Cardiology - Myocardial disease

Question 1

What is brown atrophy?

Answer 1

The myocardium is subject to various degenerations and infiltrations. Brown atrophy is a phenomenon of unknown aetiology but is frequently associated with wasting diseases and old age.

The heart appears small and the surface wrinkled, with loss of epicardial fat, tortuous coronary vessels and brown friable muscle.

Question 2

What is cloudy swelling?

Answer 2

This is another degenerative change that affects the myocardium. Infections and many toxic states - e.g. typhoid, influenza, sepsis etc cause a soft, pale and friable myocardium. Microscopically, the muscle fibres are swollen with granular fragmentation of the cytoplasmic mitochondria.

Question 3

Fatty infiltration

Answer 3

This is increased epicardial deposition of fat associated with generalized adiposity. This may extend into the fibrous septa and between the muscle fibres, but the myocardial fibres are normal.

Question 4

What is fatty degeneration?

Answer 4

This represents damage to myocardial cells, as a result of which there is accumulation of fatty material within the cell cytoplasm. It may be due to any of the causes of cell damage.

There is pale mottling of the muscle, particularly of the subendocardial fibres and especially in the left ventricle - “thrush breast” or “tabby cat” appearance. There are fine fatty droplets in the muscle fibres, most marked in those situated furthest from the blood vessels and therefore at sites of maximal anoxia.

Question 5

What is meant by the term cardiomyopathy?

Answer 5

Cardiomyopathy means disease of heart muscle and refers to a heterogeneous group of disease each of which may present as different syndromes but which have in common abnormality in structure and or function of the myocardium. Generally, the term excludes disease of the heart due to hypertension, coronary insufficiency, valvular malfunction or rheumatism (which is a pancarditis).

They can present in families or be sporadic. The cardiac lesion may be the only abnormality or many other systems may be affected. There are many aetiologies but 3 distinct patterns of myocardial abnormality are recognised - dilated, hypertrophic and restrictive.

Question 6

What is dilated cardiomyopathy?

Answer 6

This is a functional abnormality of the myocardium causing poor systolic contraction and with dilatation of the ventricular cavities associated with reduced wall thickness. Mural thrombus in ventricles and atrial appendages is also frequency seen.

Question 7

What is the microscopic appearance of dilated cardiomyopathy?

Answer 7

There is a non specific rather diffuse interstitial fibrosis with tiny foci of individual cell necrosis with a localised and slight inflammatory response.

Question 8

What is the pathogenesis of dilated cardiomyopathy?

Answer 8

This is the end stage of myocardial damage for many causes including:

• Idiopathic (no clear cause)
• Genetic mutation - Duchenne muscular dystrophy, haemochromatosis
• Alcohol abuse
• Infections - Coxsackievirus B virus (causes viral myocarditis) and Chagas disease (protozoal)
• Chemotherapy - doxorubicin, adriomycin
• Wet beri beri (thiamine deficiency)
• Peripartum cardiomyopathy (3rd trimester –> weeks after delivery)
• Thyrotoxicosis

Question 9

What is the presentation of dilated cardiomyopathy?

Answer 9

Fatigue, dyspnoea, pulmonary oedema, RVF, emboli, AF or VT (cardiac arrest).

Question 10

Signs of dilated cardiomyopathy

Answer 10

Tachycardia
Decreased BP
Raised JVP
Displaced, diffuse apex
S3 gallop (blood hits dilated ventricular wall during diastole)
Mitral or tricuspid regurgitation
Pleural effusion
Jaundice
Hepatomegaly
Ascites

Question 11

What tests can aid in the diagnosis of dilated cardiomyopathy?

Answer 11

There is no one single diagnostic test for dilated cardiomyopathy, the following are helpful:

• Bloods: BNP is a sensitive and specific markers in diagnosing heart failure, HYPOnatraemia indicates a poor prognosis
• CXR: cardiomegaly, pulmonary oedema
• ECG: tachycardia, non specific T wave changes, poor R wave progression
• Echo: globally dilated hypokinetic heart and low ejection fraction (look for mitral, tricuspid and mural thrombus)

Question 12

How is dilated cardiomyopathy treated?

Answer 12

Bed rest, diuretics, digoxin, ACE-i, anticoagulation, biventricular pacing, ICDs, cardiac transplantation.

Mortality is variable, e.g. 40% in 2 years.

Question 13

What is hypertrophic cardiomyopathy? Briefly outline the pathophysiology

Answer 13

In this form of cardiomyopathy, systolic function is hyperkinetic because new sarcomeres are added in parallel to existing ones. There is marked reduction in systolic volume because of a reduction in ventricular chamber size and difficulty in diastolic filling due to reduced compliance.

Both of these lead to impaired ventricular filling and reduced stroke volume (by Starlings law) leading to diastolic heart failure. The LV outflow tract (LVOT) is obstructed from asymmetric septal hypertrophy compared to the free wall. A narrowed LVOT increases blood velocity through the tract by the Venturi effect which pulls the anterior leaflet of the mitral valve towards the septum, further obstructing blood. This produces a crescendo decresencdo murmur (similar to aortic stenosis).

Question 14

What are the pathological features of HCM?

Answer 14

Macroscopically, the ventricular wall appears grossly thickened and weight is increased. The thickening may be septal, bilateral or unilateral, symmetrical or asymmetrical. There may appear to be obstruction to the outflow tract by muscle bulk.

There are consistent a fairly specific histological abnormalities with interstitial fibrosis and a whorling or mal-arrangement of myocardial fibres.

Question 15

What are the signs of HCM?

Answer 15

Crescendo decrescendo murmur (loudest on Valsalva manouvre) 
Bifid pulse (2 pulses caused by the mitral valve moving towards the outflow tract and causing increased obstruction during systole)
S4 sound (atrial contraction pushing blood into non compliant wall)
Systolic thrill (palpable murmur) at lower left sternal edge

Question 16

Symptoms of HCM

Answer 16

Angina (due to myocardial ischaemia)
Palpitations (ischaemia to the conducting system)
Syncope
Dyspnoea
Sudden death (most common cause of sudden cardiac death in young adults)

Question 17

What is the aetiology of HCM?

Answer 17

Most often HCM is autosomal dominant where there is a missense mutation affecting the cardiac sarcomere. 70% have genes encoding beta myosin heavy chain, myosin binding protein C or troponin T. It may present at any age and is associated with other inherited conditions such as Freidrichs ataxia (itself an autosomal recessive condition).

Question 18

What investigations are useful in HCM?

Answer 18

1) ECG - LVH; progressive T wave inversion; deep Q waves; AF
2) Echo - asymmetrical septal hypertrophy; small LV cavity with hypercontractile wall; midsystolic closure of aortic valve; systolic anterior movement of mitral valve
3) Cardiac catheterisation - may provoke VT; helps assess severity of gradient, coronary artery disease or mitral regurgitation

Question 19

How is HCM treated?

Answer 19

• beta blockers or verapamil for symptoms (the aim is reducing ventricular contrctility)
• amiodarone for arrhythmias (AF, VT)
• anticoagulate for paroxysmal AF or systemic emboli
• surgery (septal myomectomy) is reserved for those with severe symptoms
• consider ICD

Question 20

What factors are associated with a poor prognosis of HCM?

Answer 20

Age < 14 years
Syncope at presentation
Family history of HCM/ sudden death

Question 21

What is restrictive cardiomyopathy?

Answer 21

Third subtype of primary cardiomyopathy. The ventricle is not hypertrophied by is stiff and less compliant. This impairs ventricular filling which decreases stroke volume by Starling’s law. Cardiac output falls and so restrictive cardiomyopathy causes diastolic heart failure.

Question 22

What are the causes of restrictive cardiomyopathy?

Answer 22

1) Amyloidosis
- Familial Amyloid Cardiomyopathy = mutant transthyretin (TTR) protein is misfolded and deposited in the myocardium (transthyretin transports thyroxine and retinol in the blood)
- Senile Cardiac Amyloidosis = accumulation of wild type transthyretin in myocardium

2) Cardiac sarcoidosis
3) Endocardial fibroelastosis
4) Loffler endo(myo)carditis - eosinophilic accumulation in the endocardium leading to inflammation and restricted filling
5) Haemachromatosis
6) Radiation

Question 23

How does restrictive cardiomyopathy present?

Answer 23

The presentation is similar to constrictive pericarditis. Right ventricular failure predominates, causing raised JVP with prominant x and y descents, hepatomegaly, oedema and ascites.

Question 24

What is endomyocardial fibrosis (EMF)?

Answer 24

This is another cause of restrictive cardiomyopathy that affects tropical and sub-tropical regions. In the acute form of the disease, thrombotic material is deposited on the endocardial surface and becomes organised. This leads to increasing fibrosis which starts at the apex and more upwards to involve the ventricular mural endocardium and atrioventricular valves.

There is a so called non tropical form which is due to systemic degranulation of eosinophils which produces an endocardial damaging factor. Tropical EMF has no association with eosinophilia but the findings in the heart are the same.

Question 25

What is endocardial fibroelastosis?

Answer 25

This is a primary condition that usually affects children in which characteristically shows endocardial thickening in the left atrium and ventricle with a smooth glossy surface. Histologically, the tissue shows increased amounts of collagen. Some causes may be due to foetal viral infection but otherwise the aetiology is unknown. Secondary fibroelastosis occurs in left sided congenital heart defects.

Question 26

How is restrictive cardiomyopathy diagnosed?

Answer 26

The ECG in these patients often shows low voltage QRS complexes, but cardiac catheterisation can also be used.

Question 27

How is restrictive cardiomyopathy treated?

Answer 27

Treat the underlying cause! But many patients will require heart transplant.

Question 28

What is myocarditis?

Answer 28

This is the presence of inflammatory cells in the myocardium. Clinical features are due to ventricular electrical irritability with rhythm and conduction abnormalities.

Four presentations occur:

1) Fulminant myocarditis
2) Acute myocarditis
3) Chronic active myocarditis
4) Chronic persistent myocarditis

Question 29

What causes myocarditis?

Answer 29

The causes of myocarditis can be grouped as follows:

1) Toxic or metabolic damage
2) Microbial organisms
3) Sarcoidosis
4) Rheumatic fever (pancarditis)
5) Giant cell myocarditis

Question 30

What toxins can cause myocarditis?

Answer 30

There are many causes for toxic and metabolic damage to the myocardium, including:

• typhoid fever
• streptococcal infections (esp group A beta haemolytic)
• diphtheria
• poisons - arsenic, phosphorus, chloroform
• metabolic abnormalities - hypokalaemia and hyperkalaemia, magnesium deficiency, catecholamine excess

In all of these conditions the main histological feature is focal necrosis of myocardial cells and an inflammatory cell infiltrate is not very marked.

Question 31

What microbial organisms caused myocarditis?

Answer 31

1) Pyogenic bacteria: suppurative myocarditis is rare except as a terminal event in debilitating illness or immune deficiency states complicated by septicaemia
2) Viruses: Coxsackie virus infections are the best documented both as sporadic fatal cases and in known epidemics, especially neonates. Other viruses causing myocarditis are poliomyelitis, mumps and ECHO
3) Protozoa: of importance are toxoplasmosis, usually as a congenital infection in the neonatal period and in South America Chaga’s disease due to Trypanosoma cruzi
4) Syphilis: aortitis causes aneurysm and aortic valve incompetence. Gummas affecting the myocardium, particularly the conducting system in the upper interventricular septum

Question 32

What is giant cell myocarditis?

Answer 32

This is an acute fulminating form of fatal acute myocarditis with foci of necrosis at the margins of which there are numerous elongated multinucleated cells. Whether these cells are of myocardial or histiocytic origin is debatable. The pathogenesis is unknown.

Question 33

What is fulminant myocarditis?

Answer 33

One of the four distinct clinical syndromes of myocarditis. This follows a viral prodrome or influenza like illness, and results in severe heart failure or cardiogenic shock.

Question 34

Acute myocarditis

Answer 34

This presents over a longer period with heart failure, and can lead to dilated cardiomyopathy.

Question 35

What is chronic active myocarditis?

Answer 35

This is rare and associated with chronic myocardial inflammation.

Question 36

Chronic persistant myocarditis

Answer 36

Is characterised by focal myocardial infiltrates and can cause chest pain and arrhythmia without necessarily causing ventricular dysfunction.

Question 37

What investigations are useful in myocarditis?

Answer 37

ECG changes are common but non specific. Biochemical markers of myocardial injury (e.g. troponin I and , creatinine kinase) may be elevated in the early phase. Echo may reveal left ventricular dysfunction that is sometimes regional (due to focal myocarditis) and cardiac MRI may show diagnostic patterns of myocardial inflammation or infiltration. Biopsy is sometimes used to confirm the diagnosis.

Question 38

How is myocarditis managed?

Answer 38

In most patients myocarditis is self limiting and the immediate prognosis is good. However, death may occur due to ventricular arrhythmia or rapidly progressive heart failure. Some forms of myocarditis may lead to chronic low grade myocarditis or dilated cardiomyopathy - e.g. in Chaga’s disease the patient frequently recovers from an acute infection but goes on to develop a chronic dilated cardiomyopathy.

There is no evidence for any benefit from treatment with corticosteroids and immunosuppressive agents.