Review Article :
Peri-Myocardial Infarction Pericarditis: Current Concepts
Gharacholou S Michael, Vaca-Cartagena F Bryan,
Parikh P Pragnesh, Pollak M Peter and Bruce J Charles
Abstract
Peri-Myocardial Infarction Pericarditis (PMIP), or epistenocardiac pericarditis, has been considered a relatively benign condition occurring within a few days after Myocardial Infarction (MI). Although the condition usually does not require specific treatment, the finding of a pericardial friction rub in the post-MI patient does prompt a careful review of post-MI symptoms and test results, including dysrhythmia recordings, Electro-Cardio Grams (EKG), and the Transthoracic Echocardiogram (TTE) to exclude potentially life threatening post-MI mechanical complications such as free wall rupture. The auscultatory findings of a pericardial rub often represent a teaching opportunity for house staff and students, yet given the self-limited course of PMIP, very little is known regarding the mechanism, biology, imaging findings, and management strategy in patients with and without symptoms. We review the current understanding of PMIP for clinicians caring for post-MI patients.
Full-Text
Pericardial
Anatomy
The pericardium is
functionally a dual layer sac of outer fibrous and inner serosal (visceral)
layer that contains the heart and normally less than 50 mL of pericardial fluid
[1]. The outer fibrous layer is in continuity with the great vessels above and
with the diaphragm below and is in direct contact with many mediastinal
structures such as the pleura, bronchi, esophagus, and rib costal cartilage.
Measuring less than 1mm in thickness, the pericardium is composed of collagen,
elastic fibers, fibroblasts, and mesothelial cell layers
along the parietal and serosal pericardium [1]. Regardless of etiology, injury
to the pericardium generally results in a non-specific response with generation
of fluid and inflammatory cells with formation of fibrinous adhesions during
convalescence.
Cardiac-Pericardial
Injury Syndromes
The cardiac and pericarditic injury syndromes, often referred
to as Post-Cardiac
Injury Syndromes (PCIS), are categorized into PMIP, Post-Pericardiotomy Syndrome (PPS), and
post-traumatic pericarditis. It is postulated that PMIP and PPS have a similar
biologic basis, evoking an antibody response to cardiac cellular components and
contractile proteins. However, this response is perhaps magnified in PPS owing
to greater tissue injury following cardiac surgery. Immune complexes trigger
inflammatory responses in the pericardium [2,3].
Post- traumatic etiologies include iatrogenic and
non-iatrogenic factors. The most common iatrogenic culprits are percutaneous
cardiac procedures such as pacemaker lead insertion, cardiac ablation
procedures, percutaneous coronary interventions, endomyocardial biopsies, and
structural heart procedures. Non-iatrogenic factors include trauma to the chest
wall or aortic dissection. Post-infarction etiologies are grouped by timing,
with early (<7 days post MI) involvement consistent with PMIP while a
delayed (>7 days to months) involvement consistent with Dressler syndrome (late or
delayed pericarditis). First described in 1956 by William Dressler, the delayed
post infarction syndrome may present with symptoms similar to those with acute
idiopathic pericarditis including pleuritic chest discomfort or pain across the
trapezius ridge, fever, and signs of a pericardial friction rub [4].
The European Society of Cardiology has proposed diagnostic
criteria for PCIS when at least 2 of the 5 following criteria are met: 1) fever
without alternative explanation, 2) pericarditic or pleuritic chest pain, 3)
pericardial or pleural friction rub, 4) pericardial effusion and/or 5)
pleural effusion with elevated C-reactive protein [5]. Regardless of etiology,
the typical EKG findings of PCIS include widespread ST-segment elevation often
sparing aVR and V1 along with PR segment depression. However, these EKG changes
are dynamic, evolving over time and ultimately normalize.
There may be associated findings on chest X-ray demonstrating
a pleural effusion or a pericardial effusion on TTE. Pericardial effusions are
usually small without increased intrapericardial pressures and tamponade
physiology. However, ongoing inflammation necessitates serial clinical and TTE
examinations to determine whether the pericardial effusion is enlarging and
requires pericardiocentesis. Treatment of symptomatic patients usually involves
anti-inflammatory medications (aspirin 650 mg every 6 to 8 hours or ibuprofen
600mg every 8 hours) for 7 to 10 days. There is general consensus that aspirin
is the preferred anti-inflammatory in patients post MI, rather than ibuprofen
and other Non-Steroidal
Anti-Inflammatory Drugs (NSAIDs). Patients with contraindications to aspirin
or NSAIDs (severe renal insufficiency, allergies, GI bleeding, or oral
anticoagulants) may be treated with low-dose glucocorticoids (<0.5
mg/kg/day) for 2 to 4 weeks with slow and gradual tapering. In the Investigation on Colchicine
for Acute Pericarditis (ICAP) study, which included 20% (n=48 patients) of
patients with post-cardiotomy pericarditis, the addition of colchicine to
anti-inflammatory therapy significantly reduced the primary outcome of
incessant/recurrent pericarditis (16.7% vs 37.5%; RRR 0.55, 95% CI 0.30-0.72)
[6]. There were no serious adverse events related to colchicine, which had a
similar side effect profile to placebo.
Peri-Myocardial Infarction Pericarditis
PMIP, or epistenocardiac pericarditis, shares some
characteristics to Dressler syndrome but also has notable differences. It has
been suggested that the incidence of PMIP has declined in the era of
reperfusion therapy and may only affect approximately 1% of those with
ST-elevation myocardial infarction [7]. Since PMIP is more likely to occur
after transmural MI, the EKG findings of pericarditis may be masked by the EKG
changes of an evolving MI. Thus, a pericardial friction rub may be the only
diagnostic clue to its presence. Indeed, since the typical pyramidal infarction
zone of the myocardium has its base at the endocardium and apex at the
epicardium, adjacent to the visceral pericardium, it is less
likely to produce diffuse ST elevations as seen in Dressler syndromes [8].
Pericardial friction rubs are characteristically dynamic,
subtle, change with underlying pericardial insult, and rarely persist beyond a
few days. A study of auscultatory and phonocardiographic recordings by an
experienced examiner identified that the majority of pericardial friction rubs
are composed of 3 components: atrial systole, ventricular systole, and protodiastole
(immediately after S2), rather than biphasic to-and-fro as had been originally
characterized [9]. Rubs have a qualitative characteristic of grating or
scratching, and may on rare occasions be palpable [9]. Due to the fleeting
nature of rubs and limitations of auscultation to detect pericarditis, PMIP has
been increasingly incidentally identified using Cardiac Magnetic Resonance (CMR) early
after acute MI. Evidence for pericardial inflammation can be appreciated on
late gadolinium enhancement early after acute MI, often adjacent to the region
of infarct (Figure 1).
Figure 1: 78-year-old
male with evidence of PMIP on cardiac magnetic resonance imaging with late
gadolinum enhancement 1 day after acute inferolateral ST-segment elevation
myocardial infarction. Note the pericardial enhancement (arrowhead) adjacent to
and extending just beyond the inferoateral wall segment with full thickness
zone of infarction (arrow).
In a study of 189 patients undergoing CMR 2 to 5 days after
primary PCI for acute ST-segment elevation MI, 31% of patients had pericardial
inflammation with the majority (60%) of inflammation located in the infarct
zone confirmed on late gadolinium enhancement [10]. Interestingly, diffuse
involvement was present in 28% of those with pericardial inflammation. Those with
pericardial inflammation had larger infarct size, more microvascular
obstruction, and higher levels of CRP, as compared to those without
inflammation. At 4 month follow up CMR, pericardial abnormalities had resolved
in 80% of patients. Indeed, advanced cardiac imaging suggests that PMIP is likely
more common than initially appreciated, with identification of subclinical
PMIP. Since most of these abnormalities show resolution in follow up, further
research is needed to determine the prognostic significance of pericardial
inflammation in post-acute MI. Figure 3
illustrates various degrees of pericardial involvement with late pericaridits
and PMIP as compared to normal pericardium.
Figure 3:
Illustration of normal pericardium as compared to pericardial involvement in
peri-myocardial infarction pericarditis (PMIP) and Dressler syndrome. Note the
regional involvement of the pericardium adjacent to the infarction zone as
compared to a more diffuse and generalized inflammatory involvement in Dressler
syndrome.
Although Imazio et al observed that the incidence of atrial
fibrillation/atrial flutter (AF/AFL) in patients with acute pericarditis ranges
from 4 -7%, pericardial inflammation may not be independently associated with
incident AF/AFL since affected patients were typically older [11].
Nevertheless, some patients with pericarditis develop AF without traditional
clinical risk factors for AF (Figure 2A
and 2B). Furthermore, in an analysis of patients with acute coronary syndrome from
several large clinical trials, the incidence of AF was approximately 7% [12].
Unfortunately, the incidence of PMIP or Dresslers was not reported in this
study, raising the question whether post infarction pericarditis may have
contributed in part to the observed rates of AF [12]. Table 1 compares and contrasts early PMIP with late pericarditis
(Dressler syndrome).
Figure 2: A 46 year
old patient developed pericarditis and atrial fibrillation after PCI for non-ST
elevation myocardial infarction. Note diffuse ST-segment elevation throughout
most leads, sparing lead V1, with ST-segment depression in aVR (2A). A conservative approach was undertaken given
no pericarditic symptoms resulting in resolution of EKG abnormalities 5 days
later (2B).
Table 1: Comparison between PMIP and
Dressler Syndrome.
Treatment
The general approach to patients with PMIP, diagnosed
clinically or by advanced cardiac imaging, is usually supportive and no
specific therapy is recommended since symptoms and signs usually resolve
without intervention. For symptomatic patients, acetaminophen 650 mg scheduled
every 6 to 8 hours for up to 10 days is useful. If patients remain symptomatic,
aspirin 650 mg every 6 to 8 hours can be initiated with tapering once symptoms
improve, usually after 7 to 10 days. Of note, there is a potential bleeding
risk with high dose aspirin in the post PCI patient and is not recommended in
patients on ticagrelor since it reduces drug efficacy [13].
Colchicine may be considered as an adjunct to reduce
recurrence risk. This recommendation is based on practice guideline
recommendations for acute idiopathic pericarditis and limited data [5,6]. Non-steroidal medications (NSAIDs)
are generally avoided in post MI patients since observational studies have
documented increased cardiovascular risk and events (MI and stroke) in patients
with known heart disease [14]. Corticosteroids are also generally avoided in
the post MI patient due to propensity for fluid retention, hypertension, and
their adverse effect on atherosclerotic vascular disease.
Future
Directions
Advanced imaging with CMR has identified both localized and
generalized pericardial enhancement in PMIP. This observation suggests that pericardial
involvement post MI is likely more common than previously thought since the
clinical findings of pericarditis alone may be subtle and go unnoticed. Further
research is needed to establish whether the finding of pericardial enhancement
in PMIP has prognostic significance since clinically diagnosed PMIP generally
has a benign and self-limited course.
Acknowledgments
We thank Michael A. King, senior medical illustrator in the
division of biomedical and scientific visualization at Mayo Clinic Rochester,
for illustration of pericardial images.
References
1. Klein AL,
Abbara S, Agler DA, Appleton PC, Hung J, et al. American Society of
Echocardiography Clinical Recommendations for Multimodality Cardiovascular
Imaging of Patients with Pericardial Disease (2013) J Am Soc Echocardiogr 26:
965-1012. https://doi.org/10.1016/j.echo.2013.06.023
2. Maisch B,
Seferovic PM, Ristic AD, Erbel R, Rienmüller R, et al. Guidelines on the
diagnosis and management of pericardial diseases (2004) Eur Heart J 25:
587-610.
3. De
Scheerder I, Vandekerckhove J, Robbrecht J, Algoed L, De Buyzere M, et al.
Post-cardiac injury syndrome and an increased humoral immune response against
the major contractile proteins (actin and myosin) (1985) Am J Cardiol 56:
631-633. https://doi.org/10.1016/0002-9149(85)91024-0
4. Dressler
W. A post-myocardial infarction syndrome: preliminary report of a complication
resembling idiopathic, recurrent, benign pericarditis (1956) J Am Med Assoc
160: 1379-1383. https://doi.org/10.1001/jama.1956.02960510005002
5. Adler Y,
Charron P, Imazio M, Badano L, Barón-Esquivias G, et al. 2015 ESC guidelines
for the diagnosis and management of pericardial diseases (2015) Eur Heart J 36:
2921-2964. https://doi.org/10.1093/eurheartj/ehv318
6. Imazio M,
Brucato A, Cemin R, Ferrua S, Maggiolini S, et al. A randomized trial of
colchicine for acute pericarditis (2013) N Engl J Med 369: 1522-1528. https://doi.org/10.1056/NEJMc1315351
7. Lador A,
Hasdai D, Mager A, Porter A, Goldenberg L, et al. Incidence and prognosis of
pericarditis after ST-elevation myocardial infarction (from the Acute Coronary
Syndrome Israeli Survey 2000 to 2013 Registry Database) (2018) Am J Cardiol
121: 690-694. https://doi.org/10.1016/j.amjcard.2017.12.006
8. Spodick
DH. Electrocardiographic abnormalities in pericardial disease. In: The
pericardium: a comprehensive textbook (1997) New York, pp: 40-64.
9. Spodick
DH. Pericardial friction: characteristics of pericardial rubs in fifty
consecutive, prospectively studied patients (1968) N Engl J Med 278: 1204-1207.
https://doi.org/10.1056/NEJM196805302782205
10. Doulaptsis
C, Goetschalckx K, Giorgio Masci P, Florian A, Janssens S, et al. Assessment of
early post-infarction pericardial injury by CMR (2013) JACC Cardiovasc Imaging
6: 411-413. https://doi.org/10.1016/j.jcmg.2012.09.014
11. Imazio M,
Lazaros G, Picardi E, Vasileiou P, Orlando F, et al. Incidence and prognostic
significance of new onset atrial fibrillation/flutter in acute pericarditis.
Heart 101: 1463-1467. http://dx.doi.org/10.1136/heartjnl-2014-307398
12. Lopes RD,
Pieper KS, Horton JR, Newby LK, Mehta RH, et al. Short- and long-term outcomes
following atrial fibrillation in patients with acute coronary syndromes with or
without ST-segment elevation (2008) Heart 94: 867-873. http://dx.doi.org/10.1136/hrt.2007.134486
13. Mahaffey
KW, Wojdyla DM, Carroll K, Becker CR, Storey FR, et al. Ticagrelor compared
with clopidogrel by geographic region in the Platelet Inhibition and Patient
Outcomes (PLATO) trial (2011) Circulatn 124: 544-554. https://doi.org/10.1161/CIRCULATIONAHA.111.047498
14. Antman EM,
Bennett JS, Daugherty A, Furberg C, Roberts H, et al. Use of nonsteroidal
antiinflammatory drugs: an update for clinicians: a scientific statement from
the American Heart Association (2007) Circulatn 115: 1634-1642. https://doi.org/10.1161/CIRCULATIONAHA.106.181424
*Corresponding
author:
Gharacholou SM, Mayo Clinic Florida, Jacksonville, FL 32224,
USA, Tel: 904-953-7278, E-mail: gharacholou.shahyar@mayo.edu
Citation:
Gharacholou SM, Vaca-Cartagena FB, Parikh PP,
Pollak PM and Bruce CJ. Peri-myocardial infarction pericarditis: Current
concepts (2019) Clinical Cardiol Cardiovascular Med 3: 23-26.
Keywords
Pericardium, Pericarditic injury syndromes,
Dressler syndrome, Corticosteroids.
