Imaging-Guided Therapies for Pericardial Diseases

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ª 2019 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER

STATE-OF-THE-ART PAPER

Imaging-Guided Therapies for Pericardial Diseases Michael Chetrit, MD,a,b,* Bo Xu, MD,a,b,* Deborah H. Kwon,a,b Jay Ramchand, MD,a,b Rene E. Rodriguez, MD,d Carmela D. Tan, MD,d Christine L. Jellis, MD,a,b Douglas R Johnston, MD,a,c Rahul D. Renapurkar, MD,a,e Paul C. Cremer, MD,a,b Allan L. Klein, MDa,b

ABSTRACT Frequently, multimodality imaging is indispensable in the care of patients with pericardial disease. With cardiac magnetic resonance imaging, pericardial inflammation can be characterized as acute, subacute, or chronic. This spectrum of inflammation is variably associated with reduced compliance of the pericardium, which may result in constrictive pathophysiology, typically well-defined with echocardiography. This interplay between inflammation and hemodynamics is often optimally characterized with multimodality imaging and has redefined the approach of pericardiologists to diagnose, prognosticate, and tailor individual therapies. (J Am Coll Cardiol Img 2019;-:-–-) © 2019 by the American College of Cardiology Foundation.

W

hen

anti-

simple presentations of pericarditis. Still, in patients

inflammatory medications, acute peri-

treated

with

appropriate

with complicated or constrictive pericarditis (CP),

carditis is associated with a favorable

data have emerged over the past decade supporting

prognosis (1). Mortality in hospitalized patients is

serum inflammatory markers and multimodality

rare (1%) and most often not related to pericarditis

cardiac imaging as essential to better characterize

(2). Yet morbidity may be substantial and is attributed

active systemic and pericardial inflammation. This

to disabling pain, development of recurrent attacks,

improved understanding has redefined the approach

adverse effects from treatment, and progression to

of pericardiologists to diagnose, prognosticate, and,

constrictive pathophysiology (3). Fortunately, in the

most important, tailor individual therapies. Espe-

majority of patients, acute pericarditis resolves. A

cially with novel therapies on the horizon, including

substantial minority, however, progress to incessant,

more targeted biological immunotherapies, the need

chronic, or recurrent disease. In the 2015 guidelines

to understand the various pericardial disease states

for pericardial disease from the European Society of

has increasing management implications. Therefore,

Cardiology, endorsed by the American College of Car-

the aims of this review are to: 1) explore the spectrum

diology (4), inflammatory markers and cardiac imag-

of pericardial diseases; 2) investigate the role of imag-

ing play a primarily adjunctive role in the overall

ing to better understand the stages, progression, and

diagnosis and management, likely appropriate for

resolution of disease; and 3) review the emerging role

From the aCenter for the Diagnosis and Treatment of Pericardial Diseases, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio; bDepartment of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio; cDepartment of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio; dDepartmemt of Cardiovascular Pathology, Cleveland Clinic, Cleveland, Ohio; and the eImaging Institute, Cleveland Clinic, Cleveland, Ohio. *Drs. Chetrit and Xu are joint first authors of this paper. Drs. Cremer and Klein has a research grant from Kiniksa and is part of the steering committee of Kiniksa and SOBI. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received April 30, 2019; revised manuscript received August 1, 2019, accepted August 7, 2019.

ISSN 1936-878X/$36.00

https://doi.org/10.1016/j.jcmg.2019.08.027

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Therapies for Pericardial Conditions

ABBREVIATIONS

of cardiac imaging to guide therapy and

epicardial adipose tissue to further characterize the

AND ACRONYMS

establish overall prognosis.

pericardium.

THE PERICARDIUM

CCT = cardiac gated computed

descriptive

characteristics,

may inform therapeutic decision making.

tomography

CI = confidence interval

Beyond

CMR can identify active inflammation, a feature that

The pericardial sac proper, referred to as the

CMR = cardiac magnetic

parietal pericardium, is a fibrous sac with

resonance

scant vascularization and is composed of 2

THE SPECTRUM OF PERICARDIAL DISEASE

CP = constrictive pericarditis

layers: the fibrosa and the serosa (Figure 1).

PERICARDITIS. The

DHE = delayed

The fibrosa is rich in fibrous tissue and scant

Cardiology guidelines (4) define an acute episode of

elastic lamellae, while the serosa is a single

pericarditis as 1 that meets 2 or more of the following

layer of mesothelial cells lining the parietal

criteria: 1) pericardial chest pain that varies with po-

LV = left ventricular

fibrosa and the epicardial surface of the heart

sition and radiates to the trapezius; 2) a pericardial

PET = positron emission

(5,6). Between these 2 serosal layers is a vir-

friction rub; 3) diffuse ST-segment elevations and PR-

tual space that normally contains up to 50 ml

segment depressions on electrocardiography; and 4)

of serous fluid. Its primary role is to allow the

echocardiographic evidence of a new or worsening

heart to beat freely within this confined

pericardial effusion (4). Isolated episodes of acute

space and to serve as a protective barrier (7). Peri-

pericarditis are often thought to be caused by viral

cardial effusions are usually a transudate and can be

infections or considered idiopathic. Other etiologies

reabsorbed without sequelae. Exudates can occur in

include

the setting of injury and are accompanied by meso-

autoimmune diseases, infectious, and neoplastic

hyperenhancement

HR = hazard ratio

tomography

STIR = short-tau inversion recovery

post-cardiac

current European Society of

injury

syndrome,

systemic

thelial desquamation, extravasation of the neutro-

diseases (11). Episodes that are self-limiting and

phils, and accumulation of fibrinous exudate on both

confined to a maximum of 4 to 6 weeks are consid-

the visceral and parietal surfaces of the pericardium.

ered simple episodes of acute pericarditis. If pericar-

In the early stages, the inflammatory infiltrate is

ditis recurs after a 4- to 6-week period of latency,

composed primarily of neutrophils and fibrinous

recurrence is diagnosed (4). Recurrent pericarditis is

exudate,

the most common complication of pericarditis,

which

transitions

into

predominantly

mononuclear cell infiltrates. These inflammatory in-

affecting nearly 15% to 30% of patients after their first

filtrates promote both the formation of new thin-

episodes (12). In patients who have had a single

walled vessels and extracellular matrix deposition

recurrence, up to 50% will have an additional recur-

along the lining of the visceral and parietal layers,

rence, typically within the first 18 months (12). Epi-

resulting in an overall thickened pericardium (8).

sodes that last beyond 4 to 6 weeks are considered

Initially, there are no firm adhesions between the 2

incessant, and episodes lasting beyond 3 months are

layers, despite the presence of fibrin. As the inflam-

considered chronic (Central Illustration).

matory process continues and healing begins, how-

Admittedly, these distinct time frames are arbi-

ever, there is organization of the fibrin deposits and

trary, and these diagnoses are not necessarily mutu-

further deposition of new connective tissue, resulting

ally exclusive (2). In addition, the typical diagnostic

in fusion between the parietal pericardium and the

criteria are most appropriate for the index episode.

heart, ultimately leading to a fibrosing pericardium

With recurrent pericarditis, patients often present

with varying degrees of calcification (2,9) (Figure 1).

with chest discomfort and no objective evidence of

On the basis of pathological specimens, the

systemic inflammation, which may be related to

normal thickness of the pericardium has been re-

concurrent anti-inflammatory therapy (13). In a

ported to be between 0.5 and 1.0 mm. Despite being

cohort of 275 patients with histories of idiopathic

the first-line imaging modality of choice to interro-

pericarditis, 10% had recurrence of chest pain without

gate the pericardium (10), transthoracic echocardi-

any other

ography cannot reliably visualize the pericardium

Furthermore, in a cohort of 252 consecutive patients

unless

there

is

pronounced

thickness

evidence

of

active

pericarditis

(14).

present

with recurrent pericarditis, just under 50% of those

(>5 mm) or fluid accumulation between the visceral

diagnosed with a recurrence had fewer than 2 clinical

and the parietal layers (7). Cardiac gated computed

features present at the time of presentation (13). Even

tomography (CCT), with its superior spatial resolu-

though recurrent and chronic diseases are considered

tion, can more reliably identify an abnormally

more severe in nature, these aforementioned classi-

thickened pericardium (defined as >2 mm) (7).

fications rarely inform the severity of active inflam-

Finally, cardiac magnetic resonance (CMR) can be

mation. In these clinical contexts, imaging can be

used to manipulate the signal of the surrounding

particularly informative.

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Therapies for Pericardial Conditions

F I G U R E 1 Imaging the Pericardium

Parietal pericardium serosa

Fibrosa

B

A

Mediastinal serosa

C

D

E

F

C

D

C

D

Fibrosis and Fibroplasia Fibrosa

B

A

C

D

Fibrinous exudate

Granulation tissue and neovascularization

Fibrosa

B

A

Dense fibrosis Fibrosa Pericardial adipose tisssue

A

B

Continued on the next page

CP. CP is characterized by a thickened, fibrotic,

interdependence results in progressive right heart

and/or calcified pericardium that limits diastolic

failure (14). Originally, CP was viewed as an irre-

filling and forces one side of the heart to fill at the

versible chronically progressive condition following a

expense

remote period of pericardial inflammation (15).

of

the

other,

and

this

ventricular

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C E N T R A L IL L U ST R A T I O N Spectrum of Pericardial Disease

ONGO

ING IN

FLAM

MATI

ON

Recurrent

Chronic

Burned Out

T2 + DHE +

T2 ± DHE +

T2 – DHE +

T2 – DHE –

Transient

Subacute/ Effusive Constrictive

Chronic

Calcific

MRI

Acute Pericarditis

Pericardiectomy Indicated

Medical Therapy

4

OGY YSIOL H P E CTIV

TRI CONS

TREATMENT

Triple Therapy ± Biologics

DHE+

T2+

T2-

Diuresis

DHE -

Chetrit, M. et al. J Am Coll Cardiol Img. 2019;-(-):-–-.

The use of cardiac magnetic resonance (CMR)–based pericardial characterization demonstrating the continuum of inflammatory pericardial diseases starting from acute inflammation (with or without constrictive physiology) and ending in either burned-out pericarditis or calcific constrictive pericarditis. DHE ¼ delayed hyperenhancement.

However,

pericarditis,

original description regarding the pathophysiology of

constrictive pathophysiology can be classified as

similar

to

categories

for

CP, suggested 2 forms of CP: a fibroelastic form and a

transient, subacute, or chronic (8) (Central Illustration,

fibrotic and calcific form. The fibroelastic form was

Figure 2, Video 1). In 1980, William Hancock, in his

postulated to represent an acute or subacute phase of

F I G U R E 1 Continued

(First row) Normal parietal pericardium. Histological findings: (A,B) (hematoxylin and eosin): dense fibrous tissue with minimal cellularity and occasional vessels is the typical composition of the parietal pericardium. The parietal pericardium has 2 distinct layers: the fibrosa and the serosa. Note the low vascularization of the normal parietal pericardium. Cardiac cardiac magnetic resonance (MRI): T2 short-tau inversion recovery (STIR) (C) and delayed gadolinium (D) sequences showing no pericardial enhancement. (Second row) Organizing pericarditis with abundant fibroplasia. Histological findings: (A,C) (hematoxylin and eosin) and (B,D) (Movat’s pentachrome): fibrosa layer of the parietal pericardium as a distinct band in the lower part of the images (A to D). An intermediate layer of organizing connective tissue thickens the parietal pericardium and shows abundant fibroplasia (B). This stage precedes the organized phase. The uppermost area of the images shows some mononuclear inflammatory infiltrate. Cardiac MRI: T2 STIR (E) and delayed gadolinium (F) sequences showing enhancement of the pericardium signifying acute or active inflammation (arrow). (Third row) Healing pericarditis with abundant neovascularization of the fibrosa layer of the parietal pericardium. Histological findings: (A) (hematoxylin and eosin) and (B) (Movat’s pentachrome): the small vessels in the granulation tissue are accompanied by mononuclear inflammatory cells, mostly lymphocytes and some fibroblasts (A). The Movat’s pentachrome stain highlights the boundary between the fibrosa layer and the new, organizing fibrous tissue (B). Cardiac MRI (C) T2 STIR images showing resolution of the enhancement, while there is persistence of enhancement on delayed gadolinium sequences (D) of the pericardium, signifying a subacute stage of inflammation. (Fourth row) Healed organized fibrous pericarditis. Histology: hematoxylin and eosin (A) and Movat’s pentachrome (B): the fibrosa layer of the parietal pericardium (B) with an additional layer of dense, mostly acellular (A) layer of fibrous tissue without evidence of residual inflammation, fibroplasia, or neovascularization, thus demonstrating thickening of the pericardium by fibrous connective tissue (B). Cardiac MRI (C,D): T2 STIR and delayed gadolinium images showing resolution of the pericardial enhancement, signifying the absence of inflammation. Adapted from Zurick et al. (8); pericardial specimens and MRIs are representative.

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F I G U R E 2 Suggested Flowchart for the Diagnosis and Prognostication of an Episode of Pericardial Inflammation

Acute Pericarditis 1. Pleuritic Chest Pain 2. Pericardial Friction Rub 3. Typical ECG Changes 4. Pericardial Effusion

Clinical Assessment

Echocardiography

Transient

CMR DHE/T2 STIR

Echocardiography

Constrictive Physiology Present

Constrictive Physiology Absent

Chronic

Acute

T2 – DHE –

T2 + DHE +

Eff Cons T2 + DHE +

Cardiac MRI

Chronic Recurrent

T2 ± DHE + Effusion

T2 ± DHE +

T2 – DHE – >3 months

Latency: 6 weeks

A proposed flow diagram demonstrates the integral role of echocardiography and cardiac magnetic resonance (CMR) for the diagnosis and classification of inflammatory pericardial conditions with a focus on pericardial characterization. See Video 1. DHE ¼ delayed hyperenhancement; ECG ¼ electrocardiographic; Eff Cons ¼ effusive constrictive; STIR ¼ short-tau inversion recovery.

constriction with only mild features of constrictive

resolution of the inciting inflammation, via time or

physiology. Conversely, the fibrosed and calcified

anti-inflammatory therapy, constrictive pathophysi-

form of CP occurred in the setting of chronic and

ology subsequently subsides. In a series of 35 patients

persistent pericardial inflammation and resulted in

with this transient type of constriction, Haley et al.

typical findings of constrictive pathophysiology (16)

(15) observed resolution of the constrictive patho-

(Figure 3, Video 2).

physiology over an average of 3 months (interquartile

Similarly, Sagristà-Sauleda et al. (17) affirmed this hypothesis

by

describing

a

transient

form

range: 8 to 112 weeks).

of

Occasionally, patients present with pericardial

constriction that would heal before the development

tamponade, and pericardiocentesis fails to decrease

of chronic CP. Initially, idiopathic and inflammatory

the elevated right atrial pressure (18). This finding has

or infectious cases were identified, suggesting that

been termed “effusive CP” and is best explained by an

active inflammation played a central role in this

acute effusion causing tamponade combined with a

reversible constrictive pathophysiology (17). More

constricting visceral pericardium (18). This rare

specifically, inflammation and edema render the

manifestation, accounting for approximately 1% of

pericardium stiff and poorly compliant, resulting in

patients with pericarditis, has classically been char-

constrictive pathophysiology with 3 phases: an initial

acterized as a transitional state from an acute effusive

phase consisting of a pericardial effusion (indicative

pericarditis to a more chronic CP (19). In a recent se-

of active inflammation), a second phase with reduced

ries by Kim et al. (20), albeit with different diagnostic

effusion and constrictive pathophysiology by echo-

criteria using echocardiography, among 33 patients

cardiography,

of

with effusive CP, all but 2 resolved with or

normalization of hemodynamic status (17). With

without anti-inflammatory medication, suggesting

and

a

third

phase

consisting

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F I G U R E 3 Multimodality Imaging for Constrictive Pericarditis

A

B

C

D

e’ 10 cm/s Septal Lateral

e’ 19 cm/s

E

F

AR AR

D S

D

S Expiration

Inspiration

A 45-year-old woman with a history of tuberculosis and right heart failure. (A) Chest radiograph demonstrating pericardial calcifications (arrow). (B) Axial four-chamber view on cardiac computed tomography demonstrating extensive calcifications along the lateral wall of the left ventricle and the right ventricular free wall (arrows). Pulsed-wave tissue Doppler of the medial (C) and lateral (D) mitral annulus demonstrating “annulus reversus.” (E) Pulsed-wave Doppler sampling of the hepatic veins demonstrating a prominent end diastolic expiratory flow reversal. (F) Global longitudinal strain profile demonstrating a decreased magnitude along the lateral wall and a compensatory increase in the medial segments suggestive of “strain reversus.” See Video 2. D ¼ diastole; S ¼ systole.

that effusive CP is often within the spectrum of

acute inflammation may or may not have an

transient CP. In a more recent perspective regarding

associated pericardial effusion, and this pericardial

effusive CP, Klein and Cremer (21) postulate that

effusion may or may not cause tamponade. Sepa-

effusive CP is simply part of a wider spectrum

rately, the underlying inflammation can in turn

of pericardial disease. Simply, pericarditis with

result in no hemodynamic consequences, transient

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T A B L E 1 Multimodality Imaging for the Diagnosis of Pericardial Diseases

CT Imaging

MRI

Acute pericarditis/ recurrent pericarditis

First line  Normal findings  Pericardial effusion  Tamponade physiology  Constrictive physiology

Echocardiography

Second line  Thickened smooth pericardium  Pericardial effusion  Iodinated contrast enhancement of the visceral and parietal surfaces is suggestive of acute inflammation

Second line  Thickened pericardium  Pericardial thickening on the T1-weighted black-blood sequence  Increased signal on T2-weighted STIR sequences suggests ongoing edema  DHE indicates active inflammation of the pericardium

Pericardial effusion

First line  Echo-free space between the 2 layers of the pericardium  Trivial: Effusion only seen in systole  Small: <1 cm  Moderate: 1–2 cm of pericardial fluid (corresponds to 500 ml)  Large: >2 cm (generally exceeds 700 ml)  Very large: >2.5 cm

Second line  Pericardial effusion  Quantification: ◦ Trivial: Effusion only seen in systole ◦ Small: <1 cm ◦ Moderate: 1–2 cm of pericardial fluid ◦ Large: >2 cm ◦ Very large: >2.5 cm  Qualitative assessment ◦ Transudative effusions have CT attenuation similar to that of water; <10 HU ◦ Attenuation >10 HU suggests an exudate with high protein content ◦ CT attenuations ranging from 20 to 60 HU suggest a purulent, malignant, or myxedematous exudative effusion ◦ Attenuation >60 HU is best correlated with a hemorrhagic effusion

Second line  Pericardial effusion  Quantification: ◦ Trivial: Effusion only seen in systole ◦ Small: <1 cm ◦ Moderate: 1–2 cm of pericardial fluid ◦ Large: >2 cm ◦ Very large: >2.5 cm  Qualitative assessment ◦ Transudative effusions: dark on the T1-weighted sequences ◦ Proteinaceous effusions: bright on T1-weighted sequences and dark on T2-weighted sequences ◦ Exudative effusion: medium intensity on T1 and medium to bright on T2-weighted sequences ◦ Hemorrhagic effusions: bright on both sequences but can evolve to a chronic hematoma with low signal intensity and dark foci signifying hemosiderin deposition surrounded by a dark peripheral rim

Tamponade

First line  Cavitary collapse of the right atrium in early systole  Cavitary collapse of the right ventricle in early diastole  Hepatic veins diastolic flow reversal on expiration  Plethoric IVC (defined as an IVC diameter >2.1 cm and associated with <50% reduction in its diameter with inspiration)  Inflow variation ◦ Mitral >30% ◦ Tricuspid >60%

Not recommended

Not recommended

Constriction

First line  Ventricular interdependence ◦ Presence of a septal bounce ◦ Respirophasic shifting of the septum ◦ Respiratory variation of the mitral/tricuspid inflows upon Doppler interrogation  Increased medial mitral annular velocities (“annulus reversus”) and the reversed linear relation of the E/e 0 ratio to LA pressure (“annulus paradoxus”)  Plethoric IVC  Hepatic vein flow diastolic reversal with expiration  Myocardial strain analysis showing reduced circumferential strain, reduced early diastolic twisting and LV torsion; global longitudinal strain is often preserved  Decreased regional LV anterolateral wall and RV free wall strain with preserved septal strain (“strain reversus”) suggesting peri-myocardial tethering

Second line  Increased pericardial thickness (4–20 mm)  Calcium burden seen in 50% of cases including the degree and extent  Tubular deformation of the ventricles  Biatrial enlargement  Straightening of the interventricular septum.  Dilatation of the IVC and hepatic veins along with the presence of hepatosplenomegaly, ascites, and pleural effusions suggesting impaired atrial filling  Additional information to a surgeon for pre-op planning for pericardiectomy

Second line  Increased thickness of the pericardium  Pericardial effusion  Tubular shape deformation of the right ventricle due to the constricting pericardium  Abrupt cessation of diastolic filling of the ventricles  Abnormal diastolic septal motion with real-time free-breathing sequences (sensitivity, 81%; specificity, 100%)  Real-time phase-contrast sequences acquired over 10 s during unrestricted breathing to identify respiratory variation exceeding 25% in the transmittal valve flow and respiratory variation exceeding 45% across the tricuspid valve  CMR tagging sequences can quantify deformation over time and can help evaluate pericardialmyocardial tethering  Presence of DHE in the pericardium represents inflammation and an increased T2 STIR signal represents edema

CMR ¼ cardiac magnetic resonance; CT ¼ computed tomographic; DHE ¼ delayed enhancement; HU ¼ Hounsfield units; IVC ¼ inferior vena cava; LA ¼ left atrial; LV ¼ left ventricular; RV ¼ right ventricular; STIR ¼ short-tau inversion recovery; SVC ¼ superior vena cava.

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constrictive

pathophysiology,

or,

rarely,

more

persistent constriction.

autoimmune disorders underlie the etiology, or if there is a contraindication to nonsteroidal anti-

can

inflammatory drugs such as allergies, significant

extend to the epicardial fat and myocardium, referred

kidney injury or disease, or pregnancy, low-dose

MYOPERICARDITIS. Pericardial

inflammation

to as myopericarditis, and similarly, inflammation

steroids can be used as alternative first-line agents

within the myocardium can extend outward, toward

(4). Refractory symptoms may cause a physician to

the pericardial layers, and is defined as peri-

combine these 2 regimens (so-called triple therapy)

myocarditis. This overlap forms the basis of a spec-

and often results in a short period of quadruple

trum with 1 extreme comprising isolated myocarditis,

therapy with the introduction of steroid-sparing

followed by perimyocarditis, myopericarditis, and

medications, including azathioprine. Anakinra, an

ultimately isolated pericardial inflammation (2,22).

interleukin-1 receptor antagonist, and rilonacept, a

The involvement of the myocardium in inflammatory

dimeric fusion protein that inhibits interleukin-1,

pericardial syndromes has been reported to be as high

have classically been limited to very resistant cases

as 23.5% in cases of myopericarditis and 5.4% in cases

with debilitating disease. However, with very reas-

of perimyocarditis, which is not surprising given the

suring findings in randomized trials and increasing

overlap in underlying etiologies (22).

clinical experience, they are being introduced earlier

Myocardial involvement is suspected in the pres-

in the disease course (27). Close clinical follow-up is

ence of elevated cardiac biomarkers (troponins),

required, as the pericardiologists seek to determine

localized

cardiac

not only which medications are best suited but the

arrhythmia, and/or new or worsening global or

appropriate tapering schedule. Guideline-directed

segmental left ventricular (LV) systolic function (23).

therapy suggests tapering when there is clinical

In a cohort of 486 patients with acute myopericardial

and biochemical resolution, often resulting in a

inflammatory syndromes, the presence of myocardial

premature and rapid taper with an increased risk for

inflammation was associated with more future re-

recurrence. Similarly, the treatment of transient and

currences (32% vs. 11%) (22). There was no association

effusive

with persistent worsening of LV systolic function or

inflammatory medications and close observation. In

electrocardiographic

changes,

CP

typically

includes

a

trial

of

anti-

deaths. Nevertheless, the European Society of Cardi-

the more chronic, fibrocalcific phases of CP, with

ology guidelines classify the presence of myocardial

resultant right heart failure, treatment often in-

involvement as a minor criterion for hospital admis-

cludes

sion in the acute setting (4).

diuresis.

TREATMENT OF PERICARDIAL DISEASES

pericardiectomy is warranted to relieve the symp-

symptom

management

with

aggressive

Sometimes, although in rarer circumstances (1%), toms of chronic pericardial inflammation (2). Surgery,

The treatment of acute pericarditis involves anti-

in this instance, can be more technically challenging,

inflammatory medications that can be escalated in a

so a trial of preoperative anti-inflammatory therapy

stepwise fashion with the aims of: 1) decreasing

can be helpful. In recent times, in addition to baseline

inflammation of the pericardium; 2) alleviating

diagnostic imaging, there has been increased interest

symptoms and improving quality of life; 3) mini-

in imaging-guided treatment strategies for pericar-

mizing the risk for recurrence; and 4) ultimately

ditis as a means by which to optimize therapeutic

preventing evolution into a chronic debilitating

interventions (8).

constrictive state. The anti-inflammatory medications include nonsteroidal anti-inflammatory drugs

CARDIAC IMAGING FOR

and acetylsalicylic acid (ASA). The addition of

PERICARDIAL DISEASES

colchicine has been shown in randomized controlled trials to produce more rapid symptom resolution and

CURRENT AND EVOLVING INDICATIONS. There are 3

a significant reduction in recurrences (24,25). Exer-

imaging modalities commonly used to interrogate the

cise restriction is commonly suggested and is sup-

pericardium, characterize it, and ascertain any he-

ported mostly by anecdotal evidence (26). Low-dose

modynamic influences imposed on the heart as a

steroids (0.5 mg/Kg) are typically reserved for pa-

consequence

tients who have failed first-line “dual therapy” with

(Table 1). These include echocardiography, CCT, and

colchicine and high doses of a nonsteroidal anti-

CMR (28). The consensus statements on the use of

inflammatory drug because of an associated risk for

multimodality imaging for the diagnosis and man-

recurrence. However, if conditions such as systemic

agement of pericardial disease (10,29) as well as

of

ongoing

pericardial

pathology

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the most recent iteration of guidelines for the management and diagnosis of pericardial diseases (29) suggest echocardiography as the first-line imaging

F I G U R E 4 Suggested Algorithm for the Management of Symptomatic

Pericardial Effusions

modality for all pericardial diseases, while CCT and

Pericardial Effusion

CMR are reserved for inadequate echocardiographic windows and/or diagnostic uncertainty. Since their publication in 2013 and 2015 respectively, it has

Assess Echo and Clinical Hemodynamics

become clearer that the indication for advanced im-

Hemodynamically significant

aging and characterization of the pericardium is broader and should include most cases of complicated pericarditis and most cases of CP with the objective of better characterizing the pericardium and

Clinical Hypotension Tachycardia Pulsus Paradoxus

Echo RA/RV inversion IVC plethora Respiratory Inflow Variation

improving classification of the disease states (2) (Figure 2).

Yes

ECHOCARDIOGRAPHY. Echocardiography

is

No

the

Presence of Pericardial Inflammation - CMR (DHE+/T2STIR+) - ↑CRP/ESR

safest and most accessible imaging modality and is currently the initial recommended imaging test for all pericardial diseases. In acute and recurrent pericarditis, echocardiography can sometimes identify a

No

Yes

thickened pericardium, is diagnostic of a pericardial

Anti-Inflammatories

effusion, and offers enough temporal resolution and hemodynamic assessment to diagnose tamponade

Serial follow-up

physiology and/or suggest the presence of constrictive physiology (10). That being said, the most common finding in acute pericarditis is a normal result

Refractory

(11). Echocardiography is nevertheless a diagnostic

Yes

criterion for acute and recurrent pericarditis, and it should be ordered within the first 24 h of a suspected

No

Pericardial Drainage Indicated

diagnosis (4). The presence of regional abnormalities may suggest involvement of the myocardium (2),

Clinical

while the presence of an echo-free space between the

- Hemopericardium - Need for biopsy - Multiple previous effusions

layers of the pericardium diagnoses an associated pericardial effusion (30,31) (Table 1, Figure 4). Tam-

Echo - Small effusion - Loculated effusion - Posterior location

ponade physiology is then suggested when the effusion is accompanied by right atrial and/or right

Yes

No

Surgical Pericardial Window

Percutaneous Pericardiocentesis

ventricular cavity inversion, a plethoric inferior vena cava, and evidence of interventricular dependence by inflow variations (mitral inflow variation of 30%, tricuspid inflow variation of 60%). The presence of constrictive physiology is more challenging and requires a constellation of findings on echocardiogra-

A proposed flow diagram demonstrates the critical elements in the decision to undergo

phy. Welch et al. (32), in a series of 130 patients with

either surgical or percutaneous pericardiocentesis, emphasizing the complementary role

surgically confirmed CP, determined that an E/A ratio

of echocardiography and clinical assessment. CMR ¼ cardiac magnetic resonance;

>0.8 with a plethoric inferior vena cava, a respirophasic shift of the interventricular septum (Video 1), “annulus reversus” with a minimum septal mitral

CRP ¼ C-reactive protein; DHE ¼ delayed hyperenhancement; ESR ¼ erythrocyte sedimentation rate; IVC ¼ inferior vena cava; RA ¼ right atrial; RV ¼ right ventricular; STIR ¼ short-tau inversion recovery.

annular e0 velocity of 8 cm/s, and exaggerated hepatic expiratory end-diastolic flow reversal are diagnostic. Furthermore, pericardial tethering can be suggested

referred to as “strain reversus.” Other findings can

using

supra-

support the diagnosis as well (Table 1, Figure 3).

physiologic longitudinal deformation of the septal

Echocardiography is the ideal tool for serial imaging

segments with an associated abnormal lateral longi-

and follow-up and is particularly useful to monitor

tudinal deformation is a phenomenon currently

disease activity if there is a baseline abnormality or to

strain

imaging.

The

presence

of

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F I G U R E 5 Cardiac Magnetic Resonance Imaging–Guided Staging of Pericardial Inflammation

Black Blood

Echocardiogram

T2 STIR

DHE

A supine

Acute

*

SubAcute

Healed

B Burned Out

(A) A 27-year-old woman presenting with 6 recurrences of acute pericarditis. Initial echocardiography shows a thickened pericardium (asterisk) and a small effusion (arrow). Cardiac cardiac magnetic resonance shows acute inflammation with a thickened pericardium on black-blood images (arrow), pericardial enhancement on T2 short-tau inversion recovery (STIR) and delayed hyperenhancement (DHE) images (arrow). Triple therapy was intensified and anakinra introduced. Subsequent imaging showing a normal pericardium on echocardiography and black-blood sequences with interval resolution of the T2 STIR enhancement and persistence of signal on DHE suggesting a subacute stage of inflammation. After 8 months of treatment, there was resolution of the DHE on fat supressed imaging, with a normal-looking pericardium on echocardiography and black-blood sequences and normal T2 STIR, suggesting a healed pericardium. (B) A 44-year-old man with a history of idiopathic pericarditis now presents with right heart failure despite medical therapy. Echocardiography appears normal, but black-blood sequences show a thickened pericardium (arrow). Furthermore, there is no signal on T2 STIR and DHE, suggesting a burned-out pericardium. Given his refractory symptoms he was referred for pericardiectomy.

monitor for evolving constrictive physiology. Echo-

acquisitions, CCT is the most accurate imaging mo-

cardiography, however, is limited in its ability to

dality for the measurement of pericardial thickness

quantify pericardial inflammation or suggest peri-

and the most sensitive imaging modality to detect

cardial healing.

pericardial calcifications (33) (Figure 3). In the setting of acute and recurrent pericarditis, a noncalcified

CCT. CCT requires iodinated contrast injections and

thickened smooth pericardium (8) (>2.0 mm) with an

ionizing radiation and is less reliable in patients with

associated pericardial effusion and iodinated contrast

rapid and/or irregular heart rhythms. It is currently a

enhancement of the visceral and parietal surfaces are

second-line imaging modality for the diagnosis and

suggestive of ongoing inflammation (34). Should the

management of pericardial conditions. With its su-

contours have a more irregular shape, a certain de-

perior spatial resolution, it offers primarily anatomic

gree of chronicity can be invoked. Although there are

information. Using a multidetector computed tomo-

limited and indirect findings on CCT consistent

graphic

with cardiac tamponade, CCT is not a primary

scanner

and

high-resolution

volumetric

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recommended imaging modality for the diagnosis of

However, these water-sensitive sequences are sus-

cardiac tamponade (Table 1). CCT may be more

ceptible to motion and are also sensitive for the

informative when investigating CP (34). CCT can

detection of pericardial effusions, which themselves

accurately measure pericardial thickening (seen in up

may vary in signal intensity on the basis of their

to 50% of cases of CP) (14). The pericardium has been

composition, rendering the detection of concomitant

described, in more acute stages, to range from 4 mm

pericardial edema a challenge to differentiate (2,37).

to up to 20 mm. CCT can also measure and describe

Lastly, late or delayed gadolinium enhancement

the presence, degree, and location of pericardial cal-

(delayed hyperenhancement [DHE]) sequences (10 to

cifications (also seen in up to 50% of cases). Overall,

20 min after the injection of gadolinium) can be used

although CCT can inform about the anatomy and

to detect and grade the severity of ongoing pericar-

suggest an inflamed pericardium, it offers minimal

dial inflammation (8). Given the relatively avascular

hemodynamic information and is not ideal for serial

nature of the pericardium, a healthy pericardium will

imaging. Consequently, CCT is not used often to di-

not retain gadolinium resulting in a null signal when

agnose or guide therapy when managing inflamma-

capturing delayed images. An injured pericardium,

tory pericardial conditions, aside from characterizing

however, will lead to neovascularization, fibroblast

calcium burden and planning for pericardiectomy.

proliferation, and an expanded extracellular space, attracting gadolinium and delaying its washout,

CMR. CMR has emerged as the most comprehensive

resulting in increased signal on delayed sequences

modality to assess the pericardium, because it allows

(Figure 5). Furthermore, the addition of a fat sup-

morphological assessment, characterization of the

pression sequence allows better differentiation of

pericardium, and assessment of the associated he-

inflamed pericardium from adjacent visceral or

modynamic parameters through the integration of a

epicardial adipose tissue. In a study of 25 patients

number of sequences within the same study (35).

with biopsy-proven CP who underwent CMR, Zurick

Furthermore, it offers higher spatial resolution than

et al. (9) were able to demonstrate a correlation be-

echocardiography and does not depend on ionizing

tween DHE and histological markers of chronic

radiation. It is, however, limited by accessibility and

inflammation. More specifically, the presence of DHE

the presence of irregular heart rhythm. CMR allows a

was associated with a trend toward greater granula-

clinician to confidently diagnose acute pericarditis by

tion tissues, hyperemia, and increased vasculariza-

directly demonstrating signs of pericardial inflam-

tion, which may explain the increased uptake of

mation. CMR is also a reliable modality for the diag-

gadolinium. There seems to be, on the basis of the

nosis of constriction (Table 1) (36). A typical protocol

limited number of studies available, a correlation

for suspected pericarditis and/or CP often includes

between pericardial vascularity, active inflammation,

transverse black-blood spin-echo images for the

and delayed enhancement, a relationship that may

detection of abnormal pericardial thickening (<4 mm

have some degree of linearity (9,14). Pericardial

is considered normal) and steady-state free preces-

thickness, however, did not demonstrate such a clear

sion cine sequences to assess overall ventricular

association (9) and is believed to be suggestive of

function and the presence of a pericardial effusion. A

end-stage pericardial fibrosis. Feng et al. (14), in a

pericardial effusion can then be quantified and char-

group of 29 patients with CP, were able to demon-

acterized with the integration of subsequent se-

strate that patients with thickened pericardium

quences (Table 1). These steady-state free precession

(>3 mm) and little or no imaging or biochemical ev-

cine images can also identify features consistent with

idence of inflammation would not improve with anti-

constrictive physiology, including the presence of a

inflammatory

diastolic septal bounce or shudder, conical or tubular

thickened pericardium and signs of inflammation did

deformities of the ventricles, LV or right ventricular

have improvement in pericardial thickness and

tethering, and inferior vena cava enlargement. A free

pericardial compliance. Most important, CMR ,

breathing

the

including DHE and T2 STIR sequences, may help

assessment of respirophasic septal shift representing

guide the intensity of anti-inflammatory therapy and

ventricular

immunotherapy

sequence

can

be

interdependence,

performed the

for

hallmark

of

medications,

when

whereas

patients

those

with

demonstrate

re-

constrictive physiology (Video 2). T2-weighted se-

fractory symptoms (38). Serial imaging for patients

quences such as T2 short-tau inversion recovery

with recurrent or refractory symptoms can be helpful

(STIR) are sensitive for the detection of relative in-

for clinicians to stage the disease and objectify

creases in water content and can suggest the pres-

pericardial

ence of edema to implicate active inflammation.

medications.

healing

before

beginning

to

titrate

11

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Although CMR does offer many advantages, there

beyond the presence of inflammation (38). CMR

are certain limitations worth accounting for. Simple

characterization

transudative pericardial effusions are expected to

increasingly relied upon in clinical practice. In the

have high signal on T2-weighted black-blood se-

presence of DHE in the setting of an isolated episode

of

the

pericardium

has

been

quences. However, cardiac-related nonlaminar mo-

of pericarditis, the diagnosis of pericardial inflam-

tion may change the signal intensity (typically seen in

mation can be easily made and can clarify any diag-

smaller pericardial effusions). Also, ability to discern

nostic confusion with a very specific and definitive

pericardial inflammation from adjacent fat can be

diagnosis. Once the diagnosis is made, staging the

fat-

degree of underlying inflammation can then help

suppressed delayed sequences, the fat suppression

difficult

on

delayed

sequences.

Even

on

guide therapy. T2 STIR images, by way of identifying

may not be uniform and may pose interpretation

the presence of edema, classify the disease into an

challenges, more often seen with subtle or mild cases.

active and a more acute stage, while the absence of a

POSITRON EMISSION TOMOGRAPHY. Positron emis-

signal on T2 STIR images suggests a more subacute or

F-fluorodeoxyglucose

chronic stage of disease. These CMR imaging se-

is most frequently used to assess for inflammation

quences have paved the way for imaging-based

sion tomography (PET) with

18

F-flu-

staging of pericarditis: acute, subacute, and healed

orodeoxyglucose PET to detect pericardial inflam-

or burned out (Central Illustration, Figure 5). The

mation, however, is less common. First described in a

presence of inflammation in the acute stages (DHE

patient with post-pericardiotomy syndrome (39), PET

positive or T2 STIR positive) would prompt either

has since been found to predict steroid responsive-

initiation or escalation of therapy. Conversely, reso-

ness in cases of CP (40). In a series of 16 patients with

lution of pericardial edema (subacute stages) with

the diagnosis of CP, 50% of which were tuberculous in

alleviation of symptoms could suggest slow pericar-

nature

of

dial healing, reassuring the clinician that the tapering

maximum standardized uptake value were higher at

process can begin. In cases of both recurrent and

baseline (5.8  4.0) for responders to therapy

chronic disease, the presence of DHE (with or without

compared with nonresponders after a 3-month period

edema) while on therapy may constitute a failure of

of steroid therapy. In a subsequent study, increased

therapy or a more aggressive case and prompt either

pericardial signal was associated with an increased

escalation with introduction of biologics or a more

risk for recurrence (41). Furthermore, fusion PET-

protracted tapering. Finally, absence of both signals

and increased metabolic activity. The use of

and

31%

idiopathic,

18

measurements

CMR has been reported to provide added diagnostic

would indicate either a healed or “burned-out” peri-

utility in active pericarditis (42). Fluorodeoxyglucose

cardium. In a recent observational study of 200 pa-

PET may prove to be useful, particularly in patients

tients with recurrent pericarditis, not only did the

with pacemakers or contra-indications to CMR, but

addition of CMR and DHE sequences add to the con-

future studies are needed.

ventional clinical criteria for diagnosis (net reclassi-

THE EMERGING ROLE OF MULTIMODALITY

treatment tailored to CMR findings resulted in a

IMAGING TO STAGE PERICARDIAL DISEASE

quicker remission and less steroid therapy. This was

fication improvement ¼ 0.80; p < 0.001), but

largely because of a more effective and tailored The decision to treat, taper, or stop therapy when

tapering regimen than clinical and biomarker cues,

managing

which can be very misleading in the setting of strong

inflammatory

pericardial

diseases

is

dependent on the stage of disease, more specifically, the extent of ongoing inflammation. Pericardial

anti-inflammatory medications (13). In the presence of constrictive physiology, DHE

inflammation can be monitored with laboratory bio-

and a

markers such as high-sensitivity C-reactive protein

concomitant acute pericardial inflammation and

signal on T2 STIR

sequences

indicates

(CRP) and sedimentation rates. Feng et al. (14)

evokes a likely diagnosis of transient constriction. A

described a correlation between systemic inflamma-

more subacute pattern (T2 STIR negative and DHE

tory markers and pericardial DHE, but in a subse-

positive) with a pericardial effusion (with or without

quent

159

tamponade) suggests a transitional or subacute stage

patients with recurrent pericarditis, the correlation

similar to effusive CP (43). Once the diagnosis is

was found to be modest at best (38). Furthermore,

made, serial imaging can further objectify the tran-

anti-inflammatory medications can rapidly normalize

sition to different stages of disease. Complete

these markers well before resolution of the pericar-

absence of pericardial hyperenhancement and/or

dial inflammation, making these biomarkers even

marked calcifications on chest radiography or CCT

less reliable for characterizing the stage of disease

with ongoing constrictive findings on cardiac imaging

retrospective

observational

study

of

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F I G U R E 6 Multimodality Imaging in Perimyocarditis

A

C

*

B

D

*

(A) Electrocardiogram showing ST-segment elevation and PR-segment depression confined to the inferior limb leads. (B) Longitudinal 2-dimensional speckle-tracking bull’s-eye plot, demonstrating abnormal strain values in the midinferior and midinferoseptal segments. (C) Short-axis T2 short-tau inversion recovery cardiac magnetic resonance (CMR) showing increased myocardial (asterisk) and pericardial (arrow) signals within the midinferior and inferoseptal segments. (D) Short-axis CMR delayed sequences after injection of gadolinium contrast agent showing increased myocardial (asterisk) and pericardial (arrow) signals within the midinferior and inferoseptal segments. This constellation of findings is consistent with perimyocarditis.

suggest that the disease is chronic and irreversible

p ¼ 0.06) demonstrating a trend toward clinical

and often requires diuresis and possible

peri-

improvement (45). They, do however, have similar

cardiectomy (Figure 3). Although any active inflam-

limitations as those previously described for acute

mation indicates the potential for reversibility and

pericarditis and can often been nonrepresentative of

mandates

the degree of ongoing pericardial inflammation.

a

trial

of

anti-inflammatory

therapy,

objectifying minimal or no residual inflammation is

CMR has also emerged an important tool for the

important in ensuring a safe and successful peri-

noninvasive diagnosis of myocarditis. Similar to

cardiectomy (44). Inflammatory biomarkers can and

the evaluation of the pericardium, characterization of

have been used as markers of pericardial inflamma-

the myocardium in the appropriate clinical context

tion in the setting of constriction. These markers have

can provide insight on myocardial involvement. The

shown an association with clinical improvement, with

diagnosis rests on 3 major components, which

Westergren sedimentation rate leading the way (30

constitute the Lake Louise criteria (46): 1) identifying

vs. 6 mm/h; p ¼ 0.004) and CRP (22.8 vs. 10.2 mg/l;

the presence of myocardial edema by T2-weighted

13

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Therapies for Pericardial Conditions

imaging; 2) myocardial hyperemia on the basis of

prognosis for admission (4). In a more recent

comparative imaging before and after early contrast

observational

injection; and 3) assessment for myocardial fibrosis

important independent prognostic value (38). In a

on delayed sequences. In a more recent iteration,

cohort of 159 patients who had recurrent pericar-

Ferreira et al. (47) emphasized the use of noncontrast

ditis (median number of recurrences 3), Kumar

parametric imaging to identify these 3 components of

et al. (38) stratified pericardial enhancement on

myocardial inflammation (Figure 6).

delayed gadolinium images into 4 quartiles of

CMR

was

found

to

have

quantified enhancement: #26 cm 3, 26 to 48 cm 3, 48

ESTABLISHING PROGNOSIS AND THE

to 71 cm 3, and quantified enhancement of >71 cm 3.

POTENTIAL ROLE OF MULTIMODALITY IMAGING ACUTE

study,

Lower quantitatively defined DHE was found to be an independent risk factor for remission (HR: 0.77;

OR RECURRENT PERICARDITIS. After an

initial encounter and subsequent diagnosis of acute pericarditis, it is important to establish the risk for an immediate adverse event and the likelihood of a recurrence (2). Imazio et al. (48) retrospectively surveyed a cohort of 453 patients in 1 of the earlier observational studies attempting to answer this question from a clinical standpoint. They described a number of clinical risk factors for the development of complicated pericarditis, defined as persistence of symptoms, recurrence, tamponade, and development 

of CP. Fever >38 C (hazard ratios [HR]: 3.56; 95% confidence interval [CI]: 1.82 to 6.95; p < 0.001), subacute course (HR: 3.97; 95% CI: 1.66 to 9.50; p ¼ 0.002), large effusion and tamponade (HR: 2.15; 95% CI: 1.09 to 4.23; p ¼ 0.026), and resistance to anti-inflammatory medications (HR: 2.5; 95% CI: 1.28 to 4.91; p ¼ 0.008) were all identified as risk factors for complicated pericarditis. Identification of an underlying etiology was also identified as a risk factor and is now reflected in the guidelines as an indication for admission (4). In a subsequent retrospective analysis, Imazio et al. (49) surveyed 100 patients with recurrent pericarditis and found that

high-dose

steroids (1 mg/kg) were associated with more recurrences and hospitalizations compared with lowdose (0.2 to 0.5 mg/kg) steroids (HR: 3.61; 95% CI: 1.96 to 6.63; p < 0.001). The number of recurrences

95% CI: 0.64 to 0.93; p ¼ 0.008), while the highest quartile (>71 cm 3) was associated with less clinical remission overall (p ¼ 0.047) and a higher recurrence rate at 6 months (odds ratio: 1.14; 95% CI: 1.02 to 1.29; p ¼ 0.026). Furthermore, higher DHE quantification values were associated with a shorter interval

to

subsequent

recurrences

(HR:

1.01;

95% CI: 1.00 to 1.01; p ¼ 0.012), and the time to remission was significantly prolonged, with 72% of patients within the highest quartile achieving clinical, biochemical, and CMR remission at a mean of 4 years after initiation of treatment (38). Although the addition of high-sensitivity CRP (per 1 mg/l increase) to baseline characteristics offered an integrated

discrimination

compared

with

improvement

baseline

of

0.4%

characteristics

alone

(95% CI: 0.1% to 4.0%; p ¼ 0.244), quantitative DHE (per 10-cm 2 increase) offered an integrated discrimination improvement of 8% (95% CI: 2% to 18%; p < 0.001), highlighting that quantitative DHE, and less so qualitative DHE, offers important incremental value to both clinical and inflammatory biomarkers to predict clinical remission. Of note, DHE had only a modest correlation with inflammatory markers (high-sensitivity CRP), likely in the context

of

active

anti-inflammatory

therapy,

rendering laboratory biomarkers less reliable than imaging biomarkers like CMR.

also plays a very important prognostic role, with a

CP. In the setting of CP, clinical features that affect

well-described 15% chance of recurrence after the

prognosis include ongoing evidence of inflammation

first episode, a risk that increases to 50% thereafter.

through symptoms such as active chest pain and

Lastly,

hold

elevated inflammatory biomarkers. Feng et al. (14), in

some limited prognostic value. An elevated high-

a group of 29 patients with CP, were able to demon-

sensitivity CRP level at 1 week was associated

strate that higher baseline CRP and Westergren sedi-

with significantly lower recurrence-free survival,

mentation rate were associated with reversible

elevated

inflammatory

biomarkers

likely reflecting the extent of ongoing inflammation

disease. Although the clinical stratification is often

(50).

limited, imaging offers important incremental infor-

Cardiac imaging has recently demonstrated to have

mation as well. The presence of DHE, signifying

additive prognostic value. On initial echocardiogra-

active inflammation, can either classify a patient as

phy or CMR, regional or global LV dysfunction or

having transient CP with an overall excellent prog-

abnormal segmental strain suggests associated myo-

nosis or suggest the possibility of reversible disease.

pericarditis (2) (Figure 6); a minor predictor of poor

In a cohort study of 41 consecutive patients with CP

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anti-inflammatory medications are the mainstay of

HIGHLIGHTS

therapy, individualized therapy and tapering are

 Cardiac imaging is important in diagnosing acute and chronic pericardial inflammation.

often needed to avoid these poor outcomes. Cardiac

 Cardiac imaging has redefined the approach of pericardiologists to diagnosis.

tion of acute and more chronic pericardial inflam-

 Image-guided therapies can improve overall outcomes and shorten durations of therapy.

namic status suggestive of constrictive physiology.

imaging, particularly CMR, has recently emerged as an important tool for the diagnosis and prognosticamation. CMR can describe pericardial anatomy, identify and grade the severity of active inflammation on DHE sequences, and ascertain cardiac hemodyFurthermore, the presence of T2 signal helps define the stage of inflammation, recognizing that there are more acute, subacute, and chronic states of disease

who underwent CMR, quantitative DHE performed

and depending on the stiffness of the pericardium

best when establishing the association with clinical

may be associated with constrictive physiology, ulti-

improvement (area under the receiver-operating

mately reinforcing the concept that these inflamma-

characteristic curve 0.83; p < 0.0001), while West-

tory syndromes are not mutually exclusive but rather

ergren sedimentation rate had an area under the

phenotypes in a wider spectrum of inflammatory

receiver-operating

characteristic

curve

of

0.76;

disease. Furthermore, quantification of the pericar-

p ¼ 0.001) (46). Furthermore, quantitative analysis

dial enhancement on delayed imaging provides

revealed a strong association with clinical improve-

prognostic information and serves as an effective tool

ment, with higher values offering better outcomes

for individualized therapeutic plans and follow-up.

(77 cm 3 vs. 31 cm 3 of DHE; p < 0.001). The presence of

Other clinical biomarkers and imaging modalities

inflammation, clinically, biochemically, or using im-

can offer some information, but none more compre-

aging biomarkers, is a clear indication for medical

hensive than CMR, which should be used early in

therapy and highlights the potential for reversibility

cases of complicated and/or constrictive pericarditis.

(Central Illustration).

CONCLUSIONS

ADDRESS FOR CORRESPONDENCE: Dr. Allan L Klein,

Center for the Diagnosis and Treatment of Pericardial Acute inflammation of the pericardium is often a

Diseases, Department of Cardiovascular Medicine,

benign condition. In up to one-third of cases, how-

Cleveland Clinic, 9500 Euclid Avenue, Desk J1-5,

ever, it can recur, becoming complicated, and it can

Cleveland,

be associated with signs of constriction. Although

Twitter: @AllanLKleinMD1.

Ohio

44195.

E-mail:

[email protected].

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KEY WORDS constrictive, delayed enhancement, pericarditis, treatment

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