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

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

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

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 52 42 52 Pressure Mean RA 7 7 9 Pressure 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 52 42 52 37 Pressure Mean RA 7 7 9 7 Pressure 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