PULMONARY PULMONARY HYPERTENSIONHYPERTENSION

UPDATEUPDATE

Dianne L. Zwicke, MDDianne L. Zwicke, MDClinical Associate Professor of MedicineClinical Associate Professor of Medicine

University of Wisconsin School of Medicine and Public University of Wisconsin School of Medicine and Public HealthHealth

Milwaukee Clinical CampusMilwaukee Clinical Campus Milwaukee, WisconsinMilwaukee, Wisconsin

FINANCIAL DISCLOSUREFINANCIAL DISCLOSURE

Dianne L. Zwicke, MDDianne L. Zwicke, MD I have been an investigator and received study grants from the following I have been an investigator and received study grants from the following

companies: companies:

Glaxo – Welcome Glaxo – Welcome *United Therapeutics *United Therapeutics *Pfizer *PfizerMedtronic Medtronic

MyogenMyogen Encysive Encysive Co Therix Co Therix IkariaIkaria

PRE-DIX PRE-DIX *Gilead *Gilead Actileon Actileon NovartisNovartis

Lilly Lilly Bayer Bayer GENO GENO

* Participated in Advisory Boards* Participated in Advisory Boards

Dianne L. Zwicke, MD

PULMONARY HYPERTENSIONPULMONARY HYPERTENSION

Vascular (PAH)Vascular (PAH) Non-VascularNon-Vascular MixedMixed

IdiopathicIdiopathic COPDCOPD Congenital Congenital

Collagen VascularCollagen Vascular OSAOSA ? COPD ? COPD

Sickle CellSickle Cell ILDILD ? ILD ? ILD

HIVHIV PEPE ? PE ? PE

HepatopulmonaryHepatopulmonary RestrictiveRestrictive

Clinical Classification: Where Is the Clinical Classification: Where Is the Lesion?Lesion?

ALK-1, activin receptor-like kinase 1; Ao, aorta; BMPR2, bone morphogenetic receptor type 2; HHT, hereditary ALK-1, activin receptor-like kinase 1; Ao, aorta; BMPR2, bone morphogenetic receptor type 2; HHT, hereditary hemorrhagic telangiectasia; HIV, human immunodeficiency virus; LA, left atrium; LV, left ventricle; PA, pulmonary hemorrhagic telangiectasia; HIV, human immunodeficiency virus; LA, left atrium; LV, left ventricle; PA, pulmonary artery; PC, pulmonary capillary bed; PV, pulmonary vein; RA, right atrium; RV, right ventricle; VC, vena cava.artery; PC, pulmonary capillary bed; PV, pulmonary vein; RA, right atrium; RV, right ventricle; VC, vena cava.Simonneau et al. Simonneau et al. J Am Coll CardiolJ Am Coll Cardiol. 2009;54(1 suppl S):S43-S54.. 2009;54(1 suppl S):S43-S54.

VC RA RV PA PC PV LA LV Ao

Graphic adapted from http://cme.medscape.com/viewarticle/530730.

PULMONARY ARTERIAL HYPERTENSIONPULMONARY ARTERIAL HYPERTENSION

►Mean PA pressure > 24 mmHgMean PA pressure > 24 mmHg

►PCWP PCWP << 15mmHg 15mmHg

►PVR > 2.5 / 3.0PVR > 2.5 / 3.0

PATHOLOGIC CHANGESPATHOLOGIC CHANGESVascular PHVascular PH

►Smooth muscle hypertrophySmooth muscle hypertrophy► Intimal hyperplasiaIntimal hyperplasia► In situ thrombosisIn situ thrombosis►ArteritisArteritis►Plexogenic lesionPlexogenic lesion

PULMONARY HYPERTENSION PULMONARY HYPERTENSION Severity by Mean PAPSeverity by Mean PAP

26-35 Mild 26-35 Mild

36-45 Moderate36-45 Moderate

46-55 Severe46-55 Severe

> 55 Systemic> 55 Systemic

Epidemiology of PAH (WHO Group 1)Epidemiology of PAH (WHO Group 1)11

► Prevalence of PAH in associated Prevalence of PAH in associated conditions:conditions:

CTDCTDaa: 8%-12%: 8%-12%2,32,3

CHD: 15%-30%CHD: 15%-30%44

PoPH: 2%-6%PoPH: 2%-6%5,65,6

HIV: 0.5%HIV: 0.5%77

CHD, congenital heart disease; CTD, connective tissue disease; FPAH, familial pulmonary arterial hypertension; HIV, human immunodeficiency virus; IPAH, idiopathic pulmonary arterial CHD, congenital heart disease; CTD, connective tissue disease; FPAH, familial pulmonary arterial hypertension; HIV, human immunodeficiency virus; IPAH, idiopathic pulmonary arterial hypertension; PoPH, portopulmonary hypertension.hypertension; PoPH, portopulmonary hypertension.

1.1. Simonneau et al. Simonneau et al. J Am Coll CardiolJ Am Coll Cardiol. 2009;54(1 suppl S):S43-S54. . 2009;54(1 suppl S):S43-S54. 2. 2. Hachulla et al. Hachulla et al. Arthritis RheumArthritis Rheum. 2009;60:1831-1839. . 2009;60:1831-1839. 3.3. Mukerjee et al. Mukerjee et al. Ann Rheum DisAnn Rheum Dis. 2003;62:1088-1093. . 2003;62:1088-1093. 4.4. Landzberg. Landzberg. Clin Chest MedClin Chest Med. 2007;28:243-253. . 2007;28:243-253. 5.5. Hadengue et al. Hadengue et al. GastroenterologyGastroenterology. 1991;100:520-528. . 1991;100:520-528. 6.6. Krowka et al. Krowka et al. HepatologyHepatology. 2006;44:1502-1510. . 2006;44:1502-1510. 7.7. Sitbon et al. Sitbon et al. Am J Respir Crit Care Am J Respir Crit Care MedMed. 2008;177:108-113. . 2008;177:108-113. 8.8. Humbert et al. Humbert et al. Am J Respir Crit Care MedAm J Respir Crit Care Med. 2006;173:1023-1030.. 2006;173:1023-1030.

IPAH

>1 Risk factorAppetite suppressant

HIV

FPAHCTD

CHD

PoPH

Distribution of PAH in French Registry8

a Systemic sclerosis.

VASCULAR PH EPIDEMIOLOGYVASCULAR PH EPIDEMIOLOGY

► IdiopathicIdiopathic 1/500,000 1/500,000► Idiopathic (Necropsy) 750/500,000Idiopathic (Necropsy) 750/500,000► Idiopathic (Familial) 191/1926Idiopathic (Familial) 191/1926► Connective TissueConnective Tissue 1-100/1000 1-100/1000► HIVHIV 5/100 5/100► HepatopulmonaryHepatopulmonary 5-8/100 5-8/100► Anorexic drugAnorexic drug 12- 12-

25/500,00025/500,000

1-Year Mortality Remains High in FC IV 1-Year Mortality Remains High in FC IV PatientsPatients1,21,2

FC, functional class; QuERI, Quality Enhancement Research Initiative; WHO, FC, functional class; QuERI, Quality Enhancement Research Initiative; WHO, World Health Organization.World Health Organization.

1. 1. McLaughlin et al. McLaughlin et al. Am J Respir Crit Care MedAm J Respir Crit Care Med. 2009;179:A1043. . 2009;179:A1043. 2. 2. Mathier et al. Mathier et al. Am J Respir Crit Care MedAm J Respir Crit Care Med. 2009;179:A2658.. 2009;179:A2658.

9

29

46

0

10

20

30

40

50

II III IV

WHO FC

1-Y

ear

mo

rtal

ity

(%)

N=782

<30% on prostanoid

PULMONARY HYPERTENSION PULMONARY HYPERTENSION RIGHT HEART FAILURE SYMPTOMSRIGHT HEART FAILURE SYMPTOMS

► DOE - 2 Years - 70%DOE - 2 Years - 70%

► CP - RV ischemia - 30%CP - RV ischemia - 30%

► Syncope / near syncope – 30%Syncope / near syncope – 30%

► Fatigue - 90%Fatigue - 90%

► Raynauds phenomonon – 10%Raynauds phenomonon – 10%

► Ascites - 20%Ascites - 20%

► Peripheral edema - Peripheral edema - 10%10%

► Early satiety - 50%Early satiety - 50%

► Hoarseness - 10%Hoarseness - 10%

PULMONARY HYPERTENSIONPULMONARY HYPERTENSIONDiagnostics - BasicsDiagnostics - Basics

► History & PhysicalHistory & Physical► Labs- CBC, CMP, TSH, ANA, RF, CRP, Labs- CBC, CMP, TSH, ANA, RF, CRP,

ESR, HIV, ANTICARDIOLIPIN ABESR, HIV, ANTICARDIOLIPIN AB► EKG, CXREKG, CXR► Full PFT’SFull PFT’S► Lung scanLung scan► Echo with contrast / TEEEcho with contrast / TEE

PULMONARY HYPERTENSION PULMONARY HYPERTENSION Diagnostics - AdvancedDiagnostics - Advanced

► HR Chest CTHR Chest CT► Pulmonary AngiographyPulmonary Angiography► Sleep study / screenSleep study / screen► 6 minute walk6 minute walk► Cardiac cath with pharmacologic Cardiac cath with pharmacologic

challenge -- LAST STUDY!challenge -- LAST STUDY!

Hemodynamic Progression of PAHHemodynamic Progression of PAH

CO, cardiac output; PAP, pulmonary arterial pressure; PVR, CO, cardiac output; PAP, pulmonary arterial pressure; PVR, pulmonary vascular resistance; RAP, right atrial pressure.pulmonary vascular resistance; RAP, right atrial pressure.

Time

PAPPVRRAPRAP

CO

Pre-symptomatic/ Compensated

Symptomatic/ Decompensating

Symptom Threshold

Right Heart Dysfunction

Declining/ Decompensated

Symptoms

Nitric oxidedeficiency

Endothelinoverexpression

Prostacyclindeficiency

ERAsBlock the binding of ET-1 to its receptors, preventing vasoconstrictor effects of ET-13

PDE-5 inhibitorsBlock the activity of PDE-5, restoring vasodilation through an increase in cGMP1

ProstacyclinSupplement the deficiency in PGI2, resulting in vasodilation and inhibition of platelet aggregation2

THERAPIES

ABNORMALITIES

Vasoactive Mediators Involved In Vasoactive Mediators Involved In PAHPAH

cGMP, cyclic guanosine monophosphate; ERA, endothelin receptor antagonist; ET-1, endothelin; PDE-5, phosphodiesterase type 5; PGIcGMP, cyclic guanosine monophosphate; ERA, endothelin receptor antagonist; ET-1, endothelin; PDE-5, phosphodiesterase type 5; PGI22, prostacyclin., prostacyclin.

1. 1. Humbert et al. Humbert et al. J Am Coll CardiolJ Am Coll Cardiol. 2004;43(suppl S):13S-24S. . 2004;43(suppl S):13S-24S. 2. 2. Humbert et al.Humbert et al. N Engl J Med N Engl J Med. 2004;351:1425-1436. . 2004;351:1425-1436. 3. 3. Galiè et al. Galiè et al. Eur Heart JEur Heart J. 2004;25:2243-2278. 2004;25:2243-2278..

Overall PAH Therapy Use in Enrolled PopulationOverall PAH Therapy Use in Enrolled Population1,21,2

ERA, endothelin receptor antagonist; PDE-5I, phosphodiesterase type 5 inhibitor; QuERI, Quality Enhancement Research Initiative.ERA, endothelin receptor antagonist; PDE-5I, phosphodiesterase type 5 inhibitor; QuERI, Quality Enhancement Research Initiative.

1. 1. McLaughlin et al. McLaughlin et al. Am J Respir Crit Care MedAm J Respir Crit Care Med. 2009;179:A1043. . 2009;179:A1043. 2. 2. Mathier et al. Mathier et al. Am J Respir Crit Care MedAm J Respir Crit Care Med. 2009;179:A2658.. 2009;179:A2658.

28

43

2522

0

10

20

30

40

50

PDE-5I ERA ProstanoidCombination

Pa

tie

nts

(%

)

N=782

HPAH, hereditary pulmonary arterial hypertension; IPAH, idiopathic pulmonary arterial hypertension; IV, intravenous; NS, not significant; PGI2, prostacyclin; Tx, treatment.

Sitbon et al. Slides presented at European Respiratory Society; September 16-18, 2007; Stockholm, Sweden.

Has Survival Meaningfully Improved Has Survival Meaningfully Improved

With Modern Therapies?With Modern Therapies?

0 12 24 36 48 60

n=269

n=260

n=118

Before 1992 (no specific Tx)

1992-1999 (only IV PGI2)

After 2000 (current therapies)

NS

P<0.05, log-rank test

Months0

25

50

Su

rviv

al (

%)

75

100IPAH, HPAH, and anorexigen-associated PAH

PULMONARY ARTERIAL PULMONARY ARTERIAL HYPERTENSIONHYPERTENSION

MEDICALMEDICALTHERAPIESTHERAPIES

EPOPROSTINIL (Flolan, EPOPROSTINIL (Flolan, Veletri)Veletri)

► ProstacyclinProstacyclin

► 75% sustained 75% sustained in PVR in PVR

► 10% are non responders10% are non responders

► Double lumen catheterDouble lumen catheter

► Requires continuous infusionRequires continuous infusion

BOSENTAN (Tracleer)BOSENTAN (Tracleer)► ET – 1 antagonistET – 1 antagonist

► Binds ETBinds ETAA – ET – ETBB receptors in endothelium and vascular receptors in endothelium and vascular smooth musclesmooth muscle

► P450 pathway (2C9, 3A4)P450 pathway (2C9, 3A4)

► 3-5 hour max plasma concentration3-5 hour max plasma concentration

► t½ is five hourst½ is five hours

► 95% bound to albumin, excreted in bile95% bound to albumin, excreted in bile

► 62.5 – 125 mg bid orally, 1-2 month Rx62.5 – 125 mg bid orally, 1-2 month Rx

TREPROSTINIL (Remodulin)TREPROSTINIL (Remodulin)

►UT – 15UT – 15

►Prostacyclin analogueProstacyclin analogue

►SQ or IV infusionSQ or IV infusion

►Modified insulin pump – SQModified insulin pump – SQ

INHALED NITRIC OXIDEINHALED NITRIC OXIDE

►Endothelial derived relaxing factorEndothelial derived relaxing factor

►Endogenous mediator for smooth Endogenous mediator for smooth muscle relaxationmuscle relaxation

►Selective pulmonary vasodilator Selective pulmonary vasodilator through cGMP pathwaythrough cGMP pathway

► Increases oxygenationIncreases oxygenation

SILDENAFIL (RevatioSILDENAFIL (Revatio))

► PDE – 5 InhibitorPDE – 5 Inhibitor

► Found abundantly in pulmonary vasculatureFound abundantly in pulmonary vasculature

► Inhibits proliferationInhibits proliferation

► Potent pulmonary vasodilationPotent pulmonary vasodilation

► Increased epistaxis and GI bleedIncreased epistaxis and GI bleed

► Can’t prescribe nitratesCan’t prescribe nitrates

ILOPROST (Ventavis)ILOPROST (Ventavis)

► Inhaled prostacyclin derivativeInhaled prostacyclin derivative

► 6-9 treatments/day6-9 treatments/day

► 10-15 minutes/treatment10-15 minutes/treatment

► Mini NebulizerMini Nebulizer

AMBRISENTAN (LetairisAMBRISENTAN (Letairis))

► Endothelin receptor blockerEndothelin receptor blocker

► WHO group 1-3, WHO class 2 or 3 symptomsWHO group 1-3, WHO class 2 or 3 symptoms

► 5 or 10mg daily, tablet5 or 10mg daily, tablet

► IPH, CTD, HIV, diet drugsIPH, CTD, HIV, diet drugs

► Caution=pregnancy; liver toxicity (Label Caution=pregnancy; liver toxicity (Label removed)removed)

INHALED EPOPROSTINIL (Flolan)INHALED EPOPROSTINIL (Flolan)

► 30-80ng / kg / min30-80ng / kg / min

► Special delivery Special delivery systemsystem

Study Data

Methods

SET UPIntroduction

CLINICAL IMPLICATION

Based on this preliminary subset population analysis, inhaled epoprostenol may be efficacious in wider clinical settings for patients with pulmonary artery hypertension. It is more cost effective. Further studies are warranted to guide therapy in other clinical subsets of patients.

The selected study population was patients undergoing cardiothoracic surgery, at St Lukes Medical Center, in Milwaukee, Wisconsin, between July 2008 and April 2009. Anesthesiologists prospectively initiated inhaled EPO therapy, using the AccuNeb, on the vasodilated and fully anesthetized patients, with a measured PA systolic pressure greater than 60mmHg by Swan-Ganz catheter. We collected data by chart review of the identified study population. Pulmonary artery pressure and cardiac index were compared using two sample paired t-test, respectively (two-tailed).

ConclusionInhaled Epoprostenol demonstrated excellent clinical and hemodynamic results and was well tolerated in this critically ill subgroup of patients. It was a cost effective alternative to inhaled nitric oxide with a net savings more than $875,000 .

Dianne Zwicke MD, Krishna Nagendran MD, Faisal Hayat MD, Theodore Gronski MD, Jonathan Kay MD, Frank SpexarthRPH, Wende Moline NP, Andrea Krause NP, Mori Naoyo PHD

Figure 2. Sulfur granule with surrounding lymphocytic infiltrate

INHALED EPOPROSTENOL AS SOLO OR ADJUNCTIVE THERAPY FOR PULMONARY ARTERY HYPERTENSION

Pulmonary arterial hypertension (PAH) is a common finding in patients with significant valvular heart disease. Post operative mortality is increased in these patients. Currently, the most commonly used drug to rapidly decrease pulmonary artery pressure is nitric oxide.Epoprostenol (EPO) is less expensive, less toxic, and easier to administer when compared to inhaled nitric oxide. Inhaled EPO may be an alternative to IV EPO, as it has selective pulmonary vasodilator properties and less systemic side effects. Hache, et al, studied the effect of inhaled EPO compared to a placebo in twenty patients undergoing cardiothoracic surgery and concluded it was safe. In our study, we treated patients with increased pulmonary artery pressure, undergoing cardiothoracic surgery, with inhaled EPO to determine efficacy.

Of all patients, seventy two (82.8%) underwent valve surgeries, seven (8.1%) had LVAD’s, and two (2.3%) had heart transplants. Inhaled EPO was used as adjuvant therapy in 6 (6.7%) medical patients. No adverse effects from this therapy was observed.Hemodynamic parameters are statistically significant. Population demographics are presented in the table.

2.92 +/- 0.7 (p<0.001)Cardiac Index (Post)

Number of Patients n=87

Average age 67 ( Range 31-88 )

sex M= 54 , F= 33

Heart Failure (EF < 40) 51 (58.6%)

Average days on Ventilator 5

Valve Disorders

Mitral Regurgitation (Total ) 54

Severe / Moderate / Mild 27 / 17 /10

Tricuspid Regurgitation (Total) 30

Severe / Moderate /Mild 17 / 9 / 4

Aortic Stenosis (Total) 14

Severe / Moderate 12 / 2

Aortic Regurgitation 10

Surgeries

Mitral valve Replacement 16

Mitral Valve Repair 28

Aortic Valve Replacement 21

Cardiac Index (Pre) (n=52) 2.12 +/- 0.5

PAP pre-op (Mean) (n=56) 39 +/- 0.52

PAP Post-op (Mean) 25.1 +/- 0.5 (p<0.001)

Average cost inhaled EPO $19/hour

Average cost inhaled NO $132/hour

Results

University of Wisconsin School of Medicine and Public Health-Milwaukee Clinical Campus

TREPROSTINIL (Tyvaso)TREPROSTINIL (Tyvaso)

►Prostaglandin – inhaled.Prostaglandin – inhaled.

►2-12 breaths / treatment qid2-12 breaths / treatment qid

►Same side effects as any Same side effects as any Prostaglandin during titrationProstaglandin during titration

TADALAFIL (AdcircaTADALAFIL (Adcirca))

► PDE-5 inhibitorPDE-5 inhibitor

► 20-40mg daily po20-40mg daily po

► 36 hour ½ life36 hour ½ life

► Avoid with Rifampin and AntifungalsAvoid with Rifampin and Antifungals

PERCUTANEOUS INTERVENTION IN PERCUTANEOUS INTERVENTION IN PULMONARY HYPERTENSIONPULMONARY HYPERTENSION

►Coil Closure of PDACoil Closure of PDA►ASD ClosureASD Closure►VSD ClosureVSD Closure►Atrial SeptostomyAtrial Septostomy

SURGICAL PROCEDURES IN SURGICAL PROCEDURES IN PULMONARY HYPERTENSIONPULMONARY HYPERTENSION

►ASD / VSD ClosureASD / VSD Closure►Mitral Valve Repair / ReplacementMitral Valve Repair / Replacement►Anomolous Pulmonary Venous ReturnAnomolous Pulmonary Venous Return►Pulmonary Thrombo-EndarterectomyPulmonary Thrombo-Endarterectomy►Open Lung BiopsyOpen Lung Biopsy►Pericardial Window / DrainagePericardial Window / Drainage

CURRENT CLINICAL TRIALSCURRENT CLINICAL TRIALS

- Oral Remodulin - (United Therapeutics)Oral Remodulin - (United Therapeutics)

- Selexipag - (Actileon)Selexipag - (Actileon)

- Combo Study vs single drug - Adcirca +/-Letairis (United Therapeutics / Gilead)Combo Study vs single drug - Adcirca +/-Letairis (United Therapeutics / Gilead)

- Riociguat with LV Failure and PHTN - (Bayer)Riociguat with LV Failure and PHTN - (Bayer)

- Tyvaso Registry - (United Therapeutics)Tyvaso Registry - (United Therapeutics)

- Implantable pump / continuous infusion Remodulin - (Medtronics)Implantable pump / continuous infusion Remodulin - (Medtronics)

- Inhaled nitric oxide - (GENO)Inhaled nitric oxide - (GENO)

-- Inhaled Nitric Oxide via Ambulatory Device (Ikaria)Inhaled Nitric Oxide via Ambulatory Device (Ikaria)

- Taladafil with LV Failure and PHTN (NIH)Taladafil with LV Failure and PHTN (NIH)

- Oral Beraprost (LungRx)Oral Beraprost (LungRx)

▪ Prostacyclins

▪ Nitric Oxide

▪ PD’s

▪ ERA

▪ Combo

CASESCASES

48 y/o female PAH / ICM48 y/o female PAH / ICM

► CREST syndrome x 6 yearsCREST syndrome x 6 years

► Anterior wall MI Anterior wall MI → LVEF 15-20%→ LVEF 15-20%

► PAH – RA-18, RV-86/22, PA-88/22 (55), W-PAH – RA-18, RV-86/22, PA-88/22 (55), W-16, CI-1.8, PA-Sat 48%, Ao-92%, PVR-12.18 16, CI-1.8, PA-Sat 48%, Ao-92%, PVR-12.18 WUWU

► IV Remodulin titrated to 100ng/kg/minIV Remodulin titrated to 100ng/kg/min

► Ambrisentan 5Ambrisentan 5→10mg po daily→10mg po daily

► Digoxin 0.25mg dailyDigoxin 0.25mg daily

48 y/o female PAH / ICM – 48 y/o female PAH / ICM – (continued)(continued)

► Lasix 40mg dailyLasix 40mg daily► K/Mg replacementK/Mg replacement► Lisinopril 20mg daily / DC CoregLisinopril 20mg daily / DC Coreg► More Aggressive immunosuppressionMore Aggressive immunosuppression______________________________________________________________________________________

** LVAD – Heartmate II for 6-7 monthsLVAD – Heartmate II for 6-7 months** Successfully transplanted (heart)Successfully transplanted (heart)** Weaned off RemodulinWeaned off Remodulin

42 y/o male - Hep C ETOH Liver Dz42 y/o male - Hep C ETOH Liver Dz

► Massive ascites, LE edema, severe RH Massive ascites, LE edema, severe RH failurefailure

► Normal LV, no significant valve diseaseNormal LV, no significant valve disease

► Right Heart Cath….Right Heart Cath….Hepatic wedge - 18Hepatic wedge - 18 CI – 1.9CI – 1.9RA – 18RA – 18 PVR – 9 WUPVR – 9 WURV – 19 / 22RV – 19 / 22PA – 92 / 25 (54)PA – 92 / 25 (54)

42 y/o male - Hep C ETOH Liver Dz 42 y/o male - Hep C ETOH Liver Dz (continued)(continued)

► IV Lasix, Dobutamine, FlolanIV Lasix, Dobutamine, Flolan► Digoxin 0.25mg daily, K/Mg replacementDigoxin 0.25mg daily, K/Mg replacement► Flolan changed to Veletri for home infusionFlolan changed to Veletri for home infusion► Revatio 20mg tid added Revatio 20mg tid added ________________________________________________________________________________________________

► Liver transplant after PVR Liver transplant after PVR ↓ to 5 WU, CI >2.8↓ to 5 WU, CI >2.8► ECHO =ECHO = marked improvement of RVEFmarked improvement of RVEF ________________________________________________________________________________________________

** 3 months after transplant – weaned off IV Veletri3 months after transplant – weaned off IV Veletri** 9 months after transplant – weaned from Revatio9 months after transplant – weaned from Revatio** Stable 1 year after cessation of all PAH drugsStable 1 year after cessation of all PAH drugs

69 y/o old female - HCM69 y/o old female - HCM

► NYHA 3, 3+ edema to mid thighs, + ascitesNYHA 3, 3+ edema to mid thighs, + ascites

► Severe DOE and muscle wastingSevere DOE and muscle wasting

► ECHO – mild RVH, mod LVH, RVSP 55, LVEF 65%ECHO – mild RVH, mod LVH, RVSP 55, LVEF 65%

► PHTN work up – negativePHTN work up – negative

► Cath – RA-18, RV-58/19, PA-55/22, CI-2.8, W-20, PA-Sat Cath – RA-18, RV-58/19, PA-55/22, CI-2.8, W-20, PA-Sat 55%, PVR-3.2 WU, 55%, PVR-3.2 WU,

► Treatment – IV Lasix Treatment – IV Lasix → CVVH→ CVVH________________________________________________________________________________________________________________________________

** Home on peritoneal dialysis x 9 monthsHome on peritoneal dialysis x 9 months** Evaluate for transplant – status 7Evaluate for transplant – status 7

PAH – Pulmonary EmboliPAH – Pulmonary Emboli

56 year old female with PE after Hysterectomy56 year old female with PE after Hysterectomy

► Well until 3 years ago, 0Well until 3 years ago, 02 2 6L NC now6L NC now

► Denied PTE at another institutionDenied PTE at another institution► Reviewed Pulmonary AngiogramReviewed Pulmonary Angiogram► RHC – RA 8, RV RHC – RA 8, RV 6565//2020(35), CI 2.3, Sat-62%(35), CI 2.3, Sat-62%► Coronary AngiogramCoronary Angiogram► Sent to San DiegoSent to San Diego

Vague Symptoms

Major presenting symptoms are syncope, shortness of breath and fatigue

Syncope is prodrome to death

Correct diagnosis must be established

Empiric vasodilator therapy is not recommended

Treatment options are frequently available if not seen at end stage