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\begin{document}

\title{Outcomes of Pericardiectomy for Constrictive Pericarditis following
Mediastinal Irradiation}



\author[1]{Siddharth Pahwa}%
\author[2]{Juan A. Crestanello}%
\author[2]{William R. Miranda}%
\author[2]{Annalisa Bernabei}%
\author[2]{Andreas Polycarpou}%
\author[2]{Hartzell Schaff}%
\author[2]{Joseph Dearani}%
\author[3]{John Stulak}%
\author[2]{Alberto Pochettino}%
\author[2]{Richard Daly}%
\author[2]{Brian Lahr}%
\author[2]{Jason Viehman}%
\author[4]{Kevin Greason}%
\affil[1]{University of Louisville}%
\affil[2]{Mayo Clinic}%
\affil[3]{Mayo Clinc}%
\affil[4]{MAYO CLINIC}%


\vspace{-1em}



  
  \date{May 17, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background Pericardiectomy for post-radiation constrictive pericarditis
has been reported to generally have unfavorable outcomes. This study
sought to evaluate surgical outcomes in a large cohort of patients
undergoing pericardiectomy for radiation-associated pericardial
constriction. Methods A retrospective analysis of all patients
([?]18years) who underwent pericardiectomy for a diagnosis of constrictive
pericarditis with a prior history of mediastinal irradiation from June
2002 to June 2019 was conducted. There were 100 patients (mean age
57.2\selectlanguage{ngerman}±10.1 years, 49\% females) who met the inclusion criteria. Records
were reviewed to look at surgical approach, extent of resection, early
mortality and late survival. Results The overall operative mortality was
10.1\% (n=10). The rate of operative mortality decreased over the study
period; however, the test of trend was not statistically significant
(P=0.062). Hodgkin's disease was the most common malignancy (64\%) for
which mediastinal radiation had been received. Only 27\% patients had an
isolated pericardiectomy, and concomitant pericardiectomy and valve
surgery was performed in 46\% patients. Radical resection was performed
in 50\% patients, whereas 47\% patients underwent a subtotal resection.
Prolonged ventilation (26\%), atrial fibrillation (21\%) and pleural
effusion (16\%) were the most common post-operative complications. The
overall 1,5- and 10-years survival was 73.6\%, 53.4\% and 32.1\%
respectively. Increasing age (HR 1.044, 95\%CI 1.017-1.073) appeared to
have a significant negative effect on overall survival in the univariate
model. Conclusion Pericardiectomy performed for radiation associated
constrictive pericarditis has poor long-term outcomes. The early
mortality, though high (\textasciitilde{}10\%), has been showing a
decreasing trend in the test of time.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Outcomes of Pericardiectomy for Constrictive Pericarditis
following Mediastinal Irradiation}

Siddharth Pahwa, MD\textsuperscript{1}, Juan Crestanello,
MD\textsuperscript{1}, William Miranda, MD\textsuperscript{2}, Annalisa
Bernabei, MD\textsuperscript{1}, Andreas Polycarpou,
MD\textsuperscript{1}, Hartzell Schaff, MD\textsuperscript{1}, Joseph
Dearani, MD\textsuperscript{1}, John Stulak, MD\textsuperscript{1},
Alberto Pochettino, MD\textsuperscript{1}, Richard Daly,
MD\textsuperscript{1}, Brian Lahr\textsuperscript{3}, Jason
Viehman\textsuperscript{3}, Kevin Greason, MD\textsuperscript{1}

\textbf{Institutions}

1 -- Department of Cardiovascular Surgery, Mayo Clinic, Rochester, MN,
USA

2 -- Department of Cardiology, Mayo Clinic, Rochester, MN, USA

3 -- Division of Biomedical Statistics and Informatics, Mayo Clinic,
Rochester, MN, USA

\textbf{Meeting presentation} -- Society of Thoracic Surgeons (STS),
2021 as an On-Demand presentation, January 29-31, 2021

\textbf{Word count} -- 3530

\textbf{Corresponding author} -- Juan Crestanello, MD

Department of Cardiovascular Surgery

Mayo Clinic, Rochester, MN, USA

Phone -- 507-255-7066

Email -- crestanello.juan@mayo.edu

\textbf{Abstract}

\emph{Background}

Pericardiectomy for post-radiation constrictive pericarditis has been
reported to generally have unfavorable outcomes. This study sought to
evaluate surgical outcomes in a large cohort of patients undergoing
pericardiectomy for radiation-associated pericardial constriction.

\emph{Methods}

A retrospective analysis of all patients~([?]18years)~who
underwent~pericardiectomy for a diagnosis of constrictive pericarditis
with a prior history of mediastinal irradiation from June 2002 to June
2019 was conducted. There were 100 patients (mean age 57.2\selectlanguage{ngerman}±10.1 years,
49\% females) who met the inclusion criteria. Records were reviewed to
look at surgical approach, extent of resection, early mortality and late
survival.

\emph{Results}

The overall operative mortality was 10.1\% (n=10). The rate of operative
mortality decreased over the study period; however, the test of trend
was not statistically significant (P=0.062). Hodgkin's disease was the
most common malignancy (64\%) for which mediastinal radiation had been
received. Only 27\% patients had an isolated pericardiectomy, and
concomitant pericardiectomy and valve surgery was performed in 46\%
patients. Radical resection was performed in 50\% patients, whereas 47\%
patients underwent a subtotal resection. Prolonged ventilation (26\%),
atrial fibrillation (21\%) and pleural effusion (16\%) were the most
common post-operative complications. The overall 1,5- and 10-years
survival was 73.6\%, 53.4\% and 32.1\% respectively. Increasing age (HR
1.044, 95\%CI 1.017-1.073) appeared to have a significant negative
effect on overall survival in the univariate model.

\emph{Conclusion}

Pericardiectomy performed for radiation associated constrictive
pericarditis has poor long-term outcomes. The early mortality, though
high (\textasciitilde{}10\%), has been showing a decreasing trend in the
test of time.

Keywords -- mediastinal irradiation, pericardiectomy, operative
mortality

\textbf{Abbreviations}\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
RACD & Radiation-associated cardiac disease\tabularnewline
\midrule
\endhead
NYHA & New York Heart Association\tabularnewline
CPB & Cardio-pulmonary bypass\tabularnewline
\bottomrule
\end{longtable}

\textbf{Introduction}

Mediastinal radiotherapy has been widely used over the years and has
evolved to become one of the cornerstones of treatment for various types
of thoracic cancers.\textsuperscript{1} However, the proximity of the
radiation field to the heart can result in a sustained dose to
cardiovascular structures, leading to radiation-associated cardiac
disease (RACD).\textsuperscript{2} The cardiovascular complications of
radiation include myocardial fibrosis, valvular abnormalities, coronary
artery disease, pericarditis and conduction system
dysfunction.\textsuperscript{3} While acute pericarditis has now become
less common with modern radiation protocols, chronic pericarditis may
manifest decades after treatment completion, often with resultant
constriction.\textsuperscript{4}

Constrictive pericarditis leads to a loss of pericardial compliance,
with resultant diastolic heart
failure.\textsuperscript{5}Pericardiectomy has been the treatment of
choice for constrictive pericarditis, resulting in symptomatic relief
and improvement in functional status.\textsuperscript{6-11}
Pericardiectomy performed for post-radiation constriction has been
reported to generally have unfavorable outcomes but data are limited to
small-sized studies\textsuperscript{7, 11-13}. We sought to evaluate
outcomes in a large cohort of patients undergoing pericardiectomy for
constriction after mediastinal irradiation, and to analyze surgical
approach, extent of resection, early mortality, and late survival.

\textbf{Methods}

We retrospectively reviewed 130 adult patients (age [?] 18 years) who
underwent pericardiectomy with a prior history of mediastinal
irradiation, from June 2002 to June 2019 at the Mayo Clinic in
Rochester, Minnesota. Both primary and re-operative procedures were
included. The study was approved by the Institutional Review Board at
Mayo Clinic, Rochester, Minnesota (Date 2/8/2019, IRB no - 19-000542).
Individual patient consent requirement was waived as the study was
deemed a minimal-risk retrospective study; 2 patients without research
authorization were excluded. Patient characteristics were obtained from
the prospectively collected database based on definitions set forth by
the Society of Thoracic Surgeons (STS) Adult Cardiac Database with
additional review of patient records for supplementing missing
information.\textsuperscript{14}

Patients who underwent pericardiectomy for an indication other than a
pre-operative diagnosis of constriction (N=28) were excluded, leaving
100 patients for study inclusion. Our surgical approach and operative
techniques for pericardiectomy have been previously
reported.\textsuperscript{7, 10, 15-17} A radical resection was defined
as removal of anterior, inferior (diaphragmatic) and lateral pericardium
posterior to the phrenic nerves. Any pericardial resection that did not
meet the criteria for radical resection was defined as subtotal
resection. Operative mortality was defined as any death, regardless of
cause, occurring within 30 days after surgery, or during the same
hospitalization as the index surgery, regardless of time.

\emph{Statistical analysis}

Continuous variables are reported as median (interquartile range
{[}IQR{]}), and categorical variables are reported as number
(percentage). The temporal trend in operative mortality over the study
period was visualized with a Loess smoothing estimator and was formally
tested with a Wilcoxon rank sum test. Long-term mortality was depicted
graphically using the Kaplan-Meier estimator, and the reverse
Kaplan-Meier method was used to summarize follow-up time. The unadjusted
association between select baseline factors and mortality was assessed
in univariable Cox proportional hazards models. Because few of the
patients (3 patients) underwent completion pericardiectomy, this group
was combined with the radical pericardiectomy group. These analyses were
done in SAS version 9.4 (SAS Institute, Cary NC).

\textbf{Results}

The study included a total of 100 adult patients with a history of prior
mediastinal irradiation who underwent pericardiectomy for constriction
(median (IQR) age 56.8 (50.9, 65.9) years, 49\% females). Demographic
characteristics are shown in Table 1. Hodgkin's disease was the most
common malignancy (64\%) for which mediastinal radiation had been
received, followed by breast cancer (15\%). Most of the patients (75\%)
had New York Heart Association (NYHA) class III/IV symptoms at
presentation. Pericardiectomy was the first cardiovascular surgical
procedure in 66\% of patients. The median (IQR) duration between
mediastinal irradiation and surgery was 28.5 (20, 34) years.

The operative characteristics are outlined in Table 2. The surgical
approach was by a full midline sternotomy in 95\% of patients, and
cardio-pulmonary bypass was used in 96\%. Only 27\% of patients had an
isolated pericardiectomy. A radical resection was performed in 50\% of
patients, whereas 47\% underwent a subtotal resection.

\emph{Early outcomes}

Overall, the rate of operative mortality was 10.1\%. This rate appeared
to show a decreasing trend over the study period, although the test for
trend was not statistically significant (P=0.06) (Figure 1). Prolonged
ventilation (26\%), atrial fibrillation (21\%) and pleural effusion
(16\%) were the most common post-operative complications (Table 3).
Post-operative dialysis was needed in 13 (13\%) patients.

\emph{Late outcomes}

A total of 52 deaths (early or late) were observed over a median (IQR)
follow-up period of 6.01 (3.56, 9.47) years. The overall 1-, 5- and
10-year survival was 73.6\%, 53.4\% and 32.1\% respectively (Figure 2).
The prespecified factors assessed for an unadjusted association with
overall survival are presented in Table 4. Only older age was
univariably associated with increased risk of mortality (per 10-year
increase: HR 1.55, 95\% CI 1.18-2.02; p=0.002). There was no association
between ejection fraction, coronary artery disease, previous cardiac
surgery, concomitant surgical procedures, or pre-operative renal failure
with mortality. There was no survival advantage of performing a radical
resection in this population (HR 1.35, 95\% CI 0.77-2.36, p=0.295).
There was also no difference in survival between patients that underwent
pericardiectomy with concomitant cardiac procedures and patients that
underwent isolated pericardiectomy (HR 0.70, 95\% CI 0.39-1.27,
p=0.246).

\textbf{Discussion}

This study shows that pericardiectomy for constriction in patients with
prior mediastinal irradiation is associated with poor long-term
survival. The 1, 5- and 10-year survival was 74\%, 53\% and 32\%
respectively. Early mortality, though high (\textasciitilde{}10\%) for
the entire period, showed a modest, yet statistically nonsignificant,
decreasing trend over time, with mortality rates over the second half of
the period (approximately 4\%; 2 deaths in 51 surgeries) being more
comparable to those with non-radiation related constriction.

Radiation induced pericardial disease is one of the most common
manifestations of RACD. This typically manifests itself several years
after mediastinal irradiation. In the present study, the median duration
from radiation to pericardiectomy was 28.5 years (IQR 20-34 years). This
was a mean of 53 months as reported by Siefert and
colleagues\textsuperscript{18}, and a median of 11 years (range 2 to 30
years) as reported by Bertog and colleagues.\textsuperscript{11} Ling et
al reported a median range of 13 years\textsuperscript{7}, and McCaughan
et al reported a range of 15 months to 44 years.\textsuperscript{19}This
may also reflect improved cancer cure rates, which have resulted in
greater longevity and thus the likelihood of developing delayed
cardiovascular sequelae.\textsuperscript{7} In previous studies,
lymphomas have been the most common malignancy for which mediastinal
radiation was received, followed by breast cancer.\textsuperscript{7,
11, 18, 19} Our experience has been similar, with lymphomas constituting
69\% of the patients and breast cancer a further 15\%.

Clinical manifestation of pericardial disease may vary in severity from
asymptomatic pericardial effusion to debilitating constrictive
pericarditis.\textsuperscript{3, 4, 20} Fibrosis is a common sequela of
radiotherapy and leads to fibrous thickening of the pericardium. In
addition to pericardial fibrosis, there is myocardial fibrosis with
possible endocardial fibrosis as well.\textsuperscript{21} Brosius and
colleagues found interstitial myocardial fibrosis in patients who had
received prior irradiation.\textsuperscript{21} The pathogenesis of this
myocardial fibrosis has been related to capillary endothelial cell
injury, leading to a quantitative loss of capillaries, leading to
ischemia.\textsuperscript{22} It is perceived that the increased filling
pressures in these patients may be in part due to increased myocardial
stiffness, which may not be relieved even with an adequate pericardial
resection.

Pericardiectomy is also technically challenging in this subset of
patients. The plane of dissection may not be easily accessible due to
the dense mediastinal fibrosis. In the present study, a radical
resection could be performed in only 50\% of the patients, whereas 47\%
patients received a subtotal resection. This contrasts with previous
reports from this institution where radical pericardiectomy was
performed on 77\% of patients presenting with constriction for causes
other than radiation.\textsuperscript{10} Another indicator of the
technical difficulty could be the use of cardiopulmonary bypass (CPB) in
96\% of these patients. A previous report from this institution
documented the use of CPB to be 51\% in pericardiectomies performed for
constriction for causes other than radiation.\textsuperscript{10} This
maybe a reflection of the surgeon deeming it unsafe to perform a radical
resection in some patients due to the degree of difficulty of the
procedure and having a low threshold of going on CPB. Our experience was
corroborated by the findings of Ni and colleagues, who concluded that a
complete pericardiectomy may not be achieved in all patients with
post-radiation constrictive pericarditis.\textsuperscript{13}

Mediastinal irradiation damages the vascular endothelium and leads to
radiation-induced vascular disease of peripheral, coronary and carotid
arteries.\textsuperscript{23} When the coronary vasculature is involved,
these patients may present with the classical features of coronary
artery disease; however, some may also remain
asymptomatic.\textsuperscript{24, 25} Valvular disease is frequently
seen in this subset of patients as well. The aortic and mitral valves
are more commonly involved, and the affected valves are typically
fibrotic with focal dystrophic calcification and marked
thickening.\textsuperscript{21, 26, 27} In the present study too,
isolated pericardiectomy was performed in only 27\% of the patients,
with most of the patients having concomitant valve surgery (46\%),
coronary artery bypass grafting (4\%), or a combination of both
procedures (23\%). This further illustrates the pan-cardiac involvement
in these patients, further adding to the degree of complexity and
justifies the higher need for CPB in this population.

Pericardiectomy for post-irradiation constrictive pericarditis has been
reported to have high operative mortality with poor late results. Ni and
colleagues collected data from a series of 46 patients across literature
and reported an operative mortality of 22\%.\textsuperscript{13} Bertog
and colleagues also reported an operative mortality of 21\% in this
subset of patients in their large series on pericardiectomy for
constriction.\textsuperscript{11} The general belief is that the effects
of radiation on other cardiac structures, including coronary
vasculature, valvular abnormalities and the associated myocardial
fibrosis all contributes to the increased peri-operative mortality seen
in this subset. In the present study, the operative mortality was 10\%,
which is higher than the 2.5\% operative mortality reported by the same
institution for pericardiectomy for constriction performed for
etiologies other than mediastinal
irradiation.\textsuperscript{10}However, our data suggest an improvement
over time, based on a decreasing rate in operative mortality that
trended toward significance and an observed rate of 4\% over the second
half of the study. This maybe attributed to improved surgical and
perfusion techniques, post-operative care, and better patient selection.
Noteworthy, pericardiectomy was still associated with significant
morbidity, with 13\% of patients requiring post-operative dialysis.

The long-term outcomes of this patient population remain poor, with a 1,
5- and 10-year survival of 73\%, 53\% and 32\% respectively. Previous
reports from this institution have shown a 1, 5- and 10- year survival
of approximately 87\%, 77\% and 58\% respectively, for pericardiectomy
performed for all other etiologies of
constriction.\textsuperscript{10}The only risk factor associated with
increased mortality was advanced age which may reflect to medical
complexities with high prevalence of comorbidities (coronary artery
disease, valvular disorders, renal dysfunction). Despite the poor
long-term outcomes, whether pericardiectomy in this population of
patients is associated with significant improvements in functional
capacity and quality of life requires further investigation.

\textbf{Conclusion}

Patients with prior mediastinal irradiation undergoing pericardiectomy
for constrictive pericarditis in the current era have acceptable early
mortality, albeit still higher than in other etiologies of constriction;
however, the long-term prognosis in this population remains poor.

\textbf{Limitations}

There are several limitations to this study. First, it is a
retrospective single-institution study limited by its inherent selection
bias. Second, this retrospective study was conducted over a span of 18
years. The surgical techniques and definitions of post-operative
complications have continued to evolve and may have contributed to
variability of data over time. Lack of functional data, and a comparison
group of patients who had mediastinal irradiation induced constriction
but did not undergo pericardiectomy are other important limitations.

Sources of funding -- None declared

Conflict of interest -- None declared

Figure 1 -- Operative mortality. Test of trend over the study period

Figure 2 -- Late mortality at 1-, 5- and 10 years

Table 1 -- Patient demographics\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\begin{minipage}[b]{0.47\columnwidth}\raggedright\strut
\textbf{Variable}\strut
\end{minipage} & \begin{minipage}[b]{0.47\columnwidth}\raggedright\strut
\textbf{N=100}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Age (years), median (IQR)\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
56.8 (20.9, 65.9)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Female Sex, N (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
49 (49\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
BMI (kg/m\textsuperscript{2}), median (IQR)\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
26.1 (23.3, 29.0)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
BSA (m\textsuperscript{2}), median (IQR)\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
1.9 (1.7, 2.1)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Diabetes Mellitus, N (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
13 (13\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Dyslipidemia, N (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
69 (69\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Hypertension, N (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
43 (43\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
NYHA, N (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
I\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
3 (3\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
II\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
22 (22\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
III\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
57 (57\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
IV\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
18 (18\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Type of Malignancy, N (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Hodgkin's disease\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
64 (64\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Breast cancer\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
15 (5\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Non-Hodgkin's disease\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
5 (5\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Esophageal cancer\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
5 (5\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Thymic cancer\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
3 (3\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Lung cancer\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
4 (4\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Metastasis\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
4 (4\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Chronic Lung Disease type, N (\%) \selectlanguage{romanian}\textsuperscript{ǂ}\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
None\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
62 (63\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Interstitial fibrosis\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
19 (19\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Obstructive\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
13 (13\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Other\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
3 (3\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Multiple\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
2 (2\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Incidence of Cardiovascular Surgery, N (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
First surgery\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
66 (66\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
First redo\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
31 (31\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Second/higher redo\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
3 (3\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Previous CABG, N (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
20 (20\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Previous Valve Surgery, N (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
15 (15\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Previous PCI, N (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
18 (18\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Heart rhythm, N (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Sinus\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
80 (80\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Atrial fibrillation/flutter\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
5 (5\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
1\textsuperscript{st} degree AV block\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
15 (15\%)\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\selectlanguage{romanian}\textsuperscript{ǂ} Data was missing in 1 patient.

IQR -- Inter-quartile Range, BMI -- Body Mass Index, BSA -- Body Surface
Area, NYHA -- New York Heart Association, CABG -- Coronary Artery Bypass
Grafting, PCI -- Percutaneous Coronary Intervention, AV --
Atrio-ventricular

Table 2 -- Operative characteristics\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\begin{minipage}[b]{0.47\columnwidth}\raggedright\strut
\textbf{Variable, N (\%)}\strut
\end{minipage} & \begin{minipage}[b]{0.47\columnwidth}\raggedright\strut
\textbf{N=100}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Operative approach\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Full sternotomy\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
95 (95\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Partial sternotomy\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
2 (2\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Right thoracotomy\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
1 (1\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Left thoracotomy\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
1 (1\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Postero-lateral thoracotomy\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
1 (1\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Cardio-pulmonary bypass used\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
96 (96\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Operative Status\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Elective\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
80 (80\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Urgent\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
20 (20\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Operative category\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Isolated pericardiectomy\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
27 (27\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Pericardiectomy + CABG\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
4 (4\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Pericardiectomy + Valve surgery\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
46 (46\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Pericardiectomy + CABG + Valve surgery\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
23 (23\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Pericardiectomy type\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Radical\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
50 (50\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Subtotal\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
47 (47\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Completion\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
3 (3\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Pericardiectomy indication\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Constrictive\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
99 (99\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Effusive-constrictive\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
1 (1\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Use of intra-operative blood products \selectlanguage{romanian}\textsuperscript{ǂ}\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
69 (72\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Use of IABP\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
11 (11\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
ECMO used during hospitalization\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
4 (4\%)\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\selectlanguage{romanian}\textsuperscript{ǂ} Data was missing in 4 patients.

CABG -- Coronary Artery Bypass Grafting, IABP -- Intra-aortic Balloon
Pump, ECMO -- Extra-corporeal Membrane Oxygenation

Table 3 -- Post-operative complications\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\textbf{Variable, N (\%)} & \textbf{N=100}\tabularnewline
\midrule
\endhead
Operative mortality \selectlanguage{romanian}\textsuperscript{ǂ} & 10 (10\%)\tabularnewline
Prolonged Ventilation & 26 (26\%)\tabularnewline
Atrial fibrillation & 21 (21\%)\tabularnewline
Pleural Effusion & 16 (16\%)\tabularnewline
Dialysis required & 13 (13\%)\tabularnewline
Permanent Pacemaker Required & 6 (6\%)\tabularnewline
Sternal Infection & 6 (6\%)\tabularnewline
GI Event & 5 (5\%)\tabularnewline
Re-operation for Bleeding & 4 (4\%)\tabularnewline
Sepsis & 4 (4\%)\tabularnewline
Stroke & 1 (1\%)\tabularnewline
TIA & 1 (1\%)\tabularnewline
\bottomrule
\end{longtable}

\selectlanguage{romanian}\textsuperscript{ǂ} Data was missing in 1 patient.

GI -- Gastro-intestinal, TIA -- Transient Ischemic Attack

Table 4 -- Univariate association of factors with overall survival\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\textbf{Variable} & \textbf{Comparison} & \textbf{P Value} &
\textbf{Hazard Ratio (95\% CI)}\tabularnewline
\midrule
\endhead
Age & per 10-year increase & 0.002 & 1.55 (1.18-2.02)\tabularnewline
Gender & Female vs Male & 0.736 & 0.91 (0.52-1.58)\tabularnewline
NYHA Class & III/IV vs I/II & 0.791 & 1.09 (0.57-2.09)\tabularnewline
Preoperative Renal Failure & Yes vs No & 0.747 & 1.26
(0.31-5.23)\tabularnewline
Previous CVS & Yes vs No & 0.502 & 1.21 (0.70-2.10)\tabularnewline
Coronary Artery Disease & Yes vs No & 0.585 & 1.17
(0.66-2.09)\tabularnewline
EF \textless{} 50\% & Yes vs No & 0.835 & 0.92
(0.41-2.04)\tabularnewline
Pericardiectomy type & Radical/Completion vs Subtotal & 0.295 & 1.35
(0.77-2.36)\tabularnewline
Operative category & Concomitant vs isolated pericardiectomy & 0.246 &
0.70 (0.39-1.27)\tabularnewline
\bottomrule
\end{longtable}

CI -- Confidence Interval, NYHA -- New York Heart Association, CVS --
Cardiovascular Surgery, EF -- Ejection Fraction

\textbf{References}

\begin{enumerate}
\tightlist
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\item
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\item
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\item
  STS Adult Cardiac Surgery Database Data Specifications Version 2.81.
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\item
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\item
  Thompson JL, Burkhart HM, Dearani JA, Cetta F, Oh JK, Schaff HV.
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\item
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\item
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\item
  Orzan F, Brusca A, Conte MR, Presbitero P, Figliomeni MC. Severe
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\item
  Tamura A, Takahara Y, Mogi K, Katsumata M. Radiation-induced valvular
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\item
  Carlson RG, Mayfield WR, Normann S, Alexander JA. Radiation-associated
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\end{enumerate}

\textbf{Hosted file}

\verb`Table 1.docx`  available at \url{https://authorea.com/users/403362/articles/528786-outcomes-of-pericardiectomy-for-constrictive-pericarditis-following-mediastinal-irradiation}

\textbf{Hosted file}

\verb`Table 2.docx`  available at \url{https://authorea.com/users/403362/articles/528786-outcomes-of-pericardiectomy-for-constrictive-pericarditis-following-mediastinal-irradiation}

\textbf{Hosted file}

\verb`Table 3.docx`  available at \url{https://authorea.com/users/403362/articles/528786-outcomes-of-pericardiectomy-for-constrictive-pericarditis-following-mediastinal-irradiation}

\textbf{Hosted file}

\verb`Table 4.docx`  available at \url{https://authorea.com/users/403362/articles/528786-outcomes-of-pericardiectomy-for-constrictive-pericarditis-following-mediastinal-irradiation}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

