be needed). Regarding anticoagulation, one must take into account that patients with LV noncompaction with or without atrial fibrillation are at high risk for thromboembolism if they have impaired left ventricular systolic function.
Therefore, anticoagulation with a vitamin K antagonist (warfarin, or acenocoumarol) is recommended in patients with LV noncompaction, with left ventricular EF <40 %, even if they do not have a history of atrial fibrillation.
I also recommend this Video, link: LV hyper-trabeculation or non-compaction in athletes? S.Caselli from the IOC Course on Cardiovascular(CV) Evaluation of Olympic athletes (Youtube channel of Dr. Antonio Pelliccia).

Takotsubo cardiomyopathy
Takotsubo cardiomyopathy is a syndrome of transient apical left ventricular dysfunction (which is apparent with echocardiography or left ventriculography) with a clinical picture that mimics a myocardial infarction (chest pain, or dyspnea, ST-segment elevation, and raised cardiac biomarkers).
Important features of the syndrome are its association with a period of emotional stress, normal epicardial coronary arteries (demonstrated with coronary angiography), and characteristic akinesia of the apical and occasionally also the midsegments of the LV on echocardiography or ventriculography with a good contractile function of the basal segments.
Possible mechanisms include a hyperadrenergic syndrome (i.e. the effects of increased levels of catecholamines), or coronary artery spasm.
Complete recovery of myocardial systolic function usually occurs within 4–6 weeks, but recurrences can occur.

Peripartum cardiomyopathy
This is a rare condition that occurs in the last trimester of pregnancy or within 5 months from delivery (more common between the 36th week of pregnancy and the first month after delivery) and presents clinically and echocardiographically as a dilated cardiomyopathy with left ventricular (LV) systolic dysfunction (with reduced LV ejection fraction) in a patient without a recognizable previous heart disease. This diagnosis is made, when no other cause of LV dysfunction is found.  It is more common in multiparous, obese women over 30 years old. Peripartum cardiomyopathy occurs in about 1 every 2000 live births (this is an approximate number).
Recovery to normal ventricular systolic function within 6 months occurs in nearly half of the cases, but in some patients, peripartum cardiomyopathy can demonstrate a severe course with progressive heart failure, or it can cause sudden death. Thus, it can be a life-threatening condition.

Treatment of peripartum cardiomyopathy before delivery usually includes loop diuretics, beta-blockers, and digoxin. Hydralazine and nitrates can also be added to the above medications. These five drugs are safe in pregnancy and they are considered as the mainstay of heart failure treatment during pregnancy. Pregnant women should not receive angiotensin-converting enzyme inhibitors (ACE-inhibitors), angiotensin receptor blockers, or mineralocorticoid receptor antagonists (MRAs) because of potential teratogenic effects. Postpartum, the treatment is identical to the treatment of any dilated cardiomyopathy (ie. the treatment of heart failure with reduced ejection fraction). Therefore, an ACE-inhibitor (or an angiotensin receptor blocker) usually plus an MRA are also included in the treatment which should comply with the general heart failure guidelines.
 In patients who present with acute peripartum cardiomyopathy, studies have reported a beneficial effect of bromocriptine (a drug that inhibits the secretion of prolactin). Bromocriptine is currently being evaluated in larger studies to assess its cardiovascular effects.
In peripartum cardiomyopathy, heart failure therapy should be continued for a minimum of 12 months after the time of diagnosis or even permanently in cases with severe persistent LV dysfunction.
In some patients who develop severe heart failure not responding to optimal medical treatment the implantation of a left ventricular assist device or heart trasplantation will be required.
There is a risk of relapse of the cardiomyopathy in a susequent pregnancy, therefore the physician should inform the patient regarding this issue. Relapse in a subsequent pregnancy is possible even in women who have fully recovered left ventricular function.
Recommendations of experts about a subsequent pregnancy are the following: In cases with a full recovery of LV function subsequent pregnancy is not contraindicated, but the patient should be informed that although the risk is relatively low, it is not absent. In cases with a partial recovery of LV function, a dobutamine stress echocardiography should be performed before counselling the patient on this issue. If the left ventricular inotropic response to dobutamine is normal, then patients can be counseled as above. If the left ventricular inotropic response to dobutamine is abnormal (ie. there is a reduced LV contractile reserve) then there is a higher risk and pregnancy is not recommended.
In patients with no recovery of LV function, the risk in case of a subsequent pregnancy is high, therefore it must be avoided.

Ramaraj R, Sorrell VL. Peripartum cardiomyopathy: Causes, diagnosis, and treatment. Cleveland Clinic Journal of Medicine 2009 ;76(5):289–96. LINK Peripartum cardiomyopathy: Causes, diagnosis, and treatment.

Hilfiker-Kleiner D, Haghikia A, et al. Peripartum cardiomyopathy: current management and future perspectives. European Heart Journal 2015, doi:10.1093/eurheartj/ehv009
LINK http://eurheartj.oxfordjournals.org/content/early/2015/01/29/eurheartj.ehv009.ful


Tachycardia induced cardiomyopathy
This is a rare form of dilated cardiomyopathy caused by prolonged periods of supraventricular or ventricular tachycardia, which is persistent or very frequent, in order to cause LV systolic dysfunction. Apart from tachyarrhythmias, also very frequent ventricular premature beats (PVCs) with a burden > 10-15% of total QRS complexes in Holter monitoring can occasionally cause this type of cardiomyopathy.

Apart from tachycardia duration, another significant factor that contributes to the development of ventricular dysfunction is the ventricular rate. Patients with higher ventricular rates develop cardiomyopathy earlier.
A clinical problem is determining if the tachycardia is the cause of the cardiomyopathy or if the arrhythmia is a consequence of a cardiomyopathy of different etiology.  Tachycardia induced cardiomyopathy should be suspected in every patient with LV dysfunction in the setting of a persistent tachyarrhythmia when another cause for the LV dysfunction cannot be found.
Tachycardia induced cardiomyopathy is generally reversible once the underlying arrhythmia is controlled, therefore it is important to treat promptly the tachycardia responsible for the condition.
Successful treatment of the causative prolonged arrhythmia usually results in the recovery of cardiac function. Usually, the greatest recovery of the LV ejection fraction (EF) is observed approximately 1 month after arrhythmia cessation and more gradual recovery, which may lead to a complete normalization in many cases, can be observed up to one year thereafter.
 Heart rate normalization, either with rate or rhythm control, is the cornerstone of management. Most of the data available come from patients with atrial fibrillation. In these patients, normalization of heart rate using any of the two methods (rate or rhythm control) improves systolic function, in case of tachycardia-induced cardiomyopathy. However, in other clinical settings, treatment of tachycardia-induced cardiomyopathy should aim at the termination of the responsible arrhythmia, which may require antiarrhythmic drug therapy, direct current (DC) cardioversion, or catheter ablation. For patients with supraventricular tachyarrhythmias, if control of the arrhythmia cannot be achieved by other means, atrioventricular junction conduction ablation combined with pacemaker implantation can be an option.  Drug treatment of heart failure (HF) is also provided, as needed, according to the general indications and guidelines (e.g. an ACE-inhibitor, beta blocker-also useful for the control of heart rate, a loop diuretic, digoxin, aldosterone antagonist, may be needed as part of the HF treatment). 

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Links and Bibliography
 
A VIDEO : I highly recommend this video with clinical questions and most importantly echocardiographic images of various cardiomyopathies ( YouTube -Mayo Clinic -Dr. Steve R. Ommen)
LINK https://www.youtube.com/watch?v=aIlGrMUURQI


Classification of the cardiomyopathies: a position statement from the European society of cardiology 

Maron BJ, Towbin JA, et al Contemporary Definitions and Classification of the Cardiomyopathies. Circulation. 2006;113:1807-1816 (AHA SCIENTIFIC STATEMENT)
LINK http://circ.ahajournals.org/content/113/14/1807


Nishimura RA, Holmes DR. Hypertrophic obstructive cardiomyopathy. N Engl J Med. 2004;350:1320-1327.

Watkins H, Ashrafian H, Redwood C. Inherited cardiomyopathies. N Engl J Med 2011;
364:1643–1656.

Marcus FI, McKenna WJ, Sherrill D, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Circulation. 2010;121:1533-1541

Kushwaha SS, Fallon JT, Fuster V. Restrictive cardiomyopathy. N Engl J Med. 1997;336:267-276.

Behere SP, Weindling SN. Inherited arrhythmias: The cardiac channelopathies.Annals of Pediatric Cardiology. 2015;8: 210-220. LINK https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608198/


Hilfiker-Kleiner D, Haghikia A, et al. Peripartum cardiomyopathy: current management and future perspectives. European Heart Journal 2015, doi:10.1093/eurheartj/ehv009
LINK http://eurheartj.oxfordjournals.org/content/early/2015/01/29/eurheartj.ehv009.ful

Ramaraj R, Sorrell VL. Peripartum cardiomyopathy: Causes, diagnosis, and treatment. Cleveland Clinic Journal of Medicine 2009 ;76(5):289–96. LINK Peripartum cardiomyopathy: Causes, diagnosis, and treatment.

Perez-Silva A, Merino JS, Tachycardia-induced cardiomyopathy E-Journal-of-Cardiology-Practice 2019;7  

Gilotra N, Okada D, Sharma A, Chrispin J. Management of Cardiac Sarcoidosis in 2020. 
Arrhythm Electrophysiol Rev [Internet] 2020 ;9(4):182–8. Available from: 10.15420/aer.2020.09