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 remodelling after a 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 cadiomyopathies includes primary cardiomyopathies characterized by disease involving predominantly the myocardium and secondary cardiomyopathies, i.e. myocardial disease associated with a known specific etiology.
Primary cardiomyopahies include: 
Cardiomyopathies of genetic etiology
Hypertrophic cardiomyopathy, arrhytmogenic right ventricular cardiomyopathy, myocardial non compaction, 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

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
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 characterised by left ventricular hypertrophy with malalignment of the myocardial fibres (myofibril disarray) and myocardial fibrosis. The hypertrophy may be generalised 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 midsystole (because of the LVOT obstruction in midsystole) followed by a second rise
> There is a midsystolic crescendo-decresendo 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 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 obstruction at rest, whereas others only during exercise.  Obstruction is present when the peak intraventricular systolic gradient is ≥ 30 mmHg. Severe obstuction 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 alernatively non dihydropyridine 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 debate regarding which procedure is best. Two basic concerns with percutaneous septal ablation are the following: There is a potential for 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 for 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 absense 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 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 the 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 defirilator) may be needed in patients with an indication (see chapter on heart failure for the indications).
For patients with end stage heart failure treatment options include ventricular assist devices and heart transplantation.
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 of 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
 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 the 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 tranducer (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 demonstrates 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 constritive 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 chapter on constrictive pericarditis). This phenomenon of ventricular interdependence does not exist in restrictive cardiomyopathy (RCM), therefore in RCM the respiratory variation in the trasmitral 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 elevation of filling pressures (diastolic pressures) in both ventricles, and a dip-and-plateau ventricular diastolic pressure tracing (a pattern like the symbol of square root) is often seen. These are also features of contrictive pericarditis (CP). A difference is that in CP there is 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 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 adminisered 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 

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. 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.

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 non compaction 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 resonanse 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 thikness 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 presense 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 an even better visualization of trabeculations and recesses of the LV myocardium, therefore it is a useful diagnostic test for LV non compaction.
The disease usually 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 (anticogulation may be needed). Regarding anticoagulation, one must take into account that patients with LV non compaction 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 non compaction,with
 left ventricular EF <40 %, even if they do not have a history of atrial fibrillation.

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 assossiation with a period of emotional stress, normal epicardial coronary arteries (demonstrated with coronary angiography), and characteristic akinesia of the apical and occasionally also the mid- segments of the LV on echocardiography or ventriculography with 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 of delivery and presents clinically and echocardiographically as a dilated cardiomyopathy with left ventricular systolic dysfunction. 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.
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.

Treatment of peripartum cardiomyopathy, as is the case for every cardiomyopathy of the dilated type, must be in accordance with heart failure guidelines, which include a medical regimen of: angiotensin-converting enzyme inhibitors (or angiotensin receptor-blockers), beta-blockers, diuretics and mineralocorticoid receptor antagonists (MRAs). 
 In patients who present with acute peripartum cardiomyopathy, studies have reported a beneficial effect of bromocriptine (a prolactin-blocker). Bromocriptine is currently being evaluated in larger studies to assess its cardiovasular effects.
In peripartum cardiomyopathy, standard heart failure therapy should be continued for a minimum of 12 months after the time of diagnosis. If cardiac function recovers, cardiac dysfunction can re-emerge if patients are to get pregnant again, therefore, they should be advised on contraceptive measures (Patients should be advised to avoid a future pregnancy). 

Tachycardia induced cardiomyopathy
This is a rare form of dilated cardiomyopathy caused by prolonged periods of supraventricular or ventricular tachycardia, which is peristent or very frequent, in order to cause LV systolic dysfunction.

Appart 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 recovery of cardiac function. Usually the greatest recovery of the LV ejection fraction (EF) is observed approximately 1 month after arrhythmia cessation and a more gradual recovery, which may lead to a complete normalisation in many cases, can be observed up to one year thereafter.
 Heart rate normalisation, 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, normalisation 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, loop diuretic, digoxin, aldosterone antagonist, may be needed as part of the HF treatment). 

LINK: Cardiology book- Table of contents

Links and Bibliography
 A VIDEO : I highly recommend this video with clinical questions and most importantly echocardiographic images of various cardiomyopathies ( You Tube -Mayo Clinic -Dr  Steve R. Ommen)

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)

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;

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

Hilfiker-Kleiner D, Haghikia A, et al . Peripartum cardiomyopathy: current management and future perspectives. European Heart Journal 2015, doi:10.1093/eurheartj/ehv009

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

Tricuspid regurgitation

Tricuspid regurgitation (TR)
Trivial (small) TR is frequently detected by echocardiography in normal subjects, and should never be interpreted as an abnormal finding. 
Pathological TR is more often secondary (not due to a disorder of the valve structure) and less often it is attributed to a primary (structural) valve lesion. 
Secondary TR is due to annular dilatation and increased tricuspid leaflet tethering and is caused by:
1) Right ventricular (RV) pressure overload (usually caused by pulmonary hypertension as a consequence of left sided heart disease, chronic pulmonary disease, connective tissue disease, congenital heart disease, or idiopathic pulmonary hypertension) 
2) RV volume overload (dilatation of the right ventricle due to an atrial septal defect, or due to intrinsic right ventricular disease with systolic dysfunction, as in right ventricular cardiomyopathy).

Primary TR (caused by structural alterations of the valve) can be caused by
 Infective endocarditis (especially in intravenous drug addicts),
Myxomatous disease (leading to prolapse of the valve leaflets)
Rheumatic heart disease,
Iatrogenic causes (
occasionally TR occurs after pacemaker implantation or after endomyocardial biopsy)
Carcinoid syndrome
( carcinoid syndrome, is  a type of neuroendocrine tumor, usually in the small bowel or appendix, with metastases to the liver, which releases serotonin metabolites into the bloodstream. These metabolites are responsible for the formation of endocardial plaques in the right heart chambers. Involvement of the tricuspid valve causes thickening and immobilization of the leaflets, resulting in significant tricuspid regurgitation and, less often tricuspid stenosis.)
Ebstein’s anomaly is a congenital malformation characterized by apical displacement of the annular insertion of the septal and posterior leaflets of the tricuspid valve and atrialization of a portion of the ventricular myocardium.
Endomyocardial fibrosis,
Ergot-like drugs,
Thoracic trauma
Often, even severe TR can be tolerated for a long period of time without significant symptoms. Symptoms of the causative disorder may be present. Eventually, severe TR will produce symptoms of right heart failure, such as fatigue, exercise intolerance, edema, vague abdominal discomfort due to hepatomegaly.
Physical examination in TR
The most common physical signs of severe TR are prominent v waves in the jugular veins and a pulsatile liver. Both these signs are due to regurgitation of right ventricular blood into the systemic veins. 
The systolic murmur of TR is heard at the lower left sternal border and at the xiphoid area. The holosystolic murmur of tricuspid regurgitation (TR) is often soft (and may be absent in many cases of severe TR, if flow is not turbulent enough) and it becomes louder on inspiration.
In severe cases peripheral (ankle or leg) edema, or even ascites may be present.
Frequent findings are an incomplete right bundle branch block and atrial fibrillation.
Echocardiography in tricuspid regurgitation (TR)
TR is identified using color flow mapping of the systolic
regurgitant jet in the right atrium.
Evaluation of the pulmonary systolic pressure from the measurement of the peak velocity of the TR jet should be carried out in all cases. This may be inaccurate in the presence of severe TR (with a large regurgitant volume) because this leads to a lower pressure difference (pressure gradient) between the right ventricle and the right atrium .
The presence of associated lesions, particularly left ventricular systolic or diastolic dysfunction and lesions of the left-sided cardiac valves, should be assessed.
In primary TR, valve morphology can help determine the etiology: vegetations in endocarditis, leaflet retraction and thickened leaflet tips in rheumatic valve disease, prolapsing thickened leaflets in myxomatous disease, a flail leaflet in myxomatous or post-traumatic valve involvement.
In secondary TR annular dilatation or leaflet tethering is observed:
Significant tricuspid annular dilatation is defined in the apical 4 chamber echocardiographic view by a diastolic diameter ≥40 mm , or >21 mm/ mof body surface area. 
Significant tethering of the valve, in secondary TR, is characterized by a coaptation distance > 8 mm. This is the distance between the tricuspid annular plane and the point of coaptation of the valve leaflets in mid-systole from the apical 4-chamber view.
Evaluation of the right ventricular (RV) dimensions and function should be performed.  Indications of RV systolic dysfunction are: Tricuspid annular plane systolic excursion (TAPSE) <15 mm,
 pulse wave TDI-derived peak systolic velocity of the lateral tricuspid annulus <11 cm/s, and
 RV end-systolic area >20 cm2
Tricuspid regurgitation (TR) severity is estimated from the extent of the jet, or better by vena contracta width (vena contracta is the narrowest portion of the jet, near its origin from the valve leaflets). In many cases, just a visual estimate can allow judgment on the severity of regurgitation.  In case of TR with an eccentric jet, a large eccentric jet reaching the posterior wall of the right atrium indicates significant TR.  Conversely, small jets and a normal size of the right atrium and right ventricle usually indicate mild TR.
Regurgitant jet area correlates roughly with the severity of regurgitation:mild <5 cm2 
moderate 6-10 cm2
severe >10 cm2.  

Other more accurate indications of severe TR are:
Vena contracta ≥ 7 mm

In continuous wave Doppler examination of TR, a dense/triangular TR Doppler signal with early peaking.
PISA radius >9 mm, at color Doppler examination with baseline shift, with a Nyquist limit (aliasing velocity) of 28 cm/s towards the direction of the regurgitation.
Effective regurgitant orifice area (EROA) ≥40 mm².
Regurgitant Volume ≥45 ml/beat.
In severe TR, enlargement of the right atrium, right ventricle, and inferior vena cava is almost always present.

Diuretics improve signs of congestion. Specific therapy of the underlying disease is necessary, when feasible.
Surgery (usually tricuspid annuloplasty with a prosthetic ring) is indicated in :
Symptomatic patients with severe primary TR without severe right ventricular dysfunction. 
In asymptomatic or mildly symptomatic patients with severe isolated primary TR and progressive right ventricular (RV) dilatation or progressive deterioration of RV function (class IIa indication).
In patients with severe (indication class I) or moderate (indication class IIa) primary TR, or moderate secondaryTR with dilated annulus (for limits of annular diameter see above) undergoing left-sided valve surgery.
The surgical operation performed is usually annuloplasty with a prosthetic ring, but in advanced forms of tethering and RV dilatation, or in a severe valve deformity that cannot be corrected, valve replacement should be considered. Valve replacement is performed with large bioprostheses (these are preferred than mechanical valves in the tricuspid position).

Tricuspid regurgitation (color doppler echocardiography). A video-link (by dr Luke Howard) :

LINK: Cardiology book- Table of contents

Mitral stenosis

Mitral stenosis (MS)

The most common underlying cause of MS is prior rheumatic fever
occurring, on average, 20 years before presentation of mitral stenosis. 

Rheumatic valve disease is characterized by fibrous thickening and calcification of the valve leaflets, fusion of  the commissures (the borders where the leaflets meet), shortening and thickening of the chordae tendineae.
 Other more rare etiologies of MS include calcification of  the mitral annulus that extends onto the leafets, infective endocarditis with large vegetations obstructing the valve orifice, and rare congenital mitral stenosis (parachute mitral valve, supravalvular mitral ring). In parachute mitral valve, there is a single papillary muscle to which chordae to both leaflets attach. It results in mitral stenosis or mitral regurgitation.
Some systemic diseases can cause valvular fibrosis and stenosis (carcinoid, systemic lupus erythematosus, rheumatoid arthritis, healed endocarditis, mucopolysaccharidosis. 
Mitral valvular fibrosis and stenosis can also be caused by prior anorectic drug use.

Pathophysiology of mitral stenosis (MS)
In the normal heart, the mitral valve opens in early diastole  and blood flows freely rom the left atrium (LA) into the left ventricle (LV). Normally the pressure difference between these two chambers in diastole is negligible (the LA and the LV have almost the same diastolic pressure). The normal cross sectional area of the mitral valve orifice is 4-6 cm2
 In MS, there is obstruction to blood flow across the mitral valve. This produces an abnormal pressure gradient (pressure difference)
between the LA and LV, resulting in an icreased  left atrial (LA) pressure. Hemodynamic changes (a rise in transvalvular pressure gradient) begin when the cross-sectional area of  the valve,  is reduced to less than 2 
In MS the high LA pressure is transmitted retrograde to the pulmonary circulation, resulting in increased pulmonary venous and capillary pressures. The elevated pressure in the pulmonary vasculature may cause transudation of  plasma into the lung interstitium and alveoli. This causes symptoms of heart failure, such as exertional dyspnea and paroxysmal nocturnal dyspnea, or orthopnea. 
In MS, chronic pressure overload of the LA (i.e. the chronically elevated LA pressure) leads to left atrial dilatation. This stretches the atrial conduction fibers and may adversely affect intra-atrial conduction of electric impulses, resulting in atrial fibrillation.
Atrial fibrillation due to the increased heart rate leads to a shortened diastolic period. The contribution of atrial systole to diastolic filling is also lost. These factors worsen the patient's clinical condition, because they result in a further elevation in atrial and pulmonary venous pressures and in a diminished cardiac output. 

Auscultatory findings in MS 
The opening snap is an early diastolic sound of short duration, and it is considered as the most characteristic auscultatory finding of mitral stenosis (MS). You can hear the opening snap near the cardiac apex, but it is more easily heard along the lower left sternal border. However, as the disease progresses and the valve becomes more calcified and immobile, the opening snap may be lost. Also the first heart sound (S1), which is usually accentuated (loud) in MS, for the same reason can become softer at a later stage of the disease. The murmur of MS is a low-pitched rumbling mid-diastolic murmur. It is best heard with the bell of the stethoscope with the patient in the left lateral decubitus position. Presystolic accentuation of the murmur can be present if the patient is in sinus rhythm. Auscultation after a brief period of exercise usually accentuates the murmur of MS, because exercise increases the transvalvular gradient, due to the increased cardiac output and heart rate.
 The  length of the murmur correlates better with the severity of MS than the loudness. MS is more severe when the murmur is longer and when the time interval from the second heart sound (S2) to the opening snap is short.
The electrocardiogram (ECG) in MS, if the rhythm is sinus, shows left atrial enlargement. Atrial fibrillation may be present (it is common in MS). If  pulmonary hypertension has developed, then there is also ECG evidence of right ventricular hypertrophy.
 Echocardiography in MS 
It shows structural abnormalities of the valve (in rheumatic MS  mitral leaflets are thickened with abnormal fusion of  their commissures). Echocardiography also shows restricted separation
of the valve leaflets and doming of leaflets during diastole.
 Left atrial enlargement is also present.
The mitral valve area (MVA) can be measured directly from the parasternal short axis view at the level of the tips of the mitral valve. Optimal positioning of the echocardiographic view, in order to obtain this measurement, is done by first obtaining a parasternal long-axis view and placing the mitral valve orifice in the center of the scan plane. The transducer is then rotated 90° to obtain the short-axis view. Measurements are obtained at the tips of the mitral leaflets. Three-dimensional echocardiography can provide a more accurate determination of the mitral valve area (MVA).
MVA can also be calculated from Doppler velocity measurements (the diastolic pressure half time). In general, the pressure half time (PHT) represents the time in which the peak pressure gradient between two adjacent chambers decreases to the half of its value. Thus, the PHT is the time it takes for the pressure gradient across the valve to fall to one-half the starting value. (This is equal to the time for the velocity of the mitral E wave to decrease to 70% of peak velocity). The mitral inflow E wave is used in this calculation.
 MVA (in cm2) = 220/PHT. 
PHT is measured by tracing the deceleration slope of the E wave on a continuous wave Doppler recording of diastolic mitral flow. In some cases, the deceleration slope can be bimodal with a more rapid decline of mitral flow velocity in early diastole. Then  it is recommended to trace the deceleration slope in mid-diastole rather than the early one.

Another method to determine the mitral valve area (MVA) is the PISA (proximal isovelocity surface area) method, a method also used (more commonly) for the calculation of the effective regurgitant oriffice in cases of mitral regurgitation. In mitral stenosis (MS) the PISA method can be used to calculate the MVA and it offers the advantage of being still accurate in case of concomitant mitral or aortic regurgitation. 
On the atrial side of the stenotic mitral valve, diastolic flow converges towards the stenotic valvular orifice, producing multiple hemispheres of isovelocity (the velocity of blood is the same in every point of the surface of each of these converging hemispheres). As blood accelerates towards the stenotic orifice, the velocity at the outer hemispheres is lower than the velocity on the smaller inner hemispheres. If π=3.14, r (in cm) is the PISA radius (the radius of flow convergence) which is the radius of the hemisphere where blood velocity is the aliasing velocity  and a is the opening angle of mitral leaflets, i.e. the angle between the two mitral leaflets at the atrial surface (in degrees), aliasing velocity is the velocity at which aliasing of color doppler occurs in the direction of flow through the mitral valve (this is set by the echocardiographer to 20-45 cm/s), then we can use the equation: 
MVA= 2π r2  x (aliasing velocity/peak MS velocity) x (a/180).
 MVA=6,28 r2  x (aliasing velocity/peak MS velocity) x (a/180)

 Measurement of the opening angle is demanding, however it has
been demonstrated that there is only a slight difference in the angle
between patients and the use of a fixed angle of 100 degrees can provide an accurate estimation of MVA.
Current guidelines define clinically important, severe, MS as a valve area ≤1.5cm2  , because this valve area is typically accompanied by left atrial enlargement and elevated pulmonary artery systolic pressure. A valve area ≤1.0 cm2 is termed "very severe" MS.
The transvalvular mean gradient (assessed by means of tracing mitral inflow continuous wave doppler signal) provides an estimate of stenosis severity. In mild stenosis : mean gradient < 5 mm Hg Moderate stenosis : mean gradient between 5 and 10 mm Hg.
 Severe MS : mean gradient > 10 mm Hg. 
Tricuspid regurgitation (TR)  often accompanies severe MS. It may be secondary to right ventricular dysfunction and tricuspid annular dilation or may be the result of the rheumatic involvement of the tricuspid valve 

Treatment of MS
 Symptoms due to vascular congestion can be improved by restriction of salt intake and diuretic therapy.
Heart rate slowing agents, such as beta-blockers or nondihydropyridine calcium channel blockers (diltiazem or verapamil), increase diastolic left ventricular filling time and so they there decrease symptoms with exercise. These drugs, or digoxin, are also used to slow the ventricular rate in patients with rapid atrial brillation. Anticoagulant therapy to prevent thromboembolism is indicated  in MS patients with atrial fibrillation, or an identied LA thrombus, or a prior embolic event.
Percutaneous or surgical valve interventions are the only treatments that alter the natural history of severe MS. They are indicated in patients with severe (see above for the echocardiographic criteria of MS severity), symptomatic MS. Percutaneous mitral balloon 
 valvuloplasty is the treatment of  choice in appropriately selected patients (those without advanced anatomic deformity of  the valve, and without moderate or severe mitral regurgitation, or left atrial thrombus). Transesophageal echocardiography (TEE) is indicated to exclude LA thrombus prior to valvuloplasty.
Percutaneous mitral valvuloplasty (PMV) is also indicated for asymptomatic patients with severe MS (valve area  ≤1.5cm2) , who have pulmonary hypertension (pulmonary artery systolic pressure > 50 mm Hg at rest or > 60 mm Hg with exercise) if valve morphology is favorable for PMV, in the absence of left atrial thrombus or moderate to severe mitral regurgitation.
In patients with severe MS causing symptoms, not suitable for percutaneous valvuloplasty, surgical treatment is indicated. This is true for patients with severe subvalvular disease or severe valvular calcification, or concomitant mitral regurgitation (moderate or severe). Surgical treatment choices include: 
Open mitral valvotomy: It involves direct visualization of the mitral valve (with cardiopulmonary bypass), debridement of calcium, and splitting of fused commissures and chordae.
 Mitral valve replacement.with a prosthetic valve is often required, when there is extensive fibrosis and calcification or concomitant moderate to severe mitral regurgitation.

LINK: Cardiology book- Table of contents

Mitral stenosis and echocardiography. A good video by 123sonography

An echocardiogram of a patient with mitral stenosis (by dr Maged Al Ali)

Baumgarther H, et al. 2017 ESC/EACTS Guidelines for the management of valvular heart disease: The Task Force for the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS), European Heart Journal, , ehx391,

Bradyarrhythmias-Bradycardia : Diagnosis and treatment and a case-quiz

Note: The site is under develoment and content is continuously expanding
Cardiology free e-book online ECG QUIZ 1. An electrocardiography CASE-QUIZ:  A patient with weakness and lightheadedness. What is the diagnosis and which should be the management ?
Watch the video and answer the question. Click on the symbol [] at the lower right corner of the video to see it enlarged: full screen)


Heart rate (ventricular rate) 30- 35/min. P waves are more frequent than the QRS complexes and they do not have any temporal relation with QRS complexes (some P waves even fall in the ST segment). This is a case of complete atrioventricular block.  QRS has a right bundle branch block morphology. In general, complete atrioventricular (AV) block would be an indication for permanent pacing, but in this case the complete (third degree) AV block could be possibly caused by verapamil, which the patient has been taking for hypertension. So there is a potentially reversible cause for the AV block. When we suspect a reversible cause we do not implant a permanent pacemaker. Instead there is an indication for temporary pacing and discontinuation of the causal drug. The patient was admitted to the hospital, verapamil was discontinued and replaced by another antihypertensive agent, with no effect on conduction. The patient remained under observation with temporary transvenous pacing for 2 days. Two days after the discontinuation of verapamil the normal heart rhythm (normal atrioventricular conduction) recovered. So a permanent pacemaker was not implanted. 
In cases, where the complete AV block persists and is not reversible, or if there is no revesible cause for the block, implantation of a permanent pacemaker is absolutely indicated.

Bradycardia is a ventricular rate (at rest) < 50 beats per minute (bpm)  (cycle length 1200 ms). Some cardiologists use 60 bpm (cycle length 1000 ms) as the lower limit of the  normal resting heart rate. Bradycardia is not always an abnormal finding. It can be normal, especially in the absence of symptoms. Trained athletes, especially endurance athletes, usually have bradycardia at rest and this is normal.
Bradycardia due to an abnormality of the conducting system of the heart is called "bradyarrhythmia". Many of these rhythm disorders are asymptomatic and benign, requiring no treatment, whereas some cause symptoms and need treatment with pacemaker implantation and others can be life threatening requiring rapid intervention.
Symptoms of bradycardia or bradyarrhythmias are nonspecific (i.e. the symptom is not always directly correlated to the bradycardia and other causes should also be sought). Symptoms include: fatigue, generalized weakness,  lightheadedness, presyncope, syncope, dyspnea on exertion. 

Bradyarrhythmias arise from abnormalities in one or more of three locations in the heart's conducting system: sinoatrial node, atrioventricular node, or infranodal (the His -Purkinje system).

A female patient 78 years old with a history of hypertension and one-vessel coronary artery disease treated with a percutaneous coronary intervention (PCI) of the right coronary artery 3 years before (because of effort angina). She also has a history of asthma. One year before she had a myocardial perfusion scintigraphy (a technetium 99m SPECT scan) which did not reveal any ischemia of significant extent or any myocardial scar. She complains of episodes of fainting, or near-fainting (one episode of syncope and two presyncopal episodes during the last month). She is currently on medication with irbesartan -hydrochlorothiazide 300/25 mg per day, aspirin 100 mg per day ,atorvastatin 20 mg per day and an inhaled bronchodilator. Physical examination is normal and it also did not reveal orthostatic hypotension. Her blood tests revealed no significant abnormalities. Her 12 lead  ECG shows sinus rhythm, a prolonged PR interval (first degree AV block) and a LBBB . Here is a part of her 24-hours Holter ECG recording. The patient did not have any symptoms during the recording. What are the findings ?  Which  could be the most probable cause ?  What treatment do you propose ?


The presence of PR prolongation and/or a bundle branch block in a patient with presyncopal or syncopal episodes, should raise a suspicion of a bradyarrhytmic cause (e.g. pauses due to sinus node dysfunction, or a transient second or third degree atrioventicular block). In this case the holter ECG recording shows sinus pauses with a duration of about 3-3,5 seconds. The most probable cause of sinus node dysfunction in this age group is idiopathic degenerative fibrosis of the conductive system. The patient does not take any medications whith an influence on sinus node function. A permanent pacemaker (type DDDR) was implanted and the patient is asymptomatic since then. (There was a class II indication for permanent pacing, since there is ECG evidence of sinus node dysfunction and symptoms compatible with the disorder are present, in the absense of another identifiable cause. If the patient had symptoms at the time of the recorded pauses, then the indication for pacing would be absolute- class I).

Sinus nodal or sinoatrial nodal (SA nodal) dysfunction (sick sinus syndrome) 
Causes of sinus node dysfunction have been classified as intrinsic or extrinsic. This classification is practical because extrinsic causes are often reversible. In this case they should be corrected (if it is possible) and this way unnecessary pacemaker therapy can be avoided. The most common causes of extrinsic sinus node dysfunction are drugs and influences of the autonomic nervous system (stimulation of the parasympathetic nervous system via the vagus nerve or inhibition of the activity of the sympathetic nervous system can suppress automaticity and/or slow conduction).
Drugs that can cause sinus node dysfunction are beta-blockers, non-dihydropyridine calcium channel blockers (verapamil, diltiazem), digoxin, ivabradine, antiarrhythmic drugs, such as type IA (quinidine, procainamide, disopyramide) ,Type IC (flecainide and propafenone) Type III (sotalol and amiodarone), sympatholytic antihypertensives (clonidine, methyldopa, reserpine) and other miscellaneous drugs (lithium, cimetidine, amitriptyline, phenytoin).
Causes of sinus node dysfunction related to effects of the autonomic nervous system include vasovagal syncope and generally situations of excessive vagal tone, the carotid sinus syndrome and endotracheal suctioning (via activation of the vagus nerve).
 Other extrinsic causes include hypothyroidism, sleep apnea, hyperkalemia, increased intracranial pressure, sepsis, hypothermia and hypoxia.
Intrinsic sinus node dysfunction is often degenerative due to fibrous replacement of the sinus node or its connections to the atrium. This is more common in elderly individuals.
Other causes of intrinsic sinus node dysfunction are :
Acute and chronic coronary artery disease (in the setting of acute myocardial infarction, typically inferior, the abnormality can be transient).
 Inflammatory processes such as myocarditis (e.g viral myocarditis), rheumatic heart disease, systemic lupus erythematosus (SLE), rheumatoid arthritis and mixed connective tissue disease. 
Congenital heart disease (transposition of the great arteries/Mustard and Fontan repairs)

Familial causes of sinus node disease (miscellaneous genetic causes and also in rare familial syndromes such as Kearns-Sayre syndrome and myotonic dystophy.
Iatrogenic damage of the sinus node from direct injury in cardiothoracic surgical procedures, or radiotherapy.
Sinus node dysfunction (sick sinus syndrome) can be manifested with: sinus bradycardia (with heart rate ≤ 50/min)
Sinus pauses, of duration > 2 seconds ( Generally pauses < 3 seconds are not a serious concern. However, pauses > 3 seconds while the patient is awake are generally concidered abnormal). For a description of sinus pauses and sinoatrial exit block see below.
Chronotropic incompetence: inability to attain 80% of the maximum predicted heart rate in response to exercise. It can be  associated with symptoms (such as fatigue, reduced exercise toleralce, dizziness with exercise). 
The "tachy-brady" (tachycardia-bradycardia) syndrome: when there are alternating periods of a supraventricular tachycardia (most commonly atrial fibrillation, but atrial flutter, or atrial tachycardia can also occur) with periods of sinus bradycardia or sinus pauses > 2 seconds. In patients with tachycardia-bradycardia syndrome after conversion of tachyarrhythmias, long pauses may occur (post-conversion pause). Sinus bradycardia in some patients can facilitate the occurence of reentrant tachycardias, by magnifying discrepancies in the duration of the refractory period between different areas of the cardiac tissue. This is a phenomenon that occurs with longer cycle lengths.
 Sinus pauses
The sinus node may fail to deliver an electrical impulse to the atria for a time interval and this is manifested on the ECG by the absence of P waves and also absence of cardiac electical activity, until a sinus impulse appears, or until an escape pacemaker (an other focus of conductive tissue) depolarizes and generates an impulse. This can happen because of a sinus arrest or sinus pause, which occurs when the sinus node does not depolarize on time, or because of sinoatrial (SA) exit block. In SA exit block the sinus node generates electrical impulses, some of which are blocked on their exit from the sinus node to the atrial tissue. SA exit block produces on the ECG an abnormality very similar to sinus arrest. SA exit block may be distinguished from sinus arrest by the fact that the pause is a multiple of the sinus PP interval (the interval between two consecutive sinus P waves before the pause)
Brief, asymptomatic sinus pauses are a common finding and do not require treatment. Generally pauses < 3 seconds are not a serious concern and can be seen in Holter ECG monitoring in up to approximately 10% of normal persons. They are also more common in athletes. Pauses lasting > 3 seconds, especially if they occur while the patient is awake are considered abnormal.

For sinus node dysfunction (sick sinus syndrome) implantation of a  permanent pacemaker is generally indicated only when symptoms that correlate to this disorder 
are present -this is a class I indication (or it may be indicated if symptoms compatible with the disorder are present, in the absense of another identifiable cause-a class II indication). These pacing indications are valid for cases where sinus node dysfunction is not the result of a reversible cause. 3) Sinus node disease. 
Pacing is not indicated in patients with sinus node dysfunction, or sinus bradycardia which is asymptomatic or due to reversible causes.
Atrioventricular (AV) node or His-Purkinje system disorders (disorders of atrioventricular conduction)
Their etiologies  can classified as functional (which are often reversible) or structural.  The most common cause of atrioventricular (AV) block is idiopathic fibrosis of the heart's conductive system (Lenegre’s disease and Lev’s disease). This, of course, is a structural cause and it is not reversible also.
Other structural causes include: Acute myocardial infarction (MI) : AV block in patients with acute inferior MI is more common (occuring approximately in 14%-15 % of patients) and less common in those with anterior infarction, (2%). AV block occurs usually within the first 24 hours of an acute MI, most commonly, it is first-or second-degree AV block, but complete heart block can also occur. In acute inferior MI the level of block is usually in the AV node, resulting in more stable, escape rhythms with narrow QRS complex . In contrast in acute anterior MI  the level of block is usually  in the His bundle, or bundle branches resulting in unstable escape rhythm with a wide QRS complex and a worse prognosis (high mortality rates).
Chronic coronary artery disease can also cause AV block.
Calcific valvular disease
Cardiomyopathies and infiltrative diseases of the heart can also cause disorders of AV conduction (AV block). Infiltrative diseases are conditions caused by the accumulation in tissues of substances or cells  not normally found in those tissues, such as amyloidosis, hemochromatosis and sarcoidosis 
Infectious and inflammatory disorders such as endocarditis myocarditis (Chagas disease, Lyme disease, rheumatic fever, etc)
Collagen vascular diseases (scleroderma, rheumatoid arthritis, systemic lupus erythematosus, Reiter’s syndrome, ankylosing spondylitis, and polymyositis)
Iatrogenic AV block is not uncommon. It may occur as a consequence of mitral or aortic valve surgery, or catheter ablation.
Congenital heart disease, such as congenital complete heart block ostium primum atrial septal defect and transposition of the great vessels can also cause AV block
Functional causes of AV block are common and include drugs ( beta-blockers, nondihydropyridine calcium channel blockers digoxin, antiarrhythmic drugs)
Effects exerted via the autonomic nervous system ( vasovagal syncope, carotid sinus syndrome) hyperkalemia, hypermagnesemia.

Atrioventricular (AV) node or His-Purkinje system disorders can be manifested as:
A first-degree AV blockPR interval prolongation  (PR duration >200 ms).
A second-degree AV block, which is further classified in two types:
Mobitz I (Wenckebach): The ECG shows progressive PR interval
prolongation followed by a single blocked P wave. In some cases the progressive lengthening of the PR interval may be subtle. The best way to assess it is to measure the PR interval of the beat which is immediately prior to a blocked P wave and the PR of the beat  immediately after a blocked P wave. The latter should be shorter.
In this type of atrioventricular (AV) block, the most common site of block is in the AV node.
Mobitz II: There is no progressive PR interval prolongation
before a blocked P wave. The PR interval is constant but there is intermittent conduction of the atrial electrical impulses to the ventricles, so that some P waves are not followed by a QRS complex. In Mobitz II AV block, the most common site of block
is infranodal (in the His-Purkinje system).

A special case is a 2:1 AV block, where every second P wave is conducted to the ventricles (followed by a QRS).

Third-degree (complete) AV block, or complete heart block
There is no temporal association between P waves and QRS
complexes, because there is no conduction of atrial impulses (P waves) to the ventricles. Thus, the ventricular rhythm is an escape rhythm originating from a secondary pacing site and not from transmission of sinus impulses.
This ventricular escape rhythm, if it is characterized by narrow QRS complexes, is called a junctional escape rhythm. Usually in these cases the site of block is in the AV node.
If QRS complexes are wide (≥ 120 msec) the block is infranodal, i.e. below the AV node,  in the His- Purkinje system.
The autonomic nervous system exerts an important effect on the function of the AV node but it only minimally influences the His bundle and the distal conducting system. Thus, the influence of the autonomic system on the production and conduction of electrical impulses in the heart is mainly on the sinus node and the AV node.
The AV node is highly innervated with postganglionic sympathetic and parasympathetic nerves.
Treatment of bradycardia and heart block is needed if there are symptoms such as syncope, lightheadedness, dyspnea (shortness of breath), ischemic chest pain and/or evidence of hemodynamic compromise or low cardiac output. If bradycardia is attributed to the effect of a drug, then this drug should be discontinued, if possible.However, if cessation of drug therapy considered as the cause of the bradycardia for a reasonable duration of time does not result in improvement, or drug therapy is needed for an indication (e.g. a paroxysmal tachyarrhythmia) then the implantation of a permanent pacemaker should be considered.
If rapid treatment of bradycardia is needed, because of the presense of serious symptoms, or hypotension the next step is intravenous administration of atropine. Infusion of isoproterenol, may be required in acutely decompensated patients if atropine fails, until pacing can be initiated. Temporary pacing is more effective than atropine or isoproterenol for decompensated patients with serious bradycardia. Temporary pacing includes:
External transcutaneous pacing, which can be rapidly and easily instituded, but it is used only for a short period of time, due to the unpredictable transcutaneous capture and also because it is poorly tolerated by the patient.
Transvenous temporary pacing, via the insertion of a pacing electrode through the subclavian or the internal jugular vein into the right ventricle. This is the most effective and reliable method of temporary pacing.

Implantation of a permanent pacemaker is indicated in all patients with symptomatic bradycardia (caused by sinus node dysfunction, or any type of second or third degree AV block-even Mobitz I if it results in symptoms), when bradycardia is not due to a reversible cause. When symptomatic sinus bradycardia, sinus pauses, or AV block is attributed to the effects of drug treatment (for examle treatment with beta blockers, diltiazem, verapamil, or antiarrhythmic agents) the following general rules should be followed : 
If this treatment is not absolutely necessary, these drugs should be disontinued. Then, if the bradyarrhythmia terminates, no pacemaker is indicated. 
If symptomatic bradycardia is attributed to an absolutely necessary drug treatment, then a permanent pacemaker is implanted and drug treatment is continued.
 A permanent pacemaker is also indicated  in asymptomatic patients with aqcuired Mobitz type 2 block,  or complete (third degree) AV block, because these types of block are assossiated with a high risk for the development of profound bradycardia and syncope (This is a class I indication according to ESC guidelines on cardiac pacing-2013).
 Permanent pacing is also indicated in 2:1 infranodal block, and it  should be considered in patients with second-degree type 1 AV block if it causes symptoms or if it is found to be located at intra- or infra-His levels at an electrophysiologic study.(This is a class IIa indication, according to the ESC guidelines on cardiac pacing-2013). Pacing is not indicated in patients with AV block which is due to reversible causes (i.e. a class III indication).

LINK: Cardiology book- Table of contents

Bibliography and useful links :

AHA Guideline: Management of Symptomatic Bradycardia and of Symptomatic Tachycardia in the acute setting.

ESC (2013) Guidelines on cardiac pacing and cardiac resynchronization therapy

Deal N.Evaluation And Management Of Bradydysrhythmias In The Emergency Department. Emergency Medicine Practice, 2013;15:1-16.

Focused Update Incorporated Into the ACCF/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities

ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities