Pericardial diseases – classification. Pericarditis. Pericardiac tamponade.

At a glance

1. The pericardium is a two-layered sac around the heart. Its diseases are pericarditis (acute, incessant, recurrent or chronic), pericardial effusion and tamponade, and constrictive pericarditis.
2. Most acute pericarditis in Europe is viral or idiopathic. It causes sharp chest pain that is eased by sitting forward, a friction rub, widespread ST elevation with PR depression and often a small effusion.
3. Aspirin or an NSAID with colchicine treats it, and colchicine halves the risk of recurrence. Corticosteroids are kept for specific indications, because they make recurrences more likely.
4. Fever above 38 °C, a subacute onset, a large effusion or failure to respond to treatment suggest a specific cause, such as tuberculosis or cancer, and call for admission.
5. Cardiac tamponade, fluid under pressure that stops the heart filling, is an emergency: hypotension, a raised JVP and pulsus paradoxus, treated by draining the fluid. It depends on how fast the fluid gathers more than on how much there is.
6. Constrictive pericarditis, a stiff, scarred pericardium, presents with right-sided heart failure, Kussmaul's sign and a pericardial knock, and is treated by removing the pericardium.

01Definition and overview

The pericardium is a double-layered sac: an outer fibrous layer and an inner serous one, whose visceral layer covers the heart (the epicardium) and folds back to line the fibrous sac as the parietal layer. Between the two serous layers lie 20 to 50 mL of fluid that lets the heart move freely. The pericardium holds the heart in place, protects it, and limits its acute dilatation.

The pericardial syndromes:

• Pericarditis, inflammation of the pericardium, described by its course:
  • acute, with symptoms for up to 4 weeks;
  • incessant (subacute), with symptoms that persist beyond 4 weeks, up to 3 months, without a clear remission despite full treatment, including relapses while the drugs are being tapered;
  • recurrent, a new attack after a documented remission and after all anti-inflammatory drugs have been stopped;
  • chronic, lasting more than 3 months.
• Pericardial effusion, fluid in the sac, and cardiac tamponade, an effusion under enough pressure to stop the heart filling.
• Constrictive pericarditis, a thickened, stiff pericardium that restricts filling, and its mixed form, effusive-constrictive pericarditis, in which the right atrial pressure stays high after the fluid is drained because the visceral pericardium constricts.
• Pericardial masses (cysts and tumours) and congenital absence of the pericardium, both rare.

Pericarditis and myocarditis often occur together. They are grouped under the term inflammatory myopericardial syndrome while the diagnosis is being made: myopericarditis is mainly pericarditis with raised troponin but normal ventricular function, and perimyocarditis is mainly myocarditis with impaired ventricular function.

02Etiology and pathophysiology

Causes

In high-income countries acute pericarditis is idiopathic or presumed viral in over 80 per cent of outpatients and about half of patients in hospital. In low-income countries, and particularly in sub-Saharan Africa where it is linked to HIV, tuberculosis is the commonest cause.

What goes wrong

• Inflammation roughens the serous layers, which rub against each other (the friction rub) and hurt, and exudate collects as an effusion. Inflammation of the outer myocardium explains the ST changes and the raised troponin in some patients. Recurrent pericarditis is driven largely by the innate immune system, through interleukin-1, which is why IL-1 blockers work.
• The pericardium stretches slowly but not quickly. Its pressure-volume curve is flat at first and then steep, so 200 to 300 mL gathering in minutes, as with bleeding into the sac, can cause tamponade, while 1 to 2 litres gathering over weeks may cause none.
• In tamponade, the pressure in the sac rises above the filling pressure of the right heart, then the left. The chambers collapse in diastole, the stroke volume falls, and the circulation depends on tachycardia and a high venous pressure. On inspiration the right ventricle fills more and pushes the septum into the left ventricle, so the left ventricular output and the systolic pressure fall: pulsus paradoxus.
• In constriction, the stiff pericardium allows rapid filling early in diastole and then stops it abruptly. The diastolic pressures in all four chambers rise and equalise, and the changes in pressure in the chest on breathing no longer reach the heart, which explains Kussmaul's sign and the respiratory variation in filling.

03Clinical features

Acute pericarditis

• Chest pain, sharp and pleuritic, behind the sternum and sometimes to the trapezius ridge, worse lying flat, on breathing in and on coughing, and eased by sitting forward.
• A pericardial friction rub, a scratchy sound best heard at the left sternal edge with the patient leaning forward, which comes and goes and is heard in about a third of patients.
• Fever, usually low-grade, and a preceding viral illness.

Pericardial effusion and tamponade

A slowly gathering effusion may cause no symptoms, or breathlessness, a feeling of fullness and, when large, compression of nearby structures: cough, hoarseness, hiccups or difficulty swallowing. The heart sounds are quiet and the apex beat hard to feel, and a large effusion can compress the left lung base (Ewart's sign).

Tamponade adds:

• tachycardia, hypotension and cold extremities, with breathlessness and a patient who wants to sit up;
• a raised JVP with a prominent x descent and an absent y descent;
• pulsus paradoxus, a fall in systolic pressure of more than 10 mmHg on inspiration;
• quiet heart sounds. With hypotension and a raised JVP they make Beck's triad, which is classically seen when tamponade develops quickly.

Constrictive pericarditis

The patient has right-sided heart failure that seems out of proportion to the size of the heart: a raised JVP with a steep y descent (Friedreich's sign), which rises on inspiration (Kussmaul's sign), hepatomegaly and ascites often more striking than the leg swelling, fatigue, and a pericardial knock, an early diastolic sound. Atrial fibrillation is common. Constriction is often mistaken for liver disease.

04Diagnosis and management

Diagnosing acute pericarditis

The diagnosis is clinical. European criteria count typical chest pain as the entry point and then look for:

• a pericardial friction rub;
• widespread ST elevation or PR depression on the ECG;
• a raised CRP;
• a new or growing pericardial effusion;
• pericardial oedema or late gadolinium enhancement on cardiac MRI.

Pericarditis is definite with typical pain and at least two of these, and possible with one.

The tests in every patient:

• ECG: widespread concave ST elevation and PR depression, with the reverse in aVR, evolving over days to T wave inversion. These typical changes are present in only about half to 60 per cent of patients, and because the pericardium itself is electrically silent, they reflect inflammation of the outer myocardium.
• Blood tests: CRP and the white cell count, which also follow the response; troponin, raised in 20 to 30 per cent, which means myopericarditis; renal and thyroid function.
• A chest X-ray and echocardiography for an effusion and for ventricular function.
• Cardiac MRI or CT when the diagnosis is uncertain, when myocarditis is suspected or the course is complicated.
• Specific tests where the history points: tuberculosis tests, autoantibodies, tests for cancer, and analysis of the pericardial fluid (cells, cytology, culture, adenosine deaminase for tuberculosis).

The main differential is an acute coronary syndrome, which the distribution of the ST changes, their reciprocal depression, the troponin and the echocardiogram separate. Aortic dissection, pulmonary embolism and pneumothorax also cause sudden chest pain.

Treating acute pericarditis

Patients with a high-risk feature are admitted and a cause is sought: fever above 38 °C, a subacute onset over days, a large effusion (more than 20 mm) or tamponade, no response to anti-inflammatory treatment after a week, myocardial involvement (a raised troponin), immunosuppression, trauma or treatment with anticoagulants. Incessant and effusive-constrictive pericarditis are also high-risk. The others can be treated at home.

• Aspirin (750 to 1000 mg every 8 hours) or ibuprofen (600 mg every 8 hours), for 1 to 2 weeks and then tapered, with a proton pump inhibitor. Aspirin is chosen in patients who take it already, such as after an infarction.
• Colchicine, 0.5 mg twice a day, or once a day in patients who weigh 70 kg or less, for at least 3 months, and at least 6 months for recurrences. It is stopped last, once the remission is stable.
• Corticosteroids are not a first choice: they make recurrence more likely, especially at high doses and with fast tapering. They are used at low to moderate doses with colchicine when NSAIDs are contraindicated or ineffective, and in autoimmune disease, pregnancy and kidney failure. In pregnancy NSAIDs are used only up to 20 weeks, while low-dose prednisone and colchicine can be continued.
• Exercise beyond everyday activity is restricted for at least a month and until remission (no symptoms and a normal CRP), in athletes and non-athletes alike.

Recurrent pericarditis is treated with colchicine for 6 months or more together with an NSAID or low-dose corticosteroid, and tapers slowly, guided by the CRP. Patients who depend on corticosteroids and do not respond to colchicine, with a raised CRP, are given an interleukin-1 blocker, anakinra or rilonacept. In a trial of rilonacept, 7 per cent of patients who stayed on it had a recurrence against 74 per cent of those switched to placebo. Azathioprine, intravenous immunoglobulin and pericardiectomy are kept for the rare refractory cases.

Specific causes have their own treatment: six months of standard four-drug antituberculous treatment for tuberculous pericarditis, with adjunctive corticosteroids considered in HIV-negative patients because they reduce constriction; surgical drainage and antibiotics for purulent pericarditis; dialysis for uraemic pericarditis.

Effusion and tamponade

Echocardiography measures the effusion (mild under 10 mm, moderate 10 to 20 mm, large over 20 mm in diastole) and looks for signs of tamponade: collapse of the right atrium in late diastole and of the right ventricle in early diastole, a dilated inferior vena cava that does not narrow on inspiration, and large swings with breathing in the flow through the mitral and tricuspid valves. The ECG shows sinus tachycardia, low voltage and electrical alternans, the swinging of the heart in the fluid. The chest X-ray shows a large, globular heart with clear lung fields.

Tamponade is treated by draining the fluid at once: pericardiocentesis, a needle and drain placed under echocardiographic or fluoroscopic guidance, or surgical drainage when the fluid is purulent, loculated or clotted, or the cause is bleeding from trauma, aortic dissection or a ruptured ventricle. Fluids help briefly in a patient who is volume depleted. Diuretics, vasodilators and, where possible, positive-pressure ventilation are avoided, because they reduce the filling the heart depends on.

Drainage is also used to find the cause of an effusion (suspected tuberculosis, bacterial infection or cancer) and for symptomatic moderate or large effusions that persist despite medical treatment. A large, chronic, idiopathic effusion that causes no symptoms is watched rather than drained. Effusions that keep returning, usually from cancer, are treated with a pericardial window, which lets the fluid drain into the pleural space or the abdomen.

Constriction

• Chest X-ray: pericardial calcification in some patients, best seen on a lateral film; the heart is not enlarged.
• Echocardiography: a septal bounce in early diastole, swings in filling with breathing, a dilated inferior vena cava and normal or brisk relaxation of the mitral annulus.
• CT and cardiac MRI: a pericardium 4 mm thick or more, sometimes calcified, though thickness can be normal; inflammation on MRI suggests constriction that may still respond to treatment.
• Cardiac catheterisation: equal diastolic pressures in all four chambers, a "dip and plateau" (square root) pattern in the ventricular pressure, and right and left ventricular systolic pressures that move in opposite directions with breathing.

The main differential is restrictive cardiomyopathy, a stiff myocardium. A thick pericardium, a septal bounce and opposite ventricular pressure swings favour constriction; a thick, infiltrated myocardium, a high BNP and slow relaxation on echocardiography favour restriction.

About 1 in 10 patients with acute pericarditis develops a transient constriction, which resolves with anti-inflammatory treatment, so newly diagnosed constriction with signs of inflammation is treated medically for 3 to 6 months first. Chronic constriction is treated with pericardiectomy, removing as much pericardium as possible, in a centre that does many, and repairing a severely leaking tricuspid valve at the same time. It carries an operative mortality of several per cent, higher after radiation and in advanced disease, so it is best done before the myocardium wastes. Diuretics ease the congestion until then. In tuberculous constriction, antituberculous treatment comes first, and surgery follows if the patient does not improve within 4 to 8 weeks.

05Epidemiology

Acute pericarditis causes about 5 per cent of emergency attendances for chest pain and about 0.2 per cent of cardiovascular admissions. It is commoner in men and in young and middle-aged adults. About 15 to 30 per cent of patients have a recurrence after a first episode without colchicine, and up to half after a first recurrence. Tuberculosis causes most pericarditis and most effusions in sub-Saharan Africa and parts of Asia. In Europe up to half of large effusions and of cases of constriction remain idiopathic; cancer, infections and procedures cause most other large effusions, and cardiac surgery and radiotherapy much of the other constriction.

06Prognosis

Idiopathic and viral pericarditis has a good outlook: most patients recover within weeks, tamponade is rare and constriction develops in under 1 per cent. Recurrences are distressing and may continue for years, but they seldom lead to tamponade or constriction. The risk of constriction depends on the cause: about 2 to 5 per cent after autoimmune and cancer-related pericarditis, and 20 to 30 per cent after tuberculous and purulent pericarditis.

The outlook of an effusion depends on its cause, and malignant effusions carry the prognosis of the cancer. Untreated tamponade is fatal, while drainage brings immediate relief. After pericardiectomy for constriction, most patients improve, but survival is lower after radiation-induced constriction and in patients with impaired ventricles or kidneys.

Check yourselfAnswer, then say how sure you were: a lucky guess still counts as a weak point.

1Which ECG is typical of acute pericarditis?

ST elevation in II, III and aVF with ST depression in I and aVLDeep Q waves in the anterior leadsWidespread concave ST elevation with PR depression, and ST depression with PR elevation in aVRLow voltage QRS complexes that alternate in height from beat to beat

2In a first episode of acute idiopathic pericarditis, what does adding colchicine to aspirin or ibuprofen achieve?

It removes the need for the anti-inflammatory drugIt prevents cardiac tamponadeIt is useful only once the pericarditis has recurredIt roughly halves the risk of incessant or recurrent pericarditis

3A day after a coronary procedure, a man becomes hypotensive and tachycardic, with a raised JVP and quiet heart sounds. His systolic pressure falls by 18 mmHg on inspiration, and echocardiography shows a pericardial effusion with collapse of the right ventricle in diastole. What is needed?

Intravenous furosemideUrgent drainage of the pericardial fluidA glyceryl trinitrate infusionIbuprofen and colchicine, with echocardiography in a week

4A woman treated with mediastinal radiotherapy 15 years ago has ascites, ankle swelling, a JVP that rises on inspiration, a sharp early diastolic sound and a heart of normal size. What is the most likely diagnosis?

Constrictive pericarditisCardiac tamponadeDilated cardiomyopathyCirrhosis of the liver

5Which feature in a patient with acute pericarditis calls for admission and a search for a specific cause?

Pain that is worse lying flat and better sitting forwardPR depression on the ECGA pericardial friction rubA temperature above 38 °C