1. PH: Who Ya Gonna Call Pulm Consults
Lana Melendres
Pulm/CC Division
Pulm Htn Program Director
4/24/13

2. 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

3. 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

4. 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.

5. 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)

6. 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.

7. Case #5
47yo man with SOB that has been progressive for the past several months. Previously able to ride his bike 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.
PVOD:
CT findings with

8. 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.

9. 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.

10. Normal Cardiac Hemodynamics

11. 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
Genevea convention in 2003 the diagnostic classification was mPAP of >25, included exercise >30 and wedge of <15mmHg with some mention of PVR needing to be >2 or 3 Woods units. At the Dana point conference in 2008 this definition was altered for a variety of reasons. The first was that when reviewing 47 studies on normal patients PAP, at rest the mean was but with exercise there was a wide range especially respective to age (>50 could be as high as 47). Currently, it is felt that mPAP of 8-20 is normal; is a gray zone with insufficient evidence; 25 or greater was PH.
Plexogenic arteriopathy (the parent muscular artery shows medial and intimal thickening) due to inflammatory process from cytokines and chemokines undergoes shear stress which results in damage causing transmural destruction that is repaired by grnaulation tissue= plexiform lesion.
Pleciform lesion= granulation tissue resulting from the parent muscular artery sustaining medial and intimal thickening that combined with shear stress at branch points
Gaine et al. The Lancet, 1998.

12. New Proposed Classification of Pulmonary Hypertension (Dana Point, 2008)
1. Pulmonary Arterial Hypertension 1.1 Idiopathic PAH 1.2 Heritable BMPR ALK1, endoglin (with or without hereditary hemorrhagic telangiectasia ) Unknown. 1.3 Drug- and toxin-induced 1.4 Associated with Connective tissue diseases HIV infection Portal hypertension Congenital heart diseases Schistosomiasis Chronic hemolytic anemia 1.5 Persistent pulmonary hypertension of the newborn 1’. Pulmonary veno-occlusive disease (PVO) and/or pulmonary capillary hemangiomatosis (PCH) 2. Pulmonary hypertension due to left heart disease 2.1 Systolic dysfunction 2.2 Diastolic dysfunction 2.3 Valvular disease
3. Pulmonary hypertension due to lung diseases and/or hypoxia
Chronic obstructive pulmonary disease
Interstitial lung disease
Other pulmonary diseases with mixed restrictive and obstructive pattern
Sleep-disordered breathing
Alveolar hypoventilation disorders
Chronic exposure to high altitude
Developmental abnormalities
4. Chronic thromboembolic pulmonary hypertension (CTEPH)
5. PH with unclear multifactorial mechanisms
Hematologic disorders: myeloproliferative disorders splenectomy.
Systemic disorders, sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis
Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders
Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis.

13. 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.

14. Pulmonary Arterial Hypertension
Case #1: IPAH
Case #2: PAH associated with HIV

15. PAH
Case #3: PAH assoc with drugs/toxins
Case #4: PAH assoc with CTD

16. PAH Case #5: PVOD Case #6: PAH assoc with CHD
Case #7: PAH assoc with portal htn

17. When to Call Pulmonary Definite Consult: Consider 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

18. Pulmonary Arterial Hypertension: Detection and Diagnosis
Is there a reason to suspect PAH
Clinical history (symptoms, risk factors, family Hs.),
Exam, CXR, ECG
yes no
Is PAH likely?
Echo
Rationale
TRV to measure RVSP; RVE; RAE; RV Dysfunction:
No further
evaluation
for PAH no
yes
Is PAH due to LH disease?
Echo
yes
Dx LV systolic, diastolic dysfunction; valvular disease:
Appropriate treatment and further evaluation
if necessary, including R&LHC no
Dx abnormal morphology; shunt:
Surgery. Medical treatment of PAH or evaluation for
further definition or other contributing causes,
including R&LHC if necessary
Is PAH due to CHD?
Echo with contrast
yes no
This detection and diagnosis algorithm was published in a recent Chest supplement focused on diagnosis and treatment of pulmonary hypertension. It provides a rigorous strategy to diagnose PH, and determine it’s cause which is key to determining the appropriate treatment approach. In some cases, medical history and/or the presence of risk factors will afford a re-order of this approach to initially hone in on and either confirm or eliminate the suspected cause.
Dx Scleroderma, SLE, other CTD, HIV: Medical
treatment of PAH and further evaluation for
other contributing causes, including RHC
Is PAH due to CTD, HIV?
Serologies
yes no
Is chronic PE suspected?
VQ scan
McGoon et al. Chest 2004;126:14S-34S

19. Pulmonary Arterial Hypertension: Detection and Diagnosis
Is chronic PE suspected?
VQ scan
yes
Is chronic PE confirmed and operable?
Pulmonary angiogram
yes no
VQ normal
Anatomic definition (CT, MRI may provide additional useful
but not definitive information):
Thromboendarterectomy if appropriate or medical
treatment; clotting evaluation; a/c
Is PAH due to lung disease
or hypoxemia?
PFTs, arterial saturation no
yes
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 no
Document exercise capacity regardless of cause of PH:
Establish baseline, prognosis and document progression/
response to treatment with serial reassessments
What limitations are caused by
the PAH?
Functional class; 6-minute walk
test
..... The final step in diagnosing PAH is right heart catheterization
Document PA and RA pressures, PCWP (LV or LA pressure
if 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 are the precise pulmonary
hemodynamics?
RHC
McGoon et al. Chest 2004;126:14S-34S

20. NYHA Classification

21. 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
Right heart catheterization is the diagnostic gold standard. This evaluation is necessary to sufficiently rule out secondary causes of disease and left sided heart disease. This evaluation is also necessary to obtain the critical measures of cardiac index and calculated PVR which have significant value prognostically.
RHC can also Prognosticate!
Rich et al. WHO Symposium on PPH. Evian, France,1998.

22. Determinants of Disease Severity
Determinants of risk
Lower risk
Higher risk
Clinical 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:

23. Therapeutic Pathways

24. 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.

25. Therapeutic Options for PAH
Traditional therapies
FDA approved for PAH
Supplemental O2
Diuretics
Oral vasodilators
(CCB)
Anticoagulants
warfarin
Inotropic agents
Digitalis
Prostanoids
Epoprostenol (flolan/veletri)
Treprostinil (IV/SQ/Inhaled)
Inhaled Iloprost
ERA’s
Bosentan
Ambrisentan
PDE-5 Inhibitors
Sildenafil
Tadalafil

26. Natural History of PAH: NIH Registry1,2
69%
56%
46%
Percent survival
38%
Predicted survival
Predicted survival*
Years
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: D’Alonzo et al. Ann Intern Med. 1991;115:

27. 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

28. Questions?