Terry Fortin, MD Duke University

1. Pulmonary
Hypertension
Basics 2023
NOVEMBER 17, 2023
DUKE PULMONARY
VASCULAR DISEASE
CENTER
Terry Fortin MD
Associate Professor of Medicine
Division of Cardiology
Duke University Hospital

2. Agenda
• What is Pulmonary Hypertension and Pulmonary Arterial Hypertension
• Basic Physiology ( How does it work)
• Classification- Groups of PH
• Updates since 2018
• Guidance
• Proceedings of the 6th World Symposium of Pulmonary HTN 2018
Name MRN

3. Pulmonary Hypertension (PH) vs. Pulmonary Arterial
Hypertension (PAH)
• Pulmonary hypertension: Elevated pulmonary pressure on an
echo or Right Heart Cath with multiple potential etiologies.
Not specific as to whether this is a pre or post capillary or flow
mediated. ( high blood pressure in lungs but need more info)
Pulmonary arterial hypertension (PAH) results from restricted
flow through pulmonary arterial circulation. Specific disease of
the tiny blood vessels in the lungs. Extra cells and narrow.
– Leads to  pulmonary vascular resistance (PVR), then over time
causes right heart failure
– Predominant cause – loss of vascular luminal volume from vascular
remodeling, excessive cell proliferation, ↓ apoptosis. Overall less
area in the blood vessels
McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the
American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed
in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension
Association. J Am Coll Cardiol. 2009;53:1573-1619.

4. Pulmonary Arterial Hypertension PAH
• Pulmonary arterial hypertension
(PAH) is a progressive, incurable
disease of the small pulmonary
arteries characterized by vascular cell
proliferation, aberrant remodeling,
and thrombosis in situ.
• Degree of vascular constriction varies
1. Farber HW, et al. N Engl J Med. 2004;351:1655-1665.

5. Rajan Saggar med Ed on the go. How are CTD and
PAH related
Pulmonary Hypertension (PH)

6. • Mean PAP > 20 mmHg
1
• Wedge < 15 mmHg
2
• PVR > 2 WU (160 dynes)
3
Definition of PAH: Clinical, Hemodynamic
6th World Symposium 2018
6th World Symposium on PH 2018

7. Precapillary arteriolar
discontinuity

8. PAH: RV Changes
Normal PH
RA
LA
RV
LV
TTE apical
4-chamber view

9. 1.1 Idiopathic PAH
1.2 PAH with vasoreactivity (Table 1)
1.3 Heritable PAH (Table 2)
1.4 Drugs and toxins induced (Table 3)
1.5 Associated with:
1.5.1 Connective tissue disease
1.5.2 HIV infection
1.5.3 Portal hypertension
1.5.4 Congenital heart disease (Table 4)
1.5.5 Schistosomiasis
1.6 PAH with overt signs of venous/capillaries
(PVOD/PCH) involvement (Table 5)
1.7 Persistent PH of the Newborn syndrome (Table P1)
1. Pulmonary Arterial Hypertension
2.1 PH due to heart failure with preserved E.F
2.2 PH due to heart failure with reduced E.F
2.3 Valvular heart disease
2.4 Congenital post-capillary obstructive lesions (Table
P2)
2. PH due to left heart disease
3.1 Obstructive lung disease
3.2 Restrictive lung disease
3.3 Other lung disease with mixed restrictive/obstructive
pattern
3.4 Hypoxia without lung disease
3.5 Developmental lung disorders (Table P3)
3. PH due to lung diseases and/or hypoxia (Table 6)
4.1 Chronic thromboembolic PH
4.2 Other pulmonary artery obstructions (Table 7)
4. PH due to pulmonary artery obstruction
5.1 Haematologic disorders
5.2 Systemic disorders
5.3 Others
5.4 Complex congenital heart disease (Table P4)
5. PH with unclear mechanisms (Table 8)
WSPH 2018: New Clinical Classification of PH

10. Echocardiogram
PFTs
Polysomnography
VQ Scan
• Sleep Disorder
• Chronic PE
Functional Test
(6MWT, CPET)
Overnight Oximetry
History
Exam
CXR
ECG
HIV
ANA
LFTs
RH Cath
TEE
Exercise Echo
Pulmonary Angiography
Chest CT Angiogram
Coagulopathy Profile
Vasodilator Test
Exercise RH Cath
Volume Loading
ABGs
• Index of Suspicion of PH
• RVE, RAE, RVSP, RV Function
• Left Heart Disease
• VHD, CHD
• Ventilatory Function
• Gas Exchange
Other CTD Serologies
• HIV Infection
• Scleroderma, SLE, RA
• Portopulmonary Htn
• Establish Baseline
• Prognosis
• Confirmation of PH
• Hemodynamic Profile
• Vasodilator Response
Pivotal Tests Contingent Tests Contribute to Assessment
of:
Left Heart Cath
McLaughlin VV et al. J Am Coll Cardiol.
2009;53:1573-1619.
Current
ACCF/AHA
Diagnostic
Algorithm

11. Not All PH is the Same

12. McLaughlin VV and McGoon M. In press.
Lower Risk Determinants of Risk Higher Risk
No
Clinical evidence of
RV failure
Yes
Gradual Progression Rapid
II, III WHO class IV
Longer (>400 m) 6MW distance Shorter (<300 m)
Minimally elevated BNP Very elevated
Minimal RV
dysfunction
Echocardiographic
findings
Pericardial effusion,
significant RV
dysfunction
Normal/near normal
RAP and CI
Hemodynamics High RAP, low CI

13. PAH Treatment Algorithm (WSPH 2018)
Galié N, Channick RN, Frantz RP, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J 2018; in press [https://doi.org/10.1183/13993003.01889-
2018].
PAH Confirmed
by Expert
Center
Non-Vasoreactive
High Risk
(WHO FC IV)
Vasoreactive
After 3-6 Months of Treatment
Consider
Referral For
Lung
Transplantatio
n
Maximal Medical
Therapy and Listing
for Lung
Transplantation
Potential Role For Initial
Monotherapy
Treatment-
Naïve Patient
Patient Already
On Treatment
CCB Therapy
Acute Vasoreactivity Test
(IPAH/hPAH/DPAH Only)
Initial Oral
Combination
Initial Combination
Including IV PCA
Add On Therapy
(Double/Triple)
General Measures
Supportive Therapy
Intermediate Risk High Risk
Intermediate Risk High Risk
Intermediate Risk
Low Risk
Low Risk
Structured Follow-
Up
After 3-6 Months of Treatment

14. PAH-Specific, FDA-Approved Therapies for Use in the US
Endothelin Receptor
Antagonists
NO-cGMP Pathway
Prostanoids –
Prostacyclin Analogs
Prostacyclin Agonists
Bosentan (PO)
(Tracleer®)
FDA Approved: 2001
Sildenafil (PO)
(Revatio®)
FDA Approved: June 2005
Epoprostenol (IV)
(Flolan® or Veletri®)
Flolan FDA Approved: September 1995
Veletri FDA Approved: June 2008
Selexipag (PO)
(Uptravi®)
FDA Approved: December 2015
Ambrisentan (PO)
(Letairis®)
FDA Approved: June 2007
Tadalafil (PO)
(Adcirca®)
FDA Approved: May 2009
Treprostinil (IV, SC, PO, and
inhaled)
(Remodulin®, Tyvaso®, Orenitram®)
First (SC formulation) FDA Approved:
July 2002
Macitentan (PO)
(Opsumit®)
FDA Approved: October 2013
Riociguat (PO)
(Adempas®)
FDA Approved: October 2013
Iloprost (inhaled)
(Ventavis®)
FDA Approved: December 2004
http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Search_Drug_Name. Accessed April 1, 2016.