Pericarditis, Constrictive

Introduction
Background

The thousand mysteries around us would not trouble but interest us, if only we had cheerful, healthy hearts.

–Nietzche

If we all had healthy hearts, the mysteries of the heart would not trouble us; however, constrictive pericarditis certainly has been a mystery and remains a diagnostic challenge to this day.

The history of constrictive pericarditis is replete with some of the most famous names in medicine. Richard Lower described a patient with dyspnea and an intermittent pulse in 1669. Lancisi first reported on the constrictive syndrome in 1828. Corrigan described the pericardial knock in 1842. Kussmaul described his sign and the associated paradoxical pulse in 1873.1,2,3

Constrictive pericarditis has symptoms that overlap a variety of diseases as diverse as myocardial infarction, aortic dissection, pneumonia, influenza, and connective tissue disorders. This overlap can confuse the most skilled diagnostician. An increased suspicion for constriction helps move it to the top of the broad differential diagnosis and provides for a correct diagnosis and timely therapy.

Constrictive pericarditis occurs when a thickened fibrotic pericardium, of whatever cause, impedes normal diastolic filling. This usually involves the parietal pericardium, although it can involve the visceral pericardium (see Pericarditis, Constrictive-Effusive). Acute and subacute forms of pericarditis (which may or may not be symptomatic) may deposit fibrin, which may, in turn, evoke a pericardial effusion. This often leads to pericardial organization, chronic fibrotic scarring, calcification, and restricted cardiac filling.4

The classic diagnostic conundrum of constrictive pericarditis is the difficulty in distinguishing it from restrictive cardiomyopathy (see Cardiomyopathy, Restrictive) and other syndromes associated with elevated right-sided pressures that all share similar symptoms, physical findings, and hemodynamics. Although obtaining a careful history and performing a physical examination remain the cornerstones of evaluation, technologic advances have facilitated diagnosis, particularly with the appropriate use of Doppler echocardiography, high-resolution computed tomography (CT), magnetic resonance imaging (MRI), and invasive hemodynamic measurement.
Pathophysiology

The normal pericardium is composed of 2 layers: the tough fibrous parietal pericardium and the smooth visceral pericardium. Usually, approximately 50 mL of fluid (plasma ultrafiltrate) is present in the intrapericardial space to minimize friction during cardiac motion.5

Acute and subacute forms of pericarditis (which may or may not be symptomatic) may deposit fibrin, which may, in turn, evoke a pericardial effusion. This often leads to pericardial organization, chronic fibrotic scarring, and calcification, most often involving the parietal pericardium (see Pericarditis, Constrictive-Effusive).6

This thickened fibrotic pericardium, regardless of cause, impedes normal late diastolic filling, distinguishing constrictive from restrictive pericarditis. Since the myocardium is unaffected, early ventricular filling during the first third of diastole is unimpeded, but afterwards, the stiff pericardium affects flow and hemodynamics. In other words, the ventricular pressure decreases rapidly early (producing a steep y descent on right atrial pressure waveform tracings) and then increases abruptly to a level that is sustained until systole ("dip-and-plateau waveform" or "square root sign" seen on right or left ventricular pressure waveform tracings).7

The clinical symptoms and classic hemodynamic findings can be explained by early rapid diastolic filling and elevation and equalization of the diastolic pressures in all of the cardiac chambers restricting late diastolic filling, leading to venous engorgement and decreased cardiac output, all secondary to a confining pericardium.

Frequency
United States

Similar to many diseases that in the past were predominantly infectious in origin, the clinical spectrum of constrictive pericarditis has changed in recent years. Approximately 9% of patients with acute pericarditis for any reason go on to develop constrictive physiology.8 T he true frequency is therefore dependent on the incidence of the specific causes of pericarditis, but since acute pericarditis is only clinically diagnosed in 1 in 1,000 hospital admissions, the frequency of a diagnosis of constrictive pericarditis is less than 1 in 10,000 hospital admissions.

International

In the developing world, infectious etiologies remain more prominent (tuberculosis has the highest total incidence).
Mortality/Morbidity

* Scant data exist because the disease is rare.
* The underlying disease usually determines the prognosis. Poorer prognoses are associated with malignancy and New York Heart Association (NYHA) class III or IV heart failure symptoms.
* Long-term survival after pericardiectomy depends on the underlying cause. Of common causes, idiopathic constrictive pericarditis has the best prognosis (88% survival at 7 years), followed by constriction due to cardiac surgery (66% at 7 years). The worst postpericardiectomy prognosis occurs in postradiation constrictive pericarditis (27% survival at 7 years). This likely represents confounding comorbidities. Predictors of poor outcomes in patients who undergo pericardiectomy including history of prior radiation, worsening renal function, pulmonary hypertension, systolic heart failure, hyponatremia, and advanced age.9

Race

* No race predilection exists for this disorder.

Sex

* Most likely a male predominance exists, with a male-to-female ratio of 3:1 in some studies.

Age

* Cases have been reported in persons aged 8-70 years. Predilection is likely reflective of the underlying disease.
* Historical studies suggest a median age of 45 years, while more recent studies suggest a median age of 61 years. This likely reflects a demographic change that is likely to continue.

Clinical
History

* Constrictive pericarditis presents with a myriad of symptoms, making a diagnosis based solely on clinical history virtually impossible. Additionally, these symptoms may develop slowly over a number of years such that patients may not be aware of all of their symptoms until questioned.
* Dyspnea tends to be the most common presenting symptom and occurs in virtually all patients. Fatigue and orthopnea are common.
* Lower-extremity edema and abdominal swelling and discomfort are other common symptoms. Nausea, vomiting, and right upper quadrant pain, if present, are thought to be due to hepatic congestion, bowel congestion, or both.
* The initial history may be more compatible with liver disease (cryptogenic cirrhosis) than with pericardial constriction because of the predominance of findings related to the venous system.
* Chest pain, presumably due to active inflammation, may be present, although this is observed in a minority of patients.

Physical

* General findings
o In the early stages, physical findings may be subtle, requiring close examination to avoid missing the diagnosis.
o In more advanced stages, the patient may appear ill, with marked muscle wasting, cachexia, or jaundice.
o Constriction should be considered in the presence of otherwise unexplained jugular venous distention, pleural effusion, hepatomegaly, or ascites.
* Cardiovascular findings
o Elevated jugular venous pressures are an almost universal finding.
o Avoid examining the patient only in the supine position because venous pressures may be above the angle of the jaw and inadvertently mistaken for normal.
o Sinus tachycardia is common while the blood pressure is normal or low, depending on the stage of the disease process.
o The apical impulse is often impalpable, and the patient may have distant or muffled heart sounds.
o A pericardial knock, which corresponds with the sudden cessation of ventricular filling early in diastole, occurs in approximately half the cases and may be mistaken for an S3 gallop. However, a knock is of higher frequency than an S3 and occurs slightly earlier in diastole.
o A cardiac murmur is typically not present unless concomitant valvular heart disease or a fibrous band that constricts the right ventricular outflow tract is present.
o Pulsus paradoxicum (paradoxus) is a variable finding and, if present, rarely exceeds 10 mm Hg unless a concomitant pericardial effusion with an abnormally elevated pressure exists.
o The Kussmaul sign (ie, elevation of systemic venous pressures with inspiration) is a common nonspecific finding, but this sign is also observed in patients with right ventricular failure, restrictive cardiomyopathy, right ventricular infarction, and tricuspid stenosis, although, importantly, not in patients with cardiac tamponade.
* Gastrointestinal, pulmonary, and other organ system findings
o Hepatomegaly with prominent hepatic pulsations can be detected in as many as 70% of patients.
o Other signs that result from chronic hepatic congestion include ascites, spider angiomata, and palmar erythema, which can contribute to the common but erroneous diagnosis of primary liver disease.
o Peripheral edema is a common finding, although it may be less prominent in younger patients with competent venous valves.

Causes

The varied etiologies of constrictive pericarditis parallel those of acute pericarditis (see Pericarditis, Acute), which is a common precipitant. All forms of pericarditis may eventually lead to pericardial constriction. Generally, these can be broken down by frequency into common, less common, and rare forms. The top 3 causes of constrictive pericarditis are idiopathic (presumably viral), postcardiothoracic surgery, and irradiation therapy, which, according to a recent study, are responsible for 46%, 37%, and 9%, respectively, of cases of constrictive pericarditis (in patients who underwent surgical therapy).9

* The following are common etiologies:
o Idiopathic: In many cases, particularly in developed countries, no antecedent diagnosis can be found. These cases are termed idiopathic. Reports by many authors indicate that a high percentage of idiopathic cases of constrictive pericarditis may be related to previously recognized or unrecognized viral pericarditis. Of the viruses, coxsackievirus A and B, other echoviruses, and adenoviruses are most commonly implicated.8
o Infectious (bacterial): Tuberculosis is the leading cause of constrictive pericarditis in developing nations but represents only a minority of causes in the United States and other developed countries. Bacterial infections that lead to purulent pericarditis are also declining in frequency. In the past, purulent pericarditis associated with pneumococcal pneumonia was the most common presentation of a bacterial source. However, the widespread use of antibiotics has drastically changed the frequency and spectrum of purulent pericarditis such that the most common presentation now occurs following cardiac surgery. An increasing number of gram-positive organisms, including multiple resistant strains of staphylococci, may be isolated. Group A and B streptococci and gram-negative rods (eg, Pseudomonas species, Escherichia coli, and Klebsiella species) have also been documented.
o Infectious (viral [see also Idiopathic]): Coxsackievirus, hepatitis, adenovirus, and echovirus.
o Radiation-induced: The long-term effects of thoracic and mediastinal radiation therapy (eg, used in the treatment of hematological, breast, and other malignancies) are being increasingly realized. The common features of radiation-induced cardiac complications stem from microcirculation injury with endothelial damage, capillary rupture, and platelet adhesion. This sets up an inflammatory response, which may either resolve or organize to form adhesions between the visceral pericardium and the parietal pericardium, which leads to constriction. Generally, radiation-induced constrictive pericarditis presents 5-10 years after radiation therapy and is more likely to present with an associated pericardial effusion. In a study by Bertog in 2004, the median time between radiation and pericardiectomy was 11 years, with a broad range of 2-30 years, which is consistent with other previous studies.9
o Postsurgical: Any operative or invasive (catheterization) procedure in which the pericardium is opened, manipulated, or damaged may invoke an inflammatory response, leading to constrictive pericarditis. The most common example is constrictive pericarditis in the setting of previous coronary artery bypass grafting.
* The following are less common etiologies:
o Infectious (fungal): Fungal infections are an uncommon source of constrictive pericarditis in patients who are immunocompetent. Nocardia species can be causative organisms, especially in endemic areas such as the Ohio Valley. Aspergillus, Candida, and Coccidioides species are important pathogens in patients infected with HIV and in other immunocompromised hosts.
o Neoplasms: Malignant involvement may also manifest as pericardial effusion (with or without tamponade) or as an encased heart with thickening of both visceral and parietal layers, resulting in constrictive physiology. Although many types of neoplasms have been reported, breast and lung carcinomas and lymphomas are the most common metastatic malignancies associated with constrictive pericarditis. Other malignancies that involve the pericardium with relative frequency include melanoma and mesothelioma.
o Uremia: Constrictive pericarditis may develop in association with long-term hemodialysis.
o Connective tissue disorders: Autoimmune disorders that involve the pericardium are not unusual, typically manifesting as a small pericardial effusion or as an episode of acute pericarditis. Chronic pericardial involvement is less common but can occur in patients with rheumatoid arthritis, usually associated with the presence of subcutaneous nodules. Systemic lupus erythematosus and scleroderma also may lead to constrictive pericarditis, and, in the latter, this carries a poor prognosis.
o Drug-induced: Procainamide and hydralazine have been reported to cause constrictive pericarditis through a drug-induced lupuslike syndrome. Methysergide therapy also has been implicated as a cause of constrictive pericarditis.
o Trauma: Although uncommon, both blunt and penetrating trauma to the chest wall have been reported to cause constrictive pericarditis, presumably through an inflammatory mechanism.
o Myocardial infarction: Postmyocardial infarction constrictive pericarditis has been reported. The patient typically has a history of Dressler syndrome or hemopericardium after thrombolytic therapy.
* The following are rare etiologies:
o Toxic or metabolic: Uremia with chronic hemodialysis can lead to constrictive pericarditis and is usually associated with a pericardial effusion.
o Intrapericardial instrumentation: Constrictive pericarditis after implantation of an epicardial pacemaker or automated implantable cardiac defibrillator is a rare but reported phenomenon.
o Hereditary: Mulibrey nanism is an autosomal recessive disorder characterized by multiple abnormalities, including dwarfism, constrictive pericarditis, abnormal fundi, and fibrous dysplasia of the long bones.
o Chemical trauma: Constrictive pericarditis following sclerotherapy for esophageal varices is rare.
o Chylopericardium: This is a rare cause of constrictive pericarditis.

http://emedicine.medscape.com/article/157096-overview