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 (~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
colleagues18, and a median of 11 years (range 2 to 30
years) as reported by Bertog and colleagues.11 Ling et
al reported a median range of 13 years7, and McCaughan
et al reported a range of 15 months to 44 years.19This may also reflect improved cancer cure rates, which have resulted in
greater longevity and thus the likelihood of developing delayed
cardiovascular sequelae.7 In previous studies,
lymphomas have been the most common malignancy for which mediastinal
radiation was received, followed by breast cancer.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.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.21 Brosius and
colleagues found interstitial myocardial fibrosis in patients who had
received prior irradiation.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.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.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.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.13
Mediastinal irradiation damages the vascular endothelium and leads to
radiation-induced vascular disease of peripheral, coronary and carotid
arteries.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.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.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%.13 Bertog
and colleagues also reported an operative mortality of 21% in this
subset of patients in their large series on pericardiectomy for
constriction.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.10However, 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.10The 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.