Postpericardiotomy syndrome is a challenging condition because it encompasses the clinical spectrum from innocuous asymptomatic sign (e.g., friction rub, small pleural or pericardial effusion) to life threatening inflammatory condition (e.g., systemic inflammatory state with cardiac tamponade). The recently published population-based Finland postpericardiotomy syndrome study (FinPPS) by Lehto and colleagues provides some insight into the issues at hand¹. A good place to start the review of the article would be in the context of the Centers for Disease Control and Prevention's 5 W's for characterizing epidemiologic events: what, who, where, when, and why/how².

What: an inflammatory response following pericardiotomy characterized by the presence of at least 2 of the following relatively standardized clinical criteria: fever without alternative causes, pleuritic chest pain, friction rub, and evidence of new or worsening pleural or pericardial effusion^{1, 3}.

Who: consecutive series of 688 predominantly elderly (median age 67 years), presumably Norwegian, men (78%) operated with isolated coronary artery bypass graft operation. No patient received preoperative colchicine during the index operation.

Where: catchment area of the Turku University Hospital, the Turku City Hospital, and the Satakunta Central Hospital, Finland.

When: operations performed 2008 to 2010.

Why/how: retrospective identification of the stated "what" clinical criteria from patient medical record review.

Lehto and colleagues reported a clinically evident diagnosis of postpericardiotomy syndrome in 61 patients (8.9%). The diagnosis was based upon an assortment of clinical findings including a pericardial friction rub that was present in only 6.9% of patients, pleuritic chest pain in 20%, and fever in 41%; whereas pericardial effusion was present in 93% of patients, and new or worsening pleural effusion or cardiac silhouette enlargement in 93%. The variability in these rates is quite similar to what was reported by Alaires and colleagues from the Cleveland Clinic in their recent series of 239 patients with postpericardiotomy syndrome⁴.

The 8.9% incidence of postpericardiotomy syndrome in the present study was much less than the 29.4% reported by Imazio and colleagues in the placebo group of the prospective Colchicine for Prevention of Postpericardiotomy Syndrome and Postoperative Atrial Fibrillation (COPPS-2) trial⁵. Why the marked difference? The group from Finland suggests that diagnosis in prospective studies such as the COPPS-2 trial is more sensitive; and, that the present FinPPS study implicates many of the diagnoses in the COPPS-2 study were clinically irrelevant.

Is there support in the implication from Lehto and colleagues about the clinically irrelevant nature of the COPPS-2 prospectively arrived at diagnoses of postpericardiotomy syndrome? Analysis of the data would suggest so—thoracentesis or pericardiocentesis was performed in 7.2% of the patients in the prospective COPPS-2 study, while the procedures were performed in 23% of the patients in the present Finnish study^{1, 5}. It would appear that Lehto and colleagues make a valid argument, and that the denominator of cases with clinically insignificant postpericardiotomy syndrome (as evidenced by no need of pleural or pericardial puncture) is much larger in the prospective COPPS-2 study.

Lehto and colleagues state in their "real world" study that the course of postpericardiotomy syndrome requiring medical attention was mainly benign. They make the statement based on the 23% incidence of pericardial or pleural drainage performed. This may be an overstatement as patients may not necessarily consider a drainage procedure "benign". The statement also ignores the 38% incidence of relapse as defined by worsening of pericardial or pleural effusion while on medication or after withdrawal of medication. And nothing is said of the development of constrictive pericarditis, which was reported by Alraies and colleagues to have occurred in 41% of the patients treated with a procedure intervention less than 12 months after the diagnosis of postpericardiotomy syndrome.

Lehto and colleagues found that red blood cell transfusion was predictive of postpericardiotomy syndrome, but not of relapse. To be specific, in multivariate analysis, 1 or more red blood cell units transfused had a Hazard ratio of 1.9, 95% confidence interval of 1.1-3.2, and a P value of .017. The finding is of importance, especially when taken in the context of the association of blood transfusion with worse outcomes and increased medical costs⁶. Surgeons may now add lower risk of postpericardiotomy syndrome to the list of beneficial effects of a blood conservation strategy.

There are 3 important ideas to take away from this article by Lehto and colleagues: 1) clinically significant postpericardiotomy syndrome is probably less common than previously reported in the literature; 2) the course of postpericardiotomy syndrome is not benign, with intervention, relapse, and constriction being an unwelcome series of untoward events; and 3) blood conservation does more than just conserve blood, it may be protective against postpericardiotomy syndrome.

References

1. Lehto J, Gunn J, Karjalainen P, Airaksinen J, and Kiviniemi T. Incidence and risk factors of postpericardiotomy syndrome requiring medical attention: the Finland postpericardiotomy syndrome study. J Thorac Cardiovasc Surg 2015;149:1324-9.
2. Principles of Epidemiology in Public Health Practice, Third Edition: An introduction to applied epidemiology and biostatistics. http://www.cdc.gov/ophss/csels/dsepd/ss1978/lesson1/section1.html. Accessed 11 Oct 2015.
3. Imazio M, Brucato A, Ferrazzi P, Spodick DG, and Adler Y. Post pericardiotomy syndrome: a proposal for diagnostic criteria. J Cardiovasc Med (Hagerstown) 2013;14:351-3.
4. Alraies MC, Al Jaroudi W, Shabrang C, Yarmohammadi H, Klein AL, and Tamarappoo BK. Clinical features associated with adverse events in patients with post-pericardiotomy syndrome following cardiac surgery. Am J Cardiol 2014;114:1426-30.
5. Imazio M, Brucato A, Ferrazzi P, Pullara A, Adler Y, Barosi A, et al. Colchicine for Prevention of Postpericardiotomy Syndrome and Postoperative Atrial Fibrillation: The COPPS-2 Randomized Clinical trial. JAMA 2014;312:1016-23.
6. Yaffee DW, Smith DE, Ursomanno PA, Hill FT, Galloway AC, DeAnda A, et al. Management of blood transfusion in aortic valve surgery: impact of a blood conservation strategy. Ann Thorac Surg 2014; 97:95-101.

Keywords: Aged, Atrial Fibrillation, Bloodless Medical and Surgical Procedures, Cardiac Tamponade, Chest Pain, Colchicine, Confidence Intervals, Constriction, Coronary Artery Bypass, Drainage, Erythrocyte Transfusion, Erythrocytes, Friction, Heart Diseases, Hospitals, University, Hospitals, Urban, Incidence, Medical Records, Multivariate Analysis, Pericardial Effusion, Pericardiectomy, Pericardiocentesis, Pericarditis, Constrictive, Pleural Effusion, Postpericardiotomy Syndrome, Prospective Studies, Recurrence, Retrospective Studies, Surgeons

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