A 67-year-old male patient received a coronary artery bypass graft. Less than 2 months afterward, he presented with recurrent exacerbations of congestive heart failure. His response to a standard treatment regimen for heart failure was partly successful, but a few days after discharge he was readmitted for worsening dyspnea and edema. Doppler echocardiography suggested the hemodynamics of constrictive pericarditis. Magnetic resonance imaging showed thickened pericardium with exudates in the pericardial space. Cardiac catheterization confirmed the diagnosis, showing equalization of diastolic pressures of the left and right ventricles. The patient underwent subtotal pericardiectomy with resolution of the pericardial disease, but he died from respiratory insufficiency.

In this MMed thesis I have reviewed retrospectively the pericardial aspirations performed between 1 July 1987 and 12th October 1989 at Groote Schuur Hospital, Cape Town. Documenting the reasons for aspiration, the complications of pericardiocentesis, and how cytologic, bacteriologic and biochemical examination of the aspirate influenced the clinicians' management of the 52 patients reviewed. The relatively low mortality of less than 2% is noted, in a procedure carried out for the relief of cardiac tamponade in 57% of the patients. A significant relationship between an ADA level higher than 51 international units per litre and a positive culture of mycobacterium tuberculosis from pericardial aspiration is demonstrated. The relatively low successful culture of mycobacterium tuberculosis (32% of the 29 patients clinically assessed as having tuberculous pericarditis) is noted, and recommendations to improve the yield from culture are made.

Constrictive pericarditis (CP) is an uncommon disease with multiple causes and discrepant clinical outcome. Till date, there is a scarcity of publications, clearly defining the risk factors of poor outcomes after surgery for CP. Therefore, we retrospectively analysed the results of the surgical treatment for CP at our institution to define the risk factors of poor outcomes. A total of 97 patients (65 male, 67%) undergoing surgery for CP at our institution from 1995 to 2012 were included in this study. CP was diagnosed either preoperatively by cardiac catheterization or at surgery. The mean age was 60±12.5 years and the primary etiology was idiopathic in more than halt the cases, followed by prior cardiac surgery, post-irradiation, and miscellaneous. Preoperative and intraoperative risk factors for 30-day and late mortality were analyzed using stepwise multivariate logistic and Cox regression analysis respectively. Long-term survival was determined by the Kaplan-Meier curve. Mean follow-up was 2.9±3.8 years (range: 0.1-14 years). All patients received either radical (53 patients, 55.2%) or partial (44 patients, 44.8%) pericardiectomy. Concomitant procedures were performed in 38 (39,2%) patients. Overall 30-day, 1-year and 5-year survival were 66.8 %, 58.1% and 52.6% respectively, without significant difference according to the underlying etiology. Univariate analysis showed that preoperative renal dysfunction, liver failure, respiratory insufficiency, emergency surgery and longer operating times were associated with significantly higher 30-day mortality. Multivariate analysis revealed patients with concomitant coronary artery disease to be at higher risk of poor immediate survival, whereas a higher glomerular filtration rate GFR (ml/min/1,73m2) was protective for early mortality. Long-term mortality was independently predicted by the presence of a coronary artery disease, a COPD (chronic obstructive pulmonary disease) and higher absolute creatinine value. To conclude, surgery for constrictive pericarditis is associated with a relatively poor prognosis. Reduced left ventricular ejection fraction and right ventricular dilatation were independent predictors for early mortality, while coronary artery disease, chronic obstructive pulmonary disease, and renal insufficiency were risk factors for late mortality. Thus, indication for surgery needs to be determined on an individual basis and should be justified by an otherwise worse natural prognosis.:1 CONTENTS 1 CONTENTS I 2 ABBREVIATIONS III 3 BIBLIOGRAPHIC DESCRIPTION 1 3.1 REVIEW 1 4 INTRODUCTION 3 4.1 CHRONIC CONSTRICTIVE PERICARDITIS 3 4.2 HISTORY 6 4.3 DEFINITION 8 4.3.1 ACUTE PERICARDITIS 8 4.3.2 RECURRENT PERICARDITIS 9 4.3.3 PERICARDIAL EFFUSION, PERICARDIAL TAMPONADE, EFFUSIVE-CONSTRICTIVE PERICARDITIS 10 4.3.4 CHRONIC PERICARDITIS 12 4.3.5 CHRONIC CONSTRICTIVE PERICARDITIS 14 4.3.6 CLINICAL PRESENTATION 16 4.3.7 DIAGNOSTIC APPROACH 18 4.3.8 TREATMENT OPTIONS 23 4.3.9 PERICARDIECTOMY 24 5 AIM OF THE STUDY 29 6 MATERIAL AND METHODS 30 6.1 DATA COLLECTION 30 6.2 DIAGNOSIS OF CONSTRICTIVE PERICARDITIS 31 6.3 OPERATIVE PROCEDURES 31 6.4 OPERATIVE TECHNIQUE 32 6.5 POSTOPERATIVE COURSE 33 6.6 INCLUSION CRITERIA 34 6.7 EXCLUSION CRITERIA 34 6.8 FOLLOW UP 34 6.9 STATISTICS 35 6.10 STATISTICAL MODEL 37 7 RESULTS 39 7.1 PREOPERATIVE CHARACTERISTICS 39 7.2 ETIOLOGY 42 7.2.1 INDEPENDENT PREDICTORS FOR ALL-CAUSE EARLY MORTALITY 44 7.2.2 INDEPENDENT PREDICTORS FOR ALL-CAUSE LONG-TERM MORTALITY 44 7.3 MORTALITY 46 7.3.1 ALL-CAUSE MORTALITY 46 7.3.2 SURVIVAL ACCORDING TO ETIOLOGY 47 7.3.3 LATE SURVIVAL WITHOUT PERIOPERATIVE DEATHS 48 7.3.4 ISOLATED PERICARDIECTOMY VS. CONCOMITANT SURGERY 49 7.3.5 POSTOPERATIVE OUTCOMES: 50 7.3.6 RECEIVER OPERATING CHARACTERISTIC (ROC) CURVE 51 8 DISCUSSION 54 8.1.1 PERSONAL THOUGHTS AND FUTURE DIRECTIONS 58 9 LIMITATIONS 61 10 CONCLUSION 62 11 SUMMARY 63 12 REFERENCES 65 13 ATTACHMENTS 70 13.1 DIAGNOSTIC APPROACH IN CONSTRICTIVE PERICARDITIS 70 13.2 FOLLOW-UP QUESTIONNAIRE 72 14 NOTE OF THANKS 80 15 DANKSAGUNG 81 16 ERKLÄRUNG ÜBER DIE EIGENSTÄNDIGE ABFASSUNG DER ARBEIT 82 17 CURRICULUM VITAE 83

We are reporting an unusual case of cat-scratch disease in a young adolescent girl presenting with recurrent ascites. The illness started with nonspecific symptoms followed by ascites and an axillary lymph node enlargement. She had recurrent ascites for 18 months associated with constrictive pericarditis. Following pericardiectomy, she had a resolution of ascites and was back to her normal life. This is a first documented report of a constrictive pericarditis following cat scratch diseases in English literature.

Introdução: A pericardiectomia é o tratamento de escolha para pacientes com pericardite constritiva crônica sintomática, entretanto, o impacto do procedimento na capacidade cardiopulmonar e fisiologia cardiorrespiratória durante a vigília e sono é pouco estudado. Objetivo: Avaliar o impacto da cirurgia de pericardiectomia sobre a capacidade funcional de pacientes com pericardite constritiva crônica sintomática. Métodos: Trata-se de estudo observacional prospectivo com 25 pacientes consecutivos com diagnóstico de pericardite constritiva crônica submetidos à pericardiectomia. Foram realizados os seguintes procedimentos uma semana antes e seis meses após a pericardiectomia: avaliação clínica e antropométrica, avaliação da qualidade de vida e do sono, dosagem dos níveis séricos de BNP, ecocardiograma transtorácico, teste cardiopulmonar de esforço, polissonografia noturna completa. Resultados: A idade média foi 45 anos, com predomínio do sexo masculino (76%). A etiologia foi principalmente idiopática (76%), seguida por tuberculose (12%). O ecocardiograma revelou fração de ejeção do ventrículo esquerdo preservada e dilatação de veia cava inferior (92%) na maioria dos pacientes. Todos os pacientes foram submetidos à pericardiectomia de frênico a frênico via esternotomia mediana, sem circulação extracorpórea. Após a pericardiectomia, houve redução da: classe funcional III/IV (56% vs. 8%, p < 0,001), ascite (72% vs. 12%, p < 0,001) e edema de membros inferiores (88% vs. 24%, p < 0,001) em relação ao pré-operatório. O teste cardiopulmonar revelou melhora do VO2 pico (18,7 ± 5,6 vs. 25,2 ± 6,3 mL/kg/min, p < 0,001), limiar anaeróbico (13,1 ± 3 vs. 17,7 ± 5,5 mL/kg/min, p < 0,001) e velocidade na esteira rolante de 2,5 (2-2,5) para 3 (2,5-3,3) mph, p=0,001. Na análise multivariada, a idade foi o único preditor independente da variação de VO2 (r=-0,658, p=0,003). Os níveis séricos de BNP apresentaram redução significativa de 143 (83,5-209,5) pg/mL para 76 (40-117,5) pg/mL, p=0,011. A polissonografia noturna completa no pré-operatório demonstrou a presença de apneia do sono moderada/ grave (IAH >= 15 eventos/hora) em 13 pacientes, com predomínio de hipopneias. Não houve mudança significativa do índice de apneia-hipopneia após a pericardiectomia: IAH pré 15,6 (8,3-31,7) vs. IAH pós 14,6 (5,75-29,9), p=0,253; entretanto, houve melhora da qualidade do sono (Pittsburgh pré 7,8 ± 4,10 vs. Pittsburgh pós 4,7 ± 3,7, p < 0,001). O IAH apresentou correlação positiva com os níveis de BNP (r=0,418, p=0,037) e EuroSCORE (r=0,480, p=0,015) no pré-operatório. Conclusão: Pacientes com pericardite constritiva crônica sintomática apresentaram, seis meses após a cirurgia de pericardiectomia, melhora da capacidade cardiopulmonar, da classe funcional e da qualidade de vida. A apneia do sono se mostrou frequente e apresentou correlação com níveis séricos de BNP e EuroSCORE no pré-operatório. O índice de apneia-hipopneia não apresentou mudanças significativas após a pericardiectomia. A despeito disso, houve melhora da qualidade do sono / Introduction: Pericardiectomy is the treatment of choice for patients with symptomatic chronic constrictive pericarditis; however, the impact of the procedure on cardiopulmonary capacity and cardiorespiratory physiology during wakefulness and sleep has been poorly studied so far. Objective: To evaluate the impact of pericardiectomy surgery on functional capacity of patients with symptomatic chronic constrictive pericarditis. Methods: This is a prospective observational study with 25 consecutive patients diagnosed with chronic constrictive pericarditis submitted to pericardiectomy. The following procedures were performed one week before and six months after pericardiectomy: clinical and anthropometric evaluation, quality of life and sleep evaluation, serum BNP levels, transthoracic echocardiography, cardiopulmonary exercise test, complete nocturnal polysomnography. Results: The mean age was 45, with a predominance of males (76%). The etiology was mainly idiopathic (76%), followed by tuberculosis (12%). The echocardiogram revealed preserved left ventricular ejection fraction and inferior vena cava dilatation (92%) in most patients. All patients underwent phrenic to phrenic pericardiectomy via median sternotomy, without extracorporeal circulation. After pericardiectomy there was a reduction in: functional class III / IV (56% vs. 8%, p < 0.001), ascites (72% vs. 12%, p < 0.001) and lower limb edema (88% vs. 24%, p < 0.001) as compared to the preoperative period. The cardiopulmonary test revealed improvement in VO2 peak (18.7 ± 5.6 vs. 25.2 ± 6.3 mL/kg/min, p < 0.001), anaerobic threshold (13.1 ± 3 vs. 17.7 ± 5.5 mL/kg/min, p < 0.001) and velocity on the treadmill from 2.5 (2-2.5) to 3 (2.5-3.3) mph, p=0.001. In multivariate analysis, age was the only independent predictor of VO2 variation (r = -0.658, p = 0.003). Serum BNP levels showed a significant reduction from 143 (83.5-209.5) pg/mL to 76 (40-117.5) pg/mL, p=0.011. The complete nocturnal polysomnography in the preoperative period showed moderate / severe sleep apnea (AHI >= 15 events / hour) in 13 patients, predominantly hypopnea. There was no significant change in apnea-hypopnea index after pericardiectomy: AHI pre 15.6 (8.3-31.7) vs. AHI post 14.6 (5.75-29.9), p= 0.253; however, there was improvement in sleep quality (Pittsburgh pre 7.8 ± 4.10 vs. Pittsburgh post 4.7 ± 3.7, p < 0.001). AHI presented a positive correlation with BNP levels (r=0.418, p=0.037) and EuroSCORE (r=0.480; p=0.015) in the preoperative period. Conclusion: Patients with symptomatic chronic constrictive pericarditis showed improvement in cardiopulmonary capacity, functional class and quality of life six months after pericardiectomy. Sleep apnea was frequent and correlated with serum levels of BNP and EuroSCORE in the preoperative period. The apnea-hypopnea index did not show significant changes after pericardiectomy. Nevertheless, there was an improvement in sleep quality

Introdução: A pericardiectomia é o tratamento de escolha para pacientes com pericardite constritiva crônica sintomática, entretanto, o impacto do procedimento na capacidade cardiopulmonar e fisiologia cardiorrespiratória durante a vigília e sono é pouco estudado. Objetivo: Avaliar o impacto da cirurgia de pericardiectomia sobre a capacidade funcional de pacientes com pericardite constritiva crônica sintomática. Métodos: Trata-se de estudo observacional prospectivo com 25 pacientes consecutivos com diagnóstico de pericardite constritiva crônica submetidos à pericardiectomia. Foram realizados os seguintes procedimentos uma semana antes e seis meses após a pericardiectomia: avaliação clínica e antropométrica, avaliação da qualidade de vida e do sono, dosagem dos níveis séricos de BNP, ecocardiograma transtorácico, teste cardiopulmonar de esforço, polissonografia noturna completa. Resultados: A idade média foi 45 anos, com predomínio do sexo masculino (76%). A etiologia foi principalmente idiopática (76%), seguida por tuberculose (12%). O ecocardiograma revelou fração de ejeção do ventrículo esquerdo preservada e dilatação de veia cava inferior (92%) na maioria dos pacientes. Todos os pacientes foram submetidos à pericardiectomia de frênico a frênico via esternotomia mediana, sem circulação extracorpórea. Após a pericardiectomia, houve redução da: classe funcional III/IV (56% vs. 8%, p < 0,001), ascite (72% vs. 12%, p < 0,001) e edema de membros inferiores (88% vs. 24%, p < 0,001) em relação ao pré-operatório. O teste cardiopulmonar revelou melhora do VO2 pico (18,7 ± 5,6 vs. 25,2 ± 6,3 mL/kg/min, p < 0,001), limiar anaeróbico (13,1 ± 3 vs. 17,7 ± 5,5 mL/kg/min, p < 0,001) e velocidade na esteira rolante de 2,5 (2-2,5) para 3 (2,5-3,3) mph, p=0,001. Na análise multivariada, a idade foi o único preditor independente da variação de VO2 (r=-0,658, p=0,003). Os níveis séricos de BNP apresentaram redução significativa de 143 (83,5-209,5) pg/mL para 76 (40-117,5) pg/mL, p=0,011. A polissonografia noturna completa no pré-operatório demonstrou a presença de apneia do sono moderada/ grave (IAH >= 15 eventos/hora) em 13 pacientes, com predomínio de hipopneias. Não houve mudança significativa do índice de apneia-hipopneia após a pericardiectomia: IAH pré 15,6 (8,3-31,7) vs. IAH pós 14,6 (5,75-29,9), p=0,253; entretanto, houve melhora da qualidade do sono (Pittsburgh pré 7,8 ± 4,10 vs. Pittsburgh pós 4,7 ± 3,7, p < 0,001). O IAH apresentou correlação positiva com os níveis de BNP (r=0,418, p=0,037) e EuroSCORE (r=0,480, p=0,015) no pré-operatório. Conclusão: Pacientes com pericardite constritiva crônica sintomática apresentaram, seis meses após a cirurgia de pericardiectomia, melhora da capacidade cardiopulmonar, da classe funcional e da qualidade de vida. A apneia do sono se mostrou frequente e apresentou correlação com níveis séricos de BNP e EuroSCORE no pré-operatório. O índice de apneia-hipopneia não apresentou mudanças significativas após a pericardiectomia. A despeito disso, houve melhora da qualidade do sono / Introduction: Pericardiectomy is the treatment of choice for patients with symptomatic chronic constrictive pericarditis; however, the impact of the procedure on cardiopulmonary capacity and cardiorespiratory physiology during wakefulness and sleep has been poorly studied so far. Objective: To evaluate the impact of pericardiectomy surgery on functional capacity of patients with symptomatic chronic constrictive pericarditis. Methods: This is a prospective observational study with 25 consecutive patients diagnosed with chronic constrictive pericarditis submitted to pericardiectomy. The following procedures were performed one week before and six months after pericardiectomy: clinical and anthropometric evaluation, quality of life and sleep evaluation, serum BNP levels, transthoracic echocardiography, cardiopulmonary exercise test, complete nocturnal polysomnography. Results: The mean age was 45, with a predominance of males (76%). The etiology was mainly idiopathic (76%), followed by tuberculosis (12%). The echocardiogram revealed preserved left ventricular ejection fraction and inferior vena cava dilatation (92%) in most patients. All patients underwent phrenic to phrenic pericardiectomy via median sternotomy, without extracorporeal circulation. After pericardiectomy there was a reduction in: functional class III / IV (56% vs. 8%, p < 0.001), ascites (72% vs. 12%, p < 0.001) and lower limb edema (88% vs. 24%, p < 0.001) as compared to the preoperative period. The cardiopulmonary test revealed improvement in VO2 peak (18.7 ± 5.6 vs. 25.2 ± 6.3 mL/kg/min, p < 0.001), anaerobic threshold (13.1 ± 3 vs. 17.7 ± 5.5 mL/kg/min, p < 0.001) and velocity on the treadmill from 2.5 (2-2.5) to 3 (2.5-3.3) mph, p=0.001. In multivariate analysis, age was the only independent predictor of VO2 variation (r = -0.658, p = 0.003). Serum BNP levels showed a significant reduction from 143 (83.5-209.5) pg/mL to 76 (40-117.5) pg/mL, p=0.011. The complete nocturnal polysomnography in the preoperative period showed moderate / severe sleep apnea (AHI >= 15 events / hour) in 13 patients, predominantly hypopnea. There was no significant change in apnea-hypopnea index after pericardiectomy: AHI pre 15.6 (8.3-31.7) vs. AHI post 14.6 (5.75-29.9), p= 0.253; however, there was improvement in sleep quality (Pittsburgh pre 7.8 ± 4.10 vs. Pittsburgh post 4.7 ± 3.7, p < 0.001). AHI presented a positive correlation with BNP levels (r=0.418, p=0.037) and EuroSCORE (r=0.480; p=0.015) in the preoperative period. Conclusion: Patients with symptomatic chronic constrictive pericarditis showed improvement in cardiopulmonary capacity, functional class and quality of life six months after pericardiectomy. Sleep apnea was frequent and correlated with serum levels of BNP and EuroSCORE in the preoperative period. The apnea-hypopnea index did not show significant changes after pericardiectomy. Nevertheless, there was an improvement in sleep quality

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