Current Cardiology Reports (2022) 24:905–913

https://doi.org/10.1007/s11886-022-01710-8

PERICARDIAL DISEASE (AL KLEIN AND CL JELLIS, SECTION EDITORS)

Acute Pericarditis: Update

Emilia Lazarou1 · Panagiotis Tsioufis1 · Charalambos Vlachopoulos1 · Costas Tsioufis1 · George Lazaros1 

Accepted: 2 May 2022 / Published online: 20 May 2022

© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022

Abstract
Purpose of Review  Since 2015, when ESC guidelines for the diagnosis and management of pericardial diseases were pub-
lished, ongoing research has enhanced the current state of knowledge on acute pericarditis. This review is an update on the
latest developments in this field.
Recent Findings  In recurrent acute pericarditis, autoinflammation has been included among causative mechanisms restricting
the vague diagnoses of “idiopathic” pericarditis. Cardiac magnetic resonance that detects ongoing pericardial inflammation
may guide treatment in difficult-to-treat patients. Development of risk scores may assist identification of patients at high
risk for complicated pericarditis, who should be closely monitored and aggressively treated. Treatment with IL-1 inhibitors
has been proven efficacious in recurrent forms with a good safety profile. Finally, acute pericarditis has recently attracted
great interest as it has been reported among side effects post COVID-19 vaccination and may also complicate SARS-CoV-2
infection.
Summary  Recent advancements in acute pericarditis have contributed to a better understanding of the disease allowing a
tailored to the individual patient approach. However, there are still unsolved questions that require further research.

Keywords  Acute pericarditis · Outcome · Pathophysiology · Novel treatments · Recurrent pericarditis

Abbreviations Introduction
CMR Cardiac magnetic resonance
COVID-19 Coronavirus disease-19 Acute pericarditis is the most common inflammatory heart
CRP C-reactive protein disorder, ahead of acute myocarditis and infective endocardi-
CCT​ Cardiac computed tomography tis [1]. In the Western world, the incidence of acute pericar-
ESC European Society of Cardiology ditis in the general population is estimated at approximately
HIV Human immunodeficiency virus 27.7 cases per 100,000 subjects per year, whereas the stand-
IL-1 Interleukin-1 ardized incidence rate of hospital admissions for pericarditis
IVIG Intravenous immunoglobulin is 3.32 cases per 100,000 person-years [1–3]. Pericarditis,
LGE Late gadolinium enhancement similarly to myocarditis, is more common among younger
NSAIDs Nonsteroidal anti-inflammatory drugs males. Sex hormones, mainly testosterone, appear to play a
PET Positron emission tomography role in the different susceptibility of pericarditis in men and
PPI Proton pump inhibitors women [1, 4].
SARS-CoV-2 Severe acute respiratory syndrome corona- Acute pericarditis is an overall benign and self-limiting
virus 2 disease [1]. However, in some unfortunate instances, com-
plications may occur either in the short term (such as cardiac
tamponade which is a dreadful and potentially life-threatening
complication if not promptly recognized and treated), mid-
This article is part of the Topical Collection on Pericardial Disease term (recurrent pericarditis), or long term (permanent con-
strictive pericarditis) [5]. The incidence of complications
* George Lazaros depends largely on the underlying etiology (higher in sec-
glaz35@hotmail.com ondary forms), certain patient characteristics (age and sex),
1
First Cardiology Department, School of Medicine,
and treatment choice (such as use of glucocorticoids) [1, 4,
Hippokration General Hospital, National and Kapodistrian 6•, 7]. Acute pericarditis may appear either as an isolated
University of Athens, Vas. Sofias 114, 11528 Athens, Greece

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disease or in the context of a systemic disorder. In the latter pericardiocentesis and pericardial biopsy respectively would
circumstance, a multidisciplinary approach is of paramount be possibly able to identify the infectious agent, but this is
importance for a favorable outcome. Indeed, in the so-called an invasive and non-recommended approach for an overall
idiopathic (presumably viral) forms, cardiologists are involved benign disorder [1].
in patient management, whereas in the secondary forms, a col- According to the current guidelines, the routine identifi-
laboration between cardiologists and other medical specialties cation of the causative viral agent, with the possible excep-
is required (e.g., rheumatologists, oncologists) [8]. In contrast tion of hepatitis C virus and HIV, is not recommended, since
to first presenting acute pericarditis, recurrent pericarditis is it does not affect treatment decisions and prognosis [1]. Tak-
a problematic and often difficult to treat condition [9]. After ing into account the above clues, in the contemporary litera-
a first episode of acute pericarditis, the rate of first recurrence ture, the terms viral and idiopathic pericarditis are consid-
is reported at 15–30% of cases [10]. Notably, among patients ered synonyms, assuming that idiopathic is of a presumably
with a first recurrence, a second is observed in 25–50%, and (but not proven) viral etiology [13]. It is stressed that in the
a further (third) in 20–40% [10]. In some unfortunate cases etiology search of acute pericarditis, the local epidemiologi-
(approximately 5–10%), additional recurrences may appear cal data should always be considered. For instance, in the
with detrimental impact on patients’ quality of life, due to developing countries, the most common form of pericarditis
frequent emergency department or hospital admissions as well is tuberculous, which accounts for approximately 70–80%
as complications related to medical treatment [10, 11]. Thus, of cases with the rate increasing to 90% in HIV-positive
the so-called glucocorticoid-dependent, colchicine-resistant patients [7].
recurrent pericarditis is a major challenge for contemporary As already mentioned, the identification of the underlying
cardiology and a field of intense ongoing research regarding etiology is of paramount importance for a tailored treatment
pathophysiology, prompt recognition of these patients, and plan. In this line, the identification of patients who probably
optimal treatment. suffer from pericarditis in the context of a systemic disorder
is strongly recommended. Features suggesting a secondary
(specific) etiology are summarized in Table 2 [1]. Patients
Etiology presenting with at least one of those findings should be hos-
pitalized, monitored for complications (mainly cardiac tam-
The etiology of pericarditis includes infectious and non- ponade), and subjected to an extensive clinically oriented
infectious forms (Table 1) [1, 7]. Among infectious forms, diagnostic work-up, including blood work and second-level
the most common is viral pericarditis which accounts for imaging in order to reveal potential specific etiologies [1].
approximately 80–85% of all pericarditis cases [1, 7]. A Among all comers with acute pericarditis, it is estimated that
recent clinically apparent viral infection (upper respiratory at least 1 high-risk criterion is found in approximately 15%
tract infection or gastroenteritis) has been documented in of total cases [14].
approximately 40% of patients presenting with acute peri- Besides the well-recognized etiologies of acute pericar-
cardial inflammation [12]. At the time of pericarditis diag- ditis, two important new etiologies have been described in
nosis, however, viral infection cannot be confirmed with the last 2 years. The first is infectious, namely SARS-CoV-2,
serology antibody testing since IgM antibodies are often no and the second non-infectious, which is the vaccine against
longer detectable [1]. Molecular techniques (such as poly- COVID-19 and especially the mRNA vaccine platforms [15,
merase chain reaction) on pericardial fluid or tissue after 16•]. With these 2 novel etiologies, pericarditis along with

Table 1  Most common etiology of acute pericarditis

A. Infectious (80–85%) B. Non-infectious (15–20%)

Viral (most common): Autoimmune (up to 10%):

  • Coxsackievirus echovirus   • Post-cardiac injury syndromes
  • Herpes viruses   • Systemic autoimmune and autoinflammatory diseases
  • Influenza Neoplastic pericarditis (5–7%):
  • Adenovirus   • Rarely primary and most often secondary tumors
  • HCV Metabolic:
  • HIV   • Uremia
  • Parvovirus B19 Myxedema
  • SARS-CoV-2, etc Drug related:
Non-viral:   • Antineoplastic drugs
  • Bacterial (Tuberculous 4–5%, Coxiella burnetii)   • Drugs inducing lupus-like syndrome
  • Rarely fungal and parasitic   • Vaccines (including vaccines against COVID-19)

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Table 2  Diagnosis, classification, and high-risk criteria of acute pericarditis

Diagnostic criteria for acute pericarditis High-risk criteria for secondary/complicated pericarditis
(at least 2 out of 4 should be fulfilled) *

  • Pleuritic chest pain   • Fever > 38 °C

  • Pericardial friction rubs   • Subacute symptom onset
  • ECG changes (widespread ST elevation, PR depression among others)   • Large pericardial effusion with or without signs of
  • Pericardial effusion (new appearing or worsening) tamponade
Classification of pericarditis   • Poor response to NSAID aspirin after 1 week of treatment
  • Oral anticoagulant therapy
  • Acute: New-onset
  • Myopericarditis
  • Incessant: Symptoms persisting for more than 4–6 weeks but less than
  • Trauma
3 months
  • Immunosuppression
  • Recurrent: Relapse after a symptom-free period of at least 4–6 weeks
  • Chronic: Symptom duration of more than 3 months

CRP and evidence of pericardial inflammation with second-level imaging are considered supportive findings

myocarditis have taken front stage. In the setting of COVID- of the 4 criteria, which are depicted in Table 2 and Sup-
19 infection, real-world data showed that new-onset peri- plemental Fig. 1 [1]. Among them, the most common is
carditis developed in 1.5% of cases. The 6-month all-cause pleuritic chest pain which typically worsens with inspiration
mortality was 15.5% for patients with pericarditis vs. 6.7% and is relieved in the sitting position and leaning forward.
in matched controls with COVID-19 but without pericar- It is observed in more than approximately 90–95% of cases
ditis [17]. In another large study, the incidence rate ratio [1, 7, 21].
of pericarditis 1–28 days following a SARS-CoV-2 posi- The second is auscultation of pericardial rubs, which
tive test was 2.79 [18••]. Concerning vaccination against although pathognomonic for acute pericarditis, are encoun-
COVID-19 (any vaccine), in the latter study which included tered in approximately 30% of patients. However, it is an
38,615,491 adults that had been vaccinated with at least intermittent finding that requires expertise for its detection
one dose, 0.001% were hospitalized with pericarditis in the [1, 22]. Pericardial effusion is found in 60–80% of cases and
1–28 days after any dose of vaccine [18••]. Similar find- is taken into consideration if first appearing or worsening
ings were recorded in another study including 2,000,287 during the course of the disease [1, 14, 23]. In most cases
individuals receiving at least 1 vaccination dose [19]. Peri- (~ 80%), the effusion is small-sized, less often moderate
carditis developed in 37 cases, most often (~ 60%) after the (10%) or large (10%) with or without evidence of cardiac
second immunization with a median onset of 20 days (IQR, tamponade [14]. It should be emphasized that the size of
6.0–41.0 days) after the most recent vaccination. Notably, in the effusion is calculated semi-quantitatively with transtho-
contrast to acute myocarditis, pericarditis was more common racic echocardiography by measuring the largest diameter of
in older subjects [19]. The above data provide indisputable the effusion in end-diastole [1]. The effusion appears as an
evidence that benefits of COVID-19 vaccination counter- echo-free space between the visceral and parietal pericardial
balance any concerns about the possible but definitely rare layers and is considered small if the space in question is
vaccine-induced pericarditis and inflammatory heart disease less than 1 cm, moderate if between 1 and 2 cm, and large if
overall. greater than 2 cm [1]. Quantitative assessment of pericardial
In our institutional experience stemming from a referral fluid is obtained with computed tomography with a specific
center for pericardial diseases in a large urban area, the over- software, and CMR [1].
all clinical course in subjects presenting with pericarditis Electrocardiography is a valuable tool for the diagnosis
following COVID-19 vaccination does not differ compared of acute pericarditis and a differential diagnosis of alter-
to common viral pericarditis [20]. native etiologies of chest pain. Classically, 4 phases of
approximately 1 week each are described. However, the
duration of each phase varies largely between patients
Diagnosis and depends on the time of starting medical treatment,
its effectiveness, and eventual appearance of complica-
In the absence of a specific biomarker, such as troponins tions [1, 21]. Typical findings include diffuse concave
for myocardial necrosis, the diagnosis of acute pericarditis ST segment elevation without coronary artery territorial
(either first episode or recurrences) is based on clinical and distribution, PR segment depression (which is the most
imaging findings. According to the 2015 ESC guidelines specific finding in acute pericarditis), no reciprocal ST
for the diagnosis and management of pericardial diseases, segment depression, ST segment depression in lead aVR
the diagnosis is established by the presence of at least 2 out and occasionally in V1 lead, and notably, lack of Q wave

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Fig. 1  Treatment principles for recurrent acute pericarditis

development. In the second phase, the ST and PR seg- electrocardiogram, rendering the diagnosis of pericarditis
ments become isoelectric, in the third T wave, inversion challenging with the adoption of the established criteria [4].
is observed, and in the last phase, the electrocardiogram
normalizes (the latter phase in some instances may appear
later on). Unfortunately, this typical series of events is Diagnostic Work‑up
observed in 50–60% of cases and in several patients, the
electrocardiogram depicts non-specific findings [1, 21, In a patient with a suspected first episode of acute pericar-
22]. ditis, routine (or first-level investigations) diagnostic work-
Apart from the aforementioned criteria, additional less up according to the ESC guidelines should include detailed
specific symptoms may be encountered in the individual medical history, physical examination with emphasis on
patient such as fever, cough, and dyspnea along with other heart auscultation, chest X-ray, electrocardiogram, echo-
findings suggesting eventually a secondary form such as cardiography, and routine blood tests which should include
arthritis, rush, and lymph node enlargement. According to markers of inflammation (mainly CRP), troponin, and thy-
the ESC guidelines, inflammatory markers and evidence roid hormones [1]. In the presence of one or more high-risk
of myocardial inflammation by an imaging modality (CT, criteria, a more extensive work-up should be considered due
CMR) are considered supportive findings and at present to the higher prevalence of a secondary condition in these
are not included among the main diagnostic criteria [1]. patients [1]. The same holds true for patients with recurrent
For CMR, the main reason for exclusion is the limited acute pericarditis where secondary conditions are more prev-
availability and cost. Regarding C-reactive protein, apart alent as well [5]. When a secondary condition is suspected,
from its low specificity (as it elevates in inflammatory con- then a broader blood work should be performed including
ditions of any etiology), another concern is that in approxi- serologic markers for autoimmune diseases, thyroid hor-
mately 22% of cases, it is found within normal limits at mones, QuantiFERON-TB Gold, and tumor markers. CCT
the time of presentation [24]. This is due to CRP synthesis or cardiac MRI are also included among the second-level
rate kinetics, as CRP levels start rising beyond normal investigations and should be adopted when routine (first
values approximately 6 h after inflammation onset. How- level) testing is not sufficient for diagnostic purposes [1].
ever, CRP values have been found to be elevated in 96% CCT offers the advantage of superior spatial resolution.
of patients with acute pericarditis if measured at least 12 h It is the most accurate imaging technique for the measure-
after symptom onset [25]. ment of pericardial thickness and the evaluation of pericar-
Finally in assessing a patient with suspected acute peri- dial calcifications (in terms of presence and burden) which is
carditis, age and sex peculiarities should be considered. For particularly helpful in planning surgical pericardiectomy. In
instance, it has been shown that elderly females with acute contrast, it is not indicated in the evaluation of inflammatory
pericarditis may present with dyspnea rather than chest pain, pericardial conditions [26]. Cardiac MRI with its ability of
without rubs and fever and with non-specific findings in the tissue characterization, apart from diagnostic clues, offers

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invaluable information concerning treatment guidance [10, arteriography was performed in ~ 17% of patients which
26, 27••]. Actually, depending on the presence of pericardial were finally diagnosed with acute pericarditis [29]. The rel-
edema in the T2 sequences and late gadolinium enhance- evant rate in those presenting with ST segment elevation
ment, the stage of disease and the effectiveness of treatment was ~ 25%. This rate dictates the diagnostic challenges in
are evaluated, especially in cases of recurrent disease. In suspected acute pericarditis in the everyday clinical practice
specific, during the acute phase of pericarditis, both edema [29].
and LGE are observed. Resolution of edema with LGE per- Patients with a clinical picture of acute pericarditis with
sistence dictates a subacute/chronic phase of the disease, elevated troponin levels but without impairment of left ven-
whereas the absence of both edema and LGE dictates heal- tricular ejection fraction nor left ventricular wall motion
ing [1, 10, 26, 27••]. Cardiac MRI is also a valuable tool abnormalities are being diagnosed with myopericarditis [1,
in the assessment of effusive-constrictive pericarditis, an 7]. On the other hand, patients with pleuritic chest pain,
uncommon disorder identified by pericardial effusion caus- with or without pericardial effusion, but with evidence of
ing tamponade combined with thickened visceral pericar- left or biventricular function abnormalities, are diagnosed
dium causing constriction, which is typically unveiled upon with perimyocarditis and are managed in a similar way to
pericardial drainage. The presence of pericardial edema and pure myocarditis patients [7]. The subgroup of myoperi-
LDH as depicted by MRI suggest a possible reversibility of carditis patients is treated in the same way as “pure” acute
the condition with anti-inflammatory treatment [1, 26]. pericarditis. However, according to the ESC guidelines, the
In an individualized fashion, tumor markers, PET-CT, lower effective dose of NSAIDs for the shorter possible
and pericardial biopsy may be performed [1]. It should be period should be administered since it has been shown in
mentioned that “idiopathic” pericarditis is not a life-long animal models that NSAIDs may enhance inflammation and
diagnosis and difficult-to-treat patients with multiple recur- increase mortality [1]. Moreover, the currently available data
rences should be periodically reassessed to exclude the to recommend the use of colchicine in this setting are insuf-
development of a secondary condition. In this subgroup of ficient [1]. From a clinical perspective, the latter patients
patients, it has been shown that in approximately 10% of do not seem to have a worse prognosis compared to the
cases, an occult secondary disorder may emerge, which most acute pericarditis counterpart and interestingly, they depict
often is an autoimmune disorder (such as Sjögren syndrome less often recurrences (11% vs. 32%) after a first episode
and rheumatoid arthritis in a relevant case series) [28]. [30]. However, performing cardiac CMR in myopericarditis
patients is reasonable, in order to assess the presence and
extent of myocardial involvement [1].
Differential Diagnosis

The differential diagnosis encompasses practically all cases Treatment

of acute chest pain, including myocardial ischemia/infarc-
tion, pulmonary embolism, aortic dissection, inflammatory The treatment principles of acute pericarditis are depicted
conditions of the chest (pneumonia), and benign conditions in Fig. 1. Exercise restriction is recommended in the acute
such as gastroesophageal reflux and musculoskeletal pain phase until symptom remission and CRP normalization
[1, 21, 22]. In most cases, based on the first-level investiga- [1]. Return to competitive sports in uncomplicated cases
tions for pericarditis i.e., electrocardiography, chest X-ray, is allowed 3 months after the acute attack and should be
echocardiography, and routine blood work plus CRP and prolonged to 6 months in cases of myopericarditis [1]. The
troponin, it is possible to obtain a correct diagnosis [1]. Nev- time of exercise restriction, especially in cases of recurrent
ertheless, in the individual patient, additional tests may be forms, is a matter of debate and in general, strenuous activity
needed such as D-dimer measurement and chest CT among should be probably even more delayed [31].
others [1]. It is however emphasized that in certain clinical The mainstay for the medical treatment of acute pericar-
scenarios, the exclusion of myocardial infarction is quite ditis includes NSAIDS, colchicine, and proton pump inhib-
challenging. In particular, although the diagnosis of acute itors for gastroprotection. The most commonly employed
pericarditis is rather straightforward in a young male without NSAIDs in clinical practice are ibuprofen (600–800 mg tid),
risk factors for coronary artery disease presenting with chest aspirin (1 g tid), naproxen (500 mg bid), and indomethacin
pain and ST segment elevation, this does not hold always (50 mg tid). Aspirin should be preferred in patients already
true for a middle aged or elderly man with a history (or receiving it for an alternative indication (e.g., coronary or
multiple risk factors) of coronary artery disease presenting peripheral artery disease). Although indomethacin has a
with a similar electrocardiogram. In this specific scenario, consistent anti-inflammatory effect, concerns related to side
the exclusion of coronary artery obstruction with coronary effects (mainly gastrointestinal) limit its use especially in the
arteriography is sometimes mandatory. In a study, coronary elderly and in patients with coronary artery disease. NSAID

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dose tapering, although not supported by high-quality data, pregnancy beyond the 20th week of gestation, systemic
is supported by most experts [1, 7, 21]. According to the inflammatory diseases, and possibly post-cardiac syndromes
current recommendations, the full dose should be given for where they seem more efficacious [1, 7, 21]. Glucocorti-
7–10 days, and tapering should be performed in the follow- coids are extremely effective in providing fast symptom
ing 3–4 weeks in an individualized manner (250–500 mg relief. However, they may favor side effects, and their safety
for aspirin and 200–400 mg for ibuprofen every 1–2 weeks). profile, when administered for long periods, is concerning
Before dose tapering, CRP should normalize; otherwise, the [7]. The recommended dose is 0.2–0.5 mg of prednisone
patient is exposed to a hazard of recurrence (2.98) [24]. In or equivalent dose of an alternative steroid, provided that
cases of recurrent pericarditis, longer duration of NSAID bacterial infections, including tuberculosis, have been ruled
administration is often required [1]. Interestingly in a recent out [1]. After administration of the full dose until symptom
study, beta-blockers on top of standard anti-inflammatory resolution and CRP normalization (usually after 1–2 weeks),
therapies have been associated with improved symptom dose tapering should be performed depending on the start-
control through lowering of the heart rate and consequently ing dose, according to the ESC guideline recommendations
friction between the pericardial layers [32]. [1]. Notably, very slow decrements should be performed in
Colchicine has been established as the backbone medica- refractory recurrent cases, especially when the dose admin-
tion in the whole spectrum of pericarditis (first episode and istered is close to the threshold of the individual patient for
recurrences) [1, 7, 21, 33]. It is the only medication that recurrence [1]. Supplementation with calcium and vitamin D
definitely affects recurrences, as it has been shown to halve in all cases and bisphosphonates in men and postmenopausal
the rate of first and subsequent relapses. It is administered women are recommended to restore calcium balance and
on top of anti-inflammatory medications (either NSAIDs bone loss, especially when long-term treatments are sup-
or corticosteroids). The recommended dose is 0.5–0.6 mg posed to be given [7].
twice daily [1, 34]. It is a safe medication and the most com- The subgroup of patients with colchicine-resistant
mon adverse effects are gastrointestinal side effects (mainly glucocorticoid-dependent recurrent pericarditis is a field
diarrhea) in up to 10% of cases [1, 7, 21, 34]. Since colchi- of great interest and intense research. This is a very chal-
cine has a narrow therapeutic index, interaction with other lenging population with an average disease duration
medication may be worrying [7, 34, 35]. However, this is of ~ 4.7 years, needing a tailored to the individual patient
fairly unusual at the doses recommended for pericarditis. In treatment plan, according to the clinical phenotype [28,
patients aged > 70 years and those weighing < 70 kg, starting 37•]. A detailed report on this subgroup is out of the scope
with half dose should be considered, in order to avoid side of this short update. In brief, treatment options include tri-
effects leading to drug discontinuation [1, 34]. Moreover, ple therapy with NSAIDs, colchicine, and glucocorticoids
dose adjustments should be performed in chronic renal dis- [36]. NSAIDs are usually added when relapses appear dur-
ease in relation to creatinine clearance and hepatic function ing the tapering process of glucocorticoids, in an effort to
[1]. Colchicine should be administered for 3 months in a break the vicious circle of steroid dependency [1, 36]. Other
first episode of acute pericarditis, and for at least 6 months options include immunomodulatory, immunosuppressant,
in recurrent forms. Longer periods of administration should and biological drugs including intravenous human immu-
be individually considered in refractory cases [1]. Colchi- noglobulins, azathioprine, hydroxychloroquine, anakinra,
cine at present is not recommended as monotherapy in any and rilonacept [1, 38, 39]. However, solid high-quality
pericardial syndrome and does not seem to be beneficial in data are available for the latter two biological agents [40,
the absence of overt inflammation, namely with normal CRP 41, 42••, 43•]. The rationale for the introduction of anak-
[1, 33]. According to a recent investigation, its usefulness inra and rilonacept in refractory pericarditis treatment is
with respect to recurrences has been questioned in low-risk the emerging concept that recurrent pericarditis (or a list
cases (patients with a first episode not receiving glucocor- of a proportion of cases) belongs to the broader family of
ticoids), but this is not enough to change the established autoinflammatory disorders such as familial Mediterranean
practice of administering colchicine in all comers with acute fever [37•, 44]. In these disorders, an abnormal activation of
pericarditis [35]. the innate immune system and IL-1 displays a central role
In pericarditis treatment algorithm, glucocorticoids in disease manifestations [44]. Both anakinra and rilona-
constitute a second-line treatment option [1, 36]. They cept inhibit IL-1α and β, and have been proven extremely
are administered in cases of true allergy or intolerance to efficacious in refractory pericarditis, achieving a rapid and
NSAIDs, recent gastrointestinal ulcer, concomitant antico- sustained disease remissions with a good safety profile [40,
agulant therapy with high risk of bleeding, chronic renal 41, 42••, 43•]. IL-1 inhibition is particularly recommended
disease (NSAIDs are contraindicated in cases with creati- in cases characterized by a high inflammatory burden, as
nine clearance below 30 ml/min and should be administered disclosed by CRP elevation and fever at each recurrence
with caution when clearance is between 30 and 50 ml/min), [37•]. In contrast, in case of a non-inflammatory phenotype,

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especially if the presence of an autoimmune disease, intra- includes 6 variables independently associated with relapses,
venous immunoglobulins and azathioprine may be benefi- namely age, platelet count, and effusion size as negative pre-
cial [22, 37•]. An issue that needs particular attention is dictors and in-hospital use of corticosteroids, heart rate, and
that although IL-1 inhibition is an important innovation in reduced inferior vena cava collapse as positive predictors. In
the treatment of recurrent pericarditis, further relapses may patients with low score, the observed rate of recurrences was
appear after discontinuation of treatment [45]. Finally, as 21.3%, whereas in those with high score, the relevant rate
a last resort in cases of recurrent pericarditis refractory to was 69.8%. A second risk score (Torino Risk Score) has been
treatment, or in those in which treatment cannot be tolerated also recently presented as a risk stratification tool to predict
due to side effects, pericardiectomy should be performed in complicated pericarditis in patients with a first of subsequent
experienced referral centers [1]. episodes of acute pericarditis [49].
In the setting of COVID-19, the currently in use medica-
tions for pericarditis (such as colchicine, glucocorticoids,
and anakinra) are acceptable [46]. Concerns about the wors- Conclusions–Perspectives
ening of COVID-19 with NSAIDs are not supported by solid
scientific evidence [46]. Acute pericarditis has gained attention in recent years in
light of novel data regarding pathophysiological issues
and the novel treatments especially for refractory cases.
Prognosis The COVID-19 pandemic further enhanced the public and
media attention on pericardial syndromes, since pericarditis
The prognosis of acute pericarditis largely depends on the is a potential complication appearing either in the setting of
underlying etiology [1]. It is excellent in cases of idiopathic COVID-19 or as a complication after vaccination against
pericarditis, whereas it is ominous in cases of malignant COVID-19, which may affect confidence in vaccination.
involvement of the pericardium (either in the form of pri- Despite the big steps forward in understanding and, sub-
mary or metastatic tumor) [1, 7]. In a Finnish registry, the sequently, treating acute pericarditis, there is still room for
mortality rate in patients hospitalized with acute pericarditis further research. Towards this scope, the recent availability
was 1.1% [3]. Complications recorded after a first episode of of animal models for pericarditis is of paramount importance
acute pericarditis in an Italian study with 60-month follow-up for the decodification of recurrent pericarditis and possibly
include cardiac tamponade (1.2%), constrictive pericarditis the identification of patients prone to recurrences, which is
(0.48%), and recurrent pericarditis (25%). The relevant rates a major challenge in the field of pericarditis. In recent years,
reported in secondary forms are 20.2% (a rate mainly driven drugs that target the pathophysiology have been developed
by neoplastic pericarditis), 8.3%, and 57.1% respectively such as colchicine, an inhibitor of NLRP3 inflammasome
[5]. Notably, incessant pericarditis has been recently associ- formation and anti-IL-1 medications [50, 51]. In this line,
ated with constrictive pericarditis [11]. Arrhythmias, most additional medications able to achieve long-standing and
often atrial fibrillation/flutter, develop in 4.3% of cases and definite remissions after discontinuation of treatment are
the decision for chronic anticoagulation should be based on most welcome. Even though the most recent ESC guide-
CHA2DS2-VASc score [47]. As already mentioned, periodi- lines on pericardial syndromes shed more light in the hazy
cal evaluation of the patient is mandatory, especially if new landscape of pericardial syndromes, they are still affected by
symptoms appear, in order to unveil previously unrecognized the high rate of recommendations with level of evidence C
specific causes and adapt medical treatment [28, 48]. (~ 75%) [1]. Thus, additional research is required to provide
A major challenge in the management of acute pericardi- evidence-based data for the optimal management of pericar-
tis is the identification of patients prone to recurrences. An dial syndromes [52].
aggressive treatment of these patients is recommended with
administration of the highest tolerable dose of anti-inflamma- Supplementary Information  The online version contains supplemen-
tary material available at https://d​ oi.o​ rg/1​ 0.1​ 007/s​ 11886-0​ 22-0​ 1710-8.
tory treatment along with colchicine, serial CRP measurement
before dose tapering, and eventually treatment guidance by
CMR as well as recourse to novel therapies such as anti-IL-1
Compliance with Ethical Standards 
agents. Factors reported to be associated with recurrences Conflict of Interest  Dr. Lazaros received a travel grant and advisory
include use of glucocorticoids (especially high doses with fast board compensation from Kiniksa Pharmaceuticals Ltd. The rest of
tapering), lack of colchicine administration, and tapering of the authors declare that they have no conflict of interest relevant to this
anti-inflammatory treatment prior to CRP normalization [6•, manuscript.
10]. Recently, a risk score (0–22 points) predicting recurrence Human and Animal Rights and Informed Consent  This article does not
in patients hospitalized with a first episode of acute pericardi- contain any studies with human or animal subjects performed by any
tis has been developed in our institution [6•]. The risk score of the authors.

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912 Current Cardiology Reports (2022) 24:905–913

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