Cardiomyopathy

Introduction

Cardiomyopathy is a term used to describe a heart muscle disorder, without another obvious cardiac abnormality. The European Heart Journal describes it as a:

myocardial disorder in which heart muscle is structurally and functionally abnormal without coronary artery disease, hypertension, valvular or congenital heart diseases.

However, sometimes cardiomyopathy is a result other cardiac disease, such as hypertension, valvular disorders or ischaemic heart disease.

There are many types of cardiomyopathy, with varying prognoses, from asymptomatic to severe life-limiting and life-threatening. Some types are associated with sudden cardiac death.

The main three types are:

• Dilated cardiomyopathy
• Hypertrophic cardiomyopathy
• Restrictive cardiomyopathy

Epidemiology

• Cardiomyopathies can at a younger age than most other cardiac diseases
• Suspect cardiomyopathy in any patient presenting with heart failure
• Hypertrophic cardiomyopathy is the most common cause of unexpected death in childhood
• Often a genetic component – especially for hypertrophic cardiomyopathy – in which 50% of cases have a family history

Classification and causes

Cardiomyopathies can be primary (idiopathic) and secondary. Secondary causes include:

• Connective tissue disorders – e.g. sarcoidosis, SLE
• Endocrine disorders – e.g. diabetes, thyroid disease, acromegaly
• Drugs – e.g. chemotherapeutic agents, cocaine, alcohol
• Infection
• Nutrition – obesity, some specific deficiencies – e.g. vit B1, calcium, magnesium
• Genetic causes – e.g. duchenne muscular dystrophy

Clinically, we divide cardiomyopathies into 4 types:

• Dilated cardiomyopathy
• Hypertrophic cardiomyopathy
• Restrictive cardiomyopathy
• Arrhythmogenic right ventricular cardiomyopathy (ARVC)

Dilated cardiomyopathy (DCM)

The most common type of cardiomyopathy. It is characterised by enlarged ventricular size, with normal ventricular wall thickness, and systolic dysfunction. Usually affects the left or both ventricles. It is the most common indication for heart transplant.

Epidemiology

• Affects about 2 in 10,000
• Often in a genetically susceptible individual
• Typically presents in adults aged 20-60
• More common in men
• More common in Africans

Causes

Identifying an underlying cause is difficult. Patients often have multiple risk factors.

• Ischaemic heart disease
• Alcohol
• Cocaine use
• Thyroid disorder
• Valvular disease
• Genetic causes
• Sometimes idiopathic
• Infective causes
  • Bacterial
  • HIV
  • Viral – e.g. coxsackie viruses, or a viral myocarditis
  • Other
• Autoimmune, connective tissue and granulomatous disorders
• Drugs
• Peripartum (around pregnancy)
  • Associated with a particularly poor prognosis

For prevention purposes – avoiding alcohol and cocaine use is advisable

Pathophysiology

• It is believed that after damage to the myocardium, some of the myocardial cells undergo necrosis, and there is a chronic fibrosis. The remaining myocardial tissue then dilates and hypertrophies to compensate
• This often leads to mitral or tricuspid regurgitation
• Atrial fibrillation (and other arrhythmias – particularly AV node block) can occur as a result of atrial dilatation
• Thrombus formation can occur in the large dilated chambers
• The onset is usual gradual, except in cases where na acute myocarditis is the cause

Presentation

The typical presentation is that of of heart failure

• Dyspnoea – particularly on exertion
• Fatigue
• Peripheral oedema
• Raised JVP (if right ventricle involved)
• Loud 3rd and 4th heart sounds

It may also present as:

• Arrhythmia – e.g. atrial fibrillation, or AV node block
• Thomboembolism (e.g. stroke or PE)
• Acute myocarditis

Investigations

ECG changes may include:

• Sinus tachycardia
• T wave inversion and Q waves (even if no previous MI)
• ST-depression (non-specific pattern)
• Left bundle branch block

Chest x-ray

• May show an enlarged heart
• Signs of heart failure
• Pleural effusion

Echocardiogram

• Shows dilated, hypo kinetic chambers
• Also useful to rule out primary valve disorders
• May be able to detect a mural thrombus

Coronary angiogram may be considered when there is doubt over the diagnosis (vs ischaemic heart disease) or iscahemic heart disease is suspected as the cause.

Cardiac muscle biopsy

• Only rarely performed, but may be considered if a specific cause (e.g. myocarditis, amyloidosis, sarcoidosis) is suspected

Management

• Treat any reversible causes, e.g.:
  • Toxoplasmosis
  • Haemochromatosis
  • Thyrotoxicosis
• Prophylactic anticoagulation
  • Warfarin or NOAC
• Treat any arrythmia
• Consider pacemaker for AV node block
  • Be aware that in acute myocarditis this may resolve spontaneously and permanent pacemaker may not be required
• Otherwise, treat as for heart failure:
  • ACE-inhibitors
    • Consider ARB if intolerant of ACE-i
  • +/- Beta-blockers
  • Diuretics
    • Loop and thiazide diuretics should be given to all symptomatic patients
    • Spironolcatone has been shown to improve survival
  • Nitrates
• Consider an implantable cardioverter defibrillator (ICD) – patients are at high risk of arrhythmia
• Consider heart transplant
  • Younger patients (age <60) typically have priority
  • Hearts available for transplant are scarce
  • Heart transplant has relatively good outmodes – with about 70% 5-year survival

Prognosis

• Prognosis is extremely poor
• Progression of the disease results in worsening heart failure
• 70% mortality with 5 years
• Death is often sudden due to thrombus formation, or sudden arrhythmia
• Prognosis worse if:
  • Ventricular wall is thin
  • Ventricles markedly dilated
• Prognosis is better if:
  • Ventricular wall maintains normal thickness
  • Less dilated

Hypertrophic cardiomyopathy (HCM)

Hypertrophic cardiomyopathy (sometimes also hypertrophic obstructive cardiomyopathy – HOCM) is an autosomal dominant genetic disorder, which typically causes diastolic dysfunction, with or without outflow obstruction.

In HCM, there is hypertrophy of the left ventricle, which causes left ventricular outflow obstruction, mitral valve problems, myocardial ischaemia and increases the risk of tachyarrhythmias.

It is a relatively common cause of sudden death in young athletes, and may also cause unexplained syncope – particularly associated with exercise.

It is diagnosed by echocardiogram. Treatment usually consists of beta-blockers and calcium channel blockers (particularly verapamil). Occasionally, surgery may be performed to reduce outflow tract obstruction.

Epidemiology

• Most common genetic cardiac disease
• Prevalence 1 in 500
• More common in men
• More common in black people
• The obstructive form accounts for 25% of cases
• The most common cause of sudden cardiac death in young people
• Typically presents between ages of 20 – 40

Aetiology

• Autosomal dominant genetic disorder – but has variable penetrance and expressivity
• A mutation in any one (or more) of up to 12 genes that code for cardiac proteins can cause the disease
  • Troponin T mutations are the most significant. They are more likely to cause sudden cardiac death and often this occurs without any left ventricular hypertrophy (LVH)

Pathophysiology

• Genetic defects in the genes that code for cardiac protiens – such as beta-myosin heavy chain gene, troponin and alpha-tropomyosin
• This results in a disorganised cardiac matrix, and left ventricular hypertrophy
• Hypertrophy can occur in any part of the left ventricle, but most commonly it affects the anterior ventricular septum

Presentation

• Most cases are asymptomatic
• Dyspnoea
• Chest pain
• Syncope (especially on exercise)
  • Both syncope and dyspnoea may be initiated by alcohol
  • Always investigate unexplained syncope in young athletes
• Palpitations
• Sudden death
  • Can be due to arrhythmia or due to outflow tract obstruction
  • Unexplained syncope is a risk factor for sudden death
• Family history of HCM
• Aortic stenosis and coronary artery disease may present similarly

Examination

Can be normal. Abnormal findings might include:

• Forceful apex best
• Late ejection systolic murmur, exacerbated by valuable manoeuvre, reduced when squatting
  • Does NOT radiate to the neck
  • Best heard at left sternal edge, 3rd-4th intercostal space
• Prominent JVP a wave
• Abnormal blood pressure response to exercise
  • Normally systolic BP rises by 20-25mmHg
  • In HCM it rises less than this, or may even fall
• Atrial fibrillation
  • Occurs in 20% of patients
  • Background AF rate in general population is 5%

Investigations

ECG

• Changes typically non-sepcific
• ST-segment changes
• T-wave inversion
• Signs of LVH
  • Be aware that voltage criteria for LVH are not specific and often seen in normal young healthy adults
• Atrial fibrillation in 20% of patients

Echo

• This is the standard diagnostic test
• Asymmetric septal hypertrophy >15mm
• Ratio of septal wall to posterior wall > 1.4:1
• Non-dilated left ventricular cavity
• Normal systolic function
• Absence of valvular disease

CXR

• Often normal
• Heart size may be normal or enlarged
• Left atrial enlargement may be seen in cases of mitral regurgitation

Cardiac MRI

• May be superior to MRI for assessing segmental hypertrophy
• Can also assess systolic and diastolic dysfunction

Other investigations

• Myocardial biopsy may be used to rule out other conditions
• Cardiac catheterisation – may be used to assess the degree of outflow obstruction and other structural abnormalities

Management

Management aims to reduce the symptoms and progression of the disease.

• Control arrhythmia – typically with anti-arrhythmic drugs
  • Arrhythmias caused by HCM may be more amenable to ablation therapy than arrhythmias of other causes
• Anticoagulation for atrial fibrillation
• Reduce outflow tract obstruction gradient, and improve diastolic function
  • Beta-blcokers
  • Verapmil
    • Disopyramide is added to the beta-blocker + verapamil combination in severe cases. It is negatively inotropic
  • These drugs reduce cardiac contractility, and thus dilate the hypertrophied left ventricle, reduce outflow tract obstruction and improving diastolic function
  • These drugs improve the physical functioning of the heart muscle but do not have a significant effect on arrhythmias
  • BEWARE of drugs that reduce preload, as these decrease the chamber size and exacerbate symptoms. These include:
    • ACE inhibitors, ARBs, nitrites and diuretics
    • This is a major difference between management of DCM and HCM
• Implantable cardioverter defibrillator should be consider for those at high risk of sudden death
• Avoidance of competitive sports and strenuous exercise
• Surgical myectomy
  • Patients with symptoms resistant to medical management should be considered for resection of the hypertrophied muscle to reduce the outflow tract obstruction
• Heart transplant should be considered in severe heart failure

Prognosis

• Annual mortality risk is 1-3%
  • Higher risk if younger age at presentation
• Sudden death is the most common cause of death in HCM
• It typically occurs in young patients, with few or no symptoms
• Risk factors for sudden death include:
  • Unexplained syncopal events
  • Episode of ventricular fibrillation or ventricular tachycardia
  • Abnormal blood pressure response to exercise
  • FHx of sudden cardiac death
  • Age <30
• ICDs are effective at preventing sudden death in HCM
  • Consider use as secondary prevention in any patient who has had a cardiac arrest or previous episode of sustained VT
• Patients with LVH wall thickness of <20mm and no other risk factors are low risk and have a similar life expectancy to the general population
• The risk of infective endocarditis is low – routine antibiotic prophylaxis is NOT recommended

Restrictive cardiomyopathy (RCM)

Restrictive cardiomyopathy is the least common of the three types discussed here. It accounts for about 5% of all cases of cardiomyopathy. It is due to reduced compliance of the ventricular walls during diastolic filling. It can broadly be divided into two type:

• Those where there is infiltration of the myocardium by an invasive substance (e.g. amyloid plaques, sarcoidosis or iron in haemochromatosis)
• Fibrotic myocardium – without an external invasive substance

It most commonly affects the left ventricle, but can often affect both. The condition causes high diastolic filling pressures, which leads to pulmonary hypertension. It is also commonly associated with mural thrombi.

Epidemiology

• Most patients are elderly
• M:F is about the same
• Not usually inherited in a familial pattern
• Heart transplant is often indicated
• More prevalent in tropical regions

Aetiology

• Usually no underlying cause is identified
• Löfflers syndrome
  • Tropical disease
  • Starts with arteritis which spreads to cause thrombus formation not he endocardium and valves, ultimately leading to fibrosis
• Amyloidosis is the most common cause in the western world
• Sarcoidosis
• Haemochromatosis

Presentation

• Signs of heart failure
  • Dyspnoea – particularly exertional
  • Orthopnoea
  • Fatigue
  • Pulmonary oedema
  • Loud 3rd heart sound
• Heart size may be normal or enlarged
• Features of right ventricular failure may be present
  • Raised JVP
  • Hepatomegaly
  • Oedema
  • Ascites
• Presentation is similar to constrictive pericarditis
• AF develops in 75% of patients
• Other arrhythmias – including AV node block, and those of atrial and ventricular origin

Investigations

ECG

• Non-specific T wave and ST changes
• Pathological Q waves, in the absence of previous MI
• LVH

CXR

• Heart size is often normal, or even small
• May be enlarged in late stage amyloidosis or haemochromatosis

Echo

• Normal systolic function
• Dilated atria may be present
• Myocardial hypertrophy may be present (increased wall thickness)
• Helps to differentiate from restrictive pericarditis
  • This would show thickened pericardium

Prognosis

• Aim to treat the underlying cause. Early treatment for any of the major underlying causes may reduced disease progression
  • Haemochromatosis
  • Löffler’s syndrome
  • Amyloidosis
• Prognosis is poor – similar to DCM
  • 30% 5 year survivial
• For most patients there are no effective treatments that alter the cause of the disease
• BEWARE of diuretics
  • They reduce preload, and the stiff ventricles rely on preload for filling
• BEWARE of digoxin
  • Amyloidosis patients often have extreme digoxin sensitivity and can become easily toxic
• BEWARE of nitrites
  • They can reduce after load and cause dangerous hypotension
• There are no specific cardiac medical treatments for restrictive cardiomyopathy
• Some cases may be suitable for endocardial resection
• Heart transplant

Differential Diagnosis of Cardiomyopathy

• Ischaemic heart disease
• Valvular heart disease – particularly of the mitral and aortic valves
• Athletes
  • May produce some findings consistent with a cardiomyopathy, when in fact none is present
• Pericarditis
• Pulmonary stenosis
• VSD

Comparison Table

	Dilated	Hypertrophic	Restrictive
Pathology	Systolic dysfunction	Diastolic Dysfunction +/- outflow obstruction	Diastolic Dysfunction
Examination	Signs of LV +/- RV failure Cardiomegaly	Exertional dyspnoea, SOB and angina Ejection murmur 3rd and 4th heart sounds Sudden death	Exertional dyspnoea Fatigue Signs of LV +/- RV failure
ECG	Non-specific T wave and ST changes Q waves	LVH Q waves Non-specific ST changes TWI	LVH Q waves Non-specific ST changes TWI
X-ray	Cardiomegaly	Usually normal	Usually normal
Echo	Dilated, hypokinetic +/- Mural thrombus	Hypertrophied left ventricle Mitral pathology	Increased wall thickness
Treatment	Treat any underlying cause Treat for heart failure Prophylactic anticoagulation Treat arrhythmia Consider for heart transplant	Beta-blockers Verapamil Dsopyramide All above reduce contractility Surgical myotomy Heart Transplant	Treat the underlying cause Some cases may be appropriate for endocardial resection Heart transplant
Prognosis	30% 5-year survival	Annual mortality 1-3% Higher risk if younger age of presentation	30% 5-year survival

References

• Dilated cardiomyopathies – patient.info
• Beers, MH., Porter RS., Jones, TV., Kaplan JL., Berkwits, M. The Merck Manual of Diagnosis and Therapy
• Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
• Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.

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