Constrictive pericarditis in the twenty-first century: An old disease revisited

Abstract

Constrictive pericarditis (CP) has been recognized for centuries and is an uncommon cause of heart failure with preserved ejection fraction. In developing countries, tuberculosis is the primary cause of CP, whereas in developed countries, most cases are idiopathic. In CP, the pericardium becomes thickened, fibrotic, and sometimes calcified, effectively “choking” the heart by impairing diastolic relaxation while preserving systolic contraction. As a result, right-sided heart failure develops and progressively worsens. Clinical diagnosis is often delayed because the disease shares features with more common conditions, including other causes of heart failure and non-cardiac disorders such as chronic liver disease. The triad of elevated jugular venous pressure, a diastolic apical impulse, and a pericardial knock should raise suspicion for CP. Chest radiography typically demonstrates a normal-sized cardiac silhouette and, particularly in advanced cases, curvilinear “egg-shell” pericardial calcification. In recent decades, non-invasive multimodality imaging has largely replaced invasive cardiac catheterization as the gold standard for the diagnosis of CP. In clinical practice, transthoracic echocardiography is the preferred initial imaging modality. The Mayo Clinic echocardiographic criteria help differentiate CP from restrictive cardiomyopathy. Cardiac magnetic resonance provides high-resolution anatomical imaging together with advanced tissue characterization and dynamic hemodynamic assessment. Cardiac computed tomography is the preferred modality for detecting and characterizing pericardial calcification. For clinical management, CP can be classified into inflammatory and non-inflammatory phenotypes based on inflammatory marker levels (e.g., C-reactive protein), the presence of pericardial edema and late gadolinium enhancement on cardiac magnetic resonance imaging, and evidence of pericardial inflammation on 18F-fluoro-2-deoxy-2-D-glucose positron emission tomography. Since the beginning of the 21^st century, the management of CP has shifted from a “one-size-fits-all” approach toward a more personalized, evidence-based strategy. Anti-inflammatory therapy, including colchicine and corticosteroids as first-line agents and biologic therapies such as anakinra and rilonacept as second-line agents, may be beneficial for patients with inflammatory CP. For refractory cases, patients with the non-inflammatory phenotype, and those with extensive calcification, radical pericardiectomy remains the only potentially curative treatment. It is hoped that future advances in diagnostic modalities and personalized therapeutic strategies will further improve or replace current approaches.

Key Words: Constrictive pericarditis; Diastolic heart failure; Echocardiography; Magnetic resonance imaging; Colchicine; Pericardiectomy

Core Tip: constrictive pericarditis (CP) is characterized by pericardial thickening and fibrosis, resulting in impaired diastolic relaxation and progressive right-sided heart failure. Diagnosis is often delayed because of overlapping features with other causes of heart failure and chronic liver disease. Advances in noninvasive multimodality imaging, particularly transthoracic echocardiography, cardiac magnetic resonance, and cardiac computed tomography, have improved diagnostic accuracy. Management has evolved toward a phenotype-based approach, with anti-inflammatory therapy for inflammatory CP and radial pericardiectomy remaining the only potentially curative treatment for non-inflammatory, refractory, or calcified disease.

INTRODUCTION

Constrictive pericarditis (CP) is a well-recognized but relatively uncommon cause of diastolic dysfunction and heart failure with preserved ejection fraction. In this condition, chronic fibrous thickening of the pericardium, with or without calcification, impairs diastolic filling of the heart. Early diagnosis can be challenging because CP may mimic more common conditions, including chronic liver disease and systolic heart failure. Once diagnosed, surgery remains the only potentially curative treatment. Prompt treatment of acute pericarditis may prevent progression to CP. Over the past few decades, the diagnostic landscape of CP has changed considerably. With the advent of cardiac computed tomography (CT) scan and cardiac magnetic resonance (CMR), CP is increasingly being diagnosed at earlier stages. In a recently published retrospective cohort study from Australia, 763 (1.7%) of 45445 patients hospitalized with pericardial disease between 2004 to 2021 were diagnosed with CP[1].

Tuberculosis (TB) is no longer the leading cause of CP, particularly in developed countries. In recent decades, the management of CP has shifted from a “one-size-fits-all” approach toward a more personalized, evidence-based strategy. Recent guidelines from major professional societies recommend anti-inflammatory therapy for patients with inflammatory CP and pericardiectomy for those with irreversible non-inflammatory CP[2-4]. An up-to-date understanding of these advances is essential for the timely diagnosis and effective management of CP.

METHODOLOGY

For this narrative review, a literature search was conducted using PubMed, EMBASE, ScienceDirect and Google Scholar to identify articles published up to February 2026. To identify studies on CP, the following search terms were used: (1) “Pericarditis”; and (2) “Constrictive” or “constriction”. The search was then repeated using terms related to the common etiologies of CP, including: (1) “Idiopathic”; (2) “Tuberculous”; (3) “Post-surgery”; (4) “Autoimmune”; (5) “Malignant”; (6) “Radiation”; and (7) “Uraemic or uremic”. The retrieved articles were screened by title and content to identify relevant studies.

TYPES OF CONSTRICTION

Pericardial constriction can be classified into three types: (1) Transient constriction; (2) Effusive-CP (ECP); and (3) Chronic CP[2,3]. Pericardial constriction may occur with or without active inflammation. The term CP refers to pericardial constriction associated with pericardial inflammation.

Transient constriction is a reversible form of pericardial constriction caused by inflammatory pericardial edema. It typically resolves spontaneously or after 3-6 months of anti-inflammatory therapy.

ECP is characterized by the presence of a pericardial effusion and firm adhesion of the visceral pericardium to the cardiac surface. Hemodynamically, ECP is defined by a failure of the right atrial pressure to decrease by at least 50% or to fall below 10 mmHg after pericardiocentesis. ECP may also be diagnosed using non-invasive imaging modalities. Standard treatment consists of pericardiocentesis followed by medical therapy, with surgery reserved for persistent cases.

Chronic CP is defined as persistent pericardial constriction lasting beyond 3-6 months. Medical therapy has a limited role, and radical pericardiectomy is often the treatment of choice.

HISTORICAL BACKGROUND

Hippocrates recognized the existence of the pericardium. Pericardial diseases became identifiable following the introduction of postmortem examination. In 1669, Lower[5] described CP in a patient with dyspnea and an intermittent pulse. In 1842, Chevers[6] described the clinical features of CP, and Corrigan described the pericardial knock[7]. In 1896, Pick[8] reported a case of CP associated with ascites and hepatomegaly, leading to the introduction of the eponym “Pick’s disease”. The first successful pericardiectomy for CP was performed by the German surgeon Ludwig Rehn in 1913, with further refinements introduced by Shumacker[9] in the early 20^th century. Modern management of CP was pioneered in the United States by Sir Paul Dudley White[10], widely regarded as the father of American Cardiology.

PATHOPHYSIOLOGY

In CP, the pericardium becomes thickened, fibrotic and sometimes calcified, resulting in obliteration of the pericardial space. The rigid pericardium fixes the total cardiac volume and leads to ventricular interdependence, in which increased filling of one ventricle occurs at the expense of reduced filling of the other. As the disease progresses, diastolic pressures in all four cardiac chambers become equalized, and the normal relationship between intrathoracic and intracardiac pressures is lost[11]. When atrial pressures rise to ≥ 10 mmHg, peripheral venous congestion develops, leading to dependent edema, ascites, and congestive hepatomegaly. As atrial pressure increases further, patients develop dyspnea on exertion, orthopnea, and pleural effusions. In the advanced stages of disease, cardiac cachexia may develop[12].

CP may be result from infectious or non-infectious etiologies. Regardless of the initial trigger, the disease progresses through a cascade of inflammation, abnormal healing, fibrosis and calcification. The initial insult triggers an inflammatory response, leading to the release of proinflammatory cytokines, including interleukin-6 (IL-6), IL-8, interferon-γ, and tumor necrosis factor-α, which recruit and activate additional inflammatory cells[13-15]. Activated leukocytes subsequently release profibrotic cytokines, such as IL-13, connective tissue growth factor, and transforming growth factor-β, all of which promote extracellular matrix formation, collagen deposition and abnormal tissue repair. Ultimately, pericardial fibrosis, thickening and dystrophic calcification develop[13-16]. Transforming growth factor-β appears to be the principal regulator of extracellular matrix production and fibrosis[16]. Genetic factors and autoimmunity appear to play important roles, particularly in recurrent CP[13,17,18]. Mutations in genes involved in innate immunity may contribute to autoinflammatory syndromes and recurrent CP. Pathogenic variants in the MEV gene (associated with familial Mediterranean fever), Nod-like receptor protein 3 (NLRP3; associated with Cryopyrin-Associated Periodic Syndromes) and TNFRSF1A (associated with tumor necrosis factor receptor-associated periodic syndrome [TRAPS]) have been identified in patients with recurrent pericarditis.

Recurrent pericarditis is thought to be predominantly immune mediated[19,20]. Chronic autoantibody-mediated inflammation may lead to recurrent pericarditis and, ultimately, CP. This mechanism is particularly relevant in CP associated with autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Anti-nuclear antibodies are detected more frequently in patients with recurrent pericarditis than in healthy controls, with reported positivity rates of up to 43.3%. Immune complex deposition within pericardium may result in inflammation, fibrosis, and eventual constriction, as observed in conditions such as systemic sclerosis. Figure 1 presents a directed acyclic graph illustrating the proposed pathophysiological mechanisms of CP.

Figure 1 Directed acyclic graph approach to pathophysiology of constrictive pericarditis. CP: Constrictive pericarditis; TB: Tuberculosis.

Table 1 Sensitivity, specificity, positive predictive value and negative predictive value of echocardiographic parameters of Mayo Clinic Criteria for the diagnosis of constrictive pericarditis.

Echocardiographic parameter	Sensitivity	Specificity	PPV	NPV
Respirophasic ventricular septal motion	94%	73%	93%	77%
MV e’ medial > 8 cm/second	81%	91%	97%	58%
Annulus reversus	71%	79%	93%	45%
Diastolic hepatic vein expiratory reversal/forward flow velocity ≥ 0.8	73%	66%	86%	42%
Respirophasic ventricular septal motion + MV e’ medial > 8 cm/second	80%	96%	99%	58%
Respirophasic ventricular septal motion + MV e’ medial > 8 cm/second + diastolic hepatic vein expiratory reversal/forward flow velocity ≥ 0.8	67%	99%	100%	50%

PPV: Positive predictive value; NPV: Negative predictive value; MV: Mitral valve.

ETIOLOGY

CP may develop after any type of pericarditis. Historically, TB was the most common cause of CP[21,22]. However, TB is no longer the leading cause in developed countries. In these settings, the most commonly reported etiologies include: (1) Idiopathic or viral (42%-49%); (2) Post-cardiac surgery (11%-37%); (3) Post-radiation therapy, primarily for breast cancer or Hodgkin lymphoma (9%-31%); (4) Connective tissue disorders (3%-7%); (5) Post-infectious causes (purulent pericarditis or TB; 3%-6%); and (6) Miscellaneous causes (< 10%)[2]. In a registry-based study of 534 consecutive patients who underwent pericardiectomy for CP at the Cleveland Clinic (United States) between January 2000 and January 2022, 64% (n = 344) had idiopathic or viral CP, 25% (n = 130) had postcardiotomy CP, 6% (n = 31) had post-radiotherapy CP, and 5% (n = 27) had CP due to miscellaneous causes[23]. In developing countries, TB remains the leading cause of CP[24-26]. In a series of 124 patients who underwent pericardiectomy for CP in India, TB was the most common etiology, accounting for 64 cases (51.6%)[25,27]. In a more recent study from northeastearn India, postoperative biopsy confirmed TB as the underlying etiology in 28 of 42 patients (66.7%), whereas 14 patients (33.3%) had a nonspecific etiology[24]. Similarly, TB was identified as the cause for CP in 11 of 25 patients (44%) who underwent pericardiectomy in a Tunisian study[26].

Interestingly, in this era of human immunodeficiency virus (HIV) infection, an association between HIV and CP has been observed, particularly in Africa. In a systematic review and meta-analysis of 130 studies involving 11325 patients with CP, HIV infection was present in 29.1% of patients from Africa[27]. Temporal trends indicate that the age at diagnosis of CP has increased markedly since 1990, and patients from Africa and Asia are generally younger at diagnosis than those from Europe and the Americas[27].

The risk of progression from acute pericarditis to CP varies according to the underlying etiology. TB pericarditis carries the highest risk of progression: Transient constriction occurs in approximately 10% of patients, whereas chronic CP develops in 20%-50% despite appropriate anti-TB therapy[28]. In contrast, the risk of progression is < 1% in idiopathic or viral pericarditis, 2%-5% in immune-mediated and neoplastic pericardial disease, and 20%-30% in purulent pericarditis[13].

In CP, fibrocalcific changes may be confined to the pericardium, as in idiopathic CP, where the parietal pericardium is markedly thickened and rigid, whereas the visceral pericardium is only mildly inflamed. Post-radiation pericarditis is characterized primarily by firm adhesion of the visceral pericardium to the myocardium. In tuberculous CP, the pericardium becomes thickened and calcified, and in severe cases, dystrophic calcification may also involve the myocardium. At sites of active inflammation, the pericardium is thickened and highly vascularized, increasing the risk of intraoperative bleeding[29].

CLINICAL PRESENTATION

Early in the course of the disease, patients may present with symptoms related to reduced cardiac output rather than elevated filling pressures. These include fatigue and exertional dyspnea. Established CP is characterized clinically by features of severe right-sided heart failure. A history of prior pericarditis may be present. Common symptoms include dyspnea, fatigue, weight gain, and swelling of the legs and abdomen. Abdominal symptoms are typically caused by ascites or congestive hepatomegaly. Not uncommonly, patients undergo extensive evaluation for ascites or pleural effusions before being referred for cardiac assessment[30].

Typical signs include dependent edema and elevated jugular venous pressure (JVP) with a prominent y descent. Elevated JVP is present in approximately 93% of patients[31]. In some cases, the JVP is so markedly elevated that the upper limit of the venous column extends above the angle of the jaw when the patient is positioned at 45˚, becoming fully appreciable only in the standing position[30]. The apical impulse may be impalpable or palpable during diastole rather than systole[32]. A high-pitched early diastolic pericardial knock, best heard along the left sternal border, is present in nearly half of patients.

The triad of elevated JVP, a diastolic apical impulse (or precordial impulse), and a pericardial knock should raise suspicion for CP in clinical practice[32]. Kussmaul’s sign and pulsus paradoxus are present in approximately one-fifth of patients with CP[31]. Kussmaul’s sign is characterized by a paradoxical rise, or less commonly, failure of the JVP to fall during inspiration. It may also be observed in patients with tricuspid valve disease and right-sided heart failure. Pulsus paradoxus is defined as a decrease in systolic blood pressure of more than 10 mmHg during inspiration and is more commonly associated with cardiac tamponade. A pansystolic murmur of functional tricuspid regurgitation may also be audible[30].

A high degree of clinical suspicion is needed for the diagnosis of CP. Signs of congestive heart failure without apparent etiology should raise suspicion for CP.

INVESTIGATIONS

The purpose of the investigation is to confirm the diagnosis of CP, determine the underlying etiology, and formulate an appropriate management strategy.

Clinical evaluation, including a thorough history, is essential. In regions where TB is endemic, TB remains the leading cause of CP; therefore, a history of current or previous pulmonary or extrapulmonary TB may suggest tuberculous CP. A history of acute pericarditis, prior cardiac surgery, or chest irradiation may indicate the underlying etiology. Systemic symptoms, such as fever, weight loss, and night sweats, may suggest TB or malignancy. Autoimmune diseases, including RA, SLE, and other connective tissue disorders, may point to an autoimmune etiology. A history of HIV infection should also be considered.

Hemodynamically, constrictive pathophysiology is characterized by dissociation between intrathoracic and intracardiac pressures during respiration, resulting in accentuated ventricular interdependence and elevated diastolic filling pressures in right and left cardiac chambers[3]. Non-invasive multimodality imaging has largely replaced invasive hemodynamic testing for the routine diagnosis of CP. Among the available imaging modalities, echocardiography, particularly transthoracic echocardiography (TTE) is the preferred first-line investigation in clinical practice. Cardiac CT scan and CMR play complementary role. Cardiac catheterization remains valuable in diagnostically challenging cases. In the era of echocardiography, CT and CMR, CXR and ECG have a limited role. During the earlier 20^th century, CXR and ECG were the primary tools available for the evaluation of CP[33]. In his 1951 Circulation article “Chronic constrictive pericarditis” Paul Dudley White, widely regarded as the father of American Cardiology, identified CXR, ECG and cardiac catheterization as the principal diagnostic tools for CP[34].

Chest skiagram

CXR has a relatively low diagnostic yield in CP. The cardiac silhouette is typically normal in size. Pericardial calcification is present in approximately one quarter of patients[35,36]. When present, curvilinear calcification is better visualized on lateral or oblique views than on the anteroposterior view (Figure 2). Small areas of calcification may not be detected on chest radiography. The lung fields are typically clear.

Figure 2 Chest X-ray. A: Postero-anterior; B: Left lateral. Postero-anterior and left lateral views showing curvilinear calcification around the heart.

ECG

ECG has limited diagnostic value in CP, as there are no specific electrocardiographic findings. Typical abnormalities include low voltage QRS complexes and T-wave flattening or inversion (Figure 3). Advanced disease may be associated with atrial fibrillation and left atrial enlargement.

Figure 3 Electrocardiography. Inverted T waves in precordial and limb leads, and low QRS voltage in limb leads.

Echocardiography

TTE is often the first-line imaging modality in clinical practice. The overall diagnostic yield of echocardiography is approximately 84%[35]. Two-dimensional, M-mode and Doppler echocardiography provide complementary structural and functional information in patients with CP. The altered hemodynamics in CP result in leftward interventricular septum (IVS) shift during inspiration, a mitral inflow pattern with predominant E-wave velocity, elevated medial mitral annular e’ velocity on tissue Doppler imaging, a plethoric inferior vena cava (IVC), and expiratory late-diastolic flow reversal in the hepatic veins[3]. Two-dimensional and M-mode echocardiographic findings include normal-sized ventricles, dilated atria, exaggerated respirophasic IVS motion (septal bounce; Video 1), a thickened echogenic pericardium, and a dilated IVC with little or no respiratory variation. Doppler echocardiography demonstrates exaggerated respiratory variation in mitral and tricuspid inflow velocities and expiratory diastolic flow reversal in the hepatic veins. Tissue Doppler imaging demonstrates increased medial mitral annular e′ velocity and annulus reversus. Correspondingly, strain reversus may be observed on myocardial strain imaging.

In CP, exaggerated respirophasic movement of the IVS, or septal bounce, occurs as a result of ventricular interdependence. Septal bounce is less specific than exaggerated respirophasic IVS motion. IVC plethora may also be observed in RV failure and cardiac tamponade. Exaggerated respiratory variation in mitral and tricuspid inflow velocities results from dissociation between intrathoracic and intracardiac pressures but has limited specificity. Annulus reversus and strain reversus result from the tethering effect of pericardial adhesions on the lateral mitral annulus, with relative sparing of the medial mitral annulus. The medial mitral annular e′ velocity is typically measuring ≥ 9 cm/second. On hepatic vein Doppler, a ratio of diastolic reversal velocity to diastolic forward flow velocity ≥ 0.79 during expiration is considered diagnostic of CP[37,38]. The ratio of LV lateral wall longitudinal strain to LV septal wall longitudinal strain is typically < 0.96. Among echocardiographic findings, exaggerated respirophasic IVS motion is the most sensitive sign of CP, whereas expiratory diastolic hepatic vein flow reversal is the most specific. The Mayo Clinic Criteria are useful for differentiating CP from restrictive cardiomyopathy (RCM)[38]. Figure 4 illustrates the characteristic echocardiographic findings of CP. Table 1 summarizes the sensitivity, specificity, positive predictive value, and negative predictive value of the echocardiographic parameters included in the Mayo Clinic Criteria for the diagnosis of CP[3].

Figure 4 Transthoracic echocardiography. A: Thickened and calcified pericardium in left parasternal short-axis view; B and C: Respirophasic shift of interventricular septum in apical 4-chamber view; D: Mitral valve E/A 2.2 in pulsed wave Doppler echocardiography; E: Medial mitral annular velocity 10.4 cm/second in tissue Doppler imaging; F: Dilated, non-collapsing inferior vena cava in two-dimensional-guided M-mode echocardiography in subcostal view.

Cardiac CT scan

The most distinctive contribution of cardiac CT to the diagnosis of CP is the detection and characterization of pericardial calcification. In this regard, CT is superior to echocardiography and CMR[39,40]. Accordingly, cardiac CT is the imaging modality of choice for detecting pericardial calcification and calcific involvement of the adjacent myocardium[41]. The reported diagnostic yield of CT is as high as 93%[35]. On cardiac CT, a pericardial thickness of up to 2 mm is considered normal[42,43], whereas a thickness > 3-4 mm is considered abnormal[42,43]. Although CP can occur in the presence of a normal pericardial thickness, a completely normal CT examination makes the diagnosis unlikely[35]. Extensive pericardial calcification strongly suggests a chronic, non-inflammatory phenotype of CP that is unlikely to respond to anti-inflammatory therapy (Figure 5)[44,45].

Figure 5 Cardiac computed tomography scan. A and B: Thickened and calcified pericardium around the heart.

Cardiac CT also delineates thoracic anatomy before pericardiectomy, particularly the relationship between the cardiovascular structures and the sternum[3]. Compared with echocardiography and CMR, CT has limited ability to evaluate septal motion abnormalities[37]. However, when CMR is contraindicated, cine CT can be used to assess diastolic function and ventricular coupling. Contrast-enhanced CT can evaluate pericardial inflammation through delayed enhancement, while dual-energy CT and photon-counting CT provide advanced tissue characterization[39].

CMR

CMR combines high-resolution anatomical imaging with advanced tissue characterization and dynamic hemodynamic assessment. In clinical practice, CMR complements echocardiography and has become a cornerstone of the diagnostic evaluation of CP[39,46,47].

For comprehensive evaluation of CP, commonly used CMR sequences include bright blood gradient echo, black blood spin-echo, including short tau inversion recovery, and late gadolinium enhancement (LGE), which provide complementary T1- and T2-weighted information[44]. Supportive CMR findings include pericardial thickening, myopericardial tethering (including on radiofrequency tagging sequences), conical or tubular ventricular deformation, diastolic restraint, interventricular septal bounce, and a dilated IVC[44]. As with cardiac CT, a pericardial thickness up to 2 mm is considered normal on CMR[42,43]. CMR is comparable to cardiac CT for detecting pericardial thickening; however, it is less sensitive for detecting pericardial calcification. Black-blood spin echo sequences are particularly useful for detecting pericardial thickening, which most commonly involves the right ventricle and the anterior atrioventricular groove. Similar to echocardiography, respirophasic septal shift in real-time free-breathing cine short-axis imaging is a key feature of constrictive physiology[44].

Exaggerated respiratory variation in mitral (> 25%) and tricuspid (> 40%) inflow velocities on real-time phase-contrast imaging during 10 seconds of free breathing is another characteristic finding of CP[48]. Pericardial edema on T2-weighted short tau inversion recovery (STIR) imaging and LGE on phase-sensitive inversion recovery indicate concurrent or persistent pericardial inflammation[37,41], and may predict a favorable response to anti-inflammatory therapy[49].

Compared with echocardiography, the limitations of CMR include limited availability, higher cost, longer acquisition times, and contraindications in patients with non-MRI-compatible devices or severe claustrophobia[39]. A standard CMR examination for CP typically requires 30-60 minutes and depends on patient cooperation, including breath-holding[47-50]. Importantly, the absence of pericardial thickening does not exclude the diagnosis of CP. In a series of surgically confirmed cases of CP, 18% of patients had normal pericardial thickness[51]. Table 2 summarizes the diagnostic performance of multimodality imaging for CP.

Table 2 Comparative diagnostic performance of multimodality imaging in constrictive pericarditis.

Finding	Echocardiography	CT scan	CMR
Pericardial thickening	Useful, TEE better, less commonly used	Very useful, best for demonstrating calcification	Very useful
Pericardial calcification	Useful	Very useful	Less useful
Inflammation	Less useful, limited ability	Less useful, may be possible with late iodine enhancement	Less useful, best modality
Tissue characterization	Less useful, limited ability	Less useful, limited ability	Very useful, best modality
Respirophasic ventricular septal shift	Useful, commonly used	Less useful	Very useful
IVC dilatation	Very useful, commonly used	Very useful	Very useful
Physiology, MV medial e’, hepatic vein flow reversal	Very useful, commonly used	Less useful, limited ability	Very useful, less commonly used
Current indication	First-line imaging modality	Second-line, if echo is inconclusive	Second-line, if echo is inconclusive

CMR: Cardiac magnetic resonance; CT: Computed tomography; IVC: Inferior vena cava; MV: Mitral valve; TEE: Transesophageal echocardiography.

CARDIAC CATHETERIZATION

Cardiac catheterization has traditionally been considered the gold standard for the definitive diagnosis of CP, particularly when non-invasive imaging is inconclusive. It identifies the characteristic hemodynamic abnormalities caused by a rigid, noncompliant pericardium that restricts diastolic filling and enhances ventricular interdependence.

Procedural considerations for cardiac catheterization include: (1) Simultaneous biventricular pressure measurements to accurately assess ventricular discordance and interdependence[52]; (2) The use of adequately sized, multi-side-hole catheters (e.g., 6F pigtail or multipurpose)[52]; (3) A volume challenge when initial pressure measurements are not conclusive, such as in occult constriction, using rapid infusion of 500-1000 mL of normal saline over 6-8 minutes to unmask characteristic hemodynamic changes[53,54]; and (4) Temporary pacing in patients with atrial fibrillation to regularize the heart rate during the procedure, thereby preventing irregular rhythms from obscuring respiratory variations in hemodynamic measurements[54].

The key hemodynamic findings include: (1) Equalization of diastolic pressures: End-diastolic pressures in all four cardiac chambers - right atrial pressure, right ventricular (RV) end-diastolic pressure, left ventricular (LV) end-diastolic pressure, and pulmonary capillary wedge pressure - are typically elevated and equalized to within 5 mmHg of each other; (2) The “dip-and-plateau” or “square root” sign: Ventricular pressure tracings demonstrate a rapid decline in early diastole followed by an abrupt rise and plateau, reflecting the sudden limitation of ventricular filling by the rigid pericardium; and (3) A prominent y descent (“W” sign) on the right atrial pressure tracing: Right atrial pressure tracings show steep x and y descents, producing a characteristic “W” or “M” configuration.

However, most of these hemodynamic features are also observed in RCM. The hemodynamic findings that help distinguish CP from RCM include: (1) Enhanced ventricular interdependence: This is the most specific finding for CP. During inspiration, RV systolic pressure increases while LV systolic pressure decreases (ventricular discordance). In contrast, in RCM, both pressures change in the same direction (concordance); (2) Systolic area index: A ratio of the RV-to-LV systolic pressure-time area during inspiration vs expiration > 1.1 has a sensitivity of 97% and a predictive accuracy of 100% for surgically confirmed CP[51]. This measurement reflects enhanced ventricular interdependence; and (3) Pulmonary artery and aortic ejection times: The difference between aortic and pulmonary artery ejection times during expiration vs inspiration is significantly greater in patients with CP[55]. This finding is another marker of enhanced ventricular interdependence.

Cardiac catheterization is now performed infrequently. In clinical practice, particularly in resource-constraint settings, CP can often be diagnosed when there is a high clinical suspicion supported by echocardiographic evidence of constrictive physiology and CT findings of a thickened and/or calcified pericardium[35].

Role of artificial intelligence: Artificial intelligence (AI) is playing an increasingly important role in the diagnosis and management of CP. Machine learning and deep learning algorithms have been applied to TTE to identify characteristic features of CP, including pericardial thickening, abnormal intraventricular septal motion, and respiratory variation in ventricular filling. AI may also improve differentiation between CP and RCM. For example, a deep learning model based on TTE (ResNet50) differentiated CP from cardiac amyloidosis with an area under the receiver operating characteristic curve of 0.97[56]. AI-enabled ECG and central pulse wave analysis can also predict elevated diastolic filling pressures and heart failure markers non-invasively, potentially enabling earlier therapeutic intervention. In addition, AI can integrate data from electronic health records, ECGs, and multimodality imaging to develop prognostic and risk-stratification models. However, current applications remain limited by small datasets, the “black box” nature of many models, limited generalizability, potential bias, and the risk of over-reliance[57]. AI requires large, high-quality training datasets to achieve optimal performance; however, this is challenging because CP is a relatively rare disease. The “black-box” effect refers to the inability of some AI algorithms to explain how a particular diagnostic conclusion is reached. Consequently, clinical judgment remains essential when making management decisions, particularly regarding pericardiectomy. In addition, AI models may have limited generalizability because they are often trained using data from specialized tertiary care centers. Finally, excessive reliance on AI-assisted diagnostic tools may diminish physicians’ clinical examination skills and critical decision-making abilities.

Investigations to determine the etiology

CP represents the final manifestation of a wide range of pericardial insults. By the time the diagnosis is established, the initial insult may no longer be clinically apparent. Despite extensive evaluation, the underlying cause remains unidentified in 15%-20% of patients with pericardial disease[58]; however, corresponding data specific to CP are lacking. This reflects limited availability of reliable and cost-effective diagnostic tests that can facilitate timely clinical decision-making[59]. Therefore, a comprehensive approach integrating a careful clinical history with the judicious use of appropriate diagnostic modalities is essential for determining the underlying etiology of CP in individual patients.

Clinical evaluation, including a thorough history is essential. In regions where TB is endemic, TB remains the leading cause of CP; therefore, a history of current or previous pulmonary or extrapulmonary TB may suggest tuberculous CP. A history of acute pericarditis, prior cardiac surgery, or chest irradiation may indicate the underlying etiology. Systemic symptoms, such as fever, weight loss, and night sweats, may suggest TB or malignancy. Autoimmune diseases, including RA, SLE, and other connective tissue disorders, may point to an autoimmune etiology. A history of HIV infection should also be considered.

Laboratory investigations, including a complete blood count, erythrocyte sedimentation rate, and C-reactive protein level, may indicate active inflammation or infection.

TB testing: The TB skin test (TST; e.g., Mantoux test) and interferon-gamma release assays (IGRAs) may be used to evaluate patients for TB. However, both tests have limited value in regions with a high prevalence of TB because a positive result primarily reflects prior exposure to Mycobacterium tuberculosis antigens and cannot reliably distinguish active disease from latent infection[60]. Furthermore, the purified protein derivative used in the TST may yield false-positive results in individuals who have received the bacillus Calmette-Guérin (BCG) vaccine and in those sensitized to nontuberculous mycobacteria[59].

Pericardial fluid analysis: If pericardiocentesis is feasible, pericardial fluid should be sent for microbiological analysis, including polymerase chain reaction (PCR) testing and culture for bacteria, fungi, and Mycobacterium tuberculosis. Cytological examination should also be performed to detect malignant cells and evaluate for lymphomas, mesothelioma, or metastatic disease.

Pericardial biopsy: Pericardial tissue obtained during pericardiectomy should be submitted for histopathological examination to evaluate for TB and malignancy as the underlying cause of CP. Ziehl-Neelsen staining, Mycobacterium tuberculosis culture, and nucleic acid amplification testing (e.g., Xpert MTB/RIF) should also be performed.

Serology: Autoimmune serological testing should be performed when an underlying rheumatological disorder is suspected.

CMR: LGE on CMR may indicate active pericardial inflammation.

Fluorodeoxyglucose-positron emission tomography scan: Fluorodeoxyglucose-positron emission tomography (FDG-PET) is useful for identifying active pericardial inflammation, thereby helping distinguish transient, potentially reversible constriction from chronic, fixed constriction. The technique measures metabolic activity, with increased 18F-fluorodeoxyglucose uptake indicating inflammatory or tuberculous pericarditis. It may also help identify patients who are more likely to benefit from anti-inflammatory medical therapy rather than pericardiectomy[61-63].

TB as the underlying cause of pericarditis is susceptible to both overdiagnosis and underdiagnosis. This reflects the broader challenges in the diagnosis and management of TB. According to recently published data, in 2023, an estimated 2.05 million (95% uncertainty interval, 1.83-2.27 million) individuals were incorrectly diagnosed with TB (false-positives), whereas 1.00 million (0.71-1.36 million) received false-negative diagnoses. Overall, approximately three of every 10 notified TB cases may not represent true TB, while many individuals with TB remain undiagnosed because of false-negative test results[64]. The diagnosis of extrapulmonary TB is particularly challenging because obtaining appropriate specimens is often difficult and the sensitivity of current diagnostic tests is limited[65]. These limitations frequently result in an overreliance on clinical diagnosis. Bacteriological confirmation is further hindered by the paucibacillary nature of the disease. Once chronic fibrosis and calcifications have developed, postoperative tissue examination may be the only means of confirming the diagnosis. However, the diagnostic yield of pericardial histology and microbiological culture of surgical specimens is also limited. Figure 6 outlines the proposed diagnostic approach for patients with suspected CP.

Figure 6 Diagnostic approach for constrictive pericarditis and effusive-constrictive pericarditis. CP: Constrictive pericarditis; ECP: Effusive-constrictive pericarditis; SOB: Shortness of breath; JVP: Jugular venous pressure; TTE: Transthoracic echocardiography; IVC: Inferior vena cava; MV: Mitral valve; ESR: Erythrocyte sedimentation rate; CRP: C-reactive protein; CMR: Cardiac magnetic resonance.

MANAGEMENT

Before the advent of pericardiectomy, CP was managed with bed rest, fluid and salt restriction, digitalis in selected patients, and intermittent pericardiocentesis[33]. Mercurial diuretics, such as calomel and Novasurol, were used to relieve congestion[33]. In the early 20^th century, Weil and Delorme proposed “cardiolysis” as a surgical treatment for CP. This procedure involved resection of several ribs and costal cartilages over the left precordium[66]. The first successful pericardiectomy for CP was performed by the German surgeon Ludwig Rehn in 1913[67]. In the United States, the first successful pericardiectomy for CP was performed by Dr. Edward Churchill in 1928.

Treatment of CP is primarily surgical, with medical therapy playing a limited role. Diuretics may provide symptomatic relief of pulmonary and systemic congestion but can reduce cardiac output. Patients with subacute or transient CP may be treated with glucocorticoids, colchicine, or a combination of both. FDG-PET/CT has been used to predict the response to corticosteroid therapy in CP[63]. In patients with tuberculous CP, antituberculosis therapy is indicated. In tuberculous pericarditis, appropriate antituberculosis treatment may reduce the risk of progression to constriction from > 80% to < 10%[68]. Transient CP may respond to anti-inflammatory therapy and resolves in approximately 10%-20% of patients with acute pericarditis[69,70]. These patients typically have elevated C-reactive protein levels and demonstrate pericardial edema and LGE on CMR.

Pericardiectomy is the only definitive treatment with curative potential for patients with chronic, non-inflammatory CP or CP that does not respond to anti-inflammatory therapy. When feasible, radical pericardiectomy performed with cardiopulmonary bypass is the preferred surgical approach[71]. During the procedure, the pericardium is resected, often together with extensive calcific deposits (Figure 6). Pericardiectomy is a complex operation associated with substantial perioperative mortality[72]. In a multicenter European study of 81 consecutive patients (mean age 60 years; mean EuroSCORE II, 3.3%) who underwent pericardiectomy, the adjusted 10-year rates of freedom from all-cause mortality, cardiac mortality, and hospital readmission were 76.9%, 94.7%, and 90.6%, respectively[73]. A 2021 meta-analysis of 27 studies involving 2114 patients undergoing pericardiectomy for CP reported an operative mortality of 6.9% and a 5-year mortality of 32.7%. Compared with patients with idiopathic CP, those with radiation-induced and post-cardiac surgery CP had approximately threefold and twofold higher long-term mortality, respectively[74]. A more recent retrospective study from China involving 86 consecutive patients who underwent pericardiectomy reported a 30-day mortality of 5.8% and 1-year and 5-year survival rates of 88.3% and 83.5%, respectively[75].

Pericardiectomy for tuberculous CP may be technically more challenging than pericardiectomy for CP of other etiologies. A single-center retrospective study from India involving 124 patients who underwent pericardiectomy for CP reported longer operative times, greater intraoperative blood loss, and prolonged intensive care unit and hospital stays in patients with tuberculous CP, although in-hospital mortality and morbidity were not increased[25]. Patients with extensive intramyocardial fibrocalcific changes, mixed constrictive-restrictive physiology, or a high predicted perioperative mortality are unlikely to benefit from pericardiectomy[11]. In high-risk patients, performing pericardiectomy before severe constriction develops and avoiding cardiopulmonary bypass, when feasible, may improve early postoperative outcomes, whereas complete relief of cardiac constriction may improve long-term outcomes[73]. Patients with end-stage CP complicated by cachexia, malnutrition, hypoalbuminemia secondary to protein-losing enteropathy, cardiac cirrhosis, or a low cardiac index (< 1.2 L/m²/minute) are also poor candidates for pericardiectomy[50]. Recently, the World Health Organization recommended a new 4-month treatment regimen (rifapentine, isoniazid, pyrazinamide, and moxifloxacin) for drug-susceptible TB[76]. However, this regimen has not yet been evaluated in patients with tuberculous pericarditis. Figure 7 shows the gross appearance of the heart during pericardiectomy together with the excised calcified pericardium. Figure 8 outlines the proposed management approach for CP.

Figure 7 Intraoperative findings. A: Heart is encircled with calcified pericardium; B: Egg shell-like calcification.

Figure 8 Treatment approach for constrictive pericarditis. CP: Constrictive pericarditis; ESR: Erythrocyte sedimentation rate; CRP: C-reactive protein; CMR: Cardiac magnetic resonance; TB: Tuberculosis.

RECOMMENDED GUIDELINES

In recent years, interest in myopericardial diseases has increased substantially. The European Society of Cardiology (ESC) published guidelines on the diagnosis and management of pericardial diseases in 2004 and 2015[50,77]. More recently, the ESC published updated guidelines on the management of myocarditis and pericardial diseases[2]. In the same year, the American College of Cardiology (ACC) published its first expert consensus decision pathway on the diagnosis and management of pericarditis[3]. The ESC recommends multimodality imaging for all patients with suspected CP (Class I, Level of Evidence C). The ACC recommends noninvasive hemodynamic assessment with TTE for all patients and CMR to evaluate pericardial inflammation when clinically indicated.

Both societies recommend cardiac catheterization for hemodynamic assessment when multimodality imaging is inconclusive (Class IIa, Level of Evidence C, ESC). For treatment, both the ESC and ACC recommend anti-inflammatory therapy for patients with transient or newly diagnosed constrictive pericarditis associated with active pericardial inflammation, and pericardiectomy for patients with chronic constriction in the absence of active inflammation or when anti-inflammatory therapy is unsuccessful (Class I, Level of Evidence C, ESC). The ACC does not recommend partial anterior or diaphragmatic pericardiectomy for the treatment of CP.

ECP

ECP is characterized by persistent elevation of right atrial pressure after pericardiocentesis despite normalization of intrapericardial pressure. The classic hemodynamic criteria for ECP is failure of the right atrial pressure to decrease by at least 50% or to fall below 10 mmHg after pericardiocentesis[78]. Patients may initially present with cardiac tamponade; however, following pericardial drainage, constrictive physiology becomes apparent. Advances in multimodality imaging now allow a noninvasive diagnosis without the need for cardiac catheterization. The reported prevalence of ECP ranges from 2.4% to 14.8%, with a pooled estimate of 4.5%[79].

Etiology of ECP

As with chronic CP, TB is likely the most common cause of ECP in developing countries, whereas idiopathic or viral etiologies predominate in developed countries. In a systematic review by Ntsekhe et al[79] that included 642 patients with ECP diagnosed using imaging or invasive hemodynamic criteria, the reported etiologies were idiopathic or viral (58%), TB (38%), post-radiation (8%), and post-pericardiotomy (4%).

Presentation

Patients with ECP may present with features of CP, cardiac tamponade, or both. Clinical features of cardiac tamponade include hypotension, tachycardia, elevated JVP, and pulsus paradoxus, whereas constrictive physiology typically presents with fatigue, exertional dyspnea, peripheral edema, hepatomegaly, and ascites[80]. In clinical practice, persistent elevation of the JVP after pericardiocentesis should raise suspicion for ECP[81].

Diagnosis

Echocardiography is the first-line imaging modality and is typically performed both before and after pericardiocentesis. Pre-pericardiocentesis echocardiographic findings include diastolic chamber collapse, intraventricular septal shift, IVC dilation, and pericardial adhesions[4,82]. After pericardiocentesis, constrictive physiology typically becomes more apparent and is characterized by persistent elevation of right atrial pressure, unchanged mitral valve E-wave velocity, persistent hepatic vein diastolic flow reversal, and persistent respirophasic septal shift, mitral inflow variation, and IVC dilation[83].

CMR and CT play complementary roles in the evaluation of ECP. Before pericardial drainage, CMR and CT often demonstrate a pericardial effusion accompanied by pericardial thickening and/or enhancement(Figure 9). These modalities also provide valuable structural and tissue characterization, including assessment of pericardial inflammation. FDG-PET may identify reversible pericardial inflammation and thereby help identify patients who are more likely to benefit from anti-inflammatory therapy.

Figure 9 Cardiac computed tomography scan. A-C: Thickened and calcified visceral and parietal layers and pericardial effusion in the pericardial sac.

Cardiac catheterization remains the gold standard for the diagnosis of ECP and continues to play a pivotal role in diagnostically challenging cases. The invasive diagnostic criteria for ECP is failure of the right atrial pressure to fall below 10 mmHg or to decrease by at least 50% following pericardiocentesis[78]. Before pericardial drainage, cardiac catheterization may demonstrate intermediate right atrial pressure waveforms, including persistent V waves and prominent x and y descents[78]. After drainage, supportive hemodynamic findings include persistent elevation of right atrial pressure, the absence of an inspiratory decline, a prominent y descent, and a dip-and-plateau configuration of the RV pressure tracing[84].

Treatment

The management of ECP focuses on treating the underlying etiology, reducing pericardial inflammation, and relieving constrictive physiology[80,82]. The mainstays of treatment include emergency pericardiocentesis for cardiac tamponade, anti-inflammatory therapy, and pericardiectomy in selected patients. Unlike chronic CP, ECP may be reversible and respond to anti-inflammatory therapy[4]. In patients with tuberculous pericarditis, appropriate antituberculosis therapy is essential. Corticosteroids may be considered in selected high-risk patients, particularly those without HIV infection who present with evidence of constriction[68,80]. Pericardiectomy is reserved for patients with refractory symptoms despite medical therapy, intolerance to medical therapy, or chronic irreversible constriction[80].

CONCLUSION

Although CP is a well-recognized clinical entity, it remains a diagnostic challenge. Early disease is often difficult to recognize, whereas advanced CP may be mistaken for other causes of heart failure or even non-cardiac conditions. A high index of clinical suspicion is therefore essential for timely diagnosis. Advances in multimodality imaging have improved the diagnostic evaluation of CP and reduced the routine need for invasive hemodynamic assessment. Despite these advances, establishing tuberculous etiology remains challenging, particularly in resource-limited settings. Early identification of patients with inflammatory CP has expanded the role of anti-inflammatory therapy. However, pericardiectomy remains the only definitive treatment for patients with chronic, irreversible CP. The development of dedicated multidisciplinary pericardial disease centers may further improve the diagnosis, management, and outcomes of patients with CP.