PH: Who Ya Gonna CallPulm Consults

Lana MelendresPulm/CC Division

Pulm Htn Program Director4/24/13

Objectives

• Define pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH)

• Identify the 5 different groups of PH• When to call a lifeline (pulm consult)• Review the workup for PH• Making the diagnosis• Therapeutic options

Case #1

• 35yo woman with PMHx significant for exercise induced asthma and anxiety presenting to the ED after “syncope”.

• Remembers trying to pick up her 2 year old daughter when the “curtains closed” and she “went down”

• SOB worsening despite use of inhalers

Case #2

• 29yo man with HIV presenting to the ED with 2 month h/o of worsening SOB on exertion that has dramatically worsened over the past week to the point that he is now having SOB at rest and feeling dizzy when standing not on any medications.

• Recently moved from California and has no information in our system.

Case #3

• 46yo morbidly obese woman with DM, htn, and presumed OSA/OHS presenting to the ED with fatigue and worsening lower ext edema.

• Recently established with a PCP and started on therapies for her DM, htn and was referred for a sleep study (will be seen in Oct 2013)

Case #4

• 65yo woman with little PMHx presenting with SOB and exhaustion. Has no medical problems that she knows of, just retired from teaching for the past 40years.

• Previously playing 18 holes of golf, now only able to walk 15ft before needing to stop and rest.

Case #5

• 47yo man with SOB that has been progressive for the past several months. Previously able to ride his bike 100-150 miles a week, now to sob to ride more than 5-10 miles at a time.

• No medical problems that he is aware of. Works as a nuclear engineer. Takes no medication.

• CT scan showed nodules, lymphadenopathy, and septal thickening.

Case #6

• 83yo woman has been healthy her whole life now presenting with worsening fatigue with exertion.

• Previously able to swim for 30 minutes a day and walk for 30min, now sob with much less. Unable to keep up with her friend.

• Experiencing palpitations and chest pressure intermittently.

Case #7

• 52yo man with ESRD on HD, htn, DM, CAD, cirrhosis from hep C and prior ETOH abuse and mild COPD, no longer smoking, admitted after missing two HD appointments with profound fluid overload.

• Also notes that he has had worsening SOB over the past year and fluid retention.

Normal Cardiac Hemodynamics

Diagnostic Definition: Pulmonary Hypertension

Rest:- Mean PAP >25 mmHg

PAH = above + PCWP or LVEDP <15 mmHg

Associated with adverse changes- In the pulmonary vasculature (arteriopathy)- At the level of the right ventricle (hypertrophy)

No longer part of the definition:Exercise:

- Mean PAP > 30 mmHg

Gaine et al. The Lancet, 1998.

New Proposed Classification of Pulmonary Hypertension

(Dana Point, 2008)1. Pulmonary Arterial Hypertension 1.1 Idiopathic PAH1.2 Heritable

1.2.1. BMPR21.2.2. ALK1, endoglin (with or without hereditary

hemorrhagic telangiectasia )1.2.3 Unknown.

1.3 Drug- and toxin-induced1.4 Associated with

1.4.1. Connective tissue diseases1.4.2 HIV infection1.4.3 Portal hypertension1.4.4 Congenital heart diseases1.4.5 Schistosomiasis1.4.6 Chronic hemolytic anemia

1.5 Persistent pulmonary hypertension of the newborn1’. Pulmonary veno-occlusive disease (PVO)

and/or pulmonary capillary hemangiomatosis (PCH)

2. Pulmonary hypertension due to left heart disease

2.1 Systolic dysfunction2.2 Diastolic dysfunction2.3 Valvular disease

3. Pulmonary hypertension due to lung diseases and/or hypoxia3.1 Chronic obstructive pulmonary disease3.2 Interstitial lung disease3.3 Other pulmonary diseases with mixed restrictive and obstructive pattern3.4 Sleep-disordered breathing3.5 Alveolar hypoventilation disorders3.6 Chronic exposure to high altitude3.7 Developmental abnormalities

4. Chronic thromboembolic pulmonary hypertension (CTEPH)

5. PH with unclear multifactorial mechanisms5.1 Hematologic disorders: myeloproliferative disorders splenectomy.5.2 Systemic disorders, sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis5.3 Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders 5.4 Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis.

Back to the Cases

• What do all the patients presented have in common? – Each patient was found to have pulmonary arterial

hypertension after full w/u and diagnosis by right heart catheterization.

Pulmonary Arterial Hypertension

• Case #1: IPAH

• Case #2: PAH associated with HIV

PAH

• Case #3: PAH assoc with drugs/toxins

• Case #4: PAH assoc with CTD

PAH

• Case #5: PVOD

• Case #6: PAH assoc with CHD

• Case #7: PAH assoc with portal htn

When to Call Pulmonary

• Definite Consult:– Patient with known PAH by RHC, on PAH specific

therapies– All patients followed by the PH clinic.

• Consider Consult:– Patient with echo findings of elevated PASP:• No known CTD, PASP >40mmHg• Known CTD, PASP >35mmHg

McGoon et al. Chest 2004;126:14S-34S

No furtherevaluation

for PAH

Is PAH likely?Echo

Is there a reason to suspect PAHClinical history (symptoms, risk factors, family Hs.),

Exam, CXR, ECG

Is PAH due to LH disease?Echo

Is PAH due to CHD?Echo with contrast

Is PAH due to CTD, HIV?Serologies

Dx Scleroderma, SLE, other CTD, HIV: Medicaltreatment of PAH and further evaluation for

other contributing causes, including RHC

Dx abnormal morphology; shunt:Surgery. Medical treatment of PAH or evaluation for

further definition or other contributing causes, including R&LHC if necessary

Dx LV systolic, diastolic dysfunction; valvular disease:Appropriate treatment and further evaluation

if necessary, including R&LHC

TRV to measure RVSP; RVE; RAE; RV Dysfunction:

yes

yes

yes

Rationale

no

no

no

yes

yesno

no

Pulmonary Arterial Hypertension: Detection and Diagnosis

Is chronic PE suspected?VQ scan

McGoon et al. Chest 2004;126:14S-34S

Dx parenchymal lung disease, hypoxemia, or sleep disorder: Medical treatment, oxygen, positive pressure breathing

as appropriate, and further evaluation for other contributing causes, including RHC if necessary

yes

Document exercise capacity regardless of cause of PH: Establish baseline, prognosis and document progression/

response to treatment with serial reassessments

Document PA and RA pressures, PCWP (LV or LA pressureif PCWP unobtainable or uncertain), transpulmonary gradient

CO, PVR, SvO2, response to vasodilators: Confirm PAH, or IPAH if no other cause identified

Discuss genetic testing and counseling of IPAH

What limitations are caused bythe PAH?

Functional class; 6-minute walktest

What are the precise pulmonaryhemodynamics?

RHC

Is chronic PE suspected?VQ scan

Is PAH due to lung diseaseor hypoxemia?

PFTs, arterial saturation

Is chronic PE confirmed and operable?Pulmonary angiogram

Anatomic definition (CT, MRI may provide additional useful but not definitive information):

Thromboendarterectomy if appropriate or medical treatment; clotting evaluation; a/c

yesyes

no

no

no VQ normal

Pulmonary Arterial Hypertension: Detection and Diagnosis

NYHA Classification

Right Heart Catheterization is the Diagnostic Gold Standard

• Saturations– Rule Out Shunts

• Intra-cardiac• Intra-Pulmonary

• Hemodynamics– RAP– mPAP– PCWP

• Rule out left sided heart disease– CO/CI– PVR

• Angiography– Vessel properties– CTEPH

• Vasodilator Response

Rich et al. WHO Symposium on PPH. Evian, France,1998.

RHC can also Prognosticate!

Determinants of Disease Severity

Determinants of risk Lower risk Higher riskClinical evidence of RV failure No Yes

Progression Gradual Rapid

WHO functional class II, III IV

6MWD Longer (>400 m) Shorter (<300 m)

BNP Minimally elevated Very elevated

Echocardiographic findings Minimal RV dysfunction Significant RV dysfunction, pericardial effusion

Hemodynamics Normal/near normal RAP and CI

High RAP, low CI

BNP = brain natriuretic peptide; CI = cardiac index; RAP = right artery pressure; RV = right ventricular.

McLaughlin and McGoon. Circulation. 2006;114:1417-1431.

Therapeutic Pathways

Therapies

• The only group that has been approved for the specialized medications for pulmonary hypertension are Group 1 (pulmonary arterial hypertension/PAH)

• The other groups require treatment of the underlying condition causing the elevated pressures.

Therapeutic Options for PAH

Traditional therapies

• Supplemental O2

• Diuretics• Oral vasodilators– (CCB)

• Anticoagulants– warfarin

• Inotropic agents– Digitalis

FDA approved for PAH

• Prostanoids– Epoprostenol (flolan/veletri)– Treprostinil (IV/SQ/Inhaled)– Inhaled Iloprost

• ERA’s– Bosentan– Ambrisentan

• PDE-5 Inhibitors– Sildenafil– Tadalafil

Natural History of PAH: NIH Registry1,2

NIH = National Institutes of Health.Predicted survival according to the NIH equation. Predicted survival rates were 69%, 56%, 46%, and 38% at 1, 2, 3, and 4 years, respectively. The numbers of patients at risk were 231, 149, 82, and 10 at 1, 2, 3, and 4 years, respectively. *Patients with primary pulmonary hypertension, now referred to as idiopathic pulmonary hypertension.

1. Rich et al. Ann Intern Med. 1987;107:216-223. 2. D’Alonzo et al. Ann Intern Med. 1991;115:343-349.

Predicted survival*

69%

56%

46%

38%

Predicted survivalPerc

ent s

urvi

val

Years

The Take Home

• Most crucial aspect: the patient’s history• If concerned about PAH or have PAH, call the

pulm consult service to help in management• Timing of RHC is essential• If on PAH specific therapy, Do Not Abruptly

Stop

Questions?