A 12 Year Old with Liver Disease and Pulmonary Hypertension Russel - - PowerPoint PPT Presentation

A 12 Year Old with Liver Disease and Pulmonary Hypertension

Russel Hirsch, M.D. The Heart Institute Cincinnati Children’s Hospital Medical Center

X X X X X X X X

• Unanticipated consequences
• Ethical dilemmas
• Issues of autonomy
• Family / Care team trust issue
• Multi-system complexity
• Extreme resource allocation
• Logistic considerations
• Unfortunate outcomes
• ? Paternalism

KH, 12 year old female

Clinical Presentation

• Asymptomatic, normal activities

– Competitive basketball player / Horse (barrel) racing

• 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

• No cardiac symptoms

Examination

• BP132/60
• Classic signs of RVH and PH

– Sternal heave / Palpable 2nd heart sound, Loud, wide split S2

• 3cm hepatomegaly, mild tenderness

KH: Baseline Studies

KH: Baseline Echo Images

KH: Baseline Echo Images

KH: Baseline MRI Images

KH: Baseline CC

BL 30% FiO2 iNO 80ppm / FiO2 80% Rp 9.1 9.8 Rs 13.5 CI 5.4 3.68 Mean PA Pressure 52 50 Mean RA Pressure 7

KH: Course

• Open liver biopsy during cardiac

catheterization, and hepatic vein injections

– Focal nodular hyperplasia

High likelihood of malignant potential

– Portal venous malformation with Abernathy- type physiology

Family Discussion

• Offered liver transplantation

– Declined

• Agreed to commence vaso-dilator therapy

to maintain a transplantable state

– Plan for frequent reassessment

KH: Course

• Medications commenced as out-patient

– Oral Sildenafil – Inhaled treprostinil

• Dose increased gradually to maximum of 9 breaths q4h
• Occasional dizziness

– Bosentan contra-indicated

• Exercise restriction

Follow-Up at 3 Months

• Asymptomatic
• Compliant
• Liver transplant evaluation in progress

– Family reticent

KH: Follow-Up Cath: 3 months

BL 30% FiO2 iNO 80ppm / FiO2 80% Follow-Up (3 months) Rp 9.1 9.8 4.95 Rs 13.5 11.73 CI 5.4 3.68 5.45 Mean PA Pressure 52 50 42 Mean RA Pressure 7 7

Continued Follow-Up

• Maintained on Sildenafil and inhaled

treprostinil

• Active / asymptomatic
• Repeat cath 5 months post presentation,

continued stability

• 9 months post presentation

– Mild peripheral edema – Exertional dyspnea – Low Albumin

BL 3 months 9 month Rp 9.1 4.95 7.7 Rs 13.5 11.73 14 CI 5.4 5.4 4.9 Mean PA Pressure 52 42 52 Mean RA Pressure 7 7 9

Sildenafil and Inhaled Treprostinil

Therapeutic Intervention

• Tunneled central line placed from right subclavian vein

into the SVC

• Converted from inhaled to continuous IV treprostinil
• No further discussion about liver transplantation
• Gradual up-titration of treprostinil as out-patient
• Follow-Up Cath at 7 month after conversion to IV therapy

– No change in PA pressures or Rp despite substantial up-titration

Clinical Change:

18 months post presentation (2 months after last cath)

• One month history

– Low grade fever – 6kg weight loss – Intermittent nausea / occasional vomiting

• Exam

– Lethargic – Swollen / edematous – Harsh 3/ holosystolic murmur

Blood Cultures: Positive for Streptococcus mitis

• Severe TR
• Estimated RV pressure 95mmHg by TR Doppler velocity

• Severe TR
• Estimated RV pressure 95mmHg by TR Doppler velocity

• Severe TR
• Estimated RV pressure 95mmHg by TR Doppler velocity

Clinical Dilemma

• Active endocarditis / severe TR / Severe

CHF / Severe PH

– Unlikely to survive surgery without mechanical support

• No longer liver transplantable

– Severe PH

……….unless…..

“Only” way out

• Perform tricuspid valve replacement
• Support with ECMO / conversion to Lung

Assist Device

• List for lung and liver transplantation

………..family declined, and requested discharge as soon as possible….

Hospital Course

• Broviac removed

– PICC inserted

• D/C on antibiotics / Lasix / Continued

Remodulin

• Hospice contacted and involved

Out-Patient Course

• Slow decline

– Moderate facial and peripheral edema – Sedentary

• Blood culture negative at 6 weeks and d/c antibiotics

Clinic Visit at 3 months

• Persistent edema
• Comfortable
• Exercise capacity stable
• No echo / persistent clinical signs of PH

Clinic visit at 6 months

• Remarkably better!!!
• Active, back at school full-time
• No edema
• Signs of PH minimal
• Echo

– Severe TR with dilated RA – Estimated RV pressure 40-50mmHg

Conversion to Oral Treprostinil

• 10 months post endocarditis
• PICC line removed
• Cath with stable hemodynamics

– Lower CI – Higher SVR

BL 5 week 9 month 39 months Rp 9.1 4.95 7.7 6.2 Rs 13.5 11.73 14 23 CI 5.4 5.4 4.9 3.2 Mean PA Pressure 52 42 52 37 Mean RA Pressure 7 7 9 7 Parents still declined any further aggressive therapies, and no discussion of organ transplantation

Clinic Follow-Up – 4 months later

• Poor appetite
• Occasional vomiting
• Intermittent belly pain
• Cardiac exam: Unchanged / Edematous
• Large, tender mobile mass in the

epigastrium

• Echo with worse PH
• MRI of the belly…….

KH: Baseline MRI Images

• Massive enlargement of liver masses /

sub-capsular position

• Heterogeneous consistency
• Unclear if malignant conversion

Subsequent Course

• 6 months later, after horse race

– Severe belly pain

• ER evaluation with distended and acute

abdomen, clinically in shock

• Resuscitated and CT with free fluid (blood)

in abdomen

• Expired 2 hours later

Care for this patient:

It takes a village (and a hospital)!

• Cath Lab and Cath Lab Recovery (8 caths)
• Echo lab (31 studies)
• PH Service

– Michelle Cash, Melissa Magness, Susan Hoelle

• CICU / In-patient Cardiology Service
• Liver Service
• Infectious Disease Service
• Ethics Service
• Radiology (4 MRI’s / 1 CT / Uncountable CXR’s)
• Lab (29 CBC / 33 renal panels, etc.etc.)

Most Importantly……..

• Complexity of care

– Family demands – Religious and social influences – Ethical considerations – Resource allocation …….in addition to the medical issues

Thank You!

Portal Pulmonary Hypertension – Possible Mechanisms

• Imbalance of vasoconstrictive and vasodilatory

mediators

– Serotoinin, interlekin-1, endothelin -1, glucagon, secretin, thromboxane B2, etc.

• Genetic predisposition
• Thromboembolism from the portal venous

circulation

• Hyperdynamic pulmonary circulation
• Inflammation

– Elevated cytokines in cirrhosis

Survival: Portal Pulmonary 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