The Heart in Systemic Disease

The heart may be affected by diseases that affect the circulation and in doing so, they make greater demands upon the heart. Increased cardiac output is demanded by fever, severe anaemia, thyrotoxicosis and pregnancy. The last is a physiological condition and not a disease. Hypovolaemia will also stress the circulation and its pump. This article does not aim to examine primary diseases of the heart such as congenital heart disease but systemic diseases in which the heart may also be involved. The scope is such that frequent use will be made of links to other articles about those diseases.

This is a very common disease that affects us all to a variable extent as the years go by. It produces coronary artery disease that is the commonest cause of death in developed countries, as well as affecting many other arteries. Atherosclerosis is discussed in its own article.

Coronary arteries may be involved in Kawasaki disease and, very rarely, in late syphilis.

The association between coronary heart disease and diabetes is as well known. It is also well known to be associated with abnormalities of lipid metabolism including the metabolic syndrome.¹ Less well known is the strong relationship between CHD and rheumatoid arthritis.²

Hypertensive heart disease is less common now that hypertension is better diagnosed and more effectively treated. It can lead to left ventricular hypertrophy that carries a poor prognosis. There is evidence that ACE inhibitors and AT2 antagonists too, may be able to reverse this.³

Disease of the lungs can also lead to right ventricular hypertrophy and strain.

• COPD, including that due to the general disease of cystic fibrosis
• Recurrent pulmonary embolism
• Primary pulmonary hypertension

Rheumatic fever is now very uncommon in Western Europe, although it was frequent in the earlier part of the 20th century and is still seen in other parts of the world, especially Africa. A complication that is well known and develops some time after the infection, is disease of the mitral valve, the aortic valve, or both. This is usually mitral stenosis or aortic stenosis but mitral regurgitation or aortic regurgitation may occur alone or in combination.

It is less well appreciated that the acute disease is also associated with myocarditis. This myocarditis can be severe. A soft, rumbling, mid-diastolic murmur, called the Carey-Coombs murmur may be heard during active disease. Severe disease is associated with a greater risk of recurrence. The myocarditis leaves the heart weak for the rest of the patient's life and even in the absence of valvular disease, there should be cardiological follow up for life.

As rheumatic fever appears to be confined to history, at least in the UK, other causes of disease of heart valves take importance. Many are congenital heart disease.

• Ankylosing spondylitis may be associated with aortic regurgitation.
• Incompetent valves, including mitral valve prolapse may occur with a number of the hypermobility syndromes including Ehlers-Danlos syndrome, Marfan's syndrome, Downs' syndrome and joint hypermobility syndrome.
• Marfan's syndrome may cause aortic regurgitation and even aortic aneurysm at the root.
• Another cause of aneurysm of the proximal aorta with aortic regurgitation is tertiary syphilis.
• Heart valves may be affected in many systemic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid antibody syndrome, the seronegative spondyloarthropathies, the systemic vasculitides, and scleroderma.⁴

Any damage or abnormality of the heart or valves makes them susceptible to subacute bacterial endocarditis. Acute bacterial endocarditis can occur when drug addicts inject themselves with heavily infected material.

Acute pericarditis, chronic pericarditis and pericardial effusion are all described in articles of their own. They are often associated with systemic disease. These are often inflammatory diseases or infections. Constrictive pericarditis may impair adequate filling of the heart. Tuberculosis is one possible cause. Pericardial effusion can further constrict the heart and cause cardiac tamponade.

Primary disease of the heart muscle, rather than coronary artery disease, is called cardiomyopathy. Cardiomyopathy is discussed much more fully elsewhere. They may be primary or due to other disease. Ischaemic heart disease tends to affect older people and so where there is heart failure, arrhythmias or thromboembolism in a young person, cardiomyopathy should be suspected.⁵ Many systemic diseases may cause cardiomyopathy:
There may be infiltration of the myocardium:

• Sarcoidosis.
• Amyloidosis.
• In Wilson's disease there may be infiltration with copper.
• In haemochromatosis there is infiltration of the heart muscle with iron.
• Glycogen storage diseases can also cause infiltration.

Cardiomyopathy can result from poisons:

• Alcohol probably requires around 7 or 8 units a day for at least 5 years⁶ but is probably an underdiagnosed cause and may represent 30% of dilated cardiomyopathy.⁷ Women are susceptible at a lower dose than men.⁸ High consumption of alcohol also leads to hypertension.
• Cobalt was found to induce cardiomyopathy in heavy beer drinkers in the 1960s.⁹ It is no longer used in beer production.
• Cardiomyopathy may occur in patients on long term dialysis. Many substances have been implicated.¹⁰
• Cocaine
• Amphetamines
• Chemotherapy for malignancy

There are causes related to endocrine disease, infections and malnutrition:

• Endocrine disease
  • Acromegaly
  • Pheochromocytoma
  • Diabetes. The relationship between ischaemic heart disease and microalbuminuria is well established, especially in type 2 diabetes. Maternal diabetes can even have an adverse effect on the developing fetal heart.¹¹
  • Hyperthyroidism
  • Hypothyroidism
• Infections
  • Acute viral infection, especially Coxsackie B
  • South American Trypanosomiasis (Chagas' disease)
  • Hepatitis B
  • HIV infection.
  Nutritional
  • Starvation
  • Vitamin B1 deficiency as in wet beriberi

Cardiomyopathy can also occur and be the fatal outcome of myopathies, especially the two X-linked muscular dystrophies:

• Duchenne muscular dystrophy
• Becker muscular dystrophy

Various other systemic diseases that may affect the myocardium include:

• Systemic sclerosis may cause myocarditis or pericardial effusion.
• Rheumatoid arthritis can cause pericardial effusion, valvulitis and myocardial fibrosis.

Systemic lupus erythematosis is a multisystem disease that has its own article. It is associated with pericarditis, hypertension, an increased risk of coronary heart disease and a condition called Libman-Sachs endocarditis. This also has its own record. It is classically described as like a cluster of mulberries on the ventricular surface of the posterior leaflet of the mitral valve and found at postmortem. The leaflet and the chordae tendinae are often adherent to the endocardium of the ventricular wall.

The disease is often missed at echocardiography. The spectrum of the disease has changed since the original description as steroids and other treatment has changed the course of the disease and life expectation, whilst limited, is much higher than it was. The left side of the heart is affected more often than the right but even the endocardium can be affected. Regurgitation is more frequent than stenosis.

Libman-Sachs endocarditis is usually described with SLE but it can also occur in anti-phospholipid syndrome.

Cardiac tumours are uncommon. Primary malignancy of the heart is very rare.¹² Metastatic spread of malignancy is very rare as shown by unselected autopsy reports.¹³ The tumour most commonly implicated is malignant melanoma. However, large autopsy studies of patients with disseminated cancer showed intracardiac metastases in approximately 15%.¹⁴ These metastases are asymptomatic in the majority of cases. Tumours most likely to metastasise to the heart are malignant melanoma, leukemia, malignant germ cell tumors, and malignant thymoma. Although carcinoma of the lung and breast do not often metastasise to the heart, because of the very high numbers, they account for the greatest numbers of cardiac metastases. Carcinoma of the lung can also cause atrial fibrillation. Intracardiac metastases are more often on the right side of the heart.

The most common clinical presentation is from pericardial effusion, tachy-arrhythmias, atrioventricular block, and congestive heart failure.

• ECG abnormalities and rhythm disorders often occur in patients with subarachnoid haemorrhage, and in cases of ischaemic stroke, intracranial haemorrhage, head trauma, neurosurgical procedures, acute meningitis, intracranial space-occupying tumours, and epilepsy.
• New-onset atrial fibrillation has been reported in up to one third of patients with acute stroke.

Abnormalities of renal function may affect the heart in a number of ways.

• Renal inadequacy may impair the clearance of drugs that are potentially cardiotoxic such as digoxin.
• Upset of electrolytes may cause cardiac abnormalities. Hypokalaemia, hyperkalaemia, hypercalcaemia and hypocalcaemia are the most notable but other electrolytes, including magnesium, may be important. Electrolyte disturbance from other causes such as parathyroid abnormalities are just as important.
• Uraemia may result in pericardial effusion.
• Long term dialysis may produce cardiomyopathy from various causes.¹⁰
• Renal damage may lead to hypertensive cardiac disease.

If there is any suspicion that the heart may be involved in systemic disease, this needs to be investigated or it may become apparent on other investigations:

• Chest x-ray may show an enlarged heart although it may not be clear if this is due to hypertrophy of the myocardium or dilation of the chambers. It may also indicate heart failure.
• Interpretation of the ECG is very important.
• Echocardiography may be valuable.
• Occasionally, other investigations including MRI scan or doppler flow studies are required.