History

Fact Explanation
Asymptomatic During very early stages patients can be asymptomatic. [2]
Chest pain Chest pain is due to myocardial ischemia. Constricting type, retrosternal chest pain may radiate to the left shoulder, neck and jaw. Some patients may present with symptoms of myocardial infarction. (constricting type retrosternal chest pain, radiating to the left arm, neck and jaw, with associated nausea, vomiting, and increased sweating. [3]
Shortness of breath Patients complain of shortness of breath on exertion initially which progresses leading to shortness of breath at rest. [3]
Reduced exercise tolerance Patient's exercise tolerance gradually diminishes due to angina. [3]
Palpitations Myocardial ischemia may induce the development of cardiac arrhythmia. In some instances patients may experience dizziness. [4]
Peripheral edema Patients develop peripheral edema secondary to heart failure. Myocardial ischemia is one of the potentially reversible causes of heart failure. [7]
Sudden cardiac death Some patients can present with sudden cardiac death due to myocardial ischemia and cardiac arrest. [4]
Erectile dysfunction Patients with atherosclerosis of the iliac vessels can develop erectile dysfunction. [3]
Intermittent claudication This is due to atherosclerotic plaques developing in the lower limb arteries. Patients develop severe calf pain with walking, which is reproducible. Calf pain relieves with rest and once the legs are kept in lower position. [3]
Symptoms of mesenteric angina Atherosclerotic plaques obliterate the mesenteric vessles leading to deminished perfusion. Mesenteric ischemia is more significant after meals, so patients complain of abdominal pain after meals. [6]
Syncope Recurrent syncopal attacks can be the presenting complain of patients with carotid artery atherosclerosis. It is due to reduced cerebral perfusion. [8]
Recurrent transient ischemic attacks (TIA) TIAs can occur in the presence of carotid artery thrombi. [5]
Presence of risk factors Unhealthy dietary habits, reduced physical activity metabolic syndrome, diabetes mellitus, hypertension, smoking, and obesity are modifiable risk factors for the development of hyperlipidemia, dyslipidemia and atherosclerosis. Positive family history of hypercholestrolemia, age and gender are non-modifiable risk factors. [1,5,9]
References
  1. GREENLAND P., ALPERT J. S., BELLER G. A., BENJAMIN E. J., BUDOFF M. J., FAYAD Z. A., FOSTER E., HLATKY M. A., HODGSON J. M., KUSHNER F. G., LAUER M. S., SHAW L. J., SMITH S. C., TAYLOR A. J., WEINTRAUB W. S., WENGER N. K., JACOBS A. K.. 2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation [online] December, 122(25):2748-2764 [viewed 07 July 2014] Available from: doi:10.1161/CIR.0b013e3182051bab
  2. KROGER K., SUCKEL A., HIRCHE H., RUDOFSKY G.. Different prevalence of asymptomatic atherosclerotic lesions in males and females. Vascular Medicine [online] 1999 May, 4(2):61-65 [viewed 07 July 2014] Available from: doi:10.1177/1358836X9900400202
  3. SCHWARTZ B. G., KLONER R. A.. Cardiovascular Implications of Erectile Dysfunction. Circulation [online] December, 123(21):e609-e611 [viewed 07 July 2014] Available from: doi:10.1161/​CIRCULATIONAHA.110.017681
  4. CORRADO D. Sudden cardiac death in young people with apparently normal heart. [online] 2001 May, 50(2):399-408 [viewed 07 July 2014] Available from: doi:10.1016/S0008-6363(01)00254-1
  5. Peripheral Arterial Disease in People With Diabetes. Diabetes Care [online] 2003 December, 26(12):3333-3341 [viewed 07 July 2014] Available from: doi:10.2337/diacare.26.12.3333
  6. HOHENWALTER EJ. Chronic Mesenteric Ischemia: Diagnosis and Treatment Semin Intervent Radiol [online] 2009 Dec, 26(4):345-351 [viewed 07 July 2014] Available from: doi:10.1055/s-0029-1242198
  7. AVERY CL, LOEHR LR, BAGGETT C, CHANG PP, KUCHARSKA-NEWTON AM, MATSUSHITA K, ROSAMOND WD, HEISS G. The population burden of heart failure attributable to modifiable risk factors: The Atherosclerosis Risk in Communities (ARIC) study J Am Coll Cardiol [online] 2012 Oct 23, 60(17):10.1016/j.jacc.2012.07.022 [viewed 07 July 2014] Available from: doi:10.1016/j.jacc.2012.07.022
  8. LANZINO G, RABINSTEIN AA, BROWN RD JR. Treatment of Carotid Artery Stenosis: Medical Therapy, Surgery, or Stenting? Mayo Clin Proc [online] 2009 Apr, 84(4):362-368 [viewed 07 July 2014] Available from: doi:10.1016/S0025-6196(11)60546-6
  9. GLAUDEMANS AW, SLART RH, BOZZAO A, BONANNO E, ARCA M, DIERCKX RA, SIGNORE A. Molecular imaging in atherosclerosis Eur J Nucl Med Mol Imaging [online] 2010 Dec, 37(12):2381-2397 [viewed 08 July 2014] Available from: doi:10.1007/s00259-010-1406-4

Examination

Fact Explanation
Peripheral stigmata of hypercholestrolemia Xantholesma, tendon xanhomata and corneal arcus are seen in hypercholestrolemia. [1]
Gallop rhythm Gallop rhythm is detectable in heart failure. Development of third heart sound is suggestive of reduced left ventricular function and fourth heart sound is an early sign. [4]
Pulse Arrhythmia can be present. Arrhythmia is induced by cardiac ischemia. [2]
Evidence of heart failure Pulmonary rales are indicative of pulmonary edema secondary to heart failure. Peripheral edema can also be detected. [5]
Respiratory rate Tachypnea is common. Can be seen in patients with heart failure and pulmonary edema. [5]
Livedo reticularis Livedo reticularis is the appearance of purplish discolored vascular pattern, which occurs secondary to multiple and small cholesterol emboli. [6]
Evidence of limb ischemia Patients with intermittent claudication can have distal limb ischemia. Dry skin, loss of hair, non-healing wounds and presence of dry gangrenes are signs of distal limb ischemia. [7]
References
  1. PIETROLEONARDO L, RUZICKA T. Skin manifestations in familial heterozygous hypercholesterolemia. Acta Dermatovenerol Alp Pannonica Adriat [online] 2009 Dec, 18(4):183-7 [viewed 07 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20043058
  2. MATSUE Y, SUZUKI M, NISHIZAKI M, HOJO R, HASHIMOTO Y, SAKURADA H. Clinical implications of an implantable cardioverter-defibrillator in patients with vasospastic angina and lethal ventricular arrhythmia. J Am Coll Cardiol [online] 2012 Sep 4, 60(10):908-13 [viewed 07 July 2014] Available from: doi:10.1016/j.jacc.2012.03.070
  3. MARTIN J, SANFILIPPO F, BRADLOW W, SABHARWAL NK. Severe vasospastic angina complicated by multiple pulseless electrical activity arrests. Lancet [online] 2013 Aug 3, 382(9890):478 [viewed 07 July 2014] Available from: doi:10.1016/S0140-6736(13)61096-X
  4. GRAYZEL J.. Gallop Rhythm of the Heart: II. Quadruple Rhythm and its Relation to Summation and Augmented Gallops. Circulation [online] 1959 December, 20(6):1053-1062 [viewed 07 July 2014] Available from: doi:10.1161/​01.CIR.20.6.1053
  5. ALDHOUS P. Britain releases green bill. Nature [online] 1990 Jan 4, 343(6253):4 [viewed 07 July 2014] Available from: doi:10.1038/343004a0
  6. A patient with atherosclerosis and livedo reticularis Postgrad Med J [online] 2001 Mar, 77(905):210 [viewed 07 July 2014] Available from: doi:10.1136/pmj.77.905.210
  7. SANTILLI JD, SANTILLI SM. Chronic critical limb ischemia: diagnosis, treatment and prognosis. Am Fam Physician [online] 1999 Apr 1, 59(7):1899-908 [viewed 07 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/10208708

Differential Diagnoses

Fact Explanation
Angina pectoris Angina can occur due to various reasons other than atherosclerosis. Coronary artery spasm, embolization, inflammation can also induce angina pectoris. [2]
Buerger disease (Thromboangiitis Obliterans) Buerger disease is a cause for nonatherosclerotic obstruction of small and medium sized vessels commonly seen in young smokers. Inflammation of the vessels in the upper and lower limbs leading to dry gangrenes is characteristic of the disease. [3]
Familial hypercholesterolemia Increased levels of total cholesterol and low density lipoprotein cholesterol is seen in familial hypercholesterolemia. Patients often have a family history of ischemic heart disease and premature death. [4]
Hypertension Hypertension is a risk factor for the development of atherosclerosis. [5]
Kawasaki disease Kawasaki disease can cause coronary artery aneurysm formation which later progress to stenosis. [6]
Pulmonary embolism Patients present with dyspnea, pleuritic chest pain and haemoptysis. [7,8]
References
  1. Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. European Heart Journal [online] 2006 March, 27(11):1341-1381 [viewed 07 July 2014] Available from: doi:10.1093/eurheartj/ehl001
  2. VLODAVER Z., NEUFELD H. N., EDWARDS J. E.. Pathology of Angina Pectoris. Circulation [online] 1972 December, 46(6):1048-1064 [viewed 07 July 2014] Available from: doi:10.1161/​01.CIR.46.6.1048
  3. VIJAYAKUMAR ABHISHEK, TIWARI RAHUL, KUMAR PRABHUSWAMY VINOD. Thromboangiitis Obliterans (Buerger’s Disease)—Current Practices. International Journal of Inflammation [online] 2013 December, 2013:1-9 [viewed 07 July 2014] Available from: doi:10.1155/2013/156905
  4. AUSTIN M. A.. Familial Hypercholesterolemia and Coronary Heart Disease: A HuGE Association Review. American Journal of Epidemiology [online] 2004 September, 160(5):421-429 [viewed 07 July 2014] Available from: doi:10.1093/aje/kwh237
  5. ALEXANDER R. W.. Hypertension and the Pathogenesis of Atherosclerosis : Oxidative Stress and the Mediation of Arterial Inflammatory Response: A New Perspective. Hypertension [online] 1995 February, 25(2):155-161 [viewed 07 July 2014] Available from: doi:10.1161/​01.HYP.25.2.155
  6. HARNDEN A., TAKAHASHI M., BURGNER D.. Kawasaki disease. BMJ [online] December, 338(may05 1):b1514-b1514 [viewed 07 July 2014] Available from: doi:10.1136/bmj.b1514
  7. MARTIN RIEDEL. Acute pulmonary embolism 1: pathophysiology, clinical presentation, and diagnosis. Heart. [online] 2001;85:229-240 [viewed 07 July 2014] Available from: doi:10.1136/heart.85.2.229.
  8. KRISTIAN THYGESEN, JOSEPH S. ALPERT HARVEY D. Universal definition of myocardial infarction. Eur Heart J. [online] 2007 28 (20): 2525-2538. [viewed 07 July 2014]. Available from: doi: 10.1093/eurheartj/ehm355

Investigations - for Diagnosis

Fact Explanation
Full blood count Chronic mesenteric angina may lead to malnutrition and hence hemoglobin levels can be low. Leukopenia, or lymphopenia can also occur. [2]
Lipid profile Total cholesterol, low density lipoprotein levels, high density lipoprotein levels and trigliceride levels are assessed in lipid profile. [3]
Fasting blood sugar Helps to diagnose previously undiagnosed diabetes. HbA1C is also helpful in diagnosing. [1]
C Reactive protein C-Reactive protein is elevated in most of the patients. [1]
Angiography Angiography is considered the gold standard in diagnosing atherosclerotic vascular stenosis. [2]
Ultrasound scan Ultrasound scan is helpful in assessing the vessel wall thickness and the degree of luminal stenosis. Duplex ultrasound is used to diagnose mesenteric vessel atherosclerosis. [2,5]
ECG [1] Presence of ischemic changes (ST segment elevation or depression, T inversion) is helpful in diagnosing acute coronary syndrome.
Cardiac biomarkers Elevated cardiac biomarkers in combination with ECG helps to diagnose an acute coronary syndrome. [4]
Echocardiogram [1] Echocardiogram is useful in diagnosing acute coronary syndrome. Ventricular wall motion abnormalities can be detected.
Nuclear imaging studies This test is helpful in assessing the degree of coronary artery stenosis and the biological activity of the atherosclerotic plaque. Nuclear stress test can detect inducible myocardial ischemia. [5]
MRI MRI scan is sensitive, non-invasive and safe method of investigating for the presence of atherosclerosis when compared with CT scan. Cardiac MRI can detect the presence of coronary atherosclerosis and the site of it. [2,5]
CT scan Multidetector computed tomography is more sensitive in detecting coronary artery stenosis, but it uses a higher radiation dose. Electron beam CT is a novel and non-invasive method of evaluating the degree of coronary artery stenosis. CT angiography helps to identify atherosclerotic lesions with high risk of rupture. The site of the atherosclerosis can also be detected. [2,5]
B-type natriuretic peptide (BNP) BNP is elevated in heart failure. It should only be done in patients with symptoms of heart failure. [1]
Optical coherence tomography (OCT) OCT can detect intravascular plaques. OCT has higher resolution of images than the intravascular scans. [5]
Intravascular ultrasound scan [1] Intravascular ultrasound scan can detect intravascular plaques. [5]
Doppler scan Doppler scan is helpful in evaluating claudication. [5]
Urinary microalbumin Assessment of urinary microalbumin is indicated in all patients with diabetes and hypertension in the assessment of cardiovascular risk profile. [1]
References
  1. GREENLAND P., ALPERT J. S., BELLER G. A., BENJAMIN E. J., BUDOFF M. J., FAYAD Z. A., FOSTER E., HLATKY M. A., HODGSON J. M., KUSHNER F. G., LAUER M. S., SHAW L. J., SMITH S. C., TAYLOR A. J., WEINTRAUB W. S., WENGER N. K., JACOBS A. K.. 2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation [online] December, 122(25):2748-2764 [viewed 07 July 2014] Available from: doi:10.1161/CIR.0b013e3182051bab
  2. HOHENWALTER EJ. Chronic Mesenteric Ischemia: Diagnosis and Treatment Semin Intervent Radiol [online] 2009 Dec, 26(4):345-351 [viewed 07 July 2014] Available from: doi:10.1055/s-0029-1242198
  3. PENALVA RA, HUOYA MDE O, CORREIA LC, FEITOSA GS, LADEIA AM. Lipid profile and intensity of atherosclerosis disease in acute coronary syndrome. Arq Bras Cardiol [online] 2008 Jan, 90(1):24-30 [viewed 08 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/18317637
  4. CALISKAN Y, OZKOK A, AKAGUN T, ALPAY N, GUZ G, POLAT N, TUFAN F, ECDER T, BOZFAKIOGLU S. Cardiac biomarkers and noninvasive predictors of atherosclerosis in chronic peritoneal dialysis patients. Kidney Blood Press Res [online] 2012, 35(5):340-8 [viewed 08 July 2014] Available from: doi:10.1159/000332084
  5. GLAUDEMANS AW, SLART RH, BOZZAO A, BONANNO E, ARCA M, DIERCKX RA, SIGNORE A. Molecular imaging in atherosclerosis Eur J Nucl Med Mol Imaging [online] 2010 Dec, 37(12):2381-2397 [viewed 08 July 2014] Available from: doi:10.1007/s00259-010-1406-4

Investigations - Fitness for Management

Fact Explanation
Full blood count Detect the presence of anemia which can occur secondary to chronic malnutrition. Anemia can worsen the symptoms as well. [1]
Serum electrolytes Assesses the baseline renal function. Chronic malnutrition can also lead to electrolyte imbalances. [1]
Serum protein Serum protein especially albumin is decreased in chronic malnutrition. Hypoproteinemia delays the wound healing. [1]
References
  1. HOHENWALTER EJ. Chronic Mesenteric Ischemia: Diagnosis and Treatment Semin Intervent Radiol [online] 2009 Dec, 26(4):345-351 [viewed 07 July 2014] Available from: doi:10.1055/s-0029-1242198

Investigations - Followup

Fact Explanation
Lipid profile Lipid profile should be done in all patients to monitor and optimize the lipid lowering therapy.
Exercise ECG Exercise ECG should be done to assess the patient's functionality. [1]
Duplex scan After therapeutic revascularization pocedures, Duplex scan is useful in evaluating the patency of the vessles and the success of revascularization. [2]
References
  1. GREENLAND P., ALPERT J. S., BELLER G. A., BENJAMIN E. J., BUDOFF M. J., FAYAD Z. A., FOSTER E., HLATKY M. A., HODGSON J. M., KUSHNER F. G., LAUER M. S., SHAW L. J., SMITH S. C., TAYLOR A. J., WEINTRAUB W. S., WENGER N. K., JACOBS A. K.. 2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation [online] December, 122(25):2748-2764 [viewed 07 July 2014] Available from: doi:10.1161/CIR.0b013e3182051bab
  2. SAUCY F., DISCHL B., DELACHAUX A., FEIHL F., LIAUDET L., WAEBER B., CORPATAUX J.-M.. Foot Skin Blood Flow Following Infrainguinal Revascularization for Critical Lower Limb Ischemia. European Journal of Vascular and Endovascular Surgery [online] 2006 April, 31(4):401-406 [viewed 08 July 2014] Available from: doi:10.1016/j.ejvs.2005.10.026

Investigations - Screening/Staging

Fact Explanation
Myocardial fractional flow reserve This is used to assess the functional severity of the coronary artery stenosis. [2]
Doppler scan Doppler scan can assess the severity of vessle stenosis, especially useful in evaluating intermittent claudication. Measurement of ankle-brachial pressure index is helpful in the assessment of severity of claudication. [1]
References
  1. GREENLAND P., ALPERT J. S., BELLER G. A., BENJAMIN E. J., BUDOFF M. J., FAYAD Z. A., FOSTER E., HLATKY M. A., HODGSON J. M., KUSHNER F. G., LAUER M. S., SHAW L. J., SMITH S. C., TAYLOR A. J., WEINTRAUB W. S., WENGER N. K., JACOBS A. K.. 2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation [online] December, 122(25):2748-2764 [viewed 07 July 2014] Available from: doi:10.1161/CIR.0b013e3182051bab
  2. DE BRUYNE B., BARTUNEK J., SYS S. U., HEYNDRICKX G. R.. Relation Between Myocardial Fractional Flow Reserve Calculated From Coronary Pressure Measurements and Exercise-Induced Myocardial Ischemia. Circulation [online] 1995 July, 92(1):39-46 [viewed 08 July 2014] Available from: doi:10.1161/​01.CIR.92.1.39

Management - General Measures

Fact Explanation
Health education Patients should be advised about the preventive measures of atherosclerosis. Healthy diet and regular exercise (thirty minutes a day for at least five days a week) are helpful in primordial prevention. Patients with recognized risk factors should be advised to achieve a better control of comorbidities. Obese patients should achieve the normal BMI with adequate weight reduction. A diet with low saturated fat (less than 7% of total energy intake), and more vegetables and fruits is recommended. Framingham risk score should be used to calculate the cardiovascular risk. [2]
Management of diabetes mellitus Patients with diabetes mellitus have increased risk of complications of atherosclerosis. Strict blood sugar control is necessary in delaying those complications. [3]
Management of hypertension Prolonged hypertension can destabilize the atherosclerotic plaques and precipitate acute coronary events. [4]
Thromboprophylaxis Antiplatelet drugs (aspirin, clopidogrel) are indicated to minimize the risk of acute coronary syndrome. Aspirin is indicated for the treatment of patients with intermittent claudication as well. Long term anticoagulation is indicated for patients who are not fit enough to undergo surgery. Clopidogrel should be continued in patients who has underwent stent implantation. [1]
References
  1. HOHENWALTER EJ. Chronic Mesenteric Ischemia: Diagnosis and Treatment Semin Intervent Radiol [online] 2009 Dec, 26(4):345-351 [viewed 07 July 2014] Available from: doi:10.1055/s-0029-1242198
  2. THOMPSON P. D.. Exercise and Physical Activity in the Prevention and Treatment of Atherosclerotic Cardiovascular Disease: A Statement From the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity). Circulation [online] 2003 June, 107(24):3109-3116 [viewed 08 July 2014] Available from: doi:10.1161/​01.CIR.0000075572.40158.77
  3. BECKMAN JOSHUA A., CREAGER MARK A., LIBBY PETER. Diabetes and Atherosclerosis. JAMA [online] 2002 May [viewed 08 July 2014] Available from: doi:10.1001/jama.287.19.2570
  4. OLAFIRANYE OLADIPUPO, ZIZI FERDINAND, BRIMAH PERRY, JEAN-LOUIS GIRARDIN, MAKARYUS AMGAD N., MCFARLANE SAMY, OGEDEGBE GBENGA. Management of Hypertension among Patients with Coronary Heart Disease. International Journal of Hypertension [online] 2011 December, 2011:1-6 [viewed 08 July 2014] Available from: doi:10.4061/2011/653903

Management - Specific Treatments

Fact Explanation
Lipid lowering therapy Lipid lowering therapy is indicated in all patients to lower the serum lipid levels. Statins are widely used. [3,4]
Treatment of angina Beta blockers, calcium channel blockers and nitrates are indicated for the symptomatic management of angina. Surgical management options include percutaneous coronary intervention (PCI), and coronary artery bypass graft. Transmyocardial laser revascularization is a newer treatment modality. [5]
Lower limb amputation If irreversible limb ischemia has occurred amputation is the only available treatment option. [1]
Management of mesenteric atherosclerosis Open surgical treatment (transaortic endarterectomy, direct reimplantation on the aorta, and antegrade or retrograde bypass grafting) was considered the most effective treatment modality in the past. With the recent development of therapeutic angiographic procedures, angioplasty and stenting of the mesenteric arteries is considered a less invasive method of treatment. [2]
References
  1. Peripheral Arterial Disease in People With Diabetes. Diabetes Care [online] 2003 December, 26(12):3333-3341 [viewed 07 July 2014] Available from: doi:10.2337/diacare.26.12.3333
  2. HOHENWALTER EJ. Chronic Mesenteric Ischemia: Diagnosis and Treatment Semin Intervent Radiol [online] 2009 Dec, 26(4):345-351 [viewed 07 July 2014] Available from: doi:10.1055/s-0029-1242198
  3. GOTTO A. M.. Lipid Lowering, Regression, and Coronary Events : A Review of the Interdisciplinary Council on Lipids and Cardiovascular Risk Intervention, Seventh Council Meeting. Circulation [online] 1995 August, 92(3):646-656 [viewed 08 July 2014] Available from: doi:10.1161/​01.CIR.92.3.646
  4. GRUNDY S. M., BALADY G. J., CRIQUI M. H., FLETCHER G., GREENLAND P., HIRATZKA L. F., HOUSTON-MILLER N., KRIS-ETHERTON P., KRUMHOLZ H. M., LAROSA J., OCKENE I. S., PEARSON T. A., REED J., SMITH S. C., WASHINGTON R.. When to Start Cholesterol-Lowering Therapy in Patients With Coronary Heart Disease : A Statement for Healthcare Professionals From the American Heart Association Task Force on Risk Reduction. Circulation [online] 1997 March, 95(6):1683-1685 [viewed 08 July 2014] Available from: doi:10.1161/​01.CIR.95.6.1683
  5. POOLE-WILSON P. A.. Treatment of angina: a commentary on new therapeutic approaches. European Heart Journal Supplements [online] 2006 February, 8(Suppl A):A20-A25 [viewed 08 July 2014] Available from: doi:10.1093/eurheartj/sui093