Corresponding Author:
Si Pham, MD, FACS
Department of Cardiothoracic Surgery,
Mayo Clinic Hospital
4500 San Pablo Rd.| Jacksonville, FL 32224.
Phone: 904-956-3212. Fax :904-956-8060 Email:
Pham.Si@mayo.edu
Word Count: 1500 (without references)
Conflict of Interests : None
Funding sources: None
Disclosure: None
Abstract.
The surgical treatment of pulmonary hypertension (PH), with or without
pulmonary artery aneurysm, has evolved during the last 40 years from
heart-lung transplants to bilateral lung transplants as the treatment of
choice for PH patients with preserved right and left ventricular
function and without complex cardiac abnomalies.
Pulmonary artery aneurysm (PAA) is a rare finding in general population,
first reported at Mayo Clinic by Deterling and Clagett in postmortem of
109,571 autopsies, only 8 cases were found with incidence being
0.007%.1 The majority of PAA cases (80%) occur in
the main pulmonary artery (PA), the rest beyond bifurcation with
aneurysms involving the left PA were more common than those of the right
PA.2 The definition of main PAA is still debatable.
Kreibich et al., suggested that a main PA with a diameter above 29
millimeters (mm) was considered aneurysmal.3 However,
Brown et al., suggested that PAA was defined as having a main PA
diameter exceeds 40 mm.4 Multiple etiologies of PAA
have been described, such as congenital, acquired, and idiopathic
etiologies. The most common congenital anomalies are persistent ductus
arteriosus, ventricular septal and atrial septal
defects.5,6 There is a wide range of acquired
etiologies for PAA, including infections with tuberculosis, syphilis or
other bacterial endocarditis, and septic embolisms.7-9Furthermore , a number of autoimmune and connective tissue disorders
have been implicated in causing PAA.10,11 Greene et
al., suggested 4 pathological and clinical criteria for an idiopathic
PAA: i) simple dilatation of the pulmonary trunk with or without
involvement of the rest of the arterial tree, ii) absence of
intracardiac or extracardiac shunts, iii) absence of chronic cardiac or
pulmonary disease, and iv) absence of arterial disease such as syphilis
or arteriosclerosis of the pulmonary vascular tree.12Pulmonary hypertension is an important causative and prognostic factor
for PAA and plays a critical role in treatment decision.
In this issue of the Journal of Cardiac Surgery,
Pelenghi et al., reported a
successful operation that includes bilateral lung transplant, pulmonary
artery aneurysmorrhaphy and
pulmonary valve replacement in a patient with severe idiopathic
pulmonary arterial hypertension complicated by giant pulmonary aneurysm,
pulmonary valve regurgitation and right ventricle
dysfunction.13 The patient was initially listed for
heart-lung transplantation, but because of the unavailability of a
heart-lung donor and clinical deterioration after 7 months on the
waiting list, the patient’s listing status was converted to bilateral
lung transplant. She underwent bilateral lung transplant (BLT), PA
aneurysmorrhaphy and open deployment of an injectable porcine pulmonic
valve (No-React® Injectable
BioPulmonic™ valves, Bio Integral
Surgical, Inc., Mississauga, ON, Canada) that was designed for
percutaneous deployment. Bilateral sequential lung transplant or en-bloc
double lung transplant, along with repair or replacement of pulmonary
artery and valve for patients with PAA and severe pulmonary
hypertension, have been previously reported.14-16However, this is the first reported case of using such a bioprosthesis
in this clinical scenario. The long-term outcome of this device, which
is prone to early failure (85% failure rate at 5.2 years), is
uncertain.17
Currently, there is no clear guideline for treating patients with PAA
because the rarity of the disease, and the paucity of data on its
natural history and long-term outcomes. Treatment options include close
observation, medical treatment, repair of the aneurysm, and in cases
associated with severe pulmonary hypertension, bilateral lung or
combined heart-lung transplantation. For patients with a low-pressure
PAA without left-to-right shunting, a more cautious approach may be
warranted.18,19In these patients, some authors recommended that the timing of surgical
intervention is dictated by changing of ventricular size and function,
and clinical symptoms, but not so much on the size of the aneurysm
because the incidence of rupture is low. 18,19However, Kreibich et al., recommended surgical repair in adults with
pulmonary trunk aneurysms >5.5 cm, similar to the
guidelines for aortic disease.3
If the signs of right ventricular dysfunction, or pulmonary valve
dysfunction start to appear, early surgical repair is recommended. In
low pressure isolated PAA, several surgical procedures have been
reported. Pulmonary
aneurysmorrhaphy is a relatively simple and not time-consuming however,
this procedure will result in high recurrent rate, especially in PAA
related to connective tissue disorders or congenital structural heart
diseases. Therefore, aneurysmectomy and replacing the pulmonary artery
with a vascular conduit is advised.20 Various types of
conduits have been described, including polytetrafluoroethylene or
dacron vascular grafts, aortic or pulmonary homografts, porcine aortic
xenografts, and bovine jugular vein graft.21,22
A more aggressive surgical approach has been advocated for patients with
PAA and pulmonary arterial hypertension because of the risk of
dissection and rupture.23,24 In cases of pulmonary
hypertension with preserved right and left ventricle function, bilateral
lung transplant is the preferred option, and the donor main PA can be
used to replace the recipient’s PA and pulmonary
trunk.14 If the donor PA is short, pulmonary trunk of
the recipient can be reconstructed with the donor’s aortic
arch.15
Many patients with PAA also present with pulmonary valve regurgitation
(PVR), resulting from annular dilatation due to the PAA or from other
independent etiologies.25,26 When the pulmonary valve
(PV) is competent, a valve-sparing technique should be performed,
whereas the valve is repaired or replaced if there is significant
deformity and regurgitation.27 In the case reported in
the current issue of the journal, Pelenghi et al., elected to replace
the PV by open deployment of an
injectable porcine pulmonic valve
(No-React® Injectable BioPulmonic™ valves) that was designed for
percutaneous deployment.13 The problem with this valve
is that it has very poor long-term outcome when deployed percutaneously
in pediatric patients due to either malposition or neointimal
proliferation. 17 It remains to be seen how this valve
performs in an adult patient on immunosuppression.
In years past heart-lung transplant (HLT) was the treatment of choice
for patients with severe pulmonary hypertension. The first successful
heart-lung transplant was performed on a patient with idiopathic
pulmonary hypertension on March 9, 1981.28 As the lung
transplantation field matures and because of the severe shortage of
heart-lung donors, bilateral lung transplant has replaced heart-lung
transplant as the primary treatment option for patients with pulmonary
hypertension and preserved right and left ventricular
function.29
In patients with high pressure PAA with poor RV or LV function or due to
complicated cardiac congenital abnormalities (Eisenmenger Syndrome; ES),
combined heart-lung transplantation is indicated. For patients with ES,
the choice between bilateral lung transplant and heart-lung transplant
depends on the anomalies and whether the lesion is surgically
correctable. Using the United Network for Organ Sharing (UNOS) database
Federico et al., analyzed the outcomes of patients with ES who underwent
thoracic transplantation from 1987 to 2018.16 During
the study period, 442 adults with ES underwent either bilateral lung
transplant (n=126) or heart lung transplant (n= 316). The long-term
survival was comparable between the two groups. However, subgroup
analyses showed that patients with
atrial septal defect (ASD) fared
better with BLT while those with ventricular septal defect (VSD) had
better survival following HLT.
In conclusion, the treatment of severe pulmonary arterial hypertension
has evolved over the last four decades to allow for more expanded
selection criteria in the recipients, and utilization of different
ingenious modifications to deal with abnormalities of the pulmonary
artery and valve. It has been well documented that, in appropriately
selected patients, bilateral lung transplant is the treatment of choice
for those with severe pulmonary hypertension. The question that remains
is what to do with the pulmonary arterial aneurysm and pulmonary valve
regurgitation. Should the aneurysm be repaired with aneurysmorraphy and
risk high recurrence or should it be replaced, and if replaced, with
what material? Similarly, should a morphologically normal valve that has
regurgitation because of annular dilatation be repaired or replaced, and
if replaced, with what valve type? The case described in this issue of
the journal by Pelenghi et al., and other published reports do not
provide us with satisfactory answers, and we may not have these answers
any time soon because of the rarity of the condition. But we are
confident that as more cases are studied and followed longitudinally, we
will be able to provide better recommendations for our patients. The
first successful heart-lung transplant as a treatment pulmonary
hypertension was a true “paradigm shift”, or a “revolution”. From
this “revolution” the surgical treatment for patients with severe
pulmonary hypertension, with or without PAA, has evolved to include
either bilateral lung or heart-lung transplantation as the appropriate
treatment for each individual patient.
Author contributions Concept/design: SJ, BS, SMP. Drafting article: SJ; Critical revision of
article: ANP, BS, SMP; Approval of article: SJ, ANP, BS, SMP.