International Journal of Cardiology 176 (2014) 1158–1160
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Chronic constrictive pericarditis in general adult population Ville Kytö a,d,⁎, Jussi Sipilä b,e, Päivi Rautava c,f a
Heart Center, Turku University Hospital, Turku, Finland Clinical Neurosciences, Neurology, Turku University Hospital, Turku, Finland c Clinical Research Center, Turku University Hospital, Turku, Finland d PET Center, University of Turku, Turku, Finland e Neurology, University of Turku, Turku, Finland f Public Health, University of Turku, Turku, Finland b
a r t i c l e
i n f o
Article history: Received 18 July 2014 Accepted 27 July 2014 Available online 4 August 2014 Keywords: Pericardial disease Pericarditis Constriction
Pericarditis is commonly an acute self-limiting virus triggered disease with good prognosis but when persistent it may lead to rigid and constricted pericardial sac resulting to constriction [1]. Etiology of constriction is mainly tuberculosis in Africa and developing countries, but acute pericarditis, post-surgical constriction, neoplasms, and other systemic diseases are main contemporary causes in the western countries [2]. Although a number of patient series of constriction have been published, there are however no studies on all-comer chronic constrictive pericarditis patients at population level. We studied occurrence, characteristics, and long-term outcome of chronic constrictive pericarditis in general adult population. All patients aged ≥18 years admitted to hospital between May 1st 2000 and October 31st 2009 with chronic constrictive pericarditis were identified from 29 hospitals by using the Finnish Hospital Discharge Register. Patients were followed for potential in-hospital mortality until the end of study period (median follow-up among survivors was 4.8 years, range 0.2–9.5 years). Primary discharge diagnosis of the last admissions ending in death was considered as the cause of death. Incidence was calculated using age- and sex-matched population data from the study period (38,402,024 person-years) obtained from Statistics Finland. The study was conducted according to the National Institute for Health and Welfare permission (THL/1576/5.05.00/2010).
⁎ Corresponding author at: Heart Center, Turku University Hospital, POB 52, FI-20521 Turku, Finland. Fax: +358 23137206. E-mail address: ville.kyto@utu.fi (V. Kytö).
http://dx.doi.org/10.1016/j.ijcard.2014.07.257 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Frequency and incidence were analyzed using Poisson regression models. In-hospital mortality was studied using exact Cox-regression model. Multivariate mortality model included patient characteristics associated with mortality at the p level b0.05 in univariate analysis. Total incidence rates were adjusted directly with the European standard population 2013. The SAS system version 9.3 (SAS Institute Inc., Cary, NC, USA) was used for statistical analyses. The study period included 713 hospital admissions occurring to 123 patients with constrictive pericarditis. Majority of patients were male (63.4%; CI 50.1–79.1% vs. 36.6%; CI 26.7–49.0%) with age-adjusted likelihood ratio of 1.73 (CI 1.20–2.50, p = 0.003) for male sex. Although constrictive pericarditis occurred in all age groups, 80.5% of patients were aged 50– 79 years (Fig. 1). Male patients were significantly younger than their counterparts (mean 61.2± 12.4 vs. 68.1 ±13.8 years, pb 0.0001). Incidencewas low(5.85[CI0.30–1.02]/1,000,000) in populationaged20–49,butincreased progressively from 50 to 79 years (Fig. 1). Standardized incidence was 3.44 (CI 2.88–4.08)/1,000,000 overall, 4.47 (CI 3.56–5.54) in men, and 2.42 (CI 1.79–3.21) in women. Men had an age-adjusted relative risk of 2.28 (CI 1.57–3.31; p b 0.0001) for constrictive pericarditis compared to their counterparts in general population. Atrial fibrillation (AF), congestive heart failure, and coronary artery disease were common in patients with constrictive pericarditis (Table 1). Atrial fibrillation was present in 39.8% of patients. In addition, 9.5% of patients in sinus rhythm developed AF during follow-up. Of potential etiologies, rheumatoid arthritis was present in 5.7%, malignancy in 4.1%, and tuberculosis in 0.8% of patients (Table 1). Majority (71.4%) of patients with rheumatoid arthritis had seropositive disease. Of patients with cancer, two (40%) had lung cancer, one (20%) melanoma, one gastric cancer and one chronic lymphocytic leukemia. Cardiac surgery had been performed to 4.9% of patients and 0.8% had previous rheumatic fever. None of the patients had diagnosed HIV, amyloidosis, carcinoid syndrome, or systemic connective tissue disease. Mortality rate during the follow-up period was 15.4% (CI 11.4– 29.7%) with median survival time of 112 days (Fig. 1) and twelvemonth survival of 88.6%. Factors associated with mortality in univariate analysis were age (HR 1.62; CI 1.04–2.52; p = 0.035 per 10-year increase) and renal insufficiency (HR 10.30, CI 1.44–74.80, p = 0.020). Potential etiologies or sex were not associated with death. In multivariate Cox analysis, renal insufficiency was an independent predictor of mortality (HR 7.76, CI 1.08–55.61, p = 0.04), while age had a borderline association with mortality (HR 1.58, CI 0.99–2.53; p = 0.055).
V. Kytö et al. / International Journal of Cardiology 176 (2014) 1158–1160
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Table 1 Co-morbidities and potential etiologies of constrictive pericarditis. Co-morbidity
N (total 123)
% (95% CI)
Atrial fibrillation Congestive heart failure Coronary artery disease Hypertension Diabetes Rheumatoid arthritis Previous cardiac surgery Malignancy Chronic pulmonary disease Hepatic disease/insufficiency Renal insufficiency Tuberculosis Previous rheumatic fever
49 39 33 17 10 7 6 5 5 5 2 1 1
39.8 (36.2–64.8) 31.7 (27.7–53.3) 26.8 (22.7–46.3) 13.8 (9.9–27.2) 8.1 (4.8–18.4) 5.7 (2.8–14.4) 4.9 (2.2–13.1) 4.1 (1.6–11.7) 4.1 (1.6–11.7) 4.1 (1.6–11.7) 1.6 (0.2–7.2) 0.8 (0.03–5.6) 0.8 (0.03–5.6)
pericarditis in general population. Reasons of sex predisposition are unclear, but experimental viral studies of myocardial inflammation have highlighted some potential mechanisms [5]. Sex hormones affect the risk for cardiac inflammation as progesterone and testosterone aggravate cardiac inflammation while estrogen has inhibitory effects [5]. Chronic constriction leads to increased atrial pressures and left atrial dilatation increasing the risk of AF [6]. We found the burden of AF to be significantly higher than the previously reported [3,6,7], as 40% of patients had AF at the baseline, and 10% of patients in sinus rhythm at baseline developed AF during follow-up. The risk of stroke in this patient cohort with increased age and co-morbidities is elevated and anticoagulation is commonly indicated if AF is documented. Our results thus emphasize the importance of searching for AF in patients with chronic constriction. Major limitation of our study is retrospective nature of registry data. Reliable diagnosis of constrictive pericarditis and distinction from restrictive cardiomyopathy requires either surgical confirmation or detailed echocardiographic examination [8] commonly combined with cardiac catheterization [9]. As we collected data from all hospitals performing cardiovascular surgery and cardiac catheterizations in Finland, we most likely recognized all patients with clinical chronic constrictive pericarditis nationwide allowing reliable calculations at the population level. In conclusion, the standardized incidence of chronic constrictive pericarditis in general adult population is 3.4 per 1,000,000 personyears and men are at 2.3-fold risk of chronic constriction compared to women. Atrial fibrillation is common among patients with chronic constrictive pericarditis. Increasing age and renal insufficiency are associated with poor long-term survival in chronic constriction. Conflict of interest The authors report no relationships that could be construed as a conflict of interest.
Fig. 1. Frequency and age-distribution of chronic constrictive pericarditis (A), age-specific incidence of chronic constrictive pericarditis in general population (B), and Kaplan–Meier survival plot after initial admissions with chronic constrictive pericarditis (C). Error bars/ dashed lines represent 95% confidence intervals.
Pericardial constriction was the cause of death in 31.6% of cases, while myocardial infarction caused 15.8%, and congestive heart failure 10.5% of deaths. Cancer caused 15.8% of deaths and stroke 10.5%. One patient (5.3%) died of septicemia, one of renal insufficiency, and one of respiratory insufficiency. This nationwide study is, to our knowledge, the first contemporary description of chronic constrictive pericarditis at the population level. In agreement with the previous studies [3,4], we found 63% of patients to be male, and men had a 2.3 times higher risk for chronic constrictive
Funding Study was funded by the Clinical Research Foundation of Turku University Hospital. References [1] Maisch B, Seferovic PM, Ristic AD, et al. Guidelines on the diagnosis and management of pericardial diseases executive summary: the Task force on the diagnosis and management of pericardial diseases of the European society of cardiology. Eur Heart J 2004;25:587–610. [2] Clare GC, Troughton RW. Management of constrictive pericarditis in the 21st century. Curr Treat Options Cardiovasc Med 2007;9:436–42. [3] Oreto L, Mayer A, Todaro MC, et al. Contemporary clinical spectrum of constrictive pericarditis: a 10-year experience. Int J Cardiol 2013;163:339–41. [4] Bertog SC, Thambidorai SK, Parakh K, et al. Constrictive pericarditis: etiology and cause-specific survival after pericardiectomy. J Am Coll Cardiol 2004;43:1445–52.
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V. Kytö et al. / International Journal of Cardiology 176 (2014) 1158–1160
[5] Fairweather D, Cooper Jr LT, Blauwet LA. Sex and gender differences in myocarditis and dilated cardiomyopathy. Curr Probl Cardiol 2013;38:7–46. [6] Rezaian GR, Poor-Moghaddas M, Kojuri J, Rezaian S, Liaghat L, Zare N. Atrial fibrillation in patients with constrictive pericarditis: the significance of pericardial calcification. Ann Noninvasive Electrocardiol 2009;14:258–61. [7] Ling LH, Oh JK, Schaff HV, et al. Constrictive pericarditis in the modern era: evolving clinical spectrum and impact on outcome after pericardiectomy. Circulation 1999; 100:1380–6.
[8] Welch TD, Ling LH, Espinosa RE, et al. Echocardiographic diagnosis of constrictive pericarditis: Mayo Clinic criteria. Circ Cardiovasc Imaging 2014;7:526–34. [9] 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.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Chronic constrictive pericarditis in general adult population Ville Kytö a,d,⁎, Jussi Sipilä b,e, Päivi Rautava c,f a
Heart Center, Turku University Hospital, Turku, Finland Clinical Neurosciences, Neurology, Turku University Hospital, Turku, Finland c Clinical Research Center, Turku University Hospital, Turku, Finland d PET Center, University of Turku, Turku, Finland e Neurology, University of Turku, Turku, Finland f Public Health, University of Turku, Turku, Finland b
a r t i c l e
i n f o
Article history: Received 18 July 2014 Accepted 27 July 2014 Available online 4 August 2014 Keywords: Pericardial disease Pericarditis Constriction
Pericarditis is commonly an acute self-limiting virus triggered disease with good prognosis but when persistent it may lead to rigid and constricted pericardial sac resulting to constriction [1]. Etiology of constriction is mainly tuberculosis in Africa and developing countries, but acute pericarditis, post-surgical constriction, neoplasms, and other systemic diseases are main contemporary causes in the western countries [2]. Although a number of patient series of constriction have been published, there are however no studies on all-comer chronic constrictive pericarditis patients at population level. We studied occurrence, characteristics, and long-term outcome of chronic constrictive pericarditis in general adult population. All patients aged ≥18 years admitted to hospital between May 1st 2000 and October 31st 2009 with chronic constrictive pericarditis were identified from 29 hospitals by using the Finnish Hospital Discharge Register. Patients were followed for potential in-hospital mortality until the end of study period (median follow-up among survivors was 4.8 years, range 0.2–9.5 years). Primary discharge diagnosis of the last admissions ending in death was considered as the cause of death. Incidence was calculated using age- and sex-matched population data from the study period (38,402,024 person-years) obtained from Statistics Finland. The study was conducted according to the National Institute for Health and Welfare permission (THL/1576/5.05.00/2010).
⁎ Corresponding author at: Heart Center, Turku University Hospital, POB 52, FI-20521 Turku, Finland. Fax: +358 23137206. E-mail address: ville.kyto@utu.fi (V. Kytö).
http://dx.doi.org/10.1016/j.ijcard.2014.07.257 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Frequency and incidence were analyzed using Poisson regression models. In-hospital mortality was studied using exact Cox-regression model. Multivariate mortality model included patient characteristics associated with mortality at the p level b0.05 in univariate analysis. Total incidence rates were adjusted directly with the European standard population 2013. The SAS system version 9.3 (SAS Institute Inc., Cary, NC, USA) was used for statistical analyses. The study period included 713 hospital admissions occurring to 123 patients with constrictive pericarditis. Majority of patients were male (63.4%; CI 50.1–79.1% vs. 36.6%; CI 26.7–49.0%) with age-adjusted likelihood ratio of 1.73 (CI 1.20–2.50, p = 0.003) for male sex. Although constrictive pericarditis occurred in all age groups, 80.5% of patients were aged 50– 79 years (Fig. 1). Male patients were significantly younger than their counterparts (mean 61.2± 12.4 vs. 68.1 ±13.8 years, pb 0.0001). Incidencewas low(5.85[CI0.30–1.02]/1,000,000) in populationaged20–49,butincreased progressively from 50 to 79 years (Fig. 1). Standardized incidence was 3.44 (CI 2.88–4.08)/1,000,000 overall, 4.47 (CI 3.56–5.54) in men, and 2.42 (CI 1.79–3.21) in women. Men had an age-adjusted relative risk of 2.28 (CI 1.57–3.31; p b 0.0001) for constrictive pericarditis compared to their counterparts in general population. Atrial fibrillation (AF), congestive heart failure, and coronary artery disease were common in patients with constrictive pericarditis (Table 1). Atrial fibrillation was present in 39.8% of patients. In addition, 9.5% of patients in sinus rhythm developed AF during follow-up. Of potential etiologies, rheumatoid arthritis was present in 5.7%, malignancy in 4.1%, and tuberculosis in 0.8% of patients (Table 1). Majority (71.4%) of patients with rheumatoid arthritis had seropositive disease. Of patients with cancer, two (40%) had lung cancer, one (20%) melanoma, one gastric cancer and one chronic lymphocytic leukemia. Cardiac surgery had been performed to 4.9% of patients and 0.8% had previous rheumatic fever. None of the patients had diagnosed HIV, amyloidosis, carcinoid syndrome, or systemic connective tissue disease. Mortality rate during the follow-up period was 15.4% (CI 11.4– 29.7%) with median survival time of 112 days (Fig. 1) and twelvemonth survival of 88.6%. Factors associated with mortality in univariate analysis were age (HR 1.62; CI 1.04–2.52; p = 0.035 per 10-year increase) and renal insufficiency (HR 10.30, CI 1.44–74.80, p = 0.020). Potential etiologies or sex were not associated with death. In multivariate Cox analysis, renal insufficiency was an independent predictor of mortality (HR 7.76, CI 1.08–55.61, p = 0.04), while age had a borderline association with mortality (HR 1.58, CI 0.99–2.53; p = 0.055).
V. Kytö et al. / International Journal of Cardiology 176 (2014) 1158–1160
1159
Table 1 Co-morbidities and potential etiologies of constrictive pericarditis. Co-morbidity
N (total 123)
% (95% CI)
Atrial fibrillation Congestive heart failure Coronary artery disease Hypertension Diabetes Rheumatoid arthritis Previous cardiac surgery Malignancy Chronic pulmonary disease Hepatic disease/insufficiency Renal insufficiency Tuberculosis Previous rheumatic fever
49 39 33 17 10 7 6 5 5 5 2 1 1
39.8 (36.2–64.8) 31.7 (27.7–53.3) 26.8 (22.7–46.3) 13.8 (9.9–27.2) 8.1 (4.8–18.4) 5.7 (2.8–14.4) 4.9 (2.2–13.1) 4.1 (1.6–11.7) 4.1 (1.6–11.7) 4.1 (1.6–11.7) 1.6 (0.2–7.2) 0.8 (0.03–5.6) 0.8 (0.03–5.6)
pericarditis in general population. Reasons of sex predisposition are unclear, but experimental viral studies of myocardial inflammation have highlighted some potential mechanisms [5]. Sex hormones affect the risk for cardiac inflammation as progesterone and testosterone aggravate cardiac inflammation while estrogen has inhibitory effects [5]. Chronic constriction leads to increased atrial pressures and left atrial dilatation increasing the risk of AF [6]. We found the burden of AF to be significantly higher than the previously reported [3,6,7], as 40% of patients had AF at the baseline, and 10% of patients in sinus rhythm at baseline developed AF during follow-up. The risk of stroke in this patient cohort with increased age and co-morbidities is elevated and anticoagulation is commonly indicated if AF is documented. Our results thus emphasize the importance of searching for AF in patients with chronic constriction. Major limitation of our study is retrospective nature of registry data. Reliable diagnosis of constrictive pericarditis and distinction from restrictive cardiomyopathy requires either surgical confirmation or detailed echocardiographic examination [8] commonly combined with cardiac catheterization [9]. As we collected data from all hospitals performing cardiovascular surgery and cardiac catheterizations in Finland, we most likely recognized all patients with clinical chronic constrictive pericarditis nationwide allowing reliable calculations at the population level. In conclusion, the standardized incidence of chronic constrictive pericarditis in general adult population is 3.4 per 1,000,000 personyears and men are at 2.3-fold risk of chronic constriction compared to women. Atrial fibrillation is common among patients with chronic constrictive pericarditis. Increasing age and renal insufficiency are associated with poor long-term survival in chronic constriction. Conflict of interest The authors report no relationships that could be construed as a conflict of interest.
Fig. 1. Frequency and age-distribution of chronic constrictive pericarditis (A), age-specific incidence of chronic constrictive pericarditis in general population (B), and Kaplan–Meier survival plot after initial admissions with chronic constrictive pericarditis (C). Error bars/ dashed lines represent 95% confidence intervals.
Pericardial constriction was the cause of death in 31.6% of cases, while myocardial infarction caused 15.8%, and congestive heart failure 10.5% of deaths. Cancer caused 15.8% of deaths and stroke 10.5%. One patient (5.3%) died of septicemia, one of renal insufficiency, and one of respiratory insufficiency. This nationwide study is, to our knowledge, the first contemporary description of chronic constrictive pericarditis at the population level. In agreement with the previous studies [3,4], we found 63% of patients to be male, and men had a 2.3 times higher risk for chronic constrictive
Funding Study was funded by the Clinical Research Foundation of Turku University Hospital. References [1] Maisch B, Seferovic PM, Ristic AD, et al. Guidelines on the diagnosis and management of pericardial diseases executive summary: the Task force on the diagnosis and management of pericardial diseases of the European society of cardiology. Eur Heart J 2004;25:587–610. [2] Clare GC, Troughton RW. Management of constrictive pericarditis in the 21st century. Curr Treat Options Cardiovasc Med 2007;9:436–42. [3] Oreto L, Mayer A, Todaro MC, et al. Contemporary clinical spectrum of constrictive pericarditis: a 10-year experience. Int J Cardiol 2013;163:339–41. [4] Bertog SC, Thambidorai SK, Parakh K, et al. Constrictive pericarditis: etiology and cause-specific survival after pericardiectomy. J Am Coll Cardiol 2004;43:1445–52.
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V. Kytö et al. / International Journal of Cardiology 176 (2014) 1158–1160
[5] Fairweather D, Cooper Jr LT, Blauwet LA. Sex and gender differences in myocarditis and dilated cardiomyopathy. Curr Probl Cardiol 2013;38:7–46. [6] Rezaian GR, Poor-Moghaddas M, Kojuri J, Rezaian S, Liaghat L, Zare N. Atrial fibrillation in patients with constrictive pericarditis: the significance of pericardial calcification. Ann Noninvasive Electrocardiol 2009;14:258–61. [7] Ling LH, Oh JK, Schaff HV, et al. Constrictive pericarditis in the modern era: evolving clinical spectrum and impact on outcome after pericardiectomy. Circulation 1999; 100:1380–6.
[8] Welch TD, Ling LH, Espinosa RE, et al. Echocardiographic diagnosis of constrictive pericarditis: Mayo Clinic criteria. Circ Cardiovasc Imaging 2014;7:526–34. [9] 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.
