Title: Chronic Thromboembolic Pulmonary Hypertension Successfully
Treated in a Six Year Old with Asthma
Authors: Ryan M Serrano MD1, Greg S Montgomery
MD2, Tisha D Kivett BSN, RN3, Rohit
P Rao MD4, Michael W Johansen DO1
Affiliations
- Department of Pediatrics, Division of Pediatric Cardiology, Indiana
University School of Medicine, Riley Hospital for Children at Indiana
University Health, Indianapolis, Indiana.
- Section of Pediatric Pulmonology, Critical Care and Allergy,
PICU/Riley Hospital for Children, Indianapolis, Indiana.
- Pediatric Pulmonary Hypertension, Riley Hospital for children at
Indiana University Health
- Department of Pediatrics, Division of Pediatric Cardiology, University
of California San Diego, Rady Children’s Hospital, San Diego, CA.
Grants/Financial Support: None
Meetings: Presented at the 13th International
Conference Neonatal and Childhood Pulmonary Vascular Disease
Correspondence:
Ryan M Serrano
705 Riley Hospital Drive, RR 1134B
Indianapolis, IN 46202
317.274.2984 tel
317.944.9330 fax
ryserran@iupui.edu
Keywords: CTEPH, pulmonary hypertension, pulmonary thromboendarterectomy
Abbreviated title: CTEPH in a six year old with asthma
Introduction:
Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized
by incomplete resolution of pulmonary thromboemboli and the subsequent
development of pulmonary hypertension (PH). In adults, it is estimated
to occur in 0.5% to 3% of acute pulmonary embolism
survivors1, and in children is even less common. We
present a case of the youngest known patient in the United States to
have undergone successful pulmonary thromboendarterectomy (PTE) and
review the literature on diagnosis and management of this rare
condition.
Case Report
Our patient was a 6-year-old male with a history of moderate persistent
asthma and a remote history of multiple unprovoked deep vein thromboses
(DVTs), for which a thorough hypercoagulability work up had been
performed and was found to be normal. After initial treatment for his
DVTs, he was maintained on chronic prophylactic subcutaneous heparin
injections. Prior to acute presentation, he was seen twice in a general
pediatric pulmonary clinic for several months of worsening exertional
dyspnea that was attributed to poor medication adherence to his
prescribed asthma medications. He was in his usual state of health and
visiting relatives on the day he presented to an out-of-state emergency
department with syncope.
In the emergency department, a chest X-ray suggested cardiomegaly and
prompted an echocardiogram that showed severe pulmonary hypertension
based on a moderately dilated right ventricle with severely decreased
function, dilated pulmonary arteries, and an interventricular septum
that bowed in to the left ventricle. His pulmonary regurgitation Doppler
estimated an end diastolic pulmonary artery pressure of 30 to 40 mmHg.
Clinically, he was dyspneic but with clear lung sounds; he required 3
liters of nasal cannula oxygen to achieve normal oxygen saturations.
Upon transfer to our facility for further expert evaluation and
management of severe pulmonary hypertension, cardiac catheterization
hemodynamics confirmed the diagnosis of PH with mean pulmonary artery
pressures >40mmHg and a pulmonary vascular resistance index
of 8.83 Units x m2 (Figure 1). A ventilation-perfusion
scan showed multiple mismatched perfusion defects involving both right
and left lungs, suspicious for chronic thromboembolism. Computed
tomography (CT) of the chest showed right lower lobe subsegmental
pulmonary thrombus, confirming the diagnosis of CTEPH.
Given his worrisome clinical presentation with acute syncope and the
severity of his right ventricular dysfunction, he was started on triple
therapy including subcutaneous treprostinil, a selective
phosphodiesterase inhibitor, and an endothelin receptor antagonist. His
case was promptly reviewed by the multidisciplinary team of CTEPH
experts at UC San Diego and he was deemed a candidate for surgical PTE.
Within 4 weeks of presentation, he was transferred to San Diego and
underwent bilateral PTE with resection of level 2 to 3 disease (Figure
2) via the surgical technique described in prior
reports2. He was weaned off all PH therapy while in
the operating room in an effort to avoid reperfusion pulmonary edema, a
well-known complication of PTE. Repeat ventilation-perfusion scan prior
to discharge showed significant improvement with symmetric perfusion in
both lung fields. After returning home, an evaluation 4 months
post-surgery exhibited a clinically asymptomatic boy and an
echocardiogram with normal RV size and function without any signs of PH.
A pulmonary function test was also repeated and confirmed the prior
diagnosis of asthma, showing mild obstruction with reduced forced
expiratory volume/forced vital capacity ratio and notable scoop to the
flow-volume curve and expiratory flows were found to significantly
improve after bronchodilator administration. He continues to be followed
by hematology and is maintained on warfarin for anticoagulation with a
goal INR of 2 to 3.
Discussion
CTEPH is a rare, although possibly underdiagnosed, entity seen in all
age groups. Symptoms can be subtle and non-specific, making the
diagnosis challenging in the presence of other underlying conditions
such as asthma and the prognosis poor if severe pulmonary hypertension
and right ventricular dysfunction are present. While PH-targeted
therapies are often used, riociguat is the only FDA approved therapy for
inoperable disease in adults. The greatest chance for long term survival
is surgical PTE, with the lowest mortality and best immediate surgical
results at the highest volume centers such as UC San
Diego3.
As is common for many patients with CTEPH, our patient’s non-specific
symptoms mimicked a more common and more likely diagnosis of chronic
asthma, and he went undiagnosed for several months despite having
recurrent lower extremity thromboses–a known risk factor for the
development of CTEPH–and multiple physician encounters in the
outpatient and emergency room settings. While a normal
ventilation-perfusion scan makes the diagnosis of CTEPH unlikely, an
abnormal study warrants additional images via angiography or CT to
confirm or exclude the diagnosis of CTEPH and aid in surgical planning.
It has been suggested that for patients with operable CTEPH, medical
optimization with PH-targeted therapy to improve hemodynamics can unduly
delay potentially curable surgical treatment,4 however
we were able to stabilize our patient with triple PH-targeted therapy
without delaying the referral and transfer process to a center who could
confirm our diagnosis and perform PTE. Clearly, for our patient,
prophylactic subcutaneous heparin was not adequate anti-coagulation to
prevent recurrent thromboemboli, and a recent study in adults with CTEPH
suggests lower risk of recurrent venous thromboemboli in those patients
receiving vitamin K antagonists.5
In conclusion, our patient is the youngest reported case of surgically
treated CTEPH in the United States. Providers must maintain a high index
of suspicion for at risk patients with unexplained dyspnea to allow for
prompt diagnosis and evaluation for surgical treatment.
Even if right ventricular dysfunction and severe pulmonary hypertension
are present, surgical pulmonary endarterectomy can be performed
successfully in young patients.
References
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