Analysis of risk factors for early mortality and multiorgan failure after pericardiectomy for constrictive pericarditis

Background:. The operative mortality of pericardiectomy is still high. This prospective study was to determine the risk factors for early mortality and multiorgan failure. Methods: We prospectively observe patients undergoing pericardiectomy from January 2009 to June 2020 at our hospital. Radical pericardiectomy was performed via sternotomy. Histopathologic studies of pericardum tissue from every patient was done. All survivors were monitored to the end date of the study. Results: 92 consecutive underdoing pericardiectomy for constrictive pericarditis were included in the study. Postoperatively ,CVP decreased signi�cantly, and LVED and LVEF improved signi�cantly. The overall mortality rate was 5.4%. The common postoperative complications inclued acute renal injury (cid:0)27.2%(cid:0), low cardiac output syndrome (10.9% ), and multiorgan failure (8.7%). Analysis of risk factor showed that D2 (�uid balance of the second day following operation) was associated with decreased early mortality and decreased multiorgan failure. In this series from Guagxi, China, characteristic histopathologic features of tuberculosis(cid:0)60/92,65.2%(cid:0) of pericardium were the most common histopathologic �ndings, and 32 patients (32/92,34.8%) had the histopathologic �ndings of chronic nonspeci�c in�ammatory changes. The functional status of the patients improved after pericardiectomy, 6 months postoperatively 85 survivors were in class I (85/87, 97.7%) and 2 in class II (2/87, 2.3%) . Conclusions: Our results show that pericardiectomy is an effective procedure in the treatment of constrictive pericarditis Early surgical intervention is advocated. Improvement of surgical technique and intraoperative and perioperative management can decrease mortality and morbidity.


Introduction
Constrictive pericarditis is a progressive and disabling disease and arises as a result of the brous thickening and calci cation of the pericardium due to chronic in ammatory changes from various injuries that impairs diastolic lling, reduces cardiac output, and ultimately leads to left and right heart failure.Patients with constrictive pericarditis undergo pericardiectomy with symptomatic improvement in over 90% of them after the procedure.[1][2][3] While the operative mortality risk of pericardiectomy is still high and ranges between 5% and 20%.[4,5] We hypothesized that improvement in the perioperative management and operative skills can decrease the operative mortality risk of pericardiectomy.This prospective study was conducted to determine the risk factors for early mortality and multiorgan failure (MOF) and to decrease the operative mortality risk of pericardiectomy.

Patients
We prospectively observe patients who underwent pericardiectomy for constrictive pericarditis from January 2009 to June 2020 at our hospital.
The diagnosis of constrictive pericarditis was con rmed by clinical presentation, echocardiographic study, chest computed tomographic (CT) scan and cardiac catheterization, as needed.(Figure 1, Figure 2) [6-9] 1.2 Surgical Technique Radical pericardiectomy was performed via sternotomy between the two phrenic nerves and from the great vessels to the basal aspect of the heart.In cases of high risk of coronary artery or myocardial damage, or severe bleeding, the pericardium over the right atrium or superior and inferior venae cavae was left intact.The primary intention was pericardiectomy without Cardiopulmonary bypass (CPB).
Perioperative death was de ned as death within 30 days of the operation or during the same hospital admission.
AKI was de ned according to the Acute Kidney Injury Network (AKIN) classi cation, using serum creatinine and urine output as criteria for the evaluation of renal function.

Histopathologic studies
Histopathologic studies of pericardum tissue from every patient was done.The diagnosis of tuberculosis was con rmed on the basis of clinical ndings and histopathologic features, including the presence of typical granuloma and caseous necrosis, acid-fast bacilli in Ziel-Nelson tissue staining, and bacteriologic studies using the polymerase chain reaction (PCR) test on the pericardial uid or tissue for evidence of mycobacterium tuberculosis.

Follow-up
All survivors discharged from hospital were monitored to the end date of the study.All patients at the outpatient department were examined with electrocardiogram, X-ray chest lm and echocardiogram, once every 3 to 6 months.At the last follow-up, the patients were contacted by telephone or micromassage or interviewed directly at the outpatient department.
The experiment protocol for involving humans was in accordance to national guidelines and was approved by the Medical Ethics Committee of The People's Hospital of Guangxi Zhuang Autonomous Region and The Medical Ethics Committee of The People's Hospital of Guangxi Zhuang Autonomous Region gave the authors approval to waive the need for patient consent for publishing data in the study about the patients.

Statistical analysis
Continuous variables are reported as means±SE.Survival rates were estimated using the Kaplan-Meier method.The chi-square test, the Kruskal-Walls test or the Wilcoxon rank-sum test , as appropriate, to be used to evaluate relationships between the preoperative variables, and selected intraoperative and postoperative variables.The relationships with perioperative risk factors were assessed by means of contingency table methods and logistic regression analysis.To explore the simultaneous effects of perioperative characteristics on early death, variables that were signi cant at the 0.1 level in univariate analysis were included in a multivariate logistic regression model.P values less than 0.05 were considered to be statistically signi cant.All analyses were performed using IBM SPSS version 24.0 software (IBM SPSS Inc., USA).
Cardiopulmonary bypass was performed in 8 patients (8/92,8.7%)with concomitant valve replacement.Only 2 patients underwent cardiac catheterization.Univariate analysis of potential risk factor for early mortality showed that Weight after diuresis was associated with decreased early mortality (OR=0.852,P=0.020).
Both univariate and multivariate analyses of risk factor for early mortality showed that D2 ( uid balance of the second day following operation) was a independent predictor of decreased early mortality.( Table 5.) Both univariate and multivariate analyses of risk factor for early mortality showed that D1 ( uid balance of the rst day following operation) was a independent predictor of increased early mortality.( Table 5.)

Analysis of risk factors for multiorgan failure
Univariate analysis of potential risk factor for multiorgan failure showed that postoperative chest drainage were associated with increased multiorgan failure (OR=1.001,P=0.042).
Both univariate and multivariate analyses of risk factor for multiorgan failure showed that D2 ( uid balance of the second day following operation) was a independent predictor of decreased multiorgan failure.D0 uid balance= uid balance on operation day; D1 uid balance= uid balance of the rst day following operation; D2 uid balance= uid balance of the second day following operation.

Follow-up results
All the 87 survivors discharged from hospital were monitored to the end date of the study and the followup was 100% completed (n=87).The mean duration of follow-up was 52.4±4.5 months (range, 2 to 138), no late death and reoperation occurred.Latest follow-up data showed that 85 survivors were in NYHA class I (85/87, 97.7%) and 2 in class II (2/87, 2.3%) .

Discussion
Constrictive pericarditis is de ned as the chronic brous thickening of the wall of the pericardial sac, which results in abnormal diastolic lling.Surgical pericardiectomy is extremely effective and possibly restorative for the heart failure, while it is particularly challenging because of the increased risk of right heart failure.[10][11][12][13][14] Surgical removal of the pericardium is associated with a operative mortality rate of 5% to 20% in various large series.Myocardial atrophy after prolonged constriction, residual constriction, or a concomitant myocardial process can lead to prolonged cardiac failure despite successful pericardiectomy.[15][16][17][18] 3.1 Improvement of surgical technique In order to avoid pulmonary edeama and the heart is damaged due to excessive expansion because a large amount of tissue uid ows back the heart and the lung, the pericardium was decorticated in the following order: left ventricular out ow tract -apex of heart -right ventricular out ow tract -right ventricle -superior and inferior vena cava entrance -pericardium diaphragm surface.
If the pericardium calci cation is serious and closely adheres to the myocardium, it is di cult to completely peel off the pericardium.The local "#'"shaped incision is used to release the pericardium.[19][20][21] 3.2 Mortality and cardiac output syndrome Low cardiac output syndrome was the most common cause of death during the early postoperative phase in the present study.This low cardiac output state after pericardiectomy might have been due to incomplete pericardiectomy.Nonetheless, postoperative transient interstitial edema, could have had an impotant effect.Correct and effective perioperative management is of great signi cance to reduce the operative mortality.After pericardiectomy, the heart is in a high volume load state in a short period of time.At this time, usage of large amount of diuretics becomes feasible and necessary, which is also one of the key points for further improvement of cardiac function after operation.[22][23][24] The following measures are important to decrease the operative mortality risk of pericardiectomy.(1) strengthen nutrition before operation to improve general condition, intermittently input of plasma or albumin to increase colloidal osmotic pressure, and Aggressive diuresis is completed to reduce tissue edema to reduce the amount of blood returning the heart postoperatively.(2) During and after the operation, carry out continuous invasive monitoring of arterial and venous pressure.The amount of crystal input is strictly controlled.Fresh frozen plasma and albumin are properly imported.Aggressive diuresis is performed in order to avoid further aggravating the burden on the heart and causing heart failure.Regular anti tuberculosis treatment is given to patients with tuberculosis.(3) After pericardial stripping off and release of superior and inferior vena cava, active diuresis, cardiotonic drugs and vasoactive drugs should be applied.The application time of vasoactive drugs should be appropriately prolonged and gradually reduced.(4) After the operation, the infusion volume and speed should be strictly controlled, and the negative balance should be maintained.Routinely use vasoactive drugs, such as dopamine, dobutamine, nitroprusside, etc.; rationally use diuretics.Due to the long-term compression of the thickened pericardium and myocardial ischemia, the heart denaturates and atrophies, and the heart has poor adaptability to the changes of hemodynamics.After the heart is released, a large amount of blood ows back and the load of the heart increases, which leads to the occurrence of heart failure or malignant arrhythmia, and often leads to cardiac arrest.The postoperative low-output state gradually improved in most of patients.[25,26] Pathological Discussion In this series from Guagxi, China, characteristic histopathologic features of tuberculosis of pericardium 60/92,65.2%were the most common histopathologic ndings, following by the chronic nonspeci c in ammatory changes (32/92,34.8%)(Table 6).
Constrictive pericarditis exhibits a heterogeneous pattern and arises from different causes, depending on the geographic area from which it is reported.38% to 83% of the cases of constrictive pericarditis are still caused by tuberculosis in developing countries.Table 6.shows the prevalence of causal factors for constrictive pericarditis in treatment centers in the United States, Spain, Iran and China.[27,28]

Conclusions
Our results show that pericardiectomy is an effective procedure in the treatment of constrictive pericarditis for it yields excellent functional outcomes.Early surgical intervention is advocated, as constrictive pericarditis is a progressive disease.Improvement of surgical technique and intraoperative and perioperative management can decrease mortality and morbidity.

Figures
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Table 5 .
Analysis of risk factors for early mortality and multiorgan failure

Table 6 .
Prevalence of Causal Factors for Constrictive Pericarditis in Treatment Centers in the United States, Spain, Iran and China