Post-cardiac injury syndromes

INTRODUCTION — 

Pericarditis with or without a pericardial effusion resulting from injury of the pericardium constitutes the post-cardiac injury syndrome. The principal conditions considered under this rubric are:

●Post-myocardial infarction (MI) (Dressler syndrome)

●Postpericardiotomy syndrome

●Posttraumatic pericarditis (caused by traumatic or iatrogenic injury)

The clinical presentation, diagnostic evaluation, and treatment of post-cardiac injury syndromes will be reviewed here. Related topics are discussed separately:

●(See "Acute pericarditis: Clinical presentation and diagnosis" and "Acute pericarditis: Treatment and prognosis".)

●(See "Pericardial effusion: Approach to diagnosis" and "Pericardial effusion: Approach to management" and "Cardiac tamponade".)

●(See "Constrictive pericarditis: Clinical features and causes" and "Constrictive pericarditis: Diagnostic evaluation" and "Constrictive pericarditis: Management and prognosis".)

●(See "Etiology of pericardial disease".)

DEFINITION — 

Post-cardiac injury syndromes are conditions in which inflammatory pericardial disease occurs [1,2]:

●After pericardial and/or myocardial injury (caused by MI, trauma, surgical pericardiotomy, or percutaneous cardiac intervention). (See 'Causes and their frequencies' below.)

and

●With a latent period (ranging from days to months) between the injury and the development of pericarditis with or without pericardial effusion. The duration of the latent period varies widely among patients.

CAUSES AND THEIR FREQUENCIES

Post-myocardial infarction — A post-cardiac injury syndrome may occur one week to three months after MI [1]. This syndrome was first described by Dressler in 1956 [3,4].

Dressler syndrome differs from early post-MI pericarditis and/or effusion which occurs within a few days after transmural MI as a result of involvement of the epicardial surface or rupture of the free wall of the left ventricle. These conditions are discussed separately. (See 'Differential diagnosis' below and "Pericardial complications of myocardial infarction", section on 'Peri-infarction pericarditis' and "Acute myocardial infarction: Mechanical complications", section on 'Rupture of the left ventricular free wall'.)

Although data are limited, the frequency of post-cardiac injury syndrome after MI appears to be low, particularly among patients with MI treated with early myocardial reperfusion.

●In studies performed prior to the use of widespread early reperfusion therapy, rates of post-MI pericarditis ranged from 3 percent (of 1809 patients) to none (of 282 patients) [5,6].

●With early reperfusion therapy for MI, post-MI cardiac injury with pericarditis appears to have largely disappeared, perhaps due to a decrease in size and transmural extent of most MIs [7]. In a cohort of 201 consecutive patients with acute MI treated with fibrinolysis, only one patient developed post-cardiac injury syndrome, and this patient had no evidence of reperfusion [8]. In a study of 743 patients with MI treated with primary percutaneous coronary intervention, late post-MI pericarditis was identified in only 1 patient (0.1 percent) [9].

Postpericardiotomy syndrome — The term "postpericardiotomy syndrome" replaced the prior term "postcardiotomy syndrome" after it was discovered that the syndrome can occur after the pericardium is opened even if no other cardiac structures are involved (eg, after surgery for bronchogenic lung carcinoma).

Limited data are available on rates of postpericardiotomy syndrome. Differences in rates are likely related to differing thresholds for reporting the condition as well as differing types and combinations of cardiothoracic procedures performed:

●Among a cohort of 28,761 patients in Finland undergoing only one type of surgery (coronary artery bypass graft, valve, or aortic surgery), 493 patients (1.7 percent) developed post-cardiac injury syndrome requiring hospital admission or contributing to mortality [10]. Thus, this study identified only severe cases of the syndrome. The risk appeared higher in patients undergoing valvular or aortic surgery, compared with patients undergoing coronary artery bypass grafting.

●In a much smaller cohort of 360 consecutive patients undergoing cardiac surgery, 54 patients (15 percent) developed post-cardiac injury syndrome [11]. In this study, 32 percent of patients underwent coronary artery bypass graft surgery plus another procedure such as valve surgery. Patients with postpericardiotomy syndrome more frequently underwent more than one type of surgery during each procedure (31.5 versus 16.3 percent) or underwent pleural incision (66.7 versus 34.6 percent).

Risk factors for pericardial effusions after cardiac surgery appear to be different for early (within seven days) pericardial effusions versus late effusions. This was illustrated in a registry of patients with significant pericardial effusions after cardiothoracic surgery who underwent pericardiocentesis guided by echocardiography [12]. Postpericardiotomy syndrome was an important contributing factor in approximately one-third of late effusions. Anticoagulant therapy was considered to be a contributing factor for early (<7 days) and late effusions. (See 'Differential diagnosis' below.)

Posttraumautic pericarditis

Blunt or sharp trauma — Patients may develop pericarditis following traumatic pericardial and/or myocardial injury. Pericardial injury may result from blunt trauma (eg, steering wheel contact in an automobile accident or a fall from a significant height) or sharp penetrating trauma (eg, injury inflicted by a knife or bullet).

The acute management of patients with traumatic chest injuries is discussed in detail separately. (See "Initial evaluation and management of blunt thoracic trauma in adults" and "Initial evaluation and management of penetrating thoracic trauma in adults" and "Initial evaluation and management of blunt cardiac injury".)

Iatrogenic injury — Post-cardiac injury syndrome may also occur after iatrogenic pericardial and/or myocardial injury (eg, associated with percutaneous coronary intervention, insertion of a pacing or defibrillator lead, percutaneous valvular procedures, or catheter radiofrequency ablation) [13]. In these iatrogenic cases, the provoking cardiac injury is sometimes surprisingly minor.

PATHOPHYSIOLOGY — 

The post-cardiac injury syndrome appears to be initiated by the combination of damage to mesothelial pericardial cells and blood in the pericardial space [2,14]. The initial injury is thought to trigger an immune process. The following observations are compatible with this hypothesis:

●The discrete latent period from cardiac injury to the clinical onset of post-cardiac injury syndrome.

●Coexistent pleural effusion and/or pulmonary infiltrates in some cases.

●Studies in patients undergoing cardiac surgery have found a statistically significant correlation between the postoperative to preoperative ratios of antiactin and antimyosin antibodies and the clinical occurrence of post-cardiac injury syndrome [15,16].

●The generally excellent response to antiinflammatory therapy, and occasional relapses after steroid withdrawal [14].

The following immune responses to cardiac injury have been proposed:

Inflammasome — Studies suggest a pathogenic role for NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) inflammasome and its effects on production of interleukin (IL)-1 cytokines in pericarditis syndromes [17-19].

Immune complexes — The role of immune complexes in patients who develop the postpericardiotomy syndrome is uncertain. It has been proposed that cardiac injury releases cardiac antigens which stimulate antibody production. The immune complexes that are generated are then deposited in the pericardium, pleura, and lungs, eliciting an inflammatory response [14]. The initial prospective study that identified immune complexes in the post-cardiac injury syndrome compared children who did and did not develop a postpericardiotomy syndrome after cardiac surgery [20]. Those who developed postpericardiotomy syndrome had increased antimyocardial antibodies. Several subsequent studies have demonstrated the presence of antimyocardial antibodies in patients who develop the postpericardiotomy syndrome [15,16,21]. Antimyocardial antibodies in pleural fluid have also been reported [22,23].

However, the significance of antimyocardial antibodies and their relation to the severity of myocardial injury is unclear [21]. There is some evidence that antiheart antibodies may be an epiphenomenon. In a prospective study of 20 surgical patients in whom serum was sampled for antiheart antibodies before and periodically after elective coronary artery bypass surgery [24], antiheart antibodies were absent in all patients on the day before surgery. Three patients developed postpericardiotomy syndrome. All were seronegative at the time of diagnosis, but they became seropositive within the ensuing 14 days.

Cell-mediated immunity — The post-cardiac injury syndrome has also been described in children following orthotopic cardiac transplant [25]. The immunologic features suggest a role for cell-mediated immune responses in this setting.

CLINICAL FEATURES — 

Patients who develop post-cardiac injury syndrome present with symptoms and signs like those seen in patients with other causes of acute pericarditis (with or without pericardial effusion) after a latent period following pericardial or myocardial injury. (See "Acute pericarditis: Clinical presentation and diagnosis" and "Pericardial effusion: Approach to diagnosis".)

The clinical features of the post-cardiac injury syndrome include [2]:

●Symptoms and signs

•Fever without other cause.

•Chest pain which is pleuritic (worsened with deep breaths) or pericarditic (anterior pleuritic chest pain which diminishes when the patient sits up and leans forward).

•Pericardial and/or pleural friction rub (movie 1).

A pericardial or pleural friction rub should be distinguished from the mediastinal friction rub or "crunch" which is frequently appreciated in the first few days after cardiac surgery. This early postoperative finding caused by surgical emphysema is characterized by a substernal, crunching, rasping sound that is synchronous with the heartbeat and usually associated with palpable chest wall subcutaneous emphysema. (See "Auscultation of heart sounds", section on 'Pericardial friction rub and other adventitious sounds'.)

●Test findings

•Electrocardiogram (ECG) – ECG changes classically include diffuse ST-segment elevation in association with PR depression, although often absent or masked by other ECG findings (waveform 1). (See 'Electrocardiogram' below.)

•Laboratory tests – Leukocytosis and elevated markers of inflammation (erythrocyte sedimentation rate [ESR] and/or C-reactive protein [CRP]). (See 'Laboratory testing' below.)

•Imaging – On chest radiograph, a pleural effusion may be identified with or without a pulmonary infiltrate. (See 'Chest radiograph' below.)

An echocardiogram may or may not identify a pericardial effusion. Cardiac tamponade is rare in this setting. (See 'Echocardiogram' below.)

The clinical features of post-cardiac injury syndrome were illustrated by the above-cited series of patients with postpericardiotomy syndrome [11]:

●The most frequent signs and symptoms in this cohort were pleuritic chest pain (56 percent) and fever (54 percent).

●Common findings on physical examination and diagnostic testing included:

•Pericardial rub (32 percent)

•ECG changes (24 percent)

•Elevated CRP or ESR (74 percent)

•Pericardial effusion (89 percent) with rare cardiac tamponade (2 percent)

EVALUATION

When to suspect post-cardiac injury syndrome — The diagnosis of post-cardiac injury syndrome is typically suspected based upon the characteristic clinical picture of pleuritic chest pain and/or fever developing one week to three months following an MI, cardiothoracic surgery with pericardiotomy, chest trauma, or percutaneous cardiac intervention. (See 'Clinical features' above and 'Causes and their frequencies' above.)

The diagnostic evaluation of all patients with suspected post-cardiac injury syndrome includes laboratory testing, a 12-lead ECG, a chest radiograph, and an echocardiogram.

Laboratory testing — Patients with suspected post-cardiac injury syndrome should undergo laboratory testing including complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and troponin I or T. Most but not all patients will have an elevated white blood cell count and inflammatory markers (CRP and ESR).

Electrocardiogram — A 12-lead ECG should be performed in all patients with suspected post-cardiac injury syndrome, although it is difficult to make the diagnosis based on ECG findings alone. The ECG is usually abnormal following an MI and after various types of cardiac surgery for a variety of reasons (eg, ischemic ST-segment or T-wave changes, developing Q waves, various nonspecific ST-T abnormalities, postoperative epicardial pacing, etc). However, when ECG changes suggestive of pericarditis are present (ie, diffuse ST-segment elevation in association with PR depression) and represent a change from the patient's baseline ECG, this is highly suggestive of post-cardiac injury syndrome. (See "Acute pericarditis: Clinical presentation and diagnosis", section on 'Electrocardiogram'.)

Imaging

Chest radiograph — A chest radiograph should be performed in all patients with suspected post-cardiac injury syndrome. Although it is not possible to definitively make the diagnosis based on radiographic findings alone, the chest radiograph is helpful in excluding other pathology (eg, pneumonia, pneumothorax, etc).

The chest radiograph in a patient who has developed a postoperative pericardial effusion often reveals an increase in heart size (particularly when compared with a baseline radiograph). When this is seen, the presence of an effusion should be promptly confirmed or excluded by echocardiography. In a significant minority of patients, the chest radiograph also reveals a pleural effusion, usually unilateral, although this may become apparent only on a subsequent radiograph. Pulmonary infiltrates are occasionally seen. (See "Evaluation and management of pleural effusions following cardiac surgery".)

Echocardiogram — All patients with suspected post-cardiac injury syndrome should be evaluated with echocardiography. In most instances, transthoracic echocardiography is satisfactory, but transesophageal echocardiography may be required in patients with difficult or limited imaging windows (as can frequently occur postoperatively) in whom the transthoracic study is nondiagnostic. The echocardiogram is used to determine the presence or absence of pericardial effusion, to quantify the size of an effusion, and to detect the various echocardiographic signs that are used to support or refute the presence of cardiac tamponade. (See "Pericardial effusion: Approach to diagnosis", section on 'Echocardiography'.)

Additional imaging — When echocardiographic imaging is suboptimal or nondiagnostic, cardiovascular magnetic resonance (CMR) imaging or cardiac computed tomography (CT) is helpful [26]. CMR enables detection of pericardial inflammation and thickening and myocardial injury or infarction. Cardiac CT enables detection of pericardial thickening, calcification, and effusion. (See "Clinical utility of cardiovascular magnetic resonance imaging" and "Cardiac imaging with computed tomography and magnetic resonance in the adult".)

DIAGNOSIS — 

Abnormalities seen on laboratory testing (leukocytosis, elevated erythrocyte sedimentation rate, elevated C-reactive protein), ECG (diffuse ST-segment elevation in association with PR depression), chest radiograph (increased heart size, pleural effusion), and echocardiogram (pericardial effusion) are supportive, but none of these features are individually specific enough to definitively make the diagnosis.

In the setting of one of the causes of post-cardiac injury syndromes, the combination of a pericardial friction rub and ECG findings typical of pericarditis strongly supports the diagnosis, and the diagnosis is also strongly supported if an echocardiogram reveals a pericardial effusion at a time when effusions are no longer routine (nontrivial effusions are uncommon after 7 to 10 days postinjury). (See 'Differential diagnosis' below.)

DIFFERENTIAL DIAGNOSIS — 

Post-cardiac injury syndrome should be distinguished from other clinical conditions that result in fever, pleuritic chest pain, pericardial effusion, and/or auscultatory findings similar to a pericardial rub. In most instances, post-cardiac injury syndrome can be distinguished from these other entities by the clinical scenario although symptoms and signs may be similar. In some cases, post-cardiac injury syndrome occurs concurrently with conditions with overlapping symptoms or signs (eg, rib fractures or pneumothorax following chest trauma).

The following conditions should be distinguished from post-cardiac injury syndrome:

●Complications of MI or its treatment – In the setting of an MI, hemopericardium is rarely caused by rupture of the left ventricular free wall or coronary artery perforation during percutaneous coronary intervention. Myocardial rupture generally occurs within the first two weeks after MI and usually causes rapid and severe hemodynamic compromise. (See "Acute myocardial infarction: Mechanical complications" and "Periprocedural complications of percutaneous coronary intervention", section on 'Perforation'.)

●Complications of trauma or percutaneous interventions – Complications of trauma or percutaneous interventions may present with symptoms and signs that are generally earlier than but similar to those of post-cardiac injury.

For example, blunt trauma is often associated with hemothorax, pneumothorax, pleural effusion, pulmonary contusion, or fractures that can be identified on chest radiograph. (See "Initial evaluation and management of blunt thoracic trauma in adults".)

Chylopericardium is a rare complication of injury to the thoracic duct caused by trauma or thoracic surgery. It tends to occur in children who have had extensive surgical treatment for complex congenital malformations. However, any operation involving dissection of the ascending aorta and the main pulmonary artery risks injury to the right efferent lymphatic trunk and subsequent chylopericardium [27]. (See "Chylopericardium and cholesterol pericarditis".)

●Postoperative complications – A number of complications of cardiothoracic surgery (such as hemothorax, pericardial hematoma, and subcutaneous emphysema) present earlier than postpericardiotomy syndrome but with similar symptoms and signs.

Serial echocardiographic studies have shown that postoperative pericardial effusion following cardiac surgery is considerably more common than is clinically obvious, occurring in as many as 85 percent of patients [28]. The effusion is usually present by the second postoperative day but may not occur until day 10. In most cases, the effusion reaches its maximal size by approximately the 10th postoperative day and is followed by gradual resolution. Because postoperative pericardial effusions are so common and most are benign, it is generally not necessary to perform routine postoperative echocardiography in the absence of other clinical features that suggest pericardial disease.

●Pleuritis or pleuropericarditis – Infectious causes (such as pneumonia) are typically associated with sputum production, while noninfectious causes such as malignancy may have other associated systemic symptoms (eg, weight loss, night sweats, signs of the primary malignancy, etc). Chest imaging (eg, chest radiograph and chest CT) is used to identify causes of pleural disease. (See "Outpatient evaluation of the adult with chest pain" and "Pneumococcal pneumonia in patients requiring hospitalization".)

●Pulmonary embolism – Patients with pulmonary embolism will often have an associated risk for thromboembolism (eg, surgery, immobility, malignancy) and are typically hypoxic. The considerable overlap in clinical presentation between post-cardiac injury syndrome and pulmonary embolism with associated pulmonary infarction usually requires CT angiography to distinguish between the two entities. Pulmonary embolism is typically diagnosed when filling defects are seen on CT pulmonary angiography. (See "Clinical presentation and diagnostic evaluation of the nonpregnant adult with suspected acute pulmonary embolism".)

●Esophageal rupture (Boerhaave syndrome) – Typically this occurs following vomiting, prolonged coughing, childbirth, or weightlifting with straining. Free air within the mediastinum or peritoneum on a chest radiograph is suggestive of esophageal rupture. (See "Boerhaave syndrome: Effort rupture of the esophagus".)

●Pneumothorax – Primary pneumothorax typically occurs in younger patients (less than 40 years of age), while secondary pneumothorax is typically iatrogenic (eg, following central venous catheter placement or bronchoscopy) or traumatic (eg, rib fractures). In most instances this should be visible on the chest radiograph. (See "Clinical presentation and diagnosis of pneumothorax" and "Pneumothorax in adults: Epidemiology and etiology".)

●Systemic autoimmune disorders (eg, systemic lupus erythematosus) – Typically, patients have other signs of systemic involvement by the systemic autoimmune disorder (eg, musculoskeletal symptoms, rash, kidney disease, etc). Laboratory testing for systemic autoimmune diseases may be required to differentiate these from other causes of pleuritis or pleuropericarditis. (See "Pericardial involvement in systemic autoimmune diseases" and "Pulmonary manifestations of systemic lupus erythematosus in adults".)

PREVENTION

Colchicine

For cardiac surgery — For most patients undergoing cardiac surgery, we suggest postoperative prophylactic treatment with colchicine rather than expectant management. We treat with a 30-day course of colchicine beginning one to three days following surgery (0.5 or 0.6 mg twice daily for patients ≥70 kg, 0.5 or 0.6 mg daily for those <70 kg).

Our approach to prophylactic colchicine use in this population places a higher value on the reduction in post-cardiac injury syndrome and its potential complications rather than the risk of medication-related side effects. Patients who place a higher value on the avoidance of additional medications and potential colchicine-related side effects may opt to not use colchicine, in which case the treating clinician should emphasize with the patient the importance of early recognition of potential symptoms and treatment should symptoms arise.

In the two largest randomized, double-blind trials comparing prophylactic colchicine with placebo, colchicine reduced the incidence of the postpericardiotomy syndrome:

●In the double-blind multicenter Colchicine for the Prevention of Post-pericardiotomy Syndrome (COPPS) study, 360 cardiac surgery patients were randomly assigned on postoperative day three to colchicine (1 mg twice daily on day 1, then 0.5 mg twice daily for patients ≥70 kg; halved doses for patients <70 kg or intolerant of the higher doses) or placebo administered for 30 days [29]. Colchicine significantly reduced the occurrence of the primary endpoint of postpericardiotomy syndrome at 12 months (9 versus 21 percent with placebo; relative risk [RR] 0.42, 95% CI 0.24-0.73). The rate of side effects, primarily related to gastrointestinal intolerance, was similar in the colchicine and placebo groups.

●In the double-blind multicenter COPPS-2 trial, 360 cardiac surgery patients were randomly assigned to receive colchicine (0.5 mg twice daily for patients ≥70 kg, 0.5 mg daily for those <70 kg) or placebo beginning 48 to 72 hours prior to surgery and continued for one month postoperatively [30]. Colchicine significantly reduced the occurrence of the primary endpoint of postpericardiotomy syndrome at three months (19 versus 29 percent with placebo; RR 0.66, 95% CI 0.45-0.96). However, unlike in the original COPPS trial, treatment with colchicine was associated with significantly more adverse effects, primarily gastrointestinal (20 versus 12 percent with placebo; RR 1.71, 95% CI 1.04-2,82).

While randomized trials [29-31] have found that colchicine reduced the incidence of postpericardiotomy syndrome, the increase in adverse effects seen in trials including COPPS-2 is somewhat concerning [30,31]. In particular, diarrhea, the main gastrointestinal side effect of colchicine, is problematic in patients early after cardiac surgery and may limit prophylactic colchicine use. Side effects appear to be lower when colchicine is started postoperatively rather than preoperatively.

Not established for AF ablation — For patients undergoing atrial fibrillation (AF) ablation, we suggest not administering prophylactic colchicine. The efficacy of prophylactic colchicine for preventing acute pericarditis following catheter ablation of AF has not been established.

No benefit from prophylactic colchicine was identified in a meta-analysis of five studies with a total of 1592 patients undergoing catheter ablation for AF (two randomized trials, one prospective observational study, and two retrospective studies) [32]. Pooled results revealed no significant decrease in rates of postablation pericarditis (odds ratio [OR] 0.67, 95% CI 0.26–1.72) or AF recurrence (OR 0.74, 95% CI 0.48–1.12) with prophylactic colchicine compared with placebo or no colchicine, but there was significant heterogeneity among the studies, particularly for pericarditis. Gastrointestinal side effects were higher in patients treated with colchicine (OR 4.84, 95% CI 2.58–9.05).

A possible benefit from prophylactic colchicine was suggested by an observational study (which was the largest study included in the above-cited meta-analysis) [33]. Among 1075 patients undergoing catheter ablation for AF, the rate of postablation acute pericarditis was lowest in patients taking prophylactic pre- and postablation colchicine (0.3 mg twice daily from seven days before to one month postablation; 1.9 percent), higher in patients taking only postablation prophylactic colchicine (colchicine 0.3 mg twice daily for one month; 7.5 percent), and highest in patients taking no colchicine (17.5 percent). In the subpopulation of patients with baseline paroxysmal AF, the risk of recurrent AF at one-year follow-up was lower in the two groups of patients who had taken colchicine compared with the group that did not take colchicine (29.7 and 28 versus 38.8 percent). The rates of gastrointestinal side effects were similar in the groups with and without colchicine therapy.

Drainage of pericardial effusion — Observational studies suggest that surgical drainage of postpericardiotomy pericardial effusions (eg, by posterior pericardiectomy) may decrease the risk of early postoperative AF by decreasing pericardial inflammation [34].

Limited evidence suggests that draining postpericardiotomy pericardial effusions may reduce the risk of subsequent chronic constrictive pericarditis [35], but such an effect has not been established. Management and prevention of constrictive pericarditis is discussed separately. (See "Constrictive pericarditis: Management and prognosis".)

Glucocorticoid not effective — In contrast to colchicine, prophylactic glucocorticoid therapy in patients undergoing cardiac surgery appears to have no beneficial effect on post-cardiac injury syndrome [1,29,30,36-38]. In a single-center post hoc analysis of 822 patients from the DECS trial who underwent valvular surgery and received a one-time intraoperative dose of 1 mg/kg of dexamethasone (421 patients) or placebo (401 patients), there was no significant difference in the development of postpericardiotomy syndrome (13.5 versus 15.5 percent with placebo; RR 0.88, 95% CI 0.63-1.22); moreover, the incidence of a complicated postpericardiotomy syndrome (defined as the need to drain a pericardial or pleural effusion, or rehospitalization for a recurrence) was similar (3.8 versus 3.2 percent, respectively; RR 1.17, 95% CI 0.57-2.41) [38].

TREATMENT — 

Post-cardiac injury syndrome is generally responsive to antiinflammatory therapy similar to that used for acute pericarditis (nonsteroidal antiinflammatory drugs [NSAIDs], colchicine, and glucocorticoids), although there is a risk of recurrence. First-line treatment consists of NSAIDs, generally in combination with colchicine, although there are no randomized controlled trials of different dosing regimens. (See "Acute pericarditis: Treatment and prognosis" and 'Prognosis' below.)

Initial therapy — Initial management of post-cardiac injury syndrome is with a combination of an NSAID and colchicine, as for other causes of acute pericarditis (table 1).

NSAIDs — As for other types of acute pericarditis, NSAIDs are the primary treatment for all patients with post-cardiac injury syndrome, with the duration of treatment and tapering of medication based upon the persistence of symptoms (table 1). The 2015 European Society of Cardiology guidelines do not distinguish between aspirin or other NSAIDs (usually ibuprofen) with respect to efficacy and suggest that drug selection should be based on criteria other than efficacy (eg, likelihood of side effects, other aspirin indications) [1]. Two commonly used regimens are [39]:

●Aspirin – The dose of aspirin should be 750 to 1000 mg every six to eight hours, with gradual tapering of the total daily dose by 750 to 1000 mg every week for a treatment period of three to four weeks.

In pericarditis associated with an acute MI, aspirin is preferred, as nearly all patients post-MI will require aspirin for secondary prevention purposes. Aspirin may also be the first choice in other patients who have a concomitant indication for antiplatelet therapy. (See "Pericardial complications of myocardial infarction".)

●Ibuprofen – The dose of ibuprofen should be 600 to 800 mg every six to eight hours, with gradual tapering of the total daily dose by 400 to 800 mg every week for a treatment period of three to four weeks.

With any aspirin or NSAID regimen, gastrointestinal protection should be provided. (See "NSAIDs (including aspirin): Primary prevention of gastroduodenal toxicity".)

Colchicine — Colchicine is commonly included in the antiinflammatory regimen for treatment of post-cardiac injury syndrome, based upon the its effectiveness for other types of acute pericarditis (table 1), although there is limited data on its efficacy for post-cardiac injury syndrome [1]. In one single-center, retrospective study of 239 patients with post-cardiac injury syndrome following cardiac surgery in which 51 patients (21 percent) received colchicine as part of their treatment, patients treated with the combination of colchicine and an antiinflammatory drug were less likely to require intervention (ie, pericardiocentesis, pericardial window, pericardiectomy) for complications of post-cardiac injury syndrome (adjusted odds ratio 0.43, 95% CI 0.20-0.90) [40].

In contrast, the routine use of colchicine does not appear useful in the treatment of asymptomatic postoperative pericardial effusions [41]. In a double-blind randomized trial of 197 patients with asymptomatic moderate- to large-sized pericardial effusions at 7 to 30 days after surgery, both colchicine and placebo had similar effects on the effusion volume and the likelihood of late cardiac tamponade [42]. Similar findings were reported in a randomized trial in 149 patients with asymptomatic pericardial effusions (mild to moderate in size) identified by echocardiography three weeks after surgery, in which patients randomized to colchicine had similar outcomes to patients who received placebo [41]. Based on these findings we do not use colchicine in the treatment of asymptomatic postoperative pericardial effusions.

Follow-up — There is little consensus on the need for serial or follow-up studies, but most experts recheck inflammatory markers (CRP and ESR) following the resolution of symptoms (typically within one to two weeks) to ensure that the inflammation is resolving prior to tapering or discontinuing therapy, as for other types of acute pericarditis. (See "Acute pericarditis: Treatment and prognosis", section on 'Medical therapies'.)

The variable presentation and course of post-cardiac injury syndrome requires significant individualization of the approach to follow-up. We suggest the following approach for a typical patient with post-cardiac injury syndrome:

●Early follow-up – Following four weeks of therapy, early follow-up includes laboratory testing for inflammatory markers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]). Markers of inflammation that were elevated at the time of diagnosis should be trending toward more normal values following four weeks of therapy.

•Markers of inflammation that were elevated at the time of diagnosis should be trending toward more normal values following four weeks of therapy. If symptoms persist or inflammatory markers remain elevated at four weeks, close office-based follow-up with repeat laboratory testing for inflammatory markers (CRP and ESR) every two to four weeks until asymptomatic with improving markers of inflammation.

•If symptoms are resolved and inflammatory markers have normalized (or trend toward normal), office follow-up with laboratory testing for inflammatory markers (CRP and ESR) and echocardiography is performed at three months postdiagnosis.

●Long-term follow-up - Annual office follow-up is performed for several years, with repeat echocardiography if any signs or symptoms of constrictive pericarditis appear. (See "Constrictive pericarditis: Diagnostic evaluation".)

Management of refractory cases — Following initial treatment of post-cardiac injury syndrome with an NSAID and colchicine, a minority of patients have refractory symptoms. Other causes of pericarditis (eg, infection) are first excluded.

Glucocorticoid therapy — Refractory post-cardiac injury syndrome is treated like other types of refractory pericarditis with a course of glucocorticoids plus colchicine as second-line therapy (table 1). This involves moderate initial doses of glucocorticoid (eg, 0.25 to 0.50 mg/kg/day of prednisone for four weeks) followed by a slow taper (eg, over two to three months) plus colchicine (eg, 0.5 to 0.6 mg for six months or more) (table 1). There are conflicting data, mostly derived from observational studies, regarding optimal dosing and tapering of glucocorticoid therapy when used to treat pericarditis. Our approach to glucocorticoid therapy (which may be combined with NSAID therapy as a third-line therapy) in patients with pericarditis is discussed in more detail separately. (See "Acute pericarditis: Treatment and prognosis", section on 'Glucocorticoid dosing' and "Recurrent pericarditis", section on 'Glucocorticoids'.)

Among patients with recurrent or persistent autoreactive pericarditis with effusion (not limited to post-cardiac injury syndrome), pericardiocentesis with intrapericardial instillation of triamcinolone (300 mg/m²) has been proposed as an alternative to systemic therapy to avoid systemic side effects [43]. As these data are limited, this approach requires further investigation prior to widespread use. (See "Recurrent pericarditis", section on 'Intrapericardial glucocorticoid'.)

Other agents — The role of interleukin 1 inhibitor (rilonacept or anakinra) for patients with recurrent pericarditis and an inflammatory phenotype is discussed separately. (See "Recurrent pericarditis", section on 'Our approach' and "Recurrent pericarditis", section on 'Interleukin 1 inhibitors'.)

Treatment options for recurrent pericarditis with a noninflammatory phenotype are discussed separately. (See "Recurrent pericarditis", section on 'Our approach' and "Recurrent pericarditis", section on 'Other immune therapy'.)

PROGNOSIS — 

Although the prognosis of the post-cardiac injury syndrome is relatively good for most patients, a recurrence rate of between 10 and 15 percent has been reported [2]. In addition, because of a small but distinct risk of developing constrictive pericarditis, longer-term follow-up for several years appears to be warranted [2]. (See "Constrictive pericarditis: Clinical features and causes" and "Constrictive pericarditis: Diagnostic evaluation" and 'Follow-up' above.)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Non-ST-elevation acute coronary syndromes (non-ST-elevation myocardial infarction)" and "Society guideline links: ST-elevation myocardial infarction (STEMI)" and "Society guideline links: Pericardial disease".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Pericarditis in adults (The Basics)")

●Beyond the Basics topic (see "Patient education: Pericarditis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition – Post-cardiac injury syndromes are conditions in which inflammatory pericardial disease occurs after pericardial and/or myocardial injury, with a latent period (ranging from days to months) between the injury and the development of pericarditis. (See 'Definition' above.)

●Causes – The causes of post-cardiac injury syndrome include myocardial infarction (MI), pericardiotomy, trauma, and iatrogenic injury associated with percutaneous cardiac interventions. (See 'Causes and their frequencies' above.)

●Clinical features – Patients who develop post-cardiac injury syndrome present with symptoms and signs similar to those seen in patients with acute pericarditis in other clinical settings, such as pleuritic chest pain, pericardial friction rub (movie 1), fever, and leukocytosis. Cardiac tamponade is rare in this setting. (See 'Clinical features' above.)

●Evaluation – The diagnostic evaluation of all patients with suspected post-cardiac injury syndrome includes laboratory testing, a 12-lead ECG, a chest radiograph, and an echocardiogram. (See 'Evaluation' above.)

●Diagnosis – In the setting of one of the causes of post-cardiac injury syndrome (see 'Causes and their frequencies' above) and a latent period (ranging from days to months after the pericardial or myocardial injury), the combination of a pericardial friction rub and ECG findings typical for pericarditis strongly supports the diagnosis. The diagnosis is also strongly supported if an echocardiogram reveals a pericardial effusion at a time when effusions are no longer routine (nontrivial effusions are uncommon after 7 to 10 days postinjury), but a pericardial effusion is not always present. (See 'Diagnosis' above.)

●Prevention

•For cardiac surgery – For most patients undergoing cardiac surgery, we suggest postoperative prophylactic treatment with colchicine rather than expectant management (Grade 2B). Colchicine is the only therapy that has been demonstrated to reduce post-cardiac injury syndrome following cardiac surgery. However, there are concerns about adverse effects, mainly diarrhea and other gastrointestinal complaints, that have limited adoption of colchicine in this setting. Side effects appear to be lower when colchicine is started postoperatively rather than preoperatively. We begin colchicine one to three days following surgery (0.5 mg twice daily for patients ≥70 kg, 0.5 mg daily for those <70 kg) and continue therapy for a 30-day course. (See 'Colchicine' above.)

•For atrial fibrillation ablation – For patients undergoing atrial fibrillation (AF) ablation, we suggest not administering prophylactic treatment with colchicine (Grade 2C). (See 'Not established for AF ablation' above.)

●Treatment – For patients with post-cardiac injury syndrome, treatment is the same as for other types of acute pericarditis (table 1). (See 'Treatment' above and "Acute pericarditis: Treatment and prognosis".)

First-line treatment consists of the combination of nonsteroidal antiinflammatory drug (NSAID) plus colchicine. Either aspirin or a different NSAID (eg, ibuprofen, naproxen, etc) may be tried as initial therapy if there are no contraindications.

Most patients with pericarditis following acute MI are treated with aspirin for secondary prevention purposes. For patients with post cardiac injury syndrome post MI, the aspirin dose is increased to an antiinflammatory dose (table 1).

●Prognosis – The prognosis of the post-cardiac injury syndrome is relatively good for most patients, although 10 to 15 percent of patients will experience a recurrence. Patients require close office-based follow-up until they are asymptomatic with normalized inflammatory markers. (See 'Prognosis' above.)