Υποτροπιάζουσες Περικαρδίτιδες: Τι νεότερο; Γεώργιος Λάζαρος Επιμελητής Α Α Πανεπιστημιακή Καρδιολογική Κλινική Ιπποκράτειο Γ.Ν.

Transcription

1 Υποτροπιάζουσες Περικαρδίτιδες: Τι νεότερο; Γεώργιος Λάζαρος Επιμελητής Α Α Πανεπιστημιακή Καρδιολογική Κλινική Ιπποκράτειο Γ.Ν. Αθηνών

2 Recurrent pericarditis after an initial episde f pericarditis ranges frm 15 t 30%, and may increase t 50% after a first recurrence in patients nt treated with clchicine particularly if treated with crticsterids.

3 Cmplicatins f acute pericarditis Imazi M, et al. Circulatin 2011;124:

4 Diagnstic criteria fr acute pericarditis Acute pericarditis is diagnsed when at least 2 f the fllwing criteria are present: Typical chest pain Pericardial frictin rub Suggestive ECG changes (typically widespread ST-segment elevatin, PR depressin New r wrsening pericardial effusin Elevatin f CRP is a cnfirmatry finding and evidence f pericardial inflammatin by an imaging technique (CT r CMR) are cnsidered supprting findings

5 Mst cmmn causes f recurrent pericarditis Cause Frequency Idipathic >70% Systemic Inflammatry Diseases *pst pericarditmy syndrme, pst mycardial and Pericardial Injury Syndrmes* infarctin syndrme, 5-10% pst traumatic Neplastic pericardial diseases pericarditis 5% Autinflammatry diseases 5% Imazi M. Expert Rev Cardivasc Ther 2012;10:

6 Pssible pathgenetic mechanisms underlying recurrent pericarditis 1. Infectius etilgy i. Identificatin f viral genme by PCR in 1/3 f recurrent pericarditis cases, either in the effusin r in epicardial bipsy specimens. 2. Autimmune mechanism It is believed t be invlved in 2/3 f recurrent pericarditis cases. It is supprted by the fllwing findings: i. presence f a latent perid f several weeks, ii. presence f autantibdies in the sera f patients (67% anticardiac 48% antinuclear), iii. respnsiveness t anti-inflammatry therapies, iv. assciatin with ther autimmune prcesses, v. familial ccurrence f recurrences in up t 10% f patients, Brucart A, et al. Autimmun Rev 2008;8: Imazi M. Expert Rev Cardivasc Ther 2012;10:

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8 3. Autinflammatry mechanism Autinflammatry diseases include thse genetic disrders characterized by primary dysfunctin f the innate immune system. They appear with recurrent episdes f sersal inflammatin, leukcytsis, and familial ccurrence. Examples are Familial Mediterranean Fever and the tumr-necrsis factr receptr-1-assciated peridic syndrme (TRAPS accunts fr~6% r recurrent pericarditis cases). Brucat A, et al. Arthritis Rheum 2009;60:2543. Pankuweit S, et al. Herz 2000; 25: Sidirpuls P, et al. Ann Rheum Dis 2008;67: Cantarini L, et al. Clin Res Cardil 2012;101:

9 Diagnstic wrk up Lazars G, et al Cardilgy 2011;119:

10 Management f acute pericarditis Physical activity in patients with IRP must be limited until the cmplete remissin f fever and chest pain. A minimal restrictin f 3 mnths has been arbitrarily defined accrding t expert cnsensus. Lazars G et al. HJC 2009 ;50: Eur Heart J. 2004; 25: Eur J Cardivasc Prev Rehabil 2006;13:

11 Clinical pr prgnstic predictrs fr pericarditis with need fr hspitalizatin Baseline features assciated with a specific (secndary cause) Fever>38 C Subacute nset Large pericardial effusin Cardiac tampnade Lack f respnse t aspirin r NSAIDs after at least 1 week f therapy Baseline features assciated with cmplicated in-hspital curse Mypericarditis Immundepressin Trauma Oral anticagulant therapy Little W et al. Circulatin 2006;113: Lange RA et al. NEJM 2004;351: Imazi M et al. Circulatin 2010;121:

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14 Sterids shuld be administered at a dse f mg/kg/die in case f NSAIDS allergy, intlerance r failure, in advanced kidney disease and in pregnancy after the 20 th week f gestatin, in secndary causes requiring sterids therapy (i.e. autimmune diseases) and pssibly in patients receiving chrnic ral anticagulant therapy.

15 Resistant idipathic recurrent pericarditis (r clchicine-resistant sterid-dependent cases) This definitin shuld apply t cases with hard-tcntrl chest pain and multiple recurrences that require high dses f crticsterids (namely prednisne >12.5mg daily) fr lng perids t be cntrlled. They prbably represent 5-10% f recurrent cases. They shuld be addressed t specialized centers. Imazi M, et al. Circulatin 2010;121: Cantarini L, et al. Clin Res Cardil 2012;101: Imazi M, et al. Expert Rev Cardivasc Ther 2012;10:

16 Treatment ptins i. Use f drug cmbinatins Cmbinatins shuld include 3 drugs and specifically aspirin r an NSAID in the recmmended dses, clchicine and crticsterids. Lazars G, Vlachpuls C, Stefanadis C. Hellenic J Cardil 2009 ;50: Imazi M, et al. Circulatin 2010;121:

17 ii. Classic Immunsuppressive drugs They have a delayed nset f actin (2-6 weeks). Less txic and less expensive drugs (such as azathiprine r methtrexate) shuld be preferred. Azathprine at a dse f mg/kgr/daily is the mst used medicatin. Lazars G, Vlachpuls C, Stefanadis C. Hellenic J Cardil 2009 ;50: Imazi M, et al. Circulatin 2010;121:

18 iii. Anakinra Ratinale fr anakinra administratin: Anakinra is an interleukin-1 (IL-1b) receptr antagnist and autinflammatry diseases have shwn a favrable respnse t intereleukin-1 (IL-1) inhibitin. Vasileiu P, Lazars G, et al. Int J Cardil 2014;172:e463-e464.

19 Mechanism f actin f anakinra Safe efficacius sterid sparing agent. Cncerns: cst and recurrences after drug discntinuatin. IL-1=Interleukin-1 IL-1RI=Interleukin-1 receptr type I IL-1 Ra= Interleukin-1 receptr antagnist Lazars G, Imazi M, et al. J Cardivasc Med 2015, In press

20 iv. Intravenus human immunglbulins Mechanism f actin f IvIg Treatment prtcl 400 t 500 mg iv daily fr 5 cnsecutive days with 1 cycle 1 mnth later in cases f incmplete remissin. Imazi M, Lazars G, et al. J Cardivasc Med 2015, In press.

21 last but nt least * If pericarditis is assciated with a knwn disease*, treatment f the underlying disease thrugh a multidisciplinary apprach is f paramunt imprtance. Uremia Tuberculsis Neplasm Autimmune r inflammatry disease Mycardial infarctin Pstcarditmy syndrme Trauma Artic dissectin Endcrine disrders Chest wall irradiatin Adverse drug reactin-txins Imazi M, et al. Eur Heart J 2013 ;34:

22 Pericardiectmy shuld be reserved nly fr frequent, strngly symptmatic recurrences (especially recurrent tampnade) resistant t medicatin. Referral f these patients t centers with specific expertise in this surgery is recmmended. In a retrspective study in 184 pts ( ) pericardiectmy was very effective in reducing the rate f recurrences with a periperative mrtality f 0% and rate f majr cmplicatins 3%. Maisch B, et al. Eur Heart J. 2004; 25: Khandaker M, et al. May Clin Prc 2012;87:

23 Prgnsis in recurrent pericarditis Despite its negative effect n the patients quality f life, the lng-term prgnsis is gd and patients shuld be reassured abut the benign nature f the disease A recent meta-analysis examined 8 clinical series that included a ttal f 230 patients with IRP. During a mean fllw-up perid f 61 mnths, cardiac tampnade was recrded in 3.5% f cases, while there were n cases f cnstrictive pericarditis r left ventricular dysfunctin. Circulatin. 2007; 115: Am J Cardil. 2007; 100:

24 Peridical revaluatin is imprtant in patients with idipathic recurrent pericarditis! 61 patients wh were referred t a tertiary hspital fr resistant idipathic recurrent pericarditis were fllwed fr an average f 8.3 years: During fllw-up in in 10% f cases a new diagnsis f systemic inflammatry disease (namely rheumatid arthritis and Sjgren s syndrme) was established. Key message Idipathic recurrent pericarditis is nt necessarily a life-lng diagnsis Brucat A et al. Am J Cardil 2006;98:

25 Cncerns Unfrtunately, there are nly few RCTs and prspective studies and thus mst recmmendatins have been based n Task Frce cnsensus (LOE C). 135 recmmendatins Level f evidence A Level f evidence B Level f evidence C 6 (5%) 30* (22%) 99 (73%) *17 recmmendatins cncern neplastic pericarditis

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27 Systematic review f published cases with IVIG administratin in recurrent pericarditis Ttal number f patients *30 (21 males) Fllw-up 19.5 mnths Disease duratin 315 days Number f recurrences befre IVIG 3 Time t sterids withdrawal (mnths) *5.7 (16.6% are still n sterids) Time t REC 5 mnths Pts free f recurrences 73.3% *Data are presented as median values. Imazi M, Lazars G, et al. J Cardivasc Med 2015, In press.

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