A wide variety of systemic diseases may affect the heart by a number of different mechanisms, including increasing demands on the heart, causing arrhythmias, affecting the structure of the heart or promoting cardiovascular disease and therefore ischaemic heart disease. Common cardiac associations with systemic disease include:

• Endocrine and metabolic:
  • Diabetes mellitus: coronary artery disease, cardiomyopathy, congestive heart failure.
  • Hyperthyroidism: supraventricular tachycardia, atrial fibrillation, hypertension.
  • Hypothyroidism: bradycardia, dilated cardiomyopathy, heart failure, pericardial effusion.
  • Malignant carcinoid: tricuspid and pulmonary valve disease, right heart failure.
  • Phaeochromocytoma: hypertension, tachycardia, congestive heart failure.
  • Acromegaly: heart failure.
  • Haemochromatosis: heart failure, arrhythmias, heart block.
  • Anderson-Fabry disease: arrhythmias, coronary artery disease, heart failure.
• Nutrition:
  • Malnutrition: dilated cardiomyopathy, heart failure.
  • Thiamine deficiency: high-output heart failure, dilated cardiomyopathy.
  • Hyperhomocysteinaemia: premature atherosclerosis.
  • Obesity: cardiomyopathy, heart failure.
• Multisystem diseases:
  • Rheumatoid arthritis: pericarditis, pericardial effusion, coronary arteritis, myocarditis, valvulitis.
  • Seronegative arthropathies: aortitis, aortic and mitral insufficiency, conduction abnormalities.
  • Systemic lupus erythematosus (SLE): pericarditis, Libman-Sacks endocarditis, myocarditis, thrombosis (arterial and venous).
  • Amyloidosis: heart failure, restrictive cardiomyopathy, valvular regurgitation, pericardial effusion.
  • Sarcoidosis: heart failure, dilated or restrictive cardiomyopathy, ventricular arrhythmias, heart block.
  • Marfan's syndrome: aortic aneurysm and dissection, aortic insufficiency, mitral valve prolapse.
  • Ehlers-Danlos syndrome: aortic and coronary aneurysms, mitral valve prolapse.
• HIV infection: myocarditis, dilated cardiomyopathy, pericardial effusion.

Heart failure

Heart failure may be caused or precipitated by any condition that puts a greater demand on the heart, e.g. fever, severe anaemia, thyrotoxicosis and pregnancy.

Atherosclerosis

• 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
• There is also a strong relationship between coronary heart disease and rheumatoid arthritis.²

Hypertension

Any cause of secondary hypertension, such as renal disease (e.g. glomerulonephritis, polyarteritis nodosa, systemic sclerosis, chronic pyelonephritis, or polycystic kidneys), or endocrine disease (e.g. Cushing's syndrome, Conn's syndrome, phaeochromocytoma, acromegaly, hyperparathyroidism) may cause hypertensive heart disease, which may lead to left ventricular hypertrophy.

Lung disease

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

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

Rheumatic fever

Rheumatic fever is now very uncommon in Western Europe, although it is still seen in other parts of the world, especially Africa.

• Rheumatic fever may cause disease of the mitral valve and/or the aortic valve. This is usually mitral stenosis or aortic stenosis but mitral regurgitation or aortic regurgitation may occur alone or in combination.
• Acute rheumatic fever is also associated with myocarditis, which 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.

Other causes of valvular heart disease

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, Down's 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 (SLE), antiphospholipid antibody syndrome, the seronegative spondyloarthropathies, the systemic vasculitides, and scleroderma.³

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.

Pericardial disease

• There are separate articles Acute Pericarditis and Chronic Pericarditis and a separate Pericardial Effusion article. These are often associated with systemic disease and they 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.

Cardiomyopathy

Cardiomyopathy is discussed much more fully in the separate article Cardiomyopathies.. They may be primary or due to other disease. Many systemic diseases may cause cardiomyopathy, including:

• Sarcoidosis.
• Metabolic: diabetes, amyloidosis, Wilson's disease, haemochromatosis, glycogen storage diseases.
• Drugs and poisons:
  • Alcohol probably requires around 7 or 8 units a day for at least 5 years.⁴ However, it is probably an underdiagnosed cause and may represent 30% of dilated cardiomyopathy.⁵ Women are susceptible at a lower dose than men.⁶ High consumption of alcohol also leads to hypertension.
  • Many other substances have been implicated.⁷ Examples include cocaine, amfetamines, chemotherapy for malignancy.
• Cardiomyopathy may occur in patients on long-term dialysis.
• Endocrine disease: acromegaly, phaeochromocytoma, diabetes mellitus (maternal diabetes can also have an adverse effect on the developing fetal heart),⁸ hyperthyroidism, hypothyroidism.
• Connective tissue disorders: systemic sclerosis (may cause myocarditis or pericardial effusion), rheumatoid arthritis (can cause pericardial effusion, valvulitis and myocardial fibrosis), systemic lupus erythematosus (is associated with pericarditis, hypertension, an increased risk of coronary heart disease and Libman-Sacks endocarditis).
• Infections: acute viral infection (especially Coxsackie B), South American trypanosomiasis (Chagas' disease), hepatitis B, HIV infection.
• Nutritional: malnutrition, vitamin B1 deficiency, obesity.
• Myopathies: Duchenne's muscular dystrophy, Becker's muscular dystrophy.

Malignant disease

• Metastatic spread of malignancy to the heart is far more common than primary cardiac tumours.⁹ The most common clinical presentation is from pericardial effusion, tachyarrhythmias, atrioventricular block, and congestive heart failure.
• Tumours most likely to metastasise to the heart are malignant melanoma, leukaemia, malignant germ cell tumours 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 in the absence of metastatic spread to the heart.

Central nervous system

• 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.

Renal disease

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

• Renal impairment may impair the clearance of drugs that are potentially cardiotoxic, such as digoxin.
• Electrolyte disturbances associated with acute kidney injury or chronic kidney disease may cause cardiac abnormalities, particularly hypokalaemia, hyperkalaemia, hypercalcaemia and hypocalcaemia. Other electrolytes, including magnesium, may also be important.
• Chronic kidney disease may result in pericardial effusion.
• Long-term dialysis may cause cardiomyopathy.⁷
• Kidney disease may lead to hypertensive cardiac disease.

Assessment

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. In addition to any other investigation for the suspected underlying disease:

• Cardiovascular history and examination and clinical assessment of other systems as applicable.
• Blood tests for myocardial infarction (cardiac enzymes - particularly troponins) and/or heart failure (including brain natriuretic peptide (BNP)).
• CXR 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.
• 12-lead ECG.
• Echocardiography.
• Other investigations may be indicated, e.g. cardiac catheterisation, MRI scan or Doppler flow studies.

Document references

1. Olijhoek JK, van der Graaf Y, Banga JD, et al; The metabolic syndrome is associated with advanced vascular damage in patients with coronary heart disease, stroke, peripheral arterial disease or abdominal aortic aneurysm. Eur Heart J. 2004 Feb;25(4):342-8. [abstract]
2. Kremers HM, Gabriel SE; Rheumatoid arthritis and the heart. Curr Heart Fail Rep. 2006 Jun;3(2):57-63. [abstract]
3. Maksimowicz-McKinnon K, Mandell BF; Understanding valvular heart disease in patients with systemic autoimmune diseases. Cleve Clin J Med. 2004 Nov;71(11):881-5. [abstract]
4. Piano MR; Alcoholic cardiomyopathy: incidence, clinical characteristics, and pathophysiology. Chest. 2002 May;121(5):1638-50. [abstract]
5. Lee WK, Regan TJ; Alcoholic cardiomyopathy: is it dose-dependent? Congest Heart Fail. 2002 Nov-Dec;8(6):303-6. [abstract]
6. Fernandez-Sola J, Nicolas-Arfelis JM; Gender differences in alcoholic cardiomyopathy. J Gend Specif Med. 2002 Jan-Feb;5(1):41-7. [abstract]
7. Shik J, Parfrey PS; The clinical epidemiology of cardiovascular disease in chronic kidney disease. Curr Opin Nephrol Hypertens. 2005 Nov;14(6):550-7. [abstract]
8. Hornberger LK; Maternal diabetes and the fetal heart. Heart. 2006 Aug;92(8):1019-21. Epub 2006 May 12. [abstract]
9. Butany J, Nair V, Naseemuddin A, et al; Cardiac tumours: diagnosis and management. Lancet Oncol. 2005 Apr;6(4):219-28. [abstract]