Critical Care of Pericardial Disease



Critical Care of Pericardial Disease


Akshay S. Desai

Kenneth L. Baughman


Deceased



Pericardial Anatomy

The pericardium consists of two layers: the inner layer (visceral pericardium) is a thin, elastic monolayer of mesothelial cells that is tightly adherent to the epicardial surface of the heart, whereas the outer layer (parietal pericardium) is a largely acellular network of collagen and elastin fibers that make up a thick, stiff fibrous envelope. The visceral pericardium reflects back near the origins of the great vessels and the junctions of the caval vessels with the right atrium, becoming continuous with the parietal pericardium and generating a potential space (pericardial sac) that is normally lubricated by up to 50 mL of serous fluid. Most of the heart (excepting a portion of the left atrium) and portions of the aorta, pulmonary trunk, pulmonary veins, and venae cavae are contained within this sac, which has ligamentous attachments to the diaphragm, sternum, and other structures in the anterior mediastinum. The main arterial blood supply of the pericardium is provided by the pericardiophrenic artery, a branch of the internal thoracic artery, whereas venous drainage occurs via pericardiophrenic veins that are tributaries of the brachiocephalic veins. Sensory enervation is provided by the phrenic nerves with vasomotor innervation from the sympathetic trunks [1,2].


Normal Physiology of the Pericardium

Although an intact pericardium is not critical to the maintenance of cardiovascular function, the pericardium does have several physiologically relevant functions. First, it provides important structural support for the heart, limiting excessive cardiac motion within the thoracic cavity during respiration and changes in body position. In addition, it acts as a lubricant (minimizing friction between the cardiac chambers and the surrounding structures) and as an anatomic barrier to infection. Perhaps the best-characterized mechanical function of the normal pericardium, however, is as a restraint on cardiac filling and rapid chamber dilation [3]. At low applied stresses, approximating those at physiologic cardiac volumes, pericardial tissue is quite compliant. As the distending pressure increases, however, it abruptly becomes quite stiff and resistant to further stress. As a result, the pericardium passively restrains intracardiac volume and limits ventricular filling, with a component of intracavitary filling pressure reflecting transmitted pericardial pressure. In addition, this pericardial restraint defines a total compliance for the system, enhancing ventricular interdependence by accentuating the consequences of septum-mediated ventricular interactions during diastolic filling [4].

The pericardium itself has a small capacitance reserve (150 to 250 mL) that admits initial increments in intrapericardial volume with trivial increases in intrapericardial pressures. Once this capacitance is exceeded, rapid increases in intrapericardial volume result in steep increments in intrapericardial pressures, with potentially deleterious consequences for cardiac filling and ventricular performance [5,6]. By contrast, gradual changes in myocardial or pericardial volume (well in excess of the normal pericardial reserve) may be accommodated without invoking dramatic consequences of pericardial restraint. In experimental models of chronic volume overload, the pericardium exhibits the ability to undergo gradual stretch and hypertrophy, enhancing its compliance and diminishing its impact on the ventricular pressure–volume relationship [7]. Such chronic stretch is the primary mechanism permitting the accommodation of chronic cardiac dilation (as in dilated cardiomyopathy) or large, slowly accumulating pericardial effusions (as in malignant lymphoma), without hemodynamic embarrassment (Fig. 35.1).


Pericardial Pathophysiology

Pericardial manifestations are seen in a wide spectrum of medical and surgical conditions, including a host of infectious, immune/inflammatory, and neoplastic disorders (Table 35.1). Broadly speaking, from the vantage point of critical care, there are three conditions to be considered: (i) acute pericarditis, (ii) pericardial effusion and tamponade, and (iii) constrictive pericarditis. We consider the diagnosis, pathophysiology, and management of each of these in turn in the discussion to follow.


Acute Pericarditis

Pericardial inflammation presents in many clinical settings and has a wide range of causes. Although pericarditis is classically identified by the clinical triad of acute chest pain, pericardial friction rub, and characteristic electrocardiographic changes, subacute and chronic presentations are also possible. It may occur as an isolated entity or as the result of systemic disease; though most often a strictly inflammatory fibrinous lesion without clinically recognizable fluid, sequelae including pericardial effusion (occasionally progressing to tamponade), pericardial constriction, or recurrent (relapsing) pericarditis are often seen. A prevalence of around 1% in autopsy studies suggests that pericarditis may frequently be subclinical [8]. Pericarditis is thought to account for around 5% of presentations to emergency departments for nonischemic chest pain [9].


Causes

Despite an ever-expanding array of diagnostic techniques, the vast majority of cases of pericarditis remain idiopathic in etiology [10,11,12]. Even when pericardial fluid or tissue samples are obtained, the cause is undefined in up to 30% of patients.
Broadly speaking, pericarditis is either infectious (two-thirds of cases) or noninfectious (one-third of cases) in etiology, with noninfectious cases attributable to one of a number of immune, neoplastic, traumatic, and metabolic conditions (see Table 35.1). A wide range of organisms cause infectious pericarditis, but viral infection remains the most common probable or identifiable cause. Organisms responsible for myocarditis are commonly implicated, particularly enteroviruses, adenoviruses, and influenza; herpes simplex and cytomegalovirus may also be important in immunocompromised individuals. Myopericarditis has also been reported after smallpox vaccination in US military personnel not previously exposed to vaccinia [13]. Although pericardial abnormalities are seen in up to 20% of patients with human immunodeficiency virus (HIV) infection, symptomatic pericarditis in these patients is commonly due to secondary infection (e.g., mycobacterial) or neoplasia (particularly lymphoma or Kaposi’s sarcoma), and the frequency decreases with effective antiretroviral therapy [14]. Bacterial pathogens typically cause purulent pericarditis, but are implicated infrequently in pericardial disease, typically as a consequence of hematogenous seeding or direct extension from adjacent infected tissues (lungs or pleural space) [15]. Mycobacterium tuberculosis causes up to 4% of acute pericarditis cases and 7% of tamponade presentations in developed countries, and remains an important causal factor in developing nations and immunocompromised hosts [16,17]. Tuberculosis-related pericarditis can require pericardial biopsy for diagnosis and is complicated by pericardial effusion or constriction in up to 50% of cases [18].






Figure 35.1. Pericardial pressure–volume relationship and relationship to development of pericardial tamponade. The ability of the pericardium to accommodate pericardial fluid without hemodynamic embarrassment depends heavily on the rate of fluid accumulation. Note the steepness of the relationship in normal pericardium and the marked flattening and shift to the right with chronic volume overload. [Adapted from Freeman G, LeWinter MM: Pericardial adaptations during chronic cardiac dilation in dogs. Circ Res 54:294–300, 1984.]

In the remainder of patients, pericarditis occurs in conjunction with a dissecting aortic aneurysm (in which blood leaks into the pericardial space), after blunt or sharp trauma to the chest, as a result of neoplastic invasion of the pericardium, after chest irradiation, in association with uremia or dialysis, after cardiac or other thoracic surgery, in association with an inflammatory or autoimmune disorder, or as a result of certain pharmacologic agents. Iatrogenic cases are increasingly common, with postpericardiotomy syndrome reported in up to 20% of patients at a median of 4 weeks following cardiac surgery [19] and symptomatic pericarditis in up to 2% of patients undergoing percutaneous coronary intervention, catheter ablation procedures, or implantation of active fixation pacemaker or defibrillator leads [10]. Pericarditis associated with acute transmural myocardial infarction and the delayed immune-mediated postinfarction pericarditis of Dressler’s syndrome used to be common, but the incidence has declined with the broader utilization of early reperfusion strategies for acute coronary syndromes (thrombolysis and primary angioplasty).


Presentation and Diagnosis

Although patients with acute pericarditis may be asymptomatic, the typical presentation is with chest pain that is retrosternal in location, sudden in onset, and exacerbated by inspiration (pleuritic). The pain may be made worse by lying supine and improved by sitting upright and leaning forward. Precordial distress may closely mimic angina, including a predominant pressure sensation with radiation to the neck, arms, or left shoulder. However, radiation of chest pain to one or both trapezius muscle ridges favors the diagnosis of pericarditis because the phrenic nerve, which innervates these muscles, traverses the pericardium. A prodrome of low-grade fever, malaise, and myalgia is common, but fever may be absent in elderly patients. Associated symptoms can include dyspnea, cough, anorexia, anxiety, and occasionally, odynophagia or hiccups.

Nearly 85% of patients with pericarditis have an audible friction rub during the course of their disease [12]. Typically, the rub is a high-pitched scratchy or squeaky sound best heard at the lower left sternal border or apex at end expiration with the patient leaning forward. Classically, it consists of three components corresponding to ventricular systole, early diastolic filling, and atrial contraction, and has been likened to the sound made when walking on crunchy snow. It is distinct from a pleural rub in that it is present throughout the respiratory cycle, whereas the pleural rub disappears when respirations are suspended. The pericardial friction rub is often a dynamic sound that can disappear and reappear over short periods of time. Because of this variable quality, frequent auscultation in the upright, supine, and left lateral decubitus positions is important for patients in whom a diagnosis of pericarditis is suspected.


Electrocardiogram

The electrocardiogram (ECG) is a key diagnostic test in suspected pericarditis, though typical changes are not always seen. The classic finding is widespread, concave ST-segment elevation, often with associated PR-segment depression (Fig. 35.2). Although the changes may appear regional and therefore mimic myocardial ischemia, reciprocal ST-segment depressions are absent, as are pathologic Q-waves. In addition, the ECG in pericarditis exhibits a typical pattern of evolution that is
distinct from that of patients with evolving myocardial infarction. In patients with pericarditis, the ECG on presentation usually demonstrates diffuse ST-segment elevation and PR-segment depression (stage I) and evolves through three subsequent phases [20]. During the evolutionary phase (stage II), all ST-junctions return to baseline more or less “in phase,” with little change in T-waves. (By contrast, in patients with ST-segment elevation due to acute myocardial injury, T-wave inversion begins to occur before the ST-segments return to baseline.) The T-waves subsequently flatten and invert (stage III) in all or most of the leads that showed ST-segment elevations. In stage IV, the T-waves return to their prepericarditic condition. The widespread T-wave inversions that appear in stage III are indistinguishable from those of diffuse myocardial injury, myocarditis, or biventricular injury. The entire ECG evolution occurs in a matter of days or weeks, but may not be seen in every patient. Often, the transition from stage III to stage IV is relatively slow, with some patients left with some degree of T-wave inversion for an indefinite period.








Table 35.1 Etiologies of Acute Pericardial Disease






















































Etiology Examples Incidence Treatment
Idiopathica 85%–90% Aspirin, NSAIDs
Infectious
   Virala
   Bacteriala
   Mycobacteriala
   Fungal
Echovirus, coxsackievirus, adenovirus, cytomegalovirus, hepatitis B, Epstein–Barr virus (infectious mononucleosis), HIV/AIDS Pneumococcus, Staphylococcus, Streptococcus, Mycoplasma, Borrelia spp. (Lyme disease), Haemophilus influenzae, Neisseria meningitidis, Mycobacterium tuberculosis, M. aviumintracellulare, Histoplasma, Coccidioides 1%–2%
1%–2%
4%–5%
Rare (< 1%)
Aspirin, NSAIDs
Antibiotics, surgical drainage
Antimycobacterial therapy and prednisone
Antifungal therapy, drainage
Immune/inflammatory Connective tissue diseasea (systemic lupus erythematosus, rheumatoid arthritis, scleroderma)
Arteritis (polyarteritis nodosa, temporal arteritis)
Drug induceda (e.g., procainamide, hydralazine, isoniazid, cyclosporine)
3%–5%
Rare (< 1%)
Aspirin, NSAIDs, glucocorticoids
Discontinue drug; aspirin, NSAIDs
Neoplastic Primary: mesothelioma, sarcoma, etc.
Secondarya: breast carcinoma, lung carcinoma, lymphoma
5%–7% NSAIDs, intrapericardial infusion of glucocorticoids
Myocardial infarction related
Aortic dissection related
Early postmyocardial infarction (MI)
Late postmyocardial infarction (Dressler’s syndrome)a
Proximal aortic dissection
5%–6% of patients with transmural MI
Formerly 3%–4% of patients with MI, much less in the era of early reperfusion
Rare (< 1%)
Aspirin (avoid NSAIDs)
Urgent surgery (do not drain)
Traumatica Blunt and penetrating trauma, postcardiopulmonary resuscitation NA NSAIDs (avoid aspirin)
Procedure and device related Early postcardiac surgery Post-ICD/pacemaker,a postangioplasty,a late post cardiotomy or thoracotomy (Dressler’s variant)a Common
Rare (< 1%)
Aspirin, NSAIDs
Aspirin, NSAIDs
Radiation induceda Chest wall irradiation Rare (< 1%) NSAIDs
Uremic or dialysis associated ∼5% of patients with chronic kidney disease predialysis, ∼ 13% after dialysis Initiate or intensify dialysis, NSAIDs
aConditions that manifest as acute pericarditis.

Although some 80% of patients with pericarditis exhibit a typical stage I ECG during their course [21], atypical variants (or even a normal ECG) may also be seen. An important ECG variant that can be quasidiagnostic is PR-segment (not PR-interval) depression in the absence of true ST-segment elevation, which though nonspecific, may be the only sign of pericarditis. This may occur as a consequence of superficial myocarditis affecting the atrium [22]. Although the ST-changes of pericarditis may occasionally resemble those of normal early
repolarization, a useful differentiating feature may be the ratio between the height of the ST-segment and the T-wave in lead V6. A ratio exceeding 0.24 favors the diagnosis of pericarditis [23].






Figure 35.2. Electrocardiogram (ECG) in acute pericarditis. Note the diffuse, upward concave ST-segment elevation and PR-segment depression (lead II).


Imaging and Additional Laboratory Testing

Although laboratory findings in patients with suspected pericarditis are nonspecific, measurement of serum markers of inflammation (leukocyte count, erythrocyte sedimentation rate, C-reactive protein, and lactate dehydrogenase) and myocardial necrosis (creatine kinase, and troponins) may help to establish or confirm the diagnosis, define the extent of associated myocardial injury, and guide subsequent follow-up. The 2004 European Society of Cardiology guidelines on the management of pericardial diseases [24] therefore advise measurement of these parameters as part of the initial diagnostic evaluation in all patients, but this recommendation remains somewhat controversial. A markedly elevated white blood cell count, particularly in association with high fever, should raise suspicion for purulent pericarditis, and may prompt sampling of pericardial fluid (if present) for diagnosis. Cardiac enzymes including creatine kinase (creatine kinase, total and MB-fraction) and troponins are commonly elevated in patients with pericarditis due to associated epicardial inflammation or myocarditis [25]. Elevations in troponin I are seen more commonly than those in CK-MB and are frequently associated with male gender, ST-segment elevation, younger age at presentation, and pericardial effusion. The degree of troponin elevation is roughly related to the extent of myocardial inflammation and, distinct from acute coronary syndromes, does not appear to correlate with long-term prognosis [26]. Routine measurement of cardiac troponins in patients with suspected or definite pericarditis may therefore be unnecessary, unless there is suspicion for associated transmural myocardial infarction by ECG (due to the presence of pathologic Q-waves) [27]. Similarly, routine serologic testing for antinuclear antibodies or rheumatoid factor is rarely helpful, save in those patients in whom other clinical features suggest underlying connective tissue illness.

The chest radiograph is typically normal in acute pericarditis, but is often performed as a matter of course to assess for abnormalities in the mediastinum or lung fields, which may suggest an etiology, and to exclude cardiomegaly, which suggests the presence of a substantial pericardial effusion (> 250 mL). Pericardial calcification is rarely seen, but may suggest constrictive pericarditis. Any suspicion for cardiomegaly should prompt a transthoracic echocardiogram to assess for hemodynamically significant pericardial effusion or tamponade. Routine echocardiography in patients with unequivocal evidence of pericarditis and normal hemodynamics by physical examination is probably unnecessary, though the detection of a pericardial effusion may help to support the diagnosis. In addition, detection of wall motion abnormalities or left ventricular dysfunction on echocardiography may be helpful in detecting associated myocardial infarction or in assessing the severity of associated myocarditis.


Natural History and Management

There are no large, randomized, controlled clinical trials to guide the therapy of patients with acute pericarditis. Initial management is directed at screening for specific etiologies and underlying conditions that may alter the treatment strategy (e.g., connective tissue disease, HIV infection, and tuberculosis) and control of symptoms. In the vast majority of patients, acute idiopathic pericarditis is a self-limited disease without significant complications or recurrence, and may be safely managed in the outpatient setting [28]. A subset of patients with high-risk features including fever greater than 38°C, subacute course (symptoms developing over days or weeks), large pericardial effusion (> 20 mm in width in diastole by echocardiography), cardiac tamponade, or failure to respond to treatment with aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) should be considered for hospital admission to permit additional observation and a more extensive etiologic work-up [29]. Immunosuppressed patients and those with blunt or penetrating chest trauma, serologic evidence of myocarditis (based on elevated cardiac biomarkers), or need for oral anticoagulant therapy may also be at risk for complications and warrant closer observation [30].

Treatment of pericarditis may vary on the basis of etiology. For the minority of cases in which a specific diagnosis is identified, therapy should be tailored appropriately, as outlined in
Table 35.1. (Details of treatment for specific conditions are beyond the scope of this discussion.) In uncomplicated cases of idiopathic pericarditis, treatment with NSAIDs is the cornerstone of therapy. Across the board, these agents are effective in reducing inflammation and symptoms of pain, fever, and malaise associated with pericarditis. Limited observational data suggest that the various available NSAIDs have comparable efficacy [31]. As a first-line agent, many favor treatment with ibuprofen, which is well tolerated and can easily be titrated over a range of doses. The typical dose is 600 mg every 6 hours, which sometimes relieves pain within 15 minutes to 2 hours of the first dose. Depending on patient tolerance and therapeutic response, the individual dose can be reduced to 400 mg or raised to 800 mg or greater with continued observation for side effects. Should this fail, aspirin 600 to 900 mg four times per day may be given. Indomethacin may be used, always given on a full stomach and in divided doses from 100 to 200 mg per day, beginning with 25 mg every 6 hours. In patients with myocardial infarction–related pericarditis, indomethacin should probably be avoided in light of experimental work showing that it reduces coronary flow, increases experimental infarction size, and raises blood pressure. Aspirin is the agent of choice in these cases because among the NSAIDs, it least retards scar formation in the infracted heart [32]. In all patients receiving high-dose NSAIDs, gastrointestinal protection with an antacid or proton–pump inhibitor should be considered to reduce the risk of drug-induced gastritis or bleeding.

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Sep 5, 2016 | Posted by in CRITICAL CARE | Comments Off on Critical Care of Pericardial Disease

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