PH Professional Network: 2015
Nightmares in Pediatric PH
Russel Hirsch, M.D.
Director , Pulmonary Hypertension Service
The Heart Institute
Cincinnati Children’s Hospital Medical
Center
Cincinnati, Ohio
Insert subject intotitle master
Patricia Lawrence, PNP
Pediatric Nurse Practitioner
Children’s Healthcare of Atlanta
Atlanta. Georgia
Disclosures
Dr. Russel Hirsch:
• Proctor, St. Jude Medical
• Off-label use of approved drugs
Patricia Lawrence:
• Research support from Eli Lilly
• Off-label use of approved drugs
This continuing education activity is managed and accredited by
Professional Education Services Group in cooperation with the
Pulmonary Hypertension Association. Neither PESG, nor PHA, nor
any accrediting organization support or endorse any product or
service mentioned in the is activity.
PESG and PHA staff has no financial interest to disclose.
Commercial Support was not received for this activity.
Learning Objectives
At the conclusion of this activity, the participant will be able to:
1. Recognize risks associated with PH therapy and how PH therapy can
be harmful in certain patient populations
2. Describe solutions for preventing medication errors in the outpatient
setting for patients on parenteral PH treatments
3. Discuss potential side effects that impact a patient’s quality of life
Overview
• Every diagnosis of Idiopathic PH in a child is a
nightmare
• Cases we will discuss will highlight:– Difficulties in diagnosis
– Complexity of management
– Adverse effects of medications
– Impact of sepsis
– Autonomy and ethical aspects in decision making
KH, 12 year old female
• Asymptomatic, normal activities– Competitive basketball player
• Cleaning horse stall and kicked in the belly
• ER evaluation with severe abdominal pain /
hematuria
• MRI– Renal contusion
– Multiple hepatic lesions (AVM vs. hepatic nodules)
– Dilated IVC
KH: Initial Evaluation
• No cardiac symptoms
• BP 132/60
• Sternal heave / Palpable 2nd heart sound
• Loud, wide split S2
• 3cm hepatomegaly, mild tenderness
KH: Baseline Studies
KH: Baseline Echo Images
KH: Baseline MRI Images
KH: Baseline CC
BL
30%
FiO2
iNO 80ppm /
FiO2 80%
Rp
(WU x m2)
9.1 9.8
Rs
(WU x m2)
13.5
CI
(l/min/m2)
5.4 3.68
Mean PA
Pressure
(mmHg)
52 50
Mean RA
Pressure
(mmHg)
7
KH: Course
• Open liver biopsy during cardiac catheterization,
and hepatic vein injections– Focal nodular hyperplasia with malignant potential
– Portal venous malformation with Abernathy-type physiology
KH: Course
• Medications commenced as out-patient– Oral Sildenafil
– Inhaled treprostinil• Dose increased gradually to maximum of 9 breaths q4h
• Initial occasional dizziness, but then well tolerated
– Bosentan contra-indicated
• At 3 months– Asymptomatic
– Compliant
– Liver transplant evaluation in progress• Parents somewhat reticent at this stage
KH: Follow-Up Cath: 5 Wks
BL
30%
FiO2
Follow-Up
(5 weeks)
Rp
(WU x m2)
9.1 4.95
Rs
(WU x m2)
13.5 11.73
CI
(l/min/m2)
5.4 5.45
Mean PA
Pressure
(mmHg)
52 42
Mean RA
Pressure
(mmHg)
7 7
KH: Follow-Up: 9mo
• No change in symptoms
• Echo Deterioration– RV dilated / function worse
– Increased TR Doppler jet velocity
– Increased septal flattening
• Deterioration in hepatic parameters– Albumin decreased
– GGT increased
– Ammonia increased
KH: Follow-Up Cath: 10mo
BL
30%
FiO2
Follow-Up
(5 weeks)
Follow-Up
(10 mo)
Rp
(WU x m2)
9.1 4.95 7.8
Rs
(WU x m2)
13.5 11.73 8.0
CI
(l/min/m2)
5.4 5.45 4.6
Mean PA
Pressure
(mmHg)
52 42 52
Mean RA
Pressure
(mmHg)
7 7 9
KH: Clinical Adjustments
• Broviac central line placed– After much family discussion
• Converted from inhaled to IV treprostinil– Titrated up to a dose of 23ng/kg/min at time of DC
• Considerable more discussion in regard to liver
transplantation
Survival: Portopulmonary Hypertension
• REVEAL Registry data*• 5 yr survival 40% in subjects with PoPH versus 64% IPAH/FPAH
• Review of Mayo Data (1994-2007)**• 74 PoPH patients
• No treatment (19 pts): 5 yr survival 14%
• Pulm Vaso-dilator (43 pts): 5 yr survival 45%
• Liver Transplantation***• mPAP > 50mmHg - 100% liver transplant mortality
• mPAP < 35mmHg – 100% liver transplant survival
* Krowka et.al. Chest 2012;141:906-915
**Swanson et.al. AmJTransplant 2008;8:2445-2453
***Krowka et.al.Liver Transpl 2000;6:443-450
On-Going ManagementBL
30%
FiO2
Follow-
Up
(5
weeks)
Follow-
Up
(10 mo)
Follow-
Up
14 mo)
Rp
(WU x
m2)
9.1 4.95 7.8 6.59
Rs
(WU x
m2)
13.5 11.73 8.0 12.44
CI
(l/min/m2)
5.4 5.45 4.6 5.3
Mean PA
Pressure
(mmHg)
52 42 52 49
Mean RA
Pressure
(mmHg)
7 7 9 9
On-Going Management
• Regular clinic visits
• Further up-titration to 54ng/kg/min
• Generally feeling well, no complaints
• Full-time at school
• Intense conversation re liver transplantation
On-Going Management
BL
30%
FiO2
Follow-
Up
(5
weeks)
Follow-
Up
(10 mo)
Follow-
Up
14 mo)
Follow-
Up
(18 mo)
Rp
(WU x m2)
9.1 4.95 7.8 6.59 6.1
Rs
(WU x m2)
13.5 11.73 8.0 12.44
CI
(l/min/m2)
5.4 5.45 4.6 5.3 6.1
Mean PA
Pressure
(mmHg)
52 42 52 49 51
Mean RA
Pressure
(mmHg)
7 7 9 9 9
Clinical Course
• Presented to local ER 4 weeks post cath– Low grade fever x 2 days
– Subtle loss of appetite
– Diagnosed with UTI, treated nitrofurantoin
– Fever resolved
• Called PH office 3 weeks later– 7.5Kg weight loss
– Intermittent diarrhea
– Malaise
– Febrile
Acute Presentation
• Unwell appearing
• Bloated
• Pale
• Febrile to 38.7°C
• Pulse 128/min
• BP 135/80
• RR 20/min
Acute Presentation
• Mild peripheral edema
• Hyperdynamic precordium
• Prominent sternal heave / palpable P2
• Loud S2 with, with wide split P2
• 3/6 holosystolic murmur at tricuspid area
• Liver unchanged / no ascites
• Clear lung fields
CXR
First Presentation Current Presentation
New Studies
New Study
First Presentation Current Presentation
New Studies
Presumed Diagnosis: Endocarditis
• Blood Cultures– Positive for Streptococcus Mitis (CVC as well as peripheral cultures)
• CRP: 10.9 (< 0.3)/ ESR: > 40
• CBC / chemistries / liver enzymes stable
• Mild increase in INR
Subsequent Course
• Commenced on Ceftriaxone
• Over course of 6 day stay– Initial mild clinical improvement
– Broviac removed / PICC line inserted once cultures negative
– Fever resolved
– Appetite initially improved, then deteriorated
• Just prior to discharge– Sleeping more
– Mild peripheral edema
– Further loss of appetite
– Echo deterioration
Echo Prior to Discharge
Options……
• Repair / replace the tricuspid valve– Almost certain RV failure with need for mechanical support
? Endpoint
• Repair / replace the tricuspid valve with
transition to Novalung? Endpoint
• Repair / replace the tricuspid valve with
transition to Novalung, and list for lung and liver
transplant
The Family’s Decision
• To go home…..– Neurologically and behaviorally intact teenager
– Previously perfectly well
– Curable PH with liver transplant with excellent prognosis
– No part in decision making
– Patient was not consulted
– Parents did not wish to have her informed of the issues or the prognosis
– Parents did not wish to have palliative care involved
Course
• Discharged on stable medications– IV Treprostinil 54ng/kg/min via PICC
– Sildenafil
– Lasix
– Antibiotics (to complete 6 week course)
– Analgesia
– Nasal cannula oxygen
• Over first 2-3 weeks– Shortness of breath
– Peripheral edema
– Bloated belly
– Intermittent chest pain
– Increased sleepiness and lethargy
Course
• Activities– Family road trip to Montreal
– Make-a-Wish to Hawaii to swim with dolphins• (needed to be supported in the water)
• Completed antibiotics 5 weeks post discharge
• Family decided to forgo follow-up appointment at
that time
………..then……
• 8 weeks post discharge, mother called to report
that she seemed to be doing better
Follow-Up Visit at 10 Weeks
• Felt well, no complaints
• Normal appetite
• No shortness of breath
• No further swelling of her legs or belly bloating
• No longer using supplemental O2
• No analgesia
• Wanted to go back to school
• Resumed riding her horse
Follow-Up Visit at 10 Weeks
• Exam:– P 90/min; BP 120/70; O2 Sat 100%
– Peripheries warm / normal pulses
– Quite precordium
– Mild prominence of the S2, with variable split
– Quiet 1/6 holosystolic murmur at the left upper sternal border
– Clear lung fields
– Soft belly; no masses
Follow-Up Echo
Follow Up Echo
Wow!!!!!!!
Where to from here….?
• Scheduled for cath…….rescheduled
• Maintained on same medication
• Credibility of care givers a major family issue
• Pathophysiology of her course is remarkable
• Teenager patient autonomy
Children’s Healthcare of Atlanta
Case #2
Children’s Healthcare of Atlanta
CS, a 10 year old male with
an unusual history
• Presented to our PH team in December 2012 after admission to PICU for hypoxia and shortness of breath
• Cardiology fellow saw patient night of admission
• “He’s had a normal echo in the past, but let’s just do another one”
• Echo findings led to PH inpatient consult
Children’s Healthcare of Atlanta
Chart review and detailed history
2011
Syncope
2/2011
Nl head CT
ref to
Cardiology
Normal
EKG & Echo
March
2011
Normal
exercise test
March 2011
2011
Syncope
2/2011
Nl head CT
ref to
Cardiology
Normal
EKG & Echo
March
2011
Syncope
4/25/2011
Borderline
QTc
-Cardiology
Consult-
Event
Syncope
4/30/2011
with event
monitor
Syncope
5/7/2011Tilt
table
Admission
Children’s Healthcare of Atlanta
Chart review and detailed history
• Referral and visits to Neurology on 5/2011 and
8/2011
• Exam and EEGs all suggestive of neurocardiogenic
syncope
• Felt to have ‘reactive autonomic nervous system’
2011
1
2
3
4
Syncope # 5
11/2011
Children’s Healthcare of Atlanta
Chart review and detailed history
• 2/2012 - Referral to endocrinology
– No endocrinologic explanations for syncopal episodes
2011 2012
5/2012 11/2012 Admission
5 Syncopal
Episodes
2011 2012
5/2012 11/2012
5 Syncopal
Episodes
12/7/12 Admission
Children’s Healthcare of Atlanta
CS meets the PH team after 12/7/12 admission
for hypoxia
Children’s Healthcare of Atlanta
CS meets the PH team after 12/7/12 admission
for hypoxia
Tests included:
• Walk test distance 378, desaturation to 85%
• PSG without OSA, + nocturnal hypoxemia
• Pulmonary Function Tests
Children’s Healthcare of Atlanta
12/2012 Admission
CXR
• CXR - interstitial lung
disease vs pulmonary
hemorrhage
Children’s Healthcare of Atlanta
12/2012 Admission
Chest CT
Children’s Healthcare of Atlanta
Abnormal vs Normal Chest CT
Children’s Healthcare of Atlanta
12/2012 Admission
Echocardiogram
Children’s Healthcare of Atlanta
PH “Crisis”
• After getting emotional & angry with parents after
learning he may not go home for a few days
Children’s Healthcare of Atlanta
12/2012 Admission
cardiac catheterization
Rest iNO + O2
CVP 11
mPAp 52
PVR 15.9 9.1
Wedge 10
CI
• Attempted bronch in cath lab, discontinued
• Extensive pruning of distal small branches
• Started on tadalafil with no evidence
of pulmonary edema
Rest iNO + O2
CVP 11 11
mPAp 52 43
PVR 15.9 9.1
Wedge 10 11
CI 2.6 3.5
Children’s Healthcare of Atlanta
Several PH “crises” at home
• 12/2012 and 1/2013 requiring short admissions
• Usually occurred after emotional outburst or activity
• Saturations would often dip to mid 70s
• lasix started, tadalafil stopped and restarted at smaller dose
Children’s Healthcare of Atlanta
Lung biopsy
• 1/29/2013- Confirmed
PVOD
– Arrest after
procedure requiring
intubation, pressors
– Pulse steroids started
Children’s Healthcare of Atlanta
Photos of lung surface
at time of biopsy
Children’s Healthcare of Atlanta
Photos of lung surface
at time of biopsy
Children’s Healthcare of Atlanta
Normal lung surface
Children’s Healthcare of Atlanta
Pulmonary Veno-occlusive Disease
Normal Abnormal
Children’s Healthcare of Atlanta
PVOD
• Overlap of PVOD and PCH
• Causes of PVOD unknown
• 5-10% of cases diagnosed with idiopathic PAH
• Wide age range but primarily in children and adults
• Median survival ~ 2 years from diagnosis
• Symptoms include cough, hypoxia and progressive
dyspnea
Children’s Healthcare of Atlanta
Pediatric PVOD – a retrospective analysis
Children’s Healthcare of Atlanta
PH clinic 4/2013
• Echo
• Walk test
• PH staff witnessed crisis immediately after walk
test
Children’s Healthcare of Atlanta
PH crisis in clinic after walk
• Sats to 70s
• HR to 140
• Flash pulmonary
edema with crackles
which resolved within
1 hour
Children’s Healthcare of Atlanta
Admission after PH crisis 4/2013
• Admission – started Imatinib
– PACT team consult
– Family not interested in lung transplant
– Hospice
– Patient not consulted about wishes (11 years old at time)
Children’s Healthcare of Atlanta
Imatinib for PVOD
Children’s Healthcare of Atlanta
Clinical improvement within weeks
CT one year later
Children’s Healthcare of Atlanta
Chest CT comparison
Children’s Healthcare of Atlanta
Echocardiogram at time of repeat Chest CT
Children’s Healthcare of Atlanta
Subsequent visits
• Stable echos
• Complaint of ‘breathing bothers me’
• Steroid weans
• Main complaint of abdominal pain
• Constipation
Children’s Healthcare of Atlanta
Interim Data
Red – TR jet
Gold –walk
Blue - BNP
Children’s Healthcare of Atlanta
Follow up cardiac catheterization
12/2012 1/2015
CVP 11 9
mPAp 52 48
PVR 15.9 11.7
Wedge 10 11
CI 2.6 3.14
-Increased tadalafil
-Later started calcium channel blocker
Children’s Healthcare of Atlanta
Subsequent visits
• Occasional complaints of chest pain and difficulty with
breathing but no change in vital signs, echo
• No syncopal episodes since 12/2012 since starting on
tadalafil
• No PH crises from 4/2013 when Imatinib started
• Patient not informed of diagnosis or prognosis
Children’s Healthcare of Atlanta
And then...a PH crisis
April 2015
• Increased CCB
• Another PACT team visit
• Steroid burst
Children’s Healthcare of Atlanta
PH clinic 7/22/15
• Seen for complaints of chest tightness, increased
oxygen requirement
• Echo stable
• BNP less than 10
• Normal physical exam with splitting of S2
• Long discussion about family’s wishes given ‘return’ of
PH crises
Children’s Healthcare of Atlanta
And then…..a syncopal episode
Admitted 8/13/15
Children’s Healthcare of Atlanta
Clinical Data
• BNP normal
• LFTs normal
• CXR improved 12 hours later
• O2 requirement returned to normal
Children’s Healthcare of Atlanta
Most recent clinical data
Red – BNP
Gold –TR jet
Blue - PVR
Children’s Healthcare of Atlanta
8/13/15 Admission for syncopal episode
• Family devastated by ‘return’ of syncope
• Imatinib increased
• Discontinued amlodipine
• Palliative care team involvement
• Discussions around lung transplant resumed
• Family shared diagnosis and prognosis with patient
Children’s Healthcare of Atlanta
Hot off the presses
• Clinic visit 9/16/15
• TR 120
• 6 minute walk distance 308
• BNP 70
• Admitted to restart amlodipine, monitor
• ? Intercurrent illness?
• Family has appointment with lung transplant center for
evaluation
Children’s Healthcare of Atlanta
What next?
• Additional PAH therapy?
• Atrial Septostomy?
• Lung transplant?
2011 2012 2013 2014 2015
5 Syncopal
Episodes
3 Syncopal
Episodes
1 Admit 4 Admits 5 Admits
1 Syncopal
Episode
1 Admit 3 Admit
Children’s Healthcare of Atlanta
Pulmonary Hypertension Team
at CHOA
• Amanda Brown, PNP
• Anna Burnett Gay, PNP
• Jeryl Huckaby, RRT
• Usama Kanaan, MD
• Nikhil Chanani, MD
• Dawn Simon, MD
Pulmonary Hypertension Team
at
CCHCM
• Michelle Cash
• Alison Cress
• Lisa Burns
• Jenna Faircloth
• Kathy Gosney
• Bill Nichols
• Katie Lutz
• Mike Pauciulo
• The nurses on A6C and
in the CICU and NICU
• Fellows who assist with
consultations
Children’s Healthcare of Atlanta
What questions do you have?
Children’s Healthcare of Atlanta
Obtaining CME/CE Credit
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