MYOCARDIAL ANDENDOCARDIAL DISEAS ATRIAL MYXOMAThis 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 or are part of a multiple system syndrome. 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 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 space occupying 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 DISEASEMyocardial 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).
MyocarditisAcute inflammation of the myocardium has many causes. Establishment of a definitive aetiology with isolation of viruses or bacteria is difficultIn 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 myocarditisIdiopathicInfective Viral: Coxsackie virus, adenovirus, CMV, echovirus, influenza, polio, hepatitis, HIVParasitic: 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), leptospirosisFungal RickettsialToxicDrugs Causing hypersensitivity reactions, e.g. methyldopa, penicillin, sulphonamides, antituberculousRadiation May cause myocarditis but pericarditis more commonAutoimmune An autoimmune form with autoactivated T cells and organ-specific antibodies may occur
Clinical featuresMyocarditis 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.■ECG demonstrates ST andT wave abnormalities and arrhythmias. Heart block maybe seen with diphtherimyocarditis, Lyme disease and Chagas' disease ■ Cardiac enzymes are elevated.■Viral antibody titres may be increased. Howeverdiagnosis depends on the demonstration of acutely rising titres.■Endomyocardial biopsy may show acute 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.
TreatmentThe underlying cause must be identified, treated, eliminated. 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 . Antibiotics should be administered 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. 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 . Novel and effective antiviral, immunosuppressive (e.g. gamma-interferon) and intmunomodulating (e.g. IL-10) agents are currently undergoing
Giant cell myocarditisThis is a severe form of myocarditis characterized by the presence of multinucleated giant cells within the myocardium. The cause is unknown but it maybe associated with sarcoidosis, thymomas and autoimmune disease. It has a rapidly progressive course and a poor prognosis. Immunosuppression is recommended.Chagas' diseaseChagas' 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.
CARDIOMYOPATHYCardiomyopathy 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-specificautoantibodies.
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 cardiomyopath Inflammatory Post-infective, autoimmune, connective tissue diseases (systemic lupus erythematosus, systemic sclerosis)Metabolic e.g. glycogen storage diseasesNutritional Thiamin, selenium deficiencyEndocrine Acromegaly, thyrotoxicosis, myxoedema, diabetes mellitusInfiltrative Hereditary haemochromatosisNeuromuscular e.g. muscular dystrophy, Friedreich's ataxia, mitochondrial myopathiesToxic Alcohol, cocaine, doxorubicin, cyclophosphamide, cobaltHaematological Sickle cell anaemia, thrombotic thrombocytopenic purpura
Clinical featuresPresentation 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
TreatmentThe 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 contribute 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.
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 featuresPatients 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. 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 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. ■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.
TreatmentThe 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 family history of sudden cardiac death abnormal blood pressure response during exercise,non-sustained ventricular tachycardia on Holter monitoring 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.
Chest pain and dyspnoea are treated with betablockers and verapamil, either alone or in combination. If these are ineffective, disopyramide is a useful second-linetherapy 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 myocardiummay be indicated. Vasodilators should be avoided because they may aggravate left ventricular outflow obstruction or cause refractory hypotension.
Restrictive cardiomyopathySome cardiomyopathies do not present with muscular hypertrophy or ventricular dilatation. Instead, the ventricular filling is restricted (as with constrictivepericarditis), 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 featuresDyspnoea, 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
TreatmentThere 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 cardiomyopathyArrhythmogenic 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 casesClinic al featuresPresentation 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 presentationmay 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.■Signal averaged ECG may indicate the presence of late potentials, the delayed depolarization of individual muscle cells.■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
TreatmentBeta-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.