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MYOCARDIAL AND
ENDOCARDIAL DISEAS
ATRIAL MYXOMA
This is the most common primary cardiac tumour. It occurs at all ages and
shows no sex preference. Although most myxomas are sporadic, some are
familial. Histologically they are benign. The majority of myxomas are
solitary, usually develop in the left atrium and are polypoid, gelatinous
structures attached by a pedicle to the atrial septum. The tumour may
obstruct the mitral valve or may be a site of thrombi that then embolize. It
is also associated with constitutional symptoms: the patient may present
with dyspnoea, syncope or a mild fever. The physical signs are a loud
first heart sound, a tumour 'plop' (a loud third heart sound produced as the
pedunculated tumor comes to an abrupt halt), a mid- diastolic murmur,
and may be signs due to embolization. A raised ESR is usually present.
The diagnosis is easily made by echocardiography because the tumour is
demonstrated as a dense spaceoccupying lesion . Surgical removal
usually results in a complete cure.
Myxomas may also occur in the right atrium or in the ventricles. Other
primary cardiac tumours include rhabdomyomas and sarcomas.
MYOCARDIAL DISEASE
Myocardial disease that is not due to ischaemic, valvular or hypertensive
heart disease or a known infiltrative, metabolic/toxic or neuromuscular
disorder may be
caused by:
■ an acute or chronic inflammatory pathology (myocarditis)
■ idiopathic myocardial disease (cardiomyopathy).
Myocarditis
Acute inflammation of the myocardium has many causes. Establishment
of a definitive aetiology with isolation of viruses or bacteria is difficult in
routine
clinical practice.
In western societies, the commonest causes of infective myocarditis are
Coxsackie or adenoviral infection. Myocarditis in association with HIV
infection is seen at postmortem in up to 20% of cases but causes clinical
problems in < 10% of cases. Chagas' disease, due to Trypanosoma cruzi,
which is endemic in South America, is one of the commonest causes of
myocarditis world-wide.
Additionally toxins (including prescribed drugs), physical agents,
hypersensi tivity reactio ns and aut oimmune conditions may also cause
myocardial inflammation.
Causes of myocarditis
Idiopathic
Infective Viral: Coxsackievirus, adenovirus,CMV, echovirus, influenza,
polio, hepatitis, HIV
Parasitic: Trypanosoma cruzi, Toxoplasmagondii (a cause of myocarditis
in the newborn or immunocompromised)
Bacterial: Streptococcus (most commonly rheumatic carditis), diphtheria
(toxin-mediated heart block common)
Spirochaetal: Lyme disease (heart block common), leptospirosis
Fungal Rickettsial
Toxic
Drugs Causing hypersensitivity reactions, e.g. methyldopa, penicillin,
sulphonamides, antituberculous
Radiation May causemyocarditis but pericarditis more common
Autoimmune An autoimmune form with autoactivated T cells and
organ-specific antibodies may occur
Clinical features
Myocarditis may be an acute or chronic process; its clinical presentations
range from an asymptomatic state associated with limited and focal
inflammation to fatigue, palpitations, chest pain, dyspnoea and fulminant
congestive cardiac failure due to diffuse myocardial involvement. An
episode of viral myocarditis, perhaps unrecognized and forgotten, may be
the initial event that eventually culminates in an 'idiopathic' dilated
cardiomyopathy. Physical examination includes soft heart sounds, a
prominent third sound and often a tachycardia. A pericardial friction rub
may be heard.
Investigations
■Chest X-ray may show some cardiac enlargement, depending on the
stage and virulence of the disease.
■ECGdemonstrates ST andT wave abnormalities and arrhythmias. Heart
block maybe seen with diphtheritic myocarditis, Lyme disease and
Chagas' disease (see
below)
■ Cardiac enzymes are elevated.
■Viral antibody titres may be increased. However, since enteroviral
infection is common in the general population, the diagnosis depends on
the demonstration of acutely rising titres.
■Endomyocardial biopsy may showacute inflammation but false
negatives are common by conventional criteria. Biopsy is of limited value
outside specialized
units.
■Viral RNA can be measured from biopsy material using polymerase
chain reaction (PCR). Specific diagnosis requires demonstration of active
viral
replication within myocardial tissue.
Treatment
The underlying cause must be identified, treated, eliminated or avoided.
Bed rest is recommended in the acute phase of the illness and athletic
activities should be
avoided for 6 months. Heart failure should be treated conventionally with
the use of diuretics, ACE inhibitors, beta-blockers, spironolactone
+digoxin. Antibiotics should be administered immediately where
appropriate. NSAIDs are contraindicated in the acute phase of the illness
but may be used in the late phase. The use of corticosteroids is
controversial and no studies have demonstrated an improvement in left
ventricular ejection fraction or survival following their use. The
administration of high-dose intravenous immunoglobulin on the other
hand appears to be associated with a more rapid resolution of the left
ventricular dysfunction and improved survival. Novel and effective
antiviral,
immunosuppressive
(e.g.
gamma-interferon)
and
intmunomodulating (e.g. IL-10) agents are currently undergoing animal
trials and may become available in the future to treat viral myocarditis.
Giant cell myocarditis
This is a severe form of myocarditis characterized by the presence of
multinucleated giant cells within the myocardium. The cause is unknown
but it maybe associatedwith sarcoidosis, thymomas and autoimmune
disease. It has a rapidly progressive course and a poor prognosis.
Immunosuppression is recommended.
Chagas' disease
Chagas' disease is caused by the protozoan Trypanosoma cruzi and is
endemic in South America where upwards of 20 million people are
infected. Acutely, features of myocarditis are present with fever and
congestive heart failure. Chronically, there is progression to a dilated
cardiomyopathy with a propensity towards heart block and ventricular
arrhythmias. Amiodarone is helpful for the control of ventricular
arrhythmias; heart failure is treated in the usual way.
CARDIOMYOPATHY
Cardiomyopathy is a general term indicating disease of the cardiac
muscle. Diseases are classified on predominant clinical presentations:
■dilated cardiomyopathy - ventricular dilatation
■hypertrophic cardiomyopathy – myocardial hypertrophy
■restrictive cardiomyopathy - impaired ventricular filling
■arrhythmogenic right ventricular cardiomyopathy - prominent right
ventricular involvement with a high frequency of ventricular arrhythmias
■other rare cardiomyopathies.
Dilated cardiomyopathy (DCM)
DCM is characterized by dilatation and impaired systolic function of the
left and/ or right ventricle, in the absence of abnormal loading conditions
(e.g. hypertension, valve disease) and coronary disease. The aetiology in
the majority of cases is unknown and in most patients no cause is found
('idiopathic').
A large number of cardiac and systemic diseases can cause cardiac
dilatation and systolic impairment. Other potential causes of DCM
include persistent viral infection and autoimmune disease. Evidence for
the latter includes associations with specific HLA subtypes and the
frequent finding of circulating cardiac-specific
autoantibodies.
At least 25% of the 'idiopathic' cases are known to be familial . In the
majority of familial cases inheritance is autosomal dominant, but
X-linked and recessive cases occur. In a limited number of cases the
responsible genes have been identified.
The aetiology in the majority of cases remains unknown.
Causes of dilated cardiomyopathy (DCM)
Genetic e.g. autosomal dominant DCM, X-linked cardiomyopathy
Inflammatory Post-infective, autoimmune, connective tissue diseases
(systemic
lupus erythematosus, systemic sclerosis)
Metabolic e.g. glycogen storage diseases
Nutritional Thiamin, selenium deficiency
Endocrine Acromegaly, thyrotoxicosis, myxoedema, diabetes mellitus
Infiltrative Hereditary haemochromatosis
Neuromuscular
e.g.
muscular
dystrophy,
Friedreich's
ataxia,
mitochondrial myopathies
Toxic Alcohol, cocaine, doxorubicin, cyclophosphamide, cobalt
Haematological Sickle cell anaemia, thrombotic thrombocytopenic
purpura
Clinical features
Presentation is generally with congestive heart failure and therefore
symptoms and signs are those of left and/ or right heart failure.
Additionally, patients may present
with syncope due to ventricular arrhythmia or conduction disease or with
pulmonary or systemic embolism.
Occasionally, initial presentation is with sudden cardiac death.
Increasingly, evaluation of relatives of DCM patients is allowing
identification of early asymptomatic disease, prior to the onset of these
complications. Clinical evaluation should include careful family history
and construction of a pedigree where appropriate.
Investigations
■ Chest X-ray demonstrates generalized cardiac enlargement.
■ECG shows diffuse non-specific ST segment and T wave changes.
Sinus tachycardia, conduction abnormalities and arrhythmias (i.e. atrial
fibrillation,
ventricular premature contractions or ventricular tachycardia) are also
seen.
■Echocardiogram reveals dilatation of the left and/or right ventricle
with poor global contraction function.
■Angiography should be performed to exclude coronary artery disease
in all individuals at risk (generally patients > 40 years or younger if
symptoms
or riskfactors are present).
■Biopsy is generally not indicated outside specialist
Treatment
The goals of management are to relieve symptoms, retard disease
progression and prevent complications. Treatment involves conventional
management of heart failure. Diuretics are highly effective for the relief
of congestive symptoms but should not be used in isolation since they
exacerbate activation of neurohormones that may contrib ute to disease
progression. Disease progression is retarded by the use of ACE-inhibitors,
angiotensin II receptor antagonists and spironolactone to
antagonize activation of the renin-angiote nsinaldosterone system
(RAAS), while beta-blockers act similarly on the sympathetic nervous
system. These are indicated in most cases. Beta-blockers may also help
prevent arrhythmias. In specific cases, permanent pacing, anti-arrhythmic
therapy or implantable cardioverter defibrillators may be indicated.
Severe ventricular dilatation and dysfunction, documented atrial
fibrillation or a history of embolization are indications for anticoagulant
treatment. Cardiac transplantation remains the principal option for
advanced disease refractory to medical therapy. Potential alternatives to
transplantation are discussed in the section on heart failure .
There is currently no specific treatment for idiopathic DCM although
preliminary studies have investigated the role of growth hormone,
immunoadsorption and anticytokine therapy.
Hypertrophic cardiomyopathy (HCM)
Hypertrophic cardiomyopathy is characterized by variable myocardial
hypertrophy, most commonly involving the interventricular septum, and
disorganization ('disarray ') of cardiac myocytes and myofibrils.
Twenty-five per cent of patients have dynamic left ventricular outflow
tract obstruction due to
the combined effects of hypertrophy, systolic anterior motion (SAM) of
the anterior mitral valve leaflet and rapid ventricular ejection.
The majority of cases are familial, autosomal dominant, and due to
mutations in the genes encoding sarcomeric proteins.
The salient clinical and morphological features of the disease vary
according to the underlying genetic mutation. For example, marked
hypertrophy is common with beta-myosin heavy chain mutations whereas
mutations in troponin T may be associated with mild hyper-trophy but a
high risk of sudden death. Modifying
genetic factors may also influence the phenotype in HCM. These include
polymorphisms of components of the renin-angiotensin-aldosterone
system which influence myocyte growth.
The hypertrophy may not manifest before completion of the adolescent
growth spurt, making the diagnosis in children difficult. HCM due to
myosin-binding protein C may not manifest until the sixth decade of life
or later.
Sporadic cases of HCM occur, but the aetiology is unknown. HCM may
also be associated with Noonan's syndrome, Friedreich's ataxia, glycogen
storage disease,
and mitochondrial myopathies.
Clinical features
Patients with HCM present with chest pain, dyspnoea, syncope or
presyncope (typically with exertion), cardiac arrhythmias and sudden
death. Sudden death may occur at any age but the highest rates (up to 6%
per annum) occur in adolescents or young adults. Risk factors for sudden
death are discussed below. Dyspnoea is common and is due to impaired
relaxation of the heart muscle. Left ventricular
filling - and therefore left ventricular emptying - is impaired,
compounded by outflow obstruction in about one-third of cases. Systolic
ventricular function
remains good until the very late stages of disease when progressive
dilatation may occur. Atrial fibrillation occurs (the prevalence increasing
with increasing duration of disease) and is associated with worsening
symptoms due to reduction in ventricular filling and an increased risk of
stroke.
The classic physical findings are:
■double apical pulsation (forceful atrial contraction producing a fourth
heart sound)
■jerky carotid pulse because of rapid ejection and sudden obstruction to
left ventricular outflow during systole
■ejection systolic murmur due to left ventricular outflow obstruction late
in systole - it can be increased by manoeuvres that decrease afterload, e.g.
standing or Valsalva, and decreased by manoeuvres that increase afterload
and venous return, e.g. squatting
■pansystolic murmur due to mitral regurgitation {secondary to systolic
anterior motion (SAM)}
■fourth heart sound (if not in AF).
Investigations
■ ChestX-ray is usually unremarkable.
■ECG demonstrates left ventricular hypertrophy and ST and T wave
changes. Abnormal Q waves, most commonly in the inferolateral leads
occur in 25-50%of patients.
■Echocardiogram is usually diagnostic and in the most typical cases
shows asymmetric left ventricular hypertrophy (involving septum more
than posterior wall), systolic anterior motion of the mitral valve, and a
vigorously contracting ventricle . However, any pattern of hypertrophy
may be seen, including concentric and apical hypertrophy. Certain
mutations, e.g. involving the troponin gene, are
associated with minimal or even no hypertrophy.
■Pedigree analysis generally reveals autosomal dominant inheritance
and may provide prognostic information (e.g. history of sudden death).
Genetic analysis where available confirms the diagnosis, may provide
prognostic information and facilitates evaluation of relatives.
■Exercise testing and ambulatory ECG recording also provide
prognostic information.
Treatment
The overriding concern in the management of HCM is the prevention of
sudden death. Several risk factors for sudden death have been identified.
Massive left ventricular hypertrophy (> 30 mm) is a recognized risk
factor but the majority of sudden deaths do not occur in individuals with
massive hypertrophy, and other risk
factors must be considered. These include genotype, family history of
sudden cardiac death, abnormal blood pressure response during exercise,
non-sustained ventricular tachycardia on Holter monitoring and recurrent
syncope. The presence of two or more of these risk factors is associated
with a substantial risk of sudden death.
Implantable defibrillators effectively prevent sudden death in high-risk
cases. In patients in whom the risk is less high, amiodarone is an
appropriate alternative.
Recent research has suggested that microvascular dysfunction as assessed
by PET scanning may be an independent risk factor for sudden death but
this requires
further validation.
Chest pain and dyspnoea are treated with betablockers and verapamil,
either alone or in combination. If these are ineffective, disopyramide is a
useful second-line
therapy for patients with obstruction. In selected cases only (e.g. elderly
patients) with significant left outflow obstruction and recalcitrant
symptoms, dual-chamber
pacing may be of use. Alcohol (non-surgical) ablation of the septum has
been investigated and appears to give good results in reduction of outflow
tract obstruction and subsequent improvement in exercise capacity. There
are, however, significant risks, including the development of complete
heart block and massive myocardial infarction. Occasionally, surgical
resection of septal myocardium
may be indicated. Vasodilators should be avoided because they may
aggravate left ventricular outflow obstruction or cause refractory
hypotension.
Restrictive cardiomyopathy
Some cardiomyopathies do not present with muscular hypertrophy or
ventricular dilatation. Instead, the
ventricular filling is restricted (as
with constrictive
pericarditis), resulting in symptoms and signs of heart failure. Dilatation
of the atria and thrombus formation commonly occur.
Conditions associated with this form of cardiomyopathy include
amyloidosis (commonest), sarcoidosis, Loeffler's endocarditis and
endomyocardial fibrosis; in the latter two conditions there is myocardial
and endocardial fibrosis associated with eosinophilia. The idiopathic form
of restrictive cardiomyopathy may be familial and has been associated
with mutations in the sarcomeric protein troponin I, suggesting that this
form may be part of the spectrum of hypertrophic cardiomyopathy.
Clinical features
Dyspnoea, fatigue and embolic symptoms are the presenting features.
Restriction to ventricular filling (especially right) results in persistently
elevated venous pressures, consequent hepatic enlargement, ascites, and
dependent oedema.
Physical signs are similar to those of constrictive pericarditis - a high
jugular venous pressure with diastolic collapse (Friedreich's sign) and
elevation of venous pressure with inspiration (Kussmaul's sign). A fourth
heart sound is common in early disease and cardiac enlargement, and a
third heart sound may be present in advanced disease. In idiopathic
restrictive cardiomyopathy, however, cardiac size may remain normal
Investigations
■ Chest X-ray may show pulmonary venous congestion.
The cardiac silhouette can be normal or show cardiomegaly and/or atrial
enlargement.
■ ECG usually has low-voltage and ST segment and T wave
abnormalities.
■ Echocardiogram shows symmetrical myocardial thickening and often
a normal systolic ejection fraction, but impaired ventricular filling.
■ Cardiac catheterization and haemodynamic studies help distinction
from constrictive pericarditis.
■ Endomyocardial biopsy in contrast with other cardiomyopathies
is often useful in this condition and may permit a specific diagnosis such
as amyloidosis to be made.
Treatment
There is no specific treatment. Cardiac failure and embolic manifestations
should be treated. Cardiac transplantation should be considered in some
severe cases,
especially the idiopathic variety. In primary amyloidosis, combination
therapy with melphalan plus prednisolone with or without colchicine may
improve survival. However, patients with cardiac amyloidosis have a
worse prognosis than those with other forms of the disease, and the
disease often recurs after transplantation. Liver transplantation may be
effective in familial amyloidosis (due to production of mutant prealbumin)
and may lead to reversal of the cardiac abnormalities.
Arrhythmogenic right ventricular cardiomyopathy
Arrhythmogenic
right
ventricular
cardiomyopathy
(ARVC)
is
characterized by progressive fibrofatty replacement of the right
ventricular myocardium .
This leads to ventricular arrhythmia and risk of sudden death in its early
stages and right ventricular or biventricular failure in its later stages. It is
familial in at least 50% of cases
Clinic al features
Presentation is most commonly with severe symptomatic ventricular
arrhythmias or syncope. Occasionally presentation is with right heart
failure. Heart failure, however, is more commonly associated with a later
stage of disease, in which left ventricular dilatation may also occur, and
severity of arrhythmia may paradoxically diminish. The condition is often
asymptomatic and the first presentation
may be with sudden death or alternatively it may be diagnosed as a result
of routine medical evaluation or family screening.
Investigations
■ Chest X-ray is usually unremarkable except in advanced disease.
■ECG most commonly demonstrates T wave inversion in precordial
leads related to the right ventricle dilatation
may be present .
Incomplete or complete RBBB is seen.
■Echocardiogram. In early cases this is often normal and in more
advanced cases may demonstrate right ventricular dilatation and
aneurysmformation, associated in some cases with concomitant left
ventricular dilatation.
■MRI demonstrates morphological abnormalities of the RV and is
capable of demonstrating fatty infiltration.
■RV angiography demonstrates enlargement and abnormal motion of
right ventricular myocardium.
■RV biopsy may demonstrate fibrofatty replacement but is often falsely
negative.
■Holter monitoring often demonstrates frequent extrasystoles of right
ventricular origin and runs of nonsustained or sustained ventricular
tachycardia.
■Genetic testing, although currentlyin its infancy,may be a vital
diagnostic tool, particularly in variably penetrant disease.
Treatment
Beta-blockers
are
first-line
treatment
for
patients
with
non-life-threatening arrhythmias. Amiodarone or sotalol may be used for
symptomatic arrhythmias, and for refractory or life-threatening
arrhythmias an ICD may be required.Occasionally cardiac transplantation
is indicated, either for intractable arrhythmia or cardiac failure.