International Journal of Cardiology 184 (2015) 302–305
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Treatment of refractory enterovirus effusive-constrictive pericarditis with corticosteroids Frederick M. Howard, Akshar Y. Patel ⁎ Department of Medicine, University of Michigan Health System and Medical School, Ann Arbor, MI, United States
a r t i c l e
i n f o
Article history: Received 2 January 2015 Accepted 21 February 2015 Available online 24 February 2015 Keywords: Enterovirus Effusive pericarditis Constrictive pericarditis Corticosteroids
A 33-year-old man presented to the emergency department with one week of fever, malaise, sinus congestion, and cough. He had no significant medical, surgical, family, or social history, and was previously on no medications. He did report contacts at work with upper respiratory tract infection symptoms. Three days prior to admission, he was prescribed amoxicillin by his primary care provider for possible bacterial sinusitis, and also started guaifenesin and ibuprofen. However, this failed to address his symptoms, and he returned to the clinic the morning of admission. He was noted to have a new systolic murmur, an EKG was found to be normal, and the patient was then sent home on azithromycin, with instructions to return for fever N 100.5. At home, he spiked a temperature to 102 F, and had an episode of pre-syncope with dizziness and nausea, and he then presented to the emergency department. In the ED, vitals included temperature of 100.4 F, blood pressure of 98/62 mm Hg, heart rate of 107 beats/minute, and respiratory rate of 20 breaths/minute. Exam revealed a pericardial friction rub, positive pulsus paradoxus to 18–20 mm Hg, positive Kussmaul's sign, and abrogation of radial pulse with Valsalva. Initial labs were notable for a normocytic anemia with hemoglobin of 10.1 g/dL, white blood cell count of 6.4/nL, mild elevation of AST and ALT (66 and 84 IU/L respectively), CRP of 9.7 mg/dL and ESR of 62 mm. Chest X-ray revealed small pleural effusions and a mildly enlarged cardiomediastinal
⁎ Corresponding author at: Department of Medicine, 1500 East Medical Center Drive, Ann Arbor, MI 48109, United States. E-mail address: [email protected] (A.Y. Patel).
http://dx.doi.org/10.1016/j.ijcard.2015.02.030 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
silhouette. Echocardiogram revealed a large pericardial effusion with no chamber collapse, but with respirophasic mitral valve inflow, LVOT/AV Doppler variation, and plethoric noncollapsible IVC concerning for early tamponade (Fig. 1). A pericardial drain was then placed, and initial analysis of the pericardial fluid revealed an RBC count of 284,000 cells/mm2, WBC count of 2717 cells/mm2 with 71% neutrophils, LDH of 746 IU/L, and protein of 5.2 g/dL. An extensive evaluation was performed, ultimately resulting in the isolation of enterovirus via a viral culture of the pericardial fluid. The remained of the workup was negative. Notably, coxsackie A and B serologies were negative. The drain was removed after six days, and he was then started on ibuprofen and colchicine. Repeat echocardiogram revealed findings consistent with effusive — constrictive pericarditis (Fig. 2). The patient was discharged, but returned to the ED for incessant cough and continued fevers. Due to evidence of persistent constriction on echocardiogram, he was transitioned from ibuprofen to aspirin, but he continued to experience fevers, chills, and headaches. Cardiac MRI revealed diffuse thickening of the pericardium (Fig. 3) with evidence of constriction on cine images. Given the lack of response to approximately two weeks of initial medical therapy, the decision was made to add 1 mg/kg prednisone to his medication regimen, with a taper of 10 mg/month. Follow-up at 1 week from the initiation of prednisone revealed no effusion or evidence of constriction and marked improvement in symptoms. He has since completed several months of his taper without incident, and repeat cardiac MRI has confirmed resolution of pericardial thickening with no evidence of constrictive physiology. This case of enterovirus effusive-constrictive pericarditis highlights several important points in the diagnosis of pericardial disease, and inspires questions with regard to the management of this entity. This is especially true given the recent emergency of enterovirus D68 causing respiratory symptoms very similar to those afflicting our patient [1,2] Although pericarditis is often attributed to a viral infection, the determination of a specific viral cause is uncommon [3,4]. Furthermore, the viral etiology of a case of pericarditis is most often inferred from serologic studies; isolation from pericardial fluid or tissue is rare [5]. Specific etiologies are more likely to be identified in patients such as ours who develop large effusions or cardiac tamponade [3], as there is a increased diagnostic yield of therapeutic pericardiocentesis for tamponade or hemodynamic derangement [3,6]. Acute pericarditis has a diverse natural history, ranging from resolution with first-line therapy to the development of constriction with or without effusion. Transient cardiac constriction has been reported in
F.M. Howard, A.Y. Patel / International Journal of Cardiology 184 (2015) 302–305
303
Fig. 1. Transthoracic echocardiogram. Respirophasic variation in mitral valve inflow and plethoric inferior vena cava, without inspiratory collapse.
several studies of patients with idiopathic pericarditis, with resolution averaging from 2 to 9 months [7,8]. It is postulated that constriction is the result of edema, fibrin deposition, or inflammation from pericarditis [9]. Overall, approximately 1% of patients with idiopathic pericarditis require pericardiectomy [10]. The risk does not appear elevated in patients who develop constriction after the resolution of effusion following an episode of effusive pericarditis, as one series followed 16 such patients, none of whom required pericardiectomy [9]. However, pericardiectomy is a frequent outcome in patients with effusive-constrictive pericarditis [10]. This uncommon sequela of acute pericarditis is most often idiopathic [11], and is postulated to represent an intermediate on the spectrum from acute pericarditis to constrictive
pericarditis [12]. In a study of 1184 patients with pericarditis by Sagristà-Sauleda et al., 18% had clinical tamponade, and 1% had effusive-constrictive pericarditis. In the 7 patients with idiopathic effusive-constrictive pericarditis, 4 required pericardiectomy [10]. NSAIDs, aspirin, and colchicine remain the standard of care for the treatment of idiopathic or viral acute pericarditis [13,14]. Corticosteroid treatment can yield rapid response in acute pericarditis, but several studies have raised concern about risk of recurrence following such therapy, although evidence is still limited [9]. It is postulated that corticosteroids suppress clearance of the underlying virus and thus promote recurrence. Although there is considerable hesitancy to treat acute pericarditis with steroids, there are reports of definitive resolution of
304
F.M. Howard, A.Y. Patel / International Journal of Cardiology 184 (2015) 302–305
Fig. 3. Cardiac MRI: Extensive diffuse heterogeneous thickening of the pericardium, measuring up to 16 mm along the free wall of the right ventricle. Linear areas of low signal in the pericardium representing fibrin. In cine images (not shown) there is evidence of abnormal shift of the intraventricular septum consistent with evidence of constriction.
Conflict of interest Fig. 2. Transthoracic echocardiogram. Small pericardial effusion with fibrinous material in the pericardial space, respirophasic mitral valve inflow velocities, and M-mode showing early diastolic bounce (arrows) and septal deviation with inspiration.
The authors report no relationships that could be construed as a conflict of interest.
References effusive-constrictive pericarditis with the administration of corticosteroids [15–17]. As shown here, the role of steroids in the prevention of progressive pericardial fibrosis and constriction in patients with effusive-constrictive pericarditis may be promising and requires further evaluation. Effusive-constrictive pericarditis remains a rare but increasingly recognized sequela of acute viral pericarditis. Definitive treatment approaches are not well elucidated, but given the frequency of progression to pericardial constriction, close follow-up and appropriate adjustment of therapy is warranted.
[1] J. Stephenson, CDC tracking enterovirus D-68 outbreak causing severe respiratory illness in children in the Midwest, JAMA 312 (13) (Oct 1 2014) 1290. [2] C.M. Midgley, M.A. Jackson, R. Selvarangan, G. Turabelidze, E. Obringer, D. Johnson, B.L. Giles, A. Patel, F. Echols, M.S. Oberste, W.A. Nix, J.T. Watson, S.I. Gerber, Severe respiratory illness associated with enterovirus D68 — Missouri and Illinois, 2014, MMWR Morb. Mortal. Wkly Rep. 63 (36) (Sep 12 2014) 798–799. [3] G. Permanyer-Miralda, J. Sagristá-Sauleda, J. Soler-Soler, Primary acute pericardial disease: a prospective series of 231 consecutive patients, Am. J. Cardiol. 56 (10) (Oct 1 1985) 623–630. [4] S. Ben-Horin, I. Bank, V. Guetta, A. Livneh, Large symptomatic pericardial effusion as the presentation of unrecognized cancer: a study in 173 consecutive patients undergoing pericardiocentesis, Medicine (Baltimore) 85 (1) (Jan 2006) 49–53. [5] J.F. Woodruff, Viral myocarditis. A review, Am. J. Pathol. 101 (2) (1980) 425–484.
F.M. Howard, A.Y. Patel / International Journal of Cardiology 184 (2015) 302–305 [6] J. Sagristà-Sauleda, A.S. Mercé, J. Soler-Soler, Diagnosis and management of pericardial effusion, World J. Cardiol. 3 (5) (2011) 135–143. http://dx.doi.org/10.4330/wjc. v3.i5.135. [7] Transient Constrictive Pericarditis: Causes and Natural History John H. Haley, MD, FACC,* A. Jamil Tajik, MD, FACC,* Gordon K. Danielson, MD, FACC,† Hartzell V. Schaff, MD, FACC,† Sharon L. Mulvagh, MD, FACC,* Jae K. Oh, MD, FACC* [8] J. Sagrista-Sauleda, G. Permanyer-Miralda, J. Candell-Riera, J. Angel, J. Soler-Soler, Transient cardiac constriction: an unrecognized pattern of evolution in effusive acute idiopathic pericarditis, Am. J. Cardiol. 59 (1987) 961–966. [9] J. Sagristà Sauleda, G. Permanyer Miralda, J. Soler Soler, Diagnosis and management of acute pericardial syndromes, Rev. Esp. Cardiol. 58 (7) (Jul 2005) 830–841. [10] M. Lotrionte, G. Biondi-Zoccai, M. Imazio, D. Castagno, C. Moretti, A. Abbate, P. Agostoni, A.L. Brucato, P. Di Pasquale, M. Raatikka, G. Sangiorgi, A. Laudito, I. Sheiban, F. Gaita, International collaborative systematic review of controlled clinical trials on pharmacologic treatments for acute pericarditis and its recurrences, Am. Heart J. 160 (4) (Oct 2010) 662–670. [11] J. Sagristà-Sauleda, J. Angel, A. Sánchez, G. Permanyer-Miralda, J. Soler-Soler, Effusive-constrictive pericarditis, N. Engl. J. Med. 350 (5) (Jan 29 2004) 469–475.
305
[12] E.W. Hancock, A clearer view of effusive-constrictive pericarditis, N. Engl. J. Med. 350 (5) (Jan 29 2004) 435–437. [13] M. Imazio, M. Bobbio, E. Cecchi, D. Demarie, B. Demichelis, F. Pomari, M. Moratti, G. Gaschino, M. Giammaria, A. Ghisio, R. Belli, R. Trinchero, Colchicine in addition to conventional therapy for acute pericarditis: results of the COlchicine for acute PEricarditis (COPE) trial, Circulation 112 (13) (Sep 27 2005) 2012–2016. [14] L. Chhabra, D.H. Spodick, Is recurrent pericarditis a risk for constrictive evolution? Int. J. Cardiol. 177 (1) (Nov 15 2014) 139. [15] A. Samara, M. Bergman, J. Vitrai, Z.Z. Brener, H. Salman, Recovery of transient pericardial constriction following steroid administration, Heart Lung Circ. 19 (8) (Aug 2010) 470–472. http://dx.doi.org/10.1016/j.hlc.2010.04.131. [16] C. Massardier, C. Dauphin, R. Eschalier, J.R. Lusson, M. Soubrier, Resistant or recurrent acute pericarditis: a new therapeutic opportunity? Int. J. Cardiol. 177 (2) (Dec 15 2014) e75–e77. [17] A. Brucato, M. Imazio, S. Curri, G. Palmieri, R. Trinchero, Medical treatment of pericarditis during pregnancy, Int. J. Cardiol. 144 (3) (Oct 29 2010) 413–414.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Treatment of refractory enterovirus effusive-constrictive pericarditis with corticosteroids Frederick M. Howard, Akshar Y. Patel ⁎ Department of Medicine, University of Michigan Health System and Medical School, Ann Arbor, MI, United States
a r t i c l e
i n f o
Article history: Received 2 January 2015 Accepted 21 February 2015 Available online 24 February 2015 Keywords: Enterovirus Effusive pericarditis Constrictive pericarditis Corticosteroids
A 33-year-old man presented to the emergency department with one week of fever, malaise, sinus congestion, and cough. He had no significant medical, surgical, family, or social history, and was previously on no medications. He did report contacts at work with upper respiratory tract infection symptoms. Three days prior to admission, he was prescribed amoxicillin by his primary care provider for possible bacterial sinusitis, and also started guaifenesin and ibuprofen. However, this failed to address his symptoms, and he returned to the clinic the morning of admission. He was noted to have a new systolic murmur, an EKG was found to be normal, and the patient was then sent home on azithromycin, with instructions to return for fever N 100.5. At home, he spiked a temperature to 102 F, and had an episode of pre-syncope with dizziness and nausea, and he then presented to the emergency department. In the ED, vitals included temperature of 100.4 F, blood pressure of 98/62 mm Hg, heart rate of 107 beats/minute, and respiratory rate of 20 breaths/minute. Exam revealed a pericardial friction rub, positive pulsus paradoxus to 18–20 mm Hg, positive Kussmaul's sign, and abrogation of radial pulse with Valsalva. Initial labs were notable for a normocytic anemia with hemoglobin of 10.1 g/dL, white blood cell count of 6.4/nL, mild elevation of AST and ALT (66 and 84 IU/L respectively), CRP of 9.7 mg/dL and ESR of 62 mm. Chest X-ray revealed small pleural effusions and a mildly enlarged cardiomediastinal
⁎ Corresponding author at: Department of Medicine, 1500 East Medical Center Drive, Ann Arbor, MI 48109, United States. E-mail address: [email protected] (A.Y. Patel).
http://dx.doi.org/10.1016/j.ijcard.2015.02.030 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
silhouette. Echocardiogram revealed a large pericardial effusion with no chamber collapse, but with respirophasic mitral valve inflow, LVOT/AV Doppler variation, and plethoric noncollapsible IVC concerning for early tamponade (Fig. 1). A pericardial drain was then placed, and initial analysis of the pericardial fluid revealed an RBC count of 284,000 cells/mm2, WBC count of 2717 cells/mm2 with 71% neutrophils, LDH of 746 IU/L, and protein of 5.2 g/dL. An extensive evaluation was performed, ultimately resulting in the isolation of enterovirus via a viral culture of the pericardial fluid. The remained of the workup was negative. Notably, coxsackie A and B serologies were negative. The drain was removed after six days, and he was then started on ibuprofen and colchicine. Repeat echocardiogram revealed findings consistent with effusive — constrictive pericarditis (Fig. 2). The patient was discharged, but returned to the ED for incessant cough and continued fevers. Due to evidence of persistent constriction on echocardiogram, he was transitioned from ibuprofen to aspirin, but he continued to experience fevers, chills, and headaches. Cardiac MRI revealed diffuse thickening of the pericardium (Fig. 3) with evidence of constriction on cine images. Given the lack of response to approximately two weeks of initial medical therapy, the decision was made to add 1 mg/kg prednisone to his medication regimen, with a taper of 10 mg/month. Follow-up at 1 week from the initiation of prednisone revealed no effusion or evidence of constriction and marked improvement in symptoms. He has since completed several months of his taper without incident, and repeat cardiac MRI has confirmed resolution of pericardial thickening with no evidence of constrictive physiology. This case of enterovirus effusive-constrictive pericarditis highlights several important points in the diagnosis of pericardial disease, and inspires questions with regard to the management of this entity. This is especially true given the recent emergency of enterovirus D68 causing respiratory symptoms very similar to those afflicting our patient [1,2] Although pericarditis is often attributed to a viral infection, the determination of a specific viral cause is uncommon [3,4]. Furthermore, the viral etiology of a case of pericarditis is most often inferred from serologic studies; isolation from pericardial fluid or tissue is rare [5]. Specific etiologies are more likely to be identified in patients such as ours who develop large effusions or cardiac tamponade [3], as there is a increased diagnostic yield of therapeutic pericardiocentesis for tamponade or hemodynamic derangement [3,6]. Acute pericarditis has a diverse natural history, ranging from resolution with first-line therapy to the development of constriction with or without effusion. Transient cardiac constriction has been reported in
F.M. Howard, A.Y. Patel / International Journal of Cardiology 184 (2015) 302–305
303
Fig. 1. Transthoracic echocardiogram. Respirophasic variation in mitral valve inflow and plethoric inferior vena cava, without inspiratory collapse.
several studies of patients with idiopathic pericarditis, with resolution averaging from 2 to 9 months [7,8]. It is postulated that constriction is the result of edema, fibrin deposition, or inflammation from pericarditis [9]. Overall, approximately 1% of patients with idiopathic pericarditis require pericardiectomy [10]. The risk does not appear elevated in patients who develop constriction after the resolution of effusion following an episode of effusive pericarditis, as one series followed 16 such patients, none of whom required pericardiectomy [9]. However, pericardiectomy is a frequent outcome in patients with effusive-constrictive pericarditis [10]. This uncommon sequela of acute pericarditis is most often idiopathic [11], and is postulated to represent an intermediate on the spectrum from acute pericarditis to constrictive
pericarditis [12]. In a study of 1184 patients with pericarditis by Sagristà-Sauleda et al., 18% had clinical tamponade, and 1% had effusive-constrictive pericarditis. In the 7 patients with idiopathic effusive-constrictive pericarditis, 4 required pericardiectomy [10]. NSAIDs, aspirin, and colchicine remain the standard of care for the treatment of idiopathic or viral acute pericarditis [13,14]. Corticosteroid treatment can yield rapid response in acute pericarditis, but several studies have raised concern about risk of recurrence following such therapy, although evidence is still limited [9]. It is postulated that corticosteroids suppress clearance of the underlying virus and thus promote recurrence. Although there is considerable hesitancy to treat acute pericarditis with steroids, there are reports of definitive resolution of
304
F.M. Howard, A.Y. Patel / International Journal of Cardiology 184 (2015) 302–305
Fig. 3. Cardiac MRI: Extensive diffuse heterogeneous thickening of the pericardium, measuring up to 16 mm along the free wall of the right ventricle. Linear areas of low signal in the pericardium representing fibrin. In cine images (not shown) there is evidence of abnormal shift of the intraventricular septum consistent with evidence of constriction.
Conflict of interest Fig. 2. Transthoracic echocardiogram. Small pericardial effusion with fibrinous material in the pericardial space, respirophasic mitral valve inflow velocities, and M-mode showing early diastolic bounce (arrows) and septal deviation with inspiration.
The authors report no relationships that could be construed as a conflict of interest.
References effusive-constrictive pericarditis with the administration of corticosteroids [15–17]. As shown here, the role of steroids in the prevention of progressive pericardial fibrosis and constriction in patients with effusive-constrictive pericarditis may be promising and requires further evaluation. Effusive-constrictive pericarditis remains a rare but increasingly recognized sequela of acute viral pericarditis. Definitive treatment approaches are not well elucidated, but given the frequency of progression to pericardial constriction, close follow-up and appropriate adjustment of therapy is warranted.
[1] J. Stephenson, CDC tracking enterovirus D-68 outbreak causing severe respiratory illness in children in the Midwest, JAMA 312 (13) (Oct 1 2014) 1290. [2] C.M. Midgley, M.A. Jackson, R. Selvarangan, G. Turabelidze, E. Obringer, D. Johnson, B.L. Giles, A. Patel, F. Echols, M.S. Oberste, W.A. Nix, J.T. Watson, S.I. Gerber, Severe respiratory illness associated with enterovirus D68 — Missouri and Illinois, 2014, MMWR Morb. Mortal. Wkly Rep. 63 (36) (Sep 12 2014) 798–799. [3] G. Permanyer-Miralda, J. Sagristá-Sauleda, J. Soler-Soler, Primary acute pericardial disease: a prospective series of 231 consecutive patients, Am. J. Cardiol. 56 (10) (Oct 1 1985) 623–630. [4] S. Ben-Horin, I. Bank, V. Guetta, A. Livneh, Large symptomatic pericardial effusion as the presentation of unrecognized cancer: a study in 173 consecutive patients undergoing pericardiocentesis, Medicine (Baltimore) 85 (1) (Jan 2006) 49–53. [5] J.F. Woodruff, Viral myocarditis. A review, Am. J. Pathol. 101 (2) (1980) 425–484.
F.M. Howard, A.Y. Patel / International Journal of Cardiology 184 (2015) 302–305 [6] J. Sagristà-Sauleda, A.S. Mercé, J. Soler-Soler, Diagnosis and management of pericardial effusion, World J. Cardiol. 3 (5) (2011) 135–143. http://dx.doi.org/10.4330/wjc. v3.i5.135. [7] Transient Constrictive Pericarditis: Causes and Natural History John H. Haley, MD, FACC,* A. Jamil Tajik, MD, FACC,* Gordon K. Danielson, MD, FACC,† Hartzell V. Schaff, MD, FACC,† Sharon L. Mulvagh, MD, FACC,* Jae K. Oh, MD, FACC* [8] J. Sagrista-Sauleda, G. Permanyer-Miralda, J. Candell-Riera, J. Angel, J. Soler-Soler, Transient cardiac constriction: an unrecognized pattern of evolution in effusive acute idiopathic pericarditis, Am. J. Cardiol. 59 (1987) 961–966. [9] J. Sagristà Sauleda, G. Permanyer Miralda, J. Soler Soler, Diagnosis and management of acute pericardial syndromes, Rev. Esp. Cardiol. 58 (7) (Jul 2005) 830–841. [10] M. Lotrionte, G. Biondi-Zoccai, M. Imazio, D. Castagno, C. Moretti, A. Abbate, P. Agostoni, A.L. Brucato, P. Di Pasquale, M. Raatikka, G. Sangiorgi, A. Laudito, I. Sheiban, F. Gaita, International collaborative systematic review of controlled clinical trials on pharmacologic treatments for acute pericarditis and its recurrences, Am. Heart J. 160 (4) (Oct 2010) 662–670. [11] J. Sagristà-Sauleda, J. Angel, A. Sánchez, G. Permanyer-Miralda, J. Soler-Soler, Effusive-constrictive pericarditis, N. Engl. J. Med. 350 (5) (Jan 29 2004) 469–475.
305
[12] E.W. Hancock, A clearer view of effusive-constrictive pericarditis, N. Engl. J. Med. 350 (5) (Jan 29 2004) 435–437. [13] M. Imazio, M. Bobbio, E. Cecchi, D. Demarie, B. Demichelis, F. Pomari, M. Moratti, G. Gaschino, M. Giammaria, A. Ghisio, R. Belli, R. Trinchero, Colchicine in addition to conventional therapy for acute pericarditis: results of the COlchicine for acute PEricarditis (COPE) trial, Circulation 112 (13) (Sep 27 2005) 2012–2016. [14] L. Chhabra, D.H. Spodick, Is recurrent pericarditis a risk for constrictive evolution? Int. J. Cardiol. 177 (1) (Nov 15 2014) 139. [15] A. Samara, M. Bergman, J. Vitrai, Z.Z. Brener, H. Salman, Recovery of transient pericardial constriction following steroid administration, Heart Lung Circ. 19 (8) (Aug 2010) 470–472. http://dx.doi.org/10.1016/j.hlc.2010.04.131. [16] C. Massardier, C. Dauphin, R. Eschalier, J.R. Lusson, M. Soubrier, Resistant or recurrent acute pericarditis: a new therapeutic opportunity? Int. J. Cardiol. 177 (2) (Dec 15 2014) e75–e77. [17] A. Brucato, M. Imazio, S. Curri, G. Palmieri, R. Trinchero, Medical treatment of pericarditis during pregnancy, Int. J. Cardiol. 144 (3) (Oct 29 2010) 413–414.
