Abbreviations and acronyms
ADA
adenosine deaminase
AMI
acute myocardial infarction
ANA
anti-nuclear antibody
bFGF
basic fibroblast growth factor
CK
creatine kinase
CMR
cardiac magnetic resonance
CMV
cytomegalovirus
CP
Child–Pugh
CRP
C-reactive protein
CT
computed tomography
EBV
Epstein–Barr virus
ECG
electrocardiogram
ESR
erythrocyte sedimentation rate
ESRD
end-stage renal disease
FDG
fluorodeoxyglucose
FMF
familial Mediterranean fever
GM-CSF
granulocyte-macrophage colony-stimulating factor
HHV
human herpesvirus
HIV
human immunodeficiency virus
HR
hazard ratio
IL
interleukin
IVIG
intravenous immunoglobulins
LCE
late contrast-enhanced
NSAIDs
non-steroidal anti-inflammatory drugs
OR
odds ratio
PAH
pulmonary arterial hypertension
PCIS
post-cardiac injury syndromes
PCR
polymerase chain reaction
PET
positron emission tomography
PPS
post-pericardiotomy syndrome
RCT
randomized controlled trial
spp.
species
SSFP
steady-state free-precession
STIR
short-tau inversion-recovery
TB
tuberculosis
TNF
tumour necrosis factor
TRAPS
tumour necrosis factor receptor-associated periodic syndrome
TSH
thyroid stimulating hormone
Tx
treatment
uIFN-γ
unstimulated interferon-gamma
VEGF
vascular endothelial growth factor
Preamble
Guidelines summarize and evaluate all available evidence on a particular issue at
the time of the writing process, with the aim of assisting health professionals in
selecting the best management strategies for an individual patient with a given condition,
taking into account the impact on outcome, as well as the risk–benefit ratio of particular
diagnostic or therapeutic means. Guidelines and recommendations should help health
professionals to make decisions in their daily practice. However, the final decisions
concerning an individual patient must be made by the responsible health professional(s)
in consultation with the patient and caregiver as appropriate.
A great number of Guidelines have been issued in recent years by the European Society
of Cardiology (ESC) as well as by other societies and organisations. Because of the
impact on clinical practice, quality criteria for the development of guidelines have
been established in order to make all decisions transparent to the user. The recommendations
for formulating and issuing ESC Guidelines can be found on the ESC Web Site (http://www.escardio.org/Guidelines-&-Education/Clinical-Practice-Guidelines/Guidelines-development/Writing-ESC-Guidelines).
ESC Guidelines represent the official position of the ESC on a given topic and are
regularly updated.
Members of this Task Force were selected by the ESC to represent professionals involved
with the medical care of patients with this pathology. Selected experts in the field
undertook a comprehensive review of the published evidence for management (including
diagnosis, treatment, prevention and rehabilitation) of a given condition according
to ESC Committee for Practice Guidelines (CPG) policy. A critical evaluation of diagnostic
and therapeutic procedures was performed, including assessment of the risk–benefit
ratio. Estimates of expected health outcomes for larger populations were included,
where data exist. The level of evidence and the strength of the recommendation of
particular management options were weighed and graded according to predefined scales,
as outlined in Tables 1
and
2
.
The experts of the writing and reviewing panels provided declarations of interest
forms for all relationships that might be perceived as real or potential sources of
conflicts of interest. These forms were compiled into one file and can be found on
the ESC website (http://www.escardio.org/guidelines). Any changes in declarations
of interest that arise during the writing period must be notified to the ESC and updated.
The Task Force received its entire financial support from the ESC without any involvement
from the healthcare industry.
The ESC CPG supervises and coordinates the preparation of new Guidelines produced
by task forces, expert groups or consensus panels. The Committee is also responsible
for the endorsement process of these Guidelines. The ESC Guidelines undergo extensive
review by the CPG and external experts. After appropriate revisions the Guidelines
are approved by all the experts involved in the Task Force. The finalized document
is approved by the CPG for publication in the European Heart Journal. The Guidelines
were developed after careful consideration of the scientific and medical knowledge
and the evidence available at the time of their dating.
The task of developing ESC Guidelines covers not only the integration of the most
recent research, but also the creation of educational tools and implementation programmes
for the recommendations. To implement all guidelines, condensed pocket guidelines
versions, summary slides, booklets with essential messages, summary cards for non-specialists,
and an electronic version for digital applications (smartphones, etc.) are produced.
These versions are abridged and thus, if needed, one should always refer to the full
text version, which is freely available on the ESC website. The National Societies
of the ESC are encouraged to endorse, translate and implement the ESC Guidelines.
Implementation programmes are needed because it has been shown that the outcome of
disease may be favourably influenced by the thorough application of clinical recommendations.
Surveys and registries are needed to verify that real-life daily practice is in keeping
with what is recommended in the guidelines, thus completing the loop between clinical
research, writing of guidelines, disseminating them and implementing them into clinical
practice.
Health professionals are encouraged to take the ESC Guidelines fully into account
when exercising their clinical judgment, as well as in the determination and the implementation
of preventive, diagnostic or therapeutic medical strategies. However, the ESC Guidelines
do not override in any way whatsoever the individual responsibility of health professionals
to make appropriate and accurate decisions in consideration of each patient's health
condition and in consultation with that patient and the patient's caregiver where
appropriate and/or necessary. It is also the health professional's responsibility
to verify the rules and regulations applicable to drugs and devices at the time of
prescription.
Table 1
Classes of recommendations
Table 2
Levels of evidence
1.
Introduction
The pericardium (from the Greek περί, ‘around’ and κάρδιον, ‘heart’) is a double-walled
sac containing the heart and the roots of the great vessels. The pericardial sac has
two layers, a serous visceral layer (also known as epicardium when it comes into contact
with the myocardium) and a fibrous parietal layer. It encloses the pericardial cavity,
which contains pericardial fluid. The pericardium fixes the heart to the mediastinum,
gives protection against infection and provides lubrication for the heart.
Pericardial diseases may be either isolated disease or part of a systemic disease.
1–5
The main pericardial syndromes that are encountered in clinical practice include pericarditis
(acute, subacute, chronic and recurrent), pericardial effusion, cardiac tamponade,
constrictive pericarditis and pericardial masses.
1,4,5
All medical therapies for pericardial diseases are off-label, since no drug has been
registered until now for a specific pericardial indication.
1.1
What is new in pericardial diseases?
Pericardial diseases are relatively common in clinical practice and new data have
been published since the publication of the 2004 ESC Guidelines on pericardial diseases.
1
New diagnostic strategies have been proposed for the triage of patients with pericarditis
and pericardial effusion and allow the selection of high-risk patients to be admitted
as well as when and how additional diagnostic investigations are to be performed.
4–9
Moreover, specific diagnostic criteria have been proposed for acute and recurrent
pericarditis in clinical practice.
2,4–15
Multimodality imaging for pericardial diseases has become an essential approach for
a modern and comprehensive diagnostic evaluation. Both the American Society of Echocardiography
and the European Association of Cardiovascular Imaging have provided recommendation
documents in recent years.
2,3
The aetiology and pathophysiology of pericardial diseases remain to be better characterized,
but new data supporting the immune-mediated pathogenesis of recurrences and new forms
related to autoinflammatory diseases have been documented, especially in paediatric
patients.
4,6
The first epidemiological data have become available.
7,16
Age and gender issues are now more evident and clear, including specific recommendations
for patients during pregnancy.
17–27
Major advances have occurred in therapy with the first multicentre randomized clinical
trials.
10,11,13–15
Colchicine has been demonstrated as a first-line drug to be added to conventional
anti-inflammatory therapies in patients with a first episode of pericarditis or recurrences
in order to improve the response to therapy, increase remission rates and reduce recurrences.
10,11,13–15
Specific therapeutic dosing without a loading dose and weight-adjusted doses have
been proposed to improve patient compliance.
11,15
New therapeutic choices have become available for refractory recurrent pericarditis,
including alternative immunosuppressive therapies (e.g. azathioprine), intravenous
immunoglobulins (IVIGs) and interleukin-1 (IL-1) antagonists (e.g. anakinra).
20–23,28–32
Pericardiectomy has been demonstrated as a possible valuable alternative to additional
medical therapies in patients with refractory recurrent pericarditis.
33
The first large prospective and retrospective studies (>100 patients) have investigated
the prognosis and complication risk in patients with acute and recurrent pericarditis.
7,9,34–38
Imaging techniques for the detection of pericardial inflammation [e.g. cardiac magnetic
resonance (CMR)] may identify forms of initial reversible constrictive pericarditis,
allowing a trial of medical anti-inflammatory therapy that may reduce the need for
surgery.
2,39–41
In conclusion, significant new data have become available since 2004, and a new version
of guidelines has become mandatory for clinical practice. Nevertheless, in the field
of pericardial diseases there are a limited number of randomized controlled trials
(RCTs). Therefore the number of class I level A indications are limited.
2.
Epidemiology, aetiology and classification of pericardial diseases
2.1
Epidemiology
Despite the relative high frequency of pericardial diseases, there are few epidemiological
data, especially from primary care. Pericarditis is the most common disease of the
pericardium encountered in clinical practice. The incidence of acute pericarditis
has been reported as 27.7 cases per 100,000 population per year in an Italian urban
area.
7
Pericarditis is responsible for 0.1% of all hospital admissions and 5% of emergency
room admissions for chest pain.
4,5,42
Data collected from a Finnish national registry (2000–9) showed a standardized incidence
rate of hospitalizations for acute pericarditis of 3.32 per 100,000 person-years.
16
These data were limited to hospitalized patients and therefore may account for only
a minority of cases, as many patients with pericarditis are commonly not admitted
to hospital.
8,9,42,43
Men ages 16–65 years were at higher risk for pericarditis (relative risk 2.02) than
women in the general admitted population, with the highest risk difference among young
adults compared with the overall population. Acute pericarditis caused 0.20% of all
cardiovascular admissions. The proportion of caused admissions declined by an estimated
51% per 10-year increase in age. The in-hospital mortality rate for acute pericarditis
was 1.1% and was increased with age and severe co-infections (pneumonia or septicaemia).
16
However, this is a study based on hospital admissions only. Recurrences affect about
30% of patients within 18 months after a first episode of acute pericarditis.
10,11
2.2
Aetiology
A simple aetiological classification for pericardial diseases is to consider infectious
and non-infectious causes (Table 3
).
4,6,12,44
The aetiology is varied and depends on the epidemiological background, patient population
and clinical setting. In developed countries, viruses are usually the most common
aetiological agents of pericarditis,
6
whereas tuberculosis (TB) is the most frequent cause of pericardial diseases in the
world and developing countries, where TB is endemic. In this setting, TB is often
associated with human immunodeficiency virus (HIV) infection, especially in sub-Saharan
Africa.
44
Table 3
Aetiology of pericardial diseases. The pericardium may be affected by all categories
of diseases, including infectious, autoimmune, neoplastic, iatrogenic, traumatic,
and metabolic
CMV = cytomegalovirus; EBV = Epstein-Barr virus; GM-CSF = granulocyte-macrophage colonystimulating
factor; HHV = human herpesvirus; spp = species; TNF = tumor necrosis factor.
3.
Pericardial syndromes
Pericardial syndromes include different clinical presentations of pericardial diseases
with distinctive signs and symptoms that can be grouped in specific ‘syndromes’. The
classical pericardial syndromes include pericarditis, pericardial effusion, cardiac
tamponade and constrictive pericarditis. Pericardial effusion and cardiac tamponade
may occur without pericarditis and will be considered in separate chapters. Specific
considerations apply to cases with pericarditis and concomitant myocardial inflammatory
involvement, usually referred to in the literature as ‘myopericarditis’.
3.1
Acute pericarditis
Acute pericarditis is an inflammatory pericardial syndrome with or without pericardial
effusion.
1–11,42
The clinical diagnosis can be made with two of the following criteria (Table 4
):
2,4–15
(i) chest pain (>85–90% of cases)—typically sharp and pleuritic, improved by sitting
up and leaning forward; (ii) pericardial friction rub (≤33% of cases)—a superficial
scratchy or squeaking sound best heard with the diaphragm of the stethoscope over
the left sternal border; (iii) electrocardiogram (ECG) changes (up to 60% of cases)—with
new widespread ST elevation or PR depression in the acute phase (
Web Figure 1
); and (iv) pericardial effusion (up to 60% of cases, generally mild) (
Web Figure 2
). Additional signs and symptoms may be present according to the underlying aetiology
or systemic disease (i.e. signs and symptoms of systemic infection such as fever and
leucocytosis, or systemic inflammatory disease or cancer).
45
Table 4
Definitions and diagnostic criteria for pericarditis (see text for explanation)
CMR = cardiac magnetic resonance; CT = computed tomography;
ECG = electrocardiogram.
aUsually within 18–24 months but a precise upper limit of time has not been established.
Widespread ST-segment elevation has been reported as a typical hallmark sign of acute
pericarditis (
Web Figure 1
). However, changes in the ECG imply inflammation of the epicardium, since the parietal
pericardium itself is electrically inert.
5–7,34
Typical ECG changes have been reported in up to 60% of cases.
10,11
The temporal evolution of ECG changes with acute pericarditis is highly variable from
one patient to another and is affected by therapy. Major differential diagnoses include
acute coronary syndromes with ST-segment elevation and early repolarization.
6,12,46
Elevation of markers of inflammation [i.e. C-reactive protein (CRP) and erythrocyte
sedimentation rate (ESR), as well as elevation of the white blood cell count] is a
common and supportive finding in patients with acute pericarditis and may be helpful
for monitoring the activity of the disease and efficacy of therapy.
2,47
Patients with concomitant myocarditis may present with an elevation of markers of
myocardial injury [i.e. creatine kinase (CK), troponin].
7,34
A chest X-ray is generally normal in patients with acute pericarditis since an increased
cardiothoracic ratio only occurs with pericardial effusions exceeding 300 ml.
48
In the case of pleuropulmonary diseases, signs of pleuropericardial involvement may
be found in patients with pericarditis.
2,3
Recommendations for diagnosis of acute pericarditis
CK = creatine kinase; CRP = C-reactive protein; ECG = electrocardiogram.
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
3.1.1
Clinical management and therapy
It is not mandatory to search for the aetiology in all patients, especially in countries
with a low prevalence of TB, because of the relatively benign course associated with
the common causes of pericarditis and the relatively low yield of diagnostic investigations.
6,8,12,49
Specific final identifiable causes (non-viral–non-idiopathic) as well as high-risk
features in the context of acute pericarditis have been identified as being associated
with an increased risk of complications during follow-up (tamponade, recurrences and
constriction).
9,12,43,50
The major risk factors associated with poor prognosis after multivariate analysis
include high fever [>38°C (>100.4°F)], subacute course (symptoms over several days
without a clear-cut acute onset), evidence of large pericardial effusion (i.e. diastolic
echo-free space >20 mm), cardiac tamponade and failure to respond within 7 days to
non-steroidal anti-inflammatory drugs (NSAIDs).
9,43,50
Other risk factors should also be considered (i.e. ‘minor risk factors’); these are
based on expert opinion and literature review, including pericarditis associated with
myocarditis (myopericarditis), immunodepression, trauma and oral anticoagulant therapy.
On this basis a triage for acute pericarditis is proposed (Figure 1
,
Web Table 6
).
5,6,43
Any clinical presentation that may suggest an underlying aetiology (e.g. a systemic
inflammatory disease) or with at least one predictor of poor prognosis (major or minor
risk factors) warrants hospital admission and an aetiology search.
9,43,49–51
On the other hand, patients without these features can be managed as outpatients with
empiric anti-inflammatories and short-term follow-up after 1 week to assess the response
to treatment.
9
Recommendations for the management of acute pericarditis
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
dSee Figure 1
(both major and minor predictors of poor prognosis).
In patients identified with a cause other than viral infection, specific therapy appropriate
to the underlying disorder is indicated
49,51
and the epidemiological background (high vs. low prevalence of TB) should be considered.
8,12,52
The first non-pharmacological recommendation is to restrict physical activity beyond
ordinary sedentary life until resolution of symptoms and normalization of CRP for
patients not involved in competitive sports.
53
Athletes are recommended to return to competitive sports only after symptoms have
resolved and diagnostic tests (i.e. CRP, ECG and echocardiogram) have been normalized.
53,54
A minimal restriction of 3 months (after the initial onset of the attack) has been
arbitrarily defined according to expert consensus.
54
We suggest applying this restriction only to athletes, while a shorter period (until
remission) may be suitable for non-athletes. Aspirin or NSAIDs are mainstays of therapy
for acute pericarditis.
5,6,55,56
Different anti-inflammatory drugs have been proposed (Table 5
).
Table 5
Commonly prescribed anti-inflammatory therapy for acute pericarditis
b.i.d. = twice daily; CRP = C-reactive protein; NSAIDs = non-steroidal anti-inflammatory
drugs; Tx = treatment.
aTapering should be considered for aspirin and NSAIDs.
bTx duration is symptoms and CRP guided but generally 1–2 weeks for uncomplicated
cases. Gastroprotection should be provided. Colchicine is added on top of aspirin
or ibuprofen.
The choice of drug should be based on the history of the patient (contraindications,
previous efficacy or side effects), the presence of concomitant diseases (favouring
aspirin over other NSAIDs when aspirin is already needed as antiplatelet treatment)
and physician expertise.
56
Figure 1
Proposed triage of pericarditis.
Colchicine is recommended at low, weight-adjusted doses to improve the response to
medical therapy and prevent recurrences.
10,11,57–59
Tapering of colchicine is not mandatory but may be considered to prevent persistence
of symptoms and recurrence.
5,6,56
Corticosteroids should be considered as a second option in patients with contraindications
and failure of aspirin or NSAIDs because of the risk of favouring the chronic evolution
of the disease and promoting drug dependence; in this case they are used with colchicine.
If used, low to moderate doses (i.e. prednisone 0.2–0.5 mg/kg/day or equivalent) should
be recommended instead of high doses (i.e. prednisone 1.0 mg/kg/day or equivalent).
35
The initial dose should be maintained until resolution of symptoms and normalization
of CRP, then tapering should be considered.
5,6,35,47,56
Recommendations for the treatment of acute pericarditis
CRP = C-reactive protein; ECG = electrocardiogram; NSAIDs = non-steroidal anti-inflammatory
drugs.
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
dAdded to colchicine.
3.1.2
Prognosis
Most patients with acute pericarditis (generally those with presumed viral or idiopathic
pericarditis) have a good long-term prognosis.
36
Cardiac tamponade rarely occurs in patients with acute idiopathic pericarditis, and
is more common in patients with a specific underlying aetiology such as malignancy,
TB or purulent pericarditis. Constrictive pericarditis may occur in <1% of patients
with acute idiopathic pericarditis, and is also more common in patients with a specific
aetiology. The risk of developing constriction can be classified as low (<1%) for
idiopathic and presumed viral pericarditis; intermediate (2–5%) for autoimmune, immune-mediated
and neoplastic aetiologies; and high (20–30%) for bacterial aetiologies, especially
with TB and purulent pericarditis.
36
Approximately 15–30% of patients with idiopathic acute pericarditis who are not treated
with colchicine will develop either recurrent or incessant disease, while colchicine
may halve the recurrence rate.
10,11,13–15
3.2
Incessant and chronic pericarditis
The term ‘incessant’ has been adopted for cases with persistent symptoms without a
clear-cut remission after the acute episode. The term ‘chronic’ generally refers—especially
for pericardial effusions—to disease processes lasting >3 months.
48
The Task Force suggests that the term ‘acute’ should be adopted for new-onset pericarditis,
‘incessant’ for pericarditis with symptoms persisting for >4–6 weeks (that is generally
the approximate length of conventional anti-inflammatory therapy and its tapering),
11,60
and ‘chronic’ for pericarditis lasting >3 months.
3.3
Recurrent pericarditis
Recurrent pericarditis is diagnosed with a documented first episode of acute pericarditis,
a symptom-free interval of 4–6 weeks or longer and evidence of subsequent recurrence
of pericarditis (Table 4
).
11,13–15
Diagnosis of recurrence is established according to the same criteria as those used
for acute pericarditis. CRP,
2,47
computed tomography (CT) and/or CMR may provide confirmatory findings to support the
diagnosis in atypical or doubtful cases showing pericardial inflammation through evidence
of oedema and contrast enhancement of the pericardium.
2,39
The recurrence rate after an initial episode of pericarditis ranges from 15 to 30%,
10,11
and may increase to 50% after a first recurrence in patients not treated with colchicine,
13–15
particularly if treated with corticosteroids.
In developed countries, the aetiology is often not identified in most immunocompetent
patients, and it is generally presumed to be immune-mediated.
60–62
A common cause of recurrence is inadequate treatment of the first episode of pericarditis.
In up to 20% of cases, when additional virological studies have been conducted on
pericardial fluid and tissue, a viral aetiology is detected.
63
3.3.1
Therapy
Recurrent pericarditis therapy should be targeted at the underlying aetiology in patients
with an identified cause. Aspirin or NSAIDs remain the mainstay of therapy (Table
6
, Web Box,
Web Table 1A). Colchicine is recommended on top of standard anti-inflammatory therapy,
without a loading dose and using weight-adjusted doses (i.e. 0.5 mg once daily if
body weight is <70 kg or 0.5 mg twice daily if it is ≥70 kg, for ≥6 months) (Table
6
,
Web Table 1B) in order to improve the response to medical therapy, improve remission
rates and prevent recurrences.
13–15,58,59
Table 6
Commonly prescribed anti-inflammatory therapies for recurrent pericarditis (for further
details see Web Tables 1A and 1B)
Tx = treatment.
aTapering should be considered for aspirin and NSAIDs.
bLonger tapering times for more difficult, resistant cases may be considered.
In cases of incomplete response to aspirin/NSAIDs and colchicine, corticosteroids
may be used, but they should be added at low to moderate doses to aspirin/NSAIDs and
colchicine as triple therapy, not replace these drugs, in order to achieve better
control of symptoms. Corticosteroids at low to moderate doses (i.e. prednisone 0.2–0.5
mg/kg/day) should be avoided if infections, particularly bacterial and TB, cannot
be excluded and should be restricted to patients with specific indications (i.e. systemic
inflammatory diseases, post-pericardiotomy syndromes, pregnancy) or NSAID contraindications
(true allergy, recent peptic ulcer or gastrointestinal bleeding, oral anticoagulant
therapy when the bleeding risk is considered high or unacceptable) or intolerance
or persistent disease despite appropriate doses.
58
Although corticosteroids provide rapid control of symptoms, they favour chronicity,
more recurrences and side effects.
35,55,61
If corticosteroids are used, their tapering should be particularly slow. A critical
threshold for recurrences is a 10–15 mg/day dose of prednisone or equivalent. At this
threshold, very slow decrements as small as 1.0–2.5 mg at intervals of 2–6 weeks are
useful. In cases of recurrence, every effort should be made not to increase the dose
or to reinstate corticosteroids (Tables 6
and
7
).
5,6,35,61
After obtaining a complete response, tapering should be done with a single class of
drug at a time before colchicine is gradually discontinued (over several months in
the most difficult cases). Recurrences are possible after discontinuation of each
drug. Each tapering should be attempted only if symptoms are absent and CRP is normal.
5,6,47,56
The Task Force does not recommend influenza vaccine as a preventive measure for pericarditis
in patients with recurrent pericarditis, since the influenza virus is not a usual
cause of pericarditis. The influenza vaccine should be administered according to specific
indications beyond pericarditis; moreover, recurrences are generally immune mediated,
and inappropriate or unwanted stimulation of the immune system may trigger or worsen
an episode of pericarditis.
An alternative effective approach to minimize systemic side effects related to corticosteroids
may be intrapericardial administration of non-absorbable corticosteroids,
64,65
but this technique requires further investigation. For those patients who require
unacceptably high long-term doses of corticosteroids (e.g. prednisone 15–25 mg/day)
or who do not respond to anti-inflammatory therapies, several drugs have been used,
including azathioprine,
28
IVIG (immunomodulatory but also anti-viral)
29,30
and anakinra, a recombinant IL-1β receptor antagonist,
31,32
but strong evidence-based data are lacking (
Web Table 2
). Other immunosuppressive drugs [i.e. cyclophosphamide, cyclosporine, methotrexate,
hydroxychloroquine, anti-tumour necrosis factor (TNF) agents] have been only anecdotally
reported. Less toxic agents might be preferred, and eventually combined, with the
therapy being tailored to the individual patient and physician experience (Figure
2
). Azathioprine is mainly a slow-acting corticosteroid-sparing agent, useful to control
the disease for a long-term follow-up, while anakinra and IVIG are effective during
the acute phase, though recurrences may occur after discontinuation.
29–32
Drugs such as IVIG, anakinra and azathioprine may be considered in cases of proven
infection-negative, corticosteroid-dependent, recurrent pericarditis not responsive
to colchicine after careful assessment of the costs, risks and eventually consultation
by multidisciplinary experts, including immunologists and/or rheumatologists, in the
absence of a specific expertise. It is also mandatory to educate the patient and his/her
caregivers about the clinical risks related to immunomodulatory/immunosuppressive
drugs and the safety measures to adopt during the treatment. As a last resort, pericardiectomy
may be considered, but only after a thorough trial of unsuccessful medical therapy,
and with referral of the patient to a centre with specific expertise in this surgery.
33
The physical activity restrictions in acute pericarditis apply also to recurrences.
53,54
Recommendations for the management of recurrent pericarditis
CRP = C-reactive protein; ECG = electrocardiogram; IVIG = intravenous immunoglobulin;
NSAIDs = non-steroidal anti-inflammatory drugs.
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
3.3.2
Prognosis
Severe complications are uncommon in idiopathic recurrent pericarditis.
37,60,61
Cardiac tamponade is rare and generally occurs at the beginning of the disease. Constrictive
pericarditis has never been reported in these patients, despite numerous recurrences,
and the overall risk is lower than that recorded after a first episode of acute pericarditis
(<1%).
36,37,61
Thus it is important to reassure patients about their prognosis, explaining the nature
of the disease and its likely course. The complication rates are related to the aetiology
and not to the number of recurrences. Drug treatment should take into account this
favourable outcome to avoid more toxic agents. However, quality of life can be severely
affected in patients with repeated recurrences, subacute or incessant pericarditis
and glucocorticoid dependence.
Figure 2
Therapeutic algorithm for acute and recurrent pericarditis (see text for explanation).
3.4
Pericarditis associated with myocardial involvement (myopericarditis)
Pericarditis and myocarditis share common aetiologies, and overlapping forms may be
encountered in clinical practice.
34,66
Pericarditis with known or clinically suspected concomitant myocardial involvement
should be referred to as ‘myopericarditis’, while predominant myocarditis with pericardial
involvement should be referred to as ‘perimyocarditis’, according to Task Force consensus.
The classical presentation is chest pain associated with other signs of pericarditis
(pericardial rubs, ST-segment elevation and pericardial effusion) plus the elevation
of markers of myocardial damage (i.e. troponins). Limited clinical data on the causes
of myopericarditis suggest that viral infections are among the most common causes
in developed countries, while other infectious causes are more common in developing
countries (especially TB). Cardiotropic viruses can cause pericardial and myocardial
inflammation via direct cytolytic or cytotoxic effects and/or subsequent immune-mediated
mechanisms. Such mechanisms are especially involved in cases associated with connective
tissue diseases, inflammatory bowel diseases and radiation-induced, drug-induced or
vaccinia-associated myopericardial involvement. Many cases of myopericarditis are
subclinical. In other patients, cardiac symptoms and signs are masked by pronounced
systemic manifestations of infection or inflammation.
66
In many cases, myopericarditis manifestations are preceded by or are sometimes concomitant
with an acute respiratory illness (especially acute tonsillitis, pneumonia) or gastroenteritis.
The increased sensitivity of troponin assays and contemporary widespread use of troponins
has greatly increased the reported number of cases.
7,34,66–68
3.4.1
Definition and diagnosis
The diagnosis of predominant pericarditis with myocardial involvement, or ‘myopericarditis’,
can be clinically established if patients with definite criteria for acute pericarditis
show elevated biomarkers of myocardial injury (troponin I or T, CK-MB fraction) without
newly developed focal or diffuse impairment of left ventricular function in echocardiography
or CMR.
34
The term myopericarditis indicates a primarily pericarditic syndrome with minor myocardial
involvement, which describes the majority of combined pericarditis and myocarditis
cases encountered in clinical practice.
7,9,34,68
On the other hand, evidence of new-onset focal or diffuse reduction of left ventricular
function in patients with elevated myocardial biomarkers and clinical criteria for
acute pericarditis suggests predominant myocarditis with pericardial involvement (‘perimyocarditis’).
34,66
Definite confirmation of the presence of myocarditis will require endomyocardial biopsy
according to the Myocardial and Pericardial Diseases Working Group position statement.
69
However, the benign prognosis of patients with suspected concomitant myocardial involvement
in predominant pericarditis (myopericarditis), with absent or mild left ventricular
dysfunction, and no symptoms of heart failure does not clinically require endomyocardial
biopsy.
6,34,66–68,70,71
In cases of pericarditis with suspected associated myocarditis, coronary angiography
(according to clinical presentation and risk factor assessment) is recommended in
order to rule out acute coronary syndromes. CMR is recommended for the confirmation
of myocardial involvement and to rule out ischaemic myocardial necrosis in the absence
of significant coronary disease; this has clinical and therapeutic implications.
34,66
3.4.2
Management
Hospitalization is recommended for diagnosis and monitoring of patients with myocardial
involvement and differential diagnosis, especially with acute coronary syndromes.
In the setting of myopericarditis, management is similar to that recommended for pericarditis.
Empirical anti-inflammatory therapies (i.e. aspirin 1500–3000 mg/day) or NSAIDs (ibuprofen
1200–2400 mg/day or indomethacin 75–150 mg/day) are usually prescribed to control
chest pain, while corticosteroids are prescribed as a second choice in cases of contraindication,
intolerance or failure of aspirin/NSAIDs.
66
In the setting of myopericarditis, some authors recommend reducing dosages, as compared
with pure pericarditis, because in animal models of myocarditis, NSAIDs have been
shown to be non-efficacious and may enhance inflammation, increasing mortality.
69,70,72,73
However, the application of these findings from animal models to humans may be questionable.
66
In addition, there are insufficient data to recommend the use of colchicine, which
is a well-established adjunctive treatment for acute and recurrent pericarditis.
58
Despite the lack of specific therapies for most cases, several non-specific recommendations
are important. Rest and avoidance of physical activity beyond normal sedentary activities
is recommended in all patients with myopericarditis.
53,54,66
Sudden cardiac death cases have been reported in military personnel after strenuous
exertion and also in male athletes without prodromic symptoms [football (soccer) players,
swimming].
53,54,66
While in isolated pericarditis, return to exercise is permissible when there is no
further evidence of active disease in non-athletes, or after 3 months in athletes,
the presence or suspicion of myocardial involvement leads to contraindication of physical
exercise for at least 6 months from the onset of the illness according to expert opinion
and previous recommendations for participation in competitive sports.
53,54,66
3.4.3
Prognosis
Myocardial involvement in pericarditis has a good prognosis, and several observational
series have demonstrated no evolution to heart failure or mortality in patients with
myopericarditis.
34,66–68,70,71
Recommendations for the diagnosis and management of pericarditis associated with myocarditis
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
3.5
Pericardial effusion
The normal pericardial sac contains 10–50 ml of pericardial fluid as a plasma ultrafiltrate
that acts as a lubricant between the pericardial layers. Any pathological process
usually causes an inflammation with the possibility of increased production of pericardial
fluid (exudate). An alternative mechanism of accumulation of pericardial fluid may
be decreased reabsorption due to a general increase in systemic venous pressure as
a result of congestive heart failure or pulmonary hypertension (transudate).
48
Pericardial effusion may be classified according to its onset (acute or subacute vs.
chronic when lasting >3 months), distribution (circumferential or loculated), haemodynamic
impact (none, cardiac tamponade, effusive-constrictive), composition (exudate, transudate,
blood, rarely air, or gas from bacterial infections) and, in particular, by its size
(Table 8
) based on a simple semiquantitative echocardiographic assessment as mild (<10 mm),
moderate (10–20 mm) or large (>20 mm) (
Web Figure 2
).
48
This semiquantitative assessment has also proven to be useful in estimating the risk
of specific aetiology and complications during follow-up in the setting of pericarditis.
9,48,51
In the last 20 years, five major surveys have been published on the characteristics
of moderate to large pericardial effusions (
Web Table 3
).
74–78
Table 7
Tapering of corticosteroids
35
(dosage information is provided for prednisone)
aAvoid higher doses except for special cases, and only for a few days, with rapid
tapering to 25 mg/day. Prednisone 25 mg are equivalent to methylprednisolone 20 mg.
bEvery decrease in prednisone dose should be done only if the patient is asymptomatic
and C-reactive protein is normal, particularly for doses <25 mg/day.
Calcium intake (supplement plus oral intake) 1,200–1,500 mg/day and vitamin D supplementation
800–1000 IU/day should be offered to all patients receiving glucocorticoids. Moreover,
bisphosphonates are recommended to prevent bone loss in all men ≥50 years and postmenopausal
women in whom long-term treatment with glucocorticoids is initiated at a dose ≥5.0–7.5
mg/day of prednisone or equivalent.
Table 8
Classification of pericardial effusion
A significant proportion of patients with pericardial effusion are asymptomatic and
pericardial effusion constitutes an incidental and unexpected finding on X-ray or
echocardiogram performed for other reasons. According to these series, many cases
remain idiopathic in developed countries (up to 50%), while other common causes include
cancer (10–25%), infections (15–30%), iatrogenic causes (15–20%) and connective tissue
diseases (5–15%), whereas TB is the dominant cause in developing countries (>60%),
where TB is endemic.
52,79
In the setting of pericarditis with pericardial effusion, the prevalence of malignant
or infectious aetiologies ranges from 15 to 50% depending on the published series.
6,9
3.5.1
Clinical presentation and diagnosis
The clinical presentation of pericardial effusion varies according to the speed of
pericardial fluid accumulation. If pericardial fluid is rapidly accumulating, such
as after wounds or iatrogenic perforations, the evolution is dramatic and even small
amounts of blood may cause an increase in intrapericardial pressure within minutes
and overt cardiac tamponade. On the other hand, a slow accumulation of pericardial
fluid allows the collection of a large effusion in days to weeks before a significant
increase in pericardial pressure causes symptoms and signs (
Web Figure 3
).
48,80,81
Classic symptoms include dyspnoea on exertion progressing to orthopnoea, chest pain
and/or fullness. Additional occasional symptoms due to local compression may include
nausea (diaphragm), dysphagia (oesophagus), hoarseness (recurrent laryngeal nerve)
and hiccups (phrenic nerve). Non-specific symptoms include cough, weakness, fatigue,
anorexia and palpitations, and reflect the compressive effect of the pericardial fluid
on contiguous anatomic structures or reduced blood pressure and secondary sinus tachycardia.
82–84
Fever is a non-specific sign that may be associated with pericarditis, either infectious
or immune mediated (i.e. systemic inflammatory diseases).
45
Physical examination may be absolutely normal in patients without haemodynamic compromise.
When tamponade develops, classic signs include neck vein distension with elevated
jugular venous pressure at bedside examination, pulsus paradoxus and diminished heart
sounds on cardiac auscultation in cases of moderate to large effusions.
82–84
Pericardial friction rubs are rarely heard; they can usually be detected in patients
with concomitant pericarditis.
8
The diagnosis of pericardial effusion is generally performed by echocardiography,
which also enables semiquantitative assessment of the pericardial effusion size and
its haemodynamic effects. Although echocardiography remains the primary diagnostic
tool for the study of pericardial diseases because of its widespread availability,
portability and limited costs, CT and CMR provide a larger field of view, allowing
the detection of loculated pericardial effusion and pericardial thickening and masses,
as well as associated chest abnormalities.
2,3,84
Recommendations for the diagnosis of pericardial effusion
CMR = cardiac magnetic resonance; CRP = C-reactive protein; CT = computed tomography.
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
3.5.2
Triage and management
When a pericardial effusion is detected, the first step is to assess its size, haemodynamic
importance (especially the presence of cardiac tamponade) and possible associated
diseases (either cardiovascular or systemic diseases). Pericardial effusion is often
associated with known or unknown (e.g. hypothyroidism) medical conditions (up to 60%
of cases).
48,75,82
If inflammatory signs are present, the clinical management should be that of pericarditis.
Cardiac tamponade without inflammatory signs is associated with a higher risk of a
neoplastic aetiology (likelihood ratio 2.9), whereas a severe effusion without cardiac
tamponade and inflammatory signs is usually associated with a chronic idiopathic aetiology
(likelihood ratio 20).
75
A practical routine evaluation for triage of pericardial effusion is presented in
Figure 3
.
48,82
Recommendations for the initial management of pericardial effusion
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
dSimilar risk criteria as for pericarditis (see Figure 1
).
In chronic effusion with no definite aetiology, there are no data on non-steroidal
anti-inflammatory drugs (NSAIDs), colchicine and corticosteroids. If markers of inflammation
are elevated, a trial of NSAIDs and/or colchicine and/or low-dose corticosteroids
may be tried.
3.5.3
Therapy
Therapy of pericardial effusion should be targeted at the aetiology as much as possible.
In about 60% of cases, the effusion is associated with a known disease and the essential
treatment is that of the underlying disease.
48,75,82
When pericardial effusion is associated with pericarditis, management should follow
that of pericarditis. When a pericardial effusion becomes symptomatic without evidence
of inflammation or when empiric anti-inflammatory drugs are not successful, drainage
of the effusion should be considered. Pericardiocentesis with prolonged pericardial
drainage of up to 30 ml/24 h may be considered in order to promote adherence of pericardial
layers and prevent further accumulation of fluid; however, evidence to support this
indication is based on case reports, retrospective studies and expert opinion.
48,82,84
Figure 3
A simplified algorithm for pericardial effusion triage and management.
Unfortunately, there are no proven effective medical therapies to reduce an isolated
effusion. In the absence of inflammation, NSAIDs, colchicine and corticosteroids are
generally not effective.
82,85
Pericardiocentesis alone may be necessary for the resolution of large effusions, but
recurrences are also common, and pericardiectomy or less invasive options (i.e. pericardial
window) should be considered whenever fluid reaccumulates, becomes loculated or biopsy
material is required.
48
Recommendations for the therapy of pericardial effusion
NSAIDs = non-steroidal anti-inflammatory drugs.
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
3.5.4
Prognosis and follow-up
The prognosis of pericardial effusion is essentially related to the aetiology.
48,82,86
The size of the effusion is correlated with the prognosis, as moderate to large effusions
are more common for specific aetiologies such as bacterial and neoplastic conditions.
9,48
Idiopathic pericardial effusion and pericarditis have an overall good prognosis with
a very low risk of complications, especially if the effusion is mild to moderate.
In contrast with these observations, a recently published prospective study has shown
that even with mild pericardial effusion the overall prognosis may be worse than in
age- and sex-matched controls.
87
Large idiopathic chronic effusions (>3 months) have a 30–35% risk of progression to
cardiac tamponade.
88
Also, subacute (4–6 weeks) large effusions not responsive to conventional therapy
and with echocardiographic signs of collapse of the right chambers may have an increased
risk of progression according to some authors, who recommend preventive drainage in
such cases.
89
Documented idiopathic pericarditis has a very low risk of constrictive pericarditis
despite several recurrences: here the risk is related to the aetiology and not the
number of recurrences.
36
The follow-up of pericardial effusion is mainly based on the evaluation of symptoms
and the echocardiographic size of the effusion, as well as additional features such
as inflammatory markers (i.e. CRP).
48
A mild idiopathic effusion (<10 mm) is usually asymptomatic, generally has a good
prognosis and does not require specific monitoring.
48
Moderate to large effusions (>10 mm) may worsen, and especially severe effusions may
evolve towards cardiac tamponade in up to one-third of cases. For idiopathic moderate
effusions, an appropriate timing for echocardiographic follow-up may be an echocardiogram
every 6 months. For a severe effusion, an echocardiographic follow-up may be every
3–6 months. A tailored follow-up is also warranted considering the relative stability
or evolution of the size.
48
Specific considerations on pericardial effusion in the postoperative setting are discussed
in the section on post-cardiac injury syndromes (section 5.5).
3.6
Cardiac tamponade
Cardiac tamponade is a life-threatening, slow or rapid compression of the heart due
to the pericardial accumulation of fluid, pus, blood, clots or gas as a result of
inflammation, trauma, rupture of the heart or aortic dissection.
81,84
Clinical signs in a patient with cardiac tamponade include tachycardia, hypotension,
pulsus paradoxus, raised jugular venous pressure, muffled heart sounds, decreased
electrocardiographic voltage with electrical alternans and an enlarged cardiac silhouette
on chest X-ray with slow-accumulating effusions.
81–84
A key diagnostic finding is pulsus paradoxus (conventionally defined as an inspiratory
decrease in systolic arterial pressure of >10 mmHg during normal breathing). Pulsus
paradoxus is due to exaggerated ventricular interdependence occurring in cardiac tamponade,
when the overall volume of cardiac chambers becomes fixed and any change in the volume
of one side of the heart causes the opposite changes in the other side (i.e. inspiratory
increase of venous return and right chambers with decreased volume of left chambers
and reduced systemic blood pressure). The magnitude of clinical and haemodynamic abnormalities
depends on the rate of accumulation and amount of pericardial contents, the distensibility
of the pericardium and the filling pressures and compliance of the cardiac chambers
(
Web Figure 3
). Various causes for cardiac tamponade are listed in Table 9
.
Table 9
Causes of cardiac tamponade
The stiffness of the pericardium determines fluid increments precipitating tamponade,
as illustrated by characteristic pericardial pressure–volume (strain–stress) curves:
there is an initial slow ascent, followed by an almost vertical rise (
Web Figure 3
). This steep rise makes tamponade a ‘last-drop’ phenomenon: the final increment produces
critical cardiac compression and the first decrement during drainage produces the
largest relative decompression.
80–84
In a patient with clinical suspicion of cardiac tamponade, several diagnostic tools
are required. An ECG may show signs of pericarditis, with especially low QRS voltages
and electrical alternans. Both ECG signs are generally considered to be an expression
of the damping effect of pericardial fluid and swinging heart. Echocardiography is
the single most useful diagnostic tool to identify pericardial effusion and estimate
its size, location and degree of haemodynamic impact. Also, echocardiography is used
to guide pericardiocentesis with excellent safety and efficacy. Signs of tamponade
can be identified by echocardiography: swinging of the heart, early diastolic collapse
of the right ventricle, late diastolic collapse of the right atrium, abnormal ventricular
septal motion, exaggerated respiratory variability (>25%) in mitral inflow velocity,
inspiratory decrease and expiratory increase in pulmonary vein diastolic forward flow,
respiratory variation in ventricular chamber size, aortic outflow velocity (echocardiographic
pulsus paradoxus) and inferior vena cava plethora.
2,3,82,84
CT and CMR are often less readily available and are generally unnecessary unless Doppler
echocardiography is not feasible. Cardiac catheterization is rarely used to diagnose
cardiac tamponade. It will show equilibration of average diastolic pressure and characteristic
respiratory reciprocation of cardiac pressures, i.e. an inspiratory increase on the
right and a concomitant decrease on the left—the proximate cause of pulsus paradoxus.
Except in low-pressure tamponade, diastolic pressures throughout the heart are usually
in the range of 15–30 mmHg.
The treatment of cardiac tamponade involves drainage of the pericardial fluid, preferably
by needle pericardiocentesis, with the use of echocardiographic or fluoroscopic guidance,
and should be performed without delay in unstable patients. Alternatively, drainage
is performed by a surgical approach, especially in some situations such as purulent
pericarditis or in urgent situations with bleeding into the pericardium. A triage
system (
Web Figure 4
) has been proposed by the ESC Working Group on Myocardial and Pericardial Diseases
in order to guide the timing of the intervention and the possibility of transferring
the patient to a referral centre.
84
This triage system is essentially based on expert consensus and requires additional
validation in order to be recommended in clinical practice.
Recommendations for the diagnosis and treatment of cardiac tamponade
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
3.7
Constrictive pericarditis
Constrictive pericarditis can occur after virtually any pericardial disease process,
but only rarely follows recurrent pericarditis.
37
The risk of progression is especially related to the aetiology: low (<1%) in viral
and idiopathic pericarditis, intermediate (2–5%) in immune-mediated pericarditis and
neoplastic pericardial diseases and high (20–30%) in bacterial pericarditis, especially
purulent pericarditis.
36
A few large historical series of patients with constrictive pericarditis have been
described from tertiary referral centres (Stanford, Mayo Clinic, Cleveland Clinic
and Groote Schuur Hospital) reporting cases after pericardiectomy (
Web Table 4
).
90–93
The most common reported causes in developed countries were idiopathic or viral (42–49%),
post-cardiac surgery (11–37%), post-radiation therapy (9–31%) (mostly for Hodgkin's
disease or breast cancer), connective tissue disorder (3–7%), post-infectious causes
(TB or purulent pericarditis in 3–6%) and miscellaneous causes (malignancy, trauma,
drug-induced, asbestosis, sarcoidosis, uraemic pericarditis in <10%). TB is now only
a rare cause of constrictive pericarditis in developed countries, while it is a major
cause in developing countries.
93
However, this disorder may be increasing among immigrants from underdeveloped nations
and patients with HIV infection.
3.7.1
Clinical presentation
Constrictive pericarditis is characterized by impaired diastolic filling of the ventricles
due to pericardial disease. The classic clinical picture is characterized by signs
and symptoms of right heart failure with preserved right and left ventricular function
in the absence of previous or concomitant myocardial disease or advanced forms. Patients
complain about fatigue, peripheral oedema, breathlessness and abdominal swelling.
The delay between the initial pericardial inflammation and the onset of constriction
is variable and is possibly a direct evolution from subacute/chronic pericarditis
to constrictive pericarditis.
36
Venous congestion, hepatomegaly, pleural effusions and ascites may occur. Haemodynamic
impairment of the patient can be additionally aggravated by a systolic dysfunction
due to myocardial fibrosis or atrophy in more advanced cases.
Although classic and advanced cases show prominent pericardial thickening and calcifications
in chronic forms, constriction may also be present with normal pericardial thickness
in up to 20% of the cases.
94
Pericardiectomy is equally successful in those with and without increased pericardial
thickness.
3.7.2
Diagnosis
A diagnosis of constrictive pericarditis is based on the association of signs and
symptoms of right heart failure and impaired diastolic filling due to pericardial
constriction by one or more imaging methods, including echocardiography,
95
CT, CMR, and cardiac catheterization.
2,3,96
The main differential diagnosis is with restrictive cardiomyopathy (Table 10
).
Recommendations for the diagnosis of constrictive pericarditis
CMR = cardiac magnetic resonance; CT = computed tomography.
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
Table 10
Constrictive pericarditis vs. restrictive cardiomyopathy: a brief overview of features
for the differential diagnosis (Modified from Imazio et al.
51
)
CMR = cardiac magnetic resonance; CT = computed tomography; DT= deceleration time;
ECG = electrocardiogram; LVEDP = left ventricular end-diastolic pressure; RVEDP= right
ventricular end-diastolic pressure; RVSP = right ventricular systolic pressure; S3
= third sound. Kussmaul sign is a paradoxical rise in jugular venous pressure on inspiration.
aThe systolic area index was defined as the ratio of the RV area (mmHg x s) to the
LV area (mmHg x s) in inspiration versus expiration.
96
Specific diagnostic echocardiographic criteria for the diagnosis of constrictive pericarditis
has been recently proposed by the Mayo Clinic and include: septal bounce or ventricular
septal shift with either medial e′ >8 cm/s or hepatic vein expiratory diastolic reversal
ratio >0.78 (sensitivity 87%, specificity 91%; specificity may increase to 97% if
all criteria are present with a correspondent decrease of sensitivity to 64%.
95
3.7.3
Therapy
Although the mainstay of treatment of chronic permanent cases is surgery, medical
therapy may have a role in at least three conditions. First, medical therapy of specific
aetiologies (i.e. tuberculous pericarditis) may be useful to prevent the progression
to constriction. Antituberculosis antibiotics may significantly reduce the risk of
constriction from >80% to <10%.
79,97
Second, medical therapy (generally based on anti-inflammatory drugs) may solve the
transient constriction occurring in 10–20% of cases within a few months, generally
as a temporary phenomenon during the resolution of pericarditis.
51,98,99
The detection of elevated CRP and imaging evidence of pericardial inflammation by
contrast enhancement on CT and/or CMR may be helpful to identify patients with potentially
reversible forms of constriction where empiric anti-inflammatory therapy should be
considered and may prevent the need for pericardiectomy.
100
Third, medical therapy is supportive and aimed at controlling symptoms of congestion
in advanced cases and when surgery is contraindicated or at high risk. In these cases,
medical therapy should never delay surgery, if this option is feasible, because advanced
cases have a higher mortality and a worse prognosis if surgery is delayed.
51
3.7.4
Specific forms
The classic description of chronic permanent constrictive pericarditis has been challenged
by specific forms of constrictive syndromes (i.e. transient constriction, effusive-constrictive
forms). Definitions, main differential diagnoses and treatment of the main constrictive
pericardial syndromes are summarized in Table 11
.
51
Table 11
Definitions and therapy of main constrictive pericardial syndromes (adapted from Imazio
et al.
51
)
CMP = cardiomyopathy; d.d. = differential diagnosis.
3.7.4.1
Transient constrictive pericarditis
A temporary form of constriction usually develops with pericarditis and mild effusion
and resolves with anti-inflammatory therapy within several weeks.
98,99
The typical clinical course implies the presence of acute inflammatory pericarditis
with constriction due to inflammation, which resolves once the inflammatory process
is treated.
98,99
Thus, in the absence of evidence that the condition is chronic (e.g. cachexia, atrial
fibrillation, hepatic dysfunction or pericardial calcification), patients with newly
diagnosed constrictive pericarditis who are haemodynamically stable may be given a
trial of conservative management for 2–3 months before recommending pericardiectomy.
Since the inflamed pericardium is enhanced on CT and/or CMR, multimodality imaging
with CT and CMR may be helpful to detect pericardial inflammation.
2,3,100
3.7.4.2
Effusive-constrictive pericarditis
The pericardial cavity is typically obliterated in patients with constrictive pericarditis.
Thus even the normal amount of pericardial fluid is absent. However, pericardial effusion
may be present in some cases. In this setting, the scarred pericardium not only constricts
the cardiac volume, but can also put pericardial fluid under increased pressure, leading
to signs suggestive of cardiac tamponade. This combination is called effusive-constrictive
pericarditis.
101
Effusive-constrictive pericarditis appears to be relatively uncommon in developing
countries, with only limited published data.
101
Most cases of effusive-constrictive pericarditis in developed countries are idiopathic,
reflecting the frequency of idiopathic pericardial disease in general. However, TB
is the most common cause in developing countries.
102
Other reported causes include radiation, neoplasia, chemotherapy, infection (especially
TB and purulent forms) and post-surgical pericardial disease.
102
Patients with effusive-constrictive pericarditis usually have clinical features of
pericardial effusion or constrictive pericarditis, or both. The diagnosis of effusive-constrictive
pericarditis often becomes apparent during pericardiocentesis in patients initially
considered to have uncomplicated cardiac tamponade.
101
For these reasons, it is recommended that intrapericardial pressures, right heart
pressures and systemic arterial blood pressure are monitored during elective pericardiocentesis
whenever possible. A persistently elevated right atrial pressure after efficient pericardiocentesis
may also be due to right heart failure or tricuspid regurgitation.
However, non-invasive imaging may be equally useful for the diagnosis of effusive-constrictive
pericarditis.
102
The epicardial layer of pericardium, which is responsible for the constrictive component
of this process, is not typically thickened to a degree that is detectable on imaging
studies. Nevertheless, careful detection of Doppler findings of constriction can be
reported following pericardiocentesis for cardiac tamponade, and effusive-constrictive
pericarditis can also be suspected in these cases without haemodynamic monitoring.
Useful data may also be provided by CMR. The utility of CMR in constrictive pericardial
disease is well established, providing the opportunity not only to evaluate pericardial
thickness, cardiac morphology and function, but also for imaging intrathoracic cavity
structures, allowing the differentiation of constrictive pericarditis from restrictive
cardiomyopathy. Assessment of ventricular coupling with real-time cine magnetic resonance
during free breathing allows an accurate evaluation of ventricular interdependence
and septal bounce.
2,3
Since it is the visceral layer of pericardium and not the parietal layer that constricts
the heart, visceral pericardiectomy must be performed. However, the visceral component
of the pericardiectomy is often difficult, requiring sharp dissection of many small
fragments until an improvement in ventricular motion is observed. Thus pericardiectomy
for effusive-constrictive pericarditis should be performed only at centres with experience
in pericardiectomy for constrictive pericarditis.
101
3.7.4.3
Chronic constrictive pericarditis
Pericardiectomy is the accepted standard of treatment in patients with chronic constrictive
pericarditis who have persistent and prominent symptoms such as NYHA class III or
IV. However, surgery should be considered cautiously in patients with either mild
or very advanced disease and in those with radiation-induced constriction, myocardial
dysfunction or significant renal dysfunction. Surgical removal of the pericardium
has a significant operative mortality ranging from 6 to 12%.
103–105
Pericardiectomy must be as complete as is technically feasible and should be performed
by experienced surgeons. Referral to a centre with a special interest in pericardial
disease may be warranted in centres with limited experience in this surgery.
Patients with ‘end-stage’ constrictive pericarditis derive little or no benefit from
pericardiectomy, and the operative risk is inordinately high. Manifestations of end-stage
disease include cachexia, atrial fibrillation, a low cardiac output (cardiac index
<1.2 l/m2/min) at rest, hypoalbuminaemia due to protein-losing enteropathy and/or
impaired hepatic function due to chronic congestion or cardiogenic cirrhosis.
Prior ionizing radiation is associated with a poor long-term outcome, because it induces
cardiomyopathy as well as pericardial disease. Predictors of poor overall survival
are prior radiation, worse renal function, higher pulmonary artery systolic pressure,
abnormal left ventricular systolic function, lower serum sodium level and older age.
Pericardial calcification had no impact on survival.
103–105
Survival after radical pericardiectomy in patients with Child–Pugh (CP) B or C (CP
score ≥7) was reported to be significantly worse than in patients with CP-A. In multivariable
analysis, a CP score ≥7, mediastinal irradiation, age and end-stage renal disease
(ESRD) identified an increased risk of death after radical pericardiectomy.
106
On this basis, it seems appropriate to apply the CP scoring system for the prediction
of mortality after radical pericardiectomy in patients with constrictive pericarditis.
Recommendations for therapy of constrictive pericarditis
CMR = cardiac magnetic resonance; CRP = C-reactive protein; CT = computed tomography.
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
4.
Multimodality cardiovascular imaging and diagnostic work-up
4.1
Multimodality imaging
4.1.1
Chest X-ray
Although chest X-ray can detect pericardial calcifications, presenting as a curvilinear
density at the extreme margin of the silhouette, particularly on the lateral view,
107
other techniques (i.e. echocardiography, CT) yield much greater accuracy in assessing
the heart and lungs, providing information with regard to cardiac size and the presence
of pulmonary pathology (e.g., pulmonary congestion, pneumonia, TB, lung cancer), pleural
effusion and hilar and mediastinal enlargement.
4.1.2
Echocardiography
Transthoracic echocardiography is the first-line imaging test in patients with suspected
pericardial disease, because it accurately detects pericardial effusion and cardiac
tamponade, as well as ventricular dysfunction due to myocardial involvement.
2,3
Although patients with purely fibrinous acute pericarditis may have a normal echocardiogram,
the presence of a pericardial effusion is consistent with acute pericarditis and is
one of the criteria for its diagnosis.
2,5,6,10,11
Echocardiography may help to differentiate acute pericarditis from myocardial ischaemia
by excluding wall motion abnormalities consistent with coronary flow distribution
in the setting of patients with acute chest pain. However, ∼5% of patients with acute
pericarditis and myocardial involvement may demonstrate wall motion abnormalities.
Clinically, two-dimensional echocardiography with Doppler provides the most cost-effective
way of diagnosing pericardial effusion and assessing its haemodynamic significance.
48
The size of pericardial effusion on two-dimensional echocardiography is qualitatively
assessed by the end-diastolic distance of the echo-free space between the epicardium
and parietal pericardium: small (<10 mm), moderate (10–20 mm), large (>20 mm) (
Web Figure 2
).
48
In order to allow follow-up studies, it is recommended that the images be documented
digitally and the effusion size described in a detailed way in the echocardiographic
report, including not only the extent, but also the location of each measurement.
However, the haemodynamic tolerance is more related to the rapidity of appearance
of the effusion than to its total volume.
48,80
Loculated pericardial effusions or pericardial effusions that contain clots (e.g.
after cardiac surgery) may be difficult to diagnose using a transthoracic approach
and may require transoesophageal echocardiography.
3,4
Specific findings in pericardial syndromes are discussed in the pertinent paragraphs.
4.1.3
Computed tomography
CT should be regarded as a valuable complementary imaging modality to echocardiography.
3,4,41,108,109
CT is the most accurate technique to image calcified tissue.
2,3
Current multidetector CT scanners combine acquisition speed, high contrast and spatial
resolution with volumetric scanning to provide excellent anatomical detail of the
heart and pericardium. The anatomical region of interest covered by CT can be limited
to the heart and pericardium (‘cardiac CT’), although in patients with neoplastic,
inflammatory or aortic disease it may encompass the chest entirely and possibly also
include the abdomen and pelvis.
108,109
Low-radiation cardiac CT is feasible using prospective electrocardiographic triggering.
108,109
Although the functional consequences of pericardial disease on the heart can be evaluated
by CT—at the expense of significantly higher radiation doses—echocardiography and
CMR are more appropriate for assessing this feature. Intravenous administration of
iodinated contrast material is recommended to increase the density of blood and to
depict pericardial inflammation. The normal pericardium is visible as a thin curvilinear
structure surrounded by the hypodense mediastinal and epicardial fat, and has a thickness
ranging from 0.7 to 2.0 mm. The pericardial sinuses and their respective recesses
are visible, in particular when they contain small amounts of pericardial fluid. The
main CT findings in pericardial effusion and pericarditis are summarized in Table
12
.
41,108,109
Table 12
Diagnostic contribution of the different imaging modalities in various pericardial
diseases
CMR = cardiac magnetic resonance; CT = computed tomography; HU = Hounsfield units;
IVC = inferior vena cava; LGE= late gadolinium enhancement; LV = left ventricle; RV
= right ventricle.
In patients with neoplastic disease, pericardial involvement may occur by direct tumour
invasion or metastatic spread. CT is important in treatment planning and patient follow-up.
The diagnosis of (congenital) pericardial cysts—presenting as well-defined, fluid-dense
structures along the left or right heart border—as well as the differential diagnosis
with other cystic structures, such as bronchogenic or duplication cysts, is usually
straightforward. Finally, CT can be helpful to establish the diagnosis in congenital
absence of the pericardium by showing displacement of cardiac structures through the
pericardial defect. CT is also essential in the preoperative workup of some patients
with constrictive pericarditis, especially to depict the extension of calcifications
and for those with a history of prior cardiothoracic surgery.
109
4.1.4
Cardiac magnetic resonance
Over the years, CMR has shifted from a morphologic imaging modality towards a comprehensive
one, allowing visualization and tissue characterization of the pericardium (and heart)
in patients with pericardial disease and appraisal of the consequences of pericardial
abnormalities on cardiac function and filling patterns.
110,111
As such, it is probably the preferred imaging modality to optimally assess pericardial
disease.
112,113
Cardiac and pericardial morphology are evaluated by dark-blood T1-weighted fast spin-echo
and bright-blood cine steady-state free-precession (SSFP) imaging. Cine SSFP imaging
has become the reference sequence to assess and quantify cardiac volumes, myocardial
mass and ventricular function. When acquired in real-time, this sequence can be used
to assess ventricular coupling by assessing the changes in ventricular septal shape
and motion over the respiratory cycle.
109,110
Tissue characterization of the heart and pericardium is achieved by dark-blood T1-weighted
and dark-blood T2-weighted, short-tau inversion-recovery (STIR) spin-echo imaging,
cine SSFP imaging and T1-weighted contrast-enhanced and/or late contrast-enhanced
(LCE) imaging following intravenous administration of paramagnetic gadolinium chelates.
3,4,114
The LCE sequence uses an inversion-recovery pre-pulse to increase image contrast and
is well suited to visualize pericardial inflammation.
114,115
Ventricular inflow and venous flow patterns can be evaluated using phase contrast
imaging.
111
Similar to CT, the normal pericardium appears on T1-weighted imaging as a thin hypointense
(‘dark’) curvilinear structure surrounded by hyperintense (‘bright’) mediastinal and
epicardial fat. Normal pericardial thickness ranges from 1.2 to 1.7 mm. The imaging
characteristics of pericardial effusion and pericarditis at CMR are shown in Table
12
. It should be emphasized that CMR can accurately distinguish between mixed myopericardial
diseases such as mixed inflammatory forms (e.g. myopericarditis or perimyocarditis)
and post-myocardial infarction pericardial injury.
116,117
In patients with constrictive pericarditis, CMR is particularly important in the diagnosis
of atypical presentations, such as those with minimally thickened pericardium or effusive-constrictive
pericarditis, and those with potentially reversible or transient forms of constrictive
pericarditis, showing enhancement of the pericardial layers at LCE imaging.
115,118,119
Compared with CT, CMR has the advantage of providing information with regard to the
haemodynamic consequences of the non-compliant pericardium on cardiac filling,
109–111
and has the potential of showing fibrotic fusion of pericardial layers.
120
In patients with congenital pericardial pathology and pericardial malignancy, CMR
shares the advantages of CT, but allows better tissue characterization and the possibility
of evaluating the functional consequences.
121
Moreover, novel techniques, such as diffusion-weighted and dynamic contrast-enhanced
magnetic resonance imaging, open perspectives for improved tissue characterization
in patients with pericardial tumours.
122
4.1.5
Nuclear medicine
In selected cases, positron emission tomography (PET) alone, or preferably in combination
with CT (PET/CT), can be indicated to depict the metabolic activity of pericardial
disease. Pericardial uptake of 18F-fluorodeoxyglucose (FDG) tracer in patients with
solid cancers and lymphoma is indicative of (malignant) pericardial involvement, thus
providing essential information on the diagnosis, staging and assessment of the therapeutic
response.
123
The uptake is usually intense and often associated with a focal soft tissue mass.
124
PET/CT is also of value in identifying the nature of inflammatory pericarditis. In
particular, tuberculous pericarditis yields higher FDG uptakes than idiopathic forms.
125
However, differentiation between benign and malignant pericardial disease, as well
as differentiation between physiological and pathological cardiac FDG uptake by PET/CT,
remains challenging.
123
4.1.6
Cardiac catheterization
Cardiac catheterization is not routinely used for the diagnosis of pericardial disease,
as current non-invasive techniques are usually able to solve the differential diagnosis
of a patient with the suspicion of heart disease involving the pericardium. However,
right heart catheterization may be useful in certain circumstances. Early recognition
of abnormal haemodynamics related to cardiac tamponade during invasive procedures
(i.e. epicardial ablation, percutaneous aortic valve implantation, complex angioplasty
or complex procedures involving trans-septal punctures, among others) may help avoid
serious consequences for the patient. In addition, the differentiation between constrictive
pericarditis and restrictive cardiomyopathy is sometimes difficult and may require
an invasive test.
In cardiac tamponade, the right atrial pressure waveform has an attenuated or an absent
Y-descent. Absent Y-descent is secondary to diastolic equalization of pressures in
the right atrium and right ventricle and lack of effective flow across the tricuspid
valve in early ventricular diastole. Also, equalization of mean right atrial, right
ventricular and pulmonary artery diastolic pressures and mean pulmonary capillary
wedge pressures can be present. Other haemodynamic abnormalities include elevation
of filling pressures in all four cardiac chambers, right ventricle and left ventricle
peak systolic pressures out of phase, peak aortic pressure varying more than 10–12
mmHg and a decrease in cardiac output.
126,127
The differentiation of constrictive pericarditis from restrictive cardiomyopathy remains
difficult. Visualization of the pericardium by CT or CMR may help in detecting an
abnormal pericardium. But these tests provide anatomical information and do not necessarily
reflect the pathophysiological abnormality present. Also, patients with surgically
proven constrictive pericarditis may have a normal-appearing pericardium on imaging
studies. Alternatively patients may have abnormal pericardial thickness in the absence
of constriction, especially after radiation therapy or prior cardiac surgery. Classically,
direct measurements of pressures show M- or W-shaped atrial pressure waveforms and
‘square root’ or ‘dip-and-plateau’ right ventricular pressure waveforms, reflecting
impaired ventricular filling. End-diastolic pressure equalization (typically within
5 mmHg) occurs between these cardiac chambers in constrictive pericarditis because
of the fixed and limited space within the thickened and stiff pericardium. Pulmonary
artery systolic pressures are usually normal in pericardial constriction; higher pulmonary
pressures suggest a restrictive cardiomyopathy.
126
Recently a novel haemodynamic parameter has been tested to differentiate both entities.
96
Specifically, the ratio of the right ventricular to left ventricular systolic pressure–time
area during inspiration versus expiration (systolic area index) was used as a measurement
of enhanced ventricular interaction. In patients with surgically documented constrictive
pericarditis, during inspiration there is an increase in the area of the right ventricular
pressure curve compared with expiration. The area of the left ventricular pressure
curve decreases during inspiration as compared with expiration. In contrast, patients
with restrictive myocardial disease documented by endomyocardial biopsy usually present
a decrease in the area of the right ventricular pressure curve during inspiration
as compared with expiration. The area of the left ventricular pressure curve is unchanged
during inspiration as compared with expiration. This systolic area index presented
a 97% sensitivity and 100% predictive accuracy for identifying patients with surgically
proven constrictive pericarditis.
96
4.1.7
Multimodality imaging
Echocardiography, cardiac CT and CMR are often used as complementary imaging modalities
(Table 13
). The choice of one or multiple imaging modalities is driven by the clinical context
or condition of the patient. A modern approach for the management of pericardial diseases
should include the integration of different imaging modalities in order to improve
the diagnostic accuracy and clinical management of patients.
2,3
Table 13
Comparison of non-invasive imaging modalities to study the pericardium
CMR = cardiac magnetic resonance magnetic resonance; CT = computed tomography; ECG
= electrocardiogram; TTE = transthoracic echocardiography. (-) not possible or poor;
(+) moderate; (++) good; (+++) excellent.
aIonizing radiation, potential nephrotoxicity of contrast medium, allergic reactions
to contrast.
bPatients with metallic implants, claustrophobia, potential nephrotoxicity of contrast
medium, allergic reactions to contrast, restricted only to haemodynamically stable
patients.
cUse of ECG synchronized data acquisition.
4.2
Proposal for a general diagnostic work-up
In the management of pericardial syndromes, a major controversy is the role of an
extensive aetiological search and admission for all patients with pericarditis or
pericardial effusion.
1,4,6,51
The epidemiological background is essential to develop a rational cost-effective management
programme and the clinician should especially identify causes that require targeted
therapies.
4,5,51,128–130
The approach may be different for research, when we attempt to reduce the number of
‘idiopathic’ cases. The diagnosis of idiopathic cases is essentially an exclusion
diagnosis, supported by a typical clinical course.
On this basis, auscultation, ECG, echocardiography, chest X-ray, routine blood tests,
including markers of inflammation (i.e., CRP and/or ESR) and myocardial lesions (CK,
troponins), are recommended in all cases of suspected pericarditis. Additional testing
should be related to the suspected origin and clinical presentation.
5,6,128–130
The major specific causes to be ruled out are bacterial pericarditis (especially TB),
neoplastic pericarditis and pericarditis associated with a systemic disease (generally
an autoimmune disease) (
Web Table 5
).
9,77,129–131
Each of these specific causes has a frequency of ∼5% of all unselected cases of pericarditis
from developed countries (
Web Table 5
),
9,77,129–131
while frequencies increase in moderate to large pericardial effusions (
Web Table 3
).
8,74–78
Emerging additional causes include iatrogenic ones (percutaneous coronary interventions,
pacemaker insertion, catheter ablation).
132
The aetiological spectrum is different in developing countries with a high prevalence
of TB (e.g. 70–80% of pericarditis in sub-Saharan Africa, and often associated with
HIV infection).
52,79
Certain clinical features at presentation may be associated with an increased risk
of specific aetiologies (non-viral or non-idiopathic) and complications during follow-up
(recurrences, tamponade, constriction) and are suggested as ‘high-risk features’ useful
for the triage of pericarditis to establish the need for a full aetiological search
and admission in a single patient (Figure 1
,
Web Table 6
).
8,9
Factors indicated as ‘major’ have been validated by multivariate analysis, while factors
indicated as ‘minor’ are based on expert opinion and literature review:
9
they are essentially theoretical risk factors for complications and suggest the indication
for admission and close monitoring of the evolution. Major risk factors include fever
>38°C [hazard ratio (HR) 3.56], subacute course (symptoms developing over several
days or weeks; HR 3.97), large pericardial effusion (diastolic echo-free space >20
mm in width) or cardiac tamponade (HR 2.15) and failure of aspirin or NSAIDs (HR 2.50).
9
Large effusion and tamponade (HR 2.51) and aspirin or NSAIDs failure (HR 5.50) also
identify an increased risk of complications during follow-up (recurrences, tamponade,
constriction).
9
Minor risk factors are pericarditis associated with myocarditis, immunodepression,
trauma and oral anticoagulant therapy.
For patients with predictors of poor prognosis, major or minor (Figure 1
), hospitalization and a full aetiological search are warranted.
5,6,8,9,128
In contrast, when these negative predictors are absent, patients are at low risk of
specific causes and complications, and outpatient management may be considered.
8
This approach is safe without an excess of complications and new unexpected diagnoses
requiring a specific therapy.
8,9,128
The same approach is also useful for patients with recurrences who may generally be
treated as outpatients, unless predictors of poor prognosis are present or a specific
cause can be ruled out. With a clear diagnosis of idiopathic origin and a recurrence
course with complete symptom-free periods between the episodes, it is also unnecessary
to repeat a new aetiological search at each recurrence unless new clinical features
become evident. First- and second-line general investigations are reported in the
recommendations and Tables 14–16
.
Recommendations for the general diagnostic work-up of pericardial diseases
CK = creatine kinase; CMR = cardiac magnetic resonance; CRP = C-reactive protein;
CT = computed tomography; ECG = electrocardiogram; ESR = erythrocyte sedimentation
rate; NSAIDs = non-steroidal anti-inflammatory drugs.
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
Table 14
First and second level investigations for pericarditis
CK = creatine kinase; CMR = cardiac magnetic resonance; CRP = C-reactive protein;
CT = computed tomography; ECG = electrocardiogram; ESR = erythrocyte sedimentation
rate.
Table 15
Main analyses to be performed on pericardial fluid
LDH = lactate dehydrogenase; TB = tuberculosis.
aHigh values of protein and LDH are commonly interpreted as an exudate, as in pleural
fluid, but have not been validated for pericardial fluid.
Table 16
Suggested diagnostic flowchart in some common conditions in high risk patients
ACE = angiotensin-converting enzyme; ANA = anti-nuclear antibodies; ANCA = anti-neutrophil
cytoplasm antibodies; BNP = brain natriuretic peptide; CEA = carcinoembryonic antigen;
CMV = cytomegalovirus; CT = computed tomography; EBV = Epstein-Barr virus; ENA = anti-extractable
nuclear antigens; FMF = familial Mediterranean fever; HCV = hepatitis C virus; HHV
= human herpesvirus; HIV = human immunodeficiency virus; IGRA = interferon-gamma release
assay; MR = magnetic resonance; PCR = polymerase chain reaction; PET = positron emission
tomography; spp = species; TB = tuberculosis; TRAPS = tumour necrosis factor receptor-associated
periodic syndrome; TSH = thyroid stimulating hormone.
aConsider storage of a sterile sample for further analyses.
bSee viral pericarditis section—at present, these investigations have no therapeutic
or prognostic implications.
IGRAs are whole-blood tests that can aid in diagnosing Mycobacterium tuberculosis
infection. They do not help to differentiate latent TB infection from TB disease.
5.
Specific aetiologies of pericardial syndromes
5.1
Viral pericarditis
5.1.2
Definition and clinical spectrum
Most cases of acute pericarditis in developed countries are based on viral infections
or are autoreactive.
5,6,133–135
Acute viral pericarditis often presents as a self-limited disease, with most patients
recovering without complications.
5,6,9,36
However, as a consequence of acute viral pericarditis, cardiac tamponade, recurrent
pericarditis and, more rarely, constrictive pericarditis may also develop.
36
5.1.3
Pathogenesis
Cardiotropic viruses can cause pericardial and myocardial inflammation via direct
cytolytic or cytotoxic effects (e.g. enteroviruses) and/or via T and/or B cell–driven
immune-mediated mechanisms (e.g. herpesviruses). Persistence of viral nucleic acid
without virus replication in the peri(myo)cardium is known to sustain ongoing inflammation
and effusions via (auto)immune processes directed against specific cardiac proteins
by molecular mimicry.
133
5.1.4
Diagnosis
The definite diagnosis of viral pericarditis requires a comprehensive workup of histological,
cytological, immunohistological and molecular investigations in pericardial fluid
and peri-/epicardial biopsies obtained in conjunction with pericardioscopy, permitting
the evaluation of possible algorithms for a causative therapy.
133
In contrast, serological tests were found to be futile in the diagnosis of viral pericarditis.
Whereas no up-regulation of pro-inflammatory cytokine expression is noted in the serum,
TNF-α, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF),
IL-6, IL-8 and interferon-gamma (IFN-γ) are increased in the pericardial effusions
of patients with pericarditis, indicating the presence of local inflammatory reactions.
134,135
Accordingly, there is no correlation of antiviral antibodies in the serum or virus
isolation from throat or rectal swabs with positive molecular polymerase chain reaction
(PCR)/in situ hybridization analyses for the detection of cardiotropic viruses in
pericardial tissue and fluid.
136
5.1.5
Identification of viral nucleic acids
Mainly by quantitative PCR techniques, nucleic acids of different cardiotropic RNA
and DNA viruses have been detected in epicardial and pericardial biopsies and the
pericardial fluid of children and adults with acute pericarditis, but also in patients
with recurring and constrictive pericarditis.
133,137
Regarding RNA viruses, various subtypes of enteroviruses including echoviruses and
coxsackieviruses of groups A (A4, A16) and B (CVB2, CVB3, CVB4) were identified in
patients with acute and constrictive pericarditis.
137,138
Among the RNA viruses, influenza A viruses (e.g. H1N1, H5N1, H3N2) and occasionally
chikungunya virus, human coronavirus NL-63, respiratory syncytial virus and dengue
virus infections were suspected as aetiopathogenic agents in pericarditis.
Compared with RNA viruses, nucleic acids of DNA viruses, including parvovirus B19
and herpesviruses [Epstein–Barr virus (EBV) and human herpesvirus 6 (HHV-6)], are
present in pericardial biopsies and pericardial fluid at greater frequencies and higher
viral DNA copy numbers.
133
Whereas parvovirus B19, with up to 7 × 10
6
GE/lg DNA was predominantly detected in epicardial tissue, EBV was most frequently
found in pericardial fluid.
133
DNA of varicella zoster virus, herpes simplex virus and adenoviruses is only rarely
detected in pericarditis patients. Cytomegalovirus (CMV)-associated pericarditis is
mainly found in immunocompromised and HIV patients.
1
In developing countries with a delayed roll-out of antiretroviral therapy, HIV-associated
inflammatory reactions (often related to TB) of the pericardium and myocardium are
common complications.
139
However, at present these investigations are usually not performed because of their
complexity, cost, invasive nature and low availability.
5.1.6
Therapy
Acute viral pericarditis often presents as a self-limiting disease that responds well
to a short course of treatment with NSAIDs, with the adjunct of colchicine, especially
for prevention of recurrences.
4–6,50,58,59
The identification of specific viral signatures aids in understanding the pathogenetic
mechanisms in pericarditis, and might enable an individualized aetiologically driven
specific treatment approach to be established by distinguishing a viral aetiology
from autoreactive inflammation.
133
Some experts suggest antiviral treatment similar to that for myocarditis (IVIG therapy
in acute systemic enteroviral, CMV, EBV and parvovirus B19 infection, oral valganciclovir
in HHV-6 perimyocarditis, IFN-α for enteroviral pericarditis).
133
However, these treatments are still under evaluation and rarely used. Involvement
of infectious disease specialists is recommended. So far, no therapy is available
to solve the problem of virus persistence and consecutive inflammation, particularly
when induced by herpesviruses and parvovirus B19 infections.
133
Importantly, corticosteroids are generally not indicated in viral pericarditis, as
they are known to reactivate many virus infections and thus lead to ongoing inflammation.
133
Recommendations for the diagnosis and therapy of viral pericarditis
HCV = hepatitis C virus; HIV = human immunodeficiency virus.
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
dIn the absence of such an argument, the term ‘presumed viral pericarditis’ should
be used.
5.2
Bacterial pericarditis
Bacterial pericarditis is relatively uncommon in clinical practice in developed countries
with a low prevalence of TB. Tuberculous pericarditis is the most common form all
over the world and the most common cause of pericardial diseases in developing countries.
We will discuss this form and also purulent pericarditis, which is less common.
5.2.1
Tuberculous pericarditis
Tuberculous pericarditis accounts for ≤4% of pericardial disease in the developed
world.
5,6,52
. In contrast, TB is the cause of clinically significant pericardial effusion in >90%
of HIV-infected and 50–70% of non-HIV-infected individuals who live in developing
countries where TB is endemic.
77
The disease can occur at any age, and men are affected more frequently than women.
140
Clinical evidence of chronic cardiac compression mimicking congestive heart failure
is the most common presentation.
79,93
Clinical presentations are pericardial effusion, effusive-constrictive pericarditis
and constrictive pericarditis.
79
Tuberculous pericarditis has a mortality rate of 17–40% at 6 months after diagnosis.
141
It should be emphasized that the majority of the information on tuberculous pericarditis
comes from endemic areas in underdeveloped countries and immunodepressed patients.
The applicability of this information to the Western world is questionable.
5.2.1.1
Diagnosis
A ‘definite’ diagnosis of tuberculous pericarditis is based on the presence of tubercle
bacilli in the pericardial fluid or on histological section of the pericardium, by
culture or by PCR (Xpert MTB/RIF) testing; a ‘probable’ diagnosis is made when there
is proof of TB elsewhere in a patient with unexplained pericarditis, a lymphocytic
pericardial exudate with elevated unstimulated interferon-gamma (uIFN-γ), adenosine
deaminase (ADA) or lysozyme levels and/or an appropriate response to antituberculosis
chemotherapy in endemic areas.
79
uIFN-γ offers superior accuracy for the diagnosis of microbiologically confirmed tuberculous
pericarditis compared with the ADA assay and the Xpert MTB/RIF test.
142
A protocol for the evaluation of suspected tuberculous pericardial effusion is proposed
in Table 17
.
Table 17
A step-wise protocol for the evaluation of suspected tuberculous pericarditis and
pericardial effusion
ADA = adenosine deaminase; CT = computed tomography; LDH = lactate dehydrogenase;
MRI = magnetic resonance imaging; TB = tuberculosis.
5.2.1.2
Management
A regimen consisting of rifampicin, isoniazid, pyrazinamide and ethambutol for at
least 2 months followed by isoniazid and rifampicin (total of 6 months of therapy)
is effective in treating extrapulmonary TB. Treatment for ≥9 months gives no better
results and has the disadvantages of increased cost and increased risk of poor compliance.
143
The evolution towards constrictive pericarditis is a serious potential complication.
Constriction generally develops within 6 months of presentation with effusive pericarditis
(effusive-constrictive pericarditis).
79
Tuberculous pericardial constriction is almost always associated with pericardial
thickening. Prior to the introduction of effective TB chemotherapy, up to 50% of patients
with effusive tuberculous pericarditis progressed to constriction. Rifampicin-based
antituberculosis treatment reduced the incidence of constriction to 17–40%. Appropriate
antibiotic therapy is essential to prevent this progression.
79,144
In addition, two interventions may reduce the incidence of constriction: the first
is intrapericardial urokinase
145
and second, the Investigation of the Management of Pericarditis (IMPI) trial has shown
that high-dose adjunctive prednisolone reduces the incidence of constrictive pericarditis
by 46% regardless of HIV status.
97
Adjunctive corticosteroid therapy with prednisolone for 6 weeks had a neutral effect
on the combined outcome of death from all causes, cardiac tamponade requiring pericardiocentesis
or pericardial constriction; however, this therapy was associated with an increased
risk of HIV-associated malignancies in the prednisolone-treated group.
97
Adjunctive steroid therapy was associated with a reduced incidence of pericardial
constriction and hospitalization. The beneficial effects of prednisolone on constriction
and hospitalization were similar in HIV-positive and HIV-negative patients. On this
basis, it may be reasonable to use adjunctive corticosteroids in patients with tuberculous
pericarditis without HIV infection and to avoid them in HIV-infected individuals because
of the increased risk of malignancy.
97
Recommendations for the diagnosis and treatment of tuberculous pericarditis and effusion
HIV = human immunodeficiency virus; TB = tuberculosis.
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
Recommendations for the general management of constrictive tuberculous pericarditis
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
5.2.2
Purulent pericarditis
5.2.2.1
Epidemiology
Purulent pericarditis is rare, accounting for <1% of cases.
5,6
In Western series, the most common organisms have been staphylococci, streptococci
and pneumococci, while the predominant associated lesions were empyema (50%) or pneumonia
(33%).
146
In immunosuppressed patients or following thoracic surgery, Staphylococcus aureus
(30%) and fungi (20%) are more common.
147
Also, anaerobes originating from the oropharynx have been reported.
148
Seeding may be haematogenous or by contiguous spread from the retropharyngeal space,
cardiac valves and below the diaphragm.
149
Neisseria meningitidis may involve the pericardium either through initiating an immune-mediated
sterile effusion or by direct infection and purulent reaction. The modern era of iatrogenic
and HIV-associated immunosuppression has witnessed more unusual organisms.
5.2.2.2
Diagnosis
Purulent pericarditis is rare and generally manifested as a serious febrile disease.
The underlying sepsis may predominate the illness.
146–149
Suspicion of purulent pericarditis is an indication for urgent pericardiocentesis,
1,5,12
which is diagnostic. The fluid may be frankly purulent. A low pericardial:serum glucose
ratio (mean 0.3) and elevated pericardial fluid white cell count with a high proportion
of neutrophils (mean cell count 2.8/μl, 92% neutrophils) differentiate purulent from
tuberculous (glucose ratio 0.7, count 1.7/μl, 50% neutrophils) and neoplastic (glucose
ratio 0.8, count 3.3/μl, 55% neutrophils) pericarditis.
150
Fluid should be sent for bacterial, fungal and tuberculous studies, with blood for
cultures and other samples being taken as guided by the clinical presentation.
12
5.2.2.3
Management
Purulent pericarditis should be managed aggressively, as death is inevitable if untreated,
whereas with comprehensive therapy 85% of cases have been reported to survive the
episode and have a good long-term outcome.
50,146
Intravenous antimicrobial therapy should be started empirically until microbiological
results are available. Drainage is crucial. Purulent effusions are often heavily loculated
and likely to rapidly re-accumulate. Intrapericardial thrombolysis is a possible treatment
for cases with loculated effusions in order to achieve adequate drainage before resorting
to surgery.
151
Subxiphoid pericardiostomy and rinsing of the pericardial cavity should be considered.
1
This allows more complete drainage of the effusion, as loculations can be manually
lysed.
Recommendations for the diagnosis of purulent pericarditis
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
Recommendations for the therapy of purulent pericarditis
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
5.3
Pericarditis in renal failure
Renal disease and overall ESRD are associated with possible pericardial involvement.
152
Three different pathologies are found in uraemic patients: uraemic pericarditis—before
renal replacement therapy or within 8 weeks of its initiation; dialysis pericarditis—after
being stabilized on dialysis (usually ≥8 weeks after its initiation)
153
and, very rarely, constrictive pericarditis. The global incidence of pericarditis
in ESDR patients has declined to ∼5% in those patients starting dialysis.
152
The reported frequency of dialysis pericarditis ranges from 2 to 21%, but recent data
are lacking.
Pericardial involvement in ESRD is manifested most commonly as acute pericarditis
and chronic pericardial effusion and infrequently as chronic constrictive pericarditis.
Typical features of this form of pericarditis include a lower rate of pleuritic chest
pain (up to 30% of patients are asymptomatic) and the absence of ECG abnormalities
in most cases, probably due to the lack of myocardial inflammation.
152–154
Patients with ESRD are more likely to develop chronic pericardial effusion due to
continuous volume overload.
152
Not all pericardial effusions result from inflammation, and the normal volume of pericardial
fluid is larger in stable haemodialysis patients than in normal controls.
155
With the advent of advanced renal replacement therapy, the incidence of haemodynamically
significant effusions has decreased.
152,156,157
The most probable cause of uraemic pericarditis is the retention of toxic metabolites.
152,157
Since pericardial effusion is often bloody in uraemic patients, anticoagulation should
be carefully considered or avoided in patients starting dialysis.
152,157
Recommendations for the management of pericarditis in renal failure
NSAIDs = non-steroidal anti-inflammatory drugs.
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
5.4
Pericardial involvement in systemic autoimmune and autoinflammatory diseases
Pericardial involvement in systemic autoimmune diseases may be symptomatic (pericarditis
and symptomatic pericardial effusion) or asymptomatic (usually pericardial effusion)
and generally reflects the degree of activity of the underlying disease.
45
Approximately 5–15% of patients with acute or recurrent pericarditis may have a systemic
autoimmune disease, either overt or underlying (Table 1
,
Web Table 5
).
9,77,129–131
Pericardial involvement is common in systemic lupus erythematosus, Sjögren's syndrome,
rheumatoid arthritis and scleroderma, but may also be present in systemic vasculitides,
Behçet's syndrome, sarcoidosis and inflammatory bowel diseases. Pericardial involvement
rarely occurs as the first manifestation of these diseases. In most patients the underlying
disease has already been diagnosed by classical symptoms and signs. Concomitant myocardial
inflammatory involvement may complicate the presentation and should be ruled out.
If clinical features suggest a possible systemic autoimmune disease, a targeted aetiological
search is warranted in cooperation with specialist consultation. The treatment is
especially targeted at control of the systemic underlying disease.
45
A specific subset of patients includes those with periodic fevers. These are genetic
disorders characterized by mutations of genes involved in the regulation of the inflammatory
response, without involvement of specific T cells or autoantibodies.
158–161
These disorders are usually detected in the paediatric population, although some patients
experience disease onset during adulthood. The most common autoinflammatory syndromes
include familial Mediterranean fever (FMF), in which serositis episodes last only
1–3 days, and tumour necrosis factor receptor-associated periodic syndrome (TRAPS),
in which the episodes last for weeks. Mutations associated with these disorders are
rare in recurrent pericarditis.
158–161
These conditions may be characterized by an exaggerated expression of IL-1.
161
A 10% rate of familial occurrence of pericarditis has been reported among the relatives
of these patients.
162–164
These data suggest a genetic predisposition in at least a subset of patients; counselling
may be warranted in these cases. A positive family history for pericarditis or periodic
fevers, a poor response to colchicine, as well as the need for immunosuppressive agents
are clues to the possible presence of an auto-inflammatory disease;
160
particularly in these conditions, anti-IL-1 or anti-TNF agents may be considered.
31,32,160
5.5
Post-cardiac injury syndromes
The term post-cardiac injury syndromes (PCIS) is an umbrella term indicating a group
of inflammatory pericardial syndromes including post-myocardial infarction pericarditis,
post-pericardiotomy syndrome (PPS) and post-traumatic pericarditis (either iatrogenic
or not).
132
Such syndromes are presumed to have an autoimmune pathogenesis triggered by initial
damage to pericardial and/or pleural tissues caused by either myocardial necrosis
(late post-myocardial infarction pericarditis or Dressler syndrome), surgical trauma
(PPS), accidental thoracic trauma (traumatic pericarditis) or iatrogenic trauma with
or without bleeding (pericarditis after invasive cardiac interventions).
131
The immune-mediated pathogenesis is supported by a latent period generally of a few
weeks until the appearance of the first manifestations and the response to anti-inflammatory
drugs (NSAIDs, corticosteroids, colchicine) with the possibility of recurrences. Pericardial
bleeding and pleura incision are triggers for the syndrome.
165,166
Some forms, such as Dressler syndrome, have become rare with early reperfusion therapy
of myocardial infarction; however, it may occur especially in cases of even minor
bleeding into the pericardium.
167
5.5.1
Definition and diagnosis
According to proposed diagnostic criteria for PPS,
168–170
the diagnosis of PCIS may be reached after a cardiac injury following clinical criteria:
(i) fever without alternative causes, (ii) pericarditic or pleuritic chest pain, (iii)
pericardial or pleural rubs, (iv) evidence of pericardial effusion and/or (v) pleural
effusion with elevated CRP. At least two of five criteria should be fulfilled. The
rationale for proposing specific criteria instead of adopting the same for pericarditis
is that these syndromes may have concomitant pleuropericardial involvement and possible
pulmonary infiltrates, and are not simply pericarditis.
170
Moreover, it is sometimes difficult to differentiate PCIS from the simple mechanical
consequences of surgery (such as pericardial or pleural effusion). The demonstration
of inflammatory activity should be essential to establish the diagnosis. Basic diagnostic
evaluation of a patient with a suspected PCIS includes physical examination, ECG,
echocardiogram, thoracic echography and/or chest X-ray.
132,165
On this basis, echocardiography is recommended when an iatrogenic complication is
suspected after a cardiovascular intervention.
2,3,132
5.5.2
Management
Treatment of PCIS is essentially based on empiric anti-inflammatory therapy, and may
improve remission rates and reduce the risk of recurrences.
171
The same therapeutic scheme adopted for pericarditis is efficacious for all these
forms, including post-myocardial infarction pericarditis (Table 3
). Colchicine is not recommended for postoperative effusions in the absence of systemic
inflammation.
172–174
Similarly NSAIDs are generally not indicated in asymptomatic post-surgical effusions,
and this therapy may be associated with an increased risk of side effects related
to NSAIDs.
173,174
5.5.3
Prevention
Different preventive strategies have been examined in a few studies regarding aspirin,
175
methylprednisone,
176
dexamethasone
177
and colchicine.
168,169,172
Four controlled clinical trials for primary prevention of PPS were included in a systematic
review on 894 patients; three studies were double-blind RCTs. Treatment comparisons
were colchicine vs. placebo (two RCTs enrolling 471 patients), methylprednisolone
vs. placebo (one RCT involving 246 paediatric patients) and aspirin vs. historical
controls (one non-randomized study involving 177 paediatric patients). Meta-analytic
pooling showed that only colchicine was associated with decreased risk of PPS [odds
ratio (OR) 0.38]. Data on methylprednisolone (OR 1.13) and aspirin (OR 1.00) were
negative.
178
The Colchicine for Prevention of the Post-pericardiotomy Syndrome and Post-operative
Atrial Fibrillation (COPPS-2) trial confirmed the overall efficacy of perioperative
use of colchicine, but it was also found to be associated with an increased risk of
gastrointestinal side effects
172
compared with postoperative use of colchicine.
169
Colchicine is not recommended for the perioperative treatment and prevention of postoperative
effusions in the absence of systemic inflammation.
172
In another trial,
177
high-dose dexamethasone (1 mg/kg as a single intraoperative dose) was not efficacious
in preventing PPS or complicated PPS.
5.5.4
Prognosis
Despite limited published data, the prognosis of PPS is generally good.
178
There are very few available data on other forms of post-pericardial injury syndromes.
In the largest published series on PPS patients after cardiac surgery,
166
complication rates were low: <4% for recurrences, <2% for cardiac tamponade and no
cases of constriction, although hospital stay may be prolonged in these patients.
However, the development of constrictive pericarditis has been reported in ∼3% of
cases.
36
5.5.4.1
Post-myocardial infarction pericarditis
Following an acute myocardial infarction (AMI), three major pericardial complications
may occur: (i) pericardial effusion, (ii) early infarct-associated pericarditis (often
called early post-infarction pericarditis, typically a few days after AMI) and (iii)
late pericarditis or post-cardiac injury (Dressler) syndrome (typically 1–2 weeks
after AMI).
Early post-infarction pericarditis usually occurs soon after the AMI and is transient.
This complication is rare in the primary percutaneous coronary intervention era and
is especially related to late reperfusion or failed coronary reperfusion.
167
Diagnostic criteria do not differ from those for acute pericarditis. ECG changes are
usually overshadowed by changes due to the myocardial infarction. However, ST segments
may remain elevated, with persistence of upright T waves, as T waves may become upright
again after having been inverted. Echocardiography should be performed in patients
suspected of having post-AMI to evaluate for the presence of a pericardial effusion.
CMR can be used to show the presence of concomitant pericardial inflammation.
179
Patients with a post-AMI pericardial effusion >10 mm in thickness should be investigated
for a possible subacute rupture.
180,181
The treatment is generally supportive, as most cases are self-limited. However, a
minority of patients may have persistent symptoms that require more than supportive
care. For these patients, aspirin plus colchicine may be considered.
Late post-AMI pericarditis (Dressler syndrome) is rare (<1%) in the era of primary
percutaneous coronary intervention and may reflect a larger size of AMI and/or late
reperfusion.
167
Diagnosis and treatment are similar to that generally recommended for PCIS.
Although pericarditis is associated with a larger infarct size, in-hospital and 1-year
mortality and major adverse cardiac events were similar in patients with and without
pericarditis. Timely primary percutaneous coronary intervention may reduce the occurrence
of post-AMI pericarditis. Early post-AMI pericarditis remains a marker of larger infarct
size, but without independent prognostic significance.
167
5.5.4.2
Postoperative effusions
Postoperative pericardial effusions are relatively common after cardiac surgery. They
usually disappear in 7–10 days, but sometimes they persist for longer and can be dangerous.
Early post-cardiac surgery pericardial collections must be interpreted in the clinical
context of the patient. They have been reported as asymptomatic in 22% of patients
2 weeks after cardiac surgery.
182
The prognosis is good for mild effusions occurring in two of three cases, but moderate
to large effusions (one of three) may progress to cardiac tamponade in ∼10% of cases
1 month after cardiac surgery.
182,183
Treatment of these asymptomatic effusions by diclofenac was shown to be useless in
the Post-Operative Pericardial Effusion (POPE) trial and may be associated with an
increased risk of side effects related to NSAID use.
173
In contrast, cardiac tamponade occurring in the first hours after cardiac surgery
is usually due to haemorrhage in the pericardial space, and surgical reintervention
is mandatory in this situation.
Recommendations for the management and prevention of post-cardiac injury syndromes
NSAIDs = non-steroidal anti-inflammatory drugs; PCIS = post-cardiac injury syndromes;
PPS = post-pericardiotomy syndrome.
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
dAntiplatelet effects of aspirin have been demonstrated for doses up to 1.5 g/day.
There are no data for or against the use of higher doses in this setting.
5.6
Traumatic pericardial effusion and haemopericardium
Any cardiac intervention (e.g. percutaneous coronary intervention, pacemaker lead
insertion, radiofrequency ablation) may be responsible for haemopericardium and cardiac
tamponade due to coronary or cardiac chamber perforation. Pericardial effusion induced
by trauma is included in the more expanded concept of PCIS.
132
However, in the event of overt chest trauma complicated by cardiac tamponade, the
magnitude of the trauma is the main cause of the syndrome. Diagnosis includes the
presence of a prior history of chest trauma as a trigger for the syndrome plus the
signs and symptoms of pericarditis (i.e. chest pain, pericardial rub, dyspnoea, low-grade
fever) and markers of inflammatory reaction (i.e. elevated CRP, leucocytosis, ESR).
ECG is normally used to rule out AMI as a possible cause of pericarditis. Chest X-ray
may help to detect cardiomegaly and pleural effusions. Transthoracic echocardiography
is used to detect the presence, size and haemodynamic importance of the pericardial
effusion. A recent randomized trial demonstrated that the use of limited transthoracic
echocardiography improved the time from the trauma bay to the operating room and reduced
the mortality rate.
184
Therefore treatment differs according to the severity of the syndrome. For those with
post-traumatic pericarditis with no haemodynamic compromise, treatment is essentially
based on empirical anti-inflammatory therapy and adjunctive colchicine, which has
been shown to be safe and efficacious for the prevention of pericarditis.
57
For those life-threatening cases of penetrating trauma to the heart and chest, emergency
thoracotomy is recommended to improve survival as opposed to the classic strategy
of initial pericardiocentesis as a bridge to surgery.
185,186
This is usually done through left anterolateral thoracotomy that makes pericardiotomy
possible with effective relief of cardiac tamponade and direct cardiac massage if
needed.
In the setting of aortic dissection with haemopericardium and suspicion of cardiac
tamponade, emergency transthoracic echocardiography or a CT scan should be performed
to confirm the diagnosis. In such a scenario, controlled pericardial drainage of very
small amounts of the haemopericardium can be attempted to temporarily stabilize the
patient in order to maintain blood pressure at ∼90 mmHg.
187
Recommendations for the management of traumatic pericardial effusion and haemopericardium
in aortic dissection
CT = computed tomography.
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
5.7
Pericardial involvement in neoplastic disease
The differential diagnosis between malignant processes and other causes of pericarditis
is particularly relevant and generally is accomplished by imaging, e.g. CT scan, cytology
of pericardial fluid and eventually biopsies. Primary tumours of the pericardium,
either benign (lipomas and fibromas) or malignant (mesotheliomas, angiosarcomas, fibrosarcomas),
are very rare.
188,189
Mesothelioma, the most common malignant tumour, is almost always incurable. The most
common secondary malignant tumours are lung cancer, breast cancer, malignant melanoma,
lymphomas and leukaemias. Malignant pericardial effusions may be small, medium or
large, with an imminent tamponade (frequent recurrences) or constriction; they may
even be the initial sign of malignant disease.
190
The diagnosis is based on confirmation of the malignant infiltration within the pericardium.
188,189
Of note, in almost two-thirds of patients with documented malignancy, pericardial
effusion is caused by non-malignant diseases, e.g. radiation pericarditis, other therapies
or opportunistic infections.
189
Chest X-ray, CT, PET and CMR may reveal mediastinal widening, hilar masses and pleural
effusion. Analyses of pericardial fluid and pericardial or epicardial biopsies are
essential for the confirmation of malignant pericardial disease.
188–191
The diagnostic yield of the concentrations of tumour markers in pericardial fluid
remains controversial: carcinoembryonic antigen (CEA), CYFRA 21–1, neuron-specific
enolase (NSE), CA-19–9, CA- 72–4, SCC, GATA3 and VEGF may be useful, but none of these
tumour markers has been proven to be accurate enough for distinguishing malignant
from benign effusions.
192,193
Epidermal growth factor receptor (EGFR) mutation should be evaluated and has prognostic
indications in patients with malignant pericardial effusion in the course of lung
adenocarcinoma
194
in order to tailor the treatment.
Treatment of cardiac tamponade is a class I indication for pericardiocentesis. The
following steps are recommended in large suspected neoplastic pericardial effusion
without tamponade: (i) systemic antineoplastic treatment as baseline therapy,
189
(ii) pericardiocentesis to relieve symptoms and establish a diagnosis and (iii) intrapericardial
instillation of cytostatic/sclerosing agents to prevent recurrences. Pericardial drainage
is recommended in all patients with large effusions because of the high recurrence
rate (40–70%).
193–196
Prevention of recurrences may be achieved by intrapericardial instillation of sclerosing
and cytotoxic agents.
197–204
Intrapericardial treatment should be tailored to the type of tumour: cisplatin was
most effective in pericardial involvement in the course of lung cancer
200,204
and thiotepa was more effective in breast cancer pericardial metastases.
197,198
Tetracyclines as sclerosing agents also control malignant pericardial effusion in
∼85% of cases, but side effects and complications are quite frequent: fever (19%),
chest pain (20%) and atrial arrhythmias (10%).
189,199
Radiation therapy is very effective (93%) in controlling malignant pericardial effusion
in patients with radiosensitive tumours such as lymphomas and leukaemias. However,
radiotherapy of the heart can cause myocarditis and pericarditis.
189
Pericardiotomy is indicated when pericardiocentesis cannot be performed.
205
The procedure can be carried out under local anaesthesia, but complications include
myocardial laceration, pneumothorax and mortality.
189,205
Surgical pericardiotomy does not improve clinical outcomes over pericardiocentesis
and is associated with a higher rate of complications.
202
Pleuropericardiotomy allows drainage of malignant pericardial fluid into the pleural
space. It is associated with a higher complication rate and offers no advantage over
pericardiocentesis or pericardiotomy. Pericardiectomy is rarely indicated, mainly
for pericardial constriction or complications of previous procedures.
189
Percutaneous balloon pericardiotomy creates a pleuropericardial direct communication,
which allows fluid drainage into the pleural space: in large malignant pericardial
effusions and recurrent tamponade it seems to be effective (90–97%) and safe.
204
Pericardial window creation via left minithoracotomy is a safe and effective approach
in the surgical treatment of malignant cardiac tamponade.
205
In clinical practice, management is often palliative at late stages with advanced
disease; it is aimed only at the relief of symptoms rather than treatment of the underlying
disease, taking into account prognosis and the overall quality of life of the patients.
206
Recommendations for the diagnosis and management of neoplastic involvement of the
pericardium
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
5.8
Other forms of pericardial disease
5.8.1
Radiation pericarditis
Prior chest radiation is an important cause of pericardial disease. Most cases are
secondary to radiation therapy for Hodgkin's lymphoma or breast or lung cancer. Serious
radiation-induced pericardial disease was most often due to radiation therapy of Hodgkin's
lymphoma, although the incidence of the condition has decreased with lower doses and
modern radiation therapy techniques (shielding and dose calculation). As an example,
the incidence of pericarditis decreased from 20 to 2.5%.
208
Less commonly, radiation exposure can cause other conditions (e.g. oesophageal cancer)
or can occur in association with nuclear accidents. Soon after radiation the patient
may develop acute pericarditis with or without effusion.
208
Late onset of pericardial disease is common; it has been observed in up to 20% of
patients within 2 years following irradiation,
209
with a latency of up to 15–20 years, and is not necessarily preceded by acute pericarditis.
210
Late pericardial disease may consist of effusive-constrictive pericarditis or classical
constrictive pericarditis (4–20% of patients) and appears to be dose dependent and
related to the presence of pericardial effusion in the delayed acute phase.
209
Alternatively, radiation damage may result in a large pericardial effusion, with or
without tamponade. The effusion may be serous or haemorrhagic and has a high probability
of developing fibrous adhesions. Therapies are similar to those employed in pericarditis
and pericardial effusion. Therapeutic radiation may cause other types of cardiac injury
as well. The most serious is radiation-induced cardiomyopathy, but the coronary arteries
and the cardiac valves may also be affected; this probably explains why pericardiectomy
for radiation-induced disease is associated with a worse outcome than when performed
for constrictive pericarditis resulting from most other causes.
Recommendations for the prevention and management of radiation pericarditis
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
5.8.2
Chylopericardium
Chylopericardium is a pericardial effusion composed of chyle, the normal content of
the lymphatic vessels. It is a rare disorder that may be primary or, more often, secondary
to injury to the thoracic duct, which carries chyle from the intestinal tract to the
blood at the junction of the left internal jugular and left subclavian veins.
211
It is often associated with chylothorax. Cardiac complications are cardiac tamponade,
acute pericarditis and chronic constriction. Causes are trauma, surgery (especially
for congenital heart disease), congenital lymphangiomatosis, radiotherapy, subclavian
vein thrombosis, infection (e.g. TB), mediastinal neoplasms and acute pancreatitis.
212–214
Primary chylopericardium is less common and is a diagnosis by exclusion. CT with and
without contrast enhancement or combined with lymphangiography/lymphangioscintigraphy
(rarely performed) can be used to identify injury or blockage of the thoracic duct.
Chylopericardium should not be confused with cholesterol pericarditis, in which the
fluid is clear and occurs in tuberculous pericarditis, rheumatoid pericarditis and
trauma. The concentration of cholesterol equals or exceeds that of the blood. Pericardiocentesis
is seldom effective and optimal therapy is radical pericardiectomy plus treatment
of the underlying cause.
215,216
Recommendations for the diagnosis and management of chylopericardium
s.c. = subcutaneous.
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
5.8.3
Drug-related pericarditis and pericardial effusion
Pericardial reactions to drugs are rare (Table 1
). Pericardial damage has also been associated with polymer fume inhalation, ‘serum
sickness’ by blood products or foreign antisera, venoms (scorpion fish sting), foreign
substance reactions by direct pericardial application (e.g. talc, magnesium silicate),
silicones, tetracyclines, sclerosants, asbestos and iron in β-thalassaemia.
1
Management is based on discontinuation of the causative agent and symptomatic treatment.
The use of heparin and anticoagulant therapies is often perceived as a possible risk
factor for the development of a worsening or haemorrhagic pericardial effusion that
may result in cardiac tamponade, but a multivariable analysis of nearly 500 consecutive
cases of acute pericarditis did not show this to be the case.
9
Similarly in another study of 274 patients with acute pericarditis or myopericarditis,
the use of heparin or other anticoagulants was not associated with an increased risk
of cardiac tamponade.
7
On the other hand, in the setting of iatrogenic pericardial effusion, full anticoagulation
may be a risk factor for tamponade and complications.
217
5.8.4
Pericardial effusion in metabolic and endocrine disorders
The main cause of pericardial diseases in this setting is represented by hypothyroidism.
Pericardial effusion may occur in ∼5–30% of patients with hypothyroidism, but recent
data are lacking;
218,219
it may be quite large, but tamponade occurs rarely. It is diagnosed by a high thyroid
stimulating hormone (TSH) level, and clinically is characterized by relative bradycardia
and low QRS voltage in the ECG.
5.8.5
Pericardial involvement in pulmonary arterial hypertension
Pericardial effusion in the setting of pulmonary artery hypertension (PAH) is common
(25–30%) and typically small in size, but rarely causes haemodynamic compromise. Pericardial
effusion development in PAH appears to relate to right ventricular failure and a subsequent
increase in right-sided filling pressures along with right atrial hypertension and
increased pressure in the thebesian veins and coronary sinus. These processes result
in increased filtration and lymphatic obstruction, resulting in pericardial effusion.
220
Diagnosis of cardiac tamponade in a patient with severe PAH is challenging. Determining
the haemodynamic significance of pericardial effusions in PAH requires increased attention
since high right-sided pressures can mask many of the typical right-sided clinical
and echocardiographic findings of tamponade. Because there is elevation in right-sided
intracardiac chamber pressures, right-sided chamber collapse is uncommon. In contrast,
left atrial pressure is typically lower in PAH and therefore left atrial early diastolic
collapse is more commonly seen. Exaggerated ventricular interdependence, such as a
decrease in left ventricular filling with early inspiration, may also be present.
The presence of pericardial effusion has been associated with connective tissue disease,
shorter 6-minute walk distance and an elevated B-type natriuretic peptide level. Even
a small quantity of excess pericardial fluid in a patient with PAH portends a poor
prognosis. Pericardial effusions in PAH appear to be a marker of co-morbidity with
either concomitant connective tissue disease or high venous pressure; these two factors
are recognized to confer an adverse risk.
220
5.8.6
Pericardial cysts
Pericardial cysts are rare mediastinal masses with an incidence of 1 in 100,000 patients
131,221
that have been described as diverticulae or cystic formations when an abnormal chest
X-ray was obtained. They represent 6% of mediastinal masses and 33% of mediastinal
cysts. Other cysts in the mediastinum are bronchogenic (34%), enteric (12%), thymic
and others (21%).
131,221
They are often found in either one of the cardiophrenic angles.
131,206,221
Cysts do not communicate with the pericardial space, whereas diverticulae do. They
may be uni- or multiloculated. Inflammatory cysts comprise pseudocyst as well as encapsulated
or loculated pericardial effusions caused by rheumatic disorders, bacterial infection,
trauma or cardiac surgery. Echinococcal cysts usually originate from ruptured hydatid
cysts in the liver and the lungs. The differential diagnosis comprises loculated pericardial
effusions of unknown origin and malignant pericardial masses. The diagnostic workup
includes echocardiography, CT and eventually CMR to define the size, density and neighbouring
structures.
131,221
They are mostly asymptomatic and detected incidentally, but can also present with
chest discomfort, dyspnoea or palpitations due to cardiac compression. The first treatment
for symptomatic congenital and inflammatory cysts is percutaneous aspiration,
206,222
possibly associated with ethanol sclerosis.
222
If the diagnosis is not completely established by imaging or the cyst recurs after
drainage, surgical resection may be necessary. For echinococcal cysts, percutaneous
aspiration and instillation of ethanol or silver nitrate after pre-treatment with
albendazole (800 mg/day for 4 weeks) has been proposed.
1
6.
Age and gender issues in pericardial diseases
6.1
Paediatric setting
Pericarditis accounts for ∼5% of all children who present with chest pain to a paediatric
emergency department.
223
Children may be affected by the same syndromes that affect adults.
17
Diagnostic criteria are the same and the risk of recurrence is similar (15–30%). The
aetiology is similar to that in adults, with PPS more often described, particularly
after interatrial defect correction.
18
Compared with adults, children often have a marked inflammatory clinical pattern,
with more commonly fever, pleuropulmonary involvement and raised CRP and less commonly
anti-nuclear antibody (ANA) positivity. This might imply activation of inflammatory
pathways with release of IL-1.
19
No RCT has been done in children. NSAIDs remain the mainstay, at high dosages (
Web Table 7
). Most paediatricians avoid aspirin in children. Colchicine halved recurrences in
children.
19
Corticosteroid use should be restricted in children even more than in adults, given
that their side effects (striae rubre and growth impairment) are particularly deleterious
in growing children; the minimal effective dose should be sought. Severe physical
restriction is bothersome in children and may further worsen their quality of life
and that of their family. Anakinra (anti-IL-1 receptor) is a new option for children,
especially if they are corticosteroid-dependent.
20–23
The long-term prognosis in children is good; however, quality of life can be severely
affected with repeated recurrences, glucocorticoid dependence and severe physical
restriction.
19
Recommendations for therapy of acute and recurrent pericarditis in children
IL = interleukin; NSAIDs = non-steroidal anti-inflammatory drugs.
aClass of recommendation.
bLevel of evidence.
cReference(s) supporting recommendations.
6.2
Pregnancy, lactation and reproductive issues
The most common form of pericardial involvement in pregnancy is hydropericardium,
usually as a benign mild effusion by the third trimester, which is found in up to
40% of women, often occasionally. The effusion is usually silent and clinical examination
and ECG are generally normal. In a few cases, slightly elevated blood pressure and/or
aspecific ST-T changes have been documented.
24,25
The most common disease to require medical therapy is acute pericarditis; diagnosis
is made using the usual criteria. No specific aetiology is usually identified. Nowadays
the general outcomes of pregnancies in these women when followed by dedicated multidisciplinary
teams are similar to those expected in the general population.
25
A proposed treatment scheme for pericarditis during pregnancy is described in
Web Table 8
.
25–27
Pregnancy in women with recurrent pericarditis should be planned during a phase of
disease quiescence.
25–27
Classic NSAIDs (ibuprofen, indomethacin) may be considered during the first and second
trimesters;
25–27
most experts prefer high-dose aspirin, since it is regularly used in anti-phospholipid
syndrome in pregnancy and is moderately effective in the prevention of pre-eclampsia
in high-risk obstetric patients.
224,225
After gestational week 20, all NSAIDs (except aspirin ≤100 mg/day) can cause constriction
of the ductus arteriosus and impair foetal renal function, and they should be withdrawn
in any case at gestational week 32.
224,225
The lowest effective doses of prednisone may be used throughout pregnancy and breastfeeding
(with supplementation with calcium and vitamin D).
25–27
Paracetamol is allowed throughout pregnancy and breastfeeding, as are anti-histamine
H2 blockers or proton pump inhibitors.
226
During pregnancy, tapering of therapies should be extremely cautious. Normal vaginal
delivery is possible and should be considered in the absence of contraindications.
25–27
Ibuprofen, indomethacin, naproxen and prednisone may be considered in women who are
breastfeeding. After discontinuation of breastfeeding, gradual tapering of prednisone
should be considered, eventually resuming colchicine. Colchicine is considered contraindicated
during pregnancy and breastfeeding, even though no adverse events during pregnancy
and foetal or child development have been reported in women with FMF treated with
colchicine during pregnancy and breastfeeding.
227–229
6.3
The elderly
Most guidelines have not discussed the applicability of their recommendations to older
patients with multiple co-morbidities.
230
No paper has specifically addressed pericardial diseases in the elderly, so only expert
opinion exists. Therapy adherence and compliance may be problematic in the elderly
because of cognitive impairment, poor vision or hearing and cost, but the strongest
predictor of non-adherence is the number of medications.
230
Indomethacin is not indicated, the colchicine dose should be halved and particular
care should be taken to evaluate renal impairment and drug interactions.
7.
Interventional techniques and surgery
The aetiology of pericardial diseases remains unresolved in many cases because the
full spectrum of diagnostic methods is not used in many institutions. The gold standard
remains surgical by the subxiphoid approach, allowing collection of fluid samples
and performing pericardial biopsy and pericardial drainage. Interventional techniques
206
include the combined use of imaging by pericardioscopy first described in combination
with diagnostic molecular, histological and immunohistological methods to assess the
aetiology and pathogenesis of pericardial and epicardial disease manifestations
133
and the option to intervene therapeutically by instillation of drugs into the pericardial
sac.
63,204
7.1
Pericardiocentesis and pericardial drainage
For pericardial drainage and biopsy, the surgical approach remains the gold standard.
The classical approach is by subxiphoid incision, through which it is easy to take
fluid samples and perform a pericardial biopsy. The operation is completed by leaving
a small drain in place to evacuate remaining effusion. This technique using a subxiphoid
approach is straightforward for a thoracic or cardiovascular surgeon, if such a team
is close to the cardiology team. In clinical practice, pericardial fluid is aspirated
by pericardiocentesis.
State-of-the-art pericardiocentesis must be guided either by fluoroscopy or echocardiography
206
under local anaesthesia. Blind procedures must be not be used to avoid the risk of
laceration of the heart or other organs, except in very rare situations that are immediately
life threatening. An experienced operator and staff should perform pericardiocentesis
in a facility equipped for radiographic, echocardiographic, haemodynamic and ECG monitoring.
For echo-guided pericardiocentesis, the ideal entry site is the point on the body
surface where the effusion is closest to the transducer and the fluid collection is
maximal. The needle trajectory is defined by the angulation of the handheld transducer
and should avoid vital structures such as the liver, myocardium, lung, internal mammary
artery (3–5 cm away from the parasternal border) and the vascular bundle at the inferior
margin of each rib. The intended point of entry is marked on the skin and the direction
of the ultrasound beam is carefully noted (see Web supplemental material). An additional
technique is the echo-guided approach followed by echo-monitoring of the procedure.
For fluoroscopic-guided pericardiocentesis, a polytef-sheathed needle with an attached
saline-filled syringe is advanced under moderate suction until the pericardial sac
is reached.
206
When using the more common subxiphoid route for pericardiocentesis, a Tuohy-17, blunt-tip
introducer needle is advanced to the left shoulder at a 30-degree angle to the skin,
thus avoiding coronary, pericardial and internal mammary arteries. The lateral angiographic
view provides the best visualization of the puncturing needle and its relation to
the diaphragm and pericardium. The needle is slowly advanced towards the heart shadow
and the epicardial halo phenomenon, under moderate suction and with injection of small
amounts of diluted contrast medium, until pericardial fluid is aspirated. If haemorrhagic
fluid is freely aspirated, a few millilitres of contrast medium may be injected under
fluoroscopic control to verify the position of the needle. A soft J-tip guidewire
is then introduced and after dilatation is exchanged for a multihole pigtail catheter,
through which the fluid is evacuated under the control of intrapericardial pressure.
206
Pericardiocentesis should be performed by experienced operators and carries a risk
of complications ranging from 4 to 10% depending on the type of monitoring, the skill
of the operator and the setting (emergency vs. urgent vs. elective).
183,206
Most common complications include arrhythmias, coronary artery or cardiac chamber
puncture, haemothorax, pneumothorax, pneumopericardium and hepatic injury (
Web Table 9
).
Pericardiocentesis may have additional limitations/dangers when pericardial fluid
is not free and when located in a lateral or posterior position or <10 mm. In these
cases a surgical approach might be safer, depending on local expertise and availability.
7.2
Pericardioscopy
Pericardioscopy permits visualization of the pericardial sac with its epicardial and
pericardial layers. Macroscopic views show a clustering of protrusions, haemorrhagic
areas and neovascularization in malignant pericardial effusion, which are often haemorrhagic,
in contrast to radiogenic or viral and autoimmune effusions.
133,206
Pericardioscopy enables the performing physician to take targeted biopsy specimens
from epicardial and pericardial layers, avoiding epicardial vessels and increasing
the probability of obtaining disease-specific results. For safety reasons it is important
to have a second wire in place. The safety wire allows a quick exchange with a pigtail
catheter and allows autotransfusion in the case of relevant bleeding. By selecting
the biopsy site, less informative white areas of fibrin can be avoided and dark spots
of inflammation, malignancy or haemorrhagic imbibitions can be selected, which can
be identified best in the blue-light mode. Pericardial biopsy can even be taken under
radiologic control alone. The open jaws of the bioptome are advanced gently until
the silhouette of the pericardial sac is reached. Then the jaws are closed and the
biopsy sample is taken. Seven to 10 samples should be taken to reduce sampling error.
The most meaningful diagnostic yield from pericardial biopsies can be obtained by
multiple pericardioscopically guided tissue acquisitions.
This technique is quite demanding and can be performed in only a limited number of
experienced tertiary referral centres. Pericardioscopy may be considered as a diagnostic
method for inspection of the pericardium and epicardium in experienced centres. It
permits safe tissue acquisition in pericardial diseases of unknown origin.
7.3
Pericardial fluid analysis, pericardial and epicardial biopsy
Serosanguinous or haemorrhagic fluid can be found in malignant as well as post-pericardiotomy,
rheumatologic and traumatic effusions or can be caused by iatrogenic lesions during
pericardiocentesis, but also in idiopathic and viral forms. In cases of sepsis, TB
or in HIV-positive patients, bacterial cultures can be diagnostic. Fluid cytology
can separate malignant from non-malignant effusions, which is important for effusions
in tumour patients after radiotherapy of the mediastinum. Discriminative signatures
between malignant and autoreactive effusions are higher levels of tumour markers in
neoplastic pericardial effusion.
133,206
Cytology and assessment of bacterial cultures of the fluid, histological/immunohistological
evaluation of biopsy specimens and molecular analysis (PCR for microbial agents of
fluid and tissue) allow a definite aetiological diagnosis in many cases, which permits
further treatment.
133
7.4
Intrapericardial treatment
In patients with a larger effusion of unknown origin, prolonged pericardial drainage
may allow subsequent intrapericardial treatment.
In neoplastic pericardial effusion, most frequently due to bronchus carcinoma or breast
cancer, intrapericardial cisplatin or thiotepa therapy have been proposed in combination
with systemic antineoplastic treatment, which should be tailored in collaboration
with the oncologist.
204
In autoreactive and lymphocytic pericardial effusion disease-specific intrapericardial
crystalloid triamcinolone (300 mg/m2 body surface) may be considered.
64
Viral pericarditis may be excluded by PCR in fluid and tissue specimens, but such
investigations are not usually performed in uncomplicated cases in clinical practice.
In cases of uraemic pericardial effusion, intrapericardial therapy with triamcinolone
may be considered, apart from intensified haemo- or peritoneal dialysis and fluid
evacuation.
64,65
In rare cases of recurrent effusion, balloon pericardiotomy is an option that allows
a (transient) pericardio(-pleural-)abdominal window for drainage. This approach should
be avoided in neoplastic or purulent effusions.
7.5
Pericardial access for electrophysiology
First reported in 1996,
231
pericardial access has been used for the mapping and ablation of epicardial substrates
of ventricular tachyarrhythmias with improved success rates and avoidance of a surgical
procedure
232,233
(see supplemental Web material and
Web Table 9
for complications of the procedure).
7.6
Surgery for pericardial diseases
7.6.1
Pericardial window
A pericardial window is a cardiac surgical procedure to create a communication, or
‘window’, from the pericardial space to the pleural cavity. The purpose of the window
is to allow a pericardial effusion (usually malignant) to drain from the space surrounding
the heart into the chest cavity in order to prevent a large pericardial effusion and
cardiac tamponade.
The window is usually performed by a cardiac surgeon, but a pericardial window may
be created by video-assisted thoracoscopy or balloon pericardiotomy by a percutaneous
intervention. The main indication is represented by recurrent large effusions or cardiac
tamponade when a more complex operation such pericardiectomy is a high risk or the
life expectancy of the patient is reduced (e.g. neoplastic pericardial disease) and
the intervention is palliative. The results of a pericardial window are less definitive
since the communication may close and recurrent effusions, especially loculated, are
common and may require additional interventions compared with pericardiectomy, which
is a more complex but complete operation.
105
7.6.2
Pericardiectomy
In constrictive pericarditis the treatment is pericardectomy. The decortications should
remove as much of the pericardium as possible with all constricting parietal and epicardial
layers,
103–105
but taking care of perserving the phrenic nerves bilaterally. Only by using sternotomy
can all the constricting pericardial layers be removed. Therefore, left anterolateral
thoracotomy should be avoided since it permits only a partial resection.
It is also necessary to liberate all of the right atrium, the superior vena cava and
especially the inferior vena cava and the inferior part of the right ventricle adjacent
to the diaphragm as far as possible.
103–105
Only when the constricting peel is adherent and calcified is it necessary to leave
behind a few islands of the pericardium. To avoid bleeding, cardiopulmonary bypass
should be employed only in cases of co-existent cardiac surgical lesions, but cardiopulmonary
bypass may be needed in stand-by, in case of the occurrence of haemorrhagic lesions
during the procedure. By applying these principles, the controversy over the type
of operation (complete or radical or only anterior pericardiectomy) is not an issue.
In recurrent constrictive pericarditis, a repeated operation has to be done as soon
as possible, ideally during the first postoperative year. Rare patients with relapsing
pericarditis can also benefit from pericardiectomy.
33
8.
Perspective and unmet needs
Despite a large amount of new data and the first clinical trials that allow clinical
management to be on the road to evidence-based medicine, there are several issues
that require additional research and clarification. The main issues and unsolved questions
include
ngoing basic and clinical research is warranted and needed to address all these issues
and provide additional diagnostic and therapeutic tools for individualized management
of each patient and to improve the prognosis.
Pathophysiology and risk factors for recurrent pericarditis. What is really ‘idiopathic
recurrent pericarditis’?
How is it possible to prevent pericarditis beyond colchicine?
Is drug tapering useful for patients with pericarditis?
What is the best treatment duration for patients with pericardial diseases?
New and individualized therapies for refractory recurrent pericarditis. Are they really
available and useful?
Is exercise restriction really needed for patients with acute and recurrent pericarditis?
Given the high risk of constrictive pericarditis in infective pericarditis (i.e. tuberculous
and purulent) and the promising effect of intrapericardial fibrinolysis in case reports
and small trials, is intrapericardial fibrinolysis in exudative pericarditis really
safe and efficacious? And when should it be considered in the clinical management
of patients?
What interventions are required to reduce the high mortality of tuberculous pericarditis
treated with antituberculosis medication?
What actually is pericarditis with myocarditis?
What are the long-term outcomes of patients with myopericarditis and perimyocarditis?
Aetiology and pathophysiology of isolated pericardial effusion. What is ‘idiopathic
pericardial effusion’?
Is diagnosis and treatment necessary for all moderate to large pericardial effusions?
What are the indications for invasive diagnostic techniques and their diagnostic yield
in clinical practice?
What is the role, value and application of intrapericardial therapies?
Is pericardiectomy really useful and indicated in refractory recurrent pericarditis?
What are the causes and risk factors for constrictive pericarditis?
What is the best timing for surgical therapies in pericardial diseases?
9.
To do and not to do messages from the pericardium guidelines
CMR = cardiac magnetic resonance; CRP = C-reactive protein; CT = computed tomography;
ECG = electrocardiogram; ESR = erythrocyte sedimentation rate; NSAID = non-steroidal
anti-inflammatory drug; TB = tuberculosis; WBC = white blood cell.
*High risk when there is at least one risk factor among the following: high fever
(>38°C), subacute course without a clear-cut acute onset, large pericardial effusion
(i.e. diastolic echo-free space >20 mm), cardiac tamponade, failure to respond to
NSAID therapy, myopericarditis, immunodepression, trauma or oral anticoagulant therapy.
aClass of recommendation.
bLevel of evidence.
10.
Web addenda
All Web figures and Web tables are available in the online addenda at: http://www.escardio.org/Guidelines-&-Education/Clinical-Practice-Guidelines/Pericardial-Diseases-Guidelines-on-the-Diagnosis-and-Management-of
11.
Appendix
ESC Committee for Practice Guidelines (CPG): Jose Luis Zamorano (Chairperson) (Spain),
Victor Aboyans (France), Stephan Achenbach (Germany), Stefan Agewall (Norway), Lina
Badimon (Spain), Gonzalo Barón-Esquivias (Spain), Helmut Baumgartner (Germany), Jeroen
J. Bax (The Netherlands), Héctor Bueno (Spain), Scipione Carerj (Italy), Veronica
Dean (France), Çetin Erol (Turkey), Donna Fitzimons (UK), Oliver Gaemperli (Switzerland),
Paulus Kirchhof (UK/Germany), Philippe Kolh (Belgium), Patrizio Lancellotti (Belgium),
Gregory Y.H. Lip (UK), Petros Nihoyannopoulos (UK), Massimo F. Piepoli (Italy), Piotr
Ponikowski (Poland), Marco Roffi (Switzerland), Adam Torbicki (Poland), Antonio Vaz
Carneiro (Portugal), Stephan Windecker (Switzerland).
ESC National Cardiac Societies actively involved in the review process of the 2015
ESC Guidelines on the diagnosis and management of pericardial diseases:
Albania: Albanian Society of Cardiology, Naltin Shuka; Armenia: Armenian Cardiologists
Association, Hamayak Sisakian; Austria: Austrian Society of Cardiology, Julia Mascherbauer;
Azerbaijan: Azerbaijan Society of Cardiology, Elnur Isayev; Belarus: Belarusian Scientific
Society of Cardiologists, Vadim Shumavets; Belgium: Belgian Society of Cardiology,
Guy Van Camp; Bulgaria: Bulgarian Society of Cardiology, Plamen Gatzov; Croatia: Croatian
Cardiac Society, Jadranka Separovic Hanzevacki; Cyprus: Cyprus Society of Cardiology,
Hera Heracleous Moustra; Czech Republic: Czech Society of Cardiology, Ales Linhart;
Denmark: Danish Society of Cardiology, Jacob Eifer Møller; Egypt: Egyptian Society
of Cardiology, Mohamed Wafaie Aboleineen; Estonia: Estonian Society of Cardiology,
Pentti Põder; Finland: Finnish Cardiac Society, Jukka Lehtonen; Former Yugoslav Republic
of Macedonia: Macedonian Society of Cardiology, Slobodan Antov; France: French Society
of Cardiology, Thibaud Damy; Germany: German Cardiac Society, Bernhard Schieffer;
Greece: Hellenic Cardiological Society, Kyriakos Dimitriadis; Hungary: Hungarian Society
of Cardiology, Robert Gabor Kiss; Iceland: Icelandic Society of Cardiology, Arnar
Rafnsson; Israel: Israel Heart Society, Michael Arad; Italy: Italian Federation of
Cardiology, Salvatore Novo; Kyrgyzstan: Kyrgyz Society of Cardiology, Erkin Mirrakhimov;
Latvia: Latvian Society of Cardiology, Pēteris Stradiņš; Lithuania: Lithuanian Society
of Cardiology, Ausra Kavoliuniene; Luxembourg: Luxembourg Society of Cardiology, Andrei
Codreanu; Malta: Maltese Cardiac Society, Philip Dingli ; Moldova: Moldavian Society
of Cardiology, Eleonora Vataman; Morocco: Moroccan Society of Cardiology, Mustapaha
El Hattaoui; Norway: Norwegian Society of Cardiology, Stein Olav Samstad; Poland:
Polish Cardiac Society, Piotr Hoffman; Portugal: Portuguese Society of Cardiology,
Luís Rocha Lopes; Romania: Romanian Society of Cardiology, Doina Ruxandra Dimulescu;
Russia: Russian Society of Cardiology, Grigory P Arutyunov; Serbia: Cardiology Society
of Serbia, Milan Pavlovic; Slovakia: Slovak Society of Cardiology, Juraj Dúbrava;
Spain: Spanish Society of Cardiology, Jaume Sagristà Sauleda; Sweden: Swedish Society
of Cardiology, Bert Andersson; Switzerland: Swiss Society of Cardiology, Hajo Müller;
The Netherlands: Netherlands Society of Cardiology, Berto J. Bouma; Turkey: Turkish
Society of Cardiology, Adnan Abaci ; UK: British Cardiovascular Society, Andrew Archbold;
Ukraine: Ukrainian Association of Cardiology, Elena Nesukay.
†Affiliation: Massimo Imazio, Coordinator, Cardiology Department, Maria Vittoria Hospital
and Department of Public Health and Pediatrics, University of Torino, Torino, Italy.
Email: massimo.imazio@unito.it
The CME text ‘2015 ESC Guidelines on the diagnosis and management of pericardial diseases’
is accredited by the European Board for Accreditation in Cardiology (EBAC). EBAC works
according to the quality standards of the European Accreditation Council for Continuing
Medical Education (EACCME), which is an institution of the European Union of Medical
Specialists (UEMS). In compliance with EBAC/EACCME Guidelines, all authors participating
in this programme have disclosed any potential conflicts of interest that might cause
a bias in the article. The Organizing Committee is responsible for ensuring that all
potential conflicts of interest relevant to the programme are declared to the participants
prior to the CME activities. CME questions for this article are available at: European
Heart Journal http://www.oxforde-learning.com/eurheartj and European Society of Cardiology
http://www.escardio.org/guidelines