Postcardiac injury syndrome (part II)

Abstract

Summary

A 58-year-old man had undergone 2-vessel off-pump coronary artery bypass surgery (OPCAB), 1 month before he was admitted into the hospital with cardiac tamponade due to pericarditis. Postcardiac injury syndrome (PCIS) was diagnosed. In spite of receiving anti-inflammatory treatment, the patient developed relapsing PCIS.

Part II

Answers to the questions

Our case was a 58-year-old man who had undergone 2-vessel off-pump coronary artery bypass surgery (OPCAB), 1 month before he was admitted into the hospital with cardiac tamponade due to the postcardiac injury syndrome.

Postcardiac injury syndrome (PCIS) was described by William Dressler in the middle of the last century. He observed the occurrence of pericarditis accompanied by fever, elevated inflammatory markers, and pleural exudate, occurring within several days/weeks after myocardial infarction (postmyocardial infarction syndrome [PMIS], Dressler syndrome). He described the symptoms as being nagging, yet associated with a good prognosis. He proposed an auto-aggression mechanism as a putative cause.

In addition, PCIS comprises: a) postcommissurotomy syndrome (PCS), described in 1952 by Janton, and in 1953 by Soloff’s group, occurring after the surgical treatment of mitral stenosis, and b) postpericardiotomy syndrome (PPS), described by Ito et al, as a consequence of surgical treatment of congenital heart disease.

Similar symptoms have been reported to occur after other cardio-surgical procedures (eg, valve replacement, correction of congenital heart defects, coronary artery bypass graft [CABG], heart injuries, pulmonary embolism, percutaneous coronary interventions, ablation therapy of arrhythmias, and implantation of the pacemakers) [1–4].

PCIS occurs within several days to weeks after surgery or myocardial infarction, with frequency ranging from 10% to 40% [5,8]. However, PPS is more frequent after valve replacement; on the other hand, in the case of Dressler syndrome, the frequency falls to 5%. At present, there is a trend of decreasing frequency of Dressler syndrome because of the effective aggressive treatment of acute coronary syndromes [5,8]. PCIS occurs significantly more often in younger patients (mean age 66+/−12 years) [8]. In the period preceding PCIS there may occur elevated body temperature, otherwise there are no specific symptoms. The diagnosis of PCIS is based on clinical evaluation and there is a lack of specific laboratory tests.

PCIS is the most often characterized by a benign course with mildly elevated body temperature (54% of patients), malaise, and muscle and joint aches. In addition, patients may suffer from chest pain increasing upon deep breathing or swallowing (56%), or dyspnea (57%) [5,8]. On physical examination, there may be symptoms of pericarditis, such as pericardial friction, or silent heart tones, or symptoms of pleuritis, including loss of breath sounds, and/or pleural friction (86% of patients). The aforementioned symptoms are accompanied by specific features on chest X-ray examination in 79% of patients. The radiologic findings may precede the occurrence of complaints by up to 2 days, or they may accompany or follow the occurrence of complaints [5]. The pericarditis generally is confirmed by echocardiography evaluation. On laboratory tests there are increased erythrocyte sedimentation rate (ESR) (74%), leukocytosis (49%) and eosinophilia [5,8].

Question

2: What is the differential diagnosis of PCIS?

Differential diagnosis should include other common causes of fever or chest pain associated with the surgery such as infection, postperfusion syndrome, and ”40-day postoperative fever” (CMV infection). In addition, conditions such as acute coronary syndrome, heart failure, and pulmonary embolism should be excluded.

Question

3: What is the prognosis of PCIS?

PCIS tends to self-heal, but recurrences are possible, even after 6 to 12 months post-surgery. In Dressler syndrome, recurrences are more common; they usually occur within a year after myocardial infarction, and last for 1–2 weeks. The rare, but most severe, complications of PPS are cardiac tamponade (2%), pericarditis constrictiva (0.2%), and aorto-coronary graft closure [5,8]. The known risk factors of PPS include young age, corticosteroid therapy, or medical history of pericarditis [5,8].

Question

4: What is the pathogenesis of PCIS?

The cause of PPS is not completely understood. Currently, an autoimmune mechanism, with the involvement of both cellular and humoral immune responses, is postulated.

PPS can be initiated by mesothelial injury and the presence of blood within the pericardial space, which, in turn, are thought to initiate inflammatory response. The involvement of the immune system is consistent with: a) the delayed onset of the symptoms after surgery or myocardial infarction; b) dramatic improvement after anti-inflammatory treatment; c) the tendency to recur, often associated with the discontinuation of steroid administration; and d) lack of correlation between the magnitude of symptoms and the level of myocardial damage markers [5–7].

It was hypothesized that the surgery leads to the release and presentation of cardiac antigens, leading to the production of various cardiac-specific or unspecific antibodies. As a result, the formation of immune complexes can be detected in the pericardium, lungs, and pleura (eg, in the vicinity of the ”injury” site. The immune complexes may be responsible for the initiation of the inflammatory reactions, via complement system activation, leading to the occurrence of specific symptoms [6,7].

As early as 1964, Van der Geld described the occurrence of specific antibodies directed against cardiac tissues (AHA) in the serum of the majority of PPS patients. This was confirmed by McCabe et al, who found a correlation between the high AHA titer and the occurrence of PCIS [7]. Interestingly, in contrast to PCIS patients, those having pericarditis due to other-than-injury causes had not only lower AHA titers, but also a significant cross-reactivity of the antibodies with streptococcal antigens [7]. There was no AHA in the pericardial exudate.

Other authors demonstrated frequent presence of autoantibodies against actin, myosin, troponins I and T, tropomyosin, BCKD-E2, sarcolemma and endothelium, as well as mild elevation of antinuclear antibodies, in PCIS patients [6,7]. It was reported that the increased level of antinuclear antibodies found before the surgery may be associated with more severe and protracted course of PCIS; however, these findings are controversial [7].

On the other hand, increased AHA titers are also found in patients undergoing cardiac surgeries without subsequent PCIS [7]. Nevertheless, since the increased AHA levels occur in all PCIS patients, the antibodies can be regarded as markers of PCIS, although some authors consider only high AHA titers as being of diagnostic value [6,7].

Consistent with the proposed role of immune complexes, decreased level of complement factors (C3 and C4) accompanied by elevated AHA (1:80 and more) and the presence of antigen-antibody complexes was found in pleural effusions from PPS patients.

A possibility of the involvement of cellular immunity was also investigated. Accordingly, increased level of cytotoxic T lymphocytes was found in patients with PCIS. In addition, in children having PCIS after heart transplantation, increased CD4+/CD25+ helper cells were detected both before, and 2 weeks after, PPCS diagnosis [7].

The theories of infectious causes of PCIS, such as a viral infection of the myocardial injury site causing systemic autoimmune reaction, or reactivation of rheumatic fever, have not been confirmed [7].

Question

5: What are the treatment options?

The treatment of PCIS is currently based mainly on high doses of non-steroidal anti-inflammatory drugs (NSAIDs) (ie, diclofenac, ibuprofen) and diuretics [5,8,9].

As an alternative treatment approach, and the best treatment for primary and secondary (recurrent pericarditis) prevention, colchicine is recommended (COPPS study) [9,10].

In case of lack of improvement after NSAIDs or colchicine, treatment with corticosteroids in moderately high doses (eg, prednisone 0.5–1 mg/kg, average 60 mg daily) together with NSAIDs/colchicine, or in monotherapy, is indicated [5,9]. However, systemic corticosteroids improve clinical recovery and reduce complications, but they increase incidence of relapses after their discontinuation.

In case of massive pericardial exudate and tamponade, pericardiocentesis is performed.

There have been a few reports on the positive effect of methotrexate or intravenous immunoglobulin (IVIG) treatment in cases of the refractory syndromes.

For recurrent effusions for which repeated pericardiocentesis is unsuccessful, the percutaneous balloon pericardial window formation is indicated, as well as the administration of sclerosing agents (eg, minocycline), or surgical drainage (localized effusion) [9].

Surgical pericardiectomy before calcification of the pericardium, the palliative treatment of constrictive pericarditis, is aimed at relief of fluid overload [9].

Conclusions

• Postcardiac injury syndrome (PCIS) comprises postpericardiotomy syndrome (PPS), postmyocardial infarction (Dressler) syndrome (PMIS), and postcommissurotomy syndrome (PCS).

• Diagnosis is based on clinical criteria – the occurrence within about a week after (peri)cardiac injury or myocardial infarction, and abnormal echocardiography and chest X-ray findings.

• The cause of PPS is not completely understood. Currently, an autoimmune mechanism with the involvement of both cellular and humoral immune responses is postulated.

• The treatment is based on NSAIDs or colchicine and, rarely, corticosteroid administration.

• The prognosis is usually favorable; however, recurrences may occur.