Category Archives: Cardiovascular disease

Thromboangiitis obliterans

(Buerger’s disease)

This disease, involving the small vessels of the lower limbs, occurs in young men who smoke. It is thought by some workers to be indistinguishable from atheromatous disease. However, pathologically there is inflammation of the vessels that may indicate a separate disease activity. Clinically it presents with peripheral ischaemia and patients must stop smoking.

Takayasu’s syndrome

This is rare, except in Japan. It is known as ‘pulseless disease’ or the aortic arch syndrome. It is of unknown aetiology and occurs in young females. There is a vasculitis involving the aortic arch as well as other major arteries. There is also a systemic illness, with pain and tenderness over the affected arteries. Absent peripheral pulses and hypertension are usually found. Corticosteroids help the constitutional symptoms. Heart failure and cerebrovascular accidents eventually occur, but most patients survive for at least 5 years. Kawasaki disease (mucocutaneous lymph node syndrome)
This is an uncommon acute febrile illness of early childhood. There is a generalized vasculitis with involvement of the coronary arteries and lymphadenopathy.

Cardiovascular syphilis

This gives rise to:
• Uncomplicated aortitis
• Aortic aneurysms, usually in the ascending part
• Aortic valvulitis with regurgitation
• Stenosis of the coronary ostia
The diagnosis is confirmed by serology. Treatment is with penicillin. Aneurysms and valvular disease are treated as necessary by the usual methods.

Two-dimensional transoesophageal

Two-dimensional transoesophageal

Connective tissue disorders

These cause vasculitis and can’ give rise to peripheral vascular disease.

Raynaud’s disease and phenomenon

Raynaud’s phenomenon consists of spasm of the arteries supplying the fingers or toes and is usually precipitated by  cold and relieved by heat. When Raynaud’s phenomenon occurs without any underlying disorder, it is then known as Raynaud’s disease. This is a common disease affecting 5% of the population and occurring predominantly in  young women. The disorder is usually bilateral and  fingers are affected more commonly than toes. There is an  initial pallor of the skin resulting from vasoconstricion and this is followed by cyanosis due to sluggish blood  flow. Redness finally occurs owing to hyperaemenia. The  duration of the attacks can be variable and can sometimes last for hours. Numbness and burning of the fingers usually ally occurs and pain can be severe, particularlv in the  rewarming phase.

Between the attacks the pulses and the digits appear  normal, but trophic changes with small areas of gangrene can occur in severe and persistent cases.


Primary Raynaud’s disease must be differentiated from secondary causes of Raynaud’s phenomenon,which are  chiefly disorders of connective tissue, particularly systemic sclerosis. It can also occur in cryoglobulinaemia and as a side-effect of drug treatment, especiallv with B blocking agents.


No treatment is usually required for the attacks but any  underlying disease must be looked for.The hand and feet should be kept warm, and smoking should be avoided. f3-Blockers should be stopped. Nifedipine 10 mg three times daily may be helpful.


Varicose veins

Varicose veins are a common problem, sometimes giving rise to pain. They are treated by injection or surgery. Venous thrombosis Thrombosis can occur in any vein, but the veins of the leg and the pelvis are the commonest sites.

Superficial thrombophlebitis

This commonly involves the saphenous veins and is often associated with varicosities. Occasionally the axillary vein is involved, usually as a result of trauma. There is local superficial inflammation of the vein wall, with secondary thrombosis.
The clinical picture is of a painful, tender, cord-like structure with associated redness and swelling. The condition usually responds to symptomatic treatment with rest, elevation of the limb and analgesics (e.g. non-steroidal anti-inflammatory drugs). Anticoagulants are not necessary, as embolism does not occur from superficial thrombophlebitis.

Deep-vein thrombosis

A thrombus forms in the vein, and any inflammation of the vein wall is secondary to this. Thrombosis commonly occurs after periods of immobilization, but it can occur in normal individuals for no obvious reasons. The precipitating factors are discussed.
Deep-vein thrombosis occurs in 50% of patients after prostatectomy or following a cerebral vascular accident. In addition, one-third of patients with a myocardial infarct have a deep-vein thrombosis.
Thrombosis can occur in any vein of the leg, but is particularly found in veins of the calf. It is often undetected; autopsy figures give an incidence of over 60% in hospitalized patients.

CLINICAL FEATURES. The major presenting features are:
ASYMPTOMATIC, presenting with clinical features of pulmonary embolism.
PAIN IN THE CALF, often presenting with swelling, redness and engorged superficial veins. The affected calf is often warmer and there may be ankle oedema. Homan’s sign (pain in the calf on dorsiflexion of the foot) is often present, but is not diagnostic and occurs with all lesions of the calf.
Thrombosis in the iliofemoral region can present with  severe pain, but there are often few physical. signs apart from occasional swelling of the thigh and/or ankle oedema.

Complete occlusion, particularly of a large vein, can lead to a cyanotic discoloration of the limb and severe  zedema, which can very rarely lead to venous gangrene. Pulmonary embolism can occur with any deep-vein thrombosis but is more frequent from an iliofemoral thrombosis and is rare with thrombosis confined to veins below the knee. Spread of thrombosis can occur proximally without clinical evidence, so the extent of the thrombosis must be carefully assessed.
INVESTIGATION. Clinical diagnosis is unreliable and confirmation of an iliofemoral thrombosis can usually be made with ultrasound or Doppler ultrasound. Belowknee thromboses can only reliably be detected by venography but whether this is necessary is questionable (see Treatment). A venogram is performed by injecting a vein in the foot with contrast which will detect virtually all thrombi that are present.
TREATMENT. The main aim of therapy is to prevent pulmonary embolism and all patients with thrombi above the knee must be anticoagulated. Anticoagulation of below-knee thrombi is controversial. Bed rest is advised until the patient is fully anticoagulated. The patient should then be mobilized, with an elastic stocking giving graduated pressure over the leg. Heparin is given normally for 48 hours but how long warfarin should be given is debatable-3 months is the usual recommended period but 4 weeks is long enough if a definite risk factor (e.g. bed rest) has been present.
The INR should be at 2-3.0. Anticoagulants do not affect the thrombus that is already present. Thrombolytic therapy is occasionally used for patients with a large iliofemoral thrombosis.
PROGNOSIS. Destruction of the deep-vein valves produces a clinically painful, swollen limb that is made worse by standing and is accompanied by oedema and sometimes venous eczema. It occurs in approximately half of the patients with a clinically symptomatic deep-vein thrombosis, and it means that elastic support stockings are then required for life.
PREVENTION. Subcutaneous low-dose heparin should be given to patients with cardiac failure, a myocardial infarct or surgery to the leg or pelvis. Early ambulation is indicated as most thromboses occur within the first 72 hours following surgery. Leg exercises should be encouraged and patients should not sit in a chair with their legs immobilized on a stool. An elastic support stocking should be given to patients at high risk, e.g those with a history of thrombosis or with obesity.

Further Reading

Anderson HV & Willenson JT Thrombolysis in acute myocardial infarction. New England Journal of Medicine 329, 703-709.

Braunwald E (1987) Heart Disease, 3rd edn. Philadelphia: WB Saunders. Fuster Vet al. (1992) The pathogenesis of coronary artery disease and the acute coronary syndromes. New England Journal of Medicine 326, 242-250 and 310- 318.
Hampton JR (1986) The ECG Made Easy, 3rd edn. Edinburgh: Churchill Livingstone.
Hurst JW (1990) The Heart, Arteries and Veins, 7th edn. New York: McGraw-Hill. Julian DG, Camm AJ, Fox KS, Hall RJC & Poole-Wilson PA (1995) Diseases of the Heart, 2nd edn, in press. London: Bailliere Tindall.

Kelly DP & Strauss AW (1994) Inherited cardiomyopathies. New England Journal of Medicine 330, 913-919.
Landau C, Lange R & Hillis LD (1994) Percutaneous transluminal coronary angioplasty. New England Journal of Medicine 330, 981-993.
Severs P et al. (1993) Guidelines for the treatment of hypertension. British Medical Journal 306, 983-987. Sokolow M & McIlroy MB (1986) Clinical Cardiology, 4th edn. New York: Lange.

Peripheral vascular disease


This can be due to a number of pathological processes.


This is the term applied to generalized, age-related arterialchanges, which are exaggerated in hypertension. In arteries down to 1 mm in diameter these changes initially take the form of compensatory muscular hypertrophy of the media, which is followed by fibrosis and dilatation of the lumen. In hypertensive vessels of this size, atheroma is often superadded.
Smaller arteries show different changes that are usually most marked in the viscera, especially in the kidneys. Here, though there is medial hypertrophy, the predominant change is intimal thickening by concentric layers of connective tissue, with luminal narrowing. Arterioles undergo hyaline thickening of their walls and luminal narrowing. The narrowing of small vessels in the kidney owing to hypertension causes renal ischaemia, which further promotes hypertension.

In malignant hypertension, arterioles also show fibrinoid necrosis of their walls.

Monckeberg’s sclerosis

This is a degenerative disease of unknown cause, characterized by dystrophic calcification of the media. It is especially common in the major lower limb arteries of the elderly, and there is an increased incidence of this degeneration in diabetics.
Cystic medial necrosis or degeneration This describes mucoid degeneration of the collagen and elastic tissue of the media, often with cystic changes. It occurs mainly in elderly hypertensives. Dissecting aneurysms of the thoracic aorta are often due to this process. Cystic medial degeneration also occurs in inherited defects of collagen tissue formation (e.g. Marfan’s syndrome, Ehlers-Danlos syndrome), again resulting in dissecting aneurysms .


The pathogenesis of this condition is described. The different vessels which may be involved are shown. Atheroma seldom involves arteries of less than 2 mm in diameter. Most arterial disease is due to atheromatous degeneration.

Chronic ischaemia of the legs

This is due to atheromatous disease involving the aorta, iliac and/or any other peripheral vessels. It consequently occurs over the age of 50 years, chiefly in men who are smokers.


• Ischaemic, cramp-like pain, usually in the calves during exercise and relieved by rest (intermittent claudication)
• Rest pain
• Non-healing leg ulcers or gangrene
Both limbs are often affected, but usually one is more severely affected than the other.


• A cold limb with dry skin and lack of hair
• Absent pulses to diseased areas
• Ulceration or gangrene


X- RAY S may show calcification of the arteries of the leg. DOPPLER ULTRASOUND defines the severity of the lesion.

Common sites of clinically significant atherosclerosis in order of frequency.

Common sites of clinically significant
atherosclerosis in order of frequency.

AORTOGRAPHY by direct injection of contrast medium into the aorta is used. Angiography is also performed via a percutaneous catheter inserted into the brachial artery and digital vascular imaging with an intravenous injection has been used. These investigations show narrowing and stenosis of the arteries.



RISK FACTORS should be reduced (e.g. smoking should be stopped, diabetes and hypertension should be treated, and weight should be reduced). THE LIMBS should be kept warm but local heat should not be applied. FEET. Care should be taken to avoid infection and trauma of the feet. Elderly patients often need regular visits to a chiropodist.
REGULAR EXERCISE should be taken to encourage the development of anastomotic vessels. LOW-DOSE ASPIRIN should be given. VASODILATORS should not be used.
ANTICOAGULANTS are of no benefit.


TIMING. Surgery should not be considered for 3 months after symptoms have developed, to allow time for collaterals to develop. In 75% of patients the disease remains static.
AORTO-ILIAC BYPASS grafts give good results, but reconstructive surgery for blockages below the inguinal ligament is less successful.
BALLOON DILATATION via a catheter inserted into the artery is useful for local iliac or femoral stenoses. AMPUTATION is necessary for severely ischaemic limbs, usually those with gangrene. Rehabilitation may take months in the elderly and is often unsuccessful. Many of the patients have generalized atheromatous conditions, so that the overall prognosis often dictates the outcome of localized disease; many die from a myocardial infarction.

Acute ischaemia of the legs

Like chronic ischaemia of the legs, this is mainly due to atheromatous disease with thrombosis, but it can also occur owing to embolism from the heart (e.g. in atrial fibrillation) or from an atheromatous central vessel. The clinical picture is of an acutely painful, pale, paralysed, pulseless limb.
Treatment is surgical, with removal of the clot. If gangrene develops, amputation is necessary.

Aortic aneurysms

Abdominal aneurysms

The commonest aortic aneurysms are abdominal. These are usually due to atheroma. Asymptomatic aneurysms may be found as a pulsatile mass on examination or as calcification on an X-ray. A CT scan or ultrasound of the abdomen will demonstrate the size of the aneurysm, the thickness of the aortic wall and whether any leak has occurred. An expanding aneurysm may cause epigastric or back pain. Rupture presents with epigastric pain radiating through to the back. A pulsatile mass is felt and the patient is shocked. Treatment of symptomatic aneurysms is surgical. A ruptured aneurysm requires emergency surgery, but even then the mortality is high. Large, asymptomatic aneurysms should also be treated surgically (except in the very old) because those larger than 5 em in diameter have a high risk of rupture. Follow- up with ultrasound is required with small aneurysms and surgery offered when aneurysm reaches 5 cm.

Thoracic aneurysms

Most thoracic aneurysms in the past were due to syphilis, but now many are due to atheromatous disease. The aneurysms may affect all parts of the thoracic aorta-the ascending aorta, the arch and the descending aorta. Most are asymptomatic, but when large they can give rise to chest pain or to evidence of pressure on other organs, such as the superior vena cava or the oesophagus. They can rupture.

Dissecting aortic aneurysms

In the majority of cases, the dissection starts in the ascending aorta. Pain, which is severe and central, often radiating to the back, is the major symptom. The pain radiates down the arms and into the neck and can be difficult to distinguish from myocardial infarction. On examination, the patient is usually shocked and there may be neurological signs owing to the involvement of the spinal vessels. The peripheral pulses may be absent, but this is not invariable. The diagnosis is suggested by the presence of back pain with no ECG or enzyme changes of myocardial infarction. The chest X-ray may show a wide mediastinum and CT scanning and ultrasonography with transoesophageal echocardiography if available are diagnostic.
Aortography is now rarely necessary to confirm the diagnosis.
Half of the patients are hypertensive and this should be controlled immediately. Emergency surgery is necessary for many dissections.
There is an increased risk of dissection in pregnancy. Patients with Marfan’s syndrome are at particular risk of dissection originating at the root of the aorta. Risk can be assessed by measuring the dimension of the aortic root using serial echocardiography. Elective repair of the aneurysmal aortic root is indicated if the dimensions increase rapidly.

The heart in pregnancy

In pregnancy the cardiac output and blood volume increase from the second month up to the thirtieth week to 30-50% above the normal levels. This, along with the increased metabolic work, produces the physical signs of warm extremities, a tachycardia with a large-volume pulse and a slight rise in venous pressure. The apex beat is  displaced, owing partly to cardiomegaly and partly to a raised diaphragm. The increased blood flow produces a pulmonary systolic murmur and a third heart sound. The diastolic blood pressure is lower owing to vasodilatation. The added burden of pregnancy on the cardiovascular system can make underlying, otherwise latent, disease clinically apparent. Ten per cent of maternal deaths in England and Wales are due to heart disease. This is usually rheumatic or congenital in origin, but any heart disease can be seen in pregnancy. Moderate to severe mitral stenosis can cause breathlessness early in pregnancy and may lead to pulmonary oedema later in pregnancy. Pregnancy should be avoided in severe mitral stenosis or delayed until after valvotomy. Termination may be necessary in a severe case occurring before the sixteenth week. Most cases of congenital heart disease have been corrected by the time women reach the reproductive age. However, patients with small and uncomplicated septal defects usually tolerate pregnancy well. Patients with prosthetic valves are usually on anticoagulant therapy. This may require a change to heparin because warfarin can cause fetal abnormalities. Patients with pulmonary hypertension of any aetiology have an extremely high mortality (up to 50%) either during or immediately after delivery, and termination should be considered. Post parium, or late in pregnancy, a cardiomyopathy of uncertain aetiology is sometimes seen. There is also a rise in thromboembolic complications of cardiac disease owing to the hypercoagulability that exists post partum. Sepsis is a risk during delivery, and patients with heart disease may be at risk of developing infective endocarditis.

Heart disease in the elderly’

As the average age of the population increases, cardiac disease predominates. The elderly population are vulnerable to most forms of heart disease, especially coronary artery disease, hypertension, arrhythmias and degenerative pathologies.
Diagnosis of mild forms of heart disease may be difficult in the elderly. The wear and tear of age results in some features that would be regarded as abnormal in the young. For example, a fourth heart sound and a systolic aortic ejection murmur are common findings on examining normal elderly adults. The ECG often shows slight PR interval prolongation (to 0.22 s), left axis deviation and T wave flattening. On the chest X-ray there may be some aortic, valvular or coronary arterial calcification, but the cardiac silhouette is usually normal. The echo cardiogram  may show mild myocardial hypertrophy and buckling of the ventricular septum. It is particularly difficult to diagnose and define hypertension in the elderly. Cuff blood pressure usually overestimates intravascular pressure if the old arterial wall is stiff (pseudohypertension). Normally blood pressure steadily increases with age, at least up to the age of 70 years, and blood pressure is particularly labile in the elderly. In the very old (>80 years) there is only a weak association between ‘hypertension’ and diseases such as stroke, myocardial infarction and heart failure.
Cardiac disease may present in unexpected ways in an old person. It is not unusual for significant bradycardia to present as a fractured hip because the fall that caused the fracture resulted from transient asystole. Left heart failure may present as an acute confusional state due to poor cerebral perfusion, rather than with the classical symptom of breathlessness. Myocardial infarction may not cause any chest pain (‘silent’ myocardial infarction) but may present as weakness or abdominal pain.
The principles of treatment of heart disease in old people are usually no different from those governing treatment  in the young. However, it is important to remember that drug pharmacokinetics are changed in the elderly: absorption is reduced, renal and hepatic clearance are delayed, body fat increases and lean body mass decreases. Old people may forget to take their medications or be confused about the correct dose. Some therapies seem inappropriate or futile in the elderly. For example, it is probably unnecessary to inflict a spartan life-style or rigorous uncomfortable drug therapy on an old person in an attempt to modify the risk of developing coronary disease. However, there are treatments that have emerged in recent years that are extremely useful for old people, for example, hypertension should be treated (see p. 621). Coronary angioplasty, and perhaps mitral/aortic valvuloplasty, can be undertaken in patients too frail to consider for surgery. Cardiac surgery does carry a much greater (approximately two to five times) risk in the elderly but, as with younger patients, the absolute risk is dependent upon the state of the myocardium, the extent of cardiac disease and the condition of other organ systems. Age is no bar to effective treatment of heart disease.
There are a few cardiac conditions that are largely confined to the elderly.
AORTIC SCLEROSIS results from fibrosis and calcification on the aortic side of an otherwise normal tricuspid aortic valve. This may result in an obstruction to left ventricular outflow but it is often trivial. Aortic valve replacement may be necessary if the obstruction
IS severe.
MITRAL ANNULUS CALCIFICATION occurs predominantly in old women. It is diagnosed from the chest Xray and it is not usually responsible for any symptoms.
ENDOCARDITIS. A non-infective form of endocarditis may occur in the elderly. It is a hypercoagulable state that presents with cachexia, thrombosis and embolization. Anticoagulation may be needed.
LEV’S DISEASE. Disruption of His-Purkinje conduction by fibrosis and calcification is most common in the old when it is known as Lev’s disease. It presents with Stokes-Adams attacks and must be treated by pacemaker insertion.
ATRIAL FIBRILLATION is much more common in the old but it is often well tolerated and may not need any active treatment for control of heart rate. Anticoagulation should be considered.


In the young, the secondary causes of hypertension should be excluded before treatment is commenced. When the blood pressure is only mildly or moderately elevated, it may be difficult to persuade an asymptomatic patient that treatment is necessary. However, there are definite advantages from treating diastolic blood pressures in excess of 100 mmHg. If the diastolic blood pressure is between 90 and 100 mmHg it should be carefully reassessed on several occasions with the patient in a comfortable, relaxed position. If it is truly elevated (above 90 mmHg) it should be actively treated, especially in young men, and particularly so if there is any vidence of retinal, cardiac or renal end-organ damage. There is no evidence to support treating mild to moderate blood pressure elevation in the very old (>80 years). However, patients between 65 and 80 years with a diastolic pressure above 90 mmHg or a systolic blood pressure above 160 mmHg or both do benefit from treatment. The Framingham studies have shown that the systolic blood pressure in this group is as important as the diastolic blood pressure and is the best guide to the risk of peripheral arterial disease. Thus, a man with a systolic pressure of 170 mmHg has twice the risk of dying compared with a man with a systolic pressure of 120 mmHg. Only in the elderly has it been demonstrated that isolated systolic hypertension is associated with an increased risk of cardiovascular events. Nevertheless it is recommended that patients of all ages with a persistent systolic pressure above 160 mmHg should be treated. The thresholds for drug treatment of hypertension which have been recommended by the British Hypertension Society are illustrated.

General measures

A review of the patient’s life-style and diet may suggest modifications that could lead to some reduction of blood pressure, such as:
WEIGHT REDUCTION. Obese patients should lose weight. This leads to a true fall in blood pressure as well as to a reduction of artefactually increased cuff measurements.
This also leads to a small reduction in blood pressure of around 5-10 mmHg.
SALT RESTRICTION. This is generally of little effect except in some individuals. Usually, the patient is advised not to add salt at the table.
REGULAR EXERCISE, MEDITATION AND BIOFEEDBACK. These are all techniques that have been claimed to lead to blood pressure reduction. An attempt should be made to reduce stress and anxiety.
Young people should jog for 30 min three times per week and elderly patients should walk longer distances than usual.
Patients should also be told to stop smoking to reduce their overall coronary risk. It is doubtful whether cessation of smoking reduces the blood pressure except in malignant hypertension. Hyperlipidaemia should also be corrected to reduce the risk of atheroma.

Drug treatment

A large number of drugs are used to treat hypertension. This reflects the difficulty in finding a single drug that effectively lowers blood pressure without producing side-effects that may be more troublesome or more dangerous than the hypertension itself. Compliance is a problem as the side-effects of drug therapy are frequent and the immediate benefits of treatment are not obvious to the patient.

Available drugs

DIURETICS. Loop diuretics (e.g. frusemide 40 mg daily or bumetanide 1-2 mg daily) and thiazide diuretics (e.g. bendrofluazide 5 mg daily or cyclopenthiazide 0.5 mg daily) are equally effective at lowering the blood pressure. Thiazides are usually preferred because the duration of action is longer, the diuresis is not so severe, and they cost less. Loop diuretics are restricted to those with cardiac or renal impairment for whom an additional diuretic effect is required.
Although diuretics may lower blood pressure transiently by sodium and water excretion, they also act by directly dilating arterioles. Oral potassium supplements are often not required. Occasionally, hypokalaemia occurs and this is most effectively treated with a potassiumsparing diuretic.

Thresholds for treatment of diastolic

Thresholds for treatment of diastolic

Advantages and disadvantages of hypotensive drugs with respect to associated conditions (modified from British Hypertension Society).

Advantages and disadvantages of hypotensive drugs with respect to associated conditions (modified from British Hypertension Society).

Potassium-sparing diuretics (e.g. triamterene 150- 250 mg daily, spironolactone 50-200 mg and amiloride 5-10 mg daily) are not effective hypotensive agents, with the exception of spironolactone in primary or secondary aldosteronism. These diuretics are combined with others to treat hypokalaemia, which very occasionally occurs in hypertensive patients on diuretics. Thiazide diuretics may cause hyperuricaemia and may precipitate gout. They may worsen glucose intolerance. Thiazide diuretics increase the serum renin level. Unlike other hypotensives, their effect is not postural. f3-ADRENERGIC ANTAGONISTS. The mechanism by which f3-blockers reduce hypertension is unclear. Although they reduce the force of cardiac contraction and renin production, they probably act predominantly via the central nervous system. f3-Blockers also reduce anxiety. Propranolol 80 mg twice daily, ateno- 101 50-100 mg daily and oxprenolol 80 mg twice daily have been most widely used for the treatment of blood pressure, but there is a wide range of f3-blockers with  different properties:
CARDIOSELECTIVITY implies a greater effect on 131- receptors (cardiac receptors) than on f32-receptors. Such a selective effect is preferred when bronchospasm, intermittent claudication or diabetes is present. Metoprolol, atenolol and acebutolol are cardioselective 13- blockers.
INTRINSIC SYMPATHOMIMETIC ACTIVITY is necessary if bradycardia complicates therapy with 13- blockade. Pindolol has the largest degree of ISA. POOR LIPID SOLUBILITY (e.g. sotalol) is an advantage  if central nervous system side-effects are prominent. The complications of f3-blockade include aggravation of ventricular failure, bradycardia, cold extremities, aching muscles, fatigue, weakness, bad dreams and hallucinations. Non-selective f3-blockade may lead to elevation of serum potassium and may mask or prolong the effects  of hypoglycaemia. f3-Blockers can, however, usefully be used in patients with both hypertension and angina.
VASODILATORS. Dilatation of the peripheral arterioles leads to a fall in blood pressure. There are many mechanisms by which vasodilatation can be achieved.
CALCIUM ANTAGONISTS such as nifedipine (20 mg twice daily), diltiazem (60 mg three times daily), verapamil (120-240 mg daily in divided doses) and amlodipine (5-10 mg once daily) reduce blood pressure predominantly by arteriolar dilatation but also by reducing the force of cardiac contraction. They have proved to be effective antihypertensive agents with only a few side-effects; those that do occur include bradycardia and conduction defects (verapamil and diltiazem), headaches, constipation, flushing and fluid retention. The routine use of calcium antagonists in the treatment of hypertension has been increasing as they prove to be safe and effective drugs.

Main properties of /3·blockers.

Main properties of /3·blockers.

ai-ADRENERGIC ANTAGONISTS such as prazosin (500 to a maximum of 20 mg daily) and doxazosin (1-4 mg daily) are postsynaptic a-blockers that produce vasodilatation and are very effective hypotensive  drugs. Their main complication is marked hypotension following the first dose, especially when the patient is salt-depleted because of previous diuretic therapy. Presynaptic (a,-adrenergic) antagonists such as phentolamine are now used only in combination with f3-blockers in the treatment of phaeochromocytoma. Labetolol (300-600 mg daily in divided doses) is a combined 13- and a-blocker but it has little advantage over 13- blockers.
ACE INHIBITORS such as captopril (50-150 mg daily in divided doses), lisinopril (10- 20 mg daily) and enalapril (10-20 mg daily) block the conversion of angiotensin I to angiotensin II, which is a more powerful vasoconstrictor. ACE inhibitors also block the degradation of bradykinin, which is a vasodilator. Their side-effects include first-dose hypotension and cough. A metallic taste, proteinuria, skin rashes and leucopenia occur generally when they are given in very high doses. The use of ACE inhibitors is increasing as they prove to be safe and effective drugs in the treatment of high blood pressure. ACE inhibitors are particularly useful in diabetics with secondary nephropathy where there is some evidence that proteinuria may be attenuated and they are now the drugs of choice. ACE inhibitors should not be used in the  presence of renal artery stenosis since in this situation the renin-angiotensin system is critical to the maintenance of renal blood flow. Blockade of the production of angiotensin II may result in loss of renal blood flow and infarction of the kidney.
NON-DIURETIC THIAZIDES, including indapamide (2.5 mg daily in the morning) and diazoxide (250- 600 mg i.v. in divided doses), produce vasodilatation but are seldom used. They produce fluid retention and may provoke glucose intolerance.
HYDRALAZINE (up to 150 mg daily in divided doses) and minoxidil (10 mg or more daily; maximum 50 mg) directly dilate the peripheral arterioles, leading to a fall in blood pressure. Hydralazine, when given in doses  greater than 200 mg daily, may provoke a lupus erythematosus- like syndrome, and minoxidil produces fluid retention and an increase in facial and body hair (hypertrichosis) that renders it unsuitable for women. Both drugs are complicated by sinus tachycardia, which may cause uncomfortable palpitations. They are therefore often combined with {3-blockade for the resistant case.
SODIUM NITROPRUSSIDE is effective as an arterial and venous dilator when given intravenously. However, it is inconvenient to use because it must be protected from light to prevent degradation. It is occasionally used for the treatment of hypertensive emergencies
such as disse cting aneurysm.
CENTRALLY ACTING DRUGS such as methyldopa (a false adrenergic transmitter) (750 mg daily in divided doses) and clonidine (an (X2-agonist) (0.1-0.3 mg daily in divided doses) reduce the degree of vasomotor tone.  Both drugs are complicated by tiredness, fluid retention and mild postural hypotension. Methyldopa may also cause a dry mouth, impotence, pyrexia and a positive Coombs’ test. Very rarely, a haemolytic anaemia may be produced. It can also rarely cause chronic active hepatitis. Clonidine may cause depression and it is important that it is not stopped suddenly because severe rebound hypertension may occur.
DEBRISOQUINE, BETHANIDINE AND GUANETHIDINE block postsynaptic adrenergic neurones and are powerful hypotensive drugs. Side-effects include marked postural  hypotension, bradycardia, diarrhoea, nasal congestion, salivary gland pain and inability to ejaculate. Centrally acting drugs and ganglion blockers are rarely used nowadays.

Stepped care for the control of hypertension

The majority of patients with mild or moderate hypertension can be treated as outpatients. The usual practice is to attempt to reduce the blood pressure to about 150/95 mmHg. If general adjustment to life-style and diet have not led to an adequate fall in the blood pressure, it is conventional to prescribe either a {3-blocker or a diuretic. Diuretics (e.g. bendrofluazide 5-10 mg daily) are preferred if heart failure or peripheral vascular disease is present, but {3-blockers (e.g. propranolol 80 mg twice daily or atenolol 100 mg daily) are more suitable if the patient complains of angina. Calcium antagonists such as nifedipine 10 mg twice daily have also been used as a firstline therapy.
If single drug treatment is unsuccessful, it is appropriate to prescribe both a {3-blocker or a calcium antagonist in combination with a diuretic. The combination of {3- blockers and diuretics is particularly attractive because some of their side-effects are partially antagonistic. For example, {3-blockers lead to potassium retention, aggravation of heart failure and decreased renin secretion, whilst thiazide diuretics induce the opposite changes. If these combined therapies are insufficient, more powerful vasodil tors such as hydralazine, prazosin or nifedipine are added to the regimen. ACE inhibitors may be used if these prove inadequate and should always be used with associated diabetes. The hypotensive effect of ACE inhibitors is increased by their use with a diuretic. It is essential that the patient understands that high blood pressure does not go away after a single course of treatment. It is necessary to continue treatment for many years or for life. In addition, the patient’s blood pressure must be checked at regular intervals. Since treatment is lifelong the physician must attempt to simplify treatment regimens to improve compliance. Evidence suggests that poor treatment is better than no treatment at all. Hypertension that is unresponsive to treatment is usually due to the patient not taking the drugs prescribed or to the presence of an underlying primary cause such as coarctation or renal artery stenosis. Such underlying causes must be discovered and corrected before therapy will succeed.

The management of severe or malignant hypertension Patients with severe hypertension (diastolic pressure >130 mmHg), hypertensive encephalopathy or severe complications of hypertension such as left ventricular failure or aortic dissection should be admitted to hospital for urgent treatment of their hypertension under close supervision. It is unwise to reduce the blood pressure too rapidly because cerebral, myocardial or renal infarction may result. The majority of hypertensive emergencies can be treated by slowly (over about 24 hours) bringing the diastolic blood pressure back to 100-110 mmHg. This can normally be achieved by using oral nifedipine (10-20 mg) and {3-blockade, e.g. atenolol 50 mg. When a more rapid fall of blood pressure is needed, e.g. when managing an aortic dissection, intravenous nitroprusside (0.3 f.Lgkg’ min-I) is the agent of choice. Alternatively, chewable nifedipine (5-10 mg), oral captopril (12.5 mg), intravenous diazoxide (bolus of 50 mg over 1 min) or a labeta- 101 infusion (initially 1 mg min-I) may be used.
The management of hypertension during pregnancy Mild hypertension in pregnancy is usual, but more severe hypertension (>140/90 mmHg), associated with proteinuria and peripheral oedema, may be a prelude to eclampsia. Pre-eclampsia is treated with bed rest and hypotensive drugs known to be safe in pregnancy.
Methyldopa, propranolol, atenolol, nifedipine and hydralazine are usually used. Full-blown eclampsia is treated as a hypertensive emergency with intravenous hydralazine. If the high pressure cannot be reduced, the pregnancy may need to be terminated, and this universally reduces the high blood pressure unless the patient had prior high blood pressure.


Patients with untreated malignant or accelerated hypertension have a very poor prognosis-more than 90% will die within the first year. Effective reduction in the blood pressure leads to a dramatic improvement of prognosis. In general, the risk from hypertension depends on:
• Level of blood pressure
• Presence of retinal changes
• Presence of cardiac or renal complications
• Sex of the patient (men are more at risk than women)
• Coexistence of coronary disease and risk factors for
coronary disease such as high plasma lipids, diabetes and smoking
• Age of the patient (young patients fare worse than
the old) The cause of death in hypertensive patients is usually myocardial infarction, cardiac failure, renal failure or cerebrovascular accident. Effective treatment of moderate hypertension clearly improves the prognosis for each of these causes of death. The treatment of even mild hypertension reduces the likelihood of stroke or cardiac failure.

The cardiovascular system in systemic disease

Systemic hypertension

Blood pressure within a population has a skewed distribution, i.e. there is a single peak frequency of blood pressure and there are more individuals with high pressures than low pressures. Different populations have different levels of blood pressure, with those of African origin tending to have higher pressure than Caucasians, i.e. the whole distribution is shifted to the left. The distribution curves for systolic and diastolic blood pressure are similar. Risk of mortality and morbidity rises continuously with increasing blood pressure throughout the range. The rise of risk is not linear, however, being steeper at higher pressures.

Cardiac involvement in some systemic disorders.

Cardiac involvement in some systemic disorders.

The level of blood pressure can be said to be abnormal when it is associated with a clear increase in morbidity and mortality. This level varies with age, sex, race and country. For life insurance reasons and for simple clinical purposes, a diastolic blood pressure in a young adult above 100 mmHg and/or 160 mmHg systolic is taken as definitely hypertensive and a diastolic pressure above 95 mmHg is regarded as probably hypertensive. The World Health Organization have used a definition of 160/95 mmHg, and in Framingham (a small town in Massachusetts, USA), where a very detailed population study is being carried out, 160/95 mmHg was deemed abnormal and 140/90 to 160/95 mmHg was regarded as borderline. The significance of a single elevated reading is unclear and for a firm diagnosis the blood pressure should be elevated on more than one examination. In a proportion of patients the blood pressure increases due to the presence of a doctor (‘white coat hypertension’). In patients without probable target organ damage, some weeks or months can be taken to be sure that the blood pressure is elevated. The blood pressure should be taken twice with the patient in the sitting position and this should be repeated three or four times over several months. When target organ damage is present or the blood pressure reading is very high, a more urgent assessment is needed.

If there is any doubt about the validity of blood pressure measurements taken in the clinic, ambulatory blood pressure monitoring offers a non-invasive assessment during normal daily activities and largely circumvents the problem of ‘white coat hypertension’.


In the large majority of cases no cause can be identified, and this form of hypertension is known as primary or essential. A cause of hypertension can be discovered in less than 10% of patients; such cases are known as secondary hypertension.

Essential hypertension

No single factor has been found to explain essential hypertension; many factors are probably responsible. The blood pressure is determined by the product of the cardiac output and the peripheral vascular resistance. In the early stages of essential hypertension the increase of blood pressure is due to a small increase in cardiac output. This could be due to sympathetic overactivity. Later in the disease, the cardiac output is normal but the peripheral resistance is increased. It is possible that the initial increase in cardiac output induces vascular changes that then sustain and increase the blood pressure. The baroreceptor reflexes operate at a higher pressure in hypertension. An increased blood pressure should stimulate a bradycardia via the carotid sinus baroreceptor mechanism. This does not happen in essential hypertension. This abnormal reflex may be due to the hypertension rather than being its cause.
The causes of essential hypertension include the following.
GENETIC FACTORS. Racial and familial tendencies to high blood pressure are found.
ENVIRONMENTAL FACTORS. Numerous factors have been related to the development of hypertension but only the following appear to be important.
OBESITY. Blood pressure rises with increasing obesity. This relationship persists even when errors of blood pressure measurement in obese subjects (cuff artefact,) are taken into account.
ALCOHOL INTAKE. Ingestion of alcohol acutely raises blood pressure and alcohol intake tends to be higher in individuals with higher pressures. Reduction or withdrawal of regular alcohol intake reduces blood pressure 5-10 mmHg.
SALT INTAKE. There is much controversy about the role of salt in hypertension. There is some evidence of a relationship between the salt intake of an individual and the level of the blood pressure within populations. Similar, but weaker relationships are found between populations. There is less convincing evidence that a moderate reduction of salt intake will reduce blood pressure. Salt intake may increase intravascular volume in the initial stages of the genesis of hypertension, but once peripheral vascular resistance becomes raised, alterations of salt intake may play little part in the regulation of blood pressure.
HUMORAL FACTORS have been implicated in the genesis of hypertension including catecholamines, the reninangiotensin system, and atrial natriuretic peptide. Convincing evidence is lacking that any of these are involved.

Secondary hypertension

This should always be considered in patients with hypertension.In particular, a careful search should be made in hypertensive patients presenting under the age of 35 years. The causes of secondary hypertension can be divided into the following.
RENAL CAUSES. Renal diseases are the most common causes of secondary hypertension, accounting for over 80% of cases. Chronic glomerulonephritis, chronic atrophic pyelonephritis and congenital polycystic kidneys are the conditions usually involved. It may be difficult to determine whether renal disease has caused hypertension or whether the hypertension has produced the renal disease.
The mechanism by which renal disease causes hypertension is probably related to salt and water retention. Occasionally, renal artery stenosis due to fibromuscular hyperplasia or atheroma may cause hypertension (renovascular hypertension) owing to excess renin production.
These include:
• Conn’s syndrome
• Adrenal hyperplasia
• Phaeochromocytoma
• Cushing’s syndrome
• Acromegaly
CARDIOVASCULAR CAUSES. Renovascular hypertension is discussed above.
Coarctation of the aorta (see p. 608) should be considered in young patients with hypertension and a late systolic murmur.
PREGNANCY. Hypertension in the early stages of pregnancy is usually essential hypertension or due to renal disease.
Pre-eclampsia or toxaemia of pregnancy is diagnosed when hypertension develops in the last 3 months of pregnancy and is associated with oedema and proteinuria. The cause of pre-eclampsia is unknown.
Pre-eclampsia may worsen, with the development of severe hypertension, nausea, vomiting, pulmonary oedema and fits. This condition, known as eclampsia, needs urgent treatment.
DRUGS. Oestrogen-containing contraceptives, other steroids, carbenoxolone, liquorice and vasopressin may all cause hypertension. Paroxysms of severe hypertension may occur in patients taking monoamine oxidase inhibitors who eat cheese or other tyramine-containing foods and those who drink wines.


An increase in vascular tone initially accounts for the increased peripheral vascular resistance. As the disease progresses, the walls of small arteries thicken and atheroma develops in larger arteries. Malignant hypertension is characterized by fibrinoid necrosis of the vascular wall. The increased peripheral vascular resistance leads to a greater impedance to left ventricular emptying. Consequently, left ventricular hypertrophy develops. A reduction in renal perfusion pressure can occur, leading to decreased glomerular filtration and reduced sodium and water excretion. The renal changes are described in more detail. The decreased renal perfusion leads to the production of renin, which converts angiotensinogen to angiotensin I. This is changed to angiotensin II, which stimulates the secretion of aldosterone and further contributes to salt and water retention.
Secondary aldosteronism, which occurs with severe or accelerated hypertension and with the use of diuretics, is characterized by high serum levels of aldosterone and renin. In primary aldosteronism (Conn’s syndrome), only the aldosterone is raised. About 10% of patients with essential hypertension have a high plasma renin level, and 25% have a low renin level.
In some cases the pressure rises rapidly and these patients are said to have ‘malignant’ hypertension. Without treatment death occurs within 1-2 years. The accelerated rise in blood pressure produces cerebral oedema, left ventricular failure and severe renal impairment, with proteinuria and microscopic haernaturia Retinal haemorrhages, exudates and papilloedema are also seen and are diagnostic of malignant hypertension.


Hypertension is a risk factor for developing atheroma and patients may therefore develop thrombotic cerebral vascular disease, coronary artery disease and peripheral vascular disease. The increased pressure in the circulation can result in heart failure, cerebral haemorrhage, renal disease and dissecting aortic aneurysms.


The possible causes and consequences of hypertension are assessed. In uncomplicated or essential hypertension, apart from the high blood pressure there are usually no signs, symptoms or abnormal investigations.

The patie!J.t with mild hypertension is usually asymptomatic. Nose bleeds and headaches have been traditionally regarded as possible symptoms, but are probably no commoner than in the general population. There may be a past history of renal disease or a family history of hypertension. Secondary causes of hypertension are suggested by a specific history, such as attacks of sweating and tachycardia in phaeochromocytoma.
Angina may occur either because of associated coronary artery disease or because of the high oxygen demand from hypertrophied muscle. If cardiac failure develops, breathlessness occurs.
Accelerated or malignant hypertension presents with visual impairment, nausea and vomiting, fits, transient paralysis, severe headaches, impairment of consciousness, or symptoms of acute cardiac failure.


In the majority of patients the only sign is the high blood pressure, but in others features of the cause of hypertension may be noted. For example, there may be abdominal bruit due to renovascular obstruction, or delayed femoral pulses due to coarctation of the aorta. Hypertensive heart disease presents with a loud aortic second sound, a prominent left ventricular apical heave and a fourth heart sound. Sinus tachycardia and a third heart sound develop if cardiac failure occurs. Examination of the retina may reveal various abnormalities which are known as Keith-Wagener retinal changes. They are graded as follows:
GRADE I-increased tortuosity of retinal arteries and increased reflectiveness (silver wiring)
GRADE 2 -grade 1 plus the appearance of arteriovenous nipping produced when thickened retinal arteries pass over the retinal veins
GRADE 3 -grade 2 plus flame-shaped haemorrhages and soft ‘cotton wool’ exudates
GRADE 4-grade 3 plus papilloedema (bulging and blurring of the edges of the optic disc)
The presence of haemorrhages, exudates or papilloedema is diagnostic of malignant hypertension which requires urgent treatment.


Routine investigation of a hypertensive patient should always include:
• Chest X-ray
• Echocardiogram
• Urinalysis
• Fasting blood lipids
• Urea, creatinine and electrolytes
If the urea or the creatinine level is abnormal, creatinine clearance, intravenous excretion urography, renal ultrasound and other tests of renal function are necessary. If the tests of renal function or an abnormal bruit suggest a renovascular cause, full renal investigation is essential. If coarctation of the aorta is suspected, digital vascular imaging with intravenous contrast injection or MRI will usually demonstrate the lesion.
If the patient is not taking diuretics, a low serum potassium should suggest an endocrine problem, and aldosterone, cortisol and renin measurements should be performed. A history suggestive of phaeochromocytoma can be investigated with measurement of serum catecholamines or urinary catecholamine metabolites. The chest X-ray may show a large heart and pulmonary congestion if heart failure has developed, or rib notching in coarctation of the aorta. The ECG may show left ventricular hypertrophy or signs of myocardial infarction or ischaemia. Very rarely, ECG features of hyperkalaemia (e.g. with renal failure) or hypokalaemia may be detected.

Pericardial disease

The normal pericardium lubricates the surface of the heart, prevents sudden deformation or dislocation of the heart, and acts as a barrier to the spread of infection.
There are three common presentations of pericardial disease:
1 Acute pericarditis
2 Pericardial effusion
3 Constrictive pericarditis

Acute pericarditis

Inflammation of the pericardium gives rise to chest pain that is substernal and sharp. It may be referred to the neck or shoulders. It is relieved by sitting forward and made worse by lying down and, lilce pleurisy, is aggravated by movement and respiration.
Acute pericarditis has numerous aetiologies, but Coxsackie viral infections and myocardial infarction are the commonest causes in the UK. Viral pericarditis can occur in epidemics. Other aetiologies include uraemia, connective tissue disease, trauma, postpericardiotorny, rheumatic fever, tuberculosis and malignancy.


The cardinal clinical sign is a pericardial friction rub. There is usually a fever when pericarditis is due to viral or bacterial infection, rheumatic fever or myocardial infarction.


During the first week of the illness the ECG shows ST segment elevation, concave upwards, in all leads facing the epicardial surface, i.e. the anterior, lateral and inferior leads. ST segment depression is only seen in the cavity leads (A VR and VI)’ Later, the ST segment falls and T wave inversion develops. As the illness improves the T waves become normal. Cardiac enzymes may be elevated if there is associated myocarditis.

ECGs associated with pericarditis.

ECGs associated with pericarditis.


Treatment consists of anti-inflammatory medication such as oral aspirin, naproxen or indomethacin. Occasionally, if pericarditis is severe or recurrent, systemic corticosteroids may be needed.


Viral pericarditis

This tends to affect young adults and is sudden in onset. Usually, the illness lasts for only a few weeks and the prognosis is good, although sudden deaths do occur. However, recurrences do occur.
Bacterial pericarditis Septicaemia or pneumonia may rarely be complicated by purulent pericarditis. Staphylococcus and Haemophilus influenzae account for two-thirds of such cases. Antibiotics and surgical drainage may be required. This form of pericarditis, especially when due to Staphylococcus, is usually fatal.

Tuberculous pericarditis

This is typified by a chronic low-grade fever, especially in the evening, associated with signs and symptoms of acute pericarditis, malaise and weight loss. Pericardial aspiration may be required to make the diagnosis. The pericardial effusion is usually serous but may be blood-stained. Specific antituberculous chemotherapy is needed.

Uraemic pericarditis

This is often asymptomatic. It usually develops in the terminal stages of uraemia. Pericarditis following myocardial infarction A pericardial friction rub and the recurrence of chest pain and fever occurs in about 20% of patients during the first few days after myocardial infarction, especially anterior wall infarction.

Dressler’s syndrome

This is pericarditis occurring 1 month to 1 year after an acute myocardial infarction.

Malignant pericarditis

Carcinoma of the bronchus, carcinoma of the breast and Hodgkin’s disease are the most common tumours to infiltrate the pericardium. Leukaemia and malignant melanoma are also associated with pericarditis.
Pericardiocentesis may be useful in diagnosing the malignancy.

Pericardial effusion

Although acute pericarditis is initially dry and fibrinous, almost all aetiologies of this inflammatory reaction also induce the formation of a pericardial effusion. The effusion collects in the closed pericardium. When the pericardium can distend no more, it may produce mechanical embarrassment to the circulation by preventing ventricular filling; this is called cardiac tamponade.


The clinical features include a raised jugular venous pressure, with sharp diastolic collapse-y descent (Friedreich’s sign), a paradoxical pulse (the blood pressure falls during inspiration), increased neck vein distension during inspiration (Kussmaul’s sign) and reduced cardiac output. Because of the effusion, the apex beat may not be palpable and heart sounds are soft. Although a friction rub is often heard, it may be quieter than before the fluid accumulated as the effusion separates the visceral from the parietal pericardium.


The ECG shows reduced voltages, and the chest X-ray may demonstrate an increasingly large globular heart with sharp outlines. The pulmonary veins are typically not distended. Echocardiography is the most useful technique for demonstrating a pericardial effusion.


When the effusion collects rapidly and the circulation is embarrassed, the effusion must be tapped. Pericardiocentesis is also indicated when a malignant, tuberculous or a purulent effusion is suspected. In the UK, malignancy is the most common cause of reaccumulation of pericardial effusion. Reaccumulation may require pericardial fenestration, i.e. the creation of a pericardial window, either transcutaneously via a balloon pericardiotomy under local anaesthesia or using a conventional surgical approach.

Constrictive pericarditis

Following tuberculous pericarditis, haemopericardium, or acute pericarditis due to viral infection, bacterial infection or rheumatic heart disease, the pericardium may become thick, fibrous and calcified. The heart is then encased in a solid shell and cannot fill properly.


There are signs of systemic venous congestion, i.e. ascites, dependent oedema, hepatomegaly and jugular venous distension, without much breathlessness or pulmonary venous distension. There are also signs of impaired ventricular filling, i.e. Kussmaul’s sign, Friedreich’s sign and pulsus paradoxus.
Atrial fibrillation is common (30%) and a loud heart sound, called a pericardial knock, due to rapid ventricular filling may be heard. This is an early third heart sound. Other causes of ascites must be excluded.


The chest X-ray shows a relatively small heart with obvious calcification seen on the lateral film and using fluoroscopy.
The ECG shows low QRS voltages and T wave inversion, and the echocardiogram will demonstrate the thickened pericardium and the relative immobility of the heart. CT is also good at detecting thickness and calcification of the pericardium.


Treatment involves the surgical removal of a substantial proportion of the pericardium. About half the patients do well, but in the others persistent constriction, atrial fibrillation and myocardial disease prevent full recovery.

Myocardial disease

Myocardial disease that is not due to a specific heart  muscle disorder or a known infiltrative, metabolic/toxic or neuromuscular disorder may be caused by:
• An acute or chronic inflammatory pathology (myocarditis)
• Idiopathic myocardial disease (cardiomyopathy)


Myocarditis, whether idiopathic or infective, is the most common form of inflammatory endomyocardial disease. A definitive aetiology with isolation of viruses or bacteria is uncommon. Causative factors include: VIRUSEs, particularly Coxsackie, influenza, rubella, polio, adenovirus and echovirus.
PROTOZOA, e.g. Trypanosoma cruzi, which causes Chagas’ disease and is endemic in central and South America, and Toxoplasma gondii-a common cause of myocarditis in the newborn or in immunologically compromised adults.
RADIATION, CHEMICALS AND DRUGS, e.g. lead poisoning, emetine and chloroquine,
BACTERIAL INFECTION, e.g. diphtheria, which is due to an exotoxin produced by Corynebacterium, Rickettsia, Chlamydia, Coxiella (the causative agent of Q fever).


Patients present with an acute illness, often characterized by fever and cardiac failure. There may be a history of previous respiratory or febrile illness. Physical examination reveals soft heart sounds, a prominent third sound and tachycardia (gallop rhythm). Often a pericardial friction rub may be heard.


CHEST X-RAY may show some cardiac enlargement, depending on the stage and virulence of the disease. THE ECG demonstrates ST and T wave abnormalities and arrhythmias. Diphtheritic myocarditis may induce heart block, and Chagas’ disease produces both heart block and ventricular tachyarrhythmias.
CARDIAC ENZYMES are elevated.
CARDIAC BIOPSY shows acute inflammation.
VIRAL ANTIBODY TITRES may be increased.


General management includes bed rest and the eradication of any acute infection. Therapy is directed towards the management of cardiac failure and the treatment of cardiac arrhythmias. Depending on the aetiology, the prognosis is usually good, although a chronic cardiomyopathy may occasionally ensue.


These idiopathic conditions are classified according to their clinical presentation as:
1 Dilated cardiomyopathy-ventricular dilatation
2 Hypertrophic cardiomyopathy-myocardial hypertrophy
3 Restrictive cardiomyopathy-impaired ventricular filling

Dilated cardiomyopathy (oeM)

DCM is characterized by dilatation and impaired systolic function of the left ventricle and/or right ventricle. The aetiology of idiopathic DCM is unknown. The frequency of the ACE DD genotype is higher than matched controls suggesting that ACE gene variants may contribute to the pathogenesis. There is also an association with viral (Coxsackie) infection and an immunemediated pathogenesis is likely. Many cases of systemic heart muscle disease present with clinical features of DCM and they include:
CARDIOVASCULAR DISEASE (ischaemic, rheumatic, congenital, systemic hypertension)
GENERALIZED DISEASE, e.g. haemochromatosis, sarcoidosis
CONNECTIVE TISSUE DISORDERS, e.g. systemic lupus erythematosus, systemic sclerosis
NEUROMUSCULAR DISEASE, e.g. muscular dystrophy, Friedreich’s ataxia
GLYCOGEN STORAGE DISEASE, e.g. Pornpe’s disease


CYTOTOXIC DRUG THERAPY, e.g. doxorubicin, cyclophosphamide


Symptoms depend on the relative degree of right and left heart failure and the incidence of cardiac arrhythmias and emboli.
Physical signs reflect heart failure, i.e. cardiomegaly, tachycardia, jugular venous pressure elevation, third or fourth heart sounds and basal crackles. Ventricular dilatation leads to functional mitral or tricuspid valvular regurgitation.


CHEST X-RAY demonstrates generalized cardiac enlargement THE ECG shows diffuse non-specific ST segment and T wave changes. Conduction disturbances, sinus tachycardia and arrhythmias (such as atrial fibrillation, ventricular premature contractions or ventricular tachycardia) may also be seen.
THE ECHOCARDIOGRAM reveals dilatation of the left ventricle and/or right ventricle with poor global contraction.
CARDIAC BIOPSY shows variable fibrosis and nonspecific leucocyte infiltration. Infiltrative disorders (e.g. amyloid) may be detected in specific cases.


Management involves the conventional treatment of heart failure and arrhythmias. A history of embolization is an indication for anticoagulant treatment. Prolonged bed rest, corticosteroid therapy, the avoidance of alcohol, and nutritional supplements may be indicated in special cases. Metoprolol has been shown to improve haemodynamic and clinical function in some patients. Severe congestive cardiomyopathy in relatively young adults is treated with cardiac transplantation.

Two-dimensional (apical four-chamber view) and M-mode echocardiograms

Two-dimensional (apical four-chamber view) and M-mode echocardiograms

Hypertrophic cardiomyopathy (HeM)

Also known as hypertrophic obstructive cardiomyopathy (HOCM), this is characterized by marked hypertrophy of the left and/or right ventricle, particularly the interventricular septum in the absence of a cardiac or systemic cause. The hypertrophied muscle results in distorted left ventricular contraction and abnormal mitral valve movement during systole. Some degree of mitral regurgitation may develop. Apposition of the anterior cusp of the mitral valve to the hypertrophied septum may cause some obstruction to left ventricular emptying. About half of the cases of HCM are familial and due to a genetic disorder of cardiac f3-myosin heavy chain (f3MHC). In the families with a high instance of sudden death, there is an increased frequency of ACE gene polymorphism (DD) (see p. 110). It has been suggested that allele D, which is associated with increased plasma ACE levels, interacts with growth regulators, e.g. c-myc. Thus the high frequency of allele D and different f3MHC mutations may account for the variable clinical presentations of HCM. The aetiology is unknown in sporadic cases. The failure of hypertrophy to manifest before completion of the adolescent growth phase may make diagnosis difficult in children.


Patients with this condition may present with syncope or presyncope (typically exertional), angina, cardiac arrhythmias or sudden death. As with other cardiomyopathies, dyspnoea due to left ventricular failure is a common but late presentation. In this case left ventricular failure is not due to the failing contractile function of the myocardium; instead, it is due to the inability of the heart muscle to relax. Thus, left ventricular filling and therefore left ventricular emptying are impaired.
The classical physical findings are:
DOUBLE APICAL PULSATION (forceful atrial contraction produces a palpable fourth heart sound)
JERKY CAROTID PULSE because of rapid ejection and sudden obstruction to left ventricular outflow during asystole
EJECTION SYSTOLIC MURMUR because of left ventricular outflow obstruction late in systole that can be increased by physical manoeuvres, e.g. Valsalva, squatting
PAN-SYSTOLIC MURMUR due to mitral regurgitation


CHEST X-RAY is usually unremarkable.
THE ECG demonstrates left ventricular hypertrophy and ST and T wave changes.
THE ECHOCARDIOGRAM is diagnostic because it shows septal hypertrophy (greater than the hypertrophy of the posterior wall), abnormal mitral valve movement and a very vigorously contracting ventricle.


Firstly, sudden death must be avoided by antiarrhythmic treatment. Long-term amiodarone treatment is effective. Syncope or chest pain may be treated with f3-blockade. Vasodilators should be avoided because they may aggravate left ventricular outflow obstruction owing to peripheral venous blood pooling. Occasionally, resection of septal my ocardium may be indicated.

Restrictive cardiomyopathy

Some cardiomyopathies do not present with muscular hypertrophy or ventricular dilatation. Instead, ventricular filling is restricted (as with constrictive pericarditis). Conditions associated with this form of cardiomyopathy are amyloidosis, sarcoidosis, Loeffler’s endocarditis and endomyocardial fibrosis; in the latter two conditions there is myocardial and endocardial fibrosis associated with eosinophilia. Thrombus formation is common in restrictive cardiomyopathy.


Dyspnoea, fatigue and embolic symptoms may be the presenting features. Restriction to ventricular filling also results in persistently elevated venous pressures and consequent hepatic enlargement, ascites and dependent oedema.
Physical signs are similar to those of constrictive pericarditis, i.e. a high jugular venous pressure with diastolic collapse (Friedreich’s sign) and elevation of the jugular venous pressure with inspiration (Kussmaul’s sign). Cardiac enlargement with a third or fourth heart sound is common.


CHEST X-RAY confirms the cardiac enlargement. THE ECG usually has low-voltage and ST segment and T wave abnormalities.
THE ECHOCARDIOGRAM shows symmetrical myocardial thickening and a normal systolic ejection fraction, but impaired ventricular filling.
TRANSVENOUS ENDOCARDIAL BIOPSY may be useful for more detailed diagnosis.


There is no specific treatment. Cardiac failure and embolic problems should be treated. Cardiac transplantation should be considered in some severe cases.

Atrial myxoma

This is the commonest primary cardiac tumour. A myxoma usually develops in the left atrium and is a polypoid, gelatinous structure attached by a pedicle to the atria septum. The tumour may obstruct the mitral valve or may be a site of thrombi that then embolize. It is also associated with constitutional symptoms: the patient may present with dyspnoea, syncope or a mild fever. The most important physical signs are a loud first heart sound, a tumour ‘plop’ (a loud third heart sound produced as the pedunculated tumour comes to an abrupt halt), a middiastolic murmur, and signs due to embolization. A raised ESR is usually present.
The diagnosis is easily made by echo cardiography because the tumour is demonstrated as a dense spaceoccupying lesion. Surgical removal usually results in a complete cure.
Myxomas may also occur in the right atrium or in the ventricles. Other primary cardiac tumours include rhabdomyomas and sarcomas.

Two-dimensional echocardiogram

Two-dimensional echocardiogram

Pulmonary heart disease

Pulmonary hypertension

An elevated pulmonary arterial pressure, known as pulmonary hypertension, has numerous causes: CHRONIC LUNG DISEASE, which is diagnosed clinically and by abnormalities of lung function. INCREASED PULMONARY BLOOD FLOW because of leftto- right shunting through a VSD, ASD or PDA.
LEFT VENTRICULAR FAILURE, MITRAL VALVE DISEASE, LEFT ATRIAL TUMOUR OR THROMBUS, OR PULMONARY VENO-OCCLUSIVE DISEASE, which cause an elevation in the pulmonary arterial pressure secondary to an elevation of the pulmonary venous and pulmonary capillary pressure; the pulmonary wedge pressure is elevated in these cases.
PULMONARY THROMBOEMBOLIC DISEASE. PRIMARY PULMONARY HYPERTENSION, a rare condition seen predominantly in young women. Its aetiology is unknown but recurrent small pulmonary emboli, pulmonary vasoconstriction due to neural, humoral factors or drugs (e.g. oral contraceptives, Crotalaria teas and the appetite suppressant fenfluramine), connective-tissue disease and familial causes have all
been suggested.
Pulmonary hypertension leads to enlarged proximal pulmonary arteries, right ventricular hypertrophy and right atrial dilatation. The pulmonary arterial changes depend on the aetiology of the pulmonary hypertension. Multiple peripheral pulmonary arterial stenoses can produce a syndrome that is similar to pulmonary hypertension, but the pressure in the distal pulmonary bed is normal or low.


Chest pain, exertional dyspnoea, syncope and fatigue are common symptoms, and sudden death may occur. Other sympoms are due to the cause of the pulmonary hypertension. On physical examination there is a prominent a wave in the jugular venous pulse, a right ventricular (parasternal) heave and a loud pulmonary component to
the second heart sound. Other findings include a right ventricular fourth heart sound, a systolic pulmonary ejection click, a mid-systolic ejection murmur and an early diastolic murmur due to pulmonary regurgitation (Graham Steell murmur). If tricuspid regurgitation develops, there is a pan-systolic murmur and a large jugular v wave.


The chest X-ray may show right ventricular enlargement and right atrial dilatation. The pulmonary artery is usually prominent and the enlarged proximal pulmonary arteries taper rapidly. Peripheral lung fields are oligaemic. The ECG demonstrates right ventricular hypertrophy (right axis deviation, possibly a predominant R wave in
lead VI> and inverted T waves in right precordial leads) and a right atrial abnormality (tall peaked P waves in lead II).
Other investigations are performed to evaluate the cause of pulmonary hypertension. It is particularly important to look for treatable conditions such as leftto- right shunts, mitral stenosis or left atrial tumours with echocardiography. Radioisotope lung scans and sometimes open lung biopsy are performed, e.g. in young patients with severe pulmonary hypertension of unknown cause. Pulmonary angiography is dangerous and is rarely necessary.


Treatment is determined by the condition underlying pulmonary hypertension. Primary pulmonary hypertension is treated with anticoagulation (because of the possibility of recurrent thromboembolism). Diuretic treatment may be used for right ventricular failure, but care should be taken to avoid reduction of the left ventricular filling pressure. Hypoxia is avoided by the use of oxygen therapy when necessary. Vasodilators including calcium antagonists such as verapamil and prostacyclins have been tried, but with little long-term success. Usually there is a progressive downhill course. Heart and lung transplantation is recommended for young patients. Pulmonary embolism (acute cor pulmonale)
Thrombus, usually formed in the systemic veins or rarely in the right heart, may dislodge and embolize into the pulmonary arterial system. Post-mortem studies indicate that this is a very common condition (microemboli are found in up to 60% of autopsies) but it is not usually diagnosed this frequently in life. Ten per cent of clinical pulmonary emboli are fatal.
Conditions leading to the formation of clot in the systemic veins (and hence predisposing to pulmonary emboli) include prolonged bed rest, pelvic and lower limb fractures, pelvic or abdominal surgery, cardiac failure, pregnancy and childbirth, oral contraceptive drugs, malignant disease, chronic pulmonary disease and hypercoagulable states.
Atrial fibrillation may allow thrombus formation in the right atrium, and septal or right ventricular infarction may favour thrombosis in the right ventricle. A small proportion (less than 10%) of pulmonary emboli are due to these cardiac causes.
After pulmonary embolism, lung tissue is ventilated but not perfused, resulting in impaired gas exchange. After some hours surfactant is no longer produced by the non-perfused lung, alveolar collapse occurs and hypoxaemia is the result. The haemodynamic consequence of pulmonary embolism is an elevation of pulmonary arterial pressure and a reduction in cardiac output. The zone of lung that is no longer perfused by the pulmonary artery may infarct but often does not do so because oxygen continues to be supplied by the bronchial circulation and the airways.

A 12-lead ECG demonstrating

A 12-lead ECG demonstrating


A small embolus may present with effort dyspnoea, tiredness, syncope and, occasionally, cardiac arrhythmias. A medium-sized embolus leading to pulmonary infarction can present with sudden onset of pleuritic pain, cough with haemoptysis, and dyspnoea. A massive pulmonary embolus presents as a medical emergency: the patient has severe central chest pain and suddenly becomes shocked, pale and sweaty, with marked tachypnoea and tachycardia. Syncope may result if the cardiac output is transiently but dramatically reduced.

Death may follow rapidly

Physical signs vary according to the size of the embolus and the occurrence of pulmonary infarction: A SMALL EMBOLUS may reveal no abnormal signs apart from a few basal crackles.
LARGE EMBOLI lead to a right ventricular heave, a gallop rhythm, tachycardia and a prominent a wave in the jugular venous pulse. The second heart sound may be loud because of pulmonary hypertension or soft if the cardiac output is very reduced. Continuous (systolic and diastolic) murmurs may be generated by turbulent blood flow around the embolic obstructions.

WITH PULMONARY INFARCTION, a pleural rub and pyrexia may also be present. DEEP VENOUS THROMBOSIS. Although a clinical deep venous thrombosis is not commonly observed, a detailed investigation of the lower limb and pelvic veins will reveal thrombosis in more than half of the cases.


The chest X-ray is often normal but the abrupt cut-off of a pulmonary artery or a translucency of an underperfused distal zone is occasionally seen. Later, atelectasis leads to opacities. An infarction may be visualized as a wedgeshaped opacity adjacent to the pleural edge, a pleural effusion and a raised hemidiaphragm. Past infarcts may be seen as opaque linear scars.

The ECG is usually normal except for sinus tachycardia. In relatively severe cases, however, right atrial dilatation produces tall, peaked P waves in lead II, and right ventricular hypertrophy and dilatation give rise to right axis deviation, some degree of right bundle branch block and T wave inversion in the right precordial leads.

The classical pattern of an S wave in lead I and a Q wave and inverted T waves in lead III (Sl, Q3, T3), which reflects right ventricular ‘strain’, is not usually present.

If pulmonary infarction has occurred, there will be a polymorphonuclear leucocytosis, an elevated ESR and increased lactate dehydrogenase levels.

Pulmonary embolism usually results in arterial hypoxaemia and hypocapnia. A pulmonary technetium-99m scintigram may demonstrate underperfused areas . The specificity of this technique is greatly improved when combined witha ventilation scintigram performed after inhalation of radioactive xenon gas . The finding of a non perfused but ventilated zone is more suggestive of pulmonary embolism.

Pulmonary angiography is sometimes undertaken if surgery is considered in acute massive embolism. The test is performed by injecting contrast material through a catheter inserted into the main pulmonary artery. Filling defects or obstructed vessels can be delineated. Angiography is hazardous but the risk may be reduced if contrast is injected into each pulmonary artery separately. If the patient is in extremis and the diagnosis is obvious, surgery should proceed without prior angiography.

A 12-lead ECG

A 12-lead ECG

Ventilation (top) and perfusion

Ventilation (top) and perfusion


Prevention of further emboli The basis of therapy is intravenous heparin, starting with a bolus of 10000U and followed by the continuous infusion of 1000-2000 U hour:”. Oral anticogulant are usually begun after 48 hours and the heparin is tapered off as the oral anticoagulant becomes efftective Oral anticoagulants are continued for 6 months, depending on the likelihood of recurrcess  0f venous thrombosis or embolism.

Contrast injected directly

Contrast injected directly

Dissolution of the thrombus

Fibrinolytic therapy such as streptokinase (250000 U by i.v. infusion over 30 min, followed by streptokinase 100000 U i.v, hourly) is often used fo following a major embolism. It may also be given into the pulmonary artery.


Surgical embolectomy is rarely necessary, but when the haemodynamic circumstances are very severe there may be no alternative. Inferior vena caval interruption or plication, or the insertion of a filter into the inferior vena cava, may occasionally be necessary if anticoagulant or fibrinolytic therapy is contraindicated or fails to prevent recurrences of pulmonary embolism.

Chronic cor pulmonale

Cor pulmonale is the commonest variety of pulmonary hypertensive heart disease.


PATHOPHYSIOLOGY Pulmonary vascular resistance is increased because of effective loss of pulmonary tissue and because of pulmonary vasoconstriction caused by hypoxia and acidosis. The increased pulmonary vascular resistance leads to pulmonary hypertension, which initially occurs only during an acute respiratory infection. Eventually, the pulmonary hypertension becomes persistent and progressively more severe. The pulmonary vascular bed is gradually obliterated by muscular hypertrophy of the arterioles and thrombus formation. Right ventricular function is progressively compromised because of the increased pressure load. Hypoxia further impairs right ventricular function, and, as it develops, left ventricular function is also depressed.


The clinical features are those of pulmonary hypertension and right ventricular failure occurring in patients with chronic chest disease. The dominant clinical picture  depends on the type of lung disease.


Vigorous therapy of the pulmonary condition may lead to marked improvement of blood gases and consequent improvement of the heart failure. Acute chest infections must be treated promptly. Oxygen therapy over a long period may reduce established pulmonary hypertension, with improvement in overall prognosis. Any heart failure should be treated. Extensive surgical removal of organized thrombus may be considered.

Causes of cor pulmonale.

Causes of cor pulmonale.