The correct answer is: E. Refer for pericardiectomy

Overall, imaging findings are consistent with calcific constrictive pericarditis with no active inflammation of the pericardium (Figures 1 and 2).

Figure 2

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Figure 2

Discussion

This patient's clinical history, features and imaging findings are consistent with chronic constrictive pericarditis. Constrictive pericarditis manifests as impaired diastolic filling of the ventricles.¹ In constrictive pericarditis, symptoms are often insidious, with progressive signs and symptoms of right-sided heart failure, such as fatigue, peripheral edema and dyspnea, as the patient above. The most common reported causes are idiopathic/viral (42 – 49%), post-cardiac surgery (11-37%), post-radiation (9-31%), connective tissue disorder (3-7%), post-infectious (3-6%, either tuberculosis or purulent pericarditis), and miscellaneous causes (10%), such as malignancy, trauma, drug-induced, asbestosis, sarcoidosis and uremic pericarditis.¹

A diagnostic suspicion of constrictive pericarditis is usually raised by symptoms and signs of right heart failure, with or without accompanying history of an inciting pericardial disease. Physical exam findings can include Kussmaul's sign, which is the failure of an appropriate fall or paradoxical rise in jugular venous pressure (JVP) during inspiration. This happens due to high pressures in an encased right atrium, that are resistant to the flow through the superior vena cava during inspiration. The "pericardial knock" is the high-pitched sound audible in early diastole from sudden cessation of rapid ventricular filling.^1,2

Multiple diagnostic tools can aid in defining constrictive pericarditis, although clinical suspicion is always paramount. ECG can show low voltages, non-specific ST/T changes (as in this patient case), or atrial fibrillation. Chest X-ray can show pericardial calcifications in one-third of the cases.¹ CT and MRI have an important role. Pericardial thickness > 3-4mm can be seen on both. On CT, pericardial calcifications can be also seen, given that this modality is the most accurate imaging technique to identify calcified tissue.¹ Furthermore, although the diagnosis of constrictive pericarditis can often be made with a thorough history, physical exam and a chest X-ray, identifying active inflammation and/or a potentially reversible cause of constrictive pericarditis requires pericardial characterization by cardiovascular magnetic resonance (CMR). On CMR, specifically using dark blood, bright blood cines, T2STIR (edema) based sequence, and delayed hyper-enhancement sequences, we can identify a thickened pericardium, features of constrictive physiology, pericardial edema and pericardial inflammation respectively.³ Ventricular interdependence may be observed with real-time cine imaging.^1,3

The presence of calcium on imaging suggests a chronic calcific pericardial process, though excluding inflammation is important and can, in some cases, save the patient a pericardiectomy in the setting of "transient constrictive pericarditis". Further, absence of inflammation during a pericardiectomy has important surgical/technical implications, with less inflammation being more favorable at the time of surgery.⁴

Although not always required, left and right cardiac catheterization remains the gold standard to evaluate for the presence and hemodynamic significance of constriction, and also to differentiate constrictive to restrictive heart disease in circumstances of uncertain diagnosis (e.g. radiation heart disease). It is indicated (Class I-C) when non-invasive diagnostic methods do not provide definite diagnosis of constriction.¹ In cardiac catheterization, constrictive physiology will show an equalization of right and left cardiac pressures, a rapid "y" descent on atrial pressure waveforms, and a "square root" or "dip and plateau" sign on ventricular pressure waveforms. Ventricular diastolic pressures are high but stroke volume is low because of insufficient pre-load.^1,2,5 Additionally, there is isolation of the cardiac chambers from variations in intra-thoracic pressures during the respiratory cycle. Ventricular interdependence is assessed by systolic area index, which is the change in the ventricular pressure area between inspiration and expiration. A systolic area index above 1.1 has been shown to be predictive of constrictive pericarditis, with 97% sensitivity and 100% specificity in surgically proven patients.^1,5

The recommended treatment for chronic permanent constriction is complete surgical resection of the pericardium (radical pericardiectomy). In some cases, if there is evidence of extensive pericardial inflammation and suggestion of a more early/acute phase of the illness, a trial of anti-inflammatory therapy and symptom management may be reasonable, with assessment for reversibility within three months.^4,6,7 This may preclude the need for surgery, or reduce the technical difficulty of future surgery by resolving underlying inflammation.

Medical therapy may have a role in at least three conditions:

1. Treat underlying etiology if reversible (i.e. tuberculosis, to reduce risk of progression to constriction)
2. Treat underlying inflammation to resolve transient constriction (as evidenced by elevated inflammatory markers and imaging findings) – treatments include colchicine, NSAIDS, prednisone, etc.^1,6,7
3. Symptomatic management of right heart failure (i.e. diuretics)

It is important to keep in mind that, if pericardiectomy is possible, medical therapy should not delay the procedure, unless surgery is high risk or contraindicated.

Based on this case, the patient appears to have developed chronic constrictive pericarditis over time, possibly since her first presentation for palpitations, hypotension and edema, two years before referral to pericardiectomy. Furthermore, supporting imaging findings of a significant calcium burden (CT and chest X-ray, constrictive physiology by echo, MRI and catheterization, with negative inflammatory biomarkers (CRP and WSR) along with no signs of pericardial inflammation on CMR suggested a more chronic course. Most importantly, right heart failure resulting in underlying cirrhosis, with established portal hypertension and thrombocytopenia, meant that referral for pericardiectomy was the most appropriate course of management before she developed more significant liver dysfunction, which would have precluded surgery. She underwent successful pericardiectomy two months after presentation and continued to do well after surgery, completing cardiac rehabilitation. Diuretics were progressively tapered off and her platelet count stabilized. She continues to do well months after the procedure.

References

1. Adler Y, Charron P, Imazio M, et al. The 2015 ESC guidelines on the diagnosis and management of pericardial diseases. Eur Heart J 2015;36:2921-64.
2. Geske JB, Anavekar NS, Nishimura RA, Oh JK, Gersh BJ. Differentiation of constriction and restriction: complex cardiovascular hemodynamics. J Am Coll Cardiol 2016;68:2329-47.
3. Chetrit M, Xu B, Kwon DH, et al. Imaging-guided therapies for pericardial diseases. JACC Cardiovasc Imaging 2019. [Epub ahead of print].
4. Unai S, Johnston DR. Radical pericardiectomy for pericardial diseases. Curr Cardiol Rep 2019;21:6.
5. Talreja DR, Nishimura RA, Oh JK, Holmes DR. Constrictive pericarditis in the modern era: novel criteria for diagnosis in the cardiac catheterization laboratory. J Am Coll Cardiol 2008;51:315-9.
6. Haley JH, Tajik AJ, Danielson GK, Schaff HV, Mulvagh SL, Oh JK. Transient constrictive pericarditis: causes and natural history. J Am Coll Cardiol 2004;43:271-5.
7. Cremer PC, Kumar A, Kontzias A, et al. Complicated pericarditis: understanding risk factors and pathophysiology to inform imaging and treatment. J Am Coll Cardiol 2016;68:2311-28.