Does tuberculosis affect surgical outcomes following pericardiectomy for chronic constrictive pericarditis? Twelve years’ experience from a tertiary care center in India

Abstract

Introduction and purpose

Tuberculosis (TB) is the commonest cause of chronic constrictive pericarditis (CCP) in India, unlike in the western countries. Pericardiectomy is the treatment of choice for CCP. Surgery in TB CCP is considerably more difficult than it is for other etiologies. The role of TB as an independent predictor for adverse surgical outcomes had not been properly evaluated in the Indian scenario. Hence, the aim of this study was to retrospectively analyze our results of surgery for CCP and the pre-operative factors that influenced post-operative outcomes.

Methods

The data of all adult patients who underwent pericardiectomy for CCP, between the years 2009 and 2020, maintained in a live database in our institute, were retrieved and analyzed.

Results

There were 124 patients in the study. The average age was 32 years. The male to female ratio was 3:1. TB was the commonest cause of CCP, identified in 64 (51.6%) patients. Complete anterior pericardiectomy (CAP) was possible in 122 (98.3%) patients. All the patients had significant drop in their central venous pressure (CVP) (10.25 ± 3.47 mmHg) after surgery. The operative time (p = 0.008), intra-operative blood loss (p = 0.02), intensive care unit (ICU) stay (p = 0.03), and hospital stay (p = 0.028) were significantly higher in the TB group. Apart from TB, the other pre-operative variables that predicted adverse outcomes were male sex, presence of pleural effusion or ascites, and advanced New York Heart Association (NYHA) class. There were 7 (5.6%) post-operative complications and 3 (2.4%) in-hospital deaths.

Conclusion

The high incidence of TB CCP makes a pericardiectomy in developing countries technically more challenging resulting in increased operative time, more blood loss, and prolonged ICU and hospital stay, but did not affect in-hospital mortality or morbidity.

Introduction

Chronic constrictive pericarditis (CCP) develops as a result of chronic inflammation of the pericardium, which leads to its thickening, fibrosis, and contraction. The elasticity of the pericardium and the volume of its cavity are lost in this process and this limits diastolic ventricular filling [1]. In the western literature, the most common causes of CCP are uremia, cardiac surgical procedures, irradiation, and neoplasia [2, 3]. In contrast, tuberculosis (TB) is the most common etiology for CCP in developing countries like India [4]. Pericardiectomy is the only established definitive treatment for CCP that alleviates symptoms and improves cardiac dynamics [5]. But this procedure carries with it significant morbidity and mortality [6], which are worse when TB is the etiology. Thus, our cohort of patients with TB as the commonest etiology is entirely different from what is described in western literature, and hence we endeavored to retrospectively analyze the details of our patients who underwent surgery for CCP with a special focus on the impact of TB in the presentation, management, and outcomes. A large single-center study from India had concluded that TB did not affect outcomes [4]. A pericardiectomy may be done through a median sternotomy or a thoracotomy, with or without the aid of cardiopulmonary bypass (CPB). Complete anterior pericardiectomy (CAP) which includes removal of pericardium from the innominate vein to the diaphragm and between the phrenic nerves is the recommended and commonly performed procedure [5].

Aims and objectives

The primary aim of the study was to determine the difference in surgical outcomes between TB and the non-TB subset of patients with CCP. The objectives included:

1. To study the etiological and risk factors associated with CCP.

2. To determine the pre-operative variables that influenced the outcomes after pericardiectomy.

Methodology

The live electronic database of case files of all adult patients who underwent surgery for CCP in our institution, between January 2009 and March 2020, was analyzed. This study was a retrospective observational study. The approval of the institutional review board was obtained (IRB min no: 14057 dated 30/06/2021). Written informed consent for study and publication was obtained from the patients prior to the surgery. The patients were divided into TB and non-TB subsets based on the post-operative histopathology or microbiology reports of the excised pericardium.

Inclusion criteria

1. Patients who underwent pericardiectomy for CCP, which was confirmed by echocardiography and computed tomogram (CT).

Exclusion criteria

1. Patients who underwent pericardiectomy for any non-constricting pericardial pathology like pyopericardium.

2. Patients below the age of 15 years.

Statistical analysis

All statistical analyses of various parameters were done using the Excel worksheet and SPSS version 21 software. All comparative analyses were done by the chi-square test for qualitative variables and Student’s t test for quantitative variables. A “p” value of less than 0.05 was considered significant. Univariate analysis was done to find out the factors that predicted adverse surgical outcomes. Multivariate analysis was done on all factors that were identified on univariate analysis to have predicted adverse outcomes with a “p” value less than 0.1. Multiple logistic regression models were used for this analysis.

Pre-operativeworkupand diagnosis

All patients with a diagnosis of CCP were advised surgery. Baseline blood tests, including liver function tests (LFT), were done. Diagnosis was made by echocardiography and was confirmed with a CT. Echocardiography features include ventricular septal motion abnormality (from ventricular interdependence), medial mitral annulus E velocity ≥ 9 cm/s, and hepatic vein expiratory diastolic reversal ratio ≥ 0.79, in addition to restrictive mitral inflow velocity (E/A ratio > 0.8) and plethoric inferior vena cava [7]. CT features included thickened pericardium (> 4 mm) with or without calcification, tubular and constricted ventricles, dilated atria, and reflux of dye into the inferior vena cava and hepatic veins (Fig. 1a–d). CT and echocardiography together helped to differentiate CCP from restrictive cardiomyopathy. Coronary angiogram was done in patients more than 40 years of age, those with suspected history of myocardial ischemia and in those who are at a high risk for ischemic heart disease. Most of our patients had been already medically optimized when they presented to us. If not, medical optimization with diuretics was initiated and continued until after surgery. Patients with serum albumin less than 3 g/dl were placed on a high protein diet and were infused intravenous albumin for 3 days prior to surgery. Anemic patients, with hemoglobin less than 9 g/dl, were transfused. Patients with active TB anywhere were operated upon only after the intensive phase of anti-tubercular therapy (ATT).

Fig. 1.

CT features of CCP, a) thickened pericardium (white arrow) with bilateral pleural effusion (black arrows), b) thickened and calcified pericardium (white arrow), c) tubular, constricted ventricles (red arrow) and dilated atria (white arrow) and d) dilated left atrium (red arrow) with dilated IVC and hepatic vein (white arrow)

Surgical details

All procedures were done through median sternotomy without the aid of CPB. External defibrillator paddles were routinely applied while positioning the patient for surgery. The right femoral vascular access area was exposed and kept ready, in case an emergency CPB was required. CAP was done in most of the patients except a few in whom completion was not possible due to severe disease process, for fear of causing major cardiac or coronary injury. The right ventricular outflow and inflow were always cleared to the maximum extent possible. Pericardium was dissected using blunt and sharp dissection. The sequence of pericardiectomy was as follows: First the pericardium over the root of the aorta was cleared, in case an emergency CPB was required. Following this, the right ventricular outflow tract was cleared and then the right ventricle, atrioventricular groove, right atrium, and the venae cava. This sequence was adopted so as to prevent sudden distension of the right ventricle, if the right ventricular inflow was cleared first. Subsequently, the pericardium was cleared over the left ventricle. The entire pericardium between the two phrenic nerves, down until the diaphragm, was removed. Any inadvertent injury to a cardiac chamber was sutured with pledgetted polypropylene sutures. If the pericardium was found to be too adherent, multiple cruciate incisions were made on its surface to help the underlying heart to expand between the incisions. CPB was resorted to if a repair of any major cardiac injury mandated it. Both the pleurae were widely opened and three intercostal drainage tubes (ICD) were placed, one in either pleural cavity and one in the mediastinum. The chest was closed in the conventional manner. The central venous pressure (CVP) was monitored continuously throughout the procedure. The excised pericardium was sent for microbiological and histopathological studies. No viral studies were done.

Post-operative management

Patients were started on inotropes intra-operatively to optimize cardiac function. Adrenaline (0.02 to 0.2 mcg/kg/min) was used routinely in our center. Dopamine (3.5 to 5 mcg/kg/min) was used in patients with low urine output after blood pressure and preload optimization. In recent years, milrinone (0.375 to 0.75 mcg/kg/min) has been used for its ability to reduce the right ventricular afterload in addition to being an inotrope. Nor-adrenaline (0.02 to 0.2 mcg/kg/min) was used for afterload optimization in patients who were on milrinone. Diuretics and digoxin were started in the immediate post-operative period. All patients were electively ventilated for at least 12 h after surgery. They were extubated if their ventilatory and hemodynamic performances were satisfactory. The patients were monitored in the intensive care unit (ICU) for the first 72 h post-operatively, before being transferred to the ward. The ICD were removed once the drainage was less than 100 ml in 24 h. Post-operative pain control was achieved by oral or parenteral analgesics and non-steroidal anti-inflammatory agents. Patients were followed up after 3 months, 1 year, and then at yearly intervals. The patients with newly diagnosed TB post-operatively were prescribed weight-based ATT for 6 months and those who were already on ATT went on to complete the 6-month course. On follow-up, the ATT was adjusted as per the culture reports and the toxicity of drugs, if any.

Definitions

Pre-operative CVP was defined as the CVP reading obtained through internal jugular line inserted just before surgery. Operative time was defined as the time taken from the starting of surgical skin incision to complete closure of the same. Intra-operative blood loss was calculated by the anesthetists by taking into account the number of blood-soaked gauzes and sponges, and the amount of blood collected in the suction reservoirs. Post-operative CVP was defined as the CVP reading obtained after sternal closure. ICU stay was defined in hours as the time from the patients’ reception in ICU to the time when the patient was shifted to the ward. Hospital stay in days was defined as the time from the day of surgery to the day of discharge. ICU stay of more than 72 h and hospital stay of more than 10 days were considered as prolonged [8]. Re-admission due to congestive cardiac failure (CCF) within 30 days of discharge was considered a post-operative complication. Prolonged ventilation was defined as patients requiring ventilation for more than 24 h [9]. Adverse surgical outcome was defined as any post-operative complication, in-hospital mortality, prolonged ICU stay, and prolonged hospital stay.

Results

Patient demographics

A total of 124 adult patients underwent pericardiectomy for CCP in our institution between 2009 and 2020. The average age was 32 ± 15.4 years (range 15–73) with 89 (72%) of them below the age of 40. The male to female ratio was 3:1. The common presenting complaints were dyspnea in 102 (82.3%), chest pain in 56 (45%), and fever in 44 (35.5%) patients. Ninety-one (73.3%) presented with New York Heart Association (NYHA) class II symptoms. The duration of symptoms was significantly more in the non-TB subset (Table 1). At presentation, 101 (81.5%) patients had pedal edema, 77 (62%) had raised jugular venous pressure (JVP), and 69 (55.6%) patients had ascites.

Table 1.

Comparison of patient characteristics between TB and non-TB groups

	TB (n = 64)	Non-TB (n = 60)	P value
Age in years (mean ± SD)	31.1 ± 15.28	33.3 ± 15.6	0.42
Sex ratio (M:F)	3.3:1	3:1	1.0
NYHA class II symptoms	47 (73.4%)	44 (73.3%)	1.0
NYHA class III symptoms	16 (25%)	14 (23.3%)	0.83
NYHA class IV symptoms	1 (1.5%)	2 (3.3%)	0.61
Duration of symptoms in months (mean ± SD)	12 ± 3.4	23 ± 3.5	0.001*
Pedal edema	54 (84.4%)	47 (78.3%)	0.48
Ascites	34 (53.1%)	35 (58.3%)	0.59
Raised JVP	42 (65.6%)	35 (58.3%)	0.46

^*Indicates significant difference

NYHA, New York Heart Association; JVP, jugular venous pressure

Etiology, risk factors, and comorbidities

TB was the most common etiology identified in 64 (51.6%) patients. Hypoproteinemia (serum albumin < 3.5 g/dl) was the commonest comorbidity seen in 51 (41%), followed by diabetes mellitus in 13 (10.5%), hypothyroidism in 11 (9%), and anemia in 10 (8%) patients. The other less commonly associated comorbidities were coronary artery disease (CAD) in 8 (6.5%), hypertension in 7 (5.6%), chronic liver disease (CLD) in 6 (4.8%), chronic kidney disease (CKD) in 3 (2.5%), beta thalassemia in 2 (1.6%), and acute lymphoblastic leukemia (ALL) in 1 (0.8%) patient. Twelve patients (9.6%) had history of smoking. There were 23 (18.5%) patients who were on high doses of diuretics (≥ 80 mg/day furosemide equivalent) [10, 11], of which 16 (70%) belonged to NYHA class III or IV. The comparison between the 2 subgroups has been depicted in Table 2.

Table 2.

Comparison of comorbidities between TB and non-TB groups

	TB (n = 64)	Non-TB (n = 60)	P value
Hyperbilirubinemia	32 (50%)	32 (53.3%)	0.72
Hypoproteinemia	28 (43.8%)	23 (38.3)	0.46
Diabetes mellitus	5 (8%)	8 (13.3%)	0.38
Smoking	6 (9.4%)	6 (10%)	1.0
Hypothyroidism	4 (6.25%)	7 (11.7%)	0.35
Anemia	4 (6.25%)	6 (10%)	0.52
Coronary artery disease	4 (6.25%)	4 (6.7%)	1.0
Hypertension	2 (3.1%)	5 (8.3%)	0.26
Chronic liver disease	2 (3.1%)	4 (6.7%)	0.43
Chronic kidney disease	0 (0%)	3 (5%)	0.1
Empyema thoracis	3 (4.7%)	1 (1.7%)	0.61
Hematological problems	2 (3.1%)	1 (1.7%)	1.0

Pre-operative investigations

Hyperbilirubinemia (serum total bilirubin > 1 mg/dl) was the most commonly associated biochemical derangement seen in 64 (51.6%) patients. Chest radiograph and CT showed pleural effusion in 80 (64.5%) patients. Atrial fibrillation (AF) was detected in the electrocardiogram (ECG) of 8 (6.5%) patients. Echocardiography revealed mitral regurgitation (MR) in 9 (7.3%) and tricuspid regurgitation (TR) in 4 (3.2%) patients. The ejection fraction (EF) and tricuspid annular plane systolic excursion (TAPSE) of the subgroups have been depicted in Table 3. MR and TR of more than moderate grade were considered risk factors for surgery. The average pericardial thickness in the CT was 6.85 mm (Table 3). The incidence of pericardial calcification was significantly more in the non-TB subset. The various laboratory parameters of the cohort have been summarized in Table 3.

Table 3.

Comparison of pre-operative investigations between TB and non-TB groups

	TB (n = 64)	Non-TB (n = 60)	P value
Pleural effusion	44 (68.75%)	36 (60%)	0.35
Atrial fibrillation	0 (0%)	8 (13.3%)	0.002*
Mitral regurgitation	2 (3.1%)	7 (11.6%)	0.08
Tricuspid regurgitation	2 (3.1%)	2 (3.3%)	1.0
Ejection fraction in % (mean ± SD)	58.24 ± 4	58.17 ± 4	0.92
TAPSE in mm (mean ± SD)	17.1 ± 2.5	17.2 ± 2.3	0.81
Pericardial thickness in mm in CT (mean ± SD)	7.17 ± 2.95	6.5 ± 3.09	0.21
Pericardial calcification in CT	11 (17.2%)	22 (36.7%)	0.01*
Hemoglobin in g/dl (mean ± SD)	12.43 ± 1.75	12.11 ± 1.79	0.31
Serum total bilirubin in mg/dl (mean ± SD)	1.24 ± 0.82	1.38 ± 1.38	0.49
Serum albumin in g/dl (mean ± SD)	3.55 ± 0.6	3.6 ± 0.8	0.69
Serum creatinine in mg/dl (mean ± SD)	0.78 ± 0.23	0.93 ± 0.69	0.1

^*Indicates significant difference

TAPSE, tricuspid annular planar systolic excursion

Surgery performed

Conventional CAP was performed in 122 (98.3%) patients. Surgery was less than complete in 2 (1.6%) patients, who, however, had their right ventricular outflow and inflow regions cleared. These two patients belonged to NYHA class III pre-operatively. None of our patients required CPB. There were 4 (3.2%) patients with synchronous empyema thoracis, who underwent a decortication along with CAP. Out of the 8 (6.4%) patients with CAD diagnosed in the coronary angiogram, 4 had minor diseases which were managed medically, two underwent percutaneous intervention after the CAP (4–6 weeks), one had a simultaneous off-pump single arterial bypass grafting done, and one patient died in the immediate post-operative period due to myocardial infarction.. The intra-operative details are given in Table 4.

Table 4.

Comparison of surgical outcomes between TB and non-TB groups

	TB (n = 64)	Non-TB (n = 60)	P value
Pre-operative CVP in mmhg (mean ± SD)	20.48 ± 5.6	18.13 ± 4.1	0.004*
Post-operative CVP in mmhg (mean ± SD)	10.05 ± 4.02	8.13 ± 2.7	0.002*
ICU stay in hours (mean ± SD)	81.52 ± 14.64	76.5 ± 11.42	0.03*
Hospital stay in days (mean ± SD)	13.3 ± 7	10.7 ± 6	0.028*
Operative time in minutes (mean ± SD)	107.1 ± 34	90 ± 18.9	0.0008*
Blood loss in ml (mean ± SD)	205 ± 110	157.1 ± 113.4	0.02*
CAP + decortication	3 (4.7%)	1 (1.7%)	0.61
CAP + OPCAB	0	1 (1.7%)	0.48
Post-operative complications	5 (7.8%)	2 (3.3%)	0.44
In-hospital mortality (< 30 days from surgery)	1 (1.5%)	2 (3.3%)	0.61

^*Indicates significance

CVP, central venous pressure; ICU, intensive care unit; CAP, complete anterior pericardiectomy; OPCAB, off-pump coronary artery bypass surgery

Post-operative period

The median ICU stay was 72 h and the median hospital stay was 10 days (IQR — 7 to 15). Both the parameters were significantly higher in the TB subgroup (Table 4). Thirty (24%) patients had prolonged ICU stay. Of these 30, 29 had longer hospital stay also. Eight (6.5%) patients who had prolonged hospital stay had only a routine 72-h ICU stay. Hence, a total of 38 (31%) patients had prolonged ICU and/or hospital stay. There were a total of 7 (5.6%) post-operative complications and 3 (2.4%) in-hospital mortalities (within 30 days from surgery), in the study population. The median post-operative ventilation time was 14 h. The comparison between the two subgroups has been shown in Table 4. The independent variables that were analyzed which might have predicted adverse outcomes are depicted in Table 5. The result of the multivariate analysis is shown in Table 6. The total number of adverse outcomes was 48 (39%). As 4 out of the 10 patients with post-operative complication or in-hospital mortality also had either prolonged ICU stay or hospital stay, after adjusting for that, the total number of adverse outcomes considered for analysis was 44 (35.5%). The post-operative adverse events are summarized in Table 7.

Table 5.

Univariate analysis of pre-operative variables

Variable		Number of patients (124)	Adverse events (44)	No adverse events (80)	COR (95% CI)#	P value
Age less than 40 years	Yes	89 (72%)	36 (82%)	53 (65%)	2.1 (0.9–4.6)	0.07*
	No	35 (28%)	8 (18%)	27 (35%)
Male sex	Yes	94 (76%)	39 (89%)	55 (68%)	3.45 (1.2–10)	0.02**
	No	30 (24%)	5 (11%)	25 (32%)
NYHA class III/IV	Yes	33 (27%)	16 (36%)	17 (21%)	2.2 (0.9–5.1)	0.08*
	No	91 (73%)	28 (64%)	63 (79%)
Duration of symptoms more than 12 months	Yes	90 (73%)	33 (75%)	57 (71%)	1.1 (0.6–2.7)	0.68
	No	34 (27%)	11 (25%)	23 (29%)
Tubercular etiology	Yes	64 (52%)	31 (71%)	33 (41%)	4.0 (1.4–7.2)	0.008**
	No	60 (48%)	13 (29%)	47 (59%)
Raised JVP	Yes	77 (62%)	32 (73%)	45 (56%)	1.9 (0.89–4.5)	0.09*
	No	47 (38%)	12 (27%)	35 (44%)
Pleural effusion	Yes	80 (65%)	37 (84%)	43 (54%)	4.5 (1.8–11)	0.009**
	No	44 (35%)	7 (16%)	37 (46%)
Ascites	Yes	69 (56%)	31 (71%)	38 (47%)	3.1 (1.1–5.6)	0.01**
	No	55 (44%)	13 (29%)	42 (53%)
Hypoproteinemia	Yes	51 (41%)	24 (55%)	27 (34%)	2.6 (1.06–6.8)	0.04**
	No	73 (59%)	20 (45%)	53 (66%)
Hyperbilirubinemia	Yes	64 (52%)	24 (55%)	40 (50%)	1.2 (0.6–3.4)	0.6
	No	60 (48%)	20 (45%)	40 (50%)
Anemia	Yes	10 (8%)	4 (9%)	6 (8%)	1.3 (0.3–5.0)	0.8
	No	114 (92%)	40 (91%)	74 (92%)
Atrial fibrillation	Yes	8 (6.5%)	3 (7%)	5 (6%)	1.1 (0.3–4.9)	1.0
	No	116 (93.5%)	41 (93%)	75 (94%)
Mitral regurgitation	Yes	9 (7%)	5 (11%)	4 (5%)	1.9 (0.9–4.4)	0.09*
	No	115 (93%)	39 (89%)	76 (95%)
Tricuspid regurgitation	Yes	4 (3%)	2 (5%)	2 (3%)	1.2 (0.5–4.1)	0.79
	No	120 (97%)	42 (95%)	78 (97%)
Coronary artery disease	Yes	8 (6.5%)	3 (7%)	5 (6%)	1.05 (0.2–3.9)	0.9
	No	116 (93.5%)	41 (93%)	75 (94%)
Pericardial thickness > 7 mm	Yes	36 (29%)	17 (39%)	19 (24%)	1.9 (0.89–4.1)	0.08*
	No	88 (71%)	27 (61%)	61 (76%)
Calcified pericardium	Yes	33 (27%)	13 (30%)	20 (25%)	1.1 (0.7–6.1)	0.6
	No	91 (73%)	31 (70%)	60 (75%)
Pre-operative CVP > 18mmhg	Yes	76 (61%)	32 (73%)	44 (55%)	2.1 (1.2–4.5)	0.045**
	No	48 (39%)	12 (27%)	36 (45%)

NYHA, New York Heart Association; JVP, jugular venous pressure; CVP, central venous pressure

^*Denotes p value < 0.1

^**Denotes p value < 0.05

^#Crude odds ratio (95% confidence interval)

Table 6.

Multivariate logistic regression analysis

Variable (n)	Adverse outcomes (n = 44)		Post-operative complications and in-hospital mortality (n = 10)
	AOR (95% CI)#	P value	AOR (95% CI)#	P value
Age less than 40 years (89)	1.64 (0.72–3.76)	0.23	1.1 (0.65–5.8)	0.77
Male sex (94)	2.7 (1.06–6.89)	0.037*	1.3 (0.26–6.49)	0.74
NYHA class III/IV (33)	1.46 (0.65–3.28)	0.35	4.83 (1.26–18.4)	0.02*
Tubercular etiology (64)	2.37 (1.12–5)	0.02*	1.44 (0.38–5.4)	0.58
Pleural effusion (80)	2.58 (1.14–5.8)	0.02*	2.33 (0.47–11.5)	0.29
Ascites (69)	2.2 (1.04–4.7)	0.037*	1.95 (0.48–7.95)	0.34
Raised JVP (77)	1.6 (0.7–3.4)	0.2	3.75 (0.7–23)	0.2
Hypoproteinemia (51)	1.8 (0.86–3.78)	0.1	1.47 (0.4–5.39)	0.55
Mitral regurgitation (9)	1.29 (0.32–5.06)	0.7	3.8 (0.67–21.5)	0.12
Pericardial thickness > 7 mm (33)	1.19 (0.53–2.6)	0.6	1.05 (0.25–4.31)	0.07
Pre-operative CVP > 18mmhg (76)	1.29 (0.6–2.69)	0.49	2.7 (0.54–13.3)	0.22

^#Adjusted odds ratio (95% confidence interval)

^*Denotes significant p value

NYHA, New York Heart Association; JVP, jugular venous pressure; CVP, central venous pressure

Table 7.

Post-operative adverse events

	TB (n = 64)	Non-TB (n = 60)	P value
Prolonged ICU stay	21 (33%)	9 (15%)	0.02*
Prolonged hospital stay	26 (41%)	11 (18%)	0.007*
Re-admission due to CCF	2 (3.1%)	1 (1.7%)	1.0
Prolonged ventilation	1 (1.5%)	1 (1.7%)	1.0
Chylothorax	1 (1.5%)	0 (0%)	1.0
Sternal wound infection	1 (1.5%)	0 (0%)	1.0
In-hospital mortality	1 (1.5%)	2 (3.3%)	0.61

^*Denotes significance

CCF, congestive cardiac failure

Post-operative investigations

Histopathology revealed necrotizing granulomatous inflammation in 64 (51.6%) patients and chronic non-specific inflammation in 60 (48.4%) patients. Microbiological studies showed Mycobacterium tuberculosis (MTB) in 22 (17.8%), methicillin-resistant Staphylococcus aureus (MRSA) in 3 (2.4%), coagulase-negative Staphylococcus (CONS) in 3 (2.4%), and non-fermenting gram-negative bacteria (NFGNB) in 1 (0.8) patient.

One-year follow-up data

A total of 121 (97.6%) patients reported for follow-up at 3 months and at the end of 1 year after CAP. The symptomatic improvement has been shown in Table 8. After excluding the in-hospital mortality, 101 (83.5%) of the 121 patients were lost to follow-up after 1 year. Active follow-up to trace these patients was not carried out. There were 5 (4%) patients who had findings suggestive of recurrent constrictive physiology on echocardiography done at 1 year but since they did not have any symptoms, they were advised to be on follow-up. There were 4 (3.2%) patients whose symptoms deteriorated from NYHA class I at 3 months to NYHA class II at 1 year. The echocardiography parameters at 1 year are mentioned in Table 8.

Table 8.

Follow-up details

	TB (n = 64)	Non-TB (n = 60)	P value
Mitral regurgitation at 1 year	1 (1.5%)	2 (3.3%)	0.7
Tricuspid regurgitation at 1 year	2 (3.1%)	2 (3.3%)	1.0
Ejection fraction in % (mean ± SD) after 1 year	60.1 ± 3.5	61.06 ± 3.8	0.8
TAPSE in mm (mean ± SD) after 1 year	19.8 ± 1.5	20.3 ± 1.4	0.7
NYHA class I at discharge	61 (95.3%)	57 (95%)	1.0
NYHA class I at 3 months	63 (98.4%)	58 (96.7%)	0.61

NYHA, New York Heart Association

Discussion

Our cohort of 124 patients over a period of 12 years is quite large and will provide valuable input in the management of CCP. Younger people were most commonly affected, contrary to the western literature, but confirming with Indian literature [2–4]. This was due to the higher prevalence of TB in India with a higher incidence in the youth [12]. The sex ratio was similar to other studies [2–4]. Most of our patients belonged to NYHA class II, contrary to other studies where most of them belonged to NYHA class III or IV [2–4, 13, 14]. This could be because most of our patients were medically optimized by the physicians, before they presented to the surgeon. This medical optimization could be the reason for the relatively less number of patients with raised JVP when compared to other studies [4]. Patients on diuretics with relative hypovolemia will not have raised JVP [15]. The duration of symptoms was significantly higher in the non-TB subset, which showed that idiopathic, uremic, and other etiologies take a longer time to develop into a CCP and warrant a pericardiectomy, when compared to TB. TB was the most common etiology seen in 64 (51.6%) patients, which was due to the high prevalence in the country [16]. About 100 (80.6%) patients had a prior history of ATT. In our study, the diagnosis of TB was made by histopathological and culture studies of the excised pericardium. The incidence of TB might be even higher, since the mycobacterium and the characteristic histopathological findings of TB might have disappeared after effective ATT [17]. The other etiologies in our cohort were CLD in 6 (4.8%), uremia in 3 (2.5%), and hematological diseases in 3 (2.5%) patients. These abovementioned rarer pathologies cause repeated pericardial effusions, which, over a period of time, may lead to CCP. In the western literature, post-surgical and radiation-related etiologies were more common, in contrast to our cohort [2, 3]. In the remaining 48 (39%) patients, the cause of CCP was not known. Hypothyroidism was associated in 11 (23%) of these 48 patients and whether it could be one of the probable etiologies for idiopathic CCP has to be further investigated [18, 19]. Hyperbilirubinemia was the most common abnormal laboratory finding, as CCP often leads to congestive hepatopathy [20]. This hepatopathy might also be the reason for the high incidence of hypoproteinemia in the study [20]. Protein losing enteropathy, often associated with CCP, may also contribute to the hypoproteinemia [13]. The incidence of pleural effusion − 80 (64.5%) and ascites 69 (55.6%) were higher in our patients, more than in other reported studies [4, 21]. Besides causing severe constriction [14], primary tuberculous involvement of the pleura, lungs, peritoneum, and abdominal organs might have increased the incidence of pleural effusion and ascites. Most Indian patients present late with established severe malnutrition syndromes, cachexia of chronic disease, and hypoproteinemia, which might have further increased the incidence of ascites and pleural effusion [22]. The presence of pericardial calcification and incidence of AF and MR were more in the non-TB subset, as the disease process was more chronic in them, leading to dilatation of the atria and calcification of the pericardium. These factors, however, did not affect the surgical outcomes in our study.

The pre-operative CVP was significantly higher in the TB group (p = 0.004), which might be because of the extensive, intense inflammatory process and fibrosis innate to TB, which leads to severe constriction [14]. Tuberculous pericardium was also densely adherent to the myocardium, resulting in increased blood loss and operative time in the TB group. Four patients from the TB group had a decortication of the lung done along with CAP which would have increased the operative time in those patients. The ICU stay and hospital stay were significantly higher in the TB group (p = 0.03). In TB patients, the myocardium, after being released from the constriction, required a longer period of time to recover, due to its atrophy caused by the intense constriction. The associated pleural effusion and hypoproteinemia caused the intercostal tubes to drain longer, thus contributing to a longer hospital stay. After surgery, there was a significant drop in CVP in both the groups due to complete right ventricular inflow and outflow clearance. As the pre-operative CVP was lower in the non-TB group to start with, there was a less dramatic post-operative drop of the same in this group, when compared to the TB group.

The post-operative morbidity of 7 (5.6%) and in-hospital mortality of 3 (2.4%) patients reported in our study were comparable or lesser than other studies [2–5]. Our surgical outcomes have improved significantly from our previous published experience [13]. The common complications were re-admission with CCF (2.4%) and prolonged ventilation (1.6%). The rarer complications seen were chylothoraces (0.8%) and sternal wound infections (0.8%). There were 3 mortalities in the study. Two of them were due to post-operative refractory low cardiac output syndromes. One patient who was planned for a percutaneous coronary intervention post-operatively after discharge died due to acute myocardial infarction on 7th post-operative day. Multivariate analysis of the pre-operative variables revealed that male sex (OR—2.7, p—0.037), tubercular etiology (OR—2.37, p—0.02), presence of pleural effusion (OR—2.58, p—0.02), and ascites (OR—2.2, p—0.037) significantly affected outcomes. TB and CCP affected males predominantly and that might be the reason for the higher incidence of adverse outcomes in them. The presence of pleural effusion and ascites indicates that the CCP was severe and that the CCF was not getting adequately optimized by the pre-operative therapies. Hypoproteinemia and TB also would have increased the incidences of pleural effusion and ascites which in turn affected outcomes. Although hypoproteinemia affected outcomes in univariate analysis, it did not reach statistical significance after elimination of confounding factors by multivariate analysis. Factors like older age, renal dysfunction, AF, TR, lower EF, and CAD also did not affect the morbidity or mortality contrary to other studies [2, 5, 23]. This is probably because the incidences of the abovementioned variables in our cohort were too low to generate statistical significance.

During analysis of the individual components of the composite adverse outcome, it was noted that, although TB significantly affected ICU and hospital stay, it did not translate into it affecting morbidity or mortality (Table 7). Hence, a separate regression analysis was done in which only post-operative complications and in-hospital mortality were considered as adverse outcomes. This analysis determined that TB, male gender, presence of pleural effusion, and ascites predicted adverse outcomes only due to their effect on prolonging ICU and hospital stay. These factors did not affect morbidity or mortality. Patients belonging to NYHA class III/IV had increased mortality and morbidity, which was significant (OR—4.83, p—0.02), reiterating the fact that optimization of pre-operative CCF is paramount to get better results out of pericardiectomy.

MTB isolation in cultures was achieved only in 22 (17.7%) patients, since most of the patients had at least completed the intensive phase of ATT at the time of for surgery. Our 1-year follow-up data indicates that a pericardiectomy leads to significant alleviation of symptoms in patients with CCP, thus reiterating the fact that pericardiectomy is the gold standard in the management for CCP with minimal morbidity and mortality. Even the two patients, who had incomplete pericardiectomy, had no symptom progression in the follow-up. A small number of patients (5, 4%) showed recurrent features of constrictive physiology in their follow-up echocardiography at a year’s time, but did not have any worsening of symptoms. A constrictive scar over the myocardium may form in certain patients due to an inflammatory response to surgery, which mimics CCP in the echocardiogram [24]. Four (3.2%) patients had worsened to NYHA class II at the end of 1 year. Two were due to progression of TR and in the other 2, the cause was not elucidated. They improved with optimization of medical therapy. The good outcomes in our study were due to the intense pre-operative optimization of CCF with adequate diuretics, pre-operative correction of hypoproteinemia and attention to the risk factors to the extent possible, diligent complete pericardiectomy, and aggressive ICU management with ventilation, inotropes, diuretics, and digoxin.

Limitations

The major limitations of the study were its retrospective nature and the lack of long-term follow-up. The follow-up was not long enough to assess late recurrences and complications. Most of our patients were from remote areas which made it impossible for them to come for regular follow-up, especially when they were asymptomatic. The actual incidence of TB might have been much higher, since there could have been some false-negative TB patients, since we included only post-operative biopsy and/or culture-proven TB patients in that group. As an institutional protocol, if the patient showed symptomatic improvement, immediate post-operative echocardiogram was not considered necessary to objectively analyze the improvement after surgery.

Conclusion

Pericardiectomy continues to be the standard operation for CCP and can be executed in all patients with CCP, with acceptable morbidity and mortality. Surgery in TB CCP is significantly difficult when compared with other etiologies. Our study concludes that although TB did not affect mortality or morbidity, it significantly affected ICU and hospital stay in patients undergoing this surgery. Pre-operative CCF and hypoproteinemia are important risk factors to be considered in the management of CCP.

Author contribution

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Santhosh Regini Benjamin, Aamir Mohammad, Ravi Shankar, and Premprasath Kesavan. The first draft of the manuscript was written by Santhosh Regini Benjamin and all authors commented on previous versions of the manuscript before the final one. The surgeries were performed by Korah Thomas Kuruvilla, Madhu Andrew Philip, and Roy Thankachen. The final manuscript was written by Santhosh Regini Benjamin and Birla Roy Gnanamuthu. All authors read and approved the final manuscript.

Funding

None.

Declarations

Ethics approval

The approval of the institutional review board was obtained.

Informed consent

Written consent for study and publication were obtained from the patients prior to the surgery.

Human and animal rights

The study has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Conflict of interest

There was no conflict of interest in this study.