PERICARDITIS

Saturn: An awe inspiring photograph taken by the Cassini deep space probe, October 6 2004. The shadow of the giant planet is cast over a segment of its spectacular rings that lie behind the planet relative to the Sun, rendering them completely invisible against the

backdrop of the black and infinite abyss of space.

“I had discovered Saturn to be three bodied…When I first saw them they seemed almost to touch, and they remained so for almost two years without the least change. It was reasonable to believe them to be fixed….Hence I stopped observing Saturn for more than two years. But in the past few days I returned to it and found it to be solitary, without its customary supporting stars, and as perfectly round and sharply bounded as Jupiter. Now what can be said of this strange metamorphosis? That the two lesser stars have been consumed?...Has Saturn devoured his children? Or was it indeed an illusion and a fraud with which the lenses of my telescope deceived me for so long - and not only me, but many others who have observed it with me?...I need not say anything definite upon so

strange and unexpected an event, too unparalleled, and I am restrained by my own inadequacy and the fear of error”.

Galileo Galilei, Letters on Sunspots, 1613

The magisterial Stephen Jay Gould used the story of Galileo’s discovery of the rings of Saturn, to demonstrate that so called “empiric” observation, is often constrained within a social and cultural context. Galileo in 1610 was the first person in history to observe the planets through a telescope. When he came to Saturn he noticed a most peculiar thing. It appeared to be distorted or elongated at its equator. It was totally unlike the perfect spheres of the other planets. His telescope was very crude by later standards, so interpretation of what he was seeing was extremely difficult. He concluded that two small “stars” accompanied the planet on either side of it, “I have observed that the farthest planet is threefold”, he wrote.

His other astronomical discoveries included that fact that there were vastly more stars in the sky than previously imagined. The Milky Way in fact consisted of many thousands, perhaps even millions of stars. Yet further discoveries made by Galileo began to sit uneasily with the established Christian Church of the day. The Moon for instance consisted of mountains and valleys and was not a perfect sphere. The newly discovered moons of Jupiter, by their orbits about the planet, he concluded, would smash through any so called crystalline spheres that supposedly supported each of the planets. These spheres obviously did not exist! Here he was on dangerous ground. He had caught the eye of the Inquisition, even before his more famous championing of the Copernican view of the universe.

At this time Galileo was in the vanguard of the new “empiric” or scientific method of inquiry into the natural world. This movement lead by Bacon in England, Descartes in France, was represented by a semi-secretive society in Italy, where to question established dogma was heresy. This society was know as the “Lynxes”, so named because of the remarkable visual acuity these creatures were known to have. The empiric method of direct observation with conclusions drawn thereupon lay in direct conflict with the teaching of established classical and religious dogma which said that any observation had to be interpreted and explained in the light of the established dogma – not questioned. And to question was heresy, punishable by persecution, torture and ultimately death. Yet the new empiric method when found to be in conflict with “established learning” was embarrassingly difficult to deny, Galileo would simply shrug his shoulders and quip...“I have observed it, I have seen it with my own eyes” – how could Aristotle, even the Pope himself deny such evidence as this?

The mysterious “stars” of Saturn, gradually came to be accepted on the “empiric” evidence championed by the supremely self-assured personality of Galileo, a man quite happy to contradict the Pope himself. He rapidly became the hero of the new scientific movement. Imagine his shock, therefore when after a period of two years spent on other pursuits Galileo looked once more for the stars of Saturn and found they were gone! He was stunned, as were many of his colleagues and followers. The Church, no doubt was ecstatic! A shaken and uncharacteristically humble Galileo, wrote, “I need not say anything definite upon so strange and unexpected an event, too unparalleled, and I am

restrained by my own inadequacy and the fear of error”. Had Saturn devoured his children, he wondered. He began to doubt that he had even seen the “stars” at all.

But Galileo was an empiric observer of unsurpassed excellence, indeed he had seen the “stars of Saturn”, and eventually they would return to view, though just exactly what they were and just why they had disappeared, was not established until more than a decade after Galileo’s death. In 1656 the great Dutch astronomer Christiaan Huygens, with a vastly superior telescope than that possessed by Galileo was able to establish the true nature of the “stars of Saturn”. Saturn possessed a series of spectacular rings which completely encircled it. The exact orientation of the planet with respect to an observer on the Earth determined just how visible these rings were. They were infinitely thinner than they were wide, and so when viewed directly edge on they became virtually invisible and definitely so via the instruments Galileo, or anyone had, at their disposal in the early Seventeenth century.

As Gould points out, there was nothing wrong with the new “empiric” method, however all observation, even by the most skilled, is constrained to greater or lesser degrees, by conceptual boundaries dictated by the social and cultural influences of the day. Galileo did not just “see” Saturn, as Gould points out, he had to interpret an object in his lens by classifying an ambiguous shape within the structure of his “mental space” – and giant rings encircling planets “did not inhabit this interior world”. There was not the slightest concept in the early Seventeenth century of such a fantastic possibility, and so what was empirically observed was interpreted in the only logical way known at the time. Galileo always continued to insist that Saturn was flanked by two small stars…”I have resolved not to put anything round Saturn except what I had already observed and revealed – that is two small stars which touch it, one to the east and one to the west”. In 1630 Francesco Stelluci an original member of the Lynx Society, wrote: “Not merely of the exterior eyes, but also of the mind, so necessary for the contemplation of nature, as we have taught, and as we practice, in our quest to penetrate into the interior of things, to know the causes and operations of nature…just as the Lynx, with its superior vision not only sees what lies outside, but also notes what arises from inside”. In 2004 the most spectacular views of Saturn and its rings were taken by NASA’s Cassini probe. In some views the rings even this close were not seen, shadowed by the giant planet blocking the rays of the far distant Sun. Galileo, even Huygens, would have been dumbfounded by these images, also one suspects quite humbled by these crowning achievements of the empiric enquiry they championed.

By empiric enquiry and observation of ECG recordings we may make a diagnosis of pericarditis. We should remember the lessons of the history of the discovery of the rings of Saturn however, “It was reasonable to believe them to be fixed…” in fact it was not! The signs of pericarditis just as the rings of Saturn can change from moment to moment. A pericardial rub may be transient, ECG changes may evolve. An open mind must be kept. We can see, but we should also understand. Pericarditis involves a degree of myocarditis a potentially far more serious condition. A period of ongoing observation is wise, lest we miss the true nature of the problem. We must not be complacent of potential complications, again we must not only see, but also understand. As the ancient god Saturn devoured his own children, so may pericarditis, in the form of cardiac tamponade, devour our patient.

PERICARDITIS

Introduction

Pericarditis simply refers to inflammation of the pericardium. Most cases are viral or idiopathic, (but presumed to be viral) in the majority of cases.

The condition is relatively common.

Most commonly the condition is benign, but this will also relate to the underlying pathology causing the inflammation.

Occasionally severe secondary complications may arise, such as the development of a large pericardial effusion that may lead to cardiac tamponade, or the condition may become chronic, leading to chronic constrictive pericarditis.

Characteristic changes are seen on the ECG, however the diagnosis may on occasions be a purely clinical one. It is important to recognize that the pericardium is electrically neutral and so ECG changes actually reflect an underlying epimyocarditis, there is a peri-myocarditis, in other words.

A diagnosis of acute pericarditis should be reserved for patients with an audible pericardial friction rub (so may be a clinical diagnosis) or chest pain with typical electrocardiographic findings, most notably widespread ST-segment elevation. 2

Most patients with ECG changes should be admitted.

Physiology

The pericardium is a double-layered fibroserous sac that envelops the heart, covering the cardiac surface and proximal roots of the great vessels.

The two layers of the sac consist of an inner serous (visceral) layer and an outer (parietal) fibrous layer.

The two layers of the pericardial sac are normally 1-2 mm in thickness and are separated by the pericardial space that normally contains 15-50 mls of pericardial fluid.

Pathophysiology

Causes

Pericardial inflammation has a wide range of diverse etiologies.

1. Viral:

The vast majority of cases are idiopathic or viral in original. Many idiopathic cases are probably viral in origin.

Viruses include those also implicated in myocarditis:

● Coxsackie B, echoviruses, polioviruses, adenovirus, CMV, EBV, influenza A&B, varicella, and HIV

● Many others however have been implicated.

Other causes of pericarditis are uncommon, or rare:

2. Other infective agents:

● Bacterial, (including tuberculosis)

Bacterial pericarditis is a rare but life-threatening cause.

● Unusual organisms, Parasitic, (Entameba histolytica, Echinococcus, Toxoplasma) or fungal (candida) in the imunosuppressed.

3. Malignancy.

4. Auto-immune:

● Connective tissue diseases, eg SLE, rheumatoid arthritis, rheumatic fever.

● Dressler’s syndrome, (10-14 days post myocardial infarction)

5. Radiation therapy.

6. Trauma:

● Penetrating.

● Blunt.

● Post peri-cardiotomy syndrome.

7. Drug induced.

● A large number of drugs have been implicated, however this cause is rare.

8. Systemic disease:

● Uraemia.

● Myxoedema.

Complications

Most cases of viral pericarditis run a benign course.

A number of serious complications are possible however and include:

● The development of a large pericardial effusion, with the subsequent possibility of the development of cardiac tamponade

● The progression to a chronic form of pericarditis, with the subsequent development of a chronic constrictive pericarditis

● There is an associated degree of myocarditis in many cases.

Clinical features

A diagnosis of acute pericarditis should be reserved for patients with an audible pericardial friction rub (so may be a clinical diagnosis) or chest pain with typical electrocardiographic findings, most notably widespread ST-segment elevation. 2

Important points of history:

1. Chest pain:

● Chest pain is typically pleuritic in nature.

● The pain is usually retrosternal, sometimes with radiation to the back, neck or trapezius muscle ridges or uncommonly the arms.

Pericardial pain is typically:

● Worse lying supine.

● Better by sitting up and leaning forward.

2. Respiration:

● True dyspnoea is not a feature, unless there secondary complications, such as cardiac tamponade or chronic constrictive pericarditis. Dyspnea may also be due to the underlying disease process that is causing the pericarditis.

● Respiration however may be shallow due to pain, (and a patient may interpret this as shortness of breath).

3, Other symptoms may relate to the underlying disease process that is causing the pericarditis.

4. Check if the patient is on oral anticoagulants, caution is required as a pericardial bleeding may occur.

5. Check the patient’s comorbidities:

● Immunosuppressed patients will be at greater risk for lethal bacterial pericarditis.

Important points of examination:

1. Viral or idiopathic types may present with low-grade fever.

● A body temperature greater than 38°C is uncommon however and may indicate purulent pericarditis, much more serious condition.

These patients should undergo prompt echocardiography, and the physician should consider obtaining pericardial fluid for analysis. 2

2. Pericardial rub:

● A pericardial friction rub may be heard, (or may not be) caused by rubbing between parietal and visceral layers of the pericardium or between parietal pericardial layer and the lung pleura. A rub may therefore be heard despite the presence of a large effusion.

● It may have mono, bi, or triphasic components to it.

● It may be heard anywhere over the precordium, but is said to be best heard with the diaphragm over the lower left sternal edge, while the patient holds the breath and leans forward.

● It has a “scratching” or “velcro” quality.

● The rub can be transitory and migratory from hour to hour, even minute to minute.

● A pericardial friction rub should not be confused with a pleural rub; a pericardial rub is still audible when the breath is held. By contrast, a pleural rub is timed with the respiratory cycle.

3. Signs of a complicating cardiac tamponade should always be looked for.

Clinical course

Pericarditis can present in four temporal forms:

● Acute, (most episodes lasting 1-2 weeks). 2

● Recurrent, (in 15-30% of idiopathic cases) 2

● Subacute

● Chronic

Investigations

Blood tests

These cannot make a diagnosis of pericarditis, but may provide confirmatory evidence for it.

1. FBE

● WCC may elevated, if markedly so this may indicate bacterial infection. 2

2. ESR/ CRP

● Acute phase reactants may be elevated.

3. U&Es / glucose:

● Uremic renal failure is a cause of pericarditis.

4. Troponin I

● There may be mild elevation, due to associated myocarditis.

5. Others as clinical suspicion dictates eg (rheumatoid factor, anti-nuclear factor, HIV)

ECG

In the occasional “pure” case of pericarditis (ie, without significant associated epimyocarditis), the ECG will be normal.

A typical evolution of pericarditis changes is seen over 4 stages in about 50% of cases.

Stage 1(Hours to days)

● Diffuse concave upward ST elevation, (often described as “Mexican Hats”).

● PR segment depression, in all leads apart from AVR and V1 where elevation may be seen.

Stage 2

● The PR and ST segments normalize, which can lead to a transiently normal ECG.

Stage 3 (Days to weeks)

● T wave inversion occurs.

Stage 4

● Normalization of the ECG over about 3 months, however, in some cases the T wave changes may be permanent.

See also appendix 1 below, for ECG features which may help distinguish pericarditis, from myocardial infarction and benign early repolarization.

Above shows an ECG with widespread ST segment, (concave upwards) elevation typical of acute pericarditis.

Left: Inferior ECG limb leads showing P-R segment depression, characteristic of pericarditis. Note that the PR depression is relative to the isoelectric line, which is taken from the segment immediately following the end of the T wave.

CXR

● This is done to help rule out other conditions.

● A large heart may suggest the presence of a pericardial effusion.

Echocardiography

● Echocardiography may show supportive evidence (but not specifically diagnostic) of pericardial effusion or thickening of the pericardium.

● It is useful for helping to rule out alternative diagnoses, or secondary complications, (such as cardiac tamponade).

● A joint task force of the American College of Cardiology, the American Heart Association, and the American Society of Echocardiography recommends that echocardiography be performed in all patients with known or suspected pericardial disease. 2

Pericardiocentesis and Biopsy

This is not routine, but may be indicated in some cases, including:

● A serious underlying pathology is suspected, such as bacterial, tuberculous or neoplastic pericarditis.

● When cardiac tamponade is present.

● Chronic or recurrent cases, for diagnostic purposes.

Biochemistry, cytology, microscopy and culture, and PCR testing can be done on pericardial fluid. A biopsy sample of pericardial tissue can be examined histologically.

Management

1. Admission:

Traditionally there has been a philosophy of “trivializing” the condition of acute pericarditis, and managing patients with this condition as outpatients.

In most cases however it is probably more prudent to admit even the seemingly “well” patient for at least a short period of observation. 4, 5

There are good reasons for admission, including:

Diagnostic uncertainty:

● The diagnosis of acute pericarditis can be difficult to establish. ECG changes can be subtle.

More important conditions such as ACS or myocarditis need to be confidently excluded before discharging a patient home and this is not always achievable on initial assessment in the ED

Monitoring:

● It must be kept in mind that ECG changes reflect a degree of myocarditis. The greater the degree of myocarditis, the potentially more severe will be the illness. Few cases of “pure” pericarditis are diagnosed on the basis of a pericardial rub and a normal ECG, so most diagnosed cases will have some degree of myocarditis.

● Patients with significantly elevated troponin levels are at increased risk and admission is mandatory in these cases. Myocarditis is the diagnosis when the troponin is elevated, not pericarditis.

● Patients with arrhythmias must be admitted for ongoing monitoring.

● Patients with large degrees of ST elevation must be admitted for ongoing monitoring, the diagnosis again may be primarily one of myocarditis.

Period of observation:

● Admission will allow for a period of observation to ensure that cardiac tamponade or arrhythmias do not develop.

Further investigation:

● Further investigations, such as echocardiography, cardiac MRI, even coronary angiography can be undertaken, where the patient appears ill or diagnostic uncertainty remains.

Pain control:

● The pain of pericarditis can range from mild to severe. Severe pain is a perfectly legitimate reason for admission.

2. NSAIDS:

Pain will be the primary concern of any patient suffering from pericarditis

● Nonsteroidal anti-inflammatory drugs are the mainstay of analgesic treatment. 4

● With high-dose NSAIDs, gastrointestinal protection with a proton pump inhibitor or H2 antagonist should be also considered

3. Colchicine:

● This has been advocated in combination with NSAIDS, where NSAIDS alone have not been able to control symptoms. 1, 2

● It is also an option in those who are unable to tolerate NSAIDS

● Colchicine offers the best prophylaxis against recurrent episodes. 1

4. Steroids:

Corticosteroids should be reserved for:

● Connective tissue disorders 4

● Autoimmune diseases

● Uraemic pericarditis

● Refractory cases where NSAIDS are unable to control symptoms. .

Some concerns have been raised that the use of steroids increases the risk of recurrence. 2

5. Aspirin:

● Aspirin has been shown to be effective in Dressler’s syndrome 4

6. Treat the underlying cause

Treat the underlying cause where this can be identified:

● Antibiotics for bacterial pericarditis

● Dialysis for uremic pericarditis

● Discontinue causative drugs if identified.

7. Rest:

● Avoidance of strenuous exercise is important during the acute phase of illness, primarily because of associated myocarditis. 5

8. Pericardiectomy:

● Pericardiectomy remains the definitive treatment for cases of chronic constrictive pericarditis and provides symptomatic relief in most cases.

● It has also been advocated as a “last resort” treatment in recurrent cases; however this has not proven successful in these cases, possibly due to persisting epitopes in the epicardium. 1

Disposition

If a patient is to be discharged home, it must be certain that the diagnosis is uncomplicated viral or idiopathic pericarditis, and not something potentially more serious. Patient comorbidities and social circumstances must also be taken into account. Close follow-up must be organized.

Most should however be admitted in the first instance.

Those with mild symptoms only and without complications may be suitable for a Short Stay Observation Unit Admission.

Those with arrhythmias, elevated troponin levels, significantly elevated ST segments or with diagnostic uncertainty should be admitted to a coronary care unit.

Those with serious underlying pathology, such as suspected bacterial or uremic pericarditis or with suspected complications such as cardiac tamponade must be referred to ICU/HDU Follow-up

Longer term follow-up of patients with pericarditis is necessary to observe for

● Possible recurrent episodes

● Evolution of an underlying pathology, such as connective tissue or autoimmune disease

● The development of a dilated cardiomyopathy.

Appendix 1: Pericarditis vs Myocardial Infarction vs Benign Early Repolarization

Table of ECG characteristics which may help differentiate pericarditis from myocardial infarction and benign early repolarization.

ECG Feature Acute Pericarditis Myocardial Infarction BER

ST segment morphology

Concave upwards ST elevation

Convex upwards ST elevation

Concave upwards ST elevation

ST segment elevation Usually < 5 mm May be > 5 mm, more suspicious the greater the elevation

< 5 mm

ST segment changes distribution

Diffuse Anatomic Precordial only

Reciprocal changes No, mild depressions only in AVR, VI

Deep reciprocal changes opposite ST elevated segments

No

Q waves No (unless associated with infarction)

Yes No

PR segments PR-segment depressions (maybe elevated in AVR and V1)

No No

T wave inversion T-wave inversion after ST segments normalize

T waves may invert concurrently with elevation of ST segments

No

ST/T ratio > 0.25 N/A < 0.25

Usual pattern of evolution of changes

Days to weeks Minutes to days Stable over many years.

“Saturn devouring His Son”, Francisco Goya, oil on canvas, c. 1819-23, Museo del Prado, Madrid

Francisco Goya’s startling image of the Roman god of antiquity, Saturn, devouring his own children, demonstrates the metaphor that Galileo used when he wondered whether the planet had somehow devoured the two smaller “stars” he had observed. Interestingly some 21st century astronomers would agree with this. One theory holds that the rings of Saturn are actually the remains of a planet or moon that strayed too close to the immense gravitational pull of the planet. As it got closer it was literally devoured, and the rings are all that are left of it!

References:

1. Troughton R W et al. Pericarditis, Lancet vol 363 February 28, 2004, p.717-727.

2. Lange R. A, Hills D.L Acute Pericarditis. NEJM November 18, 2004; 351: 2195-202.

3. Hayes J, Kelly A.M. Pericardits, Myocarditis and Cardiac Tamponade in Textbook of Adult Emergency Medicine: Cameron et al 3rd ed 2009.

4. Pericarditis in Emergency Medicine Therapeutic Guidelines, 1st ed 2008.

5. The Task Force on the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology. Guidelines on the Diagnosis and Management of Pericardial Diseases. European Heart Journal (2004) 25, 587–610

Further reading:

Gould S.J “The Sharp Eyed Lynx, Outfoxed by Nature” in “The Lying Stones of Marrakech”, Jonathan Cape, London, 2000.

Dr J. HayesReviewed 21 September 2009.